The EUFOREA pocket guide for chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is known to affect around 5 % of the total population, with major impact on the quality of life of those severely affected (1). Despite a substantial burden on individuals, society and health economies, CRS often remains underdiagnosed, under-estimated and under-treated (2). International guidelines like the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) (3) and the International Consensus statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR) (4) offer physicians insight into the recommended treatment options for CRS, with an overview of effective strategies and guidance of diagnosis and care throughout the disease journey of CRS.

Correction to: Measuring and understanding adherence in a home-based exercise intervention during chemotherapy for early breast cancer.

In the original publication, the sixth author name was published incorrectly as A. Wood. The correct author name should read as W. A. Wood.

Impact of a multicarbohydrase containing α-galactosidase and xylanase on ileal digestible energy, crude protein digestibility, and ileal amino acid digestibility in broiler chickens.

Exogenous enzymatic supplementation of poultry feeds, including α-galactosidase and xylanase, has been shown to increase metabolically available energy, although little information has been published on the impact on amino acid digestibility. An experiment was conducted to investigate a multicarbohydrase containing α-galactosidase and xylanase on amino acid digestibility, ileal digestible energy (IDE), and CP in male broiler chicks. The experiment was a 2 × 2 (diet × enzyme) factorial arrangement with 15 replicates of 8 male broilers per replicate raised for 21 d in a battery setting. The 2 dietary treatments included a positive control (PC) and a negative control (NC) diet formulated to contain 2.5% less calculated AME and digestible amino acids. Each of these diets was fed with and without enzyme. Broilers were fed a starter diet from 0-14 d (crumble) and a grower from 14-21 d (pellet). Birds were sampled on day 21 to determine ileal amino acid digestibility, IDE, and CP digestibility. Titanium dioxide (TiO2) was used as an indigestible marker for the determination of digestibility coefficients. Total ileal amino acid digestibility was increased (P = 0.008) by 3.80% with the inclusion of enzyme. Methionine and lysine digestibility was improved (P < 0.05) with the inclusion of enzyme by 3.37% and 2.61%, respectively. Enzyme inclusion increased (P = 0.001) cysteine digestibility by 9.3%. Diet-influenced ileal amino acid digestibility with tryptophan, threonine, isoleucine, and valine digestibility being increased (P < 0.05) in the PC when compared to the NC. IDE was decreased (P = 0.037) in broilers fed the NC diet by 100 kcal/kg feed when compared to broilers fed the PC diet. Enzyme inclusion increased (P = 0.047) IDE value by 90 kcal/kg. Crude protein digestibility was not influenced by diet; however, similar improvements in CP digestibility with enzyme inclusion were observed as with energy. These data support the benefits of a multicarbohydrase containing α-galactosidase and xylanase inclusion to improve nutrient and ileal amino acid digestibility across multiple dietary nutrient profiles.

Measuring and understanding adherence in a home-based exercise intervention during chemotherapy for early breast cancer.

