Efficacy and safety of mammalian target of rapamycin inhibitors in systemic mastocytosis: A nationwide French pilot study.

Systemic mastocytosis (SM) corresponds to a rare and heterogeneous spectrum of diseases characterized by the accumulation of atypical mast cells (MCs). Advanced mastocytosis (Adv-SM) is associated with poor survival; in contrast, patients with non-advanced SM (non-Adv-SM) usually have a normal life expectancy but may experience poor quality of life. Despite recent therapeutic progress including tyrosine kinase inhibitors, new treatment options are needed for refractory and/or intolerant patients with both severely symptomatic and Adv-SM. In vitro, the mTOR pathway is activated in MCs from patients bearing the KIT D816V mutation. Furthermore, rapamycin induces the apoptosis of KIT D816V MCs selectively. In this nationwide study, we report the outcomes of patients diagnosed with SM and treated with a mammalian target of rapamycin inhibitor (imTOR) within the French National Reference Center for mastocytosis (CEREMAST). All patients registered were relapsing, treatment-refractory, or ineligible for other cytoreductive therapy. Non-Adv-SM patients received imTOR as a monotherapy (rapamycin/everolimus), and Adv-SM patients received imTOR as a monotherapy or in combination with cytarabine. The objective response rate (ORR) in non-Adv-SM was 60% (partial response in 40% and major response in 20%), including reductions in skin involvement, mediator release symptoms, and serum tryptase. In the Adv-SM group, the ORR was 20% (including one major response and one partial response, both in patients with a KIT D816V mutation), which enabled a successful bridge to allogeneic stem cell transplantation in one patient. Our results suggest that imTOR treatment has potential benefits in patients with SM harboring a KIT D816V mutation.

Pathophysiologic implications of elevated prevalence of hereditary alpha-tryptasemia in all mastocytosis subtypes.

BACKGROUND: Mastocytosis and monoclonal mast cell (MC) activation syndrome (MMAS) are heterogeneous conditions characterized by the accumulation of atypical MCs. Despite the recurrent involvement of KIT mutations, the pathophysiologic origin of mastocytosis and MMAS is unclear. Although hereditary α-tryptasemia (HαT, related to TPSAB1 gene duplication) is abnormally frequent in these diseases, it is not known whether the association is coincidental or causal. OBJECTIVE: We evaluated the prevalence of HαT in all mastocytosis subtypes and MMAS and assessed the pathophysiologic association with HαT. METHODS: Clinical data, laboratory data, KIT mutations, TPSAB1 duplication (assessed by droplet digital PCR), and HαT prevalence were retrospectively recorded for all patients with mastocytosis and MMAS registered in the French national referral center database and compared to a control cohort. To increase the power of our analysis for advanced systemic mastocytosis (advSM), we pooled our cohort with literature cases. RESULTS: We included 583 patients (27 with MMAS and 556 with mastocytosis). The prevalence of HαT in mastocytosis was 12.6%, significantly higher than in the general population (5.7%, P = .002) and lower than in MMAS (33.3%, P = .02). HαT+ patients were more likely to have anaphylactic reactions and less likely to have cutaneous lesions than HαT- patients (43.0% vs 24.4%, P = .006; 57.7% vs 75.6%, respectively, P = .006). In the pooled analysis, the prevalence of HαT was higher in advSM (11.5%) than in control cohorts (5.2%, P = .01). CONCLUSION: Here we confirm the increase incidence of anaphylaxis in HαT+ mastocytosis patients. The increased prevalence of HαT in all subtypes of systemic mastocytosis (including advSM) is suggestive of pathophysiologic involvement.

CPX-351 in higher risk myelodysplastic syndrome and chronic myelomonocytic leukaemia: a multicentre, single-arm, phase 2 study.

