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Background. Widespread drug shortages led to higher utilization of ketamine in our intensive care unit, especially among patients with SARS-CoV-2. Objectives. To evaluate the impact of continuous infusion of ketamine on vasopressor requirements in patients with SARS-CoV-2. Method. This was a single-center, retrospective, cohort study comparing mechanically ventilated (MV), adult patients with SARS-CoV-2 receiving either propofol or ketamine for at least 72 hours. Results. 84 patients (mean age of 61-year-old, 68% male) were analyzed. 31 patients received ketamine, and 53 patients received propofol. Mean vasopressor doses were not significantly different between ketamine and propofol groups at prespecified timepoints. However, mean arterial pressures (MAP) were higher in the ketamine group at 24 h, 48 h, and 96 h postsedative initiation. The median opioid infusion requirements were 3 vs. 12.5 mg/hr (p

Izhodišča: Presaditev pljuč je zahtevna metoda zdravljenja za izbrane bolnike z napredovalo pljučno boleznijo. Naraščanje števila primernih kandidatov in standarizacija posega sta v letu 2018 omogočila vzpostavitev transplantacijskega centra v UKC Ljubljana. Prispevek poroča o prvih rezultatih. Metode: Opravili smo analizo lastnega registra bolnikov. Rezultate smo primerjali s skupino bolnikov, ki so jim pred tem opravili presaditev v AKH Dunaj. Rezultati: Med 15. 9. 2018 in 15. 9. 2021 smo opravili 37 presaditev pljuč (od tega pri 13 ženskah). Indikacije so bile KOPB (n = 13, 35 %), pljučne fibroze (n = 7, 19 %), cistična fibroza (n = 5, 14 %), kovidna pljučnica (n = 4, 11 %), bronhiektazije (n = 3, 8 %), pljučna hipertenzija (n = 2, 5 %), limfangioleiomiomatoza (n = 1, 3 %), pomanjkanje alfa-1-antitripsina (n = 1, 3 %) in bronhiolitis (n = 1, 3 %). V primerjavi s prejšnjo skupino bolnikov, napotenih v AKH Dunaj (71 bolnikov, od tega 35 žensk), je bil delež bolnikov s KOPB višji (35 % in 16 %, p = 0,019), bolniki pa so bili starejši (mediana [razpon], 59 [14–68] in 43 [4–58] let, p = 0,001). 76 % darovanih pljuč ni ustrezalo standardnim merilom (30 % darovalcev je bilo starejših od 55 let, 22 % jih je imelo infiltrate na rentgenogramu pljuč, 24 % pa ni izpolnjevalo enega od ostalih meril), v 43 % pa je bila potrebna redukcija velikosti, kar pa ni vplivalo na primarno odpoved presadka. Kratkoročno preživetje je bili podobno v obeh skupinah (1-letno preživetje v UKC Ljubljana 89 % [95 % CI 78–99 %] in v AKH Dunaj 83 % [95 % CI 74–92 %]). Zaključek: Prvi rezultati kažejo, da so zgodnji izidi po presaditvi pljuč primerljivi pri bolnikih, ki so imeli presaditev v UKC Ljubljana ali v AKH Dunaj.

Abstract Purpose The prognostic value of pretreatment and preoperative fibrinogen plasma levels and the modified Glasgow prognostic score (mGPS) in stage III/N2 non-small cell lung cancer (NSCLC) patients who receive neoadjuvant treatment followed by radical surgery is yet unclear. Methods Fibrinogen levels and mGPS of 84 patients with initial stage III/N2 NSCLC, who received neoadjuvant therapy followed by complete surgical resection from 2002 to 2014 were retrospectively analyzed and correlated with clinical parameters and overall survival (OS). Data were analyzed using log-rank and Cox regression analysis adjusted for clinical and pathological factors. Results Median serum fibrinogen level after neoadjuvant treatment was 439 mg/dL (IQR 158 mg/dL). Elevated fibrinogen levels (> 400 mg/dL) after neoadjuvant treatment were significantly associated with poorer OS (28.2 months vs. 60.9 months, HR 0.562, p = 0.048). Importantly, a decrease in fibrinogen levels after neoadjuvant treatment (n = 34) was found to be an independent predictor for favorable OS in multivariate analysis (HR 0.994, p = 0.025). Out of 80 patients, 55, 19 and 6 patients had a mGPS of 0, 1 and 2, respectively. Moreover, elevated mGPS after neoadjuvant treatment (mGPS 1–2) showed a non-significant trend for poorer OS compared to mGPS 0 (28.2 vs. 46.5 months, HR 0.587, p = 0.066). Conclusion Elevated fibrinogen levels after neoadjuvant therapy prior to surgery in stage III/N2 NSCLC patients are associated with significant disadvantage for OS. A decrease in fibrinogen levels after neoadjuvant therapy was found to be a predictor for superior OS in this retrospective patient cohort.

Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is successfully treatable with pulmonary endarterectomy (PEA), balloon pulmonary angioplasty, and medical therapy. Registry to Evaluate Early and Long‐Term Pulmonary Arterial Hypertension Disease Management risk score (RRS) is able to predict long‐term outcome in inoperable patients or in patients with residual PH after surgery. We performed a post hoc analysis of RRS in patients who were enrolled in the CTREPH study (NCT01416636), a randomized, double‐blind clinical trial comparing high‐dose and low‐dose subcutaneous (SC) treprostinil in patients with severe CTEPH that was classified by an interdisciplinary CTEPH team as nonoperable, or as persistent or recurrent pulmonary hypertension after PEA. Baseline mean RRS was similar in both treatment groups (8.7 in high‐dose arm vs. 8.6 in low‐dose arm), but mean RRS change from baseline to Week 24 was greater in the high‐dose treprostinil group than in the low‐dose treprostinil group (−0.88 vs. −0.17). The difference in RRS change from baseline to Week 24 between high dose versus low dose was statistically significant with mean difference of −0.70 (95% confidence interval: −1.36 to −0.05, p = 0.0352), and was driven mainly by improvement of World Health Organization functional class and N‐terminal pro‐brain natriuretic peptide concentration. SC treprostinil therapy administered in standard dose had positive effect on the risk profile measured by RRS in patients with inoperable or persistent/recurrent severe CTEPH. Although our study was limited by the small sample size and post hoc nature, assessment of risk profile is of great importance to this particular patient population with very poor prognosis.

Background: Modern distal biceps reconstruction techniques generally have satisfactory outcomes, but are not without complications. Posterior interosseous nerve (PIN) palsy is a rare but potentially devastating complication of bicortical metal button fixation. Recently, a unicortical, intramedullary, repair technique utilizing a suture anchor has been described. The primary aim of this study was to compare short-term functional and patient-reported outcomes and complication rates in patients receiving unicortical intramedullary repair (UR) with suture anchor against those receiving bicortical repair (BR) with metallic button. We hypothesized that UR would have equally satisfactory outcomes without the complication profile. Methods: Retrospective chart review was conducted for all patients undergoing operative fixation of distal biceps tendon ruptures from 2015 to 2021 at our tertiary referral center. Twenty patients received BR, and eight patients received UR. Patient demographics and surgical complications were compared. QuickDASH scores at two-month and latest in-person and telehealth postoperative visits, as well as elbow and forearm range of motion at last clinical visit, were collected and analyzed. Results: Average patient age in the BR & UR cohorts were 49.3 ± 9.3 and 42.1 ± 6.2 years, respectively, with a male predominance. There was no statistical difference in patient age, sex, hand dominance, injury laterality, injury chronicity, and follow-up duration. Range of motion was comparable and excellent in both groups. Latest follow-up was 3.0 ± 0.5 years in the BR and 1.5 ± 0.4 years in the UR cohorts. QuickDASH scores improved between the two-month and latest time points in each cohort however did not differ significantly in head-to-head comparison. Complications included a case of PIN palsy, distal biceps tendon rerupture, and lateral antebrachial cutaneous nerve (LABC) neuropraxia in the BR group and two cases of LABC neuropraxia in the UR group. The number needed to treat (NNT) for the prevention of one additional case of PIN palsy using UR is 22 patients. Discussion: Short-term functional and patient-reported outcomes in traditional BR and newly reported UR of distal biceps tendon ruptures are comparable and excellent. UR did not have higher failure rate despite follow-up periods beyond what is typically reported for tendon reruptures. In this limited retrospective cohort study, UR also did not encounter postoperative PIN palsy and had an NNT of 22 patients. In the appropriate clinical setting, this provides early evidence supporting the utilization of unicortical intramedullary suture anchor fixation of distal biceps tendon ruptures as well as associated perioperative interventions such as preoperative nerve blocks.

