Ability of Procalcitonin to Discriminate Infection from Non-Infective Inflammation Using Two Pleural Disease Settings

Procalcitonin has been shown to be useful in separating infection from non-infective disorders. However, infection is often paralleled by tissue inflammation. Most studies supporting the use of procalcitonin were confounded by more significant inflammation in the infection group. Few studies have examined the usefulness of procalcitonin when adjusted for inflammation.Pleural inflammation underlies the development of most exudative effusions including pleural infection and malignancy. Pleurodesis, often used to treat effusions, involves provocation of intense aseptic pleural inflammation. We conducted a two-part proof-of-concept study to test the specificity of procalcitonin in differentiating infection using cohorts of patients with pleural effusions of infective and non-infective etiologies, as well as subjects undergoing pleurodesis.

Methods

We measured the blood procalcitonin level (i) in 248 patients with pleural infection or with non-infective pleural inflammation, matched for severity of systemic inflammation by C-reactive protein (CRP), age and gender; and (ii) in patients before and 24–48 hours after induction of non-infective pleural inflammation (from talc pleurodesis).

Results

1) Procalcitonin was significantly higher in patients with pleural infection compared with controls with non-infective effusions (n = 32 each group) that were case-matched for systemic inflammation as measured by CRP [median (25–75%IQR): 0.58 (0.35–1.50) vs 0.34 (0.31–0.42) µg/L respectively, p = 0.003]. 2) Talc pleurodesis provoked intense systemic inflammation, and raised serum CRP by 360% over baseline. However procalcitonin remained relatively unaffected (21% rise). 3) Procalcitonin and CRP levels did not correlate. In 214 patients with pleural infection, procalcitonin levels did not predict the survival or need for surgical intervention.

Conclusion

Using a pleural model, this proof-of-principle study confirmed that procalcitonin is a biomarker specific for infection and is not affected by non-infective inflammation. Procalcitonin is superior to CRP in distinguishing infection from non-infective pleural diseases, even when controlled for the level of systemic inflammation.     

Clinical Importance of Angiogenic Cytokines,Fibrinolytic Activity and Effusion Size in Parapneumonic Effusions

Objective

To investigate the relationship among angiogenic cytokines, fibrinolytic activity and effusion size in parapneumonic effusion (PPE) and their clinical importance.

Methods

From January 2008 through December 2010, 26 uncomplicated (UPPE) and 38 complicated (CPPE) PPE were studied. Based on chest ultrasonography, there were non-loculated in 30, uni-loculated in 12, and multi-loculated effusions in 22 patients. The effusion size radiological scores, and effusion vascular endothelial growth factor (VEGF), interleukin (IL)-8, plasminogen activator inhibitor type-1 (PAI-1) and tissue type plasminogen activator (tPA) were measured on admission. Treatment outcome and pleural fibrosis, defined as radiological residual pleural thickening (RPT), were assessed at 6-month follow-up.

Results

The effusion size and effusion VEGF, IL-8 and PAI-1/tPA ratio were significantly higher in CPPE than in UPPE, and significantly higher in multi-loculated PPE than in non-locualted and uni-loculated PPE, respectively. VEGF (cutoff value 1975 pg/ml) and IL-8 (cutoff value 1937 pg/ml) seemed best to discriminate between UPPE and CPPE. VEGF, IL-8 and effusion size correlated positively with PAI-1/tPA ratio in both UPPE and CPPE. Moreover, the level of VEGF, but not IL-8, correlated positively with effusion size in all patients (r = 0.79, p<0.001) and in UPPE (r = 0.64, p<0.001) and CPPE (r = 0.71, p<0.001) groups. The patients with higher VEGF or greater effusion were prone to have medical treatment failure (n = 10; VEGF, odds ratio 1.01, p = 0.02; effusion size, odds ratio 1.26, p = 0.01). Additionally, ten patients with RPT had larger effusion size and higher levels of VEGF and PAI-1/tPA ratio than did those without.

Conclusions

In PPE, VEGF and IL-8 levels are valuable to identify CPPE, and higher VEGF level or larger effusion is associated with decreased fibrinolytic activity, development of pleural loculation and fibrosis, and higher risk of medical treatment failure.     

