Comparable low revision rates of stemmed and stemless total anatomic shoulder arthroplasties after exclusion of metal-backed glenoid components: a collaboration between the Australian and Danish national shoulder arthroplasty registries.

BACKGROUND: The stemmed anatomic total shoulder arthroplasty is the gold standard in the treatment of glenohumeral osteoarthritis. However, the use of stemless total shoulder arthroplasties has increased in recent years. The number of revision procedures are relatively low, and therefore it has been recommended that national joint replacement registries should collaborate when comparing revision rates. Therefore, we aimed to compare the revision rates of stemmed and stemless TSA used for the diagnosis of glenohumeral osteoarthritis using data from both the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) and the Danish Shoulder Arthroplasty Registry (DSR). METHODS: We included all patients who were registered in the AOANJRR and the DSR from January 1, 2012, to December 2021 with an anatomic total shoulder arthroplasty used for osteoarthritis. Revision for any reason was used as the primary outcome. We used the Kaplan-Meier method to illustrate the cumulative revision rates and a multivariate cox regression model to calculate the hazard ratios. All analyses were performed separately for data from AOANJRR and DSR, and the results were then reported using a qualitative approach. RESULTS: A total of 13,066 arthroplasties from AOANJRR and 2882 arthroplasties from DSR were included. The hazard ratio for revision of stemmed TSA with stemless TSA as reference, adjusted for age and gender, was 1.67 (95% confidence interval [CI] 1.34-2.09, P < .001) in AOANJRR and 0.57 (95% CI 0.36-0.89, P = .014) in DSR. When including glenoid type and fixation, surface bearing (only in AOANJRR), and hospital volume in the cox regression model, the hazard ratio for revision of stemmed TSA compared to stemless TSA was 1.22 (95% CI 0.85-1.75, P = .286) in AOANJRR and 1.50 (95% CI 0.91-2.45, P = .109) in DSR. The adjusted hazard ratio for revision of total shoulder arthroplasties with metal-backed glenoid components compared to all-polyethylene glenoid components was 2.54 (95% CI 1.70-3.79, P < .001) in AOANJRR and 4.1 (95% CI 1.92-8.58, P < .001) in DSR. CONCLUSION: Based on data from 2 national shoulder arthroplasty registries, we found no significant difference in risk of revision between stemmed and stemless total shoulder arthroplasties after adjusting for the type of glenoid component. We advocate that metal-backed glenoid components should be used with caution and not on a routine basis.

The effects of a fibre-enriched bakery product on glucose, insulin values and appetite. A pilot randomised cross-over trial.

Brewers spent grain (BSG) is a valuable source of arabinoxylans with potential beneficial effects on glucose values. This pilot randomised crossover double-blind trial compared the effects of panettone, a sweet baked-product, enriched with BSG-fibre (p-rich) to unenriched panettone (p-standard) on glucose and insulin blood values and appetite scores. Ten healthy volunteers consumed each food in a random order. Blood variables and appetite scores were assessed at fasting and at different intervals after each food consumption. Glucose values were significantly higher after p-standard intake at 90-min (89.9 ± 16.1 vs 74.6 ± 19.4 mg/dL) and 120-min (81.1 ± 9.85 vs 72.1 ± 14.0 mg/dL). The areas-under-the-curve (AUCs) were lower for both glucose (p = .043) and insulin values (p = .036) with p-rich. At 240-min, satiety was higher (p = .006), and desire-to-eat lower (p = .008) with p-rich; desire-to-eat AUC was lower with p-rich too (p = .029). The integration of a small amount of BSG-derived fibre into a sweet food led to improved glycaemic control and appetite regulation.

Prolonged Exposure for Posttraumatic Stress Disorder in Patients Exhibiting Psychotic Symptoms: A Scoping Review.

