tbuckley/cabot-search huggingface dataset:
Clinicopathologic analysis of low grade appendiceal mucinous neoplasm
Authors: Xiumin Qi, Ping Sun
Journal: BMJ (2016)

The clinicohistological features of 12 patients with low grade appendiceal mucinous neoplasm admitted from July 2011 to July 2015 were retrospectively analyzed. Ten patients complained lower abdominal pain, 5 cases presented space occupying lesions or abscess in appendix with ultrasound or CT examination, 2 cases presented cystic space occupying lesions in ileocecus on medical examination. The patients were generally characterized by enlargement of appendix, and cystic formation filled with jelly material. Histopathology showed appendix cavity expansion, lining single-layer mucus columnar epithelium with mild atypia and local papillary hyperpasia; appendix cavity partly bursted, and a large amount of mucus filled with appendix wall. Calcifications were found in 6 cases, floating broken epithelioid cells in 2 cases, calcified schistosome eggs in 2 cases. It is significant to understand the clinical and pathological features of LAMN.


Key words: 
Appendiceal neoplasms; Mucus; Clinicopathologic features
Should governments continue lockdown to slow the spread of covid-19?
Authors: Edward R Melnick, John P A Ioannidis
Journal: BMJ (2020)

Until we have a meaningful alternative, lockdown is the only thing we can do to prevent further catastrophic spread of the virus, says <b>Edward R Melnick</b>. But <b>John PA Ioannidis</b> argues that any benefits of lockdown depend on its effectiveness and the covid-19 burden—and that the harms are multifarious
2型糖尿病勃起功能障碍全身治疗和局部治疗的比较
Authors: 毕会民, 张杰, 张孝斌, 胡胜, 甘佩珍
Journal: BMJ (2004)

将105名2型糖尿病勃起功能障碍患者随机分为三组,分别给予一般血糖控制治疗,阴茎海绵体前列腺素E1注射局部治疗,甲钴胺、西洛他唑和十一酸睾酮口服全身治疗.采用单盲、对照的方法进行临床试验,比较全身给药与局部治疗对糖尿病勃起功能障碍的安全性及有效率。
Risk factors and chronic complications of type 2 diabetes with fatty liver
Authors: Jun-li Wang
Journal: BMJ (2012)

Clinical data of 365 patients with type 2 diabetes admitted from December 2010 to May 2011 were retrospectively analyzed,including 130 cases with fatty liver and 235 non-fatty liver cases.There were no differences in gender,age,disease course between two groups (P ＞ 0.05). BMI,glycated hemoglobin (HbAlc),blood pressure,TC,TG,LDL-C,large vessels complications and microvascular complications rate in fatty liver group were significantly higher than those in non-fatty liver group ( all P ＜0.01 ),while there was no difference in rate of peripheral neuropathy (P ＞ 0.05 ).The results indicate that blood glucose,blood pressure,BMI,abnormal blood lipid and chronic complications were closely related to type 2 diabetics with fatty liver.

Key words: 
Diabetes, type 2; Fatty liver
Phosphoinositide 3-Kinase–Regulated Pericyte Maturation Governs Vascular Remodeling
Authors: Ana M. Figueiredo, Pilar Villacampa, Rodrigo Diéguez-Hurtado, Juan José Lozano, Piotr Kobialka, Ana Rosa Cortazar, Anabel Martinez-Romero, Ana Angulo-Urarte, Claudio A. Franco, Marc Claret, Ana María Aransay, Ralf H. Adams, Arkaitz Carracedo, Mariona Graupera
Journal: Circulation (2020)

