Impact of the coronavirus disease 2019 pandemic on aortic valve replacement and outcomes in France.

BACKGROUND: The coronavirus disease of 2019 (COVID-19) pandemic lockdowns limited access to medical care. The impact on surgical (SAVR) and transcatheter (TAVR) aortic valve replacement (AVR) has been poorly described. AIM: We sought to evaluate the impact of the COVID-19 pandemic on the number and modalities of AVR, patient demographics and in-hospital outcomes at the nationwide level. METHODS: Using the French nationwide administrative hospital discharge database, we compared projected numbers and proportions of AVR and hospital outcomes, obtained using linear regressions derived from 2015-2019 trends, with those observed in 2020. RESULTS: In 2020, 21,382 AVRs were performed (13,051 TAVRs, 5706 isolated SAVRs and 2625 SAVRs combined with other cardiac surgery). Compared with the 2020 projected number of AVRs (24,586, 95% confidence interval [CI] 23,525-25,646), TAVRs (14,866, 95% CI 14,164-15,568), isolated SAVRs (6652, 95% CI 6203-7100) and SAVRs combined with other cardiac surgery (3069, 95% CI 2822-3315), there were reductions of 13.0%, 12.2%, 14.2% and 14.5%, respectively. These trends were similar regardless of sex or age. In 2020, the mean age, Charlson Comorbidity Index and hospital admission duration continued to decline, and the proportion of females remained constant, following 2015-2019 trends. Overall, 2020 in-hospital mortality was higher than projected (2.0% observed vs. 1.7% projected; 95% CI 1.5-1.9%), with no increased pacemaker implantation, but more acute kidney injury and cerebrovascular accidents in some surgical subsets. CONCLUSIONS: During the COVID-19 pandemic, fewer TAVR and SAVR procedures were performed, with increased in-hospital mortality and periprocedural complications. Extended follow-up will be important to establish the long-term effect of the COVID-19 pandemic on patient management and outcomes.

TRI-SCORE: a new risk score for in-hospital mortality prediction after isolated tricuspid valve surgery.

AIMS: Isolated tricuspid valve surgery (ITVS) is considered to be a high-risk procedure, but in-hospital mortality is markedly variable. This study sought to develop a dedicated risk score model to predict the outcome of patients after ITVS for severe tricuspid regurgitation (TR). METHODS AND RESULTS: All consecutive adult patients who underwent ITVS for severe non-congenital TR at 12 French centres between 2007 and 2017 were included. We identified 466 patients (60 ± 16 years, 49% female, functional TR in 49%). In-hospital mortality rate was 10%. We derived and internally validated a scoring system to predict in-hospital mortality using multivariable logistic regression and bootstrapping with 1000 re-samples. The final risk score ranged from 0 to 12 points and included eight parameters: age ≥70 years, New York Heart Association Class III-IV, right-sided heart failure signs, daily dose of furosemide ≥125 mg, glomerular filtration rate <30 mL/min, elevated bilirubin, left ventricular ejection fraction <60%, and moderate/severe right ventricular dysfunction. Tricuspid regurgitation mechanism was not an independent predictor of outcome. Observed and predicted in-hospital mortality rates increased from 0% to 60% and from 1% to 65%, respectively, as the score increased from 0 up to ≥9 points. Apparent and bias-corrected areas under the receiver operating characteristic curves were 0.81 and 0.75, respectively, much higher than the logistic EuroSCORE (0.67) or EuroSCORE II (0.63). CONCLUSION: We propose TRI-SCORE as a dedicated risk score model based on eight easy to ascertain parameters to inform patients and physicians regarding the risk of ITVS and guide the clinical decision-making process of patients with severe TR, especially as transcatheter therapies are emerging (www.tri-score.com).

Isolated tricuspid valve surgery: impact of aetiology and clinical presentation on outcomes.

