Fatal Respiratory Failure Research Articles

Genetic Panel Reveals Coexisting Neuromuscular Disorders in Patients With Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy is a genetically based neuromuscular disorder characterized by progressive physical impairment and cardiomyopathy in children, leading to fatal cardiac or respiratory failure. Duchenne muscular dystrophy shares some overlapping clinical features with other disorders, complicating clinical differentiation. We hypothesized that some Duchenne muscular dystrophy patients may have a secondary neuromuscular disorders that could negatively skew data during pharmaceutical clinical trials and lead to incomplete treatment plans. Consecutive genetic panels on 353 patients were reviewed. Thirty-two (32; 9.1%) patients with Duchenne muscular dystrophy were identified. Three (3; 9.4%) were found to have at least 1 genetically confirmed secondary neuromuscular disorder. Overlooking these coexisting disorders could lead to unexpected treatment failures, potentially affecting medication efficacy in trials or commercial use. Secondary neuromuscular disorders should be considered in Duchenne muscular dystrophy patients before clinical trial enrollment or treatment planning, with expanded genetic testing, such as whole exome sequencing or whole genome sequencing, likely to reveal even more secondary disorders.

Non-emergent hemoptysis in patients with primary or metastatic lung tumors: The role of transarterial embolization

PurposeTo evaluate the role of systemic arterial embolization for the management of non-emergent hemoptysis in patients with primary or metastatic lung tumors. Materials and methodsThis is a retrospective single center study of consecutive patients who underwent systemic arterial embolization for non-emergent hemoptysis between 2011 and 2023. Study endpoints included technical success, clinical success (partial or complete resolution of hemoptysis) and overall survival. Hemoptysis-free and overall survival were estimated using the Kaplan-Meier method. Predictive factors for hemoptysis-free survival and overall survival were evaluated using univariate analysis (Cox regression). Post-procedural 30-day adverse events were recorded in line with Common Terminology Criteria for Adverse Events (CTCAE) v5.0. ResultsA total of 30 patients were identified. Technical success was achieved in 24/30 (80 %) patients. Clinical success following embolization was achieved in 23/30 (76.7 %) patients. Median length of hospitalization was 5 days (Range: 1 to 16 days). Median overall survival was 194 days (95 % CI: 89 to 258). Median hemoptysis-free survival was 286 days (95 % CI: 42 to not reached). No significant clinical or procedural predictors of hemoptysis-free survival or overall survival were identified. Serious adverse events (CTCAE Grade > 3) occurred in 1 patient (3.4 % − fatal respiratory failure). ConclusionEmbolization of non-emergent hemoptysis in patients with lung malignancies is safe and effective. Recurrence is however high in this patient population, likely due to the nature of the underlying disease.

Procoagulant phenotype of virus-infected pericytes is associated with portal thrombosis and intrapulmonary vascular dilations in fatal COVID-19

The underlying mechanisms and clinical impact of portal microthrombosis in severe COVID-19 are unknown. Intrapulmonary vascular dilation (IPVD)-related hypoxia has been described in severe liver diseases. We hypothesised that portal microthrombosis is associated with IPVD and fatal respiratory failure in COVID-19. Ninety-three patients who died from COVID-19 were analysed for portal microvascular damage (histology), IPVD (histology and chest-computed tomography, CT), and hypoxemia (arterial blood gas). Seventeen patients who died from COVID-19-unrelated pneumonia served as controls. Vascular lesions and microthrombi were phenotyped for endothelial (vWF) and pericyte (αSMA/PDGFR-β) markers, tissue factor (TF), viral spike protein and nucleoprotein (SP, NP), fibrinogen, and platelets (CD41a). Viral particles in vascular cells were assessed by transmission electron microscopy. Cultured pericytes were infected with SARS-CoV-2 to measure TF expression and tubulisation of human pulmonary microvascular endothelial cells was assessed upon vWF treatment. IPVD was present in 16/66 patients with COVID-19, with available liver and lung histology, and was associated with younger age (62 vs. 78 years-old), longer illness (25 vs. 14 days), worsening hypoxemia (PaO2/FiO2 from 209 to 89), and an increased requirement for ventilatory support (63% vs. 22%) compared to COVID-19/Non-IPVD. IPVD, absent in controls, was confirmed by chest CT. COVID-19/IPVD liver histology showed portal microthrombosis in >82.5% of portal areas, with a thicker wall of αSMA/PDGFR-β+/SP+/NP+ pericytes compared with COVID-19/Non-IPVD. Thrombosed portal venules correlated with αSMA+ area, whereas infected SP+/NP+ pericytes expressed TF. SARS-CoV-2 viral particles were observed in portal pericytes. Invitro SARS-CoV-2 infection of pericytes upregulated TF and induced endothelial cells to overexpress vWF, which expanded human pulmonary microvascular endothelial cell tubules. SARS-CoV-2 infection of liver pericytes elicits a local procoagulant response associated with extensive portal microthrombosis, IPVD and worsening respiratory failure in fatal COVID-19. Vascular involvement of the liver represents a serious complication of COVID-19 infection that must be considered in the work-up of patients with long-lasting and progressively worsening respiratory failure, as it may associate with the development of intrapulmonary vascular dilations. This clinical picture is associated with a procoagulant phenotype of portal venule pericytes, which is induced by SARS-CoV-2 infection of pericytes. Both observations provide a model that may apply, at least in part, to other vascular disorders of the liver, featuring obliterative portal venopathy, similarly characterised at the clinical level by development of hypoxemia and at the histological level by phlebosclerosis and reduced calibre of the portal vein branches in the absence of cirrhosis. Moreover, our findings shed light on an overlooked player in the pathophysiology of thrombosis, i.e. pericytes, which may present a novel therapeutic target.

