Proglucagon-derived peptides do not significantly affect acute exocrine pancreas in rat

Reports have suggested a link between treatment with glucagon-like peptide 1 (GLP-1) analogs and an increased risk of pancreatitis. Oxyntomodulin, a dual agonist of both GLP-1 and glucagon receptors, is currently being investigated as a potential antiobesity therapy, but little is known about its pancreatic safety. The aim of the study was to investigate the acute effect of oxyntomodulin and other proglucagon-derived peptides on the rat exocrine pancreas.Glucagon-like peptide 1, oxyntomodulin, glucagon, and exendin-4 were infused into anesthetized rats to measure plasma amylase concentration changes. In addition, the effect of each peptide on both amylase release and proliferation in rat pancreatic acinar (AR42J) and primary isolated ductal cells was determined.Plasma amylase did not increase postpeptide infusion, compared with vehicle and cholecystokinin; however, oxyntomodulin inhibited plasma amylase when coadministered with cholecystokinin. None of the peptides caused a significant increase in proliferation rate or amylase secretion from acinar and ductal cells.The investigated peptides do not have an acute effect on the exocrine pancreas with regard to proliferation and plasma amylase, when administered individually. Oxyntomodulin seems to be a potent inhibitor of amylase release, potentially making it a safer antiobesity agent regarding pancreatitis, compared with GLP-1 agonists

Evaluation of nationwide referral pathways, investigation and treatment of suspected cauda equina syndrome in the United Kingdom.

Purpose: Cauda equina syndrome (CES) is a spinal emergency with clinical symptoms and signs that have low diagnostic accuracy. National guidelines in the United Kingdom (UK) state that all patients should undergo an MRI prior to referral to specialist spinal units and surgery should be performed at the earliest opportunity. We aimed to evaluate the current practice of investigating and treating suspected CES in the UK. Materials and Methods: A retrospective, multicentre observational study of the investigation and management of patients with suspected CES was conducted across the UK, including all patients referred to a spinal unit over 6 months between 1st October 2016 and 31st March 2017. Results: A total of 28 UK spinal units submitted data on 4441 referrals. Over half of referrals were made without any previous imaging (n = 2572, 57.9%). Of all referrals, 695 underwent surgical decompression (15.6%). The majority of referrals were made out-of-hours (n = 2229/3517, 63.4%). Patient location and pre-referral imaging were not associated with time intervals from symptom onset or presentation to decompression. Patients investigated outside of the spinal unit experienced longer time intervals from referral to undergoing the MRI scan. Conclusions: This is the largest known study of the investigation and management of suspected CES. We found that the majority of referrals were made without adequate investigations. Most patients were referred out-of-hours and many were transferred for an MRI without subsequently requiring surgery. Adherence to guidelines would reduce the number of referrals to spinal services by 72% and reduce the number of patient transfers by 79%

Molecular study of the perforin gene in familial hematological malignancies

Perforin gene (PRF1) mutations have been identified in some patients diagnosed with the familial form of hemophagocytic lymphohistiocytosis (HLH) and in patients with lymphoma. The aim of the present study was to determine whether patients with a familial aggregation of hematological malignancies harbor germline perforin gene mutations. For this purpose, 81 unrelated families from Tunisia and France with aggregated hematological malignancies were investigated. The variants detected in the PRF1 coding region amounted to 3.7% (3/81). Two of the three variants identified were previously described: the p.Ala91Val pathogenic mutation and the p.Asn252Ser polymorphism. A new p.Ala 211Val missense substitution was identified in two related Tunisian patients. In order to assess the pathogenicity of this new variation, bioinformatic tools were used to predict its effects on the perforin protein structure and at the mRNA level. The segregation of the mutant allele was studied in the family of interest and a control population was screened. The fact that this variant was not found to occur in 200 control chromosomes suggests that it may be pathogenic. However, overexpression of mutated PRF1 in rat basophilic leukemia cells did not affect the lytic function of perforin differently from the wild type protein

CovidNeuroOnc: A UK multicenter, prospective cohort study of the impact of the COVID-19 pandemic on the neuro-oncology service

