Methods for non-proportional hazards in clinical trials: A systematic review.

For the analysis of time-to-event data, frequently used methods such as the log-rank test or the Cox proportional hazards model are based on the proportional hazards assumption, which is often debatable. Although a wide range of parametric and non-parametric methods for non-proportional hazards has been proposed, there is no consensus on the best approaches. To close this gap, we conducted a systematic literature search to identify statistical methods and software appropriate under non-proportional hazard. Our literature search identified 907 abstracts, out of which we included 211 articles, mostly methodological ones. Review articles and applications were less frequently identified. The articles discuss effect measures, effect estimation and regression approaches, hypothesis tests, and sample size calculation approaches, which are often tailored to specific non-proportional hazard situations. Using a unified notation, we provide an overview of methods available. Furthermore, we derive some guidance from the identified articles.

Which parameters influence cognitive, psychiatric and long-term seizure outcome in mesial temporal lobe epilepsy after selective amygdalohippocampectomy?

BACKGROUND: We aimed to analyze potentially prognostic factors which could have influence on postoperative seizure, neuropsychological and psychiatric outcome in a cohort of patients with mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS) after selective amygdalohippocampectomy (SAHE) via transsylvian approach. METHODS: Clinical variables of 171 patients with drug-resistant MTLE with HS (88 females) who underwent SAHE between 1994 and 2019 were evaluated using univariable and multivariable logistic regression models, to investigate which of the explanatory parameters can best predict the outcome. RESULTS: At the last available follow-up visit 12.3 ± 6.3 years after surgery 114 patients (67.9%) were seizure-free. Left hemispheric MTLE was associated with worse postoperative seizure outcome at first year after surgery (OR = 0.54, p = 0.01), female sex-with seizure recurrence at years 2 (OR = 0.52, p = 0.01) and 5 (OR = 0.53, p = 0.025) and higher number of preoperative antiseizure medication trials-with seizure recurrence at year 2 (OR = 0.77, p = 0.0064), whereas patients without history of traumatic brain injury had better postoperative seizure outcome at first year (OR = 2.08, p = 0.0091). All predictors lost their predictive value in long-term course. HS types had no prognostic influence on outcome. Patients operated on right side performed better in verbal memory compared to left (VLMT 1-5 p < 0.001, VLMT 7 p = 0.001). Depression occurred less frequently in seizure-free patients compared to non-seizure-free patients (BDI-II Z = - 2.341, p = 0.019). CONCLUSIONS: SAHE gives an improved chance of achieving good postoperative seizure, psychiatric and neuropsychological outcome in patients with in MTLE due to HS. Predictors of short-term outcome don't predict long-term outcome.

Red blood cell transfusion-related dynamics of extracellular vesicles in intensive care patients: a prospective subanalysis.

Extracellular vesicles (EVs) accumulate during packed red blood cell (PRBC) storage. To date, the involvement of EVs in transfusion-related immunomodulation (TRIM) has not been prospectively evaluated in intensive care unit (ICU) patients. This was a prospective subanalysis of a recent observational feasibility study in postoperative ICU patients after: (1) open aortic surgery (Aorta), (2) bilateral lung transplantation (LuTx), and (3) other types of surgery (Comparison). Patient plasma was collected three times each before and after leukoreduced PRBC transfusion at 30-min intervals. The total number of EVs and EVs derived from erythrocytes (EryEVs), total platelets (total PEVs), activated platelets, granulocytes (GEVs), monocytes, and myeloid cells in PRBC samples and patient plasma were analyzed by flow cytometry. Statistical analysis was performed by Spearman's correlation test, linear mixed models and pairwise comparisons by Wilcoxon matched-pairs test. Twenty-three patients (Aorta n = 5, LuTx n = 9, Comparison n = 9) were included in the final analysis. All EV subgroups analyzed were detectable in all PRBCs samples (n = 23), but concentrations did not correlate with storage time. Moreover, all EVs analyzed were detectable in all plasma samples (n = 138), and EV counts were consistent before transfusion. Concentrations of total EVs, EryEVs, total PEVs, and GEVs increased after transfusion compared with baseline in the entire cohort but not in specific study groups. Furthermore, the change in plasma EV counts (total EVs and EryEVs) after transfusion correlated with PRBC storage time in the entire cohort. Extracellular vesicles were detectable in all PRBC and plasma samples. Individual EV subtypes increased after transfusion in the entire cohort, and in part correlated with storage duration. Future clinical studies to investigate the role of EVs in TRIM are warranted and should anticipate a larger sample size.Trial registration: Clinicaltrials.gov: NCT03782623.

