Ali Yar Khan - Academia.edu (original) (raw)

Papers by Ali Yar Khan

Digestive Diseases and Sciences

Administration of antibiotics in patients with cirrhosis and upper gastrointestinal bleeding has ... more Administration of antibiotics in patients with cirrhosis and upper gastrointestinal bleeding has been shown to improve outcomes. Little is known regarding optimum duration of prophylactic antibiotics. Seven days of antibiotics are generally recommended but very few studies have compared antibiotic duration to clinical outcomes in current available scientific literature. The goal of our study was to study the effect of shorter antibiotic duration on patient outcomes. We conducted a retrospective cohort study of patients with cirrhosis presenting with upper GI bleeding at our institute from 2010 to 2018. Patients were divided into three cohorts based on duration of antibiotic administration for prophylaxis: 1–3 days of antibiotics, 4–6 days of antibiotics and 7 days or more of antibiotics. Rates of infection diagnosis within 30 days, rebleeding, and mortality were compared between the three groups with Chi square, Fisher Exact and Kruskall–Wallace tests. Multivariable analysis was conducted to evaluate independent risk factors for infection. Medical charts of 980 patients with cirrhosis and upper GI bleeding during the study period were reviewed. A total of 303 with upper gastrointestinal bleeding were included in the final sample, of these 243 patients received antibiotics for prophylaxis and were included for analysis. Seventy-seven patients received antibiotic therapy for 3 days or less, 69 patients for 4–6 days, and 97 patients longer than 6 days. The three groups were well matched in demographic and clinical variables. Twenty-seven patients developed infections within 30 days of bleeding. MELD-Na score at presentation and presence of ascites were associated with infection within 30 days. Rates of infection were not statistically different between the three antibiotic groups (p = 0.78). In the thirty days following the GI bleed, pneumonia was the most diagnosed infection (eleven patients) followed by urinary tract infections (eight patients). Four patients developed spontaneous bacterial peritonitis and three were diagnosed with bacteremia. There was no difference in time to infection (Kruskall Wallace test p = 0.75), early re-bleeding (p = 0.81), late re-bleeding (p = 0.37) and in-hospital mortality (p = 0.94) in the three groups. Six patients in the cohort developed C. Difficile infection; no patient in the short antibiotic group developed C. Difficile infection. Short course of antibiotics for prophylaxis (3 days) appears safe and adequate for prophylaxis in patients with cirrhosis with upper gastrointestinal bleeding if there is no active infection.

Clinical Endoscopy

Background/Aims: There are few studies assessed the efficacy and mortality of endoscopic retrogra... more Background/Aims: There are few studies assessed the efficacy and mortality of endoscopic retrograde cholangiopancreatography (ERCP) for the removal of common bile duct (CBD) stones in the elderly aged ≥90 years. We aimed to assess the safety and efficacy of endoscopic removal of CBD stones in nonagenarians.Methods: We retrospectively reviewed ERCP reports for CBD stone removal. The endoscopic and therapeutic outcomes were collected. The length of stay (LOS), the total number of adverse events, and mortality rate were compared between groups.Results: A total of 125 nonagenarians were compared with 1,370 controls (65–89 years old individuals). The mean LOS for nonagenarians was significantly higher than in controls (13.6 days vs. 6.5 days). Completed intended treatment was similar in the nonagenarians and controls (89.8% and 89.5%, respectively). The overall complication rate did not differ between the groups. However, nonagenarians had a higher incidence of post-ERCP pneumonia (3.9%)...

Wireless Personal Communications

Information and Communication Technologies are regularly used in medical services and association... more Information and Communication Technologies are regularly used in medical services and associations around the world. An increasing number of devices running Android as Smartphones, smart TV and tablets, are comprehensively utilized for numerous purposes. For these devices, there are distinctive types of health and medical applications that provide an easy access to patients and their caretakers to save time [1]. In this work, we develop an Android application named Help Pro with an important goal: save lives by a single tap. In case of emergency, Help Pro users could have an ambulance available within 100 m of the user’s real-time location. Through the Dijkstra algorithm, this application employs Google Maps API (Application Programming Interface) to trace the nearest way in order to an available ambulance arrives on time. Consequently, not only time is efficiently saved but also precious lives.

International Journal for Research in Applied Science and Engineering Technology

Information Technology Service Management is the process to plan, implement, deliver and support ... more Information Technology Service Management is the process to plan, implement, deliver and support the IT services to cater the end-users' needs. This project aims to study the existing ITSM systems and implement an improved system aided with technologies like chat-bot and data visualization. To resolve IT issues using quality ticket system, we need a robust service management framework based on ITIL framework. The system works in three distinct steps: Reporting, Managing and Resolving an issue. The aim of an ITSM system restore the undisturbed flow of the everyday business process after resolving the ticket. The chatbot caters to the smaller needs of the users without having a need to create a ticket in the ITSM system. Data visualization can help the management team as well as the users to visually keep the track of the tickets.

