Diseases, Volume 11, Issue 4 (December 2023) – 53 articles

(1) Background: The evidence indicates that comorbidities are associated with an increase in the risk of death from coronavirus disease 2019 (COVID-19). It is unclear whether such an association is different for various combinations of chronic disease comorbidities. (2) Methods: From 16 March 2020 to 30 November 2021, 104,753 patients with confirmed COVID-19 from Khyber Pakhtunkhwa Province, Pakistan, were studied to determine the association between comorbidities and the duration from symptom onset to death in patients with COVID-19 by stratifying their comorbidity status. (3) Results: The patients with comorbidities had an 84% (OR, 0.16; 95% CI, 0.14 to 0.17) decrease in the duration from symptom onset to death, as opposed to patients without a comorbidity. Among the patients with only one comorbidity, chronic lung disease (OR, 0.06; 95% CI, 0.03 to 0.09) had a greater impact on the duration from symptom onset to death than hypertension (OR, 0.15; 95% CI, 0.13 to 0.18) or diabetes (OR, 0.15; 95% CI, 0.12 to 0.18). The patients with both hypertension and diabetes had the shortest duration (OR, 0.17; 95% CI, 0.14 to 0.20) among the patients with two comorbidities. (4) Conclusions: Comorbidity yielded significant adverse impacts on the duration from symptom onset to death in COVID-19 patients in Pakistan. The impact varied with different combinations of chronic disease comorbidities in terms of the number and type of comorbidities. Full article

Background: Aging is associated with a decrease in muscle mass. Insulin resistance and hyperglycemia accelerate muscle loss, leading to a deterioration in strength, muscle mass, and physical capacity in older adults. This study was conducted to determine the association between sarcopenia and poor glycemic control in older adults with type 2 diabetes mellitus (T2D). Methods: A cross-sectional study was carried out in older adults with T2D in geriatric outpatient clinics. Sarcopenia was diagnosed as per the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. According to glycosylated hemoglobin (HbA1c) levels, participants were classified into glycemic control (HbA1c ≤ 7.5%) and poor glycemic control (HbA1c ≥ 7.5%) groups. Results: Older adults with sarcopenia were found to have poor glycemic control compared to adults without sarcopenia (62.3% vs. 47.9%, p = 0.007). Logistic regression analysis showed an association between poor glycemic control and the presence of sarcopenia (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.17–2.75) and low muscle mass (OR: 1.73, 95% CI: 1.07–2.73). Conclusions: Poor glycemic control is associated with the presence of sarcopenia and low muscle mass, which highlights the need to implement better treatment strategies in order to reduce the loss of muscle mass. Full article

Background: The purpose of this study was to compare the immediate and long-term complications that are associated with the utilized techniques for the insertion of indwelling central venous catheters, that is the open surgical technique, the ultrasound-guided technique, and the transcutaneous technique based on external anatomical landmarks in the right internal jugular vein, to a pediatric population. Methods: This was a prospective randomized trial based on a pediatric patient population under 16 years of age of a tertiary pediatric-oncological hospital. The procedure was performed by a medical team with varying experience regarding the percutaneous and open insertion methods. We studied the outcome of our procedure, based on the immediate and delayed complication rate, as well as the needed time in order to complete the procedure and mean duration of line use. Results: The patients that were inserted in our protocol were divided into three subgroups based on the selected technique for the insertion of the central venous catheter. A total number of 88 insertions (25.4%) (out of 346) were based on the technique that was using external anatomical landmarks, 121 insertions were based on the ultrasound-guided transcutaneous technique (34.9%), whereas in 137 cases (39.5%) the open surgical technique was preferred. All cases that were related to catheter re-insertion were excluded from our study. We performed a statistical analysis regarding the catheter dwell time between the three subgroups of patients and no significant difference was recorded. Moreover, the development of thrombosis was investigated, and we noted that a higher percentage of this complication was related to the transcutaneous external landmark and open surgical technique. Also, the incidence of infection was taken into consideration, which manifested an increased incidence when the transcutaneous technique based on external landmarks was used. Conclusions: Ultrasound-guided percutaneous insertion was considered to be a safe and effective technique for the insertion of central venous catheters. Our study also demonstrated a decrease in operating times when performed by operators with increasing expertise, increased preservation of the diameter of the venous lumen, and no increase in complication rates when the ultrasound-guided technique was selected. Full article

Background: COVID-19 is a modern worldwide pandemic that affected and continues to affect millions of people around the world. Since the discovery that angiotensin-converting enzyme 2 (ACE2) is the binding site for COVID-19 to achieve cell entry, there has been a continuous debate about the effect of COVID-19 infection in first and second trimester abortions. The aim of this review is to investigate the impact of COVID-19 infection on the incidence of miscarriage. Furthermore, we seek to identify potential pathophysiological mechanisms of early pregnancy loss present in infected women. Methods: A literature review was conducted on different databases, including PubMed, Google Scholar, Ovid, Science Direct, Scopus, and Cochrane library, between 1 January 2020 and 31 August 2023. A total of 364 articles were identified and 32 articles were ultimately included in the review. Results: There are several case studies that provide evidence that early pregnancy loss is associated with COVID-19 infection. These findings are not further confirmed by the majority of systematic reviews and meta-analyses, which demonstrate that the total number of miscarriages do not differ significantly between infected and non-infected groups. Furthermore, there are also case reports that associate COVID-19 infection with late second trimester abortions. Conclusions: Given that the virus persists globally, it is important to gain a better understanding of its associated risks in the reproductive process, and larger, more homogeneous, and controlled studies are required to obtain more robust data that can be meta-analyzed to obtain an overview of this potential relationship. Full article

