High-risk Group Research Articles

Hepatocellular Cancer Surveillance in Patients with Advanced Chronic Liver Disease

BackgroundPatients with advanced chronic liver disease (ACLD) are at high risk of developing hepatocellular carcinoma (HCC). Therefore, biannual surveillance is recommended. This large-scale multicenter study aimed to stratify the risk of HCC development in ACLD.MethodsFrom 3016 patients with ACLD screened in 17 European and Chinese centers, 2340 patients with liver stiffness measurement (LSM) determined using different techniques (two-dimensional shear-wave elastography [2D-SWE], transient elastography, and point shear-wave elastography) and with different disease severities were included. Cox regression was used to explore risk factors for HCC. We used these data to create an algorithm, named PLEASE, but referred to in this manuscript as “the algorithm”; the algorithm was validated in internal and two external cohorts across elastography techniques.ResultsHCC developed in 127 (5.4%) patients during follow-up. LSM by 2D-SWE (hazard ratio: 2.28) was found to be associated with developing HCC, alongside age, sex, etiology, and platelet count (C-index: 0.8428). We thus established the algorithm with applicable cutoffs, assigning a maximum of six points: platelet count less than 150×109/l, LSM greater than or equal to 15 kPa, age greater than or equal to 50 years, male sex, controlled/uncontrolled viral hepatitis, or presence of steatotic liver diseases. Within 2 years, with a median follow-up of 13.7 months, patients in the high-risk group (≥4 points) had an HCC incidence of 15.6% (95% confidence interval [CI], 12.1% to 18.7%) compared with the low-risk group, at 1.7% (95% CI, 0.9% to 2.5%).ConclusionsOur algorithm stratified patients into two groups: those at higher risk of developing HCC and those at lower risk. Our data provide equipoise to test the prospective utility of the algorithm with respect to clinical decisions about screening patients with ACLD for incident HCC. (Funded by the German Research Foundation and others; ClinicalTrials.gov number, NCT03389152.)

The Universal Vital Assessment (UVA) score at 6 hours post-resuscitation predicts mortality in hospitalized adults with severe sepsis in Mbarara, Uganda.

Sepsis is the leading cause of global death with the highest burden found in sub-Saharan Africa (sSA). The Universal Vital Assessment (UVA) score is a validated resource-appropriate clinical tool to identify hospitalized patients in sSA who are at risk of in-hospital mortality. Whether a decrease in the UVA score over 6 hours of resuscitation from sepsis is associated with improved outcomes is unknown. We aimed to determine (1) the association between 6-hour UVA score and in-hospital mortality, and (2) if a decrease in UVA score from admission to 6 hours was associated with improved in-hospital mortality. We analyzed data from participants with severe sepsis aged ≥14 years enrolled at the Mbarara Regional Referral Hospital in Uganda from October 2014 through May 2015. Among 197 participants, the median (interquartile range) age was 34 (27-47) years, 99 (50%) were female and 116 (59%) were living with HIV. At 6 hours, of the 65 participants in the high-risk group, 28 (43%) died compared to 28 (30%) of 94 in the medium-risk group (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.29,1.08, p = 0.086) and 3 (9%) of 33 in the low-risk group (OR 0.13, 95% CI 0.03, 0.42, p = 0.002). In a univariate analysis of the 85 participants who improved their UVA risk group at 6 hours, 20 (23%) died compared to 39 (36%) of 107 participants who did not improve (OR 0.54, 95% CI 0.27-1.06, p = 0.055). In the multivariable analysis, the UVA score at 6 hours (adjusted OR [aOR] 1.26, 95%CI 1.10-1.45, p<0.001) was associated with in-hospital mortality. When adjusted for age and sex, improvement in the UVA risk group over 6 hours was associated with a non-statistically significant 43% decrease in odds of mortality (aOR 0.57, 95%CI 0.29-1.07, p = 0.08). Targeting a decrease in UVA score over 6 hours from admission may be a useful clinical endpoint for sepsis resuscitation in sSA, but this would need to be proven in a clinical trial.

