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Background: Long bones are commonly affected by musculoskeletal tumors, but they also represent one of the most frequent locations for metastases. The treatment is based on pain management and the prevention or stabilization of pathological fractures by intramedullary nailing. While titanium nails are probably the most used, carbon-fiber-reinforced (CFR) nails have emerged as a new option for oncological patients. The aim of this review is to compare titanium and CFR nails according to current findings. Methods: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards were followed: a total of 1004 articles were identified and 10 were included. Results: Traditionally, titanium implants are highly valued for their optimal biomechanical properties and ease of insertion, facilitated by their radiopacity. However, the use of titanium poses challenges in radiotherapy due to interference with radiation dosage and the creation of ferromagnetic artifacts. Conversely, CFR implants have emerged as a recommended option for intramedullary fixation, due to their biomechanical and structural properties and their benefits during radiotherapy and follow-up monitoring X-ray. Conclusions: CFR nailing represents a promising advancement in the surgical management of oncological patients with long bone metastases. However, further studies are needed to increase surgeons' confidence in their use. [ABSTRACT FROM AUTHOR]

Background: Megaprostheses were first employed in oncological orthopedic surgery, but more recently, additional applications have arisen. These implants are not without any risks and device failure is quite frequent. The most feared complication is undoubtedly the implants' infection; however, the exact incidence is still unknown. This systematic review aims to estimate in the current literature the overall incidence of megaprosthesis infections and to investigate possible risk/protective factors. Methods: We conducted a systematic search for studies published from July 1971 to December 2023 using specific keywords. To be included, studies needed to report either the megaprosthesis anatomical site, and/or whether the megaprosthesis was coated, and/or the surgical indication as oncological or non-oncological reasons. Results: The initial literature search resulted in 1281 studies. We evaluated 10,456 patients and the overall infection rate was 12%. In cancer patients, the infection rate was 22%, while in non-oncological patients, this was 16% (trauma 12%, mechanical failure 17%, prosthetic joint infections 26%). The overall infection rates comparing coated and uncoated implants were 10% and 12.5%, respectively. Conclusions: The number of megaprosthesis implants is increasing considerably. In traumatological patients, the infection rate is lower compared to all the other subgroups, while the infection rate remains higher in the cancer patient group. As these devices become more common, focused studies exploring epidemiological data, clinical outcomes, and long-term complications are needed to address the uncertainties in prevention and management. [ABSTRACT FROM AUTHOR]

Background: Post-radiation fractures are a significant complication of cancer treatment, often being challenging to manage and impacting patients' quality of life. This study systematically reviews the literature on fractures in irradiated bones, focusing on risk factors, treatment modalities, and prevention strategies. Factors increasing fracture risk include exposure to high doses of radiation of at least 50 Gy, female gender, menopausal age, and periosteal stripping. Additionally further risk factors are the size of the original tumor and osteoporosis. Methods: A search of PubMed yielded 541 articles, with 4 were ultimately included in the review. These retrospective studies focused on patients undergoing Combined Limb-Sparing Surgery and Radiation Therapy for soft tissue sarcoma. Results: Results show post-radiation fractures affect approximately 4% of patients, with the femur being the most frequently affected site. Intramedullary nailing emerges as the gold standard treatment, with prosthetic replacement or megaprostheses used in the metaepiphyseal region and as salvage procedures. Non-union and infection remain formidable complications. Conclusions: This study highlights the importance of prophylactic nailing in fracture prevention and the efficacy of free vascularized fibular flaps to achieve bone union during revision surgeries. Limited case availability and patient follow-up hinder comprehensive studies, impacting treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: Periprosthetic joint infection (PJI) is a devastating complication that develops after total joint arthroplasty (TJA), whose incidence is expected to increase over the years. Traditionally, surgical treatment of PJI has been based on algorithms, where early infections are preferably treated with debridement, antibiotics, and implant retention (DAIR) and late infections with two-stage revision surgery. Two-stage revision is considered the "gold standard" for treatment of chronic prosthetic joint infection (PJI) as it enables local delivery of antibiotics, maintenance of limb-length and mobility, and easier reimplantation. Many studies have attempted to identify potential predicting factors for early diagnosis of PJI, but its management remains challenging. In this observational retrospective study, we investigated the potential role of inflammatory blood markers (neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory index (SII), systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI)) as prognostic factors in two-stage exchange arthroplasty for PJI. Methods: A single-center retrospective analysis was conducted, collecting clinical data and laboratory parameters from patients submitted to prosthetic explantation (EP) for chronic PJI. Laboratory parameters (PCR, NLR, MLR, PLR, SIRI, SII, and AISI) were evaluated at the explantation time; at 4, 6, and 8 weeks after surgery; and at reimplantation time. The correlation between laboratory parameters and surgery success was evaluated and defined as infection absence/resolution at the last follow-up. Results: A total of 57 patients with PJI were evaluated (62% males; average age 70 years, SD 12.14). Fifty-three patients with chronic PJI were included. Nine patients underwent DAIR revision surgery and chronic suppressive therapy; two patients died. Nineteen patients completed the two-stage revision process (prosthetic removal, spacer placement, and subsequent replanting). Among them, none showed signs of reinfection or persistence of infection at the last available follow-up. The other twenty-three patients did not replant due to persistent infection: among them, some (the most) underwent spacer retention; others (fewer in number) were submitted to resection arthroplasty and arthrodesis (Girdlestone technique) or chronic suppressive antibiotic therapy; the remaining were, over time, lost to follow-up. Of the patients who concluded the two-stage revision, the ones with high SIRI values (mean 3.08 SD 1.7 and p-value 0.04) and MLR values (mean 0.4 SD 0.2 and p-value 0.02) at the explantation time were associated with a higher probability of infection resolution. Moreover, higher variation in the SIRI and PCR, also defined, respectively, as delta-SIRI (mean −2.3 SD 1.8 and p-value 0.03) and delta-PCR (mean −46 SD 35.7 and p-value 0.03), were associated with favorable outcomes. Conclusions: The results of our study suggest that, in patients with PJI undergoing EP, the SIRI and MLR values and delta-SIRI and delta-PCR values could be predictive of a favorable outcome. The evaluation of these laboratory indices, especially their determination at 4 weeks after removal, could therefore help to determine which patients could be successfully replanted and to identify the best time to replant. More studies analyzing a wider cohort of patients with chronic PJI are needed to validate the promising results of this study. [ABSTRACT FROM AUTHOR]

Simple Summary: CD44 is a crucial factor in colorectal cancer, with specific isoforms demonstrating their significance in the development, progression, metastasis, and resistance to therapy. Given the clinical and pathological impact of CD44, it represents a promising molecular target for cancer therapy. In this review, we aim to highlight the predictive and prognostic significance of CD44 in various cancer types, with a particular focus on colorectal cancer. Moreover, we evaluate current therapeutic interventions that target CD44 or reduce its expression, thereby highlighting its potential as an effective therapeutic strategy. Cluster of differentiation 44 (CD44) is a non-kinase cell surface glycoprotein. It is overexpressed in several cell types, including cancer stem cells (CSCs). Cells overexpressing CD44 exhibit several CSC traits, such as self-renewal, epithelial–mesenchymal transition (EMT) capability, and resistance to chemo- and radiotherapy. The role of CD44 in maintaining stemness and the CSC function in tumor progression is accomplished by binding to its main ligand, hyaluronan (HA). The HA-CD44 complex activates several signaling pathways that lead to cell proliferation, adhesion, migration, and invasion. The CD44 gene regularly undergoes alternative splicing, resulting in the standard (CD44s) and variant (CD44v) isoforms. The different functional roles of CD44s and specific CD44v isoforms still need to be fully understood. The clinicopathological impact of CD44 and its isoforms in promoting tumorigenesis suggests that CD44 could be a molecular target for cancer therapy. Furthermore, the recent association observed between CD44 and KRAS-dependent carcinomas and the potential correlations between CD44 and tumor mutational burden (TMB) and microsatellite instability (MSI) open new research scenarios for developing new strategies in cancer treatment. This review summarises current research regarding the different CD44 isoform structures, their roles, and functions in supporting tumorigenesis and discusses its therapeutic implications. [ABSTRACT FROM AUTHOR]

Simple Summary: In this review, we aim to analyze the molecular bases of angiogenesis in metastatic colorectal cancer (mCRC) and to provide an overview of potential predictive factors for treatment response to anti-angiogenic drugs in mCRC patients. We based our research on literature data focusing on circulating, tissue, and imaging biomarkers that can potentially be used to predict tumour response to anti-angiogenic inhibitors. In this perspective, biological factors and functional imaging seem very promising approaches and further research in these fields will provide clinicians with useful tools to improve patient selection and outcomes. Colorectal cancer (CRC) is a leading tumor worldwide. In CRC, the angiogenic pathway plays a crucial role in cancer development and the process of metastasis. Thus, anti-angiogenic drugs represent a milestone for metastatic CRC (mCRC) treatment and lead to significant improvement of clinical outcomes. Nevertheless, not all patients respond to treatment and some develop resistance. Therefore, the identification of predictive factors able to predict response to angiogenesis pathway blockade is required in order to identify the best candidates to receive these agents. Unfortunately, no predictive biomarkers have been prospectively validated to date. Over the years, research has focused on biologic factors such as genetic polymorphisms, circulating biomarkers, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and microRNA. Moreover, research efforts have evaluated the potential correlation of molecular biomarkers with imaging techniques used for tumor assessment as well as the application of imaging tools in clinical practice. In addition to functional imaging, radiomics, a relatively newer technique, shows real promise in the setting of correlating molecular medicine to radiological phenotypes. [ABSTRACT FROM AUTHOR]

