Journal of Clinical Medicine

Open AccessEditor’s ChoiceArticle

Median Nerve Stimulation for Treatment of Tics: Randomized, Controlled, Crossover Trial

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J. Clin. Med. 2023, 12(7), 2514; https://doi.org/10.3390/jcm12072514 - 27 Mar 2023

Cited by 2 | Viewed by 856

Abstract

A prior study showed that rhythmic, but not arrhythmic, 12 Hz stimulation of the median nerve (MNS) entrained the sensorimotor cortex EEG signal and found that 10 Hz MNS improved tics in Tourette syndrome (TS). However, no control condition was tested, and stimulation [...] Read more.

A prior study showed that rhythmic, but not arrhythmic, 12 Hz stimulation of the median nerve (MNS) entrained the sensorimotor cortex EEG signal and found that 10 Hz MNS improved tics in Tourette syndrome (TS). However, no control condition was tested, and stimulation blocks lasted only 1 min. We set out to replicate the TS results and to test whether tic improvement occurs by the proposed cortical entrainment mechanism. Preregistration was completed at ClinicalTrials.gov, under number NCT04731714. Thirty-two people with TS, age 15–64, completed two study visits with repeated MNS on and off blocks in random order, one visit for rhythmic and one for arrhythmic MNS. Subjects and staff were blind to order; a video rater was additionally blind to stimulation and to the order of visits and blocks. Rhythmic MNS at 10 Hz improved tics. Both rhythmic and arrhythmic 12 Hz MNS improved tic frequency, intensity, and urges, but the two treatments did not differ significantly. Participant masking was effective, and there was no carryover effect. Several participants described a dramatic benefit. Discomfort was minimal. There was no evidence that the MNS benefit persisted after stimulation ended. These results replicate the tic benefit from MNS but show that the EEG entrainment hypothesis cannot explain that benefit. Another electrophysiological mechanism may explain the benefit; alternatively, these data do not exclude a placebo effect. Full article

(This article belongs to the Section Mental Health)

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Open AccessEditor’s ChoiceReview

Alliance for Sleep Clinical Practice Guideline on Switching or Deprescribing Hypnotic Medications for Insomnia

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J. Clin. Med. 2023, 12(7), 2493; https://doi.org/10.3390/jcm12072493 - 25 Mar 2023

Cited by 1 | Viewed by 6770

Abstract

Determining the most effective insomnia medication for patients may require therapeutic trials of different medications. In addition, medication side effects, interactions with co-administered medications, and declining therapeutic efficacy can necessitate switching between different insomnia medications or deprescribing altogether. Currently, little guidance exists regarding [...] Read more.

Determining the most effective insomnia medication for patients may require therapeutic trials of different medications. In addition, medication side effects, interactions with co-administered medications, and declining therapeutic efficacy can necessitate switching between different insomnia medications or deprescribing altogether. Currently, little guidance exists regarding the safest and most effective way to transition from one medication to another. Thus, we developed evidence-based guidelines to inform clinicians regarding best practices when deprescribing or transitioning between insomnia medications. Five U.S.-based sleep experts reviewed the literature involving insomnia medication deprescribing, tapering, and switching and rated the quality of evidence. They used this evidence to generate recommendations through discussion and consensus. When switching or discontinuing insomnia medications, we recommend benzodiazepine hypnotic drugs be tapered while additional CBT-I is provided. For Z-drugs zolpidem and eszopiclone (and not zaleplon), especially when prescribed at supratherapeutic doses, tapering is recommended with a 1–2-day delay in administration of the next insomnia therapy when applicable. There is no need to taper DORAs, doxepin, and ramelteon. Lastly, off-label antidepressants and antipsychotics used to treat insomnia should be gradually reduced when discontinuing. In general, offering individuals a rationale for deprescribing or switching and involving them in the decision-making process can facilitate the change and enhance treatment success. Full article

(This article belongs to the Special Issue Insomnia Treatments: New Perspectives)

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Open AccessEditor’s ChoiceCase Report

Hypereosinophilic Syndrome Following the BNT162b2 (BioNTech/Pfizer) Vaccine Successfully Treated with Mepolizumab: A Case Report and Review of the Literature

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Ariela Hoxha

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Tania Tomaselli

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Giacomo Maria Minicucci

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J. Clin. Med. 2023, 12(6), 2376; https://doi.org/10.3390/jcm12062376 - 19 Mar 2023

Viewed by 1650

Abstract

Although an increasing number of real-life data confirm large-scale clinical trial findings on the efficacy and safety of SARS-CoV-2 vaccines, rare but severe adverse reactions have begun to emerge. Here, we report a full-blown hypereosinophilic syndrome (HES) following a BNT162b2 (BioNTech/Pfizer) vaccine. A [...] Read more.

Although an increasing number of real-life data confirm large-scale clinical trial findings on the efficacy and safety of SARS-CoV-2 vaccines, rare but severe adverse reactions have begun to emerge. Here, we report a full-blown hypereosinophilic syndrome (HES) following a BNT162b2 (BioNTech/Pfizer) vaccine. A 48-year-old man developed, 5 days after the first shot of the SARS-CoV-2 vaccine, erythematous and painful nodular lesions in the lower and upper limbs accompanied by widespread itching, acrocyanosis with gangrenous lesions at the tips of the first and fourth fingers of the right hand, as well as paresthesia in the right hand and foot. Investigations revealed isolated eosinophilia, occlusion of the right ulnar artery, and electromyography alteration compatible with multifocal sensory neuropathy, as well as minimal accentuation of the interstitial texture with some ground glass appearance. Despite treatment with prednisone in combination with warfarin, he developed thrombosis of the left ulnar artery. Therefore, therapy with an IL-5 inhibitor and acetylsalicylic was successfully added. Given the time interval between the onset of clinical manifestations and the vaccine shot, we believe that the mRNA vaccine triggered the eosinophilic response. This case evidences a possible link between HES and the SARS-CoV-2 vaccination. Mepolizumab, an IL-5 inhibitor, might be considered in steroid refractory cases. Full article

(This article belongs to the Section Immunology)

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Open AccessEditor’s ChoiceReview

The Biology of Stress Intolerance in Patients with Chronic Pain—State of the Art and Future Directions

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J. Clin. Med. 2023, 12(6), 2245; https://doi.org/10.3390/jcm12062245 - 14 Mar 2023

Cited by 1 | Viewed by 2800

Abstract

Stress has been consistently linked to negative impacts on physical and mental health. More specifically, patients with chronic pain experience stress intolerance, which is an exacerbation or occurrence of symptoms in response to any type of stress. The pathophysiological mechanisms underlying this phenomenon [...] Read more.

Stress has been consistently linked to negative impacts on physical and mental health. More specifically, patients with chronic pain experience stress intolerance, which is an exacerbation or occurrence of symptoms in response to any type of stress. The pathophysiological mechanisms underlying this phenomenon remain unsolved. In this state-of-the-art paper, we summarised the role of the autonomic nervous system (ANS) and hypothalamus-pituitary-adrenal (HPA) axis, the two major stress response systems in stress intolerance. We provided insights into such mechanisms based on evidence from clinical studies in both patients with chronic pain, showing dysregulated stress systems, and healthy controls supported by preclinical studies, highlighting the link between these systems and symptoms of stress intolerance. Furthermore, we explored the possible regulating role for (epi)genetic mechanisms influencing the ANS and HPA axis. The link between stress and chronic pain has become an important area of research as it has the potential to inform the development of interventions to improve the quality of life for individuals living with chronic pain. As stress has become a prevalent concern in modern society, understanding the connection between stress, HPA axis, ANS, and chronic health conditions such as chronic pain is crucial to improve public health and well-being. Full article

(This article belongs to the Special Issue The Biology of Chronic Pain: Applications in Clinical Practice)

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Open AccessEditor’s ChoiceReview

Inferior Vena Cava Ultrasonography for Volume Status Evaluation: An Intriguing Promise Never Fulfilled

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J. Clin. Med. 2023, 12(6), 2217; https://doi.org/10.3390/jcm12062217 - 13 Mar 2023

Viewed by 6542

Abstract

The correct determination of volume status is a fundamental component of clinical evaluation as both hypovolaemia (with hypoperfusion) and hypervolaemia (with fluid overload) increase morbidity and mortality in critically ill patients. As inferior vena cava (IVC) accounts for two-thirds of systemic venous return, [...] Read more.

The correct determination of volume status is a fundamental component of clinical evaluation as both hypovolaemia (with hypoperfusion) and hypervolaemia (with fluid overload) increase morbidity and mortality in critically ill patients. As inferior vena cava (IVC) accounts for two-thirds of systemic venous return, it has been proposed as a marker of volaemic status by indirect assessment of central venous pressure or fluid responsiveness. Although ultrasonographic evaluation of IVC is relatively easy to perform, correct interpretation of the results may not be that simple and multiple pitfalls hamper its wider application in the clinical setting. In the present review, the basic elements of the pathophysiology of IVC behaviour, potential applications and limitations of its evaluation are discussed. Full article

(This article belongs to the Special Issue Ultrasound in Anesthesiology and Critical Care Medicine: From Concept to Clinical Applications)

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Open AccessEditor’s ChoiceReview

Secondary Cardiovascular Prevention after Acute Coronary Syndrome: Emerging Risk Factors and Novel Therapeutic Targets

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Angelo Silverio

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Francesco Paolo Cancro

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Maria Giovanna Vassallo

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J. Clin. Med. 2023, 12(6), 2161; https://doi.org/10.3390/jcm12062161 - 10 Mar 2023

Cited by 1 | Viewed by 1459

Abstract

The control of cardiovascular risk factors, the promotion of a healthy lifestyle, and antithrombotic therapy are the cornerstones of secondary prevention after acute coronary syndrome (ACS). However, many patients have recurrent ischemic events despite the optimal control of traditional modifiable risk factors and [...] Read more.

The control of cardiovascular risk factors, the promotion of a healthy lifestyle, and antithrombotic therapy are the cornerstones of secondary prevention after acute coronary syndrome (ACS). However, many patients have recurrent ischemic events despite the optimal control of traditional modifiable risk factors and the use of tailored pharmacological therapy, including new-generation antiplatelet and lipid-lowering agents. This evidence emphasizes the importance of identifying novel risk factors and targets to optimize secondary preventive strategies. Lipoprotein(a) (Lp(a)) has emerged as an independent predictor of adverse events after ACS. New molecules such as anti-PCSK9 monoclonal antibodies, small interfering RNAs, and antisense oligonucleotides can reduce plasma Lp(a) levels and are associated with a long-term outcome benefit after the index event. The inflammatory stimulus and the inflammasome, pivotal elements in the development and progression of atherosclerosis, have been widely investigated in patients with coronary artery disease. More recently, randomized clinical trials including post-ACS patients treated with colchicine and monoclonal antibodies targeting cytokines yielded promising results in the reduction in major cardiovascular events after an ACS. Gut dysbiosis has also raised great interest for its potential pathophysiological role in cardiovascular disease. This evidence, albeit preliminary and needing confirmation by larger population-based studies, suggests the possibility of targeting the gut microbiome in particularly high-risk populations. The risk of recurrent ischemic events after ACS is related to the complex interaction between intrinsic predisposing factors and environmental triggers. The identification of novel risk factors and targets is fundamental to customizing patient clinical management with a precision medicine perspective. Full article

(This article belongs to the Special Issue 'Clinical Advances' in Treatment of Acute Coronary Syndrome: Drafting from Theory to Clinical Practice)

Open AccessEditor’s ChoiceArticle

Comparison between the Flapless Surgical Approach and a Novel Single Incision Access in Terms of Recovery Time and Comfort after Extraction of Impacted Inferior Third Molars: A Randomised, Blinded, Split-Mouth Controlled Clinical Trial

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J. Clin. Med. 2023, 12(5), 1995; https://doi.org/10.3390/jcm12051995 - 02 Mar 2023

Cited by 1 | Viewed by 851

Abstract

The recent attention to quality of life and oral health care procedures reflects a renewed ‘patient-based’ approach to dealing with non-life-threatening conditions. In the current study, we proposed a novel surgical approach to the extraction of impacted inferior third molars (iMs3) through a [...] Read more.

