EASY-APP: An artificial intelligence model and application for early and easy prediction of severity in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a potentially severe or even fatal inflammation of the pancreas. Early identification of patients at high risk for developing a severe course of the disease is crucial for preventing organ failure and death. Most of the former predictive scores require many parameters or at least 24 h to predict the severity; therefore, the early therapeutic window is often missed. METHODS: The early achievable severity index (EASY) is a multicentre, multinational, prospective and observational study (ISRCTN10525246). The predictions were made using machine learning models. We used the scikit-learn, xgboost and catboost Python packages for modelling. We evaluated our models using fourfold cross-validation, and the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and accuracy metrics were calculated on the union of the test sets of the cross-validation. The most critical factors and their contribution to the prediction were identified using a modern tool of explainable artificial intelligence called SHapley Additive exPlanations (SHAP). RESULTS: The prediction model was based on an international cohort of 1184 patients and a validation cohort of 3543 patients. The best performing model was an XGBoost classifier with an average AUC score of 0.81 ± 0.033 and an accuracy of 89.1%, and the model improved with experience. The six most influential features were the respiratory rate, body temperature, abdominal muscular reflex, gender, age and glucose level. Using the XGBoost machine learning algorithm for prediction, the SHAP values for the explanation and the bootstrapping method to estimate confidence, we developed a free and easy-to-use web application in the Streamlit Python-based framework (http://easy-app.org/). CONCLUSIONS: The EASY prediction score is a practical tool for identifying patients at high risk for severe AP within hours of hospital admission. The web application is available for clinicians and contributes to the improvement of the model.

The characteristics and prognostic role of acute abdominal on-admission pain in acute pancreatitis: A prospective cohort analysis of 1432 cases.

INTRODUCTION: Pain is the most common symptom in acute pancreatitis (AP) and is among the diagnostic criteria. Therefore, we aimed to characterize acute abdominal pain in AP. METHODS: The Hungarian Pancreatic Study Group prospectively collected multicentre clinical data on 1435 adult AP patients between 2012 and 2017. Pain was characterized by its intensity (mild or intense), duration prior to admission (hours), localization (nine regions of the abdomen) and type (sharp, dull or cramping). RESULTS: 97.3% of patients (n = 1394) had pain on admission. Of the initial population with acute abdominal pain, 727 patients answered questions about pain intensity, 1148 about pain type, 1134 about pain localization and 1202 about pain duration. Pain was mostly intense (70%, n = 511/727), characterized by cramping (61%, n = 705/1148), mostly starting less than 24 h prior to admission (56.7%, n = 682/1202). Interestingly, 50.9% of the patients (n = 577/1134) had atypical pain, which means pain other than epigastric or belt-like upper abdominal pain. We observed a higher proportion of peripancreatic fluid collection (19.5% vs. 11.0%; p = 0.009) and oedematous pancreas (8.4% vs. 3.1%; p = 0.016) with intense pain. Sharp pain was associated with AP severity (OR = 2.481 95% CI: 1.550-3.969) and increased mortality (OR = 2.263, 95% CI: 1.199-4.059) compared to other types. Longstanding pain (>72 h) on admission was not associated with outcomes. Pain characteristics showed little association with the patient's baseline characteristics. CONCLUSION: A comprehensive patient interview should include questions about pain characteristics, including pain type. Patients with sharp and intense pain might need special monitoring and tailored pain management. SIGNIFICANCE: Acute abdominal pain is the leading presenting symptom in acute pancreatitis; however, we currently lack specific guidelines for pain assessment and management. In our cohort analysis, intense and sharp pain on admission was associated with higher odds for severe AP and several systemic and local complications. Therefore, a comprehensive patient interview should include questions about pain characteristics and patients with intense and sharp pain might need closer monitoring.

Glucose levels show independent and dose-dependent association with worsening acute pancreatitis outcomes: Post-hoc analysis of a prospective, international cohort of 2250 acute pancreatitis cases.

