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Pulsed current has proven to be a promising alternative to direct current in electrochemical deposition, offering numerous advantages regarding deposit quality and properties. Concerning the electrodeposition of metal alloys, the role of pulsed current techniques may vary depending on the specific metals involved. We studied an innovative tin-ruthenium electroplating bath used as an anti-corrosive layer for decorative applications. The bath represents a more environmentally and economically viable alternative to nickel and palladium formulations. The samples obtained using both direct and pulsed currents were analyzed using various techniques to observe any differences in thickness, color, composition, and morphology of the deposits depending on the pulsed current waveform used for deposition.

Introduction: Pseudomyxoma peritonei (PMP) is a rare, slow growing tumor, traditionally considered chemoresistant. The only curative approach is cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). At disease relapse, or in patients with inoperable disease at diagnosis, no standard treatment has been defined, though nonrandomized series showed promising results with fluoropyrimidine-based regimens., Patients and Methods: We conducted a prospective study in patients with relapsed or unresectable PMP and confirmed disease progression at baseline. Patients received MMC (7 mg/m 2 every 6 weeks, up to a maximum of 4 cycles) plus metronomic capecitabine (625 mg/sqm/day b.i.d.) and bevacizumab (7.5 mg/kg every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), overall response rate according to RECIST v1.1 criteria, serum markers response and safety., Results: Fifteen patients were included. At a median follow-up of 26.1 months (IQR, 17.7-49.6), median PFS was 17.9 months (95% CI, 11.0-NE), with 1-year PFS and OS rates of 73% and 87%. Safety profile was manageable, with only 13% G3/G4 treatment-related adverse events., Conclusion: Metronomic capecitabine, bevacizumab, and MMC are an active regimen in advanced and progressive PMP and favorably compares with historical series., Competing Interests: Disclosure F.P. received honoraria from Amgen, Bayer, Servier, Merck-Serono, MSD, BMS, Takeda, Astellas, Pierre-Fabre and received research grants for academic studies from Bristol-Myers Squibb, AstraZeneca, Agenus, Incyte, Amgen., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Immune checkpoint inhibitors (ICIs) are the standard treatment in patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). Tumour mutational burden (TMB) is a promising biomarker for the prediction of treatment outcomes., Patients and Methods: We screened 203 patients with dMMR/MSI-H mCRC treated with an anti-PD-(L)1 (anti-Programmed-Death-(Ligand)1) plus or minus an anti-Cytotoxic T-Lymphocyte Antigen 4 (anti-CTLA-4) agent at three Italian Academic Centers. TMB was tested by Foundation One Next Generation Sequencing assay and correlated with clinical outcomes, in the overall population and according to ICI regimen., Results: We included 110 patients with dMMR/MSI-H mCRC. Eighty patients received anti-PD-(L)1 monotherapy and 30 received anti-CTLA-4 combinations. Median TMB was 49 mut/Mb (range: 8-251 mut/Mb). The optimal prognostic cut-off for progression-free survival (PFS) stratification was 23 mut/Mb. Patients with TMB ≤23 mut/Mb had significantly worse PFS (adjusted Hazard Ratio [aHR] = 4.26, 95% confidence interval [CI]:1.85-9.82, p = 0.001) and overall survival (OS) (aHR = 5.14, 95% CI: 1.76-14.98, p = 0.003). Using a cut-off optimised for predicting treatment outcome, anti-CTLA-4 combination was associated with a significant PFS/OS benefit versus anti-PD-(L)1 monotherapy in patients with TMB>40 mut/Mb (2-year PFS: 100.0% versus 70.7%, p = 0.002; 2-year OS: 100.0% versus 76.0%, p = 0.025), but not in those with TMB ≤40 mut/Mb (2-year PFS: 59.7% versus 68.6%, p = 0.888; 2-year OS: 80.0% versus 81.0%, p = 0.949)., Conclusion: Patients with dMMR/MSI-H mCRC and relatively lower TMB value displayed early disease progression when receiving ICIs, whereas patients with the highest TMB values may obtain the maximal benefit