Non-esophageal eosinophilic gastrointestinal diseases: a narrative review.

Eosinophilic gastrointestinal disorders are a group of rare diseases characterized by the infiltration of eosinophils in the gastrointestinal wall in a greater amount than in homeostatic conditions. 'Non-esophageal eosinophilic gastrointestinal disorders' is the umbrella term for all eosinophilic gastrointestinal disorders outside of the well known eosinophilic esophagitis. This includes eosinophilic gastritis, eosinophilic enteritis and eosinophilic colitis. The clinical presentation is atypical and not very different for the three disorders. The depth of infiltration has a bigger influence on the presenting symptoms than the disease location. Although the frequency of diagnosis and research in this subject is increasing over time, non-esophageal eosinophilic disorders are rare and high quality evidence is limited to date. In this narrative review, we provide an overview of the latest insights in the pathophysiology, diagnostic approach and available treatment options. Transcriptome studies have found the pathogenesis to be T helper type 2 driven. Various laboratory findings can be used to trigger raised suspicion and investigation with endoscopy. As the endoscopic appearance of the mucosa is normal in most cases, multiple biopsies in each segment are needed to quantify the amount of eosinophils in the tissue. Eosinophilic cut-offs for diagnosis are a controversial topic and a consensus is still lacking. A recently developed tissue based diagnostic platform which measures differentially expressed genes might be available in the future to classify patients with intermediate eosinophilic tissue levels under the cut-off. For the treatment, corticosteroids are still the cornerstone of treatment but promising research suggests a role of biologicals, such as Lirentelimab (anti-siglec 8) in particular.

Myocardial deformation imaging by 2D speckle tracking echocardiography for assessment of diastolic dysfunction in murine cardiopathology.

Diastolic dysfunction is increasingly identified as a key, early onset subclinical condition characterizing cardiopathologies of rising prevalence, including diabetic heart disease and heart failure with preserved ejection fraction (HFpEF). Diastolic dysfunction characterization has important prognostic value in management of disease outcomes. Validated tools for in vivo monitoring of diastolic function in rodent models of diabetes are required for progress in pre-clinical cardiology studies. 2D speckle tracking echocardiography has emerged as a powerful tool for evaluating cardiac wall deformation throughout the cardiac cycle. The aim of this study was to examine the applicability of 2D speckle tracking echocardiography for comprehensive global and regional assessment of diastolic function in a pre-clinical murine model of cardio-metabolic disease. Type 2 diabetes (T2D) was induced in C57Bl/6 male mice using a high fat high sugar dietary intervention for 20 weeks. Significant impairment in left ventricle peak diastolic strain rate was evident in longitudinal, radial and circumferential planes in T2D mice. Peak diastolic velocity was similarly impaired in the longitudinal and radial planes. Regional analysis of longitudinal peak diastolic strain rate revealed that the anterior free left ventricular wall is particularly susceptible to T2D-induced diastolic dysfunction. These findings provide a significant advance on characterization of diastolic dysfunction in a pre-clinical mouse model of cardiopathology and offer a comprehensive suite of benchmark values for future pre-clinical cardiology studies.

A single-centre analysis of post-colonoscopy colorectal cancer.

PATIENTS AND METHODS: A prospective registration of patients with colorectal cancer and a colonoscopy within the last 10 years. We tried to classify these post-colonoscopy colorectal cancers (PCCRCs) by most reasonable explanation and into subcategories suggested by the World Endoscopy Organization (WEO) and calculated the unadjusted PCCRC rate. RESULTS: 47 PCCRCs were identified. The average age at diagnosis of PCCRC was 73 years. PCCRCs were more located in the right colon with a higher percentage of MSI-positive and B-RAF mutated tumours. The average period between index colonoscopy and diagnosis of PCCRC was 4.2 years. Sixty-eight % of all PCCRCs could be explained by procedural factors. The mean PCCRC-3y of our department was 2.46%. CONCLUSIONS: The data of our centre are in line with the data of the literature from which can be concluded that most postcolonoscopy colorectal cancers are preventable. The PCCRC-3y is an important quality measure for screening colonoscopy. Ideally all centres involved in the population screening should measure the PCCRC-3 y annually, with cooperation of the cancer registry and reimbursement data provided by the Intermutualistic Agency (IMA).

