The matter of "unbalance" in right dominant atrioventricular septal defect.

Unbalance in atrioventricular septal defect can be found in more than one anatomic level and in different degrees at each level. The definition of "unbalance" has historically been focused in comparing the dimensions of main cardiac structures, such as the atrioventricular valve and the ventricles. However, the hemodynamic aspects of unbalance need to be considered as having, at least, similar relevance. New concepts and already described parameters must be combined and understood as a whole to help the surgical decision-making process.

Subcutaneous bortezomib in newly diagnosed patients with multiple myeloma nontransplant eligible: Retrospective evaluation.

Bortezomib-melphalan-prednisone combination is one of the standards of care for nontransplant eligible patients with newly diagnosed multiple myeloma. However, bortezomib intravenous (twice weekly for 4 cycles then weekly for 5 cycles) results in ~13% of patients with grade 3-4 peripheral neuropathy. Bortezomib subcutaneous (SQ) and weekly delivery, improves tolerability without impairment of efficacy. The aim of this study was to evaluate the safety and effectiveness of SQ bortezomib-based combinations in nontransplant eligible patients with newly diagnosed myeloma in a real-world setting. A total of 135 patients (median age [range] = 76 [58-89], International Staging System-III = 54%, median follow-up = 14.8 months [1-40], Intensive group [twice weekly bortezomib] = 65%, Optimized group [weekly bortezomib] = 35%) were included and evaluable for safety, whereas 121 were evaluable for effectiveness. Overall response rate (95% CI) was 61% (53%, 71%) (complete response = 27%, very good partial response = 13%, and partial response = 21%) and median progression-free survival was 22.2 months (95% CI: 16.1-not reached). The 3-year overall survival was 75%. The most frequent grade 3-4 adverse events were thrombocytopenia (18%), neutropenia (17%), and anemia (11%). Peripheral neuropathy of any grade was observed in 44% of patients (2% with grade 3). Comparison between regimens (Intensive vs Optimized) showed similar overall response rate (57% vs 70%) and PFS (25 vs 19 months). A similar safety profile was observed between regimens. Thus, SQ bortezomib showed similar effectiveness and better tolerability as compared with results from intravenous bortezomib studies, and showing no differences either in effectiveness or safety in different bortezomib-based combinations.

MULTI-CRITERIA DECISION ANALYSIS AS A DECISION-SUPPORT TOOL FOR DRUG EVALUATION: A PILOT STUDY IN A PHARMACY AND THERAPEUTICS COMMITTEE SETTING.

OBJECTIVES: The aim of this study was to develop and to assess a specific Multi-Criteria Decision Analysis (MCDA) framework to evaluate new drugs in an hospital pharmacy and therapeutics committee (P&TC) setting. METHODS: A pilot criteria framework was developed based on the EVIDEM (Evidence and Value: Impact on DEcisionMaking) framework, together with other relevant criteria, and assessed by a group of P&TC's members. The weighting of included criteria was done using a 5-point weighting technique. Two drugs were chosen by evaluation: an orphan-drug for Gaucher disease, and a nonorphan drug for the treatment of inflammatory bowel disease. Evidence matrices were developed, and value contribution of each drug was evaluated by P&TC's members. An agreed final framework was obtained through a discussion between the P&TC's members. RESULTS: After criteria assessment, the pilot framework included eight quantitative criteria: "disease severity," "unmet needs," "comparative efficacy/effectiveness," "comparative safety/tolerability," "comparative patient-reported outcomes," "comparative cost consequences-cost of treatment," "comparative cost consequences-other medical costs," and "quality of evidence"; and one contextual criterion: "opportunity costs and affordability." The most valued criteria were: "comparative safety/tolerability," "disease severity," and "comparative efficacy/effectiveness." When assessing the drugs most valued characteristics of the MCDA were the possibility that all team may contribute to drug assessment by means of scoring the matrices and the discussion to reach a consensus in drug positioning and value decision making. CONCLUSIONS: The reflective MCDA would integrate quantitative and qualitative criteria relevant for a P&TC setting, allowing reflective discussions based on the criteria weighting score.

