Research Spotlight

Cimino, S., Agati, L., Filomena, D., Maestrini, V., Monosilio, S., Birtolo, L. I., Mocci, M., Mancone, M., Sardella, G., Grayburn, P. and Fedele, F. (2022). “3D Echo Characterization of Proportionate and Disproportionate Functional Mitral Regurgitation before and after Percutaneous Mitral Valve Repair.” J Clin Med 11(3).

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BACKGROUND: The impact of percutaneous mitral valve repair (PMVr) on long-term prognosis in patients with functional mitral regurgitation (FMR) is still unclear. Recently, a new conceptual framework classifying FMR as proportionate (P-MR) and disproportionate (D-MR) was proposed, according to the effective regurgitant orifice area/left ventricular end-diastolic volume (EROA/LVEDV) ratio. The aim was to assess its possible influence on PMVr efficacy. METHODS: A total of 56 patients were enrolled. MV annulus, LV volumes and function were assessed. Global longitudinal strain (GLS) was also calculated. Patients were divided into two groups, according to the EROA/LVEDV ratio. Echocardiographic follow-up was performed after 6 months, and adverse events were collected after 12 months. RESULTS: D-MR patients (n = 28, 50%) had a significantly more elliptical MV annulus (p = 0.048), lower tenting volume (p = 0.01), higher LV ejection fraction (LVEF: 32 ± 7 vs. 26 ± 5%, p = 0.003), lower LVEDV, LV end-systolic volume (LVESV) and mass (LVEDV/i: 80 ± 20 vs. 126 ± 27 mL, p = 0.001; LVESV/i: 60 ± 20 vs. 94 ± 23 mL, p < 0.001; LV mass: 249 ± 63 vs. 301 ± 69 gr, p = 0.035). GLS was more impaired in P-MR (p = 0.048). After 6 months, P-MR patients showed a higher rate of MR recurrence. After 12 months, the rate of CV death and rehospitalization due to HF was significantly higher in P-MR patients (46% vs. 7%, p < 0.001). P-MR status was strongly associated with CV death/rehospitalization (HR = 3.4, CI 95% = 1.3-8.6, p = 0.009). CONCLUSIONS: Patients with P-MR seem to have worse outcomes after PVMr than D-MR patients. Our study confirms the importance of the EROA/LVEDV ratio in defining different subsets of FMR based on the anatomical characteristic of MV and LV.

Tenforde, M. W., Patel, M. M., Gaglani, M., Ginde, A. A., Douin, D. J., Talbot, H. K., Casey, J. D., Mohr, N. M., Zepeski, A., McNeal, T., Ghamande, S., Gibbs, K. W., Files, D. C., Hager, D. N., Shehu, A., Prekker, M. E., Erickson, H. L., Gong, M. N., Mohamed, A., Johnson, N. J., Srinivasan, V., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Monto, A. S., Khan, A., Hough, C. L., Busse, L. W., Duggal, A., Wilson, J. G., Qadir, N., Chang, S. Y., Mallow, C., Rivas, C., Babcock, H. M., Kwon, J. H., Exline, M. C., Botros, M., Lauring, A. S., Shapiro, N. I., Halasa, N., Chappell, J. D., Grijalva, C. G., Rice, T. W., Jones, I. D., Stubblefield, W. B., Baughman, A., Womack, K. N., Rhoads, J. P., Lindsell, C. J., Hart, K. W., Zhu, Y., Naioti, E. A., Adams, K., Lewis, N. M., Surie, D., McMorrow, M. L. and Self, W. H. (2022). “Effectiveness of a Third Dose of Pfizer-BioNTech and Moderna Vaccines in Preventing COVID-19 Hospitalization Among Immunocompetent and Immunocompromised Adults – United States, August-December 2021.” MMWR Morb Mortal Wkly Rep 71(4): 118-124.

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COVID-19 mRNA vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) provide protection against infection with SARS-CoV-2, the virus that causes COVID-19, and are highly effective against COVID-19-associated hospitalization among eligible persons who receive 2 doses (1,2). However, vaccine effectiveness (VE) among persons with immunocompromising conditions* is lower than that among immunocompetent persons (2), and VE declines after several months among all persons (3). On August 12, 2021, the Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for a third mRNA vaccine dose as part of a primary series ≥28 days after dose 2 for persons aged ≥12 years with immunocompromising conditions, and, on November 19, 2021, as a booster dose for all adults aged ≥18 years at least 6 months after dose 2, changed to ≥5 months after dose 2 on January 3, 2022 (4,5,6). Among 2,952 adults (including 1,385 COVID-19 case-patients and 1,567 COVID-19-negative controls) hospitalized at 21 U.S. hospitals during August 19-December 15, 2021, effectiveness of mRNA vaccines against COVID-19-associated hospitalization was compared between adults eligible for but who had not received a third vaccine dose (1,251) and vaccine-eligible adults who received a third dose ≥7 days before illness onset (312). Among 1,875 adults without immunocompromising conditions (including 1,065 [57%] unvaccinated, 679 [36%] 2-dose recipients, and 131 [7%] 3-dose [booster] recipients), VE against COVID-19 hospitalization was higher among those who received a booster dose (97%; 95% CI = 95%-99%) compared with that among 2-dose recipients (82%; 95% CI = 77%-86%) (p <0.001). Among 1,077 adults with immunocompromising conditions (including 324 [30%] unvaccinated, 572 [53%] 2-dose recipients, and 181 [17%] 3-dose recipients), VE was higher among those who received a third dose to complete a primary series (88%; 95% CI = 81%-93%) compared with 2-dose recipients (69%; 95% CI = 57%-78%) (p <0.001). Administration of a third COVID-19 mRNA vaccine dose as part of a primary series among immunocompromised adults, or as a booster dose among immunocompetent adults, provides improved protection against COVID-19-associated hospitalization.

