Endoscopic Endonasal Approach in the Management of Rathke’s Cleft Cysts

Objective

Rathke’s cleft cysts (RCCs) are quite uncommon sellar lesions that can extend or even arise in the suprasellar area. The purpose of this study is to evaluate the effectiveness of both standard and extended endoscopic endonasal approaches in the management of different located RCCs.

Methods

We retrospectively analyzed a series of 29 patients (9 males, 20 females) complaining of a RCC, who underwent a standard or an extended endoscopic transsphenoidal approach at the Division of Neurosurgery, Department of Neurosciences and Reproductive and Odontostomatological Sciences, of the Università degli Studi di Napoli "Federico II”. Data regarding patients’ demographics, clinical evaluation, cyst characteristics, surgical treatments, complications and outcomes were extracted from our electronic database (Filemaker Pro 11, File Maker Inc., Santa Clara, California, USA).

Results

A standard transsphenoidal approach was used in 19 cases, while the extended variation of the approach in 10 cases (5 purely suprasellar and 5 intra-suprasellar RCC). Cysts contents was fully drained in all the 29 cases, whilst a gross total removal, that accounts on the complete cyst wall removal, was achieved in an overall 55,1% of patients (16/29), specifically 36,8% (7/19) that received standard approach and 90% (9/10) of those that underwent to extended approach. We reported a 56.2% of recovery from headache, 38.5% of complete recovery and 53.8% of improvement from visual field defect and an overall 46.7% of improvement of the endocrine functions. Postoperative permanent DI rate was 10.3%, overall post-operative CSF leak rate 6.9%; recurrence/regrowth occurred in 4 patients (4/29, 13.8%), but only one required a second surgery.

Conclusion

The endoscopic transsphenoidal approach for the removal of a symptomatic RCC offers several advantages in terms of visualization of the surgical field during both the exposure and removal of the lesion. The “extended” variation of the endoscopic approach provides a direct access to the supradiaphragmatic space, allowing adequate view and room for the safe removal of selected supradiaphragmatic RCCs, regardless of the sellar size (even a not enlarged sella), and provides a higher likelihood of preserving normal pituitary tissue and functions.     

Nasal Lipopolysaccharide Challenge and Cytokine Measurement Reflects Innate Mucosal Immune Responsiveness

Background

Practical methods of monitoring innate immune mucosal responsiveness are lacking. Lipopolysaccharide (LPS) is a component of the cell wall of Gram negative bacteria and a potent activator of Toll-like receptor (TLR)-4. To measure LPS responsiveness of the nasal mucosa, we administered LPS as a nasal spray and quantified chemokine and cytokine levels in mucosal lining fluid (MLF).

Methods

We performed a 5-way cross-over, single blind, placebo-controlled study in 15 healthy non-atopic subjects (n = 14 per protocol). Doses of ultrapure LPS (1, 10, 30 or 100μg/100μl) or placebo were administered by a single nasal spray to each nostril. Using the recently developed method of nasosorption with synthetic adsorptive matrices (SAM), a series of samples were taken. A panel of seven cytokines/chemokines were measured by multiplex immunoassay in MLF. mRNA for intercellular cell adhesion molecule-1 (ICAM-1) was quantified from nasal epithelial curettage samples taken before and after challenge.

Results

Topical nasal LPS was well tolerated, causing no symptoms and no visible changes to the nasal mucosa. LPS induced dose-related increases in MLF levels of IL-1β, IL-6, CXCL8 (IL-8) and CCL3 (MIP-1α) (AUC at 0.5 to 10h, compared to placebo, p<0.05 at 30 and 100μg LPS). At 100μg LPS, IL-10, IFN-α and TNF-α were also increased (p<0.05). Dose-related changes in mucosal ICAM-1 mRNA were also seen after challenge, and neutrophils appeared to peak in MLF at 8h. However, 2 subjects with high baseline cytokine levels showed prominent cytokine and chemokine responses to relatively low LPS doses (10μg and 30μg LPS).

