Before and after COVID-19 pandemic: impact on hepatobiliary and pancreatic surgical services in a Singapore Tertiary Hospital.

BACKGROUND: Reallocation of healthcare resources to prioritize the COVID-19 pandemic-related incremental healthcare needs resulted in longer waiting times for routine elective clinical services. AIMS: We aimed to analyze the effects of the pandemic on the hepatopancreatobiliary (HPB) unit's surgical workload. METHODS: The HPB unit's surgical workload for the months of January-June from 2019 to 2022 was extracted, retrospectively compared, and analyzed. This study was registered in ClinicalTrials.gov (NCT05572866) and complies with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. RESULTS: Benign elective surgeries were impacted adversely, with elective gallbladder operations decreasing by 45.2% (146 in 2019 vs 80 in 2020, p = 0.89) before slowly increasing to 120 cases in 2021 and rebounding to 179 cases in 2022 (p = 0.001). Elective oncology operations paradoxically increased, with liver resections rising by 12.9% (31 in 2019 vs 35 in 2020, p = 0.002) and maintaining 37 cases in 2021 (p = 0.0337) and 34 cases in 2022 (p = 0.69). Elective pancreatic resections increased by 171.4% (7 in 2019 vs 19 in 2020, p < 0.0001) and were maintained at 15 cases in 2021 (p = 0.013) and 18 cases in 2022 (p = 0.022). The overall emergency workload decreased from 2019 (n = 198) to 2020 (n = 129) to 2021 (n = 122) before recovering to baseline in 2022 (n = 184). The month-on-month volume generally showed similar trends compared to the other years except for February 2022 and May 2021. CONCLUSION: This audit shows that despite large-scale disruption of the local healthcare system, essential surgeries can still proceed with careful resource planning by steadfast and vigilant clinical teams.

Are outcomes for emergency index-admission laparoscopic cholecystectomy performed by hepatopancreatobiliary surgeons better compared to non-hepatopancreatobiliary surgeons? A 10-year audit using 1:1 propensity score matching.

BACKGROUND: Emergency index-admission cholecystectomy (EIC) is recommended for acute cholecystitis in most cases. General surgeons have less exposure in managing "difficult" cholecystectomies. This study aimed to compare the outcomes of EIC between hepatopancreatobiliary (HPB) versus non-HPB surgeons. METHODS: This is a 10-year retrospective audit on patients who underwent EIC from December 2011 to March 2022. Patients who underwent open cholecystectomy, had previous cholecystitis, previous endoscopic retrograde cholangiopancreatography or cholecystostomy were excluded. A 1:1 propensity score matching (PSM) was performed to adjust for confounding variables (e.g. age ≥ 75 years, history of abdominal surgery, presence of dense adhesions). RESULTS: There were 1409 patients (684 HPB cases, 725 non-HPB cases) in the unmatched cohort. Majority (52.3%) of them were males with a mean age of 59.2 ± 14.9 years. Among 472 (33.5%) patients with EIC performed ≥ 72 hours after presentation, 40.1% had dense adhesion. The incidence of any morbidity, open conversion, subtotal cholecystectomy and bile duct injury were 12.4%, 5.0%, 14.6% and 0.1%, respectively. There was one mortality within 30 days from EIC. PSM resulted in 1166 patients (583 per group). Operative time was shorter when EIC was performed by HPB surgeons (115.5 min vs. 133.4 min, P < 0.001). The mean length of hospital stay was comparable. EIC performed by HPB surgeons was independently associated with lower open conversion [odds ratio (OR)=  0.24, 95% confidence interval (CI): 0.12-0.49, P < 0.001], lower fundus-first cholecystectomy (OR=  0.58, 95% CI: 0.35-0.95, P=  0.032), but higher subtotal cholecystectomy (OR=  4.19, 95% CI: 2.24-7.84, P < 0.001). Any morbidity, bile duct injury and mortality were comparable between the two groups. CONCLUSION: EIC performed by HPB surgeons were associated with shorter operative time and reduced risk of open conversion. However, the incidence of subtotal cholecystectomy was higher.

Learning Curve of Laparoscopic Common Bile Duct Exploration: A Systematic Review.

