International Multicenter Cohort Study Research Articles

#723 The impact of kidney function on arterial stiffness in COVID-19 survivors: an analysis from CARTESIAN Study

Abstract Background and Aims SARS-CoV-2 pandemic has been linked to an increased incidence of cardiovascular events, potentially due to accelerated vascular aging [1]. Conversely, impaired kidney function is known to contribute to the pathogenesis of heightened arterial stiffness, independent of traditional cardiovascular risk factors [2]. This study aimed to assess the impact of COVID-19 on arterial stiffness among a cohort of survivors of the first pandemic wave, with varying degrees of infection severity. The assessment was conducted at 6 ± 3 (T1) and 12 ± 3 months (T2) post-infection, with the population stratified based on kidney function. Method the CARTESIAN study, a large international multicenter cohort study, was designed to assess the long-term effects of COVID-19 on vascular aging. A total of 938 subjects were stratified into three groups based on their estimated glomerular filtration rate (eGFR) percentiles using the CKD-EPI_2021 equation: 1) >75th percentile, 2) 75th-25th percentile, and 3) <25th percentile, respectively. The same population was further categorized based on the severity of COVID-19 into three groups: 1) patients who were not hospitalized (No-Hosp), 2) subjects requiring hospitalization in a medical unit (Hosp), or 3) those in an intensive care unit (ICU). Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV). A hierarchical repeated measures mixed model analysis was conducted to compare cf-PWV across these groups (>75th, 75th-25th, and <25th groups, respectively). Results in the cross-section analysis (T1) <25th group exhibited higher age, increased cardiovascular risk factors, and higher prevalence of severe COVID-19 compared to the >75th group. Using hierarchical linear modeling, the <25th exhibited higher cf-PWV than the >75th group, even after adjusting for both all the random and fixed variables, included the three COVID-19 group (+0.51 m/s, p = 0.013). In longitudinal analysis, globally, no substantial changes were found in the cf-PWV between T1 and T2, remained significantly higher in the <25th group compared to the >75th group (p = 0.003), in a linear mixed model adjusted for all the random and fixed variables. Interestingly, a significant interaction between eGFR groups* COVID-19 groups was found in repeated measures analysis (p = 0.039). In particular, within ICU group, we found a significant increase of cf-PWV between 6- and 12-months in <25th group, from 8.64 [7.59-9.31] to 9.41 [8.89-10.41] m/s, p = 0.021) (Fig. 1). Conclusion the findings suggest that individuals with both lower eGFR and a history of severe COVID-19 may be at a heightened risk of accelerated arterial aging. Understanding these dynamics is crucial for targeted interventions to mitigate long-term cardiovascular consequences in COVID-19 survivors with kidney disease.

Defining Benchmarks for Pelvic Exenteration Surgery: A Multicentre Analysis of Patients with Locally Advanced and Recurrent Rectal Cancer.

To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement. This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres. 763 patients underwent PE, of which 464 patients (61%) had LARC and 299 (39%) had LRRC. 544 patients (71%) who met predefined lower risk criteria formed the benchmark cohort. For LARC patients, the calculated benchmark threshold for major complication rate was ≤44%; comprehensive complication index (CCI): ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For LRRC patients, the calculated benchmark threshold for major complication rate was ≤53%; CCI: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%. The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres.

Patterns of opioid use after surgical discharge: a multicentre, prospective cohort study in 25 countries.

Excessive opioid prescribing following surgery contributes to the growing opioid crisis. Prescribing practices are modifiable, yet data to guide appropriate prescription of opioids at surgical discharge remain sparse. This study aimed to evaluate factors associated with opioid consumption following discharge from surgery. An international prospective multicentre cohort study was performed recruiting adult patients undergoing common general, orthopaedic, gynaecological and urological surgery, with follow-up 7 days after discharge. The primary outcome measures were the quantities of prescribed and consumed opioids in oral morphine milligram equivalents. Descriptive and multivariable analyses were performed to investigate factors associated with the primary outcome measures. This analysis included 4273 patients from 144 hospitals in 25 countries. Overall, 1311 (30.7%) patients were prescribed opioids at discharge. For those patients prescribed opioids, mean (SD) 179 (240) oral morphine milligram equivalents were prescribed, yet only 81 (145) oral morphine milligram equivalents were consumed within the first 7 days after discharge. An increased dose of opioids prescribed at discharge was associated with an increased dose of opioids consumed during the follow-up period (β = 0.33 (95%CI 0.31-0.34), p < 0.001). The risk of prescribing more opioids than patients consumed increased as quantities of opioids prescribed at discharge exceeded 100 oral morphine milligram equivalents, independent of patient comorbidity, procedure and pain. Patients were prescribed more than twice the quantity of opioids they consumed in the first 7 days following discharge from surgery. Our data suggest that the current quantities of opioids provided at discharge exceed patient needs and may contribute to increasing community opioid use and circulation.

