Multicenter Observational Study Research Articles

Management challenges and the role of adjuvant chemotherapy in remnant gastric cancer: an analysis of 313 patients from the KEGG multicenter observational study.

Clinical findings and postoperative follow-up data on remnant gastric cancer (RGC) are limited due to its rarity. Additionally, the preoperative staging, radical surgery, and managing recurrence in RGC present significant clinical challenges. We analyzed the clinicopathological findings, adjuvant chemotherapy, and patterns of postoperative recurrence of 313 consecutive patients who underwent curative surgery for RGC at 17 Japanese institutions. This study investigated the optimal management of RGC and the impact of adjuvant chemotherapy (AC) on recurrence-free survival (RFS). Pathological stages I, II, and III were observed in 55.9% (N = 175), 24.9% (N = 78), and 19.2% (N = 60) of the patients, respectively. The overall concordance rate between clinical and pathological T staging was 58.3%, with a clinical T4 sensitivity of 41.4% for diagnosing pathological T4. During the median follow-up period of 4.6years, disease recurrence occurred in 24.3% of patients. Most recurrences (over 80%) occurred within 2.5years, and 96.1% within 5years after RGC surgery. Peritoneal recurrence was the most common in patients with advanced RGC, accounting for 14.1% in stage II and 28.3% in stage III. Multivariable regression analysis showed that AC was significantly associated with a longer RFS, with a hazard ratio of 0.45 (95% confidence interval: 0.26-0.76). Our study underscores the importance of early detection, accurate preoperative staging, and postoperative surveillance in managing advanced RGC cases. Despite some limitations, our findings indicate that AC may provide survival benefits comparable to those seen in primary gastric cancer.

Prescriptions of anti-reflux drugs in neonatology and neonatal intensive care units: A large multicentre observational study (2014-2022).

Gastro-oesophageal reflux is common in newborns, especially in premature infants. Treatment by medication is controversial as the drugs prescribed have not been consistently proven to be effective and are known to have adverse effects. This study sought to identify trends in the prescription of anti-reflux medication in a large group of French neonatal units. Data on prescriptions of anti-reflux treatments-proton pump inhibitors (PPIs), antacids, histamine-2 receptor antagonists (H2RAs), and prokinetics-from 2014 to 2022 for infants with a corrected gestational age <45 weeks, were extracted from a prescription database (Logipren®) used by 63 French neonatal units, and then analysed. Of all infants recorded in the database during the study period (n =152 743), 10.2% (n = 15 650) were prescribed anti-reflux medication (95% confidence interval [CI] 10.0-10.4%), mainly as monotherapy (77.5%). The rate was higher in the subgroup of preterm infants born before 28 weeks of gestation (n = 9493) (20.6%, 95% CI 19.8-21.4%; n = 1956). PPIs were the most commonly prescribed anti-reflux medications (6.9% of infants, 95% CI 6.8-7.0), followed by antacids (5.2%, 95% CI 5.1-5.3%), while H2RAs and prokinetics were rarely prescribed. Over the period, the prescription rate remained stable for PPIs, decreased for H2RAs (τ = -0.86, P = .02), and, among preterm infants born at gestational ages of 28-31 or 32-36 weeks, increased for antacids. Anti-reflux medications were frequently prescribed by neonatal units, especially for extremely premature infants. Most of these prescriptions were for PPIs and antacids.

Neurologic complications in patients receiving aortic versus subclavian versus femoral arterial cannulation for post-cardiotomy extracorporeal life support: results of the PELS observational multicenter study