PURPOSE: Ensuring and measuring adherence to prescribed exercise regimens are fundamental challenges in intervention studies to promote exercise in adults with cancer. This study reports exercise adherence in women who were asked to walk 150 min/week throughout chemotherapy treatment for early breast cancer. Participants were asked to wear a FitbitTM throughout their waking hours, and Fitbit steps were uploaded directly into study computers. METHODS: Descriptive statistics are reported, and both unadjusted and multivariable linear regression models were used to assess associations between participant characteristics, breast cancer diagnosis, treatment, chemotherapy toxicities, and patient-reported symptoms with average Fitbit steps/week. RESULTS: Of 127 women consented to the study, 100 had analyzable Fitbit data (79%); mean age was 48 and 31% were non-white. Mean walking steps were 3956 per day. Nineteen percent were fully adherent with the target of 6686 steps/day and an additional 24% were moderately adherent. In unadjusted analysis, baseline variables associated with fewer Fitbit steps were: non-white race (p = 0.012), high school education or less (p = 0.0005), higher body mass index (p = 0.0024), and never/almost never drinking alcohol (p = 0.0048). Physical activity variables associated with greater Fitbit steps were: pre-chemotherapy history of vigorous physical activity (p = 0.0091) and higher self-reported walking minutes/week (p < 0.001), and higher outcome expectations from exercise (p = 0.014). Higher baseline anxiety (p = 0.03) and higher number of chemotherapy-related symptoms rates "severe/very severe" (p = 0.012) were associated with fewer steps. In multivariable analysis, white race was associated with 12,146 greater Fitbit steps per week (p = 0.004), as was self-reported walking minutes prior to start of chemotherapy (p < 0.0001). CONCLUSIONS: Inexpensive commercial-grade activity trackers, with data uploaded directly into research computers, enable objective monitoring of home-based exercise interventions in adults diagnosed with cancer. Analysis of the association of walking steps with participant characteristics at baseline and toxicities during chemotherapy can identify reasons for low/non-adherence with prescribed exercise regimens.

The potential impact of sleep-related movement disorders on stroke risk: a population-based longitudinal study.

BACKGROUND: Sleep-related movement disorders (SRMD) have been shown to increase the risk of cardiovascular diseases. However, the relationship between SRMD and stroke remains unclear. AIM: To explore the relationship between SRMD and stroke in the general population. DESIGN: Two cohorts of patients with SRMD and without SRMD were followed up for the occurrence of hemorrhagic and ischemic stroke. METHODS: The study cohort enrolled 604 patients who were initially diagnosed as SRMD between 2000 and 2005. 2,416 age- and sex-matched patients without prior stroke were selected as the comparison cohort. A Cox-proportional hazard regression analysis was performed for multivariate adjustment. RESULTS: Patients with SRMD had a higher risk for developing all-cause stroke [adjusted hazard ratio (HR) = 2.29, 95% confidence interval (CI) = 1.42-3.80]. Patients of below 45 years old had the greatest stroke risk (HR = 4.03, 95% CI = 3.11-5.62), followed by patients aged ≥65 years (HR = 2.64, 95% CI = 1.12-3.44) and 45-64 years (HR = 1.07, 95% CI = 1.02-1.71). The age-stratified analysis suggested that the increased risk of hemorrhagic stroke was more significant than ischemic stroke among all age groups. Furthermore, males with SRMD were at greater risk to develop all-cause stroke (HR = 2.98, 95% CI = 1.74-4.50) than that of females (HR = 1.94, 95% CI = 1.01-3.77). CONCLUSIONS: Patients with SRMD were found to have an increased risk of all-cause stroke along with a higher possibility of hemorrhagic stroke over ischemic stroke.

A CpG island methylator phenotype in acute myeloid leukemia independent of IDH mutations and associated with a favorable outcome.

Genetic changes are infrequent in acute myeloid leukemia (AML) compared with other malignancies and often involve epigenetic regulators, suggesting that an altered epigenome may underlie AML biology and outcomes. In 96 AML cases including 65 pilot samples selected for cured/not-cured, we found higher CpG island (CGI) promoter methylation in cured patients. Expanded genome-wide digital restriction enzyme analysis of methylation data revealed a CGI methylator phenotype independent of IDH1/2 mutations we term AML-CGI methylator phenotype (CIMP) (A-CIMP+). A-CIMP was associated with longer overall survival (OS) in this data set (median OS, years: A-CIMP+=not reached, CIMP-=1.17; P=0.08). For validation we used 194 samples from The Cancer Genome Atlas interrogated with Illumina 450k methylation arrays where we confirmed longer OS in A-CIMP (median OS, years: A-CIMP+=2.34, A-CIMP-=1.00; P=0.01). Hypermethylation in A-CIMP+ favored CGIs (OR: CGI/non-CGI=5.21), and while A-CIMP+ was enriched in CEBPA (P=0.002) and WT1 mutations (P=0.02), 70% of cases lacked either mutation. Hypermethylated genes in A-CIMP+ function in pluripotency maintenance, and a gene expression signature of A-CIMP was associated with outcomes in multiple data sets. We conclude that CIMP in AML cannot be explained solely by gene mutations (for example, IDH1/2, TET2), and that curability in A-CIMP+ AML should be validated prospectively.

