Characteristics and prognosis of isolated aortic valve infective endocarditis in patients with bicuspid aortic valves: a propensity matched study.

Introduction: Bicuspid aortic valve (BAV) is the most common congenital heart disease with an increased risk of infective endocarditis (IE). Few data are available on isolated native BAV-IE. The aim of this study was to compare patients with tricuspid aortic valve (TAV) IE and BAV-IE in terms of characteristics, management and prognosis. Material and methods: We included 728 consecutive patients with IE on isolated native aortic valve in 3 centres: Amiens and Marseille Hospitals in France and Salerno Hospital in Italy. We studied in hospital and long-term mortality before and after matching for age, sex and comorbidity index. Median follow-up was 67.2 [IQR: 19-120] months. Results: Of the 728 patients, 123 (16.9%) had BAV. Compared with patients with TAV-IE, patients with BAV-IE were younger, had fewer co-morbidities and were more likely to be male. They presented more major neurological events and perivalvular complications (both p < 0.05). Early surgery (<30 days) was performed in 52% of BAV-IE cases vs. 42.8% for TAV-IE (p = 0.061). The 10-year survival rate was 74 ± 5% in BAV-IE patients compared with 66 ± 2% in TAV-IE patients (p = 0.047). After propensity score matching (for age, gender and comorbidities), there was no difference in mortality between the two groups, with an estimated 10-year survival of 73 ± 5% vs. 76 ± 4% respectively (p = 0.91). Conclusion: BAV is a frequent finding in patients with isolated aortic valve IE and is associated with more perivalvular complications and neurological events. The differences in survival with TAV-IE are probably related to the age and comorbidity differences between these two populations.

Neurodevelopmental Outcomes of Extremely Low Birth Weight Survivors in Johannesburg, South Africa.

Background: Improved survival in extremely low birth weight infants (ELBWI) in Sub-Saharan Africa has raised the question whether these survivors have an increased chance of adverse neurodevelopmental outcomes. Objectives: To describe neurodevelopmental outcomes of ELBWI in a neonatal unit in South Africa. Methods: This was a prospective follow-up study. All ELBWI who survived to discharge between 1 July 2013 and 31 December 2017 were invited to attend the clinic. Bayley Scales of Infant and Toddler Development (version III) were conducted at 9 to 12 months and 18 to 24 months. Results: There were 723 ELBWI admissions during the study period, 292 (40.4%) survived to hospital discharge and 85/292 (29.1%) attended the neonatal follow up clinic. The mean birth weight was 857.7 g (95% CI: 838.2-877.2) and the mean gestational age was 27.5 weeks (95% CI 27.1-27.9). None of the infants had any major complication of prematurity. A total of 76/85 (89.4%) of the infants had a Bayley-III assessment at a mean corrected age of 17.21 months (95% CI: 16.2-18.3). The mean composite scores for cognition were 98.4 (95% CI 95.1-101.7), language 89.9 (95% CI 87.3-92.5) and motor 97.6 (95% CI 94.5-100.6). All mean scores fell within the normal range, The study found 28 (36.8%) infants to be "at risk" for neurodevelopmental delay. Conclusion: Our study demonstrates good neurodevelopmental outcome in a small group of surviving ELBWI, but these results must be interpreted in the context of the high mortality in this group of infants.

Dilated cardiomyopathy: the role of genetics, highlighted in a family with Filamin C (FLNC) variant.

Dilated cardiomyopathy (DCM) is a heterogenous group of disorders characterised by left ventricular dilatation and dysfunction, in the absence of factors affecting loading conditions such as hypertension or valvular disease, or significant coronary artery disease. The prevalence of idiopathic DCM is estimated between 1:250 and 1:500 individuals. Determining the aetiology of DCM can be challenging, particularly when evaluating an individual and index case with no classical history or investigations pointing towards an obvious acquired cause, or no clinical clues in the family history to suggest a genetic cause. We present a family affected by DCM associated with Filamin C variant, causing sudden cardiac death at a young age and heart failure due to severe left ventricular impairment and myocardial scarring. We review the diagnosis and treatment of DCM, its genetic associations and potential acquired causes. Thorough assessment is mandatory to risk stratify and identify patients who may benefit from primary prevention implantable cardioverter defibrillator therapy according to international guidelines. Genetic testing has some limitations, and is positive in only 20%-35% of DCM, but should be considered in specific cases to identify families who may benefit from cascade screening after appropriate counselling. The management of often complex familial cardiomyopathy requires specialist input for every case, and the appropriate infrastructure to coordinate investigations.

Unusual, Radical Treatment of Type A Aortic Dissection: A Case Report.

