Growth differentiation factor 15 (GDF15) and semaglutide inhibit food intake and body weight through largely distinct, additive mechanisms.

AIMS: To evaluate whether the potent hypophagic and weight-suppressive effects of growth differentiation factor-15 (GDF15) and semaglutide combined would be a more efficacious antiobesity treatment than either treatment alone by examining whether the neural and behavioural mechanisms contributing to their anorectic effects were common or disparate. MATERIALS/METHODS: Three mechanisms were investigated to determine how GDF15 and semaglutide induce anorexia: the potentiation of the intake suppression by gastrointestinal satiation signals; the reduction in motivation to feed; and the induction of visceral malaise. We then compared the effects of short-term, combined GDF15 and semaglutide treatment on weight loss to the individual treatments. Rat pharmaco-behavioural experiments assessed whether GDF15 or semaglutide added to the satiating effects of orally gavaged food and exogenous cholecystokinin (CCK). A progressive ratio operant paradigm was used to examine whether GDF15 or semaglutide reduced feeding motivation. Pica behaviour (ie, kaolin intake) and conditioned affective food aversion testing were used to evaluate visceral malaise. Additionally, fibre photometry studies were conducted in agouti-related protein (AgRP)-Cre mice to examine whether GDF15 or semaglutide, alone or in combination with CCK, modulate calcium signalling in hypothalamic AgRP neurons. RESULTS: Semaglutide reduced food intake by amplifying the feeding-inhibitory effect of CCK or ingested food, inhibited the activity of AgRP neurons when combined with CCK, reduced feeding motivation and induced malaise. GDF15 induced visceral malaise but, strikingly, did not affect feeding motivation, the satiating effect of ingested food or CCK signal processing. Combined GDF15 and semaglutide treatment produced greater food intake and body weight suppression than did either treatment alone, without enhancing malaise. CONCLUSIONS: GDF15 and semaglutide reduce food intake and body weight through largely distinct processes that produce greater weight loss and feeding suppression when combined.

The Role of Endobronchial Ultrasound in Early-Stage Non-Small Cell Lung Cancer.

Aim The aim of this study is to assess the impact of EBUS on the concordance of clinical and pathological NSCLC staging in our center. Methods Data was collected retrospectively from the hospital database regarding patients who underwent surgical resection for early stage NSCLC between 2012 and 2017. Results A total of 251 patients were included. The mean age was 67 (±9), 55% (n=137) were male and 83% (n=209) were current/former smokers. In group A (n=154, 61%) clinical nodal stage (cN) was established from a combination of CT, PET CT and mediastinoscopy. Group B underwent additional EBUS (n=97, 39%). cN and pathological nodal staging (pN) were concordant in 78% (n=120) in group A versus 62% (n=60) in group B (p=0.009). Conclusion This study demonstrated higher rates of nodal discordance in patients who underwent EBUS which contrasts existing data that demonstrates improved concordance with EBUS. We describe these findings and potential explanations further in this study.

Safety of percutaneous renal cryoablation: an international multicentre experience from the EuRECA retrospective percutaneous database.

OBJECTIVE: To investigate the safety profile of percutaneous cryoablation of renal tumours < 7 cm, utilising data extracted from an international multicentre registry. MATERIALS AND METHODS: A retrospective review of all immediate and delayed complications from a multicentre database was performed and was categorised according to the Clavien-Dindo classification. Statistical analysis was performed for both overall complications (all Clavien-Dindo) and major complications (Clavien-Dindo 3 to 5). The following criteria were identified as potential predictive factors for complications: centre number, modality of image guidance, tumour size (≤ 4 cm vs. > 4 cm), number of tumours treated in the same session (1 vs. > 1) and tumour histology. RESULTS: A total of 713 renal tumours underwent ablation in 647 individual sessions. In 596 of the cases, one tumour was treated; in the remaining 51 cases, several tumours were treated per session. Mean lesion size was 2.8 cm. Fifty-four complications (Clavien-Dindo 1 to 5) occurred as a result of the 647 procedures, corresponding to an overall complication rate of 8.3%. The most frequent complication was bleeding (3.2%), with 9 cases (1.4%) requiring subsequent treatment. The rate of major complication was 3.4%. The only statistically significant prognostic factor for a major complication was a tumour size > 4 cm. CONCLUSION: Percutaneous renal cryoablation is associated with a low rate of complications. Tumours measuring more than 4 cm are associated with a higher risk of major complications. KEY POINTS: • Percutaneous kidney cryoablation has a low rate of complications. • Bleeding is the most frequent complication. • A tumour size superior to 4 cm is a predictive factor of major complication.

