The short- and long-term effect of osteopathic manipulative treatment on pain, and psychosocial factors in adults with chronic low back pain.

CONTEXT: Chronic low back pain (CLBP) has long plagued mankind, but little progress has been made in finding a rational and effective treatment, let alone a common cause. This study is an attempt to fill that void by measuring short- and long-term effects of osteopathic manipulative treatment (OMT), including psychosocial and pain reduction in CLBP patients. OBJECTIVES: The objectives of this study were to investigate the effectiveness of neuromusculoskeletal medicine/osteopathic manipulative medicine (OMM) in treating CLBP, with a focus on biopsychosocial (pain sensitivity questionnaire [PSQ]) and pain control in chronic conditions. METHODS: The study involved a large, single cohort observational design of 101 patients. The inclusion criteria for selecting patients targeted those with "nonspecific" CLBP. The National Institutes of Health (NIH) Minimum Dataset for Chronic Low Back Pain (NMD) was the measurement tool and was administered at consent (baseline), 2, 4, and 8 weeks and at 6 and 12 months. Time trends were analyzed as overall mean. Pairwise differences were compared between time points. Mixed-effects models were utilized to test the association of time with pain and biopsychosocial scores. RESULTS: Pain and PSQ scores decreased over the study timeline. The most significant change for both pain and biopsychosocial scores occurred at 6 months compared to baseline, with a further reduction at 12 months. CONCLUSIONS: OMT has been demonstrated to significantly reduce pain and psychosocial factors related to CLBP in both the short and long term.

Revisiting chronic low back pain: evidence that it is not non-specific.

CONTEXT: There is a common symptom pattern with most chronic low back pain (CLBP), suggesting that there is a common underlying etiology, belying the term "nonspecific." Many studies of CLBP and its treatment have been conducted with the assumption of nonspecificity, and as a result, treatment has not been focused, thus there has not been a significant change in CLBP prevalence over the past several decades. It is the thesis of this study to show that there is an underlying, specific cause of CLBP and that the presumption that CLBP is nonspecific is misdirected. The lumbosacropelvic (LSP) region, including the sacroiliac joint (SIJ), is part of a neuromusculoskeletal (NMSK) feedback system, and it is proposed here that CLBP is the result of a change in the feedback (afferent) aspect in that system. OBJECTIVES: The objectives of this study are to show that CLBP presents as a pattern of symptoms that actually represents the final common pathway for a dysfunctional LSP joint system. Rather than being "nonspecific," the majority of CLBP has an underlying cause that is quite specific and predictable. METHODS: A total of 252 patients were seen for CLBP, 67% of whom were diagnosed with an SIJ dysfunction. The presence of pain was recorded from seven structures most closely associated with CLBP. The conditional probabilities of having each pain generator given a SIJ dysfunction and an SIJ dysfunction given the presence of the pain generator were estimated, and associations were analyzed utilizing chi-square tests. Phi coefficients and odds ratios were utilized to quantify the strength of the association. The multivariable logistic regression model was fit to relate the presence or absence of the SIJ dysfunction to the seven pain generators. RESULTS: The associations between SIJ dysfunction and each pain generator were statistically significant. Phi coefficients indicated moderate strengths of these bivariate associations. Iliolumbar ligament (ILL) and psoas muscle (PSM) were significant predictors of SIJ dysfunction in the multivariable model. CONCLUSIONS: Seven pain generators had a strong association with SIJ dysfunction. This empirical clinical evidence supports our hypothesis that LSP system dysfunction, as evidenced by SIJ dysfunction, is a common source of symptom patterning associated with CLBP and is most likely the causal element. This is evidence that most CLBP is not "nonspecific" but rather the result of changes made by the NMSK control system for the LSP region.

Alpelisib Efficacy in Hormone Receptor-Positive HER2-Negative PIK3CA-Mutant Advanced Breast Cancer Post-Everolimus Treatment.