Clinical reality and challenges with familial hypercholesterolemia patients' management. 2024 results from the Regional Center for Rare Diseases (RCRD) Registry in Poland

BackgroundDespite advancements in early diagnosis and effective medications in last decade, most heterozygous familial hypercholesterolemia (heFH) patients still fail to achieve their low-density lipoprotein cholesterol (LDL-C) goals and remain at residual cardiovascular disease risk. We present recent data from the regional FH registry in Poland, highlighting the challenges and real-life clinical management of FH patients. MethodsThe registry is held at the Regional Centre for Rare Diseases, founded in 2016, at the 2nd largest, supraregional hospital in Poland, where >80 different rare diseases in patients from all over Poland are diagnosed and treated, including phenotypically or genetically diagnosed FH patients. Our analysis focused on both children and adult FH patients, excluding those treated with inclisiran due to a small sample size (n = 5). ResultsWe studied 173 consecutive heFH patients, median age for adult population was 40 years (range: 27–57), of whom 56.14 % were women. Among the population, 82.1 % were adults (n = 142), and 31 were children (17.92 %; median age 9 (8–13), females 58.16 %). Children exhibited lower total cholesterol and triglyceride levels compared to adults, with no significant differences in LDL-C and high-density lipoprotein cholesterol (HDL-C) levels. Molecular diagnosis in the whole population revealed that 76.6 % had an LDL receptor (LDLR) mutation, while 23.4 % had an apolipoprotein B (APOB) mutation. Risk assessment categorized patients into high (70.7 %), very high (22.1 %), and extremely high (7.1 %) risk groups. Triple therapy achieved treatment goals in 61.76 % of adults and 70.97 % of children. At baseline, 36.62 % of adult patients were not using statins. High-intensity statin therapy combined with ezetimibe was initiated for the remaining patients. Only 3.33 % of patients avoided statins due to complete intolerance. Ezetimibe was used in 57.27 % of patients (mostly in combination therapy), and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were prescribed for 28.17 % FH patients. In adults receiving statin and ezetimibe therapy, median achieved LDL-C was 141 mg/dl (107–184). For triple therapy, median achieved LDL-C was 52.5 mg/dL (32–86.5). Overall median achieved LDL-C in the study population was 99.5 mg/dl (57.5–145.4). PCSK9 inhibitors reduced LDL-C by 165.6 mg/dl. Combination therapy did not significantly alter baseline lipoprotein(a) (Lp(a)) levels (p = 0.134), and PCSK9 inhibitors led to a mean Lp(a) reduction of 18.66 mg/dl (45 % reduction; p = 0.013). Multivariable regression analysis identified key factors for achieving LDL-C targets in FH patients: DLCN total score, DLCN category, ezetimibe use, and PCSK9 inhibitors. ConclusionsIn Poland, FH patients are often diagnosed too late (usually over 40 years of age), and many still do not reach their LDL-C goals. Combination LLT double or triple therapy significantly increases the likelihood of achieving LDL-C targets – even up to fivefold. Therefore, unrestricted access to PCSK9 inhibitors for all FH patients is crucial, without the current limitations imposed by drug reimbursement programs like B101.

Hepatocellular Carcinoma in Acute Hepatic Porphyria: A Meta-Analysis of Observational Studies.

Hepatocellular carcinoma (HCC) is a long-term complication of acute hepatic porphyria (AHP) inclusive of acute intermittent porphyria [AIP], variegate porphyria [VP], or hereditary coproporphyria [HCP]. Data on HCC risk in AHP patients are limited and heterogeneous. We performed this meta-analysis with aims to (a) determine incidence of HCC in AHP and specific subtypes of AHP and (b) examine high-risk groups for HCC. Data from studies reporting HCC development in AHP patients were pooled and reported per 100 person years with 95% confidence intervals (CI). 12 observational (5 prospective) studies (11 Europe and 1 US) on 2735 patients (mean age 54.8 yrs., 62% females) with AHP (80% AIP) were analyzed. 115 HCC cases were observed with HCC incidence per 100 person years of 0.3 (0.2-0.5) in AHP, 0.4 (0.2-0.6) in AIP, 0.3 (0-0.4) in VP, and 0.2 (0.1-0.6) in HCP. The risk was 0.4 (0.2-0.6) in females, 0.3 (0.1-0.5) in males, 0.9 (0.1-1.7) in symptomatic, and 0.5 (0-1.6) in asymptomatic patients. Analyses were heterogeneous with publication bias. AHP patients with HCC were older females with a higher prevalence of cirrhosis, alcohol use, and viral hepatitis. The annual incidence of HCC in AHP patients is 0.3%, with higher risk in AIP, older females, symptomatic patients, and those with other risk factors of liver disease. Future studies pooling individual patient data and overcoming limitations of the current meta-analysis are needed as a basis for deriving a effective screening and surveillance approach for HCC in patients with AHP.

Prognostic prediction and treatment options for gastric signet ring cell carcinoma: a SEER database analysis.

