The Influence of Antithymocyte Globulin Dose on the Incidence of CMV Infection in High-risk Kidney Transplant Recipients Without Pharmacological Prophylaxis.

BACKGROUND: Optimizing antithymocyte globulin (ATG) dosage is critical, particularly for high-risk kidney transplant (KT) recipients without cytomegalovirus (CMV) prophylaxis. METHODS: We studied 630 KT recipients with expanded criteria donors or panel reactive antibody ≥50% at Hospital do Rim, Brazil (January 1, 2013 to May 21, 2015) to determine whether a single ATG dose was safe and effective in patients without CMV prophylaxis. Patients received ≥4 doses (1-1.5 mg/kg/per dose) until June 17, 2014, when the induction protocol changed to a single ATG dose (3 mg/kg). We used Cox regression to compare the risk of CMV infection and acute rejection (AR) among KT recipients by ATG dose. RESULTS: Adjusting for clinical and transplant factors, a single ATG dose was associated with a lower risk of CMV infection (adjusted hazard ratio [aHR]: 0.63; 95% confidence interval [CI], 0.42-0.93; P = 0.02) and a similar risk of AR (aHR: 1.16; 95% CI, 0.47-2.83; P = 0.8), compared to multiple doses. We found no differences in death-censored graft loss (5.0% versus 4.8%, aHR: 1.06; 95% CI, 0.51-2.23; P = 0.9) or mortality (4.7% versus 3.4%; aHR: 1.42; 95% CI, 0.62-3.24; P = 0.4) at 1-year post-KT by ATG dose. CONCLUSIONS: In our study of high-risk KT recipients without CMV prophylaxis, a single ATG dose decreased the risk of CMV infection without increasing the risk of AR or compromising graft or patient survival.

Bronchopulmonary Dysplasia in Very Preterm Infants with Symptomatic Congenital Cytomegalovirus Infection: A Propensity Score-Matched Analysis.

OBJECTIVE: To assess whether symptomatic congenital cytomegalovirus infection (cCMV) is associated with bronchopulmonary dysplasia (BPD) and mortality in very preterm infants (gestational age ≤32 weeks). STUDY DESIGN: We performed a retrospective study using the Kids' Inpatient Database for 2003, 2006, 2009, and 2012. Diagnoses of BPD and symptomatic cCMV were determined using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Among patients with in-hospital birth at ≤32 weeks of gestation, cases of symptomatic cCMV were matched with infants without cCMV using propensity score matching at 1:2 ratio. Outcomes of BPD and in-hospital mortality were assessed using conditional logistic regression. RESULTS: Of 204 818 in-hospital births with gestational age ≤32 weeks, we identified 208 cases of symptomatic cCMV, 177 of which underwent matching. Symptomatic cCMV was associated with higher odds of BPD (OR, 2.34; 95% CI, 1.41-3.87), but was not significantly associated with in-hospital all-cause mortality (OR, 1.18, 95% CI, 0.64-2.17). CONCLUSIONS: Symptomatic cCMV was associated with BPD but not with in-hospital mortality among very preterm infants. Further study is needed to determine the risk of BPD among infants with cCMV to allow for evaluation of possible preventive measures.

Late cytomegalovirus (CMV) infections after kidney transplantation under the preemptive strategy: Risk factors and clinical aspects.

BACKGROUND: Late cytomegalovirus infections (LCMV) after the cessation of prophylaxis are well described. We aimed to assess clinical and epidemiological data on late-occurring cytomegalovirus (CMV) infections in the absence of CMV prophylaxis in a cohort of kidney transplant patients. METHODS: In a cohort of kidney transplant recipients not employing CMV-specific prophylaxis, patients with CMV infections occurring after 6 months of transplantation were compared to patients with CMV infections diagnosed within the first 6 months (early infections). The main objectives were to compare clinical outcomes and evaluate risk factors for late CMV infection. RESULTS: A total of 556 patients were evaluated. Forty-three patients with LCMV infections were compared to 513 patients with early CMV infections. LCMV infections occurred after a median of 473 days of transplantation and had a more severe course, with a statistically significant higher rate of invasive disease and graft loss (60.5% vs 21.6% and 11.6% vs 3.1% respectively). Thirty-day mortality was twice as high for patients with LCMV, but did not reach statistical significance (9.3% vs 4.3%). By multivariate analysis, employment of antilymphocyte therapy early after transplantation and tacrolimus as initial immunosuppressive therapy were significantly protective for the occurrence of LCMV infections. CONCLUSION: Late CMV infections in the absence of specific prophylaxis after kidney transplantation have a more severe outcome when compared to early infections and occur in patients less immunosuppressed early after transplantation.

