36 year old man presenting with pancreatitis and a history of recent commencement of orlistat case report

BACKGROUND: Orlistat is an anti-obesity drug licensed in the United Kingdom for 7 years. We present a case of a patient who developed pancreatitis four days after commencing orlistat. CASE PRESENTATION: A 36 year old man presented to hospital with acute severe pancreatitis four days after starting a course of Orlistat, a lipase inhibitor used in the treatment of obesity. A diagnosis of drug related pancreatitis was made by exclusion of other causes of pancreatitis; he was a teetotaller, had a normal serum calcium, had no family history of pancreatitis or hyperlipidaemia, no history of trauma and had no evidence of gallstones on Computerised Tomography scan (CT). CONCLUSION: Orlistat was the only drug that had been started recently and has been associated with pancreatitis previously. We found no case reports of similar cases, however 99 cases of orlistat related pancreatitis have been reported to the Food and Drug Administration (FDA), but no causative link has been found in clinical trials by the drug company. It is therefore not on the list of possible complications or side effects of the drug

A Dual-Beam Irradiation Facility for a Novel Hybrid Cancer Therapy

In this paper we present the main ideas and discuss both the feasibility and the conceptual design of a novel hybrid technique and equipment for an experimental cancer therapy based on the simultaneous and/or sequential application of two beams, namely a beam of neutrons and a CW (continuous wave) or intermittent sub-terahertz wave beam produced by a gyrotron for treatment of cancerous tumors. The main simulation tools for the development of the computer aided design (CAD) of the prospective experimental facility for clinical trials and study of such new medical technology are briefly reviewed. Some tasks for a further continuation of this feasibility analysis are formulated as well.Comment: 18 pages, 3 tables, 8 figures, 50 reference

Cost-effectiveness of CTA, MRA and DSA in patients with non-traumatic subarachnoid haemorrhage

OBJECTIVES: Intra-arterial digital subtraction angiography (DSA), magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) are imaging modalities used for diagnostic work-up of non-traumatic subarachnoid haemorrhage. The aim of our study was to compare the cost-effectiveness of MRA, DSA and CTA in the first year after the bleed. METHODS: A decision model was used to calculate costs and benefits (in quality-adjusted life-years [QALYs]) that accrued to cohorts of 1,000 patients. Costs and characteristics of diagnostic tests, therapy, patients’ quality of life and associated costs were respected. The diagnostic strategy with highest QALYs and lowest costs was considered most cost-effective. RESULTS: DSA was the most effective diagnostic option, yielding on average 0.6039 QALYs (95 % CI, 0.5761–0.6327) per patient, followed by CTA 0.5983 QALYs (95 % CI, 0.5704–0.6278) and MRA 0.5947 QALYs (95 % CI, 0.5674–0.6237). Cost was lowest for DSA (39,808 €; 95 % CI, 37,182–42,663), followed by CTA (40,748 €; 95 % CI, 37,937–43,831) and MRA (41,814 €; 95 % CI, 38,730–45,146). A strategy of CTA followed by DSA if CTA was negative or coiling deemed not feasible, was as effective as DSA alone at average costs of 39,767€ (95 % CI, 36,903–42,402). CONCLUSION: A combined strategy of CTA and DSA was found to be the most cost-effective diagnostic approach. MAIN MESSAGES: • We defined a standard model for cost-effectiveness analysis in diagnostic imaging. • Comparing total 1-year health costs and benefits, CTA is superior to MRA. • A strategy of combining CTA and DSA was found to be the most cost-effective diagnostic approach

Neoadjuvant Treatment for Resectable and Borderline Resectable Pancreatic Cancer:Chemotherapy or Chemoradiotherapy?