BACKGROUND: Trauma is a significant risk factor for developing psychosis. Nevertheless, psychosis is often considered grounds for not receiving trauma-focused therapy due to concerns of exacerbating psychotic symptoms. Prolonged exposure (PE) is a recognized and effective evidence-based therapy modality for the treatment of severe trauma. OBJECTIVE: To assess the available empirical evidence for PE as a feasible treatment programme for posttraumatic stress disorder (PTSD) in patients with psychotic symptoms. METHOD: A systematic literature search was conducted using the databases Scopus, PsycINFO (OVID) and PubMed MEDLINE in December 2023 with a priori defined eligibility criteria. The literature search identified 1226 articles, of which eight met the eligibility criteria. Five studies exploring the effects of PE treatment on patients diagnosed with PTSD and suffering from comorbid psychotic experiences were included. Three studies containing follow-up data or secondary analysis on PTSD and psychotic symptoms from original studies fulfilling the inclusion and exclusion criteria were included. Each study was assessed for quality to estimate the risk of bias. RESULTS: Acknowledging the scarcity of available evidence, the results of the scoping review indicate that PE may be an effective treatment approach for reducing PTSD symptoms in patients with PTSD and comorbid psychotic symptoms. The reviewed studies found no iatrogenic effects, including no increase in psychotic symptoms. CONCLUSION: PE appears to be a possibly effective PTSD treatment for patients suffering from PTSD and comorbid psychotic symptoms or disorders. However, the evidence is scarce, and larger confirmative trials are required for more conclusive evidence.

High revision rate of metal-backed glenoid component and impact on the overall revision rate of stemless total shoulder arthroplasty: a cohort study from the Danish Shoulder Arthroplasty Registry.

BACKGROUND AND PURPOSE: There is controversy regarding the results of stemmed and stemless total shoulder arthroplasty (TSA) used for osteoarthritis. Therefore, we aimed to compare revision rates of stemmed and stemless TSA and to examine the impact of metal-backed glenoid components. METHODS: We included all patients reported to the Danish Shoulder Arthroplasty Register from January 1, 2012 to December 31, 2022 with an anatomical TSA used for osteoarthritis. Primary outcome was revision (removal or exchange of components) for any reason. RESULTS: 3,338 arthroplasties were included. The hazard ratio for revision of stemless TSA adjusted for age and sex was 1.83 (95% confidence interval [CI] 1.21-2.78) with stemmed TSA as reference. When excluding all arthroplasties with a metal-backed glenoid component, the adjusted hazard ratio for revision of stemless TSA was 1.37 (CI 0.85-2.20). For the Eclipse stemless TSA system, the adjusted hazard ratio for revision of a metal-backed glenoid component was 8.75 (CI 2.40-31.9) with stemless Eclipse with an all-polyethylene glenoid component as reference. CONCLUSION:  We showed that the risk of revision of stemless TSAs was increased and that it was related to their combination with metal-backed glenoid components.

Hemorrhage, Disseminated Intravascular Coagulopathy, and Thrombosis Complications Among Critically Ill Patients with COVID-19: An International COVID-19 Critical Care Consortium Study.

OBJECTIVES: To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19. DESIGN: Prospective, observational study. SETTING: Two hundred twenty-nine ICUs across 32 countries. PATIENTS: Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: HECTOR complications occurred in 1,732 of 11,969 study eligible patients (14%). Acute thrombosis occurred in 1,249 patients (10%), including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial ischemia, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic strokes. Hemorrhagic complications were reported in 579 patients (4.8%), including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, 77 (13%) with pulmonary hemorrhage, and 68 (12%) with hemorrhage associated with extracorporeal membrane oxygenation (ECMO) cannula site. Disseminated intravascular coagulation occurred in 11 patients (0.09%). Univariate analysis showed that diabetes, cardiac and kidney diseases, and ECMO use were risk factors for HECTOR. Among survivors, ICU stay was longer (median days 19 vs 12; p < 0.001) for patients with versus without HECTOR, but the hazard of ICU mortality was similar (hazard ratio [HR] 1.01; 95% CI 0.92-1.12; p = 0.784) overall, although this hazard was identified when non-ECMO patients were considered (HR 1.13; 95% CI 1.02-1.25; p = 0.015). Hemorrhagic complications were associated with an increased hazard of ICU mortality compared to patients without HECTOR complications (HR 1.26; 95% CI 1.09-1.45; p = 0.002), whereas thrombosis complications were associated with reduced hazard (HR 0.88; 95% CI 0.79-0.99, p = 0.03). CONCLUSIONS: HECTOR events are frequent complications of severe COVID-19 in ICU patients. Patients receiving ECMO are at particular risk of hemorrhagic complications. Hemorrhagic, but not thrombotic complications, are associated with increased ICU mortality.

