Statins are Associated With Increased Biochemical Recurrence After Radical Prostatectomy in Diabetic Men but no Association was Seen in Men also Taking Metformin: Results From the SEARCH Database

Purpose

To investigate the preoperative use of combination metformin and statin versus monotherapy on biochemical recurrence (BCR) after radical prostatectomy (RP) in diabetic men.

Uveitis in Patients Treated with CTLA-4 and PD-1 Checkpoint Blockade Inhibition

ABSTRACT

Purpose: To investigate the link between treatment with CTLA-4 and PD-1 checkpoint blockade inhibitors and the development of noninfectious uveitis.

Methods: A survey was distributed to uveitis specialists to identify patients who developed uveitis while receiving either PD-1 inhibitors pembrolizumab and nivolumab; PD-L1 inhibitors atezolizumab, avelumab, and durvalumab; or the CTLA-4 inhibitor ipilimumab.

Results: Fifteen patients from seven institutions were identified. The most common cancer diagnosis (13/15) was malignant melanoma. Fourteen patients had a new uveitis diagnosis following checkpoint blockade administration (six anterior uveitis, six panuveitis, one posterior uveitis, one anterior/intermediate combined); one patient developed optic neuritis. Uveitis was diagnosed within 6 months after drug initiation for 11/12 patients (median 63 days). Corticosteroid treatment was effective for most patients, although two patients had permanent loss of vision.

Conclusions: Patients on checkpoint inhibitor therapy should be educated to seek care if they develop ocular symptoms, and prompt referral to specialists should be incorporated into oncology protocols.     

Opioid overdose prevention education for medical students: Adopting harm reduction into mandatory clerkship curricula

Abstract

Background: Opioid overdose deaths constitute a public health crisis in the United States. Strategies for reducing opioid-related harm are underutilized due in part to clinicians’ low knowledge about harm reduction theory and limited preparedness to prescribe naloxone. Educational interventions are needed to improve knowledge and attitudes about, and preparedness to address, opioid overdoses among medical students. Methods: Informed by the Department of Veterans Affairs’ Overdose Education and Naloxone Distribution (OEND) program and narrative medicine, we developed and led a mandatory workshop on harm reduction for clerkship medical students. Using validated scales, we assessed students’ knowledge and attitudes about, and preparedness to address, opioid overdoses before the workshop and 6 weeks after. Results: Of 75 participating students from February through December 2017, 55 (73%) completed pre-workshop and 38 (51%) completed both pre- and post-workshop surveys. At baseline, 40 (73%) encountered patients with perceived at-risk opioid use in the previous 6 weeks, but only 11 (20%) recalled their teams prescribing naloxone for overdose prevention. Among those completing both surveys, knowledge about and preparedness to prevent overdose showed large improvement (Cohen’s d?=?0.85, P?<?.001; Cohen’s d?=?1.24, P?<?.001, respectively) and attitudes showed moderate improvement (Cohen’s d?=?0.32, P = .04). Discussion: Educational interventions grounded in harm reduction theory can increase students’ knowledge and attitudes about, and preparedness to address, opioid overdoses.     

Patterns of Uveitis among Patients Attending Jimma University Department of Ophthalmology,Jimma, Ethiopia

ABSTRACT

Introduction: Uveitis is an important cause of blindness and ocular morbidity in the world. The patterns of uveitis have not been well characterized in sub-Saharan Africa.

Purpose: To describe the characteristics of uveitis among patients presenting to Jimma University Department of Ophthalmology (JUDO) from July 2013 to December 2014.

Methods: This hospital-based prospective cross-sectional study included all new uveitis patients visiting JUDO outpatient department during the study period.

Results: Among 98 patients diagnosed with uveitis, anterior uveitis was found in 74.5% of patients. Majority of the patients, 83.7%, had unilateral uveitis. A uveitis syndrome was identified in 22.5% of cases; of these 15 (68.2%) were infectious. Herpes simplex uveitis was the commonest infectious cause (53.3%) while Toxoplasmosis was the most common cause of posterior uveitis (60%).