E-cigarettes, e-liquids and drug vaping – forensic perspectives on electronic nicotine delivery systems

Electronic cigarettes are devices that produce an aerosol by heating e-liquid. Their history can be traced back to the 20th century but their popularity exponentially increased in the 21st century. Multiple generations and types of e-cigarettes are available on the market with an astounding choice of e-liquids. They gained popularity in almost all countries and among all age groups. The regulation concerning them varies drastically across the world. The health impact is still not fully understood. Although e-cigarettes contain less toxic substances compared to regular cigarettes their use is still not harmless. Some studies suggest a correlation between e-cigarettes and cardiovascular diseases and a potential cancer risk. However, the most noticeable is the effect on the respiratory system. There have been reported cases of fatal respiratory failure caused by e-cigarette use. There has been an increased interest in using e-cigarettes for recreational drug use, notably cannabinoids. E-liquids have been used in suicide attempts. They are usually ingested causing potentially lethal poisoning. Furthermore, lung biopsy and extensive medical history analysis should be the cornerstone of forensic examination of deaths involving e-cigarettes.

Cellular therapies for idiopathic pulmonary fibrosis: current progress and future prospects.

Idiopathic pulmonary fibrosis (IPF) is an interstitial, fibrotic lung disease characterized by progressive damage. Lung tissues with IPF are replaced by fibrotic tissues with increased collagen deposition, modified extracellular matrix, all which overall damages the alveoli. These changes eventually impede the gas exchange function of the alveoli, and eventually leads to fatal respiratory failure of the lung. Investigations have been conducted to further understand IPF's pathogenesis, and significant progress in understanding its development has been made. Additionally, two therapeutic treatments, Nintedanib and Pirfenidone, have been approved and are currently used in medical applications. Moreover, cell-based treatments have recently come to the forefront of developing disease therapeutics and are the focus of many current studies. Furthermore, a sizable body of research encompassing basic, pre-clinical, and even clinical trials have all been amassed in recent years and hold a great potential for more widespread applications in patient care. Herein, this article reviews the progress in understanding the pathogenesis and pathophysiology of IPF. Additionally, different cell types used in IPF therapy were reviewed, including alveolar epithelial cells (AECs), circulating endothelial progenitors (EPCs), mixed lung epithelial cells, different types of stem cells, and endogenous lung tissue-specific stem cells. Finally, we discussed the contemporary trials that employ or explore cell-based therapy for IPF.