Conclusions

Topical nasal LPS causes dose-dependent increases in cytokines, chemokines, mRNA and cells. However, responsiveness can show unpredictable variations, possibly because baseline innate tone is affected by environmental factors. We believe that this new technique will have wide application in the study of the innate immune responses of the respiratory mucosa.

Key Messages

Ultrapure LPS was used as innate immune stimulus in a human nasal challenge model, with serial sampling of nasal mucosal lining fluid (MLF) by nasosorption using a synthetic absorptive matrix (SAM), and nasal curettage of mucosal cells. A dose response could be demonstrated in terms of levels of IL-1β, IL-6, CXCL8 and CCL3 in MLF, as well as ICAM-1 mRNA in nasal curettage specimens, and levels of neutrophils in nasal lavage. Depending on higher baseline levels of inflammation, there were occasional magnified innate inflammatory responses to LPS.

Trial Registration

Clinical Trials.gov NCT02284074     

Characterization of Rhinitis According to the Asthma Status in Adults Using an Unsupervised Approach in the EGEA Study

Background

The classification of rhinitis in adults is missing in epidemiological studies.

Objective

To identify phenotypes of adult rhinitis using an unsupervised approach (data-driven) compared with a classical hypothesis-driven approach.

Methods

983 adults of the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) were studied. Self-reported symptoms related to rhinitis such as nasal symptoms, hay fever, sinusitis, conjunctivitis, and sensitivities to different triggers (dust, animals, hay/flowers, cold air…) were used. Allergic sensitization was defined by at least one positive skin prick test to 12 aeroallergens. Mixture model was used to cluster participants, independently in those without (Asthma-, n = 582) and with asthma (Asthma+, n = 401).

Results

Three clusters were identified in both groups: 1) Cluster A (55% in Asthma-, and 22% in Asthma+) mainly characterized by the absence of nasal symptoms, 2) Cluster B (23% in Asthma-, 36% in Asthma+) mainly characterized by nasal symptoms all over the year, sinusitis and a low prevalence of positive skin prick tests, and 3) Cluster C (22% in Asthma-, 42% in Asthma+) mainly characterized by a peak of nasal symptoms during spring, a high prevalence of positive skin prick tests and a high report of hay fever, allergic rhinitis and conjunctivitis. The highest rate of polysensitization (80%) was found in participants with comorbid asthma and allergic rhinitis.

Conclusion

This cluster analysis highlighted three clusters of rhinitis with similar characteristics than those known by clinicians but differing according to allergic sensitization, and this whatever the asthma status. These clusters could be easily rebuilt using a small number of variables.     

Testing Initiatives Increase Rates of HIV Diagnosis in Primary Care and Community Settings: An Observational Single-Centre Cohort Study

Objectives

The primary objective was to examine trends in new HIV diagnoses in a UK area of high HIV prevalence between 2000 and 2012 with respect to site of diagnosis and stage of HIV infection.

Design

Single-centre observational cohort study.

Setting

An outpatient HIV department in a secondary care UK hospital.

Participants

1359 HIV-infected adults.

Main Outcome Measures

Demographic information (age, gender, ethnicity, and sexual orientation), site of initial HIV diagnosis (Routine settings such as HIV/GUM clinics versus Non-Routine settings such as primary care and community venues), stage of HIV infection, CD4 count and seroconversion symptoms were collated for each participant.

Results

There was a significant increase in the proportion of new HIV diagnoses made in Non-Routine settings (from 27.0% in 2000 to 58.8% in 2012; p<0.001). Overall there was a decrease in the rate of late diagnosis from 50.7% to 32.9% (p=0.001). Diagnosis of recent infection increased from 23.0% to 47.1% (p=0.001). Of those with recent infection, significantly more patients were likely to report symptoms consistent with a seroconversion illness over the 13 years (17.6% to 65.0%; p<0.001).

Conclusions

This is the first study, we believe, to demonstrate significant improvements in HIV diagnosis and a shift in diagnosis of HIV from HIV/GUM settings to primary practice and community settings due to multiple initiatives.     

