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Background and objectives: Immune checkpoint inhibitor (ICI) use is increasing in the United States, real world data on acute kidney injury (AKI) in the expanding population are sparse. We evaluated trends in AKI incidence, and causes and management of AKI among 1914 persons receiving ICIs in a single center over a period of 5 years. Methods: We included all adults who received ICIs at the Stanford Healthcare System from July 1, 2015 to June 30, 2020. We defined AKI as an increase in serum creatinine to 1.5 times the baseline or an increase of ⩾0.3 mg/dL, and determined mean cumulative incidence of first and repeated episodes of AKI over three time periods. Results: Among the 1914 patients treated with ICIs, mean age was 64.9 (SD 14.3) years, 43% were women, 25% had baseline chronic kidney disease (CKD), 34% had lung and 23% had skin cancer as the indication. The overall cumulative incidence of any AKI and immune-related AKI at 1 year after initiating immunotherapy was 32% and 1.3% respectively. Among 586 cases of AKI, the most common cause was volume depletion (64%). Although 4% of AKI was immune-related, ICI therapy was discontinued in 14% of patients with AKI. Nephrology was consulted in 6%. The risk for AKI was higher among patients with a comorbidity index ⩾3 (vs CMI 0, HR 1.65 [95% CI 1.26–2.17]), digestive system cancer (vs skin cancer, 1.65 [1.13–2.43]), and lower baseline estimated glomerular filtration rate (30–59 and 60) (HR 1.69 [1.32–2.16] and 1.85 [1.16–2.97] respectively). Conclusions: AKI occurs in up to 1 in 3 patients, and 1 in 10 will have repeated episodes during the first year of ICI therapy. Incidence of AKI has remained similar over 5-year time span. The cause of AKI while on ICI is rarely an immune-related adverse event.

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.

BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe 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.ResultsICPi-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.ConclusionsPatients 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.

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 0.75) compared to healthy samples (R2

This study investigates the prevalence and potential etiologies of citation inaccuracies in surgical literature by systematically characterizing influential surgical articles and references they cited.

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.

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.