The Role of Senescent CD8+T Cells in the Pathogenesis of Disseminated Leishmaniasis.

Disseminated leishmaniasis (DL) caused by L. braziliensis is characterized by the presence of 10 to more than 1000 lesions spread on the body. While protection against Leishmania is mediated by macrophages upon activation by IFN-γ produced by CD4+T cells, the pathology of disseminated leishmaniasis (DL) could be mediated by macrophages, NK, and CD8+T cells. Herein, we evaluate the participation of senescent CD8+T cells in the pathogenesis of DL. Methods: Peripheral blood mononuclear cells (PBMCs), biopsies, co-cultures of CD8+T cells with uninfected and infected macrophages (MØ), and PBMC cultures stimulated with soluble L. braziliensis antigen (SLA) for 72 h from patients with cutaneous leishmaniasis (CL) and DL were used to characterize senescent CD8+T cells. Statistical analysis was performed using the Mann-Whitney and Kruskal-Wallis tests, followed by Dunn's. Results: Patients with DL have an increase in the frequency of circulating CD8+T cells that present a memory/senescent phenotype, while lesions from DL patients have an increase in the frequency of infiltrating CD8+T cells with a senescent/degranulation phenotype. In addition, after specific stimuli, DL patients' circulating CD8+T with memory/senescent profile, showing degranulation characteristics, increased upon SLA stimuli, and those specific CD8+T cells from DL patients had an increased degranulation phenotype, causing more apoptosis of infected target cells. Conclusions: DL patients show a higher frequency of cytotoxic senescent CD8+T cells compared to CL patients, and that could promote the lysis of infected cells, although without parasite killing, releasing Leishmania to the extracellular compartment, contributing to the spread of parasites.

Leishmania braziliensis exosomes activate human macrophages to produce proinflammatory mediators.

Exosomes, organelles measuring 30-200nm, are secreted by various cell types. Leishmania exosomes consist of many proteins, including heat shock proteins, annexins, Glycoprotein 63, proteins exerting signaling activity and those containing mRNA and miRNA. Studies have demonstrated that Leishmania donovani exosomes downregulate IFN-γ and inhibit the expression of microbicidal molecules, such as TNF and nitric oxide, thus creating a microenvironment favoring parasite proliferation. Despite lacking immunological memory, data in the literature suggest that, following initial stimulation, mononuclear phagocytes may become "trained" to respond more effectively to subsequent stimuli. Here we characterized the effects of macrophage sensitization using L. braziliensis exosomes prior to infection by the same pathogen. Human macrophages were stimulated with L. braziliensis exosomes and then infected with L. braziliensis. Higher levels of IL-1ß and IL-6 were detected in cultures sensitized prior to infection compared to unstimulated infected cells. Moreover, stimulation with L. braziliensis exosomes induced macrophage production of IL-1ß, IL-6, IL-10 and TNF. Inhibition of exosome secretion by L. braziliensis prior to macrophage infection reduced cytokine production and produced lower infection rates than untreated infected cells. Exosome stimulation also induced the consumption/regulation of NLRP3 inflammasome components in macrophages, while the blockade of NLRP3 resulted in lower levels of IL-6 and IL-1ß. Our results suggest that L. braziliensis exosomes stimulate macrophages, leading to an exacerbated inflammatory state that may be NLRP3-dependent.

Prostaglandin E2 contributes to L. braziliensis survival and therapeutic failure in cutaneous leishmaniasis.

Patients with cutaneous leishmaniasis (CL) present an exacerbated inflammatory response associated with tissue damage and ulcer development. In recent years, higher rates of failure to pentavalent antimoniate therapy have been observed, yet the underlying reason remains poorly understood. We hypothesize that the eicosanoid PGE2 favours the establishment of infection by L. braziliensis, which contributes to therapeutic failure. The aim of the present study was to investigate the influence of PGE2 on the survival of L. braziliensis in macrophages and rates of therapeutic failure in CL patients. PGE2, an eicosanoid derived from the metabolism of arachidonic acid by the COX-2 enzyme, plays several roles in immune response. We found that increased PGE2 decreases the microbicidal function of macrophages and is associated with disease severity and therapeutic failure. Additionally, the neutralization of COX-2 by NS398, a selective NSAID, increases the ability of macrophages to kill L. braziliensis and protects against the pathological inflammatory response. Our data suggest that NS398 may serve as an adjunct treatment for CL patients.

