Spontaneous Remission of Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Report.

Spontaneous remissions (SRs) in blastic plasmacytoid dendritic cell neoplasms (BPDCNs) are infrequent, poorly documented, and transient. We report a 40-year-old man presenting with bycitopenia and soft tissue infection. The bone marrow exhibited 3% abnormal cells. Immunophenotyping of these cells revealed the antigens CD45+ (dim), CD34+, CD117+, CD123+ (bright), HLA-DR+ (bimodal), CD56+ (bright), CD33+, CD13+, CD2+, and CD22+ (dim) and the partial expression of the CD10+, CD36+, and CD7+ antigens. All other myeloid, monocytic, and lymphoid antigens were negative. Genetic studies showed a complex karyotype and mutations in the TP53R337C and KRASG12D genes. On hospital admission, the patient showed a subcutaneous nodule on the right hand and left lower limb. Flow cytometry multiparameter (FCM) analysis showed the presence of 29% abnormal cells with the previously described immunophenotype. The patient was diagnosed with BPDCN. The patient was treated with broad-spectrum antibiotics for soft tissue infection, which delayed therapy for BPDCN. No steroids or chemotherapeutic or hypomethylating agents were administered. His blood cell counts improved and skin lesions disappeared, until the patient relapsed five months after achieving spontaneous remission. About 60% of abnormal cells were identified. No changes in immunophenotype or the results of genetic studies were observed. The patient underwent a HyperCVAD chemotherapy regimen for six cycles. Consolidation therapy was performed via allogeneic bone marrow transplantation with an HLA-unrelated donor. One year after the bone marrow transplant, the patient died due to the progression of his underlying disease, coinciding with a respiratory infection caused by SARS-CoV-2. In the available literature, SRs are often linked to infections or other stimulators of the immune system, suggesting that powerful immune activation could play a role in controlling the leukemic clone. Nevertheless, the underlying mechanism of this phenomenon is not clearly understood. We hypothesize that the immune system would force the leukemic stem cell (LSC) to undergo a state of quiescence. This loss of replication causes the LSC progeny to die off, resulting in the SR of BPDCN.

Health workers cohort study: methods and study design / Cohorte de trabajadores de la salud: métodos y diseño del estudio

Abstract: Objective: To examine different health outcomes that are associated with specific lifestyle and genetic factors. Materials and methods: From March 2004 to April 2006, a sample of employees from three different health and academic institutions, as well as their family members, were enrolled in the study after providing informed consent. At baseline and follow-up (2010-2013), participants completed a self-administered questionnaire, a physical examination, and provided blood samples. Results: A total of 10 729 participants aged 6 to 94 years were recruited at baseline. Of these, 70% were females, and 50% were from the Mexican Social Security Institute. Nearly 42% of the adults in the sample were overweight, while 20% were obese. Conclusion: Our study can offer new insights into disease mechanisms and prevention through the analysis of risk factor information in a large sample of Mexicans.

Resumen: Objetivo: Examinar diferentes desenlaces en salud y su asociación con factores genéticos y del estilo de vida. Material y métodos: De marzo de 2004 a abril de 2006, una muestra de empleados de tres diferentes instituciones de salud y académicas, así como miembros de sus familias, fueron enrolados en el estudio, previa firma de consentimiento informado. Durante la medición basal y el seguimiento (2010-2013) los participantes completaron un cuestionario autoaplicado, exámenes físicos y proporcionaron muestras sanguíneas. Resultados: Fueron incluidos participantes (10 729) de entre 6 y 94 años en la medición basal. De estos, 70% fueron mujeres y 50% del Instituto Mexicano del Seguro Social. Aproximadamente 42% de los adultos tuvieron sobrepeso y 20% obesidad. Conclusión: Este estudio puede ofrecer conocimientos sobre los mecanismos de la enfermedad a través del análisis de factores de riesgo en una muestra de mexicanos.

Health workers cohort study: methods and study design.

OBJECTIVE:: To examine different health outcomes that are associated with specific lifestyle and genetic factors. MATERIALS AND METHODS:: From March 2004 to April 2006, a sample of employees from three different health and academic institutions, as well as their family members, were enrolled in the study after providing informed consent. At baseline and follow-up (2010-2013), participants completed a self-administered questionnaire, a physical examination, and provided blood samples. RESULTS:: A total of 10 729 participants aged 6 to 94 years were recruited at baseline. Of these, 70% were females, and 50% were from the Mexican Social Security Institute. Nearly 42% of the adults in the sample were overweight, while 20% were obese. CONCLUSION:: Our study can offer new insights into disease mechanisms and prevention through the analysis of risk factor information in a large sample of Mexicans.

