Non-alcoholic fatty liver disease and thrombocytopenia IV: its association with granulocytopenia

ABSTRACT Introduction: We have previously shown that some patients present thrombocytopenia (less than 100 × 109/L platelets) in non-alcoholic fatty liver disease (NAFLD). To further explore the nature of this association, we have now analyzed the association of thrombocytopenia with neutropenia (less than 0.5 × 109/L granulocytes) in NAFLD. Material and methods: Persons with NAFLD were prospectively accrued in the study after February 2018. The presence of NAFLD was defined by both serologic determinations (Fibromax ®) and liver transient elastography (TE/Fibroscan ®). Results: In 123 consecutive patients with NAFLD without cirrhosis, thrombocytopenia was identified in 20 (16%), whereas neutropenia was identified in 9 (7%). In the subset of 20 patients with NAFLD and thrombocytopenia, granulocytopenia was identified in 5 (25%), whereas in the subset of 9 patients with granulocytopenia, thrombocytopenia was identified in 5 (55%). We found a significant association between thrombocytopenia and both leukopenia and granulocytopenia (OR 8.25, 95% CI 1.9-34.2, p = 0.004). Conclusions: Both thrombocytopenia and neutropenia were identified in persons with NAFLD and, as there is a significant relationship between these two variables, we speculate that this finding may support the possibility of hypersplenism being involved in the cytopenias found in NAFLD without cirrhosis.

Familias de médicos en la Academia Nacional de Medicina de México / Families of doctors at Academia Nacional de Medicina de México

Resumen Introducción: La decisión de involucrarse en el estudio y la práctica de la medicina no es fácil. Dentro del ambiente científico, alcanzar el éxito tanto profesional como personal requiere de una disciplina estricta en donde el esfuerzo se vuelve parte esencial de la vida diaria, además, el tener el apoyo familiar se vuelve un pilar para no perder la ilusión ante las distintas adversidades que se presentan en la formación médica. Objetivo: Identificar a las familias donde mínimo dos miembros pertenecen a la Academia Nacional de Medicina. Métodos: Se llevó a cabo un estudio transversal para analizar las familias de médicos mexicanos en las que por lo menos dos miembros, consanguíneos o políticos, han sido o son miembros de la Academia Nacional de Medicina de México por medio de la consulta del Directorio de la Academia Nacional de Medicina del año 2017 y el contacto de manera personal con los distintos académicos. Resultados: Se recolectó información de 45 familias pertenecientes a la Academia Nacional de Medicina de México. Conclusiones: A partir de este estudio es posible evidenciar la gran influencia que emiten algunos médicos en su entorno familiar, que hace que el estudio de la medicina sea atractivo como proyecto de vida.

Abstract Introduction: The decision to get involved in the study and practice of medicine is not easy. Within the scientific environment, achieving both professional and personal success requires a strict discipline, where effort becomes an essential part of daily life; in addition, having family support becomes crucial in order for not to lose hope when confronting the different adversities that arise during medical training. Objective: To identify members where at least two members belong to the Academia Nacional de Medicina de México" (ANMM). Methods: A cross-sectional study was carried out to identify families of Mexican doctors where at least two members, consanguineous or in-laws, have been or are ANMM members of the through a review of 2017 ANMM Directory personal contact with the different academics. Results: Information on 45 families belonging to the ANMM was collected. Conclusions: From this study, it is possible to show the great influence that some doctors have in their family environment, wich makes the study of medicine attractive as a life project.

Non-alcoholic fatty liver disease and thrombocytopenia IV: its association with granulocytopenia.

INTRODUCTION: We have previously shown that some patients present thrombocytopenia (less than 100 × 109/L platelets) in non-alcoholic fatty liver disease (NAFLD). To further explore the nature of this association, we have now analyzed the association of thrombocytopenia with neutropenia (less than 0.5 × 109/L granulocytes) in NAFLD. MATERIAL AND METHODS: Persons with NAFLD were prospectively accrued in the study after February 2018. The presence of NAFLD was defined by both serologic determinations (Fibromax ®) and liver transient elastography (TE/Fibroscan ®). RESULTS: In 123 consecutive patients with NAFLD without cirrhosis, thrombocytopenia was identified in 20 (16%), whereas neutropenia was identified in 9 (7%). In the subset of 20 patients with NAFLD and thrombocytopenia, granulocytopenia was identified in 5 (25%), whereas in the subset of 9 patients with granulocytopenia, thrombocytopenia was identified in 5 (55%). We found a significant association between thrombocytopenia and both leukopenia and granulocytopenia (OR 8.25, 95% CI 1.9-34.2, p = 0.004). CONCLUSIONS: Both thrombocytopenia and neutropenia were identified in persons with NAFLD and, as there is a significant relationship between these two variables, we speculate that this finding may support the possibility of hypersplenism being involved in the cytopenias found in NAFLD without cirrhosis.

