Subgroup Of Patients Research Articles

Polygenic Risk Assessment for Schizophrenia in Patients with Nonpsychotic Disorders and Attenuated Symptoms of Psychosis: A Pilot Study

Background: significant contribution of genetic factors in the development of schizophrenia is a generally recognized fact. Polygenic risk index for schizophrenia turned out to be an effective tool allowing to draw a dividing line between schizophrenia and mentally healthy control in terms of genetics. Objective: to assess the predictive ability of the polygenic risk score for schizophrenia (SZ-PRS) in adolescent patients with a first depressive episode and attenuated psychotic symptoms (APS). Patients and Methods: sixty adolescent inpatient with a first depressive episode were examined. Based on the presence of APS at admission, patients were divided into two groups: a group with APS and a group without APS. Subgroups of patients in the first group were identified through follow-up observations: those with psychosis manifestation and/or low social functioning and those without manifestation and with high social functioning. Whole-genome genotyping was performed for all participants, and SZ-PRS were calculated. For comparison, a group of patients diagnosed with schizophrenia (n = 879) and a group of mentally healthy individuals (n = 759), who had previously undergone whole-genome genotyping and had their SZ-PRS calculated, were used. Results: SZ-PRS of the APS group occupy an intermediate position between the healthy control and schizophrenia patients, significantly differing from each of them. The group without APS did not differ from the control group, but compared to the group of schizophrenia patients, the SZ-PRS in this group was significantly lower. Comparing subgroups of patients showed that the SZ-PRS in the APS group without psychosis manifestation and social functioning impairment was significantly lower than in the group with schizophrenia manifestation. The APS subgroups with psychosis manifestation and with functioning impairment did not differ significantly from each other or from the schizophrenia group. Conclusion: the results obtained for the first time for the russian population showed that SZ-PRS can be considered as a tool for assessing the risk of developing psychosis or reduced social functioning in patients with APS.

PRONA: An R-package for Patient Reported Outcomes Network Analysis

Abstract Summary Network analysis (NA) has recently emerged as a new paradigm by which to model the symptom patterns of patients with complex illnesses such as cancer. NA uses graph theory-based methods to capture the interplay between symptoms and identify which symptoms may be most impactful to patient quality of life and are therefore most critical to treat/prevent. Despite NA’s increasing popularity in research settings, its clinical applicability is hindered by the lack of a unified platform that consolidates all the software tools needed to perform NA, and by the lack of methods for capturing heterogeneity across patient cohorts. Addressing these limitations, we present PRONA, an R-package for Patient Reported Outcomes Network Analysis. PRONA not only consolidates previous NA tools into a unified, easy-to-use analysis pipeline, but also augments the traditional approach with functionality for performing unsupervised discovery of patient subgroups with distinct symptom patterns. Availability and Implementation PRONA is implemented in R. Source code, installation, and use instructions are available on GitHub at https://github.com/bbergsneider/PRONA. Supplementary information Supplementary information is available at Bioinformatics online.

Concomitant parasite infections influence tuberculosis immunopathology and favor rapid sputum conversion of pulmonary tuberculosis patients

Immunopathology of human tuberculosis (TB) in a subgroup of patients is characterized by aberrantly high concentrations of inflammatory cytokines, for example Interleukin (IL)-6. Concomitant (co-)infections by parasites can affect host immunity, but the impact on immunopathology in TB patients is poorly defined. Here we characterized a group of patients with TB ( n = 76) from Ghana with different protozoan and helminth co-infections. Plasma cytokines were measured at the onset of disease and anti-mycobacterial treatment efficacy was monitored during disease course. A subgroup of TB patients had co-infections with protozoan (n = 19) or helminth (n = 16) parasites. Plasma analyses for candidate cytokines identified lower levels of IL-6 in parasite co-infected patients with TB. Moreover, it took less time for co-infected patients to become sputum-negative for Mycobacterium tuberculosis during treatment. These results indicated an influence of parasite co-infections on immunopathology in TB and suggested positive effects on treatment efficacy.

Heterogeneous Treatment Effects of High-Frequency Oscillatory Ventilation for Acute Respiratory Distress Syndrome: A Post Hoc Analysis of the Oscillation for Acute Respiratory Distress Syndrome Treated Early (OSCILLATE) Trial

