Untuned antiviral immunity in COVID-19 revealed by temporal type I/III interferon patterns and flu comparison.

A central paradigm of immunity is that interferon (IFN)-mediated antiviral responses precede pro-inflammatory ones, optimizing host protection and minimizing collateral damage1,2. Here, we report that for coronavirus disease 2019 (COVID-19) this paradigm does not apply. By investigating temporal IFN and inflammatory cytokine patterns in 32 moderate-to-severe patients with COVID-19 hospitalized for pneumonia and longitudinally followed for the development of respiratory failure and death, we reveal that IFN-λ and type I IFN production were both diminished and delayed, induced only in a fraction of patients as they became critically ill. On the contrary, pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-6 and IL-8 were produced before IFNs in all patients and persisted for a prolonged time. This condition was reflected in blood transcriptomes wherein prominent IFN signatures were only seen in critically ill patients who also exhibited augmented inflammation. By comparison, in 16 patients with influenza (flu) hospitalized for pneumonia with similar clinicopathological characteristics to those of COVID-19 and 24 nonhospitalized patients with flu with milder symptoms, IFN-λ and type I IFN were robustly induced earlier, at higher levels and independently of disease severity, whereas pro-inflammatory cytokines were only acutely produced. Notably, higher IFN-λ concentrations in patients with COVID-19 correlated with lower viral load in bronchial aspirates and faster viral clearance and a higher IFN-λ to type I IFN ratio correlated with improved outcome for critically ill patients. Moreover, altered cytokine patterns in patients with COVID-19 correlated with longer hospitalization and higher incidence of critical disease and mortality compared to flu. These data point to an untuned antiviral response in COVID-19, contributing to persistent viral presence, hyperinflammation and respiratory failure.

Health system-scale language models are all-purpose prediction engines.

Physicians make critical time-constrained decisions every day. Clinical predictive models can help physicians and administrators make decisions by forecasting clinical and operational events. Existing structured data-based clinical predictive models have limited use in everyday practice owing to complexity in data processing, as well as model development and deployment1-3. Here we show that unstructured clinical notes from the electronic health record can enable the training of clinical language models, which can be used as all-purpose clinical predictive engines with low-resistance development and deployment. Our approach leverages recent advances in natural language processing4,5 to train a large language model for medical language (NYUTron) and subsequently fine-tune it across a wide range of clinical and operational predictive tasks. We evaluated our approach within our health system for five such tasks: 30-day all-cause readmission prediction, in-hospital mortality prediction, comorbidity index prediction, length of stay prediction, and insurance denial prediction. We show that NYUTron has an area under the curve (AUC) of 78.7-94.9%, with an improvement of 5.36-14.7% in the AUC compared with traditional models. We additionally demonstrate the benefits of pretraining with clinical text, the potential for increasing generalizability to different sites through fine-tuning and the full deployment of our system in a prospective, single-arm trial. These results show the potential for using clinical language models in medicine to read alongside physicians and provide guidance at the point of care.

Fractional Flow Reserve-Guided PCI as Compared with Coronary Bypass Surgery.

BACKGROUND: Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking. METHODS: In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed. RESULTS: A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group. CONCLUSIONS: In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.).

Electrical Impedance Tomography-based Ventilation Patterns in Patients after Major Surgery.

Rationale: General anesthesia and mechanical ventilation have negative impacts on the respiratory system, causing heterogeneous distribution of lung aeration, but little is known about the ventilation patterns of postoperative patients and their association with clinical outcomes. Objectives: To clarify the phenotypes of ventilation patterns along a gravitational direction after surgery by using electrical impedance tomography (EIT) and to evaluate their association with postoperative pulmonary complications (PPCs) and other relevant clinical outcomes. Methods: Adult postoperative patients at high risk for PPCs, receiving mechanical ventilation on ICU admission (N = 128), were prospectively enrolled between November 18, 2021 and July 18, 2022. PPCs were prospectively scored until hospital discharge, and their association with phenotypes of ventilation patterns was studied. The secondary outcomes were the times to wean from mechanical ventilation and oxygen use and the length of ICU stay. Measurements and Main Results: Three phenotypes of ventilation patterns were revealed by EIT: phenotype 1 (32% [n = 41], a predominance of ventral ventilation), phenotype 2 (41% [n = 52], homogeneous ventilation), and phenotype 3 (27% [n = 35], a predominance of dorsal ventilation). The median PPC score was higher in phenotype 1 and phenotype 3 than in phenotype 2. The median time to wean from mechanical ventilation was longer in phenotype 1 versus phenotype 2. The median duration of ICU stay was longer in phenotype 1 versus phenotype 2. The median time to wean from oxygen use was longer in phenotype 1 and phenotype 3 than in phenotype 2. Conclusions: Inhomogeneous ventilation patterns revealed by EIT on ICU admission were associated with PPCs, delayed weaning from mechanical ventilation and oxygen use, and a longer ICU stay.

