Multicenter Observational Study Research Articles

Impact of postoperative radiography on the management of humeral condylar fractures in immature dogs.

To evaluate the impact of postoperative radiographs on treatment decisions for skeletally immature dogs undergoing repair of a fractured humeral condyle. Retrospective observational multicenter study. A total of 139 dogs (<12 months of age). Medical records of dogs who underwent humeral condylar fracture repair were retrieved and analyzed. Data collected included dog's signalment, fixation method, reported client's concerns, follow-up clinical examination findings, radiographic assessment, and any documented changes to the postoperative plan. Out of the 139 cases, 23 dogs (17%) required a change in their postoperative plan. Owner concerns (OR: 7.6), prolonged use of analgesic drugs (OR: 7.9), presence of lameness (OR: 5.9), abnormal clinical findings at the time of follow-up examination (OR: 44.8) and radiographic abnormalities (OR: 51.9) significantly increased the likelihood of a change in the postoperative plan. Most importantly, none of these postoperative plan changes were solely attributed to radiographic abnormalities at the time of the follow-up examination. Follow-up radiographs did not influence the postoperative management plan in cases where clients reported no concerns, the dogs did not require prolonged analgesic treatment, showed no lameness on examination, and had unremarkable clinical findings CLINICAL SIGNIFICANCE: In the absence of client concerns, prolonged use of analgesic drugs, lameness on examination, and clinical abnormalities, the necessity of follow-up radiographs in immature dogs that underwent humeral condylar fracture repair is debatable.

Co-occurrence of frailty, possible sarcopenia, and malnutrition in community-dwelling older outpatients: a multicentre observational study.

The co-occurrence of frailty, sarcopenia and malnutrition has been well studied in inpatient and nursing home settings, which are associated with a higher risk of all-cause mortality. However, multicentre data from community-dwelling outpatient settings are lacking. Therefore, we aimed to find the prevalence of frailty, possible sarcopenia and malnutrition, their overlap, and the associated factors in community-dwelling older outpatients. We collected data from community-dwelling outpatients aged 60 years in Indonesian geriatric care centres to conduct this cross-sectional study with bivariate and multivariable analyses. Frailty, possible sarcopenia and malnutrition diagnoses were based on the FRAIL scale, AWGS 2019 consensus and MNA-SF, respectively. The prevalence of frailty, possible sarcopenia and malnutrition in community-dwelling older outpatients was 13.6%, 45.5% and 5.3%, respectively, while the prevalence of their co-occurrence was 3.3%. The prevalence was associated with transient ischaemic attack (TIA) and cerebrovascular accident (OR, 5.53; 95% CI: 1.48-20.61), cognitive impairment (OR, 3.70; 95% CI: 1.21-11.31), and dependent functional capacity (OR, 11.62; 95% CI: 3.38-39.99). The three evaluated syndromes were found to overlap in 24.1%, 7.2% and 61.3% of subjects with frailty, possible sarcopenia and malnutrition, respectively. Of these subjects, a substantial proportion were female or had low educational attainment, diabetes mellitus, hypertension, cognitive impairment, multimorbidity or dependent functional status. Approximately 1 in 30 community-dwelling older outpatients had overlapping frailty, possible sarcopenia and malnutrition. The condition is associated with TIA and cerebrovascular accident, cognitive impairment and dependent functional capacity. Standardized screening in community-dwelling older population is necessary.

Left atrial appendage occlusion in patients with atrial fibrillation and intracerebral haemorrhage associated with cerebral amyloid angiopathy: a multicentre observational study and pooled analysis of published studies

BackgroundCerebral amyloid angiopathy (CAA) is a common cause of intracerebral haemorrhage (ICH) with a high recurrence risk. Left atrial appendage occlusion (LAAO) is a method for ischaemic stroke prevention in...

Radiotherapy & total neoadjuvant therapy for recurrent rectal cancer in previously irradiated patients, (RETRY): a multicenter prospective observational study

