39024721
Efficacy and safety of iodopovidone in chemical pleurodesis: a meta-analysis of observational studies.
The search for an 'ideal' agent for pleurodesis continues. Iodopovidone is a topical antiseptic and has been shown to be safe and effective in many studies. The aim of this study was to evaluate the efficacy and safety of iodopovidone as an agent for chemical pleurodesis. We performed a systematic review of all the observational trials which have used iodopovidone for chemical pleurodesis. Six studies including 265 patients who had undergone chemical pleurodesis with iodopovidone were included for this analysis. Iodopovidone was used for variety of indications, which included pleural effusion (157 patients), and pneumothorax (108 patients). Pleurodesis was performed through tube thoracostomy in 144 patients and through thoracoscopy in 121 patients. The success rate of pleurodesis varied from 64.2% to 100%, and summary success rate of all the studies was 90.6% (95% confidence intervals [CI], 86.4-93.8). The success rate was independent for the procedure (tube thoracostomy [126/144; 87.5%, 95% CI 80.9-92.4] or thoracoscopy [114/121; 94.2%, 95% CI 88.4-97.6]) used for performing pleurodesis or for the indication (pleural effusion [139/157; 88.5%, 95% CI 82.5-93.1] or pneumothorax [101/108; 93.5%, 95% CI 87.1-97.4]). The only significant complication reported was chest pain of varying degree. Systemic hypotension was reported in three patients in only one study. There were no deaths related to chemical pleurodesis with iodopovidone. Overall, this review supports the safety and efficacy of iodopovidone as an agent for chemical pleurodesis in cases of recurrent pleural effusions and pneumothoraces regardless of their etiology.
26068481
Efficacy and safety of iodopovidone pleurodesis through tube thoracostomy.
OBJECTIVE
To evaluate the efficacy and safety of iodopovidone as an agent for pleurodesis through tube thoracostomy in patients with recurrent pleural effusions and pneumothorax.


METHODS
This was a prospective study in which pleurodesis was performed with a solution of 20 mL 10% iodopovidone and 80 mL normal saline solution infused through a tube thoracostomy and left in the pleural cavity for 4 h.


RESULTS
A total of 64 patients (34 men) with a mean (+/-SD) age of 47.1 +/- 15.4 years were included. There were 37 cases of pleural effusion and 27 of pneumothorax. A complete response (neither reaccumulation of fluid nor recurrence of pneumothorax) was obtained in 32 (86.5%) patients with pleural effusion and 25 (92.6%) patients with pneumothorax. A second procedure (i.e. repeated pleurodesis) was attempted successfully in four patients in the pleural effusion group. All patients experienced chest pain to a varying degree as recorded on a Visual Analogue Scale (median 50.5, range 10-95). Seven patients developed fever and one immunocompromised patient developed empyema following the procedure. There were no recurrences at a median follow up of 5 months (range 3-15 months) in the pleural effusion group, and 13 months (range 6-24 months) in the pneumothorax group.


CONCLUSIONS
Iodopovidone can be used as an effective and safe agent for (chemical) pleurodesis (through tube thoracostomy), which is inexpensive and readily available.
45424950
It is time to "SALVAGE" patients with severe sepsis.
33491888
Noninvasive ventilation in ARDS caused by Mycobacterium tuberculosis: report of three cases and review of literature
3038618
Is the mortality higher in the pulmonary vs the extrapulmonary ARDS? A meta analysis.
BACKGROUND AND AIM
ARDS can occur from the following two pathogenetic pathways: a direct pulmonary injury (ARDSp); and an indirect injury (ARDSexp). The predisposing clinical factor can influence the pathogenesis and clinical outcome of ARDS. This metaanalysis was aimed at evaluating whether there is any difference in mortality between the two groups.


METHODS
We searched the MEDLINE, EMBASE, and CINAHL databases for relevant studies published from 1987 to 2007, and included studies that have reported mortality in the two groups of ARDS. We calculated the odds ratio (OR) and 95% confidence interval (CI) to assess mortality in patients with ARDSp vs patients with ARDSexp and pooled the results using three different statistical models.