A number of studies have recently demonstrated the effectiveness of CO₂ laser irradiation for the repair and regeneration of scar tissue from injuries or surgical wounds. However, such studies of the oral mucosa are highly limited. Previous studies using CO₂ laser irradiation have indicated that two factors contribute to esthetic healing, namely, artificial scabs, which are a coagulated and carbonized blood layer formed on the wound surface, and photobiomodulation therapy (PBMT) for suppressing wound scarring and promoting wound healing. This review outlines basic research and clinical studies of esthetic healing with the use of a CO₂ laser for both artificial scab formation by high-intensity laser therapy and PBMT in the treatment of injuries and surgical wounds with small parenchymal defects in oral soft tissues. The results showed that the wound surface was covered by an artificial scab, enabling the accumulation of blood and the perfusion necessary for tissue regeneration and repair. Subsequent PBMT also downregulated the expression of transformation growth factor-b1, which is involved in tissue scarring, and decreased the appearance of myofibroblasts. Taken together, artificial scabs and PBMT using CO₂ lasers contribute to the suppression of scarring in the tissue repair process, leading to favorable esthetic and functional outcomes of wound healing. Full article

Background: Considering the large number of patients with pulmonary symptoms admitted to the emergency department daily, it is essential to diagnose them correctly. It is necessary to quickly solve the differential diagnosis between COVID-19 and typical bacterial pneumonia to address them with the best management possible. In this setting, an artificial intelligence (AI) system can help radiologists detect pneumonia more quickly. Methods: We aimed to test the diagnostic performance of an AI system in detecting COVID-19 pneumonia and typical bacterial pneumonia in patients who underwent a chest X-ray (CXR) and were admitted to the emergency department. The final dataset was composed of three sub-datasets: the first included all patients positive for COVID-19 pneumonia (n = 1140, namely “COVID-19+”), the second one included all patients with typical bacterial pneumonia (n = 500, “pneumonia+”), and the third one was composed of healthy subjects (n = 1000). Two radiologists were blinded to demographic, clinical, and laboratory data. The developed AI system was used to evaluate all CXRs randomly and was asked to classify them into three classes. Cohen’s κ was used for interrater reliability analysis. The AI system’s diagnostic accuracy was evaluated using a confusion matrix, and 95%CIs were reported as appropriate. Results: The interrater reliability analysis between the most experienced radiologist and the AI system reported an almost perfect agreement for COVID-19+ (κ = 0.822) and pneumonia+ (κ = 0.913). We found 96% sensitivity (95% CIs = 94.9–96.9) and 79.8% specificity (76.4–82.9) for the radiologist and 94.7% sensitivity (93.4–95.8) and 80.2% specificity (76.9–83.2) for the AI system in the detection of COVID-19+. Moreover, we found 97.9% sensitivity (98–99.3) and 88% specificity (83.5–91.7) for the radiologist and 97.5% sensitivity (96.5–98.3) and 83.9% specificity (79–87.9) for the AI system in the detection of pneumonia+ patients. Finally, the AI system reached an accuracy of 93.8%, with a misclassification rate of 6.2% and weighted-F1 of 93.8% in detecting COVID+, pneumonia+, and healthy subjects. Conclusions: The AI system demonstrated excellent diagnostic performance in identifying COVID-19 and typical bacterial pneumonia in CXRs acquired in the emergency setting. Full article

Right atrial isomerism (RAI) is a complex entity with varying diagnostic and treatment outcomes due to its rarity. Treatment options range from palliative to corrective surgeries, resulting in heterogeneous outcomes. The aim of this study was to analyze the results obtained after cardiac surgery in patients with RAI. A retrospective study was conducted, including patients diagnosed with RAI who underwent cardiac surgery. Their follow-up was from 1 January 2010 to 31 March 2020. Demographic characteristics and perioperative conditions were described. Thirty-eight patients were included, the median age was 4 years (IQR 2–9.2) and 57.9% were men. The main diagnoses were atrioventricular canal (63.2%) and pulmonary stenosis (55.3%). The most common surgical procedures were modified Blalock–Taussig shunt (65.8%) and total cavopulmonary connection with an extracardiac conduit fenestrated without cardiopulmonary bypass (15.9%). We did not find any factors associated with negative outcomes in these patients. The overall survival was 86.8%, with a better outcome in those who did not require reintubation (log rank, p < 0.01). The survival of RAI was similar to other centers. Individuals with RAI should be evaluated rigorously to determine an adequate repair strategy, considering high morbidity and mortality. Full article

