bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the efficacy of posterior-anterior screws, anterior-posterior screws and a posterior-anterior plate in the fixation of posterior malleolar fractures with a fragment size of ≥ 15 and < 15%
Authors: Wang Zheng , Sun Jianbin , Yan Jun , Gao Pengcheng , Zhang Hao , Yang Yong , Jin Qunhua
Published: August 2020

Background

Different fixation methods have been used to treat posterior malleolar fractures (PMFs), but the clinical efficacy of different fixation methods in the treatment of PMF with different fragmentation has rarely been reported. The purpose of this study was to investigate the efficacy of posterior-anterior (PA), anterior-posterior (AP) screws and PA plate in the fixation of PMFs with a fragment size of ≥15 and < 15%.

Methods

This is a retrospective study of the clinical data of 243 patients with a unilateral ankle fracture involving the posterior malleolar ankle fracture. All patients were divided into two groups based on their fragment size, ≥15% (n = 136) and < 15% (n = 107). After reduction of PMF under direct vision via a posterolateral approach, posterior-anterior (PA), anterior-posterior (AP) screws and PA plate were used for fixation of PMF in the two groups. Briefly, for fixation of PMF with PA screw, two to three 3.5-mm (Depuy Synthes, Switzerland) cannulated screws were placed from the posterior to anterior direction; for fixation with PA plate, a 3.5-mm reconstruction plate (Depuy Synthes, Switzerland) was placed from the posterior to anterior direction, and for fixation of PMF with an AP screw, two to three 3.5-mm screws were placed from the anterior to posterior direction. All patients were followed up at 1, 3, 6, and 12 months after surgery and thereafter at 6-month intervals. The primary outcomes were AOFAS and ROM, which were recorded at the final follow-up.

Results

The average follow-up time for all patients was 18.9 months (range 12–36 months), and all fractures healed. In fragment size ≥15% group, the average AOFAS score of patients treated with PA, AP screws and posterior plate were 91.5, 91.8, and 90.8, respectively, and the average limited ankle-dorsiflexion ROM was 5.0 °, 5.4 ° and 5.6°, respectively, at the last follow-up, there was no significant difference between the three fixation methods in terms of AOFAS scores and ankle ROM (P > 0.05). In fragment size < 15% group, the average AOFAS score of patients treated with PA, AP screws and posterior plate were 92.3, 91.9, and 84.1, respectively, the average limited ankle-dorsiflexion ROM were 5.1 °, 4.7 °, and 6.3 °, respectively, at the last follow-up. There were statistically significant differences in AOFAS scores and ankle ROM between posterior plate fixation and PA, AP screw fixation (P < 0.05); while no significant difference was found between PA and AP screw fixation (P > 0.05).

Conclusion

For PMFs with fragment size ≥15%, there was no significant difference in the outcomes between the three fixation methods. For PMF with fragmentation < 15%, the PA and AP screws both provided good fixation.
Integrated analysis of RNA-binding proteins in human colorectal cancer
Authors: Fan Xuehui , Liu Lili , Shi Yue , Guo Fanghan , Wang Haining , Zhao Xiuli , Zhong Di , Li Guozhong
Published: August 2020

Background

Although RNA-binding proteins play an essential role in a variety of different tumours, there are still limited efforts made to systematically analyse the role of RNA-binding proteins (RBPs) in the survival of colorectal cancer (CRC) patients.

Methods

Analysis of CRC transcriptome data collected from the TCGA database was conducted, and RBPs were extracted from CRC. R software was applied to analyse the differentially expressed genes (DEGs) of RBPs. To identify related pathways and perform functional annotation of RBP DEGs, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out using the database for annotation, visualization and integrated discovery. Protein-protein interactions (PPIs) of these DEGs were analysed based on the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized by Cytoscape software. Based on the Cox regression analysis of the prognostic value of RBPs (from the PPI network) with survival time, the RBPs related to survival were identified, and a prognostic model was constructed. To verify the model, the data stored in the TCGA database were designated as the training set, while the chip data obtained from the GEO database were treated as the test set. Then, both survival analysis and ROC curve verification were conducted. Finally, the risk curves and nomograms of the two groups were generated to predict the survival period.

Results

Among RBP DEGs, 314 genes were upregulated while 155 were downregulated, of which twelve RBPs (NOP14, MRPS23, MAK16, TDRD6, POP1, TDRD5, TDRD7, PPARGC1A, LIN28B, CELF4, LRRFIP2, MSI2) with prognostic value were obtained.

Conclusions

The twelve identified genes may be promising predictors of CRC and play an essential role in the pathogenesis of CRC. However, further investigation of the underlying mechanism is needed.
Investigation of the SPAG5 gene expression and amplification related to the NuMA mRNA levels in breast ductal carcinoma
Authors: Mohamadalizadeh-Hanjani Zeinab , Shahbazi Shirin , Geranpayeh Loabat
Published: August 2020

Background

The cell proliferative markers are very important in breast cancer. Since SPAG5 and NuMA proteins play a significant role in the mitosis regulatory network and cell division, we aimed to study their mRNA levels as well as SPAG5 gene amplification correlated to clinicopathological status in ductal carcinoma of the breast.

Methods

SPAG5 and NuMA gene expressions were investigated in 40 breast cancer tissues and normal adjacent tissues via real-time PCR. PUM1 was selected as the reference gene. QMF PCR method was applied to study SPAG5 gene amplification and AGBL2, BOD1L, and POR were designated as internal control genes. Gene amplification was determined by calculating a dosage quotient for each DNA fragment.

