Reducing Carbapenem-Resistant Enterobacteriaceae Using the Targeted Solution Tool: A Quality Improvement Project.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) is a worldwide urgent health problem. Hand hygiene (HH) is an effective intervention to reduce the spread of CRE. LOCAL PROBLEM: In 2017, an increase in the rate of health care-associated (HA) CRE colonization was observed in a large multiorgan transplant center in Italy. This study aimed to reduce the HA-CRE colonization rates by improving HH compliance. METHODS: A pre-/post-intervention project was conducted from November 2017 through December 2020. INTERVENTIONS: The DMAIC (Define, Measure, Analyze, Improve, and Control) framework was used to implement the HH Targeted Solution Tool (TST). RESULTS: Hand hygiene compliance increased from 49% to 76.9% after the Improve phase ( P = .0001), and to 81.9% after the second Control phase ( P = .0001). The rate of HA-CRE decreased from 24.9% to 5.6% ( P = .0001). CONCLUSIONS: Using the DMAIC framework to implement the TST can result in significant improvements in HH compliance and HA-CRE colonization rates.

Aducanumab and Its Effects on Tau Pathology: Is This the Turning Point of Amyloid Hypothesis?

Alzheimer's disease (AD) is a neurodegenerative disorder affecting millions of people around the world. The two main pathological mechanisms underlying the disease are beta-amyloid (Aß) plaques and intracellular neurofibrillary tangles (NFTs) of Tau proteins in the brain. Their reduction has been associated with slowing of cognitive decline and disease progression. Several antibodies aimed to target Aß or Tau in order to represent hope for millions of patients, but only a small number managed to be selected to participate in clinical trials. Aducanumab is a monoclonal antibody recently approved by the Food and Drug Administration (FDA), which, targeting (Aß) oligomers and fibrils, was able to reduce Aß accumulation and slow the progression of cognitive impairment. It was also claimed to have an effect on the second hallmark of AD, decreasing the level of phospho-Tau evaluated in cerebrospinal fluid (CSF) and by positron emission tomography (PET). This evidence may represent a turning point in the development of AD-efficient drugs.

Cannabinerol and NSC-34 Transcriptomic Analysis: Is the Dose Who Makes Neuronal Differentiation?

Cannabis sativa L. proved to be a source of several phytocompounds able to help patients facing different diseases. Moreover, these phytocompounds can help ameliorate general conditions and control certain unpleasant effects of diseases. Some cannabinoids, however, provided more benefits applicable to settings other than palliative care. Using the NSC-34 cell line, we evaluated the barely known phytocompound named cannabinerol (CBNR) at different doses, in order to understand its unique characteristics and the ones shared with other cannabinoids. The transcriptomic analysis suggests a possible ongoing neuronal differentiation, principally due to the activation of cannabinoid receptor 1 (CB1), to which the phosphorylation of serine-threonine protein kinase (Akt) followed, especially between 20 and 7.5 µM. The increase of Neurod1 and Map2 genes at 7.5 µM, accompanied by a decrease of Vim, as well as the increase of Syp at all the other doses, point toward the initiation of differentiation signals. Our preliminary results indicate CBNR as a promising candidate to be added to the list of cannabinoids with neuronal differentiation-enhancer properties. However, further studies are needed to confirm this initial insight.

Cannabidiol Promotes Neuronal Differentiation Using Akt and Erk Pathways Triggered by Cb1 Signaling.

Recently, the scientific community has started to focus on the neurogenic potential of cannabinoids. The phytocompound cannabidiol (CBD) shows different mechanism of signaling on cannabinoid receptor 1 (CB1), depending on its concentration. In this study, we investigated if CBD may induce in vitro neuronal differentiation after treatment at 5 µM and 10 µM. For this purpose, we decided to use the spinal cord × neuroblastoma hybrid cell line (NSC-34) because of its proliferative and undifferentiated state. The messenger RNAs (mRNAs) expression profiles were tested using high-throughput sequencing technology and Western blot assay was used to determine the number of main proteins in different pathways. Interestingly, the treatment shows different genes associated with neurodifferentiation statistically significant, such as Rbfox3, Tubb3, Pax6 and Eno2. The CB1 signaling pathway is responsible for neuronal differentiation at 10 µM, as suggested by the presence of p-ERK and p-AKT, but not at 5 µM. A new correlation between CBD, neurodifferentiation and retinoic acid receptor-related orphan receptors (RORs) has been observed.

