Adult Patients Research Articles

Predicting response to neoadjuvant chemotherapy for colorectal liver metastasis using deep learning on prechemotherapy cross-sectional imaging.

Deep learning models (DLMs) are applied across domains of health sciences to generate meaningful predictions. DLMs make use of neural networks to generate predictions from discrete data inputs. This study employs DLM on prechemotherapy cross-sectional imaging to predict patients' response to neoadjuvant chemotherapy. Adult patients with colorectal liver metastasis who underwent surgery after neoadjuvant chemotherapy were included. A DLM was trained on computed tomography images using attention-based multiple-instance learning. A logistic regression model incorporating clinical parameters of the Fong clinical risk score was used for comparison. Both model performances were benchmarked against the Response Evaluation Criteria in Solid Tumors criteria. A receiver operating curve was created and resulting area under the curve (AUC) was determined. Ninety-five patients were included, with 33,619 images available for study inclusion. Ninety-five percent of patients underwent 5-fluorouracil-based chemotherapy with oxaliplatin and/or irinotecan. Sixty percent of the patients were categorized as chemotherapy responders (30% reduction in tumor diameter). The DLM had an AUC of 0.77. The AUC for the clinical model was 0.41. Image-based DLM for prediction of response to neoadjuvant chemotherapy in patients with colorectal cancer liver metastases was superior to a clinical-based model. These results demonstrate potential to identify nonresponders to chemotherapy and guide select patients toward earlier curative resection.

DORIS study: domestic violence in orthopaedics, a prospective cohort study at a Swedish hospital on the annual prevalence of domestic violence in orthopaedic emergency care

BackgroundDomestic violence (DV) is a major problem which despite many efforts persists globally. Victims of DV can present with various injuries, whereof musculoskeletal presentation is common.ObjectivesThe DORIS study (Domestic violence...

Aberrant ecotropic viral integration site-1 (EVI-1) and myocyte enhancer factor 2C gene (MEF2C) in adult acute myeloid leukemia are associated with adverse t (9:22) & 11q23 rearrangements.

Acute myeloid leukemia (AML) shows multiple chromosomal translocations & point mutations which can be used to refine risk-adapted therapy in AML patients. Ecotropic viral integration site-1 (EVI-1) & myocyte enhancer factor 2C gene (MEF2C) are key regulatory transcription factors in hematopoiesis and leukemogenesis & both drive immune escape. This prospective study involved 80 adult de novo AML patients recruited from Oncology Center, Mansoura University, between March 2019 and July 2021. The MEF2C and EVI1 expression were measured using a Taqman probe-based qPCR assay. The results revealed that EVI1 and MEF2C expression were significantly elevated in AML patients as compared to control subjects (p = 0.001. 0.007 respectively). Aberrant expressions of EVI1 and MEF2C showed a significant negative correlation with hemoglobin levels (p = 0.034, 0.025 respectively), & bone marrow blasts (p = 0.007, 0.002 respectively). 11q23 translocation was significantly associated with EVI1 and MEF2C (p = 0.004 and 0.02 respectively). Also, t (9;22) was significantly associated with EVI1 and MEF2C (p = 0.01 and 0.03 respectively), higher expression of EVI1 and MEF2C were significantly associated with inferior outcome after induction therapy (p = 0.001 and 0.018 respectively) and shorter overall survival (p = 0.001, 0.014 respectively). In conclusion, EVI1 & MEF2C were significantly expressed in AML cases. EVI1 & MEF2C overexpression were significantly associated with 11q23 rearrangements and t (9;22) and were indicators for poor outcome in adult AML patients; These results could be a step towards personalized therapy in those patients.