OBJECTIVES: We sought to evaluate whether different subgroups of adults with acute respiratory distress syndrome (ARDS) respond differently to high-frequency oscillatory ventilation (HFOV). DESIGN: The Oscillation for ARDS Treated Early (OSCILLATE) trial was a randomized controlled trial of HFOV vs. conventional ventilation that found an increased risk of in-hospital mortality (primary outcome) with HFOV. In a post hoc analysis, we applied three different approaches to evaluate heterogeneity of treatment effect for in-hospital mortality: 1) subgroup analyses based on baseline Pao 2:Fio 2 ratio and oxygenation index (OI); 2) a risk-based approach using a multivariable outcome prediction model; and 3) a clustering approach via multivariable latent class analysis. We used multivariable logistic regression models to assess for interaction. SETTING: Thirty-nine ICUs, five countries. SUBJECTS: Five hundred forty-eight adults with moderate to severe ARDS. INTERVENTIONS: HFOV vs. conventional mechanical ventilation with low tidal volume and higher positive end-expiratory pressure. MEASUREMENTS AND MAIN RESULTS: The effect of HFOV on in-hospital mortality was consistent across categories of Pao 2:Fio 2 ratio (adjusted odds ratio [aOR], 2.04; 95% CI, 1.32–3.17 and aOR, 1.16; 95% CI, 0.49–2.75 for groups with Pao 2:Fio 2 above or equal to 80, vs. below 80, respectively; interaction p = 0.23) and OI (aOR, 1.78; 95% CI, 0.67–4.70; aOR, 3.19; 95% CI, 1.44–7.09; aOR, 1.73; 95% CI, 0.82–3.65; and aOR, 1.33; 95% CI, 0.61–2.90 for quartiles of baseline OI, respectively; interaction p = 0.44). Point estimates for the effect of HFOV were consistent across risk categories (aOR, 2.44; 95% CI, 0.40–14.83; aOR, 1.69; 95% CI, 0.75–3.85; and aOR, 2.10; 95% CI, 0.59–7.54 for the lowest, moderate, and highest risk categories, respectively; interaction p = 0.32). Using a clustering approach, point estimates for HFOV were also consistent (cluster 1: aOR, 1.85; 95% CI, 1.15–3.00 and cluster 2: aOR, 1.75; 95% CI, 0.91–3.38; interaction p = 0.75). CONCLUSIONS: We did not identify heterogeneity in the effect of HFOV across different subgroups of patients with ARDS.

Performance of Risk Models for Antimicrobial Resistance in Adult Patients With Sepsis

ImportanceThe results of prediction models that stratify patients with sepsis and risk of resistant gram-negative bacilli (GNB) infections inform treatment guidelines. However, these models do not extrapolate well across hospitals.ObjectiveTo assess whether patient case mix and local prevalence rates of resistance contributed to the variable performance of a general risk stratification GNB sepsis model for community-onset and hospital-onset sepsis across hospitals.Design, Setting, and ParticipantsThis was a retrospective cohort study conducted from January 2016 and October 2021. Adult patients with sepsis at 10 acute-care hospitals in rural and urban areas across Missouri and Illinois were included. Inclusion criteria were blood cultures indicating sepsis, having received 4 days of antibiotic treatment, and having organ dysfunction (vasopressor use, mechanical ventilation, increased creatinine or bilirubin levels, and thrombocytopenia). Analyses were completed in April 2024.ExposureThe model included demographic characteristics, comorbidities, vital signs, laboratory values, procedures, and medications administered.Main Outcomes and MeasuresCulture results were stratified for ceftriaxone-susceptible GNB (SS), ceftriaxone-resistant but cefepime-susceptible GNB (RS), and ceftriaxone- and cefepime-resistant GNB (RR). Negative cultures and other pathogens were labeled SS. Deep learning models were developed separately for community-onset (patient presented with sepsis) and hospital-onset (sepsis developed ≥48 hours after admission) sepsis. The models were tested across hospitals and patient subgroups. Models were assessed using area under the receiver operating characteristic curve (AUROC) and area under precision recall curve (AUPRC).ResultsA total of 39 893 patients with 85 238 sepsis episodes (43 207 [50.7%] community onset; 42 031 [48.3%] hospital onset) were included. Median (IQR) age was 65 (54-74) years, 21 241 patients (53.2%) were male, and 18 830 (47.2%) had a previous episode of sepsis. RS contributed to 3.9% (1667 episodes) and 5.7% (2389 episodes) of community-onset and hospital-onset sepsis episodes, respectively, and RR contributed to 1.8% (796 episodes) and 3.9% (1626 episodes), respectively. Previous infections and exposure to antibiotics were associated with the risk of resistant GNB. For example, in community-onset sepsis, 375 RR episodes (47.1%), 420 RS episodes (25.2%) and 3483 of 40 744 (8.5%) SS episodes were among patients with resistance to antimicrobial drugs (P < .001). The AUROC and AUPRC results varied across hospitals and patient subgroups for both community-onset and hospital-onset sepsis. AUPRC values correlated with the prevalence rates of resistant GNB (R = 0.79; P = .001).Conclusions and RelevanceIn this cohort study of 39 893 patients with sepsis, variable model performance was associated with prevalence rates of antimicrobial resistance rather than patient case mix. This variability suggests caution is needed when using generalized models for predicting resistant GNB etiologies in sepsis.

