Search

Introduction: Although largely used, the place of oxygen therapy and its devices in patients with acute hypoxemic respiratory failure (ARF) deserves to be clarified. The French Intensive Care Society (Société de Réanimation de Langue Française, SRLF) and the French Emergency Medicine Society (Société Française de Médecine d'Urgence, SFMU) organized a consensus conference on oxygen therapy in ARF (excluding acute cardiogenic pulmonary oedema and hypercapnic exacerbation of chronic obstructive diseases) in December 2023. Methods: A committee without any conflict of interest (CoI) with the subject defined 7 generic questions and drew up a list of sub questions according to the population, intervention, comparison and outcomes (PICO) model. An independent work group reviewed the literature using predefined keywords. The quality of the data was assessed using the GRADE methodology. Fifteen experts in the field from both societies proposed their own answers in a public session and answered questions from the jury (a panel of 16 critical-care and emergency medicine physicians, nurses and physiotherapists without any CoI) and the public. The jury then met alone for 48 h to write its recommendations. Results: The jury provided 22 statements answering 11 questions: in patients with ARF (1) What are the criteria for initiating oxygen therapy? (2) What are the targets of oxygen saturation? (3) What is the role of blood gas analysis? (4) When should an arterial catheter be inserted? (5) Should standard oxygen therapy, high-flow nasal cannula oxygen therapy (HFNC) or continuous positive airway pressure (CPAP) be preferred? (6) What are the indications for non-invasive ventilation (NIV)? (7) What are the indications for invasive mechanical ventilation? (8) Should awake prone position be used? (9) What is the role of physiotherapy? (10) Which criteria necessarily lead to ICU admission? (11) Which oxygenation device should be preferred for patients for whom a do-not-intubate decision has been made? Conclusion: These recommendations should optimize the use of oxygen during ARF. [ABSTRACT FROM AUTHOR]

Medical management is the standard treatment of chronic type B aortic dissection (CTBAD). However, the roles of open surgical repair (OSR) and thoracic endovascular repair (TEVAR) in patients with CTBAD remain controversial. Thus, this study aimed to assess and compare the mid- and long-term clinical outcomes of OSR via left thoracotomy with that of TEVAR for CTBAD. The data of 85 consecutive patients who underwent surgery for CTBAD from April 2007 to May 2021 were retrospectively reviewed. The patients were divided into two groups: Group G, which included patients who underwent OSR, and Group E, which included patients who underwent TEVAR. Groups G and E comprised 33 and 52 patients, respectively. Preoperative and postoperative computed tomography (CT) studies were retrospectively analyzed for the maximum diameter. The mean duration of the follow-up period was 5.8 years. Operative mortality did not occur. There was no difference in complications, such as stroke (G: 2 vs. E: 0, p = 0.30), paraplegia (G: 1 vs. E: 1, p = 0.66), and respiratory failure (G: 2, vs. E: 0, p = 0.30). The difference in preoperative factors was observed, including the intervals between onset and operation (G; 4.9 years vs. E; 1.9 years, p < 0.01), maximum diameter in preoperative CT (G; 59.0 mm vs. E; 50.5 mm, p < 0.001), and maximum false lumen diameter (G; 35.5 mm vs. E; 29.0 mm, p < 0.01). There was no significant difference in the mid- and long-term survival rates (p = 0.49), aorta-related deaths (p = 0.33), and thoracic re-intervention rates (p = 0.34). Postoperative adverse events occurred in Group E: four cases of retrospective type A aortic dissection, two cases of aorto-bronchial fistula, and one case of aorto-esophagus fistula. Aorta-related death and re-intervention rates crossed over in both groups after seven years postoperatively. Although endovascular repair of CTBAD is less invasive, the rate of freedom from re-intervention was unsatisfactory. Some fatal complications were observed in the endovascular group, and the mid- and long-term outcomes were reversed compared with those in the OSR group. Although OSR is an invasive procedure, it could be performed safely without perioperative complications. OSR has more feasible mid- and long-term outcomes. [ABSTRACT FROM AUTHOR]

The prone position is an immediately available and easily implemented procedure that was introduced more than 50 years ago as a method for improvement of gas exchange in patients with acute respiratory distress syndrome (ARDS). In the meantime, a survival advantage could also be shown in patients with severe ARDS, which led to the recommendation of the prone position for treatment of severe ARDS by expert consensus and specialist society guidelines. The continuing coronavirus disease 2019 (COVID-19) pandemic moved the prone position to the forefront of medicine, including the widespread implementation of the prone position for awake, spontaneously breathing nonintubated patients with acute hypoxemic respiratory insufficiency. The survival advantage is possible due to a reduction of the ventilator-associated lung damage. In this article, the physiological effects, data on clinical results, practical considerations and open questions with respect to the prone position are discussed. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is the end stage of lung injury and chronic lung diseases that results in diminished lung function, respiratory failure, and ultimately mortality. Despite extensive research, the pathogenesis of this disease remains elusive, and effective therapeutic options are currently limited, posing a significant clinical challenge. In addition, research on traditional Chinese medicine and naturopathic medicine is hampered by several complications due to complex composition and lack of reference compounds. Natural product monomers, possessing diverse biological activities and excellent safety profiles, have emerged as potential candidates for preventing and treating PF. The effective anti-PF ingredients identified can be generally divided into flavonoids, saponins, polysaccharides, and alkaloids. Specifically, these monomeric compounds can attenuate inflammatory response, oxidative stress, and other physiopathological processes of the lung through many signaling pathways. They also improve pulmonary factors. Additionally, they ameliorate epithelial–mesenchymal transition (EMT) and fibroblast–myofibroblast transdifferentiation (FMT) by regulating multiple signal amplifiers in the lungs, thereby mitigating PF. This review highlights the significant role of monomer compounds derived from natural products in reducing inflammation, oxidative stress, and inhibiting EMT process. The article provides comprehensive information and serves as a solid foundation for further exploration of new strategies to harness the potential of botanicals in the treatment of PF. [ABSTRACT FROM AUTHOR]

Background: Chronic respiratory insufficiency from progressive muscle weakness causes morbidity and mortality in late-onset Pompe disease (LOPD). Previous Pompe Registry (NCT00231400) analyses for ≤ 5 years' alglucosidase alfa treatment showed a single linear time trend of stable forced vital capacity (FVC) % predicted. Methods: To assess longer term Pompe Registry data, piecewise linear mixed model regression analyses estimated FVC% predicted trajectories in invasive-ventilator-free patients with LOPD aged ≥ 5 years. We estimated annual FVC change 0–6 months, > 6 months–5 years, and > 5–13 years from treatment initiation, adjusting for baseline age, sex, and non-invasive ventilation. Findings: Among 485 patients (4612 FVC measurements; 8.3 years median follow-up), median ages at symptom onset, diagnosis, and alglucosidase alfa initiation were 34.3, 41.1, and 44.9 years, respectively. FVC% increased during the first 6 months' treatment (slope 1.83%/year; 95% confidence interval: 0.66, 3.01; P = 0.0023), then modestly declined −0.54%/year (−0.79, −0.30; P < 0.0001) during > 6 months–5 years, and −1.00%/year (−1.36, −0.63; P < 0.0001) during > 5–13 years. The latter two periods' slopes were not significantly different from each other (Pdifference = 0.0654) and were less steep than published natural history slopes (−1% to −4.6%/year). Estimated individual slopes were ≥ 0%/year in 96.1%, 30.3%, and 13.2% of patients during the 0–6 month, > 6 month–5 year, and > 5–13 year periods, respectively. Conclusion: These real-world data indicate an alglucosidase alfa benefit on FVC trajectory that persists at least 13 years compared with published natural history data. Nevertheless, unmet need remains since most individuals demonstrate lung function decline 5 years after initiating treatment. Whether altered FVC trajectory impacts respiratory failure incidence remains undetermined. Trial registration: This study was registered (NCT00231400) on ClinicalTrials.gov on September 30, 2005, retrospectively registered. [ABSTRACT FROM AUTHOR]

Purpose: Although noninvasive ventilation (NIV) may reduce reintubation in patients with acute hypoxemic respiratory failure following abdominal surgery, this strategy has not been specifically assessed in patients with obesity. Methods: We conducted a post hoc analysis of a multicenter randomized controlled trial comparing NIV delivered via facial mask to standard oxygen therapy among patients with obesity and acute hypoxemic respiratory failure within 7 days after abdominal surgery. The primary outcome was reintubation within 7 days. Secondary outcomes were invasive ventilation-free days at day 30, intensive care unit (ICU)-acquired pneumonia and 30-day survival. Results: Among 293 patients with hypoxemic respiratory failure following abdominal surgery, 76 (26%) patients had obesity and were included in the intention-to-treat analysis. Reintubation rate was significantly lower with NIV (13/42, 31%) than with standard oxygen therapy (19/34, 56%) within 7 days (absolute difference: − 25%, 95% confidence interval (CI) − 49 to − 1%, p = 0.03). NIV was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (27.1 ± 8.6 vs 22.7 ± 11.1 days; p = 0.02), while fewer patients developed ICU-acquired pneumonia (1/42, 2% vs 6/34, 18%; p = 0.04). The 30-day survival was 98% in the NIV group (41/42) versus 85% in the standard oxygen therapy (p = 0.08). In patients with body mass index (BMI) < 30 kg/m2, no significant difference was observed between NIV (36/105, 34%) and standard oxygen therapy (47/109, 43%, p = 0.03). An interaction test showed no statistically significant difference between the two subsets (BMI ≥ 30 kg/m2 and BMI < 30 kg/m2). Conclusions: Among patients with obesity and hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of reintubation within 7 days, contrary to patients without obesity. However, no interaction was found according to the presence of obesity or not, suggesting either a lack of power to conclude in the non-obese subgroup despite existing differences, or that the statistical difference found in the overall sample was driven by a large effect in the obese subsets. [ABSTRACT FROM AUTHOR]

