Rationale and study design of the RESERVOIR trial: a randomized trial comparing reservoir-based polymer-free amphilimus-eluting stents versus everolimus-eluting stents with durable polymer in patients with diabetes mellitus.

BACKGROUND: Patients with diabetes mellitus (DM) remain at high risk for stent restenosis and adverse cardiovascular events in the drug-eluting stent era. The amphilimus-eluting stent (AES) is a third generation reservoir-based polymer-free drug-eluting stent that has shown promising preliminary results in patients with DM. It has been suggested that the formulation of the drug with fatty acids could not only modulate the drug release in a timely manner but also achieve convenient levels of drug concentration in diabetic cardiac cells. The aim of this trial is to assess the efficacy of the AES in patients with DM compared with the cobalt chromium everolimus-eluting stent with non-erodible polymer (EES). STUDY DESIGN: This is an investigator-initiated, multicenter, randomized clinical trial, performed in patients with DM. A total of 112 diabetic patients receiving glucose-lowering agents and requiring percutaneous revascularization of a de novo lesion will be randomized in a 1:1 fashion to receive AES or EES. The primary endpoint is the neointimal volume obstruction at 9 months, evaluated by optical coherence tomography. Secondary endpoints will include strut coverage, angiographic in-stent late loss and clinical endpoints such as target vessel revascularization or probable/definite stent thrombosis. This study completed the inclusion in October 2013. CONCLUSIONS: The RESERVOIR trial is an investigator-initiated trial that will evaluate whether the polymer-free AES is not inferior to the EES inhibiting the neointimal hyperplasia in patients with DM. These results are also expected to improve our knowledge of the neointimal healing process in this population (Clinicaltrials.gov number NCT01710748).

Neurohormonal activation induces intracellular iron deficiency and mitochondrial dysfunction in cardiac cells.

BACKGROUND: Iron deficiency (ID) is common in patients with heart failure (HF) and is associated with poor outcomes, yet its role in the pathophysiology of HF is not well-defined. We sought to determine the consequences of HF neurohormonal activation in iron homeostasis and mitochondrial function in cardiac cells. METHODS: HF was induced in C57BL/6 mice by using isoproterenol osmotic pumps and embryonic rat heart-derived H9c2 cells were subsequently challenged with Angiotensin II and/or Norepinephrine. The expression of several genes and proteins related to intracellular iron metabolism were assessed by Real time-PCR and immunoblotting, respectively. The intracellular iron levels were also determined. Mitochondrial function was analyzed by studying the mitochondrial membrane potential, the accumulation of radical oxygen species (ROS) and the adenosine triphosphate (ATP) production. RESULTS: Hearts from isoproterenol-stimulated mice showed a decreased in both mRNA and protein levels of iron regulatory proteins, transferrin receptor 1, ferroportin 1 and hepcidin compared to control mice. Furthermore, mitoferrin 2 and mitochondrial ferritin were also downregulated in the hearts from HF mice. Similar data regarding these key iron regulatory molecules were found in the H9c2 cells challenged with neurohormonal stimuli. Accordingly, a depletion of intracellular iron levels was found in the stimulated cells compared to non-stimulated cells, as well as in the hearts from the isoproterenol-induced HF mice. Finally, neurohormonal activation impaired mitochondrial function as indicated by the accumulation of ROS, the impaired mitochondrial membrane potential and the decrease in the ATP levels in the cardiac cells. CONCLUSIONS: HF characteristic neurohormonal activation induced changes in the regulation of key molecules involved in iron homeostasis, reduced intracellular iron levels and impaired mitochondrial function. The current results suggest that iron could be involved in the pathophysiology of HF.

Study of factors that influence the outcome of 131I treatment in hyperthyroidism secondary to nodular goitre. / Estudio de los factores que influyen en el resultado del tratamiento con 131I en el hipertiroidismo por bocio nodular.

