Ultrasound-targeted microbubble destruction improves the suppression and magnetic resonance imaging of pancreatic cancer with polyethyleneimine nanogels.

The chemoresistance of pancreatic cancer tumors urgently needs to be addressed. Pancreatic cancer is characterized by an abundant stroma, with significant fibrous connective tissue formation that encapsulates the tumor parenchyma and forms an interstitial microenvironment. Pancreatic stellate cells (PSCs) play a crucial role in this microenvironment and specially secrete periosteal protein (periostin), which can promote tumor growth, metastasis, and chemoresistance. Therefore, periostin has become a specific target of chemotherapy resistance intervention methods. The proposed polyethyleneimine (PEI) nanogels have multiple modification and efficient drug-loading properties. Additionally, ultrasound-targeted microbubble destruction (UTMD) supports the breakdown of the tough interstitial barrier of pancreatic cancer. A small interfering RNA (siRNA) can be used to downregulated the periostin gene, while sustained release of gemcitabine can promote killing of tumor cells. This method achieves a combination of gene silencing and chemotherapy. The imaging effect can be evaluated using magnetic resonance imaging (MRI). The ultimate goal of this work is to support individualized and effective therapeutic methods and help develop new strategies for pancreatic cancer treatment.

Ultrasound-Targeted Microbubble Destruction Increases BBB Permeability and Promotes Stem Cell-Induced Regeneration of Stroke by Downregulating MMP8.

The objective of this study was to evaluate the feasibility, safety, and effectiveness of intravenous stem cell delivery utilizing ultrasound-targeted microbubble destruction (UTMD) in a rat model of middle cerebral artery occlusion (MCAO), while investigating the underlying mechanisms. Acute cerebral infarction (ACI) was induced surgically in adult rats to create the MCAO rat model. Intravenous injection of SonoVue microbubbles and bone marrow-derived mesenchymal stem cells (BMSC) was performed concurrently, with or without ultrasound targeting the stroke. The animals were divided into four groups: sham-operated group, ACI-MCAO rats treated with phosphate-buffered saline (ACI+PBS), rats receiving intravenous delivery of BMSC expressing green fluorescent protein (GFP-BMSC; ACI+BMSC), and rats receiving intravenous GFP-BMSC with simultaneous UTMD exposure (ACI+BMSC+UTMD). The efficacy of the treatments was assessed by evaluating the animals' neurological function using the Longa score and examining histopathological changes such as cerebral infarct volume, cerebral edema, and cell apoptosis. A rat cytokine array was utilized to identify the potential cytokines that may be responsible for the therapeutic effect of UTMD-mediated BMSC treatment. Optimal UTMD parameters resulted in an increase in blood-brain barrier (BBB) permeability after 30 min, which returned to baseline 72 h later without causing any residual injury. UTMD application significantly increased the homing of intravenously delivered BMSC, resulting in a 2.2-fold increase in GFP-BMSC cell count on day 3 and a 2.6-fold increase on day 7 compared with intravenous delivery alone. This effect persisted for up to 6 weeks after injection. Intravenous BMSC delivery significantly reduced the volume of cerebral infarct and decreased cerebral edema, leading to a lower Longa score. Furthermore, this effect was further enhanced by UTMD. Acute cerebral infarction induced by MCAO led to elevated matrix metalloproteinase 8 (MMP8) levels in the cerebrospinal fluid, which were significantly reduced following UTMD-mediated BMSC treatment. Ultrasound-targeted microbubble destruction facilitates the migration and homing of BMSC into the brain, possibly by transiently increasing blood-brain barrier (BBB) permeability, thereby improving therapeutic outcomes in an ACI rat model. The observed effect may be partly attributed to modulation of MMP8 levels.Advances in knowledge: UTMD-mediated intravenously delivered BMSC transplantation led to a significant increase in cell homing and reduction of MMP8 levels, resulting in increased therapeutic effect in an acute ischemic cerebral infarction model.

Association between urinary oxytocin secretion and natriuresis after transsphenoidal pituitary surgery.