Results

Increased SPAG5 mRNA expression was detected in breast cancer tissues (p = 0.005) and related to tumor size. No significant difference was observed between NuMA gene expression level in tumor tissue and the normal adjacent tissue (p = 0.56). However, we observed that NuMA expression was significantly increased in ER-positive tumor tissues. There was no clear correlation pattern between SPAG5 and NuMA mRNA levels (r = 0.33). Seventeen percent of tissues showed complete amplification in SPAG5 gene fragments.

Conclusion

Our results were consistent with the previous publications regarding SPAG5 gene expression and amplification in breast cancer with an emphasis on the prominent role of this protein in tumor pathogenesis. Our results failed to yield any correlation between SPAG5 and NuMA mRNA levels which implies independence of these genes in breast cancer pathogenesis.
Caring for cancer patients in the Covid pandemic: choosing between the devil and deep sea
Authors: Chakraborty Mainak , Pandey Manoj
Published: August 2020

Background

Healthcare is an essential service at any time more so in the crisis like Covid. With increase in number of cases and mortality from Covid, the primary focus is shifted to the management of the Covid crisis and other health emergencies thus affecting normal health services and routine treatment of other diseases like cancer.

Methods

This article reviews the published literature and guidelines on Covid and cancer and discusses them to optimize the care of cancer patients during Covid pandemic to improve treatment outcomes.

Results

The results of the review of published literature show a twofold increase in probability of getting CoV2 infection by the cancer patients and a four-fold increase in chance of death. On the other hand, if left untreated a 20% increase in cancer death is expected. Data further show that none of the medicines like remdesivir, hydroxy chloroquin, dexamethasone, or azithromycin improves survival and response to Covid in cancer patients. Surgical results too show similar outcome before and after the pandemic though most of these report on highly selected patients populations.

Conclusions

The Covid 2019 pandemic places cancer patients in a very difficult situation wherein if they seek treatment, they are exposing themselves to a risk of developing CoV2 infection and if they do not, the probability of dying without treatment increases. Hence, for them it is a choice between the devil and deep sea, and it is for the healthcare providers to triage patients and treat who cannot wait even though the data from the carefully selected cohort of patients show no increase in mortality or morbidity from treatment during Covid.
Anti-inflammatory IL-10 administration rescues depression-associated learning and memory deficits in mice
Authors: Worthen Ryan J. , Garzon Zighelboim Susan S. , Torres Jaramillo Camila S. , Beurel Eleonore
Published: August 2020

Background

Major depressive disorder is a widespread mood disorder. One of the most debilitating symptoms patients often experience is cognitive impairment. Recent findings suggest that inflammation is associated with depression and impaired cognition. Pro-inflammatory cytokines are elevated in the blood of depressed patients and impair learning and memory processes, suggesting that an anti-inflammatory approach might be beneficial for both depression and cognition.

Methods

We subjected mice to the learned helplessness paradigm and evaluated novel object recognition and spatial memory. Mice were treated with IL-10 intranasally or/and microglia cells were depleted using PLX5622. Statistical differences were tested using ANOVA orttests.

Results

We first established a mouse model of depression in which learning and memory are impaired. We found that learned helplessness (LH) impairs novel object recognition (NOR) and spatial working memory. LH mice also exhibit reduced hippocampal dendritic spine density and increased microglial activation compared to non-shocked (NS) mice or mice that were subjected to the learned helpless paradigm but did not exhibit learned helplessness (non-learned helpless or NLH). These effects are mediated by microglia, as treatment with PLX5622, which depletes microglia, restores learning and memory and hippocampal dendritic spine density in LH mice. However, PLX5622 also impairs learning and memory and reduces hippocampal dendritic spine density in NLH mice, suggesting that microglia in NLH mice produce molecules that promote learning and memory. We found that microglial interleukin (IL)-10 levels are reduced in LH mice, and IL-10 administration is sufficient to restore NOR, spatial working memory, and hippocampal dendritic spine density in LH mice, and in NLH mice treated with PLX5622 consistent with a pro-cognitive role for IL-10.

Conclusions

Altogether these data demonstrate the critical role of IL-10 in promoting learning and memory after learned helplessness.
A ubiquitous subcuticular bacterial symbiont of a coral predator, the crown-of-thorns starfish, in the Indo-Pacific
Authors: Wada Naohisa , Yuasa Hideaki , Kajitani Rei , Gotoh Yasuhiro , Ogura Yoshitoshi , Yoshimura Dai , Toyoda Atsushi , Tang Sen-Lin , Higashimura Yukihiro , Sweatman Hugh , Forsman Zac , Bronstein Omri , Eyal Gal , Thongtham Nalinee , Itoh Takehiko , Hayashi Tetsuya , Yasuda Nina
Published: August 2020

Background

Population outbreaks of the crown-of-thorns starfish (Acanthaster plancisensu lato; COTS), a primary predator of reef-building corals in the Indo-Pacific Ocean, are a major threat to coral reefs. While biological and ecological knowledge of COTS has been accumulating since the 1960s, little is known about its associated bacteria. The aim of this study was to provide fundamental information on the dominant COTS-associated bacteria through a multifaceted molecular approach.

