Predictors of Secondhand Smoke Exposure During Pregnancy in Costa Rica, the Dominican Republic, and Honduras.

INTRODUCTION: Secondhand smoke (SHS) exposure poses risks to pregnant women and children. Though smoking among pregnant women in many low- and middle-income countries is low, exposure to SHS might be higher. We examined the prevalence and predictors of SHS among pregnant women from Costa Rica, the Dominican Republic, and Honduras. METHODS: Postpartum women 18+ years old who completed pregnancy in past 5 years were surveyed in health care and community settings. RESULTS: Data for 1,081 women indicated low tobacco use (1.0%-3.7%), frequent exposure to active smokers (29.0%-34.0%), often being close enough to breathe others' smoke (49.4%-66.5%), and most having smoke-free home policies (70.8%-76.2%). Women reporting unintended pregnancy (adjusted odds ratio [aOR]: 1.44, 95% confidence interval [CI] 1.03, 2.00) and alcohol consumption (aOR: 1.92, 95% CI 1.34, 2.77) were more likely to be close enough to breathe others' smoke. Women with health problems during pregnancy (aOR: 1.48 95% CI 1.07, 2.06) were more likely to have home smoking policies. Tobacco use was associated with all SHS exposure outcomes. CONCLUSIONS: SHS exposure was high during pregnancy; women with higher risk variables, that is, tobacco use, alcohol consumption, and unintended pregnancy were more likely to be exposed. Addressing SHS exposure in pregnancy in low- and middle-income countries can improve maternal health outcomes in vulnerable populations. IMPLICATIONS: The study results suggest a cluster of multiple risk factors associated with a high prevalence of exposure to SHS among pregnant women in LIMCs from Latin America and Caribbean Region. Interventions, regulations, and policies need to address specific high-risk factors to change behaviors and improve maternal and child health outcomes especially in vulnerable populations.

Antimicrobial resistance profiles of microorganisms isolated from hospitalized patients in Dominican Republic.

OBJECTIVE: To define the antimicrobial resistance profiles of the microorganisms most commonly isolated from hospitalized adult patients in Dominican Republic (DR). METHODS: A retrospective, cross-sectional study of phenotypic antimicrobial susceptibility patterns was conducted using data from 3 802 clinical microbiology reports specifying positive bacterial cultures in samples collected from patients admitted to the clinical, surgery, and intensive care units (ICU) at three tertiary-level care hospitals in the city of Santiago de los Caballeros from 1 January 2016 - 31 December 2017. Descriptive statistics and chi-square test (P ≤ 0.05) were used to analyze the qualitative variables. RESULTS: At the three hospitals, there were 932, 1 090, and 1 780 microbiology reports analyzed. Of the total, 1274 were from the ICU, 1 042 from the surgery unit, and 1 486 from the clinical unit. Methicillin resistance was found in 57.3% of the Staphylococcus aureus isolates and 75.3% of the coagulase-negative staphylococci. Third-generation cephalosporin resistance was detected in 54.4% of isolates identified as members of the Enterobacteriaceae family, 67.3% of the Acinetobacter spp., and 91.7% of the Pseudomonas, while carbapenem resistance was shown by 8.0%, 23.8%, and 51.0% of these, respectively. Most of the resistant Acinetobacter spp. isolates were found in just one hospital and the prevalence of Enterobacteriaceae resistant to carbapenems was highest in the ICU. CONCLUSION: Antimicrobial resistance levels are high among hospitalized patients in Dominican Republic and may cause enhanced risk factors that impact clinical outcomes. Urgent measures are needed to address antimicrobial resistance in DR.

Combinatory effect of BRCA1 and HERC2 expression on outcome in advanced non-small-cell lung cancer.

