TGF-β1 mediates hypoxia-preconditioned olfactory mucosa mesenchymal stem cells improved neural functional recovery in Parkinson's disease models and patients.

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear.

Differentiation Syndrome in a Patient With NSCLC Harboring Mutation Treated With Enasidenib: Case Report.

gain-of-function mutations cause DNA hypermethylation interfering with cellular differentiation and are linked to poor disease outcomes in NSCLC. inhibitor enasidenib is approved for refractory acute myeloid leukemia but has been associated with delayed onset of differentiation syndrome-a potentially fatal inflammatory reaction caused by differentiating agents, namely all-trans retinoic acid and arsenic trioxide. We report the first case of differentiation syndrome in a patient with NSCLC treated with enasidenib, who after 7 weeks experienced bilateral peripheral edema and shortness of breath, with scans exhibiting pericardial effusion and ground-glass opacities suggestive of pneumonitis.

Discovery of a signaling feedback circuit that defines interferon responses in myeloproliferative neoplasms.

Interferons (IFNs) are key initiators and effectors of the immune response against malignant cells and also directly inhibit tumor growth. IFNα is highly effective in the treatment of myeloproliferative neoplasms (MPNs), but the mechanisms of action are unclear and it remains unknown why some patients respond to IFNα and others do not. Here, we identify and characterize a pathway involving PKCδ-dependent phosphorylation of ULK1 on serine residues 341 and 495, required for subsequent activation of p38 MAPK.

Association of HLA class I homozygosity with unfavorable clinical outcomes in patients with non-small cell lung cancer treated with chemo-immunotherapy or immunotherapy as first-line therapy.

Background: Homozygosity at HLA-I locus has been reported to be an unfavorable predictive biomarker of second-line or beyond immunotherapy in patients with different types of cancer. The linkage between HLA-I zygosity and survival in NSCLC patients treated with first-line immunotherapy with or without chemotherapy has not been reported.

Methods: Next generation sequencing with HLA genotyping was performed on patients with advanced NSCLC treated with immune checkpoint inhibitors with or without chemotherapy as first-line (N = 29).

Avenues Toward microRNA Detection : A Review of Technical Advances and Challenges.

Over the decades, the biological role of microRNAs (miRNAs) in the post-transcriptional regulation of gene expression has been discovered in many cancer types, thus initiating the tremendous expectation of their application as biomarkers in the diagnosis, prognosis, and treatment of cancer. Hence, the development of efficient miRNA detection methods is in high demand. Extensive efforts have been made based on the intrinsic properties of miRNAs, such as low expression levels, high sequence homology, and short length, to develop novel miRNA detection methods with high accuracy, low cost, practicality, and multiplexity at point-of-care settings.

Proliferation saturation index in an adaptive Bayesian approach to predict patient-specific radiotherapy responses.

Radiotherapy prescription dose and dose fractionation protocols vary little between individual patients having the same tumor grade and stage. To personalize radiotherapy a predictive model is needed to simulate radiation response. Previous modeling attempts with multiple variables and parameters have been shown to yield excellent data fits at the cost of non-identifiability and clinically unrealistic results.

Culture-Negative Periprosthetic Joint Infection: An Update on What to Expect.

Background: Culture-negative periprosthetic joint infection (PJI) is a challenging condition to treat. The most appropriate management of culture-negative PJI is not known, and there is immense variability in the treatment outcome of this condition. The purpose of this study was to elucidate the characteristics, outcomes, and risk factors for failure of treatment of culture-negative PJI.

Highly Effective and Low-Cost MicroRNA Detection with CRISPR-Cas9.

MicroRNAs have been reported as related to multiple diseases and have potential applications in diagnosis and therapeutics. However, detection of miRNAs remains improvable, given their complexity, high cost, and low sensitivity as of currently. In this study, we attempt to build a novel platform that detects miRNAs at low cost and high efficacy.

Diagnosing Periprosthetic Joint Infection: And the Winner Is?

Background: Diagnosis of periprosthetic joint infection (PJI) remains a challenge despite a wide variety of available diagnostic tests. The question that arises is which of these tests has a better performance for diagnosing PJI. Diagnostic odds ratio (DOR) has been described as the best indicator for test performance.

Vancomycin Prophylaxis for Total Joint Arthroplasty: Incorrectly Dosed and Has a Higher Rate of Periprosthetic Infection Than Cefazolin.

Background: In total joint arthroplasty (TJA), vancomycin is used as perioperative antibiotic prophylaxis in patients with penicillin allergy or in patients colonized with methicillin-resistant Staphylococcus aureus (MRSA). Although vancomycin dosing should be weight-based (15 mg/kg), not all surgeons are aware of this; a fixed 1-g dose is instead frequently administered.

Questions/purposes: (1) Is there a difference in the risk of periprosthetic joint infection (PJI) in patients receiving vancomycin or cefazolin prophylaxis after primary TJA? (2) What proportion of patients is adequately dosed with vancomycin? (3) Compared with actual fixed dosing, does weight-based dosing result in a greater proportion of patients staying above the recommended 15-mg/L level at the beginning and end of surgery? (4) Are patients overdosed with vancomycin at greater risk of developing nephrotoxicity and acute kidney injury?

Methods: A single-institution, retrospective study was performed on 1828 patients undergoing primary TJAs who received vancomycin prophylaxis between 2008 and 2014.

Polymicrobial Periprosthetic Joint Infections: Outcome of Treatment and Identification of Risk Factors.

Background: The treatment outcomes of periprosthetic joint infection are frequently dependent on characteristics of the causative organism. The objective of this comparative study was to investigate the prevalence of and risk factors for development of polymicrobial periprosthetic joint infection, and the outcome of surgical treatment of these patients.

Methods: All patients with polymicrobial, monomicrobial, or culture-negative periprosthetic joint infection treated from 2000 to 2014 were identified at a single institution.

Chronic Kidney Disease Linearly Predicts Outcomes After Elective Total Joint Arthroplasty.

Background: Kidney disease is associated with increased complications in total joint arthroplasty (TJA). The purpose of this study was to determine the association of kidney disease severity as measured by the chronic kidney disease (CKD) staging system with complications after TJA.

Methods: A retrospective review of 12,308 primary TJAs (6361 hips and 5947 knees) from 2008 to 2013 was performed.