The effectiveness of hematopoietic stem cell transplantation in treating pediatric sickle cell disease: Systematic review and meta-analysis.

Background: Patients with sickle cell disease (SCD) have just one recognized curative therapy option: hematopoietic stem cell transplantation (HSCT), which results in a long-lasting improvement in the clinical phenotype. Here, we assessed the effectiveness of HSCT in treating children with SCD by a systematic review and meta-analysis. Methods: Up until January 2024, a comprehensive search was done using Web of Science, CINAHL, Embase, Google Scholar, Cochrane Library, PubMed/Medline, and Embase. Two reviewers worked separately to extract the data, and Newcastle-Ottawa Quality Assessment tool was used to assess the research's quality. The outcomes analyzed were Overall survival (OS), event-free survival (EFS), graft failure (GF) and mortality. Results: Nineteen papers satisfied our inclusion requirements and were assessed to be of fair quality. The pooled rate of OS was high (92%; 95% CI: 90.3%-93.5%). Similar finding was detected for EFS (85.8%; 95% CI: 83.7%-87.7%). In the other hand, pooled rates of GF and mortality were 6.9% (95% CI: 5.3%-8.9%) and 7.4% (95% CI: 5%-10.7%), respectively. A significant publication bias was detected for OS, EFS and GF outcomes. Subgroups analysis showed that study design was the major source of heterogeneity. Conclusion: Our results show that HSCT is effective and safe, with pooled survival rates above 90%. It is important to assess innovative tactics in light of the alarming GF and mortality rates.

Novel Piperazine Derivatives as Potent Antihistamine, Anti-Inflammatory, and Anticancer Agents, their Synthesis and Characterization.

INTRODUCTION: In this study, a series of novel piperazine derivatives were synthesised with high-to-good yields, and their structural analogies were confirmed using FTIR, 1H-NMR, and LC-MS techniques. METHOD: The synthesised compounds were evaluated for antioxidant and antimicrobial activities. Among the four synthesised piperazine derivatives, compound PD-2 exhibited relatively good antioxidant activity, with an IC50 value of 2.396 µg/mL, while the other three derivatives showed moderate to low antioxidant activity. Furthermore, compound PD-2 displayed antimicrobial activity against Pseudomonas aeruginosa, a gram-negative bacterium, and Candida albicans, a fungus. However, all four compounds showed strong resistance against grampositive bacteria, Staphylococcus aureus. RESULT: Additionally, compound PD-1 exhibited significant antihistamine activity, eliciting an 18.22% reduction in histamine levels. Both PD-1 and PD-2 demonstrated noteworthy anti-inflammatory activity in a dosedependent manner (5-10µM), leading to the inhibition of nitrite production up to 39.42% and 33.7% at higher concentrations (10 µM) and inhibition of tumour necrosis factor-alpha (TNF-α) generation up to 56.97% and 44.73% at 10 µM, respectively. Additionally, both novel molecules PD-1 and PD-2 effectively restrained the growth of HepG2 cells in a manner that is dependent on the dosage up to 55.44% and 90.45% at the highest concentrations (100 µg/mL), respectively. CONCLUSION: These findings substantiate the rationale for further investigation into the novel series of persuasive piperazine analogues as potential agents with anti-inflammatory, antihistamine and anticancer properties.

A Roadmap for Selecting and Utilizing Optimal Features in scRNA Sequencing Data Analysis for Stem Cell Research: A Comprehensive Review.

