Schwannomas of the peroneal nerves: Clinical and functional results of surgical treatment.

OBJECTIVES: Peroneal nerves Schwannomas are rare benign tumors. Literature is still poor of studies about clinical and functional outcomes after surgical treatment. We evaluated the pre-operative presentation of the disease and assessed clinical and functional outcomes after surgery. METHODS: We collected all the cases of peroneal nerves' neurinoma treated surgically between June 2016 and June 2020. We analyzed each patients' personal data and carried out accurate clinical examinations before and after surgery. MRI was performed both pre-operatively and post-operatively. RESULTS: We reported 9 cases of peroneal nerves schwannomas: five arising from the common peroneal nerve and four arising from the deep or superficial branches alone. Their mean size was 22.6 mm. Each patient showed sensation deficits before surgery; pre-operative MRC score was 4.2. Pre-Operative MSTS and LEFS scores were 23.6 and 64.4. Surgery was successful in each case. No local recurrence nor major complication occurred. Tumor size was significantly associated with both diagnostic delay and development of pre-operative deficits. Surgery was proven to be globally successful: post-operative evaluations highlighted a marked reduction of neurological signs and overall functional limitations. CONCLUSIONS: Surgical treatment at early stages of the disease represents a reliable and relatively safe therapeutic option.

Glass and Jamming Rheology in Soft Particles Made of PNIPAM and Polyacrylic Acid.

The phase behaviour of soft colloids has attracted great attention due to the large variety of new phenomenologies emerging from their ability to pack at very high volume fractions. Here we report rheological measurements on interpenetrated polymer network microgels composed of poly(N-isopropylacrylamide) (PNIPAM) and polyacrylic acid (PAAc) at fixed PAAc content as a function of weight concentration. We found three different rheological regimes characteristic of three different states: a Newtonian shear-thinning fluid, an attractive glass characterized by a yield stress, and a jamming state. We discuss the possible molecular mechanisms driving the formation of these states.

Implications of extraperitoneal paraaortic lymphadenectomy to the left renal vein in locally advanced cervical cancer. A Spanish multicenter study.

OBJECTIVE: Paraaortic lymph node involvement is an important prognostic factor in locally advanced cervical cancer (LACC), but the anatomic limit of aortic lymphadenectomy is controversial. We assessed the impact of extraperitoneal paraaortic lymphadenectomy up to the left renal vein in patients with LACC undergoing pretherapeutic staging. METHODS: A retrospective, multicenter study of patients with LACC stages FIGO 2009 IB2 and IIA2-IVA treated in 10 Spanish reference hospitals in gynecological oncology between 2000 and 2016. Sites of metastatic paraaortic lymph nodes above or below the inferior mesenteric artery were evaluated. Procedural-related intraoperative and early and late complications were assessed. RESULTS: We included 634 patients undergoing paraaortic lymphadenectomy, in 616 (97.2%) of which the left renal vein was the upper limit of dissection (laparoscopy 592, robotic-assisted 24). The median surgical time was 150 min (interquartile range (IQR) 120-180), blood loss was 50 mL (range 20-80), and the length of stay was 2 days (range 2-3). Metastatic paraaortic involvement was found in 114 patients (18.5%), with infrarenal metastases in 73 (64%) of them. There were 11 patients (9.6%) with infrarenal metastases only, whereas in the remaining 62 (54.4%) patients concomitant infrarenal and inframesenteric metastases were observed. Intraoperative, early, and late postoperative complications occurred in 3.6%, 7.0%, and 4.5% of patients, respectively. CONCLUSIONS: In this study of patients with LACC undergoing surgical staging, paraaortic lymphadenectomy up to the left renal vein detected skip or isolated infrarenal metastasis in 9.6% of patients, with an acceptable surgical morbidity.

Prognostic factors in patients with vulvar cancer: the VULCAN study.

