Interdisciplinary management of Type 3 oligodontia: A retrospective case series.

STATEMENT OF PROBLEM: Type 3 oligodontia is the most dentoalveolar deficient manifestation of congenital tooth absence. There is a need to rehabilitate these children functionally and esthetically to improve quality of life. PURPOSE: The purpose of this retrospective case series was to evaluate the short- and intermediate-term outcomes of the dental treatment provided in a children's hospital and to develop a sequential interdisciplinary treatment planning protocol from infancy to the completion of jaw development. MATERIAL AND METHODS: A total of 10 patients were included in this retrospective longitudinal case series report. Different interventions had been carried out at times related to growth and development of the jaws. Implant-supported fixed dental prostheses were provided after the lateral growth of the anterior mandible had stabilized at around 12 years of age. Definitive mandibular prostheses were provided after the cessation of growth and following maxillary treatment. Treatment for the maxilla was more complex. Bone grafted and graftless implant-supported fixed prostheses were offered as alternatives to a complete denture. Implant stability and soft tissue response were evaluated at prosthesis removal. RESULTS: Seven patients received a 4-implant and 2 a 5-implant-supported immediately loaded fixed mandibular prosthesis. One patient elected to maintain the interim complete denture. Of the 38 implants, 2 failed and were satisfactorily replaced. In the maxilla, 4 patients elected to maintain a complete denture, and 6 received a maxillary implant-supported fixed prosthesis: 1 with bilateral sinus lift bone grafting and 6 regular implants; 1 with 6 regular implants; 1 with 4 regular implants; 2 with bilateral zygoma implants plus 2 regular anterior implants; and 1 with 4 zygoma implants. No implant failures were recorded in the maxilla. Follow-up for mandibular treatment ranged from 1 to 12 years and for maxillary treatment 1 to 9 years. All implants were classified as asymptomatic and surviving. CONCLUSIONS: The use of fixed implant-supported prostheses in selected individuals with Type 3 oligodontia can improve functional and esthetic outcomes as compared with the use of removable prostheses alone. Implant-supported prostheses require an interdisciplinary approach from early childhood until growth cessation.

In-Hospital and 1-Year Clinical Results from the French Registry Using Polymer-Free Sirolimus-Eluting Stents in Acute Coronary Syndrome and Stable Coronary Artery Disease.

Objectives: The aim of this postmarket clinical study was to assess the safety and efficacy of the latest generation polymer-free sirolimus-eluting stents (PF-SES) in an all-comers population comparing outcomes in stable coronary artery disease (CAD) versus acute coronary syndrome (ACS) in France. Background: The efficacy and safety of the first-generation PF-SES have already been demonstrated by randomized controlled trials and "all-comers" observational studies. Methods: For this all-comers observational, prospective, multicenter study, 1456 patients were recruited in 22 French centers. The primary endpoint was target lesion revascularization (TLR) rate at 12 months and secondary endpoints included major adverse cardiac events (MACE) and bleeding. Results: 895 patients had stable CAD and 561 had ACS. At 12 months, 2% of patients had a TLR, with similar rates between stable CAD and ACS (1.9% vs 2.2%, p = 0.7). The overall MACE rate was 5.2% with an expected higher rate in patients with ACS as compared to those with stable CAD (7.3% vs 3.9%, p = 0.007). The overall bleeding event rate was 4.5%, with similar rates in stable CAD as compared to ACS patients (3.8% vs 5.6%, p = 0.3). Dual antiplatelet therapy (DAPT) interruptions prior to the recommended duration occurred in 41.7% of patients with no increase in MACE rates as compared to patients who did not prematurely interrupt DAPT (3.9% vs 6.1%, p = 0.073). Conclusions: The latest generation PF-SES is associated with low clinical event rates in these all-comers patients. There was a high rate of prematurely terminated DAPT, without any effect on MACE at 12 months. This trial is registered with NCT03809715.

Safety and incremental prognostic value of stress cardiovascular magnetic resonance in patients with known chronic kidney disease.

