Comprehensive Review of Cranial Chordomas Using National Databases in the USA.

AIMS: The management of cranial chordomas is controversial. We provide a comprehensive review of the evolving patterns of care of cranial chordomas in the USA. MATERIALS AND METHODS: We analysed the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2014 for clinical characteristics and long-term survival, and the National Surgical Quality Improvement Program (NSQIP) dataset between 2005 and 2016 for perioperative characteristics and surgical morbidity. RESULTS: In total, 936 patients were identified from the NCDB, 405 patients from SEER and 64 patients from the NSQIP. Most patients were men (56.2, 54.8 and 57.8% in NCDB, SEER and NSQIP, respectively) and White (80.9 and 83.2% in NCDB and SEER, respectively). Surgery was the preferred treatment modality (87.3% in NCDB and 86.2% in SEER). Surgery was carried out alone (41.8% in NCDB and 40.7% in SEER) or in combination with radiation (42.1% in NCDB and 45.4% in SEER). Proton therapy was the most common type of radiation (32.2% in NCDB), particularly after 2011. The median operative time, median hospital length and postoperative morbidity were significantly higher in chordoma patients compared with patients who underwent other skull-base procedures. The 5-year survival rate was 79.8% in NCDB and 76.9% in SEER. There was a trend towards longer survival in patients receiving surgery and radiation, which has been increasingly used since 2004. Patients younger than 60 years had a decreased risk of mortality. CONCLUSIONS: Our analysis reflects patterns of care in the USA. The use of surgery and radiation is increasing, with a trend towards longer survival. Surgery is complicated with long operative time, hospital stay and a higher rate of complications.

Differential neuroprotective effects of 14-3-3 proteins in models of Parkinson's disease.

14-3-3 proteins are important negative regulators of cell death pathways. Recent studies have revealed alterations in 14-3-3s in Parkinson's disease (PD) and the ability of 14-3-3s to interact with alpha-synuclein (α-syn), a protein central to PD pathophysiology. In a transgenic α-syn mouse model, we found reduced expression of 14-3-3θ, ε, and γ. These same isoforms prevent α-syn inclusion formation in an H4 neuroglioma cell model. Using dopaminergic cell lines stably overexpressing each 14-3-3 isoform, we found that overexpression of 14-3-3θ, ε, or γ led to resistance to both rotenone and 1-methyl-4-phenylpyridinium (MPP(+)), while other isoforms were not protective against both toxins. Inhibition of a single protective isoform, 14-3-3θ, by shRNA did not increase vulnerability to neurotoxic injury, but toxicity was enhanced by broad-based inhibition of 14-3-3 action with the peptide inhibitor difopein. Using a transgenic C. elegans model of PD, we confirmed the ability of both human 14-3-3θ and a C. elegans 14-3-3 homolog (ftt-2) to protect dopaminergic neurons from α-syn toxicity. Collectively, these data show a strong neuroprotective effect of enhanced 14-3-3 expression - particularly of the 14-3-3θ, ε, and γ isoforms - in multiple cellular and animal models of PD, and point to the potential value of these proteins in the development of neuroprotective therapies for human PD.

Comparison of methylene blue-directed biopsies and conventional biopsies in the detection of intestinal metaplasia and dysplasia in Barrett's esophagus: a preliminary study.

BACKGROUND: The diagnostic advantage of methylene blue (MB) chromoendoscopy in Barrett's esophagus is unclear. METHODS: Patients with columnar-lined esophagus (CLE) were enrolled into a prospective, randomized crossover trial of MB-directed biopsy versus conventional biopsy. RESULTS: Forty-seven patients (19 long-segment CLE; 28 short-segment CLE) were enrolled and underwent MB-directed biopsy. Sensitivity and specificity of MB for specialized intestinal metaplasia were 53% and 51%, respectively. Sensitivity and specificity of MB for dysplasia were 51% and 48%, respectively. Thirty-five patients (15 long-segment CLE; 20 short-segment CLE) completed the crossover trial. Relative frequencies for specialized intestinal metaplasia were 73% and 71% from MB-directed and conventional biopsy specimens, respectively (p = 0.73). Relative frequencies for dysplasia were 20% and 18% from MB-directed and conventional biopsy specimens, respectively (p = 0.65). In patients with long-segment CLE, dysplasia was diagnosed in 10 patients with MB and 7 patients with conventional biopsy methods (p = 0.25). The number of biopsy specimens per EGD was greater with MB, which may have influenced the diagnosis. Histologically, the grade of dysplasia was indefinite/low in nearly all of the dysplastic specimens. CONCLUSIONS: Results of MB-directed biopsy were similar to conventional biopsy in detecting specialized intestinal metaplasia and indefinite/low-grade dysplasia. MB was not useful in short-segment Barrett's esophagus.