In ICU patients not receiving early PN, tight and liberal glucose control did not differ for length of ICU stay or death.

SOURCE CITATION: Gunst J, Debaveye Y, Güiza F, et al; TGC-Fast Collaborators. Tight blood-glucose control without early parenteral nutrition in the ICU. N Engl J Med. 2023;389:1180-1190. 37754283.

A streamlined pathway for transcatheter aortic valve implantation: the BENCHMARK study.

BACKGROUND AND AIMS: There is significant potential to streamline the clinical pathway for patients undergoing transcatheter aortic valve implantation (TAVI). The purpose of this study was to evaluate the effect of implementing BENCHMARK best practices on the efficiency and safety of TAVI in 28 sites in 7 European countries. METHODS: This was a study of patients with severe symptomatic aortic stenosis (AS) undergoing TAVI with balloon-expandable valves before and after implementation of BENCHMARK best practices. Principal objectives were to reduce hospital length of stay (LoS) and duration of intensive care stay. Secondary objective was to document patient safety. RESULTS: Between January 2020 and March 2023, 897 patients were documented prior to and 1491 patients after the implementation of BENCHMARK practices. Patient characteristics were consistent with a known older TAVI population and only minor differences. Mean LoS was reduced from 7.7 ± 7.0 to 5.8 ± 5.6 days (median 6 vs. 4 days; P < .001). Duration of intensive care was reduced from 1.8 to 1.3 days (median 1.1 vs. 0.9 days; P < .001). Adoption of peri-procedure best practices led to increased use of local anaesthesia (96.1% vs. 84.3%; P < .001) and decreased procedure (median 47 vs. 60 min; P < .001) and intervention times (85 vs. 95 min; P < .001). Thirty-day patient safety did not appear to be compromised with no differences in all-cause mortality (0.6% in both groups combined), stroke/transient ischaemic attack (1.4%), life-threatening bleeding (1.3%), stage 2/3 acute kidney injury (0.7%), and valve-related readmission (1.2%). CONCLUSIONS: Broad implementation of BENCHMARK practices contributes to improving efficiency of TAVI pathway reducing LoS and costs without compromising patient safety.

Reducing length of stay after transfemoral transcatheter aortic valve implantation: the FAST-TAVI II trial.

BACKGROUND AND AIMS: The length of stay (LOS) after transcatheter aortic valve implantation (TAVI) remains extremely variable whereas early discharge has been shown to be feasible and safe. The study objective was to evaluate the efficacy and safety of an intervention aimed at reducing LOS after transfemoral TAVI. METHODS: FAST-TAVI II is a prospective, multicentre, cluster, randomized, controlled study including patients with severe symptomatic aortic stenosis, who had transfemoral TAVI. The intervention consisted in a dedicated training programme to implement 10 quality of care measures to reduce LOS with an implementation phase of eight weeks. The primary endpoint was the proportion of patients discharged early within 3 days. Secondary endpoints included: LOS, 30-day mortality and 30-day incidence of readmission for cardiovascular events. RESULTS: During the study period, 969 patients were enrolled in the intervention group and 860 patients in the control group. Mean age was 81.9 ± 6.6 years and mean EuroSCORE II was 4.4 ± 4.5%. Early discharge was achieved in 563 (58.1%) patients in the intervention group vs. 364 (42.3%) patients in the control group (P < .0001). Median LOS was significantly reduced in the intervention group compared to the control group [3 (IQR: 3) vs. 4 days (IQR: 3), P < .0001]. Thirty-day mortality was low and similar in the two groups (0.5% vs. 0.9%, P = .30), as were 30-day readmissions (4.6% vs. 2.8%, P = .28). CONCLUSIONS: The intervention was simple and fast to implement, and was effective and safe to reduce LOS and increase the proportion of patients discharged early after TAVI (NCT04503655).

