Timing of readmissions for complications following emergency colectomy: follow-up beyond post-operative day 30 matters.

BACKGROUND AND PURPOSE: Emergency colectomies are associated with a higher risk of complications compared to elective ones. A critical assessment of complications occurring beyond post-operative day 30 (POD30) is lacking. This study aimed to assess the readmission rate and factors associated with readmission 6-months following emergency colectomy. METHODS: A retrospective cohort study of adult patients who underwent emergency colectomy (2010-2018) was performed using the Nationwide Readmissions Database. The cohort was divided into two groups: (i) no readmission and (ii) emergency readmission(s) for complications related to colectomy (defined using ICD-9/10 codes). Readmissions were categorized as either "early" (POD0-30) or "late" (> POD30). Differences between groups were described and multivariable regression controlling for relevant covariates defined a priori were used to identify factors associated with timing of readmission and cost. RESULTS: Of 141,481 eligible cases, 13.22% (n = 18,699) were readmitted within 6-months of emergency colectomy for colectomy-related complications, 61.63% of which were "late" readmissions (> POD30). The most common reasons for "late" readmission were for bleeding, gastrointestinal, and infectious complications (20.80%, 25.30%, and 32.75%, respectively). On multiple logistic regression, female gender (OR 1.12; 95%CI 1.04-1.21), open procedures (OR 1.12, 95%CI 1.011-1.24), and sigmoidectomies (OR 1.51, 95%CI 1.39-1.65, relative to right hemicolectomies) were the strongest predictors of "late" readmission. On multiple linear regression, "late" readmissions were associated with a $1717.09 USD (95%CI $1717.05-$1717.12) increased cost compared to "early" readmissions. DISCUSSION: The majority of colectomy-related readmissions following emergency colectomy occur beyond POD30 and are associated with cases that are of overall higher morbidity, as well as open sigmoidectomies. Given the associated increased cost of care, mitigation of such readmissions by close follow-up prior to and beyond POD30 is advisable.

Extended versus limited mesenteric excision for operative Crohn's disease: 30-Day outcomes from the ACS-NSQIP database.

PURPOSE: Recent studies have suggested that extended mesenteric excision (ME) may reduce surgical reintervention in Crohn's Disease (CD), but there remains clinical concerns regarding potential peri-operative morbidity. This retrospective study compares 30-day perioperative morbidity between limited and extended ME in segmental colectomies for CD. METHODS: Using the American College of Surgeons National Surgical Quality Improvement (ACS-NSQIP) colectomy-specific database, all patients with CD undergoing segmental colectomy for non-malignant indications between 2014-2019 were included. A lymph node harvest of 12 or more nodes was used as a surrogate for extended ME. The primary outcome was NSQIP major morbidity. Secondary outcomes included abdominal complications and perioperative bleeding. RESULTS: Of 3,709 patients included from the ACS-NSQIP database, 3,087 underwent limited ME and 622 underwent extended ME. On univariate analysis, those with limited mesenteric excision were less likely to be anemic (46.1% vs 55.0%, p < 0.001) and have undergone an open surgery (44.7% vs 34.7%, p < 0.001). On univariate comparison of limited and extended ME, there was no significant difference in major morbidity. On multiple logistic regression, controlling for age, sex, BMI, smoking, preoperative sepsis, preoperative anemia, surgical approach, emergency surgery, stoma creation, bowel preparation, and immunosuppression, the extent of ME was not an independent predictor of NSQIP major morbidity (OR 1.1, 95% CI 0.84-1.44). Likewise, the extent of ME was not associated with an increase in abdominal complications (OR 0.95, 95% CI 0.76-1.19) or post-operative bleeding (OR 1.89, 95% CI 0.75-1.53). CONCLUSION: Extended ME for CD was not associated with an increase in 30-day perioperative major morbidity.

Is the Hartmann's procedure for diverticulitis obsolete? National trends in colectomy for diverticulitis in the emergency setting from 1993 to 2018.