OBJECTIVE: To assess the outcome after 131I treatment in patients with multinodular (MNG) and nodular toxic goitre (NTG) according to the administered dose and other factors related to the patient, pathology, or previous treatments. MATERIAL AND METHODS: A retrospective study was conducted on 108 patients (67 MNG and 41 NTG) treated in our department, with a follow-up period of at least 2 years. Development of hypothyroidism and treatment failure were evaluated along with their relationship with the administered dose and other factors such as age, sex, grade of hyperthyroidism, type of goitre, presence of autoimmunity, or previous antithyroid medication. RESULTS: More than one-third (36.9%) of MNG patients, and even higher proportion of NTG patients (51.2%) developed non-transient hypothyroidism, particularly in those receiving 740MBq (66.7%). No relationship was found with any other variable. The development of early hypothyroidism (before one year) was also not related to any variable. Treatment failure was not related to the dose, but in MNG there was a relationship with male gender, presence of autoimmunity, or previous antithyroid drugs use. CONCLUSIONS: The high rate of hypothyroidism obtained with high doses of 131I in hyperthyroidism secondary to nodular goitre treatment suggests that lower doses might be sufficient to control the disease without an increase in treatment failures. Only patients with positive autoimmunity, in previous anti-thyroid medication, and perhaps male gender in MNG might be given higher doses, as the failure rate increases, but further studies are required.

[Carbapenem resistance in Pseudomonas aeruginosa isolated from urine cultures: prevalence and risk factors]. / Resistencia a carbapenemas en Pseudomonas aeruginosa aisladas en urocultivos: prevalencia y factores de riesgo.

OBJECTIVE: Pseudomonas aeruginosa is a non-fermentative gram-negative bacillus with a great ability to develop resistance to multiple antibiotics, including carbapenems, which is a growing problem worldwide. The aim of this study was to analyse the prevalence of carbapenem-resistant P. aeruginosa (CRPA) in urine cultures and to determine the risk factors associated with the development of carbapanem resistance. METHODS: Positive urine cultures to P. aeruginosa between September 2012 and September 2014 were identified. We excluded repetitive cultures from the same patient. We created a database with different variables, including antimicrobial resistance. The prevalence of carbapenem resistance and the risk factors for growth of CRPA were analysed. RESULTS: Ninety-one patients with positive urine cultures to P. aeruginosa were included. The prevalence of CRPA was 22%. The risk factors to CRPA infection in the univariate analysis were: congestive heart failure (p=0.02), previous treatment with ampicillin (p=0.04), meropenem (p=0.04), piperacillin-tazobactam (p=0.01), trimethoprim-sulfamethoxazole (p= 0.01) and previous treatment with more than one antibiotic (p<0.01). Only congestive heart failure (p<0.01) and previous treatment with more than one antibiotic (p<0.01) showed statistically significant differences in the multivariate analysis. CONCLUSIONS: The prevalence of CRPA in urine cultures is high in our population. We should assess the presence of risk factors as previous treatment with more than one antibiotic or comorbidities such as heart failure, in order to select an appropriate empirical treatment in patients with severe urinary tract infections.

[Juvenile parkinsonism. 18 cases]. / Parkinsonismo juvenil. A propósito de 18 casos.

The accepted Juvenile Parkinson denomination includes patients who present the characteristic symptoms before 40 years old. We are reporting 18 such patients, between 15 and 34 years old, who had a follow-up between 9 to 17 years. Based on our observations and a revision of the literature, and after considering inheritance, clinical, evolutive and therapeutic outlook we were able to reach a conclusion as to the essential features of this particular form of parkinsonism. Apparently the impairment to L-Dopa therapy developed more slowly in these patients than in presenile forms and it would be related more with the duration of the illness than with that of L-Dopa therapy.

Antiplatelet therapy: new pharmacological agents and changing paradigms.

Recurrent atherothrombotic events in patients with acute coronary syndromes (ACS) and/or those undergoing percutaneous coronary intervention (PCI) are essentially platelet-driven processes, underscoring the need for effective pharmacological platelet inhibition. Dual antiplatelet therapy with aspirin and clopidogrel has been, for over a decade, the mainstay of antiplatelet management in ACS/PCI. However, atherothrombotic events continue to occur in a relevant proportion of subjects despite the benefit of this combination, which has led to the clinical development of newer and more potent antiplatelet drugs. Two of these, prasugrel and ticagrelor, have been recently approved for clinical use. The scope of this manuscript is to provide an up-to-date overview on new antiplatelet drugs in the setting of ACS and PCI, including the most recent advances on newly approved agents as well as on emerging compounds in clinical development.

[Chronic toluene poisoning]. / Intoxicación crónica por tolueno.

The long-term inhalation of compounds in which toluene is the main ingredient leads to the damage of both central and peripheral nervous system. We present the case of a 24 year-old man who, sniffing these compounds since he was 17, slowly develops a variegated syndrome including psychiatric impairment, signs of bilateral pyramidalism, cerebellar and sensitive alterations, and peripheral neuropathy. CT scan, electrophysiological and laboratory modifications are reported. A comparative study with other reports is made, reviewing the associated pathology to this form of chronic intoxication, caused by the noxious action of each one of these substances or by their interaction. Liposolubility is established as the main pathogenic factor of this intoxication.

