Alemtuzumab treatment for multiple sclerosis in Austria: An observational long-term outcome study.

BACKGROUND/OBJECTIVE: Observational real-world study to analyze the clinical effects of alemtuzumab (ALEM) and subsequent disease-modifying therapy (DMT) usage in multiple sclerosis (MS). METHODS: Data retrieved from the Austrian MS treatment registry (AMSTR) included baseline (BL) characteristics (at ALEM start), annualized relapse rate (ARR), 6-month confirmed progression independent of relapse activity (PIRA; ≥ 0.5-point Expanded Disability Status Scale (EDSS) score increase), 6-month confirmed disability improvement (CDI; ≥ 0.5-point EDSS decrease), and safety outcomes until initiation of a subsequent DMT. The EDSS was re-baselined at 30 days from ALEM start (BL EDSS). RESULTS: Eighty-seven ALEM-treated patients (median age: 32 years, 72% female, 14% treatment-naïve) were followed for a median of 55 (interquartile range 31-68) months. We found significant reductions in the ARR from 1.16 before ALEM to 0.15 throughout Years 1-9 (p < 0.001). Subsequent DMTs were initiated in 19 patients (22%, 74% anti-CD20 monoclonal antibodies). At Year 5 (n = 53), more patients achieved CDI (58%, 95% confidence interval (CI) 45%-71%) than had experienced PIRA (14%, CI 7.5%-24%), and 58% remained relapse-free. Shorter MS duration (p < 0.001, hazard ratio (HR) 0.86 (CI 0.80-0.93)) and no previous high-efficacy treatment (p < 0.001, HR 5.16 (CI 2.66-10.0)) were the best predictors of CDI, while PIRA was associated with a higher number of previous DMTs (p = 0.04, HR 3.06, CI 1.05-8.89). We found no new safety signals. INTERPRETATION: ALEM had long-lasting beneficial effects on the ARR and disability improvement, especially when initiated early in the course of the disease. Only a subset of patients received subsequent DMTs.

Alternative vein bypass in octogenarians with chronic limb-threatening ischaemia.

BACKGROUND: Octogenarians are regarded as one of the frailest patient groups among the chronic limb-threatening ischaemia population with high perioperative morbidity and mortality rates. As a result, alternative vein bypass surgery in the absence of sufficient great saphenous vein is often not considered as a potential treatment option. The aim of this study was to compare the results of octogenarians undergoing alternative vein bypass surgery due to chronic limb-threatening ischaemia to younger patients. METHODS: A single-centre retrospective analysis of patients undergoing bypass surgery for chronic limb-threatening ischaemia with alternative autologous vein grafts between 1997 and 2018 was performed. Patients aged over 80 years were compared with those under 80 years. Graft patency rates were assessed and a risk factor analysis for limb loss was performed. RESULTS: In total, 592 patients underwent bypass surgery during the study interval. Twenty-one per cent (n = 126) of patients were 80 years or older. At 4 years, primary, primary-assisted and secondary patency as well as limb salvage rates were not significantly different between the two groups (46% versus 50%, 60% versus 66%, 69% versus 72%, 72% versus 77%, for octogenarians versus non-octogenarians respectively). Major amputations were performed in 27 (21%) octogenarians and 91 (20%) non-octogenarians (P = 0.190). No higher 30-day and long-term mortality rates nor morbidity rates were detected in the octogenarian group with a median follow-up time of 27 (interquartile range 12-56) months. Minor amputation, the reason for alternative vein grafts, as well as the profunda femoris artery as proximal origin of the bypass were risk factors for limb loss in the postoperative course. CONCLUSION: Alternative vein bypass surgery in octogenarians with chronic limb-threatening ischaemia is safe and effective in terms of patency rates, limb salvage and survival compared with younger patients in the absence of sufficient great saphenous vein. Age alone should not be a deterrent from performing bypass surgery.

Isolated or Combined Ascending Aortic Replacement through a Partial Sternotomy: Early and Midterm Outcomes.

