Ventilator Dependence Research Articles

Caloric Intake with High Ratio of Enteral Nutrition Associated with Lower Hospital Mortality for Patients with Acute Respiratory Distress Syndrome Using Prone Position Therapy.

Positioning patients in the prone position leads to reduced hospital mortality rates for those with severe acute respiratory distress syndrome (ARDS). What constitutes the optimal feeding strategy for prone patients with ARDS is controversial. We conducted a retrospective study that enrolled 110 prone patients with ARDS in two medical intensive care units (ICUs) from September 2015 to November 2018. Inclusion criteria were as follows: age ≥20 years, diagnosis of respiratory failure requiring mechanical ventilation, diagnosis of ARDS within 72 h of ICU admission, placement in a prone position within the first 7 days of ICU admission, and ICU stay of more than 7 days. Exclusion criteria were as follows: nil per os orders because of gastrointestinal bleeding or hemodynamic instability, and ventilator dependency because of chronic respiratory failure. The consecutive daily enteral nutrition(EN)/EN + parenteral nutrition(PN) ratio could predict hospital mortality rates within the first 7 days of admission when using generalized estimating equations (p = 0.013). A higher average EN/EN + PN ratio within the first 7 days predicted (hazard ratio: 0.97, confidence interval: 0.96–0.99) lower hospital mortality rates. To reduce hospital mortality rates, caloric intake with a higher EN ratio may be considered for patients in prone positions with ARDS.

CONGENITAL MYOPATHIES – NEMALINE MYOPATHIES: EP.37 ACTA1 congenital myopathy: clinical and genetic spectrum of 5 chilean newborns

Congenital myopathy related with ACTA1 mutation may produce very severe and less severe clinical pictures with different genetic and histopathologic features. We describe clinical and histopathologic features of 5 newborns (two girls) studied between 2013 and 2020 in Clinica Alemana de Santiago and Hospital Luis Calvo Mackenna. Genetic analysis was performed in Hospital Bambino Gesú and Invitae (commercial laboratory USA). The first patient studied (2013) was a girl with fetal akinesia syndrome. She was ventilator dependent since birth, had no movements and presented distal contractures. Histopathology showed myopathic unspecific findings. She died at 6 months of age. Genetic study showed an ACTA 1 de novo mutation. Patients 2 and 3 are boys with neonatal hypotonia, weakness, facial diplegia and mild transient respiratory problems. Patients 2 and 3 had muscle biopsy with cytoplasmic rods. Both showed progressive motor improvement. Genetic analysis showed ACTA1 mutation de novo (patient 2) and autosomal recessive (patient 3). Patient 4 was a girl who showed severe generalized muscular weakness, facial diplegia, ventilatory dependence and progressive dilated myocardiopathy. Muscle biopsy showed type 1 fiber atrophy. Genetic study showed ACTA 1 de novo mutation. She died at 5 months of age. Patient 5, a 1-year-old boy with severe hypotonia and weakness, facial diplegia eyelid ptosis and mechanical ventilator dependent since birth. Muscle biopsy showed unspecific myopathic findings and genetic study detected ACTA 1 de novo mutation. We conclude that de novo ACTA1 mutation correlates with more severe and even fatal outcome (3 out of 4 of our patients) and AR ACTA1 mutation correlates with a more benign outcome (1 of our patients). Finally, muscle histopathology with rods seems to predict a less severe outcome but this is too small a series to validate this hypothesis.

Impact of the COVID-19 Pandemic on Children

Impact of the COVID-19 Pandemic on Children <5 Years of Age With Tracheostomy and Home Ventilator Dependence.

Update: Gender differences in CABG outcomes-Have we bridged the gap?

BackgroundAppreciation of unique presentation, patterns and underlying pathophysiology of coronary artery disease in women has driven gender based risk stratification and risk reduction efforts over the last decade. Data regarding whether these advances have resulted in unequivocal improvements in outcomes of CABG in women is conflicting. The objective of our study was to assess gender differences in post-operative outcomes following CABG.MethodsRetrospective analyses of institutional data housed in the Society of Thoracic Surgeons (STS) database for patients undergoing CABG between 2002 and 2020 were conducted. Multivariable regression analysis was conducted to investigate gender differences in post-operative outcomes. P-values were adjusted using Bonferroni correction to reduce type-I errors.ResultsOur final cohort of 6,250 patients had fewer women than men (1,339 vs. 4,911). more women were diabetic (52.0% vs. 41.2%, p<0.001) and hypertensive (89.1% vs. 84.0%, p<0.001). Women had higher adjusted odds of developing ventilator dependence >48 hours (OR: 1.65 [1.21, 2.45], p = 0.002) and cardiac readmissions (OR: 1.56 [1.27, 2.30], p = 0.003). After adjustment for comorbidity burden, mortality rates in women were comparable to those of age-matched men.ConclusionThe findings of our study indicate that despite apparent reduction of differences in mortality, the burden of postoperative morbidity is still high among women.

