tbuckley/cabot-search huggingface dataset:
Impact of lymph node yield at prostatectomy on outcomes in NRG/RTOG 9601.
Authors: Emily Chan, Stephanie L. Pugh, Jeff Simko, Felix Y Feng, William U. Shipley, Himanshu Lukka, Jean-Paul Bahary, Thomas Michael Pisansky, Kenneth Lee Zeitzer, Colleen Anne Lawton, Jason A. Efstathiou, Seth A. Rosenthal, Alexander G. Balogh, Richard Dana Lovett, Anthony C. Wong, Robert Timothy Dess, Scott McGinnis, Michael R. Kuettel, Lyudmila Demora, Howard M. Sandler
Journal: Journal of Clinical Oncology (2022)

265 Background: A recent study ( Fossati et al, 2018) found that higher lymph node count at radical prostatectomy was associated with improved outcomes in patients treated with salvage radiation for elevated prostate-specific antigen (PSA) after surgery. We sought to validate these results in NRG/RTOG 9601, a randomized controlled trial of men with pT2/T3 disease who underwent either radiation (RT) alone or RT+antiandrogen (bicalutamide) therapy for PSA elevation following radical prostatectomy from 1998-2003. Methods: We reviewed available pathology reports for all patients in NRG/RTOG 9601 to determine the nodal count at radical prostatectomy. Clinical data was as of 11/5/2015, same as the primary endpoint for the trial. Cox proportional hazards models were used to assess the effect of number of positive lymph nodes, treatment arm (RT alone or RT+bicalutamide), Gleason score, positive margins, and seminal vesicle invasion on the following endpoints: times to local and distant failure and overall and disease specific survival. Results: Out of the 760 patients originally eligible in the trial, 552 (73%, 276 in each arm) had complete data available. Median node count in the entire cohort was 6 (range 0-33, Q1-Q3 3-9). There were no significant differences between treatment arms in terms of patient demographic or clinical characteristics, including total lymph nodes removed in either arm (RT alone vs RT+bicalutamide median 5 vs 6, p = 0.11). There was no significant association between total lymph nodes and overall survival with both arms combined (HR = 1.00, 95% CI:0.97-1.03, p = 0.87) or in the individual arms alone (RT+Casodex: HR = 1.01, 95% CI:0.97-1.05, p = 0.65; RT+Placebo: HR = 0.98, 95% CI: 0.94-1.03, p = 0.45). There was also no significant association between total lymph nodes and disease-specific survival with both arms combined (HR = 1.00, 95% CI:0.95-1.04, p = 0.84) and in the arms alone (RT+Casodex: HR = 1.00, 95% CI:0.95-1.05, p = 0.92; RT+Placebo: HR = 0.99, 95% CI: 0.92-1.07, p = 0.86). In multivariable analysis performed on the two arms, Gleason score was the only feature associated with worse overall and disease-specific survival, seen only in the RT alone arm. Similar findings were seen when evaluating times to local and distant failure. Conclusions: Lymph node yield in NRG/RTOG 9601 did not show any association with adverse outcomes in the entire cohort, or in either treatment arm alone. The therapeutic benefit of an extensive lymph node dissection in this population remains uncertain. Clinical trial information: NCT00002874.
Parameters
Authors: R. G. Miller
Journal: BMJ (1966)

p. 1482) questions the factual basis for my tentative conclusion (21 May, p. 1301) that general practice may be the most appropriate setting for conducting clinical trials.Two types of defaulting in respect of adherence to treatment schedules must be distinguished, and perhaps should have been distinguished in my original letter.The first group are the " overt defaulters," and the second the " occult defaulters."The former fail to complete the trial for reasons which are obvious to the doctor-for example, volunteering that they have stopped the tab- lets, leaving the district, failing to reattend, etc. Being readily identifiable, their presence can be allowed for in the final assessment.It is the " occult defaulters " who may, and probably usually do, invalidate a trial.This group, having persevered, may appear to the unwary to have been entirely consonant to the treatment schedule, but in fact they have been dissonant.If my figures are examined, bearing in mind this distinction, then it can be seen that out of 29 " completers " 22 (76%) were available for assessment, and that only three of these patients were suspected as being definite defaulters.Can these figures be matched by any hospital outpatient trial ?I am, etc., Camberley,
Abstract 17162: Ambient Ultra Fine Particle Exposure Impairs Gut Vascular Barrier via Notch Signaling
Authors: Chih-Chiang Chang, Kyung In Baek, Yichen Ding, Constantinos Sioutas, Rongsong Li, Tzung Hsiai
Journal: Circulation (2018)

