Projected Time for the Elimination of Cervical Cancer Under Various Intervention Scenarios: Age-Period-Cohort Macrosimulation Study.

BACKGROUND: The World Health Organization aims for the global elimination of cervical cancer, necessitating modeling studies to forecast long-term outcomes. OBJECTIVE: This paper introduces a macrosimulation framework using age-period-cohort modeling and population attributable fractions to predict the timeline for eliminating cervical cancer in Taiwan. METHODS: Data for cervical cancer cases from 1997 to 2016 were obtained from the Taiwan Cancer Registry. Future incidence rates under the current approach and various intervention strategies, such as scaled-up screening (cytology based or human papillomavirus [HPV] based) and HPV vaccination, were projected. RESULTS: Our projections indicate that Taiwan could eliminate cervical cancer by 2050 with either 70% compliance in cytology-based or HPV-based screening or 90% HPV vaccination coverage. The years projected for elimination are 2047 and 2035 for cytology-based and HPV-based screening, respectively; 2050 for vaccination alone; and 2038 and 2033 for combined screening and vaccination approaches. CONCLUSIONS: The age-period-cohort macrosimulation framework offers a valuable policy analysis tool for cervical cancer control. Our findings can inform strategies in other high-incidence countries, serving as a benchmark for global efforts to eliminate the disease.

Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022.

BACKGROUND & AIMS: We aimed to assess the secular trend of the global prevalence of Helicobacter pylori (H pylori) infection in adults and children/adolescents and to show its relation to that of gastric cancer incidence. METHODS: We performed a systematic review and meta-analysis to calculate overall prevalence, adjusted by multivariate meta-regression analysis. The incidence rates of gastric cancer were derived from the Global Burden of Disease Study and Cancer Incidence in Five Continents. RESULTS: Of the 16,976 articles screened, 1748 articles from 111 countries were eligible for analysis. The crude global prevalence of H pylori has reduced from 52.6% (95% confidence interval [CI], 49.6%-55.6%) before 1990 to 43.9% (95% CI, 42.3%-45.5%) in adults during 2015 through 2022, but was as still as high as 35.1% (95% CI, 30.5%-40.1%) in children and adolescents during 2015 through 2022. Secular trend and multivariate regression analyses showed that the global prevalence of H pylori has declined by 15.9% (95% CI, -20.5% to -11.3%) over the last 3 decades in adults, but not in children and adolescents. Significant reduction of H pylori prevalence was observed in adults in the Western Pacific, Southeast Asian, and African regions. However, H pylori prevalence was not significantly reduced in children and adolescents in any World Health Organization regions. The incidence of gastric cancer has decreased globally and in various countries where the prevalence of H pylori infection has declined. CONCLUSIONS: The global prevalence of H pylori infection has declined during the last 3 decades in adults, but not in children and adolescents. The results raised the hypothesis that the public health drive to reduce the prevalence of H pylori as a strategy to reduce the incidence of gastric cancer in the population should be confirmed in large-scale clinical trials.

Urban-Rural Disparity in Birth Cohort Effects on Breast Cancer Incidence.

Breast cancer is the most commonly diagnosed cancer among women worldwide. Studies have reported minimal birth cohort effects on the incidence rates of breast cancer in Western countries but have reported notable birth cohort effects in some Asian countries. The risks of breast cancer may also vary within a country. In the present study, we abstracted female invasive breast cancer data from the Taiwan Cancer Registry for the period 1997-2016. We used the age-period-cohort model to compare birth cohort effects on breast cancer incidence rates between urban and rural regions in Taiwan. We identified a notable urban-rural disparity in birth cohort effects on breast cancer incidence rates in women in Taiwan. The incidence rates in the urban regions were higher than those in the rural regions across all cohorts. However, the incidence rates rose faster in the rural regions than in the urban regions across the cohorts. The risks of breast cancer observed for women born in 1992 were approximately 22 and 11 times than those observed for women born in 1917 in rural and urban regions, respectively. The observed gap in breast cancer incidence rates between the urban and rural regions gradually disappeared across the cohorts. Accordingly, we speculate that urbanization and westernization in Taiwan may be the drivers of female breast cancer incidence rates across birth cohorts.

