Histopathologic Analysis of a Recalcitrant Calcaneal Wound Treated Using a Synthetic Hybrid-scale Fiber Matrix.

Traditionally, full-thickness wounds with exposed structures are treated with flap coverage or dermal regenerative templates. Most dermal regenerative templates are biologic in origin, but recently synthetic options have become available. One such product is a synthetic hybrid-scale fiber matrix (SHSFM). In this case, SHSFM was used to treat a recalcitrant calcaneal wound. After the wound granulated, it was biopsied, and histopathologic analysis was conducted. A 16-year-old woman involved in a motor vehicle collision sustained multiple traumatic injuries which were stabilized. Postoperatively, she developed a calcaneal infection and associated wound, which developed into a chronic, nonhealing wound. Failed treatments included removal of hardware, multiple debridements, and advanced wound therapies. An SHSFM was then trialed, which led to granulation of the wound without infection. Despite wound healing, the patient subsequently elected to undergo a below-the-knee amputation due to pain and functional disability from posttraumatic ankle arthritis. The heel was biopsied at the time of amputation for analysis. Pathologists noted excellent granulation tissue formation and complete coverage of the wound surface area and 75% of the wound depth, which included epithelialization and decreasing inflammation at wound edges. Collagen deposition and numerous interspersed blood vessels were present. Foreign material and bacteria were absent. No osteomyelitis was observed. This analysis provided the opportunity to investigate the in vivo regenerate from a novel synthetic SHSFM. Given the uniqueness and challenges presented in this case, the usage of this relatively new product warrants further investigation with larger populations and assorted wound etiologies.

Traumatic jejunal perforation associated with SARS-CoV-2 (COVID-19) infection.

Several case reports have suggested that COVID-19 may increase the risk of gastrointestinal perforation. We report a case of a gastrointestinal perforation developing in a COVID-19 patient who presented due to injuries from a motor vehicle accident. On admission, the patient had elevated white blood cells, with neutrophilia and lymphopenia. Histological examination of tissue surrounding the perforation revealed extensive infiltration of lymphocytes and plasma cells into the intestinal mucosa. These findings are consistent with SARS-CoV-2 infection. However, further pathophysiological studies are needed to assess the mechanisms by which COVID-19 may damage the gastrointestinal mucosa leading to gastrointestinal perforation.

Browning white adipose tissue using adipose stromal cell-targeted resveratrol-loaded nanoparticles for combating obesity.

Enhancing thermogenic energy expenditure via promoting the browning of white adipose tissue (WAT) is a potential therapeutic strategy to manage energy imbalance and the consequent comorbidities associated with excess body weight. Adverse effects and toxicities of currently available methods to induce browning of WAT have retarded exploration of this promising therapeutic approach. Targeted delivery of browning agents to adipose stromal cells (ASCs) in subcutaneous WAT to induce differentiation into beige adipocytes may overcome these barriers. Herein, we report for the first time, ASC-targeted delivery of trans-resveratrol (R), a representative agent, using ligand-coated R-encapsulated nanoparticles (L-Rnano) that selectively bind to glycanation site-deficient decorin receptors on ASCs. After biweekly intravenous administration of L-Rnano to obese C57BL/6 J mice for 5 weeks targeted R delivery significantly induced ASCs differentiation into beige adipocytes, which subsequently resulted in 40% decrease in fat mass, accompanied by improved glucose homeostasis and decreased inflammation. Our results suggest that the ASC-targeted nanoparticle delivery of browning agents could be a transformative technology in combating obesity and its comorbidities with high efficacy and low toxicity.

The anatomy of the peridural membrane of the human spine.

A peridural membranous layer exists between the bony wall of the spinal canal and the dura mater, but reports on the anatomy of this structure have been inconsistent. The objective of this study is to give a precise description of the peridural membrane (PDM) and to define it unambiguously as a distinct and unique anatomical entity. Thirty-four cadaveric sections of human thoraco-lumbar spines were dissected. On gross examination, the PDM appears as a smooth hollow tube that covers the bony wall of the spinal canal. An evagination of this tube into the neural foramen contains the exiting spinal nerve. The entire epidural venous plexus, including its extension into the neural foramina, is contained in the body of the PDM. Histological examination of the PDM shows a variable distribution of veins arteries, lymphatics, and nerves embedded in a continuous sheath of fibrous, areolar, and adipose tissue. The posterior longitudinal ligament may be considered a dense condensation of fibrous tissue within the membrane. Thus, the PDM is a unique, continuous, and complete anatomical structure. In the spinal canal, the PDM is adjacent to the periosteum. In the neural foramen, suprapedicular PDM and pedicular periosteum separate anatomically to form a suprapedicular compartment, bounded anteriorly by the intervertebral disc and posteriorly by the facet joint. Trauma or degeneration of the disc or facet joint may lead to inflammation and pain sensitization of PDM. This protective mechanism may be of considerable importance for the functioning of the spine under conditions of strain.

