CXCL9 inhibition does not ameliorate disease in murine models of both primary and secondary hemophagocytic lymphohistiocytosis.

Hemophagocytic Lymphohistiocytosis (HLH) is a group of disorders culminating in systemic inflammation and multi-organ failure with high incidence of hepatic dysfunction. Overproduction of IFN-γ is the main immunopathological driver in this disorder. Monokine induced by IFN-γ (CXCL9) serves as a biomarker for disease activity and response to treatment in this disorder. However, very little is understood about the actual functional role of CXCL9 in pathogenesis in HLH. In the current study, we sought to determine the role of CXCL9 in pathogenesis in murine models of both Familial HLH (prf1-/-) and Toll Like Receptor (TLR) 9 repeated stimulation induced Macrophage Activation Syndrome (MAS), a form of secondary HLH. FHL and MAS were induced in both CXCL9 genetically deficient mice (cxcl9-/-) and controls as well as using AMG487, a pharmacological antagonist of the CXCL9 receptor, CXCR3. Results showed that CXCL9 genetic deficiency did not improve disease parameters or hepatitis in both models. Consistent with genetic ablation of CXCL9, inhibition of its receptor, CXCR3, by AMG487 did not show any significant effects in the FHL model. Taken together, inhibition of CXCL9-CXCR3 interaction does not ameliorate HLH physiology in general, or hepatitis as a classical target organ of disease.

Canadian public perceptions and experiences with information during the COVID-19 pandemic: strategies to optimize future risk communications.

BACKGROUND: The COVID-19 pandemic accelerated the spread of misinformation worldwide. The purpose of this study was to explore perceptions of misinformation and preferred sources of obtaining COVID-19 information from those living in Canada. In particular, we sought to explore the perceptions of East Asian individuals in Canada, who experienced stigma related to COVID-19 messaging. METHODS: We conducted a qualitative thematic analysis study. Interviews were offered in English, Mandarin and Cantonese. Interviewers probed for domains related to knowledge about COVID-19, preferred sources of information, perceived barriers and facilitators of misinformation, and preferences for communication during a health emergency. Interviews were recorded, translated, transcribed verbatim and analyzed using a framework approach. Transcripts were independently double-coded until > 60% agreement was reached. This study received research ethics approval. RESULTS: Fifty-five interviews were conducted. The majority of participants were women (67%); median age was 52 years. 55% of participants were of East-Asian descent. Participants obtained information about COVID-19 from diverse English and non-English sources including news media, government agencies or representatives, social media, and personal networks. Challenges to seeking and understanding information included: encountering misinformation, making sense of evolving or conflicting public health guidance, and limited information on topics of interest. 65% of participants reported encountering COVID-19  misinformation. East Asian participants called on government officials to champion messaging to reduce stigmatizing and racist rhetoric and highlighted the importance of having accessible, non-English language information sources. Participants provided recommendations for future public health communications guidance during health emergencies, including preferences for message content, information messengers, dissemination platforms and format of messages. Almost all participants preferred receiving information from the Canadian government and found it helpful to utilize various mediums and platforms such as social media and news media for future risk communication, urging for consistency across all platforms. CONCLUSIONS: We provide insights on Canadian experiences navigating COVID-19 information, where more than half perceived encountering misinformation on platforms when seeking COVID-19 information . We provide recommendations to inform public health communications during future health emergencies.

Difficulty in Diagnosing Rare Cardiac Tumors: A Case Series.

Primary cardiac tumors are rare because metastatic lesions from distant sites account for most masses. We are reporting two cases of malignant intracardiac masses with their diagnostic dilemma. Our first patient is a 72-year-old male with a pertinent history of desmoplastic and spindle cell melanoma who presented after his surveillance positron emission tomography (PET) scan showed a hypermetabolic lesion in the inferior pericardium. The initial impression for this mass is recurrent malignant melanoma. After an initial negative endometrial biopsy, the patient underwent debulking surgery, and pathology revealed high-grade spindle cell sarcoma. The patient underwent chemotherapy but had a disease progression and ultimately elected hospice care. Our second patient is a 75-year-old male with a history of stage IB adenocarcinoma of the lung who presented with progressive dyspnea. An echocardiogram revealed a moderate-sized left ventricular mass. Initial assessment based on tumor morphology and location suggested possible cardiac sarcoma. However, the patient's subsequent cardiac biopsy revealed small cell carcinoma, likely of primary cardiac origin, as no other primary nidus of the tumor was seen. Based on this result, the patient has been started on carboplatin, etoposide, and atezolizumab and responded well as of the writing of this manuscript. Given the rarity of malignant primary cardiac tumors and their variable clinical presentation, intracardiac masses are often diagnosed incidentally. In addition, given the high risk of biopsy for intracardiac masses, a presumptive diagnosis is rendered via imaging techniques. However, most of these tumors have no pathognomonic imaging findings, and their diagnosis relies heavily on physician interpretation and experience. Our case series illustrated the unpredictable nature of noninvasive methods and that even endometrial biopsy can return a false negative. Therefore, it is essential to be persistent in obtaining a pathological diagnosis, especially if the clinical picture is unclear. While these more invasive methods present the challenge of identifying whether the procedure is truly needed and locating a skilled operator, it could change the diagnosis entirely and open the patient up to new therapies.