Worldwide, there is a shifting paradigm from immediate surgery with adjuvant treatment to a neoadjuvant approach for patients with resectable or borderline resectable pancreatic cancer (RPC or BRPC). Comparison of neoadjuvant and adjuvant studies is extremely difficult because of a great difference in patient selection. The evidence from randomized studies shows that overall survival by intention-to-treat improves after neoadjuvant gemcitabine-based chemoradiotherapy or chemotherapy (various regimens), as compared to immediate surgery followed by adjuvant chemotherapy. Radiotherapy appears to play an important role in mediating locoregional effects. Yet, since more effective chemotherapy regimens are currently available, in particular FOLFIRINOX and Gemcitabine/Nab-paclitaxel, these chemotherapy regimens should be investigated in future randomized trials combined with (stereotactic) radiotherapy to further improve outcomes of RPC and BRPC

A phase ib clinical trial of metformin and chloroquine in patients with IDH1-mutated solid tumors

Simple SummaryMutations in the isocitrate dehydrogenase 1 (IDH1) gene occur in high-grade chondrosarcoma, high-grade glioma and intrahepatic cholangiocarcinoma. Due to the lack of effective treatment options, these aggressive types of cancer have a dismal outcome. The metabolism of IDH1-mutated cancer cells is reprogrammed in order to produce the oncometabolite D-2-hydroxyglutarate (D-2HG). In this clinical trial, we used the oral antidiabetic drug metformin and the oral antimalarial drug chloroquine to disrupt the vulnerable metabolism of IDH1-mutated solid tumors. We found that the combination regimen of metformin and chloroquine is well tolerated, but the combination did not induce a clinical response in this patient population. Secondly, we confirmed the clinical usefulness of D/L-2HG ratios in serum as a biomarker and the ddPCR-facilitated detection of an IDH1 mutation in circulating DNA from peripheral blood.Background: Mutations in isocitrate dehydrogenase 1 (IDH1) occur in 60% of chondrosarcoma, 80% of WHO grade II-IV glioma and 20% of intrahepatic cholangiocarcinoma. These solid IDH1-mutated tumors produce the oncometabolite D-2-hydroxyglutarate (D-2HG) and are more vulnerable to disruption of their metabolism. Methods: Patients with IDH1-mutated chondrosarcoma, glioma and intrahepatic cholangiocarcinoma received oral combinational treatment with the antidiabetic drug metformin and the antimalarial drug chloroquine. The primary objective was to determine the occurrence of dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD). Radiological and biochemical tumor responses to metformin and chloroquine were investigated using CT/MRI scans and magnetic resonance spectroscopy (MRS) measurements of D-2HG levels in serum. Results: Seventeen patients received study treatment for a median duration of 43 days (range: 7-74 days). Of twelve evaluable patients, 10 patients discontinued study medication because of progressive disease and two patients due to toxicity. None of the patients experienced a DLT. The MTD was determined to be 1500 mg of metformin two times a day and 200 mg of chloroquine once a day. A serum D/L-2HG ratio of >= 4.5 predicted the presence of an IDH1 mutation with a sensitivity of 90% and a specificity of 100%. By utilization of digital droplet PCR on plasma samples, we were able to detect tumor-specific IDH1 hotspot mutations in circulating tumor DNA (ctDNA) in investigated patients. Conclusion: Treatment of advanced IDH1-mutated solid tumors with metformin and chloroquine was well tolerated but did not induce a clinical response in this phase Ib clinical trial.Molecular tumour pathology - and tumour geneticsMTG

Evaluation of LHP® (1% hydrogen peroxide) cream versus petrolatum and untreated controls in open wounds in healthy horses: a randomized, blinded control study

