Postoperative Oral Rehydration and Regimented Follow-up Decrease Readmissions After Colorectal Surgery That Includes Ileostomies.

BACKGROUND: Ileostomies constitute 15% to 43% of readmissions after colorectal surgery, often due to dehydration and acute kidney injury. Prior institutional interventions decreased readmissions but not among patients who underwent new ileostomies. OBJECTIVE: To evaluate readmissions among patients who underwent new ileostomies after postoperative oral rehydration solution and standardized clinic visits. DESIGN: Retrospective analysis of prospective database. SETTINGS: Enhanced recovery colorectal surgery service. PATIENTS: Patients who underwent new ileostomy before and after intervention. INTERVENTIONS: Postoperative oral rehydration solution and postdischarge clinic visits with review of inputs/outputs, antimotility and appliance needs, and trained nurse reeducation 4 to 7 days after discharge, 30 days postoperatively, and every 1 to 2 weeks thereafter as needed. MAIN OUTCOME MEASURES: Readmission rate due to dehydration/acute kidney injury (primary), emergency department visits, and readmission rates overall and for specific diagnoses. Analysis used univariate and weighted techniques. RESULTS: A total of 312 patients (199 preintervention; 113 postintervention) were included, with a mean age of 59.0 years. Patients were predominantly White (94.9%) and evenly split between men and women. The most common diagnosis was diverticulitis (43.3%). The most common procedure was high anterior resection (38.8%), followed by low anterior resection (16.35%). Patient and procedure characteristics were well matched between groups. Multivariate analysis demonstrated that readmission rate due to dehydration/acute kidney injury significantly decreased between pre- and postintervention study groups (45.7% vs 16.5%, p = 0.039). Emergency department visits due to dehydration/acute kidney injury (12.0% vs 1.7%, p < 0.001) and readmissions from all causes (24.33% vs 10.6%, p = 0.005) also significantly decreased. Other complications were not significantly different between groups. Average stoma output 24 hours before (776 vs 625 mL, p = 0.005) and after (993 vs 890 mL, p = 0.025) discharge was significantly decreased in the postintervention group. LIMITATIONS: Retrospective single-center study. CONCLUSIONS: An oral rehydration solution and frequent standardized postdischarge visits led by trained nursing staff decreased readmissions and emergency department visits among patients who underwent new ileostomies after colorectal surgery. See Video Abstract . LA REHIDRATACIN ORAL POSOPERATORIA Y EL SEGUIMIENTO REGLAMENTADO REDUCEN LOS REINGRESOS EN PACIENTES DE CIRUGA COLORRECTAL CON ILEOSTOMAS: ANTECEDENTES:Las ileostomías constituyen del 15 al 43% de los reingresos después de la cirugía colorrectal, a menudo debido a la deshidratación y la lesión renal aguda. Las intervenciones institucionales previas redujeron los reingresos, pero no entre los pacientes con nuevas ileostomías.OBJETIVO:Evaluar los reingresos entre pacientes con nuevas ileostomías después del uso de solución de rehidratación oral postoperatoria y visitas clínicas estandarizadas.DISEÑO:Análisis retrospectivo de base de datos prospectiva.AJUSTES:Servicio de cirugía colorrectal de recuperación mejorada.PACIENTES:Pacientes con ileostomía nueva antes y después de la intervención.INTERVENCIÓN(ES):Solución de rehidratación oral posoperatoria y visitas clínicas posteriores al alta con revisión de entradas/salidas, antimotilidad y necesidades de aparatos, y reeducación de enfermeras capacitadas 4-7 días después del alta, 30 días después de la operación y cada 1-2 semanas después, según sea necesario.PRINCIPALES MEDIDAS DE RESULTADO:Tasa de readmisión debido a deshidratación/lesión renal aguda (primaria), tasa de urgencias y de readmisión en general y para diagnósticos específicos. El análisis utilizó técnicas univariadas y ponderadas.RESULTADOS:Se incluyeron un total de 312 pacientes (199 preintervención; 113 postintervención), con una edad media de 59,0 años. Los pacientes eran predominantemente blancos (94,9%) y se dividieron equitativamente entre hombres y mujeres. El diagnóstico más frecuente fue diverticulitis (43,3%). El procedimiento más común fue la resección anterior alta (38,8 %) seguida de la resección anterior baja (16,35 %). Las características del paciente y del procedimiento coincidieron bien entre los grupos. El análisis multivariante demostró que la tasa de reingreso debido a deshidratación/lesión renal aguda disminuyó significativamente entre los grupos de estudio antes y después de la intervención (45,7 % frente a 16,5 %, p = 0,039). Las visitas a urgencias por deshidratación/insuficiencia renal aguda (12,0 % frente a 1,7 %, p < 0,001) y los reingresos por todas las causas (24,33 % frente a 10,6 %, p = 0,005) también disminuyeron significativamente. Otras complicaciones no fueron significativamente diferentes entre los grupos. El gasto medio del estoma 24 horas antes (776 ml frente a 625 ml, p = 0,005) y después (993 ml frente a 890 ml, p = 0,025) del alta disminuyó significativamente en el grupo posterior a la intervención.LIMITACIONES:Estudio retrospectivo de centro único.CONCLUSIONES:Una solución de rehidratación oral y frecuentes visitas estandarizadas posteriores al alta dirigidas por personal de enfermería capacitado redujeron los reingresos y las visitas al servicio de urgencias entre los pacientes con nuevas ileostomías después de la cirugía colorrectal. ( Traducción-Dr. Yolanda Colorado ).