Pericytes regulate vessel stabilization and function, and their loss is associated with diseases such as diabetic retinopathy or cancer. Despite their physiological importance, pericyte function and molecular regulation during angiogenesis remain poorly understood.To decipher the transcriptomic programs of pericytes during angiogenesis, we crossed Pdgfrb(BAC)-CreERT2 mice into RiboTagflox/flox mice. Pericyte morphological changes were assessed in mural cell-specific R26-mTmG reporter mice, in which low doses of tamoxifen allowed labeling of single-cell pericytes at high resolution. To study the role of phosphoinositide 3-kinase (PI3K) signaling in pericyte biology during angiogenesis, we used genetic mouse models that allow selective inactivation of PI3Kα and PI3Kβ isoforms and their negative regulator phosphate and tensin homolog deleted on chromosome 10 (PTEN) in mural cells.At the onset of angiogenesis, pericytes exhibit molecular traits of cell proliferation and activated PI3K signaling, whereas during vascular remodeling, pericytes upregulate genes involved in mature pericyte cell function, together with a remarkable decrease in PI3K signaling. Immature pericytes showed stellate shape and high proliferation, and mature pericytes were quiescent and elongated. Unexpectedly, we demonstrate that PI3Kβ, but not PI3Kα, regulates pericyte proliferation and maturation during vessel formation. Genetic PI3Kβ inactivation in pericytes triggered early pericyte maturation. Conversely, unleashing PI3K signaling by means of PTEN deletion delayed pericyte maturation. Pericyte maturation was necessary to undergo vessel remodeling during angiogenesis.Our results identify new molecular and morphological traits associated with pericyte maturation and uncover PI3Kβ activity as a checkpoint to ensure appropriate vessel formation. In turn, our results may open new therapeutic opportunities to regulate angiogenesis in pathological processes through the manipulation of pericyte PI3Kβ activity.
Hormonal rehabilitation in patients with endothelial and cervical cancers.
Authors: Natalia V. Chernikova, Tatiana I. Moiseenko, Alla I. Shikhlyarova, Ekaterina V. Verenikina, Yuriy A. Poryvaev, Tatiana Yu. Myagkova, Polina A. Kruze, Oksana E. Zhenilo, Anna A. Cherkasova, Tatiana G. Chalabova, Oleg I. Kit
Journal: Journal of Clinical Oncology (2020)

e18025 Background: Young patients with early stages of gynecological cancers often go through surgical menopause which worsens the quality of life affecting social, sexual, psycho-emotional, cognitive spheres, and causes somatic diseases rare in a young age. The purpose of the study was to evaluate the clinical effectiveness of medical and hormone replacement therapy (HRT) in patients with endothelial (EC) and cervical cancers (CC) of the reproductive age after surgical treatment. Methods: Clinical data and adaptive reactions were studied in 346 patients with stage Ia-IIa EC and CC aged 20-45 years after combination treatment. Patients were divided into 3 groups: group 1 – 192 patients, estrogen/gestagen HRT; group 2 – 112 patients, treatment with phytoestrogens; group 3 – 42 patients choosing not to have any adjuvant therapy. The Kupperman index was used to evaluate the severity of a post-castration syndrome. Results: In group 1, 158 women (82.3%) showed normal somatic and psychoemotional status and adequate cognitive functions, the Kupperman index ≤20; 34 (17.7%) patients of group 1 needed additional sedation, the Kupperman index = 30; adaptive reactions included reactions of training and adaptation. In group 2, 112 patients (100%) demonstrated moderate hormonal imbalance signs: vegetative and emotional disorders, decreased libido, manifestations of the metabolic syndrome, the Kupperman index = 30-35; adaptive reactions included reactions of training and stress. All patients of group 3 (n = 42) developed metabolic disorders shortly after surgical castration, with social, sexual and psycho-emotional disadaptation, the Kupperman index = 35 (reactions of stress). Conclusions: Combination HRT after surgical castration contributes to full adaptation in the social, sexual, psycho-emotional spheres of life in patients of the reproductive age, restoring the quality of life without affecting the prognosis.
Posttranslational modifications define course of prion strain adaptation and disease phenotype
Authors: Natallia Makarava, Jennifer Chen-Yu Chang, Kara Molesworth, Ilia V. Baskakov
Journal: Journal of Clinical Investigation (2020)

Posttranslational modifications are a common feature of proteins associated with neurodegenerative diseases including prion protein (PrPC), tau, and α-synuclein. Alternative self-propagating protein states or strains give rise to different disease phenotypes and display strain-specific subsets of posttranslational modifications. The relationships between strain-specific structure, posttranslational modifications, and disease phenotype are poorly understood. We previously reported that among hundreds of PrPC sialoglycoforms expressed by a cell, individual prion strains recruited PrPC molecules selectively, according to the sialylation status of their N-linked glycans. Here we report that transmission of a prion strain to a new host is accompanied by a dramatic shift in the selectivity of recruitment of PrPC sialoglycoforms, giving rise to a self-propagating scrapie isoform (PrPSc) with a unique sialoglycoform signature and disease phenotype. The newly emerged strain has the shortest incubation time to disease and is characterized by colocalization of PrPSc with microglia and a very profound proinflammatory response, features that are linked to a unique sialoglycoform composition of PrPSc. The current work provides experimental support for the hypothesis that strain-specific patterns of PrPSc sialoglycoforms formed as a result of selective recruitment dictate strain-specific disease phenotypes. This work suggests a causative relationship between a strain-specific structure, posttranslational modifications, and disease phenotype.
4-gene score to predict response to neoadjuvant chemotherapy, metastasis, and survival.
Authors: Masanori Oshi, Eriko Katsuta, Li Yan, Itaru Endo, Kazuaki Takabe
Journal: Journal of Clinical Oncology (2020)