<p>Abstract</p> <p>Background</p> <p>Treatment and protection of wounds in horses can be challenging; protecting bandages may be difficult to apply on the proximal extremities and the body. Unprotected wounds carry an increased risk of bacterial contamination and subsequent infection which can lead to delayed wound healing. Topical treatment with antimicrobials is one possibility to prevent bacterial colonization or infection, but the frequent use of antimicrobials ultimately leads to development of bacterial resistance which is an increasing concern in both human and veterinary medicine.</p> <p>Methods</p> <p>Standardized wounds were created in 10 Standardbred mares. Three wounds were made in each horse. Two wounds were randomly treated with LHP^®or petrolatum and the third wound served as untreated control. All wounds were assessed daily until complete epithelization. Protocol data were recorded on day 2, 6, 11, 16, 21 and 28. Data included clinical scores for inflammation and healing, photoplanimetry for calculating wound areas and swab cytology to assess bacterial colonization and inflammation. Bacterial cultures were obtained on day 2, 6 and 16.</p> <p>Results</p> <p>Mean time to complete healing for LHP^®treated wounds was 32 days (95%CI = 26.9-37.7). Mean time to complete healing for petrolatum and untreated control wounds were 41.6 days (95%CI = 36.2-47.0) and 44.0 days (95%CI = 38.6-49.4) respectively. Wound healing occurred significantly faster in LHP^®wounds compared to both petrolatum (p = 0.0004) and untreated controls (p < 0.0001). There was no significant difference in time for healing between petrolatum and untreated controls. Total scores for bacteria and neutrophils were significantly (p < 0.0001) lower for LHP^®treated wounds compared to petrolatum from day 16 and onwards. <it>Staphylococcus aureus </it>and <it>Streptococcus zooepidemicus </it>were only found in cultures from petrolatum treated wounds and untreated controls.</p> <p>Conclusions</p> <p>Treatment with LHP^®reduced bacterial colonization and was associated with earlier complete wound healing. LHP^®cream appears to be safe and effective for topical wound treatment or wound protection.</p

ACE Inhibition and Endothelial Function: Main Findings of PERFECT, a Sub-Study of the EUROPA Trial

Background: ACE inhibition results in secondary prevention of coronary artery disease (CAD) through different mechanisms including improvement of endothelial dysfunction. The Perindopril-Function of the Endothelium in Coronary artery disease Trial (PERFECT) evaluated whether long-term administration of perindopril improves endothelial dysfunction. Methods: PERFECT is a 3-year double blind randomised placebo controlled trial to determine the effect of perindopril 8 mg once daily on brachial artery endothelial function in patients with stable CAD without clinical heart failure. Endothelial function in response to ischaemia was assessed using ultrasound. Primary endpoint was difference in flow-mediated vasodilatation (FMD) assessed at 36 months. Results: In 20 centers, 333 patients randomly received perindopril or matching placebo. Ischemia-induced FMD was 2.7% (SD 2.6). In the perindopril group FMD went from 2.6% at baseline to 3.3% at 36 months and in the placebo group from 2.8 to 3.0%. Change in FMD after 36 month treatment was 0.55% (95% confidence interval −0.36, 1.47; p = 0.23) higher in perindopril than in placebo group. The rate of change in FMD per 6 months was 0.14% (SE 0.05, p = 0.02) in perindopril and 0.02% (SE 0.05, p = 0.74) in placebo group (0.12% difference in rate of change p = 0.07). Conclusion: Perindopril resulted in a modest, albeit not statistically significant, improvement in FMD

Quantitative radiologic criteria for the diagnosis of lumbar spinal stenosis: a systematic literature review

Background: Beside symptoms and clinical signs radiological findings are crucial in the diagnosis of lumbar spinal stenosis (LSS). We investigate which quantitative radiological signs are described in the literature and which radilogical criteria are used to establish inclusion criteria in clincical studies evaluating different treatments in patients with lumbar spinal stenosis. Methods: A literature search was performed in Medline, Embase and the Cochrane library to identify papers reporting on radiological criteria to describe LSS and systematic reviews investigating the effects of different treatment modalities. Results: 25 studies reporting on radiological signs of LSS and four systematic reviews related to the evaluation of different treatments were found. Ten different parameters were identified to quantify lumbar spinal stenosis. Most often reported measures for central stenosis were antero-posterior diameter (< 10 mm) and cross-sectional area (< 70 mm2) of spinal canal. For lateral stenosis height and depth of the lateral recess, and for foraminal stenosis the foraminal diameter were typically used. Only four of 63 primary studies included in the systematic reviews reported on quantitative measures for defining inclusion criteria of patients in prognostic studies. Conclusions: There is a need for consensus on well-defined, unambiguous radiological criteria to define lumbar spinal stenosis in order to improve diagnostic accuracy and to formulate reliable inclusion criteria for clinical studies

