Correlation of Cerebrospinal Fluid Total Protein and Serum Neutrophil-to-Lymphocyte Ratio with Clinical Outcomes of Guillain-Barre Syndrome Variants.

OBJECTIVE: To evaluate the correlation of cerebrospinal fluid total protein and serum neutrophil-to-lymphocyte ratio with the clinical outcomes and the various clinical and electrophysiological variants of Guillain-Barre syndrome. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: Department of Neurology, Mayo Hospital and King Edward Medical University, Lahore, Pakistan, from November 2022 to April 2023. METHODOLOGY: Fourty-six Guillain-Barre syndrome patients, aged 12-70 years, were included in the study diagnosed by using the Brighton's criteria. Functional disability and respiratory insufficiency were assessed by using the modified Hughes disability score and the Erasmus Guillain-Barre syndrome respiratory insufficiency score, respectively. Serum neutrophil-to-lymphocyte ratio and cerebrospinal fluid total protein were calculated for each patient at the time of admission. RESULTS: Axonal variants had a higher mean neutrophil-to-lymphocyte ratio (5.29 ± 4.38) than demyelinating variants (4.71 ± 3.4) and Miller-Fischer syndrome (3 ± 2.828). This ratio was positively correlated with the modified Hughes's disability score (r = 0.790, p = 0.001) and the Erasmus Guillain-Barre syndrome respiratory insufficiency score (r = 0.936, p = 0.002). Mean cerebrospinal fluid total protein was higher for demyelinating (218 ± 136 mg/dl) than axonal variants (86 ± 56 mg/dl) and Miller-Fischer syndrome (34 ± 21 mg/dl). However, higher modified Hughes disability score (4-6) (r = 0.020, p = 0.117) and a high Erasmus Guillain-Barre syndrome respiratory insufficiency score (5-7) (r = 0.115, p = 0.302) did not significantly affect mean cerebrospinal fluid total proteins. CONCLUSION: Serum neutrophil-to-lymphocyte ratio can be regarded as a reliable biomarker to assess disease severity and clinical outcome in Guillain-Barre syndrome. Cerebrospinal fluid total protein is a poor predictor of the prognosis and severity of Guillain-Barre syndrome. KEY WORDS: Guillain-Barre syndrome (GBS), Clinical outcome, Cerebrospinal fluid total protein (CSF-TP), Neutrophil-to-lymphocytic ratio (NLR), Prognostic biomarker.

Sarcopenia is a risk factor for post-transjugular intrahepatic portosystemic shunt hepatic encephalopathy and mortality: A systematic review and meta-analysis.

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is a commonly performed procedure in patients with liver cirrhosis to treat portal hypertension-related conditions, including variceal bleeding and refractory ascites. However, while the increased risk of hepatic encephalopathy (HE) after TIPS is important to consider when determining whether a patient is a good candidate for TIPS, currently there is no widely used method to predict the development of post-TIPS HE, although the model for end-stage liver disease (MELD) score is used to predict post-TIPS mortality. We conducted a systematic review and meta-analysis to evaluate sarcopenia as a risk factor for HE and mortality in patients undergoing TIPS. METHODS: A comprehensive search strategy was used to identify reports of post-TIPS HE and mortality in sarcopenia vs. non-sarcopenia patients with liver cirrhosis who received TIPS in March 2023. Open Meta Analyst was used to compute the results. RESULTS: Twelve studies with 2056 patients met inclusion criteria and were included in the final meta-analysis. Sarcopenia was associated with a significantly higher post-TIPS HE rate than non-sarcopenia (risk ratio [RR]: 1.68, 95% CI: 1.48-1.92, p < 0.00001, I2 = 65%), as well as a significantly higher post-TIPS mortality rate (RR: 1.73, 95% CI: 1.14-2.64, p < 0.00001, I2 = 87%). CONCLUSION: Patients with sarcopenia have a significantly increased risk of post-TIPS HE and mortality. Presence of sarcopenia should be considered when weighing the risks and benefits of performing TIPS in patients with cirrhosis. Further studies are needed to determine the clinical utility of important risk factors such as sarcopenia on post-TIPS outcomes.