Immunotherapies have revolutionized cancer treatment approaches. Because not all patients respond positively to immune therapeutic agents, it represents a challenge for scientists who strive to understand the mechanisms behind such resistance. In-depth exploration of tumor biology, using novel technologies such as omics science, can help decode the role of the tumor immune microenvironment (TIME) in producing a response to the immune blockade strategies. It can also help to identify biomarkers for patient stratification and personalized treatment. This review aims to explore these new models and highlight their possible pivotal role in changing clinical practice. [ABSTRACT FROM AUTHOR]

Background: Ankle arthroscopy is indicated for both diagnosis and treatment of a large spectrum of common ankle disorders. It has certain advantages over the open procedure; however, it is important to recognize that there are some complications associated with it. Infections after this procedure are quite uncommon, with an overall estimated incidence of 2%. Given the low incidence of infections after ankle arthroscopy, not a great deal of literature on the topic has been published. The present review aims to provide an overview of the incidence, diagnosis, and treatment of infections after ankle arthroscopy. Methods: A systematic review of the literature indexed in the PubMed, MEDLINE, and Cochrane Library databases using search term "ankle arthroscopy infections" was performed in November 2023. No restrictions were applied concerning the date of publication. The Preferred reporting items for systematic reviews and meta-analyses (PRISMA) were followed. Among all surgical operations for the treatment of ankle and foot pathologies, we included articles with a described superficial or deep infection after ankle arthroscopy. Results: The search resulted in 201 studies. Only 21 studies met our inclusion criteria, and they were included in this systematic review. We evaluated 1706 patients who underwent 1720 arthroscopic tibiotalar procedures at an average age of 42 years old. Out of the 1720 procedures, 41 (2%) were complicated by infection. We divided infectious complications into superficial (68%; 28/41) and deep (32%; 13/41) infections. The most common pathogen isolated was Staphylococcus aureus. Arthroscopic arthrodesis was found to be the most affected by deep infections. Conclusions: Infection after ankle arthroscopy is an uncommon complication. Superficial infections were successfully treated with antibiotics, while surgical debridement, arthroscopic drainage, and intravenous antibiotics were necessary in cases of deep infections. Considering the amount of information on pathogens associated with knee and shoulder infections, there is still a lack of literature on pathogens associated with ankle infections, which makes their management difficulty. [ABSTRACT FROM AUTHOR]

Purpose: Treatment of scaphoid fracture sequelae is still an unsolved problem in hand surgery. Custom-made 3D-printed titanium partial and total scaphoid prosthesis and scaphoid interosseous ligament reconstruction (SLIL) are performed in cases of non-union and isolated aseptic necrosis of the proximal scaphoid pole and when it is impossible to save the scaphoid bone, respectively. This study aims to evaluate the clinical, functional and radiographic results after these two prosthesis implantations. Methods: Between January 2019 and July 2020, nine partial and ten total scaphoid prostheses were implanted using custom-made 3D-printed titanium implants. Evaluation criteria included carpal height ratio (CHR), radioscaphoid angle, wrist extension and flexion, radial deviation and ulnar deviation of the wrist, grip strength and pinch strength, Visual Analogue Scale (VAS), the Disabilities of Arm, Shoulder, and Hand (DASH) score, and the Patient-Rated Wrist Evaluation (PRWE). Results: Clinical, functional, and radiographic improvements were found in all outcomes analyzed for both patient groups. The VAS pain scale obtained the most remarkable improvement at the one-year follow-up. The results of the DASH scores and the PRWE were good, with a great rate of patient satisfaction at the end of the follow-up. SLIL reconstruction also provided excellent stability and prevented a mid-carpal bone collapse in the short- and medium-term follow-up. Conclusions: A custom-made 3D-printed titanium partial or total scaphoid prosthesis is a viable solution for patients with scaphoid non-union and necrosis or complete scaphoid destruction in whom previous conservative or surgical treatment has failed. [ABSTRACT FROM AUTHOR]

Background and aim: Cancers are one of the most frequent causes of death and disability in humans. Skeletal involvement has a major impact on the quality of life and prognosis of cancer patients. Electrochemotherapy is a palliative and minimally invasive oncologic treatment that was first used to treat subcutaneous nodules for malignant tumors. The aim of our review is to evaluate the results of electrochemotherapy in the treatment of bone metastases. Methods: A systematic review of the literature indexed in the PubMed MEDLINE and Cochrane Library databases using the search key words "electrochemotherapy" AND ("metastasis" OR "metastases") was performed. The Preferred Reporting Items for Systematic Reviews and MetaAnalyses was followed. Inclusion criteria were proven involvement of the appendicular skeleton in metastatic carcinoma or melanoma, through at least one percutaneous electrochemotherapy session on the metastatic bone lesion. The exclusion criterion was no skeletal metastatic involvement. Results: Eight articles were finally included. We reached a population of 246 patients. The mean age and follow up were 60.1 years old and 11.4 months, respectively. The most represented primary tumor was breast cancer (18.9%). A total of 250 bone lesions were treated with electrochemotherapy. According to RECIST criteria, in our population we observed 55.5% stable diseases. The mean pre-electrochemotherapy VAS value was 6.9, which lowered to 2.7 after treatment. Adverse events occurred in 3.4% of patients. Conclusions: Electrochemotherapy as a minimally invasive and tissue-sparing treatment should be considered for patients with no other alternative to obtain tumor control and improvement in quality of life. [ABSTRACT FROM AUTHOR]

(1) Background: Some of the goals of orthopedic surgical oncology are saving limbs and function. The humerus is the third most frequent site in primary tumors and one of the most involved sites for metastases. Prosthetic replacement with modular megaprosthesis is one of the treatment choices, but there are several types of complications, such as problems with function and pain. The aim of our study is to assess functional outcomes and shoulder instability in the reconstruction of proximal humerus metastases. (2) Methods: This is a retrospective observational study. Twenty-eight patients, with proximal humerus metastases, admitted to the department of Orthopaedics and Traumatology of our University Hospital between 2014 and 2022 were recruited. Each patient underwent resection and prosthetic replacement surgery with modular megaprosthesis. Clinical evaluation was assessed through MSTS score, WOSI index, and DASH score. (3) Results: Twenty patients were included in the study. Fairly good results, especially regarding pain, function, and emotional acceptance, were obtained in all three tests: DASH, MSTS, and WOSI. Patients who reported shoulder instability actually have worse outcomes than those who report having stable shoulders. In addition, patients with a resection >10 cm have worse outcomes than those who had a resection of 10 cm. No significant differences were found between the deltopectoral approach group and the lateral approach group. (4) Conclusions: Reconstructive surgery with megaprosthesis of the proximal humerus in patients with metastases can be considered a treatment option, especially in patients with pathological fractures or injuries with a high risk of fracture and good life expectancy. This study shows how this type of surgery affects instability, but in terms of functionality, pain, and patient satisfaction, it gives satisfactory results. [ABSTRACT FROM AUTHOR]

