An Observational Study on Cystic Alterations in Normal Dental Follicles Associated with Impacted Lower Third Molar for Early Intervention.

AIM: To evaluate the cystic changes in the radiographically normal dental follicle associated with impacted mandibular third molar. MATERIALS AND METHODS: This study was conducted on 80 patients. Samples were selected using a convenient sampling technique from the patients who had impacted mandibular third molars in Pell and Gregory's positions B and C, with follicular space less than 2.5 mm in diameter. After surgical removal of an impacted tooth, the dental follicle was sent for histopathologic evaluation. RESULTS: Pathologic alterations were found in 19% of cases out of 80 samples. Odontogenic keratocystic and dentigerous cystic changes were found in 7% of cases. A statistically significant cystic alteration was found in female patients and distoangular impacted teeth. CONCLUSION: This study shows a significant cystic alteration in the radiologically normal dental follicles. Clinical and radiographic features alone may not be a reliable indicator of the absence of pathology. Early intervention of impacted teeth will help to reduce morbidity due to the development of pathology. CLINICAL SIGNIFICANCE: This study will help educate patients on the risks of retaining impacted teeth, based on scientific facts, in order to minimize the risks and to assess the correlation of pathologic alterations with the depth of impaction and angular position of the impacted tooth.

Evaluating the Clinical Efficacy of Maxillary Labial Frenectomy Procedure Using Diode Laser (980 nm) and Conventional Scalpel: An Observational Study.

Aim: This is an era of minimally invasive and least traumatic surgical interventions being focused on. The traditional scalpel frenectomy technique offers an increase in post-operative sequelae. To unravel this scenario a comparative evaluation is carried out to find out the clinical outcomes and quality of life after maxillary labial frenectomy using a conventional scalpel and diode laser frenectomy of 980 nm. Materials and Methods: Thirty-six subjects age ranging between 18 and 45 years reported to the Department of Oral and Maxillofacial Surgery, MES Dental College, Perinthalmanna with an aberrant frenal attachment of maxillary labial frenum were randomly assigned into two groups. Group A underwent the conventional scalpel technique and group B for the diode laser-assisted (980 nm) frenectomy technique. The post-operative parameters of ooze from the surgical site, pain, wound healing, and discomfort or acceptance of the procedure were assessed on day 1, day 7, and day 14, respectively. Results: The diode laser group exhibited statistically significant clinical and healing outcomes. Less pain, minimal or absent ooze, increased healing, and better acceptance of the procedure with diode laser at 1, 7, and 14 days recall visit. Conclusion: Surgical interventions involving needle puncture and the associated post-operative sequelae are the most dreaded experiences that make patients indifferent toward surgical treatments. Thus in terms of better clinical outcomes and improved quality of life diode laser frenectomy is an excellent alternative wherein a needleless anesthetic success followed by minimal surgical intervention and less post-operative sequelae with fast recovery is possible.

ZEB1 loss increases glioma stem cell tumorigenicity and resistance to chemoradiation.

OBJECTIVE: Glioblastoma has been known to be resistant to chemotherapy and radiation, whereas the underlying mechanisms of resistance have not been fully elucidated. The authors studied the role of the transcription factor ZEB1 (zinc finger E-box-binding homeobox 1 protein), which is associated with epithelial-mesenchymal transition (EMT) and is central to the stemness of glioblastoma, to determine its role in therapeutic resistance to radiation and chemotherapy. The authors previously demonstrated that ZEB1 is deleted in a majority of glioblastomas. METHODS: The authors explored resistance to therapy in the context of ZEB1 loss and overexpression in glioma stem cells (GSCs) and in patient data. RESULTS: Patients with ZEB1 loss had a shorter survival time than patients with wild-type ZEB1 in both the high- and low-MGMT groups. Consistent with the clinical data, mice implanted with ZEB1 knockdown GSCs showed shortened survival compared with mice inoculated with nonsilencing control (NS) short-hairpin RNA (shRNA) GSC glioblastoma. ZEB1-deleted GSCs demonstrated increased tumorigenicity with regard to proliferation and invasion. Importantly, GSCs that lose ZEB1 expression develop enhanced resistance to chemotherapy, radiotherapy, and combined chemoradiation. ZEB1 loss may lead to increased HER3 expression through the HER3/Akt pathway associated with this chemoresistance. Conversely, overexpression of ZEB1 in GSCs that are ZEB1 null leads to increased sensitivity to chemoradiation. CONCLUSIONS: The study results indicate that ZEB1 loss in cancer stem cells confers resistance to chemoradiation and uncovers a potentially targetable cell surface receptor in these resistant cells.

