Citations

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is associated with significant morbidity and mortality. While liver transplantation is the definitive treatment, continuous terlipressin infusion for HRS-AKI may provide benefit and, as such, was assessed in a population composed of candidates for liver transplant (LT). Fifty hospitalized LT-eligible patients with HRS-AKI received a single bolus followed by continuous terlipressin infusion. Acute-on-chronic liver failure grade 3, serum creatinine (SCr)>5.0 mg/dL, or Model for End-Stage Liver Disease (MELD) ≥35 were exclusions. Fifty hospitalized patients who received midodrine and octreotide or norepinephrine for HRS-AKI served as a historical comparator cohort. Complete response (CR) was defined as a ≥30% decrease in SCr with end-of-treatment (EOT) SCr≤1.5, partial response as a ≥30% decrease in SCr with EOT SCr>1.5, and nonresponse as a <30% decrease in SCr. CR rate was significantly higher in the terlipressin cohort compared to the historical cohort (64% vs. 16%, p<0.001). Survival, while numerically higher in those who received terlipressin, was statistically similar (D30: 94% vs. 82%, p=0.12; D90: 78% vs. 68%, p=0.37). Renal replacement therapy (RRT) was more common among terlipressin NR than CR and PR (70% vs. 3% vs. 13%, p < 0.001). EOT MELD and SCr were significantly lower within terlipressin cohort (MELD: 19 vs. 25, SCr: 1.4 vs. 2.1 mg/dL, p<0.001). Sixteen of 40 terlipressin-treated patients received LT-alone (terlipressin CR in 10/16). One patient on terlipressin had a hypoxic respiratory failure that responded to diuretics; one possibly had drug-related rash. With continuous terlipressin infusion, a CR rate of 64% was observed with a favorable safety profile. Terlipressin use was associated with lower EOT MELD and SCr than the historical midodrine and octreotide/norepinephrine cohort; LT-alone was accomplished in a high proportion of complete terlipressin responders.

Alloreactive memory, unlike naive, CD8 + T cells resist transplantation tolerance protocols and are a critical barrier to long-term graft acceptance in the clinic. We here show that semiallogeneic pregnancy successfully reprogrammed memory fetus/graft-specific CD8 + T cells (T FGS ) toward hypofunction. Female C57BL/6 mice harboring memory CD8 + T cells generated by the rejection of BALB/c skin grafts and then mated with BALB/c males achieved rates of pregnancy comparable with naive controls. Postpartum CD8 + T FGS from skin-sensitized dams upregulated expression of T cell exhaustion (T EX ) markers (Tox, Eomes, PD-1, TIGIT, and Lag3). Transcriptional analysis corroborated an enrichment of canonical T EX genes in postpartum memory T FGS and revealed a downregulation of a subset of memory-associated transcripts. Strikingly, pregnancy induced extensive epigenetic modifications of exhaustion- and memory-associated genes in memory T FGS , whereas minimal epigenetic modifications were observed in naive T FGS . Finally, postpartum memory T FGS durably expressed the exhaustion-enriched phenotype, and their susceptibility to transplantation tolerance was significantly restored compared with memory T FGS . These findings advance the concept of pregnancy as an epigenetic modulator inducing hypofunction in memory CD8 + T cells that has relevance not only for pregnancy and transplantation tolerance, but also for tumor immunity and chronic infections.

AbstractTissue ablation techniques have emerged as a critical component of modern medical practice and biomedical research, offering versatile solutions for treating various diseases and disorders. Percutaneous ablation is minimally invasive and offers numerous advantages over traditional surgery, such as shorter recovery times, reduced hospital stays, and decreased healthcare costs. Intra‐procedural imaging during ablation also allows precise visualization of the treated tissue while minimizing injury to the surrounding normal tissues, reducing the risk of complications. Here, the mechanisms of tissue ablation and innovative energy delivery systems are explored, highlighting recent advancements that have reshaped the landscape of clinical practice. Current clinical challenges related to tissue ablation are also discussed, underlining unmet clinical needs for more advanced material‐based approaches to improve the delivery of energy and pharmacology‐based therapeutics.

Background: Despite the prevalence and incidence of kidney stones progressively increasing worldwide, public awareness of this condition remains unclear. Understanding trends of awareness can assist healthcare professionals and policymakers in planning and implementing targeted health interventions. This study investigated online search interest in “kidney stone” by analyzing Google Trends, focusing on stationarity of the trends and predicting future trends. Methods: We performed time series analysis on worldwide Google monthly search data from January 2004 to November 2023. The Augmented Dickey–Fuller (ADF) test was used to assess the stationarity of the data, with a p-value below 0.05 indicating stationarity. Time series forecasting was performed using the autoregressive integrated moving average to predict future trends. Results: The highest search interest for “kidney stone” (score 100) was in August 2022, while the lowest was in December 2007 (score 36). As of November 2023, search interest remained high, at 92. The ADF test was significant (p = 0.023), confirming data stationarity. The time series forecasting projected continued high public interest, likely reflecting ongoing concern and awareness. Notably, diverse regions such as Iran, the Philippines, Ecuador, the United States, and Nepal showed significant interest, suggesting widespread awareness of nephrolithiasis. Conclusion: This study highlighted that “kidney stone” is a consistently relevant health issue globally. The increase and stationarity of search trends, the forecasted sustained interest, and diverse regional interest emphasize the need for collaborative research and educational initiatives. This study’s analysis serves as a valuable tool for shaping future healthcare policies and research directions in addressing nephrolithiasis related health challenges.

