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Melanoma's rare capacity to undergo heterologous differentiation can create significant diagnostic challenges. The molecular mechanisms underlying this phenomenon are not well understood. We present an unusual case of subungual melanoma exhibiting extensive cartilaginous differentiation and provide insights into its molecular and cytogenomic features. Histopathologically, the tumor was predominantly composed of nodules of malignant cartilage in association with a smaller population of nested epithelioid to rhabdoid cells. Immunohistochemically, the tumor cells in both components were positive for S100, SOX10, and PRAME, and were negative for Melan‐A and HMB‐45. Molecular analysis by whole exome DNA sequence did not detect any pathogenic variants in genes commonly implicated in melanoma. Additional analysis by SNP chromosomal microarray revealed a complex genome characterized by numerous chromosomal losses and gains, including a homozygous deletion of the CDKN2A locus and a heterozygous deletion of the locus containing EXT2, a tumor suppressor implicated in hereditary multiple osteochondromas and secondary chondrosarcomas. This case underscores the importance of recognizing cartilaginous differentiation as a rare manifestation of melanoma, particularly at subungual sites, and suggests that at least some of these melanomas may be driven by non‐canonical molecular pathways. [ABSTRACT FROM AUTHOR]

Background: Racial and ethnic disparities are evident in the accessibility of treatment for opioid use disorder (OUD). Even when medications for OUD (MOUD) are accessible, racially and ethnically minoritized groups have higher attrition rates from treatment. Existing literature has primarily identified the specific racial and ethnic groups affected by these disparities, but has not thoroughly examined interventions to address this gap. Recovery peer navigators (RPNs) have been shown to improve access and overall retention on MOUD. Patients and Methods: In this retrospective cohort study, we evaluate the role of RPNs on patient retention in clinical care at an outpatient program in a racially and ethnically diverse urban community. Charts were reviewed of new patients seen from January 1, 2019 through December 31, 2019. Sociodemographic and clinical visit data, including which providers and services were utilized, were collected, and the primary outcome of interest was continuous retention in care. Bivariate analysis was done to test for statistically significant associations between variables by racial/ethnic group and continuous retention in care using Student's t-test or Pearson's chi-square test. Variables with p value ≤0.10 were included in a multivariable regression model. Results: A total of 131 new patients were included in the study. RPNs improved continuous retention in all-group analysis (27.6% pre-RPN compared to 80.2% post-RPN). Improvements in continuous retention were observed in all racial/ethnic subgroups but were statistically significant in the non-Hispanic Black (NHB) group (p < 0.001). Among NHB, increases in continuous retention were observed post-RPN in patients with male sex (p < 0.001), public health insurance (p < 0.001), additional substance use (p < 0.001), medical comorbidities (p < 0.001), psychiatric comorbidities (p=0.001), and unstable housing (p=0.005). Multivariate logistic regression demonstrated that patients who lacked insurance had lower odds of continuous retention compared to patients with public insurance (aOR = 0.17, 95% CI 0.039-0.70, p=0.015) Conclusions: RPNs can improve clinical retention for patients with OUD, particularly for individuals experiencing several sociodemographic and clinical factors that are typically correlated with discontinuation of care. [ABSTRACT FROM AUTHOR]

Purpose of Review: Polygenic risk scores (PRS) for breast cancer (BC) estimate risk based on the cumulative impact of single-nucleotide polymorphisms. This review outlines current data regarding potential applications of breast cancer PRS. Recent Findings: PRS may have use in unaffected and affected individuals and in those with and without germline pathogenic variants. Incorporation of clinical risk factors strengthens estimates. Multi-ancestry PRS have mitigated but not resolved concerns about applicability across ancestry groups. Summary: PRS represents an important, emerging component of BC risk estimation. Research will help inform optimal utilization and communication, as well as clinical and psychological impact. [ABSTRACT FROM AUTHOR]

Germline genetic evaluation is indicated for all patients with epithelial ovarian cancer (EOC). For testing to have clinical utility, results must be documented within the electronic medical record (EMR) and accessible to providers at the point of care, which can be challenging in the context of current EMR limitations and genetic testing processes. We examined the receipt of genetics services and EMR capture of genetic testing results in patients with EOC. We conducted a retrospective chart review to examine germline genetic evaluations among patients with EOC seen by a gynecologic or medical oncologist at the University of Pennsylvania in 2016. EMRs were reviewed to determine: (1) if patients were referred for genetic evaluation; (2) if genetic testing was performed; (3) if results were documented in office notes, scanned third‐party test reports, and/or the EMR problem list; (4) if provider notes correctly listed the variant classification. Overall, 413 (62%) of patients had documented genetic testing. Genetic testing was documented in almost all provider notes (96%) and the majority of scanned EMR reports (64%). Pathogenic variants were found in 119 (29%) individuals; the majority (70%) had genetic testing documented within EMR problem lists. Provider notes were highly accurate in describing variant classification. In this study, genetic testing was performed and documented in the EMR for most EOC patients. Approximately one‐third of those tested did not have scanned test reports specifying variant found, limiting the utility of test results for cascade testing and therapeutic decisions. [ABSTRACT FROM AUTHOR]

