Islet graft function by mixed meal tolerance testing is sustained over 4 years in young children undergoing total pancreatectomy with islet autotransplantation.

Children with intractable chronic pancreatitis may require total pancreatectomy with islet autotransplantation (TPIAT) for pain relief. The IAT reduces the severity of post- pancreatectomy diabetes. We analyzed 635 mixed meal tolerance tests (MMTT) in 134 children undergoing TPIAT to determine whether superior survival of islet grafts explains higher rates of insulin independence previously reported in young children (n = 52, age 3-11 years) versus adolescents (n = 82, age 12-18 years). For MMTT, children consumed Boost HP and we sampled C-peptide and glucose repeatedly over 2 h. The trajectory of outcomes before and after TPIAT was compared between children and adolescents using data from pre-TPIAT and 3, 6 months, 1, 2, 3, and 4 years post-TPIAT and mixed linear models with a random effect for child. Cox regression was used to analyze time outcomes (e.g., time to first off insulin). Islet mass transplanted, measured as islet equivalents (IEQ), was higher in adolescents (p = .003) but IEQ/kg was higher in young children (p < .001) because of their lower weight. AUC C-peptide in young children increased somewhat over 4 years, but was stable in adolescents (p = .0013). AUC glucose increased more in adolescents over time post-TPIAT (p = .0024). Islet function by AUC C-peptide:AUC glucose ratio was better preserved in young children (p < .001). Adolescents were less likely to wean off insulin (hazard ratio .44 [95% CI .28, .69]). These data support an advantage of young age in islet graft survival after TPIAT. The greater likelihood of insulin independence in young children may be driven by better islet survival after transplant.

A realist evaluation of a multifactorial falls prevention programme in care homes.

BACKGROUND: falls in care homes are common, costly and hard to prevent.Multifactorial falls programmes demonstrate clinical and cost-effectiveness, but the heterogeneity of the care home sector is a barrier to their implementation. A fuller appreciation of the relationship between care home context and falls programme delivery will guide development and support implementation. METHODS: this is a multi-method process evaluation informed by a realist approach.Data include fidelity observations, stakeholder interviews, focus groups, documentary review and falls-rate data. Thematic analysis of qualitative data and descriptive statistics are synthesised to generate care home case studies. RESULTS: data were collected in six care homes where a falls programme was trialled. Forty-four interviews and 11 focus groups complemented observations and document review.The impact of the programme varied. Five factors were identified: (i) prior practice and (ii) training may inhibit new ways of working; (iii) some staff may be reluctant to take responsibility for falls; (iv) some may feel that residents living with dementia cannot be prevented from falling; and, (v) changes to management may disturb local innovation.In some care homes, training and improved awareness generated a reduction in falls without formal assessments being carried out. CONCLUSIONS: different aspects of the falls programme sparked different mechanisms in different settings, with differing impact upon falls.The evaluation has shown that elements of a multifactorial falls programme can work independently of each other and that it is the local context (and local challenges faced), which should shape how a falls programme is implemented.

Progress in individualizing autologous islet isolation techniques for pediatric islet autotransplantation after total pancreatectomy in children for chronic pancreatitis.

Total pancreatectomy with islet autotransplantation is performed to treat chronic pancreatitis in children. Successful islet isolation must address the challenges of severe pancreatic fibrosis and young donor age. We have progressively introduced modifications to optimize enzymatic and mechanical dissociation of the pancreas during islet isolation. We evaluated 2 islet isolation metrics in 138 children-digest islet equivalents per gram pancreas tissue (IEQ/g) and digest IEQ per kilogram body weight (IEQ/kg), using multiple regression to adjust for key disease and patient features. Islet yield at digest had an average 4569 (standard deviation 2949) islet equivalent (IEQ)/g and 4946 (4009) IEQ/kg, with 59.1% embedded in exocrine tissue. Cases with very low yield (<2000 IEQ/g or IEQ/kg) have decreased substantially over time, 6.8% and 9.1%, respectively, in the most recent tertile of time compared to 19.2% and 23.4% in the middle and 34.1% and 36.4% in the oldest tertile. IEQ/g and IEQ/kg adjusted for patient and disease factors improved in consistency and yield in the modern era. Minimal mechanical disruption during digestion, warm enzymatic digestion using enzyme collagenase:NP activity ratio < 10:1, coupled with extended distension and trimming time during islet isolation of younger and fibrotic pediatric pancreases, gave increased islet yield with improved patient outcomes.

