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Alternative water disinfectants to chlorination need to be identified because its effectiveness is limited by water pH and potentially carcinogen by−products resulted from chlorination and organic compound reaction. The first study aimed to evaluate the effect of different drinking water chemical disinfection treatments on water quality, its potential hazard effects on animal health, water and feed consumption, and apparent total tract digestibility in dairy beef bulls fed high-concentrate diets. For 224 days, 24 Holstein bulls (176 ± 16.3 kg BW, and 149 ± 5.8 days of age) were individually assigned to one of four treatments with different drinking water chemical disinfectants: without disinfection (CTR); acidification and chlorination (ACCHL; 0.65 mL/L H3PO4 and 0.14 mL/L NaClO 15%); hydrogen peroxide (PER; 0.15 mL/L); and chlorine dioxide (DIO; 2.50 mL/L). Data were analysed with a mixed-effects model. Treatments affected the chemical characteristics of the water: in ACCHL, pH was 6.60 and free residual chlorine was 0.75 mg/L; in PER, H2O2 was 10.6 mg/L; and in DIO, ClO2 was 0.52 mg/L. Water physicochemical quality parameters in all treatments were below maximal thresholds established for safe water consumption by the Water Safety Royal Decree (RD 140/2003). In addition, the total coliform count of treated waters was reduced (P = 0.01) compared with CTR; moreover, ACCHL and DIO treatments were more effective in reducing total coliform count than PER. Dry matter intake tended (P = 0.07) to increase in DIO compared with CTR. Treatments did not affect blood parameters nor apparent total tract digestibility. The second study aimed to evaluate the potential benefit on animal performance of two drinking water disinfectants under commercial conditions in dairy beef crossbred Holstein bulls fed high-concentrate diets. Ninety-six animals (307 ± 4.4 kg BW, and 224 ± 1.8 days of age) were allocated to six pens for 140 days and assigned to one of two treatments: ACCHL, most common water disinfectant, and DIO. Data were analysed with a mixed-effects model. Water total coliform count and water consumption were similar between treatments. Concentrate intake was greater (P = 0.02) in ACCHL for the last 14 study days. Growth performance and carcass quality were similar between treatments. In summary, acidification and chlorination, H2O2, and ClO2 as drinking water disinfectants in dairy beef bulls had good disinfecting activity without detrimental effects on health and nutrient digestibility, and performance.

The error-related negativity and an N2-component recorded over medial frontal cortex index core functions of cognitive control. While they are known to originate from agranular frontal areas, the underlying microcircuit mechanisms remain elusive. Most insights about microcircuit function have been derived from variations of the so-called canonical microcircuit model. These microcircuit architectures are based extensively on studies from granular sensory cortical areas in monkeys, cats, and rodents. However, evidence has shown striking cytoarchitectonic differences across species and differences in the functional relationships across cortical layers in agranular compared to granular sensory areas. In this minireview, we outline a tentative microcircuit model underlying cognitive control in the agranular frontal cortex of primates. The model incorporates the main GABAergic interneuron subclasses with specific laminar arrangements and target regions on pyramidal cells. We emphasize the role of layer 5 pyramidal cells in error and conflict detection. We offer several specific questions necessary for creating a specific intrinsic microcircuit model of the agranular frontal cortex.

Objective: To analyze if the implementation of a multidisciplinary extracorporeal cardiopulmonary resuscitation (ECPR) program in a tertiary hospital in Spain is feasible and could yield survival outcomes similar to international published experiences., Design: Retrospective observational cohort study., Setting: One tertiary referral university hospital in Spain., Patients: All adult patients receiving ECPR between January 2019 and April 2023., Interventions: Prospective collection of variables and follow-up for up to 180 days., Main Variables of Interest: To assess outcomes, survival with good neurological outcome defined as a Cerebral Performance Categories scale 1-2 at 180 days was used. Secondary variables were collected including demographics and comorbidities, cardiac arrest and cannulation characteristics, ROSC, ECMO-related complications, survival to ECMO decannulation, survival at Intensive Care Unit (ICU) discharge, survival at 180 days, neurological outcome, cause of death and eligibility for organ donation., Results: Fifty-four patients received ECPR, 29 for OHCA and 25 for IHCA. Initial shockable rhythm was identified in 27 (50%) patients. The most common cause for cardiac arrest was acute coronary syndrome [29 (53.7%)] followed by pulmonary embolism [7 (13%)] and accidental hypothermia [5 (9.3%)]. Sixteen (29.6%) patients were alive at 180 days, 15 with good neurological outcome. Ten deceased patients (30.3%) became organ donors after neuroprognostication., Conclusions: The implementation of a multidisciplinary ECPR program in an experienced Extracorporeal Membrane Oxygenation center in Spain is feasible and can lead to good survival outcomes and valid organ donors., (Copyright © 2024 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Purpose of Review: Machine learning (ML), a subset of artificial intelligence (AI), has been vital in advancing tasks such as image classification and speech recognition. Its integration into clinical medicine, particularly dermatology, offers a significant leap in healthcare delivery., Recent Findings: This review examines the impact of ML on psoriasis-a condition heavily reliant on visual assessments for diagnosis and treatment. The review highlights five areas where ML is reshaping psoriasis care: diagnosis of psoriasis through clinical and dermoscopic images, skin severity quantification, psoriasis biomarker identification, precision medicine enhancement, and AI-driven education strategies. These advancements promise to improve patient outcomes, especially in regions lacking specialist care. However, the success of AI in dermatology hinges on dermatologists' oversight to ensure that ML's potential is fully realized in patient care, preserving the essential human element in medicine., Summary: This collaboration between AI and human expertise could define the future of dermatological treatments, making personalized care more accessible and precise., Competing Interests: Conflict of Interest The authors declare no conflict of interest.

Alternative water disinfectants to chlorination need to be identified because its effectiveness is limited by water pH and potentially carcinogen by-products resulted from chlorination and organic compound reaction. The first study aimed to evaluate the effect of different drinking water chemical disinfection treatments on water quality, its potential hazard effects on animal health, water and feed consumption, and apparent total tract digestibility in dairy beef bulls fed high-concentrate diets. For 224 days, 24 Holstein bulls (176 ± 16.3 kg BW, and 149 ± 5.8 days of age) were individually assigned to one of four treatments with different drinking water chemical disinfectants: without disinfection (CTR); acidification and chlorination (ACCHL; 0.65 mL/L H 3 PO 4 and 0.14 mL/L NaClO 15%); hydrogen peroxide (PER; 0.15 mL/L); and chlorine dioxide (DIO; 2.50 mL/L). Data were analysed with a mixed-effects model. Treatments affected the chemical characteristics of the water: in ACCHL, pH was 6.60 and free residual chlorine was 0.75 mg/L; in PER, H 2 O 2 was 10.6 mg/L; and in DIO, ClO 2 was 0.52 mg/L. Water physicochemical quality parameters in all treatments were below maximal thresholds established for safe water consumption by the Water Safety Royal Decree (RD 140/2003). In addition, the total coliform count of treated waters was reduced (P = 0.01) compared with CTR; moreover, ACCHL and DIO treatments were more effective in reducing total coliform count than PER. Dry matter intake tended (P = 0.07) to increase in DIO compared with CTR. Treatments did not affect blood parameters nor apparent total tract digestibility. The second study aimed to evaluate the potential benefit on animal performance of two drinking water disinfectants under commercial conditions in dairy beef crossbred Holstein bulls fed high-concentrate diets. Ninety-six animals (307 ± 4.4 kg BW, and 224 ± 1.8 days of age) were allocated to six pens for 140 days and assigned to one of two treatments: ACCHL, most common water disinfectant, and DIO. Data were analysed with a mixed-effects model. Water total coliform count and water consumption were similar between treatments. Concentrate intake was greater (P = 0.02) in ACCHL for the last 14 study days. Growth performance and carcass quality were similar between treatments. In summary, acidification and chlorination, H 2 O 2 , and ClO 2 as drinking water disinfectants in dairy beef bulls had good disinfecting activity without detrimental effects on health and nutrient digestibility, and performance., (Copyright © 2024. Published by Elsevier B.V.)