Is Adjuvant Therapy Necessary for Stage IB Gastric Cancer: A Retrospective Cohort Study

Abstract Background The benefit of adjuvant therapy for patients with IB gastric cancer (GC) is a topic of debate. This study aimed to evaluate the benefit of adjuvant therapy for patients with IB GC. Methods Overall, the study selected 510 IB GC patients after gastrectomy at the First Medical Center of the Chinese PLA General Hospital, Beijing, China between 2005 and 2018. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method and the log-rank test. Cox regression analyses were used to confirm the independent prognostic factors. Results Patients who received postoperative adjuvant therapy had a longer 5-year OS (92.9 %) than those who received surgery alone (86.7 %; P < 0.05), but the 5-year DFS did not differ significantly between the two groups (92.6 vs. 95.0 %; P > 0.05). Moreover, DFS did not differ between monotherapy, and combination therapy. Uni- and multivariate analyses showed that older age was a significant risk factor for tumor recurrence. Subgroup analyses also failed to identify suitable candidates for chemotherapy. Conclusions Because adjuvant therapy did not demonstrate any benefits in terms of tumor recurrence or DFS, these treatment strategies may be unnecessary for IB GC patients after gastrectomy. Further studies are required to identify subgroups of IB GC patients who may benefit from adjuvant treatments.

Effects of antipsychotic drugs during radiotherapy in breast cancer in South Korea: a retrospective cohort study

In this study, we aimed to investigate the nationwide utilization of antipsychotic drugs (APDs) during radiotherapy and evaluate their association with survival in patients with breast cancer. This retrospective cohort study used the National Health Insurance Service database in Korea and included patients diagnosed with breast cancer from 2010 to 2020 who received radiotherapy. The APDs included in the analysis were aripiprazole, quetiapine, olanzapine, risperidone, haloperidol, and chlorpromazine, and the APD prescription details included prescription time, dosage, and duration. Among 170,226 patients with breast cancer treated with radiotherapy, 3361 (1.97%) received APD during radiotherapy. Use of APDs was significantly associated with higher mortality in all patients and in a subgroup of patients excluding those with metastasis or other cancers. Among patients taking APD during radiotherapy, those with accompanied psychiatric history and long-term APD use for ≥ 3 months were associated with lower mortality, whereas patients who started APD during radiotherapy had higher mortality than those who started APD before radiotherapy. The high mortality observed in breast cancer patients using APDs during radiotherapy could be influenced by the underlying conditions that necessitated APD use. Further studies are needed to determine the effects of APDs during radiotherapy in patients with breast cancer.

Differentiating HER2-low and HER2-zero tumors with 21-gene multigene assay in 2,295h + HER2- breast cancer: a retrospective analysis.

HER2-positivity is an essential marker for therapeutic decisions, while HER2 expression is heterogenous. In recent years, there has been increasing recognition of a subgroup of breast cancer patients who have low levels of HER2 expression, also known as HER2-low because trastuzumab deruxtecan offers clinical benefit for patients with HER2-low metastatic breast cancer. Despite the growing interest in HER2-low breast cancer, there is limited research on how multigene assays can help differentiate between HER2-low and HER2-negative breast cancer. Among HR + HER2- breast cancer, we compared genomic characteristics between HER2-low and HER2-zero using the 21-gene assay. A retrospective review of clinical records was performed in 2,295 patients who underwent Oncotype DX® test in two hospitals between 2013 and 2020. Patients were classified into two groups as the HER2-zero and HER2-low based on HER2 immunohistochemistry. In cases with HER2 2+, no amplification of HER2 gene was confirmed by silver in situ hybridization. High genomic risk was defined as cases with 21-gene recurrence score (RS) > 25. Multivariable binary logistic-regression analysis was performed. Of these, 944 (41.1%) patients were assigned to the HER2-zero group, while 1351 (58.9%) patients were assigned to the HER2-low group. The average Recurrence Score (RS) was found to be 17.802 in the HER2-zero breast cancer group and 18.503 in the HER2-low group, respectively (p-value < 0.005). When comparing the proportion of high RS between the two groups, the HER2-zero group had a high RS rate of 12.4% (117 out of 944), while the HER2-low group had a high RS rate of 17.0% (230 out of 1351) (p = 0.002). The HER2 score identified by qRT-PCR was 8.912 in the HER2-zero group and 9.337 in the HER2-low group (p < 0.005). In multivariable analysis, HER2-low status was found to be an independent factor for high RS, with an odds ratio of 1.517 (1.172-1.964), independent of ER, PR, and Ki67. Within the subgroup of patients with invasive ductal carcinoma, the high RS rates were 19% in the HER2-low group and 14% in the HER2-zero group. However, when considering all patients, there were no significant differences observed in recurrence-free survival and overall survival between the HER2-low and HER2-zero groups. Within HR + HER2- breast cancer, HER2-low tumors are associated with high RS, especially for histologically invasive ductal carcinoma. A prognostic influence of HER2-low expression among HR + HER2- breast cancer remains as an area that requires further study.

Neuroendocrine tumours and pregnancy: Real-world data from an European Neuroendocrine Tumour Centre of Excellence.

