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Maxillofacial fractures are one of the common presentations in an emergency department. They are considered to be one of the significant and dominant conditions that requires treatment as the fractures can result in morbidity, mortality, psychological, functional disability, and facial mutilation. The incidence, patterns, and etiology of maxillofacial fractures vary from one country to another due to the geographical, cultural, social, and economic differences. The present study included 176 patients from January 2019 to September 2020 that aimed to evaluate the pattern of maxillofacial fractures and to learn the etiology for the same.

Background and Aims: Antiplatelet dugs are often interrupted preceding invasive dental extraction because of concern of bleeding complications. The fear of uncontrolled bleeding often prompts medical and dental practitioners to stop aspirin intake for 7 to 10 days before any surgical procedure, which puts the patient at risk from adverse thrombotic events. The aim of the study conducted was to evaluate the bleeding pattern after routine dental extraction among patients on low dose long term aspirin therapy. Methods: A total of 104 subjects in the age group of 30-65 years, who continued to have aspirin intake during extraction were included in the study. Dental extraction was performed without stopping aspirin therapy under local anesthesia. The post-operative blood loss was quantified by weighing the gauze pre and post operatively and adding total volume of fluid in the suction jar. Results: Of these 104 patients treated, 87% of patients had mild bleeding (

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.

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Data regarding incidence, prevalence and long-term outcomes of inflammatory bowel diseases in the UK are limited or outdated.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.

Background Microcystic adnexal carcinoma (MAC) is a rare, locally invasive skin neoplasm most commonly in the head and neck. MAC is routinely treated surgically and scant data is available regarding the role of definitive chemoradiotherapy (chemoRT) as a surgical alternative. Methods A single case of MAC treated with upfront chemoRT is presented along with a review of the literature. Results A 73-year old man with locally advanced MAC of the philtrum and nose declined surgery and was treated with concurrent intensity-modulated RT (70Gy) and paclitaxel/carboplatin. His tumor responded clinically within two weeks of treatment. Partial radiographic response was observed at three months with improvement up to one year post-treatment. He remains asymptomatic and progression-free six years from the completion of his treatment. Conclusion Definitive chemoRT may be a nonsurgical treatment alternative for MAC when surgery is not possible or declined.

Objectives The epidemiology of Behçet’s disease (BD) has not been well characterized in the UK. Evidence on the risk of cardiovascular disease, thromboembolic disease and mortality in patients with BD compared with the general population is scarce. Methods We used a large UK primary care database to investigate the epidemiology of BD. A retrospective matched cohort study was used to assess the following outcomes: risk of cardiovascular, thromboembolic disease and mortality. Controls were selected at a 1:4 ratio (age and gender matched). Cox proportional hazard models were used to derive adjusted hazard ratios (aHR). Results The prevalence of BD was 14.61 (95% CI 13.35–15.88) per 100 000 population in 2017. A total of 1281 patients with BD were compared with 5124 age- and gender-matched controls. There was significantly increased risk of ischaemic heart disease [aHR 3.09 (1.28–7.44)], venous thrombosis [aHR 4.80 (2.42–9.54)] and mortality [aHR 1.40 (1.07–1.84)] in patients with BD compared with corresponding controls. Patients with BD were at higher risk of pulmonary embolism compared with corresponding controls at baseline [adjusted odds ratio 4.64 (2.66–8.09), P < 0.0001]. The majority of patients with pulmonary embolism and a diagnosis of BD had pulmonary embolism preceding the diagnosis of BD, not after (87.5%; n = 28/32). Conclusion BD has a higher prevalence than previously thought. Physicians should be aware of the increased risk of developing ischaemic heart disease, stroke/transient ischaemic attack and deep venous thrombosis in patients with BD at an earlier age compared with the general population. Risk of embolism in patients with BD might vary across the disease course.

Acute suprarenal aortic occlusion, though rarely reported carries a high morbidity and mortality. Renal ischemia is one of the usual presenting features. Limb salvage and renal preservation depend on prompt diagnosis and management. A young patient with acute suprarenal aortic occlusion having renal failure and limb ischemia was managed with suprarenal thrombectomy and aortobifemoral bypass at our centre. Even though the presentation was delayed, renal functions were restored post procedure. This case highlights that renal revascularisation can be attempted in select cases with delayed presentation.