Risk factors of surgical mortality in patients with Clostridium difficile colitis. A novel scoring system.

The purpose of the study is to identify the risk factors of mortality and develop a risk scoring system in patients who underwent colectomy due to Clostridium difficile colitis (CD-C). Patient information was extracted using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) data from 2012 to 2016. All adult patients who underwent colectomy for CD-C were included in the study. The data were split into training and testing data sets. A multiple logistic regression model was developed by backward deletion methods for risk assessment. To test the performance of the prediction model for 30-day mortality, a receiver operating characteristic (ROC) curve was generated and an area under the curve (AUC) was created. The training data set consisted of 434 (80%) patients, and the testing data set consisted of 91 (20%) patients. The overall mortality was 35%. No significant differences were found between the training and testing data sets for patient characteristics, comorbidities and mortality. The final model of the logistic regression model revealed a highly significant 30-day mortality for an age of ≥ 75years old, ventilator dependency, Septic shock prior to surgery and a history of steroid use. The AUC value was 0.745 (95% CI 0.660-0.826). The risk of mortality scores range from 0 to 37. The highest score of 37 was related to an 83.9% predicted mortality. Older age, septic shock, ventilator dependency requiring supportive care and a history of chronic steroid use were highly associated with mortality. A nomogram showing the scores and their relationship to mortality may provide guidance to point of care physicians for deciding the goal of care. Level of evidence: IV.

Comprehensive Otolaryngology

Session Description: Every otolaryngologist should know about vaping. Vaping-related harm may include catastrophic lung injury, fatal accidental ingestion in children, explosion of combustible devices, accelerated nicotine addiction, and interaction with COVID-19 risk. Vaping amplifies disparities in use and addiction, mediated through social determinants of health. This panel reveals the evidence around vaping most relevant to practicing otolaryngologists trying to grasp this complex public health concern. We explain vaping epidemiology, sociological undercurrents and disparities, pathophysiology of vapingrelated disease, and what to do about it. We describe how JUUL's meteoric rise to dominance in the electronic cigarette (e-cigarette) space-growth rivaling that of Facebook-was catalyzed by social media, positioning as new technology, stealthy design, and alluring flavors. We probe the science of vaping from surgical wound healing to effects of inhaling formaldehyde, propylene glycol, heavy metals, and other vapors-risks magnified in unregulated cannabinoids. The experiences of individuals who survived vaping-related injury, from respiratory exacerbation to ventilator dependence, is testimony to the crisis. The session offers insights on vaping-related disease, persistent misconceptions, and social determinants of health. e-Cigarettes, a potential “off ramp” for adult smokers have evolved into a heavily trafficked “on ramp” for the next generation. We close with counseling pearls, advice for patients grappling with misinformation, and opportunities for our specialty to lead. Outcome Objectives: (1) Describe trends in electronic nicotine device use, interaction with social determinants of health, current slang used for these habits, and forthcoming inhaled tobacco technology. (2) Describe how sociological factors and biology interact in the pathogenesis of vaping-related respiratory injury and wound healing. (3) Discuss specific talking points for counseling patients and strategies for dispelling misconceptions around vaping-related disease.

Delayed positive COVID19 nasopharyngeal test, a case study with clinical and pathological correlation