Exploring perceptions and experiences of stigma in Canada during the COVID-19 pandemic: a qualitative study.

Background: The COVID-19 pandemic fueled stigmatization and discrimination, particularly towards individuals of Chinese or East Asian ethnicity. We conducted interviews with members of the public in Canada in order to describe and understand stigma perceptions and experiences during the COVID-19 pandemic. Methods: We used a phenomenological approach to describe stigma experiences of Canadian residents during the COVID-19 pandemic and compared the stigma perceptions and experiences of East Asian and non-East Asian individuals. Participants were invited to take part in a single, semi-structured interview. The interview guide was rooted in the Health Stigma and Discrimination Framework (HSDF). Interviews were conducted in English, Mandarin, and Cantonese. Following participant consent, interviews were audio recorded and transcribed verbatim. Data were double coded and analyzed using qualitative content analysis guided by a framework approach. Results: A total of 55 interviews were conducted between May and December 2020. Fifty-five percent of the sample identified as East Asian, 67.3% identified as women, and mean age was 52 years (range 20-76). Fear of infection, fear of social and economic ramifications, and blame for COVID-19 were reported drivers of stigma. Participants described preexisting perceptions on cultural norms and media influence as facilitators of stigma that propagated harmful stereotypes, particularly against Chinese and East Asian individuals. Participants observed or experienced stigmatization towards place of residence, race/ethnicity, culture, language, occupation, and age. Stigma manifestations present in the public and media had direct negative impacts on East Asian, particularly Chinese, participants, regardless of whether or not they personally experienced discrimination. Conclusions: We used the HSDF as a rooting framework to describe perceptions and impact of stigma, particularly as they related to race/ethnicity-based stigmatization in Canada. Participants reported a number of drivers and facilitators of stigma that impacted perceptions and experiences. These findings should be used to develop sustained strategies to mitigate stigma during public health emergencies or other major crises. Supplementary Information: The online version contains supplementary material available at 10.1186/s44263-023-00020-7.

Does reverse mentoring work in the NHS: a feasibility study of clinicians in practice.

OBJECTIVE: To assess the risks and benefits of reverse mentoring of consultants by junior doctors. DESIGN: A feasibility study divided into two phases: first a semistructured interview where performance of participating consultants was assessed by junior doctors and then a second phase allowing for feedback to be given on a one-to-one basis. Data collected through questionnaires with free text questions and Likert scores. SETTING: Tertiary teaching hospital in the UK. PARTICIPANTS: Six junior doctors (66.6% male, age range 31-40 years) and five consultants (80% male, age range 35-65 years and consultants for 5-20 years). INTERVENTION: Reverse mentoring session. MAIN OUTCOME MEASURE: The concerns and/or benefits of the process of reverse mentoring. Confidence was assessed in 7 domains: clinical practice, approach to juniors, approachability, use of technology, time management, strengths and areas for improvement using Likert scales giving a total out of 35. RESULTS: The most common concerns cited were overcoming the hierarchical difference and a selection bias in both mentors and mentees. However, no participant experienced this hierarchical difference through the reverse mentoring process and no relationships were negatively affected. Mentors became more confident in feeding back to seniors (23 vs 29 out of 35, p=0.04) most evident in clinical practice and areas to improve (3 vs 4 out of 5, p=0.041 and 3 vs 5 out of 5, p=0.041, respectively). CONCLUSION: We present the first study of reverse mentoring in an NHS clinical setting. Initial concerns with regard to damaged relationships and hierarchical gradients were not experienced and all participants perceived that they benefited from the process. Reverse mentoring can play a role in engaging and training future leaders at junior stages and provide a means for consultants to receive valuable feedback from junior colleagues.

