tbuckley/cabot-search huggingface dataset:
Symptomless Myelomatosis
Authors: G. P. Baker, N. H. Martin
Journal: BMJ (1959)

say which.The inflammatory reaction in the tissues is of a very low oider such as may accompany any reconstruction of bone."Culture from the right hip and guinea-pig inoculation showed no evidence of tuberculosis. DiscussionThis patient has been the subject of wide interest, and a number of opinions have been obtained in respect of the aetiology of her arthritis.All observers agree that osteoarthritis was the primary joint disease.The slow progression from onset in 1937 to the inception of treatment in 1956 contrasted with the florid advance of joint destruction culminating in complete disorganization during 'the period of therapy with intra-articular injections of hydrocortisone acetate.The final picture, both clinical and radiographic, was indistinguishable from the condition described by Charcot.There was no evidence of neurological disease.Rheumatoid arthritis, tuberculosis, and other infective processes were excluded by serological tests and the results of biopsy.The striking similarity of this picture to that of neuropathic arthritis suggests that temporary suppression of pain of local origin by frequent intra- articular injection encourages a damaging degree of movement and weight-bearing.This in turn permits the development and rapid progression of joint destruction.The deterioration observed in this patient during treatment with locally injected hydrocortisone suggests that the procedure is potentially dangerous.This is particularly so since it has been our experience that symptomatic benefit from injections may lead to a vicious circle of dependence despite worsening disease.Careful radiological supervision is desirable if prolonged treatment by intra-articular injections of hydrocortisone and related compounds is undertaken. SummaryThe development of a severe destructive and relatively painless arthritis (Charcot joint) is reported during prolonged treatment of an osteoarthritic hip with intra- articular injections of hydrocortisone acetate.The need for careful radiological supervision during such treatment is emphasized.
Association between thermal responses, medical events, performance, heat acclimation and health status in male and female elite athletes during the 2019 Doha World Athletics Championships
Authors: Sebastien Racinais, George Havenith, Polly Aylwin, Mohammed Ihsan, Lee Taylor, Paolo Emilio Adami, Maria-Carmen Adamuz, Marine Alhammoud, Juan Manuel Alonso, Nicolas Bouscaren, Sebastian Buitrago, Marco Cardinale, Nicol van Dyk, Chris J Esh, Josu Gomez-Ezeiza, Frederic Garrandes, Louis Holtzhausen, Mariem Labidi, Gűnter Lange, Alexander Lloyd, Sebastien Moussay, Khouloud Mtibaa, Nathan Townsend, Mathew G Wilson, Stephane Bermon
Journal: British Journal of Sports Medicine (2022)

To determine associations between thermal responses, medical events, performance, heat acclimation and health status during a World Athletics Championships in hot-humid conditions.From 305 marathon and race-walk starters, 83 completed a preparticipation questionnaire on health and acclimation. Core (Tcore; ingestible pill) and skin (Tskin; thermal camera) temperatures were measured in-competition in 56 and 107 athletes, respectively. 70 in-race medical events were analysed retrospectively. Performance (% personal best) and did not finish (DNF) were extracted from official results.Peak Tcore during competition reached 39.6°C±0.6°C (maximum 41.1°C). Tskin decreased from 32.2°C±1.3°C to 31.0°C±1.4°C during the races (p<0.001). Tcore was not related to DNF (25% of starters) or medical events (p≥0.150), whereas Tskin, Tskin rate of decrease and Tcore-to-Tskin gradient were (p≤0.029). A third of the athletes reported symptoms in the 10 days preceding the event, mainly insomnia, diarrhoea and stomach pain, with diarrhoea (9% of athletes) increasing the risk of in-race medical events (71% vs 17%, p<0.001). Athletes (63%) who performed 5-30 days heat acclimation before the competition: ranked better (18±13 vs 28±13, p=0.009), displayed a lower peak Tcore (39.4°C±0.4°C vs 39.8°C±0.7°C, p=0.044) and larger in-race decrease in Tskin (-1.4°C±1.0°C vs -0.9°C±1.2°C, p=0.060), than non-acclimated athletes. Although not significant, they also showed lower DNF (19% vs 30%, p=0.273) and medical events (19% vs 32%, p=0.179).Tskin, Tskin rate of decrease and Tcore-to-Tskin gradient were important indicators of heat tolerance. While heat-acclimated athletes ranked better, recent diarrhoea represented a significant risk factor for DNF and in-race medical events.
Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia
Authors: S Degryse, C E de Bock, S Demeyer, I Govaerts, S Bornschein, D Verbeke, K Jacobs, S Binos, D A Skerrett-Byrne, H C Murray, N M Verrills, P Van Vlierberghe, J Cools, M D Dun
Journal: Leukemia (2017)

