Primary Intracranial Ewing Sarcoma With an Unusual Presentation: A Case Report.

Primary extraosseous intracranial Ewing sarcoma (ES) is an extremely rare disease, limited to the pediatric population, that primarily originates in the skull. Here, we present an unusual case of adult Ewing's sarcoma originating from the brain parenchyma. The 50-year-old male patient visited our hospital with severe headache lasting 3 weeks. MRI presented 6.1×6.2×5.2 cm sized heterogeneously enhanced mass containing peritumoral edema in the right frontal lobe. The patient underwent right frontal craniotomy, at which time the gray and red masses adhered to the surrounding brain parenchyma. The mass was completely resected using neuronavigation and electrophysiological monitoring. Histopathological examination revealed ES-compatible findings of small round cell tumor and CD-99 positive membranous immunostaining. Next generation sequencing revealed translocation and fusion of EWSR1 and FLI1, consistent with a confirmed diagnosis of ES. Consequently, the patient underwent postoperative radiotherapy. The present case revealed adult primary intracranial ES arising from the frontal lobe. Although its etiology remains poorly understood, intraparenchymal ES should be included in the differential diagnosis of parenchymal brain tumors.

A Rare Atypical Case of Asymptomatic and Spontaneous Intraneural Hematoma of Sural Nerve: A Case Report and Literature Review.

Intraneural hematoma is a rare disease that results in an impaired nerve function because of bleeding around the peripheral nerve, with only 20 cases reported. Trauma, neoplasm, and bleeding disorders are known factors for intraneural hematoma. However, here we report atypical features of asymptomatic and spontaneous intraneural hematoma which are difficult to diagnose. A 60-year-old woman visited our clinic with the complaint of a palpable mass on the right calf. She reported no medical history or trauma to the right calf and laboratory findings showed normal coagulopathy. Ultrasonography was performed, which indicated hematoma near saphenous vein and sural nerve or neurogenic tumor. We performed surgical exploration and intraneural hematoma was confirmed on sural nerve. Meticulous paraneuriotomy and evacuation was performed without nerve injury. Histological examination revealed intraneural hematoma with a vascular wall. No neurologic symptoms were observed. In literature review, we acknowledge that understanding anatomy of nerve, using ultrasonography as a diagnostic tool and surgical decompression is key for intraneural hematoma. Our case report may help establish the implications of diagnosis and treatment. Also, we suggested surgical treatment is necessary even in cases that do not present symptoms because neurological symptoms and associated symptoms may occur later.

A prospective multicenter assessor blinded pilot study using confocal laser endomicroscopy for intraoperative brain tumor diagnosis.

In this multi-center, assessor-blinded pilot study, the diagnostic efficacy of cCeLL-Ex vivo, a second-generation confocal laser endomicroscopy (CLE), was compared against the gold standard frozen section analysis for intraoperative brain tumor diagnosis. The study was conducted across three tertiary medical institutions in the Republic of Korea. Biopsy samples from newly diagnosed brain tumor patients were categorized based on location and divided for permanent section analysis, frozen section analysis, and cCeLL-Ex vivo imaging. Of the 74 samples from 55 patients, the majority were from the tumor core (74.3%). cCeLL-Ex vivo exhibited a relatively higher diagnostic accuracy (89.2%) than frozen section analysis (86.5%), with both methods showing a sensitivity of 92.2%. cCeLL-Ex vivo also demonstrated higher specificity (70% vs. 50%), positive predictive value (PPV) (95.2% vs. 92.2%), and negative predictive value (NPV) (58.3% vs. 50%). Furthermore, the time from sample preparation to diagnosis was notably shorter with cCeLL-Ex vivo (13 min 17 s) compared to frozen section analysis (28 min 28 s) (p-value < 0.005). These findings underscore cCeLL-Ex vivo's potential as a supplementary tool for intraoperative brain tumor diagnosis, with future studies anticipated to further validate its clinical utility.

Effective wound healing on diabetic mice by adhesive antibacterial GNPs-lysine composited hydrogel.

