Lymph node dissection after neoadjuvant chemotherapy improves overall survival in clinical stage III endometrial cancer.

OBJECTIVE: To investigate whether performing a lymph node dissection during hysterectomy improves overall survival in patients with clinical stage III endometrial cancer who received neoadjuvant chemotherapy. METHODS: The National Cancer Database was queried to identify all patients with clinical stage III endometrial cancer who had undergone pre-operative chemotherapy as first course of treatment followed by hysterectomy with or without lymph node dissection between the years 2004 and 2020. Univariable and multivariable models were performed to investigate prognostic factors on overall survival. RESULTS: This study analyzed 2882 patients with clinical stage III endometrial cancer who received upfront chemotherapy. Among those who underwent lymph node dissection, 38% had positive lymph nodes. Factors found to be independently associated with improved survival included lymph node dissection (p<0.001), adjuvant radiation (p<0.001), histology (p<0.001), tumor grade (p<0.001), pathologic node status (p<0.001), age (p<0.001), type of insurance (p=0.027), and race (p<0.001). Patients who underwent lymph node dissection at time of hysterectomy had a significantly better overall survival (107 vs 85 months; p<0.001). Multivariate and propensity score analyses robustly demonstrated that lymph node dissection significantly improved overall survival (HR 0.69, 95% CI 0.57 to 0.84, p<0.001), even among patients with pathologically negative lymph nodes. CONCLUSION: Our study suggests that performing lymph node dissection at the time of hysterectomy is associated with improved overall survival in all patients with stage III endometrial cancer who receive upfront chemotherapy, regardless of age, race, insurance status, histologic subtype, tumor grade, pathologic node status, adjuvant radiation or chemotherapy. Notably, patients with high-risk disease may particularly benefit from this approach.

Immunogenicity of 2-Dose HPV Vaccine Series for Postpartum Women: An Open-Label, Nonrandomized, Noninferiority Trial.

Importance: Postpartum human papillomavirus (HPV) vaccination is a promising strategy to increase HPV vaccination uptake in the US, particularly for reaching vaccine-naive women and those who lack health insurance beyond the pregnancy period. However, completion of the 3-dose vaccine regimen is challenging. Objective: To evaluate the immunogenicity of a 2-dose postpartum HPV vaccination regimen (0 and 6 months) and assess whether it is noninferior to a 3-dose postpartum HPV vaccination regimen (0, 1-2, and 6 months) administered to historical controls. Design, Setting, and Participants: A noninferiority, open-label, nonrandomized immunogenicity trial was conducted from August 4, 2020, to June 23, 2022, of postpartum patients aged 15 to 45 years who delivered at 2 hospitals in Baltimore, Maryland. Historical controls were adolescents and young women aged 16 to 26 years. Intervention: Two doses of the nonavalent HPV vaccine administered 6 months apart. Main Outcomes and Measures: The primary outcome was noninferiority (90% CI, lower bound >0.67) of the geometric mean titer (GMT) ratio for HPV-16 among postpartum women compared with historical controls. Secondary outcomes were noninferiority of GMT ratios for the other 8 HPV types and percentage seroconversion for each HPV type. As a noninferiority trial, the primary analysis used the per-protocol analysis. Results: Of 225 enrolled participants, the mean (SD) age at baseline was 29.9 (6.8) years, and 171 (76.0%) were HPV-16 seronegative at baseline. Of these 171 participants, 129 (75.4%) received a second vaccine dose and completed the subsequent 4-week serologic measurements. Relative to historical controls, the HPV-16 GMT ratio was 2.29 (90% CI, 2.03-2.58). At month 7, HPV-16 GMT was higher after the 2-dose regimen (7213.1 mMU/mL [90% CI, 6245.0-8331.4 mMU/mL]) than among historic controls after the 3-dose regimen (3154.0 mMU/mL [90% CI, 2860.2-3478.0 mMU/mL]). Similarly, the lower bound of the 90% CI of the GMT ratio was above 1 for the 8 HPV types 6, 11, 18, 31, 33, 45, 52, and 58. A total of 118 of 134 women (88.1%) seroconverted for HPV-16 after the first dose; 4 weeks after the second dose, the seroconversion rate was 99% or greater for all HPV types. Conclusions and Relevance: This study suggests that immunogenicity of a 2-dose HPV vaccination regimen given 6 months apart among postpartum women was noninferior to a 3-dose regimen among young historical controls. Most women seroconverted after the first dose of the 2-dose regimen. These results demonstrate that postpartum vaccination using a reduced schedule may be a promising strategy to increase HPV vaccine series completion. Trial Registration: ClinicalTrials.gov Identifier: NCT04274153.

Severe hypertriglyceridemia during treatment with intraperitoneal cisplatin and paclitaxel for advanced stage fallopian tube carcinoma.

This case report describes a patient who developed severe hypertriglyceridemia (1871 mg/dL) and hyperlipidemia (LDL 132 mg/dL) during intraperitoneal (IP) administration of cisplatin and paclitaxel as adjuvant treatment for stage IIIC fallopian tube carcinoma. After an evaluation with her primary care physician, she was treated with gemfibrozil and rosuvastatin for the duration of her treatment. There was complete resolution of hypertriglyceridemia after completion of chemotherapy. This adverse event is rare and has not been reported in the literature with this chemotherapeutic regimen. A pre-chemotherapy evaluation for dyslipidemia may be beneficial in the detection and monitoring of this condition.

