Biomarkers from subcutaneous engineered tissues predict acute rejection of organ allografts.

Invasive graft biopsies assess the efficacy of immunosuppression through lagging indicators of transplant rejection. We report on a microporous scaffold implant as a minimally invasive immunological niche to assay rejection before graft injury. Adoptive transfer of T cells into Rag2-/- mice with mismatched allografts induced acute cellular allograft rejection (ACAR), with subsequent validation in wild-type animals. Following murine heart or skin transplantation, scaffold implants accumulate predominantly innate immune cells. The scaffold enables frequent biopsy, and gene expression analyses identified biomarkers of ACAR before clinical signs of graft injury. This gene signature distinguishes ACAR and immunodeficient respiratory infection before injury onset, indicating the specificity of the biomarkers to differentiate ACAR from other inflammatory insult. Overall, this implantable scaffold enables remote evaluation of the early risk of rejection, which could potentially be used to reduce the frequency of routine graft biopsy, reduce toxicities by personalizing immunosuppression, and prolong transplant life.

Sensitivity of Each Index of Doppler, Cross, Uncollapsible, Parallel, and Superficial Fascia in Lymphatic Ultrasound.

Background: Recently, the usefulness of lymphatic ultrasound has been reported. It is beneficial not only to identify lymphatic vessels but also to evaluate lymphatic degeneration and diagnose lymphedema. We previously proposed D-CUPS (Doppler, Cross, Uncollapsible, Parallel, and Superficial fascia) to identify the lymphatic vessels on ultrasound. The purpose of this study was to clarify the sensitivity of each index of D-CUPS. Methods: We performed a retrospective study of 27 patients (44 limbs, 98 sites) with lower extremity lymphedema, who underwent lymphaticovenous anastomosis (LVA). We performed a lymphatic ultrasound the day before surgery. We used a linear probe commonly used for venous ultrasound (Noblus EUP-L65; Hitachi Medical Corp., Tokyo, Japan). We applied the D-CUPS index to identify the lymphatic vessels on ultrasound. We checked whether lymphatic vessels consistent with preoperative lymphatic ultrasound findings were observed during the LVA. We also calculated the sensitivity of each D-CUPS index. Results: All the 27 patients were women, with a mean age of 59.7 years. Totally, 98 incisions were made (59 incisions on the thigh and 39 incisions on the lower leg). During LVA, lymphatic vessels consistent with the preoperative lymphatic ultrasound findings were observed at all the sites. The sensitivities of each indicator of D-CUPS were 100.0%, 100.0%, 68.4%, 19.4%, and 100.0%, respectively. Conclusion: The sensitivity was 100.0% in D, C, and S. Although each index separately was not perfect, by combining them appropriately, we were able to identify lymphatic vessels with certainty.

5-year Follow-up of Reimplanted Parathyroid Glands in Forearm Subcutaneous Tissue During Thyroidectomy. A Confirmation of Graft Vitality in a Large Series of Patients.

INTRODUCTION: The aim of this study is to assess the outcomes of parathyroid gland reimplantation with PR-FaST technique in patients undergoing thyroid surgery, focusing on graft functionality over a 5-year follow-up period. MATERIALS AND METHODS: We analyzed data from 131 patients who underwent parathyroid reimplantation using the PR-FaST technique during thyroid surgery due to inadvertent parathyroid removal or evident vascular damage. Postoperative evaluations included serum calcium (Ca), magnesium (Mg), and phosphorus (P) analyses on the 1st and 2nd postoperative days, at 10 days, and at 1, 3, 6 months, 1 year, and 5 years of follow-up. Additionally, the mean values of serum intact parathyroid hormone (iPTH) concentration were measured from blood samples collected from both the reimplanted arm (iPTH RA) and non-reimplanted arm (iPTH NRA) within the same period. RESULTS: Among 131 patients, at 10 days post-surgery, only 46 patients (35.1%) out of 131 exhibited graft viability (iPTH ratio >1.5). This percentage increased to 72.8% (94 patients) after 1 month and further to 87.8% (108 patients) after 3 months post-surgery. At 1 year, 84.7% of patients showed good graft functionality. After 5 years, the percentage remained stable, with graft viability observed in 81.3% of patients. Only 91 of the initial 131 patients completed follow-up up to 5 years, with a dropout rate of 30.5 %. CONCLUSIONS: Parathyroid reimplantation using the PR-FaST technique is a viable option for patients undergoing thyroidectomy and has been shown to be a reproducible and effective technique in most patients, with sustained graft functionality and parathyroid hormone production over a 5-year follow-up period.

