Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID.

SARS-CoV-2, the etiological agent of COVID-19, is devoid of any metabolic capacity; therefore, it is critical for the viral pathogen to hijack host cellular metabolic machinery for its replication and propagation. This single-stranded RNA virus with a 29.9 kb genome encodes 14 open reading frames (ORFs) and initiates a plethora of virus-host protein-protein interactions in the human body. These extensive viral protein interactions with host-specific cellular targets could trigger severe human metabolic reprogramming/dysregulation (HMRD), a rewiring of sugar-, amino acid-, lipid-, and nucleotide-metabolism(s), as well as altered or impaired bioenergetics, immune dysfunction, and redox imbalance in the body. In the infectious process, the viral pathogen hijacks two major human receptors, angiotensin-converting enzyme (ACE)-2 and/or neuropilin (NRP)-1, for initial adhesion to cell surface; then utilizes two major host proteases, TMPRSS2 and/or furin, to gain cellular entry; and finally employs an endosomal enzyme, cathepsin L (CTSL) for fusogenic release of its viral genome. The virus-induced HMRD results in 5 possible infectious outcomes: asymptomatic, mild, moderate, severe to fatal episodes; while the symptomatic acute COVID-19 condition could manifest into 3 clinical phases: (i) hypoxia and hypoxemia (Warburg effect), (ii) hyperferritinemia ('cytokine storm'), and (iii) thrombocytosis (coagulopathy). The mean incubation period for COVID-19 onset was estimated to be 5.1 days, and most cases develop symptoms after 14 days. The mean viral clearance times were 24, 30, and 39 days for acute, severe, and ICU-admitted COVID-19 patients, respectively. However, about 25-70% of virus-free COVID-19 survivors continue to sustain virus-induced HMRD and exhibit a wide range of symptoms that are persistent, exacerbated, or new 'onset' clinical incidents, collectively termed as post-acute sequelae of COVID-19 (PASC) or long COVID. PASC patients experience several debilitating clinical condition(s) with >200 different and overlapping symptoms that may last for weeks to months. Chronic PASC is a cumulative outcome of at least 10 different HMRD-related pathophysiological mechanisms involving both virus-derived virulence factors and a multitude of innate host responses. Based on HMRD and virus-free clinical impairments of different human organs/systems, PASC patients can be categorized into 4 different clusters or sub-phenotypes: sub-phenotype-1 (33.8%) with cardiac and renal manifestations; sub-phenotype-2 (32.8%) with respiratory, sleep and anxiety disorders; sub-phenotype-3 (23.4%) with skeleto-muscular and nervous disorders; and sub-phenotype-4 (10.1%) with digestive and pulmonary dysfunctions. This narrative review elucidates the effects of viral hijack on host cellular machinery during SARS-CoV-2 infection, ensuing detrimental effect(s) of virus-induced HMRD on human metabolism, consequential symptomatic clinical implications, and damage to multiple organ systems; as well as chronic pathophysiological sequelae in virus-free PASC patients. We have also provided a few evidence-based, human randomized controlled trial (RCT)-tested, precision nutrients to reset HMRD for health recovery of PASC patients.

Effect of a retinoic acid analogue on BMP-driven pluripotent stem cell chondrogenesis.

Osteoarthritis is the most common degenerative joint condition, leading to articular cartilage (AC) degradation, chronic pain and immobility. The lack of appropriate therapies that provide tissue restoration combined with the limited lifespan of joint-replacement implants indicate the need for alternative AC regeneration strategies. Differentiation of human pluripotent stem cells (hPSCs) into AC progenitors may provide a long-term regenerative solution but is still limited due to the continued reliance upon growth factors to recapitulate developmental signalling processes. Recently, TTNPB, a small molecule activator of retinoic acid receptors (RARs), has been shown to be sufficient to guide mesodermal specification and early chondrogenesis of hPSCs. Here, we modified our previous differentiation protocol, by supplementing cells with TTNPB and administering BMP2 at specific times to enhance early development (referred to as the RAPID-E protocol). Transcriptomic analyses indicated that activation of RAR signalling significantly upregulated genes related to limb and embryonic skeletal development in the early stages of the protocol and upregulated genes related to AC development in later stages. Chondroprogenitors obtained from RAPID-E could generate cartilaginous pellets that expressed AC-related matrix proteins such as Lubricin, Aggrecan, and Collagen II, but additionally expressed Collagen X, indicative of hypertrophy. This protocol could lay the foundations for cell therapy strategies for osteoarthritis and improve the understanding of AC development in humans.