BackgroundThere are various reasons for delayed positive nasopharyngeal PCR tests for coronavirus disease 2019 (COVID19) in not only asymptomatic but also severely diseased patients. The pathophysiological attributes are not known. We explore this possibility through a case report.Case presentationA 64-year-old male with history of pulmonary fungal infection, asthma and chronic pulmonary obstructive disease (COPD), diabetes, coronary artery disease presented with shortness of breath, fever and chest image of ground opacity, reticular interstitial thickening, highly suspicious for COVID19. However, nasopharyngeal swab tests were discordantly negative for four times in two weeks, and IgG antibody for COVID19 was also negative. However, serum IgE level was elevated. No other pathogens are identified. His symptoms deteriorated despite corticosteroid, antibiotics and bronchodilator treatment. Bronchoalveolar lavage (BAL) and open lung wedge biopsy were performed for etiology diagnosis. They demonstrated COVID19 viral RNA positive fibrosing organizing pneumonia with respiratory tract damage characterized by suspicious viral cytopathic effect, mixed neutrophilic, lymphoplasmacytic, histiocytic and eosinophilic inflammation and fibrosis besides expected asthma and COPD change. One week later, repeated COVID19 nasopharyngeal tests on day 40 and day 49 became positive.ConclusionOur case and literature review indicate that allergic asthma and associated high IgE level together with corticosteroid inhalation might contribute to the delayed positive nasopharyngeal swab in upper airway; COPD related chronic airways obstruction and the addition of fibrosis induced ventilator dependence and poor prognosis in COVID19 pneumonia, and should be therapeutically targeted besides antiviral therapy.

Catch it before it breaks!: managing metabolic bone disease of prematurity

Metabolic bone disease of prematurity, commonly referred to as osteopenia of prematurity, remains prevalent in the neonatal intensive care unit (NICU) despite recent medical advances. It is estimated that up to 60% of extreme low birth weight and 20% of very low-birth-weight infants have metabolic bone disease of prematurity. Often silent, it typically presents with poor growth, increased ventilator dependency and fractures. Clinical sequalae, such as short stature can extend into young adulthood. There is no universal consensus by neonatal intensive care unit clinicians on the screening, diagnosis, or treatment for metabolic bone disease of prematurity. The disease is often diagnosed late by radiographs or incidentally in this highly fragile population. Suggest screening using DEXA (dual-energy X-ray absorptiometry) scans or ultrasound, in combination with serum markers like alkaline phosphatase, phosphorous levels, parathyroid hormone, and tubular reabsorption of phosphate, might identify at-risk babies earlier. The use of protocol-based screenings may aid in early diagnosis. We present a review of the risk factors, recent screening methods, diagnosis and management of this prevalent, clinically relevant diagnosis, as well as propose a protocol for the early screening and management of this silent disease.

COVID-19 outcomes of 10,881 patients: retrospective study of neurological symptoms and associated manifestations (Philippine CORONA Study)

Our study aimed to determine the effects of new-onset neurological symptoms (NNS) on clinically relevant outcomes in hospitalized patients with COVID-19 infection. We conducted a nationwide, comparative, retrospective, cohort study among adult, hospitalized COVID-19 patients involving 37 hospital sites from various regions in the Philippines. We included a total of 10,881 patients with confirmed COVID-19 infection (2008 had NNS while 8873 did not have NNS). The adjusted hazard ratios (aHRs) for mortality among the mild and severe cases were significantly higher by 1.660 (95% CI 1.132–2.435) and by 1.352 (95% CI 1.042–1.752), respectively, in the NNS group compared to those in the non-NNS group. The aHRs for respiratory failure in the NNS group were significantly increased by 1.914 (95% CI 1.346–2.722), by 1.614 (95% CI 1.260–2.068), and by 1.234 (95% CI 1.089–1.398) among the mild, severe, and critical cases, respectively. The aHRs for ICU admission in the NNS group were still significantly higher by 1.973 (95% CI 1.457–2.673) and by 1.831 (95% CI 1.506–2.226) among the mild and severe cases, respectively. Patients who had NNS were not significantly associated with a longer duration of ventilator dependence (adjusted odds ratio (aOR) 0.954, 95% CI 0.772–1.179), longer ICU stay (aOR 0.983, 95% CI 0.772–1.252) and longer hospital admission (aOR 1.045, 95% CI 0.947–1.153). The presence of NNS significantly increases the risk of mortality, respiratory failure and ICU admission among COVID-19 patients. Registration and associated protocol publication: ClinicalTrials.gov website (NCT04386083); Espiritu AI, Sy MCC, Anlacan VMM, Jamora RDG. The Philippine COVID-19 Outcomes: a Retrospective study Of Neurological manifestations and Associated symptoms (The Philippine CORONA study): a protocol study. BMJ Open. 2020;10:e040944.

Scoliosis in Pediatric Patients With Acute Flaccid Myelitis.

