Early Respiratory Failure Research Articles

Genotype‒phenotype correlation in recessive DNAJB4 myopathy.

Protein aggregate myopathies can result from pathogenic variants in genes encoding protein chaperones. DNAJB4 is a cochaperone belonging to the heat shock protein-40 (HSP40) family and plays a vital role in cellular proteostasis. Recessive loss-of-function variants in DNAJB4 cause myopathy with early respiratory failure and spinal rigidity, presenting from infancy to adulthood. This study investigated the broader clinical and genetic spectrum of DNAJB4 myopathy. In this study, we performed whole-exome sequencing on seven patients with early respiratory failure of unknown genetic etiology. We identified five distinct pathogenic variants in DNAJB4 in five unrelated families of diverse ethnic backgrounds: three loss-of-function variants (c.547C > T, p.R183*; c.775C > T, p.R259*; an exon 2 deletion) and two missense variants (c.105G > C, p.K35N; c.181A > G, p.R61G). All patients were homozygous. Most affected individuals exhibited early respiratory failure, and patients from three families had rigid spine syndrome with axial weakness in proportion to appendicular weakness. Additional symptoms included dysphagia, ankle contractures, scoliosis, neck stiffness, and cardiac dysfunction. Notably, J-domain missense variants were associated with a more severe phenotype, including an earlier age of onset and a higher mortality rate, suggesting a strong genotype‒phenotype correlation. Consistent with a loss of function, the nonsense variants presented decreased stability. In contrast, the missense variants exhibited normal or increased stability but behaved as loss-of-function variants in yeast complementation and TDP-43 disaggregation assays. Our findings suggest that DNAJB4 is an emerging cause of myopathy with rigid spine syndrome of variable age of onset and severity. This diagnosis should be considered in individuals presenting with suggestive symptoms, particularly if they exhibit neck stiffness during infancy or experience respiratory failure in adults without significant limb muscle weakness. Missense variants in the J domain may predict a more severe phenotype.

Genotype-phenotype correlation in recessive DNAJB4 myopathy.

Protein aggregate myopathies can result from pathogenic variants in genes encoding protein chaperones. DNAJB4 is a cochaperone belonging to the heat shock protein-40 (HSP40) family and plays a vital role in cellular proteostasis. Recessive loss-of-function variants in DNAJB4 cause myopathy with early respiratory failure and spinal rigidity, presenting from infancy to adulthood. This study investigated the broader clinical and genetic spectrum of DNAJB4 myopathy. In this study, we performed whole-exome sequencing on seven patients with early respiratory failure of unknown genetic etiology. We identified five distinct pathogenic variants in DNAJB4 in five unrelated families of diverse ethnic backgrounds: three loss-of-function variants (c.547C > T, p.R183*; c.775C > T, p.R259*; an exon 2 deletion) and two missense variants (c.105G > C, p.K35N; c.181A > G, p.R61G). All patients were homozygous. All affected individuals exhibited early respiratory failure, and patients from three families had rigid spine syndrome with axial weakness in proportion to appendicular weakness. Additional symptoms included dysphagia, ankle contractures, scoliosis, neck stiffness, and cardiac dysfunction. Notably, J-domain missense variants were associated with a more severe phenotype, including an earlier age of onset and a higher mortality rate, suggesting a strong genotype-phenotype correlation. Consistent with a loss of function, the nonsense variants presented decreased stability. In contrast, the missense variants exhibited normal or increased stability but behaved as loss-of-function variants in yeast complementation and TDP-43 disaggregation assays. Our findings suggest that DNAJB4 is an emerging cause of myopathy with rigid spine syndrome of variable age of onset and severity. This diagnosis should be considered in individuals presenting with suggestive symptoms, particularly if they exhibit neck stiffness during infancy or experience respiratory failure in adults without significant limb muscle weakness. Missense variants in the J-domain may predict a more severe phenotype.