Background: Single-stage laparoscopic common bile duct exploration (LCBDE) with cholecystectomy has superior outcomes over two-stage endoscopic retrograde cholangiopancreatogram with interval cholecystectomy. With decreasing trend of LCBDE, this study aims to summarize the literature on learning curve (LC) in LCBDE. Materials and Methods: PubMed, Embase, Scopus, and the Cochrane Library were systematically searched for articles from inception to June 3, 2022 (PROSPERO Ref No: CRD42022328451). Basic clinical demographics were collected. Poisson means (95% confidence interval [95% CI]) was used to determine the number of cases required to surmount the LC (NLC). Results: Eight articles (n = 2071 patients) reported LC outcomes in LCBDE with mean study period of 5.9 ± 2.8 years. Majority of studies (62.5%) used arbitrary methods of LC analysis. Most common outcomes reported were complications (any or major) (75%), open conversion (75%), length of stay (62.5%), and operating time (50%). Mean CBD diameter was 11.3 ± 4.8 mm (n = 1122 patients). Incidence of acute cholecystitis, acute cholangitis, and acute pancreatitis were 13.9% (n = 232/1668), 7.8% (n = 128/1629), and 13.7% (n = 229/1668), respectively. Pooled analysis of all the included studies showed NLC of 78.8 cases (95% CI: 71.9-86.3). Studies that used cumulative sum control chart analysis, nonarbitrary methods, and arbitrary-based LC had NLC of 152.0 (95% CI: 135.4-170.1), 108.0 (95% CI: 96.6-120.4), and 49.7 (95% CI: 42.0-58.3) cases, respectively. NLC was 37.0 cases (95% CI: 29.1-46.5) for single surgeon LC, and 99.8 cases (95% CI: 90.2-110.0) for institutional LC. Conclusion: Studies reporting NLC in LCBDE are heterogeneous. Further studies should use nonarbitrary methods of analysis for patient-reported outcome measures and procedure-specific morbidity.

Aging is Associated with Prolonged Hospitalisation Stay in Pyogenic Liver Abscess-A 1:1 Propensity Score Matched Study in Elderly Versus Non-Elderly Patients.

Background: Mortality of pyogenic liver abscess (PLA) is high ranging 10%-40%. Old age predicts outcomes in many diseases but there is paucity of data on PLA outcomes. We aim to compare the morbidity and mortality between elderly and non-elderly in PLA. Methods: This is a retrospective study from 2007-2011 comparing elderly (≥ 65 years old) and non-elderly (< 65 years old) with PLA. A 1:1 propensity score matching (PSM) was performed. Baseline clinical profile and outcomes were compared. Results: There were 213 patients (elderly patients = 90 [42.3%], non-elderly patients = 123 [57.7%]). Overall median age is 62 (interquartile range [IQR] = 53-74) years old. PSM resulted in 102 patients (51 per arm). Length of hospitalisation stay (LOS) was significantly longer in elderly patients in both unmatched (16 [IQR = 10-24.5] versus 11 [IQR = 8-19] days; P < 0.001) and matched cohorts (17 [IQR = 13-27] versus 11 [IQR = 7-19] days; P = 0.001). In-hospital mortality was significantly higher in elderly patients in the unmatched cohort (elderly patients = 21.1%, non-elderly patients = 7.3%; P = 0.003) but was insignificant following PSM (elderly patients = 15.7%, non-elderly patients = 9.8%; P = 0.219). Duration of antibiotic therapy and need for percutaneous drainage (PD) were comparable before and after PSM. Conclusion: Age ≥ 65 years old is associated with longer LOS. In-hospital mortality though higher in elderly patients, was not statistically significant.

Outcomes of surgical resection of super-giant (≥15 cm) hepatocellular carcinoma: Volume does matter, if not the size.

