Predictive value of sleep apnea screenings in cardiac surgery patients.

INTRODUCTION: Obstructive sleep apnea (OSA) is a highly prevalent disorder associated with increased cardiovascular risks. We explored the predictive value of OSA screening instruments in cardiac disease patients awaiting cardiac surgery. METHODS: In this prospective cohort, 107 participants awaiting cardiac surgery from Cleveland Clinic and Johns Hopkins underwent polysomnography after completing Epworth Sleepiness Scale (ESS), Sleep Apnea/Sleep Disorder Questionnaire (SA/SDQ), STOP, STOPBAG2 and Berlin questionnaires. Score comparisons between groups based on apnea-hypopnea index (AHI) ≥15 were performed. Logistic regression with receiver operating characteristic (ROC) analysis was used to investigate optimal threshold. RESULTS: Prevalence of OSA (AHI ≥5) was 71.9% (77/107) and 51 (47.7%) had moderate-to-severe disease (AHI ≥15). Participants were primarily male (57%) and Caucasian (76.6%). Mean age was 67.3 ± 13.3 years and BMI was 26.5 ± 6.6. Of the five screening tools, STOPBAG2 with a cut-point of 0.381 provided 78% sensitivity and 38% specificity (AUC 0.66, 95%CI 0.55-0.77). SA/SDQ yielded a cut-point of 32 for all subjects (AUC: 0.62, 95%CI 0.51-0.73) with sensitivity and specificity of 60% and 62% respectively, while STOP score ≥2 provided sensitivity and specificity of 67% and 52% respectively (AUC: 0.61, 95%CI 0.51-0.72). Among STOP items, "observed apnea" had the strongest correlation with AHI ≥15 (OR 3.67, 95%CI 1.57-8.54, p = 0.003). The ESS and Berlin were not useful in identifying moderate-to-severe OSA. CONCLUSION: Common screening tools had suboptimal performance in cardiac surgery patients. STOPBAG2 was better at predicting the probability of moderate-to-severe OSA in patients undergoing cardiac surgery compared to ESS, SA/SDQ, STOP and Berlin questionnaires.

177Lu radiolabeling and preclinical theranostic study of 1C1m-Fc: an anti-TEM-1 scFv-Fc fusion protein in soft tissue sarcoma.

PURPOSE: TEM-1 (tumor endothelial marker-1) is a single-pass transmembrane cell surface glycoprotein expressed at high levels by tumor vasculature and malignant cells. We aimed to perform a preclinical investigation of a novel anti-TEM-1 scFv-Fc fusion antibody, 1C1m-Fc, which was radiolabeled with 177Lu for use in soft tissue sarcomas models. METHODS: 1C1m-Fc was first conjugated to p-SCN-Bn-DOTA using different excess molar ratios and labeled with 177Lu. To determine radiolabeled antibody immunoreactivity, Lindmo assays were performed. The in vivo behavior of [177Lu]Lu-1C1m-Fc was characterized in mice bearing TEM-1 positive (SK-N-AS) and negative (HT-1080) tumors by biodistribution and single-photon emission SPECT/CT imaging studies. Estimated organ absorbed doses were obtained based on biodistribution results. RESULTS: The DOTA conjugation and the labeling with 177Lu were successful with a radiochemical purity of up to 95%. Immunoreactivity after radiolabeling was 86% ± 4%. Biodistribution showed a specific uptake in TEM-1 positive tumor versus liver as critical non-specific healthy organ, and this specificity is correlated to the number of chelates per antibody. A 1.9-fold higher signal at 72 h was observed in SPECT/CT imaging in TEM-1 positive tumors versus control tumors. CONCLUSION: TEM-1 is a promising target that could allow a theranostic approach to soft-tissue sarcoma, and 1C1m-Fc appears to be a suitable targeting candidate. In this study, we observed the influence of the ratio DOTA/antibody on the biodistribution. The next step will be to investigate the best conjugation to achieve an optimal tumor-to-organ radioactivity ratio and to perform therapy in murine xenograft models as a prelude to future translation in patients.

Variations in radioiodine ablation: decision-making after total thyroidectomy.