Pure red cell aplasia due to parvovirus B19 in a patient treated with rituximab.

Rituximab is a chimeric monoclonal antibody directed against CD20 and used in the treatment of B-cell non-Hodgkin's lymphoma. Due to its ability to deplete B lymphocytes, rituximab can interfere with humoral immunity, causing it to be suppressed for several months after treatment. The reported case depicts a serious consequence of this effect of rituximab therapy: pure red cell aplasia resulting from chronic parvovirus B19 infection. The point of interest in this case is not only the association between rituximab therapy and pure red cell aplasia, but the diagnostic and therapeutic utility of the knowledge of parvovirus B19 as the likely etiologic link between the two. Given the known efficacy of intravenous immunoglobulin (IVIg) in the treatment of chronic parvovirus B19 infection, this therapy can cure some of these patients and successfully render most others transfusion-independent until recovery of their own humoral immune system.

Localization of chromogranin, synaptophysin, serotonin, and CXCR2 in neuroendocrine cells of the minor vestibular glands: an immunohistochemical study.

Sections of vulvar tissue containing minor vestibular glands (15 sections from 14 women with vulvar vestibulitis syndrome and six control sections from five asymptomatic women) were immunohistochemically stained with antibodies against chromogranin, synaptophysin, serotonin, and CXCR2. The degree of inflammation in vestibular tissue from women with and without vulvar vestibulitis syndrome was not significantly different. All vulvar minor vestibular glands contained neuroendocrine cells that expressed chromogranin to some degree. Only one case failed to express synaptophysin. The number of cells expressing chromogranin and synaptophysin was the same regardless of the degree of inflammation. However, moderate to severe inflammation was associated with a statistically significant increase in the number of cells expressing serotonin (p < 0.001) and CXCR2 (p < 0.02). It is concluded that neuroendocrine cells are present within minor vestibular glands of the vulva. The number of cells expressing the inflammatory mediator serotonin and CXCR2, the shared interleukin-8 receptor, are upregulated with inflammation. Chronic inflammation is a normal finding in vestibular tissue and does not serve as a histologic marker for vulvar vestibulitis.

Significance of cold intolerance in upper extremity disorders.

After upper extremity injury, pain on exposure to cold (cold sensitivity) is a significant problem. This cross-sectional observational study (1) assesses the incidence and prevalence of cold intolerance, (2) evaluates the relationship between functional status and degree of cold intolerance, and (3) correlates health-related quality of life (HRQL) with symptoms of cold intolerance. Patients in a tertiary care center completed questionnaires to document (1) cold sensitivity, (2) upper extremity pain, symptoms, and function, and (3) HRQL. Cold sensitivity was found to be associated with more functional limitations, greater pain, and reduced HRQL. As the severity of cold intolerance increased, functional limitations and pain increased and HRQL decreased. Cold intolerance has a profound effect on HRQL.

Scrotal leiomyomas with bizarre nuclei: a report of three cases.

We discuss here three cases of scrotal leiomyoma with bizarre nuclei. The patients, ranging in age from 44 to 58 years, presented with painless scrotal masses that were clinically diagnosed as cysts. Clinical follow-up, available for two of the patients, revealed no evidence of local recurrence or distant metastasis 5 years after resection. The tumors were well circumscribed and ranged from 2 to 3 cm in maximal diameter. They were characterized by interlacing fascicles of spindle-shaped cells with pleomorphic nuclei. Nuclei were large and multilobulated with hyperchromatic chromatin and macronucleoli. Multinucleated tumor cells were infrequent. Intranuclear invagination of eosinophilic globules of cytoplasm produced pseudonucleoli. There was no mitotic activity. Immunohistochemically, the tumor cells expressed vimentin, desmin, smooth muscle actin, and muscle-specific actin, but not cytokeratin, neurofilament, or glial fibrillary acidic protein. In contrast to scrotal leiomyosarcomas, scrotal leiomyomas with bizarre nuclei are not hypercellular, and they lack mitotic activity.