from intensified anti-CTLA-4/PD-1 combination., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All other authors declared no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Immune checkpoint inhibitors (ICIs) show a tremendous activity in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), but a consistent fraction of patients does not respond. Prognostic/predictive markers are needed. Despite previous investigations in other tumor types, immune-related adverse events (irAEs) have not been well evaluated in patients with MSI-H cancers treated with ICIs., Methods: We conducted an international cohort study at tertiary cancer centers collecting clinic-pathological features from 331 patients with MSI-H mCRC treated with ICIs. Of note, the irAEs were summarized using a 'burden score' constructed in a way that the same score value could be obtained by cumulating many low-grade irAEs or few high-grade irAEs; as a result, the lower the burden the better. Clearly, the irAE burden is not a baseline information, thus it was modeled as a time-dependent variable in univariable and multivariable Cox models., Results: Among 331 patients, irAEs were reported in 144 (43.5%) patients. After a median follow-up time of 29.7 months, patients with higher burden of skin, endocrine and musculoskeletal irAEs (the latter two's effect was confirmed at multivariable analysis) had longer overall survival (OS), as opposed to gastrointestinal, pneumonitis, neurological, liver, renal and other irAEs, which showed an harmful effect. Similar results were observed for progression-free survival (PFS). Based on the results retrieved from organ-specific irAEs, 'aggregated' burden scores were developed to distinguish 'protective' (endocrine and musculoskeletal) and 'harmful' (gastrointestinal, pneumonitis, neurological, hepatic) irAEs showing prognostic effects on OS and PFS., Conclusions: Our results demonstrate that not all irAEs could exert a protective effect on oncologic outcome. An easy-to-use model for ICIs toxicity (burden score of protective and harmful irAEs) may be used as surrogate marker of response., Competing Interests: Competing interests: LS: Speakers’ and consultant’s fees from MSD, Astra-Zeneca, Servier, Bayer, Merck, Amgen, Pierre-FabreMJO: Consulting fees from Pfizer, Merck, Glaxosmithkline, 3D Medicine, Nouscom, Roche. Research fees from Roche, Takeda, Merck, BMS, Astra-Zeneca, Nouscom. FP: Honoraria: Servier, Bayer, AstraZeneca/MedImmune, Lilly, MSD Oncology, Amgen, Pierre-Fabre, Merck-Serono, BMS. Consulting or Advisory Role: Merck-Serono, Amgen, Servier, MSD Oncology, Organon. Research Funding: Bristol Myers Squibb (Inst), AstraZeneca (Inst), Incyte. All other authors declare no specific conflicts of interest(s)., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Prognostic tools to estimate the risk of relapse for patients with liver-limited metastatic colorectal cancer (LL-mCRC) undergoing resection with curative intent are needed. Circulating tumor DNA (ctDNA) as a surrogate of postsurgical minimal residual disease is a promising marker in localized CRC. We explored the role of postoperative ctDNA as a marker of minimal residual disease in patients with radically resected LL-mCRC., Materials and Methods: Seventy-six patients with LL-mCRC were retrospectively included. DNA from tumor tissue was sequenced, and one somatic mutation was then assessed by digital droplet polymerase chain reaction in plasma samples collected after surgery to identify the persistence of ctDNA. Relapse-free survival and postresection overall survival were compared between patients with positive vs negative postoperative ctDNA., Results: ctDNA was found in 39 (51%) of 76 patients with LL-mCRC. At a median follow-up of 77 months, 33 of 39 ctDNA-positive patients and 20 of 37 ctDNA-negative patients experienced disease relapse ( P = .008). ctDNA-positive patients reported significantly shorter RFS than ctDNA-negative ones (median RFS 12.7 v 27.4 months hazard ratio, 2.09, P = .008). In the multivariable model including other prognostic covariates, this association was still significant ( P = .046) and a trend toward shorter overall survival among ctDNA-positive