Tenforde, M. W., Campbell, A. P., Michaels, M. G., Harrison, C. J., Klein, E. J., Englund, J. A., Selvarangan, R., Halasa, N. B., Stewart, L. S., Weinberg, G. A., Williams, J. V., Szilagyi, P. G., Staat, M. A., Boom, J. A., Sahni, L. C., Singer, M. N., Azimi, P. H., Zimmerman, R. K., McNeal, M. M., Talbot, H. K., Monto, A. S., Martin, E. T., Gaglani, M., Silveira, F. P., Middleton, D. B., Ferdinands, J. M. and Rolfes, M. A. (2022). “Clinical Influenza Testing Practices in Hospitalized Children at United States Medical Centers, 2015-2018.” J Pediatric Infect Dis Soc 11(1): 5-8.

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At nine US hospitals that enrolled children hospitalized with acute respiratory illness (ARI) during 2015-2016 through 2017-2018 influenza seasons, 50% of children with ARI received clinician-initiated testing for influenza and 35% of cases went undiagnosed due to lack of clinician-initiated testing. Marked heterogeneity in testing practice was observed across sites.

Naleway, A. L., Grant, L., Caban-Martinez, A. J., Wesley, M. G., Burgess, J. L., Groover, K., Gaglani, M., Yoon, S. K., Tyner, H. L., Meece, J., Kuntz, J. L., Yoo, Y. M., Schaefer-Solle, N., Olsho, L. E. W., Gerald, J. K., Rose, S., Thiese, M. S., Lundgren, J., Groom, H. C., Mak, J., Louzado Feliciano, P., Edwards, L. J., Lutrick, K., Dunnigan, K., Phillips, A. L., Lamberte, J. M., Noriega, R., Sokol, B. E., Odean, M., Ellingson, K. D., Smith, M., Hegmann, K. T., Respet, K., Dickerson, M., Cruz, A., Fleary, D. E., Murthy, K., Hunt, A., Azziz-Baumgartner, E., Gallimore-Wilson, D., Harder, J. A., Odame-Bamfo, L., Viergutz, J., Arvay, M., Jones, J. M., Mistry, P., Thompson, M. G. and Fowlkes, A. L. (2022). “Incidence of SARS-CoV-2 infection among COVID-19 vaccinated and unvaccinated healthcare personnel, first responders, and other essential and frontline workers: Eight US locations, January-September 2021.” Influenza Other Respir Viruses.

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BACKGROUND: We sought to evaluate the impact of changes in estimates of COVID-19 vaccine effectiveness on the incidence of laboratory-confirmed infection among frontline workers at high risk for SARS-CoV-2. METHODS: We analyzed data from a prospective frontline worker cohort to estimate the incidence of COVID-19 by month as well as the association of COVID-19 vaccination, occupation, demographics, physical distancing, and mask use with infection risk. Participants completed baseline and quarterly surveys, and each week self-collected mid-turbinate nasal swabs and reported symptoms. RESULTS: Among 1018 unvaccinated and 3531 fully vaccinated workers, the monthly incidence of laboratory-confirmed SARS-CoV-2 infection in January 2021 was 13.9 (95% confidence interval [CI]: 10.4-17.4), declining to 0.5 (95% CI -0.4-1.4) per 1000 person-weeks in June. By September 2021, when the Delta variant predominated, incidence had once again risen to 13.6 (95% CI 7.8-19.4) per 1000 person-weeks. In contrast, there was no reportable incidence among fully vaccinated participants at the end of January 2021, and incidence remained low until September 2021 when it rose modestly to 4.1 (95% CI 1.9-3.8) per 1000. Below average facemask use was associated with a higher risk of infection for unvaccinated participants during exposure to persons who may have COVID-19 and vaccinated participants during hours in the community. CONCLUSIONS: COVID-19 vaccination was significantly associated with a lower risk of SARS-CoV-2 infection despite Delta variant predominance. Our data demonstrate the added protective benefit of facemask use among both unvaccinated and vaccinated frontline workers.

Farberg, A. S., Fitzgerald, A. L., Ibrahim, S. F., Tolkachjov, S. N., Soleymani, T., Douglas, L. M., Kurley, S. J. and Arron, S. T. (2022). “Current Methods and Caveats to Risk Factor Assessment in Cutaneous Squamous Cell Carcinoma (cSCC): A Narrative Review.” Dermatol Ther (Heidelb) 12(2): 267-284.

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Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer, and the number of deaths due to cSCC is estimated to be greater than the number attributed to melanoma. While the majority of cSCC tumors are resectable with clear margins by standard excision practices, some lesions exhibit high-risk factors for which there is evidence of their association with recurrence, metastasis, and disease-specific death. The most commonly used staging systems and guidelines in the USA for cSCC are based on these clinical and pathologic high-risk factors; however, these are limited in their ability to predict adverse events, thus posing a challenge for implementing risk-directed patient management. Since the development of local recurrence and/or metastasis has a profound impact on the survival of patients with cSCC, accurate identification of patients at high risk for poor outcomes is critical, potentially allowing for early and appropriate adjuvant therapy. This review summarizes the current cSCC literature with a focus on how differing clinical assessments within each of the five selected risk factors (perineural invasion, differentiation, depth of invasion, size, and location) can influence the evaluation of patient outcomes, along with summarizing the utility of staging and guidelines, and highlighting the potential for molecular tools to improve upon cSCC risk assessment.