Don’t call me in the morning: why it might be best to see patients in-person, a case report

Case Diagnosis: Post-irradiation Sarcoma Case Description: A 58-year-old woman with a history of stage IIIB squamous cell carcinoma of the cervix who was treated with chemoradiation, considered in remission 5 years prior on PET CT, and was under every 6-months surveillance for recurrence by gynecology. She presented to the Emergency Department for severe back pain, left sided sciatica, and paresthesias. In the absence of fracture or cord compression, she was discharged with recommendations for primary care follow-up. This took place over the telephone with referral to the spine center. One week later, her pain progressed to 10+/10 with dense left leg numbness, and multiple falls. Physiatry ordered a lumbar MRI for focal neurologic findings on exam, which revealed a large destructive lesion of the left ilium and left hemisacrum with soft tissue extension. This was later determined to be undifferentiated sarcoma, likely due to prior radiation. She is currently undergoing palliative chemotherapy. Discussions: Post-irradiation sarcomas (PIS) are a relatively rare event and exhibit dose dependency. Sarcomas can present with bone pain that can be worse at night and signs and symptoms of compression of surrounding structures. The pelvis is a common site for sarcoma development. Cases of PIS have presented in even just a few months post radiation therapy. The prognosis of patients with PIS is poorer than those with primary sarcomas. This patient would require hemipelvectomy to attempt curative treatment. Conclusions: PIS are typically aggressive, have poor prognosis, and can develop within months of high doses of radiation therapies; clinicians index of suspicion for sarcomas in patients with a history of radiation must be high. Evaluation for progressive pain, weakness, and numbness may not be amenable to telemedicine until technology improves. Patients that present with signs and symptoms of progressive nerve compression and bone pain should be re-examined early on

White matter signal abnormalities in former National Football League players

Introduction: Later-life brain alterations in former tackle football players are poorly understood, particularly regarding their relationship with repetitive head impacts (RHIs) and clinical function. We examined white matter signal abnormalities (WMSAs) and their association with RHIs and clinical function in former National Football League (NFL) players. Methods: Eighty-six clinically symptomatic former NFL players and 23 same-age reportedly asymptomatic controls without head trauma exposure underwent magnetic resonance imaging and neuropsychological testing. FreeSurfer calculated WMSAs. A cumulative head impact index quantified RHIs. Results: In former NFL players, increased volume of WMSAs was associated with higher cumulative head impact index scores (P = .043) and worse psychomotor speed and executive function (P = .015). Although former NFL players had greater WMSA volume than controls (P = .046), these findings are inconclusive due to recruitment of controls based on lack of clinical symptoms and head trauma exposure. Discussion In former NFL players, WMSAs may reflect long-term microvascular and nonmicrovascular pathologies from RHIs that negatively impact cognition

Magnetic Resonance Spectroscopy as a Biomarker for Chronic Traumatic Encephalopathy

AbstractChronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHI). Currently, CTE can only be diagnosed after death by postmortem, as validated in vivo biomarkers of CTE do not yet exist. Proton magnetic resonance spectroscopy (MRS) measures brain tissue metabolism in vivo and could facilitate a “probable CTE” diagnosis during life. Here, we propose MRS as one potential biomarker for CTE through a review of CTE neuropathology, and the extant literature that has examined the acute and long-term effects of RHI exposure on brain chemistry. There is preliminary empirical support for MRS in the detection of later-life neurological impairment associated with RHI exposure, but further ante- and postmortem research is needed before MRS can be considered a diagnostic biomarker for CTE.</jats:p

Repetitive head impact exposure and later-life plasma total tau in former National Football League players

Introduction: Blood protein analysis of total tau (t-tau) may be a practical screening biomarker for chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. We examined plasma t-tau in symptomatic former National Football League (NFL) players compared with controls and the relationship between RHI exposure and later-life plasma t-tau. Methods: Ninety-six former NFL players (age 40–69) and 25 same-age controls underwent blood draw to determine plasma t-tau levels. The cumulative head impact index (CHII) quantified RHI exposure. Subjects completed measures of clinical function. Results: A higher CHII predicted greater plasma t-tau in the former NFL players (P = .0137). No group differences in plasma t-tau emerged, but a concentration ≥3.56 pg/mL was 100% specific to former NFL players. Plasma t-tau did not predict clinical function. Discussion Greater RHI exposure predicted higher later-life plasma t-tau concentrations, and further study on plasma t-tau as a candidate screening biomarker for CTE is warranted

Multi-Center Analysis of Liver Transplantation for Combined Hepatocellular Carcinoma-Cholangiocarcinoma Liver Tumors.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma liver tumors (cHCC-CCA) with pathologic differentiation of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma within the same tumor are not traditionally considered for liver transplantation due to perceived poor outcomes. Published results are from small cohorts and single centers. Through a multi-center collaboration, we performed the largest analysis to date of the utility of liver transplantation for cHCC-CCA. STUDY DESIGN: Liver transplant and resection outcomes for HCC (n=2998) and cHCC-CCA (n=208) were compared in a 12-center retrospective review (2009-2017). Pathology defined tumor type. Tumor burden was based on radiologic Milan criteria at time of diagnosis and applied to cHCC-CCA for uniform analysis. Kaplan-Meier survival curves and log-rank test were used to determine overall survival and disease-free survival. Cox regression was used for multivariate survival analysis. RESULTS: Liver transplant for cHCC-CCA (n=67) and HCC (n=1814) within Milan had no significant difference in overall survival (5-yr cHCC-CCA 70.1%, HCC 73.4%, p=0.806) despite higher cHCC-CCA recurrence rates (23.1% vs 11.5% 5-years, p CONCLUSIONS: Regardless of tumor burden, outcomes following liver transplant are superior to resection for patients with cHCC-CCA. Within Milan criteria, liver transplant for cHCC-CCA and HCC results in similar overall survival justifying consideration of transplantation due to the higher chance of cure with liver transplantation in this traditionally excluded population

Leveraging football accelerometer data to quantify associations between repetitive head impacts and chronic traumatic encephalopathy in males

Abstract Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impacts (RHI), but the components of RHI exposure underlying this relationship are unclear. We create a position exposure matrix (PEM), composed of American football helmet sensor data, summarized from literature review by player position and level of play. Using this PEM, we estimate measures of lifetime RHI exposure for a separate cohort of 631 football playing brain donors. Separate models examine the relationship between CTE pathology and players’ concussion count, athletic positions, years of football, and PEM-derived measures, including estimated cumulative head impacts, linear accelerations, and rotational accelerations. Only duration of play and PEM-derived measures are significantly associated with CTE pathology. Models incorporating cumulative linear or rotational acceleration have better model fit and are better predictors of CTE pathology than duration of play or cumulative head impacts alone. These findings implicate cumulative head impact intensity in CTE pathogenesis