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Introduction and Importance: Metastatic cancer of the umbilicus is an uncommon and rare presentation., Case Presentation: Our interest for the clinical outcomes of umbilical metastases from colon cancer arose after a 60-years old lady with ulcerated umbilical lesion came to our clinic. She was seen in several other clinics, and the diagnoses of infection of the umbilical region and/or of umbilical hernia were made. She was asymptomatic and in good clinical conditions. A complete evaluation led to the diagnosis of adenocarcinoma in the caecum with umbilical metastasis. During the hospital admission she underwent emergency colectomy for acute obstruction. An uneventful right colectomy was performed, but the lady died 21 months after surgery for diffuse metastases., Clinical Discussion: We performed a literature review of reports describing patients with umbilical metastases. Median survival rate was 7 months from the time of diagnosis of the umbilical metastasis (5 months in clinical reports and 8 months in autopsy studies). Observed survival rates were higher for patients with primary ovarian cancer (18 months), and endometrium (9 months). Median survival rate was 8 months in case of primary colon cancer. Chemotherapy and surgery allowed acceptable survival and quality of life in 8 patients with umbilical metastasis from colon cancer., Conclusion: Clinical experience suggests that an aggressive approach may offer to selected groups of patients with umbilical metastasis from abdominal cancer acceptable quality of life and improved survival probabilities., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest or commercial ties., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The aim of our study was to determine a correlation between decrease of levels of atmospheric pollution (as determined by air levels of Particulate Matters with a diameter equal or less to 2.5 microns) and reduced number of hospital admissions and operations for patients with common cardiovascular diseases in Italy., Methods: We correlated number of hospital admissions and cardiovascular operations and atmospheric levels of PM.2.5 from 2015 to 2019 in Italy. This time interval was chosen because the possibility to analyze data about other established cardiovascular risk factors as reported by the European Union Eurostat., Results: A statistically significant decrease of hospital admissions for cardiovascular and pulmonary emergencies was registered in Italy from 2015 to 2019 (p<0.01). The number also of cardiovascular operations showed a trend towards reduction with improved 30-days results, without reaching a statistically significant correlation (p =0.10). In the period 2015-2019, there was a steady decrease of atmospheric levels of pM2.5, either in urban or rural areas (p<0.01). The decrease of atmospheric levels of PMs2.5 started in 2010 and continued with a steady trend until the year 2019. In the period 2015-2019 exposure of the Italian population to established risk factors for cardiovascular diseases showed a small increase. The number of admissions and operations for non- cardiovascular and non-pulmonary diseases remained unchanged in the period 2015-2019., Conclusions: The findings of our study underline the possibility that decrease of atmospheric pollution may determine almost immediate decrease of cardiovascular and pulmonary diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of interest: None declared.

The objective of this study was to determine the correlation between adherence to cancer screening programs and earlier diagnosis of the 14 most common types of cancers in the adult population, before and during the COVID-19 pandemic. National data concerning number of admissions and operations in Italy for adult patients admitted with oncologic problems during the COVID-19 pandemic (2020 to 2022) and in the pre-pandemic period (2015 to 2019) were analyzed. We selected 14 types of cancer that present the most common indications for surgery in Italy. This study included 1,365,000 adult patients who had surgery for the 14 most common types of cancer in the period 2015-2022, and interviews concerning adherence rates to screening for breast, colorectal, and cervical cancer were conducted for 133,455 individuals. A higher decrease in the number of operations for the 14 types of cancer (-45%) was registered during the first three acute phases of the pandemic, and it was more evident for screenable cancers like breast, colorectal, and cervical cancer ( p < 0.001). During the first year of the COVID-19 pandemic, the number of screened individuals for breast, colorectal, and cervical cancer decreased by 33.8% (from 7,507,893 to 4,969,000) and the number of diagnoses and operations for these three types of cancer decreased by 10.5% (from 107,656 to 96,405). The increase and return to normality of the number of screened individuals in the last year of the pandemic (2022) and in the first post-pandemic year (2023) was associated with a return to the pre-pandemic levels of diagnoses and operations. The adherence rates were lower for individuals living in rural areas, with low socio-economic status, and unmarried persons; however, the most statistically significant factor for reduced adherence was a lower level of educational attainment. Free screening through nationally organized programs reduced social disparities. There were no significant differences between the pre-pandemic and pandemic periods for several types of cancers (stomach, esophagus, pancreas, liver) that are diagnosed for the occurrence of symptoms and for which nationally organized programs might increase the possibility of earlier diagnosis and improved clinical outcomes. Education, information, and appropriate expenditure for preventive care have the potential to reduce cancer mortality. Nationally organized screening programs for several types of cancers, which are often detected for the occurrence of symptoms, may increase the possibility of diagnosis at earlier stages.

