Total elbow arthroplasty in haemophilia.

INTRODUCTION: Advanced haemophilic arthropathy of the elbow can be a devastating manifestation of severe haemophilia with significant implications for activities of daily living. AIM: To summarize the currently available data on total elbow arthroplasty (TEA) for haemophilic arthropathy of the elbow, to draw comparisons to TEA for other indications, and to outline some considerations regarding TEA in this unique population. METHODS: A narrative review of the literature has been performed. RESULTS: The scant data regarding outcomes of TEA for haemophilic arthropathy are limited to small case series and case reports. A review of the available literature shows that, while pain relief and patient satisfaction are promising, variable outcomes with significant complications and infection rates may discourage routine use of TEA for haemophilic arthropathy of the elbow. CONCLUSION: While patients with severe haemophilic arthropathy of the elbow are likely to make gains in terms of pain control and range of motion following TEA, there are insufficient data to routinely recommend its use. Complication and infection rates are concerning, and the lack of survival analysis data makes it difficult to quantify the benefit to the patient in light of the risks and resources involved in the procedure.

Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia.

VM202, a plasmid DNA that expresses two isoforms of hepatocyte growth factor, may elicit angiogenic effects that could benefit patients with critical limb ischemia (CLI). In a phase 2, double-blind trial in 52 CLI patients, we examined the safety and potential efficacy of intramuscular injections of low-dose (n=21) or high-dose (n=20) VM202 or placebo (n=11) in the affected limb (days 0, 14, 28 and 42). Adverse events and serious adverse events were similar among the groups; no malignancy or proliferative retinopathy was seen. In exploratory efficacy analyses, we found no differences in ankle or toe-brachial index, VAS, VascuQuol or amputation rate among the groups. Complete ulcer healing was significantly better in high-dose (8/13 ulcers; P<0.01) versus placebo (1/9) patients. Clinically meaningful reductions (>50%) in ulcer area occurred in high-dose (9/13 ulcers) and low-dose (19/27) groups versus placebo (1/9; P<0.05 and P<0.005, respectively). At 12 months, significant differences were seen in TcPO2 between the high-dose and placebo groups (47.5 ± 17.8 versus 36.6 ± 24.0 mm Hg, respectively; P<0.05) and in the change from baseline among the groups (P<0.05). These data suggest that VM202 is safe and may provide therapeutic bioactivity in CLI patients.

Association between TNF-α-308G>A and -238G>A gene polymorphisms and TNF-α serum levels in Mexican colorectal cancer patients.

The objective of this study was to examine the association between TNF-α serum levels and -308G>A and -238G>A polymorphisms in the corresponding gene by comparing healthy subjects to colorectal cancer (CRC) patients from a Mexican population. Serum levels of TNF-α were found to significantly differ between CRC patients and controls (P = 0.001), but no relationship between the -308G>A and -238G>A polymorphisms and increased CRC risk was established (P > 0.05). However, an association between the -308G>A variant and disease became evident when the distribution of AA-GA genotypes was examined in patients with hematologic toxicity (neutropenia) and those without (odds ratio = 3.356, 95% confidence interval = 1.295- 8.698, P = 0.013). The GG haplotype was more common in controls than CRC patients, with a frequency of 0.85 among the former, but this difference was not significant (P > 0.05). In conclusion, TNF-α serum levels and AA-AG genotypes of the TNF-α-308G>A polymorphism may significantly contribute to CRC susceptibility in the population examined in this investigation.

Fertilization capacity of cryopreserved Iberian ibex epididymal sperm in a heterologous in vitro fertilization assay.

In vitro fertilization (IVF) can be used to assess the fertilization capacity of sperm. Heterologous IVF may be useful when assessing that of wild animals as it is often difficult to obtain adequate numbers of naturally corresponding oocytes. The aim of the present study was to assess the fertilization capacity of frozen-thawed ibex epididymal spermatozoa via heterologous IVF involving the oocytes of prepubertal domestic goats. The effect on fertilization and embryo development of adding oestrous sheep serum (ESS) to the fertilization medium was also examined. Cumulus-oocyte complexes (COCs) were matured in TCM-199 for 24-27 h at 38.5°C in a 5% CO2 in air atmosphere. Frozen-thawed epididymal spermatozoa were selected by density gradient centrifugation. After maturation, the oocytes were co-incubated with spermatozoa in synthetic oviductal fluid (SOF) with different concentrations of ESS: SOF-C (0%), SOF-2 (2%) and SOF-20 (20%). At 17 h post-insemination (hpi), zygotes with one female and one male pronucleus (2PN) were categorised as normal; zygotes with 3PN were recorded as polyspermic, and oocytes with 1PN as asynchronous. Cleavage and blastocyst development were assessed at 48 and 168 hpi respectively. The percentage of zygotes with 2PN was higher in the SOF-2 than in the SOF-20 treatment group (27.7% versus 2.9% P < 0.05). The percentage of blastocysts formed with the SOF-C, SOF-2 and SOF-20 treatments were 1.1%, 7.5% and 0% respectively. These results show that the presence of 2% ESS achieves better results than the use of no serum or the standard 20% concentration. Heterologous IVF may be an effective method for predicting the fertilization capacity of ibex spermatozoa, and therefore perhaps that of other wild mountain ungulates.

