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Antonio Coviello,1 Alessio Bernasconi,2 Giovanni Balato,2 Ezio Spasari,1 Marilena Ianniello,1 Massimo Mariconda,2 Maria Vargas,1 Carmine Iacovazzo,1 Francesco Smeraglia,2 Andrea Tognù,3 Giuseppe Servillo1 1Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples “Federico II”, Naples, 80100, Italy; 2Department of Public Health, School of Medicine, University of Naples “Federico II”, Unit of Orthopedics and Traumatology, Naples, Italy; 3Department of Anesthesiology and Intensive Care Medicine, Istituto Ortopedico Rizzoli IRCCS, Bologna, 40136, ItalyCorrespondence: Antonio Coviello, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples “Federico II”, Via Vitruvio, 3, Naples, 80100, Italy, Email antonio_coviello@live.itBackground and Aim: Ultrasound-guided continuous adductor canal block (cACB) is a conventional choice in patients undergoing total knee arthroplasty (TKA) for the management of the postoperative pain. This study aims to compare different catheter tip locations for cACB relative to the saphenous nerve (anteriorly vs posteriorly) in terms of efficacy and complications.Methods: At the department of Surgical Sciences, Orthopedic Trauma and Emergencies of the University of Naples Federico II (Naples, Italy), between January 2020 and November 2021, retrospective comparative study was executed. Patients planned for TKA were included in the study if they met the follow inclusion criteria: patients undergone TKA; aged 50– 85 years; body mass index (BMI) of 18– 35 kg/m2; American Society of Anesthesiologists (ASA) physical status classification from I to III; subarachnoid technique for anesthesiology plane; continuous adductor canal block performed by an anesthetist with considerable experience. Patients were assigned to receive cACB with the catheter tip located anteriorly (Group 1, G1) or posteriorly to the saphenous nerve (Group 2, G2). Postoperative pain, ambulation ability, episodes of pump block and rate of catheter dislodgement and leakage were evaluated and analyzed.Results: Altogether, 102 patients were admitted to the study (48 in G1 and 54 in G2). After the first 8 postoperative hours, in G1 17 patients (35.4%) had a VAS greater than 4, while in group 2 only 3 patients (5.6%) had a VAS greater than 4 (p-value < 0.01). All patients of both groups showed ambulation ability in the postoperative period. No episode of leakage was recorded. While the catheter displacement rate was similar in the two groups (2.1% for G1 vs 3.7% for G2; p-value > 0.05), the episodes of pump block were significantly less in G2 than in G1 (3.7% vs 20.8%; p-value < 0.01).Conclusion: In cACB for TKA, we found that positioning the catheter tip posteriorly to the saphenous nerve may lead to a greater postoperative analgesia and reduce the risk of pump block compared to placing the catheter tip anteriorly to the nerve.Keywords: continuous adductor canal block, catheter displacement, catheter location, saphenous nerve, total knee arthroplasty

Background: Microsatellite instability (MSI) is a well-established predictive biomarker for immune checkpoint inhibitor (ICI) response in metastatic colon cancer. Both high MSI and tumor mutational burden (TMB) are markers of genomic instability. However, the prognostic and predictive value of TMB in patients with microsatellite stable (MSS) tumors remains unclear., Methods: We evaluated the prognostic significance of TMB levels in MSS metastatic colon cancer patients undergoing standard treatments. Tumor responses were assessed using RECIST v1.1 criteria. Comprehensive clinical and molecular profiling was conducted, including next-generation sequencing (NGS) for TMB evaluation with the TruSight Oncology® kit. Overall survival (OS) was the primary endpoint. Multivariate Cox regression analysis was utilized to assess the relationship among potential prognostic factors., Results: Among 102 MSS metastatic colon cancer patients, high TMB (> 10 mut/mb) was associated with a significantly longer median OS compared to low TMB (70.0 vs 45.0 months, respectively; HR: 0.45; 95% CIs 0.21 to 0.96; P = 0.0396). Multivariate analysis, adjusting for age, gender, number of metastatic sites, response to first-line chemotherapy, RAS mutational status, and liver involvement, identified TMB as an independent prognostic factor, along with response to first-line chemotherapy., Conclusions: Our results highlight the prognostic significance of TMB in MSS metastatic colon cancer patients, suggesting its potential role in patient stratification and treatment decision-making., Competing Interests: Declarations. Ethics approval and consent to participate: In accordance with local and national laws, ethics approval and consent to participate were exempted due to the retrospective/observational and non-interventional nature of the work. However, all patients involved in this study provided written informed consent before undergoing treatment administration and molecular assessments. Consent for publication: Not applicable. Competing interests: Roberto Sirica, Giovanni Savarese, and Monica Ianniello are employed by AMES, Centro Polidiagnostico Strumentale srl, 80013 Naples, Italy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024. The Author(s).)

