History Of Disease Research Articles

Caseous Calcification of the Mitral Annulus: Calcified Toothpaste of the Heart.

Caseous calcification of the mitral annulus (CCMA) is a rare variant of mitral annular calcification (MAC) usually described as an antemortem finding. We report a case of sudden cardiac arrest in a 39-year-old male with end-stage renal disease undergoing hemodialysis with a history of Fabry disease by kidney biopsy. Autopsy revealed significant circumferential annular calcification in both mitral and aortic valves with a caseous gross appearance. Histologically, these areas consisted of amorphous basophilic material accompanied by a surrounding granulomatous-appearing infiltrate. Von Kossa staining on non-decalcified tissue revealed strong positive staining, confirming CCMA diagnosis. While identifiable, the atrioventricular node was displaced and distorted by caseous deposits. Toluidine blue staining of myocardium showed osmophilic accumulations, and electron microscopy (EM) showed myeloid/zebra bodies, consistent with Fabry disease. We posit that Fabry disease leads to end-stage kidney disease, altering calcium phosphate metabolism, a proposed mechanism for CCMA. This case highlights the multifactorial nature of sudden cardiac death in decedents with various structural cardiac changes and potential renal-disease-induced electrolyte imbalances. We aim to bring awareness to this rare entity, its potential role in a sudden cardiac death, and to highlight the need to use non-decalcified tissue when staining for calcium to establish the diagnosis.

Pulmonary function trajectories in COVID-19 survivors with and without pre-existing respiratory disease

A significant proportion of COVID-19 survivors still experience a reduced diffusion capacity three and twelve months after discharge. We aimed to compare pulmonary function trajectories between hospitalized COVID-19 patients with pre-existing respiratory disease (PRD) and patients without pre-existing respiratory disease (Non-PRD) at three and twelve months after hospital discharge. This single-centre retrospective cohort study included COVID-19 patients admitted to the VieCuri Medical Centre (Venlo, the Netherlands) between February and December 2020 that were invited to the outpatient clinic at three and twelve months after discharge. During this visit, pulmonary function tests were performed and impairments were based on lower limit of normal. Data of 239 patients were analysed (65% male, 66 ± 10 years, and 26% with a history of respiratory disease). Three months after discharge, 49% and 64% of the Non-PRD patients (n = 177) and PRD patients (n = 62) had a low diffusion capacity, respectively. This improved over time in Non-PRD patients (p = 0.003), but not in PRD patients (p = 0.250). A low diffusion capacity was still observed in 34% and 57% of the Non-PRD and PRD group, respectively, twelve months after discharge. Pulmonary function impairments, mainly a reduced diffusion capacity, are observed among hospitalized COVID-19 patients with PRD and Non-PRD, at three and twelve months follow-up. Although diffusion capacity impairments restore over time in Non-PRD patients, poor recovery was observed among PRD patients.

Finite element analysis of the treatment of a minimally invasive approach combined with a novel anatomical locking plate for scapular body fractures

BackgroundThe minimally invasive approach for the treatment of displaced scapular neck or body fractures has the advantages of less trauma and minimal muscle dissection. In clinical practice, the minimally invasive approach combined with an anatomical locking plate has been used to treat scapular body fractures. In addition, we have made minor modifications to the minimally invasive approach. However, the biomechanical study about the approach combined with an anatomical locking plate in treating scapular body fractures was limited.MethodsFinite element analysis (FEA) was used to conduct the biomechanical comparison between the anatomical locking plate (AP model) and reconstructive plate (RP model) in the treatment of scapular body fractures through the modified minimally invasive approach. A healthy male volunteer with no history of scapula or systemic diseases was recruited. High-resolution computed tomography images of his right scapula were obtained. Two scapula models were constructed and analyzed by the software of Mimics 21.0, Geomagic Wrap 2021, SolidWorks 2021, and ANSYS Workbench 2022, respectively.ResultsThrough static structural analysis, in terms of equivalent von Mises stress, equivalent elastic strain, and total deformation, the AP model exhibited superior safety characteristics, enhanced flexibility, and anticipated stability compared with the RP model. This was evidenced by lower maximum stress, lower maximum strain and displacement.ConclusionThe minimally invasive approach combined with an anatomical locking plate for scapular body fractures had better biomechanical stability. The study provided a biomechanical basis to guide the clinical treatment of scapular body fractures.