BACKGROUND: Metabolic risk factors, such as obesity, hypertension, and hyperlipidemia are independent risk factors for the development of various complications in acute pancreatitis (AP). Hypertriglyceridemia dose-dependently elicits pancreatotoxicity and worsens the outcomes of AP. The role of hyperglycemia, as a toxic metabolic factor in the clinical course of AP, has not been examined yet. METHODS: We analyzed a prospective, international cohort of 2250 AP patients, examining associations between (1) glycosylated hemoglobin (HbA1c), (2) on-admission glucose, (3) peak in-hospital glucose and clinically important outcomes (mortality, severity, complications, length of hospitalization (LOH), maximal C-reactive protein (CRP)). We conducted a binary logistic regression accounting for age, gender, etiology, diabetes, and our examined variables. Receiver Operating Characteristic Curve (ROC) was applied to detect the diagnostic accuracy of the three variables. RESULTS: Both on-admission and peak serum glucose are independently associated with AP severity and mortality, accounting for age, gender, known diabetes and AP etiology. They show a dose-dependent association with severity (p < 0.001 in both), mortality (p < 0.001), LOH (p < 0.001), maximal CRP (p < 0.001), systemic (p < 0.001) and local complications (p < 0.001). Patients with peak glucose >7 mmol/l had a 15 times higher odds for severe AP and a five times higher odds for mortality. We found a trend of increasing HbA1c with increasing LOH (p < 0.001), severity and local complications. CONCLUSIONS: On-admission and peak in-hospital glucose are independently and dose-dependently associated with increasing AP severity and mortality. In-hospital laboratory control of glucose and adequate treatment of hyperglycemia are crucial in the management of AP.

IMAT-IGRT Treatment with Simultaneous Integrated Boost as Dose Escalation for Patients with Cervical Cancer: A Single Institution, Prospective Pilot Study.

Purpose: The aim of this study was to introduce the simultaneous integrated boost (SIB) technique to assess the safety of replacement of the brachytherapy (BT) boost for ineligible patients with cervical cancer receiving radiochemotherapy (RCT). Methods: Fourteen patients were enrolled between 2015 and 2018. SIB was delivered using RapidArc technique at doses of 2.4 Gy per fraction during pelvic irradiation with 50.4/1.8 Gy in seven patients (to a total dose of 67.2 Gy) with limited volume disease. In 7 patients with a more advanced disease stage (>5 cm tumor, parametric invasion both sides), parametric boost therapy was added to the pelvic radiotherapy to a total dose of the macroscopic tumor of 79.2 Gy. All patients received simultaneous cisplatin-based chemotherapy for 5 cycles with a dosage of 40 mg/m2. We examined acute toxicity (CTCAE v4.1) and quality of life (EORTC QLQ30 and CX24). The tumor regression rate was evaluated with RECIST 1.1 after the first 3- to 4-months follow-up Magnetic Resonance Imaging (MRI) scan. We calculated the percentage of tumor regression rate and the local control during the follow-up period and evaluated the survival data. Results: Our patient data are presented at a median follow-up time of 24.5 months. During the treatment period, no grade 3 to 4 toxicity was observed. During the follow-up period, no late-onset toxicity was observed. The tumor regression rate at the first MRI scan was 95.31% on average. Disease free survival (DFS) during the median follow-up of 24 months was 98.6%. Conclusion: In patients with cervical cancer, the SIB technique is amenable as part of definitive RCT. Dose escalation with the SIB technique can be safely administered to cervical cancer patients during definitive RCT if BT is not feasible. However, further randomized clinical studies are needed to validate the method, so routine use of it cannot be recommended yet.

LIFEStyle, Prevention and Risk of Acute PaNcreatitis (LIFESPAN): protocol of a multicentre and multinational observational case-control study.

INTRODUCTION: Acute pancreatitis (AP) is a life-threatening inflammatory disease of the exocrine pancreas which needs acute hospitalisation. Despite its importance, we have significant lack of knowledge whether the lifestyle factors elevate or decrease the risk of AP or influence the disease outcome. So far, no synthetising study has been carried out examining associations between socioeconomic factors, dietary habits, physical activity, chronic stress, sleep quality and AP. Accordingly, LIFESPAN identifies risk factors of acute pancreatitis and helps to prepare preventive recommendations for lifestyle elements. METHODS AND ANALYSIS: LIFESPAN is an observational, multicentre international case-control study. Participating subjects will create case and control groups. The study protocol was designed according to the SPIRIT guideline. Patients in the case group (n=1700) have suffered from AP (alcohol-induced, n=500; biliary, n=500; hypertriglyceridemiainduced, n=200; other, n=500); the control group subjects have no AP in their medical history. Our study will have three major control groups (n=2200): hospital-based (n=500), population-based (n=500) and aetiology-based (alcohol, n=500; biliary, n=500 and hypertriglyceridemia, n=200). All of them will be matched to the case group individually by gender, age and location of residence. Aggregately, 3900 subjects will be enrolled into the study. The study participants will complete a complex questionnaire with the help of a clinical research administrator/study nurse. Analysis methods include analysis of the continuous and categorical values. ETHICS AND DISSEMINATION: The study has obtained the relevant ethical approval (54175-2/2018/EKU) and also internationally registered (ISRCTN25940508). After obtaining the final conclusions, we will publish the data to the medical community and will also disseminate our results via open access. TRIAL REGISTRATION NUMBER: ISRCTN25940508; Pre-results.