Glioblastoma (GBM) is a highly aggressive brain cancer with poor clinical outcome. Unfortunately, chemotherapy with temozolomide (TMZ) has a limited efficacy due to resistance mainly attributed to O6-methylguanine methyl transferase (MGMT) activity. Recently, miR-603 and miR-221 have been identified to target MGMT, thus improving the efficacy of temozolomide (TMZ) in the treatment of GBM. Previously, self-assembling nanoparticles (SANPs) have been proposed to deliver miRNAs into the brain. Here, SANP co-encapsulating miRNA-603 (miR-603) and miRNA-221 (miR-221) have been developed to enhance the efficacy of TMZ in the treatment of GBM by preventing the occurrence of chemoresistance. Preliminarily, SANPs encapsulating miRNAs were optimized in terms of lipid composition to assure physical stability and no hemolytic activity. Subsequently, SANPs with the lowest cytotoxicity and excellent internalization efficiency of miRNAs were selected through MTT assay and real-time PCR, respectively. To evaluate a potential synergistic effect between TMZ and miRNAs, MTT and clonogenic assays were performed. In our biological model, miRNA delivery via SANPs in combination with TMZ treatment strongly reduced cell viability and tumorigenic potential. Finally, in vivo assays were carried out on orthotopic xenograft mouse models. The treatment with SANPs encapsulating both miRNAs in combination with TMZ greatly decreased tumour growth, and even more significantly increased animal survival. In conclusion, this strategy provides the rationale for the development of new therapeutic approaches based on SANP technology to deliver miRNAs that play a key role in suppressing tumour., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Background/objective: Balanced reciprocal translocations are structural chromosomal anomalies that involve a mutual exchange of segments between two non-homologous chromosomes with a consequent 50-80% risk of conceiving fetuses with unbalanced chromosomal anomalies. This study describes a 37-year-old woman, at 13 + 5 weeks of gestation, who is a balanced reciprocal translocation 46,XX,t(9;18)(q34;q11.2) carrier, with a high-risk non-invasive prenatal screening test, NIPT, for chromosome 18 aneuploidy., Methods: The highlighted aneuploidy was characterized with cytogenetic, FISH and SNP-array techniques., Results: Cytogenetic analysis, performed on flask-cultured amniocytes, indicated a 48,XX,+2mar karyotype on 50 metaphases. SNP array analysis showed a 15.3 Mb duplication of chromosome 18p (arr[hg19]18p11.32-p11.21(12,842-15,303,932)x4), consistent with a partial tetrasomy 18p, and a 926 kbp duplication of chromosome 9q (arr[GRCh37]9q34.3(140,118,286-141,044,489)x3), consistent with partial trisomy 9q. FISH analysis with a 9q34.3 probe was performed on flask-cultured amniocytes' metaphases, highlighting the presence of a third signal on one of the two marker chromosomes (18p11.32-p11.21)., Conclusions: The evidence of such partial aneuploidies suggests that different mutational events may be possible at meiotic segregation or probably post-meiotic segregation. The results obtained highlight the high sensitivity of the screening test, NIPT, with massive parallel sequencing, and the usefulness of cytogenetics, cytogenomics and molecular biology techniques, in synergy, to characterize and confirm positive NIPT results.

Prostate cancer, a prevalent malignancy affecting the prostate gland, is a significant global health concern. Androgen-deprivation therapy (ADT) has proven effective in controlling advanced disease, with over 50% of patients surviving at the 10-year mark. However, a diverse spectrum of responses exists, and resistance to ADT may emerge over time. This underscores the need to explore innovative treatment strategies for effectively managing prostate cancer progression. Ongoing research endeavors persist in unraveling the complexity of prostate cancer and fostering the development of biologic and innovative approaches, including immunotherapies and targeted therapies. This review aims to provide a valuable synthesis of the dynamic landscape of emerging drug modalities in this context. Interestingly, the complexities posed by prostate cancer not only present a formidable challenge but also serve as a model and an opportunity for translational research and innovative therapies in the field of oncology.

