To investigate the clinical characteristics of patients with saddle pulmonary embolism (SPE) among those with intermediate- to high-risk acute pulmonary embolism (APE).

A comparative study. Place and Duration of the Study: Department of Interventional Vascular Surgery, the First Hospital of Putian City, Putian, China, from May 2017 to October 2024.

Combined anticoagulation and interventional therapy was administered to all enrolled intermediate- to high-risk APE patients (with right ventricular dysfunction and/or elevated cardiac biomarkers, or haemodynamic instability) per the study protocol. Based on whether SPE was identified on computed tomography pulmonary angiography, patients were divided into the SPE group and the non-SPE group. Clinical characteristics, cardiac biomarkers, imaging features, and clinical outcomes were compared between the two groups.

When comparing the groups, no significant differences were observed in N-terminal pro-B-type natriuretic peptide, right ventricular diameter/left ventricular diameter, and peripheral pulmonary artery obstruction index before and after treatment (p >0.05). However, the SPE group had higher levels of cardiac troponin I than the non-SPE group before and after treatment (p <0.05). There was no significant difference in in-hospital mortality between the two groups (p = 0.653). In the SPE group, the saddle embolism resolved completely in 94.74% of patients after treatment.

Patients with SPE may experience more severe myocardial injury. The short-term resolution of the saddle embolism after treatment appears not to be a critical factor affecting treatment response.

Intermediate- to high-risk, Acute pulmonary embolism, Computed tomography pulmonary angiography, Saddle pulmonary embolism, Clinical characteristics.

The Nijmegen Questionnaire (NQ) is used to identify Dysfunctional Breathing (DB) in individuals with asthma. However, it has not been validated for use in children and adolescents.

This study aimed to validate a Swedish NQ for this population.

Participants aged 10-17 years with asthma were included (n = 124). In Cohort I (n = 22), audiotaped semi-structured interviews were conducted to adapt and refine the questionnaire analyzed by qualitative content analysis, resulting in NQ version 1. Forty-eight participants (11 from Cohort I, 37 new) then completed version 1 to assess internal redundancy, consistency (Spearman's Rho, Cronbach's alpha) and item clarity, leading to version 2. Cohort II (n = 60 new) completed NQ version 2 alongside the Paediatric Asthma Quality of Life Questionnaire (PAQLQ) and Childhood/Adult Asthma Control Test (cACT/ACT) to assess construct validity. Cohort III (n = 54, 48 from Cohort II, 6 new) completed NQ version 2 again after 2 weeks for test-retest reliability.

Content analysis prompted revisions for clarity and relevance. Internal redundancy ranged from r_s = 0.00-0.69 and internal consistency was 0.85 (Cronbach's alpha). The NQ correlated moderately with cACT/ACT (r_s = -0.54) and PAQLQ subscales Symptoms, Activity limitation and Emotional function, r_s -0.52, -0.48, -0.39 (CI 0.32;0.70, 0.24;0.66, 0.14;0.60) respectively. Test-retest reliability was 0.86 (Kw) (p < 0.0001).

The Swedish Paediatric NQ seems to be a valid and reliable tool for identifying DB in children and adolescents with asthma.

Peritonsillitis, including peritonsillar abscess and cellulitis, is a common deep neck infection often considered a complication of pharyngotonsillitis. However, population-based data on patient characteristics, clinical presentation, and care pathways are limited.

We conducted a population-based registry study in Region Kronoberg, Sweden (2012-2016), including all episodes of peritonsillitis and pharyngotonsillitis diagnosed in primary health care (PHC) and hospitals. New episodes were defined as diagnoses separated by ≥ 30 days. Patient characteristics, recent pharyngotonsillitis, and referral pathways between PHC and specialist care were described. Incidence rates and temporal trends were estimated to provide population context.

A total of 607 peritonsillitis episodes were identified in 555 patients. Incidence peaked in late adolescence and young adulthood, remained low in children and older adults, and showed no sex differences within age groups. Only 23% of episodes were preceded by pharyngotonsillitis within 30 days (median interval: 2 days), increasing to 29% when restricting the analysis to cases confirmed in the ear, nose, and throat (ENT) department. Most patients (74%) were first diagnosed in PHC, and 71% of these were subsequently managed in the ENT department. Overall, 85% of all episodes involved initial PHC management. Incidence of peritonsillitis declined over time in parallel with pharyngotonsillitis at the population level.

Peritonsillitis predominantly affects adolescents and young adults and commonly presents without a recent documented sore throat. PHC plays a central role in initial assessment and referral, with most patients subsequently managed in specialist care. These findings provide population-level insights into patient characteristics and care pathways, with implications for early recognition and management in PHC.

Obstructive sleep apnea (OSA) is a known risk factor for coronary artery disease (CAD), but its phenotypic variations and their impact on cardiovascular risk remain unclear. Recent studies suggest that a high periodic limb movement index (PLMI) and a high arousal index OSA phenotype may contribute to cardiovascular disease. This study aims to assess the association between this phenotype and CAD in patients undergoing preprocedural screening for coronary artery bypass grafting (CABG).

