Continuous Glucose Monitoring Reveals Perioperative Hypoglycemia in Most Patients With Diabetes Undergoing Major Surgery: A Prospective Cohort Study.

OBJECTIVE: To investigate the frequency and duration of hypo- and hyperglycemia, assessed by continuous glucose monitoring (CGM) during and after major surgery, in departments with implemented diabetes care protocols. SUMMARY BACKGROUND DATA: Inadequate glycemic control in the perioperative period is associated with serious adverse events, but monitoring currently relies on point blood glucose measurements, which may underreport glucose excursions. METHODS: Adult patients without (A) or with diabetes [non-insulin-treated type 2 (B), insulin-treated type 2 (C) or type 1 (D)] undergoing major surgery were monitored using CGM (Dexcom G6), with an electrochemical sensor in the interstitial fluid, during surgery and for up to 10 days postoperatively. Patients and health care staff were blinded to CGM values, and glucose management adhered to the standard diabetes care protocol. Thirty-day postoperative serious adverse events were recorded. The primary outcome was duration of hypoglycemia (glucose <70 mg/dL). Clinicaltrials.gov: NCT04473001. RESULTS: Seventy patients were included, with a median observation time of 4.0 days. CGM was recorded in median 96% of the observation time. The median daily duration of hypoglycemia was 2.5 minutes without significant difference between the 4 groups (A-D). Hypoglycemic events lasting ≥15 minutes occurred in 43% of all patients and 70% of patients with type 1 diabetes. Patients with type 1 diabetes spent a median of 40% of the monitoring time in the normoglycemic range 70 to 180 mg/dL and 27% in the hyperglycemic range >250 mg/dL. Duration of preceding hypo- and hyperglycemia tended to be longer in patients with serious adverse events, compared with patients without events, but these were exploratory analyses. CONCLUSIONS: Significant duration of both hypo- and hyperglycemia was detected in high proportions of patients, particularly in patients with diabetes, despite protocolized perioperative diabetes management.

Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children.

BACKGROUND: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. METHODS: We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. RESULTS: Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. CONCLUSIONS: Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections.

Wireless Single-Lead ECG Monitoring to Detect New-Onset Postoperative Atrial Fibrillation in Patients After Major Noncardiac Surgery: A Prospective Observational Study.

BACKGROUND: New-onset postoperative atrial fibrillation (POAF) is associated with several cardiovascular complications and higher mortality. Several pathophysiological processes such as hypoxia can trigger POAF, but these are sparsely elucidated, and POAF is often asymptomatic. In patients undergoing major gastrointestinal cancer surgery, we aimed to describe the frequency of POAF as automatically estimated and detected via wireless repeated sampling monitoring and secondarily to describe the association between preceding vital sign deviations and POAF. METHOD: Patients ≥60 years of age undergoing major gastrointestinal cancer surgery were continuously monitored for up to 4 days postoperatively. Electrocardiograms were obtained every minute throughout the monitoring period. Clinical staff were blinded to all measurements. As for the primary outcome, POAF was defined as 30 consecutive minutes or more detected by a purpose-built computerized algorithm and validated by cardiologists. The primary exposure variable was any episode of peripheral oxygen saturation (Spo2) <85% for >5 consecutive minutes before POAF. RESULTS: A total of 30,145 hours of monitoring was performed in 398 patients, with a median of 92 hours per patient (interquartile range [IQR], 54-96). POAF was detected in 26 patients (6.5%; 95% confidence interval [CI], 4.5-9.4) compared with 14 (3.5%; 95% CI, 1.94-5.83) discovered by clinical staff in the monitoring period. POAF was followed by 9.4 days hospitalization (IQR, 6.5-16) versus 6.5 days (IQR, 2.5-11) in patients without POAF. Preceding episodes of Spo2 <85% for >5 minutes (OR, 1.02; 95% CI, 0.24-4.00; P = .98) or other vital sign deviations were not significantly associated with POAF. CONCLUSIONS: New-onset POAF occurred in 6.5% (95% CI, 4.5-9.4) of patients after major gastrointestinal cancer surgery, and 1 in 3 cases was not detected by the clinical staff (35%; 95% CI, 17-56). POAF was not preceded by vital sign deviations.

Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects.

Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.

Airway immune mediator levels during asthma-like symptoms in young children and their possible role in response to azithromycin.

