Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

The Impact of Removing the 10-Minute Bout Requirement and of Different Survey Administration Methods on National Physical Activity Estimates in Austria.

Background: Monitoring survey methods, as well as movement recommendations, evolves over time. These changes can make trend observations over time difficult. The aim of this study was to examine the differences between 2 computer-assisted survey administration methods and the effect of the omission of the 10-minute minimum bout requirement in physical activity (PA) questions on PA outcomes.

Noninvasive inter- and intrafractional motion control in ultrahypofractionated radiation therapy of prostate cancer using RayPilot HypoCath™-a substitute for gold fiducial-based IGRT?

Purpose: In ultrahypofractionated radiation concepts, managing of intrafractional motion is mandatory because tighter margins are used and random errors resulting from prostate movement are not averaged out over a large number of fractions. Noninvasive live monitoring of prostate movement is a desirable asset for LINAC-based prostate stereotactic body radiation therapy (SBRT).

Methods: We prospectively analyzed a novel live tracking device (RayPilot HypoCath™; Micropos Medical AB, Gothenburg, Sweden) where a transmitter is noninvasively positioned in the prostatic urethra using a Foley catheter in 12 patients undergoing ultrahypofractionated intensity-modulated radiation therapy (IMRT) of the prostate.

Pretreatment 18-FDG-PET/CT parameters can serve as prognostic imaging biomarkers in recurrent NSCLC patients treated with reirradiation-chemoimmunotherapy.

Background And Purpose: Our study aimed to assess whether quantitative pretreatment 18F-FDG-PET/CT parameters could predict prognostic clinical outcome of recurrent NSCLC patients who may benefit from ablative reirradiation.

Materials And Methods: Forty-eight patients with recurrent NSCLC of all UICC stages who underwent ablative thoracic reirradiation were analyzed. Twenty-nine (60%) patients received immunotherapy with or without chemotherapy in addition to reirradiation.

Human skin-resident CD8 T cells require RUNX2 and RUNX3 for induction of cytotoxicity and expression of the integrin CD49a.

The integrin CD49a marks highly cytotoxic epidermal-tissue-resident memory (T) cells, but their differentiation from circulating populations remains poorly defined. We demonstrate enrichment of RUNT family transcription-factor-binding motifs in human epidermal CD8CD103CD49a T cells, paralleled by high RUNX2 and RUNX3 protein expression. Sequencing of paired skin and blood samples revealed clonal overlap between epidermal CD8CD103CD49a T cells and circulating memory CD8CD45RACD62L T cells.

Chemo-Radio-Immunotherapy for NSCLC III: ESR/ATS Thresholds for DL Correlate with Radiation Dosimetry and Pneumonitis Rate.

Introduction: Durvalumab following chemoradiotherapy (CRT) for non-small cell lung cancer stage III has become the standard of care (SoC) in the past few years. With this regimen, 5-year overall survival (OS) has risen to 43%. Therefore, adequate pulmonary function (PF) after treatment is paramount in long-term survivors.

Protective antibodies and T cell responses to Omicron variant after the booster dose of BNT162b2 vaccine.

The high number of mutations in the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes its immune escape. We report a longitudinal analysis of 111 vaccinated individuals for their antibody levels up to 6 months after the third dose of the BNT162b2 vaccine. After the third dose, the antibody levels decline but less than after the second dose.

Carbon Monoxide Diffusing Capacity (DL) Correlates with CT Morphology after Chemo-Radio-Immunotherapy for Non-Small Cell Lung Cancer Stage III.

Introduction: Curatively intended chemo-radio-immunotherapy for non-small cell lung cancer (NSCLC) stage III may lead to post-therapeutic pulmonary function (PF) impairment. We hypothesized that the decrease in global PF corresponds to the increase in tissue density in follow-up CTs. Hence, the study aim was to correlate the dynamics in radiographic alterations to carbon monoxide diffusing capacity (DLCO) and FEV1, which may contribute to a better understanding of radiation-induced lung disease.