Cutaneous, Subcutaneous, and Bilateral Adrenal Gland Metastases in Progressive Prostate Carcinoma: Theranostic Potential of 68 Ga-PSMA-11 PET/CT Imaging and 177 Lu-PSMA-617 Therapy.

ABSTRACT: Prostate carcinoma (PC) is the second most common malignant tumor in males globally. The metastatic spread of PC usually involves the pelvic and abdominal lymph nodes and the skeletal system. Cutaneous metastases are exceedingly uncommon and typically manifest themselves late in the disease course, considered as ominous sign with limited treatment options and a poor prognosis. We describe a patient wherein 68 Ga-PSMA-11 PET/CT detected multiple uncommon metastatic sites in the cutaneous region of the scrotum, penis, and thigh, as well as in the subcutaneous region of anterior abdominal wall, and in bilateral adrenal glands. These findings served as a theranostic tool for selecting 177 Lu-PSMA-617 treatment for these extremely rare metastatic sites.

Histological analysis of the dermal and hypodermal layers of the face and correlation with high-frequency 24 MHz ultrasonography and elastosonography.

Knowledge of the structure of the face is of fundamental importance. In fact, the face is treated in many areas of medicine, from dermatology, to maxillofacial surgery, to otorhinolaryngology, to ophthalmology, etc. and anti-aging aesthetic treatments, and those for the resolution of blemishes are on the increase. For ethical reasons it is not possible to take biopsy samples for facial analysis in the aesthetic field. The main aim of this study was to demonstrate that a high-resolution bimodal ultrasound examination, combined with elastosonography, could be a valid tool for pre-treatment morphological evaluation. To achieve this goal, skin samples were taken from the forehead, zygomatic area, nasolabial fold, upper and lower lip from cadavers to histologically characterize their structure. Subsequently, these same areas were evaluated in vivo using conventional B-mode ultrasound with a 24 MHz high-frequency probe, and elastosonography. The data obtained with the different techniques were compared, in order to state that modern ultrasound techniques can provide similar histological information. The analysis showed that the superficial hypodermis presented a different shape and structure in the different areas, with the exception of the areas of the upper and lower lip, which appeared similar. With aging, the forehead and zygomatic area showed a volumetric increase in the superficial hypodermic layer, while the lip showed non-structural changes. The morphology of the nasolabial fold remained unchanged. When it is not possible to perform histological investigations on the face, to understand its characteristics and dynamics, ultrasound with a 24 MHz probe would seem to be the most suitable method, while elastosonography could be a valid method for evaluating the stiffness of the structural components.

Clinical Investigation of Large Volume Subcutaneous Delivery up to 25 mL for Lean and Non-Lean Subjects.

