A Retrospective Cohort Analysis of Two Computerized Insulin Infusion Protocols.

OBJECTIVE: The primary objective of this analysis was to compare the safety and efficacy of a novel computerized insulin infusion protocol (CIIP), the Lalani Insulin Infusion Protocol (LIIP), with an established CIIP, Glucommander. METHODS: We conducted a 10-month retrospective analysis of 778 patients in whom LIIP was used (August 18, 2020 to June 25, 2021) at six HonorHealth Hospitals in the Phoenix metropolitan area. These data were compared with Glucommander that was used at those same hospitals from January 1, 2018 to August 17, 2020, n = 4700. Primary end points of the project included average time to euglycemia and average time in hyperglycemia (>180 mg/dL) and hypoglycemia (<70 mg/dL). Additional subgroup analysis was done to evaluate CIIP performance in patients in whom maintenance of euglycemia was more challenging. RESULTS: The LIIP had a faster time to euglycemia (191 vs 222 minutes, P < .001) and similar time in hypoglycemia (2.79 vs 2.76 minutes, P = .50) for all patients, when compared with Glucommander. Similar observations were made for the following subgroups: diabetic ketoacidosis/hyperosmolar hyperglycemic state (DKA/HHS) patients, COVID-19 patients, patients on steroids, patients with ≥60 glomerular filtration rate (GFR), patients with renal insufficiency, and patients with sepsis. CONCLUSIONS: The LIIP is a safe and effective CIIP in managing intravenous insulin infusion rates. Utilization of LIIP resulted in reduced time to euglycemia, P < .001, when compared with Glucommander and did not cause increased hypoglycemia during the project period. Contributing factors to the success of LIIP may include improved clinical workflow, learnability and ease of use, compatibility with the Epic electronic health record (EHR), and its unique, dynamic and adaptive algorithm.

Immune cell profiles of patients with interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disorder characterized by bladder pain upon filling which severely affects quality of life. Clinical presentation can vary. Local inflammatory events typify the clinical presentation of IC/BPS patients with Hunner lesions (IC/BPS-HL). It has previously been proposed that B cells are more prevalent in HL, but understanding their exact role in this environment requires a more complete immunological profile of HL. We characterized immunological dysfunction specifically in HL using immunohistochemistry. We detected significantly more plasma cells (50× increase, p < 0.0001), B cells (28× increase, p < 0.0001), T cells (3× increase, p < 0.0001), monocytes/macrophages (6× increase, p < 0.0001), granulocytes (4× increase, p < 0.0001), and natural killer cells (2× increase, p = 0.0249) in IC/BPS patients with HL than in unaffected controls (UC). Patients with IC/BPS-HL also had significantly elevated urinary levels of IL-6 (p = 0.0054), TNF-α (p = 0.0064) and IL-13 (p = 0.0304) compared to patients with IC/BPS without HL (IC/BPS-NHL). In contrast, IL-12p70 levels were significantly lower in the patients with HL than in those without these lesions (p = 0.0422). Different cytokines were elevated in the urine of IC/BPS patients with and without HL, indicating that different disease processes are active in IC/BPS patients with and without HL. Elevated levels of CD138+, CD20+, and CD3+ cells in HL are consistent B and T-cell involvement in disease processes within HL.

Considerations for an Alternative Site of Islet Cell Transplantation.

Islet cell transplantation has been limited most by poor graft survival. Optimizing the site of transplantation could improve clinical outcomes by minimizing required donor cells, increasing graft integration, and simplifying the transplantation and monitoring process. In this article, we review the history and significant human and animal data for clinically relevant sites, including the liver, spleen, and kidney subcapsule, and identify promising new sites for further research. While the liver was the first studied site and has been used the most in clinical practice, the majority of transplanted islets become necrotic. We review the potential causes for graft death, including the instant blood-mediated inflammatory reaction, exposure to immunosuppressive agents, and low oxygen tension. Significant research exists on alternative sites for islet cell transplantation, suggesting a promising future for patients undergoing pancreatectomy.

Time-Effect of Donor and Recipient Characteristics on Graft Survival after Kidney Transplantation.

