Outcomes and Complications Associated With the Learning Curve for Endoscopic Cervical Foraminotomy: A Systematic Review and Meta-Analysis.

STUDY DESIGN: A systematic review and meta-analysis. OBJECTIVE: The objective of this study is to examine the impact of the learning curve for endoscopic cervical foraminotomy for clinical outcomes and patient safety. SUMMARY OF BACKGROUND DATA: Endoscopic cervical foraminotomy is a minimally invasive surgical technique emerging in the literature for surgical management of cervical radiculopathy without the use of open incision. The adoption of endoscopic cervical foraminotomy may be hindered by the learning curve, although no review and meta-analysis exists to date on the topic. MATERIALS AND METHODS: A systematic review and meta-analysis was performed using PubMed, CINAHL, and MEDLINE from database inception until July 11, 2023. Inclusion criteria were articles that examined endoscopic cervical foraminotomy, reported outcomes, and/or complications for endoscopic cervical spine surgery relevant to the learning curve and had full-text. A random effects meta-analysis was performed for outcomes and complications. RESULTS: A total of three articles (n=203 patients) were included from 792 articles initially retrieved. The learning curves from four surgeons were examined with a FWM 21 procedures until the competency phase. There was no significant difference in the postoperative hospitalization length ( P =0.669), postoperative recovery room time ( P =0.415), intraoperative blood loss ( P =0.064), and total complication rates (10.9% vs . 1.2%, P =0.139) between endoscopic cervical foraminotomy procedures performed in the learning phase as compared with the competency phase of the learning curve. There was a significant decrease in operative time from the learning phase to the competency phase ( P =0.005). CONCLUSION: Competency was achieved on the learning curve for endoscopic cervical foraminotomy after about 21 procedures. There is no significant difference in postoperative hospitalization time, postoperative recovery room time, intraoperative blood loss, and complication rates between the learning phase and the competency phase of the learning curve for endoscopic cervical foraminotomy, noting the relatively small sample size of this study that may underpower this finding.

Comparing Outcomes After Referral to Physical Therapy for Patients With Glenohumeral Osteoarthritis Based on the Radiographic Osteoarthritis Severity: A Retrospective Analysis.

Introduction Glenohumeral osteoarthritis (GHOA) is a common cause of musculoskeletal pain (MSP) that can frequently lead to pain and functional disability in patients throughout the world. GHOA can be managed with conservative or surgical interventions, although conservative interventions, such as physical therapy (PT), are generally first-line interventions depending on the severity of GHOA. The purpose of this retrospective analysis was to examine how conventional PT impacts outcomes for patients with GHOA based on the severity of radiographic GHOA findings. Methods This study is a retrospective chart review of patients who were referred to PT for MSP and received PT in the outpatient setting between 2016 and 2022. Inclusion criteria were patients who received PT in the outpatient setting, received PT for MSP, had shoulder radiograph imaging within two years of initial PT evaluation, had more than one PT visit (i.e. attended a follow-up session after initial evaluation), and did not have a history of shoulder surgery. Primary outcome measures were pain, abduction active range-of-motion (AROM), and disability via the quick disabilities of the arm, shoulder, and hand (DASH). Patients were divided into the No GHOA group (n=104), Mild GHOA group (n=61), and Moderate/Severe GHOA group (n=55) based on the radiographic GHOA severity. Results All included patients (n=220) had a mean age of 62.2 ± 12.4 years old with a mean number of PT visits of 7.8 ± 4.5 visits. There was initially a significant difference in the magnitude of pain improvement between the three groups based on radiographic severity of GHOA (Kruskal-Wallis H=6.038; p=0.049); however, post hoc testing revealed no significant difference between any of the three groups for pain improvement (p=0.061 to p=1.000). There was also no significant difference in the magnitude of abduction AROM improvement between the three groups based on the radiographic severity of GHOA (Kruskal-Wallis H=2.887; p=0.236). Finally, there was no significant difference in the magnitude of disability improvement via the Quick DASH between the three groups based on the radiographic severity of GHOA (Kruskal-Wallis H=0.156; p=0.925). Conclusion Patients with GHOA referred to PT experience small but statistically significant short-term improvements in pain, abduction AROM, and disability regardless of GHOA radiographic severity. There is no significant association between the magnitude of clinical improvement and the severity of radiographic GHOA. However, despite statistically significant improvements in pain, only patients with mild GHOA experienced clinically significant improvements in pain. Patients with GHOA, regardless of severity, may or may not experience clinically significant improvements in disability after PT.

Clinical Outcomes Associated With the Addition of a Physical Therapist Assistant to a Rehabilitation Team When Treating Musculoskeletal Shoulder Pain in the Outpatient Setting: A Retrospective Cohort Study.

