Multicenter Retrospective Observational Study Research Articles

Diagnostic accuracy of percutaneous transthoracic needle biopsy among peripheral pulmonary lesions: a multicenter observational study

Introduction: The diagnosis of peripheral pulmonary lesions (PPL) poses a significant challenge, prompting the widespread utilization of various modalities to ensure the precision in diagnosis. This study aims to assess the diagnostic accuracy of computed tomography-guided percutaneous transthoracic needle biopsy (CT-PTNB) in the context of pulmonary malignancy. Methods and materials: This multicenter retrospective observational study, included 1317 cases of CT-PTNB performed on adult patients with PPLs from January 2018 to December 2022 in Mashhad, Iran. The pathology results of CT-PTNB from 94 cases were compared to the definitive pathology results obtained through methods such as surgery to assess the sensitivity, specificity, and overall accuracy of CT-PTNB in diagnosing of pulmonary malignancy. Results: CT-PTNB exhibits an accuracy of 82.98%, with sensitivity and specificity rates of 75.41 and 91.43%, respectively. This study underscores the issue of false-negative results in CT-PTNB and underscores the importance of integrating clinical, radiological, and additional diagnostic modality to guide diagnostic decisions. Conclusion: In this large-scale multicenter study, the accuracy of CT-PTNB for diagnosis of pulmonary malignancy is acceptable but fairly low compared to previous studies.

Causes, Diagnostic Testing, and Treatments Related to Clinical Deterioration Events Among High-Risk Ward Patients.

Timely intervention for clinically deteriorating ward patients requires that care teams accurately diagnose and treat their underlying medical conditions. However, the most common diagnoses leading to deterioration and the relevant therapies provided are poorly characterized. We aimed to determine the diagnoses responsible for clinical deterioration, the relevant diagnostic tests ordered, and the treatments administered among high-risk ward patients using manual chart review. This was a multicenter retrospective observational study in inpatient medical-surgical wards at four health systems from 2006 to 2020. Randomly selected patients (1000 from each health system) with clinical deterioration, defined by reaching the 95th percentile of a validated early warning score, electronic Cardiac Arrest Risk Triage, were included. Clinical deterioration was confirmed by a trained reviewer or marked as a false alarm if no deterioration occurred for each patient. For true deterioration events, the condition causing deterioration, relevant diagnostic tests ordered, and treatments provided were collected. Of the 4000 included patients, 2484 (62%) had clinical deterioration confirmed by chart review. Sepsis was the most common cause of deterioration (41%; n = 1021), followed by arrhythmia (19%; n = 473), while liver failure had the highest in-hospital mortality (41%). The most common diagnostic tests ordered were complete blood counts (47% of events), followed by chest radiographs (42%) and cultures (40%), while the most common medication orders were antimicrobials (46%), followed by fluid boluses (34%) and antiarrhythmics (19%). We found that sepsis was the most common cause of deterioration, while liver failure had the highest mortality. Complete blood counts and chest radiographs were the most common diagnostic tests ordered, and antimicrobials and fluid boluses were the most common medication interventions. These results provide important insights for clinical decision-making at the bedside, training of rapid response teams, and the development of institutional treatment pathways for clinical deterioration.

Utility of pan-immune-inflammation value as a predictor of the prognosis of childhood lupus.

Systemic lupus erythematosus (SLE) is a chronic inflammatory multisystemic disease. Monitoring disease activity thoughtout the disease course is important for effective management and assessment of disease outcome. To assess whether the pan-immune inflammation value (PIIV) at diagnosis could predict organ involvement and disease activity in childhood SLE (cSLE) patients after 12months of disease onst. This is an observational retrospective multicenter study that comprised cSLE patients seen and followed at the participating centers between January 2010 and December 2022. All patients met the EULAR/ACR-19 criteria, were immunosuppressive drug-naïve at the time of SLE diagnosis and had a minimal follow-up period of 12months. The data included clinical and laboratory findings and disease activity using the SLEDAI-2K. Receiver operating characteristic (ROC) curves were employed to determine the optimal cut-off value of PIIV and assess its predictive potential for disease activity, and organ involvement. A total of 125 patients (104 female) with a median age of 16.0 (IQR 5.6) years, a median age at disease onset of 10.9 (IQR 3.0) years, and a median disease duration of 4.8 (IQR 5.3) years were included. The most frequent involved organs at diagnosis were hematological (89.6%), musculoskeletal (68.8%), mucocutaneous (63.2%), and renal (58.4%). However, at a 12-month follow-up visit, the most frequent involved organs were renal (40.0%), hematological (39.2%), musculoskeletal (15.2%), and mucocutaneous (10.4%). The median PIIV at diagnosis was 139 (IQR 229.6), while the median SLEDAI was 12 (IQR 6.5) and 3.5 (IQR 7.0) at diagnosis and 12months, respectively. An optimal PIIV cut-off of 250 was found to be a predicative for disease activity, with a sensitivity of 45% and a specificity of 86%. The study revealed that the PIIV successfully predicted four systems in our cohort of patients. Our work suggests the PIIV might be a reasonable predictor for organ involvement and disease activity in newly diagnosed cSLE, though further research, particularly larger studies, is required to validate these findings, especially regarding organ involvement.