Abstract PO4-19-04: AXSANA – EUBREAST-3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy

Abstract Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy (SLNB) alone are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study was initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with axillary lymph node metastasis scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without confirmation using a minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ-BR 23, Lymph ICF and SOC-13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: 4336 patients from 284 study sites and 26 countries were enrolled in the study between June 2020 and June 2023. Among 3722 patients with a defined surgical concept 1631 women were scheduled for TAD, 1483 for ALND, 469 for SLNB, 25 for TLNB and 109 for other procedures. A target lymph node was marked in 2309 patients, most frequently using clips/coils (1850, 80.1%), followed by magnetic seeds (219, 9.5%), carbon ink (171, 7.4%), radar marker (80, 3.5%), radioactive seeds (4, 0.2%) and other techniques (24, 1.0%). Funding: AGO-B, GBG, Claudia-von Schilling Foundation, Ehmann Foundation, Eugen und Irmgard Hahn Foundation, AWOgyn, Merit Medical, Endomagnetics, Mammotome Contact information: Prof. Dr. Thorsten Kühn Department of Gynecology and Obstetrics University of Ulm, Germany Baumreute 37 D-73730 Esslingen Germany E-Mail: kuehn.thorsten@t-online.de Citation Format: Thorsten Kühn, Steffi Hartmann, Elmar Stickeler, Jana de Boniface, Oreste Davide Gentilini, Sarah Fröhlich, Franziska Ruf, Marc Thill, Michael Hauptmann, Guldeniz Karadeniz Cakmak, Isabel Rubio, Maria Luisa Gasparri, Michalis Kontos, Eduard-Alexandru Bonci, Laura Niinikoski, Bilge Aktas Sezen, Rosa Di Micco, Dawid Murawa, Geeta Kadayaprath, David Pinto, Florentia Peintinger, Matilda Appelgren, Janine M. Simons, Marjolein Smidt, Ellen Schlichting, Lukas Dostalek, Elisabeth Thiemann, Markus Hahn, Michael Schrauder, Semra Gunay, Gunay Gurleyik, Nina Helidon, Hagigat Valiyeva, Ashutosh Kothari, Marian Vanhoeij, Andraz Perhavec, Tsvetomir Ivanov, Dov Zippel, Lia Rebaza, Sarun Thongvitokomarn, Sibylle Loibl, Maggie Banys-Paluchowski. AXSANA – EUBREAST-3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-04.

Contemporary outcomes of left thoraco-abdominal esophagectomy due to cancer in the esophagus or gastroesophageal junction, a multicenter cohort study.

Surgery for cancer of the esophagus or gastro-esophageal junction can be performed with a variety of minimally invasive and open approaches. The left thoracoabdominal esophagectomy (LTE) is an open technique that gives an opportunity to operate in the chest and abdomen with excellent exposure of the gastro-esophageal junction through a single incision, and there is currently no equivalent minimally invasive technique available. The aim of this multi-institutional review was to study a large contemporary international study cohort of patients treated with LTE. An international multicenter cohort study was performed including all patients treated with LTE at six high-volume centers for gastro-esophageal cancer surgery between 2012 and 2022. Patient data were prospectively collected in each participating centers' institutional database. Information about patient, tumor, and treatment details were collected. The study cohort included a total of 793 patients treated with LTE during the study period. The most frequently observed complications were pneumonia in 185/727 (25.5%) patients and atrial fibrillation in 91/727 (12.5%). Anastomotic leak occurred in 35/727 (4.8%) patients; no patient suffered from conduit necrosis. Thirty-day mortality occurred in 15/785 (1.9%) patients and 90-day mortality in 39/785 (5.0%) patients. Factors with statistically significant association with survival were American Society for Anesthesiologists-score, tumor location, tumor stage, and tumor free resection margins. Neoadjuvant therapy was not associated with increased survival compared to surgery alone but neoadjuvant chemoradiotherapy compared to neoadjuvant chemotherapy showed statistically significant improved survival with hazard ratio 0.60 (95% confidence intervals:0.44-0.80, P = 0.001) in a multivariable adjusted model. This study demonstrates that LTE can be applied in selected patients with results that are comparable to other large studies of open and minimally invasive surgery for esophageal or gastro-esophageal cancer at high-volume centers.

