Overcoming Challenges to Treat Inadequate Response in Major Depressive Disorder.

​​ ​​ When a patient with major depressive disorder experiences inadequate response to an antidepressant, clinicians should employ measurement-based care strategies to improve outcomes. Evidence suggests that adjunctive therapies, such as the FDA-approved atypical antipsychotics, are efficacious when the initial treatment is well tolerated but not improving symptoms. Clinicians should consult guidelines, peer-reviewed journals, CME programs, and other sources to stay up-to-date with current and emerging treatments in this area.

Inadequate Response to Treatment in Major Depressive Disorder: Augmentation and Adjunctive Strategies.

​​​​ About 30%-50% of patients experience inadequate response to antidepressant therapy, and treatment choices for these patients include augmenting the antidepressant with another therapy, increasing the dose, switching to a different antidepressant, or combining antidepressants. Clinicians should tailor treatment strategies based on patients' response, tolerability, and disease severity. In this activity, augmentation and adjunctive strategies involving atypical antipsychotics, as well as off-label options including buspirone, stimulants, thyroid hormone, and lithium, are reviewed.

Comparison of the clinical and cost effectiveness of two management strategies (rehabilitation versus surgical reconstruction) for non-acute anterior cruciate ligament (ACL) injury: study protocol for the ACL SNNAP randomised controlled trial.

Background: Anterior cruciate ligament (ACL) rupture is a common knee injury that can lead to poor quality of life, decreased activity and increased risk of secondary osteoarthritis of the knee. Management of patients with a non-acute ACL injury can include a non-surgical (rehabilitation) or surgical (reconstruction) approach. However, insufficient evidence to guide treatment selection has led to high variation in treatment choice for patients with non-acute presentation of ACL injury.

Complexity and ultrastructure of infectious extracellular vesicles from cells infected by non-enveloped virus.

Enteroviruses support cell-to-cell viral transmission prior to their canonical lytic spread of virus. Poliovirus (PV), a prototype for human pathogenic positive-sense RNA enteroviruses, and picornaviruses in general, transport multiple virions en bloc via infectious extracellular vesicles, 100~1000 nm in diameter, secreted from host cells. Using biochemical and biophysical methods we identify multiple components in secreted microvesicles, including mature PV virions; positive-sense genomic and negative-sense replicative, template viral RNA; essential viral replication proteins; and cellular proteins.

Ion channels and the regulation of myogenic tone in peripheral arterioles.

Myogenic tone is a hall-mark feature of arterioles in the microcirculation. This pressure-induced, contractile activation of vascular smooth muscle cells (VSMCs) in the wall of these microvessels importantly contributes to the regulation and maintenance of blood pressure; blood flow to and within organs and tissues; and capillary pressure and fluid balance. Ion channels play a central role in the genesis and maintenance of myogenic tone.

Introduction to ion channels and calcium signaling in the microcirculation.

The microcirculation is the network of feed arteries, arterioles, capillaries and venules that supply and drain blood from every tissue and organ in the body. It is here that exchange of heat, oxygen, carbon dioxide, nutrients, hormones, water, cytokines, and immune cells takes place; essential functions necessary to maintenance of homeostasis throughout the life span. This chapter will outline the structure and function of each microvascular segment highlighting the critical roles played by ion channels in the microcirculation.

Addition of Androgen-Deprivation Therapy or Brachytherapy Boost to External Beam Radiotherapy for Localized Prostate Cancer: A Network Meta-Analysis of Randomized Trials.

Purpose: In men with localized prostate cancer, the addition of androgen-deprivation therapy (ADT) or a brachytherapy boost (BT) to external beam radiotherapy (EBRT) have been shown to improve various oncologic end points. Practice patterns indicate that those who receive BT are significantly less likely to receive ADT, and thus we sought to perform a network meta-analysis to compare the predicted outcomes of a randomized trial of EBRT plus ADT versus EBRT plus BT.

Materials And Methods: A systematic review identified published randomized trials comparing EBRT with or without ADT, or EBRT (with or without ADT) with or without BT, that reported on overall survival (OS).

Recognizing Inadequate Response in Patients With Major Depressive Disorder.

