tbuckley/cabot-search huggingface dataset:
Predictors of objective response to first-line immuno-oncology combination therapies in metastatic renal cell carcinoma: Results from the international metastatic renal cell database consortium (IMDC).
Authors: Vishal Navani, Matthew Scott Ernst, Connor Wells, Takeshi Yuasa, Kosuke Takemura, Frede Donskov, Naveen S. Basappa, Andrew Lachlan Schmidt, Sumanta K. Pal, Luis A Meza, Lori Wood, D. Scott Ernst, Bernadett Szabados, Rana R. McKay, Andrew James Weickhardt, Cristina Suárez, Anil Kapoor, Jae-Lyun Lee, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2022)

310 Background: Predictors of objective response to first-line (1L) immuno-oncology (IO) combination therapies remain elusive. We sought to characterise clinical variables and their association with investigator assessed best overall response. Methods: Using the IMDC, we retrospectively identified patients treated with 1L ipilimumab nivolumab (IPI-NIVO) or approved IO/vascular endothelial growth factor (VEGF) inhibitor combinations (IOVE). Patients were classified, per RECIST v1.1, as responders (complete or partial response (CR or PR)) or non-responders (stable or progressive disease (SD or PD)). Logistic regression was used to adjust for IMDC criteria. Results: Out of 1084 patients, 794 (73%) received IPI-NIVO and 290 (27%) received IOVE (axitinib+pembrolizumab, cabozantinib+nivolumab, axitinib+avelumab, lenvatinib+pembrolizumab). Favourable, intermediate and poor IMDC risk comprised 147 (16%), 517 (55%) and 272 (29%) respectively. Of the 898 patients with evaluable responses, 37 (4%) achieved a best response of CR, 343 (38%) PR, 315 (35%) SD and 203 (23%) PD. Corresponding median overall survival from time of 1L initiation was: not reached, 55.9, 48.1, and 13 months respectively (logrank p &lt; 0.0001). In a multivariable model, lung metastases and cytoreductive nephrectomy (CN) (performed after diagnosis of metastatic disease and before 1L therapy) retained independent association with response, after adjustment for IMDC criteria. Factors not associated with response included (with univariable p values): gender (p = 0.58), age (p = 0.06), sarcomatoid histology (p = 0.99), smoking status (p = 0.39), liver (p = 0.63) and brain (p = 0.12) metastases. As in the VEGF monotherapy era, improved IMDC prognostic risk was associated with response. Results were similar when restricted to the IPI-NIVO cohort. Conclusions: Presence of lung metastases, CN and better IMDC risk group are associated with a higher probability of response to 1L immunotherapy combination regimens. Further work to identify reliable predictors of response to guide treatment selection and patient counselling is warranted.[Table: see text]
Notes and Observations on Diseases of the Heart and Lungs
Authors: T. Shapter
Journal: BMJ (1868)

THE BRITISH MEDICAL 7OURNAL.-ishort, spare, and somewhat delicate in appearance, was employed in a cap-manufactory, in a department which was not trying to the sight.Her general health was said to be good.A fortnight before I saw her, she first noticed dimness of the left eye, which continued ever since, but was said to vary in degree.On the morning of Dec. igth, she observed the appearance as of a star before this eye in rapid rotatory motion, which had not been seen before.The right eye was healthy.Examined with the ophthalmoscope, the pupil partially dilated, a filmy minute globular opacity was distinguishable in patches, obscuring the view of the disc, and rendering vision dim, especially of objects situated beneath the level of the pupil.This patient was also put upon a tonic plan of treatment--cinchona, with the liquor hydrargyri bichloridi; also an oc- casional alterative pill, and the cold affusion, as in the former case.She very soon began to improve in sight; and on January 27th, i868, -when examined with the ophthalmoscope, the opacity was found to have entirely disappeared, the disc was distinctly visible, and vision was stated to be as good as ever.The next two cases may be briefly disposed of, as I cannot speak as to the result of the treatment employed.CASE iii.-MayI867.Mrs. R., aged 26, about medium height, pale complexion, dark hair, and feeble aspect, said that she felt weak, and had suffered a good deal of mental anxiety.Her father died of consumption when she was an infant.Her sight had been failing for several months past, and all objects appeared as if seen through a smoky medium.Vision with the left eye (which, I presume, was the only one affected, although it is not stated in my notes) was so defective that she could not distinguish my features.Examined with the ophthalmoscope, the pupil dilated, the disc was distinctly 'visible through a fine gauzy film, which presented the appearance as of dust sprinkled upon a transparent surface.At the inner side of the disc, close to the base, there was a small linear-shaped black opacity.For this patient I prescribed the citrate of iron and quinine, three grains thrice daily, and good diet, with some wine; rest of the eyes, especially at night; avoid- ance of fatigue; and the use of blue tinted glasses.As I did not see her again, I hope the means employed were beneficial.CASE Iv.-Nov.i866.Henry Reid, aged 33, engineer, and married, of medium height, moderately stout, light hair and eyes, rather feeble aspect, said that he had fever in Calcutta four years ago, and was ill for about two months, but did not think that his sight was affected after he recovered.However, he had never felt so well since.A little extra
Testing drug release from medicated contact lenses: The missing link to predict in vivo performance
Authors: Ana F. Pereira-da-Mota, Chau-Minh Phan, Angel Concheiro, Lyndon Jones, Carmen Alvarez-Lorenzo
Journal: Journal of Controlled Release (2022)

