Morbidity Rates Research Articles

Use of Pharmacophore Modeling, 3D-atom-based QSAR, ADMET, Docking, and Molecular Dynamics Studies for the Development of Psoralen-based Derivatives as Antifungal Agents

Background:: The mortality and morbidity rates in patients caused by fungi are ex-tremely high. 3-4 % of species of fungi like Candida and Aspergillus are responsible for >99% of invasive fungal infections. Aim:: The goal of the current work was to use several In-silico methods, such as Pharmacophore modeling and 3D-QSAR, to design New chemical entities (NCEs) that have antifungal activity. Material & Method:: A dataset of 40 Psoralen derivatives was taken from available literature, and then, the pharmacophore hypothesis and 3D-QSAR model development were generated using Schrodinger 2023-1 software. After designing a library of 36 compounds, they were sub-jected to ADMET prediction. Screened compounds from the ADMET study were docked with 14 alpha demethylase CYP51 (PDB ID: 3LD6) using Schrödinger software. Molecular dynam-ics (MD) simulation studies were performed on PDB-3LD6 using Desmond-v7.2. Results & Discussion:: The top-ranked hypothesis, AHRRR_1, was taken into consideration when designing the library of potential NCEs.In order to check the drug likeliness of the com-pounds, all 36 designed NCEs were subjected to ADMET prediction using the QikProp tool. The majority of compounds have a good partition coefficient index (less than five). Qplog HERG value was found to be less, making them safer and less toxic. C- 4, 6, 9, 13, 15, 22, 24, 27, 31, and 33 have shown compliance with Lipinski’s rule with zero violations. Compounds C-9, C-13, C-22, C-24, and C-27 have shown better docking scores than the standard Ketocon-azole. Compounds C-9, 24, and 27 have shown a greater number of hydrophobic and hydrogen bond interactions in comparison with the other compounds. Compounds 9, 24, and 27 showed good stability after 100ns molecular simulation simulations. result: The top ranked hypothesis AHRRR_1 was taken into consideration when designing the library of potential NCE's.In order to check the drug likeliness of the compounds, all 36 designed NCE's were subjected to ADMET prediction using QikProp tool. The majority of compounds have good partition coefficient index (less than five), and Qplog HERG value was found to be less, making them safer and less toxic.C- 4, 6, 9, 13, 15, 22, 24, 27, 31, 33 have shown compliance to Lipinski’s rule with zero violations. The majority of the compounds had greater binding affinity than the standard Ketoconazole. Three compounds C-9, 24 and 27 have the good hydrophobic and hydrogen bonding interactions required for antifungal activity.The Compounds 9, 24 and 27 showed good stability after 100ns molecular simulation simulations. Conclusion:: In the current work, the application of insilico methods such as pharmacophore hypothesis, 3D QSAR, ADMET study, docking, and simulation studies have helped to optimize Psoralen pharmacophore for potential antifungal activity. Therefore, the outcomes of the present study could provide insights into the discovery of new potential alpha demethylase inhibitors with improved selectivity and activity against fungal infections. other: Nil

Morbi-mortality of surgical management in emergency of complicated diverticular sigmoiditis, retrospective monocentric study

IntroductionSigmoidal diverticulitis is the inflammation or infection of a diverticulum. It may be simple or complicate into an abscess, perforation, stenosis or fistula. These complications are referred to as diverticular disease. Surgical treatment may be required as an emergency measure in the event of serious signs, or at a later stage if disabling symptoms persist. The aim of this study was to assess the 90-day post-operative morbidity and mortality of complicated sigmoidal diverticulitis managed in emergency. MethodsWe retrospectively included all patients (n = 62) with complicated sigmoidal diverticulitis who underwent surgery between 2010 and 2019. 90-day mortality was assessed for each patient. Overall morbidity was assessed using the Dindo-Clavien classification, with major morbidity corresponding to stages ≥III. Factors predictive of overall and major morbidity were analyzed. ResultsPostoperative mortality at 90 days was nil. Overall morbidity at 90 days according to the Dindo-Clavien classification was 80,7 %, with major morbidity at 27,4 %. Multivariate logistic regression analysis retained male gender (OR=6.77[1,40; 32.74], p = 0.02), BMI over 25 (OR=58.82[3.95; 876.95], p = 0.01) and smoking (OR=8.77[0.84; 91.13], p = 0.07) as independent predictors of the occurrence of overall morbidity at 90 days. Likewise, only an ASA score ≥ III was highlighted as an independent predictive factor (OR=5.00[1.51; 16.51], p = 0.01) of major morbidity at 90 days (Dindo-Clavien ≥ III). ConclusionIn our study, mortality was nil, the overall morbidity rate was 80.7 % and 27.4 % for major morbidity. Nevertheless, the choice of surgical technique remains open to debate, given the absence of any difference in morbidity and mortality from anastomotic resection during emergency surgery, and the less morbid and easier restoration of digestive continuity afterwards in selected patients.