(1) Background: The erythrocyte sedimentation rate (ESR) is widely diffused in hematology laboratories to monitor inflammatory statuses, response to therapies (such as antibiotics), and oncologic diseases. However, ESR is not a specific diagnostic marker but needs to be contextualized and compared with clinical and other laboratory findings. This study aimed to investigate the performance of two automated instruments, namely the DIESSE CUBE 30 TOUCH (DIESSE, Siena, Italy) and the Alifax Test 1 (Alifax Srl, Polverara, Italy), in comparison with the gold standard, the Westergren method, in lymphoproliferative and myeloproliferative patients. (2) Methods: 97 EDTA samples were selected from the hematology department of Roma Tor Vergata Hospital and analyzed. Statistical analysis was applied. (3) A good correlation between CUBE 30 TOUCH and the gold standard was observed in the overall sample (R² = 0.90), as well as in patients with lymphoproliferative diseases (R² = 0.90) and myeloproliferative diseases (R² = 0.90). The correlation between Test 1 and the gold standard was observed in the overall sample (R² = 0.68), as well as in patients with lymphoproliferative diseases (R² = 0.79) and myeloproliferative diseases (R² = 0.53). (4) Conclusions: The CUBE 30 TOUCH appears to be a more trustworthy tool for evaluating ESR in these pathologies. Full article

Background: The objective of this study was to conduct a comparative evaluation of the effectiveness of ezetimibe in combination with statins or statin monotherapy in patients with hypercholesterolemia in a real-world setting. Methods: It was a retrospective multicenter observational study conducted in Russia. We included patients who received statins or a combination of statins with ezetimibe for ≥3 months. The primary endpoint of this study was the frequency of achieving low-density lipoprotein cholesterol (LDL-C) goal levels at the time of enrollment in the study (%). Results: The full analysis set consisted of 1000 patients: 250 subjects in the statin monotherapy group and 750 subjects in the combination group. The groups did not differ in clinical, demographic, or laboratory variables, except for a higher prevalence of hypertension and higher baseline lipid values in the statin monotherapy group. During treatment, the LDL-C concentration decreased by 1.10 ± 1.04 mmol/L (change of −27.5 ± 28.5% from baseline) in the statin monotherapy group and by 1.55 ± 1.17 mmol/L (change of −38.2 ± 25.6% from baseline) in the combination therapy group, p < 0.001. The target LDL-C level was achieved in 22.4% of the patients in the monotherapy group compared with 28.8% of the patients in the combination therapy group, p = 0.049. Conclusions: In real-world clinical practice, statin/ezetimibe combination therapy demonstrated a more frequent achievement of target LDL-C levels compared with statin monotherapy. The addition of ezetimibe to statin therapy increased the probability of achieving LDL-C level goals by 29%. Full article

POEMS syndrome—characterized by polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes—is an uncommon and complex paraneoplastic disorder encompassing a diverse array of symptoms. Here we report the challenging case of a 34-year-old female who sought medical attention at the emergency department due to distal lower limb weakness. She was breastfeeding her first child at that time. Her condition rapidly deteriorated, making it difficult for her to perform simple tasks independently. Initially, she struggled with activities like jumping or climbing stairs. Eventually, her ability to walk was also compromised. These symptoms underscored the swift evolution of her polyneuropathy. Nerve conduction studies and electromyography confirmed a diagnosis of mixed demyelinating and axonal polyneuropathy. Subsequent investigations, including bone marrow biopsy and immunochemistry testing, revealed a plasma cell disorder characterized by lambda monoclonal gammopathy, along with elevated levels of vascular endothelial growth factor (VEGF > 8000 pg/mL). This pivotal finding led to the diagnosis of POEMS syndrome, prompting the initiation of antineoplastic therapy (daratumumab-lenalidomide-dexamethasone) to manage this condition. An autologous cell transplantation was planned. The rarity of POEMS syndrome and its diverse clinical manifestations often lead to an incorrect or delayed diagnosis. Our case underscores the importance of considering this syndrome in patients presenting with acute or subacute polyneuropathy, even if the patients are young. In conclusion, this case elucidates the diagnostic complexities of POEMS syndrome, emphasizing the integral role of comprehensive multidisciplinary evaluations and the potential influence of increased VEGF as a diagnostic key element and possible therapeutic target. Full article

Special populations, particularly pregnant women, are uniquely susceptible to infectious diseases due to alterations in their immunological, respiratory, and cardiovascular systems during gestation. Influenza infections during the perinatal period have been associated with more severe maternal and perinatal outcomes, underscoring the critical importance of vaccination data for pregnant women. According to the World Health Organization (WHO), all pregnant women and those of childbearing age should receive the inactivated influenza vaccine, irrespective of their pregnancy stage. This study aimed to elucidate factors influencing neonatal antibody presence following maternal influenza vaccination. Conducted through convenience sampling in Athens, Greece, this study involved 78 pregnant women who received flu vaccinations. The participants completed questionnaires covering demographics, obstetric history, attitudes toward influenza vaccination, and knowledge about the influenza virus and pregnancy vaccination. Blood samples were collected from 83 neonates to assess IgG antibody presence. Five of the surveyed women had twin pregnancies. The statistical analysis employed IBM SPSS-Statistics version 26.0. This study revealed the presence of positive influenza A and B antibodies in neonates following maternal immunization. Furthermore, it identified factors such as the gestational week and timing of vaccination during pregnancy that influenced the transfer of antibodies from mother to fetus. These findings offer valuable insights for healthcare professionals to provide informed recommendations on influenza vaccination during pregnancy and empower expectant mothers to make informed decisions about the benefits of immunization. Full article

