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(1) Background: recent evidence suggests that long low-dose capecitabine regimens have a synergistic effect with endocrine therapy as aromatase inhibitors (AIs), and might increase overall survival for hormone-receptor-positive, HER2-negative, metastatic breast cancer compared to both treatments. We performed a retrospective study to confirm the efficacy and expand the safety data for capecitabine plus AI (a combination henceforth named XELIA) for this indication. (2) We conducted a single-center retrospective cohort study of 163 hormone receptor-positive metastatic breast cancer patients who received either the XELIA regimen, capecitabine, or an aromatase inhibitor (AI) as single agents in first-line treatment. The primary endpoint was progression-free survival, and the secondary endpoints were overall survival, best objective response, and toxicity incidence. (3) Results: the median progression-free survival for patients receiving XELIA, AI, and capecitabine was 29.37 months (20.91 to 37.84; 95% CI), 20.04 months (7.29 to 32.80; 95% CI) and 10.48 (8.69 to 12.28; 95% CI), respectively. The overall response rate was higher in the XELIA group (29.5%) than in the AI (14.3%) and capecitabine (9.1%) groups. However, the differences in overall survival were not statistically significant. Apart from hand-foot syndrome, there were no statistically significant differences in adverse events between the groups. (4) Conclusions: this retrospective study suggests that progression-free survival and overall response rates improved with the XELIA regimen compared to use of aromatase inhibitors and capecitabine alone. Combined use demonstrated an adequate safety profile and might represent an advantageous treatment in places where CDK 4/6 is not available. Larger studies and randomized clinical trials are required to confirm the effects shown in our study.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Capecitabina/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Estudos Retrospectivos , Receptor ErbB-2 , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMO
Babesia bovis, a tick-transmitted apicomplexan protozoon, infects cattle in tropical and subtropical regions around the world. In the apicomplexans Toxoplasma gondii and Plasmodium falciparum, rhomboid serine protease 4 (ROM4) fulfills an essential role in host cell invasion. We thus investigated B. bovis ROM4 coding genes; their genomic organization; their expression in in vitro cultured asexual (AS) and sexual stages (SS); and strain polymorphisms. B. bovis contains five rom4 paralogous genes in chromosome 2, which we have named rom4.1, 4.2, 4.3, 4.4 and 4.5. There are moderate degrees of sequence identity between them, except for rom4.3 and 4.4, which are almost identical. RT-qPCR analysis showed that rom4.1 and rom4.3/4.4, respectively, display 18-fold and 218-fold significantly higher (p < 0.01) levels of transcription in SS than in AS, suggesting a role in gametogenesis-related processes. In contrast, transcription of rom4.4 and 4.5 differed non-significantly between the stages. ROM4 polymorphisms among geographic isolates were essentially restricted to the number of tandem repeats of a 29-amino acid sequence in ROM4.5. This sequence repeat is highly conserved and predicted as antigenic. B. bovis ROMs likely participate in relevant host−pathogen interactions and are possibly useful targets for the development of new control strategies against this pathogen.
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Babesia bovis and B. bigemina are tick-transmitted parasites causing bovine babesiosis, characterized by significant morbidity and mortality leading to economic losses to the livestock industry in tropical and subtropical regions worldwide. Animals that recover from acute infection remain carriers with low parasitemia acting as a source of transmission, and often escape detection. An improved diagnosis of a B. bovis and/or B. bigemina infection of carrier animals is enabled by the availability of detection methods with high sensitivity. To this end, two nested PCR assays targeting the cytochrome b (cytb) genes of B. bovis and B. bigemina (cytb-nPCR), have been recently developed and an increased sensitivity with respect to reference protocols has been shown (Romero-Salas et al., 2016). In this study, the specificity against a panel of hemoparasites that potentially co-occur with B. bovis and B. bigemina was demonstrated to ensure applicability of the cytb-nPCR assays in a wide range of regions where bovine babesiosis is endemic. Furthermore, we compared both reported cytb-nPCR assays with reference nPCR and qPCR protocols for (i) their capability to detect carrier animals in the field, and (ii) their reproducibility when performed in different laboratories by independent operators. We show that, in a panel of bovine field samples (n = 100), the cytb-nPCR assays detected a considerably higher number of 25% B. bovis and 61% B. bigemina-positive animals compared to 7% and 20% B. bovis and 55% and 49% B. bigemina-positive animals when tested by reference nPCR and qPCR protocols, respectively. Cytb-nPCRs were also found superior in the detection of carrier animals when field samples from Africa were analyzed. In addition, both the B. bovis and B. bigemina cytb-nPCR assays were independently validated in a single blinded study in three laboratories. Importantly, no significant differences in the number/percentage of infected animals was observed using cytb-nPCR assays. In summary, the cytb-nPCR assays detected a considerably higher number of chronically infected B. bovis and B. bigemina carrier animals compared to reference nPCR and qPCR protocols, when applied in different epidemiological field situations. Furthermore, a high reproducibility between laboratories could be demonstrated.
