First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial).

BACKGROUND: The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICIs) in humans and causally implicated in ICI responsiveness in animal models. Two recent human trials demonstrated that fecal microbiota transplant (FMT) from ICI responders can rescue ICI responses in refractory melanoma, but FMT has specific limitations to scaled use. PATIENTS AND METHODS: We conducted an early-phase clinical trial of a cultivated, orally delivered 30-species microbial consortium (Microbial Ecosystem Therapeutic 4, MET4) designed for co-administration with ICIs as an alternative to FMT and assessed safety, tolerability and ecological responses in patients with advanced solid tumors. RESULTS: The trial achieved its primary safety and tolerability outcomes. There were no statistically significant differences in the primary ecological outcomes; however, differences in MET4 species relative abundance were evident after randomization that varied by patient and species. Increases in the relative abundance of several MET4 taxa, including Enterococcus and Bifidobacterium, taxa previously associated with ICI responsiveness, were observed and MET4 engraftment was associated with decreases in plasma and stool primary bile acids. CONCLUSIONS: This trial is the first report of the use of a microbial consortium as an alternative to FMT in advanced cancer patients receiving ICI and the results justify the further development of microbial consortia as a therapeutic co-intervention for ICI treatment in cancer.

Desmineralización de la Dentina Humana Producida por Irrigantes Endodónticos Combinados

El objetivo de este trabajo fue evaluar el efecto de soluciones de irrigación endodónticas solas y combinadas sobre iones calcio y fosfato de la dentina radicular ex vivo. Se emplearon 56 discos de dentina obtenidos del tercio medio radicular de premolares inferiores unirradiculares extraídos por razones ortodóncicas. Los discos se dividieron al azar en 8 grupos (n=7). Grupo I: agua destilada (AD), Grupo II: hipoclorito de sodio (NaClO) 1 %, Grupo III: EDTA 17 %, Grupo IV: ácido maleico (AM) 5 %, Grupo V: ácido acético (AA) 5 %, Grupo VI: EDTA 17 % + NaClO 1 %, Grupo VII: AM 5 % + NaClO 1 %, Grupo VIII: AA 5 % + NaClO 1 %. Los segmentos de dentina permanecieron en contacto a 37° C durante 5 min y 2,5 minutos en cada solución cuando se usaron en forma sucesiva. Se determinó la concentración de iones calcio de las soluciones mediante espectrometría de absorción atómica y la concentración de iones fosfatos mediante colorimetría (Wienner Lab.). Los resultados se expresaron en mg/ml/gr de tejido. Para el análisis estadístico se utilizó ANOVA y Test de Tukey. AA 5 % y EDTA 17 % se comportaron de manera similar utilizados solos durante 5 minutos, NaClO 1 % no mostró diferencias con el AD. AM 5 % eliminó significativamente más calcio y fosfato que todos los grupos. Todas las soluciones desmineralizaron la dentina, pero AM 5 % durante 5 min fue la solución que más afectó el componente inorgánico de la dentina.

The aim of the present study was to evaluate ex vivo irrigating solutions effect under calcium and phosphates dentin ions, using them alone and combined. In this study 56 dentin discs where used. They were obtained from middle third of mandibular single-root premolars extracted for orthodontics reasons. Discs were randomly divided into 8 groups (n:7). Group I: Distilled water (DW), Group II: 1 % sodium hypochlorite (NaOCl), Group III: 17 % EDTA, Group IV: 5 % maleic acid (MA), Group V: 5 % acetic acid (AA), Group VI: 17 % EDTA + 1 % NaOCl, Group VII: 5 % MA + 1 % NaOCl, Group VIII: 5 % AA + 1 % NaOCl. Dentin segments were kept in contact with irrigating solutions at 37°C for 5 minutes, when used alone, or for 2.5 minutes when used combined. After that, calcium ions (using absorption atomic spectrometry) and phosphorus ions (by colorimetry Wienner Lab.) were determined. Results were expressed in mg/ml/g tissue. Statistical analysis was performed by ANOVA and Tukey test. 5 % AA and 17 % EDTA eliminated similar concentrations of calcium and phosphates ions from dentin at 5 minutes exposure time, while 1 % NaOCl did not present statistical differences with control. 5 % MA eliminated significantly more calcium and phosphates ions than the rest of analyzed groups. Every tested solutions demineralized human dentin, but 5 % MA used for 5 minutes did it the most.