Introduction: Ultrafine particles (UFP, d &lt; 0.1 μm), a major sub-fraction of particulate matter (PM 2.5 , d &lt; 2.5μm) in air pollutant, have been reported to increase cardiovascular morbidity. UFP promote endothelial dysfunction/permeability associated with Notch inhibition and degradation of tight junction protein. Gut vascular barrier (GVB) is a distinct protective barrier that inhibits translocations of antigens across the gut lumen, preventing infections by oral digestions. Here, we hypothesized UFP impair GVB by attenuating Notch signaling and disrupting tight junction protein. Method: The transgenic Tg( flk1:mCherry ) zebrafish embryos were immobilized in neutralized tricaine solution and mounted in 2% low melting agarose to perform micro-gavage at 5 days post fertilizations (5dpf). A mA mixture of 10 kD FITC conjugated dextran and phenol red dye wasere micro-gavaged on the intestinal bulb with or without UFP at 25 μg/mL. Anterior trunk and posterior cardinal vein (PCV) post micro-gavage were imaged under a confocal microscope. Notch signaling related genes including the Notch ligand, Dll4, and the target, HES1, and the level of tight junction protein genes zonula occludens-1 (ZO-1) and Occludin (OCLN) mRNA expression following different courses of exposure to UFP were assessed in Human Aortic Endothelial Cells (HAEC) with quantitative RT-PCR., Result: In the control group, the majority of FITC-dextran remained inside the gastrointestinal system. On the other hand, UFP exposure developed a significant accumulation of FITC-dextran in the intersomatic spaces (ISS) between the dorsal aorta (DA) and the PCV. This finding supports evidence of UFP exposure disrupted both the epithelial boundary and the endothelial vascular layer of the gut. In addition, Notch signaling related gene (HES1, DLL4) and the tight junction proteins genes (ZO-1, OCLN) expressions in HAEC were downregulated in concentration and time-course dependent manner by the exposure to UFP. Conclusion: The UFP exposure affected GVB homeostasis and increased endothelial permeability. This finding supports the link between ambient air pollutant exposure to the impairment in the gastrointestinal system.
Mental health in people with covid-19
Authors: Ziyad Al-Aly
Journal: BMJ (2022)

In April 2021, we published a large-scale systematic characterisation of the clinical manifestations of long covid-the post-acute sequelae that result from an infection with SARS-CoV-2. 1 We followed people for six months and showed that covid-19 can lead to post-acute sequelae in nearly every organ system, including increased risk of mental health disorders.
Dexamethasone and Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia
Authors: Huanhuan Zheng, Shuangshan Bu
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) 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
Childhood autism.
Authors: J Rendle-Short
Journal: BMJ (1970)

it be generally appreciated that some children may bear several.Little difficulty should arise in babies of the Mongolian races (of whom up to 98 % may have one or more blue spots) unless the baby is very heavily pigmented.It is the occurrence of the melanocytes in the dermis of the darker- skinned African baby that gives rise to the appearance of a bruise, and it is therefore in African children that the mistake is most likely to occur.I need hardly add it becomes very embarrassing for the practitioner if he wrongly suspects a blameless mother of ill- treating her child through mistaking this not unusual and quite harmless lesion for bruising.Nearly all Mongolian blue spots will fade within a few months of birth; exceptionally they may last for a year or longer.-Iam, etc.,
Use of perioperative treatment (tx) among patients (pts) undergoing radical resection (RR) for muscle-invasive urothelial cancer (MIUC) in France, Germany, Italy, Spain, the United Kingdom, the United States, Canada, China, and Japan.
Authors: Edward I Broughton, Jürgen E. Gschwend, J. Alfred Witjes, Mia Berry, Michael Kostikas, Rachel Montgomery, Annabel Lambert, Siguroli Teitsson, Neil Milloy
Journal: Journal of Clinical Oncology (2022)

