Adjuvant Radiofrequency Ablation Along With Stenting Versus Stenting Alone for Biliary Tree Drainage in Patients With Malignant Biliary Strictures: A Systemic Review and Meta-analysis.

OBJECTIVE: This metanalysis aims to assess the efficacy and safety of biliary stenting along with radiofrequency ablation compared with stents alone to treat malignant biliary obstruction (MBO) due to extrahepatic biliary strictures secondary to cholangiocarcinoma, pancreatic cancer, and metastatic cancer. METHODS: A systemic search of major databases through April 2022 was done. All original studies were included comparing radiofrequency ablation with stenting versus stenting alone for treating malignant biliary strictures. The primary outcomes of interest were the difference in the mean stent patency and overall survival (OS) days between the 2 groups. The secondary outcome was to compare the adverse events of the 2 groups. The mean difference in the stent patency and OS days was pooled by using a random-effect model. We calculated the odds ratio to compare the adverse events between the 2 groups. RESULTS: A total of 13 studies with 1339 patients were identified. The pooled weighted mean difference in stent patency was 43.50 days (95% CI, 25.60-61.41), favoring the RFA plus stenting. Moreover, the pooled weighted mean difference in OS was 90.53 days (95% CI, 49.00-132.07), showing improved survival in the RFA group. Our analysis showed no statistically significant difference in adverse events between the 2 groups OR 1.13 (95% CI, 0.90-1.42). CONCLUSION: Our analysis showed that RFA, along with stent, is safe and is associated with improved stent patency and overall patient survival in malignant biliary strictures. More robust prospective studies should assess this association further.

Evaluation of soil texture classification from orthodox interpolation and machine learning techniques.

The current investigation examines the effectiveness of various approaches in predicting the soil texture class (clay, silt, and sand contents) of the Rawalpindi district, Punjab province, Pakistan. The employed techniques included artificial neural networks (ANNs), kriging, co-kriging, and inverse distance weighting (IDW). A total of 44 soil specimens from depths of 10-15 cm were gathered, and then the hydrometer method was adopted to measure their texture. The map of soil grain sets was formulated in the ArcGIS environment, utilizing distinct interpolation approaches. The MATLAB software was used to evaluate soil texture. The gradient fraction, latitude and longitude, elevation, and soil texture fragments of points were proposed to an ANN. Several statistical values, such as correlation coefficient (R), geometric mean error ratios (GMER), and root mean square error (RMSE), were utilized to evaluate the precision of the intended techniques. In assessing grain size and spatial dissemination of clay, silt, and sand, the effectiveness and precision of ANN were superior compared to kriging, co-kriging, and inverse distance weighting. Still, less than a 50% correlation was observed using the ANN. In this examination, the IDW had inferior precision compared to the other approaches. The results demonstrated that the practices produced acceptable results and can be used for future research. Soil texture is among the most central variables that can manipulate agriculture plans. The prepared maps exhibiting the soil texture groups are imperative for crop yield and pastoral scheduling.

Structural and thermal investigation of lignocellulosic biomass conversion for enhancing sustainable imperative in progressive organic refinery paradigm for waste-to-energy applications.

