Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Aflibercept, ranibizumab and bevacizumab upcoming biosimilars: a general overview

: Anti-vascular endothelial growth factors currently are the first-line treatment option for neovascular age-related macular degeneration (nAMD) and other retinal vascular disorders, and their clinical use is associated with high financial burden. Biosimilars are a type of biological product highly similar to referral biologic drugs; they are increasing competition among biologics and have the potential to reduce the overall expenditures on biologics. In this comprehensive literature review, the current investigational biosimilars acting on retinal diseases are discussed. The authors review the results of clinical studies and highlight ongoing trials. Several biosimilar candidates are under evaluation and the pipeline will rapidly change in the future, as soon as each patent expires. Clinicians have to know these new therapeutic agents, which might come in the mainstream clinical practice as a more cost-efficient option

The co-administration of telaprevir increases ribavirin plasma and intra-erythrocytic concentrations, causing higher onset of anemia

Introduction: The new standard of care (SOC) for treatment of HCV-1 is the association of Telaprevir (TEL) or Boceprevir (BOC) to Ribavirin (RBV) and Peg-Interferon alfa. Despite the improved efficacy, a higher frequency of hemolytic anemia was observed. Anemia is a typical side effect of RBV. Aim: Our aim was to investigate the existence of a concentration-dependent interaction between TEL and RBV. Materials and methods: To evaluate this possible interaction 17 patients treated with SOC were compared to 119 with dual therapy. Moreover, the same comparison was performed in a sub-group of 9 out of 17 patientswhowere treated 1-2 years before with dual therapy, and recently re-treated with SOC. This comparison provided data without interferences due to the inter-patient variability. RBV plasma and intra-erythrocytic levels and TEL (\u2013S and \u2013R isomers) plasma concentrations were determined after 4 weeks of therapy with validated chromatographic methods. Results: No significant differences in weight-based dose of RBV were observed between therapies. In the 9 patients sub-group, both RBV plasma and intra-erythrocytic concentrations were significantly higher during retreatment (p = 0.015 and p = 0.012, respectively). This evidence was confirmed for intra-erythrocytic concentrations in the overall treated patients (p = 0.040). Triple therapy treated patients showed a higher incidence of anemia (88% vs. 37%, p < 0.001). Interestingly, a significant correlation (p = 0.023) emerged between hemoglobin drop andRBVplasma concentration. Moreover, RBV and TEL-S plasma concentrations were significantly (p = 0.008) correlated. Conclusions: The co-administration of TEL increased RBV concentrations in a concentration-dependent manner, leading to a higher incidence of anemia. This unbiased evidence highlights the need of specific cut-off values for RBV and TEL-S concentrations. These evidences justify the use of Therapeutic Drug Monitoring (TDM) to manage toxicity, guiding the \u201congoing\u201d dose modification to maintain patients on therapy

A new mathematical model for profiled-HFR

none14noneColì L; Ursino M; Magosso E; Capriotti P; Donati G; Cianciolo G; Panicali L; Ruggeri G; Nastasi V; Piccari M; Di Nicolò P; Cannarile D; Bergamini C; Stefoni SColì L; Ursino M; Magosso E; Capriotti P; Donati G; Cianciolo G; Panicali L; Ruggeri G; Nastasi V; Piccari M; Di Nicolò P; Cannarile D; Bergamini C; Stefoni

Confronto tra MDRD e CKD-EPI con il metodo di Bland-Altman e la regressione polinomiale frazionaria

