In Celiac disease: Type 3a, 3b and grade BI is more frequent on Marsh Modified (Oberhuber) / Corraza classification.

Introduction: Histopathological alterations in celiac disease (CD)are villous atrophy, intraepithelial lymphocyte infiltration and crypt hyperplasia. It is caused by gluten in genetically predisposed persons. Duodenum and proximal part of jejunum are most commonly involved. Various classifications are used to define histopathological features of CD, but it is easier to define on Marsh modified (Oberhuber) Corraza classification. Objective: The object of study is to differentiate histopathogical feature of celiac disease on Marsh modified (Oberhuber) and Corraza classifications Methodology: This retrospective study of 66 cases of CD carried out at Muhammad Medical college Mirpurkhas Sindh Pakistan between January 2016 to December 2017. Fresh slides prepared and dually observed. All observations denoted and systemized on Marsh modified (Oberhuber) Corraza classification. There are many mimics of CD, they should be excluded for the proper approach to diagnosis.  Conclusion:  Histopathogical finding are helpful in CD if they are carefully classified. Typing and grading system of Marsh modified Corraza classification is easier to define and is supportive to observe the features in diagnosis and prognosis of disease.   Key words:  Celiac disease, Intraepithelial lymphocytes, villous atrophy. Histopathology, serolog

Management of the Triple Negative Locally Advanced Breast Cancer

One out of eight women is suffering from the breast cancer. 2.3 million New cases is predicted by 2023 worldwide. Triple negative breast cancer (TNBC) is having 10–15% incidence. As categorized with the lack of estrogen, progesterone and human epidermal growth factor receptor 2 neu receptor expression. Though it presents with narrow management opportunities that makes it to be the poor prognostic as well as survival rate. The management of the TNBC includes: neoadjuvant treatment then surgery and the adjuvant treatment or the surgery as the first step and then the adjuvant treatment options accordingly. The discussion are still going on to set a management protocol for the triple negative breast cancers with positive outcome and the good disease free survival. Neoadjuvant or adjuvant chemotherapy decreases the estradiol levels and thus improves the survival. The immune check points and immune modulators are under the research and the trials are still going on to treat the TNBC with the improved outcomes. It has been concluded that the management of the TNBC, still wanting the guidelines as tumor-specific targeted therapies is in trials

Clinico-Pathological Findings in Myeloid Malignancies: A Single Center Experience

INTRODUCTION: Myeloid malignancies are clonal disorders of hematopoietic stem/precursor cells. The criteria for the diagnosis of acute myeloid leukemia (AML) are based on morphological cytogenetic and flow-cytometric findings. The prognostic outcome with intensive chemotherapy is better than with non-intensive treatment. PURPOSE/OBJECTIVES: To determine the frequency of various clinical & pathological findings in myeloid malignancies. STUDY DESIGN: Cross sectional descriptive study. PLACE AND DURATION OF STUDY: The study was carried out at Department of Pathology from October 2014 to December 2016. MATERIAL/PATIENTS AND METHODS: Detailed history, clinical and pathological findings recorded on a pre-designed proforma including bone marrow reports was evaluated. RESULTS: During period of study, 351 proformas including bone marrow reports were evaluated, from which 49 (30 males and 19 females; age ranges between 03 months to 60 years) were diagnosed as myeloid malignancies. The distribution of myeloid malignancies were acute myeloid leukemia (n=21), chronic myeloid leukemia (n=14), acute myelodysplastic syndrome (n=3), myeloproliferative neoplasms (n=3), myelofibrosis (n=2), myeloid hyperplasia (n=2), acute promyelocytic leukemia (n=2), myelomonocytic leukemia (n=1), ,and transient abnormal myelopoiesis (n=1).The main presenting complaints were fever and weight loss, whereas splenomegaly was the most common finding on clinical examination. The commonest laboratory finding was anemia followed by leukocytosis; while 10 patients showed pancytopenia. CONCLUSION: AML with fever and bicytopenia is the commonest myeloid malignancy in our series

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Multiple loci on 8q24 associated with prostate cancer susceptibility

Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. To identify common PrCa susceptibility alleles, we have previously conducted a genome-wide association study in which 541, 129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and 1,894 controls. We have now evaluated promising associations in a second stage, in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls, and a third stage, involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to previously identified loci, we identified a further seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11, and 22 (P=1.6×10−8 to P=2.7×10−33)

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p<0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p<0·0001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status