Concurrent abnormal non-acid reflux is associated with additional chronic rejection risk in lung transplant patients with increased acid exposure.

Acid reflux has been associated with allograft injury and rejection in lung transplant patients; however, the pathogenic role of non-acid reflux remains debated. We aimed to evaluate the impact of concurrent abnormal non-acid reflux with acid reflux on chronic rejection in lung transplant patients with acid reflux. This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined impedance-pH study off acid suppression. Only subjects with acid exposure >4% were included. Non-acid reflux (pH > 4) episodes >27 was considered abnormal per prior normative studies. Chronic rejection was defined as chronic lung allograft dysfunction (CLAD) per International Society for Heart and Lung Transplantation criteria. Time-to-event analyses were performed using Cox proportional hazards and Kaplan-Maier methods, with censoring at death, anti-reflux surgery, or last follow-up. In total, 68 subjects (28 abnormal/40 normal non-acid reflux) met inclusion criteria for the study. Baseline demographic/clinical characteristics were similar between groups. Among this cohort of patients with increased acid exposure, subjects with concurrent abnormal non-acid reflux had significantly higher risk of CLAD than those without on Kaplan-Meier analysis (log-ranked P = 0.0269). On Cox multivariable regression analysis controlling for body mass index, age at transplantation, and proton pump inhibitor use, concurrent abnormal non-acid reflux remained independently predictive of increased CLAD risk (hazard ratio 2.31, confidence interval: 1.03-5.19, P = 0.04). Presence of concurrent abnormal non-acid reflux in lung transplant subjects with increased acid exposure is associated with additional risk of chronic rejection. Non-acid reflux may also contribute to pathogenicity in lung allograft injury/rejection, supporting a potential role for impedance-based testing in this population.

Evaluation of the SARC-F Questionnaire as a Diagnostic Tool for Sarcopenia in Geriatric Age-group in India.

INTRODUCTION: With medical science advancing in leaps and bounds, average lifespan is now trending upward, and we are now facing an increasing prevalence of diseases of the elderly, sarcopenia being one of them. Unfortunately, sarcopenia, especially in India, remains to be frequently overlooked, underdiagnosed, and largely understudied. One of the greatest hindrances to the diagnosis of sarcopenia is high costs and limited availability of diagnostic modalities such as magnetic resonance imaging (MRI) and dual energy X-ray absorptiometry (DEXA) scan. Accessible, feasible, and affordable means to diagnose sarcopenia is thus the need of the hour. MATERIALS AND METHODS: We performed a cross-sectional observational study among 300 patients aged 65 years or above (including both outpatient and inpatient departments) at MM Institute of Medical Sciences, Mullana between June 2021 and June 2022. Patients were evaluated as per the European Working Group for Sarcopenia in Older People (EWGSOP) algorithm using bioelectrical impedance analysis (BIA) and the results were compared with results of the SARC-F questionnaire. Statistical analyses were then carried out using IBM Statistical Package for the Social Sciences (SPSS) Statistics version 26. RESULTS: Out of 300 patients, 56 (18.7%) were sarcopenic. Sarcopenia showed no significant association with sex (p = 0.74). SARC-F showed a sensitivity of 73.2% and a specificity of 37.3% with a positive predictive value of 86.51% and a negative predictive value of 32.84% in diagnosing sarcopenia. SARC-F showed good internal reliability with a Cronbach's α > 0.7. CONCLUSION: The SARC-F questionnaire can be used as a bedside screening tool for sarcopenia, especially in a developing country like India where diagnostic resources are frequently scarce.

Differences in airway microbiome and metabolome of single lung transplant recipients.

