Late toxicity within a Phase III clinical trial of IG-IMRT in cervix cancer (PARCER): Reanalysis with time weighted adverse event reporting (MOSES).

BACKGROUND AND PURPOSE: This post-hoc analysis was performed to report the impact of Image guided intensity modulated radiotherapy (IG-IMRT) and three-dimensional conformal radiotherapy (3D-CRT) across organ system and grades of toxicity within PARCER trial (NCT01279135). Primary endpoint of PARCER focused on grade ≥ 2 late gastrointestinal (GI) toxicity using Common Terminology Criteria for Adverse Events (CTCAE). We now analyze all adverse events using CTCAE and time and severity weighted toxicity reporting method (MOSES). MATERIALS AND METHODS: MOSES was calculated separately for GI, genitourinary (GU)/GI, and any late toxicities (GI, GU, lymphedema, fatigue, vaginal stenosis, fibrosis and constitutional symptoms) by imputing proportionate time weightage to CTCAE. Cumulative MOSES (C-MOSES) for multiple system and multiorgan toxicity was determined. Difference in arms was analyzed as time-to-event and intention-to-treat analysis using CTCAE grade ≥ 1 and C-MOSES ≥ 0.70. RESULTS: We observed no difference in the 3-year cumulative incidence of CTCAE grade ≥ 1 GI, GI or GU, or any late toxicity between treatment arms. However, while using C-MOSES, HR of 0.59 (95% CI 0.38-0.92, p = 0.017), 0.68 (95% CI: 0.44-1.05, p = 0.08) and 0.72 (95% CI: 0.52-0.99, p = 0.04) was observed for GI, GI or GU, or any late toxicity within IG-IMRT respectively. CONCLUSION: This demonstrates superior discrimination of intervention effects using MOSES which demonstrates superiority of IG-IMRT.

N Gene Target Failure (NGTF) for detection of Omicron: a way out for the "stealth" too?

S-gene target failure (SGTF) is neither specific nor accurate for identification of Omicron lineage of SARS-CoV-2. We observed N-gene target failure (NGTF) in 402 out of 412 SARS-CoV2 positive cases from December to mid-January 2022 using a commercially available assay. This phenomenon was not observed with more than 15,000 cases tested previously. We sequenced the genome of five samples with NGTF and compared these results with six cases where NGTF was not seen. We confirm that cases with NGTF were the Omicron lineage while cases with preserved N-gene amplification belonged to Delta lineage. We discovered that the ERS31-33 deletion (nucleotide 28362-28370del) overlaps with N gene probe used, explaining NGTF. As the stealth Omicron variant also harbors ERS31-33 deletion, this approach will work for the detection of stealth Omicron variant as well. We suggest that NGTF can be used as a low cost, rapid screening strategy for detection of Omicron.

WORLDWIDE CASE FATALITY RATIO OF COVID-19 OVER TIME

BackgroundThe case fatality ratio (CFR) of coronavirus disease 2019 (COVID-19) has been reported to be variable among different countries and regions but few analyses have tracked this ratio worldwide over time. MethodsThe primary objective was to assess the time-course evolution of CFR of COVID-19 in all countries with available data and secondary objective was to evaluate associations between country-wise CFR and country-level health, human development, demographic and economic parameters. Day-wise data of COVID-19 cases and deaths for each country was extracted from a public repository and countries with at least 1000 cases on cutoff date were clustered by unsupervised k-means on the basis of deaths per 100000 population (DP100K). Day-wise CFR (cumulative deaths divided by cumulative cases, multiplied by 100) for each country and cluster (country group) was plotted as time-series and country-level parameters were tested for association with CFR using weighted multiple linear regression. ResultsOn September 24, 2020 there were 32140504 cumulative COVID-19 cases and 981792 deaths reported from 184 countries for a worldwide CFR of 3.06 % (95%CI 3.05 -3.07). Unsupervised k-means clustering in 157 countries with at least 1000 reported cases resulted in Clusters (country groups) A, B, C, D and E with centroid DP100K and CFR of 0.100 and 2.51 (95% CI 2.42-2.61), 0.503 and 2.28 (95% CI 2.23-2.33), 1.816 and 1.73 (95% CI 1.71-1.75), 7.395 and 1.76 (95% CI 1.75-1.76), and 36.303 and 3.82 (95% CI 3.82-3.83), respectively. In a log-log analysis DP100K and CFR were significantly positively correlated (R=0.3570, p<0.001) with each other. All country groups and majority of included countries showed a pattern of gradually increasing CFR from the beginning of pandemic, followed by a plateau and then a steady decline in CFR. Among 10 country-level parameters, GDP per capita ({beta}=-0.483, p=0.000), hospital beds per population ({beta}=-0.372, p<0.001), mortality from air pollution ({beta}=-0.487, p=0.003) and population density ({beta}=-0.570, p< 0.000) were significantly negatively associated while maternal mortality ratio ({beta}=0.431, p=0.000) and age ({beta}=0.635, p<0.000) were positively associated with CFR. ConclusionsThe CFR of COVID-19 has gradually increased over time in majority of countries at various stages of the pandemic, followed by a plateau and a steady decline. Population level COVID-19 mortality burden and CFR are significantly positively associated with each other.

