First-year outcomes of very low birth weight preterm singleton infants with hypoxemic respiratory failure treated with milrinone and inhaled nitric oxide (iNO) compared to iNO alone: A nationwide retrospective study.

BACKGROUND: Inhaled nitric oxide (iNO) has a beneficial effect on hypoxemic respiratory failure. The increased use of concurrent iNO and milrinone was observed. We aimed to report the trends of iNO use in the past 15 years in Taiwan and compare the first-year outcomes of combining iNO and milrinone to the iNO alone in very low birth weight preterm (VLBWP) infants under mechanical ventilation. METHODS: This nationwide cohort study enrolled preterm singleton infants with birth weight <1500g treated with iNO from 2004 to 2019. Infants were divided into two groups, with a combination of intravenous milrinone (Group 2, n = 166) and without milrinone (Group 1, n = 591). After propensity score matching (PSM), each group's sample size is 124. The primary outcomes were all-cause mortality and the respiratory condition, including ventilator use and duration. The secondary outcomes were preterm morbidities within one year after birth. RESULTS: After PSM, more infants in Group 2 needed inotropes. The mortality rate was significantly higher in Group 2 than in Group 1 from one month after birth till 1 year of age (55.1% vs. 13.5%) with the adjusted hazard ratio of 4.25 (95%CI = 2.42-7.47, p <0.001). For infants who died before 36 weeks of postmenstrual age (PMA), Group 2 had longer hospital stays compared to Group 1. For infants who survived after 36 weeks PMA, the incidence of moderate and severe bronchopulmonary dysplasia (BPD) was significantly higher in Group 2 than in Group 1. For infants who survived until one year of age, the incidence of pneumonia was significantly higher in Group 2 (28.30%) compared to Group 1 (12.62%) (p = 0.0153). CONCLUSION: Combined treatment of iNO and milrinone is increasingly applied in VLBWP infants in Taiwan. This retrospective study did not support the benefits of combining iNO and milrinone on one-year survival and BPD prevention. A future prospective study is warranted.

SCARLET (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial): study protocol for a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 trial of i.v. citicoline (CDP-choline) in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure.

BACKGROUND: The SARS CoV-2 pandemic has resulted in more than 1.1 million deaths in the USA alone. Therapeutic options for critically ill patients with COVID-19 are limited. Prior studies showed that post-infection treatment of influenza A virus-infected mice with the liponucleotide CDP-choline, which is an essential precursor for de novo phosphatidylcholine synthesis, improved gas exchange and reduced pulmonary inflammation without altering viral replication. In unpublished studies, we found that treatment of SARS CoV-2-infected K18-hACE2-transgenic mice with CDP-choline prevented development of hypoxemia. We hypothesize that administration of citicoline (the pharmaceutical form of CDP-choline) will be safe in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure (HARF) and that we will obtain preliminary evidence of clinical benefit to support a larger Phase 3 trial using one or more citicoline doses. METHODS: We will conduct a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 dose-ranging and safety study of Somazina® citicoline solution for injection in consented adults of any sex, gender, age, or ethnicity hospitalized for SARS CoV-2-associated HARF. The trial is named "SCARLET" (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial). We hypothesize that SCARLET will show that i.v. citicoline is safe at one or more of three doses (0.5, 2.5, or 5 mg/kg, every 12 h for 5 days) in hospitalized SARS CoV-2-infected patients with HARF (20 per dose) and provide preliminary evidence that i.v. citicoline improves pulmonary outcomes in this population. The primary efficacy outcome will be the SpO2:FiO2 ratio on study day 3. Exploratory outcomes include Sequential Organ Failure Assessment (SOFA) scores, dead space ventilation index, and lung compliance. Citicoline effects on a panel of COVID-relevant lung and blood biomarkers will also be determined. DISCUSSION: Citicoline has many characteristics that would be advantageous to any candidate COVID-19 therapeutic, including safety, low-cost, favorable chemical characteristics, and potentially pathogen-agnostic efficacy. Successful demonstration that citicoline is beneficial in severely ill patients with SARS CoV-2-induced HARF could transform management of severely ill COVID patients. TRIAL REGISTRATION: The trial was registered at www. CLINICALTRIALS: gov on 5/31/2023 (NCT05881135). TRIAL STATUS: Currently enrolling.

