Use of interval-censored survival data as an alternative to Kaplan-Meier survival curves: studies of oral lesion occurrence in liver transplants and cancer recurrence

After undergoing liver transplantation, children are susceptible to oral lesions due to immunosuppressant drugs that are needed to maintain the transplant. In this context, it is important to understand how disease characteristics and age at transplantation influence the development of these lesions. Monitoring of lesions begins after transplantation and children are usually observed by a specialist in stomatology at periodic visits. Consequently, lesion development is estimated to occur between two observed times, and this is characterized as interval-censored data. However, in clinical practice, it is common to assume the moment of observation as the time of event occurrence, thereby excluding interval-censored data. Here, we discuss the impact of excluding interval-censored mechanisms in statistical analyses by using simulation studies to consider differences in sample sizes and amplitudes between observed intervals. Then, application studies are presented which use a data set from a prospective study that was conducted to investigate oral lesions in patients after liver transplantation at the A.C.Camargo Cancer Center in Brazil between 2013 and 2016 and a data set involving recurrent ovarian cancer in patients diagnosed with high-grade serous carcinoma at the A.C.Camargo Cancer Center between 2003 and 2016 (AU)

Incidence and functional outcome of atrial fibrillation and non-atrial fibrillation- related cardioembolic stroke in Joinville, Brazil: a population-based study / Incidência e desfecho funcional de AVC cardioembólico com e sem fibrilação atrial em Joinville, Brazil: estudo de base populacional

ABSTRACT Among ischemic strokes, cardioembolic (CE) stroke has the worst outcome. We measured the incidence of atrial fibrillation (AF) and non-AF related CE strokes, previous anticoagulant use, and the 90-day functional outcome. Using multiple overlapping sources, we included all CE strokes that occurred in 2015 in Joinville, Brazil. Of the 374 ischemic strokes, 23% (84) were CE. The CE age-adjusted incidence, per 1,000 person-years, was 0.14 (0.11–0.17). Of the 26 patients with known prior AF, 73% (19) were not anticoagulated, 77% (20) had a CHA2DS2VASc score ≥ 3 and 81% (21) had a HAS-BLED score < 3. After three months, approximately one third of those 26 patients died or became disabled. The incidence of CE stroke in our sample was lower than in other population-based studies. The opportunity for anticoagulation was missed in one third of cases.

RESUMO Entre todos os subtipos de AVC isquêmico, os eventos cardioembólicos (CE) apresentam os piores prognósticos. Determinamos a incidência de AVC isquêmico CE, associada ou não à fibrilação atrial (FA), o uso prévio de anticoagulantes e os desfechos funcionais em Joinville, Brasil. Utilizando múltiplas e sobrepostas fontes de informação, registramos todos os primeiros eventos CE ocorridos em 2015. Entre 374 eventos isquêmicos, 23% (84) foram CE. A incidência ajustada, para qualquer fonte cardioembólica, foi 0.14 (0.11–0.17) por 1000 pessoas-ano. Entre 26 pacientes com FA previamente conhecida, 73% (19) não estavam anticoagulados, 77% (20) tinham ≥ 3 pontos na escala CHA2DS2VASc e 81 % (21) < 3 pontos na escala HAS-BLED. Após 3 meses, um terço destes 26 pacientes morreram ou ficaram dependentes. A incidência de AVC I CE em Joinville é menor do que em outros estudos de base populacional. Um terço dos casos de AVC I CE com FA previamente conhecida perderam a oportunidade de anticoagulação.