Background and Aim: Resection for giant hepatocellular carcinoma (HCC) (≥10 cm) is deemed safe and feasible. However, a super-giant HCC (≥15 cm) poses unique technical complexity for hepatectomy with limited data suggesting feasibility and oncologic efficiency. This study aims to evaluate the short-term and long-term outcomes of hepatectomy in patients with super-giant HCC. Methods: A retrospective review was conducted on patients with super-giant HCC who underwent hepatectomy from 2011 to 2021. We report perioperative and oncologic outcomes such as length of stay (LOS), 30-day readmission, 90-day mortality, and cumulative survival rate. Results: Of the 18 patients, the median tumor diameter was 172.5 mm (range 150-250). The most common risk factor was chronic hepatitis B virus (HBV) infection (n=7, 38.9%). Most of the patients were Barcelona Clinic Liver Cancer (BCLC) Stage B (n=14, 77.8%) and Hong Kong Liver Cancer (HKLC) Stage IIb (n=15, 83.3%). Extended right hepatectomy was the most common procedure. The median LOS was 11 days (range 3-90). The most common post-operative complication was pneumonia (n=4, 22.2%). Fourteen patients were discharged well without any need for invasive therapy (n=7, 38.9% no complications, n=1, 5.6% Clavien Grade I, n=6, 33.3% Clavien Grade II). Thirty-day readmission rate was 5.6% (n=1) and 90-day mortality rate was 5.6% (n=1). There were 12 patients (66.7%) with microvascular invasion and three patients (16.7%) with macrovascular invasion. Most patients had Grade III (poorly differentiated) HCC (n=9, 50%). At a median follow-up of 11 months (range 2-95), 12 (66.7%) patients had local recurrence, and 9 (50%) developed distant metastasis. The 1-, 2-, and 3-year cumulative disease-free survival (DFS) was 36%, 18%, and 18%, respectively. The 1-, 2-, and 3-year cumulative overall survival was 49% and 39%, and 29%, respectively. Conclusion: Primary hepatic resection is safe in patients with super-giant HCC. However, long-term outcomes are poor, and high tumor volume may be associated with inferior oncological outcomes in HCC. Relevance for Patients: The presentation of super-giant HCCs may be asymptomatic and some patients are diagnosed late with limited treatment options. In some centers, this group of patients are denied surgical resection and recommended for only locoregional therapies like TACE. This paper demonstrates that hepatic resection is safe and may be an option in patients who present at an advanced stage with a high tumor burden.

Contralateral Acute Extradural Hematoma Following Decompressive Craniectomy for Subdural Hematoma Evacuation: A Rare Complication and a Short Literature Review.

Subdural hematoma (SDH) is a common intracranial lesion seen in severe traumatic brain injury (TBI). The development of contralateral delayed extradural hematoma (EDH) after surgery is well described. But limited literature available about immediate contralateral EDH after subdural hematoma (SDH) evacuation. We report a case of a young adult who developed contralateral EDH following decompressive surgery for acute SDH.

Dapagliflozin protects neural and vascular dysfunction of the retina in diabetes.

INTRODUCTION: Dapagliflozin, a sodium-glucose transporter inhibitor, effectively reduces blood glucose and is indicated for individuals with kidney diseases and cardiovascular disorders. In this study, we further expand the therapeutic benefit of dapagliflozin in the neural and vascular retina, with the potential to effectively manage diabetic retinopathy (DR), the most common complication of diabetes. RESEARCH DESIGN AND METHODS: Db/db mice, an animal model of type 2 diabetes, were treated with dapagliflozin orally, and the electroretinogram (ERG) response and acellular capillary numbers were assessed. Messenger RNA levels of inflammatory cytokines were studied using real-time quantitative (q)PCR. We assessed endothelial cell migration in a scratch wound assay and retinal glucose uptake using human retinal endothelial cells. RESULTS: The dapagliflozin treatment improved the ERG b-wave amplitude and decreased acellular capillary numbers. The scratch wound assay demonstrated a reduction in wound closure after dapagliflozin treatment. Retinal glucose uptake reduced after dapagliflozin treatment compared with the respective controls. CONCLUSIONS: Our studies suggest that dapagliflozin treatment effectively corrects neural and vascular dysfunction of the retina in diabetes. This effect is mediated by a decrease in inflammation and improved glycemic control. In addition, dapagliflozin exhibits decreased wound healing and glucose uptake, which could benefit the retina. Thus, dapagliflozin could be helpful in the management of DR, with multimodal therapeutic effects.

On-table hepatopancreatobiliary surgical consults for difficult cholecystectomies: A 7-year audit.

