Hyperglycemia in Hospital: An Independent Marker of Infection, Acute Kidney Injury, and Stroke for Hospital Inpatients.

CONTEXT: Hyperglycemia in hospital inpatients without pre-existing diabetes is associated with increased mortality. However, the independent contribution of hyperglycemia to health care-associated infection (HAI), acute kidney injury (AKI), and stroke is unclear. OBJECTIVE: To investigate the relationship between hyperglycemia and adverse clinical outcomes in hospital for patients with and without diabetes. METHODS: Diabetes IN-hospital: Glucose and Outcomes (DINGO) was a 26-week (October 2019-March 2020) prospective cohort study. Clinical and glucose data were collected up to the 14th day of admission. Primary stratification was by hyperglycemia, defined as ≥2 random capillary blood glucose (BG) measurements ≥11.1 mmol/L (≥200 mg/dL). Propensity weighting for 9 clinical characteristics was performed to allow interrogation of causality. To maintain the positivity assumption, patients with HbA1c >12.0% were excluded and prehospital treatment not adjusted for. The setting was the Royal Melbourne Hospital, a quaternary referral hospital in Melbourne, Australia. Admissions with at least 2 capillary glucose values and length of stay >24 hours were eligible, with half randomly sampled. Outcome measures were HAI, AKI, stroke, and mortality. RESULTS: Of 2558 included admissions, 1147 (45%) experienced hyperglycemia in hospital. Following propensity-weighting and adjustment, hyperglycemia in hospital was found to, independently of 9 covariables, contribute an increased risk of in-hospital HAI (130 [11.3%] vs 100 [7.1%], adjusted odds ratio [aOR] 1.03, 95% CI 1.01-1.05, P = .003), AKI (120 [10.5%] vs 59 [4.2%], aOR 1.07, 95% CI 1.05-1.09, P < .001), and stroke (10 [0.9%] vs 1 [0.1%], aOR 1.05, 95% CI 1.04-1.06, P < .001). CONCLUSION: In hospital inpatients (HbA1c ≤12.0%), irrespective of diabetes status and prehospital glycemia, hyperglycemia increases the risk of in-hospital HAI, AKI, and stroke compared with those not experiencing hyperglycemia.

Baricitinib and ß-Cell Function in Patients with New-Onset Type 1 Diabetes.

BACKGROUND: Janus kinase (JAK) inhibitors, including baricitinib, block cytokine signaling and are effective disease-modifying treatments for several autoimmune diseases. Whether baricitinib preserves ß-cell function in type 1 diabetes is unclear. METHODS: In this phase 2, double-blind, randomized, placebo-controlled trial, we assigned patients with type 1 diabetes diagnosed during the previous 100 days to receive baricitinib (4 mg once per day) or matched placebo orally for 48 weeks. The primary outcome was the mean C-peptide level, determined from the area under the concentration-time curve, during a 2-hour mixed-meal tolerance test at week 48. Secondary outcomes included the change from baseline in the glycated hemoglobin level, the daily insulin dose, and measures of glycemic control assessed with the use of continuous glucose monitoring. RESULTS: A total of 91 patients received baricitinib (60 patients) or placebo (31 patients). The median of the mixed-meal-stimulated mean C-peptide level at week 48 was 0.65 nmol per liter per minute (interquartile range, 0.31 to 0.82) in the baricitinib group and 0.43 nmol per liter per minute (interquartile range, 0.13 to 0.63) in the placebo group (P = 0.001). The mean daily insulin dose at 48 weeks was 0.41 U per kilogram of body weight per day (95% confidence interval [CI], 0.35 to 0.48) in the baricitinib group and 0.52 U per kilogram per day (95% CI, 0.44 to 0.60) in the placebo group. The levels of glycated hemoglobin were similar in the two trial groups. However, the mean coefficient of variation of the glucose level at 48 weeks, as measured by continuous glucose monitoring, was 29.6% (95% CI, 27.8 to 31.3) in the baricitinib group and 33.8% (95% CI, 31.5 to 36.2) in the placebo group. The frequency and severity of adverse events were similar in the two trial groups, and no serious adverse events were attributed to baricitinib or placebo. CONCLUSIONS: In patients with type 1 diabetes of recent onset, daily treatment with baricitinib over 48 weeks appeared to preserve ß-cell function as estimated by the mixed-meal-stimulated mean C-peptide level. (Funded by JDRF International and others; BANDIT Australian New Zealand Clinical Trials Registry number, ACTRN12620000239965.).

