Clinical Research in Chronic Lymphocytic Leukemia in Pakistan; A Systematic Review.

Background: Significant advances have been made in the treatment of chronic lymphocytic leukemia (CLL) since the turn of the new millennium. However, most clinical trials were done in developed countries where minority ethnicities were underrepresented. Materials and Methods: To gauge the quality of research in CLL being done in Pakistan, we conducted a comprehensive literature search using PubMed, Clinicaltrials.gov, and Google Scholar on 14 January 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Results: A total of 16 studies met the inclusion criteria. The most common study design was cross-sectional. Eight studies evaluated the clinicohematological profile of CLL patients and the effect of various cytogenic abnormalities through fluorescence in situ hybridization (FISH) technique on disease progression and prognosis. Five studies discussed the prevalence of abnormalities such as autoimmune cytopenias and other serum chemistry derangements. Only two studies evaluated treatment outcomes, among which one study reported a 2-year overall survival of 65% among patients with 17p deletion. None of the studies had patients on novel targeted agents. No pharmaceutical sponsored or funded clinical trials were found. Conclusions: Our review suggests that although small clinical studies continue to be performed across the country, multiple financial and logistical barriers need to be addressed for larger, more impactful clinical trials to be conducted that will help answer demographic-specific questions and decrease reliance on foreign studies.

Poor hospitalization outcomes in patients undergoing allogeneic hematopoietic stem cell transplant with hospital acquired influenza infection.

INTRODUCTION: Although hospital-acquired influenza infection (HAII) is a known complication among immunocompromised patients, the data in the setting of hospitalization for allogeneic hematopoietic stem cell transplant (allo-HSCT) are scarce. METHODS: A retrospective study using the National Inpatient sample database was done to determine the impact of HAII on hospitalization outcomes among patients admitted for allo-HSCT. RESULTS: The data for 77 103 allo-HSCT weighted hospitalizations were collected between 2002 and 2019. Among these, only 314 (0.4%) allo-HSCT cases were billed for HAII. Patients with influenza were more likely to have comorbid conditions like chronic obstructive lung disease, diabetes mellitus, hypertension, and myocardial infarction. Multivariate logistic regression revealed that patients with influenza had a higher risk of all-cause mortality: (odds ratio = 4.87, 95% confidence interval: 3.63-6.54; p < .01). Patients with influenza also had statistically higher odds of developing acute kidney injury, septic shock, and respiratory failure requiring mechanical ventilation. They also had a significantly longer length of stay (34 days versus 26 days) and adjusted cost for hospitalization ($195 345 versus $121 967). CONCLUSION: Our large analysis of real-world data reveals that patients undergoing allo-HSCT that develop HAII are at substantially higher risk of inpatient complications and death.

Trends and in-hospital cardiac complications in patients with atrial fibrillation undergoing allogeneic stem cell transplant: A National Inpatient Sample analysis (2002-2019).

BACKGROUND: Cardiovascular comorbidities increase the risk of transplant-associated complications. However, the impact of atrial fibrillation (AF) as an independent risk factor remains limited. METHODS: The National Inpatient Sample (NIS) database was queried using the International Classification of Diseases codes to identify patients admitted for allogeneic stem cell transplant (ASCT). The patients were then subclassified into with and without AF. Subsequently, a multivariate logistic regression model was constructed to account for patient demographics, comorbidities, and hospital characteristics to evaluate the impact of AF on the primary outcome of interest: all-cause mortality, and secondary outcomes of interest that included common hospitalization complications. RESULTS: The data for 77 157 cases of ASCT were collected between 2002 and 2019. Among these 5086 (6.6%) cases had concurrent AF. Multivariate logistic regression revealed patients undergoing ASCT with AF had almost a three times higher risk of all-cause mortality (odds ratio = 2.99 [95% confidence interval: 2.73-3.28]; p < .01). AF patients also had a higher risk for cardiac arrest, cardiogenic shock, acute kidney injury, and need for hemodialysis (all p < .01). CONCLUSION: AF causes a higher risk of death and cardiovascular complications among patients undergoing ASCT. This signifies the importance of pretransplant consultation and optimization for cardiovascular comorbidities to improve hospitalization outcomes.

Risks and outcomes of hospitalizations in patients with chronic lymphocytic leukemia admitted with immune thrombocytopenia: an analysis of the National Inpatient Sample Database.

Immune thrombocytopenia (ITP) is a known autoimmune complication of chronic lymphocytic leukemia (CLL). Currently, there is limited data regarding the risk CLL confers on hospitalization outcomes in patients admitted with ITP.The National Inpatient Sample (NIS) database was queried using the International Classification of Diseases (ICD) codes to identify hospitalizations for ITP and then subclassified the data into hospitalizations with and without CLL. A multivariate logistic regression was designed to account for patient characteristics and comorbidities. The primary outcome was all-cause mortality. Secondary outcomes included major bleeding, gastrointestinal bleeding, intracranial bleeding, and the need for platelet transfusions, intravenous immunoglobulin, and splenectomy. Among 662,171 cases of ITP between 2005 and 2019, 15,672 had concurrent CLL. CLL patients were significantly older and had more comorbidities compared to patients without CLL. Multivariate analysis revealed CLL patients with ITP had a risk of all-cause mortality (odds ratio: 1.28, 95% CI: 1.19-1.37; p < 0.01). CLL patients also had a higher risk of complications, second-line ITP treatments, blood transfusions, and bleeding, with the exception of intracranial hemorrhage. Our study suggests CLL is an independent risk factor for increased morbidity and mortality among hospitalized patients with ITP. Prospective studies are needed to determine if refractoriness to conventional treatments for ITP can account these results.

