Tolerability of four-drug antiretroviral combination therapy in primary HIV-1 infection.

OBJECTIVES: Rapid initiation of antiretroviral therapy (ART) is important for individuals with high baseline viral loads, such as in primary HIV-1 infection (PHI). Four-drug regimens are sometimes considered; however, data are lacking on tolerability. We aimed to evaluate the tolerability of four-drug regimens used in the Research in Viral Eradication of HIV-1 Reservoirs (RIVER) study. METHODS: At enrolment, ART-naïve adult participants or those newly commenced on ART were initiated or intensified to four-drug regimens within 4 weeks of PHI. Rapid start was defined as pre-confirmation or ≤ 7 days of confirmed diagnosis. Primary and secondary outcomes were patient-reported adherence measured by 7-day recall and regimen switches between enrolment and randomization, respectively. RESULTS: Overall, 54 men were included: 72.2% were of white ethnicity, with a median age of 32 years old, 42.6% had a viral load of ≥ 100 000 HIV-1 RNA copies/mL, and in 92.6% sex with men was the mode of acquisition of HIV-1. Twenty (37%) started a four-drug regimen and 34 (63%) were intensified. Rapid ART initiation occurred in 28%, 100% started in ≤ 4 weeks. By weeks 4, 12, and 24, 37.0%, 69.0%, and 94.0% were undetectable (viral load < 50 copies/mL), respectively. Adherence rates of 100% at weeks 4, 12, 22 and 24 were reported in 88.9%, 87.0%, 82.4% and 94.1% of participants, respectively. Five individuals switched to three drugs, four changed their regimen constituents, and two switched post-randomization. CONCLUSIONS: Overall, four-drug regimens were well tolerated and had high levels of adherence. Whilst their benefit over three-drug regimens is lacking, our findings should provide reassurance if a temporarily intensified regimen is clinically indicated to help facilitate treatment.

Week 96 results of the randomized, multicentre Maraviroc Switch (MARCH) study.

OBJECTIVES: The Maraviroc Switch (MARCH) study week 48 data demonstrated that maraviroc, a chemokine receptor-5 (CCR5) inhibitor, was a safe and effective switch for the ritonavir-boosted protease inhibitor (PI/r) component of a two nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] plus PI/r-based antiretroviral regimen in patients with R5-tropic virus. Here we report the durability of this finding. METHODS: MARCH, an international, multicentre, randomized, 96-week open-label switch study, enrolled HIV-1-infected adults with R5-tropic virus who were stable (> 24 weeks) and virologically suppressed [plasma viral load (pVL) < 50 HIV-1 RNA copies/mL]. Participants were randomized to continue their current PI/r-based regimen (PI/r) or to switch to MVC plus two N(t)RTIs (MVC) (1:2 randomization). The primary endpoint was the difference in the proportion with pVL < 200 copies/mL at 96 weeks. The switch arm was defined as noninferior if the lower limit of the 95% confidence interval (CI) for the difference was < -12% in the intention-to-treat (ITT) population. Safety endpoints (the difference in the mean change from baseline or a comparison of proportions) were analysed as key secondary endpoints. RESULTS: Eighty-two (PI/r) and 156 (MVC) participants were randomized and included in the ITT analysis; 71 (87%) and 130 (83%) were in follow-up and on therapy at week 96. At week 96, 89.0% and 90.4% in the PI/r and MVC arms, respectively, had pVL < 50 copies/mL (95% CI -6.6, 10.2). Moreover, in those switching away from PI/r, there were significant reductions in mean total cholesterol (differences 0.31 mmol/L; P = 0.02) and triglycerides (difference 0.44 mmol/L; P < 0.001). Changes in CD4 T-cell count, renal function, and serious and nonserious adverse events were similar in the two arms. CONCLUSIONS: MVC as a switch for a PI/r is safe and effective at maintaining virological suppression while having significant lipid benefits over 96 weeks.

Tuberculosis screening in patients with HIV: An audit against UK national guidelines to assess current practice and the effectiveness of an electronic tuberculosis-screening prompt.