Blood, 2020

Background: Amyloidosis is characterized by the deposition of misfolded lambda or kappa light cha... more Background: Amyloidosis is characterized by the deposition of misfolded lambda or kappa light chain (AL) proteins in tissue. It commonly affects the heart, which correlates with poor prognosis. Disease-modifying therapies aim to suppress the production of abnormal light chains. Daratumumab (Dara) use is associated with a reduction in light chain protein production. Dara is a human anti-CD38 monoclonal antibody approved for the treatment of newly diagnosed and Relapsed & Refractory Multiple Myeloma. AL amyloidosis plasma cells express CD38, and therefore, Dara is an attractive alternative in this setting. This review aims to assess the efficacy and safety of daratumumab in pre-treated AL amyloidosis patients. Methods: We conducted a comprehensive literature search in PubMed, Embase, Medline using MeSH terms and keywords "AL amyloidosis," "daratumumab", and "darzalex" to incorporate the studies published up to July 2020. We included studies assessing the ...

Blood, 2020

Background: Philadelphia negative myeloproliferative neoplasms (MPNs) include polycythemia vera (... more Background: Philadelphia negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF). MPNs can progress to accelerated and blast phase (MPN-AP/BP), defined by blast percentage of 10-19% and ≥20%, respectively, based on IWG-MRT. The therapeutic options, aside from allogeneic hematopoietic stem cell transplantation (Allo-HSCT), are limited. Hypomethylating agents (HMAs), including azacitidine (5-aza) and decitabine, are an effective treatment option for myelodysplastic syndrome and acute myeloid leukemia (AML). They have been used for older adults who are ineligible for intensive chemotherapy. Herein, we did a systematic review to evaluate the efficacy and toxicity of HMAs in MPN-AP/BP. Methods We comprehensively searched multiple databases (PubMed, google scholar, EMBASE, and clinicaltrials.gov), from the inception of the database until April 2020. We used MeSH terms and keywords related to azacitidine, deci...

Blood, 2020

Background: The JAK-STAT pathway is a vital signaling pathway for various cytokines and growth fa... more Background: The JAK-STAT pathway is a vital signaling pathway for various cytokines and growth factors. An abnormal upregulation of this pathway is seen in myeloproliferative disorders, especially the classic BCR-ABL negative myelofibrosis (MF). Janus kinase inhibitors (JAKi) have been evaluated in various clinical trials regarding their efficacy in improving the outcomes for MF patients. In this review, we looked at the reduction of splenomegaly and symptom improvement as markers for efficacy of JAKi. Methods: We did a comprehensive literature search, following PRISMA guidelines, on PubMed, Cochrane, clinicaltrials.gov and Embase databases. We used MeSH terms and related keywords for MF and JAKi, including generic and trade names. We screened 3261 articles and selected 23 trials for our study. Case reports, case series, meta-analysis, review articles, observational studies, phase I trials and studies not reporting spleen response were excluded. Spleen and symptom responses were use...

Open Forum Infectious Diseases, 2021

Background Antibiotics in patients with cirrhosis and upper gastrointestinal bleeding are shown t... more Background Antibiotics in patients with cirrhosis and upper gastrointestinal bleeding are shown to improve outcomes. Little is known regarding optimum duration of prophylactic antibiotics, with 7 days of therapy generally recommended. Antibiotic duration has not been compared to outcomes in current scientific literature. The goal of our study was to study the effect of shorter antibiotic duration on outcomes. Methods This was a retrospective cohort study of patients with cirrhosis presenting with upper GI bleeding at our institute from 2010-2018. Patients were divided into three cohorts based on duration of antibiotic administration: 1-3 days, 4-6 days, and 7 days or more. Rates of infection within 30 days, time to infection, rebleeding and mortality were compared between the three groups. Multivariable analysis was conducted to evaluate independent risk factors for infection. Results Medical charts of 943 patients with cirrhosis and upper GI bleed were reviewed. 303 patients did no...

Blood, 2020

Introduction Allogenic hematopoietic stem cell transplantation (Allo-HSCT) used for the treatment... more Introduction Allogenic hematopoietic stem cell transplantation (Allo-HSCT) used for the treatment of multiple hematological malignancies requires immunosuppression, that can lead to the reactivation of viruses like EBV, CMV, adenovirus (AdV). These viruses pose a life-threatening risk to an individual like Graft vs Host Disease (GVHD) and other virus-specific complications. Adoptive T cell therapy (ATC) is an approach to treat refractory post-Allo-HSCT transplant viral infections. The aim of this study is to assess the efficacy of various ATCs being developed against various viruses. Methods A systematic search on PubMed, Embase, Clinicaltrials.gov, and Web of Science was performed for adoptive immunotherapy in viral infections after stem cell transplantation from inception to May 28, 2020. Out of 604 studies, 13 phase I and II clinical trials were selected for the systematic review. Results A total of 13 studies were included of which two studies included data on the pediatric popu...