Large Bilateral Compressible Neck Mass in 55-Year-Old Man.

A 55-year-old man with a medical history significant for hypertension, coronary artery disease, and obstructive sleep apnea presents with an enlarging neck mass of more than 2 years' duration. What is your diagnosis?

Risk of a subsequent diagnosis of inflammatory bowel disease in subjects with ophthalmic disorders associated with inflammatory bowel disease: a retrospective cohort analysis of UK primary care data.

OBJECTIVES: Ophthalmic conditions including anterior uveitis (AU), episcleritis and scleritis may occur in association with the inflammatory bowel diseases (IBD) as ophthalmic extraintestinal manifestations. The aim of this study was to assess the risk of a later IBD diagnosis in those presenting with IBD associated ocular inflammation (IAOI). DESIGN: Retrospective cohort study. SETTING: Primary care UK database. PARTICIPANTS: 38 805 subjects with an IAOI were identified (median age 51 (38-65), 57% women) and matched to 153 018 subjects without IAOI. MEASURES: The risk of a subsequent diagnosis of IBD in subjects with IAOIs compared with age/sex matched subjects without IAOI. HRs were adjusted for age, sex, body mass index, deprivation, comorbidity, smoking, baseline axial arthropathy, diarrhoea, loperamide prescription, anaemia, lower gastrointestinal bleeding and abdominal pain.Logistic regression was used to produce a prediction model for a diagnosis of IBD within 3 years of an AU diagnosis. RESULTS: 213 (0.6%) subsequent IBD diagnoses (102 ulcerative colitis (UC) and 111 Crohn's disease (CD)) were recorded in those with IAOIs and 329 (0.2%) (215 UC and 114 CD) in those without. Median time to IBD diagnosis was 882 (IQR 365-2043) days in those with IAOI and 1403 (IQR 623-2516) in those without. The adjusted HR for a subsequent diagnosis of IBD was 2.25 (95% CI 1.89 to 2.68), p<0.001; for UC 1.65 (95% CI 1.30 to 2.09), p<0.001; and for CD 3.37 (95% CI 2.59 to 4.40), p<0.001 in subjects with IAOI compared with those without.Within 3 years of an AU diagnosis, 84 (0.5%) subjects had a recorded diagnosis of IBD. The prediction model performed well with a C-statistic of 0.75 (95% CI 0.69 to 0.80). CONCLUSIONS: Subjects with IAOI have a twofold increased risk of a subsequent IBD diagnosis. Healthcare professionals should be alert for potential signs and symptoms of IBD in those presenting with ophthalmic conditions associated with IBD.

Paramassetric Subcutaneous Dirofilariasis: A Rare Entity.

Dirofilariasis is an uncommon zoonotic parasitic infection affecting humans due to the bite of a mosquito vector. It is an endemic caused by Dirofilaria which is characterized in humans as nodules in lungs, subcutaneous tissue, peritoneal cavity, eyes. We present a case of Dirofilariasis with subcutaneous presentation in paramassetric region.

The Risk of Later Diagnosis of Inflammatory Bowel Disease in Patients With Dermatological Disorders Associated With Inflammatory Bowel Disease.

