Lid wiper epitheliopathy in symptomatic and asymptomatic dry eye subjects.

PURPOSE: Lid wiper epithliopathy (LWE) was stuided in symptomatic and asymptomatic dry eye subjects. This is the first such study to be conducted in the Indian population. LWE is a clinical condition associated with vital staining in the lower and upper eyelids on increased friction of the lid margin over to the cornea. Our aim was to study LWE in symptomatic and asymptomatic (control) dry eye subjects. METHODS: Out of 96 subjects screened, 60 subjects were enrolled in the study and were divided into two groups, symptomatic and asymptomatic dry eye subjects, based on the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire and the Ocular Surface Disease Index (OSDI) scores. The subjects were examined to rule out clinical dry eye findings and assessed for LWE with two different dyes (fluorescein and lissamine green). Descriptive analysis was done and Chi-square test was used for statistical analysis. RESULTS: A total of 60 subjects were enrolled in a study with a mean age of 21.33 ± 1.88 years, out of which the majority of LWE patients (99.8%) was seen in the symptomatic group than the asymptomatic group (73.3%); the difference was statistically significant (p = 0.00) and also clinically significant. LWE was found to be significantly higher in symptomatic dry eye subjects (99.8%) compared to asymptomatic dry eye subjects (73.3%). LWE severity was also found to be more (56.6% of grade 3) among symptomatic dry eye subjects compared to asymptomatic subjects (40% of grade 2). CONCLUSION: It is important to assess the lid wiper region (LWR) and treat LWE in routine clinical practice.

Spectrum of Chromosomal Abnormalities Detected by Conventional Cytogenetic Analysis Following Invasive Prenatal Testing of Fetuses with Abnormal Ultrasound Scans.

Objectives: The frequent association between malformations and chromosomal abnormalities is now well-established. This study looks at the incidence and type of chromosomal abnormalities detected by conventional cytogenetic analysis in women undergoing invasive tests following detection of fetal anomalies on antenatal scans as well as incidence of other genetic abnormalities detected by DNA analysis of fetuses with congenital anomalies that had a normal karyotype. Materials and Methods: A retrospective, observational study of pregnant women undergoing invasive testing following identification of fetal anomalies by ultrasonography was carried out in a tertiary care facility, Vellore, India, between 2011 and 2018. Results: 169 women underwent an invasive diagnostic procedure following detection of fetal anomalies. The most common indication for doing fetal karyotype was the presence of major fetal structural anomalies (142/169, 84%) with over a third (48/142, 34%) having multisystem involvement. Fetal hydrops was the next most common indication, detected in 18/169 (10%) fetuses. Aneuploidy was seen 19 of 25 fetuses (76%) with an abnormal karyotype with autosomal aneuploidy accounting for 13 (68%) and sex chromosome aneuploidy for seven (37%) of the fetuses. One fetus had double aneuploidy. In fetuses with normal karyotype, no additional information was obtained from further genetic testing. Conclusions: The overall detection rate of chromosomal abnormalities in our study using conventional cytogenetic analysis was 14.8%, the majority (72%) being associated with structural malformations, 20% with non-immune hydrops and 4% with soft markers. Abnormal karyotypes were seen in 12.7% of fetuses with structural malformations.

High Counts in Hematologic Malignancies Predict Low Metaphase Yield for Cytogenetic Analysis.

OBJECTIVES: This study examined the impact of various preanalytical variables on metaphase yield in hematologic malignancies. METHODS: Marrow samples from patients with hematologic malignancies that were subjected to cytogenetic analysis were categorized into two groups: one with samples that yielded an adequate number of metaphases, defined as at least 20, and a second with a low number of metaphases (LNM), having fewer than 20 metaphases. Age, sex, bone marrow nucleated cell (MNC) count, and peripheral blood counts (hemoglobin, total WBC count, and platelet count) were analyzed for an association with LNM. RESULTS: Of 455 samples, 17% (79/455) belonged to the LNM group, including 6% (27/455) that yielded no metaphases. MNCs and WBCs were higher in the LNM group (P < .001 for both). MNCs were higher in LNM groups in both acute myeloid leukemia (P = .008) and acute lymphoblastic leukemia (P = .001). Receiver operating characteristic curves showed moderate prediction of MNC and WBC counts for LNM with areas under the curves of 0.7. Other analyzed parameters showed no significant associations with LNM. CONCLUSIONS: Low metaphase yields occur frequently in hematologic malignancies with high counts. This could reflect biological characteristics of these malignancies that merit further investigation.

