Geographic Disparities and Payment Variation for Immediate Lymphatic Reconstruction in Massachusetts.

BACKGROUND: Little is known about practice patterns and payments for immediate lymphatic reconstruction (ILR). This study aims to evaluate trends in ILR delivery and billing practices. METHODS: We queried the Massachusetts All-Payer Claims Database between 2016 and 2020 for patients who underwent lumpectomy or mastectomy with axillary lymph node dissection for oncologic indications. We further identified patients who underwent lymphovenous bypass on the same date as tumor resection. We used ZIP code data to analyze the geographic distribution of ILR procedures and calculated physician payments for these procedures, adjusting for inflation. We used multivariable logistic regression to identify variables, which predicted receipt of ILR. RESULTS: In total, 2862 patients underwent axillary lymph node dissection over the study period. Of these, 53 patients underwent ILR. Patients who underwent ILR were younger (55.1 vs 59.3 years, P = 0.023). There were no significant differences in obesity, diabetes, or smoking history between the two groups. A greater percentage of patients who underwent ILR had radiation (83% vs 67%, P = 0.027). In multivariable regression, patients residing in a county neighboring Boston had 3.32-fold higher odds of undergoing ILR (95% confidence interval: 1.76-6.25; P < 0.001), while obesity, radiation therapy, and taxane-based chemotherapy were not significant predictors. Payments for ILR varied widely. CONCLUSIONS: In Massachusetts, patients were more likely to undergo ILR if they resided near Boston. Thus, many patients with the highest known risk for breast cancer-related lymphedema may face barriers accessing ILR. Greater awareness about referring high-risk patients to plastic surgeons is needed.

Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The renal sympathetic nervous system modulates systemic blood pressure, cardiac performance, and renal function. Pathological increases in renal sympathetic nerve activity contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). We investigated the effects of renal sympathetic denervation performed at early or late stages of HFpEF progression. METHODS AND RESULTS: Male ZSF1 obese rats were subjected to radiofrequency renal denervation (RF-RDN) or sham procedure at either 8 weeks or 20 weeks of age and assessed for cardiovascular function, exercise capacity, and cardiorenal fibrosis. Renal norepinephrine and renal nerve tyrosine hydroxylase staining were performed to quantify denervation following RF-RDN. In addition, renal injury, oxidative stress, inflammation, and profibrotic biomarkers were evaluated to determine pathways associated with RDN. RF-RDN significantly reduced renal norepinephrine and tyrosine hydroxylase content in both study cohorts. RF-RDN therapy performed at 8 weeks of age attenuated cardiac dysfunction, reduced cardiorenal fibrosis, and improved endothelial-dependent vascular reactivity. These improvements were associated with reductions in renal injury markers, expression of renal NLR family pyrin domain containing 3/interleukin 1ß, and expression of profibrotic mediators. RF-RDN failed to exert beneficial effects when administered in the 20-week-old HFpEF cohort. CONCLUSIONS: Our data demonstrate that early RF-RDN therapy protects against HFpEF disease progression in part due to the attenuation of renal fibrosis and inflammation. In contrast, the renoprotective and left ventricular functional improvements were lost when RF-RDN was performed in later HFpEF progression. These results suggest that RDN may be a viable treatment option for HFpEF during the early stages of this systemic inflammatory disease.

Identification of potent anticancer copper(ii) complexes containing tripodal bis[2-ethyl-di(3,5-dialkyl-1H-pyrazol-1-yl)]amine moiety.

