Deleonhorn3690

Austevoll IM, Hermansen E, Fagerland MW, Storheim K, Brox JI, Solberg T, Rekeland F, Franssen E, Weber C, Brisby H, Grundnes O, Algaard KRH, Böker T, Banitalebi H, Indrekvam K, Hellum C; NORDSTEN-DS Investigators. Decompression with or without Fusion in Degenerative Lumbar Spondylolisthesis. N Engl J Med. 2021 Aug 5;385(6)526-538.

To investigate the expression of Hedgehog (HH) signaling pathway proteins in knee articular cartilage from Kashin-Beck disease (KBD) and osteoarthritis (OA) patients.

Knee articular cartilage samples were collected from normal (N), OA, and KBD adults (aged 38-60 years) and divided into 3 groups with 6 subjects in each group. The localization of the HH pathway proteins bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 4 (BMP4), Sonic hedgehog (SHH), and Indian hedgehog (IHH) was observed with the microscope after immunohistochemical (IHC) staining. Positive staining cell rates of each proteins were compared.

The strongest stainings of all proteins were observed in the middle zones of all 3 groups. The positive staining rates of BMP4 and IHH were significantly lower in the OA and KBD groups than those in the N group in all 3 zones. The positive staining rates of BMP2 and SHH tend to be lower in the OA and KBD groups than those in the N group in the deep zone, while higher in the OA and KBD groups than those in the N group in superficial and middle zones.

Altered expression of the HH pathway proteins BMP2, BMP4, SHH, and IHH was found in OA and KBD articular cartilage. There seemed to be a compensatory effect between SHH and IHH in cartilage damage. Further studies on the pathogenesis of OA and KBD may be carried out from these aspects in the future.

Altered expression of the HH pathway proteins BMP2, BMP4, SHH, and IHH was found in OA and KBD articular cartilage. There seemed to be a compensatory effect between SHH and IHH in cartilage damage. Further studies on the pathogenesis of OA and KBD may be carried out from these aspects in the future.

Tissue-engineered cartilage implants must withstand the potential inflammatory and joint loading environment for successful long-term repair of defects. The work's objectives were to develop a novel, direct cartilage-macrophage co-culture system and to characterize interactions between self-assembled neocartilage and differentially stimulated macrophages.

In study 1, it was hypothesized that the proinflammatory response of macrophages would intensify with increasing construct stiffness; it was expected that the neocartilage would display a decrease in mechanical properties after co-culture. In study 2, it was hypothesized that bioactive factors would protect neocartilage properties during macrophage co-culture. Also, it was hypothesized that interleukin 10 (IL-10)-stimulated macrophages would improve neocartilage mechanical properties compared to lipopolysaccharide (LPS)-stimulated macrophages.

As hypothesized, stiffer neocartilage elicited a heightened proinflammatory macrophage response, increasing tuevelop the burgeoning field of cartilage mechano-immunology.