The effect of antifibrotic agents on acute respiratory failure in COVID-19 patients: a retrospective cohort study from TriNetX US collaborative networks.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on global health and economies, resulting in millions of infections and deaths. This retrospective cohort study aimed to investigate the effect of antifibrotic agents (nintedanib and pirfenidone) on 1-year mortality in COVID-19 patients with acute respiratory failure. METHODS: Data from 61 healthcare organizations in the TriNetX database were analyzed. Adult patients with COVID-19 and acute respiratory failure were included. Patients with a pre-existing diagnosis of idiopathic pulmonary fibrosis before their COVID-19 diagnosis were excluded. The study population was divided into an antifibrotic group and a control group. Propensity score matching was used to compare outcomes, and hazard ratios (HR) for 1-year mortality were calculated. RESULTS: The antifibrotic group exhibited a significantly lower 1-year mortality rate compared to the control group. The survival probability at the end of the study was 84.42% in the antifibrotic group and 69.87% in the control group. The Log-Rank test yielded a p-value of less than 0.001. The hazard ratio was 0.434 (95% CI: 0.264-0.712), indicating a significant reduction in 1-year mortality in the antifibrotic group. Subgroup analysis demonstrated significantly improved 1-year survival in patients receiving nintedanib treatment and during periods when the Wuhan strain was predominant. DISCUSSION: This study is the first to demonstrate a survival benefit of antifibrotic agents in COVID-19 patients with acute respiratory failure. Further research and clinical trials are needed to confirm the efficacy of these antifibrotic agents in the context of COVID-19 and acute respiratory failure.

Oral decitabine and cedazuridine plus venetoclax for older or unfit patients with acute myeloid leukaemia: a phase 2 study.

BACKGROUND: Hypomethylating agents combined with venetoclax are effective regimens in patients with acute myeloid leukaemia who are ineligible for intensive chemotherapy. Decitabine and cedazuridine (ASTX727) is an oral formulation of decitabine that achieves equivalent area-under-curve exposure to intravenous decitabine. We performed a single centre phase 2 study to evaluate the efficacy and safety of ASTX727 plus venetoclax. METHODS: This study enrolled patients with newly diagnosed (frontline treatment group) acute myeloid leukaemia who were ineligible for intensive chemotherapy (aged ≥75 years, an Eastern Cooperative Oncology Group [ECOG] performance status of 2-3, or major comorbidities) or relapsed or refractory acute myeloid leukaemia. Being aged 18 years or older and having an ECOG performance status of 2 or less were requirements for the relapsed or refractory disease treatment cohort, without any limits in the number of previous lines of therapy. Treatment consisted of ASTX727 (cedazuridine 100 mg and decitabine 35 mg) orally for 5 days and venetoclax 400 mg orally for 21-28 days in 28-day cycles. The primary outcome was overall response rate of ASTX727 plus venetoclax. Living patients who have not completed cycle one were not evaluable for response. Safety was analysed in all patients who started treatment. This study was registered on ClinicalTrials.gov (NCT04746235) and is ongoing. The data cutoff date for this analysis was Sept 22, 2023. FINDINGS: Between March 16, 2021, and Sept 18, 2023, 62 patients were enrolled (49 frontline and 13 relapsed or refractory) with a median age of 78 years (IQR 73-82). 36 (58%) were male; 53 (85%) were White, 4 (6%) Black, 2 (3%) Asian and 3 (5%) other or did not answer. 48 (77%) of 62 patients were European LeukemiaNet 2022 adverse risk, 24 (39%) had antecedent myelodysplastic syndromes, 12 (19%) had previously failed a hypomethylating agent, ten (16%) had therapy-related acute myeloid leukaemia, and 11 (18%) had TP53 mutations. The median follow-up time was 18·3 months (IQR 8·8-23·3). The overall response rate was 30 (64%) of 47 patients (95% CI 49-77) in frontline cohort and six (46%) of 13 patients (19-75) in relapsed or refractory cohort. The most common grade 3 or worse treatment-emergent adverse events were febrile neutropenia in 11 (18%) of 62 patients, pneumonia in eight (13%), respiratory failure in five (8%), bacteraemia in four (6%), and sepsis in four (6%). Three deaths occurred in patients in remission (one sepsis, one gastrointestinal haemorrhage, and one respiratory failure) and were potentially treatment related. INTERPRETATION: ASTX727 plus venetoclax is an active fully oral regimen and safe in most older or unfit patients with acute myeloid leukaemia. Our findings should be confirmed in larger multicentric studies. FUNDING: MD Anderson Cancer Center Support Grant, Myelodysplastic Syndrome/Acute Myeloid Leukaemia Moon Shot, Leukemia SPORE, Taiho Oncology, and Astex Pharmaceuticals.