BACKGROUND: Cardiovascular disease (CVD) is the main cause of mortality in patients with chronic kidney disease (CKD). Although several studies have demonstrated the consistently high prognostic value of stress cardiovascular magnetic resonance (CMR), its prognostic value in patients with CKD is not well established. We aimed to assess the safety and the incremental prognostic value of vasodilator stress perfusion CMR in consecutive symptomatic patients with known CKD. METHODS: Between 2008 and 2021, we conducted a retrospective dual center study with all consecutive symptomatic patients with known stage 3 CKD, defined by estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73 m2, referred for vasodilator stress CMR. All patients with eGFR < 30 ml/min/1.73 m2 (n = 62) were excluded due the risk of nephrogenic systemic fibrosis. All patients were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or recurrent nonfatal myocardial infarction (MI). Cox regression analysis was used to determine the prognostic value of stress CMR parameters. RESULTS: Of 825 patients with known CKD (71.4 ± 8.8 years, 70% men), 769 (93%) completed the CMR protocol. Follow-up was available in 702 (91%) (median follow-up 6.4 (4.0-8.2) years). Stress CMR was well tolerated without occurrence of death or severe adverse event related to the injection of gadolinium or cases of nephrogenic systemic fibrosis. The presence of inducible ischemia was associated with the occurrence of MACE (hazard ratio [HR] 12.50; 95% confidence interval [CI] 7.50-20.8; p < 0.001). In multivariable analysis, ischemia and late gadolinium enhancement were independent predictors of MACE (HR 15.5; 95% CI 7.72 to 30.9; and HR 4.67 [95% CI 2.83-7.68]; respectively, both p < 0.001). After adjustment, stress CMR findings showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.13; NRI = 0.477; IDI = 0.049). CONCLUSIONS: In patients with known stage 3 CKD, stress CMR is safe and its findings have an incremental prognostic value to predict MACE over traditional risk factors.

Literature review on the use of methoxyflurane in the management of pain in cancer-related procedures.

INTRODUCTION: Self-administered methoxyflurane, also known as Penthrox, at a sub-anesthetic dose is a short-term, fast-acting, and safe analgesic that may provide suitable pain relief for cancer patients. This review aims to compile the existing evidence on methoxyflurane and its efficacy in reducing pain during cancer-related procedures. METHODS: A literature search was conducted through OVID Medline and Embase. The search was limited to articles published between 2012 and 2021 and studies were included if they assessed the efficacy of methoxyflurane to reduce pain in cancer-related procedures. All types of cancer were included. RESULTS: The literature search yielded seven studies published between 2012 and 2021. The studies analyzed assessed methoxyflurane use in prostate biopsy, colonoscopy, removal of brachytherapy rods, and bone marrow biopsy. Various research designs were employed, including three randomized controlled trials, two prospective observational studies, one retrospective, and one non-randomized controlled trial. In all, methoxyflurane has a demonstrated ability to reduce pain in these procedures. CONCLUSION: In the limited studies available in evaluating the efficacy of methoxyflurane for reducing procedural pain during cancer-related procedures, all have demonstrated clinical equivalency or superiority. Pain relief appears to be equivalent however methoxyflurane overcomes the standard limitations of respiratory sedation and has demonstrated quicker procedural recovery times than traditional sedation methods. The accumulated data to date supports the use of methoxyflurane which can supplement or supplant current methods of analgesia in cancer-related procedures.

Analytic Morphomics in Myositis-Related Interstitial Lung Disease.

PURPOSE: Interstitial lung disease (ILD) is the most common non-musculoskeletal manifestation of idiopathic inflammatory myopathies (IIM). Identification of body composition change may enable early intervention to improve prognosis. We investigated muscle quantity and quality derived from cross-sectional imaging in IIM, and its relationship to ILD severity. METHODS: A retrospective cohort study assessing IIM of ILD patients (n = 31) was conducted. Two datasets separated in time were collected, containing demographics, biochemical data, pulmonary function testing and thoracic CT data. Morphomic analysis of muscle quantity (cross-sectional area) and quality (density in Hounsfield Units) on thoracic CT were analysed utilising a web-based tool allowing segmentation of muscle and fat. Bilateral erector spinae and pectoralis muscle (ESM&PM) were measured at defined vertebral levels. RESULTS: FVC and DLCO decreased but within acceptable limits of treatment response (FVC: 83.7-78.7%, p < 0.05, DLCO 63.4-60.6%, p < 0.05). The cross-sectional area of the PM and ESM increased (PM: 39.8 to 40.7 cm2, p = 0.491; ESM: 35.2 to 39.5 cm2, p = 0.098). Density significantly fell for both the PM and ESM (PM: 35.3-31 HU, p < 0.05; ESM: 38-33.7, p < 0.05). Subcutaneous fat area increased from 103.9 to 136.1 cm2 (p < 0.05), while the visceral fat area increased but not reaching statistical significance. The change in PM density between time points demonstrated an inverse correlation with DLCO (p < 0.05, R = - 0.49). CONCLUSION: Patients with IIM ILD demonstrated significant body composition changes on CT imaging unlikely to be detected by traditional measurement tools. An increase in muscle area with an inverse decrease in density suggests poor muscle quality.