RESULTS
Our search yielded 34 studies. In all, the studies involved 4,311 patients with 2,330 patients in the ARDSp group and 1,981 patients in the ARDSexp group. The OR of mortality in ARDSp group compared to the ARDSexp group was 1.11 (95% CI, 0.88 to 1.39), as determined by the random-effects model; 1.04 (95% CI, 0.92 to 1.18), as determined by the fixed-effects model; and 1.04 (95% CI, 0.92 to 1.18), as determined by the exact method, indicating that mortality is similar in the two groups. The mortality was no different whether the studies were classified as prospective (OR, 1.15; 95% CI, 0.87 to 1.51) or retrospective (OR, 1.01; 95% CI, 0.61 to 1.69); small (OR, 1.11; 95% CI, 0.77 to 1.60) or large (OR, 1.1; 95% CI, 0.82 to 1.49); or observational (OR, 1.10; 95% CI, 0.82 to 1.49) or interventional (OR, 0.97; 95% CI, 0.79 to 1.19). There was methodological and statistical heterogeneity (I(2), 50.9%; 95% CI, 21.3 to 66.2%; chi(2) statistic, 67.22; p = 0.0004).


CONCLUSIONS
The results of this study suggest that there is no difference in mortality between these two groups. Further studies should focus on specific etiologies within the subgroups rather than focusing on the broader division of ARDSp and ARDSexp.
22528299
Pulmonary hypertension as a presenting manifestation of allergic bronchopulmonary aspergillosis.
The case of a 46-year-old lady who presented with respiratory failure and pulmonary hypertension in the absence of clinical signs of asthma or bronchiectasis, and in whom a diagnosis of allergic bronchopulmonary aspergilloma [ABPA] was made subsequently on the basis of radiological and laboratory investigations is reported. Symptomatic and objective improvement was seen with corticosteroid therapy. To the best of the authors' knowledge, such an occurrence has not been reported previously. This case highlights the importance of keeping a high index of suspicion while investigating a patient with pulmonary hypertension in whom the aetiology is not apparent on initial evaluation. Identification of the disease, in its early-stage, can prevent progression to bronchiectasis and fibrotic lung disease, and thus, patients can be saved from the morbidity related to end-stage disease.
39974976
Antiproteinuric effect of oral paricalcitol in chronic kidney disease.
BACKGROUND
Proteinuria is a marker of cardiovascular and renal disease in patients with chronic kidney disease (CKD), and reduction in proteinuria has been associated with improved cardiovascular and renal outcomes. While active vitamin D and its analogs have been shown to have renal protective effects in animals, these hormones have not been shown to reduce proteinuria in CKD patients.


METHODS
In three double-blind, randomized, placebo-controlled studies to evaluate the safety and efficacy of oral paricalcitol, 220 CKD stage 3 and 4 patients with secondary hyperparathyroidism (SHPT) were randomized to oral paricalcitol (N= 107, mean dose 9.5 microg/week) or placebo (N= 113) and followed for up to 24 weeks. In conjunction with other safety measures, proteinuria was measured by dipstick and read by an automated reader at the beginning and end of trial. We subsequently analyzed the dipstick data to evaluate the effect of paricalcitol on proteinuria.


RESULTS
At baseline, proteinuria was present in 57 patients randomized to oral paricalcitol and 61 patients randomized to placebo (NS). At the final visit, 29/57 (51%) of the paricalcitol patients compared to 15/61 (25%) placebo patients had reduction in proteinuria, P= 0.004 (odds for reduction in proteinuria 3.2 times greater for paricalcitol patients, 95% CI 1.5-6.9). For the patients who had both proteinuria at baseline and parathyroid hormone (PTH) suppression (end point defined as 2 consecutive > or =30% decreases in iPTH from baseline), 27/51 (53%) patients had a reduction in the proteinuria in the paricalcitol group and 0/7 (0%) had a reduction in proteinuria in the placebo group. Reduction of proteinuria favored patients on paricalcitol, regardless of age, sex, race, diabetes mellitus, hypertension, or use of therapies to block the renin-angiotensin-aldosterone system (RAAS).


