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    A real-time electronic symptom monitoring system for patients after discharge following surgery: a pilot study in cancer-related surgery.

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    BACKGROUND Advances in peri-operative care of surgical oncology patients result in shorter hospital stays. Earlier discharge may bring benefits, but complications can occur while patients are recovering at home. Electronic patient-reported outcome (ePRO) systems may enhance remote, real-time symptom monitoring and detection of complications after hospital discharge, thereby improving patient safety and outcomes. Evidence of the effectiveness of ePRO systems in surgical oncology is lacking. This pilot study evaluated the feasibility of a real-time electronic symptom monitoring system for patients after discharge following cancer-related upper gastrointestinal surgery. METHODS A pilot study in two UK hospitals included patients who had undergone cancer-related upper gastrointestinal surgery. Participants completed the ePRO symptom-report at discharge, twice in the first week and weekly post-discharge. Symptom-report completeness, system actions, barriers to using the ePRO system and technical performance were examined. The ePRO surgery system is an online symptom-report that allows clinicians to view patient symptom-reports within hospital electronic health records and was developed as part of the eRAPID project. Clinically derived algorithms provide patients with tailored self-management advice, prompts to contact a clinician or automated clinician alerts depending on symptom severity. Interviews with participants and clinicians determined the acceptability of the ePRO system to support patients and their clinical management during recovery. RESULTS Ninety-one patients were approached, of which 40 consented to participate (27 male, mean age 64 years). Symptom-report response rates were high (range 63-100%). Of 197 ePRO completions analysed, 76 (39%) triggered self-management advice, 72 (36%) trigged advice to contact a clinician, 9 (5%) triggered a clinician alert and 40 (20%) did not require advice. Participants found the ePRO system reassuring, providing timely information and advice relevant to supporting their recovery. Clinicians regarded the system as a useful adjunct to usual care, by signposting patients to seek appropriate help and enhancing their understanding of patients' experiences during recovery. CONCLUSION Use of the ePRO system for the real-time, remote monitoring of symptoms in patients recovering from cancer-related upper gastrointestinal surgery is feasible and acceptable. A definitive randomised controlled trial is needed to evaluate the impact of the system on patients' wellbeing after hospital discharge

    Direct Skeletal Fixation in bilateral above knee amputees following blast: 2 year follow up results from the initial cohort of UK service personnel.

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    AIMS The aim of the study is to evaluate the clinical outcome and complications from the initial cohort of blast injured bilateral lower limb, above knee amputees who underwent Direct Skeletal Fixation (DSF). PATIENTS AND METHODS We undertook a retrospective analysis of a prospective data base identifying patients who had undergone implantation with the Australian Osseointegration Group of Australia-Osseointegration Prosthetic Limb (OGAP-OPL) prosthesis, with minimum 24 months follow up. Patient demographics, injury profile, and polymicrobial colonisation status were recorded. Physical functional performance measures recorded were the 6 minute Walk Test (6-MWT) and patient reported outcome measures were the Short Form Health Survey-36 (SF-36). Post operatively, complications including infection, re-operation, and fracture were recorded. RESULTS 7 patients (14 femora) were identified (mean age 29.8yrs), all injured by dismounted blast. Mean follow up was 46 months. All were polytrauma patients and all had previous polymicrobial colonisation. Following surgery, all patients mobilised with significant improvement in 6-minute walk time, with a mean improvement of 154 m (248 m vs 402 m, p = 0.018). The physical component score for the SF-36 demonstrated a statistically significant improvement from 34.65 to 54.5 (p = 0.018) and the mental component score demonstrated a similar improvement (41.55-58.19 p = 0.018). At follow up, no patient required explantation of the implant. Each had been prescribed a minimum of 1 course of antibiotics with no evidence of deep infection. CONCLUSION DSF is an option for amputees who, due to the nature of their injuries, may not be able to tolerate traditional suspension socket prostheses and have exhausted all other treatment options. At a minimum of 2 year follow up, the absence of significant infective complications suggests DSF may be utilised in the blast injured despite chronic polymicrobial colonisation. Longer term surveillance of these patients is required to assess the long-term suitability of this technique in this cohort of patients

    Discovery of Highly Selective Inhibitors of Calmodulin-Dependent Kinases That Restore Insulin Sensitivity in the Diet-Induced Obesity Mouse Model.

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    Polymorphisms in the region of the calmodulin-dependent kinase isoform D (CaMK1D) gene are associated with increased incidence of diabetes, with the most common polymorphism resulting in increased recognition by transcription factors and increased protein expression. While reducing CaMK1D expression has a potentially beneficial effect on glucose processing in human hepatocytes, there are no known selective inhibitors of CaMK1 kinases that can be used to validate or translate these findings. Here we describe the development of a series of potent, selective, and drug-like CaMK1 inhibitors that are able to provide significant free target cover in mouse models and are therefore useful as tool compounds. Our results show that a lead compound from this series improves insulin sensitivity and glucose control in the diet-induced obesity mouse model after both acute and chronic administration, providing the first validation of CaMK1D as a target for diabetes therapeutics

    Primary mesenteric sarcomas: Collaborative experience from the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

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    BACKGROUND Primary mesenteric soft tissue sarcomas (STS) are rare and limited evidence is available to inform management. Surgical resection is challenging due to the proximity of vital structures and a need to preserve enteric function. OBJECTIVES To determine the overall survival (OS) and recurrence-free survival (RFS) for patients undergoing primary resection for mesenteric STS. METHODS The Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) is an intercontinental collaborative comprising specialist sarcoma centers. Data were collected retrospectively for all patients with mesenteric STS undergoing primary resection between 2000 and 2019. RESULTS Fifty-six cases from 15 institutions were included. The spectrum of pathology was similar to the retroperitoneum, although of a higher grade. R0/R1 resection was achieved in 87%. Median OS was 56 months. OS was significantly shorter in higher-grade tumors (p = .018) and extensive resection (p < .001). No significant association between OS and resection margin or tumor size was detected. Rates of local recurrence (LR) and distant metastases (DM) at 5 years were 60% and 41%, respectively. Liver metastases were common (60%), reflecting portal drainage of the mesentery. CONCLUSION Primary mesenteric sarcoma is rare, with a modest survival rate. LR and DM are frequent events. Liver metastases are common, highlighting the need for surveillance imaging

    Cerebral perfusion and blood-brain barrier assessment in brain trauma using contrast-enhanced near-infrared spectroscopy with indocyanine green: A review.

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    Contrast-enhanced near-infrared spectroscopy (NIRS) with indocyanine green (ICG) can be a valid non-invasive, continuous, bedside neuromonitoring tool. However, its usage in moderate and severe traumatic brain injury (TBI) patients can be unprecise due to their clinical status. This review is targeted at researchers and clinicians involved in the development and application of contrast-enhanced NIRS for the care of TBI patients and can be used to design future studies. This review describes the methods developed to monitor the brain perfusion and the blood-brain barrier integrity using the changes of diffuse reflectance during the ICG passage and the results on studies in animals and humans. The limitations in accuracy of these methods when applied on TBI patients and the proposed solutions to overcome them are discussed. Finally, the analysis of relative parameters is proposed as a valid alternative over absolute values to address some current clinical needs in brain trauma care. In conclusion, care should be taken in the translation of the optical signal into absolute physiological parameters of TBI patients, as their clinical status must be taken into consideration. Discussion on where and how future studies should be directed to effectively incorporate contrast-enhanced NIRS into brain trauma care is given

    Clinical outcomes, predictors of prognosis and health economics consequences in IBD patients after discontinuation of the first biological therapy.

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    Background In real-world clinical practice, biologics in inflammatory bowel diseases (IBD) may be discontinued for a variety of reasons, including discontinuation initiated by gastroenterologists. The aims of the study are to report outcomes after discontinuation and predictors of prognosis after a minimum follow-up of 24 months; outcomes of gastroenterologist-initiated discontinuation with resulting direct cost implications on the health system were also studied. Methods IBD patients who discontinued their first-use biologics between January 2013 and December 2016 were identified at our tertiary centre. Reasons for discontinuation and pre-defined adverse outcomes (AO) were recorded. Data were analysed using univariable and multivariable logistic regressions within a machine learning technique to predict AO. Gastroenterologist-initiated discontinuations were analysed separately, and Kaplan-Meier survival analysis performed; direct costs of AO due to discontinuation were assessed. Results A total of 147 patients discontinued biologics (M = 74; median age 39 years; Crohn's Disease = 110) with median follow-up of 40 months (range 24-60 months). In the total cohort, there were fewer AO among gastroenterologist-initiated discontinuations compared with patient-initiated; 54% (of the total group) had AO within 6 months. Among 59 gastroenterologist-initiated discontinuations, 23 (40%) had IBD-related AO within 6 months and 53 (90%) patients had AO by end of follow-up. Some 44 (75%) patients needed to restart biologics during follow-up, and direct costs due to AO and restart of biologics were high. Conclusions The proportion of patients who have AO following discontinuation of biologics is high; clinicians need to carefully consider predictors of poor prognosis and high relapse rates when discussing discontinuation. The direct costs of managing AO probably offset theoretical economic gains, especially in the era where cost of biologics is reducing. Biologics should probably be continued without interruptions in most patients who have achieved remission for the duration these remain effective and safe

    Hepatocellular Carcinoma Demonstrates Heterogeneous Growth Patterns in a Multicenter Cohort of Patients With Cirrhosis.

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    BACKGROUND AND AIMS There are limited data on hepatocellular carcinoma (HCC) growth patterns, particularly in Western cohorts, despite implications for surveillance, prognosis, and treatment. Our study's aim was to quantify tumor doubling time (TDT) and identify correlates associated with indolent and rapid growth. APPROACH AND RESULTS We performed a retrospective multicenter cohort study of patients with cirrhosis diagnosed with HCC from 2008 to 2017 at six US and European health systems with two or more contrast-enhanced imaging studies performed ≥ 30 days apart prior to HCC treatment. Radiologists independently measured tumors in three dimensions to calculate TDT and specific growth rate (SGR). We used multivariable ordinal logistic regression to identify factors associated with indolent (TDT > 365 days) and rapid (TDT < 90 days) tumor growth. In the primary cohort (n = 242 patients from four centers), median TDT was 229 days (interquartile range [IQR], 89-627) and median SGR was 0.3% per day (IQR, 0.1%-0.8%). Over one-third (38%) of HCCs had indolent growth, 36.8% intermediate growth, and 25.2% rapid growth. In multivariable analysis, indolent growth was associated with larger tumor diameter (odds ratio [OR], 1.15, 95% confidence interval [CI], 1.03-1.30) and alpha-fetoprotein < 20 ng/mL (OR, 1.90; 95% CI, 1.12-3.21). Indolent growth was more common in nonviral than viral cirrhosis (50.9% versus 32.1%), particularly in patients with T1 HCC (OR, 3.41; 95% CI, 1.08-10.80). Median TDT (169 days; IQR 74-408 days) and SGR (0.4% per day) were similar in an independent cohort (n = 176 patients from two centers). CONCLUSIONS In a large Western cohort of patients with HCC, we found heterogeneous tumor growth patterns, with one-fourth exhibiting rapid growth and over one-third having indolent growth. Better understanding different tumor growth patterns may facilitate a precision approach to prognostication and treatment

    Habitual scratching amplifies and perpetuates atopic dermatitis.

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    We were fascinated and heartened to read this very helpful commentary1 on the study by Redhu et al2 who describe some precise physico-biological pathways that link skin barrier disruption to itch in atopic dermatitis (AD). This may well explain how curtailing scratching in AD with the simple behavioural technique of habit reversal can so dramatically improve the condition3. It is important to note that scratching in AD over time often becomes not only a response to itch, but also to both habit and mental state

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