A series of heteroleptic copper(ii) complexes of the composition [Cu(L1-5)Cl]X, where X = ClO4 and/or PF6 and [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl))-(6-methyl-(2-pyridylmethyl))]amine (L1), [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl))-(3,4-dimethoxy-(2-pyridylmethyl))]amine (L2), [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl)-(2-quinolymethyl)]amine (L3), [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazolyl)-(di(3,5-dimethyl-1H-pyrazol-1-yl-methyl))]amine (L4) and [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl)-(5-methyl-3-phenyl-1H-pyrazol-1-yl-methyl)]amine (L5), were prepared and thoroughly characterized including single-crystal X-ray diffraction technique. The in vitro cytotoxicity of complexes against A2780, A2780R, HOS and MCF-7 human cancer cell lines was evaluated using the MTT test. The results revealed that complexes [Cu(L1)Cl]PF6 (1-PF6), [Cu(L2)Cl]ClO4 (2-ClO4) and [Cu(L3)Cl]PF6 (3-PF6) are the most effective, with IC50 values ranging from 1.4 to 6.3 µM, thus exceeding the cytotoxic potential of metallodrug cisplatin (IC50 values ranging from 29.9 to 82.0 µM). The complexes [Cu(L4)Cl]PF6 (4-PF6) and [Cu(L5)Cl]PF6 (5-PF6) showed only moderate cytotoxicity against A2780, with IC50 = 53.6 µM, and 33.8 µM, respectively. The cell cycle profile, time-resolved cellular uptake, interactions with small sulfur-containing biomolecules (cysteine and glutathione), intracellular ROS production, induction of apoptosis and activation of caspases 3/7 were also evaluated in the case of the selected complexes. It has been found that the best performing complexes 1 and 2 cause cell arrest in the G2/M phase and induce apoptosis via the increase in production of ROS, dominantly due to the overproduction of superoxide.

Longest reported case of symptomatic COVID-19 reporting positive for over 230 days in an immunocompromised patient in the United States.

Coronavirus 2019 (COVID-19) pneumonia was first noted in Wuhan, China. Since the start of the pandemic, there have been millions of cases diagnosed. The average time from onset of symptoms to testing negative SARS-CoV-2 via reverse transcription polymerase chain reaction is roughly 25 days. In patients who continually test positive for COVID-19, it is essential to determine precisely which risk factors contribute to the increase in viral shedding duration. We present a case about a 62-year-old man who has persistently tested positive for COVID-19 for more than 230 days. We followed his treatment course, in which he had been hospitalized multiple times since the onset of symptoms back in April 2020. We have determined that patients with immunosuppression, especially those taking corticosteroids, are at increased risk of prolonged viral shedding. It is essential to continually monitor these immunocompromised patients as they required a greater time period in order to have an appropriate immune response in which antibodies are created.

Post COVID-19 MSSA pneumonia.

Coronavirus disease 2019 (COVID-19) was first identified at the end of 2019 as a cluster of pneumonia cases in Wuhan, China. By February 2020, this virus quickly spread, becoming a global pandemic. The spectrum of symptomatic infection severity can range from mild, severe, and critical disease. Many correlated comorbidities were established, including smoking, socioeconomic background, gender (male prevalence), hypertension, obesity, cardiovascular disease, chronic lung disease, diabetes mellitus, cancer, and chronic kidney disease. In an extensive literature search, post-COVID-19 necrotizing Staphylococcus aureus pneumonia with pneumothorax has not been recorded. We present a case about a 62-year-old male who presented with symptoms of COVID-19 with many underlying comorbidities, including hypertension and hyperlipidemia. He was on ventilatory support during his first week in the hospital and then received supplemental oxygenation as he recovered from his COVID-19 pneumonia. Nearly a month and a half after his initial presentation, he quickly decompensated and was started on supplemental oxygen and the necessary treatments. It was then, with the aid of lab work and imaging, that we determined that he had developed necrotizing Staphylococcus aureus pneumonia with pneumothorax. He was adequately treated, and once he was stable, he was discharged home and was told to continue his therapy.

Salivary anti-SARS-CoV-2 IgA as an accessible biomarker of mucosal immunity against COVID-19.