BACKGROUND: The role of radioiodine treatment following total thyroidectomy for differentiated thyroid cancer is changing. The last major revision of the American Thyroid Association (ATA) Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer in 2015 changed treatment recommendations dramatically in comparison with the European Association of Nuclear Medicine (EANM) 2008 guidelines. We hypothesised that there is marked variability between the different treatment regimens used today. METHODS: We analysed decision-making in all Swiss hospitals offering radioiodine treatment to map current practice within the community and identify consensus and discrepancies. RESULTS AND CONCLUSION: We demonstrated that for low-risk DTC patients after thyroidectomy, some institutions offered only follow-up, while RIT with significant activities is recommended in others. For intermediate- and high-risk patients, radioiodine treatment is generally recommended. Dosing and treatment preparation (recombinant human thyroid stimulation hormone (rhTSH) vs. thyroid hormone withdrawal (THW)) vary significantly among centres.

GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: a potential neurogenetic pathway to panic disorder.

The molecular genetics of panic disorder (PD) with and without agoraphobia (AG) are still largely unknown and progress is hampered by small sample sizes. We therefore performed a genome-wide association study with a dimensional, PD/AG-related anxiety phenotype based on the Agoraphobia Cognition Questionnaire (ACQ) in a sample of 1370 healthy German volunteers of the CRC TRR58 MEGA study wave 1. A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRB gene (rs78726293, P=3.3 × 10-8; rs191260602, P=3.9 × 10-8). We followed up on this finding in a larger dimensional ACQ sample (N=2547) and in independent samples with a dichotomous AG phenotype based on the Symptoms Checklist (SCL-90; N=3845) and a case-control sample with the categorical phenotype PD/AG (Ncombined =1012) obtaining highly significant P-values also for GLRB single-nucleotide variants rs17035816 (P=3.8 × 10-4) and rs7688285 (P=7.6 × 10-5). GLRB gene expression was found to be modulated by rs7688285 in brain tissue, as well as cell culture. Analyses of intermediate PD/AG phenotypes demonstrated increased startle reflex and increased fear network, as well as general sensory activation by GLRB risk gene variants rs78726293, rs191260602, rs17035816 and rs7688285. Partial Glrb knockout mice demonstrated an agoraphobic phenotype. In conjunction with the clinical observation that rare coding GLRB gene mutations are associated with the neurological disorder hyperekplexia characterized by a generalized startle reaction and agoraphobic behavior, our data provide evidence that non-coding, although functional GLRB gene polymorphisms may predispose to PD by increasing startle response and agoraphobic cognitions.

Strength and ductility with {10͞11} - {10͞12} double twinning in a magnesium alloy.

Based on their high specific strength and stiffness, magnesium alloys are attractive for lightweight applications in aerospace and transportation, where weight saving is crucial for the reduction of carbon dioxide emissions. Unfortunately, the ductility of magnesium alloys is usually limited. It is thought that one reason for the lack of ductility is that the development of - double twins (DTW) cause premature failure of magnesium alloys. Here we show with a magnesium alloy containing 4 wt% lithium, that the same impressively large compression failure strains can be achieved with DTWs as without. The DTWs form stably across the microstructure and continuously throughout straining, forming three-dimensional intra-granular networks, a potential strengthening mechanism. We rationalize that relatively easier slip characteristic of this alloy plastically relaxed the localized stress concentrations that DTWs can generate. This result may provide key insight and an alternative perspective towards designing formable and strong magnesium alloys.

Intestinal regeneration, residual function and immunological priming following rescue therapy after rat small bowel transplantation.

Clinical evidence suggests that recurrent acute cellular rejection (ACR) may trigger chronic rejection and impair outcome after intestinal transplantation. To test this hypothesis and clarify underlying molecular mechanisms, orthotopic/allogenic intestinal transplantation was performed in rats. ACR was allowed to occur in a MHC-disparate combination (BN-LEW) and two rescue strategies (FK506monotherapy vs. FK506+infliximab) were tested against continuous immunosuppression without ACR, with observation for 7/14 and 21 days after transplantation. Both, FK506 and FK506+infliximab rescue therapy reversed ACR and resulted in improved histology and less cellular infiltration. Proinflammatory cytokines and chemotactic mediators in the muscle layer were significantly reduced in FK506 treated groups. Increased levels of CD4, FOXP3 and IL-17 (mRNA) were observed with infliximab. Contractile function improved significantly after FK506 rescue therapy, with a slight benefit from additional infliximab, but did not reach nontransplanted controls. Fibrosis onset was detected in both rescue groups by Sirius-Red staining with concomitant increase of the fibrogenic mediator VEGF. Recovery from ACR could be attained by both rescue therapy regimens, progressing steadily after initiation of immunosuppression. Reversal of ACR, however, resulted in early stage graft fibrosis. Additional infliximab treatment may enhance physiological recovery of the muscle layer and enteric nervous system independent of inflammatory reactions.

Perioperative infliximab application has marginal effects on ischemia-reperfusion injury in experimental small bowel transplantation in rats.

PURPOSE: Ischemia-reperfusion injury leads to impaired smooth muscle function and inflammatory reactions after intestinal transplantation. In previous studies, infliximab has been shown to effectively protect allogenic intestinal grafts in the early phase after transplantation with resulting improved contractility. This study was designed to reveal protective effects of infliximab on ischemia-reperfusion injury in isogenic transplantation. METHODS: Isogenic, orthotopic small bowel transplantation was performed in Lewis rats (3 h cold ischemia). Five groups were defined: non-transplanted animals with no treatment (group 1), isogenic transplanted animals with vehicle treatment (groups 2/3) or with infliximab treatment (5 mg/kg body weight intravenously, directly after reperfusion; groups 4/5). The treated animals were sacrificed after 3 (group 2/4) or 24 h (group 3/5). Histological and immunohistochemical analysis, TUNEL staining, real-time RT-PCR, and contractility measurements in a standard organ bath were used for determination of ischemia-reperfusion injury. RESULTS: All transplanted animals showed reduced smooth muscle function, while no significant advantage of infliximab treatment was observed. Reduced infiltration of neutrophils was noted in the early phase in animals treated with infliximab. The structural integrity of the bowel and infiltration of ED1-positive monocytes and macrophages did not improve with infliximab treatment. At 3 h after reperfusion, mRNA expression of interleukin (IL)-6, TNF-α, IL-10, and iNOS and MCP-1 displayed increased activation in the infliximab group. CONCLUSION: The protective effects of infliximab in the early phase after experimental small bowel transplantation seem to be unrelated to ischemia-reperfusion injury. The promising effects in allogenic transplantation indicate the need for further experiments with infliximab as complementary treatment under standard immunosuppressive therapy. Further experiments should focus on additional infliximab treatment in the setting of acute rejection.

Perioperative infliximab application ameliorates acute rejection associated inflammation after intestinal transplantation.

As we have shown in the past, acute rejection-related TNF-α upregulation in resident macrophages in the tunica muscularis after small bowel transplantation (SBTx) results in local amplification of inflammation, decisively contributing to graft dysmotility. Therefore, the aim of this study is to investigate the effectiveness of the chimeric-monoclonal-anti-TNF-α antibody infliximab as perioperative single shot treatment addressing inflammatory processes during acute rejection early after transplantation. Orthotopic, isogenic and allogenic SBTx was performed in rats (BN-Lewis/BN-BN) with infliximab treatment. Vehicle and IV-immunoglobulin-treated animals served as controls. Animals were sacrificed after 24 and 168 h. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry, mediator mRNA expression by Real-Time-RT-PCR, apoptosis by TUNEL and smooth muscle contractility in a standard organ bath. Both, infliximab and Sandoglobulin® revealed antiinflammatory effects. Infliximab resulted in significantly less leukocyte infiltration compared to allogenic controls and IV-immunoglobulin, which was accompanied by lower gene expression of MCP-1 (24 h), IFN-γ (168 h) and infiltration of CD8-positive cells. Smooth muscle contractility improved significantly after 24 h compared to all controls in infliximab treated animals accompanied by lower iNOS expression. Perioperative treatment with infliximab is a possible pharmaceutical approach to overcome graft dysmotility early after SBTx.

