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Background Patients with failed endoscopic retrograde cholangiopancreatography (ERCP) are conventionally offered percutaneous transhepatic biliary drainage (PTBD). While PTBD is effective, it is associated with catheter-related complications, pain, and poor quality of life. Endoscopic ultrasound-guided biliary drainage (EUS-BD) is a minimally invasive endoscopic option increasingly offered as an alternative to PTBD. We compare outcomes of EUS-BD and PTBD in patients with biliary obstruction at a single tertiary care center. Methods A retrospective review was performed in patients with biliary obstruction who underwent EUS-BD or PTBD after failed ERCP from June 2010 through December 2014 at a single tertiary care center. Patient demographics, procedural data, and clinical outcomes were documented for each group. The aim was to compare efficacy and safety of EUS-BD and PTBD and evaluate predictors of success. Results A total of 60 patients were included (mean age 67.5 years, 65 % male). Forty-seven underwent EUS-BD, and thirteen underwent PTBD. Technical success rates of PTBD and EUS-BD were similar (91.6 vs. 93.3 %, p  = 1.0). PTBD patients underwent significantly more re-interventions than EUS-BD patients (mean 4.9 versus 1.3, p  < 0.0001), had more late (>24-h) adverse events (53.8 % vs. 6.6 %, p  = 0.001) and experienced more pain (4.1 vs. 1.9, p  = 0.016) post-procedure. In univariate analysis, clinical success was lower in the PTBD group (25 vs. 62.2 %, p  = 0.03). In multivariable logistic regression analysis, EUS-BD was the sole predictor of clinical success and long-term resolution (OR 21.8, p  = 0.009). Conclusion Despite similar technical success rates compared to PTBD, EUS-BD results in a lower need for re-intervention, decreased rate of late adverse events, and lower pain scores, and is the sole predictor for clinical success and long-term resolution. EUS-BD should be the treatment of choice after a failed ERCP.

INTRODUCTION:Myeloid sarcoma is a rare tumor characterized by a tissue mass of myeloid progenitor cells occurring outside of the bone marrow. Myeloid sarcoma can occur de novo or overlap with acute myeloid leukemia (AML). As with AML, myeloid sarcoma may also present as a blast transformation of myelodysplastic syndrome or neoplasm.CASE DESCRIPTION/METHODS:A 65-year-old male was transferred to our hospital for hematochezia after a cecal polypectomy. Two days prior to transfer, the patient underwent screening colonoscopy for colorectal cancer at an outside hospital. During the procedure, a large carpeted, sessile polyp was seen overlying the cecal fold. Endoscopic removal was attempted but was unsuccessful given the polyp’s location and size. Pathology from the partially removed polyp revealed a tubulovillous adenoma. His hemoglobin was 6.5 g/dL (13.0–17.0 g/dL) and white blood cell count was 70 M/μL (4.20–5.60 M/μL). Following blood transfusions and hemodynamic stabilization, repeat colonoscopy and bone marrow biopsy were performed. The polypectomy site revealed flat, polypoid ulcerated and friable tissue with multiple areas of bleeding and clot (Figure 1). Despite hemostatic clip placement and thermal therapy to treat areas of active oozing, the lesion continued to bleed. The surgical team was activated given known residual adenomatous tissue and the patient underwent a successful right hemicolectomy. Pathology of the surgical specimen showed a tubulovillous adenoma with focal high-grade dysplasia and central ulceration with fibrinous exudate and submucosal hemorrhage. In addition, there were immature myeloid cells infiltrating the submucosa underneath this polyp. Furthermore, sheets of myeloblasts, positive for CD34 and CD117, within the submucosa also formed a separate ulcerated, plaque-like, 1.0 cm mass distal to the polyp (Figure 2). Bone marrow biopsy showed a 70% cellular marrow with nearly 20% myeloblasts. The patient had both a tubulovillous adenoma with an infiltrating adjacent myeloid sarcoma.DISCUSSION:While myeloid sarcoma can affect any organ, they most commonly infiltrate the skin or gums. Colonic involvement is extremely rare. Treatment for myeloid sarcomas is identical to that of AML, even if there no evidence of bone marrow involvement.

