Voriconazole-Induced Cholestatic Hepatotoxicity in an Immune Competent Patient.

Voriconazole is a frequently prescribed anti-fungal medication used in particular for invasive aspergillosis. Voriconazole-induced hepatotoxicity is a relatively rare but serious clinicopathologic entity. We report a patient presenting with impaired liver function test results pointing towards the cholestatic picture. The patient had initial blood tests to confirm cholestasis, followed by imaging modalities that did not show any obstruction along the common bile duct and/or pancreatic pathway. The patient's voriconazole dose reduction was advised, resulting in lower levels of abnormal liver function tests.

Mesenteric ischaemia following posterior myocardial infarction.

An 84-year-old man was admitted with urinary tract infection and chest discomfort. He initially responded to conservative acute coronary syndrome management and antibiotics.On day 6 of admission, he developed acute severe abdominal pain; 12-lead electrocardiography showed widespread ST-segment depression in the anterior chest leads with ST-elevation in the posterior leads (V7-9) suggestive of an acute posterior myocardial infarction. Arterial blood gases showed severe metabolic acidosis with a lactate of 11 mmol/L.An urgent computed tomography angiography suggested acute small bowel ischaemia. The case was discussed with the on-call surgical team, who advised that, due to severe frailty, he was not fit for surgical intervention and should be managed conservatively. He was managed with intravenous heparin infusion and supportive measures, but sadly continued to deteriorate and was palliated. He died shortly afterwards.

Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern.

BACKGROUND: The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features. METHODS: Arab patients from the Arab Gulf region and a population of age- and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed. The mutation rates of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC were recorded, along with clinicopathological features. Other somatic mutation and their rates were also identified. Fisher's exact test was used to determine the association between mutation status and clinical features. RESULTS: A total of 198 cases were identified; 99 Arab patients and 99 Western patients. Fifty-two point seven percent of Arab patients had stage IV disease at initial presentation, 74.2% had left-sided tumors. Eighty-nine point two percent had tubular adenocarcinoma and 10.8% had mucinous adenocarcinoma. The prevalence rates of KRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7 mutations in Arab population were 44.4%, 4%, 4%, 13.1%, 52.5%, 27.3%, 2% and 3% respectively. Compared to 48.4%, 4%, 4%, 12.1%, 47.5%, 24.2%, 11.1% and 0% respectively in matched Western population. Associations between these mutations and patient clinicopathological features were not statistically significant. CONCLUSIONS: This is the first study to report comprehensive hotspot mutations using NGS in Arab patients with CRC. The frequency of KRAS, NRAS, BRAF, TP53, APC and PIK3CA mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of FBXW7 mutation.