Med. Sci., Volume 11, Issue 2 (June 2023) – 19 articles

The present study evaluated the effectiveness and safety of corneal collagen cross-linking (CXL). A total of 886 eyes with progressive keratoconus were enrolled in a retrospective cohort study in a tertiary care university hospital. CXL was performed using a standard epithelium-off Dresden protocol. Visual outcomes, maximum keratometry (Kmax), demarcation line measurements, and complications were recorded. Visual outcomes and keratometric data were analyzed in a subgroup comprising 610 eyes. Uncorrected distance visual acuity (UDVA) improved from 0.49 ± 0.38 LogMAR to 0.47 ± 0.39 LogMAR (p = 0.03, n = 610) three years after the procedure, while corrected distance visual acuity (CDVA) improved from 0.15 ± 0.14 LogMAR to 0.14 ± 0.15 LogMAR (p = 0.007, n = 610). A significant reduction of Kmax from 56.28 ± 6.10 to 54.98 ± 6.19 (p < 0.001, n = 610) was observed three years after CXL. In five eyes (0.82%, 5/610) keratoconus progression continued after CXL. Three eyes were retreated successfully with documented refractive and topographic stability after five years. In the 35 eyes that completed 10 years of follow-up, mean visual acuity and topographic parameters remained stable. In conclusion, CXL is a safe and effective treatment for avoiding keratoconus progression. Long-term data are encouraging, supporting a high safety profile for this procedure. Full article

Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies, involving the oral cavity, pharynx, hypopharynx, larynx, nasal cavity, and salivary glands, that together compose the seventh most common cancer diagnosis worldwide. With 890,000 new cases and 450,000 deaths annually per GLOBOCAN estimates, HNSCC accounts for roughly 4.5% of cancer diagnoses and deaths. In the developing world, the incidence of HNSCC is growing with increasing consumption of tobacco (smoked or chewed), alcohol, and areca nut (betel quid). Alcohol and tobacco have a synergistic effect, with the heavy consumption of both increasing HNSCC risk 40-fold. In developed nations, HPV-related HNSCC surpasses tobacco- and alcohol-related disease. HPV-related HNSCC more commonly affects the oropharynx, hypopharynx, and larynx than the oral cavity, and is associated with a significantly longer median survival (130 months vs. 20 months). Discrepancies in etiology as well as disparities in lifestyle choices and access to healthcare may account for the greater incidence and poorer survival of HNSCC among minority and lower-socioeconomic-status communities in developed nations. Pharmacotherapy and counseling together have been shown to be effective in promoting smoking and alcohol cessation. Education on cancer risk and community engagement have reduced areca nut consumption in Asia as well as in diaspora communities. HPV vaccination, starting at age 11–12 for both sexes, has been shown to reduce the prevalence of high-risk HPV serologies and prevent pre-cancerous lesions of the cervix, vagina, and vulva. As of 2020, 58.6% of eligible adolescents in the US have received the full two-vaccine series. Increased adoption of vaccination, education on safe sex practices, and routine visual oral screening for high-risk patients would curb growing HNSCC incidence in developed nations. Full article

Hypoxia is characterized as one of the main consequences of sepsis, which is recognized as the leading cause of death in intensive care unit (ICU) patients. In this study, we aimed to examine whether the expression levels of genes regulated under hypoxia could be utilized as novel biomarkers for sepsis prognosis in ICU patients. Whole blood expression levels of hypoxia-inducible factor-1α (HIF1A), interferon-stimulated gene 15 (ISG15), hexokinase 2 (HK2), lactate dehydrogenase (LDHA), heme oxygenase-1 (HMOX1), erythropoietin (EPO), and the vascular endothelial growth factor A (VEGFA) were measured on ICU admission in 46 critically ill, initially non-septic patients. The patients were subsequently divided into two groups, based on the development of sepsis and septic shock (n = 25) or lack thereof (n = 21). HMOX1 mRNA expression was increased in patients who developed sepsis/septic shock compared to the non-septic group (p < 0.0001). The ROC curve, multivariate logistic regression, and Kaplan–Meier analysis demonstrated that HMOX1 expression could be utilized for sepsis and septic shock development probability. Overall, our results indicate that HMOX1 mRNA levels have the potential to be a valuable predictive factor for the prognosis of sepsis and septic shock in ICU patients. Full article