BACKGROUND: Recent studies suggest that alterations in lung microbiome are associated with occurrence of chronic lung diseases and transplant rejection. To investigate the host-microbiome interactions, we characterized the airway microbiome and metabolome of the allograft (transplanted lung) and native lung of single lung transplant recipients. METHODS: BAL was collected from the allograft and native lungs of SLTs and healthy controls. 16S rRNA microbiome analysis was performed on BAL bacterial pellets and supernatant used for metabolome, cytokines and acetylated proline-glycine-proline (Ac-PGP) measurement by liquid chromatography-high-resolution mass spectrometry. RESULTS: In our cohort, the allograft airway microbiome was distinct with a significantly higher bacterial burden and relative abundance of genera Acinetobacter & Pseudomonas. Likewise, the expression of the pro-inflammatory cytokine VEGF and the neutrophil chemoattractant matrikine Ac-PGP in the allograft was significantly higher. Airway metabolome distinguished the native lung from the allografts and an increased concentration of sphingosine-like metabolites that negatively correlated with abundance of bacteria from phyla Proteobacteria. CONCLUSIONS: Allograft lungs have a distinct microbiome signature, a higher bacterial biomass and an increased Ac-PGP compared to the native lungs in SLTs compared to the native lungs in SLTs. Airway metabolome distinguishes the allografts from native lungs and is associated with distinct microbial communities, suggesting a functional relationship between the local microbiome and metabolome.

COVID-19 patient bridged to recovery with veno-venous extracorporeal membrane oxygenation.

BACKGROUND: In severe cases, the coronavirus disease 2019 (COVID-19) viral pathogen produces hypoxic respiratory failure unable to be adequately supported by mechanical ventilation. The role of extracorporeal membrane oxygenation (ECMO) remains unknown, with the few publications to date lacking detailed patient information or management algorithms all while reporting excessive mortality. METHODS: Case report from a prospectively maintained institutional ECMO database for COVID-19. RESULTS: We describe veno-venous (VV) ECMO in a COVID-19-positive woman with hypoxic respiratory dysfunction failing mechanical ventilation support while prone and receiving inhaled pulmonary vasodilator therapy. After 9 days of complex management secondary to her hyperdynamic circulation, ECMO support was successfully weaned to supine mechanical ventilation and the patient was ultimately discharged from the hospital. CONCLUSIONS: With proper patient selection and careful attention to hemodynamic management, ECMO remains a reasonable treatment option for patients with COVID-19.

Xanthine oxidase of Acinetobacter calcoaceticus RL2-M4: Production, purification and characterization.

Xanthine oxidase (EC 1.17.3.2) is a key enzyme of purine metabolism and has potential applications in food and pharmaceutical industries. In the present study, a new bacterial source of xanthine oxidase i.e. Acinetobacter calcoaceticus RL2-M4 with high oxidase activity was isolated from soil. The culture conditions were optimized with one variable at a time (OVAT) and response surface methodology (RSM) approaches included: a minimal salt medium (MSM) of pH 7.0 supplemented with 0.8% yeast extract, 8.5 mM xanthine and incubation at 30 °C for 24 h. Under these culture conditions 11.57 fold increase in the production of this enzyme was achieved. The enzyme was purified from A. calcoaceticus RL2-M4 using anion exchange chromatography to 8.18 fold with 31% yield and specific activity of 4.58 U/mg protein. SDS-PAGE analysis of the purified enzyme revealed that it was homodimer of 95 kDa and its native molecular mass was estimated to be 190 kDa. This enzyme was found to be stable at 35 °C for 5 h. The purified xanthine oxidase of A. calcoaceticus RL2-M4 had Km 0.3 mM and Vmax 5.8 U/mg protein using xanthine as substrate. The activity and stability characteristic of xanthine oxidase of A. calcoaceticus RL2-M4 makes it a potentially good enzyme for industrial applications.

Nanoparticle drug delivery characterization for fluticasone propionate and in vitro testing 1.

