Plasma cell-free DNA integrity index and hepatocellular carcinoma treated or not with direct-acting antivirals: A case-control study.

BACKGROUND AND STUDY AIMS: The clinical value of the cell-free DNA (cf-DNA) integrity index as a diagnostic biomarker of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) was investigated and correlated with alpha-fetoprotein (AFP). PATIENTS AND METHODS: This case-control study was conducted on 160 patients with HCV genotype 4-related liver cirrhosis. Group 1 consisted of 80 patients with HCC, including 40 patients naïve to direct-acting antivirals (DAAs) and 40 patients who received DAAs and achieved sustained virological response. Group 2 comprised 80 patients with cirrhosis without HCC. Plasma cf-DNA integrity index using ALU 115 and ALU 247 sequences was assessed using SYBR Green-based real-time polymerase chain reaction (RT-PCR). The cf-DNA integrity index was calculated as the ratio of Q247/Q115 where Q115 and Q247 are the ALU-qPCR results obtained using ALU 115 and ALU 247, respectively. RESULTS: Patients with HCC had significantly lower plasma cf-DNA integrity index than those with liver cirrhosis. No significant difference in the cf-DNA integrity index was observed between patients with HCC who received DAAs and those who did not. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve of 0.965 and 0.886 for detecting HCC using the cf-DNA integrity index and AFP, respectively. The combination of the cf-DNA integrity index and AFP improved the sensitivity from 81.6% to 94.7%, positive predictive value from 93.4% to 94.7%, negative predictive value from 84.4% to 94.9%, and accuracy from 88.4% to 94.8%. CONCLUSION: The cf-DNA integrity index can predict the occurrence of HCV genotype 4-related HCC. No significant difference in the cf-DNA integrity index was observed between patients with HCC who received DAAs and those without previous DAAs. The combination of the cf-DNA integrity index and AFP provides better HCC prediction accuracy.

Outcomes of Mechanical Thrombectomy for Ischemic Stroke in Nonagenarians: A 10-Year Institutional Experience.

BACKGROUND: Nonagenarians have been underrepresented in stroke trials that established endovascular treatment as the standard for acute ischemic stroke (AIS). Evidence remains inconclusive regarding the efficacy of thrombectomy in this population. OBJECTIVES: To report our experience with thrombectomy in nonagenarians with stroke, and to identify predictors of mortality. We further investigated the effects of first-pass reperfusion and the addition of intravenous thrombolysis (IVT) on achieving better outcomes. MATERIALS AND METHODS: Data was collected for consecutively treated patients at three affiliated comprehensive stroke centers from 2010 to 2021. We included patients ≥90 years-old with AIS secondary to large vessel occlusion. Bivariate analyses were performed using the Mann-Whitney U test for continuous variables, and χ2 and Fisher's exact tests, respectively, for nominal and ordinal variables. RESULTS: Thirty-two nonagenarians underwent thrombectomy, of whom 25 (81%) had prestroke mRS ≤2. Thrombectomies were performed using stents (2, 6.7%), aspiration (8, 26.7%), or a combination of both (20, 66.7%). Successful recanalization was achieved in 97%. Procedural complications occurred in 2 (6.3%) and intracranial hemorrhage in 3 (9.4%). Sixteen patients (50%) were discharged home or to rehabilitation, 9 (28.2%) to nursing home or hospice, and 7 (21.9%) died during hospitalization. Only 2 (6%) patients had mRS ≤2 at discharge. No independent predictors of in-hospital mortality were identified, and neither first-pass reperfusion nor the addition of IVT correlated with improvement in clinical outcome. CONCLUSIONS: Although thrombectomy is safe for nonagenarian stroke and can achieve excellent recanalization, high mortality and poor functional status remain high given the advanced age and frailty of this population.

Magnetic Resonance-Guided Laser Interstitial Thermal Therapy for Brainstem Pathologies.

