Patterns of interventions for central venous catheter-associated deep vein thrombosis and outcomes in cancer patients.

PURPOSE: This letter evaluated the impact of different management strategies, specifically the presence or absence of therapeutic anticoagulation, on clinical outcomes for central venous catheter (CVC)-associated deep vein thrombosis (DVT) in cancer patients. METHODS: One-hundred ninety-eight adult cancer patients with a confirmed CVC-associated DVT diagnosis from February 2013 and February 2021 were included. RESULTS: Incidence of symptomatic recurrent venous thromboembolism (VTE) was similar between patients who received therapeutic anticoagulation and those who did not (14% vs 16%, p = 0.807). In addition, therapeutic anticoagulation did not significantly alter the incidence of grade 3 and above bleeding events despite most patients having hematologic malignancies (9% vs 8%, p = 0.826). CONCLUSION AND RELEVANCE: Therapeutic anticoagulation was not associated with a reduction in the incidence of recurrent VTE or increase the incidence of bleeding in adult cancer patients following a CVC-associated DVT diagnosis.

Vacuum-sealed silicon photonic MEMS tunable ring resonator with an independent control over coupling and phase.

Ring resonators are a vital element for filters, optical delay lines, or sensors in silicon photonics. However, reconfigurable ring resonators with low-power consumption are not available in foundries today. We demonstrate an add-drop ring resonator with the independent tuning of round-trip phase and coupling using low-power microelectromechanical (MEMS) actuation. At a wavelength of 1540 nm and for a maximum voltage of 40 V, the phase shifters provide a resonance wavelength tuning of 0.15 nm, while the tunable couplers can tune the optical resonance extinction ratio at the through port from 0 to 30 dB. The optical resonance displays a passive quality factor of 29 000, which can be increased to almost 50 000 with actuation. The MEMS rings are individually vacuum-sealed on wafer scale, enabling reliable and long-term protection from the environment. We cycled the mechanical actuators for more than 4 × 109 cycles at 100 kHz, and did not observe degradation in their response curves. On mechanical resonance, we demonstrate a modulation increase of up to 15 dB, with a voltage bias of 4 V and a peak drive amplitude as low as 20 mV.

Progressive multifocal leukoencephalopathy as the presenting feature in a patient with occult low-count monoclonal B-cell lymphocytosis.

Introduction: Low Count Monoclonal B-Cell Lymphocytosis (LC-MBL) is a relatively poorly understood entity which has been suggested to be very common in asymptomatic adults and possibly related to infectious complications despite not progressing to CLL. Methods: We describe the first case of Progressive Multifocal Leukoencephalopathy (PML) presenting in a 72-year-old man with LC-MBL but no other immunocompromising conditions. Results: A diagnosis of PML was confirmed with classic MRI findings in association with a high CSF John Cunningham polyomavirus (JCV) viral load (4.09' 105 copies/mL). An extensive search for underlying immunocompromising conditions only demonstrated LC-MBL representing approximately 4% of total leukocytes (0.2' 109/L). Discussion: This is the first report of PML in association with LC-MBL. Careful review of peripheral blood flow cytometry results is necessary to identify this disorder. Further study of the epidemiology and infectious complications of LC-MBL are warranted.

Introduction: La lymphocytose monoclonale à cellules B (LMB) est une maladie relativement mal comprise qui serait très courante chez des adultes asymptomatiques et qui pourrait être liée à des complications infectieuses, même si elle n'évolue pas en leucémie lymphocytique chronique. Méthodologies: Nous décrivons le premier cas de leucoencéphalopathie multifocale progressive (LEMP) observé chez un patient (72 ans) atteint de LMB, mais ne présentant pas d'autres pathologies induisant une immunodéficience. Résultats: Des résultats d'IRM classiques et une forte charge du virus JC (John Cunningham) dans le liquide céphalorachidien (4,09 × 105 copies/mL) ont confirmé un diagnostic de LEMP. De nombreux tests visant à révéler une immunodéficience sous-jacente ont seulement montré que les cellules B monoclonales représentaient environ 4% des leucocytes totaux (0,2 × 109/L). Discussion: Il s'agit du premier cas observé de LEMP en association avec une LMB. Il faut analyser soigneusement les résultats d'une cytométrie en flux du sang périphérique pour diagnostiquer ce trouble. Il convient de continuer d'étudier l'épidémiologie et les complications infectieuses de la LMB.

Investigation of the chemical composition of antibacterial Psidium guajava extract and partitions against foodborne pathogens.

P. guajava was partitioned into aqueous and ethyl acetate fractions and studied for its antibacterial chemical constituents. The minimum inhibitory concentrations of the aqueous and ethyl acetate partitions against Escherichia coli, Salmonella Typhimurium, and Staphylococcus aureus were found to be 0.75, 0.75, 0.15, 0.5, 0.5, and 0.125%, respectively. Using LC-MS-based chemical fingerprinting, auto MS/MS fragmentation and bioactive molecular networking, 18 compounds of interest were detected. The top 10 bioactive compounds and eight additional non-bioactive compounds known to be found in P. guajava are highlighted. We report five compounds to be identified in P. guajava for the first time. Studies have indicated P. guajava to be a plant source of antibacterial compounds that could be useful in the food industry to prevent foodborne illnesses outbreaks, reduce food spoilage, and satisfy consumer demands for less synthetic chemical usage in the food industry.

Multivariate adaptive shrinkage improves cross-population transcriptome prediction for transcriptome-wide association studies in underrepresented populations.

Transcriptome prediction models built with data from European-descent individuals are less accurate when applied to different populations because of differences in linkage disequilibrium patterns and allele frequencies. We hypothesized methods that leverage shared regulatory effects across different conditions, in this case, across different populations may improve cross-population transcriptome prediction. To test this hypothesis, we made transcriptome prediction models for use in transcriptome-wide association studies (TWAS) using different methods (Elastic Net, Joint-Tissue Imputation (JTI), Matrix eQTL, Multivariate Adaptive Shrinkage in R (MASHR), and Transcriptome-Integrated Genetic Association Resource (TIGAR)) and tested their out-of-sample transcriptome prediction accuracy in population-matched and cross-population scenarios. Additionally, to evaluate model applicability in TWAS, we integrated publicly available multi-ethnic genome-wide association study (GWAS) summary statistics from the Population Architecture using Genomics and Epidemiology Study (PAGE) and Pan-UK Biobank with our developed transcriptome prediction models. In regard to transcriptome prediction accuracy, MASHR models performed better or the same as other methods in both population-matched and cross-population transcriptome predictions. Furthermore, in multi-ethnic TWAS, MASHR models yielded more discoveries that replicate in both PAGE and PanUKBB across all methods analyzed, including loci previously mapped in GWAS and new loci previously not found in GWAS. Overall, our study demonstrates the importance of using methods that benefit from different populations' effect size estimates in order to improve TWAS for multi-ethnic or underrepresented populations.

Multivariate adaptive shrinkage improves cross-population transcriptome prediction and association studies in underrepresented populations.

Transcriptome prediction models built with data from European-descent individuals are less accurate when applied to different populations because of differences in linkage disequilibrium patterns and allele frequencies. We hypothesized that methods that leverage shared regulatory effects across different conditions, in this case, across different populations, may improve cross-population transcriptome prediction. To test this hypothesis, we made transcriptome prediction models for use in transcriptome-wide association studies (TWASs) using different methods (elastic net, joint-tissue imputation [JTI], matrix expression quantitative trait loci [Matrix eQTL], multivariate adaptive shrinkage in R [MASHR], and transcriptome-integrated genetic association resource [TIGAR]) and tested their out-of-sample transcriptome prediction accuracy in population-matched and cross-population scenarios. Additionally, to evaluate model applicability in TWASs, we integrated publicly available multiethnic genome-wide association study (GWAS) summary statistics from the Population Architecture using Genomics and Epidemiology (PAGE) study and Pan-ancestry genetic analysis of the UK Biobank (PanUKBB) with our developed transcriptome prediction models. In regard to transcriptome prediction accuracy, MASHR models performed better or the same as other methods in both population-matched and cross-population transcriptome predictions. Furthermore, in multiethnic TWASs, MASHR models yielded more discoveries that replicate in both PAGE and PanUKBB across all methods analyzed, including loci previously mapped in GWASs and loci previously not found in GWASs. Overall, our study demonstrates the importance of using methods that benefit from different populations' effect size estimates in order to improve TWASs for multiethnic or underrepresented populations.

PROMISE: a real-world clinical-genomic database to address knowledge gaps in prostate cancer.

PURPOSE: Prostate cancer is a heterogeneous disease with variable clinical outcomes. Despite numerous recent approvals of novel therapies, castration-resistant prostate cancer remains lethal. A "real-world" clinical-genomic database is urgently needed to enhance our characterization of advanced prostate cancer and further enable precision oncology. METHODS: The Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) is a consortium whose aims are to establish a repository of de-identified clinical and genomic patient data that are linked to patient outcomes. The consortium structure includes a (1) bio-informatics committee to standardize genomic data and provide quality control, (2) biostatistics committee to independently perform statistical analyses, (3) executive committee to review and select proposals of relevant questions for the consortium to address, (4) diversity/inclusion committee to address important clinical questions pertaining to racial disparities, and (5) patient advocacy committee to understand patient perspectives to improve patients' quality of care. RESULTS: The PROMISE consortium was formed by 16 academic institutions in early 2020 and a secure RedCap database was created. The first patient record was entered into the database in April 2020 and over 1000 records have been entered as of early 2021. Data entry is proceeding as planned with the goal to have over 2500 patient records by the end of 2021. CONCLUSIONS: The PROMISE consortium provides a powerful clinical-genomic platform to interrogate and address data gaps that have arisen with increased genomic testing in the clinical management of prostate cancer. The dataset incorporates data from patient populations that are often underrepresented in clinical trials, generates new hypotheses to direct further research, and addresses important clinical questions that are otherwise difficult to investigate in prospective studies.

Melanoma With an Unknown Primary in an Asymptomatic Elderly Male With Unilateral Lymphadenopathy.

Melanoma with an unknown primary (MUP) is an uncommon metastatic melanoma without an obvious primary site. MUP has a higher prevalence in men in their fifth decade of life. The pathogenesis of MUP is still unknown but several hypotheses have been proposed including the predominant regression theory, occult cutaneous, or visceral location, or by the presence of ectopic melanocytes. Proper physical examination, imaging, and histopathological review are needed to diagnose MUP. Patients with MUP must be aggressively treated and monitored for recurrence. We present a case of MUP occurring in an asymptomatic 61-year-old male with axillary lymphadenopathy. We hope to raise awareness that melanoma of unknown primary can present in lymph nodes without external structural changes.

Efficacy and safety of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in Asian participants with human immunodeficiency virus 1 infection: A sub-analysis of phase 3 clinical trials.

Background: The efficacy and safety of a single tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) was analyzed in Phase 3 clinical trials in antiretroviral therapy (ART)-naive and ART-experienced Asian participants infected with human immunodeficiency virus (HIV)-1 through 96 or 144 weeks.Objective: In Asian population requiring treatment, it is imperative to have data specific to this group, particularly as there is a general concern that Asians with lower body weight have increased risk of tenofovir disoproxil fumarate (TDF)-related renal dysfunction.Methods: Studies -104 and 111 were randomized, double-blind, placebo-controlled, 144-week studies conducted in ART-naive participants, comparing E/C/F/TAF versus E/C/F/TDF. Study 109 was a randomized, open-label, 96-week study conducted in virologically suppressed, ART-experienced participants, who switched to E/C/F/TAF from ritonavir/cobicistat-boosted atazanavir ATV+(RTV or COBI) + F/TDF regimens, from non-nucleoside reverse transcriptase inhibitors (NNRTI) + F/TDF regimens, or from E/C/F/TDF. Study 112 was a single arm, open-label, 144-week study conducted in HIV suppressed, ART-experienced participants with mild-moderate renal impairment, who switched to E/C/F/TAF.Results: Asian participants in these studies had sustained efficacy safety and tolerability. In Study 104/111, Asian participants achieved 93% virologic suppression on TAF vs 88% on TDF at week 144. At baseline, there were numerically more Asians with median CD4 counts < 200 cells/uL and VL > 100,000 c/mL. In Study 109, 95% of Asians on TAF vs 86% on TDF maintained virologic suppression at week 96. Lastly, in Study 112, 91% maintained virologic suppression at week 144. There were no discontinuations due to renal AE, no cases of PRT or Fanconi syndrome in any of the studies.

Cryptococcal meningitis in a daily cannabis smoker without evidence of immunodeficiency.

Cryptococcal meningitis is a life-threatening condition most commonly observed in immunocompromised individuals. We describe a daily cannabis smoker without evidence of immunodeficiency presenting with confirmed Cryptococcus neoformans meningitis. An investigation of cannabis samples from the patient's preferred dispensary demonstrated contamination with several varieties of Cryptococcus, including C. neoformans, and other opportunistic fungi. These findings raise concern regarding the safety of dispensary-grade cannabis, even in immunocompetent users.

Endocuff assisted colonoscopy significantly increases sessile serrated adenoma detection in veterans.

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer related deaths in the United States. Colonoscopy is the gold standard for the detection of CRC. There are many colonoscopy quality measures and among these the adenoma detection rate (ADR) has demonstrated a significant impact in reducing mortality from CRC. The primary aim of our study was to compare ADR and distribution of polyp type in patients undergoing Endocuff-assisted colonoscopy (EAC) versus standard colonoscopy (SC) in a VA system. METHODS: Retrospective data was collected from 496 patients who underwent routine screening, surveillance and diagnostic colonoscopies either via SC from January 6, 2014 through March 12, 2014 or EAC from September 24, 2014 through February 19, 2015. A total of 54 patients were excluded based on a personal history of CRC and prior resection, incomplete colonoscopy due to poor bowel preparation, and removal or loss of Endocuff (EC). Primary outcomes measured and compared were ADR and types of polyps found. RESULTS: The overall ADR in the EAC group was higher at 59.91% versus 50.66% for SC, accounting for a 9% increase (P=0.0508). EAC was able to detect a total of 59 sessile serrated adenoma/polyps (SSA/Ps) compared to SC only detecting 8 (P≤0.0001). There was a significant increase in the SSA/P detection rate with EAC at 15% versus 3% in the SC group (P≤0.0001). CONCLUSIONS: EAC significantly increases the detection of SSA/P and has shown a trend in improving ADR in our veteran population.

Perioperative stroke after cerebral aneurysm clipping: Risk factors and postoperative impact.

Stroke is a devastating complication after intracranial aneurysm clipping. Understanding the risk factors that prognosticate perioperative stroke may help to identify patients that would benefit from neuroprotective therapy. This study assesses patient-specific independent predictors of perioperative stroke in relation to surgical aneurysm clipping. Additionally, this study evaluates the postoperative complications of stroke. We performed a retrospective chart review of 437 patients with ruptured and unruptured intracranial aneurysms, which underwent surgical clipping from 2006 to 2013. Multivariate logistical regression was utilized to assess the effect of age, race, gender, subarachnoid hemorrhage, Hunt and Hess (H/H) grade, aneurysm location, and intraoperative somatosensory evoked potentials (SSEPs) changes on the frequency of perioperative stroke. Thirty-five (8.0%) patients developed a stroke within 24h postoperatively. Patients with significant intraoperative SSEP changes were 7.33 (95% confidence interval [CI]: 3.51-15.31) times more likely to develop perioperative strokes. In patients who presented with H/H grade 5, the odds ratio for developing perioperative stroke was 9.21 (95% CI: 1.28-66.13) respectively. In the absence of aneurysm rupture, patients presenting with new-onset stroke were more likely to suffer postoperative complications, stay in the intensive care unit longer, and be discharged to in-patient rehabilitation compared to patients without new-onset stroke. This study suggests that severity of subarachnoid hemorrhage based on the patient's clinical condition increases the risk of perioperative stroke in patients with surgical aneurysm clipping. SSEP changes and high-grade H/H scores can serve as independent predictors of perioperative stroke, with the latter having the greatest predictive value.