OBJECTIVE: This study aimed to analyze the prognostic factors for overall and progression-free survival in patients with vulvar cancer. METHODS: This international, multicenter, retrospective study included 2453 patients diagnosed with vulvar cancer at 100 different institutions. Inclusion criteria were institutional review board approval from each collaborating center, pathologic diagnosis of invasive carcinoma of the vulva, and primary treatment performed at the participating center. Patients with intraepithelial neoplasia or primary treatment at non-participating centers were excluded. Global survival analysis and squamous cell histology subanalysis was performed. RESULTS: After excluding patients due to incomplete data entry, 1727 patients treated for vulvar cancer between January 2001 and December 2005 were registered for analysis (1535 squamous, 42 melanomas, 38 Paget's disease and 112 other histologic types). Melanomas had the worse prognosis (p=0.02). In squamous vulvar tumors, independent factors for increase in local recurrence of vulvar cancer were: no prior radiotherapy (p<0.001) or chemotherapy (p=0.006), and for distant recurrence were the number of positive inguinal nodes (p=0.025), and not having undergone lymphadenectomy (p=0.03) or radiotherapy (p<0.001), with a HR of 1.1 (95% CI 1.2 to 1.21), 2.9 (95% CI 1.4 to 6.1), and 3.1 (95% CI 1.7 to 5.7), respectively. Number of positive nodes (p=0.008), FIGO stage (p<0.001), adjuvant chemotherapy (p=0.001), tumor resection margins (p=0.045), and stromal invasion >5 mm (p=0.001) were correlated with poor overall survival, and large case volume (≥9 vs <9 cases per year) correlated with more favorable overall survival (p=0.05). CONCLUSIONS: Advanced patient age, number of positive inguinal lymph nodes, and lack of adjuvant treatment are significantly associated with a higher risk of relapse in patients with squamous cell vulvar cancer. Case volume per treating institution, FIGO stage, and stromal invasion appear to impact overall survival significantly. Future prospective trials are warranted to establish these prognostic factors for vulvar cancer.

Angioleiomyoma of the Foot: Clinical and Functional Outcomes of Surgical Treatment in a Case Series.

BACKGROUND: Angioleiomyoma is a benign soft-tissue tumor that arises from the smooth muscle cells in the tunica media of the blood vessels. Although the most common location for these neoplasms is the uterine wall, they can also originate from lower limbs. Altogether, these neoplasms account for 0.2% of all those located in the foot and ankle region. Signs and symptoms of foot angioleiomyoma can be a localized pain, swelling, and functional impairment. To date, only case reports and case series with small populations have been reported in the literature to describe the clinical picture of these neoplasms and the effectiveness of surgical treatment. In this study, we report our results of surgical treatment for angioleiomyomas of the foot. METHODS: Thirteen cases suffering from angioleiomyoma of the foot underwent surgical resection in our institution between January of 2017 and January of 2022. For each case, we recorded preoperative and postoperative symptoms, and their preoperative and postoperative functional status according to both Musculoskeletal Tumor Society Score (MSTS) and American Orthopedic Foot and Ankle Society Score (AOFAS). Eventual complications and local recurrence were reported. RESULTS: Each patient had at least mild pain before surgical treatment. The mean preoperative MSTS and AOFAS were 22.1 and 76.8, respectively. The mean tumor size was 17.7mm. Preoperatively, each patient underwent resection with wide margins. None had local recurrences or major complications at their latest follow-up. After surgery, the mean postoperative MSTS and AOFAS increased to 29.5 and 98.8, respectively. Each case had a marked increment of their functionality and a reduction of their pain after surgery. CONCLUSIONS: Our results suggest that surgical approach with tumor resection should be considered a safe and reliable treatment for foot angioleiomyomas in light of the extremely low risk of local recurrence and because of the good postoperative pain relief and functional restoration that can be obtained after the treatment.

MOREOVER: multiomics MR-guided radiotherapy optimization in locally advanced rectal cancer.