BACKGROUND: Dermatological conditions such as erythema nodosum (EN), pyoderma gangrenosum, Sweet's syndrome, and aphthous stomatitis can occur with inflammatory bowel disease (IBD) and are considered dermatological extraintestinal manifestations (D-EIMs). Rarely, they may precede IBD. Other common conditions such as psoriasis have also been associated with IBD. This study examined the risk of a subsequent IBD diagnosis in patients presenting with a D-EIM. METHODS: A retrospective cohort study compared patients with D-EIMs and age-/sex-matched patients without D-EIMs. Hazard ratios (HRs) were adjusted for age, sex, body mass index, deprivation, comorbidity, smoking, loperamide use, anemia, and lower gastrointestinal symptoms. Logistic regression was used to produce a prediction model for the diagnosis of IBD within 3 years of EN diagnosis. RESULTS: We matched 7447 patients with D-EIMs (74% female; median age 38 years (interquartile ratio [IQR], 24-65 years) to 29,297 patients without D-EIMs. We observed 131 (1.8%) subsequent IBD diagnoses in patients with D-EIMs compared with 65 (0.2%) in those without D-EIMs. Median time to IBD diagnosis was 205 days (IQR, 44-661 days) in those with D-EIMs and 1594 days (IQR, 693-2841 days) in those without D-EIMs. The adjusted HR for a later diagnosis of IBD was 6.16 (95% confidence interval [CI], 4.53-8.37; P < 0.001), for ulcerative colitis the HR was 3.30 (95% CI, 1.98-5.53; P < 0.001), and for Crohn's disease the HR was 8.54 (95% CI, 5.74-12.70; P < 0.001). Patients with psoriasis had a 34% increased risk of a subsequent IBD diagnosis compared with the matched control patients (HR, 1.34; 95% CI, 1.20-1.51; P < 0.001). We included 4043 patients with an incident EN diagnosis in the prediction model cohort, with 87 patients (2.2%) diagnosed with IBD within 3 years. The model had a bias-corrected c-statistic of 0.82 (95% CI, 0.78-0.86). CONCLUSIONS: Patients with D-EIMs have a 6-fold increased risk of a later diagnosis of IBD. Younger age, smoking, low body mass index, anemia, and lower gastrointestinal symptoms were associated with an increased risk of diagnosis of IBD within 3 years in patients with EN.

Fibroblasts as immune regulators in infection, inflammation and cancer.

In chronic infection, inflammation and cancer, the tissue microenvironment controls how local immune cells behave, with tissue-resident fibroblasts emerging as a key cell type in regulating activation or suppression of an immune response. Fibroblasts are heterogeneous cells, encompassing functionally distinct populations, the phenotypes of which differ according to their tissue of origin and type of inciting disease. Their immunological properties are also diverse, ranging from the maintenance of a potent inflammatory environment in chronic inflammation to promoting immunosuppression in malignancy, and encapsulating and incarcerating infectious agents within tissues. In this Review, we compare the mechanisms by which fibroblasts control local immune responses, as well as the factors regulating their inflammatory and suppressive profiles, in different tissues and pathological settings. This cross-disease perspective highlights the importance of tissue context in determining fibroblast-immune cell interactions, as well as potential therapeutic avenues to exploit this knowledge for the benefit of patients with chronic infection, inflammation and cancer.

Elevated Asparagine Biosynthesis Drives Brain Tumor Stem Cell Metabolic Plasticity and Resistance to Oxidative Stress.

Asparagine synthetase (ASNS) is a gene on the long arm of chromosome 7 that is copy-number amplified in the majority of glioblastomas. ASNS copy-number amplification is associated with a significantly decreased survival. Using patient-derived glioma stem cells (GSC), we showed that significant metabolic alterations occur in gliomas when perturbing the expression of ASNS, which is not merely restricted to amino acid homeostasis. ASNS-high GSCs maintained a slower basal metabolic profile yet readily shifted to a greatly increased capacity for glycolysis and oxidative phosphorylation when needed. This led ASNS-high cells to a greater ability to proliferate and spread into brain tissue. Finally, we demonstrate that these changes confer resistance to cellular stress, notably oxidative stress, through adaptive redox homeostasis that led to radiotherapy resistance. Furthermore, ASNS overexpression led to modifications of the one-carbon metabolism to promote a more antioxidant tumor environment revealing a metabolic vulnerability that may be therapeutically exploited. IMPLICATIONS: This study reveals a new role for ASNS in metabolic control and redox homeostasis in glioma stem cells and proposes a new treatment strategy that attempts to exploit one vulnerable metabolic node within the larger multilayered tumor network.

Intimate Partner Violence and the Risk of Developing Fibromyalgia and Chronic Fatigue Syndrome.

Intimate partner violence (IPV) is a global public health issue with a variety of ill health consequences associated with exposure. Due to the stimulation of chronic stress and inflammatory pathways, childhood abuse has been associated with the subsequent development of functional syndromes such as fibromyalgia and chronic fatigue syndrome (CFS). Although IPV in women appears to elicit similar biochemical responses, this association has not been tested thoroughly in IPV survivors. These functional syndromes are complex in etiology and any indication of their risk factors would benefit health care professionals managing this population. Therefore, we aimed to investigate the association between exposure to IPV with functional syndromes: fibromyalgia and CFS. We conducted a retrospective open cohort study using "The Heath Improvement Network" database between January 1, 1995 and December 1, 2017. A total of 18,547 women who were exposed to IPV were each matched by age to four controls who were not exposed (n = 74,188). The main outcome measures were the risk of developing fibromyalgia and CFS. These were presented as adjusted incidence rate ratios (aIRR) with 95% confidence intervals (CIs). We found that 97 women in the exposed group developed fibromyalgia (incidence rate [IR] = 1.63 per 1,000 person-years) compared to 239 women in the unexposed group (IR = 0.83 per 1,000 person-years). Following adjustment, this translated to an IRR of 1.73 (95% CI = [1.36, 2.22]). Similarly, 19 women developed CFS in the exposed group (IR = 0.32 per 1,000 person-years), compared to 53 in the unexposed group (0.18 per 1,000 person-years), which translates to an aIRR of 1.92 (95% CI = [1.11, 3.33]). Therefore, we have identified an association between a history of IPV in women and the development of these functional syndromes, which may provide more information to inform the biopsychosocial pathway precipitating the development of fibromyalgia and CFS.

IER5, a DNA damage response gene, is required for Notch-mediated induction of squamous cell differentiation.

Notch signaling regulates squamous cell proliferation and differentiation and is frequently disrupted in squamous cell carcinomas, in which Notch is tumor suppressive. Here, we show that conditional activation of Notch in squamous cells activates a context-specific gene expression program through lineage-specific regulatory elements. Among direct Notch target genes are multiple DNA damage response genes, including IER5, which we show is required for Notch-induced differentiation of squamous carcinoma cells and TERT-immortalized keratinocytes. IER5 is epistatic to PPP2R2A, a gene that encodes the PP2A B55α subunit, which we show interacts with IER5 in cells and in purified systems. Thus, Notch and DNA-damage response pathways converge in squamous cells on common genes that promote differentiation, which may serve to eliminate damaged cells from the proliferative pool. We further propose that crosstalk involving Notch and PP2A enables tuning and integration of Notch signaling with other pathways that regulate squamous differentiation.

Changing patterns in the epidemiology and outcomes of inflammatory bowel disease in the United Kingdom: 2000-2018.

BACKGROUND: Data regarding incidence, prevalence and long-term outcomes of inflammatory bowel diseases in the UK are limited or outdated. AIMS: To investigate incidence and prevalence of Crohn's disease and ulcerative colitis and risk of colorectal cancer and all-cause mortality in these diseases. METHODS: Inflammatory bowel disease cases between 2000 and 2018 were identified from a national primary care database. Inflammatory bowel disease prevalence was forecast until 2025. The association between inflammatory bowel disease and colorectal cancer and all-cause mortality was investigated using age/sex-matched retrospective cohort studies. Hazard ratios were adjusted for age, sex, deprivation, comorbidity, smoking status and body mass index. RESULTS: Ulcerative colitis prevalence increased from 390 to 570 per 100 000 population from 2000 to 2017. Prevalence of Crohn's disease increased from 220 to 400 per 100 000. In 2017 male Crohn's disease prevalence was 0.35% (95% confidence interval 0.34-0.36); female prevalence was 0.44% (0.43-0.45). Prevalence of inflammatory bowel disease is predicted to be 1.1% by 2025. Incidence of ulcerative colitis and Crohn's disease was 23.2 (22.8-23.6) and 14.3 (14.0-14.7) per 100 000 person-years respectively. Subjects with ulcerative colitis were more likely to develop colorectal cancer than controls (adjusted Hazard Ratio 1.40 [1.23-1.59]). Colorectal cancer rates remained stable in inflammatory bowel diseases over time. Ulcerative colitis and Crohn's disease were associated with increased risk of all-cause mortality (1.17 [1.14-1.21] and 1.42 [1.36-1.48] respectively). CONCLUSIONS: The UK prevalence of inflammatory bowel disease is greater than previous reports suggest and we predict an 11% increase in prevalence by the year 2025. Mortality risk in inflammatory bowel disease and colorectal cancer risk in ulcerative colitis are increased compared to matched controls.

Mid-term follow-up after all-size acetabular revision and proposal for a stability classification system.

BACKGROUND: There is a trend for using jumbo cups/oblong devices for acetabular reconstruction as alternative to biological solutions. We report about a spectrum of reconstruction methods and their mid-term results. METHODS: Inclusion of 214 consecutive patients undergoing total hip arthroplasty revision surgery. Patients were examined using the Harris Hip Score (HHS). Based on the intraoperative acetabular defect situation, cases were classified into 1 of 5 possible categories of a stability classification for acetabular replacement (SCAR). RESULTS: Mean HHS improved from 42 preoperatively (range 12-62) to 77 (range 54-90; p < 0.05) 6 months after operation. There were significant differences of the pre-and postoperative HHS between SCAR subgroups (p < 0.05). Inter-observer reliability of the SCAR was high (kappa 0.94 (95% CI, 0.90-0.98)). Re-revision was performed in 15 cases (7%). CONCLUSION: The SCAR classification is a practicable tool for intraoperative decision-making as it provides standardised treatment recommendations.

The Outcomes of Emergency Admissions With Ulcerative Colitis Between 2007 and 2017 in England.

BACKGROUND AND AIMS: Patients with ulcerative colitis [UC] may present as emergencies and require rapid escalation of therapy. This study aimed to assess the mortality, colectomy, and readmission risks, during and following a first emergency admission with UC. METHODS: Using Hospital Episode Statistics, subjects aged between 18 and 60 years, coded with a first emergency admission with UC, were identified between 2007 and 2017. Influences of demographic factors, comorbidity, anti-tumour necrosis factor [TNF] therapy, and provider UC activity on mortality and colectomy were examined. RESULTS: A total of 10 051 subjects (46% female; median age 33 years [interquartile range [IQR] 25-44]) were identified. Mortality was 0.2% in hospital and 0.5% at 12 months and, following colectomy during acute admission, it was 1.4% in hospital and 2.1% at 12 months. Females had reduced risk of colectomy during admission: odds ratio [OR] 0.73 (95% confidence interval [CI] 0.62-0.85). Comparing the period 2007-2011 with 2012-2017, the rate of colectomy fell during acute admissions: OR 0.85 [0.72-0.99], p = 0.038 and at 12 months after admission: OR 0.73 [0.61-0.87]. Anti-TNF therapy increased 4-fold in acute UC admissions from 2007-2017. Those receiving anti-TNF therapy had a 70% increased risk of colectomy during index admission compared with those not receiving anti-TNF: OR 1.72 [1.29-2.31]. Increased time to colectomy during first admission was associated with female sex: hazard ratio [HR] 0.84 [0.72-0.98] and Asian ethnicity: HR 0.61 [0.44-0.85], whereas reduced time was associated with increased comorbidity, lower deprivation, and high provider volume of colectomies for UC: HR 1.59 [1.31-1.93]. CONCLUSIONS: Mortality following colectomy was 1.4% in hospital and 2.1% at 12 months, and no significant change over time was observed. Colectomy during emergency admission for UC was less common in females. Rates of anti-TNF therapy during emergency admission for UC have increased and overall colectomy rates have fallen. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Global smoking trends in inflammatory bowel disease: A systematic review of inception cohorts.

BACKGROUND AND AIMS: The effect of smoking on the risk of developing inflammatory bowel diseases (IBD) may be heterogeneous across ethnicity and geography. Although trends in smoking for the general population are well described, it is unknown whether these can be extrapolated to the IBD cohort. Smoking prevalence trends specific to the global IBD cohort over time have not been previously reported. This is a systematic review of smoking prevalence specific to the IBD cohort across geography. METHODS: A systematic literature search was conducted on Medline and Embase from January 1st 1946 to April 5th 2018 to identify population-based studies assessing the prevalence of smoking at diagnosis in inception cohorts of Crohn's disease(CD) or ulcerative colitis(UC). Studies that did not report smoking data from time of diagnosis or the year of IBD diagnosis were excluded. Prevalence of smoking in IBD was stratified by geography and across time. RESULTS: We identified 56 studies that were eligible for inclusion. Smoking prevalence data at diagnosis of CD and UC was collected from twenty and twenty-five countries respectively. Never-smokers in the newly diagnosed CD population in the West has increased over the last two decades, especially in the United Kingdom and Sweden; +26.6% and +11.2% respectively. Never-smokers at CD diagnosis in newly industrialised nations have decreased over the 1990s and 2000s; China (-19.36%). Never-smokers at UC diagnosis also decreased in China; -15.4%. The former-smoker population at UC diagnosis in China is expanding; 11%(1990-2006) to 34%(2011-2013). CONCLUSION: There has been a reduction in the prevalence of smoking in the IBD cohort in the West. This is not consistent globally. Although, smoking prevalence has decreased in the general population of newly industrialised nations, this remains an important risk factor with longer term outcomes awaiting translation in both UC and CD.

Review article: managing the adverse events caused by anti-TNF therapy in inflammatory bowel disease.

BACKGROUND: Biological therapy is currently widely used to treat IBD. Infliximab, adalimumab and golimumab are currently licensed anti-TNF therapies. Biosimilar anti-TNF monoclonal antibodies are increasingly used. Anti-TNF therapies are widely used and their adverse effects are well characterised, and may cause significant morbidity and mortality in a small proportion of exposed patients. Gastroenterologists need to understand the mechanisms for these effects, recognise these swiftly and manage such events appropriately. AIM: To cover the range of potential adverse reactions as a result of biologic therapy and specifically management of these events. METHODS: A Medline and Pubmed search was undertaken. Search terms included were "anti-TNF," "infliximab" or "adalimumab" or "golimumab" combined with the keywords "ulcerative colitis" or "Crohn's disease" or "inflammatory bowel disease" and then narrowed to articles containing the keywords "complications," "side effects" or "adverse events" or "safety profile." International guidelines were also reviewed where relevant. RESULTS: Adverse events discussed in this review include infusion reactions, blood disorders and infections (including bacterial, viral, fungal and opportunistic infections) as well as autoimmune, dermatological disorders, cardiac and neurological conditions. Malignancies including solid organ, haematological and those linked to viral disease are discussed. CONCLUSIONS: Anti-TNF therapy has wide-ranging effects on the immune system resulting in a spectrum of potential adverse events in a small proportion of patients. Research advances are improving the understanding, recognition and management of these adverse events.

