Citations

AbstractObjectivesTo compare long‐term transplant outcomes (organ rejection and retransplant) of simultaneous liver/kidney transplant (SLK) versus isolated kidney transplant (IK) for patients with primary hyperoxaluria (PH).MethodsThe Rare Kidney Stone Consortium PH registry was queried to identify patients with PH who underwent SLK or IK from 1999 to 2021. Patient characteristics and long‐term transplant outcomes were abstracted and analyzed. Statistical comparisons were performed with Kaplan–Meier plots and Cox proportional hazards models.ResultsWe identified 250 patients with PH, of whom 35 received care at Mayo Clinic and underwent SLK or IK. Patients who underwent SLK as their index transplant had lower odds of kidney rejection than did those who underwent IK (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.08–0.99; p = .048). The immunoprotective effect of concomitant liver and kidney transplant appeared to enhance outcomes for patients with PH. Additionally, the odds of retransplant were significantly lower for patients who underwent SLK as their index transplant than for those who underwent IK (HR, 0.08; 95% CI, 0.02–0.42; p = .003). Of five patients who underwent IK and had maintained graft function for at least 5 years after transplant, three (60%) had documented vitamin B6 responsiveness.ConclusionsPatients with PH who underwent SLK had a lower risk of kidney rejection and retransplant than those who underwent IK. Accurate genetic assessment for vitamin B6 responsiveness may optimize IK allocation. Novel therapeutics, such as lumasiran, have been introduced as promising agents for the management of PH.

Abstract Clonal cytopenia of undetermined significance (CCUS) represents a distinct disease entity characterized by myeloid-related somatic mutations with a variant allele fraction of ≥2% in individuals with unexplained cytopenia(s) but without a myeloid neoplasm (MN). Notably, CCUS carries a risk of progressing to MN, particularly in cases featuring high-risk mutations. Understanding CCUS requires dedicated studies to elucidate its risk factors and natural history. Our analysis of 357 patients with CCUS investigated the interplay between clonality, cytopenia, and prognosis. Multivariate analysis identified 3 key adverse prognostic factors: the presence of splicing mutation(s) (score = 2 points), platelet count of <100 × 109/L (score = 2.5), and ≥2 mutations (score = 3). Variable scores were based on the coefficients from the Cox proportional hazards model. This led to the development of the clonal cytopenia risk score (CCRS), which stratified patients into low- (score of <2.5 points), intermediate- (score of 2.5 to <5), and high-risk (score of ≥5) groups. The CCRS effectively predicted 2-year cumulative incidence of MN for low- (6.4%), intermediate- (14.1%), and high-risk (37.2%) groups, respectively, by the Gray test (P < .0001). We further validated the CCRS by applying it to an independent CCUS cohort of 104 patients, demonstrating a c-index of 0.64 (P = .005) in stratifying the cumulative incidence of MN. Our study underscores the importance of integrating clinical and molecular data to assess the risk of CCUS progression, making the CCRS a valuable tool that is practical and easily calculable. These findings are clinically relevant, shaping the management strategies for CCUS and informing future clinical trial designs.

AbstractPulmonary fibrosis is characterized by pathological accumulation of scar tissue in the lung parenchyma. Many of the processes that are implicated in fibrosis, including increased extracellular matrix synthesis, also occur following pneumonectomy (PNX), but PNX instead results in regenerative compensatory growth of the lung. As fibroblasts are the major cell type responsible for extracellular matrix production, we hypothesized that comparing fibroblast responses to PNX and bleomycin (BLM) would unveil key differences in the role they play during regenerative versus fibrotic lung responses. RNA‐sequencing was performed on flow‐sorted fibroblasts freshly isolated from mouse lungs 14 days after BLM, PNX, or sham controls. RNA‐sequencing analysis revealed highly similar biological processes to be involved in fibroblast responses to both BLM and PNX, including TGF‐β1 and TNF‐α. Interestingly, we observed smaller changes in gene expression after PNX than BLM at Day 14, suggesting that the fibroblast response to PNX may be muted by expression of transcripts that moderate pro‐fibrotic pathways. Itpkc, encoding inositol triphosphate kinase C, was a gene uniquely up‐regulated by PNX and not BLM. ITPKC overexpression in lung fibroblasts antagonized the pro‐fibrotic effect of TGF‐β1. RNA‐sequencing analysis has identified considerable overlap in transcriptional changes between fibroblasts following PNX and those overexpressing ITPKC.