BackgroundCerebral perfusion may change depending on arterial cannulation site and may affect the incidence of neurologic adverse events in post-cardiotomy extracorporeal life support (ECLS). The current study compares patients' neurologic outcomes with three commonly used arterial cannulation strategies (aortic vs. subclavian/axillary vs. femoral artery) to evaluate if each ECLS configuration is associated with different rates of neurologic complications.MethodsThis retrospective, multicenter (34 centers), observational study included adults requiring post-cardiotomy ECLS between January 2000 and December 2020 present in the Post-Cardiotomy Extracorporeal Life Support (PELS) Study database. Patients with Aortic, Subclavian/Axillary and Femoral cannulation were compared on the incidence of a composite neurological end-point (ischemic stroke, cerebral hemorrhage, brain edema). Secondary outcomes were overall in-hospital mortality, neurologic complications as cause of in-hospital death, and post-operative minor neurologic complications (seizures). Association between cannulation and neurological outcomes were investigated through linear mixed-effects models.ResultsThis study included 1897 patients comprising 26.5% Aortic (n = 503), 20.9% Subclavian/Axillary (n = 397) and 52.6% Femoral (n = 997) cannulations. The Subclavian/Axillary group featured a more frequent history of hypertension, smoking, diabetes, previous myocardial infarction, dialysis, peripheral artery disease and previous stroke. Neuro-monitoring was used infrequently in all groups. Major neurologic complications were more frequent in Subclavian/Axillary (Aortic: n = 79, 15.8%; Subclavian/Axillary: n = 78, 19.6%; Femoral: n = 118, 11.9%; p < 0.001) also after mixed-effects model adjustment (OR 1.53 [95% CI 1.02–2.31], p = 0.041). Seizures were more common in Subclavian/Axillary (n = 13, 3.4%) than Aortic (n = 9, 1.8%) and Femoral cannulation (n = 12, 1.3%, p = 0.036). In-hospital mortality was higher after Aortic cannulation (Aortic: n = 344, 68.4%, Subclavian/Axillary: n = 223, 56.2%, Femoral: n = 587, 58.9%, p < 0.001), as shown by Kaplan–Meier curves. Anyhow, neurologic cause of death (Aortic: n = 12, 3.9%, Subclavian/Axillary: n = 14, 6.6%, Femoral: n = 28, 5.0%, p = 0.433) was similar.ConclusionsIn this analysis of the PELS Study, Subclavian/Axillary cannulation was associated with higher rates of major neurologic complications and seizures. In-hospital mortality was higher after Aortic cannulation, despite no significant differences in incidence of neurological cause of death in these patients. These results encourage vigilance for neurologic complications and neuromonitoring use in patients on ECLS, especially with Subclavian/Axillary cannulation.Graphical abstract

Assessing triage efficiency in Italy: a comparative study using simulated cases among nurses.

Emergency Departments (EDs) across Italy use different triage systems, which vary from region to region. This study aimed to assess whether nurses working in different EDs assign triage codes in a similar and standardized manner. A multicenter observational simulation study involved the EDs of Bolzano Hospital, Merano Hospital, Pisa University Hospital, and Rovereto Hospital. All participating nurses were given 30 simulated clinical cases (vignettes) and asked to assign triage codes according to the triage systems used in their EDs. Subsequently, we assessed inter-rater agreement and evaluated if code assignment had different performance among hospitals in relation to different clinical outcomes. Eighty-seven nurses participated in this study. There was marked variation in assigned triage codes both across hospitals and among individual operators. The kappa values for inter-rater agreement were 0.632 for Bolzano Hospital, 0.589 for Merano Hospital, 0.464 for Pisa University Hospital, and 0.574 for Rovereto Hospital. Sensitivity and specificity levels varied considerably for the same outcomes when comparing different hospitals. There is a high degree of subjectivity in triage code assignment by ED nurses. In the interest of equitable care for patients, this variability within the same country is hardly acceptable.

Outcomes of patients admitted with malignant small bowel obstruction: a subgroup multicentre observational cohort analysis

Introduction and purpose of the studySmall bowel obstruction (SBO) accounts for a substantial proportion of emergency surgical admissions. Malignancy is a common cause of obstruction, either due to a primary tumour or intra-abdominal metastases. However, little is known regarding the current treatment or outcomes of patients with malignant SBO. This study aimed to characterise the treatment of malignant SBO and identify areas for potential improvement and compare overall survival of patients with malignant SBO to patients with non-malignant SBO.Materials and methodsThis was a subgroup analysis of a multicentre observational study of patients admitted with SBO. Details regarding these patients’ diagnoses, treatments, and outcomes up to 1-year after admission were recorded. The primary outcome was overall survival in patients with malignant SBO.ResultsA total of 316 patients with small bowel obstruction were included, of whom 33 (10.4%) had malignant SBO. Out of the 33 patients with malignant SBO, 20 patients (60.6%) were treated with palliative intent although only 7 patients were seen by a palliative team during admission. Nutritional assessments were performed on 12 patients, and 11 of these patients received parenteral nutrition. 23 patients underwent surgery, with the most common surgical interventions being loop ileostomies (9 patients) and gastrointestinal bypasses (9 patients). 4 patients underwent right hemicolectomies, with a primary anastomosis formed and 1 patient had a right hemicolectomy with a terminal ileostomy. Median survival was 114 days, and no difference was seen in survival between patients treated with or without palliative intent.ConclusionMalignant SBO is associated with significant risks of short-term complications and a poor prognosis. Consideration should be given to the early involvement of senior decision-makers upon patient admission is essential for optimal management and setting expectation for a realistic outcome.

