Objective: Having a heart healthy life is one of the most rewarding gifts that you can own yourself in the modern lifestyle practices. Cardiac rehabilitation (CR) is the next step to recover and reverse the limitations experienced by patients who have undergone all the adverse pathophysiological and psychological consequences of cardiac events. Design: This is a review article. The need for cardiac rehabilitation: CR describes all the methods and measures used to prevent recurrent cardiac attaches and to return people with heart diseases to an active and a satisfying lifestyle. CR services should be offered by all health professionals who are in direct contact with the patient, like cardiac specialist, general practitioner, and other health care providers. The success rate of the CR program improves dramatically when it comes in parallel with limiting modifiable risk factors of cardiovascular diseases. The CR programs not only manage episodes of cardiac events, but also it is a comprehensive tool for preventing future heart problems and improving the patients' life standard. Goals of Cardiac rehabilitation (CR): CR program has been evolved with a wide range of indications that aims to regain autonomy and maximize the physical, psychological and social activities. This makes people with cardiac diseases more confident and inspires behaviors that may minimize risk of further cardiac events. The vision to improve CR in Saudi Arabia: This article will focus on the methods and parameters that will lead to an improvement in the CR services in the Kingdom of Saudi Arabia.

Background:Regorafenib is a multi-kinase inhibitor approved for treatment of refractory advanced colorectal cancer. It was found in the clinical trials to have a modest benefit and significant toxicity. Our aim was to assess the outcome in our local clinic practice.Patients and methods:Records of patients with confirmed colorectal cancer treated with regorafenib were reviewed. Clinical, pathological, and molecular data were collected. Efficacy and factors of possible prognostic significance were analyzed.Results:A total of 78 patients with metastatic colorectal cancer were treated with regorafenib from February 2014 to February 2016 in 4 different institutions (median age: 50.5 years; male: 40 [51.3%]; KRAS mutant: 41 [52%]; right colonic primary: 18 [23%]). A total of 52 patients (66.7%) had Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1, whereas in 25 patients (32.1%) it was >1. In total, 58 patients (74%) had dose reduction. No patient achieved objective response, 15 patients (19%) achieved stable disease, and 56 patients (72%) had progressive disease. With a median follow-up of 6.5 months, the median progression-free survival was 2.8 months (95% confidence interval [CI], 2.5-3.3) and overall survival was 8.0 months (95% CI, 6.2-9.7). Only performance status of ⩽1 had a statistically significant impact on progression-free survival and overall survival in both univariate and multivariate analyses.Conclusions:Regorafenib in our clinical practice has equal efficacy to reported data from pivotal registration trials. Our data suggest that performance status is the most important prognostic factor in patients treated with regorafenib, suggesting a careful selection of patients.

The steady-state kinetics of amitriptyline (AMI), fluoxetine (FLU), and their active metabolites nortriptyline (NTRIP) and norfluoxetine (NFLU) were studied in 15 patients treated once daily for long durations with 50 mg of AMI and 20 mg of FLU. These compounds were analyzed simultaneously in plasma by liquid chromatography. The means and (SEM) of the steady-state concentrations (Css) of AMI, NTRIP, FLU, and NFLU were 80.6 (14.2), 52.6 (10.3), 85.3 (16.1), and 90 (13.6) ng/mL, respectively, and the apparent oral clearances (CLor) of AMI and FLU were 42.4 (8.6) and 14.9 (2.5) L/hr, respectively. The metabolite/drug steady-state concentration ratio (Css(m)/Css) for NTRIP/AMI was 0.75 (0.14) and for NFLU/FLU was 1.27 (0.17). There was a significant correlation (P < 0.05) between Css of FLU and that of AMI or NTRIP. The Css and Css(m)/Css values obtained for AMI were higher (P < 0.056 and P < 0.0034, respectively) than those we observed in 10 patients treated solely with the same dose of AMI. The twofold increase in Css of AMI and ninefold increase in Css of NTRIP seem to be the result of inhibition of the metabolism of these compounds by FLU, particularly the ring hydroxylation. Norfluoxetine may have a small inhibitory influence on the metabolism of NTRIP but lacks this effect on the metabolism of AMI.

