tbuckley/cabot-search huggingface dataset:
Early changes in peripheral blood neutrophil-lymphocyte ratio (NLR) to predict outcomes with immune checkpoint inhibitors (ICIs) for metastatic urothelial carcinoma (mUC).
Authors: Jonathan Thomas, Irbaz Bin Riaz, Dory Freeman, Elio Adib, Pier Vitale Nuzzo, Talal El Zarif, Matthew Davidsohn, Heather McClure, Catherine Curran, Praful Ravi, Ritu Yadav, Uttam Kalluri, Jana Zeineddine, Ayah Matar, Bradley Alexander McGregor, Charlene Mantia, Guru P. Sonpavde
Journal: Journal of Clinical Oncology (2022)

449 Background: ICIs have provided advances in the therapy of mUC. However, the objective determination of benefit from ICIs determined by radiographic imaging may take months and may be confounded by pseudoprogression. Peripheral blood cells appear to reflect tumor microenvironment immune infiltrating cells. Given the known prognostic impact of baseline peripheral blood NLR, we aimed to investigate dynamic early changes in NLR as a biomarker of benefit in patients (pts) with mUC. Methods: Deidentified data from mUC pts who were treated with ICIs at Dana Farber Cancer Institute from 2015 to 2020 were reviewed retrospectively. Demographic data (age, gender), setting (untreated vs. post-platinum), sites of metastasis, performance status (PS), platelet count, and NLR at baseline and 3-4 weeks after initiating the ICI were collected. We assessed the association of NLR at baseline and 3-4 weeks after starting the ICI with any regression of tumor (ART) and overall survival (OS). A multivariable logistic regression model and Cox proportional-hazards model was employed to identify the association of NLR changes with ART and OS, respectively, using backward selection. Results: A total of 144 pts were included. The median age was 76 years and 100 (69.3%) were male. Overall, 54.8% (n=79) had ART and the median OS was 15.2 (12.2-23.5) months. 37.5% (n=54) were platinum naive and the remaining received post-platinum ICI therapy. In the multivariable models (Table), an increase in NLR, defined as an increase in NLR by ≥1.0 from baseline at 3-4 weeks was significantly associated with lower odds of ART (Odds Ratio (OR)= 0.80; 95% CI = 0.70-0.90; p = 0.0004) and worse OS (HR = 1.08; 95% CI = 1.05-1.11; p &lt; 0.0001). The presence of liver metastasis was associated with lower odds of ART (OR = 0.30; 95% CI = 0.13-0.70; p = 0.006) and OS (HR 2.73; 95% CI 1.71 - 4.36; p&lt;0.0001). Conclusions: Change in NLR in the first 4 weeks after initiating ICI for mUC was associated with tumor regression and survival in pts with mUC. Change in NLR may assist in early identification of benefit as well as identification of pts who may have progression of disease. Further validation is warranted to facilitate the early discrimination of benefit from ICIs in pts with mUC.[Table: see text]
Effects of COVID-19 protective face masks and wearing durations on respiratory haemodynamic physiology and exhaled breath constituents
Authors: Pritam Sukul, Julia Bartels, Patricia Fuchs, Phillip Trefz, Rasmus Remy, Leo Rührmund, Svend Kamysek, Jochen K. Schubert, Wolfram Miekisch
Journal: European Respiratory Journal (2022)