Indication for ‘Over the Scope’ (OTS)-Clip vs. Covered Self-Expanding Metal Stent (cSEMS) Is Unequal in Upper Gastrointestinal Leakage: Results from a Retrospective Head-to-Head Comparison

Background

Intestinal perforation or leakage increases morbidity and mortality of surgical and endoscopic interventions. We identified criteria for use of full-covered, extractable self-expanding metal stents (cSEMS) vs. ‘Over the scope’-clips (OTSC) for leak closure.

Methods

Patients who underwent endoscopic treatment for postoperative leakage, endoscopic perforation, or spontaneous rupture of the upper gastrointestinal tract between 2006 and 2013 were identified at four tertiary endoscopic centers. Technical success, outcome (e.g. duration of hospitalization, in-hospital mortality), and complications were assessed and analyzed with respect to etiology, size and location of leakage.

Results

Of 106 patients (male: 75 (71%), female: 31 (29%); age (mean ± SD): 62.5 ± 1.3 years, 72 (69%) were treated by cSEMS and 34 (31%) by OTSC. For cSEMS vs. OTSC, mean treatment duration was 41.1 vs. 25 days, p<0.001, leakage size 10 (1-50) vs. 5 (1-30) mm (median (range)), and complications were observed in 68% vs. 8.8%, p<0.001, respectively. Clinical success for primary interventional treatment was observed in 29/72 (40%) vs. 24/34 (70%, p = 0.006), and clinical success at the end of follow-up was 46/72 (64%) vs. 29/34 (85%) for patients treated by cSEMS vs. OTSC; p = 0.04.

Conclusion

OTSC is preferred in small-sized lesions and in perforation caused by endoscopic interventions, cSEMS in patients with concomitant local infection or abscess. cSEMS is associated with a higher frequency of complications. Therefore, OTSC might be preferred if technically feasible. Indication criteria for cSEMS vs. OTSC vary and might impede design of randomized studies.     

The Association of Gum Bleeding with Respiratory Health in a Population Based Study from Northern Europe

Background

There is little knowledge about how oral and respiratory health is interrelated even though the mucosa of the oral cavity and airways constitutes a continuum and the exposures to these are partly similar.

Aims

To investigate whether gum bleeding is related to asthma, respiratory symptoms and self-reported COPD.

Methods

A postal questionnaire including questions about respiratory and oral health was sent to general population samples in seven Northern European centres. In 13,409 responders, gum bleeding when brushing teeth was reported always/often by 4% and sometimes by 20%. Logistic regressions accounted for age, smoking, educational level, centre and gender. Effects of BMI, cardio-metabolic diseases, early life factors, gastro-oesophageal reflux, dental hygiene, nasal congestion, and asthma medication were addressed.

Results

Gum bleeding always/often was significantly associated with ≥3 asthma symptoms (OR 2.58, 95% CI 2.10–3.18), asthma (1.62 [1.23–2.14]) and self-reported COPD (2.02 [1.28–3.18]). There was a dose-response relationship between respiratory outcomes and gum bleeding frequency (≥3 symptoms: gum bleeding sometimes 1.42 [1.25–1.60], often/always 2.58 [2.10–3.18]), and there was no heterogeneity between centres (p_{heterogeneity} = 0.49). None of the investigated risk factors explained the associations. The observed associations were significantly stronger among current smokers (p_interaction = 0.004).

Conclusions

A consistent link between gum bleeding and obstructive airways disease was observed, not explained by common risk factors or metabolic factors. We speculate that oral pathogens might have unfavourable impact on the airways, and that the direct continuity of the mucosa of the oral cavity and the airways reflects a pathway that might provide novel opportunities for interventions.     

Effortless Attention as a Biomarker for Experienced Mindfulness Practitioners

Objective

The present study aimed at comparing frontal beta power between long-term (LTM) and first-time meditators (FTM), before, during and after a meditation session. We hypothesized that LTM would present lower beta power than FTM due to lower effort of attention and awareness.

Methods

Twenty one participants were recruited, eleven of whom were long-term meditators. The subjects were asked to rest for 4 minutes before and after open monitoring (OM) meditation (40 minutes).