Sperm characteristics and heterologous in vitro fertilisation capacity of Iberian ibex (Capra pyrenaica) epididymal sperm, frozen in the presence of the enzymatic antioxidant catalase.

The aim of this work was to evaluate the protective effect of catalase (CAT) on frozen/thawed ibex epididymal sperm recovered post mortem, and to detect any harmful effect this might have on sperm fertilisation capacity. Epididymal spermatozoa were diluted using a Tris-citric acid-glucose medium (TCG) composed of 3.8% Tris (w/v), 2.2% citric acid (w/v), 0.6% glucose (w/v), 5% glycerol (v/v), and 6% egg yolk (v/v). Sperm masses from the right epididymis were diluted with TCG medium, while those from the left were diluted with TCG medium supplemented with 200IU/mL CAT. Heterologous in vitro fertilisation (IVF) was used to assess the fertilisation capacity of this sperm. The addition of CAT to the extender did not improve frozen/thawed sperm variables. Moreover, a reduced fertilisation capacity was detected: sperm diluted with TCG provided 25.5% 2PN zygotes, while just 13.2% was recorded for that diluted with TCG-CAT (P<0.01). The percentage of cleaved embryos at 48hpi was higher (P<0.01) with the TCG sperm than with the TCG-CAT sperm (16.7% vs. 7.6%). The use of 200IU/mL CAT as an additive cannot, therefore, be recommended for the preservation of ibex epididymal sperm. Other antioxidants should, however, be tested in both this and related wild mountain ungulates.

Variants rs2758346, rs5746094, and rs2758331 of SOD2 gene: association study with breast cancer in a Mexican population and their analysis in silico.

OBJECTIVE: The aim of the study was to analyze the association between the superoxide dismutase 2 (SOD2) gene variants rs2758346, rs5746094, and rs2758331 and breast cancer (BC) in the Mexican population as well as to perform in silico assessments of the variants' potential impact. PATIENTS AND METHODS: We performed in silico analysis and analyzed 489 healthy women and 467 BC patients using TaqMan assays and Real-Time PCR. RESULTS: The TT genotype, the T allele of the rs2758346 variant, and the CC genotype of both rs5746094 and rs2758331 were identified as BC risk factors (p < 0.05). The TT and CTTT genotype of the rs2758346 variant stratified by the presence of ki-67 (> 20%), TCCC, and estrogen receptor (ER)-positive of the rs5746094 variant, and the CC and CT genotypes of rs2758331 stratified by menopause status and non-chemotherapy response were risk factors. The TTC and TTA haplotypes are risk factors for BC. In silico analysis revealed that the rs2758346, rs5746094, and rs2758331 variants could influence SOD2 gene regulation by transcription factors and circulating RNAs (circRNAs). CONCLUSIONS: The rs2758346, rs5746094, and rs2758331 variants of the SOD2 gene were associated with BC risk and could influence SOD2 regulation by transcription factors and circRNAs.

Association of SOD1 gene variants (50 bp Ins/Del, rs4817415, rs2070424, rs1041740, rs17880135) with plasma protein levels in vitiligo patients and their analysis in silico.