Purpose: Optimal oxygenation targets for patients with acute hypoxemic respiratory failure in the intensive care unit (ICU) are not clearly defined due to substantial variability in design of previous trials. This study aimed to perform a pre-specified individual patient data meta-analysis of the Handling Oxygenation Targets in the ICU (HOT-ICU) and the Handling Oxygenation Targets in coronavirus disease 2019 (COVID-19) (HOT-COVID) trials to compare targeting a partial pressure of arterial oxygen (PaO2) of 8–12 kPa in adult ICU patients, assessing both benefits and harms. Methods: We assessed 90-day all-cause mortality and days alive without life support in 90 days using a generalised mixed model. Heterogeneity of treatment effects (HTE) was evaluated in 14 subgroups, and results graded using the Instrument to assess the Credibility of Effect Modification Analyses (ICEMAN). Results: At 90 days, mortality was 40.4% (724/1792) in the 8 kPa group and 40.9% (733/1793) in the 12 kPa group (risk ratio, 0.99; 95% confidence interval [CI] 0.92–1.07; P = 0.80). No difference was observed in number of days alive without life support. Subgroup analyses indicated more days alive without life support in COVID-19 patients targeting 8 kPa (P = 0.04) (moderate credibility), and lower mortality (P = 0.03) and more days alive without life support (P = 0.02) in cancer-patients targeting 12 kPa (low credibility). Conclusion: This study reported no overall differences comparing a PaO2 target of 8–12 kPa on mortality or days alive without life support in 90 days. Subgroup analyses suggested HTE in patients with COVID-19 (moderate credibility) and cancer (low credibility). [ABSTRACT FROM AUTHOR]

Etizolam is a thienodiazepine derivative which produces an anxiolytic effect similar to benzodiazepines such as alprazolam (Xanax). Like classic benzodiazepines, etizolam has a high affinity towards the GABAA receptor, and allosterically potentiates the effects of GABA resulting in neuronal hyperpolarization related to chloride influx. When taken in therapeutic doses, etizolam produces a similar effect to Xanax. Counterfeit Xanax tablets contain variable amounts of etizolam. Tablets with high amounts of etizolam can cause toxicity if ingested, especially when combined with other substances. When toxic symptoms occur in patients, they may include severe sedation, unconsciousness, and depression of the medullary respiratory center. In this regard, there is the potential for death. Additionally, the rise in fake Xanax tablets containing etizolam and other counterfeit medications has been exacerbated by the difference in regulations regarding these substances in different countries as well as the illegal drug trade. Healthcare providers may also play a role through the over- or underprescribing of certain medications. Thus, in order to combat the rise in counterfeit medications such as fake Xanax, international cooperation, regulation, and enforcement of laws pertaining to the manufacture, prescription, and distribution of these substances are needed. [ABSTRACT FROM AUTHOR]

Background: The accuracy of a diagnostic test depends on its intrinsic characteristics and the disease incidence. This study aims to depict post-test probability of Pneumocystis pneumonia (PJP), according to results of PCR and Beta-D-Glucan (BDG) tests in patients with acute respiratory failure (ARF). Materials and methods: Diagnostic performance of PCR and BDG was extracted from literature. Incidence of Pneumocystis pneumonia was assessed in a dataset of 2243 non-HIV immunocompromised patients with ARF. Incidence of Pneumocystis pneumonia was simulated assuming a normal distribution in 5000 random incidence samples. Post-test probability was assessed using Bayes theorem. Results: Incidence of PJP in non-HIV ARF patients was 4.1% (95%CI 3.3-5). Supervised classification identified 4 subgroups of interest with incidence ranging from 2.0% (No ground glass opacities; 95%CI 1.4–2.8) to 20.2% (hematopoietic cell transplantation, ground glass opacities and no PJP prophylaxis; 95%CI 14.1–27.7). In the overall population, positive post-test probability was 32.9% (95%CI 31.1–34.8) and 22.8% (95%CI 21.5–24.3) for PCR and BDG, respectively. Negative post-test probability of being infected was 0.10% (95%CI 0.09–0.11) and 0.23% (95%CI 0.21–0.25) for PCR and BDG, respectively. In the highest risk subgroup, positive predictive value was 74.5% (95%CI 72.0-76.7) and 63.8% (95%CI 60.8–65.8) for PCR and BDG, respectively. Conclusion: Although both tests yield a high intrinsic performance, the low incidence of PJP in this cohort resulted in a low positive post-test probability. We propose a method to illustrate pre and post-test probability relationship that may improve clinician perception of diagnostic test performance according to disease incidence in predefined clinical settings. [ABSTRACT FROM AUTHOR]

Cell-free DNA (cfDNA) is released from injured cells and aggravates inflammation. Patients with coronavirus disease (COVID-19) often develop pneumonia and respiratory failure, and require oxygen therapy (OT), including mechanical ventilation (MV). It remains unclear whether cfDNA predicts the risk of receiving OT or MV in COVID-19 patients. Therefore, we hypothesized that circulating cfDNA levels could reflect the severity of respiratory failure and determine a therapeutic approach for oxygenation in patients with COVID-19. We analyzed cfDNA levels in serum samples from 95 hospitalized patients with COVID-19 at Showa University Hospital (Tokyo, Japan). cfDNA levels were assessed by measuring the copy numbers of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) using quantitative real-time PCR (qPCR). Both cf-nDNA and cf-mtDNA levels were negatively correlated with adjusted SpO2 for FiO2 (SpO2/FiO2 ratio). Elevated cf-nDNA and cf-mtDNA levels were associated with the requirement for OT or MV during patient admission. Multivariate logistic regression analysis revealed that cf-nDNA and cf-mtDNA levels were independent risk factors for OT and MV. These results suggest that both serum cf-nDNA and cf-mtDNA could serve as useful early biomarkers to indicate the necessity of OT or MV in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background: The recent global pandemic due to severe acute respiratory syndrome coronavirus-2 resulted in a high rate of multi-organ failure and mortality in a large patient population across the world. As such, a possible correlation between acute kidney injury (AKI) and increased mortality rate in these patients has been suggested in literature. Methods: This is a two-year retrospective study of critically ill adult patients infected with COVID-19 that were admitted to the intensive care unit (ICU) on ventilatory support. Two groups of patients were identified in this study, those who were directly admitted to the ICU or those who were initially admitted to the Medical Floor and were later transferred to the ICU due to either worsening respiratory status or change in their hemodynamic conditions. Within each group, three subgroups were created based on the status of AKI, namely, those who did not develop AKI, those who developed AKI, and those who with previous history of dialysis dependent AKI. Results: The AKI subgroup had the highest mortality rate in the ICU and Floor patients. Of note, those patients who were directly admitted to the Floor and were later transferred to the ICU for worsening conditions also experienced a higher mortality rate if they had developed AKI during their course of hospital stay. Conclusions: This study identified a statistically significant higher mortality in patients who developed AKI than those who did not develop AKI among critically ill patients. Trial registration: Clinicaltrials.gov registration number NCT05964088. Date of registration: July 24 2023. [ABSTRACT FROM AUTHOR]

COVID-19 disease is associated with a hyperinflammatory, pro-thrombotic state and a high mortality. Our primary objective was to assess the change in inflammatory and thrombotic markers associated with PEX, and secondary objectives were to assess the effects of PEX on progression of respiratory failure and incidence of acute thrombotic events. We conducted a prospective, phase II, non-blinded randomised control trial of plasma exchange compared to standard of care in critically ill adults with severe COVID-19 associated respiratory failure, requiring supplemental oxygen or ventilatory support and elevated thrombo-inflammatory markers (LDH, CRP, ferritin, and D-Dimer). Patients randomised to receive PEX were treated with a daily single volume plasma exchange for a minimum of five days. Twenty-two patients were randomised of who 11 received PEX. Demographic and clinical characteristics were similar between groups at presentation. PEX was associated with a significant reduction in pro-thrombotic markers FVIII, VWF and VWF Ag: ADAMTS 13 ratio (p < 0.001). There were no differences in the reduction of inflammatory markers, severity of respiratory failure (p = 0.7), thrombotic events (p = 0.67), or mortality (p > 0.99) at 28 days. PEX successfully reduced pro-thrombotic markers, although was not associated with reduction in inflammatory markers, respiratory failure, or thrombotic events. Trial registration: (NCT04623255); first posted on 10/11/2020. [ABSTRACT FROM AUTHOR]