Enfermedad por citomegalovirus en el trasplante renal / Disease by cytomegalovirus in renal transplants

Introducción: La enfermedad por citomegalovirus en el trasplante renal representa una amenaza para la supervivencia del injerto y del paciente. Objetivo: Caracterizar la morbimortalidad de la enfermedad por citomegalovirus en receptores de trasplante renal. Métodos: Se realizó un estudio prospectivo, descriptivo y observacional en el Hospital Provincial Clínico Quirúrgico Universitario Arnaldo Milián Castro entre 2014 y 2016 que incluyó 49 pacientes. Se eligieron variables sociodemográficas, etiología de la nefropatía originaria, la forma de presentación de la enfermedad, la comorbilidad, las pautas inmunosupresoras empleadas, la respuesta al ganciclovir y el estado del paciente al egreso, así como las causas de muerte. Resultados: La edad promedio fue 46,55 (±13,02 años) con predominio del sexo masculino (relación 2:1) (p=0,727). La forma inespecífica y el momento de aparición tardía fue mayoritaria, 81,63 por ciento (p=0,498). La comorbilidad preponderante fue la infección del tracto urinario. La pauta inmunosupresora de prednisona-micofenolato mofetilo se empleó en 26 pacientes (53,06 por ciento); 33 pacientes (67,35 por ciento) respondieron adecuadamente al ganciclovir (p=0,907) y la tercera parte (26,53 por ciento) de los pacientes fallecieron por insuficiencia respiratoria aguda (p=0,447). Conclusiones: La enfermedad por citomegalovirus constituye una amenaza real en pacientes inmunocomprometidos(AU)

Introduction: The disease by cytomegalovirus in the renal transplant represents a threat for the survival of the graft and of the patient. Objective: To characterize the morbidity and mortality of the disease by cytomegalovirus in recipients of renal transplant. Methods: A prospective, descriptive and observational study was carried out in Arnaldo Milián Castro Provincial Clinical- Surgical University Hospital between 2014 and 2016 that included 49 patients. Socio-demographic variables, ethiology of the original nephropathy, form of presentation of the disease, comorbidity, immunosuppressive guidelines used, the response to ganciclovir and the condition of the patient in the moment of discharge were chosen, as well as the causes of death. Results: The average age was 46,55 (±13,02 years) with predominance of the masculine sex (relation 2:1) (p=0,727). The unspecific form and the moment of late appearance was a majority (81, 63 percent) (p=0,498). The preponderant comorbility was the infection of the urinary tract. The immunosuppressive guideline of prednisone-mycophenolate mofetil was used in 26 patients (53, 06 percent); 33 patients (67,35 percent) responded adequately to ganciclovir (p=0,907) and the third part (26,53 percent) of the patients died due to acute respiratory failure (p=0,447). Conclusions: The disease by cytomegalovirus constitutes a real threat in inmunocompromised patients(AU)

Synergistic effect of KIR ligands missing and cytomegalovirus reactivation in improving outcomes of haematopoietic stem cell transplantation from HLA-matched sibling donor for treatment of myeloid malignancies.

The goal of this study was to evaluate the influence of KIR-HLA genotypes on the outcome of patients undergoing treatment for haematological malignancies by non-T-depleted lymphocyte haematopoietic stem cell transplantation (HSCT) from HLA-matched sibling donors. The prospective study was conducted at the Center of Hematology, University of Campinas, and 50 patients and their donors were followed up from 2008 to 2014. KIR and HLA class I genes were genotyped and patients grouped based on the presence of KIR ligands combined with KIR genotype of their respective donors. Patients with all KIR ligands present (n=13) had a significantly higher (p=0.04) incidence of acute graft-versus-host-disease (GVHD) than patients with one or more KIR ligands missing (n=37). The overall survival following transplantation of patients with myeloid malignancies (n=27) was significantly higher (p=0.035) in the group with one or more KIR ligands missing (n=18) than in the group with all ligands present (n=9). Presence of KIR2DS2 was associated with a worsening of HSCT outcome while reactivation of cytomegalovirus (CMV) infection improved the outcome of patients with one or more KIR ligands missing. Our results indicate that KIR-HLA interactions affect the outcome of the HLA-matched transplantation, particularly in patients with myeloid malignancies.

