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Thalassemia major (TM) is the most common deadly genetic disorder, a major cause of chronic non-infectious morbidity and financial burden in many low and middle-income regions. In these settings few children reach adulthood because proper long-term supportive care is seldom available. Bone marrow transplantation (BMT) is the only available curative modality and it can be very successful and cost-effective for young children with low-risk features and a compatible related donor. However, in countries where TM is most prevalent, there is a dire shortage of BMT centers. The Cure2Children Foundation has supported a feasibility study evaluating safety, efficacy and costs of developing a new BMT center in an underserved lower-middle-income country with relatively untrained professionals within a structured collaboration and knowledge-transfer program. A total of 24 consecutive patients who underwent BMT in Pakistan between September 2008 and August 2010 are included in this prospective analysis, 17 from an established bone marrow transplant center, the National Institute for Blood Diseases in Karachi, Pakistan and the initial 7 BMTs from a start up unit in a government civil hospital, the Pakistan Institute of Medical Sciences Children’s Hospital in Islamabad. Patients were matched for age, nutritional status, growth, disease, disease status and post-BMT follow-up time. All patients had a matched-related sibling donor, were younger than 10 years of age at the time of transplantation, received the same conditioning regimen. All needy families could rely on a support program throughout the 8-month post-transplant period. The Cure2Children Foundation provided professional and financial support as well as a structured web-based data management and cooperation platform. At a median follow up of 19.6 months (range 8.7 to 31.5) actuarial thalassemia-free survival is 85.6% and 85.7% and overall survival 94.1% and 85.7% in the established and start-up center respectively with no statistically significant differences. Other outcome indices like infectious complications, engraftment parameters, transplant-related complications, and post-BMT performance scores also did not differ. The median cost of matched-related transplants in the start-up center, including pre-BMT evaluation, was 11,513 USD (range 7,518 to 21,176). Within structured cooperation strategies bone marrow transplantation for thalassemia major can be performed safely, effectively, and affordably even in start-up centers in lower-middleincome countries, like Pakistan, were most thalassemia patients live. This observation may have important implications to increase access to cure for thalassemia worldwide. 重型地中海贫血（TM）是最常见的也是最致命的基因错乱，在许多中低收入地区，基因错乱是造成非传染性慢性疾病和经济负担的重大原因。 在这种情况下，许多儿童因接受不到长期支持治疗而活不到成年。 骨髓移植（BMT）是目前唯一能治愈该疾病的方法。若病患儿童有低风险的特点并且具有匹配的捐献物， BMT 将是治疗幼童成功且低成本的疗法。 然而，在重型地中海贫血多发国家，严重缺乏骨髓移植中心。 第二治愈儿童基金会与来自结构化合作和知识转换计划的未受训专业人员共同资助了一个可行性研究，评估在服务不到位的中低收入国家发展一个BMT中心的安全性、疗效和成本。 本预期分析收录了2008年9月到2010年10月间先后在巴基斯坦接受BMT的24名病人。其中，17名病人在成立的骨髓移植中心位于巴基斯坦卡拉奇市国家血液病研究所,完成手术；最先的7名在市立政府医院位于巴基斯坦医学研究院伊斯兰堡儿童医院,完成手术。 分析中，对比了病人的年龄、营养状态、发育、疾病、疾病状态和MBT后的随访时间。 所有病人都有一名相匹配的同胞捐献者。移植手术时，他们的年龄都在10岁以下，并都接受了相同的预处理方案。 所有困难家庭在骨髓移植手术后的8个月期间都可以得到资助计划的帮助。 第二治愈儿童基金会提供了专业上和经济上的支持以及结构化网络数据管理和合作平台。 在进行平均19.6个月的随访中（(8.7月-31.5月），在已成立的和新运作的卫生中心，地中海贫血症救活率保险估计为85.6% 和85.7%，总生存率为94.1%和85.7%。在统计上无明显区别。 其他结果指标，如传染性并发症、植入参数、移植相关并发症和BMT后表现分数等，都没有区别。 新运作卫生中心匹配相关移植手术的平均成本为11,513 USD （7,518至 21,176），包括BMT前评估费。 在结构化合作策略下，重型地中海贫血（TM）患者骨髓移植手术可以在诸如巴基斯坦等中低收入国家的新运作卫生中心进行，安全、有效，而且价格合理。通过这种手术，大多数病人都可以存活下来。 该观察对提高全球地中海贫血患者接受治疗具有重要意义。

Introduction: There are huge numbers of drilling platforms in the world and once the worker on those platforms meet with an accident, the situation could be very serious. The consequence of this could be environmental, economic and in some cases fatal. Middle East, being one of the oil rich regions hence some of the largest operator works here. Companies here own various types of jack up rigs ranging from old generation rigs to the latest cyber-rig. This paper addresses what oil rig workers have to say about their interaction with machines, and how Human Machine Interaction (HMI) in Offshore Drilling can be improved with design. Method: A case study approach was undertaken The analysis in this paper draws on the interviews conducted with two different employees involved in operating the drilling operations conducted in the driller’s cabin of newly designed offshore rigs. A semi-structured approach was adopted, using themes identified through analysis of the preceding. The interviews were transcribed by the research team. Each interview was analyzed thematically with existing system and reported discrepancy Results: The study on Human Machine Interaction (HMI) and Human Factor regarding this has been conducted in the latest generation cyber rigs. There are many aspects of HMI and ergonomics but in this study a special concentration has been given to deal with the ergonomic standpoint and evaluates the drillers console controls. Conclusions: When comparison is done with the existing machinery, few modifications can be thought of for better human machine interaction. A better human machine interaction system will ensure a more productive environment for the oil-rig workers.

