Differential efficacy with epidural blood and fibrin patches for the treatment of post-dural puncture headache.

BACKGROUND: Accidental dural puncture (ADP) is the most frequent major complication when performing an epidural procedure in obstetrics. Consequently, loss of pressure in the cerebrospinal fluid (CSF) leads to the development of post-dural puncture headache (PDPH), which occurs in 16%-86% of cases. To date, the efficacy of epidural fibrin patches (EFP) has not been evaluated in a controlled clinical trial, nor in comparative studies with epidural blood patches (EBP). METHODS: The objective of the present study was to compare the efficacy of EFP with respect to EBP for the treatment of refractory accidental PDPH. This prospective, randomized, open-label, parallel, comparative study included 70 puerperal women who received an EBP or EFP (35 in each group) after failure of the conventional analgesic treatment for accidental PDPH in a hospital. RESULTS: A higher percentage of women with EFP than EBP achieved complete PDPH relief after 2 (97.1% vs. 54.3%) and 12 h (100.0% vs. 65.7%) of the patch injection. The percentage of patients who needed rescue analgesia was significantly lower with EFP after 2 (2.9% vs. 48.6%) and 12 h (0.0% vs. 37.1%). After 24 h, PDPH was resolved in all women who received EFP. The recurrence of PDPH was reported in one woman from the EBP group (2.9%), who subsequently required a second patch. The mean length of hospital stay was significantly lower with EFP (3.9 days) than EBP (5.9 days). Regarding satisfaction, the mean value (Likert scale) was significantly higher with EFP (4.7 vs. 3.0). CONCLUSIONS: EFP provided better outcomes than EBP for the treatment of obstetric PDPH in terms of efficacy, safety, and patient satisfaction.

PD-1 genotype of the donor is associated with acute graft-versus-host disease after HLA-identical sibling donor stem cell transplantation.

Programmed death 1 (PD-1) activation triggers an immune checkpoint resulting in inhibition of T cells that leads to peripheral tolerance. Some PD-1 polymorphisms have been described and associated with the development of autoimmune diseases or cancer predisposition, but there are few data concerning the relevance of such polymorphisms on the clinical outcome after allogeneic hematopoietic stem cell transplant (alloHSCT). We analyzed the distribution of the SNPs PD-1.1G/A (rs36084323) and PD-1.3G/A (rs11568821) genotypes of the donor in a cohort of 1485 alloHSCT from HLA-identical sibling donors. We found an increased risk of grades II to IV graft-versus-host disease (GvHD) in patients receiving grafts from donors homozygous for the G allele at the rs36084323 SNP (P = 0.033; hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.1 to 4.8) and also from donors homozygous for the A allele at the rs11568821 position (P < 0.001; HR 4.5, 95%CI 2.0 to 10.1). In contrast, the PD-1 genotype of the donor did not show association with overall survival or relapse incidence. These results suggest that the PD-1 genotype of the donor plays an important role for the development of acute GvHD after alloHSCT from HLA-identical sibling donors.

Donor CTLA-4 Genotype Modulates the Immune Response to Minor Histocompatibility Antigen Mismatches.

Minor histocompatibility antigen (miHA) mismatches have been related to graft-versus-host disease (GVHD) after allogeneic stem cell transplantation, but this association remains controversial due to the lack of consistency in the results obtained by different groups. The CTLA-4 genotype of the donor has been reported to be relevant in the appearance of acute GVHD. We explored the effect of the donor's CTLA-4 genotype in the incidence of acute GVHD associated with HA-1, HA-8, or H-Y miHA mismatches in a large cohort of 1295 patients receiving an allogeneic transplant from an HLA-identical sibling donor. The incidence of acute GVHD was higher if the donor and recipient were mismatched for HA-1, HA-8, or H-Y, but only when the donor had the CTLA-4 rs231775 AA genotype (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.27 to 3.75; P = .005; HR, 2.11, 95% CI, 1.06 to 4.18; P = .033; and HR, 1.50; 95% CI, 1.05 to 2.15; P = .025, respectively). In contrast, this increased risk of developing acute GVHD was not found when the donor presented the CTLA-4 rs231775 AG or GG genotypes. We conclude that the immune response to specific miHA mismatches is modulated by the CTLA-4 genotype of the donor.

