Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19.

SARS-CoV-2 infection can cause severe respiratory COVID-19. However, many individuals present with isolated upper respiratory symptoms, suggesting potential to constrain viral pathology to the nasopharynx. Which cells SARS-CoV-2 primarily targets and how infection influences the respiratory epithelium remains incompletely understood. We performed scRNA-seq on nasopharyngeal swabs from 58 healthy and COVID-19 participants. During COVID-19, we observe expansion of secretory, loss of ciliated, and epithelial cell repopulation via deuterosomal cell expansion. In mild and moderate COVID-19, epithelial cells express anti-viral/interferon-responsive genes, while cells in severe COVID-19 have muted anti-viral responses despite equivalent viral loads. SARS-CoV-2 RNA+ host-target cells are highly heterogenous, including developing ciliated, interferon-responsive ciliated, AZGP1high goblet, and KRT13+ "hillock"-like cells, and we identify genes associated with susceptibility, resistance, or infection response. Our study defines protective and detrimental responses to SARS-CoV-2, the direct viral targets of infection, and suggests that failed nasal epithelial anti-viral immunity may underlie and precede severe COVID-19.

Factors Associated with Delays in Initiating Biologic Therapy in Patients with Inflammatory Bowel Disease.

INTRODUCTION: Expeditious initiation of biologic therapy is important in patients with inflammatory bowel disease (IBD). However, initiation of biologics in the outpatient setting may be delayed by various clinical, social, and financial variables. AIM: To evaluate the delay in initiation of an advanced therapy in IBD and to identify factors that contributed to this delay. METHODS: This was a multi-center retrospective study. Outpatients who were initiated on a biologic therapy from 3/1/2019 to 9/30/20 were eligible for the study. Univariate and multivariate linear regression analyses were performed to identify variables associated with a delay in biologic treatment initiation. Delay was defined as the days from decision date (prescription placement) to first infusion or delivery of medication. RESULTS: In total 411 patients (Crohn's disease, n = 276; ulcerative colitis, n = 129) were included in the analysis. The median [interquartile range-(IQR)] delay for all drugs was 20 [12-37] days (infliximab, 19 [13-33] days; adalimumab, 10 [5-26] days; vedolizumab, 21 [14-42] days; and ustekinumab, 21 [14-42] days). Multivariate linear regression analysis identified that the most important variables associated with delays in biologic treatment initiation was self-identification as Black, longer distance from treatment site, and lack of initial insurance coverage approval. CONCLUSION: There may be a significant delay in biologic treatment initiation in patients with IBD. The most important variables associated with this delay included self-identification as Black, longer distance from site, and lack of initial insurance coverage approval.

Opposite perceptual biases in analogous auditory and visual tasks are unique to consonant-vowel strings and are unlikely a consequence of repetition.

Despite wide reporting of a right ear (RE) advantage on dichotic listening tasks and a right visual field (RVF) advantage on visual half-field tasks, we know very little about the relationship between these perceptual biases. Previous studies that have investigated perceptual asymmetries for analogous auditory and visual consonant-vowel tasks have indicated a serendipitous finding: a RE advantage and a left visual field (LVF) advantage with poor cross-modal correlations. In this study, we examined the possibility that this LVF advantage for visual processing of consonant-vowel strings may be a consequence of repetition by examining perceptual biases in analogous auditory and visual tasks for both consonant-vowel strings and words. We replicated opposite perceptual biases for consonant-vowel strings (RE and LVF advantages). This did not extend to word stimuli where we found RE and RVF advantages. Furthermore, these perceptual biases did not differ across the three experimental blocks. Thus, we can firmly conclude that this LVF advantage is unique to consonant-vowel strings and is not a consequence of the repetition of a relatively limited number of stimuli. Finally, a test of covariances indicated no cross-modal relationships between laterality indices suggesting that perceptual biases are dissociable within individuals and cluster on mode of presentation.

Testing the relationship between lateralization on sequence-based motor tasks and language laterality using an online battery.