Birth Cohort Effects in Breast Cancer Incidence: Global Patterns and Trends.

Breast cancer is the most common neoplasm in the world among women. The age-specific incidences and onset ages vary widely between Asian and Western countries/regions. Invasive breast cancer cases among women from 1997 to 2011 were abstracted from the International Agency for Research on Cancer and the Taiwan Cancer Registry. Age-period-cohort analysis was performed to examine the trends. The cohort effect was prominent in South Korea, Taiwan, Japan, and Thailand, possibly related to the timing of westernization. The risk of breast cancer initially rose with the birth cohorts in Hong Kong and India (both former British colonies), peaked, and then declined in recent birth cohorts. Unlike other Asian countries/regions, virtually no birth cohort effect was identified in the Philippines (a Spanish colony in 1565 and the first Asian country to adopt Western cultural aspects). Moreover, an at-most negligible birth cohort effect was identified for all ethnic groups (including Asian immigrants) in the United States. This global study identified birth cohort effects in most Asian countries/regions but virtually no impact in Western countries/regions. The timing of westernization was associated with the birth cohort effect.

Forecast of a future leveling of the incidence trends of female breast cancer in Taiwan: an age-period-cohort analysis.

Breast cancer is the most common cancer among women in Taiwan. The age-standardized incidence rate has doubled in just 20 years, causing considerable concern to health professionals and the general public. This study used an ensemble of age-period-cohort models to estimate breast cancer incidence trends in Taiwan from 1997 to 2016 and project trends up to 2035. The (truncated) world standard population (World Health Organization 2000) proportions (age groups: 25-29, 30-34, …, 80-84, and older than 85 years) were used to calculate age-standardized incidence rates. The age-standardized incidence rate from 1997 (60.33/100,000 population) to 2016 (128.20/100,000 population) increased rapidly. The projection is that the increase in the age-standardized incidence will subsequently slow and exhibit a plateau in 2031 (151.32/100,000 population). From 2026 to 2035, the age-specific incidence rates for women older than 55 years old (postmenopausal breast cancer) are projected to increase with larger percentage increments for older women. A future leveling of female breast cancer incidence trends in Taiwan is anticipated. The majority of the patients with breast cancer in the future will be women aged 55 years and older. Education on lifestyle recommendations and mammography screening is required to reduce the burden of breast cancer. The results should have implications for other countries which are also confronted with the same public health problem of rapidly increasing breast cancer incidences.

Distinctive incidence patterns of follicular lymphoma in Taiwan: Implications of ethnic differences.

BACKGROUND: Follicular lymphoma (FL) is less prevalent in Asians, but detailed epidemiological analyses were not available. This study aimed to characterize the epidemiologic features of FL in Taiwan to explore the factors relevant to disease development and prognosis. METHODS: We obtained epidemiological data for Taiwanese citizens during 1990-2012 from Taiwan's National Cancer Registry Database, and the corresponding data for US Caucasians from the Surveillance, Epidemiology, and End Results Program. Changes in incidence rates were evaluated with age-period-cohort (APC) analyses. Patient outcomes were compared with 5-year relative survival rates (RS) estimates. RESULTS: Incidence rates of FL in Taiwan increased continuously during the study period (0.34 to 0.91 per 100 000 person-year from 1993-1997 to 2008-2012 in men, and from 0.29 [1993-1997] to 0.81 [2008-2012] in women), while rates in the US remained stable in both sexes, ranging between 3.73 and 3.96 in men and between 3.24 and 3.55 in women. Estimates of average annual percentage changes in incidence were significantly positive in Taiwan, but not in US Caucasians. Notably, the APC analysis identified a strong birth-cohort effect in Taiwan, corresponding to environmental alterations present during the study period. The estimated 5-year RS rates in both populations showed steady improvement, but the RS in Taiwanese patients was consistently 10% lower than in US Caucasians. CONCLUSION: A distinct increasing trend of incidence with a strong birth-cohort effect was identified in Taiwan, providing evidence of the association between environmental factors and disease development.

Sexual and bladder dysfunction in male ketamine abusers: A large-scale questionnaire study.

