Multicenter Prospective Observational Cohort Research Articles

Bone morphogenetic protein 10 as predictor for adverse outcomes in patients with atrial fibrillation

Abstract Background Patients with atrial fibrillation (AF) face an increased risk of death and major adverse cardiovascular events (MACE). Bone morphogenetic protein 10 (BMP10) is a novel atrial-specific biomarker, but data about its prognostic value in AF patients are lacking. Purpose We aimed to assess the predictive value of BMP10 for death and MACE in AF patients in comparison to N-terminal prohormone of B-type natriuretic peptide (NT-proBNP). Methods Baseline concentrations of BMP10 and NT-proBNP were measured in stable patients with AF enrolled in Swiss-AF, a prospective multicenter observational cohort study. Primary outcomes were all-cause death and MACE (composite of heart failure hospitalization, cardiovascular death, stroke, systemic embolism, myocardial infarction). Measures of discriminative power were used to compare multivariable Cox proportional hazard models using the different biomarkers. Results A total of 2219 AF patients were included with a median follow-up of 4.3 years (IQR 3.9, 5.1). Mean age was 73±9 years and 27% were women. Incidence rate per 100 patient-years of all-cause death and MACE increased across BMP10 quartiles (Figure 1). In the multivariable adjusted Cox proportional hazard model, the hazard ratio (HR) and 95% confidence interval (CI) of BMP10 was 1.60 (1.37; 1.87) to predict all-cause death, and 1.54 (1.35; 1.76) to predict MACE. For all-cause death, the C-index (95% CI) was 0.783 (0.763; 0.809) for BMP10, 0.784 (0.765; 0.810) for NT-proBNP, and 0.789 (0.771; 0.815) for both biomarkers combined. For MACE, the C-index (95% CI) was 0.732 (0.715; 0.754) for BMP10, 0.747 (0.731; 0.768) for NT-proBNP, and 0.750 (0.734; 0.771) for both biomarkers combined. When grouping patients according to clinical used NT-proBNP categories (<300, 300–900, >900 ng/l), higher incidence rates and adjusted HRs were observed for the primary outcomes in patients with high BMP10 in the categories of low NT-proBNP (all-cause death aHR 2.28 [1.15; 4.52], MACE aHR 1.88 [1.07; 3.28]) and high NT-proBNP (all-cause death aHR 1.61 [1.14; 2.26], MACE aHR 1.38 [1.07; 1.80]) (Figure 2). Conclusion The novel atrial-specific biomarker BMP10 strongly predicts all-cause death and MACE in patients with AF. BMP10 provides additional prognostic information in low- and high-risk patients according to NT-proBNP stratification. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swiss National Science Foundation, Swiss Heart Foundation

Healing of ExcisionAl wounds on Lower legs by Secondary intention (HEALS) cohort study. Part 2: feasibility data from a multicentre prospective observational cohort study to inform a future randomized controlled trial.

Compression therapy is considered beneficial for postsurgical lower leg wound healing by secondary intention; however, there is a lack of supportive evidence. To plan a randomized controlled trial (RCT), suitable data are needed. To determine the feasibility of recruitment and estimate recruitment rate; to understand the standard postoperative wound management pathway; to determine uptake of optional additional clinic visits for healing confirmation; and to explore patient acceptability of compression bandaging and plan a future RCT. Participant recruitment was performed from secondary care dermatology clinics, during a period of 22 months. Inclusion criteria were age ≥ 18 years, planned excision of keratinocyte cancer on the lower leg with healing by secondary intention and an ankle-brachial pressure index of ≥ 0.8. Exclusion criteria were planned primary closure/graft or flap; inability to receive, comply with or tolerate high compression; planned compression; or suspected melanoma. Patients were followed up weekly (maximum 6 months) in secondary care clinics and/or by telephone. Information was collected on healthcare resource use, unplanned compression, wound healing and an optional clinic visit to confirm healing. This study recruited 58 patients from 9 secondary care dermatology clinics over 22 months. Mean recruitment/centre/month was 0.8 (range 0.1-2.3). Four centres had dedicated Research Nurse support. The analysis population (n = 53) had weekly follow-up assessments. Standard care clinical contacts were: general practitioner (7 visits; 1.2%), community nurse (169; 28.5%), practice nurse visits (189; 31.8%) and dermatology clinic visits (138; 23.2%). Participants whose wounds healed (34 of 45; 75.6%) attended an optional clinic visit. Data were obtained to inform a future RCT. Recruitment rates were found to be higher in centres with dedicated research support. People would be willing to take part in a trial and attend a confirmation of healing visit.