American Journal of Gastroenterology, 2020

American Journal of Gastroenterology, 2020

TP25. TP025 SARCOIDOSIS: DIAGNOSIS, PROGNOSIS, AND TREATMENT, 2021

Journal of Hematology, 2019

Ibrutinib has shown to have better efficacy than standard chemoimmunotherapy in del17 positive ch... more Ibrutinib has shown to have better efficacy than standard chemoimmunotherapy in del17 positive chronic lymphocytic leukemia (CLL) patients; however its role in del17 negative patients is less clear. We aim to evaluate the efficacy of ibrutinib-based regimens in CLL. Seven databases were searched in accordance with PRISMA statement guidelines using the following keywords: chronic lymphocytic leukemia, CLL, Bruton tyrosine kinase inhibitor, BTK inhibitor, ibrutinib, and PCI-32765. Data from only prospective clinical trials was included. In a phase 3 trial (n = 136), the overall response rate (ORR) with ibrutinib was 92% whereas 18% patients had a complete response (CR). Progression free survival (PFS) and overall survival (OS) at 2 years were 89% and 95% respectively. Phase 3 trial (n = 195) with single agent ibrutinib showed ORR of 63%. PFS at 6 months and OS at 12 months were 88% and 90% respectively. In a phase 2 trial of relapsed and/or refractory (R/R) or high risk treatment naive (TN) patients, combination of ibrutinib and rituximab (n = 104) achieved an ORR of 100% (CR 28%) as compared to ORR 98% (CR 21%) with ibrutinib monotherapy (n = 102) with no significant difference in PFS. Combination of ibrutinib and ublituximab (n = 64) had an ORR of 78% (CR 7%) in a phase 3 study. In del17p negative R/R patients, combination of bendamustine/rituximab (BR) and ibrutinib (n = 289) achieved an ORR of 83% (CR/CRi 10%) and the 18 month PFS was 79%. In a phase 2 trial treated with ibrutinib (n = 145), patients with del17p R/R disease achieved an ORR of 64% and the 24 month PFS and OS was 63% and 75% respectively. In TN del17p patients (n = 35), ORR was 97% (CR-0) and the 24 month PFS and OS were 82% and 84% respectively with single agent ibrutinib. Ibrutinib is the treatment of choice for patients with del17p mutation and has good efficacy in RR/TN patients without del17p mutation. Ibrutinib is being evaluated in combination with rituximab for del17p mutations. Future prospects include combination of ibrutinib with frontline chemotherapy and other novel agents for TN and RR del17p negative patients.

Cureus, 2020

Neurological complications after cardiac catheterization are rare. We report an unusual case of i... more Neurological complications after cardiac catheterization are rare. We report an unusual case of isolated third cranial nerve palsy in a 72-year-old male patient whose past medical history was significant for diabetes mellitus and coronary artery disease (CAD). He presented for elective cardiac catheterization for stable angina, which revealed multivessel CAD and no intervention was done. Two hours after the procedure, the patient suddenly started complaining of new-onset double vision in his left eye. Ophthalmologic exam revealed ptosis of the left eye lid, sluggish pupillary reflex and impaired adduction of the left eye along with exotropia of the left eye on primary gaze, all findings consistent with the left third nerve palsy. Rest of the neurological exam and neuroimaging (CT angiogram of head and MRI brain) were normal. Embolic phenomenon has been described as a possible mechanism in such patients leading to small vessel ischemic disease and cerebral microinfarction. Neuro-ophthalmologic complications after cardiac catheterization are rare but devastating for the patients. These should be recognized promptly, and patients should undergo neuroimaging to evaluate for any identifiable causes. These patients should be treated with aspirin and statin therapy and evaluated by ophthalmology for correction with prism lenses if symptoms persist.

