Robotic management of primary cholecystoduodenal fistula: A case report and brief literature review.

BACKGROUND: Cholecystoduodenal fistula (CDF) arises from persistent biliary tree disorders, causing fusion between the gallbladder and duodenum. Initially, open resection was common until laparoscopic fistula closure gained popularity. However, complexities within the gallbladder fossa yielded inconsistent outcomes. Advanced imaging and robotic surgery now enhance precision and detection. METHOD: A 62-year-old woman with chronic cholangitis attributed to cholecystoduodenal fistula underwent successful robotic cholecystectomy and fistula closure. RESULTS: Postoperatively, the symptoms subsided with no complications during the robotic procedure. Existing studies report favourable outcomes for robotic cholecystectomy and fistula closure. CONCLUSIONS: Our case report showcases a rare instance of successful robotic cholecystectomy with CDF closure. This case, along with a review of previous cases, suggests the potential of robotic surgery as the preferred approach, especially for patients anticipated to face significant laparoscopic morbidity.

Risk factors for readmission after a cholecystectomy: a case-control study.

OBJECTIVE: The aim of this study was to assess the risk factors associated with 30-day hospital readmissions after a cholecystectomy. METHODS: We conducted a case-control study, with data obtained from UC-Christus from Santiago, Chile. All patients who underwent a cholecystectomy between January 2015 and December 2019 were included in the study. We identified all patients readmitted after a cholecystectomy and compared them with a randomized control group. Univariate and multivariate analyses were conducted to identify risk factors. RESULTS: Of the 4866 cholecystectomies performed between 2015 and 2019, 79 patients presented 30-day hospital readmission after the surgical procedure (1.6%). We identified as risk factors for readmission in the univariate analysis the presence of a solid tumor at the moment of cholecystectomy (OR = 7.58), high pre-operative direct bilirubin (OR = 2.52), high pre-operative alkaline phosphatase (OR = 3.25), emergency admission (OR = 2.04), choledocholithiasis on admission (OR = 4.34), additional surgical procedure during the cholecystectomy (OR = 4.12), and post-operative complications. In the multivariate analysis, the performance of an additional surgical procedure during cholecystectomy was statistically significant (OR = 4.24). CONCLUSION: Performing an additional surgical procedure during cholecystectomy was identified as a risk factor associated with 30-day hospital readmission.

OBJETIVO: El objetivo de este estudio fue evaluar los factores de riesgo asociados al reingreso hospitalario en los primeros 30 días post colecistectomía. MÉTODOS: Estudio de casos-controles con datos obtenidos del Hospital Clínico de la UC-Christus, Santiago, Chile. Se ­incluyeron las colecistectomías realizadas entre los años 2015-2019. Se consideraron como casos aquellos pacientes que reingresaron en los 30 primeros días posterior a una colecistectomía. Se realizó un análisis univariado y multivariado de diferentes posibles factores de riesgo. RESULTADOS: De un total de 4866 colecistectomías, 79 pacientes presentaron reingreso hospitalario. Los resultados estadísticamente significativos en el análisis univariado fueron; tumor sólido al momento de la colecistectomía (OR = 7.58) bilirrubina directa preoperatoria alterada (OR = 2.52), fosfatasa alcalina preoperatoria alterada (OR = 3.25), ingreso de urgencia (OR = 2.04), coledocolitiasis al ingreso (OR = 4.34) realización de otros procedimientos (OR = 4.12) y complicaciones postoperatorias. En el análisis multivariado sólo la realización de otro procedimiento durante la colecistectomía fue estadísticamente significativa (OR = 4.24). CONCLUSIÓN: La realización de otros procedimientos durante la colecistectomía es un factor de riesgo de reingreso hospitalario en los 30 días posteriores a la colecistectomía.

Gallstone formation and subsequent cholecystectomy after oncological gastric and esophageal resection.

