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Background and study aim The clinical impact of eosinophilic esophagitis (EoE) limited to the distal esophagus (Lim-EE) vs. diffuse involvement (Dif-EE) is unknown. This study compared clinical characteristics and outcomes of Lim-EE vs. Dif-EE. Patients and methods This retrospective, single-center study of patients with EoE between December 2011 and December 2019 evaluated treatment response based on repeated pathology and/or clinical improvement using comparative statistics. Results 479 patients were identified (126 Lim-EE, 353 Dif-EE). Lim-EE patients had a higher incidence of endoscopically identified esophagitis (23.0 % vs. 14.7 %; P = 0.04), were older (50.8 [SD 16.2] vs. 46.4 [SD 15.3] years; P = 0.007), and were more likely to present with iron deficiency anemia (5.6 % vs. 1.7 %; P = 0.05), dyspepsia (15.1 % vs. 8.8 %; P = 0.06) or for Barrett’s surveillance (10.3 % vs. 3.7 %; P = 0.02). Patients with Dif-EE presented more frequently with dysphagia (57.2 % vs. 45.2 %; P = 0.02). Both groups had similar proton pump inhibitor (87.2 % vs. 83.3 %; P = 0.37) and steroid (12.8 % vs. 21.4 %; P = 0.14) use. Patients with Lim-EE had a better clinicopathologic response (61.5 % vs. 44.8 %; P = 0.009). On multivariate analysis, EoE extent predicted treatment response with an odds ratio of 1.89 (95 % confidence interval 1.13–3.20; P = 0.02). However, treatment response based only on repeat biopsy results showed no statistical difference between Lim-EE (52.5 %) and Dif-EE (39.7 %; P = 0.15). Conclusions Lim-EE may represent a distinct phenotype separate from Dif-EE, with more overlap with gastroesophageal reflux disease and better treatment response.

Lymphocytic esophagitis is a rare esophageal condition. Our knowledge of potential risk factors and treatment outcomes of lymphocytic esophagitis is limited. To investigate potential risk factors associated with the development of lymphocytic esophagitis and compare clinical characteristics and treatment outcomes of patients diagnosed with lymphocytic esophagitis to patients diagnosed with eosinophilic esophagitis. This is a multicenter retrospective study. Lymphocytic esophagitis patients were identified based on pathology results between 1997 and 2019. Control groups consisted of patients with normal esophageal biopsies and patients diagnosed with eosinophilic esophagitis. Thirteen potential risk factors for lymphocytic esophagitis were analyzed using univariate and multivariate models including IBD, achalasia, hyperlipidemia, hypothyroidism, celiac sprue, CVID, H. pylori, thymoma, aspirin, opioids, ACE-I, metformin, and statin use. Comparative statistics were performed. Ninety-four adult patients with lymphocytic esophagitis, 344 with eosinophilic esophagitis, and 5202 control patients with normal esophageal biopsies were analyzed. Age older than 60 [adjusted odd ratio (AOR) 1.03, 95% CI 1.02–1.05, p = 0.001], aspirin use (2.7, 95% CI 1.4–4.9, p = 0.001), statin use (2.2, 95% CI 1.2–4.2, p = 0.01), or a diagnosis of achalasia (2.4, 95% 1.08–5.67, p = 0.03) were associated with lymphocytic esophagitis. Compared to eosinophilic esophagitis, lymphocytic esophagitis patients were more likely to respond to medical treatment (95% CI 2.54–12.8, p = 0.0001). Our data suggests that lymphocytic esophagitis is more likely to be found in older female patients and is significantly associated with achalasia, statin, and aspirin use. Compared to eosinophilic esophagitis, lymphocytic esophagitis is more likely to respond to treatment with medical therapy.

Several case reports show accumulation of eosinophils in pancreatitis patients and term the disease as “eosinophilic pancreatitis (EP)”. EP usually presents with a pancreatic tumour and abdominal pain in obstructive jaundice, which is generally not diagnosed until the patient undergoes pancreatic resection. Histologically, EP reveals distinct patterns like diffused, periductal, acinar, and septal inflammatory infiltrates with eosinophils, eosinophilic phlebitis, and localised extreme eosinophilic infiltrates related with pseudocyst formation. EP patients also have elevated serum IgE levels with high eosinophil counts in the pancreas as well as in other organs such as the gastrointestinal tract, which is termed as eosinophilic gastroenteritis. Due to the lack of knowledge based on just a few case reports, it is considered that eosinophilic infiltration is quite rare in the pancreas; therefore, the significance of eosinophils in pancreatitis is not yet established. This review assesses the current understanding of eosinophilic pancreatitis and the important role of eosinophils in promoting pancreatic fibrosis including malignancy.

Diffuse idiopathic skeletal hyperostosis (DISH), being an asymptomatic condition, is generally discovered incidentally on imaging and it has not received much attention for research on clinical grounds. We assessed the prevalence of DISH, its associated factors, and interobserver agreement for computed tomography (CT)-based diagnosis of DISH. CT scans of chest, abdomen, and pelvis performed for various clinical indications were retrospectively reviewed. Resnick criteria were used for the diagnosis of DISH. Moreover, enthesopathy along with comorbidities was assessed. CT scans were observed by 3 observers having different experience levels. Out of total 416 patients, the prevalence of DISH was 30.8%. Strong positive agreement was observed between observer 1 and 2 (k = 0.89), observer 1 and 3 (k = 0.91), and observer 2 and 3 (k = 0.94). Reporting rate of DISH was 59.3%. Regression analyses showed that enthesopathy was 2.45 times (adjusted odds ratio [AOR]: 2.45, 95% confidence intervals [CI]: 1.48–4.05), diabetic patients were 4.74 times (AOR: 4.74, 95% CI: 2.89–7.78) while hypertensive patients were 2.17 times (AOR: 2.17, 95% CI: 1.30–3.62) more likely to have DISH in comparison to those who do not have DISH. A high prevalence of DISH was observed in our cohort. Enthesopathy and comorbidities like diabetes and hypertension were significant factors associated with DISH. Moreover, excellent agreement was observed in defining DISH on CT according to Resnick criteria.

BACKGROUND Depression is frequent among youth living with HIV (YLWH). Studies suggest that manualized treatment guided by symptom measurement is more efficacious than usual care. SETTING This study evaluated manualized, measurement-guided depression treatment among YLWH, aged 12-24 years at 13 US sites of the International Maternal Pediatric Adolescent AIDS Clinical Trials Network. METHODS Using restricted randomization, sites were assigned to either a 24-week, combination cognitive behavioral therapy and medication management algorithm (COMB-R) tailored for YLWH or to enhanced standard of care, which provided standard psychotherapy and medication management. Eligibility included diagnosis of nonpsychotic depression and current depressive symptoms. Arm comparisons used t tests on site-level means. RESULTS Thirteen sites enrolled 156 YLWH, with a median of 13 participants per site (range 2-16). At baseline, there were no significant differences between arms on demographic factors, severity of depression, or HIV status. The average site-level participant characteristics were as follows: mean age of 21 years, 45% male, 61% Black, and 53% acquired HIV through perinatal transmission. At week 24, youth at COMB-R sites, compared with enhanced standard of care sites, reported significantly fewer depressive symptoms on the Quick Inventory for Depression Symptomatology Self-Report (QIDS-SR score 6.7 vs. 10.6, P = 0.01) and a greater proportion in remission (QIDS-SR score ≤ 5; 47.9% vs. 17.0%, P = 0.01). The site mean HIV viral load and CD4 T-cell level were not significantly different between arms at week 24. CONCLUSIONS A manualized, measurement-guided psychotherapy and medication management algorithm tailored for YLWH significantly reduced depressive symptoms compared with standard care at HIV clinics.