A promoterless AAV6.2FF-based lung gene editing platform for the correction of surfactant protein B deficiency

Surfactant protein B (SP-B) deficiency is a rare genetic disease that causes fatal respiratory failure within the first year of life. Currently, the only corrective treatment is lung transplantation. Here, we co-transduced the murine lung with adeno-associated virus 6.2FF (AAV6.2FF) vectors encoding a SaCas9-guide RNA nuclease or donor template to mediate insertion of promoterless reporter genes or the (murine) Sftpb gene in frame with the endogenous surfactant protein C (SP-C) gene, without disrupting SP-C expression. Intranasal administration of 3×1011 vg donor template and 1×1011 vg nuclease consistently edited approximately 6% of lung epithelial cells. Frequency of gene insertion increased in a dose-dependent manner, reaching 20%-25% editing efficiency with the highest donor template and nuclease doses tested. We next evaluated whether this promoterless gene editing platform could extend survival in the conditional SP-B knockout mouse model. Administration of 1×1012 vg SP-B-donor template and 5×1011 vg nuclease significantly extended median survival (p= 0.0034) from 5days in the untreated off doxycycline group to 16days in the donor AAV and nuclease group, with one gene-edited mouse living 243days off doxycycline. This AAV6.2FF-based gene editing platform has the potential to correct SP-B deficiency, as well as other disorders of alveolar type II cells.

Surfactant Metabolism Dysfunction Type 3 (SMDP3)

Surfactant (surface-active-agent) is a compound of phospholipids and proteins which are synthesized and secreted into the alveolus by type II epithelial cells, where it functions to decrease surface tension, maintaining alveolar expansion, to facilitate pulmonary compliance. Surfactant proteins (SP)A, B, C, D represent around 8% of total components, but has vital role in optimizing rapid adsorption and spreading of phospholipids. ATP-binding cassette sub-family A member 3, protein that encoded by ABCA3 gene, which located in human chromosome 16p13.3, is synthesized in endoplasmic reticulum and migrated to lysosomal-derived organelles of alveolar type II cells, formally known as lamellar bodies. Once accumulate into the membrane, ABCA3 can directed surfactant phospholipid into the lumen of lamellar bodies and create tight packed of surfactant lipids and proteins. Mutation of the ATP-binding cassette transporter gene ABCA3 cause failure in lamellar body synthesis and result in decreased production of surfactant, along with respiratory distress syndrome, and fatal respiratory failure.

The RESISTANT study (Respiratory Muscle Training in Patients with Spinal Muscular Atrophy): study protocol for a randomized controlled trial

BackgroundSpinal Muscular Atrophy (SMA) is characterized by progressive and predominantly proximal and axial muscle atrophy and weakness. Respiratory muscle weakness results in impaired cough with recurrent respiratory tract infections, nocturnal hypoventilation, and may ultimately lead to fatal respiratory failure in the most severely affected patients. Treatment strategies to either slow down the decline or improve respiratory muscle function are wanting.ObjectiveThe aim of this study is to assess the feasibility and efficacy of respiratory muscle training (RMT) in patients with SMA and respiratory muscle weakness.MethodsThe effect of RMT in patients with SMA, aged ≥ 8 years with respiratory muscle weakness (maximum inspiratory mouth pressure [PImax] ≤ 80 Centimeters of Water Column [cmH2O]), will be investigated with a single blinded randomized sham-controlled trial consisting of a 4-month training period followed by an 8-month open label extension phase.InterventionThe RMT program will consist of a home-based, individualized training program involving 30-breathing cycles through an inspiratory and expiratory muscle training device. Patients will be instructed to perform 10 training sessions over 5–7 days per week. In the active training group, the inspiratory and expiratory threshold will be adjusted to perceived exertion (measured on a Borg scale). The sham-control group will initially receive RMT at the same frequency but against a constant, non-therapeutic resistance. After four months the sham-control group will undergo the same intervention as the active training group (i.e., delayed intervention). Individual adherence to the RMT protocol will be reviewed every two weeks by telephone/video call with a physiotherapist.Main study parameters/endpointsWe hypothesize that the RMT program will be feasible (good adherence and good acceptability) and improve inspiratory muscle strength (primary outcome measure) and expiratory muscle strength (key secondary outcome measure) as well as lung function, patient reported breathing difficulties, respiratory infections, and health related quality of life (additional secondary outcome measures, respectively) in patients with SMA.DiscussionRMT is expected to have positive effects on respiratory muscle strength in patients with SMA. Integrating RMT with recently introduced genetic therapies for SMA may improve respiratory muscle strength in this patient population.Trial registrationRetrospectively registered at clinicaltrial.gov: NCT05632666.

First Drug for Treating Hepatorenal Syndrome.

