The role of tendon and subacromial bursa in rotator cuff tear pain. A clinical and histopathological study

To evaluate a possible association of shoulder pain with the clinical features and the histopathological changes occurring in the ruptured tendon and subacromial bursa of patients with rotator cuff tear

Osteochondroma as a cause of scapular winging in an adolescent: a case report and review of the literature

INTRODUCTION: Winged scapula is defined as the prominence of the medial border of the scapula. The classic etiopathology of scapular winging are injuries to the spinal accessory or long thoracic nerves resulting respectively in trapezius and serratus anterior palsy. To the best of our knowledge, there are only few reports of scapular lesions being mistaken for winging of the scapula. We report a rare case of a large scapular osteochondroma arising from the medial border and causing a pseudowinging of the scapula. CASE PRESENTATION: A 17-year-old Caucasian boy came to us complaining about a winged left scapula. The patient had a complete painless range of motion, but a large hard bony swelling was palpable along the medial border of his left scapula. A grating sensation was felt when his arm was passively abducted and/or elevated causing discomfort. A lesion revealed on X-rays was diagnosed as an osteochondroma of the medial border of his scapula. After preoperative examinations, he underwent open surgery in order to remove the lesion. A histological examination confirmed the clinical diagnosis of osteochondroma. A clinical examination 3 months later showed a full and painless range of motion, the absence of the grating sensation during passive abduction and elevation and the complete disappearance of his left shoulder deformity. After 2 years of follow-up, there were no clinical or radiological signs of recurrence. CONCLUSIONS: Despite its rarity osteochondroma should be considered in the differential diagnosis for any adolescent presenting with a winging of the scapula

Anti-BCMA novel therapies for multiple myeloma

Recent advances in multiple myeloma therapy have increased the depth of response and ultimately survivals; however, the prognosis remains poor. The BCMA antigen is highly expressed in myeloma cells, thus representing a target for novel therapies. Several agents that target BCMA through different mechanisms, including bispecific T cell engagers drug conjugated to antibody and CAR-T cells, are now available or under development. Immunotherapies targeting BCMA have shown good results in efficacy and safety in multiple myeloma patients previously treated with several lines of therapy. This review will discuss the recent development of anti-BCMA targeted treatments in myeloma, with a special focus on currently available agents

A case of acquired factor XIII deficiency secondary to plasmablastic lymphoma

Acquired factor XIII (FXIII) deficiency is an extremely rare and potentially fatal bleeding disorder. Immune-mediated FXIII deficiency is due to the development of anti-FXIII autoantibodies which may develop with concomitant conditions that cause immune dysregulation such as malignancies or autoimmune disorders. Clinical presentation includes delayed post-operative bleeding or spontaneous soft tissue hematomas and/or cerebral bleeding. Since screening coagulation laboratory tests (prothrombin time, activated partial thromboplastin time, and fibrinogen) are typically normal, acquired FXIII deficiency is likely to be overlooked and underdiagnosed. The management of immune-mediated FXIII deficiency is based on hemostatic therapy, autoantibody removal and eradication of the underlying etiology; however, no treatment guidelines are still available. Here we report a case of acquired FXIII deficiency associated with plasmablastic lymphoma, in order to raise awareness of this rare bleeding disorder and consent prompt life-saving management

Primary systemic treatment and concomitant low dose radiotherapy for breast cancer: final results of a prospective phase II study.

Abstract Background To evaluate the efficacy of preoperative low dose fractionated radiotherapy (LD-FRT) and chemotherapy in breast cancer. Materials and methods Patients with stage IIA–IIIA breast cancer, received LD-FRT (0.40 Gy bid, on day 1 and 2, for 6 cycles) to primary tumor volume and concurrent chemotherapy with non-pegylated liposomal anthracycline and docetaxel. Pathological response was assessed by Mandard Tumor Regression Grade (TRG). We evaluated the pathological major response rate (PMRR) as TRG1 and TRG2. The expected outcome was a PMRR of 60%. The accrual was determined by the single proportion powered analysis ( α = 0.05, power = 0.8). Results Twentyone patients were enrolled. No grade 2–4 acute skin and hematological toxicity was observed. TRG1 was obtained in 3 patients (14.3%), TRG2 in 4 patients (19%). The PMRR was 33.3%; it does not concur with the expected result, but is similar to that of chemotherapy alone. According to molecular subtype, 2/11 luminal A patients and 4/6 luminal B patients obtained a PMRR to preoperative treatment (35.3%); 1/4 basal like patients reported TRG1 (25%). Conclusions LD-FRT concomitant with primary systemic treatment has a good toxicity profile. The response rate is consistent with that of chemotherapy alone, and suggests different interactions between low dose radiotherapy and molecular subtypes. Additional investigations are planned

Safety of COVID-19 mRNA vaccination in patients with history of acquired hemophilia A: a case series