Patients with chronic pancreatitis have an increased risk of pancreatic malignancy, but the mechanisms underlying this relationship are poorly understood. We developed a mouse model of chronic pancreatitis by treatment with a combination of cerulein and azoxymethane. In our model, we show that cerulein and azoxymethane treated mice develop pathological malignant phenotype and associated lung inflammation. We observed chronic pancreatitis-associated induction of proinflammatory cytokines such as interleukin-6, interleukin-15, and granulocyte-macrophage colony-stimulating factor, along with accumulation of macrophages and eosinophilic inflammation. We also observed eosinophils degranulation, pancreatic stellate cell activation-mediated epithelial-to-mesenchymal transition-associated proteins that display a pancreatic malignant phenotype including acinar-to-ductal metaplasia and acinar cell atrophy. We observed highly induced interleukin-15 that has been earlier reported to have a protective role against fibrosis and malignancy; therefore, further evaluated its role in our mouse model of chronic pancreatitis. We observed that introduction of recombinant interleukin-15 has indeed improve chronic pancreatitis-associated epithelial-to-mesenchymal transition-mediated development of a malignant phenotype in the mouse model of chronic pancreatitis. In conclusion, we present evidence that rIL-15 overexpression improves eosinophilic inflammation-induced epithelial-to-mesenchymal transition-mediated progression of pancreatic remodeling associated malignant phenotype and acute lung injury by inducing NKT cells and IFN-γ mediated innate immunity in experimental pancreatitis.

Endogenous IL-15 deficiency promotes lung fibrosis; therefore, we examined the effect of induced IL-15 in restricting the progression of lung fibrosis. Our objective in this work was to establish a novel therapeutic molecule for pulmonary fibrosis. Western blot, qPCR, and ELISA were performed on the lung tissues of IL-15–deficient mice, and recombinant IL-15 (rIL-15)–treated CC10–IL-13 and CC10–TGF-α mice, and allergen-challenged CC10–IL-15 mice were examined to establish the antifibrotic effect of IL-15 in lung fibrosis. We show that endogenous IL-15 deficiency induces baseline profibrotic cytokine and collagen accumulation in the lung, and pharmacological delivery of rIL-15 downregulates Aspergillus antigen–induced lung collagen, the profibrotic cytokines IL-13 and TGF-β1, and α-SMA(+) and FSP1(+) cells in mice. To confirm that overexpression of IL-15 diminishes pulmonary fibrosis, we generated CC10-rtTA-tetO7–IL-15 transgenic mice and challenged them with Aspergillus antigen. Aspergillus antigen–challenged, doxycycline (DOX)-treated CC10–IL-15 transgenic mice exhibited decreased collagen accumulation, profibrotic cytokine (IL-13 and TGF-β1) expression, and α-SMA(+) and FSP1(+) cells compared with IL-15–overexpressing mice not treated with DOX. Additionally, to establish that the antifibrotic effect of IL-15 is not limited to allergen-induced fibrosis, we showed that rIL-15 or IL-15 agonist treatment restricted pulmonary fibrosis even in CC10–IL-13 and CC10–TGF-α mice. Mechanistically, we show that T-helper cell type 17 suppressor IL-15–responsive RORγ(+) T regulatory cells are induced in DOX-treated, allergen-challenged IL-15–overexpressing mice, which may be a novel pathway for restricting progression of pulmonary fibrosis. Taken together, our data establishes antifibrotic activity of IL-15 that might be a novel therapeutic molecule to combat the development of pulmonary fibrosis.

ObjectiveChronic pancreatitis (CP) is an inflammatory disease with progressive fibrosis leading to exocrine and endocrine dysfunction. Currently, there are no approved effective therapies for CP. Stimulator of interferon genes (STING) signalling is a key innate immune sensor of DNA. In this study, we evaluated the role of STING signalling in CP.DesignWe used an experimental model of CP to test the effect of STING signalling in STING wild-type and knockout mice as well as bone marrow chimaeras (BMCs). STING was activated using a pharmacological agent. Since we found changes in Th17 cells, we used neutralising and control antibodies to determine the role of IL-17A. The effect of STING signalling was further explored in IL-17A generation and we examined the effect of IL-17A on pancreatic stellate cells (PSCs). Human pancreas from patients with CP and without CP were also stained for IL-17A.ResultsSTING activation decreased CP-associated pancreatic inflammation and fibrosis, whereas absence of STING led to worsening of the disease. BMCs showed that leucocytes play an important role in STING signalling–mediated amelioration of experimental CP. STING deletion was associated with increased Th17 cell infiltration in the pancreas, whereas STING agonist limited this Th17 response. Importantly, anti-IL-17A antibody treatment mitigated the severity of CP in the absence of STING signalling. STING deficiency promoted Th17 polarisation and PSCs express functional IL-17 receptor by upregulating fibrosis genes. Compared with tumour margins, pancreas from patients with CP had significant increase in IL-17A+ cells.ConclusionUnlike acute pancreatitis, STING activation is protective in CP. STING signalling is important in regulating adaptive immune responses by diminishing generation of IL-17A during CP and presents a novel therapeutic target for CP.

Pancreatitis is an inflammatory disease characterized by the induction of several proinflammatory cytokines like interleukin (IL)-6, IL-8, IL-1β, and IL-1. Recently, the multifunctional innate cytokine IL-15 has been implicated in the protection of several diseases, including cancer. Tissue fibrosis is one of the major problems in successfully treating chronic pancreatitis pathogenesis. Therefore, we tested the hypothesis that recombinant IL-15 (rIL-15) treatment may induce innate tissue responses and its overexpression will improve the pathogenesis of cerulein-induced chronic pancreatitis, associated remodeling, and fibrosis. We observed atrophy of acinar cells, increased inflammation, and increased deposition of perivascular collagen, the upregulated protein level of transforming growth factor (TGF)-β1, α-smooth muscle actin (α-SMA), and collagen-1 in cerulein-induced chronic pancreatitis in mice. Furthermore, we reported that rIL-15 treatment protects mice from the cerulein-induced chronic pancreatitis pathogenesis, including acinar cell atrophy, and perivascular accumulation of tissue collagen followed by downregulation of profibrotic genes such as TGF-β1, α-SMA, collagen-1, collagen-3, and fibronectin in cerulein-induced chronic pancreatitis in mice. Mechanistically, we show that IL-15-mediated increase of interferon-γ-responsive invariant natural killer T (iNKT) cells in the blood and tissue protects cerulein-induced pancreatic pathogenesis in mice. Of note, a reduction in iNKT cells was also observed in human chronic pancreatitis compared with normal individuals. Taken together, these data suggest that IL-15 treatment may be a novel therapeutic strategy for treating chronic pancreatitis pathogenesis. NEW & NOTEWORTHY Pancreatic fibrosis is a major concern for the successful treatment of chronic pancreatitis and pancreatic cancer. Therefore, restriction in the progression of fibrosis is the promising approach to manage the pancreatitis pathogenesis. Herein, we present in vivo evidences that pharmacological treatment of recombinant interleukin-15 improves remodeling and fibrosis in cerulein-induced chronic pancreatitis in mice. Our observations indicate that interleukin-15 immunotherapy may be a possible and potential strategy for restricting the progression of fibrosis in chronic pancreatitis.

Eosinophils are an important subtype of leukocytes derived from bone marrow multipotent hematopoietic stem cells and represent about 1% of leukocytes in circulating blood. In homeostatic conditions, eosinophils reside in the intestine to maintain the balance of immune responses by communicating with gut microbes without causing inflammation. However, under the stressed or diseased condition, eosinophils degranulate, releasing their granule-derived cytotoxic proteins that are involved in inflammatory responses. Various eosinophil-associated inflammatory diseases are eosinophilic esophagitis (EoE), eosinophilic gastroenteritis (EG), and eosinophilic colitis (EC), together called EGID, asthma, hypereosinophilic syndrome, and eosinophilic pneumonia (EP). Eosinophil degranulation results in the release of their four toxic proteins [major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN)] which promote disease pathogenesis. Pancreatitis is the inflammatory disease of the pancreas that arises due to blockage of the pancreatic duct, trypsinogen mutation, alcohol consumption, and repeated occurrence of pancreatitis leading to chronic pancreatitis (CP); subsequently some CP patients may also develop pancreatic cancer. The presence of eosinophils is now shown in various case reports with acute, recurrent acute, and chronic pancreatitis and pancreatic cancer indicating the role of eosinophils in the pathogenesis of various pancreatic inflammatory disorders. However, the details of eosinophil accumulation during pancreatic diseases are not well explored and need further attention. Overall, the chapter provides the current understanding of reported eosinophils associated with inflammatory diseases like EGID diseases, asthma, and pancreatic disorders, i.e., acute, chronic pancreatitis, and pancreatic cancer. This knowledge will be helpful for future studies to develop novel treatment options for the eosinophils associated diseases. Therefore, more efforts are needed to perform preclinical and clinical studies in this field for the successful development of eosinophil-targeting treatments for a variety of eosinophil-associated diseases.

The current study presents first CP murine model that show IL-18–induced eosinophil inflammation-mediated induction of oncogenic proteins and several pathological malignant characteristics., Reports indicate that accumulated macrophages in the pancreas are responsible for promoting the pathogenesis of chronic pancreatitis (CP). Recently, macrophage-secreted cytokines have been implicated in promoting pancreatic acinar-to-ductal metaplasia (ADM). This study aims to establish the role of accumulated macrophage-activated NLRP3-IL-18-eosinophil mechanistic pathway in promoting several characteristics of pancreatic malignancy in CP. We report that in a murine model of pancreatic cancer (PC), accumulated macrophages are the source of NLRP3-regulated IL-18, which promotes eosinophilic inflammation-mediated accumulation to periductal mucin and collagen, including the formation of ADM, pancreatic intraepithelial neoplasia (PanINs), and intraductal papillary mucinous neoplasm. Most importantly, we show improved malignant characteristics with reduced levels of oncogenes in an anti–IL-18 neutralized and IL-18 gene deficient murine model of CP. Last, human biopsies validated that NLRP3-IL-18–induced eosinophils accumulate near the ducts, showing PanINs formation in PC. Taken together, we present the evidence on the role of IL-18–induced eosinophilia in the development of PC phenotype like ADM, PanINs, and ductal cell differentiation in inflammation-induced CP.

Eosinophils comprise approximately 1-4% of total blood leukocytes that reside in the intestine, bone marrow, mammary gland, and adipose tissues to maintain innate immunity in healthy individuals. Eosinophils have four toxic granules known as major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN), and upon degranulation, these granules promote pathogenesis of inflammatory diseases like allergy, asthma, dermatitis, and gastrointestinal disorders. Additionally, the role of eosinophils is underscored in exocrine disorders including pancreatitis. Chronic pancreatitis (CP) is an inflammatory disorder that occurs due to the alcohol consumption, blockage of the pancreatic duct, and trypsinogen mutation. Eosinophil levels are detected in higher numbers in both CP and pancreatic cancer patients compared with healthy individuals. The mechanistic understanding of chronic inflammation-induced pancreatic malignancy has not yet been reached and requires further exploration. This review provides a comprehensive summary of the epidemiology, pathophysiology, evaluation, and management of eosinophil-associated pancreatic disorders and further summarizes current evidence regarding risk factors, pathophysiology, clinical features, diagnostic evaluation, treatment, and prognosis of eosinophilic pancreatitis (EP) and pancreatic cancer.

Mucoceles are benign, encapsulated, expansible, locally invasive masses within a paranasal sinus filled with mucus and lined by epithelium. Sphenoid sinus mucoceles are relatively rare, accounting for only 1% of all paranasal sinus mucoceles. Usually presenting with headache but can rarely result in visual defect, diplopia and at times, ptosis. We present two cases of sphenoid sinus mucocele where patient presented with ophthalmoplegia, ptosis and/or sudden onset vision loss. With the help of imaging studies like CT scan and MRI of paranasal sinus diagnosis was made and immediate surgical intervention was planned which resulted in acceptable improvement of symptoms and vision.

Postural instability is a disease milestone signaling advanced disease. To estimate the onset of postural instability in monogenic parkinsonisms. We systematically reviewed studies (PubMed 1996–2017) in SNCA, PRKN, PINK1, DJ-1, LRRK2, ATP13A2, FBXO7, VPS35, DNAJC6, or SYNJ1-related monogenic parkinsonisms, with documented postural instability. Genes with ≥ 15 patients were included in an individual-patient meta-analysis and compared with a retrospectively collected sporadic Parkinson’s disease cohort from our center. The primary outcome measure was the progression-free survival from postural instability using Kaplan–Meier survival curves. Cox proportional hazards analyses were summarized using hazards ratio (HR). Of 2085 eligible studies, 124 met full criteria (636 patients) for the systematic review, whereas a total of 871 subjects (270 from sporadic cohort, 601 monogenic parkinsonisms) were included in the individual-patient meta-analysis. Postural instability was reported in 80% of DJ-1, 40% of PRKN, 39% of PINK1, 34% of ATP13A2, 31% of LRRK2, and 29% of SNCA patients. Progression-free survival from postural instability at 10 years after disease onset was longest in ATP13A2 (97%) and shortest in SNCA (50%). Halfway between these two extremes were PRKN (88%), PINK1 (87%), and LRRK2 (81%), similar to sporadic Parkinson’s disease (72%). Higher risk of postural instability was observed in SNCA (HR = 3.2, p = 0.007) and DJ-1 (HR = 3.96, p = 0.001) compared to sporadic Parkinson’s disease. Young age at onset in PINK1 and female sex in LRRK2 were associated with a decreased risk of postural instability. Monogenic parkinsonisms exhibit differential timelines to postural instability, informing prognostic counseling and interpretation of future genotype-specific treatment trials.

BACKGROUND:Perinatally HIV-exposed but uninfected (HEU) children have elevated risk of late language emergence at 1 year of age, with possible links to in utero antiretroviral (ARV) exposure. We investigated possible risks for speech impairments (SIs) and language impairments (LI) in preschool monolingual HEU children in the United States. METHODS:Speech and language assessments were conducted as part of the Pediatric HIV/AIDS Cohort Study Surveillance Monitoring of ART Toxicities study at ages 3 (N = 208) and 5 (N = 429) years. Domains of speech, overall language, vocabulary and grammar were assessed. SI and LI were defined by standardized scores

Background: Struma ovarii is a rare benign ovarian teratoma comprising of thyroid tissue. Infrequently, benign struma ovari can present with extra ovarian dissemination, thus posing a treatment challenge. Here we describe a case of peritoneal strumosis treated with thyroidectomy and two courses of radioiodine ablation. Case presentation: 70 year old female with history of bilateral salphingo-oophorectomy 30 years prior presented with elevated thyroglobulin levels. Computed Tomography of the chest, abdomen and pelvis showed multiple peritoneal lesions. Subsequent biopsy revealed benign thyroid tissue. Thyroidectomy revealed papillary thyroid carcinoma; however, it did not match the peritoneal lesions. She was subsequently treated with radioiodine in two doses, each 30 mCi, 20 months apart. Follow up imaging and thyroglobulin levels showed a significant response to radioactive iodine treatment. Conclusion: Peritoneal Strumosis is a rare presentation of extra ovarian struma ovarii with benign thyroid histology. We propose a treatment paradigm similar to a thyroid malignancy, including total thyroidectomy and radioactive ablation with I-131. Moreover, radioactive ablation can be performed in stages with smaller doses to avoid radiation-induced side effects with an excellent response. Keywords: Struma ovarii, Peritoneal strumosis, Radioiodine, Radioactive I-131, Thyroid, Thyroidectomy

Eosinophilic pancreatitis (EP) is reported in humans; however, the etiology and role of eosinophils in EP pathogenesis are poorly understood and not well explored. Therefore, it is interesting to examine the role of eosinophils in the initiation and progression of pancreatitis pathogenesis. Accordingly, we performed anti-major basic protein immunostaining, chloroacetate esterase, and Masson’s trichrome analyses to detect eosinophils, mast cells, and collagen in the tissue sections of mouse and human pancreas. Induced eosinophils accumulation and degranulation were observed in the tissue sections of human pancreatitis, compared with no eosinophils in the normal pancreatic tissue sections. Similarly, we observed induced tissue eosinophilia along with mast cells and acinar cells atrophy in cerulein-induced mouse model of chronic pancreatitis. Additionally, qPCR and ELISA analyses detected induced transcript and protein levels of proinflammatory and profibrotic cytokines, chemokines like IL 5, IL-18, eotaxin-1, eotaxin-2, TGF-β1, collagen-1, collagen-3, fibronectin, and α-SMA in experimental pancreatitis. Mechanistically, we show that eosinophil-deficient GATA1 and endogenous IL-5-deficient mice were protected from the induction of proinflammatory and profibrotic cytokines, chemokines, tissue eosinophilia, and mast cells in a cerulein-induced murine model of pancreatitis. These human and experimental data indicate that eosinophil accumulation and degranulation may have a critical role in promoting pancreatitis pathogenesis including fibrosis. Taken together, eosinophil tissue accumulation needs appropriate attention to understand and restrict the progression of pancreatitis pathogenesis in humans.NEW & NOTEWORTHY The present study for the first time shows that eosinophils accumulate in the pancreas and promote disease pathogenesis, including fibrosis in earlier reported cerulein-induced experimental models of pancreatitis. Importantly, we show that GATA-1 and IL-5 deficiency protects mice form the induction of eosinophil active chemokines, and profibrotic cytokines, including accumulation of tissue collagen in an experimental model of pancreatitis. Additionally, we state that cerulein-induced chronic pancreatitis is independent of blood eosinophilia.

Background Volumetric laser endomicroscopy (VLE) provides circumferential images 3 mm into the biliary and pancreatic ducts. We aimed to correlate VLE images with the normal and abnormal microstructure of these ducts. Methods: Samples from patients undergoing hepatic or pancreatic resection were evaluated. VLE images were collected using a low-profile VLE catheter inserted manually into the biliary and pancreatic ducts ex vivo. Histological correlation was assessed by two unblinded investigators. Results 25 patients (20 liver and 5 pancreatic samples) and 111 images were analyzed. VLE revealed three histological layers: epithelium, connective tissue, and parenchyma. It identified distinctive patterns for primary sclerosing cholangitis (PSC), pancreatic cysts, neuroendocrine tumor, and adenocarcinoma adjacent to the pancreatic duct or ampulla. VLE failed to identify dysplasia in a dominant stricture and inflammatory infiltrates in PSC. Reflectivity measurements of the liver parenchyma diagnosed liver cirrhosis with high sensitivity. Conclusions VLE can identify histological changes in the biliary and pancreatic ducts allowing real-time diagnosis. Further studies are needed to measure the accuracy of VLE in a larger sample and to validate our findings in vivo.

Interleukin (IL)-15 overexpression in eosinophilic gastrointestinal disorders is reported, but IL-15’s role in promoting eosinophilia gastroenteritis is largely unknown. Therefore, we generated enterocyte-overexpressed IL-15 transgenic mice using Fabpi-promoter. The Fabpi-IL-15 (iIL-15) transgenic mice show induced IL-15 levels in the jejunum with a marked increase in jejunum eosinophils. However, no induction of eosinophilia in the blood or any other gastrointestinal segment was observed. Eosinophilia in the jejunum villus was substantially higher in iIL-15 mice compared to wild type mice. In addition, goblet cell hyperplasia was also observed in the jejunum of iIL-15 mice. Furthermore, a significant correlation between induced IL-15 transcript and the IL-18 transcripts was observed. Therefore, to further understand the role of IL-18 in IL-15 mice associated gastrointestinal disorders; we generated iIL-15/IL-18Rα(−/−) mice. Using these mice, we found that IL-18 has an important role in promoting IL-15-induced eosinophilia. Since intestinal IL-15 overexpression is reported in food intolerance; we examined OVA intolerance in iIL-15 mice. The OVA-sensitized and challenged iIL-15 mice experienced weight loss, diarrhea, and eosinophilia in the jejunum. Taken together, our findings demonstrate that intestinal IL-15 overexpression induces IL-18-dependent eosinophilia and immunoglobulin in the intestine that promotes food allergic responses.

Worldwide increase incidences of allergic diseases have heightened the interest of clinicians and researchers to understand the role of neuroendocrine cells in the recruitment and activation of inflammatory cells. Several pieces of evidence revealed the association of neuropeptides in the pathogenesis of allergic diseases. Importantly, one such peptide that is secreted by neuronal cells and immune cells exerts a wide spectrum of immunological functions as cytokine/chemokine is termed as Vasoactive Intestinal Peptide (VIP). VIP mediates immunological function through interaction with specific receptors namely VPAC-1, VPAC-2, CRTH2 and PAC1 that are expressed on several immune cells such as eosinophils, mast cells, neutrophils, and lymphocytes; therefore, provide the basis for the action of VIP on the immune system. Additionally, VIP mediated action varies according to target organ depending upon the presence of specific VIP associated receptor, involved immune cells and the microenvironment of the organ. Herein, we present an integrative review of the current understanding on the role of VIP and associated receptors in allergic diseases, the presence of VIP receptors on various immune cells with particular emphasis on the role of VIP in the pathogenesis of allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis. Being crucial signal molecule of the neuroendocrine-immune network, the development of stable VIP analogue and/or antagonist may provide the future therapeutic drug alternative for the better treatment of these allergic diseases. Taken together, our current review summarizes the current understandings of VIP biology and further explore the significance of neuroendocrine cells derived VIP in the recruitment of inflammatory cells in allergic diseases that may be helpful to the investigators for planning the experiments and accordingly predicting new therapeutic strategies for combating allergic diseases. Summarized graphical abstract will help the readers to understand the significance of VIP in allergic diseases.

Background: Rhino-orbital-cerebral mucormycosis has reached epidemic proportion during second wave of COVID-19 pandemic in India. In this study we aimed to understand the demographics, presentation, temporal sequence, risk factors and outcomes to undertake measures for prevention and treatment and benefit of administering liposomal amphotericin via retrobulbar injection in addition to systemic antifungals in the setting of rhino-orbital-mucormycosis. Methods: Study of patients with COVID-19-associated mucormycosis managed or co-managed by ophthalmologists in our centre from April 2021 to June 2021. Results: Male predominance and more than 75% associated with COVID-19 infection. Common risk factors associated were DM and corticosteroids use. Unilateral involvement was common (82.4%). Most common primary symptom and sign of ROCM is orbital/facial pain (68.4%) and ptosis (84.2 %) respectively. retro bulbar amphotericin B injections had slight improvement in vision (25%), ptosis (37.5%) and extra ocular movement (25%) with few complications. Surgical management were PNS debridement (42.1%), exenteration added in 17.5 % and with above procedure additional maxillectomy needed in 14%. 22.8 % cases were succumbed by disease while 40.1 % of live patients needed orbital exenteration. Conclusions: ROCM has visible signs and symptoms, help us in early diagnosis as compared to mucormycosis at other anatomical sites and should be known to all ophthalmologists. Early diagnosis by involving root level health worker and creation of standard treatment guideline on emerging heath problem is an urgent need.

Food allergy, a commonly increasing problem worldwide, defined as an adverse immune response to food. A variety of immune-related effector cells such as mast cells, eosinophils, neutrophils, and T cells are involved in food-related allergic responses categorized as IgE-mediated, non-IgE mediated, and mixed (IgE and non-IgE) depending upon underlying immunological mechanisms. The dietary antigens mainly target the gastrointestinal tract including pancreas that gets inflamed due to food allergy and leads acute pancreatitis. Reports indicate several food proteins induce pancreatitis; however, detailed underlying mechanism of food-induced pancreatitis is unexplored. The aim of the review is to understand and update the current scenario of food-induced pancreatitis. A comprehensive literature search of relevant research articles has been performed through PubMed and articles were chosen based on their relevance to food allergen mediated pancreatitis. Several cases in the literature indicating that acute pancreatitis has been provoked after the consumption of mustard, milk, egg, banana, fish, and kiwi fruits. Food-induced pancreatitis is an ignored and unexplored area of research. The review highlights the significance of food in the development of pancreatitis and draws the attention of physicians and scientists to consider food allergies as a possible cause for initiation of pancreatitis pathogenesis.

Low-grade dysplasia (LGD) is a risk factor for progression in Barrett's esophagus (BE). Progression estimates however vary and predictors of progression are not well established. We aimed to assess predictors of progression in a multicenter BE-LGD cohort.All subjects with LGD (diagnosed by a GI pathologist) in a prospective BE registry were identified. Progression was defined development of HGD/EAC more than 12 months after index date of LGD diagnosis. Clinical, endoscopic factors and impact of histologic review by an independent panel of two GI pathologists were assessed as predictors of progression. Cox proportional hazard models were used to assess their association with risk of progression.244 BE-LGD subjects met inclusion criteria. Their mean age was 63.2 years. 205 (84%) were males. The median follow up was 4.8 years. Fifty six patients were diagnosed with HGD/EAC in less than 12 months, while 14 progressed to HGD/EAC after 12 months, with an overall annual risk of progression of 1.2%. 29% of LGD subjects were downgraded to non-dysplastic and the remaining re-confirmed as LGD or indefinite dysplasia. The risk of progression in the reconfirmed LGD group was eight fold higher (hazards ratio: 7.6, 95% CI: 1.5-139.4) in a propensity score stratified model.In this large BE-LGD cohort, progression risk increased substantially when an additional panel of two expert GI pathologists re-confirmed a LGD diagnosis. These BE subjects may be candidates for endoscopic therapy. LGD was a marker of prevalent HGD/EAC in 18% of patients.

Sessile serrated adenomas/polyps (SSA/P) are an under-recognized disease with a unique malignant pathway. Improved endoscopic recognition and pathological interpretation is needed. To determine whether an educational intervention that improved adenoma detection rate (ADR) could improve SSA/P detection rate after reclassification of previously termed “hyperplastic” polyps. We reanalyzed data from a prospective randomized trial of an educational intervention aimed at increasing ADR. All hyperplastic polyps ≥6 mm reported in a previously published study were rereviewed and reclassified using standardized criteria for serrated lesions. Detection rates of sessile serrated adenomas/polyps and other clinically relevant serrated polyps were calculated in the baseline and post-training phases of the original study. Of 263 available for rereview, 33 (12.5%) were reclassified as SSA/P (N = 32) or traditional serrated adenoma (TSA) (N = 1). Reclassification was more common in the right colon (18 vs. 8%, p = 0.02). Baseline SSA/P detection rate was 0.7% in the untrained group and 1.3% in the trained group. Post-training, the SSA/P detection rate increased to 2.1 and 1.5%, respectively. The clinically relevant serrated polyp detection rate at baseline was 14.2% in the untrained group and 11.3% in the trained group. After the educational intervention, the clinically relevant serrated polyp detection rates increased to 16.5 and 14.8% in the untrained and trained groups, respectively. The estimated odds of an endoscopist detecting either a SSA/P or other clinically relevant serrated polyp during colonoscopy increased by only 3% with the educational intervention (OR 1.03, 95% CI 0.61–1.74, p = 0.91). Pathological re-interpretation of larger serrated polyps resulted in the reclassification of 12.5% of lesions. Quality improvement methods focused on adenoma detection did not impact SSA/P detection, and thus specific methods for serrated polyp detection are needed.

Purpose: In patients with erectile dysfunction, it is important to differentiate psychogenic from organic causes. Penile Doppler ultrasonography is a relatively inexpensive and minimally invasive tool for this purpose. This study was conducted to evaluate the causes of erectile dysfunction in an adult male population, using penile Doppler ultrasonography. Materials and Methods: A retrospective study was conducted in a single center. All patients who presented with complaints of erectile dysfunction and underwent penile Doppler ultrasonography between July 2014 and June 2016 were included in this study. All examinations were performed using GE Voluson S6 and GE Logiq P5 devices. Following baseline scans, an intracavernosal injection of 20 μg of prostaglandin E1 was given. Peak systolic and end diastolic velocities were measured in each cavernosal artery. Patients with a peak systolic velocity of ＜25 cm/s were considered to have arterial insufficiency, while an end diastolic velocity of ＞5 cm/s was considered to indicate venous incompetence. Results: Out of 97 patients (mean age, 37.09±11.59 years; range, 19∼69 years), 50 patients (51.5%) had normal findings, 24 patients (24.7%) had arterial insufficiency, 15 patients (15.5%) had a venous leak, and 8 patients (8.2%) patients had arterial insufficiency with a venous leak. Psychogenic erectile dysfunction was significantly higher among patients aged ≤40 years, while arterial insufficiency with or without a venous leak was significantly higher among patients aged ＞40 years (p=0.022). Conclusions: A majority of the studied individuals demonstrated no organic cause of erectile dysfunction, thus confirming a high prevalence of the psychogenic etiology, particularly in relatively young individuals.

Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in promoting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways (i.e., Transforming growth factor-β/SMAD, mitogen-activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8 IL-10, IL-18, IL-33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for pancreatic pathogenesis.

Background and Objectives: Pancreatic cysts are evaluated by endoscopic ultrasound and fine needle aspiration (EUS). The only accepted treatment is pancreatectomy, which is associated with morbidity and mortality. This study evaluated the optimal thermal dosimetry of a novel radiofrequency ablation device using a standard electrosurgical unit in ex vivo cyst models. Methods: A modified EUS 22-gauge monopolar needle prototype with a tip electrode connected to a standard electrosurgical unit (Erbe USA, Marietta, GA, USA) was used to induce a subboiling point temperature. A cyst model was created using 2-cm sections of porcine small intestine ligated and filled with saline. After ablation, the cyst models were prepared for pathological evaluation. The epithelial layers were measured in at least two different sites with a micrometer and compared with the corresponding control sample. Results: Thirty-two cyst models were ablated with maximum temperatures of 50°C, 60°C, 90°C, and 97°C in 8, 11, 11, and 2 cysts, respectively. Longer ablation times were required to induce higher temperatures. A trend in the reduction in thickness of the measured layers was observed after exposure to higher temperatures. A temperature over 50°C was required for the ablation of the muscularis, submucosa, and villi, and over 60°C was required to ablate the mucosal crypts. Conclusions: In a preclinical model, a novel radiofrequency EUS-capable needle connected to a standard electrosurgical unit using standard low-voltage coagulation provided ablation in a temperature-dependent fashion with a threshold of at least 60°C and a safe cyst margin below 97°C. This potentially will allow low-cost, convenient cyst ablation.

BACKGROUND Language impairment (LI) risk is increased for perinatally acquired human immunodeficiency virus-infected (PHIV) and perinatally exposed to HIV but uninfected (PHEU) youth. This study evaluates the persistence of LI in these groups. METHODS The Clinical Evaluation of Language Fundamentals was repeated on participants of the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol 18 months postbaseline. Regression models identified factors associated with change in standardized score (SC) and the resolution or development of LI. RESULTS Of 319 participants, 112 had LI at baseline. Upon re-evaluation, SCs were highly stable and changes were similar in PHIV (n = 212) and PHEU (n = 107) participants. Those with family history of language delays had a 2.39 point lower mean increase in SCs than those without, after controlling for demographic and socioeconomic factors and baseline LI status. Among PHIV participants, CD4 count

Objectives To estimate birth prevalence of congenital cytomegalovirus (cCMV) in HIV-exposed uninfected children born in the current era of combination antiretroviral therapy and describe cCMV-related neurodevelopmental and hearing outcomes. Study design The Surveillance Monitoring for ART Toxicities cohort study follows HIV-exposed uninfected children at 22 sites in the US and Puerto Rico. Birth cCMV prevalence was estimated in a subset of participants who had blood pellets collected within three weeks of birth and underwent ≥1 of 6 assessments evaluating cognitive and language development including an audiologic examination between 1 and 5 years of age. Detection of CMV DNA by polymerase chain reaction testing of peripheral blood mononuclear cells was used to diagnose cCMV. Proportions of suboptimal assessment scores were compared by cCMV status using Fisher exact test. Results Mothers of 895 eligible HIV-exposed uninfected children delivered between 2007 and 2015. Most (90%) were on combination antiretroviral therapy, 88% had an HIV viral load of ≤400 copies/mL, and 93% had CD4 cell counts of ≥200 cells/μL. Eight infants were diagnosed with cCMV, yielding an estimated prevalence of 0.89% (95% CI, 0.39%-1.75%). After adjusting for a sensitivity of 70%-75% for the testing method, projected prevalence was 1.2%-1.3%. No differences were observed in cognitive, language and hearing assessments by cCMV status. Conclusions Although birth cCMV prevalence in HIV-exposed uninfected children born to women with well-controlled HIV is trending down compared with earlier combination antiretroviral therapy-era estimates, it is above the 0.4% reported for the general US population. HIV-exposed uninfected children remain at increased risk for cCMV.

The aim of this module is to learn about the need for rights-based support services for children and families at risk in specific situations. It examines the concepts and theories of children in street situations, child substance abusers and children of substance abusers, children affected by HIV, children of incarcerated parents, and child-headed households. For each situation, the module facilitates learning to plan rights-based support services for these children, emphasising mobile services, drop-in day centres and temporary night shelters for street children; treatment of substance abuse; prevention, recovery and reintegration of HIV; prevention of stigmatization and discrimination against children of incarcerated parents; and designing an adult or organisation as the guardian of child-headed households.

Introduction Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is used for non-invasive staging and restaging of solid malignant tumors. PET-CT based criteria have been developed to evaluate the response to targeted therapy. These include the European Organization for Research and Treatment of Cancer (EORTC) and the PET Response Criteria in Solid Tumors (PERCIST). The aim of this study was to determine the agreement between EORTC and PERCIST criteria for treatment response evaluation in patients with solid malignant tumors. Materials and methods This was a retrospective study conducted from February 2017 till July 2017. Electronic medical records of patients diagnosed with solid malignant tumors were searched. Experienced radiologists evaluated the PET-CT images based on EORTC and PERCIST criteria. The Kappa (κ) test was used for evaluation of agreement between treatment response according to EORTC and PERCIST criteria. Results Out of 54 patients, 41 (75.9%) were male and 13 (24.1%) were female with a mean age of 57.09 ± 10.65 years. According to EORTC criteria, complete metabolic response (CMR) was seen in five (9.3%) of patients, partial metabolic response (PMR) was seen in 36 (66.7%) of patients, progressive metabolic disease (PMD) was seen in nine (16.7%) of patients and stable metabolic disease (SMD) was seen in four (7.4%) of patients. According to PERCIST criteria, CMR was seen in five (9.3%) of patients, PMR was seen in 33 (61.1%) of patients, PMD was seen in nine (16.7%) of patients and SMD was seen in seven (13.0%) of patients. EORTC and PERCIST agreed on 43 (79.6%) of the patients with κ-coefficient of 0.62 indicating good agreement (p-value of

Background & Aims Eosinophilic esophagitis (EoE) is assessed endoscopically (endoscopic activity), based on grades of edema, rings, exudates, furrows, and strictures (EREFS). We examined variations in endoscopic assessments of severity, developed and validated 3 EREFS-based scoring systems, and assessed responsiveness of these systems using data from a randomized placebo-controlled trial of patients with EoE. Methods For the development set, 5 gastroenterologists reviewed EREFS findings from 266 adults with EoE and provided endoscopist global assessment scores (EndoGA, scale of 0 to 10); variation (ΔEndoGA) was assessed using linear regression. We evaluated simple scores (features given arbitrary values from 0 to 3) and developed 2 scoring systems (adjusted score range, 0–100). We then fitted our linear regression model with mean EndoGA to data from 146 adults recruited in centers in Switzerland and the United States between April 2011 and December 2012. For the validation set, we collected data from 120 separate adults (recruited in centers in Switzerland and the United States between May 2013 and July 2014), assessing regression coefficient-based scores using Bland-Altman method. We assessed the responsiveness of our scoring systems using data from a randomized trial of patients with EoE given fluticasone (n=16) or placebo (n=8). Results The distribution of EndoGA values differed among endoscopists (mean ΔEndoGA, 2.6±1.8; range 0–6.6). We developed 2 regression-based scoring systems to assess overall and proximal and distal esophageal findings; variation in endoscopic features accounted for more than 90% of the mean EndoGA variation. In the validation group, differences between mean EndoGA and regression-based scores were small (ranging from –4.70 to 2.03), indicating good agreement. In analyses of data from the randomized trial, the baseline to end of study change in patients given fluticasone was a reduction of 24.3 in simple score (reduction of 4.6 in patients given placebo, P=.052); a reduction of 23.5 in regression-based overall score (reduction of 6.56 in patients given placebo, P=.12), and a reduction of 23.8 (reduction of 8.44 in patients given placebo, P=.11). Conclusion Assessments of endoscopic activity in patients with EoE vary among endoscopists. In an analysis of data from a randomized controlled trial, we found that newly developed scoring systems are no better than simple scoring system in detecting changes in endoscopic activity. These results support the use of a simple scoring system in evaluation of endoscopic activity in patients with EoE. clinicaltrials.gov no: NCT00939263 and NCT 01386112

For more than a century, the high occurrences of coronary and peripheral artery diseases in diabetes mellitus patients has been well recognised; despite that, the ability to improve CV event rates by optimizing glycaemic control has remained elusive. Nevertheless, the last decade has seen several cardiovascular outcome clinical trials (CVOTs) of many antihyperglycemic agents that reported promising results for cardiovascular and renal outcomes. This leads to a hot debate on the ideal drug choice for first-line treatment in T2DM. The purpose of this paper is to review the evidence supporting the use of metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors and incretin-based therapies for the management of individuals with T2DM and, discuss the rationale for selection.

BACKGROUND Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. METHODS In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. FINDINGS At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3·9 years (IQR 1·6-6·9) and 82 885 (88·8%) patients initiated NNRTI-based and 10 466 (11·2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9-52). 3883 (4·2%) patients switched to second-line ART after a median of 35 months (IQR 20-57) of ART. The cumulative incidence of switching at 3 years was 3·1% (95% CI 3·0-3·2), but this estimate varied widely depending on the cohort monitoring strategy, from 6·8% (6·5-7·2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0·8% (0·6-1·0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p

This chapter discusses a wide array of non-inflammatory bowel disease-type colitides, and includes both distinctive patterns of inflammation and injury, as well as etiologically specific entities. Histologic overlap between these entities requires careful consideration of clinical setting and the use of special stains when appropriate. The goal of assessment and reporting should be to either indicate an etiology or enable the clinician further investigate the multiple differential diagnoses based on the histology. Histologic evaluation should always be performed with the understanding that in certain unusual cases, a pattern resembling “colitis” may mask an underlying neoplastic condition.

Summary Background Studies describing intravascular involvement in Wilms tumor have focused on illustrating individual institutional experience and the elements of surgical management. Thrombus characteristics like extent, patterns of regression, and correlation with the surgical findings, intraluminal adhesion, and viable tumor in the thrombus, and patency of the inferior vena cava (IVC) have not been systematically described. Objectives The aim of this study is to evaluate these thrombus characteristics and explore their impact on the overall outcomes. Methods All patients with histologically confirmed Wilms tumors with intravascular thrombus diagnosed in the pediatric oncology unit of Tata Memorial Hospital registered from 2006 to 2019 were included. Data regarding clinical, radiological, and surgical particulars were retrieved from the prospectively maintained institutional database. Specific data for the thrombus included: distal extent before and after neoadjuvant chemotherapy, correlation of extent with the surgical findings, completeness of thrombectomy, the presence of a viable tumor in the thrombus, and the patency of the IVC. Survival analysis was performed utilizing the Kaplan–Meier method on SPSS software version 25. Results The study included 43 (9.9%) of the 432 patients with Wilms tumor having intravascular extension. Retrohepatic IVC (33.3%) followed by atrioventricular (26%) formed the frequent levels of thrombus with maximum regression occurring after chemotherapy in the latter (Summary figure). The overall concordance rate between computed tomography (CT) scan and surgical findings for the presence of thrombus was 86% and 4 patients had the thrombus limited to a lower level than the preoperative scan. At a median follow-up of 5-years, the 5-year event-free and overall survival was 81% and 82.2% respectively. Atrioventricular thrombus (p = 0.003) and postoperative patency of IVC (p = 0.02) were significantly associated with inferior survival, while the extent of regression, thrombus fracture, and viability was not significant. Discussion The findings of this study bring forth the characteristics of intravascular tumor thrombus affecting the outcomes which can be validated in future prospective studies. Although the ideal method for radiological assessment of the intravascular thrombus is elusive, CT scan provided adequate information for the presence and level of the intravascular thrombus with reasonable accuracy in this study. Study limitations include small sample size, the limited number of events, and lack of multivariate analysis to rule out confounding factors that could influence the observed findings. Conclusion Atrioventricular thrombus and occlusion of IVC represent adverse prognostic factors. The extent of regression, fracture, and viability of thrombus did not affect survival in this study. Download : Download high-res image (541KB) Download : Download full-size image Summary fig. . A collage of axial, coronal and sagittal computed tomogram images showing retrohepatic [A and A1], atrial [B and B1], ventricular [C and C1] thrombus.

Background: Perforating ocular injuries in particular carry a high risk of visual morbidity in all age groups. Risk factors associated with ocular trauma include gender, age, occupation, and lower socioeconomic status. Eye injuries are causing a major concern to the general ophthalmologists both in the developed and developing countries. Objective: The objective of this article is to study the profile of penetrating ocular injuries before and during the period of lockdown. Materials and Methods: A study was done to make a comparative analysis of the penetrating ocular injuries occurring during the period of lockdown of 3 months (April 1, 2020–June 30, 2020) and 3 months (January 1, 2020–March 31, 2020) before lockdown. Results: The study included 33 patients hospitalized before lockdown and 45 hospitalizations during the lockdown in all age groups. Injuries were more common in males. The injuries reported in the age group of 0–15 years before lockdown were 36.36% while during lockdown 60% injuries were observed. Modes of injuries reported before lockdown were indoor injuries (36.36%) and road traffic accidents (36.36%) while during lockdown, the major mode of injuries were indoor injuries (76.6%) whereas the road traffic accidents (10.0%) declined. Conclusion: During the lockdown, indoor injuries were more common in comparison to the outdoor injuries such as road traffic accidents, the latter being more prevalent before lockdown. During lockdown, increase in the indoor leisure activities of children led to a rise in the cases of eye injuries and an increase of almost double the number was observed. In addition to this, immobilization led to a decrease in the injuries due to road traffic accidents. The coronavirus disease-19 lockdown did have an impact on the profile of penetrating ocular injuries.