Hipertensión pulmonar asociada al virus de la inmunodeficiencia humana en pediatría: tratamiento con sildenafil. A propósito de un caso / Pulmonary hypertension associated with the human immunodeficiency virus in children: treatment with sildenafil. A case report

La hipertensión pulmonar asociada a la infección por virus de inmunodeficiencia humana es una enfermedad sumamente infrecuente en pediatría, por lo que requiere alta sospecha clínica para llegar a su diagnóstico. Su aparición es de pronóstico desfavorable, pero el diagnóstico precoz y el tratamiento específico pueden mejorar su evolución. Se presenta el caso clínico de un paciente de 15 años con diagnóstico de infección por virus de inmunodeficiencia humana de transmisión vertical, sin tratamiento antirretroviral, con tos y disnea de esfuerzo progresiva asociadas a signos de falla cardíaca derecha en el cual se diagnosticó hipertensión pulmonar grave. Luego de descartarse otras causas, se asumió la hipertensión pulmonar asociada a la infección por virus de inmunodeficiencia humana. Se realizó el tratamiento con sildenafil y presentó buena respuesta.

Pulmonary hypertension associated with human immunodeficiency virus infection is an extremely rare disease in pediatrics; it requires a high clinical suspicion to reach a diagnosis. Its appearance poses an unfavorable prognostic, but early diagnosis and specific treatment can improve outcomes. We report the clinical case of a fifteen-year-old patient diagnosed with human immunodeficiency virus infection of vertical transmission, without antiretroviral treatment, with cough and progressive exertional dyspnea, associated with signs of right heart failure in which severe pulmonary hypertension was diagnosed. After discarding other causes, it was assumed pulmonary hypertension associated with human immunodeficiency virus infection. Treatment was performed with sildenafil with good response.

[Pulmonary hypertension associated with the human immunodeficiency virus in children: treatment with sildenafil. A case report]. / Hipertensión pulmonar asociada al virus de la inmunodeficiencia humana en pediatría: tratamiento con sildenafil. A propósito de un caso.

Pulmonary hypertension associated with human immunodeficiency virus infection is an extremely rare disease in pediatrics; it requires a high clinical suspicion to reach a diagnosis. Its appearance poses an unfavorable prognostic, but early diagnosis and specific treatment can improve outcomes. We report the clinical case of a fifteen-year-old patient diagnosed with human immunodeficiency virus infection of vertical transmission, without antiretroviral treatment, with cough and progressive exertional dyspnea, associated with signs of right heart failure in which severe pulmonary hypertension was diagnosed. After discarding other causes, it was assumed pulmonary hypertension associated with human immunodeficiency virus infection. Treatment was performed with sildenafil with good response.

La hipertensión pulmonar asociada a la infección por virus de inmunodeficiencia humana es una enfermedad sumamente infrecuente en pediatría, por lo que requiere alta sospecha clínica para llegar a su diagnóstico. Su aparición es de pronóstico desfavorable, pero el diagnóstico precoz y el tratamiento específico pueden mejorar su evolución. Se presenta el caso clínico de un paciente de 15 años con diagnóstico de infección por virus de inmunodeficiencia humana de transmisión vertical, sin tratamiento antirretroviral, con tos y disnea de esfuerzo progresiva asociadas a signos de falla cardíaca derecha en el cual se diagnosticó hipertensión pulmonar grave. Luego de descartarse otras causas, se asumió la hipertensión pulmonar asociada a la infección por virus de inmunodeficiencia humana. Se realizó el tratamiento con sildenafil y presentó buena respuesta.

Modified In Situ Pericardial Rerouting Technique for Scimitar Syndrome Repair.

