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Rationale: The proportion of patients who develop progressive pulmonary fibrosis (PPF), along with risk factors for progression remain poorly understood., Objectives: To examine factors associated with an increased risk of developing PPF among patients at a referral center., Methods: We identified patients with a diagnosis of interstitial lung disease (ILD) seen within the Cleveland Clinic Health System. Utilizing a retrospective observational approach we estimated the risk of developing progression by diagnosis group and identified key clinical predictors using the FVC component of both the original progressive fibrotic interstitial lung disease (PFILD) and the proposed PPF (ATS) criteria., Results: We identified 5934 patients with a diagnosis of ILD. The cumulative incidence of progression over the 24 months was similar when assessed with the PFILD and PPF criteria (33.1 % and 37.9 % respectively). Of those who met the ATS criteria, 9.5 % did not meet the PFILD criteria. Conversely, 4.3 % of patients who met PFILD thresholds did not achieve the 5 % absolute FVC decline criteria. Significant differences in the rate of progression were seen based on underlying diagnosis. Steroid therapy (HR 1.46, CI 1.31-1.62) was associated with an increased risk of progressive fibrosis by both PFILD and PPF criteria., Conclusion: Regardless of the definition used, the cumulative incidence of progressive disease is high in patients with ILD in the 24 months following diagnosis. Some differences are seen in the risk of progression when assessed by PFILD and PPF criteria. Further work is needed to identify modifiable risk factors for the development of progressive fibrosis., Competing Interests: Declaration of competing interest The study is funded by Boehringer Ingelheim Pharmaceuticals, Inc (BIPI). The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). Maeve Macmurdo, Xinge Ji, Alex Milinovich, Blaine Martyn-Dow, Aman Pande, Alex Zajichek, Janine Bauman, David Sugano, Michael W. Kattan and Daniel A. Culver are employed by the Cleveland Clinic which received research support from BIPI to collaborate on this project. Pratik Pimple, Amy L. Olson, Shaun Bender, and Craig Conoscenti are employees of BIPI. Daniel Culver received honoraria from BIPI for his participation in a Steering Committee, from Pliant for his participation in an Adjudication Committee and coverage for travel costs from Roche. All other members of the Cleveland Clinic study team cited no other disclosures., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The current standard of stethoscope hygiene doesn't eliminate the transmission of harmful pathogens, including multi-drug resistant organisms (MDROs). In the era of the increasing prevalence of MDRO infections, the use of new systems providing touch free barriers may improve patient safety versus traditional stethoscope cleaning practices with chemical agents. Our purpose was to provide a narrative literature review regarding barriers as an improvement over the current standard of care for stethoscope hygiene. Searching PubMed, articles were identified if they were in English and published after 1990, using the search term "stethoscope barrier", or if they were from a previously published stethoscope hygiene article using "author's name + stethoscope". Included articles evaluated or discussed stethoscope barriers. Of 28 manuscripts identified, 15 met the inclusion criteria. Barriers were considered superior to alternatives if they were single use, disposable, applied in a touch free fashion, were impervious to pathogens, provided an aseptic patient contact, and were acoustically invisible. Use of a practitioner's personal stethoscope with a disposable diaphragm barrier should be recommended as a new standard of care as this represents an improvement in patient safety and patient experience when compared to the disposable stethoscope or isopropyl alcohol stethoscope diaphragm cleaning., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: W. Frank Peacock, MD, FACEP, FACC, FESC, has served as the chief medical officer, and the other authors have served as intermittent consultants for Aseptiscope., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction and Background: Recent medical advances, including closure of myelomeningocele defects, shunting of hydrocephalus, and focusing on renal preservation have led to many individuals with spina bifida (SB) living into adulthood. This has led to more individuals with SB transitioning their care from pediatric-based to adult-based care models., Objective: We seek to explore the process of transition, with a focus on difficulties in transitioning individuals with SB. Additionally, we explore new problems that arise during the period of transition related to sexual function and dysfunction. We also discuss some of the difficulties managing neurogenic bladder and the sequalae of their prior urologic surgeries., Study Design: Each of the authors was asked to provide a summary, based on current literature, to