BACKGROUND: We aimed to investigate the in-hospital and midterm outcomes of patients undergoing ascending aortic replacement (AAR) through a partial or a full sternotomy approach through a propensity matching analysis. METHODS: We retrospectively included all patients (n = 167) who underwent elective AAR in our institution between 2013 and 2020. The study population was divided into two groups according to the surgical access (40 patient in the partial sternotomy or "PS" group and 127 in the full sternotomy or "FS" group). Due to the significant differences between the groups, a propensity matching of 1:3 was applied. In-hospital complications, survival, and reoperation at follow-up were investigated. RESULTS: The PS group showed higher cross-clamp and cardiopulmonary bypass times than the FS group (94.2 vs. 83 minutes and 164.2 vs. 126.8 minutes, respectively). Moreover, the postoperative ventilation time was significantly higher in the PS group, but it did not affect the length of stay in the intensive care unit (ICU). The incidences of bleeding, stroke, and mortality were comparable between the two groups (11 vs. 3%, 3 vs. 6%, and 5 vs. 3%, respectively). After a median follow-up of 2 ± 1.98 years, the Kaplan-Meier analysis showed no significant differences between the two groups (log-rank, p = 0.17) in terms of survival. CONCLUSION: The surgical ascending aorta replacement through a partial sternotomy is associated with longer operative times, but this does not affect the early as well as the long-term follow-up.

Glow up: does a professional photoshoot intervention affect self-esteem and emotions among adolescent psychiatric patients?-A longitudinal intervention study.

Background: Today, online communication is shaped by a billion-dollar social media (SM) and social networking site (SNS) industry. Visual content consumed by children and adolescents has been shown to influence behavioral patterns, state emotions, and self-esteem (SE). In this study, we introduced a novel intervention creating visual content through a professional photoshoot and investigated its impact on state emotions and SE in child and adolescent psychiatric (CAP) patients. Methods: Standardized and validated self-rating questionnaires were used to assess SE, state emotions, coping mechanisms, psychopathological symptoms, and internet use behavior at baseline. SE and state emotions were monitored at different time points around a professional photoshoot within 45 CAP patients (30 female patients; mean age, 15.1 years) using a longitudinal design. Results: Within-subject repeated-measures ANOVA and bootstrapped paired-sample t-tests showed a significant fluctuation in state emotions and SE throughout the intervention. Spearman correlations and univariate logistic regressions revealed that internalizing symptomatology and maladaptive coping significantly worsened the outcome of the intervention on state emotions and SE in girls. Internet-related variables heightened the positive effect of the intervention in boys and lowered SE in girls during the intervention. Conclusion: The photo intervention had various gender-specific effects. Boys did benefit from the intervention in terms of longitudinal outcome on positive state emotions (PE) and SE, even positively influenced by SNS and SM. Thus, it might be concluded that online social comparison was processed more beneficial in boys. In contrast, when working with visual content in girls, psychopathology and coping must be considered. Internet consumption in general, especially SM and SNS, was related to low SE in girls. Nevertheless, when therapeutically accompanied, the "glow up moment" during the shoot (high on PE and SE; low on negative state emotions) could be used as an index moment for therapeutic reflection.

Mid-term surgical success after transscleral ab interno glaucoma gel stent implantation.