Terlipressin (Terlivaz) has been approved as the first drug to treat hepatorenal syndrome.The drug may cause serious or fatal respiratory failure. Nurses should confirm that patients have an oxygen saturation level by pulse oximetry of at least 90% in order to start therapy.

MiR-146a, miR-221, and miR-155 are Involved in Inflammatory Immune Response in Severe COVID-19 Patients

COVID-19 infection triggered a global public health crisis during the 2020-2022 period, and it is still evolving. This highly transmissible respiratory disease can cause mild symptoms up to severe pneumonia with potentially fatal respiratory failure. In this cross-sectional study, 41 PCR-positive patients for SARS-CoV-2 and 42 healthy controls were recruited during the first wave of the pandemic in Mexico. The plasmatic expression of five circulating miRNAs involved in inflammatory and pathological host immune responses was assessed using RT-qPCR (Reverse Transcription quantitative Polymerase Chain Reaction). Compared with controls, a significant upregulation of miR-146a, miR-155, and miR-221 was observed; miR-146a had a positive correlation with absolute neutrophil count and levels of brain natriuretic propeptide (proBNP), and miR-221 had a positive correlation with ferritin and a negative correlation with total cholesterol. We found here that CDKN1B gen is a shared target of miR-146a, miR-221-3p, and miR-155-5p, paving the way for therapeutic interventions in severe COVID-19 patients. The ROC curve built with adjusted variables (miR-146a, miR-221-3p, miR-155-5p, age, and male sex) to differentiate individuals with severe COVID-19 showed an AUC of 0.95. The dysregulation of circulating miRNAs provides new insights into the underlying immunological mechanisms, and their possible use as biomarkers to discriminate against patients with severe COVID-19. Functional analysis showed that most enriched pathways were significantly associated with processes related to cell proliferation and immune responses (innate and adaptive). Twelve of the predicted gene targets have been validated in plasma/serum, reflecting their potential use as predictive prognosis biomarkers.

A Fatal Case of Metastatic Pulmonary Calcification during the Puerperium

We present an unusual case of a fatal respiratory failure in a young woman developed two weeks after she gave birth at home. Circumstantial and clinical features of the case were strongly suggestive for a 'classical' septic origin of the respiratory symptoms. Autopsy, together with histopathological and immunohistochemical analyses allowed demonstrating a massive calcium redistribution consisting of an important osteolysis, especially from cranial bones and abnormal accumulation in lungs and other organs. Such physiopathology was driven by a primary hyperparathyroidism secondary to a parathyroid carcinoma as demonstrated by immunohistochemistry. This very rare case is furthermore characterised by a regular pregnancy course, ended with the birth of a healthy new-born. A complex interaction between pregnancy physiology and hyperparathyroidism might be hypothesised, determining the discrepancy between the relative long period of wellness and the tumultuous cascade occurred in the puerperium.

Oral Mucosal Sparing in High-Dose Total Body Irradiation (TBI) prior to Stem Cell Transplantation (SCT) for Acute Leukemia