The recent attention to quality of life and oral health care procedures reflects a renewed ‘patient-based’ approach to dealing with non-life-threatening conditions. In the current study, we proposed a novel surgical approach to the extraction of impacted inferior third molars (iMs3) through a randomised, blinded, split-mouth controlled clinical trial following the CONSORT guidelines. The novel surgical procedure, hereinafter referred to as single incision access (SIA), will be compared with our previously described flapless surgical approach (FSA). The predictor variable was the novel SIA approach, involving access through a single incision without removal of soft tissue, on the impacted iMs3. The primary endpoint was the acceleration of the iMs3 extraction healing time. The secondary endpoints were the incidences of pain and oedema as well as gum health (pocket probing depth and attached gingiva). The study was carried out on 84 teeth of 42 patients with both iMs3 impacted. The cohort was composed of 42% Caucasian males and 58% Caucasian females, aged 23.8 ± 7.9 (17–49) years. We observed faster recovery/wound-healing on the SIA side (33.6 ± 4.3 days) than at the FSA side (42.1 ± 5.4 days; p < 0.05). The FSA approach confirmed the evidence previously detected concerning early post-surgery improvement in terms of attached gingiva and reduced oedema and pain, with respect to the traditional envelope flap. The novel SIA approach follows the early positive post-surgery FSA results. Full article

(This article belongs to the Special Issue Breakthroughs in Oral and Maxillofacial Surgery)

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Open AccessEditor’s ChoiceArticle

Increasing Number of Cases Due to Candida auris in North Italy, July 2019–December 2022

J. Clin. Med. 2023, 12(5), 1912; https://doi.org/10.3390/jcm12051912 - 28 Feb 2023

Cited by 2 | Viewed by 854

Abstract

Candida auris is an emerging fungus that represents a serious health threat globally. In Italy, the first case was detected in July 2019. Then, one case was reported to the Ministry of Health (MoH) on January 2020. Nine months later, a huge number [...] Read more.

Candida auris is an emerging fungus that represents a serious health threat globally. In Italy, the first case was detected in July 2019. Then, one case was reported to the Ministry of Health (MoH) on January 2020. Nine months later, a huge number of cases were reported in northern Italy. Overall, 361 cases were detected in 17 healthcare facilities between July 2019 and December 2022 in the Liguria, Piedmont, Emilia-Romagna, and Veneto regions, including 146 (40.4%) deaths. The majority of cases (91.8%) were considered as colonised. Only one had a history of travel abroad. Microbiological data on seven isolates showed that all but one strain (85.7%) were resistant to fluconazole. All the environmental samples tested negative. Weekly screening of contacts was performed by the healthcare facilities. Infection prevention and control (IPC) measures were applied locally. The MoH nominated a National Reference Laboratory to characterise C. auris isolates and store the strains. In 2021, Italy posted two messages through the Epidemic Intelligence Information System (EPIS) to inform on the cases. On February 2022, a rapid risk assessment indicated a high risk for further spread within Italy, but a low risk of spread to other countries. Full article

(This article belongs to the Section Epidemiology & Public Health)

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Open AccessEditor’s ChoiceReview

What’s New in the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD)

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Marcin Kosmalski

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Rafał Frankowski

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Sylwia Ziółkowska

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Monika Różycka-Kosmalska

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Tadeusz Pietras

J. Clin. Med. 2023, 12(5), 1852; https://doi.org/10.3390/jcm12051852 - 26 Feb 2023

Cited by 1 | Viewed by 3024

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a serious health problem due to its high incidence and consequences. In view of the existing controversies, new therapeutic options for NAFLD are still being sought. Therefore, the aim of our review was to evaluate the recently [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) is a serious health problem due to its high incidence and consequences. In view of the existing controversies, new therapeutic options for NAFLD are still being sought. Therefore, the aim of our review was to evaluate the recently published studies on the treatment of NAFLD patients. We searched for articles in the PubMed database using appropriate terms, including “non-alcoholic fatty liver disease”, “nonalcoholic fatty liver disease”, “NAFLD”, “diet”, “treatment”, “physical activity”, “supplementation”, “surgery”, “overture” and “guidelines”. One hundred forty-eight randomized clinical trials published from January 2020 to November 2022 were used for the final analysis. The results show significant benefits of NAFLD therapy associated with the use of not only the Mediterranean but also other types of diet (including low-calorie ketogenic, high-protein, anti-inflammatory and whole-grain diets), as well as enrichment with selected food products or supplements. Significant benefits in this group of patients are also associated with moderate aerobic physical training. The available therapeutic options indicate, above all, the usefulness of drugs related to weight reduction, as well as the reduction in insulin resistance or lipids level and drugs with anti-inflammatory or antioxidant properties. The usefulness of therapy with dulaglutide and the combination of tofogliflozin with pioglitazone should be emphasized. Based on the results of the latest research, the authors of this article suggest a revision of the therapeutic recommendations for NAFLD patients. Full article

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Open AccessEditor’s ChoiceReview

Cancer Metabolism: Fasting Reset, the Keto-Paradox and Drugs for Undoing

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Maurice Israël

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Eric Berg

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Guy Tenenbaum

J. Clin. Med. 2023, 12(4), 1589; https://doi.org/10.3390/jcm12041589 - 17 Feb 2023

Viewed by 6087

Abstract

In tumor cells, ketolysis “via” succinyl-CoA: 3-oxoacid-CoAtransferase (SCOT) and acetyl-CoA acetyltransferase 1 (ACAT1) is a major source of mitochondrial acetyl-CoA. Active ACAT1 tetramers stabilize by tyrosine phosphorylation, which facilitates the SCOT reaction and ketolysis. Tyrosine phosphorylation of pyruvate kinase PK M2 has the [...] Read more.

In tumor cells, ketolysis “via” succinyl-CoA: 3-oxoacid-CoAtransferase (SCOT) and acetyl-CoA acetyltransferase 1 (ACAT1) is a major source of mitochondrial acetyl-CoA. Active ACAT1 tetramers stabilize by tyrosine phosphorylation, which facilitates the SCOT reaction and ketolysis. Tyrosine phosphorylation of pyruvate kinase PK M2 has the opposite effect, stabilizing inactive dimers, while pyruvate dehydrogenase (PDH), which is already inhibited by phosphorylation, is acetylated by ACAT1 and is doubly locked. This closes the glycolytic supply of acetyl-CoA. In addition, since tumor cells must synthesize fatty acids to create new membranes, they automatically turn off the degradation of fatty acids into acetyl-CoA (“via” the malonyl-CoA brake for the fatty acid carnityl transporter). Thus, inhibiting SCOT the specific ketolytic enzyme and ACAT1 should hold back tumor progression. However, tumor cells are still able to take up external acetate and convert it into acetyl-CoA in their cytosol “via” an acetyl-CoA synthetase, which feeds the lipogenic pathway; additionally, inhibiting this enzyme would make it difficult for tumor cells to form new lipid membrane and survive. Full article

(This article belongs to the Section Oncology)

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Open AccessEditor’s ChoiceReview

Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy

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Gian Marco Leone

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Katia Mangano

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Maria Cristina Petralia

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Ferdinando Nicoletti

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Paolo Fagone

J. Clin. Med. 2023, 12(4), 1630; https://doi.org/10.3390/jcm12041630 - 17 Feb 2023

Cited by 2 | Viewed by 1507

Abstract

Due to the key role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. Currently, five anti-TNF-α drugs have been approved: infliximab, adalimumab, golimumab, certolizumab pegol [...] Read more.

Due to the key role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. Currently, five anti-TNF-α drugs have been approved: infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. Anti-TNF-α biosimilars are also available for clinical use. Here, we will review the historical development as well as the present and potential future applications of anti-TNF-α therapies, which have led to major improvements for patients with several autoimmune diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC), psoriasis (PS) and chronic endogenous uveitis. Other therapeutic areas are under evaluation, including viral infections, e.g., COVID-19, as well as chronic neuropsychiatric disorders and certain forms of cancer. The search for biomarkers able to predict responsiveness to anti-TNF-α drugs is also discussed. Full article

(This article belongs to the Section Immunology)

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Open AccessEditor’s ChoiceArticle

Severe and Very Severe Myalgic Encephalopathy/Chronic Fatigue Syndrome ME/CFS in Norway: Symptom Burden and Access to Care

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Kristian Sommerfelt

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Trude Schei

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Arild Angelsen

J. Clin. Med. 2023, 12(4), 1487; https://doi.org/10.3390/jcm12041487 - 13 Feb 2023

Viewed by 6650

Abstract

There is a striking lack of systematic knowledge regarding the symptom burden, capacity for activities of daily living, and supportive measures for the most severely ill ME/CFS patients. The present study seeks to address this through a national, Internet-based survey targeting patients with [...] Read more.

There is a striking lack of systematic knowledge regarding the symptom burden, capacity for activities of daily living, and supportive measures for the most severely ill ME/CFS patients. The present study seeks to address this through a national, Internet-based survey targeting patients with severe and very severe ME/CFS and their carers. Responses from 491 patients were included, with 444 having severe and 47 very severe ME/CFS with the classification based on the best estimate from patient responses. In addition, 95 respondents were reclassified from patients’ own classification to moderate and included for comparison. The onset was before 15 years of age for 45% in the very severe and 32% in the severe group. Disease duration was more than 15 years for 19% in the very severe and 27% in the severe group. Patient symptom burden was extensive. The most severely affected were totally bedridden, unable to talk, and experienced dramatic worsening of symptoms after minimal activity or sensory stimuli. Care and assistance from healthcare and social services were often described as insufficient or inadequate, often worsening the symptom load and burden of care. A substantial lack of disease knowledge among healthcare providers in general was reported. Yet approximately 60% in the severe and very severe groups found services provided by occupational therapists and family doctors (general practitioners) helpful, while a smaller proportion experienced appropriate help from other health personnel groups. This indicates that help and support are highly needed and possible to provide. On the other hand, this must be approached carefully, as a substantial number of patients experienced deterioration from contact with healthcare personnel. Family carers described an extensive burden of care with often inadequate help from healthcare providers or municipal authorities. Patient care by family members of very severe ME/CFS patients constituted more than 40 h a week for 71% of this patient group. The carers described a large negative impact on their work and financial situation, and on their mental wellbeing. We conclude that childhood onset was common, burden of disease was extensive, and support from responsible societal health and social support providers was commonly grossly inadequate. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Epidemiology, Treatment and Prognosis)

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Open AccessEditor’s ChoiceArticle

Ozonized Hydrogels vs. 1% Chlorhexidine Gel for the Clinical and Domiciliary Management of Peri-Implant Mucositis: A Randomized Clinical Trial

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Andrea Butera

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Maurizio Pascadopoli

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Simone Gallo

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Carlos Pérez-Albacete Martínez

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José Eduardo Maté Sánchez de Val

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Luca Parisi

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Alice Gariboldi

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Andrea Scribante

J. Clin. Med. 2023, 12(4), 1464; https://doi.org/10.3390/jcm12041464 - 12 Feb 2023

Cited by 2 | Viewed by 1113

Abstract

Peri-implant mucositis consists of a reversible inflammation of peri-implant tissues characterized by bleeding on gentle probing in the absence of bone loss. Ozone therapy is being extensively studied for its efficacy in treating different dental conditions. To date, few studies have evaluated ozone [...] Read more.

Peri-implant mucositis consists of a reversible inflammation of peri-implant tissues characterized by bleeding on gentle probing in the absence of bone loss. Ozone therapy is being extensively studied for its efficacy in treating different dental conditions. To date, few studies have evaluated ozone as an adjunct to the oral hygiene measures of peri-implant mucositis patients. The aim of the present study is to assess the efficacy of an ozonized gel (Trial group) compared to chlorhexidine (Control group) after a domiciliary protocol of oral hygiene in a 6-month study. According to a split-mouth study design, patients were divided into Group 1 for the application of chlorhexidine gel in peri-implant mucositis sites of quadrants Q1 and Q3, whereas in quadrants Q2 and Q4, the ozonized gel was in-office administered. For Group 2, the quadrants were inverted. At baseline (T0), and after 1 (T1), 2 (T2), and 3 (T3) months, Probing Depth (PD), Plaque Index (PI), SI Suppuration Index (SI), Bleeding Score (BS) and Marginal Mucosa Condition (MMC) were measured. A statistically significant decrease was found for all the variables assessed in each group (p < 0.05), whereas significant intergroup differences were found only for PI, BoP, and BS. Accordingly, both agents tested in this study showed an efficacy in treating peri-implant mucositis. The ozonized gel deserves particular attention, considering the better outcome than chlorhexidine on specific clinical periodontal parameters, as well as its lesser shortcomings. Full article

(This article belongs to the Section Stomatology)

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Open AccessEditor’s ChoiceReview

by

Hemil Dario Rosales

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Henry Garcia Guevara

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Stefania Requejo

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Maria Dianella Jensen

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Julio Acero

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Sergio Olate

J. Clin. Med. 2023, 12(4), 1416; https://doi.org/10.3390/jcm12041416 - 10 Feb 2023

Cited by 1 | Viewed by 1003

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons (AAOMS) as the presence of an exposed bone area in the maxillofacial region, present for more than eight weeks in patients treated with the use of [...] Read more.