Effect of Exercise Training on Prognosis in Community-acquired Pneumonia: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effect of standard care (SoC) combined with supervised in-bed cycling (Bed-Cycle) or booklet exercises (Book-Exe) versus SoC in community-acquired pneumonia (CAP). METHODS: In this randomized controlled trial, 186 patients with CAP were assigned to SoC (n = 62), Bed-Cycle (n = 61), or Book-Exe (n = 63). Primary outcome length of stay (LOS) was analyzed with analysis of covariance. Secondary outcomes, 90-day readmission, and 180-day mortality were analyzed with Cox proportional hazard regression and readmission days with negative-binominal regression. RESULTS: LOS was -2% (95% CI: -24 to 25) and -1% (95% CI: -22 to 27) for Bed-Cycle and Book-Exe, compared with SoC. Ninety-day readmission was 35.6% for SoC, 27.6% for Bed-Cycle, and 21.3% for Book-Exe. Adjusted hazard ratio (aHR) for 90-day readmission was 0.63 (95% CI: .33-1.21) and 0.54 (95% CI: .27-1.08) for Bed-Cycle and Book-Exe compared with SoC. aHR for 90-day readmission for combined exercise was 0.59 (95% CI: .33-1.03) compared with SoC. aHR for 180-day mortality was 0.84 (95% CI: .27-2.60) and 0.82 (95% CI: .26-2.55) for Bed-Cycle and Book-Exe compared with SoC. Number of readmission days was 226 for SoC, 161 for Bed-Cycle, and 179 for Book-Exe. Incidence rate ratio for readmission days was 0.73 (95% CI: .48-1.10) and 0.77 (95% CI: .51-1.15) for Bed-Cycle and Book-Exe compared with SoC. CONCLUSIONS: Although supervised exercise training during admission with CAP did not reduce LOS or mortality, this trial suggests its potential to reduce readmission risk and number of readmission days. CLINICAL TRIALS REGISTRATION: NCT04094636.

Characterizing the burden of biliary tract cancers across 28 hospitals in Ontario, Canada.

BACKGROUND AND AIMS: The incidence of biliary tract cancers (BTC) appears to be increasing worldwide. We analyzed the characteristics of BTC-related hospitalizations under medical services across 28 hospitals in Ontario, Canada. METHODS: This study uses data collected by GEMINI, a hospital research data network. BTC-related hospitalizations from 2015 to 2021 under the Department of Medicine or intensive care unit were captured using the International Classification of Diseases, 10th revision, codes for intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma, and gallbladder cancers. RESULTS: A total of 4596 BTC-related hospitalizations (2720 iCCA, 1269 extrahepatic cholangiocarcinoma, 607 gallbladder cancers) were analyzed. The number of unique patients with BTC-related hospitalizations increased over time. For iCCA-related hospitalizations, the total number of hospitalizations increased (from 385 in 2016 to 420 in 2021, p = .005), the hospital length of stay decreased over the study period (mean 10 days [SD, 12] in 2016 to 9 days [SD, 8] in 2021, p = .04), and the number of in-hospital deaths was stable (from 68 [18%] in 2016 to 55 [13%] in 2021, p = .62). Other outcomes such as 30-day readmissions, medical imaging tests, intensive care unit-specific hospitalizations, and length of stay were stable over time for all cohorts. The cost of hospitalization for the BTC cohort increased from median $8203 CAD (interquartile range, 5063-15,543) in 2017 to $8507 CAD (interquartile range, 5345-14,755) in 2021. CONCLUSIONS: This real-world data analysis showed a rising number of patients with BTC-related hospitalizations and rising number of iCCA-related hospitalizations across 28 hospitals in Ontario between 2015 and 2021.

Centralization of Pancreaticoduodenectomy: A Systematic Review and Spline Regression Analysis to Recommend Minimum Volume for a Specialist Pancreas Service.