Context: Critically ill patients, especially those with respiratory failure associated with multiple comorbidities, are at risk of recurrent ICU admission and consuming a significant portion of medical resources. Aim: To study the risk factors and common etiologies of readmission among surviving patients with acute respiratory failure in Mansoura University's respiratory intensive care unit during the year 2023. Settings and design: This was a retrospective cohort study. Patients and methods: This study included all patients with acute respiratory failure who were admitted to Mansoura University's respiratory intensive care unit (RICU), from January 2023 to December 2023. Deceased patients after initial admission or those with incomplete data were not included in the study. All data related to patient's demographics, type of respiratory failure, type of respiratory support, associated comorbidities, length of ICU stay, and causes of readmission were collected from the registration system database. Results: Eight-hundred-thirty (830) cases that were admitted to the Mansoura University's RICU with respiratory failure in the year 2023 were enrolled in the study, and 84 cases (10.1%) of them were readmitted. COPD exacerbation was the most common cause of readmission (35.7%) followed by pneumonia (21.4%) and OSA exacerbation (20.2%). Results showed that the significant independent predictors of readmission were being male [AOR (95% CI): 1.8 (1.01–3.1), p: 0.046], having organ failure (renal/liver) [AOR (95% CI): 29.9 (7.9–113.4), p ≤ 0.001], and length of ICU stay more than 12 days [AOR (95% CI): 4.8 (2.6–8.6), p ≤ 0.001]. Also, the type of respiratory failure and the type of respiratory support received were significantly associated with readmission in the univariate analysis; however, they were insignificant in the multivariate analysis. Conclusion: The rate of readmission was not high (only 10.3%). The most common causes of readmission were COPD exacerbation, followed by pneumonia and OSA exacerbation, respectively. Type of respiratory failure, male gender, the presence of other organ failure, and length of ICU stay are significant independent predictors of readmission in Mansoura University's RICU during the year 2023. Therefore, higher-risk individuals should receive attention and careful assessment before discharge from the ICU to reduce the rate of readmission. Trial registration: ClinicalTrials.gov identifier: NCT06291636. [ABSTRACT FROM AUTHOR]

Copyright of Innere Medizin (2731-7080) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Interstitial lung abnormalities (ILAs) are immune checkpoint inhibitor (ICI)-related pneumonitis (ICI-P) risk factors. However, the relationship between imaging patterns and immunotherapy outcomes, and treatment strategies remain unclear in patients with non-small cell lung cancer (NSCLC) and ILAs. We retrospectively evaluated patients with ILAs-complicated NSCLC who received ICI therapy. ILAs were subcategorized as non-subpleural, subpleural non-fibrotic, and subpleural fibrotic (SF) based on the 2020 position paper by the Fleischner Society. We investigated ICI-P incidence, ICI-P risk factors, lung cancer prognosis, and ILAs radiological progression. Of the 481 ICI-treated patients, 79 (16.4%) had ILAs (45 non-SF and 34 SF). The ICI-P cumulative incidence (hazard ratio, 4.57; 95% confidence interval [CI], 1.90–10.98; p = 0.001) and any grade and grade ≥ 3 ICI-P incidences were higher in patients with SF-ILAs than in those with non-SF-ILAs (all grades: 7/45 [15.6%)] vs. 18/34 [52.9%]; p < 0.001; grade ≥ 3: 1/45 [2.2%] vs. 10/34 [29.4%]; p = 0.001). According to multivariate analysis, SF-ILAs independently predicted ICI-P (odds ratio, 5.35; 95% CI 1.62–17.61; p = 0.006). Patients with SF-ILAs had shorter progression-free and overall survival and higher ICI-P-related respiratory failure death rates than those with non-SF-ILAs. Approximately 2.5 times more patients with SF-ILAs showed progression by the 2-year follow-up than those with non-SF-ILAs. SF-ILAs is an independent strong predictor of ICI-P development in patients with NSCLC, may increase ICI-P severity, worsen prognosis, and accelerate ILAs progression. ILAs subcategorization is an important treatment strategy for patients with lung cancer treated with ICIs. [ABSTRACT FROM AUTHOR]

Background: Cerebral microbleeds (CMBs) have been described in critically ill patients with respiratory failure, acute respiratory distress syndrome (ARDS), or sepsis. This scoping review aimed to systematically summarize existing literature on critical illness–associated CMBs. Methods: Studies reporting on adults admitted to the intensive care unit for respiratory failure, ARDS, or sepsis with evidence of CMBs on magnetic resonance imaging were included for review following a systematic search across five databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science) and a two-stage screening process. Studies were excluded if patients' CMBs were clearly explained by another process of neurological injury. Results: Forty-eight studies reporting on 216 critically ill patients (mean age 57.9, 18.4% female) with CMBs were included. Of 216, 197 (91.2%) patients developed respiratory failure or ARDS, five (2.3%) patients developed sepsis, and 14 (6.5%) patients developed both respiratory failure and sepsis. Of 211 patients with respiratory failure, 160 (75.8%) patients had coronavirus disease 2019. The prevalence of CMBs among critically ill patients with respiratory failure or ARDS was 30.0% (111 of 370 patients in cohort studies). The corpus callosum and juxtacortical area were the most frequently involved sites for CMBs (64.8% and 41.7% of all 216 patients, respectively). Functional outcomes were only reported in 48 patients, among whom 31 (64.6%) were independent at discharge, four (8.3%) were dependent at discharge, and 13 (27.1%) did not survive until discharge. Cognitive outcomes were only reported in 11 of 216 patients (5.1%), all of whom showed cognitive deficits (nine patients with executive dysfunction and two patients with memory deficits). Conclusions: Cerebral microbleeds are commonly reported in patients with critical illness due to respiratory failure, ARDS, or sepsis. CMBs had a predilection for the corpus callosum and juxtacortical area, which may be specific to critical illness–associated CMBs. Functional and cognitive outcomes of these lesions are largely unknown. [ABSTRACT FROM AUTHOR]

Background: Evidence for the management of pregnant women with acute hypoxaemic respiratory failure (AHRF) is currently lacking. The likelihood of avoiding intubation and the risks of continuing the pregnancy under invasive ventilation remain undetermined. We report the management and outcome of pregnant women with pneumonia related to SARS-CoV-2 admitted to the ICU of tertiary maternity hospitals of the Paris area. Methods: We studied a retrospective cohort of pregnant women admitted to 15 ICUs with AHRF related to SARS-CoV-2 defined by the need for O2 ≥ 6 L/min, high-flow nasal oxygen (HFNO), non-invasive or invasive ventilation. Trajectories were assessed to determine the need for intubation and the possibility of continuing the pregnancy on invasive ventilation. Results: One hundred and seven pregnant women, 34 (IQR: 30–38) years old, at a gestational age of 27 (IQR: 25–30) weeks were included. Obesity was present in 37/107. Intubation was required in 47/107 (44%). Intubation rate according to respiratory support was 14/19 (74%) for standard O2, 17/36 (47%) for non-invasive ventilation and 16/52 (31%) for HFNO. Factors significantly associated with intubation were pulmonary co-infection: adjusted OR: 3.38 (95% CI 1.31–9.21), HFNO: 0.11 (0.02–0.41) and non-invasive ventilation: 0.20 (0.04–0.80). Forty-six (43%) women were delivered during ICU stay, 39/46 (85%) for maternal pulmonary worsening, 41/46 (89%) at a preterm stage. Fourteen non-intubated women were delivered under regional anaesthesia; 9/14 ultimately required emergency intubation. Four different trajectories were identified: 19 women were delivered within 2 days after ICU admission while not intubated (12 required prolonged intubation), 23 women were delivered within 2 days after intubation, in 11 intubated women pregnancy was continued allowing delivery after ICU discharge in 8/11, 54 women were never intubated (53 were delivered after discharge). Timing of delivery after intubation was mainly dictated by gestational age. One maternal death and one foetal death were recorded. Conclusion: In pregnant women with AHRF related to SARS-CoV-2, HFNO and non-invasive mechanical ventilation were associated with a reduced rate of intubation, while pulmonary co-infection was associated with an increased rate. Pregnancy was continued on invasive mechanical ventilation in one-third of intubated women. Study registration retrospectively registered in ClinicalTrials (NCT05193526). [ABSTRACT FROM AUTHOR]

Most very premature infants breathe at birth but require respiratory support in order to stimulate and support their breathing. A significant proportion of premature infants are affected by chorioamnionitis, defined as an umbrella term for antenatal inflammation of the foetal membranes and umbilical vessels. Chorioamnionitis produces inflammatory mediators that potentially depress the respiratory drive generated in the brainstem. Such respiratory depression could maintain itself by delaying lung aeration, hampering respiratory support at birth and putting infants at risk of hypoxic injury. This inflammatory-mediated respiratory depression may contribute to an association between chorioamnionitis and increased requirement of neonatal resuscitation in premature infants at birth. This narrative review summarises mechanisms on how respiratory drive and spontaneous breathing could be influenced by chorioamnionitis and provides possible interventions to stimulate spontaneous breathing. Conclusion: Chorioamnionitis could possibly depress respiratory drive and spontaneous breathing in premature infants at birth. Interventions to stimulate spontaneous breathing could therefore be valuable. What is Known: • A large proportion of premature infants are affected by chorioamnionitis, antenatal inflammation of the foetal membranes and umbilical vessels. What is New: • Premature infants affected by chorioamnionitis might be exposed to higher concentrations of respiratory drive inhibitors which could depress breathing at birth. • Premature infants affected by chorioamnionitis seem to be associated with a higher and more extensive requirement of resuscitation at birth. [ABSTRACT FROM AUTHOR]