Serotonin therapies for opioid-induced disordered swallow and respiratory depression.

Opioids are well-known to cause respiratory depression, but despite clinical evidence of dysphagia, the effects of opioids on swallow excitability and motor pattern are unknown. We tested the effects of the clinically relevant opioid buprenorphine on pharyngeal swallow and respiratory drive in male and female rats. We also evaluated the utility of 5-HT1A agonists (8-OH-DPAT and buspirone) to improve swallowing and breathing following buprenorphine administration. Experiments were performed on 44 freely breathing Sprague-Dawley rats anesthetized with sodium pentobarbital. Bipolar fine wire electrodes were inserted into the mylohyoid, thyroarytenoid, posterior cricoarytenoid, thyropharyngeus, and diaphragm muscles to measure electromyographic (EMG) activity of swallowing and breathing. We evaluated the hypotheses that swallowing varies by stimulus, opioids depress swallowing and breathing, and that 5-HT1A agonists improve these depressions. Our results largely confirmed the following hypotheses: 1) swallow-related EMG activity was larger during swallows elicited by esophageal distension plus oral water infusion than by either stimulus alone. 2) Buprenorphine depressed swallow in both sexes, but females were more susceptible to total swallow suppression. 3) Female animals were also more vulnerable to opioid-induced respiratory depression. 4) 8-OH-DPAT rescued breathing following buprenorphine-induced respiratory arrest, and pretreatment with the partial 5-HT1A agonist buspirone prevented buprenorphine-induced respiratory arrest in female animals. 5) 8-OH-DPAT enhanced mylohyoid and thyropharyngeus EMG amplitude during swallow but did not restore excitability of the swallow pattern generator following total suppression by buprenorphine. Our results highlight sex-specific and behavior-specific effects of buprenorphine and provide preclinical evidence of a 5HT1A agonist for the treatment of respiratory depression and dysphagia.NEW & NOTEWORTHY This is the first study, to our knowledge, to evaluate sex-specific effects of opioid administration on pharyngeal swallow. We expand on a small but growing number of studies that report a lower threshold for opioid-induced respiratory depression in females compared with males, and we are the first to produce this effect with the partial µ-opioid-receptor agonist buprenorphine. This is the first demonstration, to our knowledge, that activation of 5-HT1A receptors can improve swallow and breathing outcomes following systemic buprenorphine administration.

Afatinib treatment of severe respiratory failure due to malignant lymphangitis in a dialysis patient with squamous cell carcinoma of the lung.

Patients on dialysis have limited treatment options for advanced lung cancer because some chemotherapeutic agents are unavailable due to renal dysfunction. A man in his 70s on peritoneal dialysis presented with persistent fever refractory to antibiotics for 2 weeks. Subsequent whole-body CT showed a 5 cm diameter mass in the right lower lobe of the lung with right-sided pleural effusion and osteolytic metastasis of the right iliac bone. The patient was diagnosed with squamous cell carcinoma (cT3N2M1b, stage IVB) harbouring the p.Gly719Ala point mutation on exon 18 of the epidermal growth factor receptor. The patient developed severe respiratory failure due to malignant lymphangitis after a bronchoscopy. He received 30 mg/day of afatinib, resulting in tumour shrinkage and recovery from respiratory failure. We advocate for aggressive screening of driver oncogenes in patients with lung cancer on dialysis, including those with squamous cell lung cancer.