Abstract Surgical abdominal emergencies among patients with cerebral palsy (CP) are infrequently reported. The most commonly reported reason for urgent and emergent abdominal surgery among patients with CP is intestinal volvulus. Intestinal volvulus leads to obstruction and vascular compromise, potentially resulting in life-threatening ischemia and necrosis. Volvulus typically presents with abdominal pain and decreased bowel function. When patients are nonverbal and have baseline bowel dysfunction, symptoms of volvulus can be difficult to diagnose. Here, we present a case of an adult female patient with CP who presented with ischemic colitis with perforation and underwent emergency total colectomy and end-ileostomy. Her postoperative course was complicated by two episodes of intestinal volvulus that occurred one and three months after the initial operation. At the second presentation, she had global bowel ischemia due to the volvulus, which led to her death. We have reviewed and summarized the current literature regarding abdominal emergencies among patients with CP.

BACKGROUND: Fenestrated-branched endovascular aortic repair (FB-EVAR) has been used as a minimally invasive alternative to open surgical repair to treat patients with thoracoabdominal aortic aneurysms (TAAAs). The aim of this study was to evaluate aortic-related mortality (ARM) and aortic aneurysm rupture after FB-EVAR of TAAAs. METHODS: Patients enrolled in 8 prospective, nonrandomized, physician-sponsored investigational device exemption studies between 2005 and 2020 who underwent elective FB-EVAR of asymptomatic intact TAAAs were analyzed. Primary end points were ARM, defined as any early mortality (30 days or in hospital) or late mortality from aortic rupture, dissection, organ or limb malperfusion attributable to aortic disease, complications of reinterventions, or aortic rupture. Secondary end points were early major adverse events, TAAA life-altering events (defined as death, permanent spinal cord injury, permanent dialysis, or stroke), all-cause mortality, and secondary interventions. RESULTS: A total of 1109 patients were analyzed; 589 (53.1%) had extent I–III and 520 (46.9%) had extent IV TAAAs. Median age was 73.4 years (interquartile range, 68.1–78.3 years); 368 (33.2%) were women. Early mortality was 2.7% (n=30); congestive heart failure was associated with early mortality (odds ratio, 3.30 [95% CI, 1.22–8.02]; P =0.01). Incidence of early aortic rupture was 0.4% (n=4). Incidence of early major adverse events and TAAA life-altering events was 20.4% (n=226) and 7.7% (n=85), respectively. There were 30 late ARMs; 5-year cumulative incidence was 3.8% (95% CI, 2.6%–5.4%); older age and extent I–III TAAAs were independently associated with late ARM (each P <0.05). Fourteen late aortic ruptures occurred; 5-year cumulative incidence was 2.7% (95% CI, 1.2%–4.3%); extent I–III TAAAs were associated with late aortic rupture (hazard ratio, 5.85 [95% CI, 1.31–26.2]; P =0.02). Five-year all-cause mortality was 45.7% (95% CI, 41.7%–49.4%). Five-year cumulative incidence of secondary intervention was 40.3% (95% CI, 35.8%–44.5%). CONCLUSIONS: ARM and aortic rupture are uncommon after elective FB-EVAR of asymptomatic intact TAAAs. Half of the ARMs occurred early, and most of the late deaths were not aortic related. Late all-cause mortality rate and the need for secondary interventions were 46% and 40%, respectively, 5 years after FB-EVAR. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT02089607, NCT02050113, NCT02266719, NCT02323581, NCT00583817, NCT01654133, NCT00483249, NCT02043691, and NCT01874197.

