Multicenter Study Research Articles

A CT-based subregional radiomics nomogram for predicting local recurrence-free survival in esophageal squamous cell cancer patients treated by definitive chemoradiotherapy: a multicenter study

BackgroundTo develop and validate an online individualized model for predicting local recurrence-free survival (LRFS) in esophageal squamous cell carcinoma (ESCC) treated by definitive chemoradiotherapy (dCRT).MethodsESCC patients from three hospitals were randomly stratified into the training set (715) and the internal testing set (179), and patients from the other hospital as the external testing set (120). The important radiomic features extracted from contrast-enhanced computed tomography (CECT)-based subregions clustered from the whole volume of tumor and peritumor were selected and used to construct the subregion-based radiomic signature by using COX proportional hazards model, which was compared with the tumor-based radiomic signature. The clinical model and the radiomics model combing the clinical factors and the radiomic signature were further constructed and compared, which were validated in two testing sets.ResultsThe subresion-based radiomic signature showed better prognostic performance than the tumor-based radiomic signature (training: 0.642 vs. 0.621, internal testing: 0.657 vs. 0.638, external testing: 0.636 vs. 0.612). Although the tumor-based radiomic signature, the subregion-based radiomic signature, the tumor-based radiomics model, and the subregion-based radiomics model had better performance compared to the clinical model, only the subregion-based radiomics model showed a significant advantage (p < 0.05; training: 0.666 vs. 0.616, internal testing: 0.689 vs. 0.649, external testing: 0.642 vs. 0.604). The clinical model and the subregion-based radiomics model were visualized as the nomograms, which are available online and could interactively calculate LRFS probability.ConclusionsWe established and validated a CECT-based online radiomics nomogram for predicting LRFS in ESCC received dCRT, which outperformed the clinical model and might serve as a powerful tool to facilitate individualized treatment.Trial registrationThis retrospective study was approved by the ethics committee (KY20222145-C-1).

Evaluation of clinical outcomes and risk factors associated with mortality in patients with Stenotrophomonas maltophilia bloodstream infection: a multicenter study

BackgroundStenotrophomonas maltophilia, a pathogen that colonizes medical equipment and causes nosocomial infections due to its ability to form biofilms, has high mortality rates. This study investigated the risk factors related to mortality in patients who were diagnosed with S. maltophilia bacteremia.MethodsIt is a multi-center, retrospective ad observational cohort study. The demographic characteristics, clinical findings, microbiological data, and risk factors for patients were obtained from the medical records of patients at ten different hospitals between January 1, 2018, and June 30, 2023.ResultsThe study included a total of 321 patients. The observed thirty-day mortality rate was 46.1%. A central venous catheter (CVC) was present in 276 patients (86%), and in 66 of these patients (23.9%) the CVC was removed. While only 18 patients (5.6%) received appropriate empirical antibiotics, 242 (75.4%) patients received appropriate antibiotics according to antimicrobial susceptibility test (AST) results and treatment revisions. Multivariate analysis revealed that advanced age (hazard ratio [HR] = 1.02; 95% confidence interval [CI]: 1.00– 1.03), appropriate antibiotic treatment (HR = 0.35; 95% CI: 0.23–0.52), and removal of central venous catheters (HR = 0.31; 95% CI: 0.16–0.60) were significantly related to reduced mortality.ConclusionsS. maltophilia is a significant pathogen, and to reduce its high mortality rate, removal of the CVC and switching to appropriate antibiotics should be performed as soon as possible.

Point-of-care testing improves care timeliness in the emergency department. A multicenter randomized clinical trial (study POCTUR).

