Comparative efficacy and safety of mitral valve repair versus mitral valve replacement in Rheumatic heart disease: A high-value care systematic review and meta-analysis.

Rheumatic Heart Disease (RHD) remains a leading cause of cardiovascular death (CVD) globally. Mitral Valve repair (MVP) and mitral valve replacement (MVR) are the two most commonly and successfully used techniques to treat the disease. MVP is associated with reduced post-operative complications compared to MVR; however, it carries the risk of valvular fibrosis and scarring. Given the lack of recommendations, inconsistent findings, and paucity of pathophysiological evidence at present, we aimed to conduct a meta-analysis and systematically review the available literature to determine the efficacy and safety of MVP compared to MVR in improving clinical outcomes among patients with RHD. A comprehensive literature search was conducted on MEDLINE (PubMed), Cochrane Central and Scopus from inception till September 2023. The primary objective was early mortality defined as any cause-related death occurring 30 days following surgery. Secondary outcomes included long-term survival defined as the time duration between hospital discharge and all-cause death. Infectious endocarditis, thromboembolic events (including stroke, brain infarction, peripheral embolism, valve thrombosis, and transient ischemic attack), and haemorrhagic events (any serious bleeding event that required hospitalisation, resulted in death, resulted in permanent injury, or required blood transfusion) were all considered as post- operative complications. Additionally aggregated Kaplan-Meier curves were reconstructed for long term survival, freedom from reoperation, and freedom from valve-related adverse events by merging the reconstructed individual patient data (IPD) from each individual study. A significant decrease in early mortality with MV repair strategy versus MV replacement [RR 0.63; P = 0.003) irrespective of mechanical or bioprosthetic valves was noted. The results reported significantly higher long-term survival in patients undergoing MVP versus MVR (HR 0.53; P = 0.0009). Reconstructed Kaplan-Meier curves showed that the long term survival rates at 4, 8, and 12 years were 88.6, 82.0, 74.6 %, in the MVR group and 91.7, 86.8, 81.0 %, in the MVP group, respectively. MVP showed statistically significant reduction in early mortality, adverse vascular events, and better long-term survival outcomes compared to the MVR strategy in this analysis.

Efficacy and safety of finerenone in chronic kidney disease and type 2 diabetes patients: a systematic review and meta-analysis.

Background and objectives: The incidence of morbidity and mortality in patients with type 2 diabetes mellitus is substantially correlated with cardiovascular disease and chronic kidney disease. The current guidelines recommend the use of renin-angiotensin system blockers, but recent studies probed into the effects of finerenone to mitigate the risk of cardiorenal events. This meta-analysis was performed to demonstrate the effects of finerenone on cardiorenal events, comprising cardiovascular mortality, heart failure, change in estimated glomerular filtration rate, and serum potassium levels. Methods: After screening with our eligibility criteria, 350 articles were identified with an initial literature search on multiple databases, including PubMed, Science Direct, and Cochrane Central. Seven randomized controlled trials with a total of 15 462 patients (n=8487 in the finerenone group; n=6975 in the control group) were included. Results: Patients receiving finerenone were at a reduced risk for cardiovascular mortality [HR: 0.84 (0.74, 0.95)], heart failure [OR: 0.79 (0.68, 0.92)], decrease in estimated glomerular filtration rate by 40% [OR: 0.82 (0.74, 0.91)] and by 57% [OR: 0.70 (0.59, 0.82)]; and a higher incidence of moderate hyperkalemia [OR: 2.25 (1.78, 2.84)]. Conclusion: Finerenone, owing to its better mineralocorticoid affinity, and a much lower risk of adverse effects, promises to be a much better alternative than other renin-angiotensin system blockers available for the treatment of chronic kidney disease patients with type 2 diabetes. Further trials should be conducted to provide more definitive evidence to assess the safety and efficacy of finerenone compared to spironolactone and eplerenone.

Caregiver's perceptions of COVID-19 vaccination, and intention to vaccinate their children against the disease: a questionnaire based qualitative study.