BackgroundLocal recurrence of rectal cancer (LRRC) previously treated with radiotherapy is associated with a poor prognosis. Historically, the integration of radiotherapy (RT) with surgery has improved the likelihood of complete resections (R0) and, consequently, enhanced survival. Unfortunately, many LRRC cases are not amenable to surgical intervention. The inclusion of chemotherapy (CHT) alongside advanced RT techniques including proton and carbon ion RT (CIRT) and stereotactic body radiation therapy (SBRT), has generated new treatment options. Therefore, there is a need for improved stratification of LRRC patients to enhance treatment outcomes. The RETRY is an integrated trial with the primary aim to explore if combining CHT with RT in all available modalities can enhance local control (LC) in LRRC patients, consequently improving survival.MethodsExperts from Italian centers specializing in rectal cancer and LRRC management collaborated to design a prospective multicenter observational study within the AIRO group for gastrointestinal malignancies. Eligible participants are adult LRRC patients who previously had pelvic RT, meet specific criteria, and are affiliated with the participating Italian centers. Specific criteria must be met for CIRT referral. A total of 88 patients will be enrolled over three years. The primary objective is to determine the 3-year LC rate. Secondary outcomes include assessing survival, quality of life, and R0 resection rates in surgery cases. A minimum dose of 40 Gy, conventional fractionation with concomitant fluoropyrimidine—with/without oxaliplatin-based CHT (CRT) is prescribed in neoadjuvant setting. Alternatively, the dose will vary from 35 to 40 Gy in 5 fractions based on clinical judgment, by SBRT. Both proton and photon therapies will be evaluated in these approaches. Surgery will be considered if deemed operable. In inoperable cases, CIRT with a dose of 40–60 Gy relative biological effectiveness (RBE) will be administered with a daily dose fraction ranging between 3 and 4.8 Gy RBE.DiscussionThe RETRY trial aims to investigate the combined effects of RT and CHT and when feasible the addition of surgery, to determine whether this comprehensive approach can result in improved survival and quality of life for LRRC patients.Trial registration number ClinicalTrials.gov (No. NCT05984576).

Update to: Study Pre-protocol for “BronchStart - The Impact of the COVID-19 Pandemic on the Timing, Age and Severity of Respiratory Syncytial Virus (RSV) Emergency Presentations; a Multi-Centre Prospective Observational Cohort Study”

Background In 2021 we launched the BronchStart study, which collected information on 17,899 presentations in children with serious respiratory tract infections following the release of lockdown restrictions. Our study informed the Joint Committee on Vaccination and Immunisation’s decision to recommend the introduction maternal respiratory syncytial virus (RSV) vaccination, which was introduced in the United Kingdom in August/September 2024. Study question We modified our original protocol to conduct a United Kingdom-wide assessment of maternal vaccination against RSV. Methods and likely impact We will conduct a multi-centre study, utilising the PERUKI network used in the original BronchStart study, to assess the effectiveness of maternal vaccination using a test-negative study design. We will gather detailed clinical information on children admitted with bronchiolitis in the post-RSV vaccination era, and understand possible reasons for incomplete vaccine uptake.

Validation of the European Oncology toolkit for the self-assessment of Quality of Life (EUonQoL-Kit) in cancer patients and survivors: study protocol of a pan European survey

BackgroundEuropean cancer programmes and policies lack a unified health-related quality of life (HRQoL) assessment tool. The European oncology quality of life toolkit (EUonQoL-Kit) is a novel set of HRQoL questionnaires, co-designed with cancer patients and survivors, translated and culturally adapted into 31 European languages, and with both static and dynamic electronic administration modes. The main aim of this study is the psychometric assessment of the static version. Secondary aims include evaluating the EUonQoL-Kit acceptability, cross-validating the administration modes, exploring individual factors potentially affecting HRQoL and HRQoL inequalities between countries.MethodsA sample of 4,500 participants, including three groups (active treatment, survivors, and palliative care) from 45 centres in 25 EU Member States and 7 associated countries, will be enrolled in a multicentre observational cross-sectional study. All participants will complete the static EUonQoL-Kit; three subsamples (each 10% of the total sample) will also respectively complete the following: a) dynamic EUonQoL-Kit, based on Item Response Theory (IRT)/Computer Adaptive Testing (CAT), b) FACT-G and EQ-5L-5D, and c) static EUonQoL-Kit (re-test). Psychometric analyses will encompass exploratory and confirmatory factor analyses (measurement model and structural validity), Cronbach's alpha (internal consistency), intraclass correlation coefficient (test–retest reliability), Pearson/Spearman correlation (concurrent validity), comparison of group scores (construct validity), and Differential Item Functioning (cross-country item equivalence). Secondary analyses will evaluate participant response time and rate, and static/dynamic score differences. Regression models will estimate associations between individual factors and HRQoL.DiscussionThe EUonQoL-Kit will serve to systematically incorporate patient perspectives into European cancer policies and to address HRQoL inequalities across Europe.Trial registrationClinicalTrials.gov Identifier: NCT05947903, 2023–06-28.

