CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21^lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21^lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21^lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21^lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

     

Prediction of early (4-week) mortality in acute myeloid leukemia with intensive chemotherapy

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m² during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was divided into a training (2790 patients) and a validation cohort (938 patients). The median age was 55 years (range, 15-99). Among them, 442 patients (12%) had core-binding factor AML. Binary logistic regression identified older age, worse performance status, hyperbilirubinemia, elevated creatinine, hyperuricemia, cytogenetic abnormalities other than CBF and -Y, and pneumonia as adverse prognostic factors for an early 4-week mortality. This risk classification for early mortality was verified in the validation cohort of patients. In the validation cohort of more recently treated patients from 2000 to 2017, the 4-week mortality rates with intensive chemotherapy were 2%, 14%, and 50% in the low-, high-, and very high-risk group, respectively. The mortality rates with low intensity therapies were 3%, 9%, and 20%, respectively. The risk classification guides treatment intensity by the assessment of age, frailty, organ dysfunction, cytogenetic abnormality, and infection to avoid early mortality.     

A contemporary systematic review on liver transplantation for unresectable liver metastases of colorectal cancer

The 5-year overall survival rate of a patient with unresectable metastatic colorectal cancer is poor at approximately 14%. Similarly, historical data on liver transplantation (LT) in those with colorectal liver metastases (CRLM) showed poor outcomes, with 5-year survival rates between 12% and 21%. More recently, limited data have shown improved outcomes in select patients with 5-year overall survival rates of approximately 60%. Despite these reported survival improvements, there is no significant improvement in disease-free survival. Given the uncertain benefit with this therapeutic approach and a renewed investigational interest, we aimed to conduct a contemporary systematic review on LT for CRLM. A systematic review of the literature was performed according to the preferred reporting items for systematic reviews and meta-analysis statement. English articles reporting on data regarding LT for CRLM were identified through the MEDLINE (via PubMed), Cochrane Library, and ClinicalTrials.gov databases (last search date: December 16th, 2021) by 2 researchers independently. A total of 58 studies (45 published and 13 ongoing) were included. Although early retrospective studies suggest the possibility that some carefully selected patients may benefit from LT, there is minimal prospective data on the topic and LT remains exploratory in the setting of CRLM. Additionally, several other challenges, such as the limited availability of deceased donor organs and defining appropriate selection criteria, remain when considering the implementation of LT for these patients. Further evidence from ongoing prospective trials is needed to determine if and to what extent there is a role for LT in patients with surgically unresectable CRLM.     

Alternatives to remifentanil for the analgesic component of total intravenous anaesthesia: a narrative review

Propfol-remifentanil-based total intravenous anaesthesia has dominated recent clinical practice due to its favourable pharmacokinetic profile. Interruption in remifentanil supply has presented an opportunity to diversify or even avoid the use of opioids and consider adjuncts to propofol-based total intravenous anaesthesia. Propofol, while a potent hypnotic, is not an effective analgesic. The administration of opioids, along with other adjuncts such as α-2 adrenoceptor agonists, magnesium, lidocaine, ketamine and nitrous oxide provide surgical anaesthesia and avoids large doses of propofol being required. We provide an overview of both target-control and manual infusion regimes for the alternative opioids: alfentanil, sufentanil and fentanyl. The optimal combination of hypnotic-opioid dose, titration sequence and anticipated additional postoperative analgesia required depend on the chosen combination. In addition, we include a brief discussion on the role of non-opioid adjuncts in total intravenous anaesthesia, suggested doses and expected reduction in propofol dose.     

Correction to: Disease burden and treatment sequence of polymyositis and dermatomyositis patients in Japan: a real-world evidence study

Clinical Rheumatology -     

DEep learning-based rapid Spiral Image REconstruction (DESIRE) for high-resolution spiral first-pass myocardial perfusion imaging

The objective of the current study was to develop and evaluate a DEep learning-based rapid Spiral Image REconstruction (DESIRE) technique for high-resolution spiral first-pass myocardial perfusion imaging with whole-heart coverage, to provide fast and accurate image reconstruction for both single-slice (SS) and simultaneous multislice (SMS) acquisitions. Three-dimensional U-Net–based image enhancement architectures were evaluated for high-resolution spiral perfusion imaging at 3 T. The SS and SMS MB = 2 networks were trained on SS perfusion images from 156 slices from 20 subjects. Structural similarity index (SSIM), peak signal-to-noise ratio (PSNR), and normalized root mean square error (NRMSE) were assessed, and prospective images were blindly graded by two experienced cardiologists (5: excellent; 1: poor). Excellent performance was demonstrated for the proposed technique. For SS, SSIM, PSNR, and NRMSE were 0.977 [0.972, 0.982], 42.113 [40.174, 43.493] dB, and 0.102 [0.080, 0.125], respectively, for the best network. For SMS MB = 2 retrospective data, SSIM, PSNR, and NRMSE were 0.961 [0.950, 0.969], 40.834 [39.619, 42.004] dB, and 0.107 [0.086, 0.133], respectively, for the best network. The image quality scores were 4.5 [4.1, 4.8], 4.5 [4.3, 4.6], 3.5 [3.3, 4], and 3.5 [3.3, 3.8] for SS DESIRE, SS L1-SPIRiT, MB = 2 DESIRE, and MB = 2 SMS-slice-L1-SPIRiT, respectively, showing no statistically significant difference (p = 1 and p = 1 for SS and SMS, respectively) between L1-SPIRiT and the proposed DESIRE technique. The network inference time was ~100 ms per dynamic perfusion series with DESIRE, while the reconstruction time of L1-SPIRiT with GPU acceleration was ~ 30 min. It was concluded that DESIRE enabled fast and high-quality image reconstruction for both SS and SMS MB = 2 whole-heart high-resolution spiral perfusion imaging.     

Initial assessment of α-synuclein structure in platelets

Journal of Thrombosis and Thrombolysis - Over the last few years data from our group have indicated that α-synuclein is important in development of immune cells as well as potentially...