Influence of immunosuppression on alloresponse, inflammation and contractile function of graft after intestinal transplantation.

In small bowel transplantation (SBTx), graft manipulation, ischemia/reperfusion injury and acute rejection initiate a severe cellular and molecular inflammatory response in the muscularis propria leading to impaired motility of the graft. This study examined and compared the effect of tacrolimus and sirolimus on inflammation in graft muscularis. After allogeneic orthotopic SBTx, recipient rats were treated with tacrolimus or sirolimus. Tacrolimus and sirolimus attenuated neutrophilic, macrophage and T-cell infiltration in graft muscularis, which was associated with reduced apoptotic cell death. Nonspecific inflammatory mediators (IL-6, MCP-1) and T-cell activation markers (IL-2, IFN-gamma) were highly upregulated in allogeneic control graft muscularis 24 h and 7 days after SBTx, and tacrolimus and sirolimus significantly suppressed upregulation of these mediators. In vitro organ bath method demonstrated a severe decrease in graft smooth muscle contractility in allogeneic control (22% of normal control). Correlating with attenuated upregulation of iNOS, tacrolimus and sirolimus treatment significantly improved contractility (64% and 72%, respectively). Although sirolimus reduced cellular and molecular inflammatory response more efficiently after 24 h, contrary tacrolimus prevented acute rejection more efficiently. In conclusion, tacrolimus and sirolimus attenuate cellular and molecular inflammatory response in graft muscularis and subsequent dysmotility of the graft after allogeneic SBTx.

Energy transfer, volumetric expansion, and removal of oral biofilms by non-contact brushing.

Non-contact removal of oral biofilms offers advantages beyond the reach of bristles, but it is unknown how energy transfer for removal from brush-to-biofilm occurs. In the present study we evaluated non-contact, oral biofilm removal by oscillating-rotating and sonic toothbrushes, and their acoustic output up to 6 mm distance. Whereas some brushes removed biofilm when used at a distance of up to 6 mm, others lost efficacy at a distance of 2-4 mm from the biofilm. Loss of efficacy was accompanied with high standard deviations and volumetric biofilm expansion. Both sonic and oscillating-rotating brushes caused fluid flows and the inclusion of air-bubbles, while non-contact acoustic energy-transfer was demonstrated to decay with distance for both types of brushes. We put forward the following mechanism for non-contact removal: (i) brush energy is absorbed by biofilm, resulting in the visco-elastic expansion of the biofilm; (ii) if the energy absorbed is sufficient and deformation is beyond the yield point, biofilm removal occurs; and (iii) if deformation is in the plastic range but below the yield point (i.e. at the limiting distance for non-contact removal), biofilm is expanded but not removed.

Risk-adapted FDG-PET/CT-based follow-up in patients with diffuse large B-cell lymphoma after first-line therapy.

BACKGROUND: The purpose of this study was to evaluate the impact of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) during follow-up of patients with diffuse large B-cell lymphoma (DLBCL) being in complete remission or unconfirmed complete remission after first-line therapy. PATIENTS AND METHODS: DLBCL patients receiving FDG-PET/CT during follow-up were analyzed retrospectively. Confirmatory biopsy was mandatory in cases of suspected disease recurrence. RESULTS: Seventy-five patients were analyzed and 23 (30%) had disease recurrence. The positive predictive value (PPV) of FDG-PET/CT was 0.85. Patients >60 years [P = 0.036, hazard ratio (HR) = 3.82, 95% confidence interval (CI) 1.02-7.77] and patients with symptoms indicative of a relapse (P = 0.015; HR = 4.1; 95% CI 1.20-14.03) had a significantly higher risk for relapse. A risk score on the basis of signs of relapse, age >60 years, or a combination of these factors identified patients at high risk for recurrence (P = 0.041). CONCLUSIONS: FDG-PET/CT detects recurrent DLBCL after first-line therapy with high PPV. However, it should not be used routinely and if only in selected high-risk patients to reduce radiation burden and costs. On the basis of our retrospective data, FDG-PET/CT during follow-up is indicated for patients <60 years with clinical signs of relapse and in patients >60 years with and without clinical signs of relapse.