Results

The two-way ANOVA revealed an interaction between the group and moment factors for the Fp1 (p<0.01), F7 (p = 0.01), F3 (p<0.01), Fz (p<0.01), F4 (p<0.01), F8 (p<0.01) electrodes.

Conclusion

We found low power frontal beta activity for LTM during the task and this may be associated with the fact that OM is related to bottom-up pathways that are not present in FTM.

Significance

We hypothesized that the frontal beta power pattern may be a biomarker for LTM. It may also be related to improving an attentive state and to the efficiency of cognitive functions, as well as to the long-term experience with meditation (i.e., life-time experience and frequency of practice).     

Effect of Body Mass Index and Intra-Abdominal Fat Measured by Computed Tomography on the Risk of Bowel Symptoms

Background

This study aims to investigate the association between body mass index (BMI) or intra-abdominal fat measured by computed tomography (CT) and bowel symptoms.

Method

A cohort of 958 Japanese adults who underwent colonoscopy and CT and completed questionnaires after excluding colorectal diseases was analyzed. Six symptoms (constipation, diarrhea, loose stools, hard stools, fecal urgency, and incomplete evacuation) using a 7-point Likert scale were evaluated between baseline and second questionnaire for test-retest reliability. Associations between BMI, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and symptom score were analyzed by a rank-ordered logistic model, adjusting for age, sex, smoking, and alcohol consumption, hypertension, diabetes mellitus, and dyslipidemia.

Results

Some bowel symptom scores were significantly (p<0.05) different between the age groups, sexes, smoking, and alcohol consumption. In multivariate analysis, constipation was associated with low BMI (p<0.01), low VAT area (p = 0.01), and low SAT area (p<0.01). Moreover, hard stools was associated with low BMI (p<0.01) and low SAT area (p<0.01). The remaining symptoms were not significantly associated with BMI or intra-abdominal fat. Test-retest reliability of bowel symptom scores with a mean duration of 7.5 months was good (mean kappa, 0.672).

Conclusions

Both low BMI and low abdominal fat accumulation appears to be useful indicators of increased risk for constipation and hard stools. The long-term test-retest reliability of symptom score suggests that bowel symptoms relevant to BMI or visceral fat remain consistent over several months.     

Efficacy of a Carrageenan nasal spray in patients with common cold: a randomized controlled trial

Background

The common cold is the most widespread viral infection in humans. Iota-carrageenan has previously shown antiviral effectiveness against cold viruses in clinical trials. This study investigated the efficacy of a carrageenan-containing nasal spray on the duration of the common cold and nasal fluid viral load in adult patients.

Methods

In a randomized, double-blind, placebo-controlled trial, 211 patients suffering from early symptoms of the common cold were treated for seven days. Application was performed three times daily with either a carrageenan-supplemented nasal spray or saline solution as placebo with an overall observation period of 21 days. The primary endpoint was the duration of disease defined as the time until the last day with symptoms followed by all other days in the study period without symptoms. During the study, but prior unblinding, the definition of disease duration was adapted from the original protocol that defines disease duration as the time period of symptoms followed by 48 hours without symptoms.

Results

In patients showing a laboratory-confirmed cold virus infection and adherence to the protocol, alleviation of symptoms was 2.1 days faster in the carrageenan group in comparison to placebo (p = 0.037). The primary endpoint that had been prespecified but was changed before unblinding was not met. Viral titers in nasal fluids showed a significantly greater decrease in carrageenan patients in the intention-to-treat population (p = 0.024) and in the per protocol population (p = 0.018) between days 1 and 3/4.

Conclusions

In adults with common cold virus infections, direct local administration of carrageenan with nasal sprays reduced the duration of cold symptoms. A significant reduction of viral load in the nasal wash fluids of patients confirmed similar findings from earlier trials in children and adults.

Trial registration

Current Controlled Trials ISRCTN80148028     

Effect of Diagnostic and Treatment Delay on the Risk of Tuberculosis Transmission in Shenzhen,China: An Observational Cohort Study, 1993–2010

Introduction

To understand better the risk of tuberculosis transmission with increasing delay in tuberculosis treatment, we undertook a retrospective cohort study in Shenzhen, China.

