Plasma-Based Scaffold Containing Bone-Marrow Mononuclear Cells Promotes Wound Healing in a Mouse Model of Pressure Injury.

Pressure injuries, or pressure ulcers, are a common problem that may lead to infections and major complications, besides being a social and economic burden due to the costs of treatment and hospitalization. While surgery is sometimes necessary, this also has complications such as recurrence or wound dehiscence. Among the newer methods of pressure injury treatment, advanced therapies are an interesting option. This study examines the healing properties of bone marrow mononuclear cells (BM-MNCs) embedded in a plasma-based scaffold in a mouse model. Pressure ulcers were created on the backs of mice (2 per mouse) using magnets and assigned to a group of ulcers that were left untreated (Control, n = 15), treated with plasma scaffold (Plasma, n = 15), or treated with plasma scaffold containing BM-MNC (Plasma + BM-MNC, n = 15). Each group was examined at three time points (3, 7, and 14 days) after the onset of treatment. At each time point, animals were subjected to biometric assessment, bioluminescence imaging, and tomography. Once treatment had finished, skin biopsies were processed for histological and wound healing reverse transcription polymerase chain reaction (RT-PCR) array studies. While wound closure percentages were higher in the Plasma and Plasma + BM-MNC groups, differences were not significant, and thus descriptive data are provided. In all individuals, the presence of donor cells was revealed by immunohistochemistry on posttreatment onset Days 3, 7, and 14. In the Plasma + BM-MNC group, less inflammation was observed by positron emission tomography-computed tomography (PET/CT) imaging of the mice at 7 days, and a complete morphometabolic response was produced at 14 days, in accordance with histological results. A much more pronounced inflammatory process was observed in controls than in the other two groups, and this persisted until Day 14 after treatment onset. RT-PCR array gene expression patterns were also found to vary significantly, with the greatest difference noted between both treatments at 14 days when 11 genes were differentially expressed.

Tubulointerstitial nephritis and uveitis syndrome and SARS-CoV-2 infection in an adolescent: just a coincidence in time?

BACKGROUND: Despite recent well-established kidney tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), usually presenting as acute kidney injury (AKI), there are few published cases with SARS-CoV-2-related tubulointerstitial nephritis (TIN). We report an adolescent with TIN and delayed association with uveitis (TINU syndrome), where SARS-CoV-2 spike protein was identified in kidney biopsy. CASE-DIAGNOSIS/TREATMENT: A 12-year-old girl was assessed for a mild elevation of serum creatinine detected during the evaluation of systemic manifestations including asthenia, anorexia, abdominal pain, vomiting, and weight loss. Data of incomplete proximal tubular dysfunction (hypophosphatemia and hypouricemia with inappropriate urinary losses, low molecular weight proteinuria, and glucosuria) were also associated. Symptoms had initiated after a febrile respiratory infection with no known infectious cause. After 8 weeks, the patient tested positive in PCR for SARS-CoV-2 (Omicron variant). A subsequent percutaneous kidney biopsy revealed TIN and immunofluorescence staining with confocal microscopy detected the presence of SARS-CoV-2 protein S within the kidney interstitium. Steroid therapy was started with gradual tapering. Ten months after onset of clinical manifestations, as serum creatinine remained slightly elevated and kidney ultrasound showed mild bilateral parenchymal cortical thinning, a second percutaneous kidney biopsy was performed, without demonstrating acute inflammation or chronic changes, but SARS-CoV-2 protein S within the kidney tissue was again detected. At that moment, simultaneous routine ophthalmological examination revealed an asymptomatic bilateral anterior uveitis. CONCLUSIONS: We present a patient who was found to have SARS-CoV-2 in kidney tissue several weeks following onset of TINU syndrome. Although simultaneous infection by SARS-CoV-2 could not be demonstrated at onset of symptoms, since no other etiological cause was identified, we hypothesize that SARS-CoV-2 might have been involved in triggering the patient's illness.

