Acute Graft-vs.-Host Disease-Associated Endothelial Activation Is Prevented by Defibrotide.

Angiogenesis and endothelial activation and dysfunction have been associated with acute graft-vs.-host disease (aGVHD), pointing to the endothelium as a potential target for pharmacological intervention. Defibrotide (DF) is a drug with an endothelium-protective effect that has been approved for the treatment of veno-occlusive disease/sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation.

Prehabilitation programs and ERAS protocols in gynecological oncology: a comprehensive review.

Purpose: The "Enhanced recovery after surgery" (ERAS) concept has been continuously developed for many surgical disciplines. Shorter length of stay (LOS) and associated cost savings have been achieved without an increase in the complication or readmission rate. Current guidelines helped to support an increasing standardisation of care.

Electrochemical characterization of novel Ag-based brazing alloys for dental applications.

Objective: Taking into account that clinical data have proven the decomposition of Ag brazing alloys used in the production of orthodontic appliances the aim of this study was to develop new Ag based soldering alloys free of Cu and Zn.

Methods: Four commercially available Ag brazing alloys were selected and their electrochemical properties were compared to the following experimental alloys: Ag12Ga, Ag10Ga5Sn, Ag20In and Ag7Sn. 112 disk shape specimens were prepared for each alloy and their electrochemical properties were evaluated by Open Circuit Potential (OCP), linear sweep voltametry (LSV), cyclic polarization (CP) and electrochemical impedance spectroscopy (EIS) in a NaCl 0.

Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study.

Background: Advanced recurrent ovarian cancer (ROC) is the leading cause of gynecologic cancer-related death in developed countries and new treatments are needed. Previous studies of immune checkpoint blockade showed low objective response rates (ORR) in ROC with no identified predictive biomarker.

Patients And Methods: This phase II study of pembrolizumab (NCT02674061) examined two patient cohorts with ROC: cohort A received one to three prior lines of treatment with a platinum-free interval (PFI) or treatment-free interval (TFI) between 3 and 12 months and cohort B received four to six prior lines with a PFI/TFI of ≥3 months.

A GCIG international survey: clinical practice patterns of sentinel lymph node biopsies in cervical cancer.

Purpose: To evaluate the practice patterns among centers and physicians worldwide regarding sentinel lymph node biopsies (SLNB) in cervical cancer (CC) patients.

Method: A validated 35-item questionnaire regarding SLNB in CC supported by the Gynecologic Cancer Intergroup (GCIG), and sponsored by the North-Eastern German Society of Gynaecologic-Oncology (NOGGO) was sent to all major gynecological cancer societies across the globe for further distribution from October 2015 and continued for a period of 7 months.

Results: One hundred and sixty-one institutions from around the world participated.

Effectiveness of Prenatal Intervention on the Outcome of Diseases That Have a Postnatal Urological Impact.

We reviewed the literature addressing outcomes of fetal intervention of conditions that require post-natal urological management including lower urinary tract obstruction, hydrometrocolpos, congenital adrenal hyperplasia, and myelomeningocele. Despite several decades of fetal intervention for these conditions, benefits remain elusive in part because of the enormous difficulty of conducting prospective randomized studies. In this review, we reached the following conclusions: Prenatal intervention in lower urinary tract obstruction (LUTO) improves survival in the worst cases by improving pulmonary function and it may be advantageous for renal function, particularly in patients with adverse urine parameters.

Surgical Management of Neurogenic Sphincter Incompetence in Children.

We report on the results of a literature review regarding the indications and results of operations to increase bladder outlet resistance to achieve dryness in children with neurogenic sphincter incompetence (NSBD). The relative advantages and disadvantages of injection of bulking agents, periurethral slings, bladder neck reconfiguration, artificial sphincters, and bladder neck closure based on a literature review and our combined clinical experience are discussed. Based on this review and our experience, we propose that periurethral injection of bulking agents is not justified as a primary treatment.

Stigma of Mental Illness in Germans and Turkish Immigrants in Germany: The Effect of Causal Beliefs.