In conclusion, neocartilage stiffness can mediate macrophage behavior, but stiffness and bioactive factors prevent macrophage-induced degradation. Ultimately, this co-culture system could be utilized for additional studies to develop the burgeoning field of cartilage mechano-immunology.In this review, the authors provide an overview of erenumab, a monoclonal antibody used for the preventative treatment of episodic migraine by targeting the CGRP pathway. Randomized controlled trials have shown that erenumab is associated with a statistically significant decrease in monthly migraine days in patients with episodic migraine at monthly doses of 70 or 140 mg when given for a period of 9-12 weeks. Post hoc analyses have also shown long-term maintenance of efficacy. Clinical trials have found erenumab at doses of both 70 and 140 mg to have a favorable safety profile. Erenumab faces significant limitations because of its high financial cost. Additional long-term real-world data are needed to understand the role of erenumab in the treatment of migraine.Antibiotic resistance, particularly to carbapenems, is of increasing concern in Bacteroides fragilis. Carbapenem resistance in B. fragilis is most often mediated by the activation of chromosomally encoded metallo-β-lactamase cfiA by the presence of an upstream insertion sequence (IS). While traditional phenotypic susceptibility methods and molecular tests to detect carbapenem resistance in B. fragilis exist, they are not available in most clinical microbiology laboratory settings. Here, we describe the development of the anaerobic carbapenem inactivation method (Ana-CIM) for predicting carbapenemase production in B. fragilis based off the principles of the well-established modified carbapenem inactivation method (mCIM) for Enterobacterales and Pseudomonas aeruginosa. Selleck N6F11 We also present the clinical validation and reproducibility of the Ana-CIM at three clinical laboratory sites (with 60 clinical isolates, 45% ertapenem resistant). Compared to ertapenem susceptibility by Etest interpreted by CLSI M100 Ed30, the Ana-CIM accurately detected carbapenem resistance in B. fragilis with categorical agreement (CA) of 87% (52/60) and 0% (0/21) very major error (VME), 11% (4/36) major error (ME), and 7% (4/60) minor error (mE) rates across all sites. Additionally, the Ana-CIM demonstrated high reproducibility with 5 clinical and 3 quality control (QC) isolates tested in triplicate with 3 commercial Mueller-Hinton media across all sites, with 93% (604/648) of replicates within a 2-mm zone size of the mode for each isolate. We conclude that the Ana-CIM can be readily deployed in clinical laboratories at a low cost for detection of carbapenemase-mediated resistance in B. fragilis.The 2019 coronavirus disease (COVID-19) can present with a wide variety of clinical manifestations, including a hypercoagulable state leading to both arterial and venous thrombosis. Portal vein thrombosis (PVT) in the setting of COVID-19 has rarely been reported in the medical literature. Pylephlebitis with concomitant liver abscess is a rare complication of intra-abdominal infection. Here, we present the case of a 49-year-old man who initially presented with intermittent fevers and generalized weakness of 1-month duration and was subsequently found to have COVID-19 infection, PVT, and Bacteroides fragilis bacteremia with associated pyogenic liver abscess. The patient was treated with intravenous antibiotics and oral anticoagulation with plan to follow up outpatient with gastroenterology in 3 months to ensure resolution of PVT and liver abscess.Mesenchymal stem cells (MSCs) have been shown to exert a positive impact on osteonecrosis of the femoral head (ONFH) in preclinical experiments and clinical trials. After the femoral head suffers avascular necrosis, the transplanted MSCs undergo a great deal of stress-induced apoptosis and senescence in this microenvironment. So, survival and differentiation of MSCs in osteonecrotic areas are especially important in ONFH. Although MSCs and endothelial cells (ECs) co-culture enhancing proliferation and osteogenic differentiation of MSCs and form more mature vasculature in vivo, it remains unknown whether the co-culture cells are able to repair ONFH. In this study, we explored the roles and mechanisms of co-transplantation of angiotensin II (Ang II)-MSCs and ECs in repairing early ONFH. In vitro, when MSCs and ECs were co-cultured in a ratio of 51, both types of cells managed to proliferate and induce both osteogenesis and angiogenesis. Then, we established a rabbit model of steroid-induced ONFH and co-transplantation of Ang II-MSCs and ECs through the tunnel of core decompression. Four weeks later, histological and Western blot analyses revealed that ONFH treated with Ang II-MSCs and ECs may promote ossification and revascularization by increasing the expression of collagen type I, runt-related transcription factor 2, osteocalcin, and vascular endothelial growth factor in the femoral head. Our data suggest that co-transplantation of Ang II-MSCs and ECs was able to rescue the early steroid-induced ONFH via promoting osteogenesis and angiogenesis, which may be regarded as a novel therapy for the treatment of ONFH in a clinical setting.Primary delayed onset craniosynostosis is defined as premature suture fusion that developed despite clear radiographic evidence of normal postnatal calvarial configuration and patent sutures earlier in life. It is rare in the literature and typically presents as secondary synostosis. In this brief clinical study, primary delayed onset craniosynostosis is described in its unique presentation at 4 years of age with a complex genetic history including ERF-related craniosynostosis syndrome and familial cerebral cavernous malformation syndrome. Although the delayed onset clinical course of ERF-related craniosynostosis syndrome has not been well described in the literature, our review suggests that it is distinctive to ERF-related craniosynostosis and should be considered when cases present without a history of trauma, when there is a positive family history, and particularly when cases present late onset; after 1 year of age.Acute esophageal necrosis (AEN) is a condition characterized by black appearance and inflammation of the esophagus. Our patient developed AEN presenting in the setting of alcohol intoxication and extensive inferior vena cava thrombosis. Esophagogastroduodenoscopy showed blood and black discoloration of the middle and lower esophagus with oozing. To control bleeding, a self-expandable fully covered metallic esophageal stent was placed. Multiple studies and reviews agree that the initial management for AEN is supportive care, resuscitation, and proton pump inhibitors to protect the esophageal mucosa from injury from acid reflux. Our case highlights the benefits of esophageal stent placement to manage AEN with active bleeding.

Atrial fibrillation (AF) and heart failure (HF) frequently coexist and can be challenging to treat. Pharmacologically based rhythm control of AF has not proven to be superior to rate control. Ablation-based rhythm control was compared with rate control to evaluate if clinical outcomes in patients with HF and AF could be improved.

This was a multicenter, open-label trial with blinded outcome evaluation using a central adjudication committee. Patients with high-burden paroxysmal (>4 episodes in 6 months) or persistent (duration <3 years) AF, New York Heart Association class II to III HF, and elevated NT-proBNP (N-terminal pro brain natriuretic peptide) were randomly assigned to ablation-based rhythm control or rate control. The primary outcome was a composite of all-cause mortality and all HF events, with a minimum follow-up of 2 years. Secondary outcomes included left ventricular ejection fraction, 6-minute walk test, and NT-proBNP. Quality of life was measured using the Minnesota Living With Heart Fference of -5.4 [95% CI, -10.5 to -0.3];

=0.0036), as did the AF Effect on Quality of Life score (least-squares mean difference of 6.2 [95% CI, 1.7-10.7];

=0.0005). Serious adverse events were observed in 50% of patients in both treatment groups.

In patients with high-burden AF and HF, there was no statistical difference in all-cause mortality or HF events with ablation-based rhythm control versus rate control; however, there was a nonsignificant trend for improved outcomes with ablation-based rhythm control over rate control.

URL https//www.

gov; Unique identifier NCT01420393.

gov; Unique identifier NCT01420393.