Influence of drusenoid pigment epithelial detachments on the progression of age-related macular degeneration and visual acuity.

OBJECTIVE: To analyze the presence and morphologic characteristics of drusenoid pigment epithelial detachments (DPEDs) in spectral-domain optical coherence tomography (SD-OCT) in Caucasian patients with early and intermediate age-related macular degeneration (AMD) as well as the influence of these characteristics on best-corrected visual acuity (BCVA) and disease progression. DESIGN: Prospective observational cohort study. PARTICIPANTS: 89 eyes of 56 patients with early and intermediate AMD. METHODS: Examinations consisted of BCVA, SD-OCT, and indocyanine green angiography. Evaluated parameters included drusen type, mean drusen height and -volume, the presence of DPED, DPED maximum height, -maximum diameter, -volume, topographic location, the rate of DPED collapse, and the development of macular neovascularization (MNV) or geographic atrophy (GA). RESULTS: DPED maximum height (162.34 µm ± 75.70 µm, p = 0.019) was significantly associated with the development of GA and MNV. For each additional 100 µm in maximum height, the odds of developing any late AMD (GA or MNV) increased by 2.23 (95% CI = 1.14-4.35). The presence of DPED (44 eyes, p = 0.01), its volume (0.20 mm ± 0.20 mm, p = 0.01), maximum diameter (1860.87 µm ± 880.74 µm, p = 0.03), maximum height (p < 0.001) and topographical location in the central millimetre (p = 0.004) of the Early Treatment Diabetic Retinopathy Study (ETDRS)-Grid were significantly correlated with BCVA at the last follow-up (0.15logMAR ± 0.20logMAR; Snellen equivalent approximately 20/28). DPEDs occurred significantly less in the outer quadrants than in the central millimetre and inner quadrants of ETDRS-Grid (all p values < 0.001). CONCLUSIONS: The height of drusen and DPEDs is a biomarker that is significantly associated with the development of late AMD and visual loss. DPEDs affect predominantly the center and inner quadrants of the ETDRS-Grid.

Analysing early changes of photoreceptor layer thickness following surgery in eyes with epiretinal membranes.

BACKGROUND/OBJECTIVES: To analyse short-term changes of mean photoreceptor thickness (PRT) on the ETDRS-grid after vitrectomy and membrane peeling in patients with epiretinal membrane (ERM). SUBJECTS/METHODS: Forty-eight patients with idiopathic ERM were included in this prospective study. Study examinations comprised best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) before surgery, 1 week (W1), 1 month (M1) and 3 months (M3) after surgery. Mean PRT was assessed using an automated algorithm and correlated with BCVA and central retinal thickness (CRT). RESULTS: Regarding PRT changes of the study eye in comparison to baseline values, a significant decrease at W1 in the 1 mm, 3 mm and 6 mm area (all p-values < 0.001), at M1 (p = 0.009) and M3 (p = 0.019) in the central 1 mm area, a significant increase at M3 in the 6 mm area (p < 0.001), but no significant change at M1 in the 3 mm and 6 mm area and M3 in the 3 mm area (all p-values > 0.05) were observed. BCVA increased significantly from baseline to M3 (0.3LogMAR-0.15LogMAR, Snellen equivalent = 20/40-20/28 respectively; p < 0.001). There was no correlation between baseline PRT and BCVA at any visit after surgery, nor between PRT and BCVA at any visit (all p-values > 0.05). Decrease in PRT in the 1 mm (p < 0.001), 3 mm (p = 0.013) and 6 mm (p = 0.034) area after one week correlated with the increase in CRT (449.9 µm-462.2 µm). CONCLUSIONS: Although the photoreceptor layer is morphologically affected by ERMs and after their surgical removal, it is not correlated to BCVA. Thus, patients with photoreceptor layer alterations due to ERM may still benefit from surgery and achieve good functional rehabilitation thereafter.

Ventilatory support and inflammatory peptides in hospitalised patients with COVID-19: A prospective cohort trial.

