Platelet-rich plasma counteracts detrimental effect of high-glucose concentrations on mesenchymal stem cells from Bichat fat pad

Diabetic patients display increased risk of periodontitis and failure in bone augmentation procedures. Mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) represent a relevant advantage in tissue repair process and regenerative medicine. We isolated MSCs from Bichat's buccal fat pad (BFP) and measured the effects of glucose and PRP on cell number and osteogenic differentiation potential. Cells were cultured in the presence of 5.5-mM glucose (low glucose [LG]) or 25-mM glucose (high glucose [HG]). BFP–MSC number was significantly lower when cells were cultured in HG compared with those in LG. Following osteogenic differentiation procedures, calcium accumulation, alkaline phosphatase activity, and expression of osteogenic markers were significantly lower in HG compared with LG. Exposure of BFP–MSC to PRP significantly increased cell number and osteogenic differentiation potential, reaching comparable levels in LG and in HG. Thus, high-glucose concentrations impair BFP–MSC growth and osteogenic differentiation. However, these detrimental effects are largely counteracted by PRP

Effectiveness of surgical procedures in the acceleration of orthodontic tooth movement: Findings from systematic reviews and meta-analyses

The current overview aimed to summarise the findings provided by systematic reviews (SRs) on the effect of surgical procedures in the acceleration of tooth movement and to assess the methodological quality of the included SRs. Three electronic databases have been explored. SRs addressing the effects of surgical procedures on the acceleration of tooth movement were included. The methodological quality of the included SRs was assessed using the updated version of “A Measurement Tool to Assess Systematic Review” (AMSTAR-2). Twenty-eight (28) SRs were included. The methodological quality of the included reviews ranged between critically low (6 studies) and high (12 studies). The most common critical weakness in the included reviews was the absence of clearly a-prior established review methods and any significant deviations from the protocol. The most studied surgical procedure was corticotomy, followed by micro-osteoperforation, piezocision and periodontally accelerated osteogenic orthodontics. The majority of the included SRs supported short-term favourable effects of corticotomy on treatment time and tooth movement rate, in the short-term. However, the authors of the included SRs reported that results were based on weak quality evidence. Conflicting results arise from the existent SRs with regards to the effectiveness of piezocision and micro-osteoperforation. Few SRs summarised complications and side effects of surgical techniques, supporting absence of loss of tooth vitality, periodontal problems, or severe root resorption. The current overview of SRs highlighted the need of high quality SRs comparing different surgical approaches for tooth movement acceleration though network meta-analysis, in order to determine the most efficient instrument for orthodontic movement acceleration

Viscous-Inviscid Interactions in a Boundary-Layer Flow Induced by a Vortex Array

In this paper we investigate the asymptotic validity of boundary layer theory. For a flow induced by a periodic row of point-vortices, we compare Prandtl's solution to Navier-Stokes solutions at different $Re$ numbers. We show how Prandtl's solution develops a finite time separation singularity. On the other hand Navier-Stokes solution is characterized by the presence of two kinds of viscous-inviscid interactions between the boundary layer and the outer flow. These interactions can be detected by the analysis of the enstrophy and of the pressure gradient on the wall. Moreover we apply the complex singularity tracking method to Prandtl and Navier-Stokes solutions and analyze the previous interactions from a different perspective

Colorectal Cancer with Peritoneal Metastases: The Impact of the Results of PROPHYLOCHIP, COLOPEC, and PRODIGE 7 Trials on Peritoneal Disease Management

HIPEC is a potentially useful locoregional treatment combined with cytoreduction in patients with peritoneal colorectal metastases. Despite being widely used in several cancer centers around the world, its role had never been investigated before the results of three important RCTs appeared on this topic. The PRODIGE 7 trial clarified the role of oxaliplatin-based HIPEC in patients treated with radical surgery. Conversely, the PROPHYLOCHIP and the COLOPEC were designed to chair the role of HIPEC in patients at high risk of developing peritoneal metastases. Although all three trials demonstrated the relative ineffectiveness of HIPEC for treating or preventing peritoneal metastases, these results are not sufficient to abandon this technique. In addition to some criticisms relating to the design of the trials and their statistical value, the oxaliplatin-based HIPEC was found to be ineffective in preventing or treating peritoneal colorectal metastases, especially in patients already treated with systemic platinum-based chemotherapy. Several studies are ongoing investigating further HIPEC drugs and regimens. The review deeply discussed all the aspects and relapses of this new evidence