BACKGROUND: Complete response prediction in locally advanced rectal cancer (LARC) patients is generally focused on the radiomics analysis of staging MRI. Until now, omics information extracted from gut microbiota and circulating tumor DNA (ctDNA) have not been integrated in composite biomarkers-based models, thereby omitting valuable information from the decision-making process. In this study, we aim to integrate radiomics with gut microbiota and ctDNA-based genomics tracking during neoadjuvant chemoradiotherapy (nCRT). METHODS: The main hypothesis of the MOREOVER study is that the incorporation of composite biomarkers with radiomics-based models used in the THUNDER-2 trial will improve the pathological complete response (pCR) predictive power of such models, paving the way for more accurate and comprehensive personalized treatment approaches. This is due to the inclusion of actionable omics variables that may disclose previously unknown correlations with radiomics. Aims of this study are: - to generate longitudinal microbiome data linked to disease resistance to nCRT and postulate future therapeutic strategies in terms of both type of treatment and timing, such as fecal microbiota transplant in non-responding patients. - to describe the genomics pattern and ctDNA data evolution throughout the nCRT treatment in order to support the prediction outcome and identify new risk-category stratification agents. - to mine and combine collected data through integrated multi-omics approaches (radiomics, metagenomics, metabolomics, metatranscriptomics, human genomics, ctDNA) in order to increase the performance of the radiomics-based response predictive model for LARC patients undergoing nCRT on MR-Linac. EXPERIMENTAL DESIGN: The objective of the MOREOVER project is to enrich the phase II THUNDER-2 trial (NCT04815694) with gut microbiota and ctDNA omics information, by exploring the possibility to enhance predictive performance of the developed model. Longitudinal ctDNA genomics, microbiome and genomics data will be analyzed on 7 timepoints: prior to nCRT, during nCRT on a weekly basis and prior to surgery. Specific modelling will be performed for data harvested, according to the TRIPOD statements. DISCUSSION: We expect to find differences in fecal microbiome, ctDNA and radiomics profiles between the two groups of patients (pCR and not pCR). In addition, we expect to find a variability in the stability of the considered omics features over time. The identified profiles will be inserted into dedicated modelling solutions to set up a multiomics decision support system able to achieve personalized treatments.

Influence of a Solid Surface on PNIPAM Microgel Films.

Stimuli-responsive microgels have attracted great interest in recent years as building blocks for fabricating smart surfaces with many technological applications. In particular, PNIPAM microgels are promising candidates for creating thermo-responsive scaffolds to control cell growth and detachment via temperature stimuli. In this framework, understanding the influence of the solid substrate is critical for tailoring microgel coatings to specific applications. The surface modification of the substrate is a winning strategy used to manage microgel-substrate interactions. To control the spreading of microgel particles on a solid surface, glass substrates are coated with a PEI or an APTES layer to improve surface hydrophobicity and add positive charges on the interface. A systematic investigation of PNIPAM microgels spin-coated through a double-step deposition protocol on pristine glass and on functionalised glasses was performed by combining wettability measurements and Atomic Force Microscopy. The greater flattening of microgel particles on less hydrophilic substrates can be explained as a consequence of the reduced shielding of the water-substrate interactions that favors electrostatic interactions between microgels and the substrate. This approach allows the yielding of effective control on microgel coatings that will help to unlock new possibilities for their application in biomedical devices, sensors, or responsive surfaces.

Impact of body composition parameters on radiation therapy compliance in locally advanced rectal cancer: A retrospective observational analysis.

Background: The impact of body composition and sarcopenia in locally advanced rectal cancer (LARC) is still unclear, even several studies have been published on this issue. Our study aims to analyze the impact of sarcopenia on neoadjuvant chemoradiotherapy (nCRT) tolerance and survival outcomes. Methods: This is a retrospective, monocentric study where LARC patients treated between 2010 and 2020 were enrolled. A single slice, from the pre-therapy simulation computed tomography (CT) scan, was used to perform the body composition analysis with dedicated software. The primary endpoint was the impact of body composition on radiotherapy (RT) interruption secondarily on overall survival (OS), disease-free survival (DFS), and local control (LC). Results: The study included 628 LARC patients (40.9 % female, mean age 63.4 years): 24 % had low skeletal muscle index (SMI), 30 % had low muscle density (MD) and 17 (10.3 % of obese) were sarcopenic obese. Higher BMI (OR 2.38, 95 % CI 1.36-4.01) and lower SMI (0.73, 95 % CI 0.55-0.94) resulted as independent predictors of RT interruption. Sarcopenic obesity (HR 2.83, 95 % CI 1.24-6.45) was related to worse OS, while MD (0.96, 95 % CI 0.93-0.98), and higher SMI (0.97, 95 % CI 0.95-0.99) were related to better OS; a lower MD remained also associated even in adjusted multivariable analysis (0.96, 95 % CI0.93-0.98). Moreover, higher visceral adipose tissue (VAT) resulted associated with worse DFS (1.02, 95 % CI 1.01-1.03), while higher SMI was related to better Local Control (0.96, 95 % CI 0.93-0.99). Conclusions: Body composition analysis, particularly of muscle and fat masses, may be a useful tool for better management of LARC patients undergoing RT. Increased collaboration between radiation oncologists and clinical nutritionists is advisable, to enable early nutritional support of LARC.