PURPOSE: To investigate the surgical success and efficacy of XEN45 implantation (XEN45 µm, AbbVie Inc., USA) with and without combined cataract surgery up to the first 5 years. METHODS: In a prospective observational monocentric trial, 192 eyes of 157 patients with open-angle glaucoma received either XEN45 implants only (solo surgery group) or combined surgery/cataract surgeries (combined surgery group). Surgical success (qualified and full success; IOP-limit: ≤12, 15, 18, 21 mmHg), time to secondary IOP-lowering procedure, IOP and number of IOP-lowering medications were analysed for 1, 2, 3, 4 and 5 years. RESULTS: Compared to baseline, IOP (24.1 ± 8.1 to 12.6 ± 2.8 mmHg, -48%, p < 0.001) and the number of IOP-lowering medications (3.0 ± 1.0 to 1.5 ± 1.2, -50%, p < 0.001) decreased significantly at 5 years. Although no differences between IOP and the number of IOP-lowering medication courses between the groups were detected at 5 years (p > 0.11), the combined procedure (63%, 37%) showed better success rates compared to the solo procedure (36%, 13%) in the definition IOP ≤18 and ≤12 mmHg (p = 0.035, 0.028). Solo XEN45 procedures had a higher rate of secondary IOP-lowering procedures compared to combined XEN45 cataract procedures (hazard ratio: 2.02, 95%CI: 1.03-3.97, p = 0.04). Twenty per cent of the eyes, including both procedures, required a secondary IOP-lowering procedure within 5 years. CONCLUSIONS: The XEN45 implant is effective in lowering IOP and the number of IOP-lowering medications in patients with open-angle glaucoma in the mid-term. Comparing XEN45 implant results with the results of trabeculectomy available in current literature, we speculate that there might be a higher surgical success rate without medications in favour of trabeculectomy.

Impaired Sleep in Patients with Post-COVID-19 Syndrome Compared to Healthy Controls: A Cross-Sectional Trial.

INTRODUCTION: To objectify self-reported sleep disorders in individuals with post-COVID-syndrome (PCS), we aimed to investigate the prevalence and nature of sleep disturbances by polysomnography (PSG) in PCS compared to healthy individuals. METHODS: People with PCS (n = 21) and healthy controls (CON, n = 10) were included in this prospective trial. At baseline, clinical and social anamnesis, lung function, 1 min sit-to-stand test (STST) and Pittsburgh Sleep Quality Index (PSQI) were assessed. For a single-night, sleep health was evaluated by video-PSG. The apnoea/hypopnea index (AHI) was used as the primary outcome. RESULTS: Twenty patients with PCS (50 ± 11 y, BMI 27.1 m2/kg, SARS-CoV-2 infection 8.5 ± 4.5 months ago) and 10 CON participants (46 ± 10 y, BMI 23.0 m2/kg, no SARS-CoV-2 infection in the history) completed the study. Forced vital capacity (p = 0.018), STST repetitions (p < 0.001), and symptoms of dyspnoea (at rest: p = 0.002, exertion: p < 0.001) were worse in PCS compared to CON. PSQI score (PCS: 7.5 ± 4.7 points) was higher in PCS compared to CON (Δ = 3.7 points, 95% CI [0.4-7.1] p = 0.015), indicating poor sleep in 80% of patients with PCS. Although PSG showed comparable sleep stage distributions in both groups, AHI (Δ = 9.0 n/h, 95% CI [3.3-14.8], p = 0.002), PLM index (Δ = 5.1 n/h, 95% CI [0.4-9.8], p = 0.017), and the prevalence of sleep apnoea (60% vs. 10%, p = 0.028) was significantly higher in PCS compared to CON. CONCLUSION: Quantifiable subjective limitations of sleep have been revealed by PSG data in this PCS cohort. More than half of PCS patients had signs of sleep apnoea, highlighting the importance of sleep screening in PCS.

Using Isolated Femoral Bifurcation Endarterectomy or Combined with Bypass Surgery for Patients with Chronic Limb-Threatening Ischemia.