Laparoscopic giant hiatal hernia repair with absorbable mesh.

Background: The best operative approach to large hiatal hernias still remains controversial between suture cruroplasty and prosthetic hiatal herniorrhaphy. This study aims at analysing results from a single institution in Italy in terms of subjective and objective outcomes. Methods: Retrospectively collected data of all patients that underwent laparoscopic hiatal hernia repair since 2011 were considered. Sixty-five patients were included overall; 17 of them fit the criteria of large hiatal hernia. Follow-up (FU) was assessed by visit, questionnaires and X-ray imaging. Results: No major complications occurred in the post-operative course. No patient was lost during the FU period. Out of all the patients included, 13 agreed to have an X-ray with water-soluble contrast. The questionnaires showed a 76.5% rate of satisfaction (13 patients), and the recurrence rate demonstrated by radiology was 29.4% (five patients). There were no major mesh-related complications. Conclusion: The best operative approach for large hiatal hernias remains far from standardised: There is a lack of evidence on the use of a mesh for this kind of surgery as well as substantial controversy over the definition of what a giant hiatal hernia is. Nevertheless, the results from this study and the main studies in the literature seem to be encouraging in improving giant hiatal hernia repair outcomes.

Perioperative outcomes of robotic and laparoscopic adrenalectomy: a large international multicenter experience.

BACKGROUND: The aim of the study was to describe the surgical outcomes of a retrospective series of consecutive patients treated with laparoscopic and robotic approach for adrenal masses in two tertiary referral centers. METHODS: We retrospectively gathered data of 477 patients submitted to adrenalectomy performed at two Institutions from March 2008 to February 2018 by six highly experienced surgeons. We excluded from the analysis 43 patients that had an open approach for tumors or for anesthetic contraindications to minimally invasive surgery (MIS). Patients were selected for surgery after a radiologic and an endocrinology work up. Preoperative, perioperative and postoperative data were recorded. RESULTS: Overall, 477 patients were included in the study. The robotic and the laparoscopic group included 110 and 367 patients, respectively. The preoperative characteristics were similar in both groups except for ASA score with a median (IQR) of 3 and 2 in the robotic and in the laparoscopic group, respectively (p = 0.03). Tumor size of adrenal tumors treated robotically (4, IQR 2.6-6 cm) was significantly larger than those treated laparoscopically (3, IQR 2.3-4.1 cm) (p = 0.01). The intraoperative complication rates were similar between robotic and laparoscopic groups (6.3% and 6%, respectively). The postoperative complication rate was 5.4% for robotic group and similarly 3.5% for laparoscopic adrenalectomy strategy. We analyzed the tumor ≥ 6 cm, with 29 patients in the robotic group and 43 in the laparoscopic one, with an overall complication rate of 19.5%. At multivariable analyses tumor size (OR 1.287; CI 1.128-1.468; p < 0.001) was the only independent predictor of overall complication. CONCLUSION: Adrenal tumors can be safely treated either by robotic or laparoscopic strategy. MIS seems to be feasible also in larger adrenal masses (≥ 6 cm). Tumor size represents the only predictive factors for overall complication.

SARS-CoV-2 Exposed Mesenchymal Stromal Cell from Congenital Pulmonary Airway Malformations: Transcriptomic Analysis and the Expression of Immunomodulatory Genes.

The inflammatory response plays a central role in the complications of congenital pulmonary airway malformations (CPAM) and severe coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the transcriptional changes induced by SARS-CoV-2 exposure in pediatric MSCs derived from pediatric lung (MSCs-lung) and CPAM tissues (MSCs-CPAM) in order to elucidate potential pathways involved in SARS-CoV-2 infection in a condition of exacerbated inflammatory response. MSCs-lung and MSCs-CPAM do not express angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TRMPSS2). SARS-CoV-2 appears to be unable to replicate in MSCs-CPAM and MSCs-lung. MSCs-lung and MSCs-CPAM maintained the expression of stemness markers MSCs-lung show an inflammatory response (IL6, IL1B, CXCL8, and CXCL10), and the activation of Notch3 non-canonical pathway; this route appears silent in MSCs-CPAM, and cytokine genes expression is reduced. Decreased value of p21 in MSCs-lung suggested no cell cycle block, and cells did not undergo apoptosis. MSCs-lung appears to increase genes associated with immunomodulatory function but could contribute to inflammation, while MSCs-CPAM keeps stable or reduce the immunomodulatory receptors expression, but they also reduce their cytokines expression. These data indicated that, independently from their perilesional or cystic origin, the MSCs populations already present in a patient affected with CPAM are not permissive for SARS-CoV-2 entry, and they will not spread the disease in case of infection. Moreover, these MSCs will not undergo apoptosis when they come in contact with SARS-CoV-2; on the contrary, they maintain their staminality profile.