PURPOSE: To evaluate the clinical feasibility and tolerability of large volume subcutaneous delivery at different injection depths for lean and non-lean subjects. METHODS: A single-center, randomized, subject-blinded, crossover study in 62 healthy subjects was conducted to evaluate delivery of a 10-cP solution containing hyaluronic acid. Subjects were separated into lean and non-lean cohort by SC thickness. A syringe pump was used to study the effect of different volumes (5, 12, 25 mL) of a viscous placebo solution and needle lengths (6, 9 and 12 mm) delivered at 0.5 mL/min. RESULTS: Across all treatments, injection sites were observed to have negligible leakage, ~34 kPa of back pressure, and VAS of mild pain with higher pain from needle insertion than during injection. While mild to moderate erythema was the most frequently reported ISR and edema was most prominent for 25 mL injections, all ISRs were resolved within 4 hours post injection. Subjects were unbothered by ISRs across all treatments and rated them as low distress scores (average 1.0-1.5 out of 6). CONCLUSION: SC injection of 25 mL is feasible and tolerable using a low-pain formulation for abdomen injection irrespective of subcutaneous thickness and injection depths at a delivery rate of 0.5 mL/min.

Poroelastic Characterization and Modeling of Subcutaneous Tissue Under Confined Compression.

Subcutaneous tissue mechanics are important for drug delivery. Yet, even though this material is poroelastic, its mechanical characterization has focused on its hyperelastic response. Moreover, advancement in subcutaneous drug delivery requires effective tissue mimics such as hydrogels for which similar gaps of poroelastic data exist. Porcine subcutaneous samples and gelatin hydrogels were tested under confined compression at physiological conditions and strain rates of 0.01%/s in 5% strain steps with 2600 s of stress relaxation between loading steps. Force-time data were used in an inverse finite element approach to obtain material parameters. Tissues and gels were modeled as porous neo-Hookean materials with properties specified via shear modulus, effective solid volume fraction, initial hydraulic permeability, permeability exponent, and normalized viscous relaxation moduli. The constitutive model was implemented into an isogeometric analysis (IGA) framework to study subcutaneous injection. Subcutaneous tissue exhibited an initial spike in stress due to compression of the solid and fluid pressure buildup, with rapid relaxation explained by fluid drainage, and longer time-scale relaxation explained by viscous dissipation. The inferred parameters aligned with the ranges reported in the literature. Hydraulic permeability, the most important parameter for drug delivery, was in the range k 0 ∈ [ 0.142 , 0.203 ] mm 4 /(N s). With these parameters, IGA simulations showed peak stresses due to a 1-mL injection to reach 48.8 kPa at the site of injection, decaying after drug volume disperses into the tissue. The poro-hyper-viscoelastic neo-Hookean model captures the confined compression response of subcutaneous tissue and gelatin hydrogels. IGA implementation enables predictive simulations of drug delivery.

Whole-exome sequencing is feasible on a fresh-frozen skin sample of intravascular large B cell lymphoma.

Intravascular large B-cell lymphoma (IVLBCL) is a rare aggressive extranodal non-Hodgkin lymphoma. The predominant, if not exclusive, growth of neoplastic cells within the lumina of small-sized vessels represents the hallmark of the disease. Diagnosis is challenging due to the absence of marked lymphadenopathy, the highly heterogeneous clinical presentation, and the rarity of the condition. Clinical presentation is characterized by variable combinations of nonspecific signs and symptoms (such as fever and weight loss), organ-specific focal manifestations due to altered perfusion, and hemophagocytic syndrome. The rarity of this entity and the paucity of neoplastic cells in biopsy samples hamper the study of recurrent molecular abnormalities. The purpose of this study was to explore the feasibility of a different approach to recover a sufficient amount of DNA of acceptable quality to perform next-generation sequencing studies. Here, we report the findings of whole-exome next-generation sequencing performed on a fresh-frozen cutaneous sample of IVLBCL, paired with the patient saliva used as germline DNA. To increase the cancer cell fraction, only the subcutaneous tissue was selected. With this approach, we obtained high-quality DNA and were able to identify oncogenic mutations specific for this entity and recapitulating its post-germinal center origin, even if the tumor fraction was low. Molecular studies performed on fresh-frozen cutaneous sample are feasible in IVLBCL, especially when analysis is restricted to the subcutaneous tissue. Wide adoption of this reproducible and cost-effective approach may foster further studies, which may be of help in supporting diagnosis, providing pathogenetic insights, and guiding treatment decisions.