Background and Objectives: The aim of this study was to evaluate the clinical outcomes of patients suffering from chronic limb-threatening ischemia (CLTI) and tissue loss treated with primary isolated femoral bifurcation endarterectomy (FBE) or with FBE combined with bypass surgery. Materials and Methods: This retrospective study was performed in a tertiary university-based care centre. Between January 2008 and December 2019, a prospectively collected database of patients suffering from CLTI and tissue loss and undergoing either primary FBE (group A) or FBE in combination with bypass surgery (group B) was analysed. Study endpoints were ulcer healing, primary and secondary patency rate, limb salvage, and survival. Results: In total, FBE was performed in 73 patients and FBE with bypass in 60 patients. Between both groups, there were no significant differences regarding demographic data or the Global Limb Anatomic Staging System (GLASS) grade III and IV of femoropopliteal lesions. After 3 years, ulcer healing could be achieved in 72% of FBE and in 75% of FBE with bypass patients. The primary patency rate was 95% and 91% for FBE and 83% and 80% for FBE with bypass after one and three years, respectively. The 3-year limb-salvage rate was 78% for FBE and 84% for FBE with bypass. The secondary patency rate after one and three years was 99% and 97% for FBE and 93% and 88% for FBE with bypass. Conclusions: FBE and FBE with bypass are equally effective for ulcer healing in cases of combined CFA and superficial femoral artery lesions. There was no significant difference between both groups regarding primary and secondary patency rates, limb salvage rates and ulcer healing. Isolated FBE could be an alternative strategy in patients with higher operative risk.

Exploring the Impact of TLR-2 Signaling on miRNA Dysregulation in Intervertebral Disc Degeneration.

Toll-like receptors (TLRs) are key mediators of inflammation in intervertebral disc (IVD) degeneration. TLR-2 activation contributes to the degenerative process by increasing the expression of extracellular matrix-degrading enzymes, pro-inflammatory cytokines, and neurotrophins. As potent post-transcriptional regulators, microRNAs can modulate intracellular mechanisms, and their dysregulation is known to contribute to numerous pathologies. This study aims to investigate the impact of TLR-2 signaling on miRNA dysregulation in the context of IVD degeneration. Small-RNA sequencing of degenerated IVD cells shows the dysregulation of ten miRNAs following TLR-2 activation by PAM2CSK4. The miR-155-5p is most significantly upregulated in degenerated and non-degenerated annulus fibrosus and nucleus pulposus cells. Sequence-based target and pathway prediction shows the involvement of miR-155-5p in inflammation- and cell fate-related pathways and TLR-2-induced miR-155-5p expression leads to the downregulation of its target c-FOS. Furthermore, changes specific to the activation of TLR-2 through fragmented fibronectin are seen in miR-484 and miR-487. Lastly, miR-100-3p, miR-320b, and miR-181a-3p expression exhibit degeneration-dependent changes. These results show that TLR-2 signaling leads to the dysregulation of miRNAs in IVD cells as well as their possible downstream effects on inflammation and degeneration. The identified miRNAs provide important opportunities as potential therapeutic targets for IVD degeneration and low back pain.

Repeated iv anti-CD20 treatment in multiple sclerosis: Long-term effects on peripheral immune cell subsets.

OBJECTIVE: Repeated intravenous administration of anti-CD20 depleting monoclonal antibodies 6 months apart is among the highly effective treatment options in multiple sclerosis (MS). Here, we aimed to investigate peripheral immune cell subset depletion kinetics following either rituximab (RTX) or ocrelizumab (OCR) infusions in people with MS (pwMS). METHODS: We studied pwMS treated de-novo with either RTX (n = 7) or OCR (n = 8). The examinations were scheduled before the initiation of anti-CD20 therapy and every 12 weeks for up to 15 months. Immunophenotyping of immune cell subsets in peripheral blood was performed by multiparametric fluorescence cytometry. RESULTS: A significant, persistent decrease of CD19+ B cells was observed already with the first anti-CD20 infusion (p < 0.0001). A significant proportional reduction of memory B cells within the B-cell pool was achieved only after two treatment cycles (p = 0.005). We observed a proportional increase of immature (p = 0.04) and naive B cells (p = 0.004), again only after the second treatment cycle. As for the peripheral T-cell pool, we observed a continuous proportional increase of memory T helper (TH) cells/central memory TH cells (p = 0.02/p = 0.008), while the number of regulatory T cells (Treg) decreased (p = 0.007). The percentage of B-cell dependent TH17.1 central memory cells dropped after the second treatment cycle (p = 0.02). No significant differences in the depletion kinetics between RTX and OCR were found. INTERPRETATION: Peripheral immune cell profiling revealed more differentiated insights into the prompt and delayed immunological effects of repeated intravenous anti-CD20 treatment. The observation of proportional changes of some pathogenetically relevant immune cell subsets only after two infusion cycles deserves further attention.