Medication-related osteonecrosis of the jaw (MRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons (AAOMS) as the presence of an exposed bone area in the maxillofacial region, present for more than eight weeks in patients treated with the use of antiresorptive or antiangiogenic agents, with no history of radiation or metastatic disease. Bisphosphonates (BF) and denosumab (DS) are widely used in adults for the management of patients with cancer and osteoporosis, and recently there has been an increase in their use in child and young patients for the management of disorders such as osteogenesis imperfecta (OI), glucocorticoid-induced osteoporosis, McCune-Albright syndrome (MAS), malignant hypercalcemia, and others. There are differences between case reports in adults compared to child and young patients related to the use of antiresorptive/antiangiogenic drugs and the development of MRONJ. The aim was to analyze the presence of MRONJ in children and young patients, and the relation with oral surgery. A systematic review, following the PRISMA search matrix based on the PICO question, was conducted in PubMed, Embase, ScienceDirect, Cochrane, Google Scholar, and manual search in high-impact journals between 1960 and 2022, publications in English or Spanish, including randomized and non-randomized clinical trials, prospective and retrospective cohort studies, cases and controls studies, and series and case reports. A total of 2792 articles were identified and 29 were included; all of them published between 2007 and 2022, identifying 1192 patients, 39.68% male and 36.24% female, aged 11.56 years old on average, using these drugs mainly for OI (60.15%); 4.21 years on average was the therapy time and 10.18 drug doses administered on average; oral surgery was observed in 216 subjects, reporting 14 cases of MRONJ. We concluded that there is a low presence of MRONJ in the child and youth population treated with antiresorptive drugs. Data collection is weak, and details of therapy are not clear in some cases. Deficiencies in protocols and pharmacological characterization were observed in most of the included articles. Full article

(This article belongs to the Special Issue Breakthroughs in Oral and Maxillofacial Surgery)

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Open AccessEditor’s ChoiceReview

Transcatheter Tricuspid Valve Replacement: Illustrative Case Reports and Review of State-of-Art

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Manuel Barreiro-Pérez

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Rocío González-Ferreiro

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Berenice Caneiro-Queija

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Marta Tavares-Silva

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Luis Puga

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Jose A Parada-Barcia

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Alvaro Rodriguez-Perez

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Jose A Baz-Alonso

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Miguel A Pinon-Esteban

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Rodrigo Estevez-Loureiro

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Andres Iniguez-Romo

J. Clin. Med. 2023, 12(4), 1371; https://doi.org/10.3390/jcm12041371 - 09 Feb 2023

Viewed by 5104

Abstract

Tricuspid regurgitation (TR) is one of the most common heart valve diseases, associated a with poor prognosis since significant TR is associated with an increased mortality risk compared to no TR or mild regurgitation. Surgery is the standard treatment for TR, although it [...] Read more.

Tricuspid regurgitation (TR) is one of the most common heart valve diseases, associated a with poor prognosis since significant TR is associated with an increased mortality risk compared to no TR or mild regurgitation. Surgery is the standard treatment for TR, although it is associated with high morbidity, mortality, and prolonged hospitalization, particularly in tricuspid reoperation after left-sided surgery. Thus, several innovative percutaneous transcatheter approaches for repair and replacement of the tricuspid valve have gathered significant momentum and have undergone extensive clinical development in recent years, with favorable clinical outcomes in terms of mortality and rehospitalization during the first year of follow-up. We present three clinical cases of transcatheter tricuspid valve replacement in an orthotopic position with two different innovative systems along with a review of the state-of-the-art of this emergent topic. Full article

(This article belongs to the Special Issue Transcatheter Mitral and Tricuspid Valve Repair: Advances and Challenges)

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Open AccessEditor’s ChoiceReview

Challenges in ARDS Definition, Management, and Identification of Effective Personalized Therapies

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Denise Battaglini

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Brigitta Fazzini

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Pedro Leme Silva

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Fernanda Ferreira Cruz

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J. Clin. Med. 2023, 12(4), 1381; https://doi.org/10.3390/jcm12041381 - 09 Feb 2023

Cited by 3 | Viewed by 7385

Abstract

Over the last decade, the management of acute respiratory distress syndrome (ARDS) has made considerable progress both regarding supportive and pharmacologic therapies. Lung protective mechanical ventilation is the cornerstone of ARDS management. Current recommendations on mechanical ventilation in ARDS include the use of [...] Read more.

Over the last decade, the management of acute respiratory distress syndrome (ARDS) has made considerable progress both regarding supportive and pharmacologic therapies. Lung protective mechanical ventilation is the cornerstone of ARDS management. Current recommendations on mechanical ventilation in ARDS include the use of low tidal volume (V_T) 4–6 mL/kg of predicted body weight, plateau pressure (P_PLAT) < 30 cmH₂O, and driving pressure (∆P) < 14 cmH₂O. Moreover, positive end-expiratory pressure should be individualized. Recently, variables such as mechanical power and transpulmonary pressure seem promising for limiting ventilator-induced lung injury and optimizing ventilator settings. Rescue therapies such as recruitment maneuvers, vasodilators, prone positioning, extracorporeal membrane oxygenation, and extracorporeal carbon dioxide removal have been considered for patients with severe ARDS. Regarding pharmacotherapies, despite more than 50 years of research, no effective treatment has yet been found. However, the identification of ARDS sub-phenotypes has revealed that some pharmacologic therapies that have failed to provide benefits when considering all patients with ARDS can show beneficial effects when these patients were stratified into specific sub-populations; for example, those with hyperinflammation/hypoinflammation. The aim of this narrative review is to provide an overview on current advances in the management of ARDS from mechanical ventilation to pharmacological treatments, including personalized therapy. Full article

(This article belongs to the Special Issue New Insights into Acute Respiratory Distress Syndrome)

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Open AccessEditor’s ChoiceArticle

Blood Count-Derived Inflammatory Markers and Acute Complications of Ischemic Heart Disease in Elderly Women

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J. Clin. Med. 2023, 12(4), 1369; https://doi.org/10.3390/jcm12041369 - 08 Feb 2023

Cited by 1 | Viewed by 712

Abstract

Coronary artery disease (CAD) in women occurs later than in men. Underlying atherosclerosis, a chronic process of lipoprotein deposition in arterial walls with a prominent inflammatory component, is influenced by several risk factors. In women, commonly used inflammatory markers are generally found to [...] Read more.

Coronary artery disease (CAD) in women occurs later than in men. Underlying atherosclerosis, a chronic process of lipoprotein deposition in arterial walls with a prominent inflammatory component, is influenced by several risk factors. In women, commonly used inflammatory markers are generally found to be related to the occurrence of acute coronary syndrome (ACS), as well as the development of other diseases that influence CAD. New inflammatory markers derived from total blood count—systemic inflammatory response index (SII), systemic inflammatory reaction index (SIRI), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR)—were analyzed in the group of 244 elderly, postmenopausal women with the diagnosis of ACS or stable CAD. SII, SIRI, MLR, and NLR were significantly higher in women with ACS compared to those with stable CAD (p < 0.05 for all)—the highest values were observed in women with NSTEMI. MLR from new inflammatory markers, HDL, and history of MI turned out to be significant factors associated with ACS. These results suggest that MLR as representative of blood count-derived inflammatory markers may be considered as additional CVD risk factors in women with suspected ACS. Full article

(This article belongs to the Special Issue Prevention of Cardiovascular Diseases)

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Open AccessEditor’s ChoiceReview

Sepsis-Associated Delirium: A Narrative Review

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and J-STAD (Japan Sepsis Treatment and Diagnosis) Study Group

J. Clin. Med. 2023, 12(4), 1273; https://doi.org/10.3390/jcm12041273 - 06 Feb 2023

Viewed by 3805

Abstract

Delirium is characterized by an acutely altered mental status accompanied by reductions in cognitive function and attention. Delirium in septic patients, termed sepsis-associated delirium (SAD), differs in several specific aspects from the other types of delirium that are typically encountered in intensive care [...] Read more.

Delirium is characterized by an acutely altered mental status accompanied by reductions in cognitive function and attention. Delirium in septic patients, termed sepsis-associated delirium (SAD), differs in several specific aspects from the other types of delirium that are typically encountered in intensive care units. Since sepsis and delirium are both closely associated with increased morbidity and mortality, it is important to not only prevent but also promptly diagnose and treat SAD. We herein reviewed the etiology, pathogenesis, risk factors, prevention, diagnosis, treatment, and prognosis of SAD, including coronavirus disease 2019 (COVID-19)-related delirium. Delirium by itself not only worsens long-term prognosis, but it is also regarded as an important factor affecting the outcome of post-intensive care syndrome. In COVID-19 patients, the difficulties associated with adequately implementing the ABCDEF bundle (Assess, prevent, and manage pain; Both spontaneous awakening and breathing trials: Choice of analgesia and sedation; Delirium assess, prevent, and manage; Early mobility and exercise; Family engagement/empowerment) and the need for social isolation are issues that require the development of conventional care for SAD. Full article

(This article belongs to the Special Issue Post-intensive Care Syndrome: Prevention, Current Status and Future Challenges - Part II)

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Open AccessEditor’s ChoiceReview

Do Interleukin-1 and Interleukin-6 Antagonists Hold Any Place in the Treatment of Atherosclerotic Cardiovascular Disease and Related Co-Morbidities? An Overview of Available Clinical Evidence

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Athina Dimosiari

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Dimitrios Patoulias

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George D. Kitas

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Theodoros Dimitroulas

J. Clin. Med. 2023, 12(4), 1302; https://doi.org/10.3390/jcm12041302 - 06 Feb 2023

Cited by 1 | Viewed by 734

Abstract

Cardiovascular disease (CVD) constitutes a real pandemic of the 21st century. According to data from the Centers for Disease Control and Prevention, one person dies every 34 min due to some form of CVD in the United States. Apart from the extremely high [...] Read more.

Cardiovascular disease (CVD) constitutes a real pandemic of the 21st century. According to data from the Centers for Disease Control and Prevention, one person dies every 34 min due to some form of CVD in the United States. Apart from the extremely high morbidity and mortality accompanying CVD, the economic burden seems to be unbearable even for developed countries in the Western World. The role of inflammation in the development and progression of CVD appears to be crucial, while, various inflammatory pathways, such as the Nod-like receptor protein 3 (NLRP3) inflammasome-interleukin (IL)-1/IL-6 pathway of the innate immunity, have attracted scientific interest during the last decade, as a potential treatment target in primary and/or secondary prevention of CVD. Whereas there is a significant amount of evidence, stemming mainly from observational studies, concerning the cardiovascular safety of IL-1 and IL-6 antagonists in patients with rheumatic diseases, evidence from relevant randomized controlled trials (RCTs) is rather scarce and conflicting, especially for patients without underlying rheumatic disease. In this review, we summarize and critically present the currently available evidence, both from RCTs and observational studies, concerning the place that IL-1 and IL-6 antagonists may hold in the treatment of CVD. Full article

(This article belongs to the Section Cardiovascular Medicine)

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Open AccessEditor’s ChoiceArticle

CRB-65 for Risk Stratification and Prediction of Prognosis in Pulmonary Embolism

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Christine Espinola-Klein

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Lukas Hobohm

J. Clin. Med. 2023, 12(4), 1264; https://doi.org/10.3390/jcm12041264 - 05 Feb 2023

Viewed by 7917

Abstract

Background: Pulmonary embolism (PE) is accompanied by high morbidity and mortality. The search for simple and easily assessable risk stratification scores with favourable effectiveness is still ongoing, and prognostic performance of the CRB-65 score in PE might promising. Methods: The German nationwide inpatient [...] Read more.