patients was reported (hazard ratio, 1.65, P = .183)., Conclusion: The detection of postsurgical ctDNA is an independent negative prognostic marker and identifies patients at high risk of relapse after liver metastases resection., Competing Interests: Paolo MancaPatents, Royalties, Other Intellectual Property: I have a patent for a method for the identification of gene panels optimal for TMB estimation (Inst) Romano DanesiHonoraria: Lilly, EUSA Pharma, Novartis Italy, Seattle Genetics, GENTILI, AstraZeneca, GlaxoSmithKline Gianluca MasiConsulting or Advisory Role: AstraZeneca, Eisai, MSD OncologyPatents, Royalties, Other Intellectual Property: Terumo (Inst) Marzia Del ReConsulting or Advisory Role: Sanofi, Celgene, Janssen-Cilag, Ipsen, Roche Molecular DiagnosticsSpeakers' Bureau: Sanofi, Pfizer, Novartis, Janssen-Cilag, Ipsen, AstraZeneca, Astellas Pharma, Roche, MSD Oncology Filippo PietrantonioHonoraria: Servier, Bayer, AstraZeneca/MedImmune, Lilly, Sanofi, MSD Oncology, AmgenConsulting or Advisory Role: Amgen, Servier, MSD Oncology, organonResearch Funding: Bristol Myers Squibb (Inst), AstraZeneca (Inst) Chiara CremoliniHonoraria: Roche, Amgen, Bayer, Servier, MSD, Merck, Pierre Fabre, OrganonConsulting or Advisory Role: Roche, Bayer, Amgen, MSD, Pierre Fabre, Nordic PharmaSpeakers' Bureau: Servier, Merck, Pierre FabreResearch Funding: Merck, Bayer, Roche, ServierNo other potential conflicts of interest were reported.

Background: Immune checkpoint inhibitors yielded unprecedented outcomes in patients with mismatch repair deficient/ microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC), but clinical decision-making in this rapidly evolving treatment landscape is challenging. Since performance status (PS) represents a well-established prognostic factor in clinical practice, we investigated whether worse PS, overall or related to either patients' frailty or high tumour burden, could affect the outcomes in this whole patients' population and according to immune checkpoint inhibitor treatment type., Methods: We conducted a global study at Tertiary Cancer Centres and collected data of patients with dMMR/MSI-H mCRC treated with anti- programmed-death (ligand)-1 (PD(L)-1) monotherapy or anti-PD-1/anti- cytotoxic T-lymphocyte antigen 4 combination., Results: The cohort included 502 patients. At a median follow-up of 31.2 months, worse PFS and OS were reported in patients with patient-related PS ≥ 1 (adjusted-HRs: 1.73, 95%CI: 1.06-2.83, p = 0.004 and 2.06, 95%CI: 1.13-3.74, p = 0.001, respectively) and cancer-related PS ≥ 1 (adjusted-HRs: 1.61, 95%CI: 1.19-2.17, p = 0.004 and 1.87, 95%CI: 1.32-2.66, p = 0.001, respectively). Anti-PD-1/anti- cytotoxic T-lymphocyte antigen 4 combination did not provide significantly better survival compared to anti-PD(L)-1 monotherapy in PS 0 subgroup (PFS HR = 0.62, 95%CI: 0.37-1.02, p = 0.059; OS HR = 0.59, 95%CI: 0.32-1.11, p = 0.100) and in patient-related PS ≥ 1 (PFS HR 0.93, 95%CI: 0.31-2.83, p = 0.899; OS HR 1.22, 95%CI: 0.34-4.37, p = 0.760), but the difference was significant and clinically meaningful in the subgroup with cancer-related PS ≥ 1 (PFS HR = 0.32, 95%CI: 0.19-0.53, p < 0.001; OS HR = 0.26, 95%CI: 0.14-0.48, p < 0.001)., Conclusions: In patients with dMMR/MSI-H mCRC, an extensive evaluation of clinical variables including PS may be implemented in the therapy decision-making., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sara Lonardi received honoraria from Amgen, Merck-Serono, Bayer, Servier, Astrazeneca, MSD, Pierre-Fabre; research grants from Merck-Serono. Michael J Overman reports consulting for Merck Sharp & Dohme Corp, AbbVie, Agilvax, Acrotech Biopharma, and Novartis Pharmaceuticals Corp; and scientific/advisory committee member of Takeda Pharmaceuticals (Japan). Thierry André reports consulting/advisory role and/or honoraria from Amgen, Astellas Pharma, Astra-Zeneca, Bristol-Myers Squibb, Chugai, Clovis, Gritstone Oncology, GlaxoSmithKline, Haliodx, Kaleido Biosciences, Merck & Co., Inc., Pierre Fabre, Roche/Ventana, Sanofi, Seagen, Servier and compensation for travel, accommodation, and expenses from Roche/Genentech, MSD & Co., Inc, and Bristol-Myers Squib. Filippo