The kidney allocation system (KAS) is based on quality-based "longevity matching" strategies that provide only a momentary snapshot of expected outcomes at the time of transplantation. The purpose of our study was to define on a continuous timeline the relative and mutual interactions of donor and recipient characteristics on graft survival. Total 39,108 subjects who underwent kidney transplant between October 25, 1999 and January 1, 2007 were identified in the United Network for Organ Sharing dataset. Our primary outcome was graft survival. Time-dependent receiver operating characteristic (ROC) curves and area under time-dependent ROC curve (AUC) were used to compare the predictive ability of the two allocation systems. During the first year after transplantation, both donor and recipient models showed identical relevance. From the first to the sixth years, although the two ROC curves were nearly identical, the donor model outweighed the recipient model. Both models intersected again at the sixth year. From that time onward, the ROC curve for recipient characteristics model predominated over the ROC curve for donor characteristics model. The predictive value of the recipient model (AUC = 0.752) was greater than that of the donor model (AUC = 0.673) We hope that this model will provide additional guidance and risk stratification to further optimize organ allocation based on the dynamic interaction of both donor and recipient characteristics over time.

Impact of Drain Placement and Duration on Outcomes After Pancreaticoduodenectomy: A National Surgical Quality Improvement Program Analysis.

BACKGROUND: The decisions to routinely place a drain after pancreaticoduodenectomy and how long to leave the drain remain controversial due to conflicting evidence and significant variations in clinical practice. This study aims to address those questions by using a large national database and a rigorous analytical model. METHODS: The American College of Surgeons National Surgical Quality Improvement Program 2015-2016 Pancreatectomy Participant Use Data Files were used to identify patients who had undergone pancreaticoduodenectomy (n = 7583). Univariable and multivariable binomial regression analyses were performed to control for potential confounders and various preoperative risk factors. Cox regression with drain as a time-dependent covariate, conditional on having a drain placed, was used to examine the association between the drain remaining in place and morbidities. RESULTS: Of 7583 patients, drains were placed in 6666 (87.9%). Drain placement decreased the risk of developing serious morbidity (relative risk [RR] 0.73, 95% confidence interval [CI] 0.65-0.82), overall morbidity (RR 0.79, 95% CI 0.72-0.87), and organ space surgical site infection (RR 0.72, 95% CI 0.61-0.85). Drain placement did not change the risk of developing a clinically relevant postoperative pancreatic fistula (RR 0.96, 95% CI 0.78-1.19). However, for those with drains placed, length of drainage was independently associated with serious morbidity (hazard ratio [HR] 3.06, 95% CI 2.65-3.53), overall morbidity (HR 2.48, 95% CI 2.20-2.80), and organ space surgical site infection (HR 1.47, 95% CI 1.23-1.74). CONCLUSIONS: Routine drain placement following pancreaticoduodenectomy may decrease postoperative complications, including serious morbidity, overall morbidity, and organ space surgical site infections; however, length of drainage was associated with increased risk of the previously-named complications. These results support the routine placement and early removal of intraoperative surgical drains in pancreaticoduodenectomy.

Maximizing the Use of Scoring Systems in the Prediction of Outcomes in Acute Pancreatitis.

BACKGROUND/AIMS: No single classification system has so far effectively predicted the severity for Acute Pancreatitis (AP). This study compares the effectiveness of classification systems: Original Atlanta (OAC), Revised Atlanta (RAC), Determinant based classification (DBC), PANC 3, Harmless AP Score (HAPS), Japanese Severity Score (JSS), Symptoms Nutrition Necrosis Antibiotics and Pain (SNNAP), and Beside Index of Severity for AP (BISAP) in predicting outcomes in AP. METHODS: Scores for BISAP, Panc 3, HAPS, SNNAP, OAC, RAC, and DBC were calculated for 221 adult patients hospitalized for AP. Receiver Operating Characteristic curve analysis and Akaike Information Criteria were used to compare the effectiveness of predicting need for surgery, intensive care unit (ICU) admission, readmission within 30 days, and length of hospital stay. RESULTS: Both the RAC and the DBC strongly predict the length of hospital stay (p < 0.0001 for both) and ICU admission (p < 0.0001 for both). Additionally, both BISAP and PANC 3 showed weak predictive capacity at identifying length of stay and ICU admission. CONCLUSIONS: We suggest that BISAP and PANC3 be obtained within the initial 24 h of hospitalization to offer an early prediction of length of stay and ICU admission. Subsequently, RAC and DBC can offer further information later in the course of the disease.