Learning from a successful process evaluation in care homes.

INTRODUCTION: process evaluations (PE) are increasingly used in parallel with randomised controlled trials (RCT) to inform the implementation of complex health interventions. This paper explores the learning accrued from conducting a PE within the Falls in Care Homes Study (FinCH), a large UK RCT. METHODS: in the FinCH study, six purposively sampled care homes provided data for the PE, which followed a realist approach. In this study researchers kept written diaries of their experiences in completing the interviews, focus groups and observations. We have reflected on these and present the main themes for discussion. FINDINGS: care home staff were enthusiastic to participate in the PE but researchers found it difficult to collect data due to staff not having time to take part, environmental factors such as no space for focus groups and low levels of research understanding. Researchers found that the expectations of the PE protocol were often unrealistic due to these limitations. Flexible and pragmatic approaches such as interviews in place of focus groups enabled data collection but required a reduced sample size and length of data collection to be accepted by researchers. CONCLUSION: to enable care home staff to participate in successful PEs, researchers should build flexibility into research schedules, spend time building trust, collaborate with all levels of care home staff prior to data collection, increase research capacity in care home staff and co-design research projects.

Community clinicians' views about patient adherence to osteoporosis medication.

Anecdotal and research evidence suggests that poor adherence and persistence with oral bisphosphonates can result in patients being at increased risk of osteoporotic fractures. Several interventions have been researched for their effectiveness with adherence and persistence, but the most effective method of supporting patients with oral bisphosphonate medications is clinician reviews, generally identified as doctors and nurses. This service evaluation aimed to explore the knowledge and views of multidisciplinary community-based clinicians about adherence and persistence with oral bisphosphonates. The results indicated a positive attitude to a multidisciplinary approach supporting patients to take their medication as prescribed, with recommendations for future research.

Total Pancreatectomy With Islet Autotransplantation Resolves Pain in Young Children With Severe Chronic Pancreatitis.

OBJECTIVES: Fear of diabetes and major surgery may prohibit referral of young children severely affected by pancreatitis for total pancreatectomy with islet autotransplant (TPIAT). We evaluated outcomes in our youngest TPIAT recipients, 3 to 8 years of age at surgery. METHODS: Medical records were reviewed for 17 children (9 girls) ages 8 years or younger undergoing TPIAT from 2000 to 2014. Most (14/17) had genetic risk factors for pancreatitis. Since 2006, TPIAT recipients were followed prospectively with health questionnaires including assessments of pain and narcotic use, and scheduled hemoglobin A1c (HbA1c) and mixed-meal tolerance tests (6 mL/kg Boost HP) before surgery, and at regular intervals after. Patients are 1 to 11 years post-TPIAT (median 2.2 years). Data are reported as median (25th, 75th percentile). RESULTS: All had relief of pain, with all 17 patients off narcotics at most recent follow-up. Hospitalization rates decreased from 5.0 hospitalization episodes per person-year of follow-up before TPIAT, to 0.35 episodes per person-year of follow-up after TPIAT. Fourteen (82%) discontinued insulin, higher than the observed insulin independence rate of 41% in 399 patients older than 8 years of age undergoing TPIAT over the same interval (P = 0.004). Median post-TPIAT HbA1c was 5.9% (5.6%, 6.3%), and within patient post-TPIAT mean HbA1c was ≤6.5% for all but 2 patients. CONCLUSIONS: Young children with severe refractory chronic pancreatitis may be good candidates for TPIAT, with high rates of pain relief and insulin independence, and excellent glycemic control in the majority.

Factors Predicting Outcomes After a Total Pancreatectomy and Islet Autotransplantation Lessons Learned From Over 500 Cases.

