tbuckley/cabot-search huggingface dataset:
Identifying longitudinal clusters of multimorbidity in an urban setting: A population-based cross-sectional study
Authors: Alessandra Bisquera, Martin Gulliford, Hiten Dodhia, Lesedi Ledwaba-Chapman, Stevo Durbaba, Marina Soley-Bori, Julia Fox-Rushby, Mark Ashworth, Yanzhong Wang
Journal: The Lancet Regional Health - Europe (2021)

Globally, there is increasing research on clusters of multimorbidity, but few studies have investigated multimorbidity in urban contexts characterised by a young, multi-ethnic, deprived populations. This study identified clusters of associative multimorbidity in an urban setting. This is a population-based retrospective cross-sectional study using electronic health records of all adults aged 18 years and over, registered between April 2005 to May 2020 in general practices in one inner London borough. Multiple correspondence analysis and cluster analysis was used to identify groups of multimorbidity from 32 long-term conditions (LTCs). The population included 41 general practices with 826,936 patients registered between 2005 and 2020, with mean age 40 (SD15·6) years. The prevalence of multimorbidity was 21% (n = 174,881), with the median number of conditions being three and increasing with age. Analysis identified five consistent LTC clusters: 1) anxiety and depression (Ratio of within- to between- sum of squares (WSS/BSS <0·01 to <0·01); 2) heart failure, atrial fibrillation, chronic kidney disease (CKD), chronic heart disease (CHD), stroke/transient ischaemic attack (TIA), peripheral arterial disease (PAD), dementia and osteoporosis (WSS/BSS 0·09 to 0·12); 3) osteoarthritis, cancer, chronic pain, hypertension and diabetes (0·05 to 0·06); 4) chronic liver disease and viral hepatitis (WSS/BSS 0·02 to 0·03); 5) substance dependency, alcohol dependency and HIV (WSS/BSS 0·37 to 0·55). Mental health problems, pain, and at-risk behaviours leading to cardiovascular diseases are the important clusters identified in this young, urban population. Impact on Urban Health, United Kingdom.
Anlotinib plus TQB2450 in patients with advanced refractory biliary tract cancer (BTC): An open-label, dose-escalating, and dose-expansion cohort of phase Ib trial.
Authors: Jun Zhou, Jifang Gong, Yanshuo Cao, Zhi Peng, Jiajia Yuan, Xicheng Wang, Ming LU, Lin Shen
Journal: Journal of Clinical Oncology (2021)

292 Background: Anti-angiogenic agents have been clinically investigated in combination with anti-PD-1/L1 mAbs due to their immuno-modulatory effects. Anlotinib (A), a potent oral multi-target tyrosine kinase inhibitor, has anti-angiogenic properties and anti-tumor efficacy with a favorable toxicity profile. The combination of A and TQB2450 (T), an anti-PD-L1 mAb, exhibited superior tumor growth suppression compared to either monotherapy in murine models. This ongoing phase 1b study cohort is aimed to assess the safety and efficacy of A+T in pts with advanced BTC. Methods: In this study cohort, patients (pts) with previously treated, advanced BTC were enrolled. A 3+3 dose escalation was used to determine the maximum tolerated dose (MTD) and a recommended phase 2 dose (RP2D) in a dose-escalating stage. Additional pts were enrolled in a dose-expansion stage to further establish the safety and determine the preliminary efficacy. Oral A of 10 and 12 mg was administered once daily for 14 days on / 7 days off with intravenous T of 1200 mg every 3 weeks. The primary endpoint was dose-limiting toxicity (DLT) during first cycle (first 3 weeks) to estimate the MTD, RP2D and overall response rate (ORR). Tumor response was assessed according to RECIST version 1.1 and iRECIST. The Secondary endpoints were progression-free survival (PFS), disease control rate (DCR) and safety. Results:25 pts were enrolled (8 with intrahepatic cholangiocarcinoma [IHCC]; 8 with extrahepatic cholangiocarcinoma [EHCC]; 9 with gall bladder cancer [GBC]) until August 2020. Median number of prior lines of therapy was 1 (range 1-5). During dose-escalation, no DLT was observed and 12 mg anlotinib was determined as RP2D for expansion. Among 24 evaluable pts (with at least once tumor assessment), 3 had achieved complete response (CR) and 7 had partial response (PR), which were all treated by 12 mg anlotinib plus TQB2450, 8 had stable disease (SD) and 6 had progression disease (PD). ORR was 41.67% and DCR was 75%. 10 pts were still on treatment. The median PFS was 240 days (95% CI, 83~NR).Treatment-related adverse events (TRAEs) occurred in 83.3% of pts (G3/4 in 16.7% [4/24], and leading to treatment discontinuation in 4.2% [1/24]). The most common TRAEs were hypertension (33.3%), decreased white blood cell counts (25.0%), increased TBIL (20.8%), decreased neutrophil counts (20.8%), increased DBIL (12.5%), and increased IBIL (12.5%). Conclusions: A+T had a manageable safety profile and encouraging antitumor efficacy in pts with previously treated, advanced BTC. No unexpected AEs were identified beyond the established safety profile for each agent. Clinical trial information: NCT03996408.
Portasystemic Venous Shunts
Authors: Ronald A. Malt
Journal: New England Journal of Medicine (1976)