Contact lenses (CLs) offer a wide variety of advantages as ocular drug-releasing platforms, but the feasibility of medicated CL development is constrained by numerous scientific, technological, and regulatory challenges. One main difficulty is the setting of release rate specifications for each drug, since at present there are no standardized in vitro release models that can appropriately predict the performance of drug-eluting CLs once placed onto the eye. CL-adapted release tests may provide knowledge on how the drug release pattern should perform in vivo to trigger and maintain the therapeutic effects for both anterior and posterior ocular tissues. Moreover, in vitro release tests are valuable tools for quality assessment during production and to investigate the effect of a change in composition or process variables. This review aims to shed light on biorelevant ways of evaluating in vitro drug release from CLs and the feasibility of establishing in vitro-in vivo correlations (IVIVC) to predict in vivo performance. First, general guidelines and Pharmacopeia release tests for topical ophthalmic formulations as well as in vitro release tests implemented for drug-CLs in the last two decades are analyzed. Then, development of an appropriate method to investigate IVIVC is attempted from the few papers simultaneously reporting in vitro release profiles and either in vivo release or therapeutic response. Finally, key points to be considered for in vitro testing drug release from a medicated CL are suggested to pave the way to the clinical arena.
LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson's disease
Authors: Eunice Eun Seo Chang, Philip Wing-Lok Ho, Hui-Fang Liu, Shirley Yin-Yu Pang, Chi-Ting Leung, Yasine Malki, Zoe Yuen-Kiu Choi, David Boyer Ramsden, Shu-Leong Ho
Journal: Translational Neurodegeneration (2022)

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are one of the most frequent genetic causes of both familial and sporadic Parkinson's disease (PD). Mounting evidence has demonstrated pathological similarities between LRRK2-associated PD (LRRK2-PD) and sporadic PD, suggesting that LRRK2 is a potential disease modulator and a therapeutic target in PD. LRRK2 mutant knock-in (KI) mouse models display subtle alterations in pathological aspects that mirror early-stage PD, including increased susceptibility of nigrostriatal neurotransmission, development of motor and non-motor symptoms, mitochondrial and autophagy-lysosomal defects and synucleinopathies. This review provides a rationale for the use of LRRK2 KI mice to investigate the LRRK2-mediated pathogenesis of PD and implications from current findings from different LRRK2 KI mouse models, and ultimately discusses the therapeutic potentials against LRRK2-associated pathologies in PD.
Highlights
Journal: JAMA Surgery (2019)

Diverting Ileostomy for Clostridium difficile Colitis 899Diverting ileostomy has been proposed as a less morbid alternative to subtotal colectomy for the surgical treatment of fulminant Clostridium difficile colitis.Juo and colleagues evaluated the trend in diverting ileostomy usage from 2011 to 2015 in a National Inpatient Sample data set.They found that the proportion of patients with fulminant C difficile colitis receiving diverting ileostomy without subtotal colectomy increased from 11.2% to 25.3%, with no significant difference in outcomes between loop ileostomy and total abdominal colectomy.
Incorrect Numbers in Table in: Fluorouracil vs Gemcitabine Chemotherapy Before and After Fluorouracil-Based Chemoradiation Following Resection of Pancreatic Adenocarcinoma: A Randomized Controlled Trial
Journal: JAMA (2008)