Background/Objectives: Comprehensive Geriatric Care (CGC) is a specific multimodal treatment for older patients. In the current study, we aimed to investigate walking performance after CGC in medically ill patients versus those with fractures. Methods: The timed up and go test (TuG), a 5-grade scale assessment (1 = no walking impairment to 5 = no walking ability at all) for evaluating individual walking ability was performed in all patients who underwent CGC prior to and after treatment. Factors associated with improvement in walking ability were analyzed in the subgroup of patients with fractures. Results: Out of 1263 hospitalized patients, 1099 underwent CGC (median age: 83.1 years (IQR 79.0–87.8 years); 64.1% were female). Patients with fractures (n = 300) were older than those without (n = 799), (median 85.6 versus 82.4 years, p = 0.001). Improvement in TuG after CGC was found in 54.2% of the fracture patients compared to just 45.9% of those without fractures. In fracture group patients, TuG improved from median 5 on admission to median 3 on discharge (p = 0.001). In fracture patients, improvement in walking ability was associated with higher Barthel index values on admission (median 45 (IQR: 35–55) versus 35 (IQR: 20–50): p = 0.001) and Tinetti assessment scores (median 9 (IQR: 4–14.25) versus 5 (IQR: 0–13); p = 0.001) and was negatively associated with the diagnosis of dementia (21.4% versus 31.5%; p = 0.058). Conclusion: CGC improved walking ability in more than half of all patients examined. Older patients in particular might benefit from undergoing the procedure after an acute fracture. A better initial functional status favors a positive result following the treatment. Full article

Background: Sleep is an essential element for patients’ recovery during a period of hospitalisation. Hospital Clínic de Barcelona has developed the ClíNit project to promote patients’ sleep by identifying elements that affect the quality of sleep and implementing actions to improve rest at night. Objective: Our aim is to select actions to improve sleep quality. Methods: The study population included night-shift nurses from two clinical units where the pilot actions were to be carried out (n: 14). The nurses prioritised actions to improve sleep quality using the methodology proposed by Fogg: clarification, magic wand, crispification, and the focus-mapping technique. Results: Two sessions were organised for each unit and 32 actions considered high impact and easy to implement were proposed, of which 43.75% (14/32) were directly dependent on nurses. It was then agreed to implement four of these pilot studies. Conclusions: One aspect worth highlighting is that using prioritization techniques such as the Fogg technique is a good strategy to implement the general objectives of intervention programmes in large organizations in an easy way. Full article

In heart failure (HF) with reduced ejection fraction (HFrEF), four classes of drugs (β-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor neprilysin inhibitors, mineralocorticoid receptor antagonists, and the most recent Sodium–Glucose Co-Transporters 2 Inhibitors) have demonstrated positive results in randomized controlled trials (RCTs). Nevertheless, the latest RCTs are not proper for comparison since they were carried out at various times with dissimilar background therapies and the patients enrolled did not have the same characteristics. The difficulty of extrapolating from these trials and proposing a common framework appropriate for all cases is thus obvious. Despite the fact that these four agents are now the fundamental pillars of HFrEF treatment, the built-up algorithm of initiation and titration is a matter of debate. Electrolyte disturbances are common in HFrEF patients and can be attributed to several factors, such as the use of diuretics, renal impairment, and neurohormonal activation. We have identified several HFrEF phenotypes according to their sodium (Na⁺) and potassium (K⁺) status in a “real world” setting and suggest an algorithm on how to introduce the most appropriate drug and set up therapy based on the patients’ electrolytes and the existence of congestion. Full article

There is widespread use of dietary supplements, some prescribed but many taken without a physician’s guidance. There are many potential interactions between supplements and both over-the-counter and prescription medications in ways that are unknown to patients. Structured medical records do not adequately document supplement use; however, unstructured clinical notes often contain extra information on supplements. We studied a group of 377 patients from three healthcare facilities and developed a natural language processing (NLP) tool to detect supplement use. Using surveys of these patients, we investigated the correlation between self-reported supplement use and NLP extractions from the clinical notes. Our model achieved an F1 score of 0.914 for detecting all supplements. Individual supplement detection had a variable correlation with survey responses, ranging from an F1 of 0.83 for calcium to an F1 of 0.39 for folic acid. Our study demonstrated good NLP performance while also finding that self-reported supplement use is not always consistent with the documented use in clinical records. Full article