Long term survival in multiple myeloma: a single institution experience in underprivileged circumstances.

There is data suggesting that the clinical behavior of multiple myeloma (MM) may be different in Latin Americans than in Caucasian or African-Americans, consistent with a less aggressive course of MM in Latinos. We analyzed the overall survival (OS) of 139 persons with MM in a single institution in México, as well the variables which were associated with long-term OS. Of all patients, the median OS was 11 years whereas the 5-year and 10-year OS were 75% and 55% respectively. The analysis of variables showed that the variable related with five-year survival was having hematopoietic stem cell transplantation (HSCT), whereas the variables related with 10-year survival were HSCT, age at diagnosis (patients younger than 50 survived longer), light chain type (kappa survived longer) and ISS stage (stage I patients survived longer). The only variable associated with both 5 and 10-year survival was HSCT. A plateau in the OS was reached after 10 years, both in grafted and non-grafted patients. We have confirmed the critical role of HSCT in the prognosis of persons with MM, independent of the induction treatment or the maintenance post-transplant, and we have identified a better prognosis in this cohort, as compared with African-Americans or Caucasians, since the proportion of long-term survivors in our group is seemingly better than those in other populations.

Long-term results of the treatment of Hodgkin's lymphoma in a resource-constrained setting: Real-world data from a single center.

BACKGROUND: The outcomes of Hodgkin´s lymphoma (HL) in México have not been widely reported. Simplified and affordable treatments have been adopted in middle-income countries. AIM: The aim was to evaluate long-used therapies for HL in México in a long-term basis. METHODS: In a 34-year time period, 88 patients with HL were treated at a single institution in México. Patients were treated with adriamycin bleomycin vinblastine and dacarbazine (ABVD) or mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). Relapsed or refractory patients were given ifosfamide, carboplatin, and etoposide (ICE) followed by autologous or allogeneic stem cell transplants. RESULTS: Thirty-seven women and 51 men were included; the median age was 29 years. Patients were followed for a mean of 128 mo. The 310-mo overall survival (OS) was 83% for patients treated with MOPP and 88% for those treated with ABVD. The OS of patients who received autologous stem cell transplantation was 76% (330 mo) vs 93% (402 mo) in those who did not. CONCLUSION: HL may be less aggressive in Mexican population than in Caucasians. Combined chemotherapy renders acceptable results, regardless of clinical stage.

Mantle cell lymphoma may have a different clinical course in Mexican Mestizos: Real-world data from a single center

ABSTRACT Background: The biology of some hematological diseases varies among different populations. No previous studies have evaluated the clinical behavior of mantle cell lymphoma (MCL) in México. Objective and Methods: This is a retrospective review of MCL cases seen in Mexico from January 2003 to June 2020. A total of 12 cases were identified. Results: There were nine males and three females; median age was 56 years. Eight patients had a high MCL international prognostic index score, one was intermediate, and three were low. Five patients had circulating malignant monoclonal cells. Initial treatment included rituximab, cyclophosphamide, daunorubicin, vincristine, and prednisone (R-CHOP) and CHOP. Subsequent treatment included hematopoietic stem cell transplantation in five patients; two were given maintenance therapy. Splenectomy was done in four patients. Median overall survival (OS) for all the patients has not been reached and exceeds 162 mos: OS at 162 mos was 56%. Achieving a complete remission (CR) after the first treatment was a significant prognostic factor, with a median OS exceeding 141 mos in patients achieving CR, and 16 mos among those not achieving CR (p = 0.0006). Conclusion: Some of MCL patients in Mexico have an indolent clinical course, particularly patients who achieve a CR to initial treatment and who undergo splenectomy.

The 1,000th Transplant for Multiple Sclerosis and Other Autoimmune Disorders at the HSCT-México Program: A Myriad of Experiences and Knowledge.

After gaining experience conducting both auto and allografts in persons with hematological diseases in the HSCT programs in Puebla and Monterrey, México, this study outlines subsequent program autografting patients with autoimmune conditions. The first transplant in multiple sclerosis was conducted in Puebla on July 5, 2006. From 2015 we increased activity autografting persons with autoimmune conditions in the two campuses of the HSCT-México program: Puebla and Monterrey. By December 6, 2020, patient number 1,000 in the program was autografted. In our experience, a significant reduction in the expanded disability status scale score was achieved in all of the three phenotypes of the disease (from a median of 5.1 to 4.5 points), whereas the response rate (defined as a decrease of at least 0.5 of EDSS score regardless of baseline EDSS, or unchanged EDSS) was 83, 78, and 73% after 12 months in the relapsing-remitting, primary-progressive and secondary-progressive forms of multiple sclerosis, respectively. In addition to analyzing the viability, safety, and efficacy of our method, this study contributes new knowledge to the field of both stem cell transplantation and multiple sclerosis.