BACKGROUND: Historically, Hartmann's procedure (HP) has been the operation of choice for diverticulitis in the emergency setting. However, recent evidence has demonstrated the safety of primary anastomosis (PA) with or without diverting ileostomy. The purpose of this study was to evaluate the trends of, and factors associated with, HP compared to PA in emergency surgery for diverticulitis over 25 years. METHODS: Using the National Inpatient Sample database, we identified adult patients ≥ 18 years old who underwent emergency surgery for diverticulitis (HP or PA) between 1993 and 2018 using ICD-9 and ICD-10 codes. Patients with inflammatory bowel disease, gastrointestinal cancer or who underwent elective diverticulitis surgery were excluded. Trends in HP were analyzed using multivariable linear regression, and factors associated with HP were assessed with multiple logistic regression. RESULTS: Of 499,433 patients who underwent colectomy in the emergency setting for acute diverticulitis, 271,288 (54.3%) had a HP and 228,145 (45.7%) had a PA. Median age was 61 years (IQR: 50-73), 53% were women, and 70.5% were white. The proportion of HP slightly increased over the study period-HP comprised 52.6% of included cases in 1993-98 and 55.2% of cases in 2014-2018 (p = 0.017). Advanced age (reference = 18-44 years; 45-54 years: OR 1.16, 95% CI 1.10-1.22; 55-64 years: OR 1.26, 95% CI 1.20-1.33; 65-74 years: OR 1.33, 95% CI 1.25-1.42; ≥ 75 years: OR 1.51, 95% CI 1.41-1.62), complicated diverticulitis (OR 1.41, 95% CI 1.36-1.46), and severity of illness (reference = minor; moderate: OR 1.46, 95% CI 1.38-1.54; major/extreme: OR 3.43, 95% CI 3.25-3.63) were associated with increased odds of HP. CONCLUSIONS: Over a 26-year period, HP has remained the most performed procedure in the emergency setting for diverticulitis. Future work should focus on knowledge translation with a possible change in practice as more randomized controlled trials provide support for PA.

Low Anterior Resection Syndrome in a Reference North American Sample: Prevalence and Associated Factors.

BACKGROUND: Low anterior resection syndrome (LARS) is a well-described consequence of rectal cancer treatment. Studying the degree to which bowel dysfunction exists in the general population may help to better interpret to what extent LARS is related to disease and/or cancer treatment. Currently, North American LARS normative data are lacking. The aim of this study was to describe the prevalence of bowel dysfunction, as measured by the LARS score, and quality of life (QoL) in a reference North American sample. Quality of life was measured and associations between participant characteristics and LARS were identified. STUDY DESIGN: This was a single-institution cross-sectional study of asymptomatic adults who underwent screening and surveillance colonoscopies from 2018 to 2021 with no/benign endoscopic findings. Survey was conducted on select comorbidities, sociodemographic factors, LARS, and QoL. Outcomes were LARS and QoL. Multivariable linear regression accounting for a priori clinical factors associated with bowel dysfunction was performed. RESULTS: Of 1,004 subjects approached, 502 (50.0%) participated, and 135 (26.9%) participants had major/minor LARS. On multiple linear regression, female sex (ß = 2.15, 95% CI 0.30 to 4.00), younger age (ß = -0.10, 95% CI -0.18 to -0.03), White ethnicity (ß = 2.45, 95% CI 0.15 to 4.74), and the presence of at least one of the following factors: diabetes, depression, neurologic disorder, or cholecystectomy (ß = 3.54, 95% CI 1.57 to 5.51) were independently associated with a higher LARS score. Individuals with LARS had lower global QoL, functional subscales, and various symptom subscale scores. CONCLUSIONS: Our study identified the baseline prevalence of LARS in asymptomatic adults who have not undergone a low anterior resection. These normative data will allow for more accurate interpretation of ongoing studies on LARS in North American rectal cancer patients.

Emergency colectomies in the NOAC era: a nationwide analysis demonstrating increased complications.

