tbuckley/cabot-search huggingface dataset:
Real-world clinical outcomes in patients receiving cyclin-dependent kinase 4/6 inhibitors (iCDK 4/6) for hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer in Mexico.
Authors: Benigno Rodriguez, Lorena López Zepeda, Alejandro Noguez-Ramos, Daniela Vazquez Juarez, Christian Patricio Camacho Limas, Gabriela Olivia Regalado Porras, Ivonne Salcedo, Samuel Rivera, Alvaro Aguayo, Yazmin Carolina Blanco Vazquez, Angel Azael Lopez Galindo, Daniela Shveid Gerson, Fernando Perez-Zincer, Juan Alberto Serrano, José Fabián Martínez-Herrera, Guillermo Olivares, Alberto Villalobos, Cesar Gonzalez De Leon, Raquel Gerson
Journal: Journal of Clinical Oncology (2020)

e13053 Background: Breast cancer was the second most common malignant tumor diagnosed in 2018 worldwide, and the main cause of cancer death in women. In Mexico is the leading cause of cancer deaths, the most common molecular subtypes is HR+/HER2- (63%). The addition of iCDK 4/6 can enhance the benefit seen with endocrine therapy (ET) alone. In this work we will describe the experience in a “real world” model, of two tertiary-level hospitals in Mexico, with the use of iCDK 4/6 in a period of 3 years. Methods: Retrospective review of medical records of all consecutive pts with histological diagnosis of metastatic breast cancer HR+/HER2- and iCDK 4/6 treatment at our Institutions from July 2016 to January 2019. Clinical and pathological variables at diagnosis were recorded. Progression free survival was estimated using Kaplan-Meier method and survival distributions were compared using the Log-rank test. To assess association variables and progression we use Chi square. Results: 65 pts were treated, all with iCDK 4/6 in combination with ET, either aromatase inhibitor or irreversible estrogen receptor antagonist. 62 with palbociclib and 3 with ribociclib; Median age was 53 y/o (IQR 42-63), ECOG 0-1 (92.3%), 80% was metastatic recurrent disease, 92% of these patients received endocrine adjuvant treatment. Median estrogen receptor percentage was 90 (IQR 61-92), progesterone 50 (9-83), KI67 20 (10-30). The metastatic sites were bone (64.6%), liver (41.5%), nodal (33.8%), lung (21.5%), CNS (3.1%) and others (18.5%). 26 pts (40%) received iCDK 4/6 in the first line, 21 (32.3%) in the second line, and 27% in subsequent lines. Any grade of toxicity was presented in 44 pts (67.7%), Most common toxicities were neutropenia (63%), fatigue (16.9%), anemia (9.2%), grade 3-4 toxicities were presented in 21.5% and 17 pts (26.2%) required any dose adjustment. At the cut-off date, 28 pts (43.1%) had disease progression, median time to progression for the 65 pts was 10 months (1-84). OR for first line treatment vs subsequent lines was 0.14 (0.04-0.47, 95%, p = 0.001). OR for pulmonary metastases were 4.21 (1.15-15.31, 95%, p = 0.03), for other sites of metastasis were NS. Conclusions: Our outcomes suggest that the PFS is better when iCDK 4/6 are used as a first line treatment. Pulmonary metastases are may associated with poorly outcomes. In low- and middle-income countries, efforts should be focused on early therapy with iCDK 4/6.
Single-cell multiplexed proteomics to identify novel polyfunctional CD8+ T cell signatures induced by nivolumab in head and neck cancer patients after salvage surgery.
Authors: Shuchi Gulati, Sulsal Haque, Sarah Palackdharry, Aubrey Steele, Casey Allen, Vinita Takiar, Muhammad Kashif Riaz, Maria Lehn, Roman Jandarov, Chad Zender, Yash Patil, Alice L Tang, Brian Cervenka, Ammar Sukari, Misako Nagasaka, Trisha Michel Wise-Draper
Journal: Journal of Clinical Oncology (2020)