Early intervention model of inpatient diabetes care improves glycemia following hospitalization.

Admission to hospital provides an opportunity to optimize long-term diabetes management, but clinical inertia is common. We previously reported the randomized study of a proactive inpatient diabetes service (RAPIDS), investigating an early intervention model of care and demonstrated improved in-hospital glycemia and clinical outcomes. This follow-up study assessed whether proactive care in hospital improved postdischarge HbA1c. In a subgroup of 298 RAPIDS trial participants with type 2 diabetes, age <80 years, and admission HbA1c ≥ 7.0%, diabetes treatment intensification occurred more often in early intervention versus usual care groups (37% vs. 19% [p = .001]), adjusted odds ratio 3.2 (95% confidence interval [CI]: 1.7-6.0). There was a greater change in HbA1c in the early intervention group (mean -0.9% [95% CI -1.3 to -0.4]) versus the usual care group (-0.3% [-0.6 to -0.1]), p = .029. The value of acute care by dedicated inpatient diabetes teams can extend beyond improving inpatient clinical outcomes and can lead to sustained improvement in glycemia.

USACE Coastal and Hydraulics Laboratory Quality Controlled, Consistent Measurement Archive.

The US Army Corps of Engineers (USACE) utilizes the National Oceanic and Atmospheric Administration (NOAA) National Data Buoy Center (NDBC) buoy measurements for validation of their wave models and within coastal applications. However, NDBC data are accessible via multiple archives; each with their own source-specific storage, metadata, and quality control protocols, which result in inconsistencies in the accessible data. Therefore, USACE has developed an independent, quality controlled, consistent (QCC) Measurement Archive that captures the best available NDBC observations with verified metadata. This work details the methodology behind this USACE QCC Measurement Archive; showcasing improvements in data quality via geographical location and wave parameter examples. Note that this methodology only removes known erroneous data, it does not verify data quality from an alternate source. This self-describing, USACE QCC Measurement Archive therefore provides a database of consistently stored, geographically QA/QC'd NDBC data and metadata.

Timing of heparin and perfusion temperature during procurement of organs with extracorporeal support in donors after circulatory determination of death.

Despite successful resuscitation of donors after circulatory determination of death (DCD) with extracorporeal support (ECS), the technique is limited by ethical concerns about donor management (heparinization) and the complexity to operate the ECS circuit. This work studies different timing of heparin administration and the effects of ECS-perfusion temperature. Cardiac arrest (CA) was induced in swine. Heparin studies, three groups: 1) PRE5, heparin 5 minutes before CA; 2) POST5, heparin 5 minutes after CA, plus 2 minutes external chest compressions; and 3) POST30, heparin with the initiation of ECS after 30 minutes CA. Perfusion temperature study, two groups: 1) normothermic, ECS-38.5°C after 30 minutes CA and 2) room temperature, ECS-25.5°C for the first 90 minutes, followed by ECS-38.5°C. Heparin studies: ECS target flows (>50 ml/kg/min) were not achieved in the POST30 group, affecting local organ perfusion as observed with poor bile (<4 ml/min) and urine output (<25 ml/min), when compared with the other groups (normal values). Temperature study: In both groups, ECS target flows were reached, and urine/bile output was restored. Heparinization 5 minutes after CA is equivalent to premortem heparinization in this ECS-DCD model. Heparinization after CA could reduce ethical concerns. Donors after circulatory determination of death were successfully resuscitated at both temperatures, suggesting that the heat exchanger/water heater can be removed to simplify the ECS circuit.