[Optic neuropathy caused by amiodarone]. / Neuropatía óptica por amiodarona.

Amiodarone has been used for the last 20 years, initially as antianginal and then as antiarrhythmic agent. To the collateral effects described, the optic neuropathy must be added as a complication, not so frequent, caused apparently by the prolonged ingestion of it. Two patients treated with MDD of 250 mg of amiodarone, for a mean of 17 months, are reported. They presented a decrease of the visual acuity. After proposing the possible differential diagnosis, the relation between the use of amiodarone and the optic alteration observed is briefly exposed, relating it with the demyelination neuropathy induced by this drug. This presumption is corroborated by the ultrastructural alterations registered in the optic nerve of animals in which amiodarone was used, similar to those of the peripheral nerves, as an expression of a disorder of the lipidic metabolism, which allow it to be integrated to the so called iatrogenic lipidoses.

[Osteoarticular infections caused by Streptococcus agalactiae. Report of 4 cases]. / Infecciones osteoarticulares por Streptococcus agalactiae. Aportación de 4 casos.

BACKGROUND: Streptococcus agalactiae (group B streptococcus) is a rare etiology of osteoarticular infection in adults. In a literature review (Medline-Embase plus) up until may 1994, we have found only 51 cases. In most patients, diabetes mellitus, liver disease or long-term steroid therapy were documented. METHODS: Four adult patients with osteoarticular infection due to S. agalactiae from two Galician hospitals were studied from January 1988 to October 1994: prepatellar bursitis (one case), septic monoarthritis (2 cases) and psoas abscess associated to cervical spondylodiscitis and oligoarthritis (left sternoclavicular and left hip joints). RESULTS: In the first patient, a young woman with prepatellar bursitis, a previous local trauma was recorded. The second case, a man with septic arthritis of right knee, had degenerative disease of the knees and a prostatic adenocarcinoma. In the third patient, a diabetic woman with septic arthritis of the left shoulder, vulvovaginitis due to Candida albicans was found. The last patient suffered vertebral osteomyelitis of the cervical spine (C3-C4), arthritis of the left sternoclavicular and hip joints and abscess of the ipsilateral psoas. The evolution was favourable in the four cases. CONCLUSIONS: Although uncommon, osteomyelitis and arthritis caused by group B streptococcus should be considered as opportunistic pathogen in adults with debilitating conditions. Early recognition and prompt institution of adequate therapy can help avoid joint destruction and severe complications.

Case report 866. Pseudotumor of the muscle associated with necrotizing vasculitis of medium- and small-sized arteries and chronic myositis.

A case of polymyositis and localized vasculitis presenting as a muscular pseudotumor of a lower extremity and periostitis several years after the onset of symptoms was reported and the MRI characteristics were described. This imaging modality demonstrated muscle signal abnormalities in several muscle groups and was useful in ruling out the presence of a mass and fatty degeneration of the muscle. The ability of the STIR sequence (Fig. 3D) to show muscle abnormalities and to allow fatty infiltration or degeneration to be ruled out has not been reported before in patients with vasculitic muscle involvement.

Clinical and pathologic studies of twenty-six patients with penetrating foreign body injury to the joints, bursae, and tendon sheaths.

Foreign body synovitis has been neglected in the rheumatology literature. We describe 26 patients in whom arthritis, bursitis, or tenosynovitis appeared within 1 day to 7 years after an initial injury by a penetrating foreign body. Twenty-two patients presented with acute synovitis, which was followed by chronic or recurrent inflammation mimicking septic arthritis, osteomyelitis, monarticular juvenile rheumatoid arthritis, bone tumor, or apatite deposition disease. Foreign bodies were not seen in 5 inflammatory synovial fluids studied, but were seen in the synovium or periarticular tissues of 17 patients. Excisional biopsy was required in most patients for precise diagnosis and treatment.

Tuberculous arthritis of peripheral joints in patients with previous inflammatory rheumatic disease.

Four patients with a previous inflammatory rheumatic disease developed a peripheral tuberculous (TB) arthritis in a joint apparently affected by a rheumatic disease. The single most important factor in the diagnosis of TB was the presence of past or present pulmonary TB or a family history on a background of steroid use. Clinical presentation, disease evolution, and routine laboratory tests were unhelpful. The most effective method of diagnosis was synovial biopsy.