Cannabinoids and Neurogenesis: The Promised Solution for Neurodegeneration?

The concept of neurons as irreplaceable cells does not hold true today. Experiments and evidence of neurogenesis, also, in the adult brain give hope that some compounds or drugs can enhance this process, helping to reverse the outcomes of diseases or traumas that once were thought to be everlasting. Cannabinoids, both from natural and artificial origins, already proved to have several beneficial effects (e.g., anti-inflammatory, anti-oxidants and analgesic action), but also capacity to increase neuronal population, by replacing the cells that were lost and/or regenerate a damaged nerve cell. Neurogenesis is a process which is not highly represented in literature as neuroprotection, though it is as important as prevention of nervous system damage, because it can represent a possible solution when neuronal death is already present, such as in neurodegenerative diseases. The aim of this review is to resume the experimental evidence of phyto- and synthetic cannabinoids effects on neurogenesis, both in vitro and in vivo, in order to elucidate if they possess also neurogenetic and neurorepairing properties.

Ginger, a Possible Candidate for the Treatment of Dementias?

As the human life expectancy increases, age-linked diseases have become more and more frequent. The worldwide increment of dementia cases demands medical solutions, but the current available drugs do not meet all the expectations. Recently the attention of the scientific community was attracted by natural compounds, used in ancient medicine, known for their beneficial effects and high tolerability. This review is focused on Ginger (Zingiber officinale) and explore its properties against Alzheimer's Disease and Vascular Dementia, two of the most common and devastating forms of dementia. This work resumes the beneficial effects of Ginger compounds, tested in computational in vitro and in vivo models of Alzheimer's Disease and Vascular Dementia, along with some human tests. All these evidences suggest a potential role of the compounds of ginger not only in the treatment of the disease, but also in its prevention.

Laparoscopic adrenalectomy for giant adrenal tumours: Technical considerations and surgical outcome.

BACKGROUND: Giant adrenal tumours are tumours with size ≥6 cm. These are rare cancer associated with malignancy in 25% of cases. PATIENTS AND METHODS: A retrospective review was conducted on the medical records of patients admitted to our high-volume centre of Careggi University Hospital with a giant adrenal tumour and submitted to adrenalectomy between January 2008 and December 2018. The group of patients who underwent to laparoscopic adrenalectomy was compared with a group of patients that was submitted to open adrenalectomy. RESULTS: In the past 10 years, we performed about 245 adrenalectomies for benign and malignant adrenal tumours. Fifty (20.4%) of these were giant tumours. The medium size was 9.9 cm (7-22 cm). The mean age was 57 years (21-81 years). Thirty-four (68%) of these cancers were laparoscopically removed and 16 (32%) with an open approach. The surgical outcomes in these patients were optimal if compared to the group of patients submitted to open approach in terms of good pain control, hospital stay, mean operative time and bloodless. No difference was observed about post-operative complications in the two groups. The follow-up after 30 months for malignant tumours did not show local recurrences. CONCLUSION: Our results pinpoint the advantages of performing a laparoscopic adrenalectomy for giant adrenal tumours. The tumour size is only a predictive parameter of possible malignancy, and the laparoscopic approach is a safe and feasible method in terms of surgical and oncological, only if performed by expert surgeons and in high-volume centres.

Colonic splenic flexure carcinoma: is laparoscopic segmental resection a safe enough oncological approach?