Clinical Outcomes of Maintenance Durvalumab After Definitive Concurrent Chemoradiotherapy in Unresectable Locally Advanced Stage III NSCLC According to EGFR and ALK Status: Korean Cancer Study Group LU-22-18

IntroductionThe role of maintenance durvalumab after definitive concurrent chemoradiotherapy (CCRT) in unresectable locally advanced NSCLC with EGFR mutation or ALK translocation remains unclear. We compared the effectiveness of durvalumab maintenance therapy in groups with EGFR/ALK wild-type versus those with EGFR or ALK mutations. MethodsIn this retrospective multicenter observational study, patients with locally advanced NSCLC without progression after CCRT followed by maintenance durvalumab and available molecular test results (EGFR and ALK) were eligible. The primary objective was to compare progression-free survival (PFS) between EGFR/ALK wild-type and EGFR or ALK mutant NSCLC. Secondary objectives include overall survival according to EGFR or ALK mutation and programmed death-ligand 1 (PD-L1) expression. ResultsAmong 339 patients, 279 had wild-type EGFR/ALK, 41 had EGFR mutations and 19 had ALK translocations. The median age was 68 years with 276 male individuals (81.4%) and 63 female individuals (18.6%), 165 (49.3%) had adenocarcinoma, 149 (44.5%) had squamous cell carcinoma, and 21 (6.3%) had other histologic types, 120 (35.4%) had stage IIIA, 168 (49.6%) stage IIIB, and 51 (15.0%) had stage IIIC. Most of the patients (n = 288, 85%) achieved partial response to CCRT, two (0.6%) had a complete response, and 49 patients (14.4%) had stable disease. Excluding four patients with unknown PD-L1 tumor proportion score (TPS), 16 (4.8%) had a PD-L1 TPS of 0, 168 (50.1%) had 1 to 49, and 151 (45.1%) had 50 or higher. The median PFS was 21.4 months (95% confidence interval [CI]: 17.3–25.3) for the EGFR/ALK wild-type group and 21.0 months (95% CI: 15.7–not available [NA]) for the EGFR or ALK mutant group with no significant difference (p = 0.74). Significant differences occurred in PFS on the basis of PD-L1 expression with values of 13.6 (95% CI: 10.5–NA), 18.7 (95% CI: 15.1–26.9), and 24.7 (95% CI: 20.7–NA) months for TPS of 0, 1–49, and 50 or higher, respectively (p = 0.02). ConclusionsDurvalumab maintenance therapy after definitive CCRT in unresectable locally advanced NSCLC patients with EGFR or ALK mutation demonstrates comparable clinical outcomes to those with wild-type EGFR/ALK when PD-L1 expression is present.

Comparative outcomes of selective laser trabeculoplasty delivered by optometrists compared with ophthalmologists: a UK-based multicentre observational study

BackgroundSelective laser trabeculoplasty (SLT), a National Institute for Care and Health Excellence recommended first-line treatment for open-angle glaucoma and ocular hypertension, is increasingly delivered by optometrists. This retrospective multicentre observational...

Structural and functional brain markers of cognitive impairment in healthcare workers following mild SARS-CoV-2 infection during the original stream.