Mutations in the interleukin-7 receptor (IL7R) or the Janus kinase 3 (JAK3) kinase occur frequently in T-cell acute lymphoblastic leukemia (T-ALL) and both are able to drive cellular transformation and the development of T-ALL in mouse models. However, the signal transduction pathways downstream of JAK3 mutations remain poorly characterized. Here we describe the phosphoproteome downstream of the JAK3(L857Q)/(M511I) activating mutations in transformed Ba/F3 lymphocyte cells. Signaling pathways regulated by JAK3 mutants were assessed following acute inhibition of JAK1/JAK3 using the JAK kinase inhibitors ruxolitinib or tofacitinib. Comprehensive network interrogation using the phosphoproteomic signatures identified significant changes in pathways regulating cell cycle, translation initiation, mitogen-activated protein kinase and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signaling, RNA metabolism, as well as epigenetic and apoptotic processes. Key regulatory proteins within pathways that showed altered phosphorylation following JAK inhibition were targeted using selumetinib and trametinib (MEK), buparlisib (PI3K) and ABT-199 (BCL2), and found to be synergistic in combination with JAK kinase inhibitors in primary T-ALL samples harboring JAK3 mutations. These data provide the first detailed molecular characterization of the downstream signaling pathways regulated by JAK3 mutations and provide further understanding into the oncogenic processes regulated by constitutive kinase activation aiding in the development of improved combinatorial treatment regimens.
Efficacy of COVID-19 vaccines in patients taking immunosuppressants
Authors: Chen Shen, Malcolm Risk, Elena Schiopu, Salim S Hayek, Tiankai Xie, Lynn Holevinski, Cem Akin, Gary Freed, Lili Zhao
Journal: Annals of the Rheumatic Diseases (2022)

Objectives We intended to assess the effectiveness of all three US Food and Drug Administration approved COVID-19 vaccines at preventing SARS-CoV-2 infection and COVID-19 hospitalisation in a large cohort of individuals on immunosuppressants for a diverse range of conditions. Methods We studied the effectiveness of BNT162b2 (Pfizer–BioNTech), mRNA-1273 (Moderna) and Ad26.COV2.S (Johnson &amp; Johnson–Janssen) vaccines among individuals who take immunosuppressants (including disease-modifying antirheumatic drugs and glucocorticoids) by comparing vaccinated (n=97688) and unvaccinated (n=42094) individuals in the Michigan Medicine healthcare system from 1 January to 7 December 2021, using Cox proportional hazards modelling with time-varying covariates. Results Among vaccinated and unvaccinated individuals, taking immunosuppressants increased the risk of SARS-CoV-2 infection (adjusted HR (aHR)=2.17, 95% CI 1.69 to 2.79 for fully vaccinated and aHR=1.40, 95% CI 1.07 to 1.83 for unvaccinated). Among individuals taking immunosuppressants, we found: (1) vaccination reduced the risk of SARS-CoV-2 infection (aHR=0.55, 95% CI 0.39 to 0.78); (2) the BNT162b2 and mRNA-1273 vaccines were highly effective at reducing the risk of SARS-CoV-2 infection (n=2046, aHR=0.59, 95% CI 0.38 to 0.91 for BNT162b2; n=2064, aHR=0.52, 95% CI 0.33 to 0.82 for mRNA-1273); (3) with a smaller sample size (n=173), Ad26.COV2.S vaccine protection did not reach statistical significance (aHR=0.34, 95% CI 0.09 to 1.30, p=0.17); and (4) receiving a booster dose reduced the risk of SARS-CoV-2 infection (aHR=0.42, 95% CI 0.24 to 0.76). Conclusions The mRNA-1273 and BNT162b2 vaccines are effective in individuals who take immunosuppressants. However, individuals who are vaccinated but on immunosuppressants are still at higher risk of SARS-CoV-2 infection and COVID-19 hospitalisation than the broader vaccinated population. Booster doses are effective and crucially important for individuals on immunosuppressants.
Robot-assisted kidney transplantation as a minimally invasive approach for kidney transplant recipients: A systematic review and meta-analyses
Authors: Julia S. Slagter, Loubna Outmani, Khe T.C.K. Tran, Jan N.M. Ijzermans, Robert C. Minnee
Journal: International Journal of Surgery (2022)