Very Late Magmaris Scaffold Restenosis: A 6-year Serial Optical Coherence Tomography Case Report

Abstract Background Bioresorbable scaffolds (BRS) have been proposed as an alternative to drug-eluting stents (DES), offering radial support during the early phases of healing, while potentially reducing the risk of long-term complications. A magnesium-based BRS (MgBRS) have shown promising results after implantation. However, there is a lack of knowledge regarding the long-term outcomes. Case summary A 62-year old man with hypertension, dyslipidemia, family history of ischemic heart disease, and previous myocardial infarction, presented with Non ST-elevation myocardial infarction (NSTEMI). Six years prior he also had a NSTEMI and a mid left anterior descending artery (LAD) lesion was treated with a 3.0/25mm MgBRS. Post-implantation optical coherence tomography (OCT) revealed proximal edge dissection, and a second MgBRS 3.0/15mm was implanted. OCT of the scaffold-treated segment was performed after 6 and 12 months with no sign of restenosis. The current angiogram showed a restenosis in the previously MgBRS treated segment in LAD. OCT showed a plaque rupture in a thin cap fibro-atheroma and scaffold remnants. The lesion was pre-dilated and stented with a 3.0/20mm DES and post-dilated with a 3.5mm non-compliant balloon. Discussion Most cases of late scaffold failure showed acquired malapposition, which also can be related to the degrading process, or uncovered struts, none of which were seen in our case at 6 or 12 months. This case represents an insight into the vascular healing and potential mechanisms for failure of the MgBRS, with serial OCT recording at implantation, and after 6 months, 12 months and 6 years.

Risk factors of acute exacerbation and disease progression in young patients with COPD

ObjectiveWe aimed to elucidate the clinical factors associated with acute exacerbation and disease progression in young patients with chronic obstructive pulmonary disease (COPD).MethodsThis retrospective longitudinal observational study included patients with...

Risk factors for breast cancer subtypes by race and ethnicity: A scoping review.

Breast cancer is comprised of distinct molecular subtypes. Studies have reported differences in risk factor associations with breast cancer subtypes, especially by tumor estrogen receptor (ER) status, but their consistency across racial and ethnic populations has not been comprehensively evaluated. We conducted a qualitative, scoping literature review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis, extension for Scoping Reviews to investigate consistencies in associations between 18 breast cancer risk factors (reproductive, anthropometric, lifestyle, and medical history) and risk of ER-defined subtypes in women who self-identify as Asian, Black or African American, Hispanic or Latina, or White. We reviewed publications between January 1, 1990 and July 1, 2022. Etiologic heterogeneity evidence (convincing, suggestive, none, or inconclusive) was determined by expert consensus. Publications per risk factor ranged from 14 (benign breast disease history) to 66 (parity). Publications were most abundant for White women, followed by Asian, Black or African American, and Hispanic or Latina women. Etiologic heterogeneity evidence was strongest for parity, followed by age at first birth, post-menopausal BMI, oral contraceptive use, and estrogen-only and combined menopausal hormone therapy. Evidence was limited for other risk factors. Findings were consistent across racial and ethnic groups, although the strength of evidence varied. The literature supports etiologic heterogeneity by ER for some established risk factors that are consistent across race and ethnicity groups. However, in non-White populations evidence is limited. Larger, more comparable data in diverse populations is needed to better characterize breast cancer etiologic heterogeneity.

