Identification and management of invasive mycoses in internal medicine: a road-map for physicians

Invasive mycoses are a rising problem, not only in traditional categories of patients like hematologic or neutropenic ones, but also in elderly non-neutropenic patients admitted to internal medicine wards. Patients being admitted to medical wards are usually older, have multiple comorbidities, e.g., liver cirrhosis or chronic obstructive respiratory disease, may be malnourished or receive peripheral or total parenteral nutrition, and frequently are undergoing chronic corticosteroid therapy, chemotherapy for cancer or monoclonal antibodies for autoimmune diseases. Such risk factors may be contemporarily present in a single patient increasing the risk for the development of invasive mycoses. Diagnosis of candidemia and invasive aspergillosis is particularly difficult in patients hospitalized on medical wards, since symptoms and signs have low specificity, and most diagnostic tests have been only validated in neutropenic hematologic patients, but not in those without neutropenia. Both candidemia and invasive aspergillosis carry significant morbidity and mortality. The aim of this paper is to provide a simple guide to physicians for a prompt identification and treatment of patients with possible or suspected invasive mycoses.     

The association among food addiction,binge eating severity and psychopathology in obese and overweight patients attending low-energy-diet therapy

Several studies have shown that food addiction (FA) is strongly related with psychopathology. However, this relationship may be partly mediated by the presence and severity of binge eating. The aim of the current study was to assess the strength of the association between FA and psychopathology, and whether this relationship was mediated by the presence and severity of binge eating. Participants were 112 patients seeking weight loss interventions. All the participants were administered the Yale Food Addiction Scale (YFAS), The Symptom Check list-90-R (SCL-90), and the Binge Eating Scale (BES). Thirty-eight (33.9%) individuals were diagnosed as having FA. FA severity was strongly associated with binge eating, whereas both FA and binge eating were positively and moderately associated with psychopathology. A mediational model analyzing direct and indirect (through the mediating role of binge eating) effects of FA on psychopathology indicated that the relation between FA and psychopathology was fully mediated by the severity of binge eating. This finding suggests that FA may contribute to the development of psychopathology through its effect on binge eating.     

Proteome-Scale Antibody Responses and Outcome of Mycobacterium tuberculosis Infection in Nonhuman Primates and in Tuberculosis Patients

Background.Biomarkers of progression from latent Mycobacterium tuberculosis infection to active tuberculosis are needed. We assessed correlations between infection outcome and antibody responses in macaques and humans by high-throughput, proteome-scale serological studies. Methods.Mycobacterium tuberculosis proteome microarrays were probed with serial sera from macaques representing various infection outcomes and with single-point human sera from tuberculosis suspects. Fluorescence intensity data were analyzed by calculating Z scores and associated P values. Temporal changes in macaque antibody responses were analyzed by polynomial regression. Correlations between human responses and sputum bacillary burden were assessed by quantile and hurdle regression. Results.Macaque outcome groups exhibited distinct antibody profiles: early, transient responses in latent infection and stable antibody increase in active and reactivation disease. In humans, antibody levels and reactive protein numbers increased with bacillary burden. Responses to a subset of 10 proteins were more tightly associated with disease state than reactivity to the broader reactive proteome. Conclusions.Integration of macaque and human data reveals dynamic properties of antibody responses in relation to outcome and leads to actionable findings for translational research. These include the potential of antibody responses to detect acute infection and preclinical tuberculosis and to identify serodiagnostic proteins for the spectrum of bacillary burden in tuberculosis.     

Intra-aortic balloon pumping recruits graft flow reserve by lowering coronary resistances

Background

The intra-aortic balloon pump (IABP) is used worldwide as an anti-ischemic strategy and to reduce myocardial workload. However, whether IABP augments coronary flow after coronary bypass via a passive increase in diastolic pressure or an active response of the coronary bed remains uncertain.

Methods

We analyzed transit-time flow measurements and the contemporary changes in coronary resistances obtained during 1:1 IABP and during its cessation in 144 consecutive patients receiving prophylactic IABP before isolated coronary artery bypass grafting (n = 340 graft segments).

Results

Normally functioning grafts showed lower coronary resistances, greater percentage decrease in resistance, and greater increases in average maximum diastolic and mean flow during 1:1 IABP compared with IABP cessation (P < .001). Arterial and sequential saphenous vein grafts showed better flowmetry and greater reductions in coronary resistances compared with single venous grafts. Accordingly, graft flow reserve (defined as mean flow during 1:1 IABP/mean flow with IABP off) was recruited (graft flow reserve > 1) during 1:1 IABP in all normally functioning grafts, with higher values in single arterial or sequential saphenous vein grafts than in single venous grafts (both P < .001). Coronary resistances were higher in 7 failed grafts versus normal-functioning grafts at baseline; these did not decrease during 1:1 IABP and showed worse transit-time flow results.

