How well does the virtual format of oncology multidisciplinary team meetings work? An assessment of participants' perspectives and limitations: A scoping review.

BACKGROUND: Virtual multidisciplinary team meetings (VMDTM) provide a standard of care that is not limited by physical distance or social restrictions. And so, when the COVID-19 pandemic imposed irrefutable social restrictions and made in-person meetings impossible, many hospitals switched to the VMDTMs. Although the pandemic might have highlighted the ease of VMDTMs, these virtual meetings have existed over the past decade, albeit less in importance. Despite their recent importance, no review has previously assessed the feasibility of VMDTMs through the eyes of the participants, the barriers participants face, nor their comparison with the in-person format. We undertook this scoping review to map existing literature and assess the perspectives of VMDTM participants. MATERIAL AND METHODS: We searched MEDLINE, Embase, CINAHL, and Google Scholar from inception till July 1st, 2023 to select studies that evaluated the perspectives of participants of VMDTMs regarding the core components that make up a VMDMT. Four authors, independently, extracted data from all included studies. Two authors separated data into major themes and sub-themes. RESULTS: We identified six core, intrinsic aspects of a VMDTM that are essential to its structure: (1) organization, (2) case discussion and decision-making, (3) teamwork and communication, (4) training and education, (5) technology, and (6) patient-related aspect. VMDTMs have a high overall satisfaction rating amongst participants. The preference, however, is for a hybrid model of multidisciplinary teams. VMDTMs offer support to isolated physicians, help address complex cases, and offer information that may not be available elsewhere. The periodical nature of VMDTMs is appropriate for their consideration as CMEs. Adequate technology is paramount to the sustenance of the format. CONCLUSION: VMDTMs are efficient and offer a multidisciplinary consensus without geographical limitations. Despite certain technical and social limitations, VMDTM participants are highly satisfied with the format, although the preference lies with a hybrid model.

Understanding the impact of structural modifications at the NNAT gene's post-translational acetylation site: in silico approach for predicting its drug-interaction role in anorexia nervosa.

PURPOSE: Anorexia nervosa (AN) is a neuropsychological public health concern with a socially disabling routine and affects a person's healthy relationship with food. The role of the NNAT (Neuronatin) gene in AN is well established. The impact of mutation at the protein's post-translational modification (PTM) site has been exclusively associated with the worsening of the protein's biochemical dynamics. METHODS: To understand the relationship between genotype and phenotype, it is essential to investigate the appropriate molecular stability of protein required for proper biological functioning. In this regard, we investigated the PTM-acetylation site of the NNAT gene in terms of 19 other specific amino acid probabilities in place of wild type (WT) through various in silico algorithms. Based on the highest pathogenic impact computed through the consensus classifier tool, we generated 3 residue-specific (K59D, P, W) structurally modified 3D models of NNAT. These models were further tested through the AutoDock Vina tool to compute the molecular drug binding affinities and inhibition constant (Ki) of structural variants and WT 3D models. RESULTS: With trained in silico machine learning algorithms and consensus classifier; the three structural modifications (K59D, P, W), which were also the most deleterious substitution at the acetylation site of the NNAT gene, showed the highest structural destabilization and decreased molecular flexibility. The validation and quality assessment of the 3D model of these structural modifications and WT were performed. They were further docked with drugs used to manage AN, it was found that the ΔGbind (kcal/mol) values and the inhibition constants (Ki) were relatively lower in structurally modified models as compared to WT. CONCLUSION: We concluded that any future structural variation(s) at the PTM-acetylation site of the NNAT gene due to possible mutational consequences, will serve as a basis to explore its relationship with the propensity of developing AN. LEVEL OF EVIDENCE: No level of evidence-open access bioinformatics research.

Comprehensive overview of human monkeypox: epidemiology, clinical features, pathogenesis, diagnosis and prevention.