BACKGROUND: BRCA1 is a main component of homologous recombination and induces resistance to platinum in preclinical models. It has been studied as a potential predictive marker in lung cancer. Several proteins modulate the function of BRCA1. The E3 ubiquitin ligase HERC2 facilitates the assembly of the RNF8-UBC13 complex to recruit BRCA1 to DNA damage sites. The combined analysis of multiple components of the pathway leading to the recruitment of BRCA1 at DNA damage sites has the potentiality to improve the BRCA1 predictive model. METHODS: We retrospectively analyzed 71 paraffin-embedded tumor samples from advanced non-small-cell lung cancer patients treated with first-line platinum based chemotherapy and measured the mRNA expression levels of BRCA1, RNF8, UBC13 and HERC2 using real-time PCR. The mRNA expression was categorized using median value as cut-off point. RESULTS: The median progression-free survival of all 71 patients was 7.2 months whereas the median overall survival of the study population was 10.7 months. Among patients with low BRCA1 expression, the median PFS was 7.4 months in the presence of low HERC2 levels and 5.9 months for patients expressing high HERC2 levels (p = 0.01). The median OS was 15.3 months for patients expressing low levels of both genes and 7.4 months for those with low BRCA1 but high HERC2 (p = 0.008). The multivariate analysis showed that among patients with Eastern Cooperative Oncology Group performance status 0-1, the combined low expression of both BRCA1 and HERC2 clearly reduced the risk of progression (p = 0.03) and of death (p = 0.004). CONCLUSIONS: These findings confirm the potentiality of integrated DNA repair components analysis in predicting the sensitivity to platinum in lung cancer. The study indicates a predictive role for HERC2 mRNA expression and paves the way for further refinement of the BRCA1 predictive model.

Stroke Awareness Is Worse among the Old and Poorly Educated: A Population-Based Survey.

BACKGROUND: This article surveys a representative sample of adults to assess their knowledge of stroke, its vascular risk factors and warning symptoms, illness perception, and attitude toward strokes. METHODS: A representative sample of the region population was selected using a double randomization design. Previously trained medical students carried out face-to-face interviews using a structured questionnaire with open- and closed-ended questions. RESULTS: In all, 2411 subjects were interviewed. Seventy-three percent reported at least 1 correct warning sign of stroke, whereas only 12.2% reported 3. The most frequently mentioned were sudden weakness, dizziness, and headache. Only 59.2% named at least 1 correct risk factor for stroke. Smoking and hypertension were mainly named. Forty percent of the respondents demonstrated adequate knowledge of stroke. Tellingly, prevalence of adequate knowledge was significantly lower in subjects with previous stroke (29.3% [95% confidence interval {CI}, 19.7-40.3], P = .049), hypertension (35.0% [95% CI, 31.1-39.1], P = .009), diabetes (31.9% [95% CI, 25.9-38.3], P = .011), hypercholesterolemia (35.8% [95% CI, 31.8-39.9], P = .03), and obesity (28.2% [95% CI, 23.8-33.0], P < .001). Illness perception was generally correct. In the final logistic regression model, younger age, urban area of residence, higher educational level, higher family income, normal pressure, normal weight, and family history of stroke were associated with adequate knowledge of stroke. CONCLUSIONS: Basic knowledge of stroke is insufficient among the general population of Extremadura. There is a discrepancy between theoretical stroke knowledge and illness perception. These findings have implications for public health initiatives for stroke.

Generalizability of Tau and Amyloid Plasma Biomarkers in Alzheimer's Disease Cohorts of Diverse Genetic Ancestries.

Introduction: Plasma phosphorylated threonine-181 of Tau and amyloid beta are biomarkers for differential diagnosis and preclinical detection of Alzheimer disease (AD). Given differences in AD risk across diverse populations, generalizability of existing biomarker data is not assured. Methods: In 2,086 individuals of diverse genetic ancestries (African American, Caribbean Hispanic, and Peruvians) we measured plasma pTau-181 and Aß42/Aß40. Differences in biomarkers between cohorts and clinical diagnosis groups and the potential discriminative performance of the two biomarkers were assessed. Results: pTau-181 and Aß42/Aß40 were consistent across cohorts. Higher levels of pTau181 were associated with AD while Aß42/Aß40 had minimal differences. Correspondingly, pTau-181 had greater predictive value than Aß42/Aß40, however, the area under the curve differed between cohorts. Discussion: pTau-181 as a plasma biomarker for clinical AD is generalizable across genetic ancestries, but predictive value may differ. Combining genomic and biomarker data from diverse individuals will increase understanding of genetic risk and refine clinical diagnoses.

Screening for epidermal growth factor receptor mutations in lung cancer.