ABSTRACTStudies have highlighted an association between motor laterality and speech production laterality. It is thought that common demands for sequential processing may underlie this association. However, most studies in this area have relied on relatively small samples and have infrequently explored the reliability of the tools used to assess lateralization. We, therefore, established the validity and reliability of an online battery measuring sequence-based motor laterality and language laterality before exploring the associations between laterality indices on language and motor tasks. The online battery was completed by 621 participants, 52 of whom returned to complete the battery a second time. The three motor tasks included in the battery showed good between-session reliability (r ≥ .78) and were lateralized in concordance with hand preference. The novel measure of speech production laterality was left lateralized at population level as predicted, but reliability was less satisfactory (r = .62). We found no evidence of an association between sequence-based motor laterality and language laterality. Those with a left-hand preference were more strongly lateralized on motor tasks requiring midline crossing; this effect was not observed in right-handers. We conclude that there is little evidence of the co-lateralization of language and sequence-based motor skill on this battery.

Epigenetics: a catalyst of plant immunity against pathogens.

The plant immune system protects against pests and diseases. The recognition of stress-related molecular patterns triggers localised immune responses, which are often followed by longer-lasting systemic priming and/or up-regulation of defences. In some cases, this induced resistance (IR) can be transmitted to following generations. Such transgenerational IR is gradually reversed in the absence of stress at a rate that is proportional to the severity of disease experienced in previous generations. This review outlines the mechanisms by which epigenetic responses to pathogen infection shape the plant immune system across expanding time scales. We review the cis- and trans-acting mechanisms by which stress-inducible epigenetic changes at transposable elements (TEs) regulate genome-wide defence gene expression and draw particular attention to one regulatory model that is supported by recent evidence about the function of AGO1 and H2A.Z in transcriptional control of defence genes. Additionally, we explore how stress-induced mobilisation of epigenetically controlled TEs acts as a catalyst of Darwinian evolution by generating (epi)genetic diversity at environmentally responsive genes. This raises questions about the long-term evolutionary consequences of stress-induced diversification of the plant immune system in relation to the long-held dichotomy between Darwinian and Lamarckian evolution.

Increased ACE2 Levels and Mortality Risk of Patients With COVID-19 on Proton Pump Inhibitor Therapy.

INTRODUCTION: Proton pump inhibitor (PPI) use was recently reported to be associated with increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and worse clinical outcomes. The underlying mechanism(s) for this association are unclear. METHODS: We performed a prospective study of hospitalized coronavirus disease 2019 (COVID-19) patients and COVID-negative controls to understand how PPI use may affect angiotensin-converting enzyme 2 (ACE2) expression and stool SARS-CoV-2 RNA. Analysis of a retrospective cohort of hospitalized patients with COVID-19 from March 15, 2020 to August 15, 2020 in 6 hospitals was performed to evaluate the association of PPI use and mortality. Covariates with clinical relevance to COVID-19 outcomes were included to determine predictors of in-hospital mortality. RESULTS: Control PPI users had higher salivary ACE2 mRNA levels than nonusers, 2.39 ± 1.15 vs 1.22 ± 0.92 (P = 0.02), respectively. Salivary ACE2 levels and stool SARS-CoV-2 RNA detection rates were comparable between users and nonusers of PPI. In 694 hospitalized patients with COVID-19 (age = 58 years, 46% men, and 65% black), mortality rate in PPI users and nonusers was 30% (68/227) vs 12.1% (53/439), respectively. Predictors of mortality by logistic regression were PPI use (adjusted odds ratio [aOR] = 2.72, P < 0.001), age (aOR = 1.66 per decade, P < 0.001), race (aOR = 3.03, P = 0.002), cancer (aOR = 2.22, P = 0.008), and diabetes (aOR = 1.95, P = 0.003). The PPI-associated mortality risk was higher in black patients (aOR = 4.16, 95% confidence interval: 2.28-7.59) than others (aOR = 1.62, 95% confidence interval: 0.82-3.19, P = 0.04 for interaction). DISCUSSION: COVID-negative PPI users had higher salivary ACE2 expression. PPI use was associated with increased mortality risk in patients with COVID-19, particularly African Americans.

