Pulmonary cryptococcosis in non-AIDS patients

OBJECTIVE: To investigate the clinical features, management, and prognosis of pulmonary cryptococcosis in non-acquired immunodeficiency syndrome (AIDS) patients. METHOD: 24 cases of pulmonary cryptococcosis with accurate pathological diagnosis were retrospectively studied. RESULTS: 15 male patients and nine female patients were diagnosed at the first affiliated hospital of Sun Yat-sen University from November 1999 to November 2011. The mean age at the time of diagnosis was 44.2 ± 11.3 years (range: 24 to 65 years). Among these patients, 13 had other comorbidities. 15 were symptomatic and the other nine were asymptomatic. The most common presenting symptoms were cough, chest tightness, expectoration, and fever. None had concurrent cryptococcal meningitis. The most frequent radiologic abnormalities on chest computed tomography (CT) scans were solitary or multiple pulmonary nodules, and masses or consolidations, and most lesions were located in the lower lobes. All patients had biopsies for the accurate diagnosis. Among the 24 patients, nine patients underwent surgical resections (eight had pneumonectomy via thoracotomy and one had a pneumonectomy via thoracoscopy). Five of the patients who underwent surgery also received antifungal drug therapy (fluconazole) for one to three months after the surgery. The other 15 only received antifungal drug therapy (fluconazole or voriconazole) for three to six months (five patients are still on therapy). The follow-up observation of 19 patients who had already finished their treatments lasted from two to 11 years, and there was no relapse, dissemination, or death in any of these patients. CONCLUSION: Non-AIDS patients with pulmonary cryptococcosis have a good prognosis with appropriate management.

Pulmonary cryptococcosis in non-AIDS patients.

OBJECTIVE: To investigate the clinical features, management, and prognosis of pulmonary cryptococcosis in non-acquired immunodeficiency syndrome (AIDS) patients. METHOD: 24 cases of pulmonary cryptococcosis with accurate pathological diagnosis were retrospectively studied. RESULTS: 15 male patients and nine female patients were diagnosed at the first affiliated hospital of Sun Yat-sen University from November 1999 to November 2011. The mean age at the time of diagnosis was 44.2±11.3 years (range: 24 to 65 years). Among these patients, 13 had other comorbidities. 15 were symptomatic and the other nine were asymptomatic. The most common presenting symptoms were cough, chest tightness, expectoration, and fever. None had concurrent cryptococcal meningitis. The most frequent radiologic abnormalities on chest computed tomography (CT) scans were solitary or multiple pulmonary nodules, and masses or consolidations, and most lesions were located in the lower lobes. All patients had biopsies for the accurate diagnosis. Among the 24 patients, nine patients underwent surgical resections (eight had pneumonectomy via thoracotomy and one had a pneumonectomy via thoracoscopy). Five of the patients who underwent surgery also received antifungal drug therapy (fluconazole) for one to three months after the surgery. The other 15 only received antifungal drug therapy (fluconazole or voriconazole) for three to six months (five patients are still on therapy). The follow-up observation of 19 patients who had already finished their treatments lasted from two to 11 years, and there was no relapse, dissemination, or death in any of these patients. CONCLUSION: Non-AIDS patients with pulmonary cryptococcosis have a good prognosis with appropriate management.

Monoclonal antibodies anti-TGFß1 and anti-VEGF inhibit the experimental pleurodesis induced by silver nitrate.

BACKGROUND: The mechanisms underlying pleural inflammation and pleurodesis are poorly understood. We hypothesized that the cytokines transforming growth factor ß (TGFß1) and vascular endothelial growth factor (VEGF) play a major role in pleurodesis after intrapleural silver nitrate (SN) injection. METHOD: Forty rabbits received intrapleurally 0.5% SN alone or 0.5% SN + anti-TGFß1, anti-IL-8, or anti-VEGF. After 28 days, the animals were euthanized and macroscopic pleural adhesions, microscopic pleural fibrosis, and collagen deposition were analyzed for characterization of the degree of pleurodesis (scores 0-4). RESULTS: Scores of pleural adhesions, pleural fibrosis, total collagen, and thin collagen fibers deposition after 28 days were significantly lower for 0.5% SN + anti-TGFß1 and 0.5% SN + anti-VEGF. Significant correlations were found between macroscopic adhesion and microscopic pleural fibrosis with total collagen and thin collagen fibers. CONCLUSIONS: We conclude that both TGFß1 and VEGF, but not IL-8, mediate the pleural inflammatory response and pleurodesis induced by SN.

