Children with coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), usually present with symptoms of mild upper respiratory tract infection without developing any significant complications. However, this observation has been rendered incautious by hundreds of clinical cases from around the world that have depicted a less benign multisystem inflammatory illness mimicking Kawasaki disease in COVID-positive pediatric patients. Our study aimed at retrospectively reviewing the different features of Kawasaki disease-like illness in children suffering from COVID-19, including the complications, laboratory investigations, treatment strategies used during their hospital stay, and outcomes. We searched the electronic database of the two pediatric units of Mayo Hospital, Lahore, Pakistan, for children who had been admitted to the ward between April 2020 and July 2020 and were diagnosed with COVID-19. A total of 10 such pediatric cases were found, whose clinical details were then reviewed and the obtained data were presented in the form of tables and percentages. The median age was between 4 months to 11 years (mean: 6 years). Of the 10 patients, 8 (80%) were boys. Criteria for Kawasaki disease were met in all of them (100%), with a complete presentation in five (50%). Fever (100%), conjunctival and oral cavity changes (90%), and rash (80%) were the most common features. Seven (70%) patients required admission to a critical care unit, but no mortality occurred. This article can assist in understanding and dealing with Kawasaki disease-like manifestation of pediatric COVID-19 infection, especially in critical care settings, and its possible complications. It will help in a timely and appropriate decision-making regarding treatment and management of such cases.

Open Access Original Article

Introduction: β-thalassemia major (TM) is one of the most prevalent inherited hemoglobinopathies in Pakistan. It has one of the highest prevalence of transfusion-dependent TM patients globally, with an estimated greater than 100,000 active cases. Each year, an estimated 5000-9000 new cases of TM are being diagnosed in the country. Blood transfusions (BT) are essential in the management of severe TM; it is critical to have a safe BT to reduce the risk of transfusion transmissible infections (TTIs). Frequent blood transfusions in these patients increase their risk of acquiring TTIs compared to the general population. In this systematic review, we aimed to identify the prevalence of TTIs in transfusion-dependent β -thalassemia major patients in Pakistan. Methods & Material: We performed a systematic literature search to identify studies related to the TTIs and transfusion-related infections in Pakistan from January 1, 2010, to January 31, 2020. The search was conducted using PubMed and PakMediNet (Largest medical database of Pakistan), with initial search retrieved 981 studies. Among these, 166 studies met the inclusion criteria. After further screening by reviewing the articles for relevance and availability of full-length articles, only 14 studies met the final criteria for qualitative synthesis. Results Analysis of 14 studies (n=3786) showed that the seroprevalence of Hepatitis B virus (HBV) of 3.13% (0.66 % to 7.4%) and Hepatitis C virus (HCV) of 26 % (5.56% to 68.2%). There were only two studies reported HIV seroprevalence of 0 % & 0.5% (n=6). The rate of seropositivity for HBV and HCV was directly related to the number of transfusions, higher ferritin levels, and older age groups. There was an increase in the HCV rate with the increasing age of patients. Thalassemia patients who were older than ten years of age had a greater HCV compared to those who were less than ten years of age, i.e., 22% vs. 8.4%, p:0.005, respectively. The mean age was higher in HCV reactive children than non-reactive children. A comparison of HCV in healthy donors vs. thalassemia patients showed a rate of 1.9% vs. 13.1% for T.M. patients. There was HCV infection rate of 74% in the group with greater than 100 BTs compared to 33 % in a group with fewer than 35 BTs. The rate of HCV increased to 75% for the patients who had more than 100 BTs. The majority of the patients were males (51% to 88%). The seroprevalence of TTIs was higher in males than in females (73.4% vs. 26.6%). On average, a single TM patient is exposed to at least 17 different donors annually, requiring 1-2 transfusions every month. The free BT is accessible only in 1 out of 4 thalassemia centers. The majority of patients either need to bring their donors or are dependent on an external source of financial aid as they could not afford the cost of BT treatment. More than half of thalassemia patients (57.2%) need to contact multiple BT centers to search for required blood products. About 42.1% of parents of TM patients did not know about TTIs, whereas 31.6% of them did not know about the bloodborne transmission of HBV and HCV. The majority of parents of TM children had a low income, with 75% of them having income less than 10,000 Pakistani rupees (PKR) per month. The prevalence of TTIs in TM patients was significantly higher (96% vs. 4%) compared to the patients requiring multiple transfusions due to other causes such as leukemia, aplastic anemia, and thrombocytopenia. Conclusion: Our data highlights that the prevalence of transfusion-transmitted infections, especially HCV, is alarmingly higher (26%) in the TM population than in the general population. This is because of a lack of resources, inadequate safety measures, and a fragmented blood transfusion system. These findings warrant the urgent need for better public health measures, safe blood transfusion practices, voluntary remunerated blood-based transfusions, and universal quality-assured donor screening. Without these positive interventions, the current transfusion system can lead to a further worsening of the situation. Large prospective multi-centered clinical trials are required to understand better the high prevalence of TTIs in patients with TM. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