6576 Background: Immune checkpoint inhibitors (ICIs) are FDA approved for use in head and neck squamous cell cancer (HNSCC), however, only ~20% patients achieve a response. Identification of biomarkers of response or toxicity remains a challenge. Polyfunctional T-cells, or T-cells producing multiple cytokines, have been recognized as contributors to durable immunity against various cancers. However, their role has not been studied prospectively in HNSCC patients receiving ICIs. To look for an early predictor of response, we used single-cell functional proteomic profiling (IsoPlexis) on blood samples pre- and post- first dose of nivolumab (nivo) in patients on our phase-II study of locally recurrent HNSCC (NCT03355560). Methods: HNSCC patients who failed definitive radiation +/-chemotherapy and were subsequently treated with curative intent salvage resection were enrolled to receive 6 months of nivo beginning 4 to 11 weeks after surgery. Blood samples were collected before and after the first dose of nivo. Peripheral blood mononuclear cells were isolated, enriched for CD8+ T cells and using the 32-plex IsoCode technology, single-cell cytokine signals were captured and polyfunctional strength of CD8+ T cells was evaluated across four groups (effector, stimulatory, regulatory, inflammatory). A comparison analysis was performed between pre- and post- nivo treatment and between patients who relapsed (non-responders) vs those who did not (responders). Results: Thirty-three of 39 planned patients have been enrolled, of which 28 are evaluable and 5/28 (18%) developed recurrence. Median age is 68 years (range 51-85), 9/28 (32%) patients are female, 26/28 (93%) are white, disease sites include oropharyngeal 6/28 (21%), oral cavity 11/28 (39%) and larynx 11/28 (39%). Samples were evaluated at a median follow up of 5.9 months from enrollment. Single-cell analysis demonstrated a strong upregulation of polyfunctional human CD8+ T cell subsets in responders. Polyfunctional Strength Index (PSI) was enhanced in CD8+ T cells across the responders’ samples, composed largely of effector cytokines (granzyme-β, IFN-γ, MIP-1α, perforin, TNF-α). Conclusions: Single-cell functional proteomic analysis revealed significantly upregulated polyfunctional profiles and an increase in effector cytokines in patients who responded to nivo. This data provides important insights into PD-1 inhibitor triggered T-cell activity and may be used to predict response to ICIs in HNSCC patients using a blood test. Clinical trial information: NCT03355560 .
Three hundred patients with cerebrovascular disease within onset of 3 days were evaluated C-reaction protein level and cerebrovascular disease prognosis
Authors: Jun-qing Bai, Li-ming Yan, Guo-liang Yang, Li-na Wang, Hai-bin Yu, Xiao-li Ding, Qiu-hong Li
Journal: BMJ (2008)

Three hundred cerebrovascular disease (CVD) patients (disease onset <3 days) were evaluated for serum C-reactive protein (CRP) level at admission, and Scandinavian Stroke Scale (SSS) or Oxford Handicap Scale (OHS) at baseline and 3 months. Based on serum CRP levels, the participants were divided into group A [CRP(1.20 ±0.35)mg/L], group B[CRP(4.98 ± 1.08) mg/L] or group C[CRP (19.34±12.27)mg/L]. Our results showed that serum CRP level was positively correlated with SSS (r = 0.39 or0.43, both P<0.01) and OHS (r=0.40 or0.42, both P<0.01) at3 months. Thus, evaluating serum CRP level within 3 clays of disease onset might be helpful in predicting clinical outcomes of CVD patients.

Key words: 
C-reactive protein;  Cerebrovascular accident
The prevalence and associated factors of peritoneal dialysis-related staphylococcus peritonitis
Authors: Yuanfang Zou, Wanying Luo, Xiaodong Guan, Xingming Tang, Xiang Liang, Shaoqing Guo
Journal: BMJ (2014)

Objective To study the prevalence and associated factors of peritoneal dialysis-related staphylococcus peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients.Methods One hundred and ninty-two CAPD cases with peritoneal dialysis-related peritonitis in our peritoneal dialysis (PD) centers were retrospectively analyzed.The associated factors of peritoneal dialysis-related staphylococcus peritonitis were investigated through Logistic regression analysis.Results The prevalence of peritoneal dialysis-related staphylococcus peritonitis was 16(8.3％).The major strain was staphylococcus spidermidis (50.0％,8/16),and the cure rate was 75.0％ (12/16).One case died.Among those with peritoneal dialysis-related staphylococcus peritonitis,older age (OR =1.35,95％ CI 1.16-7.68,P =0.026),diabetes (OR =3.34,95％ CI 1.90-6.54,P ＜ 0.001),lower hemoglobin (OR =1.68,95％ CI 1.21-6.48,P =0.022) and lower albumin (OR =1.04,95％ CI 1.02-1.07,P =0.036) were independently associated with increased risk of peritoneal dialysis-related staphylococcus peritonitis.Conclusions Staphylococcus epidermidis peritonitis has higher incidence rate in CAPD patients.Older age,diabetes,lower hemoglobin and lower albumin are independently associated with increased risk of peritoneal dialysisrelated staphylococcus peritonitis.