Background: The COVID-19 pandemic has led to unfavorable disruptions to daily living routines by exerting deleterious effects on several aspects of human mental and physical health and quality of life worldwide. The purpose of the current survey is to explore the potential association of COVID-19 infection with multiple sociodemographic, anthropometric, and lifestyle factors of community-dwelling older adults. Methods: This is a cross-sectional survey including 5197 older adults aged over 65 years old from 10 geographically diverse regions of Greece. Relevant questionnaires were used to record study the population sociodemographic factor, while anthropometric parameters were also measured. Validated questionnaires were also applied to assess several lifestyle factors such as depression, anxiety, stress, cognitive status, sleep quality, health-related quality of life, physical activity levels, and Mediterranean diet (MD) adherence. Results: In multivariate regression analysis, COVID-19 infection was significantly, independently related with urban residence (p = 0.0107), regular smoking (p = 0.0218), overweight status and obesity (p = 0.0036), as well as abdominal obesity (p = 0.0008), higher risk of depression (p = 0.0027), anxiety (p = 0.0045), stress (p = 0.0038), inadequate sleep quality (p = 0.0108), lower physical activity levels (p = 0.0012), reduced MD compliance (p = 0.0009), and poor health-related quality of life (p = 0.0002). In univariate analysis, older adults’ age (p = 0.0001), male gender (p = 0.0015), living alone (p = 0.0023), lower educational and economic level (p = 0.0175 and p = 0.0294, respectively), and cognition decline (p = 0.0032) were also related with the presence of COVID-19 infection; however, these associations were considerably attenuated at a non-significant level by adjustment for several confounders in multivariate analysis. Conclusions: This is one of the few available studies supporting evidence that COVID-19 infection may be associated with diverse sociodemographic, anthropometric, and lifestyle factors in an older adults’ population in Greece. This study highlights the strong demand to provide psychological and nutritional counselling and support to older adults diagnosed with COVID-19 infection in order to ameliorate disease symptoms and severity, emphasizing the adaptation of healthy dietary and lifestyle habits as preventing and supplementary therapeutic factors against COVID-19. Full article

Rheumatoid arthritis (RA) is associated with high cardiovascular mortality. It is not clear whether the metabolic consequences of chronic inflammation are involved. Biological disease-modifying anti-rheumatic drugs (bDMARDs) are highly efficient in the treatment of inflammation in RA. In this study, we aimed to describe the metabolic effects of anti-TNF-α treatment in RA patients. The clinical status of 16 patients was assessed using disease activity score-28 (DAS28) and C-reactive protein (CRP). Plasma samples were collected before treatment with anti-TNF-α treatment as well as after three and six months of treatment. Markers of lipid and glucose metabolism, as well as renal biomarkers, were assessed using standard biochemistry. ELISA was used for the quantification of insulin, leptin, and adiponectin. Although fasting insulin decreased by 14% at the end of the study, most of the analyzed parameters did not show any statistically or clinically significant dynamics. The exception was total bilirubin and cholesterol, which increased by 53% and 14%, respectively, after six months of treatment with anti-TNF-α treatment. Anti-TNF-α treatment did not induce major metabolic changes despite the strong anti-inflammatory and clinical symptoms of RA. Further studies will show whether longer observations are required for the detection of the metabolic effects of the anti-inflammatory treatment. Additional research is needed to understand the observed effect of bilirubin as an important endogenous antioxidant. Full article

Prolonged COVID is a persistent condition following the initial COVID-19 infection, which is characterized by a variety of symptoms that may include fatigue, muscle pain, sleep disturbances, “brain fog”, respiratory, cardiovascular, digestive, neurological and dermatological symptoms. Physical therapy has been identified as a crucial aspect of the management of patients with long COVID, as it can help improve symptoms and overall physical function. The investigation of long COVID poses significant challenges due to the diversity and variability of symptoms, lack of clear diagnostic criteria, and limited understanding of the underlying mechanisms. The aim of this study is to conduct a systematic review of studies conducted in patients with long COVID in conjunction with interventions targeting respiratory function, particularly involving physical activity. To this end, we conducted a systematic review to analyze studies conducted on treatment programs for long COVID based on some form of physical activity. The protocol of the review was registered in the PROSPERO website, and the databases PubMed, Scopus, CINAHL and WOS were searched. Of the 62 initial articles, six were included in the review. The results obtained have positive implications for the advancement of physical activity as a therapeutic intervention for individuals with long COVID-19 and the conceptualization of evidence-based treatment protocols. Statistically significant results have been observed in studies of at least 6 weeks duration, in which inspiratory muscle training exercises are proposed. Further research is needed to better understand long COVID and develop effective treatment strategies. Full article

Chromoblastomycosis (CBM) is a neglected human disease, caused by different species of pigmented dematiaceous fungi that cause granulomatous and suppurative dermatosis. This infection is difficult to treat and there are limited therapeutic options, including terbinafine, itraconazole, and tioconazole. Classic treatment is administered for a long period of time, but some patients do not respond properly, and therefore, such therapeutic approaches possess low cure rates. Therefore, it is vital to develop new strategies for the treatment of CBM. In this regard, it has been observed that the association of immunomodulatory molecules such as glucan with therapy carried out with antifungal drugs improves cutaneous lesions in comparison to treatment with antifungal drugs alone, suggesting that drug association may be an interesting and significant approach to incorporate into CBM therapy. Thus, the aim of this work was to associate classical antifungal therapy with the adjuvants imiquimod and acitretin. In the present case, we reported a patient with extensive CBM caused by Fonsaecae pedrosoi, that affected an extensive area of the right leg, that was left without treatment for 11 years. He was treated with a classical combination of itraconazole and terbinafine via the oral route plus topical imiquimod and oral acitretin, as an adjuvant therapy. After five months of treatment, a significant regression of verrucous plaques was observed, suggesting that the use of these adjuvants combined with the classical antifungal drugs, intraconazole plus terbinafine, can reduce treatment time and rapidly improve the patient’s quality of life. This result confirms that the use of coadjuvant drugs may be effective in the treatment of this infectious disease. Full article