Current practice in approaching controversial diagnostic and therapeutic topics in gastroenteropancreatic neuroendocrine neoplasm management. Belgian multidisciplinary expert discussion based on a modified Delphi method.

BACKGROUND AND STUDY AIMS: Neuroendocrine neoplasms (NENs) are relatively rare, with marked clinical and biological heterogeneity. Consequently, many controversial areas remain in diagnosis and optimal treatment stratification for NEN patients. We wanted to describe current clinical practice regarding controversial NEN topics and stimulate critical thinking and mutual learning among a Belgian multidisciplinary expert panel. PATIENTS AND METHODS: A 3-round, Delphi method based project, coordinated by a steering committee (SC), was applied to a predefined multidisciplinary NEN expert panel studying the following controversial topics : factors guiding therapeutic decision making, the use of somatostatin analogues (SSA) in adjuvant setting, the interference between non-radioactive and radioactive SSAs, challenging small intestine neuroendocrine tumor (NET) cases, the approach of the carcinoid syndrome, the role of chemotherapy in well differentiated NET, the relevance of NET G3 and neuroendocrine carcinoma subclassification and the role of imaging techniques in NEN management. RESULTS: A high level of consensus exists regarding the necessary diagnostic work-up, use of imaging techniques and interference between non-radioactive and radioactive SSAs. However, the prognostic impact of tumor functionality might be overrated and adequate diarrhea differential diagnostic work-up in these patients is underused. Significant differences are seen between individual experts and centers regarding treatment preferences both on the treatment modality level, as well as the choice of specific drugs (e.g. chemotherapy regimen). CONCLUSIONS: A Delphi-like multi-round expert discussion proves useful to boost critical thinking and discussion among experts of different background, as well as to describe current clinical practice and stimulate mutual learning in the absence of high-level scientific guidance.

Accuracy of comprehensive PCR analysis of nasopharyngeal and oropharyngeal swabs for CT-scan-confirmed pneumonia in elderly patients: a prospective cohort study.

OBJECTIVES: We aimed to assess the accuracy of PCR detection of viruses and bacteria on nasopharyngeal and oropharyngeal swabs (NPS) for the diagnosis of pneumonia in elderly individuals. METHODS: We included consecutive hospitalized elderly individuals suspected of having pneumonia. At inclusion, NPS were collected from all participants and tested by PCR for the presence of viral and bacterial respiratory pathogens (index test, defined as comprehensive molecular testing). Routine diagnostic tests (blood and sputum culture, urine antigen detection) were also performed. The reference standard was the presence of pneumonia on a low-dose CT scan as assessed by two independent expert radiologists. RESULTS: The diagnosis of pneumonia was confirmed in 127 of 199 (64%) included patients (mean age 83 years, community-acquired pneumonia in 105 (83%)). A pathogen was identified by comprehensive molecular testing in 114 patients (57%) and by routine methods in 22 (11%). Comprehensive molecular testing was positive for viruses in 62 patients (31%) and for bacteria in 73 (37%). The sensitivity and specificity were 61% (95% CI 53%-69%) and 50% (95% CI 39%-61%) for comprehensive molecular testing, and 14% (95% CI 82%-21%) and 94% (95% CI 86%-98%) for routine testing, respectively. Positive likelihood ratio was 2.55 for routine methods and 1.23 for comprehensive molecular testing. CONCLUSION: Comprehensive molecular testing of NPS increases the number of pathogens detected compared with routine methods, but results are poorly predictive of the presence of pneumonia. Hence, comprehensive molecular testing is unlikely to impact clinical decision-making (NCT02467192). CLINICAL TRIALS REGISTRATION: NCT02467192.

Development of Precision Small-Molecule Proneurotrophic Therapies for Neurodegenerative Diseases.