Background: TAS-102 (Lonsurf ® ) is an oral fluoropyrimidine consisting of a combination of trifluridine (a thymidine analog) and tipiracil (a thymidine phosphorylation inhibitor). The drug is effective in metastatic colorectal cancer (mCRC) patients refractory to fluorouracil, irinotecan and oxaliplatin. This study is a real-world analysis, investigating the interplay of genotype/phenotype in relation to TAS-102 sensitivity., Methods: Forty-seven consecutive mCRC patients were treated with TAS-102 at the National Cancer Institute of Naples from March 2019 to March 2021, at a dosage of 35 mg/m 2 , twice a day, in cycles of 28 days (from day 1 to 5 and from day 8 to 12). Clinical-pathological parameters were described. Activity was evaluated with RECIST criteria (v1.1) and toxicity with NCI-CTC (v5.0). Survival was depicted through the Kaplan-Meyer curves. Genetic features of patients were evaluated with Next Generation Sequencing (NGS) through the Illumina NovaSeq 6000 platform and TruSigt™Oncology 500 kit., Results: Median age of patients was 65 years (range: 46-77). Forty-one patients had 2 or more metastatic sites and 38 patients underwent to more than 2 previous lines of therapies. ECOG (Eastern Cooperative Oncology Group) Performance Status (PS) was 2 in 19 patients. The median number of TAS-102 cycles was 4 (range: 2-12). The most frequent toxic event was neutropenia (G3/G4 in 16 patients). There were no severe (> 3) non-haematological toxicities or treatment-related deaths. Twenty-six patients experienced progressive disease (PD), 21 stable disease (SD). Three patients with long-lasting disease control (DC: complete, partial responses or stable disease) shared an FGFR4 (p.Gly388Arg) mutation. Patients experiencing DC had more frequently a low tumour growth rate (P = 0.0306) and an FGFR4 p.G388R variant (P < 0.0001). The FGFR4 Arg388 genotype was associated with better survival (median: 6.4 months) compared to the Gly388 genotype (median: 4 months); the HR was 0.25 (95% CI 0.12- 0.51; P = 0.0001 at Log-Rank test)., Conclusions: This phenotype/genotype investigation suggests that the FGFR4 p.G388R variant may serve as a new marker for identifying patients who are responsive to TAS-102. A mechanistic hypothesis is proposed to interpret these findings., (© 2024. The Author(s).)

Liquid biopsy is a minimally invasive diagnostic tool for identification of tumor-related mutations in circulating cell-free DNA (cfDNA). The aim of this study was to investigate feasibility, sensitivity, and specificity of non-invasive prenatal test (NIPT) for identification of chromosomal abnormalities in cfDNA from a total of 77 consecutive patients with non-Hodgkin B-cell lymphomas, Hodgkin lymphoma (HL), or plasma cell dyscrasia. In this case series, half of patients had at least one alteration, more frequently in chromosome 6 (23.1%), chromosome 9 (20.5%), and chromosomes 3 and 18 (16.7%), with losses of chromosome 6 and gains of chromosome 7 negatively impacting on overall survival (OS), with a 5-year OS of 26.9% and a median OS of 14.6 months, respectively (P = 0.0009 and P = 0.0004). Moreover, B-cell lymphomas had the highest NIPT positivity, especially those with aggressive lymphomas, while patients with plasma cell dyscrasia with extramedullary disease had a higher NIPT positivity compared to conventional cytogenetics analysis and a worse outcome. Therefore, we proposed a NIPT-based liquid biopsy a complementary minimally invasive tool for chromosomal abnormality detection in hematological malignancies. However, prospective studies on larger cohorts are needed to validate clinical utility of NIPT-based liquid biopsy in routinely clinical practice., (© 2024. The Author(s).)

Oligo-metastatic disease (OMD) in the field of oncology denotes a distinct subset of metastatic tumors characterized by less aggressive biological behavior and extended survival times in comparison to their widely metastatic counterparts. While there is a general consensus regarding the existence of OMD, there remains a lack of widely accepted criteria for its a priori identification at the time of presentation. This review delves into the concept of OMD, placing a particular emphasis on the significance of understanding the limitations and potential of genetic assessments. It explores how these aspects are crucial in advancing our comprehension of this phenomenon. In a rapidly advancing era of precision medicine, understanding the intricacies of OMD opens up exciting possibilities for tailored treatment approaches. By elucidating the genetic underpinnings and dynamic nature of this condition, we stand to improve patient outcomes and potentially shift the paradigm of metastatic cancer management.