Background: Mucosal immunity, including secretory IgA (sIgA), plays an important role in early defenses against respiratory pathogens. Salivary testing, the most convenient way to measure sIgA, has been used to characterize mucosal immune responses to many viral infections including SARS, MERS, influenza, HIV, and RSV. However, its role has not yet been characterized in the COVID-19 pandemic. Here, we report development and validation of a rapid immunoassay for measuring salivary IgA against the SARS-CoV-2 virus, and report quantitative results in both pre-COVID-19 and muco-converted subjects. Methods: We developed and refined a specific test for salivary IgA against SARS-CoV-2 on the Brevitest platform, a rapid immunoassay system designed for point-of-care use. A qualitative test was validated as per FDA guidelines with saliva obtained from subjects prior to the emergence of COVID-19, and from PCR-confirmed COVID-19 patients. We also generated a quantitative measure of anti-SARS-CoV-2 salivary IgA. Time taken for saliva self-collection was measured and its ease-of-use assessed. Results: We successfully validated a qualitative salivary assay for SARS-CoV-2 IgA antibodies, with positive and negative predictive values of 92% and 97%, respectively, and no observable cross-reactivity with any of seven potential confounders. Pre-COVID-19 saliva samples showed an 8-fold range of IgA concentrations, suggesting a broad continuum of natural antibody resistance against the novel virus, though at levels lower than that observed in COVID-19 PCR-confirmed subjects. Samples from muco-positive subjects also shown a ~9-fold variation in salivary IgA levels, with elevated salivary IgA observed beyond three months after onset of symptoms. We observed a correlation (r=0.4405) between salivary IgA levels and COVID-19 disease severity. In anecdotal observations, we observed individuals who exhibited antibodies early in the course of their disease, contemporaneously with a positive PCR test, as well as individuals who muco-converted despite no known direct exposure to a COVID-19 patient, no symptoms, and negative molecular and/or serum antibody tests. Salivary collection took 5-10 minutes, and was reported as being easy (mean of 1.1 on a scale of 1 to 10). Implications: Mucosal immunity, including secretory IgA, plays an important role in host defense against respiratory pathogens, and our early data suggest it may do so in COVID-19. Salivary IgA, an accessible marker of mucosal immunity, may be a useful indicator of several key parameters including individual and community immune response, disease severity, clinical risk, and herd immunity. The non-invasive nature and ease of saliva collection facilitates its potential use as a biomarker for ongoing patient assessment and management, as well as a community surveillance tool. By measuring mucosal immune responses directly and systemic immune responses indirectly, salivary IgA could be useful in developing and deploying a vaccine(s) against COVID-19. Quantitative IgA assessment could also potentially serve as a tool to segment the population into different risk categories and inform individual and collective decisions relating to appropriate activities and vaccine prioritization/delivery. These data reinforce the importance of further investigation into the role of mucosal immunity and IgA in host responses against COVID-19.

Identifying the Most Common CrossFit Injuries in a Variety of Athletes.

BACKGROUND: CrossFit is an increasingly popular, rapidly growing exercise regimen. Few studies have evaluated CrossFit-associated musculoskeletal injuries on a large scale. This study explores such injuries and associated risk factors in detail. OBJECTIVE: To identify the most common musculoskeletal injuries endured during CrossFit training among athletes at different levels of expertise. DESIGN: Survey-based retrospective cross-sectional study. SETTING: Distribution at CrossFit gyms in the United States and internationally. Also published on active online forums. PARTICIPANTS: A total of 885 former and current CrossFit athletes. METHODS: Institutional review board-approved 33-question Web-based survey focused on CrossFit injuries and associated risk factors. Survey submissions were accepted for a period of 6 months. MAIN OUTCOME MEASUREMENTS: Specific injuries with associated workouts, risk factors that affected injury including (1) basic demographics, (2) regional differences in reported injuries, (3) training intensity, and (4) expertise level at time of injury. RESULTS: Of the 885 respondents, 295 (33.3%) were injured. The most common injuries involved the back (95/295, 32.2%) and shoulder (61/295, 20.7%). The most common exercises that caused injury were squats (65/295, 22.0%) and deadlifts (53/295, 18.0%). Advanced-level (64/295, 21.7%) athletes were more significantly injured than beginner-level (40/295, 13.6%) athletes. International participants were 2.2 times more likely than domestic US participants to suffer injury. Individuals with 3+ years of CrossFit experience were 3.3 times more likely to be injured than those with 2 or less years of experience. Participants who trained for 11+ h/week were significantly more likely to be injured than those who trained less than or equal to 10 h/week. CONCLUSIONS: As CrossFit becomes more popular, it is important to monitor the safety of its practitioners. Further studies are needed to explore how to lower this injury prevalence of 33.3%. Areas to focus on include factors that have caused the regional (international vs US states) differences, level of expertise/experience differences (advanced level vs intermediate and beginner levels), and stretching routine modifications.