Evaluation of urea breath test as a diagnostic tool for Helicobacter pylori infection in adult dyspeptic patients

In this editorial, we discuss the article in the World Journal of Gastroenterology . The article conducts a meta-analysis of the diagnostic accuracy of the urea breath test (UBT), a non-invasive method for detecting Helicobacter pylori (H. pylori) infection in humans. It is based on radionuclide-labeled urea. Various methods, both invasive and non-invasive, are available for diagnosing H. pylori infection, including endoscopy with biopsy, serology for immunoglobulin titers, stool antigen analysis, and UBT. Several guidelines recommend UBTs as the primary choice for diagnosing H. pylori infection and for reexamining after eradication therapy. It is used to be the first choice non-invasive test due to their high accuracy, specificity, rapid results, and simplicity. Moreover, its performance remains unaffected by the distribution of H. pylori in the stomach, allowing a high flow of patients to be tested. Despite its widespread use, the performance characteristics of UBT have been inconsistently described and remain incompletely defined. There are two UBTs available with Food and Drug Administration approval: The 13C and 14C tests. Both tests are affordable and can provide real-time results. Physicians may prefer the 13C test because it is non-radioactive, compared to 14C which uses a radioactive isotope, especially in young children and pregnant women. Although there was heterogeneity among the studies regarding the diagnostic accuracy of both UBTs, 13C-UBT consistently outperforms the 14C-UBT. This makes the 13C-UBT the preferred diagnostic approach. Furthermore, the provided findings of the meta-analysis emphasize the significance of precise considerations when choosing urea dosage, assessment timing, and measurement techniques for both the 13C-UBT and 14C-UBT, to enhance diagnostic precision.

Two Weeks Versus One Week of Maximal Patient-Intensivist Continuity for Adult Medical Intensive Care Patients: A Two-Center Target Trial Emulation.

To compare outcomes for 2 weeks vs. 1 week of maximal patient-intensivist continuity in the ICU. Retrospective cohort study. Two U.S. urban, teaching, medical ICUs where intensivists were scheduled for 2-week service blocks: site A was in the Midwest and site B was in the Northeast. Patients 18 years old or older admitted to a study ICU between March 1, 2017, and February 28, 2020. None. We applied target trial emulation to compare admission during an intensivist's first week (as a proxy for 2 wk of maximal continuity) vs. admission during their second week (as a proxy for 1 wk of maximal continuity). Outcomes included hospital mortality, ICU length of stay, and, for mechanically ventilated patients, duration of ventilation. Exploratory outcomes included imaging, echocardiogram, and consultation orders. We used inverse probability weighting to adjust for baseline differences and random-effects meta-analysis to calculate overall effect estimates. Among 2571 patients, 1254 were admitted during an intensivist's first week and 1317 were admitted during a second week. At sites A and B, hospital mortality rates were 25.8% and 24.2%, median ICU length of stay were 4 and 2 days, and median mechanical ventilation durations were 3 and 3 days, respectively. There were no differences in adjusted mortality (odds ratio [OR], 1.01 [95% CI, 0.96-1.06]) or ICU length of stay (-0.25 d [-0.82 d to +0.32 d]) for 2 weeks vs. 1 week of maximal continuity. Among mechanically ventilated patients, there were no differences in adjusted mortality (OR, 1.00 [0.87-1.16]), ICU length of stay (+0.06 d [-0.78 d to +0.91 d]), or duration of mechanical ventilation (+0.37 d [-0.46 d to +1.21 d]) for 2 weeks vs. 1 week of maximal continuity. Two weeks of maximal patient-intensivist continuity was not associated with differences in clinical outcomes compared with 1 week in two medical ICUs.

Evaluating site-of-care-related racial disparities in kidney graft failure using a novel federated learning framework.