The peridural membrane of the spine has characteristics of synovium.

The peridural membrane (PDM) is a well-defined structure between dura mater and the wall of the spinal canal. The spine may be viewed as a multi-segmented joint, with the epidural cavity and neural foramina as joint spaces and PDM as synovial lining. The objective of this investigation was to determine if PDM has histological characteristics of synovium. Samples of the PDM of the thoraco-lumbar spine were taken from 23 human cadavers and analyzed with conventional light microscopy and confocal microscopy. Results were compared to reports on similar analyses of synovium in the literature. Histological distribution of areolar, fibrous, and adipose connective tissue in PDM was similar to synovium. The PDM has an intima and sub-intima. No basement membrane was identified. CD68, a marker for macrophage-like-synoviocytes, and CD55, a marker for fibroblast-like synoviocytes, were seen in the lining and sub-lining of the PDM. Multifunctional hyaluronan receptor CD44 and hyaluronic acid synthetase 2 marker HAS2 were abundantly present throughout the membrane. Marked presence of CD44, CD55, and HAS2 in the well-developed tunica muscularis of blood vessels and in the body of the PDM suggests a role in the maintenance and lubrication of the epidural cavity and neural foramina. Presence of CD68, CD55, and CD44 suggests a scavenging function and a role in the inflammatory response to noxious stimuli. Thus, the human PDM has histological and immunohistochemical characteristics of synovium. This suggests that the PDM may be important for the homeostasis of the flexible spine and the neural structures it contains.

Spinal Coccidioidomycosis: A Complication From Medication Noncompliance.

Spinal coccidioidomycosis is a rare disseminated form of coccidioidomycosis infection. According to the literature, majority of patients are African American males. We present a rare case of spinal coccidioidomycosis in a young, Caucasian female with coccidioidomycosis meningitis at age 16 years who presented with bilateral lower extremity weakness after antifungal medication lapse for one year. Imaging revealed cystic arachnoid formations along her thoracic spine. Pathology report confirmed spinal arachnoiditis with coccidioidomycosis. This case report details a rare incidence of spinal coccidioidomycosis and reviews previous literature.

Extrapulmonary sarcoidosis in an atypical patient demographic.

Although it typically presents with cough and dyspnea due to pulmonary involvement, sarcoidosis is a multisystem granulomatous disease and therefore may present with extrapulmonary manifestations. Cutaneous manifestations are common, while hepatic sarcoidosis is uncommon and osseous manifestations are exceedingly rare. This article describes osseous, hepatic, and cutaneous manifestations due to sarcoidosis. The patient was diagnosed with sarcoidosis, treated with a dynamic hip screw implant with a derotational screw, and discharged on a new medication regimen: vitamin D, calcium supplements, alendronate, methotrexate, and hydroxychloroquine.

Pure Squamous Cell Carcinoma of the Gallbladder Masquerading as a Hepatic Mass.

Gallbladder (GB) carcinomas are adenocarcinomas (AC) in the majority of cases. Adenosquamous carcinoma (ASC) and pure squamous cell carcinoma (SCC) of the gallbladder are rarely encountered and comprise 1-3% of gallbladder cancer cases.  Pure squamous cell carcinoma of the gallbladder is rarer with less than 1% of the incidence. Most of the published literature is based on case reports and case series. The survival rates of ASC and SCC of the gallbladder are significantly lower (mean of five months) compared to the AC of the gallbladder (mean survival of 11.4 months). Most of these lesions are advanced at presentation, rendering them unresectable and resulting in a poor prognosis. However, if the lesions are diagnosed at an early stage, they could potentially be resectable. We report one such rare case of pure SCC GB presenting as a hepatic mass. The patient subsequently underwent resection of the gallbladder and liver mass with complete recovery and is currently planned for chemotherapy and radiation treatment.

Primary esophageal diffuse large B cell lymphoma presenting with tracheoesophageal fistula: A rare case and review.

Primary non-Hodgkin lymphomas in the esophagus are rare. Tracheoesophageal fistulas mainly arise from solid esophageal carcinoma or mediastinal malignancies. Our patient presented with cough, dysphagia and weight loss, and upon initial computed tomography imaging and esophagogastroduodenoscopy, a malignant mass in the middle third of esophagus with tracheoesophageal fistula was found. The location of the mass and presence of malignant tracheoesophageal fistula were strongly suggestive of squamous cell carcinoma. However, tumor biopsy revealed diffuse large B-cell lymphoma. This case report details a rare incident of a primary diffuse large B-cell lymphoma presented as tracheoesophageal fistula and reviews previous literature.

