Role of HRCT in evaluation of Interstitial Lung Disease

In this study, HRCT is the examination technique of choice as it is quickly accomplished, readily available and does not require ancillary studies using other imaging technologies in most cases. In this given study, A total of 40 patients were included in which 16 patients were found to be having ILDs , there were 10 male patients (62.5%) and 6 were female patients i.e., (37.5%) of total number of patients .Idiopathic pulmonary fibrosis were found in 3 (18.75%) patients, Usual interstitial pneumonia in 2 (12.5%) patients, Chronic Hypersensitive pneumonitis in 1 (6.25%) patient , Fibrotic hypersensitive pneumonitis in 4 (25%) patients and Pulmonary interstitial edema in 6 (37.5%). The maximum patients were found in pulmonary interstitial edema and minimum patients in Chronic Hypersensitive pneumonitis, the highest number of patients with interstitial lung disease were from the 60-80 Years age group category, which was 8 Out of 16 i.e. 50% of the total number of the patients and no patients were found from the age group 0-18 years age group and 80-100 years age group.

Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes

Background Body mass index (BMI), a well-known risk factor for poor cardiovascular outcomes, is associated with differential DNA methylation (DNAm). Similarly, metabolic health has also been associated with changes in DNAm. It is unclear how overall metabolic health outside of BMI may modify the relationship between BMI and methylation profiles, and what consequences this may have on downstream cardiovascular disease. The purpose of this study was to identify cytosine-phosphate-guanine (CpG) sites at which the association between BMI and DNAm could be modified by overall metabolic health. Results The discovery study population was derived from three Women’s Health Initiative (WHI) ancillary studies (n = 3977) and two Atherosclerosis Risk in Communities (ARIC) ancillary studies (n = 3520). Findings were validated in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n = 1200). Generalized linear models regressed methylation β values on the interaction between BMI and metabolic health Z score (BMI × MHZ) adjusted for BMI, MHZ, cell composition, chip number and location, study characteristics, top three ancestry principal components, smoking, age, ethnicity (WHI), and sex (ARIC). Among the 429,566 sites examined, differential associations between BMI × MHZ and DNAm were identified at 22 CpG sites (FDR q < 0.05), with one site replicated in MESA (cg18989722, in the TRAPPC9 gene). Three of the 22 sites were associated with incident coronary heart disease (CHD) in WHI. For each 0.01 unit increase in DNAm β value, the risk of incident CHD increased by 9% in one site and decreased by 6–10% in two sites over 25 years. Conclusions Differential associations between DNAm and BMI by MHZ were identified at 22 sites, one of which was validated (cg18989722) and three of which were predictive of incident CHD. These sites are located in several genes related to NF-kappa-B signaling, suggesting a potential role for inflammation between DNA methylation and BMI-associated metabolic health.

Effect of vitamin D on cognitive decline: results from two ancillary studies of the VITAL randomized trial

Low vitamin D levels have been associated with cognitive decline; however, few randomized trials have been conducted. In a trial, we evaluated vitamin D3 supplementation on cognitive decline. We included participants aged 60+ years (mean[SD] = 70.9[5.8] years) free of cardiovascular disease and cancer in two substudies in the VITAL 2 × 2 randomized trial of vitamin D3 (2000 IU/day of cholecalciferol) and fish oil supplements: 3424 had cognitive assessments by phone (eight neuropsychologic tests; 2.8 years follow-up) and 794 had in-person assessments (nine tests; 2.0 years follow-up). The primary, pre-specified outcome was decline over two assessments in global composite score (average z-scores of all tests); substudy-specific results were meta-analyzed. The pooled mean difference in annual rate of decline (MD) for vitamin D3 versus placebo was 0.01 (95% CI − 0.01, 0.02; p = 0.39). We observed no interaction with baseline 25-hydroxyvitamin-D levels (p-interaction = 0.84) and a significant interaction with self-reported race (p-interaction = 0.01). Among Black participants (19%), those assigned vitamin D3 versus placebo had better cognitive maintenance (MD = 0.04, 95% CI 0.01, 0.08, similar to that observed for Black participants 1.2 years apart in age). Thus, vitamin D3 (2000 IU/day cholecalciferol) supplementation was not associated with cognitive decline over 2–3 years among community-dwelling older participants but may provide modest cognitive benefits in older Black adults, although these results need confirmation.Trial registration ClinicalTrials.gov; VITAL (NCT01169259), VITAL-DEP (NCT01696435) and VITAL-Cog (NCT01669915); the date the registration for the parent trial (NCT01169259) was submitted to the registry: 7/26/2010 and the date of first patient enrollment in either of the ancillary studies for cognitive function in a subset of eligible VITAL participants: 9/14/2011.