Proton therapy has emerged as a crucial tool in the treatment of head and neck and skull-base cancers, offering advantages over photon therapy in terms of decreasing integral dose and reducing acute and late toxicities, such as dysgeusia, feeding tube dependence, xerostomia, secondary malignancies, and neurocognitive dysfunction. Despite its benefits in dose distribution and biological effectiveness, the application of proton therapy is challenged by uncertainties in its relative biological effectiveness (RBE). Overcoming the challenges related to RBE is key to fully realizing proton therapy’s potential, which extends beyond its physical dosimetric properties when compared with photon-based therapies. In this paper, we discuss the clinical significance of RBE within treatment volumes and adjacent serial organs at risk in the management of head and neck and skull-base tumors. We review proton RBE uncertainties and its modeling and explore clinical outcomes. Additionally, we highlight technological advancements and innovations in plan optimization and treatment delivery, including linear energy transfer/RBE optimizations and the development of spot-scanning proton arc therapy. These advancements show promise in harnessing the full capabilities of proton therapy from an academic standpoint, further technological innovations and clinical outcome studies, however, are needed for their integration into routine clinical practice.

Abstract Purpose The demographic and radiological risk factors of subchondral insufficiency fractures of the knee (SIFK) continue to be a subject of debate. The purpose of this study was to associate patient‐specific factors with SIFK in a large cohort of patients. Methods Inclusion criteria consisted of patients with SIFK as verified on magnetic resonance imaging (MRI). All radiographs and MRIs were reviewed to assess characteristics such as meniscus tear presence and type, subchondral oedema presence and location, location of SIFK, mechanical limb alignment, osteoarthritis as assessed by Kellgren–Lawrence grade and ligamentous injury. A total of 253 patients (253 knees) were included, with 171 being female. The average body mass index (BMI) was 32.1 ± 7.0 kg/m 2 . Results SIFK was more common in patients with medial meniscus tears (77.1%, 195/253) rather than tears of the lateral meniscus (14.6%, 37/253) ( p < 0.001). Medial meniscus root and radial tears of the posterior horn were present in 71.1% (180/253) of patients. Ninety‐one percent (164/180) of medial meniscus posterior root and radial tears had an extrusion ≥3.0 mm. Eighty‐one percent (119/147) of patients with SIFK on the medial femoral condyle and 86.8% (105/121) of patients with SIFK on the medial tibial plateau had a medial meniscus tear. Varus knees had a significantly increased rate of SIFK on the medial femoral condyle in comparison to valgus knees ( p = 0.016). Conclusion In this large cohort of patients with SIFK, there was a high association with medial meniscus root and radial tears of the posterior horn, meniscus extrusion ≥3.0 mm as well as higher age, female gender and higher BMI. Additionally, there was a particularly strong association of medial compartment SIFK with medial meniscus tears. As SIFK is frequently undiagnosed, identifying patient‐specific demographic and radiological risk factors will help achieve a prompt diagnosis. Level of Evidence Level IV.

Abstract Background Older adults presenting with trauma have worse outcomes than younger adults. Starting in 2016, we provided geriatrics consultation (GC) to older adults admitted to the trauma service. We aimed to analyze the impact of GC on patient outcomes. Methods We performed a retrospective pre–post study and year‐matched cohort study. We identified patients from the trauma registry at our level 1 trauma center. In the pre–post study, we compared patients who received GC (2016–2022) with controls (2011–2015). In the cohort study (2016–2022), we compared patients who received GC with controls. We matched for age, race, sex, and injury severity score (ISS) in both studies, as well as admission year in the cohort study. Outcome variables included mortality (in‐hospital, 30‐day, 90‐day), length of stay (LOS), discharge disposition, and hospital readmission rates (30‐day, 90‐day). Results We analyzed 1968 patients in the pre–post study and 2544 patients in the cohort study. Patients were similar in age, race, and sex. GC patients had a slightly higher ISS score and a higher rate of ICU stay. Delirium occurrence was lower among GC patients. GC patients had lower in‐hospital mortality compared to controls (pre–post OR 0.27, p < 0.001; cohort OR 0.31, p < 0.001) and increased LOS (6 days vs 4 days, p < 0.001; both studies). GC patients in the cohort study also had lower 30‐ and 90‐day mortality (OR 0.52 and 0.65, p < 0.01) and were less likely to return home (OR 0.81, p < 0.01); similar trends, though not statistically significant, were noted in the pre–post study. Lower readmission rates (statistically non‐significant) were noted in the GC group across both studies. Conclusions GC in older adults with trauma has proven benefit with reduced mortality and a trend toward lower readmission rates but was associated with increased LOS and higher rates of discharge to skilled facility.