Citations

Objective: To report a single institutional series of high-grade neuroendocrine carcinoma of the larynx (NCL), a very rare yet aggressive tumor. To review the management of NCL, including discussion of clinical behavior, treatment outcome, and prognosis. Method: A retrospective chart review of high-grade laryngeal neuroendocrine carcinomas at a single institution, including small- and large-cell neuroendocrine carcinomas. A total of 8 patients with high-grade NCL treated at our institution from 1992 to 2014 were identified. Results: The median age at diagnosis was 65.5 years (range, 43-80). Five patients were male. Two patients had a known smoking history. Primary tumor location was supraglottic in 7 patients and glottic in 1 patient. Primary treatment consisted of surgery alone (3 patients), radiotherapy alone (1 patient), combination of chemotherapy and radiotherapy (1 patient), and surgery followed by postoperative chemoradiotherapy (3 patients). Locoregional recurrence followed by distant metastasis occurred in 6 patients. Median overall survival was 44.0 months (95% CI, 3-62.0). Conclusion: High-grade NCL is a rare diagnosis. Compared to well- and moderately differentiated NCL, high-grade NCL has a far more aggressive clinical course and associated with a worse prognosis. To our knowledge, this is the largest series of patients with high-grade NCL treated at a single institution. Prompt diagnosis and multimodality therapy including elective neck dissection may improve survival.

Study Design Retrospective matched cohort analysis. Objective The majority of the literature on venous thromboembolism (VTE) after spine surgery is limited to studies of thoracolumbar surgery. Less is known regarding the incidence of VTE and associated risk factors following cervical spine surgery. Methods A total of 5,405 patients at our institution underwent cervical diskectomy, laminectomy, corpectomy, laminoplasty, or fusion between 1995 and 2012; 85 of the 5,405 patients (1.57%) suffered either a DVT (55) or pulmonary embolus (51) within 30 days postoperatively. The cases were matched 1:2 to controls based on age, sex, and date of surgery. Data regarding multiple perioperative factors, demographics, and comorbidities was collected. Results Several risk factors were identified for VTE. Significant medical comorbidities included chronic venous insufficiency (odds ratio [OR] = 3.40), atrial fibrillation (OR = 2.69), obesity (OR = 2.67), and ischemic heart disease (OR = 2.18). Staged surgery (OR = 28.0), paralysis (OR = 19.0), combined approach (OR = 7.46), surgery for infection (OR = 18.5), surgery for trauma (OR = 11.1), comorbid traumatic injuries (OR > 10), oncologic procedures (OR = 5.2), use of iliac crest autograft (OR = 4.16), two or more surgical levels (OR = 3.48), blood loss > 300 mL (OR = 1.66), and length of stay 5 days or greater (OR = 3.47) were all found to be risk factors for VTE ( p < 0.05) in univariate analysis. Multivariate analysis found staged surgery (OR = 35.7), paralysis (OR = 7.86), and nonelective surgery (OR = 6.29) to be independent risk factors for VTE. Conclusions Although the incidence of VTE following cervical spine surgery is low, we identified several risk factors that may be predictive. More aggressive approaches to prophylaxis and surveillance in certain patient populations may be warranted.

SummaryObjectiveBrain regions are localized for resection during epilepsy surgery based on rare seizures observed during a short period of intracranial electroencephalography (iEEG) monitoring. Interictal epileptiform bursts, which are more prevalent than seizures, may provide complementary information to aid in epilepsy evaluation. In this study, we leverage a long‐term iEEG dataset from canines with naturally occurring epilepsy to investigate interictal bursts and their electrographic relationship to seizures.MethodsFour dogs were included in this study, each monitored previously with continuous iEEG for periods of 475.7, 329.9, 45.8, and 451.8 days, respectively, for a total of >11,000 h. Seizures and bursts were detected and validated by two board‐certified epileptologists. A published Bayesian model was applied to analyze the dynamics of interictal epileptic bursts on EEG and compare them to seizures.ResultsIn three dogs, bursts were stereotyped and found to be statistically similar to periods before or near seizure onsets. Seizures from one dog during status epilepticus were markedly different from other seizures in terms of burst similarity.SignificanceShorter epileptic bursts explored in this work have the potential to yield significant information about the distribution of epileptic events. In our data, bursts are at least an order of magnitude more prevalent than seizures and occur much more regularly. Our finding that bursts often display pronounced similarity to seizure onsets suggests that they contain relevant information about the epileptic networks from which they arise and may aide in the clinical evaluation of epilepsy in patients.

AbstractObjectivesPolycythemia vera (PV)‐related symptoms may not be adequately controlled with conventional therapy. This current analysis of the RESPONSE trial evaluated the effects of ruxolitinib compared with standard therapy on quality of life (QoL) and symptoms in patients with PV who were hydroxyurea resistant/intolerant.MethodsIn the previously reported primary analysis, ruxolitinib achieved the primary composite endpoint of hematocrit control and ≥35% reduction in spleen volume at Week 32. The current analysis evaluated patient‐reported outcomes using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 (EORTC QLQ‐C30), the Myeloproliferative Neoplasm Symptom Assessment Form (MPN‐SAF), the Pruritus Symptom Impact Scale (PSIS), and the Patient Global Impression of Change (PGIC).ResultsCompared with standard therapy, ruxolitinib was associated with greater improvements in global health status/QoL, functional subscales, and individual symptom scores of the EORTC QLQ‐C30. At Week 32, more patients in the ruxolitinib arm (44%) achieved a ≥10‐point improvement in global health status/QoL vs. standard therapy (9%). Improvements in MPN‐SAF symptom scores were consistent with improvements in EORTC QLQ‐C30, PSIS, and PGIC scores.ConclusionsRuxolitinib provides clinically relevant improvements in QoL and ameliorates symptom burden in patients with PV who are hydroxyurea resistant/intolerant.