Multiple Bilateral Retinal Pigment Epithelial Detachments in a Patient with Systemic Lupus Erythematosus: A Case Report.

Purpose: To report a case of multiple bilateral retinal pigment epithelial detachments (PEDs) in a woman with systemic lupus erythematosus (SLE). Methods: Case Report. Results: A 28-year-old female with mild blurred bilateral vision in both eyes (OU) without pain or any other symptom was admitted to the hospital due to worsening renal function and uncontrolled high blood pressure (HBP). Best-corrected visual acuity (BCVA) was 20/30 and 20/40, right and left eyes, respectively. She had SLE, glucose-6-phosphate dehydrogenase deficiency, and immune thrombocytopenic purpura. BP was over 150/90 mmHg for more than 1.5 years, and she used corticosteroids at varying doses for more than 4 years. During hospitalization, she was taking prednisone 60 mg daily as Class IV lupus nephritis was diagnosed. On fundoscopy, she had a lacy retinal pattern, remarkably on the macula in OU. Spectral-domain optical coherence tomography revealed multiple bilateral serous PEDs and pachychoroid. Angiofluoresceinography displayed multiple pooling hyperfluorescence areas. Six months afterward, while she was on prednisolone 10 mg daily, and antihypertensive medications, BCVA was improved to 20/25 OU. Nevertheless, she had no retinal or choroidal changes. Her findings could be related to SLE choroidopathy, central serous chorioretinopathy-like disease, and/or hypertensive choroidopathy. Conclusions: Ocular involvement affects nearly one-third of SLE patients. The findings are variable and can include nearly any part of the eyeball. Multiple bilateral PEDs have been described in the literature; however, in this case, it is probably multifactorial and not only related to SLE.

Association between axial length and level of education in elderly patients with cataracts unexposed to electronic devices in the first two decades of life / Associação entre diâmetro axial e nível educacional em pacientes idosos com catarata não expostos a dispositivos eletrônicos nas duas primeiras décadas de vida

ABSTRACT Purpose: To determine whether the axial length is associated with the education level in elderly patients with cataracts who were not exposed to electronic devices in the first two decades of life. Methods: This cross-sectional study was conducted in elderly patients with cataracts in Campinas, Brazil. Patients were divided into 2 groups: Group 1 included those who completed, at most, elementary school (including the illiterate and those who partially or totally attended elementary school), which corresponded to 12 years of schooling; Group 2 included, at least, high school graduates (including those who completed high school and those who partially or fully attended university). The sample was selected randomly with stratification for sex and age. The main outcome was the axial length. Results: The sample consisted of 472 elderly patients (236 per group) who underwent cataract surgery. There were 272 (57.6%) men and 200 (42.4%) women; the distribution was symmetrical between the two groups. The median age (IQR; range) was 66 (12; 50-89) years. The median axial length (IQR; range) was 22.82 (1.51; 20.34-28.71) mm in Group 1 and 23.32 (1.45; 20.51-31.34) mm in Group 2 (p<0.001). Conclusion: A greater axial length was associated with a higher level of education in elderly patients with cataracts, suggesting that myopization is related to an increase in activities requiring near-vision even before exposure to electronic devices.

RESUMO Objetivo: Determinar se o diâmetro axial está asso­ciado ao nível educacional em pacientes idosos com catarata que não foram expostos a dispositivos eletrônicos nas duas primeiras décadas de vida. Métodos: Este estudo transversal foi conduzido em pacientes idosos com catarata na cidade de Campinas, Brasil. Os Pacientes foram divididos em 2 grupos: no Grupo 1 foram incluídos aqueles que completaram, pelo menos, o ensino fundamental (incluindo analfabetos e aqueles com ensino fundamental completo ou incompleto), o que corresponde a 12 anos de escolaridade; no Grupo 2 foram incluídos indivíduos que, pelo menos, estudaram até o ensino médio (incluindo indivíduos com ensino médio completo e superior completo ou superior incompleto). A amostra foi selecionada aleatoriamente com estratificação por sexo e idade. O desfecho principal foi a medida do diâmetro axial. Resultados: A amostra foi constituída por 472 indivíduos que foram submetidos a cirurgia de catarata. Duzentos e trinta e seis indivíduos (50%) foram alocados no Grupo 1 e duzentos e trinta e seis indivíduos (50%) no Grupo 2. A mediana da idade (IIQ; intervalo) foi 66 (12; 50-89) anos. Duzentos e setenta e dois (57,6%) eram homens e duzentos (42,4%) mulheres, com distribuição simétrica entre os dois grupos. A mediana do diâmetro axial (IIQ; intervalo) foi 22,82 (1,51; 20,34-28,71) mm no Grupo 1 e 23,32 (1,45; 20,51-31,34) mm no Grupo 2 (p<0,001). Conclusão: Maiores medidas de diâmetro axial foram asso­ciadas a níveis educacionais mais elevados em pacientes idosos submetidos a cirurgia de catarata. Tal achado sugere que a miopização relacionada ao aumento de atividades que utilizam a visão de perto é fenômeno que ocorre antes mesmo da exposição a dispositivos eletrônicos.

