Title Transgelin-2 in Multiple Myeloma: A New Marker of Renal Impairment?

Transgelin is a 22-kDa protein involved in cytoskeletal organization and expressed in smooth muscle tissue. According to animal studies, it is a potential mediator of kidney injury and fibrosis, and moreover, its role in tumorigenesis is emerging in a variety of cancers. The study included 126 ambulatory patients with multiple myeloma (MM). Serum transgelin-2 concentrations were measured by enzyme-linked immunoassay. We evaluated associations between baseline transgelin and kidney function (serum creatinine, estimated glomerular filtration rate—eGFR, urinary markers of tubular injury: cystatin-C, neutrophil gelatinase associated lipocalin—NGAL monomer, cell cycle arrest biomarkers IGFBP-7 and TIMP-2) and markers of MM burden. Baseline serum transgelin was also evaluated as a predictor of kidney function after a follow-up of 27 months from the start of the study. Significant correlations were detected between serum transgelin-2 and serum creatinine (R = 0.29; p = 0.001) and eGFR (R = −0.25; p = 0.007). Transgelin significantly correlated with serum free light chains lambda (R = 0.18; p = 0.047) and serum periostin (R = −0.22; p = 0.013), after exclusion of smoldering MM patients. Patients with decreasing eGFR had higher transgelin levels (median 106.6 versus 83.9 ng/mL), although the difference was marginally significant (p = 0.05). However, baseline transgelin positively correlated with serum creatinine after the follow-up period (R = 0.37; p < 0.001) and negatively correlated with eGFR after the follow-up period (R = −0.33; p < 0.001). Moreover, higher baseline serum transgelin (beta = −0.11 ± 0.05; p = 0.032) significantly predicted lower eGFR values after the follow-up period, irrespective of baseline eGFR and follow-up duration. Our study shows for the first time that elevated serum transgelin is negatively associated with glomerular filtration in MM and predicts a decline in renal function over long-term follow-up.

Morphological prerequisites for the formation of fascial duplication in the elimination of damage to the anterior rectal wall during prostatectomy

Background Intraoperative rectal injury in prostatectomy patients is an uncommon but severe complication. Particular attention is paid to improving the results of healing damage to the anterior rectal wall during prostatectomy.Objective To study the morphological features of the parietal pelvic fascia and the rectal wall to substantiate the possibility of the formation of fascial duplication in the elimination of damage to the anterior rectal wall during prostatectomy.Material and Methods The authors carried out an intravital morphological analysis of the parietal pelvic fascia covering the levator rectum muscle and the anterior rectal wall in 10 men.Results The parietal pelvic fascia contains more powerful bundles of collagen fibers, which in certain areas are partially woven into the fibers of striated muscle tissue. The adventitia of the rectum is characterized by a looser arrangement of the interacting components of the formed connective and smooth muscle tissue. In the studied formations of the small pelvis, the thickness of collagen fibers separately and in the composition of bundles, as well as the cells of the differon and each fiber separately did not differ, which indicated the identity of their tinctorial properties in the compared zones.Conclusion Morphological analysis showed that when juxtaposing and touching the edges of the healing area of the surgical wound without tension, a stable and continuous scar of the fascial duplication is formed, which ensures reliable fusion of the stitched anatomical structures.