Key words: 
Peritoneal dialysis, continuous ambulatory;  Peritonitis;  Staphylococcus;  Risk factors
Differentiation of liposomal irinotecan from dose-dense non-liposomal irinotecan in patient-derived pancreatic cancer xenograft tumor models.
Authors: Sandrine Barbier, Stephane Lezmi, Benjamin Beaufils, Adreanne Lortie, Marc Hillairet de Boisferon, Sophie Chaumeron, Anne Espirito, Stephan G Klinz, Arunthathi Thiagalingam, Florence Meyer-Losic
Journal: Journal of Clinical Oncology (2020)

e16724 Background: Liposomal irinotecan (ONIVYDE) is approved with 5-fluorouracil/leucovorin for metastatic pancreatic ductal adenocarcinoma (PDAC) post progression on gemcitabine-based therapy. The liposomal formulation prolongs payload residence time in the circulation and tumor lesions, where local conversion to the active metabolite SN-38 is thought to occur. The effect of the liposomal formulation on therapeutic index (TI) was assessed in patient-derived xenograft PDAC models (IM-PAN-001 [untreated tumor] and SA-PAN-077) in severe combined immunodeficiency mice. Methods: Liposomal (2.5, 10 or 50 mg/kg, intravenous [IV] 1 x weekly) and non-liposomal irinotecan (2, 5 or 10 mg/kg, IV 5 x weekly) were administered for 3 weeks (n = 8/group). Maximum tolerated dose (MTD) and clinically-relevant weekly doses (10 mg/kg, liposomal; 33 mg/kg, non-liposomal) of irinotecan were evaluated. TI was the ratio of MTD/lowest dose with anti-tumoral activity; time to reach tumor volume of 600 mm 3 (TTV600) was a proxy for overall survival. Tumor, plasma, gut and bone marrow were sampled for pharmacokinetics and safety assessment; DNA damage was evaluated via pH2AX and 53BP1 IHC. Results: The Table reports results of the more sensitive IM-PAN-001 model: TI of weekly liposomal irinotecan was 4-fold higher than for 5 x weekly non-liposomal irinotecan (TI was narrower for SA-PAN-077). For liposomal vs non-liposomal irinotecan in IM-PAN-001, TTV600 was longer at both MTD and clinically equivalent doses, and tumoral irinotecan levels were higher at MTD. High levels of DNA damage were present in most cancer cells in IM-PAN-001 compared to SA-PAN-077 one week after the last liposomal treatment cycle. Conclusions: In both PDAC models, TI was higher for weekly liposomal vs 5 x weekly non-liposomal irinotecan, suggesting potential benefits of the liposomal formulation in a clinical setting. [Table: see text]
Use of self-made drainage device in surgical procedure for prolapse and hemorrhoid operation
Authors: Hui Ye, Shu-juan Huang, Zhi-lin Gong, Qi-chang Zhou
Journal: BMJ (2013)

A total of 120 patients with Ⅲ/Ⅳ degree hemorrhoids were randomly divided into 3 groups. Self-made drainage(A group), traditional device(B group)and stuffing(C group) were used at the end of operation. The patient postoperative complications and satisfaction were observed and compared. The results showed that postoperative abdominal distension, pain, medical dressing dampness and satisfaction were better in A group than those in B and C groups(all P<0.01). Postoperative abdominal distention in B group was lighter than that in C group and medical dressing dampness less in C group than that in B group (all P<0.01). Thus the self-made drainage device may reduce the levels of postoperative abdominal distension, pain and medical dressing dampness and increase postoperative patient satisfaction.