Racial disparities in kidney transplant access and posttransplant outcomes exist between non-Hispanic Black (NHB) and non-Hispanic White (NHW) patients in the United States, with the site of care being a key contributor. Using multi-site data to examine the effect of site of care on racial disparities, the key challenge is the dilemma in sharing patient-level data due to regulations for protecting patients' privacy. We developed a federated learning framework, named dGEM-disparity (decentralized algorithm for Generalized linear mixed Effect Model for disparity quantification). Consisting of 2 modules, dGEM-disparity first provides accurately estimated common effects and calibrated hospital-specific effects by requiring only aggregated data from each center and then adopts a counterfactual modeling approach to assess whether the graft failure rates differ if NHB patients had been admitted at transplant centers in the same distribution as NHW patients were admitted. Utilizing United States Renal Data System data from 39043 adult patients across 73 transplant centers over 10 years, we found that if NHB patients had followed the distribution of NHW patients in admissions, there would be 38 fewer deaths or graft failures per 10000 NHB patients (95% CI, 35-40) within 1year of receiving a kidney transplant on average. The proposed framework facilitates efficient collaborations in clinical research networks. Additionally, the framework, by using counterfactual modeling to calculate the event rate, allows us to investigate contributions to racial disparities that may occur at the level of site of care. Our framework is broadly applicable to other decentralized datasets and disparities research related to differential access to care. Ultimately, our proposed framework will advance equity in human health by identifying and addressing hospital-level racial disparities.

Cost-effectiveness analysis of mosunetuzumab for treatment of relapsed or refractory follicular lymphoma after two or more lines of systemic therapy in the United States.

Mosunetuzumab has received accelerated approval by the US Food and Drug Administration for adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy. We evaluated the cost-effectiveness of mosunetuzumab for the treatment of R/R FL from a US private payer perspective. A partitioned survival model simulated lifetime costs and outcomes of mosunetuzumab against seven comparators: axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), tazemetostat (taz, EZH2 wild-type only), rituximab plus lenalidomide (R-Len) or bendamustine (R-Benda), obinutuzumab plus bendamustine (O-Benda), and a retrospective real-world cohort (RW) based on current patterns of care derived from US electronic health records (Flatiron Health). Efficacy data for mosunetuzumab were from the pivotal Phase II GO29781 trial (NCT02500407). Relative treatment efficacy was estimated from indirect treatment comparisons (ITCs). Costs included were related to treatment, adverse events, routine care, and terminal care. Except for drug costs (March 2023), all costs were inflated to 2022 US dollars. Costs and quality-adjusted life-years (QALYs) were used to calculate incremental cost-effectiveness ratios (ICERs). Net monetary benefit (NMB) was calculated using a willingness-to-pay (WTP) threshold of $150,000/QALY. Mosunetuzumab dominated taz, tisa-cel, and axi-cel with greater QALYs and lower costs. Mosunetuzumab was projected to be cost-effective against R-Benda, O-Benda, and RW with ICERs of $78,607, $42,731, and $21,434, respectively. Mosunetuzumab incurred lower costs but lower QALYs vs. R-Len. NMBs showed that mosunetuzumab was cost-effective against comparators except R-Len. Without head-to-head comparative data, the model had to rely on ITCs, some of which were affected by residual bias. Model inputs were obtained from multiple sources. Extensive sensitivity analyses assessed the importance of these uncertainties. Mosunetuzumab is estimated to be cost-effective compared with approved regimens except R-Len for the treatment of adults with R/R FL.

Genetic Predisposition to Sarcoma: What Should Clinicians Know?

Pathogenic germline variants in the setting of several associated cancer predisposition syndromes (CPS) may lead to the development of sarcoma. We would consider testing for a CPS in patients with a strong family history of cancer, multiple primary malignancies, and/or pediatric/adolescent/young adult patients diagnosed with other malignancies strongly associated with CPS. When a CPS is diagnosed in a patient with sarcoma, additional treatment considerations and imaging options for those patients are required. This applies particularly to the use of radiation therapy, ionizing radiation with diagnostic imaging, and the use of alkylating chemotherapy. As data and guidelines are currently lacking for many of these scenarios, we have adopted a shared decision-making process with patients and their families. If the best chance for cure in a patient with CPS requires utilization of radiation therapy or alkylating chemotherapy, we discuss the risks with the patient but do not omit these modalities. However, if there are treatment options that yield equivalent survival rates, yet avoid these modalities, we elect for those options. Considering staging imaging and post-therapy evaluation for sarcoma recurrence, we avoid surveillance techniques that utilize ionizing radiation when possible but do not completely omit them when their use is indicated.

Prospective validation of the Global Leadership Initiative on Malnutrition criteria for identifying malnutrition in hospitals: A protocol and feasibility pilot study.