AIMS: The aim of this study was to identify determinants of in-hospital and mid-term outcomes after isolated tricuspid valve surgery (ITVS) and more specifically the impact of tricuspid regurgitation (TR) mechanism and clinical presentation. METHODS AND RESULTS: Among 5661 consecutive adult patients who underwent a tricuspid valve (TV) surgery at 12 French tertiary centres in 2007-2017 collected from a mandatory administrative database, we identified 466 patients (8% of all tricuspid surgeries) who underwent an ITVS. Most patients presented with advanced disease [47% in New York Heart Association (NYHA) III/IV, 57% with right-sided heart failure (HF) signs]. Tricuspid regurgitation was functional in 49% (22% with prior left-sided heart valve surgery and 27% isolated) and organic in 51% (infective endocarditis in 31% and other causes in 20%). In-hospital mortality and major complications rates were 10% and 31%, respectively. Rates of survival and survival free of HF readmission were 75% and 62% at 5 years. Patients with functional TR incurred a worse in-hospital mortality than those with organic TR (14% vs. 6%, P = 0.004), but presentation was more severe. Independent determinants of outcomes were NYHA Class III/IV [odd ratios (OR) = 2.7 (1.2-6.1), P = 0.01], moderate/severe right ventricular dysfunction [OR = 2.6 (1.2-5.8), P = 0.02], lower prothrombin time [OR = 0.98 (0.96-0.99), P = 0.008], and with borderline statistical significance, right-sided HF signs [OR = 2.4 (0.9-6.5), P = 0.06] while TR mechanism was not [OR = 0.7 (0.3-1.8), P = 0.88]. CONCLUSION: Isolated TV surgery was associated with high mortality and morbidity, both in hospital and during follow-up, predicted by the severity of the presentation but not by TR mechanism. Our results suggest that TV intervention should be performed earlier in the course of the disease.

Epicardial adipose tissue volume is associated with left ventricular remodelling in calcific aortic valve stenosis.

BACKGROUND: The severity of left ventricular (LV) remodelling is only partially related to the severity of aortic valve stenosis; additional factors, including diabetes, insulin resistance, obesity and metabolic syndrome, may play important roles. Epicardial adipose tissue (EAT), now considered as a metabolically active organ, is also linked to these factors. AIM: To analyse the association between EAT volume measured using computed tomography and LV remodelling in a prospective cohort of patients with aortic stenosis. METHODS: Consecutive asymptomatic patients with at least mild degenerative aortic stenosis enrolled in a prospective cohort that aimed to assess the determinants of aortic stenosis occurrence and progression constituted our population. RESULTS: We enrolled 143 patients (78±5 years; 65% men). Mean LV mass and EAT volume were 219±64g and 134±56mL, respectively. LV hypertrophy was diagnosed in 86 patients (60%), and concentric hypertrophy (32%) was the main remodelling pattern. EAT was associated with body mass index (P<0.001) and body surface area (P<0.001), but not with age (P=0.33) or aortic stenosis severity (all P>0.10). EAT was correlated with LV mass (r=0.41; P<0.0001), and after adjustment for age, sex, body mass index/body surface area, hypertension, waist circumference, low-density lipoprotein cholesterol and aortic stenosis severity, EAT was independently associated with LV mass (P=0.01/P=0.02). Similar results were found when EAT and LV mass index (adjusted for body surface area) were considered instead of absolute values (P=0.04). CONCLUSIONS: In this prospective cohort of patients with aortic stenosis, EAT volume was independently associated with LV mass. Further studies are warranted to elucidate the underlying mechanisms of this link.

Computed Tomography Aortic Valve Calcium Scoring in Patients With Aortic Stenosis.