Age-related neurodegenerative diseases, such as Alzheimer's disease, will represent one of the largest future burdens on worldwide healthcare systems due to the increasing proportion of elderly in our society. As deficiencies in neurotrophins are implicated in the pathogenesis of many age-related neurodegenerative disorders, it is reasonable to consider that global neurotrophin resistance may also become a major healthcare threat. Central nervous system networks are effectively maintained through aging by neuroprotective and neuroplasticity signaling mechanisms which are predominantly controlled by neurotrophin receptor signaling. Neurotrophin receptors are single pass receptor tyrosine kinases that form dimeric structures upon ligand binding to initiate cellular signaling events that control many protective and plasticity-related pathways. Declining functionality of the neurotrophin ligand-receptor system is considered one of the hallmarks of neuropathological aging. Therefore, it is imperative to develop effective therapeutic strategies to contend with this significant issue. While the therapeutic applications of cognate ligands for neurotrophin receptors are limited, the development of nonpeptidergic, small-molecule ligands can overcome these limitations, and productively regulate this important receptor system with beneficial effects. Using our advanced knowledge of the high-dimensionality complexity of receptor systems, the future generation of precision medicines targeting these systems will be an attainable goal.

[Limitations of active therapeutic and palliative care in chronic respiratory disease]. / Intensité des soins lors des exacerbations et des complications des pathologies respiratoires chroniques.

The issue of intensive and palliative care in patients with chronic disease frequently arises. This review aims to describe the prognostic factors of chronic respiratory diseases in stable and in acute situations in order to improve the management of these complex situations. The various laws on patients' rights provide a legal framework and define the concept of unreasonable obstinacy. For patients with chronic obstructive pulmonary disease, the most robust decision factors are good knowledge of the respiratory disease, the comorbidities, the history of previous exacerbations and patient preferences. In the case of idiopathic pulmonary fibrosis, it is necessary to know if there is a prospect of transplantation and to assess the reversibility of the respiratory distress. In the case of amyotrophic lateral sclerosis, treatment decisions depend on the presence of advance directives about the use of intubation and tracheostomy. For lung cancer patients, general condition, cancer history and the tumor treatment plan are important factors. A multidisciplinary discussion that takes into account the patient's medical history, wishes and the current state of knowledge permits the taking of a coherent decision.

[Noninvasive ventilation. The 2015 guidelines from the Groupe Assistance Ventilatoire (GAV) of the Société de Pneumologie de Langue Française (SPLF)]. / Ventilation non invasive. Les conseils 2015 du Groupe assistance ventilatoire (GAV) de la Société de pneumologie de langue française (SPLF).

A task force issued from the Groupe Assistance Ventilatoire (GAV) of the Société de Pneumologie de Langue Française (SPLF) was committed to develop a series of expert advice concerning various practical topics related to long-term non invasive ventilation by applying the Choosing Wisely® methodology. Three topics were selected: monitoring of noninvasive ventilation, the interpretation of data obtained from built-in devices coupled to home ventilators and the role of hybrid modes (target volume with variable pressure support. For each topic, the experts have developed practical tips based on a comprehensive analysis of recent insights and evidence from the literature and from clinical experience.

Medium-term cost-effectiveness of an automated non-invasive ventilation outpatient set-up versus a standard fixed level non-invasive ventilation inpatient set-up in obese patients with chronic respiratory failure: a protocol description.

INTRODUCTION: Obesity is an escalating issue, with an accompanying increase in referrals of patients with obesity-related respiratory failure. Currently, these patients are electively admitted to hospital for initiation of non-invasive ventilation (NIV), but it is unknown whether outpatient initiation is as effective as inpatient set-up. We hypothesise that outpatient set-up using an autotitrating NIV device will be more cost-effective than a nurse-led inpatient titration and set-up. METHODS AND ANALYSIS: We will undertake a multinational, multicentre randomised controlled trial. Participants will be randomised to receive the usual inpatient set-up, which will include nurse-led initiation of NIV or outpatient set-up with an automated NIV device. They will be stratified according to the trial site, gender and previous use of NIV or continuous positive airway pressure. Assuming a 10% dropout rate, a total sample of 82 patients will be required. Cost-effectiveness will be evaluated using standard treatment costs and health service utilisation as well as health-related quality of life measures (severe respiratory insufficiency (SRI) and EuroQol-5 dimensions (EQ-5D)). A change in the SRI questionnaire will be based on the analysis of covariance adjusting for the baseline measurements between the two arms of patients. ETHICS AND DISSEMINATION: This study has been approved by the Westminster National Research Ethics Committee (11/LO/0414) and is the trial registered on the UKCRN portfolio. The trial is planned to start in January 2015 with publication of the trial results in 2017. TRIAL REGISTRATION NUMBER: ISRCTN 51420481.

