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OBJECTIVE: To examine the use of pharmacotherapy in obesity treatment in the United States from 2011 to 2016 using a large, nationally representative sample. PATIENTS AND METHODS: Data were obtained over six years, 2011 to 2016, from the National Ambulatory Medical Care Survey. There were three types of visits identified: patients with obesity and an anti-obesity drug mention, patients with obesity and no anti-obesity drug mention, and patients without obesity and with anti-obesity drug mention. Chi-square tests were used to compare characteristics across each type of visit. To predict the odds of an anti-obesity medication mention for patients with obesity, a logistic regression analysis was conducted. RESULTS: Of the overall weighted 196,872,870 office-based physician visits made by patients with obesity from 2011 to 2016, one percent mentioned an anti-obesity drug. Additionally, there were 760,470 office-based physician visits by patients without obesity but with an anti-obesity medication mention. An anti-obesity drug mention was more likely for those ages 51 or older and those residing in the South (AOR: 5.31 95% CI: 1.19-23.59). CONCLUSION: There was a slight increase in anti-obesity medication mentions, from 0.26% in 2011 to 0.28% in 2016, but only one percent of office-based visits for patients with obesity received a prescription for an anti-obesity medication. Physicians tended to prescribe anti-obesity medications to those with obesity ages 51 or older and residing in the South. Anti-obesity medication as treatment for obesity is significantly underutilized.

Myocardial bridge (MB) of the left anterior descending (LAD) coronary artery occurs in approximately 25% of the population. When medical therapy fails in patients with a symptomatic, hemodynamically significant MB, MB unroofing represents the optimal surgical management. Here, we evaluated minimally invasive MB unroofing in selected patients compared with sternotomy.MB unroofing was performed in 141 adult patients by sternotomy on-pump (ST-on, n = 40), sternotomy off-pump (ST-off, n = 62), or minithoracotomy off-pump (MT, n = 39). Angina symptoms were assessed preoperatively and 6 months postoperatively using the Seattle Angina Questionnaire. Matching included all MT patients and 31 ST-off patients with similar MB characteristics, no previous cardiac operations or coronary interventions, and no concomitant procedures.MT patients tended to have a shorter MB length than ST-on and ST-off patients (2.57 vs 2.93 vs 3.09 cm, P = .166). ST-on patients had a longer hospital stay than ST-off and MT patients (5.0 vs 4.0 vs 3.0 days, P .001), and more blood transfusions (15.2% vs 0.0% vs 2.6%, P = .002). After matching, MT patients had a shorter hospital stay than ST-off patients (3.0 vs 4.0 days, P = .005). No deaths or major complications occurred in any group. In all groups, MB unroofing yielded significant symptomatic improvement regarding physical limitation, angina stability, angina frequency, treatment satisfaction, and quality of life.We report our single-center experience of off-pump minimally invasive MB unroofing, which may be safely performed in carefully selected patients, yielding dramatic improvements in angina symptoms at 6 months after the operation.

Purpose: The purpose of this study is to evaluate the anatomical and functional outcomes of 25-gauge (G) pars plana vitrectomy (PPV) in patients with cytomegalovirus retinitis (CMVR)-related rhegmatogenous retinal detachment (RRD). Methods: Single-center retrospective consecutive case series of patients who underwent 25-G PPV for CMVR-related RRD repair with a minimum follow-up of 3 months. Complete anatomic success was defined as the complete attachment of retina including the periphery. Best-corrected visual acuity (BCVA) of ≥20/400 was defined as functional success. Results: Sixteen eyes of 15 patients were included in the study. Eleven patients were human immunodeficiency virus positive, three patients had hematological malignancies, and one patient suffered from dyskeratosis congenita. The mean follow-up was 20.5 ± 17.4 months (range 3–60 months). Complete anatomical success was seen in 15 eyes (93.75%). One eye had a residual inferior detachment with attached macula. Silicone oil was used as tamponade in 15 eyes and C3F8 gas in one eye. The mean change in BCVA was statistically significant, preoperative LogMAR BCVA was 2.05 ± 0.94 while the final follow-up postoperative LogMAR BCVA was 1.03 ± 0.61 (P < 0.001). Thirteen eyes (81.25%) had final BCVA ≥20/400. Conclusion: Microincision vitrectomy surgery can achieve excellent retinal reattachment rates in post-CMVR RRDs without significant intraoperative and postoperative complications. The visual outcome varies depending on the status of the optic disc and macula. Majority of the patients maintained functional vision.

OBJECTIVE The oscillations between binge eating, purging, and dieting in bulimia nervosa (BN) may produce substantial within-subject weight variability. Although weight variability has been predictive of eating- and weight-related variables in community samples, it has not been empirically examined in eating disorders. The current study examined cross-sectional and prospective associations between weight variability and BN pathology. METHOD Four weights were collected over an average of 42.02 days, and weight variability was calculated as the root mean square error around each individual's weight trajectory regression line. Linear regressions were performed to examine the association between weight variability and eating disorder psychopathology, cross-sectionally at baseline and prospectively at 6-month follow-up, adjusting for baseline BMI. RESULTS Weight variability was cross-sectionally associated with eating pathology, but these relationships became non-significant after adjusting for BMI. However, at 6-month follow-up, greater baseline weight variability predicted increases in body dissatisfaction, shape and weight concerns, and global eating pathology, even after adjusting for baseline BMI. DISCUSSION These findings demonstrate, for the first time, that within-subject weight variability predicts greater eating disorder pathology over time in BN. The results add to evidence that weight history variables contribute to BN psychopathology above and beyond well-documented psychological dysfunction in BN.