BACKGROUND: Computed tomography aortic valve calcium scoring (CT-AVC) holds promise for the assessment of patients with aortic stenosis (AS). We sought to establish the clinical utility of CT-AVC in an international multicenter cohort of patients. METHODS AND RESULTS: Patients with AS who underwent ECG-gated CT-AVC within 3 months of echocardiography were entered into an international, multicenter, observational registry. Optimal CT-AVC thresholds for diagnosing severe AS were determined in patients with concordant echocardiographic assessments, before being used to arbitrate disease severity in those with discordant measurements. In patients with long-term follow-up, we assessed whether CT-AVC thresholds predicted aortic valve replacement and death. In 918 patients from 8 centers (age, 77±10 years; 60% men; peak velocity, 3.88±0.90 m/s), 708 (77%) patients had concordant echocardiographic assessments, in whom CT-AVC provided excellent discrimination for severe AS (C statistic: women 0.92, men 0.89). Our optimal sex-specific CT-AVC thresholds (women 1377 Agatston unit and men 2062 Agatston unit) were nearly identical to those previously reported (women 1274 Agatston unit and men 2065 Agatston unit). Clinical outcomes were available in 215 patients (follow-up 1029 [126-2251] days). Sex-specific CT-AVC thresholds independently predicted aortic valve replacement and death (hazard ratio, 3.90 [95% confidence interval, 2.19-6.78]; P<0.001) after adjustment for age, sex, peak velocity, and aortic valve area. Among 210 (23%) patients with discordant echocardiographic assessments, there was considerable heterogeneity in CT-AVC scores, which again were an independent predictor of clinical outcomes (hazard ratio, 3.67 [95% confidence interval, 1.39-9.73]; P=0.010). CONCLUSIONS: Sex-specific CT-AVC thresholds accurately identify severe AS and provide powerful prognostic information. These findings support their integration into routine clinical practice. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01358513, NCT02132026, NCT00338676, NCT00647088, NCT01679431.

Ascending aorta dilatation rates in patients with tricuspid and bicuspid aortic stenosis: the COFRASA/GENERAC study.

Background: Ascending aorta (AA) dilatation is common in aortic valve stenosis (AS) but data regarding AA progression, its determinants and impact of valve anatomy [bicuspid (BAV), or tricuspid (TAV)] are scarce. Methods and Results: Asymptomatic AS patients enrolled in a prospective cohort (COFRASA/GENERAC) with at least 2 years of follow-up were considered in the present analysis. A transthoracic echocardiography (TTE) and a computed tomography (CT) scan were performed at inclusion and yearly thereafter. We enrolled 195 patients [mean gradient 22 ± 11 mmHg, 42 BAV patients (22%)]. Mean aorta diameters assessed using TTE were 35 ± 4 and 36 ± 5 mm at the sinuses of Valsalva and tubular level, respectively. Ascending aorta diameter was >40 mm in 29% of patients (24% in TAV vs. 52% in BAV, P < 0.01). Determinants of AA diameters were age, sex, BSA, and BAV, but not AS severity. After a mean follow-up of 3.8 ± 1.5years, AA enlargement rate assessed using TTE was +0.18 ± 0.34 mm/year and +0.36 ± 0.54 mm/year at the Valsalva and tubular level, respectively. Determinants of the progression of AA size were smaller AA diameter (P < 0.01) but not baseline AS severity or valve anatomy (all P > 0.05). Only four patients presented an AA progression ≥2 mm/year. Correlations between TTE and CT scan were excellent (all r >0.74) and similar results were obtained using CT. During follow-up, two BAV patients underwent a combined AA surgery; no surgery was primarily performed for AA aneurysm and no dissection was observed. Conclusion: In this prospective cohort of AS patients determinants of AA diameters were age, sex, BSA, and valve anatomy but not AS severity. AA progression rates were low and not influenced by AS severity or valve anatomy.

Influence of metabolic syndrome and diabetes on progression of calcific aortic valve stenosis.

