Mode of Delivery and Obstetric Complications in the Setting of Prior Uterine Surgery.

OBJECTIVE: This study aimed to evaluate cesarean rates and risk for obstetric complications among deliveries with a history of prior uterine surgery. STUDY DESIGN: This serial cross-sectional study analyzed deliveries with and without prior uterine surgery in the 2016-2019 Nationwide Inpatient Sample. Unadjusted and adjusted logistic regression models were performed to assess risk of nontransfusion severe maternal morbidity (SMM) and other obstetric complications based on the presence or absence of prior uterine surgery with unadjusted and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) as measures of association. Adjusted models accounted for demographic, hospital, and delivery factors. Demographics and clinical factors among deliveries with and without a prior history of uterine surgery diagnosis were compared with the chi-square test with p < 0.05 considered statistically significant. RESULTS: Of 14.7 million delivery hospitalization identified, 6,910 (4.7 per 10,000) had a history of uterine surgery and 111,710 (0.76%) experienced SMM. Women with prior uterine surgery were more likely to be older, to be of unknown race or ethnicity, and to have private insurance (p < 0.01 for all). Eighty-five percent of deliveries with prior uterine surgery were performed by cesarean compared with 32% of deliveries without prior uterine surgery (p < 0.01). In adjusted analysis, compared with patients without prior uterine surgery, patients with prior uterine surgery were not at increased risk for SMM (aOR 1.23, 95% CI 0.73-2.07). Evaluating obstetric complications, patients with prior uterine surgery had a decreased risk of postpartum hemorrhage (aOR 0.64, 95% CI 0.43-0.96) and an increased risk of peripartum hysterectomy (aOR 4.12, 95% CI 1.75-9.67), and no difference in other obstetric complications assessed. CONCLUSION: These findings suggest that current clinical practice results in similar delivery risks among patients with compared with without prior uterine surgery. KEY POINTS: · Risk for most adverse outcomes is similar among patients with prior uterine surgery.. · Risk for peripartum hysterectomy was higher with prior uterine surgery.. · Risk for SMM was not higher with prior uterine surgery..

Racial and Ethnic Disparities in Peripartum Hysterectomy Risk and Outcomes.

OBJECTIVE: This study aimed to determine whether race and ethnicity contribute to risks associated with peripartum hysterectomy. STUDY DESIGN: This retrospective cross-sectional study utilized the 2000-2014 Nationwide Inpatient Sample to analyze risk of peripartum hysterectomy and associated severe maternal morbidity, mortality, surgical injury, reoperation, surgical-site complications, and mortality by maternal race and ethnicity. Race and ethnicity were categorized as non-Hispanic white, non-Hispanic black, Hispanic, other, and unknown. Multivariable log-linear regression models including patient, clinical, and hospital risk factors were performed with adjusted risk ratios (aRRs) and 95% confidence intervals (CIs). RESULTS: Of 59,854,731 delivery hospitalizations, there were 45,369 peripartum hysterectomies (7.6 per thousand). Of these, 37.8% occurred among non-Hispanic white, 13.9% among non-Hispanic black, and 22.8% among Hispanic women. In adjusted analyses, non-Hispanic black (aRR: 1.21, 95% CI: 1.17-1.29) and Hispanic women (aRR: 1.25, 95% CI: 1.22-1.29) were at increased risk of hysterectomy compared with non-Hispanic white women. Risk for severe morbidity was increased for non-Hispanic black (aRR: 1.25, 95% CI: 1.19-1.33), but not for Hispanic (aRR: 1.02, 95% CI: 0.97-1.07) women. Between these three groups, risk for intraoperative complications was highest among non-Hispanic white women, risk for reoperation was highest among Hispanic women, and risk for surgical-site complications was highest among non-Hispanic black women. Evaluating maternal mortality, non-Hispanic black women (RR: 3.83, 95% CI: 2.65-5.53) and Hispanic women (RR: 2.49, 95% CI: 1.74-3.59) were at higher risk than non-Hispanic white women. CONCLUSION: Peripartum hysterectomy and related complications other than death differed modestly by race. In comparison, mortality differentials were large supporting that differential risk for death in the setting of this high-risk scenario may be an important cause of disparities. KEY POINTS: · Peripartum hysterectomy and related complications differed modestly by race.. · Mortality differentials in the setting of peripartum hysterectomy were large.. · Failure to rescue may be an important cause of peripartum hysterectomy disparities..

Linking Transcriptomic and Imaging Data Defines Features of a Favorable Tumor Immune Microenvironment and Identifies a Combination Biomarker for Primary Melanoma.