OBJECTIVE: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive and effective treatment option that can potentially treat deep-seated pathologies in cases without safe open surgical corridors. In the present report, we have described our experience using MRgLITT for brainstem pathologies. METHODS: A retrospective medical record review and analysis were conducted for all patients who had undergone MRgLITT for pathologies within or closely surrounding the brainstem between 2011 and 2020. The patients had undergone stereotactic laser placement in the operating suite and were transported to the magnetic resonance imaging suite for laser ablation with real-time monitoring. The demographics, operative parameters, and complications were recorded. RESULTS: A total of 12 patients had undergone MRgLITT for brainstem pathologies. The average age of the patients was 47.6 years (range, 4-75 years). The pathologies included both primary and metastatic intracranial tumors. The average preablation volume of the targets was 2.4 ± 0.50 cm3. The average ablation time was 324.3 ± 60.7 seconds, and the average postablation volume was 2.92 ± 0.53 cm3. One perioperative mortality was directly related to the procedure and 7 patients developed postoperative deficits. Two patients had experienced a recurrence after MRgLITT and opted to undergo additional alternative treatment. CONCLUSIONS: The brainstem represents formidable territory even for minimally invasive procedures. The overall morbidity and mortality has remained high, and the probability of achieving a meaningful outcome must be carefully assessed.

P53 is a risk factor of de-novo hepatitis C-related hepatocellular carcinoma treated with direct-acting antivirals: a case-control study.

BACKGROUND: The mechanisms underlying de-novo hepatocellular carcinoma (HCC) after direct-acting antivirals (DAAs) is still under investigation. This work aims to study P53 and hepatocyte growth factor (HGF) as possible diagnostics of de-novo hepatocellular carcinoma (HCC) following DAAs in comparison to alpha-fetoprotein (AFP). METHOD: This case-control study included 166 patients with liver cirrhosis divided into group-1: patients without HCC (n = 50), group-2: patients with de-novo HCC following DAAs, and achieved sustained virological response (n = 50), and group-3: patients with HCC without DAAs (n = 66). P53 antibody and HGF were determined using a quantitative sandwich enzyme immunoassay technique (Cusabio Co, Houston, USA). RESULTS: Patients with HCC showed significantly higher HGF. Patients with de-novo HCC following DAAs had significantly higher P53 than HCC without DAAs (P < 0.0001). The multiple logistic regression analysis showed that the P53 levels were significantly associated with susceptibility to de-novo HCC (P value = 0.004). The best overall formula was constructed for HCC diagnosis by entering significant markers into the regression model. A three markers model was developed = (1.22 + AFP X 0.002 + HGF X 0.001 + P53 X 0.001). The medians (percentiles) of combined three markers were 1.8 (1.0-2.1) in liver cirrhosis and 2.2 (2.0-2.9) in all HCC (P < 0.00001). The AUC of combined markers was greater than a single marker. The AUC was 0.87 to differentiate HCC from liver cirrhosis; AUC 0.91 to differentiate de-novo HCC after DAAs from liver cirrhosis. CONCLUSION: P53 may serve as a diagnostic marker for de-novo HCC after DAAs therapy. HGF may serve as a diagnostic marker for HCC but not specific for de-novo HCC after DAAs therapy.

Schistosoma mansoni infection and the occurrence, characteristics, and survival of patients with hepatocellular carcinoma: an observational study over a decade.