Methods

A total of 205 COTS individuals from 17 locations throughout the Indo-Pacific Ocean were examined for the presence of COTS-associated bacteria. We conducted 16S rRNA metabarcoding of COTS to determine the bacterial profiles of different parts of the body and generated a full-length 16S rRNA gene sequence from a single dominant bacterium, which we designated COTS27. We performed phylogenetic analysis to determine the taxonomy, screening of COTS27 across the Indo-Pacific, FISH to visualize it within the COTS tissues, and reconstruction of the bacterial genome from the hologenome sequence data.

Results

We discovered that a single bacterium exists at high densities in the subcuticular space in COTS forming a biofilm-like structure between the cuticle and the epidermis. COTS27 belongs to a clade that presumably represents a distinct order (so-called marine spirochetes) in the phylumSpirochaetesand is universally present in COTS throughout the Indo-Pacific Ocean. The reconstructed genome of COTS27 includes some genetic traits that are probably linked to adaptation to marine environments and evolution as an extracellular endosymbiont in subcuticular spaces.

Conclusions

COTS27 can be found in three allopatric COTS species, ranging from the northern Red Sea to the Pacific, implying that the symbiotic relationship arose before the speciation events (approximately 2 million years ago). The universal association of COTS27 with COTS and nearly mono-specific association at least with the Indo-Pacific COTS provides a useful model system for studying symbiont-host interactions in marine invertebrates and may have applications for coral reef conservation.
Protoblock - A biological standard for formalin fixed samples
Authors: Flores Bueso Yensi , Walker Sidney P. , Hogan Glenn , Claesson Marcus J. , Tangney Mark
Published: August 2020

Background

Formalin-fixed, paraffin-embedded (FFPE) tissue is the gold standard in pathology tissue storage, representing the largest collections of patient material. Their reliable use for DNA analyses could open a trove of potential samples for research and are currently being recognised as a viable source material for bacterial analysis. There are several key features which limit bacterial-related data generation from this material: (i) DNA damage inherent to the fixing process, (ii) low bacterial biomass that increases the vulnerability to contamination and exacerbates the host DNA effects and (iii) lack of suitable DNA extraction methods, leading to data bias. The development and systematic use of reliable standards is a key priority for microbiome research. More than perhaps any other sample type, FFPE material urgently requires the development of standards to ensure the validity of results and to promote reproducibility.

Results

To address these limitations and concerns, we have developed the Protoblock as a biological standard for FFPE tissue-based research and method optimisation. This is a novel system designed to generate bespoke mock FFPE ‘blocks’ with a cell content that is user-defined and which undergoes the same treatment conditions as clinical FFPE tissues. The ‘Protoblock’ features a mix of formalin-fixed cells, of known number, embedded in an agar matrix which is solidified to form a defined shape that is paraffin embedded.

The contents of various Protoblocks populated with mammalian and bacterial cells were verified by microscopy. The quantity and condition of DNA purified from blocks was evaluated by qPCR, 16S rRNA gene amplicon sequencing and whole genome sequencing. These analyses validated the capability of the Protoblock system to determine the extent to which each of the three stated confounding features impacts on eventual analysis of cellular DNA present in FFPE samples.

Conclusion

The Protoblock provides a representation of biological material after FFPE treatment. Use of this standard will greatly assist the stratification of biological variations detected into those legitimately resulting from experimental conditions, and those that are artefacts of the processed nature of the samples, thus enabling users to relate the outputs of laboratory analyses to reality.
Innate immune response in neuronopathic forms of Gaucher disease confers resistance against viral-induced encephalitis
Authors: Melamed Sharon , Avraham Roy , Rothbard Deborah E. , Erez Noam , Israely Tomer , Klausner Ziv , Futerman Anthony H. , Paran Nir , Vitner Einat B.
Published: August 2020

Both monogenic diseases and viral infections can manifest in a broad spectrum of clinical phenotypes that range from asymptomatic to lethal, suggesting that other factors modulate disease severity. Here, we examine the interplay between the genetic neuronopathic Gaucher’s disease (nGD), and neuroinvasive Sindbis virus (SVNI) infection. Infection of nGD mice with SVNI had no influence on nGD severity. However, nGD mice were more resistant to SVNI infection. Significantly different inflammatory responses were seen in nGD brains when compared with SVNI brains: the inflammatory response in the nGD brains consisted of reactive astrocytes and microglia with no infiltrating macrophages, but the inflammatory response in the brains of SVNI-infected mice was characterized by infiltration of macrophages and altered activation of microglia and astrocytes. We suggest that the innate immune response activated in nGD confers resistance against viral infection of the CNS.
Using machine learning techniques to predict the cost of repairing hard failures in underground fiber optics networks
Authors: Nyarko-Boateng Owusu , Adekoya Adebayo Felix , Weyori Benjamin Asubam
Published: August 2020