Megaprosthesis in articular fractures of the lower limbs in fragile patients: a proposal for the therapeutic algorithm.

OBJECTIVE: The use of megaprosthetic implants could provide substantial advantages in elderly population affected by complex fractures. The aim of the study was to identify the patients suitable to megaprosthetic implants in the treatment of lower limbs fractures, as well as periprosthetic fractures. PATIENTS AND METHODS: From January 1st, 2015, to December 31st, 2021, all patients affected by femoral fractures with severe bone loss or previous surgery failure were retrospectively reviewed. ADL, IADL, SF-12 values pre- and post-operative were recorded. Hemoglobin value, NLR, PLR were recorded pre- and peri-operatively for all patients. Complications were recorded. All patients underwent a radiological follow-up. Significance was set at p ≤ 0.05. RESULTS: 23 patients were considered eligible, 10 males and 13 females; the mean age was 72.87 years old (± 12.33), while the mean BMI was 27.2 points (± 5.2). The mean follow-up was 2 years (± 1.4). The mean preoperative ADL and IADL scores were correlated with a positive independence of the patient, while the mean postoperative scores corresponded to a moderate-low independence. Also the mean Mental and Physical SF12 scores saw a decrease in values. NLR values were higher in the first group of patients with complications. CONCLUSIONS: A careful multiparametric and multidisciplinary patient selection is required to identify the suitable patient to this treatment.

Survivorship of proximal femoral replacement in neoplastic and non-neoplastic elderly patients.

OBJECTIVE: Massive bone loss is a serious problem in the elderly. Joint replacement with modular prostheses represents the most common reconstructive technique after oncological and non-oncological resections. Megaprostheses are broadly available, adaptable and versatile and allow early mobilization and rehabilitation. Although segmental endoprosthetic implants are now widely used and despite innovations, complications remain far high. Our purpose is to establish what happens to megaprostheses of a specific anatomical site in the long term in a population with oncologic and non-oncologic indications treated at a single center solely by a few skilled surgeons. MATERIALS AND METHODS: We retrospectively reviewed our institutional database. We collected 35 patients who underwent endoprosthetic reconstruction exclusively of the proximal femur for neoplastic and non-neoplastic disease between 2008 and 2021. The minimum follow-up was 12 months. Complications were collected and classified, and also adapted to the non-oncological setting. RESULTS: Taking into consideration the entire population, 94% of this survived the follow-up at 6 months, subsequently 85% at 1 year and 82% at 2 years. At follow-ups after 5 years, 79% of megaprostheses showed no mechanical failure. Analyzing prosthetic survival in the two groups, this was >50% at 24 months after surgery in both groups, with better survival for the oncological one. CONCLUSIONS: Proximal femur replacement can be a valid option in treatment of oncological and non-oncological cases. Due to the high complication rate, only selected cases should undergo this kind of surgical procedure.

Could Duodenal Molecular Mechanisms be Involved in the Hypocholesterolemic Effect of Silicon Used as Functional Ingredient in Late-Stage Type 2 Diabetes Mellitus?

SCOPE: Hypercholesterolemia increases the risk of mortality in type 2 diabetes mellitus (T2DM), especially in the late-stage. Consumption of bioactive compounds as functional ingredients would help achieve therapeutic goals for cholesterolemia. Silicon has demonstrated a hypocholesterolemic effect and the ability to reduce fat digestion. However, it is unclear whether silicon exerts such effect in late-stage T2DM (LD) and the intestinal mechanisms involved. METHODS AND RESULTS: Three groups of eight rats were included: early-stage T2DM control (ED), LD, and the LD group treated with silicon (LD-Si) once the rats were diabetic. Morphological alterations of the duodenal mucosa, and levels of markers involve in cholesterol absorption and excretion, beside cholesterolemia, and fecal excretion were assayed. Silicon included as a functional ingredient significantly reduces cholesterolemia in part due to: 1) reducing cholesterol intestinal absorption by decreasing the absorptive area and Acetyl-Coenzyme A acetyltransferase-2 (ACAT2) levels; and 2) increasing cholesterol excretion to the lumen by induction of the liver X receptor (LXR) and consequent increase of adenosine triphosphate-binding cassette transporter (ABCG5/8). CONCLUSIONS: These results provide insight into the intestinal molecular mechanisms by which silicon reduces cholesterolemia and highlights the efficacy of the consumption of silicon-enriched functional foods in late-stage T2DM.