Background: The unexpected virulence of the COVID19 pandemic brought to significant changes of generally accepted therapeutic approaches. The consequences of these changes were difficult to define during the pandemic period., Methods: We analyzed the National Registries including 97% of hospital admissions in Italy, regarding data describing number of operations for aortic valve implantation or repair, carotid and coronary revascularization, AAA repair, and lower limb arterial reconstruction performed in the period 2015 to 2019 and in the pandemic years 2020, 2021, and 2022. Primary outcomes were number and type of surgical procedures, 30-days operative mortality., Results: During the three years of the pandemic there was a statistically significant increase of the number of all-causes deaths in comparison with the mean of the previous five years (2015-2019). In Italy there was a total increase of all causes-deaths of 251.911 (+105900 in 2020; +66929 in 2021; and +79082 in 2022), and 73% of the excess of deaths was related with COVID19 infection and 27% occurred in COVID 19 negative patients. During the first year of the pandemic, worse clinical outcomes for hospitalized patients with CVD were registered. The medical system responded adequately and in the following two pandemic years clinical outcomes for hospitalized patients were similar with those of the pre-pandemic period., Conclusions: The unexpected virulence of COVID19 pandemic determined worse clinical outcomes for patients with CVD during the first year. The adopted preventive measures allowed in the following two pandemic years improved clinical outcomes, similar with those of the pre-pandemic period., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: the aim of our study was to analyze exposure of the general population to established risk factors for cardiovascular disease (CVD), which might have determined the trend towards increased mortality rates related with CVD from 2015 to 2019 in USA., Material and Methods: We Analyzed epidemiological of data from the US National Health and Nutrition Examination Survey and from the European Health Interview Survey to determine trends for exposure to several established risk factors for CVD from 2000 to 2018-2019. Trends of prevalence of obesity, arterial hypertension, cigarettes smoking, high cholesterol level, diabetes in the period 2000 to 2018-2019 in USA were correlated with age adjusted mortality and burden related with CVD. We correlated these trends also with educational attainment, family income and national expenditure for preventive care., Results: Cardiovascular Diseases Related Mortality And Burden Decreased Significantly In Usa In The Period 2000-2015; In The Period 2015-2019 there was a trend towards increasing mortality rates. The trend in the period 2015-2019 was associated with increased exposure to several established risk factors for CVD: obesity, diabetes, cigarettes smoking and arterial hypertension. Level of education attainment and family income, and national health expenditure for information, education and counseling were statistically correlated with reduced exposure to established risk factors. Similar trends were present in Western European countries., Conclusions: Attention is required to improve education and communication, health access and care for people with poor economic conditions, homeless, minorities, to reduce CVD related mortality and burden., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background and Introduction: Lung cancer is a prevalent and deadly disease globally. Non-small cell lung cancer (NSCLC) is the most common subtype, comprising 85% of cases., Case Report: A 65-year-old male ex-smoker presented to our facility with a nocturnal cough. Various investigations revealed that he had metastatic NSCLC, for which he underwent chemotherapy with cisplatin and gemcitabine, followed by immunotherapy with Nivolumab. He achieved a complete response to the therapy and has remained free from recurrence for over 7 years since the initial diagnosis., Discussion and Conclusions: The treatment of metastatic NSCLC remains a significant therapeutic challenge, but the implementation of new therapeutic techniques has expanded the possibilities of achieving complete and durable eradication of the disease.

