Idiopathic intracranial hypertension secondary to fluoroquinolone therapy: French pharmacovigilance data review.

We investigate spontaneous reports of IIH related to fluoroquinolones recorded in the French national pharmacovigilance database in order to detect a possible pharmacovigilance signal. The association between IIH risk and fluoroquinolone exposure was assessed using a case/non-case study. Between 1985 and July 2023, 17 reports of IIH after fluoroquinolone exposure were recorded. No specific fluoroquinolone was predominant. IIH led to death in one case and blindness in one case. The Reporting Odds Ratio was 2.58 (95% confidence interval 1.59-4.19). We highlight statistically significant disproportionality, which constitutes a pharmacovigilance signal. IIH risk after fluoroquinolone exposure is a class effect.

Safety in Dermatologic Procedures: Ophthalmologic Complications. / Seguridad en procedimientos dermatológicos: complicaciones oftalmológicas.

Ophthalmological complications are uncommon in dermatologic surgery. Nonetheless, all surgeons should know the basics of recognizing, preventing, and treating the 4 complications addressed in this article from the series 'Safety in Dermatologic Procedures'. The first complication that surgeons should be familiar with is eye damage due to chemical irritants. This is a common complication in operating rooms given the presence of irritant substances and the performance of procedures in the eyebrow and eyelid region. The second complication is laser-induced eye damage. In this case, eye protection with safety glasses or eye caps is crucial. The third complication is accidental eyeball perforation, which can occur during certain surgical procedures. The fourth and final complication is retinal artery vasospasm or embolism due to drugs or filler materials. This complication is rare but important to recognize, as early treatment can prevent permanent blindness.

Carbon nanodot-based electrogenerated chemiluminescence biosensor for miRNA-21 detection.

A simple carbon nanodot-based electrogenerated chemiluminescence biosensor is described for sensitive and selective detection of microRNA-21 (miRNA-21), a biomarker of several pathologies including cardiovascular diseases (CVDs). The photoluminescent carbon nanodots (CNDs) were obtained using a new synthesis method, simply by treating tiger nut milk in a microwave reactor. The synthesis is environmentally friendly, simple, and efficient. The optical properties and morphological characteristics of the CNDs were exhaustively investigated, confirming that they have oxygen and nitrogen functional groups on their surfaces and exhibit excitation-dependent fluorescence emission, as well as photostability. They act as co-reactant agents in the anodic electrochemiluminescence (ECL) of [Ru(bpy)3]2+, producing different signals for the probe (single-stranded DNA) and the hybridized target (double-stranded DNA). These results paved the way for the development of a sensitive ECL biosensor for the detection of miRNA-21. This was developed by immobilization of a thiolated oligonucleotide, fully complementary to the miRNA-21 sequence, on the disposable gold electrode. The target miRNA-21 was hybridized with the probe on the electrode surface, and the hybridization was detected by the enhancement of the [Ru(bpy)3]2+/DNA ECL signal using CNDs. The biosensor shows a linear response to miRNA-21 concentration up to 100.0 pM with a detection limit of 0.721 fM. The method does not require complex labeling steps, and has a rapid response. It was successfully used to detect miRNA-21 directly in serum samples from heart failure patients without previous RNA extraction neither amplification process.

A decade of clinical development of PARP inhibitors in perspective.

Genomic instability is a hallmark of cancer, and often is the result of altered DNA repair capacities in tumour cells. DNA damage repair defects are common in different cancer types; these alterations can also induce tumour-specific vulnerabilities that can be exploited therapeutically. In 2009, a first-in-man clinical trial of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib clinically validated the synthetic lethal interaction between inhibition of PARP1, a key sensor of DNA damage, and BRCA1/BRCA2 deficiency. In this review, we summarize a decade of PARP inhibitor clinical development, a work that has resulted in the registration of several PARP inhibitors in breast (olaparib and talazoparib) and ovarian cancer (olaparib, niraparib and rucaparib, either alone or following platinum chemotherapy as maintenance therapy). Over the past 10 years, our knowledge on the mechanism of action of PARP inhibitor as well as how tumours become resistant has been extended, and we summarise this work here. We also discuss opportunities for expanding the precision medicine approach with PARP inhibitors, identifying a wider population who could benefit from this drug class. This includes developing and validating better predictive biomarkers for patient stratification, mainly based on homologous recombination defects beyond BRCA1/BRCA2 mutations, identifying DNA repair deficient tumours in other cancer types such as prostate or pancreatic cancer, or by designing combination therapies with PARP inhibitors.

RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer.

Background: BRCA1 and BRCA2 (BRCA1/2)-deficient tumors display impaired homologous recombination repair (HRR) and enhanced sensitivity to DNA damaging agents or to poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). Their efficacy in germline BRCA1/2 (gBRCA1/2)-mutated metastatic breast cancers has been recently confirmed in clinical trials. Numerous mechanisms of PARPi resistance have been described, whose clinical relevance in gBRCA-mutated breast cancer is unknown. This highlights the need to identify functional biomarkers to better predict PARPi sensitivity. Patients and methods: We investigated the in vivo mechanisms of PARPi resistance in gBRCA1 patient-derived tumor xenografts (PDXs) exhibiting differential response to PARPi. Analysis included exome sequencing and immunostaining of DNA damage response proteins to functionally evaluate HRR. Findings were validated in a retrospective sample set from gBRCA1/2-cancer patients treated with PARPi. Results: RAD51 nuclear foci, a surrogate marker of HRR functionality, were the only common feature in PDX and patient samples with primary or acquired PARPi resistance. Consistently, low RAD51 was associated with objective response to PARPi. Evaluation of the RAD51 biomarker in untreated tumors was feasible due to endogenous DNA damage. In PARPi-resistant gBRCA1 PDXs, genetic analysis found no in-frame secondary mutations, but BRCA1 hypomorphic proteins in 60% of the models, TP53BP1-loss in 20% and RAD51-amplification in one sample, none mutually exclusive. Conversely, one of three PARPi-resistant gBRCA2 tumors displayed BRCA2 restoration by exome sequencing. In PDXs, PARPi resistance could be reverted upon combination of a PARPi with an ataxia-telangiectasia mutated (ATM) inhibitor. Conclusion: Detection of RAD51 foci in gBRCA tumors correlates with PARPi resistance regardless of the underlying mechanism restoring HRR function. This is a promising biomarker to be used in the clinic to better select patients for PARPi therapy. Our study also supports the clinical development of PARPi combinations such as those with ATM inhibitors.

IVIVC approach based on carbamazepine bioequivalence studies combination.

The aim of the present study was to explore the feasibility of obtaining an IVIVC by combination of data from two bioequivalence (BE) studies of carbamazepine (CBZ) in order to assess if the previously published dissolution media and conditions could be applicable to any other oral immediate release (IR) CBZ products with conventional excipients. Twenty-four healthy male subjects from two BE study received one IR dose of the test (test 1 or 2) or the reference formulation (Tegretol, 400 mg). Dissolution studies of the IR CBZ tablets were performed in two different laboratories. In order to develop IVIVC, individual or average data analysis were considered. A level C, level B and level A correlation have been successfully developed by combining data from different BE studies of CBZ immediate release drug products. A level A IVIVC was developed with all four datasets with a good R2 for all the combinations of in vivo and in vitro data. A dissolution medium containing 1% SLS has demonstrated its suitability as the universal biopredictive dissolution medium, even if different batches and in vivo/in vitro studies were combined.

Increased expression of the dopamine transporter leads to loss of dopamine neurons, oxidative stress and l-DOPA reversible motor deficits.