Five Year Outcomes of Surgical Treatment for Popliteal Artery Entrapment Syndrome.

OBJECTIVE/BACKGROUND: The aim of this study was to evaluate long-term outcomes following surgery for popliteal artery entrapment syndrome. METHODS: A retrospective study of all patients that underwent surgery for popliteal artery entrapment syndrome between January 2003 and December 2009 was performed. Patient demographic data, clinical features, imaging modalities, and surgical management were recorded. The primary outcome was 5 year patency. RESULTS: Eighteen patients (25 limbs) underwent surgery. The mean age at the time of surgical procedure was 35 (median 35 years; range 15-49). Presentation was bilateral in seven patients (39%). Diagnosis was made using various imaging modalities, including position stress test, Duplex ultrasonography, computed tomography angiography, magnetic resonance imaging and conventional angiography. In four limbs the popliteal artery was compressed and undamaged (16%), and treatment consisted of musculo-tendinous division alone. In 16 limbs the popliteal artery was damaged with lesions limited to the popliteal artery (64%) where treatment consisted of venous interposition. In five limbs lesions extended beyond the popliteal artery (20%) and procedures included one below knee femoro-popliteal bypass, three femoro-posterior tibial bypasses, and one popliteo-posterior tibial bypass. Musculo-tendinous division was associated with vascular reconstruction in 19 limbs (90%). Mean follow up was 82 months (median 81 months, range 60-120). Five year patency was 84%. CONCLUSION: Long-term outcomes of surgical procedures performed for popliteal artery entrapment syndrome can be considered satisfactory.

Snorkel/chimney and fenestrated endografts for complex abdominal aortic aneurysms.

Complex endovascular aneurysm repair (EVAR) involves extension of the proximal aortic seal zone with preservation of branch vessel patency, thereby expanding the applicability of endografting from the infrarenal to the suprarenal aorta. Snorkel/chimney (Sn-EVAR) and fenestrated EVAR (f-EVAR) serve as the two most commonly utilized advanced endovascular techniques to combat hostile proximal neck anatomy. The purpose of this article is to describe the principles and evolution of these advanced endovascular strategies, technical considerations, and results of sn- and f-EVAR in the management of challenging neck anatomy in abdominal aortic aneurysm disease.

Popliteal artery entrapment syndrome.

Intermittent claudication is frequently encountered in vascular surgical practice in atherosclerotic patients. However, it may also be observed in a younger subset of patients without any cardiovascular risk factors and can represent a challenging diagnosis. Popliteal artery entrapment syndrome is rare but can cause intermittent claudication in young people. There is a lack of consensus about optimal strategies or diagnosis and management, particularly for variants such as functional popliteal entrapment. Since the first description in 1959, knowledge of the pathology and the underlying anatomic abnormalities was advanced through sporadic publications of case reports and small case series, but popliteal artery entrapment syndrome still remains a rare anatomic abnormality. It can be difficult to differentiate from other causes of lower limb pain in young patients, and diagnosis can be challenging. We propose to review clinical symptomatology, classification, radiological diagnosis and treatment of popliteal entrapment syndrome.

Improved efficiency and safety for EVAR with utilization of a hybrid room.