OBJECTIVE: Vitiligo is a common systemic, idiopathic autoimmune disease. The aim of this study was to analyze the frequency of variants of the superoxide dismutase 1 (SOD1) gene (50 bp Ins/Del, rs4817415, rs2070424, rs1041740, rs17880135) and circulating plasma protein levels through in-silico analysis. PATIENTS AND METHODS: Blood samples were collected from adult patients of both sexes with a clinical diagnosis of vitiligo. ELISA tests for SOD and analysis of gene variants by qPCR were compared to a disease-free reference group. RESULTS: The population analyzed was young people between 29 and 37 years old, with a higher percentage of women. The population was found in the Hardy-Weinberg equilibrium (HWE). The 50 bp Ins/Del, rs4817415, and rs2070424 variants showed no significant difference between groups (p > 0.05). Although, in the dominant model, the CT and CTTT genotypes of the rs1041740 and rs17880135 variants showed an association with susceptibility to vitiligo compared to the control. Plasma SOD levels showed significant differences between the groups, and when stratified according to the genotypes of each variant, there was a significant difference, except with the rs17880135 variant. The haplotypes InsCGTC and InsAGCC are shown to be risk factors for susceptibility to vitiligo. The in-silico analysis demonstrated that the rs4817415, rs2070424, rs1041740, and rs17880135 variants of the SOD1 gene participate in the modification of selected regulatory elements for differentiating the protein, transcription factors, and long non-coding RNA. CONCLUSIONS: Information regarding the pathogenesis of vitiligo helps recognize risk factors and identify the relationship of diagnostic markers of cell damage inherent to the disease. This will help improve aspects of prevention and the choice of treatment alternatives appropriate to each case.

Association of the tumor necrosis factor-alpha -308G>A polymorphism with breast cancer in Mexican women.

The tumor necrosis factor-alpha (TNF-α) gene plays an important role in cell proliferation, differentiation, apoptosis, lipid metabolism, coagulation, insulin resistance, and endothelial function. Polymorphisms of TNF-α have been associated with cancer. We examined the role of the -308G>A polymorphism in this gene by comparing the genotypes of 294 healthy Mexican women with those of 465 Mexican women with breast cancer. The observed genotype frequencies for controls and breast cancer patients were 1 and 14% for AA, 13 and 21% for GA, and 86 and 65% for GG, respectively. We found that the odds ratio (OR) for AA genotype was 2.4, with a 95% confidence interval (95%CI) of 5.9-101.1 (P = 0.0001). The association was also evident when comparing the distribution of the AA-GA genotype in patients in the following categories: 1) premenopause and obesity I (OR = 3.5, 95%CI = 1.3-9.3, P = 0.008), 2) Her-2 neu and tumor stage I-II (OR = 2.5, 95%CI = 1.31-4.8, P = 0.004), 3) premenopause and tumor stage III-IV (OR = 1.7, 95%CI = 1.0-2.9, P = 0.034), 4) chemotherapy non-response and abnormal hematocrit (OR = 2.4, 95%CI = 1.2-4.8, P = 0.015), 5) body mass index and Her-2 neu and III-IV tumor stage (OR = 2.8, 95%CI = 1.2- 6.6, P = 0.016), and 6) nodule metastasis and K-I67 (OR = 4.0, 95%CI = 1.01-15.7, P = 0.038). We concluded that the genotypes AA-GA of the -308G>A polymorphism in TNF-α significantly contribute to breast cancer susceptibility in the analyzed sample from the Mexican population.

[Comparison of clinical outcomes of anterior cruciate ligament repair in the active military using allograft versus autograft, 2-year follow-up]. / Comparación de resultados clínicos de reparación de ligamento cruzado anterior en militares en el activo con uso de aloinjerto versus autoinjerto, seguimiento de 2 años.

INTRODUCTION: Due to the inherent activities of the active duty personnel of the Mexican Navy, ligament injuries are constant, particularly the anterior cruciate ligament of the knee (ACL). Currently, we have various techniques and resources for its repair. OBJECTIVE: identify the clinical results obtained in anterior cruciate ligament reconstruction in active military. MATERIAL AND METHODS: retrospective observational study comparing clinical outcomes of anterior cruciate ligament repair in active military with the use of allograft and autograft in 23 patients who met inclusion criteria for the surgical procedure from 2017 to 2019 at the Naval Medical Center. 23 patients (46 in total) were considered for each category of anterior cruciate ligament repair with autologous graft (contralateral patellar) and heterologous graft (cadaveric anterior cruciate ligament). With an average age of autologous (35.6 years), heterologous (35 years). BMI average: autologous (26.5), heterologous (26.5). Male gender in its entirety. The IKDC and Lysholm scales were applied to all patients for the evolution of subjective results of clinical improvement in a 2-year follow-up; where a significant difference (p = 0.0001) could be observed when comparing both anterior cruciate ligament reconstruction techniques. RESULTS: we included 46 patients who underwent anterior cruciate ligament reconstruction for indication of complete injury respectively by the Joint Surgery Service of the Naval Medical Center. A better level of clinical benefit was observed in patients with heterologous graft, both in evaluation by IKDC scale (median 95.52 ± 1.85) as in Lysholm scale (median 94.91 ± 1.62) compared to autologous grafts, IKDC (median 89.92 ± 2.55) and Lysholm (median 86.04 ± 5.58), with value of p = 0.0001 for both cases. CONCLUSIONS: The results our study suggests that a superiority of functionality is obtained as reported by patients in whom heterograft was used.