Type A aortic dissection, according to Stanford classification, is a surgical emergency with high morbidity and carries 56% of in-hospital mortality when surgical intervention is not performed. The surgical mortality at 30 days is 10 to 20%. The therapeutic goals are to replace the diseased ascending aorta and to treat or to monitor the distal aortic patent false lumen. When the dissection involves the aortic root and the architecture of aortic valve is normal, the surgical techniques used could be multiple: reinforce the aortic root and spare the native aortic valve or replace the aortic valve and the aortic root. The Florida sleeve technique has been developed to treat the aortic aneurysm, sparing the aortic valve in patients with connective tissue disease. Some case reports have described the use of this technique to treat an acute aortic dissection. In the following case, we present a single stage repair of the ascending aorta, aortic arch, and proximal intrathoracic aorta in a patient with Type A aortic dissection through the contemporaneous use of two techniques: Florida sleeve and Vascutek "Thoraflex" hybrid prosthesis. The use of these two techniques allows the repair/replacement of the proximal intrathoracic aorta, the sparing of the native aortic valve, the employment of a hybrid prosthesis to replace the supraortic vessels, and the creation of a descending aortic landing zone for later, distal intervention.

Infective endocarditis and diabetes mellitus: Results from a single-center study from 1994 to 2017.

BACKGROUND: To evaluate the prognostic impact of diabetes mellitus (DM) in patients with Infective Endocarditis (IE). METHODS AND RESULTS: 375 patients with diagnosis of IE referred to our Hospital between 1994-2017 were retrospectively included; diabetes was reported in 129 (34.4%). Diabetic patients were older than non-diabetic (66±1 vs. 57±2 years, p<0.001) and showed a higher prevalence of comorbidities such as hypertension (75 vs. 54%, p<0.001), coronary artery disease (30 vs. 12%, p<0.001) and history of heart failure (HF; 24 vs. 13%, p = 0.021). Echocardiography showed a higher incidence of paravalvular complications (82 vs. 64%, p<0.001) and a lower left ventricular ejection fraction (LVEF; 52±11 vs. 55±10%, p = 0.001) in diabetic than in non-diabetic patients. In-hospital mortality was higher in diabetic patients (83 vs. 74%; p = 0.030). At logistic regression, history of HF (OR = 3.1, 95%CI: 1.87-5.29, p<0.001) resulted an independent predictor of in-hospital death. At long-term follow-up [median 24(7-84) months], the Kaplan-Meier analysis showed a significantly lower survival free from all-cause death in the group with diabetes (Log-rank<0.001). At the propensity score adjusted Cox multivariable analysis, DM (HR = 1.76, 95%CI: 1.18-2.6, p = 0.005), age (HR = 1.03, 95%CI: 1.02-1.05, p<0.001), intravenous drug users (HR = 5.42, 95%CI: 2.55-11.51, p<0.001) and low LVEF (HR = 0.98, 95%CI: 0.96-0.99, p = 0.013) were independently associated to a higher mortality. CONCLUSION: In patients with IE, DM is associated to a higher prevalence of anatomic complications and a more impaired LVEF. Diabetic patients show a significantly lower survival both in hospital and during follow-up compared to the non-diabetic ones.

Cognitive impairment in patients with psoriasis: A matched case-control study.

BACKGROUND: In the past decade, a few studies have suggested that psoriasis could be associated with the presence of mild cognitive deficits. OBJECTIVES: The aim of the present matched case-control study was to investigate several cognitive domains (executive functions, verbal memory, attention, and language) in a sample of outpatients with psoriasis. We also investigated whether cognitive impairment was associated with poor health-related quality of life (HRQoL) in patients with psoriasis. METHODS: Fifty adult outpatients and 50 age- and sex-matched healthy controls were administered a battery of neuropsychological tests investigating major cognitive domains, psychopathology (anxiety and depression), alexithymia, and HRQoL. RESULTS: At the bivariate level, psoriasis patients (compared to healthy controls) performed worse on most of the neuropsychological tests, and they also reported more anxiety and depressive symptoms, higher scores for alexithymia, and worse physical and mental health. At the multivariate level, cognitive performance was independently associated with psoriasis even when controlling for psychopathology and alexithymia. CONCLUSIONS: Patients with psoriasis show impaired cognitive performance, high levels of anxiety and depression, and impaired quality of life. Based on the current results, clinicians should assess the presence of psychological symptoms in their patients and evaluate whether the presence of cognitive deficits is limiting the patients' ability to cope with the disease.

Response to isolated limb perfusion and chemotherapy with epirubicin plus ifosfamide in a metastatic malignant ossifying fibromyxoid tumor.