<h3>Purpose/Objective(s)</h3> High-dose TBI prior to SCT for acute leukemia has been previously associated with superior leukemic control at the expense of non-relapse mortality (NRM). High-grade oral mucositis (OM) may contribute to NRM. We hypothesized that oral mucosal sparing (OMS) TBI delivered with intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) might reduce NRM due to acute OM (occurring within 30 days). <h3>Materials/Methods</h3> Patients treated with high dose, IMRT/VMAT-based TBI prior to SCT for acute lymphocytic leukemia (ALL) or myeloid leukemia (AML) at our institution between 09/2020 and 02/2022 were retrospectively identified. TBI was prescribed to 13.2 or 12 Gy, given in 8 twice daily fractions at least 6 hours apart. The planning target volume (PTV) was defined as the entire body minus organs at risk including the heart, lungs, kidneys, and breasts. After the first 15 patients, we adopted the OMS technique in which the mucosal surfaces of the oral cavity and oropharynx were excluded from the PTV and limited to mean dose < 7 Gy. Fisher's exact tests were used to compare proportions between groups and T-tests were used to compare means between groups. Toxicity was graded according to CTCAEv5. <h3>Results</h3> 25 patients met inclusion criteria. Median patient age was 28 years (range 18-65). 18 patients (72%) had B-ALL, 6 (24%) had T-ALL, and 1 (4%) had AML. Conditioning chemotherapy was cyclophosphamide (n=5, 20%), etoposide (n=9, 36%), or fludarabine (n=11, 44%). Graft vs host disease (GVHD) prophylaxis was mycophenolate mofetil, cyclophosphamide, and tacrolimus (n=12, 48%) or tacrolimus and methotrexate (n=13, 52%). The mean oral mucosal dose was 6.6 Gy vs 13.9 Gy for sparing vs non-sparing, respectively (p < 0.0001). Highest grade OM was 0 (n=7, 28%), 1 (n=1, 4%), 2 (n=3, 12%), 3 (n=11, 44%), or 5 (n=3, 12%). Median time to grade ≥3 OM was 8.5 days (range 0-15) after SCT. Four patients had NRM, including one case of fatal GVHD, and three due to severe OM leading to aspiration pneumonia and fatal respiratory failure (days +4, +5, +8). All three NRM due to OM occurred in patients treated before OMS was instituted (3 of 15 patients, 20%). While no cases of NRM due to OM occurred in patients treated with OMS, the difference was not statistically significant (p = 0.2). Likewise, there was no difference in risk of any OM (90% vs 60%, p=0.2) or grade ≥3 OM (60% vs 53%, p = 0.8) for sparing vs non-sparing, respectively. There was a non-significant trend towards decreased NRM from OM in patients receiving fludarabine (0 of 11) vs etoposide (1 of 9, 11%) or cyclophosphamide (2 of 5, 40%) (p = 0.08), though 91% of patients who received fludarabine also received mucosal sparing. There was no difference in NRM due to OM by GVHD prophylactic regimen (p = 0.5). <h3>Conclusion</h3> The etiology of acute OM following TBI for acute leukemia is multifactorial. Though limited by sample size, these results suggest exclusion of the oral mucosa from TBI with IMRT/VMAT effectively reduces dose to the oral mucosa and may decrease risk of NRM from OM.

4D flow MRIで肺葉切除術後の急性期に肺動脈本幹に渦流を認めた1例：致死的呼吸不全の予兆であった可能性

4D flow MRIで肺葉切除術後の急性期に肺動脈本幹に渦流を認めた1例：致死的呼吸不全の予兆であった可能性

Prognostic value of neutrophils to lymphocytes and platelets ratio for 28-day mortality in patients with acute respiratory distress syndrome: a retrospective study

BackgroundAcute respiratory distress syndrome (ARDS) is a rapidly progressive and fatal respiratory failure disease that often occurs in critically ill patients. Since ARDS is associated with immune dysregulation and coagulation abnormalities, it is necessary to identify an appropriate predictor that can accurately predict ARDS mortality based on its pathophysiology. Therefore, this study aimed to evaluate the clinical value of neutrophils to lymphocytes and platelets ratio (N/LPR) in predicting 28-day mortality in ARDS patients.MethodsFrom July 2018 to October 2021, the medical records of ARDS patients were retrospective reviewed. Neutrophil count, lymphocyte count, and platelet count were collected, and the neutrophil-to-lymphocyte ratio (NLR) and N/LPR were calculated. Multivariate logistic regression analyses were performed to identify independent predictors of 28-day mortality in ARDS. Receiver operating characteristic (ROC) curve with the area under curve (AUC) was used to evaluate optimal cut-off values for 28-day mortality in ARDS. Kaplan–Meier analysis was used to estimate the 28-day survival probabilities stratified by optimal cut-off values of N/LPR and NLR.ResultsA total of 136 ARDS patients were included in this study and were further divided into survivors (n = 69) and non-survivors (n = 67) groups according to their survival status on day 28. There were no significant differences between the two groups in age, sex, history of smoking and drinking, comorbidities, and reasons of admission (P > 0.05). Non-survivors had significantly higher neutrophil counts, NLR and N/LPR and had significantly lower platelet counts than survivors (P < 0.05). Multivariate regression analysis revealed that N/LPR, NLR and platelet counts were independent predictors for 28-day mortality in ARDS (P < 0.05). The ROC analyses showed that N/LPR with optimal cut-off value of 10.57 (sensitivity: 74.6%; specificity: 72.5%) is a more reliable predictor for 28-day mortality in ARDS than NLR and platelet count (AUC: 0.785 vs. 0.679 vs. 0.326). Further subgroup analysis confirmed that ARDS patients with N/LPR < 10.57 had significantly lower 28-day mortality than patients with N/LPR ≥ 10.57 (P < 0.001). Kaplan–Meier analysis also confirmed that ARDS patients with N/LPR < 10.57 had significantly longer survival.ConclusionN/LPR is an independent risk factor associated with 28-day mortality in ARDS patients and shows better performance in predicting mortality rate than NLR.