INTRODUCCIÓN: Debido a las actividades inherentes del personal del servicio activo de la Armada de México, son constantes las lesiones ligamentarias, en particular la lesión del ligamento cruzado anterior de la rodilla (LCA). Actualmente, contamos con diversas técnicas y recursos para su reparación. OBJETIVO: identificar los resultados clínicos obtenidos en reconstrucción de ligamento cruzado anterior en militares en el activo. MATERIAL Y MÉTODOS: estudio observacional retrospectivo donde se compararon los resultados clínicos de reparación de ligamento cruzado anterior en militares en el activo con uso de aloinjerto y autoinjerto en 46 pacientes que cumplieron criterios de inclusión para el procedimiento quirúrgico del año 2017 al 2019 en el Centro Médico Naval. Se incluyeron 23 pacientes para cada rubro de reparación de ligamento cruzado anterior con injerto autólogo (patelar contralateral) e injerto heterólogo (ligamento cruzado anterior cadavérico). A todos los pacientes se les aplicaron las escalas IKDC y Lysholm, para la evaluación de resultados subjetivos de mejoría clínica a un seguimiento de dos años. RESULTADOS: se reclutaron 46 pacientes que fueron sometidos a reconstrucción de ligamento cruzado anterior con aloinjerto o con autoinjerto. La media de edad por grupo fue: autólogo 35.6 años, heterólogo 35 años. Índice de masa corporal (IMC) promedio: autólogo 26.5, heterólogo 26.5. Sexo masculino en su totalidad. Se observó un mejor nivel de beneficio clínico en los pacientes con injerto heterólogo, tanto en evaluación por escala de IKDC (media 95.52 ± 1.85) como en escala de Lysholm (media 94.91 ± 1.62), en comparación con los injertos autólogos, IKDC (media 89.92 ± 2.55) y Lysholm (media 86.04 ± 5.58), con diferencia significativa (p = 0.0001) al comparar ambas técnicas de reconstrucción de ligamento cruzado anterior. CONCLUSIÓN: Los resultados de nuestro estudio sugieren que se obtiene una superioridad de funcionalidad referida por los pacientes en los que se utilizó heteroinjerto.

SOD1 gene variants rs4817415, rs2070424, and rs1041740 and their association with breast cancer risk.

OBJECTIVE: The aim of this investigation was to determine the frequency and association of the variants rs4817415, rs2070424, and rs1041740 of the SOD1 gene in healthy women and breast cancer (BC) patients. PATIENTS AND METHODS: Genomic DNA samples from 146 healthy women and 130 patients with BC were analyzed. RESULTS: GG genotype (OR 2.54, 95% CI 1.31-4.91, p = 0.0073) and the G allele (OR 1.37, 95% CI 1.09-1.73, p = 0.007) of the rs2070424 variant and CC genotype (OR 1.67, 95% CI 1.04-0.2.70, p = 0.0444) and allele C (OR 1.58, 95% CI 1.09-2.29, p = 0.0183) of the rs1041740 variant of SOD1 gene were associated as risk factors for BC susceptibility relative to the control group. Study groups comparison of the stratification by menopausal status showed an association of susceptibility to BC risk with carriers of the GG genotype (OR 2.9, 95% CI 1.11-7.81, p = 0.042) of the rs2070424 variant and with the premenopausal status of the study group and the TT (OR 2.89, 95% CI 1.73-4.85, p = 0.001) genotype of the rs1041740 variant. Furthermore, differences were observed in the patients with BC who were carriers of the CC genotype of the rs4817415 variant with elevated Ki-67 (≥ 20%) and who presented lymph node metastasis and stage III-IV BC (p<0.05). Two common haplotypes were identified in the study groups: CAC (protective factor), and CGC (risk factor) (p<0.05). CONCLUSIONS: The rs2070424 and rs1041740 variants of the SOD1 gene and the CGC haplotype were associated as risk susceptibility factors of BC in this sample analyzed.