The aim of this study was to pilot a protocol for prospective validation of the Global Leadership Initiative on Malnutrition (GLIM) criteria in hospital patients and evaluate its feasibility and patient acceptability. The validation protocol follows the GLIM consortium's rigorous methodological guidance. Protocol feasibility was assessed against criteria on recruitment (≥50%) and data collection completion (≥80%); protocol acceptability was assessed via patient satisfaction surveys and interviews. Adult inpatients in a tertiary hospital underwent four nutrition assessments (each by a different assessor); two Subjective Global Assessments (SGAs) and two GLIM assessments. All five GLIM criteria were assessed with bioelectrical impedance analysis used for muscle mass. Interrater reliability, criterion validity, and predictive validity were reported to detect trends. All primary feasibility criteria were met (consent rate 76%; data for GLIM criterion validity collected on 83% participants). Of predictive outcome data, 100% of hospital-related data, 82% of 6-month mortality data, and 39% of 6-month health-related quality of life data were collected. The mean (SD) age of participants was 61.0 ± 16.2 years, and 51.5% were male. The median (interquartile range) length of stay and body mass index were 7 (4-15) days and 25.6 (24.2-33.0) kg/m2, respectively. GLIM criteria diagnosed 70% of the patients as malnourished vs 55% with SGA. Most patients found the data collection acceptable with minimal burden. The methods outlined in this rigorous GLIM validation protocol are feasible to undertake in hospitals and acceptable to patients. This paper provides practical methodological guidance for future prospective GLIM validation studies.

Hemorrhage and thrombosis in COVID-19-patients supported with extracorporeal membrane oxygenation: an international study based on the COVID-19 critical care consortium

BackgroundExtracorporeal membrane oxygenation (ECMO) is a rescue therapy in patients with severe acute respiratory distress syndrome (ARDS) secondary to COVID-19. While bleeding and thrombosis complicate ECMO, these events may also occur secondary to COVID-19. Data regarding bleeding and thrombotic events in COVID-19 patients on ECMO are sparse.MethodsUsing the COVID-19 Critical Care Consortium database, we conducted a retrospective analysis on adult patients with severe COVID-19 requiring ECMO, including centers globally from 01/2020 to 06/2022, to determine the risk of ICU mortality associated with the occurrence of bleeding and clotting disorders.ResultsAmong 1,248 COVID-19 patients receiving ECMO support in the registry, coagulation complications were reported in 469 cases (38%), among whom 252 (54%) experienced hemorrhagic complications, 165 (35%) thrombotic complications, and 52 (11%) both. The hazard ratio (HR) for Intensive Care Unit mortality was higher in those with hemorrhagic-only complications than those with neither complication (adjusted HR = 1.60, 95% CI 1.28–1.99, p < 0.001). Death was reported in 617 of the 1248 (49.4%) with multiorgan failure (n = 257 of 617 [42%]), followed by respiratory failure (n = 130 of 617 [21%]) and septic shock [n = 55 of 617 (8.9%)] the leading causes.ConclusionsCoagulation disorders are frequent in COVID-19 ARDS patients receiving ECMO. Bleeding events contribute substantially to mortality in this cohort. However, this risk may be lower than previously reported in single-nation studies or early case reports.Trial registration ACTRN12620000421932 (https://covid19.cochrane.org/studies/crs-13513201).

Ghrelin for Neuroprotection in Post-Cardiac Arrest Coma: A Randomized Clinical Trial.