We describe two cases of thalassemia intermedia (TI) patients with the presence of Gaucher-like cells in hematopoietic tissue biopsies, raising diagnostic dilemmas. The first is a 56-year-old female with bone lesions, splenomegaly, hypochromic microcytic anemia and Gaucher-like cells in the bone marrow, with a final diagnosis of TI, and the second is a 69-year-old male with TI, monoclonal gammopathy of undetermined significance (MGUS) that accelerated to multiple myeloma (MM) requiring treatment, bone disease and Gaucher-like cells in the bone marrow and the spleen, and heterozygoty of Gaucher disease (GD). Gaucher-like cells are difficult to differentiate from true Gaucher cells, that are the hallmark of GD suspicion. These cells are usually reported in the lymphohematopoietic system. They have been described in myeloproliferative disorders, hematological malignancies, infectious diseases, hemoglobinopathies and other hemolytic anemias. The presence of Gaucher-like cells in patients with thalassemia major has been well documented, whereas there are limited references regarding cases with thalassemia intermedia. The identification of these cells in thalassemia probably reflects the high cell turnover. The bony complications in GD and TIare not yet fully explained in the literature, and this raises the question of whether Gaucher-like cells could play a pathogenetic role in the bone disease of thalassemia, as Gaucher cells are considered to play a similar role in bone complications of GD. Moreover, given the rarity and similarity of Gaucher and Gaucher-like cells, we would like to highlight that the presence of Gaucher-like cells in the bone marrow should not be overlooked, as they might be obscuring an underlying pathology, in order to ensure that hematologists, internists and hematopathologists will be promptly and accurately diagnosed. Full article

Staphylococcus aureus (S. aureus) is a common pathogen involved in community- and hospital-acquired infections. Its biofilm formation ability predisposes it to device-related infections. Methicillin-resistant S. aureus (MRSA) strains are associated with more serious infections and higher mortality rates and are more complex in terms of antibiotic resistance. It is still controversial whether MRSA are indeed more virulent than methicillin-susceptible S. aureus (MSSA) strains. A difference in biofilm formation by both types of bacteria has been suggested, but how only the presence of the SCCmec cassette or mecA influences this phenotype remains unclear. In this review, we have searched for literature studying the difference in biofilm formation by MRSA and MSSA. We highlighted the relevance of the icaADBC operon in the PIA-dependent biofilms generated by MSSA under osmotic stress conditions, and the role of extracellular DNA and surface proteins in the PIA-independent biofilms generated by MRSA. We described the prominent role of surface proteins with the LPXTG motif and hydrolases for the release of extracellular DNA in the MRSA biofilm formation. Finally, we explained the main regulatory systems in S. aureus involved in virulence and biofilm formation, such as the SarA and Agr systems. As most of the studies were in vitro using inert surfaces, it will be necessary in the future to focus on biofilm formation on extracellular matrix components and its relevance in the pathogenesis of infection by both types of strains using in vivo animal models. Full article

Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that causes significant dysfunction in individuals. Currently, there are many approved pharmacotherapy and psychotherapy treatment options for PTSD, but unfortunately, half of the patients do not respond to traditional therapies. In this article, we review clinical trials and research on 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in PTSD patients, its pharmacokinetics, and current treatment guidelines for PTSD. Our findings are based on the results of the efficacy of MDMA-assisted psychotherapy from six phase II randomized controlled trials. MDMA-assisted psychotherapy for PTSD has received the “breakthrough therapy” designation from the FDA. MDMA can reduce PTSD symptoms even in treatment-resistant cases by increasing certain neurohormones, i.e., dopamine, serotonin, norepinephrine, and oxytocin. It also modulates activities in the brain regions involved in fear and anxiety. Future research is needed to show whether the advantages outweigh the disadvantages and whether its use can be integrated into available treatment options for PTSD. Full article

A balanced diet is achieved not only via the consumption of a variety of food products but also by ensuring that we take in sufficient quantities the micronutrients necessary for the adequate functioning of the human body, such as vitamins, an important one of which is vitamin D. Vitamin D has been closely linked to bone health. Vitamin D deficiency has often been associated with negative effects concerning several pregnancy adverse outcomes, the most important of which are the birth of SGA newborns, premature birth, and, finally, preeclampsia, which are discussed in this work. The aim of this review is to critically summarize and scrutinize whether the concentration of vitamin D in the blood serum of pregnant women in all its forms may be correlated with the risk of preeclampsia during pregnancy and whether vitamin D levels could act both as a protective agent or as a risk factor or even a prognostic measure of the disease. The association of vitamin D levels with the onset of preeclampsia was examined by searching the PubMed and Google Scholar databases. A total of 31 clinical trials were identified and included in this review, with the aim of summarizing the recent data concerning vitamin D levels and the risk of preeclampsia. Among them, 16 were published in the last five years, and 13 were published within the last a decade. Most studies showed a significant association between vitamin D deficiency and preeclampsia risk. It was also found that the higher the dose, the lower the risk of disease. Of the 31 articles, only 7 of them did not show a significant difference between vitamin D levels and preeclampsia regardless of comorbidity. The results of this review suggest that there is indeed an association between the concentration of vitamin D during pregnancy and the risk of preeclampsia; however, further studies are strongly recommended to derive conclusive evidence. Full article

