Defining the Etiology of Renal Allograft Dysfunction Using Banff 2019 Classification: Correlation with Post-Transplant Duration and Creatinine Levels-A Comprehensive Analysis of 200 Renal Biopsies at a Tertiary Care Medical Center Hospital.

OBJECTIVE: Chronic kidney disease is a growing global health issue, contributing significantly to morbidity and mortality. The incidence of end-stage renal disease (ESRD) is approximately 100 per million population. Renal transplantation remains the cornerstone treatment for ESRD, with a projected 20-year survival rate of 60%. We aim to define the etiology of renal allograft dysfunction using the Banff 2019 classification by analyzing 200 renal allograft biopsies in correlation with creatinine levels across post-transplant time frames. METHODOLOGY: 200 renal allograft biopsies are analyzed using the recent Banff 2019 classification with creatinine levels and post-transplant duration correlation. RESULTS: The study included 150 (75%) male patients and 50 (25%) female patients, with the majority 78 (39%) representing the age group of 16-30 years. 36 (18%) biopsies were within 3-month post-transplant, while 92 (46%) were 2-year post-transplant. According to the Banff 2019 classification, 92 (46.0%) transplant rejection biopsies were identified, with most 54 (27%) exhibiting antibody-mediated rejection (Category 2), including 40 (20%) active acute antibody-mediated rejection (ABMR) and 14 (7.0%) chronic active ABMR. T-cell-mediated rejection (TCMR; Category 4) represented 12 (6%) biopsies, including 10 (5%) acute TCMR and 2 (1%) chronic active TCMR. Category 5, the miscellaneous group, represented 100 (50%) biopsies, out of which 32 (16%) exhibited calcineurin inhibitor (CNI) toxicity, 38 (19%) acute tubular necrosis, and 8 (4%) thrombotic microangiopathy. A notable variation in the dysfunction distribution across different post-transplant time frames indicated a temporal evolution in the underlying causes of allograft dysfunction. Specific Banff categories showed a robust association with renal dysfunction, potentially contributing to the elevation of creatinine levels and renal function deterioration. CONCLUSION: Our study highlights the intricate pathophysiology of renal allograft dysfunction. Most biopsies were attributed to ABMR whereas one-third of biopsies exhibited mixed lesions (ABMR and TCMR or ABMR and calcineurin inhibitor toxicity (CNIT)). Additionally, this study suggests that renal allograft rejection remains a significant contributor to graft dysfunction. A complex interplay between histological findings, Banff classification, and renal function is noted. A significant difference in the distribution of dysfunction across post-transplant time frames is noted suggesting a temporal evolution in the etiology of allograft dysfunction. Certain Banff categories demonstrate a stronger association with renal dysfunction that may influence creatinine level increase and renal function deterioration. In correspondence to the recent Banff 2019 guidelines for diagnosing ABMR, we emphasize the role of C4d staining on immunofluorescence or immunohistochemistry in allograft biopsies as imperative for timely diagnosis and immunosuppressant therapy adjustment, ultimately enhancing graft survival. Further research is needed to elucidate the underlying mechanisms driving renal dysfunction in different Banff categories, ultimately informing personalized management strategies for patients with renal allograft dysfunction. In line with the Banff 2019 guidelines for diagnosing ABMR, this study highlights the critical role of C4d staining through immunofluorescence or immunohistochemistry in allograft biopsies for early diagnosis and timely adjustment of immunosuppressive therapy, ultimately improving graft survival.

A study of wormhole solutions in f(Q,T) gravity using some viable shape functions.

This article examines static spherically symmetric wormhole (WH) solutions in f(Q,T) theory of gravity where Q represents non-metricity (NM) scalar while T is the trace of the stress-energy tensor. An anisotropic fluid configuration is taken into account to fulfill the task along with the linear form of the f(Q,T) model. For two different choices of the redshift function that are φ(r)=constant, φ(r)=(r0r)12 and for the shape functions, b(r)=r0+r0((rr0)γ-1),b(r)=r0log⁡(r+1)log⁡(r0+1), we construct the corresponding WH solutions. We examine the graphical behavior of the chosen shape functions and analyze all necessary and sufficient conditions for the existence of WH. We investigate the stability of obtained solutions and analyze how the energy conditions behave. We found that the null energy condition (NEC) is violated in a few regions of spacetime which shows the existence of traversable WHs in these regions. It is concluded that our results are viable for the positive values of theory parameters and within a range 0<γ<1 (the parameter of the shape function).