Routine preoperative blood group and save is unnecessary for adult emergency appendicectomies: A retrospective multicentre study.

Routine group and save (G&S) is commonly performed before appendicectomy despite limited evidence. This study aims to evaluate the necessity of preoperative G&S by determining perioperative blood transfusion rates. A multicentre retrospective observational study of adult patients who had emergency appendicectomy across four hospitals between August 2018 and November 2020. Data analysed included demographics, operative details, G&S, crossmatching and perioperative blood transfusion. 1105 patients were identified, 635 (57.4%) were male. Median age was 37 years (IQR 26-52). 1012 (91.6%) were ASA 1 or 2. Surgical approach: 890 (80.5%) laparoscopic, 79 (7.1%) converted to open, 119 (10.8%) open and 17 (1.5%) laparotomy. Severity of appendicitis: 804 (72.8%) inflamed, 56 (5.1%) gangrenous, 235 (21.3%) perforated and 10 (0.9%) normal. 921 (83.3%) patients had preoperative G&S. 42 (3.8%) patients also had crossmatch. No patients required blood transfusion in 30 days post appendicectomy. The cost of G&S is estimated to be £40,164 in this cohort. The need for perioperative blood transfusion is rare in patients undergoing appendicectomy. It has a significant cost impact and can cause unnecessary delays. Our study suggests that a routine G&S policy is not necessary, and we suggest a more 'selective' G&S policy.

Fungal infection-related conditions and outcomes in severe COVID-19: a nationwide case-control study

BackgroundFungal infections are significant complications of severe coronavirus disease 2019 (COVID-19). Although various risk factors for poor outcomes in patients with COVID-19 have been identified, clinical and treatment factors associated with fungal infections in patients with severe COVID-19 remain unclear. This study aimed to elucidate clinical factors associated with fungal infections during severe COVID-19 treatment.MethodsThis was a post hoc analysis of the J-RECOVER study, a multicenter retrospective observational study involving patients with COVID-19 who required admission at 66 hospitals between January and September 2020. Inclusion criteria were ages ≥ 18 years, COVID-19 diagnosis with reverse-transcription polymerase chain reaction, and treatment with mechanical ventilation (MV). Patients who received antifungal drugs before MV were excluded. Potential predictors were identified through univariate analysis of patient and treatment characteristics between patients with- and those without fungal infection, which was defined as antifungal agent use for ≥ 5 days. To account for facility-specific data clustering, generalized estimating equations (GEE) were employed as adjusted analyses to calculate the relative risks of potentially associated factors. Two sensitivity analyses were performed with modified definitions for the two groups: patients who received antifungal drugs for ≤ 4 days were excluded, and fungal infection was re-defined as antifungal drug use for ≥ 14 days.ResultsAmong 4,915 patients in the J-RECOVER study, 559 adults with COVID-19 who required MV were included. Fungal infections occurred in 57 (10.2%) patients. Univariate analyses identified age, age ≥ 65 years, D-dimer level, remdesivir use, steroid use, and duration of steroid therapy as potential predictors of fungal infections. Multivariate analysis using GEE on these six factors revealed that only the duration of steroid use was significantly associated with an increased risk of fungal infection (odds ratio [OR] for a day increase: 1.01; 95% confidence interval [CI]: 1.00–1.01; p < 0.001). The two sensitivity analyses similarly showed that the duration of steroid use was associated with fungal infection (odds ratio for a day increase: 1.01; 95% CI: 1.00–1.01; p < 0.001 for both).ConclusionsIn patients with severe COVID-19 requiring MV, each additional day of steroid use was associated with prolonged use of antifungal medications for ≥ 5 days.