Patient-Reported Outcomes Following Breast Reconstruction With the Transverse Myocutaneous Gracilis Flap Using the BREAST-Q and Lower Extremity Function Scale.

BACKGROUND: The transverse myocutaneous gracilis (TMG) flap is a viable and safe option for breast reconstruction in patients with limited abdominal tissue or other contraindications for abdominal-based flaps. Although it is one of the most common flaps employed for breast reconstruction, data on patient-reported outcomes is limited. OBJECTIVES: The authors seek to evaluate patient satisfaction and aesthetic outcome after breast reconstruction with the TMG flap. METHODS: All patients who underwent breast reconstruction with a TMG flap between March 2010 and October 2020 were identified. Invitation to a digital version of the BREAST-Q reconstructive module and the Lower Extremity Function Scale (LEFS) was sent to 105 patients. Patient demographics, complications, and surgical details were collected and retrospectively analyzed. BREAST-Q and LEFS scores were calculated and compared to the literature. RESULTS: Eighty-two patients participated in the study. Median follow-up was 5.9 years, with a mean patient age of 45.7 years. Most patients (90.2%) received treatment due to previous cancer of the breast, and 17.1% underwent immediate reconstruction. The mean score for "Satisfaction with Breast" was 66/100. Postoperative lower extremity function was high, with a median LEFS score of 78/80. A LEFS score below the median value was found to be significantly associated with active smoking (P = .049). Patients also reported high satisfaction with donor sites (8/11). CONCLUSIONS: Patient satisfaction and aesthetic outcome after breast reconstruction with TMG flaps is high and comparable to other common techniques. Lower extremity function is not impaired after flap harvest.

High-intensity non-invasive ventilation during exercise-training versus without in people with very severe COPD and chronic hypercapnic respiratory failure: a randomised controlled trial.

BACKGROUND: People with very severe chronic obstructive pulmonary disease (COPD) using nocturnal non-invasive ventilation (NIV) for chronic hypercapnic respiratory failure (CHRF) experience reduced exercise capacity and severe dyspnoea during exercise training (ET). The use of NIV during ET can personalise training during pulmonary rehabilitation (PR) but whether high-intensity NIV (HI-NIV) during exercise is accepted and improves outcomes in these extremely physically limited patients is unknown. The aim of this trial was to determine if ET with HI-NIV during PR was more effective than without at improving exercise capacity and reducing dyspnoea during exercise. METHODS: Patients with COPD, CHRF and nocturnal-NIV were randomised to supervised cycle-ET as part of PR with HI-NIV or without (control). Primary outcome was change in cycle endurance time (ΔCETtime), while secondary outcomes were dyspnoea at isotime during the cycle endurance test and during ET-sessions and for the HI-NIV group, post-trial preferred exercising method. RESULTS: Twenty-six participants (forced expiratory volume in 1 s 22±7%pred, PaCO251±7 mm Hg) completed the trial (HI-NIV: n=13, ET: IPAP 26±3/EPAP 6±1 cm H2O; control n=13). At completion of a 3 week ET-programme, no significant between-group differences in ΔCETtime were seen (HI-NIV-control: Δ105 s 95% CI (-92 to 302), p=0.608). Within-group ΔCETtime was significant (HI-NIV: +246 s 95% CI (61 to 432); control: +141 s 95% CI (60 to 222); all p<0.05). The number of responders (Δ>minimal important difference (MID)101 s: n=53.8%) was the same in both groups for absolute ΔCETtime and 69.2% of control and 76.9% of the HI-NIV group had a %change>MID33%.Compared with control, the HI-NIV group reported less isotime dyspnoea (Δ-2.0 pts. 95% CI (-3.2 to -0.8), p=0.005) and during ET (Δ-3.2 pts. 95% CI (-4.6 to -1.9), p<0.001). Most of the HI-NIV group (n=12/13) preferred exercising with NIV. CONCLUSION: In this small group of patients with very severe COPD requiring nocturnal NIV, participation in an ET-programme during PR significantly improved exercise capacity irrespective of HI-NIV use. Reported dyspnoea was in favour of HI-NIV. TRIAL REGISTRATION NUMBER: NCT03803358.