OBJECTIVE: Oxytocin (OXT) secretion has been shown to be abnormally elevated in patients who develop syndrome of inappropriate secretion of antidiuretic hormone (SIADH)-related hyponatremia after transsphenoidal pituitary surgery (TPS). While OXT was previously reported to increase natriuresis in the kidney, a potential role for this hormone in postoperative sodium balance and dysnatremias has not been studied. The objective of this study was to analyze the correlation between patients' urinary output of OXT and natremia and natriuresis after TPS. METHODS: The authors measured and correlated the urinary output of OXT with natriuresis and natremia in 20 consecutive patients who underwent TPS. RESULTS: The ratio of urinary secretion of OXT between days 1 and 4 showed a strong, significant correlation with patient natriuresis at day 7 after pituitary surgery. Concomitantly, patient natremia showed a moderate, inverted correlation with OXT secretion in the urine. CONCLUSIONS: Together, these results show for the first time that urinary OXT secretion correlates with patient natriuresis and natremia after pituitary surgery. This observation suggests a notable role for this hormone in sodium balance.

Application of virtual reality in neurosurgery: Patient missing. A systematic review.

Virtual reality (VR) technology had its earliest developments in the 1970s in the U.S. Air Force and has since evolved into a budding area of scientific research with many practical medical purposes. VR shows a high potential to benefit to learners and trainees and improve surgery through enhanced preoperative planning and efficiency in the operating room. Neurosurgery is a field of medicine in which VR has been accepted early on as a useful and promising tool for neuro-navigation planning. Through recent technological developments, VR further increased its level of immersion, accessibility and intuitive use for surgeons and students and now reveals a therapeutic potential for patients. In this paper, we systematically reviewed the neurosurgery literature regarding the use of VR as an assistance for surgery or a tool centered on patients' care. A literature search conducted according to PRISMA guidelines resulted in the screening of 125 abstracts and final inclusion of 100 original publications reviewed. The review shows that neurosurgeons are now relatively familiar with VR technologies (N = 95 articles) for their training and practice. VR technologies are useful for education, pain management and rehabilitation in neurosurgical patients. Nevertheless, the current patient-oriented use of VR remains limited (N = 5 articles). Successful surgery does not only depend on the surgeon's skills and preparation, but also on patients' education, comfort, empowerment and care. Therefore further clinical research is needed to promote the direct use of VR technologies by patients in neurosurgery.

Neuropsychological Outcomes after Surgery for Olfactory Groove Meningiomas.

BACKGROUND: In recent years, several studies have reported abnormal pre- and postoperative neuropsychological functioning in patients with meningiomas located in the prefrontal cortex (notably the ventromedial region). In the case of olfactory groove meningiomas, the tumor is in direct contact with the inferior aspect of the prefrontal cortex, a cortical region with crucial roles in decision-making, cognition and memory functions, potentially negatively impacting neuropsychological functions. MATERIALS AND METHODS: We retrospectively compared pre- and post-operative neuropsychological testing of 17 patients undergoing surgical removal of olfactory groove meningiomas in our institution between January 2013 and December 2018. Neuropsychological results were obtained from the patients' medical history and normalized as z-scores of their respective cognitive functions. RESULTS: Assessment of cognitive follow-up showed an important heterogeneity among patients. Pre-operative cognitive impairment was observed in most patients, particularly in cognitive flexibility (mean z-score: -1.35). Immediate post-operative cognitive status showed an overall impairment in all domains of cognition, significant for the domains of attention (p = 0.0273) and flexibility (p = 0.0234) and almost significant for the domain of language (p = 0.0547). The late follow-up at one year showed a trend towards general improvement, although attention and flexibility remained impaired. DISCUSSION: Olfactory groove meningiomas impact pre-frontal cortex cognitive functions, particularly in the domain of cognitive flexibility. After an initial postoperative worsening, patients tended to improve in most aspects after one year, aside from cognitive flexibility and attention.

Endogenous erythropoietin signaling regulates migration and laminar positioning of upper-layer neurons in the developing neocortex.

