Endometrial vaporization of the cervical stump employing an office hysteroscope and bipolar technology

We report the successful treatment of a 40-year-old woman with ongoing cyclical vaginal bleeding lasting 10 days after laparoscopic subtotal hysterectomy. Hysteroscopic vaporization of the endometrial stripe in the cervical stump was performed in an office setting, using a 5-mm Bettocchi double-channel operative hysteroscope armed with a bipolar electrode.     

Novel rifamycins. III. Synthesis and antibacterial activity of 3-amidino- and of 4-aminoimidazolo[4,5-c]rifamycin derivatives

A number of semisynthetic rifamycin derivatives modified at position 3 and/or 4, belonging to general structures 2 and 4 (see Scheme 1), have been obtained. The synthesis and the biological activities of the new compounds are described. Compounds 4p and 4q display very good antimycobacterial activity in mice.     

Depletion and bioavailability of imidocarb residues in sheep and goat tissues

The residual depletion of a commercial product containing imidocarb dipropionate in sheep and goat tissues was investigated. Additionally, the oral bioavailability of residues was determined in rats to evaluate the extent to which tissue imidocarb residues could be reabsorbed by consumers. Ten ewes and 5 goats were administered im with a commercial formulation containing imidocarb dipropionate (Carbesia cavalli, Shering-Ploug 121.15 mg/ml) at the single dose of 3 mg/kg bw corresponding to 2.1 mg/kg bw imidocarb base. Two sheep and 1 goat were slaughtered 15, 30, 60, 90 or 120 d after dosing and samples of muscle, injection site muscle, liver, omental and subcutaneous fat, and kidneys were collected. Samples of cerebral hemisphere, cerebellum, olfactory bulb, pineal and pituitaryglands were dissected. For the residue bioavailability study 7 groups of3 Wistar rats each, were dosed by gavage with imidocarb dipropionate standard in water (group 2, 3 and 4) or with imidocarb as a liver residue collected from prior dosed animals (group 5, 6 and 7) at 8.4. 16.8 or 33.6 microg/kg of imidocarb base respectively, for 5 d. Group I was control. All animals were sacrificed the day after the last drug administration and livers were collected. The highest drug levels in sheep and goats occurred in liver and kidney, suggesting that these tissues are targets for residues; muscle had negligible importance as storage tissue. Goats had a lower storage capability than sheep. The residue profile in sheep liver and omental fat showed a 30-d storage period to reach maximum concentrations, and suggested that imidocarb is redistributed. The high and long-lasting concentrations in brain showed its capacity to cross the blood-brain barrier and caused concern for potential neurotoxic effects. Detectable concentrations of imidocarb were not found in rat liver.     

Costimulatory Molecules and Cytotoxic T cells in Chronic Hepatitis C: Defence Mechanisms Devoted to Host Integrity or Harmful Events Favouring Liver Injury Progression? A Review

The recruitment of antigen-specific lymphocytes at liver site represents a prominent feature in patients chronically infected with hepatitis C virus (HCV). However, despite the strong and multispecific response, chronic infection leads in a significant number of cases to the development of cirrhosis and hepatocellular carcinoma. The finding that the expression of CD80 structure positively correlates with disease histological worsening points out a role for the costimulatory pathway in the progression of liver cell injury. On the other hand, the demonstration of CD95 and CD95-ligand positive cells in the context of periportal areas, a pattern which is not strictly associated to HCV tissue distribution, indicates the occurrence of either virus-infected or innocent bystander hepatocyte killing. Nonetheless, the persistence of HCV, in spite of cytotoxic T lymphocyte (CTL) liver recruitment, suggests a possible in-situ imbalance of cytotoxic activities, above all referred to perforin-granzyme-dependent necrosis.

Altogether, these findings outline that several factors might be involved in HCV-driven immunopathogenesis. Therefore, the fully clarification of these mechanisms may offer a suitable therapeutical approach for the improvement of clinical outcome in chronic hepatitis C.     

Whole gene deletion and splicing mutations expand the PINK1 genotypic spectrum

Autosomal recessive parkinsonism is a genetic condition closely resembling Parkinson disease, the only distinguishing features being an earlier age at onset and a slower disease progression. Three causative genes have been identified so far. While exon rearrangements are frequently encountered in the Parkin gene, most PINK1 mutations are represented by single nucleotide changes. We report a sporadic parkinsonian patient carrying a deletion of the entire PINK1 gene and a splice site mutation (g.15445_15467del23) which produces several aberrant mRNAs. This report expands the genotypic spectrum of PINK1 mutations, with relevant implications for molecular analysis of this gene.     