Stem cells and the cells they produce are unique because they vary from one cell to another. Traditional methods of studying cells often overlook these differences. However, the development of new technologies for studying individual cells has greatly changed biological research in recent years. Among these innovations, single-cell RNA sequencing (scRNA-seq) stands out. This technique allows scientists to examine the activity of genes in each cell, across thousands or even millions of cells. This makes it possible to understand the diversity of cells, identify new types of cells, and see how cells differ across different tissues, individuals, species, times, and conditions. This paper discusses the importance of scRNA-seq and the computational tools and software that are essential for analyzing the vast amounts of data generated by scRNA-seq studies. Our goal is to provide practical advice for bioinformaticians and biologists who are using scRNA-seq to study stem cells. We offer an overview of the scRNA-seq field, including the tools available, how they can be used, and how to present the results of these studies effectively. Our findings include a detailed overview and classification of tools used in scRNA-seq analysis, based on a review of 2,733 scientific publications. This review is complemented by information from the scRNA-tools database, which lists over 1,400 tools for analyzing scRNA-seq data. This database is an invaluable resource for researchers, offering a wide range of options for analyzing their scRNA-seq data.

Distributed neural representations of conditioned threat in the human brain.

Detecting and responding to threat engages several neural nodes including the amygdala, hippocampus, insular cortex, and medial prefrontal cortices. Recent propositions call for the integration of more distributed neural nodes that process sensory and cognitive facets related to threat. Integrative, sensitive, and reproducible distributed neural decoders for the detection and response to threat and safety have yet to be established. We combine functional MRI data across varying threat conditioning and negative affect paradigms from 1465 participants with multivariate pattern analysis to investigate distributed neural representations of threat and safety. The trained decoders sensitively and specifically distinguish between threat and safety cues across multiple datasets. We further show that many neural nodes dynamically shift representations between threat and safety. Our results establish reproducible decoders that integrate neural circuits, merging the well-characterized 'threat circuit' with sensory and cognitive nodes, discriminating threat from safety regardless of experimental designs or data acquisition parameters.

European Pediatric Cardiac Anesthesia Fellowship Program: A First Proof of Concept.

The Pediatric Cardiac Anesthesia (PCA) fellowship is a demanding training program in Europe and the United States. Successful completion of the program requires years of training in anesthesiology, a thorough understanding of cardiovascular anatomy and physiology, and extensive experience in the perioperative management of neonates and children with heart disease. In the context of the first candidate to successfully complete the PCA program in Europe, this article presents excerpts from the design and structure of the European PCA program. The PCA program is evaluated critically by both external and internal reviewers, and points are highlighted that could be included in the next version of the program.

Parental Knowledge, Attitude, and Practice Toward Children's Developmental Milestones in the Western Region of Saudi Arabia.

INTRODUCTION: Parents' ability to engage and raise their children in a safe and appropriate manner is largely influenced by their knowledge of child development and childrearing. This study aimed to evaluate the parenting and developmental milestone (MS) knowledge of Western region Saudi parents and identify the related elements that influence their knowledge. METHODS: This cross­sectional study was conducted for a period of six months. Ethical approval was duly sanctioned by the Institutional Review Board (IRB), and prior to participation, written informed consent was diligently procured from all the individuals involved in the study. In adherence to the paramount principles of privacy, rigorous measures were employed to de­identify the personal data of the participants, thereby safeguarding their confidentiality and anonymity. All research procedures were meticulously executed in strict compliance with the pertinent guidelines and regulatory standards governing research ethics. The study cohort consisted of Saudi parents from the Western Province of Saudi Arabia who had children aged up to six years and expressed a genuine willingness to participate in the research. This commitment was reaffirmed through their informed consent. Notably, the inclusion criteria for parental involvement did not impose any restrictions based on age or ethnic origin, ensuring a diverse and inclusive representation of this crucial demographic group. RESULTS: For assessing parental awareness and knowledge about children's developmental MSs, we examined a diverse sample of 873 participants, predominantly comprising females (77.00%). The age distribution revealed that a substantial portion of the respondents were below 30 (37.00%). Most respondents (62.40%) sought information from medical physicians and pediatricians. Gender had a significant effect, with males showing a lower awareness level compared to females (Beta = -0.582, 95% confidence interval (CI) [-0.890, -0.274], p-value < 0.001). Marital status demonstrated significance, where divorced individuals showed a lower awareness level than widowed participants (Beta = -1.641, 95% CI [-2.993, -0.288], p-value = 0.017). At the same time, no significant differences were found for singles or married individuals. CONCLUSION: Saudi parents lacked understanding of other parenting skills, such as a baby's personality and temperament, but they were well educated about some areas of childrearing, primarily physical safety precautions. It is advised that nurses and doctors give parenting advice to families at every step of their children's growth to educate and support them.