BACKGROUND: The use of Non-vitamin K antagonist oral anticoagulants (NOAC) has increased substantially since their introduction in 2010. The lack of readily available reversal agents poses a challenge in perioperative management. The aim of this study was to evaluate the impact of NOACs on the outcomes of emergency colectomies. METHODS: All adult patients on long-term anticoagulation who underwent emergency colectomies were identified from the Nationwide Inpatient Sample (NIS) database from 2002 to 2018. Long-term anticoagulation was defined using ICD-9/10 codes. Two cohorts were compared: anticoagulated patients in the pre-NOAC era (2002-2010) and anticoagulated patients in the NOAC era (2010-2018). Outcomes of interest were postoperative surgical complications, mortality and need for transfusion. RESULTS: Of 13,218 patients on long-term anticoagulation, 3,264 patients were treated in the pre-NOAC era and 9,954 in the NOAC era. Over the study period, there was a significant increase in the proportion of anticoagulated patients undergoing emergency colectomies (R2 = 0.91). On univariate analysis, anticoagulated patients in the NOAC era were medically more comorbid and had higher rates of postoperative surgical complications (73.3% vs 60.3%, p < 0.001) and mortality (8.2% vs. 6.7%, p = 0.006), but had lower rates of postoperative bleeding (3.5% vs. 4.4%, p = 0.002) and transfusions (38.1% vs. 45.4%, p < 0.001). On multivariable regression, after accounting for clinically significant covariates, anticoagulation in the NOAC era was associated with decreased rates of postoperative bleeding (OR 0.70, 95%CI 0.57-0.88) and transfusions (OR 0.71 95%CI 0.64-0.77) but remained an independent predictor of increased overall postoperative complications (OR 1.26, 95%CI 1.14-1.39). CONCLUSION: Prevalence of long-term anticoagulation in patients undergoing emergency colectomies is increasing. Although associated with lower rates of postoperative bleeding and transfusions, anticoagulation in the NOAC era is associated with higher rates of overall postoperative complications. Evidence-based guidelines for perioperative management of patients on NOACs in the emergency colorectal surgery setting are needed.

Oral Antibiotic Bowel Preparation Prior to Urgent Colectomy Reduces Odds of Organ Space Surgical Site Infections: a NSQIP Propensity-Score Matched Study.

BACKGROUND: Preoperative administration of oral antibiotic bowel preparation (OABP) alone has been shown to reduce infectious outcomes in patients undergoing elective colectomy. However, it remains unclear if these benefits extend to the emergency setting. This is a retrospective, propensity-score matched study comparing 30-day perioperative morbidity between those who received OABP alone versus no preparation prior to urgent colectomy. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, adults undergoing urgent colectomy from 2012 to 2019 were included. Those who were clinically obstructed or who received mechanical bowel preparation were excluded. Outcomes of interest included: surgical site infection (SSI), leak, ileus, and major morbidity. RESULTS: Of 24,559 patients meeting inclusion criteria, 878 (3.6%) received OABP prior to urgent colectomy. Prior to matching, those receiving no preparation were more likely to have higher ASA class, diabetes, hypertension, preoperative sepsis, open procedures, and a dirty wound classification. After matching, 1756 patients, remained with 878 in each arm. Preoperative characteristics were balanced on univariate analysis. Postoperatively, patients receiving OABP experienced decreased organ space SSI (11.2% vs. 15.5%, p = 0.009) and ileus (30.3% vs. 35.3%, p = 0.029), with no difference in leak rates (3.3% vs 3.3%, p = 1.000) or NSQIP major morbidity (47.4% vs. 49.9%, p = 0.316). On multivariate logistic regression, including propensity score, the reduction in organ space SSI associated with OABP persisted (OR 0.684, 95% CI 0.516-0.903). CONCLUSION: OABP prior to select urgent colectomies was associated with fewer organ space SSIs and may be considered when feasible.

The impact of delaying colonoscopies during the COVID-19 pandemic on colorectal cancer detection and prevention.