HER2 copy number determination in breast cancer using the highly sensitive droplet digital PCR method.

Human epidermal growth factor receptor 2 (HER)-positive breast cancer (BC) is characterized by an aggressive clinical course. In the case of HER2 overexpression/amplification, patients benefit from HER2-targeting therapies. Standardized diagnostic HER2 assessment includes immunohistochemistry (IHC) and/or in situ hybridization (ISH). The aim of this study was to compare this "gold standard" with the Droplet Digital™ polymerase chain reaction (ddPCR), a method that allows sensitive and precise detection of copy number variations (CNV) in FFPE (formalin-fixed, paraffin-embedded) DNA samples. Partitioning of the PCR reaction into 20,000 droplets enables a precise quantitative "CN" discrimination also in heterogeneous samples. FFPE breast cancer samples (n = 170) with routinely assessed HER2 status by IHC/ISH were retrospectively analyzed using the ddPCR CNV ERBB2 assay. Comparison of HER2 status assessment by the two methods revealed concordant results in 92.9% (158/170) of the cases. Discrepant cases were verified and interpreted. For ddPCR, a cut off value of 3 HER2 copies was set to distinguish between HER2-negative and HER2-positive BC. Results obtained with the ddPCR CNV ERBB2 assay were consistent and reproducible, and serial dilutions demonstrated a high stability and sensitivity of the method. The ddPCR CNV ERBB2 assay may be a specific and convenient tool to quantify HER2 copy numbers in BC samples. In our study, this method showed high reproducibility in accuracy of HER2 assessment compared to IHC/ISH analysis.

Mentalizing in first-time fathers: reflective functioning as a mediator between attachment representation and sensitivity.

Sensitivity in parent-child interaction is essential for child development. Since fathers are increasingly involved in childrearing, identifying factors leading to paternal sensitivity is crucial. We examined the relation between attachment representation and reflective functioning (RF) as factors influencing paternal sensitivity in a longitudinal study including N = 40 first-time fathers (Mage = 33) and their 6-month-old children. We used the Adult Attachment Interview during pregnancy to assess paternal attachment representation and general RF, the Parental Development Interview to assess fathers' parental RF, and the Emotional Availability Scale to measure sensitivity at child's age of 6 month. Data show that secure paternal attachment representation, high general and parental RF are associated with higher levels of paternal sensitivity. Further, parental RF mediates the association between attachment representation and paternal sensitivity. These findings contribute to the identification of a causal interplay in that they suggest an explanatory effect of RF on the association between fathers' attachment representation, and sensitivity.

A Machine Learning Model for the Accurate Prediction of 1-Year Survival in TAVI Patients: A Retrospective Observational Cohort Study.

BACKGROUND: predicting the 1-year survival of patients undergoing transcatheter aortic valve implantation (TAVI) is indispensable for managing safe early discharge strategies and resource optimization. METHODS: Routinely acquired data (134 variables) were used from 629 patients, who underwent transfemoral TAVI from 2012 up to 2018. Support vector machines, neuronal networks, random forests, nearest neighbour and Bayes models were used with new, previously unseen patients to predict 1-year mortality in TAVI patients. A genetic variable selection algorithm identified a set of predictor variables with high predictive power. RESULTS: Univariate analyses revealed 19 variables (clinical, laboratory, echocardiographic, computed tomographic and ECG) that significantly influence 1-year survival. Before applying the reject option, the model performances in terms of negative predictive value (NPV) and positive predictive value (PPV) were similar between all models. After applying the reject option, the random forest model identified a subcohort showing a negative predictive value of 96% (positive predictive value = 92%, accuracy = 96%). CONCLUSIONS: Our model can predict the 1-year survival with very high negative and sufficiently high positive predictive value, with very high accuracy. The "reject option" allows a high performance and harmonic integration of machine learning in the clinical decision process.