Functional candesartan loaded lipid nanoparticles for the control of diabetes-associated stroke: In vitro and in vivo studies.

Diabetes mellitus is a metabolic disease that raises the odds of developing stroke. Candesartan has been used to prevent stroke due to its inhibitory effects on blood pressure, angiogenesis, oxidative damage, and apoptosis. However, oral candesartan has very limited bioavailability and efficacy due to its weak solubility and slow release. The study aimed to develop a nasal formulation of candesartan-loaded liposomes containing ethanol and propylene glycol (CLEP) to improve candesartan's delivery, release, permeation, and efficacy as a potential diabetes-associated stroke treatment. Using design expert software, different CLEP formulations were prepared and evaluated in vitro to identify the optimum formulation, which. The selected optimum formulation composed of 3.3% phospholipid, 10% ethanol, and 15% propylene glycol significantly increased the release and permeation of candesartan relative to free candesartan by a factor of 1.52 and 1.47, respectively. The optimum formulation significantly reduced the infarction after stroke in rats; decreased flexion, spontaneous motor activity, and time spent in the target quadrant by 70%, 64.71%, and 92.31%, respectively, and enhanced grip strength by a ratio of 2.3. Therefore, nasal administration of the CLEP formulation could be a potential diabetes-associated stroke treatment.

A Case of a Newborn With Nemaline Myopathy From Al-Qunfudhah City, Saudi Arabia.

Nemaline myopathy is a primary skeletal muscle disorder and one of the congenital myopathies. It can be caused by mutations in at least 12 genes, with the nebulin (NEB) gene being the most common. Here, we present the first case of a neonate with nemaline myopathy from Al-Qunfudhah, Saudi Arabia. A full-term baby boy was delivered via cesarean section due to decreased fetal movement. The baby was covered with a thick meconium stain. He was born with severe distress and underwent an endotracheal tube placement. The baby presented generalized muscle weakness, hypotonia, and areflexia. Examination revealed arthrogryposis, bilateral small chin, undescended testicle, joint deformity, hip dislocation, and clubfoot. Chest examination revealed conducting sound and bilateral equal air entry. Moreover, he experienced bilateral chest wheeze and conducting sound. All laboratory tests were normal, and whole-exome sequencing revealed pathogenic homozygous splice acceptor variant NEB gene c.8889+1G˃A. The patient was first suspected to have spinal muscular atrophy as there was no previous nemaline myopathy case reported from Al-Qunfudhah. However, the typical symptoms and genetic sequencing confirmed his condition. As the society in Al-Qunfudhah is known for consanguinity, as in our case, clinicians should identify other types of myopathy as it is expected to occur in further cases.

Retraction: Colloid Cyst: A Potentially Life-Threatening Etiology of Severe Headache in a Patient With Migraine.

[This retracts the article DOI: 10.7759/cureus.18424.].

Antibody-Conjugated Polymersomes with Encapsulated Indocyanine Green J-Aggregates and High Near-Infrared Absorption for Molecular Photoacoustic Cancer Imaging.