Objectives: We sought to evaluate the effect of gender on biology, therapeutic decisions, and survival in patients with severe aortic regurgitation (AR). Background: Gender affects adaptive response to the presence of valvular heart diseases and therapeutic decisions. The impact of these on survival in severe AR patients is not known. Methods: This observational study was compiled from our echocardiographic database which was screened (1993–2007) for patients with severe AR. Detailed chart reviews were performed. Mortality data were obtained from the Social Security Death Index and analyzed as a function of gender. Results: Of the 756 patients with severe AR, 308 (41%) were women. Over a follow-up of up to 22 years, there were 434 deaths. Women compared to men were older (64 ± 18 vs. 59 ± 17 years, p = 0.0002). Women also had smaller left ventricular (LV) end diastolic dimension (5.2 ± 1.1 vs. 6.0 ± 1.0 cm, p < 0.0001), higher EF (56% ± 17% vs. 52% ± 18%, p = 0.003), higher prevalence of diabetes mellitus (18% vs. 11%, p = 0.006), and higher prevalence of ≥2+ mitral regurgitation (52% vs. 40%, p = 0.0008) despite a smaller LV size. Women were also less likely to receive aortic valve replacement (AVR) (24% vs. 48%, p < 0.0001) compared to men and had a lower survival on univariate analysis (p = 0.001). However, after adjusting for group differences including AVR rates, gender was not an independent predictor of survival. However, the survival benefit associated with AVR was similar in both women and men. Conclusions: This study strongly suggests that female gender is associated with different biological responses to AR compared to men. There is also a lower AVR rate in women, but women derive similar survival benefit as men with AVR. Gender does not seem to affect survival in an independent fashion in patients with severe AR after adjusting for group differences and AVR rates. Full article

Metaplastic carcinoma of the breast (MpBC) is a very rare and aggressive type of breast cancer. Data focusing on MpBC are limited. The aim of this study was to describe the clinicopathological features of MpBC and evaluate the prognosis of patients with MpBC. Eligible articles about MpBC were identified by searching CASES SERIES gov and the MEDLINE bibliographic database for the period of 1 January 2010 to 1 June 2021 with the keywords metaplastic breast cancer, mammary gland cancer, neoplasm, tumor, and metaplastic carcinoma. In this study, we also report 46 cases of MpBC stemming from our hospital. Survival rates, clinical behavior, and pathological characteristics were analyzed. Data from 205 patients were included for analysis. The mean age at diagnosis was 55 (14.7) years. The TNM stage at diagnosis was mostly stage II (58.5%) and most tumors were triple negative. The median overall survival was 66 (12–118) months, and the median disease-free survival was 56.8 (11–102) months. Multivariate Cox regression analysis revealed that surgical treatment was associated with decreased risk of death (hazard ratio 0.11, 95% confidence interval 0.02–0.54, p = 0.01) while advanced TNM stage was associated with increased risk of death (hazard ratio 1.5, 95% confidence interval 1.04–2.28, p = 0.03). Our results revealed that surgical treatment and TNM stage were the only independent risk factors related to patients’ overall survival. Full article

Cervical artery dissection (CAD) and Patent Foramen Ovale (PFO) are important causes of stroke in young patients. Although PFO is considered an independent risk factor for cerebral infarction in young adults with cryptogenic stroke, other concomitant causes may be necessary to cause brain injury. PFO could be a predisposing factor of stroke through several mechanisms including paradoxical embolism from a venous source, thrombus formation in atrial septum, or atrial arrhythmias causing cerebral thromboembolism. The pathophysiology of CAD is poorly understood and includes both constitutional and environmental factors. A causal association is often difficult to establish, as other predisposing factors may also play a role in CAD etiopathogenesis. We present a family with ischemic stroke (a father and his three daughters), in which the two different stroke causes are present. We hypothesized that a paradoxical embolism caused by PFO, associated with arterial wall disease, in the presence of a procoagulant state, could produce arterial dissection and then stroke. Full article