OBJECTIVE: Through a systematic review and spline curve analysis, to better define the minimum volume threshold for hospitals to perform (pancreaticoduodenectomy) and the high-volume center. BACKGROUND: The pancreaticoduodenectomy (PD) is a resource-intensive procedure, with high morbidity and long hospital stays resulting in centralization towards high-volume hospitals; the published definition of high volume remains variable. MATERIALS AND METHODS: Following a systematic review of studies comparing PD outcomes across volume groups, semiparametric regression modeling of morbidity (%), mortality (%), length of stay (days), lymph node harvest (number of nodes), and cost ($USD) as continuous variables were performed and fitted as a smoothed function of splines. If this showed a nonlinear association, then a "zero-crossing" technique was used, which produced "first and second derivatives" to identify volume thresholds. RESULTS: Our analysis of 33 cohort studies (198,377 patients) showed 55 PDs/year and 43 PDs/year were the threshold value required to achieve the lowest morbidity and highest lymph node harvest, with model estimated df 5.154 ( P <0.001) and 8.254 ( P <0.001), respectively. The threshold value for mortality was ~45 PDs/year (model 9.219 ( P <0.001)), with the lowest mortality value (the optimum value) at ~70 PDs/year (ie, a high-volume center). No significant association was observed for cost ( edf =2, P =0.989) and length of stay ( edf =2.04, P =0.099). CONCLUSIONS: There is a significant benefit from the centralization of PD, with 55 PDs/year and 43 PDs/year as the threshold value required to achieve the lowest morbidity and highest lymph node harvest, respectively. To achieve mortality benefit, the minimum procedure threshold is 45 PDs/year, with the lowest and optimum mortality value (ie, a high-volume center) at approximately 70 PDs/year.

Clinical Impact of an Enhanced Recovery Program for Lower-extremity Bypass.

OBJECTIVE: To determine the association of Enhanced Recovery Program (ERP) implementation with length of stay (LOS) and perioperative outcomes after lower-extremity bypass (LEB). BACKGROUND: ERPs have been shown to decrease hospital LOS and improve perioperative outcomes, but their impact on patients undergoing vascular surgery remains unknown. METHODS: Patients undergoing LEB who received or did not receive care under the ERP were included; pre-ERP (January 1, 2016-May 13, 2018) and ERP (May 14, 2018-July 31, 2022). Clinicopathologic characteristics and perioperative outcomes were analyzed. RESULTS: Of 393 patients who underwent LEB [pre-ERP: n = 161 (41%); ERP: n = 232 (59%)], most were males (n = 254, 64.6%), White (n = 236, 60%), and government-insured (n = 265, 67.4%). Pre-ERP patients had higher Body Mass Index (28.8 ± 6.0 vs 27.4 ± 5.7, P = 0.03) and rates of diabetes (52% vs 36%, P = 0.002). ERP patients had a shorter total [6 (3-13) vs 7 (5-14) days, P = 0.01) and postoperative LOS [5 (3-8) vs 6 (4-8) days, P < 0.001]. Stratified by indication, postoperative LOS was shorter in ERP patients with claudication (3 vs 5 days, P = 0.01), rest pain (5 vs 6 days, P = 0.02), and tissue loss (6 vs 7 days, P = 0.03). ERP patients with rest pain also had a shorter total LOS (6 vs 7 days, P = 0.04) and lower 30-day readmission rates (32%-17%, P = 0.02). After ERP implementation, the average daily oral morphine equivalents decreased [median (interquartile range): 52.5 (26.6-105.0) vs 44.12 (22.2-74.4), P = 0.019], while the rates of direct discharge to home increased (83% vs 69%, P = 0.002). CONCLUSIONS: This is the largest single-center cohort study evaluating ERP in LEB, showing that ERP implementation is associated with shorter LOS and improved perioperative outcomes.

Study of Risk Factors for Readmission After Pancreatectomy for Cancer: Analysis of Nationwide Cohort.