Hodgkin's lymphoma in remission after first-line therapy: which patients need FDG-PET/CT for follow-up?

BACKGROUND: The purpose of the study was to evaluate the impact of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/computed tomography (CT) during follow-up of patients with Hodgkin's lymphoma. PATIENTS AND METHODS: Patients in complete remission or an unconfirmed complete remission after first-line therapy who received FDG-PET/CT during their follow-up were analyzed retrospectively. Confirmatory biopsy was mandatory in case of recurrence. RESULTS: Overall, 134 patients were analyzed. Forty-two (31.3%) patients had a recurrence. The positive predictive value of FDG-PET/CT was 0.98. Single-factor analysis identified morphological residual mass [P = 0.0005, hazard ratio (HR) 3.4, 95% confidence interval (CI) 1.7-6.6] and symptoms (P < 0.0001, HR 4.9, 95% CI 2.4-9.9) as significant risk factors for relapse. By multivariate analysis, morphological residual mass was the only significant risk factor for early follow-up (<24 months) (P = 0.0019, HR 7.6, 95% CI 2.1-27.3). Advanced stage (P = 0.0426, HR 3.6, 95% CI 1.1-12.3) and the presence of symptoms (P = 0.0009, HR = 14.6, 95% CI 3.0-69.7) were found to be significant risk factors for later follow-up (>24 months). CONCLUSIONS: Asymptomatic patients without morphological residues and an early stage of disease do not need a routine FDG-PET/CT for follow-up. Asymptomatic patients with morphological residues should receive routine follow-up FDG-PET/CT for the first 24 months. Only patients with advanced initial stage do need a routine follow-up FDG-PET/CT beyond 24 months.

Treating obstructive sleep apnea in adults with epilepsy: a randomized pilot trial.

OBJECTIVE: Small uncontrolled series suggest that treatment of obstructive sleep apnea (OSA) in patients with epilepsy may improve seizure control. Prior to conducting a definitive randomized controlled trial, we addressed critical design issues in a pilot study. METHODS: We identified a cohort of adult patients with medically refractory epilepsy and coexisting OSA, documented by polysomnography (PSG). After an 8-week baseline period, subjects with OSA were randomized to therapeutic or sham continuous positive airway pressure (CPAP) for 10 weeks. Subjects maintained seizure calendars and antiepileptic drug dosages were held constant. RESULTS: Sixty-eight subjects with suspected OSA were enrolled and 35 subjects randomized to therapeutic CPAP (22 subjects) or sham (13 subjects) CPAP. Male gender and an elevated sleep apnea questionnaire score were predictive of OSA on PSG. Nineteen subjects in the therapeutic group and all 13 subjects in the sham group completed the trial. Baseline apnea-hypopnea index (AHI) and CPAP adherence were comparable between groups. A significant reduction in AHI was observed in the therapeutic CPAP group as compared to the sham group. Subjects, study coordinators, and principal investigators were unable to predict treatment allocation. CONCLUSIONS: This pilot study provided critical information related to study design and feasibility for planning a comprehensive trial to test the hypothesis that treating obstructive sleep apnea in patients with epilepsy improves seizure control.

Influence of temporary abdominal wall repair on the intestinal integrity: an experimental study in the rat.

BACKGROUND AND AIMS: The aim of this study was to analyze intestinal integrity after temporary abdominal wall repair with absorbable mesh. METHODS: Rats underwent abdominal wall repair with absorbable mesh or sham operation. Myeloperoxidase-positive cells in the intestinal muscularis were histochemically quantified. Intestinal transit was visualized 48 h after surgery. Local and systemic inflammatory response was measured with TNF-alpha and IL-6 ELISA as well as malondialdehyde (MDA) expression in serum and peritoneal fluid. RESULTS: Neutrophil count of the intestinal muscularis revealed that infiltration in the mesh-implanted and in the mesh-free animals 48 h postoperatively was similar. Gastrointestinal transit was similarly unaffected 48 h after surgery, with or without mesh implantation. TNF-alpha, IL-6 and MDA concentration in serum and peritoneal fluid showed no significant differences between the two groups. CONCLUSION: Intestinal contractility and local and systemic inflammatory response remained unaffected. Therefore, absorbable mesh augmentation is a safe and reliable method for temporary repair of the abdominal wall without affecting the intestinal integrity.

