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Left ventricular (LV) mid-wall fibrosis (MWF), which occurs in about a quarter of patients with non-ischemic cardiomyopathy (NICM), is associated with high risk of pump failure. The mid LV wall is the site of circumferential myocardial fibers. We sought to determine the effect of MWF on LV myocardial mechanics. Patients with NICM (n = 116; age: 62.8 ± 13.2 years; 67 % male) underwent late gadolinium enhancement cardiovascular magnetic resonance (CMR) and were categorized according to the presence (+) or absence (−) of MWF. Feature tracking (FT) CMR was used to assess myocardial deformation. Despite a similar LVEF (24.3 vs 27.5 %, p = 0.20), patients with MWF (32 [24 %]) had lower global circumferential strain (Ɛcc: −6.6 % vs −9.4 %, P = 0.004), but similar longitudinal (Ɛll: −7.6 % vs. −9.4 %, p = 0.053) and radial (Ɛrr: 14.6 % vs. 17.8 % p = 0.18) strain. Compared with − MWF, + MWF was associated with reduced LV systolic, circumferential strain rate (−0.38 ± 0.1 vs −0.56 ± 0.3 s−1, p = 0.005) and peak LV twist (4.65 vs. 6.31°, p = 0.004), as well as rigid LV body rotation (64 % vs 28 %, P <0.001). In addition, +MWF was associated with reduced LV diastolic strain rates (DSRcc: 0.34 vs. 0.46 s−1; DSRll: 0.38 vs. 0.50s−1; DSRrr: −0.55 vs. −0.75 s−1; all p <0.05). MWF is associated with reduced LV global circumferential strain, strain rate and torsion. In addition, MWF is associated with rigid LV body rotation and reduced diastolic strain rates. These systolic and diastolic disturbances may be related to the increased risk of pump failure observed in patients with NICM and MWF.

Background and Objectives: Local and systemic inflammation is common after surgery and is associated with morbidity and mortality. Inflammatory cytokines have been implicated in cancer metastasis following cancer surgery. The present study aimed to analyze inflammatory cytokines levels after surgery under combined epidural/general anesthesia (EA + GA) vs. general anesthesia (GA). Methods: We systematically searched PubMed, Central, EMBASE, CINAHL, Google Scholar, and Web of Science citation indexes for clinical studies (cancer and non-cancer surgery) comparing the two techniques. We carried out a meta-analysis to evaluate the postoperative plasma levels of cytokines, C-reactive protein (CRP), and cortisol levels. Results: The literature search was last updated on 2 January 2025. We identified a total of 21 studies which compared postoperative inflammatory mediators with EA plus GA compared to GA alone. EA plus GA was associated with significantly lower serum levels of IL-6, TNF-α, CRP, as well as cortisol and other pro-inflammatory cytokines. In cancer surgery, EA plus GA was also associated with lower postoperative cytokines. Conclusions: Our meta-analysis indicates that EA plus GA is associated with diminished postoperative inflammatory response. This offers an alternative explanation for the benefit of epidural analgesia on postoperative outcomes. Considering the link between postoperative inflammation and recurrence after cancer surgery, this is an area that warrants further research.

OBJECTIVE: Hospital hyperglycemia, in individuals with and without diabetes, has been identified as a marker of poor clinical outcome in cardiac surgery patients. However, the impact of perioperative hyperglycemia on clinical outcome in general and noncardiac surgery patients is not known. RESEARCH DESIGN AND METHODS: This was an observational study with the aim of determining the relationship between pre- and postsurgery blood glucose levels and hospital length of stay (LOS), complications, and mortality in 3,184 noncardiac surgery patients consecutively admitted to Emory University Hospital (Atlanta, GA) between 1 January 2007 and 30 June 2007. RESULTS: The overall 30-day mortality was 2.3%, with nonsurvivors having significantly higher blood glucose levels before and after surgery (both P < 0.01) than survivors. Perioperative hyperglycemia was associated with increased hospital and intensive care unit LOS (P < 0.001) as well as higher numbers of postoperative cases of pneumonia (P < 0.001), systemic blood infection (P < 0.001), urinary tract infection (P < 0.001), acute renal failure (P = 0.005), and acute myocardial infarction (P = 0.005). In multivariate analysis (adjusted for age, sex, race, and surgery severity), the risk of death increased in proportion to perioperative glucose levels; however, this association was significant only for patients without a history of diabetes (P = 0.008) compared with patients with known diabetes (P = 0.748). CONCLUSIONS: Perioperative hyperglycemia is associated with increased LOS, hospital complications, and mortality after noncardiac general surgery. Randomized controlled trials are needed to determine whether perioperative diabetes management improves clinical outcome in noncardiac surgery patients.