Purpose: To assess and analyze the visual outcomes of patients with retinal vein occlusions in a real-world setting with a long-term follow-up of more than 5 years.Methods: Retrospective analysis of 56 patients having retinal vein occlusions from a tertiary eye center, with a mean follow-up of 7 years was performed. Primary outcome measures were mean change in best-corrected visual acuity (BCVA) from baseline at 6 months, 1 year, 2 years, 3 years, and final visit (≥5 years), proportion of patients having BCVA better than 20/40 and worse than 20/200, and mean number of injections. Secondary outcome measures were change in central macular thickness (CMT), development of subsequent retinal vein occlusion (RVO) in same eye or the other eye, and development of neovascular complications.Results: The mean change in letter score was + 11.84 in branch RVO (BRVO), +7.14 in non-ischemic central RVO (CRVO), and -9.5 in ischemic CRVO at 1 year, which changed to + 8.57, -5 and - 24, respectively, at the end of follow-up. CMT had improved from 506 ± 98.8 μm, 576.44 ± 149 μm, and 618 ± 178.27 μm, respectively, at baseline to 267 ± 94 μm, 345.20 ± 122.61 μm, and 265.50 ± 107.75 μm, respectively, in BRVO, non-ischemic, and ischemic hemi RVO (HRVO)/CRVO groups. The total mean number of injections given in BRVO, non-ischemic CRVO, and ischemic CRVO groups were 4.6, 6.6, and 4.1, respectively. None of the patients with BRVO developed neovascular glaucoma (NVG). Non-ischemic to ischemic HRVO/CRVO conversion was noted in 4/11 eyes at a mean duration of 12.6 months. NVG was noted in 7/9 eyes (77.8%) in initial ischemic CRVO/HRVO group and 3/4 (75%) converted eyes.Conclusion: Patients with BRVO have good visual outcomes with anti-VEGF, while in CRVO results may vary considerably owing to patient compliance and treatment burden on long-term follow-up in a real-world setting. [ABSTRACT FROM AUTHOR]

The analytical validation is reported for a targeted methylation-based cell-free DNA multi-cancer early detection test designed to detect cancer and predict the cancer signal origin (tissue of origin). A machine-learning classifier was used to analyze the methylation patterns of >105 genomic targets covering >1 million methylation sites. Analytical sensitivity (limit of detection [95% probability]) was characterized with respect to tumor content by expected variant allele frequency and was determined to be 0.07%-0.17% across five tumor cases and 0.51% for the lymphoid neoplasm case. Test specificity was 99.3% (95% confidence interval, 98.6–99.7%). In the reproducibility and repeatability study, results were consistent in 31/34 (91.2%) pairs with cancer and 17/17 (100%) pairs without cancer; between runs, results were concordant for 129/133 (97.0%) cancer and 37/37 (100%) non-cancer sample pairs. Across 3- to 100-ng input levels of cell-free DNA, cancer was detected in 157/182 (86.3%) cancer samples but not in any of the 62 non-cancer samples. In input titration tests, cancer signal origin was correctly predicted in all tumor samples detected as cancer. No cross-contamination events were observed. No potential interferent (hemoglobin, bilirubin, triglycerides, genomic DNA) affected performance. The results of this analytical validation study support continued clinical development of a targeted methylation cell-free DNA multi-cancer early detection test. [ABSTRACT FROM AUTHOR]

A one and half-year-old baby boy presented with subacute regression of milestones in all domains. On examination, he had spastic dystonic quadriparesis. Reflexes were brisk. Magnetic resonance imaging of the brain showed diffuse cavitating leukodystrophy involving bilateral periventricular white matter, centrum semiovale, and corona radiata. Magnetic resonance spectroscopy revealed a lactate peak and serum lactate levels were also elevated. Genetic studies revealed compound heterozygous autosomal recessive mutations in IBA57 gene. This case illustrates a rare mitochondrial encephalopathy called multiple mitochondrial dysfunction syndrome-3 caused by a novel IBA57 gene mutation. [ABSTRACT FROM AUTHOR]

Germ cell tumors are rare tumors and may pose a diagnostic dilemma. We present a 15-year-old boy with insidious onset right hemiparesis followed by polyuria and polydipsia. Later, he also developed cognitive decline and speech disturbances. Serial magnetic resonance images (MRIs) over a 2-year period showed progressive atrophy of the left caudate nucleus, along with Wallerian degeneration of the left internal capsule and crus of midbrain. Further in the course, imaging revealed an ill-defined signal intensity involving left ganglio-capsulo-thalamic region with increased perfusion which was suggestive of basal ganglia germinoma. Beta human chorionic gonadotropin levels were mildly elevated. This case illustrates an uncommon presentation of a central nervous system germinoma which is often misdiagnosed in the early stages because of its atypical symptomatology and MRI findings. [ABSTRACT FROM AUTHOR]