Journal of Blood Medicine, 2020

The blood transfusion (BT) system in Pakistan is fragmented, demand-driven and depends on weakly ... more The blood transfusion (BT) system in Pakistan is fragmented, demand-driven and depends on weakly regulated transfusion practices. There is a considerable possibility that transfusion-transmissible infections (TTIs) are contributing to the current epidemic of hepatitis B virus (HBV) and hepatitis C virus (HCV) (affecting 7.4% of the general population) in the country. To study this issue, we conducted a systematic review to identify articles related to TTIs and transfusion safety in Pakistan from January 1, 2010 to January 31, 2020. A review of 33 articles met the final criteria for qualitative synthesis. Analysis of these studies showed a cumulative frequency of HBV 2.04%, HCV 2.44%, HIV 0.038%, syphilis 1.1% and malaria 0.11%. The frequency of coinfections among blood donors varied from 0.0099% to 0.35%. The highest number of coinfections were HCV and syphilis, followed by HCV and HBV infections. Syphilis and malaria were tested in only 38% and 46% of all the blood donations in one study. The rate of voluntary non-remunerated donations (VNRDs) was less than 13%, and male donors were 95% to 100% in these studies. There was a significant difference in the frequency of HBV and HCV in VNRDs (0.48%) as compared to replacement donors (RDs) (4.15%). In short, this review shows a high frequency of TTIs, especially HBV, HCV and syphilis in the blood donor population in Pakistan. There is a high dependency on RDs, minimal use of healthy voluntary blood donation practices, inadequate screening of high-risk donors, repeated collections of the blood from RDs, poor quality of screening methods and limited knowledge of donor health. Without standardized safe transfusion practices, there will be an ongoing increase in transmission of TTIs, especially HBV, HCV, syphilis, and HIV leading to a significant adverse public health impact.

Gastroenterology, 2019

3.552 patients with gastric precancerous conditions were diagnosed with sarcopenia. Both diabetes... more 3.552 patients with gastric precancerous conditions were diagnosed with sarcopenia. Both diabetes mellitus (DM) (OR = 5.152, P = 0.005) and sarcopenic obesity (OR = 4.139, P = 0.016) were independent predictive factors for gastric cancer. And smoking, alcohol, DM, hypertension, dyslipidemia, Helicobacter pylori, and sarcopenia were significantly associated with gastric precancerous conditions. Conclusion: Sarcopenia and sarcopenic obesity were significantly associated with gastric carcinogenesis. Thus, sarcopenia may be one of the risk factors for gastric carcinogenesis.

D16. INSIGHTS FROM CLINICAL STUDIES AND DATABASES IN PNEUMONIA, 2020

Blood, 2018

Introduction Bendamustine (B) and Melflufen (Mel) are Non-Food and Drug Administration (FDA) appr... more Introduction Bendamustine (B) and Melflufen (Mel) are Non-Food and Drug Administration (FDA) approved novel alkylators that exert their cytotoxic effects by cross-linking of DNA strands via alkylation, resulting in the inhibition of mitotic checkpoints leading to cell death. We report published literature on efficacy and safety of combination regimens of novel alkylators in patients (pts) with multiple myeloma. Methods We performed a comprehensive literature search on articles published after 2012 using following search engines (Pubmed, Embase, Cochrane, Web of Science and Clinical Trials.gov). We included both phase II, III studies and summarized our data using absolute values and percentages. Results Bendamustine: We included four phase II studies of B involving 217 pts. One hundred seventy-six pts had relapsed and refractory multiple myeloma (RRMM) while 41 pts had newly diagnosed multiple myeloma (NDMM). The overall response rate (ORR) was 71.75 % and 92% in RRMM and NDMM pts re...

Blood, 2018

Background: Multiple Myeloma (MM) remains incurable. Majority of the patients ultimately relapse ... more Background: Multiple Myeloma (MM) remains incurable. Majority of the patients ultimately relapse with a lower median event free survival after each successive line of therapy. For newly diagnosed MM patients, the median progression free survival (PFS) has improved drastically with the advent of novel agents. Aim of our review is to discuss median PFSnwith novel agents in the 2nd 3rd and 4th line of treatment in MM. Methods: A comprehensive literature search was done in accordance with the PRISMA guidelines from Jan 1st 2010 to May 30th 2018 using the following 4 databases: PubMed/ Medline, Elsevier/Embase, Wiley/Cochrane and clinicaltrials.gov. Inclusion criteria consisted of all prospective clinical trials that a) included patients with 1-3 prior lines of therapies b) received novel therapeutic agents as an intervention c) outcome was reported as median PFS. We excluded case series, retrospective/observational studies, systematic reviews/meta-analysis. We identified 4777 records th...

Blood, 2018

Introduction Drugs that target activating mutations of Janus Kinase 2 (JAK2) have been the backbo... more Introduction Drugs that target activating mutations of Janus Kinase 2 (JAK2) have been the backbone of myelofibrosis (MF) management. With recent advancements in our understanding of the underlying molecular mechanisms involved in myelofibrosis (MF) pathogenesis, numerous novel agents have been developed in the last decade. We have systematically reviewed the mechanisms of actions, efficacy and safety of these drugs. Methods A comprehensive literature research was performed using PubMed, Cochrane, EMBASE, Web of Science and Clinicaltrials.gov. We included all trials that were under development in phase I/II/III trials. Our search identified 1642 full-length manuscripts or abstracts with published results in the last decade were screened for relevant studies. Of these, 212 articles were finalized for our final analyses. Results Hedgehog inhibitors (saridegib, glasdegib and sonidegib) targets signaling membrane protein, smoothened. The combination of sonidegib + ruxulotinib (RUX) elic...