Outcomes of Long Bones Treated With Carbon-Fiber Nails for Oncologic Indications: International Multi-institutional Study.

BACKGROUND: Intramedullary nail fixation is commonly used for prophylactic stabilization of impending and fixation of complete pathological fractures of the long bones. However, metallic artifacts complicate imaging evaluation for bone healing or tumor progression and postoperative radiation planning. Carbon-fiber implants have gained popularity as an alternative, given their radiolucency and superior axial bending. This study evaluates incidences of mechanical and nonmechanical complications. METHODS: Adult patients (age 18 years and older) treated with carbon-fiber nails for impending/complete pathological long bone fractures secondary to metastases from 2013 to 2020 were analyzed for incidences and risk factors of mechanical and nonmechanical complications. Mechanical complications included aseptic screw loosening and structural failures of host bone and carbon-fiber implants. Deep infection and tumor progression were considered nonmechanical. Other complications/adverse events were also reported. RESULTS: A total of 239 patients were included; 47% were male, and 53% were female, with a median age of 68 (IQR, 59 to 75) years. Most common secondary metastases were related to breast cancer (19%), lung cancer (19%), multiple myeloma (18%), and sarcoma (13%). In total, 17 of 30 patients with metastatic sarcoma received palliative intramedullary nail fixation for impending/complete pathological fractures, and 13 of 30 received prophylactic nail stabilization of bone radiated preoperatively to manage juxta-osseous soft-tissue sarcomas, where partial resection of the periosteum or bone was necessary for negative margin resection. 33 (14%) patients had complications. Mechanical failures included 4 (1.7%) structural host bone failures, 7 (2.9%) implant structural failures, and 1 (0.4%) aseptic loosening of distal locking screws. Nonmechanical failures included 8 (3.3%) peri-implant infections and 15 (6.3%) tumor progressions with implant contamination. The 90-day and 1-year mortalities were 28% (61/239) and 53% (53/102), respectively. The literature reported comparable failure and mortality rates with conventional titanium treatment. CONCLUSIONS: Carbon-fiber implants might be an alternative for treating impending and sustained pathological fractures secondary to metastatic bone disease. The seemingly comparable complication profile warrants further cohort studies comparing carbon-fiber and titanium nail complications.

Conversion in a Resectable Tumor after Denosumab Neoadjuvant in a Large Dorsal Giant Cells Tumor: A Case Report and a Literature Review.

Giant cell tumors of bone are a rare entity, usually occurring in young patients and characteristically arising in the long bones. The spinal location is rare and usually presents with pain and/or neurological symptoms. The treatment of choice is surgery. Treatment with Denosumab, a bisphosphonate inhibitor of RANK-L, which is highly expressed in these tumors, has shown extensive activity in unresectable patients or those undergoing incomplete surgery. Preoperative treatment with this drug is gaining increasing interest, as its high potency in tumor reduction in this subtype of neoplasm has allowed resectability in selected patients. We present the case of a young patient with a large spinal tumor who, after neoadjuvant Denosumab, underwent complete en bloc surgery with clean margins and a great pathological response.

Aneurysmal Bone Cyst of the Pelvis in Children and Adolescents: Effectiveness of Surgical Treatment with Curettage, Cryotherapy and Bone Grafting.