Summary Background Childhood maltreatment is a global public health, human rights, and moral issue that is associated with a substantial mental health burden. We aimed to assess the association between childhood maltreatment and the development of mental ill health and the initiation of new prescriptions for mental ill health. Methods In this population-based, retrospective, open cohort study, we used a dataset from individuals in The Health Improvement Network (THIN) database. THIN database comprises UK electronic medical records taken from 787 general practices throughout the UK. We used read codes in these records to identify exposed patients (those with a read code identifying officially confirmed childhood maltreatment or a maltreatment-related concern) and up to two unexposed patients (those without such read codes) from the same general practice, who were matched by age and sex. We evaluated the risk of developing depression, anxiety, or serious mental illness (a composite mental ill health outcome) or initiation of a prescription drug used to treat mental ill health, and the odds ratio of these events at baseline, in the exposed versus unexposed patients. Findings The first possible date for cohort entry (the study start date) was Jan 1, 1995, and patients could enter the cohort until the study end date, Dec 31, 2018. During the study period, 11 831 850 patients were eligible to participate. Of these patients, we identified 217 758 (1·8%) patients with any recorded childhood maltreatment. These patients were matched to 423 410 unexposed control patients with no recorded exposure to childhood maltreatment. The exposed group were followed up for a median of 1·8 years (IQR 0·6–4·3) versus 3·2 years (1·3–6·1) in the unexposed group. During the study period, 11 665 (5·9%) new diagnoses of mental ill health were made in the exposed group, giving an incidence rate of 16·8 events per 1000 person-years versus 15 301 (3·7%) new recorded diagnoses at an incidence rate of 8·3 events per 1000 person-years in the unexposed cohort, giving an adjusted IRR of 2·14 (95% CI 2·08–2·19). 30 911 (14·8%) patients in the exposed group received a new prescription for any type of mental ill health (incidence rate 46·5 events per 1000 person-years) versus 36 390 (8·9%) patients in the unexposed group (20·5 per 1000 person-years) resulting in an adjusted IRR of 2·44 (95% CI 2·40–2·48). Interpretation Childhood maltreatment is thought to affect one in three children globally; therefore, a doubled risk of developing mental ill health among these individuals represents a substantial contribution to the mental ill health burden in the UK. It is imperative that public health approaches, including those aimed at preventing and detecting childhood maltreatment and its associated negative consequences, are implemented to prevent mental ill health. Funding None.

Objective\ud To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics.\ud \ud Methods\ud We performed a propensity score–matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality.\ud \ud Results\ud During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score–matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62–1.10) and 0.79 (95% CI 0.57–1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75–1.27) and 0.85 (95% CI 0.61–1.20), respectively. There was no effect modification by age or sex.\ud \ud Conclusion\ud No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.

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. Fibroblasts are not just crucial structural cells; they exist as multiple functionally diverse populations, defined by their location and context, and regulate tissue immunity. Here, the authors review the immunological properties of fibroblasts, comprising both pro-inflammatory and immunosuppressive activities, in different tissues and disease states.

Introduction Skin diseases including erythema nodosum (EN), pyoderma gangrenosum (PG), Sweet’s syndrome (SS) and aphthous stomatitis (AS) can occur with inflammatory bowel disease (IBD). We examined the risk of later developing IBD in these skin disorders and the time to IBD diagnosis. Methods A large UK primary care database was examined between 1995–2018. Cases of EN (excluding sulfasalazine history), PG and all skin disorders associated with IBD combined were matched to controls on age, sex and GP registration. Pre-existing IBD cases were excluded. Subjects were followed until a diagnosis of ulcerative colitis (UC) or Crohn’s disease (CD) and incident rate ratio (IRR) modelled, adjusting for age, sex, body mass index, comorbidity, deprivation level and smoking status. The time to a later diagnosis of IBD in cases and controls was compared using the Mann-Whitney U test. Results 5,349 EN cases (median age 36 (IQR 23–51), 78% female) were matched to 21,100 controls. Median time to UC diagnosis was reduced in EN compared to control subjects (224 and 1,856 days respectively p 863 PG cases (age 57 (39–73), 40% male) were matched to 3,404 controls. Few IBD diagnoses were made during the study period (16 in PG cases and 6 in controls). Time to IBD diagnosis in PG cases was reduced compared to controls p=0.047. The rate of IBD was 13-fold that of controls (13.21 (5.07–34.41) p When skin disorders combined (EN, PG, SS and AS) were examined, 7,340 cases (median age 36 (23–50), female 74%) were matched to 21,764 controls. 133 cases of IBD were observed in the skin disorder group compared to 53 in controls. The rate of UC was more than 3-fold higher in the skin disorder group (3.63 (2.17–6.08) p Conclusions Skin disorders associated with IBD are not unique to IBD and clinicians who diagnose these conditions may not consider IBD leading to a delayed diagnosis. The relative risk of IBD is high in such skin disorders and symptoms suggestive of IBD should be sought, and screening investigations and gastroenterology referral considered.

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.

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, includingIER5, which we show is required for Notch-induced differentiation of squamous carcinoma cells and TERT-immortalized keratinocytes.IER5is epistatic toPPP2R2A, 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.