Rabbit antithymocyte globulin versus horse antithymocyte globulin for treatment of acquired aplastic anemia: a retrospective analysis.

Studies comparing rabbit antithymocyte globulin (rATG) and horse ATG (hATG) in patients with aplastic anemia (AA) have shown conflicting results. These studies included fewer than 60 subjects in the rATG arm with relatively short follow-up. A total of 169 patients treated with rATG and 62 treated with hATG were included in this retrospective analysis, across 33 centers. Patients were treated with rATG or hATG plus cyclosporine A. Over half were classified, as having severe AA (SAA) or very severe AA (VSAA), and the mean follow-up was 45 months. There was no significant difference detected in cumulative response to treatment or survival between the rATG and hATG groups. The response to treatment was 63 % in the rATG group versus 66 % in the hATG group at 3 months. By 12 months, this pattern had reversed, and 84 % of rATG patients had responded to treatment versus 76 % in the hATG group (n.s.). Early mortality due to infection tended to be higher with rATG compared to hATG (n.s). rATG and hATG would seem to be therapeutically equivalent in SAA and VSAA. However, patients treated with rATG may take longer to respond than those treated with hATG and may also require more active prevention of early infections.

Findings and Challenges in Replacing Traditional Uterine Cervical Cancer Diagnosis with Molecular Tools in Private Gynecological Practice in Mexico.

We have been encouraging practicing gynecologists to adopt molecular diagnostics tests, PCR, and cancer biomarkers, as alternatives enabled by these platforms, to traditional Papanicolaou and colposcopy tests, respectively. An aliquot of liquid-based cytology was used for the molecular test [high-risk HPV types, (HR HPV)], another for the PAP test, and one more for p16/Ki67 dual-stain cytology. A total of 4499 laboratory samples were evaluated, and we found that 25.1% of low-grade samples and 47.9% of high-grade samples after PAP testing had a negative HR HPV-PCR result. In those cases, reported as Pap-negative, 22.1% had a positive HR HPV-PCR result. Dual staining with p16/Ki67 biomarkers in samples was positive for HR HPV, and 31.7% were also positive for these markers. Out of the PCR results that were positive for any of these HR HPV subtypes, n 68.3%, we did not find evidence for the presence of cancerous cells, highlighting the importance of performing dual staining with p16/Ki67 after PCR to avoid unnecessary colposcopies. The encountered challenges are a deep-rooted social reluctance in Mexico to abandon traditional Pap smears and the opinion of many specialists. Therefore, we still believe that colposcopy continues to be a preferred procedure over the dual-staining protocol.

Polymer Conjugation of Docosahexaenoic Acid Potentiates Cardioprotective Therapy in Preclinical Models of Myocardial Ischemia/Reperfusion Injury.

While coronary angioplasty represents an effective treatment option following acute myocardial infarction, the reperfusion of the occluded coronary artery can prompt ischemia-reperfusion (I/R) injury that significantly impacts patient outcomes. As ω-3 polyunsaturated fatty acids (PUFAs) have proven, yet limited cardioprotective abilities, an optimized polymer-conjugation approach is reported that improves PUFAs bioavailability to enhance cardioprotection and recovery in animal models of I/R-induced injury. Poly-l-glutamic acid (PGA) conjugation improves the solubility and stability of di-docosahexaenoic acid (diDHA) under physiological conditions and protects rat neonatal ventricular myocytes from I/R injury by reducing apoptosis, attenuating autophagy, inhibiting reactive oxygen species generation, and restoring mitochondrial membrane potential. Enhanced protective abilities are associated with optimized diDHA loading and evidence is provided for the inherent cardioprotective potential of PGA itself. Pretreatment with PGA-diDHA before reperfusion in a small animal I/R model provides for cardioprotection and limits area at risk (AAR). Furthermore, the preliminary findings suggest that PGA-diDHA administration in a swine I/R model may provide cardioprotection, limit edema and decrease AAR. Overall, the evaluation of PGA-diDHA in relevant preclinical models provides evidence for the potential of polymer-conjugated PUFAs in the mitigation of I/R injury associated with coronary angioplasty.

Transcatheter Mitral Repair for Functional Mitral Regurgitation According to Left Ventricular Function: A Real-Life Propensity-Score Matched Study.