The role of secondary cytomegalovirus prophylaxis for kidney and liver transplant recipients.

BACKGROUND: The role of secondary cytomegalovirus (CMV) prophylaxis, defined as the continuation of valganciclovir to prevent relapse after the successful treatment of CMV disease, is not well understood. METHODS: Cases of CMV disease in patients who underwent kidney or liver transplantation from January 2001 to January 2010 were reviewed to determine if the use of secondary prophylaxis was associated with fewer relapses or other favorable outcomes. Secondary prophylaxis was used at the discretion of each treating clinician, without an institutional protocol. RESULTS: Twenty-two cases of CMV disease in kidney transplant recipients and 20 cases in liver transplant recipients were included. Relapsed CMV disease was significantly more common among kidney transplant recipients (5/22 vs. 0/20, P = 0.049). Of 22 kidney transplant recipients, 16 received secondary prophylaxis. After a mean of 3.7 years, relapsed CMV disease occurred in three of 16 patients who received secondary prophylaxis and in two of six who did not. Among liver transplant recipients, only two of 20 patients received secondary prophylaxis. After a mean of 3.2 years, no relapsed CMV disease occurred. The use of secondary prophylaxis was not significantly associated with fewer episodes of CMV relapse, graft loss, or death. Time to clearance of CMV viremia during treatment was significantly longer in those who relapsed (mean, 30 days vs. 20 days; P = 0.037). CONCLUSION: These findings suggest that secondary CMV prophylaxis may not provide additional benefit after the successful treatment of CMV disease, particularly among liver transplant recipients.

Clinical, biochemical, and neuroimaging findings predict long-term neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection.

OBJECTIVE: To evaluate clinical, biochemical, and neuroimaging findings as predictors of neurodevelopmental outcome in patients with symptomatic congenital cytomegalovirus (CMV). STUDY DESIGN: The study cohort comprised 26 patients with symptomatic congenital CMV born between 1993 and 2009 in a single center. Absolute and weight deficit-adjusted head circumference were considered. Cerebrospinal fluid (CSF) investigations included standard cytochemical analysis, determination of beta2-microglobulin (ß2-m), neuron-specific enolase, and CMV DNA detection. Neuroimaging was classified according to a validated scoring system comprising calcifications, ventriculomegaly, and atrophy, with findings graded from 0 to 3. Systematic long-term neurodevelopmental assessment included motor function, cognition, behavior, hearing, vision, and epilepsy. Sequelae were graded as mild/absent, moderate, or severe; adverse outcome was defined as death or moderate to severe disability. RESULTS: Three children died. The mean age at follow-up of the survivors was 8.7 ± 5.3 years (range, 19 months to 18.0 years). Neonatal findings showing a significant association with adverse outcome were relative microcephaly, CSF ß2-m concentrations, and grade 2-3 neuroimaging abnormalities (P < .05). Receiver operator characteristic curve analysis indicated that the most accurate single factor for predicting unfavorable outcome was CSF ß2-m >7.9 mg/L (area under the curve, 0.84 ± 0.08; sensitivity, 69%; specificity, 100%). The combination of CSF ß2-m >7.9 mg/L and moderate-severe neuroimaging alterations improved predictive ability (area under the curve, 0.92 ± 0.06; sensitivity, 87%; specificity, 100%). CONCLUSION: Adjusted head circumference, CSF ß2-m level, and neuroimaging studies have prognostic significance for neurodevelopmental outcome in newborns with congenital CMV. A combination of early findings improves the predictive value.

Haploidentical stem cell transplantation for children with high-risk leukemia.