Healing of ExcisionAl wounds on Lower legs by Secondary intention (HEALS) cohort study. Part 1: a multicentre prospective observational cohort study in patients without planned compression.

There is no agreed treatment pathway following excision of keratinocyte cancer (KC). Compression therapy is considered beneficial for secondary intention healing on the lower leg; however, there is a lack of supportive evidence. To plan a randomized controlled trial (RCT), suitable data are needed. We report a multicentre prospective observational cohort study in this patient population with the intention of informing a future trial design. To estimate the time to healing in wounds healing by secondary intention without planned postoperative compression, following excision of KC on the lower leg; to characterize the patient population, including factors affecting healing; and to assess the incidence of complications. This was a multicentre prospective observational cohort study. Inclusion criteria were age ≥ 18 years with planned excision of KC on the lower leg and healing by secondary intention, an ankle-brachial pressure index (ABPI) of ≥ 0.8; and written informed consent. Exclusion criteria included planned excision with primary closure, skin graft or flap; compression therapy for another indication; planned compression; inability of patient to receive, comply with or tolerate high compression; or a suspected diagnosis other than KC. This study recruited 58 patients from 9 secondary care dermatology clinics. In the analysis population (n = 53), mean age was 81 years (range 25-97 years), median time to healing was 81 days (95% CI 73-92) and 45 patients (84.9%) had healing of the wound at the 6-month follow-up. The healing prognostic factors were wound parameters and ABPI. Wound infections occurred in 16 participants (30.2%). Four patients (7.5%) were admitted to hospital; three because of an infection and one because of a fall. The collected data have informed the RCT preparation. A relatively high proportion (7.5-15%) of unhealed wounds, infection and hospital admissions demonstrate the need for clearly establishing potentially effective treatments to improve outcomes for this population.

I-CARE, a European Prospective Cohort Study Assessing Safety and Effectiveness of Biologics in Inflammatory Bowel Disease

There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators. I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment. A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia. I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).

Functional status in older patients with cancer and a frailty risk profile: A multicenter observational study

IntroductionFunctional status (FS) and frailty are significant concerns for older adults, especially those with cancer. Data on FS (Activities of Daily Living [ADL]; Instrumental Activities of Daily Living [IADL]) and its evolution during cancer treatment in older patients and a frailty risk profile are scarce. Therefore, this study examines FS and its evolution in older patients with cancer and a frailty risk profile and investigates characteristics associated with functional decline. Material and MethodsThis secondary data-analysis, focusing on FS, uses data from a large prospective multicenter observational cohort study. Patients ≥70 years with a solid tumor and a frailty risk profile based on the G8 screening tool (score ≤ 14) were included. A geriatric assessment was performed including evaluation of FS based on ADL and IADL. At approximately three months of follow-up, FS was reassessed. Univariable and multivariable logistic regression analyses were used to identify predictive factors for functional decline in ADL and IADL. ResultsData on ADL and IADL were available at baseline and follow-up in 3388 patients. At baseline 1886 (55.7%) patients were dependent for ADL, whereas 2085 (61.5%) patients were dependent at follow-up. Functional decline was observed in 23.6% of patients. For IADL 2218 (65.5%) patients were dependent for IADL, whereas 2591 (76.5%) patients were dependent at follow-up. Functional decline in IADL was observed in 41.0% of patients. In multivariable analysis, disease stage III or IV, comorbidities, falls history in the past twelve months, and FS measured by IADL were predictive factors for functional decline in both ADL and IADL. Other predictive factors for functional decline in ADL were polypharmacy, Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) score 2–4, and cognitive impairment, and for functional decline in IADL were female sex, fatigue, and risk for depression. DiscussionFunctional impairments are frequent in older persons with cancer and a frailty risk profile, and several characteristics are identified that are significantly associated with functional decline. Therefore, FS is an essential part of the geriatric assessment which should be standard of care for this patient population. Next step is to proceed with directed interventions with the aim to limit the risk of functional decline as much as possible.