Acute flaccid myelitis (AFM) is an anterior horn disorder that manifests as rapid onset muscle weakness or paralysis. Development of scoliosis in pediatric AFM patients has been anecdotally reported, but associated risk factors or incidence have yet to be determined. Pediatric AFM patients treated over a 10-year period at a tertiary care center were identified. Patients were considered to have scoliosis if there was radiographic evidence of coronal curvature ≥15 degrees. Number of limbs affected, independent ambulation and head control, ventilator requirement at initial admission, and long-term ventilatory support (≥1 year) were recorded. Muscle strength and functional status were assessed by manual muscle testing (MMT) and Physical Abilities and Mobility Scale (PAMS), respectively. Areas of spinal cord lesion on initial MRI were recorded. Bivariate analyses were performed, with alpha set to 0.05. Fifty-six AFM patients (27 scoliosis, 29 no scoliosis) were identified. Mean time from AFM presentation to scoliosis diagnosis was 0.93 years. Mean major Cobb angle at first radiograph was 31.7 ± 14.3 degrees. Lack of independent ambulation, ventilator dependence at time of admission or long term, number of limbs affected, and decreased MMT and PAMS scores were more common in patients who developed scoliosis (all, p < .05). Patients who developed scoliosis had more extensive thoracic spinal cord involvement on initial MRI (p = .03). AFM patients who develop scoliosis are more likely to be ventilator dependent, lack independent ambulation, and have more extensive thoracic SCI.

Postnatal Diagnostic Workup in Children With Arthrogryposis: A Series of 82 Patients.

To describe a postnatal series of patients with arthrogryposis multiplex congenita by the causal mechanisms involved. In this single-center study, the local data warehouse was used to identify patients with arthrogryposis multiplex congenita. Patients were classified into different etiologic groups. Of 82 patients included, the most frequent cause of arthrogryposis multiplex congenita was a neuromuscular disorder (39%), including skeletal muscle (n=19), neuromuscular junction (n=3), and peripheral nerve (n=11) involvement. In other subgroups, 19 patients (23%) were classified by disorders in the central nervous system, 5 (6%) in connective tissue, 7 (8.5%) had mixed mechanisms, and 18 (22%) could not be classified. Contractures topography was not associated with a causal mechanism. Cerebral magnetic resonance imaging (MRI), electroneuromyography, and muscle biopsy were the most conclusive investigations. Metabolic investigations were normal in all the patients tested. Targeted or whole exome sequencing diagnostic rates were 51% and 71%, respectively. Thirty-three percent of patients died (early death occurred in patients with polyhydramnios, prematurity, and ventilatory dependency). The benefits of a precise diagnosis in the neonatal period include more tailored management of arthrogryposis multiplex congenita and better genetic information.

Pediatric surgical rib fixation: A collected case series of a rare entity.

Rib fractures are uncommon in children and are markers of extreme traumatic force from high-energy or nonaccidental etiology. Traditional care includes nonoperative management, with analgesia, ventilator support, and pulmonary physiotherapy. Surgical stabilization of rib fractures (SSRFs) has been associated with improved outcomes in adults. In children, SSRF is performed and its role remains unclear, with data only available from case reports. We created a collected case series of published pediatric SSRF cases, with the aim to provide a descriptive summary of the existing data. Published cases of SSRF following thoracic trauma in patients younger than 18 years were identified. Collected data included demographics, injury mechanism, associated injuries, surgical indication(s), surgical technique, time to extubation, postoperative hospital stay, and postoperative follow-up. Six cases were identified. All were boys, with age range 6 to 16 years. Injury mechanism was high-energy blunt force in all cases, and all patients suffered multiple associated injuries. Five of six cases were related to motor vehicles, and one was horse-related. Indication(s) for surgery included ventilator dependence in five, significant chest deformity in two, and poor pain control in one case. Plating systems were used for rib stabilization in five of six cases, while intramedullary splint was used in one. All patients were extubated within 7 days following SSRF, and all were discharged by postoperative Day 20. On postoperative follow-up, no SSRF-related major issues were reported. One patient underwent hardware removal at 2 months. Surgical stabilization of rib fractures in children is safe and feasible, and should be considered as an alternative to nonoperative therapy in select pediatric thoracic trauma cases. Potential indications for SSRF in pediatric patients include poor pain control, chest wall deformity, or ventilator dependence. Further studies are needed to establish the role and possible benefits of SSRF in pediatric thoracic trauma. Collected case series, level V.