Establishing a priori and a posteriori predictive models to assess patients' peak skin dose in interventional cardiology. Part 2: results of the VERIDIC project.

BACKGROUND: Optimizing patient exposure in interventional cardiology is key to avoid skin injuries. PURPOSE: To establish predictive models of peak skin dose (PSD) during percutaneous coronary intervention (PCI), chronic total occlusion percutaneous coronary intervention (CTO), and transcatheter aortic valve implantation (TAVI) procedures. MATERIAL AND METHODS: A total of 534 PCI, 219 CTO, and 209 TAVI were collected from 12 hospitals in eight European countries. Independent associations between PSD and clinical and technical dose determinants were examined for those procedures using multivariate statistical analysis. A priori and a posteriori predictive models were built using stepwise multiple linear regressions. A fourfold cross-validation was performed, and models' performance was evaluated using the root mean square error (RMSE), mean absolute percentage error (MAPE), coefficient of determination (R²), and linear correlation coefficient (r). RESULTS: Multivariate analysis proved technical parameters to overweight clinical complexity indices with PSD mainly affected by fluoroscopy time, tube voltage, tube current, distance to detector, and tube angulation for PCI. For CTO, these were body mass index, tube voltage, and fluoroscopy contribution. For TAVI, these parameters were sex, fluoroscopy time, tube voltage, and cine acquisitions. When benchmarking the predictive models, the correlation coefficients were r = 0.45 for the a priori model and r = 0.89 for the a posteriori model for PCI. These were 0.44 and 0.67, respectively, for the CTO a priori and a posteriori models, and 0.58 and 0.74, respectively, for the TAVI a priori and a posteriori models. CONCLUSION: A priori predictive models can help operators estimate the PSD before performing the intervention while a posteriori models are more accurate estimates and can be useful in the absence of skin dose mapping solutions.

Patient exposure dose in interventional cardiology per clinical and technical complexity levels. Part 1: results of the VERIDIC project.

BACKGROUND: Patients can be exposed to high skin doses during complex interventional cardiology (IC) procedures. PURPOSE: To identify which clinical and technical parameters affect patient exposure and peak skin dose (PSD) and to establish dose reference levels (DRL) per clinical complexity level in IC procedures. MATERIAL AND METHODS: Validation and Estimation of Radiation skin Dose in Interventional Cardiology (VERIDIC) project analyzed prospectively collected patient data from eight European countries and 12 hospitals where percutaneous coronary intervention (PCI), chronic total occlusion PCI (CTO), and transcatheter aortic valve implantation (TAVI) procedures were performed. A total of 62 clinical complexity parameters and 31 technical parameters were collected, univariate regressions were performed to identify those parameters affecting patient exposure and define DRL accordingly. RESULTS: Patient exposure as well as clinical and technical parameters were collected for a total of 534 PCI, 219 CTO, and 209 TAVI. For PCI procedures, body mass index (BMI), number of stents ≥2, and total stent length >28 mm were the most prominent clinical parameters, which increased the PSD value. For CTO, these were total stent length >57 mm, BMI, and previous anterograde or retrograde technique that failed in the same session. For TAVI, these were male sex, BMI, and number of diseased vessels. DRL values for Kerma-area product (PKA), air kerma at patient entrance reference point (Ka,r), fluoroscopy time (FT), and PSD were stratified, respectively, for 14 clinical parameters in PCI, 10 in CTO, and four in TAVI. CONCLUSION: Prior knowledge of the key factors influencing the PSD will help optimize patient radiation protection in IC.

Apixaban vs. standard of care after transcatheter aortic valve implantation: the ATLANTIS trial.