In recent years, the overall incidence of gastric cancer has decreased. However, the incidence of gastric signet ring cell carcinoma (SRCC) is still increasing year by year. Compared with other subtypes (non-SRCC) such as adenocarcinoma, SRCC usually exhibits a more aggressive biological behavior. Therefore, studying the prognostic differences and factors associated with SRCC is essential to improve the accuracy of diagnosis and prognosis. The purpose of this study was to investigate the prognostic factors influencing the prognosis of patients with SRCC and to develop personalized treatments for different subgroups of patients. The data on gastric SRCC patients and gastric adenocarcinoma (AC) patients from 1992 to 2020 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The data of gastric SRCC as the external validation group was reviewed from the First Affiliated Hospital of Soochow University. The overall survival (OS) and cancer specific survival (CSS) at 1 and 2 years were predicted for SRCC patients by constructing prognostic nomograms. A series of validation methods, including Akaike information criterion (AIC), decision curve analysis (DCA), calibration curve analysis, the concordance index (C-index) and the area under the receiver operating characteristic (AUC) curve, were used to verify the accuracy and reliability of the models. In all, 549 patients with SRCC were included after propensity score matching (PSM). Multivariate Cox regression analysis showed that T stage, N stage, M stage and surgical approach were independent risk factors affecting the prognosis of SRCC patients. A prognostic nomogram was constructed and validated as an accurate model for SRCC patients after scoring by receiver operating characteristic curve (ROC) curves and calibration plots. The patients were further divided into high-risk and low-risk groups, and the Kaplan-Meier curves showed that SRCC patients in the low-risk group could receive only surgery without chemotherapy, while chemotherapy plus surgery was a better option for SRCC patients in the high-risk group. The prognosis for SRCC was less favorable than that of AC in terms of CSS. The nomograms were developed and validated to predict OS and CSS in patients with SRCC, helping in developing appropriate individualized treatment schedules.

Coagulation-related genes for thyroid cancer prognosis, immune infltration, staging, and drug sensitivity.

Thyroid cancer (THCA) is the most common endocrine tumor. Coagulation may be associated with the development of cancer, but its role in THCA patients is not yet clear. In this study, we determined the predictive value of coagulation biomarker D-dimer for THCA patient lateral lymph node metastasis (LLNM) through receiver operating characteristics (ROC) analysis and logistic regression analysis. Subsequently, this study used the TCGA database to identify coagulation-related molecular subtypes through consensus clustering analysis and compared their prognosis. We identified coagulation-related genes (CRGs) associated with prognosis in thyroid cancer through gene expression data and clinical information, and constructed a prognostic model by selecting the prognostic CRGs using LASSO regression. Patients were divided into high-risk and low-risk groups based on the median score. Subsequently, prognosis, clinical characteristics, gene mutation occurrence, immune infiltration, function, and drug sensitivity of the two groups were analyzed. We also constructed a nomogram combining the model and clinical features. Finally, the expression of the prognostic CRGs was validated by RT-qPCR. D-dimers had better performance in predicting LLNM(the area under the curve was 0.656 (95% CI 0.580-0.733), with a cut-off value of 0.065 mg/l), and D-dimer>0.065mg/l was an independent predictor of LLNM. Then, we selected 8 prognostic CRGs to construct a predictive model. The prognosis of low-risk group patients was significantly better than that of high-risk group (P<0.001). The results showed significant differences in clinical characteristics, gene mutation occurrence, immune infiltration, function, and drug sensitivity between the high-risk and low-risk groups. We validated by qPCR that these 8 prognostic CRGs were overexpressed in THCA cell lines. Overall, this study provided an in-depth exploration of the potential role of the coagulation in thyroid cancer and its clinical significance, offering a new theoretical basis and research direction for personalized therapy and prognostic evaluation.

Clinical study of immune-targeting combined with attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma

Objective: To evaluate the efficacy and safety of brentuximab vedotin (BV) combined with rituximab and attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma (cHL). Methods: A prospective, non-randomized, risk-assigned study. Clinical data (including age, gender, B symptoms, bulky disease, CD30 and Epstein-Barr virus-encoded RNA(EBER) expression, clinical stage, risk stratification, etc.) of 28 intermediate to high-risk cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2022 to May 2024 were collected. Immuno-targeted combined with attenuated chemotherapy was administered based on risk stratification and early treatment response. The patients were followed up until May 1st, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 28 patients, there were 22 males and 6 females, the age was 12 (5,16) years, 16 cases (57%) presented with bulky disease and 10 cases (36%) with B symptoms. The most common pathological type was nodular sclerosis (14 cases, 50%). There were 7 cases of stage Ⅱ, 14 cases of stage Ⅲ and 7 cases of stage Ⅳ according to the Ann Arbor staging system. There were 5 cases in the intermediate-risk group and 23 cases in the high-risk group. EBER was positive in 20 cases (71%) and negative in 6 cases (21%), and CD30 antigen was expressed in tumor cells of all enrolled children. Treatment duration: 5 cases (18%) received 4 courses of treatment, 21 cases (75%) received 6 courses of treatment, and 2 cases (7%) received 8 courses of treatment, 25 cases (89%) achieved complete metabolism response (CMR) through early assessment after 2 courses of chemotherapy. The CMR rates were 100% in intermediate-risk group and 87% in high-risk group, respectively. Four patients (14%) finally received residual field radiotherapy. Toxicities included grade Ⅰ-Ⅱ myelosuppression, early infusion reaction and mild peripheral neuropathy, only one case of grade 3 adverse events was recorded and did not affect sequential treatment. At the end of treatment and 3 months of follow-up, the levels of IgA, IgG and IgM were all decreased compared with the baseline before chemotherapy, and the total B cell count began to be lower than the level before chemotherapy at the early stage of treatment (after 2 courses). The total B cell count monitored during treatment was 50 (0, 101)×106/L and was 12 (0, 25)×106/L at the end of treatment. The follow-up time was 6 (3, 13) months, all 28 children had event-free survival and all achieved complete remission. At 6 and 9 months of follow-up, IgA, IgG, IgM and total B cell counts returned to pre-chemotherapy baseline levels, respectively. Conclusion: BV combined with rituximab attenuated chemotherapy has demonstrated efficacy and a tolerable safety profile in the treatment of cHL in children, and significantly reduce radiation rate.

Incidence, characteristics, and outcome of noncardiac surgery following transcatheter aortic valve implantation.

Planning noncardiac surgery after transcatheter aortic valve implantation (TAVI) is challenging. We evaluated the incidence, characteristics, and outcome of noncardiac surgeries in patients who underwent TAVI. We retrieved data from the Prospective Segeberg TAVI registry of all patients who received TAVI between 2007 and 2020. Type, timing, urgency, and risk of noncardiac surgery were assessed. We evaluated the patients' clinical outcomes within 30days following noncardiac surgery that included death, myocardial infarction, bleeding, stroke, and acute heart failure. A composite outcome of all adverse events was proposed to independently predict 30day adverse events. Among 1602 patients, 104 patients (mean age, 79.9 ± 7.14 years; 61 (58.7%) females) underwent 148 noncardiac surgeries after TAVI. More than half of the noncardiac surgeries were considered elective (n = 84, 56.7%). Procedures were categorized into low-risk (n = 27, 18.2%), intermediate-risk (n = 102, 68.9%), and high-risk (n = 19, 12.8%) surgery. The composite outcome of adverse events occurred after 57 noncardiac surgeries (38.5% of all procedures) and after more than half of the surgeries in the high-risk group (n = 11, 57.9%). Major or life-threatening bleeding occurred in 24 noncardiac surgeries (19.1%) and was more frequent in high-risk surgeries than in low- and intermediate-risk surgeries (36.8%, p < 0.047). High-risk category of surgery was independently associated with increased risk of the composite outcome (adjusted OR, 3.99; 95% CI 1.12-14.23; p = 0.033). Noncardiac surgery after TAVI was performed in 6.5% patient of our study cohort. High-risk noncardiac surgeries were associated with increased risk of adverse events.

Candidemia in Pediatric-Clinic: Frequency of Occurrence, Candida Species, Antifungal Susceptibilities, and Effects on Mortality (2020-2024).

Objective: Invasive candidiasis is defined as an important infection that increases the duration of patients' hospital stay, costs, mortality and morbidity. In this study, we aimed to investigate the frequency of candidiasis in blood cultures of pediatric hematology patients, Candida species, antifungal susceptibilities, and their effects on mortality. Materials and Methods: Patients with Candida growth in their blood cultures at follow-up in the pediatric hematology clinic of our hospital between 2020 and 2024 were included in the study. Age, gender, primary diseases and risk levels, subtypes and antifungal susceptibilities of Candida grown in blood cultures, the presence of neutropenia in patients, the antifungals used for prophylaxis and treatment, the duration of infection, other bacteria grown additionally during the fungal infection period, the local infection source and the patients' discharge status were obtained from medical records. These constituted the study data. Results: Blood cultures were requested for 594 patients from the Pediatric hematology Clinic, and Candida was grown in only 37 (6.7%) of them. A total of 43.2% of them were the Candida parapsilosis complex, 29.7% were Candida albicans and 8.1% were the Candida haemulonii complex. Antifungal susceptibilities were over 90% for anidulafungin, micafungin, caspofungin, posaconazole, itraconazole and amphotericin B, followed by 86.7% for fluconazole and 84.4% for voriconazole. The mean age of the patient group was 6.8 years, 50.5% of whom were female and 40.5% of whom were male. The Candida infections developed on the 12.1th day of the neutropenia process on average. The mean invasive Candida infection period was 7 days. A total of 18.9% had a second bacterial infection and 13.5% had a local infection. A total of 51.4% had a single antifungal, 18.9% had two antifungals and 2.1% had more than two antifungals. A total of 35.1% of the patients with invasive candidiasis died. The primary diagnosis of the disease, Patient risk level, and the female gender were important factors affetting mortality. Conclusions: In a pediatric hematology clinic, the non-albicans group in invasive candidiasis infections was notable, with the C. parapsilosis complex occurring most frequently. There was still a high sensitivity to echinocandin antifungals and a decreased sensitivity to triazoles. It was found that the factor of the clinical diagnosis, being in the high-risk group and being female had significant effects on the survival rate of patients with candidiasis infections.