Testicular torsion in a patient with Ehlers-Danlos syndrome.

We present a 19-year-old man with a diagnosis of Ehlers-Danlos syndrome (EDS) and a delayed presentation of testicular torsion. EDS is a rare and heterogeneous condition affecting collagen synthesis and presents multiple difficulties in a surgical setting. Management of this case of testicular torsion was complicated by impaired cognition of the patient, difficulty with intubation, a contralateral undescended testis and postoperative bleeding. We discuss the specific challenges faced in this case of testicular torsion with longstanding ischaemia and perioperative considerations of EDS.

Aging and Comorbidities in Acute Pancreatitis II.: A Cohort-Analysis of 1203 Prospectively Collected Cases.

Introduction: Our meta-analysis indicated that aging influences the outcomes of acute pancreatitis (AP), however, a potential role for comorbidities was implicated, as well. Here, we aimed to determine how age and comorbidities modify the outcomes in AP in a cohort-analysis of Hungarian AP cases. Materials and Methods: Data of patients diagnosed with AP by the revised Atlanta criteria were extracted from the Hungarian Registry for Pancreatic Patients. Outcomes of interest were mortality, severity, length of hospitalization, local, and systemic complications of AP. Comorbidities were measured by means of Charlson Comorbidity Index (CCI) covering pre-existing chronic conditions. Non-parametric univariate and multivariate statistics were used in statistical analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: A total of 1203 patients from 18 centers were included. Median age at admission was 58 years (range: 18-95 years), median CCI was 2 (range: 0-10). Only severe comorbidities (CCI ≥ 3) predicted mortality (OR = 4.48; CI: 1.57-12.80). Although severe comorbidities predicted AP severity (OR = 2.10, CI: 1.08-4.09), middle (35-64 years) and old age (≥65 years) were strong predictors with borderline significance, as well (OR = 7.40, CI: 0.99-55.31 and OR = 6.92, CI: 0.91-52.70, respectively). Similarly, middle and old age predicted a length of hospitalization ≥9 days. Interestingly, the middle-aged patients (35-64 years) were three times more likely to develop pancreatic necrosis than young adults (OR = 3.21, CI: 1.26-8.19), whereas the old-aged (≥65 years) were almost nine times more likely to develop systemic complications than young adults (OR = 8.93, CI: 1.20-66.80), though having severe comorbidities (CCI ≥ 3) was a predisposing factor, as well. Conclusion: Our results proved that both aging and comorbidities modify the outcomes of AP. Comorbidities determine mortality whereas both comorbidities and aging predict severity of AP. Regarding complications, middle-aged patients are the most likely to develop local complications; in contrast, those having severe comorbidities are prone to develop systemic complications. Studies validating the implementation of CCI-based predictive scores are awaited.

Histological diagnosis determines complications of percutaneous renal biopsy: a single-center experience in 353 patients.

BACKGROUND: We studied the connection between complication occurrence related to renal biopsies and histological diagnoses of the biopsy specimen. We also analyzed the distribution of diagnoses in our population. METHODS: We retrospectively studied 353 patients undergoing renal biopsy at the same center. Biopsies were performed after marking the site of puncture by ultrasound imaging. Connection of complications with diagnoses and clinical parameters was evaluated. RESULTS: Complication rate was 44.5% in our study. There was a significantly lower rate of complications in patients with diabetic nephropathy (likelihood ratio, LR = 0.44) or acute tubular necrosis (LR = 0.38), while patients with thin basement membrane syndrome had a more than 6-fold higher risk for development of intrarenal hemorrhage than others. Patients with vasculitis (LR = 2.88) and acute interstitial nephritis (LR = 3.18) have a more than doubled risk for arteriovenous shunts, while in patients with severe arteriosclerosis the prevalence of this complication was lower (LR = 0.46). Arteriovenous shunts developed also at a significantly higher rate in patients with rapidly progressive glomerulonephritis. CONCLUSION: Patients with thin basement membrane syndrome, vasculitis, rapidly progressive glomerulonephritis or acute interstitial nephritis should be observed more carefully after renal biopsy due to the significantly higher risk for certain complications.

Cigarette smoke elicits relaxation of renal arteries.

