An in vitro comparison of intra-operative isohemagglutinin and human leukocyte antigen removal techniques in pediatric heart transplantation.

BACKGROUND: Highly sensitized pediatric patients awaiting heart transplantation experience longer wait times and thus higher waitlist mortality. Similarly, children less than 2 years of age have increased waitlist times and mortality when compared to their older peers. To improve the likelihood of successful transplantation in these patients, various strategies have been utilized, including peri-operative plasmapheresis. However, limited data exists comparing plasmapheresis techniques for antibody reduction. This study's aim was to compare the in vitro magnitude of isohemagglutinin titers (IT) and human leukocyte antigen (HLA) antibody removal and the time required between membrane-based plasmapheresis (MP) and centrifuge-based plasmapheresis (CP) incorporated into the extracorporeal (EC) circuit. METHODS: Two MP (Prismaflex) and two CP (Spectra Optia, Terumo BCT) circuits were incorporated into four separate EC circuits primed with high titer, highly sensitized type O donor whole blood. Assays were performed to determine baseline IT and anti-HLA antibodies and then at 30-minute increments until completion of the run (two plasma volume exchanges) at two hours. RESULTS: There was a decrease in anti-A and anti-B IgM and IgG titers with both MP and CP. Mean anti-A and anti-B titer reduction was by 4.625 titers (93.7% change) and 4.375 titers (93.8% change) using MP and CP, respectively. At 2 h of apheresis, CP reduced 62.5% of all ITs to ≤ 1:4, while MP reduced 50% of ITs to ≤ 1:4. Additionally, reduction of anti-HLA class II antibody to mean fluorescence intensity (MFI) <3000 was achieved with both MP and CP. At 2 h of apheresis, CP reduced MFI by 2-3.5 fold and MP reduced MFI by 1.7-2.5 fold. Both demonstrated similar hemolytic and thrombotic profiles. CONCLUSIONS: In this in vitro plasmapheresis model of IT and anti-HLA antibody reduction, both MP and CP incorporated into the EC circuit can be used quickly and effectively to reduce circulating antibodies. While CP may have some greater efficiency, further study is necessary to verify this in vivo.

Carfilzomib in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma: A Phase I Trial.

INTRODUCTION: We designed a multicenter, phase Ib dose-escalation trial of carfilzomib with bendamustine and rituximab in patients with relapsed/refractory non-Hodgkin lymphoma (NCT02187133) in order to improve the response rates of this difficult-to-treat population. Chemoimmunotherapy with bendamustine and rituximab has shown activity in a variety of lymphomas, and proteasome inhibitors have demonstrated pre-clinical synergy and early clinical activity in this population. The objectives were to determine the maximum tolerated dose of carfilzomib and the preliminary efficacy of this combination. PATIENTS AND METHODS: The protocol followed a 3+3 design of carfilzomib dose escalation combined with standard doses of bendamustine and rituximab. Patients were treated for up to 6 cycles with an interim positron emission tomography/computed tomography after cycle 3. RESULTS: Ten patients were treated on the dose-escalation phase. The study was terminated at a carfilzomib dose of 56 mg/m2, and the maximum tolerated dose was not reached. The most common grade 3/4 adverse event was thrombocytopenia. There was 1 dose-limiting toxicity observed, grade 3 febrile neutropenia, and there were no treatment-related deaths. The overall response rate was 40% (complete response rate, 30%), with a median duration of response of 12 months and a median progression-free survival of 2.1 months. CONCLUSION: Carfilzomib in combination with bendamustine and rituximab is a safe and well-tolerated treatment for patients with relapsed/refractory non-Hodgkin lymphoma. Preliminary data indicate that this combination may have efficacy with an acceptable side effect profile in this heavily pre-treated patient population with limited treatment options.