High Dose Thoracic Re-Irradiation and Chemo-Immunotherapy for Centrally Recurrent NSCLC.

Introduction: Thoracic re-irradiation for recurrent lung cancer dates back four decades, when the first small series on 29 patients receiving palliative doses was published. With 5-year overall survival rates of 57% in PDL-1 positive patients after primary chemo-radio-immunotherapy, the number of patients who experience loco-regional relapse will increase in the near future. In this context, centrally recurring lung tumors pose a major treatment challenge.

Hsa-miR-3651 could serve as a novel predictor for in-breast recurrence via FRMD3.

Background: MicroRNAs are small non-coding RNAs with pivotal regulatory functions in multiple cellular processes. Their significance as molecular predictors for breast cancer was demonstrated in the past 15 years. The aim of this study was to elucidate the role of hsa-miR-3651 for predicting of local control (LC) in early breast cancer.

Single-Cell Analysis Reveals Major Histocompatibility Complex II‒Expressing Keratinocytes in Pressure Ulcers with Worse Healing Outcomes.

Pressure ulcer (PU) is a chronic wound often seen in patients with spinal cord injury and other bed-bound individuals, particularly in the elderly population. Despite its association with high mortality, the pathophysiology of PU remains poorly understood. In this study, we compared single-cell transcriptomic profiles of human epidermal cells from PU wound edges with those from uninjured skin and acute wounds in healthy donors.

Dynamics of antibody response to BNT162b2 vaccine after six months: a longitudinal prospective study.

Background: SARS-CoV-2 mRNA vaccines have proven high efficacy, however, limited data exists on the duration of immune responses and their relation to age and side effects.

Methods: We studied the antibody and memory T cell responses after the two-dose BNT162b2 vaccine in 122 volunteers up to 6 months and correlated the findings with age and side effects.

Findings: We found a robust antibody response to Spike protein after the second dose.

Impact of reirradiation, chemotherapy, and immunotherapy on survival of patients with recurrent lung cancer: A single-center retrospective analysis.

Background: Given the limited curative treatment options for recurrent lung cancer patients, the aim of our retrospective study was to investigate whether these patients would benefit in terms of overall survival (OS) by adding immunotherapy to high-dose reirradiation.

Materials And Methods: Between 2013 and 2019, 47 consecutive patients with in-field tumor recurrence underwent high-dose thoracic reirradiation at our institute. Twenty patients (43%) received high-dose reirradiation only, while 27/47 (57%) additionally had systemic therapy (immunotherapy and/or chemotherapy).

IL-22 Paucity in APECED Is Associated With Mucosal and Microbial Alterations in Oral Cavity.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by recessive mutations in the gene. The hallmark of the disease is the production of highly neutralizing autoantibodies against type I interferons and IL-22. Considering the importance of IL-22 in maintaining mucosal barrier integrity and shaping its microbial community, we sought to study potential changes in the oral cavity in this model of human IL-22 paucity.

Neuronal Function and Dopamine Signaling Evolve at High Temperature in Drosophila.

Neuronal activity is temperature sensitive and affects behavioral traits important for individual fitness, such as locomotion and courtship. Yet, we do not know enough about the evolutionary response of neuronal phenotypes in new temperature environments. Here, we use long-term experimental evolution of Drosophila simulans populations exposed to novel temperature regimes.

Risk-adapted moderate hypofractionation of prostate cancer : A prospective analysis of acute toxicity, QOL and outcome in 221 patients.

Purpose: Prostate cancer (PCA) is highly heterogeneous in terms of its oncologic outcome. We therefore aimed to tailor radiation treatment to the risk status by using three different hypofractionated radiation regimen differing in applied dose, use of rectum spacer, inclusion of pelvic lymph nodes (pLN) and use of androgen deprivation therapy (ADT). Here we report on acute toxicity, quality of life (QOL) and oncologic outcome at a median follow-up of 12 months.