Diagnostic Accuracy of Fetal Anterior Abdominal Wall Thickness as an Early Sonographic Sign for Diagnosing Gestational Diabetes.

Introduction  Traditionally, different fetal variable measurements are used in ultrasound to assess fetal growth. Ultrasound can detect abnormal fetal growth. Gestational diabetes mellitus (GDM) is linked to higher fetal obesity as early as 20 weeks of pregnancy. The amount of fetal adipose tissue may be measured by measuring the thickness of the anterior abdominal wall. Measuring the thickness of the fetus's anterior abdominal wall (AAWT) is a straightforward procedure that may be performed alongside standard abdominal circumference measurements. Objectives  To check the diagnostic accuracy of fetal AAWT as an early sonographic sign for diagnosing GDM, keeping oral glucose tolerance test as the gold standard. Study design  This research was conducted using a cross-sectional analysis. Study place and duration The study was conducted in the Radiology Department at Rawalpindi Medical University and Allied Hospitals from July 10, 2019 to January 9, 2020. Materials and methods  Women between the ages of 18 and 45 who had a family history of type 2 diabetes and were at risk for developing GDM were recruited. Exclusions were made for diabetic women, those carrying multiples, and those with autoimmune diseases. The AAWT measurement of the fetus, which included the skin and subcutaneous tissue, was acquired using the traditional anterior cranial view, 2-3 cm lateral to cord insertion. Pregnant patients at risk for GDM underwent screening using an oral glucose tolerance test. Those exhibiting any two abnormal values were diagnosed with GDM. Results  The overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of fetal AAWT as an early sonographic sign for diagnosing GDM, with the oral glucose tolerance test as the gold standard, were 93.14%, 82.65%, 84.82%, 92.05%, and 88.0%, respectively. Conclusion  The study concludes that the diagnostic accuracy of fetal AAWT as an early sonographic indicator for identifying gestational diabetes is notably high.

A unified graph model based on molecular data binning for disease subtyping.

Molecular disease subtype discovery from omics data is an important research problem in precision medicine. The biggest challenges are the skewed distribution and data variability in the measurements of omics data. These challenges complicate the efficient identification of molecular disease subtypes defined by clinical differences, such as survival. Existing approaches adopt kernels to construct patient similarity graphs from each view through pairwise matching. However, the distance functions used in kernels are unable to utilize the potentially critical information of extreme values and data variability which leads to the lack of robustness. In this paper, a novel robust distance metric (ROMDEX) is proposed to construct similarity graphs for molecular disease subtypes from omics data, which is able to address the data variability and extreme values challenges. The proposed approach is validated on multiple TCGA cancer datasets, and the results are compared with multiple baseline disease subtyping methods. The evaluation of results is based on Kaplan-Meier survival time analysis, which is validated using statistical tests e.g, Cox-proportional hazard (Cox p-value). We reject the null hypothesis that the cohorts have the same hazard, for the P-values less than 0.05. The proposed approach achieved best P-values of 0.00181, 0.00171, and 0.00758 for Gene Expression, DNA Methylation, and MicroRNA data respectively, which shows significant difference in survival between the cohorts. In the results, the proposed approach outperformed the existing state-of-the-art (MRGC, PINS, SNF, Consensus Clustering and Icluster+) disease subtyping approaches on various individual disease views of multiple TCGA datasets.

Does Finding Cecal Adenoma Increase the Risk of Discovering More and Advanced Adenomas in the Remainder of the Colon?