BACKGROUND: Physician modified endografts (PMEGs) have been widely used in the treatment of complex abdominal aortic aneurysm and thoracoabdominal aortic aneurysm, however, previous data are limited to small single center studies and robust data on safety and effectiveness of PMEGs are lacking. We aimed to perform an international multicenter study analyzing the outcomes of PMEGs in complex abdominal aortic aneurysms and thoracoabdominal aortic aneurysms. METHODS: An international multicenter single-arm cohort study was performed analyzing the outcomes of PMEGs in the treatment of elective, symptomatic, and ruptured complex abdominal aortic aneurysms and thoracoabdominal aortic aneurysms. Variables and outcomes were defined according to the Society for Vascular Surgery reporting standards. Device modification and procedure details were collected and analyzed. Efficacy outcomes included technical success and safety outcomes included major adverse events and 30-day mortality. Follow-up outcomes included reinterventions, endoleaks, target vessel patency rates and overall and aortic-related mortality. Multivariable analysis was performed aiming at identifying predictors of technical success, 30-day mortality, and major adverse events. RESULTS: Overall, 1274 patients were included in the study from 19 centers. Median age was 74 (IQR, 68–79), and 75.7% were men; 45.7% were complex abdominal aortic aneurysms, and 54.3% were thoracoabdominal aortic aneurysms; 65.5% patients presented electively, 24.6% were symptomatic, and 9.9% were ruptured. Most patients (83.1%) were submitted to a fenestrated repair, 3.6% to branched repair, and 13.4% to a combined fenestrated and branched repair. Most patients (85.8%) had ≥3 target vessels included. The overall technical success was 94% (94% in elective, 93.4% in symptomatic, and 95.1% in ruptured cases). Thirty-day mortality was 5.8% (4.1% in elective, 7.6% in symptomatic, and 12.7% in ruptured aneurysms). Major adverse events occurred in 25.2% of cases (23.1% in elective, 27.8% in symptomatic, and 30.3% in ruptured aneurysms). Median follow-up was 21 months (5.6–50.6). Freedom from reintervention was 73.8%, 61.8%, and 51.4% at 1, 3, and 5 years; primary target vessel patency was 96.9%, 93.6%, and 90.3%. Overall survival and freedom from aortic-related mortality was 82.4%/92.9%, 69.9%/91.6%, and 55.0%/89.1% at 1, 3, and 5 years. CONCLUSIONS: PMEGs were a safe and effective treatment option for elective, symptomatic, and ruptured complex aortic aneurysms. Long-term data and future prospective studies are needed for more robust and detailed analysis.

IntroductionCervical spine defects result in spinal instability, putting the spinal cord and vertebral arteries at risk of damage and possibly devastating neurological injuries. The fibula free flap can span the spinal defects for stability. There is a paucity of literature on this technique.MethodMulti‐institutional retrospective case series reviewing patients who underwent cervical spine reconstruction with a fibula free flap. Patient demographic information, comorbidities, characteristics of cervical spine defects, and free flap complications were collected.ResultsA total of 1187 fibula free flaps across 10 different institutions were reviewed. Thirteen patients (1.09%) underwent cervical spine reconstruction with a fibula free flap. Average age was 52.3 years old with an age range of 12–79 years. There were six males (46.1%) and seven females (53.8%). The most common defect etiology was infection (n = 6, 46.1%). Most commonly involved cervical spine level of the defect was C5 (n = 10) followed by C6 (n = 9) and C4 (n = 8). The majority of reconstructed defects spanned three or more cervical levels, (n = 9, 69.2%). Facial artery was the most common arterial anastomosis (n = 8). Eight patients (61.5%) required a tracheostomy during their postoperative course. None of the patients had symptomatic or radiographic nonunion.ConclusionThis case series demonstrates that a vascularized fibula flap is a potential reconstructive option for cervical spine defects, especially in defects greater than three cervical levels, in the setting of infection, and previously radiated patients.Level of Evidence4 Laryngoscope, 134:4923–4928, 2024