BACKGROUND: Asthma-like symptoms in young children are orchestrated by the local airway immune response, but current knowledge largely relies on in vitro airway models. Azithromycin has been shown to reduce the duration of episodes with asthma-like symptoms, but efficacy may depend on the individual child's immune response. OBJECTIVES: To investigate in vivo upper airway immune mediator levels during episodes with asthma-like symptoms in young children and their ability to predict the clinical response to azithromycin treatment. METHODS: A total of 535 children aged 0-3 years from the Copenhagen Prospective Studies of Asthma in Childhood-2010 mother-child cohort were examined for immune mediator levels in samples of nasal epithelial lining fluid during episodes with asthma-like symptoms as well as in the asymptomatic state. In a sub-study, children with recurrent asthma-like symptoms were randomized to either a 3-day course of oral azithromycin (10 mg/kg; n = 32) or placebo (n = 38). In the current study, we compared the pretreatment immune mediator levels with the clinical response to treatment with azithromycin in an exploratory post hoc analysis. RESULTS: The immune mediator concentrations during vs outside episodes were significantly upregulated for IFN-É£ (ratio 1.73), TNF-α (ratio 2.05), IL-1ß (ratio 1.45), IL-10 (ratio 1.97), while CCL22 (ratio 0.65) was downregulated. Low levels of TNF-α and IL-10 and high levels of CCL22 predicted better treatment response to azithromycin (P-values < .05). CONCLUSION: Upper airway immune mediator levels were altered during episodes of asthma-like symptoms, and levels of TNF-α, CCL22, and IL-10 may predict the response to azithromycin treatment.

Neonatal airway immune profiles and asthma and allergy endpoints in childhood.

BACKGROUND: The immune system plays a key role in the pathogenesis of asthma and allergy, but the role of the airway cytokine and chemokine composition in vivo in early life prior to symptom development has not been described previously. Here, we aimed to examine whether the neonatal airway immune composition associates with development of allergy and asthma in childhood. METHODS: We measured unstimulated levels of 20 immune mediators related to the Type 1, Type 2, Type 17, or regulatory immune pathways in the airway mucosal lining fluid of 620 one-month-old healthy neonates from the COPSAC2010 birth cohort. Allergy and asthma were diagnosed at our research clinic by predefined algorithms and objective assessments at age 6 years. Principal component analyses were used to describe the airway cytokine and chemokine composition. RESULTS: A neonatal airway immune profile particularly characterized by enhanced IL-1ß and reduced CCL26 was significantly associated with later development of elevated specific IgE to inhaled allergens, a positive skin prick test, and allergic rhinitis, but not with food sensitization. Conversely, reduced Type 17 immune-associated markers, including IL-1ß and CXCL8, showed trend of association with development of early asthma endpoints. CONCLUSIONS: Development of early asthma endpoints and inhalant allergy during the first 6 years of life seems associated with distinctly perturbed airway immune profiles in neonatal life, which is suggestive of an early origin and different pathogenesis of childhood asthma and allergy. These exploratory findings suggest pre- and perinatal life as an important window of opportunity for prevention of asthma and inhalant allergy.

Cadherin-related Family Member 3 Genetics and Rhinovirus C Respiratory Illnesses.

RATIONALE: Experimental evidence suggests that CDHR3 (cadherin-related family member 3) is a receptor for rhinovirus (RV)-C, and a missense variant in this gene (rs6967330) is associated with childhood asthma with severe exacerbations. OBJECTIVES: To determine whether rs6967330 influences RV-C infections and illnesses in early childhood. METHODS: We studied associations between rs6967330 and respiratory infections and illnesses in the COPSAC2010 (Copenhagen Prospective Studies on Asthma in Childhood 2010) and COAST (Childhood Origins of Asthma Birth Cohort Study) birth cohorts, where respiratory infections were monitored prospectively for the first 3 years of life. Nasal samples were collected during acute infections in both cohorts and during asymptomatic periods in COAST and analyzed for RV-A, RV-B, and RV-C, and other common respiratory viruses. MEASUREMENTS AND MAIN RESULTS: The CDHR3 asthma risk allele (rs6967330-A) was associated with increased risk of respiratory tract illnesses (incidence risk ratio [IRR] = 1.14 [95% confidence interval, 1.05-1.23]; P = 0.003). In particular, this variant was associated with risk of respiratory episodes with detection of RV-C in COPSAC2010 (IRR = 1.89 [1.14-3.05]; P = 0.01) and in COAST (IRR = 1.37 [1.02-1.82]; P = 0.03) children, and in a combined meta-analysis (IRR = 1.51 [1.13-2.02]; P = 0.006). In contrast, the variant was not associated with illnesses related to other viruses (IRR = 1.07 [0.92-1.25]; P = 0.37). Consistent with these observations, the CDHR3 variant was associated with increased detection of RV-C, but not of other viruses during scheduled visits at specific ages. CONCLUSIONS: The CDHR3 asthma risk allele is associated specifically with RV-C illnesses in two birth cohorts. This clinical evidence supports earlier molecular evidence indicating that CDHR3 functions as an RV-C receptor, and raises the possibility of preventing RV-C infections by targeting CDHR3.

Duration of wheezy episodes in early childhood is independent of the microbial trigger.