The depletion of finite fossil fuel reserves and the severe environmental degradation resulting from human activities have compelled the expeditious development and application of sustainable waste to energy technologies. To encapsulate energy and environment in sustainability paradigm, bio waste based energy production is need to be forged in organic bio refinery setup. According to world bioenergy association, biomass can cover 50 % of the primary energy demand of the world. Therefore, the present study focuses on reforming the energy mix for a clean energy generation, where, sample composition of cotton stalk was acidified in dilute (5% wt.) hydrochloric acid (HCL) for analyzing material burnout patterns in biomass conversion systems utilized in organic bio refinery sector. Advanced thermochemical burning technique, which includes pyrolysis and combustion was applied at four different leaching times from 0 to 180 min under nitrogen environment from 0 °C to 500 °C and air from 500 °C to 900 °C, respectively. Different analyses including proximate, ultimate, gross calorific value (GCV), thermos-gravimetric, kinetic, XRD, FTIR, SEM-EDS were used for analyzing the degradation of demineralized cotton stalk at different treatment rates. Proximate study demonstrated that cotton stalk leaching for 180 min has efficiently infused HCL, leading in a significant increase in fixed carbon and higher heating value of 20.23 % and 12.48%, respectively, as well as a reduction in carbon footprint of around 54.80%. The findings of proximate was validated by GCV analysis and CHNS analysis as value of carbon and hydrogen has shown increasing behavior with the time delay in demineralization Thermo-gravimetric and derivative thermo-gravimetric data analyses shows an increasing trend of conversion efficiency, with the maximum increase of 98 % reported for sample 3H.TT.DEM. XRD characterization has reported 23° to 25° angle for all the observed peaks. Sample 3H.TT.DEM has shown maximum angle inclination along with matured crystalline peak. The latter observations has been validated by FTIR spectroscopy as sample 3H.TT.DEM has reported maximum O-H group formation. Sample 3H.TT.DEM has reported lowest activation energy of 139.51 kJ*mole-1 and lowest reactivity of 0.000293649%*min 0C, due to moderate and stable reactiveness. In SEM examination, increment in pore size and number of pores within the structural matrix of cotton stalk was observed with the enhancement in acidulation process. Furthermore, in EDS analysis, 3H.TT.DEM has shown most balanced distribution of the elements. In this research, sustainable transformation of biomass is envisioned to improve the waste bio refinery system, significantly contributing to the achievement of Sustainable Development Goals 7, 12 and 13.

Robust Output Feedback Stabilization and Tracking for an Uncertain Nonholonomic Systems with Application to a Mobile Robot.

This paper presents a novel robust output feedback control that simultaneously performs both stabilization and trajectory tracking for a class of underactuated nonholonomic systems despite model uncertainties, external disturbance, and the absence of velocity measurement. To solve this challenging problem, a generalized normal form has been successfully created by employing an input-output feedback linearization approach and a change in coordinates (diffeomorphism). This research mainly focuses on the stabilization problem of nonholonomic systems that can be transformed to a normal form and pose several challenges, including (i) a nontriangular normal form, (ii) the internal dynamics of the system are non-affine in control, and (iii) the zero dynamics of the system are not in minimum phase. The proposed scheme utilizes combined backstepping and sliding mode control (SMC) techniques. Furthermore, the full-order high gain observer (HGO) has been developed to estimate the derivative of output functions and internal dynamics. Then, full-order HGO and the backstepping SMC have been integrated to synthesize a robust output feedback controller. A differential-drive type (2,0) the wheeled mobile robot has been considered as an example to support the theoretical results. The simulation results demonstrate that the backstepping SMC exhibits robustness against bounded uncertainties.

Impact of haemodialysis on plasma carnitine concentrations in haemodialysis patients.

Objective: To evaluate the impact of haemodialysis on plasma carnitine levels. METHODS: The cross-sectional study was conducted from April 20, 2020 to May 10, 2022, at the dialysis unit of the nephrology ward of Jinnah Postgraduate Medical Centre, Karachi, and the Pakistan Navy Ship Shifa Hospital, Karachi, in collaboration with the Department of Biochemistry, University of Karachi, and comprised patients of either gender aged >18 years. They were divided into chronic kidney disease group A and end-stage renal disease group B. Control group C included subjects from the general population. Free carnitine and total carnitine values were detected using enzyme-linked immunosorbent assay. Acyl carnitine was estimated by applying the standard formula, and the ratio between acyl carnitine and free carnitine was calculated for accurate assessment of the carnitine status. Data was analysed using SPSS 23. RESULTS: Of the 203 subjects, 143(70.44%) were cases and 60(29.55%) were controls. Among the cases, 120(84%) were recruited from Jinnah Postgraduate Medical Centre and 23(16%) from Pakistan Navy Ship Shifa Hospital. There were 60(29.55%) patients in group A, 83(40.88%) in group B and 60(29.55%) in group C. The mean age in group A was 47.90 5.±65 years, it was 44.10 ±8.92 years in group B and 40.90 ± 6.73 years in group C. There was a significant difference related to free carnitine, total carnitine, acyl carnitine values and the ratio between acyl carnitine and free carnitine values in groups A and B compared to control group C (p<0.05). Conclusion: Patients on maintenance haemodialysis developed were found to have developed carnitine deficiency.