OBJECTIVE: To identify the factors associated with readmission after pancreatectomy for cancer and to assess their impact on the 1-year mortality in a French multicentric population. BACKGROUND: Pancreatectomy is a complex procedure with high morbidity that increases the length of hospital stay and jeopardizes survival. Hospital readmissions lead to increased health system costs, making this a topic of great interest. METHODS: Data collected from patients who underwent pancreatectomy for cancer between 2011 and 2019 were extracted from a French national medico-administrative database. A descriptive analysis was conducted to evaluate the association of baseline variables, including age, sex, liver-related comorbidities, Charlson Comorbidity Index, tumor localization, and use of neoadjuvant therapy, along with hospital type and volume, with readmission status. Centers were divided into low and high volumes according to the cutoff of 26 cases/year. Logistic regression models were developed to determine whether the identified bivariate associations persisted after adjusting for the patient characteristics. The mortality rates during readmission and at 1 year postoperatively were also determined. RESULTS: Of 22,935 patients who underwent pancreatectomy, 9129 (39.3%) were readmitted within 6 months. Readmission rates by year did not vary over the study period, and mean readmissions occurred within 20 days after discharge. Multivariate analysis showed that male sex [odds ratio (OR) = 1.12], age >70 years (OR = 1.16), comorbidities (OR = 1.21), distal pancreatectomy (OR = 1.11), and major postoperative complications (OR = 1.37) were predictors of readmission. Interestingly, readmission and surgery in low-volume centers increased the risk of death at 1 year by a factor of 2.15 [(2.01-2.31), P < 0.001] and 1.31 [(1.17-1.47), P < 0.001], respectively. CONCLUSIONS: Readmission after pancreatectomy for cancer is high with an increased rate of 1-year mortality.

Effect of Laparoscopic and Open Pancreaticoduodenectomy for Pancreatic or Periampullary Tumors: Three-year Follow-up of a Randomized Clinical Trial.

OBJECTIVE: This study aimed to estimate whether the potential short-term advantages of laparoscopic pancreaticoduodenectomy (LPD) could allow patients to recover in a more timely manner and achieve better long-term survival than with open pancreaticoduodenectomy (OPD) in patients with pancreatic or periampullary tumors. BACKGROUND: LPD has been demonstrated to be feasible and may have several potential advantages over OPD in terms of shorter hospital stay and accelerated recovery than OPD. METHODS: This noninferiority, open-label, randomized clinical trial was conducted in 14 centers in China. The initial trial included 656 eligible patients with pancreatic or periampullary tumors enrolled from May 18, 2018, to December 19, 2019. The participants were randomized preoperatively in a 1:1 ratio to undergo either LPD (n=328) or OPD (n=328). The 3-year overall survival (OS), quality of life, which was assessed using the 3-level version of the European Quality of Life-5 Dimensions, depression, and other outcomes were evaluated. RESULTS: Data from 656 patients [328 men (69.9%); mean (SD) age: 56.2 (10.7) years] who underwent pancreaticoduodenectomy were analyzed. For malignancies, the 3-year OS rates were 59.1% and 54.3% in the LPD and OPD groups, respectively ( P =0.33, hazard ratio: 1.16, 95% CI: 0.86-1.56). The 3-year OS rates for others were 81.3% and 85.6% in the LPD and OPD groups, respectively ( P =0.40, hazard ratio: 0.70, 95% CI: 0.30-1.63). No significant differences were observed in quality of life, depression and other outcomes between the 2 groups. CONCLUSION: In patients with pancreatic or periampullary tumors, LPD performed by experienced surgeons resulted in a similar 3-year OS compared with OPD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03138213.

Anatomic Lung Resection Outcomes After Implementation of a Universal Thoracic ERAS Protocol Across a Diverse Health Care System.

OBJECTIVE: We sought to evaluate how implementing a thoracic enhanced recovery after surgery (ERAS) protocol impacted surgical outcomes after elective anatomic lung resection. BACKGROUND: The effect of implementing the ERAS Society/European Society of Thoracic Surgery thoracic ERAS protocol on postoperative outcomes throughout an entire health care system has not yet been reported. METHODS: This was a prospective cohort study within one health care system (January 2019-March, 2023). A thoracic ERAS protocol was implemented on May 1, 2021 for elective anatomic lung resections, and postoperative outcomes were tracked using the electronic health record and Vizient data. The primary outcome was overall morbidity; secondary outcomes included individual complications, length of stay, opioid use, chest tube duration, and total cost. Patients were grouped into pre-ERAS and post-ERAS cohorts. Bivariable comparisons were performed using independent t -test, χ 2 , or Fisher exact tests, and multivariable logistic regression was performed to control for confounders. RESULTS: There were 1007 patients in the cohort; 450 (44.7%) were in the post-ERAS group. Mean age was 66.2 years; most patients were female (65.1%), white (83.8%), had a body mass index between 18.5 and 29.9 (69.7%), and were ASA class 3 (80.6%). Patients in the postimplementation group had lower risk-adjusted rates of any morbidity, respiratory complication, pneumonia, surgical site infection, arrhythmias, infections, opioid usage, ICU use, and shorter postoperative length of stay (all P <0.05). CONCLUSIONS: Postoperative outcomes were improved after the implementation of an evidence-based thoracic ERAS protocol throughout the health care system. This study validates the ERAS Society/European Society of Thoracic Surgery guidelines and demonstrates that simultaneous multihospital implementation can be feasible and effective.

