Frequency of etiologies of acute kidney injury in Faisalabad and surrounding districts

Background: To find out the causes of Acute Kidney Injury (AKI) in population.Methods: A total of 150 patients were enrolled from medical, surgical, gynecology and obstetrics units of Allied Hospital and Madinah Teaching Hospital, Faisalabad, Pakistan. History, physical examination and investigations were recorded on specially designed proforma. Patients were evaluated to find out the etiologies of AKI. All patients were subjected to urine analysis, complete blood count, blood biochemistry (urea, creatinine, electrolytes, uric acid, calcium and phosphorus) and ultrasound scan of the abdomen and pelvis. Renal biopsy, immunological assays, such as hepatitis B surface antigen, anti-hepatitis C virus antibody, complements level, antinuclear antibody, anti-double-stranded DNA, anti-neutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody were performed in selected cases.Results: Male (36%) and female (64%). Pre-renal AKI was most common and was reported in 80 patients (53.33%). Intrinsic Renal azotemia in 56 patients (37.33%). Post renal azotemia in 14 patients (9.33%). Among 80 patients of prerenal AKI, hemorrhage in 45(56.25%), gastroenteritis in 16(20%), sepsis in 8(10%), cardiac diseases in 4(5%), hepatorenal syndrome in 3 (3.75%), peritonitis in 2 (2.50%) and burns in 2(2.50%) were the main causes of Pre-renal AKI. Among 56 patients of intrinsic renal AKI, 40(71.4%) had acute tubular necrosis (ATN), 12(21.4%) with multifactorial causes and 4(7.14%) were found to have glomerulonephritis. Among 14 patients of post renal AKI, 6(42.9%) were having calculi, 6(42.9%) were to have enlarged prostate and 2(4.3%) were having stricture urethra. In this study, contribution of obstetrical, medical and surgical etiologies were recorded as 40%, 36% and 20% respectively.Conclusions: In contrast to study reported from neighbouring country, this study shows rather increase in pregnancy related AKI

Removal of Transition-Metal Ions by Metal-Complexing Polythiosemicarbazone Membranes

Membrane technology is one of the many strategies to remove transition-metal ions from aqueous streams because of its relatively lower costs and ease of operation. Typically, adsorbent materials are added into polymeric membranes to impart chelating/complexing properties, but this often results in a limited number of adsorption sites within the membrane. In this work, polythiosemicarbazone (pTSC) is proposed as a material to prepare polymeric membranes due to its metal-complexing ligands in the backbone, providing more adsorption sites. The polymer was easily processed into membranes via the nonsolvent-induced phase separation technique and exhibited asymmetric structures with adequate mechanical strength. The porosity of the membranes was controlled by increasing the polymer concentration in the casting solution, leading to ultrafiltration- and nanofiltration-type membranes with permeabilities ranging from 30 to 0.7 L·m$^{–2}$·h$^{–1}$·bar$^{–1}$. The resulting pTSC membranes were applied for the removal of silver and copper ions in batch and, in the case of silver ions, also in dynamic adsorption experiments. The maximum removal rate of 17 mg·g$^{–1}$ for silver and 3.8 mg·g$^{–1}$ for copper ions was obtained in the batch removal experiment. Streaming potential, pH measurements, and infrared spectroscopy (FTIR) were conducted to verify the anionic binding of TSC groups, while neutral binding modes were revealed by FTIR and batch removal experiments. Furthermore, the removal of silver ions was also successfully demonstrated in a flow setup operated at 4 bar of applied pressure. The streaming potential and energy-dispersive X-ray (EDX) spectroscopy conducted on the membranes after the flow tests confirmed the complexation by TSC-functional groups as the separation mechanism. Finally, partial desorption of the silver ions was successfully conducted in water to demonstrate the reusability of pTSC membranes

Prevalence of Muscle Dysmorphia and Associated Health Activities in Male Medical Students in Karachi, Pakistan

Background: Muscle Dysmorphia (MD) is a subtype of body dysmorphic disorder (BDD) and is currently classified under anxiety disorders (subheading: Obsessive-compulsive disorder) in DSM 5. MD is hypothesized to affect the self-esteem and social outlook of the younger generation. MD shows a higher rate in males and may influence their self-confidence rendering them more prone towards using steroids, supplementary proteins and other drugs to alter their physical outlooks as shown in previous studies. This problem has been on the rise lately due to revolutionary advancement in the media and film industry and the abrupt changes about the standards of physical good looks and body shapes. With the lack of studies done in our population, our study will be helpful to consider the prevalence of the disease in our setting and increase awareness in the general public and clinicians. We hope to help clinicians/ therapists find better options in managing the disease. Materials: We performed a cross-sectional study with a sample size of 246 medical school students in Karachi to collect data through self-administered questionnaires. We used the DSM 5 criteria for the diagnosis of BDD and additional questions on the presence of MD. Nutritional habits, exercise routines, use of supplements and drugs were also obtained for exploratory analysis. Results: Our study predicted the prevalence of MD to be 25%. Other main findings included statistical significant associations between MD and the thoughts and practice of steroid use for muscularity. Conclusion: MD is an underdiagnosed and often unrecognized disease that we believe has significant consequences for the young male population. Further work is needed on this in our part of the world. Our research, we believe, can be a stepping stone for further studies that would incorporate wider populations