Severe acute respiratory syndrome coronavirus 2 infection often involves the nervous system, leading to cognitive dysfunctions, fatigue and many other neurological signs that are becoming increasingly recognized. Despite mild forms of the disease accounting for most cases worldwide, research on the pathophysiology driving mild coronavirus disease 2019 (COVID-19) has received little attention. In this respect, recent evidence has pointed out that around 30-40% of non-critical, mild-to-moderate severity COVID-19 survivors may display cognitive disturbances several months post-illness. Hence, the impact of COVID-19 on the brain structure and function, through potential neuropathological mechanisms underpinning cognitive alterations in post-mild COVID-19 infections, remains largely unexplored. This retrospective multicentre observational cohort study, entirely based on a healthcare worker sample (n = 65; 55% females, aged 21-61), investigated the cognitive status and the structural and functional brain integrity among non-hospitalized individuals who developed mild COVID-19 symptoms during the occurrence of severe acute respiratory syndrome coronavirus 2 variants Alpha to Delta, compared with healthy controls tested before the pandemic onset. All evaluations were performed at an average of 9-month follow-up post-infection period. Participants completed a comprehensive neuropsychological assessment and structural and functional MRI exams. Radiological inspection sought to detect the presence of white matter hyperintensities on axial fluid-attenuated inversion recovery images. Global and regional grey matter integrity assessment, analysing changes in grey matter volumes and cortical thinning, and functional connectivity alterations of resting-state brain networks were also conducted. Regression analyses tested the relationships between the presence of specific cognitive impairments and potential structural and functional brain findings. Our results revealed that clinical, cognitive screening and neuropsychological examinations were average between both groups, except for specific impairments related to executive functions in the mild COVID-19. Compared to healthy controls, mild COVID-19 subjects exhibited increased juxtacortical white matter hyperintensities, thalamic and occipital volume loss and diminished resting-state functional connectivity involving the left precuneus and cuneus in default-mode network and affecting the right angular gyrus and left precuneus in the dorsal attentional network. Reduced thalamic volume was the only variable selected in the final model explaining the observed executive function impairment in mild COVID-19. The presence of cognitive, structural and functional brain abnormalities over time suggests that the action of widespread neurovascular and inflammatory phenomena on the nervous system might also occur in mild forms following COVID-19 infection rather than permanent brain damage linked to the direct or indirect action of the virus. Our findings emphasize the need to pay attention to the long-term brain-related consequences of mild COVID-19 infections during the original stream.

Assessment of large-scale imaging practices in patients with acute brain hemorrhage in French emergency departments: Emergency imaging practices in hemorrhagic stroke

ObjectiveIntracerebral hemorrhage (ICH) is a life-threatening condition, where imaging plays a crucial role but remains poorly standardized. Our main objective was to analyze the imaging protocols used during the acute phase of ICH and ascertain the proportion of patients diagnosed with secondary hemorrhage. Patients and methodsA multicenter retrospective observational study was conducted across over 100 French hospitals affiliated with a national tele-imaging network dedicated to emergency imaging. Among patients managed in the “Stroke Alert” pathway for suspected acute stroke from March 2021 to April 2023, those with ICH diagnosed within 24 h of symptoms onset were identified. Their imaging reports were reviewed to identify the imaging modality used and protocols performed and investigate whether a secondary cause was identified. ResultsOf the 18,356 patients included in the ”Stroke Alert” pathway, 662 cerebral hemorrhages were identified (3.6 %). Computed tomography (CT) was the most widely used imaging modality in the acute phase (71.8 % of examinations). Vascular imaging was performed in 78 % of patients with cerebral hemorrhage, most often CT angiography or TOF magnetic resonance angiography. A secondary cause was identified in 8.2 % (54/662) of cerebral hemorrhages, including vascular imaging in the vast majority of cases (92.6 %). ConclusionOptimization and standardization of imaging protocols in the acute phase of ICH is essential to improve the detection of its secondary causes, particularly vascular, requiring urgent treatment. Vascular imaging improves their early detection.

Análisis multicéntrico del manejo quirúrgico y tratamiento adyuvante de los pacientes con melanoma y positividad en la biopsia selectiva del ganglio centinela

ObjectivesTo determine the evolution of the indication for CLND in patients with a positive SLNB, as well as the characteristics associated with its performance. Material and methodsWe conducted a multicenter retrospective observational study with patients with skin melanoma and positive sentinel lymph nodes diagnosed from 2017 through 2022 at 8 Spanish centers and 1 Italian center. ResultsA total of 430 patients were included, 54% men, with 358 (75.1%) aged between 45 and 80 years. A total of 133 cases (31%) exhibited Breslow thickness > 4mm, 206 cases (49.1%) were ulcerated, and in 213 cases (55.7%), lymph node metastasis was > 1mm. Isolated lymphadenectomy or followed by adjuvant therapy was performed in 146 patients (34.1%). After multivariate logistic regression, the factors associated with the performance of CLND were Breslow > 4mm, the acral lentiginous melanoma histological subtype, lymph node metastasis size > 1mm, extracapsular spread, and the participant hospital. Age > 80 years was inversely associated. ConclusionWhile the frequency of CLND in patients with melanoma and positive SLNB has decreased, the indication for systemic adjuvant therapy in these patients has increased. However, CLND is still indicated in patients with high-risk characteristics.