The dopamine transporter is a key protein responsible for regulating dopamine homeostasis. Its function is to transport dopamine from the extracellular space into the presynaptic neuron. Studies have suggested that accumulation of dopamine in the cytosol can trigger oxidative stress and neurotoxicity. Previously, ectopic expression of the dopamine transporter was shown to cause damage in non-dopaminergic neurons due to their inability to handle cytosolic dopamine. However, it is unknown whether increasing dopamine transporter activity will be detrimental to dopamine neurons that are inherently capable of storing and degrading dopamine. To address this issue, we characterized transgenic mice that over-express the dopamine transporter selectively in dopamine neurons. We report that dopamine transporter over-expressing (DAT-tg) mice display spontaneous loss of midbrain dopamine neurons that is accompanied by increases in oxidative stress markers, 5-S-cysteinyl-dopamine and 5-S-cysteinyl-DOPAC. In addition, metabolite-to-dopamine ratios are increased and VMAT2 protein expression is decreased in the striatum of these animals. Furthermore, DAT-tg mice also show fine motor deficits on challenging beam traversal that are reversed with l-DOPA treatment. Collectively, our findings demonstrate that even in neurons that routinely handle dopamine, increased uptake of this neurotransmitter through the dopamine transporter results in oxidative damage, neuronal loss and l-DOPA reversible motor deficits. In addition, DAT over-expressing animals are highly sensitive to MPTP-induced neurotoxicity. The effects of increased dopamine uptake in these transgenic mice could shed light on the unique vulnerability of dopamine neurons in Parkinson's disease.

N-terminal tagging of the dopamine transporter impairs protein expression and trafficking in vivo.

The dopamine transporter (DAT) is the primary protein responsible for the uptake of dopamine from the extracellular space back into presynaptic neurons. As such, it plays an important role in the cessation of dopaminergic neurotransmission and in the maintenance of extracellular dopamine homeostasis. Here, we report the development of a new BAC transgenic mouse line that expresses DAT with an N-terminal HA-epitope (HAD-Tg). In this line, two copies of the HA-DAT BAC are incorporated into the genome, increasing DAT mRNA levels by 47%. Despite the increase in mRNA levels, HAD-Tg mice show no significant increase in the level of DAT protein in the striatum, indicating a defect in protein trafficking or stability. By crossing HAD-Tg mice with DAT knockout mice (DAT-KO), we engineered mice that exclusively express HA-tagged DAT in the absence of endogenous DAT (DAT-KO/HAD-Tg). We show that DAT-KO/HAD-Tg mice express only 8.5% of WT DAT levels in the striatum. Importantly, the HA-tagged DAT that is present in DAT-KO/HAD-Tg mice is functional, as it is able to partially rescue the DAT-KO hyperactive phenotype. Finally, we provide evidence that the HA-tagged DAT is retained in the cell body based on a reduction in the striatum:midbrain protein ratio. These results demonstrate that the presence of the N-terminal tag leads to impaired DAT protein expression in vivo due in part to improper trafficking of the tagged transporter, and highlight the importance of the N-terminus in the transport of DAT to striatal terminals.

Third-line rescue therapy with bismuth-containing quadruple regimen after failure of two treatments (with clarithromycin and levofloxacin) for H. pylori infection.

BACKGROUND: Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin fails in >20 % of cases. A rescue therapy with PPI-amoxicillin-levofloxacin still fails in >20 % of patients. AIM: To evaluate the efficacy and tolerability of a bismuth-containing quadruple regimen in patients with two consecutive eradication failures. METHODS: Prospective multicenter study of patients in whom 1st treatment with PPI-clarithromycin-amoxicillin and 2nd with PPI-amoxicillin-levofloxacin had failed. A 3rd eradication regimen with a 7- to 14-day PPI (standard dose b.i.d.), bismuth subcitrate (120 mg q.i.d. or 240 mg b.i.d.), tetracycline (from 250 mg t.i.d. to 500 mg q.i.d.) and metronidazole (from 250 mg t.i.d. to 500 mg q.i.d.). Eradication was confirmed by (13)C-urea-breath-test 4-8 weeks after therapy. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by means of a questionnaire. RESULTS: Two hundred patients (mean age 50 years, 55 % females, 20 % peptic ulcer/80 % uninvestigated-functional dyspepsia) were initially included, and two were lost to follow-up. In all, 97 % of patients complied with the protocol. Per-protocol and intention-to-treat eradication rates were 67 % (95 % CI 60-74 %) and 65 % (58-72 %). Adverse effects were reported in 22 % of patients, the most common being nausea (12 %), abdominal pain (11 %), metallic taste (8.5 %), and diarrhea (8 %), none of them severe. CONCLUSION: A bismuth-containing quadruple regimen is an acceptable third-line strategy and a safe alternative after two previous H. pylori eradication failures with standard clarithromycin- and levofloxacin-containing triple therapies.