Quantification of thermal spread and burst pressure after endoscopic vessel harvesting: a comparison of 2 commercially available devices.

OBJECTIVE: Endoscopic vein harvesting systems have grown in popularity and are becoming the gold standard for coronary artery bypass grafting. Although a consensus is present that endoscopic vessel harvesting minimizes wound complications, long-term graft patency remains a concern. It has been proposed that endoscopic vessel harvesting affects graft patency because of irreversible trauma to the endothelium. This study was performed to examine the extent of thermal injury caused by 2 commercially available endoscopic vessel harvesting systems in a porcine model. METHODS: Superficial epigastric veins and saphenous arteries were exposed in 10 anesthetized swine. All vessel samples (conduits) were harvested randomly with either a VirtuoSaph (Terumo Cardiovascular, Ann Arbor, Mich) or VASOVIEW 6 (MAQUET, Inc, Wayne, NJ) endoscopic vessel harvesting system. Conduits were harvested and saved for either histologic analysis or burst-pressure test. Statistical differences were analyzed by using a Wilcoxon rank sum test in SAS 9.2 software (SAS Institute, Inc, Cary, NC) for thermal spread and a 2-tailed t test with equal variance for burst pressure. RESULTS: The average thermal spreads for saphenous artery and superficial epigastric vein conduits were significantly shorter in the VirtuoSaph group (0.42 ± 0.08 and 0.49 ± 0.05 mm, respectively) than in the VASOVIEW 6 group (1.05 ± .04 and 0.94 ± 0.19 mm, respectively). No significant differences were observed in burst pressure. CONCLUSIONS: The length of thermal spread is short in arterial and venous conduits (0.4-1.1 mm) and depends on the endoscopic vessel harvesting system. Clinical protocols should include a minimal length of the cauterized branch to ensure that thermal spread does not reach the main vessel. The results of this study suggest that at least 1 mm is sufficient.

Organ donation after cardiac determination of death (DCD): a swine model.

Donors after Cardiac Death (DCD) may reduce the organ scarcity; however, their use is limited because of warm ischemia time. Fortunately, this is less important in a subclass of DCD called expected (e-DCD), those with irreversible but incomplete brain injury. This study analyzed hemodynamic/pulmonary data to establish a clinically relevant model of cardiac death that would simulate an e-DCD setting. Hemodynamics, pulmonary artery flows, arterial blood gasses, and left atrial pressure were recorded q 5 minutes in anesthetized swine. After baseline data collection, the ventilator was discontinued and heparin was administered. Cardiac death was defined: as asystole, or mean arterial presusure < or = 25 mm Hg with a pulse pressure < or = 20 mm Hg. The time to death was approximately 14.8 minutes. Within 5 minutes of removal of the ventilator, there was a hyperdynamic period. Blood gases throughout the apneic time showed a rapid hypercapnia and acidosis. The hyperdynamic reflex response was followed by hypotension, bradycardia, and finally asystole or ventricular fibrillation. The protocol of withdrawal of ventilation, systemic anticoagulation, determination of death was developed to closely resemble the clinical e-DCD scenario. The physiologic changes that happen before death in DCD were described. An e-DCD model that can be used in studies related to organ transplantation was established.

Large animal model of chronic pulmonary hypertension.

