Ultrasound Appearance of Intravascular Uterine Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): A Case Report.

A 43-year-old patient with a history of uterine fibromatosis was referred to our hospital for menometrorrhagia and pelvic pain. At the pelvic ultrasound, a highly-vascularized myometrial lesion in volumetric increase was described. An elongated, solid, hypoechoic, painless, and highly vascularized left parauterine mass was identified. On histological examination, a uterine smooth muscle tumor of uncertain malignant potential (STUMP) with intravascular invasion of the left uterine vein was diagnosed. The adnexa and peritoneum were free of disease. On a retrospective evaluation of the ultrasound images, we noticed that the intravascular lesion showed sonographic features comparable to the original mass. Moreover, the Color Doppler (CD) analysis revealed an interrupted blood flow within the left uterine vein. In this case, the ultrasound proved to be an accurate diagnostic tool. When inhomogeneous uterine masses are suspected, and a parauterine/paraadnexal mass surrounded by irregular vessels are identified, the sonographer should take into account a risk of intravascular invasion. The patency of uterine and ovarian vessels should be accurately evaluated, to guide a tailored patient surgical approach.

Coronary intravascular lithotripsy in contemporary practice: challenges and opportunities in coronary intervention.

Percutaneous coronary intervention (PCI) of calcified coronary arteries is associated with poor outcomes. Poorly modified calcified lesion hinders the stent delivery, disrupts drug-carrying polymer, impairs drug elution kinetics and results in under-expanded stent (UES). UES is the most common cause of acute stent thrombosis and in-stent restenosis after PCI of calcified lesions. Angiography has poor sensitivity for recognition and quantification of coronary calcium, thereby mandating the use of intravascular imaging. Intravascular imaging, like intravascular ultrasound and optical coherence tomography, has the potential to accurately identify and quantify the coronary calcium and to guide appropriate modification device before stent placement. Available options for the modification of calcified plaque include modified balloons (cutting balloon, scoring balloon and high-pressure balloon), atherectomy devices (rotational atherectomy and orbital atherectomy) and laser atherectomy. Coronary intravascular lithotripsy (IVL) is the newest addition to the tool box for calcified plaque modification. It produces the acoustic shockwaves, which interact with the coronary calcium to cause multiplanar fractures. These calcium fractures increase the vessel compliance and result in desirable minimum stent areas. Coronary IVL has established its safety and efficacy for calcified lesion in series of Disrupt CAD trials. Its advantages over atherectomy devices include ease of use on workhorse wire, ability to modify deep calcium, no debris embolization causing slow flow or no-flow and minimal thermal injury. It is showing promising results in modification of difficult calcified lesion subsets such as calcified nodule, calcified left main bifurcation lesions and chronic total occlusion. In this review, authors will summarize the mechanism of action for IVL, its role in contemporary practice, evidence available for its use, its advantages over atherectomy devices and its imaging insight in different calcified lesion scenarios.

Shock the rock with coronary intravascular lithotripsyPresence of coronary calcium during stenting is associated with the risk of stent under expansion. It's imperative to adequately modify this coronary calcium before placing the stent. Till recent past, the most effective method for calcium modification is debulking it with rotational artherectomy, which is associated with the risk of coronary perforation, slow flow or abrupt vessel closure. Recently, a balloon-based lithotripsy device has established its safety and efficacy for treating such lesions. Coronary intravascular lithotripsy (IVL) is an easy to use calcium modification device and is associated with almost negligible complications, when compared with artherectomy devices. In this review, we will discuss the mechanism of IVL action and its use in different scenarios of calcified coronary artery disease.

A Phase I, Open-Label, Sequential, Single-Dose Clinical Trial to Evaluate the Pharmacokinetic, Pharmacodynamic, and Safety of IVL3001, a Finasteride-Based Novel Long-Acting Injection for Androgenetic Alopecia.

INTRODUCTION: Hair loss is driven by multiple factors, including genetics. Androgenetic alopecia (AGA) is a condition in which treatments necessitate prolonged compliance with prescribed medications. We have developed IVL3001, a long-acting injectable (LAI) formulation of finasteride encapsulated within poly lactic-co-glycolic acid microspheres, to enhance the efficacy of the finasteride and to achieve consistent positive outcomes in adults. An open-label, sequential, single-dose phase I clinical trial was designed to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic (PD) of IVL3001. METHODS: A total of 40 non-smoking, healthy adult males were divided into three cohorts where the IVL3001 group received a single subcutaneous injection of 12-36 mg IVL3001 and 1 mg finasteride (Propecia®) once daily for 28 days. The plasma concentrations of finasteride, dihydrotestosterone (DHT), and testosterone were measured using liquid chromatography-tandem mass spectrometry. The tolerability of the injections was assessed, and compartment models were developed to predict the effective dose and assess PK/PD profiles. RESULTS: IVL3001 and finasteride 1 mg tablets were well tolerated. IVL3001 showed consistent plasma concentrations without bursts or fluctuations. Consistent with its mechanism of action, IVL3001 reduced DHT levels. Simulation data showed that the administration of 12-36 mg of IVL3001 every 4 weeks achieved plasma concentrations similar to finasteride, with comparable DHT reduction. CONCLUSION: The present study represents the first clinical trial to evaluate the safety, pharmacokinetic (PK), pharmacodynamic (PD), and tolerability of finasteride long-acting injectables (LAI) in adults. The rapid onset of action sustained effective drug concentration and the prolonged half-life of IVL3001 suggest that it offers multiple benefits over conventional oral formulations in terms of therapeutic response and compliance. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04945226.

