Philadelphia College of Osteopathic Medicine
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Multiple myeloma inhibitory effects of natural compounds: enhancement through nanoparticle carriers.
Full text linkNatural compounds have emerged as promising therapeutic agents for treating cancers such as multiple myeloma (MM). However, poor bioavailability, low stability, and suboptimal targeting often limit their clinical efficacy. Recent advances in nanotechnology have addressed these limitations by utilizing nanoparticle (NP) carriers to enhance the therapeutic potential of natural compounds through improved solubility, stability, and selective delivery to cancer cells. This review explores the inhibitory effects of key natural compounds on MM cells, including 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and its derivatives, caffeic acid phenethyl ester (CAPE) and its derivatives, xanthohumol (XN) and its derivatives, resveratrol (RSV) and its derivatives, curcumin (CUR), 3,4,5-trihydroxybenzoic acid (gallic acid; GA), and evodiamine (EVO). These compounds exhibit potent anti-proliferative, pro-apoptotic, and anti-inflammatory properties through the modulation of signaling pathways such as NF-κB, STAT3, and PI3K/Akt, which are critical in MM pathogenesis. Despite their therapeutic promise, the clinical application of these natural agents has been hampered by pharmacokinetic challenges. NP carriers, including liposomes, polymeric NPs, and lipid-based nanocarriers, have been engineered to improve these compounds\u27 bioavailability and targeted delivery, enhancing their cytotoxicity against MM cells. For instance, CDDO and its derivatives encapsulated in NPs have demonstrated increased intracellular accumulation and improved inhibition of NF-κB activity. Similarly, NP formulations of CAPE, XN, and RSV have enhanced anti-MM effects through improved stability and sustained drug release. CUR, known for its poor water solubility, has seen its therapeutic potential augmented through NP delivery systems, enabling higher drug concentrations at tumor sites. Though structurally distinct, GA and EVO have benefited from NP-based enhancement, exhibiting improved bioavailability and selective targeting of MM cells. This review highlights the promising role of NP carriers in overcoming the pharmacokinetic limitations of natural compounds, offering new avenues for more effective MM therapies
Whole blood use in patients with traumatic brain injury and hemorrhagic shock is not associated with decreased mortality
No full textBACKGROUND
Traumatic brain injury (TBI) is a leading cause of trauma mortality worldwide. Whole blood (WB) is associated with decreased mortality compared with blood component therapy (BCT) alone in trauma patients with hemorrhagic shock (HS). The ideal resuscitation approach in patients with both TBI and HS remains unclear. We hypothesize that resuscitation with WB in trauma patients with TBI and HS improves mortality. METHODS
Using a prospective, multicenter, observational database, we examined a subset of patients with TBI and HS. We compared patients receiving BCT only for resuscitation with those receiving WB with BCT. We used χ2 and Kruskal-Wallis tests to compare categorical and continuous variables by the use of WB. We conducted a multivariable logistic regression to examine the association between WB and mortality controlling for shock index, Injury Severity Score, age, sex, comorbid conditions, serious head injury, and mechanism of injury. RESULTS
A total of 535 patients were included. One hundred thirty-five patients received BCT, and 400 patients received WB with BCT. There were no differences in the median Injury Severity Score, age, presence of comorbid conditions, proportion of serious head injury, or total component transfusions in the first 24 hours of admission (p \u3e 0.05). More patients in the WB group were male, in shock, and experienced blunt trauma (p \u3c 0.05). On multivariable logistic regression, WB use was not independently associated with lower mortality (odds ratio, 1.06; [95% confidence interval, 0.65-1.75]; p=0.809). CONCLUSION
We identified no in-hospital mortality benefit of WB transfusion in addition to BCT in trauma patients with TBI and HS. Further research is needed into optimal resuscitation strategies for these patients
Collaboration in Practice: Perspectives on Interprofessional Care Teams for Treating Children with Intellectual and Developmental Disabilities
Full text linkWith increased focus on interprofessional collaboration in healthcare and education, best practices for patient and student care are often top priority. However, little is known about the effectiveness of using team-based approaches when working with children with intellectual and developmental disabilities. This study examined professionals\u27 perspectives on their team practices, burnout, and attitudes towards collaboration. Additionally, the research looked at practitioners’ ability to identify their team. A survey was conducted using input from various healthcare and education professionals across multiple settings and education backgrounds who work with children with intellectual and developmental disabilities. The survey found considerable differences in team identification accuracy, perceived levels of coordination and care, and levels of burnout and attitudes towards interprofessional collaboration when compared to their own perception of their team. This study supports the rationale for creating unified definitions of care teams and the need to support professionals working with children with intellectual and developmental disabilities within care teams to help with perceived benefits and attitudes towards care coordination, which may improve provider well-being
