Reduced pulmonary diffusing capacity for carbon monoxide (DLCO) can be observed in pulmonary arterial hypertension (PAH) and associates with increased mortality. However, the prognostic value of DLCO ...when corrected for haemoglobin (DLCOc), an independent modifier of DLCO, remains understudied. Additionally, the prognostic role of ventilation (V)–perfusion (Q) emission computed tomography (V/Q SPECT) findings in patients with PAH, which may concurrently be performed to rule out chronic thromboembolic pulmonary hypertension, is uncertain. A retrospective cohort study was conducted on 152 patients with PAH referred to a tertiary hospital for evaluation from January 2011 to January 2020. Lung function tests, clinical data and V/Q SPECT were ascertained. Cox regression analysis was performed to evaluate the association between DLCOc, DLCO and V/Q SPECT defects at referral with all‐cause mortality. In equally adjusted Cox regression analysis, each percentage increase in DLCOc % predicted (%pred) (hazard ratio (HR) 0.97; 95% CI: 0.94–0.99) and DLCO%pred (HR 0.97; 95% CI: 0.94–0.99) was similarly associated with all‐cause mortality. There was no detectable difference in area under the curve for prediction of all‐cause mortality by DLCOc%pred and DLCO%pred (C‐index 0.71 and 0.72, respectively, P = 0.85 for difference). None of the defects noted on V/Q SPECT were significantly associated with mortality, but mismatched defects were associated with lower values of DLCOc%pred and DLCO%pred. DLCOc%pred and DLCO%pred perform equally as prognostic markers in PAH, supporting the use of either metric when available for prognostic stratification.
What is the central question of this study?
Does haemoglobin correction of the pulmonary diffusing capacity for carbon monoxide improve prognostic stratification in patients with pulmonary arterial hypertension (PAH)?
What is the main finding and its importance?
In PAH, the pulmonary diffusing capacity for carbon monoxide predicts all‐cause mortality equally well regardless of whether it is haemoglobin‐corrected or not. Either metric can therefore be used for the diagnostic workup of these patients. Ancillary findings on ventilation–perfusion emission computed tomography concurrently performed to rule out chronic thromboembolic pulmonary hypertension did not inform prognosis further.
Aim
To examine whether adults with mild to moderate atopic dermatitis (AD) had reduced insulin sensitivity and/or exhibited other gluco‐metabolic disturbances compared with carefully matched healthy ...controls.
Materials and methods
Sixteen adult, non‐obese, non‐diabetic patients with mild to moderate AD and 16 gender‐, age‐ and body mass index (BMI)‐matched healthy controls underwent a hyperinsulinaemic euglycaemic clamp (insulin infusion rate: 40 mU/m2/minute) and an oral glucose tolerance test (OGTT) with frequent blood sampling for gut and pancreatic hormones.
Results
The two groups were similar in age (33 ± 3 vs. 33 ± 3 years, mean ± standard error of the mean SEM), gender (56% women), BMI (24.5 ± 0.7 vs. 24.4 ± 0.7 kg/m2), physical activity level, fasting plasma glucose and HbA1c. Patients with AD had a mean Eczema Area and Severity Index score of 8.5 ± 1.0 (moderate disease) and a mean AD duration of 28 ± 3 years. During the OGTT, circulating glucose, insulin, C‐peptide, glucagon and glucose‐dependent insulinotropic polypeptide, respectively, were similar in the two groups, except glucagon‐like peptide‐1, which was higher in patients with AD. The clamp showed no differences in insulin sensitivity between groups (M‐value 9.2 ± 0.6 vs. 9.8 ± 0.8, P = .541, 95% CI −1.51; 2.60), or circulating insulin, C‐peptide and glucagon levels.
Conclusions
Using OGTT and the hyperinsulinaemic euglycaemic clamp technique, we found no difference in insulin sensitivity or other gluco‐metabolic characteristics between patients with mild to moderate AD and matched healthy controls, suggesting that the inflammatory skin disease AD has little or no influence on glucose metabolism.