Video-electrographic and clinical features in patients with ictal asystole.

OBJECTIVE: Ictal asystole (IA) is a rare event mostly seen in patients with temporal lobe epilepsy (TLE) and a potential contributor to sudden unexplained death in epilepsy (SUDEP). Clinical and video-electroencephalographic findings associated with IA have not been described, and may be helpful in screening for high risk patients. METHODS: A database search was performed of 6,825 patients undergoing long-term video-EEG monitoring for episodes of IA. RESULTS: IA was recorded in 0.27% of all patients with epilepsy, eight with temporal (TLE), two with extratemporal (XTLE), and none with generalized epilepsy. In 8 out of 16 recorded events, all occurring in patients with TLE, seizures were associated with a sudden atonia on average 42 seconds into the typical semiology of a complex partial seizure. The loss of tone followed after a period of asystole usually lasting longer than 8 seconds and was associated with typical EEG changes seen otherwise with cerebral hypoperfusion. Clinical predisposing factors for IA including cardiovascular risk factors or baseline ECG abnormalities were not identified. CONCLUSION: Ictal asystole is a rare feature of patients with focal epilepsy. Delayed loss of tone is distinctly uncommon in patients with temporal lobe seizures, but may inevitably occur in patients with ictal asystole after a critical duration of cardiac arrest and cerebral hypoperfusion. Further cardiac monitoring in patients with temporal lobe epilepsy and a history of unexpected collapse and falls late in the course of a typical seizure may be warranted and can potentially help to prevent sudden unexplained death in epilepsy.

Resident macrophages are involved in intestinal transplantation-associated inflammation and motoric dysfunction of the graft muscularis.

Gut manipulation and ischemia/reperfusion evoke an inflammatory response within the intestinal muscularis that contributes to dysmotility. We hypothesize that resident macrophages play a key role in initiating the inflammatory cascade. Isogenic small bowel transplantation was performed in Lewis rats. The impact of recovery of organs on muscularis inflammation was investigated by comparing cold whole-body perfusion after versus prior to recovery. The role of macrophages was investigated by transplantation of macrophage-depleted gut. Leukocytes were counted using muscularis whole mounts. Mediator expression was determined by real-time RT-PCR. Contractility was assessed in a standard organ bath. Both organ recovery and ischemia/reperfusion induced leukocyte recruitment and a significant upregulation in IL-6, MCP-1, ICAM-1 and iNOS mRNAs. Although organ recovery in cold ischemia prevented early gene expression, peak expression was not changed by modification of the recovery technique. Compared to controls, transplanted animals showed a 65% decrease in smooth muscle contractility. In contrast, transplanted macrophage-depleted isografts exhibited significant less leukocyte infiltration and only a 19% decrease in contractile activity. In summary, intestinal manipulation during recovery of organs initiates a functionally relevant inflammatory response within the intestinal muscularis that is massively intensified by the ischemia reperfusion injury. Resident muscularis macrophages participate in initiating this inflammatory response.

Cost-effective therapy remission assessment in lymphoma patients using 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography: is an end of treatment exam necessary in all patients?

BACKGROUND: The aim of this study was to evaluate the necessity of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) after end of treatment in lymphoma patients who had an interim FDG-PET/CT. PATIENTS AND METHODS: In 38 patients with Hodgkin's disease (HD) and 30 patients with non-Hodgkin's lymphoma (NHL) interim PET/CT (intPET) after two to four cycles of chemotherapy and PET/CT after completion of first-line treatment (endPET) were carried out. Cost reduction was retrospectively calculated for the potentially superfluous endPET examinations. RESULTS: In 31 (82%) HD patients, intPET demonstrated complete remission (CR) which was still present on endPET. The remaining seven HD patients (18%) had partial remission (PR) on intPET. For NHL, 22 (73%) patients had CR on intPET analysis which was still present on endPET. In the remaining eight NHL patients, intPET revealed PR in seven and stable disease in one patient. None of all intPET complete responders progressed until the end of therapy. Thus, of the 196 PET/CT's carried out in our study population, 53 endPET's (27.0%) were carried out in interim complete responders. CONCLUSION: End-treatment PET/CT is unnecessary if intPET shows CR and the clinical course is uncomplicated. An imaging cost reduction of 27% in our study population could have been achieved by omitting end of treatment FDG-PET/CT in interim complete responders.

