Stem cell transplantation in neurological diseases: improving effectiveness in animal models

Neurological diseases afflict a growing proportion of the human population. There are two reasons for this: first, the average age of the population (especially in the industrialised world) is increasing, and second, the diagnostic tools to detect these pathologies are now more sophisticated and can be used on a higher percentage of the population. In many cases, neurological disease has a pharmacological treatment which, as in the case of Alzheimer’s disease, Parkinson’s disease, Epilepsy, and Multiple Sclerosis can reduce the symptoms and slow down the course of the disease but cannot reverse its effects or heal the patient.In the last two decades the transplantation approach, by means of stem cells of different origin, has been suggested for the treatment of neurological diseases. The choice of slightly different animal models and the differences in methods of stem cell preparation make it difficult to compare the results of transplantation experiments. Moreover, the translation of these results into clinical trials with human subjects is difficult and has so far met with little success.This review seeks to discuss the reasons for these difficulties by considering the differences between human and animal cells (including isolation, handling and transplantation) and between the human disease model and the animal disease model.<br/

The Management of Ruptured Abdominal Aortic Aneurysms: An Ongoing Challenge

Background: despite improvements in the diagnosis and treatment of elective AAAs, ruptured abdominal aortic aneurysms (RAAAs) continue to cause a substantial number of deaths. The choice between an open or endovascular approach remains a challenge, as does postoperative complications in survivors. The aim of this manuscript is to offer an overview of the contemporary management of RAAA patients, with a focus on preoperative and intraoperative factors that could help surgeons provide more appropriate treatment. Methods: we performed a search on MEDLINE, Embase, and Scopus from 1 January 1985 to 1 May 2023 and reviewed SVS and ESVS guidelines. A total of 278 articles were screened, but only those with data available on ruptured aneurysms' incidence and prevalence, preoperative scores, and mortality rates after emergency endovascular or open repair for ruptured AAA were included in the narrative synthesis. Articles were not restricted due to the designs of the studies. Results: the centralization of RAAAs has improved outcomes after both surgical and endovascular repair. Preoperative mortality risk scores and knowledge of intraoperative factors influencing mortality could help surgeons with decision-making, although there is still no consensus about the best treatment. Complications continue to be an issue in patients surviving intervention. Conclusions: RAAA still represents a life-threatening condition, with high mortality rates. Effective screening and centralization matched with adequate preoperative risk-benefit assessment may improve outcomes

Efficacy of a dietary supplement in dogs with osteoarthritis: A randomized placebo-controlled, double-blind clinical trial

This study is a randomized, placebo-controlled, double-blinded trial performed to investigate the effects of a dietary supplement containing a mixture of Boswellia serrata Roxb., chlorophyll, green tea extract, glucosamine, chondroitin sulfate, hyaluronic acid, and further in the manuscript: non-hydrolised type II collagen in dogs with osteoarthritis (OA). A total of 40 dogs were enrolled in the study, they were randomly divided in control (CTR) and treatment (TRT) groups. The TRT group received the dietary supplement for 60 days. The CTR group received a placebo for the same number of days. All the subjects had veterinary evaluations during the trial and owners were requested to fill in questionnaires on chronic pain using the Helsinki Chronic Pain Index. The product was easy to administer and no side effects were reported. Combining results from veterinarian and owner evaluations, the tested product proved to be significantly beneficial in alleviating pain and in reducing the clinical signs in dogs with OA

Emergent management of diabetic foot problems in the modern era: Improving outcomes

Limb amputation is a consequence, and the leading complication, of diabetic foot ulcers. Prevention depends on prompt diagnosis and management. Patients should be managed by multidisciplinary teams and efforts should be focused on limb salvage (“time is tissue”). The diabetic foot service should be organized in a way to meet the patient's clinical needs, with the diabetic foot centers at the highest level of this structure. Surgical management should be multimodal and include not only revascularization, but also surgical and biological debridement, minor amputations, and advanced wound therapy. Medical treatment, including an adequate antimicrobial therapy, has a key role in the eradication of infection and should be guided by microbiologists and infection disease physicians with special interest in bone infection. Input from diabetologists, radiologists, orthopedic teams (foot and ankle), orthotists, podiatrists, physiotherapists, and prosthetics, as well as psychological counseling, is required to make the service comprehensive. After the acute phase, a well-structured, pragmatic follow-up program is necessary to adequately manage the patients with the aim to detect earlier potential failures of the revascularization or antimicrobial therapy. Considering the cost and societal impact of diabetic foot problems, health care providers should provide resources to manage the burden of diabetic foot problems in the modern er

Rupture Of Abdominal Aortic Aneurysm Due To Endograft Infection After Endovascular Aneurysm Repair (EVAR): A Case Report