Epidemiology and outcomes of multidrug-resistant bacterial infection in non-cystic fibrosis bronchiectasis.

PURPOSE: Multidrug-resistant (MDR) bacteria impose a considerable health-care burden and are associated with bronchiectasis exacerbation. This study investigated the clinical outcomes of adult patients with bronchiectasis following MDR bacterial infection. METHODS: From the Chang Gung Research Database, we identified patients with bronchiectasis and MDR bacterial infection from 2008 to 2017. The control group comprised patients with bronchiectasis who did not have MDR bacterial infection and were propensity-score matched at a 1:2 ratio. The main outcomes were in-hospital and 3-year mortality. RESULTS: In total, 554 patients with both bronchiectasis and MDR bacterial infection were identified. The types of MDR bacteria that most commonly affected the patients were MDR- Acinetobacter baumannii (38.6%) and methicillin-resistant Staphylococcus aureus (18.4%), Extended-spectrum-beta-lactamases (ESBL)- Klebsiella pneumoniae (17.8%), MDR-Pseudomonas (14.8%), and ESBL-E. coli (7.5%). Compared with the control group, the MDR group exhibited lower body mass index scores, higher rate of chronic bacterial colonization, a higher rate of previous exacerbations, and an increased use of antibiotics. Furthermore, the MDR group exhibited a higher rate of respiratory failure during hospitalization (MDR vs. control, 41.3% vs. 12.4%; p < 0.001). The MDR and control groups exhibited in-hospital mortality rates of 26.7% and 7.6%, respectively (p < 0.001); 3-year respiratory failure rates of 33.5% and 13.5%, respectively (p < 0.001); and 3-year mortality rates of 73.3% and 41.5%, respectively (p < 0.001). After adjustments were made for confounding factors, the infection with MDR and MDR bacteria species were determined to be independent risk factors affecting in-hospital and 3-year mortality. CONCLUSIONS: MDR bacteria were discovered in patients with more severe bronchiectasis and were independently associated with an increased risk of in-hospital and 3-year mortality. Given our findings, we recommend that clinicians identify patients at risk of MDR bacterial infection and follow the principle of antimicrobial stewardship to prevent the emergence of resistant bacteria among patients with bronchiectasis.

Standard of care plus telmisartan on respiratory failure due to COVID-19 (STAR-COVID trial).

BACKGROUND: The potential influence of renin-angiotensin inhibitors on the severity of SARS-CoV-2 infection has been considered in preclinical and observational studies with contradictory results. Therefore, we investigated the effect of telmisartan in reducing lung injury among hospitalized COVID-19 patients. METHODS: The STAR-COVID trial was conducted as a prospective, parallel-group, randomized, open-label study involving hospitalized adult patients with severe COVID-19 (NCT04510662). Sixty-six patients were enrolled: 33 were assigned to the telmisartan group and 33 to the control group. The mean age of participants was 48.8 years, with 62.5% being male. Participants were randomly assigned in a 1:1 ratio to receive either telmisartan (40 mg daily for 14 days or until discharge) plus standard of care or standard of care alone. The primary outcome assessed was the initiation of mechanical ventilation within 14 days. Secondary outcomes included 30-day mortality, the need for vasopressors, hemodialysis requirements, and length of hospital stay. RESULTS: Comparison between the telmisartan group and the control group revealed no significant difference in the occurrence of mechanical ventilation at 14 days (25% with telmisartan vs. 18.7% with control, P=0.579). Additionally, there were no significant differences observed in terms of mortality (25% vs. 21.9%, P=0.768), the need for vasopressors (18.8% in both groups, P=1.000), hemodialysis requirements (6.3% vs. 3.1%, P=0.500), and length of hospital stay (median of 7 days in both groups, P=0.962). CONCLUSIONS: Compared with the standard of care, telmisartan therapy demonstrated no significant impact on respiratory failure in hospitalized patients with severe COVID-19.