Second-line treatments for Advanced Hepatocellular Carcinoma: A Systematic Review and Bayesian Network Meta-analysis

Background & Aims

A plethora of second-line therapies have been recently introduced for hepatocellular carcinoma (HCC) treatment with promising results. A meta-analysis of second-line treatments for HCC has been performed to better tailor their use based on improved patient stratification and to identify the best available option.

Methods

Pubmed, Scopus, Web of Science, and ClinicalTrials.gov were searched for randomized controlled trials evaluating second-line treatment for advanced HCC in patients already treated with sorafenib. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS) and drug withdrawal due to adverse events. Network meta-analyses were performed considering placebo as the basis for comparison in efficacy and safety analyses. Subgroup stratification considered gender, age, sorafenib-responsiveness and drug tolerability, viral infection, macrovascular invasion, HCC extrahepatic spread, performance status, and alpha-fetoprotein levels.

Results

Fourteen phase II or III randomized controlled trials, involving 5,488 patients and 12 regimens, were included in the analysis. Regorafenib (hazard ratio (HR)?=?0.63, 95% confidence interval (CI)?=?0.50–0.79), cabozantinib (HR?=?0.76, 95% CI?=?0.63–0.92), and ramucirumab (HR?=?0.82, 95% CI?=?0.70–0.76) significantly prolonged OS compared with placebo. Cabozantinib (HR?=?0.44, 95% CI?=?0.36–0.52), regorafenib (HR?=?0.46, 95% CI?=?0.37–0.56), ramucirumab (HR?=?0.54, 95% CI?=?0.43–0.68), brivanib (HR?=?0.56, 95% CI?=?0.42–0.76), S-1 (HR?=?0.60, 95% CI?=?0.46–0.77), axitinib (HR?=?0.62, 95% CI?=?0.44–0.87), and pembrolizumab (HR?=?0.72, 95% CI?=?0.57–0.90) significantly improved PFS compared with placebo. None of the compared drugs deemed undoubtedly superior after having performed a patients’ stratification.

Conclusions

The results of this network meta-analysis suggest the use of regorafenib and cabozantinib as second-line treatments in HCC.

     

MRI can assess glenoid bone loss after shoulder luxation: inter- and intra-individual comparison with CT

Objective

Computed tomography (CT) is the gold standard for evaluating glenoid bone loss in patients with glenohumeral dislocations. The aim of this study was to verify if magnetic resonance imaging (MRI) can quantify the area of bone loss without any significant difference from CT.

Materials and methods

Twenty-three patients, who had experienced one or more post-traumatic unilateral glenohumeral dislocations, underwent MRI and CT. MR and multiplanar reconstruction CT images were acquired in the sagittal plane: the glenoid area and the area of bone loss were calculated using the PICO method. Mean values, percentages, Cohen’s kappa coefficients and Bland-Altman plots were all used to confirm the working hypothesis.

Results

The mean glenoid surface area was 575.29 mm² as measured by MRI, and 573.76 mm² as measured by CT; the calculated mean glenoid bone loss was respectively 4.38% and 4.34%. The interobserver agreement was good (k>0.81), and the coefficient of variance was 5% of the mean value using both methods. The two series of measurements were within two standard deviations of each other.

Conclusions

MRI is a valid alternative to CT for measuring glenoid bone loss in patients with glenohumeral dislocation.     

Coagulation testing before epidural analgesia at delivery: cost analysis

Backgound

The usefulness of coagulation tests performed before epidural analgesia for surgery or to alleviate labour pain is controversial. The aims of this study were: 1) to evaluate the prevalence of abnormal tests in a large cohort of healthy pregnant women and their association with epidural hematoma; 2) to assess the approach of the anesthesiologists to women with abnormal tests; 3) to evaluate the cost of performing coagulation tests before epidural analgesia in all healthy pregnant women.

Methods

Data regarding epidural analgesia, epidural hematoma, PT, APTT, fibrinogen and platelet count were extracted from medical charts.