Single nucleotide polymorphism array versus karyotype for prenatal diagnosis in fetuses with abnormal ultrasound: A systematic review and meta-analysis.

OBJECTIVE: To estimate the incremental yield of single nucleotide polymorphism (SNP) array over karyotype and to assess the diagnostic accuracy of SNP array as a stand-alone test versus SNP array with karyotype in detecting chromosomal abnormalities for prenatal diagnosis in women with an abnormal fetal ultrasound. STUDY DESIGN: Studies in which SNP array and karyotype had been used for diagnosing chromosomal aberrations in fetuses with abnormal ultrasound findings were included. A systematic search of relevant studies published in the English language in EMBASE, PubMed, CENTRAL, CDSR (Cochrane database of systematic reviews), SCOPUS and Web of science between 1996 and May 2020 was performed. Primary outcome was incremental yield of SNP array over karyotype (number of patients with abnormalities detected by SNP array over number of patients with normal karyotype). Other outcomes included diagnostic accuracy of SNP array alone versus SNP array and karyotype for prenatal diagnosis. Pooled sensitivities, specificities, and their 95% confidence intervals (CI) were presented. RESULT(S): Seven studies were included. The incremental yield of SNP array over karyotype was 8% (95% Confidence interval, CI 4-12%) while incremental yield of karyotype over SNP array in foetus with abnormal ultrasound was 0% (95% CI 0-1%). The agreement between SNP array and karyotype was 92%. The variant of unknown significance rates ranged between 4 and 8 %. The pooled sensitivity and specificity of SNP array versus SNP array and karyotype was 0.97 (95% CI 0.92-0.99) and 1.00 (95% CI1.00-1.00), respectively. CONCLUSION(S): SNP array provides additional information on chromosomal abnormalities over and above conventional karyotype. When used as a stand-alone test, SNP array performs favourably as a diagnostic modality when compared against SNP array and karyotype for prenatal diagnosis with an abnormal fetal ultrasound.

Utility of Chromosomal Microarray in Children with Unexplained Developmental Delay/Intellectual Disability.

ObjectiveTo evaluate the chromosomal microarray (CMA) yield among children who presented with global developmental delay/intellectual disability (GDD/ID) with/without co-occurring conditions. Methods: The pathogenic copy number variation (pCNVs) findings on CMA of all children who presented with unexplained GDD/ID were categorized based on the clinical features. The karyotype results were compared with CMA. Results: The overall pCNV yield in children presenting with GDD/ID with or without comorbid conditions constituted 20.9%. Among the 17 pCNVs, 13 were losses and four were gains. Cardiac defect was the only co-morbidity in our study that demonstrated statistically significant prediction for pCNV (odds ratio 6.13, p value- 0.031). Six children who were karyotyped prior to CMA testing showed a structural abnormality. Conclusions: In our study, 20.9% of children with GDD/ID showed pCNVs on CMA. Cardiac defect alongside GDD/ID, emerged as the single strongest phenotype associated with pCNVs. CMA also provided vital information in previously karyotyped patients.

Turner Syndrome and Craniopharyngioma.

Turner syndrome (TS) affects nearly 1 in 2000 live births (1) and craniopharyngioma, a benign brain tumor, has been reported to occur at an incidence of 1.3 per million (2). These rare disorders are not known to coexist. The authors report a patient with incidental suprasellar mass who was diagnosed with both craniopharyngioma and TS, a rare association.

Non-invasive Prenatal Testing in Pregnancies Following Assisted Reproduction.

In the decade since non-invasive prenatal testing (NIPT) was first implemented as a prenatal screening tool, it has gained recognition for its sensitivity and specificity in the detection of common aneuploidies. This review mainly focuses on the emerging role of NIPT in pregnancies following assisted reproductive technology (ART) in the light of current evidence and recommendations. It also deals with the challenges, shortcomings and interpretational difficulties related to NIPT in ART pregnancies, with particular emphasis on twin and vanishing twin pregnancies, which are widely regarded as the Achilles' heel of most pre-natal screening platforms. Future directions for exploration towards improving the performance and extending the scope of NIPT are also addressed.

The t(8;14)(q24.1;q32) and its variant translocations: A study of 34 cases.

