Citations

Repair and regeneration of a diseased lung using stem cells or bioengineered tissues is an exciting therapeutic approach for a variety of lung diseases and critical illnesses. Over the past decade, increasing evidence from preclinical models suggests that mesenchymal stromal cells, which are not normally resident in the lung, can be used to modulate immune responses after injury, but there have been challenges in translating these promising findings to the clinic. In parallel, there has been a surge in bioengineering studies investigating the use of artificial and acellular lung matrices as scaffolds for three-dimensional lung or airway regeneration, with some recent attempts of transplantation in large animal models. The combination of these studies with those involving stem cells, induced pluripotent stem cell derivatives, and/or cell therapies is a promising and rapidly developing research area. These studies have been further paralleled by significant increases in our understanding of the molecular and cellular events by which endogenous lung stem and/or progenitor cells arise during lung development and participate in normal and pathological remodeling after lung injury. For the 2023 Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases Conference, scientific symposia were chosen to reflect the most cutting-edge advances in these fields. Sessions focused on the integration of “omics” technologies with function, the influence of immune cells on regeneration, and the role of the extracellular matrix in regeneration. The necessity for basic science studies to enhance fundamental understanding of lung regeneration and to design innovative translational studies was reinforced throughout the conference.

Abstract Background Perioperative morbidity and mortality remain a point of concern for the Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy (ALPPS) procedure. Post-hepatectomy liver failure (PHLF) after the second step poses the most significant risk factor for futile outcome. Recovery of liver function after the first step of ALPPS is critically important to allow for sufficient liver function after this surgery. The APRI+ALBI score has been proposed as an easily assessable score to monitor liver function and its dynamic recovery. Aims We explored if the APRI+ALBI score was able to assess liver function recovery after the first step of ALPPS and allow for optimal timing of the 2nd step. Methods Based on the ALPPS registry, patients from 2012 to 2020 with available APRI+ALBI score were included. Postoperative outcomes (PHLF A – C, PHLF B + C, 90-day mortality and severe morbidity) were defined as per standard definitions. The APRI/ALBI score was monitored perioperatively. Results Overall, 464 patients from 16 international participating centers in the ALPPS registry were included. Clinically relevant PHLF (B + C) was observed in 7.5 % and of these 63 % of patients ultimately died due to liver failure. The APRI+ALBI score immediately increased after each surgical intervention and continuously decrease thereafter. Failure of the APRI+ALBI score to decrease until the 2nd step of ALPPS predicted PHLF B+C (p = 0.001; AUC 0.78). Particularly patients with high APRI+ALBI scores and short interstage intervals were at risk to develop PHLF B+C. Conclusion The APRI+ALBI score objectifies liver function recovery after the 1st step of ALPPS and failure to sufficiently decreased is associated with a higher risk for PHLF B+C. This might allow for optimized planning of the 2nd step of ALPPS to allow for sufficient liver function recovery to minimize the risk for PHLF B+C and associated futile outcome.

OBJECTIVE The role of interbodies in lumbar arthrodesis has been insufficiently supported by evidence, impacting clinical decision-making and occasionally insurance coverage. This study aimed to compare clinical and radiological outcomes between lumbar arthrodesis with a synthetic interbody spacer (cage) versus structural bone graft alone (autograft or allograft) in patients with degenerative spine disease. METHODS A systematic review of the literature was performed to identify studies directly comparing outcomes of lumbar interbody arthrodesis with and without interbody cage use. The outcomes of individual studies were synthesized in meta-analyses using random-effects models. RESULTS Twenty studies with 1508 patients (769 with an interbody cage and 739 without an interbody cage) were included. Interbody cage placement was associated with a significantly greater increase in disc height after surgery (4.0 mm vs 3.4 mm, p < 0.01). There was a significantly greater reduction of back pain (visual analog scale [VAS] score) in cases in which an interbody cage was used (5.4 vs 4.7, p = 0.03). Fusion rates were 5.5% higher in the cage group (96.3% vs 90.8%) and reached statistical significance (p = 0.03). No statistically significant differences were identified between the two groups regarding all-cause reoperation rates, complication rates, or improvement in Oswestry Disability Index score or leg pain (VAS score). CONCLUSIONS These results suggest that implantation of an interbody cage is associated with higher rates of fusion, more effective maintenance of disc height, and greater improvement of back pain. This study underlines the clinical value of interbody cages in lumbar arthrodesis for patients with degenerative spine disease.