Haber-independent, asymmetric synthesis of the marine alkaloid epi-leptosphaerin from a chitin-derived chiral pool synthon.

Chitin-derived platforms are emerging as valuable chemical entities for the construction of nitrogenous fine chemicals in processes independent of Haber ammonia. However, much of the work in this area has focused on achiral platforms that limit routine entry into enantiopure, bio-based N-chemical space. Herein, dihydroxyethyl acetamidofuran (Di-HAF), a chiral synthon readily available from chitin, has been transformed into the marine alkaloid epi-leptosphaerin. This work extends the fledgling Haber-independent synthesis concept to enantiopure chemical space not routinely accessible from existing achiral platforms.

Performance measures for the SACRED team-centered approach to advanced gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative.

The European Society of Gastrointestinal Endoscopy and United European Gastroenterology have defined performance measures for upper and lower gastrointestinal, pancreaticobiliary, and small-bowel endoscopy. Quality indicators to guide endoscopists in the growing field of advanced endoscopy are also underway. We propose that equal attention is given to developing the entire advanced endoscopy team and not the individual endoscopist alone.We suggest that the practice of teams intending to deliver high quality advanced endoscopy is underpinned by six crucial principles concerning: selection, acceptance, complications, reconnaissance, envelopment, and documentation (SACRED).

Mathematical Models for the Skin to Lumbosacral Epidural Distance in Dogs: A Cadaveric Computed-Tomography Study.

This study aimed to validate previously published computed tomography (CT) derived mathematical equations with the true skin to lumbosacral epidural distance (SLED) in dog cadavers. Phase 1: The lumbar region of 11 dog cadavers were scanned in sternal recumbency to determine the effect of cranial, neutral, and caudal pelvic limb positioning on the CT derived lumbosacral epidural distance (CLED). Phase 2: The epidural space was determined using contrast epidurography, and the SLED was analysed against the mathematical equations using a body condition score (BCS) and either the cadaveric occipital-coccygeal length (OCL) (Equation (1): = 7.3 + 0.05*OCL + 16.45*BCS) or the ilium wing distance (IWD) (Equation (2): = 3.5 + 0.56*IWD + 16.6*BCS). There were no differences detected between the pelvic limb positions and the CLED. Both equations demonstrated strong correlations (Equation (1): r = 0.7196; Equation (2): r = 0.7590) with the SLED. The level of agreement was greater for Equation (1) than with Equation (2) (concordance coefficient 0.6061 and 0.3752, respectively). Equation (1) also demonstrated a closer fit to the concordance line compared with Equation (2) (bias correction factor 0.8422 and 0.4960, respectively). Further studies in live anaesthetised dogs will help to determine the usefulness of the pre-procedural knowledge when performing lumbosacral epidurals.

Gynaecomastia in a male neutered cat with an adrenal tumour and associated hyperprogesteronism, hypercortisolism and hyperaldosteronism.

CASE SUMMARY: A 7-year-old male neutered domestic longhair cat was presented with chronic progressive gynaecomastia, polydipsia, polyphagia, weight loss and poor fur regrowth. Sexualised behavioural changes were not reported and virilisation was not present on physical examination. Pertinent haematology, biochemistry and urinalysis findings at the time of referral included mild hypokalaemia. Left adrenomegaly and mild prostatomegaly were identified on a CT scan. Evaluation of adrenal hormones with a low-dose dexamethasone suppression test, serum progesterone, testosterone, oestradiol, plasma aldosterone, renin, plasma metanephrine and normetanephrine measurement supported a diagnosis of hyperprogesteronism, hyperaldosteronism and hypercortisolism. Adrenalectomy was performed and histopathology was consistent with an adrenocortical tumour. Clinical signs and hormone elevations resolved postoperatively. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the second report of gynaecomastia secondary to an adrenal tumour in a male neutered cat and the first associated with hyperprogesteronism.

What is the Optimal Method Assessing for Persistent Villous Atrophy in Adult Coeliac Disease?