Severe Varicella-Zoster virus pneumonia in a healthy young adult treated with acyclovir and extracorporeal membrane oxygenation: a case report

Purpose: Varicella-zoster virus (VZV) infection is common in children and is usually benign. In adults VZV infection can present as a severe primary viral pneumonia with acute respiratory failure. VZV infections in adult have a high mortality rate.Case report: A 32-year-old previously healthy male first presented to the emergency department with flulikesymptoms and no rash. Three days later he returned to the emergency department with a disseminatedskin rash and severe acute respiratory distress syndrome that required intubation and mechanical ventilation. A VZV infection was confirmed. Mechanical ventilation was insufficient and venovenous extracorporeal membrane oxygenation was introduced. In addition to supportive measures, he was treated with intravenousacyclovir. During hospitalisation he developed several complications, including severe cor pulmonale necessitating treatment with nitrous oxide and milrinone, disseminated intravascular coagulation necessitating an extracorporeal membrane change, and ventilator-associated pneumonia. He was discharged home in stable condition on hospital day 27.Conclusion: Primary VZV infection in adulthood is associated with several complications. Early recognition ofacute respiratory failure, ventilatory support, and early administration of acyclovir are crucial elements of VZVpneumonia treatment.

Impact of glucose-containing fluid on acute pancreatitis outcomes: A multicenter retrospective analysis

IntroductionFluid resuscitation reduces mortality and morbidity in acute pancreatitis (AP); however, whether glucose-containing fluids negatively impact AP remains uncertain. We aimed to examine the association between glucose-containing fluids and AP outcomes. MethodsThis multicenter retrospective cohort study included patients diagnosed with AP between January 2015 and December 2018. Glucose density was defined as total glucose content divided by total fluid volume (g/dl) on day 1, and was considered high if the level exceeded the median. Endpoints were early organ failure (OF), including cardiovascular, renal, or respiratory system failure within 7 days; 30-day OF; ICU admission; and AP-related 90-day mortality. Logistic regression models, restricted cubic spline curves, and Cox proportional hazards models were used for statistical analysis. ResultsFrom the database, 1,146 patients with AP were included. Early OF occurred in 8.8% of patients within 7 days. The high glucose-density group (>5 g/dl) had increased risk of early OF (9.7% vs. 8.2%; adjusted odds ratio [aOR], 1.69; 95% confidence interval [CI], 1.03–2.80; P = 0.039), respiratory failure (8.0% vs. 6.2%; aOR, 1.88; 95% CI, 1.09–3.24; P = 0.024), cardiovascular failure (3.4% vs. 2.4%; aOR, 3.59; 95% CI, 1.28–10.0; P = 0.015), and ICU admission (6.8% vs. 5.8%; aOR, 2.06; 95% CI, 1.08–3.94; P = 0.029), with a dose-response effect observed for cardiovascular failure and ICU admission. A significant increase 30-day OF risk (adjusted hazard ratio [aHR], 1.70; 95% CI, 1.19–2.45) was also noted. ConclusionExcess glucose-containing fluid was associated with increased risks of overall, respiratory, and cardiovascular OF and ICU admission in AP.

Efficacy of preoperative single-dose dexamethasone in preventing postoperative pulmonary complications following minimally invasive esophagectomy: a retrospective propensity score-matched study

BackgroundThe study was performed to investigate the efficacy and safety of preoperative dexamethasone (DXM) in preventing postoperative pulmonary complications (PPCs) after minimally invasive esophagectomy (MIE).MethodsPatients who underwent total MIE with two-field lymph node dissection from February 2018 to February 2023 were included in this study. Patients who were given either 5 mg or 10 mg DXM as preoperative prophylactic medication before induction of general anesthesia were assigned to the DXM group, while patients who did not receive DXM were assigned to the control group. Preoperative evaluations, intraoperative data, and occurrence of postoperative complications were analyzed. The primary outcome was the incidence of PPCs occurring by day 7 after surgery.ResultsIn total, 659 patients were included in the study; 453 patients received preoperative DXM, while 206 patients did not. Propensity score-matched analysis created a matched cohort of 366 patients, with 183 patients each in the DXM and control groups. A total of 24.6% of patients in the DXM group and 30.6% of patients in the control group had PPCs (P = 0.198). The incidence of respiratory failure was significantly lower in the DXM group than in the control group (1.1% vs 5.5%, P = 0.019). Fewer patients were re-intubated during their hospital stay in the DXM group than in the control group (1.1% vs 5.5%, P = 0.019).ConclusionsPreoperative DXM before induction of anesthesia did not reduce overall PPC development after MIE. Nevertheless, the occurrence of early respiratory failure and the incidence of re-intubation during hospitalization were decreased.Trial registrationChinese Clinical Trial Registry (No. ChiCTR2300071674; Date of registration, 22/05/2023)