Scimitar syndrome repair represents a challenge due to the high incidence of postoperative pulmonary venous obstruction associated with classic surgical strategies. In situ pericardial rerouting technique has been considered a promising alternative approach due to its simplicity and excellent midterm results. Access to the left atrium can be difficult in young patients with severe dextrocardia and hypoplastic right lung. We describe a modification of the original rerouting technique in which the atrial septum is repositioned in order to create a wide opening in the lateral aspect of the left atrium and ensure an adequate size of the reconstructed pathway.

Feasibility of Biventricular Repair in Right Dominant Unbalanced Atrioventricular Septal Defect: A New Echocardiographic Metric to Refine Surgical Decision-Making.

BACKGROUND: Unbalanced forms of atrioventricular septal defect continue to be challenging and present poor surgical outcomes. Echocardiographic indicators such as atrioventricular valve index, right ventricle/left ventricle inflow angle, and size of the ventricular septal defect have been identified as relevant discriminators that may guide surgical strategy. Our purpose is to describe another metric to refine surgical decision-making. METHODS: We outline a geometrical description of the anatomic features of atrioventricular septal defect and describe equations that help explain the interplay between the main echocardiographic variables. RESULTS: A new metric called "indexed ventricular septal defect" is defined as the size of the defect in relation to the valve diameter. We derive a final equation relating this index with the atrioventricular valve index and the right ventricle/left ventricle inflow angle. In the light of that equation, we discuss the interdependence of variables and employ data from a Congenital Heart Surgeons' Society study to set the limits of the new index. CONCLUSION: Combined use of indexed ventricular septal defect and atrioventricular valve index might help clarify surgical decision-making in patients with mild and moderate unbalance (modified atrioventricular valve index between 0.2 and 0.39). For indexed ventricular septal defect smaller than 0.2, biventricular repair may be recommended. Between 0.2 and 0.35, this strategy could probably be achieved depending on other factors. However, other strategies should be considered for those patients showing an indexed ventricular septal defect between 0.35 and 0.5. For values above 0.5 to 0.55, univentricular palliation might be a reasonable strategy.

Evaluation of tolerability and efficacy of imatinib mesylate in elderly patients with chronic phase CML: ELDERGLI study.

Imatinib mesylate (IM) is the treatment of choice in patients with newly diagnosed chronic myeloid leukemia (CML), irrespectively of their age. Nevertheless, information regarding tolerability and responses in advanced-age patients, a subgroup in which co-morbidities and other factors may influence outcome, is scarce, since they were excluded from most clinical trials. In this observational study (ELDERGLI), information regarding demographics, concomitant medication, physical examination, performance status, hemogram, biochemistry, hematologic, cytogenetic and molecular responses, time to progression, adverse events (AE) and severe adverse events (SAE) were prospectively recorded in a series of 36 elderly patients with CML, with a median age of 76.6 years. Most patients had cardiovascular co-morbidities, especially hypertension. Regarding IM toxicity, around one third of patients required treatment interruptions because of adverse events, especially hematologic toxicity (66% of cases that needed dose interruptions). When analyzing non hematologic adverse events, the most frequent ones were superficial edemas and GI symptoms. Of note, 9 of patients experienced an infection episode during the follow-up, and 4 were diagnosed during the study period of another type of cancer. Finally, cardiovascular events were reported in 7 patients, most of them with prior cardiovascular risk factors. Regarding responses, after 12 months of imatinib therapy, the rate of complete hematologic response (CHR), complete cytogenetic response (CCyR) and major molecular response (MMolR) were 89%, 72% and 55% respectively. In summary, IM display, in advanced-age patients with chronic phase CML, an efficacy and safety profile comparable to younger patients.

Mitochondrial superoxide dismutase and glutathione peroxidase in idiosyncratic drug-induced liver injury.

