Citations

Background: Little guidance exists on effective management of postoperative atrial fibrillation (POAF) following noncardiac, nonthoracic (NCNT) surgery. Objectives: The purpose of this study was to identify whether a difference exists between intravenous (IV) metoprolol and diltiazem when used to achieve hemodynamically stable rate control in POAF following NCNT surgery. Methods: This retrospective cohort study examined critically ill adult surgical patients experiencing POAF with rapid ventricular response. Inclusion in the metoprolol or diltiazem treatment group was determined by the initial rate control agent chosen by the prescriber. The primary end point was hemodynamically stable rate control, defined by heart rate (HR) <110 beats/min and blood pressure >90 mm Hg, maintained for 6 hours. Main Results: Patients on metoprolol (n = 66) and diltiazem (n = 55) were similar in age, comorbidities, surgical procedure distribution, acuity of illness, and home rate and rhythm control medications continued during hospitalization; 76% of diltiazem-treated patients achieved hemodynamically stable rate control, compared with only 53% of those receiving metoprolol ( P = .005). Safety end points were similar between groups, including the portion requiring a new vasopressor or fluid bolus for hemodynamic support. Conclusions: In NCNT surgery, patients with POAF, IV diltiazem more effectively controlled HR and hemodynamics compared with metoprolol. Results warrant further research into optimal medical management of POAF in this population using these 2 agents.

Aims To explore the immunohistochemical utility of proliferating cell nuclear antigen (PCNA), insulin-like growth factor 2 (IGF2) and clusterin in the distinction between malignant and benign liver nodular lesions. Methods Immunohistochemical stains for PCNA, IGF2 and clusterin were performed on 284 liver nodular lesions, including 33 hepatocellular adenomas (HCA), 40 focal nodular hyperplasias (FNH), 77 large regenerative nodules (LRN) and 134 hepatocellular carcinomas (HCC). Results Strong and diffuse nuclear PCNA immunoreactivity was observed in 103 (77%) HCCs but in only 2 (6%) HCAs. None of the FNH and LRN cases showed a strong and diffuse staining pattern. All HCAs, 95% of FNHs and 92% of LRNs showed cytoplasmic IGF2 expression, with a strong staining observed in 70% of HCAs, 20% of FNHs and 30% of LRNs. This was in marked contrast to that observed in HCCs, where 66% of HCCs demonstrated a weak and focal/patchy immunostaining pattern and another 25% showed no detectable IGF2 immunoreactivity. In comparison with their adjacent non-lesional hepatocytes, 75% of HCCs showed decreased IGF2 expression. However, decreased IGF2 expression was not evident in HCAs, FNHs and LRNs. Cytoplasmic staining for clusterin was seen in both benign and malignant nodular lesions. However, an enhanced and exaggerated pericanalicular staining pattern was observed in 75% of HCCs, which was not demonstrated in HCAs, FNHs and LRNs. Conclusions PCNA, IGF2 and clusterin show unique immunostaining characteristics in HCCs, which can be useful adjuncts to other currently available markers to aid in the distinction of HCC from benign liver nodular lesions.

Zebrafish Na+/H+exchanger 3b (zNHE3b) is highly expressed in the apical membrane of ionocytes where Na+is absorbed from ion-poor fresh water against a concentration gradient. Much in vivo data indicated that zNHE3b is involved in Na+absorption but not leakage. However, zNHE3b-mediated Na+absorption has not been thermodynamically explained, and zNHE3b activity has not been measured. To address this issue, we overexpressed zNHE3b in Xenopus oocytes and characterized its activity by electrophysiology. Exposure of zNHE3b oocytes to Na+-free media resulted in significant decrease in intracellular pH (pHi) and intracellular Na+activity ( aNai). aNaiincreased significantly when the cytoplasm was acidified by media containing CO2-HCO3−or butyrate. Activity of zNHE3b was inhibited by amiloride or 5-ethylisopropyl amiloride (EIPA). Although the activity was accompanied by a large hyperpolarization of ∼50 mV, voltage-clamp experiments showed that Na+/H+exchange activity of zNHE3b is electroneutral. Exposure of zNHE3b oocytes to medium containing NH3/NH4+resulted in significant decreases in pHiand aNaiand significant increase in intracellular NH4+activity, indicating that zNHE3b mediates the Na+/NH4+exchange. In low-Na+(0.5 mM) media, zNHE3b oocytes maintained aNaiof 1.3 mM, and Na+-influx was observed when pHiwas decreased by media containing CO2-HCO3−or butyrate. These results provide thermodynamic evidence that zNHE3b mediates Na+absorption from ion-poor fresh water by its Na+/H+and Na+/NH4+exchange activities.