Endograft infection is a rare event, with few reports in the literature. This report describes delayed infection of an aortic endoprosthesis that eventually resulted in abdominal aortic aneurysm (AAA) rupture. The procedure was performed in an angiographic suite. In the postoperative period the patient developed a central venous line infection. This appears to be the first recognized and reported case in which the infected aortic neck completely dilated due to the radial force of the stent graft

Long-term clinical outcomes in critical limb ischemia--A retrospective study of 181 patients

Critical limb ischemia (CLI) is the most severe manifestation of the peripheral arterial disease. To date, several prognostic factors have been identified but the data of long-term follow-up in real life setting are scarce. The aim of our study is to describe a large group of CLI patients and identify possible prognostic factors, in a long-term follow-up

Outcomes of three years of teamwork on critical limb ischemia in patients with diabetes and foot lesions

To evaluate the outcomes of a multidisciplinary team working on diabetic foot (DF) patients with critical limb ischemia (CLI) in a specialized center, the authors retrospectively traced all the patients admitted in their department in 3 consecutive years with a diagnosis of CLI. From January 2006 to December 2008, 245 consecutive DF patients with CLI according the TransAtlantic interSociety Consensus II criteria were included in the study. Treatment strategy was decided by a team of diabetologists, inteventional radiologists, and vascular surgeons. Technical and clinical success, mortality, and ulcer recurrence were evaluated at 6 months and at a mean follow-up of 19.5 +/- 13.4 months. Percutaneous transluminal angioplasty (PTA) was performed in 189 (77%) patients, whereas medical treatment, open surgical revascularization (OSR), and primary amputation were performed in 44 (18.3%), 11 (4.3%), and 1 (0.5%) patients, respectively. Revascularization was successful in 227/233 (97.4%) patients. At follow-up, the overall clinical success rate was 60.4%; it was significantly (P = .001) higher after revascularization (75.9%) compared with medical treatment (48.3%). During follow-up, surgical interventions in the foot were 1.5 +/- 0.4 in those treated with PTA, 1.6 +/- 0.5 in those treated with OSR, and 0.3 +/- 0.8 in those receiving medical therapy (P &lt; .05 compared with the others). Ulcer recurrence occurred in 29 (11.8%) patients: 4 (1.6%) in PTA, 2 (0.8%) in OSR, and 23 (9.4%) in the medical therapy group (P &lt; .05). Major amputation rate was 9.3%, being significantly (P = .04) lower after revascularization (5.2%) compared with medical therapy alone (13.8%). Cumulative mortality rate was 10.6%. In conclusion, this study confirms the positive role of a PTA-first approach for revascularizing the complex cases of DF with CLI in a teamwork management strategy

Long-term survival of patients with critical limb ischemia treated with iloprost: response rate and predictive criteria. A retrospective analysis of 102 patients

Critical limb ischemia (CLI) patients have poor long-term prognosis. We showed that iloprost improves outcomes (major amputation and survival) up a 5-year follow-up, but it is not known if in this length of time the survival curves, of clinical responders and non-responders, differ

Extracellular vesicles mediate the communication between multiple myeloma and bone marrow microenvironment in a NOTCH dependent way

Multiple myeloma (MM) is an incurable hematologic neoplasm, whose poor prognosis is deeply affected by the propensity of tumor cells to localize in the bone marrow (BM) and induce the protumorigenic activity of normal BM cells, leading to events associated with tumor progression, including tumor angiogenesis, osteoclastogenesis, and the spread of osteolytic bone lesions. The interplay between MM cells and the BM niche does not only rely on direct cell-cell interaction, but a crucial role is also played by MM-derived extracellular vesicles (MM-EV). Here, we demonstrated that the oncogenic NOTCH receptors are part of MM-EV cargo and play a key role in EV protumorigenic ability. We used in vitro and in vivo models to investigate the role of EV-derived NOTCH2 in stimulating the protumorigenic behavior of endothelial cells and osteoclast progenitors. Importantly, MM-EV can transfer NOTCH2 between distant cells and increase NOTCH signaling in target cells. MM-EV stimulation increases endothelial cell angiogenic ability and osteoclast differentiation in a NOTCH2-dependent way. Indeed, interfering with NOTCH2 expression in MM cells may decrease the amount of NOTCH2 also in MM-EV and affect their angiogenic and osteoclastogenic potential. Finally, we demonstrated that the pharmacologic blockade of NOTCH activation by γ-secretase inhibitors may hamper the biological effect of EV derived by MM cell lines and by the BM of MM patients. These results provide the first evidence that targeting the NOTCH pathway may be a valid therapeutic strategy to hamper the protumorigenic role of EV in MM as well as other tumors