Eagle syndrome: An updated review.

Background: This work aims to review the current literature and our experience on vascular Eagle syndrome (ES) that can present misleading clinical presentations and better understand the possible therapeutic strategies. Methods: We reviewed the existing literature on PubMed from January 1, 2017, to December 31, 2022, including the sequential keywords "vascular AND Eagle syndrome," "vascular AND styloid syndrome," "vascular AND elongated styloid process," "vascular AND stylocarotid syndrome," and "Eagle syndrome AND carotid artery dissection." Results: 38 vascular ES cases, including our experience, were analyzed. The most frequent clinical onset was hemiparesis (n 21, 57%), but other regular clinical presentations were aphasia, loss of consciousness, amaurosis, headache, or a combination of the latter. Massive oral bleeding was reported only once in the literature before our case. Twelve patients were treated with only antiplatelet therapy, either single or double. Nine patients were treated with anticoagulation therapy only. In 14 patients, a carotid artery stent was used, associated with anticoagulation or antiplatelet therapy. In 17 cases, a styloid process (SP) resection was performed. Conclusion: ES has many clinical presentations, and carotid artery dissection resulting in oral bleeding seems rare. Literature results and our experience make us believe that when dealing with vascular ES, the best treatment strategy is endovascular internal carotid artery stenting with antiplatelet therapy, followed by surgical removal of the elongated SP to prevent stent fracture.

Optogenetic manipulation of BMP signaling to drive chondrogenic differentiation of hPSCs.

Optogenetics is a rapidly advancing technology combining photochemical, optical, and synthetic biology to control cellular behavior. Together, sensitive light-responsive optogenetic tools and human pluripotent stem cell differentiation models have the potential to fine-tune differentiation and unpick the processes by which cell specification and tissue patterning are controlled by morphogens. We used an optogenetic bone morphogenetic protein (BMP) signaling system (optoBMP) to drive chondrogenic differentiation of human embryonic stem cells (hESCs). We engineered light-sensitive hESCs through CRISPR-Cas9-mediated integration of the optoBMP system into the AAVS1 locus. The activation of optoBMP with blue light, in lieu of BMP growth factors, resulted in the activation of BMP signaling mechanisms and upregulation of a chondrogenic phenotype, with significant transcriptional differences compared to cells in the dark. Furthermore, cells differentiated with light could form chondrogenic pellets consisting of a hyaline-like cartilaginous matrix. Our findings indicate the applicability of optogenetics for understanding human development and tissue engineering.

Directed differentiation of hPSCs through a simplified lateral plate mesoderm protocol for generation of articular cartilage progenitors.

Developmentally, the articular joints are derived from lateral plate (LP) mesoderm. However, no study has produced both LP derived prechondrocytes and preosteoblasts from human pluripotent stem cells (hPSC) through a common progenitor in a chemically defined manner. Differentiation of hPSCs through the authentic route, via an LP-osteochondral progenitor (OCP), may aid understanding of human cartilage development and the generation of effective cell therapies for osteoarthritis. We refined our existing chondrogenic protocol, incorporating knowledge from development and other studies to produce a LP-OCP from which prechondrocyte- and preosteoblast-like cells can be generated. Results show the formation of an OCP, which can be further driven to prechondrocytes and preosteoblasts. Prechondrocytes cultured in pellets produced cartilage like matrix with lacunae and superficial flattened cells expressing lubricin. Additionally, preosteoblasts were able to generate a mineralised structure. This protocol can therefore be used to investigate further cartilage development and in the development of joint cartilage for potential treatments.

Modified percutaneous biopsy of the spine: improvement of the technique.

