Enhanced mucosal mitochondrial function corrects dysbiosis and OXPHOS metabolism in IBD.

Background: Mitochondrial (Mito) dysfunction in IBD reduces mucosal O2 consumption and increases O2 delivery to the microbiome. Increased enteric O2 promotes blooms of facultative anaerobes (eg. Proteobacteria ) and restricts obligate anaerobes (eg. Firmicutes ). Dysbiotic metabolites negatively affect host metabolism and immunity. Our novel compound (AuPhos) upregulates intestinal epithelial cell (IEC) mito function, attenuates colitis and corrects dysbiosis in humanized Il10-/- mice. We posit that AuPhos corrects IBD-associated dysbiotic metabolism. Methods: Primary effect of AuPhos on mucosal Mito respiration and healing process was studied in ex vivo treated human colonic biopsies and piroxicam-accelerated (Px) Il10-/- mice. Secondary effect on microbiome was tested in DSS-colitis WT B6 and germ-free 129.SvEv WT or Il10-/- mice reconstituted with human IBD stool (Hu- Il10-/- ). Mice were treated orally with AuPhos (10- or 25- mg/kg; q3d) or vehicle, stool samples collected for fecal lipocalin-2 (f-LCN2) assay and microbiome analyses using 16S rRNA sequencing. AuPhos effect on microbial metabolites was determined using untargeted global metabolomics. AuPhos-induced hypoxia in IECs was assessed by Hypoxyprobe-1 staining in sections from pimonidazole HCl-infused DSS-mice. Effect of AuPhos on enteric oxygenation was assessed by E. coli Nissle 1917 WT (aerobic respiration-proficient) and cytochrome oxidase (cydA) mutant (aerobic respiration-deficient). Results: Metagenomic (16S) analysis revealed AuPhos reduced relative abundances of Proteobacteria and increased blooms of Firmicutes in uninflamed B6 WT, DSS-colitis, Hu-WT and Hu- Il10-/- mice. AuPhos also increased hypoxyprobe-1 staining in surface IECs suggesting enhanced O2 utilization. AuPhos-induced anaerobiosis was confirmed by a significant increase in cydA mutant compared to WT (O2-utlizing) E.coli . Ex vivo treatment of human biopsies with AuPhos showed significant increase in Mito mass, and complexes I and IV. Further, gene expression analysis of AuPhos-treated biopsies showed increase in stem cell markers (Lgr4, Lgr5, Lrig1), with concomitant decreases in pro-inflammatory markers (IL1ß,MCP1, RankL). Histological investigation of AuPhos-fed Px- Il10-/- mice showed significantly decreased colitis score in AuPhos-treated Px- Il10-/- mice, with decrease in mRNA of pro-inflammatory cytokines and increase in Mito complexes ( ND5 , ATP6 ). AuPhos significantly altered microbial metabolites associated with SCFA synthesis, FAO, TCA cycle, tryptophan and polyamine biosynthesis pathways. AuPhos increased pyruvate, 4-hydroxybutyrate, 2-hydroxyglutarate and succinate, suggesting an upregulation of pyruvate and glutarate pathways of butyrate production. AuPhos reduced IBD-associated primary bile acids (BA) with concomitant increase in secondary BA (SBA). AuPhos treatment significantly decreased acylcarnitines and increased L-carnitine reflective of enhanced FAO. AuPhos increases TCA cycle intermediates and creatine, energy reservoir substrates indicating enhanced OxPHOS. Besides, AuPhos also upregulates tryptophan metabolism, decreases Kynurenine and its derivatives, and increases polyamine biosynthesis pathway (Putresceine and Spermine). Conclusion: These findings indicate that AuPhos-enhanced IEC mitochondrial function reduces enteric O2 delivery, which corrects disease-associated metabolomics by restoring short-chain fatty acids, SBA, AA and IEC energy metabolism.

Disease clearance in ulcerative colitis: A new therapeutic target for the future.

Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression. This has fueled the identification of molecular targets, resulting in a rapidly expanding therapeutic armamentarium. Subsequently, management strategies have evolved from symptomatic resolution to well-defined objective endpoints, including clinical remission, endoscopic remission and mucosal healing. While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications, studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures. Current recommendations lack consideration of histological healing. The simultaneous achievement of clinical, endoscopic, and histologic remission has not been fully investigated. This has laid the groundwork for a novel therapeutic outcome termed disease clearance (DC). This article summarizes the concept of DC and its current evidence.