Identification of a pyroptosis-related long noncoding RNA signature for determining the prognosis and immune status of hepatocellular carcinoma patients.

Despite improvements in cancer screening and diagnosis, hepatocellular carcinoma (HCC) is still diagnosed at an advanced stage, and the prognosis is worse than that of early HCC patients. Therefore, better molecular markers and therapeutic targets in HCC are required. We investigated the predictive value of pyroptosis-related long noncoding RNAs (lncRNAs) in HCC and the effects of these lncRNAs on the immune microenvironment of HCC. RNA sequencing data of HCC patients were extracted from The Cancer Genome Atlas (TCGA) database to identify differentially expressed pyroptosis-related lncRNAs related to overall survival (OS). A model was established to verify the character of pyroptosis-associated lncRNAs in the tumor microenvironment, and their prognostic value was evaluated. A total of 721 PR lncRNAs were identified based on the analysis of the TCGA database. Univariate Cox analysis revealed 37 survival-related PRlncRNAs with prognostic values. As a result of least absolute shrinkage and selection operator (LASSO) regression analysis, 'ELFN-AS1', AC099850.3, AC073389.3, 'HPN-AS1', AC009283.1, and AL139289.1 showed prognostic value. Kaplan-Meier analysis indicated that the OS of the high-risk set was worse than those of the low-risk set in both the training and testing cohorts. Univariate and multivariate analyses revealed that the risk score was a better independent prognostic factor than the stage. The precision of the lncRNA signature was confirmed using receiver operating characteristic curve (ROC) analysis. Immuneand metabolism-related pathways were enriched in both the lowand high-risk groups. Gene set enrichment analysis suggested that the identified lncRNAs regulate HCC tumorigenesis and prognosis by modulating metabolism. Various algorithms were used to confirm the significant differences in immune cells between these 2 groups. These findings could contribute to the development and validation of favorable biomarkers, improve the prognosis and survival of HCC, and help in developed individualized treatment plans for HCC.

U-shaped association between dietary niacin intake and chronic kidney disease among US elderly: a nationwide cross-sectional study.

In addition to hypertension or diabetes, elderly people are also considered one of the high-risk groups for chronic kidney disease (CKD). Although niacin is recognized for its renal protective properties, the link between dietary niacin intake and CKD remains uncertain. This study investigated this relationship in the elderly. We included participants aged 60 and older from the National Health and Nutrition Examination Survey (NHANES) for the years 2003-2018. Dietary niacin intake was assessed through two non-consecutive 24-hour dietary recalls. CKD was diagnosed in individuals with a urine albumin-to-creatinine ratio exceeding 30 mg/g or an estimated glomerular filtration rate below 60 mL/min per 1.73 m^2. The study cohort comprised 4,649 participants, 1,632 of whom had CKD. Propensity score matching (PSM) was utilized to adjust for baseline differences between the groups. Our analysis, using smooth curve fitting and generalized additive models both before and after PSM, found a U-shaped curve depicting the relationship between dietary niacin intake and CKD risk, confirmed by a log-likelihood ratio test (P < 0.05). Threshold effect analysis (after PSM) indicated a reduced risk of CKD in older adults with a niacin intake below 38.83 mg per day [odds ratio (OR)= 0.99, 95% confidence interval (CI) 0.97-1.00]. In contrast, higher intake levels significantly increased the risk (OR = 1.03, 95% CI 1.00-1.06). Subgroup analysis indicated that these associations were consistent across different stratification variables (P for interaction > 0.05). Our findings suggested a U-shaped association between dietary niacin intake and CKD risk among older Americans. However, further prospective cohort studies are needed to confirm this finding.

Serial Multiple Mediation of the Marital Satisfaction and Parenting Competence in the Relationship Between Postpartum Depression and Parent-Infant Attachment in First-Time Parents With Low- and High-Risk Pregnancy Experiences: A Cross-Sectional Study.