Purpose: The aim of this study was to evaluate the anatomic and functional outcomes of 25-gauge pars plana vitrectomy (25G PPV) with encircling scleral band (ESB) in patients with acute retinal necrosis (ARN)-related rhegmatogenous retinal detachment (RRD). Methods: Single-center retrospective interventional case series of patients who underwent 25G PPV with ESB for ARN-related RRD. Complete anatomic success was defined as the complete attachment of retina after primary PPV. Functional success was measured by the final best-corrected visual acuity (BCVA) ≥20/400. Intraoperative and postoperative complications were also noted. Results: 14 eyes of 13 patients were included in the study. Six patients (46.1%) were immunocompromised. The mean follow-up was 23.64 ± 9.95 (range 6-42) months. Silicone oil was used as tamponade in 13 eyes and C3F8gas in one eye. After the primary PPV, complete anatomical success was seen in all eyes (100%), however, one eye developed phthisis bulbi after silicone oil removal (SOR). Statistically significant improvement of BCVA was seen, from LogMAR 2.03 ± 0.29 preoperatively to LogMAR 1.57 ± 0.63 postoperatively (p-value 0.014). Six eyes (42.9%) had functional success. Nine eyes (64.3%) had improvement in vision while 4 eyes (28.6%) maintained preoperative vision. 10 eyes (71.4%) underwent cataract surgery, nine eyes (64.3%) underwent SOR while 2 eyes (14.3%) had epiretinal membrane (ERM) under oil during follow-up. Conclusion: 25G PPV combines the advantages of minimally invasive vitrectomy surgery while offering improved anatomic outcomes in patients with ARN-related RRD. The functional outcome varies depending on the status of the optic disc and macula.

PRECIS Ahmed glaucoma valve (AGV) implantation led to a significant reduction in intraocular pressure (IOP) and in antiglaucoma medications in vitrectomized eyes in previously nonglaucomatous eyes. The most common indication for vitrectomy was ocular trauma-related complications. PURPOSE The purpose of this study was to report the long-term outcomes of AGV implantation in patients of uncontrolled IOP after pars plana vitrectomy (PPV). MATERIALS AND METHODS Medical records of patients (age 18 y and above) who underwent AGV implantation between January 2006 and December 2017 for uncontrolled IOP following PPV with ≥2 years follow-up were reviewed. The underlying etiology for PPV, IOP, best-corrected visual acuity, and number of antiglaucoma medications (AGMs) were recorded at baseline. The main outcomes measures were IOP, number of AGM, best-corrected visual acuity, and postoperative complications. Postoperative complications were classified as early (≤3 mo)/intermediate (>3 mo to ≤1 y), or late (>1 y). RESULTS In all, 78 eyes of 78 patients with a mean age of 38.06±17.83 years were included. The mean follow-up was 70.46±36.96 (range: 24 to 180) months. The main underlying etiology for PPV was trauma (38.4%) followed by rhegmatogenous retinal detachment (28.2%). The mean preoperative IOP was 29.33±9.84 mm Hg with an average of 4.07±1.2 AGM. The mean IOP and number of AGM was significantly reduced in all follow-up visits (P

Objective Individuals with chronic pain conditions often report movement as exacerbating pain. An increasing number of researchers and clinicians have recognized the importance of measuring and distinguishing between movement-evoked pain (MEP) and pain at rest as an outcome. This scoping review maps the literature and describes MEP measurement techniques. Materials and methods The scoping review utilized 6 databases to identify original studies that targeted pain or movement-related outcomes. Our search returned 7322 articles that were screened by title and abstract by 2 reviewers. The inclusion criteria focused on the measurement of MEP before, during, and after movement tasks in adults with chronic pain. Studies of children below 18 years of age or with nonhuman animals, case studies, qualitative studies, book chapters, cancer-related pain, non-English language, and abstracts with no full publish text were excluded from the study. Results Results from 38 studies revealed great variation in the measurement of MEP, while almost all of the studies did not provide an explicit conceptual or operational definition for MEP. In addition, studies collectively illuminated differences in MEP compared with rest pain, movement provocation methods, and pain intensity as the primary outcome. Discussion These results have clinically significant and research implications. To advance the study of MEP, we offer that consistent terminology, standardized measurement (appropriate for pain type/population), and clear methodological processes be provided in research publications. On the basis of the findings, we have put forth a preliminary definition of MEP that may benefit from the continued scholarly dialog.

Purpose: Complex upper eyelid lacerations can present to the emergency department after a myriad of trauma. The goal of the surgical repair is anatomical and functional recovery along with symmetrical cosmesis. Despite meticulous surgery, post traumatic blepharoptosis may develop. We describe an additional step during upper eyelid laceration repair to help mitigate the development of traumatic blepharoptosis. Methods: Patients with traumatic eyelid laceration without head injury, globe injury or associated orbital fractures, who were planned for a primary upper eyelid repair were included. Intraoperatively, wound margins and tissues were identified to establish anatomical continuity. After the LPS muscle was reinserted onto the tarsus, a single, central suture LPS plication – the “ central levator tuck” was performed. This helped in improving the muscle action as well as strengthening its reattachment onto tarsus. Results: Four cases underwent laceration repair with this modified technique. The nature of eyelid injury, surgical technique, and the outcome at 6 months is described. Three patients had a successful outcome, whereas one patient developed early scarring which reduced with scar therapy over time. Conclusion: We describe a simple and effective “central levator tuck” technique for traumatic eyelid laceration repair with optimal functional and cosmetic outcome while reducing the development of blepharoptosis in four patients.