Glucocorticoids, such as fluticasone propionate (FP), are used for the treatment of inflammation and alleviation of nasal symptoms and allergies, and as an antipruritic. However, both short- and long-term therapeutic use of glucocorticoids can lead to muscle weakness and atrophy. In the present study, we evaluated the feasibility of the nanodelivery of FP with poly(dl-lactide-co-glycolide) (PLGA) and tested in vitro function. FP-loaded PLGA nanoparticles were prepared via nanoprecipitation and morphological characteristics were studied via scanning electron microscopy. FP-loaded nanoparticles demonstrated an encapsulation efficiency of 68.6% ± 0.5% with a drug loading capacity of 4.6% ± 0.04%, were 128.8 ± 0.6 nm in diameter with a polydispersity index of 0.07 ± 0.008, and displayed a zeta potential of -19.4 ± 0.7. A sustained in vitro drug release pattern was observed for up to 7 days. The use of fluticasone nanoparticle decreased lipopolysaccharide (LPS)-induced lactate dehydrogenase release compared with LPS alone in C2C12 treated cells. FP also decreased expression of LPS-induced inflammatory genes in C2C12 treated cells as compared with LPS alone. Taken together, the present study demonstrates in vitro feasibility of PLGA-FP nanoparticle delivery to the skeletal muscle cells, which may be beneficial for treating inflammation.

The neutrophil chemoattractant peptide proline-glycine-proline is associated with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is characterized by unrelenting polymorphonuclear neutrophil (PMN) inflammation and vascular permeability. The matrikine proline-glycine-proline (PGP) and acetylated PGP (Ac-PGP) have been shown to induce PMN inflammation and endothelial permeability in vitro and in vivo. In this study, we investigated the presence and role of airway PGP peptides in acute lung injury (ALI)/ARDS. Pseudomonas aeruginosa-derived lipopolysaccharide (LPS) was instilled intratracheally in mice to induce ALI, and increased Ac-PGP with neutrophil inflammation was noted. The PGP inhibitory peptide, arginine-threonine-arginine (RTR), was administered (it) 30 min before or 6 h after LPS injection. Lung injury was evaluated by detecting neutrophil infiltration and permeability changes in the lung. Pre- and posttreatment with RTR significantly inhibited LPS-induced ALI by attenuating lung neutrophil infiltration, pulmonary permeability, and parenchymal inflammation. To evaluate the role of PGP levels in ARDS, minibronchoalveolar lavage was collected from nine ARDS, four cardiogenic edema, and five nonlung disease ventilated patients. PGP levels were measured and correlated with Acute Physiology and Chronic Health Evaluation (APACHE) score, PaO2 to FIO2 (P/F), and ventilator days. PGP levels in subjects with ARDS were significantly higher than cardiogenic edema and nonlung disease ventilated patients. Preliminary examination in both ARDS and non-ARDS populations demonstrated PGP levels significantly correlated with P/F ratio, APACHE score, and duration on ventilator. These results demonstrate an increased burden of PGP peptides in ARDS and suggest the need for future studies in ARDS cohorts to examine correlation with key clinical parameters.

ECG Changes in Young Healthy Smokers: A Simple and Cost-Effective Method to Assess Cardiovascular Risk According to Pack-Years of Smoking.

OBJECTIVE: To document the prevalence of ECG abnormalities in young healthy smokers and compare ECG changes in smokers, young healthy non-smokers and amongst smokers with different pack years. METHODS: This was a prospective case-control study consisting of 200 young healthy male and female individuals, 150 smokers and 50 non-smokers between ages 25-40 years, further categorized and compared according to age, sex and pack years of smoking. The ECG recordings were analyzed for different ECG parameters like heart rate, P-wave duration, P-wave amplitude, PR interval, QRS duration, RR-interval, ST-segment duration, QT interval and QTc interval. The results were compared using statistical tools. RESULTS: In present study abnormalities in ECG parameters were significantly more prevalent in smokers as compared to non-smokers (56.66 % Vs 6.00 %) (p <.0001). Heart rate and QTc-interval increased with increase in the number of pack-years. This increase was reflected more in female with a similar number of pack years. P-wave amplitude tended to increase with increase in the number of pack years more so in males. P-wave duration, PR-interval, QRS-duration and RR-interval tended to decrease with increase in the number of pack years more so in females with similar number of pack years. QT-interval and ST-segment duration tended to decrease with increase in the number of pack years more so in males. CONCLUSIONS: ECG abnormalities in this study indicate cardiovascular risk in term of cardiac arrhythmia, pulmonary arterial hypertension, heart blocks etc in such subjects. As this procedure is non-invasive and cost effective it is potentially an effective and yet a simple method for cardiovascular risk evaluation in smokers. Furthermore, such ECG abnormalities may guide the clinician for risk evaluation in smokers and may be used to convince the smokers to quit smoking.

