tbuckley/cabot-search huggingface dataset:
Venetoclax-induced tumor lysis syndrome in acute myeloid leukemia: Real world experience.
Authors: Amany Keruakous, Rabia Saleem, Adam Steven Asch
Journal: Journal of Clinical Oncology (2020)

e19542 Background: Venetoclax in combination with hypomethylating agents (HMAs) has become standard management for newly diagnosed older and unfit acute myeloid leukemia (AML) patients and an option for relapsed/refractory disease in cases unfit for aggressive therapy. Although venetoclax can lead to rapid tumor lysis syndrome (TLS) in chronic lymphocytic leukemia and therefore administrated in a weekly dose ramp-up to minimize toxicity, a modified dose ramp-up of venetoclax over 3–4 days in combination with HMAs has been investigated in AML trials without any reported cases of TLS (DiNardo et al, 2019). Notably, this trial prohibited azole fungal prophylaxis because of the known potentiation of venetoclax activity in that setting. Rare cases have been reported for venetoclax induced TLS in the context of CYP3A inhibition. This study presents cases with AML who developed TLS whilst receiving azacitidine/venetoclax combination. Notably, they shared similar pattern of disease progression. Methods: All AML patients who are unfit to receive induction chemotherapy, treated with venetoclax combination either upfront or in the salvage setting starting January 2019 until November 2019 were reviewed retrospectively. TLS was reported using Cairo-Bishop criteria (Cairo &amp; Bishop, 2004), AML risk stratification and response evaluation by ELN-Leukemia NET. Results: We report fourteen cases treated with azacitidine/venetoclax combination, three cases developed venetoclax induced TLS despite following the TLS protocol per the phase 1b trial (administering allopurinol &gt; 72 hours prior to initiation of venetoclax). All cases had intermediate to poor risk AML; all had WBCs &lt; 25 k before starting venetoclax, 2 of 3 patients received CYP3A inhibitors for fungal prophylaxis. Disease burden, defined as per-cent of bone marrow involvement and peripheral circulating blasts, did not increase the risk of TLS. We observed TLS in newly diagnosed (n = 1) and in relapsed AML (n = 2). Also, with first initiation of venetoclax as well as with delayed onset and more prominent with azole fungal prophylaxis. All the cases of venetoclax induced TLS we observed, proved to be refractory to venetoclax combination after resumption of therapy. Conclusions: Venetoclax induced TLS is reportedly rare in AML. In our experience, TLS is more common in real world experience than has been previously reported. More prominent with azole fungal prophylaxis. Additionally, it appears to be associated with disease that proved ultimately refractory to venetoclax combination.
Surgical treatment for acute appendicitis in HIV/AIDS patients
Authors: Yong Zhao, Guo Wei, Yong He, Xin Hua, Hua Wang, Shifeng Feng, Tingyu Chen
Journal: BMJ (2019)

Fifty three HIC/AIDS patients with acute appendicitis treated in our hospital from January 2016 to June 2017 were retrospectively analyzed. The anesthesia and surgery were successfully completed in all patients, and there were no serious intraoperative complications. The postoperative complications occurred in 18 cases (34.0%), including 13 cases (24.5%) of incision infections and 3 cases (5.7%) of lung infections, 1 case of adhesion obstruction (1.9%) and 1 case (1.9%) of new opportunistic infections. All patients were clinically cured after treatment and discharged from the hospital without perioperative death. The characteristics of acute appendicitis in HIV/AIDS patients are emergent onset, poor body condition, lower immunity, more comorbities, rapid condition changes, and high frequency of special infections; the patients with lower CD4 count may have higher postoperative infection, the slower recovery and the poorer outcomes.