Background: Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation., Objective: To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting., Methods: We studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed., Results: A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83-0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes., Conclusion: We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis., (© 2024 European Academy of Dermatology and Venereology.)

Within patients with sepsis, there exists significant heterogeneity, and while all patients should receive conventional therapy, there are subgroups of patients who may benefit from specific therapies, often referred to as rescue therapies. Therefore, the identification of these specific patient subgroups is crucial and lays the groundwork for the application of precision medicine based on the development of targeted interventions. Over the years, efforts have been made to categorize sepsis into different subtypes based on clinical characteristics, biomarkers, or underlying mechanisms. For example, sepsis can be stratified into different phenotypes based on the predominant dysregulated host response. These phenotypes can range from hyperinflammatory states to immunosuppressive states and even mixed phenotypes. Each phenotype may require different therapeutic approaches to improve patient outcomes. Rescue strategies for septic shock may encompass various interventions, such as immunomodulatory therapies, extracorporeal support (e.g., ECMO), or therapies targeted at specific molecular or cellular pathways involved in the pathophysiology of sepsis. In recent years, there has been growing interest in precision medicine approaches to sepsis and phenotype identification. Precision medicine aims to tailor treatments to each individual patient based on their unique characteristics and disease mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chiscano-Camón, Ruiz-Sanmartin, Bajaña, Bastidas, Lopez-Martinez, Franco-Jarava, Gonzalez, Larrosa, Riera, Nuvials-Casals, Ruiz-Rodríguez and Ferrer.)

Arthrogenic Muscle Inhibition (AMI) is a phenomenon observed in individuals with joint injury or pathology, characterized by a reflexive inhibition of surrounding musculature, altered neuromuscular control, and compromised functional performance. After anterior cruciate ligament reconstruction (ACLR) one of the most obvious consequences of AMI is the lack of quadriceps activation and strength. Understanding the underlying mechanisms of AMI is crucial for developing effective therapeutic interventions. The surgical procedure needed to reconstruct the ACL has biochemical et physiological consequences such as inflammation, pain, and altered proprioception. These alterations contribute to the development of AMI. Therapeutic interventions aimed at addressing AMI encompass a multidimensional approach targeting pain reduction, inflammation management, proprioceptive training, and quadriceps activation. Early management focusing on pain modulation through modalities like ice, compression, and pharmacological agents help mitigate the inflammatory response and alleviate pain, thereby reducing the reflexive inhibition of quadriceps. Quadriceps activation techniques such as neuromuscular electrical stimulation (NMES) and biofeedback training aid in overcoming muscle inhibition and restoring muscle strength. NMES elicits muscle contractions through electrical stimulation, bypassing the inhibitory mechanisms associated with AMI, thus facilitating muscle activation and strength gains. Comprehensive rehabilitation programs tailored to individual needs and stage of recovery are essential for optimizing outcomes in AMI. The objective of this clinical viewpoint is to delineate the significance of adopting a multimodal approach for the effective management of AMI, emphasizing the integration of pain modulation, proprioceptive training, muscle activation techniques, and manual therapy interventions. Highlighting the critical role of early intervention and targeted rehabilitation programs, this article aims to underscore their importance in restoring optimal function and mitigating long-term complications associated with AMI., (© The Author(s).)

Aims: Drug-refractory electrical storm (ES) is a life-threatening medical emergency. We describe the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in drug-refractory ES without a reversible trigger, for which specific guideline recommendations are still lacking., Methods and Results: Retrospective observational study in four Iberian centres on the indications, treatment, complications, and outcome of drug-refractory ES not associated with acute coronary syndromes, decompensated heart failure, drug toxicity, electrolyte disturbances, endocrine emergencies, concomitant acute illness with fever, or poor compliance with anti-arrhythmic drugs, requiring VA-ECMO for circulatory support. Thirty-four (6%) out of 552 patients with VA-ECMO for cardiogenic shock were included [71% men; 57 (44-62) years], 65% underwent cardiopulmonary resuscitation before VA-ECMO implantation, and 26% during cannulation. Left ventricular unloading during VA-ECMO was used in 8 (24%) patients: 3 (9%) with intraaortic balloon pump, 3 (9%) with LV vent, and 2 (6%) with Impella. Thirty (88%) had structural heart disease and 8 (24%) had an implantable cardioverter-defibrillator. The drug-refractory ES was mostly due to monomorphic ventricular tachycardia (VT) and ventricular fibrillation (VF) (59%), isolated monomorphic VT (26%), polymorphic VT (9%), or VF (6%). Thirty-one (91%) required deep sedation, 44% overdrive pacing, 36% catheter ablation, and 26% acute autonomic modulation. The main complications were nosocomial infection (47%), bleeding (24%), and limb ischaemia (21%). Eighteen (53%) were weaned from VA-ECMO, and 29% had heart transplantation. Twenty-seven (79%) survived to hospital discharge (48 (33-82) days). Non-survivors were older [62 (58-67) vs. 54 (43-58); P < 0.01] and had a higher first rhythm disorder-to-ECMO interval [0 (0-2) vs. 2 (1-11) days; P = 0.02]. Seven (20%) had rehospitalization during follow-up [29 (12-48) months], with ES recurrence in 6%., Conclusions: VA-ECMO bridged drug-refractory ES without a reversible trigger with a high success rate. This required prolonged hospital stays and coordination between the ECMO centre, the electrophysiology laboratory, and the heart transplant programme., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: In the pivotal phase III RECOURSE trial, trifluridine/tipiracil (FTD/TPI) improved progression-free and overall survival (PFS, OS) of patients with pre-treated metastatic colorectal cancer (mCRC). Subsequently, the TALLISUR trial provided post-authorisation efficacy and safety data and patient-reported outcomes on quality of life (QoL) in a German patient cohort. The present analysis reports the final data on efficacy, safety and QoL and investigates the impact of baseline characteristics and associated prognostic subgroups on outcome., Methods: In this prospective, multi-centre, Germany-wide, phase IV study, patients with pre-treated mCRC were given the choice to receive either FTD/TPI or best supportive care (BSC). To assess the primary endpoint, QoL, EORTC QLQ-C30 questionnaires were employed. Secondary endpoints included QoL assessed through EQ-5D-5L questionnaires, OS, PFS and safety. Additionally, 3 subgroups were defined according to a post-hoc analysis of the RECOURSE trial: best, good and poor prognostic characteristics (BPC, GPC, PPC). Patients with < 3 metastatic sites at inclusion and/or ≥ 18 months from diagnosis to inclusion were considered to have GPC. GPC patients without liver metastasis at inclusion were considered to have BPC. All remaining patients were considered to have PPC., Results: Of 195 patients, 186 decided to receive FTD/TPI and 9 to receive BSC. The low number of patients in the BSC-arm did not allow statistically meaningful analyses. Treatment with FTD/TPI was associated with maintained QoL. For all patients, median OS was 6.9 months (95% CI 6.1 - 8.3) and for the defined subgroups (BPC n = 20 vs GPC n = 65 vs PPC n = 121) 12.2, 7.9 and 6.8 months (95% CI 6.0 - 18.2, 6.2 - 13.3, 5.4 - 8.1). The most frequent TEAEs were neutropenia (29.6%), anaemia (24.7%) and nausea (23.7%). Febrile neutropenia occurred in 1.1%., Conclusions: Treatment of patients suffering from pre-treated mCRC with FTD/TPI was associated not only with prolonged survival and delayed progression, but also with maintained QoL. Independent of other baseline characteristics such as ECOG performance status and age, low metastatic burden and indolent disease were factors associated with favourable outcome., Clinical Trial Registration: EudraCT-Number 2017-000292-83, first registration 19/06/2017., (© 2024. The Author(s).)