Middle ear disease requiring myringotomy in the first two years after tracheotomy in the pediatric population

ObjectivesRisk factors for middle ear disease necessitating myringotomy with tympanostomy tube placement after a tracheostomy have not been thoroughly explored. This study investigates the incidence and risk factors for ear tube placement in pediatric patients with a tracheostomy. MethodsPediatric patients under age 18 who underwent tracheotomy between 2002 and 2010 at two institutions were identified. Patients were excluded if they had undergone myringotomy prior to, or at the same time as, the tracheotomy, or did not have at least two years of follow-up clinic visits. The presence of other comorbidities was recorded. Descriptive statistics and logistic regression models were used to assess the impact of clinical characteristics on outcomes. ResultsA total of 214 patients met inclusion criteria. Median patient age at time of tracheotomy was 6 months (IQR 2–17), median patient age at time of myringotomy with tubes was 12 months (IQR8-17), and median time between tracheotomy and myringotomy with tube placement was 8 months (IQR 5–11). Sixty-seven (31%) patients required myringotomy with tympanostomy tube placement within the first two years after tracheotomy. Fifty-eight (87%) patients who underwent myringotomy with tympanostomy tubes were younger than 2 years at the time of the procedure. Logistical regression found younger age at time of tracheotomy to be a risk factor (OR: 0.71, 95% CI: 0.5–0.9, p < 0.006). The combination of tracheostomy with gastric tube increased the risk of requiring myringotomy with tubes 2.79 fold (p < 0.009). Craniofacial abnormalities (p < 0.001), known genetic syndrome (p = 0.009), cleft palate (p < 0.001), age at time of tracheotomy (p < 0.001) and gastric tubes (p = 0.002) were all independently found to increase risk of myringotomy with tubes. Patients’ gestational age (p = 0.411), ventilator dependence (p = 0.33), and airway structural abnormalities (p = 0.632) did not increase this risk. ConclusionThis study reports a high incidence of myringotomy with tubes in children with tracheostomy relative to the general pediatric population. Many comorbid conditions that often accompany the need for tracheotomy place these patients at a higher risk for ear disease requiring surgical intervention. Risk factors for operative middle ear disease in this population included age at time of tracheostomy, craniofacial abnormalities, and presence of a G-tube.

Seasonal Variation of Radon Concentrations in Russian Residential High-Rise Buildings

Assessment of the annual radon concentration is often required in indoor radon surveys of territories and individual dwellings for comparison with reference levels, studying factors affecting radon accumulation in dwellings, assessment of exposure in epidemiological studies, etc. The indoor radon surveys were carried out in multistorey buildings in eight Russian cities using solid state nuclear track detectors with an exposure period of three months. For these surveys, the estimation of annual indoor radon concentration was required to compare radon levels in buildings of high- and low-energy-efficiency classes located in different cities. To develop approaches to seasonal normalization in high-rise buildings, long-term one-hour radon concentration series obtained applying radon-monitors in 20 flats were analyzed. The dependency of indoor radon concentration on the indoor–outdoor temperature difference was studied taking into account the known natural, technogenic and anthropogenic factors affecting radon levels. The developed model of seasonal variations in multistorey buildings includes winter, summer, and demi-season periods, which differ both in ventilation intensity and dependency of radon concentration on the temperature difference. The developed model allows to estimate annual radon concentration taking into account the actual distribution of outdoor temperatures during the exposure of the track detectors.

Short-Term Outcomes Following Removal of Infected Hernia Mesh.

There are limited studies regarding outcomes of replacing an infected mesh with another mesh. We reviewed short-term outcomes following infected mesh removal and whether placement of new mesh is associated with worse outcomes. Patients who underwent hernia repair with infected mesh removal were identified from 2005 to 2018 American College of Surgeons-National Surgical Quality Improvement Program database. They were divided into new mesh (Mesh+) or no mesh (Mesh-) groups. Bivariate and multivariate logistic regression analyses were used to compare morbidity between the two groups and to identify associated risk factors. Of 1660 patients, 49.3% received new mesh, with higher morbidity in the Mesh+ (35.9% vs. 30.3%; P = .016), but without higher rates of surgical site infection (SSI) (21.3% vs. 19.7%; P = .465). Mesh+ had higher rates of acute kidney injury (1.3% vs. .4%; P = .028), UTI (3.1% vs. 1.3%, P = .014), ventilator dependence (4.9% vs. 2.4%; P = .006), and longer LOS (8.6 vs. 7days, P < .001). Multivariate logistic regression showed new mesh placement (OR: 1.41; 95% CI: 1.07-1.85; P = .014), body mass index (OR: 1.02; 95% CI: 1.00-1.03; P = .022), and smoking (OR: 1.43; 95% CI: 1.05-1.95; P = .025) as risk factors independently associated with increased morbidity. New mesh placement at time of infected mesh removal is associated with increased morbidity but not with SSI. Body mass index and smoking history continue to contribute to postoperative morbidity during subsequent operations for complications.