BACKGROUND AND AIMS: Methods of assessing gluten-free diet (GFD) adherence in adults with coeliac disease (CD) include serological testing, dietitian evaluation, questionnaires and repeat duodenal biopsies. Persisting villous atrophy (VA) is associated with CD complications, however gastroscopy with biopsies is expensive and invasive. This study aimed to assess the abilities of a duodenal bulb (D1) biopsy and the Celiac Dietary Adherence Test (CDAT) to detect persisting VA in adults with CD. METHODS: A prospective observational study of adult CD patients referred for follow-up duodenal biopsies was performed. Quadrantic biopsies were taken from the second part of the duodenum (D2), in addition to a D1 biopsy. Patients underwent follow-up serological testing, and completed the CDAT and Biagi Score. These non-invasive adherence markers were compared against duodenal histology. RESULTS: 368 patients (mean age 51.0 years, 70.1% female) had D1 and D2 biopsies taken at follow-up gastroscopy. Compared to D2 biopsies alone, additional D1 biopsies increased detection of VA by 10.4% (p<0.0001). 201 patients (mean age 50.3 years, 67.7% female) completed adherence questionnaires and serology. When detecting VA, sensitivities and specificities of these markers were 39.7% and 94.2% for IgA- tTG, 38.1% and 96.4% for IgA-EMA, 55.6% and 52.2% for CDAT and 20.6% and 96.4% for the Biagi score. CONCLUSIONS: Bulbar biopsies increase detection of persisting VA by 10.4%. Serology, CDAT and Biagi performed poorly when predicting VA. The gold standard for predicting persisting VA remains repeat biopsy.

Lithium-Sulfur Battery Cathode Design: Tailoring Metal-Based Nanostructures for Robust Polysulfide Adsorption and Catalytic Conversion.

Lithium-sulfur (Li-S) batteries have a high specific energy capacity and density of 1675 mAh g-1 and 2670 Wh kg-1 , respectively, rendering them among the most promising successors for lithium-ion batteries. However, there are myriads of obstacles in the practical application and commercialization of Li-S batteries, including the low conductivity of sulfur and its discharge products (Li2 S/Li2 S2 ), volume expansion of sulfur electrode, and the polysulfide shuttle effect. Hence, immense attention has been devoted to rectifying these issues, of which the application of metal-based compounds (i.e., transition metal, metal phosphides, sulfides, oxides, carbides, nitrides, phosphosulfides, MXenes, hydroxides, and metal-organic frameworks) as sulfur hosts is profiled as a fascinating strategy to hinder the polysulfide shuttle effect stemming from the polar-polar interactions between the metal compounds and polysulfides. This review encompasses the fundamental electrochemical principles of Li-S batteries and insights into the interactions between the metal-based compounds and the polysulfides, with emphasis on the intimate structure-activity relationship corroborated with theoretical calculations. Additionally, the integration of conductive carbon-based materials to ameliorate the existing adsorptive abilities of the metal-based compound is systematically discussed. Lastly, the challenges and prospects toward the smart design of catalysts for the future development of practical Li-S batteries are presented.

Magnetic resonance imaging in dogs with neuroangiostrongyliasis (rat lungworm disease).

The magnetic resonance imaging (MRI) appearance of the brain and spinal cord in humans with neuroangiostrongyliasis (NA) due to Angiostrongylus cantonensis infection has been well reported. Equivalent studies in animals are lacking. This case series describes clinical and MRI findings in 11 dogs with presumptively or definitively diagnosed NA. MRI of the brain and/or spinal cord was performed using high-field (1.5 T) or low-field (0.25 T) scanners using various combinations of transverse, sagittal, dorsal and three-dimensional (3D) T1-weighted (T1W), transverse, sagittal and dorsal T2-weighted (T2W), T2W fluid-attenuated inversion recovery (FLAIR) and T2*-weighted (T2*W) gradient echo (GRE), dorsal T2W short tau inversion recovery (STIR) and post-gadolinium transverse, sagittal, dorsal and 3D T1W and transverse T2W FLAIR sequences. In 4/6 cases where the brain was imaged, changes consistent with diffuse meningoencephalitis were observed. Evidence of meningeal involvement was evident even when not clinically apparent. The spinal cord was imaged in 9 dogs, with evidence of meningitis and myelitis detected in regions consistent with the observed neuroanatomical localization. Pathognomonic changes of neural larva migrans, as described in some human patients with NA, were not detected. NA should be considered in the differential diagnosis of dogs with MRI evidence of focal or diffuse meningitis, myelitis and/or encephalitis, especially in areas where A. cantonensis is endemic. If not precluded by imaging findings suggestive of brain herniation, cerebrospinal fluid (CSF) collection for cytology, fluid analysis, real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) testing should be considered mandatory in such cases after the MRI studies.

Changes in the upper airway, hyoid bone and craniofacial morphology between patients treated with headgear activator and Herbst appliance: A retrospective study on lateral cephalometry.

