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Post-radiation Angiosarcoma of the Vagina: A Case Report and Literature Review
No full textBackground: Angiosarcomas are aggressive and rare mesenchymal neoplasms commonly presenting on the skin. Angiosarcomas are known to occur secondary to radiation; however, the majority of these cases occur in the breast, skin, and soft tissues. In the past 30 years, although the incidence of angiosarcoma has risen for incompletely understood reasons, angiosarcomas of gynecologic origin remain very rare. To our knowledge, there have only been 10 cases of angiosarcoma of the vagina or vulva secondary to radiation. Of those cases previously reported, the prognosis has been dismal. The median survival period for angiosarcomas secondary to irradiation has been reported as 12 months. We believe this may be the first documented case of post-radiation vaginal angiosarcoma with complete remission. Case Presentation: An 83-year-old female patient with a history of robotic-assisted hysterectomy was diagnosed with rectal carcinoma in 2006. The rectal carcinoma was then removed via low anterior resection, and subsequent examination showed involvement of one lymph node. The patient then underwent radiation therapy and adjuvant chemotherapy to treat regional involvement. In 2010, four years later, the patient was found to have solitary pulmonary metastasis. This was treated with surgical resection. After 10 years, in 2020, the patient presented for vaginal bleeding. Imaging performed in 2010, at the time of pulmonary metastasis, showed no gynecologic involvement (Figure 1A, 1B). However, a repeat computed tomography (CT) scan without contrast done in 2020 following episodes of vaginal bleeding showed a 4 cm mass at the vaginal cuff (Figure 2A, 2B). A biopsy of the vaginal mass was conducted and demonstrated high-grade angiosarcoma, believed to be secondary to radiation therapy. As the patient was not a surgical candidate, angiosarcoma was treated with Taxol chemotherapy. Despite the poor prognosis associated with angiosarcoma, the patient exhibited a significant response to treatment. Follow-up magnetic resonance imaging (MRI) performed in July 2021, September 2021, and December 2021 showed a complete response to treatment. The patient has not had a recurrence of angiosarcoma since. Conclusions: Angiosarcomas are rare mesenchymal neoplasms; however, they should always be on your differential in a previously irradiated area, for they may mimic the recurrence of the initial tumor. The mean time period for post-radiation angiosarcoma to appear is around 6-7 years, and this case shows the importance of recognizing that occurrence outside of the mean should not be overlooked. Furthermore, this case may help revolutionize and standardize the treatment for post-radiation angiosarcomas due to the complete remission found with Taxol therapy in our patient, which has been documented to have the most success in the limited literature on this topic
Efficacy of Using Zoledronate for Prevention of Craniofacial Fractures in Mice with Osteogenesis Imperfecta
No full textOsteogenesis imperfecta (OI) is a genetic disorder of type I collagen that results in increased bone fragility, increased fracture rates, and abnormalities of the limbs, vertebral column, and craniofacial skeleton. Long-lasting bisphosphonate drugs, like zoledronate, are used in children with OI to increase bone mineral density and prevent skeletal fractures. Zoledronate increases osteoclast apoptosis, thus reducing relative rates of bone resorption and increasing formation rates. Previous experimental research on the efficacy of zoledronate has focused largely on the postcranial skeleton (e.g. limbs). The goal of this study is to investigate if zoledronate reduces the rate of craniofacial fractures in mice with osteogenesis imperfecta. We hypothesize that mice treated with zoledronate will have fewer skeletal fractures of the skull compared to untreated mice. Mice with OI (OIM, B6C3Fe a/a-Col1a2^oim/oim) and unaffected littermates (wild-type, WT) were randomly assigned into either control (C) or zoledronate (ZOL) treatment groups (n=10-12/genotype/group). Mice treated with zoledronate received subcutaneous injections of the drug (80 µg/kg) at 4, 8, and 12 weeks of age. The craniofacial skeleton of all mice was imaged with a micro-CT scanner (20 µm³ voxels) every 4 weeks from 4-16 weeks. 