Efficacy of Oral SERDs in the treatment of ER+, HER2 - metastatic breast cancer, a stratified analysis of the ESR1 wild type and mutant subgroups.

BACKGROUND: Oral SERDs are a novel drug class that have been developed to counteract resistance due to ESR1 mutations. Several SERDs have emerged from phase 2 and 3 trials, with the FDA limiting approval for Elacestrant to patients with ESR1mt tumours despite PFS benefit in the overall population. However, questions remain on whether patients with ESR1wt tumours stand to benefit from oral SERDs. PATIENTS AND METHODS: Manuscripts and conference presentations of Randomised Controlled Trials were extracted after a systematic search of Embase, PubMed and Cochrane from inception until January 21,2023. RCTs investigating the efficacy of oral SERDs versus endocrine therapy for ER positive, HER2 negative advanced breast cancer, and which reported the Kaplan Meier (KM) curves of PFS in the overall and ESR1 mutant (ESR1mt) population were selected. A graphical reconstructive algorithm was applied to estimate time-to-event outcomes from reported KM curves in all overall and ESR1mt cohorts. A bipartite matching algorithm, KMSubtraction, was used to derive survival data for unreported (ESR1wt) subgroups. An individual patient data (IPD) meta-analysis was then pursued, pooling data by ESR1 mutation status in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane Guidelines for IPD. RESULTS: The randomized clinical trials ACELERA, AMEERA-3, EMERALD and SERENA-2 were included, totalling 1290 patients. In the pooled analysis of the overall cohort, PFS benefit was observed with oral SERDs when compared with treatment of physicians choice (TPC) (HR 0.783, 95%CI 0.681-0.900, p<0.001). In the ESR1mt subgroup, oral SERDs demonstrated improved PFS (HR 0.557, 95%CI 0.440-0.705, p<0.001) compared to TPC. In the ESR1wt subgroup, oral SERDs demonstrated no significant PFS benefit (HR 0.944, 95%CI 0.783-1.138, p=0.543) when compared to TPC. CONCLUSIONS: The results of this IPD meta-analysis suggests that PFS benefit in the overall population is mainly driven by the ESR1mt subgroup.

Antimicrobial stewardship programs in emergency departments: how do we measure antimicrobial use? A systematic review.

OBJECTIVE: The implementation of antimicrobial stewardship programs (ASPs) has become a usual practice in hospital settings. However, the method for monitoring antimicrobial use in accident and emergency departments (ED) is not yet adequately defined. Thus, the objective of this review is to describe antimicrobial use indicators used by ASPs implemented in ED. METHODS: A systematic review was performed based on studies found in the following academic research databases: MEDLINE, EMBASE, Web of Science, and Scopus (Period: January 2000 to December 2019). Controlled clinical trials, before-and-after studies, interrupted time series, and repeated measures studies assessing the impact of ASPs on antimicrobial use in ED were included; studies published in languages other than English or Spanish were excluded from this review. RESULTS: Twenty-six studies met the inclusion criteria and were included in this systematic review. In total, 15 (62.5%) studies described the ASP team members who collaborated with the ED staff. Most (21; 80.8%) studies used the percentage of patients with an antibiotic prescription as an indicator. Four (15.4%) studies included defined daily dose data. The antibiotic treatment duration was reported in four (15.4%) studies. Only two studies assessed the impact of the ASP using microbiological indicators, both of which used the incidence of infection with Clostridioides difficile as the indicator. CONCLUSIONS: The reports of experiences in implementing ASPs in ED show heterogeneous antimicrobial use indicators, which makes it difficult to compare results. Therefore, antimicrobial use indicators for ASPs must be standardised between hospital units.

Epidemiology of tuberculosis and HIV coinfections in Singapore, 2000-2014.

Cross-matching of records between Singapore's tuberculosis and HIV registries showed that 3.3% of individuals with tuberculosis (TB) were coinfected with HIV (2000-2014), the TB incidence among individuals with HIV infection was 1.65 per 100 person-years, and 53% of coinfections were diagnosed within 1 month of each other. The findings supported joint prevention programmes for early diagnosis and treatment.

Aligned carbon nanotubes on quartz substrate for liquid gated biosensing.

A facile and high performance biosensing platform using aligned carbon nanotubes on quartz substrate is reported in this communication. Single walled carbon nanotubes are grown on quartz substrates by a chemical vapor deposition process and are characterized with field emission scanning electron microscopy and atomic force microscopy in order to verify the quality of the material. The quartz substrate is then directly used as a biosensor in a field effect transistor configuration. In order to demonstrate the sensing capabilities of the fabricated sensor devices, electronic detection of prostate specific antigen, a potential cancer biomarker, is carried out by adopting liquid gated configuration. A conductivity change due to the specific binding of target antigen with the immobilized receptor antibody demonstrates the sensing capabilities of the fabricated device. Sub-nM detection sensitivities have been obtained using the adopted direct immunoassay approach, which shows that the device responds to clinically relevant concentration regimes.

Comparison of the single-use LMA supreme with the reusable ProSeal LMA for anaesthesia in gynaecological laparoscopic surgery.