Background With the obesity epidemic reaching crisis levels, there has been attention around those who may be resilient to the effects of obesity, termed metabolically healthy obesity (MHO), who initially present without associated metabolic abnormalities. Few longitudinal studies have explored the relationship between MHO and non-alcoholic fatty liver disease (NAFLD), which we address using over 4 million primary care patient records. Methods A retrospective population-based longitudinal cohort was conducted using The Health Improvement Network (THIN) database incorporating adults with no history of NAFLD or alcohol excess at baseline. Individuals were classified according to BMI category and metabolic abnormalities (diabetes, hypertension and dyslipidaemia). Diagnosis of NAFLD during follow-up was the primary outcome measure. NAFLD was identified by Read codes. Results During a median follow-up period of 4.7 years, 12,867 (0.3%) incident cases of NAFLD were recorded in the cohort of 4,121,049 individuals. Compared to individuals with normal weight and no metabolic abnormalities, equivalent individuals who were overweight, or obese were at significantly greater risk of incident NAFLD (Adjusted HR 3.32 (95%CI 2.98–3.49), and 6.92 (6.40–7.48, respectively). Metabolic risk factors further increased risk, including in those with normal weight and 1 (2.27, 1.97–2.61) or = Conclusions MHO individuals are at greater risk of developing NAFLD compared to those with normal weight. This finding supports that the MHO phenotype is a temporary state, and weight must be considered a risk factor even before other risk factors develop. Being normal weight with metabolic abnormalities was also associated with risk of NAFLD.

The COVID-19 pandemic poses extraordinary challenges to all physicians, especially managing sick and vulnerable patients, such as those with chronic immune-mediated inflammatory diseases. Inflammatory bowel disease (IBD), rheumatoid arthritis and psoriasis share use of immunomodulators and biologic therapies that pose potential enhanced risks in a pandemic. Despite this considerable overlap, specialist societies have not issued joint guidance, understandable given the short timelines of COVID-19 response. The recently written ‘shielding’ advice for protecting sick and vulnerable patients released by the British Society of Gastroenterology (BSG),1 the British Society of Rheumatology (BSR)2 and the British Association of Dermatology (BAD)3 had some subtle differences that we want to highlight here as a catalyst for enhancing cross-speciality working. Both BSR and BAD guidelines include chronic kidney disease (CKD) in their risk stratification guidance for …

Notch signaling regulates normal squamous cell proliferation and differentiation and is frequently disrupted in squamous cell carcinomas, in which Notch is a key tumor suppressive pathway. To identify the direct targets of Notch that produce these phenotypes, we introduced a conditional Notch transgene into squamous cell carcinoma cell lines, which respond to Notch activation in 2D culture and in organoid cultures by undergoing differentiation. RNA-seq and ChIP-seq analyses show that in squamous cells Notch activates a context-specific program of gene expression that depends on lineage-specific regulatory elements, most of which lie in long- range enhancers. Among the direct Notch target genes are multiple DNA damage response genes, includingIER5, which is regulated by Notch through several enhancer elements. We show thatIER5is required for Notch-induced differentiation in squamous carcinoma cells and in TERT-immortalized keratinocytes. Its function is epistatic toPPP2R2A, which encodes the B55αsubunit of PP2A, and IER5 interacts with B55αin cells and in purified systems. These results show that Notch and DNA-damage response pathways converge in squamous cells and that some components of these pathways promote differentiation, which may serve to eliminate DNA-damaged cells from the proliferative pool in squamous epithelia. Crosstalk involving Notch and PP2A may enable Notch signaling to be tuned and integrated with other pathways that regulate squamous differentiation. Our work also suggests that squamous cell carcinomas remain responsive to Notch signaling, providing a rationale for reactivation of Notch as a therapeutic strategy in these cancers.ImpactOur findings highlight context-specific crosstalk between Notch, DNA damage response genes, and PP2A, and provide a roadmap for understanding how Notch induces the differentiation of squamous cells.

The Zinc Finger E-box binding homeobox (ZEB1/TCF8 or DeltaEF1) is at the forefront of transcription factors involved in controlling epithelial-to-mesenchymal transitions (EMT). Essentially, EMT allows for the reorganization of epithelial cells to become migratory cells with a mesenchymal phenotype. In addition to ZEB1 being involved in embryonic development, ZEB1 has also been linked to processes involving micro-RNAs, long non-coding RNAs and stem cells. In recent years there has been an accumulation of evidence with regard to ZEB1 in various cancers. Although increased ZEB1 expression has largely been associated with EMT, cancer invasion, and tumorigenicity, there have been some episodic reports that have gone against the traditional reporting of the role of ZEB1. Indicating that the function of ZEB1 and the mechanisms by which ZEB1 facilitates its activities is more complex than was once appreciated. This complexity is further exacerbated by the notion that ZEB1 can act not only as a transcriptional repressor but a transcriptional activator as well. This review seeks to shed light on the complexity of ZEB1 with respect to cancer.

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.

