Citations

Data from transgenic rodent models suggest that glucagon acts as an insulin secretagogue by signaling through the glucagon-like peptide 1 receptor (GLP-1R) present on β-cells. However, its net contribution to physiologic insulin secretion in humans is unknown. To address this question, we studied individuals without diabetes in two separate experiments. Each subject was studied on two occasions in random order. In the first experiment, during a hyperglycemic clamp, glucagon was infused at 0.4 ng/kg/min, increasing by 0.2 ng/kg/min every hour for 5 h. On one day, exendin-9,39 (300 pmol/kg/min) was infused to block GLP-1R, while on the other, saline was infused. The insulin secretion rate (ISR) was calculated by nonparametric deconvolution from plasma concentrations of C-peptide. Endogenous glucose production and glucose disappearance were measured using the tracer-dilution technique. Glucagon concentrations, by design, did not differ between study days. Integrated ISR was lower during exendin-9,39 infusion (213 ± 26 vs. 191 ± 22 nmol/5 h, saline vs. exendin-9,39, respectively; P = 0.02). In the separate experiment, exendin-9,39 infusion, compared with saline infusion, also decreased the β-cell secretory response to a 1-mg glucagon bolus. These data show that, in humans without diabetes, glucagon partially stimulates the β-cell through GLP-1R.

OBJECTIVES: To summarize the most impactful articles relevant to the pharmacotherapy of critically ill adult patients published in 2021. DATA SOURCE: PubMed/MEDLINE. STUDY SELECTION: Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critical care patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2021, and December 31, 2021. DATA EXTRACTION: Candidate articles were organized by clinical domain based on the emerging themes from all studies. A modified Delphi process was applied to obtain consensus on the most impactful publication within each clinical domain based on overall contribution to scientific knowledge and novelty to the literature. DATA SYNTHESIS: The search revealed 830 articles, of which 766 were excluded leaving 64 candidate articles for the Delphi process. These 64 articles were organized by clinical domain including: emergency/neurology, cardiopulmonary, nephrology/fluids, infectious diseases, metabolic, immunomodulation, and nutrition/gastroenterology. Each domain required the a priori defined three Delphi rounds. The resultant most impactful articles from each domain included five randomized controlled trials and two systematic review/meta-analyses. Topics studied included sedation during mechanical ventilation, anticoagulation in COVID-19, extended infusion beta-lactams, interleukin-6 antagonists in COVID-19, balanced crystalloid resuscitation, vitamin C/thiamine/hydrocortisone in sepsis, and promotility agents during enteral feeding. CONCLUSIONS: This synoptic review provides a summary and perspective of the most impactful articles relevant to the pharmacotherapy of critically ill adults published in 2021.

AbstractIntroductionType 1 diabetes mellitus occurs in one in every 275 pregnancies and can result in increased morbidity and mortality for both mother and baby. Several pregnancy complications can be reduced or prevented by attendance at pre‐pregnancy care (PPC). Despite this, less than 40% of pregnant women with pre‐gestational diabetes receive formal PPC. The aim of this scoping review is to identify the barriers to PPC attendance among women with type 1 diabetes.MethodsWe conducted a scoping review by searching five databases (Ebsco, Embase, Ovid and PubMed for literature and the ProQuest for any grey/unpublished literature) for studies in English between 2000 and 2022. Studies that evaluated attendance at PPC for women with type 1 diabetes were included.ResultsThere are multiple barriers to PPC attendance, and many of these barriers have been unchanged since the 1990s. Identified barriers can be grouped under patient‐centered and clinician‐centered headings. Patient factors include knowledge and awareness, unplanned pregnancies, negative perceptions of healthcare and communication issues, unclear attendance pathways and logistical issues including time off work and childcare. Clinician factors include physician knowledge, time constraints and lack of comfort discussing pregnancy/contraception.ConclusionThis review highlights the ongoing problem of poor attendance at PPC and identifies key barriers to be addressed when developing and implementing PPC programs for women with type 1 diabetes.