Imaging plays a critical role in all stages of cancer care from early detection to diagnosis, prognosis, and therapy monitoring. Recently, photoacoustic imaging (PAI) has started to emerge into the clinical realm due to its high sensitivity and ability to penetrate tissues up to several centimeters deep. Herein, we encapsulated indocyanine green J (ICGJ) aggregate, one of the only FDA-approved organic exogenous contrast agents that absorbs in the near-infrared range, at high loadings up to ∼40% w/w within biodegradable polymersomes (ICGJ-Ps) composed of poly(lactide-co-glycolide-b-polyethylene glycol) (PLGA-b-PEG). The small Ps hydrodynamic diameter of 80 nm is advantageous for in vivo applications, while directional conjugation with epidermal growth factor receptor (EGFR) targeting cetuximab antibodies renders molecular specificity. Even when exposed to serum, the ∼11 nm-thick membrane of the Ps prevents dissociation of the encapsulated ICGJ for at least 48 h with a high ratio of ICGJ to monomeric ICG absorbances (i.e., I895/I780 ratio) of approximately 5.0 that enables generation of a strong NIR photoacoustic (PA) signal. The PA signal of polymersome-labeled breast cancer cells is proportional to the level of cellular EGFR expression, indicating the feasibility of molecular PAI with antibody-conjugated ICGJ-Ps. Furthermore, the labeled cells were successfully detected with PAI in highly turbid tissue-mimicking phantoms up to a depth of 5 mm with the PA signal proportional to the amount of cells. These data show the potential of molecular PAI with ICGJ-Ps for clinical applications such as tumor margin detection, evaluation of lymph nodes for the presence of micrometastasis, and laparoscopic imaging procedures.

Cost-Utility Analysis of Geriatric Assessment and Management in Older Adults With Cancer: Economic Evaluation Within 5C Trial.

PURPOSE: Geriatric assessment (GA) is a guideline-recommended approach to optimize cancer management in older adults. We conducted a cost-utility analysis alongside the 5C randomized controlled trial to compare GA and management (GAM) plus usual care (UC) against UC alone in older adults with cancer. METHODS: The economic evaluation, conducted from societal and health care payer perspectives, used a 12-month time horizon. The Canadian 5C study randomly assigned patients to receive GAM or UC. Quality-adjusted life-years (QALYs) were measured using the EuroQol five dimension-5L questionnaire and health care utilization using cost diaries and chart reviews. We evaluated the incremental net monetary benefit (INMB) for the full sample and preselected subgroups. RESULTS: A total of 350 patients were included, of whom 173 received GAM and 177 UC. At 12 months, the average QALYs per patient were 0.728 and 0.751 for GAM and UC, respectively (ΔQALY, -0.023 [95% CI, -0.076 to 0.028]). Considering a societal perspective, the total average costs (in 2021 Canadian dollars) per patient were $46,739 and $45,177 for GAM and UC, respectively (ΔCost, $1,563 [95% CI, -$6,583 to $10,403]). At a cost-effectiveness threshold of $50,000/QALY, GAM was not cost-effective compared with UC (INMB, -$2,713 [95% CI, -$11,767 to $5,801]). The INMB was positive ($2,984 [95% CI, -$7,050 to $14,179]; probability of being cost-effective, 72%) for patients treated with curative intent, but remained negative for patients treated with palliative intent (INMB, -$9,909 [95% CI, -$24,436 to $4,153]). Findings were similar considering a health care payer perspective. CONCLUSION: To our knowledge, this is the first cost-utility analysis of GAM in cancer. GAM was cost-effective for patients with cancer treated with curative but not with palliative intent. The study provides further considerations for future adoption of GAM in practice.

Mindfulness training and exercise differentially impact fear extinction neurocircuitry.

BACKGROUND: The ability to extinguish a maladaptive conditioned fear response is crucial for healthy emotional processing and resiliency to aversive experiences. Therefore, enhancing fear extinction learning has immense potential emotional and health benefits. Mindfulness training enhances both fear conditioning and recall of extinguished fear; however, its effects on fear extinction learning are unknown. Here we investigated the impact of mindfulness training on brain mechanisms associated with fear-extinction learning, compared to an exercise-based program. METHODS: We investigated BOLD activations in response to a previously learned fear-inducing cue during an extinction paradigm, before and after an 8-week mindfulness-based stress reduction program (MBSR, n = 49) or exercise-based stress management education program (n = 27). RESULTS: The groups exhibited similar reductions in stress, but the MBSR group was uniquely associated with enhanced activation of salience network nodes and increased hippocampal engagement. CONCLUSIONS: Our results suggest that mindfulness training increases attention to anticipatory aversive stimuli, which in turn facilitates decreased aversive subjective responses and enhanced reappraisal of the memory.

