The Diagnostic Value of PSMA PET-CT in Differentiating Medication-Related Osteonecrosis of the Jaw and Metastasis to the Jawbone.

INTRODUCTION: Medication-related osteonecrosis of the jaw (MRONJ) and jaw metastasis might share similar clinical and radiographic characteristics, with both demonstrating FDG uptake on PET-CT. Prostate-specific membrane antigen (PSMA) PET-CT is used to demonstrate prostate cancer dissemination. Unlike FDG PET-CT, PSMA PET-CT is more specific to cancer than to inflammation. Therefore, we hypothesized that it might be a useful tool to differentiate between MRONJ and jaw metastasis. MATERIALS AND METHODS: All files of prostate cancer patients diagnosed with MRONJ and with available PSMA PET-CT studies were retrieved. A similar number of solid cancer patients with MRONJ and with available FDG PET-CT studies served as a second study group. All studies were reviewed by two blinded co-investigators (LD, MF). RESULTS: Seventeen patients who underwent PSMA PET-CT (24 studies) and 15 patients who underwent FDG PET-CT (29 studies) met the inclusion criteria. All patients with FDG PET-CT studies showed pathological uptake at the site of MRONJ in at least one of their studies versus only 23.5% of patients in the PSMA PET-CT group (P < 0.001). FDG PET-CT studies showed pathological uptake in 89.6% of the studies compared to only 20.8% in the PSMA PET-CT group (P < 0.001). The mean standardized uptake value (SUVmax) and the mean uptake volume in the FDG PET-CT group were significantly higher compared to the PSMA PET-CT group (P < 0.001 and P < 0.005, respectively). The interclass correlation coefficient for all parameters was higher than 0.95. CONCLUSIONS: PSMA PET-CT is useful to differentiate between MRONJ and jaw metastasis.

Salt-inducible kinase induces cytoplasmic histone deacetylase 4 to promote vascular calcification.

A pathologic osteochondrogenic differentiation of vascular smooth muscle cells (VSMCs) promotes arterial calcifications, a process associated with significant morbidity and mortality. The molecular pathways promoting this pathology are not completely understood. We studied VSMCs, mouse aortic rings, and human aortic valves and showed here that histone deacetylase 4 (HDAC4) is upregulated early in the calcification process. Gain- and loss-of-function assays demonstrate that HDAC4 is a positive regulator driving this pathology. HDAC4 can shuttle between the nucleus and cytoplasm, but in VSMCs, the cytoplasmic rather than the nuclear activity of HDAC4 promotes calcification, and a nuclear-localized mutant of HDAC4 fails to promote calcification. The cytoplasmic location and function of HDAC4 is controlled by the activity of salt-inducible kinase (SIK). Pharmacologic inhibition of SIK sends HDAC4 to the nucleus and inhibits the calcification process in VSMCs, aortic rings, and in vivo In the cytoplasm, HDAC4 binds and its activity depends on the adaptor protein ENIGMA (Pdlim7) to promote vascular calcification. These results establish a cytoplasmic role for HDAC4 and identify HDAC4, SIK, and ENIGMA as mediators of vascular calcification.

[Women pioneers: first female cardiothoracic surgeons in the USA and in Israel].

At the beginning of the 1960's, three female doctors managed to break the glass ceiling and become the first female cardiothoracic surgeons in the USA. Since then, the number of certified female cardiothoracic surgeons has steadily increased. Nevertheless, females stilt only account for a minority of cardiothoracic surgeons in the USA. In Israel, three women have become specialists in cardiothoracic surgery over the last two decades, aLthough these surgeons are working as general thoracic surgery consultants, without any representative females in cardiac surgery.

Early and late outcomes of single versus bilateral internal thoracic artery revascularization for patients in critical condition.

OBJECTIVE: The optimal surgical approach for critically ill patients with complex coronary disease remains uncertain. We compared outcomes of bilateral internal thoracic artery (BITA) versus single ITA (SITA) revascularization in critical patients. METHODS: We evaluated 394 consecutive critical patients with multi-vessel disease who underwent CABG during 1996-2001. Outcomes measured were early mortality, strokes, myocardial-infarctions, sternal infections, revisions for bleeding, and late survival. The critical preoperative state was acknowledged concisely by one or more of the following: preoperative ventricular tachycardia/fibrillation, aborted sudden cardiac death, or the need for mechanical ventilation or for preoperative insertion of intra-aortic-balloon counter-pulsation. RESULTS: During the study period, 193 of our patients who underwent SITA and 201 who underwent BITA were in critical condition. The SITA group was older (mean 68.0 vs. 63.3 years, p = 0.001) and higher proportions were females (28.5% vs. 18.9% p = 0.025), after recent-MI (69.9% vs. 57.2% p = 0.009) and with left-main disease (38.3% vs. 49.3% p = .029); the median logistic EuroSCORE was higher (0.2898 vs. 0.1597, p<0.001). No statistically significant differences were observed between the SITA and BITA groups in 30-day mortality; and in rates of early CVA, MI and sternal infections (13.0% vs. 8.5%, p = 0.148; 4.1% vs. 6.0%, p = 0.49; 6.7% vs. 4.5%, p = 0.32 and 2.1% vs. 2.5%, p>0.99, respectively). Long-term survival (median follow-up of 15 years, interquartile-range: 13.57-15) was better in the BITA group (median 14.39 vs. 9.31± 0.9 years, p = 0.001). Propensity-score matching (132 matched pairs) also yielded similar early outcomes and improved long-term survival (median follow-up of 15 years, interquartile-range: 13.56-15) for the BITA group (median 12.49±1.71 vs. 7.63±0.99 years, p = 0.002). In multivariable analysis, BITA revascularization was found to be a predictor for improved survival (hazard-ratio of 0.419, 95%CI 0.23-0.76, p = 0.004). CONCLUSIONS: This study demonstrated long-term survival benefit for BITA revascularization in patients in a critical pre-operative state who presented for surgical revascularization.