We test the robustness of the self-controlled risk interval (SCRI) design in a setting where time between doses may introduce time-varying confounding, using both negative control outcomes (NCOs) and quantitative bias analysis (QBA). All vaccinated cases identified from 5 European databases between 1 September 2020 and end of data availability were included. Exposures were doses 1-3 of the Pfizer, Moderna, AstraZeneca, and Janssen COVID-19 vaccines; outcomes were myocarditis and otitis externa (NCO). The SCRI used a 60-day control window and dose-specific 28-day risk windows, stratified by vaccine brand and adjusted for calendar time. The QBA included two scenarios: (i) baseline probability of the confounder was higher in the control window and (ii) vice versa. The NCO was not associated with any of the COVID-19 vaccine types or doses except Moderna dose 1 (IRR = 1.09, 95%CI 1.01-1.09). The QBA suggested even the strongest literature-reported confounder (COVID-19; RRmyocarditis = 18.3) could only explain away part of the observed effect from IRR = 3 to IRR = 1.40. The SCRI seems robust to unmeasured confounding in the COVID-19 setting, although a strong unmeasured confounder could bias the observed effect upward. Replication of our findings for other safety signals would strengthen this conclusion., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Objective: An effective tool for establishing concordant end-of-life (EOL) care in patients with cancer is advance care planning (ACP). However, various barriers, including psychological obstacles, hamper the access to ACP. Therefore, a new conceptual model combining a psycho-oncological approach with structured ACP was developed. The effectiveness and efficiency of this new concept of collaborative ACP (col-ACP) is evaluated in the present randomised controlled trial in patients with palliative cancer., Methods: 277 patients with palliative cancer and their relatives were randomised into three groups (1) collaborative ACP (col-ACP) consisting of a psycho-oncological approach addressing barriers to EOL conversations followed by a standardised ACP procedure, (2) supportive intervention (active control) and (3) standard medical care., Results: Patients in the col-ACP group completed advance directives (p<0.01) and healthcare proxies (p<0.01) significantly more often. Additionally, they felt better planned ahead for their future treatment (p<0.01) and were significantly more confident that their relatives were aware of their treatment wishes (p=0.03). In fact, their goals of care were known and highly fulfilled. However, patients' and caregivers' quality of life, patients' stress, depression and peace did not differ between the groups., Conclusions: The new, well-received, concept of col-ACP improves readiness and access to ACP and results in more consistent EOL care. Further, even if no direct influence on quality of life could be proven, it supports patients in planning their treatment, making autonomous decisions and regaining self-efficacy in the face of life-limiting cancer. Therefore, a closer interlocking and information exchange between psycho-oncological and ACP services seems to be reasonable., Trial Registration Number: NCT03387436., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Bilevel-positive airway pressure (BiPAP) is a noninvasive respiratory support modality which reduces effort in patients with respiratory failure. However, it may increase tidal ventilation and transpulmonary pressure, potentially aggravating lung injury. We aimed to assess if the use of BiPAP before intubation was associated with increased mortality in adult patients with coronavirus disease 2019 (COVID-19) who received venovenous extracorporeal membrane oxygenation (ECMO). We used the Extracorporeal Life Support Organization Registry to analyze adult patients with COVID-19 supported with venovenous ECMO from January 1, 2020, to December 31, 2021. Patients treated with BiPAP were compared with patients who received other modalities of respiratory support or no respiratory support. A total of 9,819 patients from 421 centers were included. A total of 3,882 of them (39.5%) were treated with BiPAP before endotracheal intubation. Patients supported with BiPAP were intubated later (4.3 vs . 3.3 days, p < 0.001) and showed higher unadjusted hospital mortality (51.7% vs. 44.9%, p < 0.001). The use of BiPAP before intubation and time from hospital admission to intubation resulted as independently associated with increased hospital mortality (odds ratio [OR], 1.32 [95% confidence interval {CI}, 1.08-1.61] and 1.03 [1-1.06] per day increase). In ECMO patients with severe acute respiratory failure due to COVID-19, the extended use of BiPAP before intubation should be regarded as a risk factor for mortality., Competing Interests: Disclosure: None reported related to the present manuscript. D.B. receives research support from and consults for LivaNova. He has been on the medical advisory boards for Abiomed, Xenios, Medtronic, Inspira, and Cellenkos. He is the President-elect of the Extracorporeal Life Support Organization (ELSO) and the Chair of the Executive Committee of the International ECMO Network (ECMONet), and he writes for UpToDate. J.R. received honoraria for lecture and medical advisory from Gilead, Medtronic, and Werfen. He’s part of the ELSO Scientific Oversight Committee. A.C. reports grants and personal fees from Getinge, Xenios, and Baxter. R.P.B. is a member of the ELSO Executive Board and co-chair of PediECMO. L.B. received honoraria for a lecture from Fisher Paykel. G.B. received consulting fees from Flowmeter S.p.a. and an institutional grant from DIMAR S.r.l. The other authors have no conflicts of interest to report., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