Validation of Lipase and Systemic Inflammatory Response Syndrome as Prognostic Indicators in Pediatric Acute Pancreatitis: A Retrospective Analysis.

INTRODUCTION: Acute pancreatitis (AP) is understudied in the pediatric population despite increasing incidence. Although many cases are mild and resolve with supportive care, severe acute pancreatitis (SAP) can be associated with significant morbidity and mortality. There is a lack of pediatric-specific predictive tools to help stratify risk of SAP in children. METHODS: A retrospective cohort study of patients with AP or recurrent AP at Cohen Children's Medical Center between 2011 and 2016 was performed. Lipase level and the presence of pediatric systemic inflammatory response syndrome (SIRS) on admission were examined as potential predictors of SAP and length of stay (LOS). A multivariate logistic regression or analysis of covariance was used to conduct the multivariate analysis. RESULTS: Seventy-nine pediatric patients met inclusion criteria. Approximately 37% (29/79) had SIRS on admission, 22% (17/79) developed SAP, and there were no mortalities. In both the univariate and multivariate models, SIRS was a predictor of SAP. Mean (SD) LOS for patients with SIRS compared with without SIRS was 9.6 ±â€Š8.3 compared with 6.3 ±â€Š6.9 days (P < 0.05). The mean LOS of patients with one or more comorbidity (48%, 38/79) was 10.0 ±â€Š9.5 compared with 5.2 ±â€Š4.0 days (P < 0.01) for those patients without any comorbidities. Only the presence of comorbidities predicted length of time spent nil per os (NPO; P = 0.0022). Patients with comorbidities stayed an average of 5.6 ±â€Š7.6 days NPO, whereas those without comorbidities spent 2.8 ±â€Š2.4 days NPO. Lipase was not predictive of SAP, LOS, or length of time spent NPO. CONCLUSIONS: These results support the use of SIRS as a simple screening tool on admission to identify children at risk for the development of SAP. The presence of any comorbidity was predictive of LOS and length of NPO in the multivariate model. This may reflect that comorbidities prolong pancreatitis or influence disposition planning.

Predictors of 30-day readmission following pancreatic surgery: A retrospective review.

BACKGROUND: Pancreatectomies have been identified as procedures with an increased risk of readmission. In surgical patients, readmissions within 30 days of discharge are usually procedure-related. We sought to determine predictors of 30-day readmission following pancreatic resections in a large healthcare system. METHODS: We retrospectively collected information from the records of 383 patients who underwent pancreatic resections from 2004-2013. To find the predictors of readmission in the 30 days after discharge, we performed a univariate screen of possible variables using the Fisher's exact test for categorical variables and the Mann-Whitney U test for continuous variables. Multivariate analysis was used to determine the independent factors. RESULTS: Fifty-eight (15.1%) patients were readmitted within 30 days of discharge. Of the patients readmitted, the most common diagnoses at readmission were sepsis (17.2%), and dehydration (8.6%). Multivariate logistic regression found that the development of intra-abdominal fluid collections (OR = 5.32, P < 0.0001), new thromboembolic events (OR = 4.08, P = 0.016), and pre-operative BMI (OR = 1.06, P = 0.040) were independent risk factors of readmission within 30 days of discharge. CONCLUSION: Our data demonstrate that factors predictive of 30-day readmission are a combination of patient characteristics and the development of post-operative complications. Targeted interventions may be used to reduce the risk of readmission.

Immunomodulation by Mesenchymal Stromal Cells and Their Clinical Applications.

Mesenchymal stromal cells (MSCs) are multipotent progenitor cells that can be isolated and expanded from various sources. MSCs modulate the function of immune cells, including T and B lymphocytes, dendritic cells, and natural killer cells. An understanding of the interaction between MSCs and the inflammatory microenvironment will provide critical information in revealing the precise in vivo mechanisms involved in MSCs-mediated therapeutic effects, and for designing more practical protocols for the clinical use of these cells. In this review we describe the current knowledge of the unique biological properties of MSCs, the immunosuppressive effects on immune-competent cells and the paracrine role of soluble factors. A summary of the participation of MSCs in preclinical and clinical studies in treating autoimmune diseases and other diseases is described. We also discuss the current challenges of their use and their potential roles in cell therapies.