Previous rotator cuff repair increases the risk of revision surgery for periprosthetic joint infection after reverse shoulder arthroplasty.

BACKGROUND: Previous studies have indicated an increased risk of periprosthetic joint infection (PJI) in patients treated with reverse shoulder arthroplasty (RSA) compared with patients treated with anatomic total shoulder arthroplasty. The reason for this is unclear but may be related to a high prevalence of previous rotator cuff repair in patients who are treated with RSA. The purpose of this study was to determine previous non-arthroplasty surgery as a risk factor for revision owing to PJI after RSA for cuff tear arthropathy, massive irreparable rotator cuff tears, or osteoarthritis. METHODS: Data were retrieved from the Danish Shoulder Arthroplasty Registry and medical records. We included 2217 patients who underwent RSA for cuff tear arthropathy, massive irreparable rotator cuff tears, or osteoarthritis between 2006 and 2019. PJI was defined as ≥3 of 5 tissue samples positive for the same bacteria or as definite or probable PJI evaluated based on criteria from the International Consensus Meeting. The Kaplan-Meier method was used to illustrate the unadjusted 14-year cumulative rates of revision. A Cox regression model was used to report hazard for revision owing to PJI. Results were adjusted for previous non-arthroplasty surgery, sex, diagnosis, and age. RESULTS: Revision was performed in 88 shoulders (4.0%), of which 40 (1.8%) underwent revision owing to PJI. There were 272 patients (12.3%) who underwent previous rotator cuff repair, of whom 11 (4.0%) underwent revision owing to PJI. The 14-year cumulative rate of revision owing to PJI was 14.1% for patients with previous rotator cuff repair and 2.7% for patients without previous surgery. The adjusted hazard ratio for revision owing to PJI for patients with previous rotator cuff repair was 2.2 (95% confidence interval, 1.04-4.60) compared with patients without previous surgery. CONCLUSION: There is an increased risk of revision owing to PJI after RSA for patients with previous rotator cuff repair. We recommend that patients with previous rotator cuff repair be regarded as high-risk patients when considering RSA.

Stress urinary incontinence is caused predominantly by urethral support failure.

Whales are mammals that can dive to depths of > 1000 m without the high water pressure pushing open their mouth or anus. The same is true for the female urethra. The meatus externus and internus are seals that cannot be pushed open by high water pressures. Recent evidence suggests that the female meatus internus is pushed open when the bladder pressure exceeds the urethral pressure. For a relaxed detrusor, this opening is not possible for at least three reasons: the law of elastic collision, Pascal's law of hydrostatics and the Hagen-Poiseuille law. The three laws do not support that urethral function failure is the predominant cause of stress urinary incontinence (SUI); however, they do support that urethral support failure is. Influential urogynecologists claim the opposite. TVT surgery, according to the integral theory of SUI (IT), has high failure rates because it does not principally prevent the urethra from hanging on a less mobile bladder neck. In the case of a long urethra, the tape is set too distally, and in hypomobile SUI, the use of a tension-free suburethral tape is unwarranted/ineffective, because the proximal urethra is not elevated above its resting position. A successful operation corrects urethral support failure and not urethral function failure.

Good functional outcomes after open reduction and internal fixation for AO/OTA type 13-C2 and -C3 acute distal humeral fractures in patients aged over 45 years.