Pietrantonio received honoraria from Amgen, Merck-Serono, Sanofi, Lilly, Bayer, Servier, Astrazeneca, MSD, Organon; research grants from Astrazeneca and BMS. All the other authors declared no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Despite unprecedented benefit from immune checkpoint inhibitors (ICIs) in patients with mismatch repair deficient (dMMR)/microsatellite instability high (MSI-H) advanced gastrointestinal cancers, a relevant proportion of patients shows primary resistance or short-term disease control. Since malignant effusions represent an immune-suppressed niche, we investigated whether peritoneal involvement with or without ascites is a poor prognostic factor in patients with dMMR/MSI-H metastatic colorectal cancer (mCRC) and gastric cancer (mGC) receiving ICIs., Methods: We conducted a global multicohort study at Tertiary Cancer Centers and collected clinic-pathological data from a cohort of patients with dMMR/MSI-H mCRC treated with anti-PD-(L)1 ±anti-CTLA-4 agents at 12 institutions (developing set). A cohort of patients with dMMR/MSI-high mGC treated with anti-PD-1 agents±chemotherapy at five institutions was used as validating dataset., Results: The mCRC cohort included 502 patients. After a median follow-up of 31.2 months, patients without peritoneal metastases and those with peritoneal metastases and no ascites had similar outcomes (adjusted HR (aHR) 1.15, 95% CI 0.85 to 1.56 for progression-free survival (PFS); aHR 0.96, 95% CI 0.65 to 1.42 for overall survival (OS)), whereas inferior outcomes were observed in patients with peritoneal metastases and ascites (aHR 2.90, 95% CI 1.70 to 4.94; aHR 3.33, 95% CI 1.88 to 5.91) compared with patients without peritoneal involvement. The mGC cohort included 59 patients. After a median follow-up of 17.4 months, inferior PFS and OS were reported in patients with peritoneal metastases and ascites (aHR 3.83, 95% CI 1.68 to 8.72; aHR 3.44, 95% CI 1.39 to 8.53, respectively), but not in patients with only peritoneal metastases (aHR 1.87, 95% CI 0.64 to 5.46; aHR 2.15, 95% CI 0.64 to 7.27) when compared with patients without peritoneal involvement., Conclusions: Patients with dMMR/MSI-H gastrointestinal cancers with peritoneal metastases and ascites should be considered as a peculiar subgroup with highly unfavorable outcomes to current ICI-based therapies. Novel strategies to target the immune-suppressive niche in malignant effusions should be investigated, as well as next-generation ICIs or intraperitoneal approaches., Competing Interests: Competing interests: KS paid consulting or advisory roles for Astellas, Lilly, Bristol-Myers Squibb, Takeda, Pfizer, Ono, MSD, Taiho, Novartis, AbbVie, GlaxoSmithKline, Daiichi Sankyo, Amgen, and Boehringer Ingelheim ; honoraria from Novartis, AbbVie, and Yakult; and research funding from Astellas, Lilly, Ono, Sumoitomo Dainippon, Daiichi Sankyo, Taiho, Chugai, MSD, Medi Science and Eisai. JC reports grants and personal fees from Merck, Amgen, Macrogenics, Ono Pharmaceuticals, Foundation Medicine, Daiichi-Sankyo and Bristol Myers Squibb. AK reports honoraria from Ono Pharmaceutical, Bristol-Myers Squibb, Daiichi-Sankyo, Taiho Pharmaceutical, and Eli Lilly outside the submitted work. CC received honoraria from Amgen, Bayer, Merck, Roche, and Servier; has consulting or advisory role at Amgen, Bayer, MSD, and Roche; was a speakers bureau member at Servier; received research funding from Bayer, Merck, and Servier; and received travel and accommodation expenses from Roche and Servier. MO: consulting for Merck Sharp & Dohme, AbbVie, Agilvax, Acrotech Biopharma, and Novartis Pharmaceuticals Corp; and scientific/ advisory committee member of Takeda Pharmaceuticals (Japan). AK reports honoraria from from Ono Pharmaceutical, Bristol-Myers Squibb, Daiichi-Sankyo, Taiho Pharmaceutical, and Eli Lilly outside the submitted work. FP received honoraria from Amgen, Merck-Serono, Sanofi, Lilly, Bayer, Servier, Astrazeneca; research grants from Astrazeneca and BMS. All the remaining authors declared no conflict of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Nowadays, websites, online journals, and social media give access to an extraordinary