Robot-assisted kidney transplantation (RAKT) has emerged as an alternative for kidney transplant recipients with the potential benefits of minimally invasive surgery. The aim of this systematic review and meta-analysis is to compare the clinical outcomes of RAKT with open kidney transplantation (OKT).MEDLINE, Embase, Web of Science and Cochrane databases were systematically searched. Baseline characteristics, intraoperative and postoperative outcomes were collected, as well as long-term renal function and data on graft and patient survival.Eleven studies were included, which compared 482 RAKT procedures with 1316 OKT procedures. RAKT was associated with lower a risk of surgical site infection (Risk ratio (RR) = 0.15, p < 0.001), symptomatic lymphocele (RR = 0.20, p = 0.03), less postoperative pain (Mean difference (MD) = -1.38 points, p < 0.001), smaller incision length (MD = -8.51 cm, p < 0.001), and shorter length of hospital stay (MD = -1.69 days, p = 0.03) compared with OKT. No difference was found in renal function, graft, and patient survival.RAKT is a safe and feasible alternative to OKT with less surgical complications without compromising renal function, graft and patient survival.
ATHLETIC PROGRAMS IN INDUSTRY
Journal: JAMA (1952)

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
Hypersomnia Syndromes
Authors: M. N. Pai
Journal: BMJ (1950)

IODINE AND GASTRIC FUNCTIONulcer and acute gastritis, the amount of free and total acid was 20-40 degrees higher than before.In patients with alcoholic gastritis the iodine test had no effect.The results obtained after the injection of iodine were similar to those obtained after the histamine test.Therefore it would be better to replace histamine by iodine in testing for gastric function.
Cervical Cytology
Authors: S. Way
Journal: BMJ (1969)

MEDIALJOUNL 763 cervical carcinoma.These, if spread over the suggested period of 20 years for the development of the disease, would present at the rate of 21 cases every year-thatt is, pre- cisely at the known annual incidence.It is therefore necessary for all the detected pre- clinical cases to progress to clinical cancer, if left untreated, to produce the expected number of clinical cases each year.The incidence of the disease has dropped in screened populations, both here2 and in British Columbia.The fall in mortality will follow because the precancerous lesions, which we believe would progress, have been removed after detection by screening tech- niques.In a disease with a 10-20 year latent period between the preclinical stage and death time must elapse until the results of screening can be reflected in mortality rates.As we have sa-id,2 and as has Way,4 efforts must be concentrated on encouraging the screening of women of all ages.In Aberdeen young women are screened antenatally, their names put on a computerized register, and they are automatically recalled for screening at five-yearly intervals.T~he older women are screened in co-operation with their own general practitioners, and may be recalled at shorter intervals.-Iam, etc.,
Diphtheria
Authors: R. S. Cross
Journal: BMJ (1859)