Digestive Diseases and Sciences

Administration of antibiotics in patients with cirrhosis and upper gastrointestinal bleeding has ... more Administration of antibiotics in patients with cirrhosis and upper gastrointestinal bleeding has been shown to improve outcomes. Little is known regarding optimum duration of prophylactic antibiotics. Seven days of antibiotics are generally recommended but very few studies have compared antibiotic duration to clinical outcomes in current available scientific literature. The goal of our study was to study the effect of shorter antibiotic duration on patient outcomes. We conducted a retrospective cohort study of patients with cirrhosis presenting with upper GI bleeding at our institute from 2010 to 2018. Patients were divided into three cohorts based on duration of antibiotic administration for prophylaxis: 1–3 days of antibiotics, 4–6 days of antibiotics and 7 days or more of antibiotics. Rates of infection diagnosis within 30 days, rebleeding, and mortality were compared between the three groups with Chi square, Fisher Exact and Kruskall–Wallace tests. Multivariable analysis was conducted to evaluate independent risk factors for infection. Medical charts of 980 patients with cirrhosis and upper GI bleeding during the study period were reviewed. A total of 303 with upper gastrointestinal bleeding were included in the final sample, of these 243 patients received antibiotics for prophylaxis and were included for analysis. Seventy-seven patients received antibiotic therapy for 3 days or less, 69 patients for 4–6 days, and 97 patients longer than 6 days. The three groups were well matched in demographic and clinical variables. Twenty-seven patients developed infections within 30 days of bleeding. MELD-Na score at presentation and presence of ascites were associated with infection within 30 days. Rates of infection were not statistically different between the three antibiotic groups (p = 0.78). In the thirty days following the GI bleed, pneumonia was the most diagnosed infection (eleven patients) followed by urinary tract infections (eight patients). Four patients developed spontaneous bacterial peritonitis and three were diagnosed with bacteremia. There was no difference in time to infection (Kruskall Wallace test p = 0.75), early re-bleeding (p = 0.81), late re-bleeding (p = 0.37) and in-hospital mortality (p = 0.94) in the three groups. Six patients in the cohort developed C. Difficile infection; no patient in the short antibiotic group developed C. Difficile infection. Short course of antibiotics for prophylaxis (3 days) appears safe and adequate for prophylaxis in patients with cirrhosis with upper gastrointestinal bleeding if there is no active infection.

Clinical Endoscopy

Background/Aims: There are few studies assessed the efficacy and mortality of endoscopic retrogra... more Background/Aims: There are few studies assessed the efficacy and mortality of endoscopic retrograde cholangiopancreatography (ERCP) for the removal of common bile duct (CBD) stones in the elderly aged ≥90 years. We aimed to assess the safety and efficacy of endoscopic removal of CBD stones in nonagenarians.Methods: We retrospectively reviewed ERCP reports for CBD stone removal. The endoscopic and therapeutic outcomes were collected. The length of stay (LOS), the total number of adverse events, and mortality rate were compared between groups.Results: A total of 125 nonagenarians were compared with 1,370 controls (65–89 years old individuals). The mean LOS for nonagenarians was significantly higher than in controls (13.6 days vs. 6.5 days). Completed intended treatment was similar in the nonagenarians and controls (89.8% and 89.5%, respectively). The overall complication rate did not differ between the groups. However, nonagenarians had a higher incidence of post-ERCP pneumonia (3.9%)...

Wireless Personal Communications

Information and Communication Technologies are regularly used in medical services and association... more Information and Communication Technologies are regularly used in medical services and associations around the world. An increasing number of devices running Android as Smartphones, smart TV and tablets, are comprehensively utilized for numerous purposes. For these devices, there are distinctive types of health and medical applications that provide an easy access to patients and their caretakers to save time [1]. In this work, we develop an Android application named Help Pro with an important goal: save lives by a single tap. In case of emergency, Help Pro users could have an ambulance available within 100 m of the user’s real-time location. Through the Dijkstra algorithm, this application employs Google Maps API (Application Programming Interface) to trace the nearest way in order to an available ambulance arrives on time. Consequently, not only time is efficiently saved but also precious lives.

International Journal for Research in Applied Science and Engineering Technology

Information Technology Service Management is the process to plan, implement, deliver and support ... more Information Technology Service Management is the process to plan, implement, deliver and support the IT services to cater the end-users' needs. This project aims to study the existing ITSM systems and implement an improved system aided with technologies like chat-bot and data visualization. To resolve IT issues using quality ticket system, we need a robust service management framework based on ITIL framework. The system works in three distinct steps: Reporting, Managing and Resolving an issue. The aim of an ITSM system restore the undisturbed flow of the everyday business process after resolving the ticket. The chatbot caters to the smaller needs of the users without having a need to create a ticket in the ITSM system. Data visualization can help the management team as well as the users to visually keep the track of the tickets.

