Hydroxychloroquine in combination with platinum doublet chemotherapy as first-line treatment for extensive-stage small cell lung cancer (Study 15): A randomised phase II multicentre trial.

Background: Most patients with small-cell lung cancer (SCLC) present with extensive-stage (ES) disease and have a poor prognosis despite achieving high initial response rates to platinum-based doublet chemotherapy. This study evaluated whether adding hydroxychloroquine (HCQ) to chemotherapy could improve outcomes.

Methods: This was a randomised multicentre phase II trial.

Imaging NRF2 activation in non-small cell lung cancer with positron emission tomography.

Mutations in the NRF2-KEAP1 pathway are common in non-small cell lung cancer (NSCLC) and confer broad-spectrum therapeutic resistance, leading to poor outcomes. Currently, there is no means to non-invasively identify NRF2 activation in living subjects. Here, we show that positron emission tomography imaging with the system x radiotracer, [F]FSPG, provides a sensitive and specific marker of NRF2 activation in orthotopic, patient-derived, and genetically engineered mouse models of NSCLC.

Delphi-Based Global Consensus on Adopting Endothelial Keratoplasty: An Endothelial Keratoplasty Learners Group Initiative.

Purpose: To identify areas of consensus among experts on the performance of endothelial keratoplasty by using a modified Delphi approach, to help create a framework for novice surgeons to adopt these procedures.

Methods: Thirty-one international experts in endothelial keratoplasty participated. Two rounds of electronic survey were followed by a hybrid, virtual meeting.

Chronic Inflammation Offers Hints About Viable Therapeutic Targets for Preeclampsia and Potentially Related Offspring Sequelae.

The combination of hypertension with systemic inflammation during pregnancy is a hallmark of preeclampsia, but both processes also convey dynamic information about its antecedents and correlates (e.g., fetal growth restriction) and potentially related offspring sequelae.

Serum Folate Concentrations in Exclusively Breastfed Preterm Infants Who Received No Supplementary Oral Folic Acid After Discharge: A Prospective Cohort Study.

Adequate folate intake is required in preterm infants for rapid growth and development, but there is little evidence to back recommendations. We aimed to assess folate status in preterm infants at discharge and in early infancy, according to exposure to folate sources, particularly in those exclusively/predominantly breastfed. A prospective, multicenter, observational cohort study was conducted in the UK, involving 45 preterm infants <33 weeks' gestational age (GA) exclusively/predominantly fed human milk when approaching NICU (Neonatal Intensive Care Unit) discharge.

Rationale and strategies for improving glycaemic control in diabetic patients undergoing cardiac surgery: a narrative review.

Background And Objective: The global prevalence of diabetes mellitus has markedly risen in recent years. Consequently, there has been a rise in the number of patients with diabetes undergoing cardiac surgery. Despite the existence of national and international guidelines to improve surgical outcomes in patients with diabetes, perioperative diabetes management optimisation remains inadequate resulting in these patients experiencing increased rates of surgical morbidity and mortality.

Treatment strategies for limited-stage small cell carcinoma of the esophagus: evidence from a Chinese multicenter cohort study and the American SEER database.

Background: The rare incidence of small cell carcinoma of the esophagus (SCCE) makes prospective studies difficult to conduct, the efficacy of existing standard treatment regimens for SCCE is therefore highly controversial. This study aimed to explore differences in the efficacy of three different treatment regimens [upfront surgery, neoadjuvant chemotherapy (NCT), and chemoradiotherapy (CRT)] in patients with limited-stage SCCE (LS-SCCE).

Methods: In total, 483 patients with LS-SCCE were screened from five centers from June 2001 to June 2020, and 128 patients with LS-SCCE were screened from the Surveillance, Epidemiology, and End Results (SEER) database.

Lifetime management considerations to optimise transcatheter aortic valve implantation: a practical guide.

Transcatheter aortic valve implantation (TAVI) is a safe and effective procedure for the treatment of aortic stenosis. With the recently broadened indications, there is a larger cohort of patients likely to outlive their first transcatheter heart valve (THV). This review discusses relevant lifetime planning considerations, focusing on the utility of preprocedural computed tomography imaging to help implanters future-proof their patients who are likely to outlive their first valve.

Advances and Challenges in Prenatal Detection and Genetic Diagnosis of Upper Limb Anomalies: Analysis of a South London and Kent Cohort.

Objective: Prenatal detection and genetic diagnosis of congenital upper limb anomalies is particularly challenging due to both anatomical and technological factors. Hereby, we present a cross-sectional description of clinical and genetic findings in a 188-patient cohort.

