Publications by authors named "Giuliana Roselli"

26 Publications

  • Page 1 of 1

Xanthomatous Inflammatory Infiltrate Involving the Spleen: An Unusual Presentation of Erdheim-Chester Disease and Review of the Literature.

Am J Case Rep 2021 Jun 4;22:e931060. Epub 2021 Jun 4.

Pathological Anatomy Section, Careggi University Hospital, Florence, Italy.

BACKGROUND Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis characterized by foamy histiocytes, Touton-like giant cells, and fibrosis, typically affecting the diaphyseal and metaphyseal region of the long bones but that can involve any organ or tissue. ECD is usually associated with the BRAF V600E mutation or with other molecular mutations inserted in the MAPK cascade. CASE REPORT We present the case of a 63-year-old man with a previous history of myocardial infarction who underwent an emergency splenectomy for splenic rupture after an accidental fall. Histological examination of the spleen showed a diffuse xanthogranulomatous proliferation (CD68+, CD163+, S100-, CD1a-) with rare Touton-like giant cells in the red pulp. Based on the histologic findings, a diagnosis of ECD was made. However, skeletal involvement and BRAF V600E mutation were not detected. CONCLUSIONS Cases of non-Langerhans cell histiocytosis that are histologically consistent with ECD in unusual sites have been increasingly described. There is also anecdotal evidence for cases being associated with mutations besides BRAF V600E or with no genetic alteration and no skeletal involvement. Likewise, the spectrum of clinical and molecular features of ECD can be broader than previously considered. Furthermore, there is evidence that various phases of the disease can show different clinical presentations with distinct prognostic impact, according to the mutational spectrum. Recognizing ECD at an early stage allows more effective patient management, and pathologists and clinicians should be aware of the unusual clinical presentations of this rare condition.
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http://dx.doi.org/10.12659/AJCR.931060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183300PMC
June 2021

Physiotherapy after ultrasound-guided percutaneous irrigation in rotator cuff calcific tendinopathy.

J Back Musculoskelet Rehabil 2021 Apr 28. Epub 2021 Apr 28.

Azienda Ospedaliera Universitaria Careggi, Firenze, Italy.

Background: Rotator cuff calcific tendinopathy (RCCT) is a very frequent and debilitating disease often treated with Ultrasound-guided percutaneous irrigation (UGPI) followed by physiotherapy.

Objective: A multicenter observational clinical study was designed to assess the effects of physiotherapy after UGPI on the functional recovery of the shoulders of patients suffering from RCCT.

Method: One hundred sixty-six patients (mean age 50.7± 7.6 years), 121 women, with painful RCCT were treated with UGPI and assessed at the day of UGPI (T0), and at one (T1), 3 (T2) and 6 (T3) months after treatment by the Constant- Murley Score (CMS), Oxford Shoulder Scale (OSS) and Numerical Rating Scale (NRS). Patients were divided into 2 groups, Physiotherapy (PT+) and not Physiotherapy (PT-) according to the performance of the rehabilitation program based on personal decision.

Results: A significant improvement at T1 in all outcomes in both groups and between T1 and T3 for NRS during movement and OSS was found, but not for NRS at rest and CMS. There was no difference between groups for all outcome measures. In 27,1% of patients symptoms recurred in an average of 13 ± 8 weeks.

Conclusions: Results suggest that post-UGPI not-standardized physiotherapy might not provide additional clinical benefits in short and medium term. Further studies could assess the effectiveness of physiotherapy performed after three months in patients with recurrence of pain.
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http://dx.doi.org/10.3233/BMR-191637DOI Listing
April 2021

Dedifferentiated soft tissue leiomyosarcoma with heterologous osteosarcoma component: case report and review of the literature.

Clin Sarcoma Res 2020 5;10. Epub 2020 Apr 5.

1Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy.

Background: Soft tissue dedifferentiated leiomyosarcoma with heterologous osteosarcomatous component is an extremely rare entity described in only few cases in the literature.

Case Presentation: We report the case of a 65-year-old male patient who, after initial inadequate surgery of a tumor of the left forearm, developed local recurrence that was treated with neoadjuvant chemotherapy, surgery and postoperative radiation therapy. Histologically the tumor showed an abrupt separation of two different patterns. One component consisted of interlacing fascicles of spindle cells with cigar-shaped nuclei strongly positive for smooth muscle actin, desmin and H-caldesmon. The other component consisted of a high-grade pleomorphic sarcoma with osteoid and chondroid matrix production, which positive for SATB2. Thus, a final diagnosis of dedifferentiated leiomyosarcoma was rendered. Fifteen months after treatment, the patient presented further local and distant relapse with pulmonary metastases and died 23 months after the first presentation.

Discussion And Conclusions: Dedifferentiated leiomyosarcoma is a highly malignant neoplasm with a poor outcome. Extensive sampling of soft tissue leiomyosarcomas is recommended to detect possible dedifferentiated areas as they represent a crucial prognostic parameter.
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http://dx.doi.org/10.1186/s13569-020-00129-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133003PMC
April 2020

Clinical features, prognostic factors and outcome in a series of 29 extra-skeletal Ewing Sarcoma. Adequate margins and surgery-radiotherapy association improve overall survival.

J Orthop 2020 Sep-Oct;21:236-239. Epub 2020 Mar 25.