Behavioural impacts of following administration of Ficus carica leaves extract in animal model of acute and chronic unpredictable mild stressed exposed rats.

Stress is described as a noxious stimulus that affects the health of an individual and alters body homeostasis resulting in changes the individual behavioural and metabolic condition. Synthesis of drug from plants has main interest due the significant medicinal values. The recent investigation was designed to examine the pharmacological impacts of Ficus carica leaves extract on stress. In this experiment, the rodents were randomly distributed as (n=6) control rats were kept at standard condition, second group of rats were exposed with different stressors and Third group of rodents was exposed to stress and treated with extract of ficus carica leaves at the dose of 100 mg/kg. Acute behavioural alteration was observed after 7 days and prolonged impact was monitored after the 28 days. The current finding showed that administration of Ficus carica leaves extract produced anxiolytic behaviours and decreased depression like symptoms in CUMS treated rats. It also increased stimulatory, ambulatory, locomotor activity and enhanced spatial working memory and recognition memory in CUMS exposed rats. So, it can be concluded from recent study that leaves of Ficus carica can be utilized as secure drug for curing physiological stress with less side effect profile.

Genome Editing and Fatty Liver.

Fatty liver disease is characterized as nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Fatty liver disease is one of the most common causes of chronic liver disease worldwide among adults and children. It is characterized by excessive fat accumulation in the liver cells. It has a genetically heterogenous background with complex pathogenesis and progressions and is accompanied by significant morbidity, mortality, and healthcare costs. NAFLD's risk factors include metabolic syndrome, abdominal obesity, type 2 diabetes, and atherogenic dyslipidemia. ALD is associated with the excessive consumption of alcohol. Here, we describe the functions of various proteins encoded by gene variants contributing to the pathogenesis of nonalcoholic fatty liver disease and alcoholic fatty liver disease. Advancements in genome engineering technology have generated various in vivo and in vitro fatty liver disease models reflecting the genetic abnormalities contributing toward fatty liver disease. We will discuss currently developed different ALD and NAFLD models using the clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) genome editing tool.Furthermore, we will also discuss the salient features of CRISPR/Cas9 editing technology and Cas9 variants such as prime and base editors to replicate genetic topographies linked specifically to ALD and NAFLD. The advantages and limitations of currently available genome delivery methods necessary for optimal gene editing will also be discussed in this review. This review will provide the essential guidance for appropriate genome editing tool selection and proper gene delivery approaches for the effective development of ALD and NAFLD models, leading to the development of clinical therapeutics for fatty liver disease.

Psychopharmacological impact of ferulic acid on depressive-like behaviors induced by high fat diet in rats models of depression.

Previous studies have been demonstrated that high fat diet can leads to the development of obesity. Obesity is strongly linked with several kinds of neurological and physiological disorders such as type 2 diabetes and cardiovascular diseases. Furthermore studies also suggested that obesity may cause behavioral changes that mainly deal with less locomotor activity and anxiety obesity linked behavioral changes induced by HFD. By using different parameters like growth rate, food intake, levels of anxiety and locomotor activity the finding of this study showed that, that repeated administration of ferulic acid has great profound effect on impairments that were caused by HFD. In our experiments we have observed that those rats which were on HFD and were treated with water only was seemed to be more depressed, less active, and more anxious than those which were administered by ferulic acid doses. From these results we can also suggest that there must be disturbance in the levels of neurotransmitters in an obese individual that caused such kind of changes in the body. This study has implications in the recovery of the changes in the body that were produced by HFD. And ferulic acid can be used as the drug to cure behavioral consequences that were induced by HFD.