Phase I, first-in-human study of MSC-1 (AZD0171), a humanized anti-leukemia inhibitory factor monoclonal antibody, for advanced solid tumors.

BACKGROUND: Activation of leukemia inhibitory factor (LIF) is linked to an immunosuppressive tumor microenvironment (TME), with a strong association between LIF expression and tumor-associated macrophages (TAMs). MSC-1 (AZD0171) is a humanized monoclonal antibody that binds with high affinity to LIF, promoting antitumor inflammation through TAM modulation and cancer stem cell inhibition, slowing tumor growth. In this phase I, first-in-human, open-label, dose-escalation study, MSC-1 monotherapy was assessed in patients with advanced, unresectable solid tumors. MATERIALS AND METHODS: Using accelerated-titration dose escalation followed by a 3 + 3 design, MSC-1 doses of 75-1500 mg were administered intravenously every 3 weeks (Q3W) until progression or unmanageable toxicity. Additional patients were enrolled in selected cohorts to further evaluate safety, pharmacokinetics (PK), and pharmacodynamics after escalation to the next dose had been approved. The primary objective was characterizing safety and determining the recommended phase II dose (RP2D). Evaluating antitumor activity and progression-free survival (PFS) by RECIST v1.1, PK and immunogenicity were secondary objectives. Exploratory objectives included pharmacodynamic effects on circulating LIF and TME immune markers. RESULTS: Forty-one patients received treatment. MSC-1 monotherapy was safe and well tolerated at all doses, with no dose-limiting toxicities. The maximum tolerated dose was not reached and the RP2D was determined to be 1500 mg Q3W. Almost half of the patients had treatment-related adverse events (TRAEs), with no apparent trends across doses; no patients withdrew due to TRAEs. There were no objective responses; 23.7% had stable disease for ≥2 consecutive tumor assessments. Median PFS was 5.9 weeks; 23.7% had PFS >16 weeks. On-treatment changes in circulating LIF and TME signal transducers and activators of transcription 3 signaling, M1:M2 macrophage populations, and CD8+ T-cell infiltration were consistent with the hypothesized mechanism of action. CONCLUSIONS: MSC-1 was very well tolerated across doses, with prolonged PFS in some patients. Biomarker and preclinical data suggest potential synergy with checkpoint inhibitors.

Unopposed estrogens: current and future perspectives.

Estrogens and progestogens act on female reproductive tissues in opposite ways. As they counteract each other actions, the correct balance between these two classes of hormones is pivotal to avoid dangerous states. Unopposed estrogens occur when progestogen levels do not balance estrogens, primarily deriving from overproduction of estrogens via aromatase enzyme. In the endometrium, unopposed estrogens induce proliferative or invasive phenomena, which represent the first step toward different diseases. These pathologies include endometrial hyperplasia, endometrial polyps, endometriosis and adenomyosis. Endometrial hyperplasia and polyps are proliferative pathologies, while endometriosis and adenomyosis are characterized by the invasion of other tissues by endometrial cells. Current pharmacological treatments include Gonadotropin-Releasing-Hormone analogs, aromatase inhibitors and progestogens, either alone or in combination with estrogens. As these drugs usually lead to burdensome undesired effects, researchers seek to find new therapeutical molecules. Recent literature highlights the positive effects of metformin, an insulin sensitizing drug that reduces the insulin proliferative stimulus on the endometrium. d-chiro-inositol is an insulin second messenger with insulin sensitizing and mimetic properties, recently described as an aromatase down-regulator. Based on current evidence, d-chiro-inositol may be useful to treat the pathologies responsive to unopposed estrogens.

The potential role of imaging techniques in avoiding neck dissection during salvage surgery after head and neck carcinoma treated with bioradiotherapy.