Background While assumed to protect against coronavirus transmission, face masks may have effects on respiratory–haemodynamic parameters. Within this pilot study, we investigated immediate and progressive effects of FFP2 and surgical masks on exhaled breath constituents and physiological attributes in 30 adults at rest. Methods We continuously monitored exhaled breath profiles within mask space in older (age 60–80 years) and young to middle-aged (age 20–59 years) adults over the period of 15 and 30 min by high-resolution real-time mass-spectrometry. Peripheral oxygen saturation ( S pO 2 ) and respiratory and haemodynamic parameters were measured (noninvasively) simultaneously. Results Profound, consistent and significant (p≤0.001) changes in S pO 2 (≥60_FFP2-15 min: 5.8±1.3%↓, ≥60_surgical-15 min: 3.6±0.9%↓, &lt;60_FFP2-30 min: 1.9±1.0%↓, &lt;60_surgical-30 min: 0.9±0.6%↓) and end-tidal carbon dioxide tension ( P ETCO 2 ) (≥60_FFP2-15 min: 19.1±8.0%↑, ≥60_surgical-15 min: 11.6±7.6%↑, &lt;60_FFP2- 30 min: 12.1±4.5%↑, &lt;60_surgical- 30 min: 9.3±4.1%↑) indicate ascending deoxygenation and hypercarbia. Secondary changes (p≤0.005) to haemodynamic parameters ( e.g. mean arterial pressure (MAP) ≥60_FFP2-15 min: 9.8±10.4%↑) were found. Exhalation of bloodborne volatile metabolites, e.g. aldehydes, hemiterpene, organosulfur, short-chain fatty acids, alcohols, ketone, aromatics, nitrile and monoterpene mirrored behaviour of cardiac output, MAP, S pO 2 , respiratory rate and P ETCO 2 . Exhaled humidity ( e.g. ≥60_FFP2-15 min: 7.1±5.8%↑) and exhaled oxygen ( e.g. ≥60_FFP2-15 min: 6.1±10.0%↓) changed significantly (p≤0.005) over time. Conclusions Breathomics allows unique physiometabolic insights into immediate and transient effects of face mask wearing. Physiological parameters and breath profiles of endogenous and/or exogenous volatile metabolites indicated putative cross-talk between transient hypoxaemia, oxidative stress, hypercarbia, vasoconstriction, altered systemic microbial activity, energy homeostasis, compartmental storage and washout. FFP2 masks had a more pronounced effect than surgical masks. Older adults were more vulnerable to FFP2 mask-induced hypercarbia, arterial oxygen decline, blood pressure fluctuations and concomitant physiological and metabolic effects.
Dynamic coupling of oscillatory neural activity and its roles in visual attention
Authors: Moein Esghaei, Stefan Treue, Trichur R. Vidyasagar
Journal: Trends in Neurosciences (2022)

Oscillatory neural activity is believed to have a central role in information processing in the mammalian brain. While early studies often focussed on the function of individual frequency bands, there is emerging appreciation for the role of simultaneous activity in many distinct frequency bands and the interactions between them in high-level cognitive functions. Here, we focus on the role of cross-frequency coupling (CFC) in visual attention. First, we propose a framework that reconciles previous contrasting findings, showing how CFC could have a functional role on both intra- and interareal scales. Second, we outline how CFC between distinct frequency bands could label different submodalities of sensory information. Overall, our scheme provides a novel perspective of how interfrequency interaction contributes to efficient and dynamic processing of information across the brain.
PHLYCTENULAR KERATITIS.
Authors: DUDLEY S. REYNOLDS
Journal: JAMA (1898)

At the meeting of theAmerican Medical Associationin 1893, I had the honor to introduce the subject of phlyctenular ophthalmia. My paper elicited extended discussion, embracing many divergent views both as to etiology and treatment. The result of that discussion determined in my mind the necessity of more painstaking observations. For reasons beyond my control, I was not able to begin my work until August, 1894, and I am now indebted to the painstaking labor of my friend, Dr. Travis A. Bullington, for the first part of what I intend to be a continuous series of observations concerning the nature, causes, and the treatment of phlyctenular ophthalmia. The first series of observations by Dr. Bullington, and which I have the honor now to present for your consideration, is taken from my clinical record at the Hospital College of Medicine, beginning August 25, 1894, and extending through the first one
BLACKWATER FEVER
Authors: R. U. Moffat
Journal: BMJ (1902)

JORNAL _ 95 cases were also at first taken for leprosy.Ehlers5 and Neu mann,6 who investigated the matter, found it was not leprosy' but the symmetrical affection aforementioned.That such a confusion should have existed is another proof of the view that a variety of skin affections were in years gone by included under leprosy: But that is another story.Leprosy-that is, leprous nodules and infiltrations of the soles and palms-is rare, and, involving the latter areasalone, unheard of.Rille7 has recently described leprous lesions of the soles, but the patient suffered from nodular leprosy elsewhere (face, limbs) before the soles became involved.
PROGRAM SCHEDULE & Abstracts Presented at the Society of Nuclear Medicine 23rd Annual Southeastern Chapter Meeting
Authors: None &NA;
Journal: Clinical Nuclear Medicine (1982)

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Corrigenda
Journal: BMJ (1942)

OURNALThe prevalence of scabies has been a matter of great concern to local health authorities during the year.Although no com- parable figures are available, there appears to have been a large general increase in the incidence.Notifications of infectious diseases are the only data available for the whole country, but additional facts are published for the 126 great towns, which comprise roughly one-half of the population of the country.The war has seriously-disturbed the populations of these towns, and a comparison must be confined to the past two years.
Cardiac Pharmacology
Authors: Samuel Zoneraich
Journal: JAMA (1982)