Rectum-spacer related acute toxicity - endoscopy results of 403 prostate cancer patients after implantation of gel or balloon spacers.

Background: Rectal spacers are used to limit dose to the anterior rectal wall in high dose external beam radiation therapy of the prostate and have been shown to reduce radiation induced toxicity. Here we report the complication rate and toxicity of the implantation procedure in a large cohort of patients who have either received a gel- or balloon-type spacer.

Methods: In total, 403 patients received rectal spacing, 264 with balloon, 139 with gel.

• Pancho trial (p53-adapted neoadjuvant chemotherapy for resectable esophageal cancer) completed-mutation rate of the marker higher than expected.

Background: In operable esophageal cancer patients, neoadjuvant therapy benefits only those who respond to the treatment. The • Pancho trial represents the first prospective randomized trial evaluating the relevance of the mark53 status for predicting the effect of two different neoadjuvant chemotherapies.

Method: Biomarker analysis was conducted using the mark53 analysis.

Exploring the surgical landscape of pancreatic neuroendocrine neoplasia in Austria: Results from the ASSO pNEN study group.

Introduction: Pancreatic neuroendocrine neoplasia (pNEN) show increasing incidence and management is complex due to biological heterogeneity. Most publications report isolated high-volume single-centre data. This Austrian multi-centre study on surgical management of pNENs provides a comprehensive real-life picture of quality indicators, recurrence-patterns, survival factors and systemic treatments.

Transjugular intrahepatic portosystemic shunts (TIPS) for the prevention of variceal re-bleeding - A two decades experience.

Background And Aims: Transjugular intrahepatic portosystemic shunts (TIPS) are used in patients with cirrhosis for the prevention of variceal rebleeding.

Methods: We retrospectively evaluated re-bleeding rate, patency, mortality, and transplant-free survival (TFS) in cirrhotic patients receiving TIPS implantation for variceal bleeding between 1994-2014.

Results: 286 patients received TIPS (n = 119 bare metal stents, n = 167 polytetrafluorethylene (PTFE)-covered stents) for prevention of variceal re-bleeding.

Bayesian and frequentist analysis of an Austrian genome-wide association study of colorectal cancer and advanced adenomas.

Most genome-wide association studies (GWAS) were analyzed using single marker tests in combination with stringent correction procedures for multiple testing. Thus, a substantial proportion of associated single nucleotide polymorphisms (SNPs) remained undetected and may account for missing heritability in complex traits. Model selection procedures present a powerful alternative to identify associated SNPs in high-dimensional settings.

IL-22 neutralizing autoantibodies impair fungal clearance in murine oropharyngeal candidiasis model.

Protection against mucocutaneous candidiasis depends on the T helper (Th)17 pathway, as gene defects affecting its integrity result in inability to clear Candida albicans infection on body surfaces. Moreover, autoantibodies neutralizing Th17 cytokines have been related to chronic candidiasis in a rare inherited disorder called autoimmune polyendocriopathy candidiasis ectodermal dystrophy (APECED) caused by mutations in autoimmune regulator (AIRE) gene. However, the direct pathogenicity of these autoantibodies has not yet been addressed.

ePTFE-TIPS vs repetitive LVP plus albumin for the treatment of refractory ascites in patients with cirrhosis.

Background & Aims: Reduction in portal pressure by self-expandable polytetrafluoroethylene (ePTFE)-covered transjugular intrahepatic portosystemic shunts (TIPS) is a treatment option for refractory ascites. Data on clinical outcomes after ePTFE-TIPS vs repetitive large-volume paracentesis (LVP) plus albumin (A) administration for the treatment of patients with refractory ascites are limited.

Methods: Retrospective comparison of ePTFE-TIPS vs LVP+A in terms of (i) control of ascites, (ii) occurrence of overt hepatic encephalopathy (HE) and (iii) transplant-free survival in cirrhotic patients with refractory ascites.