Coronavirus disease 2019 (COVID-19) vaccine side effects have an important role in the hesitancy of the general population toward vaccine administration. Another reason for vaccine hesitancy might be that healthcare professionals may not address their concerns regarding vaccines appropriately. Regardless, hesitancy in the form of delay, refusal, or acceptance with doubts about its usefulness can limit the downward trajectory of the COVID-19 pandemic. Therefore, the authors conducted a national cross-sectional study (n=306) to assess causes and concerns for vaccine hesitancy in caregivers in Pakistan toward getting their children vaccinated. The questions identified caregivers by socioeconomic demographics, perceived COVID-19 pandemic severity, and concerns toward the COVID-19 vaccine. The majority of the participants were 45-59 years of age (42.8%) with a mean age of 36.11 years (SD: 7.81). A total of 80% of these participants were willing to vaccinate their child with any COVID-19 vaccine. Present comorbidities had a frequency of 28.4% (n=87/306) and only 26.9% (n=66/245) participants were willing to vaccinate their child. Participants with high social standing were 15.4% (n=47/306) with the majority of them being willing to vaccinate their children (45/47). Socioeconomic status (OR:2.911 [0.999-8.483]), and the child's vaccinations being up to date (OR:1.904 [1.078-3.365]) were found to be independent factors for caregivers to be willing to vaccinate their child. Around 62% (n=191/306) were not willing to vaccinate due to the concern for side effects, 67.6% (n=207/306) were not willing because they did not have ample information available, and 51% (n=156/306) were not willing as they were concerned about vaccine effectiveness. Further studies on vaccine safety in the pediatric population are required to improve caregivers' perceptions.

Association of neutrophil-to-lymphocyte ratio with clinical, pathological, radiological, laboratory features and disease outcomes of invasive breast cancer patients: A retrospective observational cohort study.

Inflammatory conditions play part in the progression of malignancies, and markers signifying growth of these factors can indicate prognosis. Neutrophil-to-lymphocyte (NLR) is used as a marker of subclinical inflammation that may become an integral part of workup to indicate prognosis and associated pathology. This study aims to explore the association of NLR ratio with clinical characteristics, radiological assessment and staging, histopathology, and disease outcomes of breast cancer. A retrospective cohort study was conducted in a tertiary care center to include breast cancer patients that were diagnosed between January 2001 and December 2020. Data including tumor size, lymph nodes, metastasis, histological grading, ER/PR/HER2-neu status, molecular subtypes, clinical staging); nodal findings (sentinel and axillary); pathology from frozen section; and disease outcomes were assessed. Multivariable regression and Kaplan-Meier survival curves were employed to indicate the association of NLR with breast cancer features and disease-free survival. A total of 2050 patients had a median age of 50 years, median NLR levels of 2.14, most common pathology ductal followed by lobular, and most common site of metastasis being lungs followed by bones. Disease-free rate was 7.6%, and a recurrence rate of 1.8%, while 1.6% deaths were reported. NLR was found associated with age, treatment outcomes, tumor size, lymph nodes, metastasis and clinical staging. Other positive correlations were with Ki67 proliferation index, molecular subtypes, and tumor size on frozen section (at transverse and craniocaudal dimensions). Negative correlations were seen with estrogen and progesterone receptors. However, NLR was not found predictable of disease-free survival (P = .160). Significant predictors of disease-free survival were histological grading, ER, PR status, molecular subtype, and Ki67 proliferation index. NLR being a readily available marker has shown novel findings in its association with tumor staging, disease outcomes and characteristics of breast malignancy.

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.

Frequency of COVID-19 vaccine side effects and its associated factors among the vaccinated population of Pakistan: A cross-sectional study.

Background: Coronavirus disease 2019 (COVID-19) vaccine side effects have an important role in the hesitancy of the general population toward vaccine administration. Therefore, this study was conducted to document the COVID-19 vaccine side effects in our population. Materials and Methods: An online survey-based, cross-sectional study was carried out from September 1, 2021, to October 1, 2021, to document the side effects of the COVID-19 vaccine among the general public. The questionnaire included participants' sociodemographic data, type of vaccine, comorbidities, previous COVID-19 infection, and assessment of side effects reported by them. Results: The majority of the participants were <20 years of age (62.2%), females (74.9%), belonged to the educational sector (58.1%), residents of Sindh (65.7%), and were previously unaffected by COVID-19 infection (73.3%). Sinovac (38.7%) followed by Sinopharm (30.4%) and Moderna (18.4%) were administered more frequently. Commonly reported side effects were injection site pain (82%), myalgia (55%), headache (46%), fatigue/malaise (45%), and fever (41%). Vaccine side effects were more likely to be reported with the first dose as compared to the second dose. On regression analysis, factors associated with occurrence of side effects included younger age (odds ratio [OR]: 6.000 [2.065-17.431], p < 0.001), female gender (OR: 2.373 [1.146-4.914], p = 0.020), marital status (OR: 0.217 [0.085-0.556], p < 0.001), graduate level of education (OR: 0.353 [0.153-0.816], p = 0.015), and occupation being either retired, freelancers, or social workers (OR: 0.310 [0.106-0.909]), p = 0.033). Previous infection with COVID-19 (p = 0.458) and comorbidities were found unrelated (p = 0.707) to the occurrence of side effects. Conclusion: The overall prevalence of local side effects was quite higher than the systemic ones. Further large-scale studies on vaccine safety are required to strengthen public confidence in the vaccination drive.