Monkeypox (MPX) is a zoonotic disease caused by the monkeypox virus (MPXV), belonging to the orthopoxvirus genus with a presentation resembling smallpox making it historically challenging to distinguish the disease from smallpox clinically. Since a British citizen brought MPX into the country on 6 May 2022, there have been concerns about the re-emergence of the human MPXV. Since then, the WHO has reported 92 confirmed cases and 28 suspected cases in 13 nations where MPXV was not endemic. WHO declared MPX a 'public health emergency of international concern' on 23 July 2022. MPXV can spread either through human-human contact or animal-human contact. Respiratory droplets, direct contact with bodily fluids, contaminated patient surroundings or objects, and skin sores from an infected person have all been linked to the disease's transmission from one person to another. Fever, headache, lethargy, asthenia, enlargement of the lymph nodes, weariness, back pain, and myalgia are some of the symptoms that last from 2 to 5 weeks. It can be diagnosed using a range of diagnostic methods, including electron microscopy, Immunoglobulin M, enzyme-linked immunosorbent assay, polymerase chain reactions, histological analysis, immunofluorescent antibody testing, virus isolation, etc. Smallpox immunization before infection may lessen clinical symptoms and is around 85% effective in protecting from the MPXV.

Association of d-dimer levels with in-hospital outcomes among COVID-19 positive patients: a developing country multicenter retrospective cohort.

D-dimer levels, which originate from the lysis of cross-linked fibrin, are serially measured during coronavirus disease 2019 illness to rule out hypercoagulability as well as a septic marker. Methods: This multicenter retrospective study was carried out in two tertiary care hospitals in Karachi, Pakistan. The study included adult patients admitted with a laboratory-confirmed coronavirus disease 2019 infection, with at least one measured d-dimer within 24 h following admission. Discharged patients were compared with the mortality group for survival analysis. Results: The study population of 813 patients had 68.5% males, with a median age of 57.0 years and 14.0 days of illness. The largest d-dimer elevation was between 0.51-2.00 mcg/ml (tertile 2) observed in 332 patients (40.8%), followed by 236 patients (29.2%) having values greater than 5.00 mcg/ml (tertile 4). Within 45 days of hospital stay, 230 patients (28.3%) died, with the majority in the ICU (53.9%). On multivariable logistic regression between d-dimer and mortality, the unadjusted (Model 1) had a higher d-dimer category (tertile 3 and tertile 4) associated with a higher risk of death (OR: 2.15; 95% CI: 1.02-4.54, P=0.044) and (OR: 4.74; 95% CI: 2.38-9.46, P<0.001). Adjustment for age, sex, and BMI (Model 2) yields only tertile 4 being significant (OR: 4.27; 95% CI: 2.06-8.86, P<0.001). Conclusion: Higher d-dimer levels were independently associated with a high risk of mortality. The added value of d-dimer in risk stratifying patients for mortality was not affected by invasive ventilation, ICU stays, length of hospital stays, or comorbidities.

Adverse events following COVID-19 mRNA vaccines: A systematic review of cardiovascular complication, thrombosis, and thrombocytopenia.

