Stapled hemorrhoidopexy: “mucosectomy or not only mucosectomy, this is the problem”

Introduction: Stapled hemorrhoidopexy was originally defined as a rectal mucosectomy. The aims of our retrospective, single-center study were to demonstrate if the excised specimen comprises only the mucosa or more wall rectal layers and if the latter excision should be considered a technical mistake with an increase in complications. Materials and Methods: We histopathologically analyzed surgical samples from patients who underwent stapled hemorrhoidopexy performed between 2014 and 2019. Patients were divided into three groups, according to the stapler used: Group A (single PPH®), Group B (double PPH®), and Group C (CPH34 HVTM). We evaluated the actual wall layers included in the stapled rectal ring. For every specimen, we reconstructed the history of the corresponding patient and the incidence of complications. Results: Of the 137 histological slides available, 13 were only mucosectomies (9.5%), and 124 presented also the submucosa and muscularis propria (90.5%)−50/58 patients in Group A, 28/28 in Group B, and 46/51 in Group C. No statistically significant difference in the rate of complications was found when stratifying patients according to the thickness of the resection [mucosectomy (M) or “full thickness” (FT)]. Discussion: Stapled hemorrhoidopexy is not a simple mucosectomy but a resection of the rectal wall with almost all its layers. This concept defines the entity of the surgical procedure and excludes a direct correlation with an increased rate of complications

Retrospective evaluation and SEEG trajectory analysis for interactive multi-trajectory planner assistant

Purpose: Focal epilepsy is a neurological disease that can be surgically treated by removing area of the brain generating the seizures. The stereotactic electroencephalography (SEEG) procedure allows patient brain activity to be recorded in order to localize the onset of seizures through the placement of intracranial electrodes. The planning phase can be cumbersome and very time consuming, and no quantitative information is provided to neurosurgeons regarding the safety and efficacy of their trajectories. In this work, we present a novel architecture specifically designed to ease the SEEG trajectory planning using the 3D Slicer platform as a basis. Methods: Trajectories are automatically optimized following criteria like vessel distance and insertion angle. Multi-trajectory optimization and conflict resolution are optimized through a selective brute force approach based on a conflict graph construction. Additionally, electrode-specific optimization constraints can be defined, and an advanced verification module allows neurosurgeons to evaluate the feasibility of the trajectory. Results: A retrospective evaluation was performed using manually planned trajectories on 20 patients: the planning algorithm optimized and improved trajectories in 98% of cases. We were able to resolve and optimize the remaining 2% by applying electrode-specific constraints based on manual planning values. In addition, we found that the global parameters used discards 68% of the manual planned trajectories, even when they represent a safe clinical choice. Conclusions: Our approach improved manual planned trajectories in 98% of cases in terms of quantitative indexes, even when applying more conservative criteria with respect to actual clinical practice. The improved multi-trajectory strategy overcomes the previous work limitations and allows electrode optimization within a tolerable time span

Myocardial infarction with nonobstructive coronary arteries: from pathophysiology to therapeutic strategies

: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a heterogeneous group of clinical entities characterized by clinical evidence of acute myocardial infarction (AMI) with normal or near-normal coronary arteries on coronary angiography (stenosis < 50%) and without an over the alternative diagnosis for the acute presentation. Its prevalence ranges from 6% to 11% among all patients with AMI, with a predominance of young, nonwhite females with fewer traditional risks than those with an obstructive coronary artery disease (MI-CAD). MINOCA can be due to either epicardial causes such as rupture or fissuring of unstable nonobstructive atherosclerotic plaque, coronary artery spasm, spontaneous coronary dissection and cardioembolism in-situ or microvascular causes. Besides, also type-2 AMI due to supply-demand mismatch and Takotsubo syndrome must be considered as a possible MINOCA cause. Because of the complex etiology and a limited amount of evidence, there is still some confusion around the management and treatment of these patients. Therefore, the key focus of this condition is to identify the underlying individual mechanisms to achieve patient-specific treatments. Clinical history, electrocardiogram, echocardiography, and coronary angiography represent the first-level diagnostic investigations, but coronary imaging with intravascular ultrasound and optical coherent tomography, coronary physiology testing, and cardiac magnetic resonance imaging offer additional information to understand the underlying cause of MINOCA. Although the prognosis is slightly better compared with MI-CAD patients, MINOCA is not always benign and depends on the etiopathology. This review analyzes all possible pathophysiological mechanisms that could lead to MINOCA and provides the most specific and appropriate therapeutic approach in each scenario

Degassing and Cycling of Mercury at Nisyros Volcano (Greece)

Nisyros Island (Greece) is an active volcano hosting a high-enthalpy geothermal system. During June 2013, an extensive survey on Hg concentrations in different matrices (fumarolic fluids, atmosphere, soils and plants) was carried out at Lakki Plain, an intra-caldera area affected by widespread soil and fumarolic degassing. Concentrations of gaseous elemental mercury (GEM), H2S and CO2, were simultaneously measured in both the fumarolic emissions and the atmosphere around them. At the same time, 130 samples of top soils and 31 samples of plants (Cistus Creticus and Salvifolius and Erica Arborea and Manipuliflora) were collected for Hg analysis. Mercury concentrations in fumarolic gases ranged from 10,500 to 46,300 ng/m3, while Hg concentrations in the air ranged from high background values in the Lakki Plain caldera (10-36 ng/m3) up to 7100 ng/m3 in the fumarolic areas. Outside the caldera, the concentrations were relatively low (2-5 ng/m3). The positive correlation with both CO2 and H2S in air highlighted the importance of hydrothermal gases as carrier for GEM. On the other hand, soil Hg concentrations (0.023-13.7 µg/g) showed no significant correlations with CO2 and H2S in the soil gases, whereas it showed a positive correlation with total S content and an inverse one with the soil-pH, evidencing the complexity of the processes involving Hg carried by hydrothermal gases while passing through the soil. Total Hg concentrations in plant leaves (0.010-0.112 μg/g) had no direct correlation with soil Hg, with Cistus leaves containing higher values of Hg respect to Erica. Even though GEM concentrations in air within the caldera are sometimes orders of magnitude above the global background, they should not be considered dangerous to human health. Values exceeding the WHO guideline value of 1000 ng/m3 are very rare (<0.1%) and only found very close to the main fumarolic vents, where the access to tourists is prohibited.PublishedID 47835146A. Geochimica per l'ambiente e geologia medicaJCR Journa

