Does Paraspinal Muscle Mass Predict Lumbar Lordosis before and after Decompression for Degenerative Spinal Stenosis?

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: The purpose of this study was to determine if muscle mass and quality of the lumbar paraspinal muscles was associated with improvements in lumbar lordosis and other sagittal parameters after isolated posterior lumbar decompression surgery for lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA: Over time, either due to degenerative changes or other spinal conditions, individuals may develop sagittal imbalance. In patients with lumbar spinal stenosis, sagittal imbalance can further exacerbate symptoms of pain and radiculopathy. Sarcopenia of paraspinal muscles has been implicated in previous spine research as a variable with influence on surgical outcomes. METHODS: Sagittal parameters were measured on preoperative and postoperative lateral lumbar radiographs and included lumbar lordosis (LL), sacral slope (SS), and pelvic tilt (PT). Preoperative MRI images were evaluated at the base of the L4 vertebral body to assess muscles mass of the psoas muscle and paravertebral muscles (PVM) and Goutallier grade of the PVM. Patients were divided into 3 muscle size groups based on PVM normalized for body size (PVM/BMI): Group A (smallest), Group B, and Group C (largest). RESULTS: Patients in Group C had greater LL preoperatively (51.5° vs. 47.9° vs. 43.2, P=0.005) and postoperatively (52.2° vs. 48.9° vs. 45.7°, P=0.043). There was no significant difference in the ∆LL values between groups (P>0.05). Patients in Group C had larger SS preoperatively (35.2° vs. 32.1° vs. 30.0°, P=0.010) and postoperatively (36.1° vs. 33.0° vs. 31.7°, P=0.030). Regression analysis showed that PVM/BMI was a significant predictor of LL preoperatively (P=0.039) and postoperatively (P=0.031), as well as SS preoperatively (P=0.001) and postoperatively (P<0.001). CONCLUSION: Muscle mass of the paravertebral muscles significantly impacts lumbar lordosis and sacral slope in patients with lumbar spinal stenosis before and after posterior lumbar decompression. These findings highlight a need to address risk factors for poor muscle quality in patients with sagittal imbalance.

The Implication of Preoperative Central Stenosis on Patient-Reported Outcomes After Lumbar Decompression Surgery.

OBJECTIVE: To assess the impact of central stenosis severity on patient-reported outcomes after lumbar decompression. METHODS: Patient diagnosis, demographics, and surgical characteristics were collected via query search and manual chart review of electronic medical records. The inclusion criteria were posterior lumbar decompressions from 2014-2020, with accessible magnetic resonance imaging reports. As previously validated by Lee et al., central stenosis was determined on magnetic resonance imaging and graded as none, mild, moderate, or severe. Patients were dichotomized into 2 groups to improve statistical power for comparisons: none or mild central stenosis and moderate or severe central stenosis. Patient-reported outcome measures (PROMs) were compared between cohorts at 1 year postoperatively. Statistical significance was set at P < 0.05. RESULTS: On bivariate analysis, no significant differences were noted between cohorts with regard to preoperative, 1-year postoperative, and delta PROMs. In addition, no significant difference in the number of patients attaining minimal clinically important difference (MCID) for each PROM was noted between cohorts. With the exception of mental score of the Short Form-12 survey, all intragroup preoperative to postoperative PROMs indicated significant improvement (all P < 0.05) after lumbar decompression surgery. Multivariate regression identified moderate or severe central canal stenosis as a significant independent predictor of improvement in visual analog scale back (estimate = -1.464, P = 0.045). CONCLUSIONS: We demonstrate that patients with moderate or severe central spinal stenosis may have more improvement in back pain than those with mild or no central stenosis after lumbar spine decompression surgery.

Mucoadhesive Ionic Liquid Gel Patches for Oral Delivery.

Oral delivery of biologic drugs is a highly desired yet challenging goal because of the many barriers posed by the GI tract. Ionic liquids (ILs) and deep eutectic solvents (DESs) such as choline and geranate (CAGE) have demonstrated the potential to improve intestinal absorption of insulin and poorly soluble drugs. As with other delivery agents, localization of the ILs in the intestine can enhance the delivery potential by increasing local concentrations while maintaining low off-target concentrations, thus improving the therapeutic window of the ILs. Here, we describe a method of encapsulating CAGE into a gel using PVA, forming a mucoadhesive ionogel patch (CAGE-patch) designed to adhere to the intestine. CAGE-patches formed via repeated freeze-thaw cycles demonstrated mucoadhesive strength, swelling, and controlled release of both CAGE and insulin. In vitro transport studies revealed a more than 30% increase in insulin transport when compared to controls across Caco-2 and HT29-MTX-E12 coculture layers. This design provides a novel approach to localize ionic liquids and therapeutics in the GI tract for enhanced oral delivery.

Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome.

Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, we quantified SARS-CoV-2 viral load, analysed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response. Acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium). Increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality. Our data provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2.

Modulation of Gastrointestinal Mucus Properties with Ionic Liquids for Drug Delivery.

The mucus barrier lining the gastrointestinal tract poses a significant barrier to the oral delivery of macromolecular drugs. Successful approaches to overcoming this barrier have primarily focused on reducing drug and carrier interactions with mucus or disrupting the mucus layer directly. Choline-based ionic liquids (ILs) such as choline geranate and choline glycolate (CGLY) have recently been shown to be effective in enhancing the intestinal absorption of macromolecules such as insulin and immunoglobulin (IgG), respectively. Herein, the use of choline-based ILs as mucus-modulating agents for safely improving drug penetration through mucus is described. Choline-based ILs significantly increase the diffusion rates of cationic dextrans through mucin solution. Choline-maleic acid (CMLC 2:1) enhances the diffusion of 4 kDa cationic dextran in mucin solution by more than fourfold when compared to phosphate-buffered saline control. Choline-based ILs also reduce mucus viscosity without significantly impacting the native mucus gel structure. In vitro studies in a mucus-secreting coculture model with Caco-2 and HT29MTX-E12 cells further demonstrate the effectiveness of ILs in improving transport of cationic molecules in the presence of secreted mucus. This work demonstrates the potential for choline-based ionic liquids to be used as nondestructive mucus-modulating agents for enabling enhanced oral delivery of macromolecular drugs.

Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome.

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.

Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome.

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.