Wilkerson's<i>Cardiac Pharmacology</i>couples a fine description of basic cardiovascular pharmacology and physiology with a competent presentation of clinical aspects of cardiovascular diseases. The text concerns four major points: (1) intrinsic and neural control of cardiac function; (2) pharmacologic modification of cardiac function; (3) genesis and control of cardiac arrhythmias; and (4) pharmacologic modification of myocardial oxygen supply and demand. The first section begins with the basics of myocardial contractility followed by a chapter on the role of the CNS as a "locus" for action of the drugs that influence cardiovascular function. The chapters in the following three sections tend to be extremely successful in providing informative discussion of basic principles and in supplying practical "how-to" information. The chapter on evaluation of drug-induced alteration in myocardial contractility is a good review. The subject material on the physiological and pharmacologic basis for the use of vasodilators in heart failure (chapter 8)
Letter: IPPB
Authors: Louis Tuft
Journal: JAMA (1975)

<h3>To the Editor. —</h3> Drs Barach and Segal are to be commended for their recent excellent article (231:1141,1975) alerting physicians to the indiscriminate use of the intermittent positive pressure breathing (IPPB) machine for pulmonary conditions, such as acute asthma, that could be relieved by simpler and less expensive methods. An additional drawback to use of the IPPB machine, and one that warrants emphasis, is the fact that some patients with recurrent asthma, who have been indoctrinated by its use during a hospital stay to relieve their asthma, have purchased this apparatus for use at home and have become so dependent upon it that it often is difficult to wean them away from what has now become their crutch. They use this apparatus instead of a bronchodilator tablet or a hand nebulizer to relieve the slightest breathing disturbance, regardless of whether it is associated with actual wheezing or, as I have
Notes on the Pathology and Treatment of Cholera
Authors: G. Johnson
Journal: BMJ (1866)

BritiA '3t'iE ] i.A~3ONOtO~'~& Ag~1286 on.pressur.Jn in"t c,ases, th um r fpJ coour, more eApeci'411y io -the, anterio~,,an4ipe ~~.}LL t~parts; and if the e~~~~rn.na#ion,of.'thehoW be ma4e ~TIi~~~immetdialely after death, 'the pale colour may exten throughou4 the whole.lng.IJ1* nmst-instalce4, t~r PATHOLOGY' AND 'TREATMENT is more or less engorgement. of the back:parts et OF CHOLERA.~~~~~lungs, owingtO 1pos Mwrtops graviitation.benp OF'' CHOLERkThe. anmuaia lupg ~~~has, geneT.41IybeBY ~~~~~~served to.be greatest in the most rapidl fata caIs
Screening for breast cancer.
Authors: W D George, E N Gleave, P C England, M C Wilson, R A Sellwood, D Asbury, G Hartley, P G Barker, P Hobbs, J Wakefield
Journal: BMJ (1976)

The feasibility of mass population screening for breast cancer by clinical examination and x-ray mammography was studied. The results indicate that such a programme could be conducted effectively by non-medical staff and be safe from the dangers of irradiation. The response rate of women invited for screening suggests that such a service is acceptable to the general public. The additional work load produced by screening would not overburden the existing surgical services.
Tetanus.
Authors: J Macrae
Journal: BMJ (1973)

1934-9-14 cases (10 deaths).Treated with equine antitoxin, sedatives, good nursing and, usually, general ward care.1940-6-War service.No service case since all had received active immunization by toxoid.I saw an unknown number of mostly Arab babies; it was quite impossible to persuade the mothers not to use cow dung umbilical dressings.1947-57-10 cases (6 deaths)-three had tracheostomies but all of these were seen before 1954.1958-72-153 cases (31 deaths) some received antitoxin, now largely discontinued.Assessed by Cole's dicta; each treated as an individual
LOW INCIDENCE OF STENT THROMBOSIS IN ASIAN RACES: MULTICENTER REGISTRY IN ASIA 6 YEARS FOLLOW-UP RESULT
Authors: Sunao Nakamura, Hisao Ogawa, Jang-Ho Bae, Yeo H. Cahyadi, Wasan Udayachalerm, Damras Tresukosol, Sudaratana Tansuphaswadikul
Journal: Journal of the American College of Cardiology (2011)
Deaths under 50. Medical Services Study Group of the Royal College of Physicians of London.
Journal: BMJ (1978)

