Belantamab mafodotin (belamaf), an antibody-drug conjugate approved for the treatment of relapsed and refractory multiple myeloma (RRMM), is an anti B-cell maturation antigen (BCMA) agent. DREAMM-1, a first in-human trial of belamaf, reported several ocular toxicities requiring dose adjustments, dose delays and treatment discontinuations. In DREAMM-1, 53% of patients in part-1 and 63% of patients in part-2 had ocular toxicity. Similarly, 73% of patients in DREAMM-2 had keratopathy (71% in 2.5 mg/kg versus 75% in 3.4 mg/kg) with the most common symptoms being blurred vision and dry eyes. Ocular toxicity of belamaf is attributed to microtubule-disrupting monomethylauristatin-F (MMAF), a cytotoxic payload of the drug that causes an off-target damage to the corneal epithelial cells. Ocular adverse events (AEs) of belamaf are more frequent at higher doses compared with lower doses. Higher belamaf dose, history of dry eyes and soluble BCMA are associated with increased risk of corneal toxicity. Absence of ocular symptoms does not exclude the possibility of belamaf-induced ocular toxicity, so patients need slit lamp and Snellen visual acuity testing to detect microcytic-like epithelial changes and visual decline. Corticosteroid eyes drops for 4-7 days prior to belamaf dose do not prevent ocular AEs and may cause steroid-related AEs instead. Keratopathy and Visual Acuity scale (KVA) is recommended to document the severity of belamaf-induced ocular toxicity and make treatment adjustments. Management of toxicity includes dosage modifications, treatment interruption or discontinuations and preservative-free artificial tears along with close ophthalmology and hematology-oncology follow-ups.

Hypocupremia due to zinc products can cause sideroblastic anemia and neutropenia and mimics other serious hematological disorders. Early consideration of the copper deficiency and a thorough clinical history can prevent unnecessary interventions.

Beta-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. 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. 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, with initial search retrieved 981 studies. Among these, 166 studies met the inclusion criteria, and only 14 studies met the final criteria for qualitative synthesis. Analysis of 14 studies (n = 3786) showed 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 that reported HIV seroprevalence of 0% and 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 an HCV rate of 22% compared to only 8.4% in patients younger than ten years of age. A comparison of HCV in healthy donors vs. thalassemia patients showed a rate of 1.9% vs. 13.1% for TM patients. 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. Our study highlights that the prevalence of transfusion-transmitted infections, especially HCV, is alarmingly higher (26%) in the TM population than in the general population. There is limited data regarding the prevalence of HIV, syphilis, and malaria in this population. This is mainly due to a fragmented system of blood transfusion, weak regulations, and lower rates of voluntary blood donations. These findings warrant better health measures to improve the blood donation system and specialized care for TM patients.

The dental abnormalities are the typical features of many ectodermal dysplasias along with congenital malformations of nails, skin, hair, and sweat glands. However, several reports of non-syndromic/isolated tooth agenesis have also been found in the literature. The characteristic features of hypohidrotic ectodermal dysplasia (HED) comprise of hypodontia/oligodontia, along with hypohidrosis/anhidrosis, and hypotrichosis. Pathogenic variants in EDA, EDAR, EDARADD, and TRAF6, cause the phenotypic expression of HED. Genetic alterations in EDA and WNT10A cause particularly non-syndromic/isolated oligodontia. In the current project, we recruited 57 patients of 17 genetic pedigrees (A-Q) from different geographic regions of the world, including Pakistan, Egypt, Saudi Arabia, and Syria. The molecular investigation of different syndromic and non-syndromic dental conditions, including hypodontia, oligodontia, generalized odontodysplasia, and dental crowding was carried out by using exome and Sanger sequencing. We have identified a novel missense variant (c.311G>A; p.Arg104His) in WNT10A in three oligodontia patients of family A, two novel sequence variants (c.207delinsTT, p.Gly70Trpfs*25 and c.1300T>G; p.Try434Gly) in EDAR in three patients of family B and four patients of family C, respectively. To better understand the structural and functional consequences of missense variants in WNT10A and EDAR on the stability of the proteins, we have performed extensive molecular dynamic (MD) simulations. We have also identified three previously reported pathogenic variants (c.1076T>C; p.Met359Thr), (c.1133C>T; p.Thr378Met) and (c.594_595insC; Gly201Argfs*39) in EDA in family D (four patients), E (two patients) and F (one patient), correspondingly. Presently, our data explain the genetic cause of 18 syndromic and non-syndromic tooth agenesis patients in six autosomal recessive and X-linked pedigrees (A-F), which expand the mutational spectrum of these unique clinical manifestations.