Alvimopan is associated with favorable outcomes in open and minimally invasive colorectal surgery: a regional database analysis.

BACKGROUND: Alvimopan is a µ-opioid receptor antagonist associated with shorter time to gastrointestinal recovery in patients having open colorectal surgery. Data demonstrating the benefit of perioperative alvimopan for the minimally invasive surgical approach are inconsistent. The aim of this study is to determine colorectal surgery groups that benefit from perioperative alvimopan. METHODS: This is a retrospective cohort analysis of colorectal surgery patients who had, and patients who did not have, perioperative alvimopan in the Michigan Surgical Quality Collaborative regional risk-adjusted database from 2018 through 2021. Main outcome measures were postoperative length of hospital stay, time to return of bowel function, and postoperative ileus. RESULTS: There were 10,010 patients (30.3% open, 40.5% laparoscopic, 12.7% hand-assist laparoscopic, 43.5% robotic) who met inclusion criteria-4919 received alvimopan in the perioperative period and 5091 did not. When compared to those not receiving alvimopan, unadjusted outcomes showed that the alvimopan group had significantly shorter postoperative length of stay (4.75 days vs 5.5 days, p < 0.001), shorter time to return of bowel function (1.61 days vs 2.01 days, p < 0.001) and less postoperative ileus (5.45% vs 7.94%, p < 0.001). After adjustment, regression models confirmed that alvimopan was associated with an 9.6% reduction in hospital length of stay (p < 0.001), a 14.9% shorter time to return of bowel function (p < 0.001), and a 42.1% reduction in postoperative ileus (p < 0.001). Subgroup analysis showed significant benefit of alvimopan for all three outcomes in patients having the minimally invasive approach. CONCLUSIONS: Alvimopan is associated with shorter hospital length of stay, shorter time to return of bowel function, and decreased postoperative ileus when administered to patients undergoing colorectal surgery. Benefit is not limited to the open approach and includes minimally invasive laparoscopic and robotic colorectal procedures.

Myocardial infarction after craniotomy for asymptomatic meningioma.

A man in his 40s with a history of coronary artery disease previously treated with a drug-eluting stent presented for elective craniotomy and resection of an asymptomatic but enlarging meningioma. During his craniotomy, he received desmopressin and tranexamic acid for surgical bleeding. Postoperatively, the patient developed chest pain and was found to have an ST-elevation myocardial infarction (MI). Because of the patient's recent neurosurgery, standard post-MI care was contraindicated and he was instead managed symptomatically in the intensive care unit. Echocardiogram on postoperative day 1 demonstrated no regional wall motion abnormalities and an ejection fraction of 60%. His presentation was consistent with thrombosis of his diagonal stent. He was transferred out of the intensive care unit on postoperative day 1 and discharged home on postoperative day 3.

Acute Colonic Pseudo-Obstruction.