Reconstructed Human Skin with Hypodermis Shows Essential Role of Adipose Tissue in Skin Metabolism.

BACKGROUND: Dysregulation of skin metabolism is associated with a plethora of diseases such as psoriasis and dermatitis. Until now, reconstructed human skin (RhS) models lack the metabolic potential of native human skin, thereby limiting their relevance to study human healthy and diseased skin. We aimed to determine whether incorporation of an adipocyte-containing hypodermis into RhS improves its metabolic potential and to identify major metabolic pathways up-regulated in adipose-RhS. METHODS: Primary human keratinocytes, fibroblasts and differentiated adipose-derived stromal cells were co-cultured in a collagen/fibrin scaffold to create an adipose-RhS. The model was extensively characterized structurally in two- and three-dimensions, by cytokine secretion and RNA-sequencing for metabolic enzyme expression. RESULTS: Adipose-RhS showed increased secretion of adipokines. Both RhS and adipose-RhS expressed 29 of 35 metabolic genes expressed in ex vivo native human skin. Addition of the adipose layer resulted in up-regulation of 286 genes in the dermal-adipose fraction of which 7 were involved in phase I (CYP19A1, CYP4F22, CYP3A5, ALDH3B2, EPHX3) and phase II (SULT2B1, GPX3) metabolism. Vitamin A, D and carotenoid metabolic pathways were enriched. Additionally, pro-inflammatory (IL-1ß, IL-18, IL-23, IL-33, IFN-α2, TNF-α) and anti-inflammatory cytokine (IL-10, IL-12p70) secretion was reduced in adipose-RhS. CONCLUSIONS: Adipose-RhS mimics healthy native human skin more closely than traditional RhS since it has a less inflamed phenotype and a higher metabolic activity, indicating the contribution of adipocytes to tissue homeostasis. Therefore it is better suited to study onset of skin diseases and the effect of xenobiotics.

Bone and Skin/Subcutaneous Tissue Concentrations of Cefiderocol During Treatment of Extensively Drug-Resistant Pseudomonas aeruginosa.

Pyoderma gangrenosum is a rare dermatologic disorder that disrupts the skin barrier, requiring immunosuppressive therapy. We successfully used cefiderocol for the treatment of an extensively drug-resistant Pseudomonas aeruginosa bacteremia, and presumed osteomyelitis in a patient with severe pyoderma gangrenosum and associated immunosuppressive therapy while being medically optimized for skin grafting. We obtained bone and skin/subcutaneous tissue while the patient was on cefiderocol under an institutional review board-approved biologic waste recovery protocol. Cefiderocol concentrations in bone and skin/subcutaneous tissue were 13.9 and 35.9 mcg/g, respectively. The patient recovered from bacteremia and underwent autografting without further complications. Cefiderocol at approved dosing of 2 g IV (3-hour infusion) every 8 hours resulted in bone and skin/subcutaneous tissue concentrations adequate to treat extensively drug-resistant Gram-negative bacteria that remain susceptible to cefiderocol.

Bioactive potential of Bio-C Temp demonstrated by systemic mineralization markers and immunoexpression of bone proteins in the rat connective tissue.