This real-world cohort analysis assessed the efficacy of alpelisib and endocrine treatment (ET) combinations in a post-everolimus setting. Thirteen women who started alpelisib and ET at standard doses between 2018 and 2022 for advanced breast cancer (ABC), after undergoing CDK4/6i and everolimus treatment, were eligible for the study entry. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR) and clinical benefit rate (CBR), with different molecular profiling. The patients had previously received a median of four (range 3-8) systemic treatments, including CDK4/6i and everolimus. The median PFS on alpelisib was 5.5 months (range 0.5-10), and four women each had an ORR and three (23%) had a stable disease. The 6-month CBR was 46.1%, similar to the BYLeive study cohort C (47.8%). Notably, our cohort included patients with a long CBR under everolimus treatment (median 6 months, range 1-18); however, the responses to alpelisib and everolimus were not correlated (Pearson r = -0.23, p = 0.44). The PIK3CA, P53, ARID, GATA3, and ESR1 mutations were not associated with the 6-month CBR. Despite heavy pre-treatments, including everolimus, alpelisib was clinically relevant in our cohort, even among patients with an ESR1 mutation. The best treatment sequence for PIK3CA/mTOR inhibitors warrants examination in future trials on PIK3CA-mutant inpatients with luminal ABC.

The association between geriatric assessment, muscle measures, and treatment-related toxicity in older adults with cancer: An Israeli prospective study.

INTRODUCTION: We investigated the associations among frailty, as determined via the comprehensive geriatric assessment (CGA), muscle measures (i.e., sarcopenia), and treatment-related toxicity in older adults with cancer in Israel. MATERIALS AND METHODS: This prospective cohort study enrolled patients ≥65 years with newly-diagnosed stage IV lung, breast, or genitourinary cancer. Patients were enrolled and completed CGA before their first line of systemic therapy (chemotherapy, biologic therapy, immunologic therapy, or a combination thereof). CGA was used to classify patients as robust, pre-frail, or frail, and routine pre-treatment computed tomography (CT) images were used to quantify skeletal muscle index (SMI) and skeletal muscle density (SMD) at L3 cross-section. Two sarcopenia definitions were used: i. for women SMI <41 cm2/m2 regardless of body mass index (BMI), and for men SMI <43 cm2/m2 for those with BMI of <25 and < 53 cm2/m2 for those with BMI ≥25; and ii. SMI <38 cm2/m2 for women and < 41 cm2/m2 for men, regardless of BMI. The associations between frailty and muscle measures with the occurrence of at least one adverse event (AE) grade ≥ 2 were examined using the chi-square test, and logistic regression to determine odds ratio (OR) and 95% confidence interval (CI). RESULTS: In total, 51 patients were included in the analysis. The median (interquartile range) age was 72 (68-76) years, 30 (59%) were male, and 26 (51%) had lung cancer. CGA data were available for 48 patients: fifteen (31%), thirteen (27%), and twenty (42%) were defined as robust, pre-frail, and frail, respectively. Overall, 33 (65%) were sarcopenic by the first aforementioned definition, and sixteen (31%) by the second. No statistically significant associations were identified between frailty and having at least one AE grade ≥ 2, or between frailty and sarcopenia. Statistically significant associations were found between having sarcopenia (the second definition) and having at least one AE grade ≥ 2 (P = 0.0217). The corresponding odds ratio (95% CI) was 4.2 (1.2-15.0), P = 0.026. DISCUSSION: Our findings suggests that sarcopenia is significantly associated with treatment-related toxicity. Further studies with larger sample sizes are warranted.

Prospective Comparison of Geriatric Assessment and Provider's Assessment of Older Adults With Metastatic Breast Cancer in the Community.

BACKGROUND: Geriatric assessment (GA) is recommended for evaluating fitness of an older adult with cancer. Our objective was to prospectively evaluate the gaps that exist in the assessment of older adults with metastatic breast cancer (OA-MBC) in community practices (CP). METHODS: Self-administered GA was compared to provider's assessment (PA) of patients living with MBC aged ≥65 years treated in CP Providers were blinded to the GA results until PA was completed. McNemar's test was used to detect differences between PA and GA. RESULTS: One hundred patients were enrolled across 9 CP (median age 73.9). Geriatric assessment detected a total of 356 abnormalities in 96 patients; of which, 223 required interventions. African American and widowed/single patients were more likely to have abnormalities identified by GA. On average, across 100 patients, PA did not detect 25.5% of GA-detected abnormalities, mostly in functional status, social support, nutrition, and cognition. These differences were less pronounced among providers with more clinical experience. Patients with abnormal Timed Up and Go tests more likely had additional abnormalities in other domains, and more abnormalities that were not identified by PA. Providers were "surprised" by GA results in 33% of cases, mainly with cognitive or social support findings, and reported plans for management change for 39% of patients based on GA findings. CONCLUSIONS: Including a GA in the care of OA-MBC in CP is beneficial for the detection of multiple abnormalities not detected by routine PA.

Promoting Strategies to Increase HPV Vaccination in the Pediatric Primary Care Setting.