The Medical Services Study Group has started a collaborative study in the Mersey, West Midlands, and Grampian regions to examine the causes of death among medical inpatients aged 1 to 50. The cause of death is determined from the case notes and the consultant's opinion. The rate of ascertainment of cases was initially low, though it is increasing; despite this limitation an analysis of the first 250 cases showed one important finding. No fewer than 98 patients contributed to their own deaths through overeating, drinking, smoking, or not complying with treatment. Despite the present statistical limitations of the study, it has been valuable in enlisting the good will of the participating physicians, which will help to ensure the success of other projects, and it has avoided the problems inherent in determining the cause of death from death certificates alone.
Lymphography.
Authors: W F White
Journal: Thorax (1970)

Much less is known of the lymphatics of the pleura and chest wall.There are two main directions of lymph flow-forwards to the internal mammary chain of nodes and vessels, and backwards to the posterior mediastinum.Some of the lymphatics of the lower intercostal spaces drain downwards, through the diaphragm, to reach the cisterna chyli.Some of the mediastinal lymphatics communicate directly with the thoracic duct while the majority run upwards to join the paratracheal and pulmonary lymphatics and then drain by one or more vessels into the veins at the base of the neck near the thoracic duct.The radiological appearances of the abnormal lymphatics in lymphangitis carcinomatosa, pulmonary oedema, etc., are discussed.Lymphography W. F. WHITE The lymphatics and lymph nodes draining many parts of the body may now be demonstrated by lymphography.
EIGHTEEN YEARS OF THE FONTAN OPERATION AT A SINGLE INSTITUTION: RESULTS FROM 771 CONSECUTIVE PATIENTS
Authors: Lindsay Rogers, Andrew C. Glatz, Chitra Ravishankar, Christina Hayden Rush, Susan C. Nicolson, Jack Rychik, Thomas L. Spray, J. William Gaynor, David J. Goldberg
Journal: Journal of the American College of Cardiology (2011)
Disseminated aspergillosis
Authors: B. J. Burke, F. K. Storring, T. E. Parry
Journal: Thorax (1970)

The history and the clinical and necropsy findings are presented of a patient who died from <i>Aspergillus fumigatus</i> pyaemia occurring as an opportunistic infection complicating a dissecting aortic aneurysm. The diagnosis was made (and treatment instituted) during life: it rested upon repeated isolation of the organism from tracheal aspirations, a positive blood culture and positive serum precipitin reactions to <i>A. fumigatus.</i> Debilitating disease along with large doses of antibiotics and corticosteroids provided the conditions necessary for the normally saphrophytic fungi to become pathogenic. As the therapy for aspergillosis is still ineffective, the danger of prescribing large doses of antibiotics together with corticosteroids is stressed.
Safety lead-in of phase II SBRT and durvalumab with or without tremelimumab for unresectable and cisplatin-ineligible, locally advanced or metastatic bladder cancer.
Authors: Palak Kundu, Alan Lee, Alexandra Drakaki, Sandy Liu, John Shen, Arnold I. Chin, Karim Chamie, Albert Chang
Journal: Journal of Clinical Oncology (2022)

517 Background: Many patients with muscle-invasive bladder cancer are not ideal candidates for chemotherapy or radical cystectomy. Moreover, local progression may further impair quality of life. Bladder preservation with maximal transurethral resection of bladder tumor (TURBT) and stereotactic body radiotherapy (SBRT) is a viable treatment option for such patients, offering durable local control while potentiating the effect of immunotherapy. Herein, we report on the safety profile of SBRT in combination with durvalumab (anti-PDL1) and tremelimumab (anti-CTLA4) in the safety lead-in cohort of an institutional Phase II trial for cisplatin-ineligible, unresectable locally advanced or metastatic bladder cancer patients. Methods: Patients with locally advanced or metastatic urothelial carcinoma, who were unwilling or unable to undergo radical cystectomy and/or systemic chemotherapy were eligible. Patients received maximal TURBT, followed by durvalumab 1500mg IV every 4 weeks and bladder SBRT 33Gy in 5 fractions between the first 2 cycles. After 6 such patients did not experience a dose limiting toxicity, tremelimumab 75mg IV was added for cycles 1-2. Patients were followed with CT Chest/Abdomen/Pelvis and cystoscopy every 3 months. Treatment-related adverse events (TRAEs) were assessed per CTCAE 5.0 and progression was assessed per RECIST 1.1. Results: Between January 2019 and May 2020, 10 patients received TURBT followed by SBRT and durvalumab (Age 73-96, 3 Female, 7 ECOG 1, 3 ECOG 0). Five patients had localized disease and 5 had nodal or distant metastases. Median cycles of durvalumab was 12.5 (2-13), and 4 patients received 2 cycles of tremelimumab. At a median follow-up of 16.8mo (6.4-30mo), there were 2 Grade 3+ immunotherapy-related TRAEs (1 Grade 3 lipase elevation self-resolved, 2 Grade 3 myositis treated with steroids). The most common TRAEs of any grade included pancreatic enzyme elevation (3 patients), rash (3 patients), and urinary symptoms related to RT (3 patients). Disease control rate 70% and local control was 90%. There were 3 non-treatment related deaths. Conclusions: Bladder SBRT with durvalumab and tremelimumab was well tolerated and demonstrated promising local control in the safety lead-in cohort. Clinical trial information: NCT03601455.
Diabetic ketoacidosis.
Authors: G. D. Middleton, A. Mahmood, T. Hargreaves
Journal: BMJ (1970)