Background: Pulmonary embolism (PE) is accompanied by high morbidity and mortality. The search for simple and easily assessable risk stratification scores with favourable effectiveness is still ongoing, and prognostic performance of the CRB-65 score in PE might promising. Methods: The German nationwide inpatient sample was used for this study. All patient cases of patients with PE in Germany 2005–2020 were included and stratified for CRB-65 risk class: low-risk group (CRB-65-score 0 points) vs. high-risk group (CRB-65-score ≥1 points). Results: Overall, 1,373,145 patient cases of patients with PE (76.6% aged ≥65 years, 47.0% females) were included. Among these, 1,051,244 patient cases (76.6%) were classified as high-risk according to CRB-65 score (≥1 points). The majority of high-risk patients according to CRB-65 score were females (55.8%). Additionally, high-risk patients according to CRB-65 score showed an aggravated comorbidity profile with increased Charlson comorbidity index (5.0 [IQR 4.0–7.0] vs. 2.0 [0.0–3.0], p < 0.001). In-hospital case fatality (19.0% vs. 3.4%, p < 0.001) and MACCE (22.4% vs. 5.1%, p < 0.001) occurred distinctly more often in PE patients of the high-risk group according to CRB-65 score (≥1 points) compared to the low-risk group (= 0 points). The CRB-65 high-risk class was independently associated with in-hospital death (OR 5.53 [95%CI 5.40–5.65], p < 0.001) as well as MACCE (OR 4.31 [95%CI 4.23–4.40], p < 0.001). Conclusions: Risk stratification with CRB-65 score was helpful for identifying PE patients being at higher risk of adverse in-hospital events. The high-risk class according to CRB-65 score (≥1 points) was independently associated with a 5.5-fold increased occurrence of in-hospital death. Full article

(This article belongs to the Special Issue Recent Advances in Pulmonary Embolism)

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Open AccessEditor’s ChoiceReview

The Pleiotropic Role of Vitamin K in Multimorbidity of Chronic Obstructive Pulmonary Disease

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J. Clin. Med. 2023, 12(4), 1261; https://doi.org/10.3390/jcm12041261 - 05 Feb 2023

Cited by 1 | Viewed by 1561

Abstract

Although defined by the presence of airflow obstruction and respiratory symptoms, patients with chronic obstructive pulmonary disease (COPD) are characterized by multimorbidity. Numerous co-occurring conditions and systemic manifestations contribute to the clinical presentation and progression of COPD; however, underlying mechanisms for multimorbidity are [...] Read more.

Although defined by the presence of airflow obstruction and respiratory symptoms, patients with chronic obstructive pulmonary disease (COPD) are characterized by multimorbidity. Numerous co-occurring conditions and systemic manifestations contribute to the clinical presentation and progression of COPD; however, underlying mechanisms for multimorbidity are currently not fully elucidated. Vitamin A and vitamin D have been related to COPD pathogenesis. Another fat-soluble vitamin, vitamin K, has been put forward to exert protective roles in COPD. Vitamin K is an unequivocal cofactor for the carboxylation of coagulation factors, but also for extra-hepatic proteins including the soft tissue calcification inhibitor matrix Gla-protein and the bone protein osteocalcin. Additionally, vitamin K has been shown to have anti-oxidant and anti-ferroptosis properties. In this review, we discuss the potential role of vitamin K in the systemic manifestations of COPD. We will elaborate on the effect of vitamin K on prevalent co-occurring chronic conditions in COPD including cardiovascular disorders, chronic kidney disease, osteoporosis, and sarcopenia. Finally, we link these conditions to COPD with vitamin K as a connecting factor and provide recommendations for future clinical studies. Full article

(This article belongs to the Special Issue Clinical Advances in Chronic Obstructive Pulmonary Disease and Its Complications)

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Open AccessEditor’s ChoiceArticle

Immediate Effects of Myofascial Release Treatment on Lumbar Microcirculation: A Randomized, Placebo-Controlled Trial

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J. Clin. Med. 2023, 12(4), 1248; https://doi.org/10.3390/jcm12041248 - 04 Feb 2023

Cited by 1 | Viewed by 3211

Abstract

(1) Background: Inflammatory processes in the thoracolumbar fascia (TLF) lead to thickening, compaction, and fibrosis and are thought to contribute to the development of nonspecific low back pain (nLBP). The blood flow (BF) of fascial tissue may play a critical role in this [...] Read more.

(1) Background: Inflammatory processes in the thoracolumbar fascia (TLF) lead to thickening, compaction, and fibrosis and are thought to contribute to the development of nonspecific low back pain (nLBP). The blood flow (BF) of fascial tissue may play a critical role in this process, as it may promote hypoxia-induced inflammation. The primary objective of the study was to examine the immediate effects of a set of myofascial release (MFR) techniques on the BF of lumbar myofascial tissue. The secondary objectives were to evaluate the influence of TLF morphology (TLFM), physical activity (PA), and body mass index (BMI) on these parameters and their correlations with each other. (2) Methods: This study was a single-blind, randomized, placebo-controlled trial. Thirty pain-free subjects (40.5 ± 14.1 years) were randomly assigned to two groups treated with MFR or a placebo intervention. Correlations between PA, BMI, and TLFM were calculated at baseline. The effects of MFR and TLFM on BF (measured with white light and laser Doppler spectroscopy) were determined. (3) Results: The MFR group had a significant increase in BF after treatment (31.6%) and at follow-up (48.7%) compared with the placebo group. BF was significantly different between disorganized and organized TLFM (p < 0.0001). There were strong correlations between PA (r = −0.648), PA (d = 0.681), BMI (r = −0.798), and TLFM. (4) Conclusions: Impaired blood flow could lead to hypoxia-induced inflammation, possibly resulting in pain and impaired proprioceptive function, thereby likely contributing to the development of nLBP. Fascial restrictions of blood vessels and free nerve endings, which are likely associated with TLFM, could be positively affected by the intervention in this study. Full article

(This article belongs to the Special Issue Physiological, Pathophysiological and Biomechanical Factors Associated With Fascial Tissue Properties in Clinical Context)

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Open AccessEditor’s ChoiceReview

Stent Thrombosis and Restenosis with Contemporary Drug-Eluting Stents: Predictors and Current Evidence

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J. Clin. Med. 2023, 12(3), 1238; https://doi.org/10.3390/jcm12031238 - 03 Feb 2023

Cited by 2 | Viewed by 1424

Abstract

Iterations in stent technologies, advances in pharmacotherapy, and awareness of the implications of implantation techniques have markedly reduced the risk of stent failure, both in the form of stent thrombosis (ST) and in-stent restenosis (ISR). However, given the number of percutaneous coronary interventions [...] Read more.

Iterations in stent technologies, advances in pharmacotherapy, and awareness of the implications of implantation techniques have markedly reduced the risk of stent failure, both in the form of stent thrombosis (ST) and in-stent restenosis (ISR). However, given the number of percutaneous coronary interventions (PCI) performed worldwide every year, ST and ISR, albeit occurring at a fairly low rate, represent a public health problem even with contemporary DES platforms. The understanding of mechanisms and risk factors for these two PCI complications has been of fundamental importance for the parallel evolution of stent technologies. Risk factors associated with ST and ISR are usually divided into patient-, lesion-, device- and procedure-related. A number of studies have shown how certain risk factors are related to early (1 month) versus late/very late ST (between 1 month and 1 year and >1 year, respectively). However, more research is required to conclusively show the role of time-dependence of risk factors also in the incidence of ISR (early [1 year] or late [>1 year]). A thorough risk assessment is required due to the complex etiology of ST and ISR. The most effective strategy to treat ST and ISR is still to prevent them; hence, it is crucial to identify patient-, lesion-, device- and procedure-related predictors. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Coronary Artery Disease)

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Open AccessEditor’s ChoiceReview

Diagnostics of Sacroiliac Joint Differentials to Axial Spondyloarthritis Changes by Magnetic Resonance Imaging

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Anne Grethe Jurik

J. Clin. Med. 2023, 12(3), 1039; https://doi.org/10.3390/jcm12031039 - 29 Jan 2023

Cited by 1 | Viewed by 3268

Abstract

The diagnosis of axial spondyloarthritis (axSpA) is usually based on a pattern of imaging and clinical findings due to the lack of diagnostic criteria. The increasing use of magnetic resonance imaging (MRI) of the sacroiliac joints (SIJ) to establish the diagnosis early in [...] Read more.

The diagnosis of axial spondyloarthritis (axSpA) is usually based on a pattern of imaging and clinical findings due to the lack of diagnostic criteria. The increasing use of magnetic resonance imaging (MRI) of the sacroiliac joints (SIJ) to establish the diagnosis early in the pre-radiographic phase has resulted in a shift in the paradigm with an increasing frequency of axSpA diagnoses and a changed sex distribution. Non-radiographic axSpA affects males and females nearly equally, whereas ankylosing spondylitis predominantly occurs in males. The MRI-based increasing frequency of axSpA in women is mainly due to the presence of subchondral bone marrow edema (BME) on fluid-sensitive MR sequences, which may be a non-specific finding in both women and men. Due to the somewhat different pelvic tilt and SIJ anatomy, women are more prone than men to develop strain-related MRI changes and may have pregnancy-related changes. Awareness of non-specific subchondral BME at the SIJ is important as it can imply a risk for an incorrect SpA diagnosis, especially as the clinical manifestations of axSpA may also be non-specific. Knowledge of relevant MRI and clinical features of differential diagnoses is needed in the diagnostic workout of patients with suspected axSpA considering that non-SpA-related SIJ conditions are more common in patients with low back or buttock pain than axSpA sacroiliitis. The purpose of this review was to present current knowledge of the most frequent differential diagnoses to axSpA sacroiliitis by MRI taking the clinical characteristics into account. Full article

(This article belongs to the Special Issue Imaging of Arthropathies and Tendinopathies)

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Open AccessEditor’s ChoiceArticle

Simultaneous Bilateral Total Hip Arthroplasty with Straight-Stems and Short-Stems: Does the Short One Do a Better Job?

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J. Clin. Med. 2023, 12(3), 1028; https://doi.org/10.3390/jcm12031028 - 29 Jan 2023

Cited by 2 | Viewed by 753

Abstract

Background: Total hip arthroplasty (THA) is known to be the most successful orthopaedic surgery of the last century, but it is still struggling with controversies concerning one-stage bilateral THA. The current study aimed to compare the clinical outcome of patients with unilateral or [...] Read more.

Background: Total hip arthroplasty (THA) is known to be the most successful orthopaedic surgery of the last century, but it is still struggling with controversies concerning one-stage bilateral THA. The current study aimed to compare the clinical outcome of patients with unilateral or simultaneous bilateral THA by using short-stem and straight-stem designs and focusing on operation time, blood loss, and length of hospital stay (LOS). Material and Methods: Between 2006 and 2018, 92 patients were enrolled in this study. Forty-six patients underwent a bilateral THA in one session, and forty-six matched patients underwent a unilateral THA. In each of the two groups (unilateral vs. bilateral), 23 patients received either a straight (unilateral: 10 females, 13 males, mean age 63; bilateral: 12 females, 11 males, mean age 53 years) or short stem (unilateral: 11 females, 12 males, mean age 60 years; bilateral: 12 females, 11 males, 53 mean age 62 years). The blood count was checked preoperatively as well as one and three days after surgery. Furthermore, the operation time and LOS were investigated. Results: Compared to THA with straight-stems, short-stem THA showed significantly less blood loss; there was no difference in the LOS of both groups. A significantly shorter operative time was only observed in the bilateral THA. Conclusion: The current study showed that simultaneous bilateral THA appears to be safe and reliable in patients without multiple comorbidities. In addition, short-stem THA appears to be beneficial in terms of clinical performance and outcome, and it appears to be superior to straight-stem THA, regardless of whether the patient underwent unilateral or simultaneous bilateral THA. Full article

(This article belongs to the Special Issue Joint Repair and Replacement: Clinical Updates and Perspectives)

Open AccessEditor’s ChoiceArticle

Parents Rate Problematic Video Streaming in Adolescents: Conceptualization and External Assessment of a New Clinical Phenomenon Based on the ICD-11 Criteria of Gaming Disorder

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Kerstin Paschke

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Ann-Kathrin Napp

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Rainer Thomasius

J. Clin. Med. 2023, 12(3), 1010; https://doi.org/10.3390/jcm12031010 - 28 Jan 2023

Cited by 1 | Viewed by 864

Abstract

In recent years, video streaming (VS) increased substantially. Adolescents are at significant risk of presenting problematic VS patterns associated with a spectrum of mental-health difficulties. Because VS platforms rely on similar mechanisms as digital games, the ICD-11 criteria for Gaming Disorder (GD) have [...] Read more.