Patients with resected stage II-III melanoma have approximately a 35% chance of death from their disease. A deeper understanding of the tumor immune microenvironment (TIME) is required to stratify patients and identify factors leading to therapy resistance. We previously identified that the melanoma immune profile (MIP), an IFN-based gene signature, and the ratio of CD8+ cytotoxic T lymphocytes (CTL) to CD68+ macrophages both predict disease-specific survival (DSS). Here, we compared primary with metastatic tumors and found that the nuclei of tumor cells were significantly larger in metastases. The CTL/macrophage ratio was significantly different between primary tumors without distant metastatic recurrence (DMR) and metastases. Patients without DMR had higher degrees of clustering between tumor cells and CTLs, and between tumor cells and HLA-DR+ macrophages, but not HLA-DR- macrophages. The HLA-DR- subset coexpressed CD163+CSF1R+ at higher levels than CD68+HLA-DR+ macrophages, consistent with an M2 phenotype. Finally, combined transcriptomic and multiplex data revealed that densities of CD8 and M1 macrophages correlated with their respective cell phenotype signatures. Combination of the MIP signature with the CTL/macrophage ratio stratified patients into three risk groups that were predictive of DSS, highlighting the potential use of combination biomarkers for adjuvant therapy. SIGNIFICANCE: These findings provide a deeper understanding of the tumor immune microenvironment by combining multiple modalities to stratify patients into risk groups, a critical step to improving the management of patients with melanoma.

Validation of Melanoma Immune Profile (MIP), a Prognostic Immune Gene Prediction Score for Stage II-III Melanoma.

PURPOSE: Biomarkers are needed to stratify patients with stage II-III melanoma for clinical trials of adjuvant therapy because, while immunotherapy is protective, it also confers the risk of severe toxicity. We previously defined and validated a 53-immune gene melanoma immune profile (MIP) predictive both of distant metastatic recurrence and of disease-specific survival (DSS). Here, we test MIP on a third independent population. EXPERIMENTAL DESIGN: A retrospective cohort of 78 patients with stage II-III primary melanoma was analyzed using the NanoString assay to measure expression of 53 target genes, and MIP score was calculated. Statistical analysis correlating MIP with DSS, overall survival, distant metastatic recurrence, and distant metastasis-free interval was performed using ROC curves, Kaplan-Meier curves, and standard univariable and multivariable Cox proportional hazards models. RESULTS: MIP significantly distinguished patients with distant metastatic recurrence from those without distant metastatic recurrence using ROC curve analysis (AUC = 0.695; P = 0.008). We defined high- and low-risk groups based on the cutoff defined by this ROC curve and find that MIP correlates with both DSS and overall survival by ROC curve analysis (AUC = 0.719; P = 0.004 and AUC = 0.698; P = 0.004, respectively). Univariable Cox regression reveals that a high-risk MIP score correlates with DSS (P = 0.015; HR = 3.2). CONCLUSIONS: MIP identifies patients with low risk of death from melanoma and may constitute a clinical tool to stratify patients with stage II-III melanoma for enrollment in clinical trials.

Correction to: The Role of Oncolytic Viruses in the Treatment of Melanoma.

A correction was made to a sentence in the original article to provide additional clarification in the "Other Oncolytic Viruses" section.

The Role of Oncolytic Viruses in the Treatment of Melanoma.

PURPOSE OF REVIEW: Oncolytic virotherapy is a new approach to the treatment of cancer and its success in the treatment of melanoma represents a breakthrough in cancer therapeutics. This paper provides a review of the current literature on the use of oncolytic viruses (OVs) in the treatment of melanoma. RECENT FINDINGS: Talimogene laherparepvec (T-VEC) is the first OV approved for the treatment of melanoma and presents new challenges as it enters the clinical setting. Several other OVs are at various stages of clinical and pre-clinical development for the treatment of melanoma. Reports from phase Ib-III clinical trials combining T-VEC with checkpoint blockade are encouraging and demonstrate potential added benefit of combination immunotherapy. OVs have recently emerged as a standard treatment option for patients with advanced melanoma. Several OVs and therapeutic combinations are in development. Immunooncolytic virotherapy combined with immune checkpoint inhibitors is promising for the treatment of advanced melanoma.

Predicting response to checkpoint inhibitors in melanoma beyond PD-L1 and mutational burden.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have changed the clinical management of melanoma. However, not all patients respond, and current biomarkers including PD-L1 and mutational burden show incomplete predictive performance. The clinical validity and utility of complex biomarkers have not been studied in melanoma. METHODS: Cutaneous metastatic melanoma patients at eight institutions were evaluated for PD-L1 expression, CD8+ T-cell infiltration pattern, mutational burden, and 394 immune transcript expression. PD-L1 IHC and mutational burden were assessed for association with overall survival (OS) in 94 patients treated prior to ICI approval by the FDA (historical-controls), and in 137 patients treated with ICIs. Unsupervised analysis revealed distinct immune-clusters with separate response rates. This comprehensive immune profiling data were then integrated to generate a continuous Response Score (RS) based upon response criteria (RECIST v.1.1). RS was developed using a single institution training cohort (n = 48) and subsequently tested in a separate eight institution validation cohort (n = 29) to mimic a real-world clinical scenario. RESULTS: PD-L1 positivity ≥1% correlated with response and OS in ICI-treated patients, but demonstrated limited predictive performance. High mutational burden was associated with response in ICI-treated patients, but not with OS. Comprehensive immune profiling using RS demonstrated higher sensitivity (72.2%) compared to PD-L1 IHC (34.25%) and tumor mutational burden (32.5%), but with similar specificity. CONCLUSIONS: In this study, the response score derived from comprehensive immune profiling in a limited melanoma cohort showed improved predictive performance as compared to PD-L1 IHC and tumor mutational burden.