MEDICALJOUNL mEq/1.).It would therefore seem sensible to attempt to minimize the side effects experienced by the patient by making a special effort to keep the serum lithium in the lower therapeutic ranges.To reduce the peak rise to a minimum the lithium salt should be given in small divided doses at six-hourly intervals.Alternatively the use of a slow release compound might overcome this latter difficulty.One of the practical problems of deter- mining dosage by serum levels is that flame photometer estimations are only performed at selected centres.In Salford, where the estimations are carried out at only one of the hospital laboratories, we have found by a "split sample technique" that whole blood samples kept at room temperature for 24-48 hours give a valid result.If the serum is separated and kept at 4' C., apart from the duration of transportation, a valid reading can be obtained over a longer period.-Iam, etc.,
Amiodarone
Authors: John A. Oates, Alastair J.J. Wood, Jay W. Mason
Journal: New England Journal of Medicine (1987)

IN December 1985, amiodarone (Cordarone) was approved in the United States for treatment of life-threatening ventricular tachyarrhythmias. It is effective not only in these arrhythmias but also in less severe ventricular arrhythmias and many supraventricular arrhythmias, including atrial fibrillation and reentrant tachyarrhythmias involving accessory pathways. Its approval restricts its use to serious ventricular tachyarrhythmias, because amiodarone produces numerous side effects, some of which are serious.PharmacokineticsAmiodarone is absorbed slowly (the peak level is reached four to five hours after an oral dose), with low bioavailability that varies markedly among individuals.1 , 2 This low availability, and perhaps the variability, are thought . . .
Familial hyperglycerolemia.
Authors: C I Rose, D S Haines
Journal: Journal of Clinical Investigation (1978)

A 70-yr-old mildly diabetic white male was discovered to have an elevated level of serum free glycerol in the range of 75 mg/dl and to excrete about 13 g of free glycerol in the urine per 24 h. During a 24-h fast the urine glycerol loss increased to 21.5 g per 24 h. Studies carried out in vitro using leukocytes prepared from the patient's blood which were incubated with [14C]glycerol demonstrated an almost complete absence of glycerol oxidation to 14CO2 and of glycerol phosphorylation, in contrast to control studies with leukocytes collected from normal subjects. Homogenates of the patient's leukocytes contained negligible activity of ATP:glycerol phosphotransferase (glycerokinase EC 2.7.1.30) as measured by a direct spectrophotometric method. Marked hyperglycerolemia has thus far been detected in one brother and in one son of the daughter of this patient. This evidence suggests an x-linked recessive inheritance pattern of the trait. There is a high prevalence of diabetes mellitus in this family.
Depression in Cancer Patients
Authors: John R. Peteet
Journal: JAMA (1979)

Despite recent attention to death and dying, many questions remain about the diagnosis and treatment of depression in cancer patients. To provide a framework for effective treatment, this article distinguishes the following types of depression: (1) transient stress reactions, (2) major psychiatric disturbances requiring prompt attention, and (3) other depressive reactions. Depressions in the third general category, comprising the majority, are often mismanaged because of characterological, interpersonal, and organic factors receive insufficient attention. Understanding of such factors provides a basis for rational intervention with both patients and their families. (<i>JAMA</i>241:1487-1489, 1979)