PURPOSE: To evaluate the prevalence of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in the illicit male ketamine abusers (KA). MATERIALS AND METHODS: The male street KAs caught by policemen and patients visiting urologic clinics were invited to answer a structured questionnaire including demographic data, illicit drug use related details (duration, frequency, dosage and abstinence status), international prostate symptoms score (IPSS), interstitial cystitis symptoms and problem index (ICSI and ICPI) and International index of erectile function (IIEF-5). Erectile dysfunction was defined as IIEF-5 ≦21. RESULTS: Finally, we included 1056 participants (993 street, 63 hospital KAs) with a mean age of 27.4 ±6.2 years. ED presented in 30.8% of all KAs. and Hospital KAs were more subject to having ED than street KAs (69.6% vs. 28.0%, p<0.01). Multi-variate analysis revealed that risk factor for male ED were age ≧30 years (OR = 1.765). Subgroup analysis on male street KAs disclosed that abstinence ≧3 months is a protective factor for ED. Lower urinary tract symptoms (ICSI+ICPI ≧12) was prevalent in KAs and multivariate analysis disclosed that significant risk factors for LUTS (ICSI+ICPI ≧12) were age ≧30 years, duration ≧24 months and co-use of other illicit drugs. CONCLUSIONS: Male ED and LUTS were frequently observed in the ketamine abusers. We suggested that street ketamine abuse should be considered in young men presented with ED and LUTS in the clinics.

Zoledronic acid infusion for lumbar interbody fusion in osteoporosis.

BACKGROUND: Clinical outcomes of intravenous (IV) infusion of zoledronic acid (ZOL) for lumbar interbody fusion surgery (LIFS) remain unknown. We investigated the efficacy of IV ZOL on clinical outcome and bone fusion after LIFS. MATERIALS AND METHODS: We retrospectively analyzed 64 patients with both degenerative lumbar spondylolisthesis and osteoporosis who underwent LIFS from January 2007 to April 2010. All patients were followed up for 2 y. Thirty-two were treated with an IV infusion of ZOL 3 d after surgery and a second injection 1 y later, and the other 32 patients did not receive ZOL. Preoperatively and every 3 mo postoperatively, oswestry disability index questionnaire and visual analog scale (VAS) scores for back and leg were compared. Preoperative and final postoperative follow-up to evaluate for subsequent compression fractures were also performed. Pedicle screw loosening, cage subsidence, and fusion rate were documented 2 y after surgery. RESULTS: At 2-y follow-up, a solid fusion was achieved in 75% of the ZOL group and only 56% of the control group. At final follow up, the incidence of final subsequent vertebral compression fractures (19% of the ZOL group and 51% of the control group, P = 0.006), pedicle screw loosening (18% of the ZOL group and 45% of the control group, P = 0.03), and cage subsidence >2 mm (28% of the ZOL group and only 54% of the control group, P = 0.04) were significantly lower in the ZOL group than in the control group. The ZOL group demonstrated improvement in VAS (for leg pain VAS, 2/10 for the ZOL group and 5/10 for the control group; for back pain VAS, 2/10 for the ZOL group and 6/10 for the control group) and oswestry disability index scores (7/25 for the ZOL group and 16/25 for the control group). CONCLUSIONS: ZOL treatment has beneficial effects on instrumented LIFS both radiographic and clinically. Thus, ZOL treatment can be recommended for osteoporosis patients undergoing LIFS.

The role of total bile acid in oral secretions in ventilator-associated pneumonia.

PURPOSE: The aim of this study was to investigate the role of inflammatory biomarkers and total bile acid (TBA) in oral secretions in the development of ventilator-associated pneumonia (VAP). MATERIALS: This prospective study was conducted in an intensive care unit. Oral secretions were collected from mechanically ventilated patients who met the selection criteria for VAP prevention protocol. The levels of interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor α, soluble intercellular adhesion molecule-1, monocyte chemoattractant protein-1, C-reactive protein, surfactant protein D, and TBA in oral secretions were measured and compared between the patients with and those without VAP. RESULTS: Thirty-nine patients with and 39 patients without VAP were studied. The levels of inflammatory biomarkers in oral secretions showed no significant difference between the 2 groups. However, the patients with VAP had significantly higher values of TBA in oral secretions than did those without VAP (median and 25th-75th interquartile range, 9.59 and 1.37-24.66 µmol/L vs 2.74 and 0.00-8.22 µmol/L; P < .003). No significant correlations were found between TBA and inflammatory biomarkers in oral secretions. CONCLUSIONS: Duodenogastroesophageal reflux as evidenced by the presence of TBA in oral secretions is common in mechanically ventilated patients and may play a role in the development of VAP.