Emergency department (ED) crowding is a widespread problem that positions patients at risk. The desire to improve the ED throughput requires novel approaches. Point-of-care testing (POCT) has emerged as useful technology that could contribute to create more efficient patient flow and better timeliness in the ED. The main objective of our study is to demonstrate, in a multicenter study, that POCT benefits care timeliness in the ED. We conducted a multicenter and cluster randomized study. A total of 3,200 patients. We randomly assigned patients to a POCT group or Central Laboratory Group. The primary outcome was the ED time to clinical decision. The secondary outcome included the length of stay and the laboratory turnaround time. Readmission within the seven after discharge was also calculated. The primary finding of this study is a strategy based on POCT that aims to significantly improve care timeliness in the ED. We found significant reductions in all outcomes regardless of presentation reason, patient disposition or hospital type. Time to clinical decision decreased by 75.2 min (205-129.8), length of stay by 77.5 min (273.1-195.6) and laboratory turnaround time by 56.2 min (82.2-26) in the POCT group. No increase in readmission was found. Our strategy represents a good approach to optimize timeliness in the ED. It should be seen as a starting point for further operational research focusing on POCT for improving throughput and reducing crowding in the ED.

Active listening modulates the spatial hearing experience: a multicentric study.

Although flexible and portable virtual reality technologies have simplified measuring participants' perception of acoustic space, their clinical adoption remains limited, often lacking ecological fidelity. In clinical practice, participants are typically instructed to remain still when testing sound localization, whereas head movements are crucial in daily life. Additionally, assessing spatial hearing extends beyond measuring accuracy to include meta-cognitive evaluations like perceived effort and confidence, which are rarely adopted. Our study hypothesized that allowing head movement during sound localization, compared to a static head condition, would reduce perceived listening effort and enhance confidence in normal hearing participants. Conducted across three audiology and otology hospital services in Northern Italy, the study involved personnel inexperienced with our VR equipment. This also tested the feasibility and usability of our VR approach in clinical settings. Results showed that head movements reduced subjective effort but did not significantly affect perceived confidence. However, during the active condition, participants reporting higher confidence exhibited less head movement and explored the space less. Similarly, those with less head movement reported lower listening effort. These findings underscore the importance of allowing natural posture to capture the full extent of spatial hearing capabilities and the value of including metacognitive evaluations in assessing performance. Our use of affordable, off-the-shelf VR equipment effectively measured spatial hearing in clinical settings, providing a flexible alternative to current static systems. This approach highlights the potential for more dynamic and comprehensive assessments in clinical audiology.

Clinical evaluation of AYUSH-SL in patients receiving mass drug administration for the treatment of chronic inflammatory lymphedema, a double blind, placebo controlled, multicentric study.

A 2.5-year placebo controlled double blind trial was conducted to investigate the safety and efficacy of AYUSH- SL, a poly- herbal Ayurvedic formulation on filarial lymphedema in different endemic areas of India. Lymphatic filariasis (LF) is caused by parasitic nematodes from Wuchereria bancrofti, Brugia malayi, or B. timori that are transmitted through mosquitoes. In Ayurveda, LF has been elaborately narrated under the heading Shlipada, and the literature also includes detailed therapeutic measures. The multicenter, prospective, parallel group interventional study of a total of 180 participants were recruited within the duration through competitive enrollment. Diagnosed cases of grade I and grade II filarial lymphedema of Grade I and Grade II (lower extremities) were included in the trial. The study group was treated with MDA and AYUSH-SL or its placebo tablet. The control group had received MDA and a matching placebo. The primary outcome measure was the reduction in edema calculated for analysis by percentage reduction from baseline at the 4th, 12th and 24th week. Secondary outcome measures included improved quality of life (QoL), which was assessed using the Lymphatic Filariasis Specific QoL Questionnaire, and prevention of recurrence of acute episodes, which was evaluated by investigating the presence and severity of episodes in the past 4 weeks. The water displacement method for the evaluation of the efficacy of the intervention was shown to be highly significant compared to the baseline value (right leg; 3071.60 ± 970.482, 2828.40±829.339, p<0.001and Left leg; 3158.69 ± 1136.391, 2890.73 ±1077.475, p<0.001). There was significant improvement of Quality of Life in the LF QoL Questionnaire (p <0.001) at each follow-up visit in both groups. Safety estimations on hematologic and biochemical parameters were within limits and or changes were not significant. The results revealed that AYUSH- SL is safe and effective for FL due to its comprehensive anti-inflammatory, antimicrobial, and anti-allergic activities.

Acute kidney injury associated with increased costs in the neonatal intensive care unit: analysis of Pediatric Health Information System database.