Vena cava replacement and major hepatectomy for liver tumors: international multicenter retrospective cohort study.

Involvement of the inferior vena cava (IVC) and hepatic veins (HV) has been considered a relative contraindication to hepatic resection for primary and metastatic liver tumors. However, patients affected by tumors extending to the IVC have limited therapeutic options and suffer worsening of quality of life due to IVC compression. Cases of primary and metastatic liver tumors with vena cava infiltration from 10 international centers were collected (7 European, 1 US, 2 Brazilian, 1 Indian) were collected. Inclusion criteria for the study were major liver resection with concomitant vena cava replacement. Clinical data and short-term outcomes were analyzed. 36 cases were finally included in the study. Median tumor max size was 98mm (range: 25-250). A biliary reconstruction was necessary in 28% of cases, while a vascular reconstruction other than vena cava in 34% of cases. Median operative time was 462 min (range: 230-750), with 750 median ml of estimated blood loss and a median of one pRBC transfused intraoperatively (range: 0-27). Median ICU stay was 4 days (range: 1-30) with overall in-hospital stay of 15 days (range: 3-46), post-operative CCI score of 20.9 (range: 0-100), 12% incidence of PHLF grade B-C. Five patients died in a 90-days interval from surgery, 1 due to heart failure, 1 due to septic shock and 3 due to multiorgan failure. With a median follow-up of 17 months (interquartile range: 11-37), the estimated five-years overall survival was 48% (95% CI: 27%-66%), and five-year cumulative incidence of tumor recurrence was 55% (95% CI: 33%-73%). Major liver resections with vena cava replacement can be performed with satisfactory results in expert HPB centers. This surgical strategy represents a feasible alternative for otherwise unresectable lesions and is associated with favorable prognosis compared to non-operative management, especially in patients affected by intrahepatic cholangiocarcinoma.

An international multicenter cohort study on implantable cardioverter-defibrillators for the treatment of symptomatic children with catecholaminergic polymorphic ventricular tachycardia

BackgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT) may cause sudden cardiac death (SCD) despite medical therapy. Therefore, implantable cardioverter-defibrillators (ICDs) are commonly advised. However, there are limited data on the outcomes of ICD use in children. ObjectiveThe purpose of this study was to compare the risk of arrhythmic events in pediatric patients with CPVT with and without ICD. MethodsWe compared the risk of SCD in patients with RYR2 (ryanodine receptor 2) variants and phenotype-positive symptomatic patients with CPVT with and without ICD who were younger than 19 years and had no history of sudden cardiac arrest at phenotype diagnosis. The primary outcome was SCD; secondary outcomes were composite end points of SCD, sudden cardiac arrest, or appropriate ICD shocks with or without arrhythmic syncope. ResultsThe study included 235 patients, 73 with ICD (31.1%) and 162 without ICD (68.9%). Over a median follow-up of 8.0 years (interquartile range 4.3–13.4 years), SCD occurred in 7 patients (3.0%), of whom 4 (57.1%) were noncompliant with medications and none had an ICD. Patients with ICD had a higher risk of both secondary composite outcomes (without syncope: hazard ratio 5.85; 95% confidence interval 3.40–10.09; P < .0001; with syncope: hazard ratio 2.55; 95% confidence interval 1.50–4.34; P = .0005). Thirty-one patients with ICD (42.5%) experienced appropriate shocks, 18 (24.7%) inappropriate shocks, and 21 (28.8%) device-related complications. ConclusionSCD events occurred only in the no ICD group and in those not on optimal medical therapy. Patients with ICD had a high risk of appropriate and inappropriate shocks, which may be reduced with appropriate device programming. Severe ICD complications were common, and risks vs benefits of ICDs need to be considered.