Gastric Insufflation with High Flow Nasal Oxygen Therapy in Adult Patients Admitted to Intensive Care Unit: An Observational Study.

With the provision of a small positive end-expiratory pressure (PEEP) effect, high-flow nasal oxygen (HFNO) therapy carries a risk of stomach distension. The present study was conducted to find out the air leak in the gastric antrum leading to gastric distension in adult patients with acute respiratory failure receiving HFNO therapy. Adult patients with early hypoxemic respiratory failure requiring HFNO therapy were enrolled in this trial. Before initiation of HFNO therapy, baseline gastric volume (GV) and the average number of peristaltic contractions over one minute were measured using ultrasound. Once the patient was stabilized on HFNO therapy, a 2nd, 3rd, and 4th ultrasound scans were acquired at 10, 20, and 30 minutes respectively. Vitals and blood gas values were recorded at the baseline and after 30 min of initiation of HFNO therapy. Patient comfort, duration of HFNO therapy, and outcome were also recorded. The GV at 10, 20, and 30 minutes were significantly larger (p < 0.001) compared to baseline. This increase in GV was associated with a significantly increased number of peristaltic contractions and had a significant positive correlation with the HFNO flow (r = 0.541; p < 0.001). The HFNO therapy was well tolerated by most of the patients and led to a significant improvement in the vitals and blood gas parameters at 30 minutes after initiation of HFNO therapy. In adult patients with hypoxemic respiratory failure, the use of HFNO therapy produces gas leaks into the stomach leading to increased gastric volume. The gastric distension increases the peristaltic contraction and higher flows result in more distension. Ramachandran A, Bhatia P, Mohammed S, Kamal M, Chhabra S, Paliwal B. Gastric Insufflation with High Flow Nasal Oxygen Therapy in Adult Patients Admitted to Intensive Care Unit: An Observational Study. Indian J Crit Care Med 2024;28(4):393-398.

Rare Occurrence DNAJB4 Gene Mutation Leads To Early Respiratory Failure In An Indian Neonate

Rare Occurrence DNAJB4 Gene Mutation Leads To Early Respiratory Failure In An Indian Neonate

Calculated Maximal Volume Ventilation (cMVV) as a Marker of Early Respiratory Failure in Amyotrophic Lateral Sclerosis (ALS).

Respiratory failure assessment is among the most debatable research topics in amyotrophic lateral sclerosis (ALS) clinical research due to the wide heterogeneity of its presentation. Among the different pulmonary function tests (PFTs), maximal voluntary ventilation (MVV) has shown potential utility as a diagnostic and monitoring marker, able to capture early respiratory modification in neuromuscular disorders. In the present study, we explored calculated MVV (cMVV) as a prognostic biomarker in a center-based, retrospective ALS population belonging to the Piemonte and Valle d'Aosta registry for ALS (PARALS). A Spearman's correlation analysis with clinical data and PFTs showed a good correlation of cMVV with forced vital capacity (FVC) and a moderate correlation with some other features such as bulbar involvement, ALSFRS-R total score, blood oxygen (pO2), carbonate (HCO3-), and base excess (BE), measured with arterial blood gas analysis. Both the Cox proportional hazard models for survival and the time to non-invasive ventilation (NIV) measurement highlighted that cMVV at diagnosis (considering cMVV(40) ≥ 80) is able to stratify patients across different risk levels for death/tracheostomy and NIV indication, especially considering patients with FVC% ≥ 80. In conclusion, cMVV is a useful marker of early respiratory failure in ALS, and is easily derivable from standard PFTs, especially in asymptomatic ALS patients with normal FVC measures.