Schistosoma mansoni infection (SMI) is suspected to be directly and indirectly involved in hepato-carcinogenesis. This study evaluated the association of a previous SMI with hepatocellular carcinoma (HCC) development, patients, tumor characteristics, treatment outcomes, and survival. This observational study included patients with HCC with and without previous SMI who presented to the multidisciplinary HCC clinic, Kasr-Alainy hospital (November 2009 to December 2019). It also included 313 patients with liver cirrhosis without HCC. Clinical and laboratory features of the patients (complete blood count, liver/renal functions , alpha-fetoprotein, and hepatitis B/C status), tumor characteristics (Triphasic CT and/or dynamic MRI), liver stiffness (transient elastography), HCC treatment outcome, and overall survival were studied. This study included 1446 patients with HCC; 688(47.6%) composed group-1, defined by patients having a history of SMI, and 758(52.4%) were in group-2 and without history of SMI. Male sex, smoking, diabetes mellitus, splenomegaly, deteriorated performance status, synthetic liver functions, and platelet count were significantly higher in group-1. The groups did not differ with regard to liver stiffness, tumor characteristics, or the occurrence of post-HCC treatment hepatic decompensation or recurrence. HCC treatment response was better in group-2. Group-1 showed lower sustained virological response to hepatitis C direct-acting antivirals (DAAs) compared with group-2 (60% versus 84.3%, respectively, P = 0.027). Prior SMI was associated with HCC (adjusted odds ratio = 1.589, 95% confidence interval = 1.187-2.127), and it was concluded that it increases the risk of HCC. In addition, it significantly affects the performance status, laboratory characteristics, response to DAAs, and overall survival.

Impact of successful HCV treatment using direct acting antivirals on recurrence of well ablated hepatocellular carcinoma.

BACKGROUND: There are many contradictory studies that dealt with hepatocellular carcinoma (HCC) recurrence rate of well ablated hepatitis C virus (HCV) related HCC. We aim to assess the recurrence rate of previously ablated HCC in patients who received direct acting antiviral (DAA) for their HCV. RESEARCH DESIGN AND METHODS: This is a retrospective data analysis of 523 HCV patients who have a history of successfully ablated HCC and eligible for HCV treatment. Retrieval was done to demographic/clinical data, HCV pretreatment investigations, HCV treatment outcome. Follow up for survival and HCC recurrence was done every 3 months using abdominal ultrasound and alfa-fetoprotein. RESULTS: Mean age was 53.83 years. Sofosbuvir/daclatasvir/ribavirin was the most used regimen (35.4%) with 438 patients (83.7%) achieved sustained virologic response (SVR). The median duration for surveillance was 159 weeks. Hundred and five patients developed recurrent HCC, with a crude recurrence rate of 20.1%. There was no difference between HCV responders and non-responders in crude recurrence rate (p = 0.94) but HCC developed earlier in non-responders (p = <0.01). CONCLUSION: Recurrence of HCC remains a threat in HCV patients even after achieving an SVR. Implementation of long-term surveillance programs is highly recommended.

Role of circulating microRNA-21 and microRNA-215 in the diagnosis of hepatitis C related hepatocellular carcinoma.

INTRODUCTION: Several micro ribonucleic acids (miRNAs) are deregulated in hepatocellular carcinoma (HCC). Others are linked to clinical pathological features of HCC. The goal of this study was to investigate whether miRNA-21 and miRNA-215 gene expression could be used as a non-invasive diagnostic tool to diagnose HCC. METHODOLOGY: The gene expression of mature miRNA -21 and miRNA -215 in serum was analysed retrospectively using singleplex TaqMan two-step stem-loop quantitative real-time reverse-transcription PCR in 40 patients with HCC, 40 with chronic hepatitis C virus (HCV) with cirrhosis and 40 apparently healthy controls. RESULTS: Expression of miRNA -21 was significantly more down regulated in patients with HCC than in those with non-cirrhotic HCV (P = 0.007; odds ratio = 5; 95% confidence interval 1.6-15.4). The receiver operating curve analysis of the ability of miRNA-21 expression to discriminate between HCC and non-cirrhotic HCV revealed an area under the curve of 0.712 with 70% sensitivity and 68% specificity at a cut-off of ≤ 1.4468. Thus, the expression level of miRNA -21 could discriminate HCC from non-cirrhotic HCV. Significant positive correlation was observed between expression levels of microRNA-21 and miRNA -215 (r = 0.783, p < 0.001), but no association was observed between expression level of miR-215 and HCC or chronic HCV (p = 0.474). CONCLUSIONS: MiRNA-21 may be a useful, non-invasive tool for diagnosing HCC. Non-cirrhotic HCV patients have five times the risk of developing HCC when the miRNA -21 level ≤ 1.4468.