In current practice, single-shot spinal anesthesia has traditionally been performed using the conventional surface-anatomic-Landmark-Guided technique. This "blind" technique has significant critical issues such as a high risk of complications due to the numerous attempts at spinal needle placement and the negative impact on the learning curve of the trainees. Ultrasound-Assisted spinal anesthesia could reduce these critical issues and allow trainees to perform the procedure more easily and with fewer complications for the patient. We performed a before-and-after monocentric retrospective comparative study at the University of Naples "Federico II" (Naples, Italy). Inclusion criteria were as follows: patients aged 18 years or older; ASA physical status between I and IV; and elective orthopedic surgery under single-shot spinal anesthesia performed by supervised trainees between January 2022 and December 2022. In the selected cohort, 88 patients were included in group A (Landmark-Guided spinal anesthesia) and 91 in group B (Ultrasound-Assisted spinal anesthesia). The number of attempts by trainees ( p -value < 0.005), procedure performing time (<0.001), and patient discomfort (<0.001) were significantly lower in group B than in group A. Ultrasound-Assisted single-shot spinal anesthesia performed by novice trainees reduces the number of attempts, complication rate, periprocedural pain, and patient discomfort.

Competing Interests: Declaration of Competing Interest L.C., M.I., Marika Casillo, N.P., R.S., R.R., and G.S. are stably employed by AMES, Centro Polidiagnostico Strumentale srl, Naples, Italy. O.G. is Staff Personnel (I3SNS Stable Researcher) of Xunta de Galicia (Servizo Galego de Saude -SERGAS-) through a research-staff contract (ISCIII)/SERGAS). O.G. also declares to be a member of RICORS Programme, RD21/0002/0025 via ISCIII and FEDER. O.G. receives grants for PI20/00902 funded by ISCIII and FEDER. O.G. is member of the COST Action CA21110 Building an open European network on osteoarthritis research (NetwOArk) funded by Eurpean Union under the European Cooperation in Science and technology Programme (COST). O.G. is beneficiary of a grant funded by Xunta de Galicia, Consellería de Educación, Universidade e Formación Profesional and Consellería de Economía, Emprego e Industria (GAIN) (GPC IN607B2022/03). A.O. declares travel, accommodations, expenses supported by Servier, and Astra Zeneca. A.O. declares expenses by Amgen and Servier. A.O. declares honoraria by Amgen, Bayer, Servier. A.O. received unconditional support for ESR-2121257 no-profit project by AstraZeneca. All these activities were unrelated and were performed outside of the submitted work. The other Authors do not have conflict of interests to declare related to the present work.

Cancer manifests as a multifaceted disease, characterized by aberrant cellular proliferation, survival, migration, and invasion. Tumors exhibit variances across diverse dimensions, encompassing genetic, epigenetic, and transcriptional realms. This heterogeneity poses significant challenges in prognosis and treatment, affording tumors advantages through an increased propensity to accumulate mutations linked to immune system evasion and drug resistance. In this review, we offer insights into tumor heterogeneity as a crucial characteristic of cancer, exploring the difficulties associated with measuring and quantifying such heterogeneity from clinical and biological perspectives. By emphasizing the critical nature of understanding tumor heterogeneity, this work contributes to raising awareness about the importance of developing effective cancer therapies that target this distinct and elusive trait of cancer.

Background: The use of robotic surgery is attracting ever-growing interest for its potential advantages such as small incisions, fine movements, and magnification of the operating field. Only a few randomized controlled trials (RCTs) have explored the differences in perioperative outcomes between the two approaches., Methods: We screened the main online databases from inception to May 2023. We included studies in English enrolling adult patients undergoing elective gastrointestinal surgery. We used the following exclusion criteria: surgery with the involvement of thoracic esophagus, and patients affected by severe heart, pulmonary and end-stage renal disease. We compared intra- and post-operative complications, length of hospitalization, and costs between laparoscopic and robotic approaches., Results: A total of 18 RCTs were included. We found no differences in the rate of anastomotic leakage, cardiovascular complications, estimated blood loss, readmission, deep vein thrombosis, length of hospitalization, mortality, and post-operative pain between robotic and laparoscopic surgery; post-operative pneumonia was less frequent in the robotic approach. The conversion to open surgery was less frequent in the robotic approach, which was characterized by shorter time to first flatus but higher operative time and costs., Conclusions: The robotic gastrointestinal surgery has some advantages compared to the laparoscopic technique such as lower conversion rate, faster recovery of bowel movement, but it has higher economic costs.

