Evaluation of the safety profile and intrapulmonary pharmacokinetics of intravenous fosfomycin in healthy adults.

Unlabelled: This Phase 1 trial described the intrapulmonary pharmacokinetics and safety profile of IV fosfomycin in healthy participants Fosfomycin, a broad-spectrum antibiotic mainly used to treat urinary tract infections, is being considered for treatment of more complex conditions, including lung infections, due to the emergence of multidrug-resistant (MDR) organisms. Despite its potential, the pharmacokinetics and safety profile of intravenous (IV) fosfomycin, particularly its penetration into the lower respiratory tract, are unknown. To address this gap, we conducted a Phase 1, open-label trial to assess the safety and pulmonary pharmacokinetics of IV fosfomycin in healthy participants.

Clinical Utility of Plasma Microbial Cell-Free DNA Sequencing Among Immunocompromised Patients With Pneumonia.

Background: Plasma microbial cell-free DNA (mcfDNA) sequencing can establish the etiology of multiple infectious syndromes by identifying microbial DNA in plasma. However, data are needed to define the clinical scenarios where this tool offers the highest clinical benefit.

Methods: We conducted a prospective multicenter observational study that evaluated the impact of plasma mcfDNA sequencing compared with usual care testing among adults with hematologic malignancies.

Cost-Effectiveness of Plasma Microbial Cell-Free DNA Sequencing When Added to Usual Care Diagnostic Testing for Immunocompromised Host Pneumonia.

Introduction: Immunocompromised host pneumonia (ICHP) is an important cause of morbidity and mortality, yet usual care (UC) diagnostic tests often fail to identify an infectious etiology. A US-based, multicenter study (PICKUP) among ICHP patients with hematological malignancies, including hematological cell transplant recipients, showed that plasma microbial cell-free DNA (mcfDNA) sequencing provided significant additive diagnostic value.

Aim: The objective of this study was to perform a cost-effectiveness analysis (CEA) of adding mcfDNA sequencing to UC diagnostic testing for hospitalized ICHP patients.

Using Augmented Reality Technology to Optimize Transfacet Lumbar Interbody Fusion: A Case Report.

The transfacet minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is a novel approach available for the management of lumbar spondylolisthesis. It avoids the need to manipulate either of the exiting or traversing nerve roots, both protected by the bony boundaries of the approach. With the advancement in operative technologies such as navigation, mapping, segmentation, and augmented reality (AR), surgeons are prompted to utilize these technologies to enhance their surgical outcomes.

Osteoimmunology: Interactions With the Immune System in Spinal Fusion.

Spinal fusion is important for the clinical success of patients undergoing surgery, and the immune system plays an increasingly recognized role. Osteoimmunology is the study of the interactions between the immune system and bone. Inflammation impacts the osteogenic, osteoconductive, and osteoinductive properties of bone grafts and substitutes and ultimately influences the success of spinal fusion.

Surgical technique of combined minimally invasive anterior column realignment at L1-L2 with open extension of prior fusion.

Surgical correction of fixed kyphotic deformity or severe sagittal imbalance traditionally involves three column osteotomies, which are associated with high morbidity rates. Anterior column realignment (ACR) has emerged as a minimally invasive alternative for restoring segmental lordosis. This technique involves a lateral approach and release of the anterior longitudinal ligament (ALL), followed by placement of a hyperlordotic interbody cage.

Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Patients With Pneumonia: A Prospective Observational Study.

Background: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia.

Methods: In this prospective, multicenter, observational study of immunocompromised adults undergoing bronchoscopy to establish a pneumonia etiology, plasma microbial cell-free DNA sequencing was compared to standardized usual care testing.

Measuring Outcomes in Spinal Deformity Surgery.

Outcome assessment in adult spinal deformity has evolved from radiographic analysis of curve correction to patient-centered perception of health-related quality-of-life. Oswestry Disability Index and the Scoliosis Research Society-22 Patient Questionnaire are the predominantly used patient-reported outcome (PRO) measurements for deformity surgery. Correction of sagittal alignment correlates with improved PRO.

Characteristics of patients who return to work after undergoing surgery for cervical spondylotic myelopathy: a Quality Outcomes Database study.

Objective: Return to work (RTW) is an important surgical outcome for patients who are employed, yet a significant number of patients with cervical spondylotic myelopathy (CSM) who are employed undergo cervical spine surgery and fail to RTW. In this study, the authors investigated factors associated with failure to RTW in the CSM population who underwent cervical spine surgery and who were considered to have a good surgical outcome yet failed to RTW.

Methods: This study retrospectively analyzed prospectively collected data from the cervical myelopathy module of a national spine registry, the Quality Outcomes Database.