BACKGROUND: Determinants of the progression of aortic stenosis (AS) remained unclear. Metabolic syndrome (MetS) and diabetes are suspected to play an active role but literature is scarce and results conflicting. We sought to assess their impact in an ongoing prospective cohort of asymptomatic patients with at least mild AS. METHODS: We enrolled 203 patients (73±9years, 75% men) with at least 2years of follow-up. Risk-factors assessment was performed at baseline. Annual progression was calculated as [(final-baseline measurements)/follow-up duration] for both mean pressure gradient (MPG) and degree of aortic valve calcification (AVC) measurements. RESULTS: Ninety-nine patients (49%) had MetS and 50 (25%) had diabetes (including 39 with MetS). After a mean follow-up of 3.2±1.2years, AS progression was not different between patients with and without MetS either using MPG (+3±3 vs. +4±4mmHg/year, p=0.25) or AVC (+211±231 vs. +225±222AU/year, p=0.75). Same results were obtained for patients with diabetes (3±3 vs. 4±4mmHg/year p=0.53, 187±140 vs. 229±248AU/year p=0.99). MetS had no impact on AS progression in all tested subgroups based on age, statin prescription, valve anatomy and AS severity (all p≥0.10). CONCLUSION: In our prospective cohort of AS patients, we found no impact of MetS or diabetes on AS progression. Although MetS and diabetes should be actively treated, no impact on AS progression should be expected. Our results support the theory that if cardiovascular risk-factors may play a role at the early phase of AS disease they have no or limited influence on AS progression.

Anatomical features of acute mitral valve repair dysfunction: Additional value of three-dimensional echocardiography.

Recurrence of mitral regurgitation after mitral valve repair is correlated with unfavourable left ventricular remodelling and poor outcome. This pictorial review describes the echocardiographic features of three types of acute mitral valve repair dysfunction, and the additional value of three-dimensional echocardiography.

Determinants and prognostic value of Galectin-3 in patients with aortic valve stenosis.

OBJECTIVE: Myocardial fibrosis has been proposed as an outcome predictor in asymptomatic patients with severe aortic stenosis (AS) that may lead to consider prophylactic surgery. It can be detected using MRI but its widespread use is limited and development of substitute biomarkers is highly desirable. We analysed the determinants and prognostic value of galectin-3, one promising biomarker linked to myocardial fibrosis. METHODS: Patients with at least mild degenerative AS enrolled between 2006 and 2013 in two ongoing studies, COFRASA/GENERAC (COhorte Française de Rétrécissement Aortique du Sujet Agé/GENEtique du Rétrécissement Aortique), aiming at assessing the determinants of AS occurrence and progression, constituted our population. RESULTS: We prospectively enrolled 583 patients. The mean galectin-3 value was 14.3±5.6 ng/mL. There was no association between galectin-3 and functional status (p=0.55) or AS severity (p=0.58). Independent determinants of galectin-3 were age (p=0.0008), female gender (p=0.04), hypertension (p=0.002), diabetes (p=0.02), reduced left ventricular ejection fraction (p=0.01), diastolic dysfunction (E/e', p=0.02) and creatinine clearance (p<0.0001). Among 330 asymptomatic patients at baseline, galectin-3 was neither predictive of outcome in univariate analysis (p=0.73), nor after adjustment for age, gender, rhythm, creatinine clearance and AS severity (p=0.66). CONCLUSIONS: In a prospective cohort of patients with a wide range of AS severity, galectin-3 was not associated with AS severity or functional status. Main determinants of galectin-3 were age, hypertension and renal function. Galectin-3 did not provide prognostic information on the occurrence of AS-related events. Our results do not support the use of galectin-3 in the decision-making process of asymptomatic patients with AS. TRIAL REGISTRATION NUMBER: COFRASA NCT00338676 and GENERAC CT00647088.

The effect of residents as teaching assistants on operative time in laparoscopic cholecystectomy.

BACKGROUND: We examined the effect of primary surgeon (PS) and teaching assistant (TA) seniority on operative time and outcomes for residents performing laparoscopic cholecystectomy (LC). METHODS: This was a retrospective analysis of urgent LC at a county teaching hospital. Relevant data included postgraduate year (PGY) of the PS and TA and markers of disease severity. Primary outcome was operative time. Secondary outcomes were conversion to open cholecystectomy and complications. RESULTS: There were 1,202 LCs; 415 included an intraoperative cholangiogram. On multivariable analysis, every PGY increase of PS decreased operative time by 3.2 minutes (P = .02). For every PGY increase of TA, operative time decreased 10.8 minutes (P < .001). Acute or gangrenous pathology increased conversion to open surgery (P < .001). Seniority of PS and TA was not associated with increases in conversion or complication rates. CONCLUSIONS: Residents' operative time improves as experience with LC increases. These improvements become more profound after adjusting for the seniority of the TA.