Background and Aims: Familial inflammatory bowel disease (IBD) history is a controversial prognostic factor in IBD. We aimed to evaluate the impact of a familial history of IBD on the use of medical and surgical treatments in the biological era., Methods: Patients included in the prospectively maintained ENEIDA database and diagnosed with IBD after 2005 were included. Familial forms were defined as those cases with at least one first-degree relative diagnosed with IBD. Disease phenotype, the use of biological agents, or surgical treatments were the main outcomes., Results: A total of 5263 patients [2627 Crohn's disease (CD); 2636 ulcerative colitis (UC)] were included, with a median follow-up of 31 months. Of these, 507 (10%) corresponded to familial forms. No clinical differences were observed between familial and sporadic IBD forms except a lower age at IBD diagnosis and a higher rate of males in familial forms of UC. In CD, the proportions of patients treated with thiopurines (54.4% vs 46.7%; P = .015) and survival time free of thiopurines (P = .009) were lower in familial forms. No differences were found regarding the use of biological agents. Concerning surgery, a higher rate of intestinal resections was observed in sporadic CD (14.8% vs 9.9%, P = .027). No differences were observed in UC., Conclusions: In the era of biological therapies, familial and sporadic forms of IBD show similar phenotypes and are managed medically in a similar way; whether these is due to lack of phenotypical differences or an effect of biological therapies is uncertain. What is already known on this topic: IBD's etiopathogenesis points to an interaction between environmental and genetic factors, being familial history a controversial prognostic factor. Biological agents use and need for surgery regarding familial or sporadic forms of IBDs present conflicting results. What this study adds: Familial and sporadic forms of IBD have similar phenotypes and are managed medically and surgically in a similar way. How this study might affect research, practice or policy: Familial aggregation should not be considered a factor associated with more aggressive disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Over the past few years, venereal or sexually transmitted infections (STIs) have been on the rise worldwide requiring additional specialized monographic consultations to specifically treat STIs. Therefore, the Spanish Academy of Dermatology and Venereology (AEDV) Research Working Group on STIs and HIV has drafted this document with the necessary requirements in terms of infrastructure, personnel, technology, specific materials for sample collection, and needs for current therapeutic options. Strict emphasis is placed on the protection of patient privacy. A health care circuit model is outlined too. Additionally, a section has been included on contact tracking and reporting, key elements for the effective prevention and control of STIs. These clinical practice guidelines seek to establish a clinical action framework adapted to the current challenges posed by STIs and HIV in the dermatology, venereology, and multidisciplinary settings., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Certolizumab is an Fc-free PEGylated tumor necrosis factor-alpha (TNFα) inhibitor recently approved for the treatment of moderate-to-severe plaque psoriasis, although there is limited real-world evidence on the effectiveness and safety in patients with plaque psoriasis treated with certolizumab. The objective of this article is to determine the effectiveness, drug survival, and safety, including pregnancy, childbirth, and lactation, of certolizumab in moderate-to-severe plaque psoriasis under real-world conditions., Methods: This is a retrospective, multicenter, observational study performed in 15 hospitals in Spain. It evaluates the effectiveness and safety of certolizumab in plaque psoriasis in the clinical practice setting., Results: A total of 67 patients (73% female) were evaluated with a mean baseline Psoriasis Area Severity Index (PASI) of 8.9. At Week 12, the mean PASI was 2.3 (n = 67), 1.3 (n = 57) at Week 24 and 1.3 at Week 52 (n = 34). Absolute PASI < 3 was achieved in 69, 86, and 92% of patients at Weeks 12, 24, and 52, respectively, as observed. For its part, using the under-response imputation analysis, PASI < 3 at Weeks 12, 24, and 52 were achieved by 69, 73, and 49% of the patients, respectively. A total of 35 patients (52%) had concomitant psoriatic arthritis, and, in 24 of them, Disease Activity in Psoriatic Arthritis Score (DAPSA) was recorded at baseline, with a mean value of 17.9 which decreased to 8.2 at Week 12 (n = 22) and to 3.6 at Week 24 (n = 18). Certolizumab treatment was discontinued in 14 out of 67 patients (21%), due to lack/loss of cutaneous or articular effectiveness (n = 11) or patient decision (n = 2) or adverse event in only one patient who developed active tuberculosis. A lower baseline PASI [hazard ratio (HR): 1.12 (1.02-1.23); P = 0.023] and a more significant reduction in PASI at Week 12 [HR: 1.16 (1.07-1.27); P < 0.001] and Week 52 [HR: 1.47 (1.11-1.96); P = 0.007] was shown to be significantly related with better survival for the entire follow-up period. Fourteen patients were treated during pregnancy and/or lactation without reporting adverse events in either the patient or the newborn., Conclusions: Certolizumab consistently showed high effectiveness and drug survival rates in this real-life cohort. The safety demonstrated in clinical trials during pregnancy and lactation seems to be confirmed in clinical practice., (© 2024 the International Society of Dermatology.)

Purpose: The COVID-19 pandemic has impacted medication needs and prescribing practices, including those affecting pregnant women. Our goal was to investigate patterns of medication use among pregnant women with COVID-19, focusing on variations by trimester of infection and location., Methods: We conducted an observational study using six electronic healthcare databases from six European regions (Aragon/Spain; France; Norway; Tuscany, Italy; Valencia/Spain; and Wales/UK). The prevalence of primary care prescribing or dispensing was compared in the 30-day periods before and after a positive COVID-19 test or diagnosis., Results: The study included 294,126 pregnant women, of whom 8943 (3.0%) tested positive for, or were diagnosed with, COVID-19 during their pregnancy. A significantly higher use of antithrombotic medications was observed particularly after COVID-19 infection in the second and third trimesters. The highest increase was observed in the Valencia region where use of antithrombotic medications in the third trimester increased from 3.8% before COVID-19 to 61.9% after the infection. Increases in other countries were lower; for example, in Norway, the prevalence of antithrombotic medication use changed from around 1-2% before to around 6% after COVID-19 in the third trimester. Smaller and less consistent increases were observed in the use of other drug classes, such as antimicrobials and systemic corticosteroids., Conclusion: Our findings highlight the substantial impact of COVID-19 on primary care medication use among pregnant women, with a marked increase in the use of antithrombotic medications post-COVID-19. These results underscore the need for further research to understand the broader implications of these patterns on maternal and neonatal/fetal health outcomes., (© 2024. The Author(s).)