Effectiveness of Upadacitinib for Patients With Acute Severe Ulcerative Colitis: A Multicenter Experience.

INTRODUCTION: A significant proportion of patients with acute severe ulcerative colitis (ASUC) require colectomy. METHODS: Patients with ASUC treated with upadacitinib and intravenous corticosteroids at 5 hospitals are presented. The primary outcome was 90-day colectomy rate. Secondary outcomes included frequency of steroid-free clinical remission, adverse events, and all-cause readmissions. RESULTS: Of the 25 patients with ASUC treated with upadacitinib, 6 (24%) patients underwent colectomy, 15 (83%) of the 18 patients with available data and who did not undergo colectomy experienced steroid-free clinical remission (1 patient did not have complete data), 1 (4%) patient experienced a venous thromboembolic event, while 5 (20%) patients were readmitted. DISCUSSION: Upadacitinib along with intravenous corticosteroids may be an effective treatment for ASUC.

Electrical neuromodulation therapy for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an inflammatory disease of the gastrointestinal (GI) tract. It has financial and quality of life impact on patients. Although there has been a significant advancement in treatments, a considerable number of patients do not respond to it or have severe side effects. Therapeutic approaches such as electrical neuromodulation are being investigated to provide alternate options. Although bioelectric neuromodulation technology has evolved significantly in the last decade, sacral nerve stimulation (SNS) for fecal incontinence remains the only neuromodulation protocol commonly utilized use for GI disease. For IBD treatment, several electrical neuromodulation techniques have been studied, such as vagus NS, SNS, and tibial NS. Several animal and clinical experiments were conducted to study the effectiveness, with encouraging results. The precise underlying mechanisms of action for electrical neuromodulation are unclear, but this modality appears to be promising. Randomized control trials are required to investigate the efficacy of intrinsic processes. In this review, we will discuss the electrical modulation therapy for the IBD and the data pertaining to it.

Efficacy and Safety of Catheter Ablation vs Antiarrhythmic Drugs as Initial Therapy for Management of Symptomatic Paroxysmal Atrial Fibrillation: A Meta-Analysis.

BACKGROUND: Catheter ablation is an effective treatment for atrial fibrillation (AF), primarily performed in patients who fail antiarrhythmic drugs. Whether early catheter ablation, as first-line therapy, is associated with improved clinical outcomes remains unclear. METHODS: Electronic databases (PubMed, Scopus, Embase) were searched until March 28th, 2021. Randomized controlled trials (RCTs) compared catheter ablation vs antiarrhythmic drug therapy as first-line therapy were included. The primary outcome of interest was the first documented recurrence of any atrial tachyarrhythmia (symptomatic or asymptomatic; AF, atrial flutter, and atrial tachycardia). Secondary outcomes included symptomatic atrial tachyarrhythmia (AF, atrial flutter, and atrial tachycardia) and serious adverse events. Unadjusted risk ratios (RR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance considered if the confidence interval (CI) excludes one and p < 0.05. RESULTS: A total of six RCTs with 1212 patients (Ablation n = 609; Antiarrhythmic n = 603) were included. Follow- up period ranged from 1-2 years. Patients who underwent ablation were less likely to experience any recurrent atrial tachyarrhythmia when compared to patients receiving antiarrhythmic drugs (RR 0.63; 95% CI 0.55-0.73; p < 0.00001). Symptomatic atrial tachyarrhythmia was also lower in the ablation arm (RR 0.53; 95% CI 0.32-0.87; p = 0.01). No statistically significant differences were noted for overall any type of adverse events (RR 0.93; 95% CI 0.68-1.27; p = 0.64) and cardiovascular adverse events (RR 0.90; 95% CI 0.56-1.44; p = 0.65) respectively. CONCLUSIONS: Catheter ablation, as first-line therapy, was associated with a significantly lower rate of tachyarrhythmia recurrence compared to conventional antiarrhythmic drugs, with a similar adverse effect risk profile. These findings support a catheter ablation strategy as first-line therapy among patients with symptomatic paroxysmal atrial fibrillation.

Artificial intelligence in the diagnosis and detection of heart failure: the past, present, and future.

