Diagnostic accuracy of a velcro sound detector (VECTOR) for interstitial lung disease in rheumatoid arthritis patients: the InSPIRAtE validation study (INterStitial pneumonia in rheumatoid ArThritis with an electronic device).

BACKGROUND: Interstitial lung disease (ILD) is a severe systemic manifestation of rheumatoid arthritis (RA). High-resolution computed tomography (HRCT) represents the gold standard for the diagnosis of ILD, but its routine use for screening programs is not advisable because of both high cost and X-ray exposure. Velcro crackles at lung auscultation occur very early in the course of interstitial pneumonia, and their detection is an indication for HRCT. Recently, we developed an algorithm (VECTOR) to detect the presence of Velcro crackles in pulmonary sounds and showed good results in a small sample of RA patients. The aim of the present investigation was to validate the diagnostic accuracy of VECTOR in a larger population of RA patients, compared with that of the reference standard of HRCT, from a multicentre study. METHODS: To avoid X-ray exposure, we enrolled 137 consecutive RA patients who had recently undergone HRCT. Lung sounds of all patients were recorded in 4 pulmonary fields bilaterally with a commercial electronic stethoscope (ES); subsequently, all HRCT images were blindly evaluated by a radiologist, and audio data were analysed by means of VECTOR. RESULTS: Fifty-nine of 137 patients showed ILD (43.1%). VECTOR correctly classified 115/137 patients, showing a diagnostic accuracy of 83.9% and a sensitivity and specificity of 93.2 and 76.9%, respectively. CONCLUSIONS: VECTOR may represent the first validated tool for the screening of RA patients who are suspected for ILD and who should be directed to HRCT for the diagnosis. Moreover, early identification of RA-ILD could contribute to the design of prospective studies aimed at elucidating unclear aspects of the disease.

Accreditation for colorectal cancer surgery in Italy. Preliminary results of a new program in a district hospital.

Accreditation for colorectal (CR) cancer surgery has become a major issue in Italy. This study aimed to analyze the early results of a newly structured program for the treatment of CR cancer in a rural district hospital. Between 2017 and 2018, a total of 214 consecutive patients underwent a CR procedure for malignancy. There were 113 men and 101 women of a mean age of 74 years. Primary CR adenocarcinoma was diagnosed in 210 patients (98%). The incidence of stage I, II, III, and IV disease was 26%, 31%, 24%, and 19% respectively. Hospital volume increased tenfold compared to previous years. Anatomical resection was performed in 204 patients. Right-sided resection and resection of the transverse colon or left angle were performed in 76 (37%) and 14 (7%) patients, respectively. A restorative left sided CR resection was performed in 80 patients (39%), whereas Hartmann procedure and Miles abdominal-perineal resection were performed in 27 (13%) and 6 (3%) patients, respectively. Total colectomy with ileorectal anastomosis was performed in one patient, and two more patients underwent atypical resection. Emergency cecostomy was performed in 15 patients and a colic endoprosthesis was implanted in one patient for obstruction and seven underwent resection afterwards. Laparoscopic resection was performed in 118 patients (57.8%), and the conversion rate was 2%. Overall morbidity, reintervention, and mortality rates were 24.6%, 3,7%, and 3.2%, respectively. The incidence of AL was 4.6%, and two patients died of the consequences of it after right hemicolectomy. Five more elderly patients died for non-surgical related medical complications. The median hospital stay was ten days, and early unplanned readmission rate was 2%. Hospital and surgeon requirements, in terms of minimum volume, organization, and surgical outcome were fulfilled. A rural district hospital can become a tertiary referral center for the surrounding districts without imposing unreasonable travel burdens for patients. CR surgery represents a capital investment for the hospital administration since it shows the effectiveness and quality of care.

A novel dressing for the combined delivery of platelet lysate and vancomycin hydrochloride to chronic skin ulcers: Hyaluronic acid particles in alginate matrices.