BACKGROUND: The Chilean population is ethnically diverse, and more than 50% of children referred for hematopoietic stem cell transplantation (HSCT) lack a suitable donor. PROCEDURE: To expand the donor pool, we assessed the feasibility, tolerance, and efficacy of using a haploidentical (HI) donor and a reduced-intensity conditioning regimen for high-risk pediatric leukemia. This study was facilitated by technology transfer from St. Jude Children's Research Hospital over the 2 preceding years. RESULTS: Between March 2006 and April 2009, 10 patients (median age, 9.8 years) received T cell-depleted grafts at Calvo Mackenna Hospital in Santiago. Median cell doses were CD34+: 7.45 × 10(6)/kg (range, 4.00-20.20 × 10(6)/kg); CD3+: 0.88 × 10(5)/kg (0.11-1.35 × 10(5)/kg); and CD56+: 71.30 × 10(6)/kg (31.50-131.80 × 10(6)/kg). Nine patients experienced complete engraftment; six of the nine remain alive and clinically well 13-50 months post-HSCT. Three patients died after bone marrow relapse, while only one died of transplant-related causes. Virus reactivation was the main post-transplant complication: 5/10 had positive CMV PCR but none had CMV disease. One patient developed acute GvHD > grade II and only one had chronic GvHD. CONCLUSIONS: HI-HSCT is feasible in our setting, offers a rational treatment option, and expands the donor pool significantly for children with high-risk leukemia in a developing country. This information is especially relevant to other ethnically diverse populations that are poorly represented in international donor registries.

Gastrointestinal cytomegalovirus disease in renal transplant recipients: a case series.

The purpose of this article was to report a series of 23 renal transplant recipients with histologically proven and immunohistochemically confirmed cytomegalovirus (CMV) lesions in the gastrointestinal tract (GIT) and to assess the risk factors associated with severe disease/mortality. CMV patients (n=23) were allocated into two groups: those who died (n=6) and those considered cured (n=17). Overall mortality rate was 26% (6/23). Initial symptoms suggestive of lower GIT involvement were observed in all death cases and in 35.3% of those cured (p=0.01). Enterorrhagia was seen in 83.3% of the patients who died. Death risk increased twofold (RR 2 [1.13-3.52], p=0.01) when symptoms of lower GIT involvement were initially observed and sixfold when enterrohagia was present (RR 6 [1.1-35.9], p=0.001). Among death cases, mean time at diagnosis was significantly more distant (2002±2.9×2008±1.6, p=0.04). The difference in mortality rates seen as service practices changed along the years demonstrates the importance of early diagnosis.

Impact of cytomegalovirus infection in lung transplant patients under universal prophylaxis: single-center experience in Brazil.

INTRODUCTION: Cytomegalovirus (CMV) infection, a common complication in lung transplant (LT) patients, is associated with worse outcomes. Therefore, prophylaxis and surveillance with preemptive treatment is recommended. OBJECTIVES: Describe the epidemiology and impact on mortality of CMV infection in LT patients receiving CMV prophylaxis. METHODS: Single-center retrospective cohort of LT recipients from August 2003 to March 2008. We excluded patients with survival or follow-up shorter than 30 days. We reviewed medical charts and all CMV pp65 antigen results. RESULTS: Forty-seven patients met the inclusion criteria and 19 (40%) developed a CMV event: eight CMV infections, seven CMV syndromes, and 15 CMV diseases. The mean number of CMV events for each patient was 1.68 +/- 0.88. Twelve patients developed CMV events during prophylaxis (5/12 had CMV serology D+/R-). Forty-six of the 47 patients had at least one episode of acute rejection (mean 2.23 +/- 1.1). Median follow-up was 22 months (range = 3-50). There were seven deaths. Upon univariate analysis, CMV events were related to greater mortality (P = .04), especially if the patient experienced more than two events (P = .013) and if the first event occurred during the first 3 months after LT (P = .003). Nevertheless, a marginally significant relationship between CMV event during the first 3 months after LT and mortality was observed in the multivariate analysis (hazards ratio: 7.46; 95% confidence interval: 0.98-56.63; P = .052). Patients with CMV events more than 3 months post-LT showed the same survival as those who remained CMV-free. CONCLUSION: Prophylaxis and preemptive treatment are safe and effective; however, the patients who develop CMV events during prophylaxis experience a worse prognosis.

Strategies for prevention of cytomegalovirus infection in renal transplant patients.