Artificial Intelligence (AI) performs human intelligence-dependant tasks using tools such as Machine Learning, and its subtype Deep Learning. AI has incorporated itself in the field of cardiovascular medicine, and increasingly employed to revolutionize diagnosis, treatment, risk prediction, clinical care, and drug discovery. Heart failure has a high prevalence, and mortality rate following hospitalization being 10.4% at 30-days, 22% at 1-year, and 42.3% at 5-years. Early detection of heart failure is of vital importance in shaping the medical, and surgical interventions specific to HF patients. This has been accomplished with the advent of Neural Network (NN) model, the accuracy of which has proven to be 85%. AI can be of tremendous help in analyzing raw image data from cardiac imaging techniques (such as echocardiography, computed tomography, cardiac MRI amongst others) and electrocardiogram recordings through incorporation of an algorithm. The use of decision trees by Rough Sets (RS), and logistic regression (LR) methods utilized to construct decision-making model to diagnose congestive heart failure, and role of AI in early detection of future mortality and destabilization episodes has played a vital role in optimizing cardiovascular disease outcomes. The review highlights the major achievements of AI in recent years that has radically changed nearly all areas of HF prevention, diagnosis, and management.

Associated Factors With Uremic Pruritus in Chronic Hemodialysis Patients: A Single-Center Observational Study.

Background and objectives Uremic pruritus is a recurrent and delicate manifestation in patients suffering from end-stage renal disease. It is a consequence of multiple factors, primarily comprising of metabolic factors and complement activation along with interleukins. The objective of our study was to find out the associated factors of uremic pruritus in chronic hemodialysis patients. The secondary aim was to obtain cut-off values of all the markers predicting pruritus. Materials and methods A cross-sectional observational study was conducted in the nephrology department of a tertiary care hospital including 135 patients. The current occurrence of pruritus was diagnosed on the basis of a validated and reliable scale of pruritus among chronic kidney disease (CKD) patients in the local language. Multivariate logistic regression and receiver operating characteristic analysis were conducted to decipher the required objectives. Results Study participants had a mean age of 56.29 ± 10.51 years with 56.3% males and 43.7% females. Hypertension was frequent comorbidity (75.6%) followed by diabetes (51.9%). Mean body mass index (BMI), duration of CKD diagnosis, and hemodialysis onset were 26.55 ± 5.37 kg/m2, 6.58 ± 3.65 years, and 3.32 ± 2.09 years respectively. Pruritus was reported in 37.0% of the study participants. On multivariate logistic regression, presence of skin allergy (aOR: 8.100 [2.926-22.420], p<0.001), phosphate >4.5 mg/dL (aOR: 3.889 [1.118-15.532], p=0.033), female gender (aOR: 3.592 [1.337-9.655], p=0.011), albumin <3.5 g/dL (aOR: 2.987 [1.156-7.716], p=0.024) and potassium >5.1 mEq/L (aOR: 2.934 [1.030-8.355], p=0.044) were found significantly associated with pruritus. Conclusion Many factors were linked to pruritus in hemodialysis patients in the current study. The current study also significantly correlated certain factors with pruritus independently.

A Meta-Analysis of Association between Remdesivir and Mortality among Critically-Ill COVID-19 Patients.

BACKGROUND: The World Health Organization guidelines did not make a recommendation on use of remdesivir based on disease severity. Little is known regarding effectiveness of remdesivir in critically ill coronavirus disease 2019 (COVID-19) patients. This has led to a state of dilemma for doctors leaving them skeptical of whether they should continue to recommend the drug or not. MATERIALS AND METHODS: A systematic search adhering to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines was conducted from inception until February 20, 2020. Electronic bibliographic databases (PubMed, Cochrane database, Scopus, Embase) were included. Using dichotomous data for select values, the unadjusted odds ratios (ORs) were calculated applying Mantel Haenszel (M-H) using random-effects model. The primary outcome of interest was all-cause mortality in ventilated and non-ventilated patients. RESULTS: The Remdesivir arm was associated with similar rates of 28-day all-cause mortality (OR: 0.93, 95% confidence interval [CI]: 0.80 - 1.08; P = 0.33). Remdesivir was not found to be favorable for ventilated patients. Non ventilated COVID-19 patients showed a significant lower in-hospital mortality rate as compared with patients requiring mechanical ventilatory support (OR: 6.86, 95% CI: 5.39 - 268.74; P <0.0001). CONCLUSION: Non-ventilated patients were associated with significant lower all-cause mortality rates. Prudent use of remdesivir is recommended in critically ill COVID-19 patients.