Previous studies have demonstrated gender disparities in mortality and vascular complications after transcatheter aortic valve replacement (TAVR) with early generation transcatheter heart valves (THVs). It is unclear, however, whether gender-related differences persist with the newer generation THVs. We aim to assess gender disparities after TAVR with newer generation THVs. The MEDLINE and Embase databases were thoroughly searched from inception to April 2023 to identify studies that reported gender-specific outcomes after TAVR with newer generation THVs (Sapien 3, Corevalve Evolut R, and Evolut Pro). The outcomes of interest included 30-day mortality, 1-year mortality, and vascular complications. In total, 5 studies (4 databases) with a total of 47,933 patients (21,073 females and 26,860 males) were included. Ninety-six percent received TAVR via the transfemoral approach. The females had higher 30-day mortality rates (odds ratio (OR) = 1.53, 95% confidence interval (CI) 1.31–1.79, p-value (p) < 0.001) and vascular complications (OR = 1.43, 95% CI 1.23–1.65, p < 0.001). However, one-year mortality was similar between the two groups (OR = 0.78, 95% CI 0.61–1.00, p = 0.28). The female gender continues to be associated with higher 30-day mortality rates and vascular complications after TAVR with newer generation transcatheter heart valves, while there was no difference in 1-year mortality between the genders. More data is needed to explore the causes and whether we can improve TAVR outcomes in females. Full article

Background: Primary malignant melanomas of the Gastrointestinal mucosa are uncommon. Most cases of gastrointestinal (GI) melanomas are secondary, arising from metastasis at distant sites. The purpose of this study is to assess to what extent the interaction between independent prognostic factors (age and tumor site) of primary GI melanoma influence survival. Furthermore, we also aimed to investigate the clinical characteristics, survival outcomes, and independent prognostic factors of patients with primary GI melanoma in the past decade. Methods: A total of 399 patients diagnosed with primary GI melanoma, between 2008 and 2017, were enrolled in our study by retrieving data from the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of primary GI melanoma. Variables with a p value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox model (model 1) to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors. Furthermore, we analyzed the effect of the interaction between age and primary location on mortality (model 2). Results: Multivariate cox proportional hazard regression analyses revealed higher OM in age group 80+ (HR = 5.653, 95% CI 2.212–14.445, p = 0), stomach location of the tumor (HR = 2.821, 95% CI 1.265–6.292, p = 0.011), regional lymph node involvement only (HR = 1.664, 95% CI 1.051–2.635, p < 0.05), regional involvement by both direct extension and lymph node involvement (HR = 1.755, 95% CI 1.047–2.943, p < 0.05) and distant metastases (HR = 4.491, 95% CI 3.115–6.476, p = 0), whereas the lowest OM was observed in patients with small intestine melanoma (HR = 0.383, 95% CI 0.173–0.846, p < 0.05). Multivariate cox proportional hazard regression analyses of CSM also revealed higher mortality of the same groups and lower CSM in small intestine and colon melanoma excluding the rectum. For model 2, considering the interaction between age and primary site on mortality, higher OM was found in age group 80+, followed by age group 40–59 then age group 60–79, regional lymph node involvement only, regional involvement by both direct extension and lymph node involvement and distant metastases. The small intestine had a lower OM. The rectum as primary location and the age range 40–59 interacted to lower the OM (HR = 0.14, 95% CI 0.02–0.89, p = 0.038). Age and primary gastric location did not interact to affect the OM. For the CSM, taking into account the interaction between age and the primary location, higher mortality was found in the same groups and the colon location. The primary colon location also interacted with the age group 40–59 to increase the CSM (HR = 1.38 × 10⁹, 95% CI 7.80 × 10⁷–2.45 × 10¹⁰, p = 0). Conclusions: In this United States population-based retrospective cohort study using the SEER database, we found that only the age range 40–59 interacted with the rectum and colon to lower and increase mortality respectively. Primary gastric location, which was the single most important location to affect mortality, did not interact with any age range to influence mortality. With those results, we hope to shed some light on this rare pathology with a very dismal prognosis. Full article