Coronary artery calcium score (CACS) is a strong predictor of adverse cardiovascular events in the general population. Recent data confirm the prognostic utility of single-photon emission computed tomographic (SPECT) imaging in end-stage renal disease, but whether performing CACS as part of hybrid imaging improves risk prediction in this population is unclear. Consecutive patients (n = 284) were identified after referral to a university hospital for cardiovascular risk stratification in assessment for renal transplantation. Participants underwent technetium-99m SPECT imaging after exercise or standard adenosine stress in those unable to achieve 85% maximal heart rate; multislice CACS was also performed (Siemens Symbia T16, Siemens, Erlangen, Germany). Subjects with known coronary artery disease (n = 88) and those who underwent early revascularization (n = 2) were excluded. The primary outcome was a composite of death or first myocardial infarction. An abnormal SPECT perfusion result was seen in 22% (43 of 194) of subjects, whereas 45% (87 of 194) had at least moderate CACS (>100 U). The frequency of abnormal perfusion (summed stress score ≥4) increased with increasing CACS severity (p = 0.049). There were a total of 15 events (8 deaths, and 7 myocardial infarctions) after a median duration of 18 months (maximum follow-up 3.4 years). Univariate analysis showed diabetes mellitus (Hazard ratio [HR] 3.30, 95% CI 1.14 to 9.54; p = 0.028), abnormal perfusion on SPECT (HR 5.32, 95% CI 1.84 to 15.35; p = 0.002), and moderate-to-severe CACS (HR 3.55, 95% CI 1.11 to 11.35; p = 0.032) were all associated with the primary outcome. In a multivariate model, abnormal perfusion on SPECT (HR 4.18, 95% CI 1.43 to 12.27; p = 0.009), but not moderate-to-severe CACS (HR 2.50, 95% CI 0.76 to 8.20; p = 0.130), independently predicted all-cause death or myocardial infarction. The prognostic value of CACS was not incremental to clinical and SPECT perfusion data (global chi-square change = 2.52, p = 0.112). In conclusion, a perfusion defect on SPECT is an independent predictor of adverse outcome in potential renal transplant candidates regardless of the CACS. The use of CACS as an adjunct to SPECT perfusion data does not provide incremental prognostic utility for the prediction of mortality and nonfatal myocardial infarction in end-stage renal disease.

NSG-SGM3 humanized mouse models are well-suited for studying human immune physiology but are technically challenging and expensive. We previously characterized a simplified NSG-SGM3 mouse, engrafted with human donor CD34 + hematopoietic stem cells without receiving prior bone marrow ablation or human secondary lymphoid tissue implantation, that still retains human mast cell- and basophil-dependent passive anaphylaxis responses. Its capacities for human antibody production and human B cell maturation, however, remain unknown. Here, we show that NSG-SGM3 mice engrafted without prior marrow ablation spontaneously produce all human antibodies, including IgE, without deliberate sensitization. These human IgE antibodies are polyclonal with unexpected specificities to diverse allergens, such as millet, egg, and wasp venom, that are otherwise absent from the mouse diet or housing environments. Furthermore, human CD138 + CD27 + plasma cell and CD20 + CD27 + memory B cell populations can be expanded from naïve engrafted NSG-SGM3 splenocytes in response to human CD40L and IL-4 cytokine stimulation ex vivo . Engrafted NSG-SGM3 mice, but not non-engrafted controls, also exhibit dose-dependent passive systemic anaphylaxis responses when challenged with goat anti-human IgE. In contrast, no anaphylaxis responses were observed in humanized NSG-SGM3 mice challenged with select food allergens. Together, our results demonstrate that engrafted NSG-SGM3 mice without prior ablation spontaneously produce abundant functional human antibodies, including polyclonal IgE that can facilitate anaphylaxis. These mice also unexpectedly possess the upstream capacity to support human B cell maturation into antibody-producing plasma cells and memory B cells. Our simpler humanized NSG-SGM3 model therefore reveals novel insights into dynamics of human B cell maturation, homing, and differentiation that facilitate the generation of a basal, functional, polyclonal IgE repertoire without deliberate sensitization.

For patients awaiting renal transplantation, there is guideline consensus on the need for ischemia testing but no agreement on the frequency of repeat testing. Moreover, there are no data in this population evaluating changes in ischemia assessed with serial myocardial perfusion imaging. Consecutive patients (n = 649) with end-stage renal disease (ESRD) were referred for cardiovascular risk stratification before renal transplantation between 2007 and 2013. Of these, 151 patients (54 ± 9 years) underwent 2 stress-rest technetium-99m single-photon emission computed tomographic (SPECT) studies with CT attenuation correction in accordance with regional guidelines, which recommend repeat imaging in high-risk subjects who have not undergone renal transplantation within 3 years. An abnormal perfusion result was defined as a summed stress score ≥4. The median interval between imaging was 39 months. At baseline, 28% of patients (42/151) had abnormal SPECT perfusion, half with a fixed defect. Nine subjects (6%) underwent revascularization between SPECT studies after the baseline imaging demonstrated an ischemic perfusion defect size affecting ≥10% of the myocardium. On repeat imaging, 60% (25/42) had abnormal perfusion. In the 72% (109 of 151) with normal baseline SPECT perfusion, 19% (21/109) demonstrated new ischemia at follow-up and 3% (3/109) had an ischemic perfusion defect size ≥10%. The development of new-onset ischemia was associated with systolic hypertension (p = 0.015), serum phosphate (p = 0.043), and Agatston score (p = 0.002), but not diabetes (p = 0.12). In conclusion, there is a high frequency of new-onset ischemia in patients with ESRD awaiting renal transplantation. Further study is needed to define the optimal timing for repeat stress testing.