Background Domestic abuse ( DA ) against women is a global public health problem. Although the possible health burden could be substantial, the associations between DA and subsequent cardiometabolic disease (cardiovascular disease, hypertension, and type 2 diabetes mellitus) and all‐cause mortality are poorly understood. Methods and Results This retrospective cohort study consisted of UK ‐based primary care patients between January 1, 1995, to December 1, 2017. Overall, 18 547 women exposed to DA were matched to 72 231 unexposed women by age and lifestyle factors. The main outcomes, presented as adjusted incidence rate ratios ( IRRs ), were the risk of developing cardiovascular disease, hypertension, type 2 diabetes mellitus, and all‐cause mortality. In total, 181 exposed women experienced a cardiovascular disease event compared with 644 of the unexposed control group, relating to an increased adjusted IRR of 1.31 (95% CI , 1.11–1.55; P =0.001). There was also an increased risk of subsequent type 2 diabetes mellitus (adjusted IRR: 1.51; 95% CI , 1.30–1.76; P CI , 1.24–1.67; P DA . This observation was not seen with hypertension (adjusted IRR : 0.99; 95% CI , 0.88–1.12; P =0.873). Conclusions There is an increased risk of subsequent cardiovascular disease, type 2 diabetes mellitus, and all‐cause mortality in female survivors of DA . However, there is no association with the development of hypertension in this group, in keeping with previous literature. Considering the high prevalence of DA , clinicians should be made aware of the disproportionally increased risk and thus are encouraged to manage modifiable risk factors actively in this group.

BACKGROUND Perianal abscess [PA] is associated with inflammatory bowel disease [IBD]. The incidence of IBD after a diagnosis of PA and potential predictors of a future diagnosis of IBD are unknown. METHODS The Health Improvement Network [THIN] is a primary care database representative of the UK population. Incident cases of PA were identified between 1995 and 2017. Subjects with PA were matched to controls within the same general practice. The primary outcome was a subsequent diagnosis of Crohn's Disease [CD] or ulcerative colitis [UC]. A Cox regression model was used to assess potential predictors of a new diagnosis of CD or UC following PA. RESULTS The risk of CD was higher in the PA cohort compared with controls; adjusted hazard ratio [HR] 7.51 (95% confidence interval [CI] 4.86-11.62), p < 0.0001. The risk of UC was also higher in the PA cohort compared with controls; adjusted HR 2.03 [1.38-2.99], p < 0.0001. Anaemia in men (HR 2.82 [1.34-5.92], p = 0.002), and use of antidiarrhoeal medications (HR 2.70 [1.71-4.25], p < 0.0001) were associated with an increased risk of CD following PA. Anaemia in men (HR 2.58 [1.09-6.07], p = 0.03), diarrhoea (HR 2.18 [1.23-3.85], p = 0.007), and use of anti-diarrhoeal medication (HR 2.27 [1.19-4.30], p = 0.012) were associated with an increased risk of UC following PA. CONCLUSION Subjects with PA are at an increased risk of subsequent diagnosis of CD and UC. Clinicians should strongly consider investigation for IBD in young patients presenting with diarrhoea and anaemia [in males] following PA. Future research should discern appropriate screening strategies for this high-risk cohort.

BackgroundAchalasia 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.MethodsHospital 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.ResultsThere 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), pConclusionThe 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.

Purpose: Targeting mutations leading to PI3K/mTOR/Akt activation are of interest in thyroid cancer. We evaluated the efficacy of everolimus in aggressive, radioactive iodine–refractory (RAIR) thyroid cancer and correlated tumor mutational profiling with response. Exploratory medullary and anaplastic thyroid cancer cohorts were included. Experimental Design: This single-arm, multi-institutional phase II study was conducted from 2009 to 2013 in patients with incurable RAIR thyroid cancer who had radiographic progression six months prior to enrollment. The primary endpoint was progression-free survival (PFS) with a median follow-up of 31.8 months. The study is closed to enrollment but treatment and follow-up are ongoing. A targeted next-generation sequencing platform was used for mutational analysis. Results: Thirty-three patients with differentiated thyroid cancer (DTC), 10 with medullary thyroid cancer (MTC), and 7 with anaplastic thyroid cancer (ATC) enrolled. For the DTC cohort, median PFS was 12.9 months (95% CI, 7.3–18.5) with a 2-year PFS of 23.6% (95% CI, 10.5–39.5). Median OS was not reached; 2-year OS was 73.5% (95% CI, 53.8–85.8). Among ATC patients, 1 had a partial response and was progression-free until 17.9 months after study entry and one had disease stability for 26 months, respectively. The genomically profiled cohort enriched for PI3K/mTOR/Akt alterations. PI3K/mTOR/Akt–mutated ATC subgroups appeared to benefit from everolimus. Treatment-related adverse events were as anticipated. Conclusions: Everolimus has significant antitumor activity in thyroid cancer. While genomic profiling does not currently guide therapeutic selection in thyroid cancer patients, these data have important implications when considering the use of an mTOR inhibitor in an era of precision medicine. Clin Cancer Res; 24(7); 1546–53. ©2018 AACR.

Background and Aims: Transversus abdominis plane (TAP) block is a technique proposed to minimise pain after anterior iliac crest bone harvesting. This study aims to evaluate the postoperative pain in patients who receive ultrasound-guided TAP block to supplement routine wound infiltration. Material and Methods: A total of 143 patients aged between 6 and 22 years were randomised into two groups. Patients in group A received supplemental TAP block on the same side. Patients in group B received local anesthetic wound infiltration alone. Pain scores were compared at the first and 24th postoperative hours. Results: TAP block significantly reduced pain and delirium in the immediate postoperative period. The mean FLACC (Face, Legs, Activity, Cry, Consolability) score after 10 min was 0.8 in group A versus 1.8 in group B (P = 0.001). The mean Watcha scale at 10 min was 1.0 in group A versus 1.2 in group B (P = 0.001). After 24 h, 81.7% of patients in group A had no pain versus 59.7% in group B (P = 0.004). The incidence of intolerable pain at 24 h was 5.6% in group B versus 0% in group A (P = 0.04). Cumulative ambulation scores were significantly better in group A (P < 0.05). There was a strong and positive correlation between the analgesia and ability to ambulate comfortably at 24 h postop (Pearson's coefficient 0.95). Conclusion: Supplemental ultrasound-guided TAP block given intraoperatively reduces the postoperative pain. The incidence of emergence delirium was low. These patients were also able to ambulate earlier.

To assess the relationship between Intimate partner violence (IPV) (a highly prevalent form of domestic abuse) with the subsequent development of temporomandibular joint disorder (TMD).A retrospective open cohort study using a UK primary care database was undertaken. 18,547 women exposed to IPV were matched by age to 74,188 unexposed women. Defined through clinical codes the outcome of interest was TMD, and adjusted incidence rates (aIRR) were used to describe the relationship after considering covariates of interest.94 individuals in the exposed group were clinically coded with TMD during the study period translating to an incidence rate (IR) or 1.59 per 1000 person years. This was in comparison to 342 outcomes in the unexposed group (IR 1.21 per 1000 person years). The unadjusted IRR was 1.31 (95% CI 1.04-1.65; p 0.020) and after adjustment for important covariates increased to 1.45 (95% CI 1.14-1.84; p 0.002).Our results suggest that the development of TMD may be associated with exposure to IPV in women.In the first cohort to do so, we have identified a moderate association between Intimate partner violence exposure and subsequent development of TMD. This highlights an opportunity for screening of abuse in individuals presenting with TMD.

Primary inferior vena cava (IVC) tumors are rare with the incidence of about 0.05% overall with leiomyosarcoma (LMS) being malignant and the most common. They are late to present and slow growing, seen predominantly in females in their fifth or sixth decades and have a poor prognosis with a 5-year survival rate touching about 35% even with complete surgical resection. We present our experience with two patients diagnosed to have IVC LMS and underwent complete surgical resection of the tumor with reconstruction of IVC using coated polyester graft. In one patient, only infrarenal IVC was reconstructed, whereas in second patient, bilateral renal veins were also reconstructed along with suprarenal IVC. There is no consensus regarding the optimal treatment of this aggressive tumor, but complete excision of the tumor with wide margins with or without IVC reconstruction have been widely accepted as primary modality of treatment. Neoadjuvant or adjuvant chemoradiotherapy have limited role in the management of this rare tumor.

Cancer metabolism has emerged as one of the most interesting old ideas being revisited from a new perspective. In the early 20th century Otto Warburg declared metabolism the prime cause in a disease of many secondary causes, and this statement seems more prescient in view of modern expositions into the true nature of tumor evolution. As the complexity of tumor heterogeneity becomes more clear from a genetic perspective, it is important to consider the inevitably heterogeneous metabolic components of the tumor and the tumor microenvironment. High grade gliomas remain one of the most difficult to treat solid tumors, due in part to the highly vascularized nature of the tumor and the maintenance of more resistant stem-like subpopulations within the tumor. Maintenance of glioma stem cells (GSCs) requires specific alterations within the cells and the greater tumor microenvironment with regards to signaling and metabolism. Specific niches within gliomas help foster the survival of stem-like sub-populations of cells with high tumorigenicity and high metabolic plasticity. Understanding these maintenance pathways and the metabolic dependencies within the niche may highlight potential avenues of addressing tumor resistance and recurrence in glioma patients.

A 33-year-old man with ulcerative colitis presented with 5-day history of fever, night sweats, abdominal pain and increased stool frequency. He was on mesalazine M/R 1 g once daily, 6-mercaptopurine (6-MP) 75 mg once daily and prednisolone 40 mg once daily. Examination revealed fever and tachycardia. Blood examinations identified a persistent leucopenia, C reactive protein of 23 mg/L and an initial alanine transaminase of 855 IU/L. Flexible sigmoidoscopy revealed well-demarcated, punched-out ulcers in the proximal rectum and distal sigmoid, with histology pathognomonic of cytomegalovirus (CMV). CMV DNA PCR was 51 140 copies/mL. Despite prompt withdrawal of 6-MP, steroids and initiation of intravenous ganciclovir on day 2 of admission, his systemic illness, diarrhoea and fever persisted until day 19 of antiviral therapy. Other copathogens and lymphoma were ruled out on serology and CT scan, respectively. After an unusually prolonged course of antiviral therapy, the patient made a full clinical recovery, bloods normalised and there were two consecutive undetectable CMV DNA PCRs.

Objectives Pediatric eustachian tube dysfunction (ETD), otitis media with effusion (OME), and tympanic membrane retraction (TMR) have been well studied, but no large analyses have described the associated burden beyond childhood. The potential impact and feasibility of prospective trials designed to optimize management of affected adults are thus unclear. Our objectives were therefore (1) to determine the national visit burden associated with ETD/OME/TMR beyond childhood and (2) to examine risk factors specific to adults, highlighting differences in comparison with children. Study Design Cross-sectional analysis of a national database. Setting Ambulatory visits in the United States. Methods Epidemiologic analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (2005-2012) included data from 761,291 observations representing 9,369,388,092 visits. Chi-square test with Bonferroni adjustment for multiple comparisons was utilized for hypothesis testing. Results Visits related to ETD/OME/TMR exceeded 2 million per annum in patients 0 to 20 years of age (mean 2,625,965; range 2,239,288-3,329,858). Among those20 years old, visits also exceeded 2 million (mean, 2,025,050; range, 1,550,669-2,353,799). Characteristics differed according to age: whereas ETD/OME/TMR affected more males20 years, females were more frequently diagnosed in the older age group ( P.0001). Patients20 to 40 years of age were the most likely to visit the emergency department ( P = .0022). There were no statistically significant differences per season or region. The related diagnoses of cholesteatoma and chronic otitis media prompted additional visits. Conclusions ETD/OME/TMR is associated with a visit burden for adults that extends beyond childhood. Among adults, there may also be age-related differences in patient characteristics.

Background: Fresh frozen plasma (FFP) should be thawed before transfusing to the patient. Prolonged or uncontrolled thawing can denature plasma proteins. The potential risk of contamination by wet thawing had always been a point of concern. Aims: Here, we compared and evaluated the effect of thawing on clotting factor activities by two different methods (wet and dry) and other factors such as risk of bacterial contamination, throughput, turnaround time, and efficacy of thawing. Subjects and Methods: All FFPs were prepared from Group O donors and stored at −40°C. Twenty-one FFPs were thawed in Plasmatherm II at 45°C for 15 min and another 21 were thawed in thawing bath at 37°C for 20–30 min randomly. Analysis of prothrombin time, activated partial thromboplastin time, fibrinogen, and factor VIII was done in ACL TOP 300 (IL) at the time of preparation and immediately after thawing of FFPs. Volume, duration of thawing, ease of use, accessibility, and equipment maintenance were also compared. Results: There was a statistically significant difference in coagulation parameters after thawing in both methods compared to the time of preparation (P < 0.05), but all values were within normal limits. There was no significant difference in coagulation parameters between the two methods (P > 0.05). Mixed bacterial growth was observed from swabs taken from the water bath. Conclusion: Plasmatherm II can be a good alternative to water bath to rapidly thaw FFPs by preserving coagulation factors and eliminating the risk of bacterial contamination.

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.

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

BackgroundInternationally, intimate partner violence (IPV) cohorts have demonstrated associations with depression and anxiety. However, this association has not yet been described in a UK population, nor has the association with serious mental illness (SMI).AimsTo explore the relationship between IPV exposure and mental illness in a UK population.MethodWe designed a retrospective cohort study whereby we matched 18 547 women exposed to IPV to 74 188 unexposed women. Outcomes of interest (anxiety, depression and SMI) were identified through clinical codes.ResultsAt baseline, 9174 (49.5%) women in the exposed group had some form of mental illness compared with 17 768 (24.0%) in the unexposed group, described as an adjusted odds ratio of 2.62 (95% CI 2.52–2.72). Excluding those with mental illness at baseline, 1254 exposed women (incidence rate 46.62 per 1000 person-years) went on to present with any type of mental illness compared with 3119 unexposed women (incidence rate 14.93 per 1000 person-years), with an aIRR of 2.77 (95% CI 2.58–2.97). Anxiety (aIRR 1.99, 95% CI 1.80–2.20), depression (aIRR 3.05, 95% CI 2.81–3.31) and SMI (aIRR 3.08, 95% CI 2.19–4.32) were all associated with exposure to IPV.ConclusionsIPV remains a significant public health issue in the UK. We have demonstrated the significant recorded mental health burden associated with IPV in primary care, at both baseline and following exposure. Clinicians must be aware of this association to reduce mental illness diagnostic delay and improve management of psychological outcomes in this group of patients.

Background The effect of smoking on inflammatory bowel diseases (IBD) may be heterogeneous across ethnicity and geography. This is a systematic review of smoking prevalence across global IBD cohorts. 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 the 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. 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). Conclusions 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.

Introduction Primary sclerosing cholangitis[PSC] is the classical hepatobiliary manifestation of inflammatory bowel disease[IBD] for which liver transplantation[LT] is the only curative therapy.In this study,we provide pooled incidence rates[IR] and time trends of (1)colorectal cancer[CRC], (2)flares in IBD activity and (3)colectomy rates post LT, through systematic review and meta-analysis. Methods A systematic literature search of Medline and Embase was undertaken to identify pertinent studies from 1981 to 2014.Included studies were assigned to one or more of the three analytical streams.The ‘meta’ package (R Studio (V.1.1.463)) and Revman was used to pool IRs and HRs from individual studies using a random effects model respectively. Results 42 studies qualified for inclusion in the systematic review.20 studies detailing the clinical course of 1994 patients(cumulative 9874 patient years(PY)) were pooled to assess the occurrence of dysplasia or CRC(combined endpoint) and CRC only; yielding an IR of 14.97 (95%CI9.74–23.02) and 9.21(95%CI6.01–14.09) per 1000 PY,respectively. Heterogeneity was considerable(I2=86%).The incidence of post LT CRC was seen to be decreasing over the past decade(figure 1A).The estimated colectomy rate following OLT was IR 23.18(95%CI16.74–32.08, I2=84%) per 1000 PY. IR for colectomy due to dysplasia/CRC was 11.25 per 1000 PY(95%CI6.43–19.68) and decreasing over time(figure 1B).By contrast, deterioration in IBD activity necessitating colectomy was noted for IR 13.26 per 1000 PY(95% CI 9.95–17.66), with no change in the incidence rate over study duration(figure 1C).9 studies reported on post LT clinical course of IBD according to endoscopy findings or need for escalation in IBD therapy.27.6% of patients (n=584) experienced deterioration in IBD activity after LT.The effect of ursodeoxycholic acid [UDCA] on the risk of CRC after LT was examined by 3 studies.Due to data availability,only 2 studies could be pooled.Use of UDCA increased the risk of CRC post LT in the PSC cohort; HR 2.90 (95%CI 1.37–6.11).Studies examining the impact of UDCA on colectomy and IBD activity post-LT were inconclusive. Conclusion The heightened risk of CRC mandates ongoing colonoscopic surveillance in the PSC/IBD LT population,although the incidence appears to be decreasing.Identification of risk predictors impacting the course of IBD is of critical importance,given that deterioration in activity appears to be the principal indication for colectomy post LT.

Aims Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the leading causes of liver transplantation in the West. This study seeks to examine whether women with gestational diabetes mellitus (GDM) are at increased risk of developing NAFLD compared to women without GDM. Methods We conducted a population-based retrospective matched-controlled cohort study utilising The Health Improvement Network (THIN), a large primary care database representative of the United Kingdom population, between 01/01/1990 to 31/05/2016 followed by systematic review of available literature. The study population included 9640 women with GDM and 31,296 controls without GDM, matched for age, body mass index (BMI) and time of pregnancy. All study participants were free from NAFLD diagnosis at study entry. Patients with GDM and patients developing NAFLD were identified by clinical codes. Results The median (range) follow-up duration was similar in women with and without GDM (2.95 (1.21–6.01) vs 2.85 (1.14–5.75) years respectively). Unadjusted incidence rate ratio (IRR) for NAFLD development in women with vs without GDM was 3.28 (95% CI 2.14–5.02), which remained significant after adjustment for wide range of potential confounders (IRR 2.70; 95% CI 1.744–4.19). The risk of NAFLD in GDM remained high (IRR 2.46: 95% CI 1.51–4.00) despite women being censored after they developed type 2 diabetes. The meta-analysis of 3 studies (including the current study) showed increased NAFLD risk in women with vs without GDM (OR 2.60; 95% CI 1.90–3.57, I2 = 0%). As our study is based on routine clinical diagnosis of NAFLD, this study could potentially have underestimated the risk of NAFLD development. Conclusions Women with GDM are at increased risk of developing NAFLD in their later life compared to women without GDM regardless of the development of type 2 diabetes. Clinicians should have a low threshold to investigate women with history of GDM for the presence of NAFLD. Further studies to identify screening strategies are needed.

Osteomyelitis is an inflammatory condition of the bone. Pathological fractures associated with osteomyelitis are difficult to manage and are time-consuming, as fractures have to be treated along with the underlying disease. This article describes a case report on the pathological fracture of the mandible secondary to chronic osteomyelitis.

Fibrous histiocytoma can present as malignant or benign and may involve either the soft or hard tissues. The treatment of choice to oral BFH is generally en-block resection. The prognosis is good and the oral BFH recurs only if not completely excised. Hereby presenting a case of a 29 year old male with a chief complaint of pain and swelling in the left side of the face since 2 months. Treatment plan of Subtotal maxillectomy was performed under general anesthesia through a Weber Ferguson incision with infraorbital extension after histopathological and radiological confirmation.

The word “ankylosis” is derived from a Greek word meaning “Stiff.” Temporomandibular joint (TMJ) ankylosis is the bony or fibrous union of the joint and its components. The characteristic feature is the limitation in mouth opening. It affects the speck, mastication, facial growth, and appearance. The article describes a case report on severe bony ankylosis TMJ ankylosis secondary to trauma.