BACKGROUND: The surgical approach to the colonic splenic flexure cancer (SFC) is yet to be technically standardized. The aim of this study has been to retrospectively evaluate the oncologic long-term results of our cases comparing our data with other authors' experiences. METHODS: Clinical data of patients with SFC operated on at our institute were retrospectively analyzed. The laparoscopic approach was used in the whole series, with limited resection distally and proximally to splenic flexure and the origin ligation of left colic artery and left branch of middle colic artery. Data on the oncological long-term safety were compared to our laparoscopic series of extended right colectomy for proximal two-third transverse colon cancer and high anterior resections for sigmoid-high rectal cancer and to the main evidences in the literature, found after a comprehensive review. RESULTS: From March 2008 to May 2018, we completed 53 laparoscopic splenic flexure resections (26 female and 27 male, age 71.5 ± 15.4 years). The conversion rate was 3.8%. Most of the cases were stage II (pT3 73.5%, the mean number of lymph nodes harvested was 19.1, with positivity for malignancy in 45.3%). During the FU (43.5 months), 2 patients dropped out. Out of the 51 residual cases, 37 were alive (72.5%) and 14 are deceased (27.5%). DISCUSSION: Compared to the literature, our survival rate does not show significant differences. The other oncological outcomes seem to be comparable with the data evaluated. CONCLUSIONS: More extended resections seem not to confer an increase of the overall survival rate.

Bedside diagnostic laparoscopy for critically ill patients in the Intensive Care Unit: Retrospective study and review of literature.

BACKGROUND: Bedside diagnostic laparoscopy could be helpful in extremely critically ill patients. The aim of this retrospective study is to evaluate the safety and diagnostic accuracy of bedside diagnostic laparoscopy in the identification of intra-abdominal pathology in critically ill patients and to compare its accuracy and outcomes with the ones of laparotomy. PATIENTS AND METHODS: A retrospective review was conducted on the medical records of patients admitted to the Intensive Care Unit (ICU) of Careggi University Hospital and submitted to bedside diagnostic laparoscopy between January 2006 and May 2017. This group of patients was compared with a group of patients that were admitted to the ICU and submitted directly to explorative laparotomy for suspected intra-abdominal pathologies. RESULTS: One hundred and twenty-nine patients (M/F = 81/48, mean age = 71.64 years) underwent bedside diagnostic laparoscopy in ICU. 154 patients instead were submitted directly to explorative laparotomy in operatory room (mean age 75.70 years, M/F = 94/60). Among the 129 patients submitted to bedside laparoscopy, 53.49% were positive for intra-abdominal pathologies whereas 46.51% were negative, while among the 154 patients submitted directly to laparotomy, 76.62% were positive for intra-abdominal pathologies whereas 23.38% were negative. In 55.03% of all patients submitted to bedside laparoscopy, a non-therapeutic laparotomy was avoided, while the 33.76% of patients submitted directly to laparotomy had a non-therapeutic laparotomy that could be avoidable. CONCLUSIONS: Our results pinpoint the advantages of performing bedside diagnostic laparoscopy in the ICU setting, which can be considered an option every time there is the suspicion of an intra-abdominal pathology.

Why laparoscopists may opt for three-dimensional view: a summary of the full HTA report on 3D versus 2D laparoscopy by S.I.C.E. (Società Italiana di Chirurgia Endoscopica e Nuove Tecnologie).

BACKGROUND: Three-dimensional view in laparoscopic general, gynaecologic and urologic surgery is an efficient, safe and sustainable innovation. The present paper is an extract taken from a full health technology assessment report on three-dimensional vision technology compared with standard two-dimensional laparoscopic systems. METHODS: A health technology assessment approach was implemented in order to investigate all the economic, social, ethical and organisational implications related to the adoption of the innovative three-dimensional view. With the support of a multi-disciplinary team, composed of eight experts working in Italian hospitals and Universities, qualitative and quantitative data were collected, by means of literature evidence, validated questionnaire and self-reported interviews, applying a final MCDA quantitative approach, and considering the dimensions resulting from the EUnetHTA Core Model. RESULTS: From systematic search of literature, we retrieved the following studies: 9 on general surgery, 35 on gynaecology and urology, both concerning clinical setting. Considering simulated setting we included: 8 studies regarding pitfalls and drawbacks, 44 on teaching, 12 on surgeons' confidence and comfort and 34 on surgeons' performances. Three-dimensional laparoscopy was shown to have advantages for both the patients and the surgeons, and is confirmed to be a safe, efficacious and sustainable vision technology. CONCLUSIONS: The objective of the present paper, under the patronage of Italian Society of Endoscopic Surgery, was achieved in that there has now been produced a scientific report, based on a HTA approach, that may be placed in the hands of surgeons and used to support the decision-making process of the health providers.

Long-term functional follow-up after anterior rectal resection for cancer.

