Development of CAR-T Therapies and Personalized Vaccines for the Treatment of Cholangiocarcinoma: Current Progress, Mechanisms of Action, and Challenges.

Cholangiocarcinoma (CCA) is a highly fatal malignancy with an increasing prevalence, a high mortality rate, poor overall survival, and limited responsiveness to conventional chemoradiotherapy. Targeted therapies addressing specific gene mutations have expanded treatment options for some patient populations. The introduction of chimeric antigen receptor-modified T-cell (CAR-T) immunotherapy and personalized vaccines have opened up a new avenue for managing various cancers.

All-cause and cause-specific mortality in patients with chronic hepatitis B and concurrent steatotic liver disease.

Background & Aims: Steatotic liver disease (SLD) is prevalent among patients with chronic hepatitis B (CHB). However, the effects of metabolic dysfunction-associated SLD (MASLD) on the long-term survival of such patients remain unknown. Accordingly, this study investigated the mortality risks in patients with CHB and concurrent SLD.

The Clinical Utility of Liver-Specific Ultrasound Contrast Agents During Hepatocellular Carcinoma Imaging.

Hepatocellular carcinoma (HCC) is the most common form of hepatic malignancy, with high mortality rates recorded globally. Early detection through clinical biomarkers, medical imaging and histological assessment followed by rapid intervention are integral for positive patient outcomes. Although contrast-enhanced computed tomography scans and magnetic resonance imaging are recognised as the reference standard for the diagnosis and staging of HCC in international guidelines, ultrasound (US) examination is recommended as a screening tool for patients at risk.

Particulate air pollution at the time of oocyte retrieval is independently associated with reduced odds of live birth in subsequent frozen embryo transfers.

Study Question: Does exposure to particulate matter (PM) air pollution prior to oocyte retrieval or subsequent frozen embryo transfer (FET) affect the odds of live birth?

Summary Answer: Live birth rates are lower when particulate matter (PM2.5 and PM10) levels are higher prior to oocyte retrieval, regardless of the conditions at the time of embryo transfer.

What Is Known Already: Exposure to air pollution is associated with adverse reproductive outcomes, including reduced fecundity and ovarian reserve, and an increased risk of infertility and pregnancy loss.

Effects of preimplantation genetic testing for aneuploidy on embryo transfer outcomes in women of advanced reproductive age with no more than three retrieved oocytes.

Objective: To evaluate whether preimplantation genetic testing for aneuploidy (PGT-A) benefits women of advanced reproductive age (≥38 years old) with a diminished ovarian reserve (not more than three retrieved oocytes).

Design: A retrospective analysis comparing two groups: (a) PGT-A group: women who chose PGT-A and subsequent single re-warmed embryo transfers and (b) non-PGT-A group: women who chose not to genetically test their embryos and underwent subsequent fresh or re-warmed embryo transfers of one to two embryos on days 3 or 5.

Subjects: Two hundred thirty patients underwent PGT-A therapy, with 49 of these individuals undergoing more than one PGT-A cycle.

A blastocyst's implantation potential is linked to its originating oocyte cohort's blastulation rate: evidence for a cohort effect.

Objective: To investigate if blastocysts originating from different follicular cohorts have variable implantation rates, adjusted for oocyte age, morphology, and/or ploidy.

Design: Retrospective cohort.

Setting: Academic center.

ANGIOTENSIN II FOR CATECHOLAMINE-RESISTANT VASODILATORY SHOCK IN PATIENTS WITH ACUTE KIDNEY INJURY: A POST HOC ANALYSIS OF THE ATHOS-3 TRIAL.

Objective: The combination of catecholamine-resistant vasodilatory shock and acute kidney injury (AKI) is associated with high morbidity and mortality. The role of angiotensin II (ANGII) in this setting is unclear. Methods: We conducted a post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS) 3 trial which assessed the effect of Intravenous ANG II or placebo in patients with refractory vasodilatory shock in 75 intensive care units across nine countries in North America, Australasia, and Europe.

F-FLT PET and Blood-based Biomarkers for Identifying Gastrointestinal Graft versus Host Disease after Allogeneic Cell Transplantation.

Purpose To determine whether fluorine 18 (F) fluorothymidine (FLT) PET imaging alone or combined with Mount Sinai Acute GVHD International Consortium (MAGIC) biomarkers could help identify subclinical gastrointestinal graft versus host disease (GI-GVHD) by day 100 following hematopoietic stem cell transplantation (HSCT). Materials and Methods F-FLT PET imaging was analyzed in a prospective pilot study (ClinicalTrials.gov identifier no.

Prognostic impact of targetable driver alterations in resected early-stage lung cancer.

Background: Apart from fusions and the common mutations, targetable molecular alterations are irrelevant for adjuvant treatment decision making in early-stage non-small cell lung cancer (NSCLC). This retrospective analysis aimed to investigate if there is a difference in recurrence-free survival in stage I-III NSCLC harboring druggable molecular alterations compared to subtypes without targetable molecular alterations.

Methods: All consecutive patients who underwent surgery with curative intent for NSCLC (stage I-III) with targetable mutations between January 2015 and December 2020 at three Austrian institutions were identified and compared with tumors without targetable molecular alterations.

Implantable continuous-flow total artificial heart for newborns and small pediatric patients: First report of working model.

Objective: The need for safe and reliable mechanical circulatory support (MCS) for smaller children with severe heart failure (HF) is well defined. More specifically, in pediatric patients with advanced congenital HF, there is no implantable total artificial heart (TAH) device available for small patients. Herein, we report the development of the infant continuous-flow total artificial heart (I-CFTAH), a fully implantable in infants and newborns.

