Mortal Interaction Between Hemophagocytic Syndrome and Newly Developed Heart Failure. / Interação Letal entre Síndrome Hemofagocítica e Insuficiência Cardíaca Recentemente Desenvolvida.

BACKGROUND: Hemophagocytic syndrome (HPS) ia s devastating hyperinflammatory syndrome. Heart failure (HF) with preserved ejection fraction (HFpEF) status is closely correlated with increased inflammation, both systemic and intramyocardial. OBJECTIVES: This study sought to determine mortality predictors and reliable follow-up parameters in HPS that developed HFpEF during the clinical course. METHOD: Thirty-nine patients, diagnosed as HPS, according to HLH 2004 diagnostic criteria, with an HScore of ≥169 and proven bone marrow aspiration or biopsy, were recruited retrospectively. Both traditional, serum C-reactive protein, albumin and ferritin levels with lymphocyte, and platelet counts, as well as non-traditional risk factors, neutrophil-to-lymphocyte count (NLR), monocyte-to-lymphocyte count (MLR), mean platelet volume (MPV), and N-Terminal pro-brain natriuretic peptide (NTproBNP), were investigated retrospectively. The relationship between time-changed laboratory values both among themselves and with mortality. The overall significance level was set at 5%. RESULTS: This study showed that temporal change of cardiothoracic ratio (CTR), serum NTproBNP, ferritin, CRP, and albumin levels were detected as mortality predictors (p<0.05, for all) in the univariate analysis. Lymphocyte and platelet counts with NLR and MPV values were also significant (p<0.05). The relationship between NT-proBNP and increased systemic inflammatory markers proved to be significant. In addition to traditional risk factors, serum ferritin levels, NLR, MLR, and MPV levels also proved to be significantly correlated with each other. CONCLUSION: Accompanied by reliable follow-up parameters, rapid diagnosis and aggressive anti-inflammatory treatment with tight volume control can be life-saving in HPS patients who suffer from HFpEF. Close monitoring of inflammation may predict the outcome of patients suffering from HFpEF.

FUNDAMENTO: A síndrome hemofagocítica (SHF) é uma síndrome hiperinflamatória debilitante. O status da insuficiência cardíaca (IC) com fração de ejeção preservada (ICFEP) está intimamente relacionado ao aumento da inflamação sistêmica e intramiocárdica. OBJETIVOS: este estudo pretende determinar os preditores de mortalidade e os parâmetros de monitoramento confiáveis nos casos de SHF que desenvolveram a ICFEP durante seu curso clínico. MÉTODOS: Trinta e nove pacientes, diagnosticados com SHF de acordo com os critérios diagnósticos do estudo HLH 2004 com Hscore ≥169, e com aspiração ou biópsia de medula óssea comprovada, foram recrutados retrospectivamente. Foram investigados retrospectivamente os fatores de risco tradicionais, como proteína C reativa sérica, níveis de albumina e ferritina com contagens de linfócitos e plaquetas, e fatores não tradicionais, como relação neutrófilolinfócito (NLR), relação linfócito-monócito (MLR), volume plaquetário médio (MPV) e pró-peptídeo natriurético cerebral N-terminal (NTproBNP). Analisou-se a relação entre os valores laboratoriais alterados ao longo do tempo entre si e com a mortalidade. O nível de significância geral foi de 5%. RESULTADOS: Foi demonstrado que a alteração temporal dos níveis de índice cardiotorácico (ICT), NTproBNP sérico, ferritina, PCR e albumina foram detectados como sendo preditores de mortalidade (p<0,05, para todos) em análise univariada. As contagens de linfócitos e plaquetas com valores de NLR e MPV também foram significativos (p<0,05). A relação entre NT-proBNP e o aumento dos marcadores inflamatórios sistêmicos também foi considerada significativa. Além de fatores de risco tradicionais, os níveis de ferritina sérica, e os níveis de NLR, MLR e MPV foram considerados significativamente correlacionados entre si. CONCLUSÃO: Acompanhado de parâmetros de monitoramento confiáveis, o diagnóstico rápido e o tratamento antiinflamatório agressivo com controle rígido de volume podem salvar vidas de pacientes com SHF que sofrem de complicações por ICFEP. O monitoramento rígido da inflamação pode prever o resultado do paciente que sofre de ICFEP.