Compare neonatal intensive care unit hospitalization costs between neonates with and without AKI; identify predictors of AKI-associated costs. We hypothesized neonates with AKI would amass more costs than those without AKI. Retrospective, multicenter cohort study of surviving neonates cared for 2015-2021 in Pediatric Health Information System database. The primary outcome was estimated hospitalization costs. Data from 304,725 neonates were evaluated, 8774 (3%) with AKI and 295,951 (97%) without AKI. Neonates with AKI had $58,807 greater adjusted costs than those without AKI. AKI-associated costs were most strongly driven by Feudtner Pediatric Complex Chronic Conditions Classifications (cardiovascaular, congenital/genetic, gastrointestinal, medical technology) and gestational age. Adjusted costs decreased with increasing gestational age, regardless of AKI status. AKI is independently associated with increased hospital costs. Knowledge of these drivers can help in identifying high-value practices for cost mitigation strategies.

Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Human Papillomavirus–Related Oropharyngeal Cancer

Distant metastasis (DM) remains the leading cause of death in patients treated for human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). An effective treatment strategy needs to address DM while reducing treatment-related toxic effects. To assess DM-free survival in patients with HPV-OPSCC treated with neoadjuvant chemotherapy followed by transoral robotic surgery (NECTORS) and neck dissection compared with standard of care, concurrent chemoradiation (CCRT). This multicenter retrospective cohort study compares prospective data from the NECTORS treatment group with a historical cohort of patients treated with CCRT. Patients with American Joint Committee on Cancer seventh edition stage III and IVa HPV-OPSCC treated with NECTORS and CCRT between February 2010 and September 2021 were included. Data were analyzed in September 2024. Patients in the NECTORS arm were treated with 3 cycles of neoadjuvant docetaxel and cisplatin followed by TORS and neck dissection. Patients in the radiation therapy arm were treated with concurrent high-dose cisplatin and radiotherapy. DM-free survival was analyzed with Kaplan-Meier and Cox regression after adjusting for age, sex, tobacco and alcohol use, site, and cancer stage. Of 342 included patients, 282 (82.5%) were male, and the mean (SD) age was 61.4 (9.4) years. A total of 232 patients were treated with CCRT and 110 patients were treated with NECTORS. Within the CCRT arm, 11 patients (4.7%) had locoregional recurrence (LRR), 5 (2.2%) had LRR and DM, and 28 (12.1%) developed distant-only metastasis. For patients treated with NECTORS, 5 (4.5%) developed LRR, 1 (0.9%) developed LRR plus DM, and no patients developed distant-only metastasis. With pseudorandomization matching for T and N stages, 209 patients were matched between the 2 treatment groups for further analysis (105 in the CCRT treatment arm and 104 in the NECTORS arm). The median (range) follow-up period for the CCRT and NECTORS groups were 5.8 (3.8-7.5) years and 5.1 (4.0-5.9) years, respectively. The hazard ratio of developing distant recurrence in the CCRT group was 10.77 (95% CI, 1.40-82.90) in univariate analysis and 9.98 (95% CI, 1.29-77.29) in multivariable analysis. In Kaplan-Meier survival analysis, the risk of developing DM was higher in the CCRT group. The hazard ratio for failure anywhere in the CCRT group was 3.32 (95% CI, 1.23-8.97) in univariate analysis and 3.21 (95% CI, 1.18-8.72) in multivariable analysis. In this study, neoadjuvant chemotherapy followed by transoral robotic surgery and neck dissection was an effective treatment option for patients with stage III and IVa HPV-OPSCC. Findings from our study suggest lower rates of DM with NECTORS worthy of further investigation in prospective randomized trials.

First results of migoprotafib, a potent and highly selective Src homology-2 domain-containing phosphatase 2 (SHP2) inhibitor in patients with advanced solid tumors.