A retrospective clinical audit was performed to assess if the British HIV Association 2011 guidelines on routine screening for tuberculosis in HIV are being implemented in a large UK urban clinic, and if a tuberculosis-screening prompt on the electronic patient record for new attendees was effective. Of 4658 patients attending during the inclusion period, 385 were newly diagnosed first-time attendees and routine tuberculosis screening was recommended in 165. Of these, only 6.1% of patients had a completed tuberculosis screening prompt, and 12.1% underwent routine tuberculosis screening. This audit represents the first published UK data on routine screening rates for tuberculosis in HIV and demonstrates low rates of tuberculosis screening despite an electronic screening prompt designed to simplify adherence to the national guideline. Reasons why tuberculosis screening rates were low, and the prompt ineffective, are unclear. A national audit is ongoing, and we await the results to see if our data reflect a lack of routine tuberculosis screening in HIV-infected patients at a national level.

Assessment of arterial elasticity among HIV-positive participants with high CD4 cell counts: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: Both HIV infection and antiretroviral therapy (ART) may increase cardiovascular disease (CVD) risk. Assessments of vascular function and structure can be used to study the pathogenesis and progression of CVD, including the effects of ART and other interventions. The objective of this report is to understand methods to assess vascular (dys)function and report our experience in the Arterial Elasticity Substudy in the Strategic Timing of AntiRetroviral Treatment (START) trial. METHODS: We review literature and analyze baseline data from the Arterial Elasticity Substudy, which estimated vascular (dys)function through analysis of the diastolic blood pressure (BP) waveform. Linear regression was used to study cross-sectional associations between baseline clinical factors and small or large arterial elasticity. RESULTS: Arterial elasticity measurement was chosen for its improved measurement reproducibility over other methodologies and the potential of small arterial elasticity to predict clinical risk. Analysis of baseline data demonstrates that small artery elasticity is impaired (lower) with older age and differs by race and between geographical regions. No HIV-specific factors studied remained significantly associated with arterial elasticity in multivariate models. CONCLUSIONS: Longitudinal analyses in this substudy will provide essential randomized data with which to study the effects of early ART initiation on the progression of vascular disease among a diverse global population. When combined with future biomarker analyses and clinical outcomes in START, these findings will expand our understanding of the pathogenesis of HIV-related CVD.

Predictors of bacterial pneumonia in Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT).

BACKGROUND AND OBJECTIVES: Bacterial pneumonia still contributes to morbidity/mortality in HIV infection despite effective combination antiretroviral therapy (cART). Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT), a trial of intermittent recombinant interleukin-2 (rIL-2) with cART vs. cART alone (control arm) in HIV-infected adults with CD4 counts ≥300cells/µL, offered the opportunity to explore associations between bacterial pneumonia and rIL-2, a cytokine that increases the risk of some bacterial infections. METHODS: Baseline and time-updated factors associated with first-episode pneumonia on study were analysed using multivariate proportional hazards regression models. Information on smoking/pneumococcal vaccination history was not collected. RESULTS: IL-2 cycling was most intense in years 1-2. Over ≈7 years, 93 IL-2 [rate 0.67/100 person-years (PY)] and 86 control (rate 0.63/100 PY) patients experienced a pneumonia event [hazard ratio (HR) 1.06; 95% confidence interval (CI) 0.79, 1.42; P=0.68]. Median CD4 counts prior to pneumonia were 570cells/µL (IL-2 arm) and 463cells/µL (control arm). Baseline risks for bacterial pneumonia included older age, injecting drug use, detectable HIV viral load (VL) and previous recurrent pneumonia; Asian ethnicity was associated with decreased risk. Higher proximal VL (HR for 1 log(10) higher VL 1.28; 95% CI 1.11, 1.47; P<0.001) was associated with increased risk; higher CD4 count prior to the event (HR per 100 cells/µL higher 0.94; 95% CI 0.89, 1.0; P=0.04) decreased risk. Compared with controls, the hazard for a pneumonia event was higher if rIL-2 was received <180 days previously (HR 1.66; 95% CI 1.07, 2.60; P=0.02) vs.≥180 days previously (HR 0.98; 95% CI 0.70, 1.37; P=0.9). Compared with the control group, pneumonia risk in the IL-2 arm decreased over time, with HRs of 1.41, 1.71, 1.16, 0.62 and 0.84 in years 1, 2, 3-4, 5-6 and 7, respectively. CONCLUSIONS: Bacterial pneumonia rates in cART-treated adults with moderate immunodeficiency are high. The mechanism of the association between bacterial pneumonia and recent IL-2 receipt and/or detectable HIV viraemia warrants further exploration.