Propensity Score-Matching Analysis Comparing Robotic Versus Laparoscopic Limited Liver Resections of the Posterosuperior Segments: An International Multicenter Study.

OBJECTIVE: The purpose of this study was to compare the outcomes of robotic limited liver resections (RLLR) versus laparoscopic limited liver resections (LLLR) of the posterosuperior segments. BACKGROUND: Both laparoscopic and robotic liver resections have been used for tumors in the posterosuperior liver segments. However, the comparative performance and safety of both approaches have not been well examined in the existing literature. METHODS: This is a post hoc analysis of a multicenter database of 5446 patients who underwent RLLR or LLLR of the posterosuperior segments (I, IVa, VII, and VIII) at 60 international centers between 2008 and 2021. Data on baseline demographics, center experience and volume, tumor features, and perioperative characteristics were collected and analyzed. Propensity score-matching (PSM) analysis (in both 1:1 and 1:2 ratios) was performed to minimize selection bias. RESULTS: A total of 3510 cases met the study criteria, of whom 3049 underwent LLLR (87%), and 461 underwent RLLR (13%). After PSM (1:1: and 1:2), RLLR was associated with a lower open conversion rate [10 of 449 (2.2%) vs 54 of 898 (6.0%); P =0.002], less blood loss [100 mL [IQR: 50-200) days vs 150 mL (IQR: 50-350); P <0.001] and a shorter operative time (188 min (IQR: 140-270) vs 222 min (IQR: 158-300); P <0.001]. These improved perioperative outcomes associated with RLLR were similarly seen in a subset analysis of patients with cirrhosis-lower open conversion rate [1 of 136 (0.7%) vs 17 of 272 (6.2%); P =0.009], less blood loss [100 mL (IQR: 48-200) vs 160 mL (IQR: 50-400); P <0.001], and shorter operative time [190 min (IQR: 141-258) vs 230 min (IQR: 160-312); P =0.003]. Postoperative outcomes in terms of readmission, morbidity and mortality were similar between RLLR and LLLR in both the overall PSM cohort and cirrhosis patient subset. CONCLUSIONS: RLLR for the posterosuperior segments was associated with superior perioperative outcomes in terms of decreased operative time, blood loss, and open conversion rate when compared with LLLR.

Nationwide use and Outcome of Minimally Invasive Distal Pancreatectomy in IDEAL Stage IV following a Training Program and Randomized Trial.

OBJECTIVE: To assess the nationwide long-term uptake and outcomes of minimally invasive distal pancreatectomy (MIDP) after a nationwide training program and randomized trial. BACKGROUND: Two randomized trials demonstrated the superiority of MIDP over open distal pancreatectomy (ODP) in terms of functional recovery and hospital stay. Data on implementation of MIDP on a nationwide level are lacking. METHODS: Nationwide audit-based study including consecutive patients after MIDP and ODP in 16 centers in the Dutch Pancreatic Cancer Audit (2014 to 2021). The cohort was divided into three periods: early implementation, during the LEOPARD randomized trial, and late implementation. Primary endpoints were MIDP implementation rate and textbook outcome. RESULTS: Overall, 1496 patients were included with 848 MIDP (56.5%) and 648 ODP (43.5%). From the early to the late implementation period, the use of MIDP increased from 48.6% to 63.0% and of robotic MIDP from 5.5% to 29.7% ( P <0.001). The overall use of MIDP (45% to 75%) and robotic MIDP (1% to 84%) varied widely between centers ( P <0.001). In the late implementation period, 5/16 centers performed >75% of procedures as MIDP. After MIDP, in-hospital mortality and textbook outcome remained stable over time. In the late implementation period, ODP was more often performed in ASA score III-IV (24.9% vs. 35.7%, P =0.001), pancreatic cancer (24.2% vs. 45.9%, P <0.001), vascular involvement (4.6% vs. 21.9%, P <0.001), and multivisceral involvement (10.5% vs. 25.3%, P <0.001). After MIDP, shorter hospital stay (median 7 vs. 8 d, P <0.001) and less blood loss (median 150 vs. 500 mL, P <0.001), but more grade B/C postoperative pancreatic fistula (24.4% vs. 17.2%, P =0.008) occurred as compared to ODP. CONCLUSION: A sustained nationwide implementation of MIDP after a successful training program and randomized trial was obtained with satisfactory outcomes. Future studies should assess the considerable variation in the use of MIDP between centers and, especially, robotic MIDP.