Src homology-2 domain-containing phosphatase 2 (SHP2) promotes RAS-MAPK signaling and tumorigenesis and is a promising therapeutic target for multiple solid tumors. Migoprotafib is a potent and highly selective SHP2 inhibitor designed for the treatment of RAS-MAPK driven cancers, particularly in combination with other targeted agents. Here we report first-in-human study results of single agent migoprotafib in advanced solid tumor patients. We conducted a phase 1a, open-label, multi-center, dose-escalation and expansion study in adult patients with locally advanced or metastatic solid tumors. The key objectives were to evaluate safety, pharmacokinetics, pharmacodynamics (peripheral blood pERK) and preliminary anti-tumor activity. Fifty-six heavily pre-treated patients were treated with migoprotafib (10-150 mg QD). Migoprotafib had a rapid absorption rate (~0.5-2 hours) with dose-dependent increases in exposure and pathway modulation (pERK changes). The maximum tolerated dose was 100 mg and the recommended phase 2 dose (RP2D) was 60 mg daily (QD) based on safety, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity. Migoprotafib was generally well tolerated with the most frequent adverse events of diarrhea, peripheral edema, dyspnea, anemia, constipation, fatigue, AST increase and platelet count decrease. Stable disease was observed in 10 patients (18%). Migoprotafib had predictable, dose-dependent PK with an effective half-life that supports QD dosing and demonstrated promising safety, tolerability, and clinical activity at the RP2D. Further clinical testing of migoprotafib in combination with other targeted agents is warranted.

Association of Clinical, Biomechanical, and Psychosocial Factors with Smile Dynamics in Unilateral Cleft Lip: A Multicenter Observational Study.

To investigate the association between clinical, biomechanical, and psychosocial factors and smiling behavior in individuals with treated unilateral cleft lip with or without cleft palate (UCL ± P) compared to non-cleft controls. Multicenter observational study in New Zealand. Individuals aged ≥15 (N = 42) comprised 2 study groups: a UCL ± P group (N = 21) and a non-cleft control group (N = 21). Participants viewed an amusing video while their facial expressions were recorded. Smile features were automatically detected via software. A clinical outcome, nasolabial esthetics, was scored using the Asher-McDade system. Perioral biomechanical properties were measured via myotonometry. Smile Esthetics-related Quality of Life (SERQoL), Orofacial Esthetics Scale (OES), and personality (IPIP-NEO-60) questionnaires were completed. Smile features and personality traits did not differ between the groups. Participants with UCL ± P exhibited higher stiffness (+44.2%; Cohen's d = 1.6) and tone (+22.6%; Cohen's d = 1.9) at the cleft scar site, and higher decrement (or lower elasticity, +8.5%; Cohen's d = 0.8) adjacent to the scar. Nasolabial esthetics and elasticity of the scar correlated with the duration of smiles and relative smile time (-0.50 < R < -0.44; p < .05). Participants in the UCL ± P group had lower scores for the OES and higher impacts on SERQoL for social contacts and dental self-confidence. Adolescents and adults with UCL ± P exhibit similar smile behavior as their cleft-free peers-at least in non-social settings. Nasolabial esthetics and perioral biomechanical properties are associated with propensity to smile. UCL ± P is negatively associated with smile-related quality of life and an individual's perception of their facial appearance.

Maternal oxygenation and fetal-neonatal mortality among patients with COVID-19 requiring advanced respiratory support in ICU: A multicenter prospective cohort study.