Real-world effectiveness and safety of risankizumab in adult patients with plaque psoriasis: A 1-year international multicenter retrospective cohort study

Real-world effectiveness and safety of risankizumab in adult patients with plaque psoriasis: A 1-year international multicenter retrospective cohort study

Children’s orthopaedics

The April 2024 Children’s orthopaedics Roundup360 looks at: Ultrasonography or radiography for suspected paediatric distal forearm fractures?; Implant density in scoliosis: an important variable?; Gait after paediatric femoral shaft fracture treated with intramedullary nail fixation: a longitudinal prospective study; The opioid dilemma: navigating pain management for children’s bone fractures; 12- to 20-year follow-up of Dega acetabuloplasty in patients with developmental dysplasia of the hip; Physeal fractures of the distal ulna: incidence and risk factors for premature growth arrest; Analysis of growth after transphyseal anterior cruciate ligament reconstruction in children; Management of lateral condyle humeral fracture associated with elbow dislocation in children: a retrospective international multicentre cohort study.

O78: Risk of recurrence after surgical resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia (IPMN) with patterns of distribution and treatment

Abstract Introduction Recurrence patterns and treatment of recurrence post resection of invasive IPMN are poorly explored. This international multicentre cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for invasive IPMN. Method Patients undergoing pancreatic resection for invasive IPMN between January 2010 to December 2020 at 18 pancreatic centres were identified. Survival analysis was performed by the Kaplan Meier log rank test and multivariable logistic regression by Cox-Proportional Hazards modelling. Endpoints were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). Results Four hundred and fifty-nine patients were included (median, 70years; IQR, 64-76; male, 54 percent) with a median follow-up of 26.3 months (IQR, 13.0-48.1 months). Recurrence occurred in 209 patients (45.5 percent; median time to recurrence, 32.8 months, early recurrence [within 1year], 20.2 percent). Eighty-three (18.1 percent) patients experienced a local regional recurrence and 164 (35.7 percent) patients experienced distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (HR 1.09;p=0.669) One hundred and twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months (p&amp;lt;0.001), with no significant difference between treatment modalities. There was no significant difference in survival between location of recurrence (p=0.401). Conclusion Recurrence after pancreatic resection for invasive IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

Different Periampullary Types and Subtypes Leading to Different Perioperative Outcomes of Pancreatoduodenectomy: Reality and Not a Myth; An International Multicenter Cohort Study.

This international multicenter cohort study included 30 centers. Patients with duodenal adenocarcinoma (DAC), intestinal-type (AmpIT) and pancreatobiliary-type (AmpPB) ampullary adenocarcinoma, distal cholangiocarcinoma (dCCA), and pancreatic ductal adenocarcinoma (PDAC) were included. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were major morbidity (Clavien-Dindo 3b≥), clinically relevant post-operative pancreatic fistula (CR-POPF), and length of hospital stay (LOS). Results: Overall, 3622 patients were included in the study (370 DAC, 811 AmpIT, 895 AmpPB, 1083 dCCA, and 463 PDAC). Mortality rates were comparable between DAC, AmpIT, AmpPB, and dCCA (ranging from 3.7% to 5.9%), while lower for PDAC (1.5%, p = 0.013). Major morbidity rate was the lowest in PDAC (4.4%) and the highest for DAC (19.9%, p < 0.001). The highest rates of CR-POPF were observed in DAC (27.3%), AmpIT (25.5%), and dCCA (27.6%), which were significantly higher compared to AmpPB (18.5%, p = 0.001) and PDAC (8.3%, p < 0.001). The shortest LOS was found in PDAC (11 d vs. 14-15 d, p < 0.001). Discussion: In conclusion, this study shows significant variations in perioperative mortality, post-operative complications, and hospital stay among different periampullary cancers, and between the ampullary subtypes. Further research should assess the biological characteristics and tissue reactions associated with each type of periampullary cancer, including subtypes, in order to improve patient management and personalized treatment.

Comparison of Angiographic Outcomes of Woven EndoBridge and Balloon‐Assisted Coiling for the Treatment of Ruptured Wide‐Necked Aneurysms: A Multicentric Study