Neuroendocrine neoplasms (NENs) arise from the diffuse endocrine system and have been considered to be rare. However, the incidence and prevalence of these tumours have increased in recent years, and they are being seen in younger patients including women in the reproductive age group. Due to the paucity of data, diagnostic and therapeutic strategies in managing such tumours during pregnancy can be challenging to both treating physicians and patients. This article describes the experience and outcomes of managing pregnant women with NEN at a European Neuroendocrine Tumour Society (ENETS) Centre of Excellence. In this retrospective analysis, we evaluated a total of 22 pregnancies in 18 pregnant women with concurrent diagnoses of NENs who were managed at Royal Free Hospital ENETS Centre of Excellence throughout their pregnancy. These were identified from our tumour registry of 3500 NEN patients between 2015 and 2023. Cross-sectional imaging (computed tomography (CT)/magnetic resonance imaging (MRI)), pre- and post-pregnancy, for each patient was reviewed by an experienced radiologist. Tumour growth rate (TGR) was calculated using the formula: TGR = 100 × [exp (TG) - 1]; TG. [3 × log (D2/D1)]/time (months), where D1 is the tumour size at date 1; D2 is the tumour size at date 2; and time (months) = (Date 2 - Date 1 + 1)/30.44. Tumour growth rate pre-conception (TGRpc) and tumour growth rate post-partum (TGRpp) were calculated for each patient. In a sub-group of patients, positivity for oestrogen and progesterone receptors were analysed on the tumour tissue to evaluate whether the presence of these receptors affected tumour progression during the pregnancy. We also reviewed the pregnancy outcome in patients treated with somatostatin analogues during pregnancy. We analysed the data of a total 22 pregnancy encounters in 18 women: 15 pregnancies (68%) preceded the diagnosis of the NEN, whereas the diagnosis of NEN was made during pregnancy or in the post-partum period in 5 (23%) and 2 (9%) pregnancies respectively. Eight patients (44%) had a diagnosis of a pancreatic NEN, whereas 5 (28%) were diagnosed with mid-gut NENs, and a further 5 at other sites. The majority of the patients (n = 12, 67%) had evidence of metastatic disease at the time of diagnosis. Most pregnancies had a successful outcome (n = 19, 86%), whereas 3 patients (14%) had miscarriages in the 1st trimester. Five patients in total of 6 pregnancies were treated with somatostatin analogues as monotherapy during the pregnancy, and all of them had stable disease after pregnancy. All of them delivered healthy babies without any side effects or complications due to therapy. The average TGRpc was -0.8% (n = 5) and the average TGRpp was +0.96% (n = 6); 2 patients who did not have suitable targets for calculation of TGRpc developed new lesions suggesting disease progression. Moreover, 2 of the 4 patients who have had both pre-conception and post-pregnancy scans showed an increase in TGRpp compared to TGRpc. The management of NENs during pregnancy should be multidisciplinary with an individualised approach to each patient. Somatostatin analogues appear to be safe during pregnancy, though further robust studies are needed. Pregnancy per se may accelerate tumour progression, and patients should be counselled regarding this possibility.

Risk Score for Hepatocellular Cancer in Adults Without Viral Hepatitis or Cirrhosis

Hepatocellular carcinoma (HCC) is typically detected only at advanced stages when treatment options are limited. Most of the current HCC risk models focus on patients with viral hepatitis or diagnosed cirrhosis or require variables not routinely available in clinical care. To identify modifiable HCC risk factors in the general population and to develop a risk score to inform HCC screening and risk-factor modification interventions for high-risk individuals without viral hepatitis or decompensated cirrhosis. This cohort study analyzed demographic, clinical, laboratory, and diagnostic data from the US Department of Veterans Affairs (VA) electronic health records. Data were divided into development and validation samples. Veterans aged 30 to 95 years were included, and those with hepatitis B or C virus infection, hepatic decompensation, or prevalent HCC were excluded. Patients were followed up until the occurrence of HCC diagnosis, death, or December 31, 2021. A Cox proportional hazards regression model for 10-year risk of HCC was developed and used to create an HCC risk score, and performance in development and validation samples and in patient subgroups was evaluated. One outpatient visit date per person at least 18 months after VA entry, between October 1, 2007, and March 31, 2020, was randomly selected and used as the index date for the start of follow-up. Analyses were performed from March 2023 to May 2024. Age, sex, race and ethnicity, body mass index, liver fibrosis (detected with Fibrosis-4 Index [FIB-4]), diabetes status, smoking status, and alcohol use. First HCC diagnosis during follow-up. This information was ascertained from VA national cancer registry topography and histology codes and from International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes for the inpatient or outpatient visits. This study of 6 509 288 veterans included 6 048 917 males (92.9%), with a median (IQR) age of 65 (54-74) years, who identified as being of Hispanic (5.3%), non-Hispanic Black (15.0%), non-Hispanic White (68.9%), or other (4.6%) race and ethnicity. Overall, 15 142 patients (0.2%) developed HCC, 69.5% of whom had FIB-4 of 3.25 or lower at baseline. While FIB-4 was the most important variable, age, sex, race and ethnicity, body mass index, diabetes, smoking, and alcohol use were also informative. Discrimination in the development sample was better than FIB-4 alone (C statistic, 0.83 [95% CI, 0.82-0.85] vs 0.79 [95% CI, 0.77-0.80]). The HCC risk score performed consistently well in the validation sample and in all subgroups. A FIB-4 threshold of 3.25 would screen 5.0% of the cohort at a cost of 28 false-positives for every true-positive; a model risk score of 58 would screen 4.7% of the cohort at a cost of 23 false-positives for every true-positive. Results of this study suggest that a multivariable risk score that uses routinely available clinical data outperforms FIB-4 alone in identifying patients at risk of HCC who do not have viral hepatitis or hepatic decompensation at baseline.