KRAS is frequently mutated in tumors. It is mutated in approximately 30% of all cancer cases and in nearly 50% of cases of metastatic colorectal cancer (CRC), which is the third leading cause of cancer-related deaths worldwide. Recent advancements in understanding CRC biology and genetics have highlighted the significance of KRAS mutations in the progression of CRC. The KRAS gene encodes a small GTPase (Guanosine TriPhosphatases) that plays a key role in signaling pathways associated with important proteins involved in amplifying growth factor and receptor signals. Mutations in KRAS are frequently observed in codons 12 and 13, and these mutations have oncogenic properties. Abnormal activation of KRAS proteins strongly stimulates signals associated with various cancer-related processes in CRC, including cell proliferation, migration and neoangiogenesis. In this review, we explore the distinct prognostic implications of KRAS mutations. Specifically, the KRAS p.G12C mutation is associated with a worse prognosis in metastatic CRC. The correlation between structure, conformation and mutations is visually presented to emphasize how alterations in individual amino acids at the same position in a single protein can unexpectedly exhibit complex involvement in cancer. Last, KRAS p.G12C is discussed as an emerging and promising therapeutic target in metastatic CRC, providing a concise overview of available clinical data regarding the use of new inhibitors.

Introduction: P53 is one of the most frequently mutated genes in colorectal cancer (CRC). The present study was undertaken to provide a solid estimate of the prognostic value of p53 mutations in metastatic CRC patients., Methods: This meta-analysis was done in accordance to the Preferred Reporting Item For Systematic Reviews and Meta-Analysis 2020 guidelines. Studies in English published in the last ten years were searched through PubMed and Google Scholar. Final selection criteria were: 1) association with overall survival, 2) presence of Hazard Ratios (HRs) with 95% Confidence Intervals (CIs). The articles were evaluated for quality and risk of bias using the Newcastle-Ottawa Scale and QUIPS tool, respectively. The meta-analysis was conducted with random-effects model according to the Hartung-Knapp-Sidik-Jonkman method and results were depicted in classical Forest plots. Studies heterogeneity was determined by I 2 and Tau 2 statistics. The relationship between p53 mutation and clinic-pathological variables was examined using the χ 2 test., Results: Nine articles met the eligibility criteria and went to the final analysis. Sample size ranged from 51 to 1043 patients. All studies were retrospective. The Newcastle Ottawa Scale score was > 6 in all studies, QUIPS risk of bias was low in 6, moderate in 3 studies. Only three studies analysed the entire p53 gene coding region. The DNA sequencing technological platforms varied from Sanger to NGS sequencing techniques. The p53 mutational frequencies ranged from 35.0 % to 73.0 %. A strong association (p < 0.0001) emerged between p53 alteration and left-sided CRC. The final pooled HR (p53 mutated vs p53 wild-type tumors) for overall survival was 1.30 (95 % CI: 0.75-2.25) at random-effects model., Conclusions: The available evidence does not support a prognostic role for p53 in metastatic CRC patients. Prospective studies, with larger sample sizes and consistent and harmonized methodology, are needed to explore the prognostic role of p53 in metastatic CRC patients., Competing Interests: Declaration of Competing Interest G.S., M.I., Marika Casillo, and N.P. are stably employed by AMES, Centro Polidiagnostico Strumentale srl, Naples, Italy. O.G. is Staff Personnel (I3SNS Stable Researcher) of Xunta de Galicia (Servizo Galego de Saude -SERGAS-) through a research-staff contract (ISCIII)/SERGAS). O.G. also declares to be a member of RICORS Program, RD21/0002/0025 via ISCIII and FEDER. O.G. receives grants for PI20/00902 funded by ISCIII and FEDER. O.G. is member of the COST Action CA21110 Building an open European network on osteoarthritis research (NetwOArk) funded by Eurpean Union under the European Cooperation in Science and technology Program (COST). O.G. is beneficiary of a grant funded by Xunta de Galicia, Consellería de Educación, Universidade e Formación Profesional and Consellería de Economía, Emprego e Industria (GAIN) (GPC IN607B2022/03). A.O. declares travel, accommodations, expenses supported by Servier, and Astra Zeneca. A.O. declares expenses by Amgen and Servier. A.O. declares honoraria by Amgen, Bayer, Servier. A.O. received unconditional support for ESR-2121257 no-profit project by AstraZeneca. All these activities were unrelated and were performed outside of the submitted work. The other Authors do not have conflict of interests to declare related to the present work., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Non-invasive prenatal screening (NIPS) in twin gestations has been shown to have high detection rates and low false-positive rates for trisomy 21, as seen in singleton pregnancies, although there have been few large cohort twin studies, genome-wide studies in particular, to date. In this study, we looked at the performance of genome-wide NIPT in a large cohort consisting of 1244 twin pregnancy samples collected over a two-year period in a single laboratory in Italy. All samples underwent an NIPS for common trisomies, with 61.5% of study participants choosing to undergo genome-wide NIPS for additional fetal anomalies (namely, rare autosomal aneuploidies and CNVs). There were nine initial no-call results, all of which were resolved upon retest. Based on our NIPS results, 17 samples were at high risk for trisomy 21, one for trisomy 18, six for a rare autosomal aneuploidy, and four for a CNV. Clinical follow-up was available for 27 out of 29 high-risk cases; a sensitivity of 100%, a specificity of 99.9%, and a PPV of 94.4% were noted for trisomy 21. Clinical follow-up was also available for 1110 (96.6%) of the low-risk cases, all of which were true negatives. In conclusion, we found that NIPS was a reliable screening approach for trisomy 21 in twin pregnancies.

