Biocompatible 3D-Printed Devices With Adipose Stem Cells in the Regenerative Process of Sciatic Nerve Lesions in Rodent Models: An Experimental Study.

INTRODUCTION: Peripheral nerve injuries are a significant clinical challenge. The rat sciatic nerve serves as an ideal model for studying nerve regeneration. Extensive research has been conducted to unravel the intricate mechanisms involved in peripheral nerve regeneration, aiming to develop effective therapeutic strategies for nerve injury patients. Research including different types of materials that can be used as nerve guides like synthetic polymers have been investigated for their biocompatibility and molding properties. Among multiple stem cell types, adipose-derived stem cells (ASCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), and induced pluripotent stem cells (iPSCs) have shown neuroprotective and regenerative important properties. METHODS: The purposes of our study were to develop a protocol for rat sciatic nerve injury treated with 3D-printed guide and adipose stem cells to investigate nerve regeneration through histologic examination and biomechanical characteristics of muscular tissue. We use 20 (100%) male Wistar rats, measuring between 350 g ± 35 g, who underwent complete transection of the right sciatic nerve, resulting in a 1 cm defect. The group was separated into three subgroups: the first subgroup (n = 8) was treated with a 3D-printed guide with adipose stem cells, the second subgroup (n = 8) was treated with a 3D-printed guide without adipose stem cells, and the third subgroup (n = 4) was the control group. At four, eight, and 12 weeks, we measured with ultrasonography the grade of muscular atrophy. At 12 weeks, we harvested the sciatic nerve and performed a histological examination and mechanical investigation of the tibialis anterior muscle. RESULTS: On the examined specimen of the first subgroup, cross-sectioned nerve structures were present, surrounded by a mature fibro-adipose connective tissue, with blood vessels. In the second subgroup, no nerve structure was observed on the examined sections, but in the polymorphic inflammatory infiltrate and control group, no signs of regeneration were found. CONCLUSIONS: The present study shows a promising potential when utilizing adipose stem cell-based therapies for promoting peripheral nerve regeneration following large (>1 cm) nerve defects knowing that at this size, regeneration is impossible with known treatments.

Metastatic Nodular Melanoma with Angiosarcomatous Transdifferentiation-A Case Report and Review of the Literature.

Diagnosing cutaneous melanomas relies mainly on histopathological analysis, which, in selected cases, can be aided by immunohistochemical evaluation of conventional melanocytic markers. Nevertheless, these malignancies, particularly in metastatic settings, may display divergent differentiation with unusual histological and immunohistochemical features. In this context, we present the case of a 65-year-old male diagnosed with typical superficial spreading melanoma who developed recurrence and metastatic lesions featuring angiosarcomatous differentiation. The diagnosis of the initial tumour and the subsequently dedifferentiated lesions was confirmed by ample immunohistochemical analysis, which included several melanocytic markers, as well as mesenchymal and vascular markers. The recurrent tumour and lymph nodes metastases were completely negative for Melan-A and PRAME, and focally positive for SOX10. Additionally, they also displayed diffuse, intense positivity for CD10 and WT1 and focal positivity for CD99, ERB, and CD31. Thus, the diagnosis of primary cutaneous melanoma with recurrent and metastatic divergent angiosarcomatous differentiation was established. This occurrence is particularly rare and can pose important diagnostic challenges. Therefore, in addition to presenting this highly unusual case, we also performed a comprehensive review of the literature on divergent differentiation in melanomas.

Pleomorphic Liposarcoma Unraveled: Investigating Histopathological and Immunohistochemical Markers for Tailored Diagnosis and Therapeutic Innovations.

Liposarcomas are some of the most challenging soft tissue tumors and are subclassified into multiple subtypes with special histologic and molecular features. The peculiarities of each histopathological subtype influence the clinical behavior, management, and treatment of these neoplasms. For instance, well-differentiated liposarcomas are common soft tissue malignancies and usually display a favorable outcome. On the other hand, pleomorphic liposarcoma is the rarest, yet the most aggressive subtype of liposarcoma. This histopathological diagnosis may be challenging due to the scarce available data and because pleomorphic liposarcomas can mimic other pleomorphic sarcomas or other neoplasms of dissimilar differentiation. Nevertheless, the correct diagnosis of pleomorphic liposarcoma is of utmost importance as such patients are prone to develop local recurrences and metastases. Treatment usually consists of surgical excision along with radiotherapy and follow-up of the patients. Therefore, this review aims to assess the complex clinical, histological, and immunohistochemical features of liposarcomas in order to establish how these characteristics influence the management and prognosis of the patients, emphasizing the particularities of pleomorphic liposarcoma.

Free automatic software for quality assurance of computed tomography calibration, edges and radiomics metrics reproducibility.