Current Practices and Considerations for Transcatheter Mitral Valve Implantation Based on Risk Stratification Among Patients with Mitral Valve Regurgitation.

Mitral Regurgitation (MR) is the most common form of severe valvular disease occurring in developed countries, being caused either primarily on its own or secondary to cardiac disease. Surgical intervention is required for the correction of MR, which could include the replacement or repair of the affected valve. Transcatheter Mitral Valve Replacement (TMVR) in selected patients is of increasing importance, especially after the success of Transcatheter Aortic Valve Replacement. TMVR can be divided into 3 types, that is, valve-in-valve for severe mitral valve disease, valve-in-ring for failed surgical repairs, and valve-in-mitral annular calcifications for mitral valvular disease with severe mitral annular calcifications and poor surgical criteria. The FDA approved Mitral valve-in-valve for patients with a high surgical risk in 2017, while valve-in-ring and valve-in-mitral annular calcifications are still currently under consideration. The SAPIEN M3 valve is relatively new with a trans-septal system, with a success rate of 86%, and no mortality in a 30-day outcome. The Cardiovalve is a bovine pericardium device that has a dual nitinol frame with a custom surgical design to facilitate TMVR. The AHEAD trial will evaluate whether the device is safe to use in a clinical setting and how effective it is for reducing MR in these patients. The trial consists of 30 patients in which the first 5 patients showed 100% technical success and a reduction of MR. This evolution of modern medicine has assisted in many different countries, including Pakistan where there is a higher prevalence of MR and hence, a greater need to apply TMVR in clinical practice.

Early Transcatheter or Surgical Aortic Valve Replacement Versus Conservative Management in Asymptomatic Patients With Severe Aortic Stenosis: A Systematic Review and Meta-analysis.

The merits of conservative management vs early intervention in patients with asymptomatic severe aortic stenosis remains unknown. Digital databases (MEDLINE, Google Scholar, and Embase) were searched for all relevant studies from inception through September 2022. Studies comparing conservative management with early intervention were compared using a random-effects model to calculate risk ratios (RRs) with 95% confidence interval (CI). A total of 12 studies comprising 3624 asymptomatic aortic stenosis patients (1747 receiving surgery, and 1877 receiving conservative treatment) were included in the analysis. The average follow-up time was 4.45 (IQR 3.5-5) years. Early intervention was associated with a significantly reduced risk of cardiac (RR 0.42, 95% CI 0.25-0.72; P = 0.001; I2 = 54%), non-cardiac (RR 0.46, 95% CI 0.32-0.68; P < 0.0001; I2 = 0%), all-cause mortality (RR 0.40, 95% CI 0.32-0.51; P < 0.00001; I2 = 58%), heart failure hospitalization (RR 0.21, 95% CI 0.13-0.36; P < 0.00001; I2 = 0%), sudden cardiac death (RR 0.29, 95% CI 0.12-0.66; P = 0.004, I2 = 24%), and MACE (RR 0.46, 95% CI; 0.28-0.75; P = 0.002; I2 = 68%), compared with conservative management. There was no significant difference in the 30-day mortality (RR 0.63, 95% CI 0.19-2.04; P = 0.44; I2 = 28%), myocardial infarction (RR 0.44, 95% CI 0.19-1.06; P = 0.07, I2=0%), and 90-day mortality (RR 0.68, 95% CI 0.20-2.37; P = 0.55; I2 = 61%) between the 2 groups. This meta-analysis shows statistically significant reductions in the risk for all-cause mortality, cardiac specific mortality, non-cardiac mortality, heart failure hospitalization, MACE, and sudden cardiac death among asymptomatic aortic stenosis patients who underwent early intervention as opposed to conservative management.

Long-Term Efficacy and Safety of Left Atrial Appendage Occlusion (LAAO) vs Direct Oral Anticoagulation (DOAC) in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background: Prevention of stroke by anticoagulation is essential in patients with Atrial fibrillation (AF); with direct oral anticoagulants (DOACs) being preferred over warfarin in most patients. The Long-term efficacy and safety of DOACs vs. Left Atrial Appendage Occlusion (LAAO) remain unknown. Methods: Electronic databases (PubMed, Embase, Scopus) were searched from inception to February 10th, 2021. The primary endpoint was cardiovascular mortality. Secondary outcomes included incidence of ischemic stroke/transient ischemic attack (TIA) and systemicembolism. The safety endpoint was clinically relevant bleeding (a composite of major or minor clinically relevant bleeding). Results: A total of three studies with 3039 participants (LAAO = 1465; DOACs = 1574) were included. Mean age was 74.2 and 75.3 years in the LAAO and DOAC group respectively. Average follow-up period was 2 years. There was no difference in terms of cardiac mortality (RR 0.90, 95% CI 0.40-2.03; p = 0.81), ischemic stroke/TIA (RR 1.15, 95% CI 0.80-1.65; p = 0.46; I 2 = 0) and clinically significant bleeding (RR 0.77, 95% CI 0.50-1.17; p = 0.22; I 2 = 69) between the groups. Conclusions: Among patients with AF, LAAO was comparable to DOACs with similar efficacy and safety profiles.