Predictors of success in left bundle branch area pacing with stylet-driven pacing leads: a multicenter investigation.

Although left bundle branch area pacing (LBBAP) is an emerging conduction system pacing modality, it is unclear which parameters predict procedural success and how many implant attempts are acceptable. This study aimed to assess predictors of successful LBBAP, left bundle branch (LBB) capture, and factors associated with the number of LBBAP implant attempts. This retrospective observational multicenter study was conducted in Korea. LBBAP was attempted in 119 patients; 89.3% of patients had bradyarrhythmia (atrioventricular block 82.4%), and 10.7% of patients had heart failure (cardiac resynchronization therapy) indication. Procedural success and electrophysiological and echocardiographic parameters were evaluated. The acute success rate of lead implantation in LBBAP was 95.8% (114 of 119 patients) and that of LBB capture was 82.4% (98 of 119 patients). Fewer implant attempts were associated with LBBAP success (three or fewer vs. over three times, p = 0.014) and LBB capture (three or fewer vs. over three times, p = 0.010). In the multivariate linear regression, the patients with intraventricular conduction delay (IVCD) required a greater number of attempts than those without IVCD [estimates = 2.33 (0.35-4.31), p = 0.02], and the larger the right atrial (RA) size, the more the attempts required for LBBAP lead implantation [estimates = 2.08 (1.20-2.97), p < 0.001]. An increase in the number of implant attempts was associated with LBBAP procedural failure and LBB capture failure. The electrocardiographic parameter IVCD and the echocardiographic parameter RA size may predict the procedural complexity and the number of lead implant attempts for LBBAP.

Evaluation of continuous positive airway pressure adherence and its contributing factors

BackgroundContinuous positive airway pressure (CPAP) adherence may vary based on the study design and country. ObjectivesTo investigate long-term CPAP adherence and elucidate associated factors. MethodsA multicenter retrospective observational cohort study was conducted over two years. The study included patients diagnosed with obstructive sleep apnea who were prescribed CPAP (n = 1261). Adherence was assessed for 90 days and 365 days. Centers for Medicare and Medicaid Services (CMS) criteria (≥4 h/night on ≥70 % of nights) and research adherence criteria (≥4 h/night during the observational period) were used. Factors influencing CPAP adherence (CMS criteria) during 90 and 365 days were also evaluated. Continuous variables were categorized into low, middle, and high classes, and logistic regression analysis with interaction was performed. ResultsCPAP adherence to CMS criteria for 90 and 365 days was 45.6 % and 44.7 %, respectively, whereas adherence to research criteria was 57.0 % and 54.1 %, respectively. Middle age, high age, and high apnea ratio independently increased CPAP adherence. Conversely, a high rapid eye movement apnea-hypopnea index ratio decreased CPAP adherence. Although high body mass index (BMI) had no independent effect on adherence, its interaction with high 3 % oxygen desaturation index increased 90-day CPAP adherence. However, high BMI decreased 90-day CPAP adherence in males. The interaction between middle age and high BMI was associated with decreased CPAP adherence over 365 days. ConclusionsAdherence to CPAP in real-world settings is modest. Various factors influence CPAP adherence. BMI may exert varied effects on CPAP adherence depending on the accompanying factors.

Immunological Tumor Microenvironment of Solitary Fibrous Tumors-Associating Immune Infiltrate with Variables of Prognostic Significance.