In Reply: In response to the comments by Drs Racine and Joyce, I recommend Beauchamp's trenchant assessment of market justice in his article "Public Health as Social Justice," 1 published more than 30 years ago.That this article remains pertinent today highlights the continuing effects of market justice on health and health care in our society.His rejoinder to critics of the use of the term market justice follows:Some might object strenuously to the marriage of the two terms 'market' and 'justice.'One theory of the market holds that it is a blind hand that rewards without regard to merit or individual effort.For this point of view, see: [Friedman 2 and Hayek 3 ] . . .But Irving Kristol 4 . . .argues that this is a minority view; most accept the marriage of the market ideal and the merits of individual effort and performance.I agree with this point of view-which is to say I see the dominant model of justice in America as a merger of the notions of meritarian and market norms.
Abstract 16116: Genetic Deficiency of the H2S Producing Enzyme, Cystathionine Gamma-Lyase (CSE) Results in Impaired Cardiac Mitochondrial Function, Increased Oxidative Stress, and Exacerbated Myocardial Reperfusion Injury
Authors: Adrienne L King, Shashi Bushan, Benjamin Predmore, Marah Condit, Juan Pablo Aragon, Rui Wang, David J Lefer
Journal: Circulation (2011)

Introduction: H2S is formed from cysteine by enzymes in the mammalian heart via cystathionine γ-lyase (CSE). H2S is a critical gaseous signaling molecule that upregulates antioxidants and promotes ...
Premature and Congenitally Diseased Infants.
Journal: JAMA (1923)

Medicine has become so enormous in its scope and its facts, and hypotheses concerning disease have accumulated to such an extent that the abbreviations necessary in the general textbooks fall short of the necessary knowledge of the diseases of which these textbooks treat. It is becoming increasingly necessary, therefore, to consult monographs to obtain an adequate idea of any subject in which one may be interested. It is to meet just such a need that this volume appears. It is the only book in English, and the only book of any claim to prominence, if, indeed, it is not the only book that has ever appeared on the subject. In view of the absence of background, it is surising that the writer should have assembled and systematized his facts so well. The book is well written and beautifully illustrated; what is more, the illustrations are to the point. The literature
An Extracellular Matrix‐Liposome Composite, a Novel Extracellular Matrix Delivery System for Accelerated Tissue Regeneration (Adv. Healthcare Mater. 4/2022)
Authors: Keel Yong Lee, Huong Thanh Nguyen, Agustina Setiawati, So‐Jung Nam, Minyoung Kim, Il‐Gyu Ko, Won Hee Jung, Kevin K. Parker, Chang‐Ju Kim, Kwanwoo Shin
Journal: Advanced Healthcare Materials (2022)

Wound Healing A new platform for the delivery of extracellular matrix (ECM) that can rapidly heal damaged tissues is developed. In article number 2101599, Kevin K. Parker, Chang-Ju Kim, Kwanwoo Shin, and co-workers, confirm that when unfolded fibronectins are delivered by binding to small unilamellar vesicles with negative charges, they are very effective in tissue regeneration. Their findings suggest that it could be a novel ECM delivery system for ECM-based therapeutic applications, including the treatment of ulcerative colitis and inflammatory bowel disease.
Kernicterus in Full-Term Infants--United States, 1994-1998
Journal: JAMA (2001)

Kernicterus is a preventable life-long neurologic syndrome caused by severe and untreated hyperbilirubinemia during the neonatal period. High levels of bilirubin are toxic to the developing newborn. In full-term infants, hyperbilirubinemia symptoms include severe jaundice, lethargy, and poorfeeding. Features of kernicterus may include choreoathetoid cerebral palsy, mental retardation, sensorineural hearing loss, and gaze paresis. Kernicterus is not a reportable condition in the United States, and its prevalence is unknown; however, a pilot registry at a Pennsylvania hospital documented 90 cases in 21 states from 1984 to June 2001 (L. Johnson, Pennsylvania Hospital, Philadelphia, personal communication, 2001). This report summarizes case histories of four full-term, healthy infants who developed kernicterus and underscores that to prevent kernicterus, newborns must be screened and promptly treated for hyperbilirubinemia.
Discordance of patient- and physician-reported toxicities in two prospective trials of stereotactic body radiotherapy (SBRT) for localized prostate cancer.
Authors: Akshat Patel, Rohit R Badia, Armon Amini, Christopher Kung, Samuel B. Kusin, Sarah Neufeld, Samantha Mannala, Aurelie Garant, Raquibul Hannan, Robert D. Timmerman, Michael J. Zelefsky, Michael Ryan Folkert, Neil Bipinchandra Desai
Journal: Journal of Clinical Oncology (2022)