AIMS: The respective roles of oral anticoagulation or antiplatelet therapy following transcatheter aortic valve implantation (TAVI) remain debated. ATLANTIS is an international, randomized, open-label, superiority trial comparing apixaban to the standard of care. METHODS AND RESULTS: After successful TAVI, 1500 patients were randomized (1:1) to receive apixaban 5 mg (2.5 mg if impaired renal function or concomitant antiplatelet therapy) (n = 749) twice daily, or standard of care (n = 751). Randomization was stratified by the need for chronic anticoagulation therapy. Standard-of-care patients received a vitamin K antagonist (VKA) (Stratum 1) or antiplatelet therapy (Stratum 2) if there was an indication for anticoagulation or not, respectively. The primary endpoint was the composite of death, myocardial infarction, stroke or transient ischaemic attack, systemic embolism, intracardiac or bioprosthesis thrombosis, deep vein thrombosis or pulmonary embolism, and life-threatening, disabling, or major bleeding over 1-year follow-up. The primary safety endpoint was major, disabling, or life-threatening bleeding. The primary outcome occurred in 138 (18.4%) and 151 (20.1%) patients receiving apixaban or standard of care, respectively [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.73-1.16] and there was no evidence of interaction between treatment and stratum (Pinteraction = 0.57). The primary safety endpoint was similar in both groups (HR 1.02; 95% CI 0.72-1.44). In Stratum 1 (n = 451), an exploratory analysis showed no difference for all endpoints between apixaban and VKA. In Stratum 2 (n = 1049), the primary outcome and primary safety endpoint did not differ, but obstructive valve thrombosis was reduced with apixaban vs. antiplatelet therapy (HR 0.19; 95% CI 0.08-0.46), while a signal of higher non-cardiovascular mortality was observed with apixaban. CONCLUSION: After TAVI, apixaban was not superior to the standard of care, irrespective of an indication for oral anticoagulation.

An answered call for aid? Cannabinoid clinical framework for the opioid epidemic.

BACKGROUND: The opioid crisis continues in full force, as physicians and caregivers are desperate for resources to help patients with opioid use and chronic pain disorders find safer and more accessible non-opioid tools. MAIN BODY: The purpose of this article is to review the current state of the opioid epidemic; the shifting picture of cannabinoids; and the research, policy, and current events that make opioid risk reduction an urgent public health challenge. The provided table contains an evidence-based clinical framework for the utilization of cannabinoids to treat patients with chronic pain who are dependent on opioids, seeking alternatives to opioids, and tapering opioids. CONCLUSION: Based on a comprehensive review of the literature and epidemiological evidence to date, cannabinoids stand to be one of the most interesting, safe, and accessible tools available to attenuate the devastation resulting from the misuse and abuse of opioid narcotics. Considering the urgency of the opioid epidemic and broadening of cannabinoid accessibility amidst absent prescribing guidelines, the authors recommend use of this clinical framework in the contexts of both clinical research continuity and patient care.

Position statement: management of rotator cuff tears in adults.

We sought to compare success and re-tear rates of surgically treated full-thickness tears of the rotator cuff in men and women older than 18 years of age to develop a guideline intended for orthopedic surgeons and other health care providers who assess, counsel and care for these patients. We searched Medline, Embase and Cochrane databases through to Apr. 20, 2021, and included all English-language randomized trials comparing single-row versus double-row fixation via arthroscopic approaches; latissimus dorsi transfer (LDT) versus partial rotator cuff repair, lower trapezius transfer (LTT), and superior capsular reconstruction (SCR); and early versus late arthroscopic rotator cuff repair for traumatic tears. We also considered observational studies comparing LDT with LTT and partial repair and studies comparing early versus late treatment of traumatic rotator cuff tears. Outcomes of interest were functional outcomes, pain outcomes, and re-tear rates associated with these interventions. We rated the quality of the evidence and strength of recommendations using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. This guideline will benefit patients seeking surgical intervention of full thickness rotator cuff tears by improving counselling on surgical treatment options and outcomes. It will also benefit surgical providers by expanding their knowledge of various surgical approaches. Data presented could be used to develop frameworks and tools for shared decision-making.

Ceramide kinase regulates acute wound healing by suppressing 5-oxo-ETE biosynthesis and signaling via its receptor OXER1.