Divisione di Ortopedia Oncologica e Ricostruttiva Azienda Ospedaliero Universitaria Careggi Firenze, Italy.

Objective: Authors review a series of 29 extra-skeletal Ewing Sarcoma (EES).

Methods: They analyzed characteristics, prognostic factors and outcome of EES.

Results: Authors report 60% Overall Survival (OS) and 56% of Event Free Survival (EFS) at 5 years. Better 5 years EFS was found in patients with localized disease (68.8%) compared to metastatic EES (33.3%) (p = 0.042). Radiotherapy + surgery offered the best local treatment (p=0.017). Volume (p = 0.032), Surgical margins (p = 0.01), metastatic disease (p = 0.0013) were a significant prognostic factor for OS at 5-yrs.

Conclusion: Adequate margins and surgery+radiotherapy improve Overall Survival.
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http://dx.doi.org/10.1016/j.jor.2020.03.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132112PMC
March 2020

Partial rupture of anterior cruciate ligament: preliminary experience of selective reconstruction.

J Orthop Traumatol 2020 Mar 28;21(1). Epub 2020 Mar 28.

Orthopaedic Clinic CTO, University of Florence, Largo Palagi 1, 50139, Florence, Italy.

Background: Partial lesions of the anterior cruciate ligament (ACL) are more common than is generally thought, accounting for about 10-12% of ACL injuries. Selective reconstruction may be considered as an option in isolated bundle rupture. The purpose of this study is to evaluate both subjective and objective clinical results, as well as functional recovery time, after selective arthroscopic single-bundle reconstruction in a consecutive series of patients affected by partial ACL rupture.

Materials And Methods: Thirty-six patients undergoing selective reconstruction of a single ACL bundle were retrospectively evaluated from a series of 354 ACL reconstructions performed over a 3-year period. Although the suspicion of partial lesions was present at clinical and magnetic resonance imaging (MRI) evaluation, final diagnosis was obtained during arthroscopy. All patients were operated using the same technique and type of fixation, and undergoing the same functional recovery protocol.

Results: Mean follow-up was 64 months (48-84 months). All patients but one achieved good functional recovery and returned to their sports within a mean period of 6.1 months. A single patient complained of postoperative instability 1 year after the index operation and needed further surgery. No complications were recorded.

Conclusions: Selective reconstruction of partial ACL injury is a method to bear in mind because it offers quick functional recovery. Specific technical and diagnostic steps should be performed and discussed with patients preoperatively.

Level Of Evidence: Level 4, retrospective study.
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http://dx.doi.org/10.1186/s10195-020-0544-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103020PMC
March 2020

Total femur prosthesis in oncological and not oncological series. Survival and failures.

J Orthop 2020 Jan-Feb;17:215-220. Epub 2019 Nov 12.

Divisione di Ortopedia Oncologica e Ricostruttiva, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy.

Total femur prosthesis (TFP) can be used in both oncological and prosthetic revision surgery. A retrospective analysis of 32 patients receiving a TFP at a single Center between 2002 and 2018 was performed. The average follow-up was 60 months. Revision implant free survival (RIFS) of the implants was 87% at 5 and 10 years and 72% at 15 years. Overall implant survival (OIS) of the prosthesis was 90% at 5, 10 and 15 years. Complications observed: two soft tissue failures, two infection failure and one tumor progression failure.
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http://dx.doi.org/10.1016/j.jor.2019.11.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928329PMC
November 2019

Long-Term Functional Outcome After Surgical Treatment of Peroneal Intraneural Ganglion Cyst.

World Neurosurg 2019 Dec 5;132:e217-e222. Epub 2019 Sep 5.

Plastic and Reconstructive Microsurgery, Careggi University Hospital, Florence, Italy.

Background: Intraneural ganglia are benign mucinous cystic formations that originate within the epineurium of peripheral nerves. Different treatments have been recommended, with an overall satisfactory outcome. In this paper, we aim to evaluate the long-term outcomes of surgical treatment of peroneal intraneural ganglia by reviewing our local institutional experience.

Methods: We performed a case series review of peroneal intraneural ganglia surgical treatment performed by the senior author. Demographic and surgical details were abstracted from the medical record for each patient. Electrodiagnostic studies and magnetic resonance imaging (MRI) were performed in all patients pre- and postoperatively.

Results: Eight men were enrolled, with an average age at time of surgery of 47.5 years (range 28-68 years). Motor testing revealed a preoperative deficit of dorsiflexion, eversion, and toe extension in 7 patients, with a median preoperative Medical Research Council (MRC) score of 0/5. Sensory loss in the distribution of the common peroneal nerve was present in 7 patients. Mean clinical follow-up time was 113 months (range 32-189 months). Significant pain relief was achieved in all patients. Overall neurologic function was improved, more so for motor function. The median postoperative dorsiflexion, eversion, and toe extension at last follow-up were MRC score of 5/5. No complications occurred postoperatively. There was no clinical evidence of intraneural recurrence, as confirmed in postoperative MRI. In 2 patients, an extraneural cystic formation was visible in the anterior muscular compartment.

Conclusions: The data from our series support excellent long-term postoperative motor outcomes with a low recurrence rate. To avoid extraneural recurrence, resection of the superior tibiofibular joint is necessary.
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http://dx.doi.org/10.1016/j.wneu.2019.08.195DOI Listing
December 2019

Leiomyosarcoma: Clinicopathological study and retrospective analysis of prognostic factors in a series of 100 patients.