Current trends in wound care research focus on creating dressings for diverse wound types, aiming to effectively control the wound healing process. We proposed a wound dressing composed of oxidized hyaluronic acid and amine gelatin with embedded lysine-modified gelatin nanoparticles (HGel-GNPs-lysine). This dressing improves mechanical properties and reduces degradation rates. The storage modulus for HGel-GNPs-lysine was 3,800 Pa, exceeding that of HGel (1,750 Pa). The positively charged surface of GNPs-lysine effectively eliminated Escherichia coli and Staphylococcus aureus. In a diabetic mice model (C57BL/6), HGel-GNPs-lysine immobilized with basic-fibroblast growth factor promoted granulation tissue thickness and collagen density. Gene expression analysis indicated that HGel-GNPs-lysine reduced inflammation and enhanced angiogenesis. This study highlights that HGel-GNPs-lysine could offer alternative treatment strategies for regulating the inflammatory response at the injury site in wound dressing applications.

Corrigendum: Clinical feasibility of miniaturized Lissajous scanning confocal laser endomicroscopy for indocyanine green-enhanced brain tumor diagnosis.

[This corrects the article DOI: 10.3389/fonc.2022.994054.].

Recurrence of Rathke's Cleft Cyst Following Surgery and Histopathological Considerations for Recurrence: A Case Presentation.

Recurrence of Rathke's cleft cysts (RCC) following surgery is not uncommon. We present a 33-year-old male patient with chronic headache and visual disturbances whose MRI showed mostly cystic, suprasellar mass with peripheral enhancement. Endoscopic extended transsphenoidal approach and tumor resection was performed and RCC was pathologically confirmed postoperatively. Early recurrence was first suspected at 3 months following surgery, and his serial MRIs showed a recurred mass without associated clinical symptoms. Upon further histopathological study, extensive squamous metaplasia and high Ki-67 were seen. Also, in this study, we discuss important factors associated with cyst recurrence following surgery.

Rare Case of Managing and Evaluating Viability after Replantation of a Serial Self-Amputated Bilateral Testis by a Patient with Schizophrenia: A Case Report.

Amputation of the testis is very rare in clinical situations; therefore, most surgeons have no experience with an amputated testis. In this case, a 31-year-old male with schizophrenia amputated both testes due to self-mutilation. We performed replantation surgery via microscopy. On postoperative day 1, he removed his right testis by using his hand, even though his hands were restrained. The second attack disrupted the viability of the right testis. However, after proper management, we checked the normal sex hormone level by preserving the replanted left testis. We evaluated the viability of the replanted testis by performing five examinations, namely, intraoperative indocyanine green injection, testicular scan with technetium pertechnetate, contrast-enhanced computerized tomography, Doppler ultrasonography, and serum testosterone level. In this report, we aimed to describe our rare experience about management with replantation of the amputated testes and evaluation of their viability.

CXCR4 Targeting Nanoplatform for Transcriptional Activation of Latent HIV-1 Infected T Cells.

Antiretroviral drugs are limited in their ability to target latent retroviral reservoirs in CD4+ T cells, highlighting the need for a T cell-targeted drug delivery system that activates the transcription of inactivated viral DNA in infected cells. Histone deacetylase inhibitors (HDACi) disrupt chromatin-mediated silencing of the viral genome and are explored in HIV latency reversal. But single drug formulations of HDACi are insufficient to elicit therapeutic efficacy, warranting combination therapy. Furthermore, protein kinase C activators (PKC) have shown latency reversal activity in HIV by activating the NF-κB signaling pathway. Combining HDACi (SAHA) with PKC (PMA) activators enhances HIV reservoir activation by promoting chromatin decondensation and subsequent transcriptional activation. In this study, we developed a mixed nanomicelle (PD-CR4) drug delivery system for simultaneous targeting of HIV-infected CD4+ T cells with two drugs, suberoylanilide hydroxamic acid (SAHA) and phorbol 12-myristate 13-acetate (PMA). SAHA is a HDACi that promotes chromatin decondensation, while PMA is a PKC agonist that enhances transcriptional activation. The physicochemical properties of the formulated PD-CR4 nanoparticles were characterized by NMR, CMC, DLS, and TEM analyses. Further, we investigated in vitro safety profiles, targeting efficacy, and transcriptional activation of inactivated HIV reservoir cells. Our results suggest that we successfully prepared a targeted PD system with dual drug loading. We have compared latency reversal efficacy of a single drug nanoformulation and combination drug nanoformulation. Final PD-SP-CR4 successfully activated infected CD4+ T cell reservoirs and showed enhanced antigen release from HIV reservoir T cells, compared with the single drug treatment group as expected. To summarize, our data shows PD-SP-CR4 has potential T cell targeting efficiency and efficiently activated dormant CD4+ T cells. Our data indicate that a dual drug-loaded particle has better therapeutic efficacy than a single loaded particle as expected. Hence, PD-CR4 can be further explored for HIV therapeutic drug delivery studies.