The sphingolipid, ceramide-1-phosphate (C1P), has been shown to promote the inflammatory phase and inhibit the proliferation and remodeling stages of wound repair via direct interaction with group IVA cytosolic phospholipase A2, a regulator of eicosanoid biosynthesis that fine-tunes the behaviors of various cell types during wound healing. However, the anabolic enzyme responsible for the production of C1P that suppresses wound healing as well as bioactive eicosanoids and target receptors that drive enhanced wound remodeling have not been characterized. Herein, we determined that decreasing C1P activity via inhibitors or genetic ablation of the anabolic enzyme ceramide kinase (CERK) significantly enhanced wound healing phenotypes. Importantly, postwounding inhibition of CERK enhanced the closure rate of acute wounds, improved the quality of healing, and increased fibroblast migration via a "class switch" in the eicosanoid profile. This switch reduced pro-inflammatory prostaglandins (e.g., prostaglandin E2) and increased levels of 5-hydroxyeicosatetraenoic acid and the downstream metabolite 5-oxo-eicosatetraenoic acid (5-oxo-ETE). Moreover, dermal fibroblasts from mice with genetically ablated CERK showed enhanced wound healing markers, while blockage of the murine 5-oxo-ETE receptor (oxoeicosanoid receptor 1) inhibited the enhanced migration phenotype of these cell models. Together, these studies reinforce the vital roles eicosanoids play in the wound healing process and demonstrate a novel role for CERK-derived C1P as a negative regulator of 5-oxo-ETE biosynthesis and the activation of oxoeicosanoid receptor 1 in wound healing. These findings provide foundational preclinical results for the use of CERK inhibitors to shift the balance from inflammation to resolution and increase the wound healing rate.

Change in Left Atrioventricular Coupling Index to Predict Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background Left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic values as predictors of atrial fibrillation (AF). Purpose To investigate the prognostic value of a left atrioventricular coupling index (LACI) and average annualized change in LACI (hereafter, ΔLACI) measured by cardiac MRI to predict incident AF in a population-based sample from the Multi-Ethnic Study of Atherosclerosis (MESA). Materials and Methods In a secondary analysis of the prospective MESA, 1911 study participants without clinically recognized AF and cardiovascular disease at baseline had LACI assessed with cardiac MRI at baseline (examination 1, 2000-2002) and 10 years later (examination 5, 2010-2012). LACI was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average ΔLACI with incident AF. Results Among the 1911 participants (mean age, 59 years ± 9 [standard deviation]; 907 men), 87 incident AF events occurred over 3.9 years ± 0.9 after the second imaging (examination 5). After adjustment for traditional risk factors, greater LACI and ΔLACI were independently associated with AF (hazard ratio, 1.69 [95% CI: 1.46, 1.96] and 1.71 [95% CI: 1.50, 1.94], respectively; both P < .001). Adjusted models for LACI and ΔLACI showed improvement in model discrimination compared with currently used AF risk score (Cohort for Heart and Aging Research in Genomic Epidemiology-Atrial Fibrillation, or CHARGE-AF, score) model (area under receiver operating characteristic curve [AUC], 0.78 vs 0.74; and AUC, 0.80 vs 0.74, respectively; both P < .001); and to the final model including individual LA or LV parameters for predicting AF incidence (AUC, 0.78 vs 0.76; and AUC, 0.80 vs 0.78, respectively; both P < .001). Conclusion Atrioventricular coupling (left atrioventricular coupling index [LACI]) and coupling change (annual change in LACI) were strong predictors for atrial fibrillation (AF) in a multiethnic population. Both had incremental prognostic value for predicting AF over traditional risk factors, and superior discrimination compared with the Cohort for Heart and Aging Research in Genomic Epidemiology-Atrial Fibrillation, or CHARGE-AF, score and to individual left atrial or left ventricular parameters. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Leiner in this issue.

Rotator Cuff Injury and Repair.

Rotator cuff pathology is a commonly encountered clinical and radiologic entity that can manifest as tendinopathy or tearing. Magnetic resonance imaging (MRI) and ultrasonography offer similar sensitivity and specificity for the evaluation of the native rotator cuff, and the chosen modality may vary, depending on local practice and accessibility. MR arthrography is frequently used in the postoperative setting as a problem-solving tool. Key findings to include in the preoperative MRI report include the size and location of the tear, thickness of the tendon involved (partial versus full thickness), and overall tendon quality. The report should also address features associated with poor surgical outcomes, such as fatty atrophy, a decreased acromiohumeral interval, and evidence of rotator cuff arthropathy. Musculoskeletal radiologists should be familiar with the various surgical techniques and expected postoperative imaging appearance of rotator cuff repairs. Imaging also plays a role in identifying recurrent tearing, graft failure, hardware loosening, infection, and other complications.