J Orthop 2019 Jul-Aug;16(4):303-307. Epub 2019 Mar 25.

Divisione di Ortopedia Oncologica e Ricostruttiva Azienda Ospedaliero Universitaria Careggi Firenze, Italy.

The Authors reported a retrospective study of 100 Leiomyosarcoma (LMS), evaluating factors that may influence Overall Survival (OS), Local Recurrence Free Survival (LRFS), Metastasis Free Survival (MFS). Tumor Size (P = 0,0009), Local Recurrence (P = 0,0487), Distant relapse (P < 0,0001), Type of Presentation (P = 0,0213) were significant risk factors affecting overall survival (OS). Tumor Size (P = 0.024), age at diagnosis (P = 0,0086), type of presentation (P < 0,0001) and Local Recurrence (P = 0.0152) affected metastasis free survival (MFS). Type of presentation (P = 0,001) was an independent prognostic factor of local recurrence-free survival (LRFS).
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http://dx.doi.org/10.1016/j.jor.2019.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441716PMC
March 2019

Multimodal Treatment in Pelvic Ewing Sarcoma: A Prognostic Factor Analysis.

Surg Technol Int 2019 May;34:489-496

Department of Orthopaedic Oncology and Reconstructive Surgery, University of Florence, Azienda Ospedaliera Universitaria Careggi, Florence, Italy.

Background: Although multidisciplinary therapies have improved local control and overall survival in Ewing sarcoma (ES), the prognosis of pelvic lesions remains markedly worse than that of limb ES.

Methods: We retrospectively evaluated the influence of the type of local treatment, margins, necrosis and sacrum involvement on overall survival (OS) and disease-free survival (DFS) in a series of 21 non-metastatic pelvic ES.

Results: The average follow-up was 46.3 months (range 3-156). Only one patient had recurrence, at 11 months after surgery. Eight patients showed pulmonary metastasis and five showed bone metastases. Necrosis was the only significant prognostic factor for overall survival at 5 years (p=0.0132) and disease-free survival (p=0.0086). Overall survival at 5 years was 40.1%.

Conclusion: Local control in pelvic Ewing sarcoma is comparable for patients treated with surgery (S), surgery plus radiotherapy (S/RT), or definitive radiotherapy (RT). The combination of surgery plus radiotherapy could be indicated in cases of large tumor, a poor necrosis response (< 90%), or an inadequate margin with involvement of the sacrum. A poor response to neoadjuvant therapy is a significant risk factor for both local control and overall survival.
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May 2019

Preoperative Denosumab With Curettage and Cryotherapy in Giant Cell Tumor of Bone: Is There an Increased Risk of Local Recurrence?

Clin Orthop Relat Res 2018 09;476(9):1783-1790

G. Scoccianti, F. Totti, M. Scorianz, D. A. Campanacci, Department of Orthopaedic Oncology and Reconstructive Surgery, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy G. Baldi, Department of Medical Oncology, Hospital of Prato, Prato, Italy G. Roselli, Department of Radiology, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy G. Beltrami, Department of Paediatric Orthopaedic Oncology, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy A. Franchi, Department of Translational Research and New Technologies, Department of Anatomic Pathology, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy R. Capanna, Department of Orthopaedics and Traumatology, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.

Background: Denosumab is a monoclonal RANKL antibody, which was originally introduced for the treatment of osteoporosis and bone metastases from solid tumors, but more recently has been used for treatment of giant cell tumor of bone (GCTB). In GCTB, denosumab has been used as a single agent in patients with inoperable tumors; it also has been used before surgery in some patients with the aim to downstage the tumor to facilitate a joint-preserving procedure (curettage) rather than a resection. However, few studies are available evaluating the benefits and risks of denosumab for the latter indication.

Questions/purposes: (1) Does preoperative treatment with denosumab reduce the risk of local recurrence in patients treated for GCTB? (2) Are there adverse effects of short-term denosumab use before surgery and, if so, what are they?

Methods: All patients with a diagnosis of GCTB surgically treated at our institution from June 2009 to June 2016 with curettage and cryotherapy were retrospectively evaluated to compare patients treated with curettage alone versus patients treated with curettage after preoperative therapy with denosumab. During that period, we treated 97 patients for GCTB; 30 patients were excluded because they received a resection; 34 patients were excluded because they received curettage without cryotherapy. Of the remaining 33 patients, four were excluded because they received denosumab only after surgery, one because she received zoledronic acid, one because she received a curettage after her refusal of a resection that was the advised procedure, two because they were lost to followup early, and four because they were treated for recurrence rather than a new diagnosis of GCTB. The remaining 21 patients were included. Twelve lesions had been treated with surgery after denosumab and nine with surgery alone. During the study period, we preferentially used denosumab for the more aggressive-looking lesions. After curettage, cryotherapy of the residual bone walls was performed with argon cryoprobes to -150° C after pouring gel into the cavity, and we then used cement (17 patients) or morcellized allograft (four patients). Tumors were Campanacci Grade 3 in eight of 12 patients in the denosumab group and in two of nine patients in the surgery-only group (p = 0.08), but the extent of epiphyseal juxtaarticular bone involvement was not different between the groups with the numbers available. Median followup was 39 months (range, 14-55 months) in the denosumab group and 27 months (range, 18-92 months) in the surgery-only group. We used chart review to record the proportion of patients in each treatment group who had a local recurrence and to tally adverse events.

