Combination immune checkpoint inhibitor-induced hypophysitis: A case report

Background: Immune checkpoint inhibitors have emerged as a promising new class of anti-cancer drugs. Unfortunately, while potentiating the immune system’s response to cancer cells, these drugs also place the patient at risk for the development of immune-related adverse events. Although most commonly involving the gastrointestinal tract and skin, involvement of the endocrine system also occurs, with hypophysitis one of the most frequent complications. This case report describes a case of immune checkpoint inhibitor-induced hypophysitis in a patient with metastatic melanoma undergoing combination therapy, and the associated imaging findings. Case Report: A 60-year-old male undergoing combination immune checkpointtherapy with nivolumab (an anti-PD-1 antibody) and ipilimumab (an anti-CTLA-4 antibody)formetastatic melanoma developed headaches. An MRI of the brain was obtained and demonstrated new enlargement of the pituitary. The patient was also found to be hypothyroid. Further endocrinological evaluation revealed low testosterone, low random cortisol level, and low TSH, consistent with pituitary insufficiency. At this time, the checkpoint inhibitor therapy was held and the patient was treated with prednisone with excellent clinical response, including resolved headaches and improved energy. Follow-up MRI demonstrated resolution of the pituitary enlargement. Imaging Findings: Sagittal pre-contrast MR images demonstrate a normal appearance of the pituitary prior to initiation of the combination checkpoint inhibitor therapy and interval enlargement of the pituitary approximately three months later near the end of the combination therapy. A sagittal post-contrast MR image following checkpoint inhibitor therapy discontinuation and steroid treatment demonstrates near resolution of the pituitary enlargement. Conclusion: As new cancer therapies emerge, physicians must remain aware of the potential for unique adverse effects – such as those occurring with immune checkpoint inhibitor therapies, including hypophysitis. In addition, as the imaging appearance of hypophysitis is not specific, understanding the clinical context in which it occurs can aid radiologists in recognizing it as a possible diagnosis and help guide appropriate clinical management.https://scholarlycommons.henryford.com/merf2019caserpt/1079/thumbnail.jp

Creating a Comprehensive Navigation Documentation Tool to Improve Reporting

Introduction and Context: Inconsistent data collection and reporting is one of the biggest threats to supporting a navigation program 1. Quality data is used to capture navigation outcomes that emphasize the importance and support expansion of navigation programs. Previous documentation at Levine Cancer (LC) and Wake Forest Baptist (WFB) was limited and most of the information was documented in narrative form. Oncology programs at LC and WFB integrated, requiring navigation teams to create a new shared documentation tool that would capture detailed and measurable data to enhance outcome reporting. Implementation Strategy: Representatives from LC and WFB met routinely to merge documentation tools. Comprehensive flowsheets with discrete data fields were adapted to capture a barrier and needs assessment, acuity level, referrals made, education performed, type of contact, and the time spent with each patient. Once the tools were merged, LC and WFB met with the Information Systems team to build the documentation flowsheet and provide a data reporting framework. Outcomes and Impact: Previous reports for documentation across sites had limitations and varied in the number of data elements. The new documentation tool provides multiple flowsheets that allow collection of extensive information about patient\u27s barriers and needs and interventions performed by the navigator, which is now utilized by over 50 nurse and patient navigators. Development of flowsheets with discrete fields makes data collection and reporting more reliable and accurate. These discrete fields also maximize data completeness and standardized structure2. Insights: By creating a concise and thorough way to collect information in the EMR, it is readily available, accessible, consistent, and allows for better workflow. Streamlining this information provides site-specific trends and allows for larger evaluation, research, and outcome reporting. Implications: Future plans include further adaptation to additional forms of navigation, such as screening navigation. Flowsheet data will also support establishing navigation as a reimbursable service in the future3. References Battaglia, T., Fleisher, L., Dwyer, A., Wiatrek, D., Well, K., Wightman, P., Strusowski, T., & Calhoun, E. (2022). Barriers and opportunities to measuring oncology patient navigation impact: Results from the National Navigation Roundtable survey. Cancer, 128, 2568-2577. https://doi.org/10.1002/cncr.33805 Bush, R., Kuelbs, C., Ryu, J., Jian., W., & Chiang, G. (2017). Structured data entry in the electronic medical record: Perspectives of pediatric specialty physicians and surgeons. Journal of Medical Systems, 41(5), 75. https://doi.org/10.1007%2Fs10916-017-0716-5 Garfield, K., Franklin, E., Battaglia, T., Dwyer, A., Freund, K., Wightman, P., & Rohan, E. (2022). Evaluating the sustainability of patient navigation programs in oncology by length of existence, funding, and payment model participation. Cancer, 128(513), 2758-2589. https://doi.org/10.1002/cncr.3393