Perceived vulnerability related to health in cancer post-treated adolescent in Iran: a content analysis

BackgroundThe prevalence of cancer is increasing, which significantly impacts the health and various aspects of the lives of cancer-post-treated adolescents. Adolescents with cancer have many negative consequences, including increased vulnerability. Therefore, this study aimed to explore the perceived vulnerability of cancer-post-treated adolescents using a deep examination of experiences and perceptions of participants.MethodsThis study was conducted on 18 participants, who were selected based on purposive sampling in 2023 using a qualitative method through a content analysis approach in Iran. A face-to-face and semi-structured individual interview was used to collect data. Inclusion criteria were children aged 11–19 years, with no history of diseases except cancer, at least one year passed since their last treatment and were aware of their disease. Inclusion criteria for other participants were Parents of childhood cancer survivors whose child is under 19 years old. Health care providers that had at least one year of experience working with and caring for pediatric cancer survivors. The research objective, participation principle, and interview recording were explained to the participants before the interview started. The criteria of credibility, dependability, confirmability and transferability were included to support the trustworthiness of data. The data was analyzed using the conventional qualitative content analysis method and MAXQDA10 software was used for data management.ResultsThe participants included 12 cancer-post-treated adolescents, two parents, two nurses, one doctor, and one cancer charity representative. The data analysis identified three categories: “Confusion in early adolescence”, “Psychological turmoil of disease”, and “Physical burden of the disease”. Finally, the latent content was formulated in to a “Perceived vulnerability” overarching theme.ConclusionIdentifying the patient’s perceptions and beliefs is one of the current health problems to improve the quality of life and facilitate the optimal transition from adolescence to adulthood and adult care. Health professionals have an opportunity to address factors that increase survivors’ sense of vulnerability to health problems by correcting knowledge gaps.

Cohort profile: migraine exposures and cardiovascular health in Hong Kong Chinese women (MECH-HK).

Evidence about the associations of migraine features with cardiovascular risk profiles in Chinese population is lacking. The Migraine Exposures and Cardiovascular Health in Hong Kong Chinese Women (MECH-HK) cohort was constructed to investigate longitudinal migraine features and their cardiovascular implications in Hong Kong Chinese women. We enrolled 4221 Hong Kong Chinese women aged 30 years or above from October 2019 to December 2020. Demographics, reproductive information, lifestyle factors, disease history, blood lipids and glucose, anthropometrics and body compositions were measured during baseline and follow-up. Migraine diagnosis followed the International Classification of Headache Disorders-3 criteria. Migraine features were longitudinally tracked using a migraine diary and summarised by a wide range of epidemiological metrics. Cardiovascular health was assessed using the Framingham risk score (FRS). From October 2021 to June 2023, 3455 women completed the first follow-up measurement. The retention rate was 81.9%. The average age at baseline was 54.40 years. The mean blood glucose, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels were 6.44 mmol/L, 65.06 mg/dL and 102.40 mg/dL, respectively. The average FRS was 0.06. Participants had a 10.3% prevalence of migraine or probable migraine. After 1.27 years of follow-up, the median migraine attack frequency was 0.99 attacks/month, with an incidence rate of 2.55 attacks/person-month and a median duration of 7.70 hours/attack. Sleep problems (64.7%) and stress (54.0%) were the top triggers, while prevalent accompanying symptoms were nausea (67.4%), photophobia (39.9%), phonophobia (30.0%) and vomiting (26.2%). Migraine auras included blurred visions (59.6%), flashing lights (41.3%), blind spots (33.0%), pins and needles (6.4%) and halo (1.8%). The follow-up for the cohort will be implemented every 2 years. MECH-HK will provide unique longitudinal data on migraine features in Hong Kong women. The linkage between migraine features and cardiovascular disease risk progression will be identified by a long-term observation.

Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and sarcopenia in individuals with cancer: a cross-sectional study

BackgroundCancer and sarcopenia are both closely related to lipid metabolism, but the relationship between lipid metabolism and patients with cancer and sarcopenia has not been thoroughly studied. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a reliable measure of lipid metabolism. The purpose of this study was to determine the possible relationship between the NHHR and sarcopenia in individuals with cancer.MethodsData from the National Health and Nutrition Examination Survey (NHANES) database for individuals with cancer, with and without sarcopenia was analyzed using weighted multiple regression equations, weighted regression cubic spline (RCS) analysis, and weighted subgroup analysis.ResultsIn total, 1,602 individuals with cancer were included, of whom 17.1% had sarcopenia. In Adjusted Model 2, the occurrence of sarcopenia was found to be significantly associated with a higher NHHR in cancer (95% confidence interval [CI]:1.01–1.39, P = 0.036). Individuals with high a NHHR had a 2.09-fold higher risk of developing sarcopenia in comparison to those with a low NHHR (95% CI:1.12–3.92, P = 0.022). RCS analysis further identified a U-shaped non-linear relationship between females with cancer and the muscle index. Subgroup analysis indicated that sex was a significant stratifying factor, whereas age, race, marital status, smoking and drinking habits, and history of cardiovascular disease, arthritis, hypertension, and diabetes had no significant impact.ConclusionFrom the perspective of lipid metabolism, the NHHR may serve as an indicator for monitoring and preventing the occurrence of sarcopenia in individuals with cancer, particularly for females with cancer who appear to have greater sensitivity.

Thyroid dysfunction in the wake of Omicron: understanding its role in COVID-19 severity and mortality

PurposeSARS-CoV-2 can invade the thyroid gland. This study was to delineate the risk of thyroid dysfunction amidst the prevalence of the Omicron variant, and to investigate the correlation between thyroid function and Coronavirus disease 2019 (COVID-19) outcomes. The study also aimed to ascertain whether thyroid dysfunction persisted during COVID-19 recovery phase.MethodsThis was a retrospective cohort study. COVID-19 patients from the Renmin Hospital of Wuhan University, China during the epidemic of Omicron variants were included, and their thyroid function were analyzed in groups.ResultsA history of thyroid disease was not associated with COVID-19 outcomes. COVID-19 can lead to a bimodal distribution of thyroid dysfunction. The severity of COVID-19 was inversely proportional to the levels of thyroid- stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4), leading to a higher prevalence of thyroid dysfunction. Severe COVID-19 was a risk factor for euthyroid sick syndrome (ESS) (OR=22.5, 95% CI, 12.1 - 45.6). Neutrophil to lymphocyte ratio mediated the association between severe COVID-19 and ESS (mediation effect ratio = 41.3%, p < 0.001). ESS and decreased indicators of thyroid function were associated with COVID-19 mortality, while high levels of FT3 and FT4 exhibited a protective effect against death. This effect was more significant in women (p < 0.05). During the recovery period, hyperthyroidism was quite uncommon, while a small percentage of individuals (7.7%) continued to exhibit hypothyroidism.ConclusionCOVID-19 severity was linked to thyroid dysfunction. Severe COVID-19 increased the risk of ESS, which was associated with COVID-19 mortality. Post-recovery, hyperthyroidism was rare, but some individuals continued to have hypothyroidism.

Factors affecting the nutritional status of toddlers between the ages of 12-59 months in the workplace of UPTD Puskemas Batu Kambing