highlight the challenges faced in their area of expertise., Conclusions: Transitioning care for individuals with SB is especially challenging due to associated neurocognitive deficits and neuropsychological functioning issues. Sexual function is an important component of transition that must be addressed in young adults with SB. Management of neurogenic bladder in adults with SB can be challenging due to the heterogeneity of the population and the sequelae of their prior urologic surgeries. The aim is to ensure that all individuals with SB receive appropriate, evidence-based care throughout their lifetime., (Copyright © 2023 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Facial nerve function is essential for a multitude of processes in the face, including facial movement; expression; and functions, such as eating, smiling, and blinking. When facial nerve function is disrupted, facial paralysis may occur and various complications for the patient may result. Much research has been conducted on the physical diagnosis, management, and treatment of facial paralysis. However, there is a lack of knowledge of the psychological and social effects of the condition. Patients may be at an increased risk for anxiety and depression, as well as negative self and social perceptions. This review analyzes the current literature on the various adverse psychological and psychosocial effects of facial paralysis, factors that may play a role, and treatment options that may help improve patients' quality of life., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: Compare transversus abdominis plane (TAP) blocks with liposomal bupivacaine were to epidural analgesia for pain at rest and opioid consumption in patients recovering from abdominal surgery., Background: ERAS pathways suggest TAP blocks in preference to epidural analgesia for abdominal surgery. However, the relative efficacies of TAP blocks and epidural analgesia remains unknown., Methods: Patients having major abdominal surgery were enrolled at six sites and randomly assigned 1:1 to thoracic epidural analgesia or bilateral/4-quadrant TAP blocks with liposomal bupivacaine. Intravenous opioids were used as needed. Non-inferiority margins were a priori set at 1 point on an 11-point pain numeric rating scale for pain at rest and at a 25% increase in postoperative opioid consumption., Results: Enrollment was stopped per protocol at 3rd interim analysis after crossing an a priori futility boundary. 498 patients were analyzed (255 had TAP blocks and 243 had epidurals). Pain scores at rest in patients assigned to TAP blocks were significantly non-inferior to those given epidurals, with an estimated difference of 0.09 points (CI: -0.12, 0.30; noninferiority P < 0.001). Opioid consumption during the initial 3 postoperative days in TAP patients was not non-inferior to epidurals, with an estimated ratio of geometric means of 1.37 (CI: 1.05, 1.79; non-inferiority P = 0.754). However, the absolute difference was only 21 mg morphine equivalents over the 3 days. Patients with epidurals were more likely to experience mean arterial pressures <65 mmHg than those given TAP blocks: 48% versus 31%, P = 0.006., Conclusion: Pain scores at rest during the initial three days after major abdominal surgery were similar. Patients assigned to TAP blocks required more opioid then epidural patients but had less hypotension. Clinicians should reconsider epidural analgesia in patients at risk from hypotension., Trial Registration: ClinicalTrials.gov Identifier: NCT02996227., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Stimulator of interferon genes (STING) plays an important role in infection, autoimmune disease and cancer. STING-mediated type I interferon (IFN) signaling is well recognized and extensively studied. Several IFN-independent activities of STING were also discovered in recent years and their physiological importance has begun to be appreciated. Here, we review recent advance in the evolutionary origin and molecular mechanisms of STING-mediated IFN-independent activities. New insights from these studies suggest that STING is not just a simple IFN-producing machine, rather, it functions as a hub that converts multiple environmental cues into diverse cellular responses . This expanded view of STING biology should guide future clinical testing of STING agonists in cancer and treatment of STING-associated human diseases., Competing Interests: Declaration of Competing Interests The authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: We did a comparative analysis of matched and mismatched defects in pre- and post-operative V/Q scans in CTEPH patients. We correlated the number of these defects with pre-operative clinical and hemodynamic parameters., Methods: This was a retrospective study on 27 patients with CTEPH who underwent surgery. Pre- and post-operative V/Q scans were graded for each lung segment as normal, matched or mismatched defect. Additional pre- and post-operative clinical and hemodynamic parameters that were collected include New York Heart Association functional class, six-minute walk distance in feet, N-terminal pro b-type natriuretic peptide, forced expiratory volume in one second/forced vital capacity, diffusing capacity of the lung for carbon monoxide, pulmonary arterial pressure (systolic, diastolic and mean), right atrial pressure, cardiac output and cardiac index. Pulmonary vascular resistance was then calculated., Results: On a segmental basis, 176 mismatched defects were noted in 27 patients, of which 111 improved post-surgery (63%). 