Real-world challenges for hepatitis C virus medications: a critical overview.

From 2010, the landscape of hepatitis C therapeutics has been changed rapidly, and today we are standing at a cusp of a pharmacological revolution where highly effective and interferon (IFN)-free direct acting antivirals (DAAs) are already on the market. Such treatment paradigms attain 90-95% sustained virologic response (SVR; undetectable viral load at week 12 or 24 at the end of therapy) rates in treated individuals compared to 50-70% with treatment completion of dual-therapy-pegylated interferon (PEG-IFN) and ribavirin (RBV). As the major goal now for the hepatologists, clinicians, physicians, and health care workers is likely to eradicate hepatitis C infection in parallel to treatment, the demand is for a one-size-fits-all pill that could be prescribed beyond the limitations of hepatitis C genotype, viral load, previous treatment history, advanced hepatic manifestations (fibrosis, cirrhosis) and antiviral drug resistance. Although the new treatment strategies have shown high cure rates in clinical trials, such treatment paradigms are posing dilemmas too in real-world clinical practice. Therapy cost, treatment access to low and middle-income countries, treatment-emergent adverse events, lack of effective viral screening and disease progression simulation models are potential challenges in this prospect. This review article deeply overviews the challenges encountered while surmounting the burden of hepatitis C around the world.

Hepatitis C virus infection treatment: An era of game changer direct acting antivirals and novel treatment strategies.

Chronic hepatitis C virus infection and associated liver diseases represent a major health care burden all over the world. The current standard of care, i.e. peginterferon-alfa (PEG-IFNα) plus ribavirin (RBV) are associated with frequent and sometimes serious adverse effects and contraindications, which further limit their therapeutic efficacy. The approval of first and second generation HCV protease inhibitors represents a major breakthrough in the development of novel direct acting antivirals (DAAs) against different HCV genotypes and establishes a new standard of care for chronically infected HCV genotypes 1 patients. Similarly, next generation protease inhibitors and HCV RNA polymerase inhibitors have shown better pharmacokinetics and pharmacodynamics in terms of broader HCV genotypes coverage, better safety profile, fewer drug interactions and possible once daily administration than first generation direct acting antivirals. The testing of adenovirus-based vector vaccines, which escalates the innate and acquired immune responses against the most conserved regions of the HCV genome in chimpanzees and humans, may be a promising therapeutic approach against HCV infection in coming future. This review article presents up-to-date knowledge and recent developments in HCV therapeutics, insights the shortcomings of current HCV therapies and key lessons from the therapeutic potential of improved anti-HCV treatment strategies.

Synergistic effects of herpes oncolytic virus and cyclophosphamide for recurrent malignant glioma: a narrative review.

Gliomas, comprising nearly 80% of brain malignancies, present a formidable challenge with glioblastomas being the most aggressive subtype. Despite multidisciplinary care, including surgery and chemoradiotherapy, the prognosis remains grim, emphasizing the need for innovative treatment strategies. The blood-brain barrier complicates drug access, and the diverse histopathology hinders targeted therapies. Oncolytic herpes viruses (oHSVs), particularly HSV1716, G207, and rQNestin34.5v, show promise in glioma treatment by selectively replicating in tumor cells. Preclinical and clinical studies demonstrate the safety and efficacy of oHSVs, with T-Vec being FDA-approved. However, challenges like viral delivery limitations and antiviral responses persist. The combination of oHSVs and combining cyclophosphamide (CPA) addresses these challenges, demonstrating increased transgene expression and viral activity. The immunosuppressive properties of CPA, particularly in metronomic schedules, enhance oHSV efficacy, supporting the development of this combination for recurrent malignant gliomas. CPA with oHSVs enhances viral oncolysis and extends survival. CPA's immunomodulatory effects, suppressing regulatory T cells, improve oHSV efficiency. While obstacles remain, this synergistic approach offers hope for improved outcomes, necessitating further research and clinical validation.

Comparative analysis of exoscope-assisted spine surgery versus operating microscope: A systematic review.

Background: Limitations in the operative microscope (OM)'s mobility and suboptimal ergonomics created the opportunity for the development of the exoscope. This systematic review aims to evaluate the advantages and disadvantages of exoscopes and OMs in spine surgery. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a systematic search was conducted in the major research databases. All studies evaluating the exoscopes and/or OMs in spinal procedures were included. Results: There were 602 patients included in the 16 studies, with 539 spine surgery patients, 19 vascular cases, 1 neural pathology case, 19 cranial cases, and 24 tumor pathologies. When examining surgical outcomes with the exoscope, results were mixed. Compared to the OM, exoscope usage resulted in longer operative times in 7 studies, comparable times in 3 studies, and shorter operative times in 3 studies. Two studies found similar lengths of stay (LOS) for both tools, two reported longer LOS with exoscopes, and one indicated shorter hospital LOS with exoscopes. One study reported higher exoscope-related blood loss (EBL), but four other studies consistently showed reduced EBL. In terms of image quality, illumination, dynamic range, depth perception, ergonomics and cost-effectiveness, the exoscope was consistently rated superior, while findings across studies were mixed regarding the optical zoom ratio and mean scope adjustment (MSA). The learning curve for exoscope use was consistently reported as shorter in all studies. Conclusion: Exoscopes present a viable alternative to OMs in spine surgery, offering multiple advantages, which supports their promising role in modern neurosurgical practice.