Key words: 
HIV infections; Acguired immunodeficiency syndrom; Appendectomy; Appendicitis
A single-arm, prospective, multicenter study on the efficacy and safety of low-dose transdermal fentanyl patch in opioid-naive patients with moderate to severe cancer pain.
Authors: Yong Liu, Qing Li, Yang Yu, Jie Jun Wang, Han Ping Shi
Journal: Journal of Clinical Oncology (2020)

e24149 Background: The efficacy and safety of low-dose fentanyl transdermal patch (TDF) in the treatment of opioid-naive patients with moderate-to-severe cancer pain has no tyet been confirmed. There are little international studies, and none in mainland China. The aim of this study was to explore the effect and tolerability of low dose of TDF in opioid-naive patients with Chinese moderate-to-severe cancer pain, and evaluate the influence on quality of life and cognitive function. Methods: A prospective, single-arm, non-randomized, open-label, multicenter trial was conducted with 285 opioid-naivepatients with moderate-to-severe cancer pain in 14 tertiary hospitals in mainland China. The initial analgesic dose of TDF was 12.5 µg/h, pain assessment (pain score, pain relief and pain response rate) was performed every 3 days for a total of 9 cycles.Adverse reactions and events were monitored over 24 days. In the meantime, quality of life and cognitive function of patient were evaluated with EORTC QLQ-C30 and MMSE. Results: 285 patients with 267(92.00%) completed the trial were enrolled. The average age was 60 (range 28-87) and the average effective therapeutic dose was 6.3±6.08mg.The total pain relief rate was 98.12% (mean pain score ±SD, 5.7±0.89 vs 3.9±1.28; P &lt; 0.001). The efficacy of low-dose TDF on pain relief was consistent in groups separated by gender (p &lt; 0.001), age (p &lt; 0.001), types of cancer (p &lt; 0.001), and baseline pain intensity (p &lt; 0.001). There were 79 patients (29.59%) in the low-dose subgroup, and the pain response rate of the low-dose subgroup was better than other dose groups within one week (p = 0.0018).The adverse effects were mild. The most common adverse reactions are constipation 7.87%, followed by nausea 11.24%, vomiting 4.12%, drowsiness 1.87% and urine retention 1.5%.There was no difference in the incidence of adverse reactions between the low-dose subgroup and the other groups (p &gt; 0.05). Meanwhile, TDF improved the quality of life of patients with moderate-to-severe cancer pain (mean± SD: 46.44±16.96 vs. 67.04±18.02;p &lt; 0.05), without impairing cognitive function(mean ±SD, 29.13±1.54 vs. 28.98±1.99; p &gt; 0.05). Conclusions: Low-dose TDF is effective for opioid-naive patients with moderate-to-severe cancer pain. Adverse reactions are mild and the quality of life of patients is improvedwith little losson cognitive function. Further randomized controlled studies are warranted to investigate the value of low-dose TDF in the treatment of opioid intolerant cancer pain. Clinical trial information: ChiCTR-ONC-17014080 .
本质与表象之间
Authors: 曾昭耆
Journal: BMJ (2007)

一位48岁的女性,因频发咳嗽2个月于3月底来诊.据其称咳嗽为刺激性,偶有少量黏痰,伴喉头发紧、发痒及胸骨后烧灼感,不发热,一般白天较重,平卧及夜眠时咳轻.曾做血常规、胸透、胸部X线片检查,未见异常,OT试验(-)。
Real-world clinical effectiveness and safety of olaparib monotherapy in HER2-negative gBRCA-mutated metastatic breast cancer: Phase IIIb LUCY interim analysis.
Authors: Karen A. Gelmon, Peter A. Fasching, Fergus Couch, Judith Balmana Gelpi, Suzette Delaloge, Intidhar Labidi-Galy, James Bennett, Susan McCutcheon, Sabine Ano, Joyce O'Shaughnessy
Journal: Journal of Clinical Oncology (2020)

