Association of PET-based estradiol-challenge test for breast cancer progesterone receptors with response to endocrine therapy

Clinical estrogen receptor (ER) testing for breast cancer is limited in predicting response to endocrine therapy (ET). In this phase 2 clinical trial, authors demonstrate that the responsiveness to ET can be predicted by use of PET/CT with 21-[18F]fluorofuranylnorprogesterone (FFNP) to detect the change in tumor progesterone receptor (PgR) levels after a one-day estradiol challenge

Factors influencing delayed clearance of high dose methotrexate (HDMTX) in pediatric, adolescent, and young adult oncology patients

PurposeTo identify modifiable risk factors associated with prolonged clearance of methotrexate in pediatric, adolescent, and young adult (AYA) oncology patients receiving high dose methotrexate (HDMTX).Design/MethodA single institution, retrospective chart review of patients receiving HDMTX between 2010-2017. Patients had a diagnosis of either leukemia or osteosarcoma. Data included demographics, concurrent intravenous (IV) medications, IV fluids (IVF) administered, urine output (UO), and rises in serum creatinine (RSC) reflective of renal toxicity (RT). Outcome measures included 1) delayed targeted MTX clearance (DC), 2) actual time to clearance (TTC) and 3) length of stay (LOS).ResultsData from 447 HDMTX administrations were analyzed. The sample consisted of 241 (54%) osteosarcoma encounters, and 206 (46%) leukemia encounters, with an average patient age of 12.7 years. Multivariate analysis showed that DC was associated with the diagnosis of leukemia (OR 7.64, p <.0001), and less UO on day 1 (OR 0.76, p=0.005). Increased TTC was associated with increasing age (RR 1.02, p<0.0001), higher 24-hour MTX levels (RR 1.001, p=0.012) and 48-hour MTX levels (RR 1.02, p<0.0001), RT (RR 1.004, p<0.0001), use of IV lorazepam (RR 1.08, p=0.001) and IV metoclopramide (RR 1.08, p<0.001) both on day 3. Like TTC, LOS was affected by MTX levels at 24 (RR 1.001, p=0.025) and 48 hours (RR 1.03, p<0.0001), RT (RR 1.006, p<0.0001), total IV medications on day 3 (RR 1.042, p<0.0001), and the use of leucovorin on day 2 (RR 0.93, p=0.002).ConclusionMultiple modifiable risk factors were identified which can be leveraged to improve HDMTX clearance. Subsequent efforts will assess whether acting on such risk factors can improve MTX clearance and shorten LOS

Transoral laser microsurgery for oral squamous cell carcinoma: Oncologic outcomes and prognostic factors

BACKGROUND: Modest survival rates are published for treatment of oral squamous cell carcinoma (OSCC) using conventional approaches. Few cohort studies are available for transoral resection of OSCC. METHODS: Analysis for recurrence, survival, and prognosis of patients with OSCC treated with transoral laser microsurgery (TLM) ± neck dissection was obtained from a prospective database. RESULTS: Ninety-five patients (71 patients had stages T1–T2 and 24 had stages T3–T4 disease) with minimum follow-up of 24 months met criteria and demonstrated negative margins in 95%. Five-year local control (LC) and disease-specific survival (DSS) were 78% and 76%, respectively. Surgical salvage achieved an absolute final locoregional control of 92%. Immune compromise and final margins were prognostic for LC, whereas T classification, N classification, TNM stage, comorbidity, and perineural invasion were also significant for DSS. CONCLUSION: We document a large series of patients with OSCC treated with TLM, incorporating T1 to T4 primaries. A significant proportion of stage III/IV cases demonstrates feasibility of TLM in higher stages, with final margin positivity of 5%, LC greater than 90%, and comparable survival outcomes

Nab-paclitaxel-based compared to docetaxel-based induction chemotherapy regimens for locally advanced squamous cell carcinoma of the head and neck

We previously reported that nab-paclitaxel-based induction chemotherapy (IC) and concurrent chemoradiotherapy resulted in low relapse rates (13%) and excellent survival in head and neck squamous cell carcinoma (HNSCC). We compare the disease-specific survival (DSS) and overall survival (OS) between patients given nab-paclitaxel, cisplatin, and fluorouracil with cetuximab (APF-C) and historical controls given docetaxel, cisplatin, and fluorouracil with cetuximab (TPF-C). Patients with locally advanced HNSCC were treated with APF-C (n = 30) or TPF-C (n = 38). After 3 cycles of IC, patients were scheduled to receive cisplatin concurrent with definitive radiotherapy. T and N classification and smoking history were similar between the two groups and within p16-positive and p16-negative subsets. The median duration of follow-up for living patients in the APF-C group was 43.5 (range: 30–58) months versus 52 (range: 13–84) months for TPF-C. The 2-year DSS for patients treated with APF-C was 96.7% [95% Confidence Interval (CI): 85.2%, 99.8%] and with TPF-C was 77.6% (CI: 62.6%, 89.7%) (P = 0.0004). Disease progression that resulted in death was more frequent in the TPF-C group (39%) compared with the APF-C group (3%) when adjusted for competing risks of death from other causes (Gray's test, P = 0.0004). In p16 positive OPSCC, the 2-year DSS for APF-C was 100% and for TPF-C was 74.6% (CI: 47.4%, 94.6%) (P = 0.0019) and the 2-year OS for APF-C was 94.1% (CI: 65.0%, 99.2%) and for TPF-C was 74.6% (CI: 39.8%, 91.1%) (P = 0.013). In p16 negative HNSCC, the 2-year DSS for APF-C was 91.7% (CI: 67.6%, 99.6%) and for TPF-C was 82.6% (CI: 64.4%, 94.8%) (P = 0.092). A 2-year DSS and OS were significantly better with a nab-paclitaxel-based IC regimen (APF-C) compared to a docetaxel-based IC regimen (TPF-C) in p16-positive OPSCC