Background The optimal endovascular approach for acutely ruptured wide‐neck intracranial aneurysms remains uncertain, and the use of stent‐assisted coiling or flow diversion is controversial due to antiplatelet therapy requirements and potential risks. Various techniques have been developed to address these challenges, including balloon‐assisted coiling (BAC) and intrasaccular flow‐disruption. The Woven EndoBridge (WEB) is an intrasaccular device that has shown a favorable efficacy and safety profile for ruptured aneurysms with minimal rebleeding rates. We aimed to compare the clinical and radiological outcomes between WEB and BAC in a cohort of patients with ruptured wide‐necked intracranial aneurysms. Methods In this international multicenter cohort study, we included consecutive patients treated for ruptured wide‐neck intracranial aneurysms with either WEB or BAC at 4 neurovascular centers. The primary effectiveness outcome was complete aneurysm occlusion at the final imaging follow‐up using the Raymond–Roy scale. Secondary outcomes included a composite of periprocedural hemorrhagic/ischemia‐related complications and favorable functional outcome. Results The study included 104 patients treated with WEB and 107 patients treated with BAC. Of the patients, 60.5% in the WEB group and 53% in the BAC group achieved complete occlusion, with no significant difference between the 2 groups after adjusting for covariates (adjusted odds ratio [OR] = 1.02; 95% CI 0.46–2.25; P = 0.964). The odds of favorable functional outcome did not significantly differ between the WEB (74.8%) and BAC groups (77.4%, adjusted OR = 1.45; 95% CI 0.65–3.24; P = 0.368). Procedure‐related complications were similar in both groups (WEB: 9.6%, BAC: 10.3%, P = 0.872), with no significant difference observed in the rates of ischemic events (WEB: 6.7% versus BAC: 2.8%; P = 0.180) and hemorrhagic events (WEB: 3.8% versus BAC: 7.5%; P = 0.255) between the 2 groups. Conclusion In conclusion, both WEB and BAC techniques showed similar effectiveness and safety outcomes in treating ruptured wide‐neck intracranial aneurysms. Further prospective comparative studies are needed to better guide treatment decisions for this patient population.

Let's Agree to Disagree on Operative Versus Nonoperative Treatment for Distal Radius Fractures in Older People: Protocol for a Prospective International Multicenter Cohort Study.

Distal radius fractures are the most frequently encountered fractures in Western societies, typically affecting patients aged 50 years and older. Although this is a common injury, the best treatment for these fractures in older patients is still under debate. This prospective study aims to compare the outcome of operatively and nonoperatively treated distal radius fractures in the older population. Only patients with distal radius fractures for which equipoise regarding the optimal treatment exists will be included. This prospective international multicenter observational cohort study will be designed as a natural experiment. Natural experiments are observational studies in which treatment allocation is determined by factors outside the control of the investigators but also (largely) independent of patient characteristics. Patients aged 65 years and older with an acute distal radius fracture will be considered for inclusion. Treatment allocation (operative vs nonoperative) will be based on the local preferences of the treating hospital either in Switzerland or the Netherlands. Hence, the process governing treatment allocation resembles that of randomization. Patients will be identified after treatment has been initiated. Based on the radiographs and baseline information of the patient, an expert panel of 6 certified trauma surgeons from 2 regions will provide their treatment recommendation. Only patients for whom the experts disagree on treatment recommendations will ultimately be included in the study (ie, for whom there is a clinical equipoise). For these patients, both operative and nonoperative treatment of distal radius fractures are viable, and treatment choice is predominantly determined by personal or local preference. The primary outcome will be the Patient-Rated Wrist Evaluation score at 12 weeks. Secondary outcomes will include the Physical Activity Score for the Elderly, the EQ questionnaire, pain, the living situation, range of motion, complications, and radiological outcomes. By including outcomes such as living situation and the Physical Activity Score for the Elderly, which are not relevant for younger cohorts, valuable information to tailor treatment to the needs of the older population can be gained. According to the sample size collection, which was based on the minimal important clinical difference of the Patient-Rated Wrist Evaluation, 92 patients will have to be included, with at least 46 patients in each treatment group. Enrollment began in July 2023 and is expected to continue until summer 2024. The final follow-up will be 2 years after the last patient is included. Although many trials on this topic have previously been published, there remains an ongoing debate regarding the optimal treatment for distal radius fractures in older patients. This observational study, which will use a fairly new methodological study design, will provide further information on treatment outcomes for older patients with distal radius fractures for which to date equipoise exists regarding the optimal treatment. DERR1-10.2196/52917.

Sex differences in post-acute neurological sequelae of SARS-CoV-2 and symptom resolution in adults after coronavirus disease 2019 hospitalization: an international multi-centre prospective observational study.