Discontinuation and non-publication of neurodegenerative disease trials: a cross-sectional analysis.

BACKGROUND AND PURPOSE: Trial discontinuation and non-publication represent major sources of research waste in clinical medicine. No previous studies have investigated non-dissemination bias in clinical trials of neurodegenerative diseases. METHODS: ClinicalTrials.gov was searched for all randomized, interventional, phase II-IV trials that were registered between 1 January 2000 and 31 December 2009 and included adults with Alzheimer's disease, motor neurone disease, multiple sclerosis or Parkinson's disease. Publications from these trials were identified by extensive online searching and contact with authors, and multiple logistic regression analysis was performed to identify characteristics associated with trial discontinuation and non-publication. RESULTS: In all, 362 eligible trials were identified, of which 12% (42/362) were discontinued. 28% (91/320) of completed trials remained unpublished after 5 years. Trial discontinuation was independently associated with number of patients (P = 0.015; more likely in trials with ≤100 patients; odds ratio 2.65, 95% confidence interval 1.21-5.78) and phase of trial (P = 0.009; more likely in phase IV than phase III trials; odds ratio 3.90, 95% confidence interval 1.41-10.83). Trial non-publication was independently associated with blinding status (P = 0.005; more likely in single-blind than double-blind trials; odds ratio 5.63, 95% confidence interval 1.70-18.71), number of centres (P = 0.010; more likely in single-centre than multi-centre trials; odds ratio 2.49, 95% confidence interval 1.25-4.99), phase of trial (P = 0.041; more likely in phase II than phase IV trials; odds ratio 2.88, 95% confidence interval 1.04-7.93) and sponsor category (P = 0.001; more likely in industry-sponsored than university-sponsored trials; odds ratio 5.05, 95% confidence interval 1.87-13.63). CONCLUSIONS: There is evidence of non-dissemination bias in randomized trials of interventions for neurodegenerative diseases. Associations with trial discontinuation and non-publication were similar to findings in other diseases. These biases may distort the therapeutic information available to inform clinical practice.

Imaging appearances at follow-up after image-guided solid-organ abdominal tumour ablation.

The role of minimally invasive, locoregional therapies in cancer is increasingly driven by the detection of small asymptomatic disease either incidentally or under surveillance for a known primary malignancy. Percutaneous image-guided ablation has become established as a parenchyma-sparing tool in the management of small volume primary and metastatic disease in the liver as well as solitary renal masses. As ablation is non-extirpative, post-ablation imaging is critical for the assessment of treatment completion, recurrence, and complications. Within established regional cancer networks, understanding of normal post-ablation imaging appearances is essential for the early identification of primary treatment failure or local recurrence, which may be amenable to repeat treatment. We provide an imaging primer of two common ablation sites - kidney and liver - focusing on normal appearances and appreciation of local disease progression.

Predictors of recurrence after radiotherapy for non-melanoma skin cancer.

Predictive factors of recurrence were examined in 448 non-melanoma skin cancers (72% basal cell carcinoma, 28% squamous cell carcinoma) treated with radiotherapy. The overall recurrence rate was 15.8% at a median follow-up of 18.4 months. In multivariate analysis, significant factors for recurrence were age (p = 0.0197), tumour size 2 cm or greater (p = 0.0095), immunosuppression (p = 0.0082), and treatment modality (p = 0.0009).

Pulmonary sequelae of severe H1N1 infection treated with high frequency oscillatory ventilation.