Conclusions

IABP recruits graft flow reserve by lowering coronary resistance in functioning grafts. Arterial and sequential venous grafts showed greater reduction in coronary resistance compared with single saphenous grafts.     

Assessment of central adrenal insufficiency in children and adolescents with Prader-Willi syndrome

Objective A recent study evidenced by metyrapone test a central adrenal insufficiency (CAI) in 60% of Prader–Willi syndrome (PWS) children. These results were not confirmed in investigations with low [Low‐Dose Tetracosactrin Stimulation Test (LDTST), 1 μg] or standard‐dose tetracosactrin stimulation tests. We extended the research by LDTST in paediatric patients with PWS. Design Cross‐sectional evaluation of adrenal stress response to LDTST in a PWS cohort of a tertiary care referral centre. Patients Eighty‐four children with PWS. Measurements Assessment of adrenal response by morning cortisol and ACTH dosage, and 1‐μg tetracosactrin test. Response was considered appropriate when cortisol reached 500 nm ; below this threshold, patients were submitted to a second test. Responses were correlated with the patients’ clinical and molecular characteristics to assess genotype–phenotype correlation. Results Pathological cortisol peak responses to the LDTST were registered in 12 patients (14·3%) who had reduced basal (169·4 ± 83·3 nm ) and stimulated (428·1 ± 69·6 nm ) cortisol levels compared to patients with normal responses (367·1 ± 170·6 and 775·9 ± 191·3 nm , P < 0·001). Body mass index standard deviation score was negatively correlated with basal and peak cortisol levels (both P < 0·001), and the patients’ ages (P < 0·001). In patients with deletion on chromosome 15, the cortisol peak was significantly lower than that in uniparental disomy (UPD) cases (P = 0·030). At multiple regression analysis, the predictors of peak response were basal cortisol, age, and UPD subclass (r² = 0·353, P < 0·001). Standard‐dose (250 μg) tetracosactrin test confirmed CAI in 4/12 patients (4·8% of the cohort). Conclusions Our results support the hypothesis that, albeit rare, CAI may be part of the PWS in childhood.     

The p.A382T TARDBP gene mutation in Sardinian patients affected by Parkinson's disease and other degenerative parkinsonisms

Based on our previous finding of the p.A382T founder mutation in ALS patients with concomitant parkinsonism in the Sardinian population, we hypothesized that the same variant may underlie Parkinson's disease (PD) and/or other forms of degenerative parkinsonism on this Mediterranean island. We screened a cohort of 611 patients with PD (544 cases) and other forms of degenerative parkinsonism (67 cases) and 604 unrelated controls for the c.1144G > A (p.A382T) missense mutation of the TARDBP gene. The p.A382T mutation was identified in nine patients with parkinsonism. Of these, five (0.9 % of PD patients) presented a typical PD (two with familiar forms), while four patients (6.0 % of all other forms of parkinsonism) presented a peculiar clinical presentation quite different from classical atypical parkinsonism with an overlap of extrapyramidal–pyramidal–cognitive clinical signs. The mutation was found in eight Sardinian controls (1.3 %) consistent with a founder mutation in the island population. Our findings suggest that the clinical presentation of the p.A382T TARDBP gene mutation may include forms of parkinsonism in which the extrapyramidal signs are the crucial core of the disease at onset. These forms can present PSP or CBD-like clinical signs, with bulbar and/or extrabulbar pyramidal signs and cognitive impairment. No evidence of association has been found between TARDBP gene mutation and typical PD.     

Nodo-paranodopathy: Beyond the demyelinating and axonal classification in anti-ganglioside antibody-mediated neuropathies

In some anti-ganglioside antibody-mediated neuropathies, human and experimental data suggest a common pathogenic mechanism of dysfunction/disruption at the node of Ranvier resulting in a pathophysiologic continuum from transitory nerve conduction failure to axonal degeneration. The traditional classification of polyneuropathies into demyelinating or axonal may generate some confusion in the electrophysiological diagnosis of Guillain–Barré syndrome subtypes associated with anti-ganglioside antibodies. The axonal forms show, besides axonal degeneration, promptly reversible nerve conduction failure. This may be interpreted, by a single electrophysiological study, as demyelinating conduction block or distal axonal degeneration leading to errors in classification and in establishing prognosis. Moreover the term axonal may be misleading as it is commonly associated to axonal degeneration and not to a transitory, promptly reversible, dysfunction of the excitable axolemma. To focus on the site of nerve injury and overcome the classification difficulties, we propose the new category of nodo-paranodopathy which seems appropriate to various acute and chronic neuropathies associated with anti-ganglioside antibodies and we think better systematizes the neuropathies characterized by an autoimmune attack targeting the nodal region.