BACKGROUND: Aneurysmal bone cysts (ABCs) are benign but locally aggressive cystic lesions of the bone. Pelvic ABCs are extremely rare and hard to treat due to their high risk of local recurrence and the tough access to pelvic bones. METHODS: In this retrospective study, we evaluated pediatric cases with pelvic ABC treated with curettage, cryotherapy and bone grafting treated in our institution between 2016 and 2022. Complications were recorded, as well as local recurrences. Patients' post-operative functionality was assessed with the MSTS score. RESULTS: Fourteen consecutive cases were included in our study. Their mean age at surgery was 13.5 years. The mean lesion size was 55 mm. The mean follow-up was 38 months. Two cases (11.8%) had local recurrences, which were successfully treated with further curettage. At their latest FU, 13 cases were continuously disease free (CDF), and one had no evidence of disease (NED). Only one case had a post-operative compilation (wound dehiscence). Patients' mean post-operative MSTS score was 29.6. CONCLUSIONS: Pelvic ABCs are a challenge, even for the most experienced orthopedic surgeon. Our study suggests that the association of an accurate curettage, intraoperative cryotherapy and bone grafting can be a reliable and effective therapeutic option for large-sized ABCs of the pelvis.

Femoral neck fractures treated with cannulated screws: can surgeons predict functional outcomes and minimize the risk of necrosis?

BACKGROUND AND AIM: Femoral neck fractures are among the most frequent in mankind. Screw fixation is considered a suitable approach specially for undisplaced or slightly displaced fractures that occur to young patients. We conducted our study in order to evaluate both functional outcomes and complication rates of patients who received this treatment in our institution. A particular focus was given to the aseptic necrosis of the head, trying to identify if anamnestic, clinical or radiological data could play a significant role as prognostic factors. METHODS: For each case who was treated with screw fixation due to a femoral neck fracture, we recorded data regarding, among the others, BMI and whether they used tobacco products or corticosteroids on a regular basis. Necrosis of the femoral head and mechanical complications were recorded. Functional outcome was evaluated using the Harris Hip Score.      Results: 74 cases were included in our study. The mean Harris Hip score was 89.5. Aseptic necrosis of the femoral head occurred in 9 cases (12.2%). Regular use of tobacco was associated with a higher risk to develop necrosis (p=0.007). The Body Mass Index was significantly higher in cases who had necrosis compared to the rest of our population (p=0.043) and was inversely proportional to the post-operative Harris hip score (p=0.001). CONCLUSIONS: While considering screw fixation to treat cases with femoral neck fractures, patient's weight and use of tobacco should be considered as prognostic factors.  (www.actabiomedica.it).

Is the Combination of Platelet-Rich Plasma and Hyaluronic Acid the Best Injective Treatment for Grade II-III Knee Osteoarthritis? A Prospective Study.

Background: Knee osteoarthritis is a common disease with increasing incidence and prevalence in western countries. It can cause severe pain and functional limitations, thereby representing a threat for patients' quality of life and a burden for national health systems. Intra-articular injections with hyaluronic acid (HA) and platelet-rich plasma (PRP) have been used for decades in order to reduce the symptoms caused by osteoarthritis. In recent years, a combination of HA and PRP has been introduced in clinical practice with the aim to minimize the clinical presentation of osteoarthritis and potentially delay articular degeneration. Materials and Methods: Sixty cases with grade II-III knee osteoarthritis according to the Kellgren-Lawrence classification were included in a prospective study, focused on the evaluation of clinical and functional outcomes after intra-articular knee injections. Cases were randomly divided into three groups. Twenty cases (Group A) were injected with HA, 20 (Group B) had PRP, and the remaining 20 (Group C) received a combination of HA and PRP. Basal WOMAC score and VAS score were recorded before the treatment and repeated within 3 and 6 months after the treatment. Results: At 6-month follow-up, Group C (PRP + HA) was the one with the lowest WOMAC and VAS mean values. It was also the only group that reported a reduction in the two values both in the first three months and in the following three months. No major complication was recorded. Conclusion: The combination of platelet-rich plasma and hyaluronic acid can be effective in the treatment of grade II-III knee osteoarthritis in a short-to-mid-term scenario. It represents an innovative and valuable alternative to the administration of its two components alone.

Outcomes of Surgical Treatment for Localized Tenosynovial Giant-Cell Tumor of the Foot and Ankle: A Case Series.