OBJECTIVE: Access to a hybrid endovascular suite is touted as a necessity for advanced endovascular aneurysm repair (EVAR) to improve imaging accuracy and safety. Yet there remain little data documenting this intuitive advantage of a hybrid setup versus a traditional operating room (OR) utilizing a portable fluoroscopic unit (C-arm) for imaging. We hypothesized that standard elective EVAR performed in a hybrid suite would improve procedural efficiency and accuracy, as well minimize patient exposure to both contrast and radiation. METHODS: We retrospectively reviewed a single attending surgeon's EVAR practice, which encompassed the transition to a hybrid endovascular suite (opened July 2010). Only consecutive abdominal aneurysms were included in the analysis to attempt to create a homogenous cohort. All emergent, aorto-uni-iliac (AUI), snorkel, fenestrated, or hybrid procedures were excluded. Standard variables evaluated and compared between the two study subgroups included fluoroscopy time, operative time, contrast use, stent-graft component utilization, complication rates, and short-term endoleaks. RESULTS: From January 2008 to August 2012, we performed 213 EVAR procedures for abdominal aortic aneurysms. After excluding emergent, AUI, snorkel, or hybrid procedures, we analyzed 109 routine EVARs. Fifty-eight consecutive cases were done in the OR with a C-arm until July 2010, and the last 51 cases were done in the hybrid room. Both groups were well matched in terms of demographics, aneurysm morphology, and procedural characteristics. No difference was found in terms of complication rates or operative mortality, although there was a trend towards decreased fluoroscopy time, type I/III endoleaks, and a number of additional endograft components utilized. Compared with patients repaired in the OR/C-arm, EVAR done in the hybrid room resulted in less total OR time and contrast usage (p < .05). CONCLUSIONS: Routine EVAR performed in a hybrid fixed-imaging suite affords greater efficiency and less harmful exposure of contrast and possible radiation to the patient. Accurate imaging quality and deployment is associated with less need for additional endograft components, which should lead to improved cost efficiency. Confirmation of these findings might be necessary in a randomized control trial to fully justify the capital expenditure necessary for hybrid endovascular suites.

EVAR deployment in anatomically challenging necks outside the IFU.

OBJECTIVE: Treatment of abdominal aortic aneurysms with high-risk anatomy (neck length <10-15 mm, neck angle >60°) using commercially available devices has become increasingly common with expanding institutional experience. We examined whether placement of approved devices in short angled necks provides acceptable durability at early and intermediate time points. METHODS: A total of 218 patients (197 men, 21 women) at a single academic center underwent endovascular aneurysm repair (EVAR) with a commercially available device between January 2004 and December 2007. Available medical records, pre- and postoperative imaging, and clinical follow-up were retrospectively reviewed. Patients were divided into those with suitable anatomy (instructions for use, IFU) for EVAR and those with high-risk anatomic aneurysm characteristics (non-IFU). RESULTS: IFU (n = 143) patients underwent repair with Excluder (40%), AneuRx (34%), and Zenith (26%) devices, whereas non-IFU (n = 75) were preferentially treated with Zenith (57%) over Excluder (25%) and AneuRx (17%). Demographics and medical comorbidities between the groups were similar. Operative mortality was 1.4% (2.1% IFU, 0% non-IFU) with mean follow-up of 35 months (range 12-72). Non-IFU patients tended to have larger sac diameters (46.7% ≥60 mm) with shorter (30.7% ≤10 mm), conical (49.3%), and more angled (68% >60°) necks (all p < .05 compared with IFU patients). Operative characteristics revealed that the non-IFU patients were more likely to be treated utilizing suprarenal fixation devices, to require placement of proximal cuffs (13.3% vs. 2.1%, p = .003), and needed increased fluoroscopy time (31 vs. 25 minutes, p = .02). Contrast dose was similar between groups (IFU = 118 mL, non-IFU = 119 mL, p = .95). There were no early or late surgical conversions. Rates of migration, endoleak, need for reintervention, sac regression, and freedom from aneurysm-related death were similar between the groups (p > .05). CONCLUSIONS: EVAR may be performed safely in high-risk patients with unfavorable neck anatomy using particular commercially available endografts. In our experience, the preferential use of active suprarenal fixation and aggressive use of proximal cuffs is associated with optimal results in these settings. Mid-term outcomes are comparable with those achieved in patients with suitable anatomy using a similar range of EVAR devices. Careful and mandatory long-term follow-up will be necessary to confirm the benefit of treating these high-risk anatomic patients.