PURPOSE: Several studies have shown that SARS-CoV-2 can induce a massive release of cytokines which contributes to disease severity and mortality. Therefore, cytokine levels in the serum may help to predict disease severity and survival in COVID-19 patients. METHODS: In this prospective trial, 88 patients who were hospitalised for COVID-19 were enrolled. Blood samples for serum peptide measurements were taken at the time closest to hospitalisation, at day 5, 9 and 13 (±1). The concentrations of cytokines (IL-1α, IL-1ß, IL-1RA, IL-6, L-7, L-10, IFN-γ and TNF-α), chemokines (CCL-3, CCL-4 and CCL-7) and growth factors (G-CSF, GM-CSF and VEGF) were assessed and correlated with the type of ventilation, occurrence of consolidations on imaging and the level of care. RESULTS: COVID-19 patients (median age 68 years, IQR 55-77) stayed in hospital between 5-171 days. Compared to patients in the general care unit, patients in the intermediate care unit (IMCU) and intensive care unit (ICU) presented significantly elevated serum IL-6 (p = 0.004) and lower IFN-γ levels (p = 0.005), respectively. The peak inspiratory pressure in ventilated patients correlated positively with IL-1RA, G-CSF and inversely with IFN-γ serum levels (all p<0.05). VEGF serum levels inversely correlated with the fraction of inspired oxygen in patients receiving high-flow nasal canula oxygen therapy (p = 0.047). No significant correlation between serum concentrations of the measured peptides and the type of ventilation, occurrence of radiological consolidations or in-hospital mortality has been observed. CONCLUSION: IL1-RA, IL-6, IFN-γ, G-CSF, CCL-7 and VEGF serum levels could prove helpful as biomarkers to assess disease severity and the need for intensive care in COVID-19 patients.

The "real life" efficacy of dupilumab is independent of initial polyp size and concomitant steroids in CRSwNP.

BACKGROUND: Dupilumab significantly improves symptom control in chronic rhinosinusitis with nasal polyps (CRSwNP). Patients with large polyps at the initiation of treatment (total polyp score (TPS) ≥ 5) have been the focus in published studies. Patients with significant burden of disease but small polyps (TPS ≤ 4) have not yet been evaluated for clinical response. This study set out to evaluate the benefit of dupilumab treatment on cohorts of small (TPS ≤ 4) compared to large polyps (TPS ≥ 5). Furthermore, benefit of concomitant oral and/or nasal steroid therapy has been evaluated. METHODS: 97 patients with CRSwNP, who were begun on dupilumab between January 2020 and October 2021, were included. All patients were followed-up for 6 months. At each visit they underwent nasal endoscopy, smell identification tests and filled out validated patient questionnaires. RESULTS: Significant drops in TPS were seen in both patient groups after 6 months of therapy, dropping from a median score of 3 to 0 and from 6 to 2 in patients with small and large polyps respectively. Furthermore, a linear mixed model calculated a drop of 22% and 24% in TPS per month in patients with small and large polyps respectively with no significant difference in rate of decline. Finally the model showed that neither oral nor nasal steroids influenced the rate of response to dupilumab therapy. CONCLUSIONS: Polyp size at the initiation of dupilumab therapy and whether patients continue to take steroid therapy does not appear to influence effectiveness of dupilumab treatment.

Development of a localization-based algorithm for the prediction of leg ulcer etiology.

BACKGROUND: Diagnostic work-up of leg ulcers is time- and cost-intensive. This study aimed at evaluating ulcer location as a diagnostic criterium and providing a diagnostic algorithm to facilitate differential diagnosis. PATIENTS AND METHODS: The study consisted of 277 patients with lower leg ulcers. The following five groups were defined: Venous leg ulcer, arterial ulcers, mixed ulcer, arteriolosclerosis, and vasculitis. Using computational surface rendering, predilection sites of different ulcer types were evaluated. The results were integrated in a multinomial logistic regression model to calculate the likelihood of a specific diagnosis depending on location, age, bilateral involvement, and ulcer count. Additionally, neural network image analysis was performed. RESULTS: The majority of venous ulcers extended to the medial malleolar region. Arterial ulcers were most frequently located on the dorsal aspect of the forefoot. Arteriolosclerotic ulcers were distinctly localized at the middle third of the lower leg. Vasculitic ulcers appeared to be randomly distributed and were markedly smaller, multilocular and bilateral. The multinomial logistic regression model showed an overall satisfactory performance with an estimated accuracy of 0.68 on unseen data. CONCLUSIONS: The presented algorithm based on ulcer location may serve as a basic tool to narrow down potential diagnoses and guide further diagnostic work-up.