Correlating SFTPC gene variants to interstitial lung disease in Egyptian children

BackgroundInterstitial lung disease (ILD) is a broad heterogeneous group of lung disorders that is characterized by inflammation of the lungs. Surfactant dysfunction disorders are a rare form of ILD diseases that result from mutations in surfactant protein C gene (SFTPC) with prevalence of approximately 1/1.7 million births. SFTPC patients are presented with clinical manifestations of ILD ranging from fatal respiratory failure of newborn to chronic respiratory problems in children. In the current study, we aimed to investigate the spectrum of SFTPC genetic variants as well as the correlation of the SFTPC gene mutations with ILD disease in twenty unrelated Egyptian children with diffuse lung disease and suspected surfactant dysfunction using Sanger sequencing. ResultsSequencing of SFTPC gene revealed five variants: c.42+35G>A (IVS1+35G>A) (rs8192340) and c.43-21T>C (IVS1-21T>C) (rs13248346) in intron 1, c.436-8C>G (IVS4-8C>G) (rs2070687) in intron 4, c.413C>A p.T138N (rs4715) in exon 4, and c.557G>Ap.S186N (rs1124) in exon 5. ConclusionThe present study confirms the association of detecting variants of SFTPC with surfactant dysfunction disorders.

Phase I study of autologous T cells bearing fully-humanized chimeric antigen receptors targeting mesothelin in mesothelin- expressing cancers (314)

<b>Objectives:</b> In previous clinical studies using a murine-derived CAR construct targeted to mesothelin (SS1 CAR), we observed limited persistence and efficacy. To improve the outcome, we created a fully human anti-mesothelin scFV fused to the intracellular signaling domains 4-1BB (CD137) and TCR zeta (M5 CAR). Pre-clinical evaluation of the M5 CAR revealed enhanced <i>in vivo</i> antitumor activity compared to the SS1 CAR. <b>Methods:</b> Fourteen patients with mesothelin-expressing tumors (ovarian, lung, malignant mesothelioma) were treated with the M5 CAR. Three patients received a single IV dose of 3 x 10⁷ CART-meso cells/m² (Cohort 1), three patients received a single IV dose of 3 x 10⁷ CART-meso cells/m² following lymphodepletion (Cohort 2), and two patients received a single IV dose of 3 x 10⁸ CART-meso cells/m² (Cohort 3). Due to toxicity, the last six patients received lymphodepletion and an initial IV dose of 3 x 10⁷ CART-meso cells/m² followed by up to two additional IV doses spaced 21-42 days apart (Cohort 4). <b>Results:</b> The infusions were well tolerated. M5 CART cells were detectable in blood one hour after infusion and expanded to a peak at Day 7-10. Higher levels were detected in patients treated with the higher dose CART cells and with lymphodepletion. M5 CART cells persisted up to 28-42 days in all subjects and at three and six months in two patients. M5 CART cells were trafficked to tumors in nine of the 14 patients. At 28-35 days after treatment, eight patients showed stable disease (8/14, 57%) per RECIST criteria. One patient had SD for three months; another had SD for nine months. Four subjects experienced cytokine release syndrome (CRS) (three grade 3 and one grade 4), and related AEs included hypoxia, hypotension, hyponatremia, fatigue, and febrile neutropenia. In Cohort 3, both subjects had acute respiratory SAEs. One patient experienced grade 3 SAEs (CRS, hypotension, hypoxia) but fully recovered. The other patient, with extensive pulmonary tumor burden and residual PD-1 blockade, suffered fatal respiratory failure. Due to these SAEs, the MTD was defined at 3 x 10⁷ CART-meso cells/m² and six subsequent patients had no pulmonary SAEs. <b>Conclusions:</b> This dose-escalation trial demonstrates the feasibility of treating multiple tumor types with M5 CART cells. The M5 CART cells engrafted and expanded in the blood of all subjects but persisted at relatively low blood levels and for short time periods. CART trafficking into tumors was identified in 9/14 patients. Short-term stable disease was noted in the majority of patients, but no clinical responses were seen. Pulmonary toxicity was seen when given at the 3 x 10<b>8</b> CART cells/m² dose. These preliminary results may help guide future M5 CART clinical trials, such as loco-regional delivery or modifications to the CART cells to improve safety and enhance trafficking and persistence.

