Incidence, management and outcome of Hepatic Veno-Occlusive disease /Sinusoidal Obstruction Syndrome after hematopoietic stem cell transplant in Thalassemia major patients: A prospective study of Pakistani BMT.

Objectives: Hepatic Veno occlusive disease (VOD), also known as sinusoidal obstruction syndrome (VOD/SOS), is a post-transplant life threatening complication. In this study, we aimed to discuss the incidence, management and outcome of VOD in post allogenic transplant patients of beta thalassemia major (BTM). Methods: A prospective study was conducted in Armed Forces Bone Marrow Transplant Center, between 2001-2022. A total of 385 fully Human Leucocyte Antigen (HLA) matched BTM patients, with Ursodeoxycholic acid for prophylaxis, were included in the study. Incidence of VOD was calculated through cumulative incidence estimates. Chi square test and Mann Whitney test were used to compare discrete and continuous variables respectively. VOD was diagnosed and graded according to European Society for Blood and Marrow Transplantation EBMT Pediatric diagnostic criteria. Risk factors for VOD were grouped as recipient, transplant and donor related. Univariate analysis was performed by log-rank test. All patients who developed VOD were managed primarily with fluid restriction and strict input output monitoring. Statistical analyses were performed using SPSS v 25.0. Results: Out of 385 transplant patients, forty developed VOD. Median time from date of transplant till onset of VOD was 14 days (range 6-30). Cumulative incidence of all grade VOD was 10.39% (95% CI, 7-14). Eleven out of 40 patients who developed VOD died. Cumulative incidence of Transplant related mortality (TRM) for patients with and VOD was 20.5% (95% CI, 16.6-25.1) vs 27.5% (95% CI, 16.1-42) (p value 0.318) respectively. Among risk factors, age of recipient and fibrosis (p value of 0.04 and 0.000 respectively) were found to be significantly associated with VOD. Conclusions: Careful selection of transplant candidates before transplant can help reduce the incidence of VOD.

Clinical and Lab profile of severe and uncomplicated malaria: A prospective study from Khuzdar Balochistan.

OBJECTIVES: Khuzdar, the largest city of Southern Balochistan, is endemic for malaria with API of 6. The study was aimed at comparing the clinico-lab profile of severe and uncomplicated malaria in the region and to determine any association with age. No such study is reported in the region so far. METHODS: A prospective clinical observational study was conducted in Combined Military Hospital, Khuzdar between 2018 and 2020. A total of 210 Malaria patients, irrespective of age and gender were included. Cases were categorized into severe and uncomplicated according to WHO criteria. The clinical parameters and lab profile of severe and uncomplicated cases were compared and data was analyzed using SPSS 23.0. Categorical variables were analyzed for association of clinical features with severe malaria using Fisher exact test. Continuous variables were compared between uncomplicated and severe malaria using Mann-Whitney U -test. Statistical significance of lab parameters with type of malaria was derived using Kruskal Wallis. RESULTS: Uncomplicated and severe cases were 191 (91%) and 19 (9%) respectively. Severe malaria was significantly associated with jaundice, bleeding from gums, epistaxis, pallor, vomiting, respiratory distress, thrombocytopenia, low Hb, raised serum bilirubin and raised PT (p value<0.05). In children, frequency of multiple complications was significantly higher than adult patients. (75% vs 25%, p-value 0.002).Overall case fatality of severe malaria was 5.2% (1/19). However, case fatality rate was 100% in cerebral malaria. CONCLUSIONS: Certain clinical and lab parameters can be used to predict prognosis and thus avoid adverse outcome in malaria patients.

Ametropia in children with headache.

OBJECTIVE: To measure the frequency of uncorrected ametropia in children with 2 to 8 weeks of persistent headache referred to ophthalmic outpatient department for evaluation. METHODS: This cross sectional study was conducted at CMH Gujranwala from March 2018 to November 2018.A total of 262 children, aged from 5 to 16 years, with 2 to 8 weeks history of persistent headache underwent detailed ophthalmic assessment for refractive errors, and other ophthalmic evaluation. Children with ametropia, confirmed with cycloplegic refraction and post-mydriatic testing were prescribed with glasses. Patients without any ophthalmic findings were referred back to pediatrics department for further evaluation. RESULTS: Mean age of study population was 8.97 ± 3.16 years. Mean duration of headache was 5.03 ± 1.81 weeks. Ametropia was found in 56 (21.4%) children, while 206 (78.6%) had no refractive error. Out of children with ametropia, 20 (35.7%) had myopia, 24 (42.8%) had astigmatism and 12 (21.5%) had hypermetropia. There was no difference in ametropic children and children without ametropia with respect to gender (p=0.73), age (p=0.54) and duration of headache (p=0.71). CONCLUSION: A significant proportion of children with ametropia have initial symptoms of headache. Any child with un-explained headache must undergo ophthalmic evaluation to diagnose refractive error, if any.

Case report: A novel mutation in RTEL1 gene in dyskeratosis congenita.

Dyskeratosis congenita (DKC), also known as Zinsser-Cole-Engman syndrome, is a telomeropathy typically presenting as a triad of leukoplakia, nail dystrophy, and reticular hyperpigmentation. Reported genetic mutations linked to DKC include DKC1, TINF2, TERC, TERT, C16orf57, NOLA2, NOLA3, WRAP53/TCAB1, and RTEL1. Homozygous, compound heterozygous, and heterozygous mutations in RTEL1 (RTEL1, regulator of telomere elongation helicase 1) gene on chromosome 20q13 are known to cause autosomal dominant as well as recessive DKC. Pathogenic variants of RTEL1 gene in DKC patients include c.2288G>T (p. Gly763Val), c.3791G>A (p. Arg1264His), and RTEL p. Arg981Trp. We report a novel homozygous variant of RTEL1, transcript ID: ENST00000360203.11, exon 24, c.2060C>T (p.Ala687Val), in a patient of DKC presenting with leukoplakia, dystrophic nails, reticulate pigmentation, and positive family history of a similar phenotype. The novel variant, reported as a variant of uncertain significance, may therefore be considered diagnostic for DKC in a Pakistani population.

A new species of Lecidea (Lecanorales, Ascomycota) from Pakistan.

We describe here a new species, Lecideaaptrootii, in Lecidea sensu stricto from Swat Valley, Pakistan. It is most similar to L.fuscoatra in having an areolate thallus and black, lecideine apothecia with a persistent margin. However, L.aptrootii can be readily distinguished by having smaller ascospores (average length 8-10 µm). In phylogenetic analyses, using ITS and nuLSU rDNA sequences, L.aptrootii forms a sister-group relationship to L.grisella, which differs in having a rimose thallus.