Advances in Mechanism of HIV-1 Immune Reconstitution Failure: Understanding Lymphocyte Subpopulations and Interventions for Immunological Nonresponders.

In individuals diagnosed with AIDS, the primary method of sustained suppression of HIV-1 replication is antiretroviral therapy, which systematically increases CD4+ T cell levels and restores immune function. However, there is still a subset of 10-40% of people living with HIV who not only fail to reach normal CD4+ T cell counts but also experience severe immune dysfunction. These individuals are referred to as immunological nonresponders (INRs). INRs have a higher susceptibility to opportunistic infections and non-AIDS-related illnesses, resulting in increased morbidity and mortality rates. Therefore, it is crucial to gain new insights into the primary mechanisms of immune reconstitution failure to enable early and effective treatment for individuals at risk. This review provides an overview of the dynamics of key lymphocyte subpopulations, the main molecular mechanisms of INRs, clinical diagnosis, and intervention strategies during immune reconstitution failure, primarily from a multiomics perspective.

Exploring 6years of colorectal cancer surgery in rural Italy: insights from 648 consecutive patients unveiling successes and challenges.

The multidisciplinary management of patients suffering from colorectal cancer (CRC) has significantly increased survival over the decades and surgery remains the only potentially curative option for it. However, despite the implementation of minimally invasive surgery and ERAS pathway, the overall morbidity and mortality remain quite high, especially in rural populations because of urban - rural disparities. The aim of the study is to analyze the characteristics and the surgical outcomes of a series of unselected CRC patients residing in two similar rural areas in Italy. A total of 648 consecutive patients of a median age of 73years (IQR 64-81) was enrolled between 2017 and 2022 in a prospective database. Emergency admission (EA) was recorded in 221 patients (34.1%), and emergency surgery (ES) was required in 11.4% of the patients. Tumor resection and laparoscopic resection rates were 95.0% and 63.2%, respectively. The median length of stay was 8days. The overall morbidity and mortality rates were 23.5% and 3.2%, respectively. EA was associated with increased median age (77.5 vs. 71 ys, p < 0.001), increased mean ASA Score (2.84 vs. 2.59; p = 0.002) and increased IV stage disease rate (25.3% vs. 11.5%, p < 0.001). EA was also associated with lower tumor resection rate (87.3% vs. 99.1%, p < 0.001), restorative resection rate (71.5 vs. 89.7%, p < 0.001), and laparoscopic resection rate (36.2 vs. 72.6%, p < 0.001). Increased mortality rates were associated with EA (7.2% vs. 1.2%, p < 0.001), ES (11.1% vs. 2.0%, p < 0.001) and age more than 80years (5.8% vs. 1.9%, p < 0.001). In rural areas, high quality oncologic care can be delivered in CRC patients. However, the surgical outcomes are adversely affected by a still too high proportion of emergency presentation of elderly and frail patients that need additional intensive care supports beyond the surgical skill and alternative strategies for earlier detection of the disease.

Strengthening neurosurgical training programs in Sub-saharan Africa: a medical student's perspective.