OBJECTIVE: This study aimed to evaluate the effectiveness of computed tomography and positron emission tomography-computed tomography prior to salvage surgery after head and neck carcinoma treated with bioradiotherapy and to look at the role of neck dissection in this setting. METHOD: This study was a retrospective chart review of a series of consecutive patients with locally advanced head and neck squamous cell carcinoma treated with bioradiotherapy. Radiological and pathological stages were compared to evaluate the accuracy of computed tomography and positron emission tomography-computed tomography in detecting occult neck metastasis in the context of recurrence of primary tumour. In order to assess the impact of neck dissection on survival, Kaplan-Meier survival curves after salvage surgery with and without neck dissection were derived. RESULTS: A total of 268 patients were identified, of which 22 underwent salvage surgery. The negative predictive value of computed tomography and positron emission tomography-computed tomography was excellent. Neck dissection did not represent an improvement on overall, disease specific and regional recurrence free survival (p = 0.67, p = 0.91 and p = 0.62, respectively) amongst clinically and radiologically negative necks. CONCLUSION: Conservative treatment of the neck should be considered when dealing with patients with primary site recurrence or persistent disease after bioradiotherapy without evidence of neck disease.

Bioassay-based ecotoxicological investigation on marine and freshwater impact of cigarette butt littering.

Despite representing an extremely relevant portion (20-40%) of worldwide coastal litter, cigarette butts are still an underestimate environmental issue of limited scientific interest. Public authorities of different countries promote active removal of cigarette butts, but the issue remains problematic in terms of aesthetic, environmental and health-related impacts. There are few studies on the environmental side-effects of smoked cigarette butt litter despite being a worldwide issue. In this work, two ecotoxicological bioassay batteries were adopted to evaluate the environmental consequences of cigarette butt water-soluble ingredient release in both marine water and freshwater. Marine assays were generally more affected compared to freshwater. Interesting outcomes were observed with crustacean tests, showing a lower effect of smoked cigarette butt leachate when tested at maximum concentration. This finding were supported by heartbeat measures of Daphnia magna, which were accelerated at 100% of smoked cigarette butt leachate.

Innovations in prevention of infections in oncological megaprostheses: a narrative review.

Infection is a significant complication in oncological megaprostheses. The purpose of our study is to indagate the innovations and new trend about the prevention of infection in this kind of surgery. The research focused on the use of antimicrobic prophylaxis, the defensive antibacterial coating and the use of silver coated.

Carob fruit extract-enriched meat improves pancreatic beta-cell dysfunction, hepatic insulin signaling and lipogenesis in late-stage type 2 diabetes mellitus model.

The inclusion of functional bioactive compounds of dietary fiber in meat products has been demonstrated to exert a significant impact on human health. Carob fruit extract (CFE) is a dietary fiber rich in proanthocyanidins with known antioxidant, hypolipidemic and hypoglycemic effects. Consumption of CFE-enriched meat (CFE-RM) may provide interesting benefits in late-stage type 2 diabetes mellitus (T2DM). To explore the antidiabetic mechanisms of CFE-RM, we used a model of late-stage T2DM in Wistar rats fed a high-saturated-fat/high-cholesterol diet (Chol-diet) and injected streptozotocin plus nicotinamide (D group). The effects of CFE-RM were tested by incorporating it into the diet as preventive strategy (ED group) or curative treatment (DE group). CFE-RM had a positive effect on glycemia, enhancing hepatic insulin sensitivity and improving pancreatic ß-cell regeneration in both ED and DE groups. Western blotting and immunohistochemistry suggested that CFE-RM increased levels of insulin receptor ß and phosphatidylinositol-3-kinase, as well as the downstream target phospho-Akt (at Ser473). CFE-RM also up-regulated glucose transporter 2, which improves the insulin-mediated glucose uptake by the liver, and promoted phosphorylation of glycogen synthesis kinase-3ßprotein (at ser9), consequently increasing the hepatic glycogen content. In addition, CFE-RM decreased fatty liver by suppressing de novo lipogenesis activation due to down-regulation of liver X receptor-α/ß, sterol regulatory element binding protein-1c and carbohydrate-response element-binding protein transcription factors. Our findings suggest that the consumption of CFE-RM included in the diet as a functional food should be considered as a suitable nutritional strategy to prevent or manage late-stage T2DM.

A rare case of post-traumatic infected pilomatricoma of the finger of the hand diagnosed after performing radioiodine therapy.

We present the clinical case of a young woman with pilomatricoma of the finger, a very rare location. The patient got infected after receiving radioiodine therapy to treat a thyroid carcinoma. Given the patient's high functional requirements we choose a minimal treatment which allowed her to maintain a sufficient functionality.

Predictable risk factors for infections in proximal femur fractures.