1087 Background: OlympiAD (NCT02000622) demonstrated the benefit of olaparib over standard of care in patients (pts) with HER2-negative (HER2-) metastatic breast cancer (MBC) and germline BRCA mutations (gBRCAm). LUCY (NCT03286842) aimed to provide additional data on the real-world effectiveness and safety of olaparib monotherapy in this setting. Methods: This Phase IIIb, open-label, single-arm study of olaparib 300 mg twice-daily, enrolled pts with HER2- gBRCAm MBC who had received a taxane and/or anthracycline in the (neo)adjuvant/metastatic setting, and ≤2 lines of chemotherapy for MBC. Hormone receptor-positive (HR+) pts had progressed on prior endocrine therapy (ET), and further ET was considered unsuitable. Primary endpoint: investigator-defined progression-free survival (PFS). Secondary endpoints: overall survival, time to first subsequent therapy or death (TFST), and investigator-assessed clinical response rate (CRR). The interim analysis was planned after 160 PFS events. Results: From Oct 2018-Sept 2019, 252 pts were enrolled (160 sites, 15 countries; mean age 46.2 [range 22-75] years; 73.4% ECOG PS 0). Median total treatment duration: 7.9 months (mo; range 0.2-20.0). Median PFS: 8.1 mo (95% confidence interval [CI] 6.9, 8.7; 166 events [65.9%]). Clinical trial information: NCT03286842 . Median TFST: 9.7 mo (95% CI 8.7, 11.1). CRR: 48.6% (95% CI 42.2, 55.0). Adverse events (AEs) in &gt;20% of pts (all grades): nausea, anemia, asthenia, vomiting, and fatigue. 24.6% of pts reported a grade ≥3 AE, including anemia (n=33 [13.1%]). 4.4% of pts had an AE leading to treatment discontinuation. Conclusions: Interim results in this real-world population of pts with HER2- gBRCAm MBC were consistent with the OlympiAD study, and support olaparib as a chemotherapy-free alternative treatment for pts with gBRCAm advanced BC. [Table: see text]
Safety and efficacy of checkpoint inhibitors in solid organ transplant recipients with cutaneous squamous cell carcinoma.
Authors: Irene Tsung, Francis P. Worden, Robert J. Fontana
Journal: Journal of Clinical Oncology (2020)

e22014 Background: Immune checkpoint inhibitors (ICI) are increasingly used in solid organ malignancies. However, data are limited regarding their safety and efficacy in solid organ transplant (SOT) recipients at risk for allograft rejection. The aim of this study was to review our experience with ICIs in SOT recipients at a large transplant center. Methods: A retrospective review of ICIs used in SOT recipients from April 2011 to September 2019 was undertaken. Patient clinical and demographic features, ICI regimen, immunosuppression, allograft function, and efficacy were reviewed. Results: There were 8 SOT recipients (3 kidney, 4 liver, 1 lung) with 7 diagnosed with metastatic head and neck (H&amp;N) cutaneous squamous cell carcinoma (cSCC) and 1 with Merkel cell carcinoma. At a median of 150 months [79-219] post-transplant, 6 were treated with cemiplimab and 2 with pembrolizumab after minimizing calcineurin inhibitors (CNI). Overall tumor response was 37.5% at a median of 3.8 months [0-8] of follow-up. However, 3 died of tumor progression and 2 of other causes at a median of 55 days [8-214] after starting ICI. The only irAE reported was severe pneumonitis in one patient requiring intubation and ICI discontinuation but responded to steroids. Two patients received prophylactic steroids and have preserved allograft function and ongoing tumor response at month 6. Conclusions: Our data suggest that minimization of CNI along with judicious use of prophylactic steroids may allow for the safe use of ICIs in SOT recipients with advanced H&amp;N cSCC. Short-term efficacy appears promising and prospective studies are warranted. [Table: see text]
Effectiveness of long-term prescription of hypertensive and diabetic drugs in family doctor contracted service
Authors: Donglei Miao, Jieying Li, Qi Zhao
Journal: BMJ (2017)

Objective
To assess the effectiveness of long-term prescriptions of hypertensive and diabetic drugs in family doctor contracted service.


Methods
A survey on long-term prescription in family doctor contract service was conducted from November 2015 to December 2015 in Shanghai Changning district. Ten center managers, 101 family doctors and 208 contracted patients from 10 community health service centers were surveyed with 3 different types of questionnaires, respectively. The relevant information of long-term prescription, including medication information, health management, contracted service, patient′s acceptance and performance status were collected and assessed.