This article provides a nuanced exploration of the state and exigencies of neurosurgical training in sub-Saharan Africa (SSA), viewed through the discerning lens of a medical student. The region has a pronounced scarcity of neurosurgical services, further compounded by sociocultural intricacies and infrastructural inadequacies, resulting in elevated mortality and morbidity rates. The insufficiency of neurosurgeons, facilities, and training centers, particularly in remote areas, exacerbates this predicament. The imperative to fortify neurosurgical training programs is underscored, necessitating a multifaceted approach inclusive of international collaborations and innovative strategies. The challenges impeding neurosurgical training program implementation range from constrained infrastructure to faculty shortages and financial constraints. Recommendations encompass infrastructural investments, faculty development initiatives, and augmented community engagement. An exploration of neurosurgical training programs across diverse African regions reveals commendable strides and imminent deficits, warranting heightened international collaboration. Furthermore, technological innovations, including virtual reality, robotics, and artificial intelligence, are posited as transformative conduits for augmenting neurosurgical training in SSA. The article concludes with a sagacious compendium of recommendations, encompassing standardized curricula, mentorship paradigms, and stringent evaluation mechanisms, all combining efficaciously fortifying neurosurgical insight in SSA and producing transformative improvements in healthcare outcomes.

Meningites infecciosas: aspectos epidemiológicos da doença no estado de Mato Grosso do Sul

Introduction: Meningitis is a global medical emergency that requires immediate diagnosis and treatment due to its high mortality and morbidity rates. Objective: To depict the epidemiology of infectious meningitis in the state of Mato Grosso do Sul from 2010 to 2022. Method: For this research, a cross-sectional, descriptive, retrospective, and quantitative study was conducted using the state of Mato Grosso do Sul as the unit of analysis. The sample was delimited to the period from 2010 to 2022, and the information was coded and collected from the Notifiable Diseases Information System (SINAN), considering the year and month of notification, notification municipality, age, sex, race/color, education, etiology, serogroup, confirmation criteria, and case evolution. Results: During the analyzed period, 2,826 cases of meningitis were reported, with 71.3% confirmed. The most affected individuals were males of mixed race/color and children aged 0 to 9 years. The prevalence in the state was 7.7 cases per 10,000 inhabitants. The majority of meningitis cases (39.7%) were classified as unspecified meningitis and 23.1% as aseptic meningitis. The lethality rate during the study period was 11.3%, with a concentration of deaths at the extremes of age. Conclusions: Although meningitis is a well-known disease, its lethality rate remains high. It is suggested to intensify control and prevention actions in municipalities, combined with demonstrating the importance of notifying the disease to epidemiological surveillance, which will help in organizing more targeted and specific action strategies to combat cases.

Identification and validation of a prognostic signature based on six immune-related genes for colorectal cancer

BackgroundColorectal cancer (CRC) is a prevalent malignancy with high mortality and morbidity rates. Although the significant efficacy of immunotherapy is well established, it is only beneficial for a limited number of individuals with CRC.MethodsDifferentially expressed immune-related genes (DE-IRGs) were retrieved from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and ImmPort databases. A prognostic signature comprising DE-IRGs was developed using univariate, LASSO, and multivariate Cox regression analyses. A nomogram integrating the independent prognostic factors was also developed. CIBERSORT was used to assess immune cell infiltration (ICI). Furthermore, wound-healing, colony formation, migration, and invasion assays were performed to study the involvement of ACTG1 in CRC.ResultsA signature including six DE-IRGs was developed. The overall survival (OS) rate was accurately estimated for TCGA and GSE38832 cohorts. The risk score (RS) of the signature was an independent factor for OS. Moreover, a nomogram encompassing age, RS, and pathological T stage accurately predicted the long-term OS probability of individuals with CRC. The high-risk group had an elevated proportion of patients treated with ICIs, including native B cells, relative to the low-risk group. Additionally, ACTG1 expression was upregulated, which supported the proliferation, migration, and invasion abilities of CRC cells.ConclusionsAn immune-related prognostic signature was developed for predicting OS and for determining the immune status of individuals with CRC. The present study provides new insights into accurate immunotherapy for individuals with CRC. Moreover, ACTG1 may serve as a new immune biomarker.