Nutritional problems in children at this time are still high. Malnutrition will have an impact on the development and growth of children. The purpose of this study is to find out the Factors Related to the Nutritional Status of Toddlers Aged 12 – 59 Months in the Working Area of the UPTD Batu Kambing Health Center in 2023. The type of research used is quantitative with a crosssectional research design. The population is all mothers who have toddlers aged 12-59 months totaling 610 with a sample of 86 people. The sampling technique is purposive sampling. This research has been carried out in March – April 2023 at the UPTD Batu Kambing Health Center. The data used were primary data and secondary data, namely by conducting interviews with respondents, univariate and bivariate data analysis using the Chi-Square test. The results of the study were less than half, namely 21 respondents (24.4%) who experienced malnutrition, 36 respondents (41.9%) who had a low level of knowledge, 28 respondents (32.6%) with poor parenting and 37 respondents (43.0%) who had a history of infectious diseases. The results of the statistical test showed that the relationship between knowledge and nutritional status was obtained with a value of p = 0.005 (p < 0.05), parenting style with nutritional status was obtained with a value of p = 0.003 (p < 0.05) and the relationship between history of infectious diseases and nutritional status was obtained with a value of p = 0.007 (p < 0.05). It can be concluded that there is a relationship between the level of knowledge, parenting, eating and history of infectious diseases with the nutritional status of toddlers aged 12 – 59 months at the UPTD Batu Kambing Health Center in 2023. It is recommended to health workers to provide counseling on nutrition and the provision of PMT to undernourished children and to mothers to increase maternal knowledge about nutrition and improve maternal parenting by learning how to feed children.

Public Fear of Pancreatic Diseases: Causes and Clinical Outcomes at a Single Korean Center.

The public fear of pancreatic diseases including pancreatic cancer (PC) appears to be growing. The aims of this study were to evaluate the causes of fear of pancreatic diseases and assess clinical outcomes of such individuals. This was a retrospective study of 249 individuals who visited the Pancreatobiliary Diseases Center at Ewha Womans University Seoul Hospital due to the fear of pancreatic diseases between January 2019 and August 2021. Those referred from other departments or external medical facilities were excluded. Collected data included demographic details, comorbidities, causes of fear of pancreatic diseases, and the presence of pancreatic lesions in imaging studies. The median age was 55 years (range, 22 to 82 years). One hundred eleven subjects (44.6%) were male. The causes of fear of pancreatic diseases were abdominal pain (n=144, 57.8%), back pain (n=114, 45.8%), body weight change (n=35, 14.1%), family history of pancreatic diseases (n=32, 12.9%), and others (n=39, 15.7%). Within the group with family history of pancreatic diseases, 25 subjects had a first-degree relative with PC. Of the 200 subjects who underwent imaging, there was no evidence of pancreatic diseases in 182 (91.0%). Pancreatic lesions identified were cystic lesions (n=15, 7.5%), non-specific calcification (n=1, 0.5%), lipoma (n=1, 0.5%), and solid tumor (n=1, 0.5%), later diagnosed as unresectable PC. Abdominal pain and back pain were the major causes of fear of pancreatic diseases. The prevalence of PC among those who underwent imaging was 0.5%. Such characteristics should be considered when consulting individuals with fear of pancreatic diseases.

Neutrophilic Myocarditis: Insights from a Forensic Centre’s Retrospective Study

Background: Neutrophilic myocarditis often stems from bacterial or fungal infections, and it is typically detectable through blood cultures or analyses of the primary infection site. However, research specifically addressing the morphological features of acute myocarditis in complex sepsis cases is scarce, with existing studies primarily dating back to the pre-antibiotic era. Methods: This study constitutes a retrospective and descriptive analysis encompassing 22 forensic cases. We collected data from forensic reports emphasising clinical details, disease history, gross observations, and histopathological findings. Results: The results show that using positive-air-pressure ventilation could be related to cardiac inflammation (45.45%, 10/22). Despite large-spectrum antibiotic therapy, the blood samples were positive for Staphylococcus aureus (MRSA strain), Klebsiella pneumoniae (ESBL strain), Acinetobacter baumannii, and Pseudomonas aeruginosa. Colonies developed in the myocardium of 36% of the patients (8/22), where 4 of them had septic emboli. Fungal myocarditis accompanied bacterial infections (2/8) and were unsuspected clinically. Background changes, such as interstitial fibrosis and arteriosclerosis, were associated with a greater degree of inflammation and septic embolism. Conclusion: Neutrophilic myocarditis in patients with emerging sepsis is linked to fatal virulent infections, where bacteria and/or fungi contaminate and impair the myocardium syncytium. Prolonged hospitalisation and positive-air-pressure ventilation may be a risk factor for this condition and needs further research.

