Androgen Signaling in Prostate Cancer: When a Friend Turns Foe.

Androgen (AR) signaling is the main signaling for the development of the prostate and its normal functioning. AR is highly specific for testosterone and dihydrotestosterone, significantly contributing to prostate development, physiology, and cancer. All these receptors have emerged as crucial therapeutic targets for PCa. In the year 1966, the Noble prize was awarded to Huggins and Hodge for their groundbreaking discovery of AR. As it is a pioneer transcription factor, it belongs to the steroid hormone receptor family and consists of domains, including DNA binding domain (DBD), hormone response elements (HRE), C-terminal ligand binding domain (LBD), and N-terminal regulatory domains. Structural variations in AR, such as AR gene amplification, LBD mutations, alternative splicing of exons, hypermethylation of AR, and co- regulators, are major contributors to PCa. It's signaling is crucial for the development and functioning of the prostate gland, with the AR being the key player. The specificity of AR for testosterone and dihydrotestosterone is important in prostate physiology. However, when it is dysregulated, AR contributes significantly to PCa. However, the structural variations in AR, such as gene amplification, mutations, alternative splicing, and epigenetic modifications, drive the PCa progression. Therefore, understanding AR function and dysregulation is essential for developing effective therapeutic strategies. Thus, the aim of this review was to examine how AR was initially pivotal for prostate development and how it turned out to show both positive and detrimental implications for the prostate.

Comparative Outcomes of Peritoneal and Hemodialysis in ESRD Patients with STEMI: A National Inpatient Sample Analysis (2016-2020).

End-stage renal disease (ESRD) patients are at increased risk of mortality, particularly due to cardiovascular events such as acute myocardial infarction. Hemodialysis and peritoneal dialysis are the two main treatment modalities for ESRD patients. Using data from the National Inpatient Sample (NIS) database, we conducted a retrospective study involving 25,435 ESRD patients diagnosed with ST-elevation myocardial infarction (STEMI) between 2016 and 2020, categorized by their dialysis regimen. Our analysis revealed comparable mortality rates between peritoneal dialysis (PD) and hemodialysis (HD) patients, but lower hospitalization costs and fewer complications among PD recipients. Over five years, we observed a notable decrease in STEMI mortality despite increased STEMI cases among HD patients. Conversely, HD patients experienced increased hospital stays and associated costs over the study period than PD patients, who demonstrated stable trends. This study highlights the implications of dialysis modality selection in managing costs and reducing morbidity among STEMI patients with ESRD.

Genetic diversity, spatial connectivity, and population structure of Asian silurid catfish Wallago attu (Bloch and Schneider, 1801) in the Ganga River System: insights from mitochondrial DNA analysis.

BACKGROUND: The Ganga River System (GRS) is a biodiversity hotspot, its ecological richness is shaped by a complex geological history. In this study, we examined the genetic diversity, spatial connectivity, and population structure of the Asian Silurid catfish, Wallago attu, across seven tributaries of the GRS. METHODS AND RESULTS: We employed three mitochondrial DNA (mtDNA) regions: cytochrome c oxidase subunit I (COXI), cytochrome b (Cyt b), and control region (CR). Our comprehensive dataset encompassed 2420 bp of mtDNA, derived from 176 W. attu individuals across 19 sampling sites within the seven rivers of GRS. Our findings revealed high gene diversity (Hd:0.99) within W. attu populations. Analysis of Molecular Variance (AMOVA) highlighted that maximum genetic variations were attributed within the populations, and the observed genetic differentiation among the seven populations of W. attu ranged from low to moderate. Network analysis uncovered the presence of three distinct genetic clades, showing no specific association with seven studied rivers. Bayesian skyline plots provided insights into the demographic history of W. attu, suggesting a recent population expansion estimated to have occurred approximately 0.04 million years ago (mya) during the Pleistocene epoch. CONCLUSIONS: These results significantly enhance our understanding of the genetic diversity and spatial connectivity of W. attu, serving as a vital foundation for developing informed conservation strategies and the sustainable management of this economically valuable resource within the Ganga River System.

