Citations

AbstractBackgroundThis study presents oncologic outcomes after transoral robotic surgery (TORS) ± adjuvant therapy for oropharyngeal squamous cell carcinoma (SCC).MethodsThree hundred fourteen patients undergoing TORS ± adjuvant therapy for oropharyngeal SCC from May 1, 2007, to May 31, 2015, are analyzed.ResultsMedian follow‐up was 3.3 years (interquartile range [IQR] 1.8‐5.3 years; range 1 day to 9.3 years). Estimated locoregional recurrence‐free survival, distant metastasis‐free survival (DMFS), overall survival (OS), and cancer‐specific survival (CSS) rates (95% confidence interval [CI] number still at risk) at 5 years after surgery were 92% (88‐95; 92), 90% (86‐94; 92), 86% (82‐92; 98), and 94% (91‐97; 98), respectively. Negative margins were achieved in 98% of cases. The adult comorbidity evaluation (ACE)‐27 comorbidity index, human papillomavirus (HPV) status, pathologic N classification, and number of attempts to clear margins were associated with death due to cancer (P = .003, P = .002, P = .030, and P = .002, respectively).ConclusionThe need to take ≥2 margins to achieve resection portends an increased risk of locoregional recurrence and death due to disease in oropharyngeal SCC.

Acquired angioedema due to C1 inhibitor deficiency (C1INH-AAE) is a rare and potentially fatal syndrome of bradykinin-mediated angioedema characterized by episodes of angioedema without urticaria. It typically manifests with nonpitting edema of the skin and edema in the gastrointestinal (GI) tract mucosa or upper airway. Edema of the upper airway and tongue may lead to life-threatening asphyxiation. C1INH-AAE is typically under-diagnosed because of its rarity and its propensity to mimic more common abdominal conditions and allergic reactions. In this article, we present the case of a 62-year-old male with a history of recently diagnosed chronic lymphocytic leukemia (CLL) who presented to our hospital with recurrent abdominal pain, initially suspected to haveClostridium difficilecolitis and diverticulitis. He received a final diagnosis of acquired angioedema due to C1 esterase inhibitor deficiency due to concomitant symptoms of lip swelling, cutaneous nonpitting edema of his lower extremities, and complement level deficiencies. He received acute treatment with C1 esterase replacement and icatibant and was maintained on C1 esterase infusions. He also underwent chemotherapy for his underlying CLL and did not experience further recurrence of his angioedema.

AbstractBackgroundTransthoracic impedance measurements (TIM) is primarily used for minute ventilation rate adaptive sensors in pacemakers. With elevated impedance, the TIM electrical signal itself is oversensed, causing device malfunction.ObjectiveWe report an increased incidence of TIM oversensing.MethodRetrospective chart review. We review existing records of 18 patients who have demonstrated device malfunction with TIM oversensing.ResultsWe have found a 1.8% incidence of TIM‐related oversensing in our patient population of 959 patients with contemporary Boston Scientific (Marlborough, MA, USA) pacemakers and cardiac resynchronization therapy pacemakers. One patient experienced a syncopal episode.ConclusionOversensing with pacing inhibition is apparent with the potential of adverse effects to patients.

Intravenous infusion of oncolytic reovirus in patients leads to infection of brain tumors, infiltration by cytotoxic T cells, and up-regulation of PD-L1.

BACKGROUND: Thrombocytopenia is frequently encountered in critically ill patients, often resulting in prophylactic transfusion of platelets for the prevention of bleeding complications. However, the efficacy of this practice remains unclear. The objective of this study was to determine the relationship between prophylactic platelet transfusion and bleeding complications in critically ill patients. METHODS: This is a retrospective cohort study of adults admitted to surgical, medical, or combined medical-surgical intensive care units (ICUs) at a single academic institution between January 1, 2009, and December 31, 2013. Inclusion criteria included age ≥18 years and a platelet count measured during ICU admission. Propensity-matched analyses were used to evaluate associations between prophylactic platelet transfusions and the outcomes of interest with a primary outcome of red blood cell transfusion in the ensuing 24 hours and secondary outcomes of ICU and hospital-free days and changes in sequential organ failure assessment scores. RESULTS: A total of 40,693 patients were included in the investigation with 3227 (7.9%) receiving a platelet transfusion and 1065 (33.0%) for which platelet transfusion was prophylactic in nature. In propensity-matched analyses, 994 patients with prophylactic platelet transfusion were matched to those without a transfusion. Patients receiving prophylactic platelets had significantly higher red blood cell transfusion rates (odds ratio 7.5 [5.9–9.5]; P < .001), fewer ICU-free days (mean [standard deviation] 20.8 [9.1] vs 22.7 [8.3] days; P = .004), fewer hospital-free days (13.0 [9.7] vs 15.8 [9.4] days; P < .001), and less improvement in sequential organ failure assessment scores (mean decrease of 0.2 [3.6] vs 1.8 [3.3]; P < .001) in the subsequent 24 hours. These findings appeared robust, persisting in multiple predefined sensitivity analyses. CONCLUSIONS: Prophylactic administration of platelets in the critically ill was not associated with improved clinical outcomes, though residual confounding may exist. Further investigation of platelet transfusion strategies in this population is warranted.