PURPOSE: The COVID-19 pandemic resulted in a partial to total shutdown of endoscopy in many healthcare centers. This study aims to quantify the impact of the reduction in colonoscopies on colorectal cancer (CRC) detection and screening. METHODS: After institutional ethics board approval, the endoscopy database at an academic tertiary-care center in Montreal, Canada, was searched for all colonoscopies performed from during the first wave locally (March-June 2020), and during the ramp up period where endoscopy service resumed (July to August 2020). We compared these periods to the same periods in 2019, the pre-pandemic periods. The indications, CRC and adenoma detection rates, as well as the prioritization of urgent procedures were compared. RESULTS: In the first wave, only 462 colonoscopies were performed, compared to 2515 in the same period in 2019, an 82% reduction. The ramp up period saw 843 colonoscopies performed compared to 1328 in 2019, a 35% reduction. Urgent and inpatient colonoscopies numbers increased (324 (24.8%) vs. 220 (5.7%)) while surveillance and high-risk screening colonoscopies fell (376 (28.8%) vs 1869 (48.6%)). Emergency access to colonoscopy was preserved with a median time to endoscopy of < 1 day (IQR 0,1) in both pandemic periods. During the pandemic periods, there was an absolute reduction in CRC diagnosis of 28, despite the CRC detection per colonoscopy rate increasing slightly in the first wave from 1.7% (44) to 3.9% (18), and in the ramp up period from 2.5% (33) to 3.6% (31). The rate of adenoma detection per colonoscopy did not increase significantly between the pre- and pandemic periods, resulting in reduction in adenoma removal in 723 patients. DISCUSSION: The restriction of access to colonoscopy resulted in a significant reduction in screening and surveillance of high-risk patients, adenomas removed, and CRCs diagnosed. Clinicians and patients will face the oncologic ramifications this the coming years.

Early discharge after colorectal cancer resection: trends and impact on patient outcomes.

BACKGROUND: Implementation of early discharge in colorectal surgery has been effective in improving patient satisfaction and reducing healthcare costs. Readmission rates following early discharge among colorectal cancer patients are believed to be low, however, remain understudied. The objectives of this study were: (i) to describe trends in early post-operative discharge and the associated hospitalization costs; (ii) to explore patient outcomes and resource utilization following early discharge; and (ii) to identify predictors of readmission following early discharge. METHODS: This was a retrospective cohort study using the Nationwide Readmissions Database. Adult patients admitted with a primary colorectal neoplasm who underwent colectomy or proctectomy between 2010 and 2017 were identified using ICD-9/10 codes. The exposure of interest was early post-operative discharge defined as ≤ 3 days from surgery. Main outcome measures were 30-day readmissions, post-operative complication rates, LOS and cost. RESULTS: In total, 342,242 patients were identified, and of those, 51,977 patients (15.2%) had early discharges. During the study period, the proportion of early discharges significantly increased (R2 = 0.94), from 9.9 to 23.4%, while readmission rates in this group remained unchanged (mean 7.3% ± 0.5). Complications that required bounceback readmission (within 7 days) after early discharge, rather than during index admission, were an independent predictor of longer overall LOS (ß = 0.044, p < 0.001) and higher hospitalization costs (ß = 0.031, p < 0.001). On multiple logistic regression, factors independently associated with bounceback readmission following early discharge were: male gender (OR = 1.47, 95%CI 1.33-1.63); open surgery (OR = 1.37, 95%CI 1.23-1.52); presence of stoma (OR = 1.51, 95%CI 1.22-1.87); transfer to facility or discharge with home health service (OR = 1.53, 95%CI 1.34-1.75); and Medicare/Medicaid insurance (OR = 1.34, 95%CI 1.14-1.57), among others. CONCLUSION: Early post-operative discharge of colorectal cancer patients is increasing despite a lack of improvement in readmission rates and an overall increase in hospitalization costs. Premature discharge of select patients may result in readmissions due to critical complications related to surgery resulting in increased resource utilization.

Segmental resection of splenic flexure colon cancers provides an adequate lymph node harvest and is a safe operative approach - an analysis of the ACS-NSQIP database.