Solitary fibrous tumors (SFTs) are morphologically heterogeneous tumors characterized by the NAB2::STAT6 gene fusion. Clinical outcomes may vary widely, and while most cases have favorable outcomes, some can progress to aggressive disease, manifesting as recurrence and metastasis, and ultimately resulting in patient death. Herein, we analyze the immunological tumor microenvironment (ITME) of SFTs, aiming to determine its prognostic value and correlation with established risk stratification systems (RSSs). A retrospective observational multicenter study of 52 fusion-confirmed SFTs with clinical follow-up data. Immunohistochemical analysis including CD163, CD68, CD3, CD8, CD20, PDL-1, PD-1, and LAG1 were evaluated in tissue microarrays, using an analog scale with scores ranging from 0 to 3 (0 = ≤9, 1 = 10-49, 2 = 50-99, and 3 = >100 positive cells per 10 high-power fields). The expression of these markers was correlated with clinical outcomes, morphological characteristics previously evaluated in whole slide tissue sections (hypercellularity/hypocellularity, round-oval or spindle dominant constituent cell (DCC) morphology, and necrosis), Ki67, overall survival, and RSS. Only one of the fifty-two cases studied showed progression. In the multivariate analysis, neither the presence nor absence of immune cells (B-lymphocytes, T-lymphocytes, and macrophages) showed any association with the assessed RSSs (Demicco, Sugita, G-score, and Huang). Interestingly, the case that showed progression had high immune infiltrate with expression of CD68, CD163, CD8, and CD20 markers (score of 3). Round-oval cell morphology was associated with the presence of higher levels of CD163 macrophages. Lastly, the scant presence of CD20+ lymphocytes correlated with less necrosis, and cases with higher PDL-1 expression correlated with increased Ki67 values. All cases were negative for LAG-1 and PD-1. SFT ITME components correlated with independent variables with prognostic significance. Nevertheless, ITME did not correlate with RSS scores.

The polymyxin-B direct hemoperfusion OPTimal Initiation timing with Catecholamine PMX-OPTIC study: A multicenter retrospective observational study.

Polymyxin-B direct hemoperfusion (PMX-DHP) is an endotoxin adsorption column-based blood purification therapy. Since one of the most potent effects of PMX-DHP is blood pressure elevations, it may be the most effective when it is introduced at the time when the need for vasopressors is the greatest, which, in turn, may reduce mortality. A multicenter retrospective study was conducted at 24 ICUs in Japan. In each ICU, the 20 most recent consecutive cases of septic shock treated with PMX-DHP were analyzed. The duration between the time of the peak vasopressive agent dose, expressed as the noradrenaline equivalent dose (NEq), and the time of PMX initiation was evaluated. The primary outcome was 28-day mortality, and a multivariable analysis was performed to investigate factors associated with mortality. A total of 480 septic shock patients were included in the analysis. Among all patients, the 28-day mortality group was older, more severely ill, and had a higher body mass index. The NEq peak and NEq on PMX-DHP initiation were both higher in deceased patients. Regarding the timing of PMX-DHP initiation from the NEq peak, -4 << 4 h had more survivors (229/304, 75.3%) than ≤-4 h (50/75, 66.7%) and ≥4 h (66/101, 65.4%) (p = 0.085). When -4 << 4 h was assigned as a reference, the timing of PMX-DHP initiation from the NEq peak of ≤-4 h had an odds ratio of 1.96 (1.07-3.58), p = 0.029, while ≥4 h had an odds ratio of 1.64 (0.94-2.87), p = 0.082 for 28-day mortality, in the multivariable regression analysis. A spline curve of the relationship between the probability of death and the timing of PMX-DHP initiation from the NEq peak showed a downward convex curve with a nadir at timing = 0. The odds ratios of the timing of PMX-DHP initiation other than -4 << 4 h were significantly higher in an older age, male sex, lower BMI, more severe illness, and higher oxygenation. The induction of PMX-DHP at the time of the peak vasopressor dose correlated with lower mortality. PMX-DHP is one of the options available for elevating blood pressure in septic shock, and its initiation either too early or late for shock peak may not improve the outcome.

Hospitalisations for non-specific low back pain in people presenting to South Australian public hospital emergency departments.

