Diagnostic performance of endoscopic ultrasound-guided tissue acquisition of splenic lesions: systematic review with pooled analysis

Background: Focal splenic lesions are usually incidentally discovered on radiological assessments. Although percutaneous tissue acquisition (TA) under trans-abdominal ultrasound guidance is a well-established technique for obtaining cyto-histological diagnosis of focal splenic lesions, endoscopic ultrasound (EUS)-guided TA has been described in several studies, reporting different safety and outcomes. The aim was to assess the pooled safety, adequacy, and accuracy of EUS-TA of splenic lesions. Methods: A comprehensive review of available evidence was conducted at the end of November 2021. All studies including more than five patients and reporting about the safety, adequacy, and accuracy of EUS-TA of the spleen were included. Results: Six studies (62 patients) were identified; all studies have been conducted using fine-needle aspiration (FNA) needles. Pooled specimen adequacy and accuracy of EUS-TA for spleen characterization were 92.8% [95% confidence interval (CI), 86.3%-99.3%] and 88.2% (95% CI, 79.3%-97.1%), respectively. The pooled incidence of adverse events (six studies, 62 patients) was 4.7% (95% CI, 0.4%-9.7%). Conclusion: EUS-FNA of the spleen is a safe technique with high diagnostic adequacy and accuracy. The EUS-guided approach could be considered a valid alternative to the percutaneous approach for spleen TA

Endoscopic ultrasound fine-needle biopsy vs fine-needle aspiration for lymph nodes tissue acquisition: A systematic review and meta-Analysis

Background: Endoscopic ultrasound (EUS)-guided tissue acquisition represents the choice of methods for suspected lymph nodes (LNs) located next to the gastrointestinal tract. This study aimed to compare the pooled diagnostic performance of EUS-guided fine-needle biopsy (EUS-FNB) and fine-needle aspiration (EUS-FNA) for LNs sampling. Methods: We searched PubMed/MedLine and Embase databases through August 2021. Primary outcome was diagnostic accuracy; secondary outcomes were sensitivity, specificity, sample adequacy, optimal histological core procurement, number of passes, and adverse events. We performed a pairwise meta-Analysis using a random-effects model. The results are presented as odds ratio (OR) or mean difference along with 95% confidence interval (CI). Results: We identified nine studies (1,276 patients) in this meta-Analysis. Among these patients, 66.4% were male; the median age was 67 years. Diagnostic accuracy was not significantly different between the two approaches (OR, 1.31; 95% CI, 0.81-2.10; P = 0.270). The accuracy of EUS-FNB was significantly higher when being performed with newer end-cutting needles (OR, 1.87; 95% CI, 1.17-3.00; P = 0.009) and in abdominal LNs (OR, 2.48; 95% CI, 1.52-4.05; P < 0.001) than that of EUS-FNA. No difference in terms of sample adequacy was observed between the two approaches (OR, 1.40; 95% CI, 0.46-4.26; P = 0.550); however, histological core procurement and diagnostic sensitivity with EUS-FNB were significantly higher than those with EUS-FNA (OR, 6.15; 95% CI, 1.51-25.07; P = 0.010 and OR, 1.87; 95% CI, 1.27-2.74, P = 0.001). The number of needle passes needed was significantly lower in the EUS-FNB group than in the EUS-FNA group (mean difference,-0.54; 95% CI,-0.97 to-0.12; P = 0.010). Conclusions: EUS-FNA and EUS-FNB perform similarly in LN sampling; however, FNB performed with end-cutting needles outperformed FNA in terms of diagnostic accuracy

Methods for Drainage of Distal Malignant Biliary Obstruction after ERCP Failure: A Systematic Review and Network Meta‐Analysis

There is scarce evidence on the comparison between different methods for the drainage of distal malignant biliary obstruction (DMBO) after endoscopic retrograde cholangiopancreatography (ERCP) failure. Therefore, we performed a network meta‐analysis to compare the outcomes of these techniques. We searched main databases through September 2021 and identified five randomized controlled trials. The primary outcome was clinical success. The secondary outcomes were technical success, overall and serious adverse event rate. Percutaneous trans‐hepatic biliary drainage was found to be inferior to other interventions (PTBD: RR 1.01, 0.88– 1.17 with EUS‐choledochoduodenostomy (EUS‐CD); RR 1.03, 0.86–1.22 with EUS-hepaticogastrostomy (EUS‐HG); RR 1.42, 0.90–2.24 with surgical hepaticojejunostomy). The comparison between EUS‐HG and EUS‐CD was not significant (RR 1.01, 0.87–1.17). Surgery was not superior to other interventions (RR 1.40, 0.91–2.13 with EUS‐CD and RR 1.38, 0.88–2.16 with EUS‐HG). No difference in any of the comparisons concerning adverse event rate was detected, although PTBD showed a slightly poorer performance on ranking analysis (SUCRA score 0.13). In conclusion, all interventions seem to be effective for the drainage of DMBO, although PTBD showed a trend towards higher rates of adverse events

Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer

Risk assessment and treatment choice remain a challenge in early non-small-cell lung cancer (NSCLC). Alternative splicing is an emerging source for diagnostic, prognostic and therapeutic tools. Here, we investigated the prognostic value of the actin cytoskeleton regulator hMENA and its isoforms, hMENA(11a) and hMENA Delta v6, in early NSCLC. The epithelial hMENA(11a) isoform was expressed in NSCLC lines expressing E-CADHERIN and was alternatively expressed with hMENA Delta v6. Enforced expression of hMENA Delta v6 or hMENA(11a) increased or decreased the invasive ability of A549 cells, respectively. hMENA isoform expression was evaluated in 248 node-negative NSCLC. High pan-hMENA and low hMENA(11a) were the only independent predictors of shorter disease-free and cancer-specific survival, and low hMENA(11a) was an independent predictor of shorter overall survival, at multivariate analysis. Patients with low pan-hMENA/high hMENA(11a) expression fared significantly better (P <= 0.0015) than any other subgroup. Such hybrid variable was incorporated with T-size and number of resected lymph nodes into a 3-class-risk stratification model, which strikingly discriminated between different risks of relapse, cancer-related death, and death. The model was externally validated in an independent dataset of 133 patients. Relative expression of hMENA splice isoforms is a powerful prognostic factor in early NSCLC, complementing clinical parameters to accurately predict individual patient risk

Services as a New Engine of Growth for ASEAN, the People’s Republic of China, and India

An increasing services orientation is likely to be a key feature of the economies of the Association of Southeast Asian Nations (ASEAN), the People's Republic of China, and India (collectively referred to as "ACI") over the medium-term. This paper aims to present a compendium of relevant data on the state of the services sector in the ACI countries, focusing on its contribution to overall economic activity, employment, and growth. To do this, it relies heavily on standard international sources, as well as national statistics in some cases. It also examines to the extent possible - given data restrictions - the services policy environment in the ACI countries, focusing on its implications for regional and international integration of services markets

Trade openness, real exchange rates and job reallocation

This paper investigates the impact of real exchange rate movements on job reallocation at the industry level. The analysis focuses on the manufacturing sector of Belgium, using data for 82 NACE 3-digit industries, over the time span 1996-2002. I find that real exchange rate changes do have a significant impact on job flows, and that this impact is magnified by increasing levels of trade exposure. In particular, a real appreciation is found to lower net employment growth through higher job destruction, while job creation is not significantly affected. These results are in line with previous empirical evidence on the United States, and differ from earlier findings for France and Germany, where the adjustment to real exchange rate shocks has been found to occur mainly through the job creation margin. I suggest that these differences may be explained by the fact that Belgium is a small open economy

Recessive nephrocerebellar syndrome on the Galloway-Mowat syndrome spectrum is caused by homozygous protein-truncating mutations of WDR73.

We describe a novel nephrocerebellar syndrome on the Galloway-Mowat syndrome spectrum among 30 children (ages 1.0 to 28 years) from diverse Amish demes. Children with nephrocerebellar syndrome had progressive microcephaly, visual impairment, stagnant psychomotor development, abnormal extrapyramidal movements and nephrosis. Fourteen died between ages 2.7 and 28 years, typically from renal failure. Post-mortem studies revealed (i) micrencephaly without polymicrogyria or heterotopia; (ii) atrophic cerebellar hemispheres with stunted folia, profound granule cell depletion, Bergmann gliosis, and signs of Purkinje cell deafferentation; (iii) selective striatal cholinergic interneuron loss; and (iv) optic atrophy with delamination of the lateral geniculate nuclei. Renal tissue showed focal and segmental glomerulosclerosis and extensive effacement and microvillus transformation of podocyte foot processes. Nephrocerebellar syndrome mapped to 700 kb on chromosome 15, which contained a single novel homozygous frameshift variant (WDR73 c.888delT; p.Phe296Leufs*26). WDR73 protein is expressed in human cerebral cortex, hippocampus, and cultured embryonic kidney cells. It is concentrated at mitotic microtubules and interacts with α-, β-, and γ-tubulin, heat shock proteins 70 and 90 (HSP-70; HSP-90), and the carbamoyl phosphate synthetase 2/aspartate transcarbamylase/dihydroorotase multi-enzyme complex. Recombinant WDR73 p.Phe296Leufs*26 and p.Arg256Profs*18 proteins are truncated, unstable, and show increased interaction with α- and β-tubulin and HSP-70/HSP-90. Fibroblasts from patients homozygous for WDR73 p.Phe296Leufs*26 proliferate poorly in primary culture and senesce early. Our data suggest that in humans, WDR73 interacts with mitotic microtubules to regulate cell cycle progression, proliferation and survival in brain and kidney. We extend the Galloway-Mowat syndrome spectrum with the first description of diencephalic and striatal neuropathology

Reliable quantification of the potential for equations based on spot urine samples to estimate population salt intake: protocol for a systematic review and meta-analysis.