Increased use of brachiocephalic arteriovenous fistulas improves functional primary patency.

OBJECTIVE: As vascular surgeons strive to meet the Fistula First Initiative, some authors have observed a decrease in arteriovenous fistula (AVF) maturation rates in association with an increase in AVF creation. In May 2012, we adopted a practice change in an attempt to maintain the same high level of AVF creation while leading to a decrease in fistula failures. METHODS: A retrospective study was conducted of all dialysis access procedures performed by a single vascular surgeon before (period 1; before May 1, 2012) and after (period 2; after May 1, 2012) the change in practice pattern. The adopted change included favoring the brachiocephalic location unless the patient was an ideal anatomic candidate for a radiocephalic AVF, creating a larger and standardized arteriotomy, and using a large venous footplate whenever possible. The main outcome measure was primary functional patency at 1 year. Secondary outcome measures included primary patency at 1 year, time to maturation, type of fistula created, steal syndrome, and tunneled hemodialysis catheter infections. RESULTS: Of 213 vascular access procedures performed, 191 (90%) were AVFs. There was no difference in use of AVFs between period 1 (93% AVFs) and period 2 (88% AVFs; P = .2). Use of brachiocephalic AVFs increased from 38% in period 1 to 56% in period 2 (P = .01), with a corresponding trend toward a decrease in radiocephalic AVFs in period 2 (36% in period 1 to 27% in period 2; P = .2). Primary functional patency at 1 year was 47% in period 1 and 63% in period 2 (P = .03). Primary patency at 1 year was 51% in period 1 and 70% in period 2 (P = .001). Time to reach functional maturation was decreased in period 2 (median, 76 vs 82.5 days; P = .046). There was no difference in steal syndrome (P = 1.0), and the incidence of hemodialysis catheter infections was lower in period 2 (0 vs 7 [7%]; P = .006). CONCLUSIONS: Increasing brachiocephalic AVF creation and reducing our reliance on radiocephalic AVFs resulted in a significant increase in primary functional patency at 1 year. This was achieved while maintaining the same high percentage of fistulas, a lower rate of central catheter infections, and the same low incidence of steal syndrome.

Variation in the learning curves of general surgery residents performing arteriovenous fistulas.

BACKGROUND: An arteriovenous fistula (AVF), performed for hemodialysis access, provides one of the few remaining opportunities for general surgery residents to perform an open vascular anastomosis (VA). Limited data exist regarding the learning curve of residents performing this procedure. The objective of this study was to determine how residents improve in performance of VA by implementing real-time tracking of anastomosis time as well as technical errors. STUDY DESIGN: From April 2012 to January 2014, we conducted a prospective intraoperative assessment of 9 postgraduate year 3 general surgery residents during the performance of AVFs using a checklist of common errors in VA. Time for AVF anastomosis completion and number and types of technical errors during anastomosis were recorded. Primary end points were the change in anastomosis time and change in technical errors over time. RESULTS: A total of 86 AVFs were performed and assessed intraoperatively. Each resident performed a median of 10 AVFs (interquartile range [IQR]: 7-11). The mean anastomosis time was 18.1 minutes. The mean number of technical errors was 13.8 per case. Overall, for every additional AVF performed, mean anastomosis time decreased by 0.63 minutes (95% CI: 0.45-0.81, p < 0.0001) and the mean number of technical errors decreased by 1.0 (95% CI: 0.7-1.3, p < 0.0001). The greatest improvement in overall errors (mean difference = 7.9, p = 0.03) and time (mean difference = 4.7min, p = 0.03) occurred after the performance of 3 AVFs. However, when analyzed by individual resident, the R(2) value for anastomotic time by number of AVFs performed ranged from 0.01 to 0.69. Similarly, for technical errors, the R(2) value by number of AVFs performed ranged from 0.04 to 0.62. CONCLUSIONS: In novice surgical residents performing AVFs, improvement in VA skill can readily be tracked via anastomosis time and technical errors. Collectively, there is a strong association between number of cases performed and reduction in time and errors. However, individually, the number of cases completed did not correlate well with time and errors. These findings suggest that for VA skills, determining progression from novice to competence cannot rely on case volume but rather needs to be individualized.