Evaluation of Subcutaneous Proleukin (interleukin-2) in a Randomized International Trial (ESPRIT): geographical and gender differences in the baseline characteristics of participants.

BACKGROUND: ESPRIT, is a phase III, open-label, randomized, international clinical trial evaluating the effects of subcutaneous recombinant interleukin-2 (rIL-2) plus antiretroviral therapy (ART) versus ART alone on HIV-disease progression and death in HIV-1-infected individuals with CD4+ T-cells > or =300 cells/microL. OBJECTIVES: To describe the baseline characteristics of participants randomized to ESPRIT overall and by geographic location. METHOD: Baseline characteristics of randomized participants were summarized by region. RESULTS: 4,150 patients were enrolled in ESPRIT from 254 sites in 25 countries. 41%, 27%, 16%, 11%, and 5% were enrolled in Europe, North America, South America, Asia, and Australia, respectively. The median age was 40 years, 81% were men, and 76%, 11%, and 9% were Caucasian, Asian, and African American or African, respectively. 44% of women enrolled (n = 769) were enrolled in Thailand and Argentina. Overall, 55% and 38% of the cohort acquired HIV through male homosexual and heterosexual contact, respectively. 25% had a prior history of AIDS-defining illness; Pneumocystis jirovecii pneumonia, M. tuberculosis, and esophageal candida were most commonly reported. Median nadir and baseline CD4+ T-cell counts were 199 and 458 cells/muL, respectively. 6% and 13% were hepatitis B or C virus coinfected, respectively. Median duration of antiretroviral therapy (ART) was 4.2 years; the longest median duration was in Australia (5.2 years) and the shortest was in Asia (2.3 years). 17%, 13%, and 69% of participants began ART before 1995, between 1996 and 1997, and from 1998 onward, respectively. 86% used ART from two or more ART classes, with 49% using a protease inhibitor-based regimen and 46% using a nonnucleoside reverse transcriptase inhibitor-based regimen. 78% had plasma HIV RNA below detection (<500 cp/mL). CONCLUSION: ESPRIT has enrolled a diverse population of HIV-infected individuals including large populations of women and patients of African-American/African and Asian ethnicity often underrepresented in HIV research. As a consequence, the results of the study may have wide global applicability.

Post-kala-azar dermal leishmaniasis due to Leishmania infantum in a human immunodeficiency virus type 1-infected patient.

We report the first case of post-kala-azar dermal leishmaniasis due to Leishmania infantum in a human immunodeficiency virus type 1-infected patient in Australia. Molecular characterization of the isolate was performed using PCR restriction fragment length polymorphism targeting both repetitive sequences from Leishmania nuclear DNA and repetitive kinetoplast DNA minicircles for species differentiation.

Novel deletion of HIV type 1 reverse transcriptase residue 69 conferring selective high-level resistance to nevirapine.

A novel deletion of residue 69 of the HIV-1 reverse transcriptase (RT) gene was detected in combination with mutations V75I/V and F77L/F in a patient with partial virological response to several antiretroviral drug regimens, including stavudine (D4T), didanosine (DDI), lamivudine (3TC), saquinavir (SQV), and nevirapine (NVP). Longitudinal analysis of samples revealed that this deletion emerged upon reinitiation DDI/D4T therapy following a toxicity-induced short discontinuation of all antiretrovirals. Analysis of the resistance phenotype showed a greater than 62-fold increase of the IC50 of NVP, but no significant change in sensitivity to other single nonnucleoside reverse transcriptase inhibitors (NNRTIs). The mutated virus showed only a moderately reduced sensitivity to DDI (6.7-fold) and D4T (4.8 fold). In a subsequent sample 3 months later additional RT mutations were found, including A62V, Y188L, and Q151M, conferring high-level cross-resistance to multiple nucleoside analogs. Our findings provide evidence that the deletion of RT residue 69 selectively confers high-level NVP resistance.

Immunomodulators as adjunctive therapy for HIV-1 infection.