Probiotics for the prevention and treatment of COVID-19: a rapid systematic review and meta-analysis.

Background: Although numerous modalities are currently in use for the treatment and prophylaxis of COVID-19, probiotics are a cost-effective alternative that could be used in diverse clinical settings. Hence, we conducted a meta-analysis to investigate the role of probiotics in preventing and treating COVID-19 infection. Methods: We searched several databases from inception to 30 May 2023 for all randomized controlled trials (RCTs) and comparative observational studies that evaluated probiotics (irrespective of the regimen) for the treatment or prevention of COVID-19. We conducted our meta-analysis using RevMan 5.4 with risk ratio (RR) and mean difference (MD) as the effect measures. Results: A total of 18 studies (11 RCTs and 7 observational studies) were included in our review. Probiotics reduced the risk of mortality (RR 0.40; 95% CI: 0.25-0.65, I2 = 0%). Probiotics also decreased the length of hospital stay, rate of no recovery, and time to recovery. However, probiotics had no effect on the rates of ICU admission. When used prophylactically, probiotics did not decrease the incidence of COVID-19 cases (RR 0.65; 95% CI: 0.37-1.12; I2 = 66%). The results for all outcomes were consistent across the subgroups of RCTs and observational studies (P for interaction >0.05). Conclusion: The results of this meta-analysis support the use of probiotics as an adjunct treatment for reducing the risk of mortality or improving other clinical outcomes in patients with COVID-19. However, probiotics are not useful as a prophylactic measure against COVID-19. Large-scale RCTs are still warranted for determining the most efficacious and safe probiotic strains. Systematic Review Registration: PROSPERO (CRD42023390275: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=390275).

Brait-Fahn-Schwartz Disease: A Unique Co-Occurrence of Parkinson's Disease and Amyotrophic Lateral Sclerosis.

The Parkinson's disease-amyotrophic lateral sclerosis (ALS) complex typically manifests as levodopa-responsive parkinsonism, followed by ALS. It is extremely rare for Parkinson's disease and ALS to coexist without other neurological disorders. Named after the scientists who first described this overlap of two neurodegenerative conditions, it is referred to as Brait-Fahn-Schwartz disease. Given its variable presentation, increasing rarity, and lack of any diagnostic test, it poses a diagnostic challenge for physicians. We present a case of a 55-year-old Pakistani male experiencing progressive quadriparesis with spastic lower limbs and flaccid upper limbs, in addition to the cardinal features of idiopathic Parkinson's disease. Since there is currently no cure available for either Parkinson's disease or ALS, all available treatment focuses on improving quality of life, which we achieved in our patient. This case is unique in being the first incidence of Parkinson's disease-ALS complex in a novel geographic region such as Pakistan, where genetic testing and cost constraints limit the diagnosis of rare disorders. The coexistence of extrapyramidal symptoms and pyramidal symptoms is uncommon. In such situations, physicians may overlook one group of symptoms, potentially leading to a misdiagnosis. This case highlights the value of a thorough physical examination and electrodiagnostic studies and suggests the association between Parkinson's disease and ALS. This case demonstrates the significance of understanding when Parkinson's disease symptoms start to appear in patients with ALS and the need to start dopaminergic therapy in those who had Parkinson's disease features before ALS to alleviate the suffering of an individual and enhance quality of life.

Prevalence of Fibromyalgia and Chronic Fatigue Syndrome among Individuals with Irritable Bowel Syndrome: An Analysis of United States National Inpatient Sample Database.

