Long-term outcome of anti-tumor necrosis factor alpha blockade in the treatment of juvenile spondyloarthritis.

OBJECTIVES: A significant proportion of patients with juvenile spondyloarthritis (JSpA) are refractory to treatment with established medications. The objective of this study was to assess long-term efficacy of treatment with anti-TNF agents in patients with JSpA. METHODS: An observational study of 16 patients with JSpA from 3 centres treated with infliximab (n=10) and etanercept (n=6) was performed, with a median follow-up period of 7.2 years. Prospective data was collected according to a standardized protocol. Outcomes examined were TEC, TAJC, markers of inflammation (ESR, CRP), functional assessments (C-HAQ, BASDAI, BASFI), and ongoing requirement for anti-TNF treatment. RESULTS: 13/16 patients (83%) had achieved clinical remission 6 months into the treatment. Improvement was sustained over time, with a median TAJC and TEC of 0 at any time point after 6 weeks. 6/16 patients (38%) showed a flare of arthritis after a median of 3.5 years. Two patients with hip disease prior to treatment required an arthroplasty 3 and 8 years post anti-TNF initiation. Patients showed progression of sacroiliitis with median modified New York score of 1 (range 0-3) at time of diagnosis and 3 (range 0-4) at last follow-up (p=0.002). Median BASDAI at last follow up was 1.6, median BASFI 3.1. Two patients developed transient reactions (one generalised, one local); no patient developed other adverse effects during the study. CONCLUSIONS: Anti-TNF treatment in JSpA refractory to standard treatment results in good long-term disease control except for pre-existing hip disease. However, radiographic evidence suggests inferior efficacy for control of sacroiliac joint disease.

Physiological changes in the size of the septal swell body correlate with changes in inferior turbinate size.

OBJECTIVE: The nasal septal swell body is a normal anatomical structure located in the superior nasal septum anterior to the middle turbinate. However, the impact of the septal swell body in nasal breathing during normal function and disease remains unclear. This study aimed to establish that the septal swell body varies in size over time and correlates this with the natural variation of the inferior turbinates. METHOD: Consecutive patients who underwent at least two computed tomography scans were identified. The width and height of the septal swell body and the inferior turbinates was recorded. A correlation between the difference in septal swell body and turbinates between the two scans was performed using a Pearson's coefficient. RESULTS: A total of 34 patients (53 per cent female with a mean age of 58.3 ± 20.2 years) were included. The mean and mean difference in septal swell body width between scans for the same patient was 1.57 ± 1.00 mm. The mean difference in turbinate width between scans was 2.23 ± 2.52 mm. A statistically significant correlation was identified between the difference in septal swell body and total turbinate width (r = 0.35, p = 0.04). CONCLUSION: The septal swell body is a dynamic structure that varies in width over time in close correlation to the inferior turbinates. Further research is required to quantify its relevance as a surgical area of interest.

An artificial intelligence algorithm that identifies middle turbinate pneumatisation (concha bullosa) on sinus computed tomography scans.

OBJECTIVE: Convolutional neural networks are a subclass of deep learning or artificial intelligence that are predominantly used for image analysis and classification. This proof-of-concept study attempts to train a convolutional neural network algorithm that can reliably determine if the middle turbinate is pneumatised (concha bullosa) on coronal sinus computed tomography images. METHOD: Consecutive high-resolution computed tomography scans of the paranasal sinuses were retrospectively collected between January 2016 and December 2018 at a tertiary rhinology hospital in Australia. The classification layer of Inception-V3 was retrained in Python using a transfer learning method to interpret the computed tomography images. Segmentation analysis was also performed in an attempt to increase diagnostic accuracy. RESULTS: The trained convolutional neural network was found to have diagnostic accuracy of 81 per cent (95 per cent confidence interval: 73.0-89.0 per cent) with an area under the curve of 0.93. CONCLUSION: A trained convolutional neural network algorithm appears to successfully identify pneumatisation of the middle turbinate with high accuracy. Further studies can be pursued to test its ability in other clinically important anatomical variants in otolaryngology and rhinology.

