Case report: A novel somatic SDHB variant in a patient with bladder paraganglioma.

Background: Paragangliomas (PGL) are rare neuroendocrine tumors derived from the autonomic nervous system paraganglia. Urinary bladder paragangliomas (UBPGL) originate from the sympathetic neurons of the urinary bladder wall and represent 0.7% of all paragangliomas and <0.05% of all bladder tumors. PGL and UBPGL can be associated with SDHB, SDHD, NF1, and VHL gene variants, with the most common germline alterations found in SDHB and VHL. Case report: We report a case of a 42-year-old woman who presented with menorrhagia/hematuria, uterine leiomyomas, as well as cardiac and bladder masses. The cardiac mass was favored to be a myxoma based on clinical findings, while the bladder mass was diagnosed as UBPGL. A novel SDHB mutation (c.642G>A, p Q214Q), detected in the UBPGL, was proven to be somatic. Although this variant was seemingly synonymous, it was predicted to have a loss of function due to the splice site effect, which was further supported by the immunohistochemical loss of SDHB. Conclusion: This case highlights the challenges of diagnosing an extremely rare entity, bladder paraganglioma, with an emphasis on the multidisciplinary approach to navigate various clinical and imaging findings that may initially be misleading. In addition, a novel loss of function SDHB variant that could have been overlooked as a synonymous variant is herein reported, while also illustrating the importance of both germline and somatic mutation testing.

Electrochemical Lipolysis Induces Adipocyte Death and Fat Necrosis: In Vivo Pilot Study in Pigs.

BACKGROUND: Current minimally invasive fat reduction modalities use equipment that can cost thousands of U.S. dollars. Electrochemical lipolysis (ECLL), using low-cost battery and electrodes (approximately $10), creates acid/base within fat (width, approximately 3 mm), damaging adipocytes. Longitudinal effects of ECLL have not been studied. In this pilot study, the authors hypothesize that in vivo ECLL induces fat necrosis, decreases adipocyte number/viability, and forms lipid droplets. METHODS: Two female Yorkshire pigs (50 to 60 kg) received ECLL. In pig 1, 10 sites received ECLL, and 10 sites were untreated. In pig 2, 12 sites received ECLL and 12 sites were untreated. For ECLL, two electrodes were inserted into dorsal subcutaneous fat and direct current was applied for 5 minutes. Adverse effects of excessive pain, bleeding, infection, and agitation were monitored. Histology, live-dead (calcein, Hoechst, ethidium homodimer-1), and morphology (Bodipy and Hoechst) assays were performed on day 0 and postprocedure days 1, 2, 7, 14 (pig 1 and pig 2), and 28 (pig 2). Average particle area, fluorescence signal areas, and adipocytes and lipid droplet numbers were compared. RESULTS: No adverse effects occurred. Live-dead assays showed adipocyte death on the anode on days 0 to 7 and the cathode on days 1 to 2 (not significant). Bodipy showed significant adipocyte loss at all sites ( P < 0.001) and lipid droplet formation at the cathode site on day 2 ( P = 0.0046). Histology revealed fat necrosis with significant increases in average particle area at the anode and cathode sites by day 14 (+277.3% change compared with untreated, P < 0.0001; +143.4%, P < 0.0001) and day 28 (+498.6%, P < 0.0001; +354.5%, P < 0.0001). CONCLUSIONS: In vivo ECLL induces fat necrosis in pigs. Further studies are needed to evaluate volumetric fat reduction. CLINICAL RELEVANCE STATEMENT: In vivo ECLL induces adipocyte death and fat necrosis. ECLL has the potential to be utilized in body fat contouring.

In vivo electrochemical lipolysis of fat in a Yucatan pig model: A proof of concept study.