Neurosurgical Malpractice Litigation: A Systematic Review and Meta-Analysis.

BACKGROUND: Neurosurgery has 1 of the highest risks for medical malpractice claims. We reviewed the factors associated with neurosurgical malpractice claims and litigation in the United States and reported the outcomes through a systematic review of the literature. METHODS: We conducted a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines using the Medline, Embase, Cochrane, PubMed, and Google Scholar databases. We sought to identify pertinent studies containing information about medical malpractice claims and outcomes involving neurosurgeons in the United States. RESULTS: We identified 15 retrospective studies spanning from 2002 to 2023 that reviewed over 7890 malpractice claims involving practicing neurosurgeons in the United States. Disparities were evident in neurosurgical litigation, with 474 cases linked to brain-related surgeries and a larger proportion, 1926 cases, tied to spine surgeries. The most commonly filed claims were intraprocedural errors (37.4%), delayed diagnoses (32.1%), and failure to treat (28.8%). Less frequently filed claims included misdiagnosis or choice of incorrect procedure (18.4%), occurrence of death (17.3%), test misinterpretation (14.4%), failure to appropriately refer patients for evaluation/treatment (14.3%), unnecessary surgical procedures (13.3%), and lack of informed consent (8.3%). The defendant was favored in 44.3% of claims, while in 31.3% of lawsuits were dropped, 17.7% of verdicts favored the plaintiff, and 16.6% reached an out of court settlement. Only 3.5% of lawsuits found both parties liable. CONCLUSION: Neurosurgery is a high-risk specialty with 1 of the highest rates of malpractice claims. Spine claims had a significantly higher rate of filed malpractice claims, while cranial malpractice claims were associated with higher litigation compensation. Predictably, spinal cord injuries play a crucial role in predicting litigation. Importantly, nonsurgical treatments are also a common source of liability in neurosurgical practice.

Re-emergence of Lassa fever in Nigeria: A new challenge for public health authorities.

The Lassa virus is an RNA virus belonging to the Arenaviridae family. It is responsible for Lassa fever, an acute viral zoonosis of the severe hemorrhagic fever type with manifestations of fever, muscle pain, sore throat, nausea, vomiting, and chest and abdominal pain. Lassa fever is endemic in West Africa, where the first case was reported in 1969 in Lassa, a town in Nigeria, more than 50 years ago, and it is estimated that nearly 5000 deaths occur in West Africa each year. Nigeria is one of the endemic hotspots and has experienced numerous recurrent outbreaks of Lassa fever due to the increased multiplication of the host reservoir, Mastomys natalensis. For the Lassa epidemics in 2022 and January 2023 alone, Nigeria accounts for a quarter of the annual deaths from this disease. Poor lifestyle and hygiene, difficulty in diagnosis due to nonspecific symptomatology, lack of effective treatment based on clinical evidence, an ineffective human immunization program combined with a health system that is not adapted or equipped to control and prevent recurrent deadly epidemics, and an outdated regional disease surveillance system in West Africa are some of the challenges that must be overcome to rapidly and effectively eradicate this disease, whose area of spread is constantly expanding as a result of the movement of populations in the context of economic and socio-cultural activities.

Role of deep brain stimulation (DBS) in addiction disorders.

Background: Addiction disorders pose significant challenges to public health, necessitating innovative treatments. This assesses deep brain stimulation (DBS) as a potential intervention for addiction disorders. Methods: A literature review was carried out with a focus on the role of DBS in addiction disorders and its future implications in neurosurgical research. Results: The online literature shows that DBS precisely modulates certain brain regions to restore addiction-related neural circuits and promote behavioral control. Conclusion: Preclinical evidence demonstrates DBS's potential to rebalance neural circuits associated with addiction, and early clinical trials provide encouraging outcomes in enhancing addiction-related outcomes. Ethical considerations, long-term safety, and personalized patient selection require further investigation.

Role of preoperative erythropoietin in the optimization of preoperative anemia among surgical patients - A systematic review and meta-analysis.

