Nipple Discharge: Role of Ductoscopy in Comparison with Standard Diagnostic Tests

Background: This study aims to assess the role of ductoscopy for detecting intraductal anomalies in patients with nipple discharge in comparison to conventional tests and to find an effective combination of both approaches. Materials and Methods: Prior to duct excision, ductoscopy was performed in 97 women. Histologic and all other diagnostic results were compared. Sensitivity, specificity, and efficiency were calculated for all methods. These parameters were also calculated for all possible test combinations in 12 patients who had completed all tests. Results: Breast sonography reached the highest sensitivity (64.1%) and efficiency (64%); mammography had the highest specificity (100%). The sensitivity of ductoscopy was 53.2%, its specificity 60%, and its efficiency 55.1%. Among combinations of all methods, the combination ductoscopy + galactography was the most sensitive (80%). Mammography, magnetic resonance imaging, and ductoscopy were each 100% specific. Ductoscopy was the most efficient (75%) single method. Conclusion: Ductoscopy is a valuable test for diagnosing intraductal lesions in patients with nipple discharge. It is more efficient than conventional tests in patients undergoing all tests

Association between Serum Thyroid-Stimulating Hormone Levels and Visceral Adipose Tissue: A Population-Based Study in Northeast Germany

Background: Abdominal obesity is a major driver for adverse medical conditions. While an interaction between adipose tissue and thyroid function is thought to exist, to our knowledge, no study has examined the effect of thyroid-stimulating hormone (TSH) on visceral adipose tissue (VAT) in a population-based context. Objective: We determined an association between serum TSH levels and VAT. Methods: A sample of 1,021 female and 956 male adults aged 20-79 years was drawn from registry offices in the cross-sectional, population-based Study of Health in Pomerania Trend (SHIP Trend) in Northeast Germany from 2008 to 2012. Our main exposure was serum TSH levels. Our main outcome was VAT measured using magnetic resonance imaging. The possibly mediating role of leptin on the TSH-VAT association was also assessed. Results: A total of 1,719 participants (87.9%) had serum TSH levels within the reference range. The mean volume of VAT was 5.33 liters for men and 2.83 liters for women. No association between TSH and VAT (β = 0.06, 95% CI: -0.02, 0.14) was observed, and there were no differences detected between sexes. VAT was strongly associated with leptin with a greater effect in women than in men. Leptin was strongly associated with TSH. Conclusions: No association between TSH and VAT was observed. Other biomarkers such as leptin may play a role in the relationship between thyroid function and metabolic risk

Ductoscopic Detection of Intraductal Lesions in Cases of Pathologic Nipple Discharge in Comparison with Standard Diagnostics: The German Multicenter Study

SummaryBackground: According to the literature, ductoscopy is gaining increasing importance in the diagnosis of intraductal anomalies in cases of pathologic nipple discharge. In a multicenter study, the impact of this method was assessed in comparison with that of standard diagnostics. Patients and Methods: Between 09/2006 and 05/2009, a total of 214 patients from 7 German breast centers were included. All patients underwent elective ductoscopy and subsequent ductal excision because of pathologic nipple discharge. Ductoscopy was compared with the following standard diagnostics: breast sonography, mammography, magnetic resonance imaging (MRI), galactography, cytologic nipple swab, and ductal lavage cytology. The histological and imaging results were compared and contrasted to the results obtained from the nipple swab and cytologic assessment. Results: Sonography had the highest (82.9%) sensitivity, followed by MRI (82.5%), galactography (81.3%), ductoscopy (71.2%), lavage cytology (57.8%), mammography (57.1%), and nipple swab (22.8%). Nipple swabs had the highest (85.5%) specificity, followed by lavage cytology (85.2%), ductoscopy (49.4%), galactography (44.4%), mammography (33.3%), sonography (17.9%), and MRI (11.8%). Conclusion: Currently, ductoscopy provides a direct intraoperative visualization of intraductal lesions. Sensitivity and specificity are similar to those of standard diagnostics. The technique supports selective duct excision, in contrast to the unselective technique according to Urban. Therefore, ductoscopy extends the interventional/diagnostic armamentarium