[Self-assessment of patterns of antibiotic use in a university hospital]. / Autovaloración sobre prescripción de antibióticos en un hospital universitario.

INTRODUCTION: A questionnaire was used to determine the knowledge, attitudes and practices of antibiotic prescribing among doctors at a university hospital. METHODS: An anonymous questionnaire was directly distributed by a staff member of the Infectious Diseases Department. RESULTS: A total of 316 questionnaires were distributed with 100% response rate; antibiotic dose, route of administration, and treatment duration were always adjusted according to site of infection and underlying conditions in 65, 68 and 45%, respectively. Antibiotic de-escalation was recognized as usual practice in 20%; 31 and 10% considered potential microbiological resistances and economical-cost when taking prescription decisions, respectively; 16% admitted often prescribing antibiotics with no clinical indication. There were no major significant differences between staff and training physicians, or between surgical or medical specialists. CONCLUSIONS: The self-perception of physicians and residents in our hospital is that they make improper use of antimicrobials.

New mathematical model from dynamic dissolution rate tests.

In vitro dissolution experiments are becoming increasingly complex attempting to replicate in vivo behavior. The objective of these new methods is to explore the behavior of low-solubility drugs. This is more relevant for drugs classified in subclasses 2a, 2b and 2c of the BCS, considering their pH-dependent solubility and dissolution characteristics. A novel mathematical approach using a modified double Weibull equation is proposed to model the dissolution and precipitation kinetics observed in two-stage and transfer dissolution experiments (dumping test). This approach demonstrates a high level of accuracy in fitting experimental data for two drugs BCS class 2a and two BCS class 2b, providing valuable insights into their dissolution behavior under different conditions. The results highlight the versatility of the proposed model in capturing complex dissolution phenomena, including rapid dissolution, precipitation, and redissolution. The ease of implementation in Excel, using the Solver tool, makes it a practical and accessible tool for pharmaceutical researchers. Overall, the study contributes to the development of more effective in vitro dissolution testing methods, facilitating the formulation and optimization of pharmaceutical products and potentially aiding in the establishment of in vitro-in vivo correlations (IVIVC).

Imaging findings of the postoperative chest: What the radiologist should know.

Thoracic surgical procedures are increasing in recent years, and there are different types of lung resections. Postsurgical complications vary depending on the type of resection and the time elapsed, with imaging techniques being key in the postoperative follow-up. Multidisciplinary management of these patients throughout the perioperative period is essential to ensure an optimal surgical outcome. This pictorial review will review the different thoracic surgical techniques, normal postoperative findings and postsurgical complications.

Mathematical modeling of oral absorption and bioavailability of a fluoroquinolone after its precipitation in the gastrointestinal tract.

The objective was to characterize the in vivo absorption and bioavailability (BA) of a low solubility, high permeability fluoroquinolone (CNV97101) that precipitates in the gastrointestinal (GI) tract by mathematical modeling approach. In situ rat intestinal perfusion studies were performed to characterize the absorption mechanism. The oral fraction absorbed in vivo was lower than the predicted based on the in situ intestinal permeability. Two additional routes of administration, intraduodenal (ID) and intraperitoneal (IP) were investigated to explore if precipitation in stomach and subsequent partial re-dissolution were the causes of the lower in vivo BA. Ex vivo precipitation studies with the stomach content of fasted rats were also carried out. Fitting procedures were performed with NONMEM VII 1.2. The in situ experiments confirmed simultaneous passive and carrier-mediated absorption processes. The ex vivo experiments confirmed precipitation in stomach lowering in vivo the oral fraction absorbed compared with the IP and ID administrations. Due to the almost complete availability of CNV97101 following IP administration, a first hepatic pass could be excluded. The ex vivo assay results and the pharmacokinetic modeling of in vivo data supported the hypothesis of precipitation in the stomach and partial re-dissolution. Nevertheless, other factors such as residence time in the GI may reduce the fraction absorbed even for low oral doses for which re-dissolution was almost complete in vivo.

[Uveitis: Study of 109 cases]. / Uveítis: estudio de 109 casos.