Spectrum of comorbid autoimmune diseases in patients with chondrodermatitis nodularis helicis: a 17-year retrospective study of 215 patients in Asturias, northern Spain

Background: The cause of chondrodermatitis nodularis helicis (CN) (Winkler's disease) is unknown, but potential associations with autoimmune diseases have been suggested in case reports, however, studies with large case series are lacking. Objectives: To clarify the frequency of chronic inflammatory and autoimmune diseases (CADs), and associated gender and age distribution, in a large cohort of patients with CN. Materials & Methods: The frequency of CADs (systemic and cutaneous) was assessed in 215 patients (65.1% males and 34.9% females; median age: 69.6 years) with a histopathological diagnosis of CN (2000-2017). Endocrine diseases were not included. Statistical analysis included Fisher's exact test and multivariate logistic regression analysis. Results: Twenty different CADs were diagnosed in 15.34% patients with CN. The most frequent were polymyalgia rheumatica (six patients), psoriasis (four patients, one with psoriatic arthritis), rheumatoid arthritis (three patients), CREST syndrome (two patients), vitiligo (two patients), and chronic dermatitis (two patients). Several CADs were strongly associated with tobacco smoking. Systemic CADs were more frequent in females (OR: 3.814; CI 1.513-9.613; p = 0.005; multivariate logistic regression analysis). Differences according to age at onset were not significant. Conclusion: We characterize, for the first time, the spectrum of CADs as well as age and gender distribution in patients with CN based on the largest cohort of patients to date. The possible accumulation of different disorders that are strongly associated with tobacco smoking (Buerger's disease, pulmonary Langerhans cell histiocytosis, rheumatoid arthritis, Lupus erythematosus, and others) merits further investigation, but the rarity of some of them makes this challenging.

Epithelioid angiosarcoma of the skin. A malignant tumor mimicking many different neoplasms.

Epithelioid angiosarcomas are rare malignant mesenchymal tumors. The main problem of these tumors is the complicate clinical and histological diagnosis. We report a case with an immunohistochemical panel. We propose the use of CD31 in the immunohistochemical panel of an undifferenciated tumor with epithelioid features, because it appears to be the only endothelial marker these tumors constantly express.

Primary inverted papilloma of the middle ear with intracranial invasion.

BACKGROUND: Primary inverted papillomas of the middle ear are extremely rare tumors, with only few cases published in the literature. They have a characteristic epithelium surface inversion to the inside of the stroma. Inverted papillomas are benign lesions but have a high propensity of recurrence, local aggressiveness, and association with malignancy. METHODS: We present a patient with an inverted papilloma originating in the middle ear producing chronic otorrhea and facial nerve palsy treated with a subtotal petrosectomy. RESULTS: During the follow-up, the patient developed an intracranial invasion of the tumor causing his death. CONCLUSION: Primary inverted papillomas of the middle ear can have an extremely aggressive behavior despite their benign characteristics; therefore, an aggressive treatment must be performed in order to minimize the possibility of recurrence.

The prognostic role of claudins -1 and -4 in oral squamous cell carcinoma.

Claudin dysregulation has been described in various tumor types; however, its clinical relevance is poorly understood. We present a study in which we assessed the expression of claudin 1 (CLDN1) and CLDN4 in oral squamous cell carcinoma (OSCC), as well as their prognostic relevance. Immunohistochemical analysis of CLDN1 and CLDN4 expression was carried out on tissue sections from 65 OSCCs. The presence of CLDN1 in the invasive front of tumor islands was associated with neck node metastasis, and the expression of CLDN4 was associated with higher histological grade, and tumor recurrence. Membranous staining for CLDN4 in tumor cells, and weak intensity of CLDN4 immunoexpression were predictive for poorer survival. In a multivariate analysis for disease recurrence, CLDN1 immunostaining was statistically significant. Specifically, CDLN1 expression in the tumor invasive front was associated with tumor recurrence. Our results indicate that CLDN4 expression is correlated with poor prognosis, and CLDN1 expression may be an indicator of recurrence of OSCC.

Vemurafenib-associated neutrophilic panniculitis: An emergent adverse effect of variable severity.

Vemurafenib is a selective BRAF kinase inhibitor recently proven to improve rates of overall and progression-free survival in patients with BRAF-V600-mutant metastatic melanoma. The most common adverse effects of this targeted therapy are arthralgia, fatigue, and cutaneous lesions, including alopecia, photosensitivity, pruritus, hand-foot skin reactions, squamous cell carcinomas, keratoacanthomas, warty dyskeratomas and verrucous keratosis. Less frequently, cases of panniculitis of varying severity have been reported in patients receiving vemurafenib. In this report, we describe a patient who developed asymptomatic nodules on her legs, with complete, spontaneous resolution, while on vemurafenib therapy. A causal relationship was considered likely because of the timing of occurrence and the absence of other potential causes after extensive assessment. Vemurafenib therapy was continued at full dosage and no recurrences were observed. We believe that management of lobular panniculitis associated with selective BRAF inhibitors should vary according to the clinical presentation, degree of systemic involvement, and presence of joint inflammation. Physicians should be aware of this emergent side effect. Treatment discontinuation should be considered on a case-by-case basis because the condition may resolve spontaneously.

