Validation of HIV-infected cohort identification using automated clinical data in the Department of Veterans Affairs.

OBJECTIVES: The US Department of Veterans Affairs (VA) is the largest integrated health care provider for HIV-infected patients in the USA. VA data for HIV-specific clinical and quality improvement research are an important resource. We sought to determine the accuracy of using the VA Corporate Data Warehouse (CDW), a fully automated medical records database for all VA users nationally, to identify HIV-infected patients compared with a gold-standard VA HIV Clinical Case Registry (CCR). METHODS: We assessed the test performance characteristics of each of our CDW criteria-based algorithms (presence of one, two or all of the following: diagnostic codes for HIV, positive HIV laboratory tests, and prescription for HIV medication) by calculating their sensitivity (proportion of HIV-positive patients in the CCR accurately detected as HIV-positive by the CDW algorithm) and positive predictive value (PPV; the proportion of patients identified by the CDW algorithm who were classified as HIV-positive from the CCR). RESULTS: We found that using a CDW algorithm requiring two of three HIV diagnostic criteria yielded the highest sensitivity (95.2%) with very little trade-off in PPV (93.5%). CONCLUSIONS: A two diagnostic criteria-based algorithm can be utilized to accurately identify HIV-infected cohorts seen in the nationwide VA health care system.

Ixazomib-induced cutaneous necrotizing vasculitis.

Ixazomib is a second-generation proteasome inhibitor that has been approved in the combination treatment of multiple myeloma and is currently under clinical investigation for the management of Waldenstrom's macroglobulinemia. While cutaneous adverse events secondary to proteasome inhibitors have been reported, the side effect profile of ixazomib remains to be documented. We report two patients, one with multiple myeloma and one with Waldenstrom's macroglobulinemia, who developed cutaneous necrotizing vasculitis after the initiation of ixazomib. Both patients exhibited no signs of systemic vasculitis and completed their anti-cancer regimens with resolution of their respective eruptions following dose reductions in ixazomib and initiation of low-dose prednisone. A collaborative effort towards the characterization of such cutaneous toxicities facilitates early intervention, maintenance of life-preserving anti-cancer therapy, and allows clinicians opportunity to better understand the pathophysiology of vasculitis. Moreover, appropriate identification and characterization of cutaneous toxicities from novel therapies allows providers to accurately identify safety concerns, treat toxicity, and improve patient quality of life.

Can acoustic radiation force imaging of the liver and spleen predict the presence of gastroesophageal varices?

AIM: To determine whether acoustic radiation force imaging (ARFI) of the liver/spleen could be used in patients with cirrhosis to predict the presence of gastroesophageal varices (GOVs). MATERIALS AND METHODS: Fifty-eight patients with cirrhosis who were undergoing 6-monthly ultrasound examinations for hepatoma surveillance and who were due to have oesophagogastroduodenoscopy (OGD) within 6 months of their ultrasound were recruited. During routine ultrasound, the patient's liver and spleen were also assessed using ARFI. Other clinical parameters (platelet count, spleen size, and transient elastography measurements) were also collected. Logistic regression was used to determine which variables were significantly associated with presence or absence of varices univariably and multivariably RESULTS: Fourteen patients (24%) had GOVs. Patients with GOVs had higher ARFI measurements in the liver and spleen than patients without GOVs (liver: 2.39 versus 2.13, spleen: 2.89 versus 2.82), but these results were not statistically significant (odds ratio=1.75, 95% confidence interval [CI]=0.82, 3.91 and odds ratio=1.12, 95% CI=0.33, 3.97, respectively). The platelet/splenic ratio, in comparison, was associated with the presence or absence of GOVs in multivariate analysis (odds ratio=0.32, 95% CI=0.008, 0.91). CONCLUSION: Although patients with GOVs had overall higher ARFI liver and spleen results, this was not statistically significant. As such, ARFI cannot yet replace OGD in predicting GOVs in this patient group.

Second primary malignancies in multiple myeloma: an overview and IMWG consensus.