Effect of GA3 and calcium on growth, biochemical, and fatty acid composition of linseed under chloride-dominated salinity.

The accumulation of salts in soil is an environmental threat affecting plant growth and crop yield. Linseed or flax is an ancient crop that has multifarious utilities in terms of industrial oil, textile fiber, and products. Salt susceptibility adversely affects linseed production, particularly to meet the growing demand for nutritional and nutraceutical products. In the present study, the ameliorative potential of gibberellic acid (GA3) and calcium (Ca2+) in mitigating the adverse effects of chloride-dominated salinity stress on the growth and physiological and biochemical processes in linseed was determined. Severe salinity treatment (10 dSm-1) resulted in stunted growth of tested linseed genotypes causing a significant reduction in biomass while proline content, phenol, H2O2, lipid peroxidation, and DPPH activity were increased in comparison to control. The exogenous application of 10-6 M GA3 and/or 10 mg CaCl2 kg-1 was found to mitigate the adverse effects of salinity stress. The mitigation was accomplished through the improvement of growth indicators, increased osmoprotectants such as proline and phenol content, stimulating DPPH activity, and reduction of H2O2 content and lipid peroxidation. The comparative evaluation of different saline treatments imposed individually and in combination with GA3 and Ca2+ revealed that combined GA3 and Ca2+ application exhibited synergistic effects and was most effective in mitigating the negative impacts of salt stress. The present study unravels the ameliorative role of GA3 and Ca2+ (individual or combined) in the physiologic-biochemical adaptive response of linseed plants grown under chloride-dominated salinity and thus aids in a better understanding of the underlying tolerance mechanisms of plants to withstand stress in saline environments.

Assessing 30-day readmissions and outcomes in acute heart failure patients with concurrent COVID-19: A nationwide study during the 2020 pandemic.

BACKGROUND: Acute heart failure (HF) is a significant cause of readmission and mortality, particularly within 30 days post-discharge. The interplay between COVID-19 and HF is still being studied. METHODS: This retrospective study utilized The National Readmission Database to examine outcomes and predictors among patients with COVID-19 and concomitant acute HF between January 1, 2020, and November 31, 2020. 53,336 index hospitalizations and 8,158 readmissions were included. The primary outcome was the 30-day all-cause readmission rate. Predictor variables included patient demographics, medical comorbidities and discharge disposition. RESULTS: The primary outcome was 21.2 %. COVID-19 infection was the most predominant all-cause reason for acute HF readmission (24.7 %). Hypertensive heart disease with chronic kidney disease was the most prevalent cardiac cause (7.7 %). Mortality rate during index hospitalization was significantly higher compared to readmission. CONCLUSIONS: The highlighted prevalent complications, comorbidities, and demographics driving readmissions offer valuable insights to improve outcomes in this population.

Second stem cell transplantation for treatment of relapsed/refractory multiple myeloma after first autologous stem cell transplant: A 15-year retrospective institutional analysis.

Background: Multiple myeloma remains an incurable disease, with the majority of patients relapsing after autologous stem cell transplant (ASCT). After relapse, second transplant remains one of the therapeutic options, along with novel agents. Methods: We reviewed the data of our patients who underwent ASCT for myeloma (N = 202) over the last two decades (2004-2019). Of these, 12 patients underwent a second transplant. Results: Out of 12 patients, nine underwent second autologous stem cell transplant, whereas three received an allogeneic stem cell transplantation (Allo-SCT). Median progression-free survival (PFS) after the first ASCT was 32 months (5-84 months). Median interval between both the transplants was 35 months (4-159 months). Median age of our cohort which underwent second transplant was 56 years. Overall response rate (ORR) post-second transplant on day +100 was 83.3%, without any transplant-related mortality (TRM). With the use of preemptive plerixafor, none of our patients required a second day for stem cell harvest. Median CD34 dose of stem cells infused was 4.11 × 106/kg. Similar to the first ASCT, the median time to neutrophil and platelet engraftment was 11 and 12 days, respectively. At a median follow-up of 41 months, estimated 3-year PFS and overall survival (OS) was 37% ± 15% and 63% ± 15%, respectively. Conclusion: ">Among all relapsed myeloma patients who were transplant eligible, 11% underwent a second transplant. Second transplant is well tolerated with similar time to engraftment after first ASCT. Hence, we believe that second transplant is a feasible, cost-effective option in a resource-limited setting, which should be more widely utilized.

