Frequency and Outcome of Pregnant Females Presenting With Thrombocytopenia at a Tertiary Care Hospital.

BACKGROUND: Platelet-related problems are more frequently discovered in women during pregnancy because screening is carried out as part of the initial clinic examination using automated blood counts. This study was done to find out the frequency and outcomes of pregnant females presenting with thrombocytopenia at a tertiary care hospital. METHODOLOGY: This cross-sectional study was conducted at the Department of Obstetrics and Gynecology, Jinnah Hospital, Lahore, Pakistan, from April 2023 to September 2023. This study involved 280 pregnant women presenting in the third trimester. Blood examination was acquired, and a platelet count less than 150x109/L was labeled as thrombocytopenia. Outcome variables were frequency of thrombocytopenia, while post-delivery, frequency of placental abruption, preterm delivery, stillbirth, need for blood transfusion, and poor Apgar score were noted and compared among women with and without thrombocytopenia. RESULTS: In a total of 280 pregnant females, the mean age and gestational age at the time of presentation were 29.34±4.38 years and 31.30±2.87 weeks, respectively. The mean BMI of the females was 27.97±4.72 kg/m2. Thrombocytopenia was noted in 34 females (12.1%). Placental abruption, preterm delivery, need for blood transfusion, stillbirth, and poor Apgar score were observed in 1.4%, 4.3%, 8.2%, 1.1%, and 2.1% cases, respectively. Placental abruption (11.8% vs. 0.0%; p<0.001), preterm delivery (29.4% vs. 0.8%; p<0.001), need of blood transfusion (35.3% vs. 4.5%; p<0.001), stillbirth (8.8% vs. 0.0%; p<0.001), and poor Apgar score (17.6% vs. 0.0%; p<0.001) were all significantly higher among pregnant women with thrombocytopenia as compared to those with a normal platelet count. CONCLUSION: The frequency of thrombocytopenia was 12.1% among pregnant females. The frequency of placental abruption, preterm delivery, need for blood transfusion, stillbirth, and poor Apgar score were all significantly higher among pregnant women with thrombocytopenia as compared to those with a normal platelet count, irrespective of the patient's age, parity, and BMI.

pyHeart4Fish: Chamber-specific heart phenotype quantification of zebrafish in high-content screens.

Cardiovascular diseases (CVDs) are the leading cause of death. Of CVDs, congenital heart diseases are the most common congenital defects, with a prevalence of 1 in 100 live births. Despite the widespread knowledge that prenatal and postnatal drug exposure can lead to congenital abnormalities, the developmental toxicity of many FDA-approved drugs is rarely investigated. Therefore, to improve our understanding of drug side effects, we performed a high-content drug screen of 1,280 compounds using zebrafish as a model for cardiovascular analyses. Zebrafish are a well-established model for CVDs and developmental toxicity. However, flexible open-access tools to quantify cardiac phenotypes are lacking. Here, we provide pyHeart4Fish, a novel Python-based, platform-independent tool with a graphical user interface for automated quantification of cardiac chamber-specific parameters, such as heart rate (HR), contractility, arrhythmia score, and conduction score. In our study, about 10.5% of the tested drugs significantly affected HR at a concentration of 20 µM in zebrafish embryos at 2 days post-fertilization. Further, we provide insights into the effects of 13 compounds on the developing embryo, including the teratogenic effects of the steroid pregnenolone. In addition, analysis with pyHeart4Fish revealed multiple contractility defects induced by seven compounds. We also found implications for arrhythmias, such as atrioventricular block caused by chloropyramine HCl, as well as (R)-duloxetine HCl-induced atrial flutter. Taken together, our study presents a novel open-access tool for heart analysis and new data on potentially cardiotoxic compounds.

Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants.

The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in the pathogenesis of CAD. We prioritized 220 candidate causal genes, combining eight complementary approaches, including 123 supported by three or more approaches. Using CRISPR-Cas9, we experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility. Our analysis identifies and systematically characterizes >250 risk loci for CAD to inform experimental interrogation of putative causal mechanisms for CAD.

Hereditary hemochromatosis: Temporal trends, sociodemographic characteristics, and independent risk factor of hepatocellular cancer - nationwide population-based study.