Method: In this retrospective study, we present 188 cases with prenatally or postnatally detected upper limb anomalies, either isolated, associated with other anomalies, or syndromic.

Unraveling the cGAS/STING signaling mechanism: impact on glycerolipid metabolism and diseases.

The cyclic GMP-AMP synthase (cGAS) and its downstream effector, the stimulator of interferon genes (STING), are crucial components of the innate immune response, traditionally recognized for their role in detecting cytosolic DNA from pathogens and damaged host cells. However, recent research indicates that the cGAS-STING pathway also significantly impacts metabolic processes, particularly glycerolipid metabolism. Glycerolipids are essential for energy storage and cellular membrane integrity, and their dysregulation is linked to metabolic disorders such as obesity, insulin resistance, and non-alcoholic fatty liver disease (NAFLD).

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation.

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017.

Chronic kidney disease-associated pruritus: a comparison of instruments and associations with patient-reported outcomes using an electronic patient-reported outcome survey in Europe.

Background: The associations between self-reported chronic kidney disease-associated pruritus (CKD-aP) and patient-reported outcomes (PROs) have been reported using various instruments to assess itch. Data collection via multiple CKD-aP instruments allows the evaluation of different domains and measurements of CKD-aP burden and may help tailor data capture for future research or clinical care.

Methods: An electronic PRO (ePRO) survey was distributed to European hemodialysis (HD) patients enrolled in the Dialysis Outcomes and Practice Patterns Study (DOPPS) in 2021-23.

Cervical cesarean damage as a growing clinical problem: The association between in-labour cesarean section and recurrent preterm birth in subsequent pregnancies.

Increasing evidence supports an association between in-labour cesarean section and recurrent preterm birth in subsequent pregnancies. This clinically challenging problem may be caused by cervical damage at the time of in-labour cesarean section.

Management of acute decompensated valvular heart disease.

Worldwide, valvular heart disease (VHD) is a common cause of hospitalization for acute heart failure. In acute heart failure caused by VHD, symptoms result from rapid haemodynamic changes and subsequent decline in cardiac function, and if left untreated, leads to acute decompensation and cardiogenic shock. Current evidence remains scarce and recommendations regarding the management of acute heart failure caused by VHD are lacking in most recent international guidelines.

Tricuspid Valve S-Curves and Chamber Views: Implications for Transcatheter Tricuspid and Pulmonary Valve Interventions, Part 2 of the S-Curves and Chamber Views Series.

Despite the challenges associated with periprocedural imaging, transcatheter tricuspid valve interventions have shown important impact on outcomes. A comprehensive understanding of the anatomy of the right heart and surrounding structures is crucial. One way to optimize these interventions is by identifying the optimal fluoroscopic viewing angles along the S-curve of the tricuspid valve.

Site-specific π-clamp-mediated radiosynthesis of Ga and F PET radiopharmaceuticals.

The π-clamp-mediated conjugation method, which enables site-specific modification of cysteine residues, is a promising strategy for developing well-defined radiolabelled biomolecules for positron emission tomography (PET) imaging. We have applied this method to site-specifically attach the macrocyclic chelators "NODA" and "NODAGA" to the somatostatin receptor 2-targeted peptide, octreotate. The resulting novel NODA-octreotate and NODAGA-octreotate compounds can be radiolabelled with either [F]AlF or [Ga]Ga respectively.

Prolonged weaning from mechanical ventilation: who, what, when and how?

Weaning from invasive mechanical ventilation is an important part of the management of respiratory failure patients. Patients can be classified into those who wean on the first attempt (simple weaning), those who require up to three attempts (difficult weaning) and those who require more than three attempts (prolonged weaning). The process of weaning includes adequately treating the underlying cause of respiratory failure, assessing the readiness to wean, evaluating the response to a reduction in ventilatory support, and eventually liberation from mechanical ventilation and extubation or decannulation.

Impact of CT-angiography derived plaque characteristics on cardiac events in patients with a negative invasive fractional flow reserve.

Background: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for chronic coronary syndromes (CCS) improves outcomes compared with angiography-guided PCI, however cardiac events still occur during long-term follow-up of FFR-negative patients. In the PREVENT study preventive PCI reduced cardiac-events in lesions which were FFR-negative (FFR > 0.80) and had intracoronary imaging defined vulnerable plaque.

Treatments for RYR1-related disorders.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: Primary objective To analyse the benefits and harms of pharmacological or other interventions (e.g.