PURPOSE: Gallstone formation is increased after gastric (GR) or esophageal resection (ER); however, the exact pathophysiology is not fully understood yet. Symptomatic cholecystolithiasis and the need for subsequent cholecystectomy after upper gastrointestinal resection can alter the outcome in oncological patients. There is an ongoing discussion if these patients benefit from a simultaneous prophylactic cholecystectomy. This study aims to analyze the risk of gallstone formation after GR or ER and the perioperative course of a subsequent cholecystectomy. METHODS: In this study, all patients were included, who underwent an oncological gastric or esophageal resection at the Medical University of Innsbruck, Department of Visceral, Transplant and Thoracic Surgery in the years 2003-2021. RESULTS: A simultaneous cholecystectomy was performed in 29.8% with GR and in 2.1% with ER (p < 0.001). There was no significant difference in complications or length-of-stay between patients with simultaneous vs. no simultaneous cholecystectomy. Newly developed gallstones tended to be more common after GR (16% vs. 10% ER), after reconstruction without preservation of the duodenal passage (17% vs. 11% with) and after GR with lymph node dissection (19% vs. 5% without). After ER, subsequent cholecystectomy was significant less frequently (11.4% vs. 2.9% OR) (p = 0.005). The subsequent cholecystectomy was performed openly in 57.1% with major complications classified as Clavien-Dindo ≥ 3a in 14.3%. CONCLUSION: Based on the findings of our study, we do not recommend simultaneous cholecystectomy routinely in oncological gastric or esophageal resections. An individualized approach depending on risk factors like extensive lymphadenectomy or duodenal passage can be discussed.

Associations of cholecystectomy with metabolic health changes and incident cardiovascular disease: a retrospective cohort study.

Although some studies conducted about the risk of cholecystectomy and cardiovascular disease, there was a limit to explaining the relationship. We investigated the short-term and long-term relationship between cholecystectomy and cardiovascular disease, and evidence using the elements of the metabolic index as an intermediate step. It was a retrospective cohort study and we used the National Health Insurance Service database of South Korea between 2002 and 2015. Finally, 5,210 patients who underwent cholecystectomy and 49,457 at 1:10 age and gender-matched controls of subjects were collected. The main results was estimated by Multivariate Cox proportional hazard regression to calculate the hazard ratio (HR) with 95% confidence interval (CI) for risk of cardiovascular disease after cholecystectomy. Regarding short-term effects of cholecystectomy, increased risk of cardiovascular disease (aHR 1.35, 95% CI 1.15-1.58) and coronary heart disease (aHR 1.77, 95% CI 1.44-2.16) were similarly seen within 2 years of surgery. When analyzing the change in metabolic risk factors, cholecystectomy was associated with a change in systolic blood pressure (adjusted mean [aMean]: 1.51, 95% CI: [- 1.50 to - 4.51]), total cholesterol (aMean - 14.14, [- 20.33 to 7.95]) and body mass index (aMean - 0.13, [- 0.37 to 0.11]). Cholecystectomy patients had elevated risk of cardiovascular disease in the short-term, possibly due to the characteristics of the patient before surgery. The association of cholecystectomy and cardiovascular disease has decreased after 2 years in patients who underwent cholecystectomy, suggesting that because of improvement of metabolic health, cholecystectomy-associated elevation of cardiovascular disease risk may be ameliorated 2 years after cholecystectomy.

Social Determinants of Health Associated With the Need for Urgent Versus Elective Cholecystectomy at an Urban, Safety-Net Hospital.

Background: Benign gallstone disease is the most frequent indication for cholecystectomy in the United States. Many patients present with complicated disease requiring urgent interventions, which increases morbidity and mortality. We investigated the association between individual and population-level social determinants of health (SDoH) with urgent versus elective cholecystectomy. Patients and Methods: All patients undergoing cholecystectomy (2014-2021) for benign gallstone disease were included. Demographic and clinical data were linked to population-level SDoH characteristics using census tracts. Data were analyzed using descriptive and inferential statistics. Results: A total of 3,197 patients met inclusion criteria; 1,913 (59.84%) underwent urgent cholecystectomy, 1,204 (37.66%) underwent emergent cholecystectomy, and 80 (2.5%) underwent interval cholecystectomy. On multinomial logistic regression, patients who were older (relative risk [RR], 1.010; p < 0.001), black (RR, 1.634; p = 0.008), and living in census tracts with a higher percent of poverty (RR, 0.017; p = 0.021) had a higher relative risk of presenting for urgent cholecystectomy. Patients who were female (RR, 0.462; p < 0.001), had a primary care provider (PCP; RR, 0.821; p = 0.018), and lived in census tracts with low supermarket access (RR, 0.764; p = 0.038) had a lower relative risk of presenting for urgent cholecystectomy. Only age (RR, 1.066; p < 0.001), female gender (RR, 0.227; p < 0.001), and having a PCP (RR, 1.984; p = 0.034) were associated with presentation for interval cholecystectomy. Conclusions: Patients who were older, black, and living in census tracts with high poverty levels had a higher relative risk of presenting for urgent cholecystectomy at our institution, whereas females and patients with PCPs were more likely to undergo elective cholecystectomy. Improved access to primary care and surgical clinics for all patients at safety-net hospitals may result in improved outcomes in the management of benign gallstone disease by increasing diagnosis and treatment in the elective setting.

