Evaluation of the expression of fibrosis-related genes as non-invasive diagnostic biomarkers for cirrhotic HCV-infected patients.

Liver cirrhosis is a condition with high mortality that poses a significant health and economic burden worldwide. The clinical characteristics of liver cirrhosis are complex and varied. Therefore, the evaluation of immune infiltration-involved genes incirrhosis has become mandatory in liver disease research, not only to identify the potential biomarkers but also to provide important insights into the underlying mechanisms of the disease. In this study, we aimed to investigate the expression profile of cytokine genes in peripheral blood mononuclear cells (PBMCs) of HCV patients and identify the gene expression signature associated with advanced cirrhosis. A cross-sectional study of 90 HCV genotype 4 patients, including no fibrosis patients (F0, n = 24), fibrotic patients (F1-F3, n = 36), and cirrhotic patients (F4, n = 30) has been conducted. The expression of cytokine genes was analyzed by quantitative real-time PCR in the subjects' PBMCs, and the serum level of TGFß2 was measured by ELISA. Our findings showed that the expression level of the TGIF1 transcript was lower in cirrhotic and fibrotic patients compared to no fibrosis patients (p = 0.046 and 0.022, respectively). Also, there was an upregulation of the TGFß1 gene in cirrhotic patients relative to fibrotic patients (p = 0.015). Additionally, the cirrhotic patients had higher expression levels of the TGF-ß2 transcript and elevated levels of the TGF-ß2 protein than patients with no cirrhosis or fibrosis. According to the ROC analysis, TGFß1, TGIF1 transcripts, and TGFß2 protein have a good discriminatory performance in distinguishing between cirrhotic, fibrotic, and non-fibrotic patients. Our results suggested that the expression of TGIF1, TGF-ß1, and TGF-ß2 genes in PBMCs may provide a valuable tool for identifying patients with advanced cirrhosis and that TGF-ß and TGIF1 may be potential biomarkers for cirrhosis. These findings may have implications for the diagnosis and treatment of cirrhosis in HCV patients.

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.

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.

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.

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.

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.

Genetic variations in death receptor domain 4 gene and the susceptibility to hepatitis C related hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide, particularly in Egypt. The role of apoptosis in tumorigenesis has been well-documented and resistance to apoptosis is a hallmark of cancer. Several studies discussed the association between death receptor 4 (DR4) genetic variants and HCC risk. AIM: To study the possible link between DR4 gene polymorphisms and the susceptibility to HCC. METHODS: Genotyping of DR4-C626G, -A683C, and DR4-A1322G single nucleotide polymorphisms (SNP) was determined by polymerase chain reaction assay for 100 de novo HCV-related HCC patients, 100 chronic hepatitis C-related liver cirrhosis patients, and 150 healthy controls. RESULTS: DR4-A1322G polymorphic genotypes (AG and GG) were significantly higher in HCC and cirrhotic patients than controls. The AG genotype conferred two-fold increased risk of HCC (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.56-3.51) and the risk increased to three-fold for the GG genotype (OR, 3.51; 95%CI, 2.33-5.28). The frequency of DR4-C626G and -A683C SNPs in HCC and cirrhotic patients were not significantly different from the controls. Combined genotype analysis showed that coinheritance of the polymorphic genotypes of DR4-C626G and -A1322G conferred nine-fold increased risk of HCC (OR, 9.34; 95%CI, 3.76-23.12). The risk increased to be 12-fold when DR4-A683C and -A1322G variants were coinherited (OR, 11.9; 95%CI, 4.82-29.39). Coexistence of the variant genotypes of the three SNPs conferred almost 10-fold increased risk of HCC (OR, 9.75; 95%CI, 1.86-51.19). CONCLUSIONS: The G allele of DR4 -A1322G could be considered as a novel independent molecular predictor for HCV-related HCC in the Egyptian population.

Planning and prioritizing direct-acting antivirals treatment for HCV patients in countries with limited resources: Lessons from the Egyptian experience.

BACKGROUND AND AIMS: The introduction of direct-acting antivirals for hepatitis C virus (HCV) in Egypt led to massive treatment uptake, with Egypt's national HCV treatment program becoming the largest in the world. The aim of this paper is to present the Egyptian experience in planning and prioritizing mass treatment for patients with HCV, highlighting the difficulties and limitations of the program, as a guide for other countries of similarly limited resources. METHODS: Baseline data of 337,042 patients, treated between October 2014 to March 2016 in specialized viral hepatitis treatment centers, were grouped into three equal time intervals of six months each. Patients were treated with different combinations of direct-acting antivirals, with or without ribavirin and pegylated interferon. Baseline data, percentage of patients with known outcome, and sustained virological response at week 12 (SVR12) were analyzed for the three cohorts. The outcomes of 94,258 patients treated in the subsequent two months are also included. RESULTS: For cohort-1, treatment was prioritized for patients with advanced fibrosis (F3-F4 fibrosis, liver stiffness ≥9.5 kPa, or Fibrosis-4 ≥3.25). Starting cohort-2, all stages of fibrosis were included (F0-F4). The prioritization strategy in the initial phase caused delays in enrollment and massive backlogs. Cohort-1 patients were significantly older, and more had advanced fibrosis compared to subsequent cohorts. The percentage of patients with known SVR12 results were low initially, and increased with each cohort, as several methods to capture patient results were adopted. Sofosbuvir-ribavirin therapy for 24 weeks had the lowest SVR12 rate (82.7%); while other therapies were associated with SVR12 rates between 94% and 98%. CONCLUSION: Prioritization based on fibrosis stage was not effective and enrollment increased greatly only after including all stages of fibrosis. The availability of generic drugs reduced costs, and helped massively increase uptake of the program. Post-treatment follow-up was initially very low, and although this has increased, further improvement is still needed. LAY SUMMARY: We are presenting the largest national program for HCV treatment in the world. We clearly demonstrate that hepatitis C can be cured efficiently in large scale real-life programs. This is a clear statement that global HCV eradication is foreseeable, providing a model for other countries with limited resources and prevalent HCV. Moreover, the availability of generic products has influenced the success of this program.