Introduction: Cases of myocarditis after COVID-19 messenger RNA (mRNA) vaccines administration have been reported. Although the majority follow a mild course, fulminant presentations may occur. In these cases, cardiopulmonary support with venoarterial extracorporeal membrane oxygenation (V-A ECMO) may be needed., Results: We present two cases supported with V-A ECMO for refractory cardiogenic shock due to myocarditis secondary to a mRNA SARS-CoV2 vaccine. One of the cases was admitted for out-of-hospital cardiac arrest. In both, a peripheral V-A ECMO was implanted in the cath lab using the Seldinger technique. An intra-aortic balloon pump was needed in one case for left ventricle unloading. Support could be successfully withdrawn in a mean of five days. No major bleeding or thrombosis complications occurred. Whereas an endomyocardial biopsy was performed in both, a definite microscopic diagnosis just could be reached in one of them. Treatment was the same, using 1000mg of methylprednisolone/day for three days. A cardiac magnetic resonance was performed ten days after admission, showing a significant improvement of the left ventricular ejection fraction and diffuse oedema and subepicardial contrast intake in different segments. Both cases were discharged fully recovered, with CPC 1., Conclusions: COVID-19 vaccine-associated fulminant myocarditis has a high morbidity and mortality but presents a high potential for recovery. V-A ECMO should be established in cases with refractory cardiogenic shock during the acute phase., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To determine return to running criteria currently used by physiotherapists following anterior cruciate ligament (ACL) injury., Design: Self-reported online international survey., Methods: An online survey of physiotherapists across Australia, the Netherlands and France., Results: A total of 476 respondants participated in the survey across Australia (n = 153), the Netherlands (n = 162), and France (n = 161). For return to running criteria following a non-operative approach, the majority of respondents chose swelling (40.55%, n = 193/476), pain (38.24%, n = 182/476), knee extensor strength (34.34%, n = 163/476), single leg squat (31.93%, n = 152/476) and knee flexor strength (29.83%, n = 142/476). After ACL reconstruction, the highest responses were also swelling (41.18%, n = 196/476), pain (37.18%, n = 177/476), knee extensor strength (37.18%, n = 177/476) and single leg squat (33.19%, n = 158/476). From the identified themes the most common cutoff variables were pain between 0 and 3/10, swelling < grade 1+ and limb symmetry on strength and hop tests >70 %., Conclusion: Physiotherapists in Australia, France, and the Netherlands use many different return to running criteria and most of them use more than one criterion. Despite this, there was little consensus on the cut-off physiotherapists use to apply these criteria., Competing Interests: Declaration of competing interest There are no declarations of interest for this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate the potential association between chronic exposure to medication and death related to COVID-19., Methods: This is a retrospective cross-sectional study that included all patients hospitalised due to COVID-19 from 11 March to 4 June 2020 in our centre. Chronic patient medication was classified by the Anatomical Therapeutic Chemical (ATC) classification; demographic and clinical data were analysed. Multivariate logistic regression models were used to estimate the adjusted odds ratios (aOR) of death for each drug exposure; each aOR represents an independent model adjusted by clinical factors related to COVID-19 mortality., Results: The study included 978 patients with a mean (SD) age of 64.5 (17.7) years who were predominantly male (531, 54.3%). Of all 978 patients, 182 (18.61%) died during the follow-up of the study. The most common Charlson Comorbidity Index (CCI) was 0, 4.2% were smokers, 16.7% were obese, 47.4% had hypertension, and 19.4% were diabetic. Most patients (70.8%) were prescribed at least one treatment, 32.5% used >5 treatments, and 8.6% >10. Our data suggest that COVID-19 hospitalised patients taking trimethoprim and analogues, leukotriene receptor antagonists, calcineurin inhibitors, aldosterone antagonists, selective immunosuppressants, propulsives, insulins and analogues, and benzodiazepine derivatives have a higher risk of death., Conclusions: This study investigated the association between chronic exposure to drugs and the risk of death in COVID-19 patients. Our results have shed some light on the impact of chronic drug exposure on the risk of severe COVID-19; however, further research is needed to increase the understanding about its relevance., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Precision oncology treatments are being applied more commonly in breast and gynecological oncology through the implementation of Molecular Tumor Boards (MTBs), but real-world clinical outcome data remain limited. Methods: A retrospective analysis was conducted in patients with breast cancer (BC) and gynecological malignancies referred to our center's MTB from 2018 to 2023. The analysis covered patient characteristics, next-generation sequencing (NGS) results, MTB recommendations, therapy received, and clinical outcomes. Results: Sixty-three patients (77.8%) had metastatic disease, and forty-four patients (54.3%) had previously undergone three or more lines of systemic treatment. Personalized treatment recommendations were provided to 50 patients (63.3%), while 29 (36.7%) had no actionable target. Ultimately, 23 patients (29.1%) underwent molecular-matched treatment (MMT). Commonly altered genes in patients with pan-gyn tumors (BC and gynecological malignancies) included TP53 ( n = 42/81, 51.9%), PIK3CA ( n = 18/81, 22.2%), BRCA1/2 ( n = 10/81, 12.3%), and ARID1A ( n = 9/81, 11.1%). Patients treated with MMT showed significantly prolonged progression-free survival (median PFS 5.5 vs. 3.5 months, p = 0.0014). Of all patients who underwent molecular profiling, 13.6% experienced a major clinical benefit (PFSr ≥ 1.3 and PR/SD ≥ 6 months) through precision oncology. Conclusions: NGS-guided precision oncology demonstrated improved clinical outcomes in a subgroup of patients with gynecological and breast cancers.

Background: The treatment of psoriasis in patients with a personal history of cancer is a matter of debate and limited evidence is available to guide clinicians., Objectives: To report a multicenter real-life experience of a group of patients with psoriasis undergoing treatment with guselkumab and a history of cancer., Methods: We conducted a multicenter retrospective Spanish study enrolling patients with moderate-to-severe plaque psoriasis and neoplasia being treated with guselkumab for their psoriasis., Results: Twenty patients with moderate-to-severe psoriasis and at least 12 weeks of ongoing treatment were included. For the analysis, a 52 week follow-up period was evaluated in terms of efficacy and safety. Most of the malignancies in these patients were solid tumors. The percentage of patients achieving psoriasis area and severity index ≤3 at week 12 and week 52 was 80% and 87.5%, respectively, whereas 68.8% of patients achieved psoriasis area and severity index ≤1. A 52-week survival rate of 100% in the study population was observed ( n  = 20), including those patients with concomitant active cancers ( n  = 14). No adverse effects or dropouts related to guselkumab safety profile were detected., Limitations: Modest sample size and the retrospective nature of the study., Conclusion: Guselkumab not only demonstrates high effectiveness in treating psoriasis but also exhibits a favorable safety profile in patients with neoplasms., Competing Interests: Dr Gracia Cazaña has received grants for attending congresses as well as fees for studies, lectures, presentations, courses, and consultancy from AbbVie, Almirall, Amgen, Biogen, Janssen, Lilly, Leo, Novartis, Pfizer, and UCB. Dr Yanguas has received grants for attending congresses as well as fees for studies, lectures, presentations, courses, and consultancy from AbbVie, Leo Pharma, Novartis, Janssen, Lilly, Amgen, Almirall, Pfizer, and MSD. Drs Morales Callaghan and Ara-Martín have received grants for attending congresses as well as fees for studies, lectures, presentations, courses, and consultancy from Janssen, Novartis, Lilly, AbbVie, Leo Pharma, Almirall, UCB Pharma, Sanofi, and Pfizer. Drs Riera Monroig, Izu, Lorda Espés, Sánchez Salas, García Gil, Navarro Bielsa, Aldea Manrique, Almenara Blasco, García-Latasa de Araníbar, and Fuentelsaz have no conflicts of interest to declare., (© 2024 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Background: Biological therapy dose modification is a common practice in the long-term treatment of plaque psoriasis., Objective: The objective of the study was to determine prevalence, characteristics of patients, effectiveness, treatment survival of secukinumab dose reduction (SEC-DR) strategy and assess its safety and cost implications., Methods: A retrospective, observational, multicenter cohort study was conducted in patients with plaque psoriasis treated with secukinumab and up to 2 years of follow-up., Results: In 63/347 patients with an initial standard dose regimen, SEC-DR was tried at any moment in 18.2% of them after sustained response. In 51 patients, the interval between administrations was increased while in 12 patients, monthly dose was reduced to 150 mg. Successful SEC-DR was achieved in 77.8% of the patients, with sustained PASI response to the end of the study. Survival of secukinumab treatment and safety profile were not compromised by DR. The use of DR saved 33% of the cost, including failures in which standard treatment was resumed., Limitations: The proper of the study designed and the arbitrary definition of "DR success.", Conclusion: Off-label SEC-DR strategy was used in patients with sustained response to standard dose regimen; this strategy showed long-term efficacy without compromising treatment survival or worsening the safety profile while also being cost saving., (© 2024 the International Society of Dermatology.)