Development of an Anthropomorphic Heterogeneous Female Pelvic Phantom and Its Comparison with a Homogeneous Phantom in Advance Radiation Therapy: Dosimetry Analysis.

BACKGROUND: Accurate dosimetry is crucial in radiotherapy to ensure optimal radiation dose delivery to the tumor while sparing healthy tissues. Traditional dosimetry techniques using homogeneous phantoms may not accurately represent the complex anatomical variations in cervical cancer patients, highlighting the need to compare dosimetry results obtained from different phantom models. PURPOSE: The aim of this study is to design and evaluate an anthropomorphic heterogeneous female pelvic (AHFP) phantom for radiotherapy quality assurance in cervical cancer treatment. MATERIALS AND METHOD: Thirty RapidArc plans designed for cervical cancer patients were exported to both the RW3 homogeneous phantom and the anthropomorphic heterogeneous pelvic phantom. Dose calculations were performed using the anisotropic analytic algorithm (AAA), and the plans were delivered using a linear accelerator (LA). Dose measurements were obtained using a 0.6 cc ion chamber. The percentage (%) variation between planned and measured doses was calculated and analyzed. Additionally, relative dosimetry was performed for various target locations using RapidArc and IMRT treatment techniques. The AHFP phantom demonstrated excellent agreement between measured and expected dose distributions, making it a reliable quality assurance tool in radiotherapy. RESULTS: The results reveal that the percentage variation between planned and measured doses for all RapidArc quality assurance (QA) plans using the AHFP phantom is 10.67% (maximum value), 2.31% (minimum value), and 6.89% (average value), with a standard deviation (SD) of 2.565 (t = 3.21604, p = 0.001063). Also, for the percentage of variation between homogeneous and AHFP phantoms, the t-value is -11.17016 and the p-value is <0.00001. The result is thus significant at p < 0.05. We can see that the outcomes differ significantly due to the influence of heterogeneous media. Also, the average gamma values in RapidArc plans are 0.29, 0.32, and 0.35 (g ≤ 1) and IMRT plans are 0.45, 0.44, and 0.42 (g ≤ 1) for targets 1, 2, and 3, respectively. CONCLUSION: The AHFP phantom results show more dose variability than homogenous phantom outcomes. Also, the AHFP phantom was found to be suitable for QA evaluation.

Comparison of intravascular ultrasound, optical coherence tomography, and conventional angiography-guided percutaneous coronary interventions: A systematic review, network meta-analysis, and meta-regression.

BACKGROUND: Intracoronary imaging modalities, including intravascular ultrasound (IVUS) and optical coherence tomography (OCT), provide valuable supplemental data unavailable on coronary angiography (CA) and have shown to improve clinical outcomes. We sought to compare the clinical efficacy of IVUS, OCT, and conventional CA-guided percutaneous coronary interventions (PCI). METHODS: Frequentist and Bayesian network meta-analyses of randomized clinical trials were performed to compare clinical outcomes of PCI performed with IVUS, OCT, or CA alone. RESULTS: A total of 28 trials comprising 12,895 patients were included. IVUS when compared with CA alone was associated with a significantly reduced risk of major adverse cardiovascular events (MACE) (risk ratio: [RR] 0.74, 95% confidence interval: [CI] 0.63-0.88), cardiac death (RR: 0.64, 95% CI: 0.43-0.94), target lesion revascularization (RR: 0.68, 95% CI: 0.57-0.80), and target vessel revascularization (RR: 0.64, 95% CI: 0.50-0.81). No differences in comparative clinical efficacy were found between IVUS and OCT. Rank probability analysis bestowed the highest probability to IVUS in ranking as the best imaging modality for all studied outcomes except for all-cause mortality. CONCLUSION: Compared with CA, the use of IVUS in PCI guidance provides significant benefit in reducing MACE, cardiac death, and revascularization. OCT had similar outcomes to IVUS, but more dedicated studies are needed to confirm the superiority of OCT over CA.

