Citations

Transplantation of autologous mesenchymal stem cells (MSCs) may be a viable option for treatment of several diseases. MSCs efficacy depends on adequate function of their mitochondria, which might be impaired in a noxious milieu. We hypothesized that obesity compromises MSCs mitochondrial structure and function, possibly via micro‐RNA (miRNA)‐based mechanisms. MSCs were collected from swine abdominal adipose tissue after 16 weeks of Lean or Obese diet (n = 7 each). Mitochondrial structure was assessed by electron microscopy and function by membrane potential and cytochrome‐c oxidase (COX)‐IV activity. Oxidative stress was assessed by Mito‐SOX and dihydroethidium staining. Next‐generation sequencing (RNA‐seq) was performed to identify miRNAs expression in MSCs, and predicted mitochondrial target genes were then identified (MitoCarta). Compared to Lean‐MSCs, mitochondria from Obese‐MSCs were smaller and showed cristae remodeling and loss. Mitochondrial membrane potential and COX‐IV activity decreased in Obese‐MSCs, associated with increased mitochondrial oxidative stress. RNA‐seq generated reads for 413 miRNAs, of which 5 miRNAs were upregulated in Obese‐MSCs (fold change >2, p < 0.05) and found to target 43 specific mitochondrial genes. Obesity impairs MSC mitochondrial structure and function, possibly mediated partly through miRNA‐induced mitochondrial gene regulation, leading to increased oxidative stress. Importantly, these alterations may limit the therapeutic use of autologous MSCs in subjects with obesity.

Members of the Society of Hospital Medicine were surveyed about geographic cohorting (GCh); 369 responses were analyzed, two thirds of which were from GCh participants. Improved collaboration with the bedside nurse, increased nonclinical interactions, decreased paging interruptions, and improved efficiency were perceived by >50%. Narrowed clinical expertise, increased fragmentation, increased face-to-face interruptions, and an adverse impact on camaraderie within the hospitalist group were reported by 25% to 50%. Academic practices were associated with positive perceptions while higher patient loads were associated with negative perceptions. Comments on GCh benefits invoked improvements in (1) interprofessional collaboration, (2) efficiency, (3) patient-centeredness, (4) nursing satisfaction, and (5) GCh mediated facilitation of other interventions. GCh downsides included (1) professional and personal dissatisfaction, (2) concerns about providing suboptimal care, and (3) implementation barriers. GCh is receiving attention. Although it facilitates important benefits, it is perceived to mediate unintended consequences, which should be addressed in redesign efforts.

Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a rare T-cell lymphoma that arises around breast implants. Most patients manifest with periprosthetic effusion, whereas a subset of patients develops a tumor mass or lymph node involvement (LNI). The aim of this study is to describe the pathologic features of lymph nodes from patients with BI-ALCL and assess the prognostic impact of LNI. Clinical findings and histopathologic features of lymph nodes were assessed in 70 patients with BI-ALCL. LNI was defined by the histologic demonstration of ALCL in lymph nodes. Fourteen (20%) patients with BI-ALCL had LNI, all lymph nodes involved were regional, the most frequent were axillary (93%). The pattern of involvement was sinusoidal in 13 (92.9%) cases, often associated with perifollicular, interfollicular, and diffuse patterns. Two cases had Hodgkin-like patterns. The 5-year overall survival was 75% for patients with LNI and 97.9% for patients without LNI at presentation (P=0.003). Six of 49 (12.2%) of patients with tumor confined by the capsule had LNI, compared with LNI in 8/21 (38%) patients with tumor beyond the capsule. Most patients with LNI achieved complete remission after various therapeutic approaches. Two of 14 (14.3%) patients with LNI died of disease compared with 0/56 (0%) patients without LNI. Twenty percent of patients with BI-ALCL had LNI by lymphoma, most often in a sinusoidal pattern. We conclude that BI-ALCL beyond capsule is associated with a higher risk of LNI. Involvement of lymph nodes was associated with decreased overall survival. Misdiagnosis as Hodgkin lymphoma is a pitfall.

