Berberine ameliorates the progression of primary sclerosing cholangitis by activating farnesoid X receptor.

Primary sclerosing cholangitis (PSC) is a rare cholestatic disease characterized by biliary infiltration, hepatic fibrosis and bile duct destruction. To date, treatment options for PSC are very limited. Therefore, the current study is aimed to investigate the therapeutic potential of berberine (BBR) against PSC. The disease was induced by feeding the mice with 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC) for four weeks. The serum biochemistry and liver histology were analyzed. Furthermore, the expression of farnesoid X receptor (FXR) was also evaluated by real-time PCR. The results indicated that berberine prevents the progression of PSC by modulating the expression of FXR which ultimately regulates other genes (including Cyp7A1 and BSEP) thus maintaining bile acids homeostasis. Furthermore, the docking analysis showed that berberine interacts with the binding pocket of FXR to activate the protein thus acting as an FXR agonist. In conclusion, data indicate that berberine protects the liver from PSC-related injury. This effect might be due to the modulation of FXR activity.

COVID-19 Vaccinations: Summary Guidance for Cancer Patients in 28 Languages: Breaking Barriers to Cancer Patient Information.

BACKGROUND: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations. METHODS: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries. RESULTS: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population. CONCLUSION: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level.

Metastatic melanoma: a regional review and future directions.

AIMS AND BACKGROUND: . The incidence of malignant melanoma has risen steadily over recent decades. NCI data from 2005-2007 have suggested that 1.93% of individuals born today in the US will develop melanoma at some stage. Approximately 15% of patients with MM either present with metastatic disease or develop metastases during the course of their illness. Unfortunately, metastatic MM remains a challenge with limited treatment options, and median overall survival is 6-9 months. METHODS: We reviewed our data for the treatment of metastatic MM over a period of four years. Data from all patients with metastatic MM treated with systemic therapy without clinical trials from 2006 to 2009 were reviewed. Response rate was determined as per RECIST criteria. RESULTS: Sixty four patients were treated with one or more lines of cytotoxic therapy. Median age was 62 years (range, 23-82) with 53% males. Primary site of the disease was the skin in 75%, mucosal in 12.5%, ocular in 9.4% and nodal with an occult primary in 3.1%. Visceral metastases were present in 75% of patients at the start of treatment, including pulmonary (39.6%) and hepatic (34.4%). All patients were screened for brain metastases, which were present in 26.5% of patients. ECOG performance status was 0 in 7.8%, 1 in 68.7%, 2 in 9.4% and undocumented in the remaining 14%. Patients without brain metastases received single agent DTIC as first line; those with brain metastases received temozolomide. Response rate was 7% for DTIC and 28% for temozolomide, with median progression-free survival of 2.4 and 3.2 months, respectively. Seven patients who received DTIC are alive on follow-up, 2 have ongoing stable disease post-DTIC at 41 months and 18 months. Second line therapy with vinblastine was given to 21 patients (32%), with a response rate of 9.5% and median progression-free survival of 3.4 months. Median overall survival from initiation of therapy was 7.7 months for DTIC and 3.6 months for patients with brain metastases receiving temozolomide. A performance status of 2 was associated with shorter median overall survival (2.0 months). CONCLUSIONS: . Our results are comparable to published data. Malignant melanoma is a disease with rising incidence and limited treatment options. These patients are best treated in the context of clinical trials as new targeted therapies are promising as future strategies.

A prospective study of cefepime versus ticarcilline/clavulanate as empirical treatment of febrile neutropenia in lymphoma patients.

OBJECTIVE: To check the effectiveness of ticarcillin clavulanate versus cefepime as monotherapy in febrile neutropenia in lymphoma patients and also to check tolerability profile of both drugs. METHODS: We randomly assigned 107 neutropenic patients to receive either cefepime or ticarcillin/clavulanate. The clinical efficacy and tolerability profile of both drugs were compared using either cefepime or ticarcillin clavulanate (TC) as an empirical treatment for management of febrile neutropenia in lymphoma patients only with same characteristics at time of presentation. RESULTS: A significant difference in efficacy of the two treatment arms was noted. A successful outcome was reported with 28 (51%) out of 55 in cefepime arm compared to 16 (42%) out of 52 patients in ticarcillin/clavulanate group (p = 0.35; 95% Confidence). The distribution of time for defervesence was estimated for each treatment group and a trend to a shorter time for defervesence was found in the CEFEPIME group (48.4 hour for cefepime, 58.28 hour for TC group; p = 0.018). For microbiologically documented infections, the successful eradication rate was 49% (6 of 14 patients) for TC group as compared to 83% (10 of 12 patients) for cefepime group. This difference was statistically significant for microbiologically documented infections. Twenty seven (52%) patients of TC group and 19 (35%) of cefepime group required modifications of antibiotic regimen. The most frequent modifications consisted of the addition of either an amino glycoside (amikacin) or glycopeptides (vancomycin). CONCLUSION: CEFEPIME regimen was more effective than TC regimen, with a consistent trend toward a better outcome associated with cefepime compared to Ticarcillin/clavulanate.

Five years experience of sarcoidosis at a tertiary care centre in Pakistan.

OBJECTIVE: To review the medical records of patients diagnosed with sarcoidosis for sociodemographic characteristics, clinical presentation, mode of diagnosis, and stage of disease at a tertiary care centre of Pakistan. METHOD: The medical records of 47 patients consecutively diagnosed with sarcoidosis from 2003 to 2008 were reviewed retrospectively. The sociodemographic characteristics, clinical presentation, mode of diagnosis, organs involved, stage of disease and follow up were reviewed. RESULTS: Out of 47 patients, 26 (55%) were female and 21 male. Cough and shortness of breath were the main presenting symptoms. Mode of diagnosis was gallium scan in 27 patients, biopsy in 16 patients and High Resolution CT scan in 3 patients. Asymptomatic patients at presentation did not require any treatment and did well on follow up. Eighteen patients required steroid therapy which was slowly tapered off. Two patients required azathioprin in addition to steroids. CONCLUSION: Sarcoidosis is a diagnostic challenge in countries where tuberculosis is endemic, however physicians still need to keep sarcoidosis in the differential diagnosis due to clinical, histological and radiological similarities between the two conditions

Metastasis of carcinosarcoma of oesophagus to gastrostomy site.

Patients with head and neck cancers need a percutaneous endoscopic gastrosotomy (PEG) before start of treatment to ensure adequate nutrition because worsening dysphagia during chemo radiation [Nicholson FB, Korman MG, Richardson MA. Percutaneous endoscopic gastrostomy: a review of indications, complications and outcome. J. Gastroenterol Hepatol 2000; 15: 21-5; Beer KT, Krause KB, Zuercher T, Stanga Z. Early percutaneous endoscopic gastrostomy insertion maintains nutritional state in patients with aerodigestive tract cancer. Nutr Cancer 2005; 52: 29-34.]. However implantation of original tumor to the gastrostomy exit site is rare but serious complication of this procedure and here we report a case of PEG site metastasis along with relevant review of literature.