CASE SUMMARY: A 33-year-old man with a history of chronic alcohol use, generalized anxiety disorder, and hypertension presented to the emergency department after a syncopal event. He was admitted to the medical intensive care unit for alcohol withdrawal, requiring intubation and sedation. On hospital day 7, abdominal x-ray image demonstrated a dilated cecum to 12 cm, transverse colon dilation to 7 cm, and decompressed distal colon ( Fig. 1 ). CT scan of the abdomen and pelvis confirmed dilation of the cecum and ascending and transverse colons ( Fig. 2 ). Colonoscopy showed no evidence of distal obstruction, but colonic distension persisted, and he subsequently underwent cecal decompression with an open "blow-hole" cecostomy fully matured at skin level via a small right lower quadrant incision. The nasogastric tube was removed on postoperative day 2, and his diet was slowly advanced. Abdominal x-ray image on postoperative day 5 demonstrated no colonic dilation. He was discharged home on postoperative day 7. The patient re-presented to the hospital 3 months later with cecostomy prolapse. He underwent cecostomy takedown with ileocecectomy via circumstomal incision. He was discharged home on postoperative day 2.

Rare case of rectosigmoid stricture causing transverse colon volvulus.

A 60-year-old woman with remote history of sleeve gastrectomy presented with altered mental status after an unwitnessed fall. She was found to be hypothermic with lactic acidaemia, leucocytosis, positive urinalysis, and dilated ascending and transverse colon on cross-sectional imaging, initially thought to be secondary to faecal loading. She was admitted to the medical intensive care unit for resuscitation and broad-spectrum antibiotics for presumed urinary sepsis. She became acutely altered and underwent urgent flexible sigmoidoscopy by gastroenterology to evaluate for ischaemic colitis. During the procedure, there was concern for iatrogenic colon injury given the friability of the colonic mucosa, so the patient was taken urgently for exploratory laparotomy. Intraoperatively, she was found to have a transverse colon volvulus with large areas of patchy, gangrenous bowel without evidence of gross perforation. A rectosigmoid stricture with associated serosal tear, but no full-thickness injury was identified. An extended left hemicolectomy and end transverse colostomy was performed resulting in improvement in the patient's clinical status and eventual discharge to subacute rehab.

Computed Tomography for Acute Appendicitis Diagnosis and Confirmation in Men : Trends and Cost Implications.

INTRODUCTION: The classic findings of acute appendicitis-right lower quadrant pain, anorexia, and leukocytosis-have been well known. However, emergency medicine and surgical providers continue to rely on imaging to confirm the diagnosis. We aimed to evaluate the increase in reliance on computed tomography (CT) scans for acute appendicitis diagnosis over time. METHODS: We conducted a retrospective study of patients ≥18 years presenting to UNC Hospitals with signs and symptoms of acute appendicitis who subsequently underwent appendectomy from 2011 to 2015. Demographic, clinical, laboratory, and pathologic data were reviewed. We evaluated the incidence of CT scans stratified by year, age, and sex. RESULTS: Within our male population, 55.2% (278/504) had classic appendicitis symptoms. Of the 278 male patients with classic appendicitis symptoms, 248 underwent CT imaging. Male patients <45 years of age were more likely to present with classic appendicitis symptoms (216/357, 60.5%) compared with patients aged 46-65 (52/108, 48.1%) or >65 (10/39, 25.6%). Of the male patients <45 years with classic appendicitis symptoms, the incidence of CT scans increased over time (68.3% in 2011, 84.2% in 2012, 92.3% in 2013, 93.9% in 2014, 92.3% in 2015). When considering the 216 CT scans that could have been avoided in our population, we calculate an approximate savings of $173 998.80 over 5 years. CONCLUSION: The incidence of CT scans for acute appendicitis confirmation has increased over time even in men. CT scans for the diagnosis or confirmation of acute appendicitis should rarely be indicated in men aged <45 years with classic appendicitis symptoms.

Regulation of Na/K-ATPase expression by cholesterol: isoform specificity and the molecular mechanism.