OBJECTIVES: Traditional fat contouring is now regularly performed using numerous office- based less invasive techniques. However, some limitations of these minimally invasive techniques include high cost or limited selectivity with performing localized contouring and reduction of fat. These shortcomings may potentially be addressed by electrochemical lipolysis (ECLL), a novel approach that involves the insertion of electrodes into tissue followed by application of a direct current (DC) electrical potential. This results in the hydrolysis of tissue water creating active species that lead to fat necrosis and apoptosis. ECLL can be accomplished using a simple voltage-driven system (V-ECLL) or a potential-driven feedback cell (P-ECLL) both leading to water electrolysis and the creation of acid and base in situ. The aim of this study is to determine the long-lasting effects of targeted ECLL in a Yucatan pig model. METHODS: A 5-year-old Yucatan pig was treated with both V-ECLL and P-ECLL in the subcutaneous fat layer using 80:20 platinum:iridium needle electrodes along an 8 cm length. Dosimetry parameters included 5 V V-ECLL for 5, 10, and 20 minutes, and -1.5 V P-ECLL, -2.5 V P-ECLL, -3.5 V P-ECLL for 5 minutes. The pig was assessed for changes in fat reduction over 3 months with digital photography and ultrasound. After euthanasia, tissue sections were harvested and gross pathology and histology were examined. RESULTS: V-ECLL and P-ECLL treatments led to visible fat reduction (12.1%-27.7% and 9.4%-40.8%, respectively) and contour changes across several parameters. An increased reduction of the superficial fat layer occurred with increased dosimetry parameters with an average charge transfer of 12.5, 24.3, and 47.5 C transferred for 5 V V-ECLL for 5, 10, and 20 minutes, respectively, and 2.0, 11.5, and 24.0 C for -1.5 V P-ECLL, -2.5 V P-ECLL, -3.5 V P-ECLL for 5 minutes, respectively. These dose-dependent changes were also evidenced by digital photography, gross pathology, ultrasound imaging, and histology. CONCLUSIONS: ECLL results in selective damage and long-lasting changes to the adipose layer in vivo. These changes are dose-dependent, thus allowing for more precise contouring of target areas. P-ECLL has greater efficiency and control of total charge transfer compared to V-ECLL, suggesting that a low-voltage potentiostat treatment can result in fat apoptosis equivalent to a high-voltage DC system.

Characterization and Roles of Membrane Lipids in Fatty Liver Disease.

Obesity has reached global epidemic proportions and it affects the development of insulin resistance, type 2 diabetes, fatty liver disease and other metabolic diseases. Membrane lipids are important structural and signaling components of the cell membrane. Recent studies highlight their importance in lipid homeostasis and are implicated in the pathogenesis of fatty liver disease. Here, we discuss the numerous membrane lipid species and their metabolites including, phospholipids, sphingolipids and cholesterol, and how dysregulation of their composition and physiology contribute to the development of fatty liver disease. The development of new genetic and pharmacological mouse models has shed light on the role of lipid species on various mechanisms/pathways; these lipids impact many aspects of the pathophysiology of fatty liver disease and could potentially be targeted for the treatment of fatty liver disease.

Exploring feedback-controlled versus open-circuit electrochemical lipolysis in ex vivo and in vivo porcine fat: A feasibility study.

OBJECTIVES: Minimally invasive fat sculpting techniques are becoming more widespread with the development of office-based devices and therapies. Electrochemical lipolysis (ECLL) is a needle-based technology that uses direct current (DC) to electrolyze tissue water creating acid and base in situ. In turn, fat is saponified and adipocyte cell membrane lysis occurs. The electrolysis of water can be accomplished using a simple open-loop circuit (V-ECLL) or by incorporating a feedback control circuit using a potentiostat (P-ECLL). A potentiostat utilizes an operational amplifier with negative feedback to allow users to precisely control voltage at specific electrodes. To date, the variation between the two approaches has not been studied. The aim of this study was to assess current and charge transfer variation and lipolytic effect created by the two approaches in an in vivo porcine model. METHODS: Charge transfer measurements from ex vivo V-ECLL and P-ECLL treated porcine skin and fat were recorded at -1 V P-ECLL, -2 V P-ECLL, -3 V P-ECLL, and -5 V V-ECLL each for 5 min to guide dosimetry parameters for in vivo studies. In follow-up in vivo studies, a sedated female Yorkshire pig was treated with both V-ECLL and P-ECLL across the dorsal surface over a range of dosimetry parameters, including -1.5 V P-ECLL, -2.5 V P-ECLL, -3.5 V P-ECLL, and 5 V V-ECLL each treated for 5 min. Serial biopsies were performed at baseline before treatment, 1, 2, 7, 14, and 28 days after treatment. Tissue was examined using fluorescence microscopy and histology to compare the effects of the two ECLL approaches. RESULTS: Both V-ECLL and P-ECLL treatments induced in-vivo fat necrosis evident by adipocyte membrane lysis, adipocyte denuclearization, and an acute inflammatory response across a 28-day longitudinal study. However, -1.5 V P-ECLL produced a smaller spatial necrotic effect compared to 5 V V-ECLL. In addition, 5 V V-ECLL produced a comparable necrotic effect to that of -2.5 V and -3.5 V P-ECLL. CONCLUSIONS: V-ECLL and P-ECLL at the aforementioned dosimetry parameters both achieved fat necrosis by adipocyte membrane lysis and denuclearization. The -2.5 V and -3.5 V P-ECLL treatments created spatially similar fat necrotic effects when compared to the 5 V V-ECLL treatment. Quantitatively, total charge transfer between dosimetry parameters suggests that -2.5 V P-ECLL and 5 V V-ECLL produce comparable electrochemical reactions. Such findings suggest that a low-voltage closed-loop potentiostat-based system is capable of inducing fat necrosis to a similar extent compared to that of a higher voltage direct current system.