The rs1008562, rs2234671, and rs3138060 polymorphisms of the CXCR1 gene are associated with breast cancer risk in a Mexican population.

OBJECTIVE: The rs1008562, rs2234671 and rs3138060 polymorphisms of the CXCR1 gene have been shown to be associated with many diseases, but in breast cancer (BC) their association has not been detected. The purpose of this study was to determine the frequency and association of the rs1008562, rs2234671 and rs3138060 polymorphisms of CXCR1 gene in BC patients in the Mexican population. PATIENTS AND METHODS: The CXCR1 polymorphisms were determined by Polymerase Chain Reaction (PCR) and real time-PCR in healthy Mexican subjects and BC patients. RESULTS: The prevalent patron in BC patients was observed, the majority were overweight and obesity (72%) with metastatic lymph nodes (48%), luminal A/B subtypes (63%), and advanced stages (60%). Triple negative breast cancer (TNBC) patients: they were younger (58%) than 43 years old, overweight (33%), obesity (42%), ductal type histological (98%), metastasis to lymph nodes (47%), advanced stages III-IV (61%) and metastasis (33%). The rs2234671 polymorphism was associated with BC susceptibility when BC patients and the control group were compared for the CC genotype (p=0.037), CG (heterozygous model: p=0.018), GC/CC (dominant model: p=0.004), and the C allele (p=0.001), as well as the GC/CC genotype with hormone replace therapy (HRT, p=0.016). The rs3138060 polymorphism was associated with BC susceptibility for CG/GG genotype (dominant model: p=0.032) and G allele (p=0.018). Although the association between the dominant model of rs1008562, rs2234671, rs3138060 polymorphisms and BC patients and control was evident for tobacco and alcohol consumption (p<0.05). The rs1008562, rs2234671, and rs3138060 polymorphisms of the CXCR1 gene classified by molecular subtype and stage were also associated with BC patients, indicating that these factors may significantly contribute to BC risk. The CCC (OR 1.75, 95% CI 1.03- 2.97, p=0.046), GGG (OR 3.73, 95% CI 1.61- 8.65, p=0.0018) haplotypes were also associated with BC susceptibility. CONCLUSIONS: Rs2234671 and rs3138060 polymorphisms in the CXCR1 gene were associated with BC susceptibility in the Mexican population. The dominant model of the rs1008562, rs2234671 and rs3138060 polymorphisms could significantly contribute to BC risk in tobacco and alcohol consumption, molecular subtype and stage. The rs1008562, rs2234671 and rs3138060 polymorphisms, and the haplotypes CCC and GGG could significantly contribute to BC risk in the Mexican population analyzed.

Comparación de resultados clínicos de reparación de ligamento cruzado anterior en militares en el activo con uso de aloinjerto versus autoinjerto, seguimiento de 2 años / Comparison of clinical outcomes of anterior cruciate ligament repair in the active military using allograft versus autograft, 2-year follow-up

Resumen: Introducción: Debido a las actividades inherentes del personal del servicio activo de la Armada de México, son constantes las lesiones ligamentarias, en particular la lesión del ligamento cruzado anterior de la rodilla (LCA). Actualmente, contamos con diversas técnicas y recursos para su reparación. Objetivo: identificar los resultados clínicos obtenidos en reconstrucción de ligamento cruzado anterior en militares en el activo. Material y métodos: estudio observacional retrospectivo donde se compararon los resultados clínicos de reparación de ligamento cruzado anterior en militares en el activo con uso de aloinjerto y autoinjerto en 46 pacientes que cumplieron criterios de inclusión para el procedimiento quirúrgico del año 2017 al 2019 en el Centro Médico Naval. Se incluyeron 23 pacientes para cada rubro de reparación de ligamento cruzado anterior con injerto autólogo (patelar contralateral) e injerto heterólogo (ligamento cruzado anterior cadavérico). A todos los pacientes se les aplicaron las escalas IKDC y Lysholm, para la evaluación de resultados subjetivos de mejoría clínica a un seguimiento de dos años. Resultados: se reclutaron 46 pacientes que fueron sometidos a reconstrucción de ligamento cruzado anterior con aloinjerto o con autoinjerto. La media de edad por grupo fue: autólogo 35.6 años, heterólogo 35 años. Índice de masa corporal (IMC) promedio: autólogo 26.5, heterólogo 26.5. Sexo masculino en su totalidad. Se observó un mejor nivel de beneficio clínico en los pacientes con injerto heterólogo, tanto en evaluación por escala de IKDC (media 95.52 ± 1.85) como en escala de Lysholm (media 94.91 ± 1.62), en comparación con los injertos autólogos, IKDC (media 89.92 ± 2.55) y Lysholm (media 86.04 ± 5.58), con diferencia significativa (p = 0.0001) al comparar ambas técnicas de reconstrucción de ligamento cruzado anterior. Conclusión: Los resultados de nuestro estudio sugieren que se obtiene una superioridad de funcionalidad referida por los pacientes en los que se utilizó heteroinjerto.

