Advanced chondrosarcoma of the pelvis: A rare case of urinary obstruction.

Chondrosarcoma is the second most common malignant tumor of the bone with an incidence of 1 in 200.000 per year. Axial skeleton is frequently involved showing poorer oncological outcomes than appendicular one: human pelvis is a site predilection. It is rarely associated to urinary obstruction but according to its localization, it can be frequently linked to compression of pelvic organs as bladder, prostate or bowel. We describe the case of a 52 years old caucasian male with history of advanced pelvic chondrosarcoma and severe hydronephrosis due to total bladder dislocation.

Toxic effects of expanded ataxin-1 involve mechanical instability of the nuclear membrane.

Ataxin 1 (ATXN1) is the protein involved in spinocerebellar ataxia type 1, one of nine dominantly inherited neurodegenerative diseases triggered by polyglutamine expansion. One of the isolated polyglutamine tracts properties is to interact with lipid bilayers. Here we used a multidisciplinary approach to test whether one of the mechanisms responsible for neuronal degeneration involves the destabilization of the nuclear membrane. We thus analyzed the interaction between ATXN1 and lipid membranes, both on cellular models and on artificial lipid bilayers, comparing pathological expanded polyglutamine and histidine interrupted non-harmful polyglutamine tracts of the same length. The toxicity of the different constructs was tested in transiently transfected COS1 cells. Cells expressing pathological ATXN1 presented a significantly higher frequency of anomalous nuclei with respect to those expressing non-harmful ATXN1. Immunofluorescence and electron microscopy showed severe damage in the nuclear membrane of cells expressing the pathological protein. Atomic force microscopy on artificial membranes containing interrupted and non-interrupted partial ATXN1 peptides revealed a different arrangement of the peptides within the lipid bilayer. Force-distance measurements indicated that membrane fragility increases with the lengthening of the uninterrupted glutamine. Transmembrane electrical measurements were performed on artificial bilayers and on the inner nuclear membrane of ATXN1 full length transfected cells. Both artificial lipid bilayers and cellular models demonstrated the dynamic appearance of ionic pathways. Uninterrupted polyglutamines showed not only a larger ionic flow, but also an increase in the single event conductance. Collectively, our results suggest that expanded ATXN1 may induce unregulated ionic pathways in the nuclear membrane, causing severe damage to the cell.

Anti-phospholipids antibodies and immune complexes in COVID-19 patients: a putative role in disease course for anti-annexin-V antibodies.

INTRODUCTION: Besides distinctive respiratory and digestive hallmarks, COVID-19 has been recently associated with a high prevalence of pro-inflammatory and hypercoagulable states known as "COVID-19 Associated Coagulopathy" (CAC), corresponding to a worsening in patients' conditions, whose causes are still to be elucidated. A link between anti-phospholipid antibodies (aPLs) and viral infections has long been suggested. APLs are assessed for anti-phospholipid syndrome (APS) diagnosis, characterized by thrombocytopenia, thrombosis, and coagulopathy. Furthermore, circulating immune complexes (CICs), arisen upon inflammatory responses and related immune dysregulation, can lead to endothelial cell damage and thrombotic complications. METHOD: We performed an extended panel including IgG/IgM anti-cardiolipin, IgG/IgM anti-ß2-glycoprotein-1, coupled with IgG/IgM anti-prothrombin, IgG/IgM anti-annexin-V on two COVID-19 patient groups (early and late infection time), and a negative control group. IgG CIC analysis followed to evaluate inflammatory status, through a possible complement system activation. RESULTS: Our results showed low positive case percentage in IgG/IgM anti-cardiolipin and IgG/IgM anti-ß2-glycoprotein-1 assays (4.54%, 6.25%, and 4.55%; in early infection group, late infection group, and control group, respectively); few positive cases in IgG/IgM anti-prothrombin and IgG/IgM anti-annexin-V immunoassays; and no IgG CIC positivity in any patient. CONCLUSIONS: In conclusion, our data show a low aPL prevalence, likely excluding an involvement in the pathogenesis of CAC. Interestingly, IgG/IgM anti-prothrombin and anti-annexin-V positive cases, detected in late infection group, suggest that aPLs could temporarily increase or could trigger a "COVID-19-induced-APS-like-syndrome" in predisposed patients. Key Points • To our knowledge, anti-prothrombin (aPT) antibodies, anti-annexin-V antibodies and CICs in COVID-19 patients have not been reported in the scientific literature. • Lack of uniformity and the low percentage of aCL/aß2GP1 positivity preclude a putative role in CAC pathogenesis. • IgG/IgM anti-prothrombin and IgG/IgM anti-annexin-V data show that distribution of positive case number increases in late infection patients, significantly in anti-annexin-V results, suggesting a possible role for these anti-phospholipid antibodies in disease course. • aPLs can arise transiently in some patients with critical illness and SARS-CoV-2 infection (disappearing in a few weeks), as well as in other genetically predisposed patients; they could trigger a "COVID-19-induced-APS-like-syndrome".