BACKGROUND: Activating mutations in the epidermal growth factor receptor gene (EGFR) confer hypersensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in patients with advanced non-small-cell lung cancer. We evaluated the feasibility of large-scale screening for EGFR mutations in such patients and analyzed the association between the mutations and the outcome of erlotinib treatment. METHODS: From April 2005 through November 2008, lung cancers from 2105 patients in 129 institutions in Spain were screened for EGFR mutations. The analysis was performed in a central laboratory. Patients with tumors carrying EGFR mutations were eligible for erlotinib treatment. RESULTS: EGFR mutations were found in 350 of 2105 patients (16.6%). Mutations were more frequent in women (69.7%), in patients who had never smoked (66.6%), and in those with adenocarcinomas (80.9%) (P<0.001 for all comparisons). The mutations were deletions in exon 19 (62.2%) and L858R (37.8%). Median progression-free survival and overall survival for 217 patients who received erlotinib were 14 months and 27 months, respectively. The adjusted hazard ratios for the duration of progression-free survival were 2.94 for men (P<0.001); 1.92 for the presence of the L858R mutation, as compared with a deletion in exon 19 (P=0.02); and 1.68 for the presence of the L858R mutation in paired serum DNA, as compared with the absence of the mutation (P=0.02). The most common adverse events were mild rashes and diarrhea; grade 3 cutaneous toxic effects were recorded in 16 patients (7.4%) and grade 3 diarrhea in 8 patients (3.7%). CONCLUSIONS: Large-scale screening of patients with lung cancer for EGFR mutations is feasible and can have a role in decisions about treatment.

Detection of EGFR mutations with mutation-specific antibodies in stage IV non-small-cell lung cancer.

BACKGROUND: Immunohistochemistry (IHC) with mutation-specific antibodies may be an ancillary method of detecting EGFR mutations in lung cancer patients. METHODS: EGFR mutation status was analyzed by DNA assays, and compared with IHC results in five non-small-cell lung cancer (NSCLC) cell lines and tumor samples from 78 stage IV NSCLC patients. RESULTS: IHC correctly identified del 19 in the H1650 and PC9 cell lines, L858R in H1975, and wild-type EGFR in H460 and A549, as well as wild-type EGFR in tumor samples from 22 patients. IHC with the mAb against EGFR with del 19 was highly positive for the protein in all 17 patients with a 15-bp (ELREA) deletion in exon 19, whereas in patients with other deletions, IHC was weakly positive in 3 cases and negative in 9 cases. IHC with the mAb against the L858R mutation showed high positivity for the protein in 25/27 (93%) patients with exon 21 EGFR mutations (all with L858R) but did not identify the L861Q mutation in the remaining two patients. CONCLUSIONS: IHC with mutation-specific mAbs against EGFR is a promising method for detecting EGFR mutations in NSCLC patients. However these mAbs should be validated with additional studies to clarify their possible role in routine clinical practice for screening EGFR mutations in NSCLC patients.

Management experience of advanced-stage mycosis fungoides/Sézary syndrome: a retrospective study from Spanish haematology referral units.

BACKGROUND: Advanced-stage mycosis fungoides/Sézary syndrome (aMF/SS) has a dismal outcome. The only curative treatment is allogeneic stem cell transplantation (allo-SCT) but this is limited to selected candidates, thus palliative therapy is the most frequent strategy. OBJECTIVES: To describe the characteristics of aMF/SS in cases referred to haematology units for advanced/palliative therapy. MATERIALS AND METHODS: Data from 30 patients were collected from four centres, and descriptive statistics, frequencies and survival analyses were calculated. RESULTS: Eighty-eight per cent of patients received systemic therapy. The median number of therapies was three (range: 1-9). Bexarotene (21%), CHOP-like chemotherapy (10%) and methotrexate (9%) were the more common treatments. The overall survival at a median follow-up of 28 months (range: 8-65 months) for aMF/SS was 56.9%. Survival probability was more favourable for MF (p < 0.02). Nine patients received allo-SCT. Half of the patients (56%) relapsed after allo-SCT but could be rescued with immunosuppression tapering, donor lymphocyte infusions and additional therapy (80%). CONCLUSION: There is significant heterogeneity in aMF/SS treatments. Survival is more favourable for MF compared to SS. Current chemoimmunotherapies are insufficient to control disease, making allo-SCT the best therapeutic approach in selected patients.

XPG mRNA expression levels modulate prognosis in resected non-small-cell lung cancer in conjunction with BRCA1 and ERCC1 expression.