Compliance With Preferred Reporting Items for Systematic Review and Meta-Analysis Individual Participant Data Statement for Meta-Analyses Published for Stroke Studies.

Background and Purpose: Individual-participant data meta-analyses (IPD-MA) are powerful evidence synthesis studies which are considered the gold-standard of MA. The quality of reporting in these studies is guided by the 2015 Preferred Reporting Items for Systematic Review and Meta-Analysis of Individual Participant Data (PRISMA-IPD) guidelines. The growing number of IPD-MA published for stroke studies calls for an assessment of the compliance of these studies with the PRISMA-IPD statement. Methods: PubMed and EMBASE were searched for MA in stroke published between January 1, 2016, and March 30, 2020, in journals with impact factor >2. Literature reviews, scoping reviews, and aggregate MA were excluded. The final articles were scored using the 31-item PRISMA-IPD checklist. Results were depicted using descriptive statistics. Compliance with each item in PRISM-IPD guideline was recorded. The study was defined as compliant to IPD analyses if it satisfied all IPD specific items. Results: From an initial set of 321 articles, 31 met the final eligibility for data extraction. Only 4 (13%) described the use of PRISMA-IPD guidelines in their methodology, while 8/31 (26%) used the old PRISMA guidelines and 19/31 (61%) followed none. Regardless of mention of using IPD specific guidelines, 42% (n=13) of studies were compliant with all 4 IPD specific domains. The poorest areas of compliance were bias assessment within (32%) and across (39%) studies, reporting protocol and registration (42%), and reporting of IPD integrity (48%). The median journal impact factor was similar between the compliant (median, 8.1 [interquartile range, 5.4­39.9]) and noncompliant (median, 6 [interquartile range, 4.5­16.2]) groups (P=0.24). Similarly, the journal, country of correspondence, number of authors, number of studies included in MA, study sample size, and funding source were statistically similar between the groups. Conclusions: For the published IPD-MA stroke studies, the compliance with PRISMA-IPD statement and compliance with 4 IPD specific items was suboptimal. The journal, author, and study-related factors were not associated with compliance. Additional scrutiny measures to ensure adherence to mandated guidelines might increase the compliance. Several avenues to improve compliance and ensure optimal adherence are discussed.

Hepatocellular Carcinoma in Sub-Saharan Africa.

More than 80% of global hepatocellular carcinoma (HCC) patients are estimated to occur in sub-Saharan Africa (SSA) and Eastern Asia. The most common risk factor of HCC in SSA is chronic hepatitis B virus (HBV) infection, with the incidence highest in West Africa. HBV is highly endemic in SSA and is perpetuated by incomplete adherence to birth dose immunization, lack of longitudinal follow-up care, and impaired access to antiviral therapy. HBV may directly cause HCC through somatic genetic alterations or indirectly through altered liver function and liver cirrhosis. Other risk factors of HCC in SSA include aflatoxins and, to a lesser extent, African iron overload. HIV plus HBV co-infection increases the risk of developing HCC and is increasingly becoming more common because of improving the survival of patients with HIV infection. Compared with the rest of the world, patients with HCC in SSA have the lowest survival. This is partly due to the late presentation of HCC with advanced symptomatic disease as a result of underdeveloped surveillance practices. Moreover, access to care and resource limitations further limit outcomes for the patients who receive a diagnosis in SSA. There is a need for multipronged strategies to decrease the incidence of HCC and improve its outcomes in SSA.

Cranioplasty Using Customized 3-Dimensional-Printed Titanium Implants: An International Collaboration Effort to Improve Neurosurgical Care.

