Editor's Choice - Peri-operative Mortality and Morbidity of Complex Abdominal Aortic Aneurysm Repair in Switzerland: A Swissvasc Report.

Objective: Complex abdominal aortic aneurysms (cAAA) pose a clinical challenge. The aim of this study was to assess the 30 day mortality and morbidity rates for open aneurysm repair (OAR) and fenestrated or branched endovascular aortic repair (F/B-EVAR), and the effect of hospital volume in patients with asymptomatic cAAA in Switzerland.

Methods: Retrospective, cohort study using data from Switzerland's national registry for vascular surgery, Swissvasc, including patients treated from 1 January 2019 to 31 December 2022.

The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell-Mediated Killing of AML Leukemic Stem Cells.

The prognosis of patients with acute myeloid leukemia (AML) is limited, especially for elderly or unfit patients not eligible for hematopoietic stem cell (HSC) transplantation. The disease is driven by leukemic stem cells (LSCs), which are characterized by clonal heterogeneity and resistance to conventional therapy. These cells are therefore believed to be a major cause of progression and relapse.

Collaboration between local nephrologists and the transplant centre ensures good outcomes in post-transplant care.

Background: Despite substantial improvements in short-term kidney allograft survival, median long-term survival remains at a standstill. It is unclear whether and to what extent a transplant centre's post-transplant care influences long-term outcomes.

Methods: We retrospectively analysed 501 single kidney transplant recipients (KTRs) who underwent transplantation between 2009 and 2018 and did not develop rejection or de novo donor-specific antibodies (dnDSA) within the first post-transplant year.

PIRCHE-II scores prove useful as a predictive biomarker among kidney transplant recipients with rejection: An analysis of indication and follow-up biopsies.

Background: Indication biopsies for deterioration of kidney allograft function often require follow-up biopsies to assess treatment response or lack of improvement. Immune-mediated injury, namely borderline rejection (BLR), T-cell mediated rejection (TCMR), or antibody-mediated rejection (ABMR), results from preformed or alloreactivity due to donor and recipient HLA-mismatches. The impact of HLA-mismatches on alloreactivity is determined by highly immunogenic HLA-epitopes.

The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.

Proteomic profiling of tear fluid as a promising non-invasive screening test for colon cancer.

Background: Current screening options for colorectal cancer (CRC) are either invasive (colonoscopy) or have lower sensitivity to identify pre-malignant lesions (fecal immunochemical test). We proposed to identify protein profiles in tears of patients with both pre-malignant polyps and CRC; these profiles could have potential as a noninvasive screening test.

Method: Colonoscopy patients were divided into "high risk" group (CRC and tubular adenomatous polyp) and "low risk" (normal and hyperplastic polyps).

Enzymatically-crosslinked gelatin hydrogels containing paenipeptin and clarithromycin against carbapenem-resistant pathogen in murine skin wound infection.

Background: The recent rise and spread of carbapenem-resistant pathogens pose an urgent threat to public health and has fueled the search for new therapies. Localized delivery of topical antibiotics is an alternative for the treatment of infected wounds caused by drug-resistant pathogens. In this study, we aimed to develop antimicrobial-loaded hydrogels for topical treatment of wound infections in a murine skin wound infection.

Paenipeptin Analogues Potentiate Clarithromycin and Rifampin against -Mediated Polymyxin-Resistant Escherichia coli .

Polymyxin resistance mediated by the gene threatens the last-resort antibiotics. Linear lipopeptide paenipeptin analogues 1 and 15 disrupted the outer membrane of Gram-negative pathogens and potentiated clarithromycin and rifampin against -positive from the FDA-CDC Antimicrobial Resistance Isolate Bank. In the presence of paenipeptin, clarithromycin and rifampin resulted in over 3-log reduction of Moreover, paenipeptin-antibiotic combinations significantly reduced in a murine thigh infection model.

Dantrolene Attenuates Cardiotoxicity of Doxorubicin Without Reducing its Antitumor Efficacy in a Breast Cancer Model.