During the recent influenza A (H1N1) pandemic, due to severe respiratory failure many patients required treatment with alternative ventilator modalities including High Frequency Oscillatory Ventilation (HFOV). We present four such patients treated with HFOV at an academic, tertiary referral hospital in Ireland. We detail outcomes of clinical examination, pulmonary function testing, quality of life assessment and radiographic appearance on CT Thorax at follow-up at 6 months. Further clinical assessment and pulmonary function testing were performed at median 19 months (range 18-21 months) post-discharge. At initial review all patients were found to have reduced gas transfer (median predicted DLCO 74%) with preservation of lung volumes and normal spirometrical values at 6 months (median FVC 5.42L [101% predicted] and FEV14.5L [101.2% predicted] respectively), with improvements in gas transfer (median predicted DLCO 83%)at subsequent testing. Post-inflammatory changes on CT thorax at 6 months were seen in all 4 cases. To our knowledge this is the first report to document the long-term effects of severe H1N1 infection requiring high frequency oscillation on respiratory function. We conclude that the effects on respiratory function and pulmonary radiological appearance are similar to those observed following conventional treatment of Acute Respiratory Distress Syndrome [ARDS].

Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs).

These guidelines update previous guidance published in 2005. They have been revised by a group who are members of the UK and Ireland Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology, the Society for Endocrinology, the Association of Surgeons of Great Britain and Ireland (and its Surgical Specialty Associations), the British Society of Gastrointestinal and Abdominal Radiology and others. The authorship represents leaders of the various groups in the UK and Ireland Neuroendocrine Tumour Society, but a large amount of work has been carried out by other specialists, many of whom attended a guidelines conference in May 2009. We have attempted to represent this work in the acknowledgements section. Over the past few years, there have been advances in the management of neuroendocrine tumours, which have included clearer characterisation, more specific and therapeutically relevant diagnosis, and improved treatments. However, there remain few randomised trials in the field and the disease is uncommon, hence all evidence must be considered weak in comparison with other more common cancers.

A proposed new imaging pathway for patients with suspected lung cancer.

AIMS: PET-CT scans are routinely performed in patients with lung cancer after investigation by chest x-ray (CXR) and CT scan, when these have demonstrated potentially curable disease. If the majority of patients with lung cancer potentially suitable for curative treatment could be identified earlier in the diagnostic pathway on the basis of CXR findings they could be referred for PET-CT imaging without a prior CT scan. We investigated the clinical and financial implications of adopting such a strategy. MATERIALS AND METHODS: The details of 1187 patients referred with suspected lung cancer between July 2006 and August 2009 were analysed. The initial CXR and subsequent imaging of patients fit for curative treatment (Performance Status 0/1, FEV1 > 1.0) were reviewed (n = 251). The clinical and financial implications of referring patients for first line PET-CT if deemed potentially curable based on CXR findings were assessed. RESULTS: 107 of 1187 patients had potentially curable lung cancer on PS, lung function, CT and PET-CT. 96 of these 107 patients (90%) were correctly identified on CXR. 149 patients overall were diagnosed as potentially curable on CXR. Referring suitable patients for an immediate PET-CT scan resulted in a reduction in the time to complete staging investigations. CONCLUSIONS: Early PET-CT scanning for patients with suspected lung cancer, potentially suitable for curative therapy could result in more efficient staging with little additional cost.

Validation of a clinical assessment tool for spinal anaesthesia.

BACKGROUND: There is a need for a procedure-specific means of assessment of clinical performance in anaesthesia. The aim of this study was to devise a tool for assessing the performance of spinal anaesthesia, which has both content and construct validity. METHODS: The clinical assessment tool was generated using a focus group discussion of practicing anaesthetists. The tool comprised three components: a checklist of 11 pre-defined errors, two time intervals and a six-item global rating scale (GRS). Thirty-one anaesthetists at three different levels of experience underwent testing using the clinical assessment tool: novice (n=10), intermediate (n=10) and expert (n=11). RESULTS: The error checklist and GRS scores but not the time intervals were significantly different between the three groups (P<0.005). CONCLUSION: The error checklist and GRS form the basis for a procedure-specific assessment tool for spinal anaesthesia.