BACKGROUND: Transcatheter mitral valve repair (TMVR) could improve survival in functional mitral regurgitation (FMR), but it is necessary to consider the influence of left ventricular ejection fraction (LVEF). Therefore, we compare the outcomes after TMVR with Mitraclip® between two groups according to LVEF. METHODS: In an observational registry study, we compared the outcomes in patients with FMR who underwent TMVR with and without LVEF <30%. The primary endpoint was the combined one-year all-cause mortality and unplanned hospital readmissions due to HF. The secondary end-points were New York Heart Association (NYHA) functional class and mitral regurgitation (MR) severity. Propensity-score matching was used to create two groups with the same baseline characteristics, except for baseline LVEF. RESULTS: Among 535 FMR eligible patients, 144 patients with LVEF <30% (group 1) and 144 with LVEF >30% (group 2) had similar propensity scores and were included in the analyses. The primary study endpoint was significantlly higher in group 1 (33.3% vs. 9.4%, p = 0.002). There was a maintained improvement in secondary endpoints without significant differences among groups. CONCLUSION: FMR patients with LVEF <30% treated with MitraClip® had higher mortality and readmissions than patients with LVEF ≥30% treated with the same device. However, both groups improved the NYHA functional class and MR severity.

[Invasive strategy in patients with advanced diabetes and non-ST-segment elevation acute coronary syndrome. Angiographic findings and clinical follow-up. PREDICAR study results]. / Estrategia invasiva en pacientes con diabetes avanzada y síndrome coronario agudo sin elevación del segmento ST. Hallazgos angiográficos y evolución clínica. Resultados del estudio PREDICAR.

INTRODUCTION AND OBJECTIVES: Advanced diabetes can be associated with diffuse coronary artery disease that is difficult to treat by revascularization. We studied angiographic findings and disease progression in patients with advanced diabetes (either insulin-dependent or taking antidiabetic drugs for >5 years) and non-ST-elevation acute coronary syndrome who were being treated using an invasive strategy. METHODS: The study included 141 patients. The extent of the coronary artery disease was quantified using a score derived from a 29-segment coronary angiogram. The composite endpoint was death, myocardial infarction, or readmission for unstable angina within one year of follow-up. RESULTS: The extent of coronary disease was associated with Killip class >1 at admission (P=.02), previous coronary surgery (P=.003), ST-segment depression (P=.01), and a poor ejection fraction (P=.0001). The more of these factors present (i.e., 0, 1, 2 or 3 factors), the greater the extent of the coronary disease (i.e., 12 [7], 15 [7], 21 [6] and 23 [7] points, respectively; P=.0001). There was a significant difference between patients with > or =2 factors and those with P=.02), even after adjustment using a revascularization propensity score (C-index 0.80). CONCLUSIONS: In patients with non-ST-elevation acute coronary syndrome and advanced diabetes being managed using an invasive strategy, a history of coronary surgery, ST-segment depression and poor left ventricular function were all associated with the presence of diffuse coronary artery disease. Clinical follow-up indicated that revascularization during hospital admission improved prognosis.

Role of Oxidative Stress and Mitochondrial Dysfunction in Skeletal Muscle in Type 2 Diabetic Patients.

Type 2 diabetes can increase the risk of skeletal muscle dysfunction and, consequently, that of cardiovascular diseases, including coronary artery disease and stroke. It is also related to a reduced capacity for exercise, but the underlying mechanism is only partially understood. There are several factors that contribute to the development of skeletal muscle dysfunction, of which oxidative stress and mitochondrial dysfunction are among the most important. This review discusses the role of oxidative stress in the development and progression of skeletal and cardiac dysfunction associated with diabetes. It also provides an overview of the potential actions of antioxidants in general and mitochondria-targeted antioxidants in particular in the treatment of muscle dysfunction in type 2 diabetes.

Model generation of coronary artery bifurcations from CTA and single plane angiography.

