Outcomes of Patients Undergoing Combined Heart-Kidney Transplantation With or Without Prior Ventricular Assist Device.

BACKGROUND: Both combined heart-kidney transplantation and ventricular assist devices (VADs) pose significant challenges, including sensitization, immunosuppressive treatment, and infrastructure demands. Despite these challenges, we hypothesized that the recipients of combined heart-kidney transplants with and without VADs would have equivalent survival. We aimed to compare the survival of heart-kidney transplant recipients with and without prior VAD placement. METHODS: We retrospectively analyzed all patients enrolled in the United Network for Organ Sharing database who underwent heart-kidney transplants. We created a matched cohort of patients undergoing heart-kidney transplantation with or without prior VAD using 1:1 nearest propensity-score matching with preoperative variables. RESULTS: In the propensity-matched cohort, 399 patients underwent heart-kidney transplantation with prior VAD, and 399 underwent heart-kidney transplantation without prior VAD. The estimated survival of heart--kidney recipients with prior VAD was 84.8% at one year, 81.2% at 3 years, and 75.3% at 5 years. The estimated survival of heart-kidney recipients without prior VAD was 86.8.7% at one year, 84.0% at 3 years, and 78.8% at 5 years. There was no statistically significant difference in the survival of heart-kidney transplant recipients with or without prior VAD at one year (P = .42; Figure 2), 3 years (P = .34), or 5 years (P = .30). CONCLUSION: Despite the increased challenge of heart-kidney transplantation in recipients with prior VAD, we demonstrated that these patients have similar survival to those who underwent heart-kidney transplantation without previous VAD placement.

Acute kidney injury in patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. METHODS: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. RESULTS: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. CONCLUSIONS: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

Systematic Review and Meta-Analysis of Hardware Failure in Surgical Stabilization of Rib Fractures: Who, What, When, Where, and Why?

BACKGROUND: Surgical stabilization of rib fractures (SSRF) is increasingly used to reduce pulmonary complications and death among patients with rib fractures. However, the five Ws of hardware failure -who, what, when, where, and why- remains unclear. We aimed to synthesize available evidence on the five Ws and outline future research agenda for mitigating hardware failure. METHODS: Experimental and observational studies published between 2009 and 2020 evaluating adults undergoing SSRF for traumatic rib fractures underwent evidence synthesis. We performed random effects meta-analysis of cohort/consecutive case studies. We calculated pooled prevalence of SSRF hardware failures using Freeman-Tukey double arcsine transformation and assessed study heterogeneity using DerSimonian-Laird estimation. We performed meta-regression with rib fracture acuity (acute or chronic) and hardware type (metal plate or not metal plate) as moderators. RESULTS: Twenty-nine studies underwent qualitative synthesis and 24 studies (2404 SSRF patients) underwent quantitative synthesis. Pooled prevalence of hardware failure was 4(3-7)%. Meta-regression showed fracture acuity was a significant moderator (P = 0.002) of hardware failure but hardware type was not (P = 0.23). Approximately 60% of patients underwent hardware removal after hardware failure. Mechanical failures were the most common type of hardware failure, followed by hardware infections, pain/discomfort, and non-union. Timing of hardware failure after surgery was highly variable, but 87% of failures occurred after initial hospitalization. Mechanical failures was attributed to technical shortcomings (i.e. short plate length) or excessive force on the thoracic cavity. CONCLUSIONS: SSRF hardware failure is an uncommon complication. Not all hardware failures are consequential, but insufficient individual patient data precluded characterizing where and why hardware failures occur. Minimizing SSRF hardware failure requires concerted research agenda to expand on the paucity of existing evidence.

Heterogeneity in managing rib fractures across non-trauma and level I, II, and III trauma centers.

BACKGROUND: We aimed to elucidate management patterns and outcomes of high-risk patients with rib fractures (elderly or flail chest) across non-trauma and trauma centers. We hypothesized highest-capacity (level I) centers would have best outcomes for high-risk patients. METHODS: We queried the 2016 National Emergency Department Sample to identify adults presenting with rib fractures. Multivariable regression assessed ED and inpatient events across non-trauma and level III/II/I trauma centers. RESULTS: Among 504,085 rib fracture encounters, 46% presented to non-trauma centers. Elderly patients with multiple rib fractures had stepwise increase in inpatient admission odds and stepwise decrease in pneumonia odds at higher-capacity trauma centers compared to non-trauma centers. Among patients with flail chest, odds of undergoing surgical stabilization (SSRF) increased at trauma centers. Undergoing SSRF was associated with reduced mortality but remained underutilized. CONCLUSION: Half of patients with rib fractures present to non-trauma centers. Nationwide care-optimization for high-risk patients requires further effort.

Pulmonary contusions in patients with rib fractures: The need to better classify a common injury.

BACKGROUND: Pulmonary contusions are common injuries. Computed tomography reveals vast contused lung volume spectrum, yet pulmonary contusions are defined dichotomously (unilateral vs bilateral). We assessed whether there is stepwise increased risk of pulmonary complications among patients without, with unilateral, and with bilateral pulmonary contusion. METHODS: We identified adults admitted with rib fractures using the largest US inpatient database. After propensity-score-matching patients without vs with unilateral vs bilateral pulmonary contusions and adjusting for residual confounders, we compared risk for pneumonia, ventilator-associated pneumonia (VAP), respiratory failure, intubation, and mortality. RESULTS: Among 148,140 encounters of adults with multiple rib fractures, 19% had concomitant pulmonary contusions. Matched patients with pulmonary contusions had increased risk of pneumonia 19% [95%CI:16-33%], respiratory failure 40% [95%CI: 31-50%], and intubation 46% [95%CI: 33-61%]. Delineation showed bilateral contusions, not unilateral contusions, attributed to increased risk of complications. CONCLUSIONS: There is likely a correlation between contused lung volume and risk of pulmonary complications; dichotomously classifying pulmonary contusions is insufficient. Better understanding this correlation requires establishing the clinically significant contusion volume and a correspondingly refined classification system.

Measurement of local diffusion and composition in degraded articular cartilage reveals the unique role of surface structure in controlling macromolecular transport.

Developing effective therapeutics for osteoarthritis (OA) necessitates that such molecules can reach and target chondrocytes within articular cartilage. However, predicting how well very large therapeutic molecules diffuse through cartilage is often difficult, and the relationship between local transport mechanics for these molecules and tissue heterogeneities in the tissue is still unclear. In this study, a 150 kDa antibody diffused through the articular surface of healthy and enzymatically degraded cartilage, which enabled the calculation of local diffusion mechanics in tissue with large compositional variations. Local cartilage composition and structure was quantified with Fourier transform infrared (FTIR) spectroscopy and second harmonic generation (SHG) imaging techniques. Overall, both local concentrations of aggrecan and collagen were correlated to local diffusivities for both healthy and surface-degraded samples (0.3 > R2 < 0.9). However, samples that underwent surface degradation by collagenase exhibited stronger correlations (R2 > 0.75) compared to healthy samples (R2 < 0.46), suggesting that the highly aligned collagen at the surface of cartilage acts as a barrier to macromolecular transport.