Results: With the numbers available, there was no difference in the proportion of patients experiencing a recurrence (five of 12 in the denosumab group and one of nine in the surgery-only group; p = 0.18). We found no adverse effects associated with denosumab either during or after treatment; specifically, we found no alterations in electrolyte levels, blood count, or liver and renal function parameters. In this small series, no patient has developed osteonecrosis of the jaw.

Conclusions: In this small series, use of denosumab before surgery for GCTB appeared to allow the reforming of a bone peripheral rim around the tumor, perhaps facilitating curettage rather than osteoarticular resection in some patients. However, we did not observe a decrease in the risk of local recurrence with the use of denosumab, suggesting that it may not decrease the aggressiveness of the disease; according to our preliminary results, we cannot exclude that the rate of local recurrence could be even higher after curettage in denosumab-treated patients than in nontreated patients, and until or unless larger studies demonstrate such a reduction, primary intralesional surgery without denosumab seems more prudent when curettage is feasible at presentation. We did not observe any adverse effects with denosumab, but we caution readers that this study was underpowered to detect even relatively common complications and relatively large differences in the risk of local recurrence. Future studies should evaluate denosumab prospectively; given the relative rarity of this tumor, we suspect multicenter studies are needed to achieve this.

Level Of Evidence: Level III, therapeutic study.
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http://dx.doi.org/10.1007/s11999.0000000000000104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6259811PMC
September 2018

Liposarcoma: Clinico-pathological analysis, prognostic factors and survival in a series of 307 patients treated at a single institution.

J Orthop Sci 2018 Nov 11;23(6):1038-1044. Epub 2018 Jul 11.

Azienda Ospedaliera Universitaria Careggi Firenze, Ortopedia Oncologica e Ricostruttiva, Firenze, Italy.

Background And Objectives: Liposarcoma (LPS) is a malignant mesenchymal tumor and the most common soft tissue sarcoma. Four different subtypes are described: well differentiated (WD) LPS or atypical lipomatous tumor (ALT), dedifferentiated (DD) LPS, myxoid LPS, and pleomorphic LPS (PLS). The objective of the study was to investigate prognostic factors and clinical outcome of liposarcoma.

Methods: We retrospectively examined the clinico-pathological features of a series of 307 patients affected by Liposarcoma at a mean follow-up of 69 months (range 6-257). ALT/WD LPS were analyzed separately. The influence of site, size, type of presentation, grading, histotype and local recurrence on local and systemic control and survival was assessed.

Results: The statistical analysis indicated that only surgical margins represented a significant prognostic factor for local recurrence in ALT/WD LPS (P = 0.0007) and other subtypes of LPS (P = 0.0055). In myxoid, PLS and DD LPS, significant prognostic factors for metastasis free survival (MFS) were surgical margins (P = 0.0009), size of the tumor (P = 0.0358), histology (P = 0.0117) and local recurrence (P = 0.0015). In multivariate analysis, surgical margins (0.0180), size (0.0432) and local recurrence (0.0288) correlated independently with MFS. Margins (P = 0.0315), local recurrence (P = 0.0482) and metastases (P < 0.0001) were prognostic factors for overall survival (OS).

Conclusion: Marginal surgery can be an accepted treatment for ALT/WD LPS. In other liposarcoma subtypes (Myxoid, DD, PLS) wide or radical surgery is recommended as the margins significantly influence local recurrence-free survival (LRFS), metastasis-free survival (MFS) and overall survival (OS). Local recurrence and metastases were significant prognostic factors for OS.
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http://dx.doi.org/10.1016/j.jos.2018.06.008DOI Listing
November 2018

Myxoid Liposarcoma: Prognostic Factors and Metastatic Pattern in a Series of 148 Patients Treated at a Single Institution.

Int J Surg Oncol 2018 16;2018:8928706. Epub 2018 May 16.

Divisione di Ortopedia Oncologica e Ricostruttiva Ospedale, Azienda Universitaria Ospedaliera Careggi Firenze, Firenze, Italy.

Objectives: The authors reported a retrospective study on myxoid liposarcomas (MLs), evaluating factors that may influence overall survival (OS), local recurrence-free survival (LRFS), metastasis-free survival (MFS), and analyzing the metastatic pattern.

Methods: 148 MLs were analyzed. The sites of metastases were investigated.

Results: Margins ( = 0.002), grading ( = 0,0479), and metastasis ( < 0,0001) were significant risk factors affecting overall survival (OS). Type of presentation ( = 0.0243), grading ( = 0,0055), margin ( = 0.0001), and local recurrence (0.0437) were risk factors on metastasis-free survival (MFS). Authors did not observe statistically significant risk factors for local recurrence-free survival (LRFS) and reported 55% extrapulmonary metastases and 45% pulmonary metastases.

Conclusion: Margins, grading, presentation, local recurrence, and metastasis were prognostic factors. Extrapulmonary metastases were more frequent in myxoid liposarcoma.
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http://dx.doi.org/10.1155/2018/8928706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011058PMC
June 2019

A Posttraumatic Distal Radius Allograft: 10 Years Follow-Up.