INTRODUCTION: Fewer than 10% of colon cancers are found at the splenic flexure. A standard surgical approach to these cancers has not been defined. The goal of this study was to compare lymph node harvest and post-operative morbidity between segmental resection and formal left hemicolectomy for splenic flexure colon cancers. METHOD: Patients diagnosed with a splenic flexure cancer were identified from the 2012-2018 ACS-NSQIP colectomy-targeted database. Patients were categorized based on type of surgical resection - left hemicolectomy with colorectal anastomosis or segmental colectomy with colocolonic anastomosis. Demographic, clinicopathologic, and post-operative outcomes were compared between groups. Factors independently associated with lymph node harvest, operative time, and post-operative morbidity were investigated by linear and binomial logistic regression models. RESULTS: A total of 3,049 patients underwent colectomy for a splenic flexure cancer. Of these, 83.6% had a segmental colectomy and 73% were performed by a minimally invasive approach. T- and N-stage did not differ between segmental and left hemicolectomy groups (p = 0.703 and p = 0.429, respectively). Inadequate nodal harvest (< 12 nodes) was infrequent and similar between the two procedures (7.4% vs. 9.1%, p = 0.13). Operative time was significantly shorter for segmental colectomy (213 ± 83.5 min vs. 193 ± 84.1 min, p < 0.0001) and major morbidity was similar between the two surgical techniques (8.4% vs. 8.9%, p = 0.75). After accounting for demographic, clinicopathologic, and operative factors, binomial logistic regression showed that type of procedure was not significantly associated with LN harvest (OR 0.80, 95%CI 0.54-1.17) or major morbidity (OR 1.17, 95%CI 0.36-3.81). However, on linear regression, segmental splenic flexure resection was associated with shorter operative time (estimate 20.29, 95%CI 12.61-27.97, p < 0.0001). CONCLUSION: Splenic flexure resection for colon cancer is associated with an adequate lymph node harvest. Compared to a formal left hemicolectomy, a segmental resection also has a shorter operative time with equivalent post-operative morbidity.

Understanding the Burden of Colorectal Adenomas in Patients Younger Than 50 Years: A Large Single-Center Retrospective Cohort Study.

BACKGROUND: Colorectal cancer is increasing in young adults. Our understanding of the adenoma-carcinoma sequence in young patients aged <50 years is lacking. The yield obtained by lowering the age of screening colonoscopy remains unclear. OBJECTIVE: The goal of this study was to understand the burden and histology of colorectal polyps in young adults and to explore predictors of adenoma detection in this population. DESIGN: This is a retrospective cohort study. SETTING: Colonoscopies were performed at a single university-affiliated tertiary care center. PATIENTS: This study included adults aged <50 years who underwent a colonoscopy between 2014 and 2019. Patients with inflammatory bowel disease and genetic disorders were excluded. MAIN OUTCOME MEASURES: Adenoma detection rates were analyzed according to age. Predictors of adenoma detection were investigated by multiple logistic regression. RESULTS: A total of 4475 patients were analyzed. The mean age was 40.2 ± 8.0 years, 56.4% were female, and the mean BMI was 26.3 ± 5.5 kg/m2. A family history of colorectal cancer was reported in 23.8% of patients. The overall polyp and adenoma detection rates were 22% and 14%. The majority of polyps were adenomatous (58.9% of all polypectomies) and located in the left colon or rectum (61.4%). The detection rates of adenomas, advanced neoplasias, and adenocarcinomas were highest in patients aged 45 to 49 (19.3%, 4.8%, and 1.3%). On multivariate analysis, variables independently associated with adenoma detection included age (OR 1.08, 95% CI, 1.06-1.1), female sex (OR 1.80, 95% CI, 1.44-2.27), BMI (OR 1.01, 95% CI, 1.01-1.05), and having undergone a diagnostic colonoscopy (OR 1.81, 95% CI, 1.44-2.29). On subgroup analysis of patients aged 45 to 49, the same variables remained associated with adenoma detection except for age. LIMITATIONS: The study was limited due to the retrospective nature with heterogenous data. CONCLUSIONS: Adenoma detection in young adults aged 45 to 49 approaches the current adenoma detection of older adults. Predictors of adenoma detection in these young adults are female gender and BMI, which may help guide colorectal cancer screening guidelines in the future. See Video Abstract at http://links.lww.com/DCR/B843. COMPRENDER DE LA CARGA DE LOS ADENOMAS COLORRECTALES EN PACIENTES AOS UN ESTUDIO DE COHORTE RETROSPECTIVO DE UN SOLO CENTRO: ANTECEDENTES:El cáncer colorrectal está aumentando en adultos jóvenes. No se conoce la secuencia adenoma-carcinoma en pacientes jóvenes <50 años. El rendimiento obtenido al reducir la edad de la colonoscopia de detección sigue sin estar claro.OBJETIVO:Comprender la carga y la histología de los pólipos colorrectales en adultos jóvenes y explorar los predictores de detección de adenomas en esta población.DISEÑO:Estudio de cohorte retrospectivo.AJUSTE:Las colonoscopias se realizaron en un único centro de atención terciario afiliado a la universidad.PACIENTES:Adultos jóvenes <50 años que se sometieron a una colonoscopia entre 2014-2019. Se excluyeron los pacientes con enfermedad inflamatoria intestinal y trastornos genéticos.PRINCIPALES MEDIDAS DE RESULTADO:Se analizaron las tasas de detección de adenomas según la edad. Los predictores de la detección de adenomas se investigaron mediante regresión logística múltiple.RESULTADOS:Se analizaron 4475 pacientes. La edad media fue de 40,2 ± 8,0 años, el 56,4% eran mujeres y el IMC medio fue de 26,3 ± 5,5 kg / m2. Se informó de antecedentes familiares de cáncer colorrectal en el 23,8% de los pacientes. Las tasas generales de detección de pólipos y adenomas fueron del 22% y el 14%, respectivamente. La mayoría de los pólipos eran adenomatosos (58,9% de todas las polipectomías) y estaban localizados en colon izquierdo o recto (61,4%). Las tasas de detección de adenomas, neoplasias avanzadas y adenocarcinomas fueron más altas en pacientes de 45 a 49 años (19,3%, 4,8% y 1,3%, respectivamente). En el análisis multivariado, las variables asociadas de forma independiente con la detección de adenomas incluyeron: edad (OR 1.08; IC del 95%: 1,06-1,1), sexo femenino (OR 1,80; IC del 95%: 1,44-2,27), IMC (OR 1,01; IC del 95%: 1,01-1,05)) y haber sido sometido a una colonoscopia diagnóstica (OR 1,81; IC 95% 1,44-2,29). En el análisis de subgrupos de pacientes de 45 a 49 años, las mismas variables permanecieron asociadas con la detección de adenomas, excepto la edad.LIMITACIONES:Carácter retrospectivo con datos heterogéneos.CONCLUSIONES:La detección de adenomas en adultos jóvenes de 45 a 49 años se acerca a la detección actual de adenomas en adultos mayores. Los predictores de la detección de adenomas en estos adultos jóvenes son el sexo femenino y el IMC, que pueden ayudar a guiar las pautas de detección del cáncer colorrectal en el futuro. Consulte Video Resumen en http://links.lww.com/DCR/B843. (Traducción-Dr. Hagerman).