Chemokines are a group of cytokines involved in the mobilization of leukocytes, which play a role in host defense and a variety of pathological conditions, including cancer. Interferon (IFN)-inducible chemokines C-X-C motif ligand 9 (CXCL), CXCL10, and CXCL11 are anti-tumor chemokines; however, the differential anti-tumor effects of IFN-inducible chemokines are not completely understood. In this study, we investigated the anti-tumor effects of IFN-inducible chemokines by transferring chemokine expression vectors into a mouse squamous cell carcinoma cell line, SCCVII, to generate a cell line stably expressing chemokines and transplanted it into nude mice. The results showed that CXCL9- and CXCL11-expressing cells markedly inhibited tumor growth, whereas CXCL10-expressing cells did not inhibit growth. The NH₂-terminal amino acid sequence of mouse CXCL10 contains a cleavage sequence by dipeptidyl peptidase 4 (DPP4), an enzyme that cleaves the peptide chain of chemokines. IHC staining indicated DPP4 expression in the stromal tissue, suggesting CXCL10 inactivation. These results suggest that the anti-tumor effects of IFN-inducible chemokines are affected by the expression of chemokine-cleaving enzymes in tumor tissues. Full article

Background: Atrial fibrillation (AF) is the most common pathological arrhythmia, and its complications lead to significant morbidity and mortality. However, patients with AF can often go undetected, especially if they are asymptomatic or have a low burden of paroxysms. Identification of those at high risk of AF development may help refine screening and management strategies. Methods: PubMed and Embase databases were systematically searched for studies looking at electrocardiographic predictors of AF from inception to August 2021. Results: A total of 115 studies were reported which examined a combination of atrial and ventricular parameters that could be electrocardiographic predictors of AF. Atrial predictors include conduction parameters, such as the PR interval, p-wave index and dispersion, and partial interatrial or advanced interatrial block, or morphological parameters, such as p-wave axis, amplitude and terminal force. Ventricular predictors include abnormalities in QRS amplitude, morphology or duration, QT interval duration, r-wave progression and ST segment, i.e., t-wave abnormalities. Conclusions: There has been significant interest in electrocardiographic prediction of AF, especially in populations at high risk of atrial AF, such as those with an embolic stroke of undetermined source. This review highlights the breadth of possible predictive parameters, and possible pathological bases for the predictive role of each parameter are proposed. Full article

Recent identification of four additional polyaminopathies, including Bachmann–Bupp syndrome, have benefited from previous research on Snyder–Robinson syndrome in order to advance from research to treatment more quickly. As a result of the discovery of these conditions, the potential for treatment within this pathway, and for other possible unidentified polyaminopathies, the International Center for Polyamine Disorders (ICPD) was created to help promote understanding of these conditions, research opportunities, and appropriate care for families. This case study provides insights from two new patients diagnosed with Bachmann–Bupp syndrome, further expanding our understanding of this ultra-rare condition, as well as a general discussion about other known polyaminopathies. This work also presents considerations for collaborative research efforts across these conditions, along with others that are likely to be identified in time, and outlines the role that the ICPD hopes to fill as more patients with these polyaminopathies continue to be identified and diagnosed. Full article

Antimicrobial drug resistance in Neisseria gonorrhoeae has been documented all over the world. However, the situation in Sub-Saharan Africa has received little attention. It is critical to establish diagnostics and extend surveillance in order to prevent the emergence of illnesses that are resistant to several treatments. Monitoring antimicrobial susceptibility is critically required in order to gather data that may be utilised to produce treatment recommendations that will result in effective therapy, a decrease in gonorrhoeae-related difficulties and transmission, and effective therapy. Government authorities may set research and preventive objectives, as well as treatment recommendations, using data from the Gonococcal Antimicrobial Surveillance Program (GISP). Local and state health authorities may use GISP data to make choices about the allocation of STI prevention services and resources, to guide preventative planning, and to disseminate information about the most successful treatment practices. Using molecular and culture approaches, we investigated the occurrence of antibiotic resistance in isolates from KwaZulu Natal, South Africa. The great majority of gonococcal isolates (48% showed absolute resistance to ciprofloxacin), with penicillin and tetracycline resistance rates of 14% each. Only one of the gonococcal isolates tested positive for azithromycin resistance, with a minimum inhibitory concentration (MIC) of 1.5 µg/mL. Ceftriaxone was effective against all gonococcal isolates tested. Full article