J Wrist Surg 2018 Feb 9;7(1):84-88. Epub 2017 Jun 9.

Hand Surgery and Reconstructive Microsurgery Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.

 Wrist osteoarthritis is a common disease often resulting from malunited fractures of the distal radius. The primary treatment purpose is to provide pain relief, while maintaining strength and mobility whenever possible. In a patient presenting a posttraumatic degeneration of the wrist, deciding which surgical technique, which joints to sacrifice and which to preserve is crucial to optimizing the outcome.  We describe a 10-year follow-up of an osteoarticular allograft of the distal radius proposed to treat an isolated distal radius posttraumatic degeneration. The patient was young and active. No or slight articular degeneration of the carpal rows was present. The surgical technique was based on a periarticular step-cut that allowed the preservation of the dorsal capsule and the maximum contact between the bone and the allograft.  In the literature, the allograft of the radius is described as a solution to an oncologic problem. Considering a posttraumatic scenario other techniques are usually performed. However, compared with artificial interbody fusion devices and prosthetic implants, structural bone allograft retains an advantage in biologic performance. It has osteoconductive properties and is similar to native tissues providing a progressive incorporation by the host.  This surgical technique provide a metaphyseal step-cut able to ensure a secure stabilization and a wide contact surface between the allograft and the native bone. Integration of the allograft with good functional and radiological outcome seen after 10 years supports this technique.
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http://dx.doi.org/10.1055/s-0037-1603769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788762PMC
February 2018

Hydatid cyst in the vastus lateralis muscle: a case report.

Clin Cases Miner Bone Metab 2017 May-Aug;14(2):262-264. Epub 2017 Oct 25.

Department of Orthopaedic and Trauma Surgery, University of Pisa, Pisa, Italy.

Hydatidosis is a zoonotic disease; human infection occurs through the consumption of food and water contaminated with the eggs of parasites of the Echinococcus type. While the liver is the most common site of infection, involvement of the musculoskeletal system is extremely rare. In the context of musculoskeletal involvement, the spine is the most commonly infected site, while the muscles are rarely infected and account for approximately <1% of cases. It has been suggested that muscles provide an unsuitable environment for the parasite, because of the presence of lactic acid. The cysts appear as slow-growing masses of soft tissue, and signs of inflammation and fistulization often coexist. We report a rare case of an hydatid cyst located in the vastus lateralis muscle of a 41-year-old man. Muscular echinococcosis is an extremely rare disease. A MRI evaluation should be taken into account as gold standard in the diagnosis. Surgical cystectomy is often indicated, and an excision with wide margins is mandatory to avoid the rupture of the cyst and anaphylaxis. Adjuvant pharmacological therapy is recommended to minimize the risk of recurrence.
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http://dx.doi.org/10.11138/ccmbm/2017.14.2.262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726224PMC
October 2017

CXCL12 Mediates Aberrant Costimulation of B Lymphocytes in Warts, Hypogammaglobulinemia, Infections, Myelokathexis Immunodeficiency.

Front Immunol 2017 4;8:1068. Epub 2017 Sep 4.

Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Rozzano, Italy.

The Warts, Hypogammaglobulinemia, Infections, Myelokathexis (WHIM) syndrome is an immunodeficiency caused by mutations in chemokine receptor CXCR4. WHIM patient adaptive immunity defects remain largely unexplained. We have previously shown that WHIM-mutant T cells form unstable immunological synapses, affecting T cell activation. Here, we show that, in WHIM patients and WHIM CXCR4 knock-in mice, B cells are more apoptosis prone. Intriguingly, WHIM-mutant B cells were also characterized by spontaneous activation. Searching for a mechanistic explanation for these observations, we uncovered a novel costimulatory effect of CXCL12, the CXCR4 ligand, on WHIM-mutant but not wild-type B cells. The WHIM CXCR4-mediated costimulation led to increased B-cell activation, possibly involving mTOR, albeit without concurrently promoting survival. A reduction in antigenic load during immunization in the mouse was able to circumvent the adaptive immunity defects. These results suggest that WHIM-mutant CXCR4 may lead to spontaneous aberrant B-cell activation, via CXCL12-mediated costimulation, impairing B-cell survival and thus possibly contributing to the WHIM syndrome defects in adaptive immunity.
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http://dx.doi.org/10.3389/fimmu.2017.01068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591327PMC
September 2017

T cell costimulation blockade blunts pressure overload-induced heart failure.

Nat Commun 2017 03 6;8:14680. Epub 2017 Mar 6.

Department of Biomedical Sciences, Humanitas University, Via Manzoni 113, Rozzano, 20089 Milan, Italy.

Heart failure (HF) is a leading cause of mortality. Inflammation is implicated in HF, yet clinical trials targeting pro-inflammatory cytokines in HF were unsuccessful, possibly due to redundant functions of individual cytokines. Searching for better cardiac inflammation targets, here we link T cells with HF development in a mouse model of pathological cardiac hypertrophy and in human HF patients. T cell costimulation blockade, through FDA-approved rheumatoid arthritis drug abatacept, leads to highly significant delay in progression and decreased severity of cardiac dysfunction in the mouse HF model. The therapeutic effect occurs via inhibition of activation and cardiac infiltration of T cells and macrophages, leading to reduced cardiomyocyte death. Abatacept treatment also induces production of anti-inflammatory cytokine interleukin-10 (IL-10). IL-10-deficient mice are refractive to treatment, while protection could be rescued by transfer of IL-10-sufficient B cells. These results suggest that T cell costimulation blockade might be therapeutically exploited to treat HF.
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http://dx.doi.org/10.1038/ncomms14680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343521PMC
March 2017

Madura foot in Europe: diagnosis of an autochthonous case by molecular approach and review of the literature.