OS07.2.A Evaluation of Intraoperative Surgical Adjuncts and Resection of Glioblastoma (ELISAR GB): A UK and Ireland multicentre, prospective observational cohort study

Abstract Background Despite operative and adjuvant therapies, glioblastoma remains incurable, with the extent of resection being one of few treatments that can improve survival. To improve resection, operative adjuncts are used, with neuronavigation and 5-aminolevulinic acid (5-ALA) recommended as a standard of care in those aimed for maximal safe resection. Despite the standards, meta-analysis concluded that the impact of 5-ALA on the extent of surgical resection is of low quality due to bias in reporting tumour location and additional image guidance used, factors impacting on extent of resection as well as short-term neurological outcomes being uncertain. Therefore we aimed to evaluate the availability and use of 5-ALA and other adjuncts and compare surgical outcomes of 5-ALA-guided versus non-5-ALA-guided resections. Material and Methods A multicenter prospective observational cohort study was conducted across 27 out of 31 available centres in the UK and Ireland from 6 January until 19 March 2020. Inclusion criteria included adults with first diagnosis, supratentorial glioblastoma undergoing resection. Primary outcomes included: i) the availability and use of surgical adjuncts and ii) complete resection of enhancing tissue (CRET). Secondary outcomes included adverse events, new onset of postoperative neurological deficit and post-operative neurological function. Descriptive and inferential statistics were used for analysis with a p-value <0.05 deemed significant. Results 232 consecutive cases were identified. 142/232 cases were aimed for maximal safe resection subsequently divided into 5-ALA-guided (n=92) versus non-5-ALA-guided (n=50) resections. 5-ALA and neuronavigation were available across all centres. Neuronavigation and 5-ALA were used in 91% (n=129/142) and 65% (n=92/142) of cases aimed for maximal safe resection whereas 83% (n=75/90) and 49% (n=44/90) for debulk surgery. 35 unique combinations of surgical adjuncts were used in 232 operations. 5-ALA-guided resection yielded a higher percentage of CRET than without (55% versus 28%, p < 0.01). The two groups showed no difference in adverse events (p=0.98), new onset of neurological deficit (p=0.88) nor neurological function (p=0.7). A logistic regression analysis showed that 5-ALA was an important predictor of CRET regardless of additional adjuncts used (OR 2.4, CI 0.96-5.97, P = 0.05), tumour location and molecular characterisation (OR 3.48, CI 1.61-7.51, P <0.01). Conclusion Firstly, we showed that 5-ALA is not always used for glioblastoma aimed for CRET. Secondly, we report a great heterogeneity of adjuncts used for resection, possibly explained by a lack of high-quality evidence and surgeon training. Thirdly we demonstrate that 5-ALA-guided resection leads to higher percentage of CRET regardless of other adjuncts used, tumour location and molecular characterisation.

Improving prediction of response to neoadjuvant treatment in patients with breast cancer by combining liquid biopsies with multiparametric MRI: protocol of the LIMA study – a multicentre prospective observational cohort study

IntroductionThe response to neoadjuvant chemotherapy (NAC) in breast cancer has important prognostic implications. Dynamic prediction of tumour regression by NAC may allow for adaption of the treatment plan before completion,...

Adherence to antidepressant therapy: clinical experience on the example of agomelatine

The review article provides data on the prevalence and treatment problems of depression, highlights the issues of adherence to antidepressant therapy, investigation of the safety and efficacy of agomelatine in real clinical settings. The results of a prospective observational multicenter cohort study of agomelatine in clinical practice are analyzed in detail, taking into account the effect of treatment on the social functioning of patients. The results obtained in a sample representative for depression, including patients with comorbidities, confirm the long-term efficacy and good tolerability of agomelatine in daily practice, which is the basis for adherence to therapy and achievement of the goal of depression treatment

Prospective Cohort Study of Depression During Pregnancy and the Postpartum Period in Women With Epilepsy vs Control Groups.