e12592 Background: At this point, there is no treatment to cure metastatic breast cancer. On the other hand, improvement of treatment of metastatic breast cancer is the key to further improve breast cancer survival. One possible opportunity is to detect metastatic breast cancer in it’s “early” phase when it many respond to treat such as immune therapy. We hypothesized that a scoring system generated from metastatic clone predict metastasis and survival. Methods: A gene signature score was generated using differentially expressed genes between MDA-MB-231 human breast cancer cell-line and its highly metastatic variant, LM2-4, and TCGA breast cancer dataset. METABRIC cohort as well as six neoadjuvant therapeutic cohorts and four metastatic cohorts were used as validation cohort. The totals of 4,199 samples from a large number of cohorts were analyzed in the study. Results: Among the 297 genes that were up-regulated in LM2-4, tumor expression of four genes had the strongest association with disease-free survival in TCGA breast cancer dataset (hazard ratio [HR] &gt; 1.2 with p &lt; 0.02). A 4-gene score calculated from the combined expression of these genes correlated with overall survival in TCGA data, with HR of 1.44 (95% confidence interval [CI] = 1.52-2.98; p &lt; 0.001). The association of higher scores with worse survival was also observed for disease-specific survival in the METABRIC breast cancer cohort (HR = 1.57, 95% CI = 1.23-1.72, p &lt; 0.001). Tumors with high score enriched gene sets related with cancer aggressiveness such as E2F, G2F, MYC v1 and v2 (FDR = 0.23, 0.19, 0.20, 0.21, respectively), whereas those with lower score enriched estrogen response pathway related set (FDR = 0.13) in TCGA and it was validated with METABRIC cohorts. We also found that the score associated with distant metastasis to brain or lung (p &lt; 0.001). Kaplan-Meier analyses of site-specific metastasis-free interval demonstrated that for all three cohorts, patients with high scores had significantly increased risk for development of metastasis to the lung (p≤0.02). This association of the score with metastasis risk was also seen for brain for two cohorts, and it was seen for bone in one cohort. Importantly, we found that the high score group had a higher pCR rate than the low score group for especially ER+/HER2- breast cancer in two cohorts (p = 0.003 and p = 0.004). And the score significantly decreases with good response to neoadjuvant chemotherapy (p = 0.022) or hormonal therapy (p = 0.013). Conclusions: This novel gene score may be clinically useful with both prognostic and predictive values for breast cancer.
Clinicopathological correlation of serum vascular endothelial growth factor and tissue carbonic anhydrase factor IX in stage IA to IIA carcinoma cervix.
Authors: Shalini Rajaram, Musarrat Bahadur Khan, Bindiya Gupta, Vinod Kumar Arora, Rafat Ahmed, Lalendra Upreti
Journal: Journal of Clinical Oncology (2020)

