tbuckley/cabot-search huggingface dataset:
Disseminated Sclerosis
Authors: M. Kremer
Journal: BMJ (1958)

It is still unfortunately true that there is no specific remedy in disseminated sclerosis, but it would be very wrong indeed for this reason to abandon these patients without treatment of any kind, for much can be done to give symptomatic relief.As important as anything else in the treatment of this condition is the attitude of the doctor.There is still some ignorance in the profession of the natural history of the disorder, and once the diag- nosis is made a feeling of pessimism may overwhelm the practitioner, who feels he is faced with a hopeless patient soon to be reduced to a life of chronic incap- acity and needing almost full-time care.That this is not the case is by no means sufficiently widely known.The frequency of the disease in Great Britain is about one in 2,000 of the population; it varies in different counties.There are therefore a large number of sufferers, and it is clear at once that there are not that number of severely incapacitated patients in this country suffering from disseminated sclerosis.Many of these patients have long periods of remission often lasting many years.There are others whose disorder is mild, and, while they may have many abnormal signs in the nervous system, yet disorder of function and impairment of useful life are slight.An explanation to the intelligent patient along these lines may be very helpful; it may prevent him from feeling that the doctors are abandoning him and stop him and his relations from wandering round seeking help which is not available. Lines of AftackMany treatments of the disease have been tried, but assessment of results is impossible except on a very long- term basis, as any therapy may coincide with a natural remission.The major lines of attack are as follows.Vaccines.-Thelatest of these is the Shubladze-Margulis vaccine from the U.S.S.R.There is no evidence yet avail- able that this has any effect on the disease and it is
Abstract 330: LDK378 Attenuates Macro and Microcirculation in a Sepsis Rat Model Induced by Cecal Ligation and Puncture
Authors: Weiwei Ge, Zhengfei Yang, Qiaohua Hu, Xuefen Liu, Qin Ling, Jennifer Bradley, Mary Ann Peberdy, Joseph Ornato, Wanchun Tang
Journal: Circulation (2018)

Background: Sepsis is a systemic inflammatory response syndrome caused by severe infections. Myocardial dysfunction has been associated with increased mortality in septic patients. Previous studies have demonstrated that LDK378, a second-generation ALK inhibitor, is a potential anti-inflammatory mediator. We investigated the effects of LDK378 on macro and microcirculation in a rat model of cecal ligation and puncture (CLP) induced sepsis. Hypothesis: LDK378 attenuates the deleterious effects of sepsis on macro- and micro- circulation in CLP induced septic rats. Method: Fifteen male rats weighing between 450-550g were randomized into three groups: Sham, CLP, and CLP+LDK378. Our rat sepsis model was induced by 50% cecum ligation and two punctures with a 20-gauge needle. LDK378 (20mg/kg) was administered intraperitoneal (IP) to animals at 0h, 24h and 48 hours after CLP operation in the CLP+LDK378 group. Cardiac output (CO), mean arterial pressure (MAP); sublingual microcirculation including perfused small vessel density (PVD) and microcirculatory flow index (MFI) were measured at 6h, 30h and 54h after CLP. Results: Significant reduction in CO, MAP, MFI and PVD were observed in both CLP and CLP+LDK378 groups at 6h, 30h and 54h. However, the levels of CO, MAP, MFI and PVD reduction were significantly better in the CLP+LDK378 group when compared with the CLP group at 30h and 54h after CLP. Conclusion: LDK378 attenuates macro and microcirculation parameters in our rat model of sepsis.
Nephrotic syndrome.
Authors: J. S. Cameron
Journal: BMJ (1970)

If glomerular damage leads to persistent, heavy proteinuria then a nephrotic syndrome will appear-that is, heavy pro- teinuria, a low serum albumin, and oedema.Thus the group of patients with the nephrotic syndrome will merge with those showing heavy proteinuria but no oedema.Moreover, the syndrome may have many underlying disease processes, since many conditions can precipitate heavy proteinuria.A simple classification of these glomerular appearances was given in last week's article, while the principal causes of the nephrotic syndrome are listed in Table I.TABLE I.-Principal Causes of
<i>Fusobacterium</i> Travels with Colorectal Cancer Cells
Journal: Cancer Discovery (2017)