Background: Patients diagnosed with thalassemia major who are transfusion dependant, have iron accumulation leading to iron toxicity and severe impairment in organs like heart, liver and endocrine organs which are highly sensitive to iron toxicity. This makes iron chelation therapy imperative for these patients. Half of the deaths resulting from iron toxicity related complications are attributed to cardiac complications. Iron chelation therapies have not been completely successful to prevent iron toxicity related complications like arrhythmia, cardiomyopathy and heart failure. Higher doses of iron chelation therapies have been associated with various side effects. Studies have shown L-type calcium channel blocker might be able to reduce iron uptake by myocardium. The aim of this meta-analysis is to assess the efficacy and safety of amlodipine to reduce myocardial iron concentration (MIC). Methods: We used PICO framework to do a systematic literature search using four database PubMed, Cochrane, Embase, and Web of Science using keywords, "Thalassemia" AND "Amlodipine" from the inception till July 2020. The initial search showed 90 articles out of which, six randomized clinical trials (RCT) (N= 226) were selected after exclusion of case reports, case series, preclinical trials, review articles, meta-analysis, and trials not providing any information about preventing iron overload in patients with transfusion dependent thalassemia. We extracted the data for myocardial iron concentration (MIC), myocardial T2, ferritin, hepatic iron/liver iron concentration (LIC), liver T2, left ventricular ejection fraction, response rate and adverse effects. DerSimonian-Laird random effects model was used to derive mean differences along with their 95% confidence interval (CI) using comprehensive meta-analysis version 3.0. Results: In six RCT, 96 patients were tested in experimental group and 97 in control group. In five RCT total number of male participants were 45 in experimental group and 54 in control group. 33 patients had splenectomy in experimental group and 41 in control group. The age range was 8 years to 31 years. The myocardial T2 score increased in amlodipine group compared to standard chelation group with significant mean difference estimated to be -0.62 (95% CI: -0.95-0.29, p-value: <0.001) in favor of amlodipine in meta-analysis of the four trials (Fig 1.). Statistically significant reduction in myocardial iron was seen in two trials on adding amlodipine to standard chelation therapy (N=55) (Table 1.) (Khaled et al and Fernandes et al). Significant difference was reported in liver T2 score and LIC at the end of six months between amlodipine and control group by Khaled et al. But, there was no statistically significant mean difference in serum ferritin and in liver MRI T2 between amlodipine group and control group with mean difference of -1143 (95% CI: -2410 to 124, p-value = 0.07) and -0.06 (95% CI: -0.463 to 0.338, p-value = 0.76) in meta-analysis of four and two trials respectively (Fig 2. And Fig 3.). El-Haggar et al compared amlodipine with spirulina and statistically significant improvement in myocardial T2 and NT-proBNP level was seen in both groups. Spirulina group also showed significant reduction in serum ferritin, which showed spirulina could also help reduce iron overload. Only mild adverse effects were reported by trials (Table 2.). No cases of severe hypotension, palpitation or any other serious adverse effects were seen in the amlodipine group. Conclusion: This systematic review and meta-analysis suggests that addition of amlodipine 2.5-5 mg/day to standard chelation therapy with monitoring for potential adverse effects, could benefit patients with thalassemia major by reducing cardiac iron overload and thus improve survival and quality of life. Future studies are required to study the role of amlodipine in reducing iron overload in endocrine organs that also absorb iron through voltage-gated channels, particularly considering the close association of cardiac siderosis with endocrine complications and the correlation of pancreas and MICs. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

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.

