Acute colonic pseudo-obstruction: a retrospective review of the surgical outcomes.

PURPOSE: Limited data exist regarding the surgical outcomes of acute colonic pseudo-obstruction (ACPO), commonly referred to as Ogilvie syndrome, in modern clinical practice. The prevailing belief is that surgery should be avoided due to previously reported high mortality rates. We aimed to describe the surgical results of ACPO treated within our institution. METHODS: Our prospectively maintained colorectal surgery registry was queried for patients diagnosed with ACPO, who underwent surgery between 2009 and 2022. Postoperative complications were graded according to Clavien-Dindo (CD) classification. The primary outcome was postoperative mortality. RESULTS: A total of 32 patients who underwent surgery for ACPO were identified. Overall, nonoperative therapy was initially administered to 21 patients (65.6%). The surgeries performed included total abdominal colectomy (15, 43.1%), ascending colectomy with end ileostomy (8, 25%), transverse colostomy (5, 15.6%), ileostomy and transverse colostomy (3, 9.4%), and Hartmann's operation (1, 3.1%). Severe postoperative complications (CD grade 3 or 4) occurred in five patients (15.6%). No recurrence of ACPO was observed and no patient required reoperation. The average postoperative length of stay was 14.5 days, 30-day mortality was 6.3% (n = 2), and 90-day mortality was 15.6% (n = 5) due to complications of underlying comorbidities. CONCLUSIONS: Surgical treatment was effective for patients with ACPO refractory to medical therapy or presenting with acute complications. Although postoperative complications were frequent, both the 30- and 90-day mortality rates were lower than previously documented in the literature. Further investigations are warranted to determine the optimal surgical strategy, which may involve total or segmental colectomy, or diversion alone without resection.

Pretreatment colostomy in patients with anal squamous cell carcinoma: Risk factors for a permanent stoma.

BACKGROUND: The current standard of care for anal squamous cell carcinoma (SCC) is concurrent chemoradiation (CRT), which enables tumor eradication while preserving the anal sphincter. Patients with locally advanced tumors, however, may experience complications that preclude treatment before stoma creation. OBJECTIVE: To evaluate the reversal rate of pretreatment stomas and the risk factors associated with nonreversal. METHODS: This single-institution retrospective cohort study using a prospective database included patients diagnosed with anal SCC from January 2008 to December 2020 who required a stoma before curative CRT. RESULTS: In total, 651 patients were identified; 65 required a stoma before chemoradiation due to obstruction (43.1%), rectovaginal fistula (20%), and perianal sepsis (36.9%). The stoma was reversed in nine patients after a mean follow-up of 35.8 months. Risk factors associated with a permanent stoma were perianal sepsis (p = 0.010), interruptions during radiotherapy for more than 7 days (p = 0.010), male sex (p = 0.013), poor performance status (Eastern Cooperative Oncology Group [ECOG] ≥ 2) (p = 0.023), large tumors (p = 0.045), and cisplatin-based chemotherapy (p = 0.047). CONCLUSIONS: Pretreatment stomas are unlikely to be reversed, and risk factors for a permanent stoma are perianal sepsis, interruptions during radiotherapy for more than 7 days, male sex, poor performance status (ECOG ≥ 2), large tumors, and cisplatin-based chemotherapy.

Selective late sodium current blockade with GS-458967 markedly reduces ischemia-induced atrial and ventricular repolarization alternans and ECG heterogeneity.

BACKGROUND: Ischemic heart disease is associated with dual risk for atrial and ventricular arrhythmias. OBJECTIVE: We examined whether selectively targeting late sodium channel current (INa) with GS-458967 (hereafter GS967) can reduce cardiac electrical instability and compared its effects to a clinically relevant dose of flecainide. METHODS: Electrode catheters were positioned on the left atrial appendage and left ventricle of anesthetized pigs to monitor repolarization alternans and electrocardiographic heterogeneity before and during left circumflex coronary artery stenosis (75% flow reduction) before and after GS967 (0.4 mg/kg, intravenously [IV]) or flecainide (1 mg/kg, IV, bolus over 2 minutes followed by 1 mg/(kg·h), IV, for 1 hour) administration. RESULTS: Left circumflex coronary artery stenosis increased atrial repolarization alternans by 520% (from 9.4 ± 1.2 to 58.3 ± 11.3 µV; P = .029) and T-wave alternans by 1038% (from 30.7 ± 8.2 to 349.3 ± 103.8 µV; P = .049). GS967 prevented ischemia-induced increases in alternans in the left atrium (19.3 ± 5.6 µV vs 58.3 ± 11.3 µV; P = .023) and left ventricle (217.9 ± 95.8 µV vs 349.3 ± 103.8 µV; P < .001) (n = 7). GS967 reduced ischemia-induced increases in depolarization heterogeneity (atrium: from 45% to 28%; ventricle: from 92% to 51%) and repolarization heterogeneity (atrium: 43% to 23%; ventricle: 137% to 91%). GS967 did not alter heart rate, arterial blood pressure, PR and QT intervals, or QRS duration, but it mildly decreased contractility (left ventricular dP/dt) during ischemia, which was consistent with late INa inhibition. Flecainide (n = 7) amplified ischemia-induced increase in atrial and ventricular repolarization alternans, electrocardiographic heterogeneity, and ventricular fibrillation incidence. CONCLUSION: Selective late INa inhibition with GS967 exerts potent protective effects against ischemia-induced depolarization and repolarization abnormalities in both atria and ventricles.

