Naso-ethmoidal phosphaturic mesenchymal tumor: a rare tumor site for an uncommon paraneoplastic syndrome

Mesenchymal Phosphaturic Tumors (MPTs) are the most common cause of an uncommon paraneoplastic syndrome known as Tumor Induced Osteomalacia (TIO). They typically occur in soft tissues and bone and in less than 5% in the head and neck region where the naso-ethmoidal is rarely involved. The presentation of the case includes also the analysis of the expression by RT-PCR of two “phosphatonins” that are known to be involved in the development of the syndrome. For the rarity of MPTs in the head and neck, otolaryngologists and maxillofacial surgeons might not be familiar with these tumors and with TIO whose knowledge is mandatory for the appropriate clinical work-up and treatment of the affected patients

Design of a regulated lentiviral vector for hematopoietic stem cell gene therapy of globoid cell leukodystrophy

Globoid cell leukodystrophy (GLD) is a demyelinating lysosomal storage disease due to the deficiency of the galactocerebrosidase (GALC) enzyme. The favorable outcome of hematopoietic stem and progenitor cell (HSPC)-based approaches in GLD and other similar diseases suggests HSPC gene therapy as a promising therapeutic option for patients. The path to clinical development of this strategy was hampered by a selective toxicity of the overexpressed GALC in the HSPC compartment. Here, we presented the optimization of a lentiviral vector (LV) in which miR-126 regulation was coupled to codon optimization of the human GALC cDNA to obtain a selective and enhanced enzymatic activity only upon transduced HSPCs differentiation. The safety of human GALC overexpression driven by this LV was extensively demonstrated in vitro and in vivo on human HSPCs from healthy donors. No perturbation in the content of proapoptotic sphingolipids, gene expression profile, and capability of engraftment and mutlilineage differentiation in chimeric mice was observed. The therapeutic potential of this LV was then assessed in a severe GLD murine model that benefited from transplantation of corrected HSPCs with longer survival and ameliorated phenotype as compared to untreated siblings. This construct has thus been selected as a candidate for clinical translatio

Desmoplastic Melanoma: Report of 5 Cases

Background. The clinical presentation of desmoplastic melanoma is often challenging. We report the experience of the Melanoma Unit of Spedali Civili University Hospital of Brescia, Italy. Method. Study subjects were drawn from 1770 patients with histologica confirmed melanoma. Within this group, desmoplastic melanoma developed in 5 patients. For each diagnosed melanoma, histological characteristics, treatment, and outcomes were evaluated. Results. Of the 5 patients described in this study, 2 were males and 3 females. The average age was 62.4 years ranging from 56 to 68 years. Breslow thickness ranged from 2.1 to 12 mm with a mean thickness of 5.8 mm. Primary treatment of 5 patients included a wide local excision of their primary lesions. Conclusions. Desmoplastic melanoma is a rare neoplasm which clinically may mimic other tumours or cutaneous infiltrate of uncertain significance. The diagnosis is hiastopathological and radical resection is necessary

The physical effects of wearing personal protective equipment: a scoping review

Background: The COVID-19 pandemic has required healthcare workers to wear personal protective equipment (PPE), and although there is increasing awareness of the physical effects of wearing PPE, the literature has yet to be synthesised around this topic. Methods: A scoping review was conducted to synthesise existing literature on the physical effects of wearing PPE and identify gaps in the literature. A comprehensive search strategy was undertaken using five databases from 1995 to July 2020. Results: A total of 375 relevant articles were identified and screened. Twenty-three studies were included in this review. Studies were conducted across 10 countries, spanning 16 years from 2004 to 2020. Half (13/23) were randomised controlled trials or quasi-experimental studies, five surveys, two qualitative studies, two observational or case series and one Delphi study. Most (82%, 19/23) studies involved the N95 mask (either valved or unvalved). None specifically studied the filtering facepiece 3 mask. The main physical effects relate to skin irritation, pressure ulcers, fatigue, increased breathing resistance, increased carbon dioxide rebreathing, heat around the face, impaired communication and wearer reported discomfort. Few studies examined the impact of prolonged wear (akin to real life practice) on the physical effects, and different types of PPE had different effects. Conclusions: The physical effects of wearing PPE are not insignificant. Few studies examined the physiological impact of wearing respiratory protective devices for prolonged periods whilst conducting usual nursing activity. No ideal respirators for healthcare workers exist, and the development of more ergonomic designs of PPE is required

Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with T2 to T4, N0 and N1 breast cancer