Medullary thyroid carcinoma and 2q37 deletion in a patient with nevoid basal cell carcinoma syndrome: clinical description and genetic analysis.

BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS) is a rare, inheritable, multisystem disorder characterized by numerous basal cell carcinomas (BCCs), maxillary keratocyst, and musculoskeletal malformations. Occasionally, it is associated with malignancies like rhabdomyoma, melanoma, and sinonasal undifferentiated carcinoma, to name a few. METHODS: A patient presented with NBCCS with a medullary thyroid carcinoma. Clinical, surgical details, and germline genetic analysis are herein described. RESULTS: A 32-year-old woman was referred to our department with suspicion of medullary thyroid carcinoma, which was confirmed by histopathological examination. The patient was diagnosed as also having NBCCS. Germline mutation analysis indicated wild-type genes PTCH1 and RET. DNA copy number analysis by high resolution microarray comparative genomic hybridization (CGH) revealed a small interstitial loss at chromosomal band 2q37.3. CONCLUSION: To our knowledge, this is the first described patient with NBCCS carrying a medullary thyroid carcinoma and a 2q37 deletion, which confirms that this syndrome can be associated with many different malignancies.

Intestinal-type sinonasal adenocarcinomas. Immunohistochemical profile of 66 cases.

INTRODUCTION AND OBJECTIVES: Intestinal-type sinonasal adenocarcinomas are malignant epithelial tumours. Around 8-25% of all sinonasal malignant tumours are intestinal-type adenocarcinomas, which are related to wood dust exposure. Four histological subtypes have been described: papillary, colonic, solid and mucinous. We performed a pathological and immunohistochemical study in order to describe characteristics with prognostic, diagnostic and therapeutic value, and also to compare our results with previous studies. METHODS: Sixty six tumour samples were analysed and protein expression of p53, p16, E-cadherin, ß-catenin, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2/neu) and cyclooxygenase-2 (COX-2) was performed by tissue microarray blocks. RESULTS: The 63% of cases were p53 positive; 37% showed nuclear staining with ß-catenin and 100% with E-cadherin, while 98% showed membrane staining with ß-catenin, 7% with EGFR, 8% with HER2/neu and 52% with COX-2; and 59% of the cases lost p16 expression. CONCLUSIONS: Intracranial invasion was the worst prognostic associated event. Solid and mucinous tumours were the most aggressive histological subtypes. Intracranial invasion was more frequent in mucinous subtype tumours. Immunohistochemical results were similar in all tumour subtypes, except for mucinous tumours, which showed weak expression of E-cadherin and ß-catenin. Comparing with previous studies, we found a lower expression of EGFR, HER2/neu and COX-2. The p16 expression was associated with worse survival and metastatic disease.

Cutaneous collagenous vasculopathy: description of two new cases in elderly women and review of the literature.

Cutaneous collagenous vasculopathy (CCV) is an idiopathic microangiopathy with characteristic histological findings. It was described in 2000, and 9 cases have since been described. Two women of 83 and 74 years consulted for long-standing telangiectasias. In case 1, they affected the limbs and trunk and in case 2 were located on the legs. Biopsies of these lesions showed dilated vascular structures whose walls were thickened due to deposition of eosinophilic hyaline material. The affected vessels were located in the superficial dermis in case 1, and in case 2 the reticular dermis was also affected. CCV is a microangiopathy of unknown etiology. Clinically it is indistinguishable from generalized essential telangiectasia and differs in its histology. CCV may be underdiagnosed, and some nonbiopsied cases of generalized essential telangiectasia may really be CCV. We contribute 2 new cases of this entity to help establish its clinical and epidemiological characteristics and make its etiology better known.

Multifocal papillary thyroid carcinoma associated with primary amyloid goiter.

Amyloid goiter is a rare condition characterized by a diffuse enlargement of the thyroid gland due to amyloid deposition. Extremely uncommon is the development of differentiated carcinomas within this type of lesion. We describe to our knowledge the sixth case of a papillary thyroid carcinoma within an amyloid goiter, arising in a 45-year old woman with chronic renal failure due to primary amyloidosis. This is the first case of a multifocal papillary carcinoma within an amyloid goiter which produces compressive symptoms. The patient suffered a total thyroidectomy with the histological diagnosis of amyloid goiter with a multifocal papillary carcinoma of follicular variant. The Congo red stain confirmed the diagnosis of amyloid goiter. Two years and a half after the surgery the patient is free of recurrence. Amyloid goiter can hide a differentiated carcinoma. To diagnose and early treat this pathology, the knowledge of the possible association between an amyloid goiter and a differentiated carcinoma is needed.