245 Background: SBRT for localized prostate cancer (PCa) is the focus of several ongoing and reported high-impact trials, which often focus on physician-reported toxicity (P-Tox) when comparing regimens. Patient-reported quality of life (PR-QoL) may differ and provide a more sensitive comparative metric of treatment burden, especially with fewer provider interactions during SBRT than during protracted RT courses. We evaluated the concordance of prospective genitourinary (GU) and gastrointestinal (GI) P-Tox and PR-QOL in men receiving SBRT for PCa. Methods: Data from two concurrently-enrolled prospective trials of SBRT in high-risk (Phase I Safety Endpoint, NCT01896271) and low-intermediate risk (Phase II GI Toxicity Endpoint, NCT02353832) PCa were used. Matching standardized schedules of collected PR-QoL [Expanded Prostate Cancer Index Composite (EPIC)] and P-Tox (CTCAE v5.0) were analyzed over the first 18 months of follow up, where symptoms are most pronounced. We assessed concordance of Grade≥2 GU/GI physician reported toxicity with PR-QoL declines exceeding anchor based minimal clinically important difference (MCID) thresholds (-6 urinary and -5 bowel summary scores, respectively) for each patient at each time point. Patients without baseline PR-QoL data were excluded in full, while time points with missing PR-QoL or P-Tox were excluded individually without imputation. Concordance was evaluated by Cohen’s kappa statistic. Results: From 101 patients, there were 256 (64%) follow up observations through 18 months with both PR-QoL and P-Tox at the time point and baseline. Concordance of PR-QoL and P-Tox was low at all time points for both GU and GI toxicity domains (mean kappa 0.093; Table). MCID was more often reported by patients than Grade≥2 toxicity by physicians (38% vs 17% for GU and 44% vs 10% for GI). There was little overlap of PR-QoL and P-Tox reporting: Grade≥2 P-Tox reported in 17% of observations with MCID in PR-QoL, while MCID in PR-QoL reported in 54% of observations of Grade ≥2 P-Tox. Mean concordance was similarly low when analyzing sub-groups of trial, investigator, and an alternative 2xMCID threshold. Conclusions: P-Tox and PR-QoL differed dramatically in two prospective studies of SBRT despite toxicity primary endpoints. This may reflect subjective and varying intervention thresholds driving P-Tox reporting, rather than actual patient burden. These data strongly support use of PR-QoL rather than P-Tox for SBRT comparative study endpoints and guidelines in this rapidly evolving space. [Table: see text]
Acute kidney disease is common and associated with poor outcomes in patients with cirrhosis and acute kidney injury
Authors: Kavish R Patidar, Mobasshir A Naved, Ananth Grama, Mohammad Adibuzzaman, Arzina Aziz Ali, James E Slaven, Archita P Desai, Marwan S Ghabril, Lauren Nephew, Naga Chalasani, Eric S Orman
Journal: Journal of Hepatology (2022)
Laurel V. Schaubert: the value of visuals
Authors: G. McBride
Journal: JAMA (1980)

"There.<i>That's</i>what I mean by visual static," says Laurel Schaubert, leafing through a medical journal. "No one can possibly take in all the material in that graph without studying it for about a half hour. "Visual static is something that interrupts the message," she explains, "because you have to stop and figure out what the illustration is trying to say. You find it in so many medical journals. "Now if those authors had just come to us...." She laughs. "Or if the journal even had an art director." Laurel Schaubert is hardly satisfied with the state of medical illustration in most medical and scientific journals. The same goes for many oral presentations accompanied by slides. As for books and pamphlets, they vary. Some are dismal and confusing in terms of illustrations. Others are clearer and more vivid because of them. A certain line of soft-cover medical books, for example,
Abstract 17178: Adverse Events in Endovascular Robotic Assisted Procedures
Authors: Naveen Kumar Sankaran, Sai Rakesh Rachakonda, Abraham Kocheril, Suraj Kapa, Thenkurussi Kesavadas
Journal: Circulation (2018)