Developing a Novel Murine Meningococcal Meningitis Model Using a Capsule-Null Bacterial Strain

Background: Neisseria meningitidis (meningococcus) is a Gram-negative bacterium that colonises the nasopharynx of about 10% of the healthy human population. Under certain conditions, it spreads into the body, causing infections with high morbidity and mortality rates. Although the capsule is the key virulence factor, unencapsulated strains have proved to possess significant clinical implications as well. Meningococcal meningitis is a primarily human infection, with limited animal models that are dependent on a variety of parameters such as bacterial virulence and mouse strain. In this study, we aimed to develop a murine Neisseria meningitidis meningitis model to be used in the study of various antimicrobial compounds. Method: We used a capsule-deficient Neisseria meningitidis strain that was thoroughly analysed through various methods. The bacterial strain was incubated for 48 h in brain–heart infusion (BHI) broth before being concentrated and injected intracisternally to bypass the blood–brain barrier in CD-1 mice. This prolonged incubation time was a key factor in increasing the virulence of the bacterial strain. A total of three more differently prepared inoculums were tested to further solidify the importance of the protocol (a 24-h incubated inoculum, a diluted inoculum, and an inactivated inoculum). Antibiotic treatment groups were also established. The clinical parameters and number of deaths were recorded over a period of 5 days, and comatose mice with no chance of recovery were euthanised. Results: The bacterial strain was confirmed to have no capsule but was found to harbour a total of 56 genes coding virulence factors, and its antibiotic susceptibility was established. Meningitis was confirmed through positive tissue culture and histological evaluation, where specific lesions were observed, such as perivascular sheaths with inflammatory infiltrate. In the treatment groups, survival rates were significantly higher (up to 81.25% in one of the treatment groups compared to 18.75% in the control group). Conclusion: We managed to successfully develop a cost-efficient murine (using simple CD-1 mice instead of expensive transgenic mice) meningococcal meningitis model using an unencapsulated strain with a novel method of preparation.

Analysis of Treatment Strategies and Outcomes in Malignant Peritoneal Mesothelioma: Insights From a Multi-Center Study.

This study aimed to evaluate the demographic," clinicopathologic, and prognostic characteristics of malignant peritoneal mesothelioma (MPeM), as well as the treatment options for the rare and heterogeneous MPeM population. A retrospective multi-center observational cohort study was conducted to evaluate patients with MPeM. Due to the heterogeneity of the study population, the study divided them into two main groups in terms of treatments, follow-up periods, and prognostic features. The first group comprised the patients who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and the second group included the patients with metastatic disease for whom curative intent surgery was not possible. The patients' diagnostic procedures and treatments were identified from medical records. Patients older than 18 years old were included in the study regardless of asbestos exposure. Well-differentiated papillary and multicystic mesothelioma histologic types were not included in the study. The study evaluated 118 patients from five centers. Survival times, prognosis, and treatment responses were analyzed in both groups. The study showed that CRS-HIPEC was associated with longer overall survival (OS) and progression-free survival (PFS). Perioperative therapy was evaluated in subgroup analyses of this population and shown to provide survival benefits. The patients treated with chemotherapy (metastatic and medically inoperable patients and those for whom complete cytoreduction was not achievable) had a poorer prognosis than the surgery group. The study showed that life expectancy decreased significantly for the patients not suitable to undergo surgery for any reason. According to data from experienced centers, CRS-HIPEC is a treatment option recognized as effective, cost-effective, and safe, with better OS and PFS , as well as low morbidity and mortality rates similar to those in the literature. In addition, the platinum-pemetrexed combination continues to be an effective and acceptable treatment option for metastatic patients, those who are medically inoperable, and those for whom complete or near-complete cytoreduction is not achievable.