Dysregulation of calcium homeostasis is a major mechanism of doxorubicin (DOX)-induced cardiotoxicity. Treatment with DOX causes activation of sarcoplasmic reticulum (SR) ryanodine receptor (RYR) and rapid release of Ca in the cytoplasm resulting in depression of myocardial function. The aim of this study was to examine the effect of dantrolene (DNT) a RYR blocker on both the cardiotoxicity and antitumor activity of DOX in a rat model of breast cancer.

"And I Let It All Out": Survivors' Sibling Sexual Abuse Disclosures.

There is consensus in child sexual abuse (CSA) literature with respect to the central role of the disclosure process. However, CSA disclosure is challenging for all children, those who have experienced intrafamilial abuse. In recent years, there has been growing research into sibling sexual abuse (SSA), which is a prevalent and severe, but also the least studied form of intrafamilial CSA.

Patients' and therapists' experiences of general change mechanisms during bug-in-the-eye and delayed video-based supervised cognitive-behavioral therapy. A randomized controlled trial.

Objective: This secondary analysis of a randomized controlled trial investigated whether bug-in-the-eye (BITE) supervision (live computer-based supervision during a psychotherapy session) affects the manner in which patients and therapists experience general change mechanisms (GCMs) during cognitive-behavioral therapy (CBT).

Method: A total of 23 therapists were randomized either to the BITE condition or the control condition (delayed video-based [DVB] supervision). After each session, both patients (BITE: n = 19; DVB: n = 23) and therapists (BITE: n = 11; DVB: n = 12) completed the Helping Alliance Questionnaire (HAQ) and the Bernese Post Session Report (BPSR).

Competence feedback improves CBT competence in trainee therapists: A randomized controlled pilot study.

Objective: The development and improvement of therapeutic competencies are central aims in psychotherapy training; however, little is known about which training interventions are suitable for the improvement of competencies.

Method: In the current pilot study, the efficacy of feedback regarding therapeutic competencies was investigated in cognitive behavioural therapy (CBT). Totally 19 trainee therapists and 19 patients were allocated randomly to a competence feedback group (CFG) or control group (CG).

Immunotargeted photodynamic therapy for cholesteatoma: in vitro results with anti-EGFR-coated indocyanine green nanocapsules.

Hypothesis: The objective was to test the hypothesis that immunotargeted photodynamic therapy (IT-PDT) using anti-epithelial growth factor receptor (EGFR)-coated indocyanine green (ICG) nanocapsules would selectively kill cholesteatoma-derived keratinocytes while sparing middle ear-derived mucosa cells in vitro.

Background: Rates of residual cholesteatoma caused by incomplete microsurgical removal are unacceptably high; thus, development of an adjuvant therapy to safely destroy undetected residual cholesteatoma cells would be desirable. IT-PDT is a possible means to achieve this end.

Oral glutamine reduces radiation morbidity in breast conservation surgery.

This study examined the effect of oral glutamine (Gln) on radiation injury in breast cancer patients undergoing radiation therapy. The radiation injury was evaluated using Radiation Therapy Oncology Group (RTOG) scales. Cosmesis was scored.

Increased efficacy and reduced cardiotoxicity of metronomic treatment with cyclophosphamide in rat breast cancer.

Background/aim: It has been reported that continuous low-dose (metronomic) administration of cytotoxic drugs may be better tolerated and may have greater antitumor effects than a single high-dose chemotherapy. The aim of this study was to examine the efficacy and cardiotoxicity of metronomic administration of two of the most commonly used anticancer agents, cyclophosphamide (CPA) and doxorubicin (DOX), on an experimental breast cancer of rats.

Materials And Methods: Breast tumors were induced in Fisher 344 female rats by implanting Mat B III cells.

The relationship between addiction and religion and its possible implication for care.

Spirituality is a topic of increasing interest to clinicians and researchers interested in addiction because its perceived role in the promotion of meaningfulness in the recovery from addiction. Our review of the literature evaluates different domains relative to the relation between addiction, religion, and psychiatric treatment. Spirituality as a protective or precipitating factor for substance use and as a key component of recovery will be debated.

Tamoxifen and raloxifene suppress the proliferation of estrogen receptor-negative cells through inhibition of glutamine uptake.