Clinical Presentations and Outcomes of Coronavirus Disease 2019 in Patients With Solid Tumors.

Background Coronavirus disease 2019 (COVID-19) is a global health crisis. The literature suggests that cancer patients are more prone to be affected by COVID-19 because cancer suppresses the immune system and such patients usually present poor results. The objective of this study is to present all clinical, laboratory, and demographic characteristics of COVID-19 patients with solid tumors. Methodology This study was conducted at the Dow University of Health Sciences for a period of six months from April 2020 to September 2020. In this study, we included a total of 1,519 confirmed patients diagnosed with solid tumors via polymerase chain reaction. The mortality timeline within 30 days of contracting the virus was considered, and the median age of the included individuals was 61 years, with a range of 20-95 years. Of the patients included in the study, 49.4% (750) were men; moreover, 3.15% of our study population had prostate cancer, 10.20% had colorectal cancer, 2.76% had breast cancer, and 10.46% had lung cancer. Of the patients, 25.93% presented with at least one comorbidity. For 73% of the patients, at least one direct therapy for COVID-19 was included in the treatment; 56.6% of the patients were hospitalized, and 11.32% were admitted to the intensive care unit. Results The mortality rate was 4.74% in the first 30 days after diagnosis, where 72 patients died. The findings of the first multi-variation model showed that males at older ages who were diabetic and going through cytotoxic therapy were prone to die within the first 30 days. However, the 30-day mortality rate was lower in patients diagnosed with prostate and breast cancer. The second set incorporated laboratory factors, where we found that higher values of leukocytosis, thrombocytopenia, and lymphocytopenia were correlated with higher rates of mortality within 30 days. Conclusions We conclude that there is a higher mortality rate of COVID-19 in patients with solid tumors than in the general population. However, it was found to be lower in the Pakistani population compared with the Chinese and Western populations. Intensive care can decrease mortality rates in COVID-19 and cancer patients.

Comparison of Repeated Doses of C-kit-Positive Cardiac Cells versus a Single Equivalent Combined Dose in a Murine Model of Chronic Ischemic Cardiomyopathy.

Using a murine model of chronic ischemic cardiomyopathy caused by an old myocardial infarction (MI), we have previously found that three doses of 1 × 106 c-kit positive cardiac cells (CPCs) are more effective than a single dose of 1 × 106 cells. The goal of this study was to determine whether the beneficial effects of three doses of CPCs (1 × 106 cells each) can be fully replicated by a single combined dose of 3 × 106 CPCs. Mice underwent a 60-min coronary occlusion; after 90 days of reperfusion, they received three echo-guided intraventricular infusions at 5-week intervals: (1) vehicle × 3; (2) one combined dose of CPCs (3 × 106) and vehicle × 2; or (3) three doses of CPCs (1 × 106 each). In the combined-dose group, left ventricular ejection fraction (LVEF) improved after the 1st CPC infusion, but not after the 2nd and 3rd (vehicle) infusions. In contrast, in the multiple-dose group, LVEF increased after each CPC infusion; at the final echo, LVEF averaged 35.2 ± 0.6% (p < 0.001 vs. the vehicle group, 27.3 ± 0.2%). At the end of the study, the total cumulative change in EF from pretreatment values was numerically greater in the multiple-dose group (6.6 ± 0.6%) than in the combined-dose group (4.8 ± 0.8%), although the difference was not statistically significant (p = 0.08). Hemodynamic studies showed that several parameters of LV function in the multiple-dose group were numerically greater than in the combined-dose group (p = 0.08 for the difference in LVEF). Compared with vehicle, cardiomyocyte cross-sectional area was reduced only in the multiple-dose group (-32.7%, 182.6 ± 15.1 µm2 vs. 271.5 ± 27.2 µm2, p < 0.05, in the risk region and -28.5%, 148.5 ± 12.1 µm2 vs. 207.6 ± 20.5 µm2, p < 0.05, in the noninfarcted region). LV weight/body weight ratio and LV weight/tibia length ratios were significantly reduced in both cell treated groups vs. the vehicle group, indicating the attenuation of LV hypertrophy; however, the lung weight/body weight ratio was significantly reduced only in the multiple-dose group, suggesting decreased pulmonary congestion. Taken together, these results indicate that in mice with chronic ischemic cardiomyopathy, the beneficial effects of three doses of CPCs on LV function and hypertrophy cannot be fully replicated with a single dose, notwithstanding the fact that the total number of cells delivered with one or three doses is the same. Thus, it is the multiplicity of doses, and not the total number of cells, that accounts for the superiority of the repeated-dose paradigm. This study supports the idea that the efficacy of cell therapy in heart failure can be augmented by repeated administrations.