The Laryngeal Mask Airway Supreme (LMAS) is a new, single-use laryngeal mask airway with gastric access. We conducted a randomised controlled study comparing the LMAS with the reusable ProSeal Laryngeal Mask Airway (PLMA) in 70 patients undergoing general anaesthesia with paralysis for gynaecological laparoscopic surgery. Our primary outcome measure was the oropharynegal leak pressure. We also compared the two devices for ease of insertion, adequacy of ventilation and incidence of complications. Both devices had similar rates of successful insertion at the first attempt (LMAS 94% vs PLMA 91%). There was no difference in the time to establish an effective airway (LMAS 25 +/- 22 vs PLMA 24 +/- 9 seconds), although gastric tube insertion was faster for the LMAS (5 +/- 1 vs 7 +/- 3 seconds, P < 0.001). The mean oropharyngeal leak pressure in the LMAS was significantly lower than in the PLMA (27.9 +/- 4.7 vs 31.7 +/- 6.3 cmH2O, P = 0.007). This was consistent with a lower maximum tidal volume achieved with the LMAS (481 +/- 76 vs 515 +/- 63 ml, P = 0.044). We found that after 60 minutes the cuff pressure was significantly higher in the PLMA (110 +/- 21 vs 57 +/- 8 cmH2O, P < 0.001). There was no difference in the ability to provide adequate ventilation and oxygenation during anaesthesia. Complication rates were similar We conclude that the oropharyngeal leak pressure and the maximum achievable tidal volume are lower with the LMAS than with the PLMA.

Outcomes of adjuvant chemoradiotherapy after a radical gastrectomy and a D2 node dissection for gastric adenocarcinoma.

PURPOSE: Intergroup 0116 (INT-0116) established adjuvant chemoradiation as the standard of care for resected high-risk adenocarcinoma of the stomach in the United States. However, adjuvant chemoradiation remains controversial in many parts of Asia and Europe, where patients tend to undergo a more thorough D2 dissection. In INT-0116, 90% of patients had a limited or inadequate node dissection (D0 or D1). Also, 17% of patients in the chemoradiation arm had to discontinue treatment because of toxicities. The objectives of this retrospective study are to report the clinical outcomes of a cohort of patients who were mostly treated with a D2 node dissection and received adjuvant chemoradiation as per INT-0116, and the toxicities of chemoradiation in the context of more aggressive surgery. METHODS: After the results of INT-0116 became apparent, we adopted an institutional policy whereby patients who would otherwise fit the inclusion criteria of INT-0116 received adjuvant chemoradiation. Between March 1999 and November 2004, 70 consecutive patients with pathologic stage T3, T4, or node-positive disease were treated according to the chemoradiation arm of INT-0116. Patients received intravenous 5-fluorouracil 425 mg/m and leucovorin 20 mg/m in cycles 1, 3, and 4. Concurrent chemoradiation was given in cycle 2 and consisted of bolus 5-fluorouracil and leucovorin and radiotherapy (45 Gy over 25 fractions in 5 weeks). All patients were operated on by dedicated Japan-trained Surgical Oncologists. RESULTS: Sixty-seven patients (96%) had a D2 nodal dissection. Sixty-five patients (93%) had negative pathologic margins (R0 resection) and 5 (7%) had microscopically involved margins (R1 resection). The median follow-up was 27 months (range, 10.1-60.3). The 3-year overall survival, disease-free survival, and local control were 60.6%, 54.1%, and 84.3%, respectively. Of the 30 patients who relapsed, 5 (17%) had isolated locoregional recurrences only. The National Cancer Institute--Common Terminology Criteria version 3.0 acute grade 3 or 4 gastrointestinal and hematological toxicity rates were 15.7% and 4.3%, respectively. Toxicities led to chemotherapy dose-reductions in 18 patients and dose-delay in 19 patients. Including chemotherapy dose-reductions and delays, 66 patients (94%) completed the entire chemoradiation regimen. There were no toxicity-related deaths. CONCLUSION: In our cohort of 70 patients who had a more thorough D2 node dissection, adjuvant chemoradiation was well tolerated with acceptable toxicities and reasonable tumor control.

Cancer care in Singapore.

Singapore is a small country, but it is ideally and centrally located to conveniently serve not only its population but also patients from the surrounding regions. It's economy is sufficiently strong to maintain highly sophisticated and expensive equipment to manage a high level of healthcare, including oncology services.Cancer incidences in Singapore are on an upward trend based on the report of the Singapore Cancer Registry for the period of 2001-2005. Cancer is the number one cause of death in Singapore. The three most common cancers for males in Singapore, in decreasing occurrences, are colorectal, lung, and prostate. For females, the three most common cancers are breast, colorectal, lung cancers. Technological advances and advances in anti-cancer drugs have transformed cancer management leading to improved outcomes worldwide and in Singapore as well. The epidemiology and management of these common cancers in Singapore are presented. While Singapore presently has five radiotherapy centres (3 public, 2 private) to service its population of 4.5 million and regional needs, the government has plans to expand its radiotherapy services to accommodate the aging population and the rising expectations of increasingly affluent cancer patients seeking advanced cancer care. The current and future initiatives spearheaded by Singapore to achieve excellence in this aspect are discussed.