Gait abnormalities in obstructive sleep apnea and impact of continuous positive airway pressure.

We aimed to determine the effect of continuous positive airway pressure (CPAP) on gait in obstructive sleep apnea (OSA) patients. Gait during single and dual tasks was recorded in 15 OSA patients at baseline and after 8 weeks of CPAP therapy. Step and stance time improved after CPAP. We showed a specific dual-task effect in the condition of verbal fluency. Eight weeks of CPAP seems to improve gait of OSA patients that are specifically disturbed by the dual task of verbal fluency.

[Proposal for a systematic analysis of polygraphy or polysomnography for identifying and scoring abnormal events occurring during non-invasive ventilation]. / Proposition pour une analyse systématique de la polygraphie et de la polysomnographie afin d'identifier les évènements anormaux survenant pendant la ventilation non invasive.

Non-invasive ventilation (NIV) is recognised as an effective treatment for chronic hypercapnic respiratory failure. Monitoring NIV during sleep may be preferable to daytime assessment. This paper reports the findings of an international consensus group, which systematically analysed nocturnal polygraphic or polysomnographic tracings recorded with either volume-cycled or pressure-cycled ventilators. A systematic description of nocturnal respiratory events, which occur during NIV, is proposed: leaks, obstruction at different levels of the upper airway (glottis and/or pharynx), with or without decrease of respiratory drive and asynchrony.

[Nocturnal monitoring of home non-invasive ventilation: Contribution of simple tools such as pulse-oximetry, capnography, built-in ventilator software and autonomic markers of sleep fragmentation]. / Monitorage nocturne de la ventilation non invasive à domicile : l'apport d'outils simples tels que l'oxymétrie de pouls, la capnographie, les logiciels intégrés des ventilateurs et les marqueurs autonomiques de fragmentation du sommeil.

Complex respiratory events, which may have a detrimental effect on both quality of sleep and control of nocturnal hypoventilation, occur during sleep in patients treated by non-invasive ventilation (NIV). Among these events are patient-ventilator asynchrony, increases in upper airway resistance with or without increased respiratory drive, and leaks. Detection of these events is important in order to select the most appropriate ventilator settings and interface. Simple tools can provide important information when monitoring NIV. Pulse-oximetry is important to ensure that an adequate SpO2 is provided, and to detect either prolonged or short and recurrent desaturations. However, the specificity of pulse-oximetry tracings under NIV is low. Transcutaneous capnography discriminates between hypoxemia related to V/Q mismatch and hypoventilation, documents correction of nocturnal hypoventilation, and may detect ventilator-induced hyperventilation, a possible cause for central apnea/hypopnea and glottic closure. Data provided by ventilator software helps the clinician by estimating ventilation, tidal volume, leaks, rate of inspiratory or expiratory triggering by the patient, although further validation of these signals by independent studies is indicated. Finally, autonomic markers of sympathetic tone using signals such as pulse wave amplitude of the pulse-oximetry signal can provide reliable information of sleep fragmentation.

Ultra-late recurrences of gastro-intestinal carcinoma after primary resection: the mechanism of dormancy.

Curative resection of limited gastro-intestinal carcinoma does not always mean curation with tumor-free long-term survival. We present two cases of ultra-late recurrence 14 years after initial treatment. In the first case a 50-year-old male underwent in 1997 a subtotal esophagectomy with tubulation of the stomach for a localized Barrett carcinoma. Postoperative staging showed a poorly differentiated adenocarcinoma, pT1N1 (stage IIB). In May 2011, 14 years after the initial resection, multiple bone metastases were diagnosed and a biopsy confirmed the poorly differentiated carcinoma with the same characteristics as the primary tumor. Investigations showed no evidence for a new primary tumor. The second case is a 52-year old man who underwent a low anterior resection for a small rectal cancer in 1997, histologically a well differentiated adenocarcinoma, stage IB (pT2NO). In December 2011 multiple metastases were diagnosed and a biopsy showed a metastasis from a mucinous carcinoma, suggestive for a colorectal carcinoma. There was also no evidence for a new primary tumor. Although the prognosis of limited esophageal and colorectal cancer is good, recurrence is always possible and an ultra-late recurrence may exceptionally occur. The mechanism of tumor dormancy is described.