Surgery is one of the most energy-intensive branches of healthcare. Although the COVID-19 pandemic has reduced surgical volumes, infection control protocols have increased the ecological footprint of surgery owing to the extensive use of personal protective equipment, sanitation, testing and isolation resources. The burden of environmental diseases requiring surgical care, the international commitment towards environmental sustainability and the global efforts to return to the pre-pandemic surgical workflow call for action towards climate-friendly surgery. The authors have searched the peer-reviewed and gray literature for clinical studies, reports and guidelines related to the ecological footprint of surgical care and the available solutions and frameworks to reduce it. Numerous studies concede that surgery is associated with a high rate of energy utilization and waste generation that is comparable to major non-medical sources of pollution. Recommendations and research questions outlining environmentally sustainable models of surgical practices span from sanitation and air quality improvement systems to the allocation of non-recyclable consumables and energy-efficient surgical planning. The latter are particularly relevant to infection control protocols for COVID-19. Paving the way towards climate-friendly surgery is a worthy endeavor with a major potential to improve surgical practice and outcomes in the long term. Full article

Uterine leiomyomas are the most common benign tumors in women of childbearing age. They may lead to problems of conception or complications during the gestational period. The methods of treatment include surgical (myomectomy and hysterectomy, embolization of arteries) and therapeutic treatment (ulipristal acetate, leuprolide acetate, cetrorelix, goserelin, mifepristone). Both approaches are efficient but incompatible with pregnancy planning. Therefore, there is a call for medical practice to develop therapeutical means of preventing leiomyoma onset in patients planning on becoming pregnant. Based on the analysis of GWAS data on the search for mononucleotide polymorphisms associated with the risk of leiomyoma, in meta-transcriptomic and meta-methylomic studies, target proteins have been proposed. Prospective therapeutic treatments of leiomyoma may be based on chemical compounds, humanized recombinant antibodies, vaccines based on markers of the uterine leiomyoma cells that are absent in the adult organism, or DNA and RNA preparations. Three different nosological forms of the disease associated with driver mutations in the MED12, HMGA2, and FH genes should be considered when developing or prescribing drugs. For example, synthetic inhibitors and vaccines based on matrix metalloproteinases MMP11 and MMP16 are expected to be effective only for the prevention of the occurrence of MED12-dependent nodules. Full article

Hypertensive disorders of pregnancy (HDP), comprising gestational hypertension (GH) and pre-eclampsia (PE), are leading causes of maternal and perinatal morbidity and mortality. Both GH and PE are characterized by new-onset hypertension, but PE additionally includes proteinuria and/or end-organ damage. Impaired nitric oxide (NO) bioavailability may lead to endothelial dysfunction in GH and PE, and the primary source of vascular NO is endothelial NO synthase (eNOS). However, no previous study has investigated plasma eNOS concentrations in patients with GH and PE. In this study, we compared plasma eNOS concentrations in healthy pregnancies and HDP in two independent cohorts. The primary study included 417 subjects, with 43 non-pregnant (NP) and 156 healthy pregnant (HP) women and 122 patients with GH and 96 with PE. The replication study included 85 pregnant women (41 healthy and 44 pre-eclamptic). Plasma concentrations of eNOS were measured using a commercial ELISA kit provided by R&D Systems, and plasma nitrite concentrations were assessed using two ozone-based chemiluminescence assays. Correlations between plasma eNOS concentrations and plasma nitrite concentrations, as well as clinical and biochemical parameters, were evaluated by either Spearman’s or Pearson’s tests. In the primary study, NP women and HDP had significantly lower plasma eNOS concentrations compared to HP; concentrations were even lower in PE compared to GH. Plasma eNOS concentrations were reduced but not significant in early-onset PE, PE with severe features, preterm birth, and intrauterine growth restriction. No correlation was observed between plasma eNOS and nitrite levels. In HDP, there was a significant positive correlation between levels of eNOS and hemoglobin (r = 0.1496, p = 0.0336) as well as newborn weight (r = 0.1487, p = 0.0316). Conversely, a negative correlation between eNOS levels and proteinuria was observed (r = −0.2167, p = 0.0179). The replication study confirmed significantly reduced plasma concentrations of eNOS in PE compared to HP. Our findings provide evidence of reduced plasma eNOS concentrations in HDP; they were particularly lower in PE compared to GH and HP in two independent studies. Full article