Development and Validation of a Clinical Risk Score for Intensive Care Resource Utilization After Colon Cancer Surgery: a Practical Guide to the Selection of Patients During COVID-19.

BACKGROUND: The purpose of this study was to develop and validate a prediction model and clinical risk score for Intensive Care Resource Utilization after colon cancer surgery. METHODS: Adult (≥ 18 years old) patients from the 2012 to 2018 ACS-NSQIP colectomy-targeted database who underwent elective colon cancer surgery were identified. A prediction model for 30-day postoperative Intensive Care Resource Utilization was developed and transformed into a clinical risk score based on the regression coefficients. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow goodness-of-fit test. The model was validated in a separate test set of similar patients. RESULTS: In total, 54,893 patients underwent an elective colon cancer resection, of which 1224 (2.2%) required postoperative Intensive Care Resource Utilization. The final prediction model retained six variables: age (≥ 70; OR 1.90, 95% CI 1.68-2.14), sex (male; OR 1.73, 95% CI 1.54-1.95), American Society of Anesthesiologists score (III/IV; OR 2.52, 95% CI 2.15-2.95), cardiorespiratory disease (yes; OR 2.22, 95% CI 1.94-2.53), functional status (dependent; OR 2.81, 95% CI 2.22-3.56), and operative approach (open surgery; OR 1.70, 95% CI 1.51-1.93). The model demonstrated good discrimination (AUC = 0.73). A clinical risk score was developed, and the risk of requiring postoperative Intensive Care Resource Utilization ranged from 0.03 (0 points) to 19.0% (8 points). The model performed well on test set validation (AUC = 0.73). CONCLUSION: A prediction model and clinical risk score for postoperative Intensive Care Resource Utilization after colon cancer surgery was developed and validated.

Euglycaemic ketoacidosis in a postoperative Whipple patient using canaglifozin.