Little is known regarding the effects of postpartum depression on parent-infant attachment in high-risk parents. Based on Mercer's theory of becoming a mother, this study aimed to (1) examine the mediating effects of marital satisfaction and parenting competence in the relationship between postpartum depression and parent-infant attachment using a serial mediation model in first-time parent couples during the first 6 months postpartum, and (2) compare the serial mediation models between parents who had experienced low-risk and high-risk pregnancies. In this cross-sectional study, a total of 194 first-time parent couples at 1 to 6 months postpartum were included. Participants completed an online survey on postpartum depression, marital satisfaction, parenting competence, and parent-infant attachment. In both low- and high-risk groups, parenting competence was a common mediator of the impact of postpartum depression on parent-infant attachment. A sequential mediation effect involving both marital satisfaction and parenting competence was observed in high-risk mothers. Our findings suggest that the adverse impacts of postpartum depression on parent-infant attachment can be mitigated by boosting parenting competence or improving the marital satisfaction in couples experiencing first high-risk pregnancy.

Exploratory Data Analyses Indicate an Overuse of Dietary Supplements among Male Gym Users in Germany

Background: Dietary supplements (DS) are very popular with the general population, physically active people and professional athletes are often taken without professional advice. Adverse effects on consumer health are increasingly being reported and there are concerns about overdoses of certain nutrients. There are initial indications that some groups of people have a higher affinity to DS than others. It appears that the type of sport and possibly gym membership could have an influence on consumer behaviour. Therefore, this study aimed to identify high consumer groups of DS among the general population in Germany. Methods: The consumption of DS was assessed using an online questionnaire including information about physical activity, gym membership and the consumption and intake doses of DS. Completed questionnaires were returned by 244 participants (m=153, f=91; 30.7±10.4 years SD). The answer options were valued, and subjects were categorized in low, average and high consumers (indicating overdosing). A configural frequency analysis was performed using the independent variables gender, gym membership, consumption. The configurations were tested with an exact binomial test and the p-value was corrected according to Bonferroni (0.05/12=0.0042). Results: Three significant configurations were found (p≤0.0042). The configuration, ‘male-gym member-average consumption’ as well as ‘male-gym member-high consumption’ were significantly overrepresented. Male gym members with low consumption behaviour were significantly underrepresented. Conclusion: This analysis suggests that male gym users in the German population have a higher risk of excessive DS consumption than other subgroups. Awareness campaigns regarding the risk of intake and overconsumption of DS can be targeted to high-risk groups. Due to the small sample size and the different types of fitness gyms, further studies are needed to make clearer statements and identify more precise risk groups.

Educational outcomes school year nine in children treated for acute lymphoblastic leukemia: A nationwide registry-based study from Sweden.

Acute lymphoblastic leukemia (ALL) constitutes approximately 25% of pediatric cancers, and with contemporary protocols, the 5-year survival rate is over 90%. Despite improved survival, neurocognitive impairments from treatment raise concerns. This registry study aimed to explore the impact of ALL treatment on educational outcomes from school year nine in Swedish children. A population-based cohort of 503 children diagnosed with ALL from 1990 to 2010 was identified from the Swedish Childhood Cancer Registry and matched with five controls each. Assessed variables were delayed graduation, high school eligibility, total merit value, school grades in Swedish, English, mathematics, and physical education, and results in national tests. Analyses were performed between cases and controls and by sex, age at diagnosis, and risk group. Our results showed that, compared to controls, cases had higher odds for delayed graduation, poorer results in physical education, and higher rates of absence in national tests in English and mathematics. Children in the standard-risk group (treated with first-line chemotherapy only) exhibited similar results to matched controls whereas children in the high-risk group (treated with cranial irradiation, hematological stem cell transplantation, or/and for ALL relapse and thus likely received also radiotherapy) had lower total merit value compared to controls. We conclude that Swedish children diagnosed with ALL between the years 1990-2010 mainly exhibited comparable educational outcomes to controls, although children in the high-risk group had lower results. These findings highlight the importance of evaluating especially children with high-risk ALL in order to identify those requiring educational support and for designing targeted interventions.

