Prognosis and risk factors of early onset pneumonia in ventilated patients with Guillain–Barré syndrome

Objective Invasive mechanical ventilation is required in 30% of patients with Guillain–Barré syndrome (GBS) and is associated with pneumonia and increased mortality. Our objective was to determine the incidence, characteristics, outcomes, and risk factors of pneumonia in GBS patients receiving mechanical ventilation.Design and setting Study of a prospective database in an intensive care unit of a university hospital.Patients The study included 81 patients who required intubation for GBS. Neurological findings, vital capacity, and signs of respiratory distress were recorded at admission and at intubation. A score predicting the risk of intubation (0–4) was calculated for each patient. Pneumonia was diagnosed based on predefined criteria and retrospectively confirmed by two observers. Early-onset pneumonia was defined as pneumonia diagnosed within 5 days after intubation.Measurements and results Mean vital capacity was 57 ± 22% of predicted at admission and 33 ± 11% at intubation. Pneumonia developed in 63 patients (78%), including 48 with early-onset pneumonia. Bacteria were consistent with aspiration. Of the 63 patients with pneumonia 11 (18%) had septic shock, 6 (10%) had acute respiratory distress syndrome, and 9 (14%) died. In the univariate analysis milder weakness, a lower risk of intubation (score < 2), and time from admission to intubation longer than 2 days were associated with early-onset pneumonia. Time from admission to intubation was the only independent predictor in the multivariate logistic regression model.Conclusions Early-onset pneumonia is a common and severe complication that is related to aspiration in patients with GBS. Delaying intubation may increase the risk of early-onset pneumonia.     

Immunohistochemical expression of mismatch repair genes (hMSH2 and hMLH1) in hepatocellular carcinoma in Egypt

Egypt has the highest prevalence rate of hepatitis C virus (HCV) infection in the world. HCV contributes to the development of about 70% of hepatocellular carcinoma (HCC) cases. Understanding the molecular basis of hepatocarcinogenesis is important for planning the therapeutic regimen for HCC patients. To clarify the possible role of mismatch repair (MMR) genes in HCV-related HCC, we studied 50 HCV-related HCC specimens (28 of which were with adjacent non-cancerous cirrhotic liver tissue, ANCLT) and 30 specimens of chronic liver disease (CLD) with no evidence of HCC. All cases were examined immunohistochemically to demonstrate the protein expression of hMSH2 and hMLH1. Thirty-two (64%) and 35 (70%) of the HCC cases revealed reduced expression of hMSH2 and hMLH1, respectively. Reduced expression of both the proteins was obtained in 26 (52%) of the HCC cases. The expression of hMSH2 and hMLH1 was reduced in 53.6% and 64.3% of ANCLT cases, respectively, with no significant difference between HCC and ANCLT. All 30 specimens of CLD had preserved expression of hMSH2 and hMLH1. Multivariate analysis showed that the reduced expression of hMSH2 or hMLH1 was significantly associated with higher grades of the tumor (p = 0.002 and 0.02, respectively).The relationships of these MMR genes with other clinicopathologic factors were not significant. Reduced expression of hMSH2 and hMLH1 in both HCC and ANCLT suggests that this event occurs at early stages of HCV-related hepatocarcinogenesis. Moreover, the significant association between reduced expression of both MMR genes and poor histologic grades of the tumor claims that these proteins are involved in the process of cancer progression.     

Proposal for a modified grading system based on mitotic index and Bcl2 provides objective determination of clinical outcome for patients with breast cancer

We hypothesized that the interaction between mitotic index (M) and Bcl2 could accurately discriminate between low- and high-grade breast cancer (BC) and provide a more objective measure of clinical outcome than histological grade, especially for patients with intermediate histological grade (G2), small size or oestrogen receptor (ER)-negative cancers. A well-characterized series of 1650 BCs with long-term follow-up was subjected to immunohistochemical analysis for Bcl2. Mitotic index (M) was assessed according to Nottingham Grading System (NGS) guidelines: M1: < 10 mitoses; M2: 10-18 mitoses; M3: > 18 mitoses. Results were validated in an independent series of patients (n = 245) uniformly treated with adjuvant anthracycline-based chemotherapy. Subsequently, BCs were classified according to the combined M/Bcl2 profile and compared with NGS. Multivariate Cox regression models using validated prognostic factors demonstrated that the subgroups defined by M/Bcl2 profile remained significantly associated with patients' outcome but also performed better than lymph node status and tumour size. Incorporation of the M/Bcl2 profile into the Nottingham Prognostic Index (NPI) reclassified twice as many patients into the excellent prognosis group, potentially improving decision-making and sparing patients unneeded systemic adjuvant therapy. Patients with M2-3/Bcl2- and M3/Bcl2+ (high risk) had a two- to three-fold increased risk of recurrence when treated with either adjuvant hormone therapy or anthracycline-based chemotherapy compared with those with M1/Bcl2 ± and M2/Bcl2+ (low risk) [HR = 3.4 (2.8-5.6); p < 0.0001 and HR = 2.3 (1.2-4.3); p = 0.0009]. In conclusion, a grading system defined by mitotic counting and Bcl2 expression accurately reclassified patients with NGS-G2, small tumour size or ER-negative cancers into two groups: low risk (NGS-G1-like) versus high risk (NGS-G3-like) of BC mortality and recurrence, improving prognosis and therapeutic planning.     