INTRODUCTION:Sarcoidosis is a multisystem disease primarily involving the lung. Skin, eyes, lymph nodes, spleen, liver, bones, exocrine glands, heart, kidneys, and central nervous system are the most common extrapulmonary sites involved. Clinically apparent gastrointestinal (GI) sarcoidosis is rare involving 0.1 to 0.9 percent of patients with sarcoidosis. The most commonly involved portion of the GI tract is the stomach, although sarcoidosis of the esophagus, appendix, colon, rectum, and pancreas have been reported in the literature.CASE DESCRIPTION/METHODS:A 73-year-old African American male was found to have pancreatic duct dilation on a computed tomography scan of abdomen done for investigation of mild epigastric abdominal pain that started a few months prior to presentation. He described the pain as dull, non-radiating, aggravated when hungry, subsided with food intake and associated with bloating. He had a past medical history of hypertension, hypothyroidism, and sarcoidosis involving lymph nodes and liver (not on treatment). He had no family history of GI cancer. He was a non-smoker and non-alcoholic. On presentation, his vital signs were normal; his abdomen was soft and non-tender, with normoactive bowel sounds and no masses or organomegaly. He had a normal calcium level of 9.7 mg/dL and his liver panel was significant for slightly elevated serum alkaline phosphatase, AST, ALT levels, with normal serum bilirubin. Magnetic resonance imaging showed 1.2 cm mass in the body of the pancreas obstructing the pancreatic duct and another 1.1 cm mass in the head of the pancreas concerning for malignancy. He underwent endoscopic ultrasonography with fine needle aspiration cytology of both pancreatic masses which showed numerous non-caseating granulomas consistent with sarcoidosis. Special stains for fungi and tuberculosis were negative.DISCUSSION:Less than 30 cases of biopsy-proven pancreatic sarcoidosis have been reported in the literature. Patients can have direct involvement of pancreas with sarcoidosis or 1, 25-dihydroxy vitamin D3 mediated hypercalcemia causing hypercalcemic pancreatitis. About three fourths of patients with pancreatic sarcoidosis have bilateral hilar adenopathy on chest radiography. On imaging, these patients demonstrate either a pancreatic mass (or masses) or a diffuse nodular pancreas. A biopsy is essential to distinguish between sarcoidosis, mycobacterial or fungal infection, and cancer. Treatment is usually conservative or with glucocorticoids.

During the COVID-19 pandemic, care homes for older adults in England implemented isolation, social distancing and other restriction measures to help protect residents from contracting the virus. Little was known about the physical and psychological impacts that these measures would have upon residents and their relatives. To explore the experiences of residents and their relatives of living restricted lives during the pandemic. This qualitative study was conducted as part of a 12-month, mixed-methods, phased design. From six purposively sampled care homes in England, 17 purposively sampled residents (all older adults) and 17 purposively sampled relatives participated in an individual, on-line interview, where they discussed their experiences of the restrictive measures implemented within their care home. Interviews were audio- and video-recorded with participants' permission and analysed using an inductive orientation to thematic analysis, with coding and theme development driven by the data content. Participants' experiences of care home restrictions varied; their impact was influenced by the existing pattern of relationships that residents and their relatives maintained within and beyond the care home. It was further influenced by the fact that many residents and relatives were still learning how to manage their relationships in the new context of living in a care home. Social distancing measures made care homes feel less homely and denied residents, staff and relatives physical touch and other forms of non-verbal communication. Many residents expressed a broad sense of gratitude that was associated with safety and well-being beyond the pandemic. As older adults, they put the pandemic, and its associated restrictions, within the larger context of their lives. Learning from the COVID-19 pandemic is paramount for governments, societies, policy makers, care home providers, care homes and their staff, residents and their families and friends, and researchers. Our study makes an important contribution as one of the first to study the impact of implementing isolation, social distancing and other restrictive measures for care home residents and their relatives in England.

ASP4345, a novel dopamine D1 receptor positive allosteric modulator, is being evaluated for the treatment of cognitive impairment associated with schizophrenia (CIAS). This phase 1 multiple ascending-dose study (NCT02720263) assessed the safety, tolerability, and pharmacodynamics of ASP4345 in patients with schizophrenia/schizoaffective disorder. Pharmacodynamic assessments were Cogstate cognitive tests and electrophysiological biomarkers, including gamma-band power and phase synchronization in response to 40-Hz auditory steady-state stimulation, as well as mismatch negativity (MMN) and P3a event-related potentials. The sample size determination was based on standard practice in assessing safety and tolerability of a new chemical entity. Data were summarized by conversion of this data into effect sizes using descriptive and inferential statistics. A total of 36 randomized patients received ASP4345 (3, 15, 50, and 150 mg; n = 9 each dose) and 12 patients received placebo. Patients in the ASP4345 group experienced 73 treatment-emergent adverse events (TEAEs) and 34 TEAEs were reported for the placebo group. The most common TEAEs were headache and somnolence and nearly all TEAEs were mild in severity. No changes in mood or self-reports of suicidal ideation/behavior were observed. Improvements in performance on cognitive tests were noted, which suggests a potential improvement in psychomotor function and visual attention. Furthermore, positive changes in neurophysiological biomarkers (auditory steady-state response [ASSR] and MMN) suggest improvement in information processing. The findings need to be confirmed in studies with a larger patient population. Nonetheless, the trends in safety and pharmacodynamic data support further clinical development of ASP4345 for the treatment of CIAS.

Friendship is an essential part of human experience, involving ideas of love and morality as well as material and pragmatic concerns. Making and having friends is a central aspect of everyday life in all human societies. Yet friendship is often considered of secondary significance in comparison to domains such as kinship, economics and politics. How important are friends in different cultural contexts? What would a study of society viewed through the lens of friendship look like? Does friendship affect the shape of society as much as society moulds friendship? Drawing on long-term ethnographic fieldwork in Asia, the Middle East, Africa, Latin America and Europe, this volume offers answers to these questions and examines the ideology and practice of friendship as it is embedded in wider social contexts and transformations.