[Emergency end-to-side portacaval shunt.] For dependable relief of portal hypertension, emergency shunts for bleeding varices must decompress the splanchnic system immediately draining into the portal vein; in practice, the options for gaining this goal are overwhelmingly the portacaval and H-graft mesocaval shunts. Peripheral splanchnic shunts are considerably less effective.Although the quality of life after an emergency shunt compared with life after an elective shunt has not been scrutinized, it seems reasonable to recommend an urgent end-to-side portacaval shunt (within 18 hours of the bleeding episode) for Child's class A patients who would otherwise be offered . . .
Molecular profiling of advanced pancreatic ductal adenocarcinoma (PDAC): Role of ctDNA.
Authors: Angela Lamarca, Mairead Geraldine McNamara, Richard Hubner, Juan W. Valle
Journal: Journal of Clinical Oncology (2021)

425 Background: Molecular profiling of tumour samples and circulating tumour DNA (ctDNA) may inform treatment of advanced cancer; the role of ctDNA to predict progression-free-survival (PFS) and overall survival (OS) in advanced PDAC is not fully understood. Methods: Eligible patients: those diagnosed with advanced PDAC undergoing molecular profiling [tumour (Foundation Medicine CDx/Caris) or ctDNA (FoundationMedicine Liquid (72 cancer-related genes))]. Baseline patient characteristics and molecular profiling outcomes, including mutant allele frequency (MAF) for pathological alterations were extracted. The primary aim was to assess the impact of presence of ctDNA at time of systemic chemotherapy initiation on PFS and OS. Results: Total of 26 samples (ctDNA 18 samples and 8 tumour samples) from 25 patients diagnosed with advanced PDAC underwent molecular profiling. When the whole population was analysed, the rate of sample analysis failure seemed to be higher when tumour tissue was tested (37.5%) compared to ctDNA (5.56%); p-value 0.072. The overall rate of identification of pathological findings was 72.73%, with 18.18% of patients having targetable findings [EGFRmut (1 patient), KRAS G12C mut (1 patient), FGFR2 fusion (1 patient), RNF43 mut (1 patient)]; these findings impacted treatment management in one patient only (RNF43 mutation; Wnt inhibitor). Variants of unknown significance were identified in 63.64% of samples. Patients with ctDNA analysis at time of palliative chemotherapy initiation (16 samples; 15 patients) were analysed [6 female (40.00%), median age 69.57 years (range 51.61-81.49), metastatic disease (66.67%), 80% first-line (80%), 20% second-line]. Pathological mutations were identified in 9/15 (60.00%) of these patients (KRAS mutation identified in 6/9). After median follow-up of 8.33 months from sample acquisition, 80% and 53.33% of patients had progressed and died, respectively. Median estimated PFS and OS were 5.65 months (95% CI 1.59-8.17) and 7.80 months (95% CI 4.13-not reached). Presence (vs absence) of pathological alterations in ctDNA showed a trend towards shorter PFS (2.91 vs 6.51 months; HR 1.38 (95% CI 0.40-4.77)) and OS (6.12 vs 9.72 months; HR 2.03 (95% CI 0.60-6.82)). Conclusions: This pilot study demonstrates the feasibility of ctDNA analysis in patients with advanced PDAC prior to initiation of palliative therapy. The presence of pathological alterations in ctDNA may prognosticate for worse PFS and OS. Larger studies are required to confirm these findings.
SP0075 Macrophage activation syndrome and systemic jia
Authors: W Kuis, NM Wulffraat, GT Rijkers
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> Systemic JIA is characterised not only by arthritis, but also by systemic features such as intermittent fever, lymphadenopathy, hepato-splenomegaly, exanthema and serositis. The disease occurs predominantly in childhood. It often begins at a young age and usually has a serious outcome, although new therapeutic regimes like high dose methotrexate, cyclosporine-A and TNF-α blockade have improved the prognosis. A serious complication of systemic JIA is the Macrophage Activation Syndrome (MAS), which is often triggered by infections and medicines like gold and sulfasalazine. MAS is characterised by persistent high fever, mild to serious derangements of liver cell functions, purpura, encephalopathy and disseminated intravascular coagulation. Laboratory investigations often show a leucocytopenia, thrombocytopenia and anaemia in combination with elevated levels of bilirubin and hepatic enzymes. In the bone marrow and other organs like the lymphglands, liver and brain, haemophagocytizing histiocytes are demonstrable. Although they are not specific for MAS, the presence of haemophagocytizing histiocytes together with the other specific clinical symptoms enables the clinician to make the diagnosis. MAS is a very serious, life-threatening complication of systemic JIA, which has to be treated with high dose corticosteroids, often in combination with cyclosporine. Even with this regimen the mortality rate is high. Familial Haemophagocytic Lymphohistiocytosis (FHL), a congenital disease of childhood, is also characterised by haemophagocytosis. Recently, a defect in the perforin gene was found in patients with FHL. Because of the resemblance with MAS in systemic JIA, we have also investigated the perforin expression on cytotoxic CD8<sup>+</sup><sup>ve</sup> effector T-cells and NK-cells. We find a decreased expression of perforins in systemic JIA, which could play a role in the pathogenesis of the disease.
Engineering the Lymphatic Network: A Solution to Lymphedema
Authors: Wenkai Jia, Hannah Hitchcock‐Szilagyi, Weilue He, Jeremy Goldman, Feng Zhao
Journal: Advanced Healthcare Materials (2021)