Fiber optics cable has been adopted by telecommunication companies worldwide as the primary medium of transmission. The cable is steadily replacing long-haul microwave, copper cable, and satellite transmissions systems. Fiber cable has been deployed in an underground, submarine, and aerial architecture to transmit high-speed signals in intercontinental, inter countries, inter cities and intra-cities. Underground fiber cable transmission has experienced major failures as compared to other mediums of fiber transmission infrastructure. The failure is rampant, and especially the cable get cuts frequently in areas where there are road constructions, road road expansion projects, and other developmental projects. The cost of repairing these failures is enormous, and it largely depends on the cause of failure and the geographical area the faults occurred. The main aim of this paper was to investigate the cost of repairing underground fiber cable failures, clustered the cause of faults, and then used feedforward neural networks (FFNN) and linear regression to predict the cost of repairing future faults. The result of the predictive model is significant to the telecommunications industry, which means the cost of repairing an underground optical networks will be known to the industry players before the fault occurs. depending on which area, the cause of the failure and the mean time to repair (MTTR), the predictive model tells the mobile network operators the cost involved to repair the damaged cable. The accuracy of the result obtained indicates the predictive model is good for predicting the cost of repairing fiber cable cut in underground optical networks.
Breast cancer with an intraductal component that was proven genetically to be metastasis of contralateral breast cancer: a case report
Authors: Shinden Yoshiaki , Saho Hazuki , Nomoto Yuki , Nagata Ayako , Minami Koji , Nakajo Akihiro , Akahane Toshiaki , Hiraki Tsubasa , Tanimoto Akihide , Owaki Tetsuhiro , Kijima Yuko , Natsugoe Shoji
Published: August 2020

Background

When diagnosing patients with bilateral breast cancer, it is challenging to determine the relationship between multiple breast cancer lesions at the individual patient level with certainty.

Case presentation

A 35-year-old Japanese woman was diagnosed with a left breast cancer. She was previously diagnosed with right pT3N3M0 stage IIIC breast cancer and underwent chemotherapy with targeted therapy, radiotherapy, and endocrine therapy as adjuvant treatment after mastectomy and axillary lymph node dissection. Approximately 2 years after the first surgery, her left breast cancer was preoperatively diagnosed as a contralateral primary breast cancer, and left mastectomy and axillary lymph node dissection were performed. Histopathologically, the tumor was determined to be invasive ductal carcinoma accompanied with several intraductal components. After a second surgery, mutation analysis of her bilateral breast cancer was performed in a clinical study, which revealed that her metachronous bilateral breast tumors had the same GATA3 and CSMD1 mutations. Thus, mutation analysis strongly supported her latter left breast cancer being a metastatic lesion from the former right breast cancer. Some difficulties in diagnosing bilateral breast cancer exist when determining whether they are double primary cancers or represent contralateral breast metastasis. The existence of intraductal components is a critical piece of information for suspecting primary lesions. However, this case demonstrated that metastatic contralateral breast lesions can have intraductal components.

Conclusion

Herein we report a genetically proven contralateral breast metastasis with some intraductal components.
The “dating game”: age differences at first sex of college students in Italy
Authors: Carella Maria , García-Pereiro Thaís , Pace Roberta , Paterno Anna
Published: August 2020

Researchers have devoted much attention both to the analysis of the first sexual experience and to how the couple was established, but little is still known about age differences of partners at their first sexual relationship. The availability of two highly comparable waves of a survey on the sexual behavior of college students in Italy (SELFY—Sexual and Emotional LiFe of Youth) carried out in 2000 and 2017 allowed us to study the predictors of age differences between partners at first sex, filling the existing gap on recent research. Results of multivariate analyses show important gender differences on mate selection: women tend to choose an older partner for having their first sexual experience and are less likely as men to be involved in age discordant first sex relationships with a younger partner. Age gaps between partners also influence age at sexual debut, which tends to occur earlier in a relationship with an older partner and later if having first sex with a younger partner. Another important predictor of the age gap is the type of relationship that linked the respondent to its partner at first sex. Our estimations indicate a lower likelihood of having had an older first sex partner for students who had their first sexual experience with the own boy/girl-friend or with a friend compared to those who have had it with a stranger. Finally, we have found a higher likelihood of first sex relationships among same-age partners relative to older partners through SELFY waves and small changes on variables influencing such relationships.
A randomized trial in ovarian cancer (OC) of early treatment of relapse based on CA125 level alone versus delayed treatment based on conventional clinical indicators (MRC OV05/EORTC 55955 trials)
Authors: Rustin G. J. , van der Burg M. E.
Published: August 2020

1

The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology.

No significant financial relationships to disclose.
Impact of radiofrequency ablation therapy for breast cancer in nipple-areolar complex
Authors: Kusama M. , Imamura Y.
Published: August 2020

e11511

Background: Preservation of the safety surgical margin is difficult in BCT of a breast cancer in the vicinity of the nipple-areola complex, and mastectomy is required even for tiny tumors, with consequent poor cosmetic efects. Radiofrequency ablation (RFA) is an advanced, minimally invasive technique for breast cancer. Its application for the tumor in the nipple-areola region has recieved considerable interest. Methods: RFA of 32 malignant lesion was performed in 30 patients with nipple-areolar breast cancer (Tis: 4, T1: 18; T2: 8). One of the patients had received preoperative chemotherapy. And one patient was male breast cancer(T2).Surgery was performed on an outpatient basis.A 19-gauge cooled-tip needle was used in all cases. About 10–20ml of 5% glucose solutions was injected between the nipple-areola and the tumor before RFA to maintain a space to avoid heat damage that can occur due to diffusion of RF waves. RFA was continued until the moisture of the tumor was vaporized. This required an average of 4.3 sessions. Irradiation of radiofrequency with a boost was conducted in 23 patients. All patients were reviewd at, one month and every three monthe thereafter with US.The follow-up was complete and the median follow-up was 13months(6–30). Results: In one patient, who had undergone preoperative chemotherapy was observed a recurrence in the nipple on 9 months later, but disappeared after a second ablation of RF. Cosmetic features were maintained after surgery, except in the case that received preoperative chemotherapy, in which a mild deformity in the nipple was evident. There has been no recurrence in the 29 primary cases over a relatively short observation period. Conclusions: RFA enables treatment of breast cancer in the nipple-areolar region without damage to the surrounding tissues and degradation of cosmetic features.