The Study of Muscle, Mobility, and Aging (SOMMA): An Overview

SOMMA is an NIA-funded cohort study to identify biological determinants of mobility and fitness. The overall aim of SOMMA is to use biopsies, novel biomarkers, advanced imaging, and intensive physical and cognitive assessments to elucidate the biological processes that contribute to changes in mobility and physical fitness with aging. SOMMA will recruit 875 people age 70+ (of whom about 200 have been enrolled.) We take biopsies of the vastus lateralis muscle to quantify mitochondrial content and function of the electron transport chain. We use 31PMR spectroscopy to quantify mitochondrial capacity to generate ATP in quadriceps muscle (ATPmax). We will quantify other biological properties in biopsies including denervation, autophagy and accumulated biochemical damage and use gene expression to discover pathways that contribute to mobility and fitness. SOMMA uses MR for quadriceps volume and D3Cr dilution for total skeletal muscle mass, cardiopulmonary exercise testing to measure fitness (VO2 peak). We are also making many other intensive assessments of physical and cognitive function. Mobility endpoints include baseline and three year change in 400 m and 4 meter gait speed and fitness. SOMMA is building a large biobank of muscle, adipose blood, and urine specimens that will be available for ancillary studies. In this Symposium, we will present results from analyses of associations between muscle mitochondrial function and strength, muscle mass, cognitive performance, gait speed, and fitness. The symposium will also preview opportunities for collaborations and ancillary studies with SOMMA.

Therapy-Related Mixed Phenotype Acute Leukemia: Report of two cases with clinicopathological and molecular data

Introduction/Objective Therapy-related mixed phenotype acute leukemia (Tr-MPAL) is a rare and aggressive disease comprising blast cells of more than one hematopoietic cell lineage. There is limited patient outcome data with this diagnosis. Hence, we present two such cases with clinicopathologic correlation. Methods/Case Report Clinical and pathology data were obtained from institutional electronic health records for two cases of Tr-MPAL identified in the past three years (2018-2020). Results (if a Case Study enter NA) Case 1: 60-years old female, history of chemo-radiotherapy for breast carcinoma, had 49% circulating dimorphic blasts. By immunophenotype, blasts were positive for CD34, CD117, HLA-DR, cCD3, TdT, CD13, CD15, CD38, CD2, CD7, and MPO by cytochemistry, negative for B-cell lineage markers, consistent with Tr-MPAL, T/Myeloid. Ancillary studies revealed normal female karyotype, FLT3-ITD positivity, and DNMT3A frameshift mutation. The patient achieved remission with ALL regimen Hyper-CVAD/methotrexate-cytarabine and underwent an allogeneic stem cell transplant (SCT). The patient was disease-free and on maintenance therapy post 2 years of initial diagnosis. Case 2: 49-years old female, history of chemotherapy for breast carcinoma, had 77% circulating dimorphic blasts (MPO+/PAX5- and MPO-/PAX5+/CD79a+). By immunophenotype, blasts were positive for CD34, CD117, HLA-DR, CD13, CD33, CD15, CD11b, CD19+(dim), cytoCD79a(subset), MPO(subset) and negative for CD14, CD10, CD7, CD8, cCD3, cCD22, and TdT, consistent with Tr-MPAL, B/Myeloid. Ancillary studies revealed normal female karyotype, FLT3-ITD positivity, mutations in RUNX1(frameshift insertion S318fs), SETD2(frameshift insertion P1403fs), WT1(frameshift deletion T377fs), ATM (LI555H), CREBBP (P84S), and DNMT3A (W305). The patient was treated with ALL regimen Hyper-CVAD/methotrexate-cytarabine but relapsed in the post-induction phase with a similar genetics profile. Once remission was achieved, the patient underwent allogeneic SCT and is disease-free while on maintenance therapy post 18 months of initial diagnosis. Conclusion Phenotypically different Tr-MPAL also differ by their underlying genetic abnormalities and may vary in response to therapy. A large cohort of cases may provide us further insights into the genetics and survival outcome of this therapy-related leukemia subtype.