A large animal model is needed to study artificial lung attachment in a setting simulating chronic lung disease with significant pulmonary hypertension (PH). This study sought to create a sheep model that develops significant PH within 60 days with a low rate of mortality. Sephadex beads were injected in the pulmonary circulation of sheep every other day for 60 days at doses of 0.5, 0.75, and 1 g (n = 10, 10, 7). Mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output were obtained every 2 weeks. In the 0.5, 0.75, and 1-g groups, 90, 70, and 14.3% of sheep completed the study, respectively, with the remainder experiencing heart failure. By the 60th day, pulmonary vascular resistance had increased (p < 0.01) from 0.89 +/- 0.3 to 3.2 +/- 0.9 mm Hg/(L/min) and from 0.9 +/- 0.3 to 4.3 +/- 3.2 mm Hg/(L/min) in the 0.5 and 0.75-g groups, respectively. Significant right ventricular hypertrophy was observed in the 0.75-g group but not in the 0.5-g group. Data from the 1-g group were insufficient for analysis due to high mortality. Thus, the 0.5 and 0.75-g groups generate significant PH, but the 0.75-g group is a better model of chronic PH in lung disease due to the development of right ventricular hypertrophy.

Thirty-day in-parallel artificial lung testing in sheep.

BACKGROUND: Thirty-day testing of the MC3 Biolung (MC3 Inc, Ann Arbor, MI) total artificial lung (TAL) was performed to prepare for future clinical testing. METHODS: TAL inlet and outlet grafts were sewn to the pulmonary artery and left atrium of 8 sheep (35.6 +/- 1.6 kg), and the TAL was attached the next day. Hemodynamic and sheep blood gas data were measured every 1 to 4 hours. TAL blood gases were measured twice daily, and organ function was assessed three times per week. The TAL was replaced if its resistance increased 300% or if the oxygen content difference across the TAL decreased 25% versus baseline. After 30 days, the sheep were euthanized and necropsied. RESULTS: Five sheep survived 30 days. Three sheep were euthanized before 30 days due to bleeding, mechanical graft failure, or gastric distress. Survivors had normal, stable hemodynamics and blood gases. Average device use was 9.5 +/- 2.1 days. TAL oxygen transfer was 108 +/- 9.2 mL/min with 51% +/- 6.3% of cardiac output flowing to the TAL. TAL resistance and flow were 1.3 +/- 0.3 mm Hg x min/L and 2.4 +/- 0.2 L/min at baseline versus 2.6 +/- 0.9 mm Hg x min/L and 2.0 +/- 0.2 L/min for the remaining 30 days. Platelet and white blood cell counts increased 88% and 84% from baseline, respectively, after 10 days and were stable thereafter. Ischemic lesions in the kidney were seen in most sheep at necropsy, but organ function was normal. CONCLUSIONS: Thirty-day respiratory support was feasible with the Biolung, but improvements in biocompatibility and anticoagulation regimen are warranted to reduce the thrombogenicity of the device.

Seven-day artificial lung testing in an in-parallel configuration.

BACKGROUND: A thoracic artificial lung, the MC3 Biolung, is being developed as a bridge to lung transplantation or as a treatment for acute respiratory insufficiency. METHODS: The thoracic artificial lung was tested in 10 sheep with the goal of 7 days of respiratory support. The sheep were recovered from surgery and monitored awake for 7 days. Hemodynamics, blood gases, blood cell counts, and organ function were recorded, and after 7 days, all sheep were euthanized and necropsied. RESULTS: Seven sheep survived the full duration. Cardiac output and mean arterial blood pressure were unchanged, averaging 4.7 +/- 0.8 L/min and 98 +/- 10 mm Hg, respectively. Arterial oxygen tension and device oxygen transfer rate were also unchanged, averaging 110 +/- 26 mm Hg and 97.7 +/- 35 mL/min, respectively. Arterial carbon dioxide tension was within normal ranges during the entire experiment, averaging 37.4 +/- 3.8 mm Hg. Artificial lung blood flow decreased from 51% +/- 14% of cardiac output on day 1 to 30% +/- 16% by day 7 because of changes in natural and artificial lung resistance. White blood cell counts were significantly elevated on days 5 and 7, and lastly, kidney and liver function remained normal, although signs of kidney infarction or hemorrhage were noted. CONCLUSIONS: The thoracic artificial lung is suitable for 7-day attachment, but improvements in blood biocompatibility are warranted.