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Babesia bovis , Babesia , Babesiose , Doenças dos Bovinos , Carrapatos , Animais , Babesia/genética , Babesia bovis/genética , Babesiose/parasitologia , Bovinos , Doenças dos Bovinos/parasitologia , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Reprodutibilidade dos Testes , Carrapatos/genéticaRESUMO
PURPOSE: Pregnancy-associated breast cancer (PABC) poses a clinical challenge and its prognosis remains controversial. During the pregnancy and postpartum periods, the breast undergoes biological events that may uniquely influence disease behavior and treatment response. This study aimed to assess if a PABC diagnosis influences survival compared to non-PABC. METHODS: A single-center record review was performed to identify PABC patients diagnosed from January 2007 through June 2018. Two controls were matched to each PABC case by stage, immunohistochemical (IHC) subtype, age (± 3) and year of diagnosis (± 2). Disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared with the log-rank test. Multivariate analysis was used to assess the impact of PABC on outcomes. RESULTS: 125 PABC patients (pregnant: 62; postpartum: 63) and 250 controls were included. Median follow-up was 67.7 and 73.4 months, respectively. 4-year DFS was 62% in pregnant vs 78% in controls (p = 0.010), and 63% in postpartum vs 83% in controls (p = 0.034). Subanalysis by IHC subtype revealed a significantly inferior DFS in PABC with hormone receptor-positive/HER2-negative (p = 0.032) and HER2-positive disease (p = 0.005) compared to corresponding non-PABC patients. 4-year OS was similar between case groups and controls. Multivariate analysis supported the independent impact of pregnant and postpartum status on DFS (p < 0.05). CONCLUSION: Patients diagnosed during pregnancy and early postpartum are at high risk of recurrence. Further research is warranted to better characterize PABC tumor biology and enable the identification of novel therapeutic interventions to improve treatment outcomes.
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Neoplasias da Mama , Complicações Neoplásicas na Gravidez , Neoplasias da Mama/diagnóstico , Estudos de Casos e Controles , Feminino , Humanos , Recidiva Local de Neoplasia , Período Pós-Parto , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , PrognósticoRESUMO
Bovine babesiosis is a tick-transmitted haemoparasitic disease caused by Babesia bovis and B. bigemina affecting cattle of tropical and subtropical regions around the world. Pathogens are transmitted by the tick vector Rhipicephalus microplus displaying a widespread distribution in northeastern Argentina. The disease is characterized by significant animal morbidity and mortality resulting in considerable economic loss. In this study, B. bovis and B. bigemina infection was investigated in a cattle herd of 150 adult bovines of pure Braford breed raised in a tick-hyperendemic field using molecular and serum antibody tests. A highly sensitive nested polymerase chain reaction (nPCR) assay targeting a species-specific region of the apocytochrome b gene resulted in direct B. bovis and B. bigemina detection in 27.3% and 54.7% of bovines, respectively. A recently developed immunochromatographic strip test (ICT) based on recombinant forms of spherical body protein 4 and the C-terminal region of rhoptry-associated protein 1 showed that 71.3% and 89.3% of bovines were seropositive for B. bovis and B. bigemina, respectively. The mixed infection rate as observed by direct (19.3%) and indirect detection (65.3%) coincided with those expected, respectively. Importantly, four months after sampling, nine bovines of the studied herd showed clinical signs of bovine babesiosis of which six animals eventually died. Microscopic detection of infected erythrocytes in Giemsa-stained blood smears confirmed B. bovis infection. Our study demonstrates that although animals showed a relatively high and very high rate of immunity against infection with B. bovis (71.3%) and B. bigemina (89.3%) parasites, respectively, clinical cases and fatalities due to the infection with B. bovis were observed. It is proposed that the most adequate control measure in the studied epidemiological situation is to vaccinate animals to prevent losses and/or an outbreak of bovine babesiosis.