Proteinuria in early referral to spectral domain optical coherence tomography for macular edema detection in type 2 diabetes individuals: results from the Brazilian diabetes study.

BACKGROUND: Measurement of retinal thickness by optical coherence tomography (OCT) shows higher diagnostic accuracy for diabetic macular edema (DME) than fundus photography alone. The expanding gap between the rising number of type 2 diabetes (T2D) individuals and the availability of OCT devices demands a targeted selection of individuals at higher risk of DME who would benefit the most from early referral. We sought to appraise if proteinuria should be considered in a targeted referral of T2D individuals to OCT examination. METHODS: This study was a cross-sectional analysis of 576 consecutive patients enrolled in the Brazilian Diabetes Study between June/2016 and December/2021 who underwent OCT exam and urinalysis to assess ME and proteinuria status, respectively. Differences in the prevalence of DME between proteinuria groups and across a range of diabetic retinopathy (DR) stages were evaluated. RESULTS: Among 1134 eyes included in this analysis, the prevalence of proteinuria was 22% and 18.2% of eyes had DME. Proteinuria was related to an increased prevalence of DME (13.2% vs 38.7% for control vs proteinuria, respectively; p < .001), with an OR of 4.08 [95% confidence interval (CI): 2.50-6.64, p < .001), after adjustment for covariates. Proteinuria was independently related to DME also among eyes with non-apparent DR [OR: 2.82; 95%CI: 1.34-5.93; p = .003] and non-proliferative DR (OR of 5.94, 95%CI 2.13-16.62, p < .001). Fundus photography spotted only half of the DME cases detected by OCT. CONCLUSION: In T2D individuals, early referral to OCT examination should be pursued for all individuals with concurrent proteinuria. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04949152.

TNF-induced metalloproteinase-9 production is associated with neurological manifestations in HTLV-1-infected individuals.

HTLV-1-infected individuals may develop a neurologic inflammatory condition known as HTLV-1-associated myelopathy (HAM/TSP), in which the high production of TNF is observed. These patients exhibit higher proviral loads, enhanced production of proinflammatory cytokines and lymphocyte proliferation in comparison to asymptomatic HTLV-1 carriers and those presenting overactive bladder (OAB-HTLV-infected). Metalloproteinases (MMPs) are known to degrade the components of the blood-brain barrier, favoring the migration of infected cells into the central nervous system. Moreover, the unbalanced production of MMPs and their inhibitors (TIMPs) has also been associated with tissue damage. The present work studied the production of MMP-9 and TIMPs in HTLV-1-infected individuals with and without neurological manifestations. HAM/TSP patients presented higher concentrations of MMP-9 in peripheral blood mononuclear cell (PBMC) culture supernatants, as well as a higher MMP-9/TIMP-3 ratio when compared to the other groups studied. MMP-9 levels positively correlated with proviral load and TNF in OAB-HTLV-infected individuals, and the in vitro neutralization of TNF significantly decreased MMP-9 levels in PBMC culture supernatants. Our findings indicate an association between MMP-9 production and the proinflammatory state associated with HTLV-1 infection, as well as HAM/TSP.

Pioglitazone, a Peroxisome Proliferator-Activated Receptor-γ Agonist, Downregulates the Inflammatory Response in Cutaneous Leishmaniasis Patients Without Interfering in Leishmania braziliensis Killing by Monocytes.