Haemodynamic and anatomic progression of aortic stenosis.

BACKGROUND: Aortic valve stenosis (AS) is a progressive disease, but the impact of baseline AS haemodynamic or anatomic severity on AS progression remains unclear. METHODS: In 149 patients (104 mild AS, 36 moderate AS and 9 severe AS) enrolled in 2 ongoing prospective cohorts (COFRASA/GENERAC), we evaluated AS haemodynamic severity at baseline and yearly, thereafter, using echocardiography (mean pressure gradient (MPG)) and AS anatomic severity using CT (degree of aortic valve calcification (AVC)). RESULTS: After a mean follow-up of 2.9±1.0 years, mean MGP increased from 22±11 to 30±16 mm Hg (+3±3 mm Hg/year), and mean AVC from 1108±891 to 1640±1251 AU (arbitrary units) (+188±176 AU/year). Progression of AS was strongly related to baseline haemodynamic severity (+2±3 mm Hg/year in mild AS, +4±3 mm Hg/year in moderate AS and +5±5 mm Hg/year in severe AS (p=0.01)), and baseline haemodynamic severity was an independent predictor of haemodynamic progression (p=0.0003). Annualised haemodynamic and anatomic progression rates were significantly correlated (r=0.55, p<0.0001), but AVC progression rate was also significantly associated with baseline haemodynamic severity (+141±133 AU/year in mild AS, +279±189 AU/year in moderate AS and +361±293 AU/year in severe AS, p<0.0001), and both baseline MPG and baseline AVC were independent determinants of AVC progression (p<0.0001). CONCLUSIONS: AS progressed faster with increasing haemodynamic or anatomic severity. Our results suggest that a medical strategy aimed at preventing AVC progression may be useful in all subsets of patients with AS including those with severe AS and support the recommended closer follow-up of patients with AS as AS severity increases. CLINICAL TRIAL REGISTRATION: COFRASA (clinicalTrial.gov number NCT 00338676) and GENERAC (clinicalTrial.gov number NCT00647088).

Can it wait until morning? A comparison of nighttime versus daytime cholecystectomy for acute cholecystitis.

BACKGROUND: The urgency of laparoscopic cholecystectomy for acute cholecystitis is under debate. We hypothesized that nighttime cholecystectomy is associated with decreased length of stay. METHODS: Retrospective review of 1,140 patients at 2 large urban referral centers with acute cholecystitis who underwent daytime (7 am to 7 pm) versus nighttime (7 pm to 7 am) cholecystectomy was conducted. RESULTS: Nighttime cholecystectomy did not affect the overall length of stay (3.7 vs 3.8 days, P = .08) or complication rate (5% vs 7%, P = .5) versus daytime cholecystectomy. Nighttime cholecystectomy was associated with a higher conversion rate to open cholecystectomy (11% vs 6%, P = .008). On multivariable analysis, independent predictors of conversion to open surgery were nighttime cholecystectomy, age, and gangrenous cholecystitis (P = .01). The only predictor of complications was gangrenous cholecystitis (P = .02). CONCLUSIONS: Nighttime cholecystectomy is associated with an increased conversion to open surgery without decrease in length of stay or complications. These findings suggest that laparoscopic cholecystectomy for acute cholecystitis should be delayed until normal working hours.

Factors associated with general surgery residents' desire to leave residency programs: a multi-institutional study.