PURPOSE: To develop a QA procedure, easy to use, reproducible and based on open-source code, to automatically evaluate the stability of different metrics extracted from CT images: Hounsfield Unit (HU) calibration, edge characterization metrics (contrast and drop range) and radiomic features. METHODS: The QA protocol was based on electron density phantom imaging. Home-made open-source Python code was developed for the automatic computation of the metrics and their reproducibility analysis. The impact on reproducibility was evaluated for different radiation therapy protocols, and phantom positions within the field of view and systems, in terms of variability (Shapiro-Wilk test for 15 repeated measurements carried out over three days) and comparability (Bland-Altman analysis and Wilcoxon Rank Sum Test or Kendall Rank Correlation Coefficient). RESULTS: Regarding intrinsic variability, most metrics followed a normal distribution (88% of HU, 63% of edge parameters and 82% of radiomic features). Regarding comparability, HU and contrast were comparable in all conditions, and drop range only in the same CT scanner and phantom position. The percentages of comparable radiomic features independent of protocol, position and system were 59%, 78% and 54%, respectively. The non-significantly differences in HU calibration curves obtained for two different institutions (7%) translated in comparable Gamma Index G (1 mm, 1%, >99%). CONCLUSIONS: An automated software to assess the reproducibility of different CT metrics was successfully created and validated. A QA routine proposal is suggested.

Primary Undifferentiated/Dedifferentiated Cutaneous Melanomas-A Review on Histological, Immunohistochemical, and Molecular Features with Emphasis on Prognosis and Treatment.

Diagnosing cutaneous melanoma is usually straightforward based on these malignancies' histopathological and immunohistochemical features. Nevertheless, melanomas can imitate various other neoplasms, sometimes lacking the expression of conventional melanocytic markers and expressing non-melanocytic ones. Furthermore, divergent differentiation is more often encountered in metastatic melanomas and is still poorly described in primary cutaneous melanomas, and little is known about these patients' prognosis and therapeutic approach. Therefore, we reviewed the literature on undifferentiated/dedifferentiated cutaneous melanomas, and we discuss the histological, immunohistochemical, and molecular profiles of undifferentiated/dedifferentiated cutaneous melanomas to understand these peculiar lesions better and improve their diagnostic algorithm. In addition to this, we also discuss how different genetic mutations may influence prognosis and become potential therapeutic targets.

The Conundrum of Dedifferentiation in a Liposarcoma at a Peculiar Location: A Case Report and Literature Review.

Dedifferentiated liposarcoma of the deep soft tissue of the lower extremities is an infrequent finding. Myxoid liposarcoma is considered the most common soft tissue neoplasia arising in this anatomic region. Divergent differentiation usually occurs within well-differentiated liposarcoma and is exceedingly rare in a myxoid liposarcoma. We report a 32-year-old man who developed a dedifferentiated liposarcoma of the thigh on the background of a pre-existing myxoid liposarcoma. The gross examination of the surgical specimen showed a 11/7/2 cm tumour mass with solid tan-grey areas and focal myxoid degeneration. The microscopic examination revealed a malignant lipogenic proliferation, containing round cells with hyperchromatic nuclei and atypical lipoblasts, confined to the basophilic stroma with a myxoid aspect. Abrupt transition towards a hypercellular, non-lipogenic area consisting of highly pleomorphic spindle cells with atypical mitotic figures was also noted. Immunohistochemical staining was performed. Tumour cells in the lipogenic area were intensely positive for S100 and p16, and CD34 staining highlighted an arborizing capillary network. The dedifferentiated tumour areas showed positive MDM2 and CDK4 staining within neoplastic cells, with the Ki 67 proliferation marker expressed in approximately 10% of the cells. Wild-type TP53 protein expression pattern was documented. Thus, the diagnosis of a dedifferentiated liposarcoma was established. This paper aims to provide further knowledge about liposarcomas with divergent differentiation at peculiar locations, emphasizing the importance of histopathologic examination and immunohistochemical analysis for establishing the diagnosis and assessing the therapeutic response and prognosis of this condition.

Basal Cell Carcinoma-A Retrospective Descriptive Study Integrated in Current Literature.

Basal cell carcinoma (BCC) is considered to be the most common cancer in humans. It has a slow growth rhythm, and for this reason, metastases are rare. For our retrospective study, we selected 180 patients from those who underwent surgery for a variety of skin tumours between January 2019 and August 2022 and whose histopathological examination revealed basal cell carcinoma. All surgeries were performed by plastic surgeons at the "St. John" hospital in Bucharest. The aim of this article is to provide observational data regarding BCC-in terms of histopathology and diagnostic and therapeutic management and to integrate these data into the current knowledge of this pathology.

Negative Pressure Wound Therapy in Postbariatric Lower Body Lift-A Method of Decreasing Postoperative Complications.