Key words: 
Drainage, hemorrhoids; Procedure for prolapse and hemorrhoids
A Development Pathway Towards Precision Mental Health Care
Authors: Jaime Delgadillo, Wolfgang Lutz
Journal: JAMA Psychiatry (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Penehyclidime hydrochloride in treatment for patients with moderate and severe organophosphorus poisoning
Authors: Xu-fang Yu, Zhan-dong Huang, Jun Zhang
Journal: BMJ (2009)

One hundred and forty-nine patients with moderate and severe organophosphorus poisoning were treated in Fangshan District Hospital, Beijing during July 2005 to July 2007, 77 cases of them with intravenous atropine and intramuscular pyraloxime methylchloride and 72 with intramuscular penehyclidime hydrochloride plus pyraloxime methylchloride. Time of atrepinization, number of medication injection, time of symptom disappearance, recovery time of cholinesterase, length of hospital stay in those with penehyclidime hydrochloride plus pyraloxime methylchloride were all better than those with atropine and pyraloxime methylchloride (P<0.05). Percentage of atropine poisoning, atropine dependence, organophosphorus poisoning rebound and adverse reaction in those with penehyclidime hydrochloride plus pyraloxime methylchloride were lower than those in those with atropine and pyraloxime methylchloride (P< 0.05).

Key words: 
Cholinergic antagonists;  Poisoning
Two preventive interventions of postpartum hemorrhage
Authors: Xue-ye Gong, Wen-juan Zhang
Journal: BMJ (2013)

A total of 358 high-risk pregnant women were divided randomly into observation (A) and control (B) groups. Group A: 15ml 10% calcium gluconate was injected intravenously during the second stage of labor at full dilatation. And 10 U oxytocin was injected intramuscularly upon an immediate delivery of fetal anterior shoulder. Then 400 μg misoprostol was inserted into anus at 5 cm; Group B: 10 U oxytocin was injected intramuscularly upon an immediate delivery of fetal anterior shoulder. Then 400 μg misoprostol was inserted into anus at 5 cm. Statistically significant differences existed in the amount of bleeding loss after delivery for 2 h and 24 h (P 0.05). An intravenous infusion of calcium gluconate plus oxytocin and misoprostol after birth could reduce the rate of postpartum hemorrhage. Worthy of clinical application, this method has no effect upon Apgar score.


Key words: 
Postpartum hemorrhage; Calcium gluconate
Haploidentical hematopoietic stem cell transplantation with supplemental umbilical cord blood infusion in treatment of malignant hematological diseases
Authors: Zhenlan Du, Peng Chen, Rongmu Luo, Quanhua Liu, Xiaomei Zhang, Ya Wang
Journal: BMJ (2014)

Objective
To evaluate the efficacy of haploidentical hematopoietic stem cell transplantation (HSCT) with supplemental umbilical cord blood (UCB) infusion in treatment of malignant hematological diseases.


Method
Clinical data of 66 patients with hematological malignancies treated with HSCT in our hospital between January 2010 and May 2013, were retrospectively analyzed. Among them 25 cases received infusion of human UCB before HSCT (experimental group) and other 41 cases had no UCB injection before HSCT (control group).


Results
There were no differences in age, gender, donor type, disease categories, disease status before transplant between two groups (P>0.05). There was a significant difference in conditioning regimes between two groups (P<0.05), but no clinical implication. The infused mononuclear cell (MNC) count in experimental group was higher than that in control group (9.94±2.88×108/kg vs. 7.80±0.82×108/kg, P=0.00), while there were no difference in infused CD34+ cell count (5.46±3.54×106/kg vs. 3.54±1.60×106/kg, P=0.16). Neutrophil recovery time in experimental group was shorter than that in control group (13.7±2.9 d vs. 16.6±2.9 d, P=0.023). The incidences of grade Ⅲ-Ⅳ acute graft versus host disease (aGVHD, P=0.036), bacterial infection(P=0.001)and fungal infection(P=0.001)and hemorrhagic cystitis (P=0.00)in experimental group were lower than those in control group. There were no significant differences in platelet recovery time(P=0.43), the incidence of grade Ⅰ-Ⅱ aGVHD(P=0.27), implanted syndrome(P=0.24), sinusoidal obstruction syndrome(P=0.57)and viraemia(P=0.31)between two groups.