Results
The 1-month and 2-month prescriptions accounted for 76.5% (156/204) and 13.2% (27/204), respectively. The survey showed that 87.1% (88/101) of family doctors were willing to make long-term prescriptions; 95.6% (195/204) of patients felt convenience of long-term prescription; 88.1% (89/101) of family doctors affirmed that long-term prescriptions effectively reduced the number of re-visits; 93.6% (191/204) of patients thought that long-term prescriptions reduced the visit number and 60.8% (124/204) thought that it reduced medical expenses. The main factors influencing family doctors′ choice of long-term prescription were the stability of disease condition (72.3%, 73/101), the compliance of patients (68.3%, 69/101), the accurate diagnosis (50.5%, 51/101) and long-term regular medication (45.5%, 46/101); 70.6% (144/204) of patients thought that the hypertensive and diabetic drugs included in the long-term prescription catalogue met their needs.


Conclusion
The long-term prescriptions can effectively reduce the re-visits and medical expenses of patients, which is highly recognized and accepted by both family doctors and patients.


Key words: 
Prescription; Chronic disease; Hypertension; Diabetes mellitus
Reconstruction of distal urethra with labia majora fasciocutaneous flap in 9 cases
Authors: Ying-zhai Li, Xue-jun Chen, Shi-feng Nie, Rui-xia Zhao, Sen Ma, San-zhong Wang
Journal: BMJ (2011)

Nine female patients underwent resection of the middle and distal urethra and the urethra was reconstructed with labia majora fasciocutaneous flap.During the operation the bilateral inner side partial flap of labia majora was taken,and penetrated through the tunnel under the labia minora to the urethral incision,then the flap was sutured as tube-shaped and anastomosed with the urethral incision to reconstruct the urethra.Patients were followed-up for up to 11 years,all patients had normal urination,except 1 patient with adenocarcinoma who developed urinary incontinence 1 month after operation and recovered by pelvic floor muscle training.The application of labia majora fasciocutaneous flap is a safe and effective procedure with less trauma and fewer complications in reconstruction of female middle and distal urethra.

Key words: 
Urologic surgical procedures; Urethra
Efficacy and safety of the antibody-drug conjugate (ADC) SAR408701 in patients (pts) with non-squamous non-small cell lung cancer (NSQ NSCLC) expressing carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).
Authors: Anas Gazzah, Charles Ricordel, Sophie Cousin, Byoung Chul Cho, Emiliano Calvo, Tae Min Kim, Carole Helissey, Jin-Soo Kim, Maria Vieito, Valentina Boni, Mustapha Chadjaa, Marie Hospitel, Semra Yoruk, Fabrice Barlesi
Journal: Journal of Clinical Oncology (2020)