In recent years, video streaming (VS) increased substantially. Adolescents are at significant risk of presenting problematic VS patterns associated with a spectrum of mental-health difficulties. Because VS platforms rely on similar mechanisms as digital games, the ICD-11 criteria for Gaming Disorder (GD) have been successfully implemented to measure Streaming Disorder (StrD) in adolescents. For proper diagnoses, external rating scales are urgently required in addition to self-reports. The Streaming Disorder Scale for Parents (STREDIS-P) was created and validated in a representative sample of n = 891 adolescent-parent dyads. Mental health problems were assessed with standardized instruments. Confirmatory factor analysis was conducted to examine the underlying factor structure. Cutoff scores were determined using ROC analysis. Accordance between parental and adolescents’ self-ratings was calculated. Consistent with the results of previous validation studies for screening instruments assessing similar phenomena based on ICD-11-GD criteria, two factors, cognitive-behavioral symptoms and negative consequences, were confirmed. STREDIS-P demonstrated good to excellent internal consistency, criterion validity, and discriminatory power. Accordance with adolescents’ self-ratings was moderate. STREDIS-P is the first screening tool for assessing StrD in adolescents by parental ratings. It is highly relevant for conceptualizing a new phenomenon in clinical routine and academic research. Full article

(This article belongs to the Collection Gambling, Gaming and Other Behavioural Addictions)

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Open AccessEditor’s ChoiceArticle

Biomarkers and Predictive Factors for Treatment Response to Tumor Necrosis Factor-α Inhibitors in Patients with Psoriasis

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Teppei Hagino

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Hidehisa Saeki

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Naoko Kanda

J. Clin. Med. 2023, 12(3), 974; https://doi.org/10.3390/jcm12030974 - 27 Jan 2023

Cited by 1 | Viewed by 829

Abstract

We performed a retrospective and observational study of patients with psoriasis. The aim of this study was to define the laboratory indicators reflecting the treatment response to tumor necrosis factor (TNF)-α inhibitors and the predictors for the treatment response. From January 2010 to [...] Read more.

We performed a retrospective and observational study of patients with psoriasis. The aim of this study was to define the laboratory indicators reflecting the treatment response to tumor necrosis factor (TNF)-α inhibitors and the predictors for the treatment response. From January 2010 to June 2022, 28, 15 and 12 patients with psoriasis were treated with infliximab (IFX), adalimumab (ADA) and certolizumab pegol (CZP), respectively. The values of C-reactive protein (CRP), platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio and monocyte to lymphocyte ratio decreased in parallel with psoriasis area and severity index (PASI) at weeks 12 and 52 of treatment. The percentage reduction of the CRP was correlated with that of the PASI at week 52 in all patients and subgroups treated with IFX. The percentage reduction of the PLR was correlated with that of the PASI at week 52 in all patients. Linear multivariate regression analyses revealed that the presence of scalp lesions was associated with a high percentage reduction of the PASI at week 52 in the ADA subgroup. The CRP and PLR might act as biomarkers reflecting the treatment response to TNF-α inhibitors in patients with psoriasis. The presence of scalp lesions might be a predictive factor for a high treatment response to ADA in patients with psoriasis. Full article

(This article belongs to the Special Issue Psoriasis and Psoriatic Arthritis: How to Treat in the Era of Biologics and Small Molecule Inhibitors?—Part 2)

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Open AccessEditor’s ChoiceArticle

Salivary Human β-Defensin 1-3 and Human α-Defensin-1 Levels in Relation to the Extent of Periodontal Disease and Tooth Loss in the Elderly

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J. Clin. Med. 2023, 12(3), 976; https://doi.org/10.3390/jcm12030976 - 27 Jan 2023

Cited by 1 | Viewed by 608

Abstract

The oral innate immune response may diminish with aging. In the present study, the aim was to examine human β-defensin (hBD) 1-3 and human neutrophil peptide (HNP)-1 levels in the saliva of an elderly population to establish the extent of periodontal disease and [...] Read more.

The oral innate immune response may diminish with aging. In the present study, the aim was to examine human β-defensin (hBD) 1-3 and human neutrophil peptide (HNP)-1 levels in the saliva of an elderly population to establish the extent of periodontal disease and tooth loss. A total of 175 individuals aged ≥ 65 years were divided into five groups based on the number of teeth with a pocket depth ≥ 4 mm as follows: 17 pocket-free individuals (Control), 55 individuals having 1–6 pocket teeth (PerioA), 33 individuals having 7–13 pocket teeth (PerioB), 29 individuals having at least 14 pocket teeth (PerioC), and 41 edentulous individuals. Their salivary defensin levels were measured with ELISA kits. The salivary HNP-1 levels were significantly higher in the Perio groups (PerioB: p < 0.001 and PerioC: p < 0.001) in comparison to the Control. The associations between salivary HNP-1 levels and the number of pocket teeth remained significant after adjustments for age, gender, level of education, and number of teeth. The salivary HNP and hBD levels differed in terms of their correlation to the extent of periodontal disease and tooth loss in the elderly. Full article

(This article belongs to the Section Stomatology)

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Open AccessEditor’s ChoiceArticle

Prevalence of Overweight and Obesity in France: The 2020 Obepi-Roche Study by the “Ligue Contre l’Obésité”

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Annick Fontbonne

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Andrew Currie

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Patrick Tounian

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Marie-Christine Picot

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Olivier Foulatier

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Marius Nedelcu

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David Nocca

J. Clin. Med. 2023, 12(3), 925; https://doi.org/10.3390/jcm12030925 - 25 Jan 2023

Cited by 2 | Viewed by 6320

Abstract

Obepi-Roche 2020 by the “Ligue Contre l’Obésité” (League Against Obesity) estimated overweight and obesity prevalence in France. The adopted methodology was chosen to be as similar as possible to that of a series of quota-based surveys conducted every three years from 1997 to [...] Read more.

Obepi-Roche 2020 by the “Ligue Contre l’Obésité” (League Against Obesity) estimated overweight and obesity prevalence in France. The adopted methodology was chosen to be as similar as possible to that of a series of quota-based surveys conducted every three years from 1997 to 2012 (Obepi-Roche studies). The 2020 survey was conducted online from 24th September to 5th October 2020 by the Odoxa polling institute on a sample of metropolitan French subjects aged 18 years or over. Participants (n = 9598) self-measured their height and weight according to detailed instructions. Prevalence estimates were produced for all categories of body mass index. The prevalence of excess weight was 47.3% (17.0% of subjects with obesity), with higher values in the north and east of France. When comparing these 2020 estimates to previous Obepi-Roche estimates in order to visualize trends since 1997, it appeared that overweight fluctuated around 30%, and obesity prevalence increased steadily at a rapid pace. The increase was even steeper in the youngest age groups and for severe and complex obesity. Given the slightly different methodologies between the 1997–2012 studies and the 2020 survey, the worrying trends in obesity prevalence since 1997 must be confirmed, calling for a reedition of the Obepi-Roche series. Full article

(This article belongs to the Special Issue New Treatments in Bariatric Surgery)

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Open AccessEditor’s ChoiceArticle

Soft-Tissue Augmentation around Dental Implants with a Connective Tissue Graft (CTG) and Xenogeneic Collagen Matrix (CMX)—5-Year Follow-Up

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J. Clin. Med. 2023, 12(3), 924; https://doi.org/10.3390/jcm12030924 - 24 Jan 2023

Cited by 1 | Viewed by 1698

Abstract

Proper horizontal and vertical thickness of the gingival connective tissue has been proven to be one of the success criteria in dental implant and reconstructive surgery. When thin tissue is found, gingiva augmentation methods can be used to increase the quality and volume [...] Read more.

Proper horizontal and vertical thickness of the gingival connective tissue has been proven to be one of the success criteria in dental implant and reconstructive surgery. When thin tissue is found, gingiva augmentation methods can be used to increase the quality and volume of the tissue. Many methods have been described, among them pedicle soft-tissue flaps or autogenic tissue grafts. As an alternative to patients’ own tissue, xenogenic materials can be used for grafting. The fundamental issue is to choose a material that will ensure the maximum therapeutic effect, while also minimizing the negative influence on the patient’s health. The aim of this study was to compare gingival augmentation procedures using a palatal connective tissue graft (CTG) and an xenogenic soft-tissue substitute, Geistlich Mucograft (xenogeneic collagen matrix; CMX), and assess whether the timing of the graft surgery influences the clinical outcomes. The original study was a randomized control trial with a total of 75 implants placed. The patients received the soft-tissue thickening 3 months before the implant placement or 3 months after the implant placement (depending on the group). A connective tissue graft (CTG) or Geistlich Mucograft were used (depending on the group). For both the CTG and Geistlich Mucograft, better clinical outcomes were observed for maintaining the alveolar bone level and the thickness of the attached gingiva compared to the control group with no gingival augmentation. The Geistlich Mucograft showed good clinical performance in comparison to the control. Soft-tissue augmentation with the CTG before the implant placement was found to be most efficient method in terms of a stable increase of the tissue thickness since, throughout the entire observation period, the greatest increase of 1.035 mm (SD = 0.73 mm) in thickness was observed. Statistically important differences in the tissue thickness baseline compared after 5 years were observed for groups G1 vs. G2b (no augmentation vs. CTG before), G1 vs. G3b (no augmentation vs. CTG after) and for groups G2b vs. G3a (CTG before vs. CMX after). Full article

(This article belongs to the Special Issue Clinical Advances in Osseointegrated Oral Implants)

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Open AccessEditor’s ChoiceReview

Integrative and Mechanistic Approach to the Hair Growth Cycle and Hair Loss

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Nicole Natarelli

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Nimrit Gahoonia

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Raja K. Sivamani

J. Clin. Med. 2023, 12(3), 893; https://doi.org/10.3390/jcm12030893 - 23 Jan 2023

Cited by 1 | Viewed by 3142

Abstract

The hair cycle is composed of four primary phases: anagen, catagen, telogen, and exogen. Anagen is a highly mitotic phase characterized by the production of a hair shaft from the hair follicle, whereas catagen and telogen describe regression and the resting phase of [...] Read more.

The hair cycle is composed of four primary phases: anagen, catagen, telogen, and exogen. Anagen is a highly mitotic phase characterized by the production of a hair shaft from the hair follicle, whereas catagen and telogen describe regression and the resting phase of the follicle, respectively, ultimately resulting in hair shedding. While 9% of hair follicles reside in telogen at any time, a variety of factors promote anagen to telogen transition, including inflammation, hormones, stress, nutritional deficiency, poor sleep quality, and cellular division inhibiting medication. Conversely, increased blood flow, direct stimulation of the hair follicle, and growth factors promote telogen to anagen transition and subsequent hair growth. This review seeks to comprehensively describe the hair cycle, anagen and telogen balance, factors that promote anagen to telogen transition and vice versa, and the clinical utility of a variety of lab testing and evaluations. Ultimately, a variety of factors impact the hair cycle, necessitating a holistic approach to hair loss. Full article

(This article belongs to the Section Dermatology)

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Open AccessEditor’s ChoiceArticle

Stressor-Specific Sex Differences in Amygdala–Frontal Cortex Networks

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Christian Windischberger

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Ewald Moser

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Birgit Derntl

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Lydia Kogler

J. Clin. Med. 2023, 12(3), 865; https://doi.org/10.3390/jcm12030865 - 22 Jan 2023

Cited by 1 | Viewed by 721

Abstract

Females and males differ in stress reactivity, coping, and the prevalence rates of stress-related disorders. According to a neurocognitive framework of stress coping, the functional connectivity between the amygdala and frontal regions (including the dorsolateral prefrontal cortex (dlPFC), ventral anterior cingulate cortex (vACC), [...] Read more.