BACKGROUND: Evolutions in cranioplasty have allowed for the creation of customized implants via advances in 3-dimensional (3D) printing technology, although the high cost associated with this technique presents a barrier for low-income countries. Through an international collaboration, our team in Da Nang, Vietnam is able to create low-cost, customized titanium implants for patients with skull defects. We discuss the details of our collaboration and present our experience with this procedure. METHODS: We conducted a retrospective review of 35 patients who underwent cranioplasty using custom-made titanium implants. The molding and implant making processes were performed by our neurosurgeons using a 3D printer donated by the United Kingdom-based nongovernmental organization Facing the World. We obtained demographic and preoperative data (reason for skull defect, location, surface area measurement of defect) and postoperative data (complications, cosmetic outcome, and patient satisfaction). RESULTS: The median patient age was 27 years (range, 16-60 years). Primary indications for craniectomy included traumatic brain injury from motor vehicle accident (77.1%), cerebrovascular disease (11.4%), implant failure following previous cranioplasty (5.7%), and fall (5.7%). Postoperatively, all implants were found to have an excellent fit; at 6-month follow-up, none of the implants required removal. Complications included 4 postoperative hematomas and 1 surgical site infection. All the patients had improved aesthetic appearance and high satisfaction. CONCLUSIONS: Cranioplasty using customized titanium implants yields excellent results for patients with skull defects, demonstrating the practicality of this technique for cranioplasty in low-income countries. Our experience highlights the importance of ongoing international collaboration to improve neurosurgical care in these countries.

Jacques Forestier: Forgotten Contributions of a Rheumatologist to Spine Surgery.

Jacques Forestier (1890-1978) was a well-known rheumatologist and radiologist whose innovations have revolutionized spinal neurosurgery and rheumatology. He was well known as "Doctor Lipiodol" for his accidental discovery of spinal myelography, which he later extrapolated for use in many body cavities and their pathologies. He was the first to describe "senile ankylosing hyperostosis of the spine," which was later renamed "diffuse idiopathic skeletal hyperostosis." Furthermore, he is credited with the first use of gold salts as a disease-modifying therapy for rheumatoid arthritis. We have presented a historical vignette to chronicle the life of Jacques Forestier and his contributions to the field of spinal neurosurgery.

Suppression of phrenic nerve activity as a potential predictor of imminent sudden unexpected death in epilepsy (SUDEP).

Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death in patients with refractory epilepsy. Centrally-mediated respiratory dysfunction has been identified as one of the principal mechanisms responsible for SUDEP. Seizures generate a surge in adenosine release. Elevated adenosine levels suppress breathing. Insufficient metabolic clearance of a seizure-induced adenosine surge might be a precipitating factor in SUDEP. In order to deliver targeted therapies to prevent SUDEP, reliable biomarkers must be identified to enable prompt intervention. Because of the integral role of the phrenic nerve in breathing, we hypothesized that suppression of phrenic nerve activity could be utilized as predictive biomarker for imminent SUDEP. We used a rat model of kainic acid-induced seizures in combination with pharmacological suppression of metabolic adenosine clearance to trigger seizure-induced death in tracheostomized rats. Recordings of EEG, blood pressure, and phrenic nerve activity were made concomitant to the seizure. We found suppression of phrenic nerve burst frequency to 58.9% of baseline (p < 0.001, one-way ANOVA) which preceded seizure-induced death; importantly, irregularities of phrenic nerve activity were partly reversible by the adenosine receptor antagonist caffeine. Suppression of phrenic nerve activity may be a useful biomarker for imminent SUDEP. The ability to reliably detect the onset of SUDEP may be instrumental in the timely administration of potentially lifesaving interventions.

Big data, machine learning, and artificial intelligence: a field guide for neurosurgeons.