22 of the 34 matched defects improved following surgery (64%). 31 new mismatched defects were observed. The number of pre-operative matched defects per patient ranged from 0 to 6. No statistically significant associations were observed between the number of pre-operative matched defects and pre-operative clinical parameters. No statistically significant associations were observed between the number of improved matched defects and the change in clinical parameters (pre- to post-surgery)., Conclusion: Both matched and mismatched defects on preoperative V/Q scans can show normalization post-surgery. The extent of matched defects on a preoperative V/Q scan does not correlate significantly with other clinical and hemodynamic parameters., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To determine if the Argus II retinal prosthesis can operate during functional MRI (fMRI) and diffusion tensor imaging (DTI) acquisitions and if currents induced in the prosthesis by imaging are at safe levels., Materials and Methods: One Argus II retinal prosthesis was modified to enable current measurements during imaging. Active electronics were modified to enable operation during scans. Induced current was measured during diagnostic scans, which were previously shown to be safe for implanted patients, and during fMRI and DTI scans. All measurements were performed using an ASTM phantom to ensure reproducible placement., Results: The prosthesis was able to maintain communication with the external RF coil during the fMRI and DTI scans except briefly during pre-scans. Current levels induced during fMRI and DTI scans were consistently below those measured during diagnostic scans., Conclusions: fMRI and DTI may be safely performed while the Argus II retinal prosthesis is operating., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Psychological symptoms are frequently reported in patients with Postural Orthostatic Tachycardia Syndrome (POTS); however, the nature of these symptoms is not well understood. The current study described baseline psychological symptoms in patients with POTS, and examined associations between psychological and self-report autonomic symptoms. Participants reported mild anxiety symptoms, moderate depressive symptoms, severe somatization, and elevated anxiety sensitivity. Depressive symptoms and pain catastrophizing were significantly associated with autonomic symptoms. The current study adds to the literature by documenting elevated levels of anxiety sensitivity, and relationships between psychological and autonomic symptoms., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: POTS patients undergo labial salivary gland biopsies (LSGB) for histologic confirmation of Sjogren's syndrome (SS). Predictive features of positive results are unknown., Methods: 161 POTS patients underwent LSGB. Their charts were reviewed for antibody and diagnostic testing results., Results: Only 11% (17/161) of POTS patients were SS positive. There were more positive ANA antibodies in those with positive LSGB (65% v 28%, p = .0026). Positive skin nerve biopsy for small fiber neuropathy (SFN) was associated with positive LSGB (p = .046)., Conclusion: A positive ANA and skin biopsy for SFN are two helpful features in selecting POTS patients for LSGB., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Artificial intelligence, and more narrowly machine-learning, is beginning to expand humanity's capacity to analyze increasingly large and complex datasets. Advances in computer hardware and software have led to breakthroughs in multiple sectors of our society, including a burgeoning role in medical research and clinical practice. As the volume of medical data grows at an apparently exponential rate, particularly since the human genome project laid the foundation for modern genetic inquiry, informatics tools like machine learning are becoming crucial in analyzing these data to provide meaningful tools for diagnostic, prognostic, and therapeutic purposes. Within medicine, hematologic diseases can be particularly challenging to understand and treat given the increasingly complex and intercalated genetic, epigenetic, immunologic, and regulatory pathways that must be understood to optimize patient outcomes. In acute myeloid leukemia (AML), new developments in machine learning algorithms have enabled a deeper understanding of disease biology and the development of better prognostic and predictive tools. Ongoing work in the field brings these developments incrementally closer to clinical implementation., (Copyright © 2020. Published by Elsevier Ltd.)