Simple Summary: In our study, we analyzed the role of CD44 expression as a prognostic marker in patients with metastatic colorectal cancer. CD44 is a multi-structural and multifunctional non-kinase transmembrane glycoprotein. Its expression is recognized as a molecular marker of cancer stem cells. Due to its role in the maintenance of stemness and the function of CSCs in tumor progression, CD44 could be an important prognostic marker. In our study, elevated CD44 expression correlated with more aggressive tumor behavior and poor prognostic features, suggesting its role as a novel prognostic marker and potential therapeutic target for mCRC patients. Background: The transmembrane glycoprotein CD44, the major hyaluronan (HA) receptor, has been proven to regulate cell growth, survival, differentiation, and migration. It is therefore widely considered to be involved in carcinogenesis. Its role as a new therapeutic target in solid tumors is under evaluation in clinical trials. The prognostic value remains controversial. Here, we aimed to investigate the correlation between CD44 expression and the clinicopathological features and survival in metastatic colorectal cancer (mCRC) patients. Methods: Data from 65 mCRC patients of the Medical Oncology Unit, University Hospital and University of Cagliari were retrospectively collected from 2008 to 2021. Immunohistochemical analysis was performed at the Pathology Division, University Hospital of Cagliari on 3 μm thick sections obtained from paraffin blocks. The intensity of immunohistochemical staining was subclassified into four groups: score 0 if negative or weak membrane staining in less than 10% of tumor cells; score 1+ if weak membrane staining in at least 10% of tumor cells or moderate membrane staining in less than 10% of tumor cells; score 2+ if moderate membrane staining in at least 10% of tumor cells or intensive membrane staining in less than 10% of tumor cells; score 3+ if intense membrane staining in at least 10% of tumor cells. Based on this score, we distinguished patients into low CD44 expression (score 0, 1+, 2+) and high CD44 expression (score 3+). Statistical analysis was performed with MedCalc (survival distribution: Kaplan–Meier; survival comparison: log-rank test; association between categorical variables: Fisher's exact test). Results: Patients' median age was 66 years (range 49–85). Regarding CD44 expression, score was 0 in 18 patients, 1+ in 15 patients, 2+ in 18 patients, and 3+ in 14 patients. Median overall survival (mOS) was 28.1 months (95%CI: 21.3–101). CD44 overexpression (3+) was correlated with poor prognosis (p = 0.0011; HR = 0.2), with a mOS of 14.5 months (95%CI 11.7 to 35.9) versus 30.7 months (95%CI 27.8 to 101) in lower CD44 expression. Higher CD44 expression was associated with clinically poor prognostic features: age ≥ 70 years (p = 0.0166); inoperable disease (p = 0.0008); stage IV at diagnosis (p = 0.0241); BRAF mutated (p = 0.0111), high-grade tumor (p = 0.0084). Conclusions: CD44 markedly correlated with aggressive tumor behavior and contributed to the earlier progression of disease, thus suggesting its role as a novel prognostic marker and potential therapeutic target for mCRC patients. [ABSTRACT FROM AUTHOR]

Bone can be affected by different neoplastic conditions. Limb salvage surgery has become the preferred treatment strategy for most malignant tumors of the extremities. Advanced 3D printing technology has transformed the conventional view of oncological surgery. These types of implants are produced by electron beam melting (EBM) technology by sintering titanium powder in a scaffold shape designed following a project designed from HRCT and MRI. The aim of our study was to evaluate the outcomes and the mid-term follow-up of a population treated with 3D-printed custom-made prosthesis implantation in major oncological bone resection or after failure of primary implants. The primary outcome was the general patient satisfaction one year after surgery. The secondary outcomes were: mortality rate, treatment related complication rate, functional and clinical outcomes (KPS, ADL and IADL). Eight patients were included, five females and two males, with a mean age of 50.3 (±23.72) years at the surgery. The enrolled patients reported a mean satisfaction rate after surgery of 7.38 (±2) where 10 was the maximum value. There were no changes between pre- and postoperative mean KPS (81.43 +/−10.69). Mean preoperative ADL and IADL score was in both cases 4.86 (±1.07), while postoperative was 5 (±0.82), with a delta of 0.13 (p > 0.05). Custom-made prosthesis permits reconstructing bone defects caused by large tumor resection, especially in anatomically complex areas, restoring articular function. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a major cause of cancer mortality. Early diagnosis is relevant for its prevention and treatment. Since DNA methylation alterations are early events in tumourigenesis and can be detected in cell-free DNA, they represent promising biomarkers for early CRC diagnosis through non-invasive methods. In our previous work, we identified 74 early altered CpG islands (CGIs) associated with genes involved in cell cross-talking and cell signalling pathways. The aim of this work was to test whether methylation-based biomarkers could be detected in non-invasive matrices. Our results confirmed methylation alterations of GRIA4 and VIPR2 in CRC tissues, using MethyLight, as well as in stool samples, using a much more sensitive technique as droplet digital PCR. Furthermore, we analysed expression levels of selected genes whose promoter CGIs were hypermethylated in CRC, detecting downregulation at mRNA and protein levels in CRC tissue for GRIA4, VIPR2, SPOCK1 and SLC6A3. Most of these genes were already lowly expressed in colon normal tissues supporting the idea that cancer DNA methylation targets genes already barely expressed in the matched normal tissues. Our study suggests GRIA4 and VIPR2 as biomarkers for early CRC diagnosis using stool samples and confirms downregulation of genes hypermethylated in CRC. [ABSTRACT FROM AUTHOR]

Background: In the last decade, a series of analyses failed to identify predictive biomarkers of resistance/susceptibility for anti-angiogenic drugs in metastatic colorectal cancer (mCRC). We conducted an exploratory preplanned analysis of serum pro-angiogenic factors (SErum aNgiogenesis-cenTRAL) in 72 mCRC patients enrolled in the phase II CENTRAL (ColorEctalavastiNTRiAlLdh) trial, with the aim to identify potential predictive factors for sensitivity/resistance to first line folinic acid-fluorouracil-irinotecan regimen (FOLFIRI) plus bevacizumab. Methods: First-line FOLFIRI/bevacizumab patients were prospectively assessed for the following circulating pro-angiogenic factors, evaluated with ELISA (enzyme-linked immunosorbent assay)-based technique at baseline and at every cycle: Vascular endothelial growth factor A (VEGF-A), hepatocyte growth factor (HGF), stromal derived factor-1 (SDF-1), placental derived growth factor (PlGF), fibroblast growth factor-2 (FGF-2), monocyte chemotactic protein-3 (MCP-3), interleukin-8 (IL-8). Results: Changes in circulating FGF-2 levels among different blood samples seemed to correlate with clinical outcome. Patients who experienced an increase in FGF-2 levels at the second cycle of chemotherapy compared to baseline, had a median Progression Free Survival (mPFS) of 12.85 vs. 7.57 months (Hazard Ratio—HR: 0.73, 95% Confidence Interval—CI: 0.43-1.27, p = 0.23). Similar results were seen when comparing FGF-2 concentrations between baseline and eight-week time point (mPFS 12.98 vs. 8.00 months, HR: 0.78, 95% CI: 0.46–1.33, p = 0.35). Conclusions: Our pre-planned, prospective analysis suggests that circulating FGF-2 levels' early increase could be used as a marker to identify patients who are more likely to gain benefit from FOLFIRI/bevacizumab first-line therapy. [ABSTRACT FROM AUTHOR]

Background: Metastatic CRC (mCRC) is a molecular heterogeneous disease. The aim of this review is to give an overview of molecular-driven treatment of mCRC patients. Methods: A review of clinical trials, retrospective studies and case reports was performed regarding molecular biomarkers with therapeutic implications. Results: RAS wild-type status was confirmed as being crucial for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies and for rechallenge strategy. Antiangiogenic therapies improve survival in first- and second-line settings, irrespective of RAS status, while tyrosine kinase inhibitors (TKIs) remain promising in refractory mCRC. Promising results emerged from anti-HER2 drugs trials in HER2-positive mCRC. Target inhibitors were successful for BRAFV600E mutant mCRC patients, while immunotherapy was successful for microsatellite instability-high/defective mismatch repair (MSI-H/dMMR) or DNA polymerase epsilon catalytic subunit (POLE-1) mutant patients. Data are still lacking on NTRK, RET, MGMT, and TGF-β, which require further research. Conclusion: Several molecular biomarkers have been identified for the tailored treatment of mCRC patients and multiple efforts are currently ongoing to increase the therapeutic options. In the era of precision medicine, molecular-biology-driven treatment is the key to impro patient selection and patient outcomes. Further research and large phase III trials are required to ameliorate the therapeutic management of these patients. [ABSTRACT FROM AUTHOR]

Background/Objectives: Periprosthetic joint infection (PJI) is a disastrous complication after joint replacement procedures as the diagnosis remains a significant challenge. The objective of this study is to assess the accuracy and test the interdependency of the proposed compound serum biomarkers for the diagnosis of PJI after total hip arthroplasties (THA). Methods: From January 2019 to December 2023, 77 consecutive cases that underwent revision total hip arthroplasties (rTHA) were included in a single−retrospective, observational cohort study. A total of 32 arthroplasties were classified as having septic complications using the European Bone and Joint Infection Society (EBJIS) definition from 2021, while the other 45 cases were assigned as aseptic failures (AF). Results: In the univariate analysis between the two groups created, statistically significant differences (p < 0.005) were found for the following variables: time from primary arthroplasty to symptom onset (Time PA−SO), neutrophil count, Lymphocyte count, haematocrit level (HCT) and haemoglobin level (HGB), C−reactive protein (CRP), the neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), monocyte lymphocyte ratio (MLR), systemic inflammation index (SII), systemic inflammation response index (SIRI), and aggregate inflammation systemic index (AISI). The ROC curve analysis showed that the SII (sensitivity 90.6% and specificity 62.2%) and the NLR (sensitivity 84.4% and specificity 64.4%) are the most accurate biomarkers. The multivariate analysis confirmed that NLR > 2.63 (p = 0.006), PLR > 147 (p = 0.021), MLR > 0.31 (p = 0.028), SII > 605.31 (p = 0.002), SIRI > 83.34 (p = 0.024), and AISI > 834.86 (p = 0.011) are all closely related to PJI diagnosis independently. Conclusions: The proposed serum biomarkers can be correlated with PJI diagnosis with the reserve of relatively low specificities. [ABSTRACT FROM AUTHOR]