No significant financial relationships to disclose.
The relationship between adherence to adjuvant hormonal therapy and survival among low-income, insured women with primary breast cancer
Authors: Kimmick G. G. , Camacho F. , Hwang W. , Anderson R. T.
Published: August 2020

e11522

Background: Clinical trials and meta-analyses show that adjuvant hormonal therapy for hormone receptor positive breast cancer significantly decreases risk of death. We explored the relationship between adherence to adjuvant hormonal therapy and death in a low-income, Medicaid-insured population. Methods: Using a Medicaid claims-tumor registry linked database and National Death Index data (NDI), we evaluated adherence to adjuvant hormonal therapy [defined as >80% Medication Possession Ratio (MPR)] and mean six-year overall and cancer-specific survival by local versus regional stage for all female breast cancer diagnosed in years 2000–2002, in North Carolina. The Kaplan-Meier and Cox Proportional Hazards models were used to determine the role of adherence on cancer-specific survival. Models were adjusted for age, race, Charlson comorbidity score, number of prescription medications, type of surgery, use of radiation therapy, prior chemotherapy, hormone receptor status (positive or unknown). Results: The final sample consisted of 1,042 cases [ages range 29–97 years (mean 65.9 years; 56% Caucasian; mean Charlson comorbidity score 4.1 (SD 2.9); 680 local and 362 regional stage], of which 732 filled a prescription for adjuvant hormonal therapy within the year after breast cancer diagnosis. Filling a prescription for adjuvant hormonal therapy, versus not, was not significantly associated with cancer-related death: HR 1.04 (95% CI 0.66 - 1.64) overall; HR 0.75 (95% CI 0.39 - 1.43) for local stage and HR 1.01 (95% CI 0.51 - 2.00) for regional stage. However, adherence in the highest quartile (MPR>95) is associated with an increase in mortality risk. Conclusions: In this low income insured group of breast cancer patients, no statistically significant association was found between death rates and use of adjuvant hormonal therapy. However, an unexpected association between very high adherence and increase in mortality was found. This may reflect methodological limitations of claims data involving bias and unidentified patient risk. More research is needed to explore reasons for higher mortality among low-income women with high medication adherence.

[Table: see text]
A phase II study of docetaxel followed by vinorelbine and doxorubicin in the neoadjuvant treatment of locally advanced breast cancer
Authors: Youssef A. C.
Published: August 2020

e11542

Background: Neoadjuvant treatment has become a standard of care for inoperable breast cancer patients. Docetaxel combination regimens have shown significant activity in this setting. We evaluated a sequential regimen of docetaxel followed by combination vinorelbine-doxorubicin as neoadjuvant treatment for locally advanced breast cancer. Primary objective is the pathological complete response (pCR) rate. Secondary objectives are the clinical response rate, the resectability rate and the safety profile. Methods: This is a prospective, open-label, phase II study. Patients with locally advanced breast cancer (T3+ or T4 M0) and no prior chemotherapy were eligible. All patients received 3 cycles of docetaxel 100 mg/m2 on d1 every 3 weeks. Patients with clinical complete response (CR) had breast cancer surgery. The remaining patients received 3 cycles of vinorelbine-doxorubicin (vinorelbine 25 mg/m2 on d1 and d8 plus doxorubicin 50 mg/m2 on d1) q3w followed by surgery if responding to treatment. Response assessment was by RECIST. Toxicity was evaluated according to NCI-CTC AE, version 3.0. Results: Out of 90 recruited patients, 50 were evaluable at the time of this analysis. Twenty-three patients (46%) had clinical CR after 3 cycles of docetaxel and underwent breast surgery. Of the remaining 27 patients (54%) who received 3 cycles of vinorelbine-doxorubicin, 10 achieved a clinical CR. Conservative surgery was performed in 44 patients (88%), and 4 had a radical mastectomy. A pCR was seen in 19 patients (38%) and a pPR in 29 patients (58%) for a 96% pathological response rate. The most common grade 2 and 3 toxicities, during docetaxel treatment were nausea and vomiting (32%/34%), neutropenia (36%/50%) and alopecia (48%/68% grade 1 and 2). The most common grade 2 and 3 toxicities during vinorelbine-doxorubicin were respectively, neuropathy (41%/52%), nausea and vomiting (63%/74%), constipation (11%/29%) and alopecia (44%/74% grade 1 and 2). Conclusions: Preliminary results show the efficacy of sequential docetaxel followed by vinorelbine-doxorubicin in inoperable breast cancer patients, with a higher rate of conservative surgery and a manageable toxicity profile. Long term follow-up is needed.

