tbuckley/cabot-search huggingface dataset:
Impact of COVID-19 on cancer caregivers: Results from the Global Carer Well-being Index.
Authors: Karen V.L. Turpin, Elizabeth Foland, Taylor Patton, Jeremy Guterl, Marni Zapakin, Jasmine Greenamyer
Journal: Journal of Clinical Oncology (2022)

460 Background: Caregiver burden has been intensified by the COVID-19 pandemic. The Carer Well-being Index is a global research study commissioned by Embracing Carers, a partnered initiative with nine global caregiving organizations. The study sought to explore and delineate the impact of the pandemic on the health and well-being of caregivers across the globe, including those caring for persons with cancer. Methods: The survey was conducted via online and phone methodologies in September and October 2020, with over 9,000 unpaid carers across 12 countries, including the United States and Canada. Unpaid carers were defined as those who care for someone with a long-term illness (e.g., cancer), physical disability (e.g., spinal cord injury), or cognitive/mental condition (e.g., Alzheimer’s). The base sample size for cancer caregivers from the global surveyed population was n=1035. Statistically significant differences between cancer carers and non-cancer carers were evaluated using the Chi-square test with p ≤ 0.05. Results: 63% of all caregivers were women, with a 60/40 female to male split in the cancer carer group. While the average age of started caregiving was 37.2 years, and 39.0 in cancer carers, caregivers caring for someone with cancer were more likely than the average caregiver to be in the 60+ age group. Compared to non-cancer caregivers surveyed, a higher percentage of cancer caregivers became carers in the last year (26 vs 13% of non-cancer caregivers). Providing emotional support, managing doctor appointments, preparing meals, home maintenance and housekeeping, transportation, and giving/managing medications were more likely to be among cancer caregivers' primary responsibilities, compared to non-cancer caregivers. Cancer carers were significantly more likely than non-cancer carers to have reported negative impacts because of COVID on their emotional/mental, physical, and financial health, and paid work responsibilities. Overall, cancer caregivers were significantly more likely to report that COVID has made caregiving harder than non-cancer caregivers (71 vs 63%), and were more likely to report never receiving support from a variety of organizations, such as insurance organizations (71 vs. 66% non-cancer caregivers) and local/state government (73 vs. 66%). Of note, cancer carers were more likely to report a positive impact on the relationship with the person being cared for (61 vs. 56%). Conclusions: These results highlight the burdens that have been intensified for cancer carers. Actions are needed to help with health and well-being such as offering and promoting mental health services, respite care; providing financial support to take leaves from paid work, access to equipment and services such as housecleaning. By working together with health care providers, organizations, and government on these types of initiatives, the burden upon cancer caregivers can be lessened.
Changes in body composition during neoadjuvant platinum-based chemotherapy associations prior to radical cystectomy: Implications for chemotherapy-associated adverse events and oncologic outcomes.
Authors: Reno Maldonado, Florian J. Fintelmann, Jan Peter Marquardt, Ryan Blair O'Malley, Sarah K. Holt, Steven Ngo, Leonidas Nikolaos Diamantopoulos, Grace Laidlaw, George R. Schade, Daniel W. Lin, Jonathan L. Wright, John L. Gore, Yaw A. Nyame, Petros Grivas, Evan Y. Yu, Robert B. Montgomery, Andrew Caleb Hsieh, Todd Yezefski, Michael Thomas Schweizer, Sarah P. Psutka
Journal: Journal of Clinical Oncology (2022)