Atrioventricular nodal reentry tachycardia (AVNRT) is the most common form of regular paroxysmal supraventricular tachycardia. This arrhythmia affects women twice as frequently as men, and is often ...diagnosed in patients <40 years of age. Familial clustering, early onset of symptoms and lack of structural anomaly indicate involvement of genetic factors in AVNRT pathophysiology. We hypothesized that AVNRT patients have a high prevalence of variants in genes that are highly expressed in the atrioventricular conduction axis of the heart and potentially involved in arrhythmic diseases. Next-generation sequencing of 67 genes was applied to the DNA profile of 298 AVNRT patients and 10 AVNRT family members using HaloPlex Target Enrichment System. In total, we identified 229 variants in 60 genes; 215 missenses, four frame shifts, four codon deletions, three missense and splice sites, two stop-gain variants, and one start-lost variant. Sixty-five of these were not present in the Exome Aggregation Consortium (ExAC) database. Furthermore, we report two AVNRT families with co-segregating variants. Seventy-five of 284 AVNRT patients (26.4%) and three family members to different AVNRT probands had one or more variants in genes affecting the sodium handling. Fifty-four out of 284 AVNRT patients (19.0%) had variants in genes affecting the calcium handling of the heart. We furthermore find a large proportion of variants in the HCN1-4 genes. We did not detect a significant enrichment of rare variants in the tested genes. This could be an indication that AVNRT might be an electrical arrhythmic disease with abnormal sodium and calcium handling.
The exact mechanism linking the systemic inflammatory response associated with sepsis to changes in lung function remains to be determined. In a human experimental model of inflammation, we ...investigated how acute systemic and local pulmonary inflammation affects ventilatory capacity and pulmonary gas exchange. Fifteen volunteers received Escherichia coli lipopolysaccharide (LPS) intravenously or endobronchially on two different study days. Blood samples were obtained hourly (t = 0–8 h) and spirometry was performed at baseline and after 8 h. Both interventions decreased ventilatory capacity compared to baseline (p < 0.01), and this was more pronounced after intravenous (forced expiratory volume in 1‐s, FEV1; 0.6 L/12% reduction) compared to endobronchial (FEV1; 0.32 L/7% reduction) administration (p < 0.05). Furthermore, the alveolar‐arterial oxygen difference increased after intravenous but not after endobronchial endotoxin. These findings indicate that pulmonary gas exchange is impaired to a greater extent during endotoxin‐induced systemic inflammation than during endotoxin‐induced local pulmonary inflammation.
A basic understanding of acid-base physiology is critical for the correct assessment of arterial blood gases in the clinical setting. In this context, collaborative teaching strategies in the ...undergraduate classroom setting may be useful, since it has been reported to enhance both transfer and retention of learned material in a time-efficient fashion. In a previous study, the authors found that conventional group work and peer instruction equally enabled second-year medical students to diagnose common acid-base disorders immediately after class, indicating successful transfer of the learned material. This article describes a 2-yr followup study in which they investigated whether these collaborative strategies also lead to long-term retention of the learned skills.
We conducted a randomized, single-blinded study of the effect of alcohol intake during a hangover. We measured cardiovascular parameters, and the participants filled out a series of questionnaires ...regarding their well-being. We found, that an intake of five beers led to a significant decrease in systolic blood pressure, heart rate and self-reported feeling of palpitations. However, the self-reported sense of well-being did not improve. In addition, we found that the risk of brain freeze increased, as the beer's temperature fell.
Human personality is characterized by substantial heritability but few functional gene variants have been identified. Although rodent data suggest that the neuronal isoform of nitric oxide synthase ...(NOS-I) modifies diverse behaviors including aggression, this has not been translated to human studies.
To investigate the functionality of an NOS1 promoter repeat length variation (NOS1 Ex1f variable number tandem repeat VNTR) and to test whether it is associated with phenotypes relevant to impulsivity.
Molecular biological studies assessed the cellular consequences of NOS1 Ex1f VNTR; association studies were conducted to investigate the impact of this genetic variant on impulsivity; imaging genetics was applied to determine whether the polymorphism is functional on a neurobiological level.
Three psychiatric university clinics in Germany.
More than 3200 subjects were included in the association study: 1954 controls, 403 patients with personality disorder, 383 patients with adult attention-deficit/hyperactivity disorder (ADHD), 151 with familial ADHD, 189 suicide attempters, and 182 criminal offenders.
For the association studies, the major outcome criteria were phenotypes relevant to impulsivity, namely, the dimensional phenotype conscientiousness and the categorical phenotypes adult ADHD, aggression, and cluster B personality disorder.
A novel functional promoter polymorphism in NOS1 was associated with traits related to impulsivity, including hyperactive and aggressive behaviors. Specifically, the short repeat variant was more frequent in adult ADHD, cluster B personality disorder, and autoaggressive and heteroaggressive behavior. This short variant came along with decreased transcriptional activity of the NOS1 exon 1f promoter and alterations in the neuronal transcriptome including RGS4 and GRIN1. On a systems level, it was associated with hypoactivation of the anterior cingulate cortex, which is involved in the processing of emotion and reward in behavioral control.
These findings implicate deficits in neuronal signaling via nitric oxide in moderation of prefrontal circuits underlying impulsivity-related behavior in humans.
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