Functional Outcomes of Cementless Total Hip Arthroplasty in Avascular Necrosis of the Hip: A Prospective Study.

Introduction Avascular necrosis occurs due to impaired blood supply to the bone. It can be caused by fractures, dislocations, chronic steroid use, chronic alcohol use, coagulopathy, congenital source, and many other factors. It mostly affects the femoral head (hip joint). Its management can be conservative or invasive. Total hip arthroplasty is the treatment of choice for third and fourth stage avascular necrosis that can be cemented or uncemented. The purpose of this study is to access the functional outcomes of cementless total hip arthroplasty in patients with avascular necrosis of the hip. Materials and methods This prospective study was conducted at a major metropolitan hospital in Karachi, Pakistan over a period of six months. A total of 30 patients of age <60 years, either gender, and a confirmed diagnosis of avascular necrosis of hip with no other associated hip pathologies were included in this study. Demographic features, comorbidities, level of activity, range of movement before the development of avascular necrosis, Charnley's class, and laterality were noted. Cementless press-fit extensively porous-coated acetabular cup with or without cancellous screws and cementless press-fit extensively hydroxyapatite coated femoral stem were used through modified Gibson's posterior approach. The patients were checked for early and late complications, the position of acetabular and femoral components by radiography, and overall performance by Harris Hip Score (HHS) and modified HHS over a period of 12 months. All statistical analyses were performed using Statistical Package for Social Sciences (SPSS) version 19.0 (IBM Corp, Armonk, NY). Results The mean age was 43.9±6.7 years with 21 (70%) patients ranging from 40 to 60 years of age. There were 22 (73%) male and 8 (27%) female patients. Nine (30%) patients had diabetes mellitus, eight (27%) had hypertension, two (7%) had other comorbidities, and eleven (37%) had no comorbidities. A total of 11 (37%) patients were highly active, 18 (60%) were moderately active, and 1 (3%) was non-active before developing avascular necrosis. There were 4 (13%) patients in Charnley's class I, 15 (50%) in Charnley's class II, and 11 (37%) in Charnley's class III. Fifteen (50%) patients were operated on the left side, seven (23%) on the right side, and eight (27%) bilaterally. No significant early or late complications were noted. Acetabular component was found to be anteverted in 22 (73%), retroverted in zero (0%), neutral in 8 (27%), <35o inclined in 0 (0%), 35o-50o inclined in 23 (77%), and >50o inclined in 7 (23%) patients, while femoral component was found neutral in 28 (93%), valgus in 2 (7%), and varus in zero (0%) patients on radiography at follow-up. On functional assessment, the HHS was 100% in 27 (90%) patients, 96% in 2 (7%) patients, and 83% in 1 (3%) patient with an average of 99.2%, while 29 (97%) patients had excellent and only 1 (3%) patient had a good outcome on modified HHS. Conclusions Cementless total hip arthroplasty, performed in patients <60 years of age and avascular necrosis of the hip with no other associated hip pathologies, has excellent functional outcomes with no pain, limping, physical deformity, difficulty in walking, difficulty in climbing stairs, difficulty using public transport, difficulty in sitting, or difficulty in wearing shoes and socks. They usually attain normal limb length and range of movement.

Symptomatic Cavum Septum Pellucidum Cyst: A Rare Presentation.

