Genetic profiling using plasma-derived cell-free DNA in therapy-naïve hepatocellular carcinoma patients: a pilot study.

Background: Hepatocellular carcinomas (HCCs) are not routinely biopsied, resulting in a lack of tumor materials for molecular profiling. Here we sought to determine whether plasma-derived cell-free DNA (cfDNA) captures the genetic alterations of HCC in patients who have not undergone systemic therapy. Patients and methods: Frozen biopsies from the primary tumor and plasma were synchronously collected from 30 prospectively recruited, systemic treatment-naïve HCC patients. Deep sequencing of the DNA from the biopsies, plasma-derived cfDNA and matched germline was carried out using a panel targeting 46 coding and non-coding genes frequently altered in HCCs. Results: In 26/30 patients, at least one somatic mutation was detected in biopsy and/or cfDNA. Somatic mutations in HCC-associated genes were present in the cfDNA of 63% (19/30) of the patients and could be detected 'de novo' without prior knowledge of the mutations present in the biopsy in 27% (8/30) of the patients. Mutational load and the variant allele fraction of the mutations detected in the cfDNA positively correlated with tumor size and Edmondson grade. Crucially, among the seven patients in whom the largest tumor was ≥5 cm or was associated with metastasis, at least one mutation was detected 'de novo' in the cfDNA of 86% (6/7) of the cases. In these patients, cfDNA and tumor DNA captured 87% (80/92) and 95% (87/92) of the mutations, suggesting that cfDNA and tumor DNA captured similar proportions of somatic mutations. Conclusion: In patients with high disease burden, the use of cfDNA for genetic profiling when biopsy is unavailable may be feasible. Our results support further investigations into the clinical utility of cfDNA in a larger cohort of patients.

Safety and efficacy of subcutaneous hepatitis B immunoglobulin after liver transplantation: an open single-arm prospective study.

Life-long hepatitis B immunoglobulin (HBIG) administration is a main component of prophylactic strategy to prevent hepatitis B virus (HBV) reinfection after liver transplantation (LT). Long-term effects of HBIG treatment are known only for intravenous (IV) and intramuscular formulations. To evaluate safety and efficacy of self-administered SC HBIG, 135 LT patients receiving a 48-week treatment were analyzed. The dose of HBIG was 500 IU or 1000 IU if body weight was <75 kg or ≥75 kg, respectively. Patients were switched from the monthly IV HBIG treatment to weekly SC HBIG 2-3 weeks after the last IV dosage. All patients were able to SC self-injection after a single training. The treatment was effective in maintaining trough anti-HBs levels >100 IU/L. No severe drug-related side effects occurred. Fifteen injection-site small hematomas and four cases of mild itch occurred. At the end of the study, anti-HBs median titer was 232 IU/L (115-566 IU/L) and 97.8% of patients had an anti-HBs level >150 IU/L. Due to high mean level of anti-HBs titers observed during this study, individualized treatment schedules should be further investigated. In conclusion, SC HBIG for long-term prophylaxis of post-LT HBV reinfection resulted safe, well accepted, and effective in maintaining adequate anti-HBs levels.

Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis.

BACKGROUND: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. MATERIALS AND METHODS: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. RESULTS: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. CONCLUSIONS: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.

Identification of lenvatinib prognostic index via recursive partitioning analysis in advanced hepatocellular carcinoma.

BACKGROUND: After the advent of new treatment options for advanced hepatocellular carcinoma (HCC), the identification of prognostic factors is crucial for the selection of the most appropriate therapy for each patient. PATIENTS AND METHODS: With the aim to fill this gap, we applied recursive partitioning analysis (RPA) to a cohort of 404 patients treated with lenvatinib. RESULTS: The application of RPA resulted in a classification based on five variables that originated a new prognostic score, the lenvatinib prognostic index (LEP) index, identifying three groups: low risk [patients with prognostic nutritional index (PNI) >43.3 and previous trans-arterial chemoembolization (TACE)]; medium risk [patients with PNI >43.3 but without previous TACE and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage B (BCLC-B)]; high risk [patients with PNI <43.3 and ALBI grade 2 and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage C (BCLC-C)]. Median overall survival was 29.8 months [95% confidence interval (CI) 22.8-29.8 months] in low risk patients (n = 128), 17.0 months (95% CI 15.0-24.0 months) in medium risk (n = 162) and 8.9 months (95% CI 8.0-10.7 months) in high risk (n = 114); low risk hazard ratio (HR) 1 (reference group), medium risk HR 1.95 (95% CI 1.38-2.74), high risk HR 4.84 (95% CI 3.16-7.43); P < 0.0001. The LEP index was validated in a cohort of 127 Italian patients treated with lenvatinib. While the same classification did not show a prognostic value in a cohort of 311 patients treated with sorafenib, we also show a possible predictive role in favor of lenvatinib in the low risk group. CONCLUSIONS: LEP index is a promising, easy-to-use tool that may be used to stratify patients undergoing systemic treatment of advanced HCC.