An artificial intelligence algorithm that differentiates anterior ethmoidal artery location on sinus computed tomography scans.

OBJECTIVE: Deep learning using convolutional neural networks represents a form of artificial intelligence where computers recognise patterns and make predictions based upon provided datasets. This study aimed to determine if a convolutional neural network could be trained to differentiate the location of the anterior ethmoidal artery as either adhered to the skull base or within a bone 'mesentery' on sinus computed tomography scans. METHODS: Coronal sinus computed tomography scans were reviewed by two otolaryngology residents for anterior ethmoidal artery location and used as data for the Google Inception-V3 convolutional neural network base. The classification layer of Inception-V3 was retrained in Python (programming language software) using a transfer learning method to interpret the computed tomography images. RESULTS: A total of 675 images from 388 patients were used to train the convolutional neural network. A further 197 unique images were used to test the algorithm; this yielded a total accuracy of 82.7 per cent (95 per cent confidence interval = 77.7-87.8), kappa statistic of 0.62 and area under the curve of 0.86. CONCLUSION: Convolutional neural networks demonstrate promise in identifying clinically important structures in functional endoscopic sinus surgery, such as anterior ethmoidal artery location on pre-operative sinus computed tomography.

Effect of methylprednisolone on small bowel, spleen and liver changes in a murine model of inflammatory bowel disease.

The aim of this study was to evaluate the influence of methylprednisolone (1 mg/kg, i.p.) on inflammatory lesions in the small bowel, liver (pericholangitis) and spleen (lymphofollicular proliferation), in a model of inflammatory bowel disease induced by 2.4-dinitrofluorobenzene in previously sensitized BALB-c mice. As a parameter of corticosteroid anti-inflammatory and immunosuppressive action, we simultaneously investigated its effects on mononuclear cell accumulation within the ileal lamina propria and submucosa during the observed time period (1-30 days). We noted a significant decrease in accumulation of mononuclear cells within the lamina propria (P < 0.001). An effect on mononuclear cell infiltration within the ileal submucosa was also noted but was not statistically significant. In addition, pericholangitis in the liver and lymphofollicular proliferation in the spleen were not observed in the experimental group during treatment with methylprednisolone. The results of this study indicate that the previously described model of intestinal inflammation could be used in further research of present and new therapeutic modalities for inflammatory bowel disease.

A new gastric juice peptide, BPC. An overview of the stomach-stress-organoprotection hypothesis and beneficial effects of BPC.

The possibility that the stomach, affected by general stress, might initiate a counter-response has not until recently been considered in theories of stress. We suggest that the stomach, as the most sensitive part of the gastrointestinal tract and the largest neuroendocrine organ in the body, is crucial for the initiation of a full stress response against all noxious stress pathology. The end result would be a strong protection of all organs invaded by 'stress'. Consistent with this assumption, this coping response is best explained in terms of 'organoprotection'. Endogenous organoprotectors (eg prostaglandins, somatostatin, dopamine) are proposed as mediators. Such an endogenous counteraction could even be afforded by their suitable application. A new gastric juice peptide, M(r) 40,000, named BPC, was recently isolated. Herein, a 15 amino acid fragment (BPC 157), thought to be essential for its activity, has been fully characterized and investigated. As has been demonstrated for many organoprotective agents using different models of various tissue lesions, despite the poorly understood final mechanism, practically all organ systems appear to benefit from BPC activity. These effects have been achieved in many species using very low dosages (mostly microgram and ng/kg range) after ip, ig, and intramucosal (local) application. The effect was apparent already after one application. Long lasting activity was also demonstrated. BPC was highly effective when applied simultaneously with noxious agents or in already pathological, as well as chronical, conditions. Therefore, it seems that BPC treatment does not share any of the so far known limitations for 'conventional organoprotectors'. No influence on different basal parameters and no toxicity were observed. These findings provide a breakthrough in stress theory. BPC, as a possible endogenous free radical scavenger and organoprotection mediator, could be a useful prototype of a new class of drugs, organoprotective agents.