The Impact of Atrial Fibrillation on hospitalization Outcomes for Patients With Chronic Lymphocytic Leukemia Using the National Inpatient Sample Database.

BACKGROUND: The incidence of atrial fibrillation (AF) in patients with chronic lymphocytic leukemia (CLL) has been on the rise. However, the excess burden added by AF to the morbidity and mortality of CLL patients especially in the hospitalized setting is undetermined. METHODS: The National Inpatient Sample (NIS) database was accessed to gather data of hospitalized CLL patients with AF from 2009 to 2018. Propensity-score matching (PSM) and logistic regression model were performed to control for baseline patient factors to match 7265 CLL patient admissions with AF and 7265 CLL patient admissions without AF. The primary outcome was all-cause mortality (ACM), while the secondary outcomes included acute coronary syndrome (ACS), acute myocardial infarction (AMI), and the need for percutaneous coronary intervention (PCI), acute heart failure (AHF), acute hypoxic respiratory failure (AHRF), cardiac arrest (CA), cardiogenic shock (CS), stroke, and the total cost of hospitalization. RESULTS: CLL patients with AF had a higher rate of ACM (6.06% vs 4.47%; odds ratio [OR] 1.39, 95% confidence interval [CI] 1.19-1.61; P =< .001). All other secondary outcomes including ACS, AMI, PCI, AHRF, CA, CS, and stroke were observed at a significantly higher rate in the AF group as well. The median total hospital cost was also higher in the AF group ($9097 vs. $7646; P value < .0001) CONCLUSION: CLL patients with AF are at a significantly increased risk of all-cause mortality, cardiac-related mortality, and stroke. For this population, a multidisciplinary approach should be orchestrated for better management and outcomes.

Severe Haemolytic Anaemia Resulting from a Malpositioned Haemodialysis Catheter.

Severe haemolytic anaemia is a rare complication of haemodialysis that is often difficult to recognize, especially when there are other potential differential diagnoses. Here, we present the case of 19-year-old man on haemodialysis who developed severe haemolytic anaemia while recovering from acute renal failure secondary to rhabdomyolysis. Other causes of haemolytic anaemia such as thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome were ruled out. As his blood counts were dropping on days following haemodialysis, haemolysis secondary to the mechanical sheering effect of the catheter was considered and his haemodialysis catheter was exchanged, which led to the resolution of anaemia. LEARNING POINTS: Haemodialysis-related haemolysis can be due to the mechanical sheering effect of the catheter/tubing, and overheating or contamination of the dialysate fluid.Most cases of catheter or faulty tubing-related haemolysis need a high level of suspicion for diagnosis and normally resolve with correction of the underlying mechanical issue.Due to the rarity of the phenomenon, it is very important to rule out other life-threatening causes of haemolytic anaemia, such as disseminated intravascular coagulation and thrombotic thrombocytopenic purpura.

MPL-Positive Essential Thrombocytosis Presenting as Budd-Chiari Syndrome in a Middle-Aged Woman with an Initially Normal Platelet Count.

Budd-Chiari syndrome (BCS) results from an occlusion of the hepatic venous flow which in turn leads to portal hypertension causing ascites and other signs of liver dysfunction. Here, we present the case of a 43-year-old woman with recurrent ascites who was found to have BCS secondary to an inferior vena cava thrombosis extending into the hepatic veins. Although she had a normal platelet count on admission, additional laboratory investigations revealed an MPL mutation. She was discharged on anticoagulation with apixaban and later found to have thrombocytosis on repeat blood work, confirming the diagnosis of essential thrombocytosis, following which she was started on myelosuppressive therapy with hydroxyurea. LEARNING POINTS: Complete work-up to evaluate for myeloproliferative disorders should be done for patients with unexplained thrombocytosis as they are at high risk of thrombotic complications.Ninety percent of patients with essential thrombocytosis have either JAK2, calreticulin or MPL mutation.Patients with essential thrombocytosis who have a thrombotic episode normally require lifelong anticoagulation.

The influence of operation theatre environment on patients' perceptions during awake procedures: a cross-sectional study.

OBJECTIVE: To determine the perceptions of patients regarding operation theatre conversation and environment during an awake procedure. METHODS: The descriptive, cross-sectional study was conducted from February to August 2017 in postoperative wards of Military Hospital, Rawalpindi, Pakistan, and comprised women undergoing gynaecological or obstetric procedures under regional anaesthesia. Closedended questionnaires were distributed via nonprobability convenient sampling. Operation theatre data was collected from the anaesthesia notes, and data was analysed using SPSS 22. RESULTS: There were 93 female subjects with a mean age of 28.23}5.42 years (range: 19-48 years). Overall, 90(96.8%) subjects regarded the conduct of operation theatre staff as cooperative and friendly with 64(68.8%) viewing the conversation among the staff as helpful in relieving anxiety. The thought of anaesthesia waning caused anxiety in 40(43%) subjects, but there was no difference in perceived anxiety between those counselled 61(65%) and not counselled by the anaesthetist. With regards to the environment, 41(44%) subjects said more measures were required to prevent patients from seeing the operating field. Besides, 30(32.2%) and 20(21%)subjects had reservations regarding the presence of male staff and medical students respectively. The opinion regarding medical professionals did not change for 60(64%) subjects after the procedure, and 37(39.8%) recommended that communication skills of medical professional needed improvement. CONCLUSIONS: The environment in the theatre can have an influence on the patient's anxiety levels. Counselling by surgeons, casual conversations in the theatre can help alleviate apprehensions of the patients.