Introduction: Selinexor, an exportin 1(XPO1) inhibitor has demonstrated anti-leukemia activity as a single agent, as well as in combination regimens for the treatment of acute myeloid leukemia (AML). This systematic review aims to explore the efficacy and safety of selinexor based regimens for the treatment of AML. Methods: A systematic literature search was conducted using PubMed, Embase, Cochrane library, ClinicalTrials.gov, ASCO, and ASH meeting websites. The initial databases yielded 698 articles (last updated search until July 20, 2020). After excluding review articles, duplicates, and non-relevant articles, we included data from eight clinical trials (Table 1 and Table 2). Results: Among a total of 286 patients, 259 were evaluated. Selinexor was given as monotherapy to 81 patients and as combination regimens to 178 patients. The total newly diagnosed (ND) AML patients were 48 and relapsed refractory (RR) AML patients were 238. Garzon et al. did a phase I dose-escalation trial (n=81) with selinexor as a single agent in ND-AML and RR-AML patients with a median of three prior lines of therapy. The overall response rate (ORR) was 14%. The median overall survival (OS) was 2.7 months and median progression-free survival (PFS) was 1.7 months. 15% of the patients discontinued the treatment temporarily due to adverse events (AEs). Bhatnagar et al. (n=25) studied selinexor with decitabine, in phase I clinical trial, in ND and RR-AML patients. The ORR was 40% with higher ORR in ND-AML (80%) compared to RR-AML (30%). At a median follow-up of 21.8 months, the median PFS was 5.9 months (95% CI: 2.4-8.7) and median OS was also 5.9 months (95% CI: 3.9-10.4). The PFS was longer for patients who responded to therapy (11.8 months) as compared to those who did not respond to therapy (4.4 months). In phase I/II trial by Daver et al. (n=14) with selinexor and sorafenib in RR-AML patients, the composite complete remission including CR, CR with incomplete blood count recovery (Cri), and CR with incomplete platelet recovery (CRp) was 35.7%. The event-free survival was 1.8 months (0.4-5.0) in FLT3-ITD Inhibitor failure cohort vs 2.1 months (0.7-2.1) in FLT3-ITD inhibitor naive cohort. A single-arm phase I study with selinexor, cytarabine, and daunorubicin was performed testing ND-AML patients by Sweet et al., (n=19). It showed an ORR of 53% and a median OS of 10.3 months (95% CI: 3.74-NR). The early death rate (death ≤ 60 days) was 4.8%. The phase I dose-escalation trial by Weng et al. (n=28) in ND and RR-AML patients with selinexor+cytarabine+mitoxantrone had a better response rate. The ORR was 64% with a higher ORR in ND-AML (87%) compared to RR-AML (38%). The phase I trial by Alexander et al. (n=18) with selinexor+ cytarabine+ fludarabine on RR-AML patients achieved an ORR of 60 % and CR of 33.3%. Fielder et al. (n=38) did a phase II clinical trial on RR-AML patients with selinexor+ cytarabine + idarubicin with 40 mg/m2 selinexor in one cohort (C1) and flat 60 mg dose of selinexor in the second cohort (C2). In C1 37% of patients and C2 40% of patients had previous stem cell transplantation (SCT). The ORR was almost the same in both cohorts, with 55 % in C1 vs 54.5% in C2. The phase I/II trial on RR-AML patients by Abboud et al. (n=40) with selinexor+ cladribine+cytarabine+filgrastim had a total of CR and CRi in 45% of patients with a median overall survival of 7.8 months (95%CI: 5.7-14.1) and median event-free survival of 6.1 months (95% CI: 4.5 - 7.8 months). The main hematological adverse events were pancytopenia and non-hematological adverse events were hypophosphatemia, hyponatremia, gastrointestinal disturbances, and fatigue (Table 2). Conclusion: Selinexor in combination regimens showed superior response rates compared to selinexor alone for the treatment of AML patients. The response rates were better in selinexor based three and four-drug regimens. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

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Introduction: Stigma is a label that differentiates a person from others and associates them with unenviable attributes. There are various forms of stigma: enacted stigma, perceived stigma, and self-stigma manifesting as stereotyping and harboring negative thoughts about the stigmatized group. Stigmatization of the drug abuser leads to effects such as low self-esteem, depression, and personality changes in the stigmatized. Objectives: The purpose of the study is to know the impact of stigma on patients receiving substance abuse treatment in the Psychiatry Department, Mayo Hospital Lahore, Pakistan. Design: Cross-sectional study. Place: Psychiatry Department, Mayo Hospital, Lahore, Pakistan Study Period: Six months (February 22, 2020, to July 18, 2020). Subjects and Methods: A population-based cross-sectional study was conducted in a tertiary care hospital. A total of 100 patients were recruited in the study. The selection was made on laid down criterion after taking due consent. Interviews were conducted through a pretested questionnaire. Data were collected, compiled, and analyzed through SPSS version 20 (IBM Corp., Armonk, USA), and relevant frequency tables were drawn. Results: On analyzing the data, various forms of stigma were observed: enacted stigma (81% as considered less capable), perceived stigma (99% as having difficulties in the job seeking and relationships), and self-stigma (94% in having devaluation thoughts). Self-esteem was maintained (73% were content). Social support was present (76% from family). Moderate depression was seen in 17% of participants. Over 83% of our study population is aged 21 to 40 years, 15% between ages 41 and 60 years, and only 2% ranging between ages 1 and 20. A total of 80% of the population belonged to a low socioeconomic status, and 55% of participants abused opium, heroin, or brown sugar, followed by white crystal use in 37% of the study population. The majority reported the drug abuse duration of 1-5 years (70%). Conclusion: Stigma in its various forms affects the drug abuser undergoing treatment. It results in low self-esteem and mild depression. Individuals from the broader socioeconomic range can be added in future studies, and a larger population can be studied by collecting data from other tertiary care hospitals and mental healthcare facilities. They can be assessed for factors contributing to their addiction and the challenges they had to go through to get the help they needed.