Background Eating disorders have serious psychological and physical consequences. Current evidence-based treatments for adolescents with eating disorders have modest effects, underscoring the need to improve current treatment approaches. Cognitive behavior therapy (CBT) and dialectical behavior therapy (DBT) have been proposed as alternative treatment options, with burgeoning research in this area. This review aims to summarize and critically analyze the current literature on the feasibility, acceptability, effectiveness, and efficacy of CBT and DBT for adolescent eating disorders, and then proposes areas of future research. Methods PsycINFO and PubMed were searched using the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to identify studies examining the feasibility, acceptability, effectiveness and/or efficacy of CBT or DBT for adolescent eating disorders. Results Eligible studies (N = 50; CBT: n = 40, DBT: n = 10) indicated that both treatments are reasonably feasible, acceptable, and possibly effective for adolescent eating disorders across diagnoses and levels of care, though efficacy trials are lacking. Conclusions CBT and DBT demonstrate promise as alternatives to family-based approaches for adolescent eating disorders. Adequately powered trials to establish the effectiveness and efficacy of CBT and DBT are needed, particularly ones that compare these treatments against other leading approaches. Plain English summary Despite high rates of relapse and likelihood for severe and enduring illness, there is a dearth of evidence-based treatment options for adolescents with eating disorders. Potentially viable but less well-studied treatments for adolescents with eating disorders include cognitive behavior therapy (CBT) and dialectical behavior therapy (DBT). This systematic review of CBT and DBT for adolescent eating disorders focuses on feasibility (i.e., how easy it was to implement the treatment), acceptability (i.e., how well the intervention was received by patients and therapists), effectiveness (i.e., how well the intervention performed under routine, real-world circumstances), and efficacy (i.e., how well the intervention performed in highly-controlled research settings). This review concludes that research supports the feasibility and acceptability of these approaches, as well as preliminary evidence of their effectiveness. However, the field is lacking studies that systematically compare CBT and DBT to other evidence-based approaches. Recommendations to advance research on CBT and DBT for adolescent eating disorders are provided, including a call for efficacy studies that clarify their performance compared to other leading approaches.

Pain is experienced by people with cancer during treatment and in survivorship. Exercise can have an acute hypoalgesic effect (exercise‐induced hypoalgesia; EIH) in healthy individuals and some chronic pain states. However, EIH, and the moderating effect of exercise intensity, has not been investigated in cancer survivors. This study examined the effect of low‐ and high‐intensity aerobic exercise on EIH in cancer survivors after a single exercise session as well as a brief period of exercise training (2‐weeks, three exercise sessions per week). Participants (N = 19) were randomized to low‐ (30%–40% Heart Rate Reserve (HRR) or high‐ (60%–70% HRR) intensity stationary cycling for 15–20 min. Pressure pain thresholds (PPT) were assessed over the rectus femoris and biceps brachii before and after a single exercise session and again after a short training period at the assigned intensity. Then, following a 6‐week washout period, the intervention was repeated at the other intensity. After the first exercise session, high‐intensity exercise resulted in greater EIH over the rectus femoris than low intensity (mean difference ± SE: −0.51 kg/cm2 ± 0.15, Cohen's d = 0.78, p = 0.004). After a 2‐week training period, we found no difference in EIH between intensities (0.01 kg/cm2 ± 0.25, d = 0.00 p = 0.99), with comparable moderate effect sizes for both low‐ and high‐intensity exercise, indicative of EIH. No EIH was observed over the biceps brachii of the arm at either low or high intensity. Low‐intensity exercise training may be a feasible option to increase pain thresholds in cancer survivors., High‐intensity exercise increased pressure pain thresholds more than low‐intensity exercise over the exercising muscle of the leg. However, after a short training period, there was no difference between low‐ and high‐intensity exercise on pain thresholds, with both intensities eliciting a hypoalgesic effect. These results suggest that both low‐ and high‐intensity exercise training may be effective at increasing pain thresholds in cancer survivors.

Bilateral diffuse uveal melanocytic proliferation (B-DUMP) is a paraneoplastic disorder that may be seen in patients with a known malignancy but more commonly is seen in those without any history of cancer. It leads to multiple uveal tumors with exudative retinal detachment along with thickening of the choroid and generally carries a poor prognosis. Its etio-pathogenesis is poorly understood but is said to involve factors secreted by the systemic malignancy that lead to proliferation of melanocytes in the uvea.We report the presentation and management of a female with history of treated frontal lobe meningioma who presented with neovascular glaucoma along with B-DUMP and was found to have recurrence of the meningioma on neuro-imaging.Central nervous system meningiomas can cause B-DUMP and management of the malignancy may lead to partial resolution of posterior segment manifestations of B-DUMP.

A 3-month-old girl presented with developmental delay and clustered asymmetric epileptic spasms (video). She was first-born to nonconsanguineous healthy parents with a smooth perinatal transition. Examination revealed normal head size, central hypotonia, and characteristic fundus findings (figure 1, A and B). EEG revealed hypsarrhythmia (figure 1C). Peculiar fundus and neuroimaging findings (figure 2) confirmed the diagnosis of Aicardi syndrome (AS). Epileptic spasms failed to respond to adrenocorticotropin and vigabatrin. This report emphasizes the utility of skillful neuroophthalmologic assessment in children with epileptic spasms.

The gastrointestinal mucosa is critical for maintaining the integrity and functions of the gut. Disruption of this barrier is a hallmark and a risk factor for many intestinal and chronic inflammatory diseases. Inflammatory bowel disease (IBD) and HIV infection are characterized by microbial translocation and systemic inflammation. Despite the clinical overlaps between HIV and IBD, significant differences exist such as the severity of gut damage and mechanisms of immune cell homeostasis. Studies have supported the role of metabolic activation of immune cells in promoting chronic inflammation in HIV and IBD. This inflammatory response persists in HIV+ persons even after long-term virologic suppression by antiretroviral therapy (ART). Here, we review gut dysfunction and microbiota changes during HIV infection and IBD, and discuss how this may induce metabolic reprogramming of monocytes, macrophages and T cells to impact disease outcomes. Drawing from parallels with IBD, we highlight how factors such as lipopolysaccharides, residual viral replication, and extracellular vesicles activate biochemical pathways that regulate immunometabolic processes essential for HIV persistence and non-AIDS metabolic comorbidities. This review highlights new mechanisms and support for the use of immunometabolic-based therapeutics towards HIV remission/cure, and treatment of metabolic diseases. Keywords: Inflammatory bowel disease, Inflammation, HIV cure, Macrophage metabolism, Immunometabolism, microbiome

Purpose: To study the role of ultra-wide field (UWF) fundus autofluorescence (FAF) in the management of CMV (cytomegalovirus) retinitis.Material and methods: In this prospective, observational, non-randomized study, we followed up patients with active CMV retinitis on UWF fundus photograph (FP) and UWF-FAF.Results: A total of 16 patients (24 eyes) were studied. There were 13 males and mean age of patients was 37 (range 9-56) years. On UWF FP, out of 24 eyes, 13 (54.2%) had granular lesions, 3 (12.5%) had necrotizing pattern, 1 (4.1%) had a frosted branch angiitis (FBA), and 7 (29.2%) had a mixed pattern. UWF-FAF showed better delineation of borders of lesions in 7 eyes (29.1%), larger area of involvement in 8 eyes (33.3%), picked up 7 of 9 (77.77%) eyes of recurrence and helped differentiate cotton wool spots from retinitis lesion in one eye.Conclusion: UWF-FAF is useful in the management of CMV retinitis.