BACKGROUND: Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain lineage and intermediate biological potential. It is more common in middle-aged men, usually arising from the deep tissues of the extremities. It is now established that it is a translocation related tumor, most often marked by translocation of PHF1 gene. Surgery is the mainstay of treatment and proves usually curative, although, in rarer cases the disease shows malignant features and tendency to recur both locally and at distant sites. In such cases, no standard treatment exists. CASE PRESENTATION: We report on a case of malignant advanced OFMT of the hand with lung metastases responding to isolated limb perfusion with human recombinant tumor necrosis factor and melphalan and chemotherapy with epirubicin and ifosfamide. CONCLUSIONS: To our knowledge, this is the first report of activity of soft tissue sarcoma-oriented chemotherapy in advanced OFMT.

Uncertainty in Antibiotic Dosing in Critically Ill Neonate and Pediatric Patients: Can Microsampling Provide the Answers?

PURPOSE: With a decreasing supply of antibiotics that are effective against the pathogens that cause sepsis, it is critical that we learn to use currently available antibiotics optimally. Pharmacokinetic studies provide an evidence base from which we can optimize antibiotic dosing. However, these studies are challenging in critically ill neonate and pediatric patients due to the small blood volumes and associated risks and burden to the patient from taking blood. We investigate whether microsampling, that is, obtaining a biologic sample of low volume (<50 µL), can improve opportunities to conduct pharmacokinetic studies. METHODS: We performed a literature search to find relevant articles using the following search terms: sepsis, critically ill, severe infection, intensive care AND antibiotic, pharmacokinetic, p(a)ediatric, neonate. For microsampling, we performed a search using antibiotics AND dried blood spots OR dried plasma spots OR volumetric absorptive microsampling OR solid-phase microextraction OR capillary microsampling OR microsampling. Databases searched include Web of Knowledge, PubMed, and EMbase. FINDINGS: Of the 32 antibiotic pharmacokinetic studies performed on critically ill neonate or pediatric patients in this review, most of the authors identified changes to the pharmacokinetic properties in their patient group and recommended either further investigations into this patient population or therapeutic drug monitoring to ensure antibiotic doses are suitable. There remain considerable gaps in knowledge regarding the pharmacokinetic properties of antibiotics in critically ill pediatric patients. Implementing microsampling in an antibiotic pharmacokinetic study is contingent on the properties of the antibiotic, the pathophysiology of the patient (and how this can affect the microsample), and the location of the patient. A validation of the sampling technique is required before implementation. IMPLICATIONS: Current antibiotic regimens for critically ill neonate and pediatric patients are frequently suboptimal due to a poor understanding of altered pharmacokinetic properties. An assessment of the suitability of microsampling for pharmacokinetic studies in neonate and pediatric patients is recommended before wider use. The method of sampling, as well as the method of bioanalysis, also requires validation to ensure the data obtained reflect the true result.

Health-related quality of life and its association with alexithymia and difficulties in emotion regulation in patients with psoriasis.

BACKGROUND: Health-related quality of life (HRQoL) in psoriasis patients could be negatively affected by medical (e.g., obesity) and psychological (e.g., depression, anxiety, and alexithymia) conditions the presence of which suggests difficulties in understanding and regulating inner states and emotions. Thus, the aim of this study was to investigate HRQoL and its association with obesity and difficulties in understanding and regulating inner states and emotions in patients with psoriasis. A second objective was to examine whether the presence of difficulties in understanding and regulating inner states and emotions may mediate the association between psoriasis and poor HRQoL. METHOD: One hundred adult outpatients and 97 healthy controls were administered a checklist assessing major socio-demographic variables, and measures of HRQoL, difficulties in emotion regulation, alexithymia, anxiety, depression, and food craving. RESULTS: Psoriasis patients (compared to controls) reported more frequently obesity, alexithymia, anxiety, depression and food craving, and reported lower scores on the mental and physical components of HRQoL. A mediation model, with mental health as the dependent variable, indicated significant direct and indirect (through BMI, difficulties in emotion regulation, anxiety, depression, and food craving) effects of psoriasis on the quality of life, so that psoriasis was associated with worse mental health. A second mediation model with physical health as dependent variable indicated only a significant indirect effect (through BMI and depression) of psoriasis on the quality of life. CONCLUSIONS: Psoriasis is characterized by poor HRQoL and the presence of difficulties in understanding and regulating inner states and emotions. In patients with psoriasis the possible influence of food craving on abnormal eating habits should be carefully assessed.

Is there a role for microsampling in antibiotic pharmacokinetic studies?