Intravascular lithotripsy in peripheral lesions with severe calcification and its use in TAVI procedure - a meta-analysis.

Background: Heavily calcified peripheral artery lesions increase the risk of vascular complications, constituting a severe challenge for the operator during catheter-based cardiovascular interventions. Intravascular Lithotripsy (IVL) technology disrupts subendothelial calcification by using localized pulsative sonic pressure waves and represents a promising technique for plaque modification in patients with severe calcification in peripheral arteries. Purpose: Our aim was to systematically review and summarize available data regarding the safety and efficacy of IVL in preparing severely calcified peripheral arteries and its use in Transcatheter Aortic Valve Implantation (TAVI). Patients and methods: This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies assessing the characteristics and outcomes of patients undergoing IVL in the peripheral vasculature. The diameter of the vessel lumen before and after IVL was estimated. The occurrence of peri-procedural complications was assessed using a random-effects model. Results: 20 studies with a total of 1,223 patients with heavily calcified peripheral lesions were analysed. The mean age of the cohort was 70.6 ± 17.4 years. Successful IVL delivery achieved in 100% (95% CI: 100%-100%, I2 = 0%), with an increase in the luminal diameter (SMD: 4.66, 95% CI: 3.41-5.92, I2 = 90.8%) and reduction in diameter stenosis (SMD: -4.15, 95% CI: -4.75 to -3.55, I2 = 92.8%), and a concomitant low rate of complications. The procedure was free from dissection in 97% (95% CI: 91%-100%, I2 = 81.4%) while dissections of any type (A, B, C, or D) were observed in 6% (95% CI: 2%-10%, I2 = 85.3%) of the patients. Several rare cases of abrupt closure, no-reflow phenomenon, perforation, thrombus formation, and distal embolization were recorded. Finally, the subgroup analysis of patients who underwent a TAVI with IVL assistance presented successful implantation in 100% (95% CI: 100%-100%, I2 = 0%) of the cases, with only 4% (95% CI: 0%-12%, I2 = 68.96%) presenting dissections of any sort. Conclusions: IVL seems to be an effective and safe technique for modifying severely calcified lesions in peripheral arteries and it is a promising modality in TAVI settings. Future prospective studies are needed to validate our results.

Intravascular lithotripsy-assisted percutaneous deep vein arterialization for no-option chronic limb-threatening patients and heavily calcified tibial occlusive disease.

PURPOSE: To report the first chronic limb-threatening ischemia (CLTI) patients who underwent an intravascular lithotripsy (IVL)-assisted percutaneous deep vein arterialization (pDVA). CASE REPORT 1: An 81-year-old patient presented with CLTI and a heavily calcified lesion of the popliteal artery and tibioperoneal trunk (TPT), with a distal tibial and foot arch occlusion. The patient underwent IVL and drug-coated balloon angioplasty for the distal popliteal artery and of the TPT to improve the inflow prior to pDVA. The wound situation remained stable without secondary procedure until the patient`s deaths due to complications of urosepsis 3 months later. CASE REPORT 2: A 64-year-old patient with rest pain of the left limb with a single-vessel tibial run-off (peroneal artery) and occluded pedal arch was treated with 3.5 mm IVL followed by a successful pDVA as mentioned above. IVL performed in the proximal posterior tibial artery to optimize the inflow to the circuit and change the compliance of the crossing point from the arterial to the vein system. The patient underwent repeat angioplasty of the plantar vein arch 5 months after the index procedure and thereafter remained asymptomatic during 2 years of follow-up. CONCLUSION: The combined use of IVL and pDVA could improve the patency of the reconstruction with clinical benefits in no-option CTLI patients.

Effects on keratinocytes of the traditional combination of herb extract (Royal Oji Complex) implicated the improvement of young children's skin moisture and barrier.