Cellblockistry in serous effusion cytology- A systematic review with recent concepts

Serous effusion cytology being a minimally invasive, readily accessible and inexpensive diagnostic procedure. Nevertheless, the accuracy of SEC could vary widely due to the multitude factors including the level of experience of the cytologists Conventional smear has its own limitations with varied efficacy and hence warranting ancillary studies. Cell block has emerged as a paramount and robust platform for sample processing techniques in cytology. Research studies have proved that the efficiency of cytological diagnosis increases by significant margin of 15-20 percent when it is done in conjunction with cell block techniques especially in cases of exudative fluids in picking up crucial cases and based on this, we intended with a novel aim to analyse the accuracy of Serous effusion cytology by combining conventional smear and cell block technique with an attempt to assess the effectiveness of the cell block by our indigenous Modified Bouin’s method.Cell block method prepared by our indigenous Modified Bouin’s preparation with formalin fixative proved to show high quality significance and hence it could be followed in routine practice across laboratories. Cell block technique is quantitatively superior both standalone as well as in conjunction with conventional smear by improving the effective diagnosis of SEC. Diligent use of cell block technique eliminates the suspicious of malignant category on CS and thereby giving more definite diagnosis and thus it is mandated that combined approach of CB in conjunction with CS should be practiced as binary protocol which proved to have obvious influence on patient management.

Cytology of Undifferentiated Round-Cell Sarcomas of Bone and Soft Tissue: Ewing Sarcoma or Not Ewing Sarcoma , That Is the Question

<b><i>Background:</i></b> Undifferentiated round-cell sarcomas (URCSs) of soft tissue and bone are a group of clinically heterogeneous tumors. Diagnosis of these malignancies is based mainly on recurrent genetic alterations. The most common and the best known representative of this group is Ewing sarcoma (ES) which is characterized by gene fusions including EWSR1 or FUS and ETS transcription factors family. Other newly described entities are CIC-rearranged sarcoma, sarcoma with BCOR genetic alterations, and round-cell sarcoma with EWSR1-non-ETS fusions. All these novel tumors are known as Ewing-like sarcomas. <b><i>Summary:</i></b> It is believed that morphologic features of ES and Ewing-like sarcomas vary only slightly or even that cytomorphology is not relevant. But differences are usually obvious, and some cytologic findings, such as spindle cells, connective tissue fragments, or myxoid stroma, are typical for Ewing-like sarcomas but not for ES. Each of these entities is also characterized by different immunoprofiles. The aim of this review was to summarize cytomorphologic and immunohistochemical features of URCS and compare them with other small round-cell tumors. <b><i>Key Messages:</i></b> Cytology can be successfully used in URCS diagnosis as a complementary tool for core-needle biopsy or even alone in selected cases, especially in recurrent and metastatic tumors. Knowing the morphologic and immunohistochemical differences between URCS is essential to provide appropriate ancillary studies and make a definitive diagnosis.