Mantle cell lymphoma may have a different clinical course in Mexican Mestizos: Real-world data from a single center.

BACKGROUND: The biology of some hematological diseases varies among different populations. No previous studies have evaluated the clinical behavior of mantle cell lymphoma (MCL) in México. OBJECTIVE AND METHODS: This is a retrospective review of MCL cases seen in Mexico from January 2003 to June 2020. A total of 12 cases were identified. RESULTS: There were nine males and three females; median age was 56 years. Eight patients had a high MCL international prognostic index score, one was intermediate, and three were low. Five patients had circulating malignant monoclonal cells. Initial treatment included rituximab, cyclophosphamide, daunorubicin, vincristine, and prednisone (R-CHOP) and CHOP. Subsequent treatment included hematopoietic stem cell transplantation in five patients; two were given maintenance therapy. Splenectomy was done in four patients. Median overall survival (OS) for all the patients has not been reached and exceeds 162 mos: OS at 162 mos was 56%. Achieving a complete remission (CR) after the first treatment was a significant prognostic factor, with a median OS exceeding 141 mos in patients achieving CR, and 16 mos among those not achieving CR (p = 0.0006). CONCLUSION: Some of MCL patients in Mexico have an indolent clinical course, particularly patients who achieve a CR to initial treatment and who undergo splenectomy.

Infusion of convalescent plasma is associated with clinical improvement in critically ill patients with Covid-19: a pilot study

ABSTRACT Background: The ideal treatment of coronavirus disease (COVID)-19 has yet to be defined, but convalescent plasma (CoPla) has been successfully employed. Objective: The objective of the study was to study the safety and outcomes of the administration of CoPla to individuals with severe COVID-19 in an academic medical center. Methods: Ten patients were prospectively treated with plasma from COVID-19 convalescent donors. Results: Over 8 days, the sequential organ failure assessment score dropped significantly in all patients, from 3 to 1.5 (p = 0.014); the Kirby index (PaO2/FiO2) score increased from 124 to 255, (p < 0.0001), body temperature decreased significantly from 38.1 to 36.9°C (p = 0.0058), and ferritin levels also dropped significantly from 1736.6 to 1061.8 ng/ml (p = 0.0001). Chest X-rays improved in 7/10 cases and in 6/10, computerized tomography scans also revealed improvement of the lung injury. Decreases in C-reactive protein and D-dimer levels were also observed. Three of five patients on mechanical ventilation support could be extubated, nine were transferred to conventional hospital floors, and six were sent home; two patients died. The administration of CoPla had no side effects and the 24-day overall survival was 77%. Conclusions: Although other treatments were also administered to the patients and as a result data are difficult to interpret, it seems that the addition of CoPla improved pulmonary function.

Up to half of patients diagnosed with chronic lymphocytic leukemia in México may not require treatment.

Introduction: Although therapeutic choices for patients with chronic lymphocytic leukemia (CLL) were once limited, treatment of this disease has vastly improved in the last decades.Patients and methods: Consecutive CLL patients diagnosed in a single institution were analyzed. Treatment was withheld in persons with CLL Rai stage 0 or 1, until progression and in persons with stages 2-4, with a negative expression of ZAP-70 until progression. Between 1983 and 1991, patients were give chlorambucil and prednisone (CP); after 1991 fludarabine and cyclophosphamide (FC) and after 1998, rituximab and FC (FCR).Results: 98 patients with CLL were identified; 49 were followed for >3 months. 21 persons (43%) did not require treatment nor progressed; 14 received CP, 6 FC, 7 FCR and one rituximab. Median overall survival (OS) has not been reached, being above 247 months; median OS for patients given CP was 115 months, for FC above 132 months and for FCR above 136 months (p > 0.5).Conclusion: CLL seems to be less aggressive in Mexican mestizos than in Caucasians; 43% of patients do not need treatment at all.

Treatment of Persons with Multiple Myeloma in Underprivileged Circumstances: Real-World Data from a Single Institution.