Out-of-hospital cardiac arrest survival rates have markedly risen in the last decades, but neurological outcome only improved marginally. Despite research on more than 20 neuroprotective strategies involving patients in comas after cardiac arrest, none have demonstrated unequivocal evidence of efficacy; however, treatment with acyl-ghrelin has shown improved functional and histological brain recovery in experimental models of cardiac arrest and was safe in a wide variety of human study populations. To determine safety and potential efficacy of intravenous acyl-ghrelin to improve neurological outcome in patients in a coma after cardiac arrest. A phase 2, double-blind, placebo-controlled, multicenter, randomized clinical trial, Ghrelin Treatment of Comatose Patients After Cardiac Arrest: A Clinical Trial to Promote Cerebral Recovery (GRECO), was conducted between January 18, 2019, and October 17, 2022. Adult patients 18 years or older who were in a comatose state after cardiac arrest were assessed for eligibility; patients were from 3 intensive care units in the Netherlands. Expected death within 48 hours or unfeasibility of treatment initiation within 12 hours were exclusion criteria. Patients were randomized to receive intravenous acyl-ghrelin, 600 μg (intervention group), or placebo (control group) within 12 hours after cardiac arrest, continued for 7 days, twice daily, in addition to standard care. Primary outcome was the score on the Cerebral Performance Categories (CPC) scale at 6 months. Safety outcomes included any serious adverse events. Secondary outcomes were mortality and neuron-specific enolase (NSE) levels on days 1 and 3. A total of 783 adult patients in a coma after cardiac arrest were assessed for eligibility, and 160 patients (median [IQR] age, 68 [57-75] years; 120 male [75%]) were enrolled. A total of 81 patients (51%) were assigned to the intervention group, and 79 (49%) were assigned to the control group. The common odds ratio (OR) for any CPC improvement in the intervention group was 1.78 (95% CI, 0.98-3.22; P = .06). This was consistent over all CPC categories. Mean (SD) NSE levels on day 1 after cardiac arrest were significantly lower in the intervention group (34 [6] μg/L vs 56 [13] μg/L; P = .04) and on day 3 (28 [6] μg/L vs 52 [14] μg/L; P = .08). Serious adverse events were comparable in incidence and type between the groups. Mortality was 37% (30 of 81) in the intervention group vs 51% (40 of 79) in the control group (absolute risk reduction, 14%; 95% CI, -2% to 29%; P = .08). In patients in a coma after cardiac arrest, intravenous treatment with acyl-ghrelin was safe and potentially effective to improve neurological outcome. Phase 3 trials are needed for conclusive evidence. Clinicaltrialsregister.eu: EUCTR2018-000005-23-NL.

Influence of elevated liver enzyme level on 30-day mortality rates in patients undergoing nonemergency orthopedic surgery

BackgroundThe effect of elevated preoperative liver enzyme levels on postoperative outcomes is a topic of concern to clinicians. This study explored the association between elevated preoperative liver enzyme levels and surgical outcomes in patients undergoing orthopedic surgery.MethodsUsing the American College of Surgeons National Surgical Quality Improvement Program database, we obtained data on adult patients who received nonemergency orthopedic surgery under general anesthesia between 2011 and 2021.ResultsWe evaluated the data of 477,524 patients, of whom 6.1% (24 197 patients) had elevated preoperative serum glutamic oxaloacetic transaminase (SGOT) levels. An elevated SGOT level was significantly associated with 30-day postoperative mortality (adjusted hazard ratio, 1.62; 95% confidence interval, 1.39 to 1.90). We determined that the mortality rate rose with SGOT levels. The results remained unchanged after propensity score matching.ConclusionElevated preoperative SGOT levels constitute an independent risk factor for 30-day postoperative mortality and are proportionately associated with the risk of 30-day postoperative mortality.

Metastatic germ cell tumors in serous cavities and cerebrospinal fluid: A single-center experience.

Metastatic germ cell tumors (GCTs) involving body cavity effusions and cerebrospinal fluid (CSF) are rare. Diagnosis is challenging because of limited morphological and clinicopathological information in the literature. A database search of our institution from 1990 to 2024 identified 27 cases of metastatic GCTs, comprising five pediatric and 22 adolescent and adult patients, in serous cavities or the CSF, including peritoneal (15), pleural (nine), CSF (two), and pericardial (one) fluid. The most common primary site was the testis (n=10), followed by the ovaries (n=7), mediastinum (n=4), retroperitoneum (n=3), pineal gland (n=2), and sacrum/coccyx (n=1). The primary tumors in 14 patients were mixed GCTs (six with a seminoma component), followed by immature teratomas (six), yolk sac tumors (three), embryonal carcinomas (two), pure seminomas (one), and postpubertal teratomas (one). The median interval between primary tumor diagnosis and diagnosis of fluid positivity was 7 months (range: 0-134 months). In nine cases, the malignant fluid was diagnosed simultaneously with or within 1 month of the primary tumor. GCT subtyping was performed on 23 of the 27 cytological specimens. Twenty-four patients (89%) also had metastases to other sites. Thirteen patients died of the disease (48%), with a median survival time of 4 months. Metastatic GCTs in serous effusions and CSF are often associated with disseminated disease and poor prognosis. Subtyping can be performed by cytomorphology combined with immunohistochemistry.