e18012 Background: VEGF initiates endothelial cell proliferation and angiogenesis in tumour cells while CA IX has an important role in pH regulation and elimination of hypoxia generated acid load during glycolysis.The present study was designed to identify these biomarkers and their correlation with tissue spread and behavior and eventually could lead to development of novel target therapies. The objective of this study was to correlate serum VEGF levels and tissue CA IX expression with clinicopathological features of carcinoma cervix stage IA to IIA. Methods: This exploratory case-control study included 19 cases with carcinoma cervix FIGO 2009 stage IA to IIA and 19 age matched controls. Out of the 19 cases, 12 underwent surgery and 7 received chemoradiation. Pre-therapy blood samples were collected for serum VEGF estimation from both cases and controls. For CA IX expression estimation, cervical tissue was taken for analysis. For cases, post-operative / post chemoradiation blood samples were taken for VEGF level estimation after 6 weeks. Results: The difference in mean serum VEGF levels between cases 1235.84 pg/ml (SD± 433.67) and controls 153.74 pg/ml (SD± 108.11) was statistically significant (p = 0.001). Mean serum VEGF level between pre and post-operative cases was 1108 pg/ml (SD± 407.62) and 391.42 pg/ml (SD± 270.71) while in pre and post chemoradiation cases it was 1455 pg/ml (SD± 413.38) and 623 pg/ml (SD± 238.41). This decrease was statistically significant (p = 0.00 &amp; p = 0.018). VEGF positively correlated with histopathologic type (p = 0.016), grade (p = 0.012), and lymphovascular space invasion (p = 0.042).CA IX expression was seen in all cases while in controls no expression was seen. CA IX expression had a positive association with lymphnode metastasis (p = 0.041). Conclusions: Elevated pre-therapeutic serum VEGF suggests spread of tumor and can be used as a prognostic marker for cancer cervix. CA IX immunostaining in cervical biopsy samples can be used as a surrogate marker for tumor aggressiveness and distant spread.
The incidence and impact of brain metastasis in patients with hereditary <i>BRCA1/2</i> mutated invasive breast cancer in a prospectively followed cohort.
Authors: Haven Garber, Michael Lehner, Akshara Singareeka Raghavendra, Angelica M. Gutierrez-Barrera, Debu Tripathy, Jennifer Keating Litton, Banu Arun, Nuhad K. Ibrahim
Journal: Journal of Clinical Oncology (2020)

1096 Background: Previous reports suggest the incidence of brain metastasis is higher in patients with hereditary BRCA1 mutations compared to BRCA1 noncarriers among breast cancer patients who develop recurrent disease. PARP inhibitors are now standard therapies for metastatic breast cancer patients with germline BRCA1 or BRCA2 mutations ( gBRCA1/2) based on their efficacy in treating systemic disease. However, as management of systemic disease improves, a concern is that patients with hereditary BRCA mutations may experience higher rates of disease progression in the CNS. We aimed to estimate the incidence of brain metastasis in breast cancer patients with gBRCA1/2 using a prospectively maintained gBRCA database and to assess the impact of brain metastasis on survival. Methods: To determine incidence, we queried a prospectively maintained electronic database that included patients referred to the MDACC genetics department and who underwent gBRCA1/2 testing. We identified patients with stage I-III invasive breast cancer who were treated between 2000-2017 and assessed for disease recurrence and brain metastasis. To expand our cohort for descriptive characteristics (separate from the incidence analysis), we queried the Breast Medical Oncology database for patients with brain metastasis who had undergone BRCA1/2 testing outside the genetics department or at outside institutions. Results: Of 474 patients with Stage I-III breast cancer and gBRCA1, 77 (16.2%) developed distant metastasis (median f/u: 9.1 years). Of these patients, 34/77 (44.2%) developed brain metastasis. In comparison, 42 of 318 (13.2%) of gBRCA2 patients with Stage I-III breast cancer developed distant recurrence (median f/u: 8.4 years), and 7/42 (16.7%) experienced brain metastasis. In gBRCA1 patients with brain metastasis, 45/48 (83.8%) had triple negative disease, and the median time from diagnosis to brain metastasis was 2.45 years. The brain was among the initial sites of disease recurrence in 24/48 (50%) of gBRCA1 patients. For gBRCA1 patients with distantly recurrent disease, median OS from diagnosis was 3.19 years for patients with brain metastasis vs. 5.37 years for patients without brain mets (HR 0.54; 95% CI 0.34 to 0.85; P = 0.0082). Conclusions: Brain metastasis is frequent among breast cancer patients with recurrent disease and hereditary BRCA1 mutations. Development and testing of agents with intracranial activity is critical for improving long-term outcomes in gBRCA1 patients with metastatic breast cancer.
Omission of adjuvant chemotherapy in elderly patients with early stage breast cancer.
Authors: Sung Jun Ma, Oluwadamilola Temilade Oladeru, Anurag K Singh
Journal: Journal of Clinical Oncology (2020)

