Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus.

Intestinal commensal bacteria can inhibit dense colonization of the gut by vancomycin-resistant Enterococcus faecium (VRE), a leading cause of hospital-acquired infections1,2. A four-strained consortium of commensal bacteria that contains Blautia producta BPSCSK can reverse antibiotic-induced susceptibility to VRE infection3. Here we show that BPSCSK reduces growth of VRE by secreting a lantibiotic that is similar to the nisin-A produced by Lactococcus lactis. Although the growth of VRE is inhibited by BPSCSK and L. lactis in vitro, only BPSCSK colonizes the colon and reduces VRE density in vivo. In comparison to nisin-A, the BPSCSK lantibiotic has reduced activity against intestinal commensal bacteria. In patients at high risk of VRE infection, high abundance of the lantibiotic gene is associated with reduced density of E. faecium. In germ-free mice transplanted with patient-derived faeces, resistance to VRE colonization correlates with abundance of the lantibiotic gene. Lantibiotic-producing commensal strains of the gastrointestinal tract reduce colonization by VRE and represent potential probiotic agents to re-establish resistance to VRE.

Demographic differences in early vs. late-stage laryngeal squamous cell carcinoma.

PURPOSE: This study aims to evaluate how various demographic factors impact the stage at diagnosis and, therefore, prognosis of laryngeal cancer. MATERIALS AND METHODS: Using the National Cancer Database, 96,409 patients were diagnosed with laryngeal squamous cell carcinoma between 2004 and 2020. Early (stage 0 or I) vs. late-stage (stage IV) cancers were compared based on demographic variables utilizing Chi-square and multivariate analysis with a significance of p < 0.05. RESULTS: Female, Black, and generally older patients were more likely to have late-stage cancer than their counterparts. When compared with a community cancer program, patients treated at other facility types were more likely to be diagnosed late. Patients with private insurance, Medicare, or other government insurance were all less likely to have late-stage cancer compared to patients without insurance. Compared to patients in the lowest median household income quartile, patients in the third quartile and fourth quartile were diagnosed earlier. Patients living in an area with the lowest level of high school degree attainment were most likely to be diagnosed late. Living in a more populous area was associated with a lower chance of being diagnosed late. Increasing Charlson-Deyo Score was associated with a stronger likelihood of being diagnosed at a later stage. CONCLUSION: Patients who are female, Black, uninsured, have a low household income, live in less populated and less educated areas, are treated at non-community cancer programs, and have more comorbid conditions have later stage diagnoses. This data contributes to understanding inequities in healthcare.

Assessing the Safety and Efficacy of Tranexamic Acid Usage in Osteogenesis Imperfecta Patients.

BACKGROUND: Osteogenesis Imperfecta (OI) usually causes an increased fracture burden and bone deformity, with subsequent operations common. In addition to skeletal manifestations, there is a potential increase in bleeding susceptibility due to the increased frequency of orthopedic procedures, warranting investigation into methods to mitigate this risk. This study aims to evaluate the safety and efficacy of tranexamic acid (TXA) usage to reduce intraoperative blood loss in children with OI. We want to assess the potential benefits, risks, and complications involved with TXA use in this patient population. METHODS: TXA-receiving patients (cases) were matched 1:1 with non-TXA-receiving controls on the following criteria: age within 2 years, bone category, and OI Type. Descriptive statistics were used to summarize the data. Fisher Exact Test was performed to compare transfusion status between groups. A Wilcoxon Rank Sum test was performed to assess differences between the groups in days of stay, length of surgery, and estimated blood loss (EBL). All analyses were conducted using SAS version 9.4. P <0.05 was considered statistically significant. RESULTS: Our TXA-receiving population of 30 patients consisted of 11 females and 19 males. One patient was OI type I, 13 were OI type III, 14 were OI type IV, and 2 were categorized as Other (not Type I through Type IV). We found a significant difference in transfusion status ( P =0.02), with zero TXA patients requiring a transfusion compared with 20% of the control cases. There is also a significant difference in median EBL ( P =0.0004) between groups, with TXA patients having decreased intraoperative EBL (20 vs. 62.5 mL). There was also a difference in median days of postoperative stay between TXA-receiving and non-TXA-receiving patients ( P =0.001; 2.6 vs. 4 d). CONCLUSIONS: Our study concluded that TXA use in OI patients is associated with lower perioperative transfusions and intraoperative blood loss rates. These results support the standard usage of TXA in these patients to reduce intraoperative blood loss. LEVEL OF EVIDENCE: Level III.