Patients with alopecia areata (AA) may experience episodic hair loss that follows seasonal patterns. To assess associations between seasonal variation, climate factors, and AA flare frequency in pediatric AA patients, we performed a retrospective chart review of 123 pediatric AA patients at Brown Dermatology (Providence, Rhode Island) who experienced hair loss between January 2017 and December 2019. We assessed association of seasonal variation with monthly occurrence of AA flares. We then assessed association between climate variables and monthly AA hair loss frequency using Spearman rank correlation analyses. We conducted stratified analyses in patients with and without history of atopy. The greatest proportion of hair loss episodes occurred in winter (28.1%), followed by autumn (26.3%), spring (23.8%), and summer (21.7%). We found significant correlations between AA hair loss frequency and air pressure (R = 0.61) and hours of sunlight (R = − 0.60). These correlations remained significant among patients with no history of atopic disease but were not significant among those with history of atopy. Limitations include small sample size. This regional analysis supports the role of climate in AA hair loss episodes through assessment of seasonal occurrences and identification of correlations between climate characteristics and AA flare frequency.

A severe case of COVID-19 was observed in an otherwise healthy 28-year-old man who had taken oxandrolone 40 mg/day as an anabolic steroid. The patient had been taking oxandrolone for enhanced bodybuilding 30 days prior to presenting to an outpatient clinic with COVID-19 symptoms. The patient reported that his symptoms have rapidly worsened over the course of 4 days prior to presenting at the clinic. As part of an experimental antiandrogen treatment for hyperandrogenic men suffering from COVID-19, he was administered a single 600 mg dose of the novel antiandrogen proxalutamide. Twenty-four hours after administration of this dose, marked improvement of symptoms and markers of disease severity were observed. To our knowledge, this is the first case that potentially links anabolic steroid use to COVID-19 disease severity.

Background Rheumatoid arthritis (RA) is a systemic autoimmune condition characterized by erosive inflammation of the joints. One rare pulmonary manifestation is obliterative bronchiolitis (OB), a small airways disease characterized by the destruction of bronchiolar epithelium and airflow obstruction. Methods We retrospectively reviewed the clinical data of patients with rheumatoid arthritis-associated obliterative bronchiolitis (RA-OB) from 01/01/2000 to 12/31/2015. Presenting clinical features, longitudinal pulmonary function testing, radiologic findings, and independent predictors of all-cause mortality were assessed. Results Forty one patients fulfilled criteria for diagnosis of RA-OB. There was notable female predominance (92.7%) with a mean age of 57 ± 15 years. Dyspnea was the most common presenting clinical symptom. Median FEV1 was 40% (IQR 31–52.5) at presentation, with a mean decline of − 1.5% over a follow-up period of thirty-three months. Associated radiologic findings included mosaic attenuation and pulmonary nodules. A majority of patients (78%) received directed therapy including long-acting inhalers, systemic corticosteroids or other immunosuppressive agents, and macrolide antibiotics. All-cause mortality was 27% over a median follow-up of sixty-two months (IQR 32–113). No distinguishable predictors of survival at presentation were found. Conclusions RA-OB appears to have a stable clinical course in the majority of patients despite persistent symptoms and severe obstruction based on presenting FEV1.

While immunotherapy shows great promise in patients with triple negative breast cancer, many will not respond to treatment. Radiotherapy has the potential to prime the tumor-immune microenvironment for immunotherapy. However, predicting response is difficult due to tumor heterogeneity across patients, which necessitates personalized medicine strategies that incorporate tumor tracking into the therapeutic approach. Here, we investigated the use of ultrasound (US) imaging of the tumor vasculature to monitor the tumor response to treatment. We utilized ultrafast power doppler US to track the vascular response to radiotherapy over time. We used 4T1 (metastatic) and 67NR (non-metastatic) breast cancer models to determine if US measurements corroborate conventional immunostaining analysis of the tumor vasculature. To evaluate the effects of radiation, tumor volume and vascular index were calculated using US, and the correlation between vascular changes and immune cell infiltration was determined. US tumor measurements and the quantified vascular response to radiation were confirmed with caliper measurements and immunostaining, respectively, demonstrating a proof-of-principle method for non-invasive vascular monitoring. Additionally, we found significant infiltration of CD8 T cells into irradiated tumors 10 days after radiation, which followed a sustained decline in vascular index and an increase in splenic CD8 T cells that was first observed 1 day post-radiation. Our findings reveal that ultrafast power doppler US can evaluate changes in tumor vasculature that are indicative of shifts in the tumor-immune microenvironment. This work may lead to improved patient outcomes through observing and predicting response to therapy.