Home‐Based Cardiac Rehabilitation Alone and Hybrid With Center‐Based Cardiac Rehabilitation in Heart Failure: A Systematic Review and Meta‐Analysis

Background Center‐based cardiac rehabilitation (CBCR) has been shown to improve outcomes in patients with heart failure (HF). Home‐based cardiac rehabilitation (HBCR) can be an alternative to increase access for patients who cannot participate in CBCR. Hybrid cardiac rehabilitation (CR) combines short‐term CBCR with HBCR, potentially allowing both flexibility and rigor. However, recent data comparing these initiatives have not been synthesized. Methods and Results We performed a meta‐analysis to compare functional capacity and health‐related quality of life (hr‐QOL) outcomes in HF for (1) HBCR and usual care, (2) hybrid CR and usual care, and (3) HBCR and CBCR. A systematic search in 5 standard databases for randomized controlled trials was performed through January 31, 2019. Summary estimates were pooled using fixed‐ or random‐effects (when I2\u3e50%) meta‐analyses. Standardized mean differences (95% CI) were used for distinct hr‐QOL tools. We identified 31 randomized controlled trials with a total of 1791 HF participants. Among 18 studies that compared HBCR and usual care, participants in HBCR had improvement of peak oxygen uptake (2.39 mL/kg per minute; 95% CI, 0.28–4.49) and hr‐QOL (16 studies; standardized mean difference: 0.38; 95% CI, 0.19–0.57). Nine RCTs that compared hybrid CR with usual care showed that hybrid CR had greater improvements in peak oxygen uptake (9.72 mL/kg per minute; 95% CI, 5.12–14.33) but not in hr‐QOL (2 studies; standardized mean difference: 0.67; 95% CI, −0.20 to 1.54). Five studies comparing HBCR with CBCR showed similar improvements in functional capacity (0.0 mL/kg per minute; 95% CI, −1.93 to 1.92) and hr‐QOL (4 studies; standardized mean difference: 0.11; 95% CI, −0.12 to 0.34). Conclusions HBCR and hybrid CR significantly improved functional capacity, but only HBCR improved hr‐QOL over usual care. However, both are potential alternatives for patients who are not suitable for CBCR

Microduplications encompassing the Sonic hedgehog limb enhancer ZRS are associated with Haas-type polysyndactyly and Laurin-Sandrow syndrome

Laurin-Sandrow syndrome (LSS) is a rare autosomal dominant disorder characterized by polysyndactyly of hands and/or feet, mirror image duplication of the feet, nasal defects, and loss of identity between fibula and tibia. The genetic basis of LSS is currently unknown. LSS shows phenotypic overlap with Haas-type polysyndactyly (HTS) regarding the digital phenotype. Here we report on five unrelated families with overlapping microduplications encompassing the Sonic hedgehog (SHH) limb enhancer ZPA regulatory sequence (ZRS) on chromosome 7q36. Clinically, the patients show polysyndactyly phenotypes and various types of lower limb malformations ranging from syndactyly to mirror image polydactyly with duplications of the fibulae. We show that larger duplications of the ZRS region (>80 kb) are associated with HTS, whereas smaller duplications (<80 kb) result in the LSS phenotype. On the basis of our data, the latter can be clearly distinguished from HTS by the presence of mirror image polysyndactyly of the feet with duplication of the fibula. Our results expand the clinical phenotype of the ZRS-associated syndromes and suggest that smaller duplications (<80 kb) are associated with a more severe phenotype. In addition, we show that these small microduplications within the ZRS region are the underlying genetic cause of Laurin-Sandrow syndrome

A missense mutation in the PISA domain of HsSAS-6 causes autosomal recessive primary microcephaly in a large consanguineous Pakistani family

Asymmetric cell division is essential for normal human brain development. Mutations in several genes encoding centrosomal proteins that participate in accurate cell division have been reported to cause autosomal recessive primary microcephaly (MCPH). By homozygosity mapping including three affected individuals from a consanguineous MCPH family from Pakistan, we delineated a critical region of 18.53 Mb on Chromosome 1p21.3-1p13.1. This region contains the gene encoding HsSAS-6, a centrosomal protein primordial for seeding the formation of new centrioles during the cell cycle. Both next-generation and Sanger sequencing revealed a homozygous c.185T>C missense mutation in the HsSAS-6 gene, resulting in a p.Ile62Thr substitution within a highly conserved region of the PISA domain of HsSAS-6. This variant is neither present in any single-nucleotide polymorphism or exome sequencing databases nor in a Pakistani control cohort. Experiments in tissue culture cells revealed that the Ile62Thr mutant of HsSAS-6 is substantially less efficient than the wild-type protein in sustaining centriole formation. Together, our findings demonstrate a dramatic impact of the mutation p.Ile62Thr on HsSAS-6 function and add this component to the list of genes mutated in primary microcephal