Methods

All pulmonary tuberculosis cases in the Shenzhen tuberculosis surveillance database from 1993–2010 were included. Sputum smear positivity and presence of pulmonary cavity were used as proxies for risk of tuberculosis transmission.

Results

Among 48,441pulmonary tuberculosis cases, 70% presented with symptoms of pulmonary TB, 62% were sputum smear positive, and 21% had a pulmonary cavity on chest x-ray. 95.3% of patients self-presented for evaluation of illness after a median 58 days of delay after symptoms began. The proportion presenting sputum smear positive (p<0.001) and with a pulmonary cavity (p<0.001) increased significantly with increasing duration of delay.

Conclusions

Delayed diagnosis and treatment of tuberculosis is associated with a significantly increased risk of pulmonary sputum smear positivity and pulmonary cavity. To decrease risk of transmission, treatment delay needs to be reduced further.     

Care Needs and Clinical Outcomes of Older People with Dementia: A Population-Based Propensity Score-Matched Cohort Study

Objective

To explore the healthcare resource utilization, psychotropic drug use and mortality of older people with dementia.

Design

A nationwide propensity score-matched cohort study.

Setting

National Health Insurance Research database.

Participants

A total of 32,649 elderly people with dementia and their propensity-score matched controls (n=32,649).

Measurements

Outpatient visits, inpatient care, psychotropic drug use, in-hospital mortality and all-cause mortality at 90 and 365 days.

Results

Compared to the non-dementia group, a higher proportion of patients with dementia used inpatient services (1 year after index date: 20.91% vs. 9.55%), and the dementia group had more outpatient visits (median [standard deviation]: 7.00 [8.87] vs. 3.00 [8.30]). Furthermore, dementia cases with acute admission had the highest psychotropic drug utilization both at baseline and at the post-index dates (difference-in-differences: all <0.001). Dementia was associated with an increased risk of all-cause mortality (90 days, Odds ratio (OR)=1.85 [95%CI 1.67-2.05], p<0.001; 365 days, OR=1.59 [1.50-1.69], p<0.001) and in-hospital mortality (90 days, OR=1.97 [1.71-2.27], p<0.001; 365 days, OR=1.82 [1.61-2.05], p<0.001) compared to matched controls.

Conclusions

When older people with dementia are admitted for acute illnesses, they may increase their use of psychotropic agents and their risk of death, particularly in-hospital mortality.     

Is Postoperative Imaging Mandatory after Meningioma Removal? Results of a Prospective Study

Background

Routine postoperative imaging (PI) following surgery for intracranial meningiomas is common practice in most neurosurgical departments. The purpose of this study was to determine the role of routine PI and its impact on clinical decision making after resection of meningioma.

Methods

Patient and tumor characteristics, details of radiographic scans, symptoms and alteration of treatment courses were prospectively collected for patients undergoing removal of a supratentorial meningioma of the convexity, falx, tentorium, or lateral sphenoid wing at the authors’ institution between January 1st, 2010 and March 31st, 2012. Patients with infratentorial manifestations or meningiomas of the skull base known to be surgically difficult (e.g. olfactory groove, petroclival, medial sphenoid wing) were not included. Maximum tumor diameter was divided into groups of < 3cm (small), 3 to 6 cm (medium), and > 6 cm (large).

Results

206 patients with meningiomas were operated between January 2010 and March 2012. Of these, 113 patients met the inclusion criteria and were analyzed in this study. 83 patients (73.5%) did not present new neurological deficits, whereas 30 patients (26.5%) became clinically symptomatic. Symptomatic patients had a change in treatment after PI in 21 cases (70%), while PI was without consequence in 9 patients (30%). PI did not result in a change of treatment in all asymptomatic patients (p<0.001) irrespective of tumor size (p<0.001) or localization (p<0.001).

Conclusions

PI is mandatory for clinically symptomatic patients but it is safe to waive it in clinically asymptomatic patients, even if the meningioma was large in size.     