BACKGROUND: The purpose of this study was to report the functional outcomes and complications after open reduction and internal fixation (ORIF) for Arbeitsgemeinschaft für Osteosynthesefragen (AO)/Orthopaedic Trauma Association (OTA) type 13-C2 and -C3 acute distal humeral fractures with minimum 2-year follow-up. Our hypothesis was that ORIF would provide functional outcomes that are comparable to those of total elbow arthroplasty and elbow hemiarthroplasty reported in the literature. MATERIALS AND METHODS: During a 6-year period, 23 patients aged > 45 years were treated with double plating for AO/OTA type 13-C2 or -C3 fractures. The mean age was 62 years (range, 46-80 years). The Oxford Elbow Score was used as the primary outcome; the Mayo Elbow Performance Score, pain severity score (on a visual analog scale), range of motion, reoperations, and complications were used as secondary outcomes. RESULTS: The median Oxford Elbow Score was 42 (range, 25-48), where a score of 48 represents a normal elbow; 20 patients achieved good to excellent outcomes, and 3 achieved fair outcomes. The median Mayo Elbow Performance Score was 85 (range, 60-100), where a score of 100 represents a normal elbow; 18 patients achieved good to excellent outcomes, and 5 achieved fair outcomes. The median visual analog scale score was 2 (range, 0-5). The median flexion-extension and supination-pronation arcs were 120° (range, 70°-155°) and 160° (range, 75°-170°), respectively. Eight complications were recorded in 7 patients; 4 of them required reoperation because of fracture pseudarthrosis or elbow stiffness. Ten patients were working at the time of trauma, and nine of them returned to the same occupation. Our results are comparable to the results of previously published studies regarding the outcome of ORIF, elbow hemiarthroplasty, or total elbow arthroplasty for AO/OTA type 13-C fractures. CONCLUSION: ORIF is a reliable treatment option for AO/OTA type 13-C2 and -C3 acute distal humeral fractures in middle-aged and elderly patients, despite the considerable rate of complications. Good to excellent results can be obtained in most patients.

Previous surgery for instability is a risk factor for a worse patient-reported outcome after anatomical shoulder arthroplasty for osteoarthritis: a Danish nationwide cohort study of 3,743 arthroplasties.

BACKGROUND AND PURPOSE: Although most patients have good outcomes after shoulder arthroplasty for osteoarthritis, certain risk factors may lead to disappointing outcomes. We assessed risk factors for a worse outcome after anatomical shoulder arthroplasty for osteoarthritis. Our hypothesis was that previous surgery for instability would be a risk factor for a worse outcome independent of age, sex, and arthroplasty type. PATIENTS AND METHODS: We included arthroplasties reported to the Danish Shoulder Arthroplasty Registry between 2006 and 2018 (n = 3,743). The Western Ontario Osteoarthritis of the Shoulder (WOOS) index at 1 year was used as outcome. The total score was converted to a percentage of a maximum score. The general linear model was used to analyze differences in WOOS. Age, sex, arthroplasty type, and previous surgery were included in the multivariate model. Estimates were given with 95% confidence intervals (CI). RESULTS: The mean WOOS score was 78 for patients with no previous surgery and 55 for patients with surgery for instability. The mean difference was -16 (CI -10 to -22) in the multivariate model. Hemiarthroplasty had a worse outcome compared with total shoulder arthroplasty and young patients had a worse outcome compared with older patients. The mean differences in the multivariate model were -12 (CI -10 to -14) and -11 (CI -8 to -14) respectively. INTERPRETATION: Patients with previous surgery for instability had worse results independent of age, sex, and arthroplasty type and should be informed about their individual risk of a worse outcome.

Fat Grafting With Expanded Adipose-Derived Stromal Cells for Breast Augmentation: A Randomized Controlled Trial.