No significant financial relationships to disclose.
Anti-Mullerian hormone (AMH) and ovarian function in young breast cancer (BC) women receiving adjuvant chemoterapy (CT)
Authors: Giraudi S. , Marroni P. , Boni L. , Bighin C. , Levaggi A. , Bini G. , Taveggia P. , Venturini M. , Pronzato P. , Del Mastro L.
Published: August 2020

e11544

Background: Fertility loss is a main side effect of adjuvant CT in young women with BC. AMH was evaluated as a potential marker of residual ovarian function after CT. Method: AMH (ng/mL), FSH (mIU/mL), E2 (pg/mL) and menstrual activity were evaluated before CT and every 3 months after CT in pre-menopausal BC patients ( pts ) enrolled in a phase III study evaluating the role of triptorelin in the prevention of CT-induced early menopause. Means were compared with Student t test for paired data, anova or ancova. The effect of age, CT regimen, FSH and AMH on time to menstrual resumption was investigated by means of the Cox's proportional hazards model. Results: Among 26 evaluable pts at baseline, mean age was 39 years (range 27-45). Baseline mean values were: FSH 5.67 (SD 4.88), E2 151.81 (SD 134.9), AMH 2.67 (SD 1.85). Levels of AMH were significantly lower (1.26) in old pts ( ≥ 41 yrs) as compared to younger ones (2.97 and 3.63 in 25–36 yrs and 37–40 yrs old women, respectively) (p=0.018). After CT, mean value of AMH significantly decreased from 2.04 ( SD 1.44 ) to 0.59 ( SD 0.59 ) (p=0.0003 ); FSH value increased, from of 8.64 (SD 12.99) to 23.13 (SD 25.80) (p=0.017) and E2 values decreased from 159.71 (SD 147.03) to 73.29 (SD 129.53) (p=0.02). The mean decrease of AMH levels was not affected by the type of CT regimens: -1.50, -1.52 and -1.33 after FEC ⋄ Paclitaxel, FEC ⋄ Taxotere and FEC/CMF, respectively (p=0.97). Among 10 pts with both early (0–5 months) and delayed (6–11 months) post-CT evaluations, no change in AMH values was observed with longer follow up: mean values were 1.49, 0.35 and 0.36, at baseline, after 0–5 months and after 6–11 months, respectively. Menstrual activity resumption occurred in 48% of patients. At multivariate analysis factors significantly associated with the lower probability of menstrual activity resumption after CT were: old age (p=0.05) and chemotherapy with FEC ⋄ docetaxel ( p=0.05 ). In this preliminary analysis baseline and after CT values of AMH were not significantly associated with menstrual resumption. Conclusions: Adjuvant CT significantly affects the levels of AMH in young women with BC. Further studies are needed to assess the role of AMH as a surrogate of ovarian toxicity induced by CT.

No significant financial relationships to disclose.
Uptake by breast carcinoma of a lipidic nanoemulsion after intralesional injection into the patients: A new strategy for neoadjuvant chemotherapy
Authors: Graziani S. , Mendes S. , Vitório T. S. , Padoveze A. F. , Hegg R. , Bydlowski S. P. , Maranhão R. C.
Published: August 2020

e11555

Background: Previously we showed that after intravenous injection a lipidic nanoemulsion concentrates in breast carcinoma tissue and other solid tumors may carry drugs directed against neoplastic tissues. Use of the nanoemulsion decreases toxicity of the chemotherapeutic agents without decreasing the anticancer action. Currently, the hypothesis was tested whether the nanoemulsion concentrates in breast carcinoma tissue after locoregional injection. Methods: Three different techniques of injection of the nanoemulsion were tested in patients scheduled for surgical treatment: G1 (n=4) into the mammary tissue 5 cm away from the tumor; G2 (n=4) into the peritumoral mammary tissue; G3 (n=6) into the tumoral tissue. The nanoemulsion labeled with radioactive cholesteryl oleate was injected 12 hours before surgery; plasma decay of the label was determined from blood samples collected over 24 h and the tissue fragments excised during the surgery were analyzed for radioactivity uptake. Results: Among the three nanoemulsion injection techniques, G3 showed the greatest uptake (data expressed in c.p.m/g of tissue) by the tumor (44769±54749) and by the lymph node (2356±2966), as well as the greatest concentration in tumor compared to normal tissue (844±1673). In G1 and G2, uptakes were, respectively, tumor: 60±71 and 843±1526; lymph node: 263±375 and 102±74; normal tissue: 139±102 and 217±413. Conclusions: Therefore, with intralesional injection of the nanoemulsion, a great concentration effect can be achieved. This injection technique may be thus a promising approach for drug-targeting in neoadjuvant chemotherapy in breast cancer treatment.

No significant financial relationships to disclose.
Retrospective comparison of response rates and survival with neoadjuvant docetaxel versus anthracycline-based chemotherapy for locally advanced breast cancer patients
Authors: Gupta D. , Raina V. , Shukla N. K. , Rath G. K. , Mohanti B. K. , Sharma D. N.
Published: August 2020

e11564

Background: LABC is a major problem in our country comprising of ≥ 20% of all breast cancer patients. Neoadjuvant chemotherapy is now standard treatment for LABC but randomized trials have failed to show survival advantage. Methods: We retrospectively analyzed locally advanced breast cancer (stage III) patients who received neoadjuvant chemotherapy (NACT) from January 2000 to December 2008. Out of 3000 case records screened, 570 (19%) were LABC and 110/570 (19%) treatment-naïve patients started on NACT were analyzed. Ninety one (37 docetaxel [D], 54 anthracycline [A]) patients were eligible for response and survival analysis. Pathological CR (pCR) was defined as no evidence of malignancy in both breast and axilla. Survival curves generated using Kaplan-Meier method and survivals compared using log-rank test. Results: Median age of whole cohort was 45 years (range 25–68 years). Premenopausal were 42% and ER+ 49.5%. Most (90%) were T4 tumors and 70% were stage IIIB. Median number of preoperative cycles was 3 and 6 in D and A group. Overall clinical response rates for breast primary were 74.3% (CR 28.6%) and 53.7% (CR 16.7%, p=0.58) while for axilla ORR were 75.7% (51.4% CR) vs 54.8% (40.4% CR, p=0.77) respectively for D and A. Corresponding pCR rates were 19% vs 13% respectively. There was no significant difference in disease free (3 year 56.84% vs 61.16%, p=0.80) and overall survival (3 year 70% vs 78.5%, p=0.86) between two groups. Those who achieved pCR in both groups also had no survival advantage (p=0.34) over non achievers. There was no difference in pCR rates for ER+ vs ER- patients but ER+ patients had significantly higher DFS than ER- patients (p=0.05). Conclusions: Although pCR rates were higher with docetaxel based NACT, it did not translate into superior DFS/OS compared to anthracycline based chemotherapies. Achievement of pCR too, was not associated with any survival advantage.