Recommendations for the treatment of myasthenia gravis (MG) have been difficult to develop because of limited evidence from large randomized controlled trials. New drugs and treatment approaches have recently been shown to be effective in phase 3 studies in seropositive generalized (g) MG. One such drug is efgartigimod, a human-Fc-fragment of IgG1, with a high affinity for the endosomal FcRn. We conducted a multicenter study to evaluate the real-world clinical and safety effects of efgartigimod in 22 gMG patients. We evaluated the strategies for the timing of re-treatment with it. The participants received a total of 59 efgartigimod -treatment cycles. The median number of cycles was 2 (range 1–6). Twenty patients (86.3%) improved by at least 2 MG-ADL points after the first treatment cycle. The median MG-ADL score at baseline was 6.5 (range: 3–17) and 2.5 (range: 0–9) post-treatment (p < 0.001). A consistent improvement of at least 2 points in the MG-ADL score after each cycle occurs in 18 patients. The effect duration of the treatment was usually between 4 and 12 weeks. Two major clinical patterns of treatment response were found. Treatment with efgartigimod was also associated with significant reductions of prednisone doses Overall, the treatment was safe and associated with only minor adverse events. The single fatality was apparently due tosevere respiratory failure. We found that efgartigimod is clinically effective, may be used as a steroid sparing agent and is generally safe for gMG patients. We recommend a personalized preventive treatment approach until clinical stabilization, followed by discontinuation and periodic evaluations. [ABSTRACT FROM AUTHOR]

Introduction: Long-term oxygen therapy (LTOT) is reported to improve survival in patients with chronic respiratory failure. We aimed to describe effectiveness, burden, and cost of illness of patients treated with portable oxygen concentrators (POC) compared to other LTOT options. Methods: This retrospective comparative analysis included adult patients with chronic respiratory insufficiency and failure (CRF) upon a first delivery of LTOT between 2014 and 2019 and followed until December 2020, based on the French national healthcare database SNDS. Patients using POC, alone or in combination, were compared with patients using stationary concentrators alone (aSC), or compressed tanks (CTC) or liquid oxygen (LO2), matched on the basis of age, gender, comorbidities, and stationary concentrator use. Results: Among 244,719 LTOT patients (mean age 75 ± 12, 48% women) included, 38% used aSC, 46% mobile oxygen in the form of LO2 (29%) and POC (18%), whereas 9% used CTC. The risk of death over the 72-month follow-up was estimated to be 13%, 15%, and 12% lower for patients in the POC group compared to aSC, CTC, and LO2, respectively. In the POC group yearly mean total costs per patient were 5% higher and 4% lower compared to aSC and CTC groups, respectively, and comparable in the LO2 group. The incremental cost-effectiveness ratio (ICER) of POC was €8895, €6288, and €13,152 per year of life gained compared to aSC, CTC, and LO2, respectively. Conclusion: Within the POC group, we detected an association between higher mobility (POCs autonomy higher than 5 h), improved survival, lower costs, and ICER − €6 238, compared to lower mobility POCs users. [ABSTRACT FROM AUTHOR]

We are entering the post-antibiotic era. Antimicrobial resistance (AMR) is a critical problem in chronic lung infections resulting in progressive respiratory failure and increased mortality. In the absence of emerging novel antibiotics to counter AMR infections, bacteriophages (phages), viruses that infect bacteria, have become a promising option for chronic respiratory infections. However, while personalized phage therapy is associated with improved outcomes in individual cases, clinical trials demonstrating treatment efficacy are lacking, limiting the therapeutic potential of this approach for respiratory infections. In this review, we address the current state of phage therapy for managing chronic respiratory diseases. We then discuss how phage therapy may address major microbiologic obstacles which hinder disease resolution of chronic lung infections with current antibiotic-based treatment practices. Finally, we highlight the challenges that must be addressed for successful phage therapy clinical trials. Through this discussion, we hope to expand on the potential of phages as an adjuvant therapy in chronic lung infections, as well as the microbiologic challenges that need to be addressed for phage therapy to expand beyond personalized salvage therapy. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) is often the last resort for escalation of treatment in patients with severe acute respiratory distress syndrome (ARDS). The success of treatment is mainly determined by patient-specific factors, such as age, comorbidities, duration and invasiveness of the pre-existing ventilation treatment as well as the expertise of the treating ECMO center. In particular, the adjustment of mechanical ventilation during ongoing ECMO treatment remains controversial. Although a reduction of invasiveness of mechanical ventilation seems to be reasonable due to physiological considerations, no improvement in outcome has been demonstrated so far for the use of ultraprotective ventilation regimens. [ABSTRACT FROM AUTHOR]

Background: Plasmapheresis is widely used for severe hypertriglyceridemia-associated acute pancreatitis (HTG-AP) to remove excessive triglycerides from plasma. This study aimed to evaluate whether plasmapheresis could improve the duration of organ failure in HTG-AP patients. Methods: We analyzed a cohort of patients from a multicenter, prospective, long-running registry (the PERFORM) collecting HTG-AP patients admitted to the study sites within 72 h from the onset of symptoms. This study was based on data collected from November 2020 to March 2023. Patients who had organ failure at enrollment were involved in the analyses. The primary outcome was time to organ failure resolution within 14 days. Multivariable Cox regression model was used to evaluate the association between plasmapheresis and time to organ failure resolution. Directed acyclic graph (DAG) was used to identify potential confounders. Results: A total of 122 HTG-AP patients were included (median [IQR] sequential organ failure assessment (SOFA) score at enrollment, 3.00 [2.00–4.00]). Among the study patients, 46 underwent plasmapheresis, and 76 received medical treatment. The DAG revealed that baseline serum triglyceride, APACHE II score, respiratory failure, cardiovascular failure, and renal failure were potential confounders. After adjusting for the selected confounders, there was no significant difference in time to organ failure resolution between patients undergoing plasmapheresis and those receiving exclusive medical treatment (HR = 1.07; 95%CI 0.68–1.68; P = 0.777). Moreover, the use of plasmapheresis was associated with higher ICU requirements (97.8% [45/46] vs. 65.8% [50/76]; OR, 19.33; 95%CI 2.20 to 169.81; P = 0.008). Conclusions: In HTG-AP patients with early organ failure, plasmapheresis was not associated with accelerated organ failure resolution compared to medical treatment but may be associated with more ICU admissions. Trial registration: The PERFORM study was registered in the Chinese Clinical Trial Registry (ChiCTR2000039541). Registered 30 October 2020. [ABSTRACT FROM AUTHOR]

Vertebrobasilar artery dissecting aneurysms (VBDAs) are the most surgically challenging type of aneurysm. Cerebral revascularization is the ultimate treatment for complex VBDAs. We retrospectively analysed the characteristics, surgical outcomes and follow-up data of 21 patients who underwent cerebral revascularization to treat complex VBDAs from 2015 to 2022. According to the location of the aneurysm and the anatomic relationship between the VBDA and the PICA, VBDA patients were classified into four groups: aneurysms located at the VA with PICA involvement (10 patients), aneurysms located at the VA without PICA involvement (1 patient), aneurysms located at the basilar apex segment (1 patient) and aneurysms located at the basilar trunk segment (9 patients). A surgical algorithm for complex VBDAs was determined primarily by the location of the aneurysm, the status of the aneurysm and the ability of retrograde blood flow to reach the proximal vertebrobasilar artery. Surgical modalities for patients with aneurysms in the VA with PICA involvement included low-flow (OA-PICA) bypasses with aneurysm trapping, aneurysm excision or reconstructive clip in 8 patients and STA-PCA bypass combined with PICA preservation and aneurysm trapping in 2 patients. In patients with aneurysms in the VA without PICA involvement, aneurysm excision was performed without cerebral bypass. In patients with aneurysms in the basilar apex segment, high-flow bypass (ECA-RA-P2) with aneurysm trapping was performed. In patients with aneurysms in the basilar trunk segment, surgical modalities included high-flow bypasses (ECA-RA-P2 and LVA-RA-P2) with aneurysm trapping or proximal occlusion in 6 patients, ECA-RA-P2 bypass with partial proximal occlusion in 1 patient, ECA-RA-P2 bypass alone in 1 patient, and STA-PCA bypass with R-VA narrowing in 1 patient. Of the 21 patients, 20 experienced clinical improvement or no change, and 17 of 21 patients achieved favourable functional outcomes (mRS ≤ 2). However, one patient died of infarction and respiratory failure postoperatively. Aneurysms were completely obliterated in 13 patients, shrank in 5 patients and stabilized in 2 patients. The median follow-up period was 32.5 months. During the follow-up period, all bypasses were patent, and further clinical improvement was observed in 11 patients. Cerebral revascularization appears to be safe and effective for the treatment of complex VBDAs, and cerebral revascularization could act as a complementary treatment strategy. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the relationship between use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and incidence of various respiratory and infectious diseases and site-specific fractures. Methods: Large randomized controlled trials (RCTs) of SGLT2is enrolling more than 400 subjects were included. Outcomes of interest were various serious adverse events regarding to respiratory and infectious disorders and site-specific fractures. Meta-analysis was done using risk ratio (RR) and 95% confidence interval (CI) as effect size. Results: Thirty-two large RCTs were included in this meta-analysis. Use of SGLT2is was significantly associated with the lower incidences of 6 kinds of noninfectious respiratory diseases {e.g., Asthma (RR 0.64, 95% CI 0.43–0.96; P = 0.0299), Chronic obstructive pulmonary disease [COPD] (RR 0.75, 95% CI 0.62–0.91; P = 0.0027), and Respiratory failure (RR 0.78, 95% CI 0.61–0.99; P = 0.0447)} and 4 kinds of infectious respiratory diseases {e.g., Bronchitis (RR 0.61, 95% CI 0.46–0.81; P = 0.0007), and Pneumonia (RR 0.85, 95% CI 0.78–0.93; P = 0.0002)}. Use of SGLT2is was not significantly associated with the incidences of 31 kinds of site-specific fractures (e.g., Hip fracture, Femoral neck fracture, and Spinal fracture; P > 0.05). Conclusions: Our meta-analysis confirmed the benefits of SGLT2is against 6 kinds of noninfectious respiratory diseases (e.g., Asthma, COPD, and Respiratory failure) and 4 kinds of infectious respiratory diseases (e.g., Bronchitis, and Pneumonia). These findings suggest a likelihood that SGLT2is might be used to prevent or treat these respiratory diseases. Moreover, our meta-analysis for the first time revealed no association between use of SGLT2is and incidence of various site-specific fractures. [ABSTRACT FROM AUTHOR]