Vitamin D (Vit-D) plays a central role in calcium homeostasis and maintains skeletal integrity. Housewives in Quetta, Pakistan are at increased risk of vitamin D deficiency (VDD). They spend a greater part of their day in cleaning, washing, cooking, managing daily groceries, and other household chores. Thus, little time is left for self-care and outdoor activities. They wear hijab and have very little exposure to sunlight. In addition, their diet is deficient in Vit-D-rich food items, rendering them at high risk of VDD. Fear of getting tanned, melasma, and preference for a fair complexion further limit their sun exposure. This study evaluates the prevalence of VDD in housewives and determines its various risk factors to recommend screening guidelines for VDD. A cross-sectional study was performed between November 2020 and April 2021 and recruited housewives aged >18 from the outpatient department of a tertiary care hospital in Quetta. Informed consent was obtained from all participants. VDD was defined as a serum 25(OH)-D level <20 ng/mL (50 nmol/L). Sociodemographic variables and information about the dietary habits, perception, attitudes towards sunlight, and daily duration of sunlight exposure were collected. Mean and standard deviation (SD) were calculated for continuous variables and counts, and proportions were calculated for categorical variables like education, age. Univariate and multivariate logistic regression analyses were performed to determine the risk factors and associations of VDD. Data were analyzed by SAS/STAT software (version 9.4). Among 151 housewives, 58.9% of housewives had VDD. VDD group had a higher proportion of females aged 18-30 years and a lower proportion of graduates. The reported use of Vit-D supplements was much lower in the VDD group compared with the non-deficient group, 38.2% versus 71.0 %, P-value <0.001. History of fragility fractures was reported by 10.1% of housewives in the VDD group compared to 4.8% in the non-deficient group, P-value: 0.03. Around 77.5% of housewives in the VDD group spent 15 minutes or less outdoors versus 51.6% in the non-deficient group; 55.1% of housewives in the VDD group reported that they never consumed milk versus 17.7 % in the non-deficient group, P-value <0.00001. In the univariate logistic regression model, housewives with an 11-12th grade of education had 4.80-fold higher odds of VDD compared to those who had undergraduate or graduate degrees (OR: 4.80, 95 % CI: 1.07-21.45). Housewives who never consumed milk had 9.72-fold (95 % CI: 3.69-25.58) higher odds of VDD compared to those who consumed milk on daily basis. Odds of VDD were 3.61-fold (95% CI: 1.06-12.31) higher in those who never consumed fish as compared to those who ate fish at least 1-2 days/week. In multivariate logistic regression, age group 18-30 (OR: 17.07, 95% CI: 1.18-246.86), and never consuming milk (OR: 7.33, 95 % CI: 1.99-26.89) were independently associated with VDD. VDD is highly prevalent (58.9%) in housewives of Quetta. It is the need of time to increase awareness regarding the health benefits, sources, and deficiency symptoms of Vit-D. Our study revealed VDD in housewives irrespective of education and income. Dietary supplementations were greater predictors of VDD. Daily sun exposure should be encouraged, and food items should be fortified with Vit-D. Recommendations for Vitamin D screening would be a good step, especially in Muslim housewives.

Inflammatory fibroid polyps (IFPs) are rare mesenchymal lesions that can arise throughout the gastrointestinal tract. These tumors represent less than 0.1% of all gastric polypoid lesions and are frequently found incidentally on endoscopic evaluation. While presenting symptoms depend on the location of the tumor, gastric polyps commonly present with epigastric pain and early satiety. We hereby delineate the case of a middle-aged female who presented with chronic iron deficiency anemia and a positive fecal occult blood test. She underwent an upper endoscopy, which revealed an actively oozing umbilicated lesion in the gastric antrum. Endoscopic ultrasound divulged the submucosal origin of the lesion. It was subsequently excised using endoscopic mucosal resection. Pathologic examination of the resected specimen confirmed the diagnosis of gastric IFP. Furthermore, we conducted a systematic literature search of the MEDLINE database centered on gastric IFPs from January 2000 till March 2020. The data on patient demographics, clinical features, endoscopic findings, lesion site and size, and treatment approaches were collected and analyzed. This article illustrates the overarching need for clinicians to be vigilant of gastric IFPs presenting with initial clinical symptoms suggestive of occult upper gastrointestinal bleeding. Prompt diagnosis and management of gastric IFPs carry paramount importance to combat chronic unexplained iron deficiency anemia following occult bleeding in such patients. A concoction of endoscopy, biopsy, and immunohistochemical examination can be employed toward their prompt detection. Although gastric IFPs have conventionally been treated with surgery, endoscopic resection is now emerging as a safe and efficient therapeutic modality.