The treatment of locally advanced oral cavity cancer is often multimodal, involving surgical resection, radiotherapy (RT), and chemotherapy. Systemic therapy is the mainstay of treatment for recurrent/metastatic disease. While the concurrent use of cisplatin with post-operative RT is well established in patients with high risk features of extranodal extension and/or positive surgical margins following resection, the role of chemotherapy in other curative settings is not clear. Studies reporting success of induction chemotherapy or definitive chemoradiotherapy in absence of primary resection include all anatomic sites of head and neck cancer, and oral cavity cancer subset is rarely reported as a separate analysis, thus limiting the interpretation of results. This article will focus on the use of systemic therapy for locoregionally advanced oral cavity cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

•This case reports the treatment of neuroendocrine carcinoma of the cervix with a PARPi based on NGS.•NGS reports have demonstrated somatic mutations BRCA in neuroendocrine carcinoma of the cervix.•The use of a PARPi in neuroendocrine carcinoma of the cervix has not been previously reported., Competing Interests: None., (© 2019 Published by Elsevier Inc.)

Fluorescence and autofluorescence have been shown by several recent studies to be valuable adjuncts in identifying parathyroid glands during thyroidectomy and parathyroidectomy. The aim of this chapter is to review the impact of this new technology on surgical strategy concerning identification and preservation of parathyroid glands during thyroidectomy, identification of parathyroid glands in hyperparathyroidism, and the potential role in thyroid cancer surgery., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: We propose a Phase III trial that compares the effectiveness of an exercise training program delivered in a facility-based setting with direct, in-person supervision or a home-based setting with remote supervision via telerehabilitation for improving walking performance in persons with multiple sclerosis(MS) who have walking dysfunction and mobility disability., Methods/design: The study was developed with stakeholder engagement and is a multi-site trial that follows a 2-stage, randomized choice design. The trial compares the effectiveness of a 16-week evidence-based, individualized exercise program delivered in a supervised, facility-based setting versus a remotely coached/guided, home-based setting using telerehabilitation in physically inactive and cognitively intact people with MS who have walking dysfunction and mobility disability(N = 500). The primary outcome is walking speed. The secondary outcomes are walking endurance, disability status, and patient-reported outcomes of physical activity, walking impairment, fatigue, and quality of life. The components of the exercise program itself are similar between the groups and follow the Guidelines for Exercise in MS protocol. This includes a program manual, exercise prescription, exercise equipment, social-cognitive theory materials including newsletters, logs, and calendars, and one-on-one behavioral coaching by exercise specialists with background in MS. The main difference between groups is the coaching approach and setting for delivering the exercise training program. The outcomes will be collected by treatment-blinded assessors at baseline(week 0), mid-intervention(week 8), post-intervention(week 16), and follow-up(week 52)., Discussion: The proposed study will provide evidence for the effectiveness of a novel, widely-scalable program for delivering exercise training in persons with MS who have walking dysfunction and mobility disability., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Major depressive disorder (MDD) is the most common mental illness and the leading cause of disability worldwide. Electroconvulsive therapy (ECT) is the most effective treatment for MDD and the gold-standard therapy for treatment-resistant depression (TRD), yet it remains underutilized due to factors such as limited availability, stigma, and concerns about cognitive side effects. Ketamine has emerged as the first rapid-acting antidepressant and shows robust short-term efficacy in clinical trials, but there are concerns about its long-term safety and efficacy. While response rates are similar between ECT and ketamine in clinical trials, these treatments have never been compared head-to-head in a sufficiently large, well-powered randomized study. Here we describe the study protocol for ELEctroconvulsive therapy (ECT) vs. Ketamine in patients with Treatment-resistant Depression (ELEKT-D), a non-inferiority, comparative effectiveness trial. Patients with TRD seeking clinical treatment are randomized (1:1) to receive ECT (thrice weekly) or intravenous ketamine (twice weekly) for 3-5 weeks. The primary outcome is the proportion of responders in each group at the end of study visit, as measured by a patient-reported outcome measure (Quick Inventory of Depressive Symptomatology-Self Report). The study is powered such that the non-inferiority margin allows for ketamine to retain 90% of the ECT treatment effect, with a projected sample size of 400 patients (200 per group). Secondary outcomes include remission rates, depression severity, cognitive functioning, quality of life, adverse events, and tolerability. The results of the ELEKT-D study will have important implications for patient choice, clinical practice, and health insurance policies., (Copyright © 2018. Published by Elsevier Inc.)