Biodegradable Nasal Packings for Endoscopic Sinonasal Surgery: A Systematic Review and Meta-Analysis

Objectives

To assess biodegradable nasal packing effectiveness for improving postoperative symptoms and mucosal healing after endoscopic sinonasal surgery as compared with conventional/non-packing groups.

Methods

Relevant articles were searched on PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. We included randomized controlled trials (RCTs) that compared biodegradable packings with conventional packings or no packing, reporting postoperative symptoms and/or mucosal healing outcomes.

Results

This review included 19 studies, of which 11 compared biodegradable packings with conventional packings. Meta-analysis found that biodegradable packings significantly improved postoperative symptoms: bleeding at removal, pain at removal, pain in situ, and nasal blockage. Mucosal healing outcomes were inconsistent within studies, with no data could be pooled. Eight studies compared biodegradable packings with non-packing group. Postoperative symptom data in this comparison could not be pooled: A protective or equal effect on postoperative bleeding was reported in different studies; no difference was reported in pain status and nasal blockage. As for mucosal healing, meta-analysis showed that two arms of comparison had similar effect on synechiae, edema, infection and granulation at each time point.

Conclusion

The limiting evidence suggests that biodegradable nasal packings are statistically better than conventional packings in postoperative symptoms, and probably comparable to non-packing group, as in this comparison we could not carry out meta-analysis. No beneficial or detrimental effect on postoperative mucosal healing could be determined based on existing evidence.     

Hyaluronic Acid: Perspectives in Upper Aero-Digestive Tract. A Systematic Review

Background

To date, topical therapies guarantee a better delivery of high concentrations of pharmacologic agents to the mucosa of the upper aerodigestive tract (UADT). The use of topical drugs, which are able to reduce mucosal inflammation and to improve healing tissues, can represent a relevant therapeutic advance. Topical sodium hyaluronate (SH) has recently been recognized as adjuvant treatment in the chronic inflammatory disease of the UADT.

Aims

The aim of our work was to review the published literature regarding all the potential therapeutic effects of SH in the chronic inflammatory disease of UADT.

Methods

Relevant published studies were searched in Pubmed, Google Scholar, Ovid using keywords (“sodium hyaluronate” and “upper airways”) or Medical Subject Headings.

Results

At the end of our selection process, sixteen publications have been included. Six of them in the post-operative period of nasal-sinus surgery, 2 of them in pediatric patients affected by recurrent upper respiratory tract infections, 4 of them in reducing symptoms and preventing exacerbations of chronic upper airways in adult population, 4 of them in patients with chronic inflammatory disease of UADT, including gastro-esophageal reflux disease (GERD).

Conclusions

Topical administration of SH plays a pivotkey role in the postoperative phase of patients undergoing FESS and nasal surgery, and positive results are generally observed in all the patients suffering from UADT chronic inflammatory disease.     

Low Dose Infliximab for Prevention of Postoperative Recurrence of Crohn’s Disease: Long Term Follow-Up and Impact of Infliximab Trough Levels and Antibodies to Infliximab

Objective

In patients with postoperative recurrence of Crohn’s disease endoscopic and clinical remission can be maintained for up to 1 year with low infliximab doses (3 mg/Kg). However, in theory low-dose infliximab treated patients could develop subtherapeutic trough levels, infiximab antibodies, and might loose response to therapy. To verify this hypothesis infliximab pharmacokinetics and clinical/endoscopic response were checked in a group of patients treated in the long term with low infliximab doses.

Design

Infliximab antibodies, infliximab levels, highly-sensitive CRP and fecal calprotectin were measured during the 8-week interval in 5 consecutive patients in clinical (Crohn’s Disease Activity Index < 150) and endoscopic (Rutgeerts scores 0–1) remission after one year of therapy with infliximab 3 mg/Kg. For comparison with reported standards, infliximab pharmacokinetics and inflammatory parameters were also tested in 6 Crohn’s disease patients who did not undergo surgery and who were in clinical remission while on infliximab 5 mg/Kg. Patients on low infliximab dose also underwent colonoscopy after 18 additional months of therapy.