The present study sought to investigate predictors of hospitalisation in adults diagnosed with non-specific low back pain (LBP) and/or sciatica from an ED. A 5-year, multicentre retrospective observational study was conducted across six public hospitals (metropolitan and regional) using data from electronic medical records. Patient presentations were identified using LBP diagnostic codes and key data extracted (patient demographics, clinical activity, discharge destination). Descriptive statistics and logistic regression were used to measure associations between identified variables and hospitalisation. There were 11 709 ED presentations across the study period. People aged ≥65 years (odds ratio [OR] 2.84, 95% confidence interval [CI] 2.61-3.10) and those who arrived at the ED via ambulance (age-adjusted OR 2.68, 95% CI 2.44-2.95) were more likely to be hospitalised. People were also more likely to be hospitalised when triaged as more urgent, when blood tests or advanced spinal imaging were ordered, and when i.v./subcutaneous opioids or oral benzodiazepines were administered. Hospitalisation rates for LBP were lower in regional hospitals, in people residing in lower socioeconomic areas and in Indigenous Australians. Certain patient characteristics and ED clinical activity are associated with hospitalisations for LBP. Understanding these factors will better inform the design and delivery of appropriate high-quality care.

Structured training pathway for robotic colorectal surgery: Short-term outcomes from five UK centres.

The aim of this study was to assess the short-term outcomes of robotic colorectal surgery implemented through a structured, standardized training pathway in five colorectal centres in the United Kingdom. A multicentre retrospective observational study was conducted, involving 523 consecutive patients who underwent robotic colorectal resection between 2015 and 2019. All participating centres followed the European Academy of Robotic Colorectal Surgery training pathway. Patient data, including demographics, operative details, postoperative outcomes and pathology results, were collected and analysed. The study included 447 rectal resections and 76 colonic operations. The median age of the patients was 64.7 years, with the majority of patients (70%) being men. The mean body mass index was 27.4 kg/m2, and 89.7% of the patients underwent surgery for malignancy. The overall conversion rate to open surgery was 4.2%. The median length of stay was 6 days and there was no 30-day mortality. The readmission and reoperation rates were 8.8% and 7.3%, respectively. The anastomotic leak rate was 4.1% for rectal resections and 3.9% for colonic resections. Pathological examination showed a positive circumferential resection margin rate of 2.6%. Through the implementation of a structured, standardized training pathway, the participating colorectal centres in the UK achieved safe and effective robotic colorectal surgery pathways with favourable short-term oncological and clinical outcomes. Further studies examining long-term and functional outcomes are needed to assess the broader impact of robotic surgery in colorectal procedures.

Outcomes of chronic myeloid leukemia patients after therapeutic failure to conventional tyrosine kinase inhibitors and asciminib

Patients with chronic myeloid leukemia (CML) who have failed conventional tyrosine kinase inhibitors (cTKIs) and asciminib constitute a complex group of patients with few therapeutic options. A retrospective descriptive multicenter observational study was carried out including patients with CML who had presented a therapeutic failure to ≥ 2 cTKIs and asciminib, and had received or were not candidates to ponatinib. Of the 19 patients enrolled, 8 patients failed asciminib due to intolerance and 11 due to resistance. The most common strategy for intolerant patients was to initiate a previously administered cTKI (6/8) with dose adjustments or symptomatic management of adverse events (AEs). Of the patients who failed due to resistance, only patients who underwent progenitor transplantation achieved profound long-term responses. A frequent strategy was to use ponatinib (4/11) in patients previously considered non-candidates, with poor responses in patients in whom dose reductions were used, and severe AEs in patients at standard doses. In the remaining patients, cTKIs and other agents (interferon, hydroxyurea, citarabine, busulfan) were used with poor responses. Patients who progressed to advanced stages had a dismal prognosis. With a median follow-up of 11.2 months, overall survival of the global cohort was 73%; 100% for intolerant patients, 71% for resistant patients and 25% for those who discontinue asciminib in accelerated/blastic phase.

Retrospective study on the outcomes and satisfaction with endometrial ablation by bipolar energy (NovaSure®) for the treatment of heavy menstrual bleeding.

To determine the effectiveness, safety, and participant satisfaction with endometrial ablation by bipolar energy (NovaSure®) in the treatment of heavy menstrual bleeding (HMB), and to investigate factors associated with poorer outcomes. Multicenter retrospective observational study based on medical record review of the outcomes related to endometrial ablation by the bipolar-energy technique procedure to treat HMB in the setting of three university teaching hospitals in Spain. A total of 333 women were included in the study. Most bipolar-energy ablations were successful (85.12%; n = 269 out of 316), with amenorrhea the most frequent outcome (39.6%, n = 131 out of 316). The majority of participants had no complications (95.5%; n = 317 out of 332), and of those who did, only 2.1% were related to the technique. No further treatment was required for HMB in 82.8% of women (n = 274 out of 331), and surgery was avoided in 91.8%; only 5.9% of women underwent ablation-related hysterectomy. In women with previous transverse cesarean sections (CS), 91.0% avoided subsequent surgical treatment. Eighty-six percent of women (n = 221 out of 257) were satisfied with the procedure. Bipolar-energy ablation is very effective and safe for the treatment of HMB and yielded a high rate of participant satisfaction in our setting. The presence of comorbidities or previous CSmay slightly reduce the effectiveness of the method, while performing concomitant surgery (mainly curettage) increases the rate of complications. Notably, despite the known increased risk of hysterectomy, most participants with previous CSs who underwent ablation avoided major surgery.