Gastric Adenomyoma: Salient Imitator

Introduction/Objective Gastric adenomyoma is a lesion characterized by proliferation of epithelium and smooth muscle in the stomach or small bowel. By ultrasound, gastric adenomyoma usually appears as a submucosal nodule with a cystic center. They can mimic many benign and malignant conditions and are an important differential diagnosis to consider in fine needle aspiration of submucosal upper gastrointestinal lesions. Methods/Case Report We present a 30-year-old male who presented with abdominal pain, dyspepsia, and heartburn. Esophagogastroduodenoscopy demonstrated a 10 mm well-circumscribed hypoechoic mass in the antral submucosa along the greater curvature of the stomach. Two years later, the lesion was 18.6 mm in greatest dimension and fine needle aspiration was performed. Cell block showed foci of benign gastric glands and bland smooth muscle tissue, positive for smooth muscle actin and desmin, and negative for CD34 and c-kit (CD117). Gastrointestinal stromal tumor was the main differential diagnosis and adenomyosis was not considered, thus, the biopsy was thought to represent normal gastric wall, and the glands were dismissed as contaminant from the aspiration. A subsequent ultrasound two years later again demonstrated the lesion, now 21.5 mm in greatest dimension, and definitive resection was performed. Histologic examination showed a segment of stomach with gastric antral-type mucosa and an underlying mass forming lesion consisting of scattered gastric type glands admixed with smooth muscle bundles, consistent with gastric adenomyoma. The glands were completely surrounded by smooth muscle and lamina propria. Our patient has been asyptomatic one year since resection of the gastric adenomyoma. Results (if a Case Study enter NA) NA Conclusion Gastric adenomyoma is an important differential of intramural spindle cell neoplasms of the gastrointestinal tract alongside many benign and malignant conditions. Consideration of gastric adenomyoma at the time of the original biopsy would have spared the patient uncertainty regarding their prognosis and allowed for definitive resection two years earlier.

Design and Characterization of Maltose-Conjugated Polycaprolactone Nanofibrous Scaffolds for Uterine Tissue Engineering

Purpose Uterine anomalies are prevalent in women, and the major treatment assisted to them is hysterectomy as donor availability is extremely low. To overcome this, engineering uterine myometrium smooth muscle tissue has become very important. Several studies have shown that polycaprolactone (PCL) nanofibers are very effective in engineering smooth muscles, as this type of scaffold has structural similarities to the extracellular matrices of the cells. Here, we hypothesize that by electrospinning PCL nanofibers, they form a suitable scaffold for uterine tissue engineering. Methods Polycaprolactone nanofibrous scaffolds were fabricated, and surface modification was performed following two step wet chemistry method. First step is aminolysis which introduces the primary amine groups on the PCL scaffolds following which maltose is conjugated on the scaffolds. This was confirmed by the ninhydrin assay for the presence of amine groups. This was followed by ELLA assay where the presence of maltose on the scaffold was quantified. Modified scaffolds were further characterized by scanning electron microscope (SEM), contact angle analysis and Fourier transform infrared spectroscopy (FTIR). MTT assay, live-dead assay and actin staining were performed on the maltose immobilization to study the improvement of the cell attachment and proliferation rates on the modified scaffolds. Results Human uterine fibroblast (HUF) cells displayed significant proliferation on the maltose-modified PCL scaffolds, and they also exhibited appropriate morphology indicating that these modified fibers are highly suitable for uterine cell growth. Conclusion Our results indicate that the fabricated maltose PCL (MPCL) scaffolds would be a potential biomaterial to treat uterine injuries and promote regeneration. Lay Summary and Future Work Uterine anomalies are prevalent in women, and the major treatment is hysterectomy as donor availability is extremely low. Over the past few years, considerable efforts have been directed towards uterine tissue regeneration. This study is to design a tissue engineered scaffold that could act as a human uterine myometrial patch. We propose to create uterine fibroblast-based synthetic scaffolds that act in a condition similar to the intrauterine microenvironment where the embryos are embedded in the uterine wall. For understanding of the efficiency of the myometrial patch, functional characterization will be performed to study the effects of estrogen and prostaglandins on myometrial activity of the designed patch. Results from these experiments will assist a deeper understanding of how to construct a total bioengineered uterus which can substitute the uterus transplantation procedure, which nonetheless is in its initial stages of development. Graphical Abstract

RNA Sequencing for Personalized Treatment of Metastatic Leiomyosarcoma: Case Report