The Effect of Oral Nimodipine on Cerebral Metabolism and Hemodynamic Parameters in Patients Suffering Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: Nimodipine is routinely administered to aneurysmal subarachnoid hemorrhage patients to improve functional outcomes. Nimodipine can induce marked systemic hypotension, which might impair cerebral perfusion and brain metabolism. METHODS: Twenty-seven aneurysmal subarachnoid hemorrhage patients having multimodality neuromonitoring and oral nimodipine treatment as standard of care were included in this retrospective study. Alterations in mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), brain tissue oxygen tension (pbtO2), and brain metabolism (cerebral microdialysis), were investigated up to 120 minutes after oral administration of nimodipine (60 mg or 30 mg), using mixed linear models. RESULTS: Three thousand four hundred twenty-five oral nimodipine administrations were investigated (126±59 administrations/patient). After 60 mg of oral nimodipine, there was an immediate statistically significant (but clinically irrelevant) drop in MAP (relative change, 0.97; P<0.001) and CPP (relative change: 0.97; P<0.001) compared with baseline, which lasted for the whole 120 minutes observation period (P<0.001). Subsequently, pbtO2 significantly decreased 50 minutes after administration (P=0.04) for the rest of the observation period; the maximum decrease was -0.6 mmHg after 100 minutes (P<0.001). None of the investigated cerebral metabolites (glucose, lactate, pyruvate, lactate/pyruvate ratio, glutamate, glycerol) changed after 60 mg nimodipine. Compared with 60 mg nimodipine, 30 mg induced a lower reduction in MAP (relative change, 1.01; P=0.02) and CPP (relative change, 1.01; P=0.03) but had similar effects on pbtO2 and cerebral metabolism (P>0.05). CONCLUSIONS: Oral nimodipine reduced MAP, which translated into a reduction in cerebral perfusion and oxygenation. However, these changes are unlikely to be clinically relevant, as the absolute changes were minimal and did not impact cerebral metabolism.

Preoperative BChE serves as a prognostic marker in patients with resectable AEG after neoadjuvant chemotherapy.

BACKGROUND: Diminished systemic serum butyrylcholinesterase (BChE), a biomarker for chronic inflammation, cachexia, and advanced tumor stage, has shown to play a prognostic role in various malignancies. The aim of this study was to investigate the prognostic value of pretherapeutic BChE levels in patients with resectable adenocarcinoma of the gastroesophageal junction (AEG), treated with or without neoadjuvant therapy. METHODS: Data of a consecutive series of patients with resectable AEG at the Department for General Surgery, Medical University of Vienna, were analyzed. Preoperative serum BChE levels were correlated to clinic-pathological parameters as well as treatment response. The prognostic impact of serum BChE levels on disease-free (DFS) and overall survival (OS) was evaluated by univariate and multivariate cox regression analysis, and Kaplan-Meier curves used for illustration. RESULTS: A total of 319 patients were included in this study, with an overall mean (standard deviation, SD) pretreatment serum BChE level of 6.22 (± 1.91) IU/L. In univariate models, diminished preoperative serum BChE levels were significantly associated with shorter overall (OS, p < 0.003) and disease-free survival (DFS, p < 0.001) in patients who received neoadjuvant treatment and/or primary resection. In multivariated analysis, decreased BChE was significantly associated with shorter DFS (HR: 0.92, 95% CI: 0.84-1.00, p 0.049) and OS (HR: 0.92, 95% CI: 0.85-1.00, p < 0.49) in patients receiving neoadjuvant therapy. Backward regression identified the interaction between preoperative BChE and neoadjuvant chemotherapy as a predictive factor for DFS and OS. CONCLUSION: Diminished serum BChE serves as a strong, independent, and cost-effective prognostic biomarker for worse outcome in patients with resectable AEG who had received neoadjuvant chemotherapy.

