Citations

Summary: Incorporation of new technologies to assist the liposuction procedure is becoming increasingly common. These technologies allow for a softer technique, balanced shaping, elimination of excess adipose tissue, and skin tightening. Some of these technologies include ultrasound (US; US-assisted liposculpture, VASER-assisted liposuction), power suction (power-assisted liposuction), radiofrequency (RF; RF-assisted lipolysis), and laser (laser-assisted liposuction). In addition, some of these devices have been shown to reduce the incidence of hematomas/inflammation and shorten recovery time. We report our experience in high-definition liposculpture of the arms in addition to new technologies to improve skin retraction, comparing their results in terms of complications, satisfaction score, and aesthetic outcomes. We included patients with mild-to-moderate arm dermatochalasis (Duncan classification) fat deposits in the upper extremities who were considered candidates for third-generation US-assisted liposculpture, power-assisted liposuction, RF-assisted lipolysis/skin tightening, and laser-assisted liposuction. A total of 683 consecutive patients met the inclusion criteria for the study. Most of them were women (n = 605, 88%). Fat grafting was performed in 80 patients (11.7%). A significant portion of the patients were secondary cases (n = 223, 33%). Age ranged from 18 to 70 years (median = 38 years). BMI ranged from 17.8 to 34.8 kg/m2 (mean = 24.3 kg/m2). RF-assisted and laser-assisted high-definition liposculpture of the arms are both effective and reproducible techniques for patients who seek an athletic and slim arm contour. A low rate of complications and high satisfaction index support our findings.

Clarkson disease, or monoclonal gammopathy–associated idiopathic systemic capillary leak syndrome (ISCLS), is a rare, relapsing-remitting disorder featuring the abrupt extravasation of fluids and proteins into peripheral tissues, which in turn leads to hypotensive shock, severe hemoconcentration, and hypoalbuminemia. The specific leakage factor(s) and pathways in ISCLS are unknown, and there is no effective treatment for acute flares. Here, we characterize an autonomous vascular endothelial defect in ISCLS that was recapitulated in patient-derived endothelial cells (ECs) in culture and in a mouse model of disease. ISCLS-derived ECs were functionally hyperresponsive to permeability-inducing factors like VEGF and histamine, in part due to increased endothelial nitric oxide synthase (eNOS) activity. eNOS blockade by administration of N (γ)-nitro-l-arginine methyl ester (l-NAME) ameliorated vascular leakage in an SJL/J mouse model of ISCLS induced by histamine or VEGF challenge. eNOS mislocalization and decreased protein phosphatase 2A (PP2A) expression may contribute to eNOS hyperactivation in ISCLS-derived ECs. Our findings provide mechanistic insights into microvascular barrier dysfunction in ISCLS and highlight a potential therapeutic approach.

Background: Caloric restriction (CR) has been recognized for its benefits in delaying age-related diseases and extending lifespan. While its effects on amyloid pathology in Alzheimer’s disease (AD) mouse models are well-documented, its effects on tauopathy, another hallmark of AD, are less explored. Objective: To assess the impact of a short-term 30% CR regimen on age-dependent spatial learning deficits and pathological features in a tauopathy mouse model. Methods: We subjected male PS19 tau P301S (hereafter PS19) and age-matched wildtype mice from two age cohorts (4.5 and 7.5 months old) to a 6-week 30% CR regimen. Spatial learning performance was assessed using the Barnes Maze test. Tau pathology, neuroinflammation, hippocampal cell proliferation, and neurogenesis were evaluated in the older cohort by immunohistochemical staining and RT-qPCR. Results: CR mitigated age-dependent spatial learning deficits in PS19 mice but exhibited limited effects on tau pathology and the associated neuroinflammation. Additionally, we found a decrease in hippocampal cell proliferation, predominantly of Iba1+ cells. Conclusions: Our findings reinforce the cognitive benefits conferred by CR despite its limited modulation of disease pathology. Given the pivotal role of microglia in tau-driven pathology, the observed reduction in Iba1+ cells under CR suggests potential therapeutic implications, particularly if CR would be introduced early in disease progression.

Abstract Context Tumor-induced osteomalacia (TIO) is a rare condition with evidence mostly derived from case reports and case series. Objective We aimed to describe the clinical characteristics of a large cohort of patients diagnosed with TIO, with a focus on patients with nonlocalizing and malignant TIO. Methods This is a retrospective cohort of patients with TIO in an academic medical center, diagnosed between January 1998 and May 2023. We describe their demographics, biochemistries, tumor features, localization, treatment, and complications. Results Of 68 patients diagnosed with TIO, 49 (72%) were localizing and 5 (7.4%) were malignant. Of 50 patients who attempted localizing procedures, 29 (58%) achieved cure. Twenty (40%) had persistent disease due to the wrong tumor targeted, or refractory or recurrent tumors, despite up to 6 procedural attempts. There was no difference in demographics, phosphorus, or baseline fibroblast growth factor-23 (FGF23) levels between localizing vs nonlocalizing groups, and malignant vs nonmalignant groups. The lower extremity was the commonest site of localization (37%), with 47% in bone and 53% in soft tissue. Sixty percent of malignant cases were located in the trunk. Tumor size correlated with peak FGF23 (R = 0.566, P < .001) but was not associated with malignancy risk (P = .479). A cut-off FGF23 of >20 times upper limit of normal in the presence of normal renal function (P = .025) and recurrence after initial cure (P = .013) were factors significantly associated with malignancy. The nonlocalizing group had lower survival than the localizing group (P = .0097). Conclusion TIO is a condition with significant morbidity. Very high FGF23 levels and disease recurrence are associated with malignant disease. Reasons behind the observation of higher mortality in nonlocalizing TIO should be further explored.

