Safety and efficacy of favipiravir versus hydroxychloroquine in management of COVID-19: A randomised controlled trial.

Favipiravir is considered a potential treatment for COVID-19 due its efficacy against different viral infections. We aimed to explore the safety and efficacy of favipiravir in treatment of COVID-19 mild and moderate cases. It was randomized-controlled open-label interventional phase 3 clinical trial [NCT04349241]. 100 patients were recruited from 18th April till 18th May. 50 patients received favipiravir 3200 mg at day 1 followed by 600 mg twice (day 2-day 10). 50 patients received hydroxychloroquine 800 mg at day 1 followed by 200 mg twice (day 2-10) and oral oseltamivir 75 mg/12 h/day for 10 days. Patients were enrolled from Ain Shams University Hospital and Assiut University Hospital. Both arms were comparable as regards demographic characteristics and comorbidities. The average onset of SARS-CoV-2 PCR negativity was 8.1 and 8.3 days in HCQ-arm and favipiravir-arm respectively. 55.1% of those on HCQ-arm turned PCR negative at/or before 7th day from diagnosis compared to 48% in favipiravir-arm (p = 0.7). 4 patients in FVP arm developed transient transaminitis on the other hand heartburn and nausea were reported in about 20 patients in HCQ-arm. Only one patient in HCQ-arm died after developing acute myocarditis resulted in acute heart failure. Favipiravir is a safe effective alternative for hydroxychloroquine in mild or moderate COVID-19 infected patients.

Outcome of cervix uteri cancer patients: Clinical treatment results and toxicity profile in a retrospective study from Saudi Arabia.

AIM: This study evaluated the survival outcome, pattern of failure and prognostic factors in cervix uteri cancer patients. METHODS: We reviewed the data of 60 patients with stages IB-IVA cancer who were treated between January 2004 and December 2010. RESULTS: Most patients (n = 50; 83%) had squamous cell carcinoma. Stage IIB was the most common presentation (n = 41; 68%). Forty-seven patients (78%) received Cisplatin concurrent with radiotherapy (CRT). The 2- and 4-year overall survival (OS) was 82% and 79%, respectively. Prolongation of the overall treatment time (OAT) for greater than 56 days, advanced stage and pretreatment hemoglobin (Hb) levels (<10 g/dL) negatively predicted OS (P = 0.039, P = 0.044 and P = 0.008, respectively). The 2- and 4-year disease-free survival (DFS) rates were 80% and 69%, respectively. Vaginal infiltration and brachytherapy (orthogonal versus CT-based planning) were significant factors for the prediction of relapse (P = 0.048 and P = 0.049, respectively). The 2- and 4-year loco-regional control (LRC) rates were 78% and 70%, respectively, and the distant metastasis-free survival (DMFS) rates were 82% and 79%, respectively. Vaginal infiltration was the only negative predictive factor for LRC (P = 0.045), and pathological tumor grade was the only factor indicative of distant metastases (P = 0.037). Grade 3 or 4 late rectal reactions were reported in two patients (3%), and no patients developed grade 3 or 4 urinary reactions. CONCLUSION: The treatment results in our cervix uteri cancer patients and the prognostic factors are comparable to those of previous reports. Orthogonal brachytherapy planning and vaginal infiltration negatively predicted relapse.

Lymph node ratio may predict relapse free survival and overall survival in patients with stage II & III colorectal carcinoma.

BACKGROUND/AIMS: Lymph node ratio (LNR) defined as the number of lymph nodes (LNs) involved with metastases divided by number of LNs examined, has been shown to be an independent prognostic factor in breast, stomach and various other solid tumors. Its significance as a prognostic determinant in colorectal cancer (CRC) is still under investigation. This study investigated the prognostic value of LNR in patients with resected CRC. METHODOLOGY: We retrospectively ex- amined 145 patients with stage II & III CRC diagnosed and treated at a single institution during 9 years pe- riod. Patients were grouped according to LNR in three groups. Group 1; LNR < 0.05, Group 2; LNR = 0.05-0.19 & Group 3 > 0.19. Chi square, life table analysis and multivariate Cox regression were used for statistical analysis. RESULTS: On multivariate analysis, number of involved LNs (NILN) (HR = 1.15, 95% CI 1.055-1.245; P = 0.001) and pathological T stage (P = 0.002) were statistically significant predictors of relapse free survival (RFS). LNR as a continuous variable (but not as a categorical variable) was statistically significant predictor of RFS (P = 0.02). LNR was also a statistically significant predictor of overall survival (OS) (P = 0.02). CONCLUSION: LNR may predict RFS and OS in patients with resected stage II & III CRC. Studies with larger cohorts and longer follow up are needed to further examine and validate theprognostic value of LNR.

Phase II study on the use of intraoperative radiotherapy in early breast cancer.

OBJECTIVE: To report our early experience using the Intrabeam radiotherapy delivery system for intraoperative radiotherapy (IORT) in early breast cancer. METHODS: This is a prospective phase 2 study carried out at the Department of Surgery and Radiology, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia from December 2010 to November 2012. Females eligible for breast-conserving surgery with biopsy-proven invasive duct carcinoma, and with a mass of 3 cm, with lymphovascular invasion, multifocal lesion, extensive intraductal carcinoma, and positive nodes. Early and late toxicity were recorded using the Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: Forty-five patients were included with a median age of 54 (range: 27-79 years). Thirty-six cases (80%) had tumor <3 cm in diameter, and 36 (67%) have pathologically negative axillary lymph node metastases. None of the patients developed delayed wound healing, postoperative infection requiring intravenous antibiotic, or breast seroma requiring aspiration. Sixteen (36%) received EBRT after IORT. Twelve patients developed radiologically proved fat necrosis. CONCLUSION: The IORT for early stage breast cancer patients using the Intrabeam delivery system was easily implemented in our center with an acceptable toxicity profile and cosmetic outcome.