Thermostable Xanthine Oxidase Activity from Bacillus pumilus RL-2d Isolated from Manikaran Thermal Spring: Production and Characterization.

Xanthine oxidase is an important enzyme of purine metabolism that catalyzes the hydroxylation of hypoxanthine to xanthine and then xanthine to uric acid. A thermostable xanthine oxidase is being reported from a thermophilic organism RL-2d isolated from the Manikaran (Kullu) hot spring of Himachal Pradesh (India). Based on the morphology, physiological tests, and 16S rDNA gene sequence, RL-2d was identified as Bacillus pumilus. Optimization of physiochemical parameters resulted into 4.1-fold increase in the xanthine oxidase activity from 0.051 U/mg dcw (dry cell weight) to 0.209 U/mg dcw. The xanthine oxidase of B. pumilus RL-2d has exhibited very good thermostability and its t1/2 at 70 and 80 °C were 5 and 1 h, respectively. Activity of this enzyme was strongly inhibited by Hg(2+), Ag(+) and allopurinol. The investigation showed that B. pumilus RL-2d exhibited highest xanthine oxidase activity and remarkable thermostability among the other xanthine oxidases reported so far.

Acute ischaemic stroke and acute myocardial infarction occurring together in domestic low-voltage (220-240V) electrical injury: a rare complication.

BACKGROUND: Myocardial Infarction and Ischaemic stroke are potential outcome after an electric shock though it is seen relatively rarely. CASE REPORT: Here, we report a man with myocardial infarction as well as Ischaemic stroke occurring together who suffered a domestic low- voltage (220-240V) electrical injury. Myocardial infarction was evident by cardiac enzymes, electrocardiography and echocardiography while Ischemic stroke was evident on CT scan head: Patient was treated on line of acute ischaemic stroke and myocardial infarction. Patient was discharged in satisfactory condition. CONCLUSION: Electric Injury due to low voltage AC may cause ischaemic stroke as well as myocardial Infarction altogether. Vasospasm caused by electrical injury, direct thermal injury may be the cause of concurrent phenomenon.

Leukemia inhibitory factor (LIF) receptor amplifies pathogenic activation of fibroblasts in lung fibrosis.

Fibrosis drives end-organ damage in many diseases. However, clinical trials targeting individual upstream activators of fibroblasts, such as TGFß, have largely failed. Here, we target the leukemia inhibitory factor receptor (LIFR) as a "master amplifier" of multiple upstream activators of lung fibroblasts. In idiopathic pulmonary fibrosis (IPF), the most common fibrotic lung disease, we found that lung myofibroblasts had high LIF expression. Further, TGFß1, one of the key drivers of fibrosis, upregulated LIF expression in IPF fibroblasts. In vitro anti-LIFR antibody blocking on human IPF lung fibroblasts reduced induction of profibrotic genes downstream of TGFß1, IL-4 and IL-13. Further, siRNA silencing of LIFR in IPF precision cut lung slices reduced expression of fibrotic proteins. Together, we find that LIFR drives an autocrine positive feedback loop that amplifies and sustains pathogenic activation of IPF fibroblasts downstream of multiple external stimuli, implicating LIFR as a therapeutic target in fibrosis. Significance Statement: Fibroblasts have a central role in the pathogenesis of fibrotic diseases. However, due to in part to multiple profibrotic stimuli, targeting a single activator of fibroblasts, like TGFß, has not yielded successful clinical treatments. We hypothesized that a more effective therapeutic strategy is identifying a downstream "master amplifier" of a range of upstream profibrotic stimuli. This study identifies the leukemia inhibitory factor receptor (LIFR) on fibrotic lung fibroblasts amplifies multiple profibrotic stimuli, such as IL-13 and TGFß. Blocking LIFR reduced fibrosis in ex vivo lung tissue from patients with idiopathic pulmonary fibrosis (IPF). LIFR, acting as a master amplifier downstream of fibroblast activation, offers an alternative therapeutic strategy for fibrotic diseases.