476 Background: Low skeletal muscle index (SMI) is associated with an increased risk of mortality in muscle-invasive bladder cancer (MIBC) and chemotherapy-related adverse events (AE) across numerous other malignancies. Small case series suggest neoadjuvant chemotherapy (NAC) is associated with a significant decline in SMI in patients with MIBC. However, limited data exists regarding changes in fat mass during NAC. Herein, we examine changes in SMI, visceral fat index (VFI), and subcutaneous fat index (SFI) in patients receiving NAC for MIBC before radical cystectomy (RC). We describe associations between body composition changes and NAC-associated AE and all-cause mortality (ACM) in patients with MIBC. Methods: Retrospective review of patients with MIBC (≥pT2 N0/x/1 M0) who received NAC (2006-2019). Patients with digitized abdominal computed tomography scans (CT) within 75 days prior (T1) and 75 days following completion (T2) of NAC were included. We segmented and calculated the indices (cm 2 /m 2 ) for SMI, VFI, and SFI at the third lumbar vertebra level at T1 and T2 using validated methodology. Associations with AE during NAC and ACM were evaluated with multivariate logistic regression and Cox proportional hazards models. Results: Included 170 patients, median age 63 years receiving a median of 4 (IQR 3-5) cycles of Gemcitabine/Cisplatin (52%), MVAC (28%), or other NAC (20%). Absolute and relative changes in SMI, VFI, and SFI over a median of 112 days (IQR 94-146) between measurements are presented in the Table. 117 (69%) patients experienced grade ≥3 chemotherapy-related AE. No associations between baseline body composition or change in body composition during NAC with chemotherapy-related AE. T1 SMI (HR: 0.98; 0.97-0.99, p = 0.008), as well as T2 SMI (HR: 0.98; 0.96-0.99, p = 0.003), T2 VFI (HR: 0.99; 0.99-1.0, p = 0.05) and T2 SFI (HR: 0.99; 0.98-1.0, P = 0.03) were associated with ACM after adjusting for age, clinical T and N stage, and performance status. Conclusions: Patients undergoing NAC prior to RC experienced a 6.4% decrease in SMI and a 5.2% decrease in VFI during an average of 112 days. Chemotherapy-related AE were not associated with a change in body composition. Baseline SMI and T2 SMI, SFI, and VFI were associated with ACM on multivariable analysis. Future work is needed to understand the mechanisms underpinning such changes and the extent to which potentially detrimental changes in body composition may be mitigated before surgery.[Table: see text]
Intrinsic hazard of breech presentation.
Journal: BMJ (1981)

range improved from 23% in 1976 to 68% in 1979.It seems likely.that more caesarean sections were performed, especially in this extremely low birthweight group, during the latter years of the study.The fact that both vertex and breech delivery in the 750-1000 g group carry an equally high mortality rate when compared with caesarean section lends further support to the suspicion that many factors other than breech presentation are responsible for the differences in survival rate.This paper does not strengthen the case for a policy of caesarean section for all cases of breech presentation from 26 to 34 weeks.It does, however, lend further support to the case for a randomised controlled trial of caesarean section for preterm breech presenta- tion, which was called for in this journal in 1979.
Semen analysis
Authors: Rune Eliasson
Journal: Environmental Health Perspectives (1978)

In view of the well known sensitivity of the seminiferous epithelium to various stress factors and to chemicals one would expect that semen analyses would be part of many screening programs to detect dangerous chemicals and environmental hazards. This is not the case, and our knowledge about the production and functional properties of human spermatozoa is mainly based on analyses of specimens from men with barren marriages. A more common use of semen analyses should enable us to better define the normal limits for many of the potentially relevant variables. Due consideration must, however, also be given the time for spermatogenesis and for transit through the epididymis as well as the influence of seminal plasma factors on many functional properties of the spermatozoa. From the scanty information available one can already now presume that careful analyses of motility and morphology of the spermatozoa under standardized conditions will be of help in the early detection of environmental hazards. A more common use of methods for the assessment of such functional properties of the spermatozoa as structural stability, membrane permeability, metabolism, and resistance to physical stress will give additional information about the effects of chemicals and other factors. To exploit these potential methods for the early detection of environmental hazards there is, however, also a need of a changed attitude towards semen analysis from the medical profession as well as from the public.
From the NCHTC: Evaluation of therapeutic apheresis for rheumatoid arthritis
Journal: JAMA (1981)

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Comparison of two doses of cimetidine and placebo in the treatment of duodenal ulcer: a multicentre trial.
Authors: K Bardhan, D Saul, Rotherham Hospital, J Edwards, P Smith, Llandough Hospital, M Fettes, J Forrest, R Heading, R Logan, M Dronfield, M Langman, W Larkworthy, Nocton Hall, S Haggie, J Wyllie2, C Corbett, H Duthie, I Fussey, C Holdsworth, G Balmforth, T Maruyama
Journal: Gut (1979)