BACKGROUND: Cholecystectomy is considered a general surgical operation. However, general surgeons are not trained to manage severe complications such as bile duct injury (BDI) and should refer to hepatopancreatobiliary (HPB) surgeons when difficulty arises. This study aimed to investigate the outcomes of patients who had on-table HPB consults during cholecystectomy. METHODS: This is an audit of 50 patients who required on-table HPB consult during cholecystectomy from 2011 to 2017. Consultations were classified as "proactive" and "reactive", where consults were made before or after surgical incision, respectively. Patient demographics and perioperative details were collected. RESULTS: The median age of the patients was 62.5 years [interquartile range (IQR) 50.8-71.3 years]. Eight (16%) patients had underlying HPB co-morbidity. Gallbladder wall was thickened in all patients (median 5 mm, IQR 4-7 mm), and common bile duct was of normal caliber in all patients (median 5 mm, IQR 4-6 mm). Median length of operation and length of stay were 165 min (IQR 124-209 min) and five days (IQR 3-7 days), respectively. Subtotal cholecystectomy was performed in 18 (36%) patients. Forty-eight patients were initially managed by laparoscopic approach, 15 (31%) required open conversion; majority (9/15, 60%) were initiated before on-table consult. Majority of referrals (98%) were reactive. Common reasons for referral included unclear anatomy or anatomical variations (30%), presence of dense adhesions and/or contracted gallbladder (18%) and impacted stones in Hartmann's pouch (16%). Three (6%) patients were referred for BDI (2 Strasberg D and 1 Strasberg E1), and two (4%) were referred for torrential bleeding from arterial injury (1 cystic artery and 1 right hepatic artery). Any morbidity and 30-day readmission were 22% and 6%, respectively. There was no 90-day mortality. CONCLUSIONS: Calling for help in BDI is obligatory, but in other instances is a personal choice. Calling for help prior to open conversion is lacking and this awareness should be raised. Whether surgical outcomes could be improved by early HPB consult needs to be determined by larger multicenter reports.

Predictors of mortality within the first year post-hepatectomy for hepatocellular carcinoma.

BACKGROUND: Hepatic resection (HR) for hepatocellular carcinoma (HCC) is safe with good perioperative and long-term oncologic outcomes. There is a paucity of data with regards to intermediate-term outcomes (i.e., beyond 90-day and within 1-year mortality). This paper studies the risk factors for within 1-year mortality after elective HR with curative intent in patients with HCC. METHODS: An audit of patients who underwent curative HR for HCC from January 2007 to April 2016 was conducted. Univariate and multivariate analysis were sequentially performed on perioperative variables using Cox-regression analysis to identify factors predicting intermediate-term outcomes defined as within 1-year mortality. Kaplan-Meier survival curves and hazard ratios were obtained. RESULTS: Three hundred forty-eight patients underwent HR during the study period and 163 patients had curative hepatectomy for HCC. Fifteen patients (9.2%) died within 1-year after HR. Multivariate analysis identified Child-Pugh class B/C (HR 5.5, p = 0.035), multinodularity (HR 7.1, p = 0.001), macrovascular invasion (HR 4.2, p = 0.04) postoperative acute renal failure (HR 5.8, p = 0.049) and posthepatic liver failure (HR 9.6, p = 0.009) as significant predictors of 1-year mortality. CONCLUSION: One-year mortality following HR for HCC remains high and can be predicted preoperatively by multinodularity, Child-Pugh class, and macrovascular invasion. Postoperative acute renal failure and liver failure are associated with 1-year mortality.

Mucormycosis in COVID-19 patients: The patient profile, contributing factors and postoperative outcome - A case series of 14 patients.

Co-infection of coronavirus disease 2019 (COVID-19) patients with life-threatening mucormycosis was seen as a major health crisis during the recent surge of coronavirus disease cases. We have taken 14 affected patients who were operated on at our centre and noted associated risk factors, intraoperative courses and surgical outcome in immediate peri-operative course. Out of 14 patients, 8 were people with diabetes while 2 were freshly detected/had corticosteroid-induced hyperglycaemia. Although our sample size is small, it is evident that patients who had diabetes, who were treated with steroids and who received supplemental oxygen support are more prone to contract mucormycosis infection. Also, patients who have the more severe form of COVID-19 pneumonia and those who need to be operated on early (within 20 days of COVID-19 infection) are likely to have turbulent intraoperative and postoperative courses. Therefore, optimization before surgery is of paramount importance.