BACKGROUND: Methods based on spot urine samples (a single sample at one time-point) have been identified as a possible alternative approach to 24-hour urine samples for determining mean population salt intake. OBJECTIVE: The aim of this study is to identify a reliable method for estimating mean population salt intake from spot urine samples. This will be done by comparing the performance of existing equations against one other and against estimates derived from 24-hour urine samples. The effects of factors such as ethnicity, sex, age, body mass index, antihypertensive drug use, health status, and timing of spot urine collection will be explored. The capacity of spot urine samples to measure change in salt intake over time will also be determined. Finally, we aim to develop a novel equation (or equations) that performs better than existing equations to estimate mean population salt intake. METHODS: A systematic review and meta-analysis of individual participant data will be conducted. A search has been conducted to identify human studies that report salt (or sodium) excretion based upon 24-hour urine samples and spot urine samples. There were no restrictions on language, study sample size, or characteristics of the study population. MEDLINE via OvidSP (1946-present), Premedline via OvidSP, EMBASE, Global Health via OvidSP (1910-present), and the Cochrane Library were searched, and two reviewers identified eligible studies. The authors of these studies will be invited to contribute data according to a standard format. Individual participant records will be compiled and a series of analyses will be completed to: (1) compare existing equations for estimating 24-hour salt intake from spot urine samples with 24-hour urine samples, and assess the degree of bias according to key demographic and clinical characteristics; (2) assess the reliability of using spot urine samples to measure population changes in salt intake overtime; and (3) develop a novel equation that performs better than existing equations to estimate mean population salt intake. RESULTS: The search strategy identified 538 records; 100 records were obtained for review in full text and 73 have been confirmed as eligible. In addition, 68 abstracts were identified, some of which may contain data eligible for inclusion. Individual participant data will be requested from the authors of eligible studies. CONCLUSIONS: Many equations for estimating salt intake from spot urine samples have been developed and validated, although most have been studied in very specific settings. This meta-analysis of individual participant data will enable a much broader understanding of the capacity for spot urine samples to estimate population salt intake

Phase II study of gemcitabine and vindesine in patients with previously untreated non-resectable non-small-cell lung cancer

Because both vindesine and gemcitabine are active drugs in advanced non-small-cell lung cancer (NSCLC), with different modes of action and only partly overlapping toxicity, a phase II study was performed. Gemcitabine 1000 mg m−2 was given on days 1, 8 and 15 every 4 weeks, while vindesine 3 mg m−2 was administered weekly for 7 weeks, then every 2 weeks. A total of 42 patients with nonresectable NSCLC were included. The median age of patients was 56 years; 57% were men, 52% had adenocarcinoma, 31% squamous cell carcinoma and 17% had large-cell carcinoma. The performance status ranged from 0 to 2 with 83% in performance status 1. The majority (55%) had stage IV disease, while 40% had stage III B and 5% stage III A disease. WHO grade 3–4 leucopenia occurred in five patients (12%) and 9% had grade 4 neutropenia. Thrombocytopenia grade 3–4 was observed in six patients (15%). There were no septic death or bleeding episodes. One patient had a transient WHO grade 4 increase in bilirubin, and four patients had a decrease in glomerular filtration rate below the normal limit; one of these patients developed a non-reversible renal insufficiency. Ten patients (24%) complained of dyspnoea of uncertain mechanism, possibly involving bronchoconstriction. There were one complete and seven partial responses among 40 assessable patients (20%, 95% confidence limits 9–36%). Median response duration was 31 weeks (range 11–83 weeks) and median survival time 31 weeks (range 2–171 weeks). The current combination of gemcitabine and vindesine does not appear to be promising for further examination because of the toxicity and somewhat disappointing activity. © 1999 Cancer Research Campaig

The Acceptability of Internet-Based Treatment and Characteristics of an Adult Sample with Obsessive Compulsive Disorder: An Internet Survey

Background: Obsessive-compulsive disorder (OCD) is a disabling anxiety disorder, but most individuals delay seeking treatment. Internet-based cognitive behavioural therapy (iCBT) is an innovative service delivery method that may help to improve access to care, but the acceptability to consumers of such programs has not yet been established. Methodology: People with symptoms of OCD were invited to complete an online survey enquiring about demographic characteristics, symptom severity, and acceptability of Internet-based treatment. Demographic and symptom severity data were compared with people with OCD identified in a national epidemiological survey and with a sample of patients with OCD from a specialist outpatient anxiety clinic. Participants: 129 volunteers to an online Internet survey, 135 patients at a specialist anxiety disorders outpatient clinic, and 297 cases identified in a national epidemiological survey. Main Measures: Demographic characteristics, and severity of symptoms as measured by the Kessler 10-Item scale, the 12-item World Health Organisation Disability Assessment Schedule - Second Edition and the Yale Brown Obsessive Compulsive Scale - Self Report Version. Principal Findings: The Internet sample was similar demographically but reported more severe symptoms than the comparison groups, although had similar severity of symptoms of OCD compared with other clinical samples reported in the literature. Participants reported Internet-based treatment for OCD would be highly acceptable. Conclusions: Internet-based treatment may reduce barriers to accessing treatment to people with OCD. Individuals in this study were similar demographically to other samples and had similar severity of symptoms as those identified in other clinical samples, suggesting that Internet-based treatment using techniques employed in face-to-face treatment may be effective in this group. Internet-based treatments for OCD need to be developed and evaluated