Stigma poses an additional burden for people suffering from mental illness, one that often impairs their social participation and can prevent them from seeking adequate help. It is therefore crucial to understand how stigma develops in order to counteract it by setting up effective evidence-based anti-stigma interventions. The present study examines the effect of causal beliefs on stigmatizing behavioral intentions, namely people's desire to distance themselves from persons with mental illness.

Metabolomic prostate cancer fields in HRMAS MRS-profiled histologically benign tissue vary with cancer status and distance from cancer.

In this article, we review the state of the field of high resolution magic angle spinning MRS (HRMAS MRS)-based cancer metabolomics since its beginning in 2004; discuss the concept of cancer metabolomic fields, where metabolomic profiles measured from histologically benign tissues reflect patient cancer status; and report our HRMAS MRS metabolomic results, which characterize metabolomic fields in prostatectomy-removed cancerous prostates. Three-dimensional mapping of cancer lesions throughout each prostate enabled multiple benign tissue samples per organ to be classified based on distance from and extent of the closest cancer lesion as well as the Gleason score (GS) of the entire prostate. Cross-validated partial least squares-discriminant analysis separations were achieved between cancer and benign tissue, and between cancer tissue from prostates with high (≥4 + 3) and low (≤3 + 4) GS.

Deletion in mice of X-linked, Brugada syndrome- and atrial fibrillation-associated Kcne5 augments ventricular K currents and predisposes to ventricular arrhythmia.

KCNE5 is an X-linked gene encoding KCNE5, an ancillary subunit to voltage-gated potassium (K) channels. Human KCNE5 mutations are associated with atrial fibrillation (AF)- and Brugada syndrome (BrS)-induced cardiac arrhythmias that can arise from increased potassium current in cardiomyocytes. Seeking to establish underlying molecular mechanisms, we created and studied Kcne5 knockout ( Kcne5) mice.

Is there a role for HIPEC in ovarian cancer?

Hyperthermic intraperitoneal chemotherapy (HIPEC) is promoted by some as a standard treatment for peritoneal carcinomatosis of epithelial ovarian cancer (EOC) and other tumor entities, despite lack of robust data supporting this. Publicly available evidence addressing the value of HIPEC in EOC is rather inconclusive, revealing contradictory and inconsistent results while some studies even report harm to the patients from a higher morbidity. On this ground, we cannot recommend the implementation and use of HIPEC outside of a randomized clinical trial setting.

Safety and dose modification for patients receiving niraparib.

Background: Niraparib is a poly(ADP-ribose) polymerase inhibitor approved in the USA and Europe for maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In the pivotal ENGOT-OV16/NOVA trial, the dose reduction rate due to treatment-emergent adverse event (TEAE) was 68.9%, and the discontinuation rate due to TEAE was 14.

Metabolomic Prediction of Human Prostate Cancer Aggressiveness: Magnetic Resonance Spectroscopy of Histologically Benign Tissue.

Prostate cancer alters cellular metabolism through events potentially preceding cancer morphological formation. Magnetic resonance spectroscopy (MRS)-based metabolomics of histologically-benign tissues from cancerous prostates can predict disease aggressiveness, offering clinically-translatable prognostic information. This retrospective study of 185 patients (2002-2009) included prostate tissues from prostatectomies (n = 365), benign prostatic hyperplasia (BPH) (n = 15), and biopsy cores from cancer-negative patients (n = 14).

HOXA4/HOXB3 gene expression signature as a biomarker of recurrence in patients with high-grade serous ovarian cancer following primary cytoreductive surgery and first-line adjuvant chemotherapy.

Objectives: Aberrant homeobox (HOX) gene expression is reported in high-grade serous ovarian carcinoma (HGSOC), however, its prognostic significance remains unclear.

Methods: HOX genes associated with progression-free survival (PFS) in a discovery cohort of primary HGSOC samples with RNA sequencing data, and those previously reported to be associated with clinical outcomes, were selected for qPCR testing in an independent training cohort of primary HGSOC samples (n=71). A prognostic model for PFS was developed using univariate and multivariate Cox regression.

Prostate cancer diagnosis and characterization with mass spectrometry imaging.