BACKGROUND: There is renewed interest in the use of immunotherapy as an adjunct to antiretrovirals (ART) in the treatment of HIV disease. Most work has been performed on interleukin-2 (IL-2). There is considerable evidence from numerous phase II studies that intermittent dosing of subcutaneous IL-2 plus antiretroviral therapy (ART) produces a sustainable rise in the CD4(+) T-lymphocyte count which exceeds that which can be achieved using ART alone, without any adverse effect on plasma HIV RNA. However, the immunological competency and therefore clinical impact of this expanded CD4(+) T cell pool is yet to be established; this question is the focus of two large clinical end-point studies, ESPRIT and SILCAAT. OBJECTIVE: Prior to the establishment of ESPRIT, four 'Vanguard' studies were undertaken; the UK Vanguard examined the safety and virological/immunological aspects of intermittent subcutaneous IL-2 without the use of ART in HIV-1 ART naïve patients with a baseline CD4(+) T cell count of > or = 350cells/mm(3). DESIGN: The UK Vanguard was an open-label, randomised study comparing subcutaneous (s/c) IL-2 at either 4.5MIU or 7.5MIU q12h for 5 days every 8 weeks versus no therapy in HIV-1-infected individuals. Primary endpoints included mean area under the curve change from baseline CD4(+) T cell count and plasma log HIV-RNA. RESULTS: Thirty six subjects were enrolled into the three arms of the UK Vanguard study. Results showed significant differences in the area under the curve (AUC) change from baseline CD4(+) T cell count (P = 0.001) and changes in mean absolute CD4(+) T cell count (P = 0.04) and no significant difference in mean AUC change from baseline plasma HIV-RNA (P = 0.48) at 24 weeks between the IL-2 and control arms respectively. The significance of these results and those from other studies on the use of IL-2 in HIV disease are discussed.

Percutaneous coronary intervention versus coronary artery bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass: a multicenter, randomized trial. Investigators of the Department of Veterans Affairs Cooperative Study #385, the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME).

BACKGROUND: Percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) are being applied to high-risk populations, but previous randomized trials comparing revascularization methods have excluded a number of important high-risk groups. OBJECTIVES: This five-year, multicenter, randomized clinical trial was designed to compare long-term survival among patients with medically refractory myocardial ischemia and a high risk of adverse outcomes assigned to either a CABG or a PCI strategy, which could include stents. METHODS: Patients from 16 Veterans Affairs Medical Centers were screened to identify myocardial ischemia refractory to medical management and the presence of one or more risk factors for adverse outcome with CABG, including prior open-heart surgery, age >70 years, left ventricular ejection fraction <0.35, myocardial infarction within seven days or intraaortic balloon pump required. Clinically eligible patients (n = 2,431) underwent coronary angiography; 781 were angiographically acceptable; 454 (58% of eligible) patients consented to random assignment between CABG and PCI. RESULTS: A total of 232 patients was randomized to CABG and 222 to PCI. The 30-day survivals for CABG and PCI were 95% and 97%, respectively. Survival rates for CABG and PCI were 90% versus 94% at six months and 79% versus 80% at 36 months (log-rank test, p = 0.46). CONCLUSIONS: Percutaneous coronary intervention is an alternative to CABG for patients with medically refractory myocardial ischemia and a high risk of adverse outcomes with CABG.

Competitive NMDA receptor antagonists and spinal-cord ischemia.

Ischemic neuronal death is associated with excitatory amino acid (EAA) release. Their action is mediated by N-methyl-D-aspartate (NMDA) receptors. Blockade of the receptors before the ischemic insult can decrease neuronal damage. Accordingly, we investigated the protective effect during spinal cord ischemia of two competitive antagonists, 4-(3-phosphonopropyl)-2-piperazine-carboxylic acid (CPP) and cis-4-(phosphonomethyl)-2-piperidine-carboxylic acid (CGS). Male Sprague-Dawley rats underwent intrathecal administration of 10 microL saline, CGS, and CPP 10 mM solutions, in a randomized blinded fashion, and were subjected to balloon occlusion of the thoracic aorta. Proximal aortic pressure was lowered to a mean of 40 mm Hg by partial exsanguination. In the acute protocol, 21 rats divided in 3 groups of 7 (saline, CPP, and CGS) were used to calculate the aortic occlusion time (AOT) resulting in paraplegia in 50% of animals (P50). In the chronic study, 24 rats divided in 4 groups of 6 (saline, CPP, CGS, sham) underwent 12-min occlusion. The chronic animals were scored daily for 28 days and submitted to histology of the cord. In the acute study, the P50 of CGS (10 min 48 s) and CPP (11 min 11 s) was longer than saline (10 min 27 s). In the chronic groups, analysis of variance of neurologic (p = .66) and histologic (p = .66) scores did not disclose differences between CGS, CPP, and saline. In conclusion, blockade of NMDA receptors with CPP or CGS may afford some protection for durations of occlusion around the P50, but it is not beneficial when ischemic injury is more protracted.