Treatment of rotator cuff tears: a systematic review and meta-analysis.

BACKGROUND: There is ongoing controversy regarding optimal treatment for full-thickness rotator cuff tears. Given that the evidence surrounding the use of various treatment options has expanded, an overall assessment is required. OBJECTIVES: The following were compared to determine which resulted in improved patient-reported function, pain, and reoperation rates for each: (1) double-row (DR) fixation and single-row (SR) fixation in arthroscopic cuff repair; (2) latissimus dorsi transfer (LDT) with lower trapezius transfer (LTT), partial rotator cuff repair, and superior capsular reconstruction (SCR); and (3) early and late surgical intervention. METHODS: Medline, Embase, and Cochrane were searched through to April 20, 2021. Additional studies were identified from reviews. The following were included: (1) All English-language randomized controlled trials (RCTs) in patients ≥18 years of age comparing SR and DR fixation, (2) observational studies comparing LDT with LTT, partial repair, and SCR, and (3) observational studies comparing early vs. late treatment of full-thickness rotator cuff tears. RESULTS: A total of 15 RCTs (n = 1096 randomized patients) were included in the meta-analysis of SR vs. DR fixation. No significant standardized mean differences in function (0.08, 95% confidence interval [CI] -0.09, 0.24) or pain (-0.01, 95% CI -0.52, 0.49) were observed. There was a difference in retear rates in favor of DR compared with SR fixation (RR 1.56, 95% CI 1.06, 2.29). Four studies were included in the systematic review of LDT compared with a surgical control. LDT and partial repair did not reveal any differences in function (-1.12, 95% CI -4.02, 1.78) on comparison. A single study compared arthroscopically assisted LDT to LTT and observed a nonstatistical difference in the Constant score of 14.7 (95% CI -4.06, 33.46). A single RCT compared LDT with SCR and revealed a trend toward superiority for the Constant score with SCR with a mean difference of -9.6 (95% CI -19.82, 0.62). Comparison of early vs. late treatment revealed a paucity of comparative studies with varying definitions of "early" and "late" treatment, which made meaningful interpretation of the results difficult. CONCLUSION: DR fixation leads to similar improvement in function and pain compared with SR fixation and results in a higher healing rate. LDT transfer yields results similar to those from partial repair, LTT, and SCR in functional outcomes. Further study is required to determine the optimal timing of treatment and to increase confidence in these findings. Future trials of high methodologic quality comparing LDT with LTT and SCR are required.

Patients with stable coronary artery disease and type 2 diabetes but without prior myocardial infarction or stroke and THEMIS-like patients: real-world prevalence and risk of major outcomes from the SNDS French nationwide claims database.

AIM AND HYPOTHESES: The THEMIS randomized trial compared ticagrelor plus aspirin versus placebo plus aspirin for patients with stable coronary artery disease and type 2 diabetes mellitus (CAD-T2DM), and without prior myocardial infarction (MI) or stroke. The aim of the study was to quantify the size of the CAD-T2DM population without prior MI or stroke population in a real-world setting, and more specifically populations with similar THEMIS selection criteria (THEMIS-like and THEMIS-PCI-like populations), as well as their risk of major outcomes in current practice. METHODS: A 2-year follow-up cohort study included all CAD-T2DM without MI/stroke prevalent patients on January 1st, 2014 in the SNDS French nationwide claims database. The THEMIS-like population concerned those ≥ 50 years of age with similar THEMIS inclusion and exclusion criteria. Prevalence was standardized to the European population. The cumulative incidence function was used to estimate the incidence of clinical outcomes (MI, ischemic stroke, and major bleeding according to the TIMI classification) with death as competing risk, and the Kaplan-Meier estimate for all-cause death and a composite outcome of MI, stroke and all-cause death. RESULTS: From a population of about 50 million adults, the prevalence of CAD-T2DM without MI/stroke, THEMIS-like and THEMIS-PCI-like populations was respectively at 6.04, 1.50 and 0.27 per 1000 adults, with a mean age of 72.7, 72.3 and 70.9 years and less comorbidities and diabetic complications for the THEMIS-like and THEMIS-PCI-like population. The 2-year cumulative incidence was respectively 1.7%, 1.3% and 1.6% for MI, 1.7%, 1.5% and 1.4% for stroke, 4.8%, 3.1% and 2.9% for major bleeding, 13.6%, 9.7% and 6.8% for all-cause death, and 16.2%, 12.0% and 9.5% for the composite outcome. CONCLUSION: THEMIS-like prevalence was estimated at 1.50 per 1,000 adults, representing about a quarter of CAD-T2DM without MI/stroke patients, and 0.27 per 1000 adults for the THEMIS-PCI-like populations. In current French practice, the median age of both these populations was about 5-6 years older than in the THEMIS trial, with a 2-year incidence of major outcomes between two or four time above the ones of the placebo arm of the THEMIS trial using very close definitions. Registration No. EUPAS27402 ( http://www.ENCEPP.eu ).