BACKGROUND: Natural products are often friendly and can be used on children's skin after systematic and careful research. Therefore, in this study, the Royal Oji Complex (ROC), a product with natural ingredients, was used to study their effectiveness on keratinocytes taken from the skin of children from 0 to 3 years old. METHOD: Normal human epidermal keratinocytes and tissue-isolated keratinocytes (TIKC) from young donors were treated with three different concentrations of ROC: 0.1, 1, and 10 ppm. The mRNA expression of the epidermal barrier's essential genes, such as hyaluronic acid synthase 3 (Has3), involucrin (IVL), loricrin (LOR), and claudin-1 (CLD1) was investigated using qRT-PCR. Ceramide content was measured by ELISA, with retinoic acid (R.A.) and amarogentin (AMA) serving as positive controls. RESULTS: ROC significantly elevated HAS3 gene expression in HEKn cells, especially at 10 ppm, indicating potential advantages for skin hydration in young infants. IVL increased at first but decreased as ROC concentrations increased. LOR was upregulated at lower ROC concentrations but reduced at higher doses. CLD1 gene expression increased considerably in HEKn but reduced with increasing ROC doses. Ceramide concentration increased somewhat but not significantly at 10 ppm. CONCLUSION: ROC shows potential in altering keratinocyte gene expression, with unique responses in HEKn and TIKC from young donors. While changes in ceramide content were insignificant, these results help to comprehend ROC's multiple effects on young children's skin.

Intravascular Lithotripsy-Assisted Transfemoral Transcatheter Aortic Valve Implantation in Patients with Severe Iliofemoral Calcifications: Expanding Transfemoral Indications.

(1) Background: Transfemoral transcatheter aortic valve implantation (TAVI) has become the standard treatment for most patients with severe symptomatic aortic stenosis. Intravascular lithotripsy may facilitate transfemoral TAVI (IVL-TAVI) even in patients with severely calcified iliofemoral disease. We assessed technical aspects and clinical outcomes of this novel approach compared to alternative transaxillary access (TAX-TAVI). (2) Methods: IVL-TAVI was performed for severe iliofemoral calcifications precluding standard transfemoral access in 30 patients from 2019 to 2022 at a single academic heart center. IVL was performed as part of the TAVI procedure in all cases. Results were compared to a control group of 44 TAX-TAVI procedures performed for the same indication from 2016 to 2021. The safety outcome was a composite of all-cause death, stroke, access-related bleeding ≥ type 2 within 24 h and major vascular access site complications at 30 days. The efficacy outcome was defined as a technical success according to VARC-3. (3) Results: Median age was 78.2 [74.3, 82.6] years, 45.9% were female and mean STS-PROM was 3.6% [2.3, 6.0]. Iliofemoral calcifications were more severe in the IVL-TAVI vs. TAX-TAVI groups (lesion length: 63.0 mm [48.6, 80.3] vs. 48.5 mm [33.1, 68.8]; p = 0.043, severe calcification at target lesion: 90.0% vs. 68.2%; p = 0.047, and median arc calcification 360.0° [297.5, 360.0] vs. 360.0° [180.0, 360.0]; p = 0.033). Technical success was achieved in 93.3% vs. 81.8% (p = 0.187) in IVL- and TAX-TAVI and the safety outcome occurred in 10.0% vs. 31.8% in IVL- and TAX-TAVI (p = 0.047), respectively. (4) Conclusions: IVL-assisted transfemoral TAVI was feasible and safe with favorable outcomes compared to TAX-TAVI. IVL may further expand the number of patients eligible for transfemoral TAVI and may help overcome limitations of an alternative access.

Distal AVF creation with marginal calcified radial artery: Multicentric experience of intraoperative intravascular lithotripsy.

INTRODUCTION: The first-choice vascular access to starting dialysis in patients with End Stage Renal Disease (ESRD) is autogenous distal arteriovenous-fistula (AVF) to spare vascular district avoiding proximal fistula complications. One of most significant exclusion criteria to create distal AVF is still now the presence of huge calcification of the feeding artery due to large numbers of early failure (EF) and failure in maturation (FTM). In recent years the possibility to use new devices able to deliver intravascular lithotripsy (IVL) to treat high calcified stenosis could be a possibility to recruit these marginal arteries to create distal AVF. METHODS: ESRD patients with totally calcified radial artery wall were enrolled to participate to this prospective, single arm, multicentric study. The selected patients were treated with intraoperative IVL at surgical time, during anastomosis creation to soften calcified radial artery. Patients were followed 1 month after surgery with eco-doppler, for flow and vessels maturation assessment. At 3 month was investigated how many patients have started dialysis treatment with two needle cannulation and good efficiency. RESULTS: Nineteen distal forearm radio-cephalic fistula were built in 19 patients. One-month doppler assessment showed mean AVF flow of 743 ml/min and efferent vein caliper of 6.46 mm. At 3 months 14 patient have started stable 2 needles dialysis (other three patients were not yet dialysis dependent CKD). Were observed one immediate failure, one failure in maturation, and two late failures at 4 and 16 months respectively. Sixteen months primary and secondary patency was 78.9% and 89.5% respectively. CONCLUSION: These results showed how intraoperative IVL could help to recruit huge calcified marginal artery to create autogenous distal forearm AVF, avoiding proximal AVF, risking distal ischemia syndrome, and sparing vascular district to eventually rebuilt more proximal AVF in future.