Proximal femur fractures are increasing, together with the aging of world population. One of the complications worsening this condition is infection. In this study, we try to identify risk factors that can lead to infection. We identified 122 patients with femoral neck fracture. The occurrence of infectious events were recorded (respiratory, urinary, superficial wound and periprostethic infection). There were 15 infections, mostly urinary and pulmonary, and all were treated using antibiotics. No statistical differences were found between infection and control group regarding waiting time for surgery, mean time of surgery, age, kind of fracture, type of surgery. Fever onset >38° within 72 hours from surgery was statistically correlated with early infections. Future studies must be led to identify risk factors for infection and to create a strategy to prevent this possibly lethal complication.

The use of knee mega-prosthesis for the management of distal femoral fractures: A systematic review.

INTRODUCTION: Distal femur fractures (DFFs) are unusual and difficult to deal, especially in elderly patients. A consensus about a gold-standard treatment has not been reached yet. Available options include both conservative and surgical management. In elderly patients a prosthetic replacement could be a valid treatment option. Literature is lacking about the use of mega-prosthesis in this type of fractures. The purpose of the present systematic review is to examine which fracture, both acute and chronic, involving distal femur should be treated by using a mega-prosthesis. MATERIALS AND METHODS: Studies were identified by searching electronic databases. All studies that enrolled people of any age affected by a DFFs treated by using a megaprosthesis were included. Primary outcomes of the present reviews were: ROM, functional assessment and complications. Two review authors independently selected eligible trials. Disagreements at any stage were resolved by consensus or a third party adjudication. Descriptive statics was used to summarize the data. RESULTS: Thirteen article were finally included in the review. One hundred-four patients were treated with knee megaprosthesis. Three categories of patients were identified: 29 patients were affected by supracondylar femur fracture; 51 patients occurred with a periprosthetic fracture; 24 patients suffered a non-union of a previous supracondylar fracture. The follow-up varied between 6 months to 58 months. All studies showed good results in terms of improving quality of life, resuming activities of daily living (ADLs), early mobilization, ROM, shorter hospital stay. Although not frequent, the only reported complications were infection and aseptic loosening. DISCUSSION: The present review showed that the use of knee megaprosthetic implants could represent a valid treatment option aiming to reduce patients' immobilitazion and hospital stay. Good clinical outcomes with low rate of complications were reported by all included studies. Literature is lacking about long-term outcomes and complications. Moreover studies comparing knee prostheses and other types of surgical treatment (intramedullary nails, plate fixation system) are needed. CONCLUSIONS: Megaprosthesis represent a viable treatment option in patients affected by DFFs (either acute, periprostethic or non-union) because they allow immediate weight-bearing, shorter hospital stay, a fast recovery of knee function and ADLs.

Paronychia argentea Lam. protects renal endothelial cells against oxidative injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Paronychia argentea Lam. (Arabic tea), a species spontaneously growing in the Mediterranean area, has been used in folk medicine for renal diseases. AIM OF THE STUDY: To assess the antioxidant and protective potentials of different extracts from P. argentea in the renal endothelial NRK-52E cell line by several in vitro models, including a H2O2-induced oxidative stress model. MATERIAL AND METHODS: Aerial parts of P. argentea were collected in Algeria and ethanolic, chloroform and aqueous-chloroform extracts were obtained from dried plant. The antioxidant capacity was first evaluated by the Oxygen Radical Absorbance Capacity (ORAC) and the free radical scavenging activity (DPPH) methods. Cellular viability was assessed by MTT method assay after 24 h pretreatment with each extract concentration in order to measure protection from H2O2 in NRK-52E cells. Furthermore, the intracellular ROS formation (DCFH-DA method), was determined. RESULTS: P. argentea showed in vitro antioxidant activity as evidenced by the ORAC and DPPH assays. No cell toxicity was observed for concentrations ranging from 0.1 to 100 µg/mL of each extract. These extracts also exerted a protective effect on renal endothelial cells simultaneously treated with 1 mM H2O2. Chemical composition for the aqueous-chloroform extract was assessed by HPLC, as it showed the strongest antioxidant ability, revealing three quercetin derivatives as the main phenolic compounds. CONCLUSION: P. argentea is endorsed with antioxidant activity and protects renal endothelial cells against oxidative damage which indicate this plant constitutes a potential treatment for renal diseases.

Efficacy of the synergic action of myoinositol, tyrosine, selenium and chromium in women with PCOS.