Background and objective Allogeneic hematopoietic stem cell transplantation (alloHSCT) provides curative treatment for several hematological illnesses. In this study, we evaluated the impact of ABO compatibility and incompatibility on outcomes and complications related to hematopoietic stem cell transplantation (HSCT) performed for various hematological disorders at our center. Methodology This was a retrospective, single-center, cohort study in which patients were categorized according to the ABO match and mismatch status. The mismatch group was further subcategorized into major, minor, and bidirectional groups. Results A total of 117 patients underwent alloHSCT, out of which 82 (70.1%) were male and 35 (30%) were female. The median age of the patients was 9.5 years (range: 46 years). The most common indications for stem cell transplant were beta-thalassemia major (BTM; n=58, 49%) and aplastic anemia (AA; n=42, 35.8%). However, the outcomes in match and mismatch groups showed significant results for positive direct Coombs test (DCT), indicating the occurrence of hemolysis. Despite the increased need for blood transfusions, ABO blood group incompatibility (ABOi) had no negative impact on the clinical results. Conclusion Based on our findings, ABO incompatibility does not affect the outcomes in patients undergoing alloHSCT. Patient monitoring can aid in early detection and treatment, thereby minimizing the frequency of fatal events., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Borhany et al.)

Aim and objective This study aimed to examine the relationship between serum ferritin levels and the degree of hepatic fibrosis as detected on Fibroscan in thalassemia patients. Materials and methods This was a single-center and cross-sectional study conducted from April 2021 to December 2022. The sample population comprised 55 beta-thalassemia patients receiving treatment at the National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan. The data was compiled through a series of patient interviews, an examination of medical records and was analyzed to obtain the results. Descriptive statistics were used for several variables, including diagnosis, Fibroscan score, blood group, comorbidity, visceromegaly, consanguinity, serum glutamate pyruvate transaminase (SGPT), viral markers, and C reactive protein (CRP). The correlation analysis was done using Spearman's correlation test. Results There were 55 participants in the study, 40 of whom were male and 15 of whom were female. The mean age of the patients was eight years, while the average age at diagnosis was nine months with a transfusion frequency of every 20 days. Spearman's rho (r = 0.287), and the significant value of (p = 0.033) confirmed a statistically significant positive correlation between serum ferritin levels and hepatic fibrosis. On Fibroscan, 74.5% of patients had F0-F1 stage fibrosis followed by 14.5% of the patients having F2 stage fibrosis. HCV seropositivity was the most prevalent comorbidity among the patients. 80% of patients had serum ferritin levels greater than 1000 ug/mL. Hepatosplenomegaly was present in 43.6% of the patients. 78.2% of patients were born out of consanguineous marriages. Conclusion In conclusion, this study found a statistically significant positive correlation between serum ferritin levels and hepatic fibrosis in beta-thalassemia patients. The study emphasizes the significance of monitoring serum ferritin levels in thalassemia patients to prevent hepatic fibrosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ali et al.)

Objective: This study aimed to compare the reticulated platelet count between patients having thrombocytopenia secondary to autoimmune destruction (immune thrombocytopenia {ITP}), bone marrow failure, and healthy controls who presented to a tertiary care hospital in Karachi, Pakistan., Methodology: A cross-sectional study was conducted from February 2021 to October 2022 in the Department of Hematology, National Institute of Blood Disease (NIBD) Hospital in Karachi, Pakistan, that involved examining three groups: 30 patients with immune thrombocytopenia, 30 patients with thrombocytopenia secondary to reduced production from bone marrow, and 30 healthy controls. The study utilized the Sysmex XN-1000 (Hyogo, Japan: Sysmex Corporation) automated hematology analyzer to perform a complete blood count (CBC) test. Additionally, peripheral blood was stained with Leishman stain and examined under a microscope to eliminate pseudo thrombocytopenia and identify any abnormal cells or dysplasia. The immature platelet fraction (IPF) was then performed on Sysmex XN 1000 after ensuring adequate quality control. Finally, the data were analyzed using DATAtab (Graz, Austria: DATAtab) and SPSS version 25 (Armonk, NY: IBM Corp.)., Results: Of the ninety participants, the median age was 33 years with a range of 18-71 years. Patients with ITP had a significantly higher median IPF% (median=26.65, IQR=15-39.4) than thrombocytopenia due to bone marrow failure (median=9.25, IQR=4.55-14.30) and healthy controls (median=7, IQR=4.40-9.90), with a p-value of 0.001. The immune thrombocytopenia group demonstrated an increase in IPF% as platelet counts increased, indicating a significant moderate correlation between IPF% and platelets in these patients (r=0.438, p=0.016) and confirming that IPF% was an independent predictor for the detection of ITP., Conclusion: Reticulated platelet count may be a useful diagnostic tool to differentiate between ITP and thrombocytopenia caused by bone marrow failure. Because of its non-invasive nature, IPF is a valuable tool for expediting the management of thrombocytopenia associated with increased IPF., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Butt et al.)

Background and objective Tracheostomy in coronavirus disease 2019 (COVID-19) patients can be performed in cases of prolonged intubation or in patients with a known difficult airway. Tracheostomy is usually performed by two main approaches: open surgery or percutaneous endoscopic insertion. However, few studies have compared these two techniques in severe COVID-19 patients. The objective of the present study was to compare the efficacy of the two main methods of tracheostomy among patients with severe COVID-19 infection. We also aimed to investigate the impact of various lab data and medications on patient outcomes. Materials and methods We included all symptomatic severe COVID-19 patients in need of prolonged mechanical ventilation. We examined the patients' past medical history, arterial blood gas (ABG) analysis, laboratory workups, and medication history. We calculated the PaO 2 /FiO 2  ratio as an index to evaluate the severity of acute respiratory distress syndrome (ARDS). Results During the study period, 72 patients with severe COVID-19 underwent tracheostomy tube insertion. The average age of participants was 58.93 ±15.27 years; 44 (61.1%) were male and 28 (38.9%) were female. Of note, 54 (75.0%) patients passed away and only 18 (25.0%) survived. Among the survivors, 13 (29.5%) were men and five (17.9%) were women. The study showed a significantly higher mortality rate (23, 92.0%) among patients who underwent open surgery compared to those who received percutaneous surgery (31, 65.9%) (p=0.01). Conclusion Based on our findings, percutaneous endoscopic tracheostomy seems to be the superior approach compared to open tracheostomy. Other predictive factors associated with patient outcomes included levels of HCO 3 , FiO 2 , PaCO 2 , and PaO 2 /FiO 2 ratio., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Akbari et al.)