Simple Summary: Primary bone tumors are rare, representing less than 0.2% of all malignancies. However, they constitute a relevant cause of disability due to their impact on the physical function and quality of life of affected patients. Surgical limb salvage is the first approach to bone tumors, whenever possible. The rehabilitative goals are reducing physical impairment and gaining functional independence. These goals must be equally considered to enable patients to become as independent as possible in their daily activities, achieving a sense of normalcy and well-being. This study aims to enhance the clinical practice approaches for patients with bone tumors treated with megaprostheses. Given this objective, we focused on three main outcomes: functional, surgical, and oncological. The optimal management of bone tumors requires a multidisciplinary strategy to guarantee high-quality care. At specialized centers, the medical team responsible for managing patients with bone cancer comprises oncologists, surgeons, radiologists, pathologists, and rehabilitation specialists. The goal of treatment is to achieve long-term survival with minimal disability and pain. Postoperative rehabilitation is a fundamental therapeutic approach to enhance functionality and sustain the utmost quality of life following a limb-sparing surgery. Currently, megaprostheses are used for reconstructing bone defects after tumor resection, but in the literature, only a few studies have investigated rehabilitation outcomes in terms of functionality and impact on daily activities. This narrative review explores the functional and quality of life outcomes after the implantation of MUTARS® prostheses in patients with lower extremity bone tumors. A comprehensive search was conducted on PubMed and Scopus using the following MESH terms: "MUTARS", "Megaprosthesis", "bone", "tumors", "metastasis", "lower limb", "rehabilitation", "outcome", and "quality of life", and 10 studies were included. The most frequent oncological pathology was found to be primitive bone tumors treated with modular prostheses. The outcome measures used were the Henderson et al. classification, Harris Hip Scale, Musculoskeletal Tumor Society score, Visual Analog Scale, Range Of Motion, Karnofsky Performance Scale, and quality of life questionnaire. MUTARS® is a well-established treatment option after bone tumor resection, although it involves extensive and complex post-resection reconstruction that exposes joints and tissues to substantial mechanical stress. Proper rehabilitation after MUTARS® surgery is a fundamental therapeutic step, although there is still insufficient evidence in the literature focusing on functional and rehabilitative outcomes. Therefore, more studies and guidelines are needed to define standardized rehabilitation protocols for clinical practice after orthopedic oncologic surgery. [ABSTRACT FROM AUTHOR]

Background: The therapeutic landscape of unresectable hepatocellular carcinoma (uHCC) continues to evolve. Atezolizumab, an anti-programmed cell death ligand 1 (PD-1) immune checkpoint inhibitor (ICI), in combination with bevacizumab, has substantially improved outcomes. This study aims to evaluate the incidence, risk factors, and outcomes in patients who develop infections while receiving atezolizumab and bevacizumab for uHCC. Methods: Patients who received atezolizumab and bevacizumab for uHCC at a single hospital network were included. Types and rates of infections were reported. Covariates compared among infected and non-infected cohorts included age, sex, race, comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status, immunosuppressive use, chronic infections, number of cycles of ICIs given, antibiotic or antiviral therapies at ICI initiation, and line of therapy (first-line, second-line, greater than second-line). Results: Out of 810 evaluable patients, 34 uHCC patients were treated with atezolizumab plus bevacizumab. The mean ± SD age was 66.29 ± 9.39; 28 (82.35%) were males. There were 17 (50%) patients with reported infection, with bacterial infection occurring in 12 (70.59%) patients and COVID-19 in 4 (23.5%). Of the infected patients, eight (47.06%) had one infection, five (29.41%) had two infections, and two (11.76%) had three or more infections. Infected and non-infected patients received a median of 12 (IQR: 5–17) and 4 (IQR: 3–12) ICI cycles (p = 0.18), respectively. Infections did not negatively impact OS or PFS but resulted in treatment delays and discontinuation in 11 (64.71%) and 7 (41.18%) patients, respectively. At the last follow-up, 19 (55.88%) patients died, 9 (52.94%) in the non-infected group vs. 10 (58.82%) in the infected group (p = 1.0). Conclusions: While a broad array of infections occurred in 50% of the patients in this cohort, it did not negatively impact survival outcomes. However, it did impact morbidity, with more all-cause admissions and treatment delays. [ABSTRACT FROM AUTHOR]

Background: Frailty associated with aging increases the risk of falls, disability, and death. The aim of this study is to explore gender-related disparities in the survival outcomes of pathological femoral fractures in older frail patients, while analyzing potential specific prognostic factors. Methods: This study is a retrospective observational analysis conducted at a single medical center. It enrolled all patients aged 65 and above who were admitted to our emergency department between 2016 and 2020 with a diagnosis of pathological femur fracture requiring surgical intervention. The primary study endpoint was evaluating gender-related differences in survival outcomes. The secondary endpoint involves investigating gender-specific prognostic factors through the analysis of clinical and laboratory parameters. Results: The average Charlson Comorbidity Index (CCI) was slightly lower in men, but the difference was not statistically significant (p = 0.53). The Clinical Frailty Scale (CFS) showed similar results, with men and women 5.23 (SD 1.46), also not significant (p = 0.83). An evaluation comparing patients aged 75 years or younger to those older than 75 years found significant differences in health metrics. The average CCI was higher in the over 75 group compared to the under 75 group, with a p-value of 0.001. Similarly, the CFS average was also greater in the over 75 group than in the under 75 group, with a p-value of 0.0001. Complications were more frequent in patients over 75 and those with lower educational qualifications. The evaluation analyzed cardiac patients compared to a control group, revealing that the average age of cardiac patients was 75.22 years, while the control group was younger at 73.98 years (p = 0.5119). The CCI for cardiac patients averaged 6.53, significantly higher than 4.43 for non-cardiac patients (p = 0.0003). Conclusion: Frailty assessment is therefore essential in patients with pathological fracture of the proximal femur and is an important predictor of both gender differences and hospital complications. Enhancing gender analysis in this field is crucial to gather more robust evidence and deeper comprehension of potential sex- and gender-based disparities. [ABSTRACT FROM AUTHOR]

Cardiogenic shock (CS) is one of the most serious complications of myocardial infarction (MI) with a high mortality rate. The timely and effective prevention and early suppression of this adverse event may influence the prognosis and outcome in patients with MI complicated by CS (MI CS). Despite the use of existing pharmaco-invasive options for maintaining an optimal pumping function of the heart in patients with MI CS, its mortality remains high, prompting the search for new approaches to pathogenetic therapy. This review considers the role of the systemic inflammatory response in the pathogenesis of MI CS. The primary processes involved in its initiation are described, including the progression from the onset of MI to the generalization of the inflammatory response and the development of multiple organ dysfunction. The approaches to anti-inflammatory therapy in patients with CS are discussed, and further promising research directions are outlined. In this review, we updated and summarized information on the inflammatory component of MI CS pathogenesis with a particular focus on its foundational aspects. This will facilitate the identification of specific inflammatory phenotypes and endotypes in MI CS and the development of targeted therapeutic strategies for this MI complication. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a frequent, worldwide tumor described for its huge complexity, including inter-/intra-heterogeneity and tumor microenvironment (TME) variability. Intra-tumor heterogeneity and its connections with metabolic reprogramming and epithelial–mesenchymal transition (EMT) were investigated with explorative shotgun proteomics complemented by a Random Forest (RF) machine-learning approach. Deep and superficial tumor regions and distant-site non-tumor samples from the same patients (n = 16) were analyzed. Among the 2009 proteins analyzed, 91 proteins, including 23 novel potential CRC hallmarks, showed significant quantitative changes. In addition, a 98.4% accurate classification of the three analyzed tissues was obtained by RF using a set of 21 proteins. Subunit E1 of 2-oxoglutarate dehydrogenase (OGDH-E1) was the best classifying factor for the superficial tumor region, while sorting nexin-18 and coatomer-beta protein (beta-COP), implicated in protein trafficking, classified the deep region. Down- and up-regulations of metabolic checkpoints involved different proteins in superficial and deep tumors. Analogously to immune checkpoints affecting the TME, cytoskeleton and extracellular matrix (ECM) dynamics were crucial for EMT. Galectin-3, basigin, S100A9, and fibronectin involved in TME–CRC–ECM crosstalk were found to be differently variated in both tumor regions. Different metabolic strategies appeared to be adopted by the two CRC regions to uncouple the Krebs cycle and cytosolic glucose metabolism, promote lipogenesis, promote amino acid synthesis, down-regulate bioenergetics in mitochondria, and up-regulate oxidative stress. Finally, correlations with the Dukes stage and budding supported the finding of novel potential CRC hallmarks and therapeutic targets. [ABSTRACT FROM AUTHOR]