Big data has transformed into a trend phrase in healthcare and neurosurgery, becoming a pervasive and inescapable phrase in everyday life. The upsurge in big data applications is a direct consequence of the drastic boom in information technology as well as the growing number of internet-connected devices called the Internet of Things in healthcare. Compared with business, marketing, and other sectors, healthcare applications are lagging due to a lack of technical knowledge among healthcare workers, technological limitations in acquiring and analyzing the data, and improper governance of healthcare big data. Despite these limitations, the medical literature is flooded with big data-related articles, and most of these are filled with abstruse terminologies such as machine learning, artificial intelligence, artificial neural network, and algorithm. Many of the recent articles are restricted to neurosurgical registries, creating a false impression that big data is synonymous with registries. Others advocate that the utilization of big data will be the panacea to all healthcare problems and research in the future. Without a proper understanding of these principles, it becomes easy to get lost without the ability to differentiate hype from reality. To that end, the authors give a brief narrative of big data analysis in neurosurgery and review its applications, limitations, and the challenges it presents for neurosurgeons and healthcare professionals naive to this field. Awareness of these basic concepts will allow neurosurgeons to understand the literature regarding big data, enabling them to make better decisions and deliver personalized care.

Magnetic resonance-guided laser interstitial thermal therapy for posterior fossa neoplasms.

PURPOSE: Magnetic resonance-guided laser interstitial thermal therapy (LITT) has been increasingly used to treat a number of intracranial pathologies, though its use in the posterior fossa has been limited to a few small series. We performed a multi-institutional review of targets in the posterior fossa, reporting the efficacy and safety profile associated with laser ablation in this region of the brain. METHODS: A retrospective review of patients undergoing LITT in the posterior fossa was performed from August 2010 to March 2020. Patient demographic information was collected alongside the operative parameters and patient outcomes. Reported outcomes included local control of the lesion, postoperative complications, hospital length of stay, and steroid requirements. RESULTS: 58 patients across four institutions underwent LITT in the posterior fossa for 60 tumors. The median pre-ablation tumor volume was 2.24 cm3. 48 patients (50 tumors) were available for follow-up. An 84% (42/50) overall local control rate was achieved at 9.5 months median follow up. There were two procedural complications, including insertional hemorrhage and laser misplacement and 12/58 (21%) patients developed new neurological deficits. There was one procedure related death. The median length of hospital stay was 1 day, with 20.7% of patients requiring discharge to a rehabilitation facility. CONCLUSIONS: LITT is an effective approach for treating pathology in the posterior fossa. The average target size is smaller than what has been reported in the supratentorial space. Care must be taken to prevent injury to surrounding structures given the close proximity of critical structures in this region.

Nicolau Syndrome, Masquerader of Postinjection Sciatic Nerve Injury: Case Report and Review of Literature.

BACKGROUND: Sciatic nerve injury after inadvertent intramuscular gluteal injection is a well-described entity. We have presented a case of a rare and probably underdiagnosed pathological entity, Nicolau syndrome, which can be confused with injection palsy. CASE DESCRIPTION: We report the case of a 13-year-old boy who had presented with foot drop and urinary and fecal incontinence after an intramuscular injection of benzathine penicillin in the left gluteal region. On examination, the patient had multiple ecchymoses over the left gluteal region and back of the thigh, mild swelling of the left lower limb, and left foot drop. Meticulous examination also revealed a subtle weakness of the opposite limb. Nerve conduction studies revealed axonopathy involving multiple bilateral lower limb nerves. These unusual neurological-dermatological signs and electrophysiological findings raised the concern for an alternative pathology, which was later diagnosed as Nicolau syndrome. The patient experienced clinical and electrophysiological recovery after a course of oral steroids and physiotherapy during the next few months. CONCLUSIONS: Before diagnosing injection sciatic nerve injury, the possibility of medically treatable Nicolau syndrome should be considered. Neurosurgeons' familiarity with this pathology and a timely diagnosis is essential to plan appropriate treatment strategies.

Machine Learning Prediction Models for Diagnosing Hepatocellular Carcinoma with HCV-related Chronic Liver Disease.