[PEG-mediated covalent binding of VEGF to decellularized aortic valves promotes adhesion and proliferation of endothelial progenitor cells].

OBJECTIVE: To improve the biological properties of decellularized aortic valves by polyethylene glycol (PEG)-mediated covalent incorporation of vascular endothelial growth factor (VEGF). METHODS: PEG crosslinking of decellularized aortic valves were completed via a Michael-type addition reaction, followed by covalent incorporation of VEGF through another Michael-type addition reaction between the unsaturated propylene acyl of PEG and the thiol groups on cysteine residues of VEGF. The effect of VEGF incorporation was evaluated by enzyme-linked immunosorbent assay (ELISA) and immune fluorescence assay. The endothelial progenitor cells (EPCs) were seeded on decellularized aortic valves with or without these modifications, and after 10 days of culture, the valves were examined for DNA content and by hematoxylin-eosin staining and scanning electron microscopy. RESULTS: Immune fluorescence and ELISA showed that the maximal VEGF incorporation on the decellularized aortic valve reached 908.94∓0.27 pg. Compared with the unmodified valves and the valves with PEG crosslinking, decellularized aortic valves with covalent incorporation of VEGF significantly promoted the adhesion and proliferation of EPCs, which formed a confluent cell monolayer on the valve surface. CONCLUSIONS: PEG-mediated covalent incorporation of VEGF in the decellularized aortic valves improves the adhesion and proliferation of the seeded EPCs to facilitate the construction of tissue-engineered heart valves.

Male gender is a risk factor for recurrent appendicitis following nonoperative treatment.

BACKGROUND: This prospective study investigates recurrence rates and identifies predictive factors for recurrence following successful nonoperative treatment in adult patients with acute appendicitis. METHODS: Between January 2003 and December 2009, adult patients with acute appendicitis who received successful nonoperative management were enrolled. Cumulative recurrence rates were calculated using the Kaplan-Meier method. Recurrence-free curves were compared using with the log-rank test. Cox regression models were employed to identify parameters that significantly and independently predict recurrence. RESULTS: During the study period, 128 patients were enrolled. The median follow-up period was 12 months (range=1-90 months). Twenty (16%) patients developed recurrent appendicitis during follow-up. Twenty-one (16%) patients underwent interval appendectomy (IA). There was no significant difference between nonperforated (NPA) and perforated appendicitis (PA) groups with respect to recurrence rates (16% at the 9th month). Moreover, male gender was significantly associated with recurrence (HR 3.45; 95% CI, 1.15-10.39). Analytical results remained significant after excluding IA patients. CONCLUSIONS: Since the recurrence rate is similar between NPA and PA, nonoperative treatment can be used for PA patients. Roughly 20% of the adult patients selected for nonoperative treatment experienced recurrence. Males were more susceptible than females to recurrent appendicitis.

Clinical importance of bronchoalveolar lavage fluid and blood cytokines, surfactant protein D, and Kerbs von Lungren 6 antigen in idiopathic pulmonary alveolar proteinosis.

