ObjectivesPrevious fMRI studies have demonstrated that glucose decreases the hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS response to glucose have not been defined. We recently demonstrated that the slowing of gastric emptying by glucose is dependent on activation of the gut peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic resonance imaging this study aimed to determine the whole brain response to glucose, and whether CCK plays a central role.Experimental designChanges in blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12 healthy subjects following intragastric infusion (250 ml) of: 1 M glucose + predosing with dexloxiglumide (CCK1 receptor antagonist), 1 M glucose + placebo, or 0.9% saline (control) + placebo, in a single-blind, randomised fashion. Gallbladder volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined. Hunger, fullness and nausea scores were also recorded.Principal observationsIntragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD signal, relative to saline, in the brainstem and hypothalamus as well as the cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD signal decrease was negatively correlated with the rise in blood glucose and insulin levels. The glucose + dex arm highlighted a CCK1-receptor dependent increase in BOLD signal only in the motor cortex.ConclusionsGlucose induces site-specific differences in BOLD response in the human brain; the brainstem and hypothalamus show a CCK1 receptor-independent reduction which is likely to be mediated by a circulatory effect of glucose and insulin, whereas the motor cortex shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1 receptor-dependent neural pathway.

Pregnancy Associated Breast Cancer (PABC) manifests during pregnancy or within a year following delivery. We sought to investigate differences in management, outcome, clinical, histopathology and immunohistochemistry (IHC) characteristics of PABC and matched controls in a retrospective case control study. PABC and control patients were selected from breast cancer cases of women ≤45 years, diagnosed in the

BackgroundBased on its mechanism of action, PARP inhibitor therapy is expected to benefit mainly tumor cases with homologous recombination deficiency (HRD). Therefore, identification of tumor types with increased HRD is important for the optimal use of this class of therapeutic agents. HRD levels can be estimated using various mutational signatures from next generation sequencing data and we used this approach to determine whether breast cancer brain metastases show altered levels of HRD scores relative to their corresponding primary tumor.Patients and methodsWe used a previously published next generation sequencing dataset of 21 matched primary breast cancer/brain metastasis pairs to derive the various mutational signatures/HRD scores strongly associated with HRD. We also carried out the myChoice HRD analysis on an independent cohort of 17 breast cancer patients with matched primary/brain metastasis pairs.ResultsAll of the mutational signatures indicative of HRD showed a significant increase in the brain metastases relative to their matched primary tumor in the previously published whole exome sequencing dataset. In the independent validation cohort, the myChoice HRD assay showed an increased level in 87.5% of the brain metastases relative to the primary tumor, with 56% of brain metastases being HRD positive according to the myChoice criteria.ConclusionsThe consistent observation that brain metastases of breast cancer tend to have higher HRD measures may raise the possibility that brain metastases may be more sensitive to PARP inhibitor treatment. This observation warrants further investigation to assess whether this increase is common to other metastatic sites as well, and whether clinical trials should adjust their strategy in the application of HRD measures for the prioritization of patients for PARP inhibitor therapy.

ObjectivesTo investigate the cardiovascular consequences of SARS-CoV-2 infection in highly trained, otherwise healthy athletes using cardiac magnetic resonance (CMR) imaging and to compare our results with sex-matched and age-matched athletes and less active controls.MethodsSARS-CoV-2 infection was diagnosed by PCR on swab tests or serum immunoglobulin G antibody tests prior to a comprehensive CMR examination. The CMR protocol contained sequences to assess structural, functional and tissue-specific data.ResultsOne hundred forty-seven athletes (94 male, median 23, IQR 20–28 years) after SARS-CoV-2 infection were included. Overall, 4.7% (n=7) of the athletes had alterations in their CMR as follows: late gadolinium enhancement (LGE) showing a non-ischaemic pattern with or without T2 elevation (n=3), slightly elevated native T1 values with or without elevated T2 values without pathological LGE (n=3) and pericardial involvement (n=1). Only two (1.4%) athletes presented with definite signs of myocarditis. We found pronounced sport adaptation in both athletes after SARS-CoV-2 infection and athlete controls. There was no difference between CMR parameters, including native T1 and T2 mapping, between athletes after SARS-CoV-2 infection and the matched athletic groups. Comparing athletes with different symptom severities showed that athletes with moderate symptoms had slightly greater T1 values than athletes with asymptomatic and mildly symptomatic infections (p<0.05). However, T1 mapping values remained below the cut-off point for most patients.ConclusionAmong 147 highly trained athletes after SARS-CoV-2 infection, cardiac involvement on CMR showed a modest frequency (4.7%), with definite signs of myocarditis present in only 1.4%. Comparing athletes after SARS-CoV-2 infection and healthy sex-matched and age-matched athletes showed no difference between CMR parameters, including native T1 and T2 values.

Aims Physiological cardiac adaptation in athletes is influenced by multiple factors. This study aimed to investigate the impact of sex, age, body size, sports type and training volume on cardiac adaptation in healthy athletes with cardiac magnetic resonance imaging. Methods A total of 327 athletes (242 male) were studied (adults ≥18 years old; adolescents 14–18 years old). Left and right ventricular ejection fractions, end-diastolic volume, end-systolic volume, stroke volumes and masses were measured. Left ventricular end-diastolic volume/left ventricular mass, right ventricular end-diastolic volume/right ventricular mass and derived right/left ventricular ratios were determined to study balanced ventricular adaptation. Athletes were categorised as skill, power, mixed and endurance athletes. Results Male athletes had higher left and right ventricular volumes and masses in both adult ( n = 215 (145 male); 24 ± 5 years old) and adolescent ( n = 112 (97 male); 16 ± 1 years old) groups compared with women (all P < 0.05). In adults, male sex, age, body surface area, weekly training hours, mixed and endurance sports correlated with higher ventricular volumes and masses (all P < 0.05); and a combination of age, sex, training hours, endurance and mixed sports explained 30% of the variance of the left ventricular end-diastolic volume index ( r = 0.30), right ventricular end-diastolic volume index ( r = 0.34), right ventricular mass index ( r = 0.30); and as much as 53% of the left ventricular mass index ( r = 0.53) (all P < 0.0001). In adolescents, positive correlations were found between training hours and left ventricular hypertrophy ( r = 0.39, P < 0.0001), and biventricular dilation (left ventricular end-diastolic volume r = 0.34, P = 0.0008; right ventricular end-diastolic volume r = 0.36, P = 0.0004). In adolescents, age and body surface area did not correlate with cardiac magnetic resonance parameters. Conclusion There are significant sex differences in the physiological adaptation of adult and adolescent athlete’s heart; and male sex, higher training volume and endurance sports are major determinants of sports adaptation in adults.