BACKGROUND: The present study compared the treatment changes in the upper airway, hyoid bone position and craniofacial morphology between two groups of children with skeletal class II malocclusion treated with the headgear activator (HGA) and Herbst appliance (Herbst). SETTING AND SAMPLE POPULATION: Orthodontic population from the Faculty of Dentistry of the University of Hong Kong. METHODS: Thirty-four skeletal class II patients treated with the HGA (17 patients, mean age 10.6 ± 1.5 years) and the Herbst (17 patients, mean age 11.0 ± 1.4 years) were matched for sex, age, overjet, skeletal class and mandibular divergence. The patients received lateral cephalometric radiographs (LCRs) at the beginning of treatment (T1 ), after treatment (T2 ) and at follow-up (T3 ). In the HGA group, patients underwent LCRs 7 months before the beginning of treatment (T0 ), which were used as growth reference for intra-group comparison. Paired Student's t tests were used for intra- and inter-group comparisons (α = .05). RESULTS: Treatment changes (T2 -T1 ) did not differ significantly between the groups. However, at follow-up (T3 -T1 ) the Herbst group showed a smaller increase than the HGA group in the vertical position of the hyoid bone relative to the Frankfort plane (P = .013) and mandibular plane (P = .013). CONCLUSIONS: There were no significant differences in the upper airway, hyoid bone position and craniofacial morphology between the groups at the end of treatment. However, the Herbst may provide better long-term control of the vertical position of the hyoid bone than the HGA in children with skeletal class II malocclusion.

Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts.

OBJECTIVE: We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients. DESIGN: The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD. RESULTS: Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively. CONCLUSION: Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD.

Ventilated postmortem computed tomography to evaluate the lungs of dogs with and without focal lung lesions.

OBJECTIVE: To identify the optimal ventilation pressure for ventilated postmortem CT assessment of the lungs in cadaveric dogs and compare the optimal ventilation pressures between dogs with and without focal lung lesions. SAMPLE: 12 cadaveric dogs. PROCEDURES: CT was performed with dogs positioned in sternal recumbency within 30 to 180 minutes after death. After orotracheal intubation, lungs were aerated to ventilation pressures of 0, 10, 15, 20, 25, 30, and 35 cm H2O. Lung attenuation measurements were made at 5 predetermined anatomical locations with use of a multi-image analysis graphic user interface tool. Lungs were considered hyperaerated (-1000 to -901 HU), normo-aerated (-900 to -501 HU), poorly aerated (-500 to -101 HU), and nonaerated (-100 to 100 HU) on the basis of lung attenuation values. Optimal ventilation pressure was defined as the pressure at which the percentage of normo-aerated lung was greatest. For analysis, dogs were assigned to one group when focal lung lesions were evident and to another group when lesions were not evident. RESULTS: Median optimal ventilation pressure was significantly higher for those dogs with lung lesions (35 cm H2O), compared with those without (25 cm H2O). CONCLUSIONS AND CLINICAL RELEVANCE: A ventilation pressure of 35 cm H2O may be considered for ventilated postmortem CT to determine the presence of focal lung lesions; however, further investigation is required.

Metastatic Pancreatic Cancer: ASCO Guideline Update.

PURPOSE: The aim of this work was to provide an update to the ASCO guideline on metastatic pancreatic cancer pertaining to recommendations for therapy options after first-line treatment. METHODS: ASCO convened an Expert Panel and conducted a systematic review to update guideline recommendations for second-line therapy for metastatic pancreatic cancer. RESULTS: One randomized controlled trial of olaparib versus placebo, one report on phase I and II studies of larotrectinib, and one report on phase I and II studies of entrectinib met the inclusion criteria and inform the guideline update. RECOMMENDATIONS: New or updated recommendations for germline and somatic testing for microsatellite instability high/mismatch repair deficiency, BRCA mutations, and TRK alterations are provided for all treatment-eligible patients to select patients for recommended therapies, including pembrolizumab, olaparib, larotrectinib, or entrectinib, or potential clinical trials. The Expert Panel continues to endorse the remaining recommendations for second-line chemotherapy, as well as other recommendations related to treatment, follow-up, and palliative care from the 2018 version of this guideline. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Coeliac disease detection with an IgA/IgG-deamidated gliadin peptide based point of care test in community pharmacies.