Patient-Centered Therapy for Obstructive Sleep Apnea: A Review.

Obstructive sleep apnea (OSA) is one of the most common sleep problems defined by cessation or decreased airflow despite breathing efforts. It is known to be related to multiple adverse health consequences. Positive airway pressure (PAP) is considered an effective treatment that is widely used. Various modes of PAP and other emerging treatment options are now available. A multidisciplinary approach, understanding diverse phenotypes of OSA, and shared decision-making are necessary for successful OSA treatment. Patient-centered care is an essential modality to support patient care that can be utilized in patients with OSA to help improve outcomes, treatment adherence, and patient satisfaction.

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.

The Menace of Candida auris Epidemic Amidst the COVID-19 Pandemic: A Systematic Review.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent for the Coronavirus Disease 2019 (COVID-19) pandemic, has sparked a medical emergency worldwide. With the rise in COVID-19 infections and an eventual increase in hospitalized critically ill patients, a trend of bacterial, fungal, and viral superinfection has been noted. One important agent of co-infection identified is Candida auris. Due to its multidrug-resistant nature and easy transmissibility, C. auris is difficult to manage in COVID-positive patients. Patients with comorbidities, immunosuppressive states, intubated and on ventilators are more likely to contract the fungal infection. Therefore, it is essential to the first screen, diagnose, and isolate patients with C. auris infection and manage and treat them while preventing the spread of the disease. Failure to recognize and prevent its spread may lead to an eventual epidemic or even a pandemic during the current COVID-pandemic, which the exhausted healthcare system can most definitely not handle. This systematic review investigates the prevalence of C. auris, its pathophysiology, diagnosis, prevention, and treatment during the COVID-19 pandemic.

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.

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.

Willingness and Perceptions Regarding COVID-19 Vaccine Booster Dose in Pakistani Vaccinated Population: A Cross-Sectional Survey.

Objectives: This study was conducted to evaluate COVID-19 vaccine booster dose willingness and identify predictors and factors of willingness and hesitance in the vaccinated population of Pakistan. Methods: A cross-sectional web-based survey was undertaken between January and February 2022 to highlight the public perceptions regarding the COVID-19 booster dose and evaluate the willingness to get the additional dose. Demographic information and booster dose willingness were recorded through the questionnaire. Additionally, a 5-point Likert scale was employed to explore fears and beliefs regarding COVID-19 vaccinations. Univariate and multivariate regression was performed to identify booster dose willingness and hesitance factors. Results: Of the 787 respondents, 69.6% were females, 75.3% fell in the 18-30 years age group, 53.5% were university students or had a Bachelor's degree. Overall, a 77.8% booster dose willingness was reported. Participants showed absence or low fear levels associated with a booster dose (47.3%). 60.1% agreed it was safe to receive an additional vaccine dose, with 44.1% agreeing that boosters are effective against coronavirus variants. Independent predictors of willingness included the absence of comorbidities, whereas not being willing to pay for the booster dose was a predictor of hesitance. Conclusion: This study showed a suboptimal willingness level of booster dose uptake among the vaccinated Pakistani population. Public health policymakers must undertake necessary awareness campaigns to strategize vaccination drives and dispel myths.

Emerging role of biosimilars in the clinical care of inflammatory bowel disease patients.

The increasing incidence of inflammatory bowel disease (IBD) globally has redirected the healthcare system's focus towards safe and affordable pharmacological interventions. The inception of anti-tumor necrosis factor-α (TNF-α) had resulted in a trend shift from surgical interventions. However, as the patents of approved anti-TNF-α drugs expire, biological copies of the many approved products are in the pipeline. The most commonly used biosimilar for IBD has been infliximab, followed by Adalimumab biosimilars which have been approved in major countries across the world. Although biosimilars are approved on the basis of similarity of their reference product, the lack of real-world evidence of its safety in ulcerative colitis and Crohn's disease patients has contributed to physicians' hesitancy. However, biosimilars are expected to reduce treatment costs and provide economic benefits.

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.