BACKGROUND AND OBJECTIVES: Since publishing successful clinical trial results of mRNA coronavirus disease 2019 (COVID-19) vaccines in December 2020, multiple reports have arisen about cardiovascular complications following the mRNA vaccination. This study provides an in-depth account of various cardiovascular adverse events reported after the mRNA vaccines' first or second dose including pericarditis/myopericarditis, myocarditis, hypotension, hypertension, arrhythmia, cardiogenic shock, stroke, myocardial infarction/STEMI, intracranial hemorrhage, thrombosis (deep vein thrombosis, cerebral venous thrombosis, arterial or venous thrombotic events, portal vein thrombosis, coronary thrombosis, microvascular small bowel thrombosis), and pulmonary embolism. METHODS: A systematic review of original studies reporting confirmed cardiovascular manifestations post-mRNA COVID-19 vaccination was performed. Following the PRISMA guidelines, electronic databases (PubMed, PMC NCBI, and Cochrane Library) were searched until January 2022. Baseline characteristics of patients and disease outcomes were extracted from relevant studies. RESULTS: A total of 81 articles analyzed confirmed cardiovascular complications post-COVID-19 mRNA vaccines in 17,636 individuals and reported 284 deaths with any mRNA vaccine. Of 17,636 cardiovascular events with any mRNA vaccine, 17,192 were observed with the BNT162b2 (Pfizer-BioNTech) vaccine, 444 events with mRNA-1273 (Moderna). Thrombosis was frequently reported with any mRNA vaccine (n = 13,936), followed by stroke (n = 758), myocarditis (n = 511), myocardial infarction (n = 377), pulmonary embolism (n = 301), and arrhythmia (n = 254). Stratifying the results by vaccine type showed that thrombosis (80.8%) was common in the BNT162b2 cohort, while stroke (39.9%) was common with mRNA-1273 for any dose. The time between the vaccination dosage and the first symptom onset averaged 5.6 and 4.8 days with the mRNA-1273 vaccine and BNT162b2, respectively. The mRNA-1273 cohort reported 56 deaths compared to the 228 with BNT162b2, while the rest were discharged or transferred to the ICU. CONCLUSION: Available literature includes more studies with the BNT162b2 vaccine than mRNA-1273. Future studies must report mortality and adverse cardiovascular events by vaccine types.

No difference in myocardial iron concentration and serum ferritin with deferasirox and deferiprone in pediatric patients with hemoglobinopathies: A systematic review and meta-analysis.

OBJECTIVES: Iron overload is a common complication experienced by transfusion-dependent children with hemoglobin disorders. Chelators such as deferasirox (DFX) and deferiprone (DFP) are effective in overcoming this problem. We conducted this systematic review and meta-analysis to evaluate the effectiveness of DFX compared to DFP in treating iron overload amongst pediatric patients with hemoglobin disorders. MATERIAL AND METHODS: PubMed and Cochrane Central were searched from their inception until Dec 21 2021, for randomized clinical trials (RCTs) and observational studies, which assessed the efficacy of DFX compared to DFP in the treatment of inherited hemoglobin disorders. The outcomes of interest included myocardial iron concentration (MRI T2*) at the end of the trial and change in mean serum ferritin (SF) levels at the 6 and 12 months mark. Weighted mean differences (WMDs) with their corresponding 95% confidence intervals (CIs) were calculated for continuous outcomes using random effects model. RESULTS: A total of 5 studies comprising 607 children were included. The results of our analysis revealed no significant difference between DFX and DFP in MRI T2* at the end of treatment (WMD: -0.92; 95% CI [-3.35, 1.52]; p = 0.46; I2 = 0). Moreover, there has been no significant difference noted in SF levels at both 6 months (WMD: 97.31; 95% CI [-236.16, 430.77]; p = 0.57; I2 = 0) and 12 months (WMD: 46.99; 95% CI [-191.42, 285.40]; p = 0.70; I2 = 0) respectively. CONCLUSION: Our analysis shows no significant difference between the efficacy of DFX and DFP in the management of iron overload in children with inherited blood disorders. Future large-scale clinical trials are required to further validate our results.

Glycolysis: The Next Big Breakthrough in Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by the death of dopaminergic neurons. Its pathogenesis comprises defects in the physiological pathway of mitophagy and mutations in the genes involved in this process's regulatory mechanism. PD manifests itself with multiple motor and non-motor symptoms, and currently, there are multiple pharmacological treatments, and unconventional non-drug treatments available. The mainstay of Parkinson's disease treatment has centered around directly manipulating neural mechanisms to retain high dopamine levels, either by exogenous administration, increasing intrinsic production, or inhibiting the breakdown of dopamine. In this review, we highlight a new potential biochemical modality of treatment, treating PD through glycolysis. We highlight how terazosin (TZ), via PGK1, increases ATP levels and how enhanced glycolysis serves a neuroprotective role in PD, and compensates for damage caused by mitophagy. We also discuss the role of quercetin, a bioactive flavonoid, in preventing the development of PD, and reversing mitochondrial dysfunction but only so in diabetic patients. Thus, further research should be conducted on glycolysis as a protective target in PD that can serve to not just prevent, but also alleviate the non-dopaminergic signs and symptoms of PD.