BACKGROUND: Hereditary hemochromatosis (HH) has an increased risk of hepatocellular cancer (HCC) both due to genetic risks and iron overload as iron overload can be carcinogenic; HH impacts the increasing risk of HCC, not only through the development of cirrhosis but concerning hepatic iron deposition, which has been studied further recently. AIM: To evaluate HH yearly trends, patient demographics, symptoms, comorbidities, and hospital outcomes. The secondary aim sheds light on the risk of iron overload for developing HCC in HH patients, independent of liver cirrhosis complications. The study investigated HH (without cirrhosis) as an independent risk factor for HCC. METHODS: We analyzed data from National Inpatient Sample (NIS) Database, the largest national inpatient data collection in the United States, and selected HH and HCC cohorts. HH was first defined in 2011 International Classification of Disease - 9th edition (ICD-9) as a separate diagnosis; the HH cohort is extracted from January 2011 to December 2019 using 275.01 (ICD-9) and E83.110 (ICD-10) diagnosis codes of HH. Patients were excluded from the HH cohort if they had a primary or secondary diagnostic code of cirrhosis (alcoholic, non-alcoholic, and biliary), viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH). We removed these patients from the HH cohort to rule out bias or ICD-10 diagnostic errors. The HCC cohort is selected from January 2011 to December 2019 using the ICD-9 and ICD-10 codes of HCC. We selected a non-HCC cohort with the 1:1 fixed ratio nearest neighbor (greedy) propensity score method using the patients' age, gender, and race. We performed multivariate analysis for the risk factors of HCC in the HCC and non-HCC matched cohort. We further analyzed HH without cirrhosis (removing HH patients with a diagnosis of cirrhosis) as an independent risk factor of HCC after adjusting all known risk factors of HCC in the multivariate model. RESULTS: During the 2011-2019 period, a total of 18031 hospitalizations with a primary or secondary diagnosis of HH (excluding liver diseases) were recorded in the NIS database. We analyzed different patients' characteristics, and we found increments in inpatient population trend with a Ptrend < 0.001 and total hospital cost of care trend from $42957 in 2011 to $66152 in 2019 with a Ptrend < 0.001 despite no change in Length of Stay over the last decade. The multivariate analyses showed that HH without cirrhosis (aOR, 28.8; 95%CI, 10.4-80.1; P < 0.0001), biliary cirrhosis (aOR, 19.3; 95%CI, 13.4-27.6; P < 0.0001), non-alcoholic cirrhosis (aOR, 17.4; 95%CI, 16.5-18.4; P < 0.0001), alcoholic cirrhosis (aOR, 16.9; 95%CI, 15.9-17.9; P < 0.0001), hepatitis B (aOR, 12.1; 95%CI, 10.85-13.60; P < 0.0001), hepatitis C (aOR, 8.58; 95%CI, 8.20-8.98; P < 0.0001), Wilson disease (aOR, 4.27; 95%CI, 1.18-15.41; P < 0.0001), NAFLD or NASH (aOR, 2.96; 95%CI, 2.73-3.20; P < 0.0001), alpha1-antitrypsin deficiency (aOR, 2.10; 95%CI, 1.21-3.64; P < 0.0001), diabetes mellitus without chronic complications (aOR, 1.17; 95%CI, 1.13-1.21; P < 0.0001), and blood transfusion (aOR, 1.80; 95%CI, 1.69-1.92; P < 0.0001) are independent risk factor for liver cancer. CONCLUSION: Our study showed an increasing trend of in-hospital admissions of HH patients in the last decade. These trends were likely related to advances in diagnostic approach, which can lead to increased hospital utilization and cost increments. Still, the length of stay remained the same, likely due to a big part of management being done in outpatient settings. Another vital part of our study is the significant result that HH without cirrhosis is an independent risk factor for HCC with adjusting all known risk factors. More prospective and retrospective large studies are needed to re-evaluate the HH independent risk in developing HCC.

Celiac Disease Patients With Coronary Artery Disease: A Nationwide Population-Based Study.