Hepatoprotective effect of BPC 157, a 15-amino acid peptide, on liver lesions induced by either restraint stress or bile duct and hepatic artery ligation or CCl4 administration. A comparative study with dopamine agonists and somatostatin.

The hepatoprotective effects of a newly synthesized 15 amino acid fragment code named BPC 157 was evaluated in comparison with the reference standards (bromocriptine, amantadine and somatostatin) in various experimental models of liver injury in rats: 24 h-bile duct+hepatic artery ligation 48 h-restraint stress and CCl4 administration. BPC 157 administered either intragastrically or intraperitoneally, significantly prevented the development of liver necrosis or fatty changes in rats subjected to 24 h bile duct + hepatic artery ligation, 48 h-restraint stress, CCl4 treatment (1 ml/kg i.p., sacrifice 48 h thereafter). The other reference drugs had either little or no protective actions in these models. Noteworthy, the laboratory test results for bilirubin, SGOT, SGPT fully correlated with the macro/microscopical findings. Thus, on the basis of consistent protective effect of BPC 157, possible clinical application in liver diseases is now warranted.

The beneficial effect of BPC 157, a 15 amino acid peptide BPC fragment, on gastric and duodenal lesions induced by restraint stress, cysteamine and 96% ethanol in rats. A comparative study with H2 receptor antagonists, dopamine promotors and gut peptides.

The protection of stomach and duodenum in conjecture with anti-inflammatory effect was demonstrated for a novel 15 amino acid peptide, coded BPC 157, a fragment of the recently discovered gastric juice peptide BPC. BPC 157 (i.p./i.g.) was investigated in rats in comparison with several reference standards in three experimental ulcer models (48 h-restraint stress, subcutaneous cysteamine, intragastrical 96% ethanol ulcer tests) (pre-/co-/post-treatment). Only BPC 157 regimens were consistently effective in all of the tested models. On the other hand, bromocriptine, amantadine, famotidine, cimetidine and somatostatin were ineffective (restraint stress). A dose-dependent protection (cysteamine) and/or partial positive effect (related to treatment conditions) (ethanol), was obtained with glucagon, NPY and secretin whereas CCK/26-30/was not effective. Based on Monastral blue studies BPC 157 beneficial effect appears to be related to a strong endothelial protection.

Perforation--a rare complication of a small-bowel carcinoid.

Carcinoids are rare compared to other tumours of the gastrointestinal tract, but present a significant portion of tumours of the small intestine. The case of a 50-year-old man who suffered perforation of a small-bowel carcinoid after failed diagnostic trials is reported here. Since intestinal perforation is rarely the first sign of the presence of a carcinoid, it is useful to bear this in mind when dealing with unclear pathological changes of the small intestine.

Factors predictive of the healing of pancreatic pseudocysts treated by percutaneous evacuation.

BACKGROUND/AIMS: Pseudocyst formation is a well-known complication of pancreatitis which develops over 1 to 4 weeks in approximately 15% of patients. Nearly one-third of pancreatic pseudocysts resolve spontaneously; however, if there is no resolution within six weeks, evacuation must be performed. The aim of this study was to prospectively assess the reliability of the following: etiology; location; amount of pseudocyst liquid; and concentrations of certain biochemical parameters (LDH, glucose, proteins, sodium, potassium, bilirubin, lipase and amylase) in the pseudocyst content and patients' serum, in terms of the efficacy of ultrasound-guided percutaneous evacuation as a therapeutic approach. METHODOLOGY: Pseudocyst fluid was obtained by ultrasound-guided percutaneous evacuation in 67 patients, with a history of pancreatitis and pancreatic pseudocysts larger than five centimeters in diameter, with a matured membraneous wall that persisted for more than six weeks. RESULTS: There is a prognostic value associated with the location of the pseudocyst, the amount of pseudocyst liquid and the concentration of proteins, potassium, lipase and amylase in the evacuated material. CONCLUSION: Analysis of the aforementioned parameters provides an early forecast of the outcome of percutaneous evacuation.

Hepatocyte growth factor levels in Croatian healthy and alcoholic liver cirrhosis patients.