Endovascular treatment of femoropopliteal stenoses/occlusions with a SilverHawk directional atherectomy device: immediate results and 12-month follow-up.

PURPOSE: This paper reports our immediate and 12-month follow-up results in the treatment of arterial stenoses/occlusions of the femoropopliteal region with the use of the SilverHawk directional atherectomy device (EV3, USA). MATERIALS AND METHODS: In an 18-month period, we treated 18 patients (13 men, five women, age range 39-81 years) with the SilverHawk directional atherectomy device. Inclusion criteria were symptomatic femoropopliteal stenosis/insufficiency, nonresponsiveness to medical therapy, and Rutherford categories 3-5. Exclusion criteria were based on the preliminary colour Doppler ultrasound (US) assessment and were plaque with a calcified component >50% and inadequate upstream and/or downstream vascular bed. Patients with severe vascular impairment, classified as TransAtlantic Inter-Society Consensus (TASC) D, were also excluded. RESULTS: The procedure was successfully completed in all cases, with evident recanalisation and sufficient wall remodelling. No major complication was observed. At assessment immediately after the procedure and over the following days, an improvement in clinical symptoms and in the Rutherford scale was observed. Follow-up at 2 and 12 months identified one case of distal reocclusion subsequently treated with amputation, and two cases of restenosis (primary patency 79%) successfully treated with a repeat procedure (secondary patency 96%). CONCLUSIONS: The SilverHawk directional atherectomy device proved to be an effective and safe tool in all our patients treated for femoropopliteal stenosis/occlusion, with a significant improvement in both imaging findings and clinical signs and symptoms.

Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience.

OBJECTIVE: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord. PATIENTS AND METHODS: This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV). RESULTS: We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days. CONCLUSIONS: Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.

The process of truth disclosure: an assessment of the results of information during the diagnostic phase in patients with cancer.

BACKGROUND: Surveys carried out in Mediterranean countries demonstrated very low rates of awareness of both diagnosis and prognosis among cancer patients. In our institution, a long-term training program aimed at improving communication skills among all physicians interacting with cancer patients was conducted. We report here the results of an extensive assessment of patients' awareness conducted after the first training period. PATIENTS AND METHODS: In a 2-year period, after every first visit of patients with a histological diagnosis of cancer, oncologists elicited perception of the patients and completed a structured questionnaire focusing on the understanding of the diagnosis and prognosis. Our data are thus a photograph of the results of the informative process conducted during the diagnostic phase. RESULTS: Among the enrolled 649 patients, 79.3% were aware of their diagnosis; factors significantly associated with higher levels of awareness were age younger than 70 and referral from surgery (versus internal medicine). Knowledge about the palliative or curative aims of future treatments (a surrogate sign of prognostic consciousness) was evident in 55.2%. CONCLUSIONS: Compared with historical data, our results show a high level of comprehension of the diagnosis of malignancy, probably due to the extensive training effort together with the method chosen for assessment.

Human fibroblasts and 900 MHz radiofrequency radiation: evaluation of DNA damage after exposure and co-exposure to 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5h)-furanone (MX).