New Microbiol 2016 Apr;39(2):156-9

Infectious and Tropical Diseases Unit, Careggi Hospital, Florence, Italy.

Madura foot is a chronic granulomatous infection of the soft-tissue of the foot and it is endemic in tropical and subtropical countries. Some cases have also been reported in local people or migrants in temperate countries. The microbiological diagnosis requires prolonged bacterial cultures in aerobic and anaerobic conditions, but the use of the molecular approach could be helpful for an early and rapid diagnosis. We describe an autochthonous case of Actinomadura madurae foot infection in an Italian woman. The diagnosis was achieved 36 months after symptoms onset by PCR detection and sequencing of 16S rDNA directly on biopsy. She started therapy with rifampin, trimethoprim-sulfamethoxazole, and amikacin. After 3 months the pain had disappeared and the swelling subsided. We reviewed the literature on Madura foot due to bacterial causative agents in Europe and observed that the median time from onset to diagnosis is high, possibly due to several factors like the difficulties of the microbiological and radiological diagnosis. Our case report and the review of literature point out that the implementation of a surveillance system, the involvement of an infectious diseases specialist, with experience in tropical diseases, and the availability of a microbiology unit to perform feasible and rapid molecular diagnostic tests could result in an earlier diagnosis and an optimal antibiotic therapy of this rare but difficult-to-treat and, above all, difficult-to-diagnose infection.
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April 2016

Tailored chemokine receptor modification improves homing of adoptive therapy T cells in a spontaneous tumor model.

Oncotarget 2016 Jul;7(28):43010-43026

Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Rozzano (Milano), Italy.

In recent years, tumor Adoptive Cell Therapy (ACT), using administration of ex vivo-enhanced T cells from the cancer patient, has become a promising therapeutic strategy. However, efficient homing of the anti-tumoral T cells to the tumor or metastatic site still remains a substantial hurdle. Yet the tumor site itself attracts both tumor-promoting and anti-tumoral immune cell populations through the secretion of chemokines. We attempted to identify these chemokines in a model of spontaneous metastasis, in order to "hijack" their function by expressing matching chemokine receptors on the cytotoxic T cells used in ACT, thus allowing us to enhance the recruitment of these therapeutic cells. Here we show that this enabled the modified T cells to preferentially home into spontaneous lymph node metastases in the TRAMP model, as well as in an inducible tumor model, E.G7-OVA. Due to the improved homing, the modified CD8+ T cells displayed an enhanced in vivo protective effect, as seen by a significant delay in E.G7-OVA tumor growth. These results offer a proof of principle for the tailored application of chemokine receptor modification as a means of improving T cell homing to the target tumor, thus enhancing ACT efficacy. Surprisingly, we also uncover that the formation of the peri-tumoral fibrotic capsule, which has been shown to impede T cell access to tumor, is partially dependent on host T cell presence. This finding, which would be impossible to observe in immunodeficient model studies, highlights possible conflicting roles that T cells may play in a therapeutic context.
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http://dx.doi.org/10.18632/oncotarget.9280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190004PMC
July 2016

Phosphatidylinositol 4-Phosphate 5-Kinase β Controls Recruitment of Lipid Rafts into the Immunological Synapse.

J Immunol 2016 Feb 15;196(4):1955-63. Epub 2016 Jan 15.

Department of Biomedical Sciences, University of Padua and Venetian Institute of Molecular Medicine, 35131 Padua, Italy.

Phosphatidylinositol 4,5-biphosphate (PIP2) is critical for T lymphocyte activation serving as a substrate for the generation of second messengers and the remodeling of actin cytoskeleton necessary for the clustering of lipid rafts, TCR, and costimulatory receptors toward the T:APC interface. Spatiotemporal analysis of PIP2 synthesis in T lymphocytes suggested that distinct isoforms of the main PIP2-generating enzyme, phosphatidylinositol 4-phosphate 5-kinase (PIP5K), play a differential role on the basis of their distinct localization. In this study, we analyze the contribution of PIP5Kβ to T cell activation and show that CD28 induces the recruitment of PIP5Kβ to the immunological synapse, where it regulates filamin A and lipid raft accumulation, as well as T cell activation, in a nonredundant manner. Finally, we found that Vav1 and the C-terminal 83 aa of PIP5Kβ are pivotal for the PIP5Kβ regulatory functions in response to CD28 stimulation.
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http://dx.doi.org/10.4049/jimmunol.1501788DOI Listing
February 2016

The CXCR4 mutations in WHIM syndrome impair the stability of the T-cell immunologic synapse.

Blood 2013 Aug 21;122(5):666-73. Epub 2013 Jun 21.

Humanitas Clinical and Research Center, Rozzano, Milan, Italy.