Objectives: To establish a reliable XN-HPC cutoff, for an effective CD34 + cell count of ≥2 × 10 6 cells/kg of the recipient's body weight, in harvested bone marrow products in allogenic transplantation., Methods: The study was carried out in two phases. In retrospective Phase 1, data from 47 donors were analyzed. Sysmex analyzer XN-20 and BD FACS Calibur were employed to process XN-HPC and CD34 + cell enumeration, respectively. To make the two variables comparable, both XN-HPC and CD34 + cell counts were reported as the number of cells/kg of the recipient's body weight. Spearman's rank correlation coefficient was calculated for CD34 + cells and XN-HPC, followed by the calculation of the receiver operating characteristic (ROC) curve to identify the XN-HPC value which could effectively predict the cutoff of ≥2 × 10 6 CD34 + cells/kg of the recipient's body weight. In Phase 2, the computed XN-HPC cutoff was validated in a prospective set of 53 donors by obtaining the positive and negative predictive values., Results: Statistically significant correlation was obtained between XN-HPC and CD34 + cell count with Spearman's rho of 0.54 ( p -value <0.001). The optimal XN-HPC cutoff, for the required CD34 + ve cell count of ≥2 × 10 6 cells/kg of the recipient's body weight, was calculated to be ≥2.80×10 6 cells/kg of the recipient's body weight with the specificity and sensitivity of 100% and 31%, respectively. The ROC curve demonstrated the area under the curve to be 0.74. Phase 2 validation revealed 100% PPV., Conclusions: For harvested bone marrow products with XN-HPC of ≥2.80×10 6 cell/kg of the recipient's body weight, CD34 + cell enumeration by flow cytometry can safely be disposed of.

Background: This study was carried out to determine the frequency of CD34 positivity in acute lymphoblastic leukaemia (B-ALL) in our population and to report its association with the clinicopathological profile at the time of diagnosis., Methods: The cross-sectional study was conducted at National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan, from March 2020 till December 2020.Newly diagnosed patients were selected, from both genders and all age groups. Relevant history and findings of physical examination were recorded. Immunohistochemistry was done on trephine biopsy and molecular studies were carried on bone marrow aspirates or peripheral blood samples., Results: Out of 105 patients enrolled, 67 (63.8%) were males, with a male to female ratio (M: F) 1.8:1. Of the total patients, 62 (59.04%) were above 15 years of age. CD34 was expressed in 73 (69.5%) cases. Lymphadenopathy, splenomegaly, and hepatomegaly were separately noted in context to CD 34 expression in 22 (66.6%), 24 (64.8%), and 14 (58.3%) patients, respectively. CNS disease was seen in a total of 3(2.75%) subjects, in which 2 (66.6%) of the patients had CD34 expression. Total 81 patients in our study fall into the high-risk group out of which CD 34 expression was seen in 58(71.6%) subjects. Cytogenetic analysis, BCR-ABL p190, and MLL gene rearrangement were investigated in all participants. Cytogenetic analysis revealed an abnormality in 20 (19%) cases out of which 13 (17.8%) cases were from CD34 positive group., Conclusion: Our study reported CD34 expression in more than two-thirds of cases. High-risk disease was significantly associated with CD34 expression.

Background: Myelodysplastic syndromes (MDS) are heterogeneous group of haematopoietic stem cell disorders and have variable reduction in the production of red cells, platelets and mature granulocytes., Aim: We conducted a case-control study evaluating the environmental and occupational determinants as risk factors of MDS., Methods: A case-control study was conducted including 150 de novo MDS cases and 450 age and gender-matched controls. Disease characteristics, sociodemographics and exposure to environmental and occupational determinants were collected through a questionnaire. Chi-square test was applied to observe association, and binary logistic regression was applied to predict the odds of having MDS., Results: A total of 600 participants were analysed. Those who were exposed to arsenic (OR 31.81, CI: 19.0-53.0, P-value: .000), benzene (OR 1.564, CI: 1.07-2.27, P-value: .01) using natural source of water (OR 3.563, CI: 2.29-5.53, P-value: .000) and smokers (OR 3.1, P-value: .000) were more likely to have MDS. Unmarried were less likely to acquire MDS than married (OR 0.239, CI: 0.15-0.36, P-value: .000), Sindhi speaking were 1.419 times more likely to have MDS than participants speaking other languages. Uneducated participants were more likely to have MDS than educated and powder milk users were more likely to have MDS than dairy milk users., Conclusion: Our results revealed that arsenic, use of natural source of water and benzene exposure might lead to higher risk of acquiring MDS. This study would be helpful to understand the aetiology of disease in Pakistani population., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background: To systematically review and summarize the available literature regarding the women's sexual function during COVID-19 pandemic and compare it to pre-pandemic period., Methods: We searched PubMed and Embase from the inception of the databases until 15th April 2021. Data regarding the sexual function, measured by female sexual function index (FSFI), of adult sexually active women were extracted from the eligible studies and compared between the before and during the COVID-19 pandemic. The secondary outcome was the frequency of intercourse during pandemic time. The random-effect model was used to pool the mean differences and corresponding 95% confidence intervals (CIs). Heterogeneity was assessed using the I 2 value., Results: Our search resulted in a sample of six eligible studies, which involved 1114 female participants. The total FSFI score among study participants during pandemic was 22.93 (95% CI: 19.26-26.59), which indicated a significant decrease in sexual function of women during pandemic as compared to pre-pandemic time (mean difference = -3.80, 95% CI: -6.48 to -1.12, p = 0.005, I 2  = 96%). We also conducted a meta-analysis of individual FSFI domains. During pandemic, women had problems with arousal (p < 0.0001), orgasm (p = 0.0008), satisfaction (p = 0.0009), and pain (p = 0.009). No significant difference in frequency of intercourse was observed between pre- and during pandemic (p = 0.80). Furthermore, no significant publication bias was present among included studies., Conclusion: Overall, there was a significant decrease in sexual function of sexually active adult women during COVID-19 pandemic. The most affected areas of sexual function were arousal, orgasm, pain, and satisfaction. Physicians must be aware of COVID-19 impact on sexual life of women and provide proper counseling., (© 2022 Japan Society of Obstetrics and Gynecology.)