MELD-Na Alterations on the Liver Transplant Waiting List and Their Impact on Listing Outcome.

BACKGROUND: Dynamic MELD deterioration (Delta MELD) during waiting time was shown to have significant impact on post-transplant survival. The aim of this study was to analyze the impact of MELD-Na score alterations on waiting list outcomes in liver transplant candidates. METHOD: 36,806 patients listed at UNOS for liver transplantation in 2011-2015 were analyzed according to their delisting reasons. Several different MELD-Na alterations during waiting time were analyzed (e.g., maximal change, last change before delisting/transplantation). Outcome estimates were calculated according to MELD-Na scores at listing and Delta MELD. RESULTS: Patients who died while on the waiting list showed a significantly higher deterioration in MELD-Na during the waiting time (6.8 ± 8.4 points) than stable patients who remained actively listed (-0.1 ± 5.2 points; p < 0.01). Patients who were considered too healthy for transplantation improved by more than 3 points on average during the waiting time. The mean peak MELD-Na alteration during the waiting time was 10.0 ± 7.6 for patients who died on the waiting list, compared to 6.6 ± 6.1 in the group of patients who finally underwent transplantation. CONCLUSIONS: Deterioration of MELD-Na during waiting time and maximal MELD-Na deterioration have a significant negative impact on the liver transplant waiting list outcome.

FACE-Q Patient Report-Assisted Subjective and Objective Evaluation of Blepharoplasty Outcomes Using Two Different Suturing Techniques: A Randomized and Patient-Blinded Pilot Study.

BACKGROUND: /Objectives To compare two suturing techniques in patients undergoing upper eyelid blepharoplasty by using the FACE-Q™ Eye Module questionnaire to assess patient-reported outcomes and by blinded Likert-scale gradings of two experienced surgeons. METHODS: 90 patients undergoing bilateral blepharoplasty were randomly assigned to a suturing technique (running cutaneous or subcuticular closure) using Prolene 6.0. Patients completed the FACE-Q eye module questionnaire before surgery and 7 days and 3 months after surgery. Further, two trained oculoplastic surgeons assessed the outcome. FACE-Q ratings were RASCH-transformed, and linear models were fitted for appraisal and satisfaction results. Intraclass correlation coefficient (ICC) was calculated to assess the surgeons' rating agreement. RESULTS: There was no statistically significantly difference in patients' FACE-Q self-assessments regarding satisfaction with eyes and appraisal of upper eyelids between the two suturing techniques investigated, both 7 days and 3 months after blepharoplasty. The more content the patient at baseline, the less the increase in satisfaction after 3 months. There was good agreement between blinded graders in outcome assessment expressed by an ICC of 0.86. Dry-eye symptoms increased after surgery, independent of the suturing technique, patient age or sex. CONCLUSION: In conclusion, this study shows that post operative patient satisfaction is independent of suturing technique, but depends on baseline FACE-Q reports. These findings are valuable in patient communication and selection and are in line with observer-based assessments. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Red blood cell transfusion-related eicosanoid profiles in intensive care patients-A prospective, observational feasibility study.

Introduction: Eicosanoids are bioactive lipids present in packed red blood cells (PRBCs), and might play a role in transfusion-related immunomodulation (TRIM). We tested the feasibility of analyzing eicosanoid profiles in PRBC supernatant and in plasma samples of postoperative intensive care unit (ICU) patients transfused with one unit of PRBCs. Methods: We conducted a prospective, observational feasibility study enrolling postoperative ICU patients: 1) patients treated with acetylsalicylic acid following abdominal aortic surgery (Aorta); 2) patients on immunosuppressants after bilateral lung transplantation (LuTx); and 3) patients undergoing other types of major surgery (Comparison). Abundances of arachidonic acid (AA) and seven pre-defined eicosanoids were assessed by liquid chromatography and tandem mass spectrometry. PRBC supernatant was sampled directly from the unit immediately prior to transfusion. Spearman's correlations between eicosanoid abundance in PRBCs and storage duration were assessed. Patient plasma was collected at 30-min intervals: Three times each before and after transfusion. To investigate temporal changes in eicosanoid abundances, we fitted linear mixed models. Results: Of 128 patients screened, 21 were included in the final analysis (Aorta n = 4, LuTx n = 8, Comparison n = 9). In total, 21 PRBC and 125 plasma samples were analyzed. Except for 20-hydroxyeicosatetraenoic acid (HETE), all analyzed eicosanoids were detectable in PRBCs, and their abundance positively correlated with storage duration of PRBCs. While 5-HETE, 12-HETE/8-HETE, 15-HETE, 20-HETE, and AA were detectable in virtually all plasma samples, 9-HETE and 11-HETE were detectable in only 57% and 23% of plasma samples, respectively. Conclusions: Recruitment of ICU patients into this transfusion study was challenging but feasible. Eicosanoid abundances increased in PRBC supernatants during storage. In plasma of ICU patients, eicosanoid abundances were ubiquitously detectable and showed limited fluctuations over time prior to transfusion. Taken together, larger clinical studies seem warranted and feasible to further investigate the role of PRBC-derived eicosanoids in TRIM.