exciting c ause of irregular recuirrenice, all trace. of periodicity is lost.Tlhe patienit (loes not kIow wlihen to expect hiis attack.le imaiiy have o01) in a twelvemoiti.lie mnay ha.Uvo onDe to-mor- row, he may hlave four in a moultlh, h-e miiay go Years without one; it may never occur at two intervals alike, an:d when it dloes occur he is perfectly at a loss to saty wvhy it shoul(d choose that particuilar period.T'lhe timiie of its re,currence and its frequiency are alike inexplicable.He may be living in perfect hlaldh andi daily diread.To express suininaiiliv, tfle, -what appear to lbe the facts wvith regard to thie period iity of asthmia, wve may sa-- L. That asthmia is typically periodic.2. That, though there is a period( for each calse, there is no particuilar period for thie disease in gnernal.3. That the Peri(licity of' asthnna is of two kin(ds, intrinsic and extrinsic, the latter a spr.urious pelioclicity, dependent orn the peliodic oeci-ee of the exciting cauSe; the fornier, the true essential periolicity.independent of a:l external circum-l- stances.
Trends in and Factors Associated With Out-of-Pocket Spending for COVID-19 Hospitalizations From March 2020 to March 2021
Authors: Kao-Ping Chua, Rena M. Conti, Nora V. Becker
Journal: JAMA Network Open (2022)

Advantage CommericalFacility services are those billed by hospitals, such as room-and-board charges.The ocurrence of cost sharing for these services may be an indicator that the hospitalization was covered by a plan that lacked a cost-sharing waiver for COVID-19 hospitalizations.
Temporary Spinal Cord Stimulation to Prevent Postcardiac Surgery Atrial Fibrillation
Authors: Alexander Romanov, Vladimir Lomivorotov, Alexander Chernyavskiy, Vladimir Murtazin, Elena Kliver, Dmitry Ponomarev, Igor Mikheenko, Alexander Yakovlev, Marina Yakovleva, Jonathan S. Steinberg
Journal: Journal of the American College of Cardiology (2022)
Targeting macrophagic SHP2 for ameliorating osteoarthritis via TLR signaling
Authors: Ziying Sun, Qianqian Liu, Zhongyang Lv, Jiawei Li, Xingquan Xu, Heng Sun, Maochun Wang, Kuoyang Sun, Tianshu Shi, Zizheng Liu, Guihua Tan, Wenqiang Yan, Rui Wu, Yannick Xiaofan Yang, Shiro Ikegawa, Qing Jiang, Yang Sun, Dongquan Shi
Journal: Acta Pharmaceutica Sinica B (2022)

Osteoarthritis (OA), in which M1 macrophage polarization in the synovium exacerbates disease progression, is a major cause of cartilage degeneration and functional disabilities. Therapeutic strategies of OA designed to interfere with the polarization of macrophages have rarely been reported. Here, we report that SHP099, as an allosteric inhibitor of src-homology 2-containing protein tyrosine phosphatase 2 (SHP2), attenuated osteoarthritis progression by inhibiting M1 macrophage polarization. We demonstrated that M1 macrophage polarization was accompanied by the overexpression of SHP2 in the synovial tissues of OA patients and OA model mice. Compared to wild-type (WT) mice, myeloid lineage conditional Shp2 knockout (cKO) mice showed decreased M1 macrophage polarization and attenuated severity of synovitis, an elevated expression of cartilage phenotype protein collagen II (COL2), and a decreased expression of cartilage degradation markers collagen X (COL10) and matrix metalloproteinase 3 (MMP3) in OA cartilage. Further mechanistic analysis showed thatSHP099 inhibited lipopolysaccharide (LPS)-induced Toll-like receptor (TLR) signaling mediated by nuclear factor kappa B (NF-κB) and PI3K-AKT signaling. Moreover, intra-articular injection of SHP099 also significantly attenuated OA progression, including joint synovitis and cartilage damage. These results indicated that allosteric inhibition of SHP2 might be a promising therapeutic strategy for the treatment of OA.
SUB-urothelial durvalumab injection: 1 (SUBDUE-1)—Results from the first nine urothelial cancer patients using a dose-escalation schedule.
Authors: Dickon Hayne, Nicole Swarbrick, Stephen McCombie, Andrew Moe, Cynthia Hawks, Pravin Viswambaram, Ciara Conduit, Elizabeth Chien Hern Liow, Lisa Spalding, Jarrad Bothe, Tom Ferguson, Andrew James Martin, Ian D. Davis, Andrew David Redfern
Journal: Journal of Clinical Oncology (2022)