Pre-Lung transplant reflux testing demonstrates high prevalence of gastroesophageal reflux in cystic fibrosis and reduces chronic rejection risk.

BACKGROUND: Gastroesophageal reflux (GER) has been associated with poor outcomes after lung transplantation for chronic lung disease, including increased risk of chronic rejection. GER is common in cystic fibrosis (CF), but factors influencing the likelihood of pre-transplant pH testing, and the impact of testing on clinical management and transplant outcomes in patients with CF are unknown. AIM: To evaluate the role of pre-transplant reflux testing in the evaluation of lung transplant candidates with CF. METHODS: This was a retrospective study from 2007-2019 at a tertiary medical center that included all patients with CF undergoing lung transplant. Patients with pre-transplant anti-reflux surgery were excluded. Baseline characteristics (age at transplantation, gender, race, body mass index), self-reported GER symptoms prior to transplantation, and pre-transplant cardiopulmonary testing results, were recorded. Reflux testing consisted of either 24-h pH- or combined multichannel intraluminal impedance and pH monitoring. Post-transplant care included a standard immunosuppressive regimen, and regular surveillance bronchoscopy and pulmonary spirometry in accordance with institutional practice as well as in symptomatic patients. The primary outcome of chronic lung allograft dysfunction (CLAD) was defined clinically and histologically per International Society of Heart and Lung Transplantation criteria. Statistical analysis was performed with Fisher's exact test to assess differences between cohorts, and time-to-event Cox proportional hazards modeling. RESULTS: After applying inclusion and exclusion criteria, a total of 60 patients were included in the study. Among all CF patients, 41 (68.3%) completed reflux monitoring as part of pre-lung transplant evaluation. Objective evidence of pathologic reflux, defined as acid exposure time > 4%, was found in 24 subjects, representing 58% of the tested group. CF patients with pre-transplant reflux testing were older (35.8 vs 30.1 years, P = 0.01) and more commonly reported typical esophageal reflux symptoms (53.7% vs 26.3%, P = 0.06) compared to those without reflux testing. Other patient demographics and baseline cardiopulmonary function did not significantly differ between CF subjects with and without pre-transplant reflux testing. Patients with CF were less likely to undergo pre-transplant reflux testing compared to other pulmonary diagnoses (68% vs 85%, P = 0.003). There was a decreased risk of CLAD in patients with CF who underwent reflux testing compared to those who did not, after controlling for confounders (Cox Hazard Ratio 0.26; 95%CI: 0.08-0.92). CONCLUSION: Pre-transplant reflux testing revealed high prevalence of pathologic reflux in CF patients and was associated with decreased risk of CLAD. Systematic reflux testing may enhance outcomes in this patient population.

Ineffective esophageal motility is associated with acute rejection after lung transplantation independent of gastroesophageal reflux.

