Diagnosis of pili trianguli et canaliculi by frozen section: A rapid and inexpensive method of diagnosis.

We present frozen section as a novel method in the diagnosis of pili trianguli et canaliculi that may serve as a more time- and resource- efficient alternative to current gold- standard electron microscopy. In this case series, three children between ages one and four presented with blonde hair unable to be combed into place. Frozen section was performed and evaluated under light microscopy with easy visualization of the hair shaft abnormality, consistent with the diagnosis of pili trianguli et canaliculi.

The Dynamic and Transient Immune Microenvironment in Locally Advanced Esophageal Adenocarcinoma Post Chemoradiation.

OBJECTIVE: The aim of this study was to assess the impact of chemoradiation on the immune microenvironment to influence and optimally design future neoadjuvant clinical trials. SUMMARY BACKGROUND DATA: Programmed death (PD)-1 inhibitors in metastatic gastroesophageal cancer have demonstrated response rates of approximately 25% in programmed death ligand-1 (PD-L1+) tumors. Unfortunately, the majority of patients do not respond. Therefore, a rationale strategy of combining immunotherapeutic agents with chemoradiation in earlier stage esophageal cancer may prevent metastatic disease in patients. METHODS: To determine the effects of chemoradiation on resected esophageal adenocarcinomas, we examined the immune microenvironment pre- and post-chemoradiation using immunohistochemistry, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and functional analysis of tumor-infiltrating lymphocytes. Additionally, to assess the duration and dependency of radiation-induced PD-L1 upregulation, a surgical rat reflux model of esophageal adenocarcinoma is used. First, tumor-bearing animals were dosed with single-fraction 13Gy or 16Gy radiation to determine safety, dose correlation, and PD-L1 upregulation using qRT-PCR post-radiation. Next, longitudinal PD-L1 expression levels within individual animals were determined using serial endoscopic biopsies at baseline, 1, 5, and 9 weeks post 16Gy radiation. RESULTS: The majority of cancers displayed enhanced interferon γ and activated CD8+ T lymphocytes at the tumor stroma interface. These tumors also demonstrated enhanced upregulation of PD-L1 and multiple other immune checkpoints including TIM3, GITR, IDO1, LAG3, OX40, and KIR. The animal model results indicated PD-L1 upregulation is dose-dependent and transiently elevated post radiation exposure. CONCLUSIONS: Collectively, these findings provide insights into the evolving immune landscape after chemoradiation and have significant implications for neoadjuvant trial designs that will combine radiotherapy with immune checkpoint inhibitors.

Preclinical Study of AUY922, a Novel Hsp90 Inhibitor, in the Treatment of Esophageal Adenocarcinoma.

OBJECTIVE: To assess the efficacy of heat-shock protein 90 (Hsp90) inhibitor, NVP-AUY922-AG (AUY922), in the treatment of esophageal adenocarcinoma (EAC) in vitro and in vivo. BACKGROUND: EAC is a leading cause of cancer death, and current treatment options are limited. Hsp90, a chaperone protein that regulates several oncoproteins, is upregulated in EAC, and may be a novel target for therapy. METHODS: In vitro, EAC cell lines were utilized to evaluate AUY922, alone and in combination with 5-fluorouracil (5-FU) and cisplatin. BrdU ELISA and flow cytometry were used to assess proliferation and measure apoptosis, respectively. Western blot and RT-PCR were performed to quantitate Hsp90 pathway expression. In vivo, esophagojejunostomy was performed on rats and treatment animals received AUY922 32 to 40 weeks postoperatively. Drug efficacy was evaluated with magnetic resonance imaging (MRI), endoscopic biopsy, gross histological evaluation, and Hsp90 pathway expression. RESULTS: In vitro, AUY922 demonstrated antiproliferative activity in both cell lines and showed enhanced efficacy with cisplatin and 5-FU. Western Blot and RT-PCR demonstrated downregulation of CDK1 and CDK4 and upregulation of Hsp72. In vivo, AUY922 showed decrease in tumor volume in 36.4% of rats (control = 9.4%), increase in 9.1% (control = 37.5%), and stable disease in 54.5% (control = 43.7%). Necropsy confirmed the presence of EAC in 50% of treatment animals and 75% of control animals. mRNA expression, pre- and posttreatment, demonstrated significant downregulation of MIF, Hsp70, Hsp90ß, and CDK4, and upregulation of Hsp72. CONCLUSIONS: AUY922 exhibits antitumor efficacy in vitro and in vivo for EAC, suggesting the need for human clinical trials.