Characterization of non-response to cardiac resynchronization therapy by post-procedural computed tomography.

INTRODUCTION: Causes of non-response to cardiac resynchronization therapy (CRT) include mechanical dyssynchrony, myocardial scar, and suboptimal left ventricular (LV) lead location. We aimed to assess the utility of Late Iodine Enhancement Computed Tomography (LIE-CT) with image subtraction in characterizing CRT non-response. METHODS: CRT response was defined as a decrease in LV end-systolic volume > 15% at 6 months. LIE-CT was performed after 6 months, and analyzed global and segmental dyssynchrony, myocardial scar, coronary venous anatomy, and position of LV lead relative to scar and segment of latest mechanical contraction. RESULTS: We evaluated 29 patients (age 71 ± 12 years; 72% men) including 18 (62%) responders. All metrics evaluating residual dyssynchrony such as wall motion index and wall thickness index were worse in non-responders. There was no difference in presence and extent of scar between responders and non-responders. However, in non-responders, the LV lead was more often over an akinetic/dyskinetic area (72% vs. 22%, p = .007), a fibrotic area (64% vs. 8%, p = .0007), an area with myocardial thickness < 6 mm (82% vs. 22%, p = .002), and less often concordant with the region of maximal wall thickness (9% vs. 72%, p = .001). Among the 11 non-responders, eight had at least another coronary venous branch visualized by CT, including three (27%) coursing over a potentially interesting myocardial area (free of scar, with normal wall motion, and with a myocardial thickness ≥6 mm). CONCLUSION: LIE-CT with image subtraction allows a comprehensive characterization of patients after CRT and may provide clues for management of non-responders.

Prion-like proteins as epigenetic devices of stress adaptation.

Epigenetic modifications allow cells to quickly alter their gene expression and adapt to different stresses. In addition to direct chromatin modifications, prion-like proteins have recently emerged as a system that can sense and adapt the cellular response to stressful conditions. Interestingly, such responses are maintained through prions' self-templating conformations and transmitted to the progeny of the cell that established a prion trait. Alternatively, mnemons are prion-like proteins which conformational switch encodes memories of past events and yet does not propagate to daughter cells. In this review, we explore the biology of the recently described prions found in Saccharomyces cerevisiae including [ESI+], [SMAUG+], [GAR+], [MOT3+], [MOD+], [LSB+] as well as the Whi3 mnemon. The reversibility of the phenotypes they encode allows cells to remove traits which are no longer adaptive under stress relief and chaperones play a fundamental role in all steps of prion-like proteins functions. Thus, the interplay between chaperones and prion-like proteins provides a framework to establish responses to challenging environments.

Comparison of the Analgesic Duration of 0.5% Bupivacaine With 1:200,000 Epinephrine Versus 0.5% Ropivacaine Versus 1% Ropivacaine for Low-Volume Ultrasound-Guided Interscalene Brachial Plexus Block: A Randomized Controlled Trial.