Multimodality Monitoring in Neurocritical Care: Decision-Making Utilizing Direct And Indirect Surrogate Markers.

Substantial progress has been made to create innovative technology that can monitor the different physiological characteristics that precede the onset of secondary brain injury, with the ultimate goal of intervening prior to the onset of irreversible neurological damage. One of the goals of neurocritical care is to recognize and preemptively manage secondary neurological injury by analyzing physiologic markers of ischemia and brain injury prior to the development of irreversible damage. This is helpful in a multitude of neurological conditions, whereby secondary neurological injury could present including but not limited to traumatic intracranial hemorrhage and, specifically, subarachnoid hemorrhage, which has the potential of progressing to delayed cerebral ischemia and monitoring postneurosurgical interventions. In this study, we examine the utilization of direct and indirect surrogate physiologic markers of ongoing neurologic injury, including intracranial pressure, cerebral blood flow, and brain metabolism.

Low Glasgow Coma Score in Traumatic Intracranial Hemorrhage Predicts Development of Cerebral Vasospasm.

BACKGROUND: The exact mechanism, incidence, and risk factors for cerebral vasospasm after traumatic intracranial hemorrhage (ICH) continue to be poorly characterized. The incidence of post-traumatic vasospasm (PTV) varies depending on the detection modality. OBJECTIVE: We aimed to shed light on the predictors, associations, and true incidence of cerebral vasospasm after traumatic ICH using digital subtraction angiography (DSA) as the gold standard. METHODS: We examined a prospectively maintained database of traumatic brain injury (TBI) patients to identify patients with ICH secondary to TBI enrolled between 2002 and 2015 at our trauma center. Patients with TBI-associated ICH and evidence of elevated velocities on transcranial Doppler and computed tomography angiograms, confirmed with DSA were included. The diagnostic cerebral angiograms were evaluated by 2 blinded neurointerventionalists for cerebral vasospasm. Statistical analyses were conducted to determine predictors of PTV. RESULTS: Twenty patients with ICH secondary to TBI and evidence of vasospasm underwent DSAs. Seven patients (7/20; 35%) with traumatic ICH developed cerebral vasospasm and of those, 1 developed delayed cerebral ischemia (1/7; 14%). Of these 7 patients, 6 presented with subarachnoid hemorrhage (6/7; 85%). Vasospasm was substantially more common in patients with a Glasgow Coma Scale <9 (P = 0.017) than in all other groups. CONCLUSIONS: PTV as demonstrated by DCA may be more common than previously reported. Patients who exhibit PTV were more likely to have a Glasgow Coma Scale <9. This subgroup of patients may benefit from more systematic screening for the development of PTV, and earlier monitoring for signs of delayed cerebral ischemia.

Novel minimally invasive multi-modality monitoring modalities in neurocritical care.

Elevated intracranial pressure (ICP) following brain injury contributes to poor outcomes for patients, primarily by reducing the caliber of cerebral vasculature, and thereby reducing cerebral blood flow. Careful monitoring of ICP is critical in these patients in order to determine prognosis, implement treatment when ICP becomes elevated, and to judge responsiveness to treatment. Currently, the gold standard for monitoring is invasive pressure transducers, usually an intraventricular monitor, which presents significant risk of infection and hemorrhage. These risks made discovering non-invasive methods for monitoring ICP and cerebral perfusion a priority for researchers. Herein we sought to review recent publications on novel minimally invasive multi-modality monitoring techniques that provide surrogate data on ICP, cerebral oxygenation, metabolism and blood flow. While limitations in various forms preclude them from supplanting the use of invasive monitors, these modalities represent useful screening tools within our armamentarium that may be invaluable when the risks of invasive monitoring outweigh the associated benefits.

Traumatic brain injury and intracranial hemorrhage-induced cerebral vasospasm: a systematic review.

OBJECTIVE Little is known regarding the natural history of posttraumatic vasospasm. The authors review the pathophysiology of posttraumatic vasospasm (PTV), its associated risk factors, the efficacy of the technologies used to detect PTV, and the management/treatment options available today. METHODS The authors performed a systematic review in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the following databases: PubMed, Google Scholar, and CENTRAL (the Cochrane Central Register of Controlled Trials). Outcome variables extracted from each study included epidemiology, pathophysiology, time course, predictors of PTV and delayed cerebral ischemia (DCI), optimal means of surveillance and evaluation of PTV, application of multimodality monitoring, modern management and treatment options, and patient outcomes after PTV. Study types were limited to retrospective chart reviews, database reviews, and prospective studies. RESULTS A total of 40 articles were included in the systematic review. In many cases of mild or moderate traumatic brain injury (TBI), imaging or ultrasonographic studies are not performed. The lack of widespread assessment makes finding the true overall incidence of PTV a difficult endeavor. The clinical consequences of PTV are important, given the morbidity that can result from it. DCI manifests as new-onset neurological deterioration that occurs beyond the timeframe of initial brain injury. While there are many techniques that attempt to diagnose cerebral vasospasm, digital subtraction angiography is the gold standard. Some predictors of PTV include SAH, intraventricular hemorrhage, low admission Glasgow Coma Scale (GCS) score (< 9), and young age (< 30 years). CONCLUSIONS Given these results, clinicians should suspect PTV in young patients presenting with intracranial hemorrhage (ICH), especially SAH and/or intraventricular hemorrhage, who present with a GCS score less than 9. Monitoring and regulation of CNS metabolism following TBI/ICH-induced vasospasm may play an important adjunct role to the primary prevention of vasospasm.