Dynamic and Volumetric Variables Reliably Predict Fluid Responsiveness in a Porcine Model with Pleural Effusion

Background

The ability of stroke volume variation (SVV), pulse pressure variation (PPV) and global end-diastolic volume (GEDV) for prediction of fluid responsiveness in presence of pleural effusion is unknown. The aim of the present study was to challenge the ability of SVV, PPV and GEDV to predict fluid responsiveness in a porcine model with pleural effusions.

Methods

Pigs were studied at baseline and after fluid loading with 8 ml kg⁻¹ 6% hydroxyethyl starch. After withdrawal of 8 ml kg⁻¹ blood and induction of pleural effusion up to 50 ml kg⁻¹ on either side, measurements at baseline and after fluid loading were repeated. Cardiac output, stroke volume, central venous pressure (CVP) and pulmonary occlusion pressure (PAOP) were obtained by pulmonary thermodilution, whereas GEDV was determined by transpulmonary thermodilution. SVV and PPV were monitored continuously by pulse contour analysis.

Results

Pleural effusion was associated with significant changes in lung compliance, peak airway pressure and stroke volume in both responders and non-responders. At baseline, SVV, PPV and GEDV reliably predicted fluid responsiveness (area under the curve 0.85 (p<0.001), 0.88 (p<0.001), 0.77 (p = 0.007). After induction of pleural effusion the ability of SVV, PPV and GEDV to predict fluid responsiveness was well preserved and also PAOP was predictive. Threshold values for SVV and PPV increased in presence of pleural effusion.

Conclusions

In this porcine model, bilateral pleural effusion did not affect the ability of SVV, PPV and GEDV to predict fluid responsiveness.     

Assessment of the N-PCR Assay in Diagnosis of Pleural Tuberculosis: Detection of M.tuberculosis in Pleural Fluid and Sputum Collected in Tandem

Background

The nonspecific clinical presentation and paucibacillary nature of tuberculous pleuritis remains a challenge for diagnosis. Diagnosis of tuberculous pleural effusion depends on the demonstration of the presence of tubercle bacilli in the sputum, pleural fluid, or pleural biopsy specimen, or demonstration of granuloma in pleura by histological examination. We examined the clinical utility of the diagnosis of pleural tuberculosis using the in house N-PCR assay, AFB smear microscopy and culture. Besides pleural fluid the inclusion of sputum in the efficacy of diagnosis of pleural tuberculosis was scrutinized.

Methodology/Principal Findings

Pleural fluid and sputum samples of 58 tuberculous and 42 non-tuberculous pleural effusion patients were processed for AFB smear microscopy, culture and the N-PCR assay. Mycobacteria were detected exclusively in tuberculous pleural effusion samples. None of the non-tuberculous pleural effusion samples were positive for mycobacteria. Comparative analysis showed that the N-PCR assay had the highest sensitivity. Inclusion of sputum along with pleural fluid increased N-PCR sensitivity from 51.7 to 70.6% (p<0.0001).This improved sensitivity was reflected in AFB smear microscopy and isolation by culture. The sensitivity enhanced on inclusion of sputum from 3.4 (p = 0.50) to 10.3% (p = 0.038) for AFB smear microscopy and for isolation of mycobacteria from 10.3(p = 0.03) to 22.4% (p = 0.0005). Thirteen isolates were obtained from 58 pleural tuberculosis patients. Eleven mycobacterial isolates were identified as M.tuberculosis and two as M.fortuitum and M.chelonae. Complete concordance was seen between the biochemical identification of isolates and the N-PCR identification of mycobacterial species prior to isolation.

Conclusions/Significance

To the best of our knowledge this is the first PCR based report on utility of sputum for diagnosis of pleural tuberculosis. The present study demonstrates that a combination of pleural fluid with sputum sample and N-PCR improved the diagnosis of pleural tuberculosis.     

CD39+ Regulatory T cells suppress generation and differentiation of Th17 cells in human malignant pleural effusion via a LAP-dependent mechanism

Background

Both regulatory T cells (Tregs) and T helper IL-17-producing cells (Th17 cells) have been found to be involved in human malignancies, however, the possible implication of Tregs in regulating generation and differentiation of Th17 cells in malignant pleural effusion remains to be elucidated.