10 Years of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): A Systematic Review and Meta-Analysis

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel intraperitoneal drug delivery method of low-dose chemotherapy as a pressurized aerosol in patients affected by peritoneal cancer of primary or secondary origin. We performed a systematic review and meta-analysis with the aim of assessing the feasibility, safety, and efficacy of PIPAC. Methods: A systematic literature search was performed using Medline and Web of Science databases from 1 January 2011, to inception, to 31 December 2021. Data were independently extracted by two authors. The Newcastle-Ottawa Scale was used to assess the quality and risk of bias of studies. Meta-analysis was performed for pathological response, radiological response, PCI variation along treatment, and for patients undergoing three or more PIPAC. Pooled analyses were performed using the Freeman–Tukey double arcsine transformation, and 95% CIs were calculated using Clopper–Pearson exact CIs in all instances. Results: A total of 414 papers on PIPAC were identified, and 53 studies considering 4719 PIPAC procedure in 1990 patients were included for analysis. The non-access rate or inability to perform PIPAC pooled rate was 4% of the procedures performed. The overall proportion of patients who completed 3 or more cycles of PIPAC was 39%. Severe toxicities considering CTCAE 3–4 were 4% (0% to 38.5%). In total, 50 studies evaluated deaths within the first 30 postoperative days. In the included 1936 patients were registered 26 deaths (1.3%). The pooled analysis of all the studies reporting a pathological response was 68% (95% CI 0.61–0.73), with an acceptable heterogeneity (I2 28.41%, p = 0.09). In total, 10 papers reported data regarding the radiological response, with high heterogeneity and a weighted means of 15% (0% to 77.8%). PCI variation along PIPAC cycles were reported in 14 studies. PCI diminished, increased, or remained stable in eight, one and five studies, respectively, with high heterogeneity at pooled analysis. Regarding survival, there was high heterogeneity. The 12-month estimated survival from first PIPAC for colorectal cancer, gastric cancer, gynecological cancer and hepatobiliary/pancreatic cancer were, respectively, 53%, 25%, 59% and 37%. Conclusions: PIPAC may be a useful treatment option for selected patients with PM, with acceptable grade 3 and 4 toxicity and promising survival benefit. Meta-analysis showed high heterogeneity of data among up-to-date available studies. In a subset analysis per primary tumor origin, pathological tumor regression was documented in 68% of the studies with acceptable heterogeneity. Pathological regression seems, therefore, a reliable outcome for PIPAC activity and a potential surrogate endpoint of treatment response. We recommend uniform selection criteria for patients entering a PIPAC program and highlight the urgent need to standardize items for PIPAC reports and datasets

Diagnostic and Therapeutic Algorithm for Appendiceal Tumors and Pseudomyxoma Peritonei: A Consensus of the Peritoneal Malignancies Oncoteam of the Italian Society of Surgical Oncology (SICO)

Aim: Pseudomyxoma peritonei (PMP) is an uncommon pathology, and its rarity causes a lack of scientific evidence, precluding the design of a prospective trial. A diagnostic and therapeutic algorithm (DTA) is necessary in order to standardize the disease treatment while balancing optimal patient management and the correct use of resources. The Consensus of the Italian Society of Surgical Oncology (SICO) Oncoteam aims at defining a diagnostic and therapeutic pathway for PMP and appendiceal primary tumors applicable in Italian healthcare. Method: The consensus panel included 10 delegated representatives of oncological referral centers for Peritoneal Surface Malignancies (PSM) affiliated to the SICO PSM Oncoteam. A list of statements regarding the DTA of patients with PMP was prepared according to recommendations based on the review of the literature and expert opinion. Results: A consensus was obtained on 33 of the 34 statements linked to the DTA; two flowcharts regarding the management of primary appendiceal cancer and peritoneal disease were approved. Conclusion: Currently, consensus has been reached on pathological classification, preoperative evaluation, cytoreductive surgery technical detail, and systemic treatment; some controversies still exist regarding the exclusion criteria for HIPEC treatment. A shared Italian model of DTA is an essential tool to ensure the appropriateness and equity of treatment for these patients

Analysis of the humoral and cellular immune response after a full course of BNT162b2 anti-SARS-CoV-2 vaccine in cancer patients treated with PD-1/PD-L1 inhibitors with or without chemotherapy: an update after 6 months of follow-up