Percutaneous cholecystostomy in elderly patients with acute cholecystitis: a systematic review and meta-analysis.

Percutaneous cholecystostomy (PC) is often preferred over early cholecystectomy (EC) for elderly patients presenting with acute cholecystitis (AC). However, there is a lack of solid data on this issue. Following the PRISMA guidelines, we searched the Medline and Web of Science databases for reports published before December 2022. Studies that assessed elderly patients (aged 65 years and older) with AC treated using PC, in comparison with those treated with EC, were included. Outcomes analyzed were perioperative outcomes and readmissions. The literature search yielded 3279 records, from which 7 papers (1208 patients) met the inclusion criteria. No clinical trials were identified. Patients undergoing PC comprised a higher percentage of cases with ASA III or IV status (OR 3.49, 95%CI 1.59-7.69, p = 0.009) and individuals with moderate to severe AC (OR 1.78, 95%CI 1.00-3.16, p = 0.05). No significant differences were observed in terms of mortality and morbidity. However, patients in the PC groups exhibited a higher rate of readmissions (OR 3.77, 95%CI 2.35-6.05, p < 0.001) and a greater incidence of persistent or recurrent gallstone disease (OR 12.60, 95%CI 3.09-51.38, p < 0.001). Elderly patients selected for PC, displayed greater frailty and more severe AC, but did not exhibit increased post-interventional morbidity and mortality compared to those undergoing EC. Despite their inferior life expectancy, they still presented a greater likelihood of persistent or recurrent disease compared to the control group.

Post-cholecystectomy bile duct injuries: a retrospective cohort study.

BACKGROUND: Bile duct injury (BDI) is still a major worrisome complication that is feared by all surgeons undergoing cholecystectomy. The overall incidence of biliary duct injuries falls between 0.2 and 1.3%. BDI classification remains an important method to define the type of injury conducted for investigation and management. Recently, a Consensus has been taken to define BDI using the ATOM classification. Early management brings better results than delayed management. The current perspective in biliary surgery is the laparoscopic role in diagnosing and managing BDI. Diagnostic laparoscopy has been conducted in various entities for diagnostic and therapeutic measures in minor and major BDIs. METHODS: 35 cases with iatrogenic BDI following cholecystectomy (after both open and laparoscopic approaches) both happened in or were referred to Alexandria Main University Hospital surgical department from January 2019 till May 2022 and were analyzed retrospectively. Patients were classified according to the ATOM classification. Management options undertaken were mentioned and compared to the timing of diagnosis, and the morbidity and mortality rates (using the Clavien-Dindo classification). RESULTS: 35 patients with BDI after both laparoscopic cholecystectomy (LC) (54.3%), and Open cholecystectomy (OC) (45.7%) (20% were converted and 25.7% were Open from the start) were classified according to ATOM classification. 45.7% were main bile duct injuries (MBDI), and 54.3% were non-main bile duct injuries (NMBDI), where only one case 2.9% was associated with vasculobiliary injury (VBI). 28% (n = 10) of the cases were diagnosed intraoperatively (Ei), 62.9% were diagnosed early postoperatively (Ep), and 8.6% were diagnosed in the late postoperative period (L). LC was associated with 84.2% of the NMBDI, and only 18.8% of the MBDI, compared to OC which was associated with 81.3% of the MBDI, and 15.8% of the NMBDI. By the Clavien-Dindo classification, 68.6% fell into Class IIIb, 20% into Class I, 5.7% into Class V (mortality rate), 2.9% into Class IIIa, and 2.9% into Class IV. The Clavien-Dindo classification and the patient's injury (type and time of detection) were compared to investigation and management options. CONCLUSION: Management options should be defined individually according to the mode of presentation, the timing of detection of injury, and the type of injury. Early detection and management are associated with lower morbidity and mortality. Diagnostic Laparoscopy was associated with lower morbidity and better outcomes. A proper Reporting checklist should be designed to help improve the identification of injury types.