Introduction: Cyclin-dependent-kinase 4/6(CDK4/6) inhibitors are widely used as a first-line systemic treatment for patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer. Although many patients with metastatic breast cancer require palliative radiotherapy (RT), there are limited data on the safety of combining a CDK4/6 inhibitor with palliative RT. Case Report: Presented is a case of acute high-grade radiation dermatitis with low-dose palliative RT following administration of palbociclib. A 49-year-old woman with newly diagnosed hormone receptor-positive invasive ductal carcinoma of the left breast presented with lytic bone lesions in the left femur and lumbar spine. The patient initiated treatment with goserelin, tamoxifen, and palbociclib. She underwent prophylactic surgical fixation of the left femur and received post-operative RT encompassing the entire surgical nail (30 Gy/10 fractions) and palliative RT to the lumbar spine for pain relief (20 Gy/5 fractions). During cycle 4, palbociclib was stopped 3 days prior to the start of RT to reduce the risk of toxicity risk. However, 16 days after starting RT, she developed painful erythematous papules and bullae with moist desquamation on the left groin and lumbar spine. Management & Outcome: Her symptoms were managed with topical Aquaphor-lidocaine, silver sulfadiazine, and aluminum acetate soaks. Dermatitis subsided to dry desquamation within 2 weeks. The patient denied late toxicity at 11 months follow-up. Discussion: Larger retrospective or prospective studies are needed to further elucidate the safety of combined CDK4/6 inhibitors and RT. In the meantime, special precautions are warranted in patients receiving combined therapy. [ABSTRACT FROM AUTHOR]

(E-H) Pancreatic sections were analysed for (E) -cell mass (F) apoptosis by double staining for TUNEL and insulin (10,000 -cells/mouse, n = 6 mice/group) and (G) islet vessel area quantified by CD31/ Insulin co-staining (100 islets/mouse, n = 6 mice/group). Graph: Fig 3 Ang-2 over-expression impairs islet function but protects from cytokine treatmentin isolated islets. The Fig 4D results are consistent when comparing results of the t-test to the Wilcoxon test, except for comparing Ang2-rtTA HFD to Ant2-rtTA ND for which the Wilcoxon test indicated nonsignificant differences (p = 0.20). [Extracted from the article]

Purpose: Coats' disease is associated with poor outcomes, and there are limited studies on long-term outcomes of Coats' disease. The purpose of our study is to identify various predictive factors to help in prognosticating the treatment outcomes in advanced Coats' disease in children.Methods: This is a retrospective case series from a single tertiary eye care center of children (<18 years) diagnosed with coat's disease. Sixty-seven patients with Coat's disease were identified from the medical records from 2009 to 2020. Patients' demographic data, clinical presentation, stage, extent of involvement, detailed treatment history, clinical sequelae post-treatment (including complications and anatomical and functional outcomes) were noted. Binary logistic regression was performed to correlate the predictive factors for anatomical and functional improvement.Results: Of the 67 patients, 51 eyes of 51 patients were included in the study. The male to female proportion was 2.2. Mean age at presentation was 4.98 ± 3.55 years (range: 2 months-15 years). Mean duration of follow-up was 31.53 ± 26.38 months. Overall, our globe salvage rate was 92.2%. We found that vitreoretinal fibrosis (P < 0.001), subretinal gliosis (P < 0.001), vitreous hemorrhage (P = 0.02), tractional or combined retinal detachment (P < 0.001), foveal scar (P < 0.006), and cataract (P < 0.001) to be important factors to affect the outcome.Conclusion: Advanced stage of presentation (stage 3B and above), diffuse involvement, cataract, vitreoretinal fibrosis (preretinal and subretinal), vitreous hemorrhage, tractional or combined retinal detachment, and anterior hyaloid proliferation are poor prognostic factors for globe salvage in advanced disease. Subretinal gliotic nodule or scar and lack of visual rehabilitation suggest poor functional outcomes. [ABSTRACT FROM AUTHOR]

The article discusses effectiveness of treatment of human immunodeficiency virus (HIV) with pre-exposure prophylaxis (PrEP). It mentions that Sexually transmitted infections (STIs) often reflected on skin and are treated by dermatologist, discussed on the effect of Pre-exposure prophylaxis (PrEP) which uses antiretrovirals to prevent transmission and infection with HIV; and that PrEP with emtricitabine plus tenofovir disoproxil fumarate was approved by the US Food and Drug Administration (FDA).

Methotrexate is historically recognized as an effective treatment of pemphigus but its utility as a single or alternate steroid‐sparing agent was not recognized in recent consensus recommendations in pemphigus management. We aimed to evaluate the efficacy and safety of a treatment course for pemphigus that involves methotrexate as a single or steroid‐sparing agent. In a retrospective cohort study, we examined patients with pemphigus vulgaris or pemphigus foliaceus who were on ≥3 months of methotrexate therapy. Efficacy and safety were evaluated by established pemphigus disease endpoints. Of the 34 patients who met inclusion criteria, 25 (73.5%) were on glucocorticoids at time of methotrexate initiation (median follow‐up: 5.4 years; median time on methotrexate: 3.7 years). An appreciable proportion achieved disease control (91.2%), with some achieving clinical remission off all systemic therapies (23.5%). For patients on glucocorticoids, median time to control was 42 days, median time to minimal steroid dose tapering (5 mg prednisone) was 161 days, and median time to complete steroid tapering was 308 days. For patients on methotrexate as a single agent, median time to control was 119 days. Among all patients, relapse commonly occurred (88.2%). At last follow‐up, 26.5% were managed on topical therapies alone and 11.8% required systemic steroid therapy. Methotrexate was largely tolerated with a low incidence of adverse events leading to treatment discontinuation (2.9%). Methotrexate has the potential to be an effective and well‐tolerated option for patients and may be considered for use as an alternate single or steroid‐sparing agent for pemphigus. [ABSTRACT FROM AUTHOR]