BACKGROUND: Gastroesophageal reflux is associated with poorer outcomes after lung transplant, likely through recurrent aspiration and allograft injury. Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes, the role of esophageal manometry in the assessment of lung transplant patients remains debated, and the impact of esophageal dysmotility on transplant outcomes is unclear. Of particular interest is ineffective esophageal motility (IEM) and its associated impact on esophageal clearance. AIM: To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation. METHODS: This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018. Patients with pre-transplant anti-reflux surgery were excluded. Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing. Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection, defined histologically per International Society of Heart and Lung Transplantation guidelines. Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery, last clinic visit, or death. Fisher's exact test for binary variables and student's t-test for continuous variables were performed to assess for differences between groups. RESULTS: Of 184 subjects (54% men, mean age: 58, follow-up: 443 person-years) met criteria for inclusion. Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis (41%). During the follow-up period, 60 subjects (33.5%) developed acute rejection. The all-cause mortality was 16.3%. Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection [hazard ratio (HR): 1.984, 95%CI: 1.03-3.30, P = 0.04], confirmed on Kaplan-Meier curve. On multivariable analysis, IEM remained independently associated with acute rejection, even after controlling for potential confounders such as the presence of acid and nonacid reflux (HR: 2.20, 95%CI: 1.18-4.11, P = 0.01). Nonacid reflux was also independently associated with acute rejection on both univariate (HR: 2.16, 95%CI: 1.26-3.72, P = 0.005) and multivariable analyses (HR: 2.10, 95%CI: 1.21-3.64, P = 0.009), adjusting for the presence of IEM. CONCLUSION: Pre-transplant IEM was associated with acute rejection after transplantation, even after controlling for acid and nonacid reflux. Esophageal motility testing may be considered in lung transplant to predict outcomes.

Routine Reflux Testing Guides Timely Antireflux Treatment to Reduce Acute and Chronic Rejection After Lung Transplantation.

INTRODUCTION: Gastroesophageal reflux has been associated with poorer lung transplantation outcomes, although no standard approach to evaluation/management has been adopted. We aimed to evaluate the effect of timely antireflux treatment as guided by routine reflux testing on postlung transplant rejection outcomes. METHODS: This was a retrospective cohort study of lung transplant recipients at a tertiary center. All patients underwent pretransplant ambulatory pH monitoring. Timely antireflux treatment was defined as proton pump inhibitor initiation or antireflux surgery within 6 months of transplantation. Patients were separated into 3 groups: normal pH monitoring (-pH), increased reflux (+pH) with timely treatment, and +pH with delayed treatment. Rejection outcomes included acute rejection, bronchiolitis obliterans syndrome, and chronic lung allograft dysfunction per International Society for Heart and Lung Transplantation criteria. Time-to-event analyses using Cox proportional hazard models were applied. Patients not meeting outcomes were censored at death or last clinic visit. RESULTS: One hundred seventy-five patients (59% men/mean 56.3 yr/follow-up: 496 person-years) were included. On multivariable analyses, +pH/delayed treatment patients had higher risks of acute rejection (adjust hazard ratio [aHR]:3.81 [95% confidence interval [CI]: 1.90-7.64], P = 0.0002), bronchiolitis obliterans syndrome (aHR: 2.22 [95% CI: 1.07-4.58], P = 0.03), and chronic lung allograft dysfunction (aHR: 2.97 [95% CI: 1.40-6.32], P = 0.005) than +pH/timely treatment patients. Similarly, rejection risks were increased among +pH/delayed treatment patients vs -pH patients (all P < 0.05). No significant differences in rejection risks were noted between +pH/timely treatment patients and -pH patients. Failure/complications of antireflux treatment were rare and similar among groups. DISCUSSION: Timely antireflux treatment, as directed by pretransplant reflux testing, was associated with reduced allograft rejection risks and demonstrated noninferiority to patients without reflux. A standardized peri-transplant test-and-treat algorithm may guide timely reflux management to improve lung transplant outcomes.

Esophageal Function and Reflux Evaluations in Lung Transplantation: A Nationwide Survey of UNOS-Accredited Transplant Centers in the United States.