Uterine intravascular leiomyomatosis involves the heart: a case report and literature review.

Background: Intravascular leiomyomatosis (IVL) of the uterus is extremely rare in clinical practice, often involving the pelvic and abdominal veins. Involvement of the heart and pulmonary arteries is rarer but can lead to severe clinical outcomes. It is difficult to diagnose the disease before operation, and most of them are found accidentally during the operation or postoperative pathology of uterine fibroids. This article will report a special case of IVL involving the heart, and comprehensively analyze and discuss the relevant domestic and foreign literature. Through real clinical cases, we hope to understand the core characteristics of this disease to guide clinical diagnosis and treatment. Case Description: Here, we present the case of a 47-year-old woman with intrauterine venous leiomyomatosis whose tumor had spread to the right atrium. The patient lacked any distinct clinical symptoms. During uterine fibroid surgery, the tumor bolt was unintentionally discovered. The combined utility of multiple disciplines resulted in total removal of the tumor thrombus in the patient's venous system and right atrium during the same procedure. Following surgery, the patient achieved a significant recovery. After a follow-up of 2 years, there was no sign of neoplasm recurrence. Conclusions: IVL mainly occurs in premenopausal women. The early clinical manifestations are non-specific, and preoperative diagnosis is difficult. In order to improve the preoperative diagnosis rate, preoperative examination should be strengthened for patients with large uterine fibroids, long duration, chest tightness, shortness of breath, syncope and other medical history. During the operation, the pelvic and abdominal vessels should be comprehensively explored, and all intravascular lesions should be removed at one time, especially for those involving the heart, which often requires multidisciplinary collaboration. Complete resection of the lesion is the key factor affecting the recurrence. Endocrine therapy is an option for postoperative treatment, and it is used selectively according to the specific condition of the patient to reduce the risk of recurrence.

Intravascular Lymphoma-Associated Stroke: A Systematic Review of Case Studies.

Intravascular lymphoma (IVL) is an aggressive systemic large B-cell lymphoma that is a rare cause of stroke. The clinical characteristics of stroke associated with IVL remain underexplored, contributing to diagnostic complexities and a high mortality rate. This study endeavors to elucidate the salient clinical and investigative features of stroke linked to this condition. A systematic review was performed using the PubMed database from the incident to August 2023 including search categories for IVL and stroke. All studies, excluding review articles, were included in this study. There were 58 cases with a confirmed diagnosis of IVL associated with stroke, with a mean age of 62.9 ± 9.6 years (female 50%). Classical lateralizing stroke symptoms were noted in only 69% of cases. Other clinical syndromes included altered sensorium (31%), rapidly progressive cognitive impairment (23%), seizures (22%), and gait disturbances (19%). Common hematological abnormalities included elevated lactate dehydrogenase (LDH, 97%), erythrocyte sedimentation rate (ESR, 79%), C-reactive protein (CRP, 61%), interleukin-2, microglobulins, and cerebrospinal fluid (CSF) protein. CSF flow cytometry was not diagnostic, and cytology was mostly negative. The dynamic pattern for DWI/T2 lesions was predominant and primarily located in the subcortical regions. Diffuse background slowing (64%) was a major finding in the electroencephalogram. Seventy-one percent of cases died (n=45) mostly due to delayed diagnosis. Only 31% were treated with first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisone) chemotherapy, among whom 25% died. This study suggests that IVL-associated strokes carry a high mortality rate, largely due to challenges in timely diagnosis and therapy. Unlike classical stroke syndrome, key indicators to aid in early diagnosis include a clinical syndrome of multiple non-lateralizing neurological symptoms, dynamic MRI DWI/T2-lesions primarily located in subcortical regions, elevated serum LDH, ESR, CRP, interleukins, microglobulin, CSF protein, and CSF polymerase chain reaction analysis, apart from tissue examination. Larger studies should be performed to establish diagnostic and predictive scores.

Estudo prospectivo randomizado comparando dois métodos de tratamento clínico da radiculopatia cervical: resultados preliminares / Prospective randomized study comparing two methods of clinical treatment of cervical radiculopathy: preliminary results

A imobilização com colar cervical e uso concomitante de antiinflamatório não esteroidal foi eficaz na diminuição da dor e restrição física, porém, não ficaram evidentes diferenças estatisticamente significativas entre a utilização de órtese comum ou emissora de IVL (AU)