Early-pregnancy N-terminal pro-brain natriuretic peptide level is inversely associated with hypertensive disorders of pregnancy diagnosed after 35 weeks of gestation

Hypertensive disorders of pregnancy (HDP) are among the major causes of high maternal and fetal/neonatal morbidity and mortality rates. Patients with HDP have significantly elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at diagnosis; however, the NT-proBNP levels during early pregnancy are largely unknown. This study aimed to validate the association between HDP and NT-proBNP levels. This retrospective study evaluated 103 pregnant women who developed HDP diagnosed after 35 weeks of gestation and 667 who did not. The HDP group had significantly lower early-pregnancy NT-proBNP levels than the without HDP group. However, the two groups did not significantly differ in terms of the late-pregnancy NT-proBNP levels. After adjusting for confounding factors such as age, body mass index, parity, and blood pressure levels, high early-pregnancy NT-proBNP levels were associated with a lower HDP risk. Early-pregnancy NT-proBNP levels ≥ 60.5 pg/mL had a negative predictive value of 97.0% for ruling out HDP, with a sensitivity of 87.4% and specificity of 62.5%. In conclusion, elevated early-pregnancy NT-proBNP levels were associated with a lower HDP risk. Moreover, a cutoff point of ≥ 60.5 pg/mL for early-pregnancy NT-proBNP levels had a high negative predictive value and sensitivity for ruling out HDP. These findings can provide new clinical implications.

Exploring the pathways of drug repurposing and Panax ginseng treatment mechanisms in chronic heart failure: a disease module analysis perspective.

Chronic Heart Failure (CHF) is a significant global public health issue, with high mortality and morbidity rates and associated costs. Disease modules, which are collections of disease-related genes, offer an effective approach to understanding diseases from a biological network perspective. We employed the multi-Steiner tree algorithm within the NeDRex platform to extract CHF disease modules, and subsequently utilized the Trustrank algorithm to rank potential drugs for repurposing. The constructed disease module was then used to investigate the mechanism by which Panax ginseng ameliorates CHF. The active constituents of Panax ginseng were identified through a comprehensive review of the TCMSP database and relevant literature. The Swiss target prediction database was utilized to determine the action targets of these components. These targets were then cross-referenced with the CHF disease module in the STRING database to establish protein-protein interaction (PPI) relationships. Potential action pathways were uncovered through Gene Ontology (GO) and KEGG pathway enrichment analyses on the DAVID platform. Molecular docking, the determination of the interaction of biological macromolecules with their ligands, and visualization were conducted using Autodock Vina, PLIP, and PyMOL, respectively. The findings suggest that drugs such as dasatinib and mitoxantrone, which have low docking scores with key disease proteins and are reported in the literature as effective against CHF, could be promising. Key components of Panax ginseng, including ginsenoside rh4 and ginsenoside rg5, may exert their effects by targeting key proteins such as AKT1, TNF, NFKB1, among others, thereby influencing the PI3K-Akt and calcium signaling pathways. In conclusion, drugs like dasatinib and midostaurin may be suitable for CHF treatment, and Panax ginseng could potentially mitigate the progression of CHF through a multi-component-multi-target-multi-pathway approach. Disease module analysis emerges as an effective strategy for exploring drug repurposing and the mechanisms of traditional Chinese medicine in disease treatment.

Generation of Alzheimer’s Disease Model Derived from Induced Pluripotent Stem Cells with APP Gene Mutation

Alzheimer’s disease (AD), the most common cause of dementia, is characterized by disruptions in memory, cognition, and personality, significantly impacting morbidity and mortality rates among older adults. However, the exact pathophysiological mechanism of AD remains unknown, and effective treatment options for AD are still lacking. Human induced pluripotent stem cells (iPSC) are emerging as promising platforms for disease research, offering the ability to model the genetic mutations associated with various conditions. Patient-derived iPSCs are useful for modeling neurodegenerative and neurodevelopmental disorders. In this study, we generated AD iPSCs from peripheral blood mononuclear cells obtained from a 65-year-old patient with AD carrying the E682K mutation in the gene encoding the amyloid precursor protein. Cerebral organoids derived from AD iPSCs recapitulated the AD phenotype, exhibiting significantly increased levels of tau protein. Our analysis revealed that an iPSC disease model of AD is a valuable assessment tool for pathophysiological research and drug screening.