Association of Hypoalbuminemia With Clinical Outcomes in Patients Admitted With Acute Heart Failure.

Albumin is a protein produced by the liver essential for maintaining blood volume and regulating fluid balance. Hypoalbuminemia is characterized by low levels of albumin in the blood. It is also a marker of malnutrition-inflammatory syndrome. Several studies have demonstrated its prognostic role in patients with chronic heart failure; however, data regarding hypoalbuminemia in acute heart failure admissions are scarce. This study aims to analyze the relationship between hypoalbuminemia and heart failure. We used a retrospective cohort study surveying data from the 2016-2018 combined National Inpatient Sample (NIS) database. Adult hospitalizations for heart failure patients were identified using the ICD-10 codes, stratified into cohorts with and without hypoalbuminemia. Primary outcomes were (1) in-patient mortality, (2) length of stay, and total hospital charge. We also reclassified the HF admissions with hypoalbuminemia to those with systolic or diastolic heart failure to compare any differences in mortality and other in-patient complications. Multivariate linear and logistic regression were used to adjust for confounders and to analyze the outcomes. There were 1,365,529 adult hospitalizations for Congestive Heart Failure (CHF), and among them 1,205,990 (88 %) had secondary diagnoses of hypoalbuminemia. Patients with comorbid hypoalbuminemia were, on average, 8 years older (P < 0.001), predominantly white race, and males (P-value <0.001). HF hospitalizations with hypoalbuminemia had double in-hospital mortality than those without (4.8% vs 2.7%, P < 0.001). However, there was no difference in mortality between patients with Systolic heart failure and Diastolic heart failure with concomitant low albumin levels (from 4.9 % vs 4.7%, P 0.13). We found that patients admitted with HF and concomitant Hypoalbuminemia (HA) had nearly twice the odds of in-patient mortality than those with normal albumin levels. The Length of Stay (LOS) was higher between comparison groups. THC remained statistically indifferent in patients regardless of albumin levels but was greater in hypoalbuminemic patients with Systolic heart failure than Diastolic heart failure ones.

Association between the Distribution of Adipose Tissue and Outcomes in Acute Pancreatitis: A Comparison of Methods of Fat Estimation.

Purpose To assess the correlation between abdominal fat measured at computed tomography (CT) and dual-energy X-ray absorptiometry (DXA) and association with clinical outcomes in patients with acute pancreatitis (AP). Methods This prospective study comprised consecutive patients with AP who underwent abdominal CT and DXA. Fat estimation was done on whole-body DXA and abdominal CT. Correlations among body mass index (BMI), waist circumference (WC), DXA, and CT fat measurements were determined. The association between fat measurements and clinical outcomes was assessed. Results Fifty-nine patients (mean age 38.2 years, 48 males) were included. There was a strong correlation ( r = 0.691-0.799) between DXA and CT fat estimation. In addition, there was a significant association of the visceral adipose tissue (VAT) on DXA and CT with the severity of AP ( p = 0.039 and 0.021, respectively) and the need for drainage of collections ( p = 0.026 and 0.008, respectively). There was a weak correlation of the BMI and WC with the length of hospitalization (LOH) ( r = 0.121, 0.190, respectively) and length of intensive care unit stay (LOICU) ( r = 0.211, 0.197), while there was a moderate to strong correlation of the truncal fat and visceral fat on DXA and total adipose tissue and VAT on CT with LOH ( r = 0.562, 0.532, 0.602 and 0.614, respectively) and LOICU ( r = 0.591, 0.577, 0.636, and 0.676, respectively). Conclusion In conclusion, fat indices measured on DXA and CT are associated with the severity of AP. In addition, the fat measurements at DXA are strongly correlated with those obtained at CT.

Prevalence and predictors of non-rheumatic valvular heart disease in patients with sickle cell disease: insights from the National In-Patient Database in 2016 and 2017.

