A novel lineage-tracing tool reveals that hypoxic tumor cells drive tumor relapse after radiotherapy.

Purpose: Tumor hypoxia imposes a main obstacle to the efficacy of anti-cancer therapy. Understanding the cellular dynamics of individual hypoxic cells before, during and post-treatment has been hampered by the technical inability to identify and trace these cells over time.

Methods And Materials: Here, we present a novel lineage-tracing reporter for hypoxic cells based on the conditional expression of a HIF1a-CreER-UnaG biosensor that can visualize hypoxic cells in a time-dependent manner and trace the fate of hypoxic cells over time.

-Linked Metastatic Paraganglioma: A Case Report with Implications for Counseling and Follow-Up of Pathogenic Variant Carriers.

Head and neck paragangliomas are slow growing and highly vascular neuroendocrine tumors. It is currently assumed that variants exclusively cause benign and often multicentric head and neck paragangliomas. Here, we present a patient diagnosed with multiple -linked head and neck paragangliomas who in addition developed paraganglioma metastases to the lung and spine and a primary or metastatic paraganglioma in the head of the pancreas.

Dynamic Current Focusing Compared to Monopolar Stimulation in a Take-Home Trial of Cochlear Implant Users.

Objectives: This study compared the performance of a dynamic partial tripolar cochlear implant speech encoding strategy termed dynamic current focusing (DCF) to monopolar stimulation (MP) using spectro-temporal, temporal, and speech-in-noise recognition testing.

Design: DCF is a strategy that utilizes tripolar or high partial tripolar stimulation at threshold level and increases loudness by slowly widening current spread towards most comfortable level. Thirteen cochlear implant users were fitted with DCF and a non-steered MP matched on pulse rate, pulse width, and active electrodes.

Hypofractionated radiotherapy combined with targeted therapy or immunotherapy: Dutch survey on current practice, knowledge and challenges.

Introduction: With the introduction of tyrosine kinase inhibitors and systemic antibodies, including immune checkpoint inhibitors, the survival of advanced-stage cancer patients has improved for many tumor types. These patients are increasingly referred for radiotherapy, but it is unclear whether radiotherapy combined with these drugs is safe. No international guidelines exist on whether or how to combine these drugs with radiotherapy.

ATG12 deficiency results in intracellular glutamine depletion, abrogation of tumor hypoxia and a favorable prognosis in cancer.

Hypoxia is a common feature of solid tumors and is associated with increased tumor progression, resistance to therapy and increased metastasis. Hence, tumor hypoxia is a prognostic factor independent of treatment modality. To survive hypoxia, cells activate macroautophagy/autophagy.

Unexpected toxicity of CDK4/6 inhibitor palbociclib and radiotherapy.

Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors have recently been approved for the treatment of hormone receptor-positive and HER2-negative metastatic breast cancer in association with endocrine therapy in postmenopausal women. Data on the interaction of CDK4/6 inhibition and radiotherapy are scarce, but some studies show unexpected toxicity.

Cases: We report three cases of unexpected severe or prolonged soft tissue, skin, and gastrointestinal toxicity in patients treated with a combination of radiotherapy and the CDK4/6 inhibitor palbociclib.

Patient survival in severe low-flow, low-gradient aortic stenosis after aortic valve replacement or conservative management.

Background And Aim: Classical and paradoxical low-flow, low-gradient (LFLG) aortic stenosis (AS) are the most challenging subtypes of AS. The current therapeutic options are aortic valve replacement (AVR) and conservative management: AVR promotes long-term survival but is invasive, while conservative management yields a poor prognosis but is noninvasive since it uses no aortic valve replacement (noAVR). The present meta-analysis investigated the rate of survival of patients with LFLG AS undergoing either AVR or noAVR interventions.

Aortic flow below and visceral circulation during aortic counterpulsation: Evaluation of an in vitro model.

Introduction: This study aimed to test a computer-driven cardiovascular model for the evaluation of the visceral flow during intra-aortic balloon pump (IABP) assistance.

Methods: The model includes a systemic and pulmonary circulation as well as a heart contraction model. The straight polyurethane tube aorta had a single visceral while four windkessel components mimicked resistance compliance of the brachiocephalic, renal and sub-mesenteric, pulmonary, and systemic circulation.

Intra-aortic balloon pump: Looking at the other side.