​​ ​​ Being able to recognize inadequate response to antidepressant treatment and distinguish it from treatment-resistant depression is key in order for clinicians to provide appropriate therapies. Although definitions vary, nonresponse is often defined as less than 25% improvement on a standardized rating scale, and partial response, as more than 25% but less than 50% improvement. Residual symptoms characteristic of inadequate response (less than 50% improvement) include low mood, anxiety, irritability, guilt, and somatic symptoms.

Implementing Measurement-Based Care to Determine and Treat Inadequate Response.

​​ Measurement-based care (MBC) is an important strategy in the treatment of patients with major depressive disorder who have inadequate antidepressant response. The rating scales used in MBC can assist clinicians at critical decision points, such as when to declare a treatment failure, what to do with partial improvement, and how long to continue successful treatment. Measurement has two benefits: it gives the clinician an objective basis for comparison of symptom severity over time, and it helps patients to have insight into their illness course.

Prostate Cancer Radiation Therapy Recommendations in Response to COVID-19.

Purpose: During a global pandemic, the benefit of routine visits and treatment of patients with cancer must be weighed against the risks to patients, staff, and society. Prostate cancer is one of the most common cancers radiation oncology departments treat, and efficient resource utilization is essential in the setting of a pandemic. Herein, we aim to establish recommendations and a framework by which to evaluate prostate radiation therapy management decisions.

Lung function in oil spill responders 4-6 years after the Deepwater Horizon disaster.

Oil spill response and clean-up (OSRC) workers were exposed to hazardous airborne chemicals following the 2010 disaster. The aim of this study was to evaluate lung function in workers 4-6 years following the disaster using a prospective cohort. Participants who completed two spirometry test sessions 1-3 years, and 4-6 years after the spill (N = 1,838) were included and forced expiratory volume in 1 s (FEV; ml), forced vital capacity (FVC; ml), and ratio (FEV/FVC; %) determined.

Performance of clinicopathologic models in men with high risk localized prostate cancer: impact of a 22-gene genomic classifier.

Background: Prostate cancer exhibits biological and clinical heterogeneity even within established clinico-pathologic risk groups. The Decipher genomic classifier (GC) is a validated method to further risk-stratify disease in patients with prostate cancer, but its performance solely within National Comprehensive Cancer Network (NCCN) high-risk disease has not been undertaken to date.

Methods: A multi-institutional retrospective study of 405 men with high-risk prostate cancer who underwent primary treatment with radical prostatectomy (RP) or radiation therapy (RT) with androgen-deprivation therapy (ADT) at 11 centers from 1995 to 2005 was performed.

Association of Presalvage Radiotherapy PSA Levels After Prostatectomy With Outcomes of Long-term Antiandrogen Therapy in Men With Prostate Cancer.

Importance: In men with recurrent prostate cancer, addition of long-term antiandrogen therapy to salvage radiotherapy (SRT) was associated with overall survival (OS) in the NRG/RTOG 9601 study. However, hormone therapy has associated morbidity, and there are no validated predictive biomarkers to identify which patients derive most benefit from treatment.

Objective: To examine the role of pre-SRT prostate-specific antigen (PSA) levels to personalize hormone therapy use with SRT.

Successful liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a fatal disorder characterized by progressive gastrointestinal dysmotility, peripheral neuropathy, leukoencephalopathy, skeletal myopathy, ophthalmoparesis, and ptosis. MNGIE stems from deficient thymidine phosphorylase activity (TP) leading to toxic elevations of plasma thymidine. Hematopoietic stem cell transplant (HSCT) restores TP activity and halts disease progression but has high transplant-related morbidity and mortality.

Evolving Role of Stereotactic Body Radiation Therapy in the Management of Spine Metastases: Defining Dose and Dose Constraints.

When treating solid tumor spine metastases, stereotactic high-dose-per-fraction radiation, given in a single fraction or in a hypofractionated approach, has proved to be a highly effective and safe therapeutic option for any tumor histology, in the setting of de novo therapy, as salvage treatment of local progression after previous radiation, and in the postoperative setting. There are variations in practice based on the clinical presentation, goals of therapy, as well as institutional preferences. As a biologically potent therapy, a thoughtful and careful attention to detail with patient selection, treatment planning, and delivery is crucial for treatment success.