Purpose: The clinical impact of next-generation sequencing (NGS) in patients with head and neck squamous cell carcinoma (HNSCC) has not been described. We aimed to evaluate the clinical impact of NGS in the routine care of patients with HNSCC and to correlate genomic alterations with clinical outcomes. Experimental Design: Single-center study examining targeted NGS platform used to sequence tumor DNA obtained from 213 HNSCC patients evaluated in outpatient head and neck oncology clinic between August 2011 and December 2014. We correlated tumor genomic profiling results with clinical outcomes. Results: PI3K/RTK pathway activation occurred frequently [activating PIK3CA mutation or amplification (13%), PTEN inactivation (3%), RAS activation (6%), EGFR or ERBB2 activation (9%)]. Alterations in pathways affecting cell-cycle regulation [CCND1 amplification (9%), CDKN2A inactivation (17%), BRCA2 inactivation (2%)] and squamous differentiation [NOTCH1 inactivation (8%) andEP300 inactivation (6%)] were identified. PIK3CA amplification (n = 43), not PIK3CA mutation, was associated with significantly poorer progression-free survival (P = 0.0006). Oncogenic RAS mutations (n = 13) were associated with significantly poorer progression-free survival (P = 0.0001) and lower overall survival (P = 0.003). Eight patients with advanced, treatment-refractory HNSCC enrolled on clinical trials matched to tumor profiling results, and 50% achieved a partial response. Conclusions: Incorporation of NGS clinical assays into the routine care of patients with HNSCC is feasible and may readily facilitate enrollment into clinical trials of targeted therapy with a higher likelihood of success. Data can be utilized for discovery of genomic biomarkers of outcome. PIK3CA amplification and RAS mutations were frequently identified and associated with poorer prognosis in this cohort. Clin Cancer Res; 22(12); 2939–49. ©2016 AACR.

Background: Medical education is inherently stressful and can be a source of anxiety and depression if a student fails to cope with the vast syllabus. The personality of the learner, if apt, will help him perform better as a student and doctor. It would also act as a stabilizing influence on the moods of the learners while facing academic challenges. This study was done to analyse the effects of personality on the moods, namely stress, anxiety and depression levels. Methods: The study was done using validated tools, the big 5 personality and the depression, anxiety and stress scale questionnaire (DASS). The study sample consisted of 200 first and second year medical students in an Indian medical college. ANOVA and Pearson’s correlation tests were used. Results: The results show that personality traits have a highly positive influence on development of stress, anxiety and depression and no influence of gender noted. Conclusions: In addition to academic scores, personality testing may be advised before the student gains entry into the medical profession.

Background: Medical education is at cross roads today with a mismatch between students’ expectations of their performance and the reality. This led us to explore the reason for the academic decline. During our search, we found that metacognitive awareness plays a key role in moulding the learning skills of adult learners. Hence this study was conducted to evaluate the metacognitive awareness of medical students studying in the first year of MBBS. Methods: 100 first year medical students were included in the study and metacognitive awareness inventory questionnaire, a validated tool was administered to the students. This measures metacognitive knowledge and regulation. The results were obtained, tabulated and analysed. Results: Metacognitive awareness among medical students was average. Metacognitive knowledge was found to be significantly better than regulation. On comparing the genders, we note that females have better metacognitive regulation while males score higher in metacognitive knowledge which was statistically significant. Conclusions: The findings of the present study points towards the need of introduction of metacognitive strategies in the medical curriculum with more emphasis on problem based learning in order to make our learners become independent thinkers and efficient care givers.

Background: Diabetic foot ulcers are very common complication in diabetic patients and important cause of morbidity to patient and affect quality of life. Ischemia forms a major risk factor for non-healing ulcer. Even after revascularization these ulcers shows delay in healing. Based on studies by Ian Taylor who proposed angiosome concept, it is said that non achievement of direct flow to ulcer area may be a reason for this. Objective of this study was to evaluate the outcome in angiosome based revascularization in diabetic foot ulcer. Methods: A prospective observational study was done which included 50 diabetic foot ulcer patient who underwent endovascular revascularization in department of general surgery in our hospital during the period October 2013 to March 2015 and they were followed up for 6 months to look for ulcer healing rate , ulcer recurrence , leg salvage rate and major amputation. Results: Out of 50 participants in 52% direct revascularization was done. Base line characteristics of both the groups were comparable except gender (where proportion of females was higher in indirect group), CKD, smoking, UTCWS grade of ulcer which were more in direct group. Ulcer predominantly affected toes (70%) and Anterior Tibial angiosome was the most common (50%) angiosome involved by clinical classification. Most common affected arterial segment pattern by Peripheral angiogram was multi segmental followed by infra popliteal disease. In 78.3% of cases ulcer healed at 6 months in the indirect group whereas 57.7% patients had healed ulcers at 6 months in the direct group (P value = 0.12). Female gender, CKD, smoking and ulcer grade found to have no association with healing at 6 months. No significant difference was found in leg salvage rate, ulcer recurrence and major amputation. Conclusions: Endovascular revascularization is a good modality to reduce morbidity in diabetic foot ulcer patients. There was no significant difference in outcome between these two groups.