Over one thousand patients with early stage endometriosis treated with the Helica Thermal Coagulator (HELICA): safety aspects

Study objective: To assess the safety of the Helica Thermal Coagulator in the laparoscopic treatment of early stage endometriosis. Design: Retrospective, observational. Settings: The Princess Royal University Hospital, The Sloane and Chelsfield Park Hospitals, Kent, UK. Patients: One thousand and sixty patients with early stage endometriosis. Results: All patients were treated laparoscopically with the Helica Thermal Coagulator; a new laparoscopic device that combines electrical energy with helium for the treatment of endometriosis. No major bladder, ureteric or bowel injuries occurred. The only complication was a perforated vagina from the cutting probe during dissection of the cul-de-sac in a patient with a vaginal endometriotic nodule. Conclusion: The Helica Thermal Coagulator is a safe device for the laparoscopic treatment of endometriosis.No financial support has been granted for this study     

Tamoxifen citrate for women with unexplained infertility

Objective To assess whether administration of tamoxifen citrate (TMX) to women with unexplained infertility is beneficial. The primary outcome was the clinical pregnancy rate.Study design In a prospective randomized trial, 66 consecutive women with unexplained infertility were recruited for the study. Thirty-six women received TMX at a 20-mg dosage and 30 women received no ovulation-induction drugs.Results Fourteen patients in the TMX group stopped taking TMX, and observations were terminated because of antiestrogenic effects. The pregnancy rate (PR) per patient and the PR per cycle were significantly decreased (P < 0.005) in the TMX group than in the spontaneous group. Kaplan–Meier tests showed that the cumulative PR in the TMX group was significantly lower than in the spontaneous group (P < 0.05). Ten of 14 patients who had stopped taking TMX became pregnant in spontaneous cycles.Conclusions Administration of tamoxifen to women with unexplained infertility is not efficacious in terms of increasing the clinical PR.     

Allergic diseases,smoking, and environmental exposure among university students in Lebanon

Introduction: Smoking habits among university students in Lebanon are not clearly identified, and studies correlating these habits to asthma and allergic diseases are lacking. The primary objective of this study is to assess asthma and allergic diseases' predictors, particularly cigarette and/or waterpipe smoking and other environmental exposures, among university students. A second objective is to evaluate the potential role of these predictors as correlates of health-related self-assessment. Methods: A cross-sectional study, using a proportionate cluster sample of 3000 Lebanese students in both public and private universities, was conducted between January 2015 and December 2015. Results: The number of smokers at home, living close to an electricity generator and exposure to sand and dust significantly increased the odds of having asthma or allergic diseases (p = 0.015; OR = 1.183; p = 0.01; OR = 2.062; p = 0.001; OR = 3.558 respectively). Having tried cigarette smoking and having an air conditioner inside the means of transportation would decrease the odds of having asthma or allergic diseases by around 68% and 56.1% respectively (p = 0.009; OR_a = 0.320; p = 0.01; OR_a = 0.439 respectively). Conclusion: Although students with asthma or allergic diseases tended to avoid all identifiable atopic risk factors, lesser known environmental factors such as living close to an electricity generator, exposure to sand and dust, and exposure to car exhaust fumes were associated with a higher risk of asthma and a decrease in health related self-assessment. Students with asthma and allergic diseases smoked cigarettes and waterpipe at similar percentages, but cigarette smokers had a lower health related self-assessment.     

The quassinoid derivative NBT-272 targets both the AKT and ERK signaling pathways in embryonal tumors

The quassinoid analogue NBT-272 has been reported to inhibit MYC, thus warranting a further effort 7to better understand its preclinical properties in models of embryonal tumors (ET), a family of childhood malignancies sharing relevant biological and genetic features such as deregulated expression of MYC oncogenes. In our study, NBT-272 displayed a strong antiproliferative activity in vitro that resulted from the combination of diverse biological effects, ranging from G(1)/S arrest of the cell cycle to apoptosis and autophagy. The compound prevented the full activation of both eukaryotic translation initiation factor 4E (eIF4E) and its binding protein 4EBP-1, regulating cap-dependent protein translation. Interestingly, all responses induced by NBT-272 in ET could be attributed to interference with 2 main proproliferative signaling pathways, that is, the AKT and the MEK/extracellular signal-regulated kinase pathways. These findings also suggested that the depleting effect of NBT-272 on MYC protein expression occurred via indirect mechanisms, rather than selective inhibition. Finally, the ability of NBT-272 to arrest tumor growth in a xenograft model of neuroblastoma plays a role in the strong antitumor activity of this compound, both in vitro and in vivo, with its potential to target cell-survival pathways that are relevant for the development and progression of ET.