Safety and Efficacy of Conversion Therapy After Systemic Chemotherapy in Advanced Esophageal Cancer with Distant Metastases: A Multicenter Retrospective Observational Study.

Patients with esophageal squamous cell carcinoma (ESCC) with distant metastasis were treated with systemic chemotherapy. Recent advances in multimodal treatments have made conversion therapy a viable option for patients with incurable ESCC. We aimed to assess the safety and efficacy of conversion therapy for ESCC with distant metastases. Conversion therapy was defined as surgery or chemoradiotherapy (CRT) used to cure tumors that were previously considered incurable because of distant metastasis. We conducted a retrospective review of patients who underwent ESCC conversion therapy and assessed the treatment outcomes, including adverse events and survival rates. A total of 147 patients from 22 institutions were included. Systemic chemotherapy was initially administered to all patients. The most common M1 factor was the para-aortic lymph node, accounting for 55% of cases. Following the initial treatment, 116 patients underwent surgery, with 31 receiving CRT as conversion therapy. Postoperative complications in surgery patients included pneumonia (16%), anastomotic leakage (7%), and recurrent laryngeal nerve palsy (6%). During CRT, 18% of patients developed grade 3 or higher non-hematological toxicities. The 5-year overall survival (OS) rate was 31.7%. Pathological responders had significantly longer OS than non-responders (hazard ratio 0.493, p=0.012). The distribution of distant metastasis, regimen type, clinical response, and conversion therapy modality did not have a significant impact on OS. Conversion therapy can be safely performed for ESCC with distant metastasis and has a favorable prognosis.

Development and validation of machine-learning models of diet management for hyperphenylalaninemia: a multicenter retrospective study

BackgroundAssessing dietary phenylalanine (Phe) tolerance is crucial for managing hyperphenylalaninemia (HPA) in children. However, traditionally, adjusting the diet requires significant time from clinicians and parents. This study aims to investigate the development of a machine-learning model that predicts a range of dietary Phe intake tolerance for children with HPA over 10 years following diagnosis.MethodsIn this multicenter retrospective observational study, we collected the genotypes of phenylalanine hydroxylase (PAH), metabolic profiles at screening and diagnosis, and blood Phe concentrations corresponding to dietary Phe intake from over 10 years of follow-up data for 204 children with HPA. To incorporate genetic information, allelic phenotype value (APV) was input for 2965 missense variants in the PAH gene using a predicted APV (pAPV) model. This model was trained on known pheno-genotype relationships from the BioPKU database, utilizing 31 features. Subsequently, a multiclass classification model was constructed and trained on a dataset featuring metabolic data, genetic data, and follow-up data from 3177 events. The final model was fine-tuned using tenfold validation and validated against three independent datasets.ResultsThe pAPV model achieved a good predictive performance with root mean squared error (RMSE) of 1.53 and 2.38 on the training and test datasets, respectively. The variants that cause amino acid changes in the region of 200–300 of PAH tend to exhibit lower pAPV. The final model achieved a sensitivity range of 0.77 to 0.91 and a specificity range of 0.8 to 1 across all validation datasets. Additional assessment metrics including positive predictive value (0.68–1), negative predictive values (0.8–0.98), F1 score (0.71–0.92), and balanced accuracy (0.8–0.92) demonstrated the robust performance of our model.ConclusionsOur model integrates metabolic and genetic information to accurately predict age-specific Phe tolerance, aiding in the precision management of patients with HPA. This study provides a potential framework that could be applied to other inborn errors of metabolism.