AbstractIntroductionDown syndrome (DS) is associated with multiple comorbid conditions and chronic immune dysfunction. Persons with DS who contract COVID‐19 are at high risk for complications and have a poor prognosis. We aimed to study the clinical symptoms, laboratory and biochemical profiles, radiologic findings, treatment, and outcomes of patients with DS and COVID‐19.MethodWe systematically searched PubMed, MEDLINE, Web of Science, Scopus, and the Cochrane Library using the keywords COVID‐19 or coronavirus or SARS‐CoV‐2 and DS or trisomy 21. Seventeen articles were identified: eight case reports and nine case series published from December 2019 through March 2022, with a total of 55 cases.ResultsPatients averaged 24.8 years (26 days to 60 years); 29 of the patients were male. The most common symptoms were fever, dyspnea, and cough. Gastrointestinal and upper respiratory tract symptoms were commonly reported for pediatric patients. The most common comorbidities present in patients with DS were obesity (49.0%), hypothyroidism (21.6%) and obstructive sleep apnea (15.6%). The patients were hospitalized for a mean of 14.8 days. When the patients were compared with the general COVID‐19 population, the mean number of hospitalized days was higher. Most patients had leukopenia, lymphopenia, and elevated inflammatory markers (d‐dimer and C‐reactive protein). Bilateral infiltrations and bilateral ground‐glass opacifications were frequently seen in chest radiographs and chest computed tomographic imaging. Most of the patients were treated with methylprednisolone, macrolides, and hydroxychloroquine. Of the 55 patients, 22 died. The mean age of the patients who died was 42.8 years. Mortality rate was higher in individuals with DS over 40 years of age.ConclusionMore studies are needed to better understand COVID‐19 infections among persons with DS. In addition, the study was limited by a lack of statistical analyses and a specific comparison group.

Abstract Context Spasticity is characterized by increased muscle tone and stretch reflexes, often caused by an upper motor neuron (UMN) syndrome. Many patients live with their dysfunction of their upper or lower limbs for many years and are managed by a multidisciplinary team including physical medicine and rehabilitation specialists, neurologists, and/or physical therapists in an attempt to decrease their spasticity and enhance their quality of life. Reconstructive surgery is a treatment option for many patients living with spasticity. The goal of surgery is to permanently decrease their spastic tone and improve their quality of life. Spastic hemiplegia or hemiparesis is an area of orthopedic surgery that is uniquely suited to telemedicine evaluation. Telemedicine visits can lower the threshold for patients to obtain consultation, receive second opinions, and determine whether traveling for an in-person assessment might be worthwhile, particular to larger medical centers. Objectives The objective of our study was to characterize patient perceptions of telemedicine consultation for spasticity surgery and to determine its effectiveness for indicating reconstructive procedures. Methods An electronic survey consisting of 16 questions was distributed to all patients after the virtual consultation from April 2020 to September 2022 as part of a neuro-orthopedic evaluation. Domains of inquiry included patient demographic and diagnosis information, satisfaction with provider assessment, ease of use, appointment preference, and whether surgery was eventually performed. Identifying information was voluntarily provided by patients and allowed for survey data to be linked to the medical record. Patients were included in the study if they were diagnosed with upper and/or lower extremity spasticity, were evaluated by telemedicine visit, and were over the age of 18. They were excluded from the study if they were evaluated for any condition aside from spasticity or returned an incomplete survey. Patients who completed the survey were prospectively followed through December 2022 to determine whether a subsequent in-person visit was pursued and/or reconstructive surgery was performed. Results A total of 19 of 36 patients completed surveys, for a response rate of 52.7 %. Nearly all (94.7 %, n=18) patients felt that the provider expressed maximal concern for patient questions/worries, included them in decisions regarding care, and appropriately discussed treatment strategies. Similarly, the majority (89.5 %, n=17) were maximally satisfied with explanations about their condition and would recommend the care provider to others. Most patients (84.2 %, n=16) also felt that the ease of communication via the virtual platform was very good. All patients were eventually indicated for and subsequently underwent reconstructive surgery for spasticity. Conclusions Spasticity patients were overwhelmingly satisfied with their initial virtual consultation as an alternative to face-to-face visits. Telemedicine provides a clinical opportunity for seeking information about spasticity surgery and offers a cost-effective and convenient option for patients who find travel to specialty centers prohibitive.

Background: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland neoplasm. They can present with distinct immunoprofiles, such as androgen receptor (AR) and HER-2/Neu-positivity. To date, no consensus exists on how to best manage this entity. Methods: All patients diagnosed with nonmetastatic AR+ SDC of the parotid from 2013 to 2019 treated with curative intent were included. Immunologic tumor profiling was conducted using 24 distinct markers. Kaplan–Meier analyses were used to estimate locoregional recurrence (LRR), distant control, and overall survival (OS). Results: Fifteen patients were included. Nine (60%) patients presented with T4 disease and eight (53%) had positive ipsilateral cervical lymphadenopathy. Ten (67%) patients underwent trimodality therapy, including surgery followed by adjuvant radiation and concurrent systemic therapy. The median follow-up was 5.5 years (interquartile range, 4.8–6.1). The estimated 5-year rates of LRR, distant progression, and OS were 6%, 13%, and 87%, respectively. Conclusion: Despite only including AR+ SDC of the parotid, immunoprofiles, such as expression of HER-2, were highly variable, highlighting the potential to tailor systemic regimens based on individual histologic profiles in the future. Studies with larger patient numbers using tumor-specific molecular profiling and tumor heterogeneity analyses are justified to better understand the biology of these tumors. Molecularly informed treatment approaches, including the potential use of AR- and HER-2/Neu-directed therapies upfront in the definitive setting, may hold future promise to further improve outcomes for these patients.