To explore the association of maternal characteristics, oxygenation, and mechanical ventilatory parameters with fetal and neonatal outcomes. The present study was a multicenter, binational (Argentina/Colombia), prospective, cohort study, conducted in 21 intensive care units (ICUs) and including pregnant or postpartum patients with COVID-19 pneumonia requiring advanced respiratory support and their fetuses/neonates. Advanced respiratory support was defined as high-flow nasal cannula (HFNC), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV). A total of 91 patients were admitted to 21 ICUs: 63 (69%) antepartum and 28 (31%) postpartum. Among those admitted antepartum (63), delivery was induced in 43 (68.3%), being the reasons mostly maternal (28/43; 65.1%). Of 71 births, 64 (90%) were preterm. A total of 14 fetal/neonatal losses (14/91;15.4%) occurred. The main differences between patients whose fetuses/neonates survived versus those who did not survive were in APACHE II (12 [7-15] vs. 16.5 [14-20]; P = 0.003), SOFA24 (4 [3-5] vs. 6.5 [5-8]; P = 0.001), gestational age at delivery (32.9 ± 3 vs. 27.6 ± 6.2; P = 0.014), acute respiratory distress syndrome (54 [70.1%] vs. 14 [100%]; P = 0.011), septic shock (26 [33.8%] vs. 9 [64.3%]; P = 0.031), IMV (55 [71.4%] vs. 14 [100%]; P = 0.019) and plateau pressure before delivery (23 [21-26] vs. 28 [27-30]; P = 0.019). The incidence of fetal/neonatal mortality among 47 pregnant patients requiring IMV with SpO2 < 95% versus SpO2 >95% before intubation was 12/35 (34.28%) versus 1/12 (8.33%), respectively; P = 0.163. The incidence of fetal/neonatal mortality among those with SpO2 <95% versus SpO2 >95% before delivery was 5/18 (27.77%) versus 8/29 (25.58%), respectively; P = 0.999. The vast majority of births were preterm. Among patients admitted antepartum, most deliveries were induced for maternal reasons. Fetal/neonatal losses were associated with gestational age at delivery, maternal severity of illness on admission and certain ventilatory parameters but not with maternal oxygenation, as is commonly the focus in these patients.

The relationship between continuation of exercise habit for three years and endothelial function in patients with hypertension.

The aim of this study was to evaluate the relationship between continuation of exercise habit for a long period and endothelial function assessed by flow-mediated vasodilation (FMD) in patients with hypertension. This study was a multicenter retrospective observational study. A total of 639 patients with hypertension were enrolled in this study. The subjects were divided into two groups based on information on exercise habit: a regular exercise group and a non-regular exercise group (control group). The regular exercise group was defined as patients who had an exercise habit during a 3-year follow-up period. There was no significant difference in FMD at baseline between the regular exercise group and control group. The change in FMD examined by the Wilcoxon signed rank test was significantly larger in the regular exercise group than in the control group (0.4 (-1.4, 2.0) % vs. -0.1 (-2.2, 1.4) %, p = 0.008). After adjustment for confounding factors for FMD, the odds ratio for increase in FMD was significantly larger in the regular exercise group than in the control groups. (OR: 1.59, 95% CI: 1.14-2.21, p = 0.006) A cubic spline curve revealed that even subjects with regular exercise who had a mean exercise intensity of less than 20 Mets・hour/week a had higher odds ratio for increase in endothelial function compared to the control group. These findings suggest that patients with hypertension who engage in regular exercise exhibited better endothelial function compared to those who do not exercise. Clinical Trial Registry Information: http://www.umin.ac.jp (UMIN000012951).

Impact of cerebral collateral recycle status on clinical outcomes in elderly patients with endovascular stroke treatment

BackgroundElderly patients are at high risk of acute ischemic stroke caused by large vessel occlusion (AIS-LVO) and usually suffer disability and fatality from stroke even after receiving endovascular treatment (EVT). Previous studies lacked the knowledge of comprehensive cerebral collateral for elderly patients. Hence, we explore the role of cerebral collateral recycle (CCR) status in clinical outcomes in a real-world setting among elderly AIS-LVO patients undergoing EVT. MethodsThis was a multicenter retrospective cohort study. Computed tomographic angiography (CTA) at admission was applied to evaluate cerebral venous outflow profiles by the Cortical Vein Opacification Score (COVES) and pial arterial collaterals by the Tan scale. According to the status of cerebral collaterals, enrolled patients were divided into the poor, moderate, and favorable CCR groups. The primary outcome was functional independence (90-day modified Rankin Scale score 0-2). ResultsAmong 860 AIS-LVO patients receiving EVT, a total of 338 elderly patients were included in the present study after strict screening. Compared with the poor CCR group, the moderate CCR group (31.1% vs. 10.2%; adjusted odds ratio[aOR] 3.80; 95% confidence interval[CI] 1.71-8.44; P=0.001) and the favorable CCR group (63.3% vs. 10.2%; aOR 8.49; 95% CI 4.02-17.92; P<0.001) both had a significantly higher rate of functional independence. In subgroup analysis, similar results were found in AIS-LVO patients with older age, large core infarction, or late time window. ConclusionThe cerebral collateral status in elderly patients with AIS-LVO treated by EVT is a strong predictor of functional outcomes and more robust CCR means better outcomes.