PURPOSE: Analyse and describe the anatomical and etiological classification, clinical and epidemiological characteristics and most frequent symptoms of uveitis cases in our population. PATIENTS AND METHOD: Descriptive, retrospective observational study of uveitis cases treated in the Ophthalmology Department of Virgen del Rocío University Hospital in 2021. The demographic and clinical characteristics were studied. RESULTS: A total of 109cases of uveitis were studied, 46 men and 63 women, with a mean age of 45.43±16.11 years. The most frequent symptoms were pain (74.31%), hyperemia (73.39%) and blurred vision (65.14%). The most frequent anatomical classification was anterior (55.96%), followed by panuveitis (18.35%), posterior (12.84%) and intermediate uveitis (7.34%). Regarding etiology, most uveitis were idiopathic (42.99%), followed by non-infectious (38.32%) and finally infectious (18.69%). CONCLUSIONS: In southern España, the characteristics of uveitis are similar to other studies in Western countries.

[Ultrasound-guided longitudinal tenotomy for plantar fasciitis. Technical note and systematic review]. / Tenotomía longitudinal ecoguiada para el tratamiento de fascitis plantar. Nota técnica y revisión sistemática.

INTRODUCTION: plantar fasciitis or fasciosis is a cause of foot pain with cases resistant to conservative treatment. Surgery is reserved for patients who have not responded to conservative treatment, shock waves, or corticosteroid injections. The aim of this publications is to carry out a systematic review of the available literature and to describe a specific technique for the treatment of plantar fasciosis consisting of the longitudinal tearing of the plantar aponeurosis assisted with ultrasound. MATERIAL AND METHODS: a systematic search was carried out for previous publications on longitudinal tenotomy in the treatment of plantar fasciitis. The Medical Subject Headings (MeSH) terms "Curettage", "Tenotomy" and "Plantar Fasciitis" were included. The electronic search included PubMed, Embase, Cochrane central register of controlled trials, Trip database, and National Institute for Health and Care Excellence (NICE) databases. A detailed description of the technique was included with the intention that it can be reproduced. CONCLUSION: longitudinal tenotomy represents an alternative for the treatment of plantar fasciitis. It is based on the extrapolation of knowledge in the Achilles tendon territory with a supporting pathophysiological basis. It is a non-invasive technique that can be performed on an outpatient basis and that would allow the rapid incorporation of the patient to their activities. Longitudinal tenotomy would prevent the patient from undergoing major surgeries.

INTRODUCCIÓN: la fascitis o fasciosis plantar es una causa de dolor en el pie, en la cual frecuentemente se encuentran casos resistentes al tratamiento conservador. La cirugía queda reservada para los pacientes que no han respondido a tratamientos conservadores, ondas de choque o infiltraciones con corticosteroides. El objetivo de este trabajo es realizar una revisión sistemática de la literatura disponible y describir una técnica para el tratamiento de la fascitis o fasciosis plantar consistente en el rasgado longitudinal de la aponeurosis plantar asistido con ecografía. MATERIAL Y MÉTODOS: se realizó una búsqueda sistemática de publicaciones previas sobre la tenotomía longitudinal en el tratamiento de la fascitis plantar. Se incluyeron los encabezados de temas médicos o MeSH (Medical subjects headings por sus siglas en inglés), en inglés: Curettage, Tenotomy y Plantar Fasciitis. La búsqueda electrónica incluyó las bases de datos de PubMed, Embase, Cochrane central register of controlled trials, Trip database y National Institute for Health and Care Excellence (NICE por sus siglas en inglés). Se realizó una descripción detallada de la técnica con la intención de que pueda ser reproducida. CONCLUSIÓN: la tenotomía longitudinal representa una alternativa para el tratamiento de la fascitis plantar. Se basa en la extrapolación del conocimiento en el territorio Aquíleo con una base fisiopatológica de respaldo. Se trata de una técnica no invasiva que se puede realizar de forma ambulatoria y que permitiría la rápida incorporación del paciente a sus actividades. La tenotomía longitudinal podría evitar al paciente someterse a cirugías de mayor envergadura.

[Effects of home-based strength training during COVID-19 lockdown in acute coronary syndrome]. / Efectos del entrenamiento de fuerza domiciliario durante el confinamiento por COVID-19 en el síndrome coronario agudo.