IMPORTANCE: General surgical residency continues to experience attrition. To date, work hour amendments have not changed the annual rate of attrition. OBJECTIVE: To determine how often categorical general surgery residents seriously consider leaving residency. DESIGN, SETTING, AND PARTICIPANTS: At 13 residency programs, an anonymous survey of 371 categorical general surgery residents and 10-year attrition rates for each program. Responses from those who seriously considered leaving surgical residency were compared with those who did not. MAIN OUTCOMES AND MEASURES: Factors associated with the desire to leave residency. RESULTS: The survey response rate was 77.6%. Overall, 58.0% seriously considered leaving training. The most frequent reasons for wanting to leave were sleep deprivation on a specific rotation (50.0%), an undesirable future lifestyle (47.0%), and excessive work hours on a specific rotation (41.4%). Factors most often cited that kept residents from leaving were support from family or significant others (65.0%), support from other residents (63.5%), and perception of being better rested (58.9%). On univariate analysis, older age, female sex, postgraduate year, training in a university program, the presence of a faculty mentor, and lack of Alpha Omega Alpha status were associated with serious thoughts of leaving surgical residency. On multivariate analysis, only female sex was significantly associated with serious thoughts of leaving residency (odds ratio, 1.2; 95% CI, 1.1-1.3; P = .003). Eighty-six respondents were from historically high-attrition programs, and 202 respondents were from historically low-attrition programs (27.8% vs 8.4% 10-year attrition rate, P = .04). Residents from high-attrition programs were more likely to seriously consider leaving residency (odds ratio, 1.8; 95% CI, 1.0-3.0; P = .03). CONCLUSIONS AND RELEVANCE: A majority of categorical general surgery residents seriously consider leaving residency. Female residents are more likely to consider leaving. Thoughts of leaving seem to be associated with work conditions on specific rotations rather than with overall work hours and are more prevalent among programs with historically high attrition rates.

Kuppfer cells trigger nonalcoholic steatohepatitis development in diet-induced mouse model through tumor necrosis factor-α production.

BACKGROUND: The mechanisms triggering nonalcoholic steatohepatitis (NASH) remain poorly defined. RESULTS: Kupffer cells are the first responding cells to hepatocyte injuries, leading to TNFα production, chemokine induction, and monocyte recruitment. The silencing of TNFα in myeloid cells reduces NASH progression. CONCLUSION: Increase of TNFα-producing Kupffer cells is crucial for triggering NASH via monocyte recruitment. SIGNIFICANCE: Myeloid cells-targeted silencing of TNFα might be a tenable therapeutic approach. Nonalcoholic steatohepatitis (NASH), characterized by lipid deposits within hepatocytes (steatosis), is associated with hepatic injury and inflammation and leads to the development of fibrosis, cirrhosis, and hepatocarcinoma. However, the pathogenic mechanism of NASH is not well understood. To determine the role of distinct innate myeloid subsets in the development of NASH, we examined the contribution of liver resident macrophages (i.e. Kupffer cells) and blood-derived monocytes in triggering liver inflammation and hepatic damage. Employing a murine model of NASH, we discovered a previously unappreciated role for TNFα and Kupffer cells in the initiation and progression of NASH. Sequential depletion of Kupffer cells reduced the incidence of liver injury, steatosis, and proinflammatory monocyte infiltration. Furthermore, our data show a differential contribution of Kupffer cells and blood monocytes during the development of NASH; Kupffer cells increased their production of TNFα, followed by infiltration of CD11b(int)Ly6C(hi) monocytes, 2 and 10 days, respectively, after starting the methionine/choline-deficient (MCD) diet. Importantly, targeted knockdown of TNFα expression in myeloid cells decreased the incidence of NASH development by decreasing steatosis, liver damage, monocyte infiltration, and the production of inflammatory chemokines. Our findings suggest that the increase of TNFα-producing Kupffer cells in the liver is crucial for the early phase of NASH development by promoting blood monocyte infiltration through the production of IP-10 and MCP-1.

Complications of arthroscopic meniscectomy in the older population.