BACKGROUND AND OBJECTIVE: Considered as one of the most recurrent types of liver malignancy, Hepatocellular Carcinoma (HCC) needs to be assessed in a non-invasive way. The objective of the current study is to develop prediction models for Chronic Hepatitis C (CHC)-related HCC using machine learning techniques. METHODS: A dataset, for 4423 CHC patients, was investigated to identify the significant parameters for predicting HCC presence. In this study, several machine learning techniques (Classification and regression tree, alternating decision tree, reduce pruning error tree and linear regression algorithm) were used to build HCC classification models for prediction of HCC presence. RESULTS: Age, alpha-fetoprotein (AFP), alkaline phosphate (ALP), albumin, and total bilirubin attributes were statistically found to be associated with HCC presence. Several HCC classification models were constructed using several machine learning algorithms. The proposed HCC classification models provide adequate area under the receiver operating characteristic curve (AUROC) and high accuracy of HCC diagnosis. AUROC ranges between 95.5% and 99%, plus overall accuracy between 93.2% and 95.6%. CONCLUSION: Models with simplistic factors have the power to predict the existence of HCC with outstanding performance.

Predictors of recurrence and survival of hepatocellular carcinoma: A prospective study including transient elastography and cancer stem cell markers.

BACKGROUND AND STUDY AIMS: To investigate whether the measurement of liver stiffness (LSM) using fibroscan and the serum Cancer Stem Cells (CSC): Ep-CAM and cytokeratin-19, could predict the recurrence of hepatocellular carcinoma (HCC) and their impact on clinical outcome and overall survival. PATIENTS AND METHODS: This is a prospective study, including 179 HCV-related HCC patients. All patients were treated following the BCLC guidelines. All HCC patients had transient elastography, measurements of Ep-CAM and cytokeratin-19 before and six months post-treatment. We looked for predictors of recurrence and performed a survival analysis using Kaplan-Meier estimates. RESULTS: TACE was the most common procedure (77.1%), followed by microwave ablation (15.6%). Complete ablation was achieved in 97 patients; 55 of them developed HCC recurrence. After treatment, LSM increased significantly with a significant reduction in CSCs levels in complete and partial response groups. The median time to observe any recurrence was 14 months. LSM increased significantly post-treatment in patients with recurrence versus no recurrence. Higher levels of CSCs were recorded at baseline and post-treatment in patients with recurrence but without statistical significance. We used univariate analysis to predict the time of recurrence by determining baseline CK-19 and platelet levels as the key factors, while the multivariate analysis determined platelet count as a single factor. The univariate analysis for prediction of overall survival included several factors, LSM and EpCAM (baseline and post-ablation) among them, while multivariate analysis included factors such as Child score B and incomplete ablation. CONCLUSION: Dynamic changes were observed in LSM and CSCs levels in response to HCC treatment and tumour recurrence. Child score and complete ablation are factors that significantly affect survival.

Hepatocellular Carcinoma Multidisciplinary Clinic-Cairo University (HMC-CU) score: A new simple score for diagnosis of HCC.

BACKGROUND AND STUDY AIMS: The risk of hepatocarcinogenesis depends on background liver factors, of which fibrosis is a major determinant. Serum markers and scores are of increasing importance in non-invasive diagnosis of hepatic fibrosis. Our aim was to predict the occurrence of hepatocellular carcinoma (HCC) using a non-invasive fibrosis score calculated using routine patient data. PATIENTS AND MTHODS: Our retrospective study included 1,291 hepatitis C related-HCC Egyptian patients (Group 1) recruited from the multidisciplinary HCC clinic, Faculty of Medicine, Cairo University in the period between February 2009 and June 2016 and 1072 chronic hepatitis C-naïve patients (Group 2) with advanced fibrosis (≥F3) and cirrhosis (F4). King score, Fibro Q score, Aspartate aminotransferase-to-platelet ratio index (APRI), AST to ALT ratio (AAR), LOK score, Göteborg University Cirrhosis Index (GUCI), Fibro-α and Biotechnology Research Center (BRC) scores were calculated for all patients. Regression analysis and receiver operating characteristics (ROC) were used to calculate the sensitivity, specificity and predictive values for significant scores with the best cut-off for predicting HCC. A regression equation was used to calculate predicted probabilities of HCC using the following variables; age, gender, haemoglobin, international normalised ratio (INR), albumin and alpha fetoprotein. The appropriate score cut-off points yielding optimal sensitivity and specificity were determined by ROC curve analysis. RESULTS: There was a highly significant difference between the two groups for all calculated scores (P = 0.0001). Our new score, the Hepatocellular Carcinoma Multidisciplinary Clinic-Cairo University (HMC-CU) score (Logit probability of HCC =  - 2.524 + 0.152*age - 0.121*Hb - 0.696*INR - 1.059*Alb + 0.022*AFP + 0.976*Sex. Male = 1, Female = 0), with a cut-off of 0.559 was superior to other scores for predicting HCC, having a sensitivity of 90% and specificity of 80.6%. CONCLUSION: The HMC-CU score is a promising, easily calculated, accurate, cost-effective score for HCC prediction in chronic HCV patients with advanced liver fibrosis.