Introduction Musculoskeletal shoulder pain (MSP) is a common condition frequently treated in an outpatient setting by a physical therapy rehabilitation team. Treatment teams can consist of physical therapists (PTs) with or without physical therapist assistants (PTAs). It is currently unknown how different physical therapy team compositions can impact patient outcomes in the outpatient setting. The purpose of this study is to examine how the addition of PTAs to a physical therapy treatment team would impact clinical outcomes when treating patients with MSP in the outpatient setting. Methods This study is a retrospective cohort analysis comparing clinical outcomes for pain, active range of motion (AROM), and disability for patients with MSP when treated by physical therapy treatment teams with or without the presence of PTAs. Inclusion criteria were patients treated for MSP in an outpatient physical therapy clinic without a history of shoulder surgery. Depending on the rehabilitation team composition, patients were divided into a PT-only group or a PTA group. Results Total patients (n = 238) had a mean age of 62.6 ± 12.6 years (median: 64 years) with a mean total number of physical therapy visits of 7.8 ± 4.9 visits (median: 7.0 visits). Of the entire cohort, the PT-only group had 100 patients and the PTA group had 138 patients. There was no significant difference in the magnitude of pain improvement (mean: 1.5 versus 1.9 points, p = 0.177), the magnitude of abduction AROM improvement (mean: 17.6 versus 13.9 degrees, p = 0.173), and the magnitude of disability improvement (mean: 18.9 versus 13.4 percentage points, p = 0.221) between the PT-only group and the PTA group. However, the PT-only group had significantly fewer total visits as compared to the PTA group (6.7 versus 8.6 visits, p < 0.001). Conclusion The addition of PTAs to a rehabilitation team when treating patients with MSP in the outpatient setting does not appear to adversely impact pain, AROM, or disability outcomes. However, patients treated only by PTs had significantly less visits with similar outcomes. More research is needed to determine the interplay between cost, healthcare utilization, and patient outcomes to maximize quality care.

Dissecting the Rat Mammary Gland: Isolation, Characterization, and Culture of Purified Mammary Epithelial Cells and Fibroblasts.

With the advent of CRISPR-Cas and the ability to easily modify the genome of diverse organisms, rat models are being increasingly developed to interrogate the genetic events underlying mammary development and tumorigenesis. Protocols for the isolation and characterization of mammary epithelial cell subpopulations have been thoroughly developed for mouse and human tissues, yet there is an increasing need for rat-specific protocols. To date, there are no standard protocols for isolating rat mammary epithelial subpopulations. Analyzing changes in the rat mammary hierarchy will help us elucidate the molecular events in breast cancer, the cells of origin for breast cancer subtypes, and the impact of the tumor microenvironment. Here we describe several methods developed for 1) rat mammary epithelial cell isolation; 2) rat mammary fibroblast isolation; 3) culturing rat mammary epithelial cells; and characterization of rat mammary cells by 4) flow cytometric analysis; and 5) immunofluorescence. Cells derived from this protocol can be used for many purposes, including RNAseq, drug studies, functional assays, gene/protein expression analyses, and image analysis.

NF1 deficiency correlates with estrogen receptor signaling and diminished survival in breast cancer.

The key negative regulatory gene of the RAS pathway, NF1, is mutated or deleted in numerous cancer types and is associated with increased cancer risk and drug resistance. Even though women with neurofibromatosis (germline NF1 mutations) have a substantially increased breast cancer risk at a young age and NF1 is commonly mutated in sporadic breast cancers, we have a limited understanding of the role of NF1 in breast cancer. We utilized CRISPR-Cas9 gene editing to create Nf1 rat models to evaluate the effect of Nf1 deficiency on tumorigenesis. The resulting Nf1 indels induced highly penetrant, aggressive mammary adenocarcinomas that express estrogen receptor (ER) and progesterone receptor (PR). We identified distinct Nf1 mRNA and protein isoforms that were altered during tumorigenesis. To evaluate NF1 in human breast cancer, we analyzed genomic changes in a data set of 2000 clinically annotated breast cancers. We found NF1 shallow deletions in 25% of sporadic breast cancers, which correlated with poor clinical outcome. To identify biological networks impacted by NF1 deficiency, we constructed gene co-expression networks using weighted gene correlation network analysis (WGCNA) and identified a network connected to ESR1 (estrogen receptor). Moreover, NF1-deficient cancers correlated with established RAS activation signatures. Estrogen-dependence was verified by estrogen-ablation in Nf1 rats where rapid tumor regression was observed. Additionally, Nf1 deficiency correlated with increased estrogen receptor phosphorylation in mammary adenocarcinomas. These results demonstrate a significant role for NF1 in both NF1-related breast cancer and sporadic breast cancer, and highlight a potential functional link between neurofibromin and the estrogen receptor.

Bovine milk derived skimmed milk powder and whey protein concentrate modulates Citrobacter rodentium shedding in the mouse intestinal tract.