Fusobacterium is enriched in colorectal cancer, but until now it has been unclear whether these bacteria drive tumorigenesis. A recent study shows that colorectal cancer cells take their microbiomes with them as they metastasize-and that targeting Fusobacterium with antibiotics reduces tumor growth in mice xenografts.
Dacomitinib Beats Gefitinib for EGFR+ NSCLC
Journal: Cancer Discovery (2017)

The irreversible EGFR inhibitor dacomitinib reduced the chance of lung cancer progression compared with an older, first-generation EGFR inhibitor, gefitinib, in a phase III trial. As reported at the 2017 American Society of Clinical Oncology Annual Meeting, the experimental drug also increased toxicity, which could limit its use, especially with a safer, more effective third-generation EGFR inhibitor not far behind in the development pipeline.
Factors Affecting Yield of Genetic Testing of Sudden Deaths in Young Individuals—Reply
Authors: Gregory Webster, Alfred L. George, Elizabeth M. McNally
Journal: JAMA Cardiology (2022)

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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 Cardiology journal
Comments on the CAIRO4 Trial Secondary Outcomes Report
Authors: Felix Hammett, Giordano Perin, Saba Balasubramanian
Journal: JAMA Surgery (2022)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 Surgery journal
Bureau of Investigation
Journal: JAMA (1942)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Association of renal cell carcinoma (RCC) metastatic to pancreas with a distinct molecular profile and immune cell population.
Authors: Ryan S. Chiang, Arya Ashok, Elizabeth Mauer, Alex Barrett, Christian R Hoerner, Osama A Khan, Chia-Sui Kao, Sumit Shah, Sandy Srinivas, Alice C. Fan, Ali Raza Khaki
Journal: Journal of Clinical Oncology (2022)

366 Background: RCC may metastasize to diverse sites, which confers variable prognosis and treatment response. Pancreatic metastases in RCC have been associated with indolent biology, low genomic instability and decreased inflammation, which may lead to worse responses to immunotherapy. To further investigate this phenomenon, we compared the genomic landscape and immunotherapy biomarkers of metastatic RCC patients with and without pancreatic metastases. Methods: We identified a cohort from the de-identified Tempus database, consisting of patients with metastatic RCC who received next generation sequencing via the Tempus|xT assay (DNA-seq of 648 genes at 500x coverage; whole-exome capture RNA-seq). Records were included if patients had RCC diagnosis and metastases to at least one of: pancreas, liver, brain, or lung (regardless of the presence of other metastases). RCC diagnosis and metastatic sites were determined from abstracted clinical notes received at the time of sequencing. If individuals had multiple xT results, the results from the most recent sample were included (irrespective of tissue site). We compared the prevalence of somatic gene alterations (using false discovery rate corrected q-values) and immunotherapy markers among records with vs without pancreatic metastases. Statistical significance was determined via Wilcoxon rank-sum tests or Chi-squared/Fisher’s exact tests. Results: 654 patients (median age 61, 30% female, 62% clear cell) with metastatic RCC were included. 58 harbored pancreatic metastases and 596 had metastases to sites other than pancreas (36 brain, 88 liver, 358 lung, 114 brain/liver/lung combinations). Females had a significantly higher representation in the group with pancreatic metastases (43% vs 29%, p = 0.02). The group with pancreatic metastases had significantly more PBRM1 alterations (52% vs 25%, q &lt; 0.001), and trended towards more prevalent copy number loss of ALK (22% vs 10%, q = 0.06) and NTRK3 (16% vs 6%, q = 0.08) and less prevalent alterations in CDKN2A (3% vs 13%, q = 0.08), BAP1 (2% vs 13%, q = 0.06) and MTAP (0% vs 9%, q = 0.06). Individuals harboring pancreatic metastases had similar MSI status and TMB, but had lower rates of PD-L1 positivity, lower proportions of B-cells and higher proportion of NK cells in immune cell composition (Table). Conclusions: RCC patients with pancreatic metastases have a distinct molecular profile and lower rates of PD-L1 positivity, which suggests a unique disease biology and potential non-immunogenic phenotype. Further investigation and prospective validation is needed to determine immunotherapy outcomes in this population.[Table: see text]
Abstract 121: The Influence of Age, Race, and Ethnicity on Public Automated External Defibrillator Use and Outcomes of Pediatric Out-of-Hospital Cardiac Arrest in the United States: An Analysis of the Cardiac Arrest Registry to Enhance Survival (CARES)
Authors: Heather Griffis, Lucy Wu, Maryam Naim, Joshua Tobin, Bryan McNally, Kimberly Vellano, Linda Quan, David Markenson, Richard Bradley, Joseph Rossano
Journal: Circulation (2018)