PURPOSE: To generate accurate and realistic models of coronary artery bifurcations before and after percutaneous coronary intervention (PCI), using information from two image modalities. Because bifurcations are regions where atherosclerotic plaque appears frequently and intervention is more challenging, generation of such realistic models could be of high value to predict the risk of restenosis or thrombosis after stent implantation, and to study geometrical and hemodynamical changes. METHODS: Two image modalities have been employed to generate the bifurcation models: computer tomography angiography (CTA) to obtain the 3D trajectory of vessels, and 2D conventional coronary angiography (CCA) to obtain radius information of the vessel lumen, due to its better contrast and image resolution. In addition, CCA can be acquired right before and after the intervention in the operation room; therefore, the combination of CTA and CCA allows the generation of realistic preprocedure and postprocedure models of coronary bifurcations. The method proposed is semiautomatic, based on landmarks manually placed on both image modalities. RESULTS: A comparative study of the models obtained with the proposed method with models manually obtained using only CTA, shows more reliable results when both modalities are used together. The authors show that using preprocedure CTA and postprocedure CCA, realistic postprocedure models can be obtained. Analysis carried out of the Murray's law in all patient bifurcations shows the geometric improvement of PCI in our models, better than using manual models from CTA alone. An experiment using a cardiac phantom also shows the feasibility of the proposed method. CONCLUSIONS: The authors have shown that fusion of CTA and CCA is feasible for realistic generation of coronary bifurcation models before and after PCI. The method proposed is efficient, and relies on minimal user interaction, and therefore is of high value to study geometric and hemodynamic changes of treated patients.

[Predictive value of differential pulse pressure in the diagnosis of silent myocardial ischemia in patients with type-2 diabetes]. / Valor predictivo de la presión diferencial del pulso en el diagnóstico de isquemia miocárdica silente en pacientes con diabetes tipo 2.

Silent myocardial ischemia occurs more frequently in diabetics. Differential arterial pulse pressure is a valuable predictor of cardiovascular disease. We studied 48 consecutive male patients with type-2 diabetes and no known history of ischemic heart disease. Ambulatory monitoring of arterial pressure was carried out and the presence of silent myocardial ischemia was studied using a protocol that involved: resting ECG, echocardiography, 24-hour Holter ECG, conventional exercise stress testing, and exercise testing with nuclear scanning. Nine patients (19%) had silent myocardial ischemia. Differential pulse pressure had good discriminative ability in identifying the presence of silent ischemia: the area under the receiver operating characteristic (ROC) curve was 0.83 (95% confidence interval [CI], 0.71-0.96; P=.002). This predictive ability was also observed on adjusted logistic regression modeling (odds ratio [OR], 1.24, 95% CI = 1.02-1.49). We found that the OR for the risk of silent ischemia for every 10-mmHg increase in differential pulse pressure was 8.5 (95% CI 1.7-31.2). Age and differential pulse pressure were the only independent predictors of silent myocardial ischemia found in this study.

Sirolimus as part of immunosuppressive therapy for refractory chronic graft-versus-host disease.

Many patients receiving allogeneic stem cells develop chronic graft-versus-host disease (cGVHD), which remains as the main cause of morbidity and mortality. Although the first line of therapy is generally with steroids, it is not well known how to manage refractory cases. Those patients are usually treated with alternative experimental agents. Sirolimus (Rapamycin), a new immunosuppressive agent, inhibits signal transduction and cell cycle progression after binding to FKBP12. We report a retrospective analysis with sirolimus in transplant recipients with cGVHD refractory to previous immunosuppressive therapy. Forty-seven patients with refractory or relapsed cGVHD were treated with the combination of sirolimus and calcineurin inhibitors (n = 33), mycophenolate (n = 9), or prednisone (n = 5). Thirty-eight of 47 (81%) patients had clinical responses (complete = 18, partial = 20). The main toxicity was mild renal failure, particularly at the start of therapy. Four patients who presented thrombotic microangiopathy were managed with plasmapheresis and the discontinuation of sirolimus and calcineurin inhibitors. Statistical analysis showed the type of cGVHD onset and presirolimus clinical status as the main variables influencing the response to treatment. The Kaplan-Meier estimate of survival was 57.4% at 3 years. The current study shows the efficacy and safety of sirolimus in refractory cGVHD patients. Further investigation is warranted to elucidate the role of sirolimus in cGVHD, and find the best combination (sirolimus + calcineurin inhibitors versus others) for therapeutic use.

Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol.