Heterotopic pancreas of the esophagus masquerading as Boerhaave's syndrome.

Heterotopic pancreas (HP) of the esophagus is rare. We report a patient with HP of the esophagus and review the presentation, treatment, and results of the nine previously reported cases. Two patients had cancer. This high incidence raises concerns that HP of the esophagus may be premalignant. Because surveillance endoscopy is not possible, all known or suspected esophageal HP should be treated surgically.

A multicenter, randomized trial of percutaneous coronary intervention versus bypass surgery in high-risk unstable angina patients. The AWESOME (Veterans Affairs Cooperative Study #385, angina with extremely serious operative mortality evaluation) investigators from the Cooperative Studies Program of the Department of Veterans Affairs.

This multicenter, prospective randomized trial was designed to test the hypotheses that percutaneous coronary intervention (PCI) is a safe and effective alternative to coronary artery bypass grafting (CABG) for patients with refractory ischemia and high risk of adverse outcomes. As a comparison of revascularization strategies, the trial specifically allows surgeons and interventionists to use new techniques as they become clinically available. After 42 months of this 72-month trial, 17,624 patients have been screened and 2022 met eligibility requirements: 341 have been randomized to either CABG or PCI, and the remaining 1681 are being prospectively followed in a registry. The 3-year overall survival of patients in the registry and randomized trial is comparable. To enhance accrual into the randomized trial, site visits were conducted, a few low-accruing hospitals were put on probation and/or replaced, eligibility criteria were reviewed at annual meetings of investigators, and the accrual period was extended by 1 year. These data demonstrate that a prospective randomized trial and registry of coronary revascularization for medically refractory high-risk patients is feasible.

Retrograde perfusion of the spinal cord during aortic crossclamping: initial observations in the swine model.

BACKGROUND: Retrograde perfusion has emerged as a useful technique for the preservation of the heart and brain when arterial circulation is interrupted. Herein, this study was designed to test the hypothesis that retrograde perfusion of the azygos vein is sufficient to maintain viability of the spinal cord during aortic occlusion in the swine model. METHODS: Female swine, 17 to 22 kg, underwent left thoracotomy, creation of a shunt between the aortic arch and the azygos vein, and aortic crossclamping for 60 minutes: the shunt was open in the retrograde perfusion group (n = 5) and closed in the control group (n = 4). The animals were evaluated for neurologic function for 8 days and killed. Spinal cords were processed for histologic examination. Additional animals underwent left thoracotomy and injection of a casting solution in the azygos vein (n = 2), left thoracotomy and angiography of the azygos vein (n = 2), and a compartmentalization procedure to separate the azygos vein from the caval system followed by angiography (n = 2). RESULTS: Differences in the neurologic (2-sample t test, P =.11) and histologic (2-sample t test, P =.65) scores of retrograde perfusion and control groups were likely due to chance. Casting and angiography groups showed extensive collaterals between azygos and caval systems, only partially interrupted by compartmentalization. CONCLUSIONS: Retrograde perfusion does not protect the spinal cord from ischemic injury. The collateral network between the azygos and caval systems prevents the oxygenated blood from reaching the cord. Surgical separation between the 2 systems was only partially successful in this study.

Selective protection of gray and white matter during spinal cord ischemic injury.

BACKGROUND: Ischemic injury in the gray matter is associated with excitatory amino acid neurotransmitters (EAA) release, and in the white matter is associated with intracellular sodium accumulation. We investigated the protective effect during spinal ischemia of the EAA antagonist, 2-carboxypiperazinyl-propylphosphonic acid (CPP), and the sodium channel blocker (2,6-dimethylphenylcarbamoylmethyl) triethylammonium bromide (QX). METHODS: Sprague-Dawley rats were randomized in four groups, received intrathecally 10 microL of saline, CPP, QX, or QX/CPP, and underwent balloon occlusion of the aorta. Proximal pressure was lowered by exsanguination. In the acute protocol, 28 rats were used to calculate the length of occlusion, resulting in paraplegia in 50% of animals (P50). In the chronic study, 60 rats underwent 11' occlusion. The chronic animals were scored daily for 28 days and submitted to cord histology. RESULTS: The P50 of QX (11'22") and QX/CPP (11'54") were longer than saline (10'39"), suggesting a beneficial effect. Neurologic scores of all treatment groups (p = 0.0001) and histologic scores of CPP (p = 0.003) and QX/CPP (p = 0.002) were better than saline. CONCLUSIONS: Protection of spinal cord during ischemia can be achieved with intrathecal administration of selective agents directed to the gray and white matter.

