Radiation and systemic immunotherapy for metastatic uveal melanoma: a clinical retrospective review.

Introduction: Metastatic uveal melanoma (mUM) is a difficult to treat disease. The liver is the primary site of metastasis in most patients, though uveal melanoma spreads widely in advanced disease. The only FDA approved immunotherapy medication for metastatic uveal melanoma is the HLA-A02:01 restricted bispecific T cell engager drug, Tebentafusp. Checkpoint inhibitor strategies and combination approaches have been tried with some limited success. We describe our experience treating patients at the University of Minnesota. Methods: Patients were included if they had biopsy-confirmed mUM. Twenty-five (25) patients meeting the criteria were identified. Medical records were reviewed and data extracted for patient baseline characteristics and response to treatments. Results: Median time to metastasis from the time of local therapy to the eye was 14.2 months (IQR; 9.3-22.0), and first site of metastasis was liver in 92% of patients. Two patients (8%) did not receive systemic therapy or radiation therapy for metastatic disease. Twenty-three (92%) patients received systemic therapy, 13 patients (52%) received ipilimumab-nivolumab as the first-line, while 4 patients (16%) received pembrolizumab. Landmark survival analysis by receipt of systemic therapy and radiation therapy treatments within 6 months of biopsy confirmed diagnosis is shown. Twenty patients (80%) received systemic therapy within 6 months of mUM diagnosis. Thirteen patients (52%) received liver directed radiation therapy within 6 months of mUM diagnosis. Discussion: Within our cohort, there was no overall survival benefit for patients receiving treatment of metastatic disease within 6 months of mUM diagnosis, versus those electing later or no treatment at all. There was remarkable clinical activity of ipilimumab and nivolumab in a subset of patients with mUM, in agreement with prior studies, and metastatic PD-L1 positive tumors were associated with a prolonged survival.

Sleep Loss the night before surgery and incidence of postoperative delirium in adults 65-95 years of age.

STUDY OBJECTIVES: To describe the association between preoperative sleep disruption and postoperative delirium. METHODS: Prospective cohort study with six time points (3 nights pre-hospitalization and 3 nights post-surgery). The sample included 180 English-speaking patients ≥65 years old scheduled for major non-cardiac surgery and anticipated minimum hospital stay of 3 days. Six days of wrist actigraphy recorded continuous movement to estimate wake and sleep minutes during the night from 22:00 to 05:59. Postoperative delirium was measured by a structured interview using the Confusion Assessment Method. Sleep variables for patients with (n = 32) and without (n = 148) postoperative delirium were compared using multivariate logistic regression. RESULTS: Participants had a mean age of 72 ± 5 years (range 65-95 years). The incidence of postoperative delirium during any of the three postoperative days was 17.8%. Postoperative delirium was significantly associated with surgery duration (OR = 1.49, 95% CI 1.24-1.83) and sleep loss >15% on the night before surgery (OR = 2.64, 95% CI 1.10-6.62). Preoperative symptoms of pain, anxiety and depression were unrelated to preoperative sleep loss. CONCLUSIONS: In this study of adults ≥65 years of age, short sleep duration was more severe preoperatively in the patients who experienced postoperative delirium as evidenced by sleep loss >15% of their normal night's sleep. However, we were unable to identify potential reasons for this sleep loss. Further investigation should include additional factors that may be associated with preoperative sleep loss to inform potential intervention strategies to mitigate preoperative sleep loss and reduce risk of postoperative delirium.

CT features of rounded atelectasis in chronic inflammatory pleural effusions in cats and dogs.

Rounded atelectasis is well described in human medicine as focal lung deformation and collapse secondary to inflammatory pleural effusions and pleuritis. Specific CT features (round to ovoid soft tissue pulmonary attenuations, creation of an acute angle with the adjoining visceral pleura, and the presence of perinodular comet tail signs) support the diagnosis of rounded atelectasis in humans so that further diagnostic workup is not necessary in defining the nodules. In this retrospective case series, we described the CT characteristics of rounded atelectasis in eight cats and three dogs diagnosed with restrictive pleuritis secondary to either a chylothorax or pyothorax. Thirty-six soft tissue attenuating pulmonary nodular lesions were identified on CT. Comet tail signs, consisting of bundles of bronchi and vessels coalescing into the pulmonary nodules, were associated with 92% of the nodules (33/36), and 92% of the nodules abutted and created an acute angle with the pleura (33/36). Other prevalent features included location in gravity-dependent regions of the lung lobes (33/36, 92%), blurred hilar margins with sharper pleural margins of the nodules (33/36, 92%), presence of air bronchograms (30/36, 83%), homogeneous contrast-enhancement (23/36, 64%), and volume loss of the affected lung lobe (22/36, 61%). Pulmonary malignant neoplasms were not found cytologically (6/11 patients) or histologically (5/11 patients). To avoid a misdiagnosis of neoplasia, veterinary radiologists should be aware of the CT features of rounded atelectasis and consider it as a differential for pulmonary nodular lesions in patients with concurrent inflammatory pleural effusion and pleuritis.