Introduction: Cryoablation of intercostal nerves is performed for pain control after minimally invasive repair of pectus excavatum (MIRPE). Cryoablation affects both sensory and motor neurons, resulting in temporary anesthesia to the chest wall and loss of intercostal motor function. The study objective is to determine the effect of cryoablation on incentive spirometry (IS) volumes, as a measure of pulmonary function, after MIRPE. Materials and Methods: A single-institution retrospective review of pediatric patients undergoing MIRPE was performed. All patients received a multimodal regimen (MMR) of analgesics postoperatively. Three groups were compared—cryoablation (CRYO), elastomeric pain pump (EPP), and MMR alone. The primary outcomes were postoperative IS volumes and IS volumes as a ratio of preoperative forced vital capacity (FVC). Secondary outcomes included pain scores, opioid use, length of stay (LOS), and infectious complications. Results: MIRPE was performed in 115 patients: 50 CRYO, 50 EPP, and 15 MMR alone. Groups were similar for demographics and pectus excavatum severity. Postoperative spirometry measurements were similar across groups: IS (CRYO 750 mL [500,961] versus EPP 750 mL [590,1019] versus MMR 696 mL [500,1037], P = .77); IS/FVC (CRYO 0.19 [0.14,0.26] versus EPP 0.20 [0.16,0.26] versus MMR 0.16 [0.15,0.24], P = .69). Although pain scores were also similar across groups, CRYO patients used less opioid ( P < .05) and had shorter LOS ( P < .05). Postoperative pneumonia was rare and similar across groups ( P = 1.00). Conclusion: Intercostal nerve cryoablation during MIRPE does not adversely affect postoperative IS volumes or increase pneumonia rate, despite the temporary loss of motor innervation to intercostal muscles. Cryoablation provides effective pain control with less opioid use.

ImportanceCytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.ObjectiveTo determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.ExposuresImmunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).Main Outcomes and MeasuresThe primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.ResultsThe median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).Conclusions and RelevanceThis cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.Trial RegistrationClinicalTrials.gov Identifier: NCT04354701

Diabetic ketoacidosis (DKA) is an obstetrical emergency that is associated with an elevated risk of adverse pregnancy outcomes. This includes pregnancy loss in up to 1 in 3 cases. Due to the normal metabolic changes that occur during pregnancy, females who are pregnant are more vulnerable to DKA, and it can occur at lesser than expected degrees of hyperglycaemia. Presenting symptoms can be non-specific and include nausea and vomiting, fatigue, polydipsia, and polyuria. DKA may be the first presentation of previously undiagnosed diabetes. Therefore, high index of suspicion, along with prompt diagnosis and management, is essential. The cornerstones of management include intravenous insulin, intravenous fluids, and electrolyte replacement. Treatment generally follows the principles for DKA management outside of pregnancy, with some additional considerations. Close maternal and fetal monitoring is essential, and intensive care unit admission is typically required to adequately achieve this goal. In all situations, a thorough investigation should occur to address the underlying cause of the DKA and prevent further episodes. This review article outlines the potential etiopathogenesis, clinical presentation, and management of DKA in pregnancy.

Abstract Context Diabetic ketoacidosis (DKA) in pregnancy is an obstetric emergency with risk of maternofetal death. Objective This work aimed to evaluate DKA events in pregnant women admitted to our inpatient obstetric service, and to examine associated clinical risk factors, presentation, and pregnancy outcomes. Methods A retrospective cohort study was conducted at the Mayo Clinic, Rochester, Minnesota, USA, and included women aged 17 to 45 years who were treated for DKA during pregnancy between January 1, 2004 and December 31, 2021. Main outcome measures included maternal and fetal death along with a broad spectrum of maternal and fetal pregnancy outcomes. Results A total of 71 DKA events were identified in 58 pregnancies among 51 women, 48 (82.8%) of whom had type 1 diabetes. There were no maternal deaths, but fetal demise occurred in 10 (17.2%) pregnancies (6 miscarriages and 4 stillbirths). Maternal social stressors were frequently present (n = 30, 51.0%), and glycemic control was suboptimal (median first trimester glycated hemoglobin A1c = 9.0%). Preeclampsia was diagnosed in 17 (29.3%) pregnancies. Infants born to women with DKA were large for gestational age (n = 16, 33.3%), suffered from neonatal hypoglycemia (n = 29, 60.4%) and required intensive care unit admission (n = 25, 52.1%). Conclusion DKA is associated with a high rate of maternofetal morbidity and fetal loss. Prenatal education strategies for women with diabetes mellitus should include a strong focus on DKA prevention, and clinicians and patients should have a high index of suspicion for DKA in all pregnant women who present with symptoms that could be attributed to this condition.