Complicated enterocele: timely resolution with bowel resection via a vaginal approach: case report

Background: Enterocele is an uncommon, serious condition that requires accurate and early diagnosis to prevent complications such as intestinal obstruction, incarceration, and strangulation, with consequent intestinal ischemia, necrosis, and evisceration. We report a rare case of a patient with a voluminous enterocele and initial signs of intestinal ischemia who underwent urgent vaginal surgery. Case description: An 80-year-old woman presented with a voluminous mass protruding from the vagina, associated abdominopelvic pain, a 10-day history of bowel sub-occlusion, and numerous episodes of profuse vaginal bleeding. She was diagnosed with an enterocele with early signs of complications. Owing to her advanced clinical condition and comorbidities, we opted for an urgent vaginal procedure. Intestinal loops with initial signs of ischemia were resected via a transvaginal approach, leading to good clinical outcomes. She was discharged on postoperative day 5. Conclusions: This rare case highlights a surgical emergency that was managed with transvaginal resection of the intestine. Early identification of the initial signs of complications allowed for this less invasive approach, resulting in reduced morbidity and length of hospital stay

Effects of combination of sibutramine and L-carnitine compared with sibutramine monotherapy on inflammatory parameters in diabetic patients

The aim of the study was to evaluate the effects of 12-month treatment with sibutramine plus L-carnitine compared with sibutramine alone on body weight, glycemic control, insulin resistance, and inflammatory state in type 2 diabetes mellitus patients. Two hundred fifty-four patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA(1c)] >8.0\%) in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomized to take sibutramine 10 mg plus L-carnitine 2 g or sibutramine 10 mg in monotherapy. We evaluated at baseline and after 3, 6, 9, and 12 months these parameters: body weight, body mass index, HbA(1c), fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance index, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, leptin, tumor necrosis factor-α, adiponectin, vaspin, and high-sensitivity C-reactive protein. Sibutramine plus L-carnitine gave a faster improvement of fasting plasma glucose, postprandial plasma glucose, lipid profile, leptin, tumor necrosis factor-α, and high-sensitivity C-reactive protein compared with sibutramine alone. Furthermore, there was a better improvement of body weight, HbA(1c), fasting plasma insulin, homeostasis model assessment of insulin resistance index, vaspin, and adiponectin with sibutramine plus L-carnitine compared with sibutramine alone. Sibutramine plus L-carnitine gave a better and faster improvement of all the analyzed parameters compared with sibutramine alone without giving any severe adverse effect

Localization of anatomical changes in patients during proton therapy with in-beam PET monitoring: a voxel-based morphometry approach exploiting Monte Carlo simulations

Purpose: In-beam positron emission tomography (PET) is one of the modalities that can be used for in vivo noninvasive treatment monitoring in proton therapy. Although PET monitoring has been frequently applied for this purpose, there is still no straightforward method to translate the information obtained from the PET images into easy-to-interpret information for clinical personnel. The purpose of this work is to propose a statistical method for analyzing in-beam PET monitoring images that can be used to locate, quantify, and visualize regions with possible morphological changes occurring over the course of treatment. Methods: We selected a patient treated for squamous cell carcinoma (SCC) with proton therapy, to perform multiple Monte Carlo (MC) simulations of the expected PET signal at the start of treatment, and to study how the PET signal may change along the treatment course due to morphological changes. We performed voxel-wise two-tailed statistical tests of the simulated PET images, resembling the voxel-based morphometry (VBM) method commonly used in neuroimaging data analysis, to locate regions with significant morphological changes and to quantify the change. Results: The VBM resembling method has been successfully applied to the simulated in-beam PET images, despite the fact that such images suffer from image artifacts and limited statistics. Three dimensional probability maps were obtained, that allowed to identify interfractional morphological changes and to visualize them superimposed on the computed tomography (CT) scan. In particular, the characteristic color patterns resulting from the two-tailed statistical tests lend themselves to trigger alarms in case of morphological changes along the course of treatment. Conclusions: The statistical method presented in this work is a promising method to apply to PET monitoring data to reveal interfractional morphological changes in patients, occurring over the course of treatment. Based on simulated in-beam PET treatment monitoring images, we showed that with our method it was possible to correctly identify the regions that changed. Moreover we could quantify the changes, and visualize them superimposed on the CT scan. The proposed method can possibly help clinical personnel in the replanning procedure in adaptive proton therapy treatments