Intracanal medications are used in endodontic treatment due to their antibacterial activity and ability to induce the periapical repair. Among the intracanal medications, the Calen (CAL; SS. White, Brazil) is a calcium hydroxide-based medication that provides an alkaline pH and releases calcium, exerting an antimicrobial activity. Bio-C Temp (BIO; Angelus, Brazil), a ready-to-use bioceramic intracanal medication, was designed to stimulate the mineralized tissues formation. Here, we investigated the bioactive potential of BIO in comparison to the CAL in the rat subcutaneous. Polyethylene tubes filled with medications, and empty tubes (control group, CG) were implanted in the subcutaneous tissue of rats. After 7, 15, 30 and 60 days, the blood was collected for calcium (Ca+2) and alkaline phosphatase (ALP) measurement, and the capsules around the implants were processed for morphological analyses. The data were submitted to two-way ANOVA and Tukey test (p < 0.05). At 7, 15 and 30 days, the ALP level was grater in BIO and CAL than in CG (p < 0.0001). At 7 and 15 days, greater Ca+2 level was seen in the serum of CAL samples. From 7 to 60 days, an increase in the number of fibroblasts, osteocalcin- and osteopontin-immunolabelled cells was observed in BIO and CAL groups (p < 0.0001). In all periods, BIO and CAL specimens showed von Kossa-positive structures. Moreover, ultrastructural analysis revealed globules of mineralization in the capsules around the BIO and CAL specimens. Thus Bio-C Temp caused an increase in the ALP, osteocalcin and osteopontin, which may have allowed the formation of calcite, suggesting bioactive potential.

Molecular Retention Limitations for Prevascularized Subcutaneous Sites for Islet Transplantation.

Beta cell replacement therapies utilizing the subcutaneous space have inherent advantages to other sites: the potential for increased accessibility, noninvasive monitoring, and graft extraction. Site prevascularization has been developed to enhance islet survivability in the subcutaneous zone while minimizing potential foreign body immune responses. Molecular communication between the host and prevascularized implant site remains ill-defined. Poly(ethylene oxide)s (PEOs) of various hydrated radii (i.e., ∼11-62 Å) were injected into prevascularized subcutaneous sites in C57BL/6 mice, and the clearance and organ biodistribution were characterized. Prevascularization formed a barrier that confined the molecules compared with the unmodified site. Molecular clearance from the prevascularized site was inversely proportional to the molecular weight. The upper limit in molecular size for entering the vasculature to be cleared was determined to be 35 kDa MW PEO. These findings provide insight into the impact of vascularization on molecular retention at the injection site and the effect of molecular size on the mobility of hydrophilic molecules from the prevascularized site to the host. This information is necessary for optimizing the transplantation site for increasing the beta cell graft survival.

Morphofunctional and histological patterns of blood vessels in the superficial cervicofacial musculoaponeurotic system in midlateral face regions.

OBJECTIVE: The superficial cervicofacial musculoaponeurotic system (SMAS) is a complex network formed by mimic muscles and conjunctive tissue of the superficial fascia of the face.This study aimed to introduce new anatomofunctional data on the importance of the trans-SMAS distribution pattern of the skin microperfusion of the face and to underline the role of SMAS in maintaining the homeostasis of the vascular network that crosses it. Considering the fibrous and muscular matrix of the SMAS, using COLIII and MyoH2 antibodies, together with endothelial immunohistochemistry(IHC)intercellular adhesion molecule 2 marker, we determined the correlation of these structures and their interaction. METHODS: This study included 33donors of SMAS tissues, which have been stained withregular hematoxylin and eosin (HE), and three different IHC markers have been used (collagen III, muscular tissue, and blood vessels). The samples were collected from parotid, masseteric, jugal, and zygomatic regions. Magnetic resonance angiography was used to identify the main vascular sources of the midlateral regions of the face of another 47 patients. RESULTS: Significant differences in topographic arrangement, density, and relations of the microsopic vasculature were observed between each of the four regions. Major differences were identified between the role of SMAS in each of these regions, from the parotid capsule to masseteric fascia, transition mobile part, and attaching manners in the zygomatic subunit. CONCLUSIONS: Blood vessel topography must be related with the surrounding conjunctive and muscular tissue, especially regarding facial SMAS. Intrinsic relations between these three components of the SMAS and nervous fibers can provide us important hints on the functionality of the whole system.

Could subcutaneous rifampicin administration be an effective approach for reducing episiotomy infections?