Interferon gamma mediates the reduction of adipose tissue regulatory T cells in human obesity.

Decreased adipose tissue regulatory T cells contribute to insulin resistance in obese mice, however, little is known about the mechanisms regulating adipose tissue regulatory T cells numbers in humans. Here we obtain adipose tissue from obese and lean volunteers. Regulatory T cell abundance is lower in obese vs.

Sacroiliac Joint Fusion Using Robotic Navigation: Technical Note and Case Series.

Background: Patients undergoing sacroiliac (SI) fusion can oftentimes experience significant improvements in pain and quality of life.

Objective: To describe a novel application of robotic navigation to assist with minimally invasive SI joint fusion.

Methods: Patients undergoing stand-alone SI joint fusion with ExcelsiusGPS robotic navigation from July 2020 through June 2021 were retrospectively enrolled.

Successful Neonatal, Intraoperative Neuromonitoring in the Surgical Correction of a Thoracic Dermal Sinus Tract: Technical Note.

Introduction: Intraoperative neuromonitoring (IONM) is commonly used during surgery of the spine and spinal cord for early surveillance of iatrogenic injury to the central and peripheral nervous system. However, for infants and young children under 3 years of age, the use of IONM is challenging due to incomplete central and peripheral myelination.

Case Presentation: We report a case of a T4-T6 dermal sinus tract (DST) that was resected on day of life 23, with the successful use of IONM.

Pseudarthrosis rate following anterior cervical discectomy with fusion using an allograft cellular bone matrix: a multi-institutional analysis.

Objective: The use of osteobiologics, engineered materials designed to promote bone healing by enhancing bone growth, is becoming increasingly common for spinal fusion procedures, but the efficacy of some of these products is unclear. The authors performed a retrospective, multi-institutional study to investigate the clinical and radiographic characteristics of patients undergoing single-level anterior cervical discectomy with fusion performed using the osteobiologic agent Osteocel, an allograft mesenchymal stem cell matrix.

Methods: The medical records across 3 medical centers and 12 spine surgeons were retrospectively queried for patients undergoing single-level anterior cervical discectomy and fusion (ACDF) with the use of Osteocel.

Environmental activation of a hypothalamic BDNF-adipocyte IL-15 axis regulates adipose-natural killer cells.

Physical and social environments influence immune homeostasis within adipose tissue, yet the mechanisms remain poorly defined. We report that an enriched environment (EE) housing modulates the immune cell population in white adipose tissue of mice including an increase in the abundance of natural killer (NK) cells. EE upregulates the expression of IL-15 and its receptor IL-15Rα specifically within mature adipocytes.

Enriched environment enhances NK cell maturation through hypothalamic BDNF in male mice.

Macroenvironmental factors, including a patient's physical and social environment, play a role in cancer risk and progression. Our previous preclinical studies have shown that the enriched environment (EE) confers anti-obesity and anti-cancer phenotypes that are associated with enhanced adaptive immunity and are mediated by brain-derived neurotrophic factor (BDNF). Natural killer (NK) cells have anti-cancer and anti-viral properties, and their absence or depletion is associated with inferior clinical outcomes.

Perioperative Assessment of Cerebellar Masses and the Potential for Cerebellar Cognitive Affective Syndrome.

The cerebellum was long perceived to be a region of limited importance with primary functions in the regulation of motor control. A degree of its functional topography in motor modulation has been traditionally appreciated. However, an evolving body of evidence supports its role in a range of cognitive processes, including executive decision making, language, emotional processing, and working memory.

Obesogenic Memory Maintains Adipose Tissue Inflammation and Insulin Resistance.

Background: Obesity is characterized by visceral adipose tissue (AT) inflammation. Immunosuppressive regulatory T cells (Tregs), phagocytic M2-like macrophages, and innate lymphoid cells type 2 (ILC2) control lean AT inflammation to maintain systemic insulin sensitivity, while the loss of these cells in obesity leads to AT inflammation and insulin resistance (IR).

Objective: The objective of this study was to determine if weight loss following obesity would correct AT inflammation and systemic metabolism.

Ablation of the Brca1-Palb2 Interaction Phenocopies Fanconi Anemia in Mice.

Heterozygous mutations in the gene predispose women to breast and ovarian cancer, while biallelic BRCA1 mutations are a cause of Fanconi anemia (FA), a rare genetic disorder characterized by developmental abnormalities, early-onset bone marrow failure, increased risk of cancers, and hypersensitivity to DNA-crosslinking agents. BRCA1 is critical for homologous recombination of DNA double-strand breaks (DSB). Through its coiled-coil domain, BRCA1 interacts with an essential partner, PALB2, recruiting BRCA2 and RAD51 to sites of DNA damage.