Construction and validation of a prognostic model based on immune-metabolic-related genes in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC), a significant type of head and neck cancer, has witnessed increasing incidence and mortality rates. Immune-related genes (IRGs) and metabolic-related genes (MRGs) play essential roles in the pathogenesis, metastasis, and progression of OSCC. This study exploited data from The Cancer Genome Atlas (TCGA) to identify IRGs and MRGs related to OSCC through differential analysis. Univariate Cox analysis was utilized to determine immune-metabolic-related genes (IMRGs) associated with patient prognosis. A prognostic model for OSCC was constructed using Lasso-Cox regression and subsequently validated with datasets from the Gene Expression Omnibus (GEO). Non-Negative Matrix Factorization (NMF) clustering identified three molecular subtypes of OSCC, among which the C2 subtype showed better overall survival (OS) and progression-free survival (PFS). A prognostic model based on nine IMRGs was developed to categorize OSCC patients into high- and low-risk groups, with the low-risk group demonstrating significantly longer OS in both training and testing cohorts. The model showed strong predictive capabilities, and the risk score served as an independent prognostic factor. Additionally, expression levels of programmed death 1 (PD1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) differed between the risk groups. Gene Set Enrichment Analysis (GSEA) indicated distinct enriched pathways between high-risk and low-risk groups, highlighting the crucial roles of immune and metabolic processes in OSCC. The nine IMRGs prognostic model presented excellent predictive performance and has potential for clinical application.

Cardiovascular complications in COVID-19: acute management, long-term sequelae, and post-acute care strategies: a brief review

Background: The COVID-19 pandemic, driven by the SARS-CoV-2 virus, has significantly impacted individuals with pre-existing cardiovascular disease (CVD), elevating their risk of severe complications and mortality. Cardiovascular complications, such as myocarditis, acute coronary syndrome (ACS), arrhythmias, and venous thromboembolism (VTE), have been widely observed in COVID-19 patients, with mechanisms including viral myocardial injury, systemic inflammation, and a hypercoagulable state. These complications not only contribute to acute morbidity but also increase the risk of long-term cardiovascular sequelae, highlighting the need for optimized post-acute care in this population. Methods and Materials: A review was conducted based on a comprehensive search strategy using the PICO framework. Studies published from December 2019 onwards, focusing on COVID-19 patients with cardiovascular complications, were identified from databases including PubMed and Google Scholar. Objectives: This review aims to evaluate the cardiovascular complications of COVID-19, with particular attention to the acute and long-term management strategies. It seeks to assess whether comprehensive post-acute care programs tailored to cardiovascular health can reduce the incidence of long-term cardiovascular events and improve outcomes compared to standard care in COVID-19 survivors with pre-existing CVD. Discussion: The findings from this review underscore the significant cardiovascular burden faced by COVID-19 patients, particularly those with pre-existing conditions. Acute complications such as myocarditis, ACS, and VTE are common, with direct myocardial injury and systemic inflammation playing critical roles. Long-term sequelae, including persistent myocardial injury, heart failure, and arrhythmias, are increasingly being recognized, necessitating specialized post-acute care interventions. Evidence suggests that comprehensive cardiovascular rehabilitation programs incorporating lifestyle modification, pharmacotherapy optimisation, and regular monitoring may improve long-term outcomes. However, further research is required to establish the most effective management strategies, particularly for high-risk groups, such as patients with pre-existing CVD and pediatric populations.

Nomograms for predicting short-term mortality in acute-on-chronic liver disease caused by the combination of hepatitis B virus and alcohol.

This study aimed to identify predictive factors for the prognosis of acute-on-chronic liver disease (AoCLD) due to both hepatitis B virus (HBV) and alcohol and to develop prognostic models to improve treatment management. AoCLD patients with HBV and alcohol as etiological factors were selected from two multicenter prospective cohorts (NCT02457637,NCT03641872) and included in separate training and validation cohorts (n = 180 and n = 148). In the training cohort, the CATCH-LIFE A nomogram (based on age, bilirubin, international normalized ratio, serum sodium, and hepatic encephalopathy score) and CATCH-LIFE B nomogram (based on age, bilirubin, international normalized ratio, serum albumin, white blood cell, platelet count, and hepatic encephalopathy score) had discriminatory ability for predicting 28-day (c-indexes of 0.910 and 0.899) and 90-day mortality (c-indexes of 0.878 and 0.887, respectively). The area under the curve values for 28-day and 90-day mortality prediction by the CATCH-LIFE A nomogram were 0.922 (95% CI : 0.874, 0.971) and 0.905 (0.856, 0.956), respectively, while those for the CATCH-LIFE B nomogram were 0.916(0.861,0.972) and 0.915 (0.866,0.964), respectively. Similar performance results were observed in the validation cohort. Optimal cut-off scores for each nomogram could be used for patient stratification in high- and low-risk groups, and the high-risk groups showed shorter survival times than the low-risk groups in both the training and validation cohorts. Two nomograms constructed from the first short-term follow-up data from patients with AoCLD due to combined HBV infection and alcohol exposure showed good predictive performance for 28-day and 90-day mortality and might be used to guide clinical management.