Differences in cerebrospinal fluid inflammatory cell reaction of patients with leptomeningeal involvement by lymphoma and carcinoma.

Dissemination of neoplastic cells into the cerebrospinal fluid (CSF) and leptomeninges is a devastating complication in patients with epithelial cell neoplasia (leptomeningeal carcinomatosis [LC]) and lymphomas (lymphomatous meningitis [LyM]). Information about the surrounding inflammatory cell populations is scarce. In this study, flow cytometry immunophenotyping was used to describe the distribution of the main leukocyte populations in the CSF of 83 patients diagnosed with neoplastic meningitis (LC, n = 65; LyM, n = 18). These data were compared with those obtained in the CSF from 55 patients diagnosed with the same groups of neoplasia without meningeal involvement (solid tumors, n = 36; high-grade lymphoma, n = 19). Median (interquartile) rates of lymphocytes, monocytes, and polymorphonuclear (PMN) cells were 59.7% (range, 35-76.6%), 24% (range, 16-53%), and 1.5% (range, 0-7.6%) in LC, respectively, and 98.5% (range, 70.8-100%), 1.5% (range, 0-29.3%), and 0% in LyM, respectively (P < 0.001). No difference was observed between patients with breast adenocarcinoma (n = 30) and lung adenocarcinoma (n = 21), nor with different rates of malignant CSF involvement. Patients with lymphoma (with or without LyM) had a similar CSF leukocyte distribution, but cancer patients with LC and without LC had a distinctive PMN cell rate (P = 0.002). These data show that CSF samples from patients with LC have a greater number of inflammatory cells and a different leukocyte distribution than seen in the CSF from patients with LyM. Description of PMN cells is a distinctive parameter of patients with LC, compared with the CSF from patients with LyM and patients with cancer but without LC.

Association between dietary patterns and insulin resistance in Mexican children and adolescents.

BACKGROUND/OBJECTIVE: Insulin resistance (IR) is a metabolic disorder that is increasing worldwide and has been associated with several negative health outcomes. The aim of this study was to evaluate the relationship between different dietary patterns and IR among Mexican children and adolescents. METHODS: We performed a cross-sectional analysis on baseline data from Mexican children and adolescents aged 7­18 years participating in the Health Workers Cohort Study. We included 916 children and adolescents of both sexes. Fasting serum glucose and insulin levels were determined by standardized methods. We defined IR using the homeostasis model assessment (HOMA) as ≥3.5. Factor analysis was used to identify dietary patterns. The associations of interest, those between IR and dietary patterns, were analyzed with multiple logistic regression models. RESULTS: IR prevalence was 20.3% among girls and boys aged 7­18 years, for whom the prevalence of overweight and obesity was 29.7%. We identified 3 major dietary patterns in this group: 'Western', 'prudent' and 'high protein/fat'. For the purposes of this analysis we compared the upper versus the lower quintile of each dietary pattern. Independently of other covariates, participants in the highest quintile of the Western pattern had 92% greater odds of IR (OR 1.92, 95% CI: 1.08­3.43) compared with those in the lowest quintile. CONCLUSIONS: These findings support the hypothesis that high carbohydrate diets like our Western dietary pattern may increase IR in young people. This result emphasizes the importance of preventive nutrition interventions geared toward Mexican children and adolescents.

Role of flow cytometry immunophenotyping in the diagnosis of leptomeningeal carcinomatosis.

PURPOSE: To explore the contribution of flow cytometry immunophenotyping (FCI) in detecting leptomeningeal disease in patients with solid tumors. EXPERIMENTAL DESIGN: Cerebrospinal fluid (CSF) samples from 78 patients who received a diagnosis of epithelial-cell solid tumors and had clinical data suggestive of leptomeningeal carcinomatosis (LC) were studied. A novel FCI protocol was used to identify cells expressing the epithelial cell antigen EpCAM and their DNA content. Accompanying inflammatory cells were also described. FCI results (positive or negative for malignancy) were compared with those from CSF cytology and with the diagnosis established by the clinicians: patients with LC (n = 49), without LC (n = 26), and undetermined (n = 3). RESULTS: FCI described a wide range of EpCAM-positive cells with a hyperdiploid DNA content in the CSF of patients with LC. Compared with cytology, FCI showed higher sensitivity (75.5 vs 65.3) and negative predictive value (67.6 vs 60.5), and similar specificity (96.1 vs 100) and positive predictive value (97.4 vs 100). Concordance between cytology and FCI was high (Kp = 0.83), although misdiagnosis of LC did not show differences between evaluating the CSF with 1 or 2 techniques (P = .06). Receiver-operator characteristic curve analyses showed that lymphocytes and monocytes had a different distribution between patients with and without LC. CONCLUSION: FCI seems to be a promising new tool for improving the diagnostic examination of patients with suspicion of LC. Detection of epithelial cells with a higher DNA content is highly specific of LC, but evaluation of the nonepithelial cell compartment of the CSF might also be useful for supporting this diagnosis.