Influence of nitric oxide synthase inhibition on the motility and sensitivity of distal colon in man.

BACKGROUND: Alterations of nitrergic innervation have been implicated in the pathophysiology of motor-sensory abnormalities of post infectious functional dyspepsia and could be involved in the pathophysiology of post infectious irritable bowel syndrome. The role of nitrergic neurons in the control of distal colonic sensorimotor function in man is not known. The aim of this study is to evaluate the motility and sensitivity of distal colon in healthy subjects before and after a nitric oxide synthase inhibitor (L-NMMA). METHODS: A 700-mL balloon connected with a barostat-manometry assembly was placed in the descending colon of 10 healthy subjects and distension (4 mmHg/2 min) was performed. Intra-balloon pressure was then set at minimal distending pressure + 2 mmHg for 30 min, placebo or L-NMMA (8 mg kg(-1) h(-1)) was administered i.v. in double-blind, randomized, cross-over design and distensions were repeated. KEY RESULTS: Placebo and L-NMMA did not influence colonic compliance, motility index, and tone. Placebo did not affect thresholds for first perception and discomfort and the areas under the pressure-perception curve. L-NMMA did not alter thresholds for first perception, but significantly decreased the pressure thresholds for discomfort (P = 0.008) and increased the areas under the pressure-perception score (P = 0.01). CONCLUSIONS & INFERENCES: In man, inhibition of nitric oxide synthase sensitizes the distal colon to distension. Impaired nitrergic innervation is a mechanism that may be involved in the pathogenesis of hypersensitivity to colonic distension.

[Systemic and oropharyngeal side effects of inhaled corticosteroids]. / Effets secondaires systémiques et oropharyngés des corticostéroïdes inhalés.

The use of inhaled corticosteroids (ICS) is an important component of asthma management. Although their main impact is on airway inflammation, ICS are not devoid of systemic side effects (adrenal insufficiency, osteoporosis, brittle skin, ocular effects, growth retardation). Oropharyngeal side effects are also reported. These effects appear dose and duration dependent. They also vary according to the type of ICS used, its method of administration and drug interactions. It is recommended to titrate ICS to the lowest effective dose, to regularly reconsider their indication and to be aware of drug interactions. In addition, a change in ICS may have a favorable impact on side effects.

[Chronic obstructive pulmonary disease: risk and benefit of testosterone therapy]. / Bronchopneumopathie chronique obstructive: risques et bénéfices d'un traitement de testostérone.

Muscular wasting is frequently encountered in COPD patients and is related to a decrease in exercise tolerance, a higher morbidity and mortality. One of the potential causes isa low serum testosterone, which is frequent in COPD. Various studies have explored the effect of testosterone administration alone or as part of combined pulmonary rehabilitation and nutrition protocols. Testosterone had a positive impact on muscle mass and force, and to a lesser extent on physical endurance and respiratory parameters. Future studies should better define appropriate dosage and treatment duration. In the meantime, testosterone should be administered to COPD patients with overt hypogonadism, or in multidisciplinary specialized programmes.

Dysphagia lusoria caused by a right-sided aorta.

We report a case of an 80-year-old female with dysphagia lusoria caused by oesophageal compression by a right-sided atheromatous aorta. The relationship between aortic root vascular anomalies and dysphagia has been clearly established in literature and can be diagnosed by a barium swallowing study, followed by CT or MRI. Aortic anomalies and variations in aortic branches are caused by embryonic malformations and are mostly described in association with congenital heart lesions. In this pauci-symptomatic patient, the preferred treatment is a conservative management.

Immune response and immunotherapy in intraepithelial and invasive lesions of the uterine cervix.

Infection with the human papillomavirus virus (HPV) induces innate and acquired immune responses in the cervical stroma, which are a delicate, balanced and generally unpredictable immunological defense. Because of the immunological breaks that the HPV virus causes, eradication of infected cells does not occur, potentially leading to development of intraepithelial and invasive lesions. Advances in our understanding of the immune system and in the definition of antigens in tumor cells has led to many new treatment strategies. As a result, immunotherapy has the potential to be the most specific treatment for tumors, and one that requires elaboration. Recently, immunotherapy with interferon and dendritc cells has been used on intrapepithelial and invasive cervical lesions with promising results.