Multiple myeloma screening within a fracture liaison service (FLS).

Multiple myeloma (MM) remains incurable. Although early diagnosis improves outcomes, it has been unclear which populations to target for screening with serum electrophoresis, serum free light chains and urine electrophoresis. Here, we assessed the value of MM screening in a Fracture Liaison Service, finding that 1 per 195 fragility fractures has undiagnosed MM, which can be expedited to Haematology Services. PURPOSE: A key role of the Fracture Liaison Service (FLS) is screening for secondary causes of osteoporosis. In 2019, the Royal Osteoporosis Society recommended that all patients attending FLS who are recommended anti-osteoporosis therapy have universal screening for myeloma based on serum electrophoresis, serum free light chains and urine electrophoresis. Here, we examined the impact of universal myeloma screening within an FLS. METHODS: We sampled all patients seen by the Oxfordshire FLS between January and April 2018. The completion rates and outcomes of screening were checked using the hospital and FLS databases. RESULTS: Of 950 patients identified by the FLS, 628 were eligible for MM screening; 473 (75%) of these were female, and the average age was 78.4 years. Overall, 584 had some form of myeloma screening, of which 577 (92%) had serum electrophoresis, 525 (84%) had serum free light chains and 407 (65%) had urine electrophoresis measured. A total of 327 (59%) patients had complete screening. Three patients (0.5%) had newly diagnosed myeloma and were urgently referred to Haematology Services. Furthermore, 46 (8%) patients had a detectable serum paraprotein with a likely diagnosis of monoclonal gammopathy of uncertain significance (MGUS) and referred for community annual surveillance according to local guidelines. CONCLUSION: Addition of universal myeloma screening to laboratory testing identified myeloma in 1 per 195 patients, and its precursor state MGUS in 1 per 13 patients, which may have otherwise been missed. Further analysis with long-term follow-up is needed to clearly define the value of diagnosing MGUS within the FLS setting and establish the benefits vs. costs and methods to improve screening completion rates.

Changes in adult home parenteral nutrition practice over 25 years.

BACKGROUND AND AIMS: Home Parenteral Nutrition (HPN) is the established treatment of intestinal failure. This study considers the changes in practice in a single UK centre over the past twenty-five years. METHODS: Data was culled from a database used for clinical care and maintained prospectively. RESULTS: Two hundred and five patients were included from 1993 to 2018. Patient numbers increased from 22 during 1999-2003 to 158 during 2014-2018. The median age at discharge increased from 52 years during 1999-2003 to 59 years during 2014-2018. Thirty percent of patients discharged during 1999-2003 had Crohn's disease, reducing to 14% during 2014-2018. Fifteen percent of patients discharged during 1999-2003 had small bowel fistula or obstruction in comparison to 44% during 2014-2018. Only 18 patients were treated with palliative intent, the majority in recent years. An increasing number of patients required help with HPN care over the years. Survival in non-palliative patients was 85% at 1 year, 67% at 3 years, 53% at 5 years and 42% at 10 years. The majority of deaths were due to underlying disease and only 5 of 55 deaths were attributed to HPN alone. HPN dependence in non-palliative patients was 73% at 1 year, 59% at 3 years, 56% at 5 years and 43% at 10 years. Fifty eight patients stopped HPN after reconstructive surgery. Patients experienced 5.1 admissions/1000 HPN days (64.7 admission days/1000 HPN days). Admission rate did not change over the years though the percentage due to catheter problems fell from 52% to 40% while the percentage due to underlying disease or unrelated cause rose. CONCLUSIONS: The increase in numbers, age and dependency of HPN patients requires increasing resource and consideration of new models of service. Many patients with short bowel syndrome now survive to old age and the care needs of the HPN patient who has become elderly can be complex. A significant proportion of patients are being referred for HPN as a bridge to reconstructive surgery after surgical complication and this requires close involvement of gastrointestinal surgeons in HPN teams. The need for hospital admissions remains a burden for HPN patients and there is scope for changes in service provision to try to reduce hospital days.

Overview of HOMEChem: House Observations of Microbial and Environmental Chemistry.

The House Observations of Microbial and Environmental Chemistry (HOMEChem) study is a collaborative field investigation designed to probe how everyday activities influence the emissions, chemical transformations and removal of trace gases and particles in indoor air. Sequential and layered experiments in a research house included cooking, cleaning, variable occupancy, and window-opening. This paper describes the overall design of HOMEChem and presents preliminary case studies investigating the concentrations of reactive trace gases, aerosol particles, and surface films. Cooking was a large source of VOCs, CO2, NOx, and particles. By number, cooking particles were predominantly in the ultrafine mode. Organic aerosol dominated the submicron mass, and, while variable between meals and throughout the cooking process, was dominated by components of hydrocarbon character and low oxygen content, similar to cooking oil. Air exchange in the house ensured that cooking particles were present for only short periods. During unoccupied background intervals, particle concentrations were lower indoors than outdoors. The cooling coils of the house ventilation system induced cyclic changes in water soluble gases. Even during unoccupied periods, concentrations of many organic trace gases were higher indoors than outdoors, consistent with housing materials being potential sources of these compounds to the outdoor environment. Organic material accumulated on indoor surfaces, and exhibited chemical signatures similar to indoor organic aerosol.

Substrate-Independent Epitaxial Growth of the Metal-Organic Framework MOF-508a.

Plasmachemical deposition is a substrate-independent method for the conformal surface functionalization of solid substrates. Structurally well-defined pulsed plasma deposited poly(1-allylimidazole) layers provide surface imidazole linker groups for the directed liquid-phase epitaxial (layer-by-layer) growth of metal-organic frameworks (MOFs) at room temperature. For the case of microporous [Zn (benzene-1,4-dicarboxylate)-(4,4'-bipyridine)0.5] (MOF-508), the MOF-508a polymorph containing two interpenetrating crystal lattice frameworks undergoes orientated Volmer-Weber growth and displays CO2 gas capture behavior at atmospheric concentrations in proportion to the number of epitaxially grown MOF-508 layers.

Timing of palliative care team referrals for inpatients receiving rapid response services: A retrospective pilot study in a US hospital.

BACKGROUND/OBJECTIVES: Research indicates up to one-third of rapid response team calls relate to end-of-life symptoms. The CriSTAL criteria were developed as a screening tool to identify high risk of death within three months. The primary purpose of this pilot study was to investigate the timing of palliative care referrals in patients receiving rapid response team services, and patients' CriSTAL criteria score on admission. The potential feasibility of using the CriSTAL tool to stimulate earlier Palliative Care Team (PCT) referral served as an underlying goal, and investigation of a relationship between specific CriSTAL criteria and the prediction of in-hospital death was a secondary objective. DESIGN: A retrospective chart review of rapid response calls made in 2015 was used to identify patient risk of death on admission based on the CriSTAL criteria. The presence and timing of PCT referral as well as patient survival status to hospital discharge were documented for comparison. SETTING/PARTICIPANTS: A sample of 183 charts from 584 inpatients involved in over 600 RRT events recorded in 2015. The study was undertaken in a 676-bed teaching hospital in the Midwestern U.S. METHODS/RESULTS: Ninety-one patients died during the hospital stay while 92 patients from the 493 individuals who survived were randomly selected for full analysis. Applying CriSTAL criteria to the 141 individuals aged 50 years or older indicated that frailty (OR=1.43, 95%CI 1.08-1.89, p=0.012), being a male (OR=3.14; 95%CI 1.40-7.05, p=0.006), and the presence of two or more comorbidities (OR=3.71, 95%CI 1.67-8.24, p=0.001) were the most significant predictors of in-hospital death after adjusting for age. A CriSTAL score of 6 was the optimal cut-off for high-risk of in-hospital death. Palliative care consultations within the high-risk population occurred for 45.2% of the deceased and 40.4% of the survivors. Consultation often occurred within two days of the RRT event and many patients (46.8%) died within one day of the consultation. CONCLUSION: A positive relationship was found between the CriSTAL score, palliative care referral, and in-hospital mortality in patients who received RRT services. The study indicates a need for earlier PCT referral, showcases the potential to identify high risk of in-hospital death upon admission and supports the feasibility of using the CriSTAL criteria tool to encourage earlier PCT referrals.

Impaired airway epithelial cell responses from children with asthma to rhinoviral infection.

BACKGROUND: The airway epithelium forms an effective immune and physical barrier that is essential for protecting the lung from potentially harmful inhaled stimuli including viruses. Human rhinovirus (HRV) infection is a known trigger of asthma exacerbations, although the mechanism by which this occurs is not fully understood. OBJECTIVE: To explore the relationship between apoptotic, innate immune and inflammatory responses to HRV infection in airway epithelial cells (AECs) obtained from children with asthma and non-asthmatic controls. In addition, to test the hypothesis that aberrant repair of epithelium from asthmatics is further dysregulated by HRV infection. METHODS: Airway epithelial brushings were obtained from 39 asthmatic and 36 non-asthmatic children. Primary cultures were established and exposed to HRV1b and HRV14. Virus receptor number, virus replication and progeny release were determined. Epithelial cell apoptosis, IFN-ß production, inflammatory cytokine release and epithelial wound repair and proliferation were also measured. RESULTS: Virus proliferation and release was greater in airway epithelial cells from asthmatics but this was not related to the number of virus receptors. In epithelial cells from asthmatic children, virus infection dampened apoptosis, reduced IFN-ß production and increased inflammatory cytokine production. HRV1b infection also inhibited wound repair capacity of epithelial cells isolated from non-asthmatic children and exaggerated the defective repair response seen in epithelial cells from asthmatics. Addition of IFN-ß restored apoptosis, suppressed virus replication and improved repair of airway epithelial cells from asthmatics but did not reduce inflammatory cytokine production. CONCLUSIONS: Collectively, HRV infection delays repair and inhibits apoptotic processes in epithelial cells from non-asthmatic and asthmatic children. The delayed repair is further exaggerated in cells from asthmatic children and is only partially reversed by exogenous IFN-ß.

Outcome of intestinal failure after bariatric surgery: experience from a national UK referral centre.

BACKGROUND/OBJECTIVES: Bariatric surgery for morbid obesity provides sustained weight loss. Complications of bariatric surgery include severe nutritional decline, but minimal data describing occurrence and outcome of intestinal failure (IF) exist. SUBJECTS/METHODS: All patients referred to one of the UK's National IF units (IFU) are prospectively entered onto a database; case notes were assessed for bariatric surgery details, IF onset, outcomes, resulting intestinal anatomy, mortality and catheter-related bloodstream infections (CRBSIs). RESULTS: A total of six patients (mean referral age 54.0 years; 95% confidence interval (CI): 44.6-63.4; 5 female) were identified with IF after bariatric surgery from 457 patients (total cohort) managed on home parenteral nutrition (HPN) at the IFU between 2008 and 2014. In all, 6/6 had Roux-en-Y gastric bypass bariatric surgery. Median (range) time from index bariatric surgery to IF development was 28.7 months (1.7-106). IF aetiology was internal herniation (4/6), ischaemia (1/6) and anastomotic leak (1/6); all patients required HPN for a median of 26.4 months (15.3-34.7). CRBSI occurred on 7 occasions in 3 patients, equivalent to 1.5/1000 catheter days in these 6 compared with 0.32/1000 in the 451 IFU HPN patients during this time period. In all, 0/6 patients died, 6/6 had continuity restored in a median of 16.5 months (6.5-32.5) after IF diagnosis and 3/6 (50%) were weaned from PN by a median of 2.2 months (0.6-12.8). CONCLUSIONS: Bariatric surgery, an increasingly common operation, can be associated with IF necessitating long-term HPN. The cohort presented had a higher CRBSI compared with other HPN patients; more stringent approaches to catheter care may be required in this patient group, although more collective data are required.

Gastroschisis in a developing country: poor resuscitation is a more significant predictor of mortality than postnasal transfer time.

BACKGROUND: The time from birth to the first paediatric surgical consultation of neonates with gastroschisis is a predictor of mortality in dveloping countries. This is contrary to findings in the developed world. We set out to document this relationship within our population. METHOD: Neonates with gastroschisis who were transferred to Steve Biko Academic Hospital within the study period were included. The association between mortality and demographic, clinical and biochemical variables was assessed. Significant variables after univariate analysis were subjected to multivariates regression. RESULTS: Sixty patients were included. The mortality rate was 65%. Mean transfer time and distance were 14.9 hours and 225km. Forty-eight per cent of the neonates were either dehydrated or in hypovolaemic shock clinically on arrival. Eight neonates arrived hypothermic. It was shown through univariate analysis that female sex, appropriate weight for gestational age, hydration status, gestation, transfer time, serum urea, base deficit and serum bicarbonate (HCO3) were significant predictors of mortality. Only female sex, appropriate weight for gestational age and serum HC03 were shown to be significant using ultivariate analysis. CONCLUSION: Our high mortality rate was not due to lengthy transfer times. The poor clinical condition of the patients on arrival at our hospital, which relates to deficiencies in the neonatal transfer system, had a direct impact on the survival of neonates with gastroschisis.

Osteomyelitis in adult patients on long-term parenteral nutrition: 2745 patient-years of experience in a national referral centre.

BACKGROUND & AIMS: Osteomyelitis (OM) is a rare complication of catheter related sepsis after central venous catheter (CVC) use. The prevalence, characteristics and diagnosis of OM in patients with intestinal failure (IF) receiving long term parenteral nutrition (PN) through CVCs have not previously been described. METHODS: This was a retrospective study from a prospectively maintained database of patients referred to a National IF centre. Age, IF aetiology, past medical history, time on PN, OM site and organism(s) cultured were recorded. Patients were divided into 2 groups: OM occurring in the setting of acute (Type 2) IF (AIF) or chronic (Type 3) IF (CIF). Diagnosis of OM was made clinically and supported by radiological and/or microbial evidence. RESULTS: 21 cases of OM occurred in 17 patients (7 male (41%)) between 1994 and 2014. 0 cases were observed between 1994 and 1999, 1 case between 2000 and 2004, 6 cases between 2005 and 2009 and 14 cases between 2010 and 2014. There were 11 cases in 7 patients with CIF managed at the IFU between 1994 and 2014; the latter yielded a period prevalence for OM of 0.9% when compared to the 794 HPN patients managed by the IFU over this period. There were 10 cases of OM in 10 patients with AIF; patients with AIF had spent less time on PN before developing OM, compared to patients with CIF; despite this, the rate of preceding CVC infections was higher in the AIF (5.6/1000 catheter days) than in the CIF (0.3/1000 catheter days) group, as a result of patients with AIF contracting CVC infections prior to specialist referral. Patients with AIF had more severe OM compared to those with CIF, according to the Cierny Mader classification. All patients received at least 6 weeks antimicrobial chemotherapy. 4/10 (40%) AIF cases and 2/11 (18%) CIF cases required surgical intervention. No patient died from OM or its treatment. CONCLUSION: OM is a rare complication of IF and its treatment, but is being diagnosed more frequently than before and should be noted as a potential focus of sepsis in patients with IF, because it may lead to considerable morbidity.

Knowledge, group-based medical mistrust, future expectations, and perceived disadvantages of medical genetic testing: perspectives of Black African immigrants/refugees.

BACKGROUND: Reasons for low participation of ethnic minorities in genetic studies are multifactorial and often poorly understood. Based on published literature, participation in genetic testing is low among Black African immigrants/refugees although they are purported to bear disproportionate disease burden. Thus, research involving Black African immigrant/refugee populations that examine their perspectives on participating in genetic studies is needed. OBJECTIVES: This report examines and describes the knowledge of medical genetics, group-based medical mistrust, and future expectations of genetic research and the influence of these measures on the perceived disadvantages of genetic testing among Black African immigrants/refugees. METHODS: Using a cross-sectional survey design, a nonprobability sample (n = 212) of Black African immigrants/refugees was administered a questionnaire. Participants ranged in age from 18 to 61 years (mean = 38.91, SD = 9.78). The questionnaire consisted of 5 instruments: (a) sociodemographic characteristics, (b) Knowledge of Medical Genetics scale, (c) Group-Based Medical Mistrust Scale, (d) Future Expectations/Anticipated Consequences of Genetics Research scale, and (e) Perceived Disadvantages of Genetic Testing scale. RESULTS: Participants were concerned that genetic research may result in scientists 'playing God,' interfering with the natural order of life. In multivariate analyses, the perceived disadvantages of genetic testing increased as medical mistrust and anticipated negative impacts of genetic testing increased. Increase in genetic knowledge contributed to a decrease in perceived disadvantages. CONCLUSIONS: Our findings suggest that recruitment of Black African immigrants/refugees in genetic studies should address potential low knowledge of genetics, concerns about medical mistrust, the expectations/anticipated consequences of genetic research, and the perceived disadvantages of genetic testing.

The VANILLA sensor as a beam monitoring device for X-ray radiation therapy.

Cancer treatments such as intensity-modulated radiotherapy (IMRT) require increasingly complex methods to verify the accuracy and precision of the treatment delivery. In vivo dosimetry based on measurements made in an electronic portal imaging device (EPID) has been demonstrated. The distorting effect of the patient anatomy on the beam intensity means it is difficult to separate changes in patient anatomy from changes in the beam intensity profile. Alternatively, upstream detectors scatter and attenuate the beam, changing the energy spectrum of the beam, and generate contaminant radiation such as electrons. We used the VANILLA device, a Monolithic Active Pixel Sensor (MAPS), to measure the 2D beam profile of a 6 MV X-ray beam at Bristol Hospital in real-time in an upstream position to the patient without clinically significant disturbance of the beam (0.1% attenuation). MAPSs can be made very thin (~20 µm) with still a very good signal-to-noise performance. The VANILLA can reconstruct the collimated beam edge with approximately 64 µm precision.

The addition of a large caliber needle during endoscopic ultrasound-guided fine needle aspiration of solid and lymph node lesions: any importance?

AIM: The benefits of using multiple gauge needles during EUS-FNA of solid and lymph node lesions are unknown. The purpose of our study was to find out the significance of adding a large caliber needle if small caliber needle fail to achieve diagnostic specimen after few passes. METHODS: It was a retrospective review of all EUS-FNA procedures performed by one of the two experienced endosonographers. A large (22 or 19 gauge) needle was added if on-site cytologic analysis did not reveal adequate specimen after ≥2 passes. The adequacy of the specimen was determined by the Cytopathologist, and categorized as either satisfactory for analysis or unsatisfactory. The cytologic findings were reported as either benign or malignant. RESULTS: Out of total 1200 EUS cases, FNA was performed in 306 cases with different solid and lymph node lesions. Multiple gauge needles were used in 188/306 (39%) cases. There was no statistically significant difference in the diagnostic yield and definitive diagnosis between multiple and single gauge needle groups. The finding was unchanged after controlling the number of needle passes. No complications were noted. CONCLUSION: The addition of a large caliber needle achieved at least the same (or even slightly higher diagnostic yield), and can be a method of rescue in certain cases.

Evidence of endogenous volatile organic compounds as biomarkers of diseases in alveolar breath.

The effect of oxygen on markers of oxidative stress has been partially elucidated. Volatile organic compounds (VOCs) are created during the oxidative burst and excreted in the human alveolar breath, which indeed contains biomarkers. A general concept including collection, separation, detection and clinical biomakers validation is presented in this article: (i) a method for the collection and GC-MS of halogenated VOCs in human alveolar breath is described: a transportable apparatus which sampled specifically alveolar breath; the VOCs were captured in a thermal desorption tube, Carbotrap 200® and each sample was thermally desorbed from the trap in an automated GC-MS apparatus; (ii) the inhibitory effects of halogenated alkanes on mitochondria are suspected likely to fight against oxidative stress deleterious reactions; (iii) two-dimensional gas chromatography occurs by the repeated and re-injection of effluent from one chromatographic column into a second column of orthogonal phase. A new commercial GCxGC system is presented; it is accomplished with a dual-stage, quad-jet thermal modulator positioned between the two columns; (iv) the affinity-based sensors usually used in connection with the GCxGC system face a difficulty to take into account different biases coming from different sources of drifting. Compared to other affinity-based sensing modes like electrical ones, gravimetric sensors enable a better decoupling. Nano Electro Mechanical Systems (NEMS)-based resonators are a particular type of gravimetric gas sensors. They are coated with a sensitive layer of polymer where gases of interest present in the atmosphere adsorb, generating an additional mass load which is measured through a frequency shift; (v) examination of exhaled breath has the potential to change the existing routine approaches in human medicine. Breath sampling to identify volatile biomarkers in diseases has been proposed in several respiratory diseases. Several VOCs have been identified in these patients by GC-MS. However, the use of traditional analytical instruments such as GC-MS to detect biomarkers of diseases has not become a routine for clinical applications. Consequently the electronic nose was the logical instrument of choice for disease diagnosis due to the capability of identifying complex mixtures of VOCs (as a whole) within sampled air using pattern-recognition algorithms.

Whole body imaging in the diagnosis of blunt trauma, ionizing radiation hazards and residual risk.

Ever since the introduction of radiographic imaging, its utility in identifying injuries has been well documented and was incorporated in the workup of injured patients during advanced trauma life support algorithms [American College of Surgeons, 8th ed. Chicago, 2008]. More recently, computerized tomography (CT) has been shown to be more sensitive than radiography in the diagnosis of injury. Due to the increased use of CT scanning, concerns were raised regarding the associated exposure to ionizing radiation [N Engl J Med 357:2277-2284, 2007]. During the last several years, a significant amount of research has been published on this topic, most of it being incorporated in the BEIR VII Phase 2 report, published by the National Research Council of the National Academies [National Academy of Sciences, Washington DC, 2006]. The current review will analyze the scientific basis for the concerns over the ionizing radiation associated with the use of CT scanning and will examine the accuracy of the typical advanced trauma life support work-up for diagnosis of injuries.

The deubiquitination enzyme USP46 functions as a tumor suppressor by controlling PHLPP-dependent attenuation of Akt signaling in colon cancer.

PH domain leucine-rich-repeats protein phosphatase (PHLPP) is a family of Ser/Thr protein phosphatases that serve as tumor suppressors by negatively regulating Akt. Our recent studies have demonstrated that the ubiquitin proteasome pathway has an important role in the downregulation of PHLPP in colorectal cancer. In this study, we show that the deubiquitinase USP46 stabilizes the expression of both PHLPP isoforms by reducing the rate of PHLPP degradation. USP46 binds to PHLPP and directly removes the polyubiquitin chains from PHLPP in vitro and in cells. Increased USP46 expression correlates with decreased ubiquitination and upregulation of PHLPP proteins in colon cancer cells, whereas knockdown of USP46 has the opposite effect. Functionally, USP46-mediated stabilization of PHLPP and the subsequent inhibition of Akt result in a decrease in cell proliferation and tumorigenesis of colon cancer cells in vivo. Moreover, reduced USP46 protein level is found associated with poor PHLPP expression in colorectal cancer patient specimens. Taken together, these results indentify a tumor suppressor role of USP46 in promoting PHLPP expression and inhibiting Akt signaling in colon cancer.