OBJECTIVES: Adenomatous polyps are common, occurring in up to 25% of the population older than 50 years of age in the United States. Conflicting data are present in the literature about the impact of specific adenoma locations and the prediction on the number and advanced histology of adenomas elsewhere. With this study we aimed to review the association between cecal adenoma and the risk of discovering more and advanced adenomas in the remainder of the colon. METHODS: We performed a retrospective study of 1880 patients who received outpatient colonoscopies between June 2012 and December 2014 at the Veterans Affairs Medical Center in Oklahoma City. The data collected included patient demographics, indications for colonoscopy, smoking history, alcohol use, family history of colon cancer, quality of bowel preparation, number of adenomas, location, size of adenomas, and the histology of adenomas and colon cancer. RESULTS: The mean age of the study population was 61.6 ± 9.4 year, with 95% of the population being men. Cecal adenomas were found in 243 (12.9%) of patients. Patients with cecal adenoma tended to be older (65 ± 7 vs 61 ± 10, P < 0.0001), more likely to be men (97% vs 94%, P = 0.06) and less likely to have a colonoscopy done for screening indication (11% vs. 13%., P = 0.03). After adjusting for age, sex, indication, and quality of bowel preparation, patients with cecal adenoma were found to have a sixfold increase in finding ≥10 other adenomas elsewhere (4.5% vs 0.8% P = 0.0009) and a threefold increase in finding advanced adenomas (17.7% vs 9.9% P = 0.002) in the remainder of the colon. Stratifying by location, the increased risk was more pronounced in the right side (24.7% vs 8.9% P ≤ 0.0001) compared with the left side. CONCLUSIONS: Cecal adenoma is associated with an increased risk of finding more and advanced adenomas in the remainder of the colon, especially on the right side; therefore, the discovery of a cecal adenoma should prompt a more thorough evaluation of the entire colon, particularly the right colon.

Efficacy of Single Dose of Fosfomycin Versus a Five-Day Course of Ciprofloxacin in Patients With Uncomplicated Urinary Tract Infection.

INTRODUCTION AND OBJECTIVE: Treatment has become more challenging due to an aging population, polypharmacy and high prevalence of comorbid illness, antimicrobial antibiotic allergy or sensitivity, an increase in the number of individuals with underlying immunological or structural abnormalities, as well as the frequency of multidrug-resistant infections. Many multidrug-resistant bacteria are still susceptible to nitrofurantoin and fosfomycin, two ancient medicines. Their high urine concentrations and low toxicity give them an advantage over newer medications. This study aimed to compare the efficacy of a single dose of fosfomycin versus a five-day course of ciprofloxacin in patients with uncomplicated urinary tract infections. Methodology and data collection procedure: This randomized control trial was conducted in the Department of Medicine, Benazir Bhutto Hospital, Rawalpindi. A total of 46 patients were enrolled. Patients were divided randomly into two groups by using the lottery method. In group A, patients were given a single 3 g dose of oral fosfomycin. In group B, patients were given oral ciprofloxacin (500 mg) daily for five days. Then patients were followed-up in the Outpatient Department (OPD) for 28 days. After 28 days, patients were evaluated for resolution of symptoms (as per operational definition). Patients in whom symptoms would not be resolved were managed as per standard protocol. All this information was recorded on proforma. RESULTS: The average age of the patients in group A was 39.41±9.80 years while in group B that was 41.32±17.76 years. In both groups, 23 females were equally divided. The mean duration of symptoms in group A was 4.78±1.98 days while in group B was 4.95±1.29 days. The minimum duration of symptoms was three days and the maximum was 10 days. In group A, there were 15 (65.21%) patients with efficacy achieved, and among eight (34.78%) patients, efficacy was not achieved while in group B, there were 15 (65.21%) patients in which efficacy was achieved, and among eight (34.78%) patients, efficacy was not achieved. There was no significant association between efficacy and study groups as the p-value was not significant (p=0.87).  Conclusion: The conclusion of the study was that in the treatment of simple urinary infections, a single dose of fosfomycin had equal efficacy and tolerability as a five-day course of ciprofloxacin.

Perception of Parents of Thalassemic Child to Thalassemia in Pakistan.

Background Thalassemia is an inherited blood disorder characterized by reduced hemoglobin synthesis. Aim of our study is to assess the parental knowledge of thalassemia patients and their awareness regarding treatment and preventive measures against thalassemia. Methods It is an observational study done at Ali Zaib Foundation Thalassemia Center in Sahiwal, Pakistan, in May 2019. One hundred parents were enrolled in this study and a subjective questionnaire was used to collect data through direct structured survey method over a period of 30 days. Results There were parents of 62 (62%) male patients and 38 (38%) female patients, with a median age of 8.5 ± 6.2 years. Forty-three (43%) parents were illiterate while eight (8%) parents were highly educated. Sixty-six (66%) patients were born to parents with consanguineous marriages. Eighty-two (82%) parents were aware of thalassemia, 72 (72%) were aware of the risk of thalassemia due to cousin marriages, 76 (76%) parents were aware of the importance of prenatal diagnosis (PND), while 88 (88%) believed that a PND was beneficial. Fifty-two (52%) parents knew about thalassemia treatment, 80 (80%) were aware of the importance of blood screening, and 14 (14%) patients were receiving iron chelation therapy. Seventy-eight (78%) parents were aware of thalassemia prevention. All parents believed that the public requires awareness of the importance of premarital screening and PND. Conclusion Parental awareness regarding ß-thalassemia, its treatment and prevention is fair but far from ideal. Premarital screening, provision of accurate information to the public by professionals, and adequate screening and PND of at-risk families can significantly reduce the rates of thalassemias.