The aim of this study was to investigate DNA damage in human dermal fibroblasts from a healthy subject and from a subject affected by Turner's syndrome that were exposed for 24 h to radiofrequency (RF) radiation at 900 MHz. The RF-radiation exposure was carried out alone or in combination with 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a well-known environmental mutagen and carcinogen produced during the chlorination of drinking water. Turner's syndrome fibroblasts were also exposed for a shorter time (1 h). A signal similar to that emitted by Global System for Mobile Communications (GSM) mobile phones was used at a specific absorption rate of 1 W/kg under strictly controlled conditions of temperature and dosimetry. To evaluate DNA damage after RF-radiation exposure alone, the alkaline comet assay and the cytokinesis-block micronucleus assay were used. In the combined-exposure experiments, MX was given at a concentration of 25 microM for 1 h immediately after the RF-radiation exposure, and the effects were evaluated by the alkaline comet assay. The results revealed no genotoxic and cytotoxic effects from RF radiation alone in either cell line. As expected, MX treatment induced an increase in DNA migration in the comet assay, but no enhancement of the MX-induced DNA damage was observed in the cells exposed to RF radiation.

Evidence of liver histological alterations in apparently healthy individuals evaluated for living donor liver transplantation.

BACKGROUND: Living donor liver transplantation (LDLT) represents an important therapeutic option for patients with end-stage liver disease (ESLD). It has been reported that steatosis may be a serious problem in patients who donate a part of their liver. Liver biopsy represents an accepted method to assess the rate of steatosis and the possible risk to the donor. Nonetheless, some histological abnormalities have been documented in the specimens from potential donors. The aim of this study was to evaluate the possible hepatic histological alterations among apparently healthy candidates for liver donation who did not show serological or ultrasound (US) evidence. MATERIALS AND METHODS: From January 1, 2005 until October 15, 2006, we performed virological, biochemical, and tumor marker evaluations and liver biopsies on 20 LDLT donor candidates. At histological evaluation we classified the evidence of steatosis (5%-10% or 10%-20%), fibrosis (absent or 1-3 portal space), inflammation, iron deposition, biliary neoductulation, and portal vein vascular alterations. RESULTS: Among the 20 subjects, serological markers did not show any pathological alterations. At liver biopsy we found: steatosis (5%-10%) in 6 individuals (about 30%) with 1 ranging from 10% to 20%; iron deposition in 4 (20%); biliary neoductulation in 3 (about 16%); fibrosis in 4 (20%); inflammation in 5 (25%); and portal vein dilatation in 10 (50%). CONCLUSIONS: Our data showed that apparently healthy individuals who did not display serological markers or US evidence of pathology had liver histological abnormalities. This result suggested that in absence of clinical or laboratory alterations, liver biopsy may represent a useful diagnostic tool for living donor candidates. Long-term follow-up results for the laboratory data among those patients should be performed even though they were not qualified for LDLT.

Acute rejection after liver transplantation: Is there a specific immunological pattern?

The aim of the study was to assess various T-cell subsets and cytokine secretion patterns both in liver tissue and in the peripheral blood of 24 liver transplant patients to assess possible specific immunological involvement in early acute rejection episodes after liver transplantation. Particularly, we studied CD4+ CD7+, CD8+ CD38+, and CD4+ CD25+ T cells by flow cytometry, as well as contemporaneously, interleukin (IL)-2 and IL-10 secretion by ELISpot to determine possible Th1-like immune responses and the immunomodulation expressed by Treg cells in acute liver rejection, respectively. As a control group we included patients transplanted without acute rejection. Early acute rejection within the first 4 weeks was proven histologically in 42% of patients. It was associated with a greater expression of CD4+ CD7+ and CD8+ CD38+ T cells in the liver than in the blood (P < .001). A contemporaneous reduced expansion of liver Treg cells was evident in patients with acute rejection (P < .001). Our data suggested that a preferential Th1-like immune mechanism operated in local fashion as characterized by a decreased presence in the liver and blood of Treg cells.

[In vivo metabolism of rat submaxillary gland phospholipids]. / Métabolisme in vivo des phospholipides de la glande sous-maxillaire de rat

The metabolism of the phospholipids of the submaxillary gland are studied after intraperitoneal injections of [32P]-orthophosphate in several groups of rats. The gland contains mainly phosphatidylcholines and phosphatidylethanolamines and in smaller quantities phosphatidylinositols, phosphatidylserines, sphingomyelins, polyglycerophosphatides, lysophosphatidylcholines and phosphatidic acids. The specific activities of the phospholipids measured in relation to the time (1/2 hour, 1, 2 and 3 hours) show a strong incorporation in the phosphatidylinositols then in the phosphatidylcholines. The other phospholipids have lower activities. The specific activities of the phospholipids measured one hour after injection of different pharmacodynamic agents show the phosphatidylinositols, phosphatidylcholines, sphingomyelins and lysophosphatidylcholines are altered. Acetylcholine increases their turnover, Atropine reduces it, and the addition of atropine counteracts the effect of acetylcholine in all these phospholipids.