3D models of the craniofacial skeleton were generated in 3D Slicer software and analyzed for incidence and location of fractures. No craniofacial fractures were observed in WT mice, regardless of treatment, at any timepoint. At 4 weeks, prior to the first administration of ZOL, 80% of all OIM mice had skeletal fractures. While the rate of fracture in OIM-C mice steadily rose to 100% by week 16, the rate of fracture in OIM-ZOL mice decreased to 70% at weeks 8/12 and 60% by week 16. Furthermore, OIM-ZOL mice showed increased signs of fracture healing by week 16 (40%) compared to OIM-C mice (11%). Skeletal fractures in OIM mic were most commonly observed along the zygomatic arch, proximal to the masseter muscle. These fractures were both bilateral and unilateral. Preliminary data indicates that treatment with zoledronate starting at 4 weeks of age reduces the incidence of craniofacial fractures in mice with OI, as well as increases the rate of healing in fractures that do occur. The high rate of fracture observed the beginning of this study suggests the need for earlier interventions, prior to weaning. Additionally, the prevalence of fractures proximal to skeletal attachment sites for feeding muscles suggestions that muscle-bone interactions are a key component for understanding the origin of facial fractures in this model. Previous work has shown that long-term use of bisphosphonates like zoledronate may have negative outcomes for the craniofacial skeleton, including delayed bone formation, altered dental eruption, and osteonecrosis of the jaw (ONJ). This study suggests that craniofacial health is an important consideration, distinct from postcranial health, when planning interventions for patients with OI
Proteomic Analysis Evaluating the Cellular and Functional Processes of Mithramycin and Etoposide Combination Treatment in Ewing Sarcoma Cells
No full textPurpose: Ewing Sarcoma (ES) is an aggressive malignant cancer that targets bones and connective tissue in both adults and adolescents. Because of its ability to metastasize to other parts of the body, it has a poor survival rate. To increase the survival rate, it is important to continuously research new and improved treatments. EWS-FLI1, a fusion protein produced by 85% of ES tumors, has emerged as a promising new target for drug therapy. Mithramycin is one drug that has shown promise as it is known to inhibit EWS-FLI1. This study serves to investigate how Mithramycin and Etoposide combination treatment is effective in inhibiting cell function and cell growth. Future studies will advance treatments by utilizing the proteomic data presented here. Methods: ES cells were obtained from a commercial source. Line TC205 was cultured and treated with increasing concentrations of Mithramycin or Etoposide or combination of both. Cell viability was measured using a luminescence-based assay, and IC₅₀ values were determined using Graphpad Prism Software. Proteomic analysis was conducted on triplicate cell pellets using MaxQuat and LFQAnalyst to identify changes in protein expression following treatments. Results: Both Mithramycin and Etoposide were able to reduce TC205 on their own. When used in combination, they demonstrated a synergistic effect by significantly decreasing cell viability. Further proteomic analysis showed that cellular and functional processes in the cancer cells were impacted by the combination treatment. Conclusion: The combination of Mithramycin and Etoposide was more effective against TC205 cell lines than monotherapy with either drug alone. Proteomics findings identified other proteins and pathways that the treatment altered. This data will help us to comprehend the mechanisms underlying Mithramycin and Etoposide treatment to develop new approaches for treating Ewing Sarcoma in patients
Investigating the Relationship Between Humeral Morphology and Observational Frequencies of Locomotor and Substrate Activity in Anthropoid Primates
No full textShoulder morphology differs greatly in primates, balancing a need for flexibility and stability in locomotion; and is widely incorporated into studies of locomotor behaviors in living and extinct primates. However, few studies incorporate locomotor frequency values from observational studies, limiting our understanding of morphological and functional links. This study investigates the relationship between humeral shape and quantitative frequencies of locomotion and substrate use in extant primates to provide a better understanding of humerus shape and function in extant and fossil primates. Frequencies of locomotor behaviors (% quadrupedalism, suspension, climbing, leaping, bipedalism) and substrate use (arboreal, semi-terrestrial, terrestrial) were taken from the literature for six platyrrhines, five cercopithecoids, and four hominoids. Shoulder morphology was studied with standard geometric morphometrics, with landmarks on proximal and distal humeral traits. Univariate phylogenetic generalized least squares regressions were run to identify covariance of humeral shape to locomotion, and substrate use in each group. For all humeral traits, phylogenetic signal was statistically significant (K=0.5-0.64; p=0.001-0.024). In cercopithecoids, both tubercles, olecranon fossa and both epicondyles significantly covaried with substrate use (R²=0.534-0.8) and % quadrupedalism, climbing and leaping (R²=0.63-0.85). Notably, the medial epicondyle and greater tubercle had the largest R² values when covarying with substrate use (R²=0.8) and locomotion (R²=0.85), respectively. Hominoids showed significant covariance of the humeral head, greater tubercle and olecranon fossa and substrate use (R²=0.32-0.49). Overall, hominoids had greater covariance with the humeral head, both tubercles, olecranon fossa, capitulum and lateral epicondyle and all locomotor behaviors (R²=0.45-0.71). In platyrrhines, only the