Although it is known that coronavirus disease 2019 can present with a range of neurological manifestations and in-hospital complications, sparse data exist on whether these initial neurological symptoms of coronavirus disease 2019 are closely associated with post-acute neurological sequelae of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2; PANSC) and whether female versus male sex impacts symptom resolution. In this international, multi-centre, prospective, observational study across 407 sites from 15 countries (30 January 2020 to 30 April 2022), we report the prevalence and risk factors of PANSC among hospitalized adults and investigate the differences between males and females on neurological symptom resolution over time. PANSC symptoms included altered consciousness/confusion, fatigue/malaise, anosmia, dysgeusia and muscle ache/joint pain, on which information was collected at index hospitalization and during follow-up assessments. The analysis considered a time to the resolution of individual and all neurological symptoms. The resulting times were modelled by Weibull regression, assuming mixed-case interval censoring, with sex and age included as covariates. The model results were summarized as cumulative probability functions and age-adjusted and sex-adjusted median times to resolution. We included 6862 hospitalized adults with coronavirus disease 2019, who had follow-up assessments. The median age of the participants was 57 years (39.2% females). Males and females had similar baseline characteristics, except that more males (versus females) were admitted to the intensive care unit (30.5 versus 20.3%) and received mechanical ventilation (17.2 versus 11.8%). Approximately 70% of patients had multiple neurological symptoms at the first follow-up (median = 102 days). Fatigue (49.9%) and myalgia/arthralgia (45.2%) were the most prevalent symptoms of PANSC at the initial follow-up. The reported prevalence in females was generally higher (versus males) for all symptoms. At 12 months, anosmia and dysgeusia were resolved in most patients, although fatigue, altered consciousness and myalgia remained unresolved in >10% of the cohort. Females had a longer time to the resolution (5.2 versus 3.4 months) of neurological symptoms at follow-up for those with more than one neurological symptom. In the multivariable analysis, males were associated with a shorter time to the resolution of symptoms (hazard ratio = 1.53; 95% confidence interval = 1.39-1.69). Intensive care unit admission was associated with a longer time to the resolution of symptoms (hazard ratio = 0.68; 95% confidence interval = 0.60-0.77). Post-discharge stroke was uncommon (0.3% in females and 0.5% in males). Despite the methodological challenges involved in the collection of survey data, this international multi-centre prospective cohort study demonstrated that PANSC following index hospitalization was high. Symptom prevalence was higher and took longer to resolve in females than in males. This supported the fact that while males were sicker during acute illness, females were disproportionately affected by PANSC.

Benefit, recurrence pattern, and toxicity to adjuvant anti-PD-1 monotherapy varies by ethnicity and melanoma subtype: An international multicenter cohort study

Anti-Program-Death-1 (PD-1) is a standard adjuvant therapy for patients with resected melanoma. We hypothesized that there are discrepancies in survival, recurrence pattern and toxicity to adjuvant PD-1 between different ethnicities and melanoma subtypes. We performed a multicenter cohort study incorporating 6 independent institutions in Australia, China, Japan, and the United States. The primary outcomes were recurrence free survival (RFS) and overall survival (OS). Secondary outcomes were disease recurrence patterns and toxicities. In total 534 patients were included. East-Asian/Hispanic/African reported significantly poorer RFS/OS. Nonacral cutaneous or melanoma of unknown primary reported the best RFS/OS, followed by acral, and mucosal was the poorest. Within the nonacral cutaneous or melanoma of unknown primary subtypes, East-Asian/Hispanic/African reported significantly poorer RFS/OS than Caucasian. In the multivariate analysis incorporating ethnicity/melanoma-subtype/age/sex/stage/lactate dehydrogenase/BRAF (v-Raf murine sarcoma viral oncogene homolog B)-mutation/adjuvant radiotherapy, East-Asian/Hispanic/African had independently significantly poorer outcomes (RFS: HR, 1.71; 95% CI, 1.19-2.44 and OS: HR, 2.34; 95% CI, 1.39-3.95), as was mucosal subtype (RFS: HR, 3.25; 95% CI, 2.04-5.17 and OS: HR, 3.20; 95% CI, 1.68-6.08). Mucosal melanoma was an independent risk factor for distant metastasis, especially liver metastasis. East-Asian/Hispanic/African had significantly lower incidence of gastrointestinal/musculoskeletal/respiratory/other-rare-type-toxicities; but higher incidences of liver toxicities. A retrospective study. Ethnicity and melanoma subtype are associated with survival and recurrence pattern in melanoma patients treated with adjuvant anti-PD-1. Toxicity profile differs by ethnicity and may require a precision toxicity surveillance strategy.