WHIM (warts, hypogammaglobulinemia, infections, myelokathexis) syndrome is a rare disease characterized by diverse symptoms indicative of aberrantly functioning immunity. It is caused by mutations in the chemokine receptor CXCR4, which impair its intracellular trafficking, leading to increased responsiveness to chemokine ligand and retention of neutrophils in bone marrow. Yet WHIM symptoms related to adaptive immunity, such as delayed IgG switching and impaired memory B-cell function, remain largely unexplained. We hypothesized that the WHIM-associated mutations in CXCR4 may affect the formation of immunologic synapses between T cells and antigen-presenting cells (APCs). We show that, in the presence of competing external chemokine signals, the stability of T-APC conjugates from patients with WHIM-mutant CXCR4 is disrupted as a result of impaired recruitment of the mutant receptor to the immunologic synapse. Using retrogenic mice that develop WHIM-mutant T cells, we show that WHIM-mutant CXCR4 inhibits the formation of long-lasting T-APC interactions in ex vivo lymph node slice time-lapse microscopy. These findings demonstrate that chemokine receptors can affect T-APC synapse stability and allow us to propose a novel mechanism that contributes to the adaptive immune response defects in WHIM patients.
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http://dx.doi.org/10.1182/blood-2012-10-461830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731928PMC
August 2013

Surgical treatment of central grade 1 chondrosarcoma of the appendicular skeleton.

J Orthop Traumatol 2013 Jun 6;14(2):101-7. Epub 2013 Mar 6.

Department of Orthopaedic Oncology and Reconstructive Surgery, Azienda Ospedaliera Universitaria Careggi, Florence, Italy.

Background: Diagnosis and treatment of low-grade chondrosarcoma remain controversial. We performed a review of a single-center series with the aims of assessing the oncologic outcome of these patients, verifying if intralesional curettage can be adequate treatment, and defining clinical criteria to support the surgeon and the oncologist in decision-making for surgery and subsequent follow-up.

Materials And Methods: A retrospective review of 85 patients was performed (61 females and 24 males, age range 20-76 years). The site of the lesion was the femur in 35 cases, humerus in 33, tibia in 15, and fibula in 2. Sixty-four patients were treated by intralesional curettage. Twenty-one patients with aggressive radiological patterns were treated with wide resection.

Results: Mean follow-up was 67 months (range 24-206 months). Two patients developed local recurrence, both after intralesional curettage. The difference in incidence of recurrence was not statistically significant between the two groups. No distant metastases were observed. Postsurgical complications were significantly higher in the resection group.

Conclusions: Low-grade chondrosarcoma of the appendicular skeleton without aggressive radiological patterns can be treated with intralesional surgery with good oncological outcome and very low rate of postsurgical complications. Wide resection, following surgical principles of malignant bone tumors, should be considered only when aggressive biologic behavior is evident on imaging.
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http://dx.doi.org/10.1007/s10195-013-0230-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667363PMC
June 2013

A comparison of the signalling properties of two tyramine receptors from Drosophila.

J Neurochem 2013 Apr 14;125(1):37-48. Epub 2013 Feb 14.

The Inositide Laboratory, The Babraham Institute, Cambridge, UK.

In invertebrates, the phenolamines, tyramine and octopamine, mediate many functional roles usually associated with the catecholamines, noradrenaline and adrenaline, in vertebrates. The α- and β-adrenergic classes of insect octopamine receptor are better activated by octopamine than tyramine. Similarly, the Tyramine 1 subgroup of receptors (or Octopamine/Tyramine receptors) are better activated by tyramine than octopamine. However, recently, a new Tyramine 2 subgroup of receptors was identified, which appears to be activated highly preferentially by tyramine. We examined immunocytochemically the ability of CG7431, the founding member of this subgroup from Drosophila melanogaster, to be internalized in transfected Chinese hamster ovary (CHO) cells by different agonists. It was only internalized after activation by tyramine. Conversely, the structurally related receptor, CG16766, was internalized by a number of biogenic amines, including octopamine, dopamine, noradrenaline, adrenaline, which also were able to elevate cyclic AMP levels. Studies with synthetic agonists and antagonists confirm that CG16766 has a different pharmacological profile to that of CG7431. Species orthologues of CG16766 were only found in Drosophila species, whereas orthologues of CG7431 could be identified in the genomes of a number of insect species. We propose that CG16766 represents a new group of tyramine receptors, which we have designated the Tyramine 3 receptors.
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http://dx.doi.org/10.1111/jnc.12158DOI Listing
April 2013

Primary juxtacortical myoepithelioma/mixed tumor of the bone: a report of 3 cases with clinicopathologic, immunohistochemical, ultrastructural, and molecular characterization.

Hum Pathol 2013 Apr 15;44(4):566-77. Epub 2012 Oct 15.

Division of Anatomic Pathology, Department of Critical Care Medicine and Surgery, University of Florence Medical School, 50134, Florence, Italy.