Autoimmune nodopathies are inflammatory diseases of the peripheral nervous system with clinical and neurophysiological peculiar characteristics. In this nosological category, we find patients with autoantibodies against Neurofascin 140/186 and 155, Contactin1, and Caspr1 directed precisely towards nodal and paranodal structures. These antibodies are extremely rare and cause severe clinical symptoms. We describe the clinical case of a patient with autoimmune nodopathy caused by the coexistence of anti-neurofascin (NF) 186/140 and 155, characterized by progressive weakness in all limbs leading to tetraplegia, involving cranial nerves, and respiratory insufficiency. Response to first-line treatments was good followed by rapid dramatic clinical relapse. There are few reported cases of anti-pan NF neuropathy in the literature, and they present a clinical phenotype similar to our patient. In these cases, early recognition of clinical red flags of nodopathies and serial neurophysiological studies can facilitate the diagnosis. However, the severe clinical relapse suggests a possible early use of immunosuppressive therapies for this rare category of patients. [ABSTRACT FROM AUTHOR]

Background: Anti-IgLON5 disease is a rare but potentially reversible cause of cognitive impairment, sleep disturbances, dysautonomia, and movement disorders. It is an autoimmune encephalitis which, due to its insidious onset, could mimic neurodegenerative disorders, and multiple symptoms overlap with those seen in dementia with Lewy bodies (DLB). We hypothesized that the symptomatology and findings in patients with anti-IgLON5 disease overlapped with that of DLB. Objectives: To assess the commonality of features in anti-IgLON5 disease and DLB and identify potential red flags for anti-IgLON5 disease in patients undergoing diagnostic evaluation for DLB. Methods: We searched in MEDLINE, Web of Science, and Embase from inception on December the 8th, 2022 with the search term "IgLON5". We performed a systematic review of case reports and case series of anti-IgLON5 disease, and two reviewers independently extracted data on symptoms and findings. Frequencies of symptoms were compared with consensus criteria for DLB. Results: We included 57 studies with 127 individual case reports of anti-IgLON5 disease (mean age 63 years at diagnosis, median symptom duration 2 years). Cognitive dysfunction was reported in 45% of cases, REM—sleep behavioral disorder in 15%, and 14% had parkinsonism. Respiratory insufficiency was reported in 37%, and bulbar symptoms in 67%. Conclusions: We found a significant overlap between anti-IgLON5 disease and DLB. We propose that anti-IgLON5 disease should be considered in young patients with DLB with chorea, gaze palsy, early dysphagia, or prominent respiratory symptoms. Our study contributes to the emerging knowledge on symptoms and biomarkers in anti-IgLON5 disease. [ABSTRACT FROM AUTHOR]

Background: There are no reports of anesthesia use in adult patients with Silver-Russell syndrome (SRS). Here, we report our experience with anesthesia in an adult patient with SRS complicated by chronic respiratory failure. Case presentation: A 33-year-old woman was clinically diagnosed with SRS. She had severe chronic respiratory failure, complicated by superior mesenteric artery syndrome. Percutaneous gastrostomy was scheduled for nutritional management under epidural anesthesia; however, soon after esophagogastroduodenoscopy was started, she lost consciousness and spontaneous respiration. The patient was urgently intubated and converted to general anesthesia. The end-tidal carbon dioxide tension was > 90 mmHg at intubation. Conclusions: Adult SRS patients with chronic respiratory failure have a risk of CO2 narcosis. SRS also requires preparation for difficult airway management during the perioperative period. [ABSTRACT FROM AUTHOR]

Purpose: COVID-19 patients with respiratory failure frequently require prolonged ventilatory support that would typically warrant early tracheostomy. There has been significant debate on timing, outcomes, and safety of these procedures. The purpose of this study was to determine the epidemiological, hospital, and post-discharge outcomes of this cohort, based on early (ET) versus late (LT) tracheostomy. Methods: Retrospective review (March 2020–January 2021) in a 5-hospital system of ventilated patients who underwent tracheostomy. Demographics, hospital/ICU length of stay (LOS), procedural characteristics, APACHE II scores at ICU admission, stabilization markers, and discharge outcomes were analyzed. Long-term decannulation rates were obtained from long-term acute care facility (LTAC) data. Results: A total of 97 patients underwent tracheostomy (mean 61 years, 62% male, 64% Hispanic). Despite ET being frequently performed during active COVID infection (85% vs. 64%), there were no differences in complication types or rates versus LT. APACHE II scores at ICU admission were comparable for both groups; however, > 50% of LT patients met PEEP stability at tracheostomy. ET was associated with significantly shorter ICU and hospital LOS, ventilator days, and higher decannulation rates. Of the cohort discharged to an LTAC, 59% were ultimately decannulated, 36% were discharged home, and 41% were discharged to a skilled nursing facility. Conclusions: We report the first comprehensive analysis of ET and LT that includes LTAC outcomes and stabilization markers in relation to the tracheostomy. ET was associated with improved clinical outcomes and a short LOS, specifically on days of pre-tracheostomy ventilation and in-hospital decannulation rates. [ABSTRACT FROM AUTHOR]

Background: Pulmonary shunt refers to the passage of venous blood into the arterial blood system bypassing the alveoli-blood gas exchange. Pulmonary shunt is defined by a drop in the physiologic coupling of lung ventilation and lung perfusion. This may consequently lead to respiratory failure. Main body: The pulmonary shunt assessment is often neglected. From a mathematical point of view, pulmonary shunt can be assessed by estimating the degree of mixing between oxygenated and deoxygenated blood. To compute the shunt, three key components are analyzed: the oxygen (O2) content in the central venous blood before gas exchange, the calculated O2 content in the pulmonary capillaries after gas exchange, and the O2 content in the arterial system, after the mixing of shunted and non-shunted blood. Computing the pulmonary shunt becomes of further importance in patients on extracorporeal membrane oxygenation (ECMO), as arterial oxygen levels may not directly reflect the gas exchange of the native lung. Conclusion: In this review, the shunt analysis and its practical clinical applications in different scenarios are discussed by using an online shunt simulator. [ABSTRACT FROM AUTHOR]

Purpose: Paleolithic Diet Fraction (PDF) estimates how large a portion of the absolute dietary intake stems from food groups included in the Paleolithic diet. In randomized controlled trials higher PDFs have been associated with healthier levels of cardiometabolic risk markers. Our aim was to build upon these findings by examining associations between PDF and mortality and incidence of cardiometabolic disease in the prospective Malmö Diet and Cancer Study. Methods: PDF was calculated from an interview-based, modified diet history method, and associations were estimated by using multivariable Cox proportional hazards regression. The examined cohort consisted of 24,104 individuals (44–74 years, 63% women) without previous coronary events, diabetes, or stroke at baseline (1992–1996). A total of 10,092 individuals died during a median follow-up of 18 years. Results: Median PDF was 40% (0–90%). The adjusted hazard ratios (HR) for PDF as a continuous variable (from 0 to 100%) were for risk of death from all causes 0.55 [95% CI 0.45, 0.66], tumor 0.68 [95% CI 0.49, 0.93], cardiovascular 0.55 [95% CI 0.39, 0.78], respiratory 0.44 [95% CI 0.21, 0.90], neurological 0.26 [95% CI 0.11, 0.60], digestive, 0.10 [95% CI 0.03, 0.30], and other diseases 0.64 [95% CI 0.41, 1.00]. The corresponding HR for risk of coronary event was 0.61 [95% 0.43, 0.86], for ischemic stroke it was 0.73 [95% 0.48, 1.09] and for type 2 diabetes it was 0.82 [95% 0.61, 1.10]. Conclusion: Observational data suggest an inverse association between PDF and all-cause as well as cause-specific mortality and incidence of cardiometabolic disease. [ABSTRACT FROM AUTHOR]