BACKGROUND: CPX-351, an encapsulated form of cytarabine and daunorubicin, has shown greater efficacy than the classic 3 + 7 treatment administration in secondary acute myeloid leukaemia. Given that higher-risk myelodysplastic syndrome and chronic myelomonocytic leukaemia share similarities with secondary acute myeloid leukaemia, we aimed to investigate the safety and efficacy of CPX-351 in this context. METHODS: This investigator-initiated two-cohort phase 2 trial was conducted by the Groupe Francophone des Myélodysplasies, with 12 participating centres in France. It comprised cohort A (reported here and completed), which included patients in first-line treatment, and cohort B, which was stopped for lack of inclusion (ie, not enough patients met the inclusion criteria), for patients with hypomethylating agent failure that is not reported here. Cohort A enrolled patients with newly diagnosed higher-risk myelodysplastic syndrome or chronic myelomonocytic leukaemia (aged 18-70 years old) with an Eastern Cooperative Oncology Group performance status of 0-1. Intravenous CPX-351 (100 mg/m2 cytarabine and 44 mg/m2 daunorubicin) was given on days 1, 3, and 5, with a second induction cycle given (same daily dose on days 1 and 3) if at least a partial response was not reached. Patients who responded could receive up to four monthly consolidation cycles (same daily dose on day 1) or allogeneic haematopoietic stem-cell transplantation (HSCT). Overall response rate after one or two induction courses according to European LeukemiaNet 2017 acute myeloid leukaemia was the primary endpoint after CPX-351 induction, whether patients received one or two induction cycles. Safety was assessed in all patients enrolled (in cohort A). This trial is registered with ClinicalTrials.gov, NCT04273802. FINDINGS: Between April 29, 2020, and Feb 10, 2021, 21 (68%) male and ten (32%) female patients were enrolled. 27 (87%) of 31 patients responded (95% CI 70-96). 16 (52%) of the 31 patients received at least one consolidation cycle. 30 (97%) of the 31 patients included were initially considered eligible for allogeneic HSCT and 29 (94%) of the 31 patients had the procedure. Median follow-up was 16·1 months (IQR 8·3-18·1). The most common grade 3-4 adverse events were pulmonary (eight [26%] of 31 patients) and cardiovascular (six [19%] of 31 patients). There were 14 serious adverse events (mainly hospitalisation for infection [n=5] and only one was treatment-related) and no treatment-related death. INTERPRETATION: CPX-351 appears to be active and safe in patients with higher-risk myelodysplastic syndrome and chronic myelomonocytic leukaemia, allowing bridging to allogenic HSCT in most patients. FUNDING: Jazz Pharmaceuticals.

[Vaccination before and after autologous hematopoietic cell transplantation for autoimmune diseases: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (MATHEC-SFGM-TC)]. / Vaccinations avant et après greffe de cellules hématopoïétiques autologues chez les patients atteints de maladies auto-immunes : propositions du groupe Maladies Auto-immunes et Thérapie Cellulaire de la SFGM-TC.

The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 12th workshop on hematopoietic stem cell transplantation clinical practices harmonization procedures on September 2021 in Lille, France. In the absence of specific national or international recommendation, the French working group for autologous stem Cell transplantation in Auto-immune Diseases (MATHEC) proposed guidances for vaccinations of patients undergoing autologous hematopoietic stem cell transplantation for autoimmune disease, including in the context of SARS-Cov-2 pandemic.

Outcome of febrile neutropenic patients treated for bacteriuria in hematology.

INTRODUCTION: Positive urine sample is a frequent finding in post-chemotherapy febrile neutropenia (FN) and can lead to prolonged antibiotic therapy. The aim of this study was to assess the outcome of bacteriuria episodes in FN patients receiving targeted antibiotic therapy. MATERIALS AND METHODS: A multi-centric retrospective study was conducted over a four-year period (2014-2019) on systematic urinalysis. All consecutive first bacteriuria episodes (≤ 2 bacteria with at least ≥ 103 CFU/mL) during FN in hospitalized adult patients for hematological malignancies were included. Relapse and recurrence were defined by fever or urinary tract symptoms (UTS) with the same bacterial subspecies in urine occurring ≤ 7 days and ≤ 30 days, respectively, after antibiotic discontinuation. Mortality rate was determined at 30 days. Targeted antibiotic therapy ≤ 10 days for women and ≤ 14 for men was considered as short course. RESULTS: Among 97 patients, 105 bacteriuria episodes on systematic urinalysis were analyzed; 67.6% occurred in women, 41.9% in AML patients, 17.1% were bacteremic, 14.2% presented with UTS, and 61.9% were treated with short-course antibiotic treatment. One death was reported. In men, no relapse/recurrence was noted, even in the short-course antibiotic group. In women, 2.8% of episodes treated with short-course antibiotic led to relapse or recurrence. CONCLUSIONS: Relapse, recurrence, and mortality were uncommon events in FN patients experiencing bacteriuria episode, whatever the antibiotic duration. To distinguish asymptomatic bacteriuria from infection remained challenging in women. In men, systematic urinalysis at onset of FN could be useful.