Background and Aim: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with other somatic disorders. We studied the prevalence and predictors of fibromyalgia and chronic fatigue syndrome (CFS) in IBS patients. Methods: We used the National Inpatient Sample and included hospitalization of individuals with IBS, using ICD-10 codes, from 2016-2019. The prevalence and predictors of fibromyalgia and CFS in IBS patients were studied. Univariate and multivariate patient- and hospital-level regression models were used to calculate the adjusted odds of fibromyalgia and CFS in the IBS patient population. Results: Of 1,256,325 patients with an ICD-10 code of IBS included in the study, 10.73% (134,890) also had ICD-10 codes for fibromyalgia and 0.42% (5220) for CFS. The prevalence of fibromyalgia and CFS was significantly higher in IBS patients (adjusted odds ratio (AOR) 5.33, 95% confidence interval (CI) 5.24-5.41, p < 0.001, and AOR 5.40, 95% CI 5.04-5.78, p < 0.001, respectively) compared to the general adult population without IBS. IBS-diarrhea, IBS-constipation, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS. Increasing age (AOR 1.02, 95% CI 1.01-1.04, p 0.003; AOR 1.02, 95% CI 1.01-1.03, p 0.001), female gender (AOR 11.2, 95% CI 11.1-11.4, p < 0.001; AOR 1.86, 95% CI 1.78-1.93, p < 0.001) and white race (AOR 2.04, 95% CI 1.95-2.12, p < 0.001; AOR 1.69, 95% CI 1.34-2.13, p < 0.001) were independent predictors of increased odds of fibromyalgia and CFS, respectively. Conclusions: It appears that IBS is associated with an increased prevalence of somatic disorders such as fibromyalgia and CFS.

Comparative assessment of SARS CoV2-associated mortalities in 3 COVID waves and related risk factors: The South Kashmir's experience.

Introduction: Severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) pandemic have spurted in three major waves in India at different times and had different levels of severity in different waves. The objective of our study was to determine the comparative mortality rate in three COVID-19 waves and determine the factors associated with mortality. Methods: We identified a cohort of 1,132 COVID-19 patients who were admitted between April 14, 2020 and February 08, 2022 at our center. All the admitted patients with positive COVID-polymerase chain reaction were included in the study. Sample characteristics were determined by screening age, sex, socio-economic status, occupation, symptomatology of COVID, patient status on admission, baseline investigations, comorbidities, medical history, oxygen dosage needed during admission, the span of hospital stay, diagnosis, and vitals such as blood pressure, pulse, and oxygen saturation. All the data were procured from an institutional database. Results: In total, 1,132 patients included in the study, the mean age was 65.08 ± 12.29 and 56% were males. The affliction rate was 42.13% in >60 years, 29.5% in 46-60 years, 20.8% in 31-45 years, and 7.4% in 30 years' group. In the first, second, and third waves of COVID-19, the mortality rates were 13.21%, 23.53%, and 11.39%, respectively. Among the comorbidities, mortality rates were proportionately higher in those with hypertension (6.7%), and diabetes (5.5%), than those with chronic obstructive pulmonary disease (3.3%), chronic kidney disease (CKD) (1.5%), heart disease (1.6%), and malignancy (0.2%). Conclusion: We identify the peaked mortalities in the second encounter which was predicted by age, comorbidities such as hypertension, and diabetes.

Fahr's syndrome as a manifestation of autoimmune polyendocrine syndrome-1 and its unusual association with neuromyelitis optica spectrum disorder.

Fahr's syndrome, also known as bilateral striopallidodendate calcinosis, is a rare inherited neurodegenerative illness characterized by abnormal calcium deposition in several areas of the brain, resulting in a wide range of neuropsychological symptoms. Fahr's syndrome, secondary to autoimmune polyendocrine syndrome type 1, which includes adrenal insufficiency and mucocutaneous candidiasis in addition to hypoparathyroidism, is exceedingly rare. No case report has been documented to date to show the co-occurrence of Fahr's syndrome and neuromyelitis optica spectrum disorder. Here, we discuss the case of a 30-year-old man with a previous history of seizures and symptoms of ectodermal dystrophy presented with seizures, left-sided hemiparesis, dysarthria, and other characteristics indicative of severe hypocalcemia. The neuroimaging findings strongly suggested Fahr's syndrome, with radiographic evidence of Neuromyelitis optica spectrum disorder as longitudinal extensive transverse myelitis in the cervical spinal cord, high titers of serum aquaporin-4 antibodies, and demyelinating neuropathy on nerve conduction studies. This distinct neuropsychological presentation and neuroimaging findings led to the diagnosis of Fahr's syndrome as a result of hypoparathyroidism caused by autoimmune polyendocrine syndrome type 1 with cooccurrence of neuromyelitis optica spectrum disorder. The patient's clinical symptoms improved considerably after he was treated based on a provisional diagnosis. The clinical importance of our case is significant for both neuropsychiatrists and endocrinologists, as autoimmune polyendocrine syndrome should be considered as the etiology of Fahr's syndrome. This case report also aims to report this unusual association of Neuromyelitis optica spectrum disorder with Fahr's syndrome to give the future prospective to know whether this association is incidental or there is a missing link between these two different disorders.