PURPOSE: Biopsy of the spine can be performed by open surgery or percutaneous needle sampling. The first has the highest diagnostic yield while the second is a less invasive procedure with lower rate of complications and shorter hospitalization time. We described a modified technique of percutaneous biopsy using semi-rigid grasping forceps that may offer the advantages of both, open and minimally invasive surgery. METHODS: Thirty consecutive patients with spinal lesions requiring biopsy were admitted to Neurosurgical Unit of Belcolle Hospital (Viterbo, Italy) from January 2017 to September 2021. There was a suspicion of spondylodiscitis in 25 cases and of tumor in 5 cases. Percutanous trans-pedicular spine biopsy has been performed using this new semi-rigid grasping forceps. Combining the opening width, jaw length and full 360° rotation, the device allows a wide and precise sampling. RESULTS: Sampling was sufficient in all cases (100%); tumors was observed in 5 cases (16.7%%) with a percentage of definitive histopathologic diagnosis of 100% (n = 5); among the remaining patients histological examination yielded a diagnosis of spinal infection in 25 cases (100%), and microbiologic culture provided an aetiologic diagnosis in 23 cases (92%). All procedures were well tolerated, and no postoperative complications were observed. Levels involved included: thoracic (T5-T9) in 8 cases, thoracolumbar junction (T10-L2) in 12 cases and lumbar (L3-L5) in 10 cases. CONCLUSIONS: Percutaneous biopsy with the semi-rigid grasping forceps is a safe and effective procedure that can be used for diagnosis of both infectious and tumor lesions of the spine. It allows to obtain a larger specimen volume and to use a multidirectional trajectory for sampling, resulting in a minimally invasive technique with strong ability to yield etiologic diagnosis.

Deep brain stimulation for Parkinson's disease in practice: results of the survey by the Italian Neurosurgery Society.

BACKGROUND: Deep brain stimulation (DBS) is a safe and effective treatment for patients with advanced Parkinson's disease (PD) and many neurosurgical centers in Italy have a DBS program. Considering the prevalence of PD and criteria for DBS implantation, about 3200-10,350 PD patients may benefit from DBS in Italy. The global management of patients underwent DBS is complex and it can be supposed that many differences exist between centers in clinical practice. The Italian Neurosurgery Society (SINch) designed this survey to investigate the state of the art of DBS for PD in Italy. METHODS: A 26-item closed-ended question survey was designed and sanded by email at all Italian Neurosurgery centers. The main topic investigated was DBS teams, anatomical target selection, surgical procedure, neuroimaging, intraoperative target localization, DBS device and patients' follow-up. RESULTS: A total of 23 neurosurgery centers completed the survey. There are mainly low-to medium-volume centers (<20 annual DBS procedures) with dedicated DBS teams. The principal anatomical target used is subthalamic nucleus (STN) and, relative to the surgical technique, it emerges that in Italy DBS are bilaterally implanted in a single-step session with awake anesthesia and with frame-based technique. Final leads positioning is defined by microelectrode recordings (MER) and microstimulation (MS), with limited role of intraoperative neuroimaging (MRI and O-Arm). The stimulation is started at 15 or 30 days from procedure. CONCLUSIONS: Many centers of neurosurgery in Italy have a well-established DBS program for patients with advanced PD and some practical differences in technique between centers exist. Further investigation is needed to investigate specific criteria for selecting one technique over another.

Fronto-orbito-zygomatic (FOZ) approach for infratemporal fossa lesions extending to middle cranial fossa: our experience and review of literature.

AIM OF THE STUDY: Tumours of the infratemporal fossa (ITF) are rare and include primary tumours, contiguity lesions and metastases. Surgical resection is the gold standard. The fronto-orbito-zygomatic (FOZ) approach is commonly used in order to obtain safe access to the lateral skull base and ITF to resect intra- and extra-cranial tumours. We here describe our series of ITF lesions extending to the middle cranial fossa and/or orbit, treated by single- or two piece FOZ. MATERIAL AND METHODS: All cases of single- or two-piece FOZ approach for an infratemporal fossa lesion extending to the middle cranial fossa operated at our Institution from January 2014 to January 2018 were retrospectively reviewed. The follow-up was for a minimum of four months and a maximum of 60 months. The inclusion criteria were lesions involving the ITF with an extension to the middle cranial fossa and/or orbit. Baseline characteristics of patients, tumour localisation, tumour extension, diffusion route, histology, extent of tumour resection, postoperative treatment, and post-operative complications were evaluated. RESULTS: Nine patients underwent a surgical procedure with a FOZ approach, two of them with a single-piece approach and the remainder with a two-piece one. All patients had an ITF localisation. Gross total removal (GTR) was achieved in 7/9 patients. Only one patient, with non-total removal (NTR), underwent radiotherapy. CONCLUSIONS: For the treatment of ITF fossa tumours extending to the orbit and or middle cranial fossa, we believe that both FOZ techniques are effective and allow a good medial extension toward the cavernous sinus and parasellar region. But a two-piece craniotomy may ensure a more medial extension and a wider angle of work compared to a one-piece craniotomy.

Developmental principles informing human pluripotent stem cell differentiation to cartilage and bone.