Outcomes associated with surfactant in more mature and larger premature infants with respiratory distress syndrome.

Objective: Examine the effect of off-label surfactant on mortality and morbidity in more mature and larger premature infants diagnosed with respiratory distress syndrome (RDS).

Study Design: Cohort study of premature infants born at 30-36 weeks, birth weight > 2 kg, and a diagnosis of RDS. We compared the odds of mortality and morbidity between infants who were exposed vs unexposed to surfactant.

Paediatric and adolescent anterior cruciate ligament reconstruction surgery.

Aims: Anterior cruciate ligament (ACL) surgery in children and the adolescent population has increased steadily over recent years. We used a national database to look at trends in ACL reconstruction and rates of serious complications, growth disturbance, and revision surgery, over 20 years.

Methods: All hospital episodes for patients undergoing ACL reconstruction, under the age of 20 years, between 1 April 1997 and 31 March 2017, were extracted by procedure code from the national Hospital Episode Statistics (HES).

Surrogate Endpoints in Localized Prostate Cancer.

Randomized clinical trials assessing novel therapies in men with localized prostate cancer frequently require large patient numbers and more than a decade of follow-up to demonstrate improvements in overall survival. As the landscape of treatment options for prostate cancer is rapidly changing, clinical trials requiring long follow-up threaten to impede treatment improvements and run the risk of results being obsolete by the time that they are reported in publication. To address these issues, there has been tremendous interest in identifying an intermediate clinical endpoint that can be assessed earlier in the disease course to serve as a robust surrogate for overall survival in men with localized prostate cancer.

Acute Radiation-induced GI-ARS and H-ARS in a Canine Model of Mixed Neutron/Gamma Relative to Reference Co-60 Gamma Radiation: A Retrospective Study.

Studies performed decades ago in the canine and nonhuman primate established the dose response relationships for the hematopoietic acute radiation syndrome in response to mixed neutron/gamma, x-radiation, and Co gamma radiation. There were no published studies that determined the dose response relationships for the gastrointestinal acute radiation syndrome in response to either noted radiation quality. This analysis of a retrospective, unpublished study provided the dose response relationships in a canine model for the acute gastrointestinal syndrome relative to the acute hematopoietic syndrome due to mixed neutron/gamma radiation.

Inflammation-induced IgE promotes epithelial hyperplasia and tumour growth.

IgE is the least abundant circulating antibody class but is constitutively present in healthy tissues bound to resident cells via its high-affinity receptor, FcεRI. The physiological role of endogenous IgE antibodies is unclear but it has been suggested that they provide host protection against a variety of noxious environmental substances and parasitic infections at epithelial barrier surfaces. Here we show, in mice, that skin inflammation enhances levels of IgE antibodies that have natural specificities and a repertoire, VDJ rearrangements and CDRH3 characteristics similar to those of IgE antibodies in healthy tissue.

Hands Up, Now What?: Black Families' Reactions to Racial Socialization Interventions.

Given the heightened national attention to negative race-related issues and the subsequent community solution-oriented outcry (e.g., Black Lives Matter movement), it is crucial to address healing from racial discrimination for Black Americans.

Laparoscopic sleeve gastrectomy versus laparoscopic Roux-en-Y gastric bypass in the pediatric population: a MBSAQIP analysis.

Background: The growing prevalence of childhood obesity has resulted in an increased number of children and adolescents who undergo bariatric surgery. The safety of laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) remains controversial in the pediatric population.

Objective: To assess the safety of LSG compared with LRYGB in patients aged ≤21 years.

Toxoplasmosis in non-cardiac solid organ transplant recipients: A case series and review of literature.

The risk of toxoplasmosis in high-risk cardiac transplant recipients is well recognized prompting universal donor and candidate screening with administration of targeted post-transplant chemoprophylaxis in high-risk (D+/R-) cardiac transplant patients. In contrast, until recently, there have been neither well-defined recommendations nor consensus regarding toxoplasmosis preventive strategies among non-cardiac solid organ transplant recipients. We report 3 cases of post-transplant toxoplasmosis in non-cardiac transplant recipients (one lung and two liver); all 3 infections presumed to be donor-derived.