AbstractThe Melatonin Osteoporosis Prevention Study (MOPS) demonstrated that nightly melatonin resulted in a time‐dependent decrease in equilibrium ratios of serum osteoclasts and osteoblasts in perimenopausal women. This study examines mechanisms related to the ratios of osteoblasts and osteoclasts using coculture models (transwell or layered) of human mesenchymal stem cell (MSC) and human peripheral blood monocytes (PBMCs). Human MSC/PBMC cocultures exposed to melatonin in osteogenic (OS+) medium for 21 days induced osteoblast differentiation and mineralization; however, only in layered cocultures did melatonin inhibit osteoclastogenesis. Melatonin effects were mediated through MT2 melatonin receptors, MEK1/2, and MEK5. In layered but not transwell cocultures, melatonin increased OPG:RANKL ratios by inhibiting RANKL, suggesting that contact with osteoclasts during osteoblastogenesis inhibits RANKL secretion. Melatonin modulated expression of ERK1/2, ERK5, β1 integrin, GLUT4, and IRβ that was dependent upon the type of coculture; however, in both cultures, melatonin increased RUNX2 and decreased PPARγ expression, indicating a role for metabolic processes that control osteogenic vs adipogenic cell fates of MSCs. Furthermore, melatonin also has osteoblast‐inducing effects on human adipose‐derived MSCs. In vivo, one‐year nightly melatonin (15 mg/L) given to neu female mice in their drinking water increased pErk1/2, pErk5, Runx2, and Opg and Rankl levels in bone consistent with melatonin's already reported bone‐enhancing effects. Finally, analysis of daily logs from the MOPS demonstrated a significant improvement in mood and perhaps sleep quality in women receiving melatonin vs placebo. The osteoblast‐inducing, bone‐enhancing effects of melatonin and improvement in quality of life suggest that melatonin is a safe and effective bone loss therapy.

AbstractWe conducted a surveillance epidemiology and end results (SEER)‐based analysis to describe the incidence and characteristics of second primary acute lymphoblastic leukemia (sALL) among adults (≥18 years) with a history of primary malignancies (1M). Standardized incidence ratios (SIRs) of sALL cases were calculated by site and 1M stage. We also evaluated the differences in 5‐year sALL survival by age, site, and extent of 1M, latency of sALL after 1M, and evidence of underlying racial/ethnic disparity. We identified 10,956 patients with de‐novo/primary acute lymphoblastic leukemia (1ALL) and 772 with sALL. Women (49.1% vs. 42.9%), white patients (72.0% vs. 59.5%), older patients (58.8% vs. 25.2%; age ≥65 years), and patients diagnosed between 2003 and 2012 (66.8% vs. 53.9%) had a higher proportion of sALL compared with 1ALL. There was a significantly inferior median 5‐year survival for sALL patients compared to 1ALL (6 vs. 15 months; HR 1.20, 95% CI 1.10–1.31, P < 0.001). The median latency period was 60.0 months; the most common 1M among sALL patients were breast (17.9%) and prostate (17.4%). Patients with any 1M were at increased risk of developing sALL (SIR 1.76, 95% CI 1.58–1.95, P < 0.001). Hematological‐1M sites had significantly higher SIRs (hematological‐SIR 7.35; solid‐SIR 1.33; P < 0.001). We observed a significant increase in sALL incidence after a 1M and a significantly worse 5‐year survival with different demographic characteristics from 1ALL. There is a need to define appropriate screening methods for patients surviving their primary cancer.