Sequential organ failure assessment score is superior to other prognostic indices in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a common surgical condition, with severe AP (SAP) potentially lethal. Many prognostic indices, including; acute physiology and chronic health evaluation II score (APACHE II), bedside index of severity in acute pancreatitis (BISAP), Glasgow score, harmless acute pancreatitis score (HAPS), Ranson's score, and sequential organ failure assessment (SOFA) evaluate AP severity and predict mortality. AIM: To evaluate these indices' utility in predicting severity, intensive care unit (ICU) admission, and mortality. METHODS: A retrospective analysis of 653 patients with AP from July 2009 to September 2016 was performed. The demographic, clinical profile, and patient outcomes were collected. SAP was defined as per the revised Atlanta classification. Values for APACHE II score, BISAP, HAPS, and SOFA within 24 h of admission were retrospectively obtained based on laboratory results and patient evaluation recorded on a secure hospital-based online electronic platform. Data with < 10% missing data was imputed via mean substitution. Other patient information such as demographics, disease etiology, and patient outcomes were also derived from electronic medical records. RESULTS: The mean age was 58.7 ± 17.5 years, with 58.7% males. Gallstones (n = 404, 61.9%), alcohol (n = 38, 5.8%), and hypertriglyceridemia (n = 19, 2.9%) were more common aetiologies. 81 (12.4%) patients developed SAP, 20 (3.1%) required ICU admission, and 12 (1.8%) deaths were attributed to SAP. Ranson's score and APACHE-II demonstrated the highest sensitivity in predicting SAP (92.6%, 80.2% respectively), ICU admission (100%), and mortality (100%). While SOFA and BISAP demonstrated lowest sensitivity in predicting SAP (13.6%, 24.7% respectively), ICU admission (40.0%, 25.0% respectively) and mortality (50.0%, 25.5% respectively). However, SOFA demonstrated the highest specificity in predicting SAP (99.7%), ICU admission (99.2%), and mortality (98.9%). SOFA demonstrated the highest positive predictive value, positive likelihood ratio, diagnostic odds ratio, and overall accuracy in predicting SAP, ICU admission, and mortality. SOFA and Ranson's score demonstrated the highest area under receiver-operator curves at 48 h in predicting SAP (0.966, 0.857 respectively), ICU admission (0.943, 0.946 respectively), and mortality (0.968, 0.917 respectively). CONCLUSION: The SOFA and 48-h Ranson's scores accurately predict severity, ICU admission, and mortality in AP, with more favorable statistics for the SOFA score.

Diverse, Potent, and Efficacious Inhibitors That Target the EED Subunit of the Polycomb Repressive Complex 2 Methyltransferase.

Aberrant activity of the histone methyltransferase polycomb repressive complex 2 (PRC2) has been linked to several cancers, with small-molecule inhibitors of the catalytic subunit of the PRC2 enhancer of zeste homologue 2 (EZH2) being recently approved for the treatment of epithelioid sarcoma (ES) and follicular lymphoma (FL). Compounds binding to the EED subunit of PRC2 have recently emerged as allosteric inhibitors of PRC2 methyltransferase activity. In contrast to orthosteric inhibitors that target EZH2, small molecules that bind to EED retain their efficacy in EZH2 inhibitor-resistant cell lines. In this paper we disclose the discovery of potent and orally bioavailable EED ligands with good solubilities. The solubility of the EED ligands was optimized through a variety of design tactics, with the resulting compounds exhibiting in vivo efficacy in EZH2-driven tumors.

Validation of Tokyo Guidelines 2007 and Tokyo Guidelines 2013/2018 Criteria for Acute Cholangitis and Predictors of In-Hospital Mortality.

BACKGROUND: Acute cholangitis (AC) is a common emergency with a significant mortality risk. The Tokyo Guidelines (TG) provide recommendations for diagnosis, severity stratification, and management of AC. However, validation of the TG remains poor. This study aims to validate TG07, TG13, and TG18 criteria and identify predictors of in-hospital mortality in patients with AC. METHODS: This is a retrospective audit of patients with a discharge diagnosis of AC in the year 2016. Demographic, clinical, investigation, management and mortality data were documented. We performed a multinomial logistic regression analysis with stepwise variable selection to identify severity predictors for in-hospital mortality. RESULTS: Two hundred sixty-two patients with a median age of 75.9 years (IQR 64.8-82.8) years were included for analysis. TG13/TG18 diagnostic criteria were more sensitive than TG07 diagnostic criteria (85.1 vs. 75.2%; p < 0.006). The majority of the patients (n = 178; 67.9%) presented with abdominal pain, pyrexia (n = 156; 59.5%), and vomiting (n = 123; 46.9%). Blood cultures were positive in 95 (36.3%) patients, and 79 (83.2%) patients had monomicrobial growth. The 30-day, 90-day, and in-hospital mortality numbers were 3 (1.1%), 11 (4.2%), and 15 (5.7%), respectively. In multivariate analysis, type 2 diabetes mellitus (OR = 12.531; 95% CI 0.354-116.015; p = 0.026), systolic blood pressure <100 mm Hg (OR = 10.108; 95% CI 1.094-93.395; p = 0.041), Glasgow coma score <15 (OR = 38.16; 95% CI 1.804-807.191; p = 0.019), and malignancy (OR = 14.135; 95% CI 1.017-196.394; p = 0.049) predicted in-hospital mortality. CONCLUSION: TG13/18 diagnostic criteria are more sensitive than TG07 diagnostic criteria. Type 2 diabetes mellitus, systolic blood pressure <100 mm Hg, Glasgow coma score <15, and malignant etiology predict in-hospital mortality in patients with AC. These predictors could be considered in acute stratification and treatment of patients with AC.