BACKGROUND: The main challenge with fat grafting is loss of some of the graft to postsurgery resorption. Previous studies suggest that adipose-derived stromal cells (ASCs) can improve the volume retention of fat grafts but there is a lack of randomized trials to support the use of ASCs in clinical practice. OBJECTIVES: This trial aimed to investigate whether ASCs improve fat graft volume retention in patients undergoing breast augmentation with lipofilling. METHODS: This was a double-blind, randomized controlled trial of breast augmentation with ASC-enriched fat grafting. Healthy women aged 30 to 45 years were enrolled. First, the participants underwent liposuction to obtain fat for culture expansion of ASCs. Then, the participants were randomly assigned to undergo a 300- to 350-mL breast augmentation with ASC-enriched fat grafting (10 × 106 ASCs/mL fat graft) to 1 of their breasts and placebo-enriched fat grafting of identical volume to the contralateral breast. The primary outcome was fat graft volume retention after a 1-year follow-up measured with MRI. The trial is registered at www.clinicaltrialsregister.eu (EudraCT-2014-000510-59). RESULTS: Ten participants were included in the trial; all completed the treatment and follow-up. No serious adverse events occurred. Fat graft volume retention after 1 year was 54.0% (95% CI, 30.4%-77.6%) in the breasts treated with ASC-enriched fat grafting (n = 10) and 55.9% (95% CI, 28.9%-82.9%) in the contralateral breasts treated with placebo-enriched fat grafting (n = 10) (P = 0.566). CONCLUSIONS: The findings of this trial do not support that ASC-enriched fat grafting is superior to standard fat grafting for breast augmentation.

"Doctor" Badge Promotes Accurate Role Identification and Reduces Gender-Based Aggressions in Female Resident Physicians.

OBJECTIVE: Role misidentification among hospital staff is common. Female resident physicians are more likely to be misidentified as non-physicians. This study utilized a pre-post examination to determine if the usage of a "doctor" badge by resident physicians at a Veterans Affairs Medical Center influences role identification, gender-based aggressions, and workplace experience. METHODS: Twenty-six psychiatry residents at the Veterans Affairs Boston Healthcare System participated in a voluntary, anonymous electronic pre-survey in December 2020 and post-survey in March 2021 to report their experiences with role identification and gender-based aggressions before and after the implementation of a "doctor" badge. RESULTS: Females were significantly more likely than males to report role misidentification (x2(1)=10.8, p=0.001). Females were significantly more likely to experience gender-based aggressions compared to males (x2(1)=19.5, p<0.001). Compared to pre-intervention, females who wore the badge were significantly less likely to be misidentified (x2(1)=9.6, p=0.002). There was no significance when comparing males who were misidentified pre- to post-intervention (x2(1)=1.1, p=0.294). Compared to pre-intervention, females who wore the badge were significantly less likely to experience gender-based aggressions (x2(1)=17.3, p=<0.001). Compared to pre-intervention, there was no significant change in gender-based aggressions for males who wore the badge (x2(1)=1.05, p=0.306). CONCLUSIONS: Female residents were more likely than male residents to report role misidentification. Usage of the "doctor" badge resulted in improved role identification and a reduction in gender-based aggressions for females, but not males. "Doctor" badges can improve role identification, gender-based aggressions, workplace experience, patient communication, and care.

[Risk factors for development of hematotoxicity in elderly patients treated with Linezolid].

Objective: To analyze the clinical data, especially the occurrence of hematotoxicity, of hospitalized elderly patients who took Linezolid (LZD), and to further explore the related risk factors. Methods: Our study enrolled the elderly inpatients treated with linezolid at the Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2018 to September 2021. The hospital information system data were retrieved to retrospectively analyze the clinical characteristics of patients, particularly the clinical characteristics and related risk factors of patients who experienced hematotoxic reactions to LZD. Results: Of the 233 eligible cases included, 103 patients received empirical use of LZD (44.21%). The total effective rate was 76.39% (178/233). Among the 57 effective cases who received blood drug concentration monitoring, the trough concentration of LZD was high in 36.84 % (21/57) of elderly patients. Moreover, there were 15 patients with thrombocytopenia alone, 3 patients with decreased hemoglobin (HB) alone, and 3 patients with both thrombocytopenia and HB decrease. The patients who experienced hematotoxicity (developed a certain degree of hemoglobin decrease and/or thrombocytopenia) were more likely to be complicated with renal impairment (χ²=6.642, P=0.036), concomitantly using proton pump inhibitor (PPI) (χ²=4.566, P=0.033), and had a longer course of LZD treatment (P=0.041). There was no linear correlation between the trough concentration of LZD and glomerular filtration rate evaluated by Modification of Diet in Renal Disease Formula (eGFRMDRD) (R=0.226, P=0.136). Conclusions: The elderly patients, especially those with renal impairment, concomitant treatment with PPI, and a longer course of LZD treatment, exhibited a higher risk of hematotoxicity during LZD treatment. Hence, we should strengthen the protection of renal function, reduce drug interaction, and dynamically monitor the blood drug concentration of LZD to adjust its dose, thus implementing safer and more effective treatments.