Association of serum uric acid to serum creatinine ratio with 1-year stroke outcomes in patients with acute ischemic stroke: A multicenter observational cohort study.

Considering the reliance of serum uric acid (SUA) levels on renal clearance function, its role in stroke outcomes remains controversial. This study investigated the association of renal function-normalized SUA (SUA to serum creatinine ratio, SUA/SCr), a novel renal function index, with the 1-year outcomes in patients with acute ischemic stroke (AIS). This is a prospective, multicenter observational study. Renal function-normalized SUA levels were determined by calculating the ratio of SUA to SCr. One-year outcomes included stroke recurrence, all-cause mortality, and poor prognosis. Multivariable Cox regression analyses and restriction cubic splines for curve fitting were used to evaluate SUA/SCr's association with 1-year stroke outcomes. Among 2294 enrolled patients, after adjustment for potential confounders, multivariable Cox regression analyses showed that each one-unit increase in SUA/SCr corresponded to a 19% decrease in 1-year stroke recurrence in patients with AIS. SUA/SCr was analyzed as a continuous variable and categorized into quartiles (Q1-Q4). Compared with the Q1 reference group, Q2, Q3, and Q4 showed significantly lower 1-year stroke recurrence risks. The trend test indicated significant differences in the 1-year stroke recurrence trend from Q1 to Q4. In these patients, SUA/SCr did not show a significant association with poor prognosis or all-cause mortality. Curve fitting revealed SUA/SCr had a negative but nonlinear association with 1-year stroke recurrence. In patients with AIS, low SUA/SCr may be an independent risk factor for 1-year stroke recurrence. Changes in SUA/SCr had no significant impact on 1-year poor prognosis and all-cause mortality.

Pituitary Apoplexy: a re-appraisal of risk factors and best management strategies in the COVID-19 era.

Pituitary apoplexy (PA) is a clinical syndrome caused by acute hemorrhage and/or infarction of the pituitary gland, most commonly in the setting of a pituitary macroadenoma. PA generally presents with severe headache, nausea, vomiting, visual disturbance, and, in more severe cases, altered mental status. Many factors have been attributed to the risk of developing PA, including most recently, numerous reports showcasing an association with COVID-19 infection or vaccination. Initial management of PA includes evaluation and correction of deficient hormones and electrolytes and an assessment if surgical decompression to relieve pressure on optic nerves and other brain structures is needed. While prompt recognition and treatment are crucial to avoid morbidity and mortality, in the modern era, PA is less commonly considered a true neurosurgical emergency requiring immediate (< 24h) surgical decompression. Traditionally, surgical decompression has been the standard of care for significant mass effects. However, several studies have shown similar outcomes in visual and hormonal recovery with either surgical decompression or conservative medical management. Unfortunately, most evidence on optimal management strategies is limited to retrospective case series, small prospective studies, and one multi-center observational study. This review aims to provide the most up-to-date evidence on the role of COVID-19 in PA and best management strategies.