3D Laparoscopic common bile duct exploration with primary repair by absorbable barbed suture is safe and feasible.

BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP), with interval laparoscopic cholecystectomy (LC), is the most common treatment approach for common bile duct (CBD) stones. However, recent studies show that single-stage laparoscopic CBD exploration (LCBDE) is safe and feasible. Three-dimensional (3D) laparoscopy enhances depth perception and facilitates intracorporeal suturing. The application of 3D technology for LCBDE is emerging, and we report our case series of 3D LCBDE. METHODS: We audited the 27 consecutive 3D LCBDE performed from July 2017 to January 2020. We have a liberal policy for magnetic resonance cholangiopancreatography (MRCP) in patients with deranged liver function tests (LFT). All CBD explorations were done through choledochotomy with a 5 mm flexible choledochoscope and primarily repaired with an absorbable barbed suture without a stent or T-tube. RESULTS: The mean age of patients was 68 (range 44-91) years, and 12 (44%) were male. The indications for surgery were choledocholithiasis 67% (n=18), cholangitis 22% (n=6), and gallstone pancreatitis 11% (n=3). About 67% (n=18) had pre-operative ERCP. About 37% (n=10) had pre-operative biliary stent. Pre-operative MRCP was done in 74% (n=20), and the mean diameter of CBD was 14.5 mm (range 7-30). The median operative time was 160 (range 80-265) min. The operative drain was inserted in 18 patients. One patient each (4%) had a bile leak and a retained stone. There was no open conversion, readmission, or mortality. CONCLUSION: 3D LCBDE with primary repair by an absorbable barbed suture is safe and feasible. RELEVANCE FOR PATIENTS: This paper emphasized that one stage LCBDE should be a treatment option which is comparable with two stage ERCP followed by LC to treat CBD stones. In addition, 3D technology and barbed sutures use in LCBDE are safe and useful.

A study of 3013 cases of hepatocellular carcinoma: Etiology and therapy before and during the current decade.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a significant global problem. With advances in HCC diagnosis and therapy, our hypothesis is that there are significant differences in the clinical characteristics and treatment of HCC over the years. METHODS: Patients with HCC between 1980 and 2018 from three major tertiary hospitals in Singapore were enrolled into a Research Electronic Data Capture database. Clinical characteristics and treatment of HCC were compared between those diagnosed before 2008 (cohort A) and during the current decade (ie from 2008 onwards) (cohort B). RESULTS: There were 3013 patients. Mean age of HCC diagnosis was significantly older in cohort B (68.6 vs 61.2 years, P < 0.001). The most common etiology remained as chronic hepatitis B infection but the proportion due to hepatitis B was significantly lower in cohort B (46.6% vs 57.2%, P < 0.0001). The prevalence of cryptogenic/non-alcoholic steatohepatitis was significantly higher in cohort B than cohort A (27.1% vs 18.6%, P < 0.0001). More patients received curative therapy in cohort B (43.7% vs 27.1%, P < 0.0001. CONCLUSION: In this largest collection of HCC patients in Singapore, patients are diagnosed with HCC at an older age and cryptogenic/non-alcoholic steatohepatitis is becoming more important as an etiology of HCC in the current decade. More patients also received curative therapy in the current decade.

Sustaining a Multidisciplinary, Single-Institution, Postoperative Mobilization Clinical Practice Improvement Program Following Hepatopancreatobiliary Surgery During the COVID-19 Pandemic: Prospective Cohort Study.