Echocardiography is the gold standard clinical tool for the evaluation of left ventricular diastolic dysfunction (LVDD) and is used to validate other cardiac imaging modalities in measuring diastolic dysfunction. We examined Cardiac Magnetic Resonance Imaging (CMR) in detecting diastolic dysfunction using the time-volume curve-derived parameters compared to echocardiographic diastolic parameters. We evaluated patients who underwent both CMR and transthoracic echocardiography (TTE) within 2 ± 1 weeks of each other. On echo, Doppler/Tissue Doppler Imaging (TDI) measurements were obtained. On CMR, peak filling rate (PFR), time to PFR (TPFR), 1/3 filling fraction (1/3FF), and 1/3 filling rate (1/3FR) were calculated from the time-volume curve. Using the commonly employed E/A ratio, 44.4% of patients were found to have LVDD. Using septal E/E′ and lateral E/E′, 29.6% and 48.1% of patients had LVDD, respectively. Correlation was found between left atrial (LA) size and E/A ratio (R = −0.36). Using LVDD criteria for CMR, 63% of patients had diastolic dysfunction. CMR predicted LVDD in 66.7% of the cases. CMR-derived diastolic filling parameters provided a relatively easy and promising method for the assessment of LVDD and can predict the presence of LVDD as assessed by traditional Doppler and TDI methods. Full article

Background: Gastroduodenal perforation stands out as one of the complications in cancer patients. Despite its high mortality, its characteristics are still poorly described. This study aimed to evaluate the characteristics and outcomes of cancer patients who had gastroduodenal perforation, and the influence of chemotherapy (CMT) in these cases. Method: A retrospective analysis of patients who underwent emergency surgery with an intraoperative finding of gastroduodenal perforation. Patients who performed CMT within 60 days before perforation were considered as the CMT group. Results: Among 45 patients included, 16 (35.5%) were classified as the CMT group and the remaining 29 (64.5%) patients as the non-CMT group. There was no difference between the groups regarding sex, age, BMI, comorbidity, and laboratory exams. ECOG 2-3 was significantly more frequent in the CMT group (68.8% vs. 34.5% p = 0.027). Major postoperative complications were similar between both groups (75% vs. 58.6%, p = 0.272). The sepsis of abdominal focus was the main postoperative complication. The 30-day mortality was 55.6%, with no difference between non-CMT and CMT groups (62.5% vs. 51.7%, respectively; p = 0.486). A multivariate analysis of risk factors showed that only an age of ≥65 years was related to 30-day mortality. Conclusions: Patients with gastroduodenal perforation and oncologic treatment present high mortality, regardless of receiving recent CMT. Full article

The aim of the present study was to compare repaired Achilles tendon (AT) remodelling, whether its function was restored and what effects the surgery had on our patients’ gait cycle in a long-term follow-up study. The study population comprised 30 human subjects treated acutely and chronically for AT ruptures, using the same surgical technique in all cases. The study group was divided into two subgroups regarding the age of their AT injury, i.e., how much time elapsed between the injury and when a correct diagnosis was made and when adequate treatment was applied. Following these criteria, persons presenting at less than 4 weeks postinjury were classified as acute rupture (AR) patients and those presenting at more than 4 weeks after injury were grouped as chronic rupture (CR) patients. Both patient groups were operated on using a surgical method favoured at least a decade ago, i.e., open repair through a posteromedial approach. The AT was augmented with a plantaris longus tendon autograft, followed by suturing using the pull-out suture technique. The results were measured using clinical, ultrasonographic (US) and pedobarographic methods. Our ultrasonographic and pedobarographic findings revealed differences between both patient groups, thus indicating that delayed surgery had negative impacts on treatment success, however, with good long-term functional score outcomes in both patient groups. Nevertheless, delayed treatment of AT ruptures did not leave individual gait phases unaffected, as it also affected the plantar surface and balance performance of the affected limb. As per the results, the Achilles tendon manifested decreased capacity following delayed treatment; however, its long-term functional outcomes were favourable, irrespective of whether it was for acute or chronic patients. Full article