BackgroundThe COVID-19 pandemic has profoundly affected cancer services. Our objective was to determine the effect of the COVID-19 pandemic on decision making and the resulting outcomes for patients with newly diagnosed or recurrent intracranial tumors.MethodsWe performed a multicenter prospective study of all adult patients discussed in weekly neuro-oncology and skull base multidisciplinary team meetings who had a newly diagnosed or recurrent intracranial (excluding pituitary) tumor between 01 April and 31 May 2020. All patients had at least 30-day follow-up data. Descriptive statistical reporting was used.ResultsThere were 1357 referrals for newly diagnosed or recurrent intracranial tumors across 15 neuro-oncology centers. Of centers with all intracranial tumors, a change in initial management was reported in 8.6% of cases (n = 104/1210). Decisions to change the management plan reduced over time from a peak of 19% referrals at the start of the study to 0% by the end of the study period. Changes in management were reported in 16% (n = 75/466) of cases previously recommended for surgery and 28% of cases previously recommended for chemotherapy (n = 20/72). The reported SARS-CoV-2 infection rate was similar in surgical and non-surgical patients (2.6% vs. 2.4%, P > .9).ConclusionsDisruption to neuro-oncology services in the UK caused by the COVID-19 pandemic was most marked in the first month, affecting all diagnoses. Patients considered for chemotherapy were most affected. In those recommended surgical treatment this was successfully completed. Longer-term outcome data will evaluate oncological treatments received by these patients and overall survival

CSF Rhinorrhea After Endonasal Intervention to the Skull Base (CRANIAL) — Part 2:Impact of COVID-19

Background During the pandemic, there has been a concern about the increased risk of perioperative mortality for patients with COVID-19, and the transmission risk to healthcare workers, particularly during endonasal neurosurgical operations. The Pituitary Society produced recommendations to guide management during this era. We sought to assess contemporary neurosurgical practice and the impact of COVID-19. Methods A multicentre, prospective, observational cohort study was conducted at twelve tertiary neurosurgical units (UK and Ireland). Data were collected from March 23rd-July 31st, 2020 inclusive. Data points collected were patient demographics, pre-operative COVID-19 testing, intra-operative operative modifications, and 30-day COVID infection rates. Results 124 patients were included. 116 patients (n=116/124, 94%) underwent COVID-19 testing pre-operatively (TSA: 97/105, 92%; EEA: 19/19, 100%). One patient (n=1/115, 1%) tested positively for COVID-19 pre-operatively, requiring a delay of operation until the infection was confirmed as resolved. Asides from transient diabetes insipidus; no other complications were reported for this case. All theatre staff wore at least level 2 PPE. Adaptations to surgical techniques included minimising drilling, draping modifications, and using nasal iodine wash. At 30 days postoperatively, there was no evidence of COVID infection (symptoms or on formal testing) in our cohort, and no mortality. Conclusions Preoperative screening protocols and operative modifications have facilitated endonasal neurosurgery during the COVID-19 pandemic, with Pituitary Society guidelines followed for the majority of these operations. There was no evidence of COVID infection in our cohort, and no mortality, supporting the use of risk mitigation strategies to continue endonasal neurosurgery in subsequent pandemic waves

CSF Rhinorrhoea After Endonasal Intervention to the Skull Base (CRANIAL) - Part 1: Multicenter Pilot Study

Background: CRANIAL (CSF Rhinorrhoea After Endonasal Intervention to the Skull Base) is a prospective, multicentre observational study seeking to determine: (1) the scope of skull base repair methods used; and (2) corresponding rates of postoperative CSF rhinorrhoea in endonasal transsphenoidal (TSA) expanded endonasal approaches (EEA) for skull base tumours. We sought to pilot the project - assessing the feasibility and acceptability by gathering preliminary data. / Methods: A prospective, observational cohort pilot study was carried out at twelve tertiary UK neurosurgical units. Feedback regarding project positives and challenges were qualitatively analysed. / Results: 187 cases were included, 159 TSA (85%) and 28 EEA (15%). The most common pathologies included: pituitary adenomas (n=141/187), craniopharyngiomas (n=13/187) and skull-base meningiomas (n=4/187). The most common skull base repair techniques used were tissue glues (n=132/187, most commonly Tisseel®), grafts (n=94/187, most commonly fat autograft or Spongostan™) and vascularised flaps (n=51/187, most commonly nasoseptal). These repairs were most frequently supported by nasal packs (n=125/187) and lumbar drains (n=22/187). Biochemically-confirmed CSF rhinorrhoea occurred in 6/159 (3.8%) TSA and 2/28 (7.1%) EEA. Four TSA (3%) and two EEA (7%) cases required operative management for CSF rhinorrhoea (CSF diversion or direct repair). Qualitative feedback was largely positive (themes included: user-friendly and efficient data collection, strong support from senior team members) demonstrating acceptability. / Conclusions: Our pilot experience highlights the acceptability and feasibility of CRANIAL. There is a precedent for multicentre dissemination of this project, in order to establish a benchmark of contemporary skull base neurosurgery practice, particularly with respect to EEA cases