Decitabine Versus Hydroxyurea for Advanced Proliferative Chronic Myelomonocytic Leukemia: Results of a Randomized Phase III Trial Within the EMSCO Network.

PURPOSE: Hydroxyurea (HY) is a reference treatment of advanced myeloproliferative neoplasms. We conducted a randomized phase III trial comparing decitabine (DAC) and HY in advanced myeloproliferative chronic myelomonocytic leukemias (CMML). PATIENTS AND METHODS: Newly diagnosed myeloproliferative CMML patients with advanced disease were randomly assigned 1:1 to intravenous DAC (20 mg/m2/d days 1-5) or HY (1-4 g/d) in 28-day cycles. The primary end point was event-free survival (EFS), events being death and acute myelomonocytic leukemia (AML) transformation or progression. RESULTS: One-hundred seventy patients received DAC (n = 84) or HY (n = 86). Median age was 72 and 74 years, and median WBC count 32.5 × 109/L and 31.2 × 109/L in the DAC and HY arms, respectively. Thirty-three percent of DAC and 31% of HY patients had CMML-2. Patients received a median of five DAC and six HY cycles. With a median follow-up of 17.5 months, median EFS was 12.1 months in the DAC arm and 10.3 months in the HY arm (hazard ratio [HR], 0.83; 95% CI, 0.59 to 1.16; P = .27). There was no significant interaction between treatment effect and blast or platelet count, anemia, CMML Prognostic Scoring System, Groupe Francophone des Myelodysplasies, or CMML Prognostic Scoring System-mol risk. Fifty-three (63%) DAC patients achieved a response compared with 30 (35%) HY patients (P = .0004). Median duration of response was similar in both arms (DAC, 16.3 months; HY, 17.4 months; P = .90). Median overall survival was 18.4 months in the DAC arm and 21.9 months in the HY arm (P = .67). Compared with HY, DAC significantly reduced the risk of CMML progression or transformation to acute myelomonocytic leukemia (cause-specific HR, 0.62; 95% CI, 0.41 to 0.94; P = .005) at the expense of death without progression or transformation (cause-specific HR, 1.55; 95% CI, 0.82 to 2.9; P = .04). CONCLUSION: Compared with HY, frontline treatment with DAC did not improve EFS in patients with advanced myeloproliferative CMML (ClinicalTrials.gov identifier: NCT02214407).

Prospective validation of a biomarker-driven response prediction model to romiplostim in lower-risk myelodysplastic neoplasms - results of the EUROPE trial by EMSCO.

The EUROPE phase 2 trial investigated the predictive value of biomarkers on the clinical efficacy of single agent romiplostim (ROM) treatment in patients with lower-risk myelodysplastic neoplasms (LR-MDS) and thrombocytopenia within the 'European Myelodysplastic Neoplasms Cooperative Group' (EMSCO) network. A total of 77 patients with LR-MDS and a median platelet count of 25/nl were included, all patients received ROM at a starting dose of 750 µg by SC injection weekly. Thirty-two patients (42%) achieved a hematologic improvement of platelets (HI-P) with a median duration of 340 days. Neutrophil (HI-N) and erythroid (HI-E) responses were observed in three (4%) and seven (9%) patients, respectively. We could not confirm previous reports that HI-P correlated with baseline endogenous thrombopoietin levels and platelet transfusion history, but SRSF2 mutation status and hemoglobin levels at baseline were significantly linked to HI-P. Sequential analysis of variant allelic frequency of mutations like SRSF2 did not reveal an impact of ROM on clonal evolution in both responders and non-responders. In summary, our study confirms the safety and efficacy of ROM in LR-MDS patients and may allow to better define subgroups of patients with a high likelihood of response.

Efficacy of antibiotic short course for bloodstream infections in acute myeloid leukemia patients with febrile neutropenia: A retrospective comparative study.