Background Locally advanced breast cancer (LABC), the most aggressive form of the disease, is a serious threat for women's health worldwide. The AU-rich RNA-binding factor 1 (AUF1) promotes the formation of chemo-resistant breast cancer stem cells. Thereby, we investigated the power of AUF1 expression, in both cancer cells and their stromal fibroblasts, as predictive biomarker for LABC patients’ clinical outcome following neoadjuvant treatment. Methods We have used immunohistochemistry to assess the level of AUF1 on formalin-fixed paraffin-embedded tissues. Immunoblotting was utilized to show the effect of AUF1 ectopic expression in breast stromal fibroblasts on the expression of various genes both in vitro and in orthotopic tumor xenografts. Cytotoxicity was evaluated using the WST1 assay, while a label-free real-time setting using the xCELLigence RTCA technology was utilized to assess the proliferative, migratory and invasive abilities of cells. Results We have shown that high AUF1 immunostaining (≥ 10%) in both cancer cells and their adjacent cancer-associated fibroblasts (CAFs) was significantly associated with higher tumor grade. Kaplan–Meier univariate analysis revealed a strong correlation between high AUF1 level in CAFs and poor patient’s survival. This correlation was highly significant in patients with triple negative breast cancer, who showed poor disease-free survival (DFS) and overall survival (OS). High expression of AUF1 in CAFs was also associated with poor OS of ER+/Her2− patients. Similarly, AUF1-positive malignant cells tended to be associated with shorter DFS and OS of ER+/Her2+ patients. Interestingly, neoadjuvant therapy downregulated AUF1 to a level lower than 10% in malignant cells in a significant number of patients, which improved both DFS and OS. In addition, ectopic expression of AUF1 in breast fibroblasts activated these cells and enhanced their capacity to promote, in an IL-6-dependent manner, the epithelial-to-mesenchymal transition and stemness processes. Furthermore, these AUF1-expressing cells enhanced the chemoresistance of breast cancer cells and their growth in orthotopic tumor xenografts. Conclusions The present findings show that the CAF-activating factor AUF1 has prognostic/predictive value for breast cancer patients and could represent a great therapeutic target in order to improve the precision of cancer treatment.

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Objectives: Ovarian granulosa cell tumour is rare. This study aims to report the clinical characteristics and long-term outcomes of adult-type ovarian granulosa cell tumour (AOGCT) at King Faisal Specialist Hospital and Research Centre (KFSH&RC) and to determine the prognostic factors affecting relapse and survival.Methods: We retrospectively reviewed patients with AOGCT, from 1988 to 2014, who were treated at our institution. Baseline characteristics, pathological findings, and outcomes were analysed and reported.Results: Sixty-one patients with AOGCT were identified with a median age of 49 years. Median follow-up was 5.0 years (range 2.1-8.2 years). 74% of patients were FIGO (International Federation of Gynecology and Obstetrics) stage I, whereas 7% were stage II, 5% were stage III, and unknown in 14% of the cases. The most common presenting symptoms included abdominal pain (43%) and vaginal bleeding (43%). The majority of patients (38 patients, 62%) were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Five (8%) patients received adjuvant chemotherapy. Sixteen patients (26%) relapsed with a median time to relapse of 5.5 years (0.7-8.1 years). Half of the recurrences (eight patients, 50%) occurred after five years of diagnosis. Five-year overall survival and disease-free survival (DFS) were 93% and 84%, respectively. Factors associated with a high risk of recurrence were the presence of ascites (p=0.000) and elevated preoperative CA 125 level (p=0.048). The overall survival was significantly influenced by the menopausal status (premenopausal 100% vs. postmenopausal 84%; p=0.02), preoperative CA 125 (normal 100% vs. elevated 64%; p=0.005), ascites (present 33% vs. absent 100%; p=0.000), and age (<55 years 100% vs. ≥ 55 years 77%; p= 0.002). Conclusion:This study confirms a good outcome for patients with AOGCT. They require long-term follow-up as late recurrences can occur many years post definitive therapy. The presence of ascites and elevated preoperative CA 125 levels were associated with a higher risk of recurrence and poor prognosis. Outcomes appear unaffected by fertility-sparing surgery or adjuvant chemotherapy.

Background Tyrosine kinase inhibitors remain a cornerstone in managing metastatic clear cell renal cell carcinoma (RCC). The 4 weeks on/2 weeks off intermittent sunitinib schedule could result in rebound angiogenesis and tumor progression in the 2-week rest period. We propose using bevacizumab during this period for continuous antiangiogenic effects. Method This was a phase I/II study of patients with advanced clear cell RCC. Sunitinib was given 50 mg daily on a 4-week on/2-week off schedule. Bevacizumab was given on day 29 of each sunitinib cycle. The bevacizumab starting dose was 5 mg/kg, and the dose was escalated to 10 mg if there was no dose-limiting toxicity. The primary endpoints were response rate and progression-free survival (PFS). Results Twenty-five patients were recruited. The study was closed prematurely because of poor accrual. No dose-limiting toxicity was observed with 5 mg bevacizumab. One patient achieved a complete response, and 12 achieved a partial response (52% response rate). At a median follow-up of 42.2 months (95%, confidence interval (CI) 32.9 to 51.4), the median PFS duration was 16.5 months (95% CI 4.1-28.8), and the median overall survival time was 33.3 months (95% CI 19.4-47.3). Twenty-two patients (88%) had at least one grade 3 or 4 toxicity; the most common were thrombocytopenia (32%), lymphopenia (32%), hypertension (28%), and fatigue (24%). Conclusion Continuous angiogenesis blockade by adding bevacizumab to the sunitinib on/off regimen for advanced RCC yields significant antitumor activity with manageable increased toxicity.

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