Purpose Many women with eating disorders (EDs) have comorbid posttraumatic stress disorder (PTSD). However, there have been few studies on how comorbid PTSD may impact ED treatment outcomes. Method Participants were 2,809 patients from residential ED treatment facilities who were treated using the Unified Treatment Model (UTM). We investigated whether PTSD diagnosis at admission was associated with changes in Eating Disorder Examination-Questionnaire (EDE-Q) scores, binge eating, self-induced vomiting, and restriction, across three time points, as well as clinically significant improvement and treatment drop-out. Results Using latent growth models, with time modeled as a second-order polynomial, we found that EDE-Q scores and behavioral symptoms decreased from admission to discharge, but increased from discharge to 6-month follow-up. PTSD diagnosis was associated with higher baseline EDE-Q scores and restriction, and lower binge-eating frequency. PTSD diagnosis was not associated with symptom change over time, treatment dropout, or clinically significant change. Discussion Although PTSD diagnoses were associated with higher ED symptom levels at admission, PTSD was not associated with worse treatment outcomes, suggesting the UTM is a promising treatment for patients with and without PTSD. Future studies should investigate the impact of ED treatment on PTSD symptoms in order to determine the need for integrated treatments for these comorbid conditions.

Background:The Renfrew Unified Treatment for Eating Disorders and Comorbidity (UT) is a transdiagnostic, emotion-focused treatment adapted for use in residential group treatment. This study examined the effect of UT implementation across five years of treatment delivery.Methods:Data were collected by questionnaire at admission, discharge (DC), and 6-month follow-up (6MFU). Patient outcomes were measured by the Eating Disorder Examination-Questionnaire, Center for Epidemiologic Studies-Depression Scale, Brief Experiential Avoidance Questionnaire (BEAQ), Anxiety Sensitivity Index, and Southampton Mindfulness Scale. Data were analyzed forN= 345 patients treated with treatment-as-usual (TAU), andN= 2,763 treated with the UT in subsequent years.Results:Results from multilevel models demonstrated a significant interaction between implementation status (TAU vs. UT) and time, both linear and quadratic, for the depression, experiential avoidance, anxiety sensitivity, and mindfulness variables. Patients treated with the UT showed more improvement in these variables on average, as well as more rebound between DC and 6MFU. Results from multilevel models examining eating disorder outcome showed no significant difference between the TAU and UT for the full sample, but a significant three-way interaction indicated that the UT produced more improvement in the EDE-Q relative to the TAU particularly for patients who entered treatment with high levels of experiential avoidance (BEAQ score).Conclusion:This long-term study of a transdiagnostic, evidence-based treatment in residential care for eating disorders and comorbidity suggests implementation was associated with beneficial effects on depression and emotion function outcomes, as well as eating disorder severity for patients with high levels of baseline emotion regulation problems. These effects did not appear to diminish in the 5 years following initial implementation.

Background: We examined the effect of power training on habitual, intervention and total physical activity (PA) levels in older adults with type 2 diabetes and their relationship to metabolic control. Materials and Methods: 103 adults with type 2 diabetes were randomized to receive supervised power training or sham exercise three times/week for 12 months. Habitual, intervention, and total PA, as well as insulin resistance (HOMA2-IR) and glycosylated hemoglobin (HbA1c), were measured. Results: Participants were aged 67.9 ± 5.5 yrs, with well-controlled diabetes (HbA1c = 7.1%) and higher than average habitual PA levels compared to healthy peers. Habitual PA did not change significantly over 12 months (p = 0.74), and there was no effect of group assignment on change over time in habitual PA over 0–6 (p = 0.16) or 0–6–12 months (p = 0.51). By contrast, intervention PA, leg press tonnage and total PA increased over both 6- and 12-month timepoints (p = 0.0001), and these changes were significantly greater in the power training compared to the sham exercise group across timepoints (p = 0.0001). However, there were no associations between changes in any PA measures over time and changes in metabolic profile. Conclusion: Structured high-intensity power training may be an effective strategy to enhance overall PA in this high-risk cohort.

Risks to health are the prime consideration in all human situations of ionizing radiation exposure and therefore of relevance to radiation protection in all occupational, medical, and public exposure situations. Over the past few decades, advances in therapeutic strategies have led to significant improvements in cancer survival rates. However, a wide range of long-term complications have been reported in cancer survivors, in particular circulatory diseases and their major risk factors, metabolic diseases. However, at lower levels of exposure, the evidence is less clear. Under real-life exposure scenarios, including radiotherapy, radiation effects in the whole organism will be determined mainly by the response of normal tissues receiving relatively low doses, and will be mediated and moderated by systemic effects. Therefore, there is an urgent need for further research on the impact of low-dose radiation. In this article, we review radiation-associated risks of circulatory and metabolic diseases in clinical, occupational or environmental exposure situations, addressing epidemiological, biological, risk modelling, and systems biology aspects, highlight the gaps in knowledge and discuss future directions to address these gaps.