Low doses of silver nitrate induce pleurodesis with a limited systemic response.

BACKGROUND AND OBJECTIVE: Both talc and 0.5% silver nitrate have been shown to induce effective pleurodesis. However, acute adverse systemic inflammatory effects have been described with both agents. The aim of this study was to assess in rabbits the systemic effects associated with a new technique of pleurodesis using repeated low doses of 0.1% silver nitrate. METHODS: Rabbits were injected intrapleurally through a chest tube with 0.1% silver nitrate at 0, 24 and 48 h. Other groups received a single injection of 0.5% silver nitrate or 400 mg/kg of talc. Blood samples were collected at 24, 48 and 72 h, and at 7 days, and cytological and biochemical measurements were performed. After 28 days, the presence of macroscopic pleural adhesions and microscopic pleural fibrosis in the pleural cavity were evaluated. RESULTS: Both talc and 0.5% silver nitrate caused significant increases in blood neutrophils, serum LDH, IL-8, transforming growth factor-beta and CRP in comparison with control at almost all time points, whereas sequential doses of 0.1% silver nitrate only increased LDH and CRP in the first 24 h and transforming growth factor-beta at all time points. All groups showed efficient pleurodesis, with no differences in pleural adhesions or fibrosis. CONCLUSIONS: Sequential doses of 0.1% silver nitrate produced efficient pleurodesis in rabbits, with a low systemic inflammatory response in comparison with 400 mg/kg of talc or 0.5% silver nitrate.

Pleurodesis: a novel experimental model.

BACKGROUND AND OBJECTIVE: The experimental model of pleurodesis in rabbits has been useful in understanding the pathophysiology of the pleural inflammatory injury induced by several sclerosing agents. However, restrictions on the use of rabbits in laboratory investigation are making this model less accessible. The aim of this study was to present a new experimental model of pleurodesis in mice using talc or silver nitrate. METHODS: Four groups of 10 C57BL/6 mice received talc 2 or 4 mg/g in 0.5 mL saline, or 0.025% or 0.05% silver nitrate in 0.5 mL H(2)O. After 28 days the animals were sacrificed, and the pleural cavity was opened and evaluated for evidence of macroscopic pleural adhesions and haemothorax (scores 0-4), atelectasis (scores 0-2), and microscopic pleural and alveolar inflammation and fibrosis (scores 0-4). Statistical analysis used ANOVA. RESULTS: Silver nitrate 0.05% produced a more effective pleurodesis in mice than did 0.025% silver nitrate or talc 4 mg/g, with significant higher scores for pleural adhesions, microscopic pleural inflammation and fibrosis. Haemothorax, atelectasis, and microscopic alveolar inflammation and fibrosis were negligible in both groups. CONCLUSIONS: Both talc 4 mg/g and 0.05% silver nitrate produced an efficient pleurodesis in this experimental model in mice. This new model may overcome the restrictions on the use of large- and medium-sized animals in laboratory investigation and may open new fields of investigation with knockout mice.

Derrame Pelural / It spills Pelural

Nota del Editor: la diferenciación entre exudados y transudados constituye el primer paso en el diagnóstico diferencial de los derrames pleurales, desde 1972 el Doctor Richard W. Light propuso unos parámetros como guía para tal diferenciación.Medicina & Laboratorio ha recibido la autorización del propio autor, para la traducción del texto con el fin de que sea una herramienta de consulta en el manejo del ®derrame pleural¼, de vital importancia para la comunidad médica.

Intrapleural low-dose silver nitrate elicits more pleural inflammation and less systemic inflammation than low-dose talc.

