Monitoring complex endocrine pathways is often limited by indirect measurement or measurement of a single hormone class per analysis. There is a burgeoning need to develop specific direct-detection ...methods capable of providing simultaneous measurement of biologically relevant concentrations of multiple classes of hormones (estrogens, androgens, progestogens, and corticosteroids). The objectives of this study were to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for multi-class steroid hormone detection using biologically relevant concentrations, then test limits of detection (LOD) in a high-background matrix by spiking charcoal-stripped fetal bovine serum (FBS) extract. Accuracy was tested with National Institute of Standards and Technology Standard Reference Materials (SRMs) with certified concentrations of cortisol, testosterone, and progesterone. 11-Deoxycorticosterone, 11-deoxycortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, adrenosterone, androstenedione, cortisol, corticosterone, dehydroepiandrosterone, dihydrotestosterone, estradiol, estriol, estrone, equilin, pregnenolone, progesterone, and testosterone were also measured using isotopic dilution. Dansyl chloride (DC) derivatization was investigated maintaining the same method to improve and expedite estrogen analysis. Biologically relevant LODs were determined for 15 hormones. DC derivatization improved estrogen response two- to eight-fold, and improved chromatographic separation. All measurements had an accuracy ≤14 % difference from certified values (not accounting for uncertainty) and relative standard deviation ≤14 %. This method chromatographically separated and quantified biologically relevant concentrations of four hormone classes using highly specific fragmentation patterns and measured certified values of hormones that were previously split into three separate chromatographic methods.
Unrecognized clinical deterioration is a common and significant source of preventable harm to hospitalized children. Yet, unlike other sources of preventable harm, clinical deterioration outside of ...the ICU lacks a clear, “gold standard” outcome to guide prevention efforts. This gap limits multicenter learning, which is crucial for identifying effective and generalizable interventions for harm prevention. In fact, to date, no coordinated safety/quality initiative currently exists targeting prevention of harm from unrecognized clinical deterioration in hospitalized pediatric patients, which is startling given the morbidity and mortality risk patients incur. In this article, we compare existing outcomes for evaluating clinical deterioration outside of the ICU, highlighting sources of variation and vulnerability. The broader aim of this article is to highlight the need for a standard, consensus outcome for evaluating clinical deterioration outside of the ICU, which is a critical first step to preventing this type of harm.
Summary
Background
All organ transplant populations are predisposed to increased rates of keratinocyte carcinoma (KC). Since this increased risk was first appreciated, immunosuppressive regimens have ...changed and organ transplant recipients (OTRs) have been aggressively screened for KC. There is a perception that these measures have impacted on KC incidence but there is a paucity of population‐based studies on post‐transplant rates of basal cell carcinoma (BCC).
Objectives
To identify trends in incidence rates for KC following solid organ transplantation over the past two decades.
Methods
This nationwide, population‐based study included all solid OTRs transplanted between 1994 and 2014. Patient data were matched to national cancer registry data to determine the standardized incidence ratio (SIR) of KC in solid OTRs compared with the general population.
Results
In total 3580 solid OTRs were included. The total follow‐up time was 28 407 person‐years (median follow‐up 7·11 years). The overall SIRs for squamous cell carcinoma (SCC) and BCC were 19·7 and 7·0, respectively. Our study documents a progressive fall in the SIRs for SCC and BCC from peak SIRs (95% confidence intervals) in 1994–1996 of 26·4 (21·5–32·4) and 9·1 (7·4–11·3) to 6·3 (2·3–16·7) and 3·2 (1·4–7·1) in 2012–2014, respectively. The ratio of SCC to BCC has remained at 3 to 1 over the last two decades.
Conclusions
Our study is the first to demonstrate a significant reduction over the past two decades in the incidences of both SCC and BCC following solid organ transplantation. The SCC‐to‐BCC ratio was maintained, demonstrating that both are reducing equally. This trend coincided with temporal changes in immunosuppressive protocols and the introduction of skin cancer prevention programmes.
What's already known about this topic?
Prior studies have shown that the risk of cutaneous squamous cell carcinoma (SCC) has declined over recent decades following solid organ transplantation.
It is not known whether the risk of basal cell carcinoma (BCC) has reduced in line with this.
What does this study add?
Our study documents a progressive fall in the risk of SCC and BCC following solid organ transplantation over the last two decades.
The SCC‐to‐BCC ratio was maintained, demonstrating that both are reducing equally.
The trends observed in our study coincided with temporal changes in immunosuppressive protocols and the introduction of cancer prevention programmes, suggesting that these factors have positively impacted on the risk of keratinocyte carcinoma in this cohort.
Linked Editorial: Gjersvik. Br J Dermatol 2019; 181:879–880
Plain language summary available online
Respond to this article
The organic food market’s recent rapid global growth reflects the public’s interest in buying certified organic foods, including packaged products. Our analysis shows that packaged foods containing ...fewer ingredients associated with negative public health outcomes are more likely to be labeled organic. Previous studies comparing organic and conventional foods focused primarily on nutrient composition. We expanded this research by additionally examining ingredient characteristics, including processing and functional use. Our dataset included nutrition and ingredient data for 8240 organic and 72,205 conventional food products sold in the U.S. from 2019 to 2020. Compared to conventional foods, organic foods in this dataset had lower total sugar, added sugar, saturated fat and sodium content. Using a mixed effects logistic regression, we found that likelihood of classification as organic increased as sodium content, added sugar content and the number of ultra-processed ingredients and cosmetic additives on the product label decreased. Products containing no trans-fat ingredients were more likely to be labeled organic. A product was more likely to be classified “organic” the more potassium it contained. These features of organic foods sold in the U.S. are significant because lower dietary ingestion of ultra-processed foods, added sugar, sodium and trans-fats is associated with improved public health outcomes.
Essentials
Eisenmenger syndrome is characterised by thrombotic and hemorrhagic risks of unclear aetiology.
Calibrated automated thrombography was used to assess these coagulation derangements.
...Platelet activity supported abnormalities in procoagulant and anticoagulant pathway function.
Endothelin‐1 antagonism appeared to ameliorate these derangements.
Summary
Aims
The mechanisms underlying the competing thrombotic and hemorrhagic risks in Eisenmenger syndrome are poorly understood. We aimed to characterize derangements of blood coagulation and to assess the effect of dual endothelin‐1 receptor antagonism in modulating hemostasis in this rare disorder.
Methods
In a 10‐month recruitment period at a tertiary cardiology referral center, during which time there were over 14 000 outpatient consultations, consecutive subjects with Eisenmenger syndrome being considered for macitentan therapy (n = 9) and healthy volunteers (n = 9) were recruited. Plasma thrombin generation in platelet‐rich and platelet‐poor plasma was assessed by calibrated automated thrombography prior to and following therapy.
Results
Median peak plasma thrombin generation was higher in platelet‐rich plasma obtained from Eisenmenger syndrome subjects relative to controls (median peak thrombin 25th–75th percentile: 228.3 206.5–258.6 nm vs. 169.9 164.3–215.8 nm), suggesting a critical mechanistic role for platelets in supporting abnormal hypercoagulability in Eisenmenger syndrome. Abnormal enhanced sensitivity to the anticoagulant activity of activated protein C was also observed in platelet‐rich plasma in Eisenmenger syndrome, suggesting that derangements of platelet activity may influence the activity of anticoagulant pathways in a manner that might promote bleeding in this disease state. Following 6 months of macitentan therapy, attenuations in the derangements in both procoagulant and anticoagulant pathways were observed.
Conclusions
Abnormal platelet activity contributes to derangements in procoagulant and anticoagulant pathways in Eisenmenger syndrome. Therapies targeting the underlying vascular pathology appear to ameliorate these derangements and may represent a novel strategy for the management of the competing prothrombotic and hemorrhagic tendencies in this disorder.
Proactive surveillance by a critical care outreach team (CCOT) can promote early recognition of deterioration in hospitalized patients but is uncommon in pediatric rapid response systems (RRSs). ...After our children’s hospital introduced a CCOT in 2019, we aimed to characterize early implementation outcomes. We hypothesized that CCOT rounding would identify additional children at risk for deterioration.
The CCOT, staffed by a dedicated critical care nurse (RN), respiratory therapist, and attending, conducts daily in-person rounds with charge RNs on medical-surgical units, to screen RRS-identified high-risk patients for deterioration. In this prospective study, observers tracked rounds discussion content, participation, and identification of new high-risk patients. We compared ‘identified-patient-discussions’ (IPD) about RRS-identified patients, and ‘new-patient-discussions’ (NPD) about new patients with Fisher’s exact test. For new patients, we performed thematic analysis of clinical data to identify deterioration related themes.
During 348 unit-rounds over 20 days, we observed 383 discussions − 35 (9%) were NPD. Frequent topics were screening for clinical concerns (374/383, 98%), active clinical concerns (147/383, 39%), and watcher activation (66/383, 17%). Most discussions only included standard participants (353/383, 92%). Compared to IPD, NPD more often addressed active concerns (74.3% vs 34.8%, p < 0.01) and staffing resource concerns (5.7% vs 0.6%, p < 0.04), and more often incorporated extra participants (25.7% vs 6%, p < 0.01). In thematic analysis of 33 new patients, most (29/33, 88%) had features of deterioration.
A successfully implemented CCOT enhanced identification of clinical deterioration not captured by existing RRS resources. Future work will investigate its impact on operational safety and patient-centered outcomes.
Summary
Intrathecal morphine is an analgesic option for major hepatopancreaticobiliary procedures but is associated with a risk of respiratory depression. We hypothesised that a postoperative ...low‐dose naloxone infusion would reduce the incidence of respiratory depression without an increase in pain scores. Patients scheduled for major open hepatopancreaticobiliary surgery and who were receiving 10 μg.kg−1 intrathecal morphine were eligible for inclusion. Patients were allocated randomly to receive a postoperative infusion of naloxone 5 μg.kg−1.h−1 (naloxone group) or saline at an identical infusion rate (control group) until the morning after surgery. Clinicians, nursing staff and patients were blinded to group allocation. The primary outcome measure was the incidence of respiratory depression (respiratory rate < 10 breaths.min−1 and/or oxygen saturation < 90%). Secondary outcome measures included: arterial partial pressure of carbon dioxide; pain score; requirement for supplemental analgesic; and incidence of nausea and vomiting, pruritus and sedation. In total, data from 95 patients (48 in the naloxone group and 47 in the control group) were analysed. The incidence of respiratory depression was lower in the naloxone group compared with the control group (10/48 vs. 21/47 patients, respectively; p = 0.037, relative risk 0.47 (95%CI 0.25–0.87). Maximum pain scores were greater for patients allocated to the naloxone group compared with control (median 5 (95%CI 4–6) vs. 4 (95%CI 2–4), respectively; p < 0.001). A low‐dose naloxone infusion decreases the incidence of respiratory depression following intrathecal morphine administration in patients having major hepatopancreaticobiliary surgery at the expense of a small increase in postoperative pain.
Keratinocyte carcinoma in organ transplant recipients Menzies, S.; O'Leary, E.; Callaghan, G. ...
British journal of dermatology (1951),
November 2019, 2019-11-00, 20191101, Letnik:
181, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Summary
Skin cancer commonly affects people who have received a solid organ transplant (heart, lung, liver and kidney). Transplant patients can get multiple skin cancers, some of which can grow very ...quickly. The commonest types of skin cancer are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Immunosuppressant medication is used to prevent rejection of the transplanted organ. This alters the body's immune system, which in turn means that transplant patients are more prone to skin cancers that can grow rapidly. Over the last 20 years, newer immunosuppressants have been introduced which are thought to lessen the risk of skin cancer. Previous studies have shown a lower risk of SCC with the newer medication, but no study to date has looked at BCC rates. This study, from Ireland, aimed to find out if the rate of skin cancer in transplant patients has reduced over the last 20 years, spanning the introduction of newer immunosuppressive medications. The National Cancer Registry of Ireland registers all skin cancers for the Republic of Ireland. The authors looked at the rate of skin cancer in people who received a solid organ transplant and compared this to the rate of skin cancer in the general population. They found that the rate of SCC and BCC in patients who received an organ transplant has significantly reduced over the last two decades. This change in risk of skin cancer coincided with changes in immunosuppressant medication, along with focused education and regular skin cancer screening for transplant recipients.
Linked Article: Menzies et al. Br J Dermatol 2019; 181:983–991
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