Limb ischaemia is a clinically relevant complication of venoarterial extracorporeal membrane oxygenation (VA ECMO) with femoral artery cannulation. No selective distal perfusion or other advanced techniques were used in the past to maintain adequate distal limb perfusion. A more recent trend is the shift from the reactive or emergency management to the pro-active or prophylactic placement of a distal perfusion cannula to avoid or reduce limb ischaemia-related complications. Multiple alternative cannulation techniques to the distal perfusion cannula have been developed to maintain distal limb perfusion, including end-to-side grafting, external or endovascular femoro-femoral bypass, retrograde limb perfusion (e.g., via the posterior tibial, dorsalis pedis or anterior tibial artery), and, more recently, use of a bidirectional cannula. Venous congestion has also been recognized as a potential contributing factor to limb ischaemia development and specific techniques have been described with facilitated venous drainage or bilateral cannulation being the most recent, to reduce or avoid venous stasis as a contributor to impaired limb perfusion. Advances in monitoring techniques, such as near-infrared spectroscopy and duplex ultrasound analysis, have been applied to improve decision-making regarding both the monitoring and management of limb ischaemia. This narrative review describes the evolution of techniques used for distal limb perfusion during peripheral VA ECMO., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DB: receives research support from and consults for LivaNova. He has been on the medical advisory boards for Abiomed, Xenios, Medtronic, Inspira and Cellenkos. He is the President-elect of the Extracorporeal Life Support Organization (ELSO) and the Chair of the Executive Committee of the International ECMO Network (ECMONet), and he writes for UpToDate. GM: is the President of the Extracorporeal Life Support Organization (ELSO). LMB: is a member of the Medical Advisory Boards of Eurosets Srl., Medolla, Italy; Xenios AG/Fresenius, Heilbronn, Germany; and HenoCue AB, Angelholm, Sweden. RL: Member of the Medical Advisory Board for Eurosets, Hemocue, and Xenios, Consultant for Medtronic, LivaNova, CORCYM, Abiomed, and Getinge, Research Grant from Medtronic. The others declared to have no competing interests.

The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for temporary mechanical circulatory support in various clinical scenarios has been increasing consistently, despite the lack of sufficient evidence regarding its benefit and safety from adequately powered randomized controlled trials. Although the ARREST trial (Advanced Reperfusion Strategies for Patients with Out-of-Hospital Cardiac Arrest and Refractory Ventricular Fibrillation) and a secondary analysis of the PRAGUE OHCA trial (Prague Out-of-Hospital Cardiac Arrest) provided some evidence in favor of VA-ECMO in the setting of out-of-hospital cardiac arrest, the INCEPTION trial (Early Initiation of Extracorporeal Life Support in Refractory Out-of-Hospital Cardiac Arrest) has not found a relevant improvement of short-term mortality with extracorporeal cardiopulmonary resuscitation. In addition, the results of the recently published ECLS-SHOCK trial (Extracorporeal Life Support in Cardiogenic Shock) and ECMO-CS trial (Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock) discourage the routine use of VA-ECMO in patients with infarct-related cardiogenic shock. Ongoing clinical trials (ANCHOR [Assessment of ECMO in Acute Myocardial Infarction Cardiogenic Shock, NCT04184635], REVERSE [Impella CP With VA ECMO for Cardiogenic Shock, NCT03431467], UNLOAD ECMO [Left Ventricular Unloading to Improve Outcome in Cardiogenic Shock Patients on VA-ECMO, NCT05577195], PIONEER [Hemodynamic Support With ECMO and IABP in Elective Complex High-risk PCI, NCT04045873]) may clarify the usefulness of VA-ECMO in specific patient subpopulations and the efficacy of combined mechanical circulatory support strategies. Pending further data to refine patient selection and management recommendations for VA-ECMO, it remains uncertain whether the present usage of this device improves outcomes., Competing Interests: Disclosures None.

Background: Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster., Methods: Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3., Results: Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3., Conclusions: During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis., (© 2024. The Author(s).)

After anterior cruciate ligament reconstruction (ACLR), return to sprint is poorly documented in the literature. In soccer, return to sprint is an essential component of return to play and performance after ACLR. The characteristics of running in soccer are specific (velocity differences, nonlinear, intensity). It is important to address these particularities, such as curvilinear running, acceleration, deceleration, changes of direction, and variations in velocity, in the patient's rehabilitation program. Force, velocity, and acceleration capacities are key elements to sprint performance. Velocity-based training (VBT) has gained much interest in recent years and may have a role to play in optimizing return to play and return to sprint after ACLR. Force, velocity, and acceleration can be assessed using force-velocity-power and acceleration-speed profiles, which should inform rehabilitation. The purpose of this commentary is to describe a velocity-based return to sprint program which can be used during ACLR rehabilitation., Competing Interests: The authors declare no conflict of interest, (© The Author(s).)