Clinical and demographic factors affecting trough levels of isavuconazole in critically ill patients with or without COVID-19.

BACKGROUND: The broad-spectrum antifungal isavuconazole is administered to treat invasive aspergillosis and mucormycosis. OBJECTIVES: Isavuconazole plasma concentrations in critically ill ICU patients with or without COVID-19 and invasive fungal infection were determined, and factors for sub-therapeutic drug levels (<1 µg/mL) were evaluated. PATIENTS AND METHODS: Isavuconazole plasma levels were measured as part of therapeutic drug monitoring (TDM) in ICUs of a tertiary hospital. Concentrations determined 20-28 h after previous dosing were defined as trough (Cmin ) levels. A total of 160 Cmin levels from 62 patients with invasive fungal infections were analysed, 30 of which suffering from COVID-19. Patient characteristics included into univariable and multivariable analyses were gender, age, COVID-19 status, body mass index (BMI), sepsis-related organ failure (SOFA) score, renal replacement therapy (RRT) and extracorporeal membrane oxygenation (ECMO) requirement. RESULTS: The mean Cmin of isavuconazole in all patients was 1.64 µg/mL (interquartile range 0.83-2.24 µg/mL, total range 0.24-5.67 µg/mL). In total, 34.4% of the Cmin values (corresponding to 46.8% of patients) were below a threshold concentration of 1 µg/mL. Drug concentrations between patients with or without COVID-19 did not differ (p = .43). In contrast, levels were significantly lower in patients with female sex (p = .0007), age ≤ 65 years (p = .002), BMI > 25 (p = .006), SOFA score > 12 (p = .026), RRT (p = .017) and ECMO requirement (p = .001). CONCLUSIONS: Isavuconazole plasma levels can be negatively affected by patients' risk factors, supportive renal replacement and ECMO therapy. Future prospective studies analysing the relevance of isavuconazole drug levels in ICU patient outcome are urgently needed.

Short-term outcomes and costs analysis of robotic-assisted versus laparoscopic cholecystectomy-a retrospective single-center analysis.

PURPOSE: Robotic-assisted surgery is an alternative technique for patients undergoing minimal invasive cholecystectomy (CHE). The aim of this study is to compare the outcomes and costs of laparoscopic versus robotic CHE, previously described as the major disadvantage of the robotic system, in a single Austrian tertiary center. METHODS: A retrospective single-center analysis was carried out of all patients who underwent an elective minimally invasive cholecystectomy between January 2010 and August 2020 at our tertiary referral institution. Patients were divided into two groups: robotic-assisted CHE (RC) and laparoscopic CHE (LC) and compared according to demographic data, short-term postoperative outcomes and costs. RESULTS: In the study period, 2088 elective minimal invasive cholecystectomies were performed. Of these, 220 patients met the inclusion criteria and were analyzed. One hundred ten (50%) patients underwent LC, and 110 patients RC. There was no significant difference in the mean operation time between both groups (RC: 60.2 min vs LC: 62.0 min; p = 0.58). Postoperative length of stay was the same in both groups (RC: 2.65 days vs LC: 2.65 days, p = 1). Overall hospital costs were slightly higher in the robotic group with a total of €2088 for RC versus €1726 for LC. CONCLUSIONS: Robotic-assisted cholecystectomy is a safe and feasible alternative to laparoscopic cholecystectomy. Since there are no significant clinical and cost differences between the two procedures, RC is a justified operation for training the whole operation team in handling the system as a first step procedure. Prospective randomized trials are necessary to confirm these conclusions.