AimsThere is limited information regarding the clinicopathological and immunohistochemical characteristics of gastric pyloric gland adenomas (PGAs).Methods and resultsSixty‐seven cases of gastric PGA from 57 patients were analysed. PGAs occurred with similar frequency in men and women (47.4 and 52.6%, respectively), with a mean age of 66 years. Most presented in the gastric body/fundus (67.2%). Fifteen cases (22.4%) developed against a background of autoimmune gastritis (AIG), whereas normal mucosa was seen in 35.8%. Only 16.4% (11 cases) developed in patients with a genetic predisposition, most commonly familial adenomatous polyposis. Low‐grade lesions had a mean size of 1.5 cm, while PGAs with high‐grade dysplasia (HGD) or adenocarcinoma had a mean size of 3.5 cm (P < 0.001) and more commonly showed tubulovillous architecture (50.0 versus 25.6% in low‐grade dysplasia; P = 0.040). Most PGAs (61.2%) co‐expressed mucin (MUC)5AC and MUC6 (mixed type), which was associated significantly with HGD or adenocarcinoma (P = 0.013). AIG was also associated with HGD (P = 0.027), but genetic predisposition did not correlate with the grade of dysplasia (P = 0.793). The recurrence rate of PGA was similar for high‐ (11.8%) and low‐grade lesions (7.4%) (P = 0.624).ConclusionsThe risk of HGD increases with the size of PGA, tubulovillous architecture and the presence of AIG as well as mixed immunophenotype. As the overall local recurrence rate is less than 10%, PGAs may be treated conservatively, but they should be excised completely if possible, particularly if they are large or show high‐grade features.

To address the role of atrial natriuretic factor (ANF) in hypothyroidism in the control of cardiorenal-endocrine function during volume loading, the relationships between atrial pressure, ANF, the renin-angiotensin-aldosterone system, and renal hemodynamic and excretory function were examined during and after acute 10% body wt saline volume infusion in pentobarbital-anesthetized hypothyroid dogs (n = 8). Hormonal changes before and after thyroidectomy were also evaluated. Four to 6 wk after thyroidectomy, ANF decreased and arginine vasopressin (AVP) and plasma renin activity (PRA) increased. Acute saline volume expansion caused an increase in ANF and decreases in AVP and PRA. Atrial pressure increased throughout volume expansion. Despite the absence of an increase in glomerular filtration rate (GFR) during volume expansion, urinary sodium excretion increased due to a marked rise in fractional excretion of sodium. These studies demonstrate that in hypothyroidism 1) ANF is decreased; 2) despite the decrease in basal ANF, increases in atrial pressure can stimulate relase of ANF; 3) despite the absence of an increase in GFR during volume expansion, fractional excretion of sodium increases associated with an increase in ANF; and 4) a lack of an increase in GFR during volume expansion is not related to an inability to increase ANF.

Objective Distal femoral varus osteotomy (DFVO) is an effective treatment for unloading valgus knee malalignment; however, there is limited evidence on the ability for patients to return to athletics following this procedure. The purpose of this study is to report the functional outcomes and rate of return to sport for athletes that underwent DFVO. Design A consecutive series of athletes that had undergone DFVO were retrospectively reviewed. Radiographs were assessed to determine preoperative and postoperative alignment. Institutional registries were used to collect preoperative and postoperative Marx Activity Scale, International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form scores, and return to sport. Results Thirteen patients (8 males, 5 females) with a mean age of 24 years (range 17-35 years) and a mean follow-up of 43 months (range 24-74 months) were included in the study. Six patients underwent medial closing wedge DFVO versus 7 patients who underwent lateral opening wedge DFVO. Nine of 13 had concomitant chondral, meniscal, or ligamentous procedures performed. The mean alignment correction was 8° (range 5°-13°). All patients were able to successfully return to sport at a mean of 11 months (range 9-13 months). Furthermore, all 13 patients demonstrated an improvement in both Marx Activity Scale (4-11; P < 0.01) and IKDC scores (53-89; P < 0.01) after surgery. Conclusions Correction of valgus knee malalignment through DFVO—either medial closing wedge or lateral opening wedge—can reliably result in improvement in function and return to sport. Concomitant chondral, meniscal, and ligamentous pathology should be addressed.