Preoperative anemia is a common finding. Preoperative allogeneic transfusion, iron therapy, vitamin supplementation and erythropoietin therapy are the current management strategies for preoperative anemia. Previous reviews regarding erythropoietin were limited to specialties, provided little evidence regarding the benefits and risks of erythropoietin in managing preoperative anemia and included non-anemic patients. The purpose of our systematic review was to determine the role of erythropoietin solely in preoperatively anemic patients and to investigate the complications of this treatment modality to produce a guideline for preoperative management of anemic patients for all surgical specialties. The PubMed/Medline, Google Scholar, and Cochrane Library were searched for randomized trials evaluating the efficacy of erythropoietin in preoperative anemia. The risk ratio (RR) and standardized mean difference (SMD) was used to pool the estimates of categorical and continuous outcomes, respectively. Allogeneic transfusion and complications and the 90-day mortality were the primary outcomes, while the postoperative change in hemoglobin, bleeding in milliliters and the number of red blood cell (RBC) packs transfused were the secondary outcomes. Results: Eight studies were included, comprising 734 and 716 patients in the erythropoietin group and non-erythropoietin group, respectively. The pooled estimate by RR for allogeneic transfusion was 0.829 (p = 0.049), while complications and the 90-day mortality were among the 1,318 (p = 0.18) patients. Conclusion: Preoperative erythropoietin provides better outcomes, considering the optimization of preoperative anemia for elective surgical procedures. The benefits of erythropoietin are significantly higher, compared to the control group, while the risks remain equivocal in both groups. We recommend preoperative erythropoietin in anemic patients.

The future of artificial intelligence in neurosurgery: A narrative review.

Background: Artificial intelligence (AI) and machine learning (ML) algorithms are on the tremendous rise for being incorporated into the field of neurosurgery. AI and ML algorithms are different from other technological advances as giving the capability for the computer to learn, reason, and problem-solving skills that a human inherits. This review summarizes the current use of AI in neurosurgery, the challenges that need to be addressed, and what the future holds. Methods: A literature review was carried out with a focus on the use of AI in the field of neurosurgery and its future implication in neurosurgical research. Results: The online literature on the use of AI in the field of neurosurgery shows the diversity of topics in terms of its current and future implications. The main areas that are being studied are diagnostic, outcomes, and treatment models. Conclusion: Wonders of AI in the field of medicine and neurosurgery hold true, yet there are a lot of challenges that need to be addressed before its implications can be seen in the field of neurosurgery from patient privacy, to access to high-quality data and overreliance on surgeons on AI. The future of AI in neurosurgery is pointed toward a patient-centric approach, managing clinical tasks, and helping in diagnosing and preoperative assessment of the patients.

Elusive tuberculous meningitis with rare neurological complication of longitudinally extensive transverse myelitis: a case report.

INTRODUCTION: Longitudinally extensive transverse myelitis (LETM) is inflammation of the spinal cord that spans three or more spinal segments. LETM is a rare occurrence on its own and has seldom been reported with tuberculous meningitis (TBM), the rarest and deadliest of tuberculous manifestations. TBM is usually seen in children, the immunocompromised, or those with a previous history of tuberculosis infection. CASE PRESENTATION: A 24-year-old healthy male with no co-morbidities or history of tuberculosis presented with fever and headache for the past 3 months. The patient's Kernig's and Brudzinski's signs were both negative, with bilateral abnormal plantar reflexes. The neurological level of injury was T8 and the patient was classified as AIS grade A. His CSF analysis showed a lymphocytic picture. However, both GeneXpert and Ziehl-Neelsen staining came back negative for Mycobacterium tuberculosis. MRI scans of the brain and thoracic spine revealed enhancing nodules and ring lesions in the brain and spinal cord, along with the rare complication of LETM, extending from T2 to T9. DISCUSSION: Although Mycobacterium tuberculosis was never isolated, the patient started recovering as soon as antituberculous therapy was initiated. Hence, more emphasis needs to be placed on radiological imaging in the management of rare medical emergencies like tuberculous meningitis, especially in areas where tuberculosis is rampant and endemic, rather than waiting for a positive culture. This case report also demonstrates the growing evidence that transverse myelitis and/or LETM is associated with TBM.

Role of preoperative erythropoietin in the optimization of preoperative anemia among surgical patients — A systematic review and meta-analysis