UNLABELLED: Drug-induced liver injury (DILI) susceptibility has a potential genetic basis. We have evaluated possible associations between the risk of developing DILI and common genetic variants of the manganese superoxide dismutase (SOD2 Val16Ala) and glutathione peroxidase (GPX1 Pro200Leu) genes, which are involved in mitochondrial oxidative stress management. Genomic DNA from 185 DILI patients assessed by the Council for International Organizations of Medical Science scale and 270 sex- and age-matched controls were analyzed. The SOD2 and GPX1 genotyping was performed using polymerase chain reaction restriction fragment length polymorphism and TaqMan probed quantitative polymerase chain reaction, respectively. The statistical power to detect the effect of variant alleles with the observed odds ratio (OR) was 98.2% and 99.7% for bilateral association of SOD2 and GPX1, respectively. The SOD2 Ala/Ala genotype was associated with cholestatic/mixed damage (OR = 2.3; 95% confidence interval [CI] = 1.4-3.8; corrected P [Pc] = 0.0058), whereas the GPX1 Leu/Leu genotype was associated with cholestatic injury (OR = 5.1; 95%CI = 1.6-16.0; Pc = 0.0112). The presence of two or more combined risk alleles (SOD2 Ala and GPX1 Leu) was more frequent in DILI patients (OR = 2.1; 95%CI = 1.4-3.0; Pc = 0.0006). Patients with cholestatic/mixed injury induced by mitochondria hazardous drugs were more prone to have the SOD2 Ala/Ala genotype (OR = 3.6; 95%CI = 1.4-9.3; Pc = 0.02). This genotype was also more frequent in cholestatic/mixed DILI induced by pharmaceuticals producing quinone-like or epoxide metabolites (OR = 3.0; 95%CI = 1.7-5.5; Pc = 0.0008) and S-oxides, diazines, nitroanion radicals, or iminium ions (OR = 16.0; 95%CI = 1.8-146.1; Pc = 0.009). CONCLUSION: Patients homozygous for the SOD2 Ala allele and the GPX1 Leu allele are at higher risk of developing cholestatic DILI. SOD2 Ala homozygotes may be more prone to suffer DILI from drugs that are mitochondria hazardous or produce reactive intermediates.

Exclusión interna: la percepción en la entrevista médica / Internal exclusion: the perception during the medical interview

Introducción. La entrevista predonación es un momento clave en la selección del donante donde la habilidad del entrevistador debe ir más allá del mero conocimiento de las normativas. Al realizarse la entrevista, deben desarrollarse otras capacidades que permitan lograr cierta empatía con el posible donante, tratando de percibir a través de gestos, palabras, miradas, posturas, y tonos de voz (comunicación analógica), si hay alguna disociación con la comunicación verbal (comunicación digital). Método. Se realizó una investigación sobre la serología reactiva y la autoexclusión de donantes cuyas unidades fueron descartadas por exclusión interna, que habiendo pasado la entrevista médica, se percibió una discrepancia en su conducta gestual durante la donación de sangre. Conclusión. Se evidenció una concordancia entre la exclusión interna y la serología reactiva (9%) y/o autoexclusión (7,2%). Este trabajo reafirma el valor de la entrevista predonación como primera barrera para la seguridad transfusional.

Introduction. The interview prior to the donation is a key factor during the donors' selection. The interviewer's skills are essential to go beyond the simple regulations knowledge. Other skills must be developed during the interview in order to gain empathy with the potential donor; trying to perceive if there is any dissociation between donor's gestures, words, looks, postures and voice tones (analog communication) and his verbal communication (digital communication). Method. A research was carried out about the reactive serology and the auto-exclusion of blood donors whose units were discarded by internal exclusion as -although they had passed the medical interview- a discrepancy in their nonverbal behaviours was perceived during the blood donation. Conclusion. A concordance was founded between the internal exclusion and the reactive serology (9%) and/or auto-exclusion (7,2%). This research reaffirms the importance of the interview prior to the donation as first barrier to ensure transfusion safety.

Analysis of IL-10, IL-4 and TNF-alpha polymorphisms in drug-induced liver injury (DILI) and its outcome.