Blood, 2020

Background: Amyloidosis is characterized by the deposition of misfolded lambda or kappa light cha... more Background: Amyloidosis is characterized by the deposition of misfolded lambda or kappa light chain (AL) proteins in tissue. It commonly affects the heart, which correlates with poor prognosis. Disease-modifying therapies aim to suppress the production of abnormal light chains. Daratumumab (Dara) use is associated with a reduction in light chain protein production. Dara is a human anti-CD38 monoclonal antibody approved for the treatment of newly diagnosed and Relapsed & Refractory Multiple Myeloma. AL amyloidosis plasma cells express CD38, and therefore, Dara is an attractive alternative in this setting. This review aims to assess the efficacy and safety of daratumumab in pre-treated AL amyloidosis patients. Methods: We conducted a comprehensive literature search in PubMed, Embase, Medline using MeSH terms and keywords "AL amyloidosis," "daratumumab", and "darzalex" to incorporate the studies published up to July 2020. We included studies assessing the ...

Blood, 2020

Background: Philadelphia negative myeloproliferative neoplasms (MPNs) include polycythemia vera (... more Background: Philadelphia negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF). MPNs can progress to accelerated and blast phase (MPN-AP/BP), defined by blast percentage of 10-19% and ≥20%, respectively, based on IWG-MRT. The therapeutic options, aside from allogeneic hematopoietic stem cell transplantation (Allo-HSCT), are limited. Hypomethylating agents (HMAs), including azacitidine (5-aza) and decitabine, are an effective treatment option for myelodysplastic syndrome and acute myeloid leukemia (AML). They have been used for older adults who are ineligible for intensive chemotherapy. Herein, we did a systematic review to evaluate the efficacy and toxicity of HMAs in MPN-AP/BP. Methods We comprehensively searched multiple databases (PubMed, google scholar, EMBASE, and clinicaltrials.gov), from the inception of the database until April 2020. We used MeSH terms and keywords related to azacitidine, deci...

Blood, 2020

Background: The JAK-STAT pathway is a vital signaling pathway for various cytokines and growth fa... more Background: The JAK-STAT pathway is a vital signaling pathway for various cytokines and growth factors. An abnormal upregulation of this pathway is seen in myeloproliferative disorders, especially the classic BCR-ABL negative myelofibrosis (MF). Janus kinase inhibitors (JAKi) have been evaluated in various clinical trials regarding their efficacy in improving the outcomes for MF patients. In this review, we looked at the reduction of splenomegaly and symptom improvement as markers for efficacy of JAKi. Methods: We did a comprehensive literature search, following PRISMA guidelines, on PubMed, Cochrane, clinicaltrials.gov and Embase databases. We used MeSH terms and related keywords for MF and JAKi, including generic and trade names. We screened 3261 articles and selected 23 trials for our study. Case reports, case series, meta-analysis, review articles, observational studies, phase I trials and studies not reporting spleen response were excluded. Spleen and symptom responses were use...

Open Forum Infectious Diseases, 2021

Background Antibiotics in patients with cirrhosis and upper gastrointestinal bleeding are shown t... more Background Antibiotics in patients with cirrhosis and upper gastrointestinal bleeding are shown to improve outcomes. Little is known regarding optimum duration of prophylactic antibiotics, with 7 days of therapy generally recommended. Antibiotic duration has not been compared to outcomes in current scientific literature. The goal of our study was to study the effect of shorter antibiotic duration on outcomes. Methods This was a retrospective cohort study of patients with cirrhosis presenting with upper GI bleeding at our institute from 2010-2018. Patients were divided into three cohorts based on duration of antibiotic administration: 1-3 days, 4-6 days, and 7 days or more. Rates of infection within 30 days, time to infection, rebleeding and mortality were compared between the three groups. Multivariable analysis was conducted to evaluate independent risk factors for infection. Results Medical charts of 943 patients with cirrhosis and upper GI bleed were reviewed. 303 patients did no...

Blood, 2020

Introduction Allogenic hematopoietic stem cell transplantation (Allo-HSCT) used for the treatment... more Introduction Allogenic hematopoietic stem cell transplantation (Allo-HSCT) used for the treatment of multiple hematological malignancies requires immunosuppression, that can lead to the reactivation of viruses like EBV, CMV, adenovirus (AdV). These viruses pose a life-threatening risk to an individual like Graft vs Host Disease (GVHD) and other virus-specific complications. Adoptive T cell therapy (ATC) is an approach to treat refractory post-Allo-HSCT transplant viral infections. The aim of this study is to assess the efficacy of various ATCs being developed against various viruses. Methods A systematic search on PubMed, Embase, Clinicaltrials.gov, and Web of Science was performed for adoptive immunotherapy in viral infections after stem cell transplantation from inception to May 28, 2020. Out of 604 studies, 13 phase I and II clinical trials were selected for the systematic review. Results A total of 13 studies were included of which two studies included data on the pediatric popu...