We report the results of reduced-intensity conditioning allogeneic stem cell transplantation (allo-RIC) in patients with advanced Hodgkin lymphoma (HL). Forty patients with relapsed or refractory HL were homogeneously treated with an RIC protocol (fludarabine 150 mg/m(2) intravenously plus melphalan 140 mg/m(2) intravenously) and cyclosporin A and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Twenty-one patients (53%) had received >2 lines of chemotherapy, 23 patients (58%) had received radiotherapy, and 29 patients (73%) had experienced treatment failure with a previous autologous stem cell transplantation. Twenty patients (50%) were allografted in resistant relapse, and 38 patients received hematopoietic cells from an HLA-identical sibling. Five patients (12%) died from early transplant-related mortality (before day +100 after allo-RIC). One-year transplant-related mortality was 25%. Acute GVHD developed in 18 patients (45%). Chronic GVHD developed in 17 (45%) of the 31 evaluable patients. The response rate 3 months after the allo-RIC was 67% (21 [52%] complete remissions and 6 [15%] partial remissions). Eleven patients received donor lymphocyte infusions (DLIs) for disease relapse. The response rate after DLI was 54% (3 complete remissions and 3 partial remissions). Overall survival (OS) and progression-free survival (PFS) were 48% +/- 10% and 32% +/- 10% at 2 years, respectively. Refractoriness to chemotherapy was the only adverse prognostic factor for both OS (63% +/- 12% versus 35% +/- 13%; P = .05) and PFS (55% +/- 16% versus 10% +/- 9%; P = .006). For patients with failure of a prior autologous hematopoietic stem cell transplantation, results were especially good for those who experienced late relapses (>/=12 months: 2-year OS and PFS were 75% +/- 16% and 70% +/- 18%, respectively). These data suggest that allo-RIC is feasible in heavily pretreated HL patients and has an acceptable early transplant-related mortality. Results are better in patients allografted in sensitive disease. Both responses observed after the development of GVHD and DLI may suggest a graft-versus-HL effect. Allo-RIC has to be considered an effective therapeutic approach for patients who have had treatment failure with a previous autologous hematopoietic stem cell transplantation.

Nuestra experiencia en las fracturas de tobillo en los adultos

Presentamos nuestra experiencia en el tratamiento de fracturas de tobillo en adultos, desarrollada entre los meses de enero de 1987 a marzo de 1991. Utilizamos para este trabajo la clasificación de Lauge-Hansen, clasificación genética o etiopatogénica. Fueron evaluados 263 pacientes, de los cuales el 57 por ciento perteneció al sexo masculino y 43 por ciento al femenino. Respecto del mecanismo lesional, el más frecuente fue el de traumatismo por rotación externa sin diastasis de la TPI (supinación-rotación externa -SER) (52,2 por ciento) seguido de traumatismo por rotación externa con diastasis de la TPI (pronación-rotación externa -PER-) (21,5 por ciento), aducción (14,7 por ciento), abducción (6,8 por ciento) e inclasificables (4,7 por ciento). Respecto de la cirugía, realizamos una incisión anterolateral, la que nos permite revisar sistemáticamente la sindesmosis tibioperonea y repararla en caso necesario, utilizando en ciertos casos una placa de neutralización modificada. Con la utilización de mecha flexible y destornillador articulado se facilita la osteosíntesis del maléolo tibial sin dificultades técnicas, disminuyendo la posibilidad de lesión de partes blandas y el tiempo quirúrgico. Siempre reparamos las lesiones ligamentarias asociadas. Consideramos a los fijadores externos como una opción valedera y muy importante en casos de fracturas expuestas con grave atrición de tejidos, dado que su fijación reduce el microtraumatismo agregado sobre los tejidos ocasionado por el foco fracturario y permite curaciones periódicas sin dificultad. También los utilizamos ante fracturas conminutas de pilón tibial, por el principio de la ligamentopexia

Resolución de las fracturas de radio distal según su complejidad

Entre enero de 1991 y enero de 1993 asistimos un total de 396 fracturas de radio distal en pacientes adultos. Es nuestro objetivo el análisis de los resultados obtenidos, siguiendo un protocolo que luego de evaluar el tipo de fractura y las características del paciente oriente hacia distintas alternativas terapéuticas que van desde la inmovilización enyesada hasta la osteosíntesis y la aplicación del concepto de la ligamentotaxia mediante el uso de fijadores externos. Destacamos la importancia de realizar un diagnóstico preciso del tipo de lesión, así como también la realización de evaluaciones funcionales y anatómicas rigurosas, a fin de obtener nuevas claves para la resolución de esta compleja lesión