The aim of the present work was to develop a medication allowing for the combined delivery of platelet lysate (PL) and an anti-infective model drug, vancomycin hydrochloride (VCM), to chronic skin ulcers. A simple method was set up for the preparation of hyaluronic acid (HA) core-shell particles, loaded with PL and coated with calcium alginate, embedded in a VCM containing alginate matrix. Two different CaCl2 concentrations were investigated to allow for HA/PL core-shell particle formation. The resulting dressings were characterized for mechanical and hydration properties and tested in vitro (on fibroblasts) and ex-vivo (on skin biopsies) for biological activity. They were found of sufficient mechanical strength to withstand packaging and handling stress and able to absorb a high amount of wound exudate and to form a protective gel on the lesion area. The CaCl2 concentration used for shell formation did not affect VCM release from the alginate matrix, but strongly modified the release of PGFAB (chosen as representative of growth factors present in PL) from HA particles. In vitro and ex vivo tests provided sufficient proof of concept of the ability of dressings to improve skin ulcers healing.

Alpha tocopherol loaded chitosan oleate nanoemulsions for wound healing. Evaluation on cell lines and ex vivo human biopsies, and stabilization in spray dried Trojan microparticles.

An amphiphilic chitosan salt, chitosan oleate (CS-OA), was previously proposed for the physical stabilization of lemongrass antimicrobial nanoemulsions (NE) through a mild spontaneous emulsification process. As both chitosan and oleic acid are described in the literature for their positive effects in wound healing, in the present study CS-OA has been proposed to encapsulate alpha tocopherol (αTph) in NEs aimed to skin wounds. A NE formulation was developed showing about 220 nm dimensions, 36% drug loading, and αTph concentration up to 1 mg/ml. Both CS-OA and αTph NE stimulated cell proliferation on keratinocytes and fibroblast cell cultures, and in ex vivo skin biopsies, suggesting the suitability of CS-OA and of the antioxidant agent for topical application in wound healing. αTph stability was further improved with respect of encapsulation, by spray drying the NE into a powder (up to about 90% αTph residual after 3 months). The spray drying process was optimized, to improve powder yield and αTph recovery, by a design of experiments approach. The powder obtained was easily re-suspended to deliver the NE and resulted able to completely release αTph.

Carvacrol/clay hybrids loaded into in situ gelling films.

The aim of the present work was the development of polymer films loaded with a carvacrol (CVR)/clay hybrid (HYBD) for the delivery of CRV in infected skin ulcer treatment. Different clays were considered: montmorrilonite, halloysite and palygorskite (PHC). CRV incorporation in PHC reduced its volatility. HYBD showed 20% w/w CRV loading capacity and was able to preserve CRV antioxidant properties. HYBD was characterized by improved antimicrobial properties against S. aureus and E. coli and cytocompatibility towards human fibroblasts with respect to pure CRV. Films were prepared by casting an aqueous dispersion containing poly(vinylalcohol) (PVA), poly(vinylpyrrolidone) (PVP), chitosan glutamate (CS), sericin and HYBD. Optimization of film composition was supported by a Design of Experiments (DoE) approach. In a screening phase, a full factorial design (FFD) was used and the following factors were investigated at two levels: PVA (12-14%w/w), PVP (2-4%w/w) and CS (0.134-0.5%w/w) concentrations. For the optimization phase, FFD was expanded to a "central composite design". The response variables considered were: elongation, tensile strength and buffer absorption of films, durability of the gels formed after film hydration. Upon hydration, the optimized film formed a viscoelastic gel able to protect the lesion area and to modulate CRV release.

The role of minimally invasive surgery in the treatment of cholangiocarcinoma.