Introduction: Type 2 diabetes mellitus (T2DM) patients are at high risk of dyslipidemia, which in turn is associated with macrovascular diseases, such as heart diseases and stroke, and microvascular diseases, such as neuropathy and nephropathy. There are contradictory findings in the literature regarding the relationship between glycated hemoglobin (HbA1c) and the lipid profile among T2DM patients. This study was performed to investigate the association between HbA1c level and the lipid profile in elderly T2DM patients at a primary care hospital in Jeddah City, Saudi Arabia. Methods: This study is a retrospective cross-sectional study conducted at the Prince Abdul Majeed Healthcare Center (PAMHC) in Jeddah, Saudi Arabia. The sociodemographic and clinical data of the T2DM patients who had visited the PAMHC from 1 January 2020 to 31 December 2021, were collected from the data registry of the PAMHC and analyzed for publication. Results: The study included a total of 988 T2DM patients (53.3% male). Of the participants, 42.9% were aged between 55 and 64 years. Dyslipidemia parameters were presented as high LDL-c (in 60.3% cases), low HDL-c (in 39.8% cases), high triglycerides (in 34.9% cases), and high total cholesterol (in 34.8% cases). The correlation of HbA1c with total cholesterol (TC) and triglycerides (TGs) was positively significant, thereby highlighting the important link between glycemic control and dyslipidemia. A mean increase of 4.88 mg/dL and 3.33 mmHg in TG level and diastolic blood pressure, respectively, was associated with the male gender, in comparison to the female gender. However, the male gender was significantly associated with the reduction in the mean cholesterol level, BMI, HbA1c, HDL-c, and LDL-c by 11.49 mg/dL, 1.39 kg/m², 0.31%, 7.47 mg/dL, and 5.6 mg/dL, respectively, in comparison to the female gender. Conclusions: The results of this study show that HbA1c was significantly associated with cholesterol and triglyceride levels in the T2DM patients included in the study. Our findings highlight the important relationship between glycemic control and dyslipidemia. Full article

Leishmaniasis is a neglected tropical illness with a wide variety of clinical signs ranging from visceral to cutaneous symptoms, resulting in millions of new cases and thousands of fatalities reported annually. This article provides a bibliometric analysis of the main authors’ contributions, institutions, and nations in terms of productivity, citations, and bibliographic linkages to the application of nanoparticles (NPs) for the treatment of leishmania. The study is based on a sample of 524 Scopus documents from 1991 to 2022. Utilising the Bibliometrix R-Tool version 4.0 and VOSviewer software, version 1.6.17 the analysis was developed. We identified crucial subjects associated with the application of NPs in the field of antileishmanial development (NPs and drug formulation for leishmaniasis treatment, animal models, and experiments). We selected research topics that were out of date and oversaturated. Simultaneously, we proposed developing subjects based on multiple analyses of the corpus of published scientific literature (title, abstract, and keywords). Finally, the technique used contributed to the development of a broader and more specific “big picture” of nanomedicine research in antileishmanial studies for future projects. Full article

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition with fewer treatments available as the severity increases. Previous systematic reviews have demonstrated the benefits of long-term macrolide use. However, the therapeutic differences between different macrolides and the optimal duration of use remain unclear. Methods: A systematic review and meta-analysis were conducted to assess the effectiveness of long-term macrolide use in reducing COPD exacerbations, compare the therapeutic differences among macrolides, and determine the appropriate treatment duration. Four databases (PubMed, Cochrane Library, Web of Science, and ICHU-SHI) were searched until 20 March 2023, and a random-effects model was used to calculate the pooled effect. Results: The meta-analysis included nine randomized controlled trials involving 1965 patients. The analysis revealed an odds ratio (OR) of 0.34 (95% confidence interval [CI] 0.19, 0.59, p < 0.001) for the reduction in exacerbation frequency. Notably, only azithromycin or erythromycin showed suppression of COPD exacerbations. The ORs for reducing exacerbation frequency per year and preventing hospitalizations were −0.50 (95% CI: −0.81, −0.19; p = 0.001) and 0.60 (95% CI: 0.3, 0.97; p = 0.04), respectively. Statistical analyses showed no significant differences between three- and six-month macrolide prescriptions. However, studies involving a twelve-month prescription showed an OR of 0.27 (95% CI: 0.11, 0.68; p = 0.005; I² = 81%). Although a significant improvement in St George’s Respiratory Questionnaire (SGRQ) total scores was observed with a mean difference of −4.42 (95% CI: −9.0, 0.16; p = 0.06; I² = 94%), the minimal clinically important difference was not reached. While no adverse effects were observed between the two groups, several studies have reported an increase in bacterial resistance. Conclusions: Long-term use of azithromycin or erythromycin suppresses COPD exacerbations, and previous studies have supported the advantages of a 12-month macrolide prescription over a placebo. Full article

Ventilator-associated pneumonia (VAP) has significant effects on patient outcomes, including prolonging the duration of both mechanical ventilation and stay in the intensive care unit (ICU). The aim of this study was to assess the association between non-invasive ventilation/oxygenation (NIVO) prior to intubation and the rate of subsequent VAP. This was a multicenter retrospective cohort study of adult patients who were admitted to the medical ICU from three tertiary care academic centers in three distinct regions. NIVO was defined as continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), or high-flow nasal cannula (HFNC) for any duration during the hospitalization prior to intubation. The primary outcome variable was VAP association with NIVO. A total of 17,302 patients were included. VAP developed in 2.6% of the patients (444/17,302), 2.3% (285/12,518) of patients among those who did not have NIVO, 1.6% (30/1879) of patients who had CPAP, 2.5% (17/690) of patients who had HFNC, 8.1% (16/197) of patients who had BiPAP, and 4.8% (96/2018) of patients who had a combination of NIVO types. Compared to those who did not have NIVO, VAP was more likely to develop among those who had BiPAP (adj OR 3.11, 95% CI 1.80–5.37, p < 0.001) or a combination of NIVO types (adj OR 1.91, 95% CI 1.49–2.44, p < 0.001) after adjusting for patient demographics and comorbidities. The use of BiPAP or a combination of NIVO types significantly increases the odds of developing VAP once receiving IMV. Full article