Lateral medullary infarction with a large, vertically extending lesion and early onset central respiratory failure

Lateral medullary infarction with a large, vertically extending lesion and early onset central respiratory failure

Structured Light Plethysmography for Non-Invasive Assessment of Respiratory Pattern in Spinal Muscular Atrophy Type 1.

Spinal muscular atrophy (SMA) type 1 is a severe condition leading to early respiratory failure. Treatment options have become available, yet respiratory outcome measures in SMA type 1 are limited. The aim of this study was to assess the respiratory pattern in SMA type 1 patients via structured light plethysmography (SLP). SLP measures the thoraco-abdominal movements by projecting a light grid onto the anterior thoraco-abdominal surface. Cross-sectional study of consecutive children with SMA type 1. All children underwent motor assessment (CHOP-INTEND) and one-minute tidal breathing recording by SLP in supine position while self-ventilating in room air. The Respiratory rate, the abdominal vs. chest contribution to breath (Relative Expired Abdomen%, Relative Expired Chest%) and the severity of thoraco-abdominal paradox (Phase Angle) were acquired. Nineteen patients were included, median (IQR) age 2.3 years (1.4-7.9). Their respiratory pattern captured via SLP showed a raised median (IQR) respiratory rate per age of 33.5 bpm (26.6-41.7), a prevalent abdominal contribution to tidal breathing with median (IQR) Relative Expired Abdomen 77% (68-90) vs. Chest 23% (10-32). Thoracoabdominal paradox was detected (median Phase Angle 48.70°) and its severity correlated negatively with CHOP-INTEND (r -0.8, p < 0.01). SLP captured and quantified the respiratory features of infants and children with SMA type 1.

Noninvasive Assessment of Impaired Gas Exchange with the Alveolar Gas Monitor Predicts Clinical Deterioration in COVID-19 Patients.

The COVID-19 pandemic magnified the importance of gas exchange abnormalities in early respiratory failure. Pulse oximetry (SpO2) has not been universally effective for clinical decision-making, possibly because of limitations. The alveolar gas monitor (AGM100) adds exhaled gas tensions to SpO2 to calculate the oxygen deficit (OD). The OD parallels the alveolar-to-arterial oxygen difference (AaDO2) in outpatients with cardiopulmonary disease. We hypothesized that the OD would discriminate between COVID-19 patients who require hospital admission and those who are discharged home, as well as predict need for supplemental oxygen during the index hospitalization. Patients presenting with dyspnea and COVID-19 were enrolled with informed consent and had OD measured using the AGM100. The OD was then compared between admitted and discharged patients and between patients who required supplemental oxygen and those who did not. The OD was also compared to SpO2 for each of these outcomes using receiver operating characteristic (ROC) curves. Thirty patients were COVID-19 positive and had complete AGM100 data. The mean OD was significantly (p = 0.025) higher among those admitted 50.0 ± 20.6 (mean ± SD) vs. discharged 27.0 ± 14.3 (mean ± SD). The OD was also significantly (p < 0.0001) higher among those requiring supplemental oxygen 60.1 ± 12.9 (mean ± SD) vs. those remaining on room air 25.2 ± 11.9 (mean ± SD). ROC curves for the OD demonstrated very good and excellent sensitivity for predicting hospital admission and supplemental oxygen administration, respectively. The OD performed better than an SpO2 threshold of <94%. The AGM100 is a novel, noninvasive way of measuring impaired gas exchange for clinically important endpoints in COVID-19.

Practices and Outcomes from a Prospective, Multicenter Registry for Preterm Newborns with Pulmonary Hypertension