Nanobiotechnology in crop stress management: an overview of novel applications.

Agricultural crops are subject to a variety of biotic and abiotic stresses that adversely affect growth and reduce the yield of crop plantss. Traditional crop stress management approaches are not capable of fulfilling the food demand of the human population which is projected to reach 10 billion by 2050. Nanobiotechnology is the application of nanotechnology in biological fields and has emerged as a sustainable approach to enhancing agricultural productivity by alleviating various plant stresses. This article reviews innovations in nanobiotechnology and its role in promoting plant growth and enhancing plant resistance/tolerance against biotic and abiotic stresses and the underlying mechanisms. Nanoparticles, synthesized through various approaches (physical, chemical and biological), induce plant resistance against these stresses by strengthening the physical barriers, improving plant photosynthesis and activating plant defense mechanisms. The nanoparticles can also upregulate the expression of stress-related genes by increasing anti-stress compounds and activating the expression of defense-related genes. The unique physico-chemical characteristics of nanoparticles enhance biochemical activity and effectiveness to cause diverse impacts on plants. Molecular mechanisms of nanobiotechnology-induced tolerance to abiotic and biotic stresses have also been highlighted. Further research is needed on efficient synthesis methods, optimization of nanoparticle dosages, application techniques and integration with other technologies, and a better understanding of their fate in agricultural systems.

From COVID to conflict: Understanding the deriving forces of environment and implications for natural resources.

In the contemporary world, the importance of natural resources is increasing day by day especially due to extraordinary circumstances, i.e., COVID-19 and global conflicts. The abundance of natural resource is considered competitive advantage and crucial for sustainable development. However, the role of natural resources can be questionable especially if its impact on the economy is negative. Sustainable use of natural resources is currently the biggest challenge for governance. Following these footprints, the study aims to revisit a novel perspective of natural resources in the context of global conflicts using data from Asian economies for the period of 1996-2020. In this pursuit, this study investigates how governance balances macroeconomic variables with sustainable development to account for effective climate change adaptation, mitigation efforts and integral to control conflicts. The second-generation test of CIPS and CADF are used to deal with cross-sectional dependence issues and Westerlund cointegration to estimate long-run relationships. Furthermore, the long-run coefficients are estimated by the PMG estimator using dynamic panel ARDL approach. The findings confirm that surpassing the threshold level of governance is essential to promote environmental quality and preservation of natural resources. The region needs to promote steward policy for resources. This can take the form of nationalizing resource assets, increasing taxes and royalties on resource extraction to ensure sustainable development. The handlers need to design polices supportive to renewable energy consumption, endorse IT based industry solution, encourage high-tech inward FDI, promote green financing and support sustainable development.

Comparative Efficacy of Treatment Options for the Prevention of Post-TIPS Hepatic Encephalopathy: A Systematic Review and Network Meta-analysis.