In-vivo range verification analysis with in-beam PET data for patients treated with proton therapy at CNAO

Morphological changes that may arise through a treatment course are probably one of the most significant sources of range uncertainty in proton therapy. Non-invasive in-vivo treatment monitoring is useful to increase treatment quality. The INSIDE in-beam Positron Emission Tomography (PET) scanner performs in-vivo range monitoring in proton and carbon therapy treatments at the National Center of Oncological Hadrontherapy (CNAO). It is currently in a clinical trial (ID: NCT03662373) and has acquired in-beam PET data during the treatment of various patients. In this work we analyze the in-beam PET (IB-PET) data of eight patients treated with proton therapy at CNAO. The goal of the analysis is twofold. First, we assess the level of experimental fluctuations in inter-fractional range differences (sensitivity) of the INSIDE PET system by studying patients without morphological changes. Second, we use the obtained results to see whether we can observe anomalously large range variations in patients where morphological changes have occurred. The sensitivity of the INSIDE IB-PET scanner was quantified as the standard deviation of the range difference distributions observed for six patients that did not show morphological changes. Inter-fractional range variations with respect to a reference distribution were estimated using the Most-Likely-Shift (MLS) method. To establish the efficacy of this method, we made a comparison with the Beam's Eye View (BEV) method. For patients showing no morphological changes in the control CT the average range variation standard deviation was found to be 2.5 mm with the MLS method and 2.3 mm with the BEV method. On the other hand, for patients where some small anatomical changes occurred, we found larger standard deviation values. In these patients we evaluated where anomalous range differences were found and compared them with the CT. We found that the identified regions were mostly in agreement with the morphological changes seen in the CT scan

The Imaging X-ray Polarimetry Explorer (IXPE): Technical Overview

The Imaging X-ray Polarimetry Explorer (IXPE) will expand the information space for study of cosmic sources, by adding linear polarization to the properties (time, energy, and position) observed in x-ray astronomy. Selected in 2017 January as a NASA Astrophysics Small Explorer (SMEX) mission, IXPE will be launched into an equatorial orbit in 2021. The IXPE mission will provide scientifically meaningful measurements of the x-ray polarization of a few dozen sources in the 2-8 keV band, including polarization maps of several x-ray-bright extended sources and phase-resolved polarimetry of many bright pulsating x-ray sources

Post partum perineal dysfunctions: a prospectic analysis of risk factors

Background Many risk factors have been recognized to explain postpartum perineal dysfunctions such as multiparity, operative delivery, prolonged second stage of labor, epidural analgesia, perineal lacerations and fetal macrosomia. The perineal damage is correlated to pregnancy and vaginal delivery due to direct mechanic trauma on muscles the elevator ani and anal sphincter, neurologic damage of pelvic floor nerves and connective-fascial lesion of the urogenital hiatus. During pregnancy there is an excessive pressure on the anterior perineum due to the weight of the gravid uterus and the direct pressure on the urogenital hiatus. During vaginal birth, all the muscular and ligamentous structures of the pelvic floor are exposed to intense pressure and traction forces in lateral and longitudinal directions. During impingement of the presenting part, the bladder is compressed between pubic bones and the fetal head with a consequent trauma that is directly correlated with the length of the expulsion phase. Health workers must be able to recognize, prevent and treat perineal dysfunctions during and after pregnancy. The aim of our study was to evaluate different maternal, neonatal and delivery-associated risk factors and analyze the pelvic floor alterations in the puerperium compared with the perineal function before birth. Methods 106 primiparae women were enrolled, 4-5 months after delivery they underwent to an interview in order to evaluate urinary and anal incontinence, perineal pain, dyspareunia and a clinic examination of the functioning of the pelvic floor with pubococcygeus test (PC test). They also filled a questionnaire about the functioning of their pelvic floor during pregnancy. In order to obtain information about the risk factors there were considered: job, maternal age, gestational age, maternal weight before pregnancy, weight at term, maternal diseases, type of delivery (spontaneous, operative, caesarian section), episiotomy, grade of lacerations, Kristeller maneuver, type of induction (if any), length of labor, length of second stage of labor, head circumference, newborn’s weight, epidural analgesia. Results Vaginal birth correlate with lower scores at PC test, urinary incontinence that is also associated with maternal age and weight, dyspareunia and perineal pain, especially in women who had operative delivery, episiotomy and/or lacerations. Epidural analgesia seems to be protective for postpartum dyspareunia (31,8% vs 44,2%). A significant correlation has been demonstrated between newborn head circumference and weight and perineal dysfunction after delivery probably due to longer labor and increased stretching of pelvic tissues. Conclusions Our data are in line with literature and underline that urinary symptoms tends to ameliorate after delivery demonstrating that pregnancy itself is a risk factor. Moreover, we discovered that in women with perineal dysfunction in postpartum the symptoms were worse than during pregnancy. If pregnancy is a risk factor for perineal dysfunctions, delivery is a worsening factor for a pre-existing situation or the appearing of new symptoms