American Journal of Gastroenterology, 2020

American Journal of Gastroenterology, 2020

TP25. TP025 SARCOIDOSIS: DIAGNOSIS, PROGNOSIS, AND TREATMENT, 2021

Journal of Hematology, 2019

Ibrutinib has shown to have better efficacy than standard chemoimmunotherapy in del17 positive ch... more Ibrutinib has shown to have better efficacy than standard chemoimmunotherapy in del17 positive chronic lymphocytic leukemia (CLL) patients; however its role in del17 negative patients is less clear. We aim to evaluate the efficacy of ibrutinib-based regimens in CLL. Seven databases were searched in accordance with PRISMA statement guidelines using the following keywords: chronic lymphocytic leukemia, CLL, Bruton tyrosine kinase inhibitor, BTK inhibitor, ibrutinib, and PCI-32765. Data from only prospective clinical trials was included. In a phase 3 trial (n = 136), the overall response rate (ORR) with ibrutinib was 92% whereas 18% patients had a complete response (CR). Progression free survival (PFS) and overall survival (OS) at 2 years were 89% and 95% respectively. Phase 3 trial (n = 195) with single agent ibrutinib showed ORR of 63%. PFS at 6 months and OS at 12 months were 88% and 90% respectively. In a phase 2 trial of relapsed and/or refractory (R/R) or high risk treatment naive (TN) patients, combination of ibrutinib and rituximab (n = 104) achieved an ORR of 100% (CR 28%) as compared to ORR 98% (CR 21%) with ibrutinib monotherapy (n = 102) with no significant difference in PFS. Combination of ibrutinib and ublituximab (n = 64) had an ORR of 78% (CR 7%) in a phase 3 study. In del17p negative R/R patients, combination of bendamustine/rituximab (BR) and ibrutinib (n = 289) achieved an ORR of 83% (CR/CRi 10%) and the 18 month PFS was 79%. In a phase 2 trial treated with ibrutinib (n = 145), patients with del17p R/R disease achieved an ORR of 64% and the 24 month PFS and OS was 63% and 75% respectively. In TN del17p patients (n = 35), ORR was 97% (CR-0) and the 24 month PFS and OS were 82% and 84% respectively with single agent ibrutinib. Ibrutinib is the treatment of choice for patients with del17p mutation and has good efficacy in RR/TN patients without del17p mutation. Ibrutinib is being evaluated in combination with rituximab for del17p mutations. Future prospects include combination of ibrutinib with frontline chemotherapy and other novel agents for TN and RR del17p negative patients.

Cureus, 2020

Neurological complications after cardiac catheterization are rare. We report an unusual case of i... more Neurological complications after cardiac catheterization are rare. We report an unusual case of isolated third cranial nerve palsy in a 72-year-old male patient whose past medical history was significant for diabetes mellitus and coronary artery disease (CAD). He presented for elective cardiac catheterization for stable angina, which revealed multivessel CAD and no intervention was done. Two hours after the procedure, the patient suddenly started complaining of new-onset double vision in his left eye. Ophthalmologic exam revealed ptosis of the left eye lid, sluggish pupillary reflex and impaired adduction of the left eye along with exotropia of the left eye on primary gaze, all findings consistent with the left third nerve palsy. Rest of the neurological exam and neuroimaging (CT angiogram of head and MRI brain) were normal. Embolic phenomenon has been described as a possible mechanism in such patients leading to small vessel ischemic disease and cerebral microinfarction. Neuro-ophthalmologic complications after cardiac catheterization are rare but devastating for the patients. These should be recognized promptly, and patients should undergo neuroimaging to evaluate for any identifiable causes. These patients should be treated with aspirin and statin therapy and evaluated by ophthalmology for correction with prism lenses if symptoms persist.