Abstract: Introduction: Due to the inherent activities of the active duty personnel of the Mexican Navy, ligament injuries are constant, particularly the anterior cruciate ligament of the knee (ACL). Currently, we have various techniques and resources for its repair. Objective: identify the clinical results obtained in anterior cruciate ligament reconstruction in active military. Material and methods: retrospective observational study comparing clinical outcomes of anterior cruciate ligament repair in active military with the use of allograft and autograft in 23 patients who met inclusion criteria for the surgical procedure from 2017 to 2019 at the Naval Medical Center. 23 patients (46 in total) were considered for each category of anterior cruciate ligament repair with autologous graft (contralateral patellar) and heterologous graft (cadaveric anterior cruciate ligament). With an average age of autologous (35.6 years), heterologous (35 years). BMI average: autologous (26.5), heterologous (26.5). Male gender in its entirety. The IKDC and Lysholm scales were applied to all patients for the evolution of subjective results of clinical improvement in a 2-year follow-up; where a significant difference (p = 0.0001) could be observed when comparing both anterior cruciate ligament reconstruction techniques. Results: we included 46 patients who underwent anterior cruciate ligament reconstruction for indication of complete injury respectively by the Joint Surgery Service of the Naval Medical Center. A better level of clinical benefit was observed in patients with heterologous graft, both in evaluation by IKDC scale (median 95.52 ± 1.85) as in Lysholm scale (median 94.91 ± 1.62) compared to autologous grafts, IKDC (median 89.92 ± 2.55) and Lysholm (median 86.04 ± 5.58), with value of p = 0.0001 for both cases. Conclusions: The results our study suggests that a superiority of functionality is obtained as reported by patients in whom heterograft was used.

Increased homocysteine plasma levels in breast cancer patients of a Mexican population.

AIM: Hyperhomocysteinemia has been associated with different pathologies, including cardiovascular diseases, hypertension, diabetes, and breast cancer (BC). To examine the differences in total homocysteine (tHcy) plasma levels, we compared healthy women to BC patients from a Mexican population. MATERIALS AND METHODS: The tHcy plasma levels were measured using high-performance liquid chromatography with a fluorescence detector in 89 female controls and 261 BC patients. RESULTS: The observed plasma tHcy levels were significantly higher among the BC patients (11.1019 ± 5.9161 µmol/l) compared to the controls (9.1046 ± 1.3213 µmol/l) (p = 0.002), and these differences were evident when stratified by age (≥ 50 years old), menopause status, overweight and obesity, miscarriages, node metastases, progression, subtype classification (luminal, Her2 and triple negative) and nonresponse to chemotherapy. CONCLUSIONS: The tHcy plasma levels could be a good marker for the progression and chemosensitivity of BC in the analyzed sample from a Mexican population.

Invasive lobular carcinoma of the breast with extracellular mucin: A case report.

BACKGROUND: Invasive lobular carcinoma is the second most common histological type of breast carcinoma, accounting for approximately 5%-15% of all invasive breast cancers. The extracellular mucin secretion is by default a feature of ductal carcinoma. Only four cases of infiltrative lobular carcinoma with extracellular mucin have been report. CASE SUMMARY: A 60 year old female asymptomatic patient with palpable breast mass and architectural distortion by mammography on external upper quadrant of the right breast was diagnosed as invasive lobular carcinoma with extracellular mucin in the resection, confirmed with immunohistochemistry markers. DISCUSSION: Previous report in the literature of four cases of Invasive lobular carcinoma of breast with extracellular mucin, all of them sharing the same histologic features: the presence of extracellular and intracellular mucin with appearance of infiltrates lobular carcinoma with signet ring cells and "Indian files". CONCLUSION: It is important to know that extracellular mucin production is not exclusive of ductal lesions and keep in mind the lobular carcinomas with extracellular mucin as a differential diagnosis.

Trends in use of anti-thrombotic agents and outcomes in patients with non-ST-segment elevation myocardial infarction (NSTEMI) managed with an invasive strategy.