BACKGROUND: Bupivacaine and ropivacaine are the preferred long-acting local anesthetics for peripheral nerve blocks as they provide prolonged analgesia in the postoperative period. No studies have directly compared the analgesic duration of these commonly used local anesthetics in the setting of low-volume ultrasound-guided interscalene block (US-ISB). This study was designed to determine which local anesthetic and concentration provides superior analgesia (duration and quality) for low-volume US-ISB. METHODS: Sixty eligible patients scheduled for arthroscopic shoulder surgery were randomized (1:1:1) to receive US-ISB (5 mL) with 0.5% bupivacaine with 1:200,000 epinephrine, 0.5% ropivacaine, or 1% ropivacaine. All individuals were blinded including study participants, anesthesiologists, surgeons, research personnel, and statistician. All participants received a standardized general anesthetic and multimodal analgesia. The primary outcome was duration of analgesia defined as the time from the end of injection to the time that the patients reported a significant increase in pain (>3 numeric rating scale [NRS]) at the surgical site. RESULTS: The mean duration of analgesia for 0.5% bupivacaine with 1:200,000 epinephrine, 0.5% ropivacaine, or 1% ropivacaine was 14.1 ± 7.4, 13.8 ± 4.5, and 15.8 ± 6.3 hours, respectively (analysis of variance [ANOVA], P = .51). There were no observed differences in analgesic duration or other secondary outcomes between the 3 groups with the exception of a difference in cumulative opioid consumption up to 20h00 on the day of surgery in favor of ropivacaine 0.5% over bupivacaine of minimal clinical significance. CONCLUSIONS: In the context of single-injection low-volume US-ISB, we have demonstrated a similar efficacy between equal concentrations of ropivacaine and bupivacaine. In addition, increasing the concentration of ropivacaine from 0.5% to 1% did not prolong the duration of US-ISB.

Primary arthroscopic repair of massive rotator cuff tears results in significant improvements with low rate of re-tear.

PURPOSE: To conduct a systematic review of outcomes following primary arthroscopic repair of chronic massive rotator cuff tears (RCTs) and to assess clinical outcomes and rates of repair failure. The authors' preferred treatment algorithm is also provided. METHODS: Medline, Embase and PubMed were searched identifying articles pertaining to primary arthroscopic repair of chronic massive RCTs without the use of augmentation. Primary outcomes were patient-reported outcomes and the secondary outcome was the rate of repair failure. Outcome data were pooled and presented as well as assessment of study methodological quality. Data from studies reporting similar outcome measures were pooled when possible, and mean differences alongside confidence intervals and p values were reported, where appropriate. RESULTS: Twenty-six studies (1405 participants) were included, with mean age of 62 years (range 52-69). The mean duration of symptoms pre-operatively was 31 months (range 6-40), and the mean follow-up time was 39 months (range 12-111). Complete repair was performed in 78% of patients and partial repair was performed in 22%. Both complete and partial repairs resulted in significant improvements with respect to pain, range of motion and functional outcome scores. The rate of repair failure for the total cohort was 36% at a mean follow-up of 31 months, and for the complete and partial repair subgroups the failure rate was 35% and 40%, respectively. CONCLUSIONS: Arthroscopic repairs of chronic, massive RCTs, whether complete or partial, are associated with significant improvements in pain, function and objective outcome scores. The rate of repair failure is lower than previously reported, however, still high at 36%. The present paper finds that arthroscopic repair is still a viable treatment option for massive RCTs. LEVEL OF EVIDENCE: IV.

Risk of Total Hip Arthroplasty After Acetabular Fracture Fixation: The Importance of Age.

BACKGROUND: Geriatric patients are the most rapidly growing cohort of patients sustaining acetabular fractures (AFs). The purpose of this study was to examine the risk of a secondary total hip arthroplasty (THA) in older patients (>60 year old) with a prior AF open reduction internal fixation (ORIF) compared with younger patients (<60 year old) with an AF ORIF on a large population level. METHODS: Using administrative health care data from 1996 to 2010 inclusive of all 202 hospitals in Ontario, Canada, all adult patients with an AF ORIF and a minimum of two year follow-up were identified and included. The risk of THA was examined using a Cox proportional hazards model adjusting for patient risk factors. Secondary outcomes included surgical complications and all-cause mortality. RESULTS: A total of 1725 patients had an AF ORIF; 1452 (84.2%, mean age of 38.3 ± 12.1 years) aged <60 years ("younger") and 273 (15.8%, mean age of 69.9 ± 7.8 years) > 60 years ("older"). The mean (SD) follow-up time for all patients was 6.9 (4.2) years. In older patients, 19.4% (53 of 273) went on to receive a secondary THA with a median time to event of 3.9 years, compared with 12.9% (187 of 1452) in the younger patient cohort with a median time of 6.9 years (HR 1.7, 95% CI: 1.2-2.3). As expected, older patients had a higher 90-day mortality rate compared with younger patients (7.7% vs. 0.7%, respectively; HR 9.2, 95% CI: 4.3-19.9; P < .001). CONCLUSION: Older patients with an AF ORIF are at a significantly higher risk for a secondary THA than younger patients with an AF ORIF.