amount of medical information. Misleading news are often disseminated generating false expectations, exaggerated anxiety, and confusion; in oncology setting, disinformation is perhaps more deleterious than in other fields, with a considerable impact on single patients as well as on families and, more in general, on Public Health. We aimed to promote a better interaction between the health care and the world of communication., Materials and Methods: A regional technical table was established with the aim of drafting a shared document through the consensus conference method in the RAND/University of California Los Angeles variant, identifying strategies to overcome barriers between communication and health care as well as to propose common criteria for an effective dissemination of medical information., Results: Sixteen articles met the inclusion criteria, from which 72 recommendations were drawn to the communication and health field (40 related to specific issues and 32 transversal to all the specific topics). Following an evaluation of relevance by the panel of experts, it was found that 57 recommendations scored more than 7, 13 between 4 and 6.9, and 2 below 4., Conclusion: This consensus and the drawn up document represent a concrete attempt to find a renewed and strategic alliance between key figures in health care and communication operators. As the American Declaration of Independence, our Declaration of Good Communication has identified high-impact recommendations for the best management of patients, providing simple but fundamental concepts and recommendations about effectiveness especially in oncology setting., Competing Interests: Rossana BerardiConsulting or Advisory Role: Lilly, Boehringer Ingelheim, Amgen, AstraZeneca, Novartis, Roche, GlaxoSmithKline, Eisai, MSD Oncology Massimiliano MarinelliHonoraria: Apoteca FarmacieNo other potential conflicts of interest were reported.

Context: A growing body of reports has documented the ability of anticoagulation management services to help patients receiving warfarin therapy achieve better outcomes compared to the care provided by their personal physicians (ie, usual care)., Objective: To compare clinical outcomes associated with anticoagulation therapy provided by a clinical pharmacy anticoagulation service (CPAS) to usual care., Design: Retrospective, observational cohort study, 6 months in duration., Setting: Large nonprofit, group-model health maintenance organization., Patients: A total of 6,645 patients receiving warfarin therapy were included in the final analyses (intervention group, 3,323 patients; control group, 3,322 patients)., Intervention: Anticoagulation therapy for patients in the intervention group was managed by a centralized, telephonic CPAS. Therapy for patients in the control group was managed in the usual manner by their personal physicians., Main Outcome Measures: The primary outcome was the occurrence of anticoagulation therapy-related complications. A secondary outcome was the proportion of time spent in the target international normalized ratio (INR) range for each patient. Cox proportional hazards regression analyses were used to examine the risk of complications in relation to the study group., Results: Patients in the CPAS were 39% less likely to experience an anticoagulation therapy-related complication than were patients in the control group (hazard ratio, 0.61; 95% confidence interval, 0.42 to 0.88). The number of patients needed to treat to prevent an anticoagulation therapy complication was 52. Additional analyses revealed that improved outcomes associated with CPAS were mediated largely through improved therapeutic INR control. Patients in the CPAS group spent 63.5% of study period days within their target INR range compared to 55.2% in the control group (p < 0.001)., Conclusions: A centralized, telephonic, pharmacist-managed anticoagulation monitoring service reduced the risk of anticoagulation therapy-related complications compared to that with usual care. The cumulative evidence supporting the superior care associated with implementing a pharmacist-managed anticoagulation monitoring service was sufficient to recommend widespread implementation.