PurposeDynamic manganese‐enhanced MRI (MEMRI) allows assessment of tissue viability by tracing manganese uptake. We aimed to develop a rapid T1 mapping method for dynamic MEMRI to facilitate assessments of murine kidney viability.MethodsA multi‐slice saturation recovery fast spin echo (MSRFSE) was developed, validated, and subsequently applied in dynamic MEMRI at 16.4T on ischemic mouse kidneys after 4 weeks of unilateral renal artery stenosis (RAS). Baseline T1 values and post‐contrast R1 (1/T1) changes were measured in cortex (CO), outer (OSOM), inner (ISOM) strips of outer medulla, and inner medulla (IM).ResultsValidation studies showed strong agreement between MSRFSE and an established saturation recovery Look‐Locker method. Baseline T1 (s) increased in the stenotic kidney CO (2.10 [1.95–2.56] vs. 1.88 [1.81–2.00], P = 0.0317) and OSOM (2.17 [2.05–2.33] vs. 1.96 [1.87–2.00], P = 0.0075) but remained unchanged in ISOM and IM. This method allowed a temporal resolution of 1.43 min in dynamic MEMRI. Mn2+ uptake and retention decreased in stenotic kidneys, particularly in the OSOM (ΔR1: 0.48 [0.38–0.56] vs. 0.64 [0.61–0.69] s−1, P < 0.0001).ConclusionDynamic MEMRI by MSRFSE detected decreased cellular viability and discerned the regional responses to RAS. This technique may provide a valuable tool for noninvasive evaluation of renal viability. Magn Reson Med 80:190–199, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Background We previously presented that women with chronic rhinosinusitis (CRS) who elected endoscopic sinus surgery (ESS) have a higher symptom burden than men. Causes of these gender-based differences warranted further study. Objectives To study gender differences in another cohort of adult patients with CRS who underwent ESS and to compare key histopathologic and serologic features Methods Patients with CRS who underwent ESS (from 2011 to 2014) with structured histopathology reports on surgical samples were studied. The 13-item structured histopathology report detailed key metrics of inflammation and the presence of fungal elements. Clinical, 22-item Sino-Nasal Outcome Test (SNOT-22) score, Lund-Mackay computed tomography (CT) score, serologic (immunoglobulin E [IgE] level, absolute eosinophil count) and histopathologic data were compared between male and female patients by using statistical software. Results We studied 130 eligible subjects (mean age, 54.7 years; 49.2% women). Compared with the men, the women had significantly higher preoperative SNOT-22 scores (women, 48.7; men 38.0 [p = 0.004]) but similar CT scores. Serum IgE levels were significantly higher among women versus men (peak, 433.3 versus 190.8 kU/L [p = 0.03]; closest to surgery, 435.0 versus 190.8 kU/L [p = 0.03]). Tissue fungal elements were significantly more prevalent in women versus men (19.0 versus 5.2%; p = 0.02). Up to this point, the analysis was agnostic of clinical details of the subjects. Further analysis was conducted regarding clinical features. Allergic fungal sinusitis (AFS) was found significantly more commonly in the female versus male patients (21.9 versus 9.1%; p = 0.04). Women versus men had a higher prevalence of migraine (19.4 versus 4.6%; p = 0.01) or any primary headache disorders (23.0 versus 6.2%; p = 0.007). Conclusion Women who underwent ESS for CRS had higher SNOT-22 symptom burden. Worsened symptomatology may be secondary to a higher prevalence of primary headache disorders in women. However, surgeons should also be aware that female patients with CRS who seek ESS may have a higher prevalence of severe disease endotypes (more tissue fungal elements, elevated serum IgE levels) and phenotypes.

Background and Purpose— White matter (WM) ischemic injury, a major neuropathological feature of cerebral small vessel diseases, is an important cause of vascular cognitive impairment in later life. The pathogenesis of demyelination after WM ischemic damage are often accompanied by microglial activation. Fingolimod (FTY720) was approved for the treatment of multiple sclerosis for its immunosuppression property. In this study, we evaluated the neuroprotective potential of FTY720 in a WM ischemia model. Methods— Chronic WM ischemic injury model was induced by bilateral carotid artery stenosis. Cognitive function, WM integrity, microglial activation, and potential pathway involved in microglial polarization were assessed after bilateral carotid artery stenosis. Results— Disruption of WM integrity was characterized by demyelination in the corpus callosum and disorganization of Ranvier nodes using Luxol fast blue staining, immunofluorescence staining, and electron microscopy. In addition, radial maze test demonstrated that working memory performance was decreased at 1-month post–bilateral carotid artery stenosis–induced injury. Interestingly, FTY720 could reduce cognitive decline and ameliorate the disruption of WM integrity. Mechanistically, cerebral hypoperfusion induced microglial activation, production of associated proinflammatory cytokines, and priming of microglial polarization toward the M1 phenotype, whereas FTY720 attenuated microglia-mediated neuroinflammation after WM ischemia and promoted oligodendrocytogenesis by shifting microglia toward M2 polarization. FTY720’s effect on microglial M2 polarization was largely suppressed by selective signal transducer and activator of transcription 3 (STAT3) blockade in vitro, revealing that FTY720-enabled shift of microglia from M1 to M2 polarization state was possibly mediated by STAT3 signaling. Conclusions— Our study suggested that FTY720 might be a potential therapeutic drug targeting brain inflammation by skewing microglia toward M2 polarization after chronic cerebral hypoperfusion.

SummaryDue to the introduction of newer, more efficacious treatment options, there is a pressing need for policy makers and public health officials to develop or adapt national hepatitis C virus (HCV) control strategies to the changing epidemiological landscape. To do so, detailed, country‐specific data are needed to characterize the burden of chronic HCV infection. In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Hong Kong to 2.4% in Taiwan, while the largest viraemic populations were in Nigeria (2 597 000 cases) and Taiwan (569 000 cases). Diagnosis, treatment and liver transplant rates varied widely across the countries included in this analysis, as did the availability of reliable data. Addressing data gaps will be critical for the development of future strategies to manage and minimize the disease burden of hepatitis C.

SummaryFactors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV‐related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high‐treatment rate will contribute to a reduction in total cases and HCV‐related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV‐related morbidity and mortality.

SummaryThe hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets—“WHO Targets” (65% reduction in HCV‐related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.