Outcomes following operative vs. non-operative management of blunt traumatic pancreatic injuries: a retrospective multi-institutional study.

BACKGROUND: Traumatic pancreatic injuries are rare, and guidelines specifying management are controversial and difficult to apply in the acute clinical setting. Due to sparse data on these injuries, we carried out a retrospective review to determine outcomes following surgical or non-surgical management of traumatic pancreatic injuries. We hypothesize a higher morbidity and mortality rate in patients treated surgically when compared to patients treated non-surgically. METHODS: We performed a retrospective review of data from four trauma centers in New York from 1990-2014, comparing patients who had blunt traumatic pancreatic injuries who were managed operatively to those managed non-operatively. We compared continuous variables using the Mann-Whitney U test and categorical variables using the chi-square and Fisher's exact tests. Univariate analysis was performed to determine the possible confounding factors associated with mortality in both treatment groups. RESULTS: Twenty nine patients were managed operatively and 32 non-operatively. There was a significant difference between the operative and non-operative groups in median age (37.0 vs. 16.2 years, P = 0.016), grade of pancreatic injury (grade I; 30.8 vs. 85.2%, P value for all comparisons <0.0001), median injury severity score (ISS) (16.0 vs. 4.0, P = 0.002), blood transfusion (55.2 vs. 15.6%, P = 0.0012), other abdominal injuries (79.3 vs. 38.7%, P = 0.0014), pelvic fractures (17.2 vs. 0.00%, P = 0.020), intensive care unit (ICU) admission (86.2 vs. 50.0%, P = 0.003), median length of stay (LOS) (16.0 vs. 4.0 days, P <0.0001), and mortality (27.6 vs. 3.1%, P = 0.010). CONCLUSIONS: Patients with traumatic pancreatic injuries treated operatively were more severely injured and suffered greater complications than those treated non-operatively. The greater morbidity and mortality associated with these patients warrants further study to determine optimal triage strategies and which subset of patients is likely to benefit from surgery.

Glycated Hemoglobin, Plasma Glucose, and Erythrocyte Aging.

BACKGROUND: The relationship between HbA1c and blood glucose averages has been characterized many times, yet, a unifying, mechanistic description is still lacking. METHODS: We calculated the level of HbA1c from plasma glucose averages based solely on the in vivo rate of hemoglobin glycation, and the different turnover rates for erythrocytes of different ages. These calculations were then compared to the measured change of HbA1c due to changes in mean blood glucose (MBG), to complex models in the literature, and our own experiments. RESULTS: Analysis of data on erythrocyte ageing patterns revealed that 2 separate RBC turnover mechanisms seem to be present. We calculated the mean red blood cell (RBC) life span within individuals to lie between 60 and 95 days. Comparison of expected HbA1c levels to data taken from continuous glucose monitors and finger-stick MBG yielded good agreement (r = .87, P < .0001). Experiments on the change with time of HbA1c induced by a change of MBG were in excellent agreement with our calculations (r = .98, P < .0001). CONCLUSIONS: RBC turnover seems to be dominated by a constant rate of cell loss, and a mechanism that targets cells of a specific age. Average RBC life span is 80 ± 10.9 days. Of HbA1c change toward treatment goal value, 50% is reached in about 30 days. Many factors contribute to the ratio of glycated hemoglobin, yet we can make accurate estimations considering only the in vivo glycation constant, MBG, and the age distribution of erythrocytes.

Recipient Criteria Predictive of Graft Failure in Kidney Transplantation.

Several classifications systems have been developed to predict outcomes of kidney transplantation based on donor variables. This study aims to identify kidney transplant recipient variables that would predict graft outcome irrespective of donor characteristics. All U.S. kidney transplant recipients between October 25,1999 and January 1, 2007 were reviewed. Cox proportional hazards regression was used to model time until graft failure. Death-censored and nondeath-censored graft survival models were generated for recipients of live and deceased donor organs. Recipient age, gender, body mass index (BMI), presence of cardiac risk factors, peripheral vascular disease, pulmonary disease, diabetes, cerebrovascular disease, history of malignancy, hepatitis B core antibody, hepatitis C infection, dialysis status, panel-reactive antibodies (PRA), geographic region, educational level, and prior kidney transplant were evaluated in all kidney transplant recipients. Among the 88,284 adult transplant recipients the following groups had increased risk of graft failure: younger and older recipients, increasing PRA (hazard ratio [HR],1.03-1.06], increasing BMI (HR, 1.04-1.62), previous kidney transplant (HR, 1.17-1.26), dialysis at the time of transplantation (HR, 1.39-1.51), hepatitis C infection (HR, 1.41-1.63), and educational level (HR, 1.05-1.42). Predictive criteria based on recipient characteristics could guide organ allocation, risk stratification, and patient expectations in planning kidney transplantation.

Steroid maintenance is associated with an increased risk of infections but has no effect on patient and graft survival in pancreas transplantation: A retrospective review of the UNOS database.

INTRODUCTION: The appropriateness of steroid maintenance in pancreas transplantation is unproven. The current literature is insufficient due to small numbers, short follow-up and sparse data. METHODS: Data from the UNOS database on adults ≥18 years old, who received pancreas and kidney-pancreas transplants between January 1996 and March 2014 were analyzed (n = 27,077). Two groups were evaluated: (a) Steroids Induction only (n = 4391) and (b) Steroid maintenance (n = 22,686). One-, 3-, 5-, 10-, and 15-year unadjusted patient and graft survival rates were compared. A Cox proportional hazards model was used to determine what patient factors were associated with these outcomes. RESULTS: There were differences in patient survival at 1 and 3 years and in graft survival at 3 and 5 years. There was a higher rate of infectious complications in the maintenance group, but after controlling for several recipient factors, whether a patient received steroid maintenance or not, was not significantly associated with the risk of death or graft failure. CONCLUSION: The use of maintenance steroids is significantly associated with an increased risk of infectious complications, but no difference in patient death or graft failure after controlling for multiple recipient factors. There is also no benefit with the use of steroid maintenance after pancreas transplantation.

Adenocarcinoma arising at ileostomy sites: Two cases and a review of the literature.

Total colectomy with ileostomy placement is a treatment for patients with inflammatory bowel disease or familial adenomatous polyposis (FAP). A rare and late complication of this treatment is carcinoma arising at the ileostomy site. We describe two such cases: a 78-year-old male 30 years after subtotal colectomy and ileostomy for FAP, and an 85-year-old male 50 years after colectomy and ileostomy for ulcerative colitis. The long latency period between creation of the ileostomies and development of carcinoma suggests a chronic metaplasia due to an irritating/inflammatory causative factor. Surgical excision of the mass and relocation of the stoma is the mainstay of therapy, with possible benefits from adjuvant chemotherapy. Newly developed lesions at stoma sites should be biopsied to rule out the possibility of this rare ileostomy complication.

Geographic inequities in liver allograft supply and demand: does it affect patient outcomes?

BACKGROUND: Significant geographic inequities mar the distribution of liver allografts for transplantation. METHODS: We analyzed the effect of geographic inequities on patient outcomes. During our study period (January 1 through December 31, 2010), 11,244 adult candidates were listed for liver transplantation: 5,285 adult liver allografts became available, and 5,471 adult recipients underwent transplantation. We obtained population data from the 2010 United States Census. To determine the effect of regional supply and demand disparities on patient outcomes, we performed linear regression and multivariate Cox regression analyses. RESULTS: Our proposed disparity metric, the ratio of listed candidates to liver allografts available varied from 1.3 (region 11) to 3.4 (region 1). When that ratio was used as the explanatory variable, the R(2) values for outcome measures were as follows: 1-year waitlist mortality, 0.23 and 1-year posttransplant survival, 0.27. According to our multivariate analysis, the ratio of listed candidates to liver allografts available had a significant effect on waitlist survival (hazards ratio, 1.21; 95% confidence interval, 1.04-1.40) but was not a significant risk factor for posttransplant survival. CONCLUSION: We found significant differences in liver allograft supply and demand--but these differences had only a modest effect on patient outcomes. Redistricting and allocation-sharing schemes should seek to equalize regional supply and demand rather than attempting to equalize patient outcomes.

Continuous glucose monitoring analysis as predictor of islet yield and insulin requirements in autologous islet transplantation after complete pancreatectomy.

We analyzed the pretransplant continuous glucose monitoring (CGM) data of 45 patients that underwent total pancreatectomy followed by autologous islet transplantation (AIT) at the University of Arizona Medical Center. Traditional and novel metrics of CGM time series were correlated to the total islet count (TIC), islet equivalents (IEQs), and weight-normalized IEQs (IEQ/kg). In a subset cohort (n = 26) we analyzed the relationship among the infused number of islets, the CGM indicators, and the first recorded insulin requirement after the procedure. We conclude that receiving a high islet yield is sufficient yet not necessary to achieve low or null insulin requirements within the first 50 days after surgery. Furthermore, CGM inertia and CGM length of curve (2 novel CGM indicators) are shown to be correlated to islet yield, and the CGMs normalized area (Ao) and time ratio above hyperglycemic level (To) are strongly correlated to insulin requirement. A screening test based on To is shown to have 100% sensitivity and 88% specificity discriminating insulin independence upon discharge.

Long-term outcomes after total pancreatectomy and islet cell autotransplantation: is it a durable operation?

OBJECTIVE: Total pancreatectomy and islet cell autotransplantation (TPIAT) has been increasingly utilized for the management of chronic pancreatitis (CP) with early success. However, the long-term durability of this operation remains unclear. METHODS: All patients undergoing TPIAT for the treatment of CP with 5-year or greater follow-up were identified for inclusion in this single-center observational study. End points included narcotic requirements, glycemic control, islet function, quality of life (QOL), and survival. RESULTS: Between 2000 and 2013, 166 patients underwent TPIAT; 112 of these patients had 5-year follow-up data to analyze. All patients underwent successful IAT with a mean of 6027 ± 595 islet equivalents per body weight. There was no perioperative mortality and actuarial survival at 5 years was 94.6%. The narcotic independence rate at 1 year was 55% and continued to improve to 73% at 5-year follow-up (P < 0.05). The insulin independence rate declined over time (38% at 1 year vs 27% at more than 5 years), but insulin requirements remained similar (21.4 vs 24.3 units per day, P = 0.6). All patients achieved stable glycemic control with a median hemoglobin A1C (HgA1C) of 6.9% (range: 5.85%-8.3%). The short form 36-item QOL assessment of a subset of patients available for contact demonstrated continued improvements in all tested modules in patients with at least 5-year follow-up. Two patients developed diabetic complications requiring whole organ pancreas transplant for salvage. CONCLUSIONS: This represents one of the largest series examining long-term outcomes after TPIAT. This operation produces durable pain relief and improvement in QOL parameters. Insulin independence rates decline over time, but most patients maintain stable glycemic control.

Scaffold architecture controls insulinoma clustering, viability, and insulin production.

Recently, in vitro diagnostic tools have shifted focus toward personalized medicine by incorporating patient cells into traditional test beds. These cell-based platforms commonly utilize two-dimensional substrates that lack the ability to support three-dimensional cell structures seen in vivo. As monolayer cell cultures have previously been shown to function differently than cells in vivo, the results of such in vitro tests may not accurately reflect cell response in vivo. It is therefore of interest to determine the relationships between substrate architecture, cell structure, and cell function in 3D cell-based platforms. To investigate the effect of substrate architecture on insulinoma organization and function, insulinomas were seeded onto 2D gelatin substrates and 3D fibrous gelatin scaffolds with three distinct fiber diameters and fiber densities. Cell viability and clustering was assessed at culture days 3, 5, and 7 with baseline insulin secretion and glucose-stimulated insulin production measured at day 7. Small, closely spaced gelatin fibers promoted the formation of large, rounded insulinoma clusters, whereas monolayer organization and large fibers prevented cell clustering and reduced glucose-stimulated insulin production. Taken together, these data show that scaffold properties can be used to control the organization and function of insulin-producing cells and may be useful as a 3D test bed for diabetes drug development.