This case-comparison study analyzed a prospective adult patient group undergoing polysomnography before CABG, compared to an age- and gender-matched retrospective group undergoing polysomnography for employment screening. Sleep parameters, including PLMI, arousal index, apnea-hypopnea index (AHI), and sleep onset latency, were assessed. Statistical analysis, including chi-square tests, Fisher's exact test, and multivariable logistic regression, was conducted to evaluate associations between sleep disturbances and CAD.

CAD patients had significant differences in the amount of abnormal PLMI, arousal index, and AHI values compared to the non-CAD group (p = 0.0002, p = 0.002, and p = 0.015, respectively). Multivariable regression identified high PLMI and arousal index as the strongest associations of CAD.

A high PLMI/high arousal index OSA phenotype may increase cardiovascular risk. Identifying high-risk OSA phenotypes could improve early CAD screening and intervention strategies. Further research is needed to explore underlying mechanisms.

Acute respiratory distress syndrome (ARDS) is a severe clinical condition characterized by acute hypoxemic respiratory failure (AHRF) and diffuse pulmonary inflammation, which can be triggered by diverse intrapulmonary, extrapulmonary, and host-related factors. Over recent decades, basic research and clinical trials have significantly advanced our understanding of ARDS mechanisms, and effective comprehensive critical care interventions, including lung-protective ventilation, prone positioning, and individualized fluid management, have been widely implemented. Nevertheless, ARDS continues to be associated with substantial morbidity and mortality, and its marked clinical and biological heterogeneity remains a major obstacle to effective management and therapeutic translation. This review summarizes current evidence on ARDS epidemiology, etiology, pathophysiology, diagnosis, and clinical management. We also trace the evolution of diagnostic criteria, including the latest global definition, and critically examine disease heterogeneity, recent advances in critical care strategies, emerging therapeutic approaches, barriers to clinical translation, and future research priorities. Particular emphasis is placed on integrating clinical, physiological, and multi-omics data to support biologically and clinically meaningful patient phenotyping grounded in disease mechanisms. Building on this phenotypic stratification, innovative trial designs, including predictive enrichment and adaptive platform trials, may facilitate the development of more individualized, targeted, and dynamically adjusted treatment strategies for ARDS. In summary, establishing a precision medicine framework for ARDS that integrates etiology, mechanistic insights, phenotype-based patient stratification, individualized therapeutic strategies, and long-term management will be essential to address current challenges and improve patient outcomes.

Preoperative optimisation programmes aim to reduce complications after total joint arthroplasty (TJA), yet long-term effects on superficial surgical site infections (SSI), periprosthetic joint infections (PJI) and overall health remain unclear. This study evaluated the long-term impact of preoperative optimisation in cooperation with hospital and primary healthcare on infection outcomes and general health following elective primary lower extremity TJA.

In this prospective quasi-experimental study, 1484 patients undergoing TJA were followed postoperatively. The intervention group underwent a multifactorial optimisation process 6-12 months preoperatively, while the control group received conventional preparation.

Landspitali University Hospital and Primary Health Care in Iceland treating patients undergoing primary TJA between August 2018 and December 2022.

The intervention group comprised 746 patients and the control group 738. Of the intervention group, 77% received surgery during the COVID-19 pandemic versus 5% in the control group.

Outcomes included incidence of superficial SSI at 1 year and PJI and postoperative health and mortality at 3 years.

Superficial SSI occurred in 5.9% of the intervention group versus 7.9% in the control group (HR 0.67; 95% CI 0.45 to 1.01), with 95% versus 98% appearing within 6 weeks. PJI occurred in 2.0% versus 1.1%, respectively (HR 1.80; 95% CI 0.76 to 4.30). Most PJIs (80 vs 88%) followed superficial SSI, the majority within a week. Progression from superficial SSI to PJI was higher in the intervention group (27.3% vs 12.1%). No significant differences were found in postoperative health or mortality.

At 1 year postoperatively, no significant long-term reductions in superficial SSI were found, nor at 3 years in PJI or general health. Confounding factors, including COVID-19-related disruptions and organisational changes, may have influenced outcomes. The study emphasises the importance of prospective evaluation of preoperative optimisation strategies as well as organisational and practice changes on patient outcome.

NCT05399186.

To compare the reliability of four commonly used structured tools for risk-of-bias assessment in prognostic cohort studies and evaluate their agreement with expert appraisal.

Methodological comparison study.

Secondary analysis of published prognostic cohort studies in patients with acute pulmonary embolism from a previously conducted systematic review.

Sixty-three cohort studies assessing the prognostic role of echocardiography in patients with acute pulmonary embolism.

Four independent reviewers assessed study quality/risk of bias using the Newcastle-Ottawa Scale (NOS), Risk Of Bias in Non-Randomised Studies of Interventions (ROBINS-I), Quality In Prognostic Studies (QUIPS) and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Concomitantly and independently, expert reviewers' implicit global judgements were used as an external comparator. Inter-rater reliability, agreement with expert appraisal, internal consistency and floor/ceiling effects were assessed.