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is often used in patients with cirrhosis to manage portal hypertension-related complications. Unfortunately, 35-50% of patients develop overt hepatic encephalopathy (HE) after TIPS. However, data on lactulose and rifaximin to prevent post-TIPS HE is limited. Therefore, we aimed to perform a network meta-analysis to investigate the efficacy of multiple pharmacological regimens in the prevention of post-TIPS HE. METHODS: A comprehensive search strategy to identify reports of studies of rifaximin use on post-TIPS hepatic encephalopathy was constructed using truncated keywords, phrases, and subject headings developed in Embase. This strategy was translated to MEDLINE, Cochrane Central Register of Controlled Trials, and the Web of Science Core Collection, with all searches performed on 10 February 2022. No publication date or language limits were used. RESULTS: The initial search identified 72 studies, and 56 studies were screened after removing duplicates. Five studies, two randomized controlled trials (RCTs) and three retrospective studies, met our inclusion criteria and were included in the final analysis. A total of 840 patients were included, with 65% male. Our meta- analysis did not find a statistically significant difference between lactulose vs placebo/no prophylaxis, nor rifaximin vs placebo/no prophylaxis, nor rifaximin plus lactulose vs placebo/no prophylaxis in the reduction of post-TIPS HE. CONCLUSIONS: Rifaximin alone, lactulose alone, and rifaximin plus lactulose did not significantly reduce the development of post-TIPS HE. Based on the P-scores of the three treatment groups, the combination of rifaximin plus lactulose showed the most promising trend towards preventing post-TIPS HE. More studies, especially large RCTs, are warranted.

Idiopathic myointimal hyperplasia of the mesenteric veins: A systematic review and individual patient data regression analysis.

BACKGROUND AND AIM: Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) is an uncommon cause of colonic ischemia for which surgical treatment is typically curative. We describe clinical, radiologic, and endoscopic findings in IMHMV patients to provide clinicians with a framework for pre-surgical identification of this rare disease. METHODS: We performed a systematic review of seven databases for IMHMV cases and identified additional cases from Yale New Haven Hospital records. To identify features specifically associated with colonic ischemia due to IMHMV, we performed multivariate logistic regression analysis incorporating data from a large cohort of patients with biopsy-proven ischemic colitis. RESULTS: A total of 124 patients with IMHMV were identified (80% male, mean age 53 years, 56% Caucasian). Presenting symptoms were most commonly abdominal pain (86%) and diarrhea (68%). The most affected areas were the sigmoid colon (91%) and rectum (61%). Complications associated with diagnostic delay occurred in 29% of patients. Radiologic vascular abnormalities including non-opacification of the inferior mesenteric vein were observed in 35% of patients. Of the patients, 97% underwent curative surgical resection. Compared with non-IMHMV colonic ischemia, IMHMV was significantly associated with younger age, male sex, absence of rectal bleeding on presentation, rectal involvement, and mucosal ulcerations on endoscopy. CONCLUSION: IMHMV is a rare, underreported cause of colonic ischemia that predominantly involves the rectosigmoid. Our findings suggest younger age, rectal involvement, and absence of rectal bleeding as clinical features to help identify select patients presenting with colonic ischemia as having higher likelihood of IMHMV and therefore consideration of upfront surgical management.

A novel pseudo-multicomponent isoconversional approach for the estimation of kinetic and thermodynamic parameters of potato stalk thermal degradation.

This study examined the thermal degradation kinetics of potato stalk (PS) using a unique isoconversional technique. The kinetic analysis was assessed based on mathematical deconvolution approach with model-free method. The thermogravimetric analyzer (TGA) was used for the non-isothermal pyrolysis of PS at different heating rates. The Gaussian function was then used to extract three pseudo-components (PC) from the TGA findings. The average activation energy value for PS (125.99, 122.79, and 122.85 kJ/mol), PC1 (106.78, 103.83, and 103.92 kJ/mol), PC2 (120.26, 116.31, and 116.55 kJ/mol), and PC3 (373.12, 379.40, and 378.93 kJ/mol) based on OFW, KAS, and VZN model respectively. Furthermore, an artificial neural network (ANN) was used to forecast the thermal degradation data. The findings demonstrated a significant correlation between real and anticipated values. The kinetic and thermodynamic results, along with ANN are critical for constructing pyrolysis reactors that might use waste biomass as a potential feedstock for bioenergy production.

Role of rifaximin in the management of alcohol-associated hepatitis: A systematic review and meta-analysis.