Real-World Effectiveness Study of Nirmatrelvir-Ritonavir or Molnupiravir in Hospitalized Unvaccinated Patients with Chronic Respiratory Diseases and Moderate COVID-19 at Presentation.

Introduction: Nirmatrelvir-ritonavir (NMV-r) and molnupiravir (MOL) were developed as out-patient anti-viral for mild COVID-19. There was limited data on their role in treating COVID-19 for hospitalized patients, especially among adult patients who are unvaccinated and had chronic respiratory diseases. Methods: A territory-wide retrospective study was conducted in Hong Kong to compare the efficacy of NMV-r and MOL against COVID-19 in unvaccinated adult patients with asthma, chronic obstructive pulmonary disease, bronchiectasis and interstitial lung diseases presenting with moderate COVID-19 from 16th February 2022 to 15th March 2023. Results: A total of 1354 patients were included, 738 received NMV-r and 616 received MOL. NMV-r was more effective in reducing 90-day mortality with adjusted hazard ratios (aHR) of 0.508 (95% confidence interval [CI] = 0.314-0.822, p = 0.006). Patients who received NMV-r also had significantly shorter length of stay (LOS) than those receiving MOL, with median LOS of 4 (Interquartile range [IQR] = 2-7) for NMV-r and 6 (IQR = 3-10) for MOL (p-value < 0.001). There was no statistically significant difference in the development of respiratory failure and severe respiratory failure in the two groups. Discussion: NMV-r was more effective than MOL among unvaccinated adults with chronic respiratory diseases who were hospitalized for moderate COVID-19 without hypoxaemia on admission.

Prophylactic Oropharyngeal Surfactant for Preterm Newborns at Birth: A Randomized Clinical Trial.

Importance: Preterm newborns at risk of respiratory distress syndrome are supported with continuous positive airway pressure (CPAP). Many newborns worsen despite CPAP and are intubated for surfactant administration, an effective therapy for treatment of respiratory distress syndrome. Endotracheal intubation is associated with adverse effects. Pharyngeal administration of surfactant to preterm animals and humans has been reported as an alternative. Objective: To assess whether giving prophylactic oropharyngeal surfactant to preterm newborns at birth would reduce the rate of intubation for respiratory failure. Design, Setting, and Participants: This unblinded, parallel-group randomized clinical trial (Prophylactic Oropharyngeal Surfactant for Preterm Infants [POPART]) was conducted from December 17, 2017, to September 11, 2020, at 9 tertiary neonatal intensive care units in 6 European countries. Newborns born before 29 weeks of gestation without severe congenital anomalies, for whom intensive care was planned, were eligible for inclusion. The data were analyzed from July 27, 2022, to June 20, 2023. Intervention: Newborns were randomly assigned to receive oropharyngeal surfactant at birth in addition to CPAP or CPAP alone. Randomization was stratified by center and gestational age (GA). Main Outcomes and Measures: The primary outcome was intubation in the delivery room for bradycardia and/or apnea or in the neonatal intensive care unit for prespecified respiratory failure criteria within 120 hours of birth. Caregivers were not masked to group assignment. Results: Among 251 participants (mean [SD] GA, 26 [1.5] weeks) who were well matched at study entry, 126 (69 [54.8%] male) with a mean (SD) birth weight of 858 (261) grams were assigned to the oropharyngeal surfactant group, and 125 (63 [50.4%] male) with a mean (SD) birth weight of 829 (253) grams were assigned to the control group. The proportion of newborns intubated within 120 hours was not different between the groups (80 [63.5%) in the oropharyngeal surfactant group and 81 [64.8%] in the control group; relative risk, 0.98 [95% CI, 0.81-1.18]). More newborns assigned to the oropharyngeal surfactant group were diagnosed with and treated for pneumothorax (21 [16.6%] vs 8 [6.4%]; P = .04). Conclusions and Relevance: This randomized clinical trial found that administration of prophylactic oropharyngeal surfactant to newborns born before 29 weeks' GA did not reduce the rate of intubation in the first 120 hours of life. These findings suggest that administration of surfactant into the oropharynx immediately after birth in addition to CPAP should not be routinely used. Trial Registration: EudraCT: 2016-004198-41.