Assessment of neuropharmacological consequences induced by dexamethasone administration in rats model of neurodegenerative diseases.

Stress is a well-known and frequently used term among present generation. It has been referred to the response of body to any challenge for a change. It is a natural process and our body is designed to cope with it. However, if stress becomes chronic, it can lead to mental health problems. Stress due to the prolonged administration of glucocorticoid is enabled to produce impressive alterations in rats model shoeing depressive like behavior. In this investigation; purpose was to study the impact of episodic treatment of dexamethasone with respect to behavioral changes in rats. It was hypothesized that repeated administration of dexamethasone could increase stress and thus, psychological stress leading to mood disorders and behavior deficits in rats. Rats were injected daily with DEX (10 mg/ml/kg, orally) and the different behavioral models of the animals were assessed. DEX-treated rats exhibited depressive behavior like greater time to start mobility in a novel environment and elevated anxiety-like behavior in elevated plus maze. However, time spent in light compartment was shorter with repeated administration of DEX. From results it is demonstrated that the administration of DXM for weeks induced stress and consequently, induced a depression-like behaviors in rats models.

An Integrated Fuzzy Analytic Hierarchy Process (AHP) Model for Studying Significant Factors Associated with Frequent Lane Changing.

Frequent lane changes cause serious traffic safety concerns, which involve fatalities and serious injuries. This phenomenon is affected by several significant factors related to road safety. The detection and classification of significant factors affecting lane changing could help reduce frequent lane changing risk. The principal objective of this research is to estimate and prioritize the nominated crucial criteria and sub-criteria based on participants' answers on a designated questionnaire survey. In doing so, this paper constructs a hierarchical lane-change model based on the concept of the analytic hierarchy process (AHP) with two levels of the most concerning attributes. Accordingly, the fuzzy analytic hierarchy process (FAHP) procedure was applied utilizing fuzzy scale to evaluate precisely the most influential factors affecting lane changing, which will decrease uncertainty in the evaluation process. Based on the final measured weights for level 1, FAHP model estimation results revealed that the most influential variable affecting lane-changing is 'traffic characteristics'. In contrast, compared to other specified factors, 'light conditions' was found to be the least critical factor related to driver lane-change maneuvers. For level 2, the FAHP model results showed 'traffic volume' as the most critical factor influencing the lane changes operations, followed by 'speed'. The objectivity of the model was supported by sensitivity analyses that examined a range for weights' values and those corresponding to alternative values. Based on the evaluated results, stakeholders can determine strategic policy by considering and placing more emphasis on the highlighted risk factors associated with lane changing to improve road safety. In conclusion, the finding provides the usefulness of the fuzzy analytic hierarchy process to review lane-changing risks for road safety.

Magnitude and pattern of anxiety levels with gender wise predilection of coping strategies amid resident doctors of emergency department.

Objectives: To screen and assess the severity level of anxiety, its influencing factors along with the gender-wise predilection of coping strategies among resident doctors working in accident and emergency departments. Methods: A transverse study was conducted amongst 260 resident doctors of accident and emergency department of different teaching hospitals of Karachi from October 2020 until March 2021. A demographic sheet containing questions related to factors, GAD-7 (Generalized Anxiety Disorder) and Brief COPE were used to measure the severity level of anxiety and coping strategies. Data was scored according to the standard scoring procedure for each subscale and for further statistical analysis SPSS Version 21 was used. Results: Out of all participants, 68.1% were <30 years of age, 63.1% were females while 54.2% were single. The findings of the study showed the prevalence of anxiety within the range of normal (38.1%), mild (35.0%), moderate (16.9%) and severe (10.0%). Gender (p= 0.001), marital status (p= 0.040) and job satisfaction (p= 0.007) among resident doctors were significantly associated with level of anxiety. Deemed to coping strategies, the most frequently were planning (n=145, 90.0%), acceptance (n=141, 87.6%), and religion (n=137, 85.1 %). All coping strategies were mostly opted by females except substance abuse. Conclusion: More than a half of the resident doctors manifested with mild to severe anxiety disorder, which highlights the need for psychological support programs to minimize anxiety levels and to ensure a healthy environment at workplace for the health practitioners.