Background: The durability of immunogenicity of SARS-CoV-2 vaccination in cancer patients remains to be elucidated. We prospectively evaluated the immunogenicity of the vaccine in triggering both the humoral and the cell-mediated immune response in cancer patients treated with anti-programmed cell death protein 1/programmed death-ligand 1 with or without chemotherapy 6 months after BNT162b2 vaccine. Patients and methods: In the previous study, 88 patients were enrolled, whereas the analyses below refer to the 60 patients still on immunotherapy at the time of the follow-up. According to previous SARS-CoV-2 exposure, patients were classified as SARS-CoV-2-naive (without previous SARS-CoV-2 exposure) and SARS-CoV-2-experienced (with previous SARS-CoV-2 infection). Neutralizing antibody (NT Ab) titer against the B.1.1 strain and total anti-spike immunoglobulin G concentration were quantified in serum samples. The enzyme-linked immunosorbent spot assay was used for quantification of anti-spike interferon-γ (IFN-γ)-producing cells/106 peripheral blood mononuclear cells. Fifty patients (83.0%) were on immunotherapy alone, whereas 10 patients (7%) were on chemo-immunotherapy. We analyzed separately patients on immunotherapy and patients on chemo-immunotherapy. Results: The median T-cell response at 6 months was significantly lower than that measured at 3 weeks after vaccination [50 interquartile range (IQR) 20-118.8 versus 175 IQR 67.5-371.3 IFN-γ-producing cells/106 peripheral blood mononuclear cells; P < 0.0001]. The median reduction of immunoglobulin G concentration was 88% in SARS-CoV-2-naive subjects and 2.1% in SARS-CoV-2-experienced subjects. SARS-CoV-2 NT Ab titer was maintained in SARS-CoV-2-experienced subjects, whereas a significant decrease was observed in SARS-CoV-2-naive subjects (from median 1 : 160, IQR 1 : 40-1 : 640 to median 1 : 20, IQR 1 : 10-1 : 40; P < 0.0001). A weak correlation was observed between SARS-CoV-2 NT Ab titer and spike-specific IFN-γ-producing cells at both 6 months and 3 weeks after vaccination (r = 0.467; P = 0.0002 and r = 0.428; P = 0.0006, respectively). Conclusions: Our work highlights a reduction in the immune response in cancer patients, particularly in SARS-CoV-2-naive subjects. Our data support administering a third dose of COVID-19 vaccine to cancer patients treated with programmed cell death protein 1/programmed death-ligand 1 inhibitors

Complications and Mortality Rate of Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: Italian Peritoneal Surface Malignancies Oncoteam Results Analysis

Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy may significantly improve survival for selected patients with peritoneal surface malignancies, but it has always been criticized due to the high incidence of postoperative morbidity and mortality. Methods: Data were collected from nine Italian centers with peritoneal surface malignancies expertise within a collaborative group of the Italian Society of Surgical Oncology. Complications and mortality rates were recorded, and multivariate Cox analysis was used to identify risk factors. Results: The study included 2576 patients. The procedure was mostly performed for ovarian (27.4%) and colon cancer (22.4%). The median peritoneal cancer index was 13. Overall postoperative morbidity and mortality rates were 34% and 1.6%. A total of 232 (9%) patients required surgical reoperation. Multivariate regression logistic analysis identified the type of perfusion (p ≤ 0.0001), body mass index (p ≤ 0.0001), number of resections (p ≤ 0.0001) and colorectal resections (p ≤ 0.0001) as the strongest predictors of complications, whereas the number of resections (p ≤ 0.0001) and age (p = 0.01) were the strongest predictors of mortality. Conclusions: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is a valuable option of treatment for selected patients with peritoneal carcinomatosis providing low postoperative morbidity and mortality rates, if performed in high-volume specialized centers

Immunogenicity and safety after the third dose of BNT162b2 anti-SARS-CoV-2 vaccine in patients with solid tumors on active treatment: a prospective cohort study

Background: Although a full course of coronavirus disease 2019 (COVID-19) vaccine is effective in cancer patients, the duration of the protection and the efficacy of a booster dose against the new variants remain unknown. We prospectively evaluated the immunogenicity of the third dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BNT162b2 messenger RNA vaccine in cancer patients undergoing active treatment. Patients and methods: Patients with solid cancer, vaccinated with a booster dose during active treatment, were enrolled in this study. Patients were classified into SARS-CoV-2 naïve (without previous COVID-19 infection) and SARS-CoV-2 experienced (with previous COVID-19 infection). Neutralizing antibody (NT Ab) titer and total anti-Spike immunoglobulin G (IgG) concentration were quantified in serum. Heparinized whole blood samples were used for SARS-CoV-2 Interferon Gamma Release Assay (IGRA). The primary endpoint was to assess the increase of IgG antibody level between baseline and 3 weeks after the booster. Results: One hundred and forty-two consecutive patients were recruited. In SARS-CoV-2-naïve subjects, the median level of IgG was 157 BAU/ml [interquartile range (IQR) 62-423 BAU/ml] at T0 and reached a median of 2080 BAU/ml (IQR 2080-2080 BAU/ml) at 3 weeks after booster administration (T1; P < 0.0001). A median 16-fold increase of SARS-CoV-2 NT Ab titer (IQR 4-32) was observed in naïve subjects (from median 20, IQR 10-40, to median 640, IQR 160-640; P < 0.0001). Median interferon-γ level at T1 was significantly higher than that measured at T0 in SARS-CoV-2-naïve subjects (P = 0.0049) but not in SARS-CoV-2-experienced patients. The median level of SARS-CoV-2 NT Abs was 32-fold lower against Omicron compared to the wild-type strain (P = 0.0004) and 12-fold lower compared to the Delta strain (P = 0.0110). Conclusions: The third dose is able to trigger both the humoral and the cell-mediated immune response in cancer patients on active treatment. Our preliminary data about the neutralization of the SARS-CoV-2 vaccine against variants of concern seem to confirm the lower vaccine activity