Background and Aims: The optimal approaches to management of patients treated with moderate statin doses on lipid parameters are unknown. The ACCENTUATE study aimed to compare the effects of adding the cholesteryl ester transfer protein inhibitor (CETP) evacetrapib, ezetimibe or increasing statin dose in atorvastatin-treated high-vascular risk patients on lipid parameters., Methods: 366 patients with atherosclerotic cardiovascular disease (ASCVD) and/or diabetes were treated with atorvastatin 40 mg/day for 28 days prior to randomization to atorvastatin 40 mg plus evacetrapib 130 mg, atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe 10 mg or atorvastatin 40 mg plus placebo, daily for 90 days at 64 centers in the United States. Lipid parameters, safety and tolerability were measured., Results: Addition of evacetrapib significantly reduced LDL-C (-33%) compared with ezetimibe (-27%, p=0.045), increasing statin dose (-6%) and statin alone (0%, p<0.001). Evacetrapib also decreased apoB by 23% compared to 19% with ezetimibe (p=0.06) and 7% with increased statin dose (p<0.001), and reduced Lp(a) by 29% (p<0.001 vs. other groups). Evacetrapib increased HDL-C (+125%), apoA-I (+46%), apoC-III (+50%) and apoE (+28%) (p<0.001 vs. other groups). Non-ABCA1-mediated efflux increased by 53% (p<0.001 vs. other groups) with evacetrapib. ABCA1-mediated efflux also increased by 13% with evacetrapib (p<0.001 vs. ezetimibe, p=0.002 vs. increasing statin dose, and p=0.004 vs. statin alone). Addition of evacetrapib to atorvastatin produced an increase in hsCRP compared with ezetimibe (p=0.02)., Conclusions: While evacetrapib improved traditional atherogenic and putative protective lipid measures compared with ezetimibe and increasing statin dose in patients with ASCVD and/or diabetes, it also adversely affected novel atherogenic risk factors. These findings may contribute to the lack of clinical benefit observed in the ACCELERATE trial., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Multiple studies have sought to determine variables associated with improved "response" to cardiac resynchronization therapy(CRT). Such variables, however, are often derived from inadequately controlled, single center cohort studies calling external validity into question. We sought to determine predictors of response to CRT-D and CRT-P utilizing the methods of systematic review., Methods: We searched MEDLINE, Embase®, and the Cochrane Central Register of Controlled Trials (CENTRAL) from January 1, 1995, as this is the date of first article reporting use of CRT through October 20, 2014. Paired investigators independently screened search results to assess eligibility. For inclusion, investigators abstracted data sequentially and assessed risk of bias independently. Investigators graded the strength of evidence as a group., Results: We identified 13,015 unique citations of which 11,897 were excluded during the abstract screen. During the full-text screening, we excluded 1118 citations. 12 studies reported in 15 articles were included in this review. A left bundle branch (LBBB) morphology, non-ischemic cardiomyopathy (NICM), and female gender were generally associated with improved outcomes following CRT-D. Sinus rhythm (as compared to atrial fibrillation) and a wider QRS duration were associated with improved outcomes following CRT-D albeit with a lower strength of evidence. There was insufficient evidence to determine predictors of outcomes in patients undergoing CRT-P., Conclusions: A native LBBB, NICM, female gender, sinus rhythm, and a wider QRS duration are associated with improved outcomes following CRT-D implant., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Sarcopenia or loss of skeletal muscle mass is the major component of malnutrition and is a frequent complication in cirrhosis that adversely affects clinical outcomes. These include survival, quality of life, development of other complications and post liver transplantation survival. Radiological image analysis is currently utilized to diagnose sarcopenia in cirrhosis. Nutrient supplementation and physical activity are used to counter sarcopenia but have not been consistently effective because the underlying molecular and metabolic abnormalities persist or are not influenced by these treatments. Even though alterations in food intake, hypermetabolism, alterations in amino acid