Dietary patterns are associated with different indexes of adiposity and obesity in an urban Mexican population.

Our objective was to evaluate the relationships between dietary patterns and obesity, abdominal obesity, and high body fat proportion (measured by dual-energy X-ray absorptiometry; >25% in men and >35% in women) in an urban Mexican population. We conducted a cross-sectional analysis with the baseline data from 6070 men and women aged 20-70 y participating in the Health Workers Cohort Study, including information on participants' socio-demographic status and physical activity collected via self-administered questionnaires. Dietary intake was evaluated using a 116-item FFQ. Anthropometric measures were obtained using standardized procedures. We used factor analysis to identify 3 major dietary patterns: prudent, Westernized, and high animal protein/fat. We found that participants in the highest quintile of the prudent pattern were less likely to have high-body fat proportion (OR, 0.82; 95% CI: 0.70-0.98) and that participants in the highest quintile of the Westernized pattern had greater odds for obesity (OR, 1.46; 95% CI: 1.23-1.73), abdominal obesity (OR, 1.64; 95% CI: 1.37-1.96), and high-body fat proportion (OR, 1.17; 95% CI: 1.01-1.35). Additionally, participants in the upper quintile of the high-animal protein/-fat pattern had greater odds of being obese (OR, 1.23; 95% CI: 1.06-1.42). These results indicate that the dietary patterns of Mexican adults are associated with different levels of adiposity and obesity. Further prospective studies are required to confirm these associations.

Dietary patterns are associated with metabolic syndrome in an urban Mexican population.

The role that diet plays in the origin of metabolic syndrome (MetS) is not completely understood. Certain foods and nutrients have been established as dietary risk factors for MetS. However, the dietary patterns associated with MetS risk have been minimally studied with factor analysis. Our objective in this study was to use exploratory factor analysis to examine whether particular dietary patterns are related to risk of MetS in Mexican adults. We characterized the dietary patterns among 5240 men and women aged 20-70 y in the Health Workers Cohort Study. Information on participants' sociodemographic conditions and physical activity was collected via self-administered questionnaires. We also obtained anthropometric and clinical measurements and fasting blood samples for biochemical analyses. In a cross-sectional analysis, we examined dietary patterns in relation to MetS, defined using criteria from the Adult Treatment Panel III. Factor analysis revealed 3 major dietary patterns: prudent, Western, and high protein/fat. The prevalence of MetS was 26.6%. After adjustment for potential confounders, compared with participants in the lowest tertile of the Western pattern, those in the highest tertile had higher odds ratios (OR) for high fasting glucose (OR, 1.67; 95% CI: 1.36-2.06), low serum HDL cholesterol (OR, 1.55; 95% CI: 1.31-1.83), and MetS (OR, 1.56; 95% CI, 1.31-1.88). However, we found no significant associations between other patterns and MetS. In summary, a diet high in soft drinks, refined grains, corn tortillas, pastries, seafood, and whole grains was associated with MetS risk. This result emphasizes the importance of preventive nutrition interventions.

Dietary glycemic index, dietary glycemic load, blood lipids, and coronary heart disease.

Objective. To examine the associations of dietary glycemic index (GI) and dietary glycemic load (GL) with blood lipid concentrations and coronary heart disease (CHD) in nondiabetic participants in the Health Worker Cohort Study (HWCS). Materials and Methods. A cross-sectional analysis was performed, using data from adults who participated in the HWCS baseline assessment. We collected information on participants' socio-demographic conditions, dietary patterns and physical activity via self-administered questionnaires. Dietary GI and dietary GL were measured using a validated food frequency questionnaire. Anthropometric and clinical measurements were assessed with standardized procedures. CHD risk was estimated according to the sex-specific Framingham prediction algorithms. Results. IIn the 5,830 individuals aged 20 to 70 who were evaluated, dietary GI and GL were significantly associated with HDL-C, LDL-C, LDL-C/HDL-C ratio, and triglycerides serum levels. Subjects with high dietary GI have a relative risk of 1.56 (CI 95%; 1.13-2.14), and those with high dietary GL have a relative risk of 2.64 (CI 95%; 1.15-6.58) of having an elevated CHD risk than those who had low dietary GI and GL. Conclusions. Our results suggest that high dietary GI and dietary GL could have an unfavorable effect on serum lipid levels, which are in turn associated with a higher CHD risk.

Immunophenotype in chronic myelomonocytic leukemia: is it closer to myelodysplastic syndromes or to myeloproliferative disorders?

Chronic myelomonocytic leukemia (CMML) is a heterogeneous disease balanced between myelodysplastic syndromes (MDS) and myeloproliferative disorders (MPD). We used flow cytometry to describe and compare the immunophenotypic profile of 20 patients with CMML, 38 patients with MDS, and 20 patients with MPD. CMML and MDS only showed statistically significant differences (P<0.05) in CD56 monocyte expression. CMML and MPD showed significant differences in CD45 myeloid distribution, myeloid antigenic profile, CD56 and CD2 monocyte expression, and B-cell development. These data support the classic concept of CMML as part of MDS diseases and encourage including immunophenotyping among the studies to be performed in these diseases.

Body mass index and the prevalence of metabolic syndrome among children and adolescents in two Mexican populations.

PURPOSE: To report the prevalence of metabolic syndrome (MS) among children and adolescents living in central Mexico, and its association with body mass index (BMI). METHODS: In a sample of 1366 subjects from 7 to 24-years-old, a self-administered questionnaire was used to determined demographic characteristics. The definition of pediatric MS was determined using analogous criteria to Adult Treatment Panel III (ATPIII) as > or = 3 of the following: concentration of triglycerides > or = 100 mg/dL, HDL cholesterol < 45 mg/dL for males and < 50 mg/dL for females, waist circumference > or = 75th percentile (sex specific), glucose concentration > or = 110 to < 126 mg/dL, and systolic or diastolic blood pressure > or = 90th percentile (age, height, and sex specific). RESULTS: Most of the sample was in the 10-14- (32.4%) and the 15-19-year (35.4%) age groups, mostly females (57%), and 31% of this young sample was overweight (mean BMI = 21.6 kg/m2). About 1 in every 5 participants had full criteria for MS (19.2%, 95% confidence interval [CI]: 16.4-22.1 among females, and 20.2%, 95% CI: 17.1-23.7 among males), and only 1 in every 10 was free of any MS component. The most common component was a low HDL level, observed in 85.4% of the sample. Unfavorable fat distribution, as indicated by a large waist circumference, was present in 27.9% of the sample. About 66% of those 10-14-year-olds with a large BMI were positive for MS. CONCLUSIONS: MS and overweight are major problems for youth in Mexico. Immediate and comprehensive actions at home and schools are needed if Mexico wants to avoid the heavy burden that this disorder will have for its population in the near future.

Virus-specific effector CD4+ T-cell responses in hemodialysis patients with hepatitis C virus infection.

Patients with chronic renal failure undergoing hemodialysis who are infected with hepatitis C virus (HCV) may test consistently anti-HCV negative. Because CD4(+) T-cells provide help for antibody production virus-specific effector CD4(+) T-cell responses were investigated in relation to anti-HCV positivity in 15 hemodialysis patients grouped according to HCV antibody and viremia. CD4(+) T-cell reactivity was studied in peripheral blood mononuclear cells by standard lymphocyte proliferation assay and phenotypic/functional characterization (cell-surface staining/cytokine secretion) by flow cytometry. HCV-specific CD4(+) T-cell proliferation in viremic hemodialysis patients was weak or absent independently of their anti-HCV status. Virus-specific CD4(+) T-cells displayed a memory phenotype and showed low to undetectable capacity to secrete effector interferon (IFN)-gamma. Impaired activation-induced cytokine secretion appeared to be Th1 (IFN-gamma) but not Th2 (interleukin-4)-directed and was virus-specific as cytomegalovirus responses were preserved. The frequency ex vivo of CD3(+)CD4(+)IFN-gamma(+) T-cells was independent of the HCV antibody status and comparable between viremic (range: 0.08-1.54%) or non-viremic (0.11-3.2%) hemodialysis patients and healthy donors (0.13-1.10%; P = 0.58). The numbers of CD3(+)CD4(+)IFN-gamma(+) T-cells augmented slightly (P = 0.047) in HCV-infected hemodialysis patients but markedly in only one (greater than ninefold) after HCV stimulation. In conclusion, hemodialysis patients show limited HCV-specific effector CD4(+) Th1-cell responses which nonetheless seem unrelated to the anti-HCV status and are not more impaired due to the ongoing hemodialysis.

Flow cytometric analysis of cerebrospinal fluid samples and its usefulness in routine clinical practice.

Low volume and few cells have hampered the use of flow cytometry for studying cerebrospinal fluid (CSF) in routine clinical practice, although information about the cellular phenotypes present in this type of sample is of great value in many diseases. We developed a novel flow cytometric strategy capable of identifying total CSF T lymphocytes and the CD4+ subset, even in CSF samples with as few as 1 leukocyte per 3 microL of sample. We also showed that identification of CD8+ T cells could be achieved in most samples, while B lymphocytes are detectable only in samples with more than 5 cells per microliter. These findings demonstrate the reliability of this method to improve the diagnostic accuracy of classic cytologic studies in many neurologic disorders.

Role of antiretroviral regimes in HIV-1 patients in reducing immune activation.

We assessed whether antiretroviral regimes are able to diminish apoptosis and markers of lymphocyte activation and restore lymphocyte proliferation. T-cell subset, spontaneous and induced apoptosis, CD95 and soluble Fas antigen and cell proliferation were analysed in 41 human immunodeficiency virus type 1-positive patients. Twenty-five were in asymptomatic stage A and 16 were in stage B/C. Thirty-five received antiretroviral treatment: 18 received two inhibitors of reverse transcriptase and one protease inhibitor and 17 received three inhibitors of reverse transcriptase. Six patients did not receive treatment, for different reasons, but continued to participate in the study. Studies were performed at baseline, 3, 6 and 12 months. Levels of CD4 increased slightly until 6 months of antiretroviral treatment, as a whole, in all the patients treated. Naïve CD4 lymphocytes, as well as memory CD4 lymphocytes, remained constant. Spontaneous apoptosis of lymphocytes, after 72 hr of culture, decreased in all patients treated, but to a much smaller extent than phytohaemagglutinin-induced apoptosis. In both groups treated, levels of soluble Fas decreased until 6 months of treatment and then increased again. Lymphocyte proliferation reached normal levels after 1 year of treatment. In patients without treatment CD4 cells decreased slowly and no modification in activation markers was found. Antiretroviral regimes decrease immune activation as well as viral load and this deactivation restores lymphocyte proliferation.

Features of the CD4+ T-cell response in liver and peripheral blood of hepatitis C virus-infected patients with persistently normal and abnormal alanine aminotransferase levels.

BACKGROUND/AIMS: The liver is the primary site of hepatitis C virus (HCV) replication; intrahepatic T-cell responses may influence liver disease severity. METHODS: HCV-specific CD4(+) T-cell reactivity was investigated ex vivo in paired liver tissue and peripheral blood from 42 chronic HCV patients. RESULTS: The frequencies with which HCV-specific HLA class-II-restricted CD4(+) T-cell proliferation were observed were 29% in liver and 36% in peripheral blood. Among responses, non-structural-3 protein (NS3)-specific T-cell proliferation was dominant but non-exclusive and did rarely occur concurrently in liver infiltrate and peripheral blood suggesting liver compartmentalization of a CD4(+) T-cells population. Compared with 24 patients with abnormal ALT levels, 18 HCV carriers with persistently normal ALT levels had similar serum and liver viral loads but showed: (i) a low-activity grade and stage chronic hepatitis (P<0.001); (ii) less intrahepatic CD4(+) T-lymphocytes (P<0.01); (iii) less frequent intrahepatic (17 vs. 33%) and peripheral (17 vs. 38%) NS3-specific CD4(+) T-cell proliferation; (iv) less often in vitro T-helper (Th)1 (interferon-gamma) cytokine production (2 vs. 18%; P<0.001). CONCLUSIONS: Our data show a low frequency of intrahepatic HCV-specific HLA class-II-restricted CD4(+) Th1 responses in patients with chronic HCV. However, these Th1 responses are detected more often in those patients with overt clinical and histological disease.