Cholangiocarcinoma (CC) is the second most common type of primary liver cancer after hepatocellular carcinoma. Surgical resection is considered the only curative treatment for CC. In general, laparoscopic liver surgery (LLS) is associated with improved short-term outcomes without compromising the long-term oncological outcome. However, the role of LLS in the treatment of CC is not yet well established. In addition, CC may arise in any tract of the biliary tree, thus requiring different types of treatment, including pancreatectomies and extrahepatic bile duct resections. This review presents and discusses the state of the art in the laparoscopic and robotic surgical treatment of all types of CC. An electronic search was performed to identify all studies dealing with laparoscopic or robotic surgery and cholangiocarcinoma. Laparoscopic resection in patients with intrahepatic CC (ICC) is feasible and safe. Regarding oncologic adequacy, as R0 resections, depth of margins, and long-term overall and disease-free survival, laparoscopy is comparable to open procedures for ICC. An adequate patient selection is required to obtain optimal results. Use of laparoscopy in perihilar CC (PHC) has not gained popularity. Further studies are still needed to confirm the benefit of this approach over conventional surgery for PHC. Laparoscopic pancreaticoduodenectomy for distal CC (DCC) represents one of the most advanced abdominal operations owing to the necessity of a complex dissection and reconstruction and has also had small widespread so far. Minimally invasive surgery seems feasible and safe especially for ICC. Laparoscopy for PHC is technically challenging notably for the caudate lobectomy. Not least as for the LLR, the robotic approach for DCC appears technically achievable in selected patients.

Palmitoyl Glycol Chitosan Micelles for Corneal Delivery of Cyclosporine.

Different substitution degrees of palmitoyl glycol chitosan (PGC), prepared according to the literature, were used to obtain polymeric micelles that have been assessed in comparison with Pluronic F127 micelles as possible carriers for poorly soluble drugs, such as cyclosporine A. Both PGC and Pluronic micelles were studied for their interactions with cell culture substrates. The least substituted and most hydrophilic derivative, PGC21 (approximately 5% substitution), showed a strong association with cyclosporine, more than tripling the colloidal concentration with respect to the saturated solution. It showed a greater ability to open Caco-2 tight junctions and to enhance the permeability of Caco-2 substrates with respect to micelles based on higher palmitoyl substitution, conceivably due to the lower modification of the chitosan chains. Permeation and penetration experiments were performed with PGC21 and Pluronic micelles on a rabbit corneal epithelial cell line (RCE) and on excised pig corneas. It was found that both PGC and Pluronic micelles could increase the permeation of the fluorescent probe rhodamine B through RCE cells by more than ten-fold. In RCE and in pig cornea, the micelles improved the penetration of both rhodamine and cyclosporine. For cyclosporine, the PGC21 micelles allowed penetration of approximately 1 µg/mg cyclosporine A in corneal tissue, demonstrating a potential for use in immunosuppression therapies.

Leiomyosarcoma of the inferior vena cava.

BACKGROUND: Leiomyosarcoma (LMS) of the inferior vena cava (IVC) is a rare tumor with poor prognosis. Optimal treatment includes complete resection of the malignant lesion. METHODS: From 1997 to 2013, eight patients underwent surgery in our department for IVC LMS. LMS was considered to arise from the IVC if the tumor presented intraluminal development or if complete resection (R0) required removal of part of the IVC with an extraluminal mass. RESULTS: There were two grade 1 tumors (25%), four grade 2 (50%) and two grade 3 (25%). The median length of stay was 16 days and there were no peri-operative deaths. Median of follow-up was 56 months and mean overall survival was 120 months. Mean 3-year survival rate was 87.5%. Six patients (75%) developed a local recurrence. Four patients died from disease progression. Two patients underwent to surgery for recurrence. CONCLUSION: IVC LMS have a poor prognosis if surgical resection cannot be achieved. Long-term survival is related to an extensive surgery, in the event of recurrence, surgery should again be proposed and may be effective for controlling disease progression, possibly improving survival.

Effect of different chilling rates on the quality parameters of mule duck fatty liver.