Health-related quality of life in patients with obstructive sleep apnoea and chronic obstructive pulmonary disease (overlap syndrome).

The association of obstructive sleep apnoea (OSA) and chronic obstructive pulmonary disease (COPD) is not rare as COPD and OSA are both frequent diseases. The aim of this study was to determine the effect of OSA on quality of life (QOL) in patients with overlap syndrome (OVS). Thirty subjects with OVS and 15 control subjects participated. The St George's Respiratory Questionnaire (SGRQ) was used to determine QOL. The control group included subjects with COPD and no evidence of OSA by overnight polysomnography. All subjects were habitual snorers with normal Epworth Sleepiness Scale scores. Significant differences were found between the groups for the total score and each of the three components of the SGRQ suggesting worse QOL in OVS patients (symptoms 54.9 +/- 18.9 vs. 38.2 +/- 19.3, p = 0.008; activity 59.2 +/- 16.2 vs. 44.4 +/- 11.3, p = 0.003; impacts 35.2 +/- 23 vs. 20.8 +/- 8.7, p = 0.025 and total 45.7 +/- 17.7 vs. 30.9 +/- 8.7, p = 0.004 in OVS patients and control group, respectively). Obstructive sleep apnoea has a major impact on QOL in patients with OVS and can exist in COPD patients with habitual snoring even in the absence of daytime sleepiness. Further studies are needed to determine the impact of OSA treatment on QOL and morbidity in this population.

Gastric stump carcinoma - epidemiology and current concepts in pathogenesis and treatment.

AIM: The aim of this article is to review the aetiology, pathology and treatment of gastric stump carcinoma (GSC). GSC is an uncommon tumour; however, the incidence is not declining, so this tumour entity will be encountered in the years to come. METHODS: The electronic literature search was performed in the MEDLINE database to identify relevant studies concerning epidemiology, prognosis, treatment, aetiology and pathology of GSC. The references reported in these studies were used to complete the literature search. RESULTS: Patients subjected to distal gastric resection have a 4-7-fold increased risk of developing GSC, which is attributed mainly to gastroduodenal reflux. Denervation during partial gastrectomy may also contribute to the risk of developing GSC. Gastroduodenal ulcers were the main reason for partial gastrectomy. Both ulcer locations have an increased risk of developing GSC after 20 years. In GSC, Helicobacter pylori seems not to be an important risk factor, contrary to primary gastric cancer, because gastroduodenal reflux impairs the growth of Helicobacter pylori. CONCLUSION: The treatment of choice for GSC should be the total removal of the gastric remnant including at least D2 lymphadenectomy. The pattern of lymph node metastases in GSC may differ from primary gastric cancer, as lymph node metastases have been reported in the jejunal mesentery and the lower mediastinum. Therefore, GSC may require a modified lymphadenectomy to include all important lymph node stations. After radical remnant gastrectomy, GSC has a prognosis not different from primary proximal gastric cancer.

Improved efficiency of budesonide nebulization using surface-active agents.

Our aim was to improve the efficiency of nebulised budesonide using surface-active agents. Cationic, anionic, and nonionic detergents were added to commercial budesonide suspension, and the particle size distribution during nebulization was measured using both cascade impaction and laser diffraction. Our results showed that the emitted dose was increased after addition of cationic (p < 0.001) and nonionic detergents (p < 0.01) compared with the commercial formulation alone. The respirable fraction was increased for all detergent formulations (p < 0.001) compared with the commercial formulation. We concluded that cationic and nonionic detergent increased the total output of budesonide from the Sidestream. All detergent formulations increased the respirable fraction of nebulized budesonide.