Malignant tumor increases the risk of all causes in-hospital mortality in critically ill patients with ischemic stroke: analysis of the MIMIC-IV database.

Ischemic stroke (IS) and malignant tumor (MT) have high morbidity and mortality rates worldwide, and several associations exist between them. This study aimed to determine the effect of MT on hospital mortality in patients with IS. Based on their MT status, participants with IS in the Medical Information Mart for Intensive Care IV (MIMIC-IV) were divided into two groups. The primary outcome was in-hospital all causes mortality. Kaplan-Meier survival analysis was performed to evaluate the intergroup in-hospital mortality, and three Cox regression models were used to determine the association between MT and in-hospital mortality. A total of 1605 participants (749 males and 856 females) were included in the study. The mean age was 72.030 ± 15.463 years. Of these, 257 (16%) patients died in the hospital. Kaplan-Meier analysis showed that the MT group had a significantly lower possibility of in-hospital survival than the non-MT group. In the unadjusted model, in-hospital mortality among MT patients had a higher odds ratio (OR) of 1.905 (95% CI, 1.320-2.748; P < 0.001) than the non-MT group. After adjusting for basic information, vital signs, and laboratory data, MT was also associated with increased in-hospital mortality (OR = 1.844, 95% CI: 1.255-2.708; P = 0.002). Among the patients with IS, the risk of all causes in-hospital mortality was higher for MT than for patients non-MT. This finding can assist clinicians in more accurately assessing prognosis and making informed treatment decisions.

INGUINAL HERNIA REPAIR: TRANSABDOMINAL PREPERITONEAL (TAPP) VERSUS LICHTENSTEIN HERNIOPLASTY

Abstract Background Inguinal hernias are one of the most common surgical pathologies in digestive surgery. The classical Lichtenstein repair (LR), long-considered as the gold standard, has been challenged since the 1990s by a minimally-invasive laparoscopic technique (TAPP). The aim of this study was to compare the short- and medium-term postoperative outcomes between LR and TAPP. Methods We conducted a cross-sectional study including tunisian patients followed up for inguinal hernia repair in the digestive surgery department, over a period of a year. The study population was prospectively randomized between January 2020 and December 2020 to receive either LR or TAPP. The main outcome measure was hernia recurrence. Chronic postoperative pain and quality of life were the secondary outcome measures. Results Twenty-five patients underwent TAPP repair and 31 underwent LR. The average age of patients was 53.2 years. In the TAPP group, the operative time was significantly longer (p = 0.002) and the recovery was faster (p = 0.005). The LR group had higher visual analogue scale scores in the early postoperative (p &amp;lt;0.001), higher morbidity rate (p = 0.003) and complications such as hematomas (p = 0.022) and seromas (p = 0.043). Chronic postoperative pain was more prevalent in the LR Group than the TAPP group (p = 0.022). Both the LR and TAPP had no recurrences of hernia. Conclusion The TAPP procedure, despite the longer operative time, provided patients with postoperative comfort, fast recovery, less complications and reduced postoperative pain.

OPTIMIZING THERAPEUTIC APPROACH FOR EFFECTIVE MANAGEMENT OF EMERGENCY STRANGULATED INGUINAL HERNIA

Abstract Background Inguinal hernias are a frequent reason for emergency settings. Incarcerated cases carry significant risk of strangulation. The approach to emergency treatment depends on the patient’s and environment conditions. However, the utilization of prosthetics in strangulated hernia treatment is constrained by concerns surrounding complications in a septic environment and the urgent situation. A prospective observational study was followed. Objective The aim of this study is to determine whether the utilisation of prothesis in managing strangulated hernias correlates with an elevated incidence of post operative events. Methods A total of 223 patients with a strangulated inguinal hernia who underwent surgical intervention. Inclusion criteria encompassed patients aged 15 years and above, admitted on an emergency basis with a strangulated hernia, and categorized as Asa III or lower. Results All admitted patients presented with a strangulated inguinal hernia. The average age was 55 years. Occlusive syndrome occurred in 17% of cases. The contents of the hernia sac varied, with 70% being non suffering, 19% containing epiploic content, 6% colonic, and 5% requiring anastomosis resection due to intestinal suffering. Among 223 patients who underwent hernioplasty using the Lichtenstein procedure, the mortality rate was 0.9%, and the morbidity rate reached 17%. parietal sepsis accounted for 6.72 %, serum related issue for 5.82%, and hematomas for 4.48%, with no reported instances of prosthesis removed. Conclusion In light of the result of this study, the consideration to utilize a prosthesis in emergency hernia situations warrants careful evaluation, taking into account therapeutic criteria and prevailing conditions.