Extent of Surgery and Survival of Osteosarcoma: A Retrospective Population-Based Study.

Background Osteosarcoma (OSC) is the most common primary bone tumor and is often managed surgically. Few prior investigations have assessed differences in OSC survival by specific surgical techniques at a national registry level. We sought to compare survival based on surgical subtypes for OSC patients in the Surveillance, Epidemiology, and End Results (SEER) database. Methodology We searched the SEER database for malignant OSCs diagnosed between 2000 and 2019 which were surgically managed. Separate survival comparisons were made for one and five years for wide excision (local tumor destruction or resection versus partial resection) and radical excision (radical resection with limb-sparing versus limb amputation with or without girdle resection). Results A total of 4,303 patients were included, of whom 3,587 were surgically managed. There were no survival differences between local destruction and partial resection (hazard ratio = 0.826, p = 0.303). However, younger age, lower staging, and management without radiation were associated with improved survival. The radical excision comparison showed limb amputation was associated with worse survival than limb-sparing surgery (hazard ratio = 1.531, p < 0.001). Younger age, female sex, lower stage, receipt of chemotherapy, and neoadjuvant plus adjuvant chemotherapy were associated with improved survival while Black and American Indian or Alaska Native were associated with worse survival. Conclusions Our findings show that patients managed with limb-sparing radical resection survived significantly compared to limb amputation. There were no differences in survival for wide excision surgeries. The use of a combination of neoadjuvant and adjuvant chemotherapy also yields improved survival. OSC survival may be optimized with limb-sparing surgery with a combination of neoadjuvant and adjuvant chemotherapy.

Utilization of Palliative Care in Osteosarcoma: A National Cancer Database Review.

Background: Osteosarcoma is the most common form of bone cancer, but the utilization of palliative care (PC) in patients with this cancer has not previously been investigated in the National Cancer Database (NCDB). Methods: Patients diagnosed with osteosarcoma (2004-2017) were identified within the NCDB. Cross tabulations with Chi-square analysis were performed to evaluate frequencies of palliative care use by patient, facility, and tumor characteristics. Multivariate logistic binary regression was performed to evaluate relationships between patient, treatment facility, and tumor characteristics and the use of palliative care. Results: A total of 7498 patients were analyzed with 2.8% of patients diagnosed having any form of palliative care utilization. Of this group, 53.37% received PC within the first 12 months after diagnosis. Of the 2.8% of patients receiving PC the most common forms of PC utilized were non-curative symptom-directed surgery, radiation, or chemotherapy, or a combination of these modalities (56.7%). Palliative care usage was increased in patients with greater tumor diameter, tumors in the bones of the midline, or stage IV tumors. Palliative care usage was decreased in patients living within 25-49 miles of their treatment facility, those living in pacific states, those with chondroblastic osteosarcoma, or those with private insurance. Conclusion: Palliative care use in patients with osteosarcoma increases with tumor stage, tumor size, or more proximal tumors, but overall utilization remains markedly low. Future studies should further define these patterns of care and help expand the utilization of PC.

Survey of Palliative Care Use in Primary Malignant Bone Tumors: A National Cancer Database Review.

Background/Objectives: Palliative care (PC) has been associated with reduced patient symptom burden, improved physician satisfaction, and reduced cost of care. However, its use in primary bone tumors has not been well classified. Design/Setting and Subjects: Patients diagnosed with primary malignant bone tumors (osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma) between 2004 and 2018 were identified in the National Cancer Database. Cross tabulations with chi-square analysis were performed to evaluate frequencies of PC use by patient, facility, and tumor characteristics. Multivariate logistic binary regression was performed to evaluate relationships between patient, treatment facility, and tumor characteristics and the use of PC. Results: Around 24,401 patients were identified. Overall, 2.52% had any form of PC utilization. Of those receiving PC, 55.5-65.1% were treated with only noncurative surgery, radiation, chemotherapy, or any combination of these modalities. Odds of PC utilization were decreased for patients with chordomas, patients living >24 miles from the treatment facility, or patients with private insurance, Medicare, or unknown insurance status. Odds of PC utilization were increased in patients with greater tumor diameter or unknown tumor size, tumors in midline, increased tumor grade, stage IV tumors, or living in urban areas. Conclusion: PC use in patients with primary bone tumors increases with tumor stage, tumor grade, tumor size, and if the tumor is midline, and in patients living in urban areas. However, overall utilization remains markedly low. Future studies should be done to investigate these patterns of care and help expand the utilization of PC.