Abstract Background Histological status of axillary lymph nodes is an important prognostic factor in patients receiving surgery for breast cancer (BC). Sentinel lymph node (SLN) biopsy (B) has rapidly replaced axillary lymph node dissection (ALND), and is now the standard of care for axillary staging in patients with clinically node-negative (N0) operable BC. The aim of this study is to compare pretreatment lymphoscintigraphy with a post primary systemic treatment (PST) scan in order to reduce the false-negative rates for SLNB. Methods In this single-institution study we considered 170 consecutive T2-4 N0-1 M0 BC patients treated with anthracycline-based PST. At the time of incisional biopsy, we performed sentinel lymphatic mapping. After PST, all patients repeated lymphoscintigraphy with the same methodology. During definitive surgery we performed further sentinel lymphatic mapping, SLNB and ALND. Results The SLN was removed in 158/170 patients giving an identification rate of 92.9% (95% confidence interval (CI) = 88.0–96.3%) and a false-negative rate of 14.0% (95% CI = 6.3–25.8%). SLNB revealed a sensitivity of 86.0% (95% CI = 74.2–93.7%), an accuracy of 94.9% (95% CI = 90.3–97.8%) and a negative predictive value of 92.7% (95% CI = 86.1–96.8%). Conclusion Identification rate, sensitivity and accuracy are in accordance with other studies on SLNB after PST, even after clinically negative node conversion following PST. This study confirms that diagnostic biopsy and neoadjuvant chemotherapy maintain breast lymphatic drainage unaltered

Splenic marginal zone lymphoma: a prognostic model for clinical use.

The Integruppo Italiano Linfomi (IIL) carried out a study to assess the outcomes of splenic marginal zone lymphoma and to identify prognostic factors in 309 patients. The 5-year cause-specific survival (CSS) rate was 76%. In univariate analysis, the parameters predictive of shorter CSS were hemoglobin levels below 12 g/dL (P < .001), albumin levels below 3.5 g/dL (P = .001), International Prognostic Index (IPI) scores of 2 to 3 (P < .001), lactate dehydrogenase (LDH) levels above normal (P < .001), age older than 60 years (P = .01), platelet counts below 100 000/μL (P = .04), HbsAg-positivity (P = .01), and no splenectomy at diagnosis (P = .006). Values that maintained a negative influence on CSS in multivariate analysis were hemoglobin level less than 12 g/dL, LDH level greater than normal, and albumin level less than 3.5 g/dL. Using these 3 variables, we grouped patients into 3 prognostic categories: low-risk group (41%) with no adverse factors, intermediate-risk group (34%) with one adverse factor, and high-risk group (25%) with 2 or 3 adverse factors. The 5-year CSS rate was 88% for the low-risk group, 73% for the intermediate-risk group, and 50% for the high-risk group. The cause-specific mortality rate (x 1000 person-years) was 20 for the low-risk group, 47 for the intermediate-risk group, and 174 for the high-risk group. This latter group accounted for 54% of all lymphoma-related deaths. In conclusion, with the use of readily available factors, this prognostic index may be an effective tool for evaluating the need for treatment and the intensity of therapy in an individual patient. © 2006 by The American Society of Hematology

Anthracycline-based chemotherapy as primary treatment for intravascular lymphoma

Background: Optimal therapeutic management of intravascular lymphoma (IVL) lacks precise guidelines. Patients and methods: The clinico-pathological features of 38 HIV-negative patients with IVL were reviewed to define efficacy of chemotherapy in these malignancies. Clinical characteristics of 22 patients treated with chemotherapy and of 16 untreated patients were compared in order to understand better the impact and causes of potential patient selection. Results: Median age was 70 years (range 34-90), with a male/female ratio of 0.9; 23 (61%) patients had Eastern Cooperative Oncology Group performance status (ECOG-PS) >1; 21 (55%) had systemic symptoms. Cutaneous lesions and anemia were significantly more common among patients treated with chemotherapy; central nervous system (CNS) and renal involvement were significantly more common among untreated patients. Chemotherapy was associated with a response rate of 59% and a 3-year overall survival of 33 \ub1 11%. Five of six patients with CNS involvement received chemotherapy: four of them died early; only one patient, treated with adriamycin, cyclophosphamide, vincristine, methotrexate, bleomycin and prednisolone (MACOP-B) followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), was alive at 19 months. High-dose chemotherapy supported by ASCT was indicated at diagnosis in another patient (43 years of age, stage I), who was alive at 71 months, and at relapse after cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) in two patients who died early after transplantation. PS 641, disease limited to the skin, stage I, and use of chemotherapy were independently associated with better outcome. Conclusions: Anthracycline-based chemotherapy is the standard treatment for IVL. However, survival is disappointing, with a relevant impact of diagnostic delay and lethal complications. More intensive combinations, containing drugs with higher CNS bioavailability, are needed in cases with brain involvement, and the role of high-dose chemotherapy supported by ASCT should be further investigated in younger patients with unfavorable features