Wnt4, Wnt6 and ß-catenin expression in human placental tissue - is there a link with first trimester miscarriage? Results from a pilot study.

BACKGROUND: Demystifying the events around early pregnancy is challenging. A wide network of mediators and signaling cascades orchestrate the processes of implantation and trophoblast proliferation. Dysregulation of these pathways could be implicated in early pregnancy loss. There is accumulating evidence around the role of Wnt pathway in implantation and early pregnancy. The purpose of this study was to explore alterations in the expression of Wnt4, Wnt6 and ß-catenin in placental tissue obtained from human first trimester euploid miscarriages versus normally developing early pregnancies. METHODS: The study group consisted of first trimester miscarriages (early embryonic demises and incomplete miscarriages) and the control group of social terminations of pregnancy (TOPs). The placental mRNA expression of Wnt4, Wnt6 and ß-catenin was studied using reverse transcription PCR and real time PCR. Only euploid conceptions were included in the analysis. RESULTS: Wnt4 expression was significantly increased in placental tissue from first trimester miscarriages versus controls (p = 0.003). No significant difference was documented in the expression of Wnt6 (p = 0.286) and ß-catenin (p = 0.793). There was a 5.1fold increase in Wnt4 expression for early embryonic demises versus TOPs and a 7.6fold increase for incomplete miscarriages versus TOPs - no significant difference between the two subgroups of miscarriage (p = 0.533). CONCLUSIONS: This is, to our knowledge, the first study demonstrating significant alteration of Wnt4 expression in human placental tissue, from failed early pregnancies compared to normal controls. Undoubtedly, a more profound study is needed to confirm these preliminary findings and explore Wnt mediators as potential targets for strategies to predict and prevent miscarriage.

The prevalence and relevance of adrenal masses in patients with sporadic gastroenteropancreatic neuroendocrine tumours (GEP-NET).

OBJECTIVE: The widespread application of abdominal computerized tomography (CT) imaging has revealed that 0.98-4.0% of individuals harbour adrenal lesions (incidentalomas). There is, however, paucity of information regarding the prevalence of adrenal lesions in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETS). Purpose of this study was to estimate the prevalence of adrenal lesions in patients with GEP-NETS and identify their radiological features and clinical significance. DESIGN: The prevalence of adrenal lesions was estimated retrospectively in 438 patients with GEP-NETS who underwent abdominal imaging. Secretory status and changes in size were documented during subsequent follow-up. MEN-1 patients and ectopic ACTH-secreting tumours were excluded. RESULTS: Adrenal lesions were detected in 32 (8.4%) of 383 patients included. The majority (22 patients - 69%) were located at the left adrenal gland and the mean size was 23.6 mm. In two patients, one with a well and another with a poorly differentiated tumour, clinicopathological features suggested adrenal metastases. During a mean follow-up period of 69.5 months, no subsequent growth of any adrenal lesion was observed. Endocrine evaluation documented subclinical glucocorticoid hypersecretion in 4 cases (14%). The presence of adrenal lesions did not correlate to distant metastases, however, they were observed more frequently in patients with G3 tumours. CONCLUSION: The prevalence of adrenal lesions in patients with GEP-NETs was found to be higher than the general population and mostly represent benign adrenal adenomas (except patients with G3 tumours). Nevertheless, individualized assessment of imaging characteristics should be still considered.

Comparative evaluation of three commercial identification systems using common and rare bloodstream yeast isolates.

The commercial yeast identification systems API ID32C, Auxacolor, and Vitek were evaluated using 251 molecularly identified bloodstream isolates and 2 reference strains, representing a total of 35 species (6 common and 29 rare). Correct identification rates were higher for common species (Auxacolor, 95%; API ID32C, 94%; Vitek, 92%) than for rare species (Auxacolor, 43%; API ID32C, 56%; Vitek, 64%). All systems performed equally among the former, and Vitek performed best among the latter.

Risk factors and consequences of incidental parathyroidectomy during thyroidectomy.