Early Cholecystectomy in Patients with Sickle Cell Disease with Uncomplicated Cholelithiasis Is Associated with Better Outcomes.

BACKGROUND: Up to 85% of patients with sickle cell disease (SCD) will develop gallstones by their third decade. Cholecystectomy is the most commonly performed procedure in these patients. Cholecystectomy is recommended for patients with SCD with symptomatic cholelithiasis and leads to lower morbidity. No contemporary large studies have evaluated this recommendation or associated clinical outcomes. This study evaluates clinical outcomes after cholecystectomy in patients with SCD and cholelithiasis with specific advanced clinical presentations. STUDY DESIGN: The Nationwide Inpatient Sample was queried for patients with SCD and gallbladder disease between 2006 and 2015. Patients were divided into groups based on their disease presentation, including uncomplicated cholelithiasis, acute and chronic cholecystitis, and gallstone pancreatitis. Clinical outcomes associated with disease presentation were analyzed. Statistical analysis was performed using the Student's t -test, chi-square test, ANOVA, and logistic regression. RESULTS: There were 6,662 patients with SCD who presented with cholelithiasis. Median age was 20 (interquartile range 16 to 34) years and 54% were female patients. Cholecystectomy was performed in 1,779 patients with SCD with the most common indication being chronic cholecystitis (44%), followed by uncomplicated cholelithiasis (27%), acute cholecystitis (21%), and choledocholithiasis or gallstone pancreatitis (8%). On multivariable regression, advanced clinical presentation was the strongest predictor of perioperative vaso-occlusive crisis, which was the most common complication. Patients undergoing cholecystectomy for uncomplicated cholelithiasis were at lower risk than those with acute cholecystitis (odds ratio [OR] 2.37; 95% CI 1.64 to 3.41), chronic cholecystitis (OR 1.74; 95% CI 1.26 to 2.4), and choledocholithiasis or gallstone pancreatitis (OR 2.24; 95% CI 1.41 to 3.57). CONCLUSIONS: Seventy-three percent of patients with SCD have advanced clinical presentation at the time of their cholecystectomy. After cholecystectomy, perioperative vaso-occlusive events were significantly increased in patients with advanced clinical presentation. These data support screening abdominal ultrasounds and early cholecystectomy for cholelithiasis in patients with SCD.

Intrahepatic biloma after intraoperative cholangiography.

A woman in her 30s presented to the emergency department with a month-long history of postprandial epigastric pain radiating to her back. The diagnosis of cholecystolithiasis and suspected choledocholithiasis was made, and the patient underwent cholecystectomy with cholangiography using standard technique. The surgery was complicated by an intrahepatic bile duct injury attributed to high injection pressure during cholangiography. She developed an intrahepatic collection that was drained and confirmed the diagnosis of biloma. In this case report, we discuss a rare complication of intraoperative cholangiography during laparoscopic cholecystectomy and consider a way to prevent it.

Cholecystectomy and ERCP in pregnancy: a nationwide register-based study.

OBJECTIVE: The objective was to examine the outcomes of cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP) during pregnancy and compare these outcomes with those in nonpregnant women of fertile age. SUMMARY BACKGROUND DATA: Although both laparoscopic cholecystectomy and ERCP are considered safe and feasible in pregnant patients, there is still concern and uncertainty regarding gallstone intervention during pregnancy. This study aimed to investigate outcomes in pregnant patients compared to outcomes in nonpregnant patients. METHODS: Data on all female patients aged 18-45 years were retrieved from the Swedish Registry for Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography. The patients were divided into groups according to intervention: cholecystectomy, ERCP, or a combination thereof. Differences between pregnant and nonpregnant patients were analyzed. RESULTS: A total of 21 328 patients were included, with 291 cholecystectomy and 63 ERCP procedures performed in pregnant patients. At the 30-day follow-up, more complications after cholecystectomy were registered for pregnant patients. However, pregnancy was not a significant risk factor for adverse events when adjusting for previous complicated gallstone disease, intraoperative complications, emergency surgery, and common bile duct stones. There were no differences in outcomes when comparing cholecystectomy among the different trimesters. ERCP had no significant effect on outcomes at the 30-day follow-up. CONCLUSION: Cholecystectomy, ERCP, and combinations thereof are safe during pregnancy.