This study aimed to describe nurses' experiences with personal protective equipment while providing patient care during the first wave of the COVID-19 pandemic in the US. From May 2020 to September 2020, 100 individual interviews were conducted with nurses from diverse backgrounds and practice settings. Interviews were audio-recorded, transcribed, and verified for thematic analysis. Three key themes emerged related to personal protective equipment during COVID-19: (1) concerns with safety, (2) concerns with personal protective equipment supply, and (3) concerns with health care systems changing personal protective equipment policies. These findings support the importance of transparent and equitable institution-wide PPE standards in creating safe working environments. Clear communication around personal protective equipment policies and procedures, personal protective equipment education, and assurance of equitable access to equipment that can mitigate risk and disability while also reducing fear, confusion, and frustration among nurses. Maintaining clear and consistent personal protective equipment guidelines and communication regarding supplies and procedures enhances transparency during both routine and critical times de-escalating the inevitable strain concomitant with providing patient care during a global pandemic. [ABSTRACT FROM AUTHOR]

This study situates transnégritude within discussions that consider the ways in which young people in Senegal, with a shared transcolonial narrative, bound through an 'imagined community,' negotiate their space, their identities, and their ways of knowing through a Hip-Hop pedagogy. Our analysis is informed by Mignolo's epistemic disobedience and the geo- and body-politics that challenge neo-colonial epistemologies. The global scope of Hip-Hop culture and its manifestations in West Africa nuances the ways in which young people view education and its impact on their social identity. A transnégritude perspective aptly 'straddles' black identity, agency, and deconstructionism and allows for a fluid navigation of Hip-Hop pedagogy. Through a Hip-Hop pedagogy, young people in Senegal work towards social transformation vis-a-vis informal education as a response to imperialism. In so doing, this study intends to contribute to qualitative inquiries on the connections between Hip-Hop, identity formation, and the 'fluidity and location of engagement' in Hip-Hop culture. The goal is to challenge the formal schooling context and interrogate youth identity and engagement vis-a-vis social transformation. [ABSTRACT FROM AUTHOR]

Of note, chlamydia and gonorrhea are now some of the most common STIs, even though dermatologists less frequently screen for these infections.[4] Of the 81 providers, 54% report always or sometimes taking a sexual history, while 46% rarely or never take a sexual history. Dear Editor, The field of dermatology has historical roots in the diagnosis and treatment of sexually transmitted infections (STIs). The results of dermatologist demographics, STIs observed in practice, and STI clinical practice patterns are shown in Tables 1 and 2. [Extracted from the article]

Purpose: A deep learning system (DLS) using artificial intelligence (AI) is emerging as a very promising technology in the future of healthcare diagnostics. While the concept of telehealth is emerging in every field of medicine, AI assistance in diagnosis can become a great tool for successful screening in telemedicine and teleophthalmology. The aim of our study was to assess the acceptability of AI-based retina screening.Methods: This was a prospective non-randomized study performed in the outpatient department of a tertiary eye care hospital. Patients older than 18 years who came for a regular eye check-up or a routine retina screening were recruited in the study. Fundus images of the posterior pole were captured on fundus on a phone camera (REMIDIOTM, India) with a built-in AI software (Netra.AI) that can identify normal versus abnormal retina. The patients were then given an 8-point questionnaire to assess their acceptance and willingness toward AI-based screening. We recruited 104 participants.Results: We found that 90.4% were willing for an AI-based fundus screening; 96.2% were satisfied with AI-based screening. Patients with diabetes (P = 0.03) and the male population (P = 0.029) were more satisfied with the AI-based screening. The majority (i.e., 97.1%) felt that AI-based screening gave them a better understanding of their eye condition and 37.5% felt that AI-based retina screening prior to a doctor's visit can help in routine screening.Conclusion: Considering the current COVID-19 pandemic situation across the globe, this study highlights the importance of AI-based telescreening and positive patient approach toward this technology. [ABSTRACT FROM AUTHOR]