467 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by RR is the standard of care in cisplatin-eligible pts with MIUC. Adjuvant chemotherapy (AC) with cisplatin-based tx may be offered to those not given NAC. The unmet need this survey tried to evaluate is the post-RR burden of disease, quality of life (QoL) and perioperative tx patterns among MIUC pts. Methods: Real-world descriptive data were drawn from Adelphi’s MIUC Disease-Specific Programme: A point-in-time survey conducted with clinical/medical oncologists/urologists and their pts in 9 countries between January and June 2021. Physicians completed a survey on their pts’ clinical characteristics and tx patterns, while pts voluntarily completed a series of patient-reported outcome measures. Results: Of 2178 pts (data provided by 320 physicians), 30% received NAC only, 26% received AC only, 38% received no NAC or AC tx, and 6% received both. 1744 pts had initial tumour in the bladder; 35% received NAC only, 24% AC only, 35% no NAC or AC tx, and 6% received both. Of 387 pts with upper-tract urothelial carcinoma (UTUC), 51% received no NAC/AC tx, 35% received AC only, and 12% NAC only. More pts with T3 disease received no NAC/AC tx (36%) or NAC (35%) than AC (24%). Of 734 pts with nodal disease, 36% received NAC only. Of all pts, 60% experienced symptoms at data abstraction: 50% in pts who received NAC only, 71% in pts who received AC only and 82% in pts of those who received both. Pts reported similar EQ-5D-5L utility index scores (mean = 0.86; range: 0.84 [AC only] to 0.89 [NAC only]). Overall, feeling pain (40%) and stress (39%) were the EQ-5D domains with the worst scores. Pts who received AC only reported nominally lower EQ-5D visual analogue scale scores (71.11) compared with pts who received no NAC/AC (73.17) or pts who received NAC only (75.05). EORTC QLQ-C30 Global Health Status scores were 60.0 in pts who received AC only, 64.1 in pts who received NAC only or no NAC/AC, and 66.7 for pts who received both NAC and AC. Conclusions: Nearly 40% of pts remain untreated in either NAC or AC setting in 9 countries. A higher proportion of pts with UTUC go untreated. AC was more frequently used in UTUC vs BC pts; and in pts with Tis. NAC was implemented more frequently in pts T3 disease and in those with N+ disease. Pts who received AC appear to have nominally worse QOL and more symptoms, further demonstrating the need for efficacious adjuvant tx that does not decrease post-RR QoL.[Table: see text]
Neurosyphilis.
Authors: K. W. Heathfield
Journal: BMJ (1968)

haemoglobin fraction in the haemolysate may be due to its early intracellular precipitation.2This applies to the surplus of a-chains in f-thalassaernias, including the P-thalassaemia/ Hb E association'; it holds in part for the surplus of P-chains in a-thalassaemia inter- media."I suggest that in Hb E/a-thalassaemia the expected excess of ,E chains precipitates intracellularly.. Indeed, Dr. Wasi and his colleagues observed a small percentage of red cells with inclusion bodies, which they attri- buted to Hbp3,.It is not stated whether the inclusions were preformed in vivo or had developed in vitro.It is more probable that the precipitates are composed mainly, though not of necessity exclusively, of ,BE chains and that higher proportions of inclusions occur in red cell precursors.A low inclusion cell count in the circulation does not necessarily imply a minor degree of haemoglobin pre- cipitation.On the contrary, it may be due to early and extensive precipitation, leading to rapid selective removal of inclusions and/or affected cells and to enrichment in cells con- taining Hbye, which is the most stable tetramer of this class.If PE chains are less stable than 8A increasingly more fiA chains will be available to conibine with the short supply of a-chains and the A/E ratio will rise.Perhaps one should expect a series of tetrameric molecules If, f3l, PA, (3, (3A Id, 13, and P., in order of increasing stability; lability of these molecules will lead to some loss of MAchains as well, so that finally only minute quanties of free fA will be left over.The suggested preferential uptake of a-chains by PA relative to PE also may con- tribute to an increase of the A/E ratio.'However, in the relevant hybridization experiment MA chains outnumbered the PE chains from the start by a factor of four.Were competition solely responsible for the high A/E ratio, one would expect a large surplus of (E chains.Finally, greater instability of PE compared to PA is compatible with the fact that a-chain deficiency combined with Hb E is more severe, clinically and haematologically, than classical HFb H disease, although the imbalance of chain synthesis is more obvious in the latter.-Iam, etc.,
RECTAL PROLAPSE
Authors: J. P. Lockhart-Mummery
Journal: BMJ (1939)

By a prolapse of the rectum we mean an eversion of the bowel through the anal orifice as opposed to the pro- trusion of a polypus or other form of pedunculated tumour.A prolapse may take a number of different forms, and it is most important, if the condition is to be treated successfully, to be able to distinguish one from the other.
Pregnancy and Reproductive Risk Factors for Cardiovascular Disease in Women
Authors: Anna C. O’Kelly, Erin D. Michos, Chrisandra L. Shufelt, Jane V. Vermunt, Margo B. Minissian, Odayme Quesada, Graeme N. Smith, Janet W. Rich-Edwards, Vesna D. Garovic, Samar R. El Khoudary, Michael C. Honigberg
Journal: Circulation Research (2022)