CONCLUSION
Our results demonstrate that the reduction in proteinuria was associated with paricalcitol treatment, and the reduction in proteinuria was independent of concomitant use of agents that block the RAAS. Paricalcitol as a potential pharmacologic means of reducing proteinuria in CKD patients warrants further investigation.
30259650
Cell signaling and regulators of cell cycle as molecular targets for prostate cancer prevention by dietary agents.
Prostate cancer (PCA) is the most common invasive malignancy and leading cause (after lung) of cancer deaths in males. Since PCA is initially androgen-dependent, strategies are targeted toward androgen depletion for its control. However, tumor re-growth mostly occurs following this modality, and is androgen-independent. A loss of functional androgen receptor and an enhanced expression of growth factor receptors (e.g. erbB family members) and associated ligands have been shown to be the causal genetic events in PCA progression. These genetic alterations lead to an epigenetic mechanism where a feed-back autocrine loop between membrane receptor (e.g. epidermal growth factor receptor [erbB1] and associated ligand (e.g. transforming growth factor-alpha) results in an enhanced activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) as an essential component of the uncontrolled growth of PCA at an advanced and androgen-independent stage. Together, we rationalized that inhibiting these epigenetic events would be useful in controlling advanced PCA growth. Dietary polyphenolic flavonoids and isoflavones are being studied extensively as cancer-preventive and interventive agents. Therefore, we focused our attention on silymarin, genistein, and epigallocatechin 3-gallate (EGCG), present in milk thistle, soy beans, and green tea, respectively. The effect of these agents was assessed on the erbB1-Shc-ERK1/2 signal transduction pathway, cell cycle regulatory molecules, and cell growth and death. In androgen-independent human prostate carcinoma DU145 cells, silymarin, genistein, and EGCG resulted in a significant to complete inhibition of transforming growth factor-alpha-caused activation of membrane receptor erbB1 followed by inhibition of downstream cytoplasmic signaling target Shc activation and a decrease in its binding with erbB1, without an alteration in their protein expression. Silymarin and genistein also inhibited ERK1/2 activation, suggesting that these agents impair the activation of erbB1-Shc-ERK1/2 signaling in DU145 cells. In the case of EGCG, a further increase in ERK1/2 activation was observed that was related to its pro-oxidant and apoptotic activities. Silymarin, genistein, and EGCG also resulted in a significant induction of Cip1/p21 and Kip1/p27 and a decrease in cyclin-dependent kinase (CDK) 4, but a moderate inhibition of CDK2, cyclin D1, and cyclin E was observed. An enhanced level of Cip1/p21 and Kip1/27 also led to an increase in their binding to CDK4 and CDK2. Treatment of cells with silymarin, genistein, and EGCG also resulted in strong cell growth inhibition at lower doses, and complete inhibition at higher doses. In contrast to silymarin, higher doses of genistein also showed cell death. A more profound cytotoxic effect was observed in the case of EGCG, with strong cell death at lower doses and complete loss of viability at higher doses. Together, these results suggest that cell signaling and regulators of cell cycle are potential epigenetic molecular targets for prostate cancer prevention by dietary agents. More studies, therefore, are needed with these agents to explore their anticarcinogenic potential against human prostate cancer.
36066210
First-line therapy for ovarian cancer with carboplatin followed by paclitaxel-gemcitabine (SCOTROC5): a feasibility study and comparative analysis of the SCOTROC series.
BACKGROUND
We have conducted a series of four feasibility studies in stage Ic-IV ovarian cancer exploring six sequential first-line schedules with the same entry criteria in a total of 339 patients. Here we present the results of the sixth study, and an analysis of the overall series.


METHODS
In this trial patients received 4 cycles of carboplatin AUC 7 every 3 weeks, followed by 4 cycles of concurrent paclitaxel 175 mg/m(2) (day 1) and gemcitabine 1000 mg/m(2) (days 1 and 8) every 3 weeks. The primary end-point of the trial was feasibility of administering all cycles of planned chemotherapy to >60% of patients.