OBJECTIVE: Our objective was to analyze factors predicting outcomes after a total pancreatectomy and islet autotransplantation (TP-IAT). BACKGROUND: Chronic pancreatitis (CP) is increasingly treated by a TP-IAT. Postoperative outcomes are generally favorable, but a minority of patients fare poorly. METHODS: In our single-centered study, we analyzed the records of 581 patients with CP who underwent a TP-IAT. Endpoints included persistent postoperative "pancreatic pain" similar to preoperative levels, narcotic use for any reason, and islet graft failure at 1 year. RESULTS: In our patients, the duration (mean ±â€ŠSD) of CP before their TP-IAT was 7.1 ±â€Š0.3 years and narcotic usage of 3.3 ±â€Š0.2 years. Pediatric patients had better postoperative outcomes. Among adult patients, the odds of narcotic use at 1 year were increased by previous endoscopic retrograde cholangiopancreatography (ERCP) and stent placement, and a high number of previous stents (>3). Independent risk factors for pancreatic pain at 1 year were pancreas divisum, previous body mass index >30, and a high number of previous stents (>3). The strongest independent risk factor for islet graft failure was a low islet yield-in islet equivalents (IEQ)-per kilogram of body weight. We noted a strong dose-response relationship between the lowest-yield category (<2000 IEQ) and the highest (≥5000 IEQ or more). Islet graft failure was 25-fold more likely in the lowest-yield category. CONCLUSIONS: This article represents the largest study of factors predicting outcomes after a TP-IAT. Preoperatively, the patient subgroups we identified warrant further attention.

Pediatric Autologous Islet Transplantation.

A total pancreatectomy and islet autotransplant (TPIAT) offers substantial pain relief and improved quality of life for children who are severely affected by chronic or recurrent acute pancreatitis and for whom the usual medical and endoscopic therapies have failed. The pancreas is entirely resected, and the pancreatic islets are isolated from the pancreas and infused back into the patient's liver. Because this is an autologous transplant, no immunosuppression is required. Over several months, the islets engraft in the liver; the patient is then slowly weaned off insulin therapy. Slightly more than 40 % of patients become and remain insulin independent, yet even among patients who remain on insulin, most have some islet function, permitting easier diabetes control. The majority of patients experience pain relief, with significant improvements in health-related quality of life. A TPIAT should be considered for children who are significantly disabled by chronic pancreatitis.

Total pancreatectomy and islet autotransplantation in children for chronic pancreatitis: indication, surgical techniques, postoperative management, and long-term outcomes.

OBJECTIVE: Describe the surgical technique, complications, and long-term outcomes of total pancreatectomy and islet autotransplantation (TP-IAT) in a large series of pediatric patients. BACKGROUND: Surgical management of childhood pancreatitis is not clear; partial resection or drainage procedures often provide transient pain relief, but long-term recurrence is common due to the diffuse involvement of the pancreas. Total pancreatectomy (TP) removes the source of the pain, whereas islet autotransplantation (IAT) potentially can prevent or minimize TP-related diabetes. METHODS: Retrospective review of 75 children undergoing TP-IAT for chronic pancreatitis who had failed medical, endoscopic, or surgical treatment between 1989 and 2012. RESULTS: Pancreatitis pain and the severity of pain statistically improved in 90% of patients after TP-IAT (P < 0.001). The relief from narcotics was sustained. Of the 75 patients undergoing TP-IAT, 31 (41.3%) achieved insulin independence. Younger age (P = 0.032), lack of prior Puestow procedure (P = 0.018), lower body surface area (P = 0.048), higher islet equivalents (IEQ) per kilogram body weight (P = 0.001), and total IEQ (100,000) (P = 0.004) were associated with insulin independence. By multivariate analysis, 3 factors were associated with insulin independence after TP-IAT: (1) male sex, (2) lower body surface area, and (3) higher total IEQ per kilogram body weight. Total IEQ (100,000) was the single factor most strongly associated with insulin independence (odds ratio = 2.62; P < 0.001). CONCLUSIONS: Total pancreatectomy and islet autotransplantation provides sustained pain relief and improved quality of life. The ß-cell function is dependent on islet yield. Total pancreatectomy and islet autotransplantation is an effective therapy for children with painful pancreatitis that failed medical and/or endoscopic management.

Total pancreatectomy and islet autotransplantation in chronic pancreatitis: recommendations from PancreasFest.

DESCRIPTION: Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure used to treat severe complications of chronic pancreatitis or very high risk of pancreatic cancer while reducing the risk of severe diabetes mellitus. However, clear guidance on indications, contraindications, evaluation, timing, and follow-up are lacking. METHODS: A working group reviewed the medical, psychological, and surgical options and supporting literature related to TPIAT for a consensus meeting during PancreasFest. RESULTS: Five major areas requiring clinical evaluation and management were addressed: These included: 1) indications for TPIAT; 2) contraindications for TPIAT; 3) optimal timing of the procedure; 4) need for a multi-disciplinary team and the roles of the members; 5) life-long management issues following TPIAP including diabetes monitoring and nutrition evaluation. CONCLUSIONS: TPIAT is an effective method of managing the disabling complications of chronic pancreatitis and risk of pancreatic cancer in very high risk patients. Careful evaluation and long-term management of candidate patients by qualified multidisciplinary teams is required. Multiple recommendations for further research were also identified.

Systematic intraoperative cholangiography during elective laparoscopic cholecystectomy: Is it a justifiable practice?

Backgrounds/Aims: Routine execution of intraoperative cholangiography (IOC) in laparoscopic cholecystectomy (LC) is considered a good practice to help early identification of biliary duct injuries (BDIs) or common bile duct (CBD) stones. This study aimed to determine the impact of IOC during LC. Methods: This is a retrospective, monocentric study, including patients with a LC performed from January 2020 to December 2021. Results: Of 303 patients, 215 (71.0%) were in the IOC group and 88 (29.0%) in the no-IOC group. IOC was incomplete or unclear in 10.7% of patients, with a failure rate of 14.7%. Operating time was 15 minutes longer in the IOC group (p = 0.01), and postoperative complications were higher (5.1% vs. 0.0%, p = 0.03). There were three BDIs (0.99%), all included in the IOC group; only one was diagnosed intraoperatively, and the other two were identified during the postoperative course. Regarding identifying CBD stones, IOC showed a sensitivity of 77%, a specificity of 98%, an accuracy of 97.2%, a positive predictive value of 63% and a negative predictive value of 99%. Conclusions: Systematic IOC has shown no specific benefits and prolonged operative duration. IOC should be performed on selected patients or in situations of uncertainty on the anatomy.

Posterior urethral valve treatments and outcomes in children receiving kidney transplants.

PURPOSE: We evaluated the impact of surgical approaches to posterior urethral valves on renal transplant survival and compared transplant survival in children with vs without posterior urethral valves. MATERIALS AND METHODS: We reviewed the records of all children who underwent renal transplantation from January 1984 to March 2008 and performed univariate subgroup analysis in those with posterior urethral valves. We evaluated the ureteroneocystotomy method, immunosuppression and valve treatment. In patients with posterior urethral valves we regarded nocturnal and/or daytime incontinence, severe urgency and the need for intermittent catheterization or double voiding for increased post-void residual urine as signs of bladder dysfunction. RESULTS: The initial renal transplant was received by 418 children at a mean age of 5.6 years. The 59 boys with posterior urethral valves received a total of 69 kidneys. By 8-year followup the kidney had failed in 24 of 59 boys with and 143 of 359 without posterior urethral valves (OR 0.9665, 95% CI 0.5462-1.692, p = 0.9105). Immunosuppression was consistent in the 2 groups. Outcomes were similar across all ureteroneocystotomy techniques. Initial management for posterior urethral valves was valve ablation alone in 12 boys, vesicostomy in 7 and supravesical diversion in 11. There was no difference in transplant survival or bladder dysfunction based on valve intervention. In 18 boys (55%) we noted overlapping signs of bladder dysfunction, of whom 11 performed intermittent catheterization or had increased post-void residual urine, 4 had severe urgency, 4 had daytime incontinence and 7 had nocturnal incontinence. Bladder dysfunction did not predict increased graft loss (OR 3.306, 95% CI 0.7615-16.27, p = 0.1134). CONCLUSIONS: Of children who undergo renal transplantation boys with posterior urethral valves do not have a higher graft failure rate. Treatment for posterior urethral valves did not significantly impact transplant survival or bladder dysfunction.

Evaluation of the pituitary function with insulin tolerance (hypoglycaemia) testing: are there any differences using insulin lispro compared to regular insulin?

BACKGROUND/AIM: The insulin tolerance test (ITT) remains the gold standard for evaluating the pituitary function, but has potential risks when hypoglycaemia is induced. There are scarce data using short-acting insulin analogs for ITTs. This pilot study compares the effects of insulin lispro (LPI) with regular insulin (RGI) during an ITT. METHODS: Patients with suspected hypopituitarism (n = 103) randomly received either LPI (n = 51) or RGI (n = 52). RESULTS: All patients reported signs and symptoms when hypoglycaemia was induced. In the LPI group, hypoglycaemia occurred sooner (23.6 +/- 1.6 vs. 28.3 +/- 1.4 min, p < 0.05), and duration of hypoglycaemia (25.0 +/- 1.7 vs. 31.9 +/- 1.9 min, p < 0.05) and time for blood glucose levels to return to a 'safe' level (>3.3 mmol/l; 56.5 +/- 2.3 vs. 76.0 +/- 2.1 min, p < 0.001) were shorter as compared with the RGI group. No differences in peak growth hormone and cortisol levels were observed between the two groups. CONCLUSIONS: Our data suggest that despite inducing similar symptomatology, LPI exerted a quicker onset and a shorter duration of hypoglycaemia as compared with RGI. Thus, using LPI might reduce the potential risks associated with an ITT by shortening the hypoglycaemic phase of the test.

Improved Outcomes of Kidney Transplantation in Infants (Age < 2 years): A Single-Center Experience.

BACKGROUND: Infants (age, < 2 years) with end-stage renal disease (ESRD) have increased morbidity and mortality. We evaluated our long-term outcomes of kidney transplants (KTx) in infants. METHODS: Between 1984 and 2014, 136 infants underwent KTx. We examined trends in survival rates and complications by era (1984-1993 [era 1], 1994-2003 [era 2], 2004-2014 [era 3]). RESULTS: Patients were 92.6% white and 70.6% males. Posttransplant (Tx) initial length of hospital stay declined 37% over the 30-year period (P <0.01). Ten-year death-censored graft survival improved from 60% (era 1) to 80% (era 2) (P = 0.04). The incidence of acute rejection, graft thrombosis, cytomegalovirus, and urine leaks did not significantly change across eras. Frequency of Epstein-Barr virus diagnosis (era 2 vs era 3, P < 0.01) increased. Post-Tx lymphoproliferative disorder incidence was increased in era 2 compared with eras 1 and 3 (P = 0.03). CONCLUSIONS: Infants deserve earlier consideration for KTx. Length of initial hospital stay and patient and graft survival rates after KTx have improved in infants since 1984.

Is further evaluation for growth hormone (GH) deficiency necessary in fibromyalgia patients with low serum insulin-like growth factor (IGF)-I levels?

OBJECTIVE: Fibromyalgia (FM) is characterized by diffuse pain, fatigue, and sleep disturbances; symptoms that resemble the adult growth hormone (GH) deficiency syndrome. Many FM patients have low serum GH levels, with a hypothesized aetiology of dysregulated GH/insulin-like growth factor (IGF)-I axis. The aim of this study was to assess the GH reserve in FM patients with low serum IGF-I levels using the GH-releasing hormone (GHRH)-arginine test. DESIGN: We retrospectively reviewed the GHRH-arginine data of 77 FM patients with low serum IGF-I levels referred to our tertiary unit over a 4-year period. RESULTS: Of the 77 FM patients, 13 patients (17%) failed the GHRH-arginine test. Further evaluation with pituitary imaging revealed normal pituitary glands (n=7), coincident microadenomas (n=4), empty sella (n=1) and pituitary cyst (n=1), and relevant medical histories such as previous head injury (n=4), Sheehan's syndrome (n=1), and whiplash injury (n=1). In contrast, the remaining 64 patients (83%) that responded to the GHRH-arginine test demonstrated higher peak GH levels compared to age and BMI-matched controls (n=24). CONCLUSION: Our data shows that a subpopulation of FM patients with low serum IGF-I levels will fail the GHRH-arginine test. We, thus, recommend that the GH reserve of these patients should be evaluated further, as GH replacement may potentially improve the symptomatology of those with true GH deficiency. Additionally, the increased GH response rates to GHRH-arginine stimulation in the majority of FM patients with low serum IGF-I levels further supports the hypothesis of a dysregulated GH/IGF-I axis in the pathophysiology of FM.

Thymoglobulin versus ATGAM induction therapy in pediatric kidney transplant recipients: a single-center report.

BACKGROUND: Induction immunosuppressive therapy with the anti-T-cell antibody Thymoglobulin decreases the incidence of acute rejection in adult kidney transplant (KTx) recipients, but limited data are available for pediatric KTx recipients. METHODS: We conducted a historical cohort study to compare rates of survival, rejection, and infection in pediatric (age <19 years) KTx recipients who received induction therapy with polyclonal antibody, ATGAM (n=127) or Thymoglobulin (n=71), from December 1, 1992, to January 31, 2003. Maintenance immunosuppression included cyclosporine, azathioprine or mycophenolate mofetil, and prednisone. Mean follow-up was 90+/-25 months for ATGAM recipients and 32+/-15 months for Thymoglobulin recipients. RESULTS: Overall, the incidence of acute rejection was lower in Thymoglobulin recipients versus ATGAM recipients (33% vs. 50%, P=0.02). Epstein-Barr virus (EBV) infection was higher in Thymoglobulin recipients versus ATGAM recipients (8% vs. 3%, P=0.002). But the two groups did not significantly differ in patient and graft survival rates, incidence of chronic rejection, EBV lymphoma, or other infection. CONCLUSIONS: Thus, Thymoglobulin induction was associated with a decreased incidence of acute rejection and an increased incidence of EBV infection in pediatric KTx recipients. EBV monitoring should be performed in EBV-naive recipients receiving Thymoglobulin.

Urolithiasis after kidney transplantation in pediatric recipients: a single center report.

BACKGROUND: Urolithiasis occurs in approximately 6% of adult kidney transplant (KTx) recipients. Limited data are available on urolithiasis after pediatric KTx. We report the incidence, management of, and risk factors for stone development in children after KTx. METHODS: We reviewed the medical records of 399 children who received KTx at our center between September 1986 and January 2003. Transplant outcomes were compared in stone formers and controls. RESULTS: Twenty (5%) patients, age 9+/-5 (X +/- SD) years, developed stones over the follow-up period (74+/-53 months). Time to stone presentation was 19+/-22 months post-KTx. Presenting features were urinary tract infection (UTI), 8; gross hematuria, 5; microscopic hematuria, 2; dysuria without infection, 6; difficulty voiding, 3; and silent stones, 2. Stones were removed by cystoscopy in 11 (55%) patients. Stone composition was determined in 11 patients: calcium phosphate (55%), calcium oxalate (18%), mixed calcium phosphate and oxalate (9%), and struvite (18%). Factors predisposing to stones in study patients included suture retention (n = 4), elevated urinary calcium excretion (n = 2), recurrent UTI (n = 2), and urinary stasis (n = 2). The incidence of UTI was higher (P = 0.003) and of acute rejection was lower (P = 0.02) in stone patients compared with controls. Patient and graft survival rates and the incidence of chronic rejection did not significantly differ between study patients and controls (P = NS). CONCLUSIONS: Urolithiasis is not uncommon in pediatric KTx patients. Factors associated with post-KTx urolithiasis include retention of suture material, recurrent UTI, hypercalciuria, and urinary stasis. Treatment is associated with excellent outcome and low recurrence rate.

The stressors and demands of peacekeeping in Kosovo: predictors of mental health response.

U.S. soldiers' appraisal and experience of the Kosovo peacekeeping mission is described. Using a prospective design, we evaluated the prevalence, severity, and predictors of several mental health outcomes at redeployment. We found that peacekeepers frequently were exposed to potentially traumatizing and other stressful events while in Kosovo, but on average, their appraisal of those events was moderate. Postdeployment psychopathology was also low--soldiers endorsed more severe mental health difficulties at predeployment, which suggests anticipatory negative affect. After controlling for the impact of predeployment stressors, we examined the contribution of potentially traumatizing events, general overseas military duty stressors, negative aspects of peacekeeping roles, and generic positive military experiences, including morale, to explain variance in four outcomes: post-traumatic stress disorder, depression, hostility and aggression problems, and problems with alcohol abuse. Findings indicate that hostility and drinking may be more chronic problems that emerge during stressful times, whereas depression and post-traumatic stress disorder symptoms may be more apt to fluctuate and are associated with potentially traumatizing experiences during peacekeeping. The implications and limitations of the study are discussed.

Near-euglycemia can be achieved safely in pediatric total pancreatectomy islet autotransplant recipients using an adapted intravenous insulin infusion protocol.

BACKGROUND: Children with severe chronic pancreatitis may undergo total pancreatectomy with islet autotransplantation (TPIAT) to relieve pain while minimizing the risk of postsurgical diabetes. Because overstimulation of transplanted islets by hyperglycemia can result in ß-cell loss, we developed a specialized intravenous insulin infusion protocol (IIP) for pediatric TPIAT recipients to maintain euglycemia or near-euglycemia posttransplant. SUBJECTS AND METHODS: Our objective was to review glucose control using an IIP specific for TPIAT recipients at a single institution. We reviewed postoperative blood glucose (BG) levels for 32 children 4-18 years old with chronic pancreatitis who underwent TPIAT between July 2011 and June 2013. We analyzed the proportion of BG values in the range of 70-140 mg/dL, mean glucose, glucose variability, and occurrence of hypoglycemia during the IIP; we also evaluated the transition to subcutaneous therapy (first 72 h with multiple daily injections [MDI]). RESULTS: During IIP, the mean patient BG level was 116±27 mg/dL, with 83.1% of all values in the range of 70-140 mg/dL. Hypoglycemia was rare, with only 2.5% of values <70 mg/dL. The more recent era (n=16) had a lower mean BG and less variability than the early era (first 16 patients) (P≤0.004). Mean glucose level (116 vs. 128 mg/dL) and glucose variability were significantly lower during the IIP compared with MDI therapy (P<0.0001). CONCLUSIONS: Tight glycemic control without excessive severe hypoglycemia was achieved in children undergoing TPIAT using an IIP specifically designed for this population; the ability to maintain BG in target range improved with experience with the protocol.

Individual igf-I responsiveness to a fixed regimen of low-dose growth hormone replacement is increased with less variability in obese compared to non-obese adults with severe growth hormone deficiency.

BACKGROUND/AIMS: Decreased GH and IGF-I levels and increased GH responsiveness are frequently reported in obesity. As GH-deficient adults are commonly obese, the role of obesity in affecting hepatic responsiveness of IGF-I generation to GH stimulation is unclear in severe GH-deficient states. To address this question, we challenged a cohort of severely GH-deficient non-obese and obese adults with a fixed low GH dose (0.2 mg/day), and examined the relationship of body mass index (BMI) with IGF-I response. METHODS: 12 non-obese (6 males, median BMI 24.7 kg/m2) and 14 obese (7 males, median BMI 45.2 kg/m2) adults with severe GH deficiency were studied for 8 weeks. Blood samples were collected at baseline, and weeks 4 and 8. RESULTS: There was a larger increment and reduced variability of IGF-I levels in obese compared to non-obese GH-deficient adults at week 8, but not at week 4. A similar but smaller increment and less variability was observed with IGFBP-3. Increment IGF-I positively correlated with baseline BMI at weeks 4 (r=0.49, p<0.02) and 8 (r=0.47, p<0.02). No gender differences were observed with the IGF-I and IGFBP-3 response. CONCLUSIONS: This study demonstrates that there is a larger increment and deceased individual variability of IGF-I to the low GH replacement dose in obese compared to non-obese adults with severe GH deficiency, regardless of gender. The positive association of IGF-I increment with BMI implies a greater impact of obesity rather than GH deficiency in enhancing hepatic sensitivity to GH. These findings, thus, question the reliability of interpreting single serum IGF-I levels in non-obese adults with severe GH deficiency treated with low GH replacement doses.