Remimazolam and Remifentanil Use Induced Severe Respiratory Depression and Laryngeal Spasm During Intravenous Sedation and Analgesia: A Case Report.

INTRODUCTION: Intravenous sedation and analgesia are widely used in minor surgeries. Remifentanil and remimazolam are advantageous in this setting because of their rapid onset of action, and short duration of action leading to a rapid recovery. However, the two drugs combined need to be titrated to avoid airway-related adverse events. CASE PRESENTATION: This article reports a case of severe respiratory depression and severe laryngeal spasm induced by remifentanil and remimazolam when they were used for analgesia and sedation in a patient undergoing oral biopsy. CONCLUSION: We aim to improve awareness about the safety of these drugs among anesthesiologists and increase their ability to manage the risk associated with their use.

Palatal prolapse during nasal expiration in patients with myasthenia gravis.

INTRODUCTION/AIMS: We have encountered patients with myasthenia gravis (MG) who exhibited palatal prolapse (PP) during nasal expiration in the supine position while awake. This may be an overlooked cause of dyspnea in MG patients. This study aimed to examine and describe the characteristics of MG patients with PP. METHODS: We reviewed the medical records of 183 consecutive patients who were diagnosed with MG in our hospital from 2012 to 2021. Thirty-two patients underwent laryngoscopy because of bulbar symptoms. Eight of these patients (25%) exhibited PP on laryngoscopy. Clinical features of these eight patients were retrospectively characterized. RESULTS: Median age of the eight patients with PP was 70 years. Six were men. Median body mass index was 21.6 kg/m2 . All patients exhibited PP in the supine position but not the sitting position. Although no patient had abnormal findings on spirometry nor chest computed tomography, six reported dyspnea or difficulty with nasal expiration only in the supine position. PP improved in all four patients who underwent edrophonium testing. All eight patients eventually improved after immunotherapy. DISCUSSION: PP during nasal expiration may be a cause of dyspnea in MG patients, along with respiratory muscle impairment, lung disease, and vocal cord paralysis. Laryngoscopy in the supine position is required to confirm.

The Effect of Dezocine on the Median Effective Dose of Sufentanil-Induced Respiratory Depression in Patients Undergoing Spinal Anesthesia Combined with Low-Dose Dexmedetomidine.

Purpose: The application of sedation and analgesia in spinal anesthesia has many benefits, but the risk of respiratory depression (RD) caused by opioids cannot be ignored. We aimed to observe the effect of dezocine, a partial agonist of µ-receptor, on the median effective dose (ED50) of sufentanil-induced RD in patients undergoing spinal anesthesia combined with low-dose dexmedetomidine. Patients and Methods: Sixty-two patients were randomly assigned to dezocine group (DS) and control group (MS). After spinal anesthesia, mask oxygen (5 L/min) and dexmedetomidine (0.1 ug/kg) were given. Five minutes later, patients in the DS group received an Intravenous (IV) bolus of sufentanil and 0.05mg/kg dezocine, while patients in the MS group only received an IV bolus of sufentanil. Results: ED50 of DS group was 0.342 ug/kg, 95% confidence interval (CI) was (0.269, 0.623) ug/kg, and the ED50 of MS group was 0.291 ug/kg, 95% CI was (0.257, 0.346) ug/kg. There was no difference in the type and treatment measures of RD and hemodynamic changes between the two groups, and no serious adverse reactions occurred in either group. Conclusion: Dezocine can improve RD induced by sufentanil in patients with spinal anesthesia combined with low-dose dexmedetomidine, and increase the safety window of sufentanil use.