To describe current treatment practices of preterm infants with early hypoxemic respiratory failure (HRF) and pulmonary hypertension (PH) and their association with patient outcomes. We developed a prospective, observational, multicenter clinical registry of preterm newborns <34weeks' gestation with HRF and PH, based on either clinical or echocardiographic evidence during the first 72hours of life, from 28 neonatal intensive care units in the US from 2017 through 2022. The primary end point was mortality among those who did or did not receive PH-targeted treatment, and the secondary end points included comparisons of major morbidities. Variables were compared using t tests, Wilcoxon rank-sum tests, Fisher exact tests, and χ² tests. We analyzed the results of 224 preterm infants enrolled in the registry. Of which, 84% (188/224) received PH-targeted treatment, most commonly inhaled nitric oxide (iNO). Early mortality in this cohort was high, as 33% (71/224) of this sample died in the first month of life, and 77% of survivors (105/137) developed bronchopulmonary dysplasia. Infants who received PH-targeted treatment had higher oxygenation indices at the time of enrollment (28.16 [IQR: 13.94, 42.5] vs 15.46 [IQR: 11.94, 26.15]; P=.0064). Patient outcomes did not differ between those who did or did not receive PH-targeted therapy. Early-onset HRF with PH in preterm infants is associated with a high early mortality and a high risk of developing bronchopulmonary dysplasia. iNO is commonly used to treat early-onset PH in preterm infants with HRF. In comparison with untreated infants with lower oxygenation indices, iNO treatment in severe PH may prevent poorer outcomes.

Exome sequencing links the SUMO protease SENP7 with fatal arthrogryposis multiplex congenita, early respiratory failure and neutropenia

BackgroundSUMOylation involves the attachment of small ubiquitin-like modifier (SUMO) proteins to specific lysine residues on thousands of substrates with target-specific effects on protein function. Sentrin-specific proteases (SENPs) are proteins involved...

Enhancing Total Optical Throughput of Microscopy with Deep Learning for Intravital Observation.

The significance of performing large-depth dynamic microscopic imaging in vivo for life science research cannot be overstated. However, the optical throughput of the microscope limits the available information per unit of time, i.e., it is difficult to obtain both high spatial and temporal resolution at once. Here, a method is proposed to construct a kind of intravital microscopy with high optical throughput, by making near-infrared-II (NIR-II, 900-1880nm) wide-field fluorescence microscopy learn from two-photon fluorescence microscopy based on a scale-recurrent network. Using this upgraded NIR-II fluorescence microscope, vessels in the opaque brain of a rodent are reconstructed three-dimensionally. Five-fold axial and thirteen-fold lateral resolution improvements are achieved without sacrificing temporal resolution and light utilization. Also, tiny cerebral vessel dilatations in early acute respiratory failure mice are observed, with this high optical throughput NIR-II microscope at an imaging speed of 30fps.

Clinical-pathological features and muscle imaging findings in 36 Chinese patients with rimmed vacuolar myopathies: case series study and review of literature.

Rimmed vacuolar myopathies (RVMs) are a group of genetically heterogeneous diseases that share histopathological characteristics on muscle biopsy, including the aberrant accumulation of autophagic vacuoles. However, the presence of non-coding sequences and structural mutations, some of which remain undetectable, confound the identification of pathogenic mutations responsible for RVMs. Therefore, we assessed the clinical profiles and muscle magnetic resonance imaging (MRI) changes in 36 Chinese patients with RVMs, emphasizing the role of muscle MRI in disease identification and differential diagnosis to propose a comprehensive literature-based imaging pattern to facilitate improved diagnostic workup. All patients presented with rimmed vacuoles with varying degrees of muscular dystrophic changes and underwent a comprehensive evaluation using clinical, morphological, muscle MRI and molecular genetic analysis. We assessed muscle changes in the Chinese RVMs and provided an overview of the RVMs, focusing on the patterns of muscle involvement on MRI. A total of 36 patients, including 24 with confirmed distal myopathy and 12 with limb-girdle phenotype, had autophagic vacuoles with RVMs. Hierarchical clustering of patients according to the predominant effect of the distal or proximal lower limbs revealed that most patients with RVMs could be distinguished. GNE myopathy was the most prevalent form of RVMs observed in this study. Moreover, MRI helped identify the causative genes in some diseases (e.g., desminopathy and hereditary myopathy with early respiratory failure) and confirmed the pathogenicity of a novel mutation (e.g., adult-onset proximal rimmed vacuolar titinopathy) detected using next-generation sequencing. Collectively, our findings expand our knowledge of the genetic spectrum of RVMs in China and suggest that muscle imaging should be an integral part of assisting genetic testing and avoiding misdiagnosis in the diagnostic workup of RVM.