Background: Giant cell tumor of the tendon sheath (GCTTS), also termed Tenosynovial giant cell tumor (TGCT), is a locally aggressive tumor which originates from tendon sheaths or bursas. Around 3-5% of these tumors arise from foot and ankle. Localized lesions in this area are often manifested as firm masses or nodules with slow but continuous progression through months and years. Pain associated with weight-bearing, as well as limitations in joint motions, may be reported, depending on tumor's location. Surgery is the treatment of choice for the definitive removal of GCTTSs with the aim to eradicate the neoplasm and restore the lower limb's functionality. Methods: Thirteen cases suffering from GCTTS of the foot and ankle underwent surgical resection at our institution between 2017 and 2022. For each case we recorded pre-operative and post-operative symptoms, as well as their pre-operative and post-operative functional status according to both MSTS and AOFAS scores. Eventual complications and local recurrences were reported. Results: Each patient experienced an at least mild pain before surgical treatment. The mean pre-operative MSTS and AOFAS scores were 22.8 and 70.7, respectively. The mean tumor size was 17.7 mm. Each patient received a resection with wide margins. Two cases (15.4%) had local recurrences. None had major complications at their latest follow-up. After the surgery, the mean post-operative MSTS and AOFAS scores increased to 28.3 and 92.2, respectively. Conclusion: Resection with wide margins for foot and ankle GCTTS is effective in restoring the patients' lower limb functionality and is associated with reasonable local recurrence rates.

KIT 1 (Keep in Touch) Project-Televisits for Cancer Patients during Italian Lockdown for COVID-19 Pandemic: The Real-World Experience of Establishing a Telemedicine System.

To evaluate the adoption of an integrated eHealth platform for televisit/monitoring/consultation during the COVID-19 pandemic. METHODS: During the lockdown imposed by the Italian government during the COVID19 pandemic spread, a dedicated multi-professional working group was set up in the Radiation Oncology Department with the primary aim of reducing patients' exposure to COVID-19 by adopting de-centralized/remote consultation methodologies. Each patient's clinical history was screened before the visit to assess if a traditional clinical visit would be recommended or if a remote evaluation was to be preferred. Real world data (RWD) in the form of patient-reported outcomes (PROMs) and patient reported experiences (PREMs) were collected from patients who underwent televisit/teleconsultation through the eHealth platform. RESULTS: During the lockdown period (from 8 March to 4 May 2020) a total of 1956 visits were managed. A total of 983 (50.26%) of these visits were performed via email (to apply for and to upload of documents) and phone call management; 31 visits (1.58%) were performed using the eHealth system. Substantially, all patients found the eHealth platform useful and user-friendly, consistently indicating that this type of service would also be useful after the pandemic. CONCLUSIONS: The rapid implementation of an eHealth system was feasible and well-accepted by the patients during the pandemic. However, we believe that further evidence is to be generated to further support large-scale adoption.

Molecular origin of the two-step mechanism of gellan aggregation.

Among hydrocolloids, gellan is one of the most studied polysaccharides due to its ability to form mechanically stable gels. Despite its long-standing use, the gellan aggregation mechanism is still not understood because of the lack of atomistic information. Here, we fill this gap by developing a new gellan force field. Our simulations offer the first microscopic overview of gellan aggregation, detecting the coil to single-helix transition at dilute conditions and the formation of higher-order aggregates at high concentration through a two-step process: first, the formation of double helices and then their assembly into superstructures. For both steps, we also assess the role of monovalent and divalent cations, complementing simulations with rheology and atomic force microscopy experiments and highlighting the leading role of divalent cations. These results pave the way for future use of gellan-based systems in a variety of applications, from food science to art restoration.

Peripheral schwannomas of the tibial nerve: surgical results in a case series.

BACKGROUND AND AIM OF THE WORK: Schwannomas of the lower limb are uncommon benign tumors and those arising from Tibial Nerve are particularly rare. We report our experience on the topic, with particular attention to clinical presentation and lower limbs overall functionality before and after treatment. Our aim is to assess clinical impairment caused by the tumor and evaluate the effectiveness of surgical treatment. MATERIALS AND METHODS: Time between symptoms outbreak and diagnosis, as well as pre- operative tumor size were evaluated for each case. Pre-operative and post-operative overall lower limb functionality were assessed using both MSTS and LEFS scores. Sensitive symptoms and muscular strength were also evaluated before and after surgery. RESULTS: 7 patients were included in our study. The mean follow-up was 22.9 months. Average diagnostic delay was 8 months and tumor size was 29.3mm. Before surgery each patient had positive Hoffmann-Tinel sign and an at least mild paresthesia, 57% of our cases had slight reduction of muscular strength. Pre-operative MSTS score was 24.4 and LEFS score was 64.7. Tumor size and diagnostic delay were associated with pre-operative functionality. No major local complication was recorded during or after surgery. Each patient with pre-operative sensitive or motorial deficit benefited the effects of surgical treatment. CONCLUSIONS: Our cases suggest early diagnosis could reduce the impact of the disease on patients' activities of daily living and quality of life. Surgery, for its part, represents a safe and reliable approach to Tibial Nerve schwannomas with good chances of clinical and functional remission.