Inhibition of drug induced Parkinsonism by chronic supplementation of quercetin in haloperidol-treated wistars.

Haloperidol is a neuroleptic medication that is used to treat a wide range of neuropsychiatric conditions. It has been shown to produce medicinal effects against hyperactivity, agitation and mania, as well as schizophrenia. Long-term usage of haloperidol raises the risk of acquiring a neurological condition like Parkinson's disease. Haloperidol causes drug-induced Parkinsonism (DIP) by blocking central dopamine receptors and causing extrapyramidal symptoms during long-term treatment. Quercetin has been shown to reduce the loss of striatal neurons, which may enhance motor capabilities and protect against agents that cause the production of reactive oxygen species (ROS). As a result, present study intended to evaluate the efficacy of quercetin on haloperidol-related motor abnormalities. To develop behavioral impairments, rats (n=24) randomly divided to control and haloperidol group for four weeks. The animals were split into four groups after four weeks: Control, quercetin, haloperidol and haloperidol + quercetin. Animals were administered haloperidol i.p injections of 5mg/kg and quercetin (100mg/kg) orally for 21 days. The treatment of haloperidol-treated rats with quercetin was successful in reversing the haloperidol alterations. It decreased animal food intake and alleviated anxiogenic behavior. The chronic treatment of quercetin further reduced the movement abnormalities in animal model of drug induced pseudo-Parkinson.

Quercetin impact against psychological disturbances induced by fat rich diet.

Obesity is a metabolic disease which promotes by consuming fat rich diet. The consequences may include leptin resistant and initiation of metabolic syndromes. Beside the fact, obesity has psychological impacts it act as a signal of depression by stimulating endogenous stress stimulation. Quercetin is a natural polyphenol, considered as nutraceutical agent which produce antioxidant effects. It is reported to promote energy expenditure and protective mechanism against obesity. This presented work was designed to observe the effects of quercetin on high fat diet treated obese animals with impaired psychological behavior. The study comprised on 36 animals, divided in to different groups as follow: I Normal Diet and II. High fat diet. After the induction of obesity both groups divided in to further three subgroups as control, Quercetin and sertraline. Food intake and body weight along with behavioral analysis for four weeks were done for the assessment of anti-obesity and antidepressant effects of quercetin. The results showed the effective treatment of quercetin in obese animals, it significantly reduced the food intake and body weight of animals. The behavioral test showed the increased locomotor activity in the activity box and improved psychological behavior in quercetin-treated rats in the open field and light-dark box. It is concluded from the present study that quercetin exhibits the ameliorative effects against obesity and associated neuroendocrine alterations.

Controlled release floating drug delivery system for proton pump inhibitors lansoprazole: In-vitro, In-vivo floating and pharmacokinetic evaluation.

Lansoprazole (LPZ) show poor bioavailability because of first pass effect and absorption factors. The floating delivery systems could reduce fluctuations in plasma drug concentration through maintaining desirable plasma drug concentration. The objective of present study was to enhance bioavailability despite first pass effect through continuous availability of drug from floating system. Gum tragacanth (GT) and itaconic acid (IA) based floating hydrogels (FH) were synthesized. Parameters optimized were; microwave radiation exposure time, pH, GT:IA ratio and concentration of the glutaraldehyde. Optimized FH were evaluated for entrapment efficiency (% EE), in-vitro release, FTIR, SEM, and in- vitro and in-vivo floating study. Finally, pharmacokinetic was evaluated in ulcer-induced SD rats. Grafting percentage, swelling ratio and %EE of LPZ was 115%, Ì´250% and 90%, respectively. Microwave radiation exposure time, pH of reaction medium, GT:IA ratios and cross linker concentration were 2 min, pH 5, ratios 2:1 and 0.02%, respectively. The optimized FH showed acceptable floating behavior. The X-ray images revealed that hydrogels remained floated over gastric contents up to 24 hours. The in-vitro release and pharmacokinetics revealed availability of LPZ upto to 24h in-vitro and in ulcer-induced SD rats, respectively. The present hydrogels based floating system of lansoprazole is capable to extend the gastric residence time upto 24 hours.