Human pluripotent stem cells can differentiate into any cell type given appropriate signals and hence have been used to research early human development of many tissues and diseases. Here, we review the major biological factors that regulate cartilage and bone development through the three main routes of neural crest, lateral plate mesoderm and paraxial mesoderm. We examine how these routes have been used in differentiation protocols that replicate skeletal development using human pluripotent stem cells and how these methods have been refined and improved over time. Finally, we discuss how pluripotent stem cells can be employed to understand human skeletal genetic diseases with a developmental origin and phenotype, and how developmental protocols have been applied to gain a better understanding of these conditions.

Clinical Outcome of Patients Over 90 Years of Age Treated for Chronic Subdural Hematoma.

OBJECTIVE: Chronic subdural hematoma (CSDH) is one of the most common pathology in daily neurosurgical practice and incidence increases with age. The aim of this study was to evaluate the prognostic factors and surgical outcome of CSDH in patients aging over 90 years compared with a control group of patients aging under 90 years. METHODS: This study reviewed 25 patients with CSDH aged over 90 years of age treated in our department. This group was compared with a younger group of 25 patients aged below their eighties. At admission past medical history was recorded concerning comorbidities (hypertension, dementia, ictus cerebri, diabetes, and heart failure or attack). History of alcohol abuse, anticoagulant and antiplatelet therapy, head trauma and seizures were analyzed. Standard neurological examination and Markwalder score at admission, 48 hours after surgery and 1-6 months follow-up, radiologic data including location and CSDH maximum thickness were also evaluated. RESULTS: Their mean age was 92.8 years and the median was 92.4 years (range, 90-100 years). In older group, the Markwalder evaluation at one month documented the complete recovery of 24 patients out of 25 without statistical difference with the younger group. This data was confirmed at 6-month follow-up. One patient died from cardiovascular failure 20 days after surgery. The presence of comorbidities, risk factors (antiplatelet therapy, anticoagulant therapy, history of alcohol abuse, and head trauma), preoperative symptoms, mono or bilateral CSDH, maximum thickness of hematoma, surgical time and recurrence were similar and statistically not significant in both groups. CONCLUSION: In this study, we demonstrate that surgery for very old patients above 90 years of age affected by CSDH is safe and allows complete recovery. Comparing two groups of patients above and under 90 years old we found that complication rate and recovery were similar in both groups.

Pluripotent stem cells for skeletal tissue engineering.

Here, we review the use of human pluripotent stem cells for skeletal tissue engineering. A number of approaches have been used for generating cartilage and bone from both human embryonic stem cells and induced pluripotent stem cells. These range from protocols relying on intrinsic cell interactions and signals from co-cultured cells to those attempting to recapitulate the series of steps occurring during mammalian skeletal development. The importance of generating authentic tissues rather than just differentiated cells is emphasized and enabling technologies for doing this are reported. We also review the different methods for characterization of skeletal cells and constructs at the tissue and single-cell level, and indicate newer resources not yet fully utilized in this field. There have been many challenges in this research area but the technologies to overcome these are beginning to appear, often adopted from related fields. This makes it more likely that cost-effective and efficacious human pluripotent stem cell-engineered constructs may become available for skeletal repair in the near future.

Review of laminoplasty versus laminectomy in the surgical management of cervical spondylotic myelopathy.

BACKGROUND: We reviewed the literature comparing the indications/efficacy of laminectomy (LA) with or without fusion versus laminoplasty (LP) in the treatment of cervical spondylotic myelopathy (CSM). METHODS: We identified 14 studies in PubMed/Medline to include in our analysis. Outcomes were assessed utilizing the Japanese Orthopaedic Association (JOA) score, visual analog scale (VAS), Neck Disability Index, and Nurick scale. Variables studied included ossification of the posterior longitudinal ligament (OPLL), cervical range of motion (ROM), the C2-C7 sagittal Cobb angle, the Ishihara index, and the Hirabayashi scale. Patients with cervical trauma/fracture, infection, or tumor were excluded from the study. RESULTS: In these 14 studies, there were no significant differences between LA and LP groups in terms of preoperative versus postoperative: JOA scores (e.g., including the improvement rate), VAS scores, and ROM. However, the LA patients demonstrated greater postoperative cervical lordosis versus those in the LP group. CONCLUSION: At present, there are no guidelines for choosing LA versus LP for treating CSM. Factors that should be considered when choosing one procedure over the other should include the patients' preoperative clinical status, the type of CSM, the pathological extent of OPLL, and whether there is a sufficient cervical lordotic curvature.

Clinical and radiological risk factors of autograft cranioplasty resorption after decompressive craniectomy for traumatic brain injury.