A randomized controlled trial of metformin on left ventricular hypertrophy in patients with coronary artery disease without diabetes:the MET-REMODEL trial

Aim We tested the hypothesis that metformin may regress left ventricular hypertrophy (LVH) in patients who have coronary artery disease (CAD), with insulin resistance (IR) and/or pre-diabetes. Methods and results We randomly assigned 68 patients (mean age 65 ± 8 years) without diabetes who have CAD with IR and/or pre-diabetes to receive either metformin XL (2000 mg daily dose) or placebo for 12 months. Primary endpoint was change in left ventricular mass indexed to height1.7 (LVMI), assessed by magnetic resonance imaging. In the modified intention-to-treat analysis (n = 63), metformin treatment significantly reduced LVMI compared with placebo group (absolute mean difference −1.37 (95% confidence interval: −2.63 to −0.12, P = 0.033). Metformin also significantly reduced other secondary study endpoints such as: LVM (P = 0.032), body weight (P = 0.001), subcutaneous adipose tissue (P = 0.024), office systolic blood pressure (BP, P = 0.022) and concentration of thiobarbituric acid reactive substances, a biomarker for oxidative stress (P = 0.04). The glycated haemoglobin A1C concentration and fasting IR index did not differ between study groups at the end of the study. Conclusion Metformin treatment significantly reduced LVMI, LVM, office systolic BP, body weight, and oxidative stress. Although LVH is a good surrogate marker of cardiovascular (CV) outcome, conclusive evidence for the cardio-protective role of metformin is required from large CV outcomes trials

Global, regional, and national burden of rheumatoid arthritis, 1990–2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021

Background Rheumatoid arthritis is a chronic autoimmune inflammatory disease associated with disability and premature death. Up-to-date estimates of the burden of rheumatoid arthritis are required for health-care planning, resource allocation, and prevention. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, we provide updated estimates of the prevalence of rheumatoid arthritis and its associated deaths and disability-adjusted life-years (DALYs) by age, sex, year, and location, with forecasted prevalence to 2050. Methods Rheumatoid arthritis prevalence was estimated in 204 countries and territories from 1990 to 2020 using Bayesian meta-regression models and data from population-based studies and medical claims data (98 prevalence and 25 incidence studies). Mortality was estimated from vital registration data with the Cause of Death Ensemble model (CODEm). Years of life lost (YLL) were calculated with use of standard GBD lifetables, and years lived with disability (YLDs) were estimated from prevalence, a meta-analysed distribution of rheumatoid arthritis severity, and disability weights. DALYs were calculated by summing YLLs and YLDs. Smoking was the only risk factor analysed. Rheumatoid arthritis prevalence was forecast to 2050 by logistic regression with Socio-Demographic Index as a predictor, then multiplying by projected population estimates. Findings In 2020, an estimated 17·6 million (95% uncertainty interval 15·8–20·3) people had rheumatoid arthritis worldwide. The age-standardised global prevalence rate was 208·8 cases (186·8–241·1) per 100 000 population, representing a 14·1% (12·7–15·4) increase since 1990. Prevalence was higher in females (age-standardised female-to-male prevalence ratio 2·45 [2·40–2·47]). The age-standardised death rate was 0·47 (0·41–0·54) per 100 000 population (38 300 global deaths [33 500–44 000]), a 23·8% (17·5–29·3) decrease from 1990 to 2020. The 2020 DALY count was 3 060 000 (2 320 000–3 860 000), with an age-standardised DALY rate of 36·4 (27·6–45·9) per 100 000 population. YLDs accounted for 76·4% (68·3–81·0) of DALYs. Smoking risk attribution for rheumatoid arthritis DALYs was 7·1% (3·6–10·3). We forecast that 31·7 million (25·8–39·0) individuals will be living with rheumatoid arthritis worldwide by 2050. Interpretation Rheumatoid arthritis mortality has decreased globally over the past three decades. Global age-standardised prevalence rate and YLDs have increased over the same period, and the number of cases is projected to continue to increase to the year 2050. Improved access to early diagnosis and treatment of rheumatoid arthritis globally is required to reduce the future burden of the disease.publishedVersio

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p &lt; 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p &lt; 0.001) and 1.99 (95%CI 1.34-2.99, p &lt; 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p &lt; 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure