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 ± SD) of CP before their TP-IAT was 7.1 ± 0.3 years and narcotic usage of 3.3 ± 0.2 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.
We aim to describe the Australian child and adolescent mental health system, which has its historical origins in the child guidance clinic, with recent efforts at modernisation to meet community ...needs and major policy innovations, including the National Disability Insurance Scheme (NDIS) and expansion of digital/telehealth services. Shared funding/responsibility across commonwealth and state/territory governments has resulted in country-wide variations, allowing innovation but also introducing fragmentation and duplication. The increase in demand outstripping supply (which was exacerbated by workforce shortages resulting from the pandemic), the lack of robust evaluation, and poor service integration (which make navigation difficult for families) are ongoing challenges.
Glucose Toxicity in β-Cells: Type 2 Diabetes, Good Radicals Gone Bad, and the Glutathione Connection
R. Paul Robertson ,
Jamie Harmon ,
Phuong Oanh Tran ,
Yoshito Tanaka and
Hiroki Takahashi
From the ...Pacific Northwest Research Institute, Seattle, Washington
Abstract
Chronic exposure to hyperglycemia can lead to cellular dysfunction that may become irreversible over time, a process that
is termed glucose toxicity. Our perspective about glucose toxicity as it pertains to the pancreatic β-cell is that the characteristic
decreases in insulin synthesis and secretion are caused by decreased insulin gene expression. The responsible metabolic lesion
appears to involve a posttranscriptional defect in pancreas duodenum homeobox-1 (PDX-1) mRNA maturation. PDX-1 is a critically
important transcription factor for the insulin promoter, is absent in glucotoxic islets, and, when transfected into glucotoxic
β-cells, improves insulin promoter activity. Because reactive oxygen species are produced via oxidative phosphorylation during
anaerobic glycolysis, via the Schiff reaction during glycation, via glucose autoxidation, and via hexosamine metabolism under
supraphysiological glucose concentrations, we hypothesize that chronic oxidative stress is an important mechanism for glucose
toxicity. Support for this hypothesis is found in the observations that high glucose concentrations increase intraislet peroxide
levels, that islets contain very low levels of antioxidant enzyme activities, and that adenoviral overexpression of antioxidant
enzymes in vitro in islets, as well as exogenous treatment with antioxidants in vivo in animals, protect the islet from the
toxic effects of excessive glucose levels. Clinically, consideration of antioxidants as adjunct therapy in type 2 diabetes
is warranted because of the many reports of elevated markers of oxidative stress in patients with this disease, which is characterized
by imperfect management of glycemia, consequent chronic hyperglycemia, and relentless deterioration of β-cell function.
Footnotes
Address correspondence and reprint requests to R. Paul Robertson, Pacific Northwest Research Institute, 720 Broadway, Seattle,
WA 98122.
Received for publication 5 September 2002 and accepted in revised form 11 November 2002.
DN, dominant-negative; GCL, γ-glutamylcysteine ligase; GSH, glutathione; GSSG, oxidized GSH; GPx, GSH peroxidase; JNK; c-Jun
NH 2 -terminal kinase; PDX-1, pancreas duodenum homeobox-1; ROS, reactive oxygen species; SOD, superoxide dismutase.
DIABETES
Child and adolescent psychiatry has an opportunity to adapt alongside the advancements in medical knowledge, post-graduate training, epidemiological realities and clinical service models. Here, we ...are guided by the mental health needs of our community’s young and their families in our review of child and adolescent psychiatry training in Australia and New Zealand. We recognise that training must respond to clinical demand and service reform while ensuring a range of clinical and educational experiences to deliver expectable competencies in order to produce child and adolescent psychiatrists that meet the communities’ needs now and in the future. We argue that training programmes be subject to rigorous evaluation by embedding continuing cycles of improvement including regular review and international bench marking.
Using solar spectral irradiance measurements from the SORCE spacecraft and the F/F' technique, we have estimated the radial velocity (RV) scatter induced on the Sun by stellar activity as a function ...of wavelength. Our goal was to evaluate the potential advantages of using new near-infrared (NIR) spectrographs to search for low-mass planets around bright F, G, and K stars by beating down activity effects. Unlike M dwarfs, which have higher fluxes and therefore greater RV information content in the NIR, solar-type stars are brightest at visible wavelengths, and, based solely on information content, are better suited to traditional optical RV surveys. However, we find that the F/F' estimated RV noise induced by stellar activity is diminished by up to a factor of four in the NIR versus the visible. Observations with the upcoming future generation of NIR instruments can be a valuable addition to the search for low-mass planets around bright FGK stars in reducing the amount of stellar noise affecting RV measurements.
Abstract Description Diabetes and glucose intolerance are common complications of chronic pancreatitis, yet clinical guidance on their detection, classification, and management is lacking. Methods A ...working group reviewed the medical problems, diagnostic methods, and treatment options for chronic pancreatitis-associated diabetes for a consensus meeting at PancreasFest 2012. Results Guidance Statement 1.1 : Diabetes mellitus is common in chronic pancreatitis. While any patient with chronic pancreatitis should be monitored for development of diabetes, those with long-standing duration of disease, prior partial pancreatectomy, and early onset of calcific disease may be at higher risk. Those patients developing diabetes mellitus are likely to have co-existing pancreatic exocrine insufficiency. Guidance Statement 1.2 : Diabetes occurring secondary to chronic pancreatitis should be recognized as pancreatogenic diabetes (type 3c diabetes). Guidance Statement 2.1 : The initial evaluation should include fasting glucose and HbA1c. These tests should be repeated annually. Impairment in either fasting glucose or HbA1c requires further evaluation. Guidance Statement 2.2 : Impairment in either fasting glucose or HbA1c should be further evaluated by a standard 75 g oral glucose tolerance test. Guidance Statement 2.3 : An absent pancreatic polypeptide response to mixed-nutrient ingestion is a specific indicator of type 3c diabetes. Guidance Statement 2.4 : Assessment of pancreatic endocrine reserve, and importantly that of functional beta-cell mass, should be performed as part of the evaluation and follow-up for total pancreatectomy with islet autotransplantation (TPIAT). Guidance Statement 3 : Patients with pancreatic diabetes shall be treated with specifically tailored medical nutrition and pharmacologic therapies. Conclusions Physicians should evaluate and treat glucose intolerance in patients with pancreatitis.
Abstract
Context
Total pancreatectomy and intrahepatic islet autotransplantation (TP/IAT) is performed to alleviate severe abdominal pain, avoid narcotic use, maintain islet function, and avoid ...diabetes in patients with chronic pancreatitis. However, many TP/IAT recipients complain of postprandial hypoglycemia.
Objective
This study was designed to discover the mechanisms of this problem.
Design
Participants consumed a triple-isotope mixed meal.
Setting
This study was performed in a hospital research unit.
Participants
We studied 10 TP/IAT recipients and 10 age- and body mass index–matched control subjects. Seven of 10 recipients had a history of postprandial hypoglycemia.
Interventions
Participants were given a 1-13C-labeled mixed meal and two tracer infusions (6,6-2H2- and 6-3H-glucose).
Main Outcome Measures
Glucose kinetics and concentrations of regulatory hormones were determined.
Results
Immediately after the meal, peak glucose was elevated in recipients compared with control subjects 266 ± 20 mg/dL (14.8 ± 1.1 mmol/L) vs 185 ± 13 mg/dL (10.3 ± 0.7 mmol/L); P = 0.01. However, mean Δ glucose for TP/IAT recipients between minutes 240 and 360 postprandially was significantly lower than for control subjects (P < 0.05); six of the seven recipients with a history of hypoglycemia experienced abnormally low postprandial Δ glucose. Δ Glucagon remained unchanged (minutes 240 to 360; P = 0.58) in TP/IAT recipients despite abnormal decreases in postprandial glucose. Radioisotopic studies revealed that meal appearance, glucose disappearance, and endogenous glucose production in TP/IAT recipients were not different from control subjects.
Conclusion
Initially high glucose levels followed by hypoglycemia with an absent glucagon response is a mechanistic sequence that contributes to postprandial hypoglycemia after TP/IAT.
TP/IAT recipients consumed a triple-isotope mixed meal and experienced hypoglycemia during the latter half of a 6-hour study. The only abnormality they demonstrated was a deficient glucagon response.
The Warm Neptune GJ 3470b Has a Polar Orbit Stefànsson, Guđmundur; Mahadevan, Suvrath; Petrovich, Cristobal ...
Astrophysical journal. Letters,
06/2022, Volume:
931, Issue:
2
Journal Article
Peer reviewed
Open access
The warm Neptune GJ 3470b transits a nearby (d = 29 pc) bright slowly rotating M1.5-dwarf star. Using spectroscopic observations during two transits with the newly commissioned NEID spectrometer on ...the WIYN 3.5 m Telescope at Kitt Peak Observatory, we model the classical Rossiter–McLaughlin effect, yielding a sky-projected obliquity of λ=98 +15 −12 ˚and a v sin i = 0.85+0.27 −0.33 kms-1. Leveraging information about the rotation period and size of the host star, our analysis yields a true obliquity of ψ=95+9 −8 ◦ , revealing that GJ 3470b is on a polar orbit. Using radial velocities from HIRES, HARPS, and the Habitable-zone Planet Finder, we show that the data are compatible with a long-term radial velocity (RV) slope of 𝛾̀=-0.0022±0.0011 ms-1day-1 over a baseline of 12.9 yr. If the RV slope is due to acceleration from another companion in the system, we show that such a companion is capable of explaining the polar and mildly eccentric orbit of GJ 3470b using two different secular excitation models. The existence of an outer companion can be further constrained with additional RV observations, Gaia astrometry, and future high-contrast imaging observations. Lastly, we show that tidal heating from GJ 3470b’s mild eccentricity has most likely inflated the radius of GJ 3470b by a factor of ∼1.5–1.7, which could help account for its evaporating atmosphere.
Abstract
Barnard’s star is among the most studied stars given its proximity to the Sun. It is often considered the radial velocity (RV) standard for fully convective stars due to its RV stability and ...equatorial decl. Recently, an
M
sin
i
=
3.3
M
⊕
super-Earth planet candidate with a 233 day orbital period was announced by Ribas et al. New observations from the near-infrared Habitable-zone Planet Finder (HPF) Doppler spectrometer do not show this planetary signal. We ran a suite of experiments on both the original data and a combined original + HPF data set. These experiments include model comparisons, periodogram analyses, and sampling sensitivity, all of which show the signal at the proposed period of 233 days is transitory in nature. The power in the signal is largely contained within 211 RVs that were taken within a 1000 day span of observing. Our preferred model of the system is one that features stellar activity without a planet. We propose that the candidate planetary signal is an alias of the 145 day rotation period. This result highlights the challenge of analyzing long-term, quasi-periodic activity signals over multiyear and multi-instrument observing campaigns.
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