Rationale: Severe cases of acute respiratory distress syndrome (ARDS) may require prolonged (>28 d) extracorporeal membrane oxygenation (ECMO). In nonresolving disease, recovery is uncertain, and lung transplant may be proposed. Objectives: This study aims to identify the variables influencing survival and to describe the functional status of these patients at 6 months. Methods: This was a retrospective, multicenter, observational cohort study including patients requiring ECMO support for coronavirus disease (COVID-19)-related ARDS for >28 days. Multivariate analysis was performed using Cox regression in preselected variables and in least absolute shrinkage and selection operator selected variables. In a post hoc analysis to account for confounders and differences in awake strategy use by centers, treatment effects of the awake strategy were estimated using an augmented inverse probability weighting estimator with robust standard errors clustered by center. Results: Between March 15, 2020 and March 15, 2021, 120 patients required ECMO for >28 days. Sixty-four patients (53.3%) survived decannulation, 62 (51.7%) were alive at hospital discharge, and 61 (50.8%) were alive at 6-month follow-up. In the multivariate analysis, age (1.09; 95% confidence interval [CI], 1.03-1.15; P  = 0.002) and an awake ECMO strategy (defined as the patient being awake, cooperative, and performing rehabilitation and physiotherapy with or without invasive mechanical ventilation at any time during the extracorporeal support) (0.14; 95% CI, 0.03-0.47; P  = 0.003) were found to be predictors of hospital survival. At 6 months, 51 (42.5%) patients were at home, 42 (84.3%) of them without oxygen therapy. A cutoff point of 47 ECMO days had a 100% (95% CI, 76.8-100%) sensitivity and 60% (95% CI, 44.3-73.6%) specificity for oxygen therapy at 6 months, with 100% specificity being found in 97 days. Conclusions: Patients with COVID-19 who require ECMO for >28 days can survive with nonlimiting lung impairment. Age and an awake ECMO strategy may be associated with survival. Longer duration of support correlates with need for oxygen therapy at 6 months.

Background: Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis., Objectives: The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX., Methods: Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class., Results: We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002)., Conclusions: The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy., Competing Interests: Conflicts of interest J.M.C. has participated as a speaker and/or advisor and/or principal investigator/senior investigator in clinical trials sponsored by for Celgene, Janssen, Lilly, Leo Pharma, Novartis, Pfizer, MSD, Biogen, Mylan, Amgen, AbbVie and Sandoz. A.G.-Q. acted as consultant and/or speaker for and/or participated in clinical trials as principal investigator and subinvestiator for AbbVie, Almirall, Amgen, Boehringer, Janssen, Leo Pharma, Lilly, Novartis, MSD, Pfizer-Wyeth and UCB. R.R.-D. acted as consultant and/or speaker for and/or participated in clinical trials as principal investigator for AbbVie, Almirall, Amgen, Boehringer, Janssen, Leo Pharma, Lilly, Novartis, MSD, Pfizer-Wyeth and UCB. A.S.-T. has served as a consultant and/or paid speaker for and/or participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Celgene, Janssen-Cilag, LEO Pharma, Lilly, Novartis and Pfizer. M.L.-V. acted as a consultant and speaker and participated in clinical trials for Janssen-Cilag, AbbVie, Boehringer, Celgene, Pfizer, Novartis, Lilly, Almirall, UCB, Kyowa Kirin and Leo Pharma. E.H.-A. has served as consultant and/or speaker with Leo Pharma, Novartis, Janssen, Lilly, Celgene and AbbVie. P.d.l.C. acted as a consultant and/or speaker for Janssen-Cilag, AbbVie, MSD, Pfizer, Novartis, Lilly, Almirall, UCB, Biogen, Celgene, Amgen, Sandoz, Sanofi and Leo Pharma. O.B.-R. acted as a consultant and/or speaker for Janssen-Cilag, AbbVie, Pfizer, Novartis, Lilly, Celgene, Leo Pharma, Amgen, Boehringer, UCB and Almirall. L.L.-E. participated as advisory board member and received educational grants from Janssen, AbbVie, MSD, Lilly, Novartis, LeoPharma and Pfizer. I.B. acted as a consultant and/or speaker for and/or participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including Janssen Pharmaceuticals Inc., Almirall SA, Lilly, AbbVie, Novartis, Celgene, Biogen Amgen, Leo Pharma, UCB, Pfizer-Wyeth and MSD. M.F. has participated as speaker and/or advisor for Janssen, Lilly, Novartis, Pfizer, MSD, AbbVie Celgene and Almirall. A.M. acted as consultant and/or speaker for AbbVie, Almirall, Celgene, Janssen, Leo Pharma, Lilly, Novartis. L.R. acted as a consultant and speaker for Janssen-Cilag, AbbVie, MSD, Pfizer, Novartis, Lilly, Almirall, Celgene and Leo Pharma. J.R.-M. acted as a consultant and/or speaker for and/or participated in clinical trials sponsored by AbbVie, Almirall, Janssen, Leo Pharma, Novartis, UCB, Pfizer, Lilly, Amgen and Boehringer Ingelheim. G.C. has been reimbursed by Janssen, AbbVie, Novartis, Pfizer, MSD and Celgene for advisory service and conference attendance. C.G.-D. participated as advisory board member for AbbVie, Almirall and speaker for Janssen, Lilly and Celgene. C.P.-M. acted as a consultant and/or speaker for Janssen-Cilag, AbbVie, MSD, Pfizer, Novartis, Lilly, Almirall, UCB, Celgene and Leo Pharma. E.D.A. has participated as a speaker and/or and/or PI/SI clinical trials sponsored by Amgen, Almirall, Janssen, Lilly, Leo Pharma, Novartis, UCB and AbbVie. J.A.S.-P. has served as consultant and/or speaker with Leo Pharma, Novartis, Janssen, Lilly, Celgene, AbbVie, Amgen, Sanofi, Almirall and Pfizer. D.P.R.-G. has been reimbursed by Pfizer, Janssen, Celgene, AbbVie, Novartis and LeoPharma for advisory services and conference attendance. I.G.D. received travel grants for congresses from AbbVie, MSD, Pfizer and Sanofi., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Streptococcal toxic shock syndrome (STTS) is a critical medical emergency marked by high morbidity and mortality, necessitating swift awareness, targeted treatment, and early source control due to its rapid symptom manifestation. This report focuses on a cohort of 13 patients admitted to Vall d'Hebron University Hospital Intensive Care Unit, Barcelona, from November 2022 to March 2023, exhibiting invasive Streptococcus pyogenes infections and meeting institutional sepsis code activation criteria. The primary infections were community-acquired pneumonia (61.5%) and skin/soft tissue infection (30.8%). All patients received prompt antibiotic treatment, with clinical source control through thoracic drainage (30.8%) or surgical means (23.1%). Organ support involved invasive mechanical ventilation, vasopressors, and continuous renal replacement therapy as per guidelines. Of note, 76.9% of patients experienced septic cardiomyopathy, and 53.8% required extracorporeal membrane oxygenation (ECMO). The study identified three distinct phenotypic profiles-hyperinflammatory, low perfusion, and hypogammaglobulinemic-which could guide personalized therapeutic approaches. STTS, with a mean SOFA score of 17 (5.7) and a 53.8% requiring ECMO, underscores the need for precision medicine-based rescue therapies and sepsis phenotype identification. Integrating these strategies with prompt antibiotics and efficient source control offers a potential avenue to mitigate organ failure, enhancing patient survival and recovery in the face of this severe clinical condition.