The Peridural Membrane of the Human Spine is Well Innervated.

There is evidence that low back pain may originate from a peridural membrane (PDM) at the inferior and medial aspect of neural foramen of the lumbar spine. The objective of this investigation was to determine if this membrane contains neural elements suggestive of sensory innervation with nociceptive function. Spines of four embalmed and three non-embalmed human cadavers were dissected using a sagittal approach to the neural foramen. Seventeen samples of the peridural membrane overlying the neural foramen were collected for immunohistochemistry (IHC) examination by light microscopy and transmission electron microscopy (TEM). Chromagin tagged antibodies to protein gene product 9.5 (PGP9.5) and S-100, and fluorescent antibodies to substance P and calcitonin gene related peptide (CGRP) were used to label neural structures in tissue sections cut from paraffin embedded blocks. This approach allows good visualization of all neural elements, small sensory, and nociceptive nerve fibers in particular. Neural elements were found in all samples. Marked presence of small nerve fibers was observed in 12 of 15 samples. IHC and TEM evaluation revealed myelinated as well as unmyelinated fibers in the peridural membrane. CGRP and substance P immunoreactive fibers indicative of nociceptive function were abundant. These findings confirm and expand evidence that the peridural membrane in human is well innervated and contains sensory nociceptive nerve fibers suggestive of a nociceptive function of the membrane.

Carcinoma of the lungs causing enlarged kidneys.

Bilateral enlarged kidneys can be caused by a number of conditions. Renal metastasis is included in the differential diagnosis. We report a case of a 67-year-old woman with a 6-month history of productive cough and unintentional weight loss. Cavitary pulmonary lesions and bilateral enlarged kidneys were noted on imaging studies. Hematuria, azotemia, and proteinuria were present. Renal biopsy showed squamous carcinoma cells invading normal-appearing glomeruli and atrophic tubules. The invasive squamous cells stained negative for CK7 and CK 20. Lung biopsy confirmed squamous cell carcinoma. Our case shows that in patients with renal enlargement, even with the absence of a focal mass, renal metastasis should be considered, especially in those with suspected or diagnosed malignancy elsewhere.

Solitary fibrous tumor of the orbit with epithelioid features.

Extrapleural solitary fibrous tumors have often been confused with other mesenchymal tumors, such as hemangiopericytoma, fibrous histiocytoma, fibrous meningioma, and leiomyoma, because of morphologic similarity and underrecognition, especially if some unusual features are present. Recently, epithelioid solitary fibrous tumor has been reported in the mediastinum. We report a case of solitary fibrous tumor of the orbit with biphasic architecture, including spindle cell and epithelioid components. Both components demonstrated immunohistochemical features of a solitary fibrous tumor. A background of scattered vessels was present. No evidence of significant nuclear atypia or mitotic activity was noted. In this report, we discuss the differential diagnosis of solitary fibrous tumor with unusual epithelioid features. Extrapleural solitary fibrous tumor should be included in the differential diagnosis of tumors of the orbit with a spindle cell appearance even in the presence of some epithelioid morphology.

Common causes of troponin elevations in the absence of acute myocardial infarction: incidence and clinical significance.

Cardiac troponin is a preferred biomarker of acute myocardial infarction (MI). Unfortunately, elevation of troponin can be detected in a variety of conditions other than acute MI. This review focuses on the incidence and clinical significance of increased troponin in conditions commonly associated with troponin elevations, particularly in those that may resemble acute MI.

Diagnosis of invasive septate mold infections. A correlation of microbiological culture and histologic or cytologic examination.

We correlated results of microbiologic culture and histopathologic examination for 2,891 consecutive samples from autopsy tissue, surgical or biopsy tissue, and bronchoalveolar lavage (BAL) or bronchial washing (BW) specimens. For 23 autopsy cases with suspected invasive septate mold infections by histopathologic examination, culture yielded a mold in 12 cases (52%). For 1,683 surgical or biopsy samples, histopathologic evidence of invasive septate mold infection was present in 30 samples, 9 of which also grew mold by culture (30%); 20 additional samples grew mold in culture alone, possibly representing culture contamination. Of 1,185 BAL and BW samples, mold was evident in 28 by cytologic examination and culture, 20 by cytologic examination alone, and 68 by culture alone. These results suggest a positive concordance for culture and histologic-cytologic examination of 23%, although both methods were negative in 96% of surgical and biopsy tissue and BAL and BW samples. The septate molds cultured from these samples were Aspergillus fumigatus (19), Aspergillus flavus (15), Aspergillus terreus (13), Aspergillus niger (7), Fusarium species (3), and Scedosporium apiospermum (2). A flavus was isolated significantly more frequently from tissue than from BAL and BW samples.