483 Background: The sub-urothelial administration of checkpoint inhibitors has not been reported. This approach could be safer and more efficacious than systemic delivery for patients with non-muscle-invasive bladder cancer (NMIBC). Methods: This phase 1b study employed a 3+3 dose-escalation design to explore tolerability, safety and immunological efficacy of sub-urothelial durvalumab, a programmed death-ligand 1 (PDL1) monoclonal antibody. Eligible participants had high risk NMIBC or MIBC without prior chemotherapy or immunotherapy (BCG allowed) and were planned for cystectomy. Participants received 25/75/150mg durvalumab diluted in 25mL normal saline injected into the sub-urothelium at 25 locations (25x1mL injections), at least 2 weeks prior to radical cystectomy. Systematic four quadrant cold cup bladder biopsies were taken immediately prior to durvalumab injection and immediately prior to cystectomy. Tumour, if present, was biopsied before and after injection and bladder maps recorded. International Prostate Symptom Index (IPSS) and O’Leary symptom score at various time points and adverse events (AE) as per CTCAE (Version 4) were recorded. Relative changes in immune cell counts (RCI) on bladder biopsy for CD3, CD8, CD68 and CD168 expressing cells are reported (value &gt;1.0 designating increase). Results: Nine participants were recruited; eight male (89%), 1 female; mean age 72 years (range 56 – 82). No dose-limiting toxicities were observed. No evidence of treatment-related effect on IPSS or O’Leary Symptom scores was seen. Fourteen AEs were reported by six (67%) patients: 10 were Grade 1, 3 Grade 2, 1 Grade 3. None were considered immune- or treatment-related by investigators. Transient elevation of peri-operative thyroid stimulating hormone was seen in two subjects, which normalised without intervention. No hepatitis was seen. All patients underwent planned cystectomy. RCI of different immune populations was calculated (see Table). Visible tumour was present in only 4 patients limiting interpretation of RCI. RCI varied significantly between cell types (p=0.008*). RCI numerically increased by dose but did not reach statistical significance (p=0.076**). A numeric increase in monocytes was seen at 150mg dose. RCI of different immune populations by dose of sub-urothelial durvalumab. Conclusions: Sub-urothelial injection of durvalumab was safe at all 3 dose levels without any drug-related adverse events. Immunological studies showed differential effects on immune cells with macrophage population most affected. Further studies investigating the role of 150mg sub-urothelial durvalumab in the management of NMIBC are planned. Clinical trial information: ACTRN12620000063910.[Table: see text]
Elucidating the effect of geriatric parameters on COVID-19 outcomes for older adults with cancer
Authors: Martine Milton, Joanne Jethwa, Nicolò Matteo Luca Battisti
Journal: The Lancet Healthy Longevity (2022)

A diagnosis of active cancer is associated with a higher risk of severe COVID-19 than no diagnosis.1 Increasing age and comorbid conditions are also independently associated with severe COVID-19.2 Therefore, older adults with cancer are disproportionately disadvantaged during the pandemic (although many studies to support this statement were done before the availability of effective COVID-19 vaccines). In this context, COVID-19 might challenge the equal and evidence-based management of older adults with cancer.
Acute renal failure.
Authors: A M Martin, G Venkatraman, P Trinder, C Stones
Journal: BMJ (1980)

gists stated that "the appearances are those of idiopathic retroperitoneal fibrosis.The histological appearances of practolol peritonitis are different...." This is not the appropriate comparison.The patient obviously had fibrosis in the retroperitoneal space and not the peritoneal cavity.The point is that idopathic and drug-related (for example, methysergide) retroperitoneal fibrosis present the same histological picture.'Oxprenolol is also listed in reports of the Committee on Safety of Medicines as being ingested by patients developing sclerosing
PSMA PET in Prostate Cancer—A Biomarker or a Surrogate End Point?—Reply
Authors: Thomas A. Hope, Jeremie Calais
Journal: JAMA Oncology (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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2022 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 Oncology journal