Cancer survival in Busan, Republic of Korea, 1996-2001.

The Busan cancer registry was established in 1996; cancer registration is done by passive and active methods. The registry contributed survival data for 48 cancer sites or types registered during 1996-2001. Follow-up information has been gleaned predominantly by passive methods with median follow-up ranging between 1-57 months for various cancers. The proportion with histologically verified diagnosis for different cancers ranged between 20-100%; death certificates only (DCOs) comprised 0-53%; 47-100% of total registered cases were included for survival analysis. The top-ranking cancers on 5-year age-standardized relative survival rates were penis (94%), thyroid (91%), non-melanoma skin (89%), placenta (86%), breast (76%), Hodgkin lymphoma (75%) and testis (72%). Five-year relative survival by age group showed a decreasing trend with increasing age groups for cancers of the nasopharynx, gall bladder, lung, bone, soft tissue, breast, cervix, corpus uteri, thyroid, multiple myeloma, lymphoid leukaemia and myeloid leukaemia or was fluctuating for other cancers.

Development of murine leukemia virus-based retroviral vectors with a minimum possibility of cis-activation.

The possibility of insertional mutagenesis in retroviral gene therapy can be reduced by using a vector lacking the enhancer sequence present in the U3 of the long-terminal repeats. However, such vectors suffer from many pitfalls. We attempted to improve a murine leukemia virus-based retroviral vector containing the enhancer-free U3, first by making it easier to construct a producer line and then by introducing the cellular RPL10 promoter as an internal promoter. The reverse orientation of the expression cassette of the transgene was found to give higher transducing titer and higher-level gene expression. The deletion analysis revealed that the 54-bp-long sequence of U3 (34 and 20 bp present at 5' and 3' extreme ends, respectively) was sufficient for the functions of retroviral vectors. The data from the in vitro cell culture assay indicated that the final construct, ROK, containing all these features, had little cis-activation activity, even if it was placed right upstream from the RNA start site of the neighboring gene. Our data suggested that the newly developed vector might provide increased safety, while still producing high viral titer from a stable producer line and high-level gene expression in various target cells including human CD34(+) stem cells.

Evidence for mesenchymal-like sub-populations within squamous cell carcinomas possessing chemoresistance and phenotypic plasticity.

Variable drug responses among malignant cells within individual tumors may represent a barrier to their eradication using chemotherapy. Carcinoma cells expressing mesenchymal markers resist conventional and epidermal growth factor receptor (EGFR)-targeted chemotherapy. In this study, we evaluated whether mesenchymal-like sub-populations within human squamous cell carcinomas (SCCs) with predominantly epithelial features contribute to overall therapy resistance. We identified a mesenchymal-like subset expressing low E-cadherin (Ecad-lo) and high vimentin within the upper aerodigestive tract SCCs. This subset was both isolated from the cell lines and was identified in xenografts and primary clinical specimens. The Ecad-lo subset contained more low-turnover cells, correlating with resistance to the conventional chemotherapeutic paclitaxel in vitro. Epidermal growth factor induced less stimulation of the mitogen-activated protein kinase and phosphatidylinositol-3-kinase pathways in Ecad-lo cells, which was likely due to lower EGFR expression in this subset and correlated with in vivo resistance to the EGFR-targeted antibody, cetuximab. The Ecad-lo and high E-cadherin subsets were dynamic in phenotype, showing the capacity to repopulate each other from single-cell clones. Taken together, these results provide evidence for a low-turnover, mesenchymal-like sub-population in SCCs with diminished EGFR pathway function and intrinsic resistance to conventional and EGFR-targeted chemotherapies.