Simple Summary: The immune microenvironment surrounding a growing tumor is complex and diverse. Understanding this complexity is crucial for predicting prognosis and response to cancer therapy. Various immune cells, signaling molecules, and extracellular matrix components within this microenvironment interact intricately, influencing tumor progression and treatment effectiveness. A deeper understanding of these interactions can lead to better prognostic markers and more effective, personalized therapeutic strategies. Compared to adults, the pediatric tumor immune microenvironment is less studied. Research on different pediatric tumors has shown that regulatory signaling networks between tumors and surrounding immune cells are critical in shifting the balance between pro- and anti-tumor immune responses. Therefore, gaining insights into the tumor immune composition is key to improving the efficacy of various pediatric cancer therapies, particularly immunotherapies that enhance host anti-tumor immunity. The tumor immune microenvironment is pivotal in cancer initiation, advancement, and regulation. Its molecular and cellular composition is critical throughout the disease, as it can influence the balance between suppressive and cytotoxic immune responses within the tumor's vicinity. Studies on the tumor immune microenvironment have enriched our understanding of the intricate interplay between tumors and their immunological surroundings in various human cancers. These studies illuminate the role of significant components of the immune microenvironment, which have not been extensively explored in pediatric tumors before and may influence the responsiveness or resistance to therapeutic agents. Our deepening understanding of the pediatric tumor immune microenvironment is helping to overcome challenges related to the effectiveness of existing therapeutic strategies, including immunotherapies. Although in the early stages, targeted therapies that modulate the tumor immune microenvironment of pediatric solid tumors hold promise for improved outcomes. Focusing on various aspects of tumor immune biology in pediatric patients presents a therapeutic opportunity that could improve treatment outcomes. This review offers a comprehensive examination of recent literature concerning profiling the immune microenvironment in various pediatric tumors. It seeks to condense research findings on characterizing the immune microenvironment in pediatric tumors and its impact on tumor development, metastasis, and response to therapeutic modalities. It covers the immune microenvironment's role in tumor development, interactions with tumor cells, and its impact on the tumor's response to immunotherapy. The review also discusses challenges targeting the immune microenvironment for pediatric cancer therapies. [ABSTRACT FROM AUTHOR]

Bone tumors of the upper limb are a common cause of bone pain and pathological fractures in both old and young populations. Surgical reconstruction and limb salvage have become valid options for these patients despite this kind of surgery being challenging due to the need for wide bone resection and the involvement of surrounding soft tissues. Computer-assisted technology helps the surgeon in pre-operative planning and in designing customized implants. The aim of this study was to investigate the surgical outcomes and complications of custom-made prostheses in oncologic reconstruction of the upper limb and if they are reliable options for patients suffering from aggressive tumors. An electronic search on PubMed, Google Scholar, and Web of Knowledge was conducted to identify all available articles on the use of custom-made prostheses in oncological resections of the upper limb. Twenty-one studies were included in the review, comprising a total of 145 patients with a mean age of 33.68 years. The bone involved was the humerus in 93 patients, and the radius was involved in 36 patients. There were only six cases involving proximal ulna, three cases involving the scapula, and seven cases involving the elbow as well as soft tissues around it. The most frequent primary tumor was the giant cell tumor, with 36 cases, followed by osteosarcoma with 25 cases, Ewing Sarcoma with 17 cases, and Chondrosarcoma with 7 total cases. Forty patients were affected by bone metastases (such as renal cell cancer, breast cancer, melanoma, and rectal cancer) or hematologic diseases involving bone (lymphoma, myeloma, or non-Hodgkin disease). Custom-made prostheses are a viable option for patients who suffer from malignant tumors in their upper limbs. They are a reliable aid for surgeons in cases of extensive resections. [ABSTRACT FROM AUTHOR]

Background: Nowadays, limb-sparing procedures are the gold standard in the treatment of soft-tissue sarcomas of the limbs. Wide tumor resection with appropriate oncological margins, reconstruction, and stabilization of the involved bone and joint and restoration of the soft tissue lost are essential in order to obtain good clinical and functional outcomes. Tumor excision and soft-tissue reconstruction performed in one-step surgery is chosen by many centers as the preferred approach; however, according to our experience in some selected patients, two-step surgery performed using a dermal regeneration template first and then a margin revision, taking into account the definitive results of the anatomopathological exam conducted over the surgical specimen from the previous surgery, associated with definitive reconstruction surgery over a healthy bed of granulated tissue, showed many potential benefits. Methods: A retrospective observational study was conducted on thirteen patients who underwent a two-step reconstruction procedure using dermal substitution after soft-tissue sarcoma excision. Results: Clinically, the enrolled patients achieved excellent contour and cosmesis of their surgical wounds, with a mean VSS value of 3.07. During the follow-up period, no local recurrences were observed in any patient. Conclusions: Two-step surgery represents the most suitable solution to allow surgical radicality with minimal recurrency and adequate soft-tissue reconstruction, avoiding the possibility of wasting autologous tissue. Our patients generally embraced this approach and the management that followed. [ABSTRACT FROM AUTHOR]

Metastatic colorectal cancer requires a multidisciplinary and individualized approach. Herein, we reported the case of a young woman diagnosed with metastatic rectal cancer who received an individualized multimodal treatment strategy that resulted in a remarkable survival. There were several particular aspects of this case, such as the early onset of the disease, the successful use of conversion therapy, the application of liquid biopsy to guide treatment, and the specific nature of the bone metastasis. To offer more insights for navigating such challenges in patients with metastatic colorectal cancer, we have conducted a literature review to find more data related to the particularities of this case. The incidence of early onset colorectal cancer is on the rise. Data suggests that it differs from older-onset colorectal cancer in terms of its pathological, epidemiological, anatomical, metabolic, and biological characteristics. Conversion therapy and surgical intervention provide an opportunity for cure and improve outcomes in metastatic colorectal cancer. It is important to approach each case individually, as every patient with limited liver disease should be considered as a candidate for secondary resection. Moreover, liquid biopsy has an important role in the individualized management of metastatic colorectal cancer patients, as it offers additional information for treatment decisions. [ABSTRACT FROM AUTHOR]

Metastases are complications of primary tumors due to prolonged cancer survival and have become an important issue for oncological patients and the most frequent cause of death and disability. Bone metastases occur at a later stage of cancer disease, and the spine is the most frequent site. To date, the aim of the treatment of metastases remains to be the control of disease and provide a satisfactory quality of life. The decision making of treatment is influenced by several factors such as the status of the primary disease, the number of metastases, site involvement, and the performance status of the patients. For this reason, the treatment of metastases is challenging and undergoes constant development. Therefore, alternative techniques with respect to surgery, which is the first option but not always practicable, and radiochemotherapy are attractive. Lately, electrochemotherapy has emerged as an innovative method for treating various primary and metastatic solid tumors, showing promising outcomes in terms of inducing tumor tissue necrosis and alleviating symptoms. This technique uses electric pulses to increase the uptake of chemotherapy by tumor cells. Despite the initial enthusiasm and good results in the treatment of bone tumors, relatively few papers have described its use in spine metastases. Therefore, we conducted a systemic review of this intriguing topic while also reporting our experience in the use of electrochemotherapy for the treatment of spine metastases. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) stands as a prevalent global health concern, and mineral and bone disease are among the most impactful consequences. A severe complication arising from mineral and bone disease is the occurrence of fragility fractures, which disproportionately affect individuals with CKD compared to the general population. The prevalence of these fractures impacts both survival rates and quality of life. The aims of this study are analyzing and identifying (i) patient-related risk factors and (ii) CKD-related risk factors to contribute to the development of preventive measures for fragility fractures for this population. Methods: A retrospective, single-center observational study was conducted, encompassing patient data from the years 2021 to 2023. Registry data were recorded, including patient-related and CKD-related data. Patients were interviewed about traumatological history, and their answers were recorded. Logistic regression analysis was employed to investigate the association between independent variables and dependent variables. Results: Eighty-four patients, with a mean age of 64.3 ± 15.2 years and a male percentage of 58.3%, were included in this study. Among them, 19.5% exhibited smoking habits. The mean Charlson Comorbidity Index was 3.06 ± 1.21. All patients were diagnosed with end-stage chronic kidney disease, with mean durations of 208 months from the diagnosis and 84.5 months from the beginning of dialysis. The logistic regression analysis, adjusted for age, sex, and CCI, revealed that smoking habits play a significant role as a risk factor for fragility fractures in lower limbs (p: 0.011 *). The incidence of fragility fractures increases directly proportionally to the time since diagnosis (p-value: 0.021 *) and the beginning of dialysis treatment (p-value: 0.001 *). Conclusions: Among patient-related factors, smoking habits seem to significantly affect lower-limb fracture rates (p < 0.05), whereas among CKD-related factors, time since CKD diagnosis and time since the beginning of dialysis treatment are directly related to higher risks of fragility fractures. No relevant correlations emerged in the studied treatments, except for a reduction in proximal femur fracture occurrence when patients underwent a combined treatment of a calcimimetic and a vitamin D analog. [ABSTRACT FROM AUTHOR]