Designing and theoretical study of fluorinated small molecule donor materials for organic solar cells.

A recently synthesized photoactive donor named fluorinated thienyl-substituted benzodithiophene (DRTB-FT), modified with four novel end capped acceptor molecules, has been investigated through different electrical, quantum, and spectrochemical techniques for its enhanced electro-optical and photovoltaic properties. DRTB-FT was connected to 2-methylenemalononitrile (D-1), 2-methylene-3-oxobutanenitrile (D-2), 2-(2-methylene-3-oxo-2,3-dihydro-1H-inden-1-ylidene) malononitrile (D-3), and 3-methyl-5methylene-2-thioxothiazolidin-4-one (D-4) as terminal acceptor moieties. The architectural D-1 and D-3 molecules owe reduced optical band gap of 2.45 and 2.28 eV benefited from A-D-A configuration and have broaden maximum absorption band (λmax) at 617 and 602 nm in polar organic solvent (chloroform). Reduced optical band gap sets the ease for enhanced absorption. Reorganization energy of electron (λe) of D-3 molecule (0.00397 eV) was smaller among all which disclosed its greater mobility of conducting electrons (ICT). Larger values of dipole moment (µ) of D-1 (5.939 Debye) and D-3 (3.661 Debye) molecules in comparison to R indicated greater solubilities of the targeted molecules. Among the tailored molecules, D-3 showed the lowest binding energy of 0.25 eV in solvent phase and 0.08 eV in gaseous phase. The voltaic strength of the designed molecules was examined with respect to fullerene derivative (PC61BM) which exposed that D-1 is the best choice for achieving higher PCE. TDM (transition density matrix), DOS (density of states) analysis, and binding energies all were estimated at MPW1PW91/6-31G (d, p) level of DFT (density functional theory). All the architecture molecules show reduced band gap and high electron transfer rate due to the lowest reorganization energy (RE) of electron. The results show that there is greater contribution of acceptor and conjugated donor core towards the total absorption into the visible region of the spectrum. When tailored molecules D-1, D-2, D-3, and D-4 were blended with fullerene derivative polymer (PC61BM), they give high values of voltage at zero current level (Voc) compared to R.

B cell receptor (BCR) guided mechanotransduction: Critical hypothesis to instruct SARS-CoV-2 specific B cells to trigger proximal signalling and antibody reshaping.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, has spread around the globe with remarkable consequences for the health of millions of people. Despite the approval of mRNA vaccines to prevent the spread of infection, long-term immunity must still be monitored. Targeting and modifying virus receptor binding regions to activate B cell receptors (BCRs) is a promising way to develop long-term immunity against SARS-CoV-2. After the interaction of antigens, BCRs undergo series of signal transduction events through phosphorylation of immune receptor tyrosine activation motifs (ITAMs) to produce neutralizing antibodies against pathogens. BCRs intricate entity displays remarkable capability to translate the external mechanosensing cues to reshape the immune mechanism. However, potential investigations suggesting how SARS-CoV-2 specific B cells respond to mechanosensing cues remain obscure. This study proposes a sophisticated hypothesis explaining how B cells isolated from the CP of SARS-CoV-2 infected patients may undergo a triggered series of B cell activation, BCR dynamics, proximal signalling, and antibody production on PDMS-embedded in-vitro antigen-presenting structures (APCs). These studies could provide detailed insights in the future for the development of structural and therapeutic entanglements to fight against pathogens.

Primary Spinal Melanoma With Intra- and Extradural Extensions: A Rare Case.