Treatment and overall survival of four types of non-metastatic periampullary cancer:nationwide population-based cohort study

Background: Periampullary adenocarcinoma consists of pancreatic adenocarcinoma (PDAC), distal cholangiocarcinoma (DC), ampullary cancer (AC), and duodenal adenocarcinoma (DA). The aim of this study was to assess treatment modalities and overall survival by tumor origin. Methods: Patients diagnosed with non-metastatic periampullary cancer in 2012–2018 were identified from the Netherlands Cancer Registry. OS was studied with Kaplan–Meier analysis and multivariable Cox regression analyses, stratified by origin. Results: Among the 8758 patients included, 68% had PDAC, 13% DC, 12% AC, and 7% DA. Resection was performed in 35% of PDAC, 56% of DC, 70% of AC, and 59% of DA. Neoadjuvant and/or adjuvant therapy was administered in 22% of PDAC, 7% of DC, 7% of AC, and 12% of DA. Three-year OS was highest for AC (37%) and DA (34%), followed by DC (21%) and PDAC (11%). Adjuvant therapy was associated with improved OS among PDAC (HR = 0.62; 95% CI 0.55–0.69) and DC (HR = 0.69; 95% CI 0.48–0.98), but not AC (HR = 0.87; 95% CI 0.62–1.22) and DA (HR = 0.85; 95% CI 0.48–1.50). Conclusion: This retrospective study identified considerable differences in treatment modalities and OS between the four periampullary cancer origins in daily clinical practice. An improved OS after adjuvant chemotherapy could not be demonstrated in patients with AC and DA

Associations between the time of conception and the shape of the lactation curve in early lactation in Norwegian dairy cattle

<p>Abstract</p> <p>Background</p> <p>This study was carried out to determine if an association exists between the shape of the lactation curve before it is influenced by the event of conception and the time from calving to conception in Norwegian dairy cattle. Lactation curves of Norwegian Red cows during 5 to 42 days in milk (DIM) were compared between cows conceiving between 43 and 93 DIM and cows conceiving after 93 DIM.</p> <p>Methods</p> <p>Data from 23,049 cows, represented by one lactation each, with 219,538 monthly test days were extracted from the Norwegian Dairy Herd Recording System, which represents 97% of all Norwegian dairy cows. Besides veterinary treatments, these records also included information on daily milk yield at monthly test days. The data were stratified by parity groups (1, 2, and 3 and higher) and time to conception periods (43-93 DIM and >93 DIM). The sample was selected using the following selection criteria: conception later than 42 DIM, calving season July to September, no records of veterinary treatment and the level of energy fed as concentrates between 8.69 and 12.83 MJ. The shape of the lactation curves were parameterized using a modified Wilmink-model in a mixed model analysis. Differences in the parameters of the lactation curves with different conception times were evaluated using confidence intervals.</p> <p>Results</p> <p>Lactation curves characterized by a low intercept and a steep ascending slope and a steep descending slope were associated with early conception across all parities. The peak milk yield was not associated with time of conception.</p> <p>Conclusions</p> <p>A practical application of the study results is the use of the shape of the lactation curve in future herd management. Groups of cows with impaired reproductive performance may be identified due to an unfavorable shape of the lactation curve. Monitoring lactation curves and adjusting the feeding strategy to adjust yield therefore may be useful for the improvement of reproductive performance at herd level.</p