Cardiac manifestations and outcomes of COVID-19 vaccine-associated myocarditis in the young in the USA: longitudinal results from the Myocarditis After COVID Vaccination (MACiV) multicenter study

We aimed to study the clinical characteristics, myocardial injury, and longitudinal outcomes of COVID-19 vaccine-associated myocarditis (C-VAM). In this longitudinal retrospective observational cohort multicenter study across 38 hospitals in the United States, 333 patients with C-VAM were compared with 100 patients with multisystem inflammatory syndrome inchildren (MIS-C). We included patients ≤30 years of age with a clinical diagnosis of acute myocarditis after COVID-19 vaccination based on clinical presentation, abnormal biomarkers and/or cardiovascular imaging findings. Demographics, past medical history, hospital course, biochemistry results, cardiovascular imaging, and follow-up information from April 2021 to November 2022 were collected. The primary outcome was presence of myocardial injury as evidenced by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. Patients with C-VAM were predominantly white (67%) adolescent males (91%, 15.7±2.8 years). Their initial clinical course was more likely to be mild (80% vs. 23%, p<0.001) and cardiac dysfunction was less common (17% vs. 68%, p<0.0001), compared to MIS-C. In contrast, LGE on CMR was more prevalent in C-VAM (82% vs. 16%, p<0.001). The probability of LGE was higher in males (OR 3.28 [95% CI: 0.99, 10.6, p=0.052]), in older patients (>15 years, OR 2.74 [95% CI: 1.28, 5.83, p=0.009]) and when C-VAM occurred after the first or second dose as compared to the third dose of mRNA vaccine. Mid-term clinical outcomes of C-VAM at a median follow-up of 178days (IQR 114-285 days) were reassuring. No cardiac deaths or heart transplantations were reported until the time of submission of this report. LGE persisted in 60% of the patients at follow up. Myocardial injury at initial presentation and its persistence at follow up, despite a mild initial course and favorable mid-term clinical outcome, warrants continued clinical surveillance and long-term studies in affected patients with C-VAM. The U.S. Food and Drug Administration.

Recurrence-Independent Progressive Inner-Retinal Thinning After Optic Neuritis: A Longitudinal Study.

Longitudinal changes in the inner retina in patients with optic neuritis (ON) may be helpful in monitoring patients and determining maintenance treatment. The aim of this study was to investigate longitudinal changes in the inner retina after subsiding of acute demyelinating ON and to identify the factors associated with such changes. In this multicenter retrospective observational study, we reviewed the medical records of 77 patients with ON, including 23 with neuromyelitis optica spectrum disorder with aquaporin 4 (AQP4)-immunoglobulin G (IgG) (AQP4 group), 23 with myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOG group), 18 with multiple sclerosis (MS group), and 13 with idiopathic ON (iON group). We measured the thickness of the peripapillary retinal nerve fiber layer (pRNFL) and the macular ganglion cell-inner plexiform layer (mGCIPL) using optical coherence tomography (OCT) at baseline and at follow-up examinations (mean follow-up duration, 29.6 ± 8.6 months; mean number of OCT, 4.2 ± 1.2) in the absence of ON recurrence. The estimated rate of pRNFL thinning in the AQP4, MOG, MS, and iON groups was 0.66 (95% confidence interval, 0.35-0.97), 0.35 (0.04-0.66), 0.53 (0.16-0.90), and 0.25 (-0.18 to 0.68) μm/year, respectively, indicating that, in the iON group in contrast to the other groups, there was no significant decrease of pRNFL thickness. Among the AQP4, MOG, and MS groups, there was no significant difference in the rate of pRNFL thinning (P = 0.560). The rate of mGCIPL thinning in the AQP4 and MOG groups was 0.25 (0.04-0.46) μm/year and 0.38 (0.23-0.53) μm/year, respectively. Meanwhile, the rate of mGCIPL change in the MS and iON groups was 0.04 (-0.12 to 0.19) and 0.00 (-0.17 to 0.16) μm/year, respectively, which indicates that there was no significant mGCIPL thinning in the latter 2 groups. Between the AQP4 and MOG groups, meanwhile, the rate of mGCIPL change did not significantly differ (P = 0.295). Age older than 40 years was associated with significant progression of mGCIPL thinning (P = 0.005). We noted inner retina thinning progression independent of relapse activity in AQP4-ON, MOG-ON, and MS-ON. Because subclinical neuroaxonal damage continues to be incurred after an acute attack of ON subsides despite suppression of new attacks, long-term follow-up and neuroprotection should be considered to be integral to the treatment of patients with ON.