The objectives of this retrospective study were to investigate the incidence, risk factors, and clinical significance of incidental parathyroidectomy during thyroidectomy. In this study, there were 315 patients who underwent thyroidectomy between 1996 and 2006. All the operations were performed by a single experienced surgeon (J.S.). Pathology reports on all specimens were reviewed and information regarding patient demographics, diagnosis, operative details, and postoperative complications were collected. A total of 315 thyroidectomies were performed: 101 total thyroidectomies (32.1%) and 214 subtotal thyroidectomies (67.9%). Two hundred and eighty patients were operated on for benign disease (88.9%) and 35 for malignant disease (11.1%). Incidental parathyroidectomy was identified in 32 cases (10.2%). Preoperative diagnosis of malignant disease (P = 0.009) and duration of the disease (P = 0.001) were significant predictors of incidental parathyroidectomy. Incidental parathyroidectomy was significantly correlated with postoperative hypoparathyroidism (P = 0.03). Transient postoperative hypoparathyroidism occurred in 18 cases (6%) and permanent in three cases (1%). The duration of the disease was the sole significant predictor of postoperative hypoparathyroidism (P < 0.001). Incidental parathyroidectomy seems to be the result of the use of extensive surgical procedures. The preoperative diagnosis of malignant disease and the delay of the operation, which leads to a more advanced thyroid disease, make the use of extensive surgical procedures necessary.

Optic neuropathy following radiotherapy for Cushing's disease: case report and literature review.

Radiation-induced optic neuropathy is a rare adverse effect of radiotherapy applied for the treatment of pituitary adenomas. We report a patient with a recurrent adrenocorticotrophin secreting pituitary adenoma who received external beam irradiation after failing surgical and medical therapy. Sixteen months after radiotherapy, the patient was presented with declining visual acuity, and radiation-induced optic neuropathy was diagnosed. Despite treatment with glucocorticoids and hyperbaric oxygen, her vision did not improve. The pathophysiology, prevention and treatment of radiation-induced optic neuropathy, including the efficacy of hyperbaric oxygen therapy are reviewed.

Ultralong administration of gonadotropin-releasing hormone agonists before in vitro fertilization improves fertilization rate but not clinical pregnancy rate in women with mild endometriosis: a prospective, randomized, controlled trial.

OBJECTIVE: To evaluate the effects of gonadotropin-releasing hormone agonists (GnRH-a) on fertility in women with mild endometriosis who are undergoing in vitro fertilization and embryo transfer (IVF-ET) procedures. DESIGN: Prospective, randomized, controlled trial. SETTING: Three tertiary university hospitals. PATIENT(S): Four hundred infertile women with mild endometriosis, documented with laparoscopy, undergoing IVF and 200 women with tubal factor infertility. INTERVENTION(S): Administration of GnRH-a for 3 months before an IVF attempt (group A, n = 200) or IVF without GnRH-a (group B, n = 200). MAIN OUTCOME MEASURE(S): Follicular fluid (FF) levels of tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-8, and IL-1 receptor antagonist; fertilization rate (FR), implantation rate (IR), quality of embryos, and clinical pregnancy rate (PR). RESULT(S): Women who received GnRH-a had a statistically significantly reduced concentration of FF cytokines compared with women who did not receive this regimen. Women in group B had a reduced FR (61.7; 95% CI, 59.20-64.20) compared with the women in group A (72.7; 95% CI, 70.50-74.90) and compared with the women with tubal factor infertility (74.7; 95% CI, 72.00-77.24). The embryo quality, IR, and clinical PR showed no statistically significant improvement in the women of group A compared with group B. CONCLUSION(S): Women who received GnRH-a for 3 months had a lower concentration of FF cytokines. These women had also a higher FR than the women who did not receive GnRH-a. However, the IR, embryo quality, and clinical PR showed no statistically significant difference when comparing the two groups. CLINICALTRIALS. GOV ID: NCT01269125.

Effectiveness and safety of high-dose tigecycline-containing regimens for the treatment of severe bacterial infections.