The Impact of Surgery duration and Surgery End Time on Postoperative Sleep in Older Adults.

OBJECTIVES/BACKGROUND: Sleep disruption is prevalent in older patients. No previous studies have considered the impact of surgery duration or surgery end time of day on postoperative sleep disruption. Accordingly, we examined the duration of surgery and surgery end times for associations with postoperative sleep disruption. METHODS: Inclusion criteria were patients ≥ 65 years of age undergoing major, non-cardiac surgery. Sleep disruption was measured by wrist actigraphy and defined as wake after sleep onset (WASO) during the night, or inactivity/sleep time during the day. The sleep opportunity window was set from 22:00 to 06:00 which coincided with "lights off and on" in the hospital. WASO during this 8-hour period on the first postoperative day was categorized into one of three groups: ≤ 15%, 15-25%, and > 25%. Daytime sleep (inactivity) during the first postoperative day was categorized as ≤ 20%, 20-40%, and > 40%. Statistical analyses were conducted to test for associations between surgery duration, surgery end time and sleep disruption on the first postoperative day and following night. RESULTS: For this sample of 156 patients, surgery duration ≥ 6 hours and surgery end time after 19:00 were not associated with WASO groups (p = 0.17, p = 0.94, respectively). Furthermore, daytime sleep was also not affected by surgery duration or surgery end time (p = 0.07, p = 0.06 respectively). CONCLUSION: Our hypothesis that patients with longer duration or later-ending operations have increased postoperative sleep disruption was not supported. Our results suggest the pathophysiology of postoperative sleep disruption needs further investigation.

Reductive defluorination of Perfluorooctanesulfonic acid (PFOS) by hydrated electrons generated upon UV irradiation of 3-Indole-acetic-acid in 12-Aminolauric-Modified montmorillonite.

Per-and poly-fluoroalkyl substances (PFASs) are a class of persistent compounds that are resistant to degradation. Here we developed an effective method of degrading perfluorooctanesulfonate (PFOS) by hydrated electrons (eaq-) that are generated from 3-indole-acetic-acid (IAA) upon UV irradiation. The method takes advantage of spatial proximity of IAA and PFOS by their co-sorption to an organic polymer, 12-aminolauric acid (ALA), which was pre-intercalated into the interlayer space of an expandable clay mineral, montmorillonite. The interlayer spacing of this clay nanocomposite is greatly expanded relative to unmodified montmorillonite. The maximum adsorption capacity of IAA and PFOS is 168 and 1550 mmol/kg, respectively. This process achieved 40-70% defluorination of a 10 ppm PFOS solution at neutral pH in a 325 mL vessel. The presence of bicarbonate and chloride ions, or natural groundwater showed a minimal impact on PFOS degradation. Based on identification of prominent degradation products, a degradation pathway is proposed, where the primary degradation process is breakage of the C-F bonds (with fluorine replaced by hydrogen), with some cleavage of the CC bond. This approach provides an alternative for treating concentrated PFAS solutions under ambient conditions.

Chrysiasis: Gold Aggregates Around a Nevus and Osteoma Cutis.

ABSTRACT: Parenteral gold has historically been used to treat several conditions, including rheumatoid arthritis. Gold administration leads to a variety of cutaneous reactions, including chrysiasis, which is a permanent blue-grey hyperpigmentation of the skin due to dermal gold deposition. In this report, we describe the case of a patient who received parenteral gold injections 22 years before the onset of her chrysiasis for the treatment of rheumatoid arthritis. Biopsy of the macules showed dermal gold deposits aggregating around a melanocytic nevus, as well as around preexisting osteoma cutis. To the authors' knowledge, this is the first report in the literature describing a case of chrysiasis with gold deposits concentrated around a melanocytic nevus and an area of osteoma cutis.

Activation of Massive Transfusion for Elderly Trauma Patients.

Massive transfusion protocol (MTP) is used to resuscitate patients in hemorrhagic shock. Our goal was to review MTP use in the elderly. All trauma patients who required activation of MTP at an urban Level I trauma center from January 1, 2011 to December 31, 2013 were reviewed retrospectively. Elderly was defined as age ≥ 60 years. Sixty-six patients had MTP activated: 52 nonelderly (NE) and 14 elderly (E). There were no statistically significant differences between the two cohorts for gender, injury severity score, head abbreviated injury scale, emergency department Glasgow Coma Scale, initial hematocrit, intensive care unit length of stay, or hospital length of stay. Mean age for NE was 35 years and 73 years for E (P < 0.01). Less than half (43%) of E patients with activation of MTP received 10 or more units of blood products compared with 69 per cent of the NE (P = 0.07). Mortality rates were similar in the NE and the E (53%vs 50%, P = 0.80). After multivariate analysis with Glasgow Coma Scale, injury severity score, and blunt versus penetrating trauma, elderly age was not a predictor of mortality after MTP (P = 0.35). When MTP is activated, survival to discharge in elderly trauma patients is comparable to younger patients.