Research Spotlight

Minzenmayer, A.N., Taylor, K., Housewright, C.D., Bicknell, L.M., Hendrick, S.J., Tsai, J.H. and Siref, A. (2021). “Indolent CD8+ primary cutaneous T-cell lymphoma involving the eyelid of an adolescent.” J Cutan Pathol Jul 4. [Epub ahead of print].

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Primary cutaneous acral CD8+ T-cell lymphoma (PCACTL) is currently a provisional entity defined as a rare cutaneous proliferation of atypical CD8+ lymphocytes that preferentially involves acral sites and has a good prognosis. We present a case of primary cutaneous CD8+ T-cell lymphoma involving the eyelid of an adolescent male. The case shares features with PCACTL, including indolent clinical behavior and expression of CD68 in a Golgi-associated dot-like pattern; however, other features differ significantly from PCACTL as currently defined by the World Health Organization (WHO). These features include ulceration, expression of CD56, granzyme B, and perforin, and a high proliferative index. Given these discrepancies, our case is currently best classified as a CD8+ primary cutaneous peripheral T-cell lymphoma, not otherwise specified. We review the differential diagnosis for this case and suggest expanding the definition of PCACTL.

Hamandi, M., Squiers, J.J., Lanfear, A.T., Banwait, J.K., Meidan, T.G., Smith, R.L., Hutcheson, K., DiMaio, J.M., Mack, M.J., George, T.J. and Ryan, W.H. (2021). “Minimally invasive mitral valve surgery after previous sternotomy: A propensity-matched analysis.” J Card Surg Jun 6. [Epub ahead of print].

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BACKGROUND: Although the incidence of mitral valve (MV) surgery after previous open-heart surgery is increasing, there is no consensus regarding the optimal surgical approach. Reoperative MV surgery is most commonly performed via sternotomy (ST). We sought to determine whether minimally-invasive (MIS) reoperative MV surgery is safe and feasible. METHODS: All patients with a history of ST undergoing MV surgery with or without concomitant tricuspid or atrial fibrillation surgery at a single institution from 2007 to 2018 were retrospectively reviewed. ST and MIS approaches were compared using propensity-matched analysis. The coprimary endpoints were operative mortality and 1-year survival, and secondary endpoints were operative complications and length of stay. RESULTS: A total of 305 isolated MV reoperations were performed: 199 (65%) MIS and 106 (35%) ST. MIS patients were older than ST patients (71 [63, 76.5] vs. 66 [56, 72] years, p < .01), more likely to have undergone prior coronary artery bypass grafting (57% vs. 27%, p < .01), and less likely to have had prior valve surgery (55% vs. 78%, p < .01). In unmatched comparisons, operative mortality was significantly lower among MIS patients (3.0% vs. 8.5%, p = .04), but 1-year mortality was similar (14.4% vs. 15.6%, p = .8). After propensity matching, 88 pairs had excellent balance across baseline characteristics. Mortality was similar among MIS and ST patients at 30 days (3.4% vs. 8%, p = .19) and 1 year (15.9% vs. 16.5%, p = .9). RBC and fresh frozen plasma transfusions were significantly lower in the MIS group (p < .01). CONCLUSIONS: A minimally invasive approach is a safe alternative in patients with prior ST undergoing MV surgery.

Hahn, R.T., Douglas, P.S., Jaber, W.A., Leipsic, J., Kapadia, S., Thourani, V.H., Makkar, R., Kodali, S., Clavel, M.A., Khalique, O.K., Weissman, N.J., Blanke, P., Chen, Y., Smith, C.R., Mack, M.J., Leon, M.B. and Pibarot, P. (2021). “Doppler Velocity Index Outcomes Following Surgical or Transcatheter Aortic Valve Replacement in the PARTNER Trials.” JACC Cardiovasc Interv Jun 23;S1936-8798(21)00682-8. [Epub ahead of print].