Children and adolescents with severe neurological impairment (SNI) require specialized care due to their complex medical needs. In particular, these patients are often affected by severe and recurrent lower respiratory tract infections (LRTIs). These infections, including viral and bacterial etiology, pose a significant risk to these patients, often resulting in respiratory insufficiency and long-term impairments. Using expert consensus, we developed clinical recommendations on the management of LRTIs in children and adolescents with SNI. These recommendations emphasize comprehensive multidisciplinary care and antibiotic stewardship. Initial treatment should involve symptomatic care, including hydration, antipyretics, oxygen therapy, and respiratory support. In bacterial LRTIs, antibiotic therapy is initiated based on the severity of the infection, with aminopenicillin plus a beta-lactamase inhibitor recommended for community-acquired LRTIs and piperacillin-tazobactam for patients with chronic lung disease or tracheostomy. Ongoing management includes regular evaluations, adjustments to antibiotic therapy based on pathogen identification, and optimization of supportive care. Implementation of these recommendations aims to improve the diagnosis and treatment of LRTIs in children and adolescents with SNI. What is Known: • Children and adolescents with severe neurological impairment are particularly affected by severe and recurrent lower respiratory tract infections (LRTIs). • The indication and choice of antibiotic therapy for bacterial LRTI is often difficult because there are no evidence-based treatment recommendations for this heterogeneous but vulnerable patient population; the frequent overuse of broad-spectrum or reserve antibiotics in this patient population increases selection pressure for multidrug-resistant pathogens. What is New: • The proposed recommendations provide a crucial framework for focused diagnostics and treatment of LRTIs in children and adolescents with severe neurological impairment. • Along with recommendations for comprehensive and multidisciplinary therapy and antibiotic stewardship, ethical and palliative care aspects are taken into account. [ABSTRACT FROM AUTHOR]

Introduction: Despite a recognized association between maternal postpartum depression (PPD) and adverse child health outcomes, evidence examining the relationship between PPD symptoms and associated child health service utilization and costs remains unclear. In addition, there is a paucity of evidence describing the relationship between early identification of maternal PPD and associated health service utilization and costs for children. This study aims to address this gap by describing the secondary associations of screening for maternal PPD and annual health service utilization and costs for children over their first five years of life. Methods: Mothers and children enrolled in the prospective All Our Families cohort were linked to provincial administrative data in Alberta, Canada. Multivariable generalized linear models were used to estimate the average annual inpatient, outpatient, physician, and total health service utilization and costs from a public health system perspective for children of mothers screened high risk for PPD, low/moderate risk for PPD, or unscreened. Results: Total mean costs were greatest for children during their first year of life than other years. Those whose mothers were not screened had significantly lower costs compared to those whose mothers were screened low/moderate risk, despite equivalent health service utilization. Discussion: Findings from this study describe the secondary associations of screening for maternal PPD using a public health system perspective. More research is required to fully understand variations in health costs for children across maternal PPD screening categories. Significance: This study describes the relationship between maternal PPD screening status and annual child health service utilization and costs over the first five years of age. Findings from this administrative data study will support decision-makers in understanding the secondary effects associated with maternal PPD screening and inform future cost-effectiveness analyses of PPD screening interventions using a maternal-child health perspective. [ABSTRACT FROM AUTHOR]

Background: Muscle mass evaluation in ICU is crucial since its loss is related with long term complications, including physical impairment. However, quantifying muscle wasting with available bedside tools (ultrasound and bioimpedance analysis) must be more primarily understood. Bioimpedance analysis (BIA) provides estimates of muscle mass and phase angle (PA). The primary aim of this study was to evaluate muscle mass changes with bioimpedance analysis during the first 7 days after ICU admission. Secondary aims searched for correlations between muscular loss and caloric and protein debt. Methods: Patients with an expected ICU-stay ≥ 72 h and the need for artificial nutritional support were evaluated for study inclusion. BIA evaluation of muscle mass and phase angle were performed at ICU admission and after 7 days. Considering the difference between ideal caloric and protein targets, with adequate nutritional macronutrients delivered, we calculated the caloric and protein debt. We analyzed the potential correlation between caloric and protein debt and changes in muscle mass and phase angle. Results: 72 patients from September 1st to October 30th, 2019 and from August 1st to October 30th, 2021 were included in the final statistical analysis. Median age was 68 [59–77] years, mainly men (72%) admitted due to respiratory failure (25%), and requiring invasive mechanical ventilation for 7 [4–10] days. Median ICU stay was 8 [6–12] days. Bioimpedance data at ICU admission and after 7 days showed that MM and PA resulted significantly reduced after 7 days of critically illness, 34.3 kg vs 30.6 kg (p < 0.0001) and 4.90° vs 4.35° (p = 0.0004) respectively. Mean muscle loss was 3.84 ± 6.7 kg, accounting for 8.4% [1–14] MM reduction. Correlation between caloric debt (r = 0.14, p = 0.13) and protein debt (r = 0.18, p = 0.13) with change in MM was absent. Similarly, no correlation was found between caloric debt (r = -0.057, p = 0.631) and protein debt (r = -0.095, p = 0.424) with changes in PA. Conclusions: bioimpedance analysis demonstrated that muscle mass and phase angle were significantly lower after 7 days in ICU. The total amount of calories and proteins does not correlate with changes in muscle mass and phase angle. [ABSTRACT FROM AUTHOR]

Summary: Nivolumab can cause fatal myocarditis. We aimed to analyze the clinical characteristics of nivolumab-induced myocarditis and provide evidence for clinical diagnosis, treatment, and prevention. Studies involving nivolumab-induced myocarditis were identified in electronic databases from 2000 to 2023 for retrospective analysis. A total of 66 patients were included, with a median age of 68 years. The median onset time of myocarditis is 11.5 days. The main organs affected in persons presented with myocarditis are heart (100.0%) and skeletal muscle (22.7%). The main clinical manifestations are dyspnea (49.2%), fatigue (47.6%), and myalgias (25.4%). The levels of troponin, troponin T, troponin I, creatine kinase, creatine kinase myocardial band, creatine phosphokinase, C-reactive protein, brain natriuretic peptide, and N-terminal brain natriuretic peptide precursor were significantly increased. Histopathology often shows lymphocyte infiltration, myocardial necrosis, and fibrosis. Myocardial immunological parameters usually present positive. Cardiac imaging often suggests complete heart block, intraventricular conduction delay, arrhythmia, myocardial infarction, edema, left ventricular ejection fractions reduction, ventricular dysfunction, and other symptoms of myocarditis. Forty-two (63.6%) patients achieved remission within a median time of 8 days after discontinuation of nivolumab and treatment with systemic corticosteroids, immunoglobulins, plasmapheresis, and immunosuppressant. Thirty-five patients eventually died attributed to myocarditis (68.6%), cancer (20.0%), respiratory failure (5.7%), and other reasons (5.7%). Nivolumab-induced myocarditis should be comprehensively diagnosed based on clinical symptoms, histopathological manifestations, immunological parameters, and cardiac function imaging examinations. Nivolumab should be discontinued immediately, plasmapheresis and systemic corticosteroids combined with immunoglobulins or immunosuppressants may be an effective treatment. [ABSTRACT FROM AUTHOR]

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Given the pathophysiology of hypoxemia in patients with Covid-19 acute respiratory failure (ARF), it seemed necessary to evaluate whether ROX index (ratio SpO2/FiO2 to respiratory rate) could accurately predict intubation or death in these patients initially treated by high-flow nasal oxygenation (HFNO). We aimed, therefore, to assess the accuracy of ROX index to discriminate between HFNO failure (sensitivity) and HFNO success (specificity). Methods: We designed a multicentre retrospective cohort study including consecutive patients with Covid-19 ARF. In addition to its accuracy, we assessed the usefulness of ROX index to predict HFNO failure (intubation or death) via logistic regression. Results: Among 218 ARF patients screened, 99 were first treated with HFNO, including 49 HFNO failures (46 intubations, 3 deaths before intubation). At HFNO initiation (H0), ROX index sensitivity was 63% (95%CI 48–77%) and specificity 76% (95%CI 62–87%) using Youden's index. With 4.88 as ROX index cut-off at H12, sensitivity was 29% (95%CI 14–48%) and specificity 90% (95%CI 78–97%). Youden's index yielded 8.73 as ROX index cut-off at H12, with 87% sensitivity (95%CI 70–96%) and 45% specificity (95%CI 31–60%). ROX index at H0 was associated with HFNO failure (p = 0.0005) in univariate analysis. Multivariate analysis showed that SAPS II (p = 0.0003) and radiographic extension of pulmonary injuries (p = 0.0263), rather than ROX index, were predictive of HFNO failure. Conclusions: ROX index cut-off values seem population-specific and the ROX index appears to have a technically acceptable but clinically low capability to discriminate between HFNO failures and successes in Covid-19 ARF patients. In addition, SAPS II and pulmonary injuries at ICU admission appear more useful than ROX index to predict the risk of intubation. [ABSTRACT FROM AUTHOR]