Sickle cell disease (SCD) life expectancy has increased in high-income countries, approaching the fifth decade in the United States. Aging in SCD has raised concerns about chronic organ damage due to adaptative and maladaptive cardiac remodeling. This study aims to assess the prevalence and predictors of non-rheumatic valvular heart disease (NRVHD) in SCD patients using the United States National Inpatient Sample database from 2016 and 2017. We conducted a weighted analysis on SCD patients during their index hospitalization. We obtained the prevalence of NRVHD and calculated adjusted odds ratios to identify the associated demographic, social, and clinical characteristics using multivariable logistic regression. We identified 192,460 SCD admissions during 2016 and 2017. Of them, 2450 (1.3%) had NRVHD. Mitral insufficiency (MI) was the most common NRVHD present in 52% of the cases. Mitral valve prolapse represented 12.4%, while aortic stenosis and aortic insufficiency in 10.8% and 12.7%, respectively. Right-sided NRVHD had a lower prevalence, with 17.1% of patients having tricuspid insufficiency (TI) and 6.3% pulmonary insufficiency. There were no cases of mitral, tricuspid, or pulmonary stenosis. Characteristics associated with the presence of NRVHD in SCD were secondary pulmonary hypertension, congestive heart failure, chronic kidney disease, and female sex. NRVHDs, especially MI and TI, are comorbidities in SCD. Literature is scarce on this topic. The predictors found for its occurrence could help address modifiable factors that can positively affect patients with SCD who, due to the natural history of the disease, are at risk of developing NRVHD.

Insights into seasonal-variability of SVOCs, morpho-elemental and spectral characteristics of PM2.5 collected at a dense industrial site: Faridabad, Haryana, India.

The development-oriented anthropogenic activities have led to intensive increase in emission of various organic pollutants, which contribute considerably to human health risk. In the present study, chemical, physical and spectral characterisation of fine particulate matter (PM2.5), collected at Faridabad city, in northern India, were examined. Seasonal variation of organic compounds [n-alkanes, polyaromatic hydrocarbons (PAHs) and phthalic acid esters (PAEs)], and potential health risk of Polyaromatic hydrocarbons (PAHs) exposure using toxic equivalency potential (TEQ) approach had been assessed. These showed seasonal average values ranging from 156.4 ± 57.0 ng/m3 to 217.6 ± 72.9 ng/m3, 98.0 ± 21.4 ng/m3 to 177.8 ± 72.8 ng/m3, and 30.9 ± 11.9 ng/m3 to 82.5 ± 29.2 ng/m3, respectively, with the highest value for winter. It is noteworthy that unlike, n-alkanes and PAEs, PAHs were least during spring. The high molecular weight PAHs (BaP, BkF, DahA and IcdP) were found to exhibit higher TEQ values (ranging from 0.7 to 9.7) despite of their lower concentrations. The PAH diagnostic ratio, carbon preference index and total index revealed the enhanced impact of biogenic sources of emissions in comparison to diesel emission sources during winter.

Silicon photonics interfaced with microelectronics for integrated photonic quantum technologies: a new era in advanced quantum computers and quantum communications?

Silicon photonics is rapidly evolving as an advanced chip framework for implementing quantum technologies. With the help of silicon photonics, general-purpose programmable networks with hundreds of discrete components have been developed. These networks can compute quantum states generated on-chip as well as more extraordinary functions like quantum transmission and random number generation. In particular, the interfacing of silicon photonics with complementary metal oxide semiconductor (CMOS) microelectronics enables us to build miniaturized quantum devices for next-generation sensing, communication, and generating randomness for assembling quantum computers. In this review, we assess the significance of silicon photonics and its interfacing with microelectronics for achieving the technology milestones in the next generation of quantum computers and quantum communication. To this end, especially, we have provided an overview of the mechanism of a homodyne detector and the latest state-of-the-art of measuring squeezed light along with its integration on a photonic chip. Finally, we present an outlook on future studies that are considered beneficial for the wide implementation of silicon photonics for distinct data-driven applications with maximum throughput.

Interference of hemoglobin variants in HbA1c quantification.

