Purpose: Few studies have examined efficacy of near-peer, 1 one-on-one tutoring programs in medical school basic science courses. An early study reported that 84% of first-/second-year (M1/M2) students tutored in dyads received passing grades. 2 More recently, studies have reported: statistically significant changes in academic grades in tutored courses among osteopathic medical students most at risk of failing, 3 improved in-course assessment scores among tutored allopathic students who had previously failed, 4 and overall reduced failure rates in allopathic medical school. 5 The current study seeks to evaluate a one-on-one near-peer tutoring program open to all M1 students in 3 basic science courses at an allopathic medical school over 3 consecutive academic years (2016–2017, 2017–2018, and 2018–2019). Methods: Student scores (n = 639) on all in-course examinations were collected for each of the 3 academic years in the following courses: Gross Anatomy (5 exams), Histology/Cell Biology (5 exams), and Medical Physiology (4 exams). These data were electronically linked to admissions data (Medical College Admission Test [MCAT] scores, grade point average [GPA], multiple mini-interview and CASPer scores, demographics) and scores on the United States Medical Licensing Examination (USMLE) Step 1. Within each academic year, scores on each in-course assessment were standardized (i.e., z-scores). Separate repeated measures ANOVAs were conducted to compare students who received tutoring with those who did not with respect to changes in relative performance (i.e., z-scores) across assessments within each course. Step 1 scores were statistically regressed onto MCAT scores, and residual values (i.e., actual minus predicted Step 1 score) were compared by t tests between groups. Student t tests, chi-square statistics, and Pearson correlation coefficients were calculated to examine the relationships between admissions data, Step 1 scores, and participation in tutoring. Results: Tutored students had significantly lower MCAT and Step 1 scores; they were more likely to be female (77% vs 47%) and underrepresented in medicine (URiM; 23% vs 14%). There were no statistically significant differences among groups on the basis of undergraduate GPA, multiple mini-interview scores, or CASPer situational judgment test scores. The number of students receiving tutoring in each course over the 3 years studied were: Gross Anatomy (n = 103), Histology/Cell Biology (n = 68), and Medical Physiology (n = 66). When studied by academic year, with the exception of Histology/Cell Biology (P = .10) in 2017–2018, statistically significant gains in performance on exams over time, relative to peers in the same course, were observed for students who received tutoring. Nevertheless, mean final grades in each of these courses were significantly lower (P < .05) for tutored students than nontutored students. Overall, small but statistically significant correlations were observed between MCAT and Step 1 scores (only available for students tutored in 2016–2017 and 2017–2018; old MCAT: r = 0.35, P < .001; new MCAT: r = 0.27, P < .001). Analysis of residuals from regression analyses demonstrated that tutored students scored, on average, 3–5 points lower on Step 1 than was predicted by MCAT score, while nontutored students, on average, scored approximately 2 points higher than predicted based on MCAT. Discussion: Results suggest that near-peer tutoring was effective in improving student performance relative to classmates within courses in Anatomy, Histology/Cell Biology, and Medical Physiology. However, students tutored in these courses received significantly lower course grades and Step 1 scores. Female sex, URiM status, and lower MCAT scores were associated with greater likelihood of seeking tutoring. Significance: In a one-on-one near-peer tutoring program that is equally available to all students, lower-performing students were more likely to use services. While tutored students saw improved exam scores within courses, their overall performance was significantly lower than students who were not tutored. This suggests that tutoring programs support the improvement of lower-performing students within courses, but earlier and longer-term interventions need to be explored.

Post-inflammatory hyperpigmentation (PIH) is a reactive process resulting from increased melanin or abnormal distribution of melanin secondary to inflammatory skin conditions, dermatologic therapies, and external stimuli. Because PIH is a common condition that has a substantial effect on the quality of life, an understanding of its treatment modalities is essential. Though there are many therapeutic strategies for hyperpigmentary conditions such as melasma that are described in the literature, fewer studies focus on PIH. This article aims to provide a comprehensive literature review of therapies specifically used to treat PIH, such as topical combinations, chemical peels, and lasers. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.4887.