Targeted and efficient delivery of rifampicin to macrophages involved in non-tuberculous mycobacterial infection via mannosylated solid lipid nanoparticles.

Non-tuberculous mycobacterial infections are representative difficult-to-cure lung diseases with high incidence. Conventional treatments have several limitations such as negative side effects and increased drug resistance due to long-term administration. To overcome these limitations, there is a growing need for more stable drug delivery systems. Among the various drug delivery platforms developed thus far, solid lipid nanoparticles can be effectively loaded with hydrophobic substances and their physicochemical properties can be easily manipulated through surface modification, which makes them highly suitable drug delivery materials. Recent studies have reported the successful development of nanoparticles capable of selectively delivering drugs by targeting lectin-like receptors overexpressed on the surface of immune cells. Among these lectin-like receptors, the mannose receptor is a promising target because it is expressed on the surface of macrophages and is involved in immune activity. This study sought to synthesize rifampicin-loaded mannose surface-modified solid lipid nanoparticles (Man-RIF SLNs). The Man-RIF SLN synthesis process was first optimized, after which the characteristics of the synthesized particles were analyzed using dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). The surface modification with mannose was confirmed through FT-IR analysis. More importantly, the synthesized Man-RIF SLNs exhibited antibacterial and anti-biofilm properties against Mycobacterium intracellulare, a causative agent of non-tuberculous lung disease. Therefore, this study demonstrated that mannose receptor-targeted rifampicin delivery through solid lipid nanoparticles can be effectively applied to the treatment of non-tuberculous lung disease. Moreover, Man-RIF SLNs could also be used for the targeted delivery of drugs to several types of carcinoma cells or immune cells, as well as to treat lung diseases.

Liquid-Metal Core-Shell Particles Coated with Folate and Phospholipids for Targeted Drug Delivery and Photothermal Treatment of Cancer Cells.

Recently, several methods have been used for cancer treatment. Among them, chemotherapy is generally used, but general anticancer drugs may affect normal cells and tissues, causing various side effects. To reduce the side effects and increase the efficacy of anticancer drugs, a folate-based liquid-metal drug nanodelivery system was used to target the folate receptor, which is highly expressed in cancer cells. A phospholipid-based surface coating was formed on the surface of liquid-metal nanoparticles to increase their stability, and doxorubicin was loaded as a drug delivery system. Folate on the lipid shell surface increased the efficiency of targeting cancer cells. The photothermal properties of liquid metal were confirmed by near-infrared (NIR) laser irradiation. After treating cancerous and normal cells with liquid-metal particles and NIR irradiation, the particles were specifically bound to cancer cells for drug uptake, confirming photothermal therapy as a drug delivery system that is expected to induce cancer cell death through comprehensive effects such as vascular embolization in addition to targeting cancer cells.

The significance of decompressive craniectomy for older patients with traumatic brain injury: a propensity score matching analysis from large multi-center data.

The efficacy of decompressive craniectomy (DC) for traumatic brain injury (TBI) have been investigated in two recent randomized clinical trials (RCTs) and DC is recommended as an optional treatment for improving overall survival compared to medical treatment. However, the two RCTs enrolled extremely young adults, and the efficacy of DC in older adults remains questionable. Therefore, to identify the efficacy of DC in older adults, we compared patients who received medical care with those who underwent DC after propensity score matching (PSM). From the Korea Multi-center Traumatic Brain Injury Database, 443 patients identified as having intracranial hypertension and a necessity of DC were retrospectively enrolled. The patients were classified into the DC (n = 375) and non-DC (n = 68) groups according to operation records. The PSM was conducted to match the patients in the DC group with those receiving medical care (non-DC). After PSM, the newly matched group (DC, n = 126) was compared with patients without DC (non-DC, n = 63). The mean difference in the logit of the propensity scores (LPS) was 0.00391 and the mean age of enrolled patients were 65 years. The results of the comparative analyses after PSM showed that the 6-month mortality rate of the non-DC group was higher than that of the DC group (61.9% vs. 51.6%, p = 0.179). In terms of favorable outcomes (modified Rankin Scale [mRS] score < 4), the DC group showed a lower rate of favorable mRS scores (11.9% vs. 17.5%, p = 0.296) than the non-DC group.