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth

Einfluss verschiedener medikamentöser Interventionen auf den perioperativen Verlauf von ACTH, Cortisol und immunreaktiven Beta-Endorphin sowie die postoperative Infektionsrate bei alkoholkranken Patienten

Alkoholkranke Patienten haben postoperativ ein 2- bis 4fach erhöhtes Infektionsrisiko und eine verlängerte intensivmedizinische Behandlungszeit. Als Ursache werden durch chronischen Alkoholkonsum und operativen Stress induzierte Veränderungen der Hypothalamus-Hypophysen-Nebennieren (HHN) Achse diskutiert. Ziel dieser Studie war es, zu klären, ob die Intervention mit niedrig dosiertem Ethanol, Morphin oder Ketoconazol im Vergleich zu Placebo einen Einfluss auf die HHN-Achse hat und ob dadurch die postoperative Infektionsrate und intensivstationäre Behandlungszeit verkürzt werden können. 64 alkoholkranke Patienten mit elektiver Tumorresektion des oberen Aerodigestivtraktes wurden in diese randomisierte, doppelblinde, kontrollierte Studie eingeschlossen. Chronisch alkoholkranke Patienten konsumierten täglich >60g Alkohol und erfüllten die DSM-IV Kriterien für Alkoholabhängigkeit oder –abusus. Die perioperative Intervention begann am Vorabend der Operation und endete am 3. postoperativen Tag. Blutproben zur Bestimmung von ACTH, beta-Endorphin und Cortisol wurden präoperativ sowie am 1., 3. und 7. postoperativen Tag entnommen. Chirurgischer Stress induzierte in der Placebo-Gruppe einen signifikanten postoperativen Anstieg von ACTH und Cortisol. Ethanol, Morphin und Ketoconazol verhinderten den postoperativen Anstieg von ACTH und Cortisol. Für den perioperativen Verlauf von beta-Endorphin gab es keine signifikanten Unterschiede. Placebo-Patienten hatten eine deutlich erhöhte postoperative Infektionsrate, die jede der Interventionen signifikant reduzierte. Zusätzlich konnte im Vergleich zu Placebo-Patienten die intensivstationäre Behandlungszeit um 9 Tage gesenkt werden. Eine prophylaktische Intervention mit niedrig dosiertem Ethanol, Morphin oder Ketoconazol verhinderte ein perioperatives Entgleisen der HHN-Achse bei alkoholkranken Patienten. Dadurch wurden die postoperative Infektionsrate und die intensivstationäre Behandlungsdauer bei diesen Patienten reduziert.Postoperative infections are 2- to 4-times more frequent in patients with alcohol use disorders with the sequel of prolonged ICU stay. Its association with an altered perioperative hypothalamic-pituitary-adrenal (HPA) axis as response to chronic alcohol consumption and surgical stress is discussed. The aim of this study was to evaluate an intervention with low-dose ethanol, morphine or ketoconazole compared to placebo on the HPA axis and the postoperative infections rate as well as the ICU stay in chronic alcoholic patients. 64 patients with alcohol use disorders undergoing elective surgery of the aerodigestive tract were included in this randomized, double-blind controlled study. Chronic alcoholic patients were defined as having a daily ethanol consumption of at least 60 g and fulfilling the DSM-IV criteria for either alcohol abuse or dependence. Perioperative intervention was started on the evening before surgery and continued for three days after surgery. Blood samples to analyze ACTH, immune reactive beta-endorphine and cortisol were obtained on the morning before intervention and continued on day 1, 3 and 7 after surgery. In the placebo group surgical stress induced a significant increase of ACTH and cortisol. Perioperative intervention with ethanol, morphin or ketoconazol decreased the postoperative ACTH and cortisol increase in these patients. Plasma immune reactive beta-endorphine levels did not differ between groups. Placebo patients had a significantly increased postoperative infections rate whereas any intervention decreased the incidence of infections. Additionally ICU stay was reduced by 9 days in each intervention group compared to placebo. Prophylactic intervention with low dose ethanol, morphine or ketoconazole prevented a postoperative alteration of the HPA axis in chronic alcoholic patients. This was associated with a decreased postoperative infections rate and decreased ICU stay in these patients