OBJECTIVE: Cytomegalovirus (CMV) constitutes the principal viral infection in renal transplant patients. The indirect consequences of CMV infection increase the risks for acute and chronic rejection, secondary infections, lymphoproliferative disorders, atherosclerosis, and cardiovascular deaths. The direct effects depend on the affected organ. There have been strategies to prevent CMV disease: prophylaxis and preemptive strategy. The aim of this study was to compare the incidences of disease and infection due to CMV among our patients. PATIENTS AND METHODS: We performed a retrospective analysis of all our renal transplant patients between January 2000 and January 2008. RESULTS: Four groups were identified among 94 patients: without any preventive strategy; brief prophylaxis; formal prophylaxis; and preemptive treatment. There were no significant differences among the groups in the incidences of CMV disease, acute renal rejection, or survival. The greatest number of infections was registered in the group with brief prophylaxis (P = .006); 50% of the registered infections occurred before 150 days posttransplantation. CONCLUSIONS: We concluded that the preemptive strategy is appropriate for the low-risk patient, while prevention with antiviral drugs should be reserved for intermediate- and high-risk patients. A brief treatment for prevention is an alternative to prevent CMV disease, but it needs to be followed with serial, long-term evaluation of antigenemia for >150 days posttransplantation.

Comparação dos métodos de reação em cadeia da polimerase qualitativo e antigenemia PP65 para o diagnóstico de infecção por citomegalovírus em pacientes imunossuprimidos / Comparison between qualitative polymerase chain reaction and PP65 antigenemia for the diagnosis of cytomegalovirus infection in immunosuppressed patients

Introdução: A infecção por citomegalovírus (CMV) é freqüente e acomete com significativa morbimortalidade indivíduos imunossuprimidos, especialmente transplantados e pacientes HIV positivos com doença avançada. Objetivo: Este estudo visou a comparar o desempenho dos métodos reação em cadeia da polimerase qualitativo (PCR) e antigenemia pp65 para o diagnóstico de infecção por CMV em pacientes imunossuprimidos. Métodos: O estudo foi realizado em 216 amostras de sangue total coletadas de 85 pacientes, entre agosto de 2006 e janeiro de 2007, provenientes da internação ou ambulatório do Hospital de Clínicas de Porto Alegre (HCPA). Resultados: Entre as 216 amostras analisadas, 35 amostras apresentaram resultados positivos e 181 amostras apresentaram resultados negativos em uma e/ou outra técnica. Destas 35 amostras positivas, 16 foram positivas em ambas as técnicas; 12 apresentaram-se positivas pela PCR e negativas pela antigenemia; e sete amostras apresentaram-se positivas pela antigenemia e negativas pela PCR. Considerando a antigenemia como padrão-ouro, a técnica de PCR mostrou sensibilidade de 69,6%, especificidade de 93,8%, valor preditivo positivo de 57,1% e valor preditivo negativo de 96,3%. O coeficiente de correlação kappa foi de 0,578. Discussão: Este resultado demonstra que a PCR qualitativa apresenta moderada sensibilidade e alta especificidade para o diagnóstico de infecção para CMV. Apesar de suas limitações, pode ser utilizada para exclusão do diagnóstico em pacientes com suspeita de infecção por CMV, por ser um método mais simples, de baixo custo e de fácil execução.

Introduction: Cytomegalovirus (CMV) infection is frequent and has significant morbidity and mortality in immunosuppressed individuals, especially in transplanted and HIV-positive patients with advanced disease. Objective: This study compared the performance of qualitative polymerase chain reaction (PCR) and pp65 antigenemia methods for the diagnosis of CMV infection in immunosuppressed patients. Methods: A total of 216 of peripheral blood samples were collected from 85 inpatients or outpatients, from August 2006 through January 2007 from Hospital de Clínicas de Porto Alegre (HCPA). Results: Of the 216 samples, 35 had positive results and 181 were negative with regard to one and/or another technique. Of the 35 positive samples, 16 were positive in both techniques; 12 were positive for PCR and negative for antigenemia, and seven samples were positive for antigenemia but negative for PCR. Considering antigenemia as the gold standard, the PCR technique showed sensitivity of 69.6%, specificity of 93.8%, positive predictive value of 57.1%, and negative predictive value of 96.3%. The kappa correlation coefficient was 0.578. Discussion: These results demonstrate that the qualitative PCR has moderate sensitivity and high specificity for the diagnosis of CMV infection. Despite its limitations, it can be used for diagnosis exclusion in patients under CMV infection suspicion because of its simplicity, low cost and of easy execution.

Autopsy-proven causes of death in lungs of patients immunocompromised by secondary interstitial pneumonia.