Assess the incidence and factors associated with major depressive episodes (MDEs) and symptoms of depression and anxiety during pregnancy and postpartum periods in pregnant women with epilepsy (PWWE) compared with healthy pregnant women (HPW) and nonpregnant women with epilepsy (NPWWE) in comparable timeframes. Previous studies have reported higher rates of postpartum depression in women with epilepsy compared with women without epilepsy. However, the incidence of MDE using a structured interview during pregnancy and postpartum has not been directly compared with control groups, and the comparison of depression and anxiety symptoms and the role of associated factors remain ambiguous. The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study is a multicenter NIH-funded prospective observational parallel group cohort study of PWWE and their children. This report examines mood disorders. Unlike previous epilepsy pregnancy studies, the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-IV (SCID) provided lifetime diagnoses, and repeated SCID mood modules assessed for MDE, the a priori primary outcome. Symptoms of depression (Beck Depression Inventory [BDI] and Edinburg Postnatal Depression Scale [EPDS]) and anxiety (Beck Anxiety Inventory [BAI]) were also assessed along with multiple clinical factors. This study included PWWE (n = 331) and HPW (n = 102) during pregnancy and postpartum and NPWWE (n = 102) at comparable times. No difference in SCID-diagnosed MDE incidence was found across groups, but BDI depressive symptoms were worse during pregnancy in PWWE vs NPWWE and during postpartum vs HPW and NPWWE. BAI anxiety symptoms were worse during pregnancy in PWWE vs HPW and NPWWE and during postpartum vs HPW. Factors associated with MDE during pregnancy/postpartum for PWWE included >1 seizure/90 days, anticonvulsant polytherapy, unplanned pregnancy, and lifetime history of mood disorder. Suicidal ideation from BDI or EPDS was related to BAI anxiety symptoms. Although SCID-based MDE did not differ across groups, this prospective study confirms higher rates of psychiatric symptoms in patients with epilepsy during pregnancy and postpartum, provides new data on associated factors, and underscores the importance of anxiety in risk for depression and thoughts of death/dying or suicide. Given the risks, PWWE should be routinely assessed and symptomatic patients should be offered treatment. This study is registered at ClinicalTrials.gov as NCT01730170.

A Pragmatic Study on Nurse-Led Home Phototherapy

BACKGROUND Narrowband ultraviolet phototherapy is a safe and effective treatment option for chronic skin conditions. The requirements of clinic-based phototherapy can be burdensome, with home-based phototherapy as a reasonable alternative. OBJECTIVE This study aimed to analyze the effects of a nurse-led home phototherapy program and describe the clinical resources required. METHODS A pragmatic multicenter prospective observational cohort study was conducted from 2019 to 2021. Eighteen participants were enrolled in the program and followed for 9 months. Outcome measures included clearance rates, erythema incidence, Dermatology Life Quality Index, the burden of treatment scores, dermatologic medication usage, and clinic contacts. RESULTS Fourteen of the 18 patients (77.8%) reported high skin clearance. Mild erythema was common, moderate erythema was rare, and two episodes of severe erythema were recorded overall. Dermatology Life Quality Index and burden of treatment impact were minimal. Adjunct topical medications decreased by half. Nurses successfully reached participants up to the 3-month time point, with completed contacts decreasing over time. Unplanned contacts included phone calls and emails. CONCLUSION Dermatology nurses possess the skills needed to lead safe and effective home phototherapy programs. Although this pragmatic study was small, results are optimistic for the future of nurse-led home phototherapy.

Prospective multicentre observational cohort to assess quality of life, functional outcomes and cost-effectiveness following minimally invasive surgical techniques for rectal cancer in ‘dedicated centres’ in the Netherlands (VANTAGE trial): a protocol

IntroductionTotal mesorectal excision is the standard of care for rectal cancer, which can be performed using open, laparoscopic, robot-assisted and transanal technique. Large prospective (randomised controlled) trials comparing these techniques...

Cerebral small vessel disease and perihematomal edema formation in spontaneous intracerebral hemorrhage

ObjectiveBlood-brain barrier (BBB) dysfunction is implicated in the pathophysiology of cerebral small vessel disease (cSVD)-related intracerebral hemorrhage (ICH). The formation of perihematomal edema (PHE) is presumed to reflect acute BBB permeability following ICH. We aimed to assess the association between cSVD burden and PHE formation in patients with spontaneous ICH.MethodsWe selected patients with spontaneous ICH who underwent 3T MRI imaging within 21 days after symptom onset from a prospective observational multicenter cohort study. We rated markers of cSVD (white matter hyperintensities, enlarged perivascular spaces, lacunes and cerebral microbleeds) and calculated the composite score as a measure of the total cSVD burden. Perihematomal edema formation was measured using the edema extension distance (EED). We assessed the association between the cSVD burden and the EED using a multivariable linear regression model adjusting for age, (log-transformed) ICH volume, ICH location (lobar vs. non-lobar), and interval between symptom onset and MRI.ResultsWe included 85 patients (mean age 63.5 years, 75.3% male). Median interval between symptom onset and MRI imaging was 6 days (IQR 1–19). Median ICH volume was 17.0 mL (IQR 1.4–88.6), and mean EED was 0.54 cm (SD 0.17). We found no association between the total cSVD burden and EED (B = −0.003, 95% CI −0.003–0.03, p = 0.83), nor for any of the individual radiological cSVD markers.ConclusionWe found no association between the cSVD burden and PHE formation. This implies that mechanisms other than BBB dysfunction are involved in the pathophysiology of PHE.

Association of Nasopharyngeal and Serum Glutathione Metabolism with Bronchiolitis Severity and Asthma Risk: A Prospective Multicenter Cohort Study.

Infants hospitalized for bronchiolitis are at high risk for asthma. Glutathione-related metabolites may antagonize oxidative stress, which induces airway injuries in respiratory infection and subsequent airway remodeling. However, little is known about the relationship of glutathione-related metabolites with bronchiolitis severity and the risk of asthma. In a multicenter prospective observational cohort study of infants hospitalized for bronchiolitis, we measured nasopharyngeal and serum glutathione-related metabolites by using liquid chromatography–tandem mass spectrometry. We then examined their association with bronchiolitis severity (defined by positive pressure ventilation (PPV) use). We also identified severity-related glutathione-related metabolite signatures and examined their association with asthma at age 6 years. In 1013 infants, we identified 12 nasopharyngeal and 10 serum glutathione-related metabolites. In the multivariable models, lower relative abundances of seven metabolites, e.g., substrates of glutathione, including cysteine (adjOR 0.21, 95%CI 0.06–0.76), glycine (adjOR 0.25, 95%CI 0.07–0.85), and glutamate (adjOR 0.25, 95%CI 0.07–0.88), were significantly associated with PPV use (all FDR < 0.05). These associations were consistent with serum glutathione-related metabolites. The nasopharyngeal glutathione-related metabolite signature was also associated with a significantly higher risk of asthma (adjOR 0.90, 95%CI 0.82–0.99, p = 0.04). In infants hospitalized for bronchiolitis, glutathione-related metabolites were associated with bronchiolitis severity and asthma risk.

The HeMoVal study protocol: a prospective international multicenter cohort study to validate cerebrospinal fluid hemoglobin as a monitoring biomarker for aneurysmal subarachnoid hemorrhage related secondary brain injury

IntroductionPreclinical studies provided a strong rationale for a pathophysiological link between cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) and secondary brain injury after subarachnoid hemorrhage (SAH-SBI). In a single-center prospective observational clinical study, external ventricular drain (EVD) based CSF-Hb proved to be a promising biomarker to monitor for SAH-SBI. The primary objective of the HeMoVal study is to prospectively validate the association between EVD based CSF-Hb and SAH-SBI during the first 14 days post-SAH. Secondary objectives include the assessment of the discrimination ability of EVD based CSF-Hb for SAH-SBI and the definition of a clinically relevant range of EVD based CSF-Hb toxicity. In addition, lumbar drain (LD) based CSF-Hb will be assessed for its association with and discrimination ability for SAH-SBI.MethodsHeMoVal is a prospective international multicenter observational cohort study. Adult patients admitted with aneurysmal subarachnoid hemorrhage (aSAH) are eligible. While all patients with aSAH are included, we target a sample size of 250 patients with EVD within the first 14 day after aSAH. Epidemiologic and disease-specific baseline measures are assessed at the time of study inclusion. In patients with EVD or LD, each day during the first 14 days post-SAH, 2 ml of CSF will be sampled in the morning, followed by assessment of the patients for SAH-SBI, co-interventions, and complications in the afternoon. After 3 months, a clinical follow-up will be performed. For statistical analysis, the cohort will be stratified into an EVD, LD and full cohort. The primary analysis will quantify the strength of association between EVD based CSF-Hb and SAH-SBI in the EVD cohort based on a generalized additive model. Secondary analyses include the strength of association between LD based CSF-Hb and SAH-SBI in the LD cohort based on a generalized additive model, as well as the discrimination ability of CSF-Hb for SAH-SBI based on receiver operating characteristic (ROC) analyses.DiscussionWe hypothesize that this study will validate the value of CSF-Hb as a biomarker to monitor for SAH-SBI. In addition, the results of this study will provide the potential base to define an intervention threshold for future studies targeting CSF-Hb toxicity after aSAH.Study registrationClinicalTrials.gov Identifier NCT04998370. Date of registration: August 10, 2021.