5599228 PITFALLS IN DIAGNOSING THROMBOTIC THROMBOCYTOPENIC PURPURA IN SICKLE CELL DISEASE

Background: Thrombotic microangiopathies are diagnosed by thrombocytopenia, microangiopathic haemolytic anaemia and evidence of end organ damage. In TTP this includes neurological symptoms, renal impairment and cardiac microthrombi. Confirmation of the diagnosis is severe deficiency (<10%) of the metalloproteinase ADAMTS13 and/or the presence of an inhibitor. The diagnosis of TTP in sickle cell disease (SCD) can be challenging as SCD is characterised by a chronic state of haemolysis often with very abnormal peripheral blood morphology so clinical features suggestive of TTP can be due to complications of SCD. More specifically, the coexistence of neurological impairment and thrombocytopenia seen in fat embolism syndrome (FES) complicating SCD can lead to an erroneous diagnosis of TTP. FES typically affects non-homozygous patients and those with a previously mild course of their illness manifesting with respiratory failure, neurological signs, thrombocytopenia and potential involvement of any system leading to high morbidity and mortality. Peripheral blood morphology typically shows very high number of nucleated red blood cells (nRBC). Aims: To identify published cases of TTP in patients with SCD and review the diagnostic approach. Methods: A PubMed literature search was performed using the terms “sickle cell” and “thrombotic thrombocytopenic purpura”/”TTP”. Results: Of 19 cases identified, 9 were individual case reports and a case series of 10. All patients had very mild course of their SCD. The median nadir platelet count was 38 x 109/L (7-70). 84% had neurological involvement either at presentation or shortly afterwards; primarily altered sensorium/drop in GCS. 79% patients also had severe type I respiratory failure either preceding or occurring simultaneously with the development of neurological signs and associated with extensive changes on chest imaging. Schistocytes were identified in all cases but in the vast majority at relatively low levels; at the same time, all showed large numbers of nRBCs. 18 of the 19 cases were published after 1998; in 15 there was no mention of ADAMTS13 testing at all. In the 3 cases with ADAMTS13 levels, all were normal; 2 samples were obtained before therapeutic plasma exchange (TPE) and 1 after. 18 patients received TPE and 1 an infusion of donor plasma. However, prior to TPE, all patients had already received red cell transfusion achieving Hb S levels of 30% or less. There were 2 (11%) deaths while the remainder of patients achieved complete recovery. One due to intracranial haemorrhage and the other, sepsis in the context of immunosuppression for prevention of TTP recurrence. The presence of early respiratory failure, the inconclusive morphological findings, the degree of thrombocytopenia, and the complete absence of confirmatory ADAMTS13 results bring the diagnosis of TTP to question in all cases. Given the clinical presentations, we suspect that some of these patients had FES. The positive outcomes may be explained by the fact that all patients received adequate red cell transfusion, but also the possible beneficial effect of TPE in acute complications of SCD with a hyper inflammatory component such as FES. Conclusion: The diagnosis of TTP in patients with SCD is challenging due to many overlapping features. It should not be made without confirmatory ADAMTS13 results and the possibility of alternative diagnoses should be explored.

Hereditary myopathy with early respiratory failure: case report

BackgroundHereditary myopathy with early respiratory failure (HMERF) is a rare myopathy that affects respiratory muscles in the early course of the disease leading to respiratory insufficiency. It is caused by mutation in titin (TTN) gene.Case reportAt the age of 29, our female patient presented with a slowly progressive proximal lower limb and axial muscle weakness and respiratory issues. Her late mother had similar problems, she died at a young age and was never properly diagnosed. Patient’s creatine kinase level was elevated up to three times above the upper limit of normal. Whole exome sequencing showed a pathogenic variant c.95372G>A in the TTN gene leading to the final diagnosis of HMERF. Cardiac examination was normal. Patient started to use a non-invasive nocturnal ventilation at age of 35.ConclusionsOur case is the first described case of HMERF in Serbian population. Multidisciplinary neurological and pulmonary approach is of great importance in HMERF and similar diseases. This case highlights the importance of considering early neuromuscular respiratory insufficiency as a distinctive syndrome leading to a challenging and broad differential diagnosis.