Purpose: Modulation of estrogen receptor (ER) plays a central role in selective estrogen receptor modulators (SERMs) molecular mechanism of action, although studies have indicated that additional, non-ER-mediated mechanisms exist. It has been suggested that the induction of oxidative stress by SERM could be one of the non-ER-mediated mechanisms held responsible for their pro-apoptotic role in ER-negative cells. Tumor cells are known for their high requirement of glutamine (Gln) that serves multiple functions within the cells, including nutritional and energy source, as well as one of the precursors for the synthesis of natural antioxidant glutathione (GSH).

Glutamine regulation of doxorubicin accumulation in hearts versus tumors in experimental rats.

Purpose: Doxorubicin (DOX), an effective antineoplastic agent is known for its cardiotoxicity attributed mainly to free radical formation. Preliminary data indicated that oral glutamine (GLN) reduced cardiac oxidative damages in experimental rats treated with DOX. This study investigated the effect of GLN on DOX accumulation in tumors and normal tissues, troponin plasma concentration and functional alternations associated with DOX-induced myocardial damage.

Oral glutamine protects against acute doxorubicin-induced cardiotoxicity of tumor-bearing rats.

Doxorubicin (DOX), a widely used anticancer drug, has a dose-dependent cardiotoxicity, attributed mainly to free radical formation. The cardiomyocyte oxidative stress occurs rapidly after DOX treatment, resulting in harmful modifications to proteins, lipids, and DNA. Previous data showed that oral l-glutamine (Gln) prevented cardiac lipid peroxidation and maintained normal cardiac glutathione (GSH) levels in DOX-treated rats.

Conductive interstitial thermal therapy (CITT) inhibits recurrence and metastasis in rabbit VX2 carcinoma model.

Purpose: To investigate the potential of conductive interstitial thermal therapy (CITT) to inhibit recurrence and metastasis in a partially resected tumour model.

Method: Fifteen New Zealand white rabbits were implanted with VX2 tumour intramuscularly in the rear thigh. Once the tumour size reached 20-25 mm in diameter, three animals were randomly selected to serve as controls, while the remaining animals were designated as the study group and treated with CITT.

Dead or alive? Autofluorescence distinguishes heat-fixed from viable cells.

Purpose: A proof-of-concept study to evaluate a new autofluorescence method to differentiate necrotic thermally fixed cells from viable tissue following thermal ablation.

Methods: A conductive interstitial thermal therapy (CITT) device was used to ablate swine mammary tissue and rabbit VX-2 carcinomas in vivo. The ablated regions and 10-mm margins were resected 24 h following treatment, embedded in HistOmer and sectioned at 3 mm.

Glutamine prevents DMBA-induced squamous cell cancer.

The etiology of oral squamous cell carcinoma has been linked to environmental carcinogens, such as activated aromatic heterocyclic radicals and epoxides. Our previous work on implantable and 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer showed that oral glutamine (GLN) inhibited tumor growth possibly through stimulation of host - and selective inhibition of tumor glutathione (GSH). This finding was associated with up-regulation of NK cell activity, decreased IGF-1 and TGF-beta in the circulation and downregulation of PI-3K/Akt antiapoptotic signaling in tumors.

Glutamine affects glutathione recycling enzymes in a DMBA-induced breast cancer model.

Malignancy depletes host glutathione (GSH) levels to increase treatment-related toxicity and increases itself to resist the treatments. Our previous studies have shown that dietary glutamine (GLN) prevented 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors through enhancing gut GSH release and reducing tumor GSH level. In addition, GSH synthesis, metabolism, and recycling are accomplished in gamma-glutamyl cycle.

Oral glutamine prevents DMBA-induced mammary carcinogenesis via upregulation of glutathione production.

Objective: Glutamine is suggested to participate in glutathione synthesis. Furthermore, there is a positive relation between glutathione level and natural killer (NK) cell activity. Previously we demonstrated that supplemental glutamine inhibited tumor growth in an implantable tumor model and 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral squamous cell carcinoma model; these reductions were associated with enhancing NK cell cytotoxicity, blood glutathione levels, and/or gut glutathione release.

Effect of glutamine on gut glutathione fractional release in the implanted tumor model.

Cancer and its treatments cause a marked depletion of glutamine (GLN). However, dietary GLN can restore this loss and improve the outcomes of the treatments. The reasons behind this need to be investigated.