Fast-Track Nonelective Laparoscopic Cholecystectomy is Safe and Feasible.

INTRODUCTION: Ample evidence exists to support the safety of fast-track discharge after elective laparoscopic cholecystectomy (LC), but there is currently no data available to support the safety of fast-tracking patients undergoing nonelective LC. We sought to determine whether fast-tracking patients undergoing nonelective LC is safe and feasible. METHODS: We performed a retrospective cohort review of 661 consecutive patients undergoing LC at a single teaching institution from April 2018 to January 2020. Subjects were divided into two groups: elective LC (ELC) and fast-track nonelective LC (FTLC). FTLC was defined as nonelective LC with total length of stay <36 h. Patients undergoing nonelective LC with length of stay exceeding 36 h were excluded. The primary outcome of interest was readmission within 30 d. The secondary outcomes included incidences of return to emergency department within 30 d, retained stone, bile leak, and wound infection. RESULTS: Of 661 LC, 185 (27%) were ELC and 476 (72%) were nonelective. FTLC included 121 (25%) of the nonelective LC. Preoperative characteristics were similar among the groups. On final pathology, chronic cholecystitis was predominant in both groups, but FTLC exhibited higher rates of acute cholecystitis (P < 0.0001). There was no significant difference in the primary outcome among groups: readmission within 30 d occurred in 6 (3%) ELC patients and 4 (3%) FTLC patients (P = 1.0). There were no significant differences in rates of return to emergency department within 30 d, retained stone, bile leak, or wound infection. CONCLUSIONS: With comparable postoperative complication rates to ELC, FTLC can be safely used in select patients. Additional studies are needed to determine preoperative predictors of FTLC suitability to prospectively identify appropriate patients.

In-Person Clinic Visits After Laparoscopic Cholecystectomy: Lessons Learned From COVID-19 Pandemic.

INTRODUCTION: The utility of routine in-person clinic appointments after laparoscopic cholecystectomy (LC) is uncertain, especially after the increase of telehealth visits during the COVID-19 pandemic. The purpose of this study was to evaluate the utility of routine in-person follow-up for patients undergoing LC prior to changes implemented during the pandemic and to determine whether a return to routine in-person follow-up is warranted. METHODS: We retrospectively reviewed follow-up encounters for all patients undergoing LC from April 2018 to February 2020. All patients were routinely scheduled for in-person postoperative clinic follow-up 2-4 wk after discharge. Follow-up was considered nonroutine if new studies or medications were ordered, the patient was referred to the emergency department or readmitted, or malignancy was identified on pathology review. RESULTS: Of 661 patients undergoing LC, 449 (68%) attended their scheduled in-person postoperative appointment and 212 (32%) did not. The postoperative appointment was nonroutine for 39 patients (9% of clinic attenders). Readmission occurred in 42 patients, with no differences between clinic attenders and nonattenders (P = 0.12). Furthermore, attending a postoperative clinic visit did not affect odds of readmission (odds ratio: 0.705, 95% confidence interval: 0.368, 1.351; P = 0.29). Readmission occurred on median day 9 after discharge in both groups. CONCLUSIONS: The incidence of nonroutine follow-up after LC is low, and attendance at follow-up clinic was not associated with reduced readmissions. A return to routinely scheduling in-person follow-up 2-4 wk after discharge may not be warranted. Telehealth visits within 1 wk of discharge after LC should be considered.

A retrospective view of 2020: A unique year for Immunology.

2020 was a year unlike any other for Immunology. Through the SARS-CoV-2 pandemic, with fantastic support from the global immunology community, we worked together to reach new heights. Here, we look back at some of the highlights for Immunology in a challenging and memorable year.

Sarcoplasmic reticulum K(+) (TRIC) channel does not carry essential countercurrent during Ca(2+) release.

The charge translocation associated with sarcoplasmic reticulum (SR) Ca(2+) efflux is compensated for by a simultaneous SR K(+) influx. This influx is essential because, with no countercurrent, the SR membrane potential (Vm) would quickly (<1 ms) reach the Ca(2+) equilibrium potential and SR Ca(2+) release would cease. The SR K(+) trimeric intracellular cation (TRIC) channel has been proposed to carry the essential countercurrent. However, the ryanodine receptor (RyR) itself also carries a substantial K(+) countercurrent during release. To better define the physiological role of the SR K(+) channel, we compared SR Ca(2+) transport in saponin-permeabilized cardiomyocytes before and after limiting SR K(+) channel function. Specifically, we reduced SR K(+) channel conduction 35 and 88% by replacing cytosolic K(+) for Na(+) or Cs(+) (respectively), changes that have little effect on RyR function. Calcium sparks, SR Ca(2+) reloading, and caffeine-evoked Ca(2+) release amplitude (and rate) were unaffected by these ionic changes. Our results show that countercurrent carried by SR K(+) (TRIC) channels is not required to support SR Ca(2+) release (or uptake). Because K(+) enters the SR through RyRs during release, the SR K(+) (TRIC) channel most likely is needed to restore trans-SR K(+) balance after RyRs close, assuring SR Vm stays near 0 mV.

Nitric oxide-dependent activation of CaMKII increases diastolic sarcoplasmic reticulum calcium release in cardiac myocytes in response to adrenergic stimulation.

Spontaneous calcium waves in cardiac myocytes are caused by diastolic sarcoplasmic reticulum release (SR Ca(2+) leak) through ryanodine receptors. Beta-adrenergic (ß-AR) tone is known to increase this leak through the activation of Ca-calmodulin-dependent protein kinase (CaMKII) and the subsequent phosphorylation of the ryanodine receptor. When ß-AR drive is chronic, as observed in heart failure, this CaMKII-dependent effect is exaggerated and becomes potentially arrhythmogenic. Recent evidence has indicated that CaMKII activation can be regulated by cellular oxidizing agents, such as reactive oxygen species. Here, we investigate how the cellular second messenger, nitric oxide, mediates CaMKII activity downstream of the adrenergic signaling cascade and promotes the generation of arrhythmogenic spontaneous Ca(2+) waves in intact cardiomyocytes. Both SCaWs and SR Ca(2+) leak were measured in intact rabbit and mouse ventricular myocytes loaded with the Ca-dependent fluorescent dye, fluo-4. CaMKII activity in vitro and immunoblotting for phosphorylated residues on CaMKII, nitric oxide synthase, and Akt were measured to confirm activity of these enzymes as part of the adrenergic cascade. We demonstrate that stimulation of the ß-AR pathway by isoproterenol increased the CaMKII-dependent SR Ca(2+) leak. This increased leak was prevented by inhibition of nitric oxide synthase 1 but not nitric oxide synthase 3. In ventricular myocytes isolated from wild-type mice, isoproterenol stimulation also increased the CaMKII-dependent leak. Critically, in myocytes isolated from nitric oxide synthase 1 knock-out mice this effect is ablated. We show that isoproterenol stimulation leads to an increase in nitric oxide production, and nitric oxide alone is sufficient to activate CaMKII and increase SR Ca(2+) leak. Mechanistically, our data links Akt to nitric oxide synthase 1 activation downstream of ß-AR stimulation. Collectively, this evidence supports the hypothesis that CaMKII is regulated by nitric oxide as part of the adrenergic cascade leading to arrhythmogenesis.