Hemangiopericytomas are tumors arising from the Zimmerman pericytes. They are characterized by their propensity to recur aggressively and metastasize. Surgery forms the primary treatment modality. Radiotherapy has been used in the postoperative setting and has proved to produce a significant progression-free survival in cases with residual disease. Radiotherapy has been applied even as a single modality treatment whenever surgery could not be performed. We are presenting four cases of meningeal hemangiopericytomas which have been treated with radiotherapy in combination with surgery. These cases show various scenarios in which Radiotherapy has been used in hemangiopericytoma: adjuvant setting, residual/recurrent setting, and in the palliative setting. As far as the technique is concerned, three-dimensional conformal radiotherapy, fractionated radiosurgery, and other forms of high-precision irradiation (intensity-modulated radiation therapy [IMRT]) were given.

Summary Background Due to increasing concerns about post-chikungunya (pCHIK) rheumatic disorders in Latin America we aimed to evaluate its occurrence in travelers returning to NYC from the Caribbean. Method Patients diagnosed with chikungunya (CHIK) during 2014 at the Bronx-Lebanon Hospital Center (Bronx, NewYork) were identified by reviewing laboratory and electronic medical records. Patients and caregivers of pediatric patients were interviewed by phone ≥9 months after the CHIK diagnosis to survey for chronic symptomatology and current health care needs. Reported chronic musculoskeletal complaints were categorized according to validated criteria. Results A total of 28 patients (54% females, median age [range] of 51.5 [0, 88] years) diagnosed with CHIK at our center were identified. Most (82%) had returned from the Dominican Republic. Nineteen (68%) patients were successfully contacted at a median (range) of 13 (9, 16) months since the acute diagnosis. A third (37%) reported ongoing complaints related to CHIK including joint pain (32%), muscle pain (32%), and joint swelling (26%). A presumptive diagnosis of pCHIK chronic inflammatory arthritis ( n = 4) and pCHIK musculoskeletal disorder ( n = 3) was established. Conclusions A third of travelers with CHIK acquired in the Caribbean may be at risk for developing persistent symptoms suggestive of pCHIK rheumatic disorder.

Aim: To evaluate the profile of strabismus and amblyopia in patients presenting to a tertiary care institution in order to understand the disease burden. Materials and Methods: A retrospective, prospective hospital-based observational study was conducted at a tertiary level eye care hospital in India. All patients with strabismus or amblyopia who presented over a 1-year period were identified and referred to the squint clinic, where they were evaluated with a detailed clinical history and examination. Results: A total of 24475 patients were evaluated, of which 1950 had strabismus or amblyopia. The overall magnitude of amblyopia and strabismus was 2.0% [95% confidence interval (CI), 1.8-2.2)] and 6.9% (95% CI, 6.6-7.2), respectively. About 20% of those seeking an ophthalmic consultation were children and they constituted over half of the population referred to the squint clinic. Among younger children, the burden of amblyopia and strabismus was 84.4% and 26.6%, respectively. Among the referred patients, strabismus was noted in 84.6% (N = 1649), most of the cases of which was of the comitant subtype (78.1%, N = 1288) with an equal distribution of exotropia and esotropia. Paralytic [12.9% (N = 251)] and restrictive [4.7% (N = 85)] squint constituted the remaining burden of strabismus. Conclusion: Strabismus and amblyopia affect a sizeable proportion of patients presenting to a tertiary care ophthalmology setup. A significantly higher burden is present in the pediatric population. The majority of the cases of strabismus are of a comitant variety, which do not merit tertiary level eye care. There is a need to improve pediatric eye care at a secondary level to reduce the immense burden on tertiary referral centers.

Sulfiredoxin (SRXN1/Srx) is a multifunction enzyme with a primary antioxidant role of reducing the overoxidized inactive form of peroxiredoxins (Prxs). The function and mechanisms of Srx in cancer development are not well understood. Here, Srx is preferentially expressed in human colorectal cancer cells but not in normal colon epithelial cells. Loss-of-function studies demonstrate that knockdown of Srx in poorly differentiated colorectal cancer cells not only leads to the inhibition of colony formation and cell invasion in vitro, but also reduces tumor xenograft growth and represses metastasis to distal organs in a mouse orthotopic implantation model. Notably, exactly opposite effects were observed in gain-of-function experiments when Srx was ectopically expressed in well-differentiated colorectal cancer cells. Mechanistically, expression of Srx enhances the activation of MAPK signaling through increasing the C-terminal tyrosine phosphorylation levels of EGFR. This function of Srx is mediated through its inhibition of EGFR acetylation at K1037, a novel posttranslational modification of EGFR in human colorectal cancer cells identified by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC/ESI/MS-MS) proteomic analysis. Furthermore, abolishment of K1037 acetylation in human colorectal cancer cells by site-specific mutagenesis leads to sustained activation of EGFR–MAPK signaling. Combined, these data reveal that Srx promotes colorectal cancer cell invasion and metastasis through a novel mechanism of enhancing EGFR signaling. Implications: Sulfiredoxin is a critical oncogenic protein that can be used as a molecular target to develop therapeutics for patients with metastatic colorectal cancer. Mol Cancer Res; 13(12); 1554–66. ©2015 AACR.

Background: Death from COVID-19 disproportionately affects men, with up to 80% of deaths in severe COVID-19 cases being in men. There are a number of potential differences that might contribute to these sex differences. TMPRSS2 is a serine protease that primes the spike protein of SARS-CoV-2, a critical step in viral entry. TMPRSS2 is most highly expressed in the prostate where it is under androgen control, upregulated by testosterone and downregulated by antiandrogens. ACE2, the receptor used for entry into the host cell, is located on the X chromosome and may also have levels that are altered by hormones, with estradiol downregulating its expression. Previous research on acute lung injury demonstrated that estradiol seems to have beneficial effects on repair of lung injury. Therefore, our central hypothesis is that hormones may partially contribute to the gender disparity seen in COVID-19 patients, with high levels of testosterone being harmful and high levels of estrogen being helpful. Bicalutamide is a nonsteroidal antiandrogen that inhibits the action of androgens and, via feedback on the hypothalamic-pituitary axis, upregulates estradiol. We are conducting a phase II clinical trial to determine if bicalutamide improves the percentage of COVID+ patients with clinical improvement by 7 days. Methods: We will enroll 40 patients who are hospitalized for COVID-19 with minimal respiratory symptoms (respiratory rate Citation Format: Catherine H. Marshall, Srinivasan Yegnasubramanian, Hao Wang, Jennifer Durham, Ting Wang, Rachel Damico, Franco R. D'Alessio, Venkataramana K. Sidhaye, Andrew Pekosz, Joseph L. Mankowski, Sabra L. Klein, Sumati Murli, Elizabeth M. Jaffee, Samuel R. Denmeade. A phase II trial to promote recovery from COVID-19 with endocrine therapy [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr IA09.

Zhang et al recently described ACE2 expression along the GI tract and suggests the digestive system as a potential route for COVID-19.1 ACE2 is also expressed in the pancreas2 and lipase elevations, suggestive of pancreatic involvement, have been reported among patients with COVID-19.3 A recent case report4 demonstrated that severe pancreatitis may occur in COVID-19. However, the clinical implications of these findings with regards to COVID-19 susceptibility among patients with prior pancreatitis are unclear. In this retrospective study, we explored the prevalence, risk factors and outcomes of COVID-19 among patients with a history of pancreatitis. Consecutive patients whose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA testing was performed at Stanford between 4 March 2020, and 14 April 2020 (Institutional Review Board (IRB) protocol 55975) and had a history of acute (K85) or chronic pancreatitis (K86) were included. We performed univariate and multivariate logistic regression to determine …