SARS-CoV-2 Genomic Characteristics and Clinical Impact of SARS-CoV-2 Viral Diversity in Critically Ill COVID-19 Patients: A Prospective Multicenter Cohort Study.

The SARS-CoV-2 variant of concern, α, spread worldwide at the beginning of 2021. It was suggested that this variant was associated with a higher risk of mortality than other variants. We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 and unravel the relationships between specific viral mutations/mutational patterns and clinical outcomes. This is a prospective multicenter observational cohort study. Patients aged ≥18 years admitted to 11 intensive care units (ICUs) in hospitals in the Greater Paris area for SARS-CoV-2 infection and acute respiratory failure between 1 October 2020 and 30 May 2021 were included. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq). In total, 413 patients were included, 183 (44.3%) were infected with pre-existing variants, 197 (47.7%) were infected with variant α, and 33 (8.0%) were infected with other variants. The patients infected with pre-existing variants were significantly older (64.9 ± 11.9 vs. 60.5 ± 11.8 years; p = 0.0005) and had more frequent COPD (11.5% vs. 4.1%; p = 0.009) and higher SOFA scores (4 [3–8] vs. 3 [2–4]; 0.0002). The day-28 mortality was no different between the patients infected with pre-existing, α, or other variants (31.1% vs. 26.2% vs. 30.3%; p = 0.550). There was no association between day-28 mortality and specific variants or the presence of specific mutations. At ICU admission, the patients infected with pre-existing variants had a different clinical presentation from those infected with variant α, but mortality did not differ between these groups. There was no association between specific variants or SARS-CoV-2 genome mutational pattern and day-28 mortality.

Comparison of diagnostic criteria for acute kidney injury in critically ill children: a multicenter cohort study

BackgroundSubstantial interstudy heterogeneity exists in defining acute kidney injury (AKI) and baseline serum creatinine (SCr). This study assessed AKI incidence and its association with pediatric intensive care unit (PICU) mortality under different AKI and baseline SCr definitions to determine the preferable approach for diagnosing pediatric AKI.MethodsIn this multicenter prospective observational cohort study, AKI was defined and staged according to the Kidney Disease: Improving Global Outcome (KDIGO), modified KDIGO, and pediatric reference change value optimized for AKI (pROCK) definitions. The baseline SCr was calculated based on the Schwartz formula or estimated as the upper normative value (NormsMax), admission SCr (AdmSCr) and modified AdmSCr. The impacts of different AKI definitions and baseline SCr estimation methods on AKI incidence, severity distribution and AKI outcome were evaluated.ResultsDifferent AKI definitions and baseline SCr estimates led to differences in AKI incidence, from 6.8 to 25.7%; patients with AKI across all definitions had higher PICU mortality ranged from 19.0 to 35.4%. A higher AKI incidence (25.7%) but lower mortality (19.0%) was observed based on the Schwartz according to the KDIGO definition, which however was overcome by modified KDIGO (AKI incidence: 16.3%, PICU mortality: 26.1%). Furthermore, for the modified KDIGO, the consistencies of AKI stages between different baseline SCr estimation methods were all strong with the concordance rates > 90.0% and weighted kappa values > 0.8, and PICU mortality increased pursuant to staging based on the Schwartz. When the NormsMax was used, the KDIGO and modified KDIGO led to an identical AKI incidence (13.6%), but PICU mortality did not differ among AKI stages. For the pROCK, PICU mortality did not increase pursuant to staging and AKI stage 3 was not associated with mortality after adjustment for confounders.ConclusionsThe AKI incidence and staging vary depending on the definition and baseline SCr estimation method used. The modified KDIGO definition based on the Schwartz method leads AKI to be highly relevant to PICU mortality, suggesting that it may be the preferable approach for diagnosing AKI in critically ill children and provides promise for improving clinicians’ ability to diagnose pediatric AKI.

A nationwide prospective multicenter study of external ventricular drainage: accuracy, safety, and related complications.