SGLT2 inhibitors are a new class of oral antihyperglycaemic agents that have garnered much attention for their attractive efficacy profile in glycaemic control along with the added benefit of weight loss. There has been increasing concern for the risk of euglycaemic (serum glucose 4-8 mmol/L) ketoacidosis with these agents. In the setting of a postoperative patient, the use of these drugs may exacerbate the normal physiological stresses of the body and increase the risk of developing euglycaemic ketoacidosis (euKDA). This case highlights a postoperative patient who was using an SGLT2 inhibitor and developed severe euKDA after a pancreaticoduodenectomy. The goal of this case report was to bring awareness to the possibility of this rare adverse event. In doing so, it may aid in preoperative planning of the diabetic patient and trigger appropriate management for those who develop euKDA.

Interaction of anion exchanger 1 and glycophorin A in human erythroleukaemic K562 cells.

AE1 [anion exchanger 1, also known as SLC4A1 (solute carrier family 4, anion exchanger, member 1) and band 3 (erythrocyte membrane protein band 3)] is a major membrane glycoprotein expressed in human erythrocytes where it mediates the exchange of chloride and bicarbonate across the plasma membrane. Glycophorin A (GPA) is a sialoglycoprotein that associates with AE1 in erythrocytes forming the Wrb (Wright b) blood group antigen. These two integral proteins may also form a complex during biosynthesis, with GPA facilitating the cell surface expression of AE1. This study investigates the interaction of GPA with AE1 in K562 cells, a human erythroleukaemic cell line that expresses GPA, and the role of GPA in the cell surface expression of AE1. In K562 cells, GPA was dimeric and N- and O-glycosylated similar to erythroid GPA. GPA was localized at the cell surface, but also localized to the Golgi. AE1 expressed in K562 cells contained both complex and high-mannose oligosaccharides, and co-localized with GPA at the cell surface and in the endoplasmic reticulum (ER). The Wrb antigen was detected at the cell surface of AE1-transfected K562 cells, indicating the existence of an AE1-GPA complex. Immunofluorescence and co-immunoprecipitation studies using AE1 and an ER-localized hereditary spherocytosis mutant (R760Q AE1) showed that GPA and AE1 could interact in the ER. GPA knockdown by shRNAs (small-hairpin RNAs), however, had no effect on the level of cell surface expression of AE1. The results indicate that AE1 and GPA form a complex in the ER of human K562 cells, but that both proteins can also traffic to the cell surface independently of each other.

Structural characterization of the cytosolic domain of kidney chloride/bicarbonate anion exchanger 1 (kAE1).

Kidney anion exchanger 1 (kAE1) is a membrane glycoprotein expressed in alpha-intercalated cells in the collecting ducts of the kidney where it mediates electroneutral chloride/bicarbonate exchange. Human kAE1 is a truncated form of erythroid AE1 missing the first 65 residues of the N-terminal cytosolic domain, which includes a disordered acidic region (residues 1-54) and the first beta-strand (residues 55-65) of the folded region. Unlike erythroid AE1, kAE1 does not bind deoxyhemoglobin, glycolytic enzymes, or cytoskeletal components. To understand the effect of the N-terminal deletion on the structure of the cytosolic domain, we performed an extensive biophysical analysis on His 6 tagged cytosolic domains of erythroid AE1 (cdAE1), kidney AE1 (cdkAE1), and a novel truncation mutant (cdDelta54AE1) missing the first 54 residues, but retaining the beta-strand. Circular dichroism did not detect any major differences in secondary structure, and sedimentation analyses showed that all three proteins were dimeric. Differential scanning calorimetry revealed that cdAE1 and cdDelta54AE1 had similar thermal stabilities with midpoints of transition higher than cdkAE1. cdAE1 and cdDelta54AE1 underwent similar pH-dependent fluorescence changes, while cdkAE1 exhibited a higher intrinsic fluorescence at neutral and acidic pH. Urea denaturation resulted in dequenching of tryptophan fluorescence in cdAE1, while tryptophans in cdkAE1 were already dequenched in the native state. We conclude that the absence of the central beta-strand in cdkAE1 results in a less stable and more open structure than cdAE1. This structural change, in addition to the loss of the acidic amino-terminal region, may account for the altered protein binding properties of kAE1.