Research Spotlight

Raj, S., Ogola, G. and Han, J. (2021). “COVID-19 Vaccine-Associated Subclinical Axillary Lymphadenopathy on Screening Mammogram.” Acad Radiol Nov 17;S1076-6332(21)00538-9. [Epub ahead of print].

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BACKGROUND: Women who received a COVID-19 vaccination may display subclinical unilateral axillary lymphadenopathy on screening mammography, which can appear suspicious for malignancy, leading to additional diagnostic evaluation. PURPOSE: To evaluate the prevalence of subclinical unilateral axillary lymphadenopathy (sLAD) on screening mammogram in women who received either the first or second dose of the Pfizer-BioNTech (Pfizer) or Moderna COVID-19 vaccines compared to women who have not. MATERIALS AND METHODS: In this IRB-approved, HIPAA complaint study from 12/14/2020 to 4/14/2021, 1027 patients presented for screening mammography and met study inclusion criteria. Patients with history of baseline lymphadenopathy or prior cancer diagnosis were excluded. RESULTS: Of the 1027 women, 43 were recalled for unilateral sLAD. 34 women received a COVID-19 vaccination ipsilateral to the sLAD (Pfizer n=19, 44.2%; Moderna n=15, 34.9%), 9 did not (20.9%). Incidence of unilateral axillary sLAD was significantly higher (p-value<0.01) in those who received a COVID-19 vaccination within approximately 7 weeks preceding screening mammogram. 13.2% of patients who received the Pfizer vaccine and 9.5% of patients who received the Moderna vaccine developed sLAD. Moderna's vaccine elicited a more robust reaction in the elderly (Moderna 63.7 years vs. Pfizer 59.7 years). For both vaccines, sLAD resolved on average 46.5 days after the last COVID-19 vaccine (p=0.44). CONCLUSION: Women who have received either mRNA COVID-19 vaccines may benefit from scheduling their screening mammogram before vaccination or consider delaying screening mammography 8 weeks. While Pfizer may have an overall more robust immune response, Moderna may elicit a stronger immune response in elderly women. SUMMARY: Women who received a COVID-19 vaccination before screening mammography were significantly more likely to present with subclinical axillary lymphadenopathy than women who did not receive the vaccine. KEY RESULTS: 13.2% of women who received a Pfizer-BioNTech vaccine exhibited subclinical axillary lymphadenopathy compared to 9.5% of those who received the Moderna vaccine. Only 1.2 % of those who did not receive a vaccine presented with subclinical unilateral axillary lymphadenopathy. The average time of resolution of the lymphadenopathy on diagnostic mammogram was 46.5 days overall, with Pfizer-BioNTech taking 50.7 days and Moderna 41.5 days.

Sagoo, N.S., Haider, A.S., Ozair, A., Vannabouathong, C., Rahman, M., Haider, M., Sharma, N., Raj, K.M., Raj, S.D., Paul, J.C., Steinmetz, M.P., Adogwa, O., Aoun, S.G., Passias, P.G. and Vira, S. (2021). “Percutaneous image-guided cryoablation of spinal metastases: A systematic review.” J Clin Neurosci.

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Percutaneous cryoablation (PCA) is a minimally invasive technique that has been recently used to treat spinal metastases with a paucity of data currently available in the literature. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Prospective or retrospective studies concerning metastatic spinal neoplasms treated with current generation PCA systems and with available data on safety and clinical outcomes were included. In the 8 included studies (7 retrospective, 1 prospective), a total of 148 patients (females = 63%) underwent spinal PCA. Tumors were located in the cervical (3/109 [2.8%], thoracic (74/109 [68.8%], lumbar (37/109 [33.9%], and sacrococcygeal (17/109 [15.6%] regions. Overall, 187 metastatic spinal lesions were treated. Thermo-protective measures (e.g., carbo-/hydro-dissection, thermocouples) were used in 115/187 [61.5%] procedures. For metastatic spinal tumors, the pooled mean difference (MD) in pain scores from baseline on the 0-10 numeric rating scale was 5.03 (95% confidence interval [CI]: 4.24 to 5.82) at a 1-month follow-up and 4.61 (95% CI: 3.27 to 5.95) at the last reported follow-up (range 24-40 weeks in 3/4 studies). Local tumor control rates ranged widely from 60% to 100% at varying follow-ups. Grade I-II complications were reported in 9/148 [6.1%] patients and grade III-V complications were reported in 3/148 [2.0%]) patients. PCA, as a stand-alone or adjunct modality, may be a viable therapy in appropriately selected patients with painful spinal metastases who were traditionally managed with open surgery and/or radiation therapy.