BACKGROUND: Molecular markers can help identify patients with early-stage non-small-cell lung cancer (NSCLC) with a high risk of relapse. Excision repair cross-complementing 1 (ERCC1), Xeroderma pigmentosum group G (XPG), and breast cancer 1 (BRCA1) are involved in DNA damage repair, whereas ribonucleotide reductase M1 (RRM1) is implicated in DNA synthesis. Expression levels of these molecules might therefore have a prognostic role in lung cancer. PATIENTS AND METHODS: We examined ERCC1, RRM1, XPG, and BRCA1 mRNA levels by real-time quantitative polymerase chain reaction in 54 patients with stage IB-IIB resected NSCLC. A strong correlation was observed between the 4 genes. RESULTS: For patients with low BRCA1, regardless of XPG mRNA expression levels, disease-free survival (DFS) was not reached. For patients with intermediate/high BRCA1 and high XPG, DFS was 50.7 months. However, for patients with intermediate/high BRCA1 and low/intermediate XPG, DFS decreased to 16.3 months (P = .002). Similar differences were observed in overall survival, with median survival not reached for patients with low BRCA1, regardless of XPG levels, or for patients with intermediate/high BRCA1 and high XPG. Conversely, for patients with intermediate/high BRCA1 levels and low/intermediate XPG levels, median survival dropped to 25.5 months (P = .007). CONCLUSION: BRCA1 and XPG were identified as independent prognostic factors for both median survival and DFS. High BRCA1 mRNA expression confers poor prognosis in early NSCLC, and the combination of high BRCA1 and low XPG expression still further increases the risk of shorter survival. These findings can help optimize the customization of adjuvant chemotherapy.

Three-gene expression signature predicts survival in early-stage squamous cell carcinoma of the lung.

PURPOSE: Adjuvant treatment may improve survival in early-stage squamous cell carcinoma (SCC) of the lung; however, the absolute gain is modest and mainly limited to stage II-IIIA. Current staging methods are imprecise indications of prognosis, but high-risk patients can be identified by gene expression profiling and considered for adjuvant therapy. EXPERIMENTAL DESIGN: The expression of 29 genes was assessed by reverse transcriptase quantitative PCR in frozen primary tumor specimens obtained from 66 SCC patients who had undergone surgical resection. Expression values were dichotomized using the median as a cutoff value. We used a risk score to develop a gene expression model for the prediction of survival. RESULTS: The univariate analysis of gene expression in the training cohort identified 10 genes with significant prognostic value: CSF1, EGFR, CA IX, PH4, KIAA0974, ANLN, VEGFC, NTRK1, FN1, and INR1. In the multivariate Cox model, CSF1 (hazard ratio, 3.5; P = 0.005), EGFR (hazard ratio, 2.7; P = 0.02), CA IX (hazard ratio, 0.2; P < 0.0001), and tumor size >4 cm (hazard ratio, 2.7; P = 0.02) emerged as significant markers for survival. The high prognostic value of a risk score based on the expression of the three genes (CSF1, EGFR, and CA IX) was positively validated in a separate cohort of 26 patients in an independent laboratory (P = 0.05). CONCLUSIONS: The three-gene signature is strongly associated with prognosis in early-stage SCC. Positive independent validation suggests its suitability for selecting SCC patients with an increased risk of death who might benefit from adjuvant treatment.

[Validity and applicability of the mnemonic POUNDing rule in patients with migraine. A descriptive study]. / Estudio descriptivo de validez y aplicabilidad de la regla nemotécnica POUNDing en pacientes con migraña.

INTRODUCTION: In assessing the patient with headache, clinicians are often faced with 2 important questions: Is this headache a migraine? Does this patient require neuroimaging? The aim of this study was to assess the validity and applicability of the mnemonic POUNDing rule in patients diagnosed with migraine. PATIENTS AND METHODS: A descriptive, validation study of the POUNDing rule in patients with a diagnosis of migraines and with a brain imaging test (computed tomography or magnetic resonance imaging), in an urban health centre and a neurology clinic of the University Hospital of Badajoz. RESULTS: A total of 116 patients were included (mean age 45.6 years; 79.3% women, 70 from the neurology clinics, and 46 from the health centre). The best validity parameters of the POUNDing rule were its positive predictive values: 90.9% (95% CI: 57.1-99.5%), 100% (95% CI: 73.2-99.3%), and 96.0% (95% CI: 77.7-99.8%) in the patients of the neurology clinic, the health centre and in the total population, respectively, and its low negative predictive values: 6.8% (95% CI: 2.2-17.3%), 3.1% (95% CI: 0.2-18.0%), and 5.5% (95% CI: 2.0-12.9%), also respectively in the patients of the neurology clinic, the health centre and in the total population. CONCLUSIONS: The POUNDing mnemonic rule has a high positive predictive values and can be a great help in accepting or rejecting a diagnosis of migraine, facilitating a more efficient use of neuroimaging tests.