OBJECTIVE: To investigate the clinical importance of cytokines, surfactant protein D (SFTPD, formerly SP-D), and Kerbs von Lungren 6 antigen (KL-6) in bronchoalveolar lavage fluid (BALF) and blood in patients with idiopathic pulmonary alveolar proteinosis (iPAP). PARTICIPANTS AND METHODS: Patients with iPAP diagnosed by characteristic cytopathologic examination of BALF and pathologic examination of transbronchial lung biopsy specimens or open lung biopsy specimens were enrolled in the study from January 1, 1995, through June 30, 2005. To investigate the clinical importance of cytokines, SFTPD, and KL-6 in iPAP, we measured tumor necrosis factor superfamily, member 2 (TNF, formerly TNF-alpha) and interleukin (IL) 1beta in BALF and IL-6, IL-10, IL-8, chemokine (C-C motif) ligand 4 (CCL4, formerly MIP-1beta), chemokine (C-C motif) ligand 2 (CCL2, formerly MCP-1), SFTPD, and KL-6 in both BALF and blood in 15 patients with iPAP and 48 patients with interstitial lung diseases (diseased controls) (including 20 with interstitial pneumonitis associated with collagen vascular diseases, 13 with idiopathic pulmonary fibrosis, and 15 with sarcoidosis) and 20 individuals without pulmonary diseases (lung controls). RESULTS: Patients with iPAP had significantly higher levels of TNF, IL-6, IL-8, CCL4, CCL2, SFTPD, and KL-6 in BALF than did lung controls and had significantly higher levels of CCL4, CCL2, SFTPD, and KL-6 levels in BALF than did diseased controls. Patients with iPAP had significantly higher levels of IL-10, IL-8, CCL2, SFTPD, and KL-6 in blood than did lung controls and significantly higher levels of KL-6 in blood than did diseased controls. Levels of KL-6 both in BALF and blood were significantly correlated with serum lactate dehydrogenase level, arterial oxygen tension, and alveolar-arterial gradient in partial pressure of oxygen, the severity markers for iPAP, and were significantly higher in patients with iPAP who required subsequent therapeutic lung lavage. CONCLUSION: Patients with iPAP had elevated levels of SFTPD, KL-6, and cytokines in both BALF and blood. Elevated levels of KL-6 in both BALF and blood may be valuable in reflecting disease severity of patients with iPAP and in determining the need for therapeutic lung lavage.

Repeated thoracenteses affect proinflammatory cytokines, vascular endothelial growth factor, and fibrinolytic activity in pleural transudates.

BACKGROUND: Repeated thoracenteses is indicated in patients with refractory, symptomatic transudative effusions. However, their effect on cytokines and fibrinolytic activity in pleural transudates remains unclear. METHODS: Twenty-one patients with symptomatic, large amount of free-flowing transudative effusions caused by heart failure were studied. Thoracentesis with drainage of 500 mL of pleural fluid per day was done for 3 consecutive days (days 1 to 3). Pleural fluid characteristics, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-8, vascular endothelial growth factor (VEGF), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor type 1 (PAI-1) were measured during each tap. Chest ultrasonography was done on day 6 to detect the fibrin strands in pleural effusion and the outcome of effusion was evaluated within 7 days after repeated thoracenteses. RESULTS: Effusion levels of lactate dehydrogenase, neutrophils, TNF-alpha, IL-1 beta, IL-8, VEGF, and PAI-1 increased significantly during repeated thoracenteses. Furthermore, the values of PAI-1 and PAI-1/tPA obtained on days 2 and 3 were highly correlated with those of TNF-alpha, IL-1 beta, IL-8, and VEGF. On day 6, pleural fibrins were observed on chest ultrasonography in 6 patients (29%, fibrinous group) but were absent in the remaining 15 patients (nonfibrinous group). Compared with the nonfibrinous group, the effusion levels of TNF-alpha, IL-1 beta, VEGF, and PAI-1 on day 2 and day 3, and recurrence of symptomatic effusion after repeated thoracenteses were significantly higher in fibrinous group. CONCLUSIONS: Repeated thoracenteses may induce local release of proinflammatory cytokines, VEGF and PAI-1, which may result in fibrin deposition and impair resolution of pleural transudates.

Proinflammatory cytokines, transforming growth factor-beta1, and fibrinolytic enzymes in loculated and free-flowing pleural exudates.