Introduction: Automated external defibrillators (AEDs) are an important link in the chain of survival following out-of-hospital cardiac arrest (OHCA). While the use of AEDs are clearly beneficial for OHCA in adults, there are few data on the overall use and outcomes of public AED use in children. Hypothesis: AED use is uncommon in children and associated with neurologically favorable survival. Methods: We conducted an analysis of the Cardiac Arrest Registry to Enhance Survival database. Inclusion criteria were age ≤ 18 years of age, public arrests, and non-traumatic OHCA from January 1, 2013 through December 31, 2017. Neurologically favorable survival was defined as a Cerebral Performance Category Scale of 1 or 2 at hospital discharge. Results: Of 971 public pediatric OHCA (66% male, 32% white), AEDs were used by bystanders in 117 (10.3%). AEDs were used among 2.3% of children aged ≤ 1 year (infants), 8.3% of 2-5 year-olds, 12.4% of 6-11 year-olds, and 18.2% of 12-18 year-olds (p&lt;0.001). AED use was similar among white (11.1%), black (9.1%), and Hispanic children (8.1%) (p=0.84). AED use was more common with the provision of bystander CPR (19.1%) vs no bystander CPR (0.9%), witnessed arrests (16.0%) vs unwitnessed arrests (4.7%), and arrests with a shockable rhythm (23.6%) vs a nonshockable rhythm (6.3%) (p&lt;0.001 for all). Overall, adjusted neurologically favorable survival was 29.1% (95% CI 22.7%, 35.5%) when a bystander used an AED compared to 23.7% (95% confidence interval [CI] 21.1%, 26.3%) for no bystander AED use (p=0.11). There was a significant interaction with age and race/ethnicity. AEDs were associated with neurologically favorable survival among children aged 12-18 years (p=0.04) but not associated with neurologically favorable survival in children ≤ 1 year (p=0.43), 1-5 years (p=0.16) or 6-11 years (0.41). AEDs were also associated with neurologically favorable survival in white children (p=0.01) but not with black (p=0.97) or Hispanic children (p=0.06). Conclusions: AED use is uncommon in children suffering OHCA but is associated with improved neurologically favorable survival. The benefit of AEDs was evident mostly for adolescents and white children. Further study is needed to understand these disparities in AED use and outcomes after AED use.
Endoscopy International Open – recently published
Journal: Endoscopy (2021)

Comment on: Is jumbo biopsy forceps comparable to cold snare for diminutive colorectal polyps? – a meta-analysisEndosc Int Open 2021; 09(01): E9-E13DOI: 10.1055/a-1293-6965 Comment on: Evaluation of the optical criteria for sessile serrated lesions of the colon: A prospective study on a colorectal cancer screening populationEndosc Int Open 2021; 09(01): E14-E21DOI: 10.1055/a-1293-7086 Comment on: Endoscopic resection is more effective than biopsy or EUS to detect residual rectal neuroendocrine tumorEndosc Int Open 2021; 09(01): E4-E8DOI: 10.1055/a-1300-1017
Distribution of NCCN risk classifications using MRI-ultrasound fusion versus systematic 12 core biopsies.
Authors: Ghazal Khajir, Benjamin Press, Angelique W. Levi, Preston C. Sprenkle, Michael S. Leapman
Journal: Journal of Clinical Oncology (2022)