We describe the clinicopathological, immunohistochemical, and molecular features of 3 primary juxtacortical myoepithelioma/mixed tumor of bone. The patients were 2 males (13 and 23 years of age) and a 15-year-old female. The juxtacortical lesions were all located in the femur, and were surgically removed, 2 with wide margins and one with marginal margins. This latter tumor recurred locally 18 months later. The 3 patients were free of disease at 6 to 17 months follow-up. Histologically, all lesions showed a prominent multinodular architecture, and were formed by epithelioid and stellate elements, organized in solid sheets, or embedded in myxoid or chondroid matrix. Areas of osteoid formation were also observed. One tumor had the appearance of classical mixed tumor, showing aspects of duct formation and focal squamous differentiation. Immunohistochemically, all cases were positive for cytokeratins, epithelial membrane antigen, and S100 protein. The expression of other myoepithelial markers, including p63, glial fibrillary acid protein and calponin was more limited. No rearrangement of Ewing sarcoma region 1 (EWSR1) and fused in sarcoma (FUS) genes was observed by fluorescent in situ hybridization. To our knowledge, this is the first report of primary myoepitheliomas of bone arising at juxtacortical sites. These lesions must be distinguished from other benign and malignant bone and cartilage-forming surface tumors, including periosteal chondroma and chondrosarcoma, juxtacortical chondromyxoid fibroma, and periosteal and paraosteal osteosarcoma. The clinicoradiologic presentation and their histological and immunohistochemical features are distinctive enough to allow the separation from these entities.
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http://dx.doi.org/10.1016/j.humpath.2012.06.020DOI Listing
April 2013

Contrast-enhanced ultrasound: a filter role in AJCC stage I/II melanoma patients.

Oncology 2010 24;79(5-6):370-5. Epub 2011 Mar 24.

Department of Dermatology, University of Florence, Florence, Italy.

One of the most significant advances in melanoma staging is sentinel lymph node biopsy (SLNB). It is a surgical technique to detect occult nonpalpable micrometastases in regional lymph nodes. Recently, contrast-enhanced ultrasound (CEUS) was introduced as a noninvasive procedure, in spite of SLNB, for the detection of SLNs in patients with cutaneous melanoma. The main purpose of this study was to evaluate the diagnostic accuracy of CEUS in the diagnostic workup of patients with melanoma in comparison with the final histology of SLNs detected through preoperative lymphoscintigraphy. Fifteen patients with cutaneous melanoma underwent prompt excisional biopsy with narrow margins in order to avoid impairment of the melanoma lymphatic basin and were referred for SLNB according to routine indications between January and February 2009. In our study CEUS showed, albeit based on a small patient sample, a negative predictive value of 100%, that means that all negative results were confirmed by negative SLN histopathological examination; all ultrasonographically negative lymph nodes corresponded to nonmetastatic sentinel nodes.
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http://dx.doi.org/10.1159/000323494DOI Listing
June 2011

Severe osteoporosis: diagnosis of non-hip non-vertebral (NHNV) fractures.

Clin Cases Miner Bone Metab 2010 May;7(2):85-90

Department of Diagnostic Imaging - AOUC - Florence, Italy.

Osteoporotic bone, structurally altered because of reduction of bone mineral density and quality deterioration, can easily head for fracture after minimum mechanical stress.THE MOST COMMON SITES OF FRACTURE, OTHER THAN SPINE AND HIP, ARE, IN DECREASING ORDER: distal radius, forearm, proximal humerus, other femoral sites, ribs, pelvis, tibia and fibula, metatarsal bone and calcaneum. The role of diagnostic imaging is essential in detecting fractures for their immediate and correct assessment, which is necessary to the planning of treatment, whether conservative or surgical. Imaging is also important in fracture monitoring, evaluation of healing and relief of any complications.Conventional radiology is the most widely used technique in the diagnosis of fracture, although its low sensitivity, mainly in anatomically complex sites; the role of radiology is undisputed in monitoring the healing bone callus formation. Multidetector Computed Tomography (MDCT) is of great help in doubtful cases, especially in locations as "critical"; its diagnostic accuracy is very elevated with 3D and multi-planar reconstructions, allowing the surgeon to implement an appropriate therapeutic strategy. Magnetic Resonance (MR) is the most sensitive technique in the relief of minimal structural alteration of the cancellous bone, as it reveals both fracture line and surrounding bone marrow oedema. Its specificity is higher compared to MDCT and conventional radiology in the differential diagnosis between osteoporotic and malignancy pathological fracture.Bone scintigraphy is complementary to MRI in detecting occult fractures, crucial in finding metastatic disease in other locations. Ultrasound is used in limited districts, and its role is confined to the relief of cortical interruption in the fractured bone segment. In the future, technological advances with three-dimensional techniques (hr-CT, hr-MRI) may improve in vivo the diagnostic potential with an earlier detection of the ultrastructural alterations that predispose to the risk of bone fracture.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004452PMC
May 2010

A case of bilateral extensor digitorum brevis manus.

Chir Organi Mov 2008 Sep 30;92(2):133-5. Epub 2008 Aug 30.

Second Orthopaedic Clinic-University of Florence CTO, Largo Palagi 1, Florence, Italy.

We report a case of symptomatic dorsal mass in a 72-year-old man, with onset of pain during daily life efforts. On the other side, the dominant hand, a similar mass without any impairment was present. Before surgery, the mass on the left nondominant wrist was diagnosed by ultrasound as synovial ganglion: during excision, a muscular belly was found and sent to isthological evaluation, confirming the existence of an alive aberrant muscular tissue, named Extensor Digitorum Brevis Manus. Being reported in literature as occasionally bilateral, we decided to perform, 3 months later, an MRI in the contralateral asymptomatic wrist: it was possible to reveal the presence of a similar but asymptomatic mass.
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http://dx.doi.org/10.1007/s12306-008-0054-3DOI Listing
September 2008
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