The aim of this experiment was to study the effect of chilling rates on the quality features of fatty livers. Three different chilling rates were applied: ultra-fast (UF), fast (FA), and slow (SL). Technological and proteomic results were compared at time T1 when the internal temperature of livers reached 10°C and at time T2=24 h post mortem. Samples from the UF group reached the T1 temperature at 50 min post mortem and had the least hard livers and the lowest cooking loss percentage (25±9%) at time T2=24 h post mortem (P-value of <0.01). The FA and SL groups reached the T1 temperature after 120 and 210 min post mortem and presented higher melting (36±9 and 41±9%, respectively, at time T2) and harder livers compared to the UF group. In parallel, we conducted semi-quantifications of proteins by electrophoresis and proteolytic activities by mono-dimensional zymography for three families of proteases: Matrix metalloproteases (MMP), Cathepsins, and Calpains. The proteomic assays revealed less modified proteolytic activities in samples from the UF group, and less associated proteins degradations than in samples from the FA and the SL groups. Effects of the different chilling rates were mainly significant at time T2 (24 h post mortem). As a conclusion we were able to highlight an indirect positive relation between proteolysis and melting yield in ducks' fatty liver.

Hepatoblastoma in a 14 month-old female.

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Complete surgical resection is the best treatment choice with a good prognosis in most cases. We present the case of a 14 month-old female patient was admitted to the pediatric surgery unit due to an abdominal mass localized in the right upper quadrant. The diagnosis retained was hepatoblastoma, so the patient underwent preoperative chemotherapy. The final size of the tumor permitted a complete surgical resection through a right subcostal incision enlarged to the left. Hepatoblastoma is the most common malignant liver tumor in children, more frequent in male than in female and typically presenting before 3 years of age as an abdominal mass found accidentally. Recent treatment strategies, consisting of chemotherapy combined with extensive surgery and in extreme cases liver transplantation, have improved the prognosis during the last years although HB's etiology and management are still subjects of debate.

Intra-arterial yttrium-90 radioembolization combined with systemic chemotherapy is a promising method for downstaging unresectable huge intrahepatic cholangiocarcinoma to surgical treatment.

PURPOSE: To evaluate the downstaging efficacy of yttrium-90 radioembolization (Ytt-90)-associated with chemotherapy and the results of surgery for initially unresectable huge intrahepatic cholangiocarcinoma (ICC). METHODS: Between January 2008 and October 2013, unresectable ICC were treated with chemotherapy and Ytt-90. Patients with unique tumors localized to noncirrhotic livers and without extrahepatic metastasis were considered to be potentially resectable and were evaluated every 2 months for possible secondary resection. RESULTS: Forty-five patients were treated for unresectable ICCs; ten had potentially resectable tumors, and eight underwent surgery. Initial unresectability was due to the involvement of the hepatic veins or portal vein of the future liver remnant in seven and one cases, respectively. Preoperative treatment induced significant decreases in tumor volume (295 vs. 168 ml, p = 0.02) and allowed for R0 resection in all cases. Three patients (37.5 %) had Clavien-Dindo grade three or higher complications, including two postoperative deaths. The median follow-ups were 15.6 [range 4-40.7] months after medical treatment initiation and 7.2 [0.13-36.4] months after surgery. At the end of the study period, five patients were still alive, with one patient still alive 40 months after medical treatment initiation (36.4 months after surgery); two patients experienced recurrences. CONCLUSIONS: For initially unresectable huge ICCs, chemotherapy with Ytt-90 radioembolization is an effective downstaging method that allows for secondary resectability.

Opportunities offered by chitosan-based nanotechnology in mucosal/skin drug delivery.

Chitosan (CS) based nanocarriers have been extensively studied starting from early 90s. The unique properties of CS and in particular its capability to interact with various epithelia and its mucoadhesion potential have attracted many researchers. The mild preparation conditions of CS nanosystems offer the opportunities to load stress sensitive hydrophilic macromolecules such as proteins and genetic materials. Moreover CS nanosystems are able to protect their cargo from the environment (pH, enzymes). The safety issues related to this polymer seem in part overcome at least for CS as polymeric solution. For this reason skin and mucosae, in particular buccal and vaginal ones, seem the more promising administration routes with lower technical and regulatory challenges. Even if several papers focused on CS nanocarriers for skin and mucosal (buccal and vaginal) administration have been published, other work should be done aiming at optimizing CS nanocarriers in view of clinical applications.