BACKGROUND: Epidemiological studies suggest that cigarette smoking - probably by eliciting hyperperfusion - increases glomerular filtration rate; thus, we hypothesized that cigarette smoke affects the vasomotor tone of renal arteries. MATERIALS AND METHODS: Acute changes in the resistance index of a segmental renal artery were measured in healthy individuals during smoking. In addition, the effects of water-soluble components of cigarette smoke on the isometric tension of isolated rat renal arteries were investigated in various conditions. RESULTS: In humans, cigarette smoking transiently reduced the resistance index of the renal artery segments (83·25 ± 5·67% of the baseline, P < 0·05). In the experimental model, water-soluble components of cigarette smoke (wCS) - either nicotinic or nicotine-free - elicited dose-dependent relaxations of rat isolated renal arteries (1% solution of nicotinic wCS: 41·18 ± 14·86% relaxation, 5% nicotinic wCS: 79·28 ± 8·91% relaxation, 10% nicotinic wCS 90·3 ± 6·1% relaxation, P < 0·05), which were not affected by removal of the endothelium, or by the soluble guanylate cyclase inhibitor oxadiazolo-quinoxalin-1, or the non specific potassium channel blocker tetraethylammonium, or the K(ATP) channel blocker glibenclamide. However, relaxations were reduced by catalase (1000 U mL⁻¹ catalase + 5% nicotinic wCS: 49·71 ± 18·4%, P < 0·05) and enhanced by superoxide dismutase (200 U mL⁻¹ SOD + 5% nicotinic wCS: 95·7 ± 2·3%, P < 0·05). CONCLUSIONS: On the basis of these findings, we propose that cigarette smoking could contribute to the increased glomerular filtration rate observed in healthy smokers. In addition, cigarette smoke via hydrogen peroxide mediation reduces vasomotor tone of renal arteries, which could lead to hyperperfusion of kidneys.

GCKR gene functional variants in type 2 diabetes and metabolic syndrome: do the rare variants associate with increased carotid intima-media thickness?

BACKGROUND: Recent studies revealed that glucokinase regulatory protein (GCKR) variants (rs780094 and rs1260326) are associated with serum triglycerides and plasma glucose levels. Here we analyzed primarily the association of these two variants with the lipid profile and plasma glucose levels in Hungarian subjects with type 2 diabetes mellitus and metabolic syndrome; and also correlated the genotypes with the carotid intima-media thickness records. METHODS: A total of 321 type 2 diabetic patients, 455 metabolic syndrome patients, and 172 healthy controls were genotyped by PCR-RFLP. RESULTS: Both GCKR variants were found to associate with serum triglycerides and with fasting plasma glucose. However, significant association with the development of type 2 diabetes mellitus and metabolic syndrome could not be observed. Analyzing the records of the patients, a positive association of prevalence the GCKR homozygous functional variants and carotid intima-media thickness was found in the metabolic syndrome patients. CONCLUSIONS: Our results support that rs780094 and rs1260326 functional variants of the GCKR gene are inversely associated with serum triglycerides and fasting plasma glucose levels, as it was already reported for diabetic and metabolic syndrome patients in some other populations. Besides this positive replication, as a novel feature, our preliminary findings also suggest a cardiovascular risk role of the GCKR minor allele carriage based on the carotid intima-media thickness association.

[Surgical treatment of primary leiomyosarcoma of the inferior vena cava]. / Primer vena cava inferior leiomyosarcoma (VCI-LMS) sebészi kezelése.

CASE REPORT: pLMS in the wall of the inferior vena cava is an extremely rare form of retroperitoneal malignancies. A case in a young female patient is presented; clinical symptoms, pre- and postoperative diagnosis and surgical treatment are discussed. A retroperitoneal mass detected by imaging was found to be a large tumor mass located at the middle segment of the IVC on exploration. The tumour was successfully excised and the IVC was reconstructed with a synthetic graft. Eight years later, this patient needed a repeat surgery due to local recurrence. This time tumour was attached to the left renal vein. A re-resection of the IVC was performed with subsequent synthetic graft reconstruction and the distal end of the left renal vein was reimplanted into a lower segment of IVC. DISCUSSION: Primary leiomyosarcoma of the inferior vena cava (pLMS-IVC) is an extremely rare form of retroperitoneal malignancies. The tumour arises from the medial layer of the venous wall and can grow either intraluminally, or extraluminally or in both directions, as well. It can be localized in the first segment of IVC (above the hepatic veins), in the second segment between hepatic and renal veins and finally in the third segment between the right common iliac vein and renal veins. Therefore, the tumour can infiltrate both hepatic and/or renal vessels. Upper segment tumours can cause Budd-Chiari syndrome (hepatomegaly, abdominal pain, jaundice and ascites) with a bad prognosis. Middle segment tumours usually present with right upper quadrant pain, or may mimic biliary tract disease with a much better prognosis. Accumulating experience suggests that radio-chemotherapy alone seems to be less effective than "en bloc" resection with clear margins including loco-regional lymph nodes. Therefore, our choice of treatment was the latter. Although radical resection can be carried out in most of cases, 50% of patients develop a late recurrence yet.