BACKGROUND: The Enhanced Recovery After Surgery (ERAS) protocol has been recently extended to hepatopancreatobiliary (HPB) surgery, with excellent outcomes reported. Early mobilization is an essential facet of the ERAS protocol, but compliance has been reported to be poor. We recently reported our success in a 6-month clinical practice improvement program (CPIP) for early postoperative mobilization. During the COVID-19 pandemic, we experienced reduced staffing and resource availability, which can make CPIP sustainability difficult. OBJECTIVE: We report outcomes at 1 year following the implementation of our CPIP to improve postoperative mobilization in patients undergoing major HPB surgery during the COVID-19 pandemic. METHODS: We divided our study into 4 phases-phase 1: before CPIP implementation (January to April 2019); phase 2: CPIP implementation (May to September 2019); phase 3: post-CPIP implementation but prior to the COVID-19 pandemic (October 2019 to March 2020); and phase 4: post-CPIP implementation and during the pandemic (April 2020 to September 2020). Major HPB surgery was defined as any surgery on the liver, pancreas, and biliary system with a duration of >2 hours and with an anticipated blood loss of ≥500 ml. Study variables included length of hospital stay, distance ambulated on postoperative day (POD) 2, morbidity, balance measures (incidence of fall and accidental dislodgement of drains), and reasons for failure to achieve targets. Successful mobilization was defined as the ability to sit out of bed for >6 hours on POD 1 and ambulate ≥30 m on POD 2. The target mobilization rate was ≥75%. RESULTS: A total of 114 patients underwent major HPB surgery from phases 2 to 4 of our study, with 33 (29.0%), 45 (39.5%), and 36 (31.6%) patients in phases 2, 3, and 4, respectively. No baseline patient demographic data were collected for phase 1 (pre-CPIP implementation). The majority of the patients were male (n=79, 69.3%) and underwent hepatic surgery (n=92, 80.7%). A total of 76 (66.7%) patients underwent ON-Q PainBuster insertion intraoperatively. The median mobilization rate was 22% for phase 1, 78% for phases 2 and 3 combined, and 79% for phase 4. The mean pain score was 2.7 (SD 1.0) on POD 1 and 1.8 (SD 1.5) on POD 2. The median length of hospitalization was 6 days (IQR 5-11.8). There were no falls or accidental dislodgement of drains. Six patients (5.3%) had pneumonia, and 21 (18.4%) patients failed to ambulate ≥30 m on POD 2 from phases 2 to 4. The most common reason for failure to achieve the ambulation target was pain (6/21, 28.6%) and lethargy or giddiness (5/21, 23.8%). CONCLUSIONS: This follow-up study demonstrates the sustainability of our CPIP in improving early postoperative mobilization rates following major HPB surgery 1 year after implementation, even during the COVID-19 pandemic. Further large-scale, multi-institutional prospective studies should be conducted to assess compliance and determine its sustainability.

Diabetic Retinopathy in the Aging Population: A Perspective of Pathogenesis and Treatment.

The elderly population in the United States is projected to almost double by the year 2050. In addition, the numbers of diabetics are rising, along with its most common complication, diabetic retinopathy (DR). To effectively treat DR within the elderly population, it is essential first to consider the retinal changes that occur due to aging, such as decreased blood flow, retinal thinning, and microglial changes, and understand that these changes can render the retina more vulnerable to oxidative and ischemic damage. Given these considerations, as well as the pathogenesis of DR, specific pathways could play a heightened role in DR progression in elderly patients, such as the polyol pathway and the vascular endothelial growth factor (VEGF) axis. Current ocular treatments include intravitreal corticosteroids, intravitreal anti-VEGF agents, laser photocoagulation and surgical interventions, in addition to better control of underlying diabetes with an expanding range of systemic treatments. While using therapeutics, it is also essential to consider how pharmacokinetics and pharmacodynamics change with aging; oral drug absorption can decrease, and ocular drug metabolism might affect the dosing and delivery methods. Also, elderly patients may more likely be nonadherent to their medication regimen or appointments than younger patients, and undertreatment with anti-VEGF drugs often leads to suboptimal outcomes. With a rising number of elderly DR patients, understanding how aging affects disease progression, pharmacological metabolism, and adherence are crucial to ensuring that this population receives adequate care.