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Babesia/isolamento & purificação , Babesiose/epidemiologia , Doenças dos Bovinos/epidemiologia , Rhipicephalus/parasitologia , Animais , Argentina/epidemiologia , Babesia/genética , Babesia/imunologia , Babesia bovis/genética , Babesia bovis/imunologia , Babesia bovis/isolamento & purificação , Babesiose/parasitologia , Bovinos , Doenças dos Bovinos/parasitologia , Cromatografia de Afinidade/veterinária , Feminino , Masculino , Reação em Cadeia da Polimerase/veterinária , Sensibilidade e Especificidade , Especificidade da EspécieRESUMO
INTRODUCTION: Assessment of acute postoperative pain is mandatory for effective treatments. Pain trajectories may help professionals improve treatments. It has been suggested that uncontrolled pain in the immediate postoperative period generates higher pain intensities on the following days of hospital stay. OBJECTIVE: To determine the relationship between pain during the first postoperative hour and the first 24 postoperative hours. METHODS: Setting: a general university hospital. Study design: a prospective observational, analytical study of patients undergoing surgical procedures under general anesthesia and hospitalized for at least 24 hours. Five assessments of pain were carried out during the first hour in the recovery room followed by three assessments during the first 24 hours. The slopes of pain trajectories were calculated, and the relationship between them was analyzed. RESULTS: 234 patients were recruited, 31.3% had uncontrolled pain on arrival at the recovery room; at the end of the first 24 hours after surgery, 5.5% of the patients had uncontrolled pain. The first pain intensity score in the recovery room correlated negatively with the slope for the first hour (P1): rS = -0.657 (p = 0.000). Similarly, the first pain intensity score had a negative association with the pain trajectory slope during the hospital stay (P2): rS = -0.141 (p = 0.032). When comparing the two slopes, a nonsignificant negative correlation was found: rS = -0.126. CONCLUSIONS: the trajectory of pain during the first hour does not predict the behavior of the trajectory during the first day after surgery.
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Dor Aguda/fisiopatologia , Dor Pós-Operatória/fisiopatologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Distribuição por Sexo , Fatores de Tempo , Adulto JovemRESUMO
SUMMARY INTRODUCTION: Assessment of acute postoperative pain is mandatory for effective treatments. Pain trajectories may help professionals improve treatments. It has been suggested that uncontrolled pain in the immediate postoperative period generates higher pain intensities on the following days of hospital stay. OBJECTIVE: To determine the relationship between pain during the first postoperative hour and the first 24 postoperative hours. METHODS: Setting: a general university hospital. Study design: a prospective observational, analytical study of patients undergoing surgical procedures under general anesthesia and hospitalized for at least 24 hours. Five assessments of pain were carried out during the first hour in the recovery room followed by three assessments during the first 24 hours. The slopes of pain trajectories were calculated, and the relationship between them was analyzed. RESULTS: 234 patients were recruited, 31.3% had uncontrolled pain on arrival at the recovery room; at the end of the first 24 hours after surgery, 5.5% of the patients had uncontrolled pain. The first pain intensity score in the recovery room correlated negatively with the slope for the first hour (P1): rS = −0.657 (p = 0.000). Similarly, the first pain intensity score had a negative association with the pain trajectory slope during the hospital stay (P2): rS = −0.141 (p = 0.032). When comparing the two slopes, a nonsignificant negative correlation was found: rS = −0.126. CONCLUSIONS: the trajectory of pain during the first hour does not predict the behavior of the trajectory during the first day after surgery.