Journal of Blood Medicine, 2020

The blood transfusion (BT) system in Pakistan is fragmented, demand-driven and depends on weakly ... more The blood transfusion (BT) system in Pakistan is fragmented, demand-driven and depends on weakly regulated transfusion practices. There is a considerable possibility that transfusion-transmissible infections (TTIs) are contributing to the current epidemic of hepatitis B virus (HBV) and hepatitis C virus (HCV) (affecting 7.4% of the general population) in the country. To study this issue, we conducted a systematic review to identify articles related to TTIs and transfusion safety in Pakistan from January 1, 2010 to January 31, 2020. A review of 33 articles met the final criteria for qualitative synthesis. Analysis of these studies showed a cumulative frequency of HBV 2.04%, HCV 2.44%, HIV 0.038%, syphilis 1.1% and malaria 0.11%. The frequency of coinfections among blood donors varied from 0.0099% to 0.35%. The highest number of coinfections were HCV and syphilis, followed by HCV and HBV infections. Syphilis and malaria were tested in only 38% and 46% of all the blood donations in one study. The rate of voluntary non-remunerated donations (VNRDs) was less than 13%, and male donors were 95% to 100% in these studies. There was a significant difference in the frequency of HBV and HCV in VNRDs (0.48%) as compared to replacement donors (RDs) (4.15%). In short, this review shows a high frequency of TTIs, especially HBV, HCV and syphilis in the blood donor population in Pakistan. There is a high dependency on RDs, minimal use of healthy voluntary blood donation practices, inadequate screening of high-risk donors, repeated collections of the blood from RDs, poor quality of screening methods and limited knowledge of donor health. Without standardized safe transfusion practices, there will be an ongoing increase in transmission of TTIs, especially HBV, HCV, syphilis, and HIV leading to a significant adverse public health impact.

Gastroenterology, 2019

3.552 patients with gastric precancerous conditions were diagnosed with sarcopenia. Both diabetes... more 3.552 patients with gastric precancerous conditions were diagnosed with sarcopenia. Both diabetes mellitus (DM) (OR = 5.152, P = 0.005) and sarcopenic obesity (OR = 4.139, P = 0.016) were independent predictive factors for gastric cancer. And smoking, alcohol, DM, hypertension, dyslipidemia, Helicobacter pylori, and sarcopenia were significantly associated with gastric precancerous conditions. Conclusion: Sarcopenia and sarcopenic obesity were significantly associated with gastric carcinogenesis. Thus, sarcopenia may be one of the risk factors for gastric carcinogenesis.

D16. INSIGHTS FROM CLINICAL STUDIES AND DATABASES IN PNEUMONIA, 2020

Blood, 2018

Introduction Bendamustine (B) and Melflufen (Mel) are Non-Food and Drug Administration (FDA) appr... more Introduction Bendamustine (B) and Melflufen (Mel) are Non-Food and Drug Administration (FDA) approved novel alkylators that exert their cytotoxic effects by cross-linking of DNA strands via alkylation, resulting in the inhibition of mitotic checkpoints leading to cell death. We report published literature on efficacy and safety of combination regimens of novel alkylators in patients (pts) with multiple myeloma. Methods We performed a comprehensive literature search on articles published after 2012 using following search engines (Pubmed, Embase, Cochrane, Web of Science and Clinical Trials.gov). We included both phase II, III studies and summarized our data using absolute values and percentages. Results Bendamustine: We included four phase II studies of B involving 217 pts. One hundred seventy-six pts had relapsed and refractory multiple myeloma (RRMM) while 41 pts had newly diagnosed multiple myeloma (NDMM). The overall response rate (ORR) was 71.75 % and 92% in RRMM and NDMM pts re...

Blood, 2018

Background: Multiple Myeloma (MM) remains incurable. Majority of the patients ultimately relapse ... more Background: Multiple Myeloma (MM) remains incurable. Majority of the patients ultimately relapse with a lower median event free survival after each successive line of therapy. For newly diagnosed MM patients, the median progression free survival (PFS) has improved drastically with the advent of novel agents. Aim of our review is to discuss median PFSnwith novel agents in the 2nd 3rd and 4th line of treatment in MM. Methods: A comprehensive literature search was done in accordance with the PRISMA guidelines from Jan 1st 2010 to May 30th 2018 using the following 4 databases: PubMed/ Medline, Elsevier/Embase, Wiley/Cochrane and clinicaltrials.gov. Inclusion criteria consisted of all prospective clinical trials that a) included patients with 1-3 prior lines of therapies b) received novel therapeutic agents as an intervention c) outcome was reported as median PFS. We excluded case series, retrospective/observational studies, systematic reviews/meta-analysis. We identified 4777 records th...

Blood, 2018

Introduction Drugs that target activating mutations of Janus Kinase 2 (JAK2) have been the backbo... more Introduction Drugs that target activating mutations of Janus Kinase 2 (JAK2) have been the backbone of myelofibrosis (MF) management. With recent advancements in our understanding of the underlying molecular mechanisms involved in myelofibrosis (MF) pathogenesis, numerous novel agents have been developed in the last decade. We have systematically reviewed the mechanisms of actions, efficacy and safety of these drugs. Methods A comprehensive literature research was performed using PubMed, Cochrane, EMBASE, Web of Science and Clinicaltrials.gov. We included all trials that were under development in phase I/II/III trials. Our search identified 1642 full-length manuscripts or abstracts with published results in the last decade were screened for relevant studies. Of these, 212 articles were finalized for our final analyses. Results Hedgehog inhibitors (saridegib, glasdegib and sonidegib) targets signaling membrane protein, smoothened. The combination of sonidegib + ruxulotinib (RUX) elic...