Association amid the comorbidity of Diabetes Mellitus in patients of Active Tuberculosis in Pakistan: A matched case control study.

OBJECTIVES: This study aims to test the association between diabetes and tuberculosis. METHODS: It is a matched case control study conducted in tertiary care hospitals in 2019-2020. Cases and controls were 144 each, selected on the basis of an odds ratio of 2 at 95% confidence interval with a significance level of 5%. Cases of pulmonary tuberculosis were selected through consecutive sampling technique, either visiting OPD or admitted in hospital. Controls were taken from the general population and frequency matching was done based on age, gender and socioeconomic status. Data was collected through structured questionnaire after taking written consent. Data was analyzed on SPSS version 23. Binary Logistic regression model was applied for finding association between the risk factors and the disease. P value <0.05 was considered statistically significant. RESULTS: Out of all cases and controls, 45% and 20% were diabetics respectively. The association between the risk factors and tuberculosis was estimated by univariate analysis, positive association was found between diabetes and tuberculosis (OR= 3.32), a high frequency of diabetes in cases as compared to controls were observed with a highly significant p- value (<.001). CONCLUSIONS: This study provides evidence for a strong positive association between tuberculosis and diabetes.

Association of subjective memory complaints amid patients of Diabetes Mellitus Type II and Hypertension.

BACKGROUND AND OBJECTIVE: Subjective memory complaints (SMCs) are suggested to predict dementia at a very early stage. However, association of SMCs with known risk factors of dementia namely diabetes mellitus Type-2 diabetes and hypertension (HTN) remain unexplored which is the main aim of this study. The objective of the study was to investigate the association of SMC with diabetes mellitus type 2 (DM2) and hypertension (HTN). METHODS: The associations of diabetes and hypertension, with SMCs has been tested in 500 participants from a tertiary care hospital of Karachi during 2017. Diagnosed cases of diabetes and hypertension were included through convenient sampling. Healthy attendants of patients were interviewed for the reference group. SMCs were assessed through a 14-item SMC questionnaire. RESULTS: Sample included 114 patients with only diabetes and hypertension each, 103 with both diabetes and hypertension and 169 healthy participants. Compared to healthy adults, persons with diabetes and hypertension had higher SMCs (difference, 0.88, 95% CI: 0.22, 1.54) (difference, 1.06, 95% CI: 0.40, 1.71) respectively, in fully adjusted models. CONCLUSIONS: Compared to healthy adults of working age-group, persons with diabetes and hypertension were more likely to have SMCs. Assessment and early detection of SMCs in persons with diabetes and hypertension might be informative to provide a window for effective interventions to maintain cognitive health.

Single-Agent Cyclosporine for Graft-versus-Host Disease Prophylaxis in Patients with Acquired Aplastic Anemia Receiving Fludarabine-Based Conditioning.