Genetic variations in DNA-repair genes (XRCC1, 3, and 7) and the susceptibility to hepatocellular carcinoma in a cohort of Egyptians.

Chronic hepatitis C (CHC) is a worldwide etiology of chronic hepatic insult particularly in Egypt. DNA-repair systems are responsible for maintaining genomic integrity by countering threats posed by DNA lesions. Deficiency in the repair capacity due to genetic alterations in DNA-repair genes can lead to genomic instability and increased risk of cancer development. The present work aimed at studying the possible association between XRCC1-G28152A (rs25487), XRCC3-C18067T (rs861539), and XRCC7-G6721T (rs7003908) single nucleotide polymorphisms (SNPs) and the susceptibility to hepatocellular carcinoma (HCC) in Egyptian population. The study was conducted on 100 newly diagnosed HCC patients and 100 age- and sex-matched healthy controls. Laboratory workup revealed that all HCC patients have chronic hepatitis C viral infection. Genotyping of the studied SNPs was performed by real-time PCR. The heteromutant genotype of XRCC1 (GA) conferred an almost two-fold increased risk of HCC (OR , 2.35; 95% CI, 1.33-4.04). Regarding XRCC7, the heteromutant (TG) genotype conferred a two-fold increased risk of HCC (OR , 2.17; 95% CI, 1.23-3.82). Coinheritance of the polymorphic genotypes of XRCC1 and 7 was significantly higher in HCC cases than controls and was associated with an 11-fold increased risk of HCC (OR , 11.66; 95% CI, 2.77-49.13). The frequency of XRCC3 polymorphic genotypes in HCC patients was close to that of the controls.

An analysis of cross-continental scholarship requirements during neurosurgical training and national research productivity.

OBJECTIVE: Engagement in research and scholarship is considered a hallmark of neurosurgical training. However, the participation of neurosurgical trainees in this experience has only recently been analyzed and described in the United States, with little, if any, data available regarding the research environment in neurosurgical training programs across the globe. Here, the authors set out to identify requirements for research involvement and to quantify publication rates in leading neurosurgical journals throughout various nations across the globe. METHODS: The first aim was to identify the research requirements set by relevant program-accrediting and/or board-certifying agencies via query of the literature and published guidelines. For the second part of the study, the authors attempted to determine each country's neurosurgical research productivity by quantifying publications in the various large international neurosurgical journals-World Neurosurgery, Journal of Neurosurgery, and Neurosurgery-via a structured search of PubMed. RESULTS: Data on neurosurgical training requirements addressing research were available for 54 (28.1%) of 192 countries. Specific research requirements were identified for 39 countries, partial requirements for 8, and no requirements for 7. Surprisingly, the authors observed a trend of increased average research productivity with the absence of designated research requirements, although this finding is not unprecedented in the literature. CONCLUSIONS: A variety of countries of various sizes and neurosurgical workforce densities across the globe have instituted research requirements during training and/or prior to board certification in neurosurgery. These requirements range in intensity from 1 publication or presentation to the completion of a thesis or dissertation and occur at various time points throughout training. While these requirements do not correlate directly to national research productivity, they may provide a foundation for developing countries to establish a culture of excellence in research.