Skimmed milk powder (SMP) and whey protein concentrate (WPC) were manufactured from fresh milk collected from cows producing high or low Immunoglobulin (Ig) A levels in their milk. In addition commercial products were purchased for use as diluent or control treatments. A murine enteric disease model (Citrobacter rodentium) was used to assess whether delivery of selected bioactive molecules (IgA, IgG, Lactoferrin (Lf)) or formulation delivery matrix (SMP, WPC) affected faecal shedding of bacteria in C. rodentium infected mice. In trial one, faecal pellets collected from mice fed SMP containing IgA (0.007-0.35 mg/mL), IgG (0.28-0.58 mg/mL) and Lf (0.03-0.1 mg/mL) contained fewer C. rodentium (cfu) compared to control mice fed water (day 8, p < 0.04, analysis of variance (ANOVA) followed by Fisher's unprotected least significant difference (ULSD)). In trial two, WPC containing IgA (0.35-1.66 mg/mL), IgG (0.58-2.36 mg/mL) and Lf (0.02-0.45 mg/mL) did not affect C. rodentium shedding, but SMP again reduced faecal C. rodentium levels (day 12, p < 0.04, ANOVA followed by Fisher's ULSD). No C. rodentium was detected in sham phosphate-buffered saline inoculated mice. Mice fed a commercial WPC shed significantly greater numbers of C. rodentium over 4 consecutive days (Fishers ULSD test), compared to control mice fed water. These data indicate that SMP, but not WPC, modulates faecal shedding in C. rodentium-infected mice and may impact progression of C. rodentium infection independently of selected bioactive concentration. This suggests that food matrix can impact biological effects of foods.

Comparative innate immune interactions of human and bovine secretory IgA with pathogenic and non-pathogenic bacteria.

Secretory IgA (SIgA) from milk contributes to early colonization and maintenance of commensal/symbiotic bacteria in the gut, as well as providing defence against pathogens. SIgA binds bacteria using specific antigenic sites or non-specifically via its glycans attached to α-heavy-chain and secretory component. In our study, we tested the hypothesis that human and bovine SIgA have similar innate-binding activity for bacteria. SIgAs, isolated from human and bovine milk, were incubated with a selection of commensal, pathogenic and probiotic bacteria. Using flow cytometry, we measured numbers of bacteria binding SIgA and their level of SIgA binding. The percentage of bacteria bound by human and bovine SIgA varied from 30 to 90% depending on bacterial species and strains, but was remarkably consistent between human and bovine SIgA. The level of SIgA binding per bacterial cell was lower for those bacteria that had a higher percentage of SIgA-bound bacteria, and higher for those bacteria that had lower percentage of SIgA-bound bacteria. Overall, human and bovine SIgA interacted with bacteria in a comparable way. This contributes to longer term research about the potential benefits of bovine SIgA for human consumers.

Transfer of intestinal bacterial components to mammary secretions in the cow.

Results from large multicentre epidemiological studies suggest an association between the consumption of raw milk and a reduced incidence of allergy and asthma in children. Although the underlying mechanisms for this association are yet to be confirmed, researchers have investigated whether bacteria or bacterial components that naturally occur in cow's milk are responsible for modulating the immune system to reduce the risk of allergic diseases. Previous research in human and mice suggests that bacterial components derived from the maternal intestine are transported to breast milk through the bloodstream. The aim of our study was to assess whether a similar mechanism of bacterial trafficking could occur in the cow. Through the application of culture-independent methodology, we investigated the microbial composition and diversity of milk, blood and feces of healthy lactating cows. We found that a small number of bacterial OTUs belonging to the genera Ruminococcus and Bifidobacterium, and the Peptostreptococcaceae family were present in all three samples from the same individual animals. Although these results do not confirm the hypothesis that trafficking of intestinal bacteria into mammary secretions does occur in the cow, they support the existence of an endogenous entero-mammary pathway for some bacterial components during lactation in the cow. Further research is required to define the specific mechanisms by which gut bacteria are transported into the mammary gland of the cow, and the health implications of such bacteria being present in milk.

The acute-phase protein serum amyloid A3 is expressed in the bovine mammary gland and plays a role in host defence.

The serum amyloid A protein is one of the major reactants in the acute-phase response. Using representational difference analysis comparing RNA from normal and involuting quarters of a dairy cow mammary gland, we found an mRNA encoding the SAA3 protein (M-SAA3). The M-SAA3 mRNA was localized to restricted populations of bovine mammary epithelial cells (MECs). It was expressed at a moderate level in late pregnancy, at a low level through lactation, was induced early in milk stasis, and expressed at high levels in most MECs during mid to late involution and inflammation/mastitis. The mature M-SAA3 peptide was expressed in Escherichia coli, antibodies made, and shown to have antibacterial activity against E. coli, Streptococcus uberis and Pseudomonas aeruginosa. These results suggest that the mammary SAA3 may have a role in protection of the mammary gland during remodelling and infection and possibly in the neonate gastrointestinal tract.

First incursion of Salmonella enterica serotype typhimurium DT160 into New Zealand.

An outbreak of human Salmonella enterica serotype Typhimurium DT160 infection in New Zealand was investigated from May to August 2001. Handling of dead wild birds, contact with persons with diarrheal illness, and consumption of fast food were associated with infection. Contaminated roof-collected rainwater was also detected.