Evaluation of metalloproteinase 2 and 9 levels and their inhibitors in combined dyslipidemia

Purpose: To evaluate the distribution of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and their specific inhibitors in a sample of patients affected by mild dyslipidemia but not yet treated with antihyperlipidemic drugs. Methods: One hundred and sixty-eight Caucasian patients aged ? 18 yr of either sex with combined dyslipidemia and who had never previously taken lipid-lowering medications were evaluated. As a control population, we enrolled 179 Caucasian healthy subjects, aged ? 18 yr of either sex. We evaluated body mass index (BMI), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), lipoprotein(a) Lp(a), plasminogen activator inhibitor-1 (PAI-1), homocysteine (Hct), fibrinogen (Fg), high sensitivity C-reactive protein (Hs-CRP), adiponectin (ADP), MMP-2, MMP-9, tissue inhibitors of metalloproteinase-1 (TIMP-1), and tissue inhibitors of metalloproteinase-2 (TIMP-2). Results: TC, Tg, and LDL-C were higher (P < < 0.05, P < < 0.01 and P < < 0.05, respectively) in the dyslipidemic group, while HDL-C levels were lower (P < < 0.01) compared with the control group. Increases of PAI-1, Hct, Fg, and Hs-CRP (P < < 0.01, P < < 0.05, P < < 0.05, and P < < 0.05, respectively) were present in the dyslipidemic group, while ADP level was lower (P < < 0.01) in the dyslipidemic patients compared with controls. MMP-2, MMP-9, TIMP-1, and TIMP-2 levels were higher (P < < 0.0001) in the dyslipidemic group. Conclusions: Combined hyperlipidemic patients have increased levels of prothrombotic and microinflammatory parameters and higher levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 than control subjects. The prognostic importance of this observation has to be evaluated in adequately designed prospective studies

Evaluation of metalloproteinase 2 and 9 levels and their inhibitors in combined dyslipidemia

Purpose: To evaluate the distribution of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and their specific inhibitors in a sample of patients affected by mild dyslipidemia but not yet treated with antihyperlipidemic drugs. Methods: One hundred and sixty-eight Caucasian patients aged ? 18 yr of either sex with combined dyslipidemia and who had never previously taken lipid-lowering medications were evaluated. As a control population, we enrolled 179 Caucasian healthy subjects, aged ? 18 yr of either sex. We evaluated body mass index (BMI), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), lipoprotein(a) Lp(a), plasminogen activator inhibitor-1 (PAI-1), homocysteine (Hct), fibrinogen (Fg), high sensitivity C-reactive protein (Hs-CRP), adiponectin (ADP), MMP-2, MMP-9, tissue inhibitors of metalloproteinase-1 (TIMP-1), and tissue inhibitors of metalloproteinase-2 (TIMP-2). Results: TC, Tg, and LDL-C were higher (P < < 0.05, P < < 0.01 and P < < 0.05, respectively) in the dyslipidemic group, while HDL-C levels were lower (P < < 0.01) compared with the control group. Increases of PAI-1, Hct, Fg, and Hs-CRP (P < < 0.01, P < < 0.05, P < < 0.05, and P < < 0.05, respectively) were present in the dyslipidemic group, while ADP level was lower (P < < 0.01) in the dyslipidemic patients compared with controls. MMP-2, MMP-9, TIMP-1, and TIMP-2 levels were higher (P < < 0.0001) in the dyslipidemic group. Conclusions: Combined hyperlipidemic patients have increased levels of prothrombotic and microinflammatory parameters and higher levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 than control subjects. The prognostic importance of this observation has to be evaluated in adequately designed prospective studies