Study Objectives: To assess the accuracy of warfarin dosing decisions and the degree of numeric bias between two point-of-care devices using a local reference laboratory's international normalized ratio (INR) as the standard measure, and to determine the relationship between dosing decisions and INR values obtained with the point-of-care devices., Design: Prospective study., Setting: Outpatient anticoagulation clinic., Subjects: Two hundred two patients taking oral warfarin and 10 control subjects., Interventions: For the two point-of-care devices, AvoSure and ProTime, the finger-stick method was used to collect capillary blood samples in each subject. At the same visit, one venous blood sample was collected from each subject for the laboratory analysis., Measurements and Main Results: Dosing agreement was assessed as the proportion of agreement between each device and the laboratory in terms of maintenance dosage adjustments (increase, decrease, or no change). The level of agreement between each device and the laboratory was evaluated by dosing agreement analysis, bias analysis, and concordance coefficient analysis. In the dosing agreement analysis, 78% of INR values from the AvoSure device would have resulted in the same dosing decision as that with the laboratory INR values compared with 66% from the ProTime device (p < 0.001). The mean bias for the ProTime device (0.5 +/- 0.4 INR units) was significantly higher (p = 0.005) than that for the AvoSure device (0.4 +/- 0.5 INR units). The ProTime device overestimated low INR values to a greater extent than did the AvoSure device. Concordance between the laboratory measurement and each device was similar (rho(c) = 0.82 for ProTime, rho(c) = 0.76 for AvoSure)., Conclusions: Assessing dosing decisions yielded distinct, useful clinical information. The AvoSure device is associated with less systematic bias and a higher degree of clinical agreement with our reference laboratory measurement than those of the ProTime device.

The change from the sociology of medicine to the sociology of health comes about in a post-modern social context characterized by a complex and ambiguous situation. This is particularly true in the case of maternity where communication between people of different knowledge is fundamental: the researcher, doctor and female patient tend to lean towards an auto-referential relationship based on an informative communication method (as emerged from a survey on how women patients received information in the cities of Bologna and Urbino). Adopting a relational type communication based on listening, the three subjects can create a common system which, thanks also to the support of modern technology, can help to easily overcome the difficulties encountered.

This study was undertaken in order to evaluate the plasma glucose response to oral glucose tolerance test (OGTT, 100 g) and the HbA1c values in pregnant women at different gestational ages. One-hundred twenty-nine OGTTs have been performed in 75 pregnancies. The results obtained show a decrease in glucose tolerance during pregnancy. Mean HbA1c value was significantly higher in women with gestational diabetes mellitus, but values of subjects with gestational diabetes and normal glucose tolerance overlapped widely. In conclusion, HbA1c is not a sensitive parameter in the diagnosis of gestational diabetes mellitus. Further studies are necessary to evaluate its specificity and prognostic significance.

Renal hemodynamic changes and insulin-resistance are normally observed in pregnancy. This study was aimed at evaluating the presence of microalbuminuria in normotensive pregnant subjects with normal or abnormal glucose tolerance. Nineteen pregnant women have been evaluated by oral glucose tolerance test (OGTT, 100 g) and by urine testing for microalbuminuria at 10 weeks of gestation. Eighteen and 14 women have been reexamined respectively at 24 and 32 weeks of gestation. In the subjects examined there was no correlation between microalbuminuria and abnormal glucose tolerance. Microalbuminuria, however, absent when the subjects were examined at 10 weeks of pregnancy, was present in 36% of women examined at 32 weeks of gestation. In conclusion, probably due to renal hemodynamic changes, microalbuminuria appears frequently in late pregnancy.