External ventricular drainage (EVD) catheters are associated with complications such as EVD catheter infection (ECI), intracranial hemorrhage (ICH), and suboptimal placement. The aim of this study was to investigate the rates of EVD catheter complications and their associated risk factor profiles in order to optimize the safety and accuracy of catheter insertion. A total of 348 patients with urgently placed EVD catheters were included as a part of a prospective multicenter observational cohort. Strict definitions were applied for each complication category. The rates of misplacement, ECI/ventriculitis, and ICH were 38.6%, 12.2%, and 9.2%, respectively. Catheter misplacement was associated with midline shift (p = 0.002), operator experience (p = 0.031), and intracranial length (p < 0.001). Although mostly asymptomatic, ICH occurred more often in patients receiving prophylactic low-molecular-weight heparin (LMWH) (p = 0.002) and those who required catheter replacement (p = 0.026). Infectious complications (ECI/ventriculitis and suspected ECI) occurred more commonly in patients whose catheters were inserted at the bedside (p = 0.004) and those with smaller incisions (≤ 1 cm) (p < 0.001). ECI/ventriculitis was not associated with preinsertion antibiotic prophylaxis (p = 0.421), catheter replacement (p = 0.118), and catheter tunneling length (p = 0.782). EVD-associated complications are common. These results suggest that the operating room setting can help reduce the risk of infection, but not the use of preoperative antibiotic prophylaxis. Although EVD-related ICH was associated with LMWH prophylaxis for deep vein thrombosis, there were no significant clinical manifestations in the majority of patients. Catheter misplacement was associated with operator level of training and midline shift. Information from this multicenter prospective cohort can be utilized to increase the safety profile of this common neurosurgical procedure.

P-333 The influence of hormonal stimulation on uterine peristalsis measured by ultrasound speckle tracking in women with IVF/ICSI treatment compared to normal ovulating women

Abstract Study question To investigate possible effects of ovarian stimulation during IVF/ICSI on uterine peristalsis features using ultrasound speckle tracking compared to normal ovulating women. Summary answer Patients with a normal uterus treated with exogenous hormones during IVF/ICSI treatment show significantly increased contraction amplitude and power parameters compared to normal ovulating women. What is known already Uterine peristalsis plays a role in procreation. Subjective visual inspection of uterine peristalsis is extensively researched throughout the menstrual cycle. Studies on uterine peristalsis in IVF/ICSI patients show higher frequency of uterine contractions during the periovulatory phase. Recently, a new automated quantitative method was validated to objectively analyse uterine strain using speckle tracking. Besides objective insight in frequency, also information on amplitude, power and coordination of motion is available. The effect of exogenous hormones on uterine contraction features has not objectively been studied using this new method. Study design, size, duration This multicentre prospective observational cohort study was performed between 2020 and 2022 in the Catharina Hospital in Eindhoven, the Netherlands, Embryolab Fertility Centre in Thessaloniki, Greece and University of Naples, Federico II in Naples, Italy. 30 normal ovulating patients served as controls. The primary outcomes were the contraction features frequency, amplitude, direction, velocity, power and coordination in women undergoing IVF/ICSI on the day of follicle aspiration compared to controls on cycle day 9 – 14. Participants/materials, setting, methods 19 women undergoing IVF/ICSI were included regardless of the treatment cycle number and stimulation protocol. Indication for IVF/ICSI treatment was male subfertility (n = 8), idiopathic subfertility (n = 5), tubal factor (n = 2), primary ovarian insufficiency (n = 2) or combined (n = 2), all women had normal uteri on transvaginal ultrasound. The control group consisted of 30 healthy pre-menopausal women with normal uteri on ultrasound and spontaneous regular cycles. Main results and the role of chance Each patient underwent a 2.5 – 4 minute transvaginal ultrasound of the uterus in mid-sagittal plane. The various contraction features were extracted using a quantitative dedicated speckle tracking algorithm analysis studying motion of the subendometrial junctional zone. Mean age of IVF/ICSI patients was 32.7 years and mean BMI was 25.6. Mean age of healthy controls was 33.8 years, BMI was 23.4, and cycle length was 27.44 days. Characteristics of IVF/ICSI patients and healthy volunteers showed no statistically significant differences. Both groups predominantly consisted of nulliparous women. In IVF/ICSI patients the contraction amplitude was significantly higher compared to controls (0.062 vs 0.040; p &amp;lt; 0.001). The contraction power (combination of amplitude and frequency) appeared to be significantly higher in IVF/ICSI patients compared to controls (1528.18 vs 683.44; p &amp;lt; 0.001). No significant differences were found in contraction frequency and coordination. Even though the mean coordination did not show statistically significant differences, the values were less scattered in IVF/ICSI patients, with a much smaller range of coordination values (1.04 – 3.06) compared to healthy volunteers (1.02 – 50.33). Limitations, reasons for caution The reported difference between IVF/ICSI patients and controls in contraction amplitude and power may not solely be attributed to the administration of exogenous hormones. The difference may also be due to an underlying cause for infertility in these patients. Another limitation of this study is the small sample size. Wider implications of the findings Future research should explore which uterine contraction profile is associated with viable pregnancy: during the natural menstrual cycle, or when treated with hormones. The question arises whether it is preferred to transfer the embryo in the stimulated cycle or implement a freeze-all policy and transfer during the natural menstrual cycle. Trial registration number NCT02310802