Primary mediastinal malignancies: findings in 219 patients.

The purpose of this study was to determine the demographics, histology, methods of treatment, and survival in primary mediastinal malignancies. We did a retrospective review of the statewide New Mexico Tumor Registry for all malignant tumors treated between January 1, 1973 and December 31, 1995. Benign tumors and cysts of the mediastinum were excluded. Two hundred nineteen patients were identified from a total of 110,284 patients with primary malignancies: 55% of tumors were lymphomas, 16% malignant germ cell tumors, 14% malignant thymomas, 5% sarcomas, 3% malignant neurogenic tumors, and 7% other tumors. There were significant differences in gender between histologies (P < 0.001). Ninety-four percent of germ cell tumors occurred in males, 66% of neurogenic tumors were in females; other tumors occurred in males in 58% of cases. There were also significant differences in ages by histology (P < 0.001). Neurogenic tumors were most common in the first decade, lymphomas and germ cell tumors in the second to fourth decades, and lymphomas and thymomas in patients in their fifth decades and beyond. Stage at presentation (P = 0.001) and treatment (P < 0.001) also differed significantly between histologic groups. Five-year survival was 54% for lymphomas, 51% for malignant germ cell tumors, 49% for malignant thymomas, 33% for sarcomas, 56% for neurogenic tumors, and 51% overall. These survival rates were not statistically different (P > 0.50). Lymphomas, malignant germ cell tumors, and thymomas were the most frequently encountered malignant primary mediastinal neoplasms in this contemporary series of patients. Demographics, stage at presentation, and treatment modality varied significantly by histology. Despite these differences, overall five-year survival was not statistically different.

Catastrophic hemorrhage on sternal reentry: still a dreaded complication?

BACKGROUND: To define the incidence of catastrophic hemorrhage (CH) during reoperations, the experience of the University of New Mexico was reviewed and compared with the practice of surgeons contacted by questionnaire. METHODS: At the University of New Mexico, 610 reoperations were reviewed and 210 deemed high risk because of multiple reoperation, aneurysm, patent grafts, chamber's enlargement, conduit or previous mediastinitis. In the questionnaire, we asked about reentry technique, occurrence and outcome of CH, and precautions for high-risk patients. RESULTS: At the University of New Mexico there were 4 CH with 1 death, and in the questionnaire there were 2,046 CH with 392 deaths. Our rate per surgeon was lower than that of the questionnaire. Rate of CH according to the saw was 2.09 for reciprocating, 2.0 for sagittal, and 1.74 for stryker in the questionnaire. Our rate was lower (0.65) with a micro sagittal saw. High-risk category predicted CH during sternotomy (p = 0.01) but only conduit (p = 0.005) was significant by univariate analysis. CONCLUSIONS: The risk of CH could be as high as 1%. The sagittal micro oscillating saw is the safest reported to date. Presence of a conduit increases the risk by 2.5 fold.

Mediastinitis without antecedent surgery.

The study evaluates the results of aggressive surgical treatment for mediastinitis without antecedent surgery, after retrospectively reviewing all patients with mediastinitis, excluding patients with prior cardiac, esophageal or mediastinal operations, treated between June 1, 1992 and August 1, 1996. 8 patients were treated. 7 were male, mean age was 58 years. The etiology was Boerhaave's syndrome in 4, iatrogenic injury in 2 and descending necrotizing mediastinitis in 2 patients. The mean number of operations was 2.5. The initial operation was through thoracotomy in 5 patients and sternotomy in 2 patients. 4 patients underwent neck drainage, 1 as primary treatment and 3 combined with transthoracic drainage. 1 patient received laparotomy. Mean hospitalization was 52 days (excluding 1 death). Complications included mechanical ventilation greater than 48 hours in 7 patients, 2 or more operations in 5 patients, multisystem organ failure in 5 patients and other complications in 6 patients. Death occurred in one patients. Mediastinitis without antecedent surgery is associated with significant morbidity, however, with aggressive surgical drainage 87% of patients survived.