PURPOSE: This is a retrospective analysis including all of the patients that have undergone anterior resection for rectal cancer from January 1998 to December 2005 in two tertiary referral centers. The study aims to evaluate the long term functional results after low anterior resection and to identify the risk factors of postoperative bowel disorders. METHOD: Data were collected from the clinical records, and then the low anterior resection syndrome score which is a specific questionnaire to investigate the symptoms after surgery was submitted to the selected patients. Exclusion criteria were intra-abdominal rectal cancer, partial mesorectal excision, permanent stoma, recurrent local disease, and patients who declined the questionnaire. RESULTS: A total of 93 patients were included in the analysis with a median age at the diagnosis of 66 years. The median follow-up was 13.7 years, and low anterior resection syndrome was reported in 44 patients (47.5 %), with major manifestations in 19 patients (20.5 %), and minor symptoms in 25 patients (27 %). Age more than 70 years, tumor distance from the external anal verge, neoadjuvant treatment, and interval time of closing stoma are independent prognostic factors of functional disorders after surgery. CONCLUSIONS: Because of its great impact on the quality of life of these patients, it is necessary to early identify the syndrome trying to reduce its manifestations. Moreover, the symptoms seem to remain stable 1 year after surgery; hence, it is important to have an exhaustive, preoperative counseling and an integrated post-operative functional and rehabilitational follow-up in association with the oncologic pathway.

A long-term evaluation of the quality of life after laparoscopic Nissen-Rossetti anti-reflux surgery.

BACKGROUND: The quality of life (QoL) has been suggested to be the most relevant parameter to assess and monitor the long-term outcome in patients who underwent surgery for gastroesophageal reflux disease (GERD). PATIENTS AND METHODS: A retrospective evaluation was conducted on patients who underwent Laparoscopic Nissen-Rossetti Fundoplication for GERD between January 1998 and December 2010. To evaluate the long-term results a telephone interview was made using the VISICK score and the GERD-health-related QoL (HRQL) questionnaire at 1, 3, 5 years and at the end of the study. If the questionnaires resulted unsatisfactory, a complete diagnostic revaluation was performed. RESULTS: A total of 168 patients underwent laparoscopic surgery for GERD. When evaluated at the end of the study, the number of unsatisfied patients according to the VISICK score was significantly higher than the one obtained with the GERD-HRQL questionnaire. CONCLUSIONS: Many data suggest a possible recurrence of the symptoms after surgery in a long follow-up period. Our data seem to demonstrate a slight but significant trend in symptoms relapse after surgery. Considering the non-specific and specific nature of the two scores, VISICK and GERD HRQL, our result showed a significantly more relevant trend of symptoms relapse only for the non-specific ones. Such QoL scores seem to be important in selecting patients who need to be instrumentally examined. Consequently, our work proves that only a few patients out of the total number of followed up patients, are to be recalled to undergo instrumental examination.

Laparoscopic total mesorectal excision for extraperitoneal rectal cancer: long-term results.

UNLABELLED: The long-term role of laparoscopy in the treatment of rectal cancer is still controversial. The aim of the present study was to evaluate the safety, the feasibility, the perioperative outcome, and the long-term results of laparoscopic total mesorectal excision (TME) for extraperitoneal rectal cancer considering a single center series. METHODS: Data about 186 unselected consecutive patients that underwent laparoscopic TME for middle and low rectal cancer between January 2001 and December 2011 were prospectively recorded and were included in the present study. RESULTS: Distribution of TNM stage was 5 % T1, 37 % T2, 52.5 % T3, and 6 % T4. Fifty-one percent of patients have lymph node metastases. The average duration of surgery was 234 min. Fourteen patients required conversion (7.5 %). A complete microscopic excision was achieved in 169 patients (91 %). The mean hospital stay was 9 days. The overall postoperative morbidity rate was 24 %. Surgical-related complications were reported in 19 %. Overall mortality was 0.5 %. Sex, tumor level, and the presence of a stoma were the only statistically significant independent risk factors for anastomotic leakage. Median follow-up was 71 months. The 5-year overall survival rate was 77 %, with 89 % for stage 1, 81 % for stage 2, 43 % for stage 3, and 10 % for stage 4. The 5-year disease-free survival rate was 66 %. The 10-year survival rate was 54 %. Nine patients (4.8 %) experienced a pelvic recurrence. Late metastases developed in 31 patients (17.2 %). CONCLUSIONS: The study confirms the oncological safety of laparoscopic TME in a long follow-up period.