INTRODUCTION: Gastroesophageal reflux disease has been associated with worse lung transplant outcomes. We aimed to assess local practices for esophageal function testing (EFT) across transplant centers. METHODS: This was a survey study of all United Network for Organ Sharing-accredited adult lung transplant centers regarding local EFT practice. RESULTS: Among 39/63 (60%) responded centers, 38.5% required any EFT (35.9% esophageal manometry, 15.4% pH monitoring, and 28.2% pH impedance), while another 28.2% may consider EFT based on symptoms. Five-year transplant volume was higher among centers requiring EFT (253 vs 159, P = 0.04). DISCUSSION: Only a minority of lung transplant centers routinely obtained EFT, supporting the need for guidelines for standardized reflux/esophageal assessment.

Adverse Outcomes Associated With Atrial Arrhythmias After Veno-Venous Extracorporeal Membrane Oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) is used as a treatment modality in those who fail to respond to conventional care. Hypoxia and medications used in the intensive care unit may increase risk for atrial arrhythmias (AA). This study aims to evaluate the impact of AA on post-VV ECMO outcome. A retrospective review of patients who were placed on VV ECMO between October 2016 and October 2021. One hundred forty-five patients were divided into two groups, AA and no AA. Baseline characteristic and potential risk factors were assessed. Uni- and multivariate analysis using logistic regression models were constructed to evaluate the predictors of mortality between groups. Survival between groups was estimated by the Kaplan-Meier method using the log-rank test. Advanced age with history of coronary artery disease and hypertension were associated with increased risk to develop AA post-VV ECMO placement ( p value < 0.05). Length on ECMO, time intubated, hospital length of stay, and sepsis were significantly increased in patients in the AA group ( p value < 0.05). There was no difference in the overall mortality between the two groups. AAs were associated with worse hospital course and complications but no difference in overall mortality rate. Age and cardiovascular disease seem to be predisposing risk factors for this. Further studies are needed to investigate potential strategies to prevent AAs development in this population.

Evidence of Advanced Pulmonary Vascular Remodeling in Obstructive Hypertrophic Cardiomyopathy With Pulmonary Hypertension.

BACKGROUND: Elevated mean pulmonary artery pressure (mPAP) is common in patients with hypertrophic cardiomyopathy (HCM) and heart failure symptoms. However, dynamic left ventricular (LV) outflow tract obstruction may confound interpretation of pulmonary hypertension (PH) pathophysiologic features in HCM when relying on resting invasive hemodynamic data alone. RESEARCH QUESTION: Do structural changes to the lung vasculature clarify PH pathophysiologic features in patients with HCM with progressive heart failure? STUDY DESIGN AND METHODS: Clinical data and ultrarare lung autopsy specimens were acquired retrospectively from the National Institutes of Health (1975-1992). Patients were included based on the availability of lung tissue and recorded mPAP. Discarded tissue from rejected lung donors served as control specimens. Histomorphology was performed on pulmonary arterioles and veins. Comparisons were calculated using the Student t test and Mann-Whitney U test; Pearson correlation was used to assess association between morphometric measurements and HCM cardiac and hemodynamic measurements. RESULTS: The HCM cohort (n = 7; mean ± SD age, 43 ± 18 years; 71% men) showed maximum mean ± SD LV wall thickness of 25 ± 2.8 mm, mean ± SD outflow tract gradient of 90 ± 30 mm Hg, median mPAP of 25 mm Hg (interquartile range [IQR], 6 mm Hg), median pulmonary artery wedge pressure (PAWP) of 16 mm Hg (IQR, 4 mm Hg), and median pulmonary vascular resistance of 1.8 Wood units (WU; IQR, 2.4 WU). Compared with control samples (n = 5), patients with HCM showed greater indexed pulmonary arterial hypertrophy (20.7 ± 7.2% vs 49.7 ± 12%; P < .001) and arterial wall fibrosis (11.5 ± 3.4 mm vs 21.0 ± 4.7 mm; P < .0001), which correlated with mPAP (r = 0.84; P = .018), PAWP (r = 0.74; P = .05), and LV outflow tract gradient (r = 0.78; P = .035). Compared with control samples, pulmonary vein thickness was increased by 2.9-fold (P = .008) in the HCM group, which correlated with mPAP (r = 0.81; P = .03) and LV outflow tract gradient (r = 0.83; P = .02). INTERPRETATION: To the best of our knowledge, these data demonstrate for the first time that in patients with obstructive HCM, heart failure is associated with pathogenic pulmonary vascular remodeling even when mPAP is elevated only mildly. These observations clarify PH pathophysiologic features in HCM, with future implications for clinical strategies that mitigate outflow tract obstruction.