Fasting blood glucose and glycated hemoglobin (HbA1c) are routine biomarkers to screen and monitor diabetes mellitus. HbA1c results from glycation at the N-terminus of the ß globin chain of tetrameric human hemoglobin. Fasting blood glucose level varies with the nature and amount of food intake, physical exercise, etc., and, accordingly, is a short-term measure of glucose control. In contrast, HbA1c provides an average measure of glucose control for the long-term (8-12 weeks). Unfortunately, genetic variants of hemoglobin may interfere with HbA1c quantification using ion exchange chromatography, capillary electrophoresis, immunoassay and boronate affinity chromatography. Mass spectrometry, however, measures total glycation of hemoglobin across both α and ß globin chains and correlates well with the ion exchange based method. Additionally, mass spectrometry based quantification is not impacted by the presence of genetic variants of hemoglobin and thus might be a better analytical choice for diabetes mellitus.

Tyrosine kinase inhibitor-associated ventricular arrhythmias: a case series and review of literature.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have been increasingly used as first-line therapy in hematologic and solid-organ malignancies. Multiple TKIs have been linked with the development of cardiovascular complications, especially atrial arrhythmias, but data on ventricular arrhythmias (VAs) is scarce. METHODS: Herein we describe five detailed cases of VAs related to TKI use in patients with varied baseline cardiovascular risk factors between 2019 and 2022 at three centers. Individual chart review was conducted retrospectively. RESULTS: Patient ages ranged from 43 to 83 years. Three patients were on Bruton's TKI (2 ibrutinib and 1 zanubrutinib) at the time of VAs; other TKIs involved were afatinib and dasatinib. Three patients had a high burden of non-sustained ventricular tachycardia (NSVT) requiring interventions, whereas two patients had sustained VAs. While all patients in our case series had significant improvement in VA burden after TKI cessation, two patients required new long-term antiarrhythmic drug therapy, and one had an implantable defibrillator cardioverter (ICD) placed due to persistent VAs after cessation of TKI therapy. One patient reinitiated TKI therapy after control of arrhythmia was achieved with antiarrhythmic drug therapy. CONCLUSIONS: Given the expanding long-term use of TKIs among a growing population of cancer patients, it is critical to acknowledge the association of TKIs with cardiovascular complications such as VAs, to characterize those at risk, and deploy preventive and therapeutic measures to avoid such complications and interference with oncologic therapy. Further efforts are warranted to develop monitoring protocols and optimal treatment strategies for TKI-induced VAs.

In-Hospital Mortality Rate and Predictors of 30-Day Readmission in Patients With Heart Failure Exacerbation and Atrial Fibrillation: A Cross-Sectional Study.

Background and Objectives: Heart failure (HF) and atrial fibrillation (AF) are considered new cardiovascular epidemics of the last decade. Recent national trends show an uptrend in HF hospitalizations. We aimed to identify the 30-day readmission rate, causes, and impact on healthcare utilization in HF exacerbation with a history of AF. Methods: We utilized 2018 Nationwide readmission data and included patients aged ≥18 years with International Classification of Diseases, Tenth Revision, Clinical Modification code indicating HF exacerbation and AF were included in the study. Primary outcome is 30-day readmission rates. Secondary outcomes were mortality rates, common causes of readmission, and healthcare utilization. Independent predictors for readmission were identified using cox regression analysis. Results: The total number of admissions in our study was 48,250. The mean age was 77.8 years (standard deviation, 12.1), and 47.74% were females. The 30-day readmission rate was 16.72%. The mortality rate at index admission and readmission was 7.28% and 8.12%, respectively. The most common cause of readmission was the hypertensive heart and kidney disease with HF. The independent predictors of readmission were low socio-economic class, Medicaid, Charlson comorbidities score. The financial burden on healthcare for all the readmission was $461 million for the year 2018. Conclusions: The 30-day readmission rate was 16.72%. The mortality rate increased from 7.28% to 8.12% with readmission. The financial burden for readmission during that year was $461 million. Future studies directed with interventions to prevents readmissions are warranted.

Busulfan and cyclophosphamide-based conditioning regimen still holds the promise of being a safe and efficacious regimen for allogeneic transplantation in patients with transfusion-dependent thalassemia, even in high risk.