A cavum septum pellucidum is a cerebrospinal fluid (CSF) filled cavity situated between the lateral ventricles and is considered as a normal anatomic variant sporadically seen on neuroimaging. While a cavum septum pellucidum is a relatively uncommon incidental neuroimaging finding, symptomatic cysts of the cavum septum pellucidum are very rare, with only a few cases reported in the literature so far. They are defined as fluid-filled structures with lateral bowing of the walls and membranes separated by at least 10 mm or more. We present the case of a 25-year-old male patient with a rapidly expanding cyst of the septum pellucidum with headaches refractory to conventional pharmacological therapy. A 3T magnetic resonance imaging (MRI) of the brain with contrast was performed, which confirmed the diagnosis. Due to the failure of non-interventional treatment, he was treated with therapeutic endoscopic fenestration of the cyst. Postoperatively, he reported a complete resolution of the presenting symptoms.

Adult Onset Still's Disease: A Retrospective, Single-Center Study.

Background Adult-onset Still's disease (AOSD) is characterized by a classical triad of spiking fever, arthritis, and evanescent rash. It is one of the main causes of hospital admissions for fever of unknown origin and has an extended mean time to diagnosis. Therefore, it remains underdiagnosed relative to its aforementioned time frame. In this study, we attempt to highlight clinical and lab findings associated with AOSD. We then compare our diagnostic results with similar previous studies. Our results should help physicians not to miss this rare entity and make the diagnosis in a reduced time frame. Materials and methods This a retrospective, single-center study conducted at Dow University Hospital in Karachi, Pakistan. Thirty patients were enrolled in this study for six months (July 2019-December 2019). All patients were identified and recruited in the medical outpatient department using Yamaguchi's criteria. Written consent was obtained from all patients to access all their clinical charts. Demographics and prior results of laboratory investigations were retrieved from the chart files. Results In our study, the mean age of patients was 26.6 years. More specifically, males accounted for 53.3% (n=16) of cases, and females accounted for 46.6% (n=14) of total cases. The most common presenting clinical features included arthralgia (100%, n=30), fever (100%, n=30), myalgia (96.6%, n=29), large joint arthritis (66.6%, n=20), sore throat (50%, n=15), hepatomegaly (40%, n=12), splenomegaly (23.3%, n=7), skin rash (36.6%, n=11) and pericarditis (20%, n=6). Furthermore, none of our patients had cervical lymphadenopathy. The most commonly reported laboratory findings include leukocytosis (100%, n=30), hyperferritinemia (90%, n=27), elevated erythrocyte sedimentation rate (100%, n=30) and abnormal liver function tests (76.6%, n=23). Chest x-rays performed in all patients revealed no abnormalities in 83% of patients (n=25). All patients in our study sample (n=30) tested negative for antinuclear antibodies and rheumatoid factor. It was also noted that the mean duration of diagnosis in our patients was 5.98 weeks. The mean hospitalization period in our patients was 12.5 days. Furthermore, 16.7% of patients (n=5) suffered from disease relapse.  Conclusion Our study ascertains that the presence of certain clinical and laboratory findings strongly indicate a diagnosis of adult-onset Still's disease.

Frequency of Extravasation on Pericatheter Retrograde Urethrogram in Patients Who Undergo Posterior Urethroplasty.

Introduction Urethroplasty is the gold standard treatment for urethral stricture disease resulting from pelvic fractures, urethral manipulation, and straddle injuries. Post-operative morbidity depends on the presence of urethral catheterization with or without a suprapubic catheter (SPC). Urethral healing at the anastomotic site can be easily assessed using retrograde pericatheter urethrography (RPU). Post-operative removal of the catheter is traditionally performed on the 21st day following urethroplasty. However, some controversy still exists regarding the best feasible time of proper urethral healing and its assessment utilizing simple techniques. The duration of anastomotic healing differs depending on the type of procedure performed, but whether there is any significant difference in duration of healing at the anastomotic site according to the etiology of short-segment stricture urethra is still a dilemma. Materials and methods This was a descriptive case-series conducted for a duration of six months from September 2019 to February 2020 at the urology department of a tertiary care hospital in Karachi, Pakistan. A sample population of 135 patients aged 20-50 years with posterior urethral stricture who underwent posterior urethroplasty with disease duration of >12 months was included in the study. All patients were put on the next operation theater (OT) list for urethroplasty. After surgery, the patients were catheterized and were kept in the ward under observation for 48 hours and discharged on the 2nd post-operative day. All patients were followed weekly and RPU was performed on the 21st day following urethroplasty to assess the presence of extravasation and the collected data was entered into the proforma by the investigators. All statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 23.0. Results The mean age of our participants was 32.8±6.02 years. The mean duration of the procedure was 26.3±7.14 months. Extravasation cases were observed in less than one-fifth (n=22 out of 135, 16.3%) of the posterior urethral stricture patients in our study. Conclusions It is to be concluded that extravasation is fairly common in patients who undergo posterior urethroplasty. The prevalence varies depending on the assessment method, likely reflecting the treatment of somatic symptoms.