OBJECTIVE: The aim of the study is to investigate the efficacy of a treatment with myoinositol plus L-tyrosine, selenium, and chromium in women with polycystic ovarian syndrome (PCOS). PATIENTS AND METHODS: One hundred and eighty-six women, with diagnosis of PCOS, were divided in four groups according to their clinical features. Phenotype A: androgen excess + ovulatory dysfunction + polycystic ovarian morphology. Phenotype B: androgen excess + ovulatory dysfunction. Phenotype C: androgen excess + polycystic ovarian morphology. Phenotype D: ovulatory dysfunction + polycystic ovarian morphology. All patients were given daily for six months a compound with 2 g myo-inositol, 0.5 mg L-Tyrosine, 0.2 mg folic acid, 55 mcg selenium, 40 mcg chromium. Hormonal assessment, BMI, Ferriman-Gallway Gallway score, HOMA index, and follicular monitoring were reported before starting the therapy, three months and six months after. RESULTS: Phenotype A showed an improvement, consistent with restored ovulation: more regular length of the menstrual cycle, detection of periovulatory follicle at ultrasound, and rising of progesterone in the luteal phase. A total of 45 patients (65.2%) ovulated after six months. In the same period glucose and HOMA index decreased. In the phenotype B, 80% of patients ovulated after six months. An improvement of the clinical and biochemical sign of hyperandrogenism was also reported. In the phenotype C, after BMI had followed the treatment for six months, it decreased in a statistically significant manner. In the phenotype D, 49 out of 82 women (59.7%) restored their regular menstrual period and ovulated. CONCLUSIONS: Our study reported how the synergistic action of myoinositol, L-tyrosine, selenium, and chromium could restore normal menstrual cycle, ovulation, and decrease weight in these patients.

Ag Nanoparticles/α-Ag2WO4 Composite Formed by Electron Beam and Femtosecond Irradiation as Potent Antifungal and Antitumor Agents.

The ability to manipulate the structure and function of promising systems via external stimuli is emerging with the development of reconfigurable and programmable multifunctional materials. Increasing antifungal and antitumor activity requires novel, effective treatments to be diligently sought. In this work, the synthesis, characterization, and in vitro biological screening of pure α-Ag2WO4, irradiated with electrons and with non-focused and focused femtosecond laser beams are reported. We demonstrate, for the first time, that Ag nanoparticles/α-Ag2WO4 composite displays potent antifungal and antitumor activity. This composite had an extreme low inhibition concentration against Candida albicans, cause the modulation of α-Ag2WO4 perform the fungicidal activity more efficient. For tumor activity, it was found that the composite showed a high selectivity against the cancer cells (MB49), thus depleting the populations of cancer cells by necrosis and apoptosis, without the healthy cells (BALB/3T3) being affected.

Hip megaprosthesis in oncological surgery: open questions.

Prosthetic replacement with modular implants has become the most common reconstructive tech¬nique of bone loss of the lower limb after tumour resection. The use of the megaprosthesis in bone metastasis, silver-coated megaprosthesis and the use of Trevira tube are not uniform and represent an "open question" about the use of megaprosthesis. The following paper aims to review the current literature in this topic.

Masquelet technique and osteomyelitis: innovations and literature review.

OBJECTIVE: Wide diaphyseal bone defects, above all those infected, encounter into Masquelet technique a suitable treatment. The two-step procedure allows the surgeon to eliminate the infected tissues and then to promote new bone formation. We analyzed the literature about the use of the induced membrane technique in osteomyelitis and the innovations recently suggested. MATERIALS AND METHODS: We reviewed some of the most common web databases using the key-words: Masquelet technique, induced membrane, and osteomyelitis. 66 studies were analyzed. RESULTS: Comparing the Masquelet technique to other surgical procedures it shows better functional results in large bone defects due to infection. The induced membrane is like a biological chamber that protects the autograft and induces new bone formation promoting growth factors secretion. Different authors tried to improve one or more steps of the surgical procedure. Some studies focused on polymethyl methacrylate role and the possibility to use different materials instead of cement to induce the membrane. Others analyzed the autograft harvesting and placing techniques trying to reduce the amount of bone essential to fill the gap, like the RIA technique. Moreover, bone substitutes have been used, as beta-tricalcium phosphate, that showed an osteoconductive ability. CONCLUSIONS: The survey is not a systematic review. Nevertheless, new concepts are introduced and analyzed identifying 6 areas of interest and induced membrane technique development.