Abstract Secondary lymphedema is a life‐long disorder characterized by chronic tissue swelling and inflammation that obstruct interstitial fluid circulation and immune cell trafficking. Regenerating lymphatic vasculatures using various strategies represents a promising treatment for lymphedema. Growth factor injection and gene delivery have been developed to stimulate lymphangiogenesis and augment interstitial fluid resorption. Using bioengineered materials as growth factor delivery vehicles allows for a more precisely targeted lymphangiogenic activation within the injured site. The implantation of prevascularized lymphatic tissue also promotes in situ lymphatic capillary network formation. The engineering of larger scale lymphatic tissues, including lymphatic collecting vessels and lymph nodes constructed by bioengineered scaffolds or decellularized animal tissues, offers alternatives to reconnecting damaged lymphatic vessels and restoring lymph circulation. These approaches provide lymphatic vascular grafting materials to reimpose lymphatic continuity across the site of injury, without creating secondary injuries at donor sites. The present work reviews molecular mechanisms mediating lymphatic system development, approaches to promoting lymphatic network regeneration, and strategies for engineering lymphatic tissues, including lymphatic capillaries, collecting vessels, and nodes. Challenges of advanced translational applications are also discussed.
FRI0197 Prostaglandin e1 infusions and plasma homocysteine in systemic sclerosis
Authors: M Massarotti, C Maioli, A Bestetti, R Coppola, S Leviti, B Marasini
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Although elevated plasma levels of homocysteine (Hcy) are considered a risk factor for vascular events, it is still uncertain if the lowering of Hcy by folate restores endothelial function. <h3>Objectives</h3> We evaluated the relationship between Hcy and endothelial damage in systemic sclerosis (SSc), measuring plasma levels of von Willebrand factor (vWf), a well accepted marker of endothelial dysfunction, and Hcy, after treatment with PGE1, which has no known interferences with Hcy metabolism and whose long-term benefit is thought to be due to improvement of endothelial function. <h3>Methods</h3> Sixty mcg PGE1 (alprostadil alpha-cyclodextrine) in 250 ml 0.9% saline daily were infused daily for a 5 days-period (1st cycle), and after 1 and 2 months for 1 day-period thereafter (2nd and 3rd cycle, respectively) to 10 SSc patients (2 with the diffuse, dSSc, 7 with the limited type, lSSc, 1 with SSc sine scleroderma. Hcy (immunoassay), vWf (ELISA) and folic acid (radioassay) were measured before each cycle. <h3>Results</h3> Hcy was reduced vs baseline before the 2nd and 3rd cycle (11.30 ± 3.23 and 12.16 ± 4.86 vs 14.46 ± 5.31 mcM/L, p &lt; 0.005 and p = 0.0616, respectively; mean ± SD), with a percent decrease vs baseline significantly greater in dSSc vs lSSc (66.0 ± 9.7 vs 83.1 ± 7.0%, p &lt; 0.03 and 64.2 ± 14.5 vs 88.4 ± 6.0%, p &lt; 0.05, 2nd and 3rd cycles). vWf was also reduced (167 ± 39 and 156 ± 27 vs 183 ± 12 U/dl, p &lt; 0.05), with no differences between lSSc or dSSc. Folic acid did not change (4.68 ± 1.56, 4.94 ± 2.09 and 4.54 ± 1.71 ng/ml). No relationship was observed between Hcy and vWf. <h3>Conclusion</h3> These data are consistent with Hcy as a marker rather than a risk for endothelial damage. Further studies are however needed to evaluate the relatioship of Hcy and vWf plasma levels with endothelial function.
Michael Green: forensic pathologist whose observations helped catch the “Yorkshire Ripper”
Authors: John Illman
Journal: BMJ (2021)

Credit: Jennifer Green

Within five weeks in 1975, Michael Green, then a senior lecturer in forensic in Leeds, examined two local women who had survived brutal attacks. Both had been hit on the head from behind with a hammer. Green warned the police that the same person had almost certainly carried out both attacks He was right. These were the first recorded assaults by Peter Sutcliffe, later dubbed the Yorkshire Ripper.

Within a few months Sutcliffe murdered two women, again attacking from behind with a hammer. Green was convinced a serial killer was at large, but because the second two women had been prostitutes, the police regarded their attacks as separate from the first two—a major error.

It wasn’t until 1978—after seven similar murders—that the police finally heeded Green’s advice. Sutcliffe subsequently confessed to 13 murders and seven attempted murders.

In 1982, shortly after Sutcliffe’s long overdue arrest, Green addressed Britain’s most senior police officers at a conference in Oxford. Green’s lecture, provocatively entitled “Is Sir Bernard Spilsbury dead?” highlighted the celebrated man purported to be Britain’s first ever forensic pathologist. Spilsbury, who helped to solve many gruesome cases, had a reputation for giving definitive evidence. Most famously, he provided the critical evidence that sent the notorious Dr Crippen to the gallows in 1910 for the murder of his wife.

The …
Inequality is hidden in plain sight
Authors: John Robson, Alexander Miller, Jayne Taylor, Kambiz Boomla, Sally Hull, Carol Dezateux
Journal: BMJ (2021)

We agree with Moscrop and colleagues that socioeconomic inequalities are being hidden in plain sight by area based "averaging" of social disadvantage, which blunts social gradients and conceals pockets of disadvantage like hostels or homeless people. 1 Area based scores such as the index of material deprivation (IMD) are important tools, but they lack resolution at an individual level, particularly where the urban or rural affluent rub shoulders with the most disadvantaged people in the same postcodes.In 2019 Hackney Council used a stratified random sample to interview 1024 Hackney residents aged 16 years and over.Participants were asked the question, "Do you ever have difficulty making ends meet at the end of the month?" with the answers always (5%), sometimes (33%), rarely/never (60%), or preferred not to say (2%). 2 3 Responses were compared with the average IMD in the participants' postcodes.Reported smoking status, Short Warwick-Edinburgh Mental Wellbeing Scale, and health impairment were also included.Self-reported economic circumstance was associated with greater discrimination of reported indices than area based IMD scores.The descriptive figures can be viewed at https://www.qmul.ac.uk/blizard/ceg/re-search/recordinginequalities/.Asking people to report their own economic circumstances is comparable to general practitioners collecting data on self-reported ethnic group, which we have successfully pioneered throughout east London in over 90% of adults.4 This was achieved with staff training, standard data entry templates, and initial financial incentives to promote this now routine data collection that was recently mandated nationally.A similar approach could be taken to record self-reported economic situation, which would transform knowledge about the socioeconomic circumstance of patients, relevant to planning, public health, and direct care.IMD is based on census information with partial updating every 4-5 years.General practice could do at least as well for individually self-reported socioeconomic status.Evaluation of pilots of implementation across a variety of locations would be a suitable next step.
COVID-19 pandemic: Patients'perspective during cancer treatment
Authors: F. Merloni, N. Ranallo, L. Bastianelli, F. Vitarelli, L. Cantini, Z. Ballatore, G. Ricci, I. Fiordoliva, L. Tassone, B. Ferretti, P. Alessandroni, M. Del Prete, S. Chiorrini, S. Mobin, R. Ficarelli, G. Benedetti, L. Faloppi, R. Stoico, R. Berardi
Journal: Clinical Cancer Research (2020)

Background: The coronavirus disease 2019 (COVID-19) outbreak has been declared a global pandemic, and Italyis one of the first and most heavily affected countries  Cancer patients are a population at higher risk from COVID-19 both for intrinsic fragility bound to their underlying disease and oncologic treatment delay  The aim of our survey was to investigate how cancer patients perceived their health condition, their clinical management, and informationcommunication by their medical oncologists during the pandemic  Methods: Between 15th April and 1st May, 2020, a survey was submitted to cancer patients under treatment athospitals of Marche Region that had been invested by the pandemic  It consisted of questions regarding theperception of personal safety, continuity of cancer care, and information quality provided by the OncologyDepartment and individual psychological distress  Results: A total of 661 patients participated in the survey;60 2% were female and 40 4% were aged between 46and 65  Almost all of the attendees (97 7%) stated that the Oncologic Department complied with the appropriatesafety standards, and 78% were reassured about their concerns during the medical interview, but 41% were worriedof being at higher risk of infection upon entry into the Oncology Department and 53 3% felt at greater risk of infectionbecause of chemotherapy treatment in general  The majority of the participants (62 2%) felt that postponing cancertreatment could reduce its efficacy;however, 80% declared they did not feel abandoned at the time of treatmentdelay  79 4% of the attendees felt more worried for their underlying disease in this emergency situation, but themood worsened for only 34 2% of the participants  Conclusions: Our survey reveals that Oncology Departments have been considered worthy of the emergency interms of safety standards and care management by cancer patients  However, the majority of attendees perceivedthe mutual negative influence between their underlying oncologic disease and risk of Sars-CoV-2 infection andmanifested concerns about their health condition, highlighting the need for special measures to ensure safecontinuity of care
Intermediate‐dose anticoagulation, aspirin, and in‐hospital mortality in <scp>COVID</scp>‐19: A propensity score‐matched analysis
Authors: Matthew L. Meizlish, George Goshua, Yiwen Liu, Rebecca Fine, Kejal Amin, Eric Chang, Nicholas DeFilippo, Craig Keating, Yuxin Liu, Michael Mankbadi, Dayna McManus, Stephen Y. Wang, Christina Price, Robert D. Bona, Cassius Iyad Ochoa Chaar, Hyung J. Chun, Alexander B. Pine, Henry M. Rinder, Jonathan M. Siner, Donna S. Neuberg, Kent A. Owusu, Alfred Ian Lee
Journal: American Journal of Hematology (2021)

Abstract Thrombotic complications occur at high rates in hospitalized patients with COVID‐19, yet the impact of intensive antithrombotic therapy on mortality is uncertain. We examined in‐hospital mortality with intermediate‐ compared to prophylactic‐dose anticoagulation, and separately with in‐hospital aspirin compared to no antiplatelet therapy, in a large, retrospective study of 2785 hospitalized adult COVID‐19 patients. In this analysis, we established two separate, nested cohorts of patients (a) who received intermediate‐ or prophylactic‐dose anticoagulation (“anticoagulation cohort”, N = 1624), or (b) who were not on home antiplatelet therapy and received either in‐hospital aspirin or no antiplatelet therapy (“aspirin cohort”, N = 1956). To minimize bias and adjust for confounding factors, we incorporated propensity score matching and multivariable regression utilizing various markers of illness severity and other patient‐specific covariates, yielding treatment groups with well‐balanced covariates in each cohort. The primary outcome was cumulative incidence of in‐hospital death. Among propensity score‐matched patients in the anticoagulation cohort (N = 382), in a multivariable regression model, intermediate‐ compared to prophylactic‐dose anticoagulation was associated with a significantly lower cumulative incidence of in‐hospital death (hazard ratio 0.518 [0.308–0.872]). Among propensity‐score matched patients in the aspirin cohort (N = 638), in a multivariable regression model, in‐hospital aspirin compared to no antiplatelet therapy was associated with a significantly lower cumulative incidence of in‐hospital death (hazard ratio 0.522 [0.336–0.812]). In this propensity score‐matched, observational study of COVID‐19, intermediate‐dose anticoagulation and aspirin were each associated with a lower cumulative incidence of in‐hospital death.