Therapeutic Implications of Altered Energy Metabolism in Migraine: A State-of-the-Art Review.

Currently, the management strategies aimed at the resolution of migraine are pharmacological. Most of these therapies are known to alter the serotonin balance of the brain. Furthermore, therapies blocking the calcitonin gene-related peptide (CGRP) have also proven to be quite effective in their treatments. However, apart from being expensive, these therapies do not influence premonitory and aura symptoms. This suggests an incomplete approach and an inadequate understanding of the migraine pathophysiology. Recent metabolic studies have indicated that migraine should be considered as an adaptive response to the mismatch between the cerebral energy reserves and expenditure. Therefore, understanding the underlying metabolism helps derive possible novel therapeutic modalities for migraines. In this review, we highlight the underlying metabolic abnormalities found in migraine patients. This will form the basis of our evidence-based discussion on metabolic therapeutic options for migraines.

Paraphenylenediamine (Kala Pathar) Poisoning at the National Poison Control Center in Karachi: A Prospective Study.

Introduction Suicide by self-poisoning is a common cause of death, especially in the younger population. More specifically, hair-dye poisoning is being increasingly used for suicide. Paraphenylenediamine (PPD), also known as "Kala pathar", is a highly toxic ingredient present in hair-dye that can cause death. Therefore, this study is designed to assess the demographics, clinical features, laboratory findings, and outcomes of PPD poisoning in patients admitted to the National Poison Control Center in Karachi, Pakistan. Materials and methods We conducted a prospective study for a period of six months at the National Poison Control Center, Karachi, Pakistan. A total of eight patients with PPD poisoning with no cardiac, liver, or renal co-morbidities were included in this study. The demographic characteristics, clinical features, laboratory findings, mode of intoxication, and route of intoxication were noted in a proforma. Furthermore, hospitalization time, tracheostomy status, mechanical ventilation status, and mortality rates were also recorded. For continuous variables, the means and SDs were calculated. Whereas for categorical data, percentages were calculated. Results In our study, the mean age of the patients was estimated at 25.38 ± 3.77 years. It was deemed that the majority of poisoning cases were intentional in nature (75%). These suicide cases were more commonly observed in young females (75%) who belonged to a low socioeconomic class (87.5%). The preferred route of administration was oral (87.5%). In 87.5% of the patients, the characteristic clinical features such as cervicofacial edema, dysphagia, dysphonia, and stridor were noted. During the later clinical stages of poisoning, clinical features such as rhabdomyolysis (62.5%), chocolate-colored urine (87.5%), hepatitis (75%), and acute renal failure (12.5%) were noteworthy. The mean ± SD of total leukocyte count (TLC), creatine phosphokinase (CPK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine and serum potassium were, respectively, noted at 10,500 ± 3,854.4 cells/mm3, 32.87 ± 11.36 IU/L, 1,239.1 ± 1,106.2 IU/L, 776.8 ± 1,149.8 IU/L, 2.125 ± 2.275 mg/dL, and 4.9 ± 1.094 mmol/L. In our patients, the mean intensive care unit stay was 8.25 ± 3.99 days. Emergency tracheostomy was performed in 25% of patients. Mechanical ventilation was required for 50% of our patients. Overall, the mortality rate observed in our study stands at 25%. Conclusion PPD poisoning is associated with a high rate of morbidity and mortality. Therefore, it is imperative for physicians to be mindful of the clinical characteristics and treatment options in order to optimally manage such cases of poisoning. In addition, the use of hair-dyes composed of highly lethal PPD should also be banned.

Frequency of Human Immunodeficiency Virus in Patients Admitted with Acute Stroke.