INTRODUCTION: Evaluation of a quality improvement project designed to improve HPV vaccine uptake in a pediatric primary care setting for young adolescents. METHOD: Three strategies were implemented in one private pediatric practice to promote HPV vaccine uptake for 11- and 12-year-old adolescents. 1) a standardized vaccine policy change was made to include HPV vaccine with other adolescent vaccines, 2) a pre-visit email was sent to parents of teens to provide factual vaccine information in preparation for the visit, and 3) a provider communication initiative was implemented to ensure all providers communicated consistent messages and delivered an effective cancer prevention recommendation for HPV vaccination. A pre/post design was used to compare vaccine rates. Data was obtained via the electronic health records. RESULTS: The post-intervention group demonstrated HPV vaccine rates increased substantially from 17.8% to 63.6%. DISCUSSION: Strategically implementing standardized clinical vaccine policies and presumprive provider communication practices has implications for significantly increasing HPV vaccine uptake among teens and may be key to preventing cancer among future generations.

Cardiovascular complications of mantle field radiation: a case series.

BACKGROUND: Mantle field radiotherapy has been known to cause cardiovascular complications even years after therapy. Complications include pericardial disease, coronary artery disease, and conduction abnormalities. CASE SUMMARY: We present a case series of two patients who developed cardiovascular complications years after receiving mantle radiation. Patient 1 is a 52-year-old man who presented with symptoms of heart failure. He had a neurostimulator which precluded him from cardiac magnetic resonance imaging. Haemodynamic findings on right heart catheterization raised suspicion for constrictive pericarditis and pericardiectomy was performed. Histopathological analysis reported dense, sclerotic fibrous tissue consistent with radiation-related changes. Patient 2 is a 37-year-old man with a 2-month history of chest pain and exertional dyspnoea who was admitted for management of coronary artery disease. Coronary angiography demonstrated bilateral subclavian artery stenosis and an elevated left ventricular end-diastolic pressure (50 mmHg). He had bilateral percutaneous subclavian artery stenting. Both patients had complete resolution of symptoms on follow-up. DISCUSSION: Our case series emphasizes the need for an index of suspicion for radiation-related cardiovascular changes in patients who have a history of mantle radiation, especially in younger patients. This was especially pertinent in the case of our first patient who presented a diagnostic challenge due to certain patient factors. Our second patient is a case of subclavian artery stenosis which is less frequently reported as a complication of mantle radiation in the literature.

Anti-infection silver nanoparticle immobilized biomaterials facilitated by argon plasma grafting technology.

Many research groups have attained slow, persistent, continuous release of silver ions through careful experimental design using existing methods. Such methods effectively kill planktonic bacteria and therefore prevent surface adhesion of pathogens. However, the resultant modified coatings cannot provide long-term antibacterial efficacy due to sustained anti-microbial release. In this study, the anti-infection activity of AgNP immobilized biomaterials was evaluated, facilitated by argon plasma grafting technology and activated by bacterial colonization. The modified materials generated in this study showed excellent specificity and were active against both Gram-positive and Gram-negative biofilm forming bacteria, including methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli. The anti-infection biomaterials developed in this study demonstrate several attractive advantages in comparison to traditional anti-bacterial surfaces loaded with antibiotics or other types of antibacterial agents and include (1) broad spectrum of activity against antibiotic resistant bacteria, (2) the unlikelihood of bacterial resistance, (3) specificity, (4) biocompatibility, and (5) stability.

The Escherichia coli baby cell column: a novel cell synchronization method provides new insight into the bacterial cell cycle.

We describe a new method for synchronizing bacterial cells. Cells that have transiently expressed an inducible mutant 'sticky' flagellin are adhered to a volume of glass beads suspended in a chromatography column though which growth medium is pumped. Following repression of flagellin synthesis, newborn cells are eluted from the column in large quantities exceeding that of current baby machine techniques by approximately 10-fold. Eluted cultures of 'baby cells' are highly synchronous as determined by analysis of DNA replication, cell division and other events, over time after elution from the column. We also show that use of 'minutes after elution' as a time metric permits much greater temporal resolution among sequential chromosomal events than the commonly used metric of cell size (length). The former approach reveals the existence of transient intermediate stages that are missed by the latter approach. This finding has two important implications. First, at a practical level, the baby cell column is a particularly powerful method for temporal analysis. Second, at a conceptual level, replication-related events are more tightly linked to cell birth (i.e. cell division) than to absolute cell mass.