SummaryObjectivePolycystic ovarian syndrome (PCOS) is estimated to affect up to 20% of women. PCOS is associated with insulin resistance and cardiovascular (CV) risk factors. We aimed to evaluate the impact of race/ethnicity on the prevalence of CV risk factors and subclinical predictors of CV events.DesignCross‐sectional analysis of data collected by the Dallas Heart Study, an urban, population‐based cohort oversampled for blacks.PatientsA previously described cohort of women with PCOS and control subjects of the same racial/ethnic group, matched for age and body mass index.MeasurementsHormonal and clinical measures associated with PCOS and CV risk factors.ResultsThe study included 117 women with PCOS and 204 controls. Women with PCOS had significant differences across racial/ethnic groups in the prevalence of hypertension, hypercholesterolaemia, hypertriglyceridaemia and impaired fasting glucose (P < 0·05). Controls showed significant racial/ethnic differences in the prevalence of hypertension and impaired fasting glucose (P < 0·05). The odds of hypertension were significantly greater among women with PCOS than controls after adjusting for race/ethnicity (odds ratio, 1·50 [95% CI, 1·03–2·30]; P = 0·04). However, we did not see an interaction of race/ethnicity that significantly changed CV risk factor prevalence between PCOS and controls. In addition, subclinical measures of CV disease were not different between women with PCOS vs controls, even among hypertensive women.ConclusionsRace/ethnicity affects the prevalence of CV risk factors for women with and without PCOS. However, race/ethnicity does not interact with PCOS to additionally increase CV risk factor prevalence or subclinical CV disease.

Background. Preterm Premature Rupture of Membranes (PPROM) is a major leading cause of preterm births. While the cause for PPROM remains unidentified, it is anticipated to be due to subclinical infection, since a large proportion of PPROM patients display signs of chorioamnionitis. Since subclinical infections can be facilitated by dysbiosis, our goal was to characterize the vaginal microbiome and amniotic fluid discharge upon PPROM, through latency antibiotic treatment, and until delivery, to detect the presence of pathogens, microbiota alteration, and microbial response to treatment. Methods. Enrolled subjects (15) underwent routine institutional antenatal care for PPROM, including the administration of latency antibiotics. Serial vaginal swabs were obtained from diagnosis of PPROM through delivery and the sequencing of the V3–V5 region of the 16S rRNA gene was performed for all collected samples. Results. The results show that Lactobacilli species were markedly decreased when compared to vaginal swabs collected from uncomplicated pregnancy subjects with a matched gestational time. Prevotella and Peptoniphilus were the most prevalent taxa in PPROM subjects at presentation. The vaginal microbiome of the PPROM subjects varied substantially intra- and inter-subjects. Several taxa were found to be significantly reduced during and after the antibiotic treatment: Weeksella , Lachnospira , Achromobacter , and Pediococcus . In contrast, Peptostreptococcus and Tissierellaceae ph2 displayed a significant increase after the antibiotic treatment. However, the relative abundance of Lactobacillus , Prevotella , and Peptoniphilus was not substantially impacted during the hospitalization of the PPROM subjects. The deficiency of Lactobacillus , and constancy of known pathogenic species, such as Prevotella and Peptoniphilus during and after antibiotics, highlights the persistent dysbiosis and warrants further investigation into mitigating approaches. Discussion. PPROM is responsible for one third of all preterm births. It is thought that subclinical infection is a crucial factor in the pathophysiology of PPROM because 25–40% of patients present signs of chorioamnionitis on amniocentesis. Here we sought to directly assess the bacterial content of the vagina and leaking amniotic fluid of subjects at presentation, throughout treatment and up until delivery, in order to search for common pathogens, microbiota changes, and microbial response to latency antibiotic treatment. We have found that the vaginal microbiome of PPROM subjects is highly variable and displays significant changes to treatment. However, the unchanging deficiency of Lactobacillus , and persistence of known pathogenic species, such as Prevotella and Peptoniphilus from presentation, through antibiotic treatment and up until delivery, highlights the persistent dysbiosis and warrants further investigation into mitigating approaches.

We previously reported that the cardiomyocyte-specific leucine-rich repeat containing protein (LRRC)10 has critical functions in the mammalian heart. In the present study, we tested the role of LRRC10 in the response of the heart to biomechanical stress by performing transverse aortic constriction on Lrrc10-null ( Lrrc10−/−) mice. Mild pressure overload induced severe cardiac dysfunction and ventricular dilation in Lrrc10−/−mice compared with control mice. In addition to dilation and cardiomyopathy, Lrrc10−/−mice showed a pronounced increase in heart weight with pressure overload stimulation and a more dramatic loss of cardiac ventricular performance, collectively suggesting that the absence of LRRC10 renders the heart more disease prone with greater hypertrophy and structural remodeling, although rates of cardiac fibrosis and myocyte dropout were not different from control mice. Lrrc10−/−cardiomyocytes also exhibited reduced contractility in response to β-adrenergic stimulation, consistent with loss of cardiac ventricular performance after pressure overload. We have previously shown that LRRC10 interacts with actin in the heart. Here, we show that His150of LRRC10 was required for an interaction with actin, and this interaction was reduced after pressure overload, suggesting an integral role for LRRC10 in the response of the heart to mechanical stress. Importantly, these experiments demonstrated that LRRC10 is required to maintain cardiac performance in response to pressure overload and suggest that dysregulated expression or mutation of LRRC10 may greatly sensitize human patients to more severe cardiac disease in conditions such as chronic hypertension or aortic stenosis.