OBJECTIVE: The repositioning of an autologous bone flap after decompressive craniectomy (DC) for traumatic intracranial hypertension remains the first-line treatment for cranial reconstruction. Aseptic autologous bone flap resorption (BFR) is the most frequent complication. The identification of possible predictive parameters for BFR would help to improve the management of these patients. PATIENTS AND METHODS: Three hundred and nine patients undergoing autologous bone flap repositioning after previous DC for TBI between September 2003 and September 2017 were included in the study. RESULTS: BFR was identified in 76 (24,59 %) of the 309 patients undergoing autologous CP. Age of ≤ 45 years and CP bone fragmentation were seen to be significant independent risk factors for BFR (p =  0.001 and p =  0.018, respectively) using multivariate logistic regression analysis. Of the radiologic predictors, CP size and the gap between CP and the skull defect were independently associated with BFR (p =  0.034 and p =  0.0003, respectively). The Youden index and ROC curve analysis were used to estimate the cut-off values for the continuous parameters and determine the sensitivity and specificity of the radiologic risk factors. The cut-off value for these two factors was found to be 114,98 cm2 and ≥ 578,5 mm2, respectively. The area under the ROC curve was 0.627 for bone flap size and 0.758 for the DC-CP gap. The DC-CP gap had greater sensitivity and specificity as a predictor of BFR, compared to bone flap size (p = 0.079 and p = ≤ 0.001, respectively). CONCLUSIONS: In this large cohort of patients with autologous cranioplasty, younger age, fragmented autologous bone flap and a wide gap between CP and cranial defect were predictive of bone flap resorption.

Laminectomy versus open-door laminoplasty for cervical spondylotic myelopathy: A clinical outcome analysis.

BACKGROUND: Cervical spondylotic myelopathy (CSM) is one of the most common diseases in the geriatric population. Decompressive laminectomy or laminoplasty is the predominant surgical procedure of choice, but there remains debate as to which procedure is optimal for managing CSM. METHODS: Here, we retrospectively analyzed 64 patients with CSM undergoing laminectomy (39 patients) versus laminoplasty (25 patients). The data were collected included respective Japanese orthopedic association (JOA) scores, Nurick grades, and Visual analog scale (VAS) values preoperatively versus 12 months postoperatively. RESULTS: The JOA score after 1 month improved in both groups utilizing laminectomy or laminoplasty. However, at 12 postoperative months, the JOA scores and Nurick grades showed greater improvement following laminoplasty, despite no differences in postoperative pain and complication rates. CONCLUSION: Patients with cervical spondylotic myelopathy undergoing laminoplasty (25 patients) showed better 12-month postoperative outcomes (JOA scores and Nurick grades) versus those having laminectomies (39 patients).

The relationship between preoperative predictive factors for clinical outcome in patients operated for lumbar spinal stenosis by decompressive laminectomy.

BACKGROUND: Our hypothesis was that by identifying certain preoperative predictive factors, we could favorably impact clinical outcomes in patients undergoing decompressive surgery for lumbar spinal stenosis (LSS). METHODS: In this retrospective study, there were 65 patients (2016-2018) with symptomatic LSS who underwent decompressive laminectomy without fusion. Their clinical outcomes were assessed utilizing the Oswestry Disability Index (ODI). Multiple preoperative variables were studied to determine which ones would help predict improved outcomes: gender, age, body mass index (BMI), general/neurological examination, smoking, and drug therapies (anxiolytics and/or antidepressants). RESULTS: All patients demonstrated statistically significant improvement on the ODI. Multivariate analysis revealed that those with higher preoperative BMI had significantly lower ODI on 1-year follow-up examinations, reflecting poorer outcomes. Postoperatively, 44 patients (67%) exhibited lower utilization of anxiolytic medications, 52 patients (80%) showed reduced use of antidepressant drugs, and pain medications utilization was reduced in 33 patients (50%). CONCLUSION: Decompressive laminectomy without fusion effectively managed LSS. It reduced patients' use of pain, anxiety, and antidepressant medications. In addition, we found that increased preoperative BMIs contributed to poorer postoperative outcomes (e.g., ODI values).

Ultra-early surgery in complete cervical spinal cord injury improves neurological recovery: A single-center retrospective study.