A proliferation-inducing ligand (APRIL) level among risk factors of ocular involvement in patients with Behçet’s disease

IntroductionOcular involvement is quite common in Behçet’s disease (BD) and may cause crucial functional complications. Even though the mechanisms of BD remain unclear, advances in gene­tic and immunological fields have improved our understanding of the immunopathogenesis of BD ocular involvement. Little is known about the expression of a proliferation-inducing ligand (APRIL) in terms of ocular involvement in BD. The objective of this study was to determine whether serum APRIL concentrations are associated with ocular involvement in patients with BD.Material and methodsThe study included 60 patients diagnosed with BD matched by age and sex to 30 healthy individuals. Every patient underwent a clinical evaluation, and the Behçet’s Disease Current Activity Form (BDCAF) was utilized to quantify disease activity. All patients underwent a comprehensive ophthalmological assessment. Serum APRIL was assessed for patients as well as controls.ResultsOne or more ocular manifestations were found in 42 BD patients (70%), while 18 patients (30%) had no ocular involvement. The mean level of serum APRIL levels was markedly elevated in BD patients, particularly those with ocular involvement, compared to both BD patients without ocular involvement and healthy individuals. A statistically significant association was determined between high APRIL concentration and development of uveitis, cataract, and hypopyon. Cutaneous lesions and arthritis were strong independent predictors for ocular involvement in BD patients.ConclusionsOverexpression of APRIL in patients with BD, particularly in terms of uveitis, cataract, and hypopyon, lends credence to the idea that B cell activating factors have an important function in BD. These findings may indicate that serum APRIL concentrations can differentiate a clinical subgroup of BD patients with ocular disease. As a result, finding a new therapeutic strategy targeting the APRIL pathway might be beneficial in BD patients suffering from ocular involvement.

Enhancing Coronary Revascularization Decisions: The Promising Role of Large Language Models as a Decision-Support Tool for Multidisciplinary Heart Team.

While clinical practice guidelines advocate for multidisciplinary heart team (MDHT) discussions in coronary revascularization, variability in implementation across health care settings remains a challenge. This variability could potentially be addressed by language learning models like ChatGPT, offering decision-making support in diverse health care environments. Our study aims to critically evaluate the concordance between recommendations made by MDHT and those generated by language learning models in coronary revascularization decision-making. From March 2023 to July 2023, consecutive coronary angiography cases (n=86) that were referred for revascularization (either percutaneous or surgical) were analyzed using both ChatGPT-3.5 and ChatGPT-4. Case presentation formats included demographics, medical background, detailed description of angiographic findings, and SYNTAX score (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery; I and II), which were presented in 3 different formats. The recommendations of the models were compared with those of an MDHT. ChatGPT-4 showed high concordance with decisions made by the MDHT (accuracy 0.82, sensitivity 0.8, specificity 0.83, and kappa 0.59), while ChatGPT-3.5 (0.67, 0.27, 0.84, and 0.12, respectively) showed lower concordance. Entropy and Fleiss kappa of ChatGPT-4 were 0.09 and 0.9, respectively, indicating high reliability and repeatability. The best correlation between ChatGPT-4 and MDHT was achieved when clinical cases were presented in a detailed context. Specific subgroups of patients yielded high accuracy (>0.9) of ChatGPT-4, including those with left main disease, 3 vessel disease, and diabetic patients. The present study demonstrates that advanced language learning models like ChatGPT-4 may be able to predict clinical recommendations for coronary artery disease revascularization with reasonable accuracy, especially in specific patient groups, underscoring their potential role as a supportive tool in clinical decision-making.