STUDY OBJECTIVES: Several systemic effects have been described after talc pleurodesis. The aim of this study was to assess the systemic response induced by low, nonpleurodesis-inducing doses of talc and silver nitrate in an experimental model in rabbits. DESIGN: Groups of six rabbits were injected intrapleurally with talc, 100 mg/kg or 400 mg/kg, and silver nitrate, 0.1% or 0.5%. After 6, 24, or 48 h, samples of blood and pleural fluid were collected and assayed for leukocytes, percentage of neutrophils, lactate dehydrogenase, interleukin-8, and vascular endothelial growth factor (VEGF) levels. Preinjection blood samples were used as normal blood controls. MEASUREMENTS AND RESULTS: Silver nitrate 0.1% induced a more intense pleural inflammation than that produced by talc 100 mg/kg. In contrast, talc 100 mg/kg induced a more pronounced acute systemic response with higher values of WBCs and neutrophils, whereas silver nitrate 0.1% produced no significant increases in leukocytes or neutrophils. The serum interleukin-8 and VEGF levels increased in all groups, and decreased with time only in the silver nitrate 0.1% group. The highest serum VEGF levels were observed in the talc 100 mg/kg group. CONCLUSIONS: In conclusion, 0.1% silver nitrate produced an intense pleural inflammatory response with a less evident systemic response in comparison to 0.5% silver nitrate and talc 100 mg/kg or 400 mg/kg.

Prospective randomized trial of silver nitrate vs talc slurry in pleurodesis for symptomatic malignant pleural effusions.

STUDY OBJECTIVES: To compare the efficacy and the safety of talc slurry and silver nitrate (SN) in the treatment of symptomatic malignant pleural effusions. PATIENTS AND METHODS: Sixty patients were enrolled into the study, and all received a chest tube (26F or 28F) that was placed using local anesthesia. The patients were randomized to receive either 5 g talc diluted to a total volume of 50 mL with saline solution or 20 mL 0.5% SN through the chest tube. Patients were clinically evaluated before and after treatment regarding pain, and were evaluated at monthly intervals with respect to the effectiveness of pleurodesis. Eleven patients did not return for their 30-day follow-up visit and were excluded from further analysis. Pleurodesis therapy was considered to be successful if there was no recurrence of the effusion. The patients who did not have a pleurodesis at one visit were excluded from subsequent visits. RESULTS: Forty-nine patients returned at 30 days for follow-up, including 24 patients who received SN and 25 who received talc. The groups were similar in age (p = 0.23), sex (p = 0.70), Karnofsky index (p = 0.94), and pathology (p = 0.68). After the induction of pleurodesis, neither the total mean (+/- SE) fluid drainage (SN, 901 +/- 125 mL; talc, 766 +/- 74 mL; p = 0.36) nor the level of pain (SN, 2.58 +/- 0.26; talc, 2.62 +/- 0.30; p = 0.91) differed significantly between the groups, and no patient in either group developed ARDS. The mean number of days spent in the hospital was nearly identical (SN group, 3.7 +/- 0.15 days; talc group, 3.6 +/- 0.13 days; p = 0.47). Both SN and talc were effective agents. Thirty days after the procedure, 23 of 24 patients (96%) who had received SN and 21 of 25 patients (84%) who had received talc showed an effective pleurodesis (p = 0.35). Similar results were observed after 60 days (SN group, 18 of 18 patients [100%]; talc group, 13 of 13 patients [100%]; p = > 0.99), 90 days (SN group, 16 of 16 patients [100%]; talc, 8 of 9 patients [89%]; p = 0.36), and 120 days (SN group, 4 of 4 patients [100%]; talc group, 4 of 4 patients [100%]; p > 0.99). CONCLUSIONS: The present study suggests that SN is an effective agent for producing a pleurodesis. In the present study, SN showed a tendency to be more effective than talc, but the power of the test to detect a significance difference was low in this small group of patients. The side effects of 0.5% SN appear to be minimal, but since only a small number of patients received SN and nearly 20% of the patients were lost to follow-up, significant long-term side effects cannot be excluded. Since SN appears to be as effective as talc, and since there is no evidence that it induces ARDS as has been reported with talc, it should be considered as an alternative to talc for the production of a pleurodesis.

Talc and silver nitrate induce systemic inflammatory effects during the acute phase of experimental pleurodesis in rabbits.