BACKGROUND: Wheezy episodes in young children are often triggered by viral and bacterial respiratory tract infections, but there is little evidence supporting the hypothesis that symptom duration depends on the specific microbial trigger. OBJECTIVE: We sought to investigate whether the duration of wheezy episodes in young children depends on the microbial trigger. METHODS: Two hundred eighty-three children from the Copenhagen Prospective Study on Asthma in Childhood2000 at-risk birth cohort were prospectively examined for common airway pathogenic bacteria and viruses during acute wheezy episodes in the first 3 years of life. Findings were related to symptomatic duration of episodes, as monitored in daily diary cards from birth. RESULTS: Eight hundred thirty-seven samples were investigated for viruses, bacteria, or both. Both viruses and bacteria were identified in 55% of episodes, bacteria were identified exclusively in 31% of episodes, and viruses were identified exclusively in 10% of episodes. The median duration of acute symptoms was 9 days (interquartile range, 5-16 days), and duration was independent of bacterial or viral species. CONCLUSIONS: The duration of wheezy episodes was independent of pathogenic airway bacterial or viral species. This suggests that symptom burden from infections is dependent on other factors, such as environmental exposures or host factors. The common term viral wheeze seems inappropriate in view of the finding of pathogenic bacteria in 86% of wheezy episodes.

An evaluation of the interference of hydroxycobalamin with chemistry and co-oximetry tests on nine commonly used instruments.

The administration of hydroxocobalamin (OHCob), alone or with sodium thiosulfate, is a standard therapy for cyanide poisoning. OHCob is a red chromophore, and its interference with co-oximetric and colorimetric laboratory measurements has been evaluated in a few conflicting reports. The interference of OHCob was investigated in samples spiked with 10 different concentrations of OHCob (0-1500 mg/L). The concentration of 73 different analytes was measured using nine different analysers (ABL 800 Flex, Advia 1800, Advia Centaur Xp, Architect ci8200, Immulite 2500, Konelab 30i, Modular Analytics SWA, Synchron LX 20 and Vitros 5.1). All instruments yielded some results that were affected by OHCob at concentrations equivalent to a single therapeutic dose. Of the 73 different analytes, 64% showed interference on at least one instrument. Of all 187 tests performed, 47% were biased with more than 10%. Interference was generally limited to photometric assays, whereas immunological and ion-selective electrode measurements were unaffected. OHCob present in the blood after treatment for cyanide poisoning interfered with many laboratory assays in an unpredictable way, making some results invalid. Some affected tests are important in the treatment of cyanide poisoning. The interference is not solely due to wavelength, but also to chemical interaction. Without delaying the administration of OHCob, blood should, preferably, be drawn in advance, or, at least, the laboratory should be informed about the OHCob treatment. If the laboratory receives OHCob-containing samples, methods and instruments should be selected to minimize bias, and the manufacturer of the OHCob should recommend relevant precautions to customers in the package insert.

Agreement Between Transcutaneous Monitoring and Arterial Blood Gases During COPD Exacerbation.

BACKGROUND: Transcutaneous measurements of CO2 and O2 ([Formula: see text], [Formula: see text]) are noninvasive and allow for continuous monitoring in adults with exacerbation of COPD, but substantial accuracy issues may exist. We investigated agreement between results of arterial blood gas analysis and transcutaneous measurements of CO2 and O2 in patients with COPD. METHODS: Adult subjects were monitored after acute admission to a respiratory intermediate care unit or ICU due to exacerbation of COPD and with ongoing noninvasive ventilation or immediately following extubation. Monitored variables were continuous transcutaneous measurement and simultaneous routine arterial blood gas analysis. Agreement between measurements was assessed by calculating bias with 95% limits of agreement for single-point estimates of [Formula: see text] versus [Formula: see text] and versus [Formula: see text], and for changes in transcutaneous measurements between 2 time points ([Formula: see text] and [Formula: see text]). We considered limits of agreement within ± 7.5 mm Hg to be acceptable. RESULTS: A total of 57 transcutaneous measurements were made in 20 subjects for comparison with concurrent arterial blood gas analysis at 36 time points. The bias (limits of agreement) for [Formula: see text] and [Formula: see text] was 2.5 mm Hg (-10.6 to 15.6 mm Hg) and 11.2 mm Hg (-28.2 to 50.6 mm Hg), respectively. The bias for [Formula: see text] and [Formula: see text] was 2.3 mm Hg (-3.8 to 8.3 mm Hg) and -5.3 mm Hg (-37.5 to 27 mm Hg), respectively. CONCLUSIONS: [Formula: see text] and [Formula: see text] did not accurately reflect results from arterial blood gas analyses in this study of mostly hypercapnic subjects. Agreement between changes in CO2 during the monitoring period was acceptable, however, and transcutaneous monitoring may be used for continuous monitoring of [Formula: see text] in conjunction with arterial blood gas analysis for reference.