The red blood cell membrane loses its integrity during hemoglobinopathies like β-thalassemia and sickle cell disease. Various mutations have been associated with β-thalassemia, the most prevalent of which is the IVS-1-5 (G > C) mutation. It is associated with poor prognosis of the disease with a dependency on transfusion. Here, we have investigated the effect of IVS mutation and the administration of hydroxyurea on the red blood cell membrane lipidome isolated from patients using a liquid chromatography coupled to tandem mass spectrometry based approach to identify changes in the red blood cell membrane lipidome of patients with/without the mutation and being/not being administered hydroxyurea. A total of 50 patients, with/without hydroxyurea treatment, were recruited and 62 lipid species were identified in all groups after statistical analyses using fold change analysis, ANOVA and lipids with higher VIP values extracted from the OPLS-DA loading plot. The presence of the IVS mutation showed altered expression levels of various lipid species as compared to non-IVS individuals, such as phosphatidylcholines, steroids, phenol lipids and fatty acids. Significant changes were though found with the administration of hydroxyurea where both the IVS and non-IVS groups showed a marked increase in complex lipids of the membrane, while a decrease was observed in those without hydroxyurea administration showing degradation of these membrane lipids. This study is the first to report changes incurred by IVS mutation and hydroxyurea administration in red blood cell membranes extracted from β-thalassemia patients. Hydroxyurea administration has been perceived to improve the lipid profile of the red blood cell membrane in both IVS and non-IVS patients.

Background: Anal fissure is a linear tear in the distal anoderm most frequently occurring in the posterior midline. Lateral internal sphincterotomy is considered the gold standard for the treatment of this condition. To this date, several pharmacological and neuromodulatory therapies have been tried out as alternative non-invasive treatments for anal fissures, however, the efficacy of some of these methods remains to be understood., Objective: the primary aim of this study was to review available literature on neuromodulatory treatments for recurrent anal fissure as a potentially effective cure for this condition., Data Sources: A search was conducted among five main online databases Embase, PubMed, Web of Science, Scopus, and Scholar., Study Selection: All published human studies in English literature addressing neuromodulation for the treatment of recurrent anal fissure were selected., Intervention: neuromodulation for the treatment of anal fissure. We chose to include all articles in which the authors stated that the procedure they performed was via neuromodulation technique, or that the described technique used in their study resembled the technique., Result: Among a total of 3487 evaluated studies, seven represented the effects of neuro modulation on treatment of recurrent anal fissure, among which two were randomized controlled trials and the rest were prospective studies. A total of 186 patient were evaluated in these studies. The mean age of the participants was 46.97 ± 8.2. The average VAS score before intervention was 7.77 ± 2.13, which decreased to 0.31 ± 1.13 after intervention., Limitations: limitations of this study include the lack of related articles, and data regarding this subject., Conclusion: Posterior tibial nerve stimulation (PTNS) provides rapid pain relief and fissure healing especially in short-to mid-terms with little to no complications, however, using this treatment, symptoms of anal fissure do not improve as well as LIS, especially in the long-term., (Copyright © 2022 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

RBCs membrane loses its integrity during hemoglobinopathies such as β-thalassemia and sickle cell disease. The severity of β-thalassemia has been historically linked to the presence of XMN polymorphism which is believed to ameliorate the severity. Here, we investigate the effect of XMN polymorphism on RBC membrane lipidome isolated from patients, using LC-MS/MS based approach. A total of 50 patients were recruited and 28 lipid species were identified in all groups after statistical analyses using volcano plot and ANOVA-SCA, and lipids with higher VIP values extracted from OPLS-DA loading plot. Alteration in lipid levels specifically the membrane lipids such as PC and fatty acids were observed. Samples with XMN polymorphism exhibited up-regulation of lipids involved in membrane stability such as cholenoic acid while PC (O-41:1) was down-regulated when compared to non-XMN samples. Additionally, HU administration to samples also had profound effect on the lipids of patients in both groups. A trend of improvement in the membrane lipids was observed in patients with XMN polymorphism. HU administration has proven to further improve the membrane integrity by upregulating certain membrane lipids in such patients. The study presents a comprehensive analysis of RBC membrane lipidome with respect to the genetic variation and HU administration., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: The study aimed to evaluate the causes of thrombocytopenia in pregnancy and its management along with the outcome in the COVID-19 era., Methods: Recruitment for this prospective, cross-sectional observational study of thrombocytopenia in pregnancy (platelet counts <100x10 9 /L) was done from January 2017 to August 2020 at the National Institute of Blood Diseases (NIBD) after taking the patients' informed consent. Complete clinical and lab profile of patients was also collected., Results: A total of 150 pregnant women with thrombocytopenia were enrolled, with the mean age being 27.3±4.64 years. Mean platelet counts at baseline were 48.0±24. Main clinical manifestations at baseline included: anemia 65.9%, bruises 23.25%, and edema 9.3%. Causes of thrombocytopenia were gestational thrombocytopenia (GT) 72 (48%), acute fatty liver five (3.3%), pre-eclampsia in 11 (7.3%), and eclampsia seven (4.6%). Causes not specific to pregnancy included 30 (20%) cases of ITP, hepatitis C, and nutritional deficiency was reported in nine (6%) patients each. 72/150 received supportive care treatment to manage thrombocytopenia and were closely monitored and given supplements. Twenty (66.6%) ITP patients received treatment with steroids, with complete response in 70% of them seen. Overall, 38 (25.3%) women with bleeding symptoms and platelet count <50x10 9 /L received platelet transfusions., Conclusion: The study shows that pre-eclampsia and eclampsia are serious conditions with a high risk for complications, while GT is a benign and the most common cause of thrombocytopenia in pregnancy which requires no active treatment. The other causes such as ITP and infections require individualized management., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Borhany et al.)