Phenotyping COVID-19 respiratory failure in spontaneously breathing patients with AI on lung CT-scan

BackgroundAutomated analysis of lung computed tomography (CT) scans may help characterize subphenotypes of acute respiratory illness. We integrated lung CT features measured via deep learning with clinical and laboratory data in spontaneously breathing subjects to enhance the identification of COVID-19 subphenotypes.MethodsThis is a multicenter observational cohort study in spontaneously breathing patients with COVID-19 respiratory failure exposed to early lung CT within 7 days of admission. We explored lung CT images using deep learning approaches to quantitative and qualitative analyses; latent class analysis (LCA) by using clinical, laboratory and lung CT variables; regional differences between subphenotypes following 3D spatial trajectories.ResultsComplete datasets were available in 559 patients. LCA identified two subphenotypes (subphenotype 1 and 2). As compared with subphenotype 2 (n = 403), subphenotype 1 patients (n = 156) were older, had higher inflammatory biomarkers, and were more hypoxemic. Lungs in subphenotype 1 had a higher density gravitational gradient with a greater proportion of consolidated lungs as compared with subphenotype 2. In contrast, subphenotype 2 had a higher density submantellar–hilar gradient with a greater proportion of ground glass opacities as compared with subphenotype 1. Subphenotype 1 showed higher prevalence of comorbidities associated with endothelial dysfunction and higher 90-day mortality than subphenotype 2, even after adjustment for clinically meaningful variables.ConclusionsIntegrating lung-CT data in a LCA allowed us to identify two subphenotypes of COVID-19, with different clinical trajectories. These exploratory findings suggest a role of automated imaging characterization guided by machine learning in subphenotyping patients with respiratory failure.Trial registration: ClinicalTrials.gov Identifier: NCT04395482. Registration date: 19/05/2020.

Clinicopathologic features and new factors affecting constitution of eyelid neoplasms: a 10-year multicentre experience in southern coastal China

BackgroundThis study aims to delineate the key characteristics of eyelid neoplasms in central and southern coastal China and to explore potential factors affecting tumour development. MethodsThis was a retrospective, multicentre observational study. In total, 1302 cases of eyelid neoplasms diagnosed in 2 tertiary hospitals were reviewed from January 2013 to May 2023. Histogenesis, pathologic diagnosis, and potential risk factors were investigated, and the findings were compared with data from various regions and countries. Age- and sex-specific incidence rates, time trends, distributions across age groups, and the relationship with the Sociodemographic Index, latitude, and altitude were calculated. ResultsThere were 1162 benign (89.2%) and 140 malignant (10.8%) cases, representing 63 pathologic types. The median age of benign cases (50 years) was significantly lower than that of malignant cases (72 years) (P < 0.05). The most common benign and malignant lesions were intradermal nevus (28.83%) and basal cell carcinoma (BCC) (74.29%). A relatively younger median age (68 years) for sebaceous gland carcinoma (SGC) was observed, with a male preponderance (sex ratio 2:1). Analyses of the proportions of BCC, SGC, and squamous cell carcinoma in eyelid malignancies revealed significant regression equations (P < 0.05). ConclusionsMost eyelid neoplasms are of epithelial and melanocytic origin, with benign tumours being predominant. The regions with greater Sociodemographic Index exhibit a greater incidence of BCC and a lower incidence of squamous cell carcinoma and SGC. BCC appears to have a greater incidence in regions located at higher latitudes.

Selective opioid agonist Taphalgin® as a component of postoperative analgesia in various surgical areas: “NIKITA” observational multicenter study