RESULTS
Fifty-four patients were recruited to the trial between June 05 and June 06. A total of 40 (74.1%) patients received all 8 cycles of treatment. Reasons for early discontinuation included toxicity (n=8) and disease progression (n=4). The overall response rate was 73.7%, and the median progression free survival (PFS) was 14.2 months with a median follow-up of 24 months. A comparative analysis of all six regimens from the SCOTROC series suggests that the sequential schedule in which paclitaxel was given weekly (median PFS 19.5m) is most effective.


CONCLUSION
The sequential schedule explored in this trial is feasible, but comparative efficacy analysis suggests that trials involving weekly paclitaxel should be prioritised for further study.
30954752
Salt, salt sensitivity, and the endothelium: a pathway to discovery of molecular mechanisms.
See related article, pp 951–956

This issue of Hypertension contains a report of molecular mechanisms transducing dietary salt intake1 that may have broad clinical relevance. These molecular mechanisms are complex, but to begin to understand this study we have to understand the importance of dietary salt intake and salt sensitivity. This background will be discussed in some detail before discussing the molecular mechanisms.

Although cohort studies have called into question the role of dietary salt intake in causing hypertension,2 cause and effect relationships are most convincing when demonstrated using randomized clinical trials. It would be unethical to perform a randomized clinical trial in which the dietary intake of salt (sodium chloride) is increased for years in humans to observe an increase in blood pressure. However, such an experiment in primates has been performed by Denton et al,3 who studied in Gabon, Africa, 26 chimpanzees. Chimpanzees have a native diet that is vegetarian and is very high in potassium content. The baseline sodium intake in these primates was only 6 mEq/d; in contrast, that of K was 235 mEq/d. Blood pressure was measured in the 26 animals for 1 year. Subsequently, among half the animals, increasing amounts of salt (in increments of 5 g/d sodium) were added to a diet to a steady-state level of 15 g/d. This dietary intake was maintained for 16 months. After this period of dietary supplementation, the diet was switched to baseline and observations made for another 6 months. A dose–response relationship between salt supplementation and blood pressure increment was seen. With 15 g/d sodium supplementation for 67 weeks, the change from baseline in blood pressure was 33/10 mm Hg. In comparison, 5 g/d sodium supplementation for 19 weeks provoked blood pressure change of 12/0 mm Hg. Notably, plasma renin activity was reduced with salt …
22856684
Prediction of hypertension in chronic hemodialysis patients.
BACKGROUND
There are no universally accepted criteria for the diagnosis of hypertension in hemodialysis (HD) patients. We sought to determine the clinical performance of predialysis and postdialysis systolic and diastolic blood pressure values (BPs) in diagnosing hypertension or assessing its control.


METHODS
Seventy patients [77% African American, 46% females, mean age 59 +/- 17 (SD) years, 34% diabetics] on chronic HD underwent a single 44-hour interdialytic ambulatory blood pressure monitoring (ABPM) and concomitant recording of BP by conventional syphygmomanometer in the HD unit for two weeks. Hypertension was defined as systolic BP (SBP) > or =135 mm Hg or diastolic BP (DBP) > or =85 mm Hg on an average 44-hour ABPM.


RESULTS
Average ABP was 144 +/- 22/81 +/- 11 mm Hg. Seventy-three percent of the patients had systolic hypertension; 40% had diastolic hypertension, and 24% were normotensive or had well-controlled BP. Area under the curve of receiver operating characteristic (ROC) curves exceeded 80% for all BPs, but the thresholds for best sensitivity and specificity were markedly different for predialysis and postdialysis BPs. A two-week averaged predialysis BP of > 150/85 mm Hg or a postdialysis BP of > 130/75 mm Hg had at least 80% sensitivity in diagnosing hypertension. Specificity of at least 80% was achieved if predialysis BP of > 160/90 mm Hg or postdialysis BP of > 140/80 mm Hg was used. There was poor agreement between HD unit BP and ABP values.


CONCLUSIONS
HD unit BP values can be used to identify the presence or absence of hypertension, although prediction of ambulatory BPs from HD unit BP values cannot be made reliably in individual patients.