Background Mohs Micrographic Surgery (MMS) with melanoma antigen recognized by T cells (MART-1) immunostaining is an effective treatment for cutaneous melanoma. Objective Determine the efficacy of MMS with MART-1 immunostains in the management of invasive and in-situ melanoma. Methods and Materials A retrospective cohort study evaluated 2, 114 melanomas in 1,982 patients excised using MMS and MART-1 immunostains. Margins required for excision were calculated based on Breslow thickness, location and size. Survival and local recurrence rates were calculated and compared with those of historical controls. Results The mean follow-up was 3.73 years. Local recurrence was identified in 0.49 % (7/1,419) of primary melanomas. ~82% of melanomas were excised with ≤6mm margins. The surgical margin was significantly related to tumor location and size, but not to Breslow thickness. The five-year Kaplan-Meier local recurrence and disease-specific survival were 0.59 ± 0.30 and 98.53 ± 0.42, respectively. MMS with MART-1 immunostains achieved lower local recurrence rates, and equivalent or higher Kaplan-Meier survival rates when compared with conventional wide local excision. Conclusion MMS with MART-1 immunostain is an effective treatment for melanoma as evidenced by low local recurrence rates. It offers the advantage of more tissue conserving margins than those recommended for conventional excision.

Background and Objectives: The cannabinoid receptor 2 (CB2) was previously implicated in brain functions, including complex behaviors. Here, we assessed the role of CB2 in selected swimming behaviors in zebrafish larvae and developed an in vivo upscalable whole-organism approach for CB2 ligand screening. Experimental Approach: Using CRISPR-Cas9 technology, we generated a novel null allele ( cnr2 upr1 ) and a stable homozygote-viable loss-of-function (CB2-KO) line. We measured in untreated wild-type and cnr2 upr1/upr1 larvae, photo-dependent (swimming) responses (PDR) and center occupancy (CO) to establish quantifiable anxiety-like parameters. Next, we measured PDR alteration and CO variation while exposing wild-type and mutant animals to an anxiolytic drug (valproic acid [VPA]) or to an anxiogenic drug (pentylenetetrazol [PTZ]). Finally, we treated wild-type and mutant larvae with two CB2-specific agonists (JWH-133 and HU-308) and two CB2-specific antagonists, inverse agonists (AM-630 and SR-144528). Results: Untreated CB2-KO showed a different PDR than wild-type larvae as well as a decreased CO. VPA treatments diminished swimming activity in all animals but to a lesser extend in mutants. CO was strongly diminished and even more in mutants. PTZ-induced inverted PDR was significantly stronger in light and weaker in dark periods and the CO lower in PTZ-treated mutants. Finally, two of four tested CB2 ligands had a detectable activity in the assay. Conclusions: We showed that larvae lacking CB2 behave differently in complex behaviors that can be assimilated to anxiety-like behaviors. Mutant larvae responded differently to VPA and PTZ treatments, providing in vivo evidence of CB2 modulating complex behaviors. We also established an upscalable combined genetic/behavioral approach in a whole organism that could be further developed for high-throughput drug discovery platforms.

RationaleEthnopharmacology has documented hundreds of psychoactive plants awaiting exploitation for drug discovery. A robust and inexpensive in vivo system allowing systematic screening would be critical to exploiting this knowledge.ObjectiveThe objective of this study was to establish a cheap and accurate screening method which can be used for testing psychoactive efficacy of complex mixtures of unknown composition, like plant crude extracts.MethodsWe used automated recording of zebrafish larval swimming behavior during light vs. dark periods which we reproducibly altered with an anxiogenic compound, pentylenetetrazole (PTZ). First, we reversed this PTZ-altered swimming by co-treatment with a well-defined synthetic anxiolytic drug, valproic acid (VPA). Next, we aimed at reversing it by adding crude root extracts of Valeriana officinalis (Val) from which VPA was originally derived. Finally, we assessed how expression of neural activity-regulated genes (c-fos, npas4a, and bdnf) known to be upregulated by PTZ treatment was affected in the presence of Val.ResultsBoth VPA and Val significantly reversed the PTZ-altered swimming behaviors. Noticeably, Val at higher doses was affecting swimming independently of the presence of PTZ. A strong regulation of all three neural-activity genes was observed in Val-treated larvae which fully supported the behavioral results.ConclusionsWe demonstrated in a combined behavioral-molecular approach the strong psychoactivity of a natural extract of unknown composition made from V. officinalis. Our results highlight the efficacy and sensitivity of such an approach, therefore offering a novel in vivo screening system amenable to high-throughput testing of promising ethnobotanical candidates.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-016-4304-z) contains supplementary material, which is available to authorized users.

Purpose: To identify racial/ethnic disparities in utilization rates, in-hospital outcomes and health care resource use among Non-Hispanic Whites (NHW), African Americans (AA) and Hispanics undergoing transcatheter aortic valve replacement (TAVR) in the United States (US).

Background The conventional treatment for idiopathic intracranial hypertension involves weight loss, steroids, diuretics, and/or serial lumbar punctures; however, if the symptoms persist or worsen, surgical intervention is recommended. Surgical options include cerebrospinal fluid diversion procedures, such as ventriculoperitoneal and lumboperitoneal shunts, and optic nerve decompression with nerve sheath fenestration. The latter can be carried out using an endoscopic approach, but the outcomes of this technique have not been firmly established. Methods This systematic review examined the outcomes of performing endoscopic optic nerve decompression (EOND) in patients with idiopathic intracranial hypertension (IIH). Six studies were included for a total of 34 patients. Results The patients presented with visual field disturbances [32 of 32 (100%)], visual acuity disruptions [33 of 34 (97.1%)], papilledema [26 of 34 (76.5%)], and persistent headache [30 of 33 (90.1%)]. The mean duration of the symptoms ranged from 7 to 32 months. Overall, the patients showed post-EOND improvement of the signs and symptoms associated with IIH, specifically visual field deficits (93.8%), visual acuity (85.3%), papilledema (81.4%), and headaches (81.8%). Interestingly, 11 cases showed postoperative improvement in their symptoms with bony decompression of the optic canal alone, without nerve sheath fenestration. The authors did not report any major adverse events or complications with this approach. Conclusion EOND appears to be a promising and safe surgical alternative for patients with IIH who fail to respond to medical treatment. Further studies are needed before we can attest to the clinical validity of this procedure.