Methods

The numbers of both CD39⁺Tregs and Th17 cells in malignant pleural effusion and peripheral blood from patients with lung cancer were determined by flow cytometry. The regulation and mechanism of Tregs on generation and differentiation of Th17 cells were explored.

Results

Both CD39⁺Tregs and Th17 cells were increased in malignant pleural effusion when compared with blood, and the numbers of CD39⁺Tregs were correlated negatively with those of Th17 cells. It was also noted that high levels of IL-1β, IL-6, and TGF-β1 could be observed in malignant pleural effusion when compared the corresponding serum, and that pleural CD39⁺Tregs could express latency-associated peptide on their surface. When naïve CD4⁺ T cells were cocultured with CD39⁺Tregs, Th17 cell numbers decreased as CD39⁺Treg numbers increased, addition of the anti-latency-associated peptide mAb to the coculture reverted the inhibitory effect exerted by CD39⁺Tregs.

Conclusions

Therefore, the above results indicate that CD39⁺Tregs inhibit generation and differentiation of Th17 cells via a latency-associated peptide-dependent mechanism.     

信息管理系统下胸腔镜胸膜固定术治疗恶性胸腔积液

目的:分析基于信息管理系统的胸腔镜滑石粉胸膜固定术控制恶性胸腔积液患者术后的并发症,死亡率及生存时间。方法:2011年9月至2014年10月,一共400个患者完成了胸腔镜辅下滑石粉胸膜固定术。对手术前后的患者的并发症,死亡率,成功率和中位生存时间进行评价。结果:中位随访时间为40个月(范围4-61月)。所有患者的呼吸困难症状都得到明显缓解。围手术期死亡率为0。患者对这一手术的耐受性良好,没有观察到明显的副作用。院内死亡率为2%,胸膜固定的成功率为85%。较差的KS评分及胸腔积液诊断到完成胸膜固定术之间的时间延误与院内死亡的发生明显相关。乳腺癌的生存情况最好,其次为卵巢癌,淋巴瘤和胸膜间皮瘤。结论:胸腔镜滑石粉胸膜固定术是一项安全有效的操作,胸膜固定的成功率较高,呼吸困难会能够得到长期有效的控制。     

Radiotherapy applications of patients with malignant mesothelioma: A single center experience

Background

In the management of malignant pleural mesothelioma, radiotherapy has been used for the purpose of prophylaxis to reduce the incidence of recurrence at surgical insertion sites or palliate the symptoms.

Aim

The purpose of the study was to evaluate the techniques and effectiveness of radiotherapy in malignant pleural mesothelioma.

Materials and methods

Forty-four (18 female, 26 male) patients diagnosed with malignant pleural mesothelioma were retrospectively evaluated. All patients had surgery or thoracoscopic biopsy for diagnosis, staging or treatment and all received palliative or prophylactic radiotherapy. Fifty-seven percent of the patients received chemotherapy.

Results

Prophylactic radiation was applied to 27 patients with 4–15 MeV electron energies. The median radiotherapy dose was 30 Gy with 3 Gy daily fraction dose. During treatment, 12 patients had grade 1 erythema according to the RTOG scale. In 3 (12%) patients, a local failure at treatment field was observed. Palliative radiotherapy was applied to 17 patients for pain palliation. The median radiation dose was 40 Gy with 2 Gy daily fraction dose by using 6–18 MV photon and/or 4–12 MeV electron energies. Two patients had grade 1 erythema and one patient had grade 2 odynophagy according to the RTOG scale. For 10 (59%) patients, palliation of chest pain was delivered. No late toxicity was observed for all cases.

Conclusion

Our experience showed that prophylactic and palliative radiotherapy are effective and safe therapy modalities in malignant pleural mesothelioma in preventing seeding metastasis at intervention sites or relieving pain. Prospective randomized studies are still needed to determine the benefits of radiotherapy application and to indicate optimum dose schemes.     

Iterative Thoracentesis as First-Line Treatment of Complicated Parapneumonic Effusion

Rationale

Optimal management of complicated parapneumonic effusions (CPPE) remains controversial.

Objectives

to assess safety and efficacy of iterative therapeutic thoracentesis (ITTC), the first-line treatment of CPPE in Rennes University Hospital.