OBJECTIVE: The aim of this prospective cross-sectional study was to investigate whether cleaning the episiotomy line with rifampicin solution before suturing will reduce infection and wound dehiscence in women who had vaginal delivery with episiotomy. PATIENTS AND METHODS: A prospective cross-sectional study was conducted with a total of 400 primigravida patients. In the study group, irrigation with rifampicin of the subcutaneous tissue of the episiotomy incision was applied, and in the control group, there was no irrigation. Patients were evaluated for infection at the 1st, 3rd week, and 1-month controls. The groups were compared according to episiotomy infection and wound dehiscence rates. RESULTS: The episiotomy infection rate of the whole group was 8.5%, the wound dehiscence rate was 3.75%, and the average time of occurrence of the infection was 5.35±2.21 days. The most common infection findings were local pain and purulent discharge at 4.75%. In the control group, where the infection occurred earlier, the infection and wound dehiscence rates were significantly higher [11.5% vs. 5.5%; 6.0% vs. 1.5% (p<0.05)]. Purulent discharge was the most common finding in the control group, and local pain in the study group, but no significant difference was found between the two groups in terms of findings (p<0.05). When only the patients who developed episiotomy infection were evaluated among themselves, the only significant difference was found in wound dehiscence, which was higher in the control group (p<0.05). CONCLUSIONS: Considering the high rates of episiotomy in our country, subcutaneous irrigation with rifampicin is a good option that can be kept in the foreground due to its low cost and ease of application.

Noninvasive identification of directionally-dependent elastic properties of soft tissues using full-field optical data.

This paper introduces an innovative approach for elastic property characterization of soft tissues, having directional-dependent material behavior, via their vibration response measurement and interpretation. The full-field time-dependent surface displacements as a result of externally excited soft tissues are collected through digital image correlation (DIC). A developed analytical model, capturing the low-amplitude vibration behavior of anisotropic layered human skin with the incorporation of the influence of subcutaneous elasticity and inertia, is employed to accurately predict its resonant frequencies and pertaining displacement field images. An efficient solution approach for the model is implemented into an inverse algorithm to rapidly characterize the anisotropic elastic properties based on importing the vibration characteristics. To show the merit of the approach, a 3-D finite element (FE) simulation model was used to generate full-field data, detected and matched with a set of specific vibration modes via modal assurance criterion (MAC). The validity of the model implemented into the inverse characterization algorithm is demonstrated through a comparison of predicted vibration frequencies and mode-shapes simulated via the 3-D FE model for different cases with anisotropic elastic properties in different layers of the skin. It is shown that modes are influenced differently when anisotropic properties are introduced to the model. Thus, the established inverse characterization algorithm is capable of rapidly predicting the elastic material properties of anisotropic soft sheets with adequate accuracy.

Impact of Prevascularization on Immunological Environment and Early Engraftment in Subcutaneous Islet Transplantation.

BACKGROUND: The utilization of islet-like cells derived from pluripotent stem cells may resolve the scarcity of islet transplantation donors. The subcutaneous space is a promising transplantation site because of its capacity for graft observation and removal, thereby ensuring safety. To guarantee subcutaneous islet transplantation, physicians should ensure ample blood supply. Numerous methodologies, including prevascularization, have been investigated to augment blood flow, but the optimal approach remains undetermined. METHODS: From C57BL/6 mice, 500 syngeneic islets were transplanted into the prevascularized subcutaneous site of recipient mice by implanting agarose rods with basic fibroblast growth factor at 1 and 2 wk. Before transplantation, the blood glucose levels, cell infiltration, and cytokine levels at the transplant site were evaluated. Furthermore, we examined the impact of the extracellular matrix capsule on graft function and the inflammatory response. RESULTS: Compared with the 1-wk group, the 2-wk group exhibited improved glycemic control, indicating that longer prevascularization enhanced transplant success. Flow cytometry analysis detected immune cells, such as neutrophils and macrophages, in the extracellular matrix capsules, whereas cytometric bead array analysis indicated the release of inflammatory and proinflammatory cytokines. Treatment with antitumor necrosis factor and anti-interleukin-6R antibodies in the 1-wk group improved graft survival, similar to the 2-wk group. CONCLUSIONS: In early prevascularization before subcutaneous transplantation, neutrophil and macrophage accumulation prevented early engraftment owing to inflammatory cytokine production.