Background Coronary artery disease (CAD) is associated with celiac disease (CD) with limited evidence. However, the common risk factors linking CD and CAD are still lacking in the literature. Known CAD risk factors include hypertension, hyperlipidemia, type 2 diabetes, obesity, and tobacco use. Common risk factors linking CD and CAD are poorly documented. Objective There are three objectives: Firstly, to evaluate potential demographic differences between CD patients with CAD and without CAD. Secondly, to analyze the risk factors of CAD in CD patients. Lastly, to compare CD-CAD and matched non-CD CAD to determine whether there are additional CAD risks in individuals with CD. Methods The study is a nationwide retrospective case-control study. The National Inpatient Sample (NIS) database was used to identify patients admitted between 2016 and 2018 with a principal or secondary diagnosis of CD. We analyzed sociodemographic and clinical risk factors of CAD in CD patients and compared the CD-CAD population with the matched non-CD CAD cohort. Results Out of 23,441 hospitalizations with CD in 2016-2018, 4244 (18%) were found to have CAD. Established CAD risk factors identified in CD patients included hypertension, hyperlipidemia, type 2 diabetes, and a family history of CAD. In contrast, tobacco use is not a CAD risk factor in CD patients. Female patients with CD had 55% lesser odds of CAD than male patients. The odds of CAD in CD patients with hyperlipidemia were five times higher, 1.2 times higher with essential hypertension, and two times higher with type 2 diabetes. Patients with CAD had a higher prevalence of iron deficiency anemia (9.33% CD-CAD and 8.28% non-CAD CD Vs. 7.32% non-CD CAD). Conclusions Our study confirms that, as with non-CD individuals, males and the White race are at increased CAD risk in the CD population. CD-CAD patients have a higher hyperlipidemia prevalence than non-CD CAD patients. CD patients with type 1 diabetes have an early diagnosis of CAD compared to CD patients with type 2 diabetes. Iron deficiency anemia is a statistically significant risk factor for CAD in CD patients.

The Spectrum of Malignant Neoplasms among Liver Transplant Recipients: Sociodemographic Factors, Mortality, and Hospital Burden.

Objective: To determine the nationwide prevalence of malignant neoplasms (excluding hepatocellular carcinoma-HCC) in hospitalized liver transplant recipients and to study the hospital utilization, and mortality to the incidence of malignancies. To the best of our knowledge, few epidemiological studies addressed outcomes in post-liver transplant patients, such as the annual number of hospitalizations, mortality, patient characteristics regarding malignancies. Methods: NIS database was queried between 2016 and 2018 to retrieve records of patients admitted with a principal or secondary diagnosis of liver transplant following the International Classification of Diseases, tenth Revision (ICD-10). The population was divided into case and control groups according to the presence and absence of malignant neoplasm (MN) except for HCC. We also compared the incidence of MN in LTX patients and non-LTX matched cohort. Results: A total of 7.28% admissions were associated with malignant neoplasms (except HCC) in LTX patients. Lymphomas, respiratory, gastrointestinal (excluding HCC), leukemia, and head/neck were commonest cancers with estimated admission rates of 0.97%, 0.90%, 0.80%, 0.53%, and 0.49%, respectively. Lung cancer was the most frequent malignant neoplasm among White and Black racial/ethnic groups (15.78% and 14.8%), whereas lymphoma was pervasive among Hispanics (20.3%). Lung cancer had the highest in-hospital mortality (10.55%), followed by the cancer of the nervous system (9.09%). The LTX and non-LTX cohort comparison showed that LTX patients are at increased risk of head and neck cancers, skin cancers, lymphomas, tumors, and Myelodysplastic syndrome. According to a multivariate analysis, a statistically significant association existed between malignant neoplasms in LTX patients and the following factors: increasing age (P < .001), higher mortality (P < .001), females with 29% lesser odds than males (P < .001), Black race and Hispanic ethnicity with 20% and 26% lesser odds as compared to White (P < .05). Clinical factors included smoking, Alcoholic cirrhosis, Hepatitis B, and Hepatitis C, were statistically significant risk factors of post-liver transplantation malignancies. Conclusions: Malignancies were frequent among elderly patients and predominantly in males. Lymphoproliferative diseases were the most prevalent malignancy types, followed by respiratory/lung cancer- which showed the highest mortality risk of all cancers. LTX patients are at increased risk of head and neck cancers, skin cancers, lymphoma, tumors, and Myelodysplastic syndrome compared to non-LTX patients.