Primary small-cell neuroendocrine carcinoma of the bladder: Case report and literature review.

BACKGROUND: Neuroendocrine tumours (NET) are extremely rare and aggressive. Although they commonly affect intestine, many organs may be involved such as pancreas, lung or urinary tract. Bladder is rarely involved. Actually, two main forms of bladder NET have been described: small-cell and large-cell. The first one is considered highly agressive since it shows poor oncologic outcomes being mainly diagnosed at advanced stage: the second one is extremely rare and equally aggressive. CASE REPORT: A 78-years-old Caucasian male presented to our facility for lower urinary tract symptoms and gross hematuria recently occurred. He was a strong smoker since many years. No familiarity for urothelial cancer was referred nor previous episodes of hematuria until that time. Citology was negative; outpatient ultrasound of the bladder revealed a 3 cm bladder thickening highly suspicious for bladder cancer; patient underwent TC scan that confirmed the bladder lesion. A transurethral resection of the bladder (TURB) was performed. After 3 months total body TC showed multiple visceral metastases also involving brain and lymph nodes. Best supportive care was offered but the patient died 6 months later. RESULTS: Pathology revealed a mixed bladder tumor: 30% of the specimen resulted as an high-grade urothelial cancer (G3) and 70% as small-cell neuroendocrine variant.Microscopic muscle involvement was excluded. CONCLUSIONS: Neuroendocrine tumors are uncommon entities which origin from cells of neuro-endocrine system and may potentially involve all human tissues. Neuroendocrine smallcell carcinoma of the bladder is a non-urothelial histotype: it is highly aggressive and diagnosed mainly at advanced stages. Whenever considering the high risk of metastatic spread and the poor prognosis, a multimodal approach is highly suggested. TURB alone is uneffective in disease control due to its aggressive nature. Unless metastatic, radical cystectomy and adjuvant chemotherapy represent the gold standard.

Fatal infections in andrology. Atypical clinical presentation of a Fournier's disease.

BACKGROUND: Fournier disease (FD) is a worrisome infection of genital area caused by a polimicrobial infection and characterized by a rapid progression to necrosis. Scrotum, perineum and lower abdomen represent the primary sites of origin. Clinical presentation and laboratory strongly suggest FD, but if not precociously diagnosed, it may quickly evolve into septic syndrome and patient's death. CASE REPORT: A 62 years old Caucasian male presented for fever and penile gross oedema recently occurred. No history of previous urinary tract infection, hematuria or genital trauma was referred. He did not complain any storage or voiding low urinary tract symptom (LUTS); no foci of infection in genitoperineal area was observed nor urethral discharge. The ultrasound (US) revealed a disomogeneous broad thickening of subcutaneous tissues with increased vascularity on Color-Doppler. When the penis was manipulated in order to reduce oedema, retract foreskin and evaluate the glans, clinical parametres rapidly worsened and the patient developed a septic shock with blood pressure falling down, dyspnoea and tachyarrhythmia, and he was fastly sent to Intensive Care Unit where it has been hemodynamically stabilized and subjected to antibiotic therapy. Considering the clinical absence of gangrene's foci, we opted for a conservative treatment by maintaining bladder catheter and drug therapy.