Beyond conventional risk factors for cardiovascular disease, women face an additional burden of sex-specific risk factors. Key stages of a woman's reproductive history may influence or reveal short- and long-term cardiometabolic and cardiovascular trajectories. Early and late menarche, polycystic ovary syndrome, infertility, adverse pregnancy outcomes (eg, hypertensive disorders of pregnancy, gestational diabetes, preterm delivery, and intrauterine growth restriction), and absence of breastfeeding are all associated with increased future cardiovascular disease risk. The menopause transition additionally represents a period of accelerated cardiovascular disease risk, with timing (eg, premature menopause), mechanism, and symptoms of menopause, as well as treatment of menopause symptoms, each contributing to this risk. Differences in conventional cardiovascular disease risk factors appear to explain some, but not all, of the observed associations between reproductive history and later-life cardiovascular disease; further research is needed to elucidate hormonal effects and unique sex-specific disease mechanisms. A history of reproductive risk factors represents an opportunity for comprehensive risk factor screening, refinement of cardiovascular disease risk assessment, and implementation of primordial and primary prevention to optimize long-term cardiometabolic health in women.
Germline <i>BRCA2</i>, <i>ATM</i> and <i>CHEK2</i> alterations shape somatic mutation landscapes in prostate cancer.
Authors: Mari Nakazawa, Mike Fang, Tamara L. Lotan, Jun Luo, William B. Isaacs, Channing Judith Paller, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2022)

148 Background: Prostate cancer (PCa) is a highly heritable malignancy. Germline mutations in homologous recombination repair (HRR) genes, especially in in ATM, BRCA2 and CHEK2, are common in men with PCa, but how these influence somatic mutations is unknown. Characterizing the somatic landscape of tumors from germline HRR-altered PCa patients may provide insights into further therapeutic strategies and identify individuals most likely to benefit from existing therapies. Methods: We retrospectively identified 118 men with germline HRR-altered PCa from Johns Hopkins with available somatic mutation data (g ATM, n = 30; g BRCA2, n = 58; g CHEK2, n = 30). In these patients, somatic NGS analysis were done primarily using prostatic (rather than metastatic) tissues. The proportion of patients in each group with somatic biallelic inactivation was determined. We then compared the somatic mutation landscapes of the 3 groups, focusing on key PCa-relevant genes including AR, TMPRSS2-ERG, PTEN, TP53, BRCA2, ATM, CDK12, APC, FOXA1, AKT1, PIK3CA, and KDM6A among others. Somatic mutation data from primary prostate cancer specimens (n = 3965) found in pooled studies (n = 23) from cBioPortal were included as a reference standard for comparison. Results: Biallelic somatic inactivation was detected in 59% (34/58) of g BRCA2-altered, 47% (14/30) of g ATM-altered, and 0% (0/30) of g CHEK2-altered patients. In all 118 germline HRR-altered individuals, the most common somatic mutations were in BRCA2 (31%), FOXA1 (26%), TMPRSS2-ERG (20%), TP53 (16%), PTEN (15%), and ATM (15%). g BRCA2-altered patients had a higher prevalence of somatic mutations in AR (9% vs 3% in cBioPortal, P &lt; 0.05) and FOXA1 (29% vs 13% in cBioPortal, P &gt; 0.05), suggesting a greater dependency on AR signaling, but a lower prevalence of TMPRSS2-ERG fusions (17% vs 33% in cBioPortal, P &lt; 0.05). g ATM-altered patients had a strikingly low prevalence of somatic TP53 mutations (3% vs 25% in cBioPortal, P &lt; 0.01), indicating mutual exclusivity between these genes. g CHEK2-altered patients had a higher prevalence of somatic CDK12 mutations (10% vs 0% in gATM/gBRCA2 patients, P &lt; 0.05), implying an interaction between CHEK2 and CDK12. No differences were seen between the three groups with respect to alterations in the PI3K/PTEN pathway, WNT pathway, or chromatin-related genes. Conclusions: Biallelic inactivation was frequently observed in PCa patients harboring g ATM and g BRCA2 mutations, but not in those with g CHEK2 mutations. g BRCA2-altered patients were enriched for somatic AR (and FOXA1) mutations and were depleted for TMPRSS2-ERG fusions. g ATM-altered patients were depleted for somatic TP53 mutations, while g CHEK2-altered patients were enriched for somatic CDK12 mutations. Thus, germline mutations appear to impose selective pressures that influence somatic mutation landscapes in PCa.
Brigatinib Outperforms Crizotinib as First-Line Therapy
Journal: Cancer Discovery (2019)