We aim to describe ocular infection epidemiology for a public tertiary care hospital in New York City (NYC). We retrospectively reviewed 558 patients with ocular isolates from conjunctival, corneal, and intraocular culture from 2009 to 2017 for microbial growth and antimicrobial sensitivities. In total, 185 ocular cultures (33%) had growth and the most commonly isolated microbes overall were Staphylococcus aureus (S. aureus) (23%), coagulase-negative Staphylococcus (CoNS) (23%), Pseudomonas aeruginosa (P. aeruginosa) (16%), and Streptococcus viridans (S. viridans) group (11%). The most common microbes within corneal (n = 61), conjunctival (n = 34), and intraocular isolates (n = 9) were P. aeruginosa (37.7%), S. aureus (35.3%), and S. viridans group (33.3%), respectively. Proportion of isolates exhibiting multi-drug resistance decreased over time (P =.006). The microbial epidemiology of ocular infection of a public NYC hospital was distinct from other geographic locations, underscoring the importance of examining local profiles to more precisely inform empiric therapy. [ABSTRACT FROM AUTHOR]

Low forced vital capacity (FVC) is associated with decreased exercise capacity in CHD. Multiple prior cardiac surgeries have been associated with low FVC. We seek to understand the relationship between low FVC, number of cardiac surgeries and cardiopulmonary response leading to decreased exercise capacity. Retrospective chart review of demographics, surgical history and exercise testing including spirometry was performed in patients with CHD. Single ventricle patients were excluded. Low FVC was defined as a Z-score below the lower limit of normal. Exercise parameters were expressed as a percent of predicted. There were 93 patients with 2 ventricle CHD identified over 34 months with cardiopulmonary exercise testing. The FVC Z-score directly correlated with peak V̇O2% (R2 = 0.07, p < 0.05), and the O2 pulse% (R2 = 0.25, p < 0.0001). The VE/VCO2 was inversely related to the FVC Z-score (R2 = 0.11, p < 0.01). Patients with minimum three prior surgeries had decreased peak VO2% (63.7 vs. 72.8, p < 0.05), decreased peak O2 pulse% (80.8 vs. 97.9, p < 0.01) and a lower mean FVC Z-score (− 1.9 vs − 0.38, p < 0.01). The FVC Z-score and number of surgeries both predicted peak V̇O2% in multivariate analysis. Our study demonstrated that low FVC and three or more prior cardiac surgeries were associated with lower exercise capacity and lower stroke volume response. More cardiac surgeries were also associated with low FVC. However, both low FVC and the number of surgeries were independent predictors of exercise capacity. [ABSTRACT FROM AUTHOR]

Recent advances in systematic conservation planning make use of modern portfolio theory (MPT)—a framework to construct and select optimal allocation of assets—to address the challenges posed by climate change uncertainty. However, these methods are difficult to implement for fine‐scale conservation planning when the information on future climate scenarios is insufficient. Insufficient information makes the estimators of the key inputs in the optimisation procedure unreliable leading to technical problems for the construction of optimal asset allocation.We identify three statistical methods—constant correlation model, the Ledoit–Wolf approach and the weighted non‐negative least‐squares approach—that can overcome the lack of sufficient information and enable the use of MPT for fine‐scale conservation planning.We illustrate the use of the three methods for identifying efficient portfolio allocation strategies, that is, strategies that give minimum amount of risk for a chosen level of return or maximum return for a chosen level of risk, using case studies of wetland conservation planning in North America and coastal conservation planning in Australia. We compare conservation planning strategies with complete information using standard portfolio theory and with insufficient information using the three methods to highlight their advantages and disadvantages. We find the Ledoit–Wolf and weighted non‐negative least‐squares approaches perform well and can identify risk‐return outcomes that are close to those identified with complete information.The methods presented in this study broaden the range of cases where the application of MPT is possible in conservation planning to enhance its uptake and lead to more efficient allocation of conservation resources. [ABSTRACT FROM AUTHOR]

Recent studies have shown that individuals with sickle cell disease (SCD) exhibit greater vasoconstriction responses to physical autonomic stressors, such as heat pain and cold pain than normal individuals, but this is not the case for mental stress (MTS). We sought to determine whether this anomalous finding for MTS is related to inter-group differences in baseline cardiac and vascular autonomic function. Fifteen subjects with SCD and 15 healthy volunteers participated in three MTS tasks: N-back, Stroop, and pain anticipation (PA). R–R interval (RRI), arterial blood pressure and finger photoplethysmogram (PPG) were continuously monitored before and during these MTS tasks. The magnitude of vasoconstriction was quantified using change in PPG amplitude (PPGa) from the baseline period. To represent basal autonomic function, we assessed both cardiac and vascular arms of the baroreflex during the baseline period. Cardiac baroreflex sensitivity (BRSc) was estimated by applying both the "sequence" and "spectral" techniques to beat-to-beat measurements of systolic blood pressure and RRIs. The vascular baroreflex sensitivity (BRSv) was quantified using the same approaches, modified for application to beat-to-beat diastolic blood pressure and PPGa measurements. Baseline BRSc was not different between SCD and non-SCD subjects, was not correlated with BRSv, and was not associated with the vasoconstriction responses to MTS tasks. BRSv in both groups was correlated with mean PPGa, and since both baseline PPGa and BRSv were lower in SCD, these results suggested that the SCD subjects were in a basal state of higher sympathetically mediated vascular tone. In both groups, baseline BRSv was positively correlated with the vasoconstriction responses to N-back, Stroop, and PA. After adjusting for differences in BRSv within and between groups, we found no difference in the vasoconstriction responses to all three mental tasks between SCD and non-SCD subjects. The implications of these findings are significant in subjects with SCD since vasoconstriction reduces microvascular flow and prolongs capillary transit time, increasing the likelihood for vaso-occlusive crisis (VOC) to be triggered by exposure to stressful events. [ABSTRACT FROM AUTHOR]