9505 Background: We report updated safety and efficacy of DM4-conjugated anti-CEACAM5 ADC from the expansion part of the first-in-human study (NCT02187848; Gazzah A et al. J Clin Oncol. 2019;37:15, 9072) in 92 NSQ NSCLC pts. Methods: CEACAM5 expression was assessed by immunohistochemistry on archived tumor samples. Two cohorts of pts have been analyzed: moderate and high expressors, with CEACAM5 expression at ≥2+ intensity between ≥1% to &lt; 50% and ≥50% of the tumor cell population, respectively. SAR408701 was administered at 100 mg/m 2 IV every 2 weeks. Tumor assessments were done every 4 cycles (8 weeks). Primary endpoint was overall response rate (ORR). Results: As of January 2020, 92 pts were treated: 28 moderate and 64 high expressors, with median age 62.5 years (31–91; 42.4% of pts ≥65), 51.1% male, 71.7% ECOG PS ≥1; median of 3 prior treatments (1–10 lines) for advanced disease, including anti-tubulin agents (60.9%) and anti-PD1/PD-L1 (75%). In the moderate expressor cohort, 2 confirmed partial responses (PR) were observed (ORR 7.1%). In the high expressor cohort, 13 pts had confirmed PRs (ORR 20.3% [95% confidence interval 12.27%–31.71%]); 27 (42.2%) had stable disease; ORR of 17.8% was observed in 45 pts who had prior anti-PD1/PD-L1. Pts had a median of 7 (1–49) cycles; median relative dose intensity was 0.98. Six pts discontinued due to treatment-emergent adverse events (TEAEs). Most frequent TEAEs (all grades) were asthenia (38.0%), keratopathy/keratitis (38.0%), peripheral neuropathy (26.1%), dyspnea (23.9%), and diarrhea (22.8%). 31 pts had dose modification due to a TEAE, including dose reduction for keratopathy/keratitis in 10 pts. Hematological toxicity included leukopenia (14.4%), neutropenia (4.4%), and thrombocytopenia (13.3%). Grade ≥3 TEAEs occurred in 47.8% of pts and were assessed as drug-related in 15.2%. Conclusions: SAR408701 shows promising antitumor activity in heavily pretreated advanced NSQ NSCLC pts with high CEACAM5 expression. SAR408701 was well tolerated, with minimal hematological toxicity compared to conventional chemotherapy; keratopathy was reversible and manageable with dose modification. These data support the activity of SAR408701 in NSQ NSCLC CEACAM5 high expressors. A phase 3 trial evaluating the activity of CEACAM5-DM4 ADC monotherapy in comparison with docetaxel in NSQ NSCLC CEACAM5 high expressors after failure of standard first line chemotherapy and anti-PD1/PD-L1 is underway. Clinical trial information: NCT02187848 .
Survey on knowledge level of atrial fibrillation among general practitioners in Shanghai Pudong New Area
Authors: Lan Ni, Jinhua Xue
Journal: BMJ (2018)

Objective
To survey the knowledge level of atrial fibrillation (AF) among general practitioners (GPs) in Shanghai Pudong New Area.


Methods
From July to September 2016, a stratified cluster sampling method was used to collect questionnaires from GPs who met the inclusion criteria in 12 community health service centers in Shanghai Pudong New Area. A self-made questionnaire was applied according to Current knowledge and management recommendations of atrial fibrillation-2015, which included 5 domains: antithrombotic therapy, rhythm control, ventricular rate control and evaluation of the guideline.


Results
A total of 377 questionnaires were distributed, and 371 were recovered. Among 371 participants there were 151 males and 220 females aged (41.3±8.3) years, including 156 (42.0%) with junior professional titles, 158 (42.6%) with intermediate titles, and 57 (15.4%) with senior titles. More than 90% of participants recognized that age, hypertension, myocardial infarction, and heart valve disease were risk factors of AF. For patient evaluation, 54.2% (201/371) of participants would use electrocardiogram, 47.9% (178/371) would use thyroid function, 21.0% (78/371) would use echocardiography, 3.2% (12/371) would use respiratory sleep monitoring, and 95.4% (354/371) did not heard of cardiovascular implantable electronic devices. 82.2% (305/371) of participants thought rheumatic mitral stenosis, 46.4% (172/371) thought CHA2DS2-VASc score over and 2 and 12.7% (47/371) thought hypertrophic cardiomyopathy as indications for anticoagulant; and 38.5% (143/371) of participants rarely used CHA2DS2-VASc. The rhythm conversion would applied for the onset of atrial fibrillation in 42.9% participants (159/371), for symptoms after the control of ventricular rate in 39.9% (148/371) participants and for symptomatic patients in 12.7% participants (47/371). 59.8% (222/371) of participants did not know the anticoagulation therapy for AF cardioversion, 44.5% (165/371) participants had not heard radiofrequency ablation for AF. 38.5% (143/371) of participants knew the Chinese guidelines for AF, of which 45.5% (65/143) of the GPs used the guidelines; 80.4% (115/143) of the GPs thought the guide was very instructive. GPs with senior professional titles had better mastery of clinical evaluation, antithrombotic therapy, catheter ablation, and awareness of guideline than junior and middle-level general practitioners.


Conclusion
The survey shows that there is relative lack of knowledge on the risk factors, clinical assessment methods, anticoagulation indications and cardioversion anticoagulation therapy of AF, as well as lack of awareness and application of the AF guideline for GPs in Shanghai Pudong New Area.