Apheresis: A cell-based therapeutic tool for the inflammatory bowel disease.

Inflammatory Bowel Disease (IBD) is a hallmark of leukocyte infiltration, followed by the release of cytokines and interleukins. Disease progression to Ulcerative Colitis (UC) or Crohn's Disease (CD) remained largely incurable. The genetic and environmental factors disrupt enteral bacteria in the gut, which hampers the intestinal repairing capability of damaged mucosa. Commonly practiced pharmacological therapies include 5-aminosalicylic acid with corticosteroids and tumor necrosis factor (TNF)-α. New interventions such as CDP571 and TNF-blocking RDP58 report the loss of patient response. This review discusses the non-pharmacologic selective granulocyte-monocyte-apheresis (GMA) and leukocytapheresis (LCAP) that have been proposed as treatment modalities that reduce mortality. GMA, an extracorporeal vein-to-vein technique, presents a strong safety profile case for its use as a viable therapeutic option compared to GMA's conventional medication safety profile. GMA reported minimal to no side effects in the pediatric population and pregnant women. Numerous studies report the efficacious nature of GMA in UC patients, whereas data on CD patients is insufficient. Its benefits outweigh the risks and are emerging as a favored non-pharmacological treatment option. On the contrary, LCAP uses a general extracorporeal treatment that entraps leukocytes and suppresses cytokine release. It has been deemed more efficacious than conventional drug treatments, the former causing better disease remission, and maintenance. Patients with UC/CD secondary to complications have responded well to the treatment. Side effects of the procedure have remained mild to moderate, and there is little evidence of any severe adverse event occurring in most age groups. LCAP decreases the dependence on steroids and immunosuppressive therapies for IBD. The review will discuss the role of GMA and LCAP.

Comparative analysis of neutrophil to lymphocyte ratio and derived neutrophil to lymphocyte ratio with respect to outcomes of in-hospital coronavirus disease 2019 patients: A retrospective study.

Introduction and objectives: In patients with coronavirus disease 2019 (COVID-19), several abnormal hematological biomarkers have been reported. The current study aimed to find out the association of neutrophil to lymphocyte ratio (NLR) and derived NLR (dNLR) with COVID-19. The objective was to compare the accuracy of both of these markers in predicting the severity of the disease. Materials and methods: The study was conducted in a single-center having patients with COVID-19 with a considerable hospital stay. NLR is easily calculated by dividing the absolute neutrophil count (ANC) with the absolute lymphocyte count (ALC) {ANC/ALC}, while dNLR is calculated by ANC divided by total leukocyte count minus ANC {ANC/(WBC-ANC)}. Medians and interquartile ranges (IQR) were represented by box plots. Multivariable logistic regression was performed obtaining an odds ratio (OR), 95% CI, and further adjusted to discover the independent predictors and risk factors associated with elevated NLR and dNLR. Results: A total of 1,000 patients with COVID-19 were included. The baseline NLR and dNLR were 5.00 (2.91-10.46) and 4.00 (2.33-6.14), respectively. A cut-off value of 4.23 for NLR and 2.63 for dNLR were set by receiver operating characteristic (ROC) analysis. Significant associations of NLR were obtained by binary logistic regression for dependent outcome variables as ICU stay (p < 0.001), death (p < 0.001), and invasive ventilation (p < 0.001) while that of dNLR with ICU stay (p = 0.002), death (p < 0.001), and invasive ventilation (p = 0.002) on multivariate analysis when adjusted for age, gender, and a wave of pandemics. Moreover, the indices were found correlating with other inflammatory markers such as C-reactive protein (CRP), D-dimer, and procalcitonin (PCT). Conclusion: Both markers are equally reliable and sensitive for predicting in-hospital outcomes of patients with COVID-19. Early detection and predictive analysis of these markers can allow physicians to risk assessment and prompt management of these patients.