Limited understanding of the immunopathogenesis of human herpesvirus 6B (HHV-6B) has prevented its acceptance as a pulmonary pathogen after hematopoietic cell transplant (HCT). In this prospective multicenter study of patients undergoing bronchoalveolar lavage (BAL) for pneumonia after allogeneic HCT, we test blood and BAL fluid (BALF) for HHV-6B DNA and mRNA transcripts associated with lytic infection and perform RNA-seq on paired blood. Among 116 participants, HHV-6B DNA is detected in 37% of BALs, 49% of which also have HHV-6B mRNA detection. We establish HHV-6B DNA viral load thresholds in BALF that are highly predictive of HHV-6B mRNA detection and associated with increased risk for overall mortality and death from respiratory failure. Participants with HHV-6B DNA in BALF exhibit distinct host gene expression signatures, notable for enriched interferon signaling pathways in participants clinically diagnosed with idiopathic pneumonia. These data implicate HHV-6B as a pulmonary pathogen after allogeneic HCT. Lower respiratory tract disease is a common complication after allogeneic hematopoietic cell transplant (HCT), but underlying reasons remain unclear. Here the authors show that HHV-6B detection in the lungs of allogeneic HCT recipients is associated with increased risk for death and distinct host gene expression profiles, implicating HHV-6B as a pulmonary pathogen in these patients. [ABSTRACT FROM AUTHOR]

Introduction: Dysfunction of the diaphragm may ultimately lead to respiratory insufficiency and compromise patient outcome. Evaluation of diaphragm function is cumbersome. Fluoroscopy has been the gold standard to measure diaphragmatic excursion. Ultrasonography can visualize diaphragm excursion and holds many advantages such as no radiation exposure, increased portability and accessibility. However, correlation between fluoroscopy and ultrasonography has never been studied. We aimed to compare fluoroscopic and ultrasound measures of diaphragm excursion to determine if ultrasonography can replace fluoroscopy. Methods: We performed ultrasound and fluoroscopy simultaneously during sniff inspiration and at total inspiratory capacity in patients with chronic obstructive pulmonary disease, heart failure and in healthy volunteers. Cranio-caudal excursion was measured by fluoroscopy and compared directly to M-mode excursion, B-mode excursion, area change, resting thickness, thickening fraction and contraction velocity measured by ultrasonography. Results: Forty-two participants were included. The Pearson correlation between M-mode and fluoroscopy excursion was 0.61. The slope was 0.9 (90%CI 0.76–1.04) in a regression analysis. Using the Bland–Altman method, the bias was − 0.39 cm (95% CI − 1.04–0.26), p = 0.24. The Pearson correlation between fluoroscopy and B-mode and area change ultrasonography was high; low for thickness and fraction. All correlations were lower during sniff inspiration compared with inspiratory capacity breathing. Conclusion: Ultrasonography has an acceptable correlation and bias compared to fluoroscopy and can thus be used as the primary tool to evaluate diaphragm excursion. [ABSTRACT FROM AUTHOR]

High-flow nasal cannula (HFNC) is a relatively recent therapy that has been used to treat respiratory failure. Until now, the criterion for failure requiring escalation to other forms of ventilatory support has remained unclear. This study evaluated how the ROX index predicts the success or failure of HFNC in infants with bronchiolitis. A prospective, observational, multicenter study was conducted in 2 pediatric ICUs. The data were collected at 7 moments. Patients were categorized into failure and success groups according to HFNC. A total of 102 infants were included, 18(17.6%) of whom failed HFNC therapy. For the ROX index, significant differences were observed between the failure 5.8(95%CI 4.7–7.1) and success 7.7(95%CI 7.2–8.2) groups (p = 0.005) at the 12 h evaluation. According to the analysis of the performance of the ROX index, the AUC at 12 h was 0.716(95%CI 0.591–0.842; p = 0.016). The best cutoff range for the ROX index at 12 h was 6.50–7.18, with a sensitivity of 42% and a specificity of 66% at the cutoff of 6.50, and a sensitivity of 92% and a specificity of 54% at the cutoff of 7.18. We concluded that the ROX index could be effective at predicting the failure of HFNC therapy in infants with bronchiolitis beginning at 12 h after installation. [ABSTRACT FROM AUTHOR]

Introduction: A high proportion of patients with low-risk community-acquired pneumonia (CAP) (classes I-III of the Pneumonia Severity Index) are hospitalized. The purpose of this study was to determine whether validated severity scales are used in clinical practice to make admission decisions, identify the variables that influence this decision, and evaluate the potential predictive value of these variables. Materials and methods: A prospective, observational study of patients ≥ 18 years of age with a diagnosis of low-risk CAP hospitalized or referred from the Emergency Department to outpatient consultations. A multivariate logistic regression predictive model was built to predict the decision to hospitalize a patient. Results: The study population was composed of 1,208 patients (806 inpatients and 402 outpatients). The severity of CAP was estimated in 250 patients (20.7%). The factors that determined hospitalization were "abnormal findings in complementary studies" (643/806: 79.8%; due to respiratory failure in 443 patients) and "signs of clinical deterioration" [64/806 (7.9%): hypotension (16/64, 25%); hemoptoic expectoration (12/64, 18.8%); tachypnea (10/64, 15.6%)]. In total, ambulatory management was not contraindicated in 24.7% of hospitalized patients (199). The predictive model built to decide about hospitalization had a good power of discrimination (AUC 0.876; 95%CI: 0.855–0.897). Conclusions: Scales are rarely used to estimate the severity of CAP at the emergency department. The decision to hospitalize or not a patient largely depends on the clinical experience of the physician. Our predictive model showed a good power to discriminate the patients who required hospitalization. Further studies are warranted to validate these results. [ABSTRACT FROM AUTHOR]

Neonatal respiratory failure (NRF) is an emergency which has not been examined extensively. We critically synthesized the contemporary in-hospital prevalence, mortality rate, predictors, aetiologies, diagnosis and management of NRF to better formulate measures to curb its burden. We searched MEDLINE and Google Scholar from 01/01/1992 to 31/12/2022 for relevant publications. We identified 237 papers from 58 high-income and low-and middle-income countries (LMICs). NRF prevalence ranged from 0.64 to 88.4% with some heterogeneity. The prevalence was highest in Africa, the Middle East and Asia. Globally as well as in Asia and the Americas, respiratory distress syndrome (RDS) was the leading aetiology of NRF. Neonatal sepsis was first aetiology in Africa, whereas in both Europe and the Middle East it was transient tachypnoea of the newborn. Independent predictors of NRF were prematurity, male gender, ethnicity, low/high birth weight, young/advanced maternal age, primiparity/multiparity, maternal smoking, pregestational/gestational diabetes mellitus, infectious anamneses, antepartum haemorrhage, gestational hypertensive disorders, multiple pregnancy, caesarean delivery, antenatal drugs, foetal distress, APGAR score, meconium-stained amniotic fluid and poor pregnancy follow-up. The NRF-related in-hospital mortality rate was 0.21–57.3%, highest in Africa, Asia and the Middle East. This death toll was primarily due to RDS globally and in all regions. Clinical evaluation using the Silverman-Anderson score was widely used and reliable. Initial resuscitation followed by specific management was the common clinical practice. Conclusion: NRF has a high burden globally, driven by RDS, especially in LIMCs where more aggressive treatment and innovations, preferably subsidized, are warranted to curb its alarming burden. What is Known: • Neonatal respiratory failure is a frequent emergency associated with a significant morbidity and mortality, yet there is no comprehensive research paper summarizing its global burden. • Neonatal respiratory failure needs prompt diagnosis and treatment geared at improving neonatal survival. What is New: • Neonatal respiratory failure has an alarmingly high global burden largely attributed to Respiratory distress syndrome. Low resource settings are disproportionately affected by the burden of neonatal respiratory failure. • Independent preditors of neonatal respiratory failure are several but can be classified into foetal, maternal and obstetrical factors. An illustrative pedagogical algorithm is provided to facilitate diagnosis and management of neonatal respiratory failure by healthcare providers. [ABSTRACT FROM AUTHOR]

This correction notice addresses errors in an article titled "Health and Economic Impact of Different Long-Term Oxygen Therapeutic Strategies in Patients with Chronic Respiratory Failure: A French Nationwide Health Claims Database (SNDS) Study." The corrections include fixing a graph, updating percentages in the abstract section, and correcting sentences in the results section. The original article has been corrected. [Extracted from the article]