Primary spinal melanoma (PSM) is a rare primary central nervous system melanoma with limited literature. A 30-year-old male presented with one year of progressive bilateral leg weakness and back pain. Physical examination revealed slightly decreased power and deep tendon reflexes of the lower extremities, decreased sensation at the level of T10, and normal anal sphincter and plantar reflexes. Magnetic resonance imaging (MRI) scan of the thoracolumbar spine revealed a hypointense lesion on T2-weighted and a hyperintense lesion on T1-weighted imaging at the level of T10 with mild extensions. The lesion was causing a mass effect on the spinal cord. The patient underwent laminectomy and near-total excision which showed a black, firm-to-hard, scarcely vascular extradural tumor extending from T10 to T11 that adhered to nerve roots. Histopathological examination and immunostaining with S-100 and Melan-A stains confirmed the diagnosis of malignant melanoma. Other imaging studies like brain computed tomography (CT) and positron emission tomography/computed tomography (PET/CT) scans, and chest X-ray were normal. On follow-up, the patient reported improvement in the power of his lower limbs with intact sensory function and sphincters. The first radiotherapy session was scheduled for six weeks postoperatively. There was no recurrence at a two-year follow-up. The possibility of a melanocytic tumor should be considered for a spinal lesion with paramagnetic properties as early surgical intervention is important for diagnosis and improved survival.

Population pharmacokinetics of meropenem among post-operative patients in Pakistan.

BACKGROUND: Meropenem, a potent carbapenem is considered the first choice for the empirical treatment of severe infections. Being a hydrophilic drug, more than 83% of the administered dose is eliminated through the renal route, and therefore, the kidney status of the patient may have a significant effect on meropenem clearance (CL). MATERIALS AND METHODS: The data of 205 samples obtained from 59 patients treated with meropenem at the General Hospital Lahore, Pakistan, was used for the development of a population pharmacokinetic (-popPK) model by using nonlinear mixed-effects modeling software. The effect of age, body weight, creatinine clearance (CRCL), and gender was observed on meropenem CL through a stepwise covariate modeling approach. Simulations of 1,000 mg q8h and 1,500 mg q12h over 3-hour infusion were performed based on the renal status of the patients. RESULTS: A two-compartment model was used for popPK analysis, and the values of the pharmacokinetic parameters for CL, V1, V2, and Q were 12.2 L/h, 21.7 L, 7.74 L, and 3.28 L/h, respectively. Meropenem CL was significantly influenced by CRCL, while no significant effect of body weight, age, and sex was observed. Both simulated dosage regimens were equally effective if CRCL of the patient was ≤ 100 mL/min, while 1,000 mg q8h produced better results if CRCL was > 100 mL/min. CONCLUSION: The CL of meropenem depends on the renal status of the patients. The model can be used for dosing simulations based on the CRCL of the patients in order to tailor the dose of meropenem in Pakistani patients.

Population pharmacokinetics of ciprofloxacin in Pakistani patients suffering from enteric fever.

BACKGROUND: Ciprofloxacin, a potent carboxy-fluoroquinolone is proved to be effective against some resistant strains of Gram-negative bacteria. Being a hydrophilic drug, it is primarily excreted through the kidney; almost 66% of the clearance from the body occurs through glomerular filtration. Therefore, renal status of the patient can have a significant effect on ciprofloxacin clearance. MATERIALS AND METHODS: A total of 158 samples were collected from 32 patients treated with ciprofloxacin in the Surgical Unit-I of Lahore General Hospital, Pakistan. The data was used for the development of a population pharmacokinetic model by using non-linear mixed-effect modeling (NONMEM) software. The influence of different covariates (age, sex, body weight, serum creatinine (SeCR), and creatinine clearance (CRCL)) was observed on ciprofloxacin clearance (CL) and volume of distribution (Vd) by stepwise covariate modeling (SCM). RESULTS: A one-compartment model was used for ciprofloxacin population pharma-cokinetik (popPK) analysis, and the values for ciprofloxacin CL and Vd in the final model were estimated at 19.8 L/h and 74.9 L, respectively. Among all the tested covariates, only CRCL was proven to have significant influence on ciprofloxacin CL. CONCLUSION: A strong relationship was found between the ciprofloxacin CL and renal status of the patients. The model can be used for dose tailoring in patients based on their CRCL values before the start of therapy with ciprofloxacin among Pakistani patients.