IntroductionIntracranial meningiomas rarely present with multiple lesions. To the best of our knowledge, current literature regarding meningiomatosis (MM) is mostly comprised of small case series and individual reports. Hence, survival outcome data are limited. The Objective of this study is to explore the influence of sex, age, and number of lesions on overall survival (OS) in patients with MM.MethodsWe obtained demographic and clinical data from the surveillance, epidemiology, and end results program (SEER) on adult patients diagnosed with meningiomas from 1975 to 2017. Univariable and multivariable analyses were conducted to assess whether number of lesions, age, and sex had a significant influence on OS.Results99,918 cases were included. Results showed that MM patients had a significantly decreased OS when compared to patients with a single lesion (median OS of 94 and 180 months, respectively; p < 0.001). Further analysis showed a progressive decrease on OS for every additional lesion; 2 (HR 1.659 [CI 95% 1.612–1.708], p < 0.001), 3 (HR 1.877 [CI 95% 1.773–1.988], p < 0.001), and ≥ 4 (HR 2.116 [CI 95% 1.886–2.373], p < 0.001). When assessing for sex differences, female patients had increased OS (HR 0.778 [CI 95% 0.743–0.815], p < 0.001) and decreased risk of developing MM (HR 0.809 [CI 95% 0.784–0.835], p < 0.001).ConclusionIncreasing number of meningiomas has a significant negative impact on OS, with a progressive decrease on survival for every additional lesion. Furthermore, female patients had increased OS and decreased risk to develop MM.

Purpose The purpose of the study is to evaluate the effect of renal impairment (RI) and end-stage renal disease (ESRD) on the pharmacokinetics (PK) of isavuconazole and the inactive cleavage product, BAL8728. Methods A single intravenous dose of the prodrug isavuconazonium sulfate (372 mg, equivalent to 200 mg isavuconazole and 75 mg of BAL8728 cleavage product) was administered to healthy controls (parts 1 and 2) and participants with mild, moderate, or severe RI (part 2) or ESRD (part 1); ESRD participants received two doses of 200 mg isavuconazole, 1 h post-dialysis (day 1) and prior to dialysis (day 15). Plasma PK parameters for isavuconazole included maximum concentration ( C max ), area under the concentration–time curve (AUC) from time of dose to 72 h (AUC 72 ), AUC extrapolated to infinity (AUC ∞ ), AUC to last measurable concentration (AUC last ), half-life ( t ½ h), volume of distribution ( V z ), and total clearance (CL), for the healthy control group versus those with mild, moderate, or severe RI or ESRD. Results Isavuconazole C max values were 4% higher in mild RI and 7, 14, and 21% lower in participants with moderate RI, severe RI, or ESRD versus the healthy control group, respectively. When hemodialysis occurred post-dose (day 15), participants with ESRD had a 30% increase in AUC 72 for isavuconazole in parallel with reduction of extracellular volume induced by dialysis. Exposure (AUC ∞ and AUC last ) was not significantly different for participants with mild, moderate, or severe RI versus healthy controls although there was considerable variability. The t 1/2 (day 1) was 125.5 ± 63.6 h (healthy control group), 204.5 ± 82.6 h (ESRD group) in part 1, and 140.5 ± 77.7 h (healthy control group), 117.0 ± 66.2 h (mild RI), 158.5 ± 56.4 h (moderate RI), and 145.8 ± 65.8 L/h (severe RI) in part 2. CL was 2.4 ± 0.8 L/h (healthy control group) and 2.9 ± 1.3 L/h (ESRD group) in part 1 and 2.4 ± 1.2 L/h (healthy control group), 2.5 ± 1.0 L/h (mild RI), 2.2 ± 0.8 L/h (moderate RI), and 2.4 ± 0.8 L/h (severe RI) in part 2. The V z was 382.6 ± 150.6 L in the healthy control group and 735.6 ± 277.3 L in ESRD patients on day 1 in part 1 of the study. In part 2 of the study, V z was 410.8 ± 89.7 L in the healthy control group, 341.6 ± 72.3 L in mild RI, 509.1 ± 262.2 L in moderate RI, and 439.4 L in severe RI. Conclusions Based on the findings of this study, dose adjustments of isavuconazole are unlikely to be required in individuals with RI or in those with ESRD who receive hemodialysis.

Evaluation of lesions affecting the parotid gland is often challenging to both clinicians and radiologists. This article reviews parotid anatomy and function, as it relates to various lesions that may occur within the gland. Key morphlogic features of lesions are discussed with an emphasis on those that warrant biopsy and those that do not need biopsy. Various biopsy methods using ultrasound and computed tomography are reviewed.

Mastoid air cell fluid is a commonly seen, but often dismissed finding. Given the location of the mastoid portion of the temporal bone and its location adjacent to vital structures, a careful evaluation is important for the emergency radiologist. While occasionally benign, fluid within the mastoid air cells can be an early sign of more severe pathology, and familiarity of regional anatomy allows for early identification of disease spread. This article describes the important anatomy, the common pathologies, and a radiologic approach to assessing the mastoid air cells in order to guide referring clinicians.