What predicts the unsuccess of bariatric surgery? An observational retrospective study.

PURPOSE: Bariatric surgery (BS) has been recognized as an effective treatment for most patients with morbid obesity, but a variable range of patients failed to achieve a successful weight-loss. Controversial data are available about predictors of unsuccess. We aimed to retrospectively assess whether clinical baseline characteristics of patients submitted to sleeve gastrectomy (SL) or gastric bypass (GBP) were associated with unsuccessful weight-loss after 12 and 24-month follow-up. METHODS: Three hundred patients who underwent BS from the 1st January 2016, with at least 24-months follow-up, were enrolled. Patients were divided according to their percentage of excess weight-loss (%EWL) either < 50% or ≥ 50% after 12 and 24-month follow-up. RESULTS: None of the patients was lost at follow-up; 56 (18.7%) patients showed a %EWL < 50% at 24 months. Age, neck circumference, obstructive sleep apnea (OSA) were significantly higher, while total cholesterol and %EWL 6-months lower in those with %EWL < 50% at 12-months. Age, neck circumference, male and OSA rates were increased, while %EWL at 6-months lower in patients with %EWL < 50% at 24-months. In a multiple regression model, age (OR = 1.076; 95% CI 1.029-1.125; p = 0.001; OR = 1.066; 1.027-1.107; p < 0.001) and %EWL at 6-months (OR = 0.876; 0.840-0.913; p < 0.001; OR = 0.950; 0.928-0.972; p < 0.001) were associated with %EWL < 50% both at 12- and 24-months, respectively, and neck circumference (OR = 1.142; 1.011-1.289; p = 0.032) with %EWL < 50% at 24-months. CONCLUSION: Older age, larger neck circumference, and %EWL at 6-months were significantly associated with BS unsuccess, showing almost 90% of those patients an unsuccessful weight-loss early after surgery. Further larger studies with longer follow-up are needed to confirm these results.

Pre-operative micronutrient deficiencies in patients with severe obesity candidates for bariatric surgery.

PURPOSE: In patients with obesity, micronutrient deficiencies have been reported both before and after bariatric surgery (BS). Obesity is a chronic pro-inflammatory status, and inflammation increases the risk of micronutrient malnutrition. Our objective was to assess in pre-BS patients the prevalence of micronutrient deficiencies and their correlation with blood values of C-reactive protein (CRP). METHODS: Anthropometric data, instrumental examinations, and blood variables were centrally measured in the first 200 patients undergoing a pre-BS evaluation at the "Città della Salute e della Scienza" Hospital of Torino, starting from January 2018. RESULTS: At least one micronutrient deficiency was present in 85.5% of pre-BS patients. Vitamin D deficiency was the most prevalent (74.5%), followed by folate (33.5%), iron (32%), calcium (13%), vitamin B12 (10%), and albumin (5.5%) deficiency. CRP values were high (> 5 mg/L) in 65% of the patients. These individuals showed increased rate of iron, folate, vitamin B12 deficiency, and a higher number of micronutrient deficiencies. In a multiple logistic regression model, increased CRP levels were significantly associated with deficiencies of vitamin B12 (OR = 5.84; 95% CI 1.25-27.2; p = 0.024), folate (OR = 4.02; 1.87-8.66; p < 0.001), and with the presence of ≥ 2 micronutrient deficiencies (OR = 2.31; 1.21-4.42; p = 0.01). CONCLUSIONS: Micronutrient deficiencies are common in patients with severe obesity undergoing BS, especially when inflammation is present. In the presence of increased CRP values before surgery, it might be advisable to search for possible multiple micronutrient deficiencies.

Functional Impact of Human Genetic Variants of COL18A1/Endostatin on Pulmonary Endothelium.