Inguinal lymphadenectomy for stage III melanoma: a comparative study of two surgical approaches at the onset of lymphoedema.

INTRODUCTION: When sentinel lymph node is positive for metastasis (exclusion for micro-metastasis) and in cases of palpable adenopathy, a lymphadenectomy should be performed. Many incisional surgical approach have been described in literature. We perform two type of incision (vertical with skin excision and transversal) for inguinal lymphadenectomy. The aim of this study was to compare post-operative morbidity between these two approach in cases of Stage III Melanoma. We analysed chronic lymphoedeme, skin necrosis, wound dehiscence, wound infection and seroma rates between the two techniques. METHODS: From April 2000 to February 2012 fifty-three patients underwent to inguinal lymphadenectomy for Stage III melanoma at CHU of Rennes. Patients were stratified in 2 groups according to the surgical approach, group 1 with a vertical incision with skin excision and group 2 with a transverse incision. RESULTS: Chronic lymphoedema rate for group 1 was 37.04% and for group 2 rate was 26.92%, this complication was lower un group 2 but no significant difference was observed (p = 0.558). Skin necrosis (p = 0.235), wound dehiscence (p = 1.000), wound infection (p = 0.236) and seroma (p = 0.757) were not significantly different. Two cases of skin necrosis were observed in group 2 (7.69%) and none in group 1. CONCLUSION: We do not found significant difference for chronic lymphoedema between these two approach. However, we had less lymphoedema with the transversal technique which has the advantage to reduce the skin suffering when external iliac lymphadenectomy dissection is necessary in addition to the inguinal lymphadenectomy.

The ALPPS procedure for hepatocellular carcinoma.

BACKGROUND: The main limiting factor to major hepatic resections is the amount of the future liver remnant (FLR). Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy (ALPPS) is a procedure which induces a rapid hypertrophy of the FLR in patients with non-resectable liver tumours. METHODS: ALPPS is a surgical technique of in-situ splitting of the liver along the main portal scissura or the right side of the falciform ligament, in association with portal vein ligation in order to induce a rapid hypertrophy of the left FLR. RESULTS: The median FLR volume increase was 18.7% within one week after the first step and 38.6% after the second step. At the first step the median operating time was 300 min, blood transfusions were not required in any case, median blood loss was 150 cc. At the second step median operating time was 180 min, median blood loss was 50 cc, none of the patients required intra-operative blood. All patients are alive at a median follow up of 9 months. CONCLUSIONS: This novel strategy seems to be feasible even in the context of a cirrhotic liver, and demonstrates the capacity to reach a sufficient FLR within a shorter interval of time.

Arm vein as an alternative autogenous conduit for infragenicular bypass in the treatment of critical limb ischaemia: a 15 year experience.

OBJECTIVES: The value of alternative autogenous venous conduits for treating critical limb ischaemia (CLI) with infragenicular bypass surgery is well established. In this study, the results of using arm veins as alternative conduits for treating CLI over a 15-year period have been evaluated. METHODS: This was a retrospective study. Between 1991 and 2005. 120 infragenicular bypasses using arm vein conduits (AVCs) were performed in 120 patients. CLI was the main indication (87.5%) for the procedures. The indications for using arm veins were inadequacy or absence of the ipsilateral greater saphenous vein (GSV). Survival, limb salvage, and patency rates were calculated using the Kaplan-Meier method. RESULTS: There was a predominance of male gender (65%), and the group mean age was 68.1 ± 8.3 years. The mean follow-up period was 29.6 ± 26.3 months. The operative mortality (30 days) rate was 7.5%. The main alternative conduit was non-spliced cephalic vein (37.5%). Composite grafts included GSV + AVC (45.2%), AVC + AVC (43.3%) and small saphenous vein + AVC (11.5%). The 5-year primary and secondary patency (SP) rates were 45.2 ± 5.6% and 56.5 ± 5.0%, respectively. The 5-year SP rate was greatest when using non-spliced cephalic vein (65.8 ± 7.6%), but there was no difference in cumulative patency between spliced and non-spliced veins (49.5 ± 8.0% vs. 61.2 ± 6.4%; p = 0.501). The 5-year limb salvage and survival rates were 70.6 ± 5.9% and 59.6 ± 5.8%, respectively. CONCLUSIONS: The favourable long term results of secondary patency and limb salvage rates encourage the use of arm veins as alternative conduits for infragenicular bypass surgery.