olecranon fossa significantly covaried with substrate use (R²=0.216), with the lateral epicondyle also covarying with % quadrupedalism, suspension, climbing and leaping (R²=0.388-0.641). The results suggest frequency data from observational studies can be used successfully to reflect more accurate relationships between humeral morphology and behavior. Significant covariance between the greater tubercle and locomotion, and medial epicondyle and substrate use in cercopithecoids supports previous research suggesting that these features are especially relevant in determining catarrhine behavior. Greater covariance of hominoid locomotor behavior is notable as larger-bodied apes have high locomotor diversity, yet specific patterns can be identified. Future work will apply the findings to Miocene fossils to better characterize locomotor and substrate diversity of early catarrhines
Recruitment and engagement of a cohort of women living with HIV in Nigeria: Baseline characteristics from the Nigeria Implementation Science Alliance
Full text linkNigeria has a high burden of mother to child transmission (MTCT) of HIV. There is paucity of large-scale prospective cohort studies to provide insight into the reasons for the abysmal MTCT indices. This paper describes the baseline characteristics of women living with HIV who signed consent to participate in future clinical or implementation trials. The Nigeria Implementation Science Alliance (NISA) developed an open multicentre prospective cohort of women of reproductive age living with HIV, drawn from 12 facilities across the six geo-political regions of Nigeria. Research Electronic Data Capture system was used for the informed consent process. Socio-demographic and clinical information of participants were accessed through the clinics' Electronic Medical Records. We calculated descriptive statistics, summarizing categorical variables using frequencies and percentages. Numerical variables were summarized using means and standard deviations for normally distributed, and median and interquartile ranges for skewed variables. We recruited 18,210 women living with HIV. Eighty-one percent (14,777/18,210) had their data extracted from the EMR. Data of 10,996 women were analysed. The mean age was 37.4 +/- 7.2 years, with 85% in age groups >/=30-39 years. The median time since HIV diagnosis was 8 years (IQR 3-11 years) while the median length of time on ART was 6 years (IQR 3-10 years). For women who had a record of WHO clinical staging and most current viral load, majority (80%) were in WHO stage 1 while two thirds (68.0%) had viral load of <20 copies/mm3. Almost all women (94%) were on first-line antiretrovirals, with none on the third-line regimen. This unique cohort in Nigeria that will provide researchers with a platform to propose and answer several research questions about the health of women and infants providing policymakers with information on maternal and child health in Nigeria.This work was supported in part by funding from the Nigeria Implementation Science Alliance (EEE), IVAN Research Institute (EEE), and Healthy Sunrise Foundation (EEE). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Long COVID Is Associated with Excess Direct Healthcare Expenditures Among Adults in the United States
No full textBackground: Long COVID can lead to a considerable economic burden because of ongoing care for persistent symptoms such as fatigue, dyspnea, or cognitive dysfunction. However, systematic research quantifying healthcare expenditures associated with long COVID remains limited. Objective: This study estimated the excess total, payer, and out-of-pocket healthcare expenditures associated with long COVID among adults in the United States (US). Methods: This was a cross-sectional analysis on adults >/=18 years using 2022 Medical Expenditure Panel Survey (MEPS) data (N = 17,119; representing approximately 254 million adults). Economic burden was measured with (1) total, (2) payer, and (3) out-of-pocket expenditures by individuals and their families. Generalized linear models (GLMs) with gamma distribution and log link were utilized to estimate excess expenditures associated with long COVID after adjusting for age, sex, race and ethnicity, social determinants of health, health status, and lifestyle factors. Results: Overall, 7.0% of the population reported long COVID. Adults with long COVID exhibited higher total (USD 11,305 vs. USD 7162) and payer (USD 9983 vs. USD 6097) expenditures compared to those with no COVID. In a fully adjusted analysis, long COVID was associated with an excess of USD 4098 in total healthcare expenditures and USD 3705 in payer expenditures. We did not observe significant differences in out-of-pocket expenditures between those with long COVID and no COVID. Conclusions: Adults with long COVID had 1.5 times higher total healthcare costs compared to those without COVID. This study highlights the need for comprehensive strategies and policies to reduce the economic burden associated with long COVID.This research received no external funding
Empagliflozin alters cardiac output of males in a dahl salt sensitive model of heart failure.