Results

Highly sensitive CRP and fecal calprotectin increased in all patients during the 8-week interval. Infliximab trough levels were lower in patients treated with the low dose compared to controls (mean±SE: 2.0±0.3 vs 4.75±0.83 μg/mL respectively p<0.05). Infliximab antibodies were present in two of the subjects treated with low infliximab dose and in none of the controls. However, in low dose-treated patients after 18 additional months of therapy endoscopy continued to show mucosal remission and none of them developed clinical recurrence or side effects.

Conclusions

Patients treated with low infliximab doses had lower trough levels compared to patients treated with 5 mg/Kg and some developed antibodies to infliximab. However, low infliximab doses sustained clinical and endoscopic remission for a total of 30 months of treatment.     

Ultrasound Echo-Intensity Predicts Severe Pancreatic Affection in Cystic Fibrosis Patients

Background

Pancreatic destruction affects the majority of patients with cystic fibrosis. We aimed to relate ultrasound findings to exocrine pancreatic function and cystic fibrosis genotype.

Methods

Patients with cystic fibrosis and a matched group of healthy controls were included. We performed transabdominal ultrasound, and recorded echo intensities of the pancreas and parenchymal characteristics according to endoscopic ultrasound based Rosemont criteria.

Results

We included 39 patients and 29 healthy controls. The cystic fibrosis patients were grouped according to exocrine pancreatic function; Cystic fibrosis, insufficient (n = 20) and sufficient (n = 19). Echo intensity measures and visual score demonstrated hyper-echogenicity in the pancreas insufficient group compared to the pancreas sufficient groups (p<0.001). Ductal and parenchymal changes were not prevalent in any of the groups.

Conclusion

The hyper-echoic pancreas was the most frequent ultrasonographic finding in exocrine pancreas insufficient cystic fibrosis patients. Pancreatic echo levels correlated to pancreatic phenotype.     

Abdominal Obesity and Brain Atrophy in Type 2 Diabetes Mellitus

Aim

Type 2 diabetes mellitus (T2D) is associated with gray matter atrophy. Adiposity and physical inactivity are risk factors for T2D and brain atrophy. We studied whether the associations of T2D with total gray matter volume (GMV) and hippocampal volume (HV) are dependent on obesity and physical activity.

Materials and Methods

In this cross-sectional study, we measured waist-hip ratio (WHR), body mass index (BMI), mean steps/day and brain volumes in a community dwelling cohort of people with and without T2D. Using multivariable linear regression, we examined whether WHR, BMI and physical activity mediated or modified the association between T2D, GMV and HV.

Results

There were 258 participants with (mean age 67±7 years) and 302 without (mean age 72±7 years) T2D. Adjusting for age, sex and intracranial volume, T2D was independently associated with lower total GMV (p = 0.001) and HV (p<0.001), greater WHR (p<0.001) and BMI (p<0.001), and lower mean steps/day (p = 0.002). After adjusting for covariates, the inclusion of BMI and mean steps/day did not significantly affect the T2D-GMV association, but WHR attenuated it by 32% while remaining independently associated with lower GMV (p<0.01). The T2D-HV association was minimally changed by the addition of BMI, steps/day or WHR in the model. No statistical interactions were observed between T2D and measures of obesity and physical activity in explaining brain volumes.

Conclusions

Abdominal obesity or its downstream effects may partially mediate the adverse effect of T2D on brain atrophy. This requires confirmation in longitudinal studies.     

Low Hemoglobin Level Is Associated with the Development of Delirium after Hepatectomy for Hepatocellular Carcinoma Patients

Background

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and liver resection is the only potential curative treatment option for those patients. Postoperative complications specific to elderly surgical patients such as delirium will be increasingly relevant in the coming decades. Herein, we aimed to investigate the risk factors for postoperative delirium in patients who have received hepatectomy for HCC.

Methods

This is a single medical center observational study and the study subjects comprised 401 individuals who underwent liver resection for hepatocellular carcinoma during January 2009 to October 2013. Multivariate analysis was used to examine whether preoperative, intra-operative, or postoperative variables were associated with the development of delirium.