Background: Prostate cancer (PCa), the most common cancer and second leading cause of cancer death in American men, presents the clinical challenge of distinguishing between indolent and aggressive tumors for proper treatment. PCa presents significant alterations in metabolic pathways that can potentially be measured using techniques like mass spectrometry (MS) or MS imaging (MSI) and used to characterize PCa aggressiveness. MS quantifies metabolomic, proteomic, and lipidomic profiles of biological systems that can be further visualized for their spatial distributions through MSI.

An improved nerve-sparing radical hysterectomy technique for cervical cancer using the paravesico-vaginal space as a new surgical landmark.

Bladder dysfunction remains a major postoperative challenge for early stage cervical cancer patients. The present prospective phase 2 trial in patients with stage IB1 and IIA1 cervical cancer follows up on our previous, unpublished work describing a new surgical landmark, the paravesico-vaginal space. We describe a novel nerve-sparing radical hysterectomy (NSRH) approach to treat early stage cervical cancer without compromising local control rate or survival.

Applications of high-resolution magic angle spinning MRS in biomedical studies II-Human diseases.

High-resolution magic angle spinning (HRMAS) MRS is a powerful method for gaining insight into the physiological and pathological processes of cellular metabolism. Given its ability to obtain high-resolution spectra of non-liquid biological samples, while preserving tissue architecture for subsequent histopathological analysis, the technique has become invaluable for biochemical and biomedical studies. Using HRMAS MRS, alterations in measured metabolites, metabolic ratios, and metabolomic profiles present the possibility to improve identification and prognostication of various diseases and decipher the metabolomic impact of drug therapies.

Incidence and Oncological Implications of Previously Undetected Tumor Multicentricity Following Pancreaticoduodenectomy for Pancreatic Adenocarcinoma in Patients Undergoing Salvage Pancreatectomy.

Background: The risk for multicentricity of pancreatic adenocarcinoma remains unclear and the question whether pancreaticoduodenectomy represents sufficient oncological treatment for patients with ductal adenocarcinoma of the head of the pancreas needs further investigation.

Patients And Methods: Clinicopathological data of patients who underwent pancreaticoduodenectomy for pancreatic adenocarcinoma between 2005 and 2015 were assessed and the incidence of tumor multicentricity among patients who required salvage pancreatectomy within 90 postoperative days was evaluated.

Results: Pancreaticoduodenectomy was performed in 1,005 patients.

Antimicrobial Effects of Mastic Extract Against Oral and Periodontal Pathogens.

Background: Various antimicrobial agents are widely used in the therapy of oral inflammatory diseases. However, their side effects and the appearance of drug resistance justify research on natural antimicrobial agents to target oral pathogens that are safe for the host. In the present study, antimicrobial properties of mastic extract on commensal and pathogenic oral bacteria, as well as its possible cytotoxic effect toward cells of epithelial and mesenchymal origin, were evaluated and compared with the common antimicrobial agents hydrogen peroxide (HO) and chlorhexidine digluconate (CHX).

Laryngeal pacing for bilateral vocal fold paralysis: Voice and respiratory aspects.

Objective: To evaluate the effects of neurostimulation with the laryngeal pacemaker (LP) system in patients with bilateral vocal fold paralysis (BVFP) in terms of voice quality and respiratory function.

Study Design: Feasibility study, first-in-human, single-arm, open-label, prospective, multicenter study with group-sequential design and 6-month follow-up period, as described in details in our previous publication.

Methods: Nine symptomatic BVFP subjects were unilaterally implanted with the LP system at three study sites in Germany and Austria.

Expression of aldehyde dehydrogenase family 1 member A1 and high mobility group box 1 in oropharyngeal squamous cell carcinoma in association with survival time.

Despite the development of novel multimodal treatment combinations in advanced oropharyngeal squamous cell carcinoma (OSCC), outcomes remain poor. The identification of specifically validated biomarkers is required to understand the underlying molecular mechanisms, to evaluate treatment efficiency and to develop novel therapeutic targets. The present study, therefore, examined the presence of aldehyde dehydrogenase family 1 member A1 (ALDH1A1) and high mobility group box 1 (HMGB1) expression in primary OSCC and analyzed the impact on survival time.