Here we review the effectiveness and safety of high-dose tigecycline (200mg daily). A systematic search was performed in PubMed and Scopus databases as well as of abstracts presented at scientific conferences. Eight studies (263 patients; 58% critically ill) were included, comprising one randomised controlled trial (RCT), four non-randomised cohorts and three case reports. Klebsiella pneumoniae was the most commonly isolated pathogen (reported in seven studies). In the RCT, response in the clinically evaluable patients was 85.0% (17/20) in the 100mg every 12h (q12h) group and 69.6% (16/23) in the 75mg q12h group (P=0.4). More episodes of diarrhoea, treatment-related nausea and vomiting developed in the high-dose group (14.3% vs. 2.8%, 8.6% vs. 2.8% and 5.7% vs. 2.8%, respectively; P>0.05 for all comparisons). Three (8.6%) and 7 (19.6%) patients died in the 200mg and 150mg daily dose groups, respectively. The cohort studies enrolled patients with severe infections, including ventilator-associated pneumonia and complicated intra-abdominal infections. Mortality with high-dose tigecycline (100mg q12h) in the cohort studies ranged from 8.3% to 26%; mortality in the low-dose groups (50mg q12h) ranged from 8% to 61% and depended on the severity of the underlying infection. There are limited available data regarding the effectiveness and safety of high-dose tigecycline. Most of the data come from critically ill patients with difficult-to-treat infections. Pharmacokinetic/pharmacodynamic properties of tigecycline suggest that high-dose regimens may be more effective than low-dose regimens. Candidates for administration of high-dose tigecycline should be also defined.

Antineutrophil cytoplasmic antibodies testing in a large cohort of unselected greek patients.

Objective. To retrospectively evaluate ANCA testing in a cohort of unselected Greek in- and outpatients. Methods. In 10803 consecutive serum samples, ANCA were tested by indirect immunofluorescence (IIF) and ELISA. ELISA in inpatients was performed only on IIF positive sera. Results. Low prevalence (6.0%) of IIF positive samples was observed. Among these samples, 63.5% presented perinuclear (p-ANCA), 9.3% cytoplasmic (c-ANCA) and 27.2% atypical (x-ANCA) pattern. 16.1% of p-ANCA were antimyeloperoxidase (anti-MPO) positive, whereas 68.3% of c-ANCA were antiproteinase-3 (anti-PR3) positive. Only 17 IIF negative outpatients' samples were ELISA positive. ANCA-associated vasculitides (AAV), connective tissue disorders and gastrointestinal disorders represented 20.5%, 23.9%, and 21.2% of positive results, respectively. AAV patients exhibited higher rates of MPO/PR3 specificity compared to non-AAV (93.8% versus 8%). Conclusions. This first paper on Greek patients supports that screening for ANCA by IIF and confirming positive results by ELISA minimize laboratory charges without sacrificing diagnostic accuracy.

Wound dehiscence: is still a problem in the 21th century: a retrospective study.

BACKGROUND: The aim of this study was to evaluate the risk factors of wound dehiscence and determine which of them can be reverted. METHODS: We retrospectively analyzed 3500 laparotomies. Age over 75 years, diagnosis of cancer, chronic obstructive pulmonary disease, malnutrition, sepsis, obesity, anemia, diabetes, use of steroids, tobacco use and previous administration of chemotherapy or radiotherapy were identified as risk factors RESULTS: Fifteen of these patients developed wound dehiscence. Emergency laparotomy was performed in 9 of these patients. Patients who had more than 7 risk factors died. CONCLUSION: It is important for the surgeon to know that wound healing demands oxygen consumption, normoglycemia and absence of toxic or septic factors, which reduces collagen synthesis and oxidative killing mechanisms of neutrophils. Also the type of abdominal closure may plays an important role. The tension free closure is recommended and a continuous closure is preferable. Preoperative assessment so as to identify and remove, if possible, these risk factors is essential, in order to minimize the incidence of wound dehiscence, which has a high death rate.