Results

There was no case of epidural hematoma in 2546 pregnant women undergoing epidural analgesia. PT and APTT results were obtained in 2871 women; fibrinogen in 4063 women; platelet count in 5090 women. Three of them (0.1%) had a prolonged PT, 4 (0.14%) had a prolonged APTT, 27 (0.53%) had platelets ≤100 × 10⁹/L and 37 (0.91%) had plasma fibrinogen levels < 3 g/L. No further tests were requested by the anesthesiologists in these women. Only women with platelets < 80 × 10⁹/L were denied epidural analgesia. Based on the data from the literature on the frequencies of epidural hematoma after epidural analgesia, a total cost ranging from 4.5 to 40 million Euros to perform coagulation tests would be necessary to avoid one case of epidural hematoma.

Discussion

Unselected coagulation tests before epidural analgesia are not recommended, because epidural hematoma is extremely rare in healthy pregnant women and the cost of screening is not justified.     

Predicting and preventing cardiotoxicity in the era of breast cancer targeted therapies. Novel molecular tools for clinical issues

Treatment of breast cancer (BC) has changed over the last decade with the advent of targeted therapies. Whereas traditional chemotherapy was directed toward all rapidly dividing cells (cancerous or not), several new anti-cancer drugs are mainly tailored to specific genetic pathways of cancer cells.Ideally, the goal of these new therapies is to improve the management of cancer with a specific targeting of the malignant cell and fewer side effects than traditional chemotherapy. Due to the initial success of this approach, an increasing number of targeted drugs entered into clinical development. However, unanticipated side effects of the new drugs, such as cardiotoxicity and heart failure, emerged from several clinical trials. The mechanisms of cardiotoxicity due to traditional chemotherapy and the one due to new drugs seem to be inherently different. In the case of BC, available targeted therapies are probably associated with the abrogation of normal molecular pathways involved in cardiomyocytes and endothelial cells survival/proliferation. The cardiac safety profile of these new drugs asks for a careful patient monitoring and follow up.Herein we will review the cardiotoxicity of BC patients receiving antiERBB2 treatment (Trastuzumab, Lapatinib), VEGF inhibitors (Bevacizumab) and tirosin-kinase inhibitors (Sorafenib, Sunitinib). We will discuss the molecular mechanisms that underlie the risk of cardiotoxicity, and we will examine the molecular tools useful for prediction of heart failure and for identification of subgroups of BC patients more susceptible to cardiac side effects induced by targeted therapies. Attention will be paid in particular to ERBB2 gene and its polymorphisms, as well as to the possible genetic risk stratification of BC patients.Finally, we will discuss the possible clinical strategies to prevent and minimizing the cardiotoxicity of targeted therapies in BC patients, focusing in particular on new drugs combination and on the emerging role of a tight partnership between cardiologists and oncologists.     

Optimization of computed tomography (CT) arthrography of hip for the visualization of cartilage: an in vitro study

Objective

We sought to optimize the kilovoltage, tube current, and the radiation dose of computed tomographic arthrography of the hip joint using in vitro methods.

Materials and methods

A phantom was prepared using a left femoral head harvested from a patient undergoing total hip arthroplasty and packed in a condom filled with iodinated contrast. The right hip joint of a cadaver was also injected with iodinated contrast. The phantom and the cadaver were scanned using different values of peak kilovoltage (kVp) and tube current (milliamp seconds, mAs). Three different regions of interest (ROI) were drawn in the cartilage, subchondral bone plate, and intraarticular contrast. The attenuation values, contrast/noise ratio (CNR), and effective dose were calculated. Two independent observers classified the quality of the contrast-cartilage interface and the cartilage-subchondral bone plate interface as (1) diagnostic quality or (2) nondiagnostic quality.

Results

Contrast, cartilage, and subchondral bone plate attenuation values decreased at higher kVp. CNR increased with both kVp and mAs. The qualitative analysis showed that in both phantom and cadaver, at 120 kVp and 50 mAs, the contrast-cartilage and cartilage-subchondral bone plate interfaces were of diagnostic quality, with an effective dose decreased to 0.5 MSv.

Conclusions

The absolute effective dose is not directly related to the quality of images but to the specific combination of kVp and mAs used for image acquisition. The combination of 120 kVp and 50 mAs can be suggested to decrease the dose without adversely affect the visibility of cartilage and subchondral bone plate.