Intra-aortic balloon pump has been the most commonly employed cardiac assist device in the past, although, in recent years, its use in cardiogenic shock has been questioned. The pathophysiology of the proximal part of the balloon has been well studied, whereas, hemodynamics and flow below the distal portion of the balloon have not been fully understood yet. The distal flow contains a three-wave flow pattern during diastolic balloon expansion: a flow reduction in early diastole, a backflow in mid-diastole followed by a tele-diastolic flow.

Stereotactic ablative body radiotherapy (SABR) combined with immunotherapy (L19-IL2) versus standard of care in stage IV NSCLC patients, ImmunoSABR: a multicentre, randomised controlled open-label phase II trial.

Background: About 50% of non-small cell lung cancer (NSCLC) patients have metastatic disease at initial diagnosis, which limits their treatment options and, consequently, the 5-year survival rate (15%). Immune checkpoint inhibitors (ICI), either alone or in combination with chemotherapy, have become standard of care (SOC) for most good performance status patients. However, most patients will not obtain long-term benefit and new treatment strategies are therefore needed.

Are recurrence of ischemic mitral regurgitation and left ventricular reverse remodeling after restrictive annuloplasty ring dependent?

Objective: This meta-analysis investigates MR recurrence and degree of left ventricular reverse remodeling (LVRR) in CIMR patients in mitral annuloplasty employing different ring designs.

Background: The deeper understanding of complex changes caused by chronic ischemic mitral regurgitation (CIMR) have led to new generations of rings that, by maintaining normal 3D annular geometry are supposed to enhance long-term repair durability.

Methods: A meta-analysis of all available reports in literature of MV repair through different ring design was conducted.

Synergizing systemic responses by combining immunotherapy with radiotherapy in metastatic non-small cell lung cancer: The potential of the abscopal effect.

Immunotherapy has obtained a secure place in the treatment of metastatic non-small cell lung cancer (NSCLC) and has made a great impact on prognosis of responders. Unfortunately, not all NSCLC patients derive benefit from this treatment. Several immune escape mechanisms have been postulated, explaining failure of tumor immune attack.

Biological Determinants of Chemo-Radiotherapy Response in HPV-Negative Head and Neck Cancer: A Multicentric External Validation.

Tumor markers that are related to hypoxia, proliferation, DNA damage repair and stem cell-ness, have a prognostic value in advanced stage HNSCC patients when assessed individually. Here we aimed to evaluate and validate this in a multifactorial context and assess interrelation and the combined role of these biological factors in determining chemo-radiotherapy response in HPV-negative advanced HNSCC. RNA sequencing data of pre-treatment biopsy material from 197 HPV-negative advanced stage HNSCC patients treated with definitive chemoradiotherapy was analyzed.

Effectiveness of Phantom Stimulation in Shifting the Pitch Percept in Cochlear Implant Users.

Objectives: Phantom electrode stimulation was developed for cochlear implant (CI) systems to provide a lower pitch percept by stimulating more apical regions of the cochlea, without inserting the electrode array deeper into the cochlea. Phantom stimulation involves simultaneously stimulating a primary and a compensating electrode with opposite polarity, thereby shifting the electrical field toward the apex and eliciting a lower pitch percept. The current study compared the effect sizes (in shifts of place of excitation) of multiple phantom configurations by matching the perceived pitch with phantom stimulation to that perceived with monopolar stimulation.

Papillary muscle intervention vs mitral ring annuloplasty in ischemic mitral regurgitation.

Background And Aims: The main pathophysiological factor of chronic ischemic mitral regurgitation (MR) is the outward displacement of the papillary muscles (PMs) leading to leaflet tethering. For this reason, papillary muscle intervention (PMI) in combination with mitral ring annuloplasty (MRA) has recently been introduced into clinical practice to correct this displacement, and to reduce the recurrence of regurgitation.

Methods: A meta-analysis was conducted comparing the outcomes of PMI and MRA performed in combination vs MRA performed alone, in terms of MR recurrence and left ventricular reverse remodeling (LVRR).

ACLY (ATP Citrate Lyase) Mediates Radioresistance in Head and Neck Squamous Cell Carcinomas and is a Novel Predictive Radiotherapy Biomarker.

Radiotherapy is an important treatment modality of head and neck squamous cell carcinomas (HNSCC). Multiple links have been described between the metabolic activity of tumors and their clinical outcome. Here we test the hypothesis that metabolic features determine radiosensitivity, explaining the relationship between metabolism and clinical outcome.