Infection Prevention and Control Measures at the Children Hospital Lahore: A My Child Matters Collaborative Project.

PURPOSE: Infection prevention among children with cancer is a major challenge at Children Hospital Lahore (CHL), a public health care facility in Pakistan with 1,000 new pediatric cancer admissions annually. The objective has been to reduce infections through collaboration between CHL and the St Jude Children's Hospital Global Infectious Disease program via a grant by the Sanofi Espoir foundation through the My Child Matters program. The aim of the current study was to describe the effect of the collaborative improvement strategy on existing infection prevention and control (IPC) standards at CHL. MATERIALS AND METHODS: Our work was a prospective before-and-after study to improve IPC standards. We compared the WHO Hand Hygiene Self-Assessment Framework and four modules of the St Jude modified Infection Control Assessment Tool (ICAT) scores over a 3-year period. Our strategy included creating a multidisciplinary team of pediatric oncologists, infectious disease physicians, nurses, a microbiologist, and a data manager; engaging in monthly online IPC mentoring sessions with St Jude Children's Hospital Global Infectious Disease program and My Child Matters mentors; performing daily inpatient health care-associated infection surveillance rounds; and performing regular hand hygiene training and compliance audits. RESULTS: Baseline needs assessment showed health care-associated infections identified by positive blood cultures as 8.7 infections per 1,000 patient-days. Deficient hand hygiene supplies, health education measures, and bed sharing of neutropenic patients were identified as major challenges. Our hand hygiene facility level, per WHO scores, increased from Inadequate to Intermediate/Consolidation by the end of the 3-year implementation (122 v 352 WHO Hand Hygiene Self-Assessment Framework scores). The sink:bed and hand sanitizer:bed ratios improved to 1:6 and 1:1, respectively. The ICAT general infection control module increased by 40% (45 v 78 ICAT scores) and hygiene compliance improved by 20%. CONCLUSION: Implementing a collaborative improvement strategy improved IPC standards in our center, which can be easily replicated in other pediatric oncology centers in lower- and middle-income countries.

Rare Association of Pneumomediastinum With Bilateral Pneumothorax.

Pneumomediastinum with bilateral pneumothorax is a clinical entity caused by infections, malignancy, or trauma, as in our case. Some patients present with pneumomediastinum secondary to trauma have esophageal, laryngeal, or tracheal injuries. A 16-year-old boy presented in the emergency department with complaints of shortness of breath and bruise on the chest after a history of the road traffic accident. Bilateral chest tube thoracotomy was done. Pneumomediastinum was suspected on X-ray chest and confirmed on computed tomography of the chest, which showed bilateral pneumothorax with pneumomediastinum. The patient was conservatively managed and discharged after 10 days.

Maintenance rituximab for relapsing thrombotic thrombocytopenic purpura: a case report.

BACKGROUND: Appropriate management to prevent relapses of acquired, autoimmune thrombotic thrombocytopenic purpura (TTP) is not clear. Rituximab (375 mg/m2 /week × 4) is effective treatment for acute episodes but it is not consistently effective for prevention of relapses. Maintenance rituximab, 375 mg/m2 /3 months for 2 years, is commonly used to prevent progression of follicular lymphoma, but the outcome of maintenance rituximab to prevent TTP relapses has been rarely reported. CASE REPORT: An 8-year-old girl was diagnosed with acquired TTP in 2008; her ADAMTS13 activity was less than 5%, with a functional inhibitor of greater than 8 Bethesda units/mL. She achieved remission with therapeutic plasma exchange, corticosteroids, and rituximab (375 mg/m2 /week × 4). During the following 6 years she had seven additional episodes. Each episode responded to therapeutic plasma exchange, sometimes requiring additional treatments (corticosteroids, rituximab, and cyclophosphamide). However, these treatments, as well as splenectomy and trials of cyclophosphamide and mycophenolate mofetil during clinical remissions, failed to prevent relapses. Her ADAMTS13 activity remained 8% or less throughout all of her remissions. Maintenance rituximab was begun in 2013: 500 mg (313 mg/m2 ) every 2-3 months × 5, then 600 mg (375 mg/m2 ) every 6 months × 2. After 1 year, her ADAMTS13 was 26%; after 2 years, 51%. During the past 3 years since stopping rituximab, she has remained well, with normal ADAMTS13 activity (70%-78%). CONCLUSION: Maintenance rituximab treatment may be effective for prevention of relapses in patients with acquired, autoimmune TTP, even when splenectomy and intensive immunosuppression, including multiple conventional courses of rituximab, fail to prevent subsequent relapses.