Simple Summary: Circulating tumor cells (CTCs) are cancer cells released from the primary tumor into the bloodstream, and contain cancer stem cells. The present study demonstrates the significance of a specific variant, CD44v9, in CTCs, and its combined effects with preoperative carcinoembryonic antigen (CEA) values on the prognosis of colorectal cancer (CRC). Analysis of the serum CEA levels and the expression of CD44v9 mRNA in CTCs, followed by evaluation of their association with clinicopathological factors, showed the association of CD44v9 mRNA with liver metastasis. Furthermore, patients with CD44v9-positive CTCs showed a poorer prognosis than those with CD44v9-negative CTCs. Combining CD44v9 mRNA expression with CEA values provided more detailed prognostic information. These results suggest that CD44v9 mRNA expression in CTCs, alongside CEA levels, could serve as a valuable prognostic marker for CRC, and could potentially lead to the development of more personalized treatment strategies against CRC. Circulating tumor cells (CTCs) are cancer cells released from the primary tumor into the bloodstream, and contain cancer stem cells that influence tumor survival, recurrence, and metastasis. Here, we investigated CD44v9 expression in CTCs and impact of preoperative carcinoembryonic antigen (CEA) levels on colorectal cancer (CRC) prognosis. We analyzed the expression of CD44v9 mRNA in CTCs using reverse transcription-polymerase chain reaction and preoperative CEA levels in blood samples obtained from 300 patients with CRC. Subsequently, we evaluated the association of CD44v9 expression and CEA levels with clinicopathological factors. CD44v9 mRNA was expressed in 31.3% of the patients, and was significantly associated with liver metastasis. Patients with positive CD44v9 expression had a lower 5-year survival rate (62.3%) than those with negative CD44v9 expression (82.8%, p < 0.001). Cox regression analysis identified CD44v9 expression and high CEA levels (≥5 ng/mL) as poor prognostic factors, while negative CD44v9 expression and low CEA levels (<5 ng/mL) were associated with favorable prognosis (hazard ratio = 0.285, p = 0.006). These results suggest that a combination of CD44v9 mRNA expression in CTCs and serum CEA levels could serve as a valuable prognostic marker for CRC, potentially enhancing the accuracy of prognosis predictions. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (KOA) is characterized by low-grade inflammation, loss of articular cartilage, subchondral bone remodeling, synovitis, osteophyte formation, and pain. Strong, continuous pain may indicate the need for joint replacement in patients with end-stage OA, although postoperative pain (POP) of at least a two-month duration persists in 10–40% of patients with OA. Study purpose: The inflammation observed in joint tissues is linked to pain caused by the production of proinflammatory cytokines. Since the biosynthesis of cytokines requires energy, their production is supported by extensive metabolic conversions of carbohydrates and fatty acids, which could lead to a disruption in cellular homeostasis. Therefore, this study aimed to investigate the association between POP development and disturbances in energy metabolic conversions, focusing on carbohydrate and fatty acid metabolism. Methods: Peripheral blood samples were collected from 26 healthy subjects and 50 patients with end-stage OA before joint replacement surgery. All implants were validated by orthopedic surgeons, and patients with OA demonstrated no inherent abnormalities to cause pain from other reasons than OA disease, such as malalignment, aseptic loosening, or excessive bleeding. Pain levels were assessed before surgery using the visual analogue scale (VAS) and neuropathic pain questionnaires, DN4 and PainDETECT. Functional activity was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Three and six months after surgery, pain indices according to a VAS of 30 mm or higher were considered. Total RNA isolated from whole blood was analyzed using quantitative real-time RT-PCR (qRT-PCR) for the expression of genes related to carbohydrate and fatty acid metabolism. Protein levels of the examined genes were measured using an ELISA in the peripheral blood mononuclear cells (PBMCs). We used qRT-PCR because it is the most sensitive and reliable method for gene expression analysis, while an ELISA was used to confirm our qRT-PCR results. Key findings: Among the study cohort, 17 patients who reported POP demonstrated significantly higher (p < 0.05) expressions of the genes PKM2, LDH, SDH, UCP2, CPT1A, and ACLY compared to pain-free patients with KOA. Receiver-operating characteristic (ROC) curve analyses confirmed the association between these gene expressions and pain development post-arthroplasty. A principle component analysis identified the prognostic values of ACLY, CPT1A, AMPK, SDHB, Caspase 3, and IL-1β gene expressions for POP development in the examined subjects. Conclusion: These findings suggest that the disturbances in energy metabolism, as observed in the PBMCs of patients with end-stage KOA before arthroplasty, may contribute to POP development. An understanding of these metabolic processes could provide insights into the pathogenesis of KOA. Additionally, our findings can be used in a clinical setting to predict POP development in end-stage patients with KOA before arthroplasty. [ABSTRACT FROM AUTHOR]

Periprosthetic joint infections (PJIs) are a prominent subject of discussion in orthopedics and are frequently debated at conferences and congresses. In the context of PJIs affecting the knee, the decision between following a one-stage or two-stage treatment approach has historically been a pivotal consideration. The first option is limited by indications and potentially devastating complications in case of failure, whereas the second is widely accepted as the gold standard. Initially, the spacer was conceived solely to restore and maintain knee space after removal of the implant. An articulating spacer was introduced to mitigate patient limitations and improve knee function and quality of life. Two main types of articulating spacers are utilized in knee PJI treatment: the mold spacer and the metal-on-poly spacer. This text outlines a technique for metal-on-poly spacer implants. Based on our experience and the existing literature, this approach facilitates early full weight bearing and faster recovery of the knee's range of motion, ultimately improving the quality of life after surgery, thus allowing the spacer retention for an extended period, as suggested by the 1.5-stage revision. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) is the third-most-diagnosed cancer in males and in females, and about 20% of patients diagnosed with CRC present metastatic disease; pulmonary metastasectomy in CRC patients therefore represents a frequent scenario to be managed by thoracic surgeons. Due to the lack of randomized controlled trials among different local strategies, there is no definitive evidence about the optimal approach, although surgical resection is considered the most effective therapeutic option in this clinical scenario. Colorectal cancer is the third-most-diagnosed cancer in males and in females, representing 8% of estimated new cases, and the third cause of cancer-related death in both sexes, accounting for 9% of cancer deaths in men and 8% in women. About 20% of patients diagnosed with CRC present metastatic disease. Although lung metachronous or synchronous metastatic spread without other involved sites has been reported in only a small proportion of patients, considering that this tumor is frequently diagnosed, the clinical approach to CRC pulmonary metastases represents a major issue for thoracic surgeons and CRC oncologists. Among patients diagnosed with pulmonary metastases from CRC, about 9–12% are eligible for local treatments with radical intent, including surgical resection, SBRT (stereotactic body radiation therapy) and ablation therapy. Due to the lack of randomized controlled trials among different local strategies, there is no definitive evidence about the optimal approach, although surgical resection is considered the most effective therapeutic option in this clinical scenario. Oncological achievement of primary radical resection, the biology of primary tumor and metastatic sites, disease free interval and or progression free survival are independent prognostic factors which make it possible to define a cohort of patients which might significantly benefit from pulmonary metastasectomy. [ABSTRACT FROM AUTHOR]

Periprosthetic joint infections (PJIs) are one of the most worrying complications orthopedic surgeons could face; thus, methods to prevent them are evolving. Apart from systemic antibiotics, targeted strategies such as local antimicrobial coatings applied to prosthetics have been introduced. This narrative review aims to provide an overview of the main antimicrobial coatings available in arthroplasty orthopedic surgery practice. The search was performed on the PubMed, Web of Science, SCOPUS, and EMBASE databases, focusing on antimicrobial-coated devices used in clinical practice in the arthroplasty world. While silver technology has been widely adopted in the prosthetic oncological field with favorable outcomes, recently, silver associated with hydroxyapatite for cementless fixation, antibiotic-loaded hydrogel coatings, and iodine coatings have all been employed with promising protective results against PJIs. However, challenges persist, with each material having strengths and weaknesses under investigation. Therefore, this narrative review emphasizes that further clinical studies are needed to understand whether antimicrobial coatings can truly revolutionize the field of PJIs. [ABSTRACT FROM AUTHOR]

Delayed fracture healing can have devastating functional consequences, including pseudoarthrosis. Many factors can contribute to delayed healing, including decreased vascularity, micro-motion at the fracture site, large fracture gaps, multiple traumas at the same site, compromised metabolic status, surgical complications, and other conditions. A 61-year-old female patient was referred to our hospital with left distal humeral pseudarthrosis, accompanied by chronic pain and disability. Two years prior, the patient suffered a traumatic incident. At another medical facility, the patient underwent open reduction and internal fixation surgery with simultaneous ulnar nerve transposition. She showed favorable postoperative recovery. Unfortunately, approximately one year later, the patient sustained a second trauma to the same arm. This led to peri-implant fracture and post-traumatic aseptic degradation of the osteosynthesis system which was subsequently removed. Twelve months after the last surgery, the patient was referred to our hospital and, after thorough consideration of the therapeutic options, we decided to perform left elbow arthroplasty with left distal humeral reconstruction by using Zimmer's Comprehensive Segmental Revision System. This approach is generally reserved for tumors, and only a handful of cases of megaprostheses for non-tumoral indications have been previously reported. The surgery and perioperative care of our patient were optimal, there were no complications, and the patient recovered arm functionality following rehabilitation. [ABSTRACT FROM AUTHOR]