Inflammatory pigment epithelial detachment associated with Blastocystis hominis

Objective@#To describe a case of inflammatory pigment epithelial detachment (PED) presumed to be secondary to the amoeba Blastocystis hominis.@*Methods@#This is an interventional case report.@*Results@#A 46-year-old male complained of visual distortion in the left eye for 7 months. Examination revealed the presence of a subretinal cystic lesion on the fovea. Optical coherence tomography demonstrated a PED with a hyperreflective lesion over the detached retinal pigment epithelium (RPE). Work-up included a fecalysis, which revealed the presence of Blastocystis hominis. The patient was treated with oral metronidazole. RPE detachment resolved after treatment with no recurrence in 30 months of follow-up.@*Conclusion@#Intestinal parasitic infection may be associated with retinal disease and should be included in the differential diagnosis of PED when OCT reveals a hyperreflective lesion.

Capacidade fagocítica de polimorfonucleares (PMN) humanos frente a várias partículas: Candida albicans, Zymosan, Staphylococcus aureus, Micrococcus, Escherichia coli / Phagocytosis capacity of the human neutrophils (PMN) against some particles

O processo de fagocitose envolve a ligação de partículas a receptores de superfície, resultando em indução de sinais intracitoplasmáticos e internalização de partículas, tendo importante papel na evolução das moléstias infecciosas, principalmente das bacterianas. Neste trabalho, nos propusemos a estudar a fagocitose “in vitro”, por meio do isolamento de PMN do sangue periférico de 17 amostras provenientes de doadores do Hemocentro do HURNP colocados em contato com as diversas partículas acima citadas. Com o objetivo de se obter a indicação da partícula mais adequada para uso na rotina laboratorial, as características avaliadas foram a capacidade fagocítica e a facilidade de leitura ao microscópio ótico. Os resultados obtidos indicam maior capacidade fagocítica (em porcentagem de células que apresentaram fagocitose) quando se faz uso da partícula de Zymosan (77 por cento) seguido de C. albicans (70 por cento) e o maior índice de partículas fagocitadas (em porcentagem de células que fagocitaram acima de 4 partículas) quando se fez uso de Zymozan (50 por cento) seguido de S. aureus (37 por cento) permitindo concluir que destas partículas a mais adequada para uso na rotina laboratorial é o Zimosan.

Increased clearance of Candida albicans from the peritoneal cavity of mice pretreated with concanavalin A or jacalin

We have studied the role of polymorphonuclear leukocytes and macrophages in the clearance of Candida albicans from the peritoneal cavity of Swiss mice after treatment with jacalin or concanavalin A (Con-A). Mice (25-30 g, N = 7 per group) received jacalin or Con-A (500 µg/0.5 ml PBS) intraperitoneally 96 h before intraperitoneal inoculation of 5 x 10(7) yast cell. The clearance of Candida from the peritoneal cavity was complete 24 h after inoculation for animals pretreated with jacalin and 48 h after inoculation for animals pretreated with Con-A, whereas a reduction to 4 x 10(4) yeast cells/cavity occurred in control animals 48 h after inoculation. Pretreatment with jacalin or Con-A reduced the recovery of C. albicans from spleen, kidney and liver 10- to 80-fold compared to control animals. Pretreatment with the lectins increased the number of phagocytic cells in the peritoneal exudate 5-to 10-fold and their candidacidal activity was increased 6-fold compared to controls. These data explain the increased rate of clearance and reduced yeast dissemination to the viscera of lectintreated mice

Evidence for the participation of proteinases released by Candida albicans in the early killing of peritoneal macrophages in vitro

We have investigated the possibility that proteinases released by Candida albicans participate in the early killing of three types of mice peritoneal macrophage (resident, thioglycollate-elicited, or Con-A-activated)in vitro. Phagocytic assays were performed by incubation of macrophages and C. albicans together at a 1:10 ratio for 30 min at 37 grade C in RPMI medium buffered to pH 7.0 with 12 mM Hepes without serum. With no albumin added to the medium, the medium, the macrophages were 85% to 100% damaged and unviable, to a greater extent than expected from the proportion of phagocytic cells containing germ tubes. When 10 mg/ml of albumin was added to the medium, however, 90% of the macrophages remained viable for the 2 hours of the phagocytic assay, suggesting that albumin may have acted as a substrate for or inhibitor of proteinases released by C. albicans, thereby protecting the macrophage from the proteolytic action of the proteinases. The phagocytosis of IgG-coacted erythrocytes was reduced to 43% when IgG was preincubated with the supernatant from C. albicans cultures, but the addition of 10 mg/ml albuumin or of 5 ug/ml pepstatin (an inhibitor of C. albicans acid proteinases) to the same supernatans prevented the effect on phagocytosis of IgG-coated erythrocytes. These results suggest that proteinases released from C. albicans are involved in the early killing of macrophages