Pulmonary arterial hypertension (PAH) is an incurable disease characterized by disordered and dysfunctional angiogenesis leading to small-vessel loss and an obliterative vasculopathy. The pathogenesis of PAH is not fully understood, but multiple studies have demonstrated links between elevated angiostatic factors, disease severity, and adverse clinical outcomes. ES (endostatin), one such circulating angiostatic peptide, is the cleavage product of the proteoglycan COL18A1 (collagen α1[XVIII] chain). Elevated serum ES is associated with increased mortality and disease severity in PAH. A nonsynonymous variant of ES (aspartic acid-to-asparagine substitution at amino acid 104; p.D104N) is associated with differences in PAH survival. Although COL18A1/ES expression is markedly increased in remodeled pulmonary vessels in PAH, the impact of ES on pulmonary endothelial cell (PEC) biology and molecular contributions to PAH severity remain undetermined. In the present study, we characterized the effects of exogenous ES on human PEC biology and signaling. We demonstrated that ES inhibits PEC migration, proliferation, and cell survival, with significant differences between human variants, indicating that they are functional genetic variants. ES promotes proteasome-mediated degradation of the transcriptional repressor ID1, increasing expression and release of TSP-1 (thrombospondin 1). ES inhibits PEC migration via an ID1/TSP-1/CD36-dependent pathway, in contrast to proliferation and apoptosis, which require both CD36 and CD47. Collectively, the data implicate ES as a novel negative regulator of ID1 and an upstream propagator of an angiostatic signal cascade converging on CD36 and CD47, providing insight into the cellular and molecular effects of a functional genetic variant linked to altered outcomes in PAH.

Ceramides and diabetes mellitus: an update on the potential molecular relationships.

Recent evidence suggests that ceramides can play an important pathophysiological role in the development of diabetes. Ceramides are primarily recognized as lipid bilayer building blocks, but recent work has shown that these endogenous molecules are important intracellular signalling mediators and may exert some diabetogenic effects via molecular pathways involved in insulin resistance, ß-cell apoptosis and inflammation. In the present review, we consider the available evidence on the possible roles of ceramides in diabetes mellitus and introduce eight different molecular mechanisms mediating the diabetogenic action of ceramides, categorized into those predominantly related to insulin resistance vs those mainly implicated in ß-cell dysfunction. Specifically, the mechanistic evidence involves ß-cell apoptosis, pancreatic inflammation, mitochondrial stress, endoplasmic reticulum stress, adipokine release, insulin receptor substrate 1 phosphorylation, oxidative stress and insulin synthesis. Collectively, the evidence suggests that therapeutic agents aimed at reducing ceramide synthesis and lowering circulating levels may be beneficial in the prevention and/or treatment of diabetes and its related complications.

Urethral closure occurs by recoiling, pressure transmission, and a guarding reflex.

Enhörning's abdominal pressure transmission theory (ET) is built on Pascal's law of fluid pressures. A theory that rejects ET also rejects this basic physical law and cannot be considered scientifically sound. The integral theory (IT) of female stress urinary incontinence rejects ET. This issue is discussed from the viewpoint of the urethral hanging theory of female stress urinary incontinence (UHT).

The urethral hanging theory and how it relates to Enhörning's theory and the integral theory.

INTRODUCTION AND HYPOTHESIS: The article discusses three theories of stress urinary incontinence, the urethral hanging theory, Enhörning's theory, and the integral theory. METHODS: The abdominal pressure transmission theory proposed by Enhörning is often misunderstood. It is regularly interpreted to mean that, in cases of stress urinary incontinence, the bladder neck descends outside the abdominal cavity, and treatment must involve elevating or repositioning the bladder neck. RESULTS: However, this actually contradicts the information provided in Enhörning's original paper. The urethral hanging theory accepts the core of Enhörning's theory and the integral theory rejects it. The three theories have different views on closure and opening of the bladder neck and on the pathophysiology of urethral funneling. CONCLUSION: These differences are described and discussed.

