The use of andexanet alfa vs. 4-factor prothrombin complex concentrates in the setting of life-threatening intracranial hemorrhage.

OBJECTIVE: Andexanet alfa is a targeted reversal agent for life threatening hemorrhage associated with direct acting oral anticoagulants (DOACs), but there is uncertainty regarding the benefit when compared to 4-factor prothrombin complex concentrate (4F-PCC) for this indication. We investigated the clinical outcomes and cost associated with reversal of DOACs in the setting of life-threatening intracranial hemorrhage (ICH). METHODS: A retrospective evaluation was conducted to evaluate patients with ICH in the setting of anticoagulation with DOAC from 9/1/2013 to 4/30/2020. Patients were included in the study if they received reversal with either andexanet alfa or 4F-PCC. RESULTS: Eighty-nine patients were included in the study. There was no statistically significant difference in 30-day mortality between patients who received andexanet alfa or 4F-PCC (52% vs. 35%, P  = 0.14). Radiographic stability of bleed was identified in 57% of patients receiving andexanet alfa vs. 58% of patients receiving 4F-PCC ( P  = 0.93). Median length of stay was not different between the andexanet alfa and 4F-PCC populations (7 days [IQR 6 - 12] vs. 6 days [IQR 3-12], P  = 0.66). Median cost of reversal agent was higher in patients receiving andexanet alfa compared to 4F-PCC ($15 000 [IQR 15 000-$27 000] vs. $11 650 [IQR $8567-$14 149]). CONCLUSION: Among patients with life-threatening intracranial hemorrhage in the setting of DOAC therapy, no clinical differences were observed with respect to selection of reversal agent. Prothrombin complex concentrates remain a viable alternative to reversal of DOAC therapy though multicenter, randomized, prospective studies are needed to further evaluate the role of 4F-PCC in the reversal of DOAC therapy.

Impact of ß-blockers on survival outcomes in patients with unresectable hepatocellular carcinoma.

Background: ß-blockers (BBs) have shown promise in improving overall survival (OS) in patients with breast, ovarian, pancreatic and lung cancer. However, few studies have evaluated the impact of BBs on unresectable hepatocellular carcinoma (HCC). Methods: The authors compared clinical data and outcomes between unresectable HCC patients based on whether they were prescribed BBs. Results: There was significantly decreased disease progression in the BB group compared with the non-BB group (22.8 vs 28.0%; p < 0.05). No difference was seen in OS or progression-free survival between groups. Those specifically on selective BBs had improved OS (hazard ratio: 0.75; 95% CI: 0.61-0.94; p = 0.01) and progression-free survival (hazard ratio: 0.66; 95% CI: 0.45-0.96; p = 0.03) compared with non-BB patients. Conclusion: Although the authors' study did not demonstrate that BBs improve OS in HCC, it did show decreased disease progression among patients with HCC who were taking BBs compared with those who were not.

Endocrine adherence in male versus female breast cancer: a seer-medicare review.

PURPOSE: Breast cancer in men (BC-M) is almost exclusively hormone receptor positive. We conducted a large review of the SEER-Medicare linked database to compare endocrine therapy adherence, discontinuation, and survival outcomes of male versus female patients with breast cancer. METHODS: Study data were obtained through the SEER-Medicare linked database. The study included patients age ≥ 65 years-old diagnosed with breast cancer between 2007 and 2015. The primary endpoints were rates of adherence and discontinuation of endocrine therapy (ET). Adherence was defined as a gap of less than 90 days in-between consecutive Medicare prescriptions. Discontinuation was defined as a gap of greater than 12 months in-between Medicare prescriptions. Secondary endpoint was the association of use of ET with overall survival (OS). RESULTS: Of the 363 male patients on ET, 214 patients (59.0%) were adherent to the therapy, and 149 patients (41.0%) were nonadherent. Of the 20,722 females on ET, 10,752 (51.9%) were adherent to the therapy, and 9970 (48.1%) were nonadherent. 39 male patients (10.7%) discontinued therapy, while 324 (89.3%) did not discontinue therapy. 1849 female patients (8.9%) discontinued therapy, while 18,873 (91.1%) patients did not. Men were significantly more adherent than women (p = 0.008), but there was no significant difference in discontinuation among men and women (p = 0.228). Survival was significantly improved in both men (HR 0.77, 95% CI 0.60-0.99, p = 0.039) and women (HR 0.84, 95% CI 0.81-0.87, p < 0.001) on ET. CONCLUSION: Identification of contributing factors impacting adherence and discontinuation is needed to allow physicians to address barriers to long term use of ET.

Extramedullary Hematopoiesis in Mismatch Repair Deficient Colon Cancer Patient on Adjuvant Chemotherapy.