Busulfan and cyclophosphamide (BuCy)-based regimen has been used as a standard myeloablative chemotherapy for haematopoietic stem cell transplantation in thalassemia. However, treosulfan-based conditioning regimen has emerged due to concerns of toxicities. We retrospectively analysed the safety and efficacy of fludrabine/Bu/Cy/antithymocyte globulin (ATG) versus treosulfan/thiotepa/fludrabine regimens for Hematopoietic Stem Cell Transplant (HSCT) in transfusion-dependent thalassemia (TDT) conducted at our institute (2013-2021). In 75 patients, 36 (48%) received Flu/Bu/Cy/ATG whereas 39 (52%) received Treo/Thio/Flu. Median age was 6 (1-12) and 9 (1-15) years, respectively. Number of patients with Classes I, II, and III were 14, 10, and 12 in Flu/Bu/Cy/ATG versus 2, 19, and 18 in Treo/Thio/Flu group, respectively. Graft was growth factor mobilized bone marrow in Flu/Bu/Cy/ATG versus peripheral blood stem cell in Treo/Thio/Flu group. Mean stem cell dose was 3.82 (2.2-9.1) versus 5 (1.65-8.01) 106 /kg in Flu/Bu/Cy/ATG versus Treo/Thio/Flu group, respectively. Neutrophils and platelets engrafted at a median of 16 (14-21) and 16 (9-47) days in Flu/Bu/Cy/ATG and 15 (10-20) and 13 (9-41) days in Treo/Thio/Flu group. Median duration of follow-up was 28 (23-32.9) months. Five (6.6%) patients had rejection (all secondary). Venoocclusive disease was observed in 2 (5.7%) versus 4 (10.3%) patients (p = .047), respectively. Flu/Bu/Cy/ATG had 4 (11.4%) patients with acute GVHD versus 15 (38.5%) patients which had significant impact on survival (p = .038). We observed chronic GVHD in 4 (11.4%) and 11 (28.2%) patients, respectively, with significant impact on survival (p = .031). Four (5.1%) patients had TRM in Treo/Thio/Flu group, in contrast to none in Flu/Bu/Cy/ATG group. Mixed chimerism was common in Flu/Bu/Cy/ATG {20 (57.1%)} versus Treo/Thio/Flu group {12 (30.1%)}. Five-year Event Free Survival (EFS) and OS of entire cohort were 87% + 4% and 94% + 3%, respectively. Estimated TFS, EFS, OS of Flu/Bu/Cy/ATG versus Treo/Thio/Flu was 97.1% + 2.9% versus 89.2% + 5.1% (p = .251), 97 + 3% versus 80.7 + 6% (p = .041) and 100% versus 90.4 + 5% (p = .067), respectively. In our experience, Flu/Bu/Cy/ATG regimen is safe and effective even in high-risk TDT. However, one needs to be vigilant for mixed chimerism.

Systematic Review and Network Meta-Analysis Comparing Bifurcation Techniques for Percutaneous Coronary Intervention.

Background Bifurcation lesions account for 20% of all percutaneous coronary interventions and represent a complex subset which are associated with lower procedural success and higher rates of restenosis. The ideal bifurcation technique, however, remains elusive. Methods and Results Extensive search of the literature was performed to pull data from randomized clinical trials that met predetermined inclusion criteria. Conventional meta-analysis produced pooled relative risk (RR) and 95% CI of 2-stent technique versus provisional stent on prespecified outcomes. Both frequentist and Bayesian network meta-analyses were performed to compare bifurcation techniques. A total of 8318 patients were included from 29 randomized clinical trials. Conventional meta-analysis showed no significant differences in all-cause mortality, cardiac death, major adverse cardiac events, myocardial infarction, stent thrombosis, target lesion revascularization, and target vessel revascularization between 2-stent techniques and provisional stenting. Frequentist network meta-analysis revealed that double kissing crush was associated with lower cardiac death (RR, 0.57; 95% CI, 0.38-0.84), major adverse cardiac events (RR, 0.50; 95% CI, 0.39-0.64), myocardial infarction (RR, 0.60; 95% CI, 0.39-0.90), stent thrombosis (RR, 0.50; 95% CI, 0.28-0.88), target lesion revascularization, and target vessel revascularization when compared with provisional stenting. Double kissing crush was also superior to other 2-stent techniques, including T-stent or T and protrusion, dedicated bifurcation stent, and culotte. Conclusions Double kissing crush was associated with lower risk of cardiac death, major adverse cardiac events, myocardial infarction, stent thrombosis, target lesion revascularization, and target vessel revascularization compared with provisional stenting and was superior to other 2-stent techniques. Superiority of 2-stent strategy over provisional stenting was observed in subgroup meta-analysis stratified to side branch lesion length ≥10 mm.