Introduction. The role of peptides in antinociceptive system regulation has became a subject of interest for scientists worldwide. The first registered peptide analgesic tyrosyl-D-arginyl-phenylalanyl-glycinamide acetate which currently can be used in clinical practice was developed in Russia under the name Taphalgin® (PharmFirma “Sotex”, Russia). The effectiveness and safety of this pharmaceutical in postoperative pain management was evaluated in the all-Russia multicenter prospective observation program NICITA (Non-interventional Clinical Trial of Taphalgin ®).Aim. To analyze the effectiveness and safety of Taphalgin® in postoperative pain management in various surgical fields.Materials and methods. The observational program NICITA included 887 patients including patients with malignant tumors of various locations from 15 study centers in different Russian cities. All patients underwent surgical interventions in various anatomical areas under general, regional and combination anesthesia. The principal scheme of postoperative pain management was based on the multimodal approach which included peptide opioid agonist alongside acetaminophen, cyclooxygenase inhibitors in combination with regional anesthesia or without it. The study also included patients who underwent small-volume surgeries, and pain was managed through Taphalgin® monotherapy with subsequent switch to cyclooxygenase inhibitors. The primary endpoint of the NICITA observational program was response to therapy after the first Taphalgin® administration. Decreased pain syndrome per the numerical rating scale 15–60 min after subcutaneous injection and maintenance of analgesic effect 3 h later were considered treatment response. The secondary endpoints included mean time to analgesia start after administration of the 1st single drug dose (in min), duration of effect, types and frequency of adverse reactions including serious in the central nervous system, pulmonary system, gastrointestinal tract developed during the observational program, as well as patient and research physician satisfaction with pain management. To evaluate the significance of pain intensity change at rest and in motion in time, analysis of variance with repeat measurements was used; for pairwise comparison of two time periods, Student’s t-test for dependent samples was used. The differences were considered significant at p = 0.05.Results. Statistically significant decrease in pain intensity in the total patient group was observed 15 minutes after Taphalgin® administration; it reached its minimum 40 min after the injection (р &lt;0.05). The percentage of patients responding to analgesic therapy with Taphalgin® was 96.5 %. During administration of the drug, insignificant decrease (10–15 mmHg) in arterial blood pressure (1.7 % of cases) and vertigo (1 % of cases) were observed. In some patients, several adverse reactions were observed. Satisfaction with analgesic effect of Taphalgin® was relatively high both in patients and research physicians.Conclusion. Taphalgin® has pronounced analgesic effect and is effective for pain management after surgical interventions of various volumes and injury level. The use of this drug is associated with low rate of adverse reactions and absence of pulmonary depression characterizing opioid agonists. Therefore, Taphalgin® can be recommended for clinical use for postoperative pain management after various types of surgical interventions.

Subfoveal neurosensory detachment flattening and observe (SNF-Ob) approach for the management of Ci-DMO - a multicentric study.

To understand subfoveal neurosensory detachment flattening and observe (SNF-Ob) strategy and its relationship with visual acuity in the management of centre-involved diabetic macular oedema (Ci-DMO). This was a multicentric retrospective observational study. We reviewed data of 188 eyes of 130 patients who presented with Ci-DMO with subfoveal neurosensory detachment (NSD) and treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents or steroids. The primary outcome was best corrected visual acuity (BCVA) measured at the time of the first subfoveal neurosensory detachment flattening (SNF) and at the end of follow-up. Eyes that achieved 20/50 (LogMAR = 0.40) or better at first SNF had mean LogMAR BCVA 0.38 ± 0.21, 0.24 ± 0.11 and 0.21 ± 0.15 at baseline, at the time of first SNF, and at the end of the last follow-up respectively. Mean LogMAR BCVA significantly improved from baseline to first SNF (p < 0.0001; 95% CI 0.115-0.183) and at the end of the last follow-up (p < 0.0001; 95% CI 0.126-0.213) with a change of Early Treatment Diabetic Retinopathy Study (ETDRS) 10 letters. There was no significant difference in improvement in BCVA from the first SNF and at the end of the last follow-up (p = 0.0781; 95% CI -0.002 to 0.046). Eyes presenting with Ci-DMO and subfoveal NSD are unlikely to improve at SNF with BCVA > 20/50 (LogMAR = 0.40). Further evidence is needed before the combination of good BCVA and SNF may be considered as endpoint of pharmacological therapy for DMO.

Urine Output and Development of Acute Kidney Injury in Sepsis: A Multicenter Observational Study.

Acute kidney injury (AKI) is common in sepsis and a urine output <0.5 mL/kg/h associated with increased mortality is incorporated into AKI diagnosis. We aimed to identify the urine-output threshold associated with increased AKI incidence and hypothesized that a higher urine output than a specified threshold, which differs from the predominantly used 0.5 mL/kg/h threshold, would be associated with an increased AKI incidence. This was a post-hoc analysis of a nationwide prospective observational study. This study included adult patients newly diagnosed with sepsis and requiring intensive care. Urine output on the day of sepsis diagnosis was categorized as low, moderate, or high (<0.5, 0.5-1.0, and >1.0 mL/kg/h, respectively), and we compared AKI incidence, renal replacement therapy (RRT) requirement, and 28-day survival by category. Estimated probabilities for these outcomes were also compared after adjusting for patient background and hourly fluid administration. Among 172 eligible patients, AKI occurred in 46.3%, 48.3%, and 53.1% of those with high, moderate, and low urine output, respectively. The probability of AKI was lower in patients with high urine output than in those with low output (43.6% vs 56.5%; P = .028), whereas RRT requirement was lower in patients with high and moderate urine output (11.7% and 12.8% vs 49.1%; P < .001). Patients with low urine output demonstrated significantly lower survival (87.7% vs 82.8% and 67.8%; P = .018). Cubic spline curves for AKI, RRT, and survival prediction indicated different urine-output thresholds, including <1.2 to 1.3 mL/kg/h for AKI and <0.6 to 0.8 mL/kg/h for RRT and mortality risk. Urine output >1.0 mL/kg/h on the day of sepsis diagnosis was associated with lower AKI incidence. The urine-output threshold was higher for developing AKI than for RRT requirement or mortality.