Pentoxifylline as a Novel Add-on Therapy for Major Depressive Disorder in Adult Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

Evidence indicates an association between immune dysregulation and major depressive disorder (MDD). Pentoxifylline (PTX), a phosphodiesterase inhibitor, has been shown to reduce pro-inflammatory activities. The aim of this study was to evaluate changes in depressive symptoms and pro-inflammatory markers after administration of PTX as an adjunctive agent to citalopram in patients with MDD. One hundred patients were randomly assigned to either citalopram (20 mg/day) plus placebo (twice daily) (n=50) or citalopram (20 mg/day) plus PTX (400 mg) (twice daily) (n=50). The Hamilton Depression Rating Scale-17 (HAM-D-17) scores at baseline, weeks 2, 4, 6, 8, 10, and 12 and serum levels of interleukin1-β (IL-1-β), tumor necrosis factor-α, C-reactive protein, IL-6, serotonin, IL-10, and brain-derived neurotrophic factor (BDNF) at baseline and week 12 were evaluated. HAM-D-17 score in the PTX group significantly reduced in comparison to the control group after weeks 4, 6, 8,10, and 12 ((LSMD): - 2.193, p=0.021; - 2.597, p=0.036; - 2.916, p=0.019; - 4.336, p=0.005; and - 4.087, p=0.008, respectively). Patients who received PTX had a better response (83%) and remission rate (79%) compared to the placebo group (49% and 40%, p=0.006 and p=0.01, respectively). Moreover, the reduction in serum concentrations of pro-inflammatory factors and increase in serotonin and BDNF in the PTX group was significantly greater than in the placebo group (p<0.001). These findings support the safety and efficacy of PTX as an adjunctive antidepressant agent with anti-inflammatory effects in patients with MDD.

Adherence and Persistence Among Risdiplam-Treated Individuals with Spinal Muscular Atrophy: A Retrospective Claims Analysis.

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletions and/or mutations in the survival of motor neuron1 (SMN1) gene. Risdiplam, the first and only oral SMN2 pre-mRNA splicing modifier, is US Food and Drug Administration-approved for the treatment of pediatric and adult patients with SMA. For patients with SMA, long-term adherence to and persistence with an SMA treatment may be important for achieving maximum clinical benefits. However, real-world evidence on patient adherence to and persistence with risdiplam is limited. This retrospective study examined real-worldadherence and persistence with risdiplamfrom a specialty pharmacy in patients with SMA over a 12-month period. Adherence was estimated by using proportion of days covered (PDC) and was calculated over variable (time between first and last fill) and fixed (time from first fill to study period end) intervals. Persistence was defined as no gap in supply ≥ 90days. Patients were included if the time between the index date and study observation period was ≥ 12months, if they initiated risdiplam between August 2020 and September 2022, received ≥ 2 risdiplam fills, and had an SMA diagnosis associated with a risdiplam fill. Subgroup analyses of risdiplam adherence and persistence were performed by age and primary payer type. The proportion of patients (N = 1636) adherent at 12months based on variable and fixed interval PDC was 93% and 79%, respectively. Adherence was high among patients on commercial insurance, Medicaid, or Medicare (range 86-96%). Mean persistence was 330.4days. The highest proportion of patients who were persistent were on Medicaid (81%). These findings demonstrate that patient adherence to and persistence with risdiplam treatment were high, including across all subgroups tested.