OCTA Biomarker Search in Patients with nAMD: Influence of Retinal Fluid on Time-Dependent Biomarker Response.

PURPOSE: Previous studies have identified a link between optical coherence tomography (OCT)-derived and OCT angiography (OCTA)-based parameters in patients with neovascular AMD (nAMD); the latter may serve as direct biomarkers for macular neovascularization (MNV) activity. The aim of this study was to assess the individual influence of retinal thickness (RT) as well as intra- and sub-retinal fluid (IRF, SRF) presence on the treatment response over time as assessed by previously identified OCTA-derived MNV vascular parameters. METHODS: During the first 3 months of anti-VEGF therapy patients were prospectively followed. RT, SRF and IRF were determined from SSOCT/A (PlexElite, Zeiss) images and using the semi-automated AngioTool software, vessel area (VA), total vessel length (TVL), total number of junctions (TNJ), junction density (JD), vessel density (VD) as well as MNV area were exported. IRF and SRF were identified manually on OCT volume scans .The associations between RT, IRF, and SRF and SSOCTA vascular parameters were analyzed using linear mixed models. RESULTS: 31 eyes of 31 patients with treatment-naïve and OCTA-positive nAMD MNV were included in this analysis. VA, TVL, TNJ, and MNV area show a statistically significant change over time in response to anti-VEGF treatment, even after correcting for the presence of SRF, IRF, or RT (all p < 0.05). This is not the case for JD and VD (both p > 0.05). CONCLUSIONS: OCTA-based parameters VA, TVL, TNJ, and MNVarea show a strong response to anti-VEGF therapy over time, independent of the presence of IRF, SRF or RT. We conclude that the above listed OCTA parameters could contribute to our understanding of MNV biology and to guide individualized treatment in the future. TRIAL REGISTRY: The authors confirm that all ongoing and related trials are registered. ClinicalTrials.gov Number: NCT02521142.

The male patient with obesity undergoing metabolic and bariatric surgery: changes in testosterone levels correlate with weight loss after one-anastomosis gastric bypass and Roux-en-Y gastric bypass.

BACKGROUND: Male obesity secondary hypogonadism (MOSH) is a common disease among men with obesity and can be associated with metabolic syndrome and a variety of metabolic problems ultimately leading to androgen deficiency. Metabolic and bariatric surgery is a well-established treatment option associated with significant weight loss and reduction in metabolic co-morbidities. OBJECTIVES: To evaluate the impact of surgery on plasma levels of sexual hormones and their effect on weight loss comparing 2 surgical methods (one-anastomosis gastric bypass [OAGB] and Roux-en-Y gastric bypass [RYGB]) in male patients with obesity. SETTING: University hospital, Austria. METHODS: Patients undergoing OAGB and RYGB between 2012 and 2017 were analyzed retrospectively. Follow-up in this study was up to 24 months. Systemic levels of sexual hormones (luteinizing hormone [LH]), follicle stimulating hormone [FSH], total testosterone [TT], sexual hormone binding globin [SHBG], 17 beta-estradiol [17bE], androstenedione [AS]) were retrieved at each visit. A linear mixed model was used to assess the correlation between changes in testosterone levels and percent excess weight loss (%EWL). RESULTS: In 30.8% of all patients, MOSH was present preoperatively. A significant increase of TT was observed postoperatively that led to a complete resolution of hypogonadism within the period observed. Bioavailable testosterone (bTT) and FSH levels significantly increased each month of follow-up after surgery (all P < .01). Levels of 17bE did not change significantly after surgery. The overall change of TT, comparing preoperative and 1-year postoperative TT levels (ΔTT), significantly correlated with %EWL. Changes in TT levels were not affected by the choice of surgical method. CONCLUSIONS: Serum plasma testosterone levels rise significantly after metabolic and bariatric surgery in male patients. The change of testosterone levels seems to play a role in continued weight loss after surgery. This is true irrespective of the surgical method used.