Efficacy and Safety of Concomitant Tricuspid Repair in Patients Undergoing Mitral Valve Surgery: a Systematic Review and Meta-Analysis.

Tricuspid valve repair (TVR) is recommended for patients with moderate primary tricuspid regurgitation (TR), those with moderate TR, and a history of heart failure without annular dilation, while being essential for patients with severe secondary TR undergoing MVS. The meta-analysis aimed to evaluate the efficacy and safety of tricuspid valve repair in patients undergoing MVS. We systematically searched PubMed, Embase, and Google Scholar through January 2022, and studies comparing patients with TVR and those without TVR were selected. The primary outcomes were 30-day, and all-cause mortality. In this meta-analysis, 20 studies were included with a patient population of 72,422. No significant differences were observed between patients undergoing TVR with MVS, in comparison to MVS group only for the primary outcomes i.e., 30-day mortality (RR: 1.14, 95% CI [0.69, 1.87], and all-cause mortality (RR: 1.16, 95% CI [0.86, 1.57]. From the secondary outcomes, pacemaker insertion (RR: 2.62, 95% CI [2.24, 3.06]), new-onset TR or progression (RR: 0.32, 95% CI [0.16, 0.66]), stroke (RR: 1.22, 95% CI [1.05, 1.42]), cross-clamp time (WMD: 17.67, 95% CI [13.96, 21.37]), surgery time (WMD: 43.59, 95% CI [37.07, 50.10]), ICU time (WMD: 19.50, 95% CI [9.31, 29.67]), and ventilation time (WMD: 6.62, 95% CI [0.69, 12.55]) were significant. However, major bleeding events, atrial fibrillation, renal failure, heart failure hospitalization, postoperative MI, wound infection, early or prolonged morbidity, cardiopulmonary bypass time, and duration of hospital stay were non-significant. Our meta-analysis has furthered the discussion for weighing the risks and benefits of pursuing TVR during MVS.

Novel drug delivery systems for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic illness characterized by relapsing inflammation of the intestines. The disorder is stratified according to the severity and is marked by its two main phenotypical representations: Ulcerative colitis and Crohn's disease. Pathogenesis of the disease is ambiguous and is expected to have interactivity between genetic disposition, environmental factors such as bacterial agents, and dysregulated immune response. Treatment for IBD aims to reduce symptom extent and severity and halt disease progression. The mainstay drugs have been 5-aminosalicylates (5-ASAs), corticosteroids, and immunosuppressive agents. Parenteral, oral and rectal routes are the conventional methods of drug delivery, and among all, oral administration is most widely adopted. However, problems of systematic drug reactions and low specificity in delivering drugs to the inflamed sites have emerged with these regular routes of delivery. Novel drug delivery systems have been introduced to overcome several therapeutic obstacles and for localized drug delivery to target tissues. Enteric-coated microneedle pills, various nano-drug delivery techniques, prodrug systems, lipid-based vesicular systems, hybrid drug delivery systems, and biologic drug delivery systems constitute some of these novel methods. Microneedles are painless, they dislodge their content at the affected site, and their release can be prolonged. Recombinant bacteria such as genetically engineered Lactococcus Lactis and eukaryotic cells, including GM immune cells and red blood cells as nanoparticle carriers, can be plausible delivery methods when evaluating biologic systems. Nano-particle drug delivery systems consisting of various techniques are also employed as nanoparticles can penetrate through inflamed regions and adhere to the thick mucus of the diseased site. Prodrug systems such as 5-ASAs formulations or their derivatives are effective in reducing colonic damage. Liposomes can be modified with both hydrophilic and lipophilic particles and act as lipid-based vesicular systems, while hybrid drug delivery systems containing an internal nanoparticle section for loading drugs are potential routes too. Leukosomes are also considered as possible carrier systems, and results from mouse models have revealed that they control anti- and pro-inflammatory molecules.