Abstract Preoperative anemia is a common finding. Preoperative allogeneic transfusion, iron therapy, vitamin supplementation and erythropoietin therapy are the current management strategies for preoperative anemia. Previous reviews regarding erythropoietin were limited to specialties, provided little evidence regarding the benefits and risks of erythropoietin in managing preoperative anemia and included non-anemic patients. The purpose of our systematic review was to determine the role of erythropoietin solely in preoperatively anemic patients and to investigate the complications of this treatment modality to produce a guideline for preoperative management of anemic patients for all surgical specialties. The PubMed/Medline, Google Scholar, and Cochrane Library were searched for randomized trials evaluating the efficacy of erythropoietin in preoperative anemia. The risk ratio (RR) and standardized mean difference (SMD) was used to pool the estimates of categorical and continuous outcomes, respectively. Allogeneic transfusion and complications and the 90-day mortality were the primary outcomes, while the postoperative change in hemoglobin, bleeding in milliliters and the number of red blood cell (RBC) packs transfused were the secondary outcomes. Results: Eight studies were included, comprising 734 and 716 patients in the erythropoietin group and non-erythropoietin group, respectively. The pooled estimate by RR for allogeneic transfusion was 0.829 (p = 0.049), while complications and the 90-day mortality were among the 1,318 (p = 0.18) patients. Conclusion: Preoperative erythropoietin provides better outcomes, considering the optimization of preoperative anemia for elective surgical procedures. The benefits of erythropoietin are significantly higher, compared to the control group, while the risks remain equivocal in both groups. We recommend preoperative erythropoietin in anemic patients.

In vitro inhibitory analysis of consensus siRNAs against NS3 gene of hepatitis C virus 1a genotype.

OBJECTIVE: To explore inhibitory effects of genome-specific, chemically synthesized siRNAs (small interference RNA) against NS3 gene of hepatitis C virus (HCV) 1a genotype in stable Huh-7 (human hepatoma) cells as well as against viral replication in serum-inoculated Huh-7 cells. METHODS: Stable Huh-7 cells persistently expressing NS3 gene were produced under antibiotic gentamycin (G418) selection. The cell clones resistant to 1000 µg antibiotic concentration (G418) were picked as stable cell clones. The NS3 gene expression in stable cell clone was confirmed by RT-PCR and Western blotting. siRNA cell cytotoxicity was determined by MTT cell proliferation assay. Stable cell lines were transfected with sequence specific siRNAs and their inhibitory effects were determined by RT-PCR, real-time PCR and Western blotting. The viral replication inhibition by siRNAs in serum inoculated Huh-7 cells was determined by real-time PCR. RESULTS: RT-PCR and Western blot analysis confirmed NS3 gene and protein expression in stable cell lines on day 10, 20 and 30 post transfection. MTT cell proliferation assay revealed that at most concentrated dose tested (50 nmol/L), siRNA had no cytotoxic effects on Huh-7 cells and cell proliferation remained unaffected. As demonstrated by the siRNA time-dependent inhibitory analysis, siRNA NS3-is44 showed maximum inhibition of NS3 gene in stable Huh-7 cell clones at 24 (80%, P = 0.013) and 48 h (75%, P = 0.002) post transfection. The impact of siRNAs on virus replication in serum inoculated Huh-7 cells also demonstrated significant decrease in viral copy number, where siRNA NS3-is44 exhibited 70% (P < 0.05) viral RNA reduction as compared to NS3-is33, which showed a 64% (P < 0.05) decrease in viral copy number. siRNA synergism (NS3-is33 + NS3-is44) decreased viral load by 84% (P < 0.05) as compared to individual inhibition by each siRNA (i.e., 64%-70% (P < 0.05)) in serum-inoculated cells. Synthetic siRNAs mixture (NS5B-is88 + NS3-is33) targeting different region of HCV genome (NS5B and NS3) also decreased HCV viral load by 85% (P < 0.05) as compared to siRNA inhibitory effects alone (70% and 64% respectively, P < 0.05). CONCLUSIONS: siRNAs directed against NS3 gene significantly decreased mRNA and protein expression in stable cell clones. Viral replication was also vividly decreased in serum infected Huh-7 cells. Stable Huh-7 cells expressing NS3 gene is helpful to develop anti-hepatitis C drug screening assays. siRNA therapeutic potential along with other anti-HCV agents can be considered against hepatitis C.

Assessment methods for angiogenesis and current approaches for its quantification.

Angiogenesis is a physiological process which describes the development of new blood vessels from the existing vessels. It is a common and the most important process in the formation and development of blood vessels, so it is supportive in the healing of wounds and granulation of tissues. The different assays for the evaluation of angiogenesis have been described with distinct advantages and some limitations. In order to develop angiogenic and antiangiogenic techniques, continuous efforts have been resulted to give animal models for more quantitative analysis of angiogenesis. Most of the studies on angiogenic inducers and inhibitors rely on various models, both in vitro, in vivo and in ova, as indicators of efficacy. The angiogenesis assays are very much helpful to test efficacy of both pro- and anti- angiogenic agents. The development of non-invasive procedures for quantification of angiogenesis will facilitate this process significantly. The main objective of this review article is to focus on the novel and existing methods of angiogenesis and their quantification techniques. These findings will be helpful to establish the most convenient methods for the detection, quantification of angiogenesis and to develop a novel, well tolerated and cost effective anti-angiogenic treatment in the near future.