Background: Therapeutic advancements following the introduction of autologous stem cell transplantation and 'novel' agents have significantly improved clinical outcomes for patients with multiple myeloma (MM). Increased life expectancy, however, has led to renewed concerns about the long-term risk of second primary malignancies (SPMs). This review outlines the most up-to-date knowledge of possible host-, disease-, and treatment-related risk factors for the development of SPMs in patients with MM, and provides practical recommendations to assist physicians. Design: A Panel of International Myeloma Working Group members reviewed the most relevant data published in the literature as full papers, or presented at meetings of the American Society of Clinical Oncology, American Society of Hematology, European Hematology Association, or International Myeloma Workshops, up to June 2016. Here, we present the recommendations of the Panel, based on this literature review. Results: Overall, the risk of SPMs in MM is low, multifactorial, and partially related to the length of patients' survival and MM intrinsic susceptibility. Studies suggest a significantly increased incidence of SPMs when lenalidomide is administered either following, or concurrently with, oral melphalan. Increased SPM incidence has also been reported with lenalidomide maintenance following high-dose melphalan, albeit to a lesser degree. In both cases, the risk of death from MM was significantly higher than the risk of death from SPMs, with lenalidomide possibly providing a survival benefit. No increase in SPM incidence was reported with lenalidomide plus dexamethasone (without melphalan), or with bortezomib plus oral melphalan, dexamethasone, or thalidomide. Conclusion: In general, the risk of SPMs should not alter the current therapeutic decision-making process in MM. However, regimens such as lenalidomide plus dexamethasone should be preferred to prolonged exposure to lenalidomide plus oral melphalan. SPM risk should be carefully discussed with the patient in the context of benefits and risks of different treatment options.

Ultrasound surveillance for hepatocellular carcinoma: service evaluation of a radiology-led recall system in a tertiary-referral centre for liver diseases in the UK.

AIM: To review the radiology-led ultrasound (US) surveillance programme for the detection of hepatocellular carcinoma (HCC) in cirrhotic patients in a UK tertiary-referral centre. MATERIALS AND METHODS: The radiology information system was searched for patients who had undergone US for surveillance of cirrhosis from September 2009 to May 2013. Patient demographics and cirrhosis aetiology were documented. Data including numbers of surveillance scans, abnormal findings suspicious for HCC, subsequent radiological investigations, numbers of HCC and survival for HCC patients were recorded. Service performance data, such as rates of attendance and rebooking, were also recorded. RESULTS: Eight hundred and four patients entered surveillance and 2,366 surveillance US examinations were performed; 368 (46%) underwent follow-up (6-monthly US). Abnormalities leading to further radiological investigations were found in 81 patients. Reasons for incomplete surveillance included non-attendance and radiology failure to re-book appointments. HCC was diagnosed in 22 patients. Fourteen had HCC diagnosed on a surveillance scan, eight had HCC diagnosed on a scan performed for other reasons. Patients diagnosed with HCC on a surveillance scan were more likely to be treated with curative intent and had longer survival. CONCLUSION: Even with a radiology-led recall service for HCC surveillance, the proportion of patients receiving scans 6-monthly was low, due in part to the lack of organisational support that is available for other screening programmes. This study gives a realistic representation of the implementation of surveillance in a UK hospital at the current time and of the rates of HCC proceeding to treatment.

Exercise-induced improvements in liver fat and endothelial function are not sustained 12 months following cessation of exercise supervision in nonalcoholic fatty liver disease.

Supervised exercise reduces liver fat and improves endothelial function, a surrogate of cardiovascular disease (CVD) risk, in nonalcoholic fatty liver disease (NAFLD). We hypothesised that after a 16-week supervised exercise program, patients would maintain longer-term improvements in cardiorespiratory fitness, liver fat and endothelial function. Ten NAFLD patients (5/5 males/females, age 51±13 years, body mass index 31±3 kg m-2 (mean±s.d.)) underwent a 16-week supervised moderate-intensity exercise intervention. Biochemical markers, cardiorespiratory fitness (VO2peak), subcutaneous, visceral and liver fat (measured by magnetic resonance imaging and spectroscopy respectively) and brachial artery flow-mediated dilation (FMD) were assessed at baseline, after 16 weeks of supervised training and 12 months after ending supervision. Despite no significant change in body weight, there were significant improvements in VO2peak (6.5 ml kg-1 min-1 (95% confidence interval 2.8, 10.1); P=0.003), FMD (2.9% (1.5, 4.2); P=0.001), liver transaminases (P<0.05) and liver fat (-10.1% (-20.6, 0.5); P=0.048) immediately after the 16-week supervised training. Nevertheless, 12 months after ending supervision, VO2peak (0.9 ml kg-1 min-1 (-3.3, 5.1); P=0.65), FMD (-0.07% (-2.3, 2.2); P=0.95), liver transaminases (P>0.05) and liver fat (1.4% (-13.0, 15.9); P=0.83) were not significantly different from baseline. At 12 months following cessation of supervision, exercise-mediated improvements in liver fat and other cardiometabolic variables had reversed with cardiorespiratory fitness at baseline levels. Maintenance of high cardiorespiratory fitness and stability of body weight are critical public health considerations for the treatment of NAFLD (Clinicaltrials.gov identifier: NCT01834300).

Development of a conceptual model to illustrate the impact of multiple myeloma and its treatment on health-related quality of life.

PURPOSE: Little qualitative research exploring the impact of multiple myeloma (MM) and its treatment on the health-related quality of life (HRQL) of patients has been published. This study aimed to explore the burden of MM symptoms and treatment and the impact of these on HRQL. A model was developed to illustrate key concepts and their interrelationships. METHODS: Patients with MM were recruited to this cross-sectional, qualitative study through a patient panel and at two clinical sites in the USA. An interview discussion guide was developed using a review of published literature and interviews with experienced MM clinicians. In-depth, semistructured telephone interviews with MM patients were conducted to explore their experiences of the disease and its treatment. Data were analyzed using a thematic analysis approach. RESULTS: Twenty MM patients at various stages of treatment participated in open-ended, semistructured interviews. Patients reported both current and previous MM symptoms; most had experienced fatigue and pain. Other commonly reported symptoms were fractures, anemia, neuropathy, aches, and infections. MM treatment was found to have a negative impact on patients' HRQL; treatment-related adverse events included fatigue, neuropathy, insomnia, and gastrointestinal symptoms. MM treatment placed a substantial psychological and physical burden on patients, disrupting social activities, decreasing independence, and impacting on relationships. A model was developed to illustrate the relationship between these concepts. CONCLUSION: The conceptual model developed in this study illustrates the many aspects of MM and its treatment and how they can have a negative impact on patients' HRQL.

NMR T1 relaxation time measurements and calculations with translational and rotational components for liquid electrolytes containing LiBF4 and propylene carbonate.

Longitudinal relaxation (T1) measurements of (19)F, (7)Li, and (1)H in propylene carbonate/LiBF4 liquid electrolytes are reported. Comparison of T1 values with those for the transverse relaxation time (T2) confirm that the measurements are in the high temperature (low correlation time) limit of the T1 minimum. Using data from pulsed field gradient measurements of self-diffusion coefficients and measurements of solution viscosity measured elsewhere, it is concluded that although in general there are contributions to T1 from both translational and rotational motions. For the lithium ions, this is mainly translational, and for the fluorine ions mainly rotational.

Root and Stem Rot of Begonia Caused by Phytopythium helicoides in Virginia.

In the summer of 2011, severe root and stem rot of begonia (Begonia × semperflorens-cultorum cv. Vodka Dark Red) was observed during a field trial. Seventy-eight percent of the plants had symptoms included foliar blight, blackened and rotting roots, rotting stems, and collapsing crown, often leading to plant death. Isolation from the diseased plant roots consistently recovered a Pythium-like species and 41 isolates were subcultured for identification. These isolates produced very similar single-strand conformation polymorphism (SSCP) fingerprints (2), which were distinct from those of other oomycete pathogens known to attack begonia (1). These isolates produced proliferous, ovoid to globose, terminal, and papillate sporangia which were 30.6 to 45.4 µm (av. 38.7 µm) in length and 20.5 to 35.4 µm (av. 28.2 µm) in width. Oogonia were produced in single culture grown in clarified V8 juice agar. These smooth-walled oogonia were mostly aplerotic and 28.9 to 36.8 µm (av. 33.1 µm) in diameter. Each contained a single oospore with a diameter of 23.7 to 34.4 µm (av. 26.9 µm). Single to multiple antheridia were attached lengthwise to each oogonium. These morphological characteristics match the description of Phytopythium helicoides (= Pythium helicoides) (3). The identity of these isolates was confirmed by sequencing the rDNA internal transcribed spacer (ITS) 1 and 2 regions. ITS sequence of the representative isolate 55C7 (GenBank Accession No. KC907734) had 97 to 99% homology with P. helicoides sequences in GenBank. Two isolates, 55C7 and 56A7, were tested for pathogenicity to begonia in the summer of 2012. Twelve plants per isolate were inoculated by injecting ground P. helicoides-colonized rice grains into the root soil using a long-neck funnel. Sterile rice grains were used on control plants. Aboveground symptoms including foliar blight, stem rot, and collapsing crown were observed 7 days after inoculation and the disease progressed for additional 6 weeks. At 7 weeks, all inoculated plants showed different symptom levels. Four and 10 plants inoculated with 55C7 and 56A7, respectively, were already dead. Begonia roots showed severe symptoms including blackening, stunted growth, and rotting. Seven of 12 control plants also had notable symptoms due to cross contamination. Isolates recovered from all symptomatic plants had identical SSCP fingerprints to those of isolates 55C7 and 56A7. To our knowledge, this is the first report of P. helicoides attacking begonia plants. The avenue of this pathogen entering the 2011 field trial remains unknown. The field trial in 2011 and pathogenicity test in 2012 indicate that this pathogen is potentially destructive to begonia. Additional research is warranted to identify the origin and dissemination of this pathogen to mitigate the risk to begonia production. References: (1) C. X. Hong et al. Plant Dis. 92: 1201, 2008. (2) P. Kong et al. FEMS Microbiol. Lett. 240:229, 2003. (3) A. J. van der Plaats-Niterink. Monograph of the Genus Pythium. Centraalbureau voor Schimmelcultures, Baarn, the Netherlands, 1981.

Secretory phospholipase Pla2g2a confers resistance to intestinal tumorigenesis.

Individuals inheriting the same mutation predisposing to cancer may show very different outcomes, ranging from early aggressive cancer to disease-free survival. Experimental mouse models can provide a powerful tool to identify factors in the environment and genetic background that account for such modifications. The Min mouse strain, in which the ApcMin mutation disrupts the mouse homologue of the human familial polyposis gene, develops intestinal neoplasms whose multiplicity is strongly affected by genetic background. We previously mapped a strong modifier locus, Mom1 (modifier of Min-1), to a 4-cM region on mouse chromosome 4 containing a candidate gene Pla2g2a encoding a secretory phospholipase. Here, we report that a cosmid transgene overexpressing Pla2g2a caused a reduction in tumour multiplicity and size, comparable to that conferred by a single copy of the resistance allele of Mom1. These results offer strong evidence that this secretory phospholipase can provide active tumour resistance. The association of Pla2g2a with Mom1 thus withstands a strong functional test and is likely to represent the successful identification of a polymorphic quantitative trait locus in mammals.

Smoking prevalence amongst UK Armed Forces recruits: changes in behaviour after 3 years follow-up and factors affecting smoking behaviour.

OBJECTIVES: The purpose of this study was to investigate smoking prevalence of Tri-Service recruits, and changes in smoking behaviour at 3-year follow-up, by trade group and gender. Associations with educational attainment and deprivation were also assessed. METHODS: Analysis of a survey into the health behaviours of 10 531 recruits in 1998/1999. A follow-up 3 years later measured changes in behaviour. Correlation and multiple regression was used to investigate the relationship between smoking prevalence in each trade group and both educational attainment and deprivation, using Index of Multiple Deprivation 2004 (IMD 2004) scores. RESULTS: Army recruits exhibited a significantly higher smoking prevalence (45%) than Royal Navy recruits (34%) and Royal Air Force (RAF) recruits (31%). There were marked differences between smoking levels amongst officer cadets (12%, 20% and 10% in the Navy, Army and RAF, respectively) and other rank trade groups (24-56%), with the exception of the Marines (13%). At follow up, smoking had generally increased, and in some parts of the infantry had risen to 66%. There was a clear correlation between smoking at enlistment and both educational attainment (correlation coefficient=0.7, p<0.005) and deprivation score (correlation coefficient=0.8, p<0.005). CONCLUSIONS: There were clear differences between Services, rank and trade groups in smoking prevalence at recruitment. Smoking levels increased in the 3 years after recruitment to the Armed Forces. Deprivation was more important than educational attainment in determining the smoking status of recruits.

Pulmonary function over 2 years in diabetic patients treated with prandial inhaled Technosphere Insulin or usual antidiabetes treatment: a randomized trial.

AIMS: Development of inhaled insulin has increased the need to understand its pulmonary safety. This study evaluated pulmonary function changes in diabetes patients receiving inhaled Technosphere Insulin (TI) or usual antidiabetes treatment (usual care). METHODS: This randomized, open-label study was conducted at 220 sites (25 July 2005 to 29 August 2008). Pulmonary function tests [forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), total lung capacity (TLC) and lung diffusion capacity for carbon monoxide (DL(CO))] were prospectively followed over 2 years in patients with type 1 or type 2 diabetes receiving TI (n = 730) or usual care (n = 824), along with a cohort without diabetes not receiving any specific therapy (n = 145). RESULTS: Baseline demographics and pulmonary function were similar between diabetes treatment groups. Lung function declined from baseline in all groups. TI was non-inferior to usual care for mean change in FEV(1) from baseline to month 24 [mean (s.e.m.) 0.037 (0.0119) l; 95% CI 0.014 to 0.060] using mixed-model repeated-measure with a pre-specified non-inferiority margin of 50 ml/year. After a greater initial decline at month 3 with TI, rate of change (slope) in FEV(1), FVC and DL(CO) (months 3-24) was not statistically different between treatment groups. TI was well tolerated; no serious safety concerns emerged. The most common respiratory event associated with TI was mild, transient cough, occurring within minutes of inhalation. CONCLUSIONS: Observed changes in lung function with TI were small, occurred early after therapy initiation, remained non-progressive over 2 years and were unlikely to be clinically meaningful.

Epidural catheter connectors: a laboratory-based comparison of the Portex Tuohy-Borst and EpiFuse™ designs.

Disconnection of an epidural catheter from its connector may result in patient harm and commonly requires resiting of the epidural. Clamp-connector designs such as the novel Portex EpiFuse™ potentially offer an improved safety profile over screw-cap designs such as the Tuohy-Borst, but comparative studies are limited. We therefore compared the tensile strength of EpiFuse and Tuohy-Borst connectors in a laboratory setting. We further sought to establish whether operator modification of the EpiFuse increased its vulnerability to disconnection. The median (IQR [range]) force to induce disconnection was 8.0 (4.1-12.8 [0.0-22.6]) N for Tuohy-Borst connectors and 16.4 (15.2-17.7 [5.7-18.9]) and 15.9 (15.0-16.9 [5.8-18.1]) N for standard and modified EpiFuse connectors, respectively (p<0.0001). The Tuohy-Borst was also less likely to meet British Standard requirements (13/20 sets vs 19/20 and 20/20, p=0.002). Modification of the EpiFuse did not affect lumen patency or connection strength. We conclude that under controlled conditions, EpiFuse connectors are superior to Tuohy-Borst connectors.

Phytophthora hedraiandra Detected from Irrigation Water at a Perennial Ornamental Plant Nursery in Virginia.

Water survey for Phytophthora spp. by baiting with rhododendron leaves in April 2006 at a perennial ornamental plant nursery in Virginia detected five isolates showing a unique, previously unknown single-strand conformation polymorphism (SSCP) fingerprint (1). These cultures were isolated from two reservoirs at different depths of water column from surface to 2 m. They were homothallic and produced smooth-surfaced spherical oogonia with an average diameter of 27 µm on 10% V8 agar. Oospores were aplerotic. The paragynous antheridia were averaging 12 µm in diameter. Sporangia were papillate, spherical to ovoid, averaging 39 by 28 µm (length by width). They were caducous with short (<4 µm) pedicels. Chlamydospores and hyphal swellings were not observed. Two isolates were sequenced for rDNA internal transcribed spacer (ITS) 1 and 2 regions and cytochrome oxidase subunit 1 (Cox 1) gene. ITS sequences of both isolates (GenBank Accession Nos. JN376065 and JN376066) were identical to that of Phytophthora hedraiandra type culture (GenBank Accession No. AY707987). Also, the Cox 1 sequence of an isolate (Accession No. JN376067) had 99% homology with that of the type culture (GenBank Accession No. AY69115). Pathogenicity of both isolates was tested on Rhododendron catawbiense and Viburnum tinus, two known hosts of P. hedraiandra (2). For each isolate and host, five leaves and stems on potted plants were wounded by needles and then inoculated by placing over each wound a 5-mm2 mycelial plug from a 7-day-old culture and securing with Parafilm. V8 agar was used instead of mycelial plugs on control plants. After inoculation, each plant was enclosed in a plastic bag for 1 day and then incubated at 22°C with a 12-h photoperiod. Distilled water was sprayed daily for 5 days postinoculation (dpi) until disease symptoms were observed. At 15 dpi, 3 of the 10 inoculated rhododendron leaves and 6 of the 10 stems showed leaf lesions, wilting, dieback, and cankers, eventually leading to rhododendron death. Two of the 10 viburnum leaves and 4 of the 10 stems showed similar symptoms. Leaf lesions were approximately 3 to 5 cm in diameter. P. hedraiandra was recovered from diseased tissues and all resulting cultures showed an identical SSCP fingerprint to tested isolates as well as a P. hedraiandra isolate from Minnesota (3). No symptom developed on control plants. To our knowledge, this is the first report of P. hedraiandra in Virginia. Considering neither host plant has been grown or bought for resale by this nursery, this study indicates that P. hedraiandra may have a wider host range than is currently known. This possibility and the importance of water dispersal for P. hedraiandra in disease epidemiology warrant further investigation. References: (1) P. Kong et al. Fungal Genet. Biol. 39:238, 2003. (2) W. A. Man in't Veld et al. Eur. J. Plant Pathol. 117:25, 2007. (3) B. W. Schwingle et al. Plant Dis. 90:109, 2006.

Guidance for Use and dosing of Selinexor in Multiple Myeloma in 2021: Consensus From International Myeloma Foundation Expert Roundtable.

Selinexor is a first in class selective inhibitor of nuclear export (SINE), blocks exportin 1 (XPO1), a protein transporter, that among other actions, shuttles cargo proteins such as tumor suppressor proteins (TSPs), the glucocorticoid receptor (GR), and oncoprotein messenger RNAs (mRNAs) across the nuclear membrane to cytoplasm. By blocking XPO1, selinexor facilitates nuclear preservation and activation of TSPs, and prevents mRNA translation of the oncoproteins leading to induction of apoptosis. The therapeutic value of selinexor in combination with dexamethasone has been successfully demonstrated in treating relapsed and/or refractory myeloma (RRMM), leading to the Food and Drug Administration (FDA) approval of selinexor in combination with dexamethasone in 2019 for the treatment of adult patients with RRMM who received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody (mAb) - a pentarefractory myeloma. More recently, selinexor in combination with bortezomib and dexamethasone was approved by the FDA in December 2020, based on the BOSTON study among RRMM patients who had received at least one prior line of therapy. With more available safety and efficacy data supporting the increased interval between dosing of selinexor (and lesser cumulative weekly dosing) and schedule, contrary to the originally approved dose of 160 mg per week, the supportive care guidelines needed to be revisited. The current manuscript summarizes the supportive care solutions with weekly dosing of selinexor and identifies the ideal potential patient for selinexor treatment.

Genome sequence of the verrucomicrobium Opitutus terrae PB90-1, an abundant inhabitant of rice paddy soil ecosystems.

Bacteria of the deeply branching phylum Verrucomicrobia are rarely cultured yet commonly detected in metagenomic libraries from aquatic, terrestrial, and intestinal environments. We have sequenced the genome of Opitutus terrae PB90-1, a fermentative anaerobe within this phylum, isolated from rice paddy soil and capable of propionate production from plant-derived polysaccharides.

Genome sequence of Victivallis vadensis ATCC BAA-548, an anaerobic bacterium from the phylum Lentisphaerae, isolated from the human gastrointestinal tract.

Victivallis vadensis ATCC BAA-548 represents the first cultured representative from the novel phylum Lentisphaerae, a deep-branching bacterial lineage. Few cultured bacteria from this phylum are known, and V. vadensis therefore represents an important organism for evolutionary studies. V. vadensis is a strictly anaerobic sugar-fermenting isolate from the human gastrointestinal tract.