No significant financial relationships to disclose.
Safety and effectiveness of dose dense neoadjuvant chemotherapy in patients with stage II/III breast cancer
Authors: Koya S. , Li Y. , McDaniel S. A. , LoBuglio A. F. , Krontiras H. , Carpenter J. , Nabell L. , Bland K. , Falkson C. , Forero A.
Published: August 2020

e11566

Background: NSABP B-18 randomized women with operable breast cancer to receive chemotherapy (AC) either pre- or postoperatively; in the study there was no significant difference in disease free survival (DFS) or overall survival (OS) among patients in either group. Pathologic complete response rate (pCR) was directly proportional to DFS and OS. Dose dense adjuvant chemotherapy (ATC) has shown a statistically significant improvement in DFS and OS. Methods: We performed a single institution review of pts enrolled in a neoadjuvant trial and who received dose dense neoadjuvant chemotherapy (doxorubicin 60 mg/m2 IV Q2wks x4, paclitaxel 175 mg/m2 IV Q2wks x4, and cyclophosphamide 600 mg/m2 IV Q2wks x4) to assess response rates, safety, and DFS. Women with newly diagnosed breast cancer, T ≥ 3cm, any N, M0 were enrolled. Results: Since 02/2003, 43 pts were enrolled (mean age 47.6, range 28–64) and received dose dense chemotherapy. 41.4% of the pts were triple negative and 14.6% were Her2+ by FISH or IHC. The median follow-up is 49 months (range 8–69). Two patients dropped out without finishing therapy. Forty one pts completed dose dense chemotherapy and proceeded to surgery. 17 pts (41.4%) achieved a pCR in the breast and of those 14 pts were also negative in the axillary lymph nodes (34.1% pCR in the breast and lymph nodes). 10 of the 17 pts with pCR in the breast (8 out of the 14 pts with pCR in breast and axillary lymph nodes) were triple negative. 18 pts (43.9%) achieved PR, 3 pts (7.31%) had SD and 3 pts (7.31%) had PD. Up to November 2008, 7 pts who did not have a pCR have relapsed (4 triple negative, 1 Her2+, 1 ER/PR positive and 1 ER negative, PR positive) with a relapsed free survival rate of 85%. Hematologic toxicity consisted of grade 3 anemia in 2 patients with no grade 4 anemia, no G4 thrombocytopenia and febrile neutropenia in 2 pts. Non-hematologic grade 3 or 4 toxicity consisted of mediport thrombosis in 2 pts, hyperglycemia in 2 pts, syncope in 1 pt, neuropathy in 1 pt, and varicella zoster in 1 pt. Conclusions: Our results show that dose dense neoadjuvant chemotherapy achieves a pCR (breast + node) in about 1/3 of patients (34%) with tolerable toxicity; although the number of patients is limited, our data suggest that triple negative breast cancer seems to be the most sensitive tumor to this regimen.

No significant financial relationships to disclose.
Video-assisted skin-sparing breast-conserving surgery for breast cancer and immediate reconstruction with autologous tissue: Clinical outcomes
Authors: Fujiwara I. , Nakajima H. , Mizuta N. , Sakaguchi K. , Hachimine Y.
Published: August 2020

e11580

Background: This study analyzed clinical results of video-assisted breast-conserving surgery for breast cancer. Methods: Video-assisted breast-conserving surgery is indicated for breast cancer that has not invaded the skin. A skin incision is made at an inconspicuous site. Skin-sparing partial mastectomy was performed endoscopically on 244 patients (stage I, n=94; stage II, n=150). Morbidity, curability and patient satisfaction were analyzed. Results: Skin necrosis was seen in 9 patients. Local recurrence was seen in 13 patients (mean postoperative interval, 65.3 months). Distant metastasis-free survival at 60 months was 93.6% for stage I and 90.5% for stage II. Overall survival was 95.7% for stage I and 96.9% for stage II. Satisfaction with surgery as investigated by questionnaire was “good” for 72.3% of patients. Conclusions: Video-assisted breast-conserving surgery showed no increases in local or distant recurrence and patient satisfaction was high. Video-assisted breast-conserving surgery appears useful for local treatment of breast cancer.