Purpose: Intravitreal anti-vascular endothelial growth factor (VEGF) injection therapy has emerged as the mainstay of treatment in the management of diabetic macular edema (DME) today. Various systemic risk factors have to be considered before initiating anti-VEGF therapy. The aim of our study was to form a consensus on various systemic factors to consider before starting anti-VEGF therapy for DME. Methods: A questionnaire was created and sent across to various retina specialists across India. A GoogleTM form with various questions pertaining to what systemic parameters would one consider before giving anti-VEGF therapy for DME was sent to each of them by email/WhatsAppTM/direct telephonic interview. Results: Of the 650 retina specialists contacted, 322 responded to the questionnaire. There was no difference in responses between private and institutional practitioners. The majority would consider RBS (85%), HbA1c (61%), blood pressure (63%), and renal function (57%) as a routine before administering the anti-VEGF injection, while the majority would not consider hemoglobin (63%) or lipid profile (55%) of the patient as a routine practice prior to administering the injection. Conclusion: In our study, most VR specialists prefer to consider RBS, HbA1c, BP, and renal profile (creatinine) routinely prior to anti-VEGF injection. We suggest that it is important to consider blood pressure control, glycemic control, HbA1c, Hb, lipid profile, and renal profile (UACR, eGFR, and creatinine) prior to anti-VEGF therapy in all diabetic patients and to discuss the need for statins in patients with dyslipidemias with the physician. [ABSTRACT FROM AUTHOR]

Purpose: Amblyopia is a significant public health problem. Photoscreeners have been shown to have significant potential for screening; however, most are limited by cost and display low accuracy. The purpose of this study was validate a novel artificial intelligence (AI) and machine learning-based facial photoscreener "Kanna," and to determine its effectiveness in detecting amblyopia risk factors.Methods: A prospective study that included 654 patients aged below 18 years was conducted in our outpatient clinic. Using an android smartphone, three images of each the participants' face were captured by trained optometrists in dark and ambient light conditions and uploaded onto Kanna. Deep learning was used to create an amblyopia risk score based on our previous study. The algorithm generates a risk dashboard consisting of six values: five normalized risk scores for ptosis, strabismus, hyperopia, myopia and media opacities; and one binary value denoting if a child is "at-risk" or "not at-risk." The presence of amblyopia risk factors (ARF) as determined on the ophthalmic examination was compared with the Kanna photoscreener.Results: Correlated patient data for 654 participants were analyzed. The mean age of the study population was 7.87 years. The algorithm had an F-score, 85.9%; accuracy, 90.8%; sensitivity, 83.6%; specificity, 94.5%; positive predictive value, 88.4%; and negative predictive value, 91.9% in identifying amblyopia risk factors. The P value for the amblyopia risk calculation was 8.5 × 10-142 implying strong statistical significance.Conclusion: The Kanna photo-based screener that uses deep learning to analyze photographs is an effective alternative for screening children for amblyopia risk factors. [ABSTRACT FROM AUTHOR]

Smartphone-based fundus imaging (SBFI) is a low-cost approach for screening of various ophthalmic diseases and particularly suited to resource limited settings. Thus, we assessed how best to upskill alternative healthcare cadres in SBFI and whether quality of obtained images is comparable to ophthalmologists. Ophthalmic assistants and ophthalmologists received a standardized training to SBFI (Heine iC2 combined with an iPhone 6) and 10 training examinations for capturing central retinal images. Examination time, total number of images, image alignment, usable field-of-view, and image quality (sharpness/focus, reflex artifacts, contrast/illumination) were analyzed. Thirty examiners (14 ophthalmic assistants and 16 ophthalmologists) and 14 volunteer test subjects were included. Mean examination time (1st and 10th training, respectively: 2.17 ± 1.54 and 0.56 ± 0.51 min, p <.0001), usable field-of-view (92 ± 16% and 98 ± 6.0%, p =.003) and image quality in terms of sharpness/focus (p =.002) improved by the training. Examination time was significantly shorter for ophthalmologists compared to ophthalmic assistants (10th training: 0.35 ± 0.21 and 0.79 ± 0.65 min, p =.011), but there was no significant difference in usable field-of-view and image quality. This study demonstrates the high learnability of SBFI with a relatively short training and mostly comparable results across healthcare cadres. The results will aid implementing and planning further SBFI field studies. [ABSTRACT FROM AUTHOR]