Cyclosporine (CsA) combined with short-course methotrexate is considered standard-of-care graft-versus-host disease (GVHD) prophylaxis for patients with severe aplastic anemia (AA) who undergo transplantation using cyclophosphamide (Cy) plus anti-thymocyte globulin (ATG) conditioning. However, there is no consensus on optimal post-transplant GVHD prophylaxis for patients undergoing matched related donor (MRD) transplantation using fludarabine (Flu)-based conditioning. We conducted a single-center retrospective analysis of patients with acquired AA (n = 106) undergoing MRD transplantation from July 2007 through January 2019. All patients received Flu-Cy-ATG conditioning and single-agent CsA as GVHD prophylaxis. Median age of the study cohort was 20 years (range, 3 to 52) and male to female ratio was 3.8:1. Median time from diagnosis to transplant was 11.5 months (range, 2.8 to 62). Graft source was bone marrow harvest in 71 (68%), combined bone marrow and peripheral blood stem cells in 34 (31%), and peripheral blood alone in 1 (1%) patient. Cumulative incidence of neutrophil engraftment at day 28 was 93.4% (95% confidence interval [CI], 87.3% to 97.1%) while that of platelet engraftment at day 100 was 90.5% (95% CI, 84% to 96%). Cumulative incidence of primary graft failure at day 28 was 6.6% (95% CI, 4% to 8%) while secondary graft failure occurred at a median of 190 days (range, 90 to 415) at a cumulative incidence of 3.7% (95% CI, 2% to 5%). Cumulative incidence of grade II to IV acute GVHD at day 100 was 3.8% (95% CI, 1.4% to 9.9%), while a 1-year probability of chronic GVHD was calculated as 7.5% (95% CI, 2.6% to 15%). Median follow-up post-transplant was 61 months (range, 6 to 144). Overall survival was 84.9%, disease-free survival was 80.2%, and GVHD-free relapse-free survival was 76.3%. This study indicates that single-agent cyclosporine is a feasible option for GVHD prophylaxis in MRD hematopoietic stem cell transplantation using Flu-Cy-ATG conditioning and is associated with very low rates of acute and chronic GVHD.

Evaluation of Serum Free Light Chain in Diagnosis and Monitoring of Plasma Cell Disorders.

OBJECTIVE: To determine diagnostic accuracy of serum free light chain assay compared to serum and urine protein electrophoresis in plasma cell disorders. STUDY DESIGN: Descriptive cross-sectional study. PLACE AND DURATION OF STUDY: This study was conducted in the Immunology Department, Armed Forces institute of Pathology (AFIP), Rawalpindi, from May 2017 to May 2018. METHODOLOGY: Patients referred to AFIP for diagnosis of plasma cell disorders or for monitoring while receiving treatment were included in study. They were tested for serum protein electrophoresis (SPE), urine protein electrophoresis (UPE), immunofixation (IF), and serum free light chain assay (sFLC). IF was used as the reference standard. Test results were compared in terms of sensitivity, specificity, positive or negative predictive value, and accuracy index. RESULTS: During the study period 220 patients were tested for plasma cell disorders. One hundred and sixty-seven patients tested positive. One hundred twenty-nine patients had multiple myeloma, 13 plasmacytoma, 11 monoclonal gammopathy of undetermined significance, 6 amyloidosis, 6 POEMS, and 2 Waldenstrom macroglobulinemia. SPE had a sensitivity of 70.5%, specificity of 100%; sFLC had a sensitivity of 87%, specificity of 81%; and UPE had a sensitivity of 23.5%, specificity of 97%. Accuracy index was 80.5% for SPE, 85% for sFLC, and 54% for UPE. When taken together, SPE and UPE had a combined sensitivity of 72%, specificity 97%, and accuracy index 80.5%. SPE and sFLC had combined sensitivity of 98.6%, specificity 84.3%, and accuracy index 94%. CONCLUSION: Combination of SPE and sFLC had the highest sensitivity and accuracy index for diagnosis and monitoring of plasma cell disorders compared with conventional tests.

Efficacy of newer modalities in the management of indirect hyperbilirubinaemia at a secondary care hospital: A prospective study from 2015-2018.

OBJECTIVE: To evaluate the efficacy of current practices and new modalities for the management of neonatal indirect hyperbilirubinaemia. METHODS: The prospective study was conducted at King Khalid Hospital, Al Majmaah, Saudi Arabia, from September 2015 to September 2018, and copmprised neonates with hyperbilirubinaemia who were managed using the National Institute for Health and Clinical Excellence 2010 guidelines. The outcomes were measured in terms of decrease in total serum bilirubin and clinical improvement. Data was analysed using SPSS 25. RESULTS: Of the 233 subjects, there were 119(51%) girls and 114(49%) boys. Phototherapy was used in 162(69.5%) cases, intensive phototherapy in 36(15.5%) and intravenous immunoglobulin in 35(15%). Exchange transfusion was done in 2(0.85%) patients. All the 233(100%) patients improved with the management and total serum bilirubin significantly reduced (p<0.05). CONCLUSIONS: Newer techniques were found to have a vital role in the management of neonatal hyperbilirubinaemia.