Introduction: We studied the predictive and prognostic influences of hypertension (HT), type 2 diabetes (T2D), weight, and p53 mutations in metastatic colorectal cancer (CRC) patients., Patients and Methods: T2D was diagnosed according to the ADA criteria. HT was classified according to the ACC/AHA guidelines. BMI (body-mass index) was calculated and classified according to the WHO criteria. TruSigt™Oncology 500 kit was applied to construct the genomic libraries for Next Generation Sequencing (NGS) analysis. The Illumina NovaSeq 6000 technological platform and the Illumina TruSight Oncology 500 bioinformatics pipeline were applied to analyze results. Overall survival (OS) was calculated through Kaplan-Meier curves. Univariate and multivariate analyses were performed to assess the relationships between clinical and/or molecular covariates. Associations between HT, T2D, BMI, p53, and clinical variables were evaluated by the χ2 test. P < 0.05 were considered statistically significant., Results: Two-hundred-forty-four patients were enrolled. One-hundred-twenty (49.2%), 110 (45.1%), and 50 (20.5%) patients were affected by overweight, HT, and T2D, respectively. DC (disease control) was achieved more frequently in patients without T2D (83.1%) compared to the diabetic ones (16.9%) ( P = 0.0246). DC, KRAS mutational status, T2D, BMI, and concomitant presence of T2D, BMI, and HT associated with survival ( P < 0.05). At multivariate analysis, age (≥65 vs. <65 years), response to first-line chemotherapy (DC vs. no DC), and concomitant presence of T2D, BMI, and HT (HR: 4.56; 95% CI: 2.40-8.67; P = 0.0217) emerged as independent prognostic variables. P53 was mutated in 31/53 analyzed cases (60.4%). The most frequent gene variants were p.Arg175His and p.Cys135Tyr. High BMI (>25 kg/m 2 ) associated with occurrence of p53 mutations ( P < 0.0001). P53 mutated patients presented a worse prognosis compared to the wild-type ones (HR: 3.21; 95% CI: 1.43-7.23; P = 0.0047)., Conclusion: Diabetic, hypertensive and overweight metastatic CRC patients are a negative prognostic subgroup deserving specific therapeutic strategies. P53 mutations associate with prognosis and BMI unrevealing complex and unexplored connections between metabolism and cancer occurrence., Competing Interests: LC, GS, MI, MCasi, and NP are employed by AMES, Centro Polidiagnostico Strumentale srl, Naples, Italy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ottaiano, Santorsola, Circelli, Perri, Cascella, Sabbatino, Capuozzo, Granata, Zappavigna, Lombardi, Scrima, Petrillo, Ianniello, Casillo, Gualillo, Nasti, Caraglia and Savarese.)