Ionic polymeric micelles based on chitosan and fatty acids and intended for wound healing. Comparison of linoleic and oleic acid.

Chitosan is well known for its positive properties in wound healing. Also unsaturated fatty acids are described as able to accelerate tissue repairing mechanisms. In this work hydrophobically modified chitosan was obtained by ionic interaction with either oleic or linoleic acid. In aqueous environment self-assembling into nanoparticles occurred. The presence of hydrophobic domains, similar to those present in polymeric micelles, was demonstrated by changes in pyrene spectra. Both oleate and linoleate derivatives showed mucoadhesion behaviour. Cytotoxicity tests on human dermal fibroblasts demonstrated good biocompatibility of especially oleate derivatives. Clarithromycin, a poorly soluble model drug proposed for use in infected wounds was successfully encapsulated in both oleic and linoleic based polymeric micelles. The ionic structure of the carriers is responsible for their loosening at neutral pH and in the presence of salts. This behaviour should impair parenteral administration of the systems, but can be useful for topical delivery where the micelle components, chitosan and fatty acid, can play a positive role in dermal regeneration and tissue repairing.

"Sponge-like" dressings based on biopolymers for the delivery of platelet lysate to skin chronic wounds.

The aim of the present work was the development of sponge-like dressings, obtained by freeze-drying, based on chitosan glutamate and sodium hyaluronate for platelet lysate (PL) delivery to chronic skin wounds. A first phase of the research focused on the choice of the best dressing composition to obtain formulations endowed with the desired mechanical and hydration properties. In particular glycine amount (cryoprotectant agent), and water content were considered as formulation variables. The addition of glycerophosphate, used to solubilize chitosan at pH close to neutrality, was also investigated. In the second phase of the research, dressings were loaded with different amounts of PL. The influence of freeze-drying process and of excipients on the biological activity of platelet growth factors was investigated by means of a cell proliferation test using human fibroblasts. PDGF AB (platelet derived growth factor) content was assayed by means of ELISA test. Depending on composition, dressings showed different mechanical and hydration properties that make them suitable to wounds with different exudate amounts. Both freeze-drying process and excipients employed did not disturb the activity of platelet growth factors. The dressings loaded with platelet lysate were characterized by % proliferation values on fibroblast cell comparable to those observed for the fresh hemoderivate. The PDGF AB assay confirmed the results obtained from cell proliferation test.

Expanded criteria for hepatocellular carcinoma after liver transplantation: a 20-year evolution.

BACKGROUND/AIM: Milan Criteria (MC) consent excellent survivals for hepatocellular carcinoma (HCC) after liver transplantation (LT). However, several new expanded criteria were proposed, with the intent to increase the HCC patients eligible for LT, maintaining acceptable recurrence rates. The aim of the present study was to analyze a cohort of HCC patients, evaluating the evolutions in its management during the last 20 years and comparing the disease-free survivals among three different periods. METHODOLOGY: HCC patients (n = 122) were transplanted and stratified in three periods: 1st (1988-1998, liberal selection), 2nd (1999-2003, use of MC) and 3rd (2004-2008, use of UCSF criteria). The three periods were analyzed and their survivals were compared. RESULTS: Statistical differences were reported at univariate analysis regarding to both dimensional (total tumor diameter) and biological (alpha feto-protein, microvascular invasion) HCC features. Comparing the 5-year survival rates, a progressive increase was observed in the three periods (62.6%, 87.9% and 88.4%, respectively), with a significant difference between 1st and the second periods (p = 0.008). CONCLUSIONS: In our experience, use of UCSF criteria is safe, with a contemporaneous increased number of transplants and better survivals. Introduction of new selection criteria, also based on biological features, is on the way.