Females and males differ in stress reactivity, coping, and the prevalence rates of stress-related disorders. According to a neurocognitive framework of stress coping, the functional connectivity between the amygdala and frontal regions (including the dorsolateral prefrontal cortex (dlPFC), ventral anterior cingulate cortex (vACC), and medial prefrontal cortex (mPFC)) plays a key role in how people deal with stress. In the current study, we investigated the effects of sex and stressor type in a within-subject counterbalanced design on the resting-state functional connectivity (rsFC) of the amygdala and these frontal regions in 77 healthy participants (40 females). Both stressor types led to changes in subjective ratings, with decreasing positive affect and increasing negative affect and anger. Females showed higher amygdala–vACC and amygdala–mPFC rsFC for social exclusion than for achievement stress, and compared to males. Whereas a higher amygdala–vACC rsFC indicates the activation of emotion processing and coping, a higher amygdala–mPFC rsFC indicates feelings of reward and social gain, highlighting the positive effects of social affiliation. Thus, for females, feeling socially affiliated might be more fundamental than for males. Our data indicate interactions of sex and stressor in amygdala–frontal coupling, which translationally contributes to a better understanding of the sex differences in prevalence rates and stress coping. Full article

(This article belongs to the Section Mental Health)

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Open AccessEditor’s ChoiceReview

Acute Heart Failure: Diagnostic–Therapeutic Pathways and Preventive Strategies—A Real-World Clinician’s Guide

J. Clin. Med. 2023, 12(3), 846; https://doi.org/10.3390/jcm12030846 - 20 Jan 2023

Cited by 1 | Viewed by 3324

Abstract

Acute heart failure (AHF) is the most frequent cause of unplanned hospital admission in patients of >65 years of age and it is associated with significantly increased morbidity, mortality, and healthcare costs. Different AHF classification criteria have been proposed, mainly reflecting the clinical [...] Read more.

Acute heart failure (AHF) is the most frequent cause of unplanned hospital admission in patients of >65 years of age and it is associated with significantly increased morbidity, mortality, and healthcare costs. Different AHF classification criteria have been proposed, mainly reflecting the clinical heterogeneity of the syndrome. Regardless of the underlying mechanism, peripheral and/or pulmonary congestion is present in the vast majority of cases. Furthermore, a marked reduction in cardiac output with peripheral hypoperfusion may occur in most severe cases. Diagnosis is made on the basis of signs and symptoms, laboratory, and non-invasive tests. After exclusion of reversible causes, AHF therapeutic interventions mainly consist of intravenous (IV) diuretics and/or vasodilators, tailored according to the initial hemodynamic status with the addition of inotropes/vasopressors and mechanical circulatory support if needed. The aim of this review is to discuss current concepts on the diagnosis and management of AHF in order to guide daily clinical practice and to underline the unmet needs. Preventive strategies are also discussed. Full article

(This article belongs to the Special Issue New Advances in Pharmacologic and Non-pharmacologic Therapy in Heart Failure and Heart Transplant)

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Open AccessEditor’s ChoiceReview

Optimization of Transspinal Stimulation Applications for Motor Recovery after Spinal Cord Injury: Scoping Review

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Muhammad Uzair Rehman

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J. Clin. Med. 2023, 12(3), 854; https://doi.org/10.3390/jcm12030854 - 20 Jan 2023

Cited by 2 | Viewed by 1204

Abstract

Spinal cord injury (SCI) is a debilitating condition that can significantly affect an individual’s life, causing paralysis, autonomic dysreflexia, and chronic pain. Transspinal stimulation (TSS) is a non-invasive form of neuromodulation that activates the underlying neural circuitries of the spinal cord. Application of [...] Read more.

Spinal cord injury (SCI) is a debilitating condition that can significantly affect an individual’s life, causing paralysis, autonomic dysreflexia, and chronic pain. Transspinal stimulation (TSS) is a non-invasive form of neuromodulation that activates the underlying neural circuitries of the spinal cord. Application of TSS can be performed through multiple stimulation protocols, which may vary in the electrodes’ size or position as well as stimulation parameters, and which may influence the response of motor functions to the stimulation. Due to the novelty of TSS, it is beneficial to summarize the available evidence to identify the range of parameters that may provide the best outcomes for motor response. The PubMed and Google Scholar databases were searched for studies examining the effects of TSS on limb motor function. A literature search yielded 34 studies for analysis, in which electrode placement and stimulation parameters varied considerably. The stimulation protocols from each study and their impact on limb motor function were summarized. Electrode placement was variable based on the targeted limb. Studies for the upper limbs targeted the cervical enlargement with anatomical placement of the cathode over the cervical vertebral region. In lower-limb studies, the cathode(s) were placed over the thoracic and lumbar vertebral regions, to target the lumbar enlargement. The effects of carrier frequency were inconclusive across the studies. Multisite cathodal placements yielded favorable motor response results compared to single-site placement. This review briefly summarized the current mechanistic evidence of the effect of TSS on motor response after SCI. Our findings indicate that optimization of stimulation parameters will require future randomized controlled studies to independently assess the effects of different stimulation parameters under controlled circumstances. Full article

(This article belongs to the Special Issue Clinical Application of Neuromuscular Electrical Stimulation)

Open AccessEditor’s ChoiceArticle

How Adalimumab Impacts Antibiotic Prescriptions in Patients Affected by Hidradenitis Suppurativa: A 1-Year Prospective Study and Retrospective Analysis

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J. Clin. Med. 2023, 12(3), 837; https://doi.org/10.3390/jcm12030837 - 20 Jan 2023

Cited by 1 | Viewed by 587

Abstract

We conducted a one-year prospective study involving the enrollment of 58 patients with Hidradenitis Suppurativa. Through a retrospective analysis of data on the same patients, with reference to the year prior to the initiation of the anti-TNFα drug adalimumab, we aimed to show [...] Read more.

We conducted a one-year prospective study involving the enrollment of 58 patients with Hidradenitis Suppurativa. Through a retrospective analysis of data on the same patients, with reference to the year prior to the initiation of the anti-TNFα drug adalimumab, we aimed to show how the advent of this biologic therapy changes the number of days of antibiotic therapy, the number of flare-ups per year, and their duration in days, as well as the quality of life and perceived pain of patients. Full article

(This article belongs to the Section Dermatology)

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Open AccessEditor’s ChoiceArticle

Can Color Doppler Ultrasound Be Effectively Used as the Follow-Up Modality in Patients Undergoing Splenic Artery Aneurysm Embolization? A Correlational Study between Doppler Ultrasound, Magnetic Resonance Angiography and Digital Subtraction Angiography

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Krzysztof Lamparski

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Grzegorz Procyk

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Krzysztof Bartnik

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Krzysztof Korzeniowski

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Magdalena Januszewicz

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J. Clin. Med. 2023, 12(3), 792; https://doi.org/10.3390/jcm12030792 - 19 Jan 2023

Cited by 1 | Viewed by 674

Abstract

Splenic artery aneurysm (SAAs) rupture is associated with a high mortality rate. Regular surveillance with imaging before and after intervention is crucial to guide best evidence treatment. The following study aimed to determine the efficacy of color Doppler ultrasound imaging (DUS) compared to [...] Read more.

Splenic artery aneurysm (SAAs) rupture is associated with a high mortality rate. Regular surveillance with imaging before and after intervention is crucial to guide best evidence treatment. The following study aimed to determine the efficacy of color Doppler ultrasound imaging (DUS) compared to digital subtraction angiography (DSA) and magnetic resonance angiography (MRA) as a follow-up modality after selective coil embolization of true SAAs. We analyzed data from 20 patients, 15 females (48.1 ± 16.1 years) undergoing selective SAA coil embolization using detachable fibered embolization coils. Imaging using DUS, MRA, and DSA was performed 3 months after the initial embolization or the consequent re-embolization procedure. Primary clinical success, defined as Class I aneurysm occlusion, on 3-month follow-up was seen in 16 (80.0%) patients. DUS had a sensitivity of 94.4% and a specificity of 42.9% when compared to DSA and 92.3% and 30%, respectively, when compared to MRA in identifying Class I aneurysm occlusion. The positive predictive value (PPV) of DUS in identifying the need for re-embolization was 75.0%, while the NPV of DUS in these terms was 90.5%. DUS showed a high sensitivity in detecting aneurysm occlusion and clinical success, simultaneously exhibiting poor specificity. Still, with caution, this follow-up modality could be used for monitoring select low-risk patients after selective embolization of SAAs. DUS could provide a higher cost-to-benefit ratio, enabling more systematic post-procedural follow-up, as it is far more commonly used compared to MRA and non-invasive compared to DSA. Full article

(This article belongs to the Special Issue "Visceral Aneurysm" in 2022: Recent Advances and Treatment)

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Open AccessEditor’s ChoiceReview

The Advanced Diabetes Technologies for Reduction of the Frequency of Hypoglycemia and Minimizing the Occurrence of Severe Hypoglycemia in Children and Adolescents with Type 1 Diabetes

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Tatsuhiko Urakami

J. Clin. Med. 2023, 12(3), 781; https://doi.org/10.3390/jcm12030781 - 18 Jan 2023

Cited by 1 | Viewed by 771

Abstract

Hypoglycemia is an often-observed acute complication in the management of children and adolescents with type 1 diabetes. It causes inappropriate glycemic outcomes and may impair the quality of life in the patients. Severe hypoglycemia with cognitive impairment, such as a convulsion and coma, [...] Read more.

Hypoglycemia is an often-observed acute complication in the management of children and adolescents with type 1 diabetes. It causes inappropriate glycemic outcomes and may impair the quality of life in the patients. Severe hypoglycemia with cognitive impairment, such as a convulsion and coma, is a lethal condition and is associated with later-onset cognitive impairment and brain-structural abnormalities, especially in young children. Therefore, reducing the frequency of hypoglycemia and minimizing the occurrence of severe hypoglycemia are critical issues in the management of children and adolescents with type 1 diabetes. Advanced diabetes technologies, including continuous glucose monitoring and sensor-augmented insulin pumps with low-glucose suspension systems, can reduce the frequency of hypoglycemia and the occurrence of severe hypoglycemia without aggravating glycemic control. The hybrid closed-loop system, an automated insulin delivery system, must be the most promising means to achieve appropriate glycemic control with preventing severe hypoglycemia. The use of these advanced diabetes technologies could improve glycemic outcomes and the quality of life in children and adolescents with type 1 diabetes. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics, and Therapeutics in Neonatal and Pediatric Diseases: Prospective and Retrospective Clinical Studies)

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Open AccessEditor’s ChoiceArticle

Two-Years Follow-Up of Symptoms and Return to Work in Complex Post-COVID-19 Patients

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Erika Van Wambeke

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Cécile Bezler

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Anne-Marie Kasprowicz

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Anne-Laure Charles

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Emmanuel Andres

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Bernard Geny

J. Clin. Med. 2023, 12(3), 741; https://doi.org/10.3390/jcm12030741 - 17 Jan 2023

Cited by 3 | Viewed by 19626

Abstract

Introduction: Many COVID-19 patients present with severe long-lasting symptoms. They might benefit from a coordination team to manage such complex situations, but late efficacy still needs to be determined. Population and Methods: Out of 105 contacts, 45 patients had two phone consultations separated [...] Read more.

Introduction: Many COVID-19 patients present with severe long-lasting symptoms. They might benefit from a coordination team to manage such complex situations, but late efficacy still needs to be determined. Population and Methods: Out of 105 contacts, 45 patients had two phone consultations separated by personalized support 15 and 22 months, respectively, after COVID infection. Self-reported symptoms, feelings of improvement and ability to return to work allowed us to determine the efficacy of the therapeutic strategy proposed. Results: Unlike what was expected, many post-COVID-19 patients directly contacted the coordination team and had significant pre-existing comorbidities. Despite exercise, respiratory, olfactory rehabilitations, cognition/speech therapy and/or psychological support, the more frequent self-reported symptoms (fatigue, neurocognitive disorders, muscles and joint pain) did not resolve. However, dyspnea, anxiety and chest pain were significantly reduced. Finally, 2/3 of the patients felt some degree of improvement and returned to work either partially or fully, but 1/3 remained complaining of symptoms and out of work as late as 22 months after COVID occurrence. All patients greatly appreciated the second phone consultation. Conclusions: In such complex situations, besides early and adapted rehabilitations and psychological help allowing better symptom management, relatively simple actions such as a phone call might be very useful to reduce patients’ feelings of abandonment. Full article

(This article belongs to the Special Issue Long COVID: Current Approaches and Clinical Challenges in Treatment and Rehabilitation)

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Chemotherapy in Well Differentiated Neuroendocrine Tumors (NET) G1, G2, and G3: A Narrative Review

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J. Clin. Med. 2023, 12(2), 717; https://doi.org/10.3390/jcm12020717 - 16 Jan 2023

Cited by 1 | Viewed by 1272

Abstract

Neuroendocrine tumors (NETs) are rare neoplasms with a wide spectrum of clinical behavior, from the long survival of well-differentiated NETs to the dismal prognosis of high-grade neuroendocrine carcinomas (NECs), being G3 NETs a recently recognized intermediate entity. While the role of chemotherapy is [...] Read more.