Lysin (K)-specific demethylase 1 inhibition enhances proteasome inhibitor response and overcomes drug resistance in multiple myeloma

Abstract Background Multiple myeloma (MM) is an incurable plasma cell malignancy, accounting for approximately 1% of all cancers. Despite recent advances in the treatment of MM, due to the introduction of proteasome inhibitors (PIs) such as bortezomib (BTZ) and carfilzomib (CFZ), relapses and disease progression remain common. Therefore, a major challenge is the development of novel therapeutic approaches to overcome drug resistance, improve patient outcomes, and broaden PIs applicability to other pathologies. Methods We performed genetic and drug screens to identify new synthetic lethal partners to PIs, and validated candidates in PI-sensitive and -resistant MM cells. We also tested best synthetic lethal interactions in other B-cell malignancies, such as mantle cell, Burkitt’s and diffuse large B-cell lymphomas. We evaluated the toxicity of combination treatments in normal peripheral blood mononuclear cells (PBMCs) and bone marrow stromal cells (BMSCs). We confirmed the combo treatment’ synergistic effects ex vivo in primary CD138+ cells from MM patients, and in different MM xenograft models. We exploited RNA-sequencing and Reverse-Phase Protein Arrays (RPPA) to investigate the molecular mechanisms of the synergy. Results We identified lysine (K)-specific demethylase 1 (LSD1) as a top candidate whose inhibition can synergize with CFZ treatment. LSD1 silencing enhanced CFZ sensitivity in both PI-resistant and -sensitive MM cells, resulting in increased tumor cell death. Several LSD1 inhibitors (SP2509, SP2577, and CC-90011) triggered synergistic cytotoxicity in combination with different PIs in MM and other B-cell neoplasms. CFZ/SP2509 treatment exhibited a favorable cytotoxicity profile toward PBMCs and BMSCs. We confirmed the clinical potential of LSD1-proteasome inhibition in primary CD138+ cells of MM patients, and in MM xenograft models, leading to the inhibition of tumor progression. DNA damage response (DDR) and proliferation machinery were the most affected pathways by CFZ/SP2509 combo treatment, responsible for the anti-tumoral effects. Conclusions The present study preclinically demonstrated that LSD1 inhibition could provide a valuable strategy to enhance PI sensitivity and overcome drug resistance in MM patients and that this combination might be exploited for the treatment of other B-cell malignancies, thus extending the therapeutic impact of the project

Simulation of evapotranspiration and yield of maize: An inter-comparison among 41 maize models

International audienceAccurate simulation of crop water use (evapotranspiration, ET) can help crop growth models to assess the likely effects of climate change on future crop productivity, as well as being an aid for irrigation scheduling for today's growers. To determine how well maize (Zea mays L.) growth models can simulate ET, an initial inter-comparison study was conducted in 2019 under the umbrella of AgMIP (Agricultural Model Inter-Comparison and Improvement Project). Herein, we present results of a second inter-comparison study of 41 maize models that was conducted using more comprehensive datasets from two additional sites - Mead, Nebraska, USA and Bushland, Texas, USA. There were 20 treatment-years with varying irrigation levels over multiple seasons at both sites. ET was measured using eddy covariance at Mead and using large weighing lysimeters at Bushland. A wide range in ET rates was simulated among the models, yet several generally were able to simulate ET rates adequately. The ensemble median values were generally close to the observations, but a few of the models sometimes performed better than the median. Many of the models that did well at simulating ET for the Mead site did poorly for drier, windy days at the Bushland site, suggesting they need to improve how they handle humidity and wind. Additional variability came from the approaches used to simulate soil water evaporation. Fortunately, several models were identified that did well at simulating soil water evaporation, canopy transpiration, biomass accumulation, and grain yield. These models were older and have been widely used, which suggests that a larger number of users have tested these models over a wider range of conditions leading to their improvement. These revelations of the better approaches are leading to model improvements and more accurate simulations of ET