BACKGROUND: The treatment of patients with multiple myeloma (MM) has evolved in recent years, and the disease-associated prognosis has improved substantially. This improvement has been driven largely by the approval of novel agents, many of which are expensive and not universally available. Less expensive but effective approaches would be of value globally. PATIENTS AND METHODS: All consecutive MM patients diagnosed in the Centro de Hematología y Medicina Interna de Puebla after 1993 were included in this study. Patients were given oral thalidomide (100 mg/day), oral dexamethasone (36-40 mg/week), and aspirin 100 mg/day. Bor-tezomib (1.75 mg s.c. every week) was administered to those who could afford it. After 4-6 weeks of treatment, patients were offered an outpatient-based hematopoietic cell transplant (HCT). After the recovery of granulocytes following HCT, patients continued indefinitely on thalidomide; those who failed to tolerate thalidomide were switched to lenalidomide (25 mg/day). RESULTS: The median overall survival (OS) for all patients has not been reached and is >157 months. Median follow-up of the patients lasted 14 months (range 1.3-157). The median OS of patients with and without HCT was similar. The response rate (complete remission or very good partial remission) was 72% for those given thalidomide plus dexamethasone versus 88% for those given bortezomib, thalidomide, and dexamethasone before HCT, but OS was not different. As post-HCT maintenance, 37 patients received thalidomide; 26 of those (70%) could be maintained indefinitely on thalidomide, whereas 11 were switched to lenalidomide after a median of 7 months; median OS of patients maintained on thalidomide or lenalidomide after HCT was not different. CONCLUSION: In this series, a regimen incorporating low-cost novel agents and outpatient HCT was associated with excellent long-term survival in the treatment of MM patients. This approach may be a model for MM treatment in underprivileged circumstances.

Nonalcoholic Fatty Liver Disease and Thrombocytopenia III: Its Association With Insulin Resistance.

Thrombocytopenia (less than 100 × 109/L platelets) presents in around one quarter of patients with nonalcoholic fatty liver disease (NAFLD), the hepatic component of insulin resistance (IR). It is unknown whether IR, by itself, associates with thrombocytopenia. Persons with NAFLD and/or IR were prospectively accrued in the study after February 2018. Insulin resistance was defined by assessing α hydroxybutyrate, lynoleoyl glycerolphosphocoline, oleic acid, and insulin (Quantose IR), whereas the presence of NAFLD was defined by serologic determinations (Fibromax) and liver transient elastography (Fibroscan). In 78 patients with NAFLD, thrombocytopenia was identified in 22 (28%), whereas in 19 persons with IR, 14 (73%) were found to have NAFLD. In persons with IR + NAFLD, thrombocytopenia presented in 9 (64%). In the subset of patients with IR, the prevalence of thrombocytopenia was 52%. There was only 1 patient with IR/without NAFLD who displayed thrombocytopenia. Significant statistical association between NAFLD and thrombocytopenia was found (odds ratio [OR]: = 13, confidence interval [CI]: 1.5-162, P = .05), whereas there was no association between IR and thrombocytopenia (OR = 0.38, CI: 0.06-2.3, P = .61). Insulin resistance, by itself, was not found to be associated with diminished platelet counts. The presence of NAFLD, one of the consequences of IR, seems to be required to lead into thrombocytopenia.

Primary Thrombophilia in Mexico XIII: Localization of the Thrombotic Events in Mexican Mestizos With the Sticky Platelet Syndrome.

The sticky platelet syndrome (SPS) is a common cause of both arterial and venous thrombosis, being a dominant autosomal disease with qualitative platelet alterations and familial occurrence. It is characterized by platelet hyperreactivity with increased platelet aggregability in response to low concentrations of platelet agonists: epinephrine, adenosine diphosphate, or both. The clinical manifestations involve venous or arterial thrombosis, recurrent pregnancy loss, and fetal growth retardation. To analyze the localization of the thrombotic episodes in a cohort of Mexican mestizo patients with SPS. Between 1992 and 2016, 86 Mexican mestizo patients with SPS as the single thrombophilic condition were prospectively identified; all of them had a history of thrombosis. There were 15 males and 71 females. The thrombotic episodes were arterial in 26 cases and venous in 60 (70%). Arterial thrombosis was mainly pulmonary thromboembolism, whereas venous thromboses were identified most frequently in the lower limbs. Mexican mestizo population with SPS is mainly female; the type I of the condition is the most frequent; both arterial and venous thrombosis can occur, and they are mainly pulmonary embolism and lower limbs venous thrombosis, respectively.

A Feasibility Study of the Full Outpatient Conduction of Hematopoietic Transplants in Persons with Multiple Sclerosis Employing Autologous Non-Cryopreserved Peripheral Blood Stem Cells.

BACKGROUND: With the goal of achieving immune system reset, autologous hematopoietic stem cell transplantations have been performed in patients with multiple sclerosis (MS). MATERIAL AND METHODS: Two hundred and eighty-six consecutive patients with MS were autografted in a single center using non-frozen peripheral blood stem cells (PBSCs), on an outpatient basis and conditioning with cyclophosphamide and rituximab. The protocol was registered in ClinicalTrials.gov identifier NCT02674217. RESULTS: One hundred and ninety-four females and 92 males were included; the median age was 47. All procedures were started on an outpatient basis and only 8 persons needed to be admitted to the hospital during the procedure. In order to obtain at least 1 × 106/kg viable CD34 cells, 1-4 aphereses were performed (median 1). The total number of viable CD34+ cells infused ranged between 1 and 19.2 × 106/kg (median 4.6). Patients recovered above 0.5 × 109/L absolute granulocytes on median day 8 (range 0-12). Two individuals needed red blood cells but none needed platelet transfusions. There were no transplant-related deaths and the 128-month overall survival of the patients is 100%. In 82 persons followed up for 3 or more months, the Expanded Disability Status Scale diminished from a mean of 5.2-4.9, the best results being obtained in relapsing-remitting and primary progressive MS. CONCLUSIONS: It is possible to conduct autotransplants for patients with MS employing non-frozen PBSCs and outpatient conduction. Additional information is needed to assess the efficacy of these procedures in the treatment of patients with MS.

More on the thrombocytopenia of the non-alcoholic fatty liver disease.

BACKGROUND: Using only serologic determinations, we have previously found that thrombocytopenia presents in less than one half of patients with non-alcoholic fatty liver disease (NAFLD). MATERIAL AND METHODS: Employing a more accurate method to define the presence of NAFLD, serologic determinations (Fibromax®) coupled with liver transient elastography (TE/Fibroscan®), we have prospectively studied a group of 211 individuals with a suspicion of a liver disease. RESULTS: NAFLD was identified in 81 individuals. In 48 persons another causes of liver damage were identified and discarded from further analysis. A subset of 33 patients with NAFLD without liver fibrosis or cirrhosis was analyzed. In eight of them (24%), thrombocytopenia (less than 150 × 109/l platelets) was identified. The presence of thrombocytopenia in this subset of persons was associated with overweight, was usually mild, above 50 × 109/l, was not associated to mucocutaneous bleeding and did not require treatment. CONCLUSIONS: NAFLD should be considered as a cause of mild thrombocytopenia. Our initial observation has been confirmed and defined more precisely. Additional studies are needed to further define more features of the thrombocytopenia of NAFLD, as well as its mechanisms.

IKAROS Gene Deleted B-Cell Acute Lymphoblastic Leukemia in Mexican Mestizos: Observations in Seven Patients and a Short Review of the Literature.

BACKGROUND: In B-cell acute lymphoblastic leukemia, one of the most frequent cytogenetic alterations is the presence of the Philadelphia chromosome. Recently, newly identified genetic alterations have been studied, among them the IKZF1 deletion. IKZF1 encodes IKAROS, a zinc finger protein that plays an important role in hematopoiesis involving the regulation process of adhesion, cellular migration, and as a tumor suppressor. OBJECTIVE: We aimed to study the impact of IKAROS deletion in the evolution and prognosis of B-cell acute lymphoblastic leukemia. MATERIALS AND METHODS: At a single center we prospectively studied patients diagnosed with B-cell acute lymphoblastic leukemia and screened for IKZF1 deletion using the multiplex ligation-dependent probe amplification method. We did a descriptive analysis of patients positive for the IKZF1 deletion to determine its impact on the evolution of the disease and survival rate. RESULTS: Between 2010 and 2015, 16 Mexican mestizo patients with B-cell acute lymphoblastic leukemia were prospectively screened for IKZF1 deletion; seven (43%) were positive and were included for further analysis. The age range of patients was 13-60 years; six were males and one female. All cases had type B acute lymphoblastic leukemia. Of the seven patients, two died, three were lost to follow-up, and two continue in complete remission with treatment. Results are worse than those in a group of patients with non-mutated IKAROS B-cell acute lymphoblastic leukemia previously studied in our center. CONCLUSIONS: Although this is a small sample, the presence of IKAROS deletion in acute lymphoblastic leukemia patients could represent a poor-prognosis marker and was probably related to therapy failure. It is also possible that this variant of leukemia may be more prevalent in Mexico. More studies are needed to define the role of IKZF1 deletion in acute lymphoblastic leukemia and the real prevalence of the disease in different populations.