Assessing the reliability of an online behavioural laterality battery: A pre-registered study.

Studies of cerebral lateralization often involve participants completing a series of perceptual tasks under laboratory conditions. This has constrained the number of participants recruited in such studies. Online testing can allow for much larger sample sizes but limits the amount of experimental control that is feasible. Here we considered whether online testing could give valid and reliable results on four tasks: a rhyme decision visual half-field task, a dichotic listening task, a chimeric faces task, and a finger tapping task. We recruited 392 participants, oversampling left-handers, who completed the battery twice. Three of the tasks showed evidence of both validity and reliability, insofar as they showed hemispheric advantages in the expected direction and test-retest reliability of at least r = .75. The reliability of the rhyme decision task was less satisfactory (r = .62). We also confirmed a prediction that extreme left-handers were more likely to depart from typical lateralization. Lateralization across the two language tasks (dichotic listening and rhyme judgement) was weakly correlated, but unrelated to lateralization on the chimeric faces task. We conclude that three of the tasks, dichotic listening, chimeric faces and finger tapping, show considerable promise for online evaluation of cerebral lateralization.

Undersweep fixations during reading in adults and children.

Return sweeps take a reader's fixation from the end of one line to the start of the next. Return sweeps frequently undershoot their target and are followed by a corrective saccade toward the left margin. The pauses prior to corrective saccades are typically considered to be uninvolved in linguistic processing. However, recent findings indicate that these undersweep fixations influence skilled adult readers' subsequent reading pass across the line and provide preview of line-initial words. The current research examined these effects in children. First, a children's reading corpus analysis revealed that words receiving an undersweep fixation were more likely skipped and received shorter gaze durations during a subsequent pass. Second, a novel eye movement experiment that directly compared adults' and children's eye movements indicated that, during an undersweep fixation, readers very briefly allocate their attention to the fixated word-as indicated by inhibition of return effects during a subsequent pass-prior to deploying attention toward the line-initial word. We argue that prior to the redeployment of attention, readers extract information at the point of fixation that facilitates later encoding and saccade targeting. Given similar patterns of results for adults and children, we conclude that the mechanisms controlling for oculomotor coordination and attention necessary for reading across line boundaries are established from a very early point in reading development.

Binocular coordination and return-sweep saccades among skilled adult readers.

During reading, binocular coordination ensures that a unified perceptual representation of the text is maintained across eye movements. However, slight vergence errors exist. The magnitude of disparity at fixation onset is related to the length of the preceding saccade. Return-sweeps are saccadic eye movements that span a line of text and direct gaze from the end of one line to the start of the next. As these eye movements travel much farther than intraline saccades, increased binocular disparity following a return-sweep is likely. Indeed, increased disparity has been a proposed explanation for longer line-initial fixations. Thus, we sought to address the following questions: Is binocular disparity larger following a return-sweep saccade than it is following an intraline saccade, and is the duration of a line-initial fixation related to binocular disparity and coordination processes? To examine these questions, we recorded binocular eye movements as participants read multiline texts. We report that, following return-sweeps, the magnitude of disparity at fixation onset is increased. However, this increased magnitude of disparity is unrelated to the duration of line-initial fixations. We argue that longer line-initial fixations result from a lack of parafoveal preview for words at the start of the line.

Triple combination antibiotic therapy for carbapenemase-producing Klebsiella pneumoniae: a systematic review.

BACKGROUND: The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections. METHODS: The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2. RESULTS: Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients). CONCLUSIONS: Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.

Development and validation of case-finding algorithms for the identification of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis in large healthcare administrative databases.