Integration of bovine herpesvirus 4 genome into cultured persistently infected host cell genome

Persistent infection of macrophages with bovine herpesvirus 4 (BoHV-4) has been proposed to play a secondary causal role, along with bacterial infection, in bovine post-partum metritis. Mechanisms of maintenance of BoHV-4 persistent infection are not understood. We previously generated in vitro models of BoHV-4 persistent infection in human rhadomyosarcoma and bovine macrophage cell lines by drug selection of cells infected with BoHV-4 carrying a drug-resistance marker, and demonstrated circular episomal BoHV-4 genomes. In the present study, we used fluorescent in situ hybridization (FISH) to demonstrate BoHV-4 genomes also integrated into the genomes of these persistently infected cells

Rapid biolayer interferometry measurements of urinary CXCL9 to detect cellular infiltrates noninvasively after kidney transplantation

Introduction: measuring the chemokine CXCL9 in urine by enzyme-linked immunosorbent assay (ELISA) can diagnose acute cellular rejection (ACR) noninvasively after kidney transplantation, but the required 12- to 24-hour turnaround time is not ideal for rapid, clinical decision-making. Methods: we developed a biolayer interferometry (BLI)−based assay to rapidly measure urinary CXCL9 in 200 pg/ml in subjects with ACR and ≤100 pg/ml in subjects with stable kidney function without cellular infiltrates. In samples obtained after treatment for ACR, BLI CXCL9 measurements detected biopsy-proven intragraft infiltrates despite treatment-induced reduction in serum creatinine. Discussion: together, our proof-of-principle results demonstrate that BLI-based urinary CXCL9 detection has potential as a point-of-care noninvasive biomarker to diagnose and guide therapy for ACR in kidney transplantation recipients

A Comprehensive Phenotypic and Functional Immune Analysis Unravels Circulating Anti-Phospholipase A2 Receptor Antibody Secreting Cells in Membranous Nephropathy Patients

Introduction: Primary membranous nephropathy (MN) is characterized by the presence of antipodocyte antibodies, but studies describing phenotypic and functional abnormalities in circulating lymphocytes are limited. Methods: We analyzed 68 different B- and T-cell subsets using flow cytometry in 30 MN patients (before initiating immunosuppression) compared with 31 patients with non-immune-mediated chronic kidney disease (CKD) and 12 healthy individuals. We also measured 19 serum cytokines in MN patients and in healthy controls. Lastly, we quantified the ex vivo production of phospholipase A2 receptor (PLA2R)-specific IgG by plasmablasts (measuring antibodies in culture supernatants and by the newly developed FluoroSpot assay [AutoImmun Diagnostika, Strasberg, Germany]) and assessed the circulating antibody repertoire by phage immunoprecipitation sequencing (PhIP-Seq). Results: After adjusting for multiple testing, plasma cells and regulatory B cells (BREG) were significantly higher (P < 0.05) in MN patients compared with both control groups. The percentages of circulating plasma cells correlated with serum anti-PLA2R antibody levels (P = 0.042) and were associated with disease activity. Ex vivo-expanded PLA2R-specific IgG-producing plasmablasts generated from circulating PLA2R-specific memory B cells (mBCs) correlated with serum anti-PLA2R IgG antibodies (P < 0.001) in MN patients. Tumor necrosis factor-alpha (TNF-alpha) was the only significantly increased cytokine in MN patients (P < 0.05), whereas there was no significant difference across study groups in the autoantibody and antiviral antibody repertoire. Conclusion: This extensive phenotypic and functional immune characterization shows that autoreactive plasma cells are present in the circulation of MN patients, providing a new therapeutic target and a candidate biomarker of disease activity

In vitro apoptotic effects of farnesyltransferase blockade in acute myeloid leukemia cells

Farnesyltransferase inhibitors (FTIs) are a class of oral anti-cancer drugs currently tested in phase I-II clinical trials for treatment of hematological malignancies. The in vitro effects of various FTIs (alpha-hydroxyfarnesylphosphonic acid, manumycin-A and SCH66336) were tested on CD34+ KG1a cell line and in primary acute myeloid leukemia (AML) cells from 64 patients. By cell viability and clonogeneic methylcellulose assays, FTIs showed a significant inhibitory activity in CD34+ KG1a and primary bone marrow (BM) leukemic cells from 56% of AML patients. FTIs also induced activation of caspase-3 and Fas-independent apoptosis, confirmed by the finding that inhibition of caspase-8 was not associated with the rescue of FTItreated cells. We concluded that other cellular events induced by FTIs may trigger activation of caspase-3 and subsequent apoptosis, but the expression of proapoptotic molecules, as Bcl-2 and Bcl-XL, and antiapoptotic, as Bcl-X(s), were not modified by FTIs. By contrast, expression of inducible nitric oxide synthase (iNOS) was increased in FTI-treated AML cells. Our results suggest a very complex mechanism of action of FTIs that require more studies for a better clinical use of the drugs alone or in combination in the treatment of hematological malignancies