There is high variability in quantitative measurement techniques in glenohumeral capsular measurements for shoulder instability: A systematic review.

Instability of the glenohumeral joint remains a complex clinical issue with high rates of surgical failure and significant morbidity. Advances in specific radiologic measurements involving the glenoid and the humerus have provided insight into glenohumeral pathology, which can be corrected surgically towards improving patient outcomes. The contributions of capsular pathology to ongoing instability remain unclear. The purpose of this study is to provide a systematic review of existing glenohumeral capsular measurement techniques published in the last 15 years. A systematic review of multiple databases was performed following PRISMA guidelines for all primary research articles between 2008 and 2023 with quantitative measurements of the glenohumeral capsule in patients with instability, including anterior, posterior and multi-directional instability. There were a total of 14 articles meeting the inclusion criteria. High variability in measurement methodology across studies was observed, including variable amounts of intra-articular contrast, heterogeneity among magnetic resonance sequence acquisitions, differences in measurements performed and the specific approach taken to compute each measurement. There is a need for standardization of methods in the measurement of glenohumeral capsular pathology in the setting of glenohumeral instability to allow for cross-study analysis. Level III.

Therapeutic potential of urine-derived stem cells in renal regeneration following acute kidney injury: A comparative analysis with mesenchymal stem cells

BACKGROUND Acute kidney injury (AKI) is a common clinical syndrome with high morbidity and mortality rates. The use of pluripotent stem cells holds great promise for the treatment of AKI. Urine-derived stem cells (USCs) are a novel and versatile cell source in cell-based therapy and regenerative medicine that provide advantages of a noninvasive, simple, and low-cost approach and are induced with high multidifferentiation potential. Whether these cells could serve as a potential stem cell source for the treatment of AKI has not been determined. AIM To investigate whether USCs can serve as a potential stem cell source to improve renal function and histological structure after experimental AKI. METHODS Stem cell markers with multidifferentiation potential were isolated from human amniotic fluid. AKI severe combined immune deficiency (SCID) mice models were induced by means of an intramuscular injection with glycerol. USCs isolated from human-voided urine were administered via tail veins. The functional changes in the kidney were assessed by the levels of blood urea nitrogen and serum creatinine. The histologic changes were evaluated by hematoxylin and eosin staining and transferase dUTP nick-end labeling staining. Meanwhile, we compared the regenerative potential of USCs with bone marrow-derived mesenchymal stem cells (MSCs). RESULTS Treatment with USCs significantly alleviated histological destruction and functional decline. The renal function was rapidly restored after intravenous injection of 5 × 105 human USCs into SCID mice with glycerol-induced AKI compared with injection of saline. Results from secretion assays conducted in vitro demonstrated that both stem cell varieties released a wide array of cytokines and growth factors. This suggests that a mixture of various mediators closely interacts with their biochemical functions. Two types of stem cells showed enhanced tubular cell proliferation and decreased tubular cell apoptosis, although USC treatment was not more effective than MSC treatment. We found that USC therapy significantly improved renal function and histological damage, inhibited inflammation and apoptosis processes in the kidney, and promoted tubular epithelial proliferation. CONCLUSION Our study demonstrated the potential of USCs for the treatment of AKI, representing a new clinical therapeutic strategy.

α5-nAChR/ADAM10 signaling mediates nicotine-related cutaneous melanoma progression via STAT3 activation.