Uterine leiomyosarcoma (UL) is a rare malignant tumor that develops from the uterine smooth muscle tissue. Due to the low frequency and lack of sufficient data from clinical trials there is currently no effective treatment that is routinely accepted for UL. Here we report a case of a 65-years-old female patient with metastatic UL, who progressed on ifosfamide and doxorubicin therapy and developed severe hypertensive crisis after administration of second line pazopanib, which lead to treatment termination. Rapid progression of the tumor stressed the need for the alternative treatment options. We performed RNA sequencing and whole exome sequencing profiling of the patient’s biopsy and applied Oncobox bioinformatic algorithm to prioritize targeted therapeutics. No clinically relevant mutations associated with drug efficiencies were found, but the Oncobox transcriptome analysis predicted regorafenib as the most effective targeted treatment option. Regorafenib administration resulted in a complete metabolic response which lasted for 10 months. In addition, RNA sequencing analysis revealed a novel cancer fusion transcript of YWHAE gene with fusion partner JAZF1. Several chimeric transcripts for YWHAE and JAZF1 genes were previously found in uterine neoplasms and some of them were associated with tumor prognosis. However, their combination was detected in this study for the first time. Taken together, these findings evidence that RNA sequencing may complement analysis of clinically relevant mutations and enhance management of oncological patients by suggesting putative treatment options.

Histopathological Evaluation of A Tissue Fragment Obtained In Conjunctivo-Müllerectomy Surgery

Purpose To evaluate striated skeletal muscle fibers (upper eyelid levator muscle) in specimens taken from conjunctivo-müllerectomy surgery and correlate the surgical response of elevation greater than 2 mm in this surgery. Methods Histopathological analysis of 20 excised conjunctivo-müllerectomy fragments for treating involutional ptosis of any magnitude with a 10% positive and satisfactory phenylephrine test to check for skeletal muscle fibers. Results All analyzed tissue samples only had conjunctiva and smooth muscle tissue. We attest to the absence of striated muscle fibers in these samples. Conclusion There are no upper eyelid levator muscle fibers in the excised tissue in conjunctivo-müllerectomy surgery. The surgical response of elevation greater than 2 mm in this surgery may only be due to the closeness of the upper eyelid levator muscle to the superior border of the tarsal plate.

Case Report: Multiple Cavernous Pericardial Lymphangioma (Pericardial Lymphangiomatosis) in a Captive Peregrine Falcon (Falco peregrinus brookei)

A 12-year-old female peregrine falcon (Falco peregrinus brookei) from a private raptor breeding facility that presented a good body condition, died suddenly without showing previous symptoms. At necropsy, in the coelomic cavity, multiple cystic structures demarcated by a thin transparent wall and filled with a serous content were observed. They were firmly adhered to the cranial part of the epicardium and adjacent tissues and occupied the entire thoracic area of the coelomic cavity. Microscopically, emerging simultaneously from several areas the epicardium, multiple irregular channels and cystic spaces, lined by a single endothelial cell layer and separated by fibrovascular septa containing smooth muscle tissue, were observed. Immunohistochemical examination revealed that the neoplastic endothelial cells positively immunolabelled for the pan-endothelial marker factor VIII-related antigen but immunostained negative for cytokeratins (PCK26) while strong positivity for sarcomeric α-smooth muscle actin (α-SMA) was detected in the cystic walls. Based on the morphological and immunohistochemical findings, lesions were determined as consistent with a multiple cavernous pericardial lymphangioma, or pericardial lymphangiomatosis, a rare vascular neoplasm. The animal also showed a diffuse chronic perihepatitis, a necrotic area in the liver and foci of cartilaginous metaplasia and calcification in the aorta and vena cava. Literature review, particularly on the epidemiology of lymphangioma, demonstrated the rarity of this tumor in the different animal species and in this location, particularly in birds, being the first report of this type of tumor in a peregrine falcon.