Abstract Endoscopy, clinical assessment, and laboratory studies were used to compare, in a double-blind multicentre trial, the effects on patients with duodenal ulceration of treatment for four weeks by either placebo or 1 g/day cimetidine, or 2 g/day cimetidine. Ulcer healing occurred in 28% of patients on placebo, 61% of patients on 1 g cimetidine daily, and 70% of patients on 2 g cimetidine daily. Thus cimetidine conferred an advantage over placebo, but the effects of the two doses of cimetidine were not shown to be different. Symptomatic improvement in patients given cimetidine was usually marked and occurred early. Patients were required to report all symptoms, but the only symptom which might have been caused by cimetidine was headache in 5% of patients. Biochemical studies showed significant (though slight) rises in serum uric acid, and serum creatinine but no significant changes occurred in the serum levels of liver enzymes. This study confirms that 1 g is a suitable daily dose of cimetidine for the treatment of duodenal ulceration.
Abstract 193: Intraosseous Transfusion With Liposome-Encapsulated Hemoglobin (HbV) Comparably Improves Rat Survival and its Arrythmogenesis Undergoing Progressive Lethal 85% Hemorrhage With Central Venous Infusion: Possible Implication for Pre-Hospital Settings
Authors: Bonpei Takase, Yuko Higashimura
Journal: Circulation (2018)

Liposome-encapsulated hemoglobin (HbV) can serve as blood substitute in hemorrhagic shock (HS). To investigate the resuscitation effect of HbV through intraosseous transfusion (IO) on lethal hemorrhage and its efficacy on myocardial arrhythmogenesis, optical mapping analysis (OMP) and electrophysiological study (EPS) were performed in graded blood exchange up to 85% blood loss in rats. And it was compared with central venous infusion (CVI). Total 90 rats were randomly allocated into 6 subgroups as followings; through IO or CVI, gradually exchanged blood with 5% albumin (Alb-IO/CVI-groups), exchanged with washed rat erythrocyte (wRBC-IO/CVI-groups) and with HbV (HbV-IO/CVI-groups). Survival effects were examined in each six rat groups. After excising the heart, OMP and EPS were performed. All rats died in Alb-IO/CVI-groups whereas excellent and comparably survived for following &gt;48-hours in wRBC-IO/CVI-groups and HbV-IO/CVI-groups (Figure 1). OMP revealed impaired (prolonged) action potential duration (APD) dispersion in LV in Alb-IO/CVI-groups. In contrast, myocardial APD dispersions in LV were substantially attenuated in HbV-IO/CVI-groups and wRBC-IO/CVI-groups (Figure 2). Lethal arrhythmias (VT/VF) were provoked by EPS in Alb-IO/CVI-groups. No VT/VF was induced in both HbV-IO/CVI-groups and wRBC-IO/CVI-groups. Conclusions: IO vascular access could a reliable bridging method to resuscitate lethal HS by HbV. This suggests that IO with HbV resuscitation might be useful in pre-hospital settings in HS through preventing lethal arrhythmias.
Assessing physician prescribing behaviors in first-line (1L) advanced renal cell carcinoma (aRCC): A case-based study.
Authors: Ajeet Gajra, Yolaine Jeune-Smith, Ulka N. Vaishampayan, Skyler Rupard
Journal: Journal of Clinical Oncology (2022)