Colonic electrical stimulation for the treatment of slow-transit constipation: a preliminary pilot study.

BACKGROUND: Electrical stimulation of the gastrointestinal tract is an attractive concept. In this article we report on a procedure for electrical colonic pacing due to intramuscular electrode placement for slow-transit constipation and some preliminary results. METHODS: From January 2011 to December 2012, all consecutive patients affected by constipation and evaluated in our Pelvic Floor Center were prospectively assessed. Patients who underwent colonic electrical stimulation were evaluated for the present study. RESULTS: In the study period, 256 patients were evaluated for constipation; 58% were identified as having obstructed defecation syndrome, 27.3% with irritable bowel syndrome or mixed forms, 4% with pelvic floor dyssynergia, and 10.5% (27 patients) as having slow-transit constipation. After failure of all the maximal conventional therapies, two patients, candidates for colectomy, agreed to undergo colonic electrical stimulation before a resective treatment. Both patients were females, aged 34 and 29 years, and were suffering from severe constipation since childhood. The follow-up was 19 and 6 months. The number of bowel movements per week increased from 0.3 to 3.5 in the first patient and from 0.5 to 2.5 in the second patient. Both patients no longer needed laxatives, enemas, or any other treatment. The hospital stay was 4 days, the mean operative time was 120 min, and no complications were reported. CONCLUSIONS: Colonic pacing seems to be feasible and shows positive results. Further studies are required with a larger number of patients and a longer follow-up period to confirm the role of this promising treatment for slow-transit constipation.

Preliminary results of the influence of the in vivo use of a lymphatic dye (patent blue v) in the surgical treatment of Crohn's disease.

INTRODUCTION: Recently, the lymphatic vessels has been considered to play a key role in the pathophysiology and, consequently, in the treatment of Crohn's disease (CD). The aim of this study is to show that the evaluation of lymphatic anomaly might be a useful tool in the recognition of the pathological involvement of the intestinal wall in CD. MATERIAL AND METHODS: Fourteen patients with CD who underwent surgical treatment for distal ileum critical stenosis were prospectively evaluated. During surgery, 0.05 to 0.1 mL of Patent Blue V was injected into the subserosal layer of the antimesenteric edge of ileum and colon. The intestinal section was performed just beneath the outflow of the vital dye where it seemed to be normal (≤2 minutes), as a index of healthy intestinal wall. A comparison between the lymphatic alterations and the macroscopic aspects was performed. RESULTS: Out of 14 patients, 13 were electively operated on, whereas 1 was treated in emergency. In 8 patients (57%), laparoscopic approach was chosen in the first instance. One patient needed laparotomic conversion. When comparing the Patent Blue V outflow time with the macroscopic and microscopic evidence of CD, we found an absolute integrity of the intestinal wall with an outflow ≤2 minutes. Mean follow-up was 110 months with a recurrence rate of 14%. CONCLUSION: We can conclude that this method may be of utility to distinguish between normal and diseased intestine in CD. The possible consequences in postsurgical recurrences of this evidence are critical.

State of the Art and Future of Stem Cell Therapy in Ischemic Stroke: Why Don't We Focus on Their Administration?

Stroke is one of the leading causes of death and disability worldwide, so there is an urgent need to find a therapy for the tragic outcomes of this cerebrovascular disease. Stem cells appeared to be a good solution for many conditions, so different experiments were made to establish stem cells as a feasible therapy for stroke. The aim of this review is to analyze the state of the art of stem cell therapy for stroke and if the route of administration could represent a valid adjusting point for ameliorating the therapy's outcome. To obtain this, we searched the scientific literature of the last 10 years for relevant in vitro and in vivo evidence regarding stem cells' potential in stroke therapy. In vitro evidence points to hypoxia, among the preconditioning strategies, as the most used and probably efficient method to enhance cells qualities, while in vivo results raise the question if it is the type of cells or how they are administrated which can make the difference in terms of efficiency. Unfortunately, despite the number of clinical trials, only a few were successfully concluded, demonstrating how urgent the necessity is to translate pre-clinical results into clinics. Since any type of stem cell seems suitable for therapy, the chosen route of administration corresponds to different engraftment rates, distribution and efficiency in terms of the beneficial effects of stem cells. Intravenous administration was widely used for delivering stem cells into the human body, but recently intranasal administration has given promising results in vivo. It allows stem cells to efficiently reach the brain that was precluded to intravenous administration, so it is worth further investigation.