PURPOSE: The aim of this study was to develop and validate case-finding algorithms for granulomatosis with polyangiitis (Wegener's, GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (Churg-Strauss, EGPA). METHODS: Two hundred fifty patients per disease were randomly selected from two large healthcare systems using the International Classification of Diseases version 9 (ICD9) codes for GPA/EGPA (446.4) and MPA (446.0). Sixteen case-finding algorithms were constructed using a combination of ICD9 code, encounter type (inpatient or outpatient), physician specialty, use of immunosuppressive medications, and the anti-neutrophil cytoplasmic antibody type. Algorithms with the highest average positive predictive value (PPV) were validated in a third healthcare system. RESULTS: An algorithm excluding patients with eosinophilia or asthma and including the encounter type and physician specialty had the highest PPV for GPA (92.4%). An algorithm including patients with eosinophilia and asthma and the physician specialty had the highest PPV for EGPA (100%). An algorithm including patients with one of the diagnoses (alveolar hemorrhage, interstitial lung disease, glomerulonephritis, and acute or chronic kidney disease), encounter type, physician specialty, and immunosuppressive medications had the highest PPV for MPA (76.2%). When validated in a third healthcare system, these algorithms had high PPV (85.9% for GPA, 85.7% for EGPA, and 61.5% for MPA). Adding the anti-neutrophil cytoplasmic antibody type increased the PPV to 94.4%, 100%, and 81.2% for GPA, EGPA, and MPA, respectively. CONCLUSION: Case-finding algorithms accurately identify patients with GPA, EGPA, and MPA in administrative databases. These algorithms can be used to assemble population-based cohorts and facilitate future research in epidemiology, drug safety, and comparative effectiveness. Copyright © 2016 John Wiley & Sons, Ltd.

Functional reconstruction of large medial canthal defects.

The aim of this study is to describe a surgical technique for the reconstruction of large medial canthal defects involving the lacrimal apparatus following excision of medial canthal tumors. Many different techniques for constructing a neopassage from the lacrimal sac to the nasal sinuses have been investigated and described in the literature. However, there continues to be difficulty with successful functional reconstruction of the lacrimal outflow tract without the long-term use of an indwelling tube. We herein describe a technique utilizing a paramedian forehead flap combined with AlloDerm (LifeCell Corporation, Township of Branchburg, NJ) as the conduit for reconstruction of the medial canthus and lacrimal outflow tract. We present a case series of three patients successfully reconstructed with the above technique and describe their presentation, treatment, and postoperative course. We provide a detailed description of the surgical technique and document the success of the technique in regard to patency and postprocedure function of the lacrimal conduit.

Flexible letter-position coding in Chinese-English L2 bilinguals: Evidence from eye movements.

Theories suggest that efficient recognition of English words depends on flexible letter-position coding, demonstrated by the fact that transposed-letter primes (e.g., JUGDE-judge) facilitate written word recognition more than substituted-letter primes (e.g., JUFBE-judge). The multiple route model predicts that reading experience should drive more flexible letter-position coding as readers transition from decoding words letter-by-letter to recognising words as wholes. This study therefore examined whether letter-position is coded flexibly in second-language English sentence reading for native Chinese speakers, and if this is influenced by English proficiency. Eye movements were measured while 54 adult native Chinese speakers read English sentences including either a real word (e.g., cheaply), a transposed-letter nonword (e.g., "chepaly"), or a substituted-letter nonword (e.g., "chegely"). Flexible letter-position coding was observed in initial and later processing stages-reading times were longer for substituted-letter than transposed-letter nonwords. In addition, reading times were longer in both initial and later processing stages for transposed-letter nonwords than real words, indicating that, despite encoding letter-position flexibly, readers processed letter-position. Although pre-registered frequentist analyses suggested that English proficiency did not predict overall reading times, Bayes Factors indicated that there was evidence for such a relationship. It is therefore likely that this proficiency analysis suffered from low power. Finally, neither frequentist nor Bayes Factor analyses suggested that English proficiency influenced the difference in reading times between different target word types, i.e., the nature of letter-position coding. Overall, these results suggest that highly proficient L2 learners code letter-position flexibly.

Communicative capital: a key resource for human-machine shared agency and collaborative capacity.