We have reported that the reduction in plasma membrane cholesterol could decrease cellular Na/K-ATPase α1-expression through a Src-dependent pathway. However, it is unclear whether cholesterol could regulate other Na/K-ATPase α-isoforms and the molecular mechanisms of this regulation are not fully understood. Here we used cells expressing different Na/K-ATPase α isoforms and found that membrane cholesterol reduction by U18666A decreased expression of the α1-isoform but not the α2- or α3-isoform. Imaging analyses showed the cellular redistribution of α1 and α3 but not α2. Moreover, U18666A led to redistribution of α1 to late endosomes/lysosomes, while the proteasome inhibitor blocked α1-reduction by U18666A. These results suggest that the regulation of the Na/K-ATPase α-subunit by cholesterol is isoform specific and α1 is unique in this regulation through the endocytosis-proteasome pathway. Mechanistically, loss-of-Src binding mutation of A425P in α1 lost its capacity for regulation by cholesterol. Meanwhile, gain-of-Src binding mutations in α2 partially restored the regulation. Furthermore, through studies in caveolin-1 knockdown cells, as well as subcellular distribution studies in cell lines with different α-isoforms, we found that Na/K-ATPase, Src, and caveolin-1 worked together for the cholesterol regulation. Taken together, these new findings reveal that the putative Src-binding domain and the intact Na/K-ATPase/Src/caveolin-1 complex are indispensable for the isoform-specific regulation of Na/K-ATPase by cholesterol.

Epithelial and Endothelial Adhesion of Immune Cells Is Enhanced by Cardiotonic Steroid Signaling Through Na+/K+-ATPase-α-1.

Background Recent studies have highlighted a critical role for a group of natriuretic hormones, cardiotonic steroid (CTS), in mediating renal inflammation and fibrosis associated with volume expanded settings, such as chronic kidney disease. Immune cell adhesion is a critical step in the inflammatory response; however, little is currently understood about the potential regulatory role of CTS signaling in this setting. Herein, we tested the hypothesis that CTS signaling through Na+/K+-ATPase α-1 (NKA α-1) enhances immune cell recruitment and adhesion to renal epithelium that ultimately advance renal inflammation. Methods and Results We demonstrate that knockdown of the α-1 isoform of Na/K-ATPase causes a reduction in CTS-induced macrophage infiltration in renal tissue as well reduces the accumulation of immune cells in the peritoneal cavity in vivo. Next, using functional adhesion assay, we demonstrate that CTS-induced increases in the adhesion of macrophages to renal epithelial cells were significantly diminished after reduction of NKA α-1 in either macrophages or renal epithelial cells as well after inhibition of NKA α-1-Src signaling cascade with a specific peptide inhibitor, pNaKtide in vitro. Finally, CTS-induced expression of adhesion markers in both endothelial and immune cells was significantly inhibited in an NKA α-1-Src signaling dependent manner in vitro. Conclusions These findings suggest that CTS potentiates immune cell migration and adhesion to renal epithelium through an NKA α-1-dependent mechanism; our new findings suggest that pharmacological inhibition of this feed-forward loop may be useful in the treatment of renal inflammation associated with renal disease.

Appendiceal Malignancy: The Hidden Risks of Nonoperative Management for Acute Appendicitis.

One potential harm of nonoperative management for acute appendicitis is missed appendiceal cancer, a rare and often aggressive malignancy due to the frequency of late stage of diagnosis. Previous studies have reported an increasing incidence of appendiceal neoplasms in the population. This is a retrospective case-control study of 1007 adult patients, who presented to the University of North Carolina-Memorial Hospital (UNC-MH) between 2011 and 2015 with clinical signs and symptoms of appendicitis. We evaluated the incidence of primary appendiceal cancer in this population and determined factors that predict appendiceal cancer diagnosis using multivariate logistic regression analysis. The overall incidence of appendiceal neoplasm for adult patients presenting to UNC-MH with appendicitis from 2011 to 2015 was 2.3 per cent (23/1007). The incidence in patients without appendiceal perforation on pathology was 1.9 per cent (16/832). Age (odds ratio (OR) 1.03), number of days of abdominal pain (OR 1.16), self-reported fever (OR 2.08), appendiceal width (OR 1.95), and appendiceal wall thickness (OR 1.30) were predictors of appendiceal neoplasm diagnosis in patients that present with acute appendicitis. We recommend that an operative approach to acute appendicitis should remain the standard of care because operative management may not only be diagnostic but potentially therapeutic.

Telocinobufagin, a Novel Cardiotonic Steroid, Promotes Renal Fibrosis via Na⁺/K⁺-ATPase Profibrotic Signaling Pathways.