Rationale: Definitive guidelines for anticoagulation management during veno-venous extracorporeal membrane oxygenation (VV ECMO) are lacking, whereas bleeding complications continue to pose major challenges. Objectives: To describe anticoagulation modalities and bleeding events in adults receiving VV ECMO. Methods: This was an international prospective observational study in 41 centers, from December 2018 to February 2021. Anticoagulation was recorded daily in terms of type, dosage, and monitoring strategy. Bleeding events were reported according to site, severity, and impact on mortality. Measurements and Main Results: The study cohort included 652 patients, and 8,471 days on ECMO were analyzed. Unfractionated heparin was the initial anticoagulant in 77% of patients, and the most frequently used anticoagulant during the ECMO course (6,221 d; 73%). Activated partial thromboplastin time (aPTT) was the most common test for monitoring coagulation (86% of days): the median value was 52 seconds (interquartile range, 39 to 61 s) but dropped by 5.3 seconds after the first bleeding event (95% confidence interval, -7.4 to -3.2; P  < 0.01). Bleeding occurred on 1,202 days (16.5%). Overall, 342 patients (52.5%) experienced at least one bleeding event (one episode every 215 h on ECMO), of which 10 (1.6%) were fatal. In a multiple penalized Cox proportional hazard model, higher aPTT was a potentially modifiable risk factor for the first episode of bleeding (for 20-s increase; hazard ratio, 1.07). Conclusions: Anticoagulation during VV ECMO was a dynamic process, with frequent stopping in cases of bleeding and restart according to the clinical picture. Future studies might explore lower aPTT targets to reduce the risk of bleeding.

Purpose: This trial evaluates the addition of the PD-L1 antibody atezolizumab (ATZ) to standard-of-care fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) as a perioperative treatment for patients with resectable esophagogastric adenocarcinoma (EGA)., Methods: DANTE started as multicenter, randomized phase II trial, which was subsequently converted to a phase III trial. Here, we present the results of the phase II proportion, focusing on surgical pathology and safety outcomes on an exploratory basis. Patients with resectable EGA (≥cT2 or cN+) were assigned to either four preoperative and postoperative cycles of FLOT combined with ATZ, followed by eight cycles of ATZ maintenance (arm A) or FLOT alone (arm B)., Results: Two hundred ninety-five patients were randomly assigned (A, 146; B, 149) with balanced baseline characteristics between arms. Twenty-three patients (8%) had tumors with microsatellite instability (MSI), and 58% patients had tumors with a PD-L1 combined positive score (CPS) of ≥1. Surgical morbidity (A, 45%; B, 42%) and 60-day mortality (A, 3%; B, 2%) were comparable between arms. Downstaging favored arm A versus arm B (ypT0, 23% v 15% [one-sided P = .044]; ypT0-T2, 61% v 48% [one-sided P = .015]; ypN0, 68% v 54% [one-sided P = .012]). Histopathologic complete regression rates (pathologic complete response or TRG1a) were higher after FLOT plus ATZ (A, 24%; B, 15%; one-sided P = .032), and the difference was more pronounced in the PD-L1 CPS ≥10 (A, 33%; B, 12%) and MSI (A, 63%; B, 27%) subpopulations. Complete margin-free (R0) resection rates were relatively high in both arms (A, 96%; B, 95%). The incidence and severity of adverse events were similar in both groups., Conclusion: Within the limitations of the exploratory nature of the data, the addition of ATZ to perioperative FLOT is safe and improved postoperative stage and histopathologic regression.

We present the case of a man in his 70s admitted to the intensive care unit (ICU) after mitral valve replacement and coronary artery bypass graft surgery requiring extracorporeal membrane oxygenation support due to haemodynamic instability. He received anticoagulation therapy with heparin sodium and, after 5 days, the patient presented with thrombocytopenia and deep venous thrombosis. Heparin-induced thrombocytopenia was suspected based on a positive 4T score and confirmed by antiplatelet factor 4/heparin antibodies, so argatroban was initiated as an alternative anticoagulation therapy. In the following days the patient developed severe neutropenia requiring discontinuation of argatroban and the administration of granulocyte colony-stimulating factor. According to the Naranjo Adverse Drug Reaction Probability Scale, this event would be classified as a 'probable' argatroban-related adverse event. Argatroban should be conisdered as a possible cause of neutropenia and appropriate interventions need to be implemented due to the gravity of this adverse event in the ICU., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The Extracorporeal Life Support Organization (ELSO) registry captures clinical data and outcomes on patients receiving extracorporeal membrane oxygenation (ECMO) support across the globe at participating centers. It provides a very unique opportunity to benchmark outcomes and analyze the clinical course to help identify ways of improving patient outcomes. In this review, we summarize select adult ECMO articles published using the ELSO registry over the past 5 years. These articles highlight innovative utilization of the registry data in generating hypotheses for future clinical trials. Members of the ELSO Scientific Oversight Committee can be found here: https://www.elso.org/registry/socmembers.aspx ., Competing Interests: Disclosure: P.S. received personal fees from Fresenius and Getinge and a scientific grant from the European Society of Intensive Care Medicine and the European Commission (Horizon 2020 Fast Track to Innovation: NCT04115709). K.S. acknowledges research support from Metro North Hospital and Health Service. A.A. receives research support from Francis Family Foundation and NIGMS P20 GM 103652 grant. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Extracorporeal Membrane Oxygenation (ECMO) is commonly associated with a high blood transfusion requirement. Jehovah's Witness patients present a particular challenge. The impossibility of transfusing blood cells and starting anticoagulation treatment are common contraindications for this supportive measure. Here we report the case of a Jehovah's Witness patient with refractory hypoxemia due to influenza A H1N1 pneumonia who required venovenous ECMO for 11 days. We describe the use of a bloodless approach to reduce the waste of blood, avoiding anticoagulation, and improving red blood cell production. We then summarize the current literature on the use of ECMO in Jehovah's Witness patients and, finally, we propose some recommendations for their management., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Purpose: Extracorporeal membrane oxygenation (ECMO) continues to play an essential role in organ support in cardiogenic shock or acute respiratory distress syndrome and bridging to transplantation. The main purpose of the present survey was to define which clinical and organizational practices are adopted for the administration of physiotherapy in adult patients undergoing ECMO support worldwide., Methods: This international survey was conceived in November 2021. The survey launch was announced at the 10th EuroELSO (European ELSO chapter) Congress, London, May 2022., Results: The survey returned 32 questionnaires from 29 centers across 14 countries. 17 centers (53.1%) had more than 30 intensive care unit beds available and most (46.8%) were able to care for five to 10 patients on extracorporeal life support simultaneously. The predominant physiotherapist-to-patient ratio was 1:>5 (37.5%); physiotherapy was available 5/7 days and 7/7 days by 31.2% and 25% respectively. Respiratory physiotherapy was not defined by a specific protocol in most centers (46.8%) while 31.2% declared that the treatment commences less than 12 h after sedation is stopped/reduced. Mostly, early physiotherapy in non-cooperative ventilated patients was provided within the first 48 h (68.6%) and consisted of as passive range of motion, in-bed positioning, and splinting. Postural passages and sitting were provided to patients and walking was included in those advanced motor activities which are part of the treatment., Conclusion: Physiotherapy in patients on ECLS is feasible, however substantial variability exists between centers with a trend of delivering not protocolized and understaffed rehabilitation practices., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.