profiles, endotoxemia, accelerated starvation and decreased mobility may all contribute to sarcopenia in cirrhosis, hyperammonemia has recently gained attention as a possible mediator of the liver-muscle axis. Increased muscle ammonia causes: cataplerosis of α-ketoglutarate, increased transport of leucine in exchange for glutamine, impaired signaling by leucine, increased expression of myostatin (a transforming growth factor beta superfamily member) and an increased phosphorylation of eukaryotic initiation factor 2α. In addition, mitochondrial dysfunction, increased reactive oxygen species that decrease protein synthesis and increased autophagy mediated proteolysis, also play a role. These molecular and metabolic alterations may contribute to the anabolic resistance and inadequate response to nutrient supplementation in cirrhosis. Central and skeletal muscle fatigue contributes to impaired exercise capacity and responses. Use of proteins with low ammoniagenic potential, leucine enriched amino acid supplementation, long-term ammonia lowering strategies and a combination of resistance and endurance exercise to increase muscle mass and function may target the molecular abnormalities in the muscle. Strategies targeting endotoxemia and the gut microbiome need further evaluation., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: The aim was to report on chimney and periscope grafts (CPGs) and their mid- and longer-term outcomes when they are used to preserve reno-visceral artery (RVA) perfusion in endovascular repair of pararenal (PRAAs) or thoraco-abdominal aortic aneurysm (TAAAs). In addition, factors associated with CPG failure are presented. Limited data exist on the outcomes of CPGs, and mid- and long-term results are generally not reported., Methods: This was a prospective study in a cohort of 100 patients with PRAA (69) or TAAA (31). A total of 224 (mean 2.24 per patient) RVAs were preserved with 136 (61%) chimney and 88 (39%) periscope grafts. CPGs were constructed mainly using self expandable stent grafts. Patients were followed by clinical examination, CTA (82%), and/or duplex (18%). Data were collected until February 2015., Results: CPG immediate technical success was 99% (222/224 branches). Mean follow up was 29 months (range 0-65; SD 17); 59% patients were followed > 2 years, 30% > 3 years, and 16% > 4 years. Post-operatively, CPG occlusion was observed early (≤30 days) in three (1.3%) branches and during follow up in 10 (4.5%). At 36 and 48 months, the estimated primary patency was 93% and 93%. After corrective percutaneous (10) or surgical (3) re-interventions, the estimated secondary patency was 96% and 96%. Thirty day mortality was 2%; at 36 and 48 months the estimated patient survival was 79%. Significant shrinkage (72 [SD 23] vs. 62 [SD 24] mm; p < .001) was observed, with a substantial reduction (>5 mm) in 55 patients, and sac enlargement in four. Incomplete aneurysm sac sealing was treated successfully by a secondary intervention in 15 patients., Conclusions: Self expandable CPGs have proved to be a highly successful and durable treatment for RVA preservation up to 5 years. Incomplete CPG expansion, inadequate length, and CPG use in small and diseased target arteries were risk factors for occlusion. These mid- and longer-term results support CPG use to treat PRAAs or TAAAs in patients unfit for open surgery or fenestrated/branched stent grafts., (Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Balloon-expandable valves (BEVs) and self-expandable valves (SEVs) are two major types of valves utilized for transcatheter aortic valve replacement (TAVR). We conducted a meta-analysis of available studies to compare the safety and efficacy of these two valve types., Methods: Medline search was conducted using standard search terms to determine eligible studies. Primary outcomes of the meta-analysis included death and stroke at 30days and 1year. Pooled estimates of procedural outcomes were also compared between the valve types. Analysis was performed for entire cohort and separately for patients undergoing transfemoral TAVR (TF-TAVR)., Results: Analysis of entire cohort revealed similar 30-day mortality in the SEV and BEV cohorts. There was no significant difference in the incidence of stroke at 30days between the two study groups. Both pooled comparisons demonstrated a significant heterogeneity with I(2)>50%, necessitating