283 Background: The widely-used National Comprehensive Cancer Network (NCCN) risk criteria for prostate cancer are impactful for patient and clinicians, particularly when assessing suitability for initial active surveillance. However, in the era of MRI-guided biopsy, fewer patients may meet stringent “very-low risk” criteria due to improved sampling, which may lead to over-treatment of non-lethal cancers. We evaluated the distribution of prostate cancer risk classification obtained using MRI-ultrasound fusion versus systematic 12 core biopsy. Methods: We performed a retrospective study of patients who underwent prostate MRI-ultrasound fusion biopsy at a single institution from January 2017 to July 2021. The primary study objective was to characterize the proportion of patients meeting NCCN “very-low risk” designation within a contemporary biopsy cohort. We calculated NCCN risk classifications (very low, low, favorable intermediate, unfavorable intermediate, high, and very high) based on constituent components (PSA, PSA density, number of biopsy cores positive, greatest extent of core positivity). We conducted comparisons within patients based on findings obtained through MRI-ultrasound fusion biopsy versus systematic biopsy only. Results: We identified 1,132 patients, including 1,014 (89.5%) and 118 (10.5%) who underwent first-time biopsy and surveillance biopsies. The median PSA was 7.15 (interquartile range: 5.2-10.8). Using data obtained through systematic biopsy alone, 123 (10.9%) and 242 (21.4%) were classified as very-low and low NCCN risk, respectively. Incorporating data from MRI-ultrasound fusion biopsy, 86 (7.6%) and 255 (22.5%) were classified as very-low and low NCCN risk, respectively. Among patients initially electing active surveillance as management, 7.4%, 60.2%, 26.9% met very-low, low, and favorable-intermediate risk criteria, respectively. Conclusions: A small proportion of patients undergoing MRI-ultrasound fusion biopsy will be classified as ‘very-low risk’ by the NCCN definition, and the majority of patients managed initially with active surveillance fall outside of this criteria. These findings imply a need to broaden support for active surveillance outside of “very-low risk” criteria to promote greater uptake.[Table: see text]
Predictive accuracy of PSA density in the UCSF-CAPRA score.
Authors: Robert Parker, Alexander Bell, Scott Greenberg, Samuel L. Washington, Janet E. Cowan, Matthew R. Cooperberg, Peter Carroll
Journal: Journal of Clinical Oncology (2022)