Investigation of monoclonal antibody CSX-1004 for fentanyl overdose.

The opioid crisis in the United States is primarily driven by the highly potent synthetic opioid fentanyl leading to >70,000 overdose deaths annually; thus, new therapies for fentanyl overdose are urgently needed. Here, we present the first clinic-ready, fully human monoclonal antibody CSX-1004 with picomolar affinity for fentanyl and related analogs. In mice CSX-1004 reverses fentanyl antinociception and the intractable respiratory depression caused by the ultrapotent opioid carfentanil. Moreover, toxicokinetic evaluation in a repeat-dose rat study and human tissue cross-reactivity study reveals a favorable pharmacokinetic profile of CSX-1004 with no safety-related issues. Using a highly translational non-human primate (NHP) model of respiratory depression, we demonstrate CSX-1004-mediated protection from repeated fentanyl challenges for 3-4 weeks. Furthermore, treatment with CSX-1004 produces up to a 15-fold potency reduction of fentanyl in NHP respiration, antinociception and operant responding assays without affecting non-fentanyl opioids like oxycodone. Taken together, our data establish the feasibility of CSX-1004 as a promising candidate medication for preventing and reversing fentanyl-induced overdose.

Prone versus lateral position in acute hypoxemic respiratory failure patients with HFNO therapy: study protocol for a multicentre randomised controlled open-label trial.

BACKGROUND: High-flow nasal oxygen (HFNO) therapy is a leading treatment technique for acute hypoxemic respiratory failure (AHRF), but its treatment failure rate remains high. The awake prone position (APP) has been proven to increase oxygenation and reduce the endotracheal intubation rate in patients with COVID-19-induced AHRF. However, the APP is poorly tolerated in patients, and its performance in improving prognoses is controversial. The lateral position has a similar mechanism and effect to the prone position, but it is more tolerable than the prone position. Therefore, it is worth exploring whether the lateral position is better for awake patients with AHRF. METHODS: This is a protocol for a three-arm parallel-group multicentre randomised controlled open-label exploratory trial. A total of 583 patients from two hospitals in Chongqing, China, will be randomised to take the semi-recumbent position, lateral position, or prone position at a ratio of 1:1:1. Patients are all diagnosed with AHRF secondary to non-COVID-19 pneumonia or lung infection and receiving HFNO therapy. The primary outcome is ventilator-free days in 28 days. The secondary outcomes are the 28-day intubation rate, 28-day all-cause mortality, total position change time, the incidence of adverse events, number of hours using HFNO therapy, length of hospital and intensive care unit (ICU) stay, and others. We will conduct subgroup analyses on the arterial partial pressure of oxygen to the fraction of inspiration oxygen (PaO2/FiO2) ratio (> 200 mmHg or ≤ 200 mmHg), time from admission to intervention implementation (< 24 h or ≥ 24 h), position changing time, and different diagnoses. DISCUSSION: This trial will explore the prognostic effects of the APP with that of the lateral position in awake patients with non-COVID-19AHRF and compare the differences between them. To provide evidence for clinical decision-making and further research on position management. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry. The registration number is ChiCTR2200055822 . Registered on January 20, 2022.

Nusinersen for Spinal Muscular Atrophy Type I with Chronic Respiratory Failure: A Retrospective Study in South Korea.

PURPOSE: To analyze the efficacy and safety of nusinersen in patients with spinal muscular atrophy (SMA) type I with chronic respiratory failure. MATERIALS AND METHODS: We retrospectively reviewed seven patients diagnosed with SMA type I and chronic respiratory failure who were on permanent ventilation and treated with nusinersen at Gangnam Severance Hospital between January 2018 and July 2023. Patient demographics and clinical characteristics were recorded, and treatment progress was evaluated according to Hammersmith Infant Neurological Examination (HINE-2) and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scores. RESULTS: Patients initially developed hypotonia at a mean age of 3.7 months. Mean age at start of nusinersen was 7.3 years; the mean duration of follow-up after starting nusinersen was 46.2 months. At 6-, 18-, 38-, 58-, and 74-month follow-up, the mean changes in CHOP-INTEND scores were 1.0, 2.9, 1.8, 1.5, and 1.5, respectively, and the proportions of patients who showed disease amelioration were 28.6%, 71.4%, 75.0%, 100%, and 100%, respectively. CONCLUSION: Nusinersen is safe and effective in patients with SMA type I, even those with chronic respiratory failure and those on permanent ventilation. No significant adverse effects of nusinersen were observed.