BACKGROUND/AIMS: The aim of this study was to assess whether genetic polymorphism of three important candidate cytokine genes, IL-10 (-1082G/A, -819C/T, and -592C/A), IL-4 (-590C/T) and TNF-alpha (-308G/A), play a role in the susceptibility to developing drug-induced liver injury (DILI), and in determining its phenotypic expression and severity. METHODS: Cytokine genotyping was analysed using TaqMan 5' allelic discrimination assay in 140 DILI patients (mean age 51 y, range 13-82, with equal sex distribution) included in the Spanish Registry and 268 healthy controls. RESULTS: Genotypes, haplotypes and allele frequencies were similar for both cases and controls. The low IL-10 producing haplotype was more prevalent in DILI patients with the absence of peripheral blood eosinophilia (Pc=0.004, OR=5.29, 95% CI: 2.04-13.67), revealing significantly lower median eosinophil counts (0.19 x 10(9)L; P<0.0002) compared to the intermediate (0.24 x 10(9)L) and high (0.40 x 10(9)L) IL-10 haplotypes. All cases with serious DILI outcome carried low or intermediate IL-10 producing haplotype and had normal or low eosinophil counts. CONCLUSIONS: IL-10, IL-4 and TNF-alpha genetic polymorphisms were not related to the risk of developing DILI. Low IL-10 producing haplotype is associated with low eosinophil count, absence of eosinophilia and may be associated with worse clinical outcome from DILI.

Primera asistencia ventricular pediátrica prolongada (Berlin Heart) en la República Argentina / First Prolonged Pediatric Ventricular Assistance (Berlin Heart) in Argentina

Se implantó exitosamente un dispositivo de asistencia ventricular paracorpórea neumática -Berlin Heart-Excor- como soporte ventricular izquierdo prolongado en una niña de 8 kg de peso, con diagnóstico de origen anómalo de la arteria coronaria izquierda de la arteria pulmonar, miocardiopatía dilatada grave y trombosis intraauricular. Simultáneamente, se resecó un trombo de la aurícula izquierda y se reimplantó la coronaria anómala en la aorta ascendente. Luego de 27 días de soporte, la mejoría de la función ventricular izquierda permitió discontinuar la asistencia ventricular, con evolución satisfactoria. Dieciocho meses después, la niña desarrolla una vida normal.

A paracorporeal pneumatic ventricular assist device -Berlin Heart-Excor- was successfully implanted as a prolonged left ventricle support in a female infant (weight 8 kg), with a diagnosis of anomalous origin of left coronary artery from pulmonary artery, severe dilated myocardiopathy and intra-atrial thrombosis. At the same time, a thrombus from the left atrial appendage was resected, and the anomalous coronary artery was implanted in the ascending aorta. After 27 days of support, left ventricular function improved enough to wean from ventricular assistance, with favorable outcome. Eighteen months later, the girl carries on a normal living.

Surgical approach to left ventricular inflow obstruction due to dilated coronary sinus.

BACKGROUND: Left superior vena cava draining to a dilated coronary sinus can cause left ventricular inflow obstruction. Our purpose is to report 4 severely ill patients with this malformation who were operated upon and in whom repair was accomplished using an original surgical approach. METHODS: An operative procedure was designed, which included complete resection of the wall of the coronary sinus along its entire extension in the left atrium; division of the left superior vena cava; and establishment of the left superior vena cava-right atrial continuity by a wide left superior vena cava-right atrial appendage anastomosis. The series included 1 patient with interrupted inferior vena cava-hemiazygous continuation to left superior vena cava. RESULTS: There were no deaths. Absence of residual left ventricular inflow obstruction was demonstrated at follow-up in all cases, together with an unobstructed left superior vena cava-right atrial appendage-right atrial connection. CONCLUSIONS: A predictable relief of the left ventricular inflow obstruction, together with preservation of an adequate drainage for the systemic venous return, were both achieved with this repair.