Reversion-Inducing-Cysteine-Rich Protein With Kazal Motifs (RECK) Gene Single Nucleotide Polymorphism With Hepatocellular Carcinoma: A Case-Control Study.

BACKGROUND: The reversion-inducing-cysteine-rich protein with kazal motifs (RECK) gene is a transformation suppressor gene that can negatively regulate matrix metalloproteinases (MMPs) and inhibit tumor invasion, angiogenesis, and metastasis. So, the aim of this study was to analyze the effect of RECK gene rs 11788747 single nucleotide polymorphism (SNP) on hepatocellular carcinoma (HCC) susceptibility and its relation to various clinical and laboratory data of the patients. METHODS: This is a case-control study including 200 HCC patients and 200 healthy controls. RECK rs 11788747 genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: RECK rs 11788747 A/G and G/G genotypes frequencies were significantly higher in HCC patients compared to the healthy controls. The HCC patients possessing at least one polymorphic G allele were significantly at a higher risk of developing lymph nodes involvement and distant metastasis. CONCLUSION: This study revealed the role of RECK rs 11788747 SNP in HCC in Egyptian patients, which consequently might be used as a prognostic tool and could be added to its therapeutic strategies.

Microwave ablation versus transarterial chemoembolization in large hepatocellular carcinoma: prospective analysis.

OBJECTIVE: Limited therapies are offered for large hepatocellular carcinoma (HCC). It carries dismal prognosis and efforts tried changing its management from a palliative to a curative mode. Transarterial chemoembolization (TACE) is a palliative procedure that may have survival benefit if compared to non-management of large lesions. Microwave ablation (MWA) has emerged as a relatively new technique with promise of larger and faster ablation. We aim to evaluate the efficacy and safety of percutaneous MWA versus TACE for large tumors (5-7 cm) and to assess their effects on local tumor progression and survival. PATIENTS AND METHODS: Sixty-four patients with large lesions are managed in our multidisciplinary HCC clinic and were divided into two groups treated either by MWA or TACE. Complete response rate, local recurrence, de novo lesions, and overall survival analysis are compared between both procedures. RESULTS: Both groups were comparable as regards the demographic and ultrasonographic features. MWA showed higher rates of complete ablation (75%) with fewer sessions, lower incidence of tumor recurrence (p = 0.02), development of de novo lesions (p = 0.03), occurrence of post-treatment ascites (p = 0.003), and higher survival rates (p = 0.04). The mean survival of the microwave group was 21.7 months with actuarial probability of survival at 12 and 18 months 78.2% and 68.4%, respectively. The mean survival of the TACE group was 13.7 months with actuarial probability of survival at 12 and 18 months being 52.4% and 28.6%, respectively. CONCLUSION: MWA showed better results than TACE in the management of large HCC lesions.

Dynamic interplay between CXCL levels in chronic hepatitis C patients treated by interferon.

BACKGROUND: Combined pegylated interferon-α and ribavirin therapy has sustained virological response (SVR) rates of 54% to 61%. Pretreatment predictors of SVR to interferon therapy have not been fully investigated yet. The current study assesses a group of chemokines that may predict treatment response in Egyptian patients with chronic HCV infection. PATIENTS AND METHODS: CXCL5, CXCL9, CXCL11, CXCL12, CXCL 13, CXCL 16 chemokines and E-Cadherin were assayed in 57 chronic HCV patients' sera using quantitative ELISA plate method. All studied patients were scheduled for combined pegylated interferon alpha and ribavirin therapy (32 patients received pegylated interferon α 2b, and 25 patients received pegylated interferon α 2a). Quantitative hepatitis C virus RNA was done by real time RT-PCR and HCV genotyping by INNOLIPAII. RESULTS: There was no significant difference (p > 0.05) in baseline HCV RNA levels between responders and non-responders to interferon. A statistically significant difference in CXCL13 (p = 0.017) and E-Cadherin levels (P = 0.041) was reported between responders and nonresponders at week 12. Significant correlations were found between changes in the CXCL13 levels and CXCL9, CXCL16, E-cadherin levels as well as between changes in E-cadherin levels and both CXCL16 and ALT levels that were maintained during follow up. Also, significant changes have been found in the serum levels of CXCL5, CXCL13, and CXCL16 with time (before pegylated interferon α 2 a and α 2 b therapy, and at weeks 12 and 24) with no significant difference in relation to interferon type and response to treatment. CONCLUSION: Serum levels of CXCL13 and E-Cadherin could be used as surrogate markers to predict response of combined PEG IFN-α/RBV therapy, especially at week 12. However, an extended study including larger number of patients is needed for validation of these findings. CLINICAL TRIAL NO: NCT01758939.

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.

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.

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.

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.

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.

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.