INTRODUZIONE. Le stime del VFG ottenute con le formule MDRD e CKD-EPI forniscono risultati discrepanti. Una tecnica usata per il confronto tra le formule \ue8 il metodo di Bland-Altman, che consiste nel rappresentare graficamente sugli assi cartesiani la media delle formule e la differenza tra gli stessi due valori. I limiti di concordanza al 95% tra le formule vengono stimati come la media delle differenze \ub1 1,96 volte la deviazione standard delle differenze. Questo approccio si basa sull\u2019assunto che media e deviazione standard delle differenze siano costanti lungo tutto l\u2019asse delle ascisse. Scopo di questo studio \ue8 proporre un metodo alternativo per il calcolo dei limiti di concordanza tra MDRD e CKD-EPI, basato sulla regressione polinomiale frazionaria. MATERIALI E METODI. La popolazione considerata proviene dal registro PIRP (Prevenzione Insufficienza Renale Progressiva), che comprende i pazienti con insufficienza renale cronica afferenti a 13 Centri Nefrologici della Regione Emilia-Romagna. Per i 10.687 pazienti selezionati si \ue8 stimato il VFG utilizzando l\u2019MDRD e il CKD-EPI, ed \ue8 poi stato esaminato il grado di concordanza tra le formule con il metodo di Bland-Altman. \uc8 stata quindi utilizzata la regressione polinomiale frazionaria per esprimere la differenza tra CKD-EPI ed MDRD in funzione della media delle due formule. RISULTATI E CONCLUSIONI. La concordanza tra MDRD e CKD-EPI diminuisce all\u2019aumentare del VFG. Per un VFG medio di 10 mL/min/1,73m\ub2, la differenza tra le formule \ue8 inferiore a 1 mL/min/1,73m\ub2 nel 95% dei casi; per un VFG di 90 la differenza tra i limiti di accordo \ue8 pari, invece, a 16 mL/min/1,73m\ub2. In sintesi, per valori di VFG da 40 a 10 mL/min pu\uf2 essere indifferente utilizzare l\u2019una o l\u2019altra formula, poich\ue9 il grado di accordo tra le due formule \ue8 accettabile. Viceversa, per i pazienti con CKD agli stadi iniziali (CKD2, CKD3), si suggerisce di monitorare l\u2019andamento nel tempo della funzione renale sempre con la stessa formula di stima, poich\ue9 lo scostamento tra i valori ottenuti \ue8 abbastanza rilevante

Appendicitis risk prediction models in children presenting with right iliac fossa pain (RIFT study): a prospective, multicentre validation study.

Background Acute appendicitis is the most common surgical emergency in children. Differentiation of acute appendicitis from conditions that do not require operative management can be challenging in children. This study aimed to identify the optimum risk prediction model to stratify acute appendicitis risk in children. Methods We did a rapid review to identify acute appendicitis risk prediction models. A prospective, multicentre cohort study was then done to evaluate performance of these models. Children (aged 5\u201315 years) presenting with acute right iliac fossa pain in the UK and Ireland were included. For each model, score cutoff thresholds were systematically varied to identify the best achievable specificity while maintaining a failure rate (ie, proportion of patients identified as low risk who had acute appendicitis) less than 5%. The normal appendicectomy rate was the proportion of resected appendixes found to be normal on histopathological examination. Findings 15 risk prediction models were identified that could be assessed. The cohort study enrolled 1827 children from 139 centres, of whom 630 (34\ub75%) underwent appendicectomy. The normal appendicectomy rate was 15\ub79% (100 of 630 patients). The Shera score was the best performing model, with an area under the curve of 0\ub784 (95% CI 0\ub782\u20130\ub786). Applying score cutoffs of 3 points or lower for children aged 5\u201310 years and girls aged 11\u201315 years, and 2 points or lower for boys aged 11\u201315 years, the failure rate was 3\ub73% (95% CI 2\ub70\u20135\ub72; 18 of 539 patients), specificity was 44\ub73% (95% CI 41\ub74\u201347\ub72; 521 of 1176), and positive predictive value was 41\ub74% (38\ub75\u201344\ub74; 463 of 1118). Positive predictive value for the Shera score with a cutoff of 6 points or lower (72\ub76%, 67\ub74\u201377\ub74) was similar to that of ultrasound scan (75\ub70%, 65\ub73\u201383\ub71). Interpretation The Shera score has the potential to identify a large group of children at low risk of acute appendicitis who could be considered for early discharge. Risk scoring does not identify children who should proceed directly to surgery. Medium-risk and high-risk children should undergo routine preoperative ultrasound imaging by operators trained to assess for acute appendicitis, and MRI or low-dose CT if uncertainty remains. Funding None