Clinical and surgical results related to anterior-only multilevel cervical decompression and instrumented fusion for degenerative disease.

Introduction: Anterior-only multilevel cervical decompression and fusion surgery (AMCS) on 3-5-levels is challenging due to potential complications. Also, outcome predictors after AMCS are poorly understood. Research Question: We hypothesize that in patients with at most mild/moderate cervical kyphosis (CK) of the cervical spine, restoration of cervical lordosis (CL) positively influences clinical outcomes. Methods: Analysis of consecutive patients presenting with symptomatic degenerative cervical disease or non-union undergoing AMCS. We measured CL from C2 to C7, Cobb angle of fused levels (fusion angle, FA), C7-Slope, and sagittal vertical axis C2-7 (cSVA, stratified into ≤4cm∖>4cm). Patients with excellent outcome were grouped in BEST-outcomes and with moderate/poor outcomes in WORST-outcomes. Results: We included 244 patients. Fifty-four percent had 3-, 39% 4-level and 7% had 5-level fusion. At mean follow-up of 26 months, 41% of patients achieved BEST-outcome and 23% WORST-outcome. Complications and reoperation rates did not significantly differ. Non-union significantly influenced outcomes. The number of patients with non-union was significantly higher in patients with a preoperative cSVA>4cm (OR 13.1 (95%CI:1.8-96.8). Our model, based on the multivariable analysis with WORST-outcome as outcome variable showed a high accuracy (NPV=73%, PPV=77%, specificity=79%, sensitivity=71%). Discussion and Conclusion: In 3-5-level AMCS, improvement of FA and cSVA were independent predictors of clinical outcome. Improvement of CL positively influenced clinical outcomes and rates of non-union.

Asymptomatic Healthcare Worker PCR Screening during SARS-CoV-2 Omicron Surge, Germany, 2022.

During 2022, a total of 9,515 asymptomatic healthcare workers of a large hospital in Germany underwent SARS-CoV-2 PCR screening twice weekly. Of 398,784 saliva samples, 3,555 (0.89%) were PCR positive (median cycle threshold value 30). Early identification of infected healthcare workers can help reduce SARS-CoV-2 transmission in the hospital environment.

Different ureteral access sheaths sizes for retrograde intrarenal surgery.

PURPOSE: There is a trend toward miniaturization in endourological stone therapy. Good visibility, intrarenal pressures and temperature control should be ensured by ureteral sheaths. In the context of the present study, 10/12 Charr. sheaths and 12/14 Charr. sheaths for flexible ureterorenoscopy were investigated regarding stone-free rate, complication rate and efficacy for laser lithotripsy. METHODS: From January 2020 to January 2022, 100 patients each with kidney stone up to 1.5 cm in diameter were included in the study. Use of a 12/14 Charr. vs. 10/12 Charr. ureteral sheath for flexible ureterorenoscopy was compared. Perioperative data, stone size, volume and density, laser energy, laser duration, stone-free rates and complications based on Clavien-Dindo classification were retrospectively analyzed. RESULTS: For both groups of ureteral access sheaths, there were no differences in median surgery duration (10/12 Charr: 29 min (7-105 min) vs. 12/14 Charr: 34 min (9-95 min); p = 0.33), overall complication rate (p = 0.61) and hospitalization (p = 0.155). There were no differences in stone-free rates (97.9% vs. 92.7%, p = 0.37). Laser lithotripsy duration usingholmium laser was 1.9 min (0.1-10.8 min) vs. 3.8 min (0.2-20.7 min) (p < 0.01) and applied laser energy was 3.1 J (0.15 J-10.29 J) vs. 6.8 J (1.07 J-26.77 J) (p < 0.01) for 12/14 Charr. sheaths and 10/12 Charr. sheaths, respectively. CONCLUSION: In terms of stone-free rates, there are no differences between the 10/12 and 12/14 Charr. ureteral access sheaths. The laser duration and energy was increased with 10/12 Charr. sheaths without showing increased risk for clinical complications like trauma or inflammation.