Hepatocyte growth factor (HGF) is a most potent hepatocyte mitogen, and plays a mayor role in liver regeneration during injury. The aim of this study was to evaluate HGF values in Croatian healthy and alcoholic liver cirrhosis patients (AC). The HGF and standard laboratory tests of liver damage were measured in 33 AC patients, and 41 healthy subjects. HGF was measured by using an ELISA method. The HGF levels were higher in cirrhotic patients than in healthy subjects (median value is 0.78 vs. 0.19 ng/ml, p < 0.001). Japanese study showed similar values of HGF for healthy subjects and AC subjects. The HGF values in patients depend on grade of illness. There was found significant correlation between HGF and almost all standard liver damage tests. The ROC analysis showed that measuring of HGF had convincingly best accuracy than other parameters, and seems to be useful in classifying grade of illness.

Preoperative evaluation of rectal carcinoma by transrectal ultrasonography.

The aim of the study was to assess the diagnostic value of transrectal ultrasonography (TRUS) in detecting the depth of tumor infiltration as well as the involvement of lymph nodes in patients with rectal carcinoma diagnosed after rectoscopy and proven by examination of the biopsy specimen. TRUS was performed on thirty-three patients with rectal carcinoma prior to surgery, the first assessment of tumor growth, and extension by pathological examination of the operative specimen. TRUS correctly assessed perirectal growth in 18 out of 22 cases proven by pathology (two understaged, accuracy 86 percent), while in 12 cases with no perirectal growth proven by pathology this method was correct in 9 cases (three overstaged, accuracy 75 percent). The results of this study indicate that TRUS, combined with endoscopy and biopsy, is a useful procedure in the preoperative staging of malignant rectal lesions and provides valuable data for the therapeutic planning of patients with rectal carcinoma.

Giant peptic ulcers in patients undergoing maintenance hemodialysis.

The aim of the study was to investigate the clinical characteristics of hemodialyzed uremic patients with upper gastrointestinal lesions. A total of 20 (7.2%) out of 276 patients on hemodialysis program underwent endoscopy and rentgenography of the upper gastrointestinal tract. The incidence of peptic ulcer disease in the patients with end-stage renal disease was 4.3%. Six (30%) out of 20 uremic hemodialyzed patients with gastrointestinal complications had giant peptic ulcers of duodenum or prepyloric area. In three (50%) out of six subjects, giant peptic ulcers were located in the second portion of the duodenum. Gastrointestinal hemorrhagic complications occurred in 12 (60%) patients. The most frequent sources of bleeding were duodenal ulcers alone (8 patients) or in combination with gastric and/or duodenal flat erosions (6 patients), angiodysplasia of the duodenum (3 patients) and duodenal erosions (one patient). Two patients with bleeding from giant ulcers died from perforation and hemorrhagic shock. The uremic hemodialyzed patients with giant ulcers were older than 65, had higher basal gastrin concentration (305.3 +/- 183.8 pmol/l), and lower basal (1.6 +/- 0.16 mmol/h) and stimulated gastric acid secretion (14.4 +/- 8.63 mmol/h).

Tuberculous peritonitis--a case report.

Tuberculosis continues to be a major health problem worldwide and, due to its systemic nature, its clinical presentation may be highly variable. The diagnosis may, therefore, be unduly delayed. A 67-year old male refugee was admitted to our Department with a diagnosis of intra-abdominal carcinomatosis. During hospitalization, tuberculous peritonitis was found to be the cause of his symptoms. Antituberculosis therapy was administered and the patient responded adequately, achieving total clinical remission. The importance of considering this polymorphous disease is emphasized.

Whipple's disease: a case study with unexpected prognosis.

Due to the systemic nature of Whipple's disease, its clinical presentation may be highly variable. The diagnosis may, therefore, be unduly delayed. Untreated, Whipple's disease is still potentially lethal. Although it traditionally presents with signs and symptoms of small intestine involvement, such as diarrhea and malabsorption, Whipple's disease can involve many other organs. Typically, the diagnosis is established by biopsy of the small intestine. The authors describe a case of Whipple's disease in order to stress the importance of bearing this polymorphic disease in mind, with special emphasis on its possible lethal outcome in spite of therapy.