Three unusual Pulmonary fibroleiomyomatous hamartomas: cases report and literature review

BackgroundPulmonary fibroleiomyomatous hamartomas (PFLH) is an extremely rare benign leision, characterized by most patients have no respiratory symptoms and pulmonary nodules is found during rutine chest imaging. It’s completely different from fibrochondrolipoma (ie.chondrogenic pulmonary hamartoma, FCL), Herein, we report three unusual cases of PFLH in a 48-year-old male patient, a 63-year-old male patient and a 63-year-old female patient,respectively and discuss their morphological characteristics and differential diagnoses including fibrochondrolipoma (FCL), pulmonary fibroadenoma (PFA), primary pulmonary leiomyoma (PPL), bronchioloalveolar adenoma (BAA), solitary fibrous tumor (SFT) and pulmonary metastatic leiomyoma (PML) in female patients.Case presentationThree cases showed singler and multiple nodules in the pulmonary parenchyma,the boundary of these nodules was clear. it showed swelling growth and lobulated in larger tumors. it consisted of the mesenchymal rich in spindle cells and the glandular epithelium tissue. the spindle cells form smooth muscle tissue and fibrous tissue, the glandular epithelium with invagination showed glandular ducts or fissures, disorder of composition. Immunohistochemical staining showed Desmin, SMA,H-caldesmon-positive in the all spindle cells; H-caldesmon-positive, SMA-weak positive and desmin-negative in the long spindle cells; TTF-1,CK7 were positive in glandular epithelium and P63,CK5/6 were expressed in basal cells; HMB45,S-100,CD34, ER,PR were negative in all cells. Additionally, Ki-67 VPI was low and less than 1%. The immunohistochemical analysis combined with the morphological results supported the diagnosis of solitary PFLH (SPFLH) or multiple PFLH (M PFLH). There was no recurrence in SPFLH and recurrence in MFLH in the group.ConclusionsPFLH is a rare benign leision .It originated from the small bronchus or smooth muscle cells of vascular wall which implanted into the lung parenchyma and overgrowth into nodules or mass, the messenchymal component of PFLH is the most important for accurate pathological diagnosis, PFLH is easy to be confused with PFA and PPL when there are not enough immune marker such as SMA,desmin, H-caldesmon to mark the mesenchymal components. Therefore, Diagnosis of PFLH mainly depends on pathological examination, females patients have to exclude PML.

QUANTITATIVE PARAMETERS AND MORPHOLOGICAL CHARACTERISTICS OF THE UTERINE TUBES AMPULLAE IN THE FIRST PERIOD OF ADULTHOOD

The study of the age-related anatomical variability, its exact morphological characteristics in adulthood, established using modern research methods, are needed, which can serve as a criterion for a conditional norm. The aim of the study is to determine the macro- and micro-morphometric parameters of the ampulla of the fallopian tubes of women in the first period of adulthood using prosection material and their morphological characteristics. The ampulla of both fallopian tubes of 44 nulliparous and 58 giving birth women of the first period of adulthood (from 21 to 35 years) were examined. Organometric, histological, immunohistochemical and macro- and micro-morphometric research methods were used. It determined the length of the ampoules, their outer diameter at the junction of the isthmus in the ampoule, in the central part of the ampoule and at the junction of the ampoule in the funnel. Histological sections were stained with hematoxylin and eosin, picro fuchsin according to van Gieson. In the immunohistochemical study of the samples, antibodies against vimentin and the CD68 marker were used. The area of ​​the lumen of the ampulla of the fallopian tube and the area of ​​its wall was calculated, and the circumference of the epithelial lining was measured. As a result, it was found that the outer diameter of the fallopian tubes at the junction of the isthmus into the ampulla and the ampoule into the funnel, as well as in the central part of the ampoule, is characterized by the absence of a statistically significant difference in parameters in nulliparous and giving birth women. The histological picture of the ampulla of the fallopian tubes both in nulliparous and in women giving birth in the first period of adulthood is of the same type and is represented by a mucous membrane that forms many thin papillary folds, internal circular and external longitudinal layers of smooth muscle tissue of the muscular membrane and the serous membrane. The detection in the tissues of the ampulla of the fallopian tubes in nulliparous and giving birth women in a moderate amount of CD68-immunopositive macrophages, the concentration of which increases in the epithelium and near it, as well as the expression of vimentin in the vessel walls and individual fibroblasts, indicates the presence of physiological tissue regeneration processes. Analysis of the indicators of the areas of the lumen of the ampoule and its wall at the median section, as well as the circumference of the epithelial lining, allows us to conclude that these parameters predominate in the right fallopian tube.