Methods

Patients with CPPE were identified through our computerized database. We retrospectively studied all cases of CPPE initially managed with ITTC in our institution between 2001 and 2010. ITTC failure was defined by the need for additional treatment (i.e. surgery or percutaneous drainage), or death.

Results

Seventy-nine consecutive patients were included. The success rate was 81% (n = 64). Only 3 patients (4%) were referred to thoracic surgery. The one-year survival rate was 88%. On multivariate analysis, microorganisms observed in pleural fluid after Gram staining and first thoracentesis volume ≥450 mL were associated with ITTC failure with adjusted odds-ratios of 7.65 [95% CI, 1.44–40.67] and 6.97 [95% CI, 1.86–26.07], respectively. The main complications of ITTC were iatrogenic pneumothorax (n = 5, 6%) and vasovagal reactions (n = 3, 4%). None of the pneumothoraces required chest tube drainage, and no hemothorax or re-expansion pulmonary edema was observed.

Conclusions

Although not indicated in international recommendations, ITTC is safe and effective as first-line treatment of CPPE, with limited invasiveness.     

High Dose Rate versus Low Dose Rate Brachytherapy for Oral Cancer – A Meta-Analysis of Clinical Trials

Objective

To compare the efficacy and safety of high dose rate (HDR) and low dose rate (LDR) brachytherapy in treating early-stage oral cancer.

Data Sources

A systematic search of MEDLINE, EMBASE and Cochrane Library databases, restricted to English language up to June 1, 2012, was performed to identify potentially relevant studies.

Study Selection

Only randomized controlled trials (RCT) and controlled trials that compared HDR to LDR brachytherapy in treatment of early-stage oral cancer (stages I, II and III) were of interest.

Data Extraction and Synthesis

Two investigators independently extracted data from retrieved studies and controversies were solved by discussion. Meta-analysis was performed using RevMan 5.1. One RCT and five controlled trials (607 patients: 447 for LDR and 160 for HDR) met the inclusion criteria. The odds ratio showed no statistically significant difference between LDR group and HDR group in terms of local recurrence (OR = 1.12, CI 95% 0.62–2.01), overall mortality (OR = 1.01, CI 95% 0.61–1.66) and Grade 3/4 complications (OR = 0.86, CI 95% 0.52–1.42).

Conclusions

This meta-analysis indicated that HDR brachytherapy was a comparable alternative to LDR brachytherapy in treatment of oral cancer. HDR brachytherapy might become a routine choice for early-stage oral cancer in the future.     

The Effect of Pleural Abrasion on the Treatment of Primary Spontaneous Pneumothorax: A Systematic Review of Randomized Controlled Trials

Background

Pleural abrasion has been widely used to control the recurrence of primary spontaneous pneumothorax (PSP). However, controversy still exists regarding the advantages and disadvantages of pleural abrasion compared with other interventions in preventing the recurrence of PSP.

Methods

The PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched up to December 15, 2014 to identify randomized controlled trials (RCTs) that compared the effects of pleural abrasion with those of other interventions in the treatment of PSP. The study outcomes included the PSP recurrence rate and the occurrence rate of adverse effects.

Results

Mechanical pleural abrasion and apical pleurectomy after thoracoscopic stapled bullectomy exhibited similarly persistent postoperative air leak occurrence rates (p = 0.978) and 1-year PSP recurrence rates (p = 0.821), whereas pleural abrasion led to reduced residual chest pain and discomfort (p = 0.001) and a smaller rate of hemothorax (p = 0.036) than did apical pleurectomy. However, the addition of minocycline pleurodesis to pleural abrasion did not reduce the pneumothorax recurrence rate compared with apical pleurectomy (3.8% for both procedures) but was associated with fewer complications. There was no statistical difference in the pneumothorax recurrence rate between mechanical pleural abrasion and chemical pleurodesis with minocycline on either an intention-to-treat basis (4 of 42 versus 0 of 42, p = 0.12; Fisher exact test) or after exclusions (2 of 40 versus 0 of 42, p = 0.24; Fisher exact test). Pleural abrasion plus minocycline pleurodesis also did not reduce the pneumothorax recurrence rate compared with pleural abrasion alone (p = 0.055). Moreover, pleural abrasion plus minocycline pleurodesis was associated with more intense acute chest pain. The postoperative overall recurrence rate in patients who underwent staple line coverage with absorbable cellulose mesh and fibrin glue was similar to that with mechanical abrasion after thoracoscopic bullectomy (13.8% vs. 14.2%, respectively; p = 0.555), but staple line coverage resulted in less postoperative residual pain than mechanical abrasion (0.4% vs.3.2%; p<0.0001). Pleural abrasion after thoracoscopic wedge resection did not decrease the recurrence of pneumothorax compared with wedge resection alone (p = 0.791), but the intraoperative bleeding and postoperative pleural drainage rates were higher when pleural abrasion was performed.