PURPOSE: To present the more frequent associations found in autopsies of immunocompromised patients who developed secondary interstitial pneumonia as well as the risk of death (odds ratio) in having specific secondary interstitial pneumonia according to the cause of immunocompromise. METHOD: From January 1994 to March 2004, 17,000 autopsies were performed at Hospital das Clínicas, São Paulo University Medical School. After examining the pathology report review, we selected 558 of these autopsies (3.28%) from patients aged 15 years or more with primary underlying diseases who developed radiologically diffuse infiltrates of the lung during their hospital course and died after secondary interstitial pneumonia (bronchopneumonia, lobar pneumonia, interstitial pneumonia, diffuse alveolar damage, pulmonary recurrence of underlying disease, drug-induced lung disease, cardiogenic pulmonary edema, or pulmonary embolism). Histology slides were reviewed by experienced pathologists to confirm or not the presence of secondary interstitial pneumonia. Statistical analysis included the Fisher exact test to verify any association between histopathology and the cause of immunocompromise; a logistic regression was used to predict the risk of death for specific histological findings for each of the independent variables in the model. RESULTS: Secondary interstitial pneumonia was histologically represented by diffuse interstitial pneumonitis ranging from mild nonspecific findings (n = 213) to a pattern of diffuse alveolar damage (n = 273). The principal causes of immunocompromise in patients with diffuse alveolar damage were sepsis (136 cases), neoplasia (113 cases), diabetes mellitus (37 cases), and transplantation (48 cases). A high risk of death by pulmonary edema was found for patients with carcinoma of colon. Similarly, in patients with lung cancer or cachexia, A high risk of death by bronchopneumonia (OR = 3.6; OR = 2.6, respectively) was found. Pulmonary thromboembolism was associated with an appreciable risk of death (OR = 2.4) in patients with arterial hypertension. The risk of death was also high in patients presenting hepatic cancer (OR = 2.5) or steroid therapy (OR = 2.4) who developed pulmonary hemorrhage as the histological pattern of secondary interstitial pneumonia . The risk of death by lung metastasis was also elevated (OR = 1.6) for patients that were immunosuppressed after radiotherapy. CONCLUSION: Patients with secondary immunosuppression who developed secondary interstitial pneumonia during treatment in hospital should be evaluated to avoid death by diffuse alveolar damage, pulmonary edema, bronchopneumonia, lung hemorrhage, pulmonary thromboembolism, or lung metastasis. The high-risk patients are those immunosuppressed by hematologic disease; those under steroid treatment; or those with colon or hepatic carcinoma, cachexia, or arterial hypertension.

Autopsy-proven causes of death in lungs of patients immunocompromised by secondary interstitial pneumonia

PURPOSE: To present the more frequent associations found in autopsies of immunocompromised patients who developed secondary interstitial pneumonia as well as the risk of death (odds ratio) in having specific secondary interstitial pneumonia according to the cause of immunocompromise. METHOD: From January 1994 to March 2004, 17,000 autopsies were performed at Hospital das Clínicas, São Paulo University Medical School. After examining the pathology report review, we selected 558 of these autopsies (3.28 percent) from patients aged 15 years or more with primary underlying diseases who developed radiologically diffuse infiltrates of the lung during their hospital course and died after secondary interstitial pneumonia (bronchopneumonia, lobar pneumonia, interstitial pneumonia, diffuse alveolar damage, pulmonary recurrence of underlying disease, drug-induced lung disease, cardiogenic pulmonary edema, or pulmonary embolism). Histology slides were reviewed by experienced pathologists to confirm or not the presence of secondary interstitial pneumonia. Statistical analysis included the Fisher exact test to verify any association between histopathology and the cause of immunocompromise; a logistic regression was used to predict the risk of death for specific histological findings for each of the independent variables in the model. RESULTS: Secondary interstitial pneumonia was histologically represented by diffuse interstitial pneumonitis ranging from mild nonspecific findings (n = 213) to a pattern of diffuse alveolar damage (n = 273). The principal causes of immunocompromise in patients with diffuse alveolar damage were sepsis (136 cases), neoplasia (113 cases), diabetes mellitus (37 cases), and transplantation (48 cases). A high risk of death by pulmonary edema was found for patients with carcinoma of colon. Similarly, in patients with lung cancer or cachexia, A high risk of death by bronchopneumonia (OR = 3.6; OR = 2.6, respectively) was found. Pulmonary...