Intercostal Nerve Cryoablation Reduces Opioid Use and Length of Stay Without Increasing Adverse Events: A Retrospective Cohort Study of 5442 Patients Undergoing Surgical Correction of Pectus Excavatum.

OBJECTIVE: To examine differences in opioid use, length of stay, and adverse events after minimally invasive correction of pectus excavatum (MIRPE) with and without intercostal nerve cryoablation. BACKGROUND: Small studies show that intraoperative intercostal nerve cryoablation provides effective analgesia with no large-scale evaluations of this technique. METHODS: The pediatric health information system database was used to perform a retrospective cohort study comparing patients undergoing MIRPE at children's hospitals before and after the initiation of cryoablation. The association of cryoablation use with inpatient opioid use was determined using quantile regression with robust standard errors. Difference in risk-adjusted length of stay between the cohorts was estimated using negative binomial regression. Odds of adverse events between the two cohorts were compared using logistic regression with a generalized estimating equation. RESULTS: A total of 5442 patients underwent MIRPE at 44 children's hospitals between 2016 and 2022 with 1592 patients treated after cryoablation was introduced at their hospital. Cryoablation use was associated with a median decrease of 80.8 (95% CI: 68.6-93.0) total oral morphine equivalents as well as a decrease in estimated median length of stay from 3.5 [3.2-3.9] days to 2.5 [2.2-2.9] days ( P value: 0.016). Cryoablation use was not significantly associated with an increase in any studied adverse events. CONCLUSIONS: Introduction of cryoablation for perioperative analgesia was associated with decreased inpatient opioid use and length of stay in a large sample with no change in adverse events. This novel modality for perioperative analgesia offers a promising alternative to traditional pain management in thoracic surgery.

Two Days Versus Five Days of Postoperative Antibiotics for Complex Appendicitis: Cost Analysis of a Randomized, Noninferiority Trial.

OBJECTIVE: To compare costs for 2 days versus 5 days of postoperative antibiotics within the antibiotics after an aPPendectomy In Complex appendicitis trial.Background:Recent studies suggest that restrictive antibiotic use leads to a significant reduction in hospital stays without compromising patient safety. Its potential effect on societal costs remains underexplored. METHODS: This was a pragmatic, open-label, multicenter clinical trial powered for noninferiority. Patients with complex appendicitis (age ≥ 8 years) were randomly allocated to 2 days or 5 days of intravenous antibiotics after appendectomy. Patient inclusion lasted from June 2017 to June 2021 in 15 Dutch hospitals. The final follow-up was on September 1, 2021. The primary trial endpoint was a composite endpoint of infectious complications and mortality within 90 days. In the present study, the main outcome measures were overall societal costs (comprising direct health care costs and costs related to productivity loss) and cost-effectiveness. Direct health care costs were recorded based on data in the electronic patient files, complemented by a telephone follow-up at 90 days. In addition, data on loss of productivity were acquired through the validated Productivity Cost Questionnaire at 4 weeks after surgery. Cost estimates were based on prices for the year 2019. RESULTS: In total, 1005 patients were evaluated in the "intention-to-treat" analysis: 502 patients were allocated to the 2-day group and 503 to the 5-day group. The mean difference in overall societal costs was - €625 (95% CI: -€ 958 to -€ 278) to the advantage of the 2-day group. This difference was largely explained by reduced hospital stay. Productivity losses were similar between the study groups. Restricting postoperative antibiotics to 2 days was cost-effective, with estimated cost savings of €31,117 per additional infectious complication. CONCLUSIONS: Two days of postoperative antibiotics for complex appendicitis results in a statistically significant and relevant cost reduction, as compared with 5 days. Findings apply to laparoscopic appendectomy in a well-resourced health care setting.