Conclusions

In addition to resulting in the same pneumothorax recurrence rate, thoracoscopic pleural abrasion with or without minocycline pleurodesis is safer than apical pleurectomy in the treatment of PSP. However, minocycline pleurodesis with or without pleural abrasion is not any more effective than pleural abrasion alone. Moreover, additional mechanical abrasion is not safer than additional staple line coverage with absorbable cellulose mesh and fibrin glue after thoracoscopic bullectomy because of increased postoperative pain. Additionally, pleural abrasion after thoracoscopic wedge resection should not be recommended for routine application due to the greater incidence of adverse effects than wedge resection alone. However, further large-scale, well-designed RCTs are needed to confirm the best procedure.     

Occupational Complexity and Risk of Parkinson's Disease

Background

The etiology of Parkinson''s disease (PD) remains unclear, and environmental risk-factors such as occupation have attracted interest.

Objective

The goal was to investigate occupational complexity in relation to PD.

Methods

We conducted a population-based cohort study based on the Swedish Twin Registry that included 28,778 twins born between 1886 and 1950. We identified 433 PD cases during the study period. Data on occupation were collected from either the 1970 or 1980 Swedish census, and occupational complexity was assessed via a job exposure matrix. Cox proportional hazard regression analyses with age as the underlying time scale were used to assess PD risk as a function of the three domains of occupational complexity: data, people, and things. Sex and smoking were included as covariates. Analyses stratified by twin pair were conducted to test for confounding by familial factors.

Results

High occupational complexity with data and people was associated with increased risk overall (Hazard Ratio [HR] = 1.07, 95% confidence interval [CI] 1.02–1.14, and HR = 1.10, 95% CI 1.01–1.21, respectively), and in men (HR = 1.08, 95% CI 1.01–1.16, and HR = 1.15, 95% CI 1.03–1.28, respectively). Complexity with things was not associated with risk of PD. When the analyses were stratified by twin pair, the HRs for occupational complexity with data and people were attenuated in men.

Conclusions

High complexity of work with data and people is related to increased risk of PD, particularly in men. The attenuation of risk observed in the twin pair-stratified analyses suggests that the association may partly be explained by familial factors, such as inherited traits contributing to occupational selection or other factors shared by twins.     

Consuming More of Daily Caloric Intake at Dinner Predisposes to Obesity. A 6-Year Population-Based Prospective Cohort Study

Background/Objectives

It has been hypothesized that assuming most of the caloric intake later in the day leads to metabolic disadvantages, but few studies are available on this topic. Aim of our study was to prospectively examine whether eating more of the daily caloric intake at dinner leads to an increased risk of obesity, hyperglycemia, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD).

Subjects/Methods

1245 non-obese, non-diabetic middle-aged adults from a population-based cohort underwent a 3-day food record questionnaire at enrollment. Anthropometric values, blood pressure, blood metabolic variables, and estimated liver fat were measured at baseline and at 6-year follow-up.

Design

Prospective cohort study.

Results

Subjects were divided according to tertiles of percent daily caloric intake at dinner. A significant increase in the incidence rate of obesity (from 4.7 to 11.4%), metabolic syndrome (from 11.1 to 16.1%), and estimated NAFLD (from 16.5 to 23.8%) was observed from the lower to higher tertile. In a multiple logistic regression model adjusted for multiple covariates, subjects in the highest tertile showed an increased risk of developing obesity (OR = 2.33; 95% CI 1.17–4.65; p = 0.02), metabolic syndrome (OR = 1.52; 95% CI 1.01–2.30; p = 0.04), and NAFLD (OR = 1.56; 95% CI 1.10–2.22; p = 0.01).