Interação Letal entre Síndrome Hemofagocítica e Insuficiência Cardíaca Recentemente Desenvolvida / Mortal Interaction Between Hemophagocytic Syndrome and Newly Developed Heart Failure

Resumo Fundamento: A síndrome hemofagocítica (SHF) é uma síndrome hiperinflamatória debilitante. O status da insuficiência cardíaca (IC) com fração de ejeção preservada (ICFEP) está intimamente relacionado ao aumento da inflamação sistêmica e intramiocárdica. Objetivos: este estudo pretende determinar os preditores de mortalidade e os parâmetros de monitoramento confiáveis nos casos de SHF que desenvolveram a ICFEP durante seu curso clínico. Métodos: Trinta e nove pacientes, diagnosticados com SHF de acordo com os critérios diagnósticos do estudo HLH 2004 com Hscore ≥169, e com aspiração ou biópsia de medula óssea comprovada, foram recrutados retrospectivamente. Foram investigados retrospectivamente os fatores de risco tradicionais, como proteína C reativa sérica, níveis de albumina e ferritina com contagens de linfócitos e plaquetas, e fatores não tradicionais, como relação neutrófilolinfócito (NLR), relação linfócito-monócito (MLR), volume plaquetário médio (MPV) e pró-peptídeo natriurético cerebral N-terminal (NTproBNP). Analisou-se a relação entre os valores laboratoriais alterados ao longo do tempo entre si e com a mortalidade. O nível de significância geral foi de 5%. Resultados: Foi demonstrado que a alteração temporal dos níveis de índice cardiotorácico (ICT), NTproBNP sérico, ferritina, PCR e albumina foram detectados como sendo preditores de mortalidade (p<0,05, para todos) em análise univariada. As contagens de linfócitos e plaquetas com valores de NLR e MPV também foram significativos (p<0,05). A relação entre NT-proBNP e o aumento dos marcadores inflamatórios sistêmicos também foi considerada significativa. Além de fatores de risco tradicionais, os níveis de ferritina sérica, e os níveis de NLR, MLR e MPV foram considerados significativamente correlacionados entre si. Conclusão: Acompanhado de parâmetros de monitoramento confiáveis, o diagnóstico rápido e o tratamento antiinflamatório agressivo com controle rígido de volume podem salvar vidas de pacientes com SHF que sofrem de complicações por ICFEP. O monitoramento rígido da inflamação pode prever o resultado do paciente que sofre de ICFEP.

Abstract Background: Hemophagocytic syndrome (HPS) ia s devastating hyperinflammatory syndrome. Heart failure (HF) with preserved ejection fraction (HFpEF) status is closely correlated with increased inflammation, both systemic and intramyocardial. Objectives: This study sought to determine mortality predictors and reliable follow-up parameters in HPS that developed HFpEF during the clinical course. Method: Thirty-nine patients, diagnosed as HPS, according to HLH 2004 diagnostic criteria, with an HScore of ≥169 and proven bone marrow aspiration or biopsy, were recruited retrospectively. Both traditional, serum C-reactive protein, albumin and ferritin levels with lymphocyte, and platelet counts, as well as non-traditional risk factors, neutrophil-to-lymphocyte count (NLR), monocyte-to-lymphocyte count (MLR), mean platelet volume (MPV), and N-Terminal pro-brain natriuretic peptide (NTproBNP), were investigated retrospectively. The relationship between time-changed laboratory values both among themselves and with mortality. The overall significance level was set at 5%. Results: This study showed that temporal change of cardiothoracic ratio (CTR), serum NTproBNP, ferritin, CRP, and albumin levels were detected as mortality predictors (p<0.05, for all) in the univariate analysis. Lymphocyte and platelet counts with NLR and MPV values were also significant (p<0.05). The relationship between NT-proBNP and increased systemic inflammatory markers proved to be significant. In addition to traditional risk factors, serum ferritin levels, NLR, MLR, and MPV levels also proved to be significantly correlated with each other. Conclusion: Accompanied by reliable follow-up parameters, rapid diagnosis and aggressive anti-inflammatory treatment with tight volume control can be life-saving in HPS patients who suffer from HFpEF. Close monitoring of inflammation may predict the outcome of patients suffering from HFpEF.

In vivo performance of different scaffolds for dental pulp stem cells induced for odontogenic differentiation.