233 Background: The UCSF-CAPRA score is a validated risk tool that uses patient factors at diagnosis to predict prostate cancer outcomes after radical prostatectomy. This study aims to evaluate whether the substitution of prostate-specific antigen (PSA) density for serum PSA improves the predictive performance of the clinical CAPRA model. Methods: Participants were diagnosed in 2000-2019 with stage T1/T2 cancer, underwent radical prostatectomy (RP) for prostate cancer, and had at least 6 months of post-surgical follow up. We computed the standard CAPRA clinical risk score using diagnostic age, Gleason grade, percentage of positive cores, clinical T stage, and serum PSA, as well as an alternate score based on the same variables but substituting PSA density (incremental categories) for serum PSA. We reported validated CAPRA categories of low (0-2), intermediate (3-5) and high (6-10) risk. Recurrence was defined as 2 consecutive PSA &gt; = 0.2 ng/ml or receipt of salvage treatment. Life table and Kaplan-Meier analysis was used to evaluate recurrence-free survival after prostatectomy. Two Cox proportional hazards regression models were used to test associations of standard or alternate CAPRA component variables with risk of recurrence. Two additional models tested associations between standard CAPRA score or alternate CAPRA score with risk of recurrence. The Cox log-likelihood ratio test (-2 LOG L) was used to assess model accuracy. Results: A total of 2,557 patients had a median age of 61 years (IQR 56-66), GG1 34% and GG2 30%, median PSA 6.3 (IQR 4.8-9.3), and median PSA density 0.19 (IQR 0.13-0.29). Post-surgical follow up was 49 months (IQR 25-86). The alternate CAPRA model was associated with significant shifts in risk scores, with 16% of patients increasing and 6% decreasing (p &lt; 0.01). Recurrence-free survival after RP was 75% at 5 years and 63% at 10 years. Both CAPRA component models were associated with risk of recurrence after RP on Cox regression. Covariate fit statistics showed significantly better fit (low -2 LOG L) for the standard CAPRA model compared to the alternate model (-p &lt; 0.01). Both standard (HR 1.55; 95% CI 1.49-1.61) and alternate (HR 1.52; 95%CI 1.46-1.58) CAPRA scores were associated with risk of recurrence, with better fit for the standard model p &lt; 0.01). Conclusions: In a cohort of 2,557 men followed for a median of 49 months after RP, a alternate CAPRA model using PSA was associated with higher risk of BCR, but did not perform better than the standard CAPRA model at predicting BCR. While PSA density is well established as an independent prognostic variable in the pre-diagnostic setting and for sub-stratifying otherwise low-risk disease, it does not appear to improve predictive accuracy of BCR models when applied across the full range of cancer risk.
Expert Perspective: An Approach to Refractory Lupus Nephritis
Authors: Swati Arora, Brad H. Rovin
Journal: Arthritis & Rheumatology (2022)

Systemic lupus erythematosus affects the kidneys in ~50% of all patients, and lupus nephritis (LN) is the most common manifestation of kidney involvement. Despite prompt diagnosis and treatment with aggressive immunosuppression, a significant proportion of LN patients do not respond to treatment and are considered to have refractory LN. Several factors other than drug resistance, such as nonadherence to treatment, undertreatment with conventional drugs, the effects of accumulated chronic damage, and genetic factors, may contribute to a poor response to treatment and should be considered. We define refractory LN as no change in (or worsening of) proteinuria and/or estimated glomerular filtration rate in response to 2 different standard‐of‐care induction regimens after 4–6 months in patients who are adherent to treatment. For patients who have LN that is truly refractory to standard of care, B cell–targeted therapy, specifically rituximab (RTX), is the most common next step. There is limited evidence available on alternative rescue therapies that may be used when there is no response to RTX. These include anti‐CD38, leflunomide, intravenous immunoglobulin, plasma exchange, autologous stem cell transplantation, chimeric antigen receptor T cell therapy, anticomplement therapy, and interleukin‐2 therapy.
The Diabetes Prevention Program (DPP)
Journal: Diabetes Care (2002)

The purpose of the present article is to provide a detailed description of the highly successful lifestyle intervention administered to 1,079 participants, which included 45% racial and ethnic minorities and resulted in a 58% reduction in the incidence rate of diabetes (2). The two major goals of the Diabetes Prevention Program (DPP) lifestyle intervention were a minimum of 7% weight loss/weight maintenance and a minimum of 150 min of physical activity similar in intensity to brisk walking. Both goals were hypothesized to be feasible, safe, and effective based on previous clinical trials in other countries (3–7). The methods used to achieve these lifestyle goals include the following key features: 1) individual case managers or “lifestyle coaches;” 2) frequent contact with participants; 3) a structured, state-of-the-art, 16-session core-curriculum that taught behavioral self-management strategies for weight loss and physical activity; 4) supervised physical activity sessions; 5) a more flexible maintenance intervention, combining group and individual approaches, motivational campaigns, and “restarts;” 6) individualization through a “toolbox” of adherence strategies; 7) tailoring of materials and strategies to address ethnic diversity; and finally 8) an extensive network of training, feedback, and clinical support.