Predictors of Mental Health Services Use in Integrated Primary Care During COVID-19
Full text linkThe purpose of this study was to identify the predisposing, need, and enabling factors that predict mental health services use before and during COVID-19 in an integrated primary care network in the Philadelphia metropolitan area. This retrospective observational study examined a sample of primary care patients from January 2018 to February 2020 (i.e., pre-COVID-19) and March 2020 to December 2022 (i.e., peri- COVID-19) using electronic health record data. Mental health services use was defined as the number of appointments attended by patients. A hierarchical regression was conducted to identify predictors of mental health services use by sequentially adding sociodemographic predisposing factors, clinical need factors, and service-level enabling factors. In the pre-COVID-19 sample (N = 1070), only Asian race and non-Hispanic White race were significant predictors but only explained 6% of the variance in mental health services use, F(9, 1060) = 7.27, p \u3c .001, R2 = .06). In the peri-Covid-19 sample (N = 2723), the final model incorporating enabling factors while controlling for predisposing and need factors accounted for an additional 1% in the variance of mental health services use, F(3, 2706) = 4.32, p = .005, R2 = .06. Findings suggest that financial status, age, Asian race, non-Hispanic White race, other race excluding non-Hispanic Black race, and depression symptoms were significantly associated with increased mental health services use during COVID-19. Thus, disparities based on race and financial status may have increased during COVID-19
Medical Marijuana Product Utilization Patterns and Preferences in the Treatment of Anxiety in Pennsylvania
No full textBackground: Medical Marijuana (MM) is a qualifying condition for the treatment of anxiety in Pennsylvania. This study analyzed MM products purchases and preferences at baseline and after 3 months, 6 months, 9 months, and 12 months after enrollment in the study for anti-anxiety treatment.
Methods: The observational study was composed of 116 subjects referred for MM use for anxiety and enrolled in a 12-month longitudinal study involving the treatment of MM with products containing Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and limonene. The percentage of THC, CBD, and limonene and routes of administration of these products were collected at baseline, 3 months, 6 months, 9 months, and 12 months mark. Product information was collected through the state seed-to-sale MM tracking system.
Results: Products purchased by participants contained average 27% THC, 3.28% CBD, and 0.73% limonene at baseline compared to 33.13% THC (significant increase, p ≤ 0.05), 1.64% CBD (significant decrease, p ≤ 0.05), and 0.88% (no significant change) limonene in the products used by them at 12 months. In terms of routes of administration of MM products purchased by patients were: 4.83% concentrates, 18.4% flower, 22.17% infused (e.g., capsules, tinctures, troches), 9.80% topical, 34.54% vape, and 10.26% used other products at baseline. The purchase (utilization) of MM products at 12 months were: 8.20% concentrate, 23.21% flower, 20.07% infused, 6.63% topical, 38.05% vape, and 3.84% used other MM products.
Conclusions: We observed an increase in the concentration of THC in cannabis products utilized by users compared to CBD and limonene from baseline to 12 months. Patients exhibited a higher preference for vape products as a route of administration compared to other MM products. This could be due to ease of use and immediate relief of anxiety by vape products among patients for anti-anxiety effects
Monotherapy Efficiency Compared to Combination Therapy for Treatment of Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia Targeting Pseudomonas aeruginosa
No full textIntroduction: Pseudomonas aeruginosa is a major cause of serious infections and contributes significantly to morbidity and mortality. This life-threatening pathogen is a common cause of pneumonia, and is resistant to multiple antibiotics. The 2016 Infectious Diseases Society of America recommends combination therapy for the treatment of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) combination caused by P.aeruginosa. Prior antibiotics use within 90 days, and high risk of mortality are risk factors for P.aeruginosa.
Objectives: This review aims to analyze literature that supports the use of combination therapy versus monotherapy for the empiric treatment of P. aeruginosa in HAP and VAP.
Methods: Online databases were used to find articles published pertaining to combination therapy versus monotherapy in the treatment of HAP and/or VAP. Databases used in online literature searches were Google Scholar using keywords Pseudomonas aeruginosa; monotherapy, Sciencedirect using keywords Pseudomonas aeruginosa; combination therapy; monotherapy, PubMed using keywords Pseudomonas aeruginosa; monotherapy;combination; pneumonia. Searches were selected if they met the following inclusion criteria: Study evaluate pseudomonas aeruginosa in pneumonia, HAP, VAP, mortality risk, comparing monotherapy and combination therapy in treatment of P. aeruginosa pneumonia. During the online search, studies were excluded if it pertained to bacteremia, cystic fibrosis, and/or community acquired pneumonia.