Occupational Physical Activity and Regular Exercise Are Inversely Correlated with Thyroid Function in Patients with Hashimoto’s Thyroiditis

Objective: We evaluated correlations of occupational physical activity (OPA) and recreational exercise (RE), respectively, with thyroid function in patients with Hashimoto’s thyroiditis (HT). Methods: We included 438 individuals with clinically diagnosed HT. Information on OPA and RE were collected through a self-report questionnaire. We assessed correlations between clinical phenotypes (TSH, T3, T4, fT4, TgAb, TPOAb, thyroid volume, vitamin D) and physical activities (OPA and RE) in all HT patients (ALL) and in two severity-based subgroups of patients (MILD and OVERT). Results: The main novel findings are significant correlations between increase in OPA and (i) a decrease in fT4 (OVERT, r = −0.265, p = 0.0002 and ALL, r = −0.138, p = 0.006); (ii) an increase in TSH (ALL, r = 0.124, p = 0.014 and OVERT, r = 0.183, p = 0.013) and (iii) an increase in TPOAb antibodies (ALL, r = 0.101, p = 0.045). In contrast, we observed correlations between increase in RE and: (i) a decrease in TSH (OVERT, r = −0.238, p = 0.001); (ii) a decrease in TgAb antibodies (OVERT, r = −0.194, p = 0.01) and (iii) an increase in vitamin D levels (ALL, r = 0.146, p = 0.005 and OVERT, r = 0.173, p = 0.023). Conclusions: Our results suggest that, unlike RE, OPA correlates with decreased thyroid function and increased thyroid autoimmunity. Our study proposes that the PA health paradox also applies for the thyroid health.

Impact of Precision in Staging Acute Kidney Injury and Chronic Kidney Disease on Treatment Outcomes: An Observational Study

(1) Background: “Kidney Disease: Improving Global Outcomes” (KDIGO) provides guidelines for identifying the stages of acute kidney injury (AKI) and chronic kidney disease (CKD). A data-driven rule-based engine was developed to determine KDIGO staging compared to KD-related keywords in discharge letters. (2) Methods: To assess potential differences in outcomes, we compare the patient subgroups with exact KDIGO staging to imprecise or missing staging for all-cause mortality, in-hospital mortality, selection bias and costs by applying Kaplan–Meier analysis and the Cox proportional hazards regression model. We analysed 63,105 in-patient cases from 2016 to 2023 at a tertiary hospital with AKI, CKD and acute-on-chronic KD. (3) Results: Imprecise and missing CKD staging were associated with an 85% higher risk of all-cause and in-hospital mortality (CI: 1.7 to 2.0 and 1.66 to 2.03, respectively) compared to exact staging for any given disease status; imprecise or missing AKI staging increased in-hospital mortality risk by 56% and 57% (CI: 1.43 to 1.70 and 1.37 to 1.81, respectively) in patients with AKI. (4) Conclusions: Exact staging is associated with better outcomes in KD management. Our study provides valuable insight into potential quality and outcome improvements and lower costs, considering elderly patients, women and patients with acute-on-chronic KD as the most vulnerable.

Perfluorohexyloctane ophthalmic solution for dry eye disease: pooled analysis of two phase 3 clinical trials

BackgroundDry eye disease (DED) is commonly caused by excessive tear film evaporation due to Meibomian gland dysfunction (MGD). There is a need for DED treatment options that address tear evaporation and benefit patients across a broad range of demographic and disease characteristics. This study evaluated treatment effects of perfluorohexyloctane ophthalmic drop (formerly NOV03) in the pooled dataset from 2 pivotal clinical trials in patients with DED associated with MGD, both in the overall population and in patient subgroups based on sex, age, and baseline severity of eye dryness.MethodsPooled data from 2 similarly designed, phase 3, randomized controlled trials (GOBI, MOJAVE) were analyzed. Patients aged ≥18 years with DED administered perfluorohexyloctane (n=614) or hypotonic (0.6% solution) saline control (n=603) four times daily for 8 weeks. Primary endpoints were total corneal fluorescein staining (tCFS) score (National Eye Institute scale, 0-15) and eye dryness visual analog scale (VAS) score (0-100). Efficacy was evaluated using analysis of covariance among patient subgroups (male and female, older [≥65 years] and younger [18 to &amp;lt;65 years], tCFS score &amp;lt;7 and ≥7, VAS eye dryness score &amp;lt;70 and ≥70, MGD score &amp;lt;7 and ≥7, Schirmer I test &amp;lt;10 mm and ≥10 mm).ResultsReductions in tCFS and VAS eye dryness scores were greater for perfluorohexyloctane versus control. In the overall patient population, least-squares mean treatment difference was −1.1 (95% CI: −1.41 to −0.79; p&amp;lt;0.0001) for tCFS and −9.0 (95% CI: −11.90 to −6.00; p&amp;lt;0.0001) for VAS eye dryness. Treatment favored perfluorohexyloctane over control in all patient subgroup analyses of tCFS and VAS eye dryness. Overall, the most common adverse event with perfluorohexyloctane was blurred vision (2.1% of patients), which was mild and transient.ConclusionsCompared with a hypotonic saline control, perfluorohexyloctane improved both the signs and symptoms of DED, including in patients with greater self-reported severity of eye dryness.Clinical trial registrationThis study represents an integrated analysis of 2 previous clinical trials: GOBI (ClinicalTrials.gov, NCT04139798) and MOJAVE (ClinicalTrials.gov, NCT04567329).