Odds of Stage IV Bone Cancer Diagnosis Based on Socioeconomic and Geographical Factors: A National Cancer Database (NCDB) Review.

BACKGROUND: There are significant differences in prognosis for osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordomas based on the stage at diagnosis. The five-year survival of these bone cancers varies from 75-87% at an early stage of diagnosis and falls to 27-55% at a late stage of diagnosis. PATIENTS AND METHODS: This study retrospectively evaluated the odds of stage I vs stage IV cancer at the time of diagnosis in patients with primary malignant bone tumors (osteosarcoma, chondrosarcoma, Ewing sarcoma and chordoma) diagnosed in the National Cancer Database (NCDB) between 2004 and 2018. Cross tabulations with Chi-square analysis were performed to evaluate frequencies of different socioeconomic and geographical characteristics between patients with stage I vs stage IV cancer. Multivariable binary logistic regression was performed to evaluate relationships between socioeconomic and geographical factors and the odds of stage IV cancer at the time of diagnosis. Statistical significance was set at α = 0.05. RESULTS: 8882 patients with stage I and 3063 with stage IV primary malignant bone tumors were identified. The odds of stage IV bone cancer at diagnosis are increased for patients on Medicaid (odds ratio [OR] = 1.298, 95% confidence interval [CI]: 1.043-1.616) or Medicare (OR = 1.795, 1.411-2.284). Odds of stage IV bone cancer at diagnosis were decreased with female sex (OR = 0.733, 0.671-0.800), private insurance (OR = 0.738, 0.601-0.905), and those treated at community cancer programs (OR = 0.542, 0.369-0.797), comprehensive cancer program (OR = 0.312, 0.215-0.452), or academic/research facilities (OR = 0.370, 0.249-0.550). No significant relationship was identified between the stage at diagnosis and race, ethnicity, Charlson-Deyo score, or education level. Stage IV cancer at diagnosis showed was proportionally lower in chondrosarcomas (17.1%) and chordomas (2.1%) than osteosarcomas (45.0%) and Ewing sarcomas (35.8%). CONCLUSION: Odds of stage IV bone cancer at diagnosis are greater with male sex, Medicaid or Medicare insurance status, or treatment at community cancer programs. Providers should have a low suspicion for additional evaluation when treating patients with symptoms of bone cancer and should be aware of these disparities when treating people in these groups. This is to the authors' knowledge the first such study conducted through the NCDB.

Effects of Socioeconomic and Geographic Factors on Outcomes in Ewing Sarcoma: A National Cancer Database Review.

PURPOSE: Ewing sarcoma is a primary malignant bone tumor that manifests predominantly in the proximal long bones and pelvis and traditionally presents with nonspecific symptoms. This tumor preferentially affects children and young adults, occurring most often in patients of European descent. The most important established prognostic factor is the presence of metastasis at the time of diagnosis followed by primary site, size of the primary neoplasm, patient age, and lactate dehydrogenase (LDH) levels. To the authors' knowledge, this is the first study focused on the effects of socioeconomic and geographic factors on overall survival in Ewings sarcoma. METHODS: A total of 3,920 patients diagnosed with Ewing sarcoma were identified in the National Cancer Database (NCDB) using the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) code 9260. Of these, 3,238 met the inclusion criteria and were analyzed. Descriptive statistics, Kaplan-Meier survival curves, and Cox regression tables were all performed using IBM SPSS Statistics for Windows, Version 27.0 (Released 2020; IBM Corp., Armonk, New York, United States). RESULTS: Univariate analysis showed greater mortality for patients of increasing age at the time of diagnosis, at two, five, and 10 years of follow-up, Black race patients at two years, Medicare insurance status at two years, urban or rural residence at two and 10 years, more advanced tumor stage at two and five years, and patients with a comorbidity score of ≥2 at two years. Multivariate analysis showed greater mortality at two years with increasing age, Black race, uninsured status, urban or rural residence, and increasing tumor stage. Mortality also increased for patients at five years of follow-up in patients with increasing age or more advanced tumor stage.  Conclusion: Patient mortality in the first two years after diagnosis is increased for patients of the Black race, those living in urban or rural areas, and for patients that are uninsured or using Medicare as their primary payor at the time of diagnosis. To improve patient outcomes, clinicians should recognize and address not only the unique biology of patients but also their unique challenges in access to healthcare. Patients and providers should work to elicit changes on an individual and community level to improve their personal health and the health of those around them.