Neuroendocrine tumors (NETs) are rare neoplasms with a wide spectrum of clinical behavior, from the long survival of well-differentiated NETs to the dismal prognosis of high-grade neuroendocrine carcinomas (NECs), being G3 NETs a recently recognized intermediate entity. While the role of chemotherapy is well established in NECs, data on NETs mostly derives from small studies, experts’ opinions, and extrapolating results from small-cell lung cancer studies. This narrative review aims to summarize available evidence about the use of chemotherapy in the setting of G1-2 NETs and G3 NETs. We performed literature research in PubMed Library for all articles published up to September 2022 about the efficacy of chemotherapy in NETs. Treatment regimens with STZ-5FU, CAPTEM, and anti-metabolite-based treatment are the most active and tolerated in gastroenteropancreatic NETs (GEP-NETs) G1-G2, while platinum-based regimens (FOLFOX/XELOX) and TEM/CAPTEM showed the best activity in thoracic NETs. Solid evidence about chemotherapy efficacy in G3 NETs is still lacking. Literature data support the use of chemotherapy in low-intermediate grade NETs after the failure of other therapies or if tumor shrinkage is needed. Studies assessing G3 NETs independently from NECs are needed to better understand the role of chemotherapy in this setting. Full article

(This article belongs to the Special Issue Neuroendocrine Tumors: Challenges and Future Perspectives)

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Open AccessEditor’s ChoiceArticle

Adiponectin, Leptin and Resistin in Patients with Psoriasis

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Sylwia Słuczanowska-Głabowska

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J. Clin. Med. 2023, 12(2), 663; https://doi.org/10.3390/jcm12020663 - 13 Jan 2023

Cited by 1 | Viewed by 861

Abstract

Psoriasis is a common chronic, inflammatory skin disease characterised by keratinocyte hyperproliferation, parakeratosis, and T-cell infiltration. Adipose tissue has an endocrine function, producing an abundance of cytokines and adipokines. It has also been described that the major adipokines, leptin, resistin, and adiponectin, may [...] Read more.

Psoriasis is a common chronic, inflammatory skin disease characterised by keratinocyte hyperproliferation, parakeratosis, and T-cell infiltration. Adipose tissue has an endocrine function, producing an abundance of cytokines and adipokines. It has also been described that the major adipokines, leptin, resistin, and adiponectin, may be involved in the pathogenesis of psoriasis. The aim of the study was to examine the plasma levels of adiponectin, leptin, and resistin in patients with psoriasis and their correlations with disease activity parameters: Psoriasis Activity Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Body Surface Area (BSA) index, as well as selected clinical parameters. The study included 53 patients with the plaque type and 31 healthy controls. The plasma concentrations of adiponectin were significantly lower in patients with psoriasis (p < 0.001) than in the control group. The plasma concentrations of leptin were higher in patients with psoriasis, however, due to high intra-patient variability of leptin plasma concentrations these differences did not reach statistical significance (p = 0.2). The plasma concentrations of resistin were significantly increased in patients with psoriasis compared to healthy controls (p = 0.02). There were no statistically significant correlations between adiponectin and leptin plasma concentrations and values of PASI, DLQI, and BSA. The resistin plasma concentrations correlated significantly with DLQI values. Additionally, we examined the correlations between adiponectin, leptin, and resistin plasma concentrations, and selected clinical parameters. Plasma concentrations of adiponectin correlated significantly with CRP values and ALT values. Leptin plasma concentrations correlated significantly with creatinine values. The results of our study confirm the role of adiponectin, leptin, and resistin in the pathogenesis of psoriasis. Full article

(This article belongs to the Special Issue 10th Anniversary of JCM – New Era in Dermatology)

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Open AccessEditor’s ChoiceArticle

Evaluation of Masticatory Muscles in Adult Patients with Maxillary Hypoplasia Treated with Surgically Assisted Rapid Maxillary Expansion (SARME): A Retrospective Study

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J. Clin. Med. 2023, 12(2), 607; https://doi.org/10.3390/jcm12020607 - 12 Jan 2023

Cited by 1 | Viewed by 782

Abstract

Aim: The aim of the present study was to investigate modifications in electromyographic activity of temporal and masseter muscles before and after surgically assisted rapid maxillary expansion (SARME) in adult subjects. Materials and Methods: Data from 20 patients with unilateral posterior crossbite were [...] Read more.

Aim: The aim of the present study was to investigate modifications in electromyographic activity of temporal and masseter muscles before and after surgically assisted rapid maxillary expansion (SARME) in adult subjects. Materials and Methods: Data from 20 patients with unilateral posterior crossbite were selected retrospectively from the Orthodontics Department of the University of Genoa and the Department of Biomedical Surgical and Dental Sciences of the University of Milan, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico Milan. Inclusion criteria were set as skeletal class I; adult patients (age > 18); good general health; patients with a transverse maxillary deficiency with unilateral posterior crossbite and maxillary constriction ≥ 5 mm; Superficial electromyographic (EMG) examinations at T0 and T1. Exclusion criteria were smoking, metabolic bone diseases (e.g., hyperparathyroidism, vitamin C deficiency), chronic use of corticoids before or during treatment, parafunctional habits (e.g., bruxism), and temporomandibular joint dysfunction. The Shapiro–Wilk test was performed to check whether the data were normally distributed. Differences for each variable before and after SARME were analyzed with a paired t-test (p < 0.05). Results: The statistical analysis demonstrated no statistically significant differences between the EMG values taken before and after SARME regarding the standardized electrical activity of the masticatory muscles (masseter and anterior temporalis (p > 0.05)). Conclusions: Considering the specific conditions of this study, it can be concluded that SARME did not alter the EMG activity of the masseter and temporal muscles. The present study has shown that the masticatory musculature evaluated after approximately 8 months of therapy can adapt well to SARME. Full article

(This article belongs to the Special Issue New Diagnostic, Pharmacological and Therapeutic Trend in Dentistry)

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Open AccessEditor’s ChoiceArticle

SARS-CoV-2 Breakthrough Infections in Health Care Workers: An Italian Retrospective Cohort Study on Characteristics, Clinical Course and Outcomes

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Francesco Paolo Bianchi

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Paolo Boffetta

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Luigi Vimercati

J. Clin. Med. 2023, 12(2), 628; https://doi.org/10.3390/jcm12020628 - 12 Jan 2023

Cited by 2 | Viewed by 735

Abstract

Background: The aim of this study was to determine the characteristics, clinical course and outcomes of COVID-19 breakthrough infections (BIs) among healthcare workers (HCWs) of an Italian University Hospital. Methods: A retrospective observational study was conducted on 6111 HCWs, from January 2021 to [...] Read more.

Background: The aim of this study was to determine the characteristics, clinical course and outcomes of COVID-19 breakthrough infections (BIs) among healthcare workers (HCWs) of an Italian University Hospital. Methods: A retrospective observational study was conducted on 6111 HCWs, from January 2021 to February 2022. The study population was offered the full vaccination with BNT162b2 mRNA COVID-19 vaccine. To allow return to work after BI, the protocol required one negative nasopharyngeal RT-PCR swab followed by a medical examination to assess the HCW’s health status. Laboratory tests, instrumental tests and specialist evaluations were carried out if necessary. Results. The cases of BIs observed numbered 582 (9.7%). The frequency of BIs was significantly higher in females than in males (67% vs. 33%; p = 0.03), and in nurses than in all other professional categories (p = 0.001). A total of 88% of the HCWs affected by BI were still symptomatic after the negative swab. None of the instrumental tests carried out showed any new findings of pathological significance. All cases showed progressive disappearance of symptoms, such that no cases of long COVID and no hospitalization or deaths were recorded. Conclusions. Our results confirm that SARS-CoV-2 infections occur even after a full vaccination course; however, the clinical course is favorable and severe outcomes are reduced. Full article

(This article belongs to the Section Epidemiology & Public Health)

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Open AccessEditor’s ChoiceArticle

Changes in Choroidal Thickness and Structure in Preeclampsia with Serous Retinal Detachment

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J. Clin. Med. 2023, 12(2), 609; https://doi.org/10.3390/jcm12020609 - 12 Jan 2023

Cited by 2 | Viewed by 734

Abstract

Preeclampsia is a pregnancy-specific syndrome characterized by hypertension and proteinuria. We retrospectively investigated the clinical features, including choroidal layer thickness and luminal area to stromal area ratio, in a case series of preeclampsia with serous retinal detachment (SRD). The subjects were pregnant women [...] Read more.

Preeclampsia is a pregnancy-specific syndrome characterized by hypertension and proteinuria. We retrospectively investigated the clinical features, including choroidal layer thickness and luminal area to stromal area ratio, in a case series of preeclampsia with serous retinal detachment (SRD). The subjects were pregnant women with SRD during hospitalization for preeclampsia from October 2014 to June 2021. Based on medical records, affected eyes, time of onset, fundus examination findings, and subfoveal choroidal thickness (SCT), the choroidal layer thickness and choroidal vascular index (CVI) in each patient was examined. Thirteen eyes from seven patients (mean age 30.7 ± 4.7 years) were included in the study. In all cases, SRD improved without topical ocular treatment. The mean SCT at the initial visit was 424.4 ± 70.5 μm, and all patients had choroidal thickening, which significantly decreased to 286.0 ± 57.9 μm (p < 0.01) at the last visit. The mean choroidal inner layer was 162.7 ± 69.4 μm at the initial visit and 122.3 ± 35.5 μm at the final follow-up visit (p = 0.06), showing no significant difference; however, the mean choroidal outer layer was 261.7 ± 47.6 μm at the initial visit and 163.7 ± 37.1 μm at the final follow-up visit (p < 0.01), thus showing a significant decrease. The mean CVI was 67.2 ± 1.3% at the initial visit, yet it had significantly decreased to 65.4 ± 1.1% (p < 0.01) at the final follow-up visit. The findings of this study show that SRD with preeclampsia is associated with increased thickening of the choroidal outer layer, especially in the choroidal luminal area. Full article

(This article belongs to the Collection Recent Advances of Examination and Treatment for Retinal and Choroidal Diseases)

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Open AccessEditor’s ChoiceArticle

Opioid Prescribing for Osteoarthritis: Cross-Sectional Survey among Primary Care Physicians, Rheumatologists, and Orthopaedic Surgeons

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J. Clin. Med. 2023, 12(2), 589; https://doi.org/10.3390/jcm12020589 - 11 Jan 2023

Cited by 1 | Viewed by 790

Abstract

Opioids are often prescribed for osteoarthritis (OA) pain, despite recommendations to limit use due to minimal benefits and associated harms. This study aimed to assess physicians’ practice patterns and perceptions regarding opioids by specialty one year following the Centers for Disease Control and [...] Read more.

Opioids are often prescribed for osteoarthritis (OA) pain, despite recommendations to limit use due to minimal benefits and associated harms. This study aimed to assess physicians’ practice patterns and perceptions regarding opioids by specialty one year following the Centers for Disease Control and Prevention (CDC) published guidance on opioid prescribing. The 139/153 (90.8%) physicians who reported prescribing opioids in the previous year reported decreased prescribing for mild OA (51.3%, 26.5% and 33.3% of primary care physicians, rheumatologists, and orthopaedic surgeons, respectively), moderate OA (50.0%, 47.1% and 48.1%) and severe OA (43.6%, 41.2% and 44.4%). Prescribing changes were attributed to the CDC guidelines for 58.9% of primary care physicians, 59.1% of rheumatologists, and 73.3% of orthopaedic surgeons. Strong opioids were mostly reserved as third-line treatment. Although treatment effectiveness post-CDC guidelines was not assessed, perceptions of efficacy and quality of life with opioids significantly differed across specialties, whereas perceptions of safety, convenience/acceptability and costs did not. Physicians generally agreed on the barriers to opioid prescribing, with fear of addiction and drug abuse being the most important. Across specialties, physicians reported decreased opioid prescribing for OA, irrespective of OA severity, and in most cases attributed changes in prescribing to the CDC guideline. Full article

(This article belongs to the Special Issue Pharmacological Management of Chronic Pain)

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Coagulation Disorders in Sepsis and COVID-19—Two Sides of the Same Coin? A Review of Inflammation–Coagulation Crosstalk in Bacterial Sepsis and COVID-19

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Georgeana Tuculeanu

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Ecaterina Constanta Barbu

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Mihai Lazar

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Cristina Emilia Chitu-Tisu

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Emanuel Moisa

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Silvius Ioan Negoita

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Daniela Adriana Ion

J. Clin. Med. 2023, 12(2), 601; https://doi.org/10.3390/jcm12020601 - 11 Jan 2023

Cited by 2 | Viewed by 1362

Abstract

Sepsis is a major cause of morbidity and mortality worldwide. Sepsis-associated coagulation disorders are involved in the pathogenesis of multiorgan failure and lead to a subsequently worsening prognosis. Alongside the global impact of the COVID-19 pandemic, a great number of research papers have [...] Read more.