Background: In recent years, the relationship between the advantages and disadvantages of a deep neuromuscular block (DNMB), compared to a moderate block (MNMB) in laparoscopic surgery, has been increasingly studied., Objective: Evaluate the effect of D-NMB compared to M-NMB in gynecological laparoscopic surgery., Methods: This was a parallel-group, double-blind, randomized clinical trial, conducted at a single center in Italy between February 2020 and July 2020. American Society of Anesthesiologist (ASA) I-II risk class patients scheduled for elective gynecological laparoscopic surgery were randomized into a 1:1 ratio to either experimental or control group. The first one included DNMB with a rocuronium bolus at the starting dose of 1.2 mg/kg and a maintenance dose (0.3-0.6 mg/kg/h). The second one included MNMB with a rocuronium bolus at the starting dose of 0.6 mg/kg, and a maintenance dose in boluses (0.15-0.25 mg/kg). The primary outcome was the intraoperative surgical condition assessed every 15 min by the surgeon as a 5-point scale. The secondary outcome was the time needed to discharge patients from post-anesthesia care unit (PACU). The tertiary outcome was the assessment of the intra-operative hemodynamic instability. A sample size of 50 patients was planned., Results: One hundred five patients were assessed for eligibility, 55 were excluded. Fifty patients met the inclusion criteria and were enrolled. The average score for the operative field was 4 for the D-NMB group and 3 for the M-NMB group (p value < 0.01). The length of stay in PACU was 13 min for the DNMB group and 22 min for the MNMB group (p value = 0.02)., Conclusions: Deep neuromuscular block improves intraoperative surgical condition during gynecological laparoscopic surgery., Trial Registration: clinicalTrials.gov NCT03441828., (© 2023. The Author(s).)

Spinal anesthesia is the best choice for caesarean delivery. This technique is characterized by a complete and predictable nerve block with a fast onset and few complications. Several intrathecal adjuvants are used in order to improve the quality and duration of anesthesia and reduce its side effects. Sixty-two patients who underwent caesarean delivery under spinal anesthesia were included in this medical records review. In this retrospective study, after adopting exclusion criteria, we assessed 24 patients who received Hyperbaric Bupivacaine 0.5% 10 mg and dexmedetomidine 10 μg (G1), and 28 patients who received an institutional standard treatment with Hyperbaric Bupivacaine 0.5% 10 mg and sufentanil 5 μg (G2). We evaluated the difference in terms of motor and sensory block, postoperative pain, and adverse effects during the first 24 h following delivery and neonatal outcome. Our study found that the sufentanil group had a significantly lower requirement for analgesia than the dexmedetomidine group. Postoperative pain, assessed with the VAS scale, was stronger in G1 than in G2 (4 ± 2 vs. 2 ± 1, p-value < 0.01). Differences between the two groups regarding the intraoperative degree of motor and sensory block, motor recovery time, and neonatal Apgar scores were not noticed. Pruritus and shivering were observed only in G2. Itching and shivering did not occur in the dexmedetomidine group. Postoperative analgesia was superior in the sufentanil group, but the incidence of side effects was higher. Adjuvant dexmedetomidine prevented postoperative shivering.

Background: We previously reported rare regressive genetic trajectories of KRAS pathogenic mutations as a specific hallmark of the genuine oligometastatic status in colorectal cancer (CRC)., Methods: Survival and prognostic impact of disease extent in 140 metastatic CRC patients were evaluated through the Kaplan-Meyer curves and the Log-Rank test. KRAS mutations were assessed through the Illumina NovaSeq 6000 platform and TruSight™ Oncology 500 kit. HLA typing was carried out by PCR with sequence-specific oligonucleotides. Lymphocyte densities in tumors were expressed as cells per square millimeter. NKs isolated and CD8 + from NK-depleted PBMCs were characterized through flow cytometry. CD107a externalization was evaluated as NKs/CD8 cytotoxicity toward human colon cancer cells HT29, SW620, HCT116, and LS174T carrying different KRAS mutations., Results: The oligometastatic status was a strong and independent variable for survival (HR: 0.08 vs. polymetastatic disease; 95% CI: 0.02-0.26; p  < 0.001). Eighteen oligometastatic patients were selected. Twelve were alive at the last follow-up, and 9 were characterized. Genetic regression of KRAS was observed in 3 patients: patient (PAT)2, PAT5, and PAT8. PAT2 and PAT5 presented the highest levels of GrzB + lymphocytes in the tumor cores of the metastases (120 ± 11.2 and 132 ± 12.2 cells/mm 2 , respectively). Six out of 9 patients (67%), including PAT2 and PAT5, expressed HLA-C7. Twopatients (PAT2 and PAT5) presented high CD3 + /CD8 + -dependent cytotoxicity against HLA-C7+ SW620 cells (p.G12V-mutated cells), which was consistent with their observed mutational regression (p.G12V/p.G13D in primary→p.G13D in metastatic tumor)., Conclusions: We provide evidence that CD3 + /CD8 + lymphocytes from oligometastatic CRC patients display differential cytotoxicity against human colon cancer cells carrying KRAS mutations. This could provide an interesting basis for monitoring oligometastatic disease and developing future adoptive immunotherapies., Competing Interests: GSa, MI, MaC, and NP are employed by AMES, Centro Polidiagnostico Strumentale srl, Naples, Italy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ottaiano, de Vera d’Aragona, Trotta, Santorsola, Napolitano, Scognamiglio, Tatangelo, Grieco, Zappavigna, Granata, Perri, Luce, Savarese, Ianniello, Casillo, Petrillo, Belli, Izzo, Nasti, Caraglia and Scala.)