Early constipation predicts faster dementia onset in Parkinson's disease.

Constipation is a common but not a universal feature in early PD, suggesting that gut involvement is heterogeneous and may be part of a distinct PD subtype with prognostic implications. We analysed data from the Parkinson's Incidence Cohorts Collaboration, composed of incident community-based cohorts of PD patients assessed longitudinally over 8 years. Constipation was assessed with the MDS-UPDRS constipation item or a comparable categorical scale. Primary PD outcomes of interest were dementia, postural instability and death. PD patients were stratified according to constipation severity at diagnosis: none (n = 313, 67.3%), minor (n = 97, 20.9%) and major (n = 55, 11.8%). Clinical progression to all three outcomes was more rapid in those with more severe constipation at baseline (Kaplan-Meier survival analysis). Cox regression analysis, adjusting for relevant confounders, confirmed a significant relationship between constipation severity and progression to dementia, but not postural instability or death. Early constipation may predict an accelerated progression of neurodegenerative pathology.

A cluster of Legionnaires' disease caused by Legionella longbeachae linked to potting compost in Scotland, 2008-2009.

Three cases of Legionnaires disease caused by Legionella longbeachae Sg 1 associated with potting compost have been reported in Scotland between 2008 and 2009. The exact method of transmission is still not fully understood as Legionnaires disease is thought to be acquired by droplet inhalation. The linked cases associated with compost exposure call for an introduction of compost labelling, as is already in place in other countries where L. longbeachae outbreaks have been reported.

Progression of Neuropsychiatric Symptoms over Time in an Incident Parkinson's Disease Cohort (ICICLE-PD).

BACKGROUND: Cross-sectional studies have identified that the prevalence of neuropsychiatric symptoms (NPS) in Parkinson's disease (PD) ranges from 70-89%. However, there are few longitudinal studies determining the impact of NPS on quality of life (QoL) in PD patients and their caregivers. We seek to determine the progression of NPS in early PD. METHODS: Newly diagnosed idiopathic PD cases (n = 212) and age-matched controls (n = 99) were recruited into a longitudinal study. NPS were assessed using the Neuropsychiatric Inventory with Caregiver Distress scale (NPI-D). Further neuropsychological and clinical assessments were completed by participants, with reassessment at 18 and 36 months. Linear mixed-effects modelling determined factors associated with NPI-D and QoL over 36 months. RESULTS: Depression, anxiety, apathy and hallucinations were more frequent in PD than controls at all time points (p < 0.05). Higher motor severity at baseline was associated with worsening NPI-D scores over time (ß = 0.1, p < 0.05), but not cognition. A higher NPI total score was associated with poorer QoL at any time point (ß = 0.3, p < 0.001), but not changed in QoL scores. CONCLUSION: NPS are significantly associated with poorer QoL, even in early PD. Screening for NPS from diagnosis may allow efficient delivery of better support and treatment to patients and their families.

Feasibility of short term drainage for diagnostic thoracoscopy.

BACKGROUND AND AIM: Thoracoscopy is a diagnostic tool superior to other available techniques for the assessment of pleural effusions. There are numerous publications that describe the technique in detail but there is very little published on the optimal time of chest drain removal post procedure. Our aim was to retrospectively study all cases of diagnostic thoracoscopy and to ascertain the time of chest drain removal, length of hospital stay and associated complications. METHODS: All patients who underwent thoracoscopy during a 6-year period were identified from a computerised database. Patients who received talc for pleurodesis were excluded as they required longer drainage time. A review of the remaining patients' charts and radiology was performed to ascertain the predefined outcomes. RESULTS: 124 patients had a diagnostic thoracoscopy. The time to chest drain removal was documented as less than four hours, four to 24 hours, 24 to 48 hours and greater than 48 hours in 66 (53.2%), 29 (23.4%), 12 (9.7%) and 17 (13.7%) of patients respectively. The median length of stay for all patients was one day (interquartile range, 1-4 days). There was a statistically significant difference in overall length of hospital stay between the early (<4 hours) and late (>48 hours) chest drain removal groups, p=0.0028. The overall complication rate was 15.9%. There was no statistical difference in complication rates between the two groups. CONCLUSION: This retrospective series demonstrates that early chest drain removal post diagnostic thoracoscopy is possible and safe. This is likely to confer economic benefits.