Conclusion
HSCT with supplemental infusion of human UCB may alleviate the degree of aGVHD, but the long-term outcome remains to be studied.


Key words: 
Hematopoietic stem cell transplantation; Fetal blood; Hematologic neoplasms
Design and rationale of MASTERKEY-115 phase II trial of talimogene laherparepvec (T-VEC) with pembrolizumab (pembro) in patients with advanced melanoma who progressed on prior anti-programmed cell death-1 (anti-PD-1) therapy.
Authors: Jason Alan Chesney, Mohammed M. Milhem, Marya F. Chaney, Priya Gokani, Wendy Snyder, Caroline Robert
Journal: Journal of Clinical Oncology (2020)

TPS10079 Background: Treatment options are limited for patients with advanced metastatic or unresectable melanoma, especially after anti-PD-1 failure. T-VEC is an intralesional oncolytic viral immunotherapy designed to selectively replicate in tumor cells and induce local and systemic antitumor response. Pembro promotes T cell activity by blocking PD-1 receptors. Combining T-VEC and pembro may produce robust antitumor activity by increasing T cell activation and blocking T cell inhibition, with a tolerable safety profile. The MASTERKEY-115 trial will evaluate safety and efficacy of T-VEC combined with pembro in patients with advanced melanoma who experienced progressive disease (PD) on prior anti-PD-1 therapy. Methods: NCT04068181 is a phase 2, open-label, single-arm, multicenter trial of T-VEC with pembro in patients with advanced melanoma and PD on prior anti-PD-1. The study is expected to enroll approximately 100 patients and comprises 4 cohorts. Cohorts 1 and 2 will receive anti-PD-1 in a locally recurrent or metastatic setting and experienced PD within 12 weeks of the last anti-PD-1 dose (Cohort 1: PD or stable disease prior to confirmed PD; Cohort 2: complete or partial response prior to confirmed PD). Cohorts 3 and 4 will receive adjuvant anti-PD-1 and were disease-free for &lt; 6 months (Cohort 3) or ≥ 6 months (Cohort 4) prior to confirmed PD. Enrollment criteria include adults with histologically confirmed unresectable or metastatic stage IIIB–IVM1d melanoma, measurable and injectable disease, ECOG PS 0-1, and prior anti-PD-1 (≥ 2-3 consecutive cycles within 8 weeks, immediate prior treatment before enrollment). The primary endpoint is objective response rate per modified RECIST. Key secondary endpoints assess efficacy (objective response rate, best overall response, complete response rate, response duration, durable response rate, disease control rate, progression-free survival, overall survival), safety (incidence of treatment-emergent and treatment-related adverse events, abnormal laboratory tests), and time to subsequent anticancer therapy. The study began enrolling patients in January 2020 and enrollment is ongoing. Clinical trial information: NCT04068181.
Effect of low dose heparin on coagulation index and therapeutic outcomes in premature infants with sepsis
Authors: Weiwei Liu, Ying Jiao, Liying Zou, Dongren Han
Journal: BMJ (2019)

Objective
To investigate the effect of low dose heparin on blood coagulation and therapeutic outcomes in premature infants with sepsis.


Methods
Clinical data of 69 septic preterm newborns weighting less than 1 500 g treated in Beijing Obstetrics and Gynecology Hospital were retrospectively analyzed. Among them, 29 infants received heparin therapy (6 U/kg, q 8 h, for 3 d,then q12 h, heparin group) and 40 infants did not receive heparin therapy (control group), the coagulation index and therapeutic outcomes were compared between two groups.


Results
The coagulation indexes PT, TT, APTT and D dimer in heparin group were all significantly lower than those in control group [(15.5±3.5) s vs. (19.0±3.9) s, (15.4±3.5) s vs. (18.8±3.5) s, (47.5±8.6) s vs. (58.4±18.1) s, (1.7±0.8) mg/L vs. (2.6±1.9) mg/L; t=-3.815,4.275,-3.004,-2.459, P<0.05]. The overall clinical effective rate in heparin group was significantly higher than that in control group (86.2% vs. 60.0%, χ2=4.408, P<0.05).


Conclusion
Low dose heparin can significantly improve the blood coagulation function and improve the therapeutic effect of premature infants with sepsis.


Key words: 
Heparin; Sepsis; Premature infant; Extremely low birth weight infant