Different xenogeneic inorganic bone substitutes are currently used as bone grafting materials in oral and maxillo-facial surgery. The aim of the present study was to determine the physicochemical properties and the in vivo performance of an anorganic equine bone (AEB) substitute. AEB is manufactured by applying a process involving heating at >300 °C with the aim of removing all the antigens and the organic components. AEB was structurally characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray fluorescence (XRF), and Fourier-transformed infrared (FT-IR) spectroscopy and compared to the anorganic bovine bone (ABB). In order to provide a preliminary evaluation of the in vivo performance of AEB, 18 bone defects were prepared and grafted with AEB (nine sites), or ABB (nine sites) used as a control, in nine Yucatan Minipigs. De novo bone formation, residual bone substitute, as well as local inflammatory and tissue effects were histologically evaluated at 30 and 90 days after implantation. The structural characterization showed that the surface morphology, particle size, chemical composition, and crystalline structure of AEB were similar to cancellous human bone. The histological examination of AEB showed a comparable pattern of newly formed bone and residual biomaterial to that of ABB. Overall, the structural data and pre-clinical evidence reported in the present study suggests that AEB can be effectively used as bone grafting material in oral surgery procedures.

When diabetes mellitus is not properly controlled with drugs and a healthy lifestyle, it exposes patients with advanced peripheral arterial disease or critical limb ischaemia (CLI) to the most serious complications, in particular lower limb ulcers. Surgical or endovascular treatments represent the first line of intervention; in addition, the adequate management of ulcers can guarantee not only a faster wound healing but also the improvement of the patient's prognosis. To speed up this process, negative pressure wound therapy (NPWT), platelet-rich plasma (PRP), and other advanced moist wound dressing have been proposed. During Coronavirus disease 2019 (COVID-19) pandemic, many patients with CLI and diabetes mellitus had difficult access to advanced treatments with a significant reduction in life expectancy. We report the cases of patients with non-healing ulcers and CLI treated with an empiric multistage approach after successful endovascular revascularisation; the postoperative course was eventful in all patients, and foot ulcers are currently in an advanced state of healing. The association between adequate revascularisation, systemic anti-inflammatory, and antibiotic therapy with the multistage advanced medications ensures healing of ulcers, limb salvage, and improvement of patient prognosis., (© 2020 Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Background: Prenatal surgery represents a multifactorial stressor event for mother and fetus. The stress response to fetal surgery was evaluated by measuring maternal plasma and amniotic fluid (AF) cortisol levels in the myelomeningocele (MMC) sheep model., Subjects and Methods: Pregnant ewes (n = 8) underwent general anesthesia for MMC-induction (step 1: 75 d gestation), surgical defect repair (step 2: 110 d gestation), and delivery (step 3: 140 d gestation). Maternal blood samples were taken before surgery (surgical stage T1), after laparotomy and uterine exposure (surgical stage T2), at the end of the procedure (surgical stage T3). Fetal stress was evaluated by measuring cortisol levels in AF after hysterotomy at steps 1-3., Results: Maternal cortisol concentrations at T2 and T3 increased compared with T1 (p = 0.019 and p = 0.046). AF cortisol response increased from 1 to 3 surgical steps and during pregnancy. The AF cortisol level was lower than maternal serum levels (induction p < 0.001; repair p < 0.001; caesarean section p < 0.001)., Conclusions: Hysterotomy was the most stressful event in the ewes. Fetuses seemed to be partially protected from the high maternal cortisol levels. The fetal stress response to prenatal surgery increased with gestational age. Pain perception development, fetal maturation, and "pain memory" are probably associated with this increase.