Physical abuse by staff and co-residents of older people and people with intellectual disabilities

Summary Physical abuse in care settings is a social problem with detrimental effects for residents, but effective prevention is dependent on staff reporting. In Sweden, designated officials, commonly social workers, are required to investigate reports of mistreatment. The aim of this study was to analyze what designated officials considered serious in reported incidents of physical abuse in two different care settings: care for older people and care for people with intellectual disabilities. Similar cases of physical abuse were chosen to demonstrate differences between judgments and provide a picture of how designated officials judge the relative seriousness of abusive situations. Interpretative content analysis and analytic induction were used to analyze reports of staff-to-resident abuse and resident-to-resident abuse in the two care areas. Findings There were no differences between incidents described as serious and those described as non-serious. Resident-to-resident abuse was the most commonly reported incident, particularly in dementia care and care for people with intellectual disabilities, and was rarely considered serious. Older people in dementia care were the highest risk group. In staff-to-resident abuse, staff were singled out as scapegoats. Organizational issues, rather than the details of abusive incidents, guided investigators’ judgments of seriousness. Tendencies to normalize violence and apply a narrow understanding of violence were found in the investigator’s judgments, particularly in resident-to-resident abuse. Applications Safeguarding adults from physical abuse in institutional settings is dependent on staff reporting and thorough investigations. This study shows that more training in assessing violence for social workers investigating reports is needed.

Early pregnancy high normal HbA1c: a high risk group?

To determine if high normal early pregnancy HbA1c (35-40mmol/mol), in the absence of diabetes, was associated with increased risk of adverse perinatal outcomes compared to normal HbA1c (<35mmol/mol). A retrospective chart review was carried out on all singleton births in the Wellington region from 1 July 2019 to 31 December 2019. Exclusion criteria were participants domiciled outside the Wellington region, HbA1c ≥50mmol/mol, pre-existing diabetes, gestational diabetes in current pregnancy, no HbA1c performed <20 weeks or the first HbA1c was taken at ≥20 weeks. Baseline characteristics, HbA1c and pregnancy outcomes were obtained. The primary outcome was birth weight and was analysed using multiple linear regression. There were 1,067 participants in the normal HbA1c (nHbA1c) group and 186 in the high normal HbA1c (hnHbA1c) group. There was no difference in birth weight between hnHbA1c and nHbA1c. hnHbA1c had significantly lower odds of post-partum haemorrhage and composite maternal adverse outcomes compared to nHbA1c (OR 0.52, 95% CI 0.35-0.76) and (OR 0.64, 95% CI 0.46-0.89). High normal HbA1c was not associated with increased risk of adverse perinatal outcomes in pregnant people who did not develop gestational diabetes.

Construction of a disulfidptosis-associated lncRNAs risk model to predict prognosis and immuno-infiltration analysis of lung adenocarcinoma

Objective: To develop a risk model based on LncRNAs associated with disulfidptosis to forecast the prognosis and assess immune infiltration of Lung adenocarcinoma (LUAD). Methods: This study employed a bioinformatics approach. The study was conducted from March 29, 2023 and concluded on July 1, 2023 at Guangzhou University of Chinese Medicine, Guangzhou, China. Transcriptomic data specific to LUAD were collected from TCGA database. Disulfidptosis-related LncRNAs were preliminarily screened using co-expression analysis, followed by screening using Lasso regression and Cox regression to identify LncRNAs. Subsequently, prognostic prediction models were constructed. To assess the model, survival analysis, subject operating characteristic curves, and calibration curves were employed. To evaluate the tumor microenvironment, the “estimate” package was used, while the “ggpubr” package was utilized to visualize the variations. Additionally, we employed CIBERSORT to examine immune cell infiltration abundance. Results: A prognostic prediction model was constructed using five LncRNAs. The high-risk group displayed a shorter overall survival and progression-free survival (P&lt;0.05). The concordance index was calculated as 0.704 (95% CI: 0.654-0.754). GSEA analysis reveals that high risk group is associated with the cell cycle pathway and steroid hormone biosynthesis pathway, while the low-risk group is associated with hematopoietic cell pathway and allograft rejection pathway. Immune cell infiltration analysis indicated associations between the prognostic model and activated T cells CD4 memory, T cells CD8, etc. Conclusions: The risk model of Disulfidptosis-related LncRNAs can predict the prognosis of LUAD and evaluate the immune infiltration, providing a new direction for the treatment of LUAD. doi: https://doi.org/10.12669/pjms.40.10.9025 How to cite this: Liu J, Nie H, Du W, Song W. Construction of a disulfidptosis-associated lncRNAs risk model to predict prognosis and immuno-infiltration analysis of lung adenocarcinoma. Pak J Med Sci. 2024;40(10):2368-2372. doi: https://doi.org/10.12669/pjms.40.10.9025 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.