Background: During Pressure Support Ventilation (PSV) an inspiratory hold allows to measure plateau pressure (Pplat), driving pressure (∆P), respiratory system compliance (Crs) and pressure-muscle-index (PMI), an index of inspiratory effort. This study aims [1] to assess systematically how patient's effort (estimated with PMI), ∆P and tidal volume (Vt) change in response to variations in PSV and [2] to confirm the robustness of Crs measurement during PSV. Methods: 18 patients recovering from acute respiratory failure and ventilated by PSV were cross-randomized to four steps of assistance above (+ 3 and + 6 cmH2O) and below (-3 and -6 cmH2O) clinically set PS. Inspiratory and expiratory holds were performed to measure Pplat, PMI, ∆P, Vt, Crs, P0.1 and occluded inspiratory airway pressure (Pocc). Electromyography of respiratory muscles was monitored noninvasively from body surface (sEMG). Results: As PSV was decreased, Pplat (from 20.5 ± 3.3 cmH2O to 16.7 ± 2.9, P < 0.001) and ∆P (from 12.5 ± 2.3 to 8.6 ± 2.3 cmH2O, P < 0.001) decreased much less than peak airway pressure did (from 21.7 ± 3.8 to 9.7 ± 3.8 cmH2O, P < 0.001), given the progressive increase of patient's effort (PMI from -1.2 ± 2.3 to 6.4 ± 3.2 cmH2O) in line with sEMG of the diaphragm (r = 0.614; P < 0.001). As ∆P increased linearly with Vt, Crs did not change through steps (P = 0.119). Conclusion: Patients react to a decrease in PSV by increasing inspiratory effort—as estimated by PMI—keeping Vt and ∆P on a desired value, therefore, limiting the clinician's ability to modulate them. PMI appears a valuable index to assess the point of ventilatory overassistance when patients lose control over Vt like in a pressure-control mode. The measurement of Crs in PSV is constant—likely suggesting reliability—independently from the level of assistance and patient's effort. [ABSTRACT FROM AUTHOR]

Background: In the last decade, Ibrutinib has become the standard of care in the treatment of several lymphoproliferative diseases such as chronic lymphocytic leukemia (CLL) and several non-Hodgkin lymphoma. Beyond Bruton tyrosine kinase inhibition, Ibrutinib shows broad immunomodulatory effects that may promote the occurrence of infectious complications, including opportunistic infections. The infectious burden has been shown to vary by disease status, neutropenia, and prior therapy but data focusing on severe infections requiring intensive care unit (ICU) admission remain scarce. We sought to investigate features and outcomes of severe infections in a multicenter cohort of 69 patients receiving ibrutinib admitted to 10 French intensive care units (ICU) from 1 January 2015 to 31 December 2020. Results: Median time from ibrutinib initiation was 6.6 [3–18] months. Invasive fungal infections (IFI) accounted for 19% (n = 13/69) of severe infections, including 9 (69%; n = 9/13) invasive aspergillosis, 3 (23%; n = 3/13) Pneumocystis pneumonia, and 1 (8%; n = 1/13) cryptococcosis. Most common organ injury was acute respiratory failure (ARF) (71%; n = 49/69) and 41% (n = 28/69) of patients required mechanical ventilation. Twenty (29%; n = 20/69) patients died in the ICU while day-90 mortality reached 55% (n = 35/64). In comparison with survivors, decedents displayed more severe organ dysfunctions (SOFA 7 [5–11] vs. 4 [3–7], p = 0.004) and were more likely to undergo mechanical ventilation (68% vs. 31%, p = 0.010). Sixty-three ibrutinib-treated patients were matched based on age and underlying malignancy with 63 controls receiving conventional chemotherapy from an historic cohort. Despite a higher median number of prior chemotherapy lines (2 [1–2] vs. 0 [0–2]; p < 0.001) and higher rates of fungal [21% vs. 8%, p = 0.001] and viral [17% vs. 5%, p = 0.027] infections in patients receiving ibrutinib, ICU (27% vs. 38%, p = 0.254) and day-90 mortality (52% vs. 48%, p = 0.785) were similar between the two groups. Conclusion: In ibrutinib-treated patients, severe infections requiring ICU admission were associated with a dismal prognosis, mostly impacted by initial organ failures. Opportunistic agents should be systematically screened by ICU clinicians in this immunocompromised population. [ABSTRACT FROM AUTHOR]

Rationale: Novel synthetic opioids (NSOs) are emerging in recreational drug markets worldwide. In particular, 2-benzylbenzimidazole 'nitazene' compounds are problematic NSOs associated with serious clinical consequences, including fatal respiratory depression. Evidence from in vitro studies shows that alkoxy chain length can influence the potency of nitazenes at the mu-opioid receptor (MOR). However, structure–activity relationships (SARs) of nitazenes for inducing opioid-like effects in animal models are not well understood compared to relevant opioids contributing to the ongoing opioid crisis (e.g., fentanyl). Objectives: Here, we examined the in vitro and in vivo effects of nitazene analogues with varying alkoxy chain lengths (i.e., metonitazene, etonitazene, isotonitazene, protonitazene, and butonitazene) as compared to reference opioids (i.e., morphine and fentanyl). Methods and Results: Nitazene analogues displayed nanomolar affinities for MOR in rat brain membranes and picomolar potencies to activate MOR in transfected cells. All compounds induced opioid-like effects on locomotor activity, hot plate latency, and body temperature in male mice, and alkoxy chain length markedly influenced potency. Etonitazene, with an ethoxy chain, was the most potent analogue in MOR functional assays (EC50 = 30 pM, Emax = 103%) and across all in vivo endpoints (ED50 = 3–12 μg/kg). In vivo SARs revealed that ethoxy, isopropoxy, and propoxy chains engendered higher potencies than fentanyl, whereas methoxy and butoxy analogues were less potent. MOR functional potencies, but not MOR affinities, were positively correlated with in vivo potencies to induce opioid effects. Conclusions: Overall, our data show that certain nitazene NSOs are more potent than fentanyl as MOR agonists in mice, highlighting concerns regarding the high potential for overdose in humans who are exposed to these compounds. [ABSTRACT FROM AUTHOR]

Background: Guillain-Barré syndrome (GBS) is an acute inflammatory neuropathy. The Erasmus GBS Respiratory Insufficiency Score (EGRIS) and the modified Erasmus GBS Outcome Score (mEGOS) are prognostic models used in the prediction of mechanical ventilation and outcome. Thus far, there are only few biomarkers for the prognosis prediction of GBS patients, and albumin level is one that is promising. Methods: Patients diagnosed with GBS from 2013 to 2022 at Renmin Hospital, Wuhan University, China, were included. Patients hospitalized between 2016 and 2022 underwent short- and long-term follow-ups. The correlations between EGRIS/mEGOS and mechanical ventilation and outcome were evaluated. Serum albumin level was examined the day after admission. Furthermore, we also investigated whether the level of serum albumin was useful in predicting disease severity or poor outcome. Results: In all, 145 patients were enrolled. Nineteen patients (13.1%) who required mechanical ventilation had higher Hughes GBS disability score (HGDS) at admission and discharge (P < 0.05 and P < 0.0001, respectively), shorter time from onset to admission and treatment (P < 0.01 and P < 0.001, respectively) and longer hospital stays (P < 0.001) than patients who did not require mechanical ventilation. High EGRIS scores were linked with the need for mechanical ventilation (r = 0.427, P < 0.001, AUC = 0.623). Seventy-one patients were admitted between 2016 and 2022. Of these, 65 patients had a 4-week follow-up and 61 had a 6-month follow-up. Higher mEGOS scores at admission and 7 days after admission significantly correlated with short- (P < 0.0001 and P < 0.0001) and long-term (P < 0.05 and P < 0.05) outcomes, respectively. No significant difference in outcome was found between different subtypes (4 weeks [P = 0.099] and 6 months [P = 0.172]). Patients with lower albumin level tended to have higher HGDS (at admission P < 0.05, at nadir P < 0.001, and at discharge P < 0.001) and higher properties of the need of mechanical ventilation (P < 0.05) and ICU stay (P < 0.05) than those with normal albumin levels. Those with low albumin levels were also unable to walk independently at 6 months (P < 0.01). Conclusions: mEGOS scores predicted the outcomes of GBS patients in China, and EGRIS score predicted the need for mechanical ventilation in these patients. Albumin level at admission correlated well with disease severity and outcomes. [ABSTRACT FROM AUTHOR]

This paper reports the proceedings of a meeting convened by the Research Group on Thoracic Ultrasound in Older People of the Italian Society of Gerontology and Geriatrics, to discuss the current state-of-the-art of clinical research in the field of geriatric thoracic ultrasound and identify unmet research needs and potential areas of development. In the last decade, point-of-care thoracic ultrasound has entered clinical practice for diagnosis and management of several respiratory illnesses, such as bacterial and viral pneumonia, pleural effusion, acute heart failure, and pneumothorax, especially in the emergency–urgency setting. Very few studies, however, have been specifically focused on older patients with frailty and multi-morbidity, who frequently exhibit complex clinical pictures needing multidimensional evaluation. At the present state of knowledge, there is still uncertainty on the best requirements of ultrasound equipment, methodology of examination, and reporting needed to optimize the advantages of thoracic ultrasound implementation in the care of geriatric patients. Other issues regard differential diagnosis between bacterial and aspiration pneumonia, objective grading of interstitial syndrome severity, quantification and monitoring of pleural effusions and solid pleural lesions, significance of ultrasonographic assessment of post-COVID-19 sequelae, and prognostic value of assessment of diaphragmatic thickness and motility. Finally, application of remote ultrasound diagnostics in the community and nursing home setting is still poorly investigated by the current literature. Overall, the presence of several open questions on geriatric applications of thoracic ultrasound represents a strong call to implement clinical research in this field. [ABSTRACT FROM AUTHOR]

Copyright of Medizinische Klinik: Intensivmedizin & Notfallmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)