Diagnostic Utility of a Ferritin-to-Procalcitonin Ratio to Differentiate Patients With COVID-19 From Those With Bacterial Pneumonia: A Multicenter Study

Background: There is an urgent need for accurate, rapid, inexpensive biomarkers that can differentiate coronavirus disease 2019 (COVID-19) from bacterial pneumonia. We assess the role of the ferritin-to-procalcitonin (F/P) ratio to classify pneumonia cases into those due to COVID-19 vs those due to bacterial pathogens. Methods: This multicenter case-control study compared patients with COVID-19 with those with bacterial pneumonia, admitted between March 1 and May 31, 2020. Patients with COVID-19 and bacterial pneumonia co-infection were excluded. The F/P in patients with COVID-19 vs with bacterial pneumonia were compared. Receiver operating characteristic curve analysis determined the sensitivity and specificity of various cutoff F/P values for COVID-19 vs bacterial pneumonia. Results: A total of 242 COVID-19 pneumonia cases and 34 bacterial pneumonia controls were included. Patients with COVID-19 pneumonia had a lower mean age (57.1 vs 64.4 years; P = .02) and a higher body mass index (30.74 vs 27.15 kg/m2; P = .02) compared with patients with bacterial pneumonia. Cases and controls had a similar proportion of women (47% vs 53%; P = .5), and COVID-19 patients had a higher prevalence of diabetes mellitus (32.6% vs 12%; P = .01). The median F/P was significantly higher in patients with COVID-19 (4037.5) compared with the F/P in bacterial pneumonia (802; P < .001). An F/P ≥877, used to diagnose COVID-19, resulted in a sensitivity of 85% and a specificity of 56%, with a positive predictive value of 93.2% and a likelihood ratio of 1.92. In multivariable analyses, an F/P ≥877 was associated with greater odds of identifying a COVID-19 case (odds ratio, 11.27; 95% CI, 4-31.2; P < .001). Conclusions: An F/P ≥877 increases the likelihood of COVID-19 pneumonia compared with bacterial pneumonia. © 2021 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America

Increasing Dietary Fat Elicits Similar Changes in Fat Oxidation and Markers of Muscle Oxidative Capacity in Lean and Obese Humans

In lean humans, increasing dietary fat intake causes an increase in whole-body fat oxidation and changes in genes that regulate fat oxidation in skeletal muscle, but whether this occurs in obese humans is not known. We compared changes in whole-body fat oxidation and markers of muscle oxidative capacity differ in lean (LN) and obese (OB) adults exposed to a 2-day high-fat (HF) diet. Ten LN (BMI = 22.5±2.5 kg/m2, age = 30±8 yrs) and nine OB (BMI = 35.9±4.93 kg/m2, 38±5 yrs, Mean±SD) were studied in a room calorimeter for 24hr while consuming isocaloric low-fat (LF, 20% of energy) and HF (50% of energy) diets. A muscle biopsy was obtained the next morning following an overnight fast. 24h respiratory quotient (RQ) did not significantly differ between groups (LN: 0.91±0.01; OB: 0.92±0.01) during LF, and similarly decreased during HF in LN (0.86±0.01) and OB (0.85±0.01). The expression of pyruvate dehydrogenase kinase 4 (PDK4) and the fatty acid transporter CD36 increased in both LN and OB during HF. No other changes in mRNA or protein were observed. However, in both LN and OB, the amounts of acetylated peroxisome proliferator-activated receptor γ coactivator-1-α (PGC1-α) significantly decreased and phosphorylated 5-AMP-activated protein kinase (AMPK) significantly increased. In response to an isoenergetic increase in dietary fat, whole-body fat oxidation similarly increases in LN and OB, in association with a shift towards oxidative metabolism in skeletal muscle, suggesting that the ability to adapt to an acute increase in dietary fat is not impaired in obesity

Biofluid Biomarkers in Huntington's Disease

Huntington's disease (HD) is a chronic progressive neurodegenerative condition where new markers of disease progression are needed. So far no disease-modifying interventions have been found, and few interventions have been proven to alleviate symptoms. This may be partially explained by the lack of reliable indicators of disease severity, progression, and phenotype.Biofluid biomarkers may bring advantages in addition to clinical measures, such as reliability, reproducibility, price, accuracy, and direct quantification of pathobiological processes at the molecular level; and in addition to empowering clinical trials, they have the potential to generate useful hypotheses for new drug development.In this chapter we review biofluid biomarker reports in HD, emphasizing those we feel are likely to be closest to clinical applicability