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OBJECTIVES: The aim of this study was to assess the association between Doppler velocity index (DVI) and 2-year outcomes for balloon-expandable SAPIEN 3 transcatheter aortic valve replacement (TAVR) and for surgical aortic valve replacement (SAVR). BACKGROUND: DVI >0.35 is normal for a prosthetic valve, but recent studies suggest that DVI <0.50 is associated with poor outcomes following TAVR. METHODS: Patients with severe aortic stenosis enrolled in the PARTNER (Placement of Aortic Transcatheter Valve) 2 (intermediate surgical risk) or PARTNER 3 (low surgical risk) trial undergoing TAVR (n = 1,450) or SAVR (n = 1,303) were included. Patients were divided into 3 DVI groups on the basis of core laboratory-assessed discharge or 30-day echocardiograms: DVI(LOW) (≤0.35), DVI(INTERMEDIATE) (>0.35 to ≤0.50), and DVI(HIGH) (>0.50). Two-year outcomes were assessed. RESULTS: Following TAVR, there were no differences among the 3 DVI groups in composite outcomes of death, stroke, or rehospitalization or in any individual components of 2-year outcomes (P > 0.70 for all). Following SAVR, there was no difference among DVI groups in the composite outcome (P = 0.27), but there was a significant association with rehospitalization (P = 0.02). Restricted cubic-spline analysis for combined outcomes showed an increased risk with post-SAVR DVI ≤0.35 but no relationship post-TAVR. DVI ≤0.35 was associated with increased 2-year composite outcome for SAVR (HR: 1.81; 95% CI: 1.29-2.54; P < 0.001), with no adverse outcomes for TAVR (P = 0.86). CONCLUSIONS: In intermediate- and low-risk cohorts of the PARTNER trials, DVI ≤0.35 predicted worse 2-year outcomes following SAVR, driven primarily by rehospitalization, with no adverse outcomes associated with DVI following TAVR with the balloon-expandable SAPIEN 3 valve.

Ghergurovich, J.M., Lang, J.D., Levin, M.K., Briones, N., Facista, S.J., Mueller, C., Cowan, A.J., McBride, M.J., Rodriguez, E.S.R., Killian, A., Dao, T., Lamont, J., Barron, A., Su, X., Hendricks, W.P.D., Espina, V., Von Hoff, D.D., O’Shaughnessy, J. and Rabinowitz, J.D. (2021). “Local production of lactate, ribose phosphate, and amino acids within human triple-negative breast cancer.” Med (N Y) 2(6): 736-754.

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BACKGROUND: Upregulated glucose metabolism is a common feature of tumors. Glucose can be broken down by either glycolysis or the oxidative pentose phosphate pathway (oxPPP). The relative usage within tumors of these catabolic pathways remains unclear. Similarly, the extent to which tumors make biomass precursors from glucose, versus take them up from the circulation, is incompletely defined. METHODS: We explore human triple negative breast cancer (TNBC) metabolism by isotope tracing with [1,2-(13)C]glucose, a tracer that differentiates glycolytic versus oxPPP catabolism and reveals glucose-driven anabolism. Patients enrolled in clinical trial NCT03457779 and received IV infusion of [1,2-(13)C]glucose during core biopsy of their primary TNBC. Tumor samples were analyzed for metabolite labeling by liquid chromatography-mass spectrometry (LC-MS). Genomic and proteomic analyses were performed and related to observed metabolic fluxes. FINDINGS: TNBC ferments glucose to lactate, with glycolysis dominant over the oxPPP. Most ribose phosphate is nevertheless produced by oxPPP. Glucose also feeds amino acid synthesis, including of serine, glycine, aspartate, glutamate, proline and glutamine (but not asparagine). Downstream in glycolysis, tumor pyruvate and lactate labeling exceeds that found in serum, indicating that lactate exchange via monocarboxylic transporters is less prevalent in human TNBC compared with most normal tissues or non-small cell lung cancer. CONCLUSIONS: Glucose directly feeds ribose phosphate, amino acid synthesis, lactate, and the TCA cycle locally within human breast tumors.

Genena, K.H., Ahmed, S., Szerlip, H.M. and Schwartz, J.C. (2021). “Half the V by 120: A practical approach to the prevention of the dialysis disequilibrium syndrome.” Hemodial Int June 18. [Epub ahead of print].

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The dialysis disequilibrium syndrome (DDS) results from osmotic shifts between the blood and the brain compartments. Patients at risk for DDS include those with very elevated blood urea nitrogen, concomitant hypernatremia, metabolic acidosis, and low total body water volumes. By understanding the underlying pathophysiology and applying urea kinetic modeling, it is possible to avoid the occurrence of this disorder. A urea reduction ratio (URR) of no more than 40%-45% over 2 h is recommended for the initial hemodialysis treatment. The relationship between the URR and Kt/V is useful when trying to model the dialysis treatment to a specific URR target. A simplified relationship between Kt/V and URR is provided by the equation: Kt/V = -ln (1 - URR). A URR of 40% is roughly equivalent to a Kt/V of 0.5. The required dialyzer urea clearance to achieve this goal URR in a 120-min treatment can simply be calculated by dividing half the patient’s volume of distribution of urea by 120. The blood flow rate and dialyzer mass transfer coefficient (K(0) A) required to achieve this clearance can then be plotted on a nomogram. Other methods to reduce the risk of DDS are reviewed, including the use of continuous renal replacement therapy.