STUDY OBJECTIVES: To measure tumor necrosis factor (TNF) alpha, interleukin (IL) 1beta, and transforming growth factor (TGF) beta1 in loculated and free-flowing pleural effusions caused by malignancy, tuberculosis (TB), and pneumonia and their relationship with plasminogen activator inhibitor-type 1 (PAI-1) and tissue-type plasminogen activator (tPA) and to compare the differences between loculated and free-flowing effusions. DESIGN: A prospective study. PATIENTS AND METHODS: The effusion levels of TNF-alpha, IL-1beta, TGF-beta1, PAI-1, and tPA were measured in 29 patients with malignant effusions, 19 patients with TB, and 30 patients with parapneumonic effusions. Pleural effusions were divided into loculated and free-flowing groups by imaging studies. A group of 42 patients with loculated effusions was subdivided into primary and secondary loculation groups by chest ultrasonography. RESULTS: The median levels of TNF-alpha (87.0 pg/mL), IL-1beta (13.8 pg/mL), TGF-beta1 (10,952.9 pg/mL), PAI-1 (111.2 ng/mL), and lactate dehydrogenase (LDH) [498 IU/dL] in the loculated group were significantly higher than those in the free-flowing group (TNF-alpha, 15.0 pg/mL; IL-1beta, 2.9 pg/mL; TGF-beta1, 6,117.3 pg/mL; PAI-1, 61.5 ng/mL, and LDH, 266 IU/dL). In both the loculated and free-flowing effusions, the levels of TGF-beta1 correlated positively with those of TNF-alpha (r = 0.51 and p < 0.001 vs r = 0.42 and p < 0.05, respectively) and IL-1beta (r = 0.52 and p < 0.001 vs r = 0.49 and p < 0.01, respectively), and the values of PAI-1 correlated positively with those of TNF-alpha (r = 0.59 and p < 0.001 vs r = 0.55 and p < 0.001, respectively), IL-1beta (r = 0.35 and p < 0.05 vs r = 0.47 and p < 0.01, respectively), and TGF-beta1 (r = 0.53 and p < 0.001 vs r = 0.58 and p < 0.001, respectively). In contrast, the levels of tPA correlated negatively with those of TNF-alpha (r = -0.37, p < 0.05) and IL-1beta (r =-0.56, p < 0.001) in loculated effusions. Twenty-seven of 42 patients with loculated effusions were classified into a secondary loculation group, which, compared with the primary loculation group, had significantly higher median levels of effusion TNF-alpha (119.2 vs 14.2 pg/mL, respectively; p = 0.001), IL-1beta (33.3 vs 3.4 pg/mL, respectively; p < 0.001), TGF-beta1 (13,152.7 vs 7746.0 pg/mL, respectively; p = 0.041), and PAI-1 (114.9 vs 94.1 pg/mL, respectively; p = 0.019). CONCLUSION: Compared with free-flowing effusions, fibrinolytic activity was depressed in loculated effusions. A higher intensity of pleural inflammation in loculated effusions may enhance the release of TNF-alpha, IL-1beta, and TGF-beta1, which may subsequently increase the levels of PAI-1. The imbalance of PAI-1 and tPA in pleural spaces may lead to fibrin deposition and loculation of pleural effusions.

Cytokines and fibrinolytic enzymes in tuberculous and parapneumonic effusions.

Tuberculous (TB) pleurisy and parapneumonic effusion (PPE) are common causes of pleural fibrosis. The mechanisms underlying fibrin deposition may be different since involved inflammatory cells are distinct. In this study, we measured various cytokines and fibrinolytic enzymes and compared the differences between the two effusions. PPE was further divided into noncomplicated PPE and complicated PPE/empyema subgroups. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8, macrophage inflammatory protein (MIP)-1beta, monocyte chemoattractant protein (MCP)-1, plasminogen activator inhibitor type 1 (PAI-1) and tissue type plasminogen activator (tPA) were measured using enzyme-linked immunosorbent assays. Significantly higher values of PAI-1, PAI-1/tPA ratio, IL-1beta, IL-8 and MIP-1beta and significantly lower values of TNF-alpha, IL-6 and MCP-1 were observed in PPE/empyema than in TB effusions. Compared to noncomplicated PPE, complicated PPE/empyema had significantly higher levels of TNF-alpha, IL-1beta, IL-8 and MIP-1beta. TB pleurisy patients who had higher effusion levels of TNF-alpha, IL-1beta and IL-8 were predisposing to residual pleural thickening. The underlying mechanisms of fibrin formation and deposition between the two effusions studied (PPE/empyema and TB pleurisy) could not be fully explained by the results of the present study. More studies are needed to explore this further.

Effect of body position on gas exchange in patients with idiopathic pulmonary alveolar proteinosis: no benefit of prone positioning.