355 Background: Over the past decade, immune checkpoint inhibitors (ICIs) have become foundational to aRCC management. Tyrosine kinase inhibitors (TKIs) remain a mainstay, resulting in the potential for ICI/TKI combination regimens. Four ICI/TKI combinations (pembrolizumab/axitinib [PA], nivolumab/cabozantinib [NC], pembrolizumab/lenvatinib [PL], and avelumab/axitinib [AA]) have shown promising results compared to single-agent sunitinib in randomized clinical trials (KEYNOTE-426 [KN426], CheckMate 9ER [CM9ER], CLEAR, and JAVELIN RENAL 101 [JR101], respectively); national guidelines recommend them as 1L options. Further, an ICI-based regimen of nivolumab/ipilumumab (NI) is a treatment option for poor-risk RCC based on CheckMate 214 (CM214) results. We sought to understand how community oncologists perceive data from these trials and what aspects influence their clinical decisions. Methods: In May 2021, medical oncologists experienced in treating aRCC were presented with key results from these trials and 2 clinical vignettes. Treatment preferences and reasons for decisions were captured via an audience response system. Responses were aggregated and analyzed using descriptive statistics. Results: A total of 103 U.S. medical oncologists participated; most risk-stratify their patients with either IMDC (44%), MSKCC (34%), or both (14%). When presented with simulated case studies, most (76%) indicated they are not likely to order PD-L1 testing, yet 81% will treat with an ICI-based regimen. Participants are more likely to prescribe ICI/TKI over ICI/ICI (65% vs 47%) in favorable-risk aRCC. Yet in poor-risk RCC, they are more likely to prescribe ICI/ICI over ICI/TKI (52% vs 15%). Among ICI/TKI regimen, participants showed a small preference toward PA over NC for both the poor-risk (21% vs 20%) and intermediate-risk (30% vs 23%) patient case. In the favorable-risk case, PA was significantly preferred over NC, 46% vs 19%. Most participants were aware of the trial data (91% KN426, 82% CM9ER, 57% CLEAR, 96% CM214); and more found the data from CM9ER most compelling compared to KN426 and CM214 (32%, 29%, and 23%, respectively). The participants viewed trials that met primary or survival endpoints as strong. Major limitations in each trial commonly identified were trial design (KN426, 27%); short follow-up (CM9ER, 48%); short follow-up and no OS data (CLEAR, 39% and 38%, respectively), and high discontinuation rate (CM214, 42%). Conclusions: Providers typically will treat aRCC patients with ICI-based regimens regardless of PD-L1 status and are more likely to prescribe an ICI/TKI regimen for favorable-risk and an ICI/ICI regimen for poor-risk aRCC. Meeting primary endpoints is a strong influencer in providers’ decision-making. Given the nonsignificant difference in preference for PA over NC, further research is needed to assess factors influencing providers’ decisions.
Immuno-oncology (IO) combinations +/- VEGF targeted therapy (VEGF TT) in patients (pts) with advanced mit family translocation renal cell carcinomas (tRCC): Results from an international multicenter study.
Authors: Omar Alhalabi, Jonathan Thouvenin, Sylvie Negrier, Yann-Alexandre Vano, Luca Campedel, Elshad Hasanov, Ziad Bakouny, Andrew Warren Hahn, Mehmet Asim Bilen, Toni K. Choueiri, Srinivas Raghavan Viswanathan, Kanishka Sircar, Laurence Albiges, Gabriel Malouf, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2022)

343 Background: IO combinations are standard of care for first-line therapy of clear-cell RCC; however, non-clear cell histologies including tRCC were not included in the registrational trials. We previously reported a modest efficacy (objective response rate [ORR] &lt;20%) with IO monotherapy (PD-1 blockade) in tRCC (Boilève et al, JITC. 2018). The efficacy of IO combinations +/- VEGF TT has not been reported. Methods: This is a retrospective, international, multicenter study of pts with tRCC treated with IO-IO or IO+VEGF TT at 11 centers in the US, France, and Belgium. Only pts with confirmed TFE3 or TFEB translocation by fluorescent-in-situ hybridization (FISH) were included. ORR and progression-free survival (PFS) were assessed by RECIST. Overall survival (OS) was assessed by Kaplan-Meier methods. OS was measured from initiation of therapy till death or last follow up. We also assessed the association between OS and baseline prognostic variables. Results: 29 patients with metastatic tRCC were included in this analysis. Median age at starting therapy was 38 (IQR 27, 53) years. Female:Male ratio was 0.9:1. FISH revealed a translocation involving TFE3 and TFEB in 22 and 7 patients, respectively. Most frequent metastatic sites at diagnosis were lungs (76%), liver (52%), retroperitoneal adenopathy (48%), and bone (38%). IMDC risk at diagnosis was favorable (31%), intermediate (45%) and poor (24%). Combinations of IO+VEGF TT and anti-PD1 (L1) + anti-CTLA-4 (IO+IO) were used in 11 and 18 pts, respectively. 17 (59%) pts received IO combinations as 1L, 7 (24%) pts as 2L and 5 (17%) pts as ≥3L. ORR in the IO+IO group was 1/18 (5.5%), while in IO+VEGF TT group was 4/11 (36%). For 20 (69%) pts, progressive disease was the best overall response. At a median follow-up of 12.9 months (mo), median PFS was 3.2 mo and median OS was 13.5 mo for all 29 pts (Table). Median PFS in the IO+IO group was 2.8 mo, and 5.4 mo in IO+VEGF TT group (HR=0.81, 95% CI: 0.35-1.84). Conclusions: In this small retrospective study of tRCC, IO+IO therapy produced modest activity based on low ORR and short PFS while IO+VEGF TT produced numerically higher ORR and longer PFS. Insights into the biological basis of tRCC are necessary to develop more effective therapies for this rare and aggressive RCC variant.[Table: see text]
Incomplete Conflict of Interest Disclosures
Authors: Charles Fuchs, Eli Lilly
Journal: JAMA Oncology (2019)