A web-based dynamic nomogram for estimating talaromycosis risk in hospitalized HIV-positive patients.

Our study aimed to develop and validate a nomogram to assess talaromycosis risk in hospitalized HIV-positive patients. Prediction models were built using data from a multicentre retrospective cohort study in China. On the basis of the inclusion and exclusion criteria, we collected data from 1564 hospitalized HIV-positive patients in four hospitals from 2010 to 2019. Inpatients were randomly assigned to the training or validation group at a 7:3 ratio. To identify the potential risk factors for talaromycosis in HIV-infected patients, univariate and multivariate logistic regression analyses were conducted. Through multivariate logistic regression, we determined ten variables that were independent risk factors for talaromycosis in HIV-infected individuals. A nomogram was developed following the findings of the multivariate logistic regression analysis. For user convenience, a web-based nomogram calculator was also created. The nomogram demonstrated excellent discrimination in both the training and validation groups [area under the ROC curve (AUC)=0.883 vs. 0.889] and good calibration. The results of the clinical impact curve (CIC) analysis and decision curve analysis (DCA) confirmed the clinical utility of the model. Clinicians will benefit from this simple, practical, and quantitative strategy to predict talaromycosis risk in HIV-infected patients and can implement appropriate interventions accordingly.

Clinical characteristics and diagnostic accuracy of preliminary diagnoses in adults with infections in Danish emergency departments: a multicentre combined cross-sectional and diagnostic study

ObjectiveRapid and accurate infection diagnosis is a prerequisite for appropriate antibiotic prescriptions in an ED. Accurately diagnosing acute infections can be difficult due to nonspecific symptoms and limitations of diagnostic...

Management and outcomes of pediatric optic neuritis in a tertiary hospital in Riyadh, Saudi Arabia: a retrospective study

BackgroundAlthough pediatric optic neuritis (PON) is a rare condition, current advancements in its diagnosis, investigation, and treatment suggest that a more precise risk assessment is necessary given the history of irreversible damage and functional degeneration of the optic nerve. Additionally, after further investigations and/or new neurological events, the initial diagnosis is revised.AimTo report clinical profile, management and outcome of different demyelinating disease phenotypes of pediatric optic neuritis (PON) in individuals under the age of 18 years in a tertiary center in the Kingdom of Saudi Arabia (KSA).Study methodWe analyzed the electronic medical records of pediatric patients under the age of 18 years who first experienced different phenotypes of demyelinating PON between January 2000 and December 2020 as part of this retrospective case series. We studied the clinical characteristics, serology, imaging data, treatment regimens, and follow-up of the patients. Descriptive statistics were calculated.ResultsThe majority of patients were less than 10 years old (63.6%), males (63.6%) and had bilateral involvement (72.7%). Among the 11 patients diagnosed with PON, 5(45.5%) had isolated pediatric optic neuritis, 1 (9.1%) had multiple sclerosis (MS), 1(9.1%) had neuromyelitis optica spectrum disorder (NMOSD), 1 (9.1%) had acute disseminated encephalomyelitis (ADEM) and 3 (27.2%) had myelin oligodendrocyte glycoprotein (MOG) antibody associated disease (MOGAD). Despite poor vision at presentation, most of the patients improved, 81.1% achieved a BCVA of ≥ 20/40, and 36.6% attained 20/20 visual acuity. Four patients experienced recurrence.ConclusionsThe overlapping features of disease phenotypes in PON make it difficult to identify the underlying cause. The findings of this retrospective case series suggest the need for a future prospective multicenter study for a better understanding of the different phenotypes.

Genetics of urinary bladder paragangliomas: a multi-center study of a Chinese cohort.