Rahimi, R.S., Safadi, R., Thabut, D., Bhamidimarri, K.R., Pyrsopoulos, N., Potthoff, A., Bukofzer, S. and Bajaj, J.S. (2021). “Efficacy and Safety of Ornithine Phenylacetate for Treating Overt Hepatic Encephalopathy in a Randomized Trial.” Clin Gastroenterol Hepatol 19(12): 2626-2635.e2627.

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BACKGROUND & AIMS: Hepatic encephalopathy (HE) is associated with increased morbidity, mortality, and health care resource use. In this phase 2b study, we evaluated the efficacy and safety of ornithine phenylacetate (OP), an ammonia scavenger, in hospitalized patients with cirrhosis, increased levels of ammonia at screening, and acute or overt HE. METHODS: We conducted a double-blind study of 231 patients with cirrhosis and HE at multiple sites in North America, Europe, Israel, and Australia from January 7, 2014, through December 29, 2016. Patients were assigned randomly to groups that received placebo or OP (10, 15, or 20 g/d, based on the severity of liver disease), plus each institution’s standard of care (eg, lactulose to achieve 2-3 bowel movements with or without rifaximin, in accordance with guidelines). The primary end point was time to confirmed clinical response, defined as reduction to HE staging tool (HEST) stage 2 from baseline HEST stages 3/4 or improvement to HEST stages 0/1 from baseline stage 2, in the intent-to-treat population (all patients with increased levels of ammonia at screening, determined by a local laboratory). RESULTS: Median times to clinical improvement, based on ammonia measurements at local laboratories, did not differ significantly between the groups given OP vs the placebo group (P = .129). Analyses of central laboratory-confirmed increases in levels of ammonia at baseline (n = 201) showed clinical improvement in HE at a median of 21 hours sooner in groups given OP vs placebo. The percentages of patients with any specific adverse event did not differ significantly between groups. Serious adverse events occurred in 25% of patients in the OP group and in 29% in the placebo group (P = .552). CONCLUSIONS: In a randomized controlled trial of patients with cirrhosis and HE, we found no significant difference in time to clinical improvement between patients given OP vs placebo. However, OP appears to be safe and should undergo further testing for treatment of hyperammonemia in hospitalized patients receiving treatment for the underlying precipitant of acute or overt HE. ClinicalTrials.gov no: NCT01966419.

Lai, J.C., Shui, A.M., Duarte-Rojo, A., Ganger, D.R., Rahimi, R.S., Huang, C.Y., Yao, F., Kappus, M., Boyarsky, B., McAdams-Demarco, M., Volk, M.L., Dunn, M.A., Ladner, D.P., Segev, D.L., Verna, E.C. and Feng, S. (2021). “Frailty, Mortality, and Healthcare Utilization after Liver Transplantation: From the Multi-Center Functional Assessment in Liver Transplantation (FrAILT) Study.” Hepatology Dec 4. [Epub ahead of print].