Conclusion: Anterior uveitis was the most common pattern found among uveitis patients. Herpes simplex and toxoplasmic chorioretinitis were the most common-identified infectious causes.     

IgA Nephropathy-Associated Uveitis: A Case Presentation

ABSTRACT

Purpose: To describe a case of bilateral panuveitis in the setting of IgA nephropathy.

Methods: Retrospective review of clinical records, fundus, and optical coherence tomographic (OCT) images, and fluorescein angiography.

Results: A 36-year-old female presented with IgA nephropathy and contemporaneous ocular manifestations of one-year duration. Clinical exam demonstrated bilateral panuveitis, 3+ anterior chamber (AC) cell in the right eye (OD), and 0.5+ AC cell in the left eye (OS). Funduscopic exam demonstrated diffuse yellow drusenoid deposits bilaterally (OU), accentuated on fundus autofluorescence as focal areas of hyperautofluorescence. Deposits correlated with retinal pigment epithelium hyper-reflectivity on OCT, and choroidal hypo-fluorescence on fluorescein angiography. The patient was managed with oral prednisone.

Conclusion: IgA nephropathy is a systemic autoimmune disease that may be associated with uveitis. Immunosuppression with corticosteroids appears to be an effective therapy.     

The Association Between Physical Activity and Cataracts Among 17,777 People Aged 15–69 Years Residing in Spain

ABSTRACT

Purpose

The aim of the present study was to assess the association between levels of physical activity (PA) and the presence of cataracts in people aged 15–69 years residing in Spain.     

Increasing the rate of the hydrogen evolution reaction in neutral water with protic buffer electrolytes

Electrocatalytic generation of H₂ is challenging in neutral pH water, where high catalytic currents for the hydrogen evolution reaction (HER) are particularly sensitive to the proton source and solution characteristics. A tris(hydroxymethyl)aminomethane (TRIS) solution at pH 7 with a [2Fe-2S]-metallopolymer electrocatalyst gave catalytic current densities around two orders of magnitude greater than either a more conventional sodium phosphate solution or a potassium chloride (KCl) electrolyte solution. For a planar polycrystalline Pt disk electrode, a TRIS solution at pH 7 increased the catalytic current densities for H₂ generation by 50 mA/cm² at current densities over 100 mA/cm² compared to a sodium phosphate solution. As a special feature of this study, TRIS is acting not only as the primary source of protons and the buffer of the pH, but the protonated TRIS ([TRIS-H]⁺) is also the sole cation of the electrolyte. A species that is simultaneously the proton source, buffer, and sole electrolyte is termed a protic buffer electrolyte (PBE). The structure–activity relationships of the TRIS PBE that increase the HER rate of the metallopolymer and platinum catalysts are discussed. These results suggest that appropriately designed PBEs can improve HER rates of any homogeneous or heterogeneous electrocatalyst system. General guidelines for selecting a PBE to improve the catalytic current density of HER systems are offered.