Performance of blood enterovirus and parechovirus polymerase chain reaction testing in young febrile infants: a prospective multicentre observational study

ObjectivesTo analyse the performance of blood enterovirus and parechovirus PCR testing (ev-PCR) for invasive bacterial infection (IBI) (isolation of a single bacterial pathogen in a blood or cerebrospinal fluid culture)...

Attainment of LDL-cholesterol target in high cardiovascular risk type 1 diabetic French people

As people with type 1 diabetes have increased risk of cardiovascular morbi-mortality, management of cardiovascular risk factors is of crucial importance. We assessed the prevalence and factors associated with LDL-cholesterol (LDL-c) target achievement in patients with type 1 diabetes at high and very-high cardiovascular risk. In this observational multicenter study, we included hospitalized patients with type 1 diabetes who had a fasting blood lipid analysis at admission. Cardiovascular risk level and LDL-c target values were defined according to ESC/EAS guidelines into force at admission: LDL-c target for very-high risk (VHR) and high risk (HR) patients was 1.4 and 1.8 mmol/l respectively for patients included from September 2019 (2019 guidelines) and 1.8 and 2.6 mmol/l respectively for patients included in 2016-2019 (2016 guidelines). LDL-c target attainment was assessed in HR and VHR patients, and factors associated with attainment were identified with multivariable analysis. We included 85 HR patients (median age 37y [interquartile range: 27;45], 64% females) and 356 VHR patients (49 [35;61] years, 42% females). In HR patients, 7% were treated with statins, and 35.3% achieved the LDL-c target. Increasing age (odds ratio 0.58 [95% confidence interval: 0.38;0.89]), body mass index (0.86 [0.75;0.98]), and HbA1c (0.69 [0.50;0.94]) were independently associated with lower odds of attaining LDL-c target. In VHR patients, 36% were treated with statins, and 17.4% achieved LDL-c target. Statin treatment (2.33 [1.22;4.43]), secondary prevention (2.33 [1.21;4.48]) and chronic renal failure (2.82 [1.42;5.61]) were associated with higher odds of attaining LDL-c target. Control of LDL-c is highly insufficient in both HR and VHR patients. Cardiovascular risk evaluation and better control of risk factors may help decrease cardiovascular morbi-mortality in patients with type 1 diabetes. NCT03449784.

Modifiable Factors Associated with Prolonged Dialysis Recovery Time and Fatigue in Hemodialysis Patients.

Dialysis recovery time (DRT) and fatigue are two important patient-reported outcomes that highly affect hemodialysis patients' well-being and survival. This study aimed to identify all modifiable dialysis-related factors, associated with DRT and fatigue, that could be addressed in future clinical trials. This multicenter observational study included adult patients, undergoing chronic hemodialysis for > 3 months during December 2023. Patients admitted to hospital, with cognitive problems, or active cancer were excluded. DRT was determined by asking over six sessions: "How long did it take you to recover from your last dialysis session?" Fatigue was assessed using the French-validated SONG-HD fatigue scale. Logistic regression analysis assessed the association between DRT>12 hours and fatigue score ≥4 with all dialysis-related factors. A sub-analysis of DRT-related factors was performed for very elderly ≥ 85 years. A total of 536 patients and 2967 sessions were analyzed. Mean age was 68.1 ±14.3 years, 60.9% were males, 33.2% had diabetes, 63.3% were on hemodiafiltration. Median dialysate sodium was 138 (136, 140). Median DRT was 140 (45, 440) minutes and 14.9% of patients had DRT >12 hours. Fatigue score was 3.1 ±2.3, 18% had no fatigue and 37.7% had a score ≥4. DRT and fatigue score were significantly associated. In multivariable regression analysis, intradialytic reduction in serum sodium and frequency of dialysis were significantly associated with DRT. Factors associated with fatigue included female sex and lower hemoglobin. In patients ≥85 years, hemodiafiltration was associated with prolonged DRT. Modifiable factors associated with prolonged DRT are not exactly similar to those associated with fatigue. Intradialytic reduction in serum sodium and low frequency of dialysis are two independent factors associated with longer DRT, with hemodiafiltration associated with longer recovery in very elderly patients. The hemoglobin level is the modifiable independent factor associated with fatigue. These modifiable factors can be addressed in future interventional trials in order to improve patients' outcomes.