Labour market participation and income in patients with IBD onset before young adulthood - the role of disease severity and mental health.

Only few studies have examined the socioeconomic consequences of being diagnosed with inflammatory bowel disease (IBD) in childhood or youth. Disease severity has been linked to lower earnings, but little attention has been paid to comorbid mental health conditions. The aim is to examine labour market participation (LMP) and income in patients with IBD-onset in childhood or youth and examine how disease severity and mental health conditions affects LMP. In this register-based cohort study, we included patients with IBD-onset before 25 years of age and matched comparators. We estimated the relative risk (RR) of having low LMP and the median yearly income from ages 26 to 30. RR of low LMP was also assessed in subgroups of patients based on disease severity (severe/non-severe) and mental health conditions (yes/no). A total of 3,398 patients with IBD and 28,207 comparators were included. Overall, patients with IBD more often had low LMP (16.4% vs 14.4% in comparators), but slightly higher income (median yearly income difference at age 30: 1,141 Euro [95% CI: 483-1,798]). In subgroup analyses, only patients with severe IBD had higher risk of low LMP (RR 1.46 [95% CI 1.23-1.72]), not patients with non-severe IBD. Among patients with severe disease and mental health conditions 46% had low LMP (RR 5.03 [95% CI 4.38-5.78]). Patients with IBD more often had low LMP, but their income was not affected. The subgroup of patients with severe disease and mental health conditions had the highest risk of low LMP.

How to prevent postextubation respiratory failure

Purpose of review Postextubation respiratory support treatment approaches, indications, and subgroups of patients with different responses to those therapies are rapidly changing. Planning optimal therapy in terms of choosing devices, timing of application and selecting settings with the goal of minimizing extubation failure is becoming a challenge. This review aims to analyze all the available evidence from a clinical point of view, trying to facilitate decision making at the bedside. Recent findings There is evidence for high flow nasal cannula support in patients at low risk of extubation failure. Noninvasive ventilation based strategies should be prioritized in patients at very high risk, who are obese or are hypercapnic at the end of a spontaneous breathing trial. Patients not included in the previous groups merit a tailored decision based on more variables. Optimizing the timing of therapy can include facilitation of extubation by transitioning to noninvasive respiratory support or prolonging a planned preventive therapy according to clinical condition. Summary Planning postextubatin respiratory support must consider the risk for failing and the presence of some clinical conditions favoring noninvasive ventilation. Extubation can be safely accelerated by modifying screening criteria and spontaneous breathing trial settings, but there is room to increase the role of postextubation noninvasive respiratory support for this indication, always keeping in mind the dangers of delaying a needed intubation.

Male fertility is preserved following ixekizumab treatment-a real life pilot study.

Preserving fertility is crucial when managing male patients with spondyloarthritis (SpA) and/or psoriasis (PsO), especially in young men. Chronic inflammation, hormonal dysregulation, and immunosuppressive therapies can negatively impact male fertility. Over the past decades, positive data have emerged regarding the reproductive safety of various therapies in men. Ixekizumab (IXE), a high-affinity monoclonal antibody targeting IL-17A, has shown a safe profile for male fertility in small studies. This pilot study assesses the impact of IXE treatment on sperm parameters in SpA and/or PsO patients in a real-world setting. Consecutive adult male SpA and/or PsO patients eligible for or undergoing IXE treatment were prospectively enrolled. Demographic data, disease characteristics, laboratory assessments, comorbidities, and previous treatments were recorded. Sperm analysis was conducted after a minimum of 6 months of IXE treatment, and also before treatment inititation in a subgroup of patients. Parallel sperm evaluations were performed in a control group of healthy donors. Ten patients were enrolled: 8 with SpA and 2 with PsO. After 6 months of IXE treatment, all patients had normal sperm parameters. One SpA and PsO patient with baseline oligozoospermia showed normal parameters at follow-up and achieved a successful pregnancy post-treatment. Compared with controls, IXE-treated patients had lower sperm concentrations but higher vitality. In our limited size pilot study on SpA and PsO patients, Ixekizumab exposure did not impair male fertility. Sperm parameters remained within normal ranges after a minimum of 6 months of treatment. Early Ixekizumab treatment may preserve or potentially reverse fertility impairment.