INTRODUCTION AND OBJECTIVE: Cardiac rehabilitation has the highest level of recognition in medical guideline references. The rise of COVID-19 pandemic, particularly during the first months of strict containment, cause to temporally stop most of the ongoing programs. We studied the effects of an interdisciplinary phase II secondary prevention in patients diagnosed with a recent acute coronary syndrome with the use of new technologies, home-exercise and telemedicine. METHODS: Between the 2nd and 11th of March 2020, we included 37 patients with recent acute coronary syndrome (76.4%), low-risk and preserved systolic function and underwent a 12-week treatment. A dynamic muscle toning with overload domiciliary training program was applied, in addition to nutritional counselling, as well as psychological and educational therapy. RESULTS: Of the initial cohort, 30 patients finished. At the end of the program, we observed and increased functional capacity over the 6-min walking test (+47.13m; 95% CI: 32.82-61.45, P<.001), and improvement to the subjective feeling of dyspnoea on the modified Borg scale (-0.5 units; 95% CI: -0.76 to -0.24, P=.001), and an improvement over both initial and final training systolic blood pressure (-6.67mmHg; 95% CI: -10.98 to -2.35, P=.004) (-7mmHg; 95% CI: -12.86 to -1.14, P=.021). We also observed an increase in the level of physical activity during leisure time in the IPAQ questionnaire (+1162.93min/week; 95% CI: 237.36-2088.5, P=.016), and in the Mediterranean eating habits on the PREDIMED test (+2.1units; 95% CI: 1.32-2.28, P<.001). CONCLUSIONS: After three months of a domiciliary cardiac rehabilitation program, patients increased their functional capacity, feeling of dyspnoea, blood pressure and eating habits. Domiciliary telemedicine cardiac rehabilitation program produces an improvement in the patient after acute coronary syndrome.

Level A IVIVC for immediate release tablets confirms in vivo predictive dissolution testing for ibuprofen.

A bioequivalence study comparing two fixed dose combination tablets containing 200 mg ibuprofen and 30 mg pseudoephedrine hydrochloride showed bioequivalence for pseudoephedrine AUC and Cmax, but the reference product showed higher Cmax than the test product in fasted conditions. The main difference between products was the presence of tribasic calcium phosphate in the reference tablet, resulting in an increased surface pH of the dissolving ibuprofen particles under gastric and intestinal conditions and, consequently, higher solubility of ibuprofen. A mechanistic model based on mass balance and ionization equilibria was used to calculate the pH of the particle surface under different buffer conditions. The discrepancies in surface pH between test and reference tablet were pronounced in 0.1 M and 0.01 M hydrochloric acid and in diluted maleate 7 mM pH 6.5 and phosphate 5 mM pH 6.7 buffers (but negligible in compendial phosphate buffer pH 6.8. Only those dissolution tests using pre-treatment in acidic conditions could be used to build a one-step in vitro-in vivo correlation (IVIVC). This work shows the potential of these discriminatory and in vivo predictive dissolution methods to obtain IVIVCs for BCS class IIa drugs and for extending BCS biowaivers to BCS class IIa drugs.

Association between neuroimaging findings and neurological sequelae in patients with congenital cytomegalovirus infection.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is an important cause of disability. There is little evidence on the prognostic value of lesions identified in neuroimaging studies. AIM: The study aimed to assess the severity of lesions detected with brain MRI and transfontanellar ultrasound and their relationship with long-term neurological deficits. PATIENTS AND METHODS: We performed a retrospective, analytical, observational study of 36 patients with congenital CMV infection. Neuroimaging studies were reviewed and classified according to the modified Noyola' scale. Imaging findings were compared with neurological alterations in the patients' most recent follow-up evaluation at the paediatric neurology department. RESULTS: Thirty-six patients were studied (transfontanellar ultrasound: 30; brain MRI: 29). Twenty of 30 patients showed ultrasound abnormalities; of these, 11 showed alterations on brain MR images (P = .04) and 10 had neurological impairment (P = .008). Transfontanellar ultrasound had a sensitivity of 83.3%, 90% CI: 58-100 and a specificity of 44.4%, 90% CI: 18.7-70.2 for predicting neurological sequelae. Brain MRI displayed abnormalities in 20 of 29 patients, of whom 16 had neurological impairment (P < .001). MRI had a sensitivity of 94%, 95% CI: 80-100 and a specificity of 66.6%, 95% CI: 36-97.5 for predicting neurological sequelae. Modified Noyola' scale values > 2 were correlated with psychomotor retardation (P < .001). CONCLUSIONS: Our findings validate previous studies reporting a statistical significant correlation between the extension of neuroimaging lesions and severity of neurological deficits.