OBJETIVO: Apresentar as associações mais freqüentes encontradas em autópsias de pacientes imunossuprimidos que desenvolveram pneumonia intersticial secundária bem como o risco de óbito (Odds Ratio) de desenvolver PIS associada à causa da imunossupressão. MÉTODO: De janeiro de 1994 a março de 2004, 17000 autópsias foram realizadas no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. A partir da revisão dos laudos patológicos foram selecionados 558 destas autópsias (3,28 por cento) de pacientes com 15 anos de idade ou mais, com alguma doença de base que desenvolveu um infiltrado pulmonar radiologicamente difuso durante o curso da hospitalização e que depois foi para óbito com pneumonia intersticial secundária (broncopneumonia, pneumonia lobar, pneumonia intersticial, dano alveolar difuso, doença pulmonar recorrente, doença pulmonar induzida por drogas, edema pulmonar cardiogênico e embolismo pulmonar). As lâminas histológicas foram revisadas por patologistas experientes para confirmar ou não a presença de pneumonia intersticial secundária. A análise estatística incluiu o "Teste exato de Fisher" para verificar associação entre a histolopatologia e causa de imunocomprometimento; e regressão logística para predizer o risco de óbito por achados histológicos específicos para cada variável independente do modelo. RESULTADOS: A pneumonia intersticial secundária foi representada histológicamente por pneumonite intersticial difusa variando de características não especificas leves (n=213) ao padrão histológico de dano alveolar difuso (n=273). A principal causa de imunossupressão nos pacientes com dano alveolar difuso foi sepse (136 casos), neoplasia (113 casos), diabetes melito (37 casos) e transplantados (37 casos). O maior risco de morte por edema pulmonar foi encontrado nos pacientes com carcinoma de cólon. Da mesma forma, nos pacientes com câncer pulmonar ou cachexia ocorreu um alto risco de morte (OR=3.6; OR=2.6, respectivamente)...

No cytomegalovirus-related deaths after non-ablative stem cell allografts.

Cytomegalovirus (CMV)-related deaths and data of clinically evident CMV disease were assessed in a group of 47 individuals given allogeneic non-myeloablative hematopoietic stem cell transplants (NST). IgG anti-CMV antibodies were found in 56% of the donors and 76% of the receptors. Prophylactic ganciclovir was given to only 12 of the recipients during 100 days after the graft. There were no CMV-related deaths and clinically overt CMV disease was not found in any individual. The follow up post-transplant period of the patients, ranges between 30 and 810 days (median 242 days), the actuarial median survival (SV) is above 810 days and has not been reached, whereas the 810-days SV is 60%. Eighteen patients (38%) died 30-480 days after the transplant; four failed to engraft and died because of progressive disease; three died as a consequence of graft versus host disease (GVHD), whereas eleven individuals had a relapse of the malignancy and died. It is possible that the reduced bone marrow damage during NST, the prompt recovery of both the hematopoiesis and immune function in this type of allografts and the use of peripheral blood hematopoietic stem cell (HSC) is responsible for the absence of CMV-related deaths and clinical disease despite a high prevalence of CMV infection in these individuals.

Extended antigenemia surveillance and late cytomegalovirus infection after allogeneic BMT.

Late CMV disease remains a major concern in allogeneic BMT recipients. Few surveillance data are available on the occurrence of CMV infection and recurrences after day +100. We evaluated the occurrence of antigenemia (AG) recurrences until day +365 in 76 patients who received pre-emptive ganciclovir (GCV) therapy prompted by AG > or = 2 positive cells. Sixty-two episodes of AG recurrences were detected in 33 of the 52 patients who had positive AG. Survival analysis showed a 45.4% probability of AG recurrence on day +100, 64.8% on day +180 and 71.2% on day +365. The median time for AG recurrences was 113 (35 to 343) days. Thirty-five of the 62 episodes (56.4%) occurred after day +100. More than 70% of the patients responded to a 2-week course of GCV and no CMV disease was observed shortly after discontinuation of GCV. The Cox proportional model showed a significant effect of AG recurrences on patient's follow-up only when the patient developed chronic GVHD (P = 0.012). Extended surveillance favored early introduction of GCV and late CMV pneumonia occurred in only one of the 76 patients (1.3%). AG recurrences are frequent after day +100 and extended surveillance until day +365 is recommended for patients who develop chronic GvHD.