Quadruple therapies show a higher eradication rate compared to standard triple therapy for Helicobacter pylori infection within the LEGACy consortium. A multicenter observational study in European and Latin American countries.

Gastric cancer (GC) is one of the most lethal malignancies worldwide. Helicobacter pylori is the primary cause of GC; therefore, its eradication reduces the risk of developing this neoplasia. There is extensive evidence regarding quadruple therapy with relevance to the European population. However, in Latin America, data are scarce. Furthermore, there is limited information about the eradication rates achieved by antibiotic schemes in European and Latin American populations. To compare the effectiveness of standard triple therapy (STT), quadruple concomitant therapy (QCT), and bismuth quadruple therapy (QBT) in six centers in Europe and Latin America. A retrospective study was carried out based on the LEGACy registry from 2017 to 2022. Data from adult patients recruited in Portugal, Spain, Chile, Mexico, and Paraguay with confirmed H. pylori infection who received eradication therapy and confirmatory tests at least 1month apart were included. Treatment success by each scheme was compared using a mixed multilevel Poisson regression, adjusting for patient sex and age, together with country-specific variables, including prevalence of H. pylori antibiotic resistance (clarithromycin, metronidazole, and amoxicillin), and CYP2C19 polymorphisms. 772 patients were incorporated (64.64% females; mean age of 52.93years). The total H. pylori eradication rates were 75.20% (255/339) with STT, 88.70% (159/178) with QCT, and 91.30% (191/209) with QBT. Both quadruple therapies (QCT-QBT) showed significantly higher eradication rates compared with STT, with an adjusted incidence risk ratio (IRR) of 1.25 (p: <0.05); and 1.24 (p: <0.05), respectively. The antibiotic-resistance prevalence by country, but not the prevalence of CYP2C19 polymorphism, showed a statistically significant impact on eradication success. Both QCT and QBT are superior to STT for H. pylori eradication when adjusted for country-specific antibiotic resistance and CYP2C19 polymorphism in a sample of individuals residing in five countries within two continents.

Incidence and Predictors of Cerebrovascular Accidents in Patients Undergoing Transcatheter Mitral Valve Repair with Mitraclip

Transcatheter mitral edge-to-edge repair (TEER) with transcatheter devices has become a mainstay in the minimally invasive treatment of patients with severe mitral regurgitation at increased surgical risk. Despite its apparently favorable risk profile, there is uncertainty on the risk and features of cerebrovascular accidents (CVA) early and long after TMVR. We aimed at appraising incidence and predictors of CVA in patients undergoing TEER. We explicitly queried the dataset of an ongoing multicenter prospective observational study dedicated to TEER with MitraClip (Abbott Vascular, Santa Clara, CA, USA). Incidence of CVA after TEER was formally appraised, and we explored also potential predictors of such event. Descriptive, bivariate and diagnostic accuracy analyses were performed. Out of 2238 patients undergoing TEER, CVA occurred in 33 (1.47% [95% confidence interval 1.02% to 2.06%]), including 6 (0.27% [0.10% to 0.58%]) inhospital strokes and 27 events after discharge (0.99% [0.66% to 1.44%]) over a median follow-up of of 14 months. Most CVA were major ischemic strokes, during the inhospital phase as well as subsequently. Overall, CVA were more common in patients with atrial fibrillation (p=0.018), renal dysfunction (p=0.032), higher EuroSCORE II (p=0.033), and, as expected, higher CHA2DS2-VASc score (p=0.033), despite the limited prognostic accuracy of such score. Notably, the occurrence of CVA did not confer a significantly increased risk of long-term death (p=0.136) or cardiac death (p=0.397). The incidence of CVA in patients undergoing TEER is low, with most events occurring after discharge, and being associated with pre-existing risk features. These findings, while reassuring on the safety of TEER, call for proactive antithrombotic therapy whenever CVA risk is increased before, as well as after such intervention.

