Review of recent advances in managing periocular skin malignancies.

Management of cutaneous malignancies can be particularly challenging when they are located in the periocular region. The standard of care for localized disease is complete surgical excision, but this may not be possible without significant disruption to visual structures and facial appearance. Definitive radiation may be an option for some patients who cannot or do not wish to undergo surgery. Advances in systemic treatment options for locally advanced and metastatic skin cancers in the past 10 years have prompted investigation into neoadjuvant treatment of periocular cancers. The use of chemotherapy, immune checkpoint inhibitors, and targeted therapies have all been reported with varying degrees of success. For many patients, targeted therapies or immune checkpoint inhibitors should be considered depending on the cancer type, symptoms, and goals with the input of a multidisciplinary cancer care team. In this article, we systematically review the latest updates in surgical, radiotherapeutic, and medical management of periocular malignancies.

Male infertility may be associated with IFT140-related autosomal recessive retinitis pigmentosa.

BACKGROUND: Pathogenic variants in IFT140 have been reported in cases of both syndromic and nonsyndromic retinitis pigmentosa (RP). Syndromic forms of IFT140-related RP have been associated with short-rib thoracic dysplasia. IFT140 variants have also been shown to cause spermatogenic dysfunction leading to infertility. However, variants in IFT140 have not been reported in patients with concurrent RP (including nonsyndromic RP) and infertility. METHODS: A chart review was performed in a 42 year old male with RP and male factor infertility. RESULTS: Genetic testing confirmed this patient's RP was related to variants in IFT140. Chart review and exam confirmed no findings consistent with short-rib thoracic dysplasia, leading to the conclusion that this was a form of nonsyndromic RP as has been previously reported. However, the patient had undergone an infertility workup with findings of spermatogenic dysfunction as found in other males with IFT140-related infertility. This has led us to speculate this patient may have a syndromic form of IFT140 -related RP associated with infertility and abnormal spermatogenesis. CONCLUSIONS: A potential association between IFT140-related RP and male factor infertility may exist.

Alternaria fungal dacryocystitis with cutaneous fistula: a case report.

Alternaria is a fungal genus that can cause opportunistic human infection in immunocompromised hosts. While the majority of clinical manifestations are cutaneous or subcutaneous infections, there are reports of oculomycosis, which is most commonly present as keratomycosis or endophthalmitis.Here, we present a rare case of Alternaria dacryocystitis with cutaneous fistula in a diabetic patient. The patient was referred with a non-healing medial canthal wound and an initial biopsy report showing "ruptured hair follicle;" re-examination of the biopsy specimen with fungal stains led to the diagnosis of alternariosis. The patient underwent surgical debridement and systemic antifungal treatment, with complete resolution of the infection. In order to initiate prompt treatment and prevent invasive disease, fungal infection should be considered in an immunocompromised patient with chronic dacryocystitis and cutaneous fistula or a nonhealing medial canthus wound.

Impact of intrinsic and extrinsic risk factors on early-onset lung disease in cystic fibrosis.

BACKGROUND: Although respiratory pathology is known to develop in young children with cystic fibrosis (CF), the determinants of early-onset lung disease have not been elucidated. OBJECTIVE: We aimed to determine the impact of potential intrinsic and extrinsic risk factors during the first 3 years of life, testing the hypothesis that both contribute significantly to early-onset CF lung disease. DESIGN: We studied 104 infants born during 2012-2017, diagnosed through newborn screening by age 3 months, and evaluated comprehensively to 36 months of age. Lung disease manifestations were quantified with a new scoring system known as CFELD for Cystic Fibrosis Early-onset Lung Disease. The variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene were determined and categorized. Whole genome sequencing was performed on each subject and the data transformed to polygenic risk scores (PRS) that aggregate variants associated with lung function. Extrinsic factors included socioeconomic status (SES) indicators and environmental experiences such as exposures to smoking, pets, and daycare. RESULTS: We found by univariate analysis that CFTR genotype and genetic modifiers aggregated by the PRS method were significantly associated with early-onset CF lung disease. Ordinal logistic regression analysis demonstrated that high and stable SES (maternal education ≥community college, stable 2-parent home, and not receiving Medicaid) and better growth (weight-for-age and height-for-age z-scores) reduced risks, while exposure to smoking and daycare ≥20 h/week increased the risk of CFELD severity. CONCLUSIONS: Extrinsic, modifiable determinants are influential early and potentially as important as the intrinsic risk factors in the onset of CF lung disease.