Immunoglobulin G4-related disease (IgG4-RD) is a chronic inflammatory condition characterized by IgG4+ plasma cell infiltration of the skin and other organs. Cutaneous forms of the disease may be under recognized owing to poorly defined diagnostic criteria and relatively recent recognition in the literature. The aim of this review is to describe the clinical, histological, and serological presentations of cutaneous IgG4-RD, and to provide an overview of its systemic manifestations for dermatologists. Cases of cutaneous IgG4-RD identified in the literature review were compared to control cases. Clinically, plaque morphology and systemic involvement of the orbit, submandibular gland, lacrimal gland, and parotid gland were associated with a diagnosis of cutaneous IgG4-RD. Histologically, lymphoplasmacytic infiltrate and percentage of IgG4+ plasma cells/IgG+ plasma cells > 40% were associated with the diagnosis. Serologically, neither elevated serum IgG4 nor IgE concentrations were associated with the diagnosis. Dermatologists should consider IgG4-RD as part of the differential diagnosis for nodules, papules, and plaques with an IgG4+ plasma cell infiltrate, especially in middle-aged and elderly males with systemic manifestations of the disease. Diagnosis requires thorough investigation of both cutaneous and systemic clinical and histological presentations.

Alopecia areata (AA) is a common non-scarring inflammatory hair loss disorder with an incompletely defined pathogenesis. Prior studies have examined familial expression of AA, but few cases in the literature describe concurrent presentation amongst siblings. Our case demonstrates the complex interplay between genetic and environmental factors in the development of alopecia areata within families.

Peer-assisted learning (PAL) is an educational method where students teach their peers. PAL has been increasingly integrated into medical education in various formats including near-peer tutoring (NPT), reciprocal-peer tutoring (RPT), and peer-to-peer tutoring. This review adds to current literature by focusing exclusively on outcomes from PAL peer tutoring programs implemented in conjunction with basic science courses in medical education. Although the programs differ in size, duration, course, resource availability, and method of evaluation and thus can be difficult to compare, PAL programs overall demonstrate benefits for both tutors and tutees and merit further investigation into optimal methods of implementation.

Scleromyxedema and lichen myxedematosus (LM) are rare disorders that fall along the spectrum of primary cutaneous mucinoses. Scleromyxedema is a systemic form that classically presents with generalized waxy papules, sclerodermoid eruption, and monoclonal gammopathy; LM is a localized form limited to the skin that classically presents with white, firm, waxy papules and lacks monoclonal gammopathy. According to diagnostic criteria established in 2001, the diagnosis of both conditions requires absence of thyroid disease. However, atypical cases that lack monoclonal gammopathy and that present with hypothyroidism have been reported, suggesting that these criteria may require revision. First, we report a case of a 58-year-old female with a history of Hashimoto thyroiditis and biopsy-proven scleromyxedema responsive to intravenous immunoglobulin therapy with delayed presentation of monoclonal gammopathy. Next, we report a case of a 54-year-old female with a history of hypothyroidism, Hodgkin’s lymphoma in remission after radiation and chemotherapy, and concurrent rheumatoid arthritis, with biopsy-proven LM temporarily responsive to systemic steroids. Our cases demonstrate that patients with papular mucinoses can have a multitude of concurrent and prior rheumatologic and endocrine conditions, including thyroid disease, which should not preclude a diagnosis of scleromyxedema and LM.

Dermatologists commonly prescribe medications such as antibiotics and corticosteroids that can increase the risk for candidiasis. Though conventional antifungals are often effective against candidiasis, they are not without side effects and species of Candida are gaining resistance. Probiotics help treat conditions such as post-antibiotic diarrhea and infectious diarrhea, and thus have the potential to help with Candida infections, as well. For this reason, we provide an overview of therapies prescribed in dermatology that may increase the risk for candidiasis, and we review the literature on whether probiotics are useful in the treatment and prevention of oral and vulvovaginal candidiasis to help dermatologists treating the condition be better informed about their supplemental use with conventional antifungals.