A European expert consensus surgical technique description for robotic hepatectomy.

The robotic platform enables surgeons to operate with a similar level of freedom and control as in open surgery, while still providing the patient with the benefits of a minimally invasive approach. More centres continue to adopt robotic liver surgery however standardized training materials and consensus on the surgical technique are currently lacking. The availability of a standardized surgical protocol could benefit the further dissemination of the robotic approach while promoting safe and effective operating techniques.

Circular RNAs trigger nonsense-mediated mRNA decay.

Circular RNAs (circRNAs) are covalently closed single-stranded RNAs produced predominantly through a back-splicing process. They play regulatory roles in various biological and physiological processes; however, the molecular mechanisms by which circRNAs operate remain unclear. Herein, we demonstrate that circRNAs facilitate rapid mRNA degradation through RNA-RNA interactions between circRNAs and the 3' untranslated regions (3' UTRs) of mRNAs.

Bilateral Cochlear Implants and Bimodal Hearing: A Comparison of Quality of Life.

Background:  Despite significant advances in the field of cochlear implants (CIs), there is no widely accepted criterion for when to counsel on bilateral CIs in adults. This is partly due to conflicting findings on the advantages of bilateral CIs versus bimodal hearing (i.e.

Imaging Findings and Management Strategies for Liver Masses in Children with Predisposition Disorders: A Review by the Pediatric LI-RADS Group.

Liver masses in children with underlying systemic disease or a predisposing syndrome can be benign or malignant, ranging from focal fat to hepatocellular carcinoma (HCC). Knowledge of the underlying condition, the pathophysiologic effect on the liver, and the development of liver disease and specific liver lesions allows radiologists to guide imaging with regard to modality and frequency and give recommendations for biopsy when appropriate. In some predisposition disorders, such as Beckwith Wiedemann spectrum, familial adenomatous polyposis syndrome, and tuberous sclerosis complex, established guidelines for imaging screening exist.

The Effect of Terpinen-4-ol on Human Corneal Epithelium.

Purpose: To investigate the toxicity of terpinen-4-ol (T4O) on primary cultured human corneal epithelial cells (HCECs).

Methods: HCECs were exposed to various concentrations (0%-0.1%) of T4O for 15 minutes to 72 hours.

Diagnosing primary lateral sclerosis: a clinico-pathological study.

Background:  Primary lateral sclerosis (PLS) is a rare motor neuron disease characterized by upper motor neuron degeneration, diagnosed clinically due to the absence of a (neuropathological) gold standard. Post-mortem studies, particularly TDP-43 pathology analysis, are limited.

Methods: This study reports on 5 cases in which the diagnostic criteria for PLS were met, but in which neuropathology findings showed (partially) conflicting results.

Disseminated intravascular coagulation and cirrhotic coagulopathy: overlap and differences. The current state of knowledge. Communication from the SSC of the ISTH.

Patients with disseminated intravascular coagulation (DIC) have decreasing plasma levels of coagulation factors and platelet counts with increased levels of D-dimer. Standard laboratory tests are used clinically to diagnose DIC and quantify the severity of the disease. In patients with cirrhosis, liver-derived plasma coagulation factor levels are reduced due to decreased hepatic synthesis, further exacerbated by extravascular redistribution of these proteins, causing prolongation of routine diagnostic coagulation tests.

Reverse electrical remodelling after cardiac resynchronization therapy in a patient undergoing left bundle branch area pacing: a case report.

Background: Left bundle branch area pacing (LBBAP) has been introduced as an alternative to biventricular pacing in cardiac resynchronization therapy (CRT). Several studies describe echocardiographic reverse remodelling after LBBAP. Reverse electrical remodelling after LBBAP has not yet been described.

IL-23R is a senescence-linked circulating and tissue biomarker of aging.

Cellular senescence is an aging mechanism characterized by cell cycle arrest and a senescence-associated secretory phenotype (SASP). Preclinical studies demonstrate that senolytic drugs, which target survival pathways in senescent cells, can counteract age-associated conditions that span several organs. The comparative efficacy of distinct senolytic drugs for modifying aging and senescence biomarkers in vivo has not been demonstrated.

T cell dynamics with neoadjuvant immunotherapy in head and neck cancer.

Immune-checkpoint inhibitors (ICIs) are being tested as neoadjuvant therapies in various solid tumours, including in patients with head and neck squamous cell carcinoma (HNSCC), with promising results. Key findings thus far include that this approach is well-tolerated with favourable clinical outcomes including promising pathological response rates in initial studies. Pathological responses are likely to be increased by combining other agents with anti-PD-(L)1 antibodies.

Office-Based Serial Intralesional Steroid Injections in Benign Subglottic Stenosis-First Results.

Objective: Serial intralesional steroid injections (SILSI) are increasingly used in the treatment of idiopathic subglottic stenosis (iSGS) and auto-immune related subglottic stenosis (SGS), which are both known for their high rate of recurrences. SILSI could potentially prolong the time to re-intervention. We evaluated the effects of adjuvant SILSI in iSGS and auto-immune related SGS-patients on time to reintervention and spirometry results.

Australian parents' attitudes, perceptions and supply of alcohol to adolescents: a national cross-sectional survey.

Parental supply of alcohol to adolescents is associated with increased risk of subsequent adolescent alcohol use and harms, so identifying factors associated with parents' decision-making is critical. This study examined how parental supply is associated with attitudes toward adolescent alcohol use, perceived norms of parental supply, perceived behavioural control and perceived acceptable age to drink alcohol. A total of 1197 Australian parents with children aged 12-17 years completed an online cross-sectional survey assessing their parental supply behaviours, attitudes and perceptions in April 2022.