Yin Cao, MPH, ScD; Reiko Nishihara, PhD; Kana Wu, MD, PhD; Molin Wang, PhD; Shuji Ogino, MD, PhD; Walter C. Willett, MD, DrPH; Donna Spiegelman, ScD; Charles S. Fuchs, MD, MPH; Edward L. Giovannucci, MD, MPH, ScD; Andrew T. Chan, MD, MPH
Addendum
Journal: American Journal of Hematology (1991)

Since this paper was written, a report has described an Italian family in which the father is a silent carrier of P-thalassemia with the +ATA/-T mutation described here (Mum et al., 1990.Blood 76:2164-2165).The mother is also a carrier, and three children exhibit thalassemia intermedia.Thus this new case, in addition to the Albanian silent carrier and the Indian haplotype, is another example of the +ATA/-T mutation associated with reduced P-globin synthesis.
Real-world treatment patterns among patients with metastatic castration-resistant prostate cancer (mCRPC) in the US.
Authors: Elisabetta Malangone-Monaco, Weiyan Li, Virginia Noxon, Shan Jiang, Suvina Amin, Sameer Ghate, Umang Swami, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2022)

49 Background: mCRPC is an incurable disease with poor prognosis. Though multiple treatments such as novel hormonal therapies (NHT: abiraterone [abi], enzalutamide [enza], docetaxel [doce], cabazitaxel [caba], sipuleucel-T [Sip-T] etc.) are approved, real-world data regarding treatment sequencing are lacking. This study assesses the real-world treatment patterns within the context of FDA-approved life-prolonging treatments for mCRPC. Methods: The IBM MarketScan database was used to identify newly diagnosed (incident) mCRPC patients from 1/1/2014-5/31/2020. Adult males were required to have a diagnosis of PC, and subsequently evidence of metastasis and castration (medical or surgical). Incident mCRPC status (index) was determined 3 ways: 1) treatment with an NHT within 3 months after castration and an FDA-approved mCRPC treatment ≥3 months after NHT; 2) first FDA-approved treatment ≥6 months after castration; 3) first FDA-approved treatment 3-6 months after castration and a second FDA-approved treatment ≥3 months after treatment. Lines of therapy (LOT) were measured in the variable-length follow-up of ≥1 month and consisted of all drugs observed within 28 days of first observed treatment. Duration of therapy was measured as start of line to start of next line or end of enrollment. Results: A total of 2,912 mCRPC patients met all study criteria and received ≥1 LOT. Among those, 48.7% had ≥2 LOT, and 21.8% had ≥3 LOT. Patients were an average age of 71 years at index and used leuprolide (87%), abi (10%), doce (9%) and enza (8%) prior to index. In mCRPC the most common observed first line (1L) monotherapy regimens were abi (35%), enza (34%), and doce (14%). The most common observed second-line (2L) treatments were enza (36%), abi (27%), and doce (14%). Mean duration of 1L was 292 days compared to 245 days in 2L. The most frequently observed treatment sequences (1L to 2L) are reported in the table. Opioids (62%) and denosumab (47%) use was common in mCRPC patients. Conclusions: Among mCRPC patients, NHTs were the most common 1st and 2nd LOTs and alternate NHT after a first NHT was the most common sequence. With rapidly evolving treatment options in metastatic prostate cancer, these data can help guide estimation of eligible patients for different clinical trials. Further studies are needed to understand the high attrition from 1L to subsequent lines of therapy, the reasons for treatment preference and impact on clinical outcomes with different treatment sequencings.[Table: see text]
Impact of quorum sensing signaling molecules in gram-negative bacteria on host cells: current understanding and future perspectives
Authors: Yingping Xiao, Huicong Zou, Jingjing Li, Tongxing Song, Wentao Lv, Wen Wang, Zhenyu Wang, Shiyu Tao
Journal: Gut Microbes (2022)

Quorum sensing is a molecular signaling-based communication mechanism in prokaryotes. In the basic mode, signaling molecules released by certain bacteria are sensed by intracellular receptors or membrane-bound receptors of other members in the community, leading to the collective isogenic signaling molecule synthesis and synchronized activities. This regulation is important for the symbiosis of the bacterium with the host, as well as virulence and biofilm formation. Notably, quorum sensing signaling molecules are not only able to control microbial community behavior but can likewise regulate the physiological status of host cells. Here, we provide a comprehensive review of the importance of quorum sensing signaling molecules in gram-negative bacteria in regulating host cell function and gut health, and suggest possible opportunities for application in combating human and animal diseases by blocking the pathways through which quorum sensing signaling molecules exert their functions.