Heterogeneity of cognitive impairments in myotonic dystrophy type 1 explained by three distinct cognitive profiles.

Severity and nature of cognitive impairments in Myotonic dystrophy type 1 (DM1) are heterogeneous among studies. We hypothesized that this heterogeneity is explained by different cognitive profiles in DM1, with different clinical, biological and behavioral features. Adult patients with genetically proven DM1 underwent a clinical, neuropsychological and behavioral assessment. We conducted a k-means clustering analysis on 9 cognitive tests representative of different domains (verbal/non-verbal episodic memory, visuo-constructive abilities, visual gnosis, executive functions, information processing speed). We included 124 DM1 patients. Mean age was 45.1 ± 13.5years [19.8-73.2], mean age of onset was 30.4 ± 15.7years [5-72], and mean CTG triplets' expansion size was 489.7 ± 351.8 [50-1600]. We found 3 cognitive clusters, including, respectively, 84, 29 and 11 patients. The first cluster included patients with more preserved cognitive functions; the second included patients with worse cognitive performances which predominate on executive functions; and the third even more pronounced and diffuse cognitive deficits. Younger patients, with a more recent DM1 clinical onset, higher educational level were more frequently classified in the cluster with more preserved cognitive functions. There were no significant differences between clusters regarding CTG triplets' expansion, neither age at DM1 onset, nor most of behavioral measures. We found different cognitive profiles in our DM1 population, which seem influenced by age and DM1 duration. Our findings may explain the heterogeneity of studies about cognition in DM1, and suggest a potential neurodegenerative mechanism in DM1 adults.

Prognostic Assessment of Histopathologic Lesions in Patients with Community-Acquired Acute Kidney Injury with Biopsy-Proven Acute Tubular Necrosis.

Community-acquired acute kidney injury (CA-AKI) was more likely to be comorbid with underlying kidney histopathological lesions in addition to acute tubular necrosis (ATN). Thus, we tried to clarify the histological determinants that could influence the prognosis and recovery of CA-AKI patients with biopsy-proven ATN. Adult patients with CA-AKI with biopsy-proven ATN who underwent renal biopsy at Shanghai Changzheng Hospital from January 1, 2010, to December 31, 2018, were included and followed up for 5 years. The impacts of histopathological lesions on short-term and long-term renal dysfunction were also analysed. Multivariate analysis revealed that ATNs, crescents, and decrease of arteriole lumens increased short-term dialysis requirements. The severity of ATN was closely associated with renal survival. According to the Kaplan-Meier analysis, the severity of ATN was significantly associated with short-term dialysis needs and long-term development of end-stage kidney disease (ESKD) during follow-up. Crescent and decrease of arteriole lumens are significantly associated with progression to ESKD and exert synergistic effects with ATN. For patients who did not progress to dialysis, tubular atrophic/interstitial fibrosis and endocapillary lesions were more relevant to partial recovery of renal function after CA-AKI at the three-month follow-up and increased the risk of chronic kidney disease (CKD) stage 3-5 at the five-year follow-up. According to our correlation analysis, endocapillary lesions and crescents were positively correlated with ATN. Histopathologic lesions, apart from tubular necrosis, contributed to the detrimental short-term and long-term renal prognosis of CA-AKI patients with ATN; concomitant histopathologic lesions exerted a combined impact on renal survival together with ATN in CA-AKI patients.

Combination immunotherapy with vaccine and oncolytic HSV virotherapy is time dependent.