Association of PPARγ2 polymorphisms with carcass and meat quality traits in a Pietrain x Jinhua F2 population

The PPARγ2 gene is a key regulator of both proliferation and preadipocyte differentiation in mammals. Herein its genotype and allele frequencies were analyzed using PCR-SSCP in eight pig breeds (N = 416). Two kinds of polymorphisms of the PPARγ2 gene were detected, including a previously reported shift SNP A177G (Met59Val) in exon 1 and a novel silent mutation G876A in exon 5. The results revealed that European pig breeds carry a higher allele A frequency at the A177G locus and a fixed GG genotype at the G876A locus. Allele A at the G876A locus was only found in Jinhua pigs. The association between haplotype (A177G/G876A) and carcass and meat quality traits was analyzed in a Pietrain x Jinhua F2 population (N = 248). The PPARγ2 gene was found to be significantly associated with backfat thickness at the shoulder (p < 0.05), 6–7th ribs (p < 0.01), last rib (p < 0.01), gluteus medius (p <0.05) and ham weight (p < 0.01). Significant effects of different haplotypes on ham weight and backfat thickness at the 6–7th ribs, last rib, and gluteus medius were also observed

Does DIF signal a lack of essential unidimensionality?

The majority of applied differential item functioning (DIF) studies test hypotheses regarding probability differences. The presence of DIF then is often attributed to the assumption of multidimensionality, without any empirical evidence of a demonstrable additional dimension when all that has been found is that the grouping variable influenced measurement, which any number of rival hypotheses might explain. Therefore, it is of interest to know whether DIF can manifest itself as multidimensionality through a dimensionality assessment procedure. Specifically, the current study investigated under what conditions a DIF-contaminated test could display a lack of essential unidimensionality via DIMTEST. DIF data were modeled using two simulation methods. One used Raju’s (1988) formula (item characteristic curve, ICC area difference) and the other used Shealy and Stout’s (1993a, 1993b) multidimensional model for DIF (MMD). A variety of factors were manipulated in the study (e.g., DIF magnitude, percentage of DIF items). Additionally, SIBTEST (Simultaneous Item Bias Test) was used to examine DIF conditions (modeled by both methods) with similar DIMTEST rejection rates to determine whether a MMD based DIF detection method can correctly identify known DIF items modeled by both the area difference and MMD methods. The study results suggest that a test can be contaminated with detectable DIF items but still hold essential unidimensionality. It is hoped that the study results can motivate psychometricians to revisit theoretically/methodologically/analytically/scientifically the appealing conceptualization of DIF as signaling multidimensionality and ponder important questions such as whether the influence of an external variable -group membership- equals the presence of multidimensionality, or whether rival hypotheses other than multidimensionality might explain DIF, thus affecting the very way in which DIF is conceptualized and interpreted in both applied and methodological studies, potentially having an impact on millions of test takers

Cisplatin ototoxicity: Examination of the impact of dosing, infusion times, and schedules in pediatric cancer patients

Background: Sensorineural hearing loss is a well-known side effect of cisplatin (CDDP). There is limited research on the effect of dosing, infusion times, and schedules of cisplatin administration and their impact on hearing loss. Methods: A retrospective review of 993 pediatric patients\u27 medical and audiological charts from August 1990 to March 2015 was conducted using stringent inclusion criteria to characterize patients with hearing loss. 248 of these patients received CDDP. Of these, 216 patients had sufficient CDDP infusion data to assess for sensorineural hearing loss attributable to CDDP and its associated risk factors. Chart reviews were performed to extract clinical data including CDDP dosing information. Demographic and clinical characteristics were summarized by descriptive statistics, and univariate and multivariate logistic regressions were performed to examine the relationship between hearing loss and specific parameters of cisplatin administration (amount infused per dose, prescribed infusion time, total number of doses, number of doses per cycle, number of cycles, cumulative cisplatin exposure). Stepwise variable selection procedure was performed in the multivariate model building to extract the best subset of risk factors for the prediction of hearing loss and worsening ototoxicity grade using an established ototoxicity grading scale from the International Society of Pediatric Oncology (SIOP). Results: A total of 153 patients with complete medical and audiologic data were evaluable for analysis. Hearing loss was identified in 72.6% of the patients. Multivariate analysis revealed that age [OR=0.90 (0.84-0.97), Conclusion: In one of the largest studies examining the influence of CDDP dosing and schedules on hearing loss, we found the amount of CDDP infused per dose is a significant risk factor. Considerations in designing regimens that reduce the amount of CDDP infused per dose may reduce the risk of hearing loss. Randomized prospective trials are needed

Stereoselective bioaccumulation and degradation of chiral pesticide hexythiazox in earthworm-soil microcosm

The chiral pesticide hexythiazox was extensively employed in agricultural activities and has garnered growing concern for its harmful impact on the ecosystem. This study investigates the toxicodynamic earthworm at the enantiomeric level of hexythiazox. Earthworms exhibited notable enantioselectivity during the accumulation stage. Furthermore, the presence of earthworms can impact the rate of degradation and enantioselectivity of hexythiazox in soil. The accumulation of the two hexythiazox enantiomers in the earthworm adhered to the one-compartment model, whereas the elimination phase was governed by the first-order kinetics equation. Furthermore, it was discovered that there was no notable enantioselectivity observed during the elimination phase