Surveillance of Echinococcus multilocularis at the edge of its range is hindered by fragmented distributional patterns and low prevalence in definitive hosts. Thus, tests with adequate levels of sensitivity are especially important for discriminating between infected and non-infected areas. In this study we reassessed the prevalence of E. multilocularis at the southern border of its distribution in Province of Bolzano (Alto Adige, northeastern Alps, Italy), to improve surveillance in wildlife and provide more accurate estimates of exposure risk. We compared the diagnostic test currently implemented for surveillance based on coproscopy and multiplex PCR (CMPCR) to a real-time quantitative PCR (qPCR) in 235 fox faeces collected in 2019 and 2020. The performances of the two tests were estimated using a scraping technique (SFCT) applied to the small intestines of a subsample (n = 123) of the same foxes as the reference standard. True prevalence was calculated and the sample size required by each faecal test for the detection of the parasite was then estimated. True prevalence of E. multilocularis in foxes (14.3%) was markedly higher than reported in the last decade, which was never more than 5% from 2012 to 2018 in the same area. In addition, qPCR showed a much higher sensitivity (83%) compared to CMPCR (21%) and agreement with the reference standard was far higher for qPCR (0.816) than CMPCR (0.298) meaning that for the latter protocol, a smaller sample size would be required to detect the disease. Alto Adige should be considered a highly endemic area. Routine surveillance on definitive hosts at the edges of the E. multilocularis distribution should be applied to smaller geographic areas, and rapid, sensitive diagnostic tools using directly host faeces, such as qPCR, should be adopted., Competing Interests: The authors have declared that no competing interests exist.

Background: Our hospital became a referral center for COVID-19-positive obstetric patients from 1 May 2020. The aim of our study is to illustrate our management protocols for COVID-19-positive obstetric patients, to maintain safety standards for patients and healthcare workers., Methods: Women who underwent vaginal or operative delivery and induced or spontaneous abortion with a SARS-CoV-2-positive nasopharyngeal swab using real-time PCR (RT-PCR) were included in the study. Severity and onset of new symptoms were carefully monitored in the postoperative period. All the healthcare workers received a nasopharyngeal swab for SARS-CoV-2 using RT-PCR serially every five days., Results: We included 152 parturients with COVID-19 infection. None of the included women had general anesthesia, an increase of severe symptoms or onset of new symptoms. The RT-PCR test was "negative" for the healthcare workers., Conclusions: In our study, neuraxial anesthesia for parturients' management with SARS-CoV-2 infection has been proven to be safe for patients and healthcare workers. Neuraxial anesthesia decreases aerosolization during preoxygenation, face-mask ventilation, endotracheal intubation, oral or tracheal suctioning and extubation. This anesthesia management protocol can be generalizable.

The most frequent form of colorectal cancer is represented by adenocarcinoma being about 98% of tumor histological types. However, other rare histotypes can be found in colon and rectum (adenosquamous, goblet cell adenocarcinoma, lymphoma, medullary carcinoma, melanoma, mesenchymal, neuroendocrine, plasmacytoma, signet ring, squamous tumors). Altogether, these forms account for less than 2% of colorectal tumors. There are no specific diagnostic or therapeutic recommended approaches and most of the information available from literature derives from small and retrospective clinical series. In the present study, we provide a paramount and updated view on clinical and biologic characteristics of rare colorectal tumors.