No full textPurpose: Empagliflozin is a sodium glucose co-transporter inhibitor (SGLT2i) originally used to treat diabetes. Recently, empagliflozin has been shown to reduce hospitalizations and reduce mortality in patients with heart failure with preserved ejection fraction (HFpEF). However, the mechanism of action of how empagliflozin improves clinical outcomes in HFpEF is yet to be determined. We hypothesize that empagliflozin will help improve heart function by improving cardiac measures. Methods: To develop our heart failure model, Dahl salt sensitive rats (n=12) who are prone to become hypertensive when fed a high salt diet and eventually develop heart failure were chosen for this study. These rats were then randomly assigned into one of our three groups: control, high salt (HS), high salt + empagliflozin (HS+Empa) and fed their respective diet for 8 weeks. Both the HS group and HS + Empa group were fed a high salt diet (8% NaCl) and at the same time, the HS + Empa group had Empagliflozin administered in their water at a dose of 10 mg/kg/day. During these 8 weeks, the rats were put to exercise to evaluate exercise tolerance and also examined for weekly echocardiography measurements that were used to assess cardiac output, ejection fraction, diastolic function and other key cardiac parameters. As part of our study, we also incorporated histological techniques that will give us information about the cardiac’s tissue such as myocardial fibrosis, cardiac muscle hypertrophy, and any excess collagen deposition. Results: Based on our current and preliminary data, empagliflozin has had a minimal effect on hemodynamics parameters of the heart. Cardiac output levels have remained roughly the same for all three groups with cardiac output ranging from 0.17-0.24 l/min. Our ejection fraction measurements also indicated minimal differences as our control group had 88% EF and our HS & HS+EMPA both had 86% EF. For the most part, we noticed no changes in sex differences when analyzing the ejection fraction but did observe a difference in empagliflozin’s effect on the male’s cardiac output. After 8 weeks, there was a significant decrease in the cardiac output of our HS+ Empa group (0.16 l/min) compared to the control group (0.27 l/min) and the HS group (0.28 l/min). Conclusion: We can tentatively see a preserved ejection fraction, maintained exercise performance, and a decreased cardiac output for the males. When taking a closer look at the 2 factors that contribute to cardiac output (heart rate & stroke volume), combined with our results we could infer that this decrease in cardiac output combined with the ability of our treatment group to maintain exercise performance compared to our control could be due to a lower heart rate. As we keep on collecting and analyzing data, our main objective is to determine if there is indeed a significant difference in our echocardiography parameters and also if our histological data can support these results, eventually leading to a further understanding on empagliflozin’s mechanism of action
A curious case of biopsy negative Microscopic Polyangiitis
No full textMicroscopic Polyangiitis is an ANCA associated necrotizing vasculitis of small vessels at an average age of onset between 50 to 70 years affecting the lungs, kidneys and other organs affecting just 1.5 persons per 100,000 per year in the US. It differs from the other 2 types of small vessel vasculitis; Granulomatosis with Polyangiitis (GPA) and Eosinophilic Granulomatosis with Polyangiitis (EGPA) based on a few key features and serologic differences. This is a case of a 73 yo female patient who presents with an incidental finding of decreased kidney function (Cr 3.7) following a femur fracture and a 48-hour history of long lie. Over the course of the next few months, she presented with multiple episodes of scant hemoptysis with pneumonia and worsening CKD ultimately necessitating dialysis (Cr 8.71) for ESRD. Chest CT demonstrated diffuse patchy ground glass alveolar opacities bilaterally. Bronchoscopy and bronchioalveolar lavage revealed diffuse alveolar hemorrhage with microscopic scant respiratory mucosal elements and alveolar macrophages with background histiocytes. Serology was positive for significant titers of p-ANCA myeloperoxidase autoantibodies. Renal biopsy showed advanced chronic changes described as collapsing glomerulonephropathy with focal segmental and diffuse global glomerulosclerosis and no evidence of immune complex mediated glomerulonephritis with severe interstitial fibrosis (70-80%) and arteriosclerosis. In this case the absence of necrotizing pauci-immune vasculitis of small vessels or pauci-immune (acute) necrotizing crescentic glomerulonephritis makes this a curious case as they typically seen in 80 to 100% of renal biopsies of patients with MPA. Patient has currently been initiated on Rituximab as it is a key treatment option for microscopic polyangiitis (MPA), particularly in patients with severe or refractory disease. It is effective in inducing remission and preventing relapses, with the advantage of fewer long-term side effects compared to cyclophosphamide. Therapeutic intervention may mitigate the progression of concurrent interstitial lung disease (ILD)-associated respiratory failure. Continuation of tailored immunosuppression aimed to attenuate pulmonary inflammation, potentially stabilizing respiratory function. This case underscores the importance of balancing risks and benefits in multisystem vasculitis management
Low Grade Appendiceal Mucinous Neoplasm With Metastasis To Right Ovary (Krukenberg Tumor with Pseudomyxomatous Peritonei)