The landscape of genetic testing for breast cancer susceptibility has transformed dramatically over the last decade and a half. Traditionally, the process of genetic testing resided fully within a medical infrastructure, from identification of appropriate testing candidates to gene selection to risk mitigation recommendations. More recently, decreasing costs, advancing technology, and a growing understanding of therapeutic implications of certain genetic test results have led to more widespread uptake of testing that increasingly involves broad multigene panels. Germline genetic testing for breast cancer susceptibility can now be obtained through one of three approaches: through clinical care; a direct‐to‐consumer (DTC) approach that is entirely consumer‐driven; or a hybrid, patient‐initiated, provider‐mediated model. Increased access to testing has led to extensive dialogue about the best way to conduct testing and act on results. Points of discussion include: selection of appropriate candidates for genetic testing; optimal composition of genes on panels; informed consent; safe return of results; privacy; and legal protections for those found to have relevant pathogenic or likely pathogenic variants. As more individuals undergo genetic testing, a growing population of individuals with inherited breast cancer predisposition informs optimal management of cancer risk and also highlights unanswered questions. This article aims to review the current state of genetic testing for inherited breast cancer susceptibility including testing approaches, the legal, ethical and social landscape, and selected contemporary management issues. [ABSTRACT FROM AUTHOR]

Purpose: Women with Li-Fraumeni syndrome (LFS), a cancer predisposition syndrome caused by germline mutations in TP53, have an over 50% risk of developing breast cancer by age 70. Patients with LFS are at risk for radiation-induced malignancies; however, only small case series have prior investigated radiation risks in the treatment of breast cancer. We therefore aimed to investigate the risk of malignancy in breast cancer patients with LFS following adjuvant radiotherapy. Methods: A single-institution retrospective chart review was conducted for female breast cancer patients with confirmed germline TP53 mutation. The frequency of radiation-induced malignancies in LFS patients was compared to non-LFS breast cancer cases reported in the Penn Medicine Cancer Registry via statistical analyses. Results: We identified 51 female LFS breast cancer patients with 74 primary diagnoses. Fifty-seven% had a history of breast cancer only, and 25% had breast cancer as their presenting diagnosis of LFS. LFS-associated breast cancers were predominantly invasive ductal carcinoma (48%) and HER2+ (58%). Twenty patients underwent adjuvant radiotherapy with a median follow-up of 12.5 (2–20) years. Of 18 patients who received radiation in a curative setting, one (6%) patient developed thyroid cancer, and one (6%) patient developed sarcoma in the radiation field. This risk for radiation-induced malignancy associated with LFS was higher for both sarcoma and thyroid cancer in comparison with the control cohort. Conclusions: We found a lower risk of radiation-induced secondary malignancies in LFS breast cancer patients than previously reported in the literature (33% risk of radiation-induced sarcoma). These findings suggest that LFS may not be an absolute contraindication for radiotherapy in breast cancer. The potential risk for locoregional recurrence without radiotherapy must be weighed against the long-term risk for radiation-induced malignancies in consideration of adjuvant radiotherapy for LFS breast cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Deep learning is a newer and advanced subfield in artificial intelligence (AI). The aim of our study is to validate a machine-based algorithm developed based on deep convolutional neural networks as a tool for screening to detect referable diabetic retinopathy (DR).Methods: An AI algorithm to detect DR was validated at our hospital using an internal dataset consisting of 1,533 macula-centered fundus images collected retrospectively and an external validation set using Methods to Evaluate Segmentation and Indexing Techniques in the field of Retinal Ophthalmology (MESSIDOR) dataset. Images were graded by two retina specialists as any DR, prompt referral (moderate nonproliferative diabetic retinopathy (NPDR) or above or presence of macular edema) and sight-threatening DR/STDR (severe NPDR or above) and compared with AI results. Sensitivity, specificity, and area under curve (AUC) for both internal and external validation sets for any DR detection, prompt referral, and STDR were calculated. Interobserver agreement using kappa value was calculated for both the sets and two out of three agreements for DR grading was considered as ground truth to compare with AI results.Results: In the internal validation set, the overall sensitivity and specificity was 99.7% and 98.5% for Any DR detection and 98.9% and 94.84%for Prompt referral respectively. The AUC was 0.991 and 0.969 for any DR detection and prompt referral respectively. The agreement between two observers was 99.5% and 99.2% for any DR detection and prompt referral with a kappa value of 0.94 and 0.96, respectively. In the external validation set (MESSIDOR 1), the overall sensitivity and specificity was 90.4% and 91.0% for any DR detection and 94.7% and 97.4% for prompt referral, respectively. The AUC was. 907 and. 960 for any DR detection and prompt referral, respectively. The agreement between two observers was 98.5% and 97.8% for any DR detection and prompt referral with a kappa value of 0.971 and 0.980, respectively.Conclusion: With increasing diabetic population and growing demand supply gap in trained resources, AI is the future for early identification of DR and reducing blindness. This can revolutionize telescreening in ophthalmology, especially where people do not have access to specialized health care. [ABSTRACT FROM AUTHOR]