No significant financial relationships to disclose.
Same-day breast core biopsy result: Effect on ER/PR and HER-2 scores
Authors: Al-Sam S. , Al-Ramadhani S. , Jader S. , Singer J. , Aylwin A.
Published: August 2020

e11585

Background: The peloris rapid tissue processor promises same-day biopsy results. It uses a unique ActivFlo system achieving fast processing by rapid even heating and reagent exchange. The effect on ER/PR, Her2 scores and morphology of tumour cells are assessed Methods: 80 breast core biopsies were so far included in this study. For each case, one of three core biopsies was processed by the Peloris and the other two by the Leica histology processor for next day reporting. Each core biopsy was fixed in formalin for at least 3 - 6 hours before being processed by both systems.Immunohistochemistry for ER, PR and Her2 was carried out as well as FISH for borderline Her2 cases scoring 2+. Microscopical features were compared by the same histopathologist and tumour grade and type were recorded Results: On comparing cases processed by Peloris and Leica, 47 out of 68 biopsies (69%) scored exactly the same for ER and PR. 16 biopsies (23.5%) had minor scoring differences but did not affect the overall hormone receptor status. In total, 63 out of 68 biopsies (94%) scored similar receptor status. 4 cases (6%) had differing ER/PR status. 56 cases had Her2 tested, 51 (91%) had similar scores and 5 (9%) had different scores. 14 borderline cases had FISH tests and no different results were seen between Peloris and Leica processed tissue. Morphologically there were differences in size of nuclei and nuclear chromatin appearances. We have started the second part of the study in which biopsies for the Peloris are loaded immediately on receipt giving about 30 minutes of formalin fixation. Of the 9 biopsies so far processed, there have been no noticeable differences between the fixed tissue on the Leica processor and the fresh tissue on Peloris with regards to ER, PR and Her2. Conclusions: In conclusion, immunohistochemistry for ER/PR and Her2 is similar in 93% and 91% cases respectively. Results for FISH test were similar in all 14 cases. However, morphological differences were noted and the effect on tumour grade was discussed. Further evaluation and comparison of tissue using both processors on morphological architecture need to be carried out and any differences reported.

No significant financial relationships to disclose.
Gene Expression and RNA Splicing Imputation Identifies Novel Candidate Genes Associated with Osteoporosis
Authors: Liu Yong , Shen Hui , Greenbaum Jonathan , Liu Anqi , Su Kuan-Jui , Zhang Li-Shu , Zhang Lei , Tian Qing , Hu Hong-Gang , He Jin-Sheng , Deng Hong-Wen
Published: August 2020

Context

Though genome-wide association studies (GWASs) have identified hundreds of genetic variants associated with osteoporosis related traits, such as bone mineral density (BMD) and fracture, it remains a challenge to interpret their biological functions and underlying biological mechanisms.

Objective

Integrate diverse expression quantitative trait loci and splicing quantitative trait loci data with several powerful GWAS datasets to identify novel candidate genes associated with osteoporosis.

Design, Setting, and Participants

Here, we conducted a transcriptome-wide association study (TWAS) for total body BMD (TB-BMD) (n = 66 628 for discovery and 7697 for validation) and fracture (53 184 fracture cases and 373 611 controls for discovery and 37 857 cases and 227 116 controls for validation), respectively. We also conducted multi-SNP-based summarized mendelian randomization analysis to further validate our findings.

Results

In total, we detected 88 genes significantly associated with TB-BMD or fracture through expression or ribonucleic acid splicing. Summarized mendelian randomization analysis revealed that 78 of the significant genes may have potential causal effects on TB-BMD or fracture in at least 1 specific tissue. Among them, 64 genes have been reported in previous GWASs or TWASs for osteoporosis, such as ING3, CPED1, and WNT16, as well as 14 novel genes, such as DBF4B, GRN, TMUB2, and UNC93B1.

Conclusions

Overall, our findings provide novel insights into the pathogenesis mechanisms of osteoporosis and highlight the power of a TWAS to identify and prioritize potential causal genes.
Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) in Patients With Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis
Authors: de Vries Marieke , Westerink Jan , Kaasjager Karin H A H , de Valk Harold W
Published: August 2020

Context

Nonalcoholic fatty liver disease (NAFLD) prevalence is high, especially in patients with obesity and type 2 diabetes, and is expected to rise steeply in the coming decades.

Objective

We estimated NAFLD prevalence in patients with type 1 diabetes and explored associated characteristics and outcomes.

Data Sources

We reviewed PubMed and Embase for studies on NAFLD and type 1 diabetes to March 2020. We screened references of included articles.

Study Selection

Two authors independently screened titles/abstracts. One author screened full text articles. NAFLD was defined as described in the individual studies: steatosis and/or fibrosis. Studies not reporting alternative causes of hepatic steatosis or defining NAFLD only as elevated liver enzymes, were excluded. Initially, 919 articles met the selection criteria.

Data Extraction

One researcher performed data extraction and risk of bias assessment using standardized tables.

Data Synthesis

We assessed pooled prevalence rates by meta-analysis using a random-effects model, subsequently exploring heterogeneity by subgroup-, meta-regression-, and sensitivity analysis. Twenty studies between 2009 and 2019 were included (n = 3901). Pooled NAFLD prevalence was 19.3% (95% CI, 12.3%-27.5%), increasing to 22.0% (95% CI, 13.9%-31.2%) in adults only. Pooled prevalence of ultrasound studies was high (27.1%, 95% CI, 18.7%-36.3%) compared to studies using magnetic resonance imaging (8.6%, 95% CI, 2.1%-18.6%), liver biopsy (19.3%, 95% CI, 10.0%-30.7%), or transient elastography (2.3%, 95% CI, 0.6%-4.8%).

Conclusion

NAFLD prevalence in patients with type 1 diabetes is considerable and is highly dependent on the specific diagnostic modality and NAFLD definition used. These data are helpful in directing actions to standardize NAFLD diagnosis, which will help defining contributing mechanisms and outcomes.