Introduction: There is growing concern regarding the attrition of surgeon-scientists in cardiothoracic (CT) surgery. The academic impact of conducting basic science research (BSR) during training, however, remains unknown. We hypothesized that CT surgeons who publish a first-author BSR paper during training exhibit enhanced future academic productivity. Methods: CT surgeons on faculty at accredited United States CT surgery training hospitals in 2018 who published a first-author BSR paper or a first-author clinical research (CR) paper during training were identified (n=762). To normalize for environmental differences in research exposure, we specifically studied the surgeons who pursued a research fellowship and who attended a top-50 NIH-funded institution at every stage of training (n=252). Data regarding each surgeon’s professional history and publication record were obtained from publicly-available online sources. Results: As shown in Table 1, surgeons who published a first-author paper in BSR during training and those who published a first-author paper only in CR share similar characteristics and have practiced as an attending surgeon for a similar duration (11.0 years each, p=0.486). However, surgeons who published a first-author BSR paper during training ultimately published more papers per year as an attending (4.3 vs 2.8, p=0.017), resulting in more total publications (73.5 vs 47.5, p=0.003) and a greater H-index (22.0 vs 18.0, p=0.004). The surgeons who published a first-author BSR paper during training were also more likely to have published a BSR paper in the past 2 years as an attending, both as a first or last author (12.0% vs 2.0%, p=0.004), or as a co-author (34.0% vs 15.7%, p=0.001). Conclusions: Academic CT surgeons who published a first-author BSR paper during training exhibit enhanced research productivity and scholarly impact. Funding and institutional support for aspiring CT surgeon-scientists may yield career-long academic benefits.

There is a very high prevalence of iron deficiency anemia in patients with systolic heart failure. The present study is a prospective, parallel, 1:1 randomized controlled trial of intravenous ferric-carboxy maltose compared with standard of care in patients with heart failure. A total of 70 patients who presented to us with symptomatic chronic heart failure were included and randomly assigned to either groups (35 per group). Post 12 weeks, there were improvements noticed in peak VO2, New York Heart Association functional classification, 6-min walk test distance covered and reduction in Minnesota Living with Heart Failure Questionnaire score in the ferric-carboxy maltose as compared with standard of care group. However, no improvement in ejection fraction was noticed., Lay abstract Iron deficiency is commonly seen in patients with heart failure. This study was performed to observe the effect of intravenous iron therapy (ferric-carboxy maltose) in this population. The outcome showed significant benefit in symptoms and improvement in quality of life. These results are in concordance with other similar trials. Therefore, simple intravenous iron replacement along with other heart failure measures can make life easier for patients with heart failure.

Acne is a multifactorial skin disease, underpinned by colonization of Propionibacterium acnes and inflammation. The emergence of resistant P. acnes strains has affected the current acne treatment algorithm. This setback served as an impetus for rationally designing a library of next-generation antibiotics that exhibit a bactericidal effect on resistant P. acnes and exert an immunomodulatory function to reduce inflammation. In silico screening showed that one of the molecules, VCD-004, exhibits improved mode of binding to bacterial DNA gyrase. VCD-004 shows high potency against clinical isolates of resistant P. acnes and excellent efficacy in vivo. Furthermore, VCD-004 exhibits a superior mutant prevention index, suggesting that it impedes the development of resistance better than clindamycin. Additionally, it shows optimal skin penetration and has a potent anti-inflammatory effect via reduction of proinflammatory cytokines (IL-6) independent of its antibacterial action. VCD-004 affects P. acnes-induced nuclear accumulation of NF-κB in THP-1 cells. The in vitro viability of human keratinocytes in the presence of VCD-004 indicates a desirable therapeutic window for topical use. Such rationally designed bactericidal and immunomodulatory dual pharmacophore-based lipophilic molecule(s) can emerge as the next-generation topical therapy for acne with underlying resistant P. acnes etiology.

A 5-year-old girl presented with decreased vision and outward deviation of her right eye. Fundus examination revealed multiple hard exudates in the macula in the right eye and nasal to the disk in the left eye. The patient was lost to follow-up in the near term but presented 9 months later with reduced vision and an increase in exudates in both eyes. RetCam fluorescein angiography confirmed the diagnosis of bilateral Coats disease.

Research regarding the definition and consequences of dieting has generated controversy for years. This controversy has spilled over into the public domain, especially as eating disorders and obesity have become more prevalent. One of the earliest and longest-lasting controversies involves the restrained eating framework, which was originally developed by Herman and Polivy and also strongly influenced the development of the cognitive-behavioral model of bulimia nervosa. An alternative framework for understanding the role of dieting in nonclinical and clinical groups, called the Three-Factor Model of Dieting, took a sharply different approach to defining, and understanding the impact of, dieting. This paper provides a brief historical review of the development of these divergent perspectives and updates the Three Factor Model's critical distinction between restraining eating to prevent over-consumption and dieting to lose weight. We suggest that three historical trends impacted the development of Restraint Theory in ways that unfairly impugned dieting for weight control: the emergence of the new eating disorders of bulimia nervosa and binge eating disorder, a population-based increase in loss of control eating and a population-based increase in obesity. This update is aimed in part at encouraging new research to reconcile ongoing, unresolved issues between Herman and Polivy's restrained eating model and the Three-Factor model of Dieting model. Such research might also contribute to the public's understanding of the pros and cons of dieting and to new approaches to treating eating disorders and obesity.

Purpose To determine ocular biometric and refractive profiles of premature children at risk of retinopathy of prematurity (ROP), comparing those who did and did not require laser treatment. Methods In this prospective study, premature infants underwent biometry and refraction with their first ROP examination. Study parameters were assessed again at 3 months, 6 months, and 1 year. The main outcome measures were spherical equivalent, axial length, and keratometry. Results A total of 122 infants (243 eyes) were included. At baseline, infants without ROP, those with ROP who never needed treatment, and those who later needed treatment had overall comparable axial length (P = 0.53) and myopia (P = 0.05); the highest severity group had higher corneal steepness and more myopia at baseline. At 1 year, children with laser-treated ROP had the shortest axial lengths, with the least decrease in keratometry, and the greatest increase in myopia (−2.0 D; P = 0.001). Anisometropia, if present initially, persisted through the 1-year examination. Mean refractive error was more myopic in zone 1 disease (P = 0.3) and in aggressive posterior ROP (P = 0.15). Conclusions Severe ROP is associated with disruption of emmetropization, and steeper corneas and more myopia at the first ROP examination, before any intervention. In our study cohort, these differences became more marked over the course of 1 year after laser therapy. The myopia in these cases was not axial. Laser therapy did not induce new anisometropia.