Scholars and students of comparative education routinely, and often reflexively, categorize places with labels that have complex and problematic histories, connotations and associations. Both comparative education classrooms and scholarship will benefit from reflecting on the dynamics of labeling places. We seek to provide a framework for analyzing the main issues and risks associated with labeling with a heuristic we call the 3P framework. It invites students and scholars to consider the ways in which power, perspective, and plurality are expressed through the terms we apply to places. Through this framework, we identify common pitfalls in labeling. We provide a table with open access resources that critically examine many of the most important and common geographic labels in our field. To illustrate how these issues are manifested in particular contexts, we provide two vignettes, on South Asia and Estonia. The vignettes show how issues of power, perspective and plurality are manifested through the labels used and applied in specific places where we conduct research. Finally, we examine how the labeling process is situated in specific contexts and how meaning is culturally rooted; in doing so, we explain how the exclusive use of English-language labels in this piece is necessarily incomplete. The piece concludes with recommendations for teaching with this framework and for producing comparative education scholarship that deploys labels with greater reflexivity and intentionality. [ABSTRACT FROM AUTHOR]

The article describes the case of a 57-year-old man with a history of hypertension and who presented with 10 days of blue skin discoloration on the bilateral arms and trunk, without any associated pain or itch. Drugs being taken by the patient include hydrochlorothiazide, olmesartan, and amlodipine. The patient was diagnosed of having infectious pseudochromhidrosis from Bacillus cereus. Other differential diagnosis for blue skin discoloration include hypoxenia and sweat pigmentation.

PURPOSE: Tumor-only genomic profiling (TGP) is increasingly advocated for all patients with cancer given the possible therapeutic implications. It is critical to develop clinical algorithms to identify and address potentially actionable germline findings identified by TGP. METHODS: A multidisciplinary team analyzed publicly available data for genes in which mutations are implicated in germline cancer susceptibility and established a pipeline to automate clinical referral for evaluation of TGP findings. RESULTS: A total of 2,308 patients underwent TGP, with 81 patients (3.5%) identified by the automatic referral pipeline; 37 patients (1.6%) were referred outside the pipeline based on concerns by the molecular geneticist, pathologist, or oncologist regarding genotype-phenotype correlation. Thirty-one patients (38%) and 17 patients (46%) underwent germline testing from the automatic pipeline and other referrals, respectively, and of these patients, 23 (72%) and four (24%) had confirmed germline pathogenic variants (GPVs), respectively. The majority of confirmed GPVs were in automatic referral genes, with BRCA2 being most common (confirmed GPVs in 11 [85%] of 13 patients tested), followed by PALB2 (five [67%] of six patients), BRCA1 (two [40%] of five patients), MSH6 (two of three patients), and MLH1 (two of two patients). Forty-eight percent of confirmed GPVs were found in tumors known to be associated with germline mutations in the gene. Germline testing was not performed in 50 (62%) of 81 patients identified by automatic referral as a result of poor patient health or death (30%), lack of follow-up (30%), and patient refusal (30%). CONCLUSION: Of patients undergoing TGP, 5% had somatic findings triggering referral, and implementation of an automatic referral pipeline based solely on gene versus other clinical or molecular features resulted in a 74% germline confirmation. However, only 41% of referred patients underwent germline testing. Systems-based approaches are needed to identify carriers of actionable germline cancer susceptibility mutations identified by TGP. [ABSTRACT FROM AUTHOR]

Background: Breast cancer therapies are associated with a risk of cardiac dysfunction, most commonly defined by changes in left ventricular ejection fraction (LVEF). Recently, the authors identified 3 classes of LVEF change after exposure to anthracyclines and/or trastuzumab using latent class growth modeling. The objective of the current study was to characterize the clinical, biochemical, and functional profiles associated with LVEF trajectory class membership. Methods: Transthoracic echocardiography and biomarker assessments were performed and questionnaires were administered at standardized intervals in a longitudinal cohort of 314 patients with breast cancer who were treated with anthracyclines and/or trastuzumab. Univariable and multivariable multinomial regression analyses evaluated associations between baseline variables and LVEF trajectory class membership. Generalized estimating equations were used to define mean changes in cardiovascular measures over time within each class. Results: Among the 3 distinct subgroups of LVEF changes identified (stable [class 1]; modest, persistent decline [class 2]; and significant early decline followed by partial recovery [class 3]), higher baseline LVEF, radiotherapy, and sequential therapy with anthracyclines and/or trastuzumab were associated with class 2 or 3 membership. Sustained abnormalities in longitudinal strain and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) were observed in patients in class 2, as were heart failure symptoms. Similar abnormalities were observed in patients in class 3, but there was a trend toward recovery, particularly for longitudinal strain. Conclusions: Patients with modest, persistent LVEF declines experienced sustained abnormalities in imaging and biochemical markers of cardiac function and heart failure symptoms. Further investigation is needed to characterize the long‐term risk of heart failure, particularly in those with modest LVEF declines. Modest declines in left ventricular ejection fraction (LVEF) in patients with breast cancer who are treated with cardiotoxic cancer therapy are accompanied by an increased incidence of biochemical and functional abnormalities. This suggests that declines in LVEF that do not reach the conventional thresholds used for the diagnosis of cardiotoxicity could be more clinically important than previously understood. [ABSTRACT FROM AUTHOR]