One-Pot Synthesis of Double-Network PEG/Collagen Hydrogel for Enhanced Adipogenic Differentiation and Retrieval of Adipose-Derived Stem Cells.

Hydrogels are widely used in stem cell therapy due to their extensive tunability and resemblance to the extracellular matrix (ECM), which has a three-dimensional (3D) structure. These features enable various applications that enhance stem cell maintenance and function. However, fast and simple hydrogel fabrication methods are desirable for stem cells for efficient encapsulation and to reduce adverse effects on the cells. In this study, we present a one-pot double-crosslinked hydrogel consisting of polyethylene glycol (PEG) and collagen, which can be prepared without the multi-step sequential synthesis of each network, by using bio-orthogonal chemistry. To enhance the adipogenic differentiation efficiency of adipose-derived stem cells (ADSCs), we added degradable components within the hydrogel to regulate matrix stiffness through cell-mediated degradation. Bio-orthogonal reactions used for hydrogel gelation allow rapid gel formation for efficient cell encapsulation without toxic by-products. Furthermore, the hybrid network of synthetic (PEG) and natural (collagen) components demonstrated adequate mechanical strength and higher cell adhesiveness. Therefore, ADSCs grown within this hybrid hydrogel proliferated and functioned better than those grown in the single-crosslinked hydrogel. The degradable elements further improved adipogenesis in ADSCs with dynamic changes in modulus during culture and enabled the retrieval of differentiated cells for potential future applications.

Trends in nano-platforms for the treatment of viral infectious diseases.

Viral diseases have always been a major health issue, from the currently eradicated poliovirus to the still unresolved human immunodeficiency virus, and have since become a recent global threat brought about by the COVID-19 pandemic. Pathogenic viruses easily spread through various means such as contaminated food and water intake, exchange of bodily fluids, or even inhalation of airborne particles mainly due to their miniscule size. Furthermore, viral coats contain virulent proteins which trigger assimilation into target cells on contact through either direct penetration or induction of endocytosis. In some viruses their outer envelope contains masking ligands that create a means of escape from detection of immune cells. To deal with the nanometer size range and biomolecular-based invasion mechanism, nanoparticles are highly suitable for the treatment. The review highlights the progress in nanoparticle technology, particularly viral therapeutics, including therapeutic strategies and existing clinical applications.

Nanosome-Mediated Delivery Of Hdac Inhibitors and Oxygen Molecules for the Transcriptional Reactivation of Latent Hiv-Infected Cd4+ T Cells.

The treatment of human immunodeficiency virus (HIV) infection is notoriously difficult due to the ability of this virus to remain latent in the host's CD4+ T cells. Histone deacetylases (HDACs) interfere with DNA transcription in HIV-infected hosts, resulting in viral latency. Therefore, HDAC inhibitors can be used to activate viral transcription in latently infected cells, after which the virus can be eliminated through a shock-and-kill strategy. Here, a drug delivery system is developed to effectively deliver HDAC inhibitors to latent HIV-infected cells. Given that the efficacy of HDAC inhibitors is reduced under hypoxic conditions, oxygen-containing nanosomes are used as drug carriers. Oxygen-containing nanosomes can improve the efficiency of chemotherapy by delivering essential oxygen to cells. Additionally, their phospholipid bilayer structure makes them uniquely well-suited for drug delivery. In this study, a novel drug delivery system is developed by taking advantage of the oxygen carriers in these oxygen nanosomes, incorporating a multi-drug strategy consisting of HDAC inhibitors and PKA activators, and introducing CXCR4 binding peptides to specifically target CD4+ T cells. Oxygen nanosomes with enhanced targeting capability through the introduction of the CXCR4 binding peptide mitigate drug toxicity and slow down drug release. The observed changes in the expression of p24, a capsid protein of HIV, indirectly confirm that the proposed drug delivery system can effectively induce transcriptional reactivation of HIV in latent HIV-infected cells.