Skin cutaneous melanoma (SKCM) is the skin malignancy with the highest mortality rate, and its morbidity rate is on the rise worldwide. Smoking is an independent marker of poor prognosis in melanoma. The α5-nicotinic acetylcholine receptor (α5-nAChR), one of the receptors for nicotine, is involved in the proliferation, migration and invasion of SKCM cells. Nicotine has been reported to promote the expression of a disintegrin and metalloproteinase 10 (ADAM10), which is the key gene involved in melanoma progression. Here, we explored the link between α5-nAChR and ADAM10 in nicotine-associated cutaneous melanoma. α5-nAChR expression was correlated with ADAM10 expression and lower survival in SKCM. α5-nAChR mediated nicotine-induced ADAM10 expression via STAT3. The α5-nAChR/ADAM10 signaling axis was involved in the stemness and migration of SKCM cells. Furthermore, α5-nAChR expression was associated with ADAM10 expression, EMT marker expression and stemness marker expression in nicotine-related mice homograft tissues. These results suggest the role of the α5-nAChR/ADAM10 signaling pathway in nicotine-induced melanoma progression.

Insight on Pediatric Burn Morbidity and Mortality at a Tertiary Indian Burn Care Center: A Case For Burn Prevention.

Pediatric burns pose a significant health burden in LMICs. Despite efforts to address burn prevention and management, morbidity and mortality rates remain high, particularly among children. Understanding pediatric burn epidemiology and predictors of clinical outcomes is crucial for developing effective prevention strategies and improving patient-care. This retrospective cohort study analyzed pediatric burn patients admitted to a tertiary burn-center in India, between March-2022 and December-2023. Demographic date, burn characteristics, treatments, complications and outcomes were collected. Statistical analysis, including logistic and linear regression, was conducted to identify predictors of mortality, sepsis, and hospital stay length. Among 332 pediatric burn patients, median age was 3 years, with a male predominance. Scald burns were the most common, followed by electrical and flame burns. Median total body surface area burned was 20%, with upper and lower extremities most affected. The incidence of electrical burns increased with age and was associated with a longer length of stay. Mortality rate was 14.2%, with age >10 years, male gender, and TBSA >30% predicting mortality. Complications like sepsis significantly increased mortality risk, while deep burns were associated with longer hospital stays. This study underscores importance of targeted prevention efforts and specialized care. Scald burns among young children highlight the need for safer cooking practices, while the high incidence of electrical burns in older children suggests age-specific education interventions are necessary. Predictors of mortality identified can guide risk assessment and resource allocation, emphasizing the importance of infection control and wound management strategies in improving outcomes.

Real-world evaluation of nivolumab in patients with non-nasopharyngeal recurrent or metastatic head and neck cancer: a retrospective multi-center study by the Turkish Oncology Group (TOG).

Head and neck cancers (HNCs) represent a significant global health concern due to high morbidity and mortality rates. Despite therapeutic advances, the prognosis for advanced or recurrent cases remains challenging. Nivolumab obtained approval for recurrent or metastatic HNC based on the Phase III CheckMate 141 trial. This study aimed to evaluate the real-world outcomes of nivolumab in patients with non-nasopharyngeal HNC. In this multicenter retrospective study, we analyzed 124 patients with recurrent or metastatic non-nasopharyngeal HNC who received nivolumab in the second-line setting and beyond. Data were collected from 20 different cancer centers across Turkey. The effectiveness and safety of the treatment and survival outcomes were evaluated. Nivolumab exhibited favorable clinical responses, yielding an objective response rate of 29.9% and a disease control rate of 55.7%. Safety assessments revealed a generally well-tolerated profile, with no instances of treatment discontinuation or mortality due to side effects. Survival analysis disclosed a median overall survival (OS) of 11.8 (95% CI 8.4-15.2) months. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 1.64, p = 0.045), laryngeal location (HR: 0.531, p = 0.024), and neutrophil-to-lymphocyte ratio > 3.5 (HR: 1.97, p = 0.007) were independent predictors of OS. Nivolumab is an effective and safe treatment option for patients with recurrent or metastatic non-nasopharyngeal HNC in real-world settings. Further studies are needed on factors affecting response to treatment and survival outcomes.