Conclusions

Consuming more of the daily energy intake at dinner is associated with an increased risk of obesity, metabolic syndrome, and NAFLD.     

Factors Associated with Appointment Non-Adherence among African-Americans with Severe,Poorly Controlled Hypertension

Background

Missed appointments are associated with an increased risk of hospitalization and mortality. Despite its widespread prevalence, little data exists regarding factors related to appointment non-adherence among hypertensive African-Americans.

Objective

To investigate factors associated with appointment non-adherence among African-Americans with severe, poorly controlled hypertension.

Design and Participants

A cross-sectional survey of 185 African-Americans admitted to an urban medical center in Maryland, with severe, poorly controlled hypertension from 1999–2004. Categorical and continuous variables were compared using chi-square and t-tests. Adjusted multivariable logistic regression was used to assess correlates of appointment non-adherence.

Main Outcome Measures

Appointment non-adherence was the primary outcome and was defined as patient-report of missing greater than 3 appointments out of 10 during their lifetime.

Results

Twenty percent of participants (n = 37) reported missing more than 30% of their appointments. Patient characteristics independently associated with a higher odds of appointment non-adherence included not finishing high school (Odds ratio [OR] = 3.23 95% confidence interval [CI] (1.33–7.69), hypertension knowledge ([OR] = 1.20 95% CI: 1.01–1.42), lack of insurance ([OR] = 6.02 95% CI: 1.83–19.88), insurance with no medication coverage ([OR] = 5.08 95% CI: 1.05–24.63), cost of discharge medications ([OR] = 1.20 95% CI: 1.01–1.42), belief that anti-hypertensive medications do not work ([OR] = 3.67 95% CI: 1.16–11.7), experience of side effects ([OR] = 3.63 95% CI: 1.24–10.62), medication non-adherence ([OR] = 11.31 95% CI: 3.87–33.10). Substance abuse was not associated with appointment non-adherence ([OR] = 1.05 95% CI: 0.43–2.57).

Conclusions

Appointment non-adherence among African-Americans with poorly controlled hypertension was associated with many markers of inadequate access to healthcare, knowledge, attitudes and beliefs.     

Cranialization of the Frontal Sinus for Secondary Mucocele Prevention following Open Surgery for Benign Frontal Lesions

Objective

To compare frontal sinus cranialization to obliteration for future prevention of secondary mucocele formation following open surgery for benign lesions of the frontal sinus.

Study Design

Retrospective case series.

Setting

Tertiary academic medical center.

Patients

Sixty-nine patients operated for benign frontal sinus pathology between 1994 and 2011.

Interventions

Open excision of benign frontal sinus pathology followed by either frontal obliteration (n = 41, 59%) or frontal cranialization (n = 28, 41%).

Main Outcome Measures

The prevalence of post-surgical complications and secondary mucocele formation were compiled.

Results

Pathologies included osteoma (n = 34, 49%), mucocele (n = 27, 39%), fibrous dysplasia (n = 6, 9%), and encephalocele (n = 2, 3%). Complications included skin infections (n = 6), postoperative cutaneous fistula (n = 1), telecanthus (n = 4), diplopia (n = 3), nasal deformity (n = 2) and epiphora (n = 1). None of the patients suffered from postoperative CSF leak, meningitis or pneumocephalus. Six patients, all of whom had previously undergone frontal sinus obliteration, required revision surgery due to secondary mucocele formation. Statistical analysis using non-inferiority test reveal that cranialization of the frontal sinus is non-inferior to obliteration for preventing secondary mucocele formation (P<0.0001).

Conclusion

Cranialization of the frontal sinus appears to be a good option for prevention of secondary mucocele development after open excision of benign frontal sinus lesions.     

MRI Findings of Otic and Sinus Barotrauma in Patients with Carbon Monoxide Poisoning during Hyperbaric Oxygen Therapy

Background and Purpose

To study the MRI findings of otic and sinus barotrauma in patients with carbon monoxide(CO) poisoning during hyperbaric oxygen (HBO) therapy and examine the discrepancies of otic and sinus abnormalities on MRI between barotrauma and acute otitis media with effusion.