Estudio cualitativo del uso de los cigarrillos electrónicos en los estudiantes universitarios / Qualitative Study of E-Cigarette Use in College Students

Objetivos: El propósito de esta investigación fue determinar el nivel de conocimiento, creencias, percepción y practicas asociadas al consumo de cigarrillos electrónicos en los estudiantes universitarios (UASD), recinto Santiago, República Dominicana. Cada estudiante firmó un consentimiento informado certificando que éste respondió cada pregunta realizada por el entrevistador de manera voluntaria. El método de recolección de los datos fue mediante entrevistas, las cuales fueron grabadas por los entrevistadores. La muestra fue de 53 entrevistas, 48 individuales y 5 grupos focales, la misma se tomó hasta alcanzar el punto de saturación de cada pregunta, es decir cuando todas las respuestas se tornaron repetitivas. Materiales y métodos: Se realizó un estudio cualitativo de tipo fenomenológico y de fuentes primarias en el período mayo-agosto del año 2019 en la universidad privada Pontificia Universidad Católica Madre y Maestra (PUCMM) y la universidad pública Universidad Autónoma de Santo Domingo. (UASD), campus Santiago, República Dominicana. El método de recolección de datos se realizó a través de entrevistas, las cuales fueron grabadas por los entrevistadores. Cada estudiante entrevistado firmó un consentimiento informado certificando que respondió voluntariamente a cada pregunta formulada por el entrevistador. La muestra estuvo compuesta por 53 entrevistas, 48 personas y cinco grupos focales. Las entrevistas se realizaron hasta llegar al punto de saturación de cada pregunta, que es cuando todas las respuestas se volvieron repetitivas. Resultados: El conocimiento que tiene los estudiantes universitarios sobre cigarrillo electrónico (CE), es pobre, desde su funcionamiento, partes, sustancias e incluso las posibles complicaciones que puede traer a la salud, tanto en la Pontificia Universidad Católica Madre y Maestra (PUCMM) como en la Universidad Autónoma de Santo Domingo (UASD), pero es más notable en la universidad pública. Por otro lado, muchos perciben el CE, como una alternativa del uso de tabaco, que posee diversidad de sabores, olor agradable, atractivo, práctico y capaz de ofrecer relajación. En cuanto a la actitud hacia el dispositivo, en PUCMM exhibe un mayor nivel de rechazo con respecto al uso. Es importante mencionar, que mayoría de los entrevistados son o alguna vez fueron usuarios de este, no obstante, no lo recomiendan en gran medida, ya que asumen que puede causar daño y ser adictivo, aunque en menor medida al cigarrillo convencional. La población más susceptible a su uso, son los jóvenes y el sexo masculino, aunque las féminas se han ido sumando de manera significativa. De igual modo, se logró apreciar las grandes influencias que mueven a los jóvenes a su consumo, incluyendo, las redes sociales, familia, amigos, en general el entorno en que se rodean. Conclusión: Concluimos que los estudiantes universitarios carecen de conocimiento con respecto al cigarrillo electrónico, tanto en el funcionamiento, sustancias y complicaciones para la salud. Muchos observan al cigarrillo electrónico como un dispositivo para fumar con un olor agradable, por lo cual puede ser muy atractivo para los usuarios. Se logró apreciar el importante papel que juegan las influencias sociales para el uso del dispositivo, promovido por las redes sociales y relaciones cercanas. Otro problema en la sociedad actual es el uso de CE en menores de edad. Según los resultados existe una gran necesidad de intervención y educación, principalmente en los jóvenes.

Objective: The purpose of this research was to determine the level of knowledge, beliefs, perception, and practices associated with consuming electronic cigarettes among university students. Materials and methods: A qualitative study of phenome-nological type and from primary sources was carried out in the period of May-August of the year 2019 at the private university Pontificia Universidad Católica Madre y Mae-stra (PUCMM) and the public university Universidad Autónoma de Santo Domingo (UASD), Santiago campus, Dominican Republic. The data collection method was done through interviews, which the interviewers recorded. Each student interviewed signed an informed consent cer-tifying that they answered voluntarily each question asked by the interviewer. The sample consisted of 53 interviews, 48 individuals, and five focus groups. Interviews were done until reaching the saturation point of each question, which is when all the answers became repetitive. Results: University students' knowledge regarding elec-tronic cigarettes (EC) is poor. Knowledge regarding its mechanism, parts, substances, and possible complications to one's health, is scarce both in PUCMM and the UASD, but this is more notable at the public university. Addition-ally, many perceive EC as an alternative to tobacco use, the former, as per our study population, having a variety of fla-vors, a pleasant smell, being attractive, practical, and capa-ble of offering relaxation. Regarding the attitude towards the device, PUCMM exhibits a higher level of rejection regarding its use. It is essential to mention that most inter-viewees were once users of EC. However, they do not rec-ommend it to a great extent since they assume that it can cause harm and be addictive, although to a lesser extent than conventional cigarettes. The population most suscep-tible to its use are young people, including minors and the male gender, although females have been significantly increasing its use. Similarly, it was possible to appreciate the influences that greatly evoke the younger population's consumption, including social networks, family, friends, and the surrounding environment. Conclusion: We concluded that university students have insufficient knowledge regarding electronic cigarettes, both in their mechanism, substances, and health compli-cations. Most see electronic cigarettes as smoking devices with a pleasant smell, which can be very attractive to users. It was possible to observe the critical role played by social influences on the use of the device, promoted by social networks and close relationships. Another problem in cur-rent society is the use of CE in minors. According to the results, there is a great need for intervention and educa-tion, mainly among the younger generation.

High BIM mRNA levels are associated with longer survival in advanced gastric cancer.

Chemotherapy drugs, including 5-fluorouracil (5-FU), oxaliplatin and docetaxel, are commonly used in the treatment of gastric cancer (GC). Apoptosis-relevant genes may be associated with drug resistance. In the present study, the messenger RNA (mRNA) expression levels of B-cell lymphoma 2 interacting mediator of cell death (BIM), astrocyte elevated gene-1 (AEG-1) and AXL receptor tyrosine kinase (AXL) were investigated in 131 advanced GC samples, and the expression levels of these genes were correlated with patients' overall survival (OS). All 131 patients received first-line FOLFOX combination chemotherapy with folinic acid and 5-FU, in which 56 patients were further treated with second-line docetaxel-based chemotherapy. A correlation between the mRNA expression levels of BIM and AEG-1 was observed (rs=0.30; P=0.002). There was no association between the mRNA expression levels of any of the individual genes analyzed and OS in patients only receiving first-line FOLFOX chemotherapy. In a subgroup of patients receiving docetaxel-based second-line chemotherapy, those with high or intermediate levels of BIM exhibited a median OS of 18.2 months [95% confidence interval (CI), 12.8-23.6], compared with 9.6 months (95% CI, 8.9-10.3) in patients with low BIM levels (P=0.008). However, there was no correlation between the mRNA expression levels of AEG-1 or AXL and OS. The risk of mortality was higher in patients with low BIM mRNA levels than in those with high or intermediate BIM mRNA levels (hazard ratio, 2.61; 95% CI, 1.21-5.62; P=0.010). Therefore, BIM may be considered as a biomarker to identify whether patients could benefit from docetaxel-based second-line chemotherapy in GC.

Impact of treatment in long-term survival patients with follicular lymphoma: A Spanish Lymphoma Oncology Group registry.

BACKGROUND: Follicular lymphoma is the second most common non-Hodgkin lymphoma in the United States and Europe. However, most of the prospective randomized studies have very little follow-up compared to the long natural history of the disease. The primary aim of this study was to investigate the long-term survival of our series of patients with follicular lymphoma. PATIENTS AND METHODS: A total of 1074 patients with newly diagnosed FL were enrolled. Patients diagnosed were prospectively enrolled from 1980 to 2013. RESULTS: Median follow-up was 54.9 months and median overall survival is over 20 years in our series. We analyzed the patients who are still alive beyond 10 years from diagnosis in order to fully assess the prognostic factors that condition this group. Out of 166 patients who are still alive after more than 10 years of follow-up, 118 of them (73%) are free of evident clinical disease. Variables significantly associated with survival at 10 years were stage < II (p <0.03), age < 60 years (p <0.0001), low FLIPI (p <0.002), normal ß2 microglobulin (p <0.005), no B symptoms upon diagnosis (p <0.02), Performance Status 0-1 (p <0.03) and treatment with anthracyclines and rituximab (p <0.001), or rituximab (p <0.0001). CONCLUSIONS: A longer follow-up and a large series demonstrated a substantial population of patients with follicular lymphoma free of disease for more than 10 years.