Submandibular Gland Excision in Pediatric Patients.

Children who require submandibular gland excision for ptyalism often have multiple associated comorbidities, including neurodevelopmental disorders and respiratory risk factors. The purpose of this study is to utilize a large multicenter database to elucidate the perioperative profile of submandibular gland excision in children, with particular focus on children who require submandibular gland excision for ptyalism. The American College of Surgeons National Surgical Quality Improvement Program Pediatric dataset was queried for submandibular gland excision performed from 2012 through 2018. Indications were subclassified based on International Classification of Disease (ICD)-9 and ICD-10 codes. Complications, readmissions, and reoperations were analyzed with appropriate statistics. During the study interval, 304 pediatric patients underwent submandibular gland excision, which was mostly performed for ptyalism (56.9%), followed by inflammatory conditions (20.7%). Patients requiring submandibular gland excision for ptyalism were significantly younger (P < 0.001) and underwent significantly longer procedures (P < 0.001). Ptyalism was associated with significantly higher related adverse events (P = 0.010), related readmission (P = 0.013), and medical complications (P = 0.013), which included a significantly higher risk of pneumonia (P = 0.050). Children with ptyalism had significantly higher rates of overall respiratory comorbidities (P < 0.001), including chronic lung disease (P < 0.001), supplemental oxygen support (P < 0.001), tracheostomy (P < 0.001), and ventilator dependence (P < 0.001). Patients undergoing submandibular gland excision for benign (P all ≥ 0.082) and malignant (P all ≥ 0.565) neoplasms did not have significantly higher rates of any indexed postoperative adverse event. Children requiring submandibular gland excision for ptyalism represent a unique cohort than those requiring excision for other indications, with significantly higher burden of preoperative risk factors, intraoperative durations, and postoperative adverse events.

The Combination of SOFA Score and Urinary NGAL May Be an Effective Predictor for Ventilator Dependence among Critically Ill Surgical Patients: A Pilot Study.

Background: Ventilator dependence (VD) has been considered as a serious complication in critically ill patients in the intensive care unit (ICU). Acute kidney injury (AKI) is associated with VD as a result of lung–kidney interaction. The aim of our study was to investigate novel biomarkers in predicting ventilator dependence in critically ill surgical patients. Methods: Patients who were admitted to surgical ICU were enrolled and their serum and urine samples were collected. Novel biomarkers including gelatinase-associated lipocalin (NGAL), calprotectin, kidney injury molecule-1 (KIM-1), cystatin C, and growth differentiation factor 15 (GDF-15) were analyzed and correlated with clinical outcome. Results: A total of 33 patients were enrolled and analyzed. The majority of them received abdominal surgery prior to ICU admission. Thirteen patients were classified into the VD group, while the remaining 20 were in a non-ventilator dependence group (nVD). Statistical analysis demonstrated that the following were significantly higher in the VD group than in the nVD group: serum NGAL (420.25 ± 45.18 ng/mL vs. 314.68 ± 38.12 ng/mL, p-value 0.036), urinary NGAL (420.87 ± 41.08 ng/mL vs. 250.84 ± 39.45 ng/mL, p-value 0.002), SOFA score (11.3 ± 1.5 vs. 5.6 ± 0.7, p-value 0.001), and APACHE II score (23.2 ± 2.6 vs. 13.6 ± 0.8, p-value 0.001). The area under the ROC curve (AUROC) of urinary NGAL for VD was 0.808. The combination of urinary NGAL and SOFA score could further increase AUROC for VD to 0.835. Conclusions: The current study demonstrated the predictive capability of urinary NGAL for ventilator dependence among critically ill surgical patients. When combined with SOFA score, the predictive ability was further augmented. Further large-scale studies are warranted to validate our findings.

Soluble Suppression of Tumorigenicity-2 Associates With Ventilator Dependence in Coronavirus Disease 2019 Respiratory Failure.