The dynamics of endogenous zinc in different animal models of gastroduodenal ulceration.

The body possesses many various endogenous substances that enable it to protect itself from various noxious events. One of the nonspecific reactions is the increase of endogenous zinc concentrations in various tissues. The aim of this study was to focus on the changes of zinc serum and tissue concentrations in well-established models of gastric (24 h restraint stress and 5 min ethanol) and duodenal ulceration (24 h cysteamine). Ten female Wistar rats, weighing 180-250 g were used in each of the experimental groups. Upon sacrificing, the ulcer index was recorded. Zinc serum and tissue concentrations were determined using atomic absorption spectrophotometry. Ten unstressed animals served as a healthy control group. The results of our study clearly indicated certain changes in serum zinc in all these ulcer models. Changes in tissue concentrations, varying from model to model, were also observed. In conclusion, all this data confirm the fact that endogenous zinc represents a natural line of the body's defense system when exposed to stress.

Use of octreotide-acetate in preventing pancreatitis-like changes following therapeutic endoscopic retrograde cholangiopancreatography.

Acute pancreatitis is a serious complication of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterectomy (EST). In addition, serum pancreatic enzymes increase without clinical symptoms in up to 75% of patients undergoing endoscopic procedures. The aim of this trial was to investigate the effects of octreotide in the prevention of these possible complications in patients undergoing therapeutic ERCP. The study was carried out in 209 subjects who were randomly allocated to two groups (A and B). Group A received 0.5 mg of octreotide-acetate subcutaneously one hour prior to ERCP; group B was given placebo. Serum amylase and lipase values were measured before premedication and 1.5, 2, 6 and 24 hours following endoscopy. Following ERCP, the increase in both amylase and lipase values was significantly greater in the control (placebo) group, but this significance disappeared 24 hours following the procedure. Symptoms of acute pancreatitis developed in 4 (3.85%) patients who were given octreotide-acetate, compared to 10 (9.52%) patients in the control group. The results obtained in our study seem to indicate that octreotide could prevent the increase in serum pancreatic enzymes, but no significant difference was observed in the prevention of post-ERCP pancreatitis.

[New findings in the etiopathogenesis of ulcers and reevaluation of therapy]. / Bitne novosti u etiopatogenezi ulkusa i reevaluacija terapije.

The etiopathogenesis of ulcer disease is comprehensive and many experimental and clinical data failed to prove the primary cause of the disease. Although much has been learned concerning the pathophysiological mechanism which appear important in the development of ulcer disease, our present knowledge of the etiology of this disease is incomplete. Depression of the gastric acid secretion still remains the main treatment approach, although the cytoprotective drugs are interesting therapeutic challenge. Etiology of the peptic ulcer disease is not solved yet, but the defense mechanisms of the gastric mucosa are much more clear what will lead to better understanding of the defense mechanisms in the gastric cancer. Omeprazole is an interesting new drug healing peptic ulcer in almost 100% of the patients. A philosophic question may be asked: "Do we need to know the etiology of the disease in order to be able to treat it properly?" Omeprazole heals the ulcer and, in fact, we do not know its etiology. In the cost-benefit ratio, the most widely used drugs are still H2-receptor antagonists and sucralfate, and omeprazole is reserved for the patients with resistant ulcer disease, Zollinger-Ellison syndrome and severe reflux esophagitis.

[An approach to dyspepsia in primary health care]. / Pristup dispepsiji u primarnoj zdravstvenoj zastiti.

Dyspepsia is a common problem in primary health care and involves a great deal of physician's time, if we assume that the prevalence in general population is 25-50%. Since the definition of dyspepsia has been elusive, which has resulted in confusion about diagnosis and therapy, the need for management guidelines that would produce satisfactory results has been manifested. The International Gastro Primary Care Group has developed practical framework, which identifies the predominant symptom of dyspepsia as a guide in the selection of the most appropriate treatment, and is also used as a tool in dealing with common therapeutical dilemmas until new evidence become available.