14-3-3sigma methylation in pretreatment serum circulating DNA of cisplatin-plus-gemcitabine-treated advanced non-small-cell lung cancer patients predicts survival: The Spanish Lung Cancer Group.

PURPOSE: Survival in patients with advanced non-small-cell lung cancer (NSCLC) who are treated with platinum-based chemotherapy is rather variable. Methylation-dependent transcriptional silencing of 14-3-3sigma, a major G2-M checkpoint control gene, could be a predictor of longer survival. PATIENTS AND METHODS: A sensitive methylation-specific polymerase chain reaction assay was used to evaluate 14-3-3sigma methylation status in pretreatment serum DNA obtained from 115 cisplatin-plus-gemcitabine-treated advanced NSCLC patients. RESULTS: 14-3-3sigma methylation was observed in all histologic types of 39 patients (34%). After a median follow-up of 9.8 months, median survival was significantly longer in the methylation-positive group (15.1 v 9.8 months; P = .004). Median time to progression was 8 months in the methylation-positive group and 6.3 months in the methylation-negative group (log-rank test, P = .027). A multivariate Cox regression model identified only 14-3-3sigma methylation status and Eastern Cooperative Oncology Group performance status as independent prognostic factors for survival. In an exploratory analysis, median survival for 22 methylation-positive responders has not been reached, whereas survival was 11.3 months for 29 methylation-negative responders (P = .001). CONCLUSION Methylation of 14-3-3sigma is a new independent prognostic factor for survival in NSCLC patients receiving platinum-based chemotherapy. It can be reliably and conveniently detected in the serum, thus obviating the need for tumor tissue analysis.

Analysis of c-kit expression in small cell lung cancer: prevalence and prognostic implications.

c-kit, a growth factor receptor with tyrosine kinase activity, plays an important role in the biology of cancer. Its expression has been documented in several malignancies. We performed a retrospective study in 85 patients diagnosed with small cell lung cancer (SCLC) to determine the prevalence and role of c-kit as a possible prognostic marker in this lung cancer malignancy. Demographic and clinical data were obtained from patient charts. c-kit, analyzed as immunohistochemical expression in paraffin-embedded tumour tissues, was observed in 60% of patients. All patients were former or present smokers. At diagnosis, 46% of the patients had limited disease (LD) and 54% extended disease (ED). c-kit expression was observed in 59% of LD and 61% of ED patients (p=0.4). Patients received a median of 4 cycles first-line combination chemotherapy (platinum and etoposide). In LD patients, time to progression (TTP) was 11.5 months in c-kit (+) versus 5.9 in c-kit (-) patients (p=0.14), and median survival 15.4 and 12.8 months, respectively (p=0.33). In the ED group, TTP was 5.5 months in c-kit (+) versus 3.8 in c-kit (-) patients (p=0.34), whereas median survival was 6.3 and 7.9 months, respectively (p=0.45). With the limited number of patients in mind, our findings tended towards an association between c-kit expression and survival in the LD group.

Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas.

PURPOSE: Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) confer a strong sensitivity to gefitinib, a selective tyrosine kinase inhibitor of EGFR. EXPERIMENTAL DESIGN: We examined EGFR mutations at exons 18, 19, and 21 in tumor tissue from 68 gefitinib-treated, chemorefractory, advanced non-small cell lung cancer patients from the United States, Europe, and Asia and in a highly gefitinib-sensitive non-small cell lung cancer cell line and correlated their presence with response and survival. In addition, in a subgroup of 28 patients for whom the remaining tumor tissue was available, we examined the relationship among EGFR mutations, CA repeats in intron 1 of EGFR, EGFR and caveolin-1 mRNA levels, and increased EGFR gene copy numbers. RESULTS: Seventeen patients had EGFR mutations, all of which were in lung adenocarcinomas. Radiographic response was observed in 16 of 17 (94.1%) patients harboring EGFR mutations, in contrast with 6 of 51 (12.6%) with wild-type EGFR (P < 0.0001). Probability of response increased significantly in never smokers, patients receiving a greater number of prior chemotherapy regimens, Asians, and younger patients. Median survival was not reached for patients with EGFR mutations and was 9.9 months for those with wild-type EGFR (P = 0.001). EGFR mutations tended to be associated with increased numbers of CA repeats and increased EGFR gene copy numbers but not with EGFR and caveolin-1 mRNA overexpression (P = not significant). CONCLUSIONS: The presence of EGFR mutations is a major determinant of gefitinib response, and targeting EGFR should be considered in preference to chemotherapy as first-line treatment in lung adenocarcinomas that have demonstrable EGFR mutations.