OBJECTIVES: There is no specific recommendation about antimicrobial treatment length for documented infections in chemotherapy induced febrile neutropenia (FN). Practices have changed along time in our center regarding length of antibiotic treatment. The aim of this study was to compare long versus short antibiotic course for bloodstream infection (BSI) treatment in acute myeloid leukemia (AML) patients during FN. METHODS: This monocentric retrospective comparative study included all consecutive BSI episodes among AML patients with FN for 3 years (2017-2019). Episodes were classified regarding the length of antibiotic treatment, considered as short course if the treatment lasted ≤ 7 days, except for nonfermenting bacteria and Staphylococcus aureus or lugdunensis for which the threshold was ≤ 10 days and ≤ 14 days, respectively. The primary outcome was the number of BSI relapses in both groups within 30 days of antibiotic discontinuation. RESULTS: Among 71 AML patients, 104 BSI episodes were included; 48 (46%) received short course treatment. Only 8 (7.6%) BSI episodes relapsed within 30 days of antibiotic discontinuation, 5 having received short course treatment. No association was found between risk of relapse and short course of antibiotic treatment (p = 0.37). The only risk factor significantly associated with BSI relapse was neutropenia duration (p = 0.005). CONCLUSION: Antibiotic short course seemed as effective as prolonged treatment for BSI in AML patients during FN, with very few relapses at day 30. These encouraging findings should be confirmed through prospective studies.

Late Onset of Chronic Granulomatous Disease Revealed by Paecilomyces lilacinus Cutaneous Infection.

Chronic granulomatous disease (CGD) is an inherited immunodeficiency due to defective leukocyte NADPH responsible for recurrent infections and aberrant inflammation. Mutations in the CYBB gene are responsible for the X-linked CGD and account for approximately 70% of the cases. CGD is diagnosed during childhood in males. Female carriers may have biased X-inactivation and may present with clinical manifestations depending on the level of residual NADPH oxidase activity. We report the case of a previously asymptomatic female carrier who was diagnosed at age 67 with a skin infection with the rare fungus Paecilomyces lilacinus as the first manifestation of CGD. Dihydrorhodamine 123 (DHR) activity was below 10%. Next-generation sequencing (NGS) revealed mutations in DNMT3A, ASXL1, and STAG2 suggesting that clonal hematopoiesis could be responsible for a progressive loss of NADPH oxidase activity and the late onset of X-linked CGD in this patient. Long-term follow-up of asymptomatic carrier women seems to be essential after 50 years old.

[Crohn's disease and autologous hemapoietic cell transplantation: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Indications de l'autogreffe de cellules hématopoïétiques dans la Maladie de Crohn : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire.

Crohn's Disease (CD) is an auto-inflammatory disease, which may involve the entire gastro-intestinal tract. CD is diagnosed on several clinical, biological, endoscopic and histological criteria. First line therapy is based on oral or iv steroids. In case of steroids dependence or resistance, several types of immunosuppressive or immunomodulating therapies are available: classical antimetabolites (thiopurines or methotrexate) or monoclonal antibodies against TNFα, against interleukin 12/23 or against integrin. Nonetheless, Crohn's disease may remain active despite the use of several lines of therapy. In such cases, autologous hematopoietic cell transplantation (AHCT) is an effective therapeutic option in highly selected CD patients with specific criteria. The MATHEC-SFGM-TC Good Clinical Practice Guidelines (GCPG) were developed by a multidisciplinary group of experts including gastroenterologists, hematologists and members of the reference center for stem cell therapy in auto-immune diseases (MATHEC), including members of the French groupe d'étude thérapeutique des affections inflammatoires du tube digestif(GETAID) under the auspices of the French speaking Society of bone marrow transplantation and cellular therapy (SFGM-TC). The aim of the present guidelines is to define the eligibility criteria for CD patients when candidates to AHCT, the procedures for mobilization of hematopoietic stem cell (HSC), conditioning regimen and standardized follow-up after AHCT including monitoring of gastroenterological treatments during AHCT and thereafter throughout all follow-up.

[Indication of autologous stem cell transplantation in chronic inflammatory demyelinating polyneuropathy: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Indications de l'autogreffe de cellules souches hématopoïétiques dans la polyradiculonévrite inflammatoire démyélinisante chronique : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a chronic autoimmune disease involving the peripheral nervous system, characterized by focal and segmental demyelination accounting for neurological deficit. CIDP diagnosis is based on several criteria and requires the presence of specific clinical symptoms and of demyelinating criteria on the electroneuromyogram (ENMG) or of additional supportive criteria (spinal fluid examination with dissociation between albumin level and cellular abnormalities, nervous abnormalities on MRI or other minor abnormalities on ENMG, demyelinating features on nerve biopsy or patient improvement under so-called first-line therapy with immunodulator treatment). After failure of two successive first line immunomodulating drug therapies (corticosteroids, immunomodulating immunoglobulins, or plasma exchange), several options can be considered as second line therapies. The efficacy of autologous hematopoietic cell transplantation (AHCT) has been shown in CIDP patients. The aim of these recommendations established by a working group of experts from the "Société française de greffe de moelle osseuse et thérapie cellulaire (SFGM-TC)", the group "maladies auto-immunes et thérapie cellulaire (MATHEC)" and the "filière de santé maladies rares neuromusculaire (FILNEMUS)" is to specify the eligibility criteria for AHCT in CIPD patients, to describe the mobilization and the conditioning regimen for the AHCT procedure, as well as the patient standardized post-transplant follow-up and the management of neurological treatment throughout the all procedure.