Evaluating Clinical Outcomes of Laparoscopic Subtotal and Total Cholecystectomy for Complicated Acute Cholecystitis: A Systematic Review and Meta-Analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to compare clinical outcomes in patients with complicated acute cholecystitis undergoing laparoscopic total vs subtotal cholecystectomy. METHODS: This systematic review and meta-analysis was conducted according to PRISMA guidelines and queried PubMed, Embase, ProQuest, Google Scholar, and Cochrane databases from inception to May 2023. The primary outcome was complication rates including common bile duct injury, wound infection, reoperation, bile leak, retained stones, and subhepatic collection, whereas secondary outcomes were in-hospital mortality and hospital length of stay. RESULTS: A total of 7 studies with 135,233 cases were included for meta-analysis. Patients who underwent laparoscopic total cholecystectomy had a significantly lower risk of postoperative bile leaks (RR: .15; 95% CI: .03, .80) and subhepatic fluid collection (RR: 0.19; 95% CI: .06, .63) and were 2.94 times less likely to die compared to those who underwent subtotal cholecystectomy (RR .34; 95% CI: .15, .77). Patients who underwent subtotal cholecystectomy had significantly longer hospital length of stay (mean difference 1.0 days; 95% CI: .5 days, 1.4 days). CONCLUSIONS: In adult patients presenting with complicated cholecystitis, management with laparoscopic subtotal cholecystectomy presents a unique complication profile with increased risk of postoperative bile leak and subhepatic fluid collection, in-hospital mortality, and longer hospital length-of-stay when used as an alternative approach to laparoscopic total cholecystectomy. Further research into the most appropriate clinical scenarios and patient populations for the use of the subtotal cholecystectomy approach may prove useful in improving its associated outcomes.

Transversus Abdominis Plane Block VS. Local Wound Infiltration for Elective Minimally Invasive Cholecystectomy in Children: A Prospective Randomized Trial.

BACKGROUND: The efficacy of transversus abdominis plane (TAP) block versus local anesthetic wound infiltration (LWI) in pediatric laparoscopic surgery is largely unknown. The objective of this study was to prospectively analyze this in minimally invasive cholecystectomy. We hypothesized that TAP block would be superior to LWI in terms of pain control and post-operative complications. METHODS: We conducted a prospective, randomized, single-blinded, controlled trial between 2017 and 2022 after obtaining Institutional Review Board (IRB) approval. After randomization, patients received a standard amount of ropivacaine via either 1) ultrasound-guided TAP block after general anesthesia induction or 2) local injection at port insertion by the operating surgeon. We collected data including operative time, pain scores, and medication usage post-operatively. We used descriptive statistics to report all endpoints and compared data with t-tests and Fisher's exact tests. A p-value less than 0.05 was considered statistically significant. RESULTS: We enrolled 85 patients (43 LWI, 42 TAP). Mean [standard deviation] age and body mass index (BMI) in the LWI and TAP groups were 14.8 [1.9] and 14.7 [2] years and 29.9 [7.2] and 27.4 [8.2] kilogram/meter2 (kg/m2) respectively. We did not find any significant differences in postoperative opioid use, pain scores, and gastrointestinal symptoms. TAP patients had significantly longer time between anesthesia-start and procedure-start (p < 0.001), although total time under anesthesia was not significantly different (p = 0.540). CONCLUSION: There are no significant differences between equal administration of local anesthetic by TAP block and surgeon administered LWI during minimally invasive cholecystectomy. TYPE OF STUDY: Randomized clinical trial. LEVEL OF EVIDENCE: Level II.