The Effect of Vitamin D Supplementation Post COVID-19 Infection and Related Outcomes: A Systematic Review and Meta-Analysis

Background: Vitamin D’s role in COVID-19 management remains controversial. This meta-analysis aimed to evaluate the efficacy of vitamin D supplementation in patients with SARS-CoV-2 infection, focusing on mortality, intensive care unit (ICU) admissions, intubation rates, and hospital length of stay (LOS). Methods: A systematic review of PubMed/MEDLINE, Scopus, Cochrane, and Google Scholar databases was conducted. Randomized controlled trials (RCTs) and analytical studies investigating vitamin D supplementation in COVID-19 patients were included. The meta-analysis was performed using STATA MP 18.5, employing random-effect or fixed-effect models based on heterogeneity. Results: Twenty-nine studies (twenty-one RCTs, eight analytical) were analyzed. Vitamin D supplementation significantly reduced ICU admissions (OR = 0.55, 95% CI: 0.37 to 0.79) in RCTs and analytical studies (OR = 0.35, 95% CI: 0.18 to 0.66). Intubation rates were significantly reduced in RCTs (OR = 0.50, 95% CI: 0.27 to 0.92). Mortality reduction was significant in analytical studies (OR = 0.45, 95% CI: 0.24 to 0.86) but not in RCTs (OR = 0.80, 95% CI: 0.61 to 1.04). Subgroup analyses revealed more pronounced effects in older patients and severe COVID-19 cases. LOS showed a non-significant reduction (mean difference = −0.62 days, 95% CI: −1.41 to 0.18). Conclusions: This meta-analysis suggests potential benefits of vitamin D supplementation in COVID-19 patients, particularly in reducing ICU admissions. However, the evidence varies across outcomes and patient subgroups. Discrepancies between RCTs and analytical studies highlight the need for further large-scale, well-designed trials accounting for baseline vitamin D status, standardized supplementation protocols, and patient characteristics to inform clinical guidelines for vitamin D use in COVID-19 management.

Chronic low-grade inflammation in patients with systemic sclerosis is associated with increased risk for arteriosclerotic cardiovascular disease

BackgroundVasculopathy is a hallmark of systemic sclerosis (SSc) putting patients at an increased risk of cardiovascular disease. Approximately 20–25% of all SSc patients show prolonged elevated C-reactive protein (CRP) levels and thus signs of chronic low-grade inflammation. While CRP−positivity is an independent predictor of cardiovascular disease in non-SSc populations, the relationship between CRP−positivity and cardiovascular health/atherosclerosis in SSc patients is only incompletely understood. Here, we aimed to assess (1) which general, SSc disease-specific and cardiovascular parameters are associated with CRP−positivity in a cohort of SSc patients with prolonged CRP elevations (CRP+ SSc group) relative to SSc patients without CRP elevations (CRP− SSc group). In addition (2), we aimed to investigate whether prolonged CRP−positivity in SSc patients is associated with a higher cardiovascular risk and an increased atherosclerotic burden. We also aimed to (3) identify via random forest classification modeling which combined cardiovascular and/or SSc-specific parameters could differentiate best between SSc patients with elevated CRP levels (the so-called “inflammatory SSc subtype”) and SSc patients without increased CRP levels.MethodsSixty-five SSc patients were recruited and assigned to the CRP+ SSc group (n = 20) if their CRP levels were &amp;gt; 5 mg/L in at least three half-yearly visits within 2 years before enrolment or to the CRP− SSc group (n = 45), respectively. All patients underwent an anamnesis, physical examination, blood draw, and bilateral carotid ultrasound in order to assess arteriosclerotic burden including the presence, number and height of plaques, and carotid intima–media thickness (CIMT) as well as lipid profiles. 10-year ASCVD risk was estimated via the ASCVD risk estimator plus. Statistical evaluation included Spearman’s correlations, logistic regression and random forest modeling under 5-fold cross-validation, and permutation testing to determine combinations of cardiovascular variables highly discriminatory for CRP−positivity.ResultsSSc groups showed comparable mean age, height, and extent of SSc organ involvement. Regarding cardiovascular health, CRP+ SSc patients exhibited a significantly altered HDL-, LDL-, and triglyceride profile (0.001 ≤ p ≤ 0.017) and a significantly higher 10-year ASCVD risk (p = 0.047), relative to CRP− SSc patients. Additionally, within the subgroup of CRP+ SSc patients, positive correlations between CRP levels and CIMT right (ρ = 0.657, p = 0.002) and mean CIMT left and right (ρ = 0.497, p = 0.026) were seen. Combined ROC models identified the four lipid components (HDL, LDL, total cholesterol, and triglycerides) or the SSc duration and ASCVD category to differentiate with high cross-validated ROC-AUCs (AUC: 0.83 ± 0.15, and AUC: 0.86 ± 0.09, p &amp;lt; 0.001) for prolonged CRP−positivity among SSc patients.ConclusionOur data indicate that persistent CRP−positivity and thus chronic low-grade inflammation in SSc patients enhance the risk for arteriosclerotic-cardiovascular disease significantly beyond the ASCVD risk observed for our SSc patients without CRP elevations. It seems to be along with a disrupted lipid profile the hallmark of a distinct “inflammatory” subgroup of SSc patients. However, large population-based studies and clinical trials in patients with SSc are needed to validate our findings in a prospective or interventional setting.