Pheochromocytomas and paragangliomas (PPGLs) exhibit the highest degree of heritability among all human tumors, yet the genetics of urinary bladder paragangliomas (UBPGLs) remains poorly understood. The present study aims to examine the characteristics of a cohort of Chinese patients with UBPGLs, focusing particularly on genetics. The study included 70 Chinese patients with UBPGLs from 15 centers in China, 240 patients with non-head and neck PGLs (non-HNPGLs) outside the urine bladder, and 16 Caucasian patients with UBPGLs. Tumor DNA samples were sequenced by next generation sequencing. All identified pathogenic variants (PVs) were confirmed by Sanger sequencing. Among the 70 Chinese patients, PVs were identified in 38 cases: 23 in cluster 1A (13 SDHB, 1 SDHD, 1 SDHA, 4 IDH1, 2 SLC25A11, and 2 FH), 4 in cluster 1B (3 EPAS1 and 1 EGLN1), and 11 in cluster 2 genes (7 HRAS, 1 FGFR1, 2 NF1, and 1 H3F3A). Compared with other non-HNPGLs, UBPGLs had more PVs in cluster 1A genes (32.9% vs. 14.2%, p < 0.001), but fewer in cluster 1B (5.7% vs. 19.2%, p = 0.002) and cluster 2 genes (15.7% vs. 42.5%, p < 0.001). PVs in SDHB (18.6%) was the most common in Chinese patients with UBPGLs, followed by HRAS (10.0%). No PVs was found in 45.7% of all UBPGLs. PVs in HRAS, SLC25A11, EPAS1, and FH were also identified in Caucasians with UBPGLs. Chinese patients with UBPGLs have a diverse genetic profile. PVs in cluster 1A genes underlie nearly 1/3 of patients, highlighting the importance of genetic testing. Diverse germline and somatic PVs are also present in Caucasian patients with UBPGLs.

The impact of Artificial Intelligence in detecting esophageal squamous cell carcinoma: advances and challenges

This review explores the transformative role of artificial intelligence (AI), especially through deep learning (DL) and convolutional neural networks (CNNs), in the early detection of esophageal squamous cell carcinoma (ESCC). ESCC presents significant diagnostic challenges due to its aggressive nature and high mortality, often diagnosed at advanced stages. Traditional endoscopic methods, while essential, suffer from limitations like interobserver variability, especially for subtle early lesions. AI-based systems have demonstrated high sensitivity in identifying these early neoplasms, reducing diagnostic discrepancies and enhancing precision. Through a bibliographic review, the article highlights recent AI advancements, particularly in utilizing CNNs to identify early-stage ESCC. These tools have shown the potential to improve diagnostic accuracy even among less experienced endoscopists and provide critical support in clinical decision-making, including biopsy guidance and lesion mapping in chromoendoscopy and narrow-band imaging (NBI). Despite promising results, challenges persist in AI’s practical application, such as the need for extensive data for training, clinical validation, and standardization across different endoscopic equipment. The study underscores the need for large-scale multicenter studies and standardization to solidify AI’s role in ESCC diagnosis. It envisions a future where AI not only serves as a diagnostic support tool but becomes integral to endoscopic practices, requiring continued technological development, ethical considerations, and regulatory frameworks to maximize clinical benefit.

Trends and Outcomes in Pituitary Apoplexy Management: A Spanish Observational Multicenter Study.

Currently, the management for pituitary apoplexy (PA) has been promoted toward a more conservative approach, particularly for patients with low-grade PA scores. Our aim was to investigate trends in PA management and compare clinical presentation, therapeutic approaches, and outcomes before and after 2017, additionally to evaluate long-term outcomes in conservatively treated patients. Spanish multicenter, retrospective study. Statistical analyses compared clinical presentation and outcomes between periods, adjusting for confounders. A total of 215 patients with PA and nonfunctioning pituitary adenoma were included, with the median age of 62.2 years and 68.4% were male patients. Of which 94 (43.7%) were diagnosed before 2017 and 121 (56.3%) in 2017 or later. Conservative treatment increased from 17% before to 30.6% in the recent period (odd ratio 0.47, 95% CI 0.24-0.90, P 0.02) This trend remained significant after adjusting for hospital, age, and Knosp grade (odd ratio 0.46, 95% CI 0.22-0.89, P = .03). However, surgery remained the most frequently used therapeutic option in both periods. There were no statistically significant differences in outcomes at 3 months between periods. Surgery compared with conservative management was associated with higher permanent arginine vasopressin deficiency in both periods (0 vs 17.9%, P = .07 before 2017; 0 vs 16.7%, P = .01 after). Up to 89.7% of patients treated conservatively, presented more than 25% spontaneous tumor shrinkage, and 74.4% had more than 50% tumor reduction. Although conservative management increased in the last years, surgery remains the predominant option. Patients managed conservatively experience a lower risk of permanent arginine vasopressin deficiency, and a high proportion exhibit clinically significant tumor shrinkage over time.