BACKGROUND: Complications of arthroscopic meniscectomy in the older population have not been established. PURPOSE: To determine the risk and relative risk of developing pyogenic arthritis (PA), a deep vein thrombosis (DVT), and pulmonary embolism (PE) in an older population of patients who have undergone arthroscopic meniscectomy. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Men and women ≥65 years old who underwent procedures coded as CPT-29880 (medial and lateral meniscectomy) and CPT-29881 (medial or lateral meniscectomy) were identified in the Medicare Standard Analytic Files database from 2005 to 2008. Identified patients were analyzed for gender and postoperative complications, including PA, DVT, and PE, occurring within 90 days of the index operation. RESULTS: Overall, 314,578 patients (119,814 men and 194,764 women) were identified. With respect to the Current Procedural Terminology codes, 131,420 patients were coded 29880 and 183,158 patients were coded 29881. In the study population, 0.4% (1107 patients) developed PA, 0.8% (2507 patients) developed a DVT, and 0.3% (982 patients) developed a PE. Among male patients, 0.4% developed PA, 0.7% developed a DVT, and 0.2% developed a PE. Among female patients, 0.3% developed PA, 0.8% developed a DVT, and 0.3% developed a PE. Overall, men had a statistically significant higher relative risk of PA and women had a statistically significant higher relative risk of DVT and PE. CONCLUSION: Postoperative complications, including PA, DVTs, and PEs, are rare in patients ≥65 years old. However, gender-specific differences in the rate and type of postoperative complications may exist. Further studies in this population are warranted.

Distribution of prolactin receptors suggests an intraductal role for prolactin in the mouse and human mammary gland, a finding supported by analysis of signaling in polarized monolayer cultures.

Despite the important role of prolactin (PRL) in mammary gland development and function, little is known about the distribution of the different forms of the prolactin receptor (PRLR) under various physiological circumstances. Here, the distribution of the long (LF) and the short (S3 in mouse) receptor common to both mice and rats was determined by immunofluorescence on frozen sections of virgin, pregnant and lactating mouse mammary gland. Myoepithelial cells were consistently and intensely stained for both receptors. For luminal cells at all stages (ducts and alveoli), a large proportion of PRLR staining was unexpectedly present on the apical face. In the non-lactating state, no basal staining of luminal cells was detectable. During lactation, a proportion of both receptors moved to the basolateral surface. In vitro, HC11 cells showed constitutive expression of LF but expression of S3 only upon the formation of adherent junctions. Tight junction formation was accelerated by incubation in pseudo-phosphorylated PRL, as measured by transepithelial resistance and the expression and placement of the tight junction protein, zonula occludens-1. Once an intact monolayer had formed, all LF and S3 receptors were apical (akin to the non-lactating state) and only apical application of PRL activated the Jak2-STAT5 and ERK pathways. By contrast, basolateral application of PRL resulted in a reduction in basal ERK phosphorylation, suggesting an involvement of a dual specificity protein phosphatase. Normal human breast samples also showed apical PRLRs. These results demonstrate important contextual aspects of PRL-PRLR interactions with implications for the analysis of the role of PRL in breast cancer.

The "50% rule" in arthroscopic and orthopaedic surgery.

The "50% rule" is used commonly to guide treatment of partial tears of tendons and ligaments. The purpose of this study was to examine the history and validity of the 50% rule in arthroscopic and orthopaedic surgery. A PubMed search yielded 1,039 articles that were reviewed to identify the origins of the 50% rule for hand flexor tendon lacerations, partial anterior cruciate ligament tears, partial-thickness rotator cuff tears, and partial injuries of the long head of the biceps tendon. The rule appears to have evolved from the hand literature toward somewhat arbitrary application for other orthopaedic conditions. Little scientific information is available to support the 50% rule for these disparate entities. In our Level V opinion, the 50% rule allows surgeons to use subjective discretion in the management of prevalent orthopaedic conditions but there is very little scientific support for this ubiquitous decision-making criterion.