STUDY OBJECTIVE: s: To determine whether talc (TL) and silver nitrate (SN), two effective pleurodesis agents, induce a systemic inflammatory response in the acute phase of experimental pleurodesis in rabbits. DESIGN: Samples of blood and pleural fluid were collected after 6, 24, and 48 h from rabbits injected intrapleurally with 3 mL saline solution, TL (400 mg/kg), or 0.5% SN, and were assayed for WBC count, percentage of neutrophils, and levels of lactate dehydrogenase (LDH), interleukin (IL)-8, and vascular endothelial growth factor (VEGF). The pleural liquid production was compared in the three different groups. A sample of blood collected from animals preinjection was used as the control. RESULTS: At 6 h after pleural injection, the mean blood WBC count and percentage of neutrophils were significantly elevated in the TL group, whereas the mean LDH and IL-8 levels were significantly increased in the SN group. VEGF was undetectable in the preinjection serum and saline solution-injected animals, but was increased in the serum after the pleural injection of both TL and SN to a comparable degree. SN elicited a more intense acute pleural inflammation reaction than did TL, with higher WBC count and IL-8 levels found in the pleural fluid, mainly within the first 6 h. LDH and VEGF levels, and pleural liquid production were also higher for SN, and they increased with time. CONCLUSIONS: In the acute phase of pleural injection, TL induced a transient increase in blood WBC count and percentage of neutrophils, while SN induced increases in blood LDH and IL-8 levels. Both TL and SN induced significant increases in blood VEGF levels. SN induced an earlier and more intense acute pleural inflammation than TL. Pleural liquid VEGF levels were higher after SN injection and increased, as did pleural liquid production. These findings suggest that the intrapleural injection of TL and SN produce a systemic inflammatory response that may have a role in the pathogenesis of fever and ARDS, which occur with pleurodesis.

Acute pleuropulmonary complications detected by computed tomography following myocardial revascularization.

INTRODUCTION: Pleuropulmonary changes are common following coronary artery bypass grafting surgery performed with a saphenous vein graft, with or without an internal mammary artery. The presence of atelectasis or pleural effusions reflects the thoracic trauma. PURPOSE: To define the postoperative incidence of changes in the lung and in the pleural space and to evaluate the influence of the trauma. METHODS: Thirty patients underwent elective coronary artery bypass grafting surgery (8 saphenous vein grafts and 22 saphenous vein grafts and internal mammary artery grafts with pleurotomy). Chest tubes in the left pleural space were used in all internal mammary artery patients. On the second (day 2) and seventh (day 7) postoperative day, patients underwent a computed tomography, and pleural effusions were rated as follows: grade 0 = no fluid to grade 4 = fluid in more than 75% of the hemithorax. Atelectasis was rated as follows: laminar = 1, segmental = 3, and lobar = 10 points. RESULTS: All patients had pleural effusion or atelectasis. Between day 2 and day 7, the number of patients with effusions or atelectasis on the right side decreased (P < 0.05). The incidence of effusions on day 2 in the saphenous vein graft group (87.5%) was higher (P < 0.05) than in the internal mammary artery group (52.3%). The incidence of atelectasis in the lower right lobe decreased (P < 0.05) from 86.7% (day 2) to 26.7% (day 7). The degree of atelectasis in both sides did not differ on day 2 (P = 0.42) but did on day 7 (P < 0.0001). There was a decrease in the atelectasis from day 2 to day 7 on the right side (P < 0.001), but not on the left (P = 0.21). On day 2 there was a relationship between atelectasis and effusion on the right (P = 0.04), but not on the left (P = 0.113). CONCLUSION: The present series demonstrates that there is a high incidence of both minimal pleural effusion and atelectasis after coronary artery bypass grafting surgery, which drops on the right side from day 2 to day 7 post surgery. Factors that contribute to the persistence of changes on the left side include the thoracic trauma and the presence of chest tubes and pericardial effusion.

Iodopovidone pleurodesis for recurrent pleural effusions.

STUDY OBJECTIVE: Chemical pleurodesis may be the best available treatment for recurrent and troublesome pleural effusions when the underlying cause cannot be corrected. A wide variety of pleural irritants have been used, but the search for the ideal agent for pleurodesis continues. The purpose of our study is to evaluate the efficacy and safety of iodopovidone as an agent for pleurodesis in patients with recurrent pleural effusion. DESIGN AND SETTING: Multicenter prospective study. INTERVENTION: The pleurodesis solution consisted of a mixture of 20 mL 10% iodopovidone and 80 mL normal saline solution. It was infused and left in the pleural cavity for 2 h. In 12 patients, pleurodesis was performed through a tube thoracostomy, and in the remaining 40 patients it was carried out at the end of diagnostic thoracoscopy. RESULTS: Fifty-two patients were included, with a mean (+/- SEM) age of 56.6 +/- 1.84 years. Eighty-five percent of the cases were related to a malignant neoplasm. A complete response, with no reaccumulation of fluid during follow-up, was obtained in 50 patients (96.1%). A second procedure was successful in the two remaining patients. Three patients (5.8%) experienced intense pleuritic pain and systemic hypotension after the instillation of the sclerosing agent. They recovered without incident. The mean length of follow-up was 13 +/- 1.46 months, with a median of 8.5 months. There were no 30-day postoperative deaths. CONCLUSIONS: Iodopovidone is an effective, safe, readily available, and inexpensive alternative to achieve chemical pleurodesis in cases of recurrent, incapacitating effusions, regardless of etiology.