BACKGROUND: Lower body lift procedure is one of the most common procedures in postbariatric surgery, which can be followed by postoperative complications that delay the healing time. The purpose of this study was to analyse whether the use of negative pressure wound therapy (NPWT) as a replacement for the classical drainage method would provide better postoperative results with fewer complications. METHODS: The authors reviewed their experience with 46 consecutive patients that underwent lower body lift surgery from 2018 to 2021. They were divided into two groups: 23 of them received NPWT as drainage method and another 23 received classical active drains. We assessed the complication rates and types between the two groups to demonstrate the efficiency of NPWT as a support in the surgical protocol. RESULTS: Forty-six patients were included in this study. Two equal groups formed by 23 patients were analysed for age, sex, type of weight loss, type of circumferential lower body lift, type of drainage, quantity of drainage, time of drain usance, postoperative complications, operation time, hospital stay and frequency of hospital visits. The group that received NPWT had a 26.08% rate of complications as compared with the drain group that had a 47.8% complication rate. CONCLUSIONS: This study is performed as a comparison between negative pressure wound therapy and classical drainage method in lower body lift surgery, as a new method of reducing the postoperative complications. By achieving faster closure of large, undermining areas, it concludes in a lower risk of seroma or hematoma formation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Efficacy and Safety of AbobotulinumtoxinA in Patients with Neurogenic Detrusor Overactivity Incontinence Performing Regular Clean Intermittent Catheterization: Pooled Results from Two Phase 3 Randomized Studies (CONTENT1 and CONTENT2).

BACKGROUND: For patients with neurogenic detrusor overactivity incontinence (NDOI), treatment with oral medications is often unsatisfactory. OBJECTIVE: To assess the efficacy and safety of abobotulinumtoxinA (aboBoNT-A) for NDOI. DESIGN, SETTING, AND PARTICIPANTS: Two randomized, double-blind phase 3 studies (CONTENT1, NCT02660138; CONTENT2, NCT02660359) enrolled patients with NDOI who were regularly performing clean intermittent catheterization (CIC) and were inadequately managed with oral therapy. Pooled results from the first placebo-controlled treatment cycle are reported. INTERVENTION: Patients received injections of aboBoNT-A 600 U (n = 162) or 800 U (n = 161) or placebo (n = 162) into the detrusor muscle. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the mean change from baseline in NDOI episodes per week at week 6. Secondary endpoints reported are the proportion of patients with no NDOI episodes, the volume per void, urodynamic parameters, and quality of life (QoL). Safety was also assessed. Statistical analyses were conducted for the pooled study populations (each aboBoNT-A dose vs placebo). RESULTS AND LIMITATIONS: At week 6, NDOI episodes per week were significantly reduced in each aboBoNT-A group versus placebo (both p < 0.001) and the volume per void had significantly increased. Approximately one-third of patients in each aboBoNT-A dose group reported no NDOI episodes versus 3% of patients in the placebo group. Reductions in urinary incontinence (UI) were reflected in significantly greater improvements in UI-related QoL in the aboBoNT-A groups versus placebo. Urodynamic parameters (bladder capacity and detrusor pressure) were significantly improved with each aboBoNT-A dose versus placebo. Each aboBoNT-A dose was well tolerated. Symptomatic urinary tract infection was the most frequent treatment-emergent adverse event, with incidence comparable across the aboBoNT-A and placebo groups. The studies were terminated prematurely owing to slow recruitment and were not designed for statistical comparison between the two aboBoNT-A doses. CONCLUSIONS: Intradetrusor aboBoNT-A is an effective treatment and alternative option for patients with NDOI who have an inadequate response to oral anticholinergics and are already performing CIC. PATIENT SUMMARY: In patients with bladder muscle overactivity caused by neurological conditions (multiple sclerosis or spinal cord injury) and resulting in urinary incontinence, abobotulinumtoxinA injections improved their symptoms and bladder function, with no unexpected effects.

Management of LUTS in patients with dementia and associated disorders .

AIMS: To systematically review the management of lower urinary tract symptoms (LUTS) in patients with dementia and associated disorders. METHODS: This systematic review was performed according to the PRISMA statement. Studies were identified by electronic search of Embase and Medline databases (last search August 2015) and by screening of reference lists and reviews. RESULTS: Of 1,426 abstracts that were screened, 102 full-text articles were identified and assessed for eligibility. Seventy-six articles were then included in the quantitative synthesis. Urinary incontinence (UI) prevalence rates in dementia patients have varied considerably, ranging from 11 to 93%. In Alzheimer's disease patients, UI usually correlates with disease progression (late-stage dementia). In contrast, LUTS usually precede severe mental failure in Lewy body disease and in vascular dementia. Behavioral therapy, including toilet training and prompted voiding, may be especially useful in patients with unawareness UI. High-quality data to guide the choice of treatment strategies in this population are lacking. Current evidence suggests that antimuscarinics, especially oxybutynin, can be associated with cognitive worsening, due to the blockade of M1 receptors. Thus, the use of antimuscarinics that do not easily cross the blood-brain barrier or are more M2/M3 selective should be considered. No data are available for beta-3 agonists so far. CONCLUSION: Different types of dementia cause different LUTS at varying time points during the disease process and need singular therapeutic approaches. Treatment of LUTS should be tailored to individual patient needs and disease status, considering factors like mobility, cognitive function, and general medical condition. Neurourol. Urodynam. 36:245-252, 2017. © 2015 Wiley Periodicals, Inc.