INTRODUCTION: Clinical pharmacokinetic studies of antibiotics can establish evidence-based dosing regimens that improve the likelihood of eradicating the pathogen at the site of infection, reduce the potential for selection of resistant pathogens, and minimize harm to the patient. Innovations in small volume sampling (< 50 µL) or 'microsampling' may result in less-invasive sample collection, self-sampling and dried storage. Microsampling may open up opportunities in patient groups where sampling is challenging. AREAS COVERED: The challenges for implementation of microsampling to assure suitability of the results, include: acceptable study design, regulatory agency acceptance, and meeting bioanalytical validation requirements. This manuscript covers various microsampling methods, including dried blood/plasma spots, volumetric absorptive microsampling, capillary microsampling, plasma preparation technologies and solid-phase microextraction. EXPERT OPINION: The available analytical technology is being underutilized due to a lack of bridging studies and validated bioanalytical methods. These deficiencies represent major impediments to the application of microsampling to antibiotic pharmacokinetic studies. A conceptual framework for the assessment of the suitability of microsampling in clinical pharmacokinetic studies of antibiotics is provided. This model establishes a 'contingency approach' with consideration of the antibiotic and the type and location of the patient, as well as the more prescriptive bioanalytical validation protocols.

Contribution of IBD5 locus to clinical features of IBD patients.

AIM: The aim of this study was to investigate the influence of the IBD5 locus on clinical features of inflammatory bowel disease (IBD) patients, and its possible interaction with the CARD15 gene. PATIENTS AND METHODS: A cohort of 1,199 IBD patients (570 with CD and 629 with ulcerative colitis [UC]), and 357 healthy subjects were investigated. Information on clinical features was fully available for 855 IBD patients. Two SNPs in the IBD5 locus (IGR2198a_1 and IGR2096a_1) and the three major variants of CARD15 gene were genotyped in patients and controls. RESULTS: Homozygous carriers of risk alleles were significantly more frequent in CD (22.6% for IGR2198a_1, OR = 1.6, p = 0.015; 21.9% for IGR2096a_1, OR = 1.6, p = 0.012) compared to controls (16.8% and 15.7%, respectively). The homozygote frequency was also increased in UC patients, but not significantly. No significant gene-gene interaction was detected between IBD5 and CARD15. A univariate analysis detected association between IBD5 and steno/fistulizing behavior in CD patients (OR = 1.9; p = 0.004), and presence of more extensive colitis in UC patients (OR = 1.7; p = 0.01). Results from multiple logistic regression, after correction for covariates, showed that the influence of IBD5 on clinical outcome of CD was completely masked by that of CARD15, while the influence on more extensive colitis in UC patients was confirmed. CONCLUSIONS: Our study shows that presence of the IBD5 risk alleles, particularly in the homozygous state, is associated with IBD and especially with CD, without a significant epistasis with CARD15. The contribution of CARD15 risk alleles to CD clinical features is prominent on that of IBD5.

[Epidemiological stratification of malaria in Madagascar]. / Stratification épidémiologique du paludisme à Madagascar.

Madagascar is considered as a sub-region of the Afrotropical geographical Region in spite of the high endemicity of 95% of the invertebrates. Nevertheless the three malaria vectors An. gambiae s.s., An. arabiensis and An. funestus are quite similar to those of the continental Africa. This support the hypothesis of their recent introduction. Plasmodium falciparum is the dominant parasite but the prevalence of P. vivax is not negligible. It is linked to the Asian component of the human population. P. malariae and P. ovale are of minor importance. The main epidemiological "facies" of Africa are found in Madagascar. The equatorial facies on the East Coast is characterized by a high transmission all year long. In the tropical facies on the West Coast transmission is seasonal (7 months at least). In both areas, malaria is stable and the inhabitants acquire a high immunity before the age of ten; most of the severe cases touch children below 10. The three vectors can be found but An. gambiae s.s. is dominant. In the exophilic southern facies the transmission is seasonal (two to four months). The only vector is An. arabiensis. Malaria is unstable and severe epidemics occur during the years of high rainfall. All age groups are vulnerable because the population is not immune in the Plateaux facies above 1,000 m., malaria is unstable. Severe epidemics occurred in 1987-1988. The vectors are An. Arabiensis and An. funestus. The occurrence of P. falciparum on the Plateaux seems linked to the development of irrigation of rice farming in the XIXth century. Most of the anopheles breeding places on the Plateaux are dependent on rice cultivation. Urban development has brought the inhabitants of the suburbs in close contact with rice fields. Despite the high number of anopheline bites the number of malaria cases remains by far lower than in the neighbouring rural areas. Regional migrations inside the island bring non-immune populations, from the south and the plateaux, in highly malarious areas of the coast, where the migrants are exposed to high risk. In spite of 40 years of uncontrolled use, chloroquine can still cure most, if not all, of malaria cases. Control measures appropriated to the different areas of Madagascar are discussed.