Anatomical Relationship between the Inferior Temporal Septum and the Temporal Branch of the Facial Nerve for Clinical Applications.

BACKGROUND: The inferior temporal septum (ITS) is a fibrous adhesion between the superficial temporal fascia and the superficial layer of the deep temporal fascia. This study identified detailed the anatomical relationship between the ITS and the temporal branch of the facial nerve (TBFN) for facial nerve preservation during temple interventions. METHODS: Among 33 Korean cadavers, 43 sides of TBFNs in temporal regions were dissected after identifying the ITS between the superficial temporal fascia and superficial layer of the deep temporal fascia through blunt dissection. The topography of the ITS and TBFN were investigated with reference to several facial landmarks. Regional relationships with the ITS and TBFN within the temporal fascial layers were histologically defined from five specimens. RESULTS: At the level of the inferior orbital margin by the tragion, the mean distances from the lateral canthus to the anterior and posterior branches of the TBFN were 5 and 6.2 cm, respectively. At the lateral canthus level, the mean distance from the lateral canthus to the posterior branch of the TBFN was similar to that to the ITS, at 5.5 cm. At the superior orbital margin level, the posterior branch of the TBFN ran cranial to the ITS adjacent to the frontotemporal region. The TBFN ran through the subsuperficial temporal fascia layer and the nerve fibers located cranially, and within the ITS meshwork in the upper temporal compartment. CONCLUSION: The area of caution during superficial temporal fascia interventions related to the TBFN was clearly identified in the upper temporal compartment, which is known to lack important structures.

Subcutaneous tissue reaction to a novel nano zinc oxide eugenol dental cement.

BACKGROUND: Zinc oxide eugenol (ZOE) cement is a popular dental material due mainly to its analgesic, antibacterial and anti-inflammatory effects. The formulation of ZOE cement from nano particle-sized zinc oxide (ZnO) has the potential to increase these properties as well as reduce its adverse effects to the surrounding tissues. OBJECTIVE: This study evaluated the subcutaneous tissue response towards nano ZOE cements (ZOE-A and ZOE-B) in comparison to conventional ZOE (ZOE-K). METHODS: Test materials were implanted into 15 New Zealand white rabbits. Tissue samples were obtained after 7, 14, and 30 days (n = 5 per period) for histopathological evaluation of inflammatory cell infiltrate, fibrous tissue condensation, and abscess formation. RESULTS: ZOE-A showed the lowest score for the variable macrophage and lymphocyte at day 7. Both ZOE-A and ZOE-B presented lower fibrous tissue condensation and abscess formation compared to conventional ZOE-K. By day 30, ZOE-A exhibited less lymphocytic and neutrophilic infiltrate compared to the other materials, while ZOE-B had the lowest score for macrophages. ZOE-K exerted higher inflammatory cell response at almost all of the experimental periods. All of the materials resulted in thin fiber condensation after 30 days. CONCLUSIONS: Rabbit tissue implanted with ZOE-A and ZOE-B showed better response compared to ZOE-K.

Calcinosis universalis accompanied by symptomatic systemic sclerosis.

Calcinosis cutis is represented by the deposition of insoluble calcium salts in the skin and subcutaneous tissue. Calcinosis can lead to repeated episodes of local inflammation and repeated infections, resulting in pain and functional disability, and even death. Here, we present a case of a patient with SSc who experienced calcinosis universalis and eventually died from recurrent infections at the sacrococcygeal calcification.