Prognostic value of lymph node ratio in poor prognosis node-positive breast cancer patients in Saudi Arabia.

AIM: Women in Saudi Arabia develop breast cancer at a young age with high prevalence of poor prognostic features. Because of such features, it is necessary to examine prognostic factors in this population. One such factor is the prognostic role of lymph node ratio (LNR). METHODS: We performed retrospective analyses of patients with invasive non-metastatic breast cancer who underwent axillary lymph node dissection and had one or more positive axillary lymph nodes. RESULTS: Two hundred and seventeen patients were considered eligible for the analysis. The median age was 46 years. At a median follow-up of 39.8 months, the median disease-free survival (DFS) was 67.3 months (95% CI, 50.4 to 84.3 months). Neither the classification of patients based on positive lymph node (pN) staging system, nor the absolute number of pN prognosticated DFS. Conversely, age 0.20 to 0.65) LNR categories were the only variables that were independently associated with adverse DFS. Using these variables in a prognostic model allowed the classification of patients into three distinctive risk strata. The overall survival (OS) in this series was 92.5 months (95% CI, 92.1-92.6). Only ER negative tumor adversely influenced OS. CONCLUSION: Analysis of survival outcome of mostly young patients with early breast cancer identified adverse prognostic variables affecting DFS. If the utility of the derived model including LNR is proven in a larger patient population, it may replace the use of absolute number of positive axillary lymph nodes.

Basal vs. luminal A breast cancer subtypes: a matched case-control study using estrogen receptor, progesterone receptor, and HER-2 as surrogate markers.

Breast cancer is a heterogeneous disease that encompasses several distinct entities with different biological characteristics and clinical behavior. Basal subtype is considered as a prognostically unfavorable subset. The purpose of this study is to compare the clinico-pathological characteristics and outcome of basal vs. luminal A subtype, as approximated by ER, PR, and HER-2. Sixty-four patients with basal breast cancer were matched for age, stage, and year of diagnosis with 64 patients having luminal A disease. Basal tumors were immunohistochemically defined by a lack of expression of estrogen receptor (ER), progesterone receptor (PR), and HER-2, while luminal A cancers were ER+ or PR+, and HER-2-. As compared with luminal A, basal subtype patients had significantly larger primary tumor size, higher percentage of grade III tumor, more tumor that showed lymphovascular invasion, less presence of non-invasive disease, and higher proportion of extranodal extension. There was no statistically significant difference in metastatic sites, pathology type, or in the axillary lymph nodal status. A few patients received neoadjuvant chemotherapy--13 and 9 patients in basal and luminal A groups, respectively). The complete pathological response was 20% and 14%, respectively (not significant). At a median follow-up of approximately 2 years, there was no statistically significant difference in the overall survival rate between basal and luminal A patients. Analysis of disease-free survival (DFS) for stage I-III (53 patients in each group) showed that the median DFS for basal patients was 41.4 months (95% CI, 26.5-55.3 months), whereas the DFS for the luminal A patients was not reached (P = 0.014). After adjusting for several significant prognostics variables identified in a univariate analysis, a multivariate conditional logistic regression analysis identified the negative effect of lymphovascular invasion and the favorable influence of the use of neoadjuvant and/or adjuvant chemotherapy. This matched case-control study confirmed the poor clinical and pathological characteristics of patients with basal subtype and their unfavorable outcome compared with luminal A disease. Management of basal tumors remains a challenging task, and new therapeutic strategies are warranted.

A prospective study of antituberculous drug-induced hepatotoxicity in an area endemic for liver diseases.

PURPOSE: Identification of risk factors associated with antituberculosis drug-induced hepatotoxicity (anti-TB-DIH) is important, especially in endemic area for TB and liver disease. This study assessed the incidence and risk factors of anti-TB-DIH in upper Egyptian patients treated for active pulmonary and extra-pulmonary TB. METHODS: A total of 100 consecutive TB patients were prospectively followed up both clinically and biochemically before and during their course of anti-TB therapy with daily doses of isoniazid, rifampin, ethambutol, and pyrazinamide, or streptomycin. RESULTS: Anti-TB-DIH developed in 15 (15%) patients within 15-60 days (median: 30 days) from the onset of therapy. Liver function normalized in 10 (60%) patients within 2 weeks from cessation of therapy. No recurrence of DIH was observed after reintroduction of therapy. Only 1 patient died from fulminant hepatic failure despite discontinuation of all anti-TB drugs. By univariate analysis, patients with anti-TB-DIH had more pre-existing liver disease (P = 0.024; OR: 3.60; 95% CI: 1.16-11.18), lower body mass index (BMI; P = 0.037; OR: 3.73; 95% CI: 1.04-10.56), lower serum albumin (P = 0.035; OR: 3.31; 95% CI: 1.04-10.56), and more extensive disease (P = 0.033; OR: 3.50; 95% CI: 1.11-11). Age, gender, raised baseline transaminases level, inclusion of pyrazinamide, and inactive hepatitis B or C carrier state were not significant risk factors of DIH. Using multivariate regression analysis, only pre-existing liver disease and lower BMI of 20 kg/m(2) or less were independent predictors of DIH (P = 0.024 and P = 0.047, respectively). CONCLUSION: Anti-TB-DIH is not uncommon, needs early recognition and treatment, and is more in patients with pre-existing liver disease and low BMI.