Stroke Volume and Arterial Pressure Fluid Responsiveness in Patients With Elevated Stroke Volume Variation Undergoing Major Vascular Surgery: A Prospective Intervention Study.

OBJECTIVES: The identification of potential hemodynamic indicators to increase the predictive power of stroke-volume variation (SVV) for mean arterial pressure (MAP) and stroke volume (SV) fluid responsiveness. DESIGN: A prospective intervention study. SETTING: At a single-center university hospital. PARTICIPANTS: Nineteen patients during major vascular surgery with 125 fluid interventions. INTERVENTIONS: When SVV ≥13% occurred for >30 seconds, 250 mL of Ringer's lactate were given within 2 minutes. MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables, such as pulse-pressure variation (PPV) and dynamic arterial elastance (Edyn), were measured by pulse power-wave analysis. The outcomes were MAP and SV responsiveness, defined as an increase of at least 10% of MAP and SV within 5 minutes of the fluid intervention. Of the fluid interventions, 48% were MAP-responsive, and 66% were SV-responsive. The addition of PPV and Edyn cut-off values to the SVV cut-off decreased sensitivity from 1-to-0.66 to-0.82, and concomitantly increased specificity from 0-to- 0.65-to-0.93 for the prediction of MAP and SV responsiveness in the authors' study setting. The areas under the receiver operating characteristic curves of PPV and Edyn for the prediction of MAP responsiveness were 0.79 and 0.75, respectively. The areas under the receiver operating characteristic curves for PPV and Edyn to predict SV responsiveness were 0.85 and 0.77, respectively. CONCLUSIONS: The PPV and Edyn showed good accuracy for the prediction of MAP and SV responsiveness in patients with elevated SVV during vascular surgery. Either PPV or Edyn may be used in conjunction with SVV to better predict MAP and SV fluid responsiveness in patients undergoing vascular surgery.

Distal locking technique affects the rate of iatrogenic radial nerve palsy in intramedullary nailing of humeral shaft fractures.

BACKGROUND: Intramedullary humeral nailing is a common and reliable procedure for the treatment of humeral shaft fractures. Radial nerve palsy is a common complication encountered in the treatment of this pathology. The radial nerve runs from posterior to anterior at the lateral aspect of the distal humerus. Hence, there is reason to believe that due to the anatomic vicinity of the radial nerve in this area, lateral-medial distal locking in intramedullary nailing of the humerus may be associated with a greater risk for iatrogenic radial nerve injury compared to anterior-posterior locking. QUESTIONS/PURPOSE: To assess whether the choice of distal locking (lateral-medial versus anterior-posterior distal locking) in intramedullary humeral nailing of humeral shaft fractures affects the risk for iatrogenic radial nerve injury. PATIENTS AND METHODS: Overall, 203 patients (116 females, mean age 64.3 ± 18.6 years), who underwent intramedullary nailing of the humerus between 2000 and 2020 at a single level-one trauma center, met the inclusion criteria and were analyzed in this retrospective case-control study. Patients were subdivided into two groups according to the distal locking technique. RESULTS: Anterior-posterior locking was performed in 176 patients versus lateral-medial locking in 27 patients. We observed four patients with iatrogenic radial nerve palsy in both groups. Risk for iatrogenic radial nerve palsy was almost 7.5 times higher for lateral-medial locking (OR 7.48, p = 0.006). There was no statistically significant difference regarding intraoperative complications, union rates or revision surgeries between both groups. CONCLUSIONS: Lateral-medial distal locking in intramedullary nailing of the humerus may be associated with a greater risk for iatrogenic radial nerve palsy than anterior-posterior locking. Hence, we advocate for anterior-posterior locking. LEVEL OF EVIDENCE: Level III retrospective comparative study.