Key words: 
Atrial fibrillation; Community health centers; General practitioner; Questionnaire survey
急性重度铁灭克农药中毒并发呼吸骤停一例
Authors: 木塔力甫·祖农, 李博
Journal: BMJ (2011)

患者男性,53岁,2008年1月6日,于15:25以自服铁灭克农药3 h、昏迷1 h为主诉急诊收住院.体检体温正常,呼吸16次/min,脉搏90次/min,血压68/29 mm Hg (1 mm Hg=0.133 kPa),昏迷,面色发绀,双瞳等大等圆约0.5 mm、对光反射消失,双肺可闻及散在湿啰音,血糖17.58mmol/L,尿素氮8.3 mmol/L,肌酐152 μmol/L、乳酸脱氢酶234-570 U/L,肌酸激酶373-2888 U/L.诊断:①急性重度铁灭克中毒,②呼吸心跳骤停,③急性肾功能不全,④应激性糖尿病.入院后及时洗胃约10 000 ml,每5分钟阿托品静脉注射液10 mg,连续2次;多巴胺40 mg、间羟胺20 mg静脉滴注.于15:36突然呼吸、心跳停止,瞳孔散大固定,心电图显示直线.立即停止洗胃,行胸外心脏按压、人工辅助呼吸,每5分钟电除颤2次.尼可刹米0.375 g和洛贝林3 mg注射液静脉注射,续予肾上腺素注射液1 mg静脉注射一次,静脉注射硫酸阿托品每5-30分钟10 mg,总量230 mg。
Ancestry-specific gene expression profiles in TNBC tumors.
Authors: Windy Marie Dean-Colomb, Rachel Martini, Akanksha Verma, Jason White, Olivier Elemento, Melissa Davis, Lisa Newman, Upender Manne, Clayton Yates
Journal: Journal of Clinical Oncology (2020)

1547 Background: Due to persistent disparities in breast cancer mortality, there has been a renewed focus on investigating tumor biology. Deeper exploration has exposed distinctions in tumor biology based upon self-reported race and ancestry. The disparities associated with Triple Negative Breast Cancer (TNBC) across the modern African Diaspora suggests that there is a genetic ancestry connection between its aggressive tumor biology and clinical outcomes. Understanding this connection could hold the key to improving clinical outcomes in this group. Methods: We investigated 75 TNBC primary tumors using Self-Reported Race (SRR) groups: African American (AA, n = 42) and European American (EA, n = 33). Using best practices established by TCGA, we analyzed bulk RNA sequencing to measure changes in genome-wide expression levels. We next quantified global ancestry in a novel manner using RNAseq variants using 1000 Genomes as the reference data. We then identified African and European ancestry-associated genes using a logistic regression (adjusted FDR p &lt; 0.05) between quantified ancestry and gene expression levels. Results: We identified &gt; 150 genes associated with quantified African ancestry. We also found using quantified ancestry was a more robust method to screen for differentially expressed genes than SRR. Using an updated TNBC subtyping method, we noted higher incidences of Basal-like 2 tumors in AAs. Pathway analyses indicated several canonical cancer pathways; including, TP53, NFKB1 and AKT, have altered functionality in patients of African descent. For example, TP53-associated genes were activated in TNBC tumors of AA versus EA. This upregulation, rather than loss of function, is suggestive of polymorphic and/or ancestry-specific expression regulation, likely driven by population-private genetic variants. Lastly, we used TCGA data to validate a subset of African ancestry-specific genes that were upregulated in AA patients in our cohort. Specifically, PIM3, ZBTB22 and PPP2R4 each retained significant upregulation, in our cohort, but also TNBC tumors from TCGA (p = 0.0018, 0.023 and 0.022, respectively). Conclusions: Our study has uncovered ancestry-specific gene expression profiles in TNBC tumors. The distinct distribution of TNBC subtypes and altered functional oncologic pathways are evidence that biological underpinnings in TNBC can be driven by shared genetic ancestry. These findings emphasize the need to investigate patient populations of various ancestral origins in order to fully appreciate the molecular diversity in tumor biology for precision of disease management.