Losartan-Induced Angioedema with Acute Hypoxemic Respiratory Failure (Anaphylaxis): A Case Report.

Angioedema is a condition characterized by swelling of the skin or mucosa resulting from loss of vascular integrity that leads to swelling of mucosal tissues and can lead to life-threatening respiratory compromise. Drug-induced angioedema is not a frequent side effect seen with angiotensin receptor blockers (ARBs), particularly when there are no other contributing risk factors like a prior episode. Few studies reported subsequent angioedema episodes after ARB use in patients who had a prior episode with angiotensin converting enzyme inhibitors; however, there are very few cases that documented non-fatal angioedema after ARB as the only therapy. We report a rare case of life-threatening anaphylaxis after losartan use. We hope that our case will bring awareness to this rare but fatal side effect in order to quickly recognize it and encourage further research.

European Academy of Neurology/Peripheral Nerve Society Guideline on diagnosis and treatment of Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy. Symptoms may vary greatly in presentation and severity. Besides weakness and sensory disturbances, patients may have cranial nerve involvement, respiratory insufficiency, autonomic dysfunction and pain. To develop an evidence-based guideline for the diagnosis and treatment of GBS, using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, a Task Force (TF) of the European Academy of Neurology (EAN) and the Peripheral Nerve Society (PNS) constructed 14 Population/Intervention/Comparison/Outcome questions (PICOs) covering diagnosis, treatment and prognosis of GBS, which guided the literature search. Data were extracted and summarised in GRADE Summaries of Findings (for treatment PICOs) or Evidence Tables (for diagnostic and prognostic PICOs). Statements were prepared according to GRADE Evidence-to-Decision (EtD) frameworks. For the six intervention PICOs, evidence-based recommendations are made. For other PICOs, good practice points (GPPs) are formulated. For diagnosis, the principal GPPs are: GBS is more likely if there is a history of recent diarrhoea or respiratory infection; CSF examination is valuable, particularly when the diagnosis is less certain; electrodiagnostic testing is advised to support the diagnosis; testing for anti-ganglioside antibodies is of limited clinical value in most patients with typical motor-sensory GBS, but anti-GQ1b antibody testing should be considered when Miller Fisher syndrome (MFS) is suspected; nodal-paranodal antibodies should be tested when autoimmune nodopathy is suspected; MRI or ultrasound imaging should be considered in atypical cases; and changing the diagnosis to acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) should be considered if progression continues after 8 weeks from onset, which occurs in around 5% of patients initially diagnosed with GBS. For treatment, the TF recommends intravenous immunoglobulin (IVIg) 0.4 g/kg for 5 days, in patients within 2 weeks (GPP also within 2-4 weeks) after onset of weakness if unable to walk unaided, or a course of plasma exchange (PE) 12-15 L in four to five exchanges over 1-2 weeks, in patients within 4 weeks after onset of weakness if unable to walk unaided. The TF recommends against a second IVIg course in GBS patients with a poor prognosis; recommends against using oral corticosteroids, and weakly recommends against using IV corticosteroids; does not recommend PE followed immediately by IVIg; weakly recommends gabapentinoids, tricyclic antidepressants or carbamazepine for treatment of pain; does not recommend a specific treatment for fatigue. To estimate the prognosis of individual patients, the TF advises using the modified Erasmus GBS outcome score (mEGOS) to assess outcome, and the modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess the risk of requiring artificial ventilation. Based on the PICOs, available literature and additional discussions, we provide flow charts to assist making clinical decisions on diagnosis, treatment and the need for intensive care unit admission.