BACKGROUND AND AIM: Alcohol-associated hepatitis (AAH) is an acute, inflammatory liver disease with severe short-term and long-term morbidity and mortality. AAH can lead to severe complications including hepatic failure, gastrointestinal bleeding, sepsis, and the development or decompensation of cirrhosis. Rifaximin is an antibiotic that reduces bacterial overgrowth and gut translocation, and it may have a role in decreasing systemic inflammation and infection in patients with AAH. Therefore, we conducted a systematic review and meta-analysis to evaluate the role of rifaximin in the management of AAH. METHODS: A comprehensive search strategy was used to identify studies that met our inclusion criteria in Embase, MEDLINE (PubMed), Cochrane Library, Web of Science Core Collection, and Google Scholar. Outcomes of interest included rates of infection, 90-day mortality, and overall mortality between the rifaximin versus non-rifaximin group. Open Meta Analyst software was used to compute the results. RESULTS: Three studies with a total of 162 patients were included in the final meta-analysis. Of the three studies, two were randomized control trials (RCTs), and one was a case-control study. There was a significantly lower rate of infection in the rifaximin group versus the non-rifaximin group (RR: 0.331, 95% CI: 0.159-0.689, I2  = 0%, P = 0.003). There was no significant difference in 90-day mortality in the rifaximin versus non-rifaximin group (RR: 0.743, 95% CI: 0.298-1.850, I2  = 24%, P = 0.523), nor was there a significant difference in overall mortality (RR: 0.624, 95% 95% CI: 0.299-1.3, I2  = 7.1%, P = 0.208). CONCLUSIONS: The use of rifaximin in AAH is associated with a lower rate of infection rate than the non-rifaximin group. Additional research is needed to determine whether this effect is more pronounced in patients concurrently being treated with prednisolone. Differences in 90-day or overall mortality did not reach statistical significance. Further studies, particularly large randomized controlled trials, are needed to establish the role of rifaximin in AAH, especially as an adjunct therapy with prednisolone.

Trans Oral Endoscopic Thyroidectomy Vestibular Approach (Toetva), Case Series Of The First Clinical Experience From Pakistan.

BACKGROUND: The objective of the study to assess the workability and cosmetic outcome of endoscopic thyroidectomy vestibular approach (TOETVA) and share results of underdeveloped country with the world about their first clinical experience. METHODS: We performed TOETVA in 3 patients presenting with thyroid nodules in our hospital, between October 2020 and December 2020 at Liaquat National hospital. Three-port technique was used, one 10-mm port for camera and two 5-mm ports for working. All ports were passed through oral vestibule. The demographic data of the patients and surgical outcomes were retrospectively reviewed. The surgery was completed successfully in all 3 patients. The operative time was between 120-150 mins. RESULTS: No complications such as recurrent laryngeal nerve palsy, mental nerve injury or parathyroid gland injury damage occurred in patients postoperatively. No visible scarring occurred in the patients postoperatively. Patients remain stable after surgery and got discharged next day. No complications were noted in 6 months follow up. CONCLUSIONS: TOETVA is safe, feasible, and effective and scar free option as compared to conventional thyroid surgery.

Image-based cell sorting using focused travelling surface acoustic waves.

Sorting cells is an essential primary step in many biological and clinical applications such as high-throughput drug screening, cancer research and cell transplantation. Cell sorting based on their mechanical properties has long been considered as a promising label-free biomarker that could revolutionize the isolation of cells from heterogeneous populations. Recent advances in microfluidic image-based cell analysis combined with subsequent label-free sorting by on-chip actuators demonstrated the possibility of sorting cells based on their physical properties. However, the high purity of sorting is achieved at the expense of a sorting rate that lags behind the analysis throughput. Furthermore, stable and reliable system operation is an important feature in enabling the sorting of small cell fractions from a concentrated heterogeneous population. Here, we present a label-free cell sorting method, based on the use of focused travelling surface acoustic wave (FTSAW) in combination with real-time deformability cytometry (RT-DC). We demonstrate the flexibility and applicability of the method by sorting distinct blood cell types, cell lines and particles based on different physical parameters. Finally, we present a new strategy to sort cells based on their mechanical properties. Our system enables the sorting of up to 400 particles per s. Sorting is therefore possible at high cell concentrations (up to 36 million per ml) while retaining high purity (>92%) for cells with diverse sizes and mechanical properties moving in a highly viscous buffer. Sorting of small cell fraction from a heterogeneous population prepared by processing of small sample volume (10 µl) is also possible and here demonstrated by the 667-fold enrichment of white blood cells (WBCs) from raw diluted whole blood in a continuous 10-hour sorting experiment. The real-time analysis of multiple parameters together with the high sensitivity and high-throughput of our method thus enables new biological and therapeutic applications in the future.