12032 Background: Breast cancer incidence in elderly population over 70 years is anticipated to grow up to 35% by 2030. However, this elderly population is under-represented in the TAILORx (Trial Assigning Individualized Options for Treatment) with less than 5% of the entire study cohort. As the omission of radiation therapy among the elderly with favorable prognosis is a reasonable alternative option, omission of chemotherapy has not been prospectively investigated. To address this knowledge gap, we conducted an observational cohort study to evaluate the omission of chemotherapy in elderly patients with early breast cancer. Methods: The National Cancer Database (NCDB) was queried for patients above the age of 70 diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1-2N0 breast cancer who underwent hormone therapy with or without chemotherapy (2010-2015). Kaplan-Meier method and Cox multivariable analysis (MVA) were performed for survival analysis. Propensity score matching in a 1:1 ratio without any replacement was used to address selection bias. Sensitivity analysis was performed on a subgroup of those with a high 21-gene recurrence score (RS) &gt; 25. Results: A total of 12004 patients were identified, including 10802 and 1202 patients with and without adjuvant chemotherapy, respectively. The median follow up was 38.2 months (IQR 22.5-57.2). On univariate analysis, chemotherapy was not associated with improved overall survival (HR 0.96, p = 0.71), ineligible for inclusion in the final MVA model. On interaction analysis, the use of chemotherapy had no interaction with RS (p = 0.46), age (p = 0.08), tumor size (p = 0.23), tumor grade (p = 0.42), and comorbidity score (p = 0.22). On 1030 and 689 matched pairs for all RS and RS &gt; 25, respectively, there was no association of overall survival with chemotherapy (all RS: HR 0.76, p = 0.08; RS &gt; 25: HR 0.74, p = 0.10). Conclusions: For elderly patients with early stage breast cancer, the addition of adjuvant chemotherapy may not be associated with improved survival even in the setting of high RS &gt; 25. Given the toxicity profile of systemic therapy, shared decision making between clinicians and elderly patients is needed to individualize treatment options.
Comparison of the predictive power of survival of the Royal Marsden Score (RMS), the Gustave Rousy Immunescore (GRIM score), the MDACC score (MDAS) and the LIPI score in phase I trials patients.
Authors: Eduardo Castanon Alvarez, Leyre Resano, Luis Barba, Covadonga Vidal, Alvaro Sanchez Arraez, Antonio Gonzalez Martin, Mariano Ponz-Sarvisé
Journal: Journal of Clinical Oncology (2020)

e14094 Background: Selection of patients for enrolment in phase I trials is critical. Initial scores (RMS or MDAS) were designed to select patients with higher probability to obtain benefit in a clinical trial, followed by others such as GRIM score and the LIPI score. In this study, we have performed a comparison of the four scores in order to detect the most optimal one to select patients for immunotherapy phase I trials. Methods: We retrospectively studied 248 patients who participated in immunotherapy phase I trials in our institution from 2012-2019. We calculated high or low risk for each patient according to punctuation in RMS (number of metastasis,LDH, albumin), GRIM score (LDH, Albumin, NLR &gt; 6), MDAS (RMS, ECOG &gt; = 1, gastrointestinal tumors) and LIPI score (LDH, NLR &gt; 3) at the time of screening. Overall survival (OS) was defined as the time between first dose and date of death or lost to follow up. Cox regression model was performed for predicting OS. C-Harrell index and its confidence interval were calculated for each score for measuring the power of prediction. Differences between c-Harrell indexes were calculated. All calculations were performed with STATA v16.0. Results: In terms of predicting overall survival we found that a higher punctuation in RMS (high vs low HR = 2.14 95% CI 1.47-3.10), Grim score (high vs low HR = 2.14; 95% CI1.51-3.02), MDAS (HR = 1.17 95% CI 1.04-1.31) and LIPI score (high vs low HR = 1.83; 95% CI 1.42-2.37) were all statistically significant. In terms of power of prediction, we found that LIPI score presented a c-Harrel index slightly higher (0.63; 95% CI 0.59-0.68) than GRIM score (0.62; 95% CI 0.57-0.66), MDACC score (0.55 95% CI 0.50-0.62) and RMS (0.62; 95% CI 0.59-0.66). Differences between c-index of each score were not statistically significant. In terms of predicting survival at 90 days, differences between ROC areas for LIPI score (0.64 95% CI 0.56-0.72), Grim Score (0.69 95% CI 0.61-0.76), MDAS (0.57 95% CI 0.48-0.66), and RMS (0.68 95% CI 0.62-0.73) were not statistically significant. Conclusions: Although in this study we have seen a slightly higher predictive power for LIPI score in comparison to GRIM score, MDAS or RMS, differences were not statistically significant. Nevertheless, and assuming the most parsimonious model, LIPI score seemed to be an easy and accurate model for predicting survival. These results might suggest that further prospective analysis are needed to avoid excluding patients based on these scores and who may benefit from phase I trials.