Postoperative Myocardial Injury and Inflammation Is Not Blunted by a Trial of Atorvastatin in Orthopedic Surgery Patients.

BACKGROUND: Orthopedic patients are at risk for adverse postoperative cardiovascular outcomes. QUESTIONS/PURPOSES: This pilot randomized controlled trial (RCT) of atorvastatin vs. placebo in orthopedic surgery patients was performed in order to assess: (1) the prevalence of perioperative myocardial injury; (2) the effect of atorvastatin on perioperative inflammation; and (3) the feasibility of performing a large RCT of statin therapy in orthopedic patients. METHODS: Hip fracture (hip Fx) and total hip and knee replacement (THR and TKR) patients were randomized 1:1 to atorvastatin 40 mg daily vs. placebo, starting preoperatively and continuing until postoperative day (POD) 45. High-sensitivity cardiac troponin I (hs-cTnI), high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were measured preoperatively and on POD 2. Patients were monitored for adverse events until POD 90. RESULTS: Five hundred fifty-six patients were screened, 22 were recruited (4 hip Fx, 11 THR, 7 TKR), and 2 withdrew. Most (80%) had detectable hs-cTnI (> 1.1 pg/mL) preoperatively. Twenty percent had a perioperative rise in hs-cTnI (≥ 10 pg/mL), which was not blunted by atorvastatin. Hs-CRP rose in 19/20 patients, and IL-6 rose in all patients. However, atorvastatin did not blunt the rise in these inflammatory biomarkers. On POD 2, IL-6 and hs-cTnI levels correlated (ρ = 0.59, p = 0.02). Recruitment was limited by the high prevalence of statin use in the screened population and a high prevalence of exclusions among hip fracture patients. CONCLUSION: Perioperative myocardial injury and inflammation are common in orthopedic patients and do not appear to be reduced in those randomized to atorvastatin. TRIAL REGISTRATION: NCT02197065.

Disparities in TKA Outcomes: Census Tract Data Show Interactions Between Race and Poverty.

BACKGROUND: Race is an important predictor of TKA outcomes in the United States; however, analyses of race can be confounded by socioeconomic factors, which can result in difficulty determining the root cause of disparate outcomes after TKA. QUESTIONS/PURPOSES: We asked: (1) Are race and socioeconomic factors at the individual level associated with patient-reported pain and function 2 years after TKA? (2) What is the interaction between race and community poverty and patient-reported pain and function 2 years after TKA? METHODS: We identified all patients undergoing TKA enrolled in a hospital-based registry between 2007 and 2011 who provided 2-year outcomes and lived in New York, Connecticut, or New Jersey. Of patients approached to participate in the registry, more than 82% consented and provided baseline data, and of these patients, 72% provided 2-year data. Proportions of patients with complete followup at 2 years were lower among blacks (57%) than whites (74%), among patients with Medicaid insurance (51%) compared with patients without Medicaid insurance (72%), and among patients without a college education (67%) compared with those with a college education (71%). Our final study cohort consisted of 4035 patients, 3841 (95%) of whom were white and 194 (5%) of whom were black. Using geocoding, we linked individual-level registry data to US census tracts data through patient addresses. We constructed a multivariate linear mixed-effect model in multilevel frameworks to assess the interaction between race and census tract poverty on WOMAC pain and function scores 2 years after TKA. We defined a clinically important effect as 10 points on the WOMAC (which is scaled from 1 to 100 points, with higher scores being better). RESULTS: Race, education, patient expectations, and baseline WOMAC scores are all associated with 2-year WOMAC pain and function; however, the effect sizes were small, and below the threshold of clinical importance. Whites and blacks from census tracts with less than 10% poverty have similar levels of pain and function 2 years after TKA (WOMAC pain, 1.01 ± 1.59 points lower for blacks than for whites, p = 0.53; WOMAC function, 2.32 ± 1.56 lower for blacks than for whites, p = 0.14). WOMAC pain and function scores 2 years after TKA worsen with increasing levels of community poverty, but do so to a greater extent among blacks than whites. Disparities in pain and function between blacks and whites are evident only in the poorest communities; decreasing in a linear fashion as poverty increases. In census tracts with greater than 40% poverty, blacks score 6 ± 3 points lower (worse) than whites for WOMAC pain (p = 0.03) and 7 ± 3 points lower than whites for WOMAC function (p = 0.01). CONCLUSIONS: Blacks and whites living in communities with little poverty have similar patient-reported TKA outcomes, whereas in communities with high levels of poverty, there are important racial disparities. Efforts to improve TKA outcomes among blacks will need to address individual- and community-level socioeconomic factors. LEVEL OF EVIDENCE: Level III, therapeutic study.