[Effects of an interdisciplinary program combining aerobic interval training and dynamic strength in acute coronary syndrome]. / Efectos de un programa interdisciplinar combinado con entrenamiento aeróbico continuo variable y fuerza dinámica en el síndrome coronario agudo.

INTRODUCTION AND OBJECTIVES: Cardiac rehabilitation has the highest level of recognition in medical guideline references, however there are still little-explored training modalities. We study the effects of an interdisciplinary program after acute coronary syndrome (ACS) in phase II secondary prevention. METHODS: Between January 2008 and December 2018, 439 patients with stable ischemic heart disease and preserved systolic function were included, as maximum 2 month after the ACS. A combined aerobic resistance training program in a variable continuous method and muscle toning with overload and/or ballast was applied, in addition to nutritional counseling and psychological-educational therapy for 12 weeks. RESULTS: 378 patients finished. The functional capacity increases in the incremental stress test (1.76 METS; CI 95%: 1.59-1.96, p < 0.001) and in the six minutes walking test (32.58 m; CI 95%: 29.24-35.92, p < 0.001). Leisure physical activity in IPAQ increased (763.27 min/week; CI 95%: 583.31-943.16, p < 0.001) and the time sitting during the week decreased (-28.85 min/day; CI 95%: -43.94 to -13.77, p < 0.001). Also, eating habits improved in PREDIMED (2.58 units; CI 95%: 1.43-3.73, p < 0.001), decreased body weight (-0.88 kg; CI 95%: -1.26 to -0.49, p < 0.001), the abdominal perimeter (1.57 cm; CI 95%: 2.23-0.90, p < 0.001) and adipose tissue (-0.80%; CI 95%: -1.10 to -0.51, p < 0.001). CONCLUSIONS: An interdisciplinary program with high intensity variable continuous training combined with dynamic muscle toning increases functional capacity, the level of physical activity, improves body composition and eating habits in ACS patients.

[Propranolol for the treatment of severe hemangiomas of infancy: results from a series of 28 patients]. / Tratamiento con propranolol oral para hemangiomas infantiles graves: serie de 28 pacientes.

BACKGROUND AND OBJECTIVES: Recent reports have described the successful use of propranolol to treat severe hemangiomas of infancy. The few case series that have been reported, however, have included only a small number of patients. The aim of this study was to describe the results of oral propranolol treatment for severe hemangiomas of infancy in terms of treatment outcome and the occurrence of adverse events. PATIENTS AND METHODS: A descriptive, observational study was undertaken in a series of children with severe hemangiomas of infancy seen in the pediatric dermatology unit at Hospital Universitario Virgen del Rocío in Seville, Spain between July 2008 and December 2009. Patients were included if they had hemangiomas in the proliferative phase or involuting lesions with substantial residual deformity. All children were treated with oral propranolol (2 mg/kg/d) and followed until September 2010. Epidemiologic characteristics were analyzed along with treatment response at 3, 6, 9, 12, and 18 months; adverse events were also recorded at those times. RESULTS: Thirty-six hemangiomas were treated in 28 patients. Propranolol treatment was effective in all cases, with a good or complete response in 88.2% at 6 months. Effects were apparent within a few hours of treatment, which was effective in both growing and involuting hemangiomas. In ulcerated hemangiomas, the mean healing time was 61 days. Adverse events were mild and self-limiting. Only 2 patients discontinued treatment due to hypotension. CONCLUSIONS: In the majority of cases, oral propranolol produced rapid and sustained improvements in hemangiomas of infancy and shortened the natural course of the disease with few side effects. However, no significant reductions in symptoms or healing time were observed in ulcerated hemangiomas.