Trial eligibility, treatment patterns and outcome for venetoclax-based therapy in AML: a prospective cohort study.

Venetoclax (Ven) plus hypomethylating agents are considered standard-of-care for patients with acute myeloid leukemia (AML) judged ineligible for intensive chemotherapy (IC). Real-world studies complement clinical trials, since patterns of patient selection, treatment-exposure and post-remission management may vary. This prospective observational multi-center study included 209 newly diagnosed IC-ineligible patients with a median age 75 years (interquartile range, 71-81 years). A high proportion of patients had secondary AML (53.7%), adverse-risk disease (35.3%), and complex karyotype (15.5%). At a median follow-up of 22.5 months (range 0.1-43), median overall-survival (mOS) was 11.7 months (95% Confidence Interval [CI] 9.9,15.4). Composite complete remission (CRc) was achieved in 65.2% (CR 44.4%; CRi 20.8%). Of responding patients, 21.1% underwent stem-cell transplantation. When stratified based on VIALE-A original eligibility criteria, mOS was 17.8 months for patients meeting eligibility criteria and 10.7 months for patients who did not (p=0.027). AML ontogeny (p=0.024), reduced kidney function (p=0.001), Charlson co-morbidity index (CCI; p=0.0017), ELN-risk (p=0.01) and body-mass index (p=0.0298) were significantly associated with OS. Multivariant Cox-regression analysis confirmed independent association of OS with AML ontogeny (p=0.012), CCI (p=0.033) and ELN-risk (p=0.019). Patients enrolled in the latter half of the study period demonstrated improved OS compared to those enrolled earlier (p=0.026). This prospective observational study highlights outcomes of patient subgroups, including those excluded from registration trials. (clinicaltrials.gov: #NCT03987958).

Prevalence of measurable residual disease in patients with refractory/relapsed multiple myeloma who reached complete response: a cross-sectional multicentric study

BackgroundMultiple myeloma (MM) is an incurable hematologic malignancy, and even though the complete response (CR) rate has been growing, a high percentage of patients continues to relapse. Recent research showed that most relapses may be related to the persistence of measurable residual disease (MRD). In this study, we intended to evaluate the MRD status in MM patients who reached CR in their second or third lines of treatment.MethodsThis was a cross-sectional, multicentre, non-interventional study to describe the MRD status in patients with relapsed or refractory MM (rrMM), with documented CR; adult male and female patients, from 11 Portuguese sites, in their second or third line of treatment were included. Bone marrow MRD was assessed through next-generation flow cytometry (NGF) technology.ResultsAmong the 68 subjects who gave informed consent, 48 were considered eligible for the study. Of the 48 subjects with confirmed CR, 31 (64.6%) had undetectable MRD levels. The incidence of undetectable MRD was lower in International Staging System (ISS) III patients compared with ISS I/II patients (60% vs. 70.8%; p = 0.45), and lower in patients treated without daratumumab-containing regimens compared with those treated with daratumumab-containing regimens (57.1% vs. 75.0%; p = 0.30). Notably, despite the small sample size, the incidence of undetectable MRD was significantly lower in patients with high-risk cytogenetics compared to those with standard risk (33.3% vs. 76.0%; p = 0.04).DiscussionOur results highlight the possibility of achieving undetectable MRD in the rrMM setting, especially in earlier stages and with highly effective protocols. We expect that this work leverages the implementation of larger real-world evidence studies in rrMM patients, in which MRD may also be defined as a primary endpoint.