Materials and Methods

Eighty patients with CO-poisoning diagnosed with otic and sinus barotrauma after HBO therapy were recruited. Brain MRI was performed to predict delayed encephalopathy. Over the same period, 88 patients with acute otitis media with effusion on MRI served as control. The abnormalities of the middle ear and paranasal sinuses on MRI were noted and were compared between groups. Nine patients with barotrauma were followed up by MRI.

Results

In the barotrauma group, 92.5% of patients had bilateral middle ear abnormalities on MRI, and 60% of patients had both middle ear cavity and mastoid cavity abnormalities on MRI in both ears. Both rates were higher than those in the control group (p = 0.000). In the two groups, most abnormalities on MRI were observed in the mastoid cavity. The rate of sinus abnormalities of barotrauma was 66.3%, which was higher than the 50% in the control group (p = 0.033). In the nine patients with barotrauma followed up by MRI, the otic barotrauma and sinus abnormalities had worsened in 2 patients and 5 patients, respectively.

Conclusion

MRI is able to depict the abnormalities of otic and sinus barotrauma in patients with CO-poisoning during HBO therapy and to differentiate these from acute otitis media with effusion.     

Dacarbazine Combined Targeted Therapy versus Dacarbazine Alone in Patients with Malignant Melanoma: A Meta-Analysis

Background

Malignant melanoma is the most aggressive and deadly form of skin cancer. Dacarbazine (DTIC) has been the approved first-line treatment for metastatic melanoma in routine clinical practice. However, response rates with single-agent DTIC are low. The objective of this study was to compare the efficacy and safety of DTIC with or without placebo and DTIC-based combination therapies in patients with advanced metastatic melanoma.

Methods

We searched from electronic databases such as The Cochrane Library, MEDLINE, EBSCO, EMBASE, Ovid, CNKI, and CBMDisc from 2003 to 2013. The primary outcome measures were overall response and 1-year survival, and the secondary outcome measurements were adverse events.

Results

Nine randomized controlled trials (RCTs) involving 2,481 patients were included in the meta-analysis. DTIC-based combination therapies was superior to DTIC alone in overall response (combined risk ratio [RR]  = 1.60, 95% confidence interval [CI]: 1.27–2.01) and 1-year survival (combined RR = 1.26, 95% CI: 1.14–1.39). Patients with DTIC-based combination therapies had higher incidence of adverse events including nausea (combined RR = 1.23, 95% CI: 1.10–1.36), vomiting (combined RR = 1.73, 95% CI: 1.41–2.12) and neutropenia (combined RR = 1.75, 95% CI: 1.42–2.16) compared to the group for DTIC alone.

Conclusion

These data suggested that DTIC-based combination therapies could moderately improve the overall response and the 1-year survival but increased the incidence of adverse events. Further large-scale, high-quality, placebo-controlled, double-blind trials are needed to confirm this conclusion.     

Sleep Extension Improves Neurocognitive Functions in Chronically Sleep-Deprived Obese Individuals

Background

Sleep deprivation and obesity, are associated with neurocognitive impairments. Effects of sleep deprivation and obesity on cognition are unknown, and the cognitive long-term effects of improvement of sleep have not been prospectively assessed in short sleeping, obese individuals.

Objective

To characterize neurocognitive functions and assess its reversibility.

Design

Prospective cohort study.

Setting

Tertiary Referral Research Clinical Center.

Patients

A cohort of 121 short-sleeping (<6.5 h/night) obese (BMI 30–55 kg/m²) men and pre-menopausal women.

Intervention

Sleep extension (468±88 days) with life-style modifications.

Measurements

Neurocognitive functions, sleep quality and sleep duration.

Results

At baseline, 44% of the individuals had an impaired global deficit score (t-score 0–39). Impaired global deficit score was associated with worse subjective sleep quality (p = 0.02), and lower urinary dopamine levels (p = 0.001). Memory was impaired in 33%; attention in 35%; motor skills in 42%; and executive function in 51% of individuals. At the final evaluation (N = 74), subjective sleep quality improved by 24% (p<0.001), self-reported sleep duration increased by 11% by questionnaires (p<0.001) and by 4% by diaries (p = 0.04), and daytime sleepiness tended to improve (p = 0.10). Global cognitive function and attention improved by 7% and 10%, respectively (both p = 0.001), and memory and executive functions tended to improve (p = 0.07 and p = 0.06). Serum cortisol increased by 17% (p = 0.02). In a multivariate mixed model, subjective sleep quality and sleep efficiency, urinary free cortisol and dopamine and plasma total ghrelin accounted for 1/5 of the variability in global cognitive function.