Patients with cutaneous leishmaniasis (CL) due to Leishmania braziliensis infection have an exacerbated inflammatory response associated with tissue damage and ulcer development. An increase in the rate of patients who fail therapy with pentavalent antimony has been documented. An adjuvant therapy with an anti-inflammatory drug with the potential of Leishmania killing would benefit CL patients. The aim of the present study was to investigate the contribution of peroxisome proliferator-activated receptor-γ (PPAR-γ) activation by pioglitazone in the regulation of the inflammatory response and L. braziliensis killing by monocytes. Pioglitazone is an oral drug used in the treatment of diabetes, and its main mechanism of action is through the activation of PPAR-γ, which is expressed in many cell types of the immune response. We found that activation of PPAR-γ by pioglitazone decreases the inflammatory response in CL patients without affecting L. braziliensis killing by monocytes. Our data suggest that pioglitazone may serve as an adjunctive treatment for CL caused by L. braziliensis.

Association between axial length and level of education in elderly patients with cataracts unexposed to electronic devices in the first two decades of life.

PURPOSE: To determine whether the axial length is associated with the education level in elderly patients with cataracts who were not exposed to electronic devices in the first two decades of life. METHODS: This cross-sectional study was conducted in elderly patients with cataracts in Campinas, Brazil. Patients were divided into 2 groups: Group 1 included those who completed, at most, elementary school (including the illiterate and those who partially or totally attended elementary school), which corresponded to 12 years of schooling; Group 2 included, at least, high school graduates (including those who completed high school and those who partially or fully attended university). The sample was selected randomly with stratification for sex and age. The main outcome was the axial length. RESULTS: The sample consisted of 472 elderly patients (236 per group) who underwent cataract surgery. There were 272 (57.6%) men and 200 (42.4%) women; the distribution was symmetrical between the two groups. The median age (IQR; range) was 66 (12; 50-89) years. The median axial length (IQR; range) was 22.82 (1.51; 20.34-28.71) mm in Group 1 and 23.32 (1.45; 20.51-31.34) mm in Group 2 (p<0.001). CONCLUSION: A greater axial length was associated with a higher level of education in elderly patients with cataracts, suggesting that myopization is related to an increase in activities requiring near-vision even before exposure to electronic devices.

The Influence of Infection by Different Leishmania (Viannia) braziliensis Isolates on the Pathogenesis of Disseminated Leishmaniasis.

Disseminated Leishmaniasis (DL) is an emerging and severe form of Leishmania (Viannia) braziliensis infection defined by the presence of 10 and up to more than 1,000 skin lesions. The mechanisms underlying parasite dissemination remain unknown. Genotypic differences among species of L. braziliensis have been associated with different clinical forms of disease. The present work compared the function of monocytes obtained from patients with cutaneous leishmaniasis (CL) and DL in response to infection with L. braziliensis isolates of both these two clinical forms of disease. Mononuclear cells obtained from DL and CL patients were infected with different L. braziliensis isolates, and numbers of infected cells, parasite load, respiratory burst, TLR2 and TLR4 expression and cytokine production were evaluated. DL isolates infected more monocytes, induced greater respiratory burst, and more cytokine production compared to isolates from CL patients regardless of the origin of monocytes (DL or CL). However, greater parasite multiplication and higher TLR2 and TLR4 expression were seen in monocytes from DL patients compared to CL following infection with DL isolates. Our results indicate the participation of both parasite genotype and host factors in the pathogenesis of DL.

The Leishmania antigen-specific pro-inflammatory response in cutaneous leishmaniasis is linked to disease progression but not to the therapeutic failure of pentavalent antimonials.

High levels of pro-inflammatory cytokines in cutaneous leishmaniasis patients are associated with tissue damage and ulcer development. We found higher levels of TNF and IL-1ß in peripheral blood mononuclear cell supernatants in response to soluble Leishmania antigen in individuals with a longer duration of disease. In addition, Leishmania braziliensis-infected patients with a longer disease progression before treatment presented a shorter time to cure after treatment onset. No associations were found between the levels of the pro-inflammatory cytokines IL-6, TNF and IL-1-ß and patients' response to pentavalent antimony treatment. Our data suggest that while the Leishmania antigen-specific pro-inflammatory cytokines investigated may lead to ulcer development, they do not influence therapeutic failure in cutaneous leishmaniasis patients.