Background An adequate supply of quality blood products is the backbone of any hospital. To maintain it, the utilization and wastage of the products should be closely monitored. Objective To determine the crossmatch to transfusion (C/T) ratio, transfusion probability (%T), and transfusion index (Ti) of packed red blood cells and to review the use of platelets. Materials and methods A total of 6,326 hematological patients receiving packed red blood cells were included in the study. The random donor platelets that were prepared during this period were also included to know the actual utilization of platelets. Results A total of 26,146 crossmatches were requested for these 6,326 patients in three years. Out of these, 26,024 units were issued and transfused to the patients. The CT ratio of our data was calculated to be 1.00, the transfusion probability was found to be 98.1%, and the transfusion index was computed to be 0.99. For random donor platelets, 37,162 were prepared from whole blood during this period, while 30,971 platelets were transfused to the patients. Conclusion The overall results of our analysis showed proper utilization of blood products at our institution. The wastage was considered to be minimal., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Waheed et al.)

Background: Human milk banks play an essential role by providing human milk to infants who would otherwise not be able to receive mother's milk., Study Aim: To determine the opinions and attitudes among possible donor mothers regarding human milk banks in one rural region in Bangladesh., Methods: A prospective, cross-sectional study following a probability type of stratified cluster sampling technique was used. Included in the study ( N = 121) were mothers aged 20-49 years, with at least one child, who was currently lactating or had breastfed her child, and who resided in the rural community of Bangladesh where the study was conducted. Data were collected through a 21-item, close-ended questionnaire and a face-to-face interview conducted by the researcher at each participant's home., Results: Among the participants, 98.3% ( n = 119) said that they had not heard about human milk banks before speaking with the researchers. Most participants (71.9%, n = 87) said would obtain human milk from milk banks if necessary, but 28% ( n = 34) of mothers indicated that they would not receive milk from a milk bank, even if it was necessary for their children. Only 8.3% ( n = 10) said human milk banks were not appropriate according to Islam and 99.2% ( n = 120) did not know about the acceptance of human milk banking practices in Bangladesh., Conclusions: For those with religious concerns, a framework for both the donors and recipients can be established. It can be recommended that health education through healthcare personnel (midwives, nurses, gynecologists, pediatricians, and other health professionals) and religious leaders may strengthen the belief and increase awareness among family members about milk banking practices.

Background: Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem cells exhibiting ineffective hematopoiesis and tendency for transformation into acute myeloid leukemia (AML). The available karyotyping and fluorescent in situ hybridization provide limited information on molecular abnormalities for diagnosis/prognosis of MDS. Next generation DNA sequencing (NGS), providing deep insights into molecular mechanisms being involved in pathophysiology, was employed to study MDS in Pakistani cohort., Patients and Methods: It was a descriptive cross-sectional study carried out at National institute of blood diseases and bone marrow transplant from 2016 to 2019. Total of 22 cases of MDS were included. Complete blood counts, bone marrow assessment and cytogenetic analysis was done. Patients were classified according to revised WHO classification 2016 and IPSS score was applied for risk stratification. Baseline blood samples were subjected to analysis by NGS using a panel of 54 genes associated with myeloid malignancies., Results: The median age of patients was 48.5 ± 9.19 years. The most common presenting complaint was weakness 10(45.45%). Cytogenetics analysis revealed abnormal karyotype in 10 (45.45%) patients. On NGS, 54 non-silent rare frequency somatic mutational events in 29 genes were observed (average of 3.82 (SD ± 2.08) mutations per patient), including mutations previously not observed in MDS or AML. Notably, two genes of cohesin complex, RAD21 and STAG2, and two tumor suppressor genes, CDKN2A and TP53, contained highest number of recurrent non-silent somatic mutations in the MDS. Strikingly, a missense somatic mutation p.M272Rof Rad21 was observed in 13 cases. Overall, non-silent somatic mutations in these four genes were observed in 21 of the 22 cases. The filtration with PharmGKB database highlighted a non-synonymous genetic variant rs1042522 [G > C] located in the TP53. Genotype GG and GC of this variant are associated with decreased response to cisplatin and paclitaxel chemotherapy. These two genotypes were found in 13 cases., Conclusion: Sequencing studies suggest that numerous genetic variants are involved in the initiation of MDS and in the development of AML. In countries like Pakistan where financial reservation of patients makes the use of such analysis even more difficult when the availability of advanced techniques is already a prevailing issue, our study could be an initiating effort in adding important information to the local data. Further studies and large sample size are needed in future to enlighten molecular profiling and ultimately would be helpful to compare and contrast the molecular characteristics of Asian versus global population., (© 2021. The Author(s).)

Background and objective The calcineurin inhibitor cyclosporine A is routinely used for prophylaxis against graft-versus-host-disease (GvHD) in human leukocyte antigen (HLA)-matched allogeneic stem-cell transplant patients and is a major etiological factor for neuropathological symptoms that are reversible in most cases. In this study, we aimed to determine the frequency and risk factors of cyclosporine-induced neurotoxicity (CIN) in HLA-matched allogeneic stem cell transplant patients. Methods The study spanned the period from January 2016 to December 2019. Consecutive HLA-matched allogeneic stem-cell transplant patients of all ages were included in the study. Descriptive and risk factor analyses for the development of CIN with respect to age, sex, primary diagnosis, conditioning regimen, electrolyte abnormalities, and cyclosporine trough levels during the neurological episode were performed. Results A total of 106 HLA-matched patients with a median age of 6.3 years [interquartile range (IQR): 0.5-46 years], of which 37 (35%) were females, were included in the study. The mean cyclosporine trough level was 500 ±286 mg/dl. Neurological symptoms were found in 27 (26%) patients. A total of 14 (13%) patients were diagnosed with CIN. The frequency of other neurological symptoms included headache in 46 (43%), disorientation in 17 (16%), seizures in 12 (11%), visual disturbance in 11 (10%), and aphasia in seven (7%) patients. Posterior reversible encephalopathy syndrome (PRES) was found in six (6%) patients. All patients with CIN had hypertension and none had a fever. Multivariate logistic analysis showed that the presence of seizures [odds ratio (OR): 10.0, p<0.001] and the absence of fever (OR: 0.02, p<0.001) were associated with the diagnosis of CIN. Conclusion The prevalence of CIN is not uncommon (13%) in patients receiving cyclosporine for GvHD prophylaxis. Neurological complications, especially seizures, are common in CIN, and fever might indicate an alternative diagnosis. Prompt recognition of neurological signs and symptoms and early intervention can halt the progression of the disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Danish et al.)