The search for new antimicrobial agents is a continuous struggle, mainly because more and more cases of resistant strains are being reported. Mycobacterium tuberculosis (MTB) is the main microorganism responsible for millions of deaths worldwide. The development of new antimicrobial agents is generally aimed at finding strong interactions with one or more bacterial receptors. It has been proven that bacteriophages have the ability to adhere to specific and selective regions. However, their transport and administration must be carefully evaluated as an excess could prevent a positive response and the bacteriophages may be eliminated during their journey. With this in mind, the mycobacteriophage D29 was encapsulated in nanoliposomes, which made it possible to determine its antimicrobial activity during transport and its stability in the treatment of active and latent Mycobacterium tuberculosis. The antimicrobial activity, the cytotoxicity in macrophages and fibroblasts, as well as their infection and time–kill were evaluated. Phage nanoencapsulation showed efficient cell internalization to induce MTB clearance with values greater than 90%. Therefore, it was shown that nanotechnology is capable of assisting in the activity of degradation-sensitive compounds to achieve better therapy and evade the immune response against phages during treatment. Full article

This study investigates the clinical and pathological outcomes of preoperative balloon-occluded transcatheter arterial chemoembolization (B-TACE) in patients with single hepatocellular carcinoma (HCC). The data are from 25 consecutive patients who underwent sequential treatment of subsegmental B-TACE and hepatic surgery for single HCC. Radiological and pathological evaluation of oily subsegmentectomy, defined as the iodized oil-laden necrotic area that includes the entire HCC and surrounding liver parenchyma, were performed. Subsegmental B-TACE was technically successful in all patients. The major and minor complication rates were 8% and 24%, respectively. On the first follow-up computed tomography (CT), oily subsegmentectomy was observed in 18 (72%) out of 25 patients. Apart from one patient showing a partial response, the remaining 24 (96%) patients showed a complete response. Pathological complete necrosis of the HCC was observed in 18 (72%) out of 25 patients with complete or extensive necrosis of the peritumoral liver parenchyma. The remaining seven patients without peritumoral parenchymal necrosis had extensive necrosis of the HCCs. In conclusion, preoperative B-TACE can be a safe and effective method for the treatment of single HCC and a good bridge treatment for subsequent surgical resection. In addition, oily subsegmentectomy itself on the CT can be a good predictor of pathological complete necrosis of the HCC. The findings obtained from this study would provide a potential role of B-TACE in the treatment strategy for single HCC. Full article

Worldwide, colon cancer is the third most frequent malignancy and the second most common cause of death. Although it can strike anybody at any age, colon cancer mostly affects the elderly. Small, non-cancerous cell clusters inside the colon, commonly known as polyps, are typically where colon cancer growth starts. But over time, if left untreated, these benign polyps may develop into malignant tissues and develop into colon cancer. For the diagnosis of colon cancer, with routine inspection of the colon region for polyps, several techniques, including colonoscopy and cancer scanning, are used. In the case identifying the polyps in the colon area, efforts are being taken to surgically remove the polyps as quickly as possible before they become malignant. If the polyps become malignant, then colon cancer treatment strategies, such as surgery, chemotherapy, targeted therapy, and immunotherapy, are applied to the patients. Despite the recent improvements in diagnosis and prognosis, the treatment of colorectal cancer (CRC) remains a challenging task. The objective of this review was to discuss how CRC is initiated, and its various developmental stages, pathophysiology, and risk factors, and also to explore the current state of colorectal cancer diagnosis and treatment, as well as recent advancements in the field, such as new screening methods and targeted therapies. We examined the limitations of current methods and discussed the ongoing need for research and development in this area. While this topic may be serious and complex, we hope to engage and inform our audience on this important issue. Full article

Background: Dasatinib, nilotinib, and sorafenib are clinically proven tyrosine kinase inhibitors (TKIs) used for the treatment of leukemia and hepatocellular carcinoma. However, there is a growing concern regarding cardiotoxicity associated with their use. The impact of these TKIs on vascular smooth muscle cells (VSMCs) remains unexplored. This study aims to investigate the effects of TKIs on VSMC proliferation and migration, as well as to elucidate the underlying mechanisms involving inflammatory and apoptotic pathways. Methods: VSMCs were extracted from albino rats and cultured in vitro. The cells were divided into four experimental groups: control, dasatinib, sorafenib, and nilotinib. The MTT assay was employed to assess the cytotoxic effects of TKIs on VSMCs. A scratch assay was conducted to evaluate the inhibitory potential of TKIs on VSMC migration. Flow cytometry analysis was used to detect apoptotic cells. Real-Time PCR expression was utilized to determine the differential gene expression of apoptotic and inflammatory markers. Results: Dasatinib, nilotinib, and sorafenib demonstrated significant inhibitory effects on VSMC viability and migration at low concentrations (<1 µmol/L, p < 0.05). Furthermore, gene expression analysis revealed up-regulation of inflammatory biomarkers (TNF-α, IL-6, and IL-1β) and apoptotic markers (P53, BAX), along with down-regulation of the anti-apoptotic biomarker BCL-2 in response to all TKIs. Conclusions: This study demonstrates that dasatinib, nilotinib, and sorafenib inhibit VSMC proliferation and migration, suggesting their potential to induce vascular injury and remodeling by activating inflammation and apoptosis pathways. These findings highlight the need for further investigation into the cardiotoxic effects of these TKIs and the development of strategies to mitigate their adverse vascular effects. Full article