Depolarizing action of GABA (gamma-aminobutyric acid) on myelinated fibers of peripheral nerves.

The inhibitory neurotransmitter GABA (gamma-aminobutyric acid) has been shown to have a depolarizing action on myelinated axons of both mammalian and amphibian peripheral nerves. In initial in vivo observations intravenous injections of GABA caused an increase in the excitability of the low-threshold, fast conducting fibers of the superficial radial and median nerves of the cat. Similar, graded, reversible effects were confirmed (using changes in the amplitude/integral of the stimulus-evoked A-fiber submaximal compound action potential to assess excitability) in in vitro studies with the isolated, desheathed frog sciatic nerve. GABA caused a mean maximal increase in half-maximal action potential of 29.8% (S.E. +/- 2.7), with an ED50 value of 0.09 mM and Hill coefficient of 0.70. This effect did not appear to desensitize, and could be reversibly antagonized by both bicuculline and picrotoxin. Comparison of agonist sensitivities showed a rank order of potency with muscimol greater than 3-aminopropanesulfonic acid greater than GABA greater than beta-guanidinopropionic acid greater than imidazole-acetic acid greater than guanidoacetic acid greater than delta-aminovaleric acid. With structure activity analysis the maximal activity was found to be related to N+-C separation near the 5 A value. Partial substitution of chloride ions in the superfusate by isethionate reversibly depressed the effect of GABA. These observations support the conclusion that extrasynaptic receptors for GABA are present on the myelinated axons of peripheral nerves.

Role of K+ in GABA (gamma-aminobutyric acid)-evoked depolarization of peripheral nerve.

Isolated, desheathed sciatic nerves of the leopard frog or bull frog were used in studies to determine different sources/components of the depolarizing effect of GABA (gamma-aminobutyric acid) on myelinated fibers. During the depolarization induced by 1 mM GABA--which was reflected by an increase of 38.3% (S.E. +/- 2.2) in the amplitude of the evoked half-maximal A-fiber compound action potential--the level of extracellular potassium ([K+]o) measured at depths less than or equal to 200 microns in the nerve with ion-selective microelectrodes, increased by 0.096 mM (S.E. +/- 0.007). Changes in excitability preceded K+]o, and there was a significant difference between their peak latencies. Artificially raised levels of [K+]o, similar to those induced by GABA, caused extremely small changes (less than 10%) in the size of the evoked action potential. From the magnitude and time course of the GABA-evoked augmentation of levels of [K+]o, it can be concluded that potassium ions probably arise indirectly and play a secondary role in what appears to be a mainly receptor-mediated depolarization of axons. A much greater sensitivity to GABA was found for fibers of the dorsal roots in comparison with those of the ventral roots (maximal changes in excitability of 50% and 6% respectively). This suggests that the depolarization of ventral root fibers could be caused by [K+]o accumulation, and that there may be a preferentially localized distribution of receptors for GABA on the sensory axons of peripheral nerve.

Diurnal changes in psychophysiological variables of school girls: comparison with regard to age and teacher's appreciation of learning.