PATCHING RETINAL BREAKS WITH HEALAFLOW IN 27-GAUGE VITRECTOMY FOR THE TREATMENT OF RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To report the surgical outcomes of primary rhegmatogenous retinal detachment (RRD) repaired by 27-gauge pars plana vitrectomy combined with Healaflow patch and air tamponade. METHODS: In an initial vitro experiment, we observed and compared the dissolution and displacement of the dispersion spots of 0.05-mL Healaflow and sodium hyaluronate. We then performed a prospective, interventional cohort study on 38 eyes in 37 consecutive patients with primary rhegmatogenous retinal detachment. All eyes underwent pars plana vitrectomy combined with Healaflow patch and air tamponade; the postoperative period did not involve prone positioning. The primary and final anatomical attachment rate, best-corrected visual acuity, and intraoperative and postoperative complications were evaluated. RESULTS: In the in vitro experiment, the viscoelastic Healaflow remained adherent with no change in the size of the area; however, the control dissolved completely in the balance solution. The patient study included 16 women (43.2%) and 21 men (56.8%) (mean age, 59.5 ± 9.5 years; mean follow-up period, 8.9 ± 3.8 months). A single break was present in 21 (55.3%) and 2 to 5 breaks in 17 cases (44.8%). The macula was involved in 25 (65.8%) and attached in 13 cases (34.2%) intraoperatively. Initial reattachment was achieved in 37 (97.4%) and final reattachment in 38 cases (100%). In one case (2.6%), the macula redetached because of failure of the chorioretinal scar to develop around the treated break. Mean preoperative and postoperative best-corrected visual acuities were 1.02 ± 0.82 logarithm of the minimum angle of resolution (median Snellen acuity: 20/125, range: 20/20,000-20/20) and 0.23 ± 0.17 logarithm of the minimum angle of resolution (median Snellen acuity: 20/32, range: 20/100-20/20), respectively (P < 0.001). Intraocular pressure was elevated transiently in 28 eyes (73.7%). There were no other intraoperative complications or postoperative scleral incision leakage. CONCLUSION: A 27-gauge pars plana vitrectomy combined with Healaflow patch, and air tamponade results in a high reattachment rate in the treatment of rhegmatogenous retinal detachment. Thus, patients can benefit from early visual recovery and less complications.

Five-Year Mortality Hazard Is Reduced In Chronic Obstructive Pulmonary Disease Patients Receiving Double- versus Single-Lung Transplants.

BACKGROUND: Previous studies suggest double-lung transplant (DLT) may be associated with superior survival compared to single-lung transplantation (SLT) in chronic obstructive pulmonary disease (COPD) recipients. The purpose of this study was to compare survival in patients with COPD undergoing DLT versus SLT since the inception of the lung allocation score. METHODS: We used the United Network for Organ Sharing database to retrospectively identify adult patients with COPD who underwent isolated lung transplantation from 5/4/2005-12/31/2014. We then separated patients into DLT versus SLT. Short-term (1 y) and long-term survival (5 y) were compared between DLT and SLT cohorts by the method of Kaplan-Meier, and Cox proportional hazards modeling was used to adjust for case mix. RESULTS: Four thousand eight hundred thirty-two COPD patients were listed, and 3554 underwent lung transplantation over the study period, including 1358 SLTs (38%) and 2196 DLTs (62%). Survival 1 y after listing was 93% for those remaining wait listed (n = 1892) versus 91% for SLT (n = 1093) versus 89% for DLT (n = 1847) (log-rank P < 0.01). Survival at 1 y after transplant was 88% for both SLT and DLT groups (log-rank P = 0.93); however, 5-y survival was significantly lower after SLT (51% versus 59%, log-rank P < 0.01). After risk adjustment, hazard for 1-y mortality after DLT was not significantly reduced compared to SLT (hazard ratio 0.89 [0.69-1.14], P = 0.36) but was significantly reduced 5 y after DLT (hazard ratio 0.88 [0.78-0.99], P = 0.04). CONCLUSIONS: In the largest survival analysis of COPD recipients since the inception of the lung allocation score, the hazard for 5-y mortality was significantly reduced in recipients who underwent DLT as compared to SLT.