Background Coeliac disease affects 1% of the population, but 75% remain undiagnosed. Objective To conduct a case finding feasibility and efficacy study for the detection of coeliac disease in community pharmacies. Setting Six community pharmacies across Sheffield, UK. Method A prospective study was performed using a point of care test, Simtomax® (IgA/IgG-deamidated gliadin peptide) (C-test) in pharmacies. Pharmacy customers with symptoms suggestive of or risk factors for coeliac disease were tested with the C-test. Positive individuals were referred for a gastroscopy with duodenal biopsies alongside conventional serology. People with known coeliac disease, those on a gluten free diet or those who were investigated for coeliac disease were excluded. Main outcome measure The case detection rate and the uptake rate of the C-test and gastroscopies. Results Five-hundred participants fulfilled the inclusion criteria and were tested with the C-test (369 females, 73.8%; age range 18-87, median 49). The C-test uptake rate was 63%, and the positive rate was 7.2% (36/500). Twenty-seven positive participants (75%) underwent further investigations, confirming three new cases of coeliac disease (0.6%). Conclusion It was feasible to use the C-test as a case finding tool in pharmacies. There was good uptake for the C-test, although the case detection rate and the test specificity were low. Based on this, the C-test has a limited role in case finding in a community pharmacy setting.

Office-Based Point of Care Testing (IgA/IgG-Deamidated Gliadin Peptide) for Celiac Disease.

OBJECTIVES: Celiac disease (CD) is common yet under-detected. A point of care test (POCT) may improve CD detection. We aimed to assess the diagnostic performance of an IgA/IgG-deamidated gliadin peptide (DGP)-based POCT for CD detection, patient acceptability, and inter-observer variability of the POCT results. METHODS: From 2013-2017, we prospectively recruited patients referred to secondary care with gastrointestinal symptoms, anemia and/or weight loss (group 1); and patients with self-reported gluten sensitivity with unknown CD status (group 2). All patients had concurrent POCT, IgA-tissue transglutaminase (IgA-TTG), IgA-endomysial antibodies (IgA-EMA), total IgA levels, and duodenal biopsies. Five hundred patients completed acceptability questionnaires, and inter-observer variability of the POCT results was compared among five clinical staff for 400 cases. RESULTS: Group 1: 1000 patients, 58.5% female, age 16-91, median age 57. Forty-one patients (4.1%) were diagnosed with CD. The sensitivities of the POCT, IgA-TTG, and IgA-EMA were 82.9, 78.1, and 70.7%; the specificities were 85.4, 96.3, and 99.8%. Group 2: 61 patients, 83% female; age 17-73, median age 35. The POCT had 100% sensitivity and negative predictive value in detecting CD in group 2. Most patients preferred the POCT to venepuncture (90.4% vs. 2.8%). There was good inter-observer agreement on the POCT results with a Fleiss Kappa coefficient of 0.895. CONCLUSIONS: The POCT had comparable sensitivities to serology, and correctly identified all CD cases in a gluten sensitive cohort. However, its low specificity may increase unnecessary investigations. Despite its advantage of convenience and rapid results, it may not add significant value to case finding in an office-based setting.

Metastatic Pancreatic Cancer: ASCO Clinical Practice Guideline Update.

Purpose In 2016, ASCO published a guideline to assist in clinical decision making in metastatic pancreatic cancer for initial assessment after diagnosis, first- and second-line treatment options, palliative and supportive care, and follow-up. The purpose of this update is to incorporate new evidence related to second-line therapy for patients who have experienced disease progression or intolerable toxicity during first-line therapy. Methods ASCO convened an Expert Panel to conduct a systematic review of the literature on second-line therapy published between June 2015 and January 2018. Recommendations on other topics covered in the 2016 Metastatic Pancreatic Cancer Guideline were endorsed by the Expert Panel. Results Two new studies were found that met the inclusion criteria. Recommendations For second-line therapy, gemcitabine plus nanoparticle albumin-bound paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin), an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1, and a favorable comorbidity profile; fluorouracil plus nanoliposomal irinotecan can be offered to patients with first-line treatment with gemcitabine plus NAB-paclitaxel, an ECOG PS of 0 to 1, and a favorable comorbidity profile; fluorouracil plus irinotecan or fluorouracil plus oxaliplatin may be offered when there is a lack of availability of fluorouracil plus nanoliposomal irinotecan; gemcitabine or fluorouracil should be offered to patients with either an ECOG PS of 2 or a comorbidity profile that precludes other regimens. Testing select patients for mismatch repair deficiency or microsatellite instability is recommended, and pembrolizumab is recommended for patients with mismatch repair deficiency or high microsatellite instability tumors. Endorsed recommendations from the 2016 version of this guideline for computed tomography, baseline performance status and comorbidity profile, defining goals of care, first-line therapy, and palliative care are also contained within the full guideline text. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .