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Polycythemia vera (PV) is characterized by erythropoiesis and JAK2- activating mutations, with increased risks of morbidity and mortality. Most patients with PV are iron deficient, and treatment often includes hematocrit control with phlebotomy, which may exacerbate iron deficiency-associated complications. The phase 3 RESPONSE trial evaluated the JAK1/JAK2 inhibitor ruxolitinib (n = 110) versus best available therapy (BAT; n = 112) in patients with PV who were hydroxyurea-resistant/intolerant. Ruxolitinib was superior to BAT for hematocrit control, reduction in splenomegaly, and blood count normalization. This exploratory analysis, the first to evaluate iron status in a prospective study of patients with PV, investigated ruxolitinib effects on 7 serum iron markers and iron deficiency-related patient-reported outcomes (PRO). Among patients with evidence of baseline iron deficiency, ruxolitinib was associated with normalization of iron marker levels, compared with lesser improvement with BAT. Iron levels remained stable in ruxolitinib patients with normal iron levels at baseline. Regardless of baseline iron status, treatment with ruxolitinib was associated with improvements in concentration problems, cognitive function, dizziness, fatigue, headaches, and inactivity, although improvements were generally greater among patients with baseline iron deficiency. The improvements in iron deficiency markers and PROs observed with ruxolitinib are suggestive of clinical benefits that warrant further exploration. [ABSTRACT FROM AUTHOR]

Background: This analysis of the myeloproliferative neoplasm (MPN) Landmark survey evaluated gaps between patient perceptions of their disease management and physician self-reported practices.Methods: The survey included 813 patient respondents who had MPNs (myelofibrosis [MF], polycythemia vera [PV], or essential thrombocythemia [ET]) and 457 hematologist/oncologist respondents who treated patients with these conditions.Results: Greater proportions of physician respondents reported using prognostic risk classifications (MF, 83%; PV, 59%; ET, 77%) compared with patient recollections (MF, 54%; PV, 17%; ET, 31%). Most physician respondents reported that their typical symptom assessments included asking patients about the most important symptoms or a full list of symptoms, whereas many patient respondents reported less specific assessments (eg, they were asked how they were feeling). Many patient respondents did not recognize common symptoms as MPN-related. For example, approximately one-half or more did not believe difficulty sleeping resulted from their MPN (MF, 49%; PV, 64%; ET, 76%). Physician respondents underestimated the proportion of patients who had symptomatic PV or ET at diagnosis compared with patient respondents. There was discordance regarding treatment goals: among patient respondents with MF or PV, "slow/delay progression of condition" was the most important treatment goal, whereas physician respondents reported "symptom improvement" and "prevention of vascular/thrombotic events," respectively. Finally, more than one-third of patient respondents were not "very satisfied" with their physician's overall management/communication.Conclusions: The care and satisfaction of patients with MPN may be improved with increased patient education and improved patient-physician communication. Cancer 2017;123:449-458. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. [ABSTRACT FROM AUTHOR]

While rapid demographic changes in Asia are driving the incidence of chronic aging-related diseases, the limited availability of high-quality in vivo data hampers our ability to understand complex multi-factorial contributions, including gut microbial, to healthy aging. Leveraging a well-phenotyped cohort of community-living octogenarians in Singapore, we used deep shotgun-metagenomic sequencing for high-resolution taxonomic and functional characterization of their gut microbiomes (n = 234). Joint species-level analysis with other Asian cohorts identified distinct age-associated shifts characterized by reduction in microbial richness, and specific Alistipes and Bacteroides species enrichment (e.g., Alistipes shahii and Bacteroides xylanisolvens). Functional analysis confirmed these changes correspond to metabolic potential expansion in aging towards alternate pathways synthesizing and utilizing amino-acid precursors, vis-à-vis dominant microbial guilds producing butyrate in gut from pyruvate (e.g., Faecalibacterium prausnitzii, Roseburia inulinivorans). Extending these observations to key clinical markers helped identify >10 robust microbial associations to inflammation, cardiometabolic and liver health, including potential probiotic species (e.g., Parabacteroides goldsteinii) and pathobionts (e.g., Klebsiella pneumoniae), highlighting the microbiome's role as biomarkers and potential targets for promoting healthy aging., (© 2024. The Author(s).)

Purpose: This study aimed to describe healthcare resource utilization and costs among individuals with vitiligo who were diagnosed with ≥1 psychosocial comorbidity, using data from US claims databases., Patients and Methods: A retrospective, observational cohort analysis of the IBM MarketScan Commercial and Medicare supplemental claims databases for US individuals with vitiligo aged ≥12 years and a first vitiligo claim between January 1 and December 31, 2018, was undertaken to assess psychosocial burden, including mental and behavioral health comorbidities., Results: Of the 12,427 individuals included in the analysis, nearly 1 in 4 (23.5%) who had vitiligo were also diagnosed with ≥1 psychosocial comorbidity. A greater percentage of these individuals versus those who were not diagnosed with a psychosocial comorbidity had a vitiligo-related prescription claim (50.2% vs 45.4%; P <0.0001), especially for oral corticosteroids (25.4% vs 16.6%; P <0.0001) and low-potency topical corticosteroids (9.0% vs 7.6%; P <0.05). Total vitiligo-related healthcare resource utilization and costs were consistent among individuals with and without psychosocial comorbidity despite significantly ( P <0.05) higher vitiligo-related ER visit utilization and expenditure among those with psychosocial comorbidity. Furthermore, individuals diagnosed with vitiligo and ≥1 psychosocial comorbidity had significantly ( P <0.0001) greater utilization of all-cause mean prescription claims (25.0 vs 12.8), outpatient services (other than physician and ER visits: 19.5 vs 11.3), outpatient physician visits (10.1 vs 6.4), inpatient stays (0.6 vs 0.1), and ER visits (0.4 vs 0.2) and incurred significantly higher mean (SD) direct medical expenditures ($18,804 [$46,621] vs $9833 [$29,094] per patient per year; P <0.0001)., Conclusion: Individuals with vitiligo who were diagnosed with ≥1 psychosocial comorbidity incurred greater total all-cause but not vitiligo-related healthcare resource utilization and expenditures than those without diagnosis of psychosocial comorbidities. Identification of psychosocial comorbidities in individuals with vitiligo may be important for multidisciplinary management of vitiligo to reduce overall burden for individuals with vitiligo., Competing Interests: JHL and ABN are employees and shareholders of Incyte Corporation. SD is an employee of Datawave Solutions. DR has received honoraria as a consultant for AbbVie, Abcuro, Almirall, AltruBio, Arena, Astria, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, CSL Behring, Dermavant Sciences, Dermira, Incyte, Janssen, Kymera, Kyowa Kirin, Lilly, Nektar, Novartis, Pfizer, RAPT, Regeneron Pharmaceuticals, Recludix, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, UCB, Viela Bio, and Zura Bio; has received research support from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Dermira, Galderma, Incyte, Janssen, Lilly, Merck, Nektar, Novartis, Pfizer, RAPT, and Regeneron Pharmaceuticals; and has served as a paid speaker for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Dermavant, Incyte, Janssen, Lilly, Novartis, Pfizer, Regeneron Pharmaceuticals, and Sanofi. The authors report no other conflicts of interest in this work., (© 2024 Lofland et al.)

The hypervirulent lineages of Klebsiella pneumoniae (HvKp) cause invasive infections such as Klebsiella-liver abscess. Invasive infection often occurs after initial colonization of the host gastrointestinal tract by HvKp. Over 80% of HvKp isolates belong to the clonal group 23 sublineage I that has acquired genomic islands (GIs) GIE492 and ICEKp10. Our analysis of 12 361 K. pneumoniae genomes revealed that GIs GIE492 and ICEKp10 are co-associated with the CG23-I and CG10118 HvKp lineages. GIE492 and ICEKp10 enable HvKp to make a functional bacteriocin microcin E492 (mccE492) and the genotoxin colibactin, respectively. We discovered that GIE492 and ICEKp10 play cooperative roles and enhance gastrointestinal colonization by HvKp. Colibactin is the primary driver of this effect, modifying gut microbiome diversity. Our in vitro assays demonstrate that colibactin and mccE492 kill or inhibit a range of Gram-negative Klebsiella species and Escherichia coli strains, including Gram-positive bacteria, sometimes cooperatively. Moreover, mccE492 and colibactin kill human anaerobic gut commensals that are similar to the taxa found altered by colibactin in the mouse intestines. Our findings suggest that GIs GIE492 and ICEKp10 enable HvKp to kill several commensal bacterial taxa during interspecies interactions in the gut. Thus, acquisition of GIE492 and ICEKp10 could enable better carriage in host populations and explain the dominance of the CG23-I HvKp lineage., (© The Author(s) [2024]. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Acute graft-versus-host disease (GVHD) remains a barrier to successful allogeneic hematopoietic cell transplantation (HCT) outcomes. This multicenter, retrospective chart review describes disease progression, treatment patterns, hospitalizations, and clinical outcomes among 475 patients (≥12 years old) who developed grades II-IV acute GVHD after their first HCT (January 2014-June 2016). Median (interquartile range) age at HCT was 55 (44-63) years. From the date of acute GVHD diagnosis, 190 patients (40.0%) experienced progression to more severe disease and/or developed new organ involvement. Among 431 patients with grades II-IV acute GVHD at diagnosis, 73.1% received first-line systemic corticosteroids. During follow-up (median 524 days since acute GVHD diagnosis), 23.4% of patients had an increase in steroid dose and 44.4% were unable to taper below 10 mg/day. Over half of patients (54.9%) required ≥1 hospital readmission within 100 days post-HCT (≥2 readmissions in 22.3%); mean inpatient length of stay upon readmission was 27.5 days. Approximately half of patients (52.8%) died during follow-up; 1-year overall mortality from date of acute GVHD diagnosis and nonrelapse mortality rates were 35.2% and 25.5%, respectively. Overall, patients who developed acute GVHD following HCT had poor clinical outcomes, highlighting the unmet need for early and effective treatment strategies., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Atopic dermatitis (AD) is a common chronic skin condition in children (15-20%) that can significantly impair their quality of life. As a result of its relapsing nature and enrichment of Staphylococcus aureus during flares, clinical management can include eradicating S aureus from the skin of children; however, this does not extend to their healthy caregivers, who are potential reservoirs., Objective: Our aim was to understand skin microbiome sharing and microbial features in children with AD and their healthy adult caregivers., Methods: We utilized whole-metagenome profiling at 4 body sites (volar forearm, antecubital fossae, cheeks, and lesions) in combination with sequencing of S aureus isolates to characterize a cohort of children with AD and their healthy caregivers (n = 30 families) compared to matched pairs from control households (n = 30 families)., Results: Metagenomic analysis revealed distinct microbiome configurations in the nonlesional skin of AD children and their healthy caregivers versus controls, which were sufficient to accurately predict case-control status (area under the receiver operating characteristic curve > 0.8). These differences were accompanied by significant microbiome similarity between children and their caregivers, indicating that microbiome sharing may play a role in recurrent disease flares. Whole-genome comparisons with high-quality S aureus isolate genomes (n = 55) confirmed significant strain sharing between AD children and their caregivers and AD-specific enrichment of strains expressing enterotoxins Q and K/K2., Conclusion: Our results highlight the distinctive skin microbiome features of healthy caregivers for children with AD and support their inclusion in strategies for the treatment of recurrent pediatric AD., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Acute graft-versus-host disease (GVHD) is a significant cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). This analysis of 168 patients (mean age, 54.8 years) from a multicenter, retrospective chart review describes the clinical course, treatment patterns, hospitalizations, and clinical outcomes of patients aged ≥12 years who developed grades II-IV acute GVHD after their first allogeneic HCT (January 1, 2014, to June 30, 2016) and were refractory to or dependent on corticosteroids. Between diagnosis and maximum grade (median, 6.0 days), 53.6% of patients had new organ involvement, particularly lower gastrointestinal tract acute GVHD, or an increase in acute GVHD grade. Eighty-nine patients (53.0%) received additional systemic GVHD therapy (after systemic corticosteroids) within a median of 21.0 days. Hospital readmission(s) was required for 56.5% of patients within 100 days post-HCT (mean inpatient length of readmission stay, 49.5 days); 24.4% had ≥2 readmissions within 100 days post-HCT. From the date of acute GVHD diagnosis, 70.2% of patients died at a median (interquartile range) of 117.5 (49-258) days. In summary, steroid-refractory and steroid-dependent acute GVHD is associated with a rapidly worsening clinical course that leads to high readmission and mortality rates, emphasizing the need for effective and tolerable therapies., (© 2022. The Author(s).)

The human Fc-gamma receptors (FcγRs) link adaptive and innate immunity by binding immunoglobulin G (IgG). All human low-affinity FcγRs are encoded by the FCGR2/3 locus containing functional single nucleotide polymorphisms (SNPs) and gene copy number variants. This locus is notoriously difficult to genotype and high-throughput methods commonly used focus on only a few SNPs. We performed multiplex ligation-dependent probe amplification for all relevant genetic variations at the FCGR2/3 locus in >4,000 individuals to define linkage disequilibrium (LD) and allele frequencies in different populations. Strong LD and extensive ethnic variation in allele frequencies was found across the locus. LD was strongest for the FCGR2C -ORF haplotype (rs759550223+rs76277413), which leads to expression of FcγRIIc. In Europeans, the FCGR2C -ORF haplotype showed strong LD with, among others, rs201218628 ( FCGR2A -Q27W, r 2 = 0.63). LD between these two variants was weaker ( r 2 = 0.17) in Africans, whereas the FCGR2C -ORF haplotype was nearly absent in Asians (minor allele frequency <0.005%). The FCGR2C -ORF haplotype and rs1801274 ( FCGR2A -H131R) were in weak LD ( r 2 = 0.08) in Europeans. We evaluated the importance of ethnic variation and LD in Kawasaki Disease (KD), an acute vasculitis in children with increased incidence in Asians. An association of rs1801274 with KD was previously shown in ethnically diverse genome-wide association studies. Now, we show in 1,028 European KD patients that the FCGR2C -ORF haplotype, although nearly absent in Asians, was more strongly associated with susceptibility to KD than rs1801274 in Europeans. Our data illustrate the importance of interpreting findings of association studies concerning the FCGR2/3 locus with knowledge of LD and ethnic variation.

A simple procedure based on anion exchange was employed for the enantiomeric resolution of the extended metal atom chain (EMAC) [Co 3 (dpa) 4 (MeCN) 2 ] 2+ . Use of the chiral salt (NBu 4 ) 2 [As 2 (tartrate) 2 ], (Λ- 1 or Δ- 1 ), resulted in the selective crystallization of the EMAC enantiomers as [Δ-Co 3 (dpa) 4 (MeCN) 2 ](NBu 4 ) 2 [Λ-As 2 (tartarte) 2 ] 2 , (Δ- 2 ) and [Λ-Co 3 (dpa) 4 (MeCN) 2 ](NBu 4 ) 2 [Δ-As 2 (tartrate) 2 ] 2 (Λ- 2 ), respectively, in the P 42 1 2 space group, whereas a racemic mixture of 1 yielded [Co 3 (dpa) 4 (MeCN) 2 ][As 2 (tartrate) 2 ]·2MeCN ( rac - 3 ), which crystallized in the C 2/ c space group. The local electronic and magnetic structure of the EMAC enantiomers was studied, exploiting a variety of dichroisms in single crystals. A strong linear dichroism at the Co K-edge was observed in the orthoaxial configuration, whereas it vanished in the axial orientation, thus spectroscopically confirming the D 4 crystal symmetry. Compounds Δ- 2 and Λ- 2 are shown to be enantiopure materials as evidenced by mirror-image natural circular dichroism spectra in the UV/vis in solution and in the X-ray range at the Co K-edge in single crystals. The surprising absence of detectable X-ray magnetic circular dichroism or X-ray magnetochiral dichroism signals at the Co K-edge, even at low temperature (3 K) and a high magnetic field (17 T), is ascribed to a strongly delocalized spin density on the tricobalt core.

Background: Limited information is available on patients' perspectives of shared decision-making practices used in inflammatory bowel disease (IBD)., Objective: The aim of this study was to examine patient insights regarding shared decision making among patients with IBD using novel statistical technology to analyze qualitative data., Methods: Two 10-patient focus groups (10 ulcerative colitis patients and 10 Crohn's disease patients) were conducted in Chicago in January 2012 to explore patients' experiences, concerns, and preferences related to shared decision making. Key audio excerpts of focus group insights were embedded within a 25-min online patient survey and used for moment-to-moment affect trace analysis., Results: A total of 355 IBD patients completed the survey (ulcerative colitis 51 %; Crohn's disease 49 %; female 54 %; 18-50 years of age 50 %). The majority of patients (66 %) reported increased satisfaction when they participated in shared decision making. Three unique patient clusters were identified based on their involvement in shared decision making: satisfied, content, and dissatisfied. Satisfied patients (18 %) had a positive physician relationship and a high level of trust with their physician. Content patients (48 %) had a moderate level of trust with their physician. Dissatisfied patients (34 %) had a life greatly affected by IBD, a low level of trust of their physician, a negative relationship with their physician, were skeptical of decisions, and did not rely on their physician for assistance., Conclusion: This study provides valuable insights regarding patients' perceptions of the shared decision-making process in IBD treatment using a novel moment-to-moment hybrid technology approach. Patient perspectives in this study indicate an increased desire for shared decision making in determining an optimal IBD treatment plan.

Background: Global gene expression profiling can provide insight into the underlying pathophysiology of disease processes. Kawasaki disease (KD) is an acute, self-limited vasculitis whose etiology remains unknown. Although the clinical illness shares certain features with other pediatric infectious diseases, the occurrence of coronary artery aneurysms in 25% of untreated patients is unique to KD., Methods: To gain further insight into the molecular mechanisms underlying KD, we investigated the acute and convalescent whole blood transcriptional profiles of 146 KD subjects and compared them with the transcriptional profiles of pediatric patients with confirmed bacterial or viral infection, and with healthy control children. We also investigated the transcript abundance in patients with different intravenous immunoglobulin treatment responses and different coronary artery outcomes., Results: The overwhelming signature for acute KD involved signaling pathways of the innate immune system. Comparison with other acute pediatric infections highlighted the importance of pathways involved in cell motility including paxillin, relaxin, actin, integrins, and matrix metalloproteinases. Most importantly, the IL1β pathway was identified as a potential therapeutic target., Conclusion: Our study revealed the importance of the IL-1 signaling pathway and a prominent signature of innate immunity and cell migration in the acute phase of the illness.

Objective: To determine productivity loss and indirect costs with deep vein thrombosis (DVT) and pulmonary embolism (PE)., Methods: Medical and pharmacy claims with short-term disability (STD) and long-term disability (LTD) claims from 2007 to 2010 were analyzed from the Integrated Benefits Institute's Health and Productivity Benchmarking (IBI-HPB) database (STD and LTD claims) and IMS LifeLink™ data (medical and pharmacy claims), which were indirectly linked using a weighting approach matching from IBI-HPB patients' demographic distribution., Results: A total of 5442 DVT and 6199 PE claims were identified. Employees with DVT lost 57 STD and 440 LTD days per disability incident. The average per claim productivity loss from STD and LTD was $7414 and $58181, respectively. Employees with PE lost 56 STD and 364 LTD days per disability incident. The average per claim productivity loss from STD and LTD was $7605 and $48,751, respectively., Conclusions: Deep vein thrombosis and PE impose substantial economic burdens.

Objective: To evaluate how changes in infliximab dose influence resource utilization and expenditures for patients with rheumatoid arthritis (RA)., Research Design and Methods: A retrospective analysis using claims from January 1, 1999 through March 31, 2005 in the MedStat MarketScan databases for RA patients who had an increase, decrease, or no change in infliximab dose within 1 year of initiating therapy. Eligibility criteria included at least one claim with a diagnosis of RA and no biologic treatment within 6 months before the index infliximab claim, continuous health plan enrollment (commercial or Medicare) for 6 months before and 12 months after the index date, and three consecutive infliximab infusions. The index and final infliximab doses were estimated from claims data., Results: Data were included for 1678 commercially insured patients and 616 Medicare-eligible patients; 45.4% and 39.3%, respectively, had an increase in dose, 24.7% and 43.2%, respectively, had a decrease in dose, and 29.9% and 17.5%, respectively, had no change in dose. Overall, resource utilization was higher in the increase-in-dose groups and lower in the no change-in-dose groups when compared with the decrease-in-dose groups for both cohorts. Medical costs were also highest for the increase-in-dose groups for both cohorts. Pharmacy expenditures for the no-change-in-dose groups were lower than the decrease-in-dose groups in both cohorts., Conclusions: An increase in dose was the most common dose change for the commercial cohort, while a decrease in dose was the most common dose change for the Medicare-eligible cohort. Patients with an increase in dose had the highest utilization and expenditures while those with no change in dose had the lowest levels. The nature of this utilization needs to be examined to better understand how dosing changes may influence medical utilization. Changes in dose were defined by the difference between the first and final doses and may not have captured changes in interim doses.