Hepatitis C prevalence and elimination planning in Pakistan, a bottom-up approach accounting for provincial variation.

In Pakistan, substantial changes to hepatitis C virus (HCV) programming and treatment have occurred since the 2008 nationwide serosurvey estimated a 4.8% anti-HCV prevalence. In the absence of an updated national study, this analysis uses provincial data to estimate a national prevalence and the interventions needed to achieve elimination. Using a Delphi process, epidemiologic HCV data for the four provinces of Pakistan (accounting for 97% of the population) were reviewed with 21 subject-matter experts in Pakistan. Province-level estimates were inputted into a mathematical model to estimate the national HCV disease burden in the absence of intervention (Base), and if the World Health Organization (WHO) elimination targets are achieved by 2030 (80% reduction in new infections, 90% diagnosis coverage, 80% treatment coverage, and 65% reduction in mortality: WHO Elimination). An estimated 9,746,000 (7,573,000-10,006,000) Pakistanis were living with viraemic HCV as of January 1, 2021; a viraemic prevalence of 4.3% (3.3-4.4). WHO Elimination would require an annual average of 18.8 million screens, 1.1 million treatments, and 46,700 new infections prevented anually between 2022 and 2030. Elimination would reduce total infections by 7,045,000, save 152,000 lives and prevent 104,000 incident cases of hepatocellular carcinoma from 2015 to 2030. Blood surveys, programmatic data, and expert panel input uncovered more HCV infections and lower treatment numbers in the provinces than estimated using national extrapolations, demonstrating the benefits of a bottom-up approach. Screening and treatment must increase 20 times and 5 times, respectively, to curb the HCV epidemic in Pakistan and achieve elimination by 2030.

Impact of thiopurine dose in anti-tumor necrosis factor combination therapy on outcomes in inflammatory bowel disease.

Background: Combination therapy with thiopurines and anti-tumor necrosis factor (TNF) is superior to monotherapy in Crohn's disease (CD) and ulcerative colitis (UC). The optimal dose of thiopurines in combination therapy remains unclear. We investigated the impact of thiopurine dose in combination therapy on outcomes in inflammatory bowel disease (IBD). Methods: This was a single-center, retrospective study of patients with IBD treated with thiopurine and anti-TNF combination therapy between 1/2012 and 11/2020. A therapeutic dose of thiopurines was defined as ≥1 mg/kg for 6-mercaptopurine and ≥2 mg/kg for azathioprine. The primary outcome was anti-drug antibody (ADA) formation in patients on a therapeutic thiopurine dose vs. a lower thiopurine dose group. Secondary outcomes included steroid-free clinical remission, endoscopic healing (absence of ulcers/erosions in CD and Mayo endoscopic score ≤1 for UC), and normal serum C-reactive protein (CRP) in patients who were on combination therapy. Results: A total of 108 patients were included (median age 31.5 years; 58.3% male). A therapeutic dose of thiopurine was used in 19%. In the therapeutic thiopurine dose group, 23.8% developed ADA vs. 29.9% (P=0.58) in the lower dose group. No significant differences were noted between the therapeutic and lower dose thiopurine groups in terms of steroid-free clinical remission (57.1% vs. 60.9%, P=0.75), endoscopic healing (55% vs. 60%, P=0.69), and normal CRP (52.4% vs. 52.9%, P=0.27). Conclusion: In our cohort of patients with IBD on anti-TNF combination therapy, thiopurine dose was not associated with significant differences in anti-TNF immunogenicity and clinical outcomes.