A multicenter retrospective study investigating the role of interventional bronchoscopic techniques in the management of endobronchial lipomas.

BACKGROUND: Pulmonary lipomas are rare benign tumors that are usually found endobronchially. Undiagnosed, they can lead to the serious late sequelae associated with endobronchial obstruction. In the majority of cases, they are located in the first three subdivisions of the tracheobronchial tree, and therefore, they are amenable to endoscopic techniques for diagnostic and therapeutic purposes. OBJECTIVES: It was our aim to retrospectively study the bronchoscopic management and follow-up of a large series of endobronchial lipomas, as well as defining the demographic and endoscopic characteristics of patients. METHODS: A retrospective multicenter study was performed to identify all cases of lipomas that were treated endoscopically in 4 institutions in the period from 1981 to 2002. Demographic, radiological, endoscopic and histological data were collected. RESULTS: Thirty-eight patients were included in the study; 81.6% of cases were males and the average age was 63.5 +/- 15.2 years. The majority of the patients were symptomatic (63.2%). Lipomas were located proximally in 18 cases (47.4%) and distally in 20 subjects (52.6%). Specimens obtained by rigid bronchoscopy were diagnostic in all cases. Thirty-six out of 38 patients underwent therapeutic rigid bronchoscopy. Laser and mechanical debulking was performed in 29 cases (76.3%), cryotherapy and mechanical debulking in 7 subjects (18.4%), and mechanical debulking alone in 2 cases (5.3%). No cases of recurrence occurred during the follow-up period. CONCLUSIONS: This study demonstrates that endoscopic techniques are effective for the diagnosis and treatment of endobronchial lipomas when there is no evidence of severe distal bronchiectasis. This should be the treatment of choice after a full clinicoradiological evaluation.

[A rare cause of stridor in a 59 year old woman in intensive care]. / Stridor d'étiologie rare en post-réanimation chez une patiente de 59 ans.

INTRODUCTION: Stridor in the post extubation period occurs frequently and is most commonly caused by laryngeal oedema. During this period, the trachea can also be obstructed by pseudomembranes. CASE REPORT: We report the case of a 59 year old woman who required re-intubation, 15 days after extubation because of the acute onset of severe respiratory distress secondary to pseudomembranes in her trachea. CONCLUSION: It is essential that physicians who care for patients during the post extubation period are aware of this severe and life threatening cause of stridor. Definitive treatment with the rigid bronchoscope allows for rapid recanalisation of the airway.

Treating recurrent cases of squamous cell carcinoma with radiotherapy.

Patients with chronic lymphocytic leukemia (CLL) are at a significantly increased risk of developing cutaneous squamous cell carcinoma (SCC), in part because of their impaired immunosurveillance. Here, we report the cases of 4 patients with CLL who had locally aggressive cutaneous scc managed with radiotherapy for local recurrence following surgical excision. All tumours were located in the head-and-neck region. All patients initially achieved complete regression of disease; however, 2 had local recurrence a mean of 8 months after treatment completion. One patient died from progressive SCC. Our findings agree with the high rates reported in literature of multiple tumours, local recurrence, metastases, and mortality from scc in patients with cll. Radiotherapy plays an important role in patient management, and it is the recommended treatment modality when complete surgical excision of disease would result in anatomic and functional defects. Radiotherapy is often used in the case of local recurrence after one or more attempts at surgical excision. Dose escalation through intensity-modulated radiotherapy, hyperfractionation, or novel treatment techniques such as high-intensity focused ultrasound may be explored to improve local control of scc lesions. To optimize patient outcomes, cutaneous SCC arising in patients with a history of cll should be managed and followed in a multidisciplinary clinic, with regular skin surveillance and prompt treatment.