Physician management of patients with heart failure and normal versus decreased left ventricular systolic function. Council on Geriatric Cardiology.

A questionnaire was administered to a random sample of family practitioners, internists, cardiologists, and geriatricians to examine the current management of heart failure patients with preserved versus reduced left ventricular systolic function. In patients with preserved systolic function, electrocardiogram at rest, chest x-ray, echocardiography, digitalis, angiotensin-converting enzyme inhibitors, and restriction of dietary sodium and physical activity are used less often, whereas calcium channel blockers and beta blockers are given more often than to patients with reduced systolic function.

The Postmenopausal Estrogen/Progestin Interventions Study: primary outcomes in adherent women.

OBJECTIVE: To assess the efficacy of unopposed estrogen, and three estrogen/progestin regimens on selected heart disease risk factors among adherent women and to contrast those results with efficacy among all women in the PEPI study. DESIGN: A 3-year, multicenter, randomized, double-blinded, placebo-controlled clinical trial. PARTICIPANTS: A total of 847 healthy postmenopausal women aged 45 to 64 years of age with no known contraindication to hormone therapy, who attended their 36 month clinical visit. INTERVENTION: Participants were randomized in equal numbers to one of the following treatments: (1) placebo; (2) conjugated equine estrogen (CEE) 0.625 mg daily; (3) CEE 0.625 daily plus medroxyprogesterone acetate (MPA) 10 mg, days 1-12; (4) CEE 0.625 daily plus MPA 2.5 mg daily; or (5) CEE 0.625 daily plus micronized progesterone (MP) 200 mg, days 1-12. ANALYSIS: Analyses are based on adherent women, where adherence is defined as taking at least 80% of pills at each 6-month visit. RESULTS: Adherence rates were high in all groups except women with a uterus assigned to unopposed CEE. The difference in HDL-C levels resulting from the CEE vs. CEE+MP was approximately three times larger than in the intent-to-treat analyses, reaching statistical significance (P < 0.05). In each active treatment, LDL-C decreased 10-15%. Triglycerides increased 15-20% in each opposed CEE arm and over 25% in the CEE only arm; this difference was not statistically significant. Fibrinogen increased by 7% among placebo adherers, but decreased or remained fairly stable among the active arm adherers. Systolic blood pressure increased 3-5% in all treatment arms. Women adherent to the CEE+MPA arms had twice the increase of 2 h glucose levels as women adherent to CEE only, or CEE+MP (8-9% vs. 3-4%). Two-hour insulin levels decreased 3-12% for all arms. The patterns of change for fibrinogen, SBP, 2 h glucose and insulin were similar to those from the intent-to-treat analyses. CONCLUSIONS: In analyses limited to adherent women, all active treatments, compared to placebo, continued to have similar and favorable effects on LDL-cholesterol and fibrinogen and no significant effects on blood pressure or insulin levels. Given the overall high adherence rates in PEPI, the results are similar to the intent-to-treat analyses, as expected. Only the trend of HDL-C to have a larger increase in the CEE only arm (in the intent-to-treat analyses) gained statistical significance in analyses restricted to adherers.

CML blast crisis resulting in biliary obstruction following BMT.

Allogeneic BMT is the treatment of choice for various hematologic malignancies. Despite careful patient scrutiny, a large number of patients experience significant morbidity and mortality due to procedure-related toxicity. Hepatobiliary toxicity presenting as biliary cholestasis, due to the preparative regimen (ie venoocclusive disease), supportive pharmaceuticals, and/or GVHD have been implicated. We report a unique cause of cholestasis in a patient undergoing BMT for CML. The cholestasis was found to be secondary to relapsed leukemia, which resulted in a granulocytic sarcoma obstructing the biliary ductal system.