Sepsis is a major cause of morbidity and mortality worldwide. Sepsis-associated coagulation disorders are involved in the pathogenesis of multiorgan failure and lead to a subsequently worsening prognosis. Alongside the global impact of the COVID-19 pandemic, a great number of research papers have focused on SARS-CoV-2 pathogenesis and treatment. Significant progress has been made in this regard and coagulation disturbances were once again found to underlie some of the most serious adverse outcomes of SARS-CoV-2 infection, such as acute lung injury and multiorgan dysfunction. In the attempt of untangling the mechanisms behind COVID-19-associated coagulopathy (CAC), a series of similarities with sepsis-induced coagulopathy (SIC) became apparent. Whether they are, in fact, the same disease has not been established yet. The clinical picture of CAC shows the unique feature of an initial phase of intravascular coagulation confined to the respiratory system. Only later on, patients can develop a clinically significant form of systemic coagulopathy, possibly with a consumptive pattern, but, unlike SIC, it is not a key feature. Deepening our understanding of CAC pathogenesis has to remain a major goal for the research community, in order to design and validate accurate definitions and classification criteria. Full article

(This article belongs to the Topic New Advances in Pathophysiology and Therapy of COVID-19 and Other Coronavirus Diseases)

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Open AccessEditor’s ChoiceArticle

Differentiated Effect of Smoking on Disease Activity and Quality of Life among Different Spondyloarthritis Phenotypes

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J. Clin. Med. 2023, 12(2), 551; https://doi.org/10.3390/jcm12020551 - 10 Jan 2023

Cited by 1 | Viewed by 775

Abstract

Background and aims: The effect of smoking on disease activity and quality of life (QoL) in spondyloarthritis (SpA) is far from clear. We aimed to evaluate the relationship between smoking and these outcomes in patients with axial SpA (axSpA) and psoriatic arthritis (PsA). [...] Read more.

Background and aims: The effect of smoking on disease activity and quality of life (QoL) in spondyloarthritis (SpA) is far from clear. We aimed to evaluate the relationship between smoking and these outcomes in patients with axial SpA (axSpA) and psoriatic arthritis (PsA). Patients and methods: This cross-sectional observational multicenter study included 242 patients with axSpA and 90 with PsA. The association between conventional cardiovascular risk factors and disease activity as well as QoL, in both SpA phenotypes was evaluated. For this, univariate and multivariate regression analyses were performed, as well as confirmatory meta-analyses. Results: Regardless of age, sex, or disease duration, patients with axSpA showed significantly less association with obesity (OR 0.50 (0.26–0.96), p = 0.03) and hypertension (OR 0.33 (0.18–0.62), p = 0.0005). However, axSpA was significantly associated with smoking (OR 2.62 (1.36–5.04), p = 0.004). Patients with axSpA were more likely to be in a category of high disease activity compared with PsA (OR 2.86, p = 0.0006). Regardless of sex, age, disease duration, and education level, smoking was significantly associated with higher disease activity in axSpA (OR 1.88, p = 0.027). A fixed-effects model meta-analysis (OR 1.70, p = 0.038) confirmed the association between tobacco and disease activity. No relationship was found between smoking (or other cardiometabolic risk factors) and structural damage or worse QoL in either disease. Conclusions: Although the cardiometabolic risk profile is clearly different between both SpA phenotypes, the only clear link between these factors and increased disease activity was observed between smoking and axSpA. Our findings need further confirmation. Full article

(This article belongs to the Special Issue Clinical Management of Psoriatic Arthritis: Future Perspectives)

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Open AccessEditor’s ChoiceArticle

Sentinel Lymph Node Biopsy in Malignant Melanoma of the Head and Neck: A Single Center Experience

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J. Clin. Med. 2023, 12(2), 553; https://doi.org/10.3390/jcm12020553 - 10 Jan 2023

Cited by 1 | Viewed by 913

Abstract

Purpose: This study evaluated the characteristics of patients with head and neck (H&N) melanoma who underwent sentinel lymph node biopsy (SNLB) and assessed the clinical course of patients categorizing subjects according to SLNB status and melanoma location (scalp area vs. non-scalp areas). Methods: [...] Read more.

Purpose: This study evaluated the characteristics of patients with head and neck (H&N) melanoma who underwent sentinel lymph node biopsy (SNLB) and assessed the clinical course of patients categorizing subjects according to SLNB status and melanoma location (scalp area vs. non-scalp areas). Methods: Patients undergoing SLNB for melanoma of H&N from 2015 to 2021 were prospectively characterized according to sentinel lymph node (SLN) status. SPECT/CT had been previously performed. Patients were followed until the first adverse event to evaluate progression-free survival. Results: 93 patients were enrolled. SLNB was negative in 75 patients. The median Breslow index was higher for patients with positive SLNB compared with patients with negative SLNB. In addition, the Breslow index was higher for melanoma of the scalp compared with non-scalp melanoma. The median follow-up was 24.8 months. Progression occurred at the systemic level in the 62.5% of cases. There was a significant association between positive SLNB and progression (p-value < 0.01) of disease, with lower progression-free survival for patients with melanoma of the scalp compared with those with melanoma at other anatomic sites (p-value: 0.15). Conclusions: Scalp melanomas are more aggressive than other types of H&N melanomas. Sentinel lymph node status is the strongest prognostic criterion for recurrence. Full article

(This article belongs to the Collection Advance in Melanoma)

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Open AccessEditor’s ChoiceReview

Current Therapy and Liver Transplantation for Portopulmonary Hypertension in Japan

by

Katsutoshi Tokushige

,

Tomomi Kogiso

and

Hiroto Egawa

J. Clin. Med. 2023, 12(2), 562; https://doi.org/10.3390/jcm12020562 - 10 Jan 2023

Cited by 1 | Viewed by 795

Abstract

Portopulmonary hypertension (PoPH) and hepatopulmonary syndrome are severe pulmonary complications associated with liver cirrhosis (LC) and portal hypertension. Three key pathways, involving endothelin, nitric oxide, and prostacyclin, have been identified in the development and progression of pulmonary arterial hypertension (PAH). To obtain a [...] Read more.

Portopulmonary hypertension (PoPH) and hepatopulmonary syndrome are severe pulmonary complications associated with liver cirrhosis (LC) and portal hypertension. Three key pathways, involving endothelin, nitric oxide, and prostacyclin, have been identified in the development and progression of pulmonary arterial hypertension (PAH). To obtain a good effect with PAH-specific drugs in PoPH patients, it is important to diagnose PoPH at an early stage and promptly initiate therapy. The majority of therapeutic drugs are contraindicated for Child-Pugh grade C LC, and their effects decrease in the severe PAH stage. Among many LC patients, the measurement of serum brain natriuretic peptide levels might be useful for detecting PoPH. Previously, liver transplantation (LT) for PoPH was contraindicated; however, the indications for LT are changing and now take into account how well the PoPH is controlled by therapeutic drugs. In Japan, new registration criteria for deceased-donor LT have been established for PoPH patients. PoPH patients with a mean pulmonary arterial pressure <35 mmHg and pulmonary vascular resistance <400 dyn/s/cm⁻⁵ are indicated for LT, regardless of whether they are using therapeutic drugs. Combined with PAH-specific drugs, LT may lead to excellent long-term outcomes in PoPH patients. We aimed to review current therapies for PoPH, including LT. Full article

(This article belongs to the Special Issue Liver Cirrhosis: Advances in Clinical Management)

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Open AccessEditor’s ChoiceArticle

A Comparison of Two Forward Head Posture Corrective Approaches in Elderly with Chronic Non-Specific Neck Pain: A Randomized Controlled Study

by

Aisha Salim Al Suwaidi

,

,

,

and

J. Clin. Med. 2023, 12(2), 542; https://doi.org/10.3390/jcm12020542 - 09 Jan 2023

Cited by 1 | Viewed by 4991

Abstract

Forward head posture (FHP) is a common postural displacement that is significantly associated with neck pain, with higher risks of having neck pain in female and older populations. This study investigated the effect of two different forward head posture (FHP) interventions in elderly [...] Read more.

Forward head posture (FHP) is a common postural displacement that is significantly associated with neck pain, with higher risks of having neck pain in female and older populations. This study investigated the effect of two different forward head posture (FHP) interventions in elderly participants with poor posture and non-specific neck pain. Sixty-six elderly participants with a craniovertebral angle (CVA) < 50° were randomized into either a Chiropractic Biophyics^® (CBP^®) or a standardized exercise based FHP correction group (Standard Group). Both groups were treated for 18 sessions over a 6-week period. A 3-month post-treatment follow-up was also assessed with no further interventions. The CBP group received a mirror image^® exercise and a Denneroll™ cervical traction orthotic (DCTO); the standard group performed a protocol of commonly used stretching and strengthening exercises for the neck. Both groups received 30 min of their respective interventions per session. The primary outcome was the CVA, with secondary outcomes including pain intensity, Berg balance score (BBS), head repositioning accuracy (HRA), and cervical range of motion (CROM). After 18 sessions (6 weeks later), the CBP group had statistically significant improvement in the CVA (p < 0.001), whereas the standard group did not. In contrast, both groups showed improved functional measurements on the BBS and HRA as well as improved pain intensity. However, at the 3-month follow-up (with no further treatment), there were statistically significant differences favoring the CBP group for all outcomes (p < 0.001). The differences in the between group outcomes at the 3-month follow-up indicated that the improved outcomes were maintained in the CBP group, while the standard group experienced regression of the initially improved outcomes at 6 weeks. It is suggested that the improvement in the postural CVA (in the CBP group but not in the standard group) is the driver of superior and maintained pain and functional outcomes. Full article

(This article belongs to the Special Issue Spine Rehabilitation in 2022 and Beyond)

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Open AccessEditor’s ChoiceArticle

High Level of Blood Eosinophils and Localization of Bronchiectasis in Patients with Severe Asthma: A Pilot Study

by

Vitaliano Nicola Quaranta

,

,

,

,

,

,

,

,

,

,

,

and

Giovanna Elisiana Carpagnano

J. Clin. Med. 2023, 12(1), 380; https://doi.org/10.3390/jcm12010380 - 03 Jan 2023

Cited by 1 | Viewed by 881

Abstract

Background. Severe asthma and bronchiectasis are heterogeneous diseases that frequently coexist. The location of bronchiectasis is generally determined by specific underlying pathophysiological mechanisms. The aim of this study was to determine whether in a population suffering from both severe asthma and bronchiectasis there [...] Read more.

Background. Severe asthma and bronchiectasis are heterogeneous diseases that frequently coexist. The location of bronchiectasis is generally determined by specific underlying pathophysiological mechanisms. The aim of this study was to determine whether in a population suffering from both severe asthma and bronchiectasis there was a correlation between eosinophilic inflammation and localization of bronchiectasis. Methods. We enrolled 41 patients with coexisting bronchiectasis from eight different severe asthma center outpatient clinics and collected the following data: baseline characteristics, Asthma Control Test, Asthma Control Questionnaire, IgE level, blood count, high-resolution computed tomography and bronchiectasis-related parameters, skin prick test, FeNO50 and flow-volume spirometry. The study was retrospectively registered. Results. The presence of eosinophils > 1000 cells/μL was related to distribution of lower pulmonary bronchiectasis (9.1% upper lobes vs. 53.3% lower lobes, p = 0.014). Indeed, the presence of eosinophilic counts > 1000 increased the probability of lower localization of bronchiectasis compared to upper lobes (ODD 0.088 (0.010–0.772), p = 0.028). Conclusions. An increase in blood eosinophils > 1000 cells/μL seems to be associated with lower preferential localization of bronchiectasis with sparing of the upper lung lobes. This could represent a new potential radiological phenotype that could have a dedicated therapeutic strategy in the future. Full article

(This article belongs to the Special Issue Prevention and Biomarkers of Respiratory Diseases)

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