In silico identification of the rare-coding pathogenic mutations and structural modeling of human NNAT gene associated with anorexia nervosa.

PURPOSE: Increased susceptibility towards anorexia nervosa (AN) was reported with reduced levels of neuronatin (NNAT) gene. We sought to investigate the most pathogenic rare-coding missense mutations, non-synonymous single-nucleotide polymorphisms (nsSNPs) of NNAT and their potential damaging impact on protein function through transcript level sequence and structure based in silico approaches. METHODS: Gene sequence, single nucleotide polymorphisms (SNPs) of NNAT was retrieved from public databases and the putative post-translational modification (PTM) sites were analyzed. Distinctive in silico algorithms were recruited for transcript level SNPs analyses and to characterized high-risk rare-coding nsSNPs along with their impact on protein stability function. Ab initio 3D-modeling of wild-type, alternate model prediction for most deleterious nsSNP, validation and recognition of druggable binding pockets were also performed. AN 3D therapeutic compounds that followed rule of drug-likeness were docked with most pathogenic variant of NNAT to estimate the drugs' binding free energies. RESULTS: Conclusively, 10 transcript (201-205)-based nsSNPs from 3 rare-coding missense variants, i.e., rs539681368, rs542858994, rs560845323 out of 840 exonic SNPs were identified. Transcript-based functional impact analyses predicted rs539681368 (C30Y) from NNAT-204 as the high-risk rare-coding pathogenic nsSNP, deviating protein functions. The 3D-modeling analysis of AN drugs' binding energies indicated lowest binding free energy (ΔG) and significant inhibition constant (Ki) with mutant models C30Y. CONCLUSIONS: Mutant model (C30Y) exhibiting significant drug binding affinity and the commonest interaction observed at the acetylation site K59. Thus, based on these findings, we concluded that the identified nsSNP may serve as potential targets for various studies, diagnosis and therapeutic interventions. LEVEL OF EVIDENCE: No level of evidence-open access bioinformatics research.

Self-Medication Practices in Medical Students During the COVID-19 Pandemic: A Cross-Sectional Analysis.

Background and Objectives: During the pandemic, the growing influence of social media, accessibility of over-the-counter medications, and fear of contracting the virus may have led to self-medication practices among the general public. Medical students are prone to such practices due to relevant background knowledge, and access to drugs. This study was carried out to determine and analyze the prevalence of self-medication practices among medical students in Pakistan. Materials and Methods: This descriptive, cross-sectional study was conducted online in which the participants were asked about the general demographics, their self-medication practices and the reasons to use. All participants were currently enrolled in a medical college pursuing medical or pharmacy degree. Non-probability sampling technique was used to recruit participants. Results: A total of 489 respondents were included in the final analysis. The response rate was 61%. Majority of the respondents were females and 18-20 years of age. Self-medication was quite prevalent in our study population with 406 out of 489 individuals (83.0%) were using any of the drugs since the start of pandemic. The most commonly utilized medications were Paracetamol (65.2%) and multivitamins (56.0%). The reasons reported for usage of these medications included cold/flu, or preventive measures for COVID-19. The common symptoms reported for self-medication included fever (67.9%), muscle pain (54.0%), fatigue (51.7%), sore throat (46.6%), and cough (44.4%). Paracetamol was the most commonly used drug for all symptoms. Female gender, being in 3rd year of medical studies, and individuals with good self-reported health were found more frequent users of self-medication practices. Conclusion: Our study revealed common self-medication practices among medical and pharmacy students. It is a significant health issue especially during the pandemic times, with high consumption reported as a prevention or treating symptoms of COVID-19.