Purpose: To evaluate postoperative outcomes of cataract surgery in children with persistent hyperplastic primary vitreous (PHPV) and factors affecting outcomes. Methods: We analyzed 29 eyes of 28 children with PHPV presenting at a tertiary care center in northern India. All eyes underwent phacoaspiration followed by primary posterior capsulotomy with or without cauterization of persistent fetal vasculature under general anesthesia. Hydrophobic intraocular lens was implanted in selective cases. Postoperative outcomes such as clarity of visual axis, need for secondary surgical procedures, and complications were noted. Results: Out of a total of 28 children (16 male and 12 female), 27 were unilateral while 1 patient had bilateral involvement. Mean age at surgery was 25.14 months, ranging from 2 months to 144 months. Mean axial length of the globe at surgery was 19.66 ± 2.28 mm. Cataract surgery with intraocular lens implantation was done in 22 eyes whereas 7 were left aphakic. The most common intraoperative complication noted was intraoperative bleed in 11 eyes (37.9%) resulting in postoperative hyphema in 9 eyes (31%) and vitreous hemorrhage in 8 eyes (27.5%). Visual axis opacification was seen in 12 eyes and all required membranectomy. Three eyes developed glaucoma while retinal detachment was noted in 2 eyes and 1 of them became phthisical. Conclusions: Favorable outcome was more often achieved in anterior PHPV. Surgical outcomes in eyes with PHPV undergoing cataract surgery are limited by intraoperative and postoperative complications such as hyphema, vitreous hemorrhage, recurrent visual axis opacification, glaucoma, and retinal detachment.

Background E. faecalis (Efc) isolates are usually susceptible to ampicillin (AMP). AMP-based regimens are the standard of care for enterococcal infections, although other antibiotics are often used as definitive treatment. We thus compared outcomes of patients with cancer and Efc bacteremia treated with AMP-containing (ACR) and non-AMP-containing antibiotic regimens (NACR). Methods A multicenter, prospective, observational cohort study conducted at MD Anderson Cancer Center, Henry Ford Hospital, and Memorial Hermann Health System. Eligible patients were ≥ 18 years old, diagnosed with cancer, and had at least one Efc bloodstream isolate collected from 12/2015 to 12/2018. Patients with polymicrobial infections were excluded. Patients were divided into two groups: i) ACR and ii) NACR. ACR included patients who received AMP at any time during treatment; other antimicrobials were permitted. NACR patients did not receive AMP at any time. The primary outcome compared desirability of outcome ranking (DOOR) between ACR and NACR at day 14. The DOOR consisted of six hierarchical levels: 1 - death; 2 - inpatient without microbiological cure (MC) and with acute kidney injury (AKI); 3 - inpatient without MC and without AKI; 4 - inpatient admitted with MC and with AKI; 5 - inpatient with MC and without AKI; 6 - alive and discharged. Comparison of DOORs between ACR and NACR was performed using inverse probability of treatment weighted (IPTW) ordered logistic regression. Results Seventy-one patients were included (ACR, n = 35; NACR, n = 36). No difference was seen in DOORs at day 14 between ACR and NACR (odds ratio [OR] 1.14, 95% Confidence Interval [CI] 0.45 – 2.92, p=0.78). No difference was observed for all-cause mortality at day 14 (OR 0.6, 95% CI 0.09 – 3.77, p=0.58) or day 30 (OR 0.42, 95% CI 0.09 – 1.94, p=0.27). Patients treated with ACR received a lower median duration of other antibiotics at any point during treatment compared to NACR: daptomycin (2 v 4 days) vancomycin (2 v 4 days), and linezolid (1 v 2 days). Conclusion Patients with cancer and Efc bloodstream infections had similar outcomes when treated with ACR and NACR. ACR were associated with less use of broad-spectrum antimicrobials. Future research should focus on the ecologic impact of use of NACR. Disclosures Marcus Zervos, MD, Melinta Therapeutics (Grant/Research Support) Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)

PURPOSE To evaluate the feasibility and utility of microscope-integrated optical coherence tomography in patients undergoing full-thickness neurosensory retinal autograft for refractory macular hole (MH)-associated retinal detachment. METHODS We analyzed two eyes of two patients who had undergone a neurosensory retinal autograft for large MH associated retinal detachment. Both cases had microscope-integrated optical coherence tomography-guided placement and sizing of the retinal autograft. Time taken for obtaining microscope-integrated optical coherence tomography images, morphology of the retinal autograft (intraoperative and postoperative), and anatomic and functional outcomes were noted. RESULTS The first case had optic disc pit-related maculopathy with a large MH and total retinal detachment. She had undergone a vitrectomy with internal limiting membrane peeling elsewhere. The second patient had a treatment-naive large MH with total retinal detachment. Both patients underwent vitrectomy with microscope-integrated optical coherence tomography-guided autologous neurosensory retinal autograft placement and silicone oil tamponade. At 6 months and 3 months follow-up, respectively, both patients had closed MHs, attached retinas, and improvement in visual acuity. CONCLUSION Microscope-integrated optical coherence tomography provides intraoperative visualization of MHs and provides real-time feedback regarding dimensions of the retinal autograft, thus aiding in accurate sizing of the graft. This ensures that the autograft fits snugly in the MH, thereby restoring macular structure and improving visual acuity.