In this work, we present a perspective on the role machine intelligence can play in supporting human abilities. In particular, we consider research in rehabilitation technologies such as prosthetic devices, as this domain requires tight coupling between human and machine. Taking an agent-based view of such devices, we propose that human-machine collaborations have a capacity to perform tasks which is a result of the combined agency of the human and the machine. We introduce communicative capital as a resource developed by a human and a machine working together in ongoing interactions. Development of this resource enables the partnership to eventually perform tasks at a capacity greater than either individual could achieve alone. We then examine the benefits and challenges of increasing the agency of prostheses by surveying literature which demonstrates that building communicative resources enables more complex, task-directed interactions. The viewpoint developed in this article extends current thinking on how best to support the functional use of increasingly complex prostheses, and establishes insight toward creating more fruitful interactions between humans and supportive, assistive, and augmentative technologies.

Can we shift belief in the 'Law of Small Numbers'?

'Sample size neglect' is a tendency to underestimate how the variability of mean estimates changes with sample size. We studied 100 participants, from science or social science backgrounds, to test whether a training task showing different-sized samples of data points (the 'beeswarm' task) can help overcome this bias. Ability to judge if two samples came from the same population improved with training, and 38% of participants reported that they had learned to wait for larger samples before making a response. Before and after training, participants completed a 12-item estimation quiz, including items testing sample size neglect (S-items). Bonus payments were given for correct responses. The quiz confirmed sample size neglect: 20% of participants scored zero on S-items, and only two participants achieved more than 4/6 items correct. Performance on the quiz did not improve after training, regardless of how much learning had occurred on the beeswarm task. Error patterns on the quiz were generally consistent with expectation, though there were some intriguing exceptions that could not readily be explained by sample size neglect. We suggest that training with simulated data might need to be accompanied by explicit instruction to be effective in counteracting sample size neglect more generally.

Orthographic neighborhood effects during lateralized lexical decision are abolished with bilateral presentation.

Words presented to the right visual field (RVF) are processed more rapidly than those in the left visual field (LVF), presumably because of more direct links to the language dominant left cerebral hemisphere. This effect is moderated by a word's orthographic neighborhood size (N), with LVF facilitation and RVF inhibition for words with a large N. Across two experiments, we sought to further examine lateralized N effects. Experiment 1 examined how hemispheric dominance for language influenced lateralized N effects, in 140 left-handers using a visual half-field task with bilateral presentation. Neither participants with a right ear advantage on a dichotic listening task nor participants with no right ear advantage showed the expected N effect, making the results ambiguous: it could be that left-handers fail to show N effects, or the effect could be abolished by some procedural aspect. Experiment 2 looked to test these options by testing 56 right-handers who responded to the same stimulus set under the original bilateral presentation condition and under unilateral presentation. N effects were found under unilateral but not bilateral presentation. We had adopted bilateral presentation because it had been recommended as better than unilateral presentation for controlling fixation and visual stimulation; our results indicate that this is not a minor methodological modification: it can dramatically affect lateralized N effects. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Impedance Planimetry and the Changing Paradigm of Esophageal Dysphagia.

OBJECTIVES: Patients presenting with dysphagia can encounter a pathway to therapy and relief that is expensive and frustrating. High resolution impedance planimetry (HRIP) is a new mechanism for enhancing and possibly hastening that process. A balloon with integrated pressure sensors is utilized to measure luminal geometry and pressure by volume-controlled distention. Esophagogastric junction (EGJ) distensibility and body contractility are assessed at the time of other endoscopic procedures. Here we describe a single-center experience utilizing HRIP in the endoscopic evaluation of patients presenting with dysphagia. METHODS: A prospectively maintained registry of patients undergoing impedance planimetry assessments at an academic medical center was queried for demographics, procedural details, and patient-reported outcomes. RESULTS: Data was reviewed for 122 procedures performed by two providers. HRIP was performed in 63 (52%) patients for initial dysphagia assessment, 36 (30%) for follow-up assessment, and 20 (16%) as a procedural adjunct at the time of other planned procedures. HRIP contractile response was characterized as normal in 36%, absent in 32%, and diminished/disorganized in 14%. These results motivated clinical planning for surgical referral in 7 (5%) patients, 31 (26%) additional testing, and 82 (68%) continued medical management and follow-up. DISCUSSION: HRIP is an emerging endoscopic modality which can streamline diagnostic work-up and therapeutic planning for patients with symptomatic dysphagia. Using functional esophageal assessment at the time of other diagnostic and therapeutic procedures, HRIP may expedite care and lead to improved patient satisfaction and clinical outcomes.