This study was designed to determine the in vivo performance of three different materials as scaffolds for dental pulp stem cells (DPSC) undergoing induced odontogenic differentiation. An odontogenic medium modified by the addition of recombinant human bone morphogenetic protein 2 was used in the experimental groups to induce differentiation. Mesenchymal stem cell medium was used in the control groups. DPSC were transplanted onto the backs of mice via three scaffolds: copolymer of L-lactide and DL-lactide (PLDL), copolymer of DL-lactide (PDL) and hydroxyapatite tricalcium phosphate (HA/TCP). The expression levels of dentin sialo-phosphoprotein (DSPP), dentin matrix protein-1 (DMP1), enamelysin/matrix metalloproteinase 20 (MMP20) and phosphate-regulating gene with homologies to endopeptidases on X chromosome (PHEX) were analysed using RT-PCR. The expressions in the experimental groups were compared to those in the control groups. The transcript expressions at 6 and 12 weeks were significantly different for all scaffolds (p < 0.05), except for the expression of DSPP in the PLDL group with regard to the time variable. Although there was a decrease in the expression of enamelysin/MMP20 in PLDL and HA/TCP at 12 weeks, all other expressions increased and reached their highest level at 12 weeks. The highest DSPP expression was in the PDL group (p < 0.05). The highest expression of DMP1 was detected in the HA/TCP group (p < 0.05). The highest expression of PHEX was in the PLDL group (p < 0.05). Consequently, PLDL and PDL seemed to be promising scaffold candidates for odontogenic regeneration at least as HA-TCP, when they were applied with the DPSC induced for odontogenic differentiation.

Bacteriological profile in conjunctival, lacrimal sac, and nasal specimens and conjunctival normalization time following external, endoscopic, and transcanalicular multidiode laser dacryocystorhinostomy.

PURPOSE: To compare the conjunctival, lacrimal sac, and nasal flora cultures and conjunctival normalization time following external (EX-), endoscopic (EN-), and transcanalicular multidiode laser (TC-) dacryocystorhinostomy (DCR) and to evaluate the relationship between culture positivity and surgical success. We further performed antibiotic sensitivity analyses for lacrimal sac culture samples. METHODS: A total of 90 patients with primary acquired nasolacrimal duct obstruction were recruited and divided into EX-DCR (n=32), EN-DCR (n=28), and TC-DCR (n=30) groups. Conjunctival, nasal, and lacrimal sac cultures and antibiograms were analyzed. RESULTS: In all three groups, coagulase-negative Staphylococcus (CNS) was predominantly isolated preoperatively from the conjunctiva, nose, and lacrimal sac and postoperatively from the conjunctiva. Preoperative and postoperative conjunctival culture positivity rates were similar between all the groups (p>0.05). A statistically significant difference in the growth rate of culture in the lacrimal sac was observed between the three groups (p=0.001). CNS and Staphylococcus aureus cultures were predominantly sensitive to linezolid, teicoplanin, tigecycline, vancomycin, and mupirocin. Conjunctival normalization times were similar between the three groups (p>0.05). Anatomical and functional success rates were not found to be significantly correlated with preoperative conjunctival and lacrimal sac culture positivity (p>0.05). CONCLUSIONS: Similar rates of preoperative and 1-week postoperative conjunctival culture positivity were observed in all the groups; a significantly lower bacterial growth rate was observed in postoperative conjunctival cultures. CNS was the most commonly isolated organism. Bacterial growth rates in the lacrimal sac samples were significantly higher in the EN-DCR group. Bacterial growth rates obtained preoperatively from the conjunctival and lacrimal sac culture samples were not correlated with DCR success.

Bacteriological profile in conjunctival, lacrimal sac, and nasal specimens and conjunctival normalization time following external, endoscopic, and transcanalicular multidiode laser dacryocystorhinostomy / Perfil bacteriológico e tempo de normalização conjuntival de espécimes de conjuntiva, saco lacrimal e nasais após dacriocistorrinostomia externa, endoscópica e transcanalicular com laser de multi diodo

ABSTRACT Purpose: To compare the conjunctival, lacrimal sac, and nasal flora cultures and conjunctival normalization time following external (EX-), endoscopic (EN-), and transcanalicular multidiode laser (TC-) dacryocystorhinostomy (DCR) and to evaluate the relationship between culture positivity and surgical success. We further performed antibiotic sensitivity analyses for lacrimal sac culture samples. Methods: A total of 90 patients with primary acquired nasolacrimal duct obstruction were recruited and divided into EX-DCR (n=32), EN-DCR (n=28), and TC-DCR (n=30) groups. Conjunctival, nasal, and lacrimal sac cultures and antibiograms were analyzed. Results: In all three groups, coagulase-negative Staphylococcus (CNS) was predominantly isolated preoperatively from the conjunctiva, nose, and lacrimal sac and postoperatively from the conjunctiva. Preoperative and postoperative conjunctival culture positivity rates were similar between all the groups (p>0.05). A statistically significant difference in the growth rate of culture in the lacrimal sac was observed between the three groups (p=0.001). CNS and Staphylococcus aureus cultures were predominantly sensitive to linezolid, teicoplanin, tigecycline, vancomycin, and mupirocin. Conjunctival normalization times were similar between the three groups (p>0.05). Anatomical and functional success rates were not found to be significantly correlated with preoperative conjunctival and lacrimal sac culture positivity (p>0.05). Conclusions: Similar rates of preoperative and 1-week postoperative conjunctival culture positivity were observed in all the groups; a significantly lower bacterial growth rate was observed in postoperative conjunctival cultures. CNS was the most commonly isolated organism. Bacterial growth rates in the lacrimal sac samples were significantly higher in the EN-DCR group. Bacterial growth rates obtained preoperatively from the conjunctival and lacrimal sac culture samples were not correlated with DCR success.

RESUMO Objetivo: Comparar a flora conjuntival, do saco lacrimal e nasal com o tempo de normalização após dacriocistorrinostomia (DCR) externa (EX-), endoscópica (EN-) e transcanalicular a laser de multi diodo (TC-) para correlacionar a positividade da cultura com o sucesso cirúrgico, assim como identificar a sensibilidade aos antibióticos em amostras de saco lacrimal. Métodos: Neste estudo prospectivo, 90 pacientes com obstrução do canal nasolacrimal adquirida primária foram incluídos e divididos em grupos EX-DCR (n=32), EN-DCR (n=28) e TC-DCR (n=30). Culturas e antibiogramas conjuntivais, nasais e do saco lacrimal foram analisados. Resultados: Staphylococcus coagulase-negativo (CNS) foi o organismo predominante isolado no pré-operatório (conjuntiva e nariz), no transoperatório (saco lacrimal) e pós-operatório (conjuntiva), nos 3 grupos. Taxas de positividade de cultura da conjuntiva pré- e pós-operatórias nos três grupos foram semelhantes (p>0,05). A diferença nas taxas de crescimento do saco lacrimal dos três grupos foi estatisticamente significativa (p=0,001). CNS e S. aureus foram mais sensíveis a linezolida, teicoplanina, a tigeciclina, vancomicina e mupirocina. O tempo de normalização conjuntival foi semelhante nos três grupos (p>0,05). Não houve relação estatisticamente significativa entre as taxas de sucesso anatômicas e funcionais e a positividade da cultura conjuntival e de saco lacrimal pré-operatória (p>0,05). Conclusões: Pacientes submetidos a EX-DCR, EN-DCR, e TC-DCR apresentaram positividades de cultura conjuntival semelhantes no pré-operatório e na 1a semana pós-operatória. Houve uma redução significativa na taxa de crescimento das culturas da conjuntiva pós-operatórias. O organismo mais comumente isolado foi o CNS. A taxa de crescimento de bactérias a partir do saco lacrimal foi significativamente maior no grupo PT-DCR. O crescimento bacteriano da conjuntiva no pré-operatório e de amostras do saco lacrimal no transoperatório não se relacionaram com o sucesso da DCR.

In vivo performance of different scaffolds for dental pulp stem cells induced for odontogenic differentiation

Abstract This study was designed to determine the in vivo performance of three different materials as scaffolds for dental pulp stem cells (DPSC) undergoing induced odontogenic differentiation. An odontogenic medium modified by the addition of recombinant human bone morphogenetic protein 2 was used in the experimental groups to induce differentiation. Mesenchymal stem cell medium was used in the control groups. DPSC were transplanted onto the backs of mice via three scaffolds: copolymer of L-lactide and DL-lactide (PLDL), copolymer of DL-lactide (PDL) and hydroxyapatite tricalcium phosphate (HA/TCP). The expression levels of dentin sialo-phosphoprotein (DSPP), dentin matrix protein-1 (DMP1), enamelysin/matrix metalloproteinase 20 (MMP20) and phosphate-regulating gene with homologies to endopeptidases on X chromosome (PHEX) were analysed using RT-PCR. The expressions in the experimental groups were compared to those in the control groups. The transcript expressions at 6 and 12 weeks were significantly different for all scaffolds (p < 0.05), except for the expression of DSPP in the PLDL group with regard to the time variable. Although there was a decrease in the expression of enamelysin/MMP20 in PLDL and HA/TCP at 12 weeks, all other expressions increased and reached their highest level at 12 weeks. The highest DSPP expression was in the PDL group (p < 0.05). The highest expression of DMP1 was detected in the HA/TCP group (p < 0.05). The highest expression of PHEX was in the PLDL group (p < 0.05). Consequently, PLDL and PDL seemed to be promising scaffold candidates for odontogenic regeneration at least as HA-TCP, when they were applied with the DPSC induced for odontogenic differentiation.