A Case of Cobra Antivenom Therapy in a Patient Bitten by Elapid Snake in South Korea

Elapid snakes have neurotoxic venom which causes diverse neuroparalytic manifestations, including fatal respiratory failure. In South Korea, since elapid snakebites are very rare, the cobra antivenom, which is effective against neurotoxicity, was only introduced recently. Most physicians in South Korea have little experience in the treatment of patients who have been bitten by elapid snakes. A 19-year-old man was brought to the emergency department with sudden diplopia, 1 hour after a snakebite on the left 2nd finger. The patient presented with drowsiness and complained of mild dizziness and binocular diplopia. After 1 hour, he had sudden onset of dyspnea and dysphagia and appeared to be agitated. He was immediately intubated and received mechanical ventilation as he was unable to breathe on his own. A total of 2.5 mg of neostigmine diluted with normal saline was slowly infused, and 1 vial of cobra antivenom was infused for an hour, 5 times every 2 hours, for a total of 5 vials. He slowly recovered self-breathing; on the 3rd day of hospitalization, he showed tolerable breathing and was extubated. He was discharged without any neurological deficits or other complications.

Particular precautions and the role of intraoperative neuromonitoring in cervical cord injury in elder recreational cyclist: A case report.

Introduction and importanceThe trend in cycling nowadays affects all age groups. However, special precautions must be considered in the elderly group. Minor trauma to the cervical region can cause severe neurological deterioration, leading to fatality because of the pre-existing degenerative process.Case presentationWe present a case of a 61-year-old male recreational cyclist with acute onset of tetraplegia following a minor fall. The radiological result revealed a long-standing degenerative process. Unfortunately, the patient deceased due to the sequelae of the paralysis and cardiac event despite our prompt surgical decompression and the improvement shown on intraoperative neuromonitoring.Clinical discussionThe degenerative process can aggravate cervical cord injury even in its mildest form of injury. In this study, immediate improvement was detected by the intraoperative neuromonitoring (IONM) - although the clinical improvement had not improved yet as the general condition is poor.ConclusionThe elder cycling population is increasing. Safety measures and injury avoidance are advisable along with expert consultation before the exercise. In a pre-existing degenerative condition of the cervical, a special precaution is also needed during the exercise. If the surgery has been indicated, the use of intraoperative neuromonitoring is found to be useful to guide the decompression and potentially beneficial as a predictive value for the clinal outcome.

Spontaneous Pulmonary Hemorrhage Following Thrombolytic Therapy for Acute Myocardial Infarction

Systemic thrombolysis in the setting of acute myocardial infarction (AMI) remains an effective treatment. However, it exposes to a non-negligible bleeding risk Diffuse pulmonary hemorrhage is a of the rare complication of thrombolysis, it can cause a serious medical emergency potentially leading to fatal acute respiratory failure. We present four cases of diffuse pulmonary hemorrhage following administration of intravenous thrombolytic therapy (Tenecteplase), the Lack of recognition that the lungs too may be a site of spontaneous hemorrhage during thrombolytic therapy may lead to a considerable diagnostic and therapeutic delay. Pulmonary hemorrhage should be considered in the differential diagnosis of patients who receive thrombolytic therapy in whom new roentgenographic pulmonary infiltrates present accompanied by decreases in hematocrit value.

Fatal Respiratory Failure in a Term Newborn Due to Non-previously Described Compound Heterozygous ABCA3 Mutations

The adenosine triphosphate binding cassette member A3 (ABCA3) is a lipid transporter involved in pulmonary surfactant biogenesis. ABCA3 deficiency is increasingly being recognized as a cause of respiratory distress syndrome in term neonates. The clinical spectrum and severity of lung disease caused by ABCA3 mutations vary widely. We present a term newborn who presented respiratory distress short afterbirth. Despite treatment and supportive care, she developed a refractory progressive hypoxic respiratory failure and she died. She received repeated surfactant doses always with transient improvement. She was found to be a compound heterozygote for 2 non-previously described ABCA3 gene mutations, one inherited from each parent.