Home health care with telemonitoring improves health status for older adults with heart failure.

Home telemonitoring can augment home health care services during a patient's transition from hospital to home. Home health care agencies commonly use telemonitors for patients with heart failure although studies have shown mixed results in the use of telemonitors to reduce rehospitalizations. This randomized trial investigated if older patients with heart failure admitted to home health care following a hospitalization would have a reduction in rehospitalizations and improved health status if they received telemonitoring. Patients were followed up to 180 days post-discharge from home health care services. Results showed no difference in the time to rehospitalization or emergency visit between those who received telemonitoring versus usual care. Older heart failure patients who received telemonitoring had better health status by home health care discharge than those who received usual care. Therefore, for older adults with heart failure, telemonitoring may be an important adjunct to home health care services to improve health status.

Acute fibrinous and organizing pneumonia in a patient with Sjogren's syndrome.

Acute fibrinous and organizing pneumonia (AFOP) is a histological pattern characterized by intra-alveolar fibrin deposition and associated organizing pneumonia. AFOP has been associated with many rheumatologic disorders in the literature but has not been described in association with Sjogren's syndrome. This paper shows a rare association of AFOP with Sjogren's syndrome. Patient's symptoms promptly improved after treatment with steroid.

Primary tumor microRNA signature predicts recurrence and survival in patients with locally advanced esophageal adenocarcinoma.

Esophageal adenocarcinoma (EAC) is an aggressive cancer necessitating the development of improved risk stratification tools for personalized care. Previously, microRNAs have been shown to correlate with the progression and prognosis of various cancer types; however, the value in EAC remains largely unexplored. We performed global microRNA profiling on 32 formalin-fixed, paraffin-embedded EAC specimens to identify microRNAs associated with progression. Literature search and pathway analysis further refined output to five significantly deregulated candidate biomarkers. Four of the five microRNAs (miR-652-5p, miR-7-2-3p, miR-3925-3p, and miR-219-3p) were validated by qRT-PCR. Survival outcomes were evaluated in testing set of 26 stage II/III EAC patients to determine the prognostic relevance of the selected microRNAs. In the testing set, miR-652-5p and miR-7-2-3p expressions were significantly associated with progression-free survival (p-value = .00771 and p-value = .00293). The highest area under receiver operating characteristic (ROC) curve was 0.8212 for the combination of miR-652-5p and miR-7-2-3p. Collectively, our findings demonstrated that the miR-652-5p/miR-7-2-3p signature may serve as a promising prognostic marker in patients with locally advanced EAC.

Body mass index and 25 hydroxyvitamin D status in patients with and without heart failure.

The purpose of this pilot study was to assess the association between 25-hydroxyvitamin D (25[OH]D) concentrations, vitamin D intake, and sunlight exposure in patients with heart failure (HF) compared with healthy volunteers. Fourteen healthy volunteers 50 and older were recruited to compare with 14 patients with HF. Healthy volunteers were compared with HF patients by serum 25(OH)D concentrations, dietary vitamin D intake, weekly sunlight exposure, and other covariates. Independent sample t tests and linear regression models were used to compare differences between healthy volunteers and patients with HF. The mean serum 25(OH)D concentration was not significantly different between groups (healthy volunteers 25.7 ± 11.1 ng/mL, patients with HF 20.4 ± 10.2 ng/mL; P=.2) and no group effect was found in any multivariable models. Body mass index regardless of group was found to be inversely associated with serum 25(OH)D concentrations (P=.025). There was no difference in the dietary intake of vitamin D or calcium between groups. The healthy volunteers had a significantly greater amount of sunlight exposure but this did not result in higher 25(OH)D when compared with those with HF. Our findings suggest that body mass index has an important relationship with 25(OH)D concentrations regardless of a person being healthy or having HF.

Pleural silicone granuloma mimics pleural metastasis: Ruptured breast implant with silicone fistulising along a remote thoracotomy scar.

Silicone gel from ruptured implants can migrate to locations such as the chest wall, axillae, and upper extremities, resulting in granulomatous inflammation. Pleural silicone granulomas have rarely been reported in the literature. This is a rare case of pleural silicone granuloma, which demonstrates that silicone gel from an extracapsular implant rupture can fistulise into the pleural space along a remote thoracotomy scar.