Infecciones del sitio quirúrgico post craneotomías y sus factores de riesgo relacionados / Infections of the post-craniotomy surgical site and its related risk factors

Introducción: A pesar de los avances científicos, la infección post cirugía sigue siendo importante causa de morbilidad y mortalidad. Objetivos: Determinar tasa de incidencia, analizar factores de riesgo y caracterizar las infecciones del sitio quirúrgico (ISQ). Pacientes y métodos: Estudio cuantitativo, descriptivo, correlacional, retrospectivo de corte transversal, de 117 expedientes de pacientes con craneotomías limpias, que reunieron los criterios de inclusión del servicio de neurocirugía de adulto del Hospital Mario Catarino Rivas de junio del 2016 a mayo del 2017. Resultados: La tasa de incidencia de ISQ fue del 11,97%, que ocupó el primer lugar en incidencia junto con las infecciones de origen pulmonar. Las ISQ en heridas limpias fueron 10% y 30% en heridas con cuerpo extraño. Los agentes etiológicos más frecuentes fueron los bacilos gramnegativos. Los principales factores de riesgo intrínsecos fueron el sexo femenino ([OR] Odds Ratio=3), clasificación ASA I (OR=4.4) y la patología tumoral (OR=3.3); los extrínsecos fueron, hospitalización de más de 30 días (OR=5.4), re-intervenciones (OR=3.8), fuga de Liquido Cefalorraquideo (LCR) (OR=136), transfusión sanguínea (OR=12.6), catéter venoso central (OR=5.3), catéter vesical más de 72 horas (OR=6.7), traqueotomía (OR=4.2), injerto dural (OR=6.5) y sin drenaje postquirúrgico (OR=4.6). Conclusión: La incidencia de ISQ fue alta, con mayor proporción en mujeres y en edad de 31 a 40 años. Tres factores de riesgo intrínsecos y nueve extrínsecos se relacionaron significativamente con ISQ, revelando mayor número de factores modificables.

An investigation of stigma in individuals receiving treatment for substance abuse.

This study examined the impact of stigma on patients in substance abuse treatment. Patients (N=197) from fifteen residential and outpatient substance abuse treatment facilities completed a survey focused on their experiences with stigma as well as other measures of drug use and functioning. Participants reported experiencing fairly high levels of enacted, perceived, and self-stigma. Data supported the idea that the current treatment system may actually stigmatize people in recovery in that people with more prior episodes of treatment reported a greater frequency of stigma-related rejection, even after controlling for current functioning and demographic variables. Intravenous drug users, compared to non-IV users, reported more perceived stigma as well as more often using secrecy as a method of coping. Those who were involved with the legal system reported less stigma than those without legal troubles. Higher levels of secrecy coping were associated with a number of indicators of poor functioning as well as recent employment problems. Finally, the patterns of findings supported the idea that perceived stigma, enacted stigma, and self-stigma are conceptually distinct dimensions.

Augmenting continuing education with psychologically focused group consultation: Effects on adoption of group drug counseling.

This study examines whether adding psychologically focused group consultation to a standard 1-day continuing-education workshop on Group Drug Counseling (GDC), a group therapy with evidence of effectiveness in the treatment of substance abuse problems, improves GDC adoption. Counselors who had taken a 1-day workshop were randomly assigned to an 8-week course of group consultation that met for 1.5 hr per session (n = 16) or to no additional contact (n = 14). The group consultation used Relapse Prevention and Acceptance and Commitment Therapy principles to help participants overcome psychological barriers to the adoption of GDC. Results showed that the 1-day workshop resulted in attempts by trainees to implement the new therapy, but that the consultation condition maintained significantly higher levels of adoption and 2- and 4-month followups. Additionally, those in the group consultation condition reported a higher sense of personal accomplishment at the 4-month followup. These findings suggest that empirically supported psychotherapy models can be used to decrease clinicians' psychological barriers to adoption of evidence-based psychotherapy methods. (PsycINFO Database Record (c) 2010 APA, all rights reserved).