Introduction: Endovascular procedures are traditionally performed for a variety of indications. However, guidewire/catheter manipulation and hazardous radiation exposure are limitations to manual interventions. Thus, significant work has been done to develop robotic approaches to therapies. These devices have FDA clearance for performing procedures like cardiac arrhythmias, angioplasty, aneurysm repair and stenting etc. With the increasing usage of robotic assistance in endovascular procedures, it is essential to understand the adverse events that may occur. This study aims to provide an understanding of adverse events with currently available robotic systems. Methods: The analysis of adverse events is performed with the FDA MAUDE (Manufacturer and User Facility Device Experience) database. MAUDE database is a collection of reports on medical devices reported by manufacturers, distributors, users, volunteers. In case of occurrence of adverse events, FDA regulations requires that event to be reported for further investigation. Based on the impact of events on the patient’s outcome, the reported events were grouped into 3 categories death (patient death), injury (patient injury) or device malfunction. Results: A total of 71 different events were reported collectively for all the four robotic devices (Hansen Medical- 37, Corindus Inc.-27, Stereotaxis Inc.-5 &amp; Catheter Robotics Inc.-2). The major adverse events included death and common injuries such as perforation, pseudo-aneurysm / blockage/ tamponade/ clot, blood pressure dropped or an effusion, or hemodynamic instability. The table summarizes the events by brand of system. Conclusions: While robotic approaches to intervention reflect a potentially useful means to improve outcomes of endovascular procedures by optimizing catheter manipulation with finer robotic motions or limiting radiation exposure, there are potentially significant risks. Whether these reflect higher or lower risk than traditional manual approaches requires randomized studies. Use of robotic technologies may present additional risks in light of potential malfunctions that occur from system errors that a human system may not be prone to. Future studies will be needed to better understand incremental benefit.
High amounts of SARS-CoV-2 in aerosols exhaled by patients with Omicron variant infection
Authors: Jing Zheng, Zhongyi Wang, Jiaming Li, Yidun Zhang, Lina Jiang, Yingying Fu, Yifei Jin, Hongliang Cheng, Jingjing Li, Zehui Chen, Fei Tang, Bing Lu, Li Li, Xiaopeng Zhang
Journal: Journal of Infection (2022)
Pharmacology of Nicotine: Addiction and Therapeutics
Authors: N. L. Benowitz
Journal: The Annual Review of Pharmacology and Toxicology (1996)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
General Remarks on the Practice of Medicine
Authors: P. M. Latham
Journal: BMJ (1861)

Treatment distinct from Cure.Conversant not im- mnediately wcitlh the Disease, but with intermediate Purposes.TW/hat is meant by Indications of Treat- ment.Chiosen from present Symptoms.Not ne- cessarily the most Prominent Symptoms.Or nearest akin to the particular Disease patholoqically.Often common alike to manty Diseases.And the Largest and most comprehensive.WE come now to consider Treatment as distin- guished from Cue. Treatment seeks to abolish the disease after fulfilling one or several primary and intermediate purposes aimed at and intended by the physician.These intermediate purposes are called Indications of Treatment.They are, upon the whole, of much variety, and in each particular case may be a single one, or few, or many; and, accordingly, the means or remedies by which indications are sought to be fulfilled are various upon the whole, and in each particular case may be a single one, or few, or many.
Postoperative pain.
Authors: E N Fry
Journal: BMJ (1976)

of ours who is in long-term remission after chemotherapy of acute myeloblastic leukaemia in childhood.He is now married and has two normal children.In September 1963, when aged 9 years, he was found to have acute myeloblastic leukaemia, was treated with prednisone and 6-mercaptopurine, and went into remission.He relapsed in January 1965 and was then treated with prednisone and methotrexate, achieving a further but short remission and relapsing in July 1965.This second relapse was treated with prednisolone and cyclo- phosphamide and was followed by complete clinical and haematological remission which has been maintained ever since.Treatment was stopped at the end of 1967.The patient married in 1972 and has a daughter aged 4 and a son aged 2 years, both clinically well.He was last seen (with his family) in June 1976 and found to be in continued haematological remission.Between her two normal pregnancies his wife had a miscarriage, but nothing is known about the condition of the fetus.