Extrahepatic abscess and dropped gallstones: a case report and a narrative review of an unusual delayed complication of laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy is the most common minimally invasive abdominal surgery procedure performed in Western countries; it offers several advantages over laparotomy but still carries some risks, such as intraoperative spillage of bile and gallstones. Diagnosis of dropped gallstones could be challenging, it is frequently delayed, and this can lead to further complications such as abscesses formation. METHODS: We report the history of a 51-year-old male with persistent dull abdominal pain in association to appetite loss, vomiting episodes and changes in regular bowel habits, a past medical history of laparoscopic cholecystectomy for biliary lithiasis (1.5 years earlier) and minimum elevation of inflammatory markers and gamma-GT values. RESULTS: Ultrasound examination showed perihepatic stones and magnetic resonance imaging revealed the presence of multiple perihepatic abscesses, findings compatible with fibrotic-inflammatory phenomena from 'dropped gallstones'. A re-laparoscopy was then performed with an abscess collection containing multiple gallstones; a liver wedge resection was also required due to strong adhesions. At follow up, the patient had improved both on clinical and biochemical perspective. CONCLUSION: Dropped gallstones are an underreported cause of morbidity and diagnostic dilemmas in subjects who underwent to laparoscopic cholecystectomy, in relation to infectious complications that can occur even several months or years after surgery. Imaging represents a valuable aid in the correct non-invasive diagnostic process, but proper awareness of this insidious condition is necessary. Surgeons and radiologists should always consider this eventuality in the differential diagnosis of a patient presenting with abdominal abscesses and history of cholecystectomy.

Simplified risk stratification in early cholecystectomy for acute cholecystitis based on age: A report from an institution with zero mortality.

BACKGROUND/PURPOSE: The existing risk stratification for early cholecystectomy in patients with acute cholecystitis (AC) is complex. This study aims to establish a simpler risk assessment for surgical complications after cholecystectomy based on age group. METHODS: This single-center retrospective observational study enrolled 350 patients diagnosed with AC who underwent early cholecystectomy within 72 h of diagnosis from 2013 to 2021. Patients were divided into three subgroups based on age: young (<65 years), elderly (65-79 years), and very elderly (≥80 years). Since no mortality was observed, risk factors for the Clavien-Dindo (CD) grade ≥ II complications were identified within the entire cohort and in each subgroup. RESULTS: There were 120 young, 130 elderly, and 100 very elderly patients. The overall prevalence of complications with CD grade ≥ II was 11.1%. Age and Tokyo Guidelines 18 (TG18) severity were independent risk factors for surgical complications in the whole cohort. Subgroup analysis revealed that there was no independent risk factor in the young group. Meanwhile, age and poor physical status were independent risk factors in the elderly group, and TG18 severity in the very elderly group. CONCLUSION: Evaluation of only age, physical status, and TG18 severity may be sufficient for risk stratification of surgical complications of AC.

Meta-analysis of fenestrating versus reconstituting subtotal cholecystectomy in the management of difficult gallbladder.

AIMS: To evaluate comparative outcomes of fenestrating and reconstituting subtotal cholecystectomy (STC) in patients with difficult gallbladder. METHODS: A systematic search of electronic data sources and bibliographic reference lists were conducted. All comparative studies reporting outcomes of laparoscopic fenestrating and reconstituting STC were included and their risk of bias were assessed using ROBINS-I tool. RESULTS: Seven comparative studies were included enrolling 590 patients undergoing laparoscopic STC using either fenestrating (n = 353) or reconstituting (n = 237) approaches. Although fenestrating STC was associated with a significantly higher rate of bile leak (OR: 2.47, p = 0.007) compared to reconstituting STC, both approaches were comparable in terms of resolution of bile leak without (RD: -0.02, p = 0.86) or with (OR: 1.84, p = 0.40) postoperative ERCP. Moreover, there was no significant difference in development of bile duct injury (RD: -0.02, p = 0.16), need for postoperative ERCP (OR: 1.36, p = 0.49), wound infection (RD: 0.03, p = 0.27), re-operation (OR: 0.95, p = 0.95), gallbladder remnant cholecystitis (OR: 0.21, p = 0.09) or need for completion cholecystectomy (RD: 0.01, p = 0.59) between two groups. CONCLUSIONS: Fenestrating STC is associated with a higher risk of bile leak than the reconstructing technique. This issue can be mitigated by routine use of drains, delayed drain removal, and in selected cases endoscopic therapy. We encourage the fenestrating approach considering trends in improved short- and long-term outcomes.