A novel three-dimensional bicomponent substitute made of collagen type I and hydroxyapatite was tested for the repair of osteochondral lesions in a swine model. This scaffold was assembled by a newly developed method that guarantees the strict integration between the organic and the inorganic parts, mimicking the biological tissue between the chondral and the osseous phase. Thirty-six osteochondral lesions were created in the trochlea of six pigs; in each pig, two lesions were treated with scaffolds seeded with autologous chondrocytes (cell+group), two lesions were treated with unseeded scaffolds (cell- group), and the two remaining lesions were left untreated (untreated group). After 3 months, the animals were sacrificed and the newly formed tissue was analyzed to evaluate the degree of maturation. The International Cartilage Repair Society (ICRS) macroscopic assessment showed significantly higher scores in the cell- and untreated groups when compared with the cell+ group. Histological evaluation showed the presence of repaired tissue, with fibroblast-like and hyaline-like areas in all groups; however, with respect to the other groups, the cell- group showed significantly higher values in the ICRS II histological scores for "cell morphology" and for the "surface/superficial assessment." While the scaffold seeded with autologous chondrocytes promoted the formation of a reparative tissue with high cellularity but low glycosaminoglycans (GAG) production, on the contrary, the reparative tissue observed with the unseeded scaffold presented lower cellularity but higher and uniform GAG distribution. Finally, in the lesions treated with scaffolds, the immunohistochemical analysis showed the presence of collagen type II in the peripheral part of the defect, indicating tissue maturation due to the migration of local cells from the surroundings. This study showed that the novel osteochondral scaffold was easy to handle for surgical implantation and was stable within the site of lesion; at the end of the experimental time, all implants were well integrated with the surrounding tissue and no signs of synovitis were observed. The quality of the reparative tissue seemed to be superior for the lesions treated with the unseeded scaffolds, indicating the promising potential of this novel biomaterial for use in a one-stage procedure for osteochondral repair.

The human amniotic membrane (hAM), thanks to its favorable properties, including anti-inflammatory, anti-fibrotic and pro-regenerative effects, is a well-known surgical material for many clinical applications, when used both freshly after isolation and after preservation. We have shown previously that hAM patching is a potential approach to counteract liver fibrosis. Indeed, when fresh hAM was used to cover the liver surface of rats with liver fibrosis induced by the bile duct ligation (BDL) procedure, the progression and severity of fibrosis were significantly reduced. Since cryopreservation enables safety and long-term storage of hAM but may influence its functional properties, here we compared the anti-fibrotic effects of fresh and cryopreserved hAM in rats with BDL-induced liver fibrosis. After BDL, the rat liver was covered with a piece of fresh or cryopreserved hAM, or left untreated. Six weeks later, the degree of liver fibrosis was assessed histologically using the Knodell and the METAVIR scoring systems. Digital image analysis was used to quantify the percentage of the areas of each liver section displaying ductular reaction, extracellular matrix (ECM) deposition, activated myofibroblasts and hepatic stellate cells (HSCs). Liver collagen content was also determined by spectrophotometric technique. The degree of liver fibrosis, ductular reaction, ECM deposition, and the number of activated myofibroblasts and HSCs were all significantly reduced in hAM-treated rats compared to control animals. Fresh and cryopreserved hAM produced the same anti-fibrotic effects. These findings indicate that cryopreservation maintains the anti-fibrotic properties of hAM when used as a patch to reduce the severity of liver fibrosis.

The differentiated state of mature cells of adult organisms is achieved and maintained through the epigenetic regulation of gene expression, which consists of several mechanisms including DNA methylation. The advent of induced pluripotent stem cell technology enabled the conversion of adult cells into any other cell type passing through a stable pluripotency state. However, indefinite pluripotency is unphysiological, inherently labile, and makes cells prone to culture-induced alterations. The direct conversion of one cell type to another without an intermediate pluripotent stage is also possible but, at present, requires the viral transfection of appropriate transcription factors, limiting its therapeutic potential. The aim of this study was to investigate whether it is possible to achieve the direct conversion of an adult cell by exposing it to a demethylating agent immediately followed by differentiating culture conditions. Adult human skin fibroblasts were exposed for 18 h to the DNA methyltransferase inhibitor 5-azacytidine, followed by a three-step protocol for the induction of endocrine pancreatic differentiation that lasted 36 d. At the end of this treatment, 35 ± 8.9% fibroblasts became pancreatic converted cells that acquired an epithelial morphology, produced insulin, and then released the hormone in response to a physiological glucose challenge in vitro. Furthermore, pancreatic converted cells were able to protect recipient mice against streptozotocin-induced diabetes, restoring a physiological response to glucose tolerance tests. This work shows that it is possible to convert adult fibroblasts into insulin-secreting cells, avoiding both a stable pluripotent stage and any transgenic modification.