Abstract Atrial fibrillation (AF) is a globally prevalent cardiac arrhythmia with significant genetic underpinnings, as highlighted by recent large-scale genetic studies. A prominent clinical and genetic overlap exists between AF, heritable ventricular cardiomyopathies, and arrhythmia syndromes, underlining the potential of AF as an early indicator of severe ventricular disease in younger individuals. Indeed, several recent studies have demonstrated meaningful yields of rare pathogenic variants among early-onset AF patients (∼4%–11%), most notably for cardiomyopathy genes in which rare variants are considered clinically actionable. Genetic testing thus presents a promising opportunity to identify monogenetic defects linked to AF and inherited cardiac conditions, such as cardiomyopathy, and may contribute to prognosis and management in early-onset AF patients. A first step towards recognizing this monogenic contribution was taken with the Class IIb recommendation for genetic testing in AF patients aged 45 years or younger by the 2023 American College of Cardiology/American Heart Association guidelines for AF. By identifying pathogenic genetic variants known to underlie inherited cardiomyopathies and arrhythmia syndromes, a personalized care pathway can be developed, encompassing more tailored screening, cascade testing, and potentially genotype-informed prognosis and preventive measures. However, this can only be ensured by frameworks that are developed and supported by all stakeholders. Ambiguity in test results such as variants of uncertain significance remain a major challenge and as many as ∼60% of people with early-onset AF might carry such variants. Patient education (including pretest counselling), training of genetic teams, selection of high-confidence genes, and careful reporting are strategies to mitigate this. Further challenges to implementation include financial barriers, insurability issues, workforce limitations, and the need for standardized definitions in a fast-moving field. Moreover, the prevailing genetic evidence largely rests on European descent populations, underscoring the need for diverse research cohorts and international collaboration. Embracing these challenges and the potential of genetic testing may improve AF care. However, further research—mechanistic, translational, and clinical—is urgently needed.

The treatment for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) with immune checkpoint inhibitors (anti-PD1) with or without chemotherapy has led to an improvement in survival. Yet, despite this therapeutic advancement, only 15%-19% of patients remain alive at four years, highlighting the poor survival and unmet need for improved therapies for this patient population. Some of the key evolving novel therapeutics beyond anti-PD1 in R/M HNSCC have included therapeutic vaccine therapies, bispecific antibodies/fusion proteins and multitargeted kinase inhibitors, and antibody-drug conjugates (ADCs). Multiple concurrent investigations of novel therapeutics for patients with R/M HNSCC beyond anti-PD(L)1 inhibition are currently underway with some promising early results. Beyond immune checkpoint inhibition, novel immunotherapeutic strategies including therapeutic vaccines ranging from targeting human papillomavirus–specific epitopes to personalized neoantigen vaccines are ongoing with some early efficacy signals and large, randomized trials. Other novel weapons including bispecific antibodies, fusion proteins, and multitargeted kinase inhibitors leverage multiple concurrent targets and modulation of the tumor microenvironment to harness antitumor immunity and inhibition of protumorigenic signaling pathways with emerging promising results. Finally, as with other solid tumors, ADCs remain a promising therapeutic intervention either alone or in combination with immunotherapy for patients with R/M HNSCC. With early enthusiasm across novel therapies in R/M HNSCC, results of larger randomized trials in R/M HNSCC are eagerly awaited.

AbstractProfessional standards for academic health care system pharmacy departments and clinical pharmacists advocate for research and scholarly activities. Developing and sustaining a research program in a clinical pharmacy department is challenging. Over the span of a decade, a robust pharmacy research program was developed in an academic medical center not affiliated with a college of pharmacy. The aim of this manuscript is to provide a framework suitable for scaling research in pharmacy departments within an academic medical center. Objectives to accomplish the aim includes describing the structure and evolution of the clinical pharmacy department research program, listing measurable outputs and achievements of the pharmacists and the program and describing the barriers encountered and solutions that were enacted to overcome them. Elements critical to building and sustaining a research program in the pharmacy department included long‐term commitment from within the department, a departmental research infrastructure, support from institutional leadership, research funding from the institution, and a growth mindset in accordance with company initiatives to support evolving research needs. A research curriculum was developed for pharmacy residents and pharmacists, created electronic tools for research proposal scientific reviews and allocation of funds, and established departmental research career development awards that allowed for protected time to pursue research and professional development. Over the first 10 years of the program, publication rates grew more than three‐fold, faculty appointments and promotions increased approximately five‐fold, and pharmacist investigators obtained extramural federal funding. Further offsetting clinical workload relative to dedicated research time remains a challenge. The experience and success at this academic medical center suggest it is feasible to develop a robust, sustainable clinical pharmacy department research program.