Effectiveness of baricitinib in acquired reactive perforating collagenosis: a case report

BackgroundAcquired reactive perforating collagenosis (ARPC) poses a clinical challenge with an unclear pathogenesis. This disease has been frequently proven resistant to immunosuppressive treatments, significantly affecting the quality of life of patients. In this report, we highlight the efficacy of baricitinib as a viable option for maintenance therapy in ARPC.Case summaryAn 81-year-old woman presented to our hospital with recurrent pruritus and cup-like ulcerated lesions on her trunk and limbs persisting for 1 year. She exhibited limited response to oral antihistamines and topical steroids. Past medical history revealed a prolonged history of coronary heart disease and type 2 diabetes spanning several years to decades. Histopathological examination revealed cup-shaped depressions filled with necrotic inflammatory debris. In the dermis, a mixed inflammatory infiltrate composed of lymphocytes and histiocytes was observed. Van Gieson staining indicated the elimination of fibrous tissue extending from the dermis into the epidermis. Consequently, a diagnosis of ARPC was established. Due to the inadequate response to conventional treatments and the severe itching, we initiated baricitinib therapy for ARPC, resulting in gradual symptom improvement. Follow-up assessments showed no adverse reactions and normal laboratory findings.ConclusionThe case report suggests that baricitinib might offer significant therapeutic benefits for ARPC.

Features of the course of the new coronavirus infection COVID-19 in patients with chronic kidney disease

BACKGROUND: CKD is one of the main comorbidities in those who die from COVID-19. Renal injury is the most common nonpulmonary infection of SARS-CoV-2 and has a wide range of manifestations, ranging from mild proteinuria and hematuria to progressive acute kidney injury (AKI) requiring renal replacement therapy (RRT).THE AIM: to study the features of the course of the new coronavirus infection COVID-19 in patients with chronic kidney disease.PATIENTS AND METHODS: The study included 79 patients with confirmed new coronavirus infection COVID-19 who hospitalized. The first group consisted of people with a history of CKD (44 people), the second group included people without a history of CKD (35 people). The diagnosis of CKD established based on the calculation of glomerular filtration rate using the CKD-EPI formula. The comorbidity index calculated using two scales: Charlson and CIRS-G. Statistical data analysis carried out using the Statistica 12.0 application package (StatSoft Inc., USA).RESULTS: Patients with COVID-19 and CKD had a higher comorbidity index: according to the Charlson index in one group of patients the indicator was 7 [5.0-9.0], and in group 2 it was 5 [4.0-6.0] (p<0.001). According to the CIRS-G index, in one group the indicator was 9 [7-11.5], in two group it was 4 [2-6] (p <0.001). Patients in one group had a greater degree of damage to the lung tissue according to MSCT of the OGK; in laboratory tests, the levels of CRP, ferritin, LDH, and d-dimer were higher; leukocytosis with a neutrophil shift in the leukocyte count observed.CONCLUSION: Patients with a history of chronic kidney disease (CKD) had more severe COVID-19 and higher mortality.

Causal association between telomere length and female reproductive endocrine diseases: a univariable and multivariable Mendelian randomization analysis