Megaprostheses are well-known, reliable, and effective reconstruction prostheses used in oncologic surgery for limb salvage in patients affected by primary or metastatic bone tumors. Rehabilitation plays a major role after MUTARS replacement, with the aim of improving function after surgery and maintaining the highest possible quality of life. Only a few studies have been published about the use of megaprostheses for the upper limb. The aim of this narrative review is to describe the results of functional and rehabilitative outcomes of patients affected by bone primary or metastatic bone cancer of the upper limb and surgically treated with MUTARS prostheses. A comprehensive search was conducted on PubMed and Scopus using the following MESH terms: "Mutars", "Megaprosthesis", "bone", "tumors", "metastasis", "upper limb", "rehabilitation", "outcome", "quality of life", and 10 studies were included. The most frequent oncological pathology was found to be metastases of the proximal humerus treated with modular endoprosthesis or modular reverse implants. Outcome measures used were ROM, MSTS, ASES, DASH, Constant-Murley score, Enneking score, VAS, MEP, TESS, and WOSI. Reconstruction of the proximal humerus with the MUTARS system seemed to be a valid treatment option after bone tumor resection. Rehabilitation after MUTARS surgery is very relevant, but currently, functional and rehabilitative outcomes are inadequately represented in the literature. Hence, further studies are needed to define standardized rehabilitation protocols after oncological orthopedic surgery that can be applied routinely in clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Due to the increasing incidence of hepatocellular carcinoma, which is a global problem, it is valuable to present the latest available literature that describes dietary options for preventing the development of hepatocellular carcinoma and the possibilities of dietary therapy for oncological patients. The authors firstly focus on discussing Metabolic Dysfunction-Associated Steatotic Liver Disease as a factor induced by improper dietary habits, while simultaneously suggesting the adoption of a Mediterranean diet as a model to counteract metabolic disorders resulting in HCC development. Subsequently, the authors discuss the potential for dietary modulation of autophagy processes, the necessity of supporting microbiota, the importance of providing selected vitamins and minerals, as well as compounds particularly valued for their anti-cancer properties, also observed in the case of HCC. The last aspect addressed is the consumption of products contributing to anti-tumor activity. Hepatocellular carcinoma (HCC) is diagnosed annually in nearly a million people worldwide, with approximately half of them being diagnosed at an advanced stage of the disease. Non-infectious risk factors for the development of HCC include an unbalanced lifestyle, including poor dietary choices characterized by a low intake of antioxidants, such as vitamins E and C, selenium, and polyphenols, as well as an excessive consumption of energy and harmful substances. Repeated bad dietary choices that contribute to an unbalanced lifestyle lead to the accumulation of fatty substances in the liver and to it entering an inflammatory state, which, without intervention, results in cirrhosis, the main cause of HCC. This review of the English language literature aims to present the food components that, when included in the daily diet, reduce the risk of developing HCC, as well as identifying foods that may have a carcinogenic effect on liver cells. [ABSTRACT FROM AUTHOR]

The identification of biomarkers for predicting inter-individual sorafenib response variability could allow hepatocellular carcinoma (HCC) patient stratification. SNPs in angiogenesis- and drug absorption, distribution, metabolism, and excretion (ADME)-related genes were evaluated to identify new potential predictive biomarkers of sorafenib response in HCC patients. Five known SNPs in angiogenesis-related genes, including VEGF-A, VEGF-C, HIF-1a, ANGPT2, and NOS3, were investigated in 34 HCC patients (9 sorafenib responders and 25 non-responders). A subgroup of 23 patients was genotyped for SNPs in ADME genes. A machine learning classifier method was used to discover classification rules for our dataset. We found that only the VEGF-A (rs2010963) C allele and CC genotype were significantly associated with sorafenib response. ADME-related gene analysis identified 10 polymorphic variants in ADH1A (rs6811453), ADH6 (rs10008281), SULT1A2/CCDC101 (rs11401), CYP26A1 (rs7905939), DPYD (rs2297595 and rs1801265), FMO2 (rs2020863), and SLC22A14 (rs149738, rs171248, and rs183574) significantly associated with sorafenib response. We have identified a genetic signature of predictive response that could permit non-responder/responder patient stratification. Angiogenesis- and ADME-related genes correlation was confirmed by cumulative genetic risk score and network and pathway enrichment analysis. Our findings provide a proof of concept that needs further validation in follow-up studies for HCC patient stratification for sorafenib prescription. [ABSTRACT FROM AUTHOR]

There is no unified approach for restoring the suprapatellar quadriceps tendon and covering tissue defects simultaneously. In this case report, we present the pedicled myocutaneous rectus femoris flap as one effective approach in two cases with extensive loss or impairment of the suprapatellar muscle–tendon structures after trauma-related suprapatellar quadriceps tendon rupture and multiple reconstruction attempts. Additionally, we provide a literature review of the reconstructive use of the functional pedicled myocutaneous rectus femoris flap. Methods: Two male patients, 48 and 74 years old, with extensive loss or impairment of the suprapatellar muscle–tendon structures due to multiple reconstruction attempts, underwent restoration of the knee extension with a pedicled myocutaneous rectus femoris flap. Results: Three months after reconstruction, both patients were able to walk freely, unaided. After a six-month follow-up, the free passive mobility of the knee joint was restored, and the active extension of the knee joint was possible in both patients. Conclusion: The authors conclude that the pedicled rectus femoris flap is a reliable method for the restoration of knee extension, with excellent functional results in cases of suprapatellar tendon lesions. Further to the functional restoration, this technique has the additional advantage of simultaneously achieving coverage of soft-tissue defects, while a direct closure of the donor site is possible. Elderly patients and patients with relevant comorbidities or multiple revisions may especially benefit from this technique. [ABSTRACT FROM AUTHOR]

Robotic-arm-assisted total knee arthroplasty (RATKA) with the MAKO system minimizes deviations in implant alignment and yields superior precision in implant position compared to a manual total knee arthroplasty. In this comprehensive commentary, we present and categorize the limitations and pitfalls of the procedure and we also provide recommendations for avoiding each limitation. The main surgeon-related limitations include prolonged operation duration, loose insertion of the checkpoints and pins, wrong registration and mapping, and damage to soft tissues during bone cutting. The system-related issues include the interruptions of the saw-cutting due to vibrations, specifications for the operating room floor and power supply, the high cost of the system, as well as the cost of each operation due to the extra implants, inability to use the system with various prostheses, wireless connection interruptions between the system's components, and hardware issues with the six joints of the robotic device. In order to circumvent the potential challenges in this surgical procedure, it is essential to possess sufficient experience and undergo comprehensive training. Maintaining continuous awareness of the additional implants throughout the entire operation and prioritizing the preservation of soft tissues are of paramount significance. A profound comprehension of the system and its inherent constraints can also prove to be pivotal in certain situations. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) is a serious health problem, becoming the third most prevalent cancer and the second leading cause of cancer-related deaths. Early diagnosis is crucial as the patients have a high survival rate if the disease is detected in time. However, current CRC screening methods are either invasive or lack sensitivity and specificity, demonstrating the need to identify new ways to detect this disease. In this context, several studies have looked at small molecules present in biological fluids that can inform about the presence of tumors. Of all the biological fluids that can be analyzed, feces probably represent the fluid with the best access, as it is obtained non-invasively and has direct contact with the intestinal mucosa. This review summarizes and discusses recent advancements in the identification of potential new markers for CRC, with a focus on fecal samples. Colorectal cancer (CRC) is one of the most diagnosed cancers worldwide, with a high incidence and mortality rate when diagnosed late. Currently, the methods used in healthcare to diagnose CRC are the fecal occult blood test, flexible sigmoidoscopy, and colonoscopy. However, the lack of sensitivity and specificity and low population adherence are driving the need to implement other technologies that can identify biomarkers that not only help with early CRC detection but allow for the selection of more personalized treatment options. In this regard, the implementation of omics technologies, which can screen large pools of biological molecules, coupled with molecular validation, stands out as a promising tool for the discovery of new biomarkers from biopsied tissues or body fluids. This review delves into the current state of the art in the identification of novel CRC biomarkers that can distinguish cancerous tissue, specifically from fecal samples, as this could be the least invasive approach. [ABSTRACT FROM AUTHOR]