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BACKGROUND: Frailty is a well-established risk factor for poor outcomes in patients with cirrhosis awaiting liver transplantation (LT), but whether it predicts outcomes among those who have undergone LT is unknown. METHODS: Adults LT recipients from 8 U.S. centers (2012-2019) were included. Pre-LT frailty was assessed in the ambulatory clinic using the Liver Frailty Index (LFI). “Frail” was defined by an optimal cut point of LFI≥4.5. We used the 75%ile to define “prolonged” post-LT length of stay (LOS; ≥12d), intensive care unit (ICU; ≥4d) days, and inpatient days within 90 post-LT days (≥17d). RESULTS: Of 1,166 LT recipients, 21% were frail pre-LT. Cumulative incidence of death at 1- and 5-years was 6% and 16% for frail and 4% and 10% for non-frail patients (overall logrank p=0.02). Pre-LT frailty was associated with an unadjusted 62% increased risk of post-LT mortality (95% CI 1.08-2.44); after adjustment for body mass index, HCC, donor age, and DCD status, the HR was 2.13 (95% CI 1.39-3.26). Patients who were frail versus non-frail experienced a higher adjusted odds of prolonged LT LOS [odds ratio (OR) 2.00, 95% CI 1.47-2.73], ICU stay (OR 1.56, 95% CI 1.12-2.14), inpatient days within 90 post-LT days (OR 1.72, 95% 1.25-2.37), and non-home discharge (OR 2.50, 95% 1.58-3.97). CONCLUSIONS: Compared to non-frail patients, frail LT recipients had a higher risk of post-LT death and greater post-LT healthcare utilization, although overall post-LT survival was acceptable. These data lay the foundation to investigate whether targeting pre-LT frailty will improve post-LT outcomes and reduce resource utilization.

Terrault, N.A., Wahed, A.S., Feld, J.J., Cooper, S.L., Ghany, M.G., Lisker-Melman, M., Perrillo, R., Sterling, R.K., Khalili, M., Chung, R.T., Rosenthal, P., Fontana, R.J., Sarowar, A., Lau, D., Wang, J., Lok, A.S. and Janssen, H. (2021). “Incidence and Prediction of HBsAg Seroconversion in a Prospective Multi-ethnic HBeAg-Negative Chronic Hepatitis B Cohort.” Hepatology Nov 7. [Epub ahead of print].

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BACKGROUND & AIMS: Achieving HBsAg loss is an important landmark in the natural history of chronic hepatitis B. A more personalized approach to prediction of HBsAg loss is relevant in couseling patients. This study sought to develop and validate a prediction model for HBsAg loss based on quantitative HBsAg levels and other baseline characteristics. METHODS: Hepatitis B Research Network (HBRN) is a prospective cohort including 1240 untreated HBeAg-negative patients (1150 adults, 90 children) with median follow-up of 5.5 years. Incidence rates of HBsAg loss and anti-HBs acquisition were determined and a predictor score of HBsAg loss using readily available variables was developed and externally validated. RESULTS: Crude incidence rates of HBsAg loss and anti-HBs acquisition were 1.6 and 1.1 per 100 person-years (PY); 67 achieved sustained HBsAg loss for an incidence rate of 1.2 per 100 PY. Increased HBsAg loss was significantly associated with older age, non-Asian race, HBV phenotype (inactive carrier vs others), HBV genotype A, lower HBV DNA levels and lower and greater change in quantitative HBsAg (∆qHBsAg). The HBRN-SQuARe (sex,∆quantHBsAg, age, race) score predicted HBsAg loss over time with AUROC (95% confidence intervals) at 1 and 3 years of 0.99 (95% CI: 0.987-1.00) and 0.95 (95% CI 0.91-1.00), respectively. Validation in another cohort of 1253 HBeAg-negative patients with median follow-up of 3.1 years, HBRN-SQuARe predicted HBsAg loss at 1 and 3 years with AUROC values of 0.99 [0.98-1.00] and 0.88 [0.77-0.99], respectively. CONCLUSION: HBsAg loss in predominantly untreated patients with HBeAg-negative chronic hepatitis B can be accurately predicted over a 3-year horizon using a simple validated score (HBRN-SQuARe). This prognostication tool can be used to support patient care and counseling.