Ninety-five nonresident girls of a private school volunteered for the study with the teachers' help as well as parental consent. Ages were approximately 8, 9, and 10 years. They were synchronized with diurnal activity from 0730 to 2100 h and nocturnal rest. Fatigue, drowsiness, and attention were self-rated using visual analogue scales; oral temperature was self-measured and a letter cancellation test was performed. Each of these variables was measured at school at 0900, 1100, 1400, and 1600 h on Mondays, Thursdays, Fridays, and Saturdays for two consecutive weeks in 1987 (March 30-April 11) and again in 1989 (March 13-25) when the youngest group had become 10 years old. According to conventional teacher evaluation of learning (learning performance) within each group, three subgroups were formed: top third, middle third, and bottom third. Time series (more than 50,000 data) were analyzed according to several statistical methods, but mainly chronograms with ANOVA. Similar diurnal changes in oral temperature were validated for each group and subgroups. The occurrence of a diurnal change in self-rated variables (fatigue and drowsiness) and score in letter cancellation was age related: no detection in the 8-year-old group (and subgroups) and validation (p less than 0.002) in 9- and 10-year-old groups (and respective subgroups). A good learning performance was associated with a reduced drowsiness in school girls of 9 and 10 years. Age-related, time-of-day differences in drowsiness (when detected) as well as learning performance effect were not associated with observed duration of sleep. Validated changes in self-rated fatigue were close to that of drowsiness. At 0900 h, girls of 9 and 10 years were more tired when belonging to the bottom third than top third subgroup. Whatever the time of day, self-rated attention was greater in the top than in the bottom third for these girls. Differences related to learning performance were validated in each grade. However, best scores were recorded for the bottom third in the 8-year-old group, while best scores were provided by top third subgroups in 10-year-old girls. It seems that in girls around 8 years of age, critical changes can be detected with regard to the (ontogenic?) occurrence of time-of-day differences in a set of psychophysiologic variables as well as influential effects of learning performance on the same variables. Reported finding are compatible with the hypothesis of circadian oscillators working at the level of the cortex of the human brain.

Weekly changes in psychophysiological variables of 8- to 10-year-old school girls.

Three groups of schoolgirls 8, 9, and 10 years of age, respectively, self assessed sleep onset/offset and duration, as well as oral temperature and a set of cognitive measures, at school at 09:00, 11:00, 14:00, and 16:00 h on Mondays, Tuesdays, Thursdays, and Fridays (and/or Saturday) for 2 consecutive weeks (spring 1987 and 1989). The scores of a letter cancellation test exhibited neither daily nor weekly temporal variation at the age of 8 years [analysis of variance (ANOVA), p > 0.05]. In contrast, in the 10-year-olds, changes as a function of both time of day (peak time 14:00-16:00 h) and day of week (peak day Tuesday-Friday) were substantiated. Moreover, the time of best performance on the letter cancellation test varied systematically according to the day of the week (ANOVA, p = 0.000). Day of the week changes in the observed duration of sleep, self-rated fatigue, drowsiness, and attention changes were not detected in any of the age groups. It is hypothesized that temporal performance variations in the girls during the 7-day period was age related.

[Prevalence of antibody to hepatitis C virus in hospital personnel]. / Prevalenza dell'anticorpo contro il virus dell'epatite C nel personale ospedaliero.

UNLABELLED: Prevalence of antibody to hepatitis C virus (anti-HCV) has been widely investigated in many categories; however no data are available on hospital personnel. The aim of our study was to investigate whether hospital personnel are at risk for HCV infection. METHODS: sera collected during a prospective study on HBV infection in hospital workers done in our institution in 1985 were analyzed for the ELISA test for anti-HCV from Ortho Diagnostic System. Sera were stored at -20 degrees C and were never defrosted until tested. A population of a consecutive series of healthy volunteer blood donors was used as a control group. RESULTS: the anti-HCV prevalence was higher in hospital personnel, than in blood donors (4.5 versus 1.1, p less than 0.001, Odds Ratio 4.5, Confidence Limits 2.9-7.2). CONCLUSION: although anti-HCV is not an "ideal" test for epidemiological purposes, our study suggests that hospital personnel is at high risk for HCV infection.

Platelet rich plasma in the treatment of bisphosphonate-related osteonecrosis of the jaw: personal experience and review of the literature.

Bisphosphonates (BPs) are a class of synthetic drugs commonly used to treat bone metastasis and various bone diseases that cause osseous fragility (such as osteoporosis). Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a common complication in patients who received BPs, especially intravenously. Recently, osteonecrosis of the jaw (ONJ) caused by chemotherapeutic not belonging to BPs drug class has been reported. For this reason, it has been proposed recently to rename BRONJ in antiresorptive agents related osteonecrosis of the jaw (ARONJ), to include a wider spectrum of drugs that may cause osteonecrosis of the jaw. The most debated topic about ARONJ/BRONJ is therapy. The most adequate procedure is far from being standardized and prevention seems to play a pivotal role. In our study, we considered 72 patients with BRONJ with nonsurgical therapy, surgical therapy, and surgical therapy with platelet rich plasma (PRP) gel to evaluate its therapeutic effect in promoting ONJ wounds healing. Good results showed by PRP in improving wound healing give away to case-control randomized studies that could give definitive evidence of its effectiveness.