Purpose To assess the efficacy and safety of dexmedetomidine as an adjuvant to intra‐articular (IA) injections of local anesthetics (LA) in adult patients undergoing knee arthroscopy. Methods We searched MEDLINE, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing IA dexmedetomidine plus LA versus LA alone for knee arthroscopy in adults. We used the DerSimonian and Laird random‐effects model for all outcomes and conducted a sensitivity analysis with the leave‐one‐out method, as well as a subgroup analysis for the type of LA. We used R version 4.1.2 for all statistical analyses. Results We included 16 RCTs encompassing 799 patients, of whom 49.8% received IA dexmedetomidine. In the pooled analysis, time to first analgesia rescue was prolonged in almost 4 hours with the use of dexmedetomidine (mean difference [MD] 229 minutes; P < .001). We found statistically significant differences favoring dexmedetomidine in pain scores at rest and movement throughout the first 2, 6, 12, and 24 hours postoperatively ( P < .001). Although the MD ranged from –0.3 to –0.9 cm, corresponding to a 3% to 9% reduction in pain scores, this change is not clinically significant compared with the minimal clinically important difference (MCID). Additionally, the intervention group showed a statistically significant reduction in cumulative opioid consumption over 24 hours (MD –4.5 mg; P < .001). However, this reduction did not meet the threshold for the MCID. There was no difference between groups on the incidence of hypotension ( P = .190), bradycardia ( P = .430), and postoperative nausea and vomiting ( P = .550). Conclusions Adding dexmedetomidine to LA in IA injections for knee arthroscopy significantly extended analgesia duration. Additionally, it lowered pain scores and opioid use, although these effects did not reach the MCID. Furthermore, this addition did not increase the risk of adverse events. Level of Evidence Level II, meta‐analysis of Level I and II studies.

Abstract Context Mild autonomous cortisol secretion (MACS) is diagnosed based on postdexamethasone cortisol &gt;1.8 µg/dL. Scarce evidence exists on steroid circadian secretion and steroid metabolome in MACS. Objective To characterize 24-hour (h) urine steroid metabolome in patients with MACS and determine circadian differences in urine steroid profiling and cortisol concentrations in patients with MACS vs referent subjects. Methods Cross-sectional study, 2018-2023, at a referral center. Patients with MACS and age-, sex-, body mass index–, and menopausal status–matched referent subjects were included. Urine was collected over a 24 hour period as separate daytime and nighttime collections. High-resolution mass spectrometry assay was used to measure 25 steroids. A subgroup of patients and referent subjects was admitted for serum measurements of free and total cortisol every 2 hours. Outcomes were steroids, steroid sums, and ratios. Results Patients with MACS (n = 72) had lower µg/24 hour median androgens (2084 vs 3283, P &lt; .001), higher glucocorticoids (15 754 vs 12936, P &lt; .001), and higher glucocorticoid/androgen ratio (8.7 vs 3.9, P &lt; .001) than referent subjects. Patients also had lower steroid day/night ratios than referent subjects, reflecting a higher relative nocturnal steroid production in MACS. In a subgroup of 12 patients with MACS and 10 referent subjects, the 24-hour areas under the curve for total and free serum cortisol were similar. However, evening mean total (5.3 vs 4.0 µg/dL, P = .056) and free (0.2 vs 0.1 µg/dL, P = .035) cortisol was higher in patients vs referent subjects. Conclusion Patients with MACS demonstrate an abnormal urine steroid metabolome, with a high glucocorticoid to androgen ratio, and a higher nocturnal steroid production.