We hypothesize that elevated soluble suppression of tumorigenicity-2 concentrations, a marker of pulmonary epithelial injury, reflect ongoing lung injury in acute hypoxemic respiratory failure due to coronavirus disease 2019 and associate with continued ventilator dependence. We associated serial plasma soluble suppression of tumorigenicity-2 levels and markers of systemic inflammation including d-dimer, C-reactive protein, and erythrocyte sedimentation rate with 30-day mortality and ventilator dependence. Adult medical ICUs and general medicine wards at an academic teaching hospital in Boston, MA. Adult patients with severe acute respiratory syndrome coronavirus 2 infection and acute hypoxemic respiratory failure admitted to the ICU (n = 72) and non-ICU patients managed with supplemental oxygen (n = 77). Observational study from April 25 to June 25, 2020. ICU patients had a higher baseline body mass index and median soluble suppression of tumorigenicity-2, d-dimer, and C-reactive protein concentrations compared with non-ICU patients. Among ICU patients, elevated baseline modified Sequential Organ Failure Assessment score and log (soluble suppression of tumorigenicity-2) were associated with 30-day mortality, whereas initial Pao2/Fio2 and markers of systemic inflammation were similar between groups. Only log (soluble suppression of tumorigenicity-2) associated with ventilator dependence over time, with the last measured log (soluble suppression of tumorigenicity-2) concentration obtained on ICU day 11.5 (interquartile range [7-17]) higher in patients who required reintubation or tracheostomy placement compared with patients who were successfully extubated (2.10 [1.89-2.26] vs 1.87 ng/mL [1.72-2.13 ng/mL]; p = 0.03). Last measured systemic inflammatory markers, modified Sequential Organ Failure Assessment score, and Pao2/Fio2 were not different between patients who were successfully extubated compared with those with continued ventilator dependence. Plasma soluble suppression of tumorigenicity-2 is a biomarker readily measured in blood that can provide dynamic information about the degree of a patient's lung injury and real-time assessment of the likelihood of extubation success. Measures of systemic inflammation, illness severity, and oxygenation did not associate with ventilator outcomes.

Pooled Analysis of Day +100 Survival for Defibrotide-Treated Patients with Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) and Ventilator or Dialysis Dependence Following Hematopoietic Stem Cell Transplantation (HSCT)