Brugada Syndrome Unmasked by Cellulitis of the Face.

A 35-year-old male patient with no specific history visited an emergency medical center with a chief complaint of facial swelling accompanied by fever (38.3°C). Contrast-enhanced facial computed tomography confirmed diffuse soft tissue swelling and facial infiltration of inflammation. Additional laboratory findings revealed elevated white blood cell count and C-reactive protein level. The patient also complained of chest pain; therefore, electrocardiography was performed, which confirmed a curved pattern-like ST-segment elevation (≥2 mm) of V2 without elevated cardiac enzyme levels. Based on various test results, the patient was diagnosed with Brugada syndrome. He was administered intravenous empirical antibiotics and intravenous ibuprofen as an antipyretic for the treatment of facial cellulitis and Brugada syndrome. After the resolution of the symptoms, his body temperature normalized. A subsequent electrocardiogram confirmed a normal sinus rhythm pattern. This case report shows that Brugada syndrome, a rare but life-threatening disease, can be unmasked by facial cellulitis. Because antipyretics can immediately reduce the critical rate of sudden cardiac death, Brugada syndrome should be differentially diagnosed, with an evaluation of facial cellulitis, to prevent sudden cardiac death.

Scalp metastasis from an adenocarcinoma of the lung mimicking a cystic mass: case report and literature review.

A 67-year-old man visited our plastic surgery clinic complaining of a palpable protruding mass (2.0 × 2.5 cm) in the right occipital region. To establish an appropriate treatment plan for the cystic mass, brain magnetic resonance imaging was performed. A 2.2 cm nodular lesion with peripheral enhancement in the right occipital region of the scalp was confirmed. In addition, two rim-enhancing nodular lesions up to 9 mm with marked perilesional edema in the right frontal lobe were confirmed. The findings suggested metastasis from cancer. After further evaluations, a mass in the right lower lung field was identified as adenocarcinoma of the lung. Histological examination characterized the excised lesion as a cutaneous metastasis from lung adenocarcinoma. This case report shows that a cystic mass, which commonly occurs in the scalp, may indicate lung cancer. In particular, if a cystic mass of the scalp is identified in a person at high risk for lung cancer, appropriate evaluation and urgent treatment should be performed.

Calcipotriol, a synthetic Vitamin D analog, promotes antitumor immunity via CD4+T-dependent CTL/NK cell activation.

To overcome the hurdles of immunotherapy, we investigated whether calcipotriol, a synthetic vitamin D analog, could overcome the immune evasion of glioblastoma multiforme (GBM) by modulating immune responses and the immunosuppressive tumor microenvironment. Administration of calcipotriol considerably reduced tumor growth. Both in vivo and in vitro studies revealed that CD8+T and natural killer (NK) cell gene signatures were enriched and activated, producing high levels of IFN-γ and granzyme B. In contrast, regulatory T cells (Treg) were significantly reduced in the calcipotriol-treated group. The expression of CD127, the receptor for thymic stromal lymphopoietin (TSLP), is elevated in CD4+T cells and potentially supports T-cell priming. Depleting CD4+T cells, but not NK or CD8+T cells, completely abrogated the antitumor efficacy of calcipotriol. These data highlight that the calcipotriol/TSLP/CD4+T axis can activate CD8+T and NK cells with a concomitant reduction in the number of Tregs in GBM. Therefore, calcipotriol can be a novel therapeutic modality to overcome the immune resistance of GBM by converting immunologically "cold" tumors into "hot" tumors. DATA AVAILABILITY: Data are available upon reasonable request. The RNA-seq dataset comparing the transcriptomes of control and calcipotriol-treated GL261 tumors is available from the corresponding author upon request.

Primary Mucormycosis Infection in the Submandibular Area After Esthetic Lipolytic Injection in An Immunocompetent Patient: A Case Report.