Coronavirus disease 2019 (COVID-19) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection called for a specific and massive vaccination campaign. Acquired hemophilia A (AHA) is a potential life-threatening coagulopathy. Hematological- targeted autoimmune conditions including immune thrombocytopenia, vaccine-induced thrombotic thrombocytopenia and AHA emerged during large-scale vaccination against SARS-CoV-2 and contributed to vaccination hesitation. The aim of the present study was to evaluate the putative recurrence of AHA after vaccination against SARS-CoV-2 with mRNA vaccines (BNT162b2 and mRNA- 1273) in patients with relatively recent history of AHA. Thirteen patients (8 women and 5 men, mean age = 63.1±16.6 years) with AHA in the previous two-to-five years were enrolled in the study. Platelet count, prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen and Factor VIII levels were evaluated 48 hours prior to each vaccine dose and 10 days post-vaccination. Clinical self-assessment and remote video visits were performed in the presence of even minor hemorrhagic signs. No major bleeding events were detected at any time-point, including evaluation at 30 days after the 3rd vaccine dose. No significant hemorrhagic changes were observed, in particular no thrombocytopenia and/or significant alterations in PTT and Factor VIII emerged across subjects. Patients with a previous history of AHA of various etiology do not seem to have an increased recurrence risk after a COVID-19 vaccination course of 3 doses with either mRNA vaccine. This finding supports this specific safety aspect in the face of the possible continuation of the vaccination campaign based on the trend of the COVID-19 pandemic

Melanocyte Colonization and Pigmentation of Breast Carcinoma: Description of Two Pathological Cases and Review of Literature

Colonization of breast carcinoma by non-neoplastic melanocytes of epidermal origin was first described by Azzopardi and Eusebi in 1977. We herein report two cases on the exceptional clinical and pathological features of this phenomenon in a 66-year-old and a 51-year-old patients. The pathogenesis is not fully understood, but a disrupted basement membrane and the role of tumoral growth factors are considered essential

Narcolepsy is a common phenotype in HSAN IE and ADCA-DN

We report on the extensive phenotypic characterization of five Italian patients from four unrelated families carrying dominant heterozygous DNMT1 mutations linked to two distinct autosomal dominant diseases: hereditary sensory and autonomic neuropathy with dementia and hearing loss type IE (HSAN IE) and autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN). Patients underwent genetic analysis of DNMT1 gene, neurophysiological tests investigating sleep, auditory functions and peripheral nervous system, ophthalmological studies including optical coherence tomography, lymphoscintigraphy, brain magnetic resonance and nuclear imaging, cerebrospinal fluid hypocretin-1, total tau, phosphorylated tau, amyloid-β1-42 and 14-3-3 proteins measurement, skin, muscular and sural nerve biopsies. Exome and direct sequencing studies disclosed two different point mutations affecting exon 21 of DNMT1 gene in patients with ADCA-DN, a novel heterozygous point mutation in exon 20 in two affected HSAN IE siblings, and a trinucleotide deletion in exon 20 in the latter patient with HSAN IE. Phenotypic characterization pinpoints that ADCA-DN and HSAN IE represent two discrete clinical entities belonging to the same disease spectrum, with variable degree of overlap. Remarkably, narcolepsy with or without cataplexy with low/intermediate or normal cerebrospinal fluid hypocretin-1 is present in both diseases. The human leukocyte antigen DQB1*06:02 was absent in all patients. Other common symptoms and features observed in our cases, involving the central and peripheral nervous system, include deafness, optic neuropathy-previously not reported in HSAN IE-large and small fibres polyneuropathy and lower limbs oedema. Overall, the two syndromes share more characteristics than previously recognized and narcolepsy is common to both. HSAN IE and ADCA-DN are two extreme phenotypic manifestations of a DNMT1 methylopathy

Increased CD8+ T cell responses to apoptotic T cell-associated antigens in multiple sclerosis.

BACKGROUND: Here, we evaluated the hypothesis that CD8(+) T cell responses to caspase-cleaved antigens derived from effector T cells undergoing apoptosis, may contribute to multiple sclerosis (MS) immunopathology. METHODS: The percentage of autoreactive CD8(+) T effector cells specific for various apoptotic T cell-associated self-epitopes (apoptotic epitopes) were detected in the peripheral blood and cerebrospinal fluid (CSF) by both enzyme-linked immunospot and dextramers of class I molecules complexed with relevant apoptotic epitopes. Moreover, the capacity of dextramer(+) CD8(+) T cells to produce interferon (IFN)-γ and/or interleukin (IL)-17 in response to the relevant apoptotic epitopes was evaluated by the intracellular cytokine staining. Cross-presentation assay of apoptotic T cells by dendritic cells was also evaluated ex vivo. RESULTS: We found that polyfunctional (IFN-γ and/or IL-17 producing) autoreactive CD8(+) T cells specific for apoptotic epitopes were represented in MS patients with frequencies significantly higher than in healthy donors. These autoreactive CD8(+) T cells with a strong potential to produce IFN-γ or IL-17 in response to the relevant apoptotic epitopes were significantly accumulated in the CSF from the same patients. In addition, the frequencies of these autoreactive CD8(+) T cells correlated with the disease disability. Cross-presentation assay revealed that caspase-cleaved cellular proteins are required to activate apoptotic epitope-specific CD8(+) T cells ex vivo. CONCLUSION: Taken together, these data indicate that apoptotic epitope-specific CD8(+) T cells with strong inflammatory potential are recruited at the level of the inflammatory site, where they may be involved in MS immunopathology through the production of high levels of inflammatory cytokines