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Fulltext Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk

Yuan F, Hung RJ, Walsh N, Zhang H, Platz EA, Wheeler W, et al.

Cancer Res, 2020 Sep 15;80(18):4004-4013.
PMID: 32641412 DOI: 10.1158/0008-5472.CAN-20-0447

Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10-6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. SIGNIFICANCE: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.

Matched MeSH terms: Pancreatitis, Chronic/genetics
Fulltext Knowledge, Perception, and Antibiotic Prescribing Practice in the Intensive Care Unit: Findings from the Malaysian Public Setting

Rozali MA, Abd Rahman NS, Sulaiman H, Abd Rahman AN, Atiya N, Wan Mat WR, et al.

J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S804-S809.
PMID: 33828380 DOI: 10.4103/jpbs.JPBS_266_19

Introduction: Approach to managing infection in the intensive care unit (ICU) often varies between institutions and not many readily adapt to available local guidelines despite it was constructed to suite local clinical scenario. Malaysia already has two published guidelines on managing infection in the ICU but data on its compliance are largely unknown.
Objectives: A cross-sectional survey was carried out and sent to a total of 868 specialists working primarily in the ICU. The aim of this study was to explore knowledge, perception, and the antibiotic prescribing practice among specialists and advanced trainees in Malaysian ICU.
Materials and Methods: A cross-sectional survey was used, consisted of three sections: knowledge, perception, and antibiotic prescribing practice in ICU. Three case vignettes on hospital-acquired pneumonia (HAP), infected necrotizing pancreatitis (INP), and catheter-related bloodstream infection (CRBSI) were used to explore antibiotic prescribing practice.
Results: A total of 868 eligible subjects were approached with 104 responded to the survey. Three hundred eighty-nine antibiotics were chosen from seven different classes in the case vignettes. All respondents acknowledged the importance of pharmacokinetic/pharmacodynamic (PK/PD) in antibiotic optimization and majority (97.2%) perceived that current dosing is inadequate to achieve optimal PK/PD target in ICU patients. Majority (85.6%) believed that antibiotic dose should be streamlined to the organisms' minimum inhibitory concentration (MIC). In terms of knowledge, only 64.4% provided the correct correlations between antibiotics and their respective PK/PD targets. Compliance rates in terms of antibiotic choices were at 79.8%, 77.8%, and 27.9% for HAI, INP, and CRBSI, respectively.
Conclusion: Malaysian physicians are receptive to use PK/PD approach to optimize antibiotic dosing in ICU patients. Nonetheless, there are still gaps in the knowledge of antibiotic PK/PD as well as its application in the critically ill, especially for β-lactams.

Matched MeSH terms: Pancreatitis
Biliary ascariasis: a wandering worm

Lim, C.B., Munirah, A., Alias, M., Nandy, A.K., Thamby Dorai, C.R.

Malaysian Journal of Paediatrics and Child Health, 2000;12(1):68-71.
MyJurnal

Ascaris lumbricoides infection usually results in mild gastrointestinal symptoms. However, heavy worm load infections can cause major complications. In one-third of the latter cases, the worms enter the bile duct causing cholangitis, biliary colic and acute pancreatitis. We describe an eleven-year-old Indian boy who presented with high grade fever, vomiting of worms, jaundice and right hypochondria! pain. Examination revealed an ill, malnourished and jaundiced child. His abdomen was tender with positive Murphy's sign and hepatomegaly. Urgent ultrasound showed hepatomegaly with dilated intrahepatic and common bile ducts (CBD). There were tubular echogenic filling defects with central sonolucency along the long axis of the CBD. He was fasted, started on intravenous fluids and broad spectrum antibiotics. As there was no improvement after 24 hours, endoscopic retrograde cholangio-pancreaticography (ERCP) was performed: it showed worms in the CBD. A stent was inserted to decompress the bile ducts and to ensure biliary drainage. The patient improved, the fever settled, jaundice resolved, serum amylase and transaminase levels normalised. It was planned to remove the stent at a later date.

Matched MeSH terms: Pancreatitis
Fulltext Sodium valproate induced necrotising pancreatitis: A case report

Ali MF, Loh KY

Malays Fam Physician, 2013;8(3):28-30.
PMID: 25893054 MyJurnal

Sodium valproate is one of the most common first-line antiepileptics prescribed for primary and secondary generalised seizures. However, serious complications associated with sodium valproate, such as acute pancreatitis, need to be considered when choosing this medication for treating epilepsy in certain populations such as children and persons with intellectual disability. We report a case of a 21-year-old man with intellectual disability who presented to the emergency department with an acute abdomen, vomiting and diarrhoea. He had to undergo an emergency exploratory laparotomy during which acute necrotising pancreatitis was diagnosed intra-operatively. We believe that the recent increase in sodium valproate dosage for his epilepsy was the cause of the pancreatitis. Carers of such persons should be adequately informed regarding possible life-threatening complications of medications prescribed to avoid delay in diagnosis and unwanted incidents.

Matched MeSH terms: Pancreatitis, Acute Necrotizing
Fulltext Occipital Falcine Anaplastic Hemangiopericytoma Mimicking Meningioma

Kanesen D, Kandasamy R, Idris Z

J Neurosci Rural Pract, 2016 Dec;7(Suppl 1):S95-S98.
PMID: 28163517 DOI: 10.4103/0976-3147.196463

The rarity of hemangiopericytoma (HPC) and its controversial histological classification result in its frequent misdiagnosis and thus make the treatment quite challenging. It is often difficult to distinguish these tumors from meningiomas based on clinical features and radiological findings. This is a case report of a man, diagnosed clinically and radiologically as meningioma, which turned out to be anaplastic HPC on histological examination. A 30-year-old man presented with 3 months of progressively worsening of headache and blurring of vision. Clinical examination revealed the right homonymous hemianopia with reduced visual acuity and papilledema bilaterally. Magnetic resonance imaging revealed a multilobulated and heterogenous extraaxial lesion attached to the occipital falx. It measured 9.0 cm (AP) × 5.5 cm (W) × 5.8 cm (CC) and expands bilaterally with major bulk on the left. An occipital craniotomy followed by a subtotal tumor excision was only achieved due to profuse bleeding intraoperatively. Histopathology confirmed an anaplastic HPC (WHO Grade 3). The importance of differentiation between HPCs and meningiomas cannot be overemphasized. A preoperative correct diagnosis is difficult, but it is important that it should be made. Multilobulated (mushroom appearance), prominent internal signal voids, relatively narrow dural attachment, and lytic destruction without calcifications are useful findings to distinguish HPCs from meningiomas.

Matched MeSH terms: Pancreatitis, Chronic