Limitations

Drop-out rate.

Conclusions

Chronically sleep-deprived obese individuals exhibit substantial neurocognitive deficits that are partially reversible upon improvement of sleep in a non-pharmacological way. These findings have clinical implications for large segments of the US population.

Trail registration

www.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00261898","term_id":"NCT00261898"}}NCT00261898. NIDDK protocol 06-DK-0036     

Association between MLH1 -93G>A Polymorphism and Risk of Colorectal Cancer

Background

The -93G>A (rs1800734) polymorphism located in the promoter of mismatch repair gene, MLH1, has been identified as a low-penetrance variant for cancer risk. Many published studies have evaluated the association between the MLH1 -93G>A polymorphism and colorectal cancer (CRC) risk. However, the results remain conflicting rather than conclusive.

Objective

The aim of this study was to assess the association between the MLH1 -93G>A polymorphism and the risk of CRC.

Methods

To derive a more precise estimation of the association, a meta-analysis of six studies (17,791 cases and 13,782 controls) was performed. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the association. Four of these published studies were performed on subjects of known microsatellite instability (MSI) status. An additional analysis including 742 cases and 10,895 controls was used to assess the association between the MLH1 -93G>A polymorphism and the risk of MSI-CRC.

Results

The overall results indicated that the variant genotypes were associated with a significantly increased risk of CRC (AG versus GG: OR = 1.06, 95% CI = 1.01–1.11; AA/AG versus GG: OR = 1.06, 95% CI = 1.01–1.11). This increased risk was also found during stratified analysis of MSI status (AA versus GG: OR = 2.52, 95% CI = 1.94–3.28; AG versus GG: OR = 1.29, 95% CI = 1.10–1.52; AA/AG versus GG: OR = 1.45, 95% CI = 1.24–1.68; AA versus AG/GG: OR = 2.29, 95% CI = 1.78–2.96). Egger’s test did not show any evidence of publication bias.

Conclusion

Our results suggest that the MLH1 -93G>A polymorphism may contribute to individual susceptibility to CRC and act as a risk factor for MSI-CRC.     

Fasting Whole Blood Fatty Acid Profile and Risk of Type 2 Diabetes in Adults: A Nested Case Control Study

Objective

to determine the association of fasting whole blood fatty acid concentrations with incidence of type 2 diabetes in adults.

Methods

A nested case-control study of 187 subjects from a cohort of men and women aged 55–85 years from the Hunter Region, New South Wales, Australia. Fasting whole blood fatty acids were measured using gas chromatography and incidence of type 2 diabetes was ascertained by self-reported questionnaire at the study follow-up.

Results

After adjustment for potential confounding variables, positive associations with type 2 diabetes were seen for dihomo-gamma-linolenic acid (DGLA) (OR = 1.04, 95% CI:1.01–1.07, P = 0.01); arachidonic acid (ARA) (OR = 1.01, 95% CI:1.00–1.01, P = 0.002); alpha-linolenic acid (ALA) (OR = 1.10, 95% CI: 1.03–1.18, P = 0.01); eicosapentaenoic acid (EPA) (OR = 1.05, 95% CI:1.02–1.08, P = 0.001); and docosahexaenoic acid (DHA) (OR = 1.03, 95% CI:1.02–1.05, P<0.0001). Lignoceric acid is significantly associated with lower type 2 diabetes risk (OR = 0.95, 95% CI: 0.92–0.99, P = 0.01).

Conclusion

These data suggest that higher fasting whole blood concentrations of omega-6 polyunsaturated fatty acids (n-6PUFA) (ARA and DGLA) as well as omega-3 polyunsaturated fatty acid (n-3PUFA) (ALA, EPA, and DHA) are associated with an increased risk of diabetes, whereas increased fasting whole blood concentrations of lignoceric acid is inversely associated with diabetes risk.