Evaluation of Characteristics and Outcomes for Patients with Diabetic Ketoacidosis (DKA) With and Without COVID-19 in Elmhurst Queens During Similar Three-Month Periods in 2019 and 2020.

Aim There are reports of COVID-19 patients presenting with new onset diabetes, diabetic ketoacidosis (DKA), and hyperosmolar hyperglycemic syndrome (HHS). We compared the characteristics of patients with DKA with and without COVID-19 and their effect on mortality. Research design and methods A retrospective study at Elmhurst Hospital Center in Queens, New York was performed using ICD-10 codes to identify patients with DKA from March 1 to May 31 in 2019 and 2020. Results While comparing COVID-19 patients with DKA to the DKA patients without COVID-19 in both 2019 and 2020, hispanic patients, males, and type 2 diabetes predominated. COVID-19 patients were older (p=0.010), had more hypertension (p=0.002), and severe lactic acidosis (p=0.006). Mortality for DKA patients with COVID-19 was 57%, for DKA patients without COVID-19 it was 2.1% (p=0.0001), and for diabetic patients (no DKA) with COVID-19 it was 39% (p=0.035). Within the COVID-19 group, older age (mean age 65), (p=0.014), elevated CRP (p=0.012), low O2 saturation (p=0.001), and beta blocker use (P=0.01) were associated with increased mortality. Conclusions COVID-19 patients are older, have a history of hypertension, more severe DKA and lactic acidosis than patients without COVID-19. There was no increase in DKA with HHS. DKA, but not diabetic parameters, hypertension, and older age predicted a poor outcome.

A Case of Refractory Myxedema Coma.

We present a case of myxedema coma refractory to traditional treatments. Morbidity and mortality from myxedema coma are frequently due to a missed or delayed diagnosis. It tends to respond very well to intravenous levothyroxine replenishment as long as this treatment is initiated early. We report a case of a 71-year-old man who presented with altered mental status and severe bradycardia who was promptly diagnosed with myxedema coma on laboratory studies sent in the emergency department (thyroid-stimulating hormone 94.74, free T4 0.17, and free T3 0.69). However, while the diagnosis was recognized immediately, and he was treated aggressively with intravenous thyroxine replacement, he strangely remained refractory to treatment for a prolonged period of time. While he did respond to intravenous thyroxine initially, he dramatically decompensated each time he was transitioned to oral therapy. This case brings to question why rarely certain patients fail the transition to oral therapy, and how to treat these patients.

Computational analysis of six optical coherence tomography systems for vocal fold imaging: A comparison study.

OBJECTIVES: There have been many advancements in laryngeal imaging using optical coherence tomography (OCT), with varying system design and probes for use in research, office, and operating room settings. We evaluated the performance of six distinct OCT systems in imaging porcine vocal folds (cords) using computational image processing and segmentation. METHODS: Porcine vocal folds were scanned using six OCT systems. Imaging system and probe performance were quantitatively assessed for signal penetration, layer differentiation, and epithelium (EP) measurement. Fitted exponential decay curves with corresponding α constant and intensity thresholding segmentation were utilized to quantify the aforementioned parameters. RESULTS: The smallest average α constant and deepest signal penetration was of the SS-OCT 1700 nm 90 kHz microscope system (α = -1.74), followed by the SS-OCT 1310 nm 200 kHz VCSEL microscope system (α = -1.99), and SS-OCT 1310 nm 50 kHz rigid forward viewing endoscope system (α = -2.23). The EP was not readily visualized for three out of six systems, but was detected using automated segmentation. Average EP thickness (mean ± SD) was calculated as 55.79 ± 31.86 µm which agrees favorably with previous literature. CONCLUSION: Comparisons of OCT systems are challenging, as they encompass different probe design, optical path, and lasers, depending on application. Practical evaluation of different systems using computer based quantitative image processing and segmentation revealed basic, constructive information, such as EP measurements. To further validate the comparisons of system performance with clinical usability, in vivo human laryngeal imaging will be conducted. Further development of automated image processing and segmentation can be useful in rapid analysis of information. Lasers Surg. Med. 51:412-422, 2019. © 2019 Wiley Periodicals, Inc.