Ocular Emergencies During the Coronavirus Disease 'Safer at Home Order' in Wisconsin.

INTRODUCTION: The coronavirus pandemic created large shifts in utilization of hospital resources, patient presentations, and delivery of medical care. OBJECTIVES: This retrospective study evaluated the ocular emergencies at a tertiary-care academic hospital in Wisconsin during the COVID-19-related "Safer at Home" order. METHODS: Ophthalmology consultations performed March 23 through May 26, 2020, were compared to the same time period in the 4 preceding years and the subsequent year. Billing codes were obtained to evaluate the diagnoses and procedures performed during this time frame. RESULTS: In 2020, 155 consultations were performed (42 emergency department, 113 inpatient), compared to a mean of 214 over the 5 other study years. The incidence rate ratio (IRR) of total consultations in 2020 was 0.72 (P ≤ 0.001) compared to previous years. Significantly fewer emergency department consultations were performed (IRR 0.62, P ≤ 0.001), while inpatient consultations were similar (IRR 0.88, P = 0.119). The most common diagnosis across all study years was fracture of the skull/orbit with injury to the eye/orbit. In 2020, 13% of consultations led to a procedure, compared to a total of 16% in the other years (IRR 0.59, P = 0.018). CONCLUSIONS: This study demonstrated a 28% reduction in ophthalmology consultations at a major university hospital in Wisconsin during the COVID-19-related "Safer at Home" order, though the number of consultations leading to surgery were stable. This suggests that while patients with less acute needs may have deferred care, those requiring urgent surgery still presented to the emergency department. These data may help hospitals appropriately allocate eye care resources during future public health emergencies.

Defining and identifying early-onset lung disease in cystic fibrosis with cumulative clinical characteristics.

BACKGROUND: Because of the heterogeneity in cystic fibrosis (CF) lung disease among young children, a clinical method to identify early-onset lung disease is needed. OBJECTIVE: To develop a CF early-onset lung disease (CFELD) scoring system by utilizing prospectively collected longitudinal data on manifestations in the first 3 years of life. DESIGN: We studied 145 infants born during 2012-2017, diagnosed through newborn screening by age 3 months, and followed to 36 months of age. Cough severity, pulmonary exacerbations (PEx), respiratory cultures, and hospitalizations were collected at each CF center visit (every 1-2 months in infancy and quarterly thereafter). These data were used to construct the CFELD system and to classify lung disease into five categories: asymptomatic, minimal, mild, moderate, and severe. RESULTS: The most frequent manifestation of CF early lung disease was MD-reported PEx episodes, PEx hospitalizations, and positive Pseudomonas aeruginosa cultures. Parent-reported cough severity was correlated with the number of respiratory hospitalizations (r = 0.48, p < 0.0001). The distribution of CFELD categories was 10% asymptomatic, 17% minimal, 29% mild, 33% moderate, and 12% severe. The moderate and severe categories occurred threefold higher in pancreatic insufficient (PI, 49%) versus sufficient subjects (16%), p < 0.0001. In addition to PI, gastrointestinal and nutrition-related hospitalizations, plasma cytokines interleukin (IL)-6 and IL-10, duration of CFTR modulator therapy, and type of health insurance were significant predictors of CFELD scores. CONCLUSION: The CFELD scoring system is novel, allows systematic evaluation of lung disease prognosis early, and may aid in therapeutic decision-making particularly in the initiation of CFTR modulator therapy.

Altered patterning of trisomy 21 interneuron progenitors.

Individuals with Down syndrome (DS; Ts21), the most common genetic cause of intellectual disability, have smaller brains that reflect fewer neurons at pre- and post-natal stages, implicating impaired neurogenesis during development. Our stereological analysis of adult DS cortex indicates a reduction of calretinin-expressing interneurons. Using Ts21 human induced pluripotent stem cells (iPSCs) and isogenic controls, we find that Ts21 progenitors generate fewer COUP-TFII+ progenitors with reduced proliferation. Single-cell RNA sequencing of Ts21 progenitors confirms the altered specification of progenitor subpopulations and identifies reduced WNT signaling. Activation of WNT signaling partially restores the COUP-TFII+ progenitor population in Ts21, suggesting that altered WNT signaling contributes to the defective development of cortical interneurons in DS.