Inhibition of gamma-secretase activity without interfering in Notch signalling decreases inflammatory response in patients with cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) patients present an exacerbated inflammatory response associated with tissue damage and ulcer development. Increasing numbers of patients have exhibited treatment failure, which remains not well understood. We hypothesized that adjuvant anti-inflammatory therapy would benefit CL patients. The aim of the present study was to investigate the contribution of Notch signalling and gamma-secretase activity to the inflammatory response observed in CL patients. Notch signalling is a molecular signalling pathway conserved among animal species. Gamma-secretase forms a complex of proteins that, among other pathways, modulates Notch signalling and immune response. We found that Notch 1 cell receptor signalling protects against the pathologic inflammatory response, and JLK6, a gamma-secretase inhibitor that does not interfere with Notch signalling, was shown to decrease the in-vitro inflammatory response in CL. Our data suggest that JLK6 may serve as an adjuvant treatment for CL patients.

Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature.

Cutaneous leishmaniasis is a localized infection controlled by CD4+ T cells that produce IFN-γ within lesions. Phagocytic cells recruited to lesions, such as monocytes, are then exposed to IFN-γ which triggers their ability to kill the intracellular parasites. Consistent with this, transcriptional analysis of patient lesions identified an interferon stimulated gene (ISG) signature. To determine whether localized L. braziliensis infection triggers a systemic immune response that may influence the disease, we performed RNA sequencing (RNA-seq) on the blood of L. braziliensis-infected patients and healthy controls. Functional enrichment analysis identified an ISG signature as the dominant transcriptional response in the blood of patients. This ISG signature was associated with an increase in monocyte- and macrophage-specific marker genes in the blood and elevated serum levels IFN-γ. A cytotoxicity signature, which is a dominant feature in the lesions, was also observed in the blood and correlated with an increased abundance of cytolytic cells. Thus, two transcriptional signatures present in lesions were found systemically, although with a substantially reduced number of differentially expressed genes (DEGs). Finally, we found that the number of DEGs and ISGs in leishmaniasis was similar to tuberculosis-another localized infection-but significantly less than observed in malaria. In contrast, the cytolytic signature and increased cytolytic cell abundance was not found in tuberculosis or malaria. Our results indicate that systemic signatures can reflect what is occurring in leishmanial lesions. Furthermore, the presence of an ISG signature in blood monocytes and macrophages suggests a mechanism to limit systemic spread of the parasite, as well as enhance parasite control by pre-activating cells prior to lesion entry.

Influence of Obesity on Clinical Manifestations and Response to Therapy in Cutaneous Leishmaniasis Caused by Leishmania braziliensis.

BACKGROUND: Cutaneous leishmaniasis (CL) caused by Leishmania braziliensis is characterized by a single ulcer or multiple cutaneous lesions with raised borders. Cure rates <60% are observed in response to meglumine antimoniate therapy. We investigated the impact of obesity on CL clinical presentation and therapeutic response. METHODS: A total of 90 age-matched patients with CL were included (30 obese, 30 overweight, and 30 with normal body mass index [BMI]). CL was diagnosed through documentation of L. braziliensis DNA by polymerase chain reaction or identification of amastigotes in biopsied skin-lesion samples. Serum cytokine levels were determined by chemiluminescence. Antimony therapy with Glucantime (Sanofi-Aventis; 20 mg/kg/day) was administered for 20 days. RESULTS: Obese CL patients may present hypertrophic ulcers rather than typical oval, ulcerated lesions. A direct correlation between BMI and healing time was noted. After 1 course of antimony, cure was achieved in 73% of patients with normal BMI, 37% of overweight subjects, yet just 18% of obese CL patients (P < .01). Obese CL cases additionally presented higher leptin levels than overweight patients or those with normal BMI (P < .05). CONCLUSIONS: Obesity modifies the clinical presentation of CL and host immune response and is associated with greater failure to therapy.

Macular and choroidal thickness after intracameral moxifloxacin for prevention of postcataract endophthalmitis.