BACKGROUND: Prone positioning may improve oxygenation in patients with acute lung injury/ARDS. However, the beneficial effect of prone positioning on gas exchange has never been investigated in patients with diffuse pulmonary infiltrates who breathe spontaneously. OBJECTIVE: To evaluate the effect of body position on gas exchange in patients with idiopathic pulmonary alveolar proteinosis (PAP) with special reference to the benefit of prone positioning. DESIGN: A prospective study. SETTING: Tertiary medical center. PATIENTS AND METHODS: Eight patients with PAP were studied on 25 occasions using spirometry, body plethysmography, and single-breath diffusing capacity of the lung for carbon monoxide (Dlco). Arterial blood gas levels were measured in the sitting position and in four lying positions randomly while patients breathed room air. To serve as control subjects, 16 age-matched healthy hospital personnel were studied. To evaluate the impact of oxygen therapy on positional effect in gas exchange, arterial blood gas levels were measured in the supine and prone positions in some PAP patients while breathing 40% oxygen. RESULTS: Normal to varying degrees of restrictive ventilatory defect and gas exchange impairment, as evidenced by Dlco, Pao(2), and alveolar-arterial oxygen pressure difference (P[A-a]O(2)), were found in PAP patients. The ventilatory function parameters correlated positively with Pao(2) and negatively with P(A-a)O(2). The values of Pao(2) and P(A-a)O(2) measured in four lying positions showed no significant difference in both PAP patients and healthy control subjects. Furthermore, the differences in Pao(2) and P(A-a)O(2) between measurements made in the supine and prone positions and the ratio of Pao(2) measured in the prone position/Pao(2) measured in the supine position were comparable between PAP patients and healthy control subjects. Arterial blood gas levels showed no significant difference between measurements made in PAP patients in the supine and prone positions while breathing 40% oxygen. CONCLUSIONS: Positional change did not significantly affect gas exchange, and no benefit of prone positioning was found in both PAP patients and healthy control subjects. Further studies are needed to verify the benefit of prone ventilation in patients with diffuse pulmonary disorders who breathe spontaneously.

Effect of repeated thoracenteses on fluid characteristics, cytokines, and fibrinolytic activity in malignant pleural effusion.

OBJECTIVE: To evaluate the effect of repeated thoracenteses on the fluid characteristics and the levels of various cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-5, IL-6, and IL-8, and of plasminogen activator inhibitor type 1 (PAI-1) and tissue type plasminogen activator in malignant pleural effusion and its clinical significance. DESIGN: A prospective study. PATIENTS AND METHODS: Twenty-six patients with symptomatic and a large amount of free-flow malignant pleural effusions were studied. Thoracentesis with drainage of 500 mL of pleural fluid per day was performed for 3 continuous days (days 1 to 3). The effusion samples were collected to evaluate the changes of fluid characteristics, cytokine levels, and fibrinolytic activity. Chest ultrasonography was done on day 6 to observe the presence of fibrin strands. The result of pleurodesis was evaluated in the patients classified into groups based on chest ultrasonographic findings. RESULTS: The values of TNF-alpha, PAI-1, IL-8, and neutrophil count in pleural fluid increased significantly during repeated thoracenteses in 26 patients studied. A positive correlation was found between the concentrations of TNF-alpha and PAI-1 and between the values of IL-8 and neutrophils. On day 6, fibrin strands were observed in the pleural effusion on chest ultrasonography in 11 patients (42%, fibrinous group) but were absent in the remaining 15 patients (nonfibrinous group). During repeated thoracenteses, a significant increase of effusion PAI-1 and TNF-alpha was observed in the fibrinous group but not in the nonfibrinous group. In addition, the levels of effusion PAI-1 and TNF-alpha obtained from day 2 and day 3 were significantly higher in the fibrinous group than in the nonfibrinous group. The success rate of pleurodesis was significantly higher in the fibrinous group (11 of 11 patients, 100%) than in the nonfibrinous group (8 of 12 patients, 67%). CONCLUSIONS: Repeated thoracenteses may cause pleural inflammation and induce local release of proinflammatory cytokine as TNF-alpha, which may subsequently enhance the release of PAI-1 and lead to fibrin formation in malignant effusion. The presence of fibrin strands after repeated thoracenteses may be of considerable value in predicting the success of subsequent pleurodesis in patients with malignant pleural effusions.