CSF Rhinorrhoea After Endonasal Intervention to the Skull Base (CRANIAL) - Part 1:Multicenter Pilot Study

Background CRANIAL (CSF Rhinorrhoea After Endonasal Intervention to the Skull Base) is a prospective, multicentre observational study seeking to determine: (1) the scope of skull base repair methods used; and (2) corresponding rates of postoperative CSF rhinorrhoea in endonasal transsphenoidal (TSA) expanded endonasal approaches (EEA) for skull base tumours. We sought to pilot the project - assessing the feasibility and acceptability by gathering preliminary data. Methods A prospective, observational cohort pilot study was carried out at twelve tertiary UK neurosurgical units. Feedback regarding project positives and challenges were qualitatively analysed. Results 187 cases were included, 159 TSA (85%) and 28 EEA (15%). The most common pathologies included: pituitary adenomas (n=141/187), craniopharyngiomas (n=13/187) and skull-base meningiomas (n=4/187). The most common skull base repair techniques used were tissue glues (n=132/187, most commonly Tisseel®), grafts (n=94/187, most commonly fat autograft or Spongostan™) and vascularised flaps (n=51/187, most commonly nasoseptal). These repairs were most frequently supported by nasal packs (n=125/187) and lumbar drains (n=22/187). Biochemically-confirmed CSF rhinorrhoea occurred in 6/159 (3.8%) TSA and 2/28 (7.1%) EEA. Four TSA (3%) and two EEA (7%) cases required operative management for CSF rhinorrhoea (CSF diversion or direct repair). Qualitative feedback was largely positive (themes included: user-friendly and efficient data collection, strong support from senior team members) demonstrating acceptability. Conclusions Our pilot experience highlights the acceptability and feasibility of CRANIAL. There is a precedent for multicentre dissemination of this project, in order to establish a benchmark of contemporary skull base neurosurgery practice, particularly with respect to EEA cases. Keywords Cerebrospinal fluid rhinorrhoeaCSFCerebrospinal fluid leakskull base surgeryendoscopic endonasalEE

Variation in postoperative outcomes of patients with intracranial tumors: insights from a prospective international cohort study during the COVID-19 pandemic

Background: This study assessed the international variation in surgical neuro-oncology practice and 30-day outcomes of patients who had surgery for an intracranial tumor during the COVID-19 pandemic. Methods: We prospectively included adults aged ≥18 years who underwent surgery for a malignant or benign intracranial tumor across 55 international hospitals from 26 countries. Each participating hospital recorded cases for 3 consecutive months from the start of the pandemic. We categorized patients’ location by World Bank income groups (high [HIC], upper-middle [UMIC], and low- and lower-middle [LLMIC]). Main outcomes were a change from routine management, SARS-CoV-2 infection, and 30-day mortality. We used a Bayesian multilevel logistic regression stratified by hospitals and adjusted for key confounders to estimate the association between income groups and mortality. Results: Among 1016 patients, the number of patients in each income group was 765 (75.3%) in HIC, 142 (14.0%) in UMIC, and 109 (10.7%) in LLMIC. The management of 200 (19.8%) patients changed from usual care, most commonly delayed surgery. Within 30 days after surgery, 14 (1.4%) patients had a COVID-19 diagnosis and 39 (3.8%) patients died. In the multivariable model, LLMIC was associated with increased mortality (odds ratio 2.83, 95% credible interval 1.37–5.74) compared to HIC. Conclusions: The first wave of the pandemic had a significant impact on surgical decision-making. While the incidence of SARS-CoV-2 infection within 30 days after surgery was low, there was a disparity in mortality between countries and this warrants further examination to identify any modifiable factors