PURPOSE: To determine any changes in macular or choroidal thickness associated with the use of intracameral moxifloxacin as postcataract endophthalmitis prophylaxis. SETTING: University of Campinas, Campinas, São Paulo, Brazil. DESIGN: Prospective, randomized, partially masked, single-site clinical trial. METHODS: Phacoemulsification surgery patients in the experimental group (Group A) received a 0.03 mL intracameral injection of undiluted moxifloxacin from a sealed bottle immediately after phacoemulsification surgery (150 µg in 0.03 mL-Vigamox solution), whereas the control group (Group B) did not. Investigators evaluated in masked fashion macular and choroidal thickness using spectral-domain optical coherence tomography preoperatively and postoperatively. RESULTS: A total of 93 patients were included (48 in Group A and 45 in Group B). Baseline parameters were similar between the groups. Either of the 2 parameters assessed differed statistically between the groups or preoperatively vs postoperatively. On postoperative day 30, central macular thickness was 8.85 ± 14.78 µm in Group A and 10.26 ± 22.44 µm in Group B (P = .7232); choroidal thickness as measured by enhanced depth imaging (EDI) was 1.45 ± 16.13 µm in Group A and 3.74 ± 16.15 in Group B (P = .5017). On postoperative day 60, central macular thickness was 19.53 ± 39.28 µm in Group A and 17.14 ± 53.68 µm in Group B (P = .8363); EDI was 5.08 ± 21.96 µm in Group A and 5.24 ± 15.8 in Group B (P = .9752). CONCLUSIONS: The application of intracameral injection of 0.03 mL of undiluted 0.5% moxifloxacin during phacoemulsification surgery as endophthalmitis prophylaxis induced no changes in macular or choroidal thickness.

Evaluation of the Ability of Miltefosine Associated with Topical GM-CSF in Modulating the Immune Response of Patients with Cutaneous Leishmaniasis.

Cutaneous leishmaniasis (CL) due to L. braziliensis is associated with an exaggerated inflammatory response and tissue damage. Miltefosine is more effective than pentavalent antimony (Sbv) in the treatment of CL, and here, we evaluate the ability of Sbv, miltefosine, and GM-CSF administered intravenously, orally, or topically, respectively, to modify the immune response. Patients were treated with miltefosine plus GM-CSF, miltefosine plus placebo, or Sbv. Mononuclear cells were stimulated with soluble Leishmania antigen (SLA) on day 0 and day 15 of therapy, and cytokine levels were determined in supernatants by ELISA. The lymphocyte proliferation and oxidative burst were evaluated by flow cytometry, and the degree of infection and Leishmania killing by optical microscopy. Proliferation of CD4+ T cells were enhanced in patients using miltefosine and in CD8+ T cells when GM-CSF was associated. Enhancement in the oxidative burst occurred in the miltefosine plus GM-CSF group on day 15 of therapy. Moreover, the number of L. braziliensis in infected monocytes on day 15 as well as the percentage of infected cells was lower after 48- and 72-hour culture in cells from patients treated with miltefosine plus GM-CSF. In addition to the ability of miltefosine to kill Leishmania, the changes in the immune response caused by miltefosine and GM-CSF may increase the cure rate of CL patients using these drugs.

Tansanal total mesorectal excision (TaTME): systematization and mediated results in 10 patients / Excisão total do mesorreto por via transanal (TaTME): sistematização e resultados mediatos em dez pacientes

Abstract Background: Transanal total mesorectal excision is a surgical technique for minimally invasive resection of the rectum and perirectal tissues. It is indicated for patients with medial and distal rectum cancer confined to the mesorectal envelope. This study describes a series of patients undergoing transanal total mesorectal excision. Methods: Ten patients were selected to undergo transanal total mesorectal excision using the SILS-Port® platform. All patients included here had middle or low rectal cancer. Abdominal access for proximal colon mobilization was performed by laparoscopy in all cases. As a rule, in 9 of the 10 cases, the surgical specimen was removed transanally. Result:s During a 41-month period, 10 patients underwent transanal total mesorectal excision based on curative intent. The first indication for transanal total mesorectum excision was medial and distal rectal cancer, locally invasive and confined to the mesortal envelope. The median age of patients with rectal cancer at the time of surgery was 61 years (mean 59.4 years, range 22-78 years), with 80% (8) female and 20% (2) male. The median surgical time was 305' (mean 314', range 260-420'). The median postoperative length of stay was five days (average of 7.3 days, interval of 3-23 days). There was no postoperative mortality. Surgical complications included postoperative ileus (n = 1), bladder paresis (n = 1), and ileostomy stenosis (n = 1). All patients had negative surgical margins for neoplasia and more than 12 resected lymph nodes. The tumors were between 1 and 9 cm from the anal margin. Conclusion: Total transanal mesorectal excision has been shown to be a viable method for oncologic resection of locally advanced rectal cancer with curative intent.