Introduction Stroke is a leading cause of chronic disability and death in both developing and developed countries. A significant proportion of stroke patients are human immunodeficiency virus (HIV) positive. About half of the HIV patients experience some sort of neurological deficit in their lifetimes. The exact reason for the occurrence of stroke in HIV infected patients is poorly understood. The purpose of our study is to determine the frequency of HIV among patients admitted with acute stroke. Materials and methods This cross-sectional study is conducted at a major metropolitan hospital in Karachi for six months. A total of 130 patients of stroke between the ages of 30 and 70 years of either gender were included in this study. A complete history was taken and a physical examination was performed. Each patient underwent a battery of tests that included HIV serology, lipid profile, electrocardiography (ECG), chest X-ray (posteroanterior (PA) view), and computed tomography (CT) scan of the brain. Carotid Doppler ultrasonography to assess carotid artery stenosis was also ordered. The means and standard deviations of age and cluster of differentiation 4 (CD4) cell count were calculated. The frequencies and proportions of gender, diabetes mellitus (DM), hypertension (HTN), smoking, obesity, dyslipidemia, carotid artery stenosis, and HIV status were calculated. Stratification was done by applying the chi-square test and assuming p-value ≤0.05 as significant. This helped analyze the association of age, gender, DM, HTN, smoking, obesity, dyslipidemia, and carotid artery stenosis to the frequency of HIV. Results The mean age of the study population was 55.54 ± 11.166 years. There were 39 (30%) patients <50 years of age while 91 (70%) patients were ≥50 years of age. Gender distribution showed that 86 (66.15%) patients were male, and 44 (33.85%) patients were female. Furthermore, 71 (54.62%) patients were hypertensive, 53 (40.77%) were diabetic, 62 (47.69%) were smokers, 49 (37.69%) were obese, 52 (40%) had dyslipidemia, and 77 (59.23%) had carotid artery stenosis. The frequency of HIV was noted at 24 (18.46%). The mean CD4 count was estimated at 241 ± 103.295 cells/mm3. Stratification showed a significant relationship between the frequency of HIV with only gender (p=0.01) and dyslipidemia (p=0.037). Conclusion HIV infection in patients with stroke is not uncommon. Patients who are male, younger in age, have dyslipidemia, belong to a low socioeconomic class, or have a bad sexual history are more likely to have HIV as an underlying cause of stroke. The exact pathogenesis of such a stroke and the role of antiretroviral therapy in the prevention and treatment of this group of stroke are not completely understood and need further analysis.

Successful Management of Coronary In-Stent Restenosis: A Case Report and Literature Review.

In-stent restenosis (ISR) arising in bare-metal stents and drug-eluting stents is difficult to manage. Herein, we report a case of ISR. Our patient had a history of percutaneous coronary intervention and presented with exaggerated angina symptoms despite being on antianginal medication. ISR was diagnosed with coronary angiography. In a clinical setting, it is treated with repeat revascularization of the blocked vessel with a re-stent placement or surgical approach.

Lamin A/C Cardiomyopathy with E203K Pathogenic Mutation.

Lamin A/C (LMNA) cardiomyopathy is an adult-onset, autosomal dominant, rapidly progressive cardiomyopathy which belongs to a spectrum of familial idiopathic cardiomyopathies. It is the most common type of familial dilated cardiomyopathy that is associated with conduction defects. A 76-year-old African American female with second-degree atrioventricular (AV) block presented for evaluation of persistent fatigue. Her family history was significant for sudden deaths of her son and brother at the age of 6 and 48 years, respectively, and AV block in her sister with a pacemaker implant at the age of 64 years. Physical examination was within normal limits. Electrocardiogram showed a Mobitz type II, second-degree AV block. Mild dilated cardiomyopathy was present on echocardiogram. Stress echocardiography had to be stopped due to premature ventricular contractions. Cardiac catheterization, coronary angiography, and cardiac MRI revealed no significant etiology for rhythm disturbance. Holter monitoring revealed intermittent bradycardia with a heart rate falling as low as 28 beats per minute, which led to the decision of dual-chamber pacemaker implantation. RhythmNext genetic testing (Ambry Genetics, Aliso Viejo, CA) was done due to the significant family history of sudden death; it revealed a heterozygous E203K pathologic mutation in the LMNA gene. Sudden death is the most common mode of death in LMNA cardiomyopathy; hence, the implantation of intracardiac cardioverter-defibrillator for primary prophylaxis was discussed with the patient. Clinicians should suspect LMNA cardiomyopathy in patients with rhythm disorders and family history of sudden death, which can help to identify individuals at risk and prevent sudden death by appropriate interventions.