Prosthetic joint infection (PJI) is the most common mode of failure of megaprostheses, yet the literature on the topic is scarce, and studies report conflicting data regarding the optimal treatment strategy. Patients with megaprostheses PJI are often immunosuppressed, and surgeons must balance the trade-off between treatment efficacy and morbidity associated with the surgery aiming for infection eradication. Our review on megaprostheses PJI focuses on two axes: (1) risk factors and preventative strategies; and (2) surgical strategies to manage this condition. Risk factors were classified as either unmodifiable or modifiable. Attempts to decrease the risk of PJI should target the latter group. Strategies to prevent PJI include the use of silver-coated implants, timely discontinuation of perioperative antibiotic prophylaxis, and adequate soft tissue coverage to diminish the amount of dead space. Regarding surgical treatment, main strategies include debridement, antibiotics, implant retention (DAIR), DAIR with modular component exchange, stem retention (DAIR plus), one-stage, and two-stage revision. Two-stage revision is the "gold standard" for PJI in conventional implants; however, its success hinges on adequate soft tissue coverage and willingness of patients to tolerate a spacer for a minimum of 6 weeks. DAIR plus and one-stage revisions may be appropriate for a select group of patients who cannot endure the morbidity of two surgeries. Moreover, whenever DAIR is considered, exchange of the modular components should be performed (DAIR plus). Due to the low volume of megaprostheses implanted, studies assessing PJI should be conducted in a multi-institutional fashion. This would allow for more meaningful comparison of groups, with sufficient statistical power. Level of evidence: IV. [ABSTRACT FROM AUTHOR]

Few data are available about results after procedures of resection and megaprosthesis at the hip in very elderly patients. The aim of our study was to ascertain survival and complications in patients aged 80 or older undergoing these major orthopedic procedures. A consecutive series of 27 procedures in 26 patients aged 80–93 years was evaluated. In total, 15 procedures were performed due to oncological diseases, 6 were performed following joint arthroplasty failures or periprosthetic fractures, and 6 were performed after trauma or trauma sequelae. Survival of the patients ranged from 0 to 122 months. Overall survival was 56% at 3 years, 24% at 5 years, and 16% at 8 years. An early postoperative death during the first 3 months occurred in five patients (18.5%). The only preoperative parameter negatively affecting survival was preoperative hemoglobin lower than 11 g/dL. Local complications were similar to reported rates in all-age patients' series. In our experience, resection and megaprosthetic reconstruction can also be a valid choice in very elderly patients, with 56% of patients living more than two years from surgery and 24% more than five. Nevertheless, early postoperative deaths are frequent. A multidisciplinary evaluation of frailty of the patient must be accomplished, and patients and relatives must be informed about the risks of the procedure. [ABSTRACT FROM AUTHOR]

Chemoresistance to standard neoadjuvant treatment commonly occurs in locally advanced breast cancer, particularly in the luminal subtype, which is hormone receptor-positive and represents the most common subtype of breast cancer associated with the worst outcomes. Identifying the genes associated with chemoresistance is crucial for understanding the underlying mechanisms and discovering effective treatments. In this study, we aimed to identify genes linked to neoadjuvant chemotherapy resistance in 62 retrospectively included patients with luminal breast cancer. Whole RNA sequencing of 12 patient biopsies revealed 269 differentially expressed genes in chemoresistant patients. We further validated eight highly correlated genes associated with resistance. Among these, solute carrier family 12 member 1 (SLC12A1) and glutamate ionotropic AMPA type subunit 4 (GRIA4), both implicated in ion transport, showed the strongest association with chemoresistance. Notably, SLC12A1 expression was downregulated, while protein levels of glutamate receptor 4 (GLUR4), encoded by GRIA4, were elevated in patients with a worse prognosis. Our results suggest a potential link between SLC12A1 gene expression and GLUR4 protein levels with chemoresistance in luminal breast cancer. In particular, GLUR4 protein could serve as a potential target for drug intervention to overcome chemoresistance. [ABSTRACT FROM AUTHOR]

Background: The number of total knee replacements performed annually is steadily increasing. Parallel options for postoperative care are decreasing, which reduces patient satisfaction. External devices to support physical rehabilitation and health monitoring will improve patient satisfaction and postoperative care. Methods: In a prospective, international multicenter study, patients were asked to use an external motion sensor and a smartphone application during the postoperative course of primary total knee arthroplasty. The collected data were transferred to a data platform, allowing for the real-time evaluation of patient data. Results: In three participating centers, 98 patients were included. The general acceptance of using the sensor and app was high, with an overall compliance in study participation rate of up to 76%. The early results showed a significant improvement in the overall quality of life (p < 0.001) and significant reductions in pain (p < 0.01) and depression (p < 0.001). Conclusions: The early results of this clinical and multicenter study emphasize that there is a high interest in and acceptance of digital solutions in patients' treatment pathways. Motion sensor and smartphone applications support patients in early rehabilitation. [ABSTRACT FROM AUTHOR]

Gastric cancer presents substantial management challenges, and the advent of immunotherapy has ignited renewed hope among patients. Nevertheless, a significant proportion of patients do not respond to immunotherapy, and adverse events associated with immunotherapy also occur on occasion, underscoring the imperative to identify suitable candidates for treatment. Several biomarkers, including programmed death ligand-1 expression, tumor mutation burden, mismatch repair status, Epstein–Barr Virus infection, circulating tumor DNA, and tumor-infiltrating lymphocytes, have demonstrated potential in predicting the effectiveness of immunotherapy in gastric cancer. However, the quest for the optimal predictive biomarker for gastric cancer immunotherapy remains challenging, as each biomarker carries its own limitations. Recently, multi-omics technologies have emerged as promising platforms for discovering novel biomarkers that may help in selecting gastric cancer patients likely to respond to immunotherapy. The identification of reliable predictive biomarkers for immunotherapy in gastric cancer holds the promise of enhancing patient selection and improving treatment outcomes. In this review, we aim to provide an overview of clinically established biomarkers of immunotherapy in gastric cancer. Additionally, we introduce newly reported biomarkers based on multi-omics studies in the context of gastric cancer immunotherapy, thereby contributing to the ongoing efforts to refine patient stratification and treatment strategies. [ABSTRACT FROM AUTHOR]

Periprosthetic joint infections (PJI) and fracture-related infections (FRI) of the distal femur (DF) may result in massive bone defects. Treatment options include articulated silver-coated (SC) megaprosthesis (MP) in the context of a two-stage protocol. However, there is limited evidence in the literature on this topic. A retrospective review of the prospectively maintained databases of three Institutions was performed. Forty-five patients were included. The mean follow-up time was 43 ± 17.1 months. Eight (17.8%) patients had a recurrent infection. The estimated recurrence-free survival rate was 91.1% (93.5% PJI vs. 85.7% FRI) 2 years following MP implantation, and 75.7% (83.2% PJI vs. 64.3% FRI; p = 0.253) after 5 years. No statistically relevant difference was found according to the initial diagnosis (PJI vs. FRI). Among possible risk factors, only resection length was found to significantly worsen the outcomes in terms of infection control (p = 0.031). A total of eight complications not related to infection were found after reimplantation, but only five of them required further surgery. Above-the-knee amputation was performed in two cases (4.4%), both for reinfection. Articulated DF SC MP in a two-stage protocol is a safe and effective treatment for chronic knee infection with severe bone loss. [ABSTRACT FROM AUTHOR]

Basal thumb arthritis is a painful and debilitating pathology that can severely reduce a patients' quality of life. Common therapies include oral pain control, local steroid injections and/or surgery. Yet, therapeutic data on long-term improvement and even cartilage repair are scarce. This review aims to present the currently available literature on novel therapies for basal thumb arthritis, including platelet-rich plasma (PRP), fat grafting and phototherapy, and investigate their potential efficacy. The entire OVID database and PubMed were searched for studies containing the topics PRP injection, lipofilling, laser treatment and regenerative treatment for carpometacarpal arthritis. Seven studies on the effect of fat tissue on basal thumb arthritis were found. Four authors reported on PRP injections, one RCT examined a combinational treatment of PRP and fat grafting, another phototherapy for the thumb joint and one prospective trial on chondrocyte transplantation was found. Pain improvement and decreased impairment were reported in the majority of PRP and/or fat grafting studies as well as after chondrocyte implantation. Phototherapy did not significantly improve the condition. This review revealed that only limited data on regenerative therapies for carpometacarpal arthritis are currently available, yet PRP and lipofilling show promising results and merit further investigation. [ABSTRACT FROM AUTHOR]

Additively manufactured (AM) porous titanium implants may have an increased risk of implant-associated infection (IAI) due to their huge internal surfaces. However, the same surface, when biofunctionalized, can be used to prevent IAI. Here, we used a rat implant infection model to evaluate the biocompatibility and infection prevention performance of AM porous titanium against bioluminescent methicillin-resistant Staphylococcus aureus (MRSA). The specimens were biofunctionalized with Ag nanoparticles (NPs) using plasma electrolytic oxidation (PEO). Infection was initiated using either intramedullary injection in vivo or with in vitro inoculation of the implant prior to implantation. Nontreated (NT) implants were compared with PEO-treated implants with Ag NPs (PT-Ag), without Ag NPs (PT) and infection without an implant. After 7 days, the bacterial load and bone morphological changes were evaluated. When infection was initiated through in vivo injection, the presence of the implant did not enhance the infection, indicating that this technique may not assess the prevention but rather the treatment of IAIs. Following in vitro inoculation, the bacterial load on the implant and in the peri-implant bony tissue was reduced by over 90% for the PT-Ag implants compared to the PT and NT implants. All infected groups had enhanced osteomyelitis scores compared to the noninfected controls. [ABSTRACT FROM AUTHOR]