Resumo Contexto: A excisão total do mesorreto por via transanal é uma aborgadem crânio-caudal para a realização de ressecção minimamente invasiva do reto e tecidos perirretais em monobloco. É adequada para pacientes com câncer de reto médio e distal confinados ao envelope mesorretal. Aqui relatamos uma série de pacientes submetidos à excisão total do mesorreto por via transanal. Métodos: Dez pacientes foram selecionados para serem submetidos à excisão total do mesorreto por via transanal utilizando a plataforma SILS-Port®. Todos os pacientes eram portadores de câncer retal de localização extraperitoneal. O acesso abdominal para mobilização do cólon proximal, em todos os casos, foi realizado por laparoscopia. Como regra, a retirada do espécime cirúrgico, em nove casos, ocorreu por via transanal. Resultados: Durante um período de 41 meses, 10 pacientes foram submetidos à excisão total do mesorreto por via transanal com intenção curativa. A indicação primária para excisão total do mesorreto transanal foi o câncer de reto médio e distal, localmente invasor, mas confinado ao envelope mesorretal. A mediana de idade dos pacientes com câncer de reto no momento da cirurgia foi de 61 anos (média de 59,4 anos, faixa de 22-78 anos), sendo 80% (8) do sexo feminino e 20% (2) do sexo masculino. A mediana do tempo cirúrgico foi de 305' (média de 314', intervalo de 260-420'). A mediana do tempo de permanência pós-operatória foi de cinco dias (média de 7,3 dias, intervalo de 3-23 dias). Não houve mortalidade pós-operatória. As complicações cirúrgicas incluíram íleo paralítico (n = 1), paresia vesical (n = 1) e estenose de ileostomia (n = 1). Todos os pacientes tiveram margens cirúrgicas negativas para neoplasia e mais de 12 linfonodos ressecados. Os tumores distavam de 1 a 9 cm da margem anal. Conclusão: A excisão total do mesorreto transanal demonstrou-se um método viável para a ressecção oncológica de câncer de reto localmente avançado com intenção curativa.

Long-term Results of Trimethoprim-Sulfamethoxazole Versus Placebo to Reduce the Risk of Recurrent Toxoplasma gondii Retinochoroiditis.

PURPOSE: To compare the effects of 1 year of treatment with trimethoprim-sulfamethoxazole (TMP-SMZ) vs placebo in reducing the risk of recurrence of toxoplasmic retinochoroiditis during a 6-year follow-up period. DESIGN: Randomized, double-masked clinical trial. METHODS: This cohort included 141 subjects recruited in Campinas, Brazil. The inclusion criterion was unilateral active recurrent toxoplasmic retinochoroiditis. All subjects were treated with 1 dose of TMP-SMZ (160 mg/800 mg) twice daily for 45 days, and all lesions healed after this treatment. After this initial treatment, subjects were randomly assigned to group 1 (1 TMP-SMZ dose every other day for 311 days) or group 2 (1 identical placebo tablet containing starch with no active ingredients every other day for 311 days). Between the second and sixth years of follow-up appointments, none of the subjects received treatment unless a new recurrence episode had occurred. The primary outcomes were recurrent toxoplasmic retinochoroiditis within the first year of follow-up and recurrent toxoplasmic retinochoroiditis in the 6 years of follow-up. RESULTS: The cumulative probability of recurrence 1, 2, 3, 4, 5, and 6 years after the initial infection was, respectively, 13.0% (9/69), 17.4% (12/69), 20.3% (14/69), 23.2% (16/69), 26.1% (18/69), and 27.5% (19/69) in the placebo group and 0%, 0%, 0%, 0%, 0%, and 1.4% (1/72) in the TMP-SMZ group (P < .001; log-rank test). There were 3 cases (3/69; 4.3%) of multiple recurrences in the same individual in the placebo group. No treatment-limiting toxicity or side effects were observed in either group. New recurrences were more frequent among female subjects. CONCLUSIONS: TMP-SMZ may be used safely for prophylaxis of recurrent toxoplasmic retinochoroiditis and may provide long-term benefits.