As the popularity of injection lipolysis increases, several side effects of injection lipolysis have been reported. In this case, A 53-year-old woman visited our outpatient clinic with a new round-shaped protruding mass (size: 5.0 cm × 3.0 cm) in the submental area. The patient had received the injection lipolysis treatment before the visit. She had received injections in the submental area at 1-week intervals (i.e., 4, 5, and 6 weeks). We performed contrast-enhanced computed tomography of the neck for differential diagnosis and found a 5.0 cm × 3.7 cm × 2.1 cm rim-enhanced fluid-density lesion in the submental. Hence, surgical removal of the lesion was planned based on the diagnosis of unspecified complicated fluid collection. The removed mass was a 3.0 cm × 2.0 cm × 2.0 cm whitish fibrous tissue. Histological examination revealed mucormycosis infection. Although several side effects of lipolysis have been reported to date, mucormycosis infection in the submental area has not been reported before.

XAF1 directs glioma response to temozolomide through apoptotic transition of autophagy by activation of ATM-AMPK signaling.

Background: X-linked inhibitor of apoptosis-associated factor 1 (XAF1) is a tumor suppressor that is commonly inactivated in multiple human cancers. However, its role in the pathogenesis and therapeutic response of glioma is poorly characterized. Methods: XAF1 activation by temozolomide (TMZ) and its effect on TMZ cytotoxicity were defined using luciferase reporter, flow cytometry, and immunofluorescence assays. Signaling mechanism was analyzed using genetic and pharmacologic experiments. In vivo studies were performed in mice to validate the role of XAF1 in TMZ therapy. Results: Epigenetic alteration of XAF1 is frequent in cell lines and primary tumors and contributes to cancer cell growth. XAF1 transcription is activated by TMZ via JNK-IRF-1 signaling to promote apoptosis while it is impaired by promoter hypermethylation. In tumor cells expressing high O 6-methylguanine-DNA methyltransferase (MGMT), XAF1 response to TMZ is debilitated. XAF1 facilitates TMZ-mediated autophagic flux to direct an apoptotic transition of protective autophagy. Mechanistically, XAF1 is translocated into the mitochondria to stimulate reactive oxygen species (ROS) production and ataxia telangiectasia mutated (ATM)-AMP-activated protein kinase (AMPK) signaling. A mutant XAF1 lacking the zinc finger 6 domain fails to localize in the mitochondria and activate ROS-ATM-AMPK signaling and autophagy-mediated apoptosis. XAF1-restored xenograft tumors display a reduced growth rate and enhanced therapeutic response to TMZ, which is accompanied with activation of ATM-AMPK signaling. XAF1 expression is associated with overall survival of TMZ treatment patients, particularly with low MGMT cancer. Conclusions: This study uncovers an important role for the XAF1-ATM-AMPK axis as a linchpin to govern glioma response to TMZ therapy.

Assessment of human adipose-derived stem cell on surface-modified silicone implant to reduce capsular contracture formation.

Medical devices made from poly(dimethylsiloxane) (PDMS)-based silicone implants have been broadly used owing to their inert properties, biocompatibility, and low toxicity. However, long-term implantation is usually associated with complications, such as capsular contracture due to excessive local inflammatory response, subsequently requiring implant removal. Therefore, modification of the silicone surface to reduce a risk of capsular contracture has attracted increasing attention. Human adipose-derived stem cells (hASCs) are known to provide potentially therapeutic applications for tissue engineering, regenerative medicine, and reconstructive surgery. Herein, hASCs coating on a PDMS (hASC-PDMS) or itaconic acid (IA)-conjugated PDMS (hASC-IA-PDMS) surface is examined to determine its biocompatibility for reducing capsular contracture on the PDMS surface. In vitro cell cytotoxicity evaluation showed that hASCs on IA-PDMS exhibit higher cell viability than hASCs on PDMS. A lower release of proinflammatory cytokines is observed in hASC-PDMS and hASC-IA-PDMS compared to the cells on plate. Multiple factors, including in vivo mRNA expression levels of cytokines related to fibrosis; number of inflammatory cells; number of macrophages and myofibroblasts; capsule thickness; and collagen density following implantation in rats for 60 days, indicate that incorporated coating hASCs on PDMSs most effectively reduces capsular contracture. This study demonstrates the potential of hASCs coating for the modification of PDMS surfaces in enhancing surface biocompatibility for reducing capsular contracture of PDMS-based medical devices.