YouTube and the Achilles Tendon: An Analysis of Internet Information Reliability and Content Quality.

PURPOSE: To evaluate the educational content, quality, and reliability of YouTube videos regarding the Achilles tendon and Achilles tendon injuries. METHODS: The first 50 videos found on YouTube after searching "Achilles tendon" were evaluated and classified by content type and uploader source. Reliability and accuracy were assessed using the Journal of the American Medical Association (JAMA) benchmark criteria, nonspecific educational content was assessed via the Global Quality Score (GQS), and specific educational content was assessed using the Achilles Tendon Specific Score (ATSS). ANOVA was performed to determine differences in video reliability and educational content quality by video content type and source. Multivariate stepwise regressions were used to evaluate the effects of specific video characteristics on JAMA benchmark criteria, GQS, and ATSS. RESULTS: The 50 videos evaluated had a cumulative view total of 53,323,307, a mean of 1,066,466, and a range of 1,009 to 42,663,665 views per video. Most videos focused on disease-specific information (38%) and exercise training (22%). Most videos were uploaded by non-physicians (34%) or medical sources (health websites) (32%). A higher view ratio was an independent predictor of lower JAMA scores (lower reliability and accuracy) (standardized beta = -0.281, P = 0.048) and increased video duration was an independent predictor of greater GQS (standardized beta = 0.380, P = 0.007) and ATSS scores (standardized beta = 0.364, P = 0.009) (increased quality of nonspecific and specific educational content). CONCLUSION: Videos on YouTube regarding the Achilles tendon were viewed numerous times, but their educational content and reliability were poor. Providers treating patients for Achilles tendon-related pathologies should initiate a dialogue with patients about their use of internet sources and should educate them on their optimal usage. They should warn them of the low quality of YouTube-derived information and provide them with reliable sources that may better give them control over their own care.

Analysis of Negative Reviews of Orthopedic Oncology Surgeons: An Investigation of Reviews from Healthgrades, Vitals, and Google.

Background: Physician review websites (PRWs) are increasing in usage and popularity. Our purpose is to characterize one-star reviews of orthopedic oncology surgeons to understand factors in healthcare that contribute to patient satisfaction. Methods: Orthopedic oncology surgeons were randomly selected from the Musculoskeletal Tumor Society. A search for one-star reviews was performed on Google Reviews, Healthgrades, and Vitals.com. Reviews were classified as clinical or nonclinical. Statistical analyses were performed regarding the frequency of reviews and complaints for each category. Results: Of the 7,733 reviews discovered, 908 (11.7%) were identified as one-star reviews. Of 907 usable complaints, 362 (40.8%) were clinical and 545 (59.2%) were nonclinical. The most common nonclinical complaints included bedside manner (65%) and limited time with providers (19%). The most common clinical complaints included complications (26%) and disagreements with the treatment plan (26%). There were 120 surgical and 221 nonsurgical reviews. Surgical patients had a higher rate of clinical complaints. Nonsurgical patients had a higher rate of total complaints. Conclusion: To the best of our knowledge, this is the first study examining PRWs regarding orthopedic oncology surgeons. Most one-star reviews were due to nonclinical complaints from nonsurgical patients. The most common factors are bedside manner, limited time with provider, phone communication issues, and rude/unprofessional conduct.

Functional and Genomic Variation between Human-Derived Isolates of Lachnospiraceae Reveals Inter- and Intra-Species Diversity.

Bacteria belonging to the Lachnospiraceae family are abundant, obligate anaerobic members of the microbiota in healthy humans. Lachnospiraceae impact their hosts by producing short-chain fatty acids, converting primary to secondary bile acids, and facilitating colonization resistance against intestinal pathogens. To increase our understanding of genomic and functional diversity between members of this family, we cultured 273 Lachnospiraceae isolates representing 11 genera and 27 species from human donors and performed whole-genome sequencing assembly and annotation. This analysis revealed substantial inter- and intra-species diversity in pathways that likely influence an isolate's ability to impact host health. These differences are likely to impact colonization resistance through lantibiotic expression or intestinal acidification, influence host mucosal immune cells and enterocytes via butyrate production, or contribute to synergism within a consortium by heterogenous polysaccharide metabolism. Identification of these specific functions could facilitate development of probiotic bacterial consortia that drive and/or restore in vivo microbiome functions.