Results

Of the 401 patients who underwent hepatectomy, 34 developed postoperative delirium (8.4%). In the majority of those patients, symptoms and signs of the syndrome occurred on postoperative day 2 and the mean duration of symptoms was 3.61 ± 3.71 days. Multivariate analysis revealed that advanced age (>71 years) [odds ratio (OR) = 1.133, 95% confidence interval (CI): 1.071–1.200, p<0.001], prolonged operative time (>190 minutes) (OR = 1.009, 95% CI: 1.000–1.017, p = 0.038), a decreased postoperative hemoglobin level (< 10.16 g/dL) (OR = 0.777, 95% CI: 0.613–0.983, p = 0.036), and history of hypnotic drug use (OR = 3.074, 95% CI: 1.045–9.039, p = 0.041) were independent risk factors for the development of postoperative delirium after hepatectomy.

Conclusions

Although the mechanism of postoperative delirium is not well understood, numbers of studies have shown that patients with postoperative delirium tend to have prolonged hospital stay, worse postoperative outcome and an increased risk of short- and long-term mortality. In this study, we found that advanced age, prolonged operative time, postoperative low hemoglobin level and history of hypnotic drug use are independent risk factors for postoperative delirium.     

Phenotyping of UGT1A1 Activity Using Raltegravir Predicts Pharmacokinetics and Toxicity of Irinotecan in FOLFIRI

Background

Irinotecan toxicity correlates with UGT1A1 activity. We explored whether phenotyping UGT1A1 using a probe approach works better than current genotyping methods.

Methods

Twenty-four Asian cancer patients received irinotecan as part of the FOLFIRI regimen. Subjects took raltegravir 400 mg orally and intravenous midazolam 1 mg. Pharmacokinetic analyses were performed using WinNonLin and NONMEM. Genomic DNA was isolated and screened for the known genetic variants in UGT1A1 and CYP3A4/5.

Results

SN-38G/SN-38 AUC ratio correlated well with Raltegravir glucuronide/ Raltegravir AUC ratio (r = 0.784 p<0.01). Midazolam clearance correlated well with irinotecan clearance (r = 0.563 p<0.01). SN-38 AUC correlated well with Log10Nadir Absolute Neutrophil Count (ANC) (r = -0.397 p<0.05). Significant correlation was found between nadir ANC and formation rate constant of raltegravir glucuronide (r = 0.598, P<0.005), but not UGT1A1 genotype.

Conclusion

Raltegravir glucuronide formation is a good predictor of nadir ANC, and can predict neutropenia in East Asian patients. Prospective studies with dose adjustments should be done to develop raltegravir as a probe to optimize irinotecan therapy.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00808184","term_id":"NCT00808184"}}NCT00808184     

Association of Mucosal Organisms with Patterns of Inflammation in Chronic Rhinosinusitis

Background

Chronic rhinosinusitis is a multifactorial process disease in which bacterial infection or colonization may play an important role in the initiation or persistence of inflammatory response. The association between mucosal bacteria presence and inflammatory patterns has only been partially explored.

Objective

To demonstrate specific mucosal microorganisms possible association with inflammatory patterns.

Methods

We collected nasal polyps or sinus tissues from a clinical selection of six patient groups with defined sinus disease using tissue biomarkers. In the tissues, we detected bacteria using peptide nucleic acid fluorescence in situ hybridization (PNA-FISH).

Results

After reviewing a total of 115 samples (15–20 samples per group), the mucosal presence of Staphylococcus aureus was correlated with IL-5 and SE-IgE positive chronic rhinosinusitis with nasal polyps and nasal polyps from cystic fibrosis patients. Chronic rhinosinusitis without nasal polyps with TNFα >20 pg/ml was associated with the mucosal presence of Pseudomonas aeruginosa.

Conclusion

This study identifies the relationship between intramucosal microbes and inflammatory patterns, suggesting that bacteria may affect the type of inflammation in chronic rhinosinusitis. Additional investigation is needed to further identify the nature of the relationship.