OBJECTIVE: To analyze trends in utilization of anti-thrombotic agents (ATA) and in-hospital clinical outcomes in non-ST-elevation myocardial infarction (NSTEMI) patients managed with an invasive strategy from 2007 to 2010. METHODS & RESULTS: Using ACTION Registry(®)-GWTG™ data, we analyzed trends in use of ATA and in-hospital clinical outcomes among 64,199 NSTEMI patients managed invasively between 2007 and 2010. ATA included unfractionated heparin (UFH), low molecular weight heparin (LMWH), glycoprotein IIb/IIIa inhibitors (GPI) and bivalirudin. Although the proportion of NSTEMI patients treated with PCI within 48h of hospital arrival was similar in 2007 and 2010, percentage use of bivalirudin (13.4-27.3%; p<0.01) and UFH increased (60.0-67.5%, p<0.01), and that of GPI (62.3-41.0%; p<0.01) and LMWH (41.5-36.8%; p<0.01) declined. Excess dosing of UFH (75.9-59.3%, p<0.01), LMWH (9.6-5.2%; p<0.01) and GPI (8.9-5.9%, p<0.01) was also significantly lower in 2010 compared with 2007. Though in-hospital mortality rates were similar in 2007 and 2010 (2.3-1.9%, p=0.08), the rates of in-hospital major bleeding (8.7-6.6%, p<0.01) and non-CABG related RBC transfusion (6.3-4.6%, p<0.01) were significantly lower in 2010 compared with 2007. CONCLUSION: Compared with 2007, patients with NSTEMI, who were managed invasively in 2010 received GPI and LMWH less often and bivalirudin and UFH more frequently. There were sizeable reductions in the rates of excess dosing of UFH (though still occurred in 67% of patients), GPI and LMWH. In-hospital major bleeding complications and post-procedural RBC transfusion were lower in 2010 compared with 2007.

Point-of-care measured platelet inhibition correlates with a reduced risk of an adverse cardiac event after percutaneous coronary intervention: results of the GOLD (AU-Assessing Ultegra) multicenter study.

BACKGROUND: The optimal level of platelet inhibition with a glycoprotein (GP) IIb/IIIa antagonist necessary to minimize thrombotic complications in patients undergoing a percutaneous coronary intervention (PCI) is currently unknown. METHODS AND RESULTS: Five hundred patients undergoing a PCI with the planned use of a GP IIb/IIIa inhibitor had platelet inhibition measured at 10 minutes, 1 hour, 8 hours, and 24 hours after the initiation of therapy with the Ultegra Rapid Platelet Function Assay (Accumetrics). Major adverse cardiac events (MACES: composite of death, myocardial infarction, and urgent target vessel revascularization) were prospectively monitored, and the incidence correlated with the measured level of platelet function inhibition at all time points. One quarter of all patients did not achieve >/=95% inhibition 10 minutes after the bolus and experienced a significantly higher incidence of MACEs (14.4% versus 6.4%, P=0.006). Patients whose platelet function was <70% inhibited at 8 hours after the start of therapy had a MACE rate of 25% versus 8.1% for those >/=70% inhibited (P=0.009). By multivariate analysis, platelet function inhibition >/=95% at 10 minutes after the start of therapy was associated with a significant decrease in the incidence of a MACE (odds ratio 0.46, 95% CI 0.22 to 0.96, P=0.04). CONCLUSIONS: Substantial variability in the level of platelet function inhibition is achieved with GP IIb/IIIa antagonist therapy among patients undergoing PCI. The level of platelet function inhibition as measured by a point-of-care assay is an independent predictor for the risk of MACEs after PCI.

Long-term clinical events following creatine kinase--myocardial band isoenzyme elevation after successful coronary stenting.