The latest results from the phase III ALTA-1L trial suggest that the ALK inhibitor brigatinib is superior to crizotinib in patients with untreated non-small cell lung cancer. Brigatinib yielded a longer progression-free survival, a higher objective response rate, and greater effectiveness against brain metastases-and was less detrimental to patients' quality of life.
First-line therapy for metastatic renal cell carcinoma with pancreatic metastases: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).
Authors: Eduard Roussel, Lisa Kinget, Benoit Beuselinck, Maarten Albersen, Connor Wells, Matthew Scott Ernst, Frede Donskov, Andrew Lachlan Schmidt, Bernadett Szabados, Sumanta K. Pal, Luis A Meza, Neeraj Agarwal, Andrew James Weickhardt, Ian D. Davis, Ajjai Shivaram Alva, Lori Wood, Camillo Porta, Toni K. Choueiri, Daniel Yick Chin Heng, Vishal Navani
Journal: Journal of Clinical Oncology (2022)

317 Background: Metastatic renal cell carcinoma (mRCC) with pancreatic metastases (PM) is characterised by heightened angiogenesis, which is associated with improved outcomes with vascular endothelial growth factor (VEGF) inhibitors. We aimed to compare the efficacy of first-line (1L) ipilimumab/nivolumab (IOIO) vs. anti-PD(L)1/anti-VEGF (IOVE) vs. VEGF monotherapy (VE) in mRCC patients with and without PM. Methods: We performed a retrospective analysis of patients with and without PM, using the IMDC. Sites of metastases were captured at initiation of 1L. Patients with PM could also have metastases at other sites. We studied overall survival (OS) from start of 1L therapy using Cox regression, adjusted for IMDC risk groups. Kaplan Meier survival curves were generated. Results: 543/7,634 (7%) patients had PM. Patients with PM in the overall population had improved OS compared to those without, 56 vs 25.6 months respectively (HR 0.63, 95% CI 0.55-0.73, p&lt;0.0001). When examining the effect of PM within 1L options, those treated with IOVE exhibited a longer OS if PM were present vs absent, median not reached vs 45 months respectively (HR 0.41, 95% CI 0.18-0.93 p=0.03). This association was also seen in patients with treated with 1L VE, in those with PM vs absent, median 53.1 vs 25.1 months respectively (HR 0.65, 95% CI 0.55-0.76, p &lt;0.0001). Contrastingly there was no difference in median OS of patients with or without PM in patients receiving IOIO, 41.4 vs 44.4 months respectively (HR 0.86, 95% CI 0.48-1.56, p=0.62). Comparing the outcomes between 1L therapies in patients with PM the median OS of IOVE vs VE was not reached vs 53.1 months respectively (HR 0.37, 95% CI 0.16-0.83 p=0.02). Conversely, upfront VE and IOIO had a similar median OS of 53.1 vs 41.4 months respectively (HR 0.81, 95% CI 0.45-1.47 p=0.49). We were unable to find any difference in OS between those treated with IOVE vs IOIO, median not reached vs 41.4 months respectively (HR 0.52 95%, CI 0.19-1.45, p=0.21), but the low event rate limited this interpretation. Conclusions: We found that the presence of PM leads to an indolent biological behavior and was associated with improved outcomes when 1L therapy included a VE component. PM patients had comparable OS outcomes on 1L VE and 1L IOIO therapy, but improved OS when treated with 1L IOVE. Anti-angiogenic therapy may be necessary to optimize outcomes in PM and this warrants prospective evaluation. [Table: see text]
Spontaneous haemopneumothorax
Authors: F. E. Abyholm, G. Storen
Journal: Thorax (1973)

Spontaneous haemopneumothorax is a rare disease and is reported in 2% to 5% of hospital series of spontaneous pneumothorax. In Ullevål Hospital, Surgical Department III, 228 cases of spontaneous pneumothorax were treated in the period 1960-70. Of these, five patients had haemopneumothorax, that is, approximately 2·2%. The treatment is surgical with effective drainage and replacement of blood loss. If full expansion of the lung and cessation of haemorrhage is not effected in the course of the first few days, thoracotomy should be resorted to with the intention of arresting the bleeding and sealing leakage from the lung surface by resection of areas with emphysematous bullae.