Understanding the metal free alginate gelation process.

Alginate is a natural polysaccharide that has been recently gaining increasing attention as a biomaterial in the field of tissue engineering due to its favourable biocompatibility and gelation properties. Alginate hydrogels are commonly made by ionic crosslinking in the presence of divalent cations. Only a few studies have attempted to prepare alginate hydrogels without the presence of metal cations. Here the formation of metal free alginate hydrogels in the presence of the amino-acid glutamine is investigated. The transition from sol to gel is monitored by rheological measurements in the viscoelastic regime that reveal how the charged or neutral form of glutamine induces deep differences in the gelling ability. In particular, we show that the storage, G', and loss, G'', moduli differ significantly by shifting the glutamine zwitterionic equilibrium. Protonated amino acid could induce a shielding effect of the electrostatic repulsion of the alginate chains. Stable gels are obtained in the presence of a larger amount of free organic acid that gives rise to chain crosslink junctions and chain-chain stabilization. This opens up the possibility of preparing metal-free alginate hydrogels based on amino acid equilibria being pH sensitive.

Thermal Behaviour of Microgels Composed of Interpenetrating Polymer Networks of Poly(N-isopropylacrylamide) and Poly(acrylic acid): A Calorimetric Study.

Stimuli-responsive microgels have recently attracted great attention in fundamental research as their soft particles can be deformed and compressed at high packing fractions resulting in singular phase behaviours. Moreover, they are also well suited for a wide variety of applications such as drug delivery, tissue engineering, organ-on-chip devices, microlenses fabrication and cultural heritage. Here, thermoresponsive and pH-sensitive cross-linked microgels, composed of interpenetrating polymer networks of poly(N-isopropylacrylamide) (PNIPAM) and poly(acrylic acid) (PAAc), are synthesized by a precipitation polymerization method in water and investigated through differential scanning calorimetry in a temperature range across the volume phase transition temperature of PNIPAM microgels. The phase behaviour is studied as a function of heating/cooling rate, concentration, pH and PAAc content. At low concentrations and PAAc contents, the network interpenetration does not affect the transition temperature typical of PNIPAM microgel in agreement with previous studies; on the contrary, we show that it induces a marked decrease at higher concentrations. DSC analysis also reveals an increase of the overall calorimetric enthalpy with increasing concentration and a decrease with increasing PAAc content. These findings are discussed and explained as related to emerging aggregation processes that can be finely controlled by properly changing concentration, PAAc content an pH. A deep analysis of the thermodynamic parameters allows to draw a temperature-concentration state diagram in the investigated concentration range.

Chemical-Physical Behaviour of Microgels Made of Interpenetrating Polymer Networks of PNIPAM and Poly(acrylic Acid).

Microgels composed of stimuli responsive polymers have attracted worthwhile interest as model colloids for theorethical and experimental studies and for nanotechnological applications. A deep knowledge of their behaviour is fundamental for the design of new materials. Here we report the current understanding of a dual responsive microgel composed of poly(N-isopropylacrylamide) (PNIPAM), a temperature sensitive polymer, and poly(acrylic acid) (PAAc), a pH sensitive polymer, at different temperatures, PAAc contents, concentrations, solvents and pH. The combination of multiple techniques as Dynamic Light Scattering (DLS), Raman spectroscopy, Small Angle Neutron Scattering (SANS), rheology and electrophoretic measurements allow to investigate the hydrodynamic radius behaviour across the typical Volume Phase Transition (VPT), the involved molecular mechanism and the internal particle structure together with the viscoelastic properties and the role of ionic charge in the aggregation phenomena.