Background: In the last few years, several attempts have been made to treat large bone loss, including the use of tissue engineering with osteoinductive scaffolds and cells. This study highlights the role of mesenchymal stem cells from adipose tissue (ASCs; adipose-derived stem cells) in a rabbit bone regeneration model., Methods: We compared the neoformed bone tissues achieved by treating critical tibial defects with either hydroxyapatite alone (HA, group I) or hydroxyapatite-autologous ASC constructs (ASCs-HA, group II), investigating their histomorphometric, immunohistochemical and biomechanical properties., Results: After eight weeks of follow-up, we observed advanced maturation and a spatial distribution of new bone that was more homogeneous in the inner parts of the pores in group II, not just along the walls (as seen in group I). The new tissue expressed osteogenic markers, and biomechanical tests suggested that the newly formed bone in group II had a higher mineral content than that in group I. Although variability in differentiation was observed among the different cell populations in vitro, no differences in bone healing were observed in vivo; the variability seen in vitro was probably due to local microenvironment effects., Conclusions: Tibial defects treated with rabbit ASCs-HA showed an improved healing process when compared to the process that occurred when only the scaffold was used. We suggest that implanted ASCs ameliorate the bone reparative process either directly or by recruiting resident progenitor cells.

Introduction: Adipose-derived stem cells (ASCs) are progenitor cells used in bone tissue engineering and regenerative medicine. Despite subcutaneous adipose tissue being more abundant, the buccal fat pad (BFP) is easily accessible for dentists and maxillofacial surgeons. For this reason, considering the need for preclinical study and the swine as an optimal animal model in tissue engineering applications, we compared the features of porcine ASCs (pASCs) from both tissue-harvesting sites., Methods: ASCs were isolated from interscapular subcutaneous adipose tissue (ScI) and buccal fat pads of six swine. Cells were characterized for their stemness and multipotent features. Moreover, their osteogenic ability when cultured on titanium disks and silicon carbide-plasma-enhanced chemical vapor-deposition fragments, and their growth in the presence of autologous and heterologous serum were also assessed., Results: Independent of the harvesting site, no differences in proliferation, viability, and clonogenicity were observed among all the pASC populations. Furthermore, when induced toward osteogenic differentiation, both ScI- and BFP-pASCs showed an increase of collagen and calcified extracellular matrix (ECM) production, alkaline phosphatase activity, and osteonectin expression, indicating their ability to differentiate toward osteoblast-like cells. In addition, they differentiated toward adipocyte-like cells, and chondrogenic induced pASCs were able to increase glycosaminoglycans (GAGs) production over time. When cells were osteoinduced on synthetic biomaterials, they significantly increased the amount of calcified ECM compared with control cells; moreover, titanium showed the osteoinductive effect on pASCs, also without chemical stimuli. Finally, these cells grew nicely in 10% FBS, and no benefits were produced by substitution with swine serum., Conclusions: Swine buccal fat pad contains progenitor cells with mesenchymal features, and they also osteo-differentiate nicely in association with synthetic supports. We suggest that porcine BFP-ASCs may be applied in preclinical studies of periodontal and bone-defect regeneration.

Objective: Neochordae implantation is a standard method for treatment of mitral valve prolapse. We describe a transcatheter technology enabling transapical endovascular chordal implantation., Methods: Six adult pigs were anesthetized. Two 10F sheaths were introduced in the femoral vessels for monitoring and intracardiac echo. After midline sternotomy, the pericardium was opened, the apex was punctured inside two 2-0 polypropylene purse strings. A 0.035 in J tipped guidewire was introduced in the left ventricle and an ultra stiff 14F sheath (guide catheter) inserted through the apex. A suction-and-suture device was introduced in the left ventricle. The mitral valve was crossed under echo guidance. Using suction, either the anterior (two cases) or posterior (four cases) leaflet was captured and a loop of 4-0 polypropylene was thrown at the edge of the leaflet. The loop, with a pledget, was exteriorized through the introducer. The introducer was removed and the purse-string tied. Under echo guidance, the neochordae suture was pulled and tied over a pledget to evoke leaflet tethering. The animals were sacrificed and gross anatomy reviewed., Results: Leaflet capture was feasible in the intended location in all cases. Following suture tethering, variable degrees of MR were obtained. At gross anatomy, the neochordae were positioned at 1-4mm from the leaflet free edge, and were firmly attached to the leaflets., Conclusions: Transcatheter endovascular neochordae implantation is feasible. A prolapse model is needed to further demonstrate feasibility under pathologic conditions. The apical approach allows easy and direct route to transcatheter beating heart minimally invasive mitral repair.