Determinants of binge eating are usually understood in terms of cognitive, behavioral, and affective disturbances. However, many of those with eating disorders (EDs) experienced elevated premorbid weights, lost substantial weight as their disorder developed and/or are currently at low weight. We review evidence that these three aspects of weight regulation are related to binge eating, to loss of control eating in the absence of objective binge eating and/or to positive energy balance and weight gain over time (an outcome that is greatly feared in those with EDs). Thus, there appear to be powerful reciprocal influences between psychological and biological aspects of binge eating but until recently only the psychological features have been incorporated into models of ED psychopathology and treatment. Further, several studies have shown that weight suppression is also related to eating symptoms in nonclinical groups, which indicates that elevated weight suppression can accelerate weight regain and have other negative impacts in the absence of an ED. In sum, the impact of weight history on the perpetuation of EDs indicates that treatment researchers should consider this impact as they try to improve treatment outcomes.

Balanced activity of kinases and phosphatases downstream of the BCR is essential for B cell differentiation and function and is disturbed in chronic lymphocytic leukemia (CLL). In this study, we employed IgH.TEμ mice, which spontaneously develop CLL, and stable EMC CLL cell lines derived from these mice to explore the role of phosphatases in CLL. Genome-wide expression profiling comparing IgH.TEμ CLL cells with wild-type splenic B cells identified 96 differentially expressed phosphatase genes, including SH2-containing inositol phosphatase (Ship2). We found that B cell–specific deletion of Ship2, but not of its close homolog Ship1, significantly reduced CLL formation in IgH.TEμ mice. Treatment of EMC cell lines with Ship1/2 small molecule inhibitors resulted in the induction of caspase-dependent apoptosis. Using flow cytometry and Western blot analysis, we observed that blocking Ship1/2 abrogated EMC cell survival by exerting dual effects on the BCR signaling cascade. On one hand, specific Ship1 inhibition enhanced calcium signaling and thereby abrogated an anergic response to BCR stimulation in CLL cells. On the other hand, concomitant Ship1/Ship2 inhibition or specific Ship2 inhibition reduced constitutive activation of the mTORC1/ribosomal protein S6 pathway and downregulated constitutive expression of the antiapoptotic protein Mcl-1, in both EMC cell lines and primary IgH.TEμ CLL cells. Importantly, also in human CLL, we found overexpression of many phosphatases including SHIP2. Inhibition of SHIP1/SHIP2 reduced cellular survival and S6 phosphorylation and enhanced basal calcium levels in human CLL cells. Taken together, we provide evidence that SHIP2 contributes to CLL pathogenesis in mouse and human CLL.

Background Metabolic complications are highly prevalent in cancer survivors treated with irradiation but the underlying mechanisms remain unknown. Methods Chow or high fat-fed C57Bl/6J mice were irradiated (6Gy) before investigating the impact on whole-body or skeletal muscle metabolism and profiling their lipidomic signature. Using a transgenic mouse model (Tg:Pax7-nGFP), we isolated muscle progenitor cells (satellite cells) and characterised their metabolic functions. We recruited childhood cancer survivors, grouped them based on the use of total body irradiation during their treatment and established their lipidomic profile. Results In mice, irradiation delayed body weight gain and impaired fat pads and muscle weights. These changes were associated with impaired whole-body fat oxidation in chow-fed mice and altered ex vivo skeletal muscle fatty acid oxidation, potentially due to a reduction in oxidative fibres and reduced mitochondrial enzyme activity. Irradiation led to fasting hyperglycaemia and impaired glucose uptake in isolated skeletal muscles. Cultured satellite cells from irradiated mice showed decreased fatty acid oxidation and reduced glucose uptake, recapitulating the host metabolic phenotype. Irradiation resulted in a remodelling of lipid species in skeletal muscles, with the extensor digitorum longus muscle being particularly affected. A large number of lipid species were reduced, with several of these species showing a positive correlation with mitochondrial enzymes activity. In cancer survivors exposed to irradiation, we found a similar decrease in systemic levels of most lipid species, and lipid species that increased were positively correlated with insulin resistance (HOMA-IR). Conclusion Irradiation leads to long-term alterations in body composition, and lipid and carbohydrate metabolism in skeletal muscle, and affects muscle progenitor cells. Such changes result in persistent impairment of metabolic functions, providing a new mechanism for the increased prevalence of metabolic diseases reported in irradiated individuals. In this context, changes in the lipidomic signature in response to irradiation could be of diagnostic value.

There is an ongoing need for clinically relevant models of perinatal infection and hypoxia-ischemia (HI) in which to test therapeutic interventions for infants with the neurological sequela of prematurity. Ferrets are ideal candidates for modeling the preterm human brain, as they are born lissencephalic and develop gyrencephalic brains postnatally. At birth, ferret brain development is similar to a 13 week human fetus, with postnatal-day (P) 17 kits considered to be equivalent to an infant at 32-36 weeks' gestation. We describe an injury model in the P17 ferret, where lipopolysaccharide administration is followed by bilateral cerebral ischemia, hypoxia, and hyperoxia. This simulates the complex interaction of prolonged inflammation, ischemia, hypoxia, and oxidative stress experienced in a number of neonates who develop brain injury. Injured animals display a range of gross injury severity, with morphological changes in the brain including narrowing of multiple cortical gyri and associated sulci. Injured animals also show slowed reflex development, slower and more variable speed of locomotion in an automated catwalk, and decreased exploration in an open field. This model provides a platform in which to test putative therapies for infants with neonatal encephalopathy associated with inflammation and HI, study mechanisms of injury that affect cortical development, and investigate pathways that provide resilience in unaffected animals.