ABSTRACT The pathogenesis of increased stroke risk in human immunodeficiency virus (HIV) remains unclear. Our study investigated the relationship between adventitial and intimal CD3 + T cells and brain arterial remodeling that potentially contributes to HIV-related vasculopathy and stroke. Large brain arteries from 84 HIV + cases and 78 HIV − cases were analyzed to determine interadventitial and luminal diameters, intimal and wall thickness, percent stenosis, and the presence of atherosclerosis. Immunohistochemical analysis was performed to detect and visually score CD3, a pan-T-cell marker, in the intima and adventitia. Our study showed that numbers of adventitial CD3 + T cells are lower among persons with HIV than among those without HIV, especially if CD4 counts are <200, though intimal CD3 + T cell numbers did not differ by HIV status. Among those with HIV but CD4 counts of <200 at the time of death, intimal CD3 + T cells were associated with hypertrophic outward remodeling, while among those with HIV and CD4 of >200 or HIV − controls, intimal CD3 + T cells were associated with hypertrophic inward remodeling. We conclude that intimal lymphocytic inflammation is involved in brain arterial remodeling that may contribute to HIV-related cerebrovascular pathology. IMPORTANCE Although mortality from human immunodeficiency virus (HIV) has decreased with the use of combination antiretroviral therapies, there is now an increased risk of cardiovascular and cerebrovascular disease associated with HIV. Thus, there is a need to understand the pathogenesis of stroke in HIV infection. Our study examines how lymphocytic inflammation in brain arteries may contribute to increased cerebral vasculopathy. With this understanding, our study can potentially help direct future therapies to target and prevent brain arterial remodeling processes associated with HIV.

OBJECTIVE:To test whether HIV is associated with brain large artery vulnerable intima. DESIGN:Cross-sectional study of autopsied HIV-positive (HIV+) cases sex and age-matched to HIV-negative (HIV-) controls. METHODS:Brain large arteries from 302 autopsied cases (50% HIV+) were evaluated morphometrically for the presence of atherosclerosis, size of necrotic core, and fibrous cap thickness. Intima vulnerability was measured as intima elastolytic score [0-5, based on intimal metalloproteinases (MMP)-2, MMP-3, and MMP-9, and tissue inhibitor for MMP-1 and MMP-2 staining], intima inflammatory score (0-3, based on intimal presence of CD3 and CD68 cells and TNF-α staining), neoangiogenesis (factor VIII staining), and apoptosis (caspase 3 staining). Hierarchical generalized linear models were used to obtain the beta estimates and their 95% confidence intervals, adjusting for demographics and vascular risk factors. RESULTS:The prevalence of atherosclerosis did not differ by HIV status. Necrotic cores filled larger proportions of the intima in HIV+ individuals with CD4 cell count above 200 cells/μl at death compared to HIV- controls (adjusted B = 11.6%, P = 0.04). HIV+ individuals had greater elastolytic scores (adjusted B = 0.34, P = 0.02), especially those with less than 200 CD4 cells/μl at death (adjusted B = 0.41, P = 0.01). Intima inflammation, neoangiogenesis, and apoptosis were not different among HIV+ cases versus HIV- controls. CONCLUSION:Individuals with HIV and CD4 cell count at least 200 cells/μl at death had relatively larger necrotic cores, whereas those with HIV and CD4 cell count below 200 cells/μl at death had evidence of increased connective tissue remodeling in the intima. These findings suggest an increased potential for endothelial erosion, thrombosis, and plaque rupture that may relate to higher risk for vascular events.