Results: Most of the observational studies included in this review found no significant difference in overall mortality between combination therapy and monotherapy, with mortality assessed at 14, 28, 30, and 90 days. Microbiological cure rates were also similar between the two approaches for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). Each study also included its own specific antibiotic regimens or interventions. It was noted that initiating appropriate antibiotic therapy is essential to reducing mortality. The monotherapy groups typically had more participants than the combination therapy groups. While the most recent studies are observational in nature, available randomized controlled trials are more than thirty years old. Retrospective and prospective studies remain the primary methods for comparing combination therapy and monotherapy, with randomized trials being infrequently conducted in this context.
Conclusion: Treating P. aeruginosa related pneumonia, whether hospital-acquired, ventilator-associated, or community-acquired, is complex. The evidence of combination therapy compared to monotherapy in treating P. aeruginosa pneumonia is limited. While current guidelines recommend combination therapy, the supporting evidence is weak. Future trials should focus on comparing the efficacy of combination therapy, monotherapy, and newer active agents for treating P.aeruginosa pneumonia
Spectrum of pathogens involved in eye infections observed at a rural hospital
No full textIntroduction: Infections of the eye and the surrounding structures may lead to serious complications including vision loss and death. In some cases, immediate intervention and aggressive treatment are necessary for preservation of vision. Globally, blindness and ocular morbidity continue to be a burden from bacterial infections with varying prevalence. In the United States, rates of antibiotic resistance continue to rise. The spectrum of pathogen involved in eye infections is quite diverse including bacteria and fungi. The cause of these infections varies regionally.
Objective: The primary objective of this study was to identify pathogens involved in eye and periorbital infections at a rural hospital in Maryland, USA.
Methods: Hospital database was searched for all patients presenting with infections of the eye which includes eyebrow, eyelid, and vitreous fluid during a 4-year period (September 2018 to December 2022).
Results: A total of 54 isolates from 44 patients (19 male/25 female) were identified. Nineteen percent were pediatric. Median BMI of the cohort was 29.1 (range 15.7-44.5) kg/m2. Of the specimens, 40 percent were labeled eye, 30 percent eyebrow/eyelid and 30 percent vitreous fluid. Thirty seven percent were sent by ophthalmologists with 36 percent from primary care physicians, 18 percent from ED, and 9 percent from other services. Abscesses and wounds accounted for 18 percent of specimens, 58 percent from fluid collections or tissue. Endophthalmitis was the most common clinical diagnosis (13 percent), and periorbital abscess and cellulitis accounted for 7 cases each. Microscopy of 41 specimens revealed WBC in 73 percent of specimens, Gram-positive cocci in 24 percent, Gram-negative rods 2 percent, and Yeast 2 percent. Staphylococci were cultured in 80 percent of the specimens, streptococci in 9 percent, enterococci in 2 percent, Gram-negative rods in 12 percent, anaerobes in 5 percent and Yeast in 2 percent (Candida dubliniensis). In one case, Neisseria gonorrhea was isolated. Staphylococcus aureus was the most common pathogen with 24 isolates of which 13 being Methicillin resistant. One patient had a mixed infection with Stenotrophomonas maltophilia and Achromobacter xylosoxidans
Conclusion: Consistent with prior studies, Staphalococcus aureus is a common cause of endophthalmitis and extra-vitreous infections. Knowledge of the spectrum of pathogens causing eye infections is crucial for choosing the correct antibiotics when initiating empiric therapy
Investigating the role of Crk-CrkL genetic deletions on exercise capacity in mice
No full textINTRODUCTION: Crk and CrkL genes encode intracellular adaptor proteins that play a role in development of the heart. Investigators have identified their developmental roles in the cardiac neural crest cells for cardiac outflow tract (OTF) septation by regulating apoptosis and smooth muscle differentiation. Mutations and deletions in Crk/CrkL have been linked to several human diseases, including congenital heart diseases that affect the OFT. We identified expression of both proteins in the myocardium, epicardium and epicardial-derived cells (EPDCs) that give rise to the coronary vascular cells and cardiac fibroblasts during embryonic mouse development. Previously, we determined that global deletion of Crk and CrkL in the mouse caused embryonic lethality at mid-gestation due to cardiac structural defects. Using a tissue-specific conditional deletion strategy, we generated mice with epicardial-specific deletions of Crk and CrkL. These Crk/CrkL epi+/- mice survived to adulthood and were subjected to physiological analysis.