Objectives: The ratio of pulmonary artery (PA) and ascending aorta (AA) diameters has recently been shown to be a useful indicator for disease severity and predictor of outcome in patients with pulmonary hypertension and heart failure. This study aimed at evaluating the applicability of this ratio for perioperative risk assessment of patients with chronic thromboembolic pulmonary hypertension undergoing pulmonary endarterectomy. Methods: In this retrospective cohort study on 149 patients undergoing pulmonary endarterectomy between 2013 and 2020, the preoperative PA to AA ratio was analyzed on axial computed tomography. Variables of pulmonary hemodynamic status were assessed during preoperative right heart catheterization and postoperative Swan-Ganz catheter measurements. Perioperative survival was analyzed by Kaplan-Meier method and log-rank tests. Results: Preoperative computed tomography measurements showed a median AA diameter of 31 mm (range, 19-47 mm), and a median PA diameter of 36 mm (range, 25-55 mm). The calculated median PA to AA ratio was 1.13 (range, 0.79-1.80). PA to AA ratio correlated positively with PA pressure (systolic, r = 0.352 [P 1.136; survival probability, 88.9%). Conclusions: PA to AA ratio shows a correlation with other variables associated with pulmonary hypertension. In addition, patients with higher PA to AA ratios have lower survival probabilities after PEA. Further analysis of PA to AA ratio on the selection of chronic thromboembolic pulmonary hypertension for different treatment modalities—pulmonary endarterectomy, medical therapy, and or balloon pulmonary angioplasty—is warranted.

Background: NT-proBNP and GDF-15 are established blood-derived biomarkers for risk assessment in pulmonary hypertension (PH), despite limited sensitivity and specificity. Apelin has a crucial function in endothelial homeostasis, thus it might represent a new biomarker for PH. However, there are numerous circulating apelin isoforms, and their potential role in this setting is unknown. This study evaluated different apelin isoforms in PH patients and prospectively evaluated the role of apelin-17 in comparison with NT-proBNP and GDF-15 as diagnostic marker in idiopathic pulmonary arterial hypertension (IPAH).Methods: Based on our pilot study, we performed a power calculation for apelin-13, apelin-17, apelin-36, as predictor of IPAH vs healthy controls. Apelin-17 provided the best discriminatory power, and accordingly, we enrolled n = 31 patients with IPAH and n = 31 matched healthy controls in a prospective study. NT-proBNP and GDF-15 was determined in all patients. ROC curve analysis was performed to assess the diagnostic value of the markers and their combinations.Results: Apelin-17, NT-proBNP, and GDF-15 were significantly elevated in IPAH patients as compared to controls (p < .001). Apelin-17 detected IPAH with a sensitivity of 68% and a specificity of 93% at a cut-off value of >1,480 pg/ml (AUC 0.86, 95%CI:0.76–0.95) as compared to GDF-15 (sensitivity 86%; specificity 72%, AUC 0.81 (95%CI:0.7–0.92)) and NT-proBNP (sensitivity 86%; specificity 72% (AUC 0.85, 95%CI:0.75–0.95)). Combinations of these markers could be used to increase either specificity or sensitivity.Conclusion: Apelin-17 appears to be suitable blood derived diagnostic marker for idiopathic pulmonary arterial hypertension.