A 59-year-old male presented with a two-month history of abdominal pain and was found to have an obstructing cecal mass. Colonoscopy and biopsy confirmed invasive adenocarcinoma. Immunohistochemical analyses for mismatch repair (MMR) proteins revealed the loss of MLH1 as well as PMS2 in cancerous nuclei, which makes the tumor MMR deficient. Negative germline testing for MMR proteins ruled out the Lynch syndrome. After negative staging computerized tomography scan for distant metastases, he underwent ileocolectomy with ileotransverse colonic anastomosis. Final pathological analysis revealed poorly differentiated adenocarcinoma with signet ring features, negative margins, and 3/22 lymph nodes positive, classified as stage IIIB (T4aN1bM0). Adjuvant chemotherapy with modified FOLFOX (leucovorin calcium/folinic acid, fluorouracil, and oxaliplatin) was started without the use of any growth factor support. After cycle 9 of 12, he developed mild transaminitis, carcinoembryonic antigen elevation, and interval development of two heterogeneously enhancing hepatic lesions. Biopsy of both of these lesions revealed extramedullary hematopoiesis (EMH), with no evidence of metastatic disease. He completed adjuvant chemotherapy without complication, and these liver lesions have decreased in size during the follow-up period of almost two years thus far. EMH is extremely rare in patients with colon cancer. Contributing factors include therapy-specific (growth factor support), bone marrow suppression secondary to chemotherapy and radiation therapy, and tumor-specific factors (cytokine and growth factors released by the tumor). To the best of our knowledge, this is the first case report of EMH in an MMR deficient colon cancer patient on adjuvant FOLFOX. MMR-deficient tumors show signs of a high degree of infiltration with CD8+ cytotoxic T lymphocytes as well as helper T cells, leading to increased production of cytokines, such as interferon-γ. This could be a potential etiology behind EMH in our patient who was MMR deficient. The role of the MMR-deficient state in the development of EMH should be explored further.

The effects of hyperglycemia on outcomes in surgical high-grade glioma patients.

OBJECTIVE: To define the glucose values associated with an increase in complication rates in post-operative brain tumor patients. PATIENTS AND METHODS: Patients who underwent craniotomy for resection of WHO Grade III or IV glioma from 2011 to 2014 were retrospectively reviewed. Post-operative blood glucose values were recorded for post-operative day #0, #1, and #2. Medians were obtained and assessed for significance. Multivariate analysis was performed to assess patient demographics, pre-operative findings, steroid use, and blood glucose values with respect to post-operative complications and to 30-day readmission. RESULTS: 108 patients underwent craniotomy for resection of high-grade glioma and had postoperative blood glucose values documented. Median blood glucose values greater than 167 mg/dL were associated with increased serious post-operative complications, and values greater than 163 mg/dL were associated with increased 30-day readmissions. CONCLUSION: Post-operative hyperglycemia in patients with high-grade gliomas places this vulnerable patient population to undue post-operative complications and readmissions, potentially delaying further treatment of their disease.

The effects of new or worsened postoperative neurological deficits on survival of patients with glioblastoma.

OBJECTIVE An increased extent of resection (EOR) has been shown to improve overall survival of patients with glioblastoma (GBM) but has the potential for causing a new postoperative neurological deficit. To investigate the impact of surgical neurological morbidity on survival, the authors performed a retrospective analysis of the clinical data from patients with GBM to quantify the impact of a new neurological deficit on the survival benefit achieved with an increased EOR. METHODS The data from all GBM patients who underwent resection at the University of Florida from 2010 to 2015 with postoperative imaging within 72 hours of surgery were included in the study. Retrospective analysis was performed on clinical outcomes and tumor volumes determined on postoperative and follow-up imaging examinations. RESULTS Overall, 115 patients met the inclusion criteria for the study. Tumor volume at the time of presentation was a median of 59 cm3 (enhanced on T1-weighted MRI scans). The mean EOR (± SD) was 94.2% ± 8.7% (range 59.9%-100%). Almost 30% of patients had a new postoperative neurological deficit, including motor weakness, sensory deficits, language difficulty, visual deficits, confusion, and ataxia. The neurological deficits had resolved in 41% of these patients on subsequent follow-up examinations. The median overall survival was 13.1 months (95% CI 10.9-15.2 months). Using a multipredictor Cox model, the authors observed that increased EOR was associated with improved survival except for patients with smaller tumor volumes (≤ 15 cm3). A residual volume of 2.5 cm3 or less predicted a favorable overall survival. Developing a postoperative neurological deficit significantly affected survival (9.2 months compared with 14.7 months, p = 0.02), even if the neurological deficit had resolved by the first follow-up. However, there was a trend of improved survival among patients with resolution of a neurological deficit by the first follow-up compared with patients with a permanent neurological deficit. Any survival benefit from achieving a 95% EOR was abrogated by the development of a new neurological deficit postoperatively. CONCLUSIONS Developing a new neurological deficit after resection of GBM is associated with a decrease in overall survival. A careful balance between EOR and neurological compromise needs to be taken into account to reduce the likelihood of neurological morbidity from surgery.