Long-term molecular remission in a patient with acute myeloid leukemia harboring a new NUP98-LEDGF rearrangement.

A large variety of molecular rearrangements of the NUP98 gene have been described in the past decades (n = 72), involving fusion partners coding for different transcription factors, chromatin modifying enzymes, as well as various cytosolic proteins. Here, we report the case of an AML-M2 patient with a variant NUP98-LEDGF/PSIP1 gene fusion (N9-L10). In this patient, three different NUP98-LEDGF fusion mRNAs were characterized due to alternative splicing in LEDGF exon 11. Targeted high-throughput sequencing revealed the presence of IDH1, SRSF2, and WT1 additional pathogenic mutations. To improve the therapeutic monitoring, quantification of NUP98-LEDGF mRNA by real-time PCR was developed. Because of poor response to conventional chemotherapy, allogeneic stem cell transplantation was performed, followed by 20 cycles of azacitidine-based preemptive treatment of relapse. More than 31 months after diagnosis, corresponding to 25 months post SCT and 4 months after the last cycle of azacytidine, the patient is in complete molecular remission (undetectable NUP98-LEDGF mRNA transcripts). This study highlights the considerable variability in breakpoint location within both NUP98 and LEDGF, associated with alternative splicing affecting LEDGF. It also emphasizes the need to fully characterize the breakpoints within the two genes and the identification of all fusion mRNAs, particularly for the development of a molecular monitoring assay. All these data seem critical for the optimal management of NUP98-LEDGF + hematological malignancies commonly associated with a poor prognosis.

Extending autologous transplantation as first line therapy in multiple myeloma patients with severe renal impairment: a retrospective study by the SFGM-TC.

Renal impairment is a common complication of multiple myeloma (MM), accounting for 20-30% of MM patients at diagnosis and 40-50% of patients during the course of their disease. This feature is associated with poor prognosis and shorter survival as compared to patients with normal renal function (NRF). Therefore, therapeutic management is challenging as autologous stem cell transplantation (ASCT) is often not considered as a valuable strategy, mainly due to concerns of toxicity. In this retrospective and multicenter study, we included 55 MM patients with dialysis-dependent or independent renal failure who underwent high-dose melphalan-based ASCT in order to assess the efficacy outcomes and toxicities of this strategy. Response to ASCT was at least VGPR (very good PR) in 58% of patients and 96% of patients who also received bortezomib-based induction were at least in PR after ASCT. Median OS was 76 months and median PFS was 55 months, similarly to MM patients with NRF. In multivariate analysis, dose of melphalan (140 mg/m2) was correlated with better PFS (18 months, P = 0.005). Toxicities included febrile neutropenia (75%) and severe mucositis (34%). Overall, this work confirmed that ASCT conditioned by 140 mg/m2 melphalan is a beneficial procedure for MM patients with renal failure.

Mild cognitive impairment (MCI) and dementia in a sample of adults in the city of Bogotá / Comprometimento cognitivo leve (CCL) e demência em uma amostra de adultos na cidade de bogotá

ABSTRACT The low prevalence of dementia described in communities is likely due to the low sensitivity of screening tests and an absence of evaluation by specialists. OBJECTIVE: To estimate the prevalence of mild cognitive impairment (MCI) and dementia in adults older than 50 years. METHODS: A two-phase, cross-sectional study was conducted by specialists to evaluate cognition and associated demographic risk factors in 1,235 independent community-dwelling adults from Bogotá. In Phase I, screening was performed using the MMSE and MoCA tests. In Phase II, after application of a comprehensive neuropsychological battery with neurologic and psychiatric evaluations, a cognitive diagnosis was established by consensus. RESULTS: The prevalence found for MCI was 34% and for dementia was 23%. MCI was associated with incomplete high school, OR=1.74 (95%CI=1.23-2.45), and with an age of 70-79 years, OR=1.93 (95%CI=1.47-2.53). A total of 73% of MCI cases were amnestic. Dementia was associated with incomplete primary education, OR=8.98 (95%CI=5.56-14.54), complete primary education, OR=6.23 (95%CI=3.70-10.47), and age older than eighty years, OR=3.49 (95%CI=2.23-5.44). CONCLUSION: The prevalence of dementia found was greater than the rates reported in previous studies. Low educational level was the main risk factor for cognitive impairment and should be considered in strategic planning for the local health system.