Resveratrol and Copper for treatment of severe COVID-19: an observational study (RESCU 002)

BackgroundTo be universally applicable in treatment of severe COVID-19, novel therapies, especially those with little toxicity and low cost, are urgently needed. We report here the use of one such therapeutic combination involving two commonly used nutraceuticals, namely resveratrol and copper in patients with this disease. This study was prompted by pre-clinical reports that sepsis-related cytokine storm and fatality in mice can be prevented by oral administration of small quantities of resveratrol and copper. Since cytokine storm and sepsis are major causes of death in severe COVID-19, we retrospectively analyzed outcomes of patients with this condition who had received resveratrol and copper. Methods & FindingsOur analysis comprised of 230 patients with severe COVID-19 requiring inhaled oxygen who were admitted in a single tertiary care hospital in Mumbai between April 1 and May 13 2020. Thirty of these patients received, in addition to standard care, resveratrol and copper at doses of 5.6 mg and 560 ng, respectively, orally, once every 6 hours, until discharge or death. These doses were based on our pre-clinical studies, and were nearly 50 times and 2000 times less, respectively, than those recommended as health supplements. A multivariable-adjusted analysis was used to model the outcome of death in these patients and evaluate factors associated with this event. A binary logistic regression analysis was used, with age, sex, presence of comorbidities and receipt of resveratrol-copper as covariates. Data were updated as of May 30 2020. The number of deaths in resveratrol-copper and standard care only groups were 7/30 (23.3%, 95% CI 8.1%-38.4%) and 89/200 (44.5%, 95% CI 37.6%-51.3%), respectively. In multivariable analysis, age >50 years [odds ratio (OR) 2.558, 95% CI 1.454-4.302, P=0.0011] and female sex (OR 1.939, 95% CI 1.079-3.482, P=0.0267) were significantly associated, while presence of co-morbidities was not significantly associated (OR 0.713, 95% CI 0.405-1.256, P=0.2421) with death. There was a trend towards reduction in death in patients receiving resveratrol-copper (OR 0.413, 95% CI 0.164-1.039, P= 0.0604). ConclusionsWe provide preliminary results of a novel approach to the treatment of severe COVID-19 using a combination of small amounts of commonly used nutraceuticals, which is non-toxic and inexpensive, and therefore could be widely accessible globally. The nearly two-fold reduction in mortality with resveratrol-copper observed in our study needs to be confirmed in a randomized controlled trial.

High Filtration Efficiency Face Masks made from Sterilization Wraps

COVID-19 pandemic has spawned the need for mass production of N-95 respirators. We used Sterilization Wraps to produce face masks which maintained 93% particle capture efficacy post sterilization. This ubiquitously available material could be explored for production of high quality face masks at a cost less than 30 US cents.

Adjuvant chemotherapy in locally advanced cervical cancer: the ceiling remains unbroken / 부인종양

No abstract available.

Outcomes of advanced epithelial ovarian cancer with integration of metronomic chemotherapy: An Indian rural cancer centre experience.

BACKGROUND: Paclitaxel-platinum and optimal cytoreductive surgery are the standard of care for ovarian carcinoma. Poor socioeconomic profile and therapeutic constraints in rural India poses a therapeutic challenge. AIM: To evaluate outcomes of epithelial ovarian carcinoma. OBJECTIVES: To calculate disease-free survival (DFS), overall survival (OS), and factors affecting outcomes. MATERIALS AND METHODS: Data of patients diagnosed as ovarian carcinoma registered between March 2009 and March 2014 were retrieved. Demographic profile, chemotherapy and response, surgery, and disease progression were collected. Patients who underwent surgery or completed three cycles of chemotherapy were selected. Kaplan-Meir survival was used to determine disease-free and OS. Log-rank test used to evaluate factors affecting outcome. RESULTS: Median follow-up is 26 months. 93/102 patients (91%) underwent cytoreductive surgery, of which 37 had primary cytoreduction (40%) while 56 had interval cytoreduction. 21/93 (23%), 57/93 (61%), and 15/93 (16%) patients were operated by local surgeons, surgeons of our hospital, and trained oncosurgeons, respectively. Induction paclitaxel-platinum was used in 35/63 (56%) patients while 28/63 patients (44%) received neoadjuvant metronomic chemotherapy. Median DFS and OS are 17 and 54 months respectively while 3 year OS of 66%. Median DFS of patients operated by oncosurgeons versus local surgeons were 22 months versus 15 months (P = 0.01), OS was 54 versus 26 months (P = 0.01).40/88 (45%) patients received maintenance metronomic therapy after adjuvant chemotherapy with median of 6 months (range 2-18 months). Patients receiving metronomic maintenance had better DFS, 18 months versus 15 months (P = 0.69). CONCLUSION: Induction therapy in ovarian carcinoma helps in selecting patients for cytoreductive surgery. Outcomes are better if operated by trained oncosurgeons. Maintenance metronomic has potential to delay disease progression.

Brain metastasis from cervical carcinoma--a case report.

Brain metastases from cervical carcinomas are extremely rare. We report a patient with squamous cell carcinoma of the cervix who developed an isolated left parietooccipital lobe metastasis within 4 months of treatment of the primary disease. The presenting symptoms of the metastatic disease were visual disturbance, headache, and vomiting. The patient was successfully treated by surgical excision of the metastasis and adjuvant whole brain radiation therapy, and she was disease-free at the 6-month follow-up after treatment of the recurrence.