Acute pleuropulmonary complications detected by computed tomography following myocardial revascularization

INTRODUCTION: Pleuropulmonary changes are common following coronary artery bypass grafting surgery performed with a saphenous vein graft, with or without an internal mammary artery. The presence of atelectasis or pleural effusions reflects the thoracic trauma. PURPOSE: To define the postoperative incidence of changes in the lung and in the pleural space and to evaluate the influence of the trauma. METHODS: Thirty patients underwent elective coronary artery bypass grafting surgery (8 saphenous vein grafts and 22 saphenous vein grafts and internal mammary artery grafts with pleurotomy). Chest tubes in the left pleural space were used in all internal mammary artery patients. On the second (day 2) and seventh (day 7) postoperative day, patients underwent a computed tomography, and pleural effusions were rated as follows: grade 0 = no fluid to grade 4 = fluid in more than 75 percent of the hemithorax. Atelectasis was rated as follows: laminar = 1, segmental = 3, and lobar = 10 points. RESULTS: All patients had pleural effusion or atelectasis. Between day 2 and day 7, the number of patients with effusions or atelectasis on the right side decreased (P < 0.05). The incidence of effusions on day 2 in the saphenous vein graft group (87.5 percent) was higher (P < 0.05) than in the internal mammary artery group (52.3 percent). The incidence of atelectasis in the lower right lobe decreased (P < 0.05) from 86.7 percent (day 2) to 26.7 percent (day 7). The degree of atelectasis in both sides did not differ on day 2 (P = 0.42) but did on day 7 (P < 0.0001). There was a decrease in the atelectasis from day 2 to day 7 on the right side (P < 0.001), but not on the left (P = 0.21). On day 2 there was a relationship between atelectasis and effusion on the right (P = 0.04), but not on the left (P = 0.113). CONCLUSION: The present series demonstrates that there is a high incidence of both minimal pleural effusion and atelectasis after coronary artery bypass grafting surgery, which drops on the right side from day 2 to day 7 post surgery. Factors that contribute to the persistence of changes on the left side include the thoracic trauma and the presence of chest tubes and pericardial effusion

The effect of corticosteroids on pleurodesis induced by doxycycline in rabbits.

STUDY OBJECTIVE: To determine if the administration of systemic corticosteroids diminishes the effectiveness of the pleurodesis induced by the intrapleural injection of doxycycline. STUDY DESIGN: Thirty New Zealand white male rabbits were classified into three groups (n = 10 rabbits), all of which received doxycycline, 10 mg/kg intrapleurally, in a volume of 2 mL. Rabbits in the control group received only the intrapleural injection of doxycycline; the steroid-once group received triamcinolone, 0.8 mg/kg IM, 24 h before the intrapleural injection; and the steroid-weekly group received triamcinolone, 0.8 mg/kg IM, 24 h before the intrapleural injection and weekly over the next 3 weeks. All rabbits had a chest tube placed before the intrapleural administration of doxycycline and underwent pleural fluid aspiration twice daily. The rabbits were killed after 28 days, and the pleura and lungs were examined macroscopically and microscopically. RESULTS: The administration of corticosteroids resulted in both a significant decrease in the macroscopic adhesion score (p < 0.001) and a tendency toward a decreased microscopic fibrosis score (p = 0.056) after 28 days. Animals receiving weekly corticosteroid injections had lower scores than animals receiving only one injection. CONCLUSION: This study demonstrates that the administration of corticosteroids (triamcinolone, 0.8 mg/kg) 24 h before the intrapleural injection of doxycycline, 10 mg/kg, decreases the effectiveness of pleurodesis in rabbits. Weekly injections decreased the effectiveness even more. If these results can be extrapolated to humans, efforts should be made to minimize the administration of exogenous corticosteroids when pleurodesis is attempted.