[Clinical profile of cytomegalovirus (CMV) enterocolitis in acquired immunodeficiency syndrome]. / Perfil clínico da Enterocolite por Citomegalovírus (CMV) na síndrome da imunodeficiência adquirida (Aids).

OBJECTIVE: To determine the clinical profile of CMV colitis in AIDS patients, comparing clinical, endoscopic parameters and survival time between 2 groups of AIDS patients having chronic diarrhea. Group A being CMV colitis and group B without CMV colitis. METHODS: 48 patients with diarrhea that lasted more than 30 days, being 27 in Group A and 21 in Group B, were studied. Age, risk factors, interval time between the diagnosis of HIV infection and the beginning of diarrhea, hematochesia, the endoscopic findings and life table in both groups, were analysed. All of them were diagnosed by stool culture and stools for ovum and parasites, along colonoscopy with biopsies. The unpaired t test was used to assess statistical significance of differences observed in the means of continuous and the chi-square with Yates correction for non-parametric variables. The survival curves were assessed by the Kaplan-Meier and the Mantel-Haenszel's tests. A P value of less than 0,05 was considered to indicate statistical significance. RESULTS: The mucosal lesions associated with the CMV infection are typically ulcerative on a background of hemorrhagic erythema 14 (51,8%) p < 0,01. The life table analysis disclosed shorter survival time in the CMV colitis group 0,005> P>0,001. The others studied data did not achieve statistical significance. CONCLUSIONS: AIDS patients with CMV colitis have a poorer long-term survival. Among the colonoscopic findings, ulcerations with hemorrhagic background were the most common lesions.

Analysis of time-dependent risks for infection, rejection, and death after pulmonary transplantation.

Infection and rejection remain the greatest threats to the survival of pulmonary allograft recipients. Furthermore, a relationship may exist between these events, because the occurrence of one may predispose to the other. By using multivariate analysis for repeated events, we analyzed the risk factors for bacterial, fungal, and viral infection, grade II or greater acute rejection, and death among 239 lung transplant recipients who received 250 allografts between January 1988 and September 1993. A total of 90 deaths, 491 episodes of acute rejection, and 542 infectious episodes occurred during a follow-up of 6 to 71 months. The hazard or risk patterns of death, infection, and rejection each followed an extremely high risk during the first 100 days after transplantation, a second modest risk period at 800 to 1200 days, and a lower constant risk. Infection and graft failure manifested by diffuse alveolar damage were the major causes of early death (< 100 days), whereas infection and chronic rejection were primary causes of later death after pulmonary transplantation. By multivariate analysis, cytomegalovirus mismatching risk for primary infection was the most significant risk factor for death, rejection, and infection. Absence of cytomegalovirus prophylaxis was also a risk factor for early and late death and late infection. Survival of recipients who received cytomegalovirus prophylaxis was significantly improved. Immunosuppression based on cyclosporine versus FK 506 was a risk factor for late death and late infection. Graft failure manifested by diffuse alveolar damage/adult respiratory distress syndrome was a significant risk for death late after transplantation. These data suggest the following: (1) The hazard for death, infection, and rejection after pulmonary transplantation appears biphasic; (2) lower survival is associated with ischemia-reperfusion lung injury represented by diffuse alveolar damage/adult respiratory distress syndrome; (3) cytomegalovirus mismatch, absence of cytomegalovirus prophylaxis, and development of cytomegalovirus disease are significant threats for death, rejection, and infection after pulmonary transplantation; (4) prevention of cytomegalovirus disease should improve survival by decreasing the prevalence of infection and rejection.

Cytomegalovirus and Pneumocystis carinii pneumonia in children with acquired immunodeficiency syndrome.

To ascertain the effect of cytomegalovirus (CMV) infection on the course of Pneumocystis carinii pneumonia (PCP) in children with acquired immunodeficiency syndrome (AIDS), we reviewed the charts of all children with AIDS who also had a lung biopsy specimen or a bronchoalveolar lavage specimen cultured for CMV at the time PCP was diagnosed. The data indicate that children with AIDS and PCP whose cultures are positive for CMV do not have a poorer prognosis during a first episode of PCP compared with children whose cultures are negative for CMV.