How low can you go? Antibiotic use in Swedish dogs with gastroenteritis

BackgroundCanine gastroenteritis (CGE) is a common cause for seeking veterinary care in companion animal medicine and an area where antibiotics have been reported to be widely used. Therefore, creating relevant benchmarks for antibiotic use in CGE is important when implementing and analyzing antibiotic stewardship interventions. The aim of this paper was to describe the level and temporal trend of systemic antibiotic use for CGE in Sweden between 2020 and 2023.Materials and methodsThis was an observational multicenter cohort study. Retrospective data from 93,641 CGE consultations was extracted from the electronic health record and analyzed. All CGE consultations were included irrespective of age, breed, severity of disease and level of care. To evaluate the data, 100 medical records of CGE consultations were also manually reviewed using a predefined study protocol.ResultsThe overall level of systemic antibiotic use in Swedish dogs diagnosed with gastroenteritis was 5.7% during the study period, with aminopenicillins being the most abundantly used antibiotics (60.2%). The yearly level of antibiotic use in CGE declined from 8.1% in 2020 to 3.9% in 2023, with a statistically significant annual percentage change (APC) of −21.3% (95% CI, −22.8 to −19.7). Concurrently, the annual all-cause mortality decreased for all CGE consultations. Higher levels of antibiotic use were seen in hospitalized CGE (21.7% compared to 2.1% for non-hospitalized CGE, OR 13.1, 95% CI: 12.3–14.0, p &amp;lt; 0.001) and hemorrhagic diarrhetic CGE (21.0% compared to 5.5% for non-hemorrhagic diarrhetic CGE, OR 4.6, 95% CI: 4.2–4.9, p &amp;lt; 0.001).ConclusionThis study revealed a low level and a significantly declining trend of antibiotic use in canine gastroenteritis in Sweden, implicating a high level of awareness and compliance to antibiotic guidelines among Swedish veterinarians. During the same period, the all-cause mortality rates decreased significantly for all CGE consultations, implicating that this level of antibiotic use do not compromise patient safety. Benefiting from automatic surveillance, we hereby provide important benchmarks which should encourage more prudent use of antibiotics in CGE internationally.

Coffee consumption and adverse cardiovascular events in patients with atrial fibrillation

BackgroundThere is some evidence of reduced major cardiovascular event (MACE) rates associated with moderate coffee consumption in the general population. However, there is concern about the potential risks of coffee consumption in patients with atrial fibrillation (AF). Therefore, we aimed to investigate the association between coffee consumption and MACE in AF patients.MethodsData of patients with documented AF enrolled in two large prospective observational multicenter cohort studies (Swiss-AF and Beat-AF) were analyzed. Follow-up information was obtained on a yearly basis. Coffee consumption was categorized into two main groups: “daily” and “not-daily” coffee consumers as well as additional subcategories. The primary endpoint was MACE, defined as a composite of stroke or systemic embolism, myocardial infarction, hospitalization for acute heart failure, and cardiovascular mortality. Secondary endpoints were the individual components of MACE and all-cause mortality. We performed time-updated multivariable adjusted Cox regression analyses to investigate the association between coffee consumption and MACE.ResultsThe incidence rate for MACE was 5.09 per 100 person-years (py) in daily and 7.49 per 100 py in not-daily consumers (median follow-up duration: 4.7 years). After adjustment for pre-selected confounding variables, daily coffee consumption was associated with a 23% lower hazard for MACE compared to not-daily consumption (hazard ratio (HR) (95% confidence interval (CI)) 0.77 (0.66; 0.89)). Patients with moderate coffee consumption (2–3 cups/day) had the lowest hazard for MACE compared to patients with not-daily coffee consumption (HR (95% CI) 0.74 (0.63; 0.87)).ConclusionsIn a population of AF patients, daily coffee consumption was associated with a reduced risk for MACE, hospitalization for acute heart failure, and all-cause mortality. The results were inconclusive for stroke or systemic embolism, myocardial infarction, and cardiovascular death. In this analysis, we found no evidence of an unfavourable association of daily coffee consumption in AF Patients with adverse outcome events.Trial registrationClinicalTrials.gov Identifier: NCT02105844.

Antidepressant and anxiolytic efficacy and tolerability of agomelatine in the treatment of depression after COVID-19 in daily clinical practice (non-interventional study TELESPHOR)