Multi-drug-resistant tuberculosis (TB) is a major public health problem, concerning about half a million cases each year. Patients hardly adhere to the current strict treatment consisting of more than 10 000 tablets over a 2-year period. There is a clear need for efficient and better formulated medications. We have previously shown that nanoparticles made of cross-linked poly-β-cyclodextrins (pβCD) are efficient vehicles for pulmonary delivery of powerful combinations of anti-TB drugs. Here, we report that in addition to being efficient drug carriers, pβCD nanoparticles are endowed with intrinsic antibacterial properties. Empty pβCD nanoparticles are able to impair Mycobacterium tuberculosis (Mtb) establishment after pulmonary administration in mice. pβCD hamper colonization of macrophages by Mtb by interfering with lipid rafts, without inducing toxicity. Moreover, pβCD provoke macrophage apoptosis, leading to depletion of infected cells, thus creating a lung microenvironment detrimental to Mtb persistence. Taken together, our results suggest that pβCD nanoparticles loaded or not with antibiotics have an antibacterial action on their own and could be used as a carrier in drug regimen formulations effective against TB., SCOPUS: ar.j, info:eu-repo/semantics/published

Purpose: To report epidemiology of uveitis in a tertiary-care referral institute in North India.Methods: Hospital records of patients with uveitis between June 2011 and September 2014 were retrospectively analyzed.Results: Of the 1912 patients, 56.64% were males. Anterior uveitis (43.04%) was the most common manifestation followed by posterior uveitis (24.58%), panuveitis (16.21%), and intermediate uveitis (10.66%). Specific etiologies could be ascertained in 60.56%. Tuberculosis (22.9%) was the most common infectious and HLA-B27-associated uveitis (9.46%) among non-infectious causes.Conclusions: There is a trend towards a decrease in idiopathic etiologies of uveitis. Tuberculosis remains the most common infectious etiology in North India.

Exposure to ionizing radiation increases the risk of chronic metabolic disorders such as insulin resistance and type 2 diabetes later in life. We hypothesized that irradiation reprograms the epigenome of metabolic progenitor cells, which could account for impaired metabolism after cancer treatment. C57Bl/6 mice were treated with a single dose of irradiation and subjected to high-fat diet (HFD). RNA sequencing and reduced representation bisulfite sequencing were used to create transcriptomic and epigenomic profiles of preadipocytes and skeletal muscle satellite cells collected from irradiated mice. Mice subjected to total body irradiation showed alterations in glucose metabolism and, when challenged with HFD, marked hyperinsulinemia. Insulin signaling was chronically disrupted in skeletal muscle and adipose progenitor cells collected from irradiated mice and differentiated in culture. Epigenomic profiling of skeletal muscle and adipose progenitor cells from irradiated animals revealed substantial DNA methylation changes, notably for genes regulating the cell cycle, glucose/lipid metabolism, and expression of epigenetic modifiers. Our results show that total body irradiation alters intracellular signaling and epigenetic pathways regulating cell proliferation and differentiation of skeletal muscle and adipose progenitor cells and provide a possible mechanism by which irradiation used in cancer treatment increases the risk for metabolic disease later in life.

To describe optical coherence tomography angiography (OCTA) features of lesions of tubercular multifocal serpiginoid choroiditis (TB MSC) that developed paradoxical worsening (PW).In this prospective study, subjects with TB MSC who developed PW upon initiation of anti-tubercular therapy were included. Multimodal imaging was performed using OCTA, enhanced-depth imaging OCT, fluorescein angiography (FA), and indocyanine green angiography (ICGA). Morphologic changes in the retinochoroidal vasculature during progression of TB MSC were assessed on OCTA.Five subjects (4 males, 1 female) were included in the study. PW of the lesions was associated with increased areas of choriocapillaris flow void on en face OCTA in all eyes. The lesions showed partial healing in the center and continuous progression at the active edges. Two eyes showed development of vascular tufts on OCTA as the lesions progressed.OCTA provides high-resolution imaging of progressive choriocapillaris hypoperfusion among TB MSC patients developing PW of the disease.

Various signal transduction pathways have been implicated in the pathogenesis of chronic lymphocytic leukemia (CLL), which is characterized by the progressive accumulation of monoclonal CD5(+) B cells in the blood. B cell receptor (BCR) signaling appears to have a crucial role in disease onset and is thought to be induced by self or non-self-antigen recognition leading to chronic stimulation. Several of the kinases functioning downstream of the BCR are aberrantly expressed or constitutively activated in CLL. Yet, these kinases have additional roles, particularly in chemokine receptor signaling, which is essential for homing and survival of CLL cells in lymphoid organs, or in toll-like receptor signaling. Recently, small molecule inhibitors of kinases in the BCR signaling pathway have shown impressive anti-tumor activity in clinical trials. Remarkably, the observed durable responses in CLL patients were accompanied by transient increases in blood lymphocyte numbers, indicating the importance of these kinases in chemokine receptor signaling. In this review, we therefore highlight the role of BCR signaling and the important other associated signal transduction cascades for CLL cells and give an overview of novel agents that target these specific pathways and were shown to be successful for CLL treatment in clinical trials.

Acne vulgaris is a multifactorial skin disease associated with the colonization of Propionibacterium acnes. Antibiotics are a mainstay of treatment for acne, yet the emergence of resistance against the currently approved antibiotics is a serious concern. In this case report, a slow responder had multiple Propionibacterium acnes isolates with varied levels of sensitivity to the conventional antibiotics. The bacterial isolates obtained from acne samples collected from the patient were analyzed for phylogeny, and was found to be largely restricted to two different lineage patterns. Propionibacterium acnes phylotype IA1, which is considered to be pathogenic, displayed clindamycin sensitivity, but phylotype IB, which is associated with commensals, exhibited high clindamycin resistance. Sensitivity analysis revealed uniform resistance to macrolides, but susceptibility to tetracycline and nadifloxacin. These results implicate Propionibacterium acnes in the pathophysiology of acne vulgaris, although the lines between commensal and pathological phylotypes may be blurred. Switching the patient to a combination of minocycline and nadifloxacin resulted in a significant improvement in the clinical lesions. Such a science-driven judicious selection of antibiotics can minimize the probability of development of resistance, and might be the way forward in the treatment of acne.

We describe a surgical technique for the correction of isolated congenital lenticular coloboma associated with high corneal astigmatism. Transscleral fixation of the capsular bag with a single eyelet Cionni capsular tension ring was followed by in-the-bag implantation of a toric intraocular lens (IOL). This lead to complete correction of the lenticular defect and perfect alignment of the toric lens. In this case, the child attained an unaided distance visual acuity of 20/30 following amblyopia therapy and a well-aligned toric IOL at 12 months of follow-up. This technique can be used in cases with concomitant lenticular coloboma and significant corneal astigmatism.