Oncolytic virotherapy or immunovirotherapy is a strategy that utilizes viruses to selectively infect and kill tumor cells while also stimulating an immune response against the tumor. Early clinical trials in both pediatric and adult patients using oncolytic herpes simplex viruses (oHSVs) have demonstrated safety and promising efficacy; however, combinatorial strategies designed to enhance oncolysis while also promoting durable T cell responses for sustaining disease remission are likely required. We hypothesized that combining the direct tumor cell killing and innate immune stimulation by oHSV with a vaccine that promotes T cell mediated immunity may lead to more durable tumor regression. To this end, we investigated the preclinical efficacy and potential synergy of combining oHSV with a self-assembling nanoparticle vaccine co-delivering peptide antigens and Toll-like receptor-7 and -8 agonists (TLR-7/8a) (referred to as SNAPvax™), that induces robust tumor specific T cell immunity. We then assessed how timing of the treatments (i.e., vaccine before or after oHSV) impacts T cell responses, viral replication, and preclinical efficacy. The sequence of treatments was critical, as survival was significantly enhanced when the SNAPvax™ vaccine was given prior to oHSV. Increased clinical efficacy was associated with reduced tumour volume and increases in virus replication and tumor antigen specific CD8+ T cells. These findings substantiate the criticality of combination immunotherapy timing and provide preclinical support for combining SNAPvax with oHSV as a promising treatment approach for both pediatric and adult tumors.

Refraining from closed reduction of displaced distal radius fractures in the emergency department—in short: the RECORDED trial

BackgroundWith roughly 45,000 adult patients each year, distal radius fractures are one of the most common fractures in the emergency department. Approximately 60% of all these fractures are displaced and require surgery. The current guidelines advise to perform closed reduction of these fractures awaiting surgery, as it may lead to post-reduction pain relief and release tension of the surrounding neurovascular structures. Recent studies have shown that successful reduction does not warrant conservative treatment, while patients find it painful or even traumatizing. The aim of this study is to determine whether closed reduction can be safely abandoned in these patients.MethodsIn this multicenter randomized clinical trial, we will randomize between closed reduction followed by plaster casting and only plaster casting. Patients aged 18 to 75 years, presenting at the emergency department with a displaced distal radial fracture and requiring surgery according to the attending surgeon, are eligible for inclusion. Primary outcome is pain assessed with daily VAS scores from the visit to the emergency department until surgery. Secondary outcomes are function assessed by PRWHE, length of stay at the emergency department, length of surgery, return to work, patient satisfaction, and complications. A total of 134 patients will be included in this study with follow-up of 1 year.DiscussionIf our study shows that patients who did not receive closed reduction experience no significant drawbacks, we might be able to reorganize the initial care for distal radial fractures in the emergency department. If surgery is warranted, the patient can be sent home with a plaster cast to await the call for admission, decreasing the time spend in the emergency room drastically.Trial registrationThis trial was registered on January 27, 2023.

Levels of anti-topoisomerase I antibody correlated with short onset of cardiopulmonary involvement in Thai systemic sclerosis patients

Anti-topoisomerase-I antibody (ATA) is associated with disease severity and internal organ involvement in patients with systemic sclerosis (SSc). The correlation between ATA levels and the clinical course of SSc is unclear. We aimed to determine the correlation between ATA level and survival time and the onset of internal organ fibrosis in SSc patients. This historical cohort study was conducted in adult SSc patients with quantitative tests of ATA between January 2019 and December 2022. Patients with overlap syndrome and no quantitative ATA test were excluded. According to the sample size calculation, and 10% compensated for missing data, a total of 153 patients were needed. The respective mean age on the study date and median ATA level was 59.9 ± 11.3 years and 370 U/mL (range 195–652). Most cases (107 cases; 69.9%) were the diffuse cutaneous SSc subset. According to a multivariable analysis, the ATA titer had a negative correlation with the onset of cardiac involvement (Rho − 0.47, p = 0.01), and had a positive correlation with skin thickness progression (Rho 0.39, p = 0.04). Eleven cases exhibited ATA levels < 7 U/mL and outlier ATA levels were excluded, 142 cases were included in the sensitivity analysis, and multivariable analysis showed the correlation between early onset of ILD and cardiac involvement (Rho − 0.43, p = 0.03 and Rho − 0.51, p = 0.01, respectively). The ATA level was correlated with neither the survival time nor the onset of renal crisis in both analyses. High ATA levels were correlated with a short onset of ILD and cardiac involvement and the presence of extensive skin tightness. Quantitative tests of ATA could serve as an effective tool for identifying patients at risk of an unfavorable prognosis.