OBJECTIVE: We sought to evaluate the impact of intermediate creatine kinase-myocardial band isoenzyme (CK-MB) elevation on late clinical outcomes in patients undergoing successful stent implantation in native coronary arteries. BACKGROUND: Elevations of CK-MB after percutaneous coronary interventions are frequent. An association between high level of CK-MB elevation (>5 times normal) and late mortality after balloon and new device angioplasty has been reported previously. However, significant controversy remains on the long-term clinical importance of lower CK-MB elevations (one to five times normal) after percutaneous coronary revascularization. Moreover, the incidence and prognostic importance of cardiac enzyme elevation after coronary stenting have not been well established. METHODS: Prospectively collected data from 900 consecutive patients (1,213 lesions) undergoing successful stenting in native vessels were analyzed. Based on the CK-MB levels after coronary stenting, patients were classified into three groups: normal group 1 (n = 585), elevation of >1 to 5 times normal group 2 (n = 238) and elevation of >5 times normal group 3 (n = 77). RESULTS: Patients in group 3 had more in-hospital recurrent ischemia (p = 0.001) and pulmonary edema (p = 0.01) than patients in groups 1 and 2. Long-term clinical end points were similar between groups 1 and 2. However, patients in group 3 had an increased incidence of late mortality compared with patients in groups 2 and 1 (6.9%, 1.2% and 1.7%, respectively, p = 0.01). Multivariate analysis showed that patients with CK-MB >5 times normal after coronary stenting had an increased risk of major adverse clinical events (relative risk: 1.70, p < 0.05) and death (relative risk: 3.25, p < 0.05) that was not observed in patients with lower CK-MB rise. CONCLUSIONS: Patients with CK-MB elevation >5 times normal had higher late mortality and more unfavorable event-free survival than those patients with normal or lower CK-MB rise after coronary stenting. While intermediate CK-MB elevation (>1 to 5 times normal) is frequent after coronary stenting (26%), this was not associated with an increased risk of late mortality or major adverse clinical events.

Percutaneous coronary intervention versus coronary artery bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass: a multicenter, randomized trial. Investigators of the Department of Veterans Affairs Cooperative Study #385, the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME).

BACKGROUND: Percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) are being applied to high-risk populations, but previous randomized trials comparing revascularization methods have excluded a number of important high-risk groups. OBJECTIVES: This five-year, multicenter, randomized clinical trial was designed to compare long-term survival among patients with medically refractory myocardial ischemia and a high risk of adverse outcomes assigned to either a CABG or a PCI strategy, which could include stents. METHODS: Patients from 16 Veterans Affairs Medical Centers were screened to identify myocardial ischemia refractory to medical management and the presence of one or more risk factors for adverse outcome with CABG, including prior open-heart surgery, age >70 years, left ventricular ejection fraction <0.35, myocardial infarction within seven days or intraaortic balloon pump required. Clinically eligible patients (n = 2,431) underwent coronary angiography; 781 were angiographically acceptable; 454 (58% of eligible) patients consented to random assignment between CABG and PCI. RESULTS: A total of 232 patients was randomized to CABG and 222 to PCI. The 30-day survivals for CABG and PCI were 95% and 97%, respectively. Survival rates for CABG and PCI were 90% versus 94% at six months and 79% versus 80% at 36 months (log-rank test, p = 0.46). CONCLUSIONS: Percutaneous coronary intervention is an alternative to CABG for patients with medically refractory myocardial ischemia and a high risk of adverse outcomes with CABG.

Impact of the Duett sealing device on quality of life and hospitalization costs for coronary diagnostic and interventional procedures: Results from the Study of Economic and Quality of Life substudy of the SEAL trial.

BACKGROUND: The Simple and Effective Arterial Closure (SEAL) trial examined the safety and effectiveness of the Duett vascular sealing device (Vascular Solutions, Minneapolis, Minn) versus manual compression after diagnostic and interventional coronary procedures. We compared quality of life and initial hospitalization costs among patients treated with the Duett device versus manual compression. METHODS: Functional status was assessed with the Duke Activity Status Index (DASI) at 7 and 30 days after intervention. General health status was assessed with the Short Form (SF-36) at 30 days after intervention. Hospitalization costs were derived from the UB92 formulation of the hospital bill. RESULTS: There was a strong trend toward higher functional status in patients receiving treatment with the Duett device at 7 days both before (P =.04) and after (P =.08) adjustment for significant covariates. This difference was significant in the diagnostic group but not in the interventional group. No significant differences in quality of life between the Duett device and manual compression at 30 days were found. There was no significant difference in total hospitalization costs between treatment arms (P =.91). For interventional patients, mean total in-hospital costs were $10,167 in the Duett group and $10,225 in the manual compression group (P =.82). For diagnostic patients, mean hospitalization costs were $7784 and $7996 for the Duett device and manual compression groups, respectively (P =.72). Trends toward reduced recovery/observation room costs with the Duett device (P =.06) were found; this difference was significant in the diagnostic group ($198 vs $279, P =.02). CONCLUSIONS: The Duett sealing device was associated with significantly higher functional status at 7 days after the procedure in addition to shortened time to hemostasis and ambulation, with no associated increase in cost.