Inter-rater agreement was fair for NOS (Gwet's agreement coefficient 1, 0.25, 95% CI 0.15 to 0.34), ROBINS-I (0.38, 95% CI 0.28 to 0.47) and QUADAS-2 (0.35, 95% CI 0.27 to 0.43) and almost perfect for QUIPS (0.85, 95% CI 0.73 to 0.93). Agreement with expert appraisal was limited for all tools except ROBINS-I, which showed fair concordance. QUIPS frequently classified studies as low risk of bias, suggesting potential overestimation of study quality. Internal consistency was generally low across tools, while ceiling effects were observed for NOS and QUIPS. ROBINS-I showed the most balanced distribution of ratings.

Structured tools for risk-of-bias assessment in prognostic cohort studies have variable reliability and limited agreement with expert appraisal. ROBINS-I showed the strongest concordance with expert judgement, whereas QUIPS may provide optimistic ratings. These findings support further refinement and standardisation of risk-of-bias assessment methods for observational prognostic research.

COVID-19 presents a wide spectrum of clinical outcomes, and early identification of patients at high-risk for a worse disease prognosis remains a critical challenge. In this study, we performed a six-week longitudinal proteomic analysis of 197 plasma samples collected weekly from 44 hospitalized COVID-19 patients. Temporal profiling revealed 828 proteins with significant time-dependent abundance changes, clustering into an early acute-phase and inflammatory response group that gradually declined toward the cohort's overall mean profile over time and a group of late vesicle-mediated transport and antigen binding that were decreased in the first weeks. Global correlation mapping identified six coregulated protein modules, notably including insulin-like growth factor binding proteins. Proteomic divergence between survivors and nonsurvivors became pronounced from week 4 onward. The proteins HPR, IGFALS, PF4, LPA, and COLEC11 achieved AUCs > 0.72 for mortality prediction in the first 2 weeks, and an SVM model combining these markers yielded an AUC of 0.801. These findings demonstrate that plasma proteome trajectories capture dynamic host responses and generate candidate prognostic markers, offering a promising strategy for risk stratification and guiding targeted interventions in COVID-19.

Cefepime/enmetazobactam (FEP/META) is a novel β-lactam/β-lactamase inhibitor combination with activity against Enterobacterales, including extended-spectrum β-lactamase-producing isolates, but real-world clinical data outside randomized trials remain limited. We conducted a retrospective multicenter descriptive study across 13 Italian hospitals. Eligible patients had infections caused by Enterobacterales and received ≥72 h of cefepime/enmetazobactam therapy (alone or in combination with other antimicrobials) under a compassionate-use program. Thirty-two patients were included. The most frequently isolated pathogens were Escherichia coli (16/32, 50.0%) and Klebsiella pneumoniae (13/32, 40.6%). Extended-spectrum β-lactamase production was documented in 29/32 isolates (90.6%), while β-lactam/β-lactamase inhibitor resistance and fluoroquinolone resistance were each observed in 18/32 isolates (56.2%). Four isolates were ertapenem-resistant but remained susceptible to imipenem and meropenem; no carbapenemase production was confirmed. FEP/META was safely administered as targeted therapy in most cases and was used both as monotherapy and in combination regimens, according to clinical severity and source of infection. Clinical cure was achieved in all patients, and microbiological eradication was documented in 25/32 cases (78.1%). No in-hospital deaths were recorded. Despite the inherent limitations of retrospective real-world studies, our findings suggest that cefepime/enmetazobactam may be a well-tolerated component of carbapenem-sparing treatment strategies for selected documented Enterobacterales infections. In 32 real-world documented Enterobacterales infections, cefepime/enmetazobactam achieved 100% clinical cure and 78.1% microbiological eradication, with favorable tolerability.IMPORTANCEAntibiotic-resistant infections are an increasing challenge, and clinicians need effective treatments that can reduce reliance on carbapenems, which are often considered last-line antibiotics. Cefepime/enmetazobactam is a new antibiotic combination with activity against resistant Enterobacterales, particularly ESBL-producing bacteria, but real-world clinical data remain limited. This multicenter Italian study describes its use in 32 patients with Enterobacterales infections, including urinary tract, bloodstream, and respiratory infections. Clinical cure was achieved in all patients, microbiological eradication was documented in most cases, and no in-hospital deaths occurred. These findings suggest that cefepime/enmetazobactam may be a useful and well-tolerated carbapenem-sparing option for selected resistant gram-negative infections, while emphasizing the need for larger studies to confirm its role in routine clinical practice.

Pulmonary infection caused by Mycobacterium abscessus is rare in children without underlying pulmonary disease, especially in infants. A 3-month-old female infant was admitted to the Third Xiangya Hospital of Central South University on July 29, 2023. Cough was her only clinical manifestation, and chest computed tomography revealed multiple patchy and mass-like high-density opacities in both lungs. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid confirmed the diagnosis of Mycobacterium abscessus pulmonary disease. Further evaluation for immunodeficiency and whole-exome sequencing revealed no abnormalities. The patient improved after combination therapy with amikacin, cefoxitin, linezolid, and azithromycin, without adverse reactions. For rare pulmonary infections in infants with atypical clinical manifestations and a low positivity rate of conventional etiological tests, metagenomic next-generation sequencing may facilitate early diagnosis.