Molecular hydrogen (H₂), a clean-burning and energy-dense fuel source, has been widely discussed as an attractive way to store intermittent energy from solar and wind through water electrolysis (1, 2). Current commercial electrolyzers can be separated into two categories based on their operating pH. The first are acidic polymer electrolyte membrane electrolyzers that work best with rare and expensive platinum-based electrocatalysts for the hydrogen evolution reaction (HER) (3). The second are strongly alkaline electrolyzers that suffer from caustic basic reaction conditions (4). Neutral pH conditions with inexpensive catalysts composed of Earth-abundant elements are a target for practical solar-to-hydrogen fuel devices due to lower cost and fewer safety concerns (5), but achieving fast rates with mild overpotentials under neutral conditions remains a challenge (6–12). In the pH range from 5 to 9, the electrocatalytic activity of platinum (Pt) itself does not conform to the expected thermodynamic potential shift with pH dependence of −59 mV/pH (13). This is due to the low concentration of the hydronium ion in this pH range and a transition to water as the primary reactant, which has a higher thermodynamic requirement for hydrogen evolution (13). Studies of electrocatalysts using buffers to maintain the pH in this range and ionic salts such as potassium chloride (KCl) to provide ionic strength to ensure high solution conductivity have shown that the buffer can aid the HER activity, presumably by acting as a proton donor (6, 14–18). To extend the scope of water-soluble electrocatalysts, biopolymers and bioinspired metallopolymer catalysts have also been studied (7, 12, 17–26). Bren and coworkers recently reported particularly enlightening studies of the effects of buffer pK_a and structure on the mechanism of the hydrogen evolution reaction for cobalt minienzymes (17, 18).We recently reported a new metallopolymer catalyst system built around a customized [2Fe-2S] catalyst site with a bridging aryldithiolato ligand which exhibits remarkable catalytic activity, air stability, and chemical stability (21). The electrocatalytic mechanism of the [2Fe-2S] catalysts with aryldithiolato ligands is known from previous studies and these catalysts operate at rates of 10⁵ s⁻¹ and faster (27–30). The readily synthesized and water-soluble metallopolymer composed of tertiary amine side-chain groups, PDMAEMA-g-[2Fe-2S] (Fig. 1), approached the current density of Pt operating in neutral water under the same conditions and matched the Faradaic yield (97 ± 3%) (21). Although the detailed structural and mechanistic causality of these profound improvements for these metallopolymer electrocatalysts remain subjects of study, the nature of this molecular system is ideal for studying solution effects on the HER reaction at neutral pH for complexes that are normally insoluble in water. In the course of characterizing these electrocatalysts, solutions containing tris(hydroxymethyl)aminomethane (TRIS) at pH 7 were discovered to be exceptionally advantageous to the catalytic rate. In contrast to the few previous studies of TRIS buffer with electrocatalysts (14, 15, 18), we utilized TRIS at a high concentration. At pH 7, TRIS is sufficiently in the cationic protonated form that additional electrolyte such as KCl is not needed for conductance. This important distinction from conventional studies allows TRIS to simultaneously play the roles of pH buffer, proton source, and sole electrolyte. There is precedence in employing buffers in a manner in which they are the sole electrolyte (7, 31–34). Referring to such species simply as a “buffer” or as an “electrolyte” is inadequate in representing the three functions including proton source. For the purposes of this paper we term a species that serves all three functions a protic buffer electrolyte (PBE). In the following discussion, a TRIS PBE solution is one in which [TRIS-H]⁺Cl⁻ is the sole electrolyte and the cation is a proton source, and a sodium phosphate PBE solution is one in which Na⁺[H₂PO₄]⁻ is the sole electrolyte and the anion is a proton source.Open in a separate windowFig. 1.(A) Depiction of the 2e⁻ electrocatalytic HER with POEGMA-g-[2Fe-2S] and/or PDMAEMA-g-[2Fe-2S] metallopolymers using TRIS or sodium phosphate protic buffer electrolytes at pH 7. (B) Image of POEGMA-g-[2Fe-2S] with MW = 14,216 grown in silico. The [2Fe-2S] active site is in the center of the polymer, blue represents the polymer backbone, and the rest are the oligo(ethylene glycol) side chains. See SI Appendix for the details of modeling and a larger image.One of the key unanswered questions for these new catalyst systems is whether the metallopolymer composition (i.e., amine side-chain groups) or the PBEs are more important to afford this outstanding catalytic activity. Herein we study the effects of PBEs by comparing the HER performances of a standard platinum catalyst and a [2Fe-2S] metallopolymer catalyst in TRIS PBE solutions, sodium phosphate PBE solutions, and a KCl electrolyte solution without a PBE. For this study, nonionic water-soluble metallopolymers were used, which were made using oligo(ethylene glycol) side-chain groups on the polymer to avoid the possibility of contributing effects of the protonated amino groups of PDMAEMA-g-[2Fe-2S] referred to earlier. The metallopolymer catalyst used in this work is designated as POEGMA-g-[2Fe-2S] (Fig. 1). We previously reported that this water-soluble metallopolymer was largely inactive for H₂ electrocatalysis at neutral pH in phosphate buffer (22). The current findings suggest that the use of electrolytes composed of inexpensive cationic organic proton donors can be readily applied to any homogeneous or heterogeneous electrocatalyst system as a facile means to enhance HER activity.     