BACKGROUND: This study evaluated how the neurological outcome in patients operated on cervical spinal cord injury (SCI) was positively influenced by ultra-early surgery (UES). METHODS: Between 2010 and 2017, 81 patients with traumatic cervical SCI were assigned to the UES group (<12 h after injury; UES) and ES group (surgery between 12 and 48 h after injury; ES). Additional variables evaluated for the two groups included; age, sex, comorbidities charlson comorbidity index (CCI), level of trauma, type of fracture, preoperative and ASIA scores, pre- and post-operative neuroradiological examinations, surgical approaches, and complications. RESULTS: Forty-seven of 81 (58.02%) patients exhibited improved neurological function 12 months postoperatively; better outcomes were observed in the UES (29 of 40 [72.5%]) versus ES groups (18 of 41 [43.9%]) (P = 0,009). For the 26 patients with complete cervical SCI (ASIA A), ultra-early surgical decompression was associated with significantly greater neurological improvement versus ES (61.53% vs. 7.69%; P = 0.003). Further, more neurological improvement correlated with the younger age, better ASIA grade at admission, and ultra-early surgical timing (< 12 h) both in the univariate and multivariate analysis (P = 0.037, P = 0.017, and P = 0.005, respectively), while CCI was correlated with improvement only in the univariate analysis (P = 0.005). CONCLUSION: Ultra-early surgical timing in SCI patients appeared to be the most important factor determining the extent of postoperative neurological improvement, particularly regarding motor function recovery.

Energy Potential of Animal Waste in the State of Paraná (Brazil)

Abstract Animal biomass is a source of energy commonly discarded without or with low utilization, but its availability draws attention to its reuse [1]. The utilization can be carried out in different ways, varying in terms of generation time and efficiency. The use of biodigestion requires a relatively small area compared to landfills or natural composting, and it provides other materials besides biogas, that can be recycled as fertilizer and has a short residence time of residues [2]. The energy supplied as biogas can be harnessed as heat or electricity in case of conversion. Considering the energy needs of animal husbandry and the ease of reinsertion of energy in the production cycle, the possibility of distributed generation of biogas was studied as a way to complement the rural energy consumption matrix. Poultry farms require heat for chicks [3], dairy production centers require sterilization of used equipment [4] and pig farms require good heating systems to ensure animal weight gain [5]. In this way, the production can take advantage of the heat of the gas without the conversion into electricity, minimizing losses. Creation centers themselves can also generate electricity, eliminating the need for large transmission lines.

Rare case of anterior cervical discectomy and fusion complication in a patient with Zenker's diverticulum.

We present a case of Zenker's diverticulum in a 45-year-old woman, occurred as complication after anterior cervical discectomy and fusion for a cervical spine injury. The oesophageal complication occurred 12 months after vertebral cervical surgery and presenting symptoms were fever, dysphagia and neck pain with evidence of retropharyngeal infection. We performed a posterior cervical stabilisation C3-D1 by screws and rods and a second anterior left cervical approach with anterior plate removing and oesophageal wall break repairing with a sternohyoid muscle patch. Despite pharyngo-oesophageal diverticulum may be a complication of anterior cervical surgery (traction diverticulum), in case of an already present true Zenker's diverticulum, delayed complication may occur without cervical hardware pull-out.

Relationship between the location of the ventricular catheter tip and the ventriculoperitoneal shunt malfunction.

OBJECTIVE: Ventriculoperitoneal (VP) shunt is the most common neurosurgical procedure to treat obstructive and communicating hydrocephalus, but failures are frequent. The most common causes of shunt failure are malpositioning and obstruction of the ventricular catheter by debris or blood clothes. The knowledge of the relationship between ventricular catheter tip position, etiology of hydrocephalus and patient's age with shunt malfunction may be useful to avoid shunt failure. PATIENTS AND METHODS: We retrospectively analyze 89 adult patients affected by obstructive and communicating hydrocephalus operated with Ventriculoperitoneal shunt at our Institute. Patients with evident abdominal shunt malfunction were excluded from this study. Statistical analysis was performed in the group of patients with intracranial catheter malfunction in order to correlate shunt malfunction with the position of the catheter tip in brain ventricles, etiology of hydrocephalus and patient's age. RESULTS: Shunt revision was performed in 26 patients out of 89 and cranial catheter malfunction was documented in 11 patients out of 26. Tip position in Monro foramen, lateral ventricles and third ventricle ("good position") had a lower rate of surgical shunt revision compared to septum pellucidum and wall of lateral ventricle ("bad position") p value = 0,049. No statistical significant association was observed between shunt malfunction and etiology of the hydrocephalus or patient's age. CONCLUSIONS: Ventricular catheter tip position is one the most important factor for shunt function.