the use of random effect modeling. We observed a significantly higher incidence of new pacemaker implantation, aortic regurgitation≥2+ at 30days, valve embolization, and need for >1 valve following SEV implantation compared with BEV implantation. Analysis of TF-TAVR cohort showed higher 30day [IRR (95% CI): 1.34 (1.19-1.52)] but a similar 1-year mortality [IRR (95% CI): 1.07 (0.96-1.19)] for SEV compared to BEV implantation., Conclusion: Compared to BEV implantation, SEV implantation was associated with a similar risk of mortality and stroke at 30-day and 1-year follow-up duration. Analysis of the TF-TAVR cohort revealed a significantly higher mortality at 30days among patients undergoing SEV implantation, compared with BEV implantation. In addition, there was a significantly higher incidence of other adverse events noted above, following SEV implantation, compared with BEV implantation., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

T cell depletion is an important procedure for both experimental and therapeutic immune modulation. Rabbit anti-thymocyte globulin (ATG), which is a commonly used T cell depletion antibody in clinical organ and cell transplantation protocols, is effective in temporarily depleting peripheral blood T lymphocytes but only moderately effective in depleting peripheral lymph node T cells which comprise the majority of T lymphocytes. A recombinant anti-CD3 immunotoxin, A-dmDT390-scfbDb (C207), has been developed and shown in an initial study to retain the lymph node depleting properties of conjugated CD3 immunotoxin. This agent could potentially be used synergistically with or as a replacement for rabbit ATG in preclinical primate models of transplantation. We directly compared the peripheral blood and lymph node depleting abilities of this recombinant anti-CD3 immunotoxin and rabbit ATG in naïve animals at clinically tolerated doses. Baboons were treated with a full course of either rabbit ATG (n=2) or CD3 immunotoxin (n=3). Peripheral blood and lymph node T lymphocytes were measured before and following treatment. Peripheral blood CD3+ cells fell below 100cells/μL in every animal. In the two animals receiving ATG, CD3+ cells represented 53% and 68% of lymph node cells two days following a full course of rabbit ATG. In contrast, CD3+ cells represented 3%, 5%, and 38% in lymph nodes following a full course of CD3-IT. Thus, recombinant anti-monkey CD3 immunotoxin showed improved peripheral lymph node T lymphocyte depletion to rabbit ATG and spared other immune cells., (© 2013.)

Background: TAVR has emerged as an attractive alternative for treatment of severe aortic stenosis in high risk surgical patients. Despite several large multicenter registries, only one randomized trial (PARTNER) has been published., Objective: We aimed to compare the outcomes obtained using multicenter registries and the PARTNER trial., Methods: Standard MEDLINE search strategy was used to find multicenter registries, reporting clinical outcomes following TAVR. Meta-analytic techniques were utilized to calculate pooled outcomes across multicenter registries and compare them to outcomes in PARTNER trial., Results: Pooled 30-day mortality rate from the registries was 9.2%, which was significantly higher than that in the PARTNER trial (3.8%). Medium-term mortality rates were similar between the PARTNER trial and the multicenter registries. Pooled 30-day and 1-year stroke rates in multicenter registries were 2.6% and 3.8%, respectively. On the other hand, the corresponding rates in PARTNER trial were 5.2% and 7.6%, respectively. In the registry-related cohorts, pooled 30-day and 1-year mortality rates were 6.8% and 20.8% in the transfemoral group and 12.2% and 32.2% in the transapical group. In the PARTNER trial, the pooled incidence of 30-day and 1-year mortality rates were 3.9% and 26.2% in the transfemoral group and 3.8% and 29.0% in the transapical group., Conclusions: Short-term results in PARTNER were better than those reported in the registries, which may be due to better patient selection and aggressive bailout techniques. Similarity of medium-term outcomes between registries and PARTNER highlights that patient selection for TAVR is critical due to considerable risk of mortality in the first year even after the successful procedure., (Copyright © 2013 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)