ObjectiveThe American Academy of Ophthalmology recommends a maximum hydroxychloroquine (HCQ) dose of ≤5.0 mg/kg/day to reduce the risk of HCQ-induced retinopathy. To determine if this dose adjustment would have an impact on the clinical course of SLE, we compared outcome measures in a cohort of patients with SLE before and after adjusting HCQ dose.MethodsSixty Puerto Ricans with SLE (per 1997 American College of Rheumatology criteria) treated with HCQ who were changed to HCQ ≤5.0 mg/kg/day were studied. Visits were ascertained every 6 months for 2 years before and 2 years after HCQ dose adjustment (baseline visit). Disease activity (per Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)), SLE exacerbations, emergency room visits, hospitalisations, disease damage (per Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), corticosteroids exposure, prednisone dose and immunosuppressive drugs exposure were determined before and after HCQ dose change.ResultsAt baseline visit, the mean age was 43.8±15.1 years. All patients were women. The mean disease duration was 13.8±9.1 years. After HCQ dose adjustment, patients required a lower prednisone dose when compared with visits before HCQ dose reduction. No significant differences were observed for mean SLEDAI scores, lupus exacerbations, emergency room visits, hospitalisations, disease damage and exposure to immunosuppressive drugs before and after HCQ dose adjustment.ConclusionsThis study suggests that adjustment of daily HCQ dose to ≤5.0 mg/kg/day of actual body weight does not have a significant impact on the short-term and mid-term outcomes in this group of patients with SLE.

IntroductionMinority populations in the USA are disproportionately affected by cardiovascular conditions. Reduced responsiveness to clopidogrel among carriers of CYP2C19 variants has been reported in patients with either coronary artery disease (CAD) or acute coronary syndrome (ACS) after the percutaneous coronary intervention (PCI). Previous studies have evaluated CYP2C19 genotyping-guided antiplatelet therapy in selected populations; however, this has yet to be tested among Hispanics. Given the paucity of clinical research on CYP2C19 and antiplatelet clinical outcomes in Hispanics, our study will test the safety and efficacy of a genetic-driven treatment algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics.Methods and analysisThis is a multicentre, prospective, non-randomised clinical trial that proposes an assessment of pharmacogenomic-guided DAPT in post-PCI Caribbean Hispanic patients with ACS or CAD. We will recruit 250 patients to be compared with a matched non-concurrent cohort of 250 clopidogrel-treated patients (standard-of-care). Major adverse cardiovascular events (MACEs) such as all-cause death, myocardial infarction (MI), stroke, coronary revascularisation, stent thrombosis and bleedings over 6 months will be the study endpoints. Among the recruited, high-risk patients will be escalated to ticagrelor and low-risk patients will remain on clopidogrel. The primary objective is to determine whether genetic-guided therapy is superior to standard of care. The secondary objective will determine if clopidogrel treatment in low-risk patients is not associated with a higher rate of MACEs compared with escalated antiplatelet therapy in high-risk patients. Patients will be enrolled up to the group’s completion.Ethics and disseminationApproval was obtained from the Institutional Review Board of the University of Puerto Rico Medical Sciences Campus (protocol # A4070417). The study will be carried out in compliance with the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice Guidelines. Findings will be published in a peer-reviewed journal and controlled access to experimental data will be available.Trial registration numberNCT03419325; Pre-results.

Objective:Infections are a major cause of morbidity and mortality in systemic lupus erythematosus. Clinical outcomes of systemic lupus erythematosus patients hospitalized due to infections vary among different ethnic populations. Thus, we determined the outcomes and associated factors in a group of Hispanics from Puerto Rico with systemic lupus erythematosus admitted due to severe infections.Methods:Records of systemic lupus erythematosus patients admitted to the Adult University Hospital, San Juan, Puerto Rico, from January 2006 to December 2014 were examined. Demographic parameters, lupus manifestations, comorbidities, pharmacologic treatments, inpatient complications, length of stay, readmissions, and mortality were determined. Patients with and without infections were compared using bivariate and multivariate analyses.Results:A total of 204 admissions corresponding to 129 systemic lupus erythematosus patients were studied. The mean (standard deviation) age was 34.7 (11.6) years; 90% were women. The main causes for admission were lupus flare (45.1%), infection (44.0%), and initial presentation of systemic lupus erythematosus (6.4%). The most common infections were complicated urinary tract infections (47.0%) and soft tissue infections (42.0%). In the multivariate analysis, patients admitted with infections were more likely to have diabetes mellitus (odds ratio: 4.20, 95% confidence interval: 1.23–14.41), exposure to aspirin prior to hospitalization (odds ratio: 4.04, 95% confidence interval: 1.03–15.80), and higher mortality (odds ratio: 6.00, 95% confidence interval: 1.01–35.68) than those without infection.Conclusion:In this population of systemic lupus erythematosus patients, 44% of hospitalizations were due to severe infections. Patients with infections were more likely to have diabetes mellitus and higher mortality. Preventive and control measures of infection could be crucial to improve survival in these patients.