Limited Effect of Prevention Strategies on Incidence of Clinically Detectable Venous Thromboembolism After Lung Transplantation.

BACKGROUND: Thromboembolic complications are common post-lung transplant, leading to significant morbidity. We instituted multiple interventions because of an observed 36.8% incidence of venous thromboembolism (VTE) (Incidence rate (IR) 5.74/1000 pt days) in our recipients. METHODS: Our initiative commenced January 2015 with enoxaparin initiation within 6-8 hours of intensive care unit arrival and continuation for 4-6 weeks. We evaluated the IR of VTE in lung transplant recipients within 90 days of transplant. In 2017, the protocol was modified to extend the time to initiation of prophylaxis to within 72 hours of ICU arrival. In 2019, we further amended our intraoperative vascular access strategy. RESULTS: Eighteen of 26 lung transplant recipients (LTR) met inclusion criteria in the 2015 cohort. Six of 18 (33.3%) developed VTE, 50% of which were upper extremity (UE), line associated. Fifty two of 75 LTR were eligible for enoxaparin prophylaxis in the 2017 cohort. Fifteen of 52 subjects (28.8%) developed VTE, 77.8% of which were UE and line associated. Despite improved adherence in 2017, there was little change in VTE IR (3.90/1000 pt days compared with 3.85/1000 pt days). Twenty six of 43 LTR met protocol inclusion criteria in the 2019 cohort. Ten subjects (38.5%) developed VTE, 67% of which were UE and line associated (IR 5.18/1000 pt days). CONCLUSION: Our prospective study found that LTR remain at high risk for VTE despite aggressive prophylaxis with 4-6 weeks of enoxaparin and adjustment of vascular access approach. Alternative interventions should be investigated to minimize VTE development in this vulnerable population.

Hemibiotrophic Phytophthora infestans Modulates the Expression of SWEET Genes in Potato (Solanum tuberosum L.).

Sugar Efflux transporters (SWEET) are involved in diverse biological processes of plants. Pathogens have exploited them for nutritional gain and subsequently promote disease progression. Recent studies have implied the involvement of potato SWEET genes in the most devastating late blight disease caused by Phytophthora infestans. Here, we identified and designated 37 putative SWEET genes as StSWEET in potato. We performed detailed in silico analysis, including gene structure, conserved domains, and phylogenetic relationship. Publicly available RNA-seq data was harnessed to retrieve the expression profiles of SWEET genes. The late blight-responsive SWEET genes were identified from the RNA-seq data and then validated using quantitative real-time PCR. The SWEET gene expression was studied along with the biotrophic (SNE1) and necrotrophic (PiNPP1) marker genes of P. infestans. Furthermore, we explored the co-localization of P. infestans resistance loci and SWEET genes. The results indicated that nine transporter genes were responsive to the P. infestans in potato. Among these, six transporters, namely StSWEET10, 12, 18, 27, 29, and 31, showed increased expression after P. infestans inoculation. Interestingly, the observed expression levels aligned with the life cycle of P. infestans, wherein expression of these genes remained upregulated during the biotrophic phase and decreased later on. In contrast, StSWEET13, 14, and 32 didn't show upregulation in inoculated samples suggesting non-targeting by pathogens. This study underscores these transporters as prime P. infestans targets in potato late blight, pivotal in disease progression, and potential candidates for engineering blight-resistant potato genotypes.