Pharmacological Treatment of Opioid-Induced Constipation Is Effective but Choice of Endpoints Affects the Therapeutic Gain.

BACKGROUND: Widespread opioid use has led to increase in opioid-related adverse effects like constipation. We examined the impact of study endpoints on reported treatment benefits. METHODS: Using MEDLINE, EMBASE, and ClinicalTrials.gov, we searched for randomized control trials targeting chronic opioid-induced constipation (OIC) and subjected them to meta-analysis. Data are given with 95% confidence intervals. RESULTS: Thirty trials met our inclusion criteria. Combining all dichotomous definitions of responders, active drugs were consistently more effective than placebo, with an odds ratio (OR): 2.30 [2.01-2.63; 15 studies], independent of the underlying drug mechanism. The choice of endpoints significantly affected the therapeutic gain. When time from drug administration to defecation was used, the OR decreased from 4.74 [2.71-4.74] at 6 h or less to 2.46 [1.80-3.30] at 24 h (P < 0.05). Using other response definitions, the relative benefit over placebo was 2.10 [1.77-2.50; 12 studies] for weekly bowel frequency, 2.03 [1.39-2.95; 9 studies] for symptom scores, 2.21 [1.25-3.90; 4 studies] for global assessment scales, and 1.27 [0.79-2.03; 7 studies] for rescue laxative use. CONCLUSION: While treatment of OIC with active drugs is more effective than placebo, the relative gain depends on the choice of endpoints. The commonly used time-dependent response definition is associated with the highest response rate but is of questionable relevance in a chronic disorder. The limited data do not clearly demonstrate a unique advantage of the peripherally restricted opioid antagonists, suggesting that treatment with often cheaper agents should be optimized before shifting to these novel expensive agents.

AmpC beta-lactamases in Klebsiella pneumoniae: An emerging threat to the paediatric patients.

OBJECTIVE: To determine the burden of AmpC beta-lactamase producing Klebsiella pneumoniae and its antimicrobial profile among paediatric patients. METHODS: This cross-sectional study was conducted at the Microbiology Department of The Children's Hospital and the Institute of Child Health in Lahore, Pakistan, from May 2014 to April 2015, in which isolates of Klebsiella pneumoniae were screened by using the cefoxitin disc. Confirmation was done by inhibitor-based method using 400 micro grams of boronic acid dispensed on the cefoxitin discs. The zone sizes of cefoxitin with and without the boronic acid were compared. The antimicrobial susceptibility testing was performed using Kirby Bauer disc diffusion method. RESULTS: Positive cultures yielded 585 Klebsiella pneumoniae out of which 220(37.6%) strains were AmpC beta-lactamase-positive on the basis of cefoxitin screening and 126(21.53%) were positive on the basis of inhibitor-based confirmatory method. Most of the infected patients 73(57.9%) were neonates. All AmpC beta-lactamase-producing strains were resistant to cephalosporins. They also exhibited resistance to ciprofloxacin 109(86.5%), amikacin 98(77.8%), levofloxacin 8(77.8%), cefoperazone-sulbactam 81(64.3%), piperacillin-tazobactam 82(65.1%), meropenem, 56(44.4%) and imipenem 32(25.4%). CONCLUSIONS: Prompt identification of AmpC beta-lactamases using inhibitor-based confirmatory test can help reduce the burden of these pathogens.

Successful Antimicrobial Treatment of Phlegmonous Gastritis: A Case Report and Literature Review.

Phlegmonous gastritis is an uncommon acute bacterial infection of the stomach that carries a fatal prognosis in spite of the advent of antibiotics. A high index of suspicion is required in patients with risk factors. An immunocompromised state is identified as one of the most important risk factors. We hereby report a case of successful antimicrobial treatment of phlegmonous gastritis in a patient who was receiving intensive chemotherapy for acute myelogenous leukemia. We have also carried out a review of literature over the past ten years. Streptococcus pyogenes is identified as the most common causative organism, and patient presentation is usually nonspecific. Conservative treatment with prompt institution of antibiotics can lead to rapid resolution in the majority of patients.