Different Clinical Presentations of Human Rhinovirus Species Infection in Children and Adults in Mexico.

BackgroundHuman rhinoviruses (HRVs) are a common cause of influenza-like illness, with the ability to infect the upper and lower respiratory tracts. In this study we aim to describe the clinical and molecular features of HRV infection in Mexican children and adults.MethodsWe performed a hospital-based, 4-year multicenter prospective observational cohort study of patients with influenza-like illness. Participants who tested positive for HRV were included. We described demographic, clinical, and laboratory characteristics and the association between HRV types, illness severity, and clinical outcomes.ResultsOf the 5662 subjects recruited, 1473 (26%) had HRV; of those, 988 (67.1%) were adults (≥18 years) and 485 (32.9%) were children. One hundred sixty-seven (11.33%) samples were sequenced; 101 (60.5%) were rhinovirus species A (HRV-A), 22 (13.2%) were rhinovirus species B (HRV-B), and 44 (26.3%) were rhinovirus species C (HRV-C). Among children and adults, 30.5% and 23.5%, respectively, were hospitalized (non–intensive care unit [ICU]). The odds of HRV-C are higher than HRV-A for participants in the ICU (compared to outpatient) and when platelets, lymphocytes, white blood cells, and lactate dehydrogenase are increased. The odds of HRV-C are higher than HRV-A and HRV-B with shortness of breath. The odds of HRV-A are higher than HRV-B, and the odds of HRV-B are higher than HRV-C, when mild symptoms like muscle ache and headache occur.ConclusionsRhinoviruses are a common cause of influenza-like illness. It is necessary to improve the surveillance, testing, and species identification for these viruses to understand different clinical presentations and risk factors associated with worse outcomes. Clinical Trials Registration. NCT01418287.

A prospective cohort study to evaluate continuous wound infusion with local analgesics within an enhanced recovery protocol after colorectal cancer surgery.

To reduce detrimental opioid-related side effects, minimising the postoperative opioid consumption is needed, especially in older patients. Continuous wound infusion (CWI) with local analgesics appears to be an effective opioid-sparing alternative. However, the added value of CWI to an enhanced recovery protocol after colorectal cancer (CRC) surgery is unclear. The aim of this study was to evaluate the outcomes of CWI after CRC surgery within a strictly adhered to enhanced recovery protocol. In this multicentre prospective observational cohort study, patients who underwent CRC surgery between May 2019 and January 2021 were included. Patients were treated with CWI as adjunct to multimodal pain management within an enhanced recovery protocol. Postoperative opioid consumption, pain scores and outcomes regarding functional recovery were evaluated. A cohort of 130 consecutive patients were included, of whom 36.2% were ≥75 years. Postoperative opioids were consumed by 80 (61.5%) patients on postoperative day 0, and by 28 (21.5%), 27 (20.8%), and 18 (13.8%) patients on postoperative days 1, 2, and 3, respectively. Median pain scores were <4 on all days. The median time until first passage of stool was 1.0 (IQR: 1.0-2.0) day. Postoperative delirium occurred in 0.8%. Median length of hospital stay was 3.0 days (IQR: 2.0-5.0). In patients treated with CWI, low amounts of postoperative opioid consumption, adequate postoperative pain control, and enhanced recovery were observed. CWI seems a beneficial opioid-sparing alternative and may further improve the outcomes of an enhanced recovery protocol after CRC surgery, which seems especially valuable for older patients.