Superior mesenteric flow pattern during counterpulsation: is simply a shorter balloon the solution for visceral hypoperfusion?

Objectives: We studied the flow pattern in the superior mesenteric artery (SMA) during intra-aortic balloon pump support, comparing 2 intra-aortic balloons of 2 different lengths.

Methods: Sixteen Landrace pigs (mean weight 84.0 kg ± 6.

Clinical outcomes of automated anastomotic devices: A metanalysis.

Background And Aims: We investigated neurological events, graft patency, major adverse cardiovascular events (MACEs), and mortality at 1 year following coronary artery bypass grafting (CABG) surgery using automated proximal anastomotic devices (APADs) and compared the overall rates with the current literature.

Methods: A systematic review of all available reports of APADs use in the literature was conducted. Cumulative incidence and 95% confidence interval (CI) were the main statistical indexes.

Acute Hypoxia Profile is a Stronger Prognostic Factor than Chronic Hypoxia in Advanced Stage Head and Neck Cancer Patients.

Hypoxic head and neck tumors respond poorly to radiotherapy and can be identified using gene expression profiles. However, it is unknown whether treatment outcome is driven by acute or chronic hypoxia. Gene expression data of 398 head and neck cancers was collected.

Dynamic current focusing for loudness encoding in cochlear implants: a take-home trial.

This study aimed to evaluate a more energy-efficient dynamic current focussing (DCF) speech-processing strategy after long-term listening experience. In DCF, tripolar stimulation is used near the threshold and loudness is controlled by the compensation coefficient σ. A recent acute pilot study showed improved spectral-temporally modulated ripple test (SMRT) scores at low loudness levels, but battery life was reduced to 1.

Channel discrimination along all contacts of the cochlear implant electrode array and its relation to speech perception.

Objective: To test the channel discrimination of cochlear implant (CI) users along all contacts of the electrode array and assess whether this is related to speech perception.

Design: CI recipients were tested with a custom-made channel discrimination test. They were asked to distinguish a target stimulus from two reference stimuli in a three-alternative forced choice (3AFC) task.

Continuous monitoring of membrane lung carbon dioxide removal during ECMO: experimental testing of a new volumetric capnometer.

Background: Extracorporeal membrane oxygenation constitutes a complex support modality, and accurate monitoring is required. An ideal monitoring system should promptly detect ECMO malfunctions and provide real-time information to optimize the patient-machine interactions. We tested a new volumetric capnometer which enables continuous monitoring of membrane lung carbon dioxide removal (V'COML), to help in estimating the oxygenator performance, in terms of CO removal and oxygenator dead space (VDsML).

Superior mesenteric and renal flow patterns during intra-aortic counterpulsation.

New Findings: What is the central question of this study? Visceral ischaemia is one of the most feared complications during use of an intra-aortic balloon pump. Using an animal model, we measured the flows at the abdominal level directly and examined flow patterns to enable investigation of flow patterns during the use of the intra-aortic balloon pump. What is the main finding and its importance? We show that there is a significant balloon-related reduction in superior mesenteric flow in both early and mid-diastole.

Proarrhythmic proclivity of left-stellate ganglion stimulation in a canine model of drug-induced long-QT syndrome type 1.

Background: Left-stellate ganglion stimulation (LSGS) can modify regional dispersion of ventricular refractoriness, promote triggered activity, and reduce the threshold for ventricular fibrillation (VF). Sympathetic hyperactivity precipitates torsades de pointes (TdP) and VF in susceptible patients with long-QT syndrome type 1 (LQT1). We investigated the electromechanical effects of LSGS in a canine model of drug-induced LQT1, gaining novel arrhythmogenic insights.

Dynamic Current Focusing: A Novel Approach to Loudness Coding in Cochlear Implants.

Objectives: In an attempt to improve spectral resolution and speech intelligibility, several current focusing methods have been proposed to increase spatial selectivity by decreasing intracochlear current spread. For example, tripolar stimulation administers current to a central electrode and uses the two flanking electrodes as the return pathway, creating a narrower intracochlear electrical field and hence increases spectral resolution when compared with monopolar (MP) stimulation. However, more current is required, and in some patients, specifically the ones with high electrode impedances, full loudness growth cannot be supported because of compliance limits.