Quality of life analysis in patients with retinitis pigmentosa.

INTRODUCTION: Retinitis pigmentosa (RP) is a chronic progressive disease causing loss of visual acuity and ultimately blindness. This visual impairment can contribute to psychiatric comorbidity and worse overall quality of life (QOL). Our goal was to assess the relationship between the severity of disease for people with RP and QOL as it pertains to mental health, social support, disability resources, and financial factors. METHODS: This was a survey study conducted from June 2021 to February 2022 including 38 people with RP. Quality of life was assessed through a survey questionnaire focusing specifically on demographics, visual function, family, employment, social support, and mental health/well-being. Statistical analysis was conducted using a Chi-squared test for significance. RESULTS: A best-corrected visual acuity (BCVA) of less than 20/200 (p= 0.0285) and living alone (p=0.0358) were both statistically significant independent risk factors for experiencing depressive symptoms. Highest education level attained and unemployment rate were not found to be related to the development of depressive symptoms. Subjects had a higher unemployment rate (64% vs. US rate of 3.6%) and a high likelihood of reporting depressive symptoms (47.4%). CONCLUSIONS: People with RP are more likely to be unemployed and to develop depressive symptoms when compared to the general population. Similar to previous studies' findings, those with a BCVA of less than 20/200 were statistically more likely to experience depressive symptoms; living alone is a novel risk factor that is also associated with the presence of depressive symptoms. Contrary to prior findings, highest education level and unemployment status were found not to be related to the development of depressive symptoms. These patients may benefit from regular depression screenings and optional establishment of care with a psychiatrist or psychologist if they live alone or their BCVA is 20/200 or worse.

Phase II, Single-Arm Trial of Induction and Concurrent Vismodegib With Curative-Intent Radiation Therapy for Locally Advanced, Unresectable Basal Cell Carcinoma.

PURPOSE: Locally advanced, unresectable basal cell carcinoma (LA BCC) can be treated with radiation therapy (RT), but locoregional control (LRC) rates are unsatisfactory. Vismodegib is a hedgehog pathway inhibitor (HPI) active in BCC that may radiosensitize BCC. We evaluated the combination of vismodegib and RT for patients with LA BCC. METHODS: In this multicenter, single-arm, phase II study, patients with unresectable LA BCC received 12 weeks of induction vismodegib, followed by 7 weeks of concurrent vismodegib and RT. The primary end point was LRC rate at 1 year after the end of treatment. Secondary end points included objective response, progression-free survival (PFS), overall survival (OS), safety, and patient-reported quality of life (PRQOL). RESULTS: Twenty-four patients received vismodegib; five were unable to complete 12 weeks of induction therapy. LRC was achieved in 91% (95% CI, 68 to 98) of patients at 1 year. The response rate was 63% (95% CI, 38 to 84) after induction vismodegib and 83% (95% CI, 59 to 96) after concurrent vismodegib and RT. With a median follow-up of 5.7 years, 1-year PFS and OS rates were 100% and 96%, and at 5 years PFS and OS rates were 78% and 83%, respectively. Distant metastasis or BCC-related death has not been observed. The most frequent treatment-related adverse events (AEs) were dysgeusia, fatigue, and myalgias occurring in 83%, 75%, and 75% of patients. No grade 4 to 5 treatment-related AEs occurred. PRQOL demonstrated clinically meaningful improvements in all subscales, with emotions and functioning improvements persisting for a year after the end of treatment. CONCLUSION: In patients with unresectable LA BCC, the combination of vismodegib and RT yielded high rates of LRC and PFS and durable improvements in PRQOL.

Carboplatin and paclitaxel after anti-PD-1 or anti-PD-L1 antibody therapy in recurrent and/or metastatic squamous cell carcinoma of head and neck.

BACKGROUND: The impact of concurrent chemotherapy and immunotherapy has been well characterized in patients with recurrent and metastatic head and neck squamous cell carcinoma (RM-SCCHN). Here, we report outcomes in patients treated sequentially with immune checkpoint inhibition (ICI) followed by carboplatin and paclitaxel. METHODS: Patients with RM-SCCHN treated with ICI followed by carboplatin/paclitaxel at a single institution were identified retrospectively. ICI therapy history, p16, and PD-L1 status were collected. The best overall response was assessed by RECIST v1.1. RESULTS: Twelve patients met inclusion criteria. Eight patients received pembrolizumab, three durvalumab, and one nivolumab. The median duration of ICI was 3.44 months, median PFS was 5.8 months, and median OS was 15.2 months. 66.7% of patients had an objective response on carboplatin/paclitaxel. CONCLUSIONS: Carboplatin/paclitaxel can induce objective responses in patients with prior treatment with ICI and clinical outcomes in this small series compare favorably to those seen in ICI naïve patients.