Background: The recent pandemic by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global emergency. There is large number of asymptomatic cases of SARS-CoV-2 that are not reported. Hence, serological evidence of SARS-CoV2 antibodies is warranted for a better estimation of the actual number of infected patients to limit the disease spread and to get an idea of herd immunity., Methods: This is a cross-sectional study conducted from May 2020 to July 2020 at National Institute of Blood Diseases at Pakistan. The study includes healthcare workers (HCWs), community and industrial workers. The anti-SARS-CoV-2 test was performed by electrochemiluminescence immunoassay analyzer., Results: A total of 1675 samples have been received from three groups of population. The percentage positivity for industrial employees is high (50.3%) for HCW (13.2%) and community population (34%).Total percentage for positive antibodies result is ~36%., Conclusion: Our seroprevalence is 36%, which still far from herd immunity that needs to be at least 60-70% in population. If we consider acquiring 60% seroprevalence in next few months, then herd immunity is not far from reality, provided the antibodies did not decline with time. Although the current study is based on a small sample of participants, the findings suggest a study with larger population to implement stronger and targeted interventions., (© The Author(s) 2020. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The tet oncogene family member 2 ( TET2 ) gene has been reported to be involved in DNA methylation and epigenetic regulation in acute myeloid leukemia (AML). Various studies have proven functional role of TET2 mutations in AML. We herein studied the frequency and genotype-phenotype correlation of TET2 gene in AML patients in Sindh, Pakistan., Patients and Methods: The current study was carried out at Liaquat University of Medical & Health Sciences, Jamshoro, Pakistan, in collaboration with National Institute of Blood Disease & Bone Marrow Transplant, Karachi, Pakistan, during the period from June 2019 to June 2020. A total of 130 patients diagnosed with AML were screened for TET2 mutations. Whole exome sequencing of 14 individuals was carried out to find the genetic variants in TET2 gene. The pathogenicity of the variants was predicted by SIFT, PolyPhen2, Mutation Taster and CADD Phred scores. The allele frequency of the variants was compared with global population using 1000 genomes project and Exome Aggregation Consortium (ExAC). Furthermore, exon 3 and exon 5 of the TET2 gene were sequenced by using Sanger sequencing. The findings were correlated with subtypes of AML and corresponding karyotypes., Results: Through the exome sequencing, 17 genetic variants (13 SNPs and four indels) were identified in 14 individuals. Of these, four variants that is, one frameshift deletion, one frameshift insertion and two nonsense variants were novel and not present in dbSNP151 database. Three novel variants were found in exon 3 including two frameshift variants that is, p.T395fs and G494fs, predicted as deleterious by CADD Phred scores, and one stop-gain variant (p.G898X) predicted as deleterious by Mutation Taster and CADD Phred scores. One novel non sense variant (p.Q1191X) was found in the exon 5 predicted as deleterious by SIFT, Mutation Taster and CADD Phred scores. Sanger sequencing analysis revealed one novel deletion at g105233851: del.TAGATAGA, and one novel SNP g;105233861 T>G identified in the TET2 gene. Majority of the exon 3 mutations were seen in the patients diagnosed with AML with maturation, and had a normal karyotype., Conclusion: TET2 mutations were identified in around 16% of the total patients of our study indicating other mechanisms being involved in pathophysiology of AML in this cohort. The TET2 mutations provide a prognostic value in determining AML classification., Competing Interests: The authors declare that they have no competing interests., (© 2021 Shaikh et al.)

Aims: To assess the seasonal variations in hematological disorders among patients diagnosed on the basis of bone marrow biopsy, who attended National Institute of Blood Diseases (NIBD) clinics during 2006 to 2015., Methods: We retrospectively reviewed the 10-year records of hematological disorders among patients' NIBD clinics from year 2006 to 2015. All cases of aplastic anemia (AA), acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), immune thrombocytopenic purpura (ITP), and acute promyelocytic leukemia (APML) were categorized on the basis of the seasons in which they were diagnosed such as winter (December-February), spring (March-May), southwest monsoon periods (June-September), and retreating monsoon period (October and November). Statistical analysis was performed by using SPSS and STATA. Inferential statistics were explored using the chi-square test for heterogeneity to evaluate seasonal variations. P-value <0.05 was taken as significant., Results: A total of 1982 cases were reviewed. Men were predominantly higher (n = 1190, 60%) as compared to women (n = 792, 40%). Frequency of ALL was found to be higher (513, 25.9%), followed by ITP (504, 25.4%), AML (490, 24.7%), AA (396, 20%), while APML was observed in only 79 (4%) patients. Seasonal variations in the diagnosis of hematological disorders were observed (P-value < .001), except in APML diagnosis (P-value = .445). Significant seasonal variations were also detected in both genders in stratified analysis., Conclusion: The finding of this study has reported an increase in the hematological disorder during 2006 to 2015. Particularly, majority of the cases were reported in southwest monsoon period, whereas least cases were reported in retreating period. Significant seasonal and yearly variations were detected in all diagnosis except the APML., (© 2020 John Wiley & Sons Ltd.)