BackgroundThe relationship between leukocyte telomere length (LTL) and female reproductive endocrine diseases has gained significant attention and research interest in recent years. However, there is still limited understanding of the exact impacts of LTL on these diseases. Therefore, the primary objective of this study was to investigate the genetic causal association between LTL and female reproductive endocrine diseases by employing Mendelian randomization (MR) analysis.MethodsInstruments for assessing genetic variation associated with exposure and outcome were derived from summary data of published genome-wide association studies (GWAS). Inverse-variance weighted (IVW) was utilized as the main analysis method to investigate the causal relationship between LTL and female reproductive endocrine diseases. The exposure data were obtained from the UK Biobanks GWAS dataset, comprising 472,174 participants of European ancestry. The outcome data were acquired from the FinnGen consortium, including abnormal uterine bleeding (menorrhagia and oligomenorrhea), endometriosis (ovarian endometrioma and adenomyosis), infertility, polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI) and premenstrual syndrome (PMS). Furthermore, to account for potential confounding factors such as smoking, alcohol consumption, insomnia, body mass index (BMI) and a history of pelvic inflammatory disease (PID), multivariable MR (MVMR) analysis was also conducted. Lastly, a series of pleiotropy tests and sensitivity analyses were performed to ensure the reliability and robustness of our findings. P < 0.0063 was considered to indicate statistically significant causality following Bonferroni correction.ResultsOur univariable MR analysis demonstrated that longer LTL was causally associated with an increased risk of menorrhagia (IVW: odds ratio [OR]: 1.1803; 95% confidence interval [CI]: 1.0880–1.2804; P = 0.0001) and ovarian endometrioma (IVW: OR: 1.2946; 95%CI: 1.0970–1.5278; P = 0.0022) at the Bonferroni significance level. However, no significant correlation was observed between LTL and oligomenorrhea (IVW: OR: 1.0124; 95%CI: 0.7350–1.3946; P = 0.9398), adenomyosis (IVW: OR: 1.1978; 95%CI: 0.9983–1.4372; P = 0.0522), infertility (IVW: OR: 1.0735; 95%CI: 0.9671–1.1915; P = 0.1828), PCOS (IVW: OR: 1.0633; 95%CI: 0.7919–1.4278; P = 0.6829), POI (IVW: OR: 0.8971; 95%CI: 0.5644–1.4257; P = 0.6459) or PMS (IVW: OR: 0.7749; 95%CI: 0.4137–1.4513; P = 0.4256). Reverse MR analysis indicated that female reproductive endocrine diseases have no causal effect on LTL. MVMR analysis suggested that the causal effect of LTL on menorrhagia and ovarian endometrioma remained significant after accounting for smoking, alcohol consumption, insomnia, BMI and a history of PID. Pleiotropic and sensitivity analyses also showed robustness of our results.ConclusionThe results of our bidirectional two-sample MR analysis revealed that genetically predicted longer LTL significantly increased the risk of menorrhagia and ovarian endometrioma, which is consistent with the findings from MVMR studies. However, we did not notice any significant effects of LTL on oligomenorrhea, adenomyosis, infertility, PCOS, POI or PMS. Additionally, reproductive endocrine disorders were found to have no impact on LTL. To enhance our understanding of the effect and underlying mechanism of LTL on female reproductive endocrine diseases, further large-scale studies are warranted in the future.

Development and validation of 10-year risk prediction models of cardiovascular disease in Chinese type 2 diabetes mellitus patients in primary care using interpretable machine learning-based methods.

To develop 10-year cardiovascular disease (CVD) risk prediction models in Chinese patients with type 2 diabetes mellitus (T2DM) managed in primary care using machine learning (ML) methods. In this 10-year population-based retrospective cohort study, 141 516 Chinese T2DM patients aged 18 years or above, without history of CVD or end-stage renal disease and managed in public primary care clinics in 2008, were included and followed up until December 2017. Two-thirds of the patients were randomly selected to develop sex-specific CVD risk prediction models. The remaining one-third of patients were used as the validation sample to evaluate the discrimination and calibration of the models. ML-based methods were applied to missing data imputation, predictor selection, risk prediction modelling, model interpretation, and model evaluation. Cox regression was used to develop the statistical models in parallel for comparison. During a median follow-up of 9.75 years, 32 445 patients (22.9%) developed CVD. Age, T2DM duration, urine albumin-to-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), systolic blood pressure variability and glycated haemoglobin (HbA1c) variability were the most important predictors. ML models also identified nonlinear effects of several predictors, particularly the U-shaped effects of eGFR and body mass index. The ML models showed a Harrell's C statistic of >0.80 and good calibration. The ML models performed significantly better than the Cox regression models in CVD risk prediction and achieved better risk stratification for individual patients. Using routinely available predictors and ML-based algorithms, this study established 10-year CVD risk prediction models for Chinese T2DM patients in primary care. The findings highlight the importance of renal function indicators, and variability in both blood pressure and HbA1c as CVD predictors, which deserve more clinical attention. The derived risk prediction tools have the potential to support clinical decision making and encourage patients towards self-care, subject to further research confirming the models' feasibility, acceptability and applicability at the point of care.