Cardiotonic steroids (CTS) are Na⁺/K⁺-ATPase (NKA) ligands that are elevated in volume-expanded states and associated with cardiac and renal dysfunction in both clinical and experimental settings. We test the hypothesis that the CTS telocinobufagin (TCB) promotes renal dysfunction in a process involving signaling through the NKA α-1 in the following studies. First, we infuse TCB (4 weeks at 0.1 µg/g/day) or a vehicle into mice expressing wild-type (WT) NKA α-1, as well as mice with a genetic reduction (~40%) of NKA α-1 (NKA α-1+/-). Continuous TCB infusion results in increased proteinuria and cystatin C in WT mice which are significantly attenuated in NKA α-1+/- mice (all p < 0.05), despite similar increases in blood pressure. In a series of in vitro experiments, 24-h treatment of HK2 renal proximal tubular cells with TCB results in significant dose-dependent increases in both Collagens 1 and 3 mRNA (2-fold increases at 10 nM, 5-fold increases at 100 nM, p < 0.05). Similar effects are seen in primary human renal mesangial cells. TCB treatment (100 nM) of SYF fibroblasts reconstituted with cSrc results in a 1.5-fold increase in Collagens 1 and 3 mRNA (p < 0.05), as well as increases in both Transforming Growth factor beta (TGFb, 1.5 fold, p < 0.05) and Connective Tissue Growth Factor (CTGF, 2 fold, p < 0.05), while these effects are absent in SYF cells without Src kinase. In a patient study of subjects with chronic kidney disease, TCB is elevated compared to healthy volunteers. These studies suggest that the pro-fibrotic effects of TCB in the kidney are mediated though the NKA-Src kinase signaling pathway and may have relevance to volume-overloaded conditions, such as chronic kidney disease where TCB is elevated.

The Impact on Resource Utilization of Supportive Care Consults on Patients at the University of North Carolina Hospital, 2010-2012.

BACKGROUND: Cancer patients have a high rate of emergency department (ED) visits and inpatient hospitalizations (IHs) that may be reduced by use of outpatient palliative care services. OBJECTIVE: To determine whether the outpatient adult palliative care service at the University of North Carolina (UNC) Hospital, begun in 2008, reduced the frequency of ED visits and IH during a two-year period. DESIGN: The charts of patients with lung cancer or head and neck cancer seen by the supportive care service from 2010 to 2011, and of a contemporaneous set of potential consults that were not seen, were retrospectively reviewed to determine the impact of this care delivery model. SETTING/SUBJECTS: The number of individuals with lung cancer and head cancer seen during this two-year period was 24 and 23, respectively, permitting a statistical analysis from which meaningful conclusions could be drawn. MEASUREMENTS: The frequency of ED visits and IHs for each patient was reviewed. Descriptive statistics were used. Fisher's exact test was used for data categorized into two by two contingency tables. The nonparametric Jonckheere-Terpstra method was used to test for ordered differences across categories. RESULTS: Consultation with supportive care did not decrease overall use of ED visits. Patients with head and neck cancer showed an increase in ED visits (p = 0.08) but a reduction in inpatient admissions (p = 0.0004). In patients with lung cancer, the opposite effect was seen-an increase in inpatient visits (p = 0.02) but a decrease in ED visits. The frequency of ED visits was correlated with distance to the ED (p = 0.02), a finding that has not been noted before. CONCLUSIONS: Further work is needed to define the best model for outpatient palliative care.

MicroRNA expression differentiates squamous epithelium from Barrett's esophagus and esophageal cancer.

BACKGROUND: Current strategies fail to identify most patients with esophageal adenocarcinoma (EAC) before the disease becomes advanced and incurable. Given the dismal prognosis associated with EAC, improvements in detection of early-stage esophageal neoplasia are needed. AIM: We sought to assess whether differential expression of microRNAs could discriminate between squamous epithelium, Barrett's esophagus (BE), and EAC. METHODS: We analyzed microRNA expression in a discovery cohort of human endoscopic biopsy samples from 36 patients representing normal squamous esophagus (n = 11), BE (n = 14), and high-grade dysplasia/EAC (n = 11). RNA was assessed using microarrays representing 847 human microRNAs followed by quantitative real-time polymerase chain reaction (qRT-PCR) verification of nine microRNAs. In a second cohort (n = 18), qRT-PCR validation of five miRNAs was performed. Expression of 59 microRNAs associated with BE/EAC in the literature was assessed in our training cohort. Known esophageal cell lines were used to compare miRNA expression to tissue miRNAs. RESULTS: After controlling for multiple comparisons, we found 34 miRNAs differentially expressed between squamous esophagus and BE/EAC by microarray analysis. However, miRNA expression did not reliably differentiate non-dysplastic BE from EAC. In the validation cohort, all five microRNAs selected for qRT-PCR validation differentiated between squamous samples and BE/EAC. Microarray results supported 14 of the previously reported microRNAs associated with BE/EAC in the literature. Cell lines did not generally reflect miRNA expression found in vivo. CONCLUSIONS: These data indicate that miRNAs differ between squamous esophageal epithelium and BE/EAC, but do not distinguish between BE and EAC. We suggest prospective evaluation of miRNAs in patients at high risk for EAC.

CD36 and Na/K-ATPase-α1 form a proinflammatory signaling loop in kidney.

Proatherogenic, hyperlipidemic states demonstrate increases in circulating ligands for scavenger receptor CD36 (eg, oxidized low-density lipoprotein [oxLDL]) and the Na/K-ATPase (eg, cardiotonic steroids). These factors increase inflammation, oxidative stress, and progression of chronic kidney disease. We hypothesized that diet-induced obesity and hyperlipidemia potentiate a CD36/Na/K-ATPase-dependent inflammatory paracrine loop between proximal tubule cells (PTCs) and their associated macrophages and thereby facilitate development of chronic inflammation and tubulointerstitial fibrosis. ApoE(-/-) and apoE(-/-)/cd36(-/-) mice were fed a high-fat diet for ≤32 weeks and examined for physiologic and histologic changes in renal function. Compared with apoE(-/-), apoE(-/-)/cd36(-/-) mice had improved creatinine clearance and blood pressure which corresponded histologically with less glomerular and tubulointerstitial macrophage accumulation, foam cell formation, oxidant stress, and interstitial fibrosis. Coimmunopreciptation and a cell surface fluorescence-based crosslinking assay showed that CD36 and Na/K-ATPase α-1 colocalized in PTCs and macrophages, and this association was increased by oxLDL or the cardiotonic steroid ouabain. OxLDL and ouabain also increased activation of Src and Lyn in PTCs. Cell-free conditioned medium from PTCs treated with oxLDL or ouabain increased macrophage migration. OxLDL, ouabain, or plasma isolated from high-fat diet-fed mice stimulated reactive oxygen species production in PTCs, which was inhibited by N-acetyl-cysteine, apocynin, or Na/K-ATPase α-1 knockdown. These data suggest that ligands generated in hyperlipidemic states activate CD36 and the Na/K-ATPase and potentiate an inflammatory signaling loop involving PTCs and their associated macrophages, which facilitates the development of chronic inflammation, oxidant stress, and fibrosis underlying the renal dysfunction common to proatherogenic, hyperlipidemic states.

A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling.

AIMS: Obesity and hyperlipidaemia are associated with insulin resistance (IR); however, the mechanisms responsible remain incompletely understood. Pro-atherogenic hyperlipidaemic states are characterized by inflammation, oxidant stress, and pathophysiologic oxidized lipids, including ligands for the scavenger receptor CD36. Here we tested the hypothesis that the absence of CD36 protects mice from IR associated with diet-induced obesity and hyperlipidaemia. METHODS AND RESULTS: Adipose tissue from CD36(-/-) mice demonstrated a less inflammatory phenotype and improved insulin signalling in vivo and at the level of the adipocyte and macrophage. The pathophysiologic ligand oxidized low-density lipoprotein (oxLDL) activated c-Jun N-terminal kinase (JNK) and disrupted insulin signalling in both adipocytes and macrophages in a CD36-dependent manner. Macrophages isolated from CD36(-/-) mice after high-fat diet feeding elicited less JNK activation and inhibition of insulin signalling in adipocytes after co-culture compared with wild-type macrophages. CONCLUSION: These data suggest that a CD36-dependent inflammatory paracrine loop between adipocytes and macrophages facilitates chronic inflammation and contributes to IR common in obesity and dyslipidaemia.