A multicenter, prospective, non-interventional real-world study to assess the effectiveness of mecapegfilgrastim in preventing neutropenia in patients with gastrointestinal cancer.

Mecapegfilgrastim, a long-actinggranulocyte-colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S-1/capecitabine-based regimens or thefluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. Five hundred and sixty-one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S-1/capecitabine-based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S-1/capecitabine-based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. In a real-world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high-risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.

Long-term outcomes of the first prospective study of active surveillance for prostate cancer in Japan.

Active surveillance for prostate cancer was initiated in the early 2000s. We assessed the long-term outcomes of active surveillance in Japan. This multicenter prospective observational cohort study enrolled men aged 50-80years with stage cT1cN0M0 prostate cancer in 2002 and 2003. The eligibility criteria included serum prostate-specific antigen level ≤ 20ng/mL, ≤ 2 positive cores per 6-12 biopsy samples, Gleason score ≤ 6, and cancer involvement < 50% in the positive core. Patients were encouraged to undergo active surveillance. Prostate-specific antigen levels were measured bimonthly for 6months and every 3months thereafter. Triggers for recommending treatment were prostate-specific antigen doubling time of < 2years and pathological progression on repeat biopsy. Among 134 patients, 118 underwent active surveillance. The median age, prostate-specific antigen level at diagnosis, and maximum cancer occupancy were 70years, 6.5ng/mL, and 11.2%, respectively. Ninety-one patients had only one positive cancer core. The median observation period was 10.7years. At 1year, 65.7% underwent a repeat biopsy, and 37% of patients experienced pathological progression. The active surveillance continuation rates at 5, 10, and 15years were 28%, 9%, and 4%, respectively. One prostate cancer-related death occurred in a patient who refused treatment despite pathological progression at the one-year repeat biopsy. Active surveillance according to this study protocol was associated with conversion to the next treatment without delay, when indicated, despite the selection criteria and follow-up protocols being less rigorous than those recommended in current international guidelines.

Ceftolozane/Tazobactam for the Treatment of Adults With Cystic Fibrosis: Results From a French Prospective Cohort Study.

People with cystic fibrosis (pwCF) are particularly susceptible to respiratory infections, including those caused by multidrug-resistant (MDR) pathogens. Ceftolozane/tazobactam (C/T) is an antibacterial agent combination active against MDR gram-negative bacteria that has shown promising results in isolates from pwCF. This subanalysis is the first extensive observation of real-world C/T use in pwCF. The multicenter observational CONDUCT study included consecutive patients, some with cystic fibrosis, who received ≥1 dose of C/T at 28 centers throughout France. Patients were treated according to hospital standards and followed up until the end of C/T treatment (EOT). Among 260 patients who had received ≥1 dose of C/T, 63 were pwCF, including 12 with previous lung transplant. The median age was 34 years and 55.6% of patients were female. Pseudomonas aeruginosa was the most frequently isolated pathogen (n = 40/41 [97.6%]). Most tested P aeruginosa strains (n = 65/73 [91.5%]) and all other isolated strains (Escherichia coli, Citrobacter koseri, Proteus mirabilis, and Serratia marcescens) were susceptible to C/T. Most patients completed the treatment duration, including those with historical β-lactam hypersensitivity. Reasons for stopping treatment were planned EOT and improvement in condition; overall, 88.9% of patients (n = 56/63) experienced improvement in condition. No new safety signals were identified. Mean forced expiratory volume in 1 second improved from 1.33 L to 1.47 L before and after C/T treatment, respectively (n = 52; P = .057). C/T treatment was well tolerated and effective in pwCF, including those with previous β-lactam hypersensitivity.