Inhibition of I(f) in the atrioventricular node as a mechanism for dronedarone's reduction in ventricular rate during atrial fibrillation.

BACKGROUND: In clinical trials, dronedarone lowers ventricular rate during atrial fibrillation (AF). This agent was recently demonstrated to inhibit If in the sinoatrial node. OBJECTIVE: The purpose of this study was to examine whether dronedarone inhibits If at the atrioventricular (AV) node to reduce ventricular rate during AF by slowing conduction at the AV node. METHODS: We studied the effects of dronedarone (1.0 mg/kg IV bolus) before and after administration of the If inhibitor ivabradine (0.5 mg/kg IV). Ventricular rate, mean arterial pressure, dominant frequency of AF, PR and QT intervals, and atrial (AERP) and ventricular effective refractory periods (VERP) were measured during atrial pacing at 150 bpm in an anesthetized pig model of AF induced by intrapericardial acetylcholine and burst pacing. RESULTS: Dronedarone reduced ventricular rate during AF by 22.1% (from 213 ± 11.1 bpm to 166 ± 8.3 bpm, P = .01) and increased PR interval by 8.7% (from 173 ± 5.6 ms to 188 ± 5.2 ms, P = .001), QT interval by 3.3% (from 272 ± 6.2 ms to 281 ± 4.9 ms, P = .05), and AERP and VERP by 6.2% and 11.7%, respectively. All other parameters remained unchanged. Dronedarone plasma levels were low (29 ± 4 nM), and concentration in tissue was 15- to 21-fold higher than in plasma. Ivabradine reduced ventricular rate during AF by 39.5% (from 200 ± 14.6 bpm to 121 ± 20.1 bpm, P = .005) and increased PR interval by 20.4% (from 157 ± 9.5 ms to 189 ± 7.4 ms, P <.05). Administration of dronedarone after ivabradine did not further alter these endpoints. CONCLUSION: Dronedarone, which is concentrated in myocardial tissue, reduces ventricular rate during AF by slowing AV conduction. Absence of this effect after ivabradine administration implicates If inhibition as a mechanism.

Dronedarone's inhibition of If current is the primary mechanism responsible for its bradycardic effect.

INTRODUCTION: The mechanism(s) whereby dronedarone reduces sinus rate are not well understood, although L-type calcium channel antagonism, beta-adrenergic blockade, and inhibition of If are plausible. METHODS AND RESULTS: In anesthetized pigs, we compared the effects of dronedarone to the prototypical If inhibitor, ivabradine, and the L-type calcium channel antagonist diltiazem on heart rate, mean arterial blood pressure (MAP), and contractility. Dronedarone's effects on the phenylephrine-induced rise in MAP and on the chronotropic response to isoproterenol were also investigated. Cumulative doses of dronedarone (0.5 mg/kg, i.v., and 5.0 mg/kg, i.v.; plasma level: 80 ± 16.1 nM) progressively reduced heart rate (P < 0.02) without changes in MAP or contractility as assessed by LV dP/dt (N = 6). Ivabradine (0.5 mg/kg, i.v.) similarly reduced heart rate (P < 0.01) without change in MAP (N = 6). Diltiazem (0.8 mg/kg, i.v.) reduced heart rate and MAP and decreased contractility (N = 6). Dronedarone blunted phenylephrine's alpha-receptor-mediated increase in MAP but did not alter the marked beta-adrenergic receptor (BAR)-mediated increase in heart rate induced by isoproterenol. When dronedarone injection was preceded by ivabradine, no further decrease in heart rate or change in MAP was observed (N = 6). CONCLUSIONS: Dronedarone reduced heart rate without affecting MAP or contractility, effects that differ from L-type calcium channel blockade. Dronedarone did not antagonize BAR stimulation, and its heart-rate lowering effects were eliminated by prior administration of ivabradine. Thus, dronedarone's bradycardic action is likely due to inhibition of If and not to blockade of either L-type calcium channels or BAR.