Introduction: By virtue of their infection, HIV+ patients are subject to chronic inflammation, and show an increased risk for stroke when compared to uninfected controls. We hypothesized that HIV infection would be associated with increased atherosclerotic plaque vulnerability. Methods: Large brain arteries from 162 autopsied individuals (84 with HIV) were stained for metalloproteinase (MMP)-2, MMP-3, MMP-9, Caspase-3, and tumor necrosis factor (TNF)-α, factors reported to increase plaque vulnerability. We measured intensity of staining for each protein in the fibrous cap and scored each as 0 (most intense staining not in cap) or 1 (most intense staining in cap). We then added the ratings from the five stains and created a vulnerability score ranging from 0-5. CD3+ cells (lymphocytes) and CD68+ cells (macrophages) were also rated using semi-quantitative scores. Rating was blind to HIV status. We constructed multilevel models to obtain the β estimates and their 95% confidence intervals (β, 95%CI), adjusting for demographic characteristics, vascular risk factors, and HIV-related immune variables. Results: For the entire sample, the plaque vulnerability score was associated with higher degree of luminal stenosis (0.04, 0.02-0.06) and larger arterial size (0.5 per mm, 0.2-0.8), but not with HIV (-0.65, -2.24-0.95). However, in a subset of individuals with atherosclerosis (n=21), there was a statistical interaction (P<0.04) between HIV and vulnerability score. In a stratified model in HIV+ cases only, a CD4 count of > 200 cells/ul at death was associated with higher vulnerability score (1.42, 0.08-2.76) compared with subjects who remained immunosuppressed. Predictors of vulnerability score among HIV+ subjects included higher CD3 score (1.12, 0.15-2.09), older age (0.18 per year, 0.12-0.25), diabetes (3.00, 1.69-4.24), lower CD4 nadir (-0.01, -0.02to -0.007), antiretroviral use at death (-2.08, -3.84 to -0.32). Conclusions: Plaque vulnerability is positively associated with a higher blood CD4 count, lower CD4 nadir and higher lymphocytic inflammation in brain arteries among HIV+ cases. Investigating the role of HIV-related chronic inflammation and plaque vulnerability may help us better understand the higher risk of stroke among those with HIV.

Background: HIV-infected individuals may display chronic brain inflammation. It is unclear whether this inflammation may play a role in brain arterial pathologies that predispose patients with HIV to stroke. We tested the hypothesis that T cell infiltrates would be associated with brain arterial pathology. Methods: Large brain arteries from 162 patients (84 with HIV) were used in immunohistochemical analysis to detect CD3, a pan T cell marker. A semi-quantitative score of 0 to 3 (absent, mild, moderate, severe) was created by visually rating CD3+ cells within each arterial layer (intima, media, and adventitia). Arterial stenosis, lumen-to-wall ratio and presence of atherosclerosis were measured in each arterial segment of the circle of Willis using previously reported methods of good to excellent reliability. All models were adjusted for co-dependence between arteries of the same subject as well as for age, sex, ethnicity, vascular risks factors, cocaine use and artery type and location. Results: Brain arteries from HIV+ individuals had lower adventitial CD3 scores than HIV- (B = -1.65, p = 0.004). Further stratification demonstrated that the decreased arterial CD3 score was significant only among HIV+ subjects with premortem CD4 counts < 200 cells/μl (B = -2.28, p <0.001). Among HIV+ individuals with premortem CD4 counts ≥ 200 cells/μl, CD3 arterial scores were associated with brain atherosclerosis (B = 0.74, p=0.04). Independent of HIV status, CD3 score was associated with decreased lumen-to-wall ratio (B = -0.37, p = 0.02) and percentage luminal stenosis (B = 1.99, p = 0.004). Among HIV+ cases, higher CD3 score was noted with higher CD4 count at death (per 50, B=0.43, P=0.001), hypertension (B=7.14, P<0.001), male sex (B=6.29, P=<0.001) and prior opportunistic infections (B=3.24, P=0.008) while a lower CD3 score was noted among diabetics (B=-5.36, P<0.001) and reported use of antiretroviral at death (B=-1.39, P=0.01). Conclusions: Among HIV+ individuals with premortem CD4 counts ≥ 200, there exists an association between brain arterial lymphocytic activity with atherosclerosis. These findings may suggest a role for lymphocytic inflammation in HIV-related atherosclerosis in the setting of immune reconstitution.