Objective: A small but relevant proportion of patients with cystic fibrosis develop severely asymmetric chest cavities during the course of their disease. For these patients, the best surgical approach for lung transplantation (LTx) and optimal size matching strategies are controversial. Methods: All cystic fibrosis patients with asymmetric chest cavities who underwent LTx at the Medical University of Vienna between 2003 and 2017 were identified (n = 13). Patients were grouped according to different surgical strategies: unilateral full-size and contralateral lobar transplantation (n = 4), standard double LTx after mobilization/repositioning of the mediastinum (n = 3), oversized single LTx followed by pneumonectomy on the smaller contralateral side (n = 4), and single LTx after a remote contralateral pneumonectomy (n = 2). Results: Compared with cystic fibrosis patients with symmetric chests (n = 276, control group), the perioperative management of patients with asymmetric chests was often more complicated. Consequently, 90-day mortality was heightened (23.1% vs 6.5%). Despite this, long-term survival was good with a 5-year survival rate of 69% compared with 78%. Of note, outcome seemed superior for patients who surgery was undertaken with a bilateral compared with a unilateral approach. Conclusions: Severely asymmetric chest cavities present challenges in regard to the surgical strategy, size matching, and postoperative management. However, in carefully selected patients, LTx provides an adequate long-term outcome.

A central feature of progressive vascular remodeling is altered smooth muscle cell (SMC) homeostasis; however, the understanding of how different cell populations contribute to this process is limited. Here, we utilized single-cell RNA sequencing to provide insight into cellular composition changes within isolated pulmonary arteries (PAs) from pulmonary arterial hypertension and donor lungs. Our results revealed that remodeling skewed the balanced communication network between immune and structural cells, in particular SMCs. Comparative analysis with murine PAs showed that human PAs harbored heterogeneous SMC populations with an abundant intermediary cluster displaying a gradient transition between SMCs and adventitial fibroblasts. Transcriptionally distinct SMC populations were enriched in specific biological processes and could be differentiated into 4 major clusters: oxygen sensing (enriched in pericytes), contractile, synthetic, and fibroblast-like. End-stage remodeling was associated with phenotypic shift of preexisting SMC populations and accumulation of synthetic SMCs in neointima. Distinctly regulated genes in clusters built nonredundant regulatory hubs encompassing stress response and differentiation regulators. The current study provides a blueprint of cellular and molecular changes on a single-cell level that are defining the pathological vascular remodeling process.

The rising global HIV-1 burden urgently requires vaccines capable of providing heterologous protection. Here, we developed a clade C HIV-1 vaccine consisting of priming with modified vaccinia Ankara (MVA) and boosting with cyclically permuted trimeric gp120 (CycP-gp120) protein, delivered either orally using a needle-free injector or through parenteral injection. We tested protective efficacy of the vaccine against intrarectal challenges with a pathogenic heterologous clade C SHIV infection in rhesus macaques. Both routes of vaccination induced a strong envelope-specific IgG in serum and rectal secretions directed against V1V2 scaffolds from a global panel of viruses with polyfunctional activities. Envelope-specific IgG showed lower fucosylation compared with total IgG at baseline, and most of the vaccine-induced proliferating blood CD4 + T cells did not express CCR5 and α4β7, markers associated with HIV target cells. After SHIV challenge, both routes of vaccination conferred significant and equivalent protection, with 40% of animals remaining uninfected at the end of six weekly repeated challenges with an estimated efficacy of 68% per exposure. Induction of envelope-specific IgG correlated positively with G1FB glycosylation, and G2S2F glycosylation correlated negatively with protection. Vaccine-induced TNF-α + IFN-γ + CD8 + T cells and TNF-α + CD4 + T cells expressing low levels of CCR5 in the rectum at prechallenge were associated with decreased risk of SHIV acquisition. These results demonstrate that the clade C MVA/CycP-gp120 vaccine provides heterologous protection against a tier2 SHIV rectal challenge by inducing a polyfunctional antibody response with distinct Fc glycosylation profile, as well as cytotoxic CD8 T cell response and CCR5-negative T helper response in the rectum.