Outcome of Fludarabine-Based Conditioning in High-Risk Aplastic Anemia Patients Undergoing Matched Related Donor Transplantation: A Single-Center Study from Pakistan.

Despite excellent transplant outcomes of aplastic anemia (AA) in developed countries, management in developing countries is challenging because of delay in the diagnosis, use of family donors for transfusions, and higher infection risk pretransplant. These factors can lead to allo-immunization, increased risk of graft failure, graft-versus-host disease (GVHD), and transplant-related mortality, leading to unfavorable outcomes. Conventional cyclophosphamide (Cy) and antithymocyte globulin (ATG) are associated with inferior overall survival in such high-risk patients. We conducted single-center retrospective analysis of high-risk AA patients (N = 147) enrolled consecutively and undergoing matched related donor transplant from March 2002 through October 2018. We included high-risk AA patients receiving fludarabine (Flu)-based conditioning. Median patient age was 20 years (range, 3 to 52). The median time from diagnosis to transplant was 11 months (range, 3 to 63). High-risk features included age ≥ 20 years in 55.8% of patients (n = 82), disease duration more than 3 months in 95 % (n = 140), RBC concentrates transfusions > 20 in 79.6% (n = 117), random donor platelet transfusion > 50 in 64.6% of patients (n = 95), and second hematopoietic stem cell transplant (HSCT) in 7.4% (11). We divided patients into 2 groups based on different conditioning regimens. Flu group 1 (Flu1) received Flu 120 to 150 mg/m2, Cy 120 to 200 mg/kg, and ATG 20 mg/kg, and Flu group 2 (Flu2) was given Flu 150 mg/m2, Cy 300 mg/m2, and ATG 20 mg/kg. Bone marrow stem cells were used as graft source in 97% of patients (n = 144) (alone in 52% and with peripheral blood stem cells in 45%). Cyclosporine alone was used for GVHD prophylaxis in 75% (n = 110) and cyclosporine plus methotrexate in 25% (n = 37). Median total nucleated cell dose was 5 × 108/kg. Median days for neutrophil engraftment was 13 (range, 10 to 20) and platelet engraftment 20 (range, 14 to 43). Day 100 mortality was 7.5% (n = 11). Sustained successful engraftment was achieved in 87.8% of patients (n = 129). Most graft failures (40%) occurred in Flu2 conditioning (P = .000) and in patients with >2 risk factors (P = .000). Overall incidence of acute and chronic GVHD was 11.6% (n = 17) and 12.9% (n = 19), respectively, in Flu1 and Flu2 groups. Overall survival (OS), disease-free survival (DFS), and GVHD-free relapse-free survival (GRFS) was 83.7%, 78.2%, and 70.7%, respectively. A trend toward improved OS was observed in patients receiving Flu1 conditioning but was statistically nonsignificant (P = .256), whereas DFS and GRFS were significantly better in Flu1 versus Flu2 (P = .004 and .001, respectively). When stratified per number of risk factors (age > 20, RBC concentrate > 20 or platelet > 50 random, duration > 3 months, previous HSCT), OS and DFS decreased significantly with increasing number of risk factors (P = .000 and .001, respectively). Patients are able to tolerate Flu-based conditioning well with lower rates of rejection and excellent long-term survival in high-risk AA patients. Cyclosporine alone as GVHD prophylaxis and marrow source stem cells as graft source are preferable options. Use of Flu plus low-dose Cy conditioning is associated with inferior survival outcomes. A randomized trial of Flu-based versus conventional Cy-containing conditioning would be helpful in establishing a standard of care conditioning regimen in high-risk AA patients.