Early Interventional Treatment of High Output Chyle Leak After Esophagectomy is Associated With Improved Survival.

OBJECTIVE: To investigate overall survival and length of stay (LOS) associated with differing management for high output (>1 L over 24 hours) leaks (HOCL) after cancer-related esophagectomy. BACKGROUND: Although infrequent, chyle leak after esophagectomy is an event that can lead to significant perioperative sequelae. Low-volume leaks appear to respond to nonoperative measures, whereas HOCLs often require invasive therapeutic interventions. METHODS: From a prospective single-institution database, we retrospectively reviewed patients treated from 2001 to 2021 who underwent esophagectomy for esophageal cancer. Within that cohort, we focused on a subgroup of patients who manifested a HOCL postoperatively. Clinicopathologic and operative characteristics were collected, including hospital LOS and survival data. RESULTS: A total of 53/2299 patients manifested a HOCL. These were mostly males (77%), with a mean age of 62 years. Of this group, 15 patients received nonoperative management, 15 patients received prompt (<72 hours from diagnosis) interventional management, and 23 received late interventional management. Patients in the late intervention group had longer LOSs compared with early intervention (slope = 9.849, 95% CI: 3.431-16.267). Late intervention (hazard ratio: 4.772, CI: 1.384-16.460) and nonoperative management (hazard ratio: 4.731, CI: 1.294-17.305) were associated with increased mortality compared with early intervention. Patients with early intervention for HOCL had an overall survival similar to patients without chyle leaks in survival analysis. CONCLUSIONS: Patients with HOCL should receive early intervention to possibly reverse the prognostic implications of this potentially detrimental complication.

Temporary Portocaval Shunt Provides Superior Intraoperative Hemodynamics and Reduces Blood Loss and Duration of Surgery in Live Donor Liver Transplantation: A Randomized Control Trial.

OBJECTIVE: To compare intraoperative hemodynamic parameters, blood loss, renal function, and duration of surgery with and without temporary portocaval shunt (TPCS) in live donor liver transplantation (LT) recipients. Secondary objectives were postoperative early graft dysfunction, morbidity, mortality, total intensive care unit, and hospital stay. BACKGROUND: Blood loss during recipient hepatectomy for LT remains a major concern. Routine use of TPCS during LT is not yet elucidated. METHODS: This study is a single-center, open-label, randomized control trial. The sample size was calculated based on intraoperative blood loss. After exclusion, a total of 60 patients, 30 in each arm (TPCS vs no TPCS) were recruited in the trial. RESULTS: The baseline recipient and donor characteristics were comparable between the groups. The median intraoperative blood loss ( P = 0.004) and blood product transfusions ( P < 0.05) were significantly less in the TPCS group. The TPCS group had significantly improved intraoperative hemodynamics in the anhepatic phase as compared with the no TPCS group ( P < 0.0001), requiring significantly less vasopressor support. This led to significantly better renal function as evidenced by higher intraoperative urine output in the TPCS group ( P = 0.002). Because of technical simplicity, the TPCS group had significantly fewer inferior vena cava injuries (3.3 vs 26.7%, P = 0.026) and substantially shorter hepatectomy time and total duration of surgery (529.4 ± 35.54 vs 606.83 ± 48.13 min, P < 0.0001). The time taken for normalization of lactate in the immediate postoperative period was significantly shorter in the TPCS group (median, 6 vs 13 h; P = 0.04). Although postoperative endotoxemia, major morbidity, 90-day mortality, total intensive care unit, and hospital stay were comparable between both groups, tolerance to enteral feed was earlier in the TPCS group. CONCLUSIONS: In live donor LT, TPCS is a simple and effective technique that provides superior intraoperative hemodynamics and reduces blood loss and duration of surgery.