The analgesic efficacy of intravenous dexamethasone for post-caesarean pain: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Analgesic efficacy of intravenous dexamethasone has not been well defined after caesarean delivery. We performed a systematic review and meta-analysis to evaluate the impact of peri-operative dexamethasone administration on postoperative pain after caesarean delivery. OBJECTIVES: We investigated the impact of perioperative intravenous dexamethasone on postoperative pain after caesarean delivery. The two primary outcomes of interest were early (4 to 6 h) resting pain scores and time to first rescue analgesia. DESIGN: A systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: PubMed, EMBASE, Scopus and the Cochrane central registers of controlled trials were searched to identify RCTs from inception to April 2021. ELIGIBILITY CRITERIA: Prospective RCTs comparing the role of intravenous dexamethasone with non-active control were eligible for inclusion. Exclusion criteria included trials comparing various doses of dexamethasone without any control treatment arm, dexamethasone with other active drugs and trials comparing different routes of dexamethasone, for example, wound infiltration. RESULTS: Thirteen RCTs constituting of 988 parturients undergoing caesarean delivery were included. Patients receiving dexamethasone had lower pain scores at rest at 4 to 6 h after surgery, mean difference -1.29 [95% confidence interval (CI), -1.85 to -0.73], P < 0.0001, with low quality of evidence (I2 = 94%). Moderate quality of evidence (I2 = 17%) suggested that the time to first rescue analgesia in the dexamethasone group was significantly longer, mean difference 2.64 h (95% CI, 1.85 to 3.42), P  < 0.0001. Trial sequential analysis for pain scores suggested the benefit of dexamethasone; however, the requisite information size (RIS) could not be reached, whereas RIS was adequate for time to rescue analgesia. Significant reduction in pain scores at all times and opioid consumption at 24 h with dexamethasone were observed with sparse reporting on adverse effects. CONCLUSION: Peri-operative intravenous dexamethasone was associated with a significant decrease in postoperative pain scores at rest and a longer time to first rescue analgesia, along with a small but statistically significantly reduced opioid consumption after caesarean delivery compared with nonactive control.

Radiological criteria for disconnected pancreatic duct syndrome: a targeted literature review.

INTRODUCTION: In patients with acute necrotizing pancreatitis (ANP), parenchymal necrosis may involve the pancreatic duct, isolating a segment of the pancreas that remains functional but drains its secretions into the peripancreatic fluid collections, leading to disconnected pancreatic duct syndrome (DPDS). DPDS is an important complication of ANP associated with long-term morbidity and mortality. Unfortunately, this critical entity is under-recognized by radiologists. Endoscopic retrograde cholangiopancreatography (ERCP) is considered the gold standard for diagnosing and treating such patients. However, considering the invasiveness of the ERCP, a noninvasive diagnosis based on radiological tests is desirable. Radiological literature concerning the diagnosis of DPDS is scarce, and there is substantial ambiguity regarding the radiological definitions of DPDS. AREAS COVERED: Considering the scarcity of published literature regarding the reliable radiologic diagnosis of DPDS, we performed a thorough review of the existing literature to identify definitions and features of this entity on computed tomography (CT) and magnetic resonance imaging (MRI). EXPERT OPINION: Existing literature regarding radiologic diagnosis of DPDS was reviewed and analyzed and a comprehensive imaging definition of DPDS was proposed.