Inconsistent language lateralisation - Testing the dissociable language laterality hypothesis using behaviour and lateralised cerebral blood flow.

BACKGROUND: Most people have strong left-brain lateralisation for language, with a minority showing right- or bilateral language representation. On some receptive language tasks, however, lateralisation appears to be reduced or absent. This contrasting pattern raises the question of whether and how language laterality may fractionate within individuals. Building on our prior work, we postulated (a) that there can be dissociations in lateralisation of different components of language, and (b) these would be more common in left-handers. A subsidiary hypothesis was that laterality indices will cluster according to two underlying factors corresponding to whether they involve generation of words or sentences, versus receptive language. METHODS: We tested these predictions in two stages: At Step 1 an online laterality battery (Dichotic listening, Rhyme Decision and Word Comprehension) was given to 621 individuals (56% left-handers); At Step 2, functional transcranial Doppler ultrasound (fTCD) was used with 230 of these individuals (51% left-handers). 108 left-handers and 101 right-handers gave useable data on a battery of three language generation and three receptive language tasks. RESULTS: Neither the online nor fTCD measures supported the notion of a single language laterality factor. In general, for both online and fTCD measures, tests of language generation were left-lateralised. In contrast, the receptive tasks were at best weakly left-lateralised or, in the case of Word Comprehension, slightly right-lateralised. The online measures were only weakly correlated, if at all, with fTCD measures. Most of the fTCD measures had split-half reliabilities of at least .7, and showed a distinctive pattern of intercorrelation, supporting a modified two-factor model in which Phonological Decision (generation) and Sentence Decision (reception) loaded on both factors. The same factor structure fitted data from left- and right-handers, but mean scores on the two factors were lower (less left-lateralised) in left-handers. CONCLUSIONS: There are at least two factors influencing language lateralization in individuals, but they do not correspond neatly to language generation and comprehension. Future fMRI studies could help clarify how far they reflect activity in specific brain regions.

Spelling ability influences early letter encoding during reading: Evidence from return-sweep eye movements.

In recent years, there has been an increase in research concerning individual differences in readers' eye movements. However, this body of work is almost exclusively concerned with the reading of single-line texts. While spelling and reading ability have been reported to influence saccade targeting and fixation times during intra-line reading, where upcoming words are available for parafoveal processing, it is unclear how these variables affect fixations adjacent to return-sweeps. We, therefore, examined the influence of spelling and reading ability on return-sweep and corrective saccade parameters for 120 participants engaged in multiline text reading. Less-skilled readers and spellers tended to launch their return-sweeps closer to the end of the line, prefer a viewing location closer to the start of the next, and made more return-sweep undershoot errors. We additionally report several skill-related differences in readers' fixation durations across multiline texts. Reading ability influenced all fixations except those resulting from return-sweep error. In contrast, spelling ability influenced only those fixations following accurate return-sweeps-where parafoveal processing was not possible prior to fixation. This stands in contrasts to an established body of work where fixation durations are related to reading but not spelling ability. These results indicate that lexical quality shapes the rate at which readers access meaning from the text by enhancing early letter encoding, and influences saccade targeting even in the absence of parafoveal target information.

A Spy took a bite to get the diagnosis right: the benefit of SpyGlass technology in the diagnosis of autoimmune pancreatitis evading traditional diagnostic methods.

Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis that is often overlooked and is usually characterised clinically by frequent presentations with obstructive jaundice. Serum IgG4 testing as a means to 'rule out' IgG4-related disease may not be as helpful as initially thought and may lead to a missed diagnosis if suspicion is low. We present a patient with a years long history of recurrent pancreatitis ultimately found to have AIP after undergoing evaluation with a relatively new technology, SpyGlass, which allows for direct cholangioscopy and enabled us to make the correct diagnosis.