Depression and anxiety are among the most common disorders observed in patients after COVID-19 coronavirus infection.Objective: to evaluate the antidepressant efficacy and tolerability of agomelatine in patients with a depressive episode (DE) after COVID-19 infection in everyday clinical practice.Material and methods. The multicenter observational study TELESPHOR included outpatients aged 18 to 65 years who developed DE (Hamilton Depression Rating Scale (HAMD-17) score of 8–24) within 3 months of the resolution of a laboratory-confirmed COVID-19 infection and started monotherapy with agomelatine. Patients were assessed at enrolment and subsequently at weeks 2, 4 and 8 of the observation period. The primary endpoint was the change in HAMD-17 scores by week 8 of the observation in patients taking agomelatine as an antidepressant. The main secondary outcome variables were the dynamics of scores for items 10 (psychic anxiety) and 11 (somatic anxiety) of the HAMD-17 scale, the proportion of responders and remitters (according to the HAMD-17 scale) and the impact on quality of life (QOL) according to the SF-36 questionnaire. The tolerability of agomelatine was assessed at each visit. Data from all patients who participated in the study and took agomelatine at least once were included in the efficacy and safety analysis. The final analysis included data from 103 patients, including 73 women (70.9%).Results. Treatment with agomelatine was associated with a significant improvement in depression severity: the mean HAMD-17 total score decreased statistically significantly at weeks 2, 4 and 8 from 16.3±4.7 at study inclusion to 13.7±4.5, 9.5±4.9 and 5.4±3.6 points – by 2.6±3.3, 6.7±5.3 and 10.9±4.9 points, respectively, compared to baseline (p&lt;0.0001 for all time points). The average score for item 10 (psychic anxiety) and item 11 (somatic anxiety) of the HAMD-17 scale also decreased significantly from 1.4±0.9 and 1.3±0.8 at baseline to 0.5±0.6 and 0.6±0.6 points by the eighth week of observation (p&lt;0.0001). The indicators of the scales for physical functioning and mental health of the SF-36 questionnaire improved significantly compared to the initial values – from 39.7±8.4 to 50.5±5.7 points (p&lt;0.0001) and from 37.3±8.6 to 58.7±6.9 points (p&lt;0.0001) respectively, by the eighth week. The proportion of responders was 81.4 %, the proportion of remitters was 71.6%. Agomelatine was well tolerated during the entire observation period. No adverse events were recorded that led to discontinuation of the drug. One patient showed inefficacy of the treatment, so he discontinued participation in the study.Conclusion. The treatment of patients with DE after COVID-19 with agomelatine is characterized by significant antidepressant and anxiolytic efficacy, improved QOL and good tolerability.

Electroconvulsive therapy-specific volume changes in nuclei of the amygdala and their relationship to long-term anxiety improvement in depression.

Electroconvulsive therapy (ECT) is one of the most effective treatments for depression. ECT induces volume changes in the amygdala, a key center of anxiety. However, the clinical relevance of ECT-induced changes in amygdala volume remains uncertain. We hypothesized that nuclei-specific amygdala volumes and anxiety symptoms in depression could explain the clinical correlates of ECT-induced volume changes. To test this hypothesis, we enrolled patients with depression who underwent ECT (N = 20) in this multicenter observational study and collected MRI data at three time points: before and after treatment and a 6-month follow-up. Patients who received medication (N = 52), cognitive behavioral therapy (N = 63), or transcranial magnetic stimulation (N = 20), and healthy participants (N = 147) were included for comparison. Amygdala nuclei were identified using FreeSurfer and clustered into three subdivisions to enhance reliability and interpretability. Anxiety symptoms were quantified using the anxiety factor scores derived from the Hamilton Depression Rating Scale. Before treatment, basolateral and basomedial subdivisions of the right amygdala were smaller than those of healthy controls. The volumes of the amygdala subdivisions increased after ECT and decreased during the follow-up period, but the volumes at 6-month follow-up were larger than those observed before treatment. These volume changes were specific to ECT. Long-term volume changes in the right basomedial amygdala correlated with improvements in anxiety symptoms. Baseline volumes in the right basolateral amygdala correlated with long-term improvements in anxiety symptoms. These findings demonstrate that clinical correlates of ECT-induced amygdala volume changes are existent, but in a nucleus and symptom-specific manner.

A Multicenter Prospective Cohort Study of Antibiotics for OnabotulinumtoxinA.

Urinary tract infection (UTI) is the most common complication of intradetrusor onabotulinumtoxinA (BTX-A) injection. Despite this, there are no evidence-based guidelines on antibiotic prophylaxis. Our primary aim was to determine whether antibiotic prophylaxis decreased symptomatic, culture-proven UTI rates within 6 weeks of intradetrusor BTX-A injection. Our secondary aims were to determine if there are differences between antibiotic regimens and to identify risk factors for developing a UTI. This was a prospective, observational multicenter cohort study of female patients receiving BTX-A for idiopathic overactive bladder. We compared patients who received antibiotics (nitrofurantoin or trimethoprim-sulfamethoxazole) to those who did not. To detect a 15% difference in UTI rates between groups (80% power, alpha = 0.05), 270 participants were needed. A total of 282 participants ultimately received BTX-A and were included in the analysis. One hundred eighty-one (62.6%) were in the antibiotic cohort and 101 (35.8%) were in the no-antibiotic cohort. The overall rate of symptomatic, culture-proven UTI was 12.1%, and there was no difference between the antibiotic and no-antibiotic cohort (10.6% vs 14.9%, respectively; P = 0.29). On multivariable logistic regression, UTI was associated with older age (adjusted odds ratio [aOR], 1.07; 95% CI, 1.02-1.11), BTX-A dose of 200 units (aOR, 4.24; 95% CI, 1.45-12.35), and self-catheterization (aOR, 26.0; 95% CI, 3.62-186.5). The odds of symptomatic UTI were lower among postmenopausal participants (aOR, 0.13; 95% CI, 0.02-0.68) and participants in the Northeast United States (aOR, 0.23; 95% CI, 0.08-0.72). Our study did not find a lower rate of symptomatic, culture-proven UTI among participants who took antibiotics compared with those who did not.

Epidemiology and Impact of Social Hardships in Children With Multiple Sclerosis in the United States.

Social determinants of health (SDOH) affect patient health outcomes, but the impact on patients with pediatric-onset multiple sclerosis (POMS) has not been well studied. Study objectives were to (1) describe the frequency of adverse SDOH, (2) evaluate social hardships as a potential barrier to the initiation of disease-modifying therapy (DMT), and (3) explore the association between adverse SDOH and disease outcomes in POMS, as well as study attrition. This was a retrospective multicenter observational study conducted through the United States Network of Pediatric MS Centers database. Participants were patients diagnosed with POMS (excluding primary progressive MS). The primary outcome was time to initiation of DMT. Secondary outcomes included most recent Expanded Disability Status Scale (EDSS) score, steroid treatment for the first event, time to second event, and study attrition. Demographic variables and clinical outcomes were compared between patients with and without hardships (maternal education of high school or less, public insurance/no insurance, or single/no-income household). Multivariable regression models were used to assess the impact of social hardship on study outcomes. There were 996 total participants (69% female, mean age at symptom onset and EDSS score [±SD] were 14.2 ± 3 and 1.2 ± 1.1, respectively). Of 768 patients with complete demographic information, 66% reported a hardship. Hardship was associated with younger age at symptom onset and diagnosis. While there was no difference in time to DMT initiation, patients with hardship were more likely to receive steroids for the first event (odds ratio [OR] 1.66, 95% CI 1.21-2.26, p = 0.002). Lack of private insurance was associated with increased risk of study attrition (OR 1.85, 95% CI 1.14-3.00, p = 0.012) and higher EDSS score (β = 0.15, 95% CI 0.01, 0.28). Living in a no-income household (vs dual-income) was associated with a shorter time to second event (hazard ratio 1.33, 95% CI 1.02-1.74, p = 0.034). The experience of hardships is common and associated with younger age at symptom onset and diagnosis, as well as shorter time to second event. Lack of private insurance is associated with study attrition and a higher EDSS score despite no difference in time to initiating DMT. There may be differences in early disease pathophysiology related to social hardship, and future studies are needed to better understand this complex relationship.

Transseptal Sheath Perfused with High Concentration Heparinized Saline for Reducing Sheath-associated Thrombus.

Transseptal catheterization is critical for atrial fibrillation (AF) ablation but risks thromboembolism. Transseptal sheaths (TSS) were suggested for continuous heparinized saline solution flush. The safety and effectiveness of a simple TSS management to reduce sheath-associated thrombus development risk was investigated. AF patients who underwent radiofrequency ablation with the simple TSS management were studied under a retrospective multi-center observation study and a prospective single-center observation study. TSS and dilators were washed and perfused with high concentration heparinized saline (20u/mL). Immediately after two successful transseptal punctures, activated clotting time ≥300s was maintained by heparin infusion. TSS aspiration with negative suction and re-perfusion with high concentration heparinized saline (20u/mL) was performed for the remaining procedure before and after catheter withdrawal. A total of 4765 AF patients underwent 5367 ablation procedures were enrolled in the retrospective study, involving 156 (2.9% per procedure) complications. No acute stroke occurred during all the procedures. Perioperative thromboembolic complications occurred in 10 (0.21%) patients and in 10 (0.19%) procedures. Thromboembolic complications occurred within 24 h, between 24-48 h, and after 48 h post-procedure in six, two, and two patients, respectively. In the prospective observation study, neither sheath- nor catheter-associated thrombus were detected by the intracardiac echocardiography during all 127 procedures, without any perioperative thromboembolic complications. No hemorrhagic cerebrovascular complication was encountered in both observational studies. For AF radiofrequency ablation, it was safe and effective for TSS high concentration heparinized saline infusion only. This approach could avoid sheath-associated thrombus for interventional procedures.

Hierarchically Positioning Laparoscopic Microwave Ablation in the Therapeutic Span of Early Hepatocellular Carcinoma: A Real-Life Comparative Analysis.

Laparoscopic microwave ablation (LMWA) has yet to gain a specific place in treatment guidelines for early hepatocellular carcinoma (HCC). This study compared the outcomes of LMWA and trans-arterial chemoembolization (TACE) for early non-resectable patients with HCC, taking percutaneous radiofrequency ablation (PRFA) as the reference treatment. A retrospective multicenter observational study was conducted, enrolling non-transplantable, non-resectable patients who had early HCC treated with LMWA (n = 658) from Padua and Milan centers, and with PRFA (n = 844), and TACE (n = 425) from the ITA.LI.CA multicenter database. The matching-adjusted indirect comparison (MAIC) method was used to obtain weighted LMWA and TACE populations similar to the reference PRFA population. Laparoscopic ablation showed an excellent safety profile, and MAIC-weighted early postoperative deaths were comparable among the groups. The MAIC-weighted overall survival was similar between the LMWA (1-, 3-, and 5year survival of 91.0 %, 67.9 %, 47.0 %, respectively) and PRFA (1-, 3- and 5year survivals of 90.0 %, 64.7 %, 46.6 %, respectively) groups (p = 0.678) and significantly better for the LMWA group than for the TACE group (1-, 3- and 5year survivals of 84.7 %, 48.8 %, 33.6 %, respectively) (p < 0.001). Weighted multivariate overall survival analysis and competing risk/subgroup analyses confirmed the non-inferiority of LMWA to PRFA and its superiority to TACE. The LMWA- and PRFA-treated patients had a significantly lower risk of HCC-related death (p = 0.004) than the TACE-treated patients (p = 0.001). Conversely, the groups did not differ significantly in terms of non-HCC-related deaths. The non-inferiority of LMWA to PRFA, its superiority to TACE, and its applicability to a wide range of presentations with few contraindications support its inclusion among radical therapies for treating early-HCC patients.

Outcomes of pregnant and post-partum patients admitted to the intensive care unit with COVID-19 in Australia: An analysis of SPRINT-SARI Australia.

Pregnant and post-partum (collectively peri-partum) women may be at increased risk of severe COVID-19 disease. To describe the characteristics, interventions, and outcomes of peri-partum patients admitted to intensive care units (ICUs) in Australia with COVID-19. We conducted a prospective, multicentre observational study using the SPRINT-SARI Australia database across 63 ICUs in Australia. All women <45 years of age, admitted to a participating Australian ICU, with laboratory-confirmed COVID-19 between 1 March 2020 and 1 June 2023 were included. Participants were categorised as either peri-partum, defined as pregnant or up to six weeks post-partum, or non-pregnant. The primary outcome was in-hospital mortality. A total of 737 eligible female patients were admitted to ICUs over the study period: 168/737 (23%) were peri-partum, while 569/737 (77%) were non-pregnant. The median age of peri-partum women was 31 (interquartile range (IQR) 27-36) years old, and median gestation was 28.0 (IQR 4-40) weeks. When compared to non-pregnant women, peri-partum women had lower rates of comorbidities (1.8% vs 14.4% P < 0.001), lower vaccination rates (27.4% vs 45.2%, P < 0.001), similar rates of mechanical ventilation, and greater use of tocilizumab (29.2% vs 4.0%, P < 0.001). Complications were low in both groups. In-hospital mortality was lower in peri-partum patients: 1/168 (0.6%) vs 24/569 (4.2%); P = 0.04. Peri-partum patients made up ~25% of all women aged <45 years old admitted to Australian ICUs with COVID-19, and nearly 30% required mechanical ventilation. Despite lower vaccination rates in peri-partum patients, in-hospital mortality was lower than in non-pregnant patients.

Use of the high-flow helmet CPAP non-invasive ventilation device designed in Peru in patients with severe acute respiratory syndrome (COVID-19): A prospective multicenter study

High-flow non-invasive ventilation (NIV) devices reduce the morbidity and mortality of COVID-19. The objective was to evaluate the use of the non-invasive ventilation device with high-flow helmet CPAP designed in Peru in patients with severe acute respiratory syndrome (COVID-19) hospitalized in the emergency services of five hospitals. Prospective multicenter and cross-sectional observational study from five hospitals from July to August 2020. 19 patients were recruited and divided into two groups (G-1 n = 10; G-2 n = 9) applying clinical and gasometric parameters as indicators of disease evolution upon hospital admission and within 24 hours. A progressive increase in these parameters was observed in those patients who used the NIVCPAP helmet within the first 24 hours. In G-01, improvement was evident in 90% (n = 9/10): PaO2 (range 48–137; average: 82.49 ± 8.07; p-value = 0.008), CO2 (25.2–51.0; 36.62 ± 2.62; p-value p = 0.327), and the PaO2/FiO2 coefficient (87–318; 191.5 ± 18.68). 10% of patients did not progress optimally, being subjected to endotracheal intubation and invasive mechanical ventilation. In G-02 the values ​​were %SatO2 (range 92–98; 96 ± 0.76) and the SaO2/FiO2 coefficient (214–228; 223.2 ± 1.80), indicating significant improvement within 24 hours (p &amp;lt; 0.001). It is concluded that the use of the CPAP helmet non-invasive ventilation (NIV) device contributes to improving gasometric values ​​and clinical condition. Being an alternative to recover typical cases of COVID-19 in all hospitals in Peru.

Methods of nivolumab administration in advanced melanoma: A comparison of patients' clinical outcomes treated with flat dose or weight-adjusted dose, a multicenter observational study.

Nivolumab obtained approval in advanced melanoma (AM) with weight-adjusted dose (WAD) administration (3 mg/kg/2 weeks). In 2018, the dosage regimen was changed to flat dose (FD) administration (240 mg/2 weeks or 480 mg/4 weeks) based on a modeling study, without clinical data. AM patients have been prospectively included in the French national multicenter MelBase database since 2013. First-line patients treated with nivolumab monotherapy were included in the WAD or FD groups of this study. The primary end point was the incidence of grade ≥3 immune-related adverse events (irAEs). Secondary end points were incidence of any grade irAEs, and overall survival (OS) and progression-free survival (PFS). Inverse probability of treatment weighting was used to balance groups on their baseline characteristics. Between 2015 and 2022, 348 patients were included: 160 in the WAD and 188 in the FD groups. In the FD group, 45% and 27% of patients weighed <75 kg and >85 kg, respectively. Grade ≥3 and any grade irAEs rates were 13.1% versus 11.7% (p=.8) and 63.1% versus 67.0% (p=.5) in the WAD and FD groups, respectively. After weighting, median PFS was 3.1 and 3.7 months (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.65-1.07), and median OS was 24.8 and 37.0 months (HR, 0.74; 95% CI, 0.54-1.01) in the WAD and FD groups, respectively. There was no difference in the incidence of severe irAEs and in median PFS between AM patients treated by WAD or FD nivolumab. The median OS between patient groups did not reach statistical significance.

Real-World Study of EGFR-TKI Rechallenge With Another TKI After First-Line Osimertinib Discontinuation in Patients With EGFR-Mutated Non-Small Cell Lung Cancer: A Subset Analysis of the Reiwa Study.

First-line osimertinib is widely used to treat patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancers (NSCLC). In clinical practice, rechallenge therapy with another EGFR-tyrosine kinase inhibitor (TKI) is often performed after first-line TKI discontinuation owing to resistance or toxicity; however, the efficacy and toxicity of EGFR-TKI rechallenge after first-line osimertinib have not been adequately investigated. This study aimed to examine the efficacy and safety of EGFR-TKI rechallenge with another TKI. This multicenter prospective observational study enrolled patients with EGFR-mutated NSCLC who received first-line osimertinib and another EGFR-TKI as second- or third-line treatment between September 2018 and August 2020. Fifty-three patients received rechallenge with another EGFR-TKI in the second-line (n = 38, 71.7%) or third-line (n = 15, 28.3%) setting. The primary reason for first-line osimertinib discontinuation was toxicity in 32 (60.4%, 17 patients with pneumonitis) and disease progression in 20 (37.7%) patients. The most common rechallenge EGFR-TKI was afatinib (n = 24, 45.3%), followed by gefitinib (n = 16, 30.2%) and erlotinib (n = 8, 15.1%). The real-world time to treatment failure (rwTTF) was 7.3 months. The rwTTF for the toxicity discontinuation and progressive disease discontinuation groups was 9.3 months and 5.1 months, respectively, (HR 1.61, p = 0.119). EGFR-TKI rechallenge was discontinued due to toxicity in nine patients (17.0%), but no patient developed pneumonitis. EGFR-TKI rechallenge with another TKI is well tolerated in patients with EGFR-mutated NSCLC. Thus, it may be a useful treatment option after first-line osimertinib failure, especially after osimertinib discontinuation due to toxicity.