Heart-type fatty acid-binding protein: an overlooked cardiac biomarker

Abstract

Cardiac troponins (cTn) are currently the standard of care for the diagnosis of acute coronary syndromes (ACS) in patients presenting to the emergency department (ED) with chest pain (CP). However, their plasma kinetics necessitate a prolonged ED stay or overnight hospital admission, especially in those presenting early after CP onset. Moreover, ruling out ACS in low-risk patients requires prolonged ED observation or overnight hospital admission to allow serial measurements of c-Tn, adding cost. Heart-type fatty acid-binding protein (H-FABP) is a novel marker of myocardial injury with putative advantages over cTn. Being present in abundance in the myocellular cytoplasm, it is released rapidly (<1?h) after the onset of myocardial injury and could potentially play an important role in both earlier diagnosis of high-risk patients presenting early after CP onset, as well as in risk-stratifying low-risk patients rapidly. Like cTn, H-FABP also has a potential role as a prognostic marker in other conditions where the myocardial injury occurs, such as acute congestive heart failure (CHF) and acute pulmonary embolism (PE). This review provides an overview of the evidence examining the role of H-FABP in early diagnosis and risk stratification of patients with CP and in non-ACS conditions associated with myocardial injury.

• Key messages

• Heart-type fatty acid-binding protein is a biomarker that is elevated early in myocardial injury

• The routine use in the emergency department complements the use of troponins in ruling out acute coronary syndromes in patients presenting early with chest pain

• It also is useful in risk stratifying patients with other conditions such as heart failure and acute pulmonary embolism.

     

Effects of boron-containing compounds on immune responses: review and patenting trends

Introduction: Boron-containing compounds induce effects on immune responses. Such effects are interesting to the biomedical field for the development of therapeutic tools to modulate the immune system.

Areas covered: The scope of BCC use to modify immune responses is expanding, mainly with regard to inflammatory diseases. The information was organized to demonstrate the breadth of reported effects. BCCs act as modulators of innate and adaptive immunity, with the former including regulation of cluster differentiation and cytokine production. In addition, BCCs exert effects on inflammation induced by infectious and noninfectious agents, and there are also reports regarding their effects on mechanisms involving hypersensitivity and transplants. Finally, the authors discuss the beneficial effects of BCCs on pathologies involving various targets and mechanisms.

Expert opinion: Some BCCs are currently used as drugs in humans. The mechanisms by which these BCCs modulate immune responses, as well as the required structure–activity relationship for each observed mechanism of action, should be clarified. The former will allow for the development of improved immunomodulatory drugs with extensive applications in medicine. Patenting trends involve claims concerning the synthesis and actions of identified molecules with a defined profile regarding cytokines, cell differentiation, proliferation, and antibody production.     

Post-viral atopic airway disease: pathogenesis and potential avenues for intervention

Introduction: In early childhood, wheezing due to lower respiratory tract illness is often associated with infection by commonly known respiratory viruses such as respiratory syncytial virus (RSV) and human rhinovirus (RV). How respiratory viral infections lead to wheeze and/or asthma is an area of active research.

Areas covered: This review provides an updated summary of the published information on the development of post-viral induced atopy and asthma and the mechanisms involved. We focus on the contribution of animal models in identifying pathways that may contribute to atopy and asthma following respiratory virus infection, different polymorphisms that have been associated with asthma development, and current options for disease management and potential future interventions.

Expert commentary: Currently there are no prophylactic therapies that prevent infants infected with respiratory viruses from developing asthma or atopy. Neither are there curative therapies for patients with asthma. Therefore, a better understanding of genetic factors and other associated biomarkers in respiratory viral induced pathogenesis is important for developing effective personalized therapies.