Case Report: Recurrence of Acute Respiratory Distress Syndrome After Bilateral Lung Transplantation

The main causes of early respiratory failure after lung transplantation include primary graft dysfunction (PGD), acute rejection, and infection. This report describes a case of unclear early respiratory failure after bilateral lung transplantation for extensive COVID-19-induced acute respiratory distress syndrome (ARDS). We reviewed the patient file to investigate the course of the functional decline and evaluate reasons for early graft failure. Analyzed data included crossmatching results, biopsy results, HLA antibodies testing, bronchoalveolar lavages, respiratory parameters, and medications. After an initial excellent early postoperative course, the patient developed progressive respiratory failure, making re-implantation of extracorporeal membrane oxygenation (ECMO) support necessary. An extensive diagnostic workup revealed no signs of infection or rejection. Because the patient showed no signs of improvement with any treatment, lung-protective ventilation with the intermittent prone position was initiated. The patient's respiratory situation and bilateral opacities slowly improved over the next few weeks, and ECMO support was eventually discontinued. With no evidence of PGD, rejection, or infection, recurrent ARDS caused by a systemic immunologic process was seen as the only plausible cause for the patient's respiratory failure after lung transplantation. The fact that ARDS can develop extrapulmonarily, without direct viral or bacterial damage, makes us conclude that the preceding systemic activation and recruitment of immune cells by the primarily injured lung could potentially lead to the recurrence of ARDS even if the injured organ is removed.

Efficacy of maintaining low-tidal volume mechanical ventilation as compared to resting lung strategy during coronary artery bypass graft cardiopulmonary bypass surgery: A post-hoc analysis of the MECANO trial

Study objectiveTo compare a low-tidal-volume with positive end-expiratory pressure strategy (VENT strategy) to a resting-lung-strategy (i.e., no-ventilation (noV) strategy) during cardiopulmonary bypass for coronary artery bypass graft surgery on the incidence of postoperative pulmonary complications. DesignPost-hoc analysis of the MECANO trial which was a prospective single-center, blind, randomized, parallel-group controlled trial. SettingTertiary care cardiac surgery center. PatientsPatients who underwent isolated on-pump coronary bypass surgery were randomized either to VENT or noV group. InterventionDuring the cardiopulmonary bypass phase of the cardiac surgery procedure, mechanical ventilation in the VENT group consisted of a tidal volume of 3 mL/kg, a respiratory rate of 5 per minute and a positive end-expiratory pressure of 5 cmH2O. Patients in the noV group received no ventilation during this phase. MeasurementsPrimary composite outcome combining death, early respiratory failure, ventilation support beyond day 2 and reintubation. Main resultsIn this post-hoc analysis, we retained 725 patients who underwent isolated CABG surgery, from the 1501 patients included in the original study. There were 352 in the VENT group and 373 patients in the noV group. Post-hoc comparison yielded no differences in baseline characteristics between these two groups. The primary outcome occurred less frequently in the VENT group than in the noV group, with 44 (12.5%) and 76 (20.4%) respectively (odds-ratio (OR) = 0.56 (0.37–0.84), p = 0.004). There were fewer early respiratory dysfunctions and prolonged respiratory support in the VENT group (respectively, OR = 0.34 (0.12–0.96) p = 0.033 and OR = 0.51 (0.27–0.94) p = 0.029). Complications related to mechanical ventilation were similar in the two groups. ConclusionsIn this post-hoc analysis, maintaining low-tidal ventilation compared to a resting-lung strategy was associated with fewer pulmonary postoperative complications in patients who underwent isolated CABG procedures.

Novel mutations in RSPH4A and TTN genes lead to primary ciliary dyskinesia-hereditary myopathy with early respiratory failure overlap syndrome

Novel mutations in RSPH4A and TTN genes lead to primary ciliary dyskinesia-hereditary myopathy with early respiratory failure overlap syndrome