A review of the literature: How does prenatal opioid exposure impact placental health and fetal brain development?

In recent years, there has been a sixfold increase in the number of pregnant people with opioid use disorder (OUD). Rates of neonatal opioid withdrawal syndrome (NOWS), previously known as neonatal abstinence syndrome (NAS), have significantly increased in virtually every state and demographic group (Healthcare Cost Utilization Project, HCUP, 2010). NOWS is a condition resulting from chronic exposure to either therapeutic opioid use (e.g., medication for OUD, chronic pain conditions) or nonprescribed opioid use. To date, there is no known prenatal treatment to help decrease the risk of infants developing NOWS and subsequent neurodevelopmental outcomes. Given the increasing support for how placental signaling, or placental programming, may play a role in downstream pathology, prospective research investigating how the placenta is affected by chronic opioid exposure morphologically, histologically, and at the cellular level may open up potential treatment opportunities in this field. In this review, we discuss literature exploring the physiological roles of nitric oxide and dopamine not only in the vascular development of the placenta, but also in fetal cerebral blood flow, neurogenesis, neuronal differentiation, and neuronal activity. We also discuss histological preclinical studies that suggest chronic opioid exposure to induce some combination of placental dysfunction and hypoxia in a manner similar to other well-known placental pathologies, as denoted by the compensatory neovascularization and increased utilization of the placenta's supply of trophoblast cells, which play an essential role in placental angiogenesis. Overall, we found that the current literature, while limited, suggests chronic opioid exposure negatively impacts placental function and fetal brain development on a cellular and histopathological level. We conclude that it is worthwhile to consider the placenta as a therapeutic target with the ultimate goal of decreasing the incidence of NOWS and the long-term impacts of prenatal opioid exposure.

Horseshoe kidney: Morphologic features, embryologic and genetic etiologies, and surgical implications.

The horseshoe kidney (HSK) is the most common congenital abnormality of the upper urinary tract with an incidence of approximately 1 in 500 in the general population. Although individuals with HSK are often asymptomatic, they are at increased risk for neoplasms, infections, ureteropelvic obstruction secondary to lithiasis or vascular compression. Direct injury from trauma is increased in these individuals as is the risk of intraoperative complications secondary to damage involving the typically complex renal or adrenal vascular supply. We briefly review etiological factors including renal and urinary system embryology, genetic mutations, abnormalities related to faulty cell signaling, aberrant cell migration, and other possible causes including environmental exposures and trauma. In addition, we call attention to factors that might influence the success of surgical procedures in patients with HSK. We argue that an understanding of possible etiologies of the HSK and its different subtypes may be useful when planning surgical procedures or considering risk-benefit ratios associated with different surgical options. We briefly present the organization of a HSK in a 100-year-old male demonstrating an unusual vascular supply discovered during a dissection laboratory session in a medical school anatomy course. We describe the structure of the HSK, the position and relationships of the HSK to other structures within the abdomen, and the associated vascular relationships.

The gut microbiota and immune checkpoint inhibitors.

Although immunotherapy has been remarkably effective across multiple cancer types, there continues to be a significant number of non-responding patients. A possible factor proposed to influence the efficacy of immunotherapies is the gut microbiome. We discuss the results and implications of recent research on the relationship between the gut microbiome, our immune systems, and immune checkpoint inhibitor therapies including anti-CTLA-4 Ab and anti-PD-1 Ab. While the investigations all exhibit interesting results and conclusions, we find little congruence in the specific bacteria that were found favorable for antitumor responses. It is unclear whether the inconsistencies are due to differential approaches in study design (pre-clinical or clinical subjects, anti-CTLA-4 Ab or anti-PD-1 Ab), experimental methods and measurements (metagenomics sequencing and clustering variations) or subject population dynamics (differential cancer types and baseline characteristics). Moreover, we note studies regarding particular bacterial commensals and autoimmune diseases, which challenge findings from these investigations. We conclude that with the current research, clinical investigators can appreciate the critical role of gut microbiota in mediating immunostimulant response. However, prospective research exploring the biochemical mechanisms which commensal bacteria communicate with each other and the immune system is imperative to understand how they can be adjusted properly for higher immunotherapy response.