Erythropoietin (EPO), the hypoxia-inducible hematopoietic hormone, has well-established neuroprotective/neurotrophic roles in the developing central nervous system and the therapeutic potential of EPO has been widely explored in clinical studies for the treatment of perinatal hypoxic brain lesion, as well as prematurity. Here, we reveal that both EPO and Epo receptor (EPOR) are expressed in the developing rat somatosensory cortex during radial migration and laminar positioning of granular and supragranular neurons. Experimental deregulation of EPO signaling using genetic approaches results in aberrant migration, as well as permanent neuronal misplacement leading to abnormal network activity and protracted sensory behavioral deficits. We identify ERK as the downstream effector of the EPO signaling pathway for neuronal migration. These findings reveal a crucial role for endogenous EPO signaling in neuronal migration, and offer important insights for understanding how the temporary deregulation of EPO could result in migration defects that lead to abnormal behavior in the adult.

Long-term Production of Glycogen and Hepatic-Derived, Cell-Invasion-Promoting Chemokines by Ultrasound-Driven Hepatic-Differentiated Human Bone Marrow Mesenchymal Stem Cells.

The current treatment for liver failure is restricted to surgical liver transplantation, which is technically complicated, limited by the shortage of available organs and presents major risks to the patient. Bone marrow mesenchymal stem cells (BMSCs) represent promising sources of hepatocyte-like cells for cell transplantation treatment. However, a safe and efficient induction method for their differentiation remains to be defined. Here we further optimized an effective technique by combining high-dose treatment with hepatocyte growth factor (HGF) and ultrasound stimulation. The optimized ultrasound parameter (1.0 W/cm2 intensity, 1 MHz frequency, 20% duty cycle, 100 Hz pulse repetition frequency, 60-s irradiation duration, triple times in three days) combined with different HGF doses (10, 20 and 50 ng/ml) was used to treat BMSCs. The results showed that the specific hepatic markers, including α-fetoprotein (αFP/AFP), cytokeratin 18 (CK18), albumin (ALB) and glycogen, were increased in a dose-dependent manner. Their concentration was then further increased when ultrasound irradiation was administered (P < 0.05), as indicated by PCR, Western blot and immunofluorescence staining as well as a glycogen synthesis test. Furthermore, analysis of the hepatocyte-derived chemokines showed elevated stromal cell-derived factor 1alpha (SDF-1α) and C-X-C chemokine receptor type 4 (CXCR4) after HGF treatment. Again, concentrations of those chemokines were further increased by ultrasound radiation (P < 0.05). The observed increased effect was sustained for 21 days. To summarize, we further defined the optimal combination of HGF and ultrasound treatment to increase the differentiation and chemotaxis of BMSCs in a safe, sustained and efficient manner. These findings provide a new perspective for stem cell orientation in the field of tissue engineering.

Loss of neuromonitoring signal during bilateral thyroidectomy: no systematic change in operative strategy according to a survey of the French Association of Endocrine Surgeons (AFCE).

BACKGROUND: Total thyroidectomy presents a risk of bilateral vocal cord paralysis, which can lead to compromised airway. Visual Recurrent Laryngeal Nerve (RLN) identification significantly decreases this risk of RLN lesion. Yet, an anatomically intact nerve is not always functional. Intraoperative neuromonitoring (IONM) allows to test in real time the function of the RLN. In case of loss of signal (LOS) on the first operated side, some authors recommend to stop the intervention. The purpose of this study was to characterize the operative strategy of the French-speaking surgeons in case of LOS on the first side in planned bilateral thyroidectomies. METHODS: An online questionnaire was sent to the surgeons of the French Association of Endocrine Surgeons (AFCE). RESULTS: We collected 69 responses (response rate: 42%). Forty-six surgeons (66%) used IONM. After a signal loss, 22% (N = 10) stopped the operation in all cases, 24% (N = 11) continued the operation in case of malignant disease and stopped in cases of benign disease, and 54% (N = 25) continued the operation contralaterally. CONCLUSIONS: The majority of surgeons continued the operation contralaterally as originally planned despite a loss of IONM signal at the end of the first side.