Diagnostic Scale for Acute Appendicitis to Prevent General Peritonitis in Children

This article presents the development and implementation of a diagnostic scale for acute appendicitis in children over 5 years of age with the aim of effectively preventing general peritonitis in children. The study is based on an extensive analysis of clinical cases and medical observation data. The proposed diagnostic scale, based on a comprehensive analysis of the disease history, clinical signs, and laboratory parameters, demonstrates high accuracy and reliability in determining acute appendicitis in children, which contributes to the timely initiation of treatment and reducing the risk of developing intra-abdominal complications including generalized peritonitis.

Cutaneous Involvement by Refractory Celiac Disease Type 2 Histologically Mimicking Mycosis Fungoides.

Refractory celiac disease (RCD) is a rare condition characterized by persistent malabsorptive symptoms and villous atrophy despite a gluten-free diet. While RCD type 1 has a normal intraepithelial lymphocyte phenotype, RCD type 2 is defined by the presence of immunophenotypically aberrant and monoclonal intraepithelial T lymphocytes, with a high propensity to transform to enteropathy-associated T-cell lymphoma (EATL). Although dermatological manifestations of celiac disease are common, presentation with cutaneous involvement by abnormal lymphocytes of RCD type 2 or EATL is rare, with few histologic descriptions in the literature. We describe the case of a 66-year-old man with a history of celiac disease presenting with a generalized, erythematous papular rash over his torso, upper arms, and legs. Biopsy of his skin lesions showed prominent hyperkeratosis with underlying spongiosis and interface change. Increased intraepithelial (epidermotropic) lymphocytes were observed, out of proportion to the level of spongiosis, but not overly atypical in appearance. Immunohistochemistry revealed an aberrant T-cell immunophenotype (CD3/2/7 positive; CD5/4/8 negative), raising suspicion for a cutaneous T-cell lymphoproliferative disorder. A duodenal biopsy demonstrated total villous atrophy with a morphologically bland population of epitheliotropic T lymphocytes showing the same aberrant immunophenotype. Similar cells were also identified by flow cytometry in the peripheral blood. In conjunction with the history of celiac disease, a diagnosis of RCD type 2 or 'EATL in situ' with cutaneous involvement was made. Cutaneous RCD type 2 or EATL should be considered as differential diagnoses in patients with a history of celiac disease and histopathology reminiscent of epidermotropic forms of cutaneous T-cell lymphoma.

Significance of family history of cholelithiasis in a Pakistani population: A single center, descriptive cross-sectional study.

Linkage studies have indicated a potential genetic predisposition to cholelithiasis. This study aims to determine the frequency of positive family history of gallstone disease in patients presenting with gallstones in a Pakistani population. A descriptive, cross-sectional study was conducted at the surgical department of the University of Lahore Teaching Hospital from June 30, 2023 to August 30, 2023. A total of 102 radiologically confirmed cholelithiasis patients were enrolled. Out of 102 participants, 75.5% (n = 77) were females, with a mean age at presentation of 42.1 ± 12.1 years. The study found that 32.4% (n = 33) of participants had a single family member with gallstones, 3.9% (n = 4) had 2 family members affected, and 1% (n = 1) had 3 family members affected. The attributable risk of genetics from our study was 37.2%. Additionally, there was no significant association between positive family history and earlier onset of disease. A significant percentage of Pakistani population may have gallstone disease due to genetic factors.