The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE Registry

Background: Venous thromboembolism (VTE) is a major health problem, with over one million events every year in Europe. However, there is a paucity of data on the current management in real life, including factors influencing treatment pathways, patient satisfaction, quality of life (QoL), and utilization of health care resources and the corresponding costs. The PREFER in VTE registry has been designed to address this and to understand medical care and needs as well as potential gaps for improvement. Methods/design: The PREFER in VTE registry was a prospective, observational, multicenter study conducted in seven European countries including Austria, France Germany, Italy, Spain, Switzerland, and the UK to assess the characteristics and the management of patients with VTE, the use of health care resources, and to provide data to estimate the costs for 12 months treatment following a first-time and/or recurrent VTE diagnosed in hospitals or specialized or primary care centers. In addition, existing anticoagulant treatment patterns, patient pathways, clinical outcomes, treatment satisfaction, and health related QoL were documented. The centers were chosen to reflect the care environment in which patients with VTE are managed in each of the participating countries. Patients were eligible to be enrolled into the registry if they were at least 18 years old, had a symptomatic, objectively confirmed first time or recurrent acute VTE defined as either distal or proximal deep vein thrombosis, pulmonary embolism or both. After the baseline visit at the time of the acute VTE event, further follow-up documentations occurred at 1, 3, 6 and 12 months. Follow-up data was collected by either routinely scheduled visits or by telephone calls. Results: Overall, 381 centers participated, which enrolled 3,545 patients during an observational period of 1 year. Conclusion: The PREFER in VTE registry will provide valuable insights into the characteristics of patients with VTE and their acute and mid-term management, as well as into drug utilization and the use of health care resources in acute first-time and/or recurrent VTE across Europe in clinical practice. Trial registration: Registered in DRKS register, ID number: DRKS0000479

Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data: an observational, multicohort, retrospective analysis

International audienceTwo acute respiratory distress syndrome (ARDS) subphenotypes (hyperinflammatory and hypoinflammatory) with distinct clinical and biological features and differential treatment responses have been identified using latent class analysis (LCA) in seven individual cohorts. To facilitate bedside identification of subphenotypes, clinical classifier models using readily available clinical variables have been described in four randomised controlled trials. We aimed to assess the performance of these models in observational cohorts of ARDS. Methods: In this observational, multicohort, retrospective study, we validated two machine-learning clinical classifier models for assigning ARDS subphenotypes in two observational cohorts of patients with ARDS: Early Assessment of Renal and Lung Injury (EARLI; n=335) and Validating Acute Lung Injury Markers for Diagnosis (VALID; n=452), with LCA-derived subphenotypes as the gold standard. The primary model comprised only vital signs and laboratory variables, and the secondary model comprised all predictors in the primary model, with the addition of ventilatory variables and demographics. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUC) and calibration plots, and assigning subphenotypes using a probability cutoff value of 0·5 to determine sensitivity, specificity, and accuracy of the assignments. We also assessed the performance of the primary model in EARLI using data automatically extracted from an electronic health record (EHR; EHR-derived EARLI cohort). In Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE; n=2813), a multinational, observational ARDS cohort, we applied a custom classifier model (with fewer variables than the primary model) to determine the prognostic value of the subphenotypes and tested their interaction with the positive end-expiratory pressure (PEEP) strategy, with 90-day mortality as the dependent variable. Findings: The primary clinical classifier model had an area under receiver operating characteristic curve (AUC) of 0·92 (95% CI 0·90–0·95) in EARLI and 0·88 (0·84–0·91) in VALID. Performance of the primary model was similar when using exclusively EHR-derived predictors compared with manually curated predictors (AUC=0·88 [95% CI 0·81–0·94] vs 0·92 [0·88–0·97]). In LUNG SAFE, 90-day mortality was higher in patients assigned the hyperinflammatory subphenotype than in those with the hypoinflammatory phenotype (414 [57%] of 725 vs 694 [33%] of 2088; p<0·0001). There was a significant treatment interaction with PEEP strategy and ARDS subphenotype (p=0·041), with lower 90-day mortality in the high PEEP group of patients with the hyperinflammatory subphenotype (hyperinflammatory subphenotype: 169 [54%] of 313 patients in the high PEEP group vs 127 [62%] of 205 patients in the low PEEP group; hypoinflammatory subphenotype: 231 [34%] of 675 patients in the high PEEP group vs 233 [32%] of 734 patients in the low PEEP group). Interpretation: Classifier models using clinical variables alone can accurately assign ARDS subphenotypes in observational cohorts. Application of these models can provide valuable prognostic information and could inform management strategies for personalised treatment, including application of PEEP, once prospectively validated. Funding: US National Institutes of Health and European Society of Intensive Care Medicine