Relationship of Smoking with the CD4+ T cell count and Viral Load in Patients with the Human Immunodeficiency Virus in the HIV health care center at the Hospital Regional Universitario José María Cabral y Báez in the Dominican Republic: a Cross-sectional Descriptive Study / Relación entre tabaquismo, conteo de CD4+ y carga viral en pacientes con infección por Virus de Inmunodeficiencia Humana en el centro de atención para VIH del Hospital Regional Universitario José María Cabral y Báez de Republica Dominicana: estudio descriptivo transversal

Abstract Objective: To evaluate the relationship between tobacco use and viral load and CD4+ T cell count in HIV patients. Results: The research conducted was a descriptive study of 317 patients on highly active antiretroviral therapy (HAART), 18 years old and above, who attended the "Unidad de Atención Integral" (UAI) at the Hospital Regional Universitario José María Cabral y Báez, in Santiago, Dominican Republic. Of those 317 patients, 172 were included in the data analysis. It was found that a 77.3% of smokers had a CD4+ T cell count equal to or below 250 cells/mm3. 75% of smokers had a viral load equal to or greater than 400 copies/ml. In addition, 82.9% of nonsmokers presented with a viral load below 400 copies/ml. The smokers were more likely to have a viral load equal to or greater than 400 copies/ml (OR = 6.285, P < 0.001), in comparison with nonsmokers. Patients younger than 45 years old were more likely to have a viral load equal to or above 400 copies/ml compared to older patients (OR = 3.313, P = 0.024).

Resumen Objetivo: Evaluar la relación entre el consumo de tabaco, la carga viral y el recuento de linfocitos T CD4+ en pacientes con VIH. Resultados: La investigación fue realizada mediante un estudio descriptivo a 317 pacientes en terapia antirretroviral de alta actividad (TARGA), de 18 años o ma yores, que asistían a la Unidad de Atención Integral (UAI) del Hospital Regional Universitario José María Cabral y Báez, en Santiago, República Dominicana. De esos 317 pacientes, 172 se incluyeron en el análisis de datos. Se encontró que un 77,3% de los fumadores tenían un recuento de células T CD4 + igual o inferior a 250 células / mm3. El 75% de los fumadores tenían una carga viral igual o superior a 400 copias / ml. Además, el 82,9% de los no fumadores presentaba una carga viral inferior a 400 copias / ml. Los fumadores tenían más probabilidades de tener una carga viral igual o superior a 400 copias / ml (OR = 6.285, P <0.001), en comparación con los no fumadores. Los pacientes menores de 45 años tenían más probabilidades de tener una carga viral igual o superior a 400 copias / ml en comparación con los pacientes mayores (OR = 3,313, P = 0,024).

Lessons Learned from Twelve Years of Partnered Tobacco Cessation Research in the Dominican Republic.

Engaging partners for tobacco control within low and middle income countries (LMICs) at early stages of tobacco control presents both challenges and opportunities in the global effort to avert the one billion premature tobacco caused deaths projected for this century. The Dominican Republic (DR) is one such early stage country. The current paper reports on lessons learned from 12 years of partnered United States (US)-DR tobacco cessation research conducted through two NIH trials (Proyecto Doble T, PDT1 and 2). The projects began with a grassroots approach of working with interested communities to develop and test interventions for cessation and secondhand smoke reduction that could benefit the communities, while concurrently building local capacity and providing resources, data, and models of implementation that could be used to ripple upward to expand partnerships and tobacco intervention efforts nationally. Lessons learned are discussed in four key areas: partnering for research, logistical issues in setting up the research project, disseminating and national networking, and mentoring. Effectively addressing the global tobacco epidemic will require sustained focus on supporting LMIC infrastructures for tobacco control, drawing on lessons learned across partnered trials such as those reported here, to provide feasible and innovative approaches for addressing this modifiable public health crisis.