RESUMO INTRODUÇÃO: A avaliação da dor pós-operatória aguda é obrigatória para tratamentos eficientes. As trajetórias da dor podem ajudar os profissionais a melhorar os tratamentos. Tem sido sugerido que a falta de controle da dor no período pós-operatório imediato vai gerar maior intensidade dessa dor durante os dias seguintes de estadia no hospital. OBJETIVO: Determinar o relacionamento entre a dor durante a primeira hora pós-operatória e as 24 horas após a mesma. MÉTODOS: Lugar da pesquisa: Hospital universitário geral. Desenho do estudo: Foi feito um estudo analítico prospectivo operacional com pacientes submetidos a procedimentos cirúrgicos sob anestesia geral e que foram hospitalizados pelo menos 24 horas antes. Cinco avaliações de dor foram feitas na primeira hora na sala de recuperação, seguidas de três avaliações durante as primeiras 24 horas. Os declives das trajetórias da dor foram calculados e seu relacionamento entre elas foi analisado. RESULTADOS: Duzentos e trinta e quatro pacientes foram recrutados, 31,3% apresentaram dor não controlada no ingresso à sala de recuperação; no final das primeiras 24 horas após a cirurgia, 5,5% dos pacientes apresentaram dor não controlada. O score da primeira intensidade de dor na sala de recuperação teve uma correlação negativa com o declive da primeira hora (P1): rS = −0,657 (p=0,000). De maneira similar, o score na primeira intensidade de dor teve uma associação negativa com o declive da trajetória da dor durante a permanência no hospital (P2): rS = −0,141 (p=0,032). Quando comparados os dois declives, não foi encontrada uma correlação significativa: rS = −0,126. CONCLUSÃO: A trajetória da dor durante a primeira hora não prediz o comportamento da trajetória durante o primeiro dia após a cirurgia.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Dor Pós-Operatória/fisiopatologia , Dor Aguda/fisiopatologia , Fatores de Tempo , Medição da Dor , Estudos Prospectivos , Distribuição por Sexo , Distribuição por Idade , Tempo de Internação , Pessoa de Meia-IdadeRESUMO
Water buffaloes (Bubalus bubalis) are raised in tropical and subtropical regions of the world, and act as hosts of Babesia bovis parasites and the tick vector Rhipicephalus microplus. As no clinical cases of B. bovis-infection have been reported, we hypothesized that, unlike bovines, water buffaloes respond asymptomatically to an acute infection. To test this hypothesis, we inoculated two groups of 24-month-old Mediterranean breed water buffaloes with 108 erythrocytes infected with two Argentine B. bovis isolates: BboM2P (nâ¯=â¯5) or BboS2P (nâ¯=â¯5). These strains displayed mild (BboM2P) or high (BboS2P) pathogenicity in Bos taurus calves of the same age (nâ¯=â¯5 and nâ¯=â¯1, respectively), when tested in parallel. In water buffaloes, no changes in body temperature were observed with both strains, and no hematocrit changes were detected in BboM2P-inoculated animals. In contrast, in the BboS2P-inoculated water buffalo group significant but relatively minor reductions in haematocrit values were noted compared to the infected bovine. The parasitemia attained in water buffaloes was considerably lower than in bovines and could only be detected by nested PCR, or indirectly via serology, whereas in most bovines, it could also be detected in Giemsa-stained smears under the light microscope. Our results show that water buffaloes present no or significantly mitigated clinical symptoms to B. bovis infections and suggest that they are able to substantially reduce and/or eliminate B. bovis parasites from circulation by an efficient innate immune mechanism.
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Babesia bovis/isolamento & purificação , Babesiose/parasitologia , Doenças dos Bovinos/diagnóstico , Parasitemia/diagnóstico , Animais , Babesia bovis/genética , Babesia bovis/imunologia , Babesia bovis/patogenicidade , Babesiose/diagnóstico , Babesiose/imunologia , Búfalos/imunologia , Búfalos/parasitologia , Bovinos , Doenças dos Bovinos/sangue , Doenças dos Bovinos/parasitologia , DNA de Protozoário/genética , Ensaio de Imunoadsorção Enzimática/veterinária , Eritrócitos/parasitologia , Hematócrito , Imunidade Inata , Masculino , Parasitemia/epidemiologia , Reação em Cadeia da Polimerase/veterinária , Rhipicephalus/microbiologia , Testes SorológicosRESUMO
BACKGROUND: Mask ventilation is routinely performed during anesthesia. Under some circumstances, it might be difficult to perform, such as in edentulous patients, due to inadequate mask seal. We developed a new device called NIPARA and studied its use For ventilation optimization in edentulous patients. METHODS: This randomized controlled trial included edentulous adults who had no other predictors of difficult airway, scheduled to undergo general anesthesia. Patients were assigned either to the NIPARA device group or to the control group (oral airway only). The primary outcomes were peak inspiratory pressure and tidal volume values of the first 14 breaths. The secondary outcome was the incidence of complications. RESULTS: Data from 37 patients were collected during a one-year period (twenty in the NIPARA device group and 17 in the control group). The difference in mean PIP was not statistically significant. The tidal volume was 1.5 times greater in the NIPARA group than in the control group. One patient from the intervention group had minimal oral trauma. CONCLUSION: In the administration of face mask ventilation, NIPARA is an effective device that significantly improves the tidal volume administered in edentulous patients.