RESUMO A baixa prevalência de demência relatada em comunidades deve ser devida ao emprego de testes de rastreio de baixa sensibilidade e à falta da avaliação por especialistas. OBJETIVO: Estimar a prevalência de comprometimento cognitivo leve (CCL) e demência em adultos com idade superior a 50 anos. MÉTODOS: Um estudo transversal de duas fases realizado por especialistas, avaliando a cognição e os fatores de risco demográficos associados, com 1.235 adultos autônomos da comunidade em Bogotá. Em uma Fase I, foram realizados os testes de rastreio MEEM e MoCA. Na Fase II, após uma ampla bateria neuropsicológica com avaliações neurológicas e psiquiátricas, foi estabelecido um diagnóstico cognitivo por consenso. RESULTADOS: A prevalência encontrada de CCL foi de 34% e de demência, de 23%. CCL foi associado a ensino médio incompleto, OR=1,74 (IC 95%=1,23-2,45) e idade entre 70-79 anos, OR=1,93 (IC 95%=1,47-2,53). Entre os casos de CCL, 73% eram amnésticos. A demência foi associada a ensino fundamental incompleto, OR=8,98 (IC 95%=5,56-14,54), ensino fundamental completo, OR=6,23 (IC 95%=3,70-10,47) e idade superior a oitenta anos, OR=3,49 (IC 95%=2,23-5,44). CONCLUSÃO: A prevalência de demência encontrada é maior do que a relatada em estudos prévios. O baixo nível educacional foi o principal fator de risco para declínio cognitivo e deve ser considerado no planejamento estratégico do nosso sistema de saúde.

Deterioro cognitivo y factores de riesgo cardiovascular y metabólico en una muestra de adultos de Bogotá / Cardiovascular and metabolic risk factors, for cognitive impairment in adults from Bogotá

Introducción: la relación entre los factores de riesgo cardiovascular (FRCV) y los factores metabólicos con deterioro cognitivo (DC), definido como deterioro cognitivo leve (DCL) o demencia, es controversial. Objetivo: describir los FRCV y metabólicos relacionados con DC, en una muestra de adultos de Bogotá. Material y métodos: se diseñó un estudio de corte transversal y se evaluó el estado cognitivo en dos fases, en adultos mayores de 50 años, autónomos, no institucionalizados, aplicando pruebas neuropsicológicas y un protocolo de evaluación neuropsiquiátrica. Los FRCV y metabólicos fueron documentados por autoreporte, y se tomaron medidas antropométricas. Resultados: en 1.045 adultos estudiados, el promedio de edad fue de 68 años (DS 8.6), y de educación 8 años (DS 6.0), 76 % fueron mujeres, 56 % presentaba hipertensión arterial (HTA), 40 % dislipidemia, 37 % fueron fumadores, 37 % tenían sobrepeso, 28 % hipotiroidismo, 25 % obesidad, 17 % consumían alcohol y 16 % eran diabéticos. El DCL se asoció con escolaridad de primaria-incompleta OR:1.94 (95 % IC: 1.21- 3.14), primaria-completa OR:1.96 (95 % IC: 1.18- 3.25), bachillerato- incompleto OR:3.01 (95 % IC: 1.80-5.05), bachillerato-completo OR: 2.54 (95 % IC: 1.45- 4.45) y con edad entre 70 y 79 años OR:2.06 (95% IC: 1.32-3.23). La demencia se asoció con escolaridades de primaria-incompleta OR: 11.20 (95 % IC: 4.99- 25.12), primaria-completa OR: 7.91 (95 % IC: 3.44-18.16), bachillerato- incompleto OR: 2.87 (95 % IC: 1.17- 7.01) y con edades entre 70 -79 años OR: 2.82. (95 % IC: 1.37-5.80), o mayores de 80 años OR: 7.68 (95 % IC: 3.49- 16.90) y con sufrir HTA OR: 1.45 (95 % IC: 1.03-2.05). Conclusión: la baja escolaridad, una edad avanzada y sufrir HTA son en su orden los factores más importantes para el desarrollo de la demencia. Los adultos entre 70 y 79 años con bachillerato incompleto, tienen mayor riesgo de DCL.