BACKGROUND: The t(8;14)(q24.1;q32) and its variants - the t(2;8)(p12;q24.1) and t(8;22)(q24.1;q11.2) are associated with B-cell neoplasia and result in MYC/immunoglobulin (IG) gene rearrangement. PATIENTS AND METHODS: We correlated the cytogenetic, molecular and clinico-pathological findings of patients with 8q24 translocations seen in the Department of Haematology, Christian Medical College, Vellore, from January 2003 to December 2015. RESULTS: There were 34 patients with 8q24 translocations (31, ALL and three myeloma). The t(8;14) was seen in 25 patients, t(8;22) in seven and t(2;8) in two. The salient findings were as follows: 85% males; 79% adults, median age 37 years; L3 morphology in 61%; mature B immunophenotype in 77%; extra-medullary disease in 41%; additional abnormalities in 28 (85%), notably, structural abnormalities of chromosome 1q (41%) and 13q (9%) and monosomy 13 (15%); complex karyotypes in 68%. There were two double-hit lymphoma/leukemia, one with a t(14;18)(q32;q21) and the other with a t(3;14)(q27;q11.2), associated with nodal high grade B cell lymphoma and dermal leukemic infiltrates respectively. Only 13 samples were processed for DNA PCR and all these samples were positive for MYC-IgH (c-gamma type) rearrangement. Only in one patient, in addition to c-gamma, c-alpha rearrangement was also detected. CONCLUSION: The frequency (1.7%) and distribution of these translocations in our series and the association with 1q and 13q abnormalities is similar to the literature. Trisomies 7 and 12 were seen in less than 10% of our patients.

MYH9-related disorder, a probable May-Hegglin anomaly case series: A tertiary care experience.

OBJECTIVE/BACKGROUND: May-Hegglin anomaly (MHA) is a rare familial bleeding disorder characterized by a triad of thrombocytopenia, giant platelets, and Döhle-like inclusion bodies within the leukocytes. The clinical spectrum as well as the pathophysiology of this entity is not well defined. The objective of this work is to present a series of three cases of MHA diagnosed in our hospital, where the patients presented with variable bleeding manifestations, thrombocytopenia, and giant platelets. MATERIALS AND METHODS: We studied three cases of possible MHA. In addition to the clinical examination, complete hemogram, and peripheral blood smear examination, these patients were also subjected to coagulation studies. Although bleeding symptoms varied among these patients, platelet aggregation tests with various agonists showed a normal response. RESULTS: Consistent findings of this entity noted in our patients were mild-to-moderate thrombocytopenia, giant platelets, and Döhle-like inclusions within the leukocytes. CONCLUSION: A diagnosis of MHA could be made based on a thorough peripheral blood smear examination, which also helps to avoid a misdiagnosis of immune thrombocytopenia.

Comparison of newly diagnosed and relapsed patients with acute promyelocytic leukemia treated with arsenic trioxide: insight into mechanisms of resistance.

There is limited data on the clinical, cellular and molecular changes in relapsed acute promyeloytic leukemia (RAPL) in comparison with newly diagnosed cases (NAPL). We undertook a prospective study to compare NAPL and RAPL patients treated with arsenic trioxide (ATO) based regimens. 98 NAPL and 28 RAPL were enrolled in this study. RAPL patients had a significantly lower WBC count and higher platelet count at diagnosis. IC bleeds was significantly lower in RAPL cases (P=0.022). The ability of malignant promyelocytes to concentrate ATO intracellularly and their in-vitro IC50 to ATO was not significantly different between the two groups. Targeted NGS revealed PML B2 domain mutations in 4 (15.38%) of the RAPL subset and none were associated with secondary resistance to ATO. A microarray GEP revealed 1744 genes were 2 fold and above differentially expressed between the two groups. The most prominent differentially regulated pathways were cell adhesion (n=92), cell survival (n=50), immune regulation (n=74) and stem cell regulation (n=51). Consistent with the GEP data, immunophenotyping revealed significantly increased CD34 expression (P=0.001) in RAPL cases and there was in-vitro evidence of significant microenvironment mediated innate resistance (EM-DR) to ATO. Resistance and relapse following treatment with ATO is probably multi-factorial, mutations in PML B2 domain while seen only in RAPL may not be the major clinically relevant cause of subsequent relapses. In RAPL additional factors such as expansion of the leukemia initiating compartment along with EM-DR may contribute significantly to relapse following treatment with ATO based regimens.

Pseudothrombocytopenia observed with ethylene diamine tetra acetate and citrate anticoagulants, resolved using 37°C incubation and Kanamycin.

Pseudothrombocytopenia (PTP) is defined by falsely low platelet counts on automated analyzers caused by in vitro phenomena including large platelet aggregates in blood samples. Diagnosis and resolution of PTP is crucial as it can lead to unwarranted interventions. We discuss a case of PTP in a pre-surgical setting, which was resolved using 37°C incubation and Kanamycin.