OBJECTIVE: Our goal was to investigate the roles of Crk and CrkL in the mammalian heart by examining how they impact cardiovascular function and their potential consequences on systemic performance as demonstrated by exercise endurance.
METHODS: We generated mice with Wilms’ tumor 1-Cre-driven deletion of Crk and CrkL from the epicardium and EPDCs (Crk-CrkL epi+/-). This enabled us to bypass the embryonic lethality caused by global deletion of Crk-CrkL in mice. As a result, we obtained mice with 2-, 3- and 4-allele conditional epicardial deletions of Crk and CrkL. Our lab made physiological comparisons between Crk-CrkL epi+/- mice and Crk-CrkL control mice. Exercise tolerance studies were conducted on 13–14 week old control and Crk-CrkL epi+/- mice by exercising them on a rodent treadmill under fatiguing conditions. We determined their capacity for exercise endurance by measuring the total run distance and total run time of these mice. These values were compared between control and Crk-CrkL epi+/- mice.
RESULTS: Our data indicated that Crk-CrkL epi+/- mice achieved a greater total running distance and a longer period of running time than control mice. Thus, these mice had a higher capacity of exercise endurance than control mice under fatiguing conditions.
CONCLUSION: These results indicate that epicardial-specific deletion of Crk and CrkL enhances exercise endurance in adult mice. We speculate this increase may be related to adaptations of the cardiovascular system to enhance blood flow and delivery to the systemic circulation to support the increased tissue demands at the local level. Future studies will be performed to identify the mechanisms underlying these cardiovascular adaptations
Chronic intranasal xylazine use resulting in nasal, palatal, and orbital floor necrosis with inferior rectus entrapment
Full text linkXylazine, a non-opioid veterinary tranquilizer not approved for human use, has infiltrated the illicit drug supply causing public health officials to release statements warning of an emerging epidemic. Referred to as “Tranq” or “Tranq-Dope” when combined with heroin or fentanyl, recreational xylazine in the United States was first detected in Philadelphia in 2006, and has been associated with increasing fatal overdoses and chronic necrotic wounds. Xylazine functions as a strong synthetic alpha-2-adrenergic agonist but is thought to have partial alpha-1-adrenergic agonist activity, inducing peripheral vasoconstriction, poor perfusion, and necrosis. Numerous case reports and media photos have emerged of “characteristic necrotic skin ulcers” resulting from xylazine injection. However, little has been reported on the physical consequences of intranasal Xylazine usage. To our best knowledge, we present the first case that highlights complications of intranasal xylazine inhalation as well as the first report of inferior rectus entrapment resulting from intranasal drug usage
Recurrence of symptoms following conservative and surgical treatment for lumbar radiculopathy: A literature review
Full text linkIntroduction: Lumbar radiculopathy is a common clinical problem and remains a controversial diagnosis at fundamental levels, including its diagnostic criteria, pathophysiology, and optimal treatment. Patients with lumbar radiculopathy may improve with either conservative or surgical treatment; the specific treatment chosen is based on patient preferences, priorities of care, and comorbidities. However, there is limited evidence from clinical studies to support treatment choice in daily practice. The purpose of this literature review is to summarize evidence regarding the recurrence of symptoms following conservative treatments and surgical treatments for patients with lumbar radiculopathy.
Methods: The review was conducted using the OneSearch database with a specific emphasis on finding potential predictors of recurrence of pain, including time to symptom resolution, sociodemographics, work-related factors, and baseline pain levels.
Results: Studies reveal varying rates and patterns of symptom recurrence among patients treated with medical interventions. Conservative treatments, including physical therapy and pharmacological approaches, demonstrated mixed outcomes in terms of symptom recurrence. Conservative treatment is usually considered appropriate for patients without clear anatomic abnormalities. While some patients experienced sustained relief, others faced recurrent symptoms over time, influenced by factors such as treatment duration and adherence. Surgical treatments result in long-term improvement, with sensory deficits improving first, followed by pain and motor function. Although surgical outcomes are promising, the rates of surgical complications may require reoperation due to failure of surgery to resolve symptoms or failure of pain cessation altogether, making medical management necessary.
Conclusions: There are no prospective controlled studies to guide physicians in the comprehensive management of patients with recurrence of symptoms from medical and surgical treatments for lumbar radiculopathy, although a few randomized controlled trials address these modalities in the symptomatic treatment of back pain. A standardized approach based on collaboration among a primary care physician, back surgeon, physical therapist, psychiatrist, and, if required, a pain management specialist would be the best course of action in the management of these patients