No full textBackground: Low-grade appendiceal mucinous neoplasms (LAMN) are characterized by adenomatous changes in the appendiceal mucosa with features of indeterminate malignancy, and are primarily described as “mucinous cystadenomas”. LAMNs are associated with conditions such as mucoceles, pseudomyxoma peritonei syndrome (PMP), and ovarian involvement that can result in Krukenberg tumors. Case: A 49-year-old female presented with acute abdominal pain, prompting an order for a CT scan of the abdomen/pelvis. The scan revealed a large pelvic cystic mass extending from the pelvis into the abdomen, causing displacement of the bowel. This mass, measuring 19.3cm x 20cm x 14cm, was located above the bladder and distinct from the uterus. A smaller cystic structure adjacent to the larger mass on the right was identified, later found to be continuous with the appendix above. Mild ascites, evidenced by perihepatic fluid in the right upper quadrant, was noted. Initially, the primary differential diagnosis was a serous/mucinous cystadenoma/cystadenocarcinoma. A subsequent MRI of the abdomen confirmed the CT findings and revealed internal thin peripheral septations within the lesion. During surgery, an appendiceal mucocele was discovered, with a pathologic diagnosis of a LAMN with right ovary metastasis, forming a predominant Krukenberg mucinous cystic mass. The ascites was determined to represent pseudomyxoma peritonei (PMP). Conclusion: Identifying low-grade appendiceal mucinous neoplasms (LAMN) can pose a diagnostic challenge, as their clinical presentation can overlap with ovarian mucinous neoplasms and other abdominal primary tumors. The misdiagnosis of a metastatic ovarian tumor from a krukenberg tumor secondary to a LAMN can result in extraneous surgical interventions and increased risk of iatrogenic morbidity. Here we present a rare case of a patient with a LAMN with metastasis to the right ovary, who was thought to present with an ovarian cystadenoma/cystadenocarcinoma until MRI/CT findings were utilized to diagnose a LAMN. This case serves as an example of the importance of CT and MRI when differentiating LAMN with Krukenberg tumors and PMP from primary ovarian tumors. They can also be utilized to guide and predict surgical outcomes, thereby reducing the risk of unnecessary interventions and iatrogenic morbidity
Comparative Analysis of State Training and Implementation Resources for Unassigned Albuterol
No full textPurpose: The CDC estimates that nearly 10% of school-aged children have current asthma and about half of these cases are inadequately managed despite medical advances that allow the majority of asthma cases to be readily controlled. Poor management is associated with adverse outcomes including increased school absenteeism, sleep disruptions, reduced engagement and readiness to learn during the school day, and potentially preventable emergency service use, hospitalizations, and mortality. The result is elevated risk at the intersection of health and education. Current best practice is for children with asthma to have access to quick-relief (albuterol) medication at all times including the school-day, in case of asthma exacerbations, Unfortunately, only about 15% of students do. One solution is for school campuses to keep “stocks” of albuterol. Despite large numbers of asthmatic children, few states have legislature and administrative code pertaining to keeping extra, or “stock albuterol” rescue inhalers on campuses. The objective of this project is: 1) To evaluate which states have legislature and administrative code regarding stock albuterol, 2) Evaluate the quality of each state’s legislature and administrative code as it compares to recommended implementations detailed in current literature, and 3) Focus on training of personnel that are allowed to administer stock albuterol on campuses. Methods: The Westlaw legal database and official government state websites were used to identify legislation, regulation, training modules, and other implementation tools related to stock albuterol. Key words were established based on existing literature, legislative sources, and consultation with a research librarian. A data extraction tool was developed by analyzing national guidelines for unassigned albuterol and creating a binary variable for each element of recommended best practice. All pertinent state policy, regulation and implementation guidelines were independently reviewed by two student researchers and analyzed to determine whether content aligned or did not align with each best practice variable was met or not met. Content was coded accordingly. Results: Twenty-three states have been identified via Westlaw legal database and official government state websites that have legislation pertinent to stock albuterol administration. Of the states analyzed, 56.5% had standardized stock albuterol training, 56.5% detailed where stock albuterol could be administered, 87.0% included recognizing signs of respiratory distress, and 65.2% required renewal of training. Conclusions: The training parameter of stock albuterol administration emerged as the most poorly characterized element of best practice in existing policy, regulation, and code. Training requirements and content also reveal large variability and lower alignment with best practice in comparison to elements. Results can also provide guidelines for states working to adopt or implement stock albuterol policy, revise existing policy or regulation, or develop implementation and training tools. Establishing a national repository of policy, regulatory, and implementation tools for stock albuterol would allow for tracking of national trends, support best practice implementation, and provide a critical tool to investigate the use of stock albuterol to improve asthma outcomes for students in diverse implementation settings across the United States