As simple as it sounds? The treatment of simple bone cysts in the proximal femur in children and adolescents: Retrospective multicenter EPOS study of 74 patients.

Simple bone cysts are among the most prevalent benign cystic tumor-like lesions in children. Proximal femoral simple bone cysts may require specific treatment because of increased fracture risk. With limited literature available on this specific localization, consensus regarding optimal treatment is lacking. We present a large international multicenter retrospective cohort study on proximal femoral simple bone cysts. All consecutive pediatric patients with proximal femoral simple bone cyst from 10 tertiary referral centers for musculoskeletal oncology were included (2000-2021). Demographics, primary treatment, complications, and re-operations were evaluated. Primary outcomes were time until full weight-bearing and failure-free survival. Overall, 74 simple bone cyst patients were included (median age 9 years (range = 2-16), 56 (76%) male). Median follow-up was 2.9 years (range = 0.5-21). Index procedure was watchful waiting (n = 6), percutaneous procedure (n = 12), open procedure (n = 50), or osteosynthesis alone (n = 6). Median time until full weight-bearing was 8 weeks (95% confidence interval = 0.1-15.9) for watchful waiting, 9.5 (95% confidence interval = 3.7-15.3) for percutaneous procedure, 11 (95% confidence interval = -0.7 to 13.7) for open procedure, and 6.5 (95% confidence interval = 5.9-16.1) for osteosynthesis alone (p = 0.58). Failure rates were 33%, 58%, 29%, and 0%, respectively (p = 0.069). Overall failure-free survival at 1, 2, and 5 years was 77.8% (95% confidence interval = 68.2-87.4), 69.5% (95% confidence interval = 58.5-80.5), and 62.0% (95% confidence interval = 47.9-76.1), respectively. A preferred treatment for proximal femoral simple bone cysts remains unclear, with comparable failure rates and times until full weight-bearing. Watchful waiting may be successful in certain cases. If not feasible, osteosynthesis alone can be considered. Treatment goals should be cyst control, minimizing complications and swift return to normal activities. Therefore, an individualized balance should be made between undertreatment, with potentially higher complication risks versus overtreatment, resulting in possible larger interventions and accompanying complications. Level IV, retrospective multicentre study.

The five periampullary cancers, not just different siblings but different families: an international multicentre cohort study

The five periampullary cancers, not just different siblings but different families: an international multicentre cohort study

Opioid analgesia and severity of acute pancreatitis: An international multicentre cohort study on pain management in acute pancreatitis

Opioid analgesia and severity of acute pancreatitis: An international multicentre cohort study on pain management in acute pancreatitis

The differences in lymph node metastases patterns among non-pancreatic periampullary cancers and histological subtypes: an international multicenter retrospective cohort study and systematic review

The differences in lymph node metastases patterns among non-pancreatic periampullary cancers and histological subtypes: an international multicenter retrospective cohort study and systematic review

How different are accuracies of clinicians' prediction of survival by assessment methods?

No standardized method has been established for evaluating the accuracy of a clinicians' prediction of survival (CPS). Till now, no study has compared the accuracy of CPS according to the evaluation methods using the same dataset. We aimed to examine the accuracy of CPS by different statistical approaches in patients with far-advanced cancer. The current study was a secondary analysis of an international multicenter prospective cohort study. Newly admitted patients with advanced cancer were enrolled in palliative care units (PCUs) in Japan, Korea, and Taiwan. We obtained the temporal CPS at enrollment. The patients were classified into groups of days (≤7 days) and weeks (≤30 days) based on CPS and actual survival (AS). We evaluated the accuracy of CPS by the distribution, area under the receiver operating characteristics curve (AUROCs), and an estimate ±33% of AS. A total of 2,571 patients were assessed and admitted in 37 PCUs between January 2017 and September 2018. As for the "days" category, the distribution of AS is larger than that of CPS, however, the results are reversed in the "weeks" category. The AUROCs showed over 80% discrimination for both the "days" and "weeks" categories. Accurate CPS within ±33% of AS was approximately 30% in both "days" and "weeks" categories. We showed a discrepancy of approximately 30-80% in the accuracy of CPS among three different analysis methods: distribution, AUROC, and AS comparison. Considering the low accuracy of AS comparisons, clinicians should provide a wide range of survival time. CPS was able to effectively discriminate and may be useful for risk stratification.