Introduction: The relationship between some metabolic and cardiovascular risk factors (CVRF) and cognitive impairment (CI) defined as mild cognitive impairment (MCI) and dementia, is controversial. Objective: Describe the cardiovascular and metabolic risk factors that are associated with cognitive impairment in adults from Bogotá. Materials and methods: A cross-sectional study, where the state of cognitive functions (normal, MCI or dementia) was evaluated in two phases, in adults older than 50 years, autonomous, non-institutionalized, using neuropsychological tests and neuropsychiatric protocol. Its cardiovascular and metabolic risk by self-reported history and standardized anthropometric measurements were documented. Results: Of 1045 adults surveyed, the mean age of the group was 68 years(SD 8.6), and the mean education level was 8 years(SD 6.0), 76% were women, 56% had hypertension(HT), 40% dyslipidemia, 37% were smokers, 36% were overweight, 28% presented hypothyroidism, 25% were obese, 17% drank alcohol and 16% were diabetic. MCI was associated with incomplete high school education OR:3.01(95% CI 1.80-5.05) and aged between 70 and 79 years OR:2.06(95%CI 1.32-3.23). Dementia was associated with lower scholarity, incomplete-primary OR:11.20(95%CI 4.99-25.12), complete-primary OR 7.91(95% CI.3.44-18.16), incomplete-high school OR: 2.87(95% CI 1.17-7.01), age over 80 years OR:7.68(95%CI 3.49-16.90); and suffer hypertension OR:1.45(95%CI 1.03- 2.05) Conclusion: Low education, older age and hypertension are in order, the most important risk factors for the development of dementia in our population. Adults between 70 and 79 with incomplete high school have higher risk of MCI.

Acuerdo intra-interobservador en las pruebas Minimental State Examination (MMSE) y Montreal Cognitive Assessment (MoCA test) aplicados por personal en entrenamiento / Intra and interrater reliability of the Minimental State Exmination (MMSE) and Montréal Cognitive Assessment (MoCA test) applied by health personnel in training

Introducción: en el proceso del diagnóstico neuropsicológico, los instrumentos de tamizaje cognitivo, son una herramienta útil en la identificación de cambios mentales del sujeto, en momentos puntuales o a través del tiempo. Su uso se fundamenta en el análisis psicométrico. Objetivo: determinar el acuerdo inter e intra-observador en el MoCA test y el MMSE, aplicado por profesores y estudiantes en procesos de entrenamiento de tamización cognitiva. Materiales y métodos: a los estudiantes y profesores en entrenamiento en la puntuación del MoCA test y el MMSE, se les presentó un video en dos sesiones, con un intervalo de 5 meses, mostrando el desempeño de dos adultos mayores, respondiendo el MoCA test y el MMSE, previo consentimiento informado. Se compararon los puntajes dados en las dos sesiones por los sujetos en entrenamiento, con los de ellos mismos (intra-observador), usando el coeficiente de concordancia y correlación de Lin(rho) y con los del grupo restante (inter-observador) usando el coeficiente de correlación intra-clase (ICC). Resultados: participaron 46 evaluadores. Se encontró alta confiabilidad inter-observador para el MoCA (ICC=0.86), pero baja para el MMSE (ICC=0.24) y baja confiabilidad intra-observador tanto para el MoCA (rho paciente 1=0.012 y rho paciente 2=0.152) como para el MMSE (rho paciente 1=0.008 y rho paciente 2=0.012). Aunque los puntajes difirieron, las clasificaciones diagnósticas realizadas por los evaluadores fueron similares a las del patrón de oro. Conclusión: la correcta aplicación del test, requiere varios entrenamientos, y aunque hubo pocas diferencias entre los puntajes, los errores cuando se está cerca del punto de corte propuesto, aumentan el riesgo de sesgo.