Objective: To evaluate the presence and characteristics of additional karyotype abnormalities in chronic myeloid leukaemia cases., Methods: The cross-sectional study was conducted at the Department of Cytogenetics and Molecular Pathology, National Institute of Blood Diseases and Bone Marrow Transplant, Karachi, from May 2010 to September 2016 and comprised diagnosed chronic myeloid leukaemia patients regardless of age and gender. Baseline cytogenetic evaluation was done on overnight, 24-hrs un-stimulated and 72-hrs stimulated bone marrow cultures, and karyotypes were defined according to the International System for Human Cytogenetic Nomenclature2013. Data was analysed using SPSS 23., Results: There were 222 cases with a median age of 38 years (range: 12-84 years). The male-to-female ratio was 1.8:1. Chronic myeloid leukaemia was detected in 18(8.1%) patients having additional cytogenetic abnormalities. Among the patients found positive, cytogenetic type was minor in 10(55.55%), major 3(16.66%), complex 3(16.66%), and variant 2(11.11%)., Conclusion: Additional cytogenetic abnormalities were found in 8% of the sample.

The study was designed to investigate the quantity and reasons of wastage of blood products. This was an observational study conducted from February 2018 to February 2019 at the National Institute of Blood Disease and Bone Marrow Transplantation (NIBD and BMT), PECHS campus. The study was approved by the institutional review board. Wastage and reasons of wastage for all the blood products were evaluated. Frequencies were calculated by using SPSS version 23.0. A total of 2,880 bags of blood products were available, including 960 each of platelets, packed red cells and fresh frozen plasma. The overall wastage rate was 3.5%. Packed red cells and platelets were fully consumed, yet shortage of supply was observed. However, highest wastage was observed in fresh frozen plasma i.e. 102 bags. Expiry of unused products 60 (59%) followed by broken bags 30 (29%) were two common modes of wastage. Wastage of blood products is a genuine issue in a hospital setup, strategies and plan of action should be discussed and implemented to ensure that they are available when and where they are needed most.

Background: Covid-19 spread through blood transfusion has not yet been reported. Despite the prevailing pandemic, there are no recommendations available as yet for testing SARS-CoV-2 antibodies as part of blood screening., Objective: To determine the seroprevalence of SAR-CoV-2 antibodies, its clinical significance and to identify if total antibodies(IgA, IgM, IgG) should be tested or just the specific IgG antibodies only., Method: Consecutive blood donors donated were screened for standard serological panel of HbsAg, Anti-HCV, Anti-HIV and Syphilis using Cobas-411 analyser and Malaria. All seronegative donors were then screened for COVID serology using the same instrument. These results were compared with the blood donors' seroprevalence checked in a cohort in the first week of June 2020. Pre-COVID-19 period (October 2019) blood donors' archived samples were also compared. Donors who were positive on ECLIA were then tested for specific antibodies (IgM or IgG) by ELISA., Results: A total of 380 healthy blood donors were included. All were males with the mean age being 30.6 ± 6.3 years. Ten pre-pandemic samples did not show COVID-19 antibodies, whereas out of 70 samples in the 3rd week of June, only 15 (21.4 %) were positive. However, in July out of the 300 blood donors, 113 (37.7 %) were found to be reactive. To reconfirm our findings, these 113 donors were then tested on ELISA for presence of IgG specifically. Out of these 128 samples, 81 were IgG positive, 23 were borderline positive and 24 were negative., Conclusion: Almost 40 % of blood donors are now seroconverted for COVID-19. This is a reflection of widespread seroprevalence in the adult male population., (Copyright © 2020. Published by Elsevier Ltd.)

Introduction A clear picture of the prevalence of Fanconi anemia is not known due to limited studies and research of the subject. This study will detect the frequency of positive chromosomal breakage in pediatric aplastic patients and provide the evidence-based guidelines which help in consideration of appropriate treatment and awareness to the society. Methods A total of 104 aplastic anemia patients were recruited of age <18 years whose samples were tested for chromosomal breakage with mitomycin C (MMC). History of consanguinity between parents were documented for all the patients referred to us. Result Out of 104 diagnosed aplastic anemia patients, 35 (33.7%) patients were found to be Fanconi positive. Mean age of all hypoplastic patients for aplastic anemia and Fanconi anemia was 10.7 ± 4.5 and 10.6 ± 3.5, respectively. Male preponderance was found to be higher (64, 61.5%) as compared to females (40, 38.5%) in aplastic patients. The male to female ratio was observed as 2.5:1 in Fanconi patients while 1.3:1 in non-Fanconi aplastic patients. Parental consanguinity was observed in 33 (94.2%) with Fanconi anemia. Conclusion Fanconi anemia accounts for significant number of patients with hypoplastic bone marrow, therefore consanguineous marriages should be avoided through mass education in Pakistan., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Siddiqui et al.)

Objective: We performed a prospective analysis at our center to find out the most common organisms causing bacterial infections to establish pattern of antibiotic resistance, in order to combat febrile neutropenia effectively in the terms of outcome as well as cost., Methods: A hospital based observational study was conducted at National Institute of Blood Diseases and bone marrow transplantation from January 2017 to December 2017. Patients presented with absolute neutrophil count (ANC) of less than 500/ml were enrolled. Data were analyzed by SPSS version 21.0. P value of <0.05 was considered statistically significant., Results: In this study, a total of 242 patients from various hematological disorders were enrolled and 403 bacterial isolates were obtained. The most frequent isolated gram-negative organisms were Escherichia coli , followed by Klebsiella pneumoniae and the most prevalent gram-positive organisms were staphylococcus aureus and Enterococcus species . The antimicrobial susceptibility testing revealed that most of the Staphylococcus aureus isolates were highly resistant to methicillin (p=0.002), whereas Enterococcus species were resistant to vancomycin (p=0.000)., Conclusion: The choice of empirical antibiotic regimen should be based on local spectrum of bacteria and their regional susceptibility pattern to improve the survival and minimize hospital stay of patients., Competing Interests: Conflicts of Interest: All authors declare no conflicts of interest., (Copyright: © Pakistan Journal of Medical Sciences.)

Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal disorders of the bone marrow, and are associated with a high disease burden, reduced quality of life (QOL), and shortened survival. This multinational, multicenter, non-interventional registry "MERGE" was initiated with an objective to collect data on the epidemiological indices of classical Ph-MPNs, existing treatment patterns, and impact of MPNs on health-related QOL in various countries/regions in Asia, including the Middle East, Turkey, and Algeria. Of the 884 eligible patients with MPNs, 169 had myelofibrosis (MF), 301 had polycythemia vera (PV), 373 had essential thrombocythemia (ET), and 41 had unclassified MPNs. The median age was 58 years (range, 47-66 years), and 50% of patients were males. The prevalence and incidence of MPNs were estimated to be 57-81 and 12-15 per 100 000 hospital patients per year over the last 4 years, respectively, in these countries. Total symptom score (mean [standard deviation; SD]) at baseline was highest in patients with MF (23.5 [17.47]) compared with patients with ET (14.6 [14.26]) and PV (16.6 [14.84]). Patients with ET had a lower mean (SD) number of inpatient visits (0.9 [0.77] days), and patients with MF had more outpatient visits (5.2 [3.17] days) on an average, compared with the entire MPN group. The study showed that patients with MPNs have a severe disease burden and reduced QOL. A discordance between physician and patient perception of symptom assessment was observed in this study (International clinical trials registry ID: CTRI/2014/05/004598)., (© 2020 The Authors and Novartis Pharma AG. Cancer Medicine published by John Wiley & Sons Ltd.)

Acute myeloid leukemia (AML) is a hematological malignancy characterized by clonal expansion of blast cells that exhibit great genetic heterogeneity. In this study, we describe the mutational landscape and its clinico-pathological significance in 26 myeloid neoplasm patients from a South Asian population (Pakistan) by using ultra-deep targeted next-generation DNA sequencing of 54 genes (∼5000×) and its subsequent bioinformatics analysis. The data analysis indicated novel non-silent somatic mutational events previously not reported in AML, including nine non-synonymous and one stop-gain mutations. Notably, two recurrent somatic non-synonymous mutations, i.e., STAG2 (causing p.L526F) and BCORL1 (p.A400V), were observed in three unrelated cases each. The BCOR was found to have three independent non-synonymous somatic mutations in three cases. Further, the SRSF2 with a protein truncating somatic mutation (p.Q88X) was observed for the first time in AML in this study. The prioritization of germline mutations with ClinVar, SIFT, Polyphen2, and Combined Annotation Dependent Depletion (CADD) highlighted 18 predicted deleterious/pathogenic mutations, including two recurrent deleterious mutations, i.e., a novel heterozygous non-synonymous SNV in GATA2 (p.T358P) and a frameshift insertion in NPM1 (p.L258fs), found in two unrelated cases each. The WT1 was observed with three independent potential detrimental germline mutations in three different cases. Collectively, non-silent somatic and/or germline mutations were observed in 23 (88.46%) of the cases (0.92 mutation per case). Furthermore, the pharmGKB database exploration showed a missense SNV rs1042522 in TP53 , exhibiting decreased response to anti-cancer drugs, in 19 (73%) of the cases. This genomic profiling of AML provides deep insight into the disease pathophysiology. Identification of pharmacogenomics markers will help to adopt personalized approach for the management of AML patients in Pakistan., (Copyright © 2020 Shahid, Shakeel, Siddiqui, Ahmed, Sohail, Khan, Abid and Shamsi.)

Objective: The aim of this study was to assess abnormality of coagulation and anticoagulation parameters in dengue fever patients and the impact of these tests on the management of patients., Background: Dengue fever is endemic in Pakistan with seasonal rise in cases. Morbidities and mortalities are proportionately reported to be increasing and associated with disseminated intravascular coagulation resulting in haemorrhagic or thrombotic manifestations in patients having deranged coagulation profiles., Methods/materials: This observational and descriptive study was conducted on confirmed Dengue patients at the National Institute of Blood Diseases during the years 2013 to 2016. Patients of all age groups were included in this study. Results were analysed by SPSS version 23., Results: A total of 200 patients were selected with the mean age being 28.68 years (±13.28) and male predominance (147/200). The mean platelet count, haemoglobin and haematocrit at base line for bleeders and non-bleeders showed significant results, where platelet count at baseline for bleeders was 24 000, whereas for non-bleeders it was 29 000 and it showed significant correlation with bleeding (P-value .027). Platelets were transfused to 76 (38%) patients. However, none of the specialised haemostasis parameters beside the platelet count correlated with bleeding, requiring platelet transfusions., Conclusion: Our study showed a significant association of platelet counts, haemoglobin and haematocrit with bleeding. It can be concluded that coagulation and anticoagulation profiles will not benefit the management of dengue patients and in countries like Pakistan, it will only add to the economic burden on the patients., (© 2019 British Blood Transfusion Society.)

Objective: In this study, we report acute blood transfusion reactions at our hospital, compare our analysis with the reported data and identify areas for improvement., Background: Haemovigilance programmes have been implemented in many countries, and adverse events associated with blood transfusion are published in their annual reports. Pakistan has no current established programme., Material and Methods: A cross-sectional study was conducted, and all adverse reactions reported to the blood bank from January 2014 to March 2016 were included. An adverse response in the patient, related to administration of blood (within 24 h), was considered an immediate transfusion reaction., Results: During the study period, 20 956 blood components were issued. A total of 32 (0·15%) adverse reactions were documented. Allergic reactions were the most common adverse event observed in 15 (46·8%) of the cases. Febrile non-haemolytic transfusion reaction (FNHTR) was the second most common reaction seen in nine (28%) followed by bacterial contamination in four (12·5%) and acute haemolytic reaction in two (6·2%) of the cases., Conclusion: The low incidence indicates underreporting and the need for a formal haemovigilance system. International benchmarking between different medical systems is helpful to identify areas in the transfusion process that have to be changed to improve transfusion safety., (© 2018 British Blood Transfusion Society.)