BackgroundVOD/SOS is an unpredictable, potentially life-threatening complication of conditioning regimens for HSCT or chemotherapy without HSCT, and has been reported to have an overall incidence of 13.7% post-HSCT. VOD/SOS with multi-organ dysfunction (MOD) may be associated with >80% mortality. In the United States, defibrotide is approved for the treatment of adult and pediatric patients with hepatic VOD/SOS and renal or pulmonary dysfunction following HSCT, and it is approved in the European Union for treatment of severe hepatic VOD/SOS after HSCT. Here, a pooled analysis compared overall survival among groups based on severity of VOD/SOS, including those with MOD and those who were ventilator- or dialysis-dependent.MethodsThis analysis included data from a phase 2 trial, a phase 3 trial, and an expanded-access (T-IND) program. The phase 2 dose-finding trial (defibrotide 25 mg/kg/day [n=75] and 40 mg/kg/day [n=74]) in patients with VOD/SOS and MOD found no significant differences in efficacy or safety between doses. The phase 3 treatment trial compared the efficacy and safety of defibrotide at 25 mg/kg/day in patients with VOD/SOS with MOD (n=102) to those of patients from a historical control group (n=32) that met the study's inclusion criteria but were treated at the study's centers prior to the availability of defibrotide at that institution. The T-IND study provided access to 25 mg/kg/day defibrotide prior to regulatory approval in the United States and generated prospective data on outcomes in 1154 VOD/SOS patients with and without MOD following HSCT or chemotherapy without HSCT. Data from patients with VOD/SOS and MOD (renal or pulmonary dysfunction, Table 1) following HSCT were pooled to examine Day +100 survival in relationship to MOD severity, with dialysis and ventilator dependence at baseline indicating the most severe dysfunction.ResultsThe total pooled population from the 3 trials was 763 patients with VOD/SOS and MOD post-HSCT (phase 2 trial, n=149; phase 3 trial, n=102; T-IND study, n=512). Of these, 219 (28.7%) patients had ventilator dependence (irrespective of dialysis dependence) and 172 (22.5%) patients had dialysis dependence (irrespective of ventilator dependence; Table 2). A total of 275 patients had either dependence (ie, at least one) and 116 had both dependencies. The 32 historical control patients from the phase 3 trial were analyzed separately (Table 2). Median age in the pooled treatment population was 17 (range, 0-72) years and 18 (range, 1-57) in the historical controls.Kaplan-Meier Day +100 estimated survival rate was 51.9% (95% confidence interval [CI], 47.3%-56.3%) in patients with neither dependence (n=488). In the 275 patients with either dependence, Kaplan-Meier Day +100 estimated survival was 36.3% (95% CI, 30.6%-42.0%); and in patients with both dependencies (n=116), Kaplan-Meier Day +100 estimated survival was 29.1% (95% CI, 21.1%-37.6%).In the 32-patient historical control group, Kaplan-Meier Day +100 estimated survival rates were: 28.0% (95% CI, 12.4%-46.0%) in patients with neither dependence (n=25) and 14.3% (95% CI, 0.7%-46.5%) in patients with at least one dependence (n=7). One patient in this group had both ventilator and dialysis dependence and died prior to Day +100.In the pooled group of treated patients, 627 (82.2%) had at least one adverse event, with 196 (25.7%) having a treatment-related adverse event (TRAE). The most common TRAEs (>2% of the population) were: hypotension, 4.1%; gastrointestinal hemorrhage, 3.9%; pulmonary hemorrhage, 3.9%; epistaxis, 2.8%; and pulmonary alveolar hemorrhage, 2.0%. Hemorrhagic events were reported in 40.6%; hypotension in 22.7%. All 32 historical patients had at least one adverse event.ConclusionsResults from this pooled analysis of patients with VOD/SOS with MOD from 3 defibrotide studies suggest that survival outcomes are better when the treated patients have less severe forms of MOD (51.9%) vs patients with ventilator and/or dialysis dependence (36.3%) vs both ventilator plus dialysis dependence (29.1%). In the small historical control population, Day +100 survival in patients without ventilator or dialysis dependence was 28.0% and was 14.3% in patients with ventilator and/or dialysis dependence.Support: Jazz Pharmaceuticals. [Display omitted] DisclosuresRichardson:Oncopeptides AB: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Research Funding. Kernan:Gentium: Other: Received grants from Gentium during the conduct of the study and research was supported by The National Cancer Institute of the National Institutes of Health under award number P30 CA 008748, Research Funding. Antin:Gentium SpA/Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Ryan:Celator/Jazz: Employment, Equity Ownership. Hume:Jazz Pharmaceuticals, Inc.: Employment, Other: stock options. Tappe:Jazz Pharmaceuticals, Inc.: Employment, Other: stock options. Grupp:University of Pennsylvania: Patents & Royalties; Jazz Pharmaceuticals: Consultancy; Novartis Pharmaceuticals Corporation: Consultancy, Other: grant; Adaptimmune: Consultancy.

Spinal toxoplasmosis in a young man with undiagnosed HIV infection

Spinal cord lesions are potentially devastating conditions leading to reduced mobility, loss of functional independence, and even ventilator dependence, dictated by the level of injury. Tissue diagnosis is paramount to differentiate between primary brain tumours such as ependymomas and glioblastomas, infarction, infection and demyelination. We present the case of a 30-year-old gentleman with subacute neck pain, nausea and evolving right upper limb weakness and paraesthesiae. MRI-spine demonstrated an intramedullary cervical spine mass with associated oedema, thought to represent an ependymoma. Open tissue biopsy revealed numerous bradyzoites on haematoxylin & eosin staining, subsequently confirmed by directed polymerase chain reaction testing as Toxoplasma gondii. Detailed immunological work-up led to a diagnosis of HIV infection, with detection of HIV antibodies and HIV-1 p24 antigen, an HIV-1 viraemia (log 6.33 copies/mL) and low CD4 count (16 cells/mL). Toxoplasmosis is the most common central nervous system infection in HIV patients not receiving appropriate prophylaxis.1 It may occur in up to 30% of such patients who are seropositive for Toxoplasma gondii,2 typically manifesting when CD4+ counts fall below 100 cells/mm3.3 This case highlights the importance of close collaboration between histopathology, microbiology and infectious diseases specialists in diagnosis of a spinal cord infection with associated HIV infection. 1.Porter SB, Sande MA. Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome. N Engl J Med 1992; 327: 1643–8.2.Grant IH, Gold JW, Rosenblum M, et al. Toxoplasma gondii serology in HIV-infected patients: the development of central nervous system toxoplasmosis in AIDS. AIDS 1990; 4: 519–21.3.Kaplan JE, Benson C, Holmes KK, et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. MMWR Recomm Rep 2009; 58: 1–207.