Association between child maltreatment and central sensitivity syndromes: a systematic review protocol.

INTRODUCTION: A growing body of evidence is identifying the link between a history of child maltreatment and a variety of adverse health outcomes ultimately leading to significant social and healthcare burden. Initial work has identified a potential association between child maltreatment and the development of a selection of somatic and visceral central sensitivity syndromes: fibromyalgia, chronic fatigue syndrome, temporomandibular joint disorder, chronic lower back pain, chronic neck pain, chronic pelvic pain, interstitial cystitis, vulvodynia, chronic prostatitis, tension-type headache, migraine, myofascial pain syndrome, irritable bowel syndrome and restless legs syndrome. METHODS AND ANALYSIS: Primary electronic searches will be performed in the Embase, MEDLINE, PubMed, Scopus, PyscINFO, CINAHL and Cochrane Library databases and a number of Grey Literature sources including child protection and paediatric conference proceedings. Following independent screening of studies by two review authors, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses template will be used to aid extraction. A meta-analysis will be conducted on the included case-control and cohort studies. The Newcastle-Ottawa grading system will be used to assess the quality of included studies. Results will be expressed as pooled ORs for binary data and mean differences for continuous data. ETHICS AND DISSEMINATION: Ethics approval will not be required. The final results of the review and meta-analysis will be submitted for peer-review publication and also disseminated at relevant conference presentations. PROSPERO REGISTRATION NUMBER: CRD42018089258.

Incidence, morbidity and mortality of patients with achalasia in England: findings from a study of nationwide hospital and primary care data.

BACKGROUND: Achalasia is an uncommon condition characterised by failed lower oesophageal sphincter relaxation. Data regarding its incidence, prevalence, disease associations and long-term outcomes are very limited. METHODS: Hospital Episode Statistics (HES) include demographic and diagnostic data for all English hospital attendances. The Health Improvement Network (THIN) includes the primary care records of 4.5 million UK subjects, representative of national demographics. Both were searched for incident cases between 2006 and 2016 and THIN for prevalent cases. Subjects with achalasia in THIN were compared with age, sex, deprivation tand smoking status matched controls for important comorbidities and mortality. RESULTS: There were 10 509 and 711 new achalasia diagnoses identified in HES and THIN, respectively. The mean incidence per 100 000 people in HES was 1.99 (95% CI 1.87 to 2.11) and 1.53 (1.42 to 1.64) per 100 000 person-years in THIN. The prevalence in THIN was 27.1 (25.4 to 28.9) per 100 000 population. Incidence rate ratios (IRRs) were significantly higher in subjects with achalasia (n=2369) compared with controls (n=3865) for: oesophageal cancer (IRR 5.22 (95% CI: 1.88 to 14.45), p<0.001), aspiration pneumonia (13.38 (1.66 to 107.79), p=0.015), lower respiratory tract infection (1.33 (1.05 to 1.70), p=0.02) and mortality (1.33 (1.17 to 1.51), p<0.001). The median time from achalasia diagnosis to oesophageal cancer diagnosis was 15.5 (IQR 20.4) years. CONCLUSION: The incidence of achalasia is 1.99 per 100 000 population in secondary care data and 1.53 per 100 000 person-years in primary care data. Subjects with achalasia have an increased incidence of oesophageal cancer, aspiration pneumonia, lower respiratory tract infections and higher mortality. Clinicians treating patients with achalasia should be made aware of these associated morbidities and its increased mortality.