Introduction: The instruments for screening cognitive functions, applied to subjects in clinical settings and research, are useful for determining if this person has any trouble in cognition or show changes in the time. The usefulness of these instruments is defined with the evaluation of their psychometrics properties. Objective: This study allows to determine the intra and inter-observer agreement, when the MoCA test and MMSE were applied by a group in training process Materials and methods: The study group who attended two training sessions, with an interval of 5 months, scored the MoCA test and MMSE, from two patients which were filmed responding the tests, previous informed consent signature. We compared how close were the scores of participants among themselves by concordance correlation coefficient of Lin (rho) and with those given from the others by intra-class correlation coefficients (ICC). Results: In total, 46 participants were included. Intra-rater reliability was high for MoCA test (ICC = 0.86), but it was poor for MMSE (ICC=0.24). Inter-rater was poor for MoCA test (rho patient 1= 0.012, rho patient 2= 0.152) and MMSE (rho patient 1 = 0.008, rho patient 2 = 0.012). Although the scores between participants and gold standard were different, the diagnoses were similar. Conclusion:The correct scoring of the test, requires several trainings to clinical and research groups, and although they can be found few differences between scores applied by non-expert personnel, if the scores mistakenly given, are close to the cut-of point proposed for each test, the bias increases.

Sincronización del estro en cerdas nulíparas y primíparas / Estrus synchronization in gilts and sows

Con el objeto de evaluar diferentes tratamientos para logar la sincronización del estro se realizaron dos experimentos. En el primer experimento se formaron 3 grupos con 30 animales cada uno (grupo 1, manejo convencional; grupo 2, Altrenogest; grupo 3, macho vasectomizado). En el segundo experimento, se formaron 2 grupos de 30 cerdas cada uno (grupo A, destete convencional; grupo B, Altrenogest). Los resultados fueron los siguientes: En el primer experimento: La edad a ingreso, fertilidad, promedio de lechones nacidos vivos, el número de lechones nacidos muertos, los lechones momificados y el promedio total de lechones nacidos, todos sin signficancia estadística (P>0.05). En cuanto al número de estro detectados y al número de hembras sincronizadas sí se encontró significancia estadística (P<0.05). En el segundo experimento: Los días de lactancia, el promedio de lechones destetados, la fertilidad, el promedio de lechones nacidos vivos, el número de lechones nacidos muertos y el promedio total de lechones nacidos, todos sin significancia estadística (P>0.05). sólo en el caso de los estros detectados se encontró significancia estadística (P<0.05). Se concluye que para el caso de las cerdas nulíparas, es recomendable la utilización del Altrenogest para la sincronización del estro y con ello reducir el ciclo reproductivo de la hembra. En cuanto a las hembras primípara es posible evitar la utilización de productos exógenos o manejos especiales, si el manejo convencional en las áreas reproductivas es eficiente

Control y erradicación de la enfermedad de Aujeszky en un sistema múltiple de tres sitios de producción / Control and eradication of Aujeszky's disease in a multiple site production system

El objetivo del presente trabajo fue controlar y erradicar la enfermedad de Aujeszky (EA) en un sistema múltiple de tres sitios de producción por medio de la vacunación del hato reproductor contra la EA,, la segregación de la descendencia y hacer una valoraicón lineal epidemiológica de los tres sitios de producción mediante el uso de animales centinelas libres de la EA. La seropositividad en los tres sitios fue del 93.67 por ciento de las muestras totales tomadas (1389) en todo el sistema por la prueba de seroneutralización SN y ELISA competitiva g1. Para la erradicación de la EA se vacunó a las hembras con una vacuna con deleción g1+, siendo revacuadas a los 21 días y cada 3 meses durante el primer año posterior al brote al igual que a todo el hato, durante el segundo año se vacunó al pie de cría cada 4 meses. Por otra parte, durante el brote los lechones fueron destetados a los 21 días y llevados a otras instalaciones fuera del sistema y cuando los signos clínicos desaparecieron, los lechones fueron destetados a los 18 días y segregados al sitio 2. En la mayoría de los muestreos serológicos se obtuvo 0 por ciento de seropositividad, excepto en uno de éstos. En este sentido se tiene que los métodos aplicados en el sitio 1 (vacunación, medicación, cerrar la entrada de animales al sitio por un tiempo y la segregación de la descendencia) fueron efectivos para controlar y erradicar la enfermedad de Aujeszky en el sistema, ya que desde que se inició el programa no se presentó un solo caso de la enfermedad en los sitios 2 y 3 del sistema, como tampoco se observaron signos clínicos de la EA en el sitio 1