Phagocytosis of enteropathogenic Escherichia coli and Candida albicans by lectin-like receptors

1. Ingestion of enteropathogenic Escherichia coli or Candida albicans by thioglycollate-elicited macrophages and polymorphonuclear leukocytes was investigated in vitro, 2. Goat antiserum against mannose receptors caused about 50% inhibition of E. coli phagocytosis and about 90% inhibition of C. albicans phagocytosis. 3. E. coli and C. albicans uptake was inhibited by about 60% and 98%, respectively, by plating the macrophages onto substrates coated with poly-L-lysine-mannan. Further addition of 50 mM mannose to the medium significantly increased the inhibition of phagocytosis of E. coli by macrophages from 60.7 +/- 1.5 to 79.8 +/- 13.1 and by polymorphonuclear cells from 58.9 +/- 3.7 to 88.7 +/- 4.9. 4. Preincubation of phagocytic cells with antiserum against substance A of human erythrocytes reduced E. coli ingestion by 95%, but this inhibition was not observed when the antiserum was incubated with N-acetylgalactosamine (50 mM) before being added to the phagocytes. The phagocytosis of C. albicans was not inhibited by anti-substance A antiserum. 5. The phagocytosis of E. coli was inhibited by about 25% by the addition of 7.8 micrograms/ml soluble mannan to the medium, and by about 50% by the addition of 50 mMN-acetylgalactosamine; when both substances were added to the medium, an additive inhibition of about 75% was observed. 6. These results indicate that mannose receptors on the surface of phagocytic cells mediate E. coli or Candida albicans uptake and that the binding of bacteria to N-acetylgalactosamine residues from the membrane of phagocytes is also involved in the phagocytosis of E. coli

Inhibition of macrophage phagocytosis of Escherichia coli by mannose and mannan

1. We investigated the possibility that Candida albicans and Escherichia coli are interiorized by thioglycollate-elicited peritoneal macrophages by interacting with the same receptor. 2. D-mannose (50 mM), a sugar recognized by mannose receptors, reduced the phatfocytosis of C. albicans and E. coli to 46% and 38% of control values, respectively. The presence of 50 mM galactose did not affect the phagocytosis of either microorganism. However, mannan from saccharomyces cerevisiae (0.5 mg/ml) inhibited phagocytosis by 70% for both microorganisms. 3. The ingestion of C. albicans and E. coli was reduced by 85% and 95%, respectively, in the presence of 10 mM EGTA. 4. These results suggest that the mannose receptor, which mediates the recognition of C. albicans by macrophages, might also mediate the phagocytosis of Escherichia coli 0111

Participation of mannose receptors on the surface of stimulated macrophages in the phagocytosis of glutaraldehyde-fixed Candida albicans, in vitro

We have evaluated the participation of mannose receptors on the surface of stimulated macrophages in the phagocytosis of Candida albicans in vitro. A dose-dependent 8.6 to 88.3% reduction of phagocytosis was observed in the presence of 0.5 to 5.0 mg/ml of the mannose-rich glycoprotein invertase (either native or denatured) in the incubation medium. Macrophages plated onto substrates coated with poly-L-lysine-mannan also showed a 99% reduction of phagocytic activity toward Candida albicans, but phagocytosis of IgG-coated erytrocytes was not inhibited under the same conditions. These results indicate that mannose receptors are involved in one of the initial steps of phagocytosis of Candida albicans by macrophages