Design, optimization, and in vivo evaluation of invasome-mediated candesartan for the control of diabetes-associated atherosclerosis.

Atherosclerosis is an inflammatory disease characterized by the accumulation of arterial plaque. Diabetes mellitus stands out as a major risk factor for atherosclerosis. Candesartan is a potent angiotensin II receptor antagonist that enhances arterial blood flow and reduces insulin resistance. However, oral candesartan has limited activity because of its low bioavailability, water solubility, hepatic first-pass degradation, and efficacy. The current study aims to develop nasal candesartan-loaded invasome (CLI) drops to improve candesartan's permeation, release, and bioavailability as a potential treatment for diabetes-associated atherosclerosis. Design expert software was used to prepare various CLI formulations to determine the impact of the concentrations of ethanol, cineole, and phospholipid. The desirability index was used to estimate the optimized formulation composition to maximize entrapment efficiency and minimize vesicle size. The optimized formulation had a 1% ethanol concentration, a 1.5% cineole concentration, and a 2.32% phospholipid concentration. The selected optimized formulation was then tested in a rat model of diabetes and atherosclerosis to evaluate its activity. The results showed that nasal CLI drops significantly raised serum HDL levels by a ratio of 1.42 and lowered serum glucose, cholesterol, triglycerides, LDL, and VLDL levels by 69.70%, 72.22%, 36.52%, 58.0%, and 65.31%, respectively, compared with diabetic atherosclerotic rats, throwing an insight on the potential for promising anti-diabetic and anti-atherosclerotic activities. Additionally, atherosclerotic lesions were improved in rats treated with CLI, as shown in histopathology. In conclusion, the results of this investigation showed that treatment with nasal CSN-loaded invasome formulation drops prevented the initiation and progression of diabetes-associated atherosclerosis.

Facile preparation of a Ni-imidazole compound with high activity for ethylene dimerization.

A compound consisting of Ni and imidazole (Ni-imidazole) was synthesized in large quantities by a one-step co-precipitation method. The structure and stability of this Ni-imidazole were well studied by a series of characterization methods. The Ni-imidazole compound exhibited excellent catalytic properties for the dimerization of ethylene to 1-butene.

Protocol for generating embedding-free brain organoids enriched with oligodendrocytes.

In response to the scarcity of advanced in vitro models dedicated to human CNS white matter research, we present a protocol to generate neuroectoderm-derived embedding-free human brain organoids enriched with oligodendrocytes. We describe steps for neuroectoderm differentiation, development of neural spheroids, and their transferal to Matrigel. We then detail procedures for the development, maturation, and application of oligodendrocyte-enriched brain organoids. The presence of myelin-producing cells makes these organoids useful for studying human white matter diseases, such as leukodystrophy.

Characterization of the Bacterial Profile from Natural and Laboratory Glossina Populations.

Tsetse flies (Glossina spp.; Diptera: Glossinidae) are viviparous flies that feed on blood and are found exclusively in sub-Saharan Africa. They are the only cyclic vectors of African trypanosomes, responsible for human African trypanosomiasis (HAT) and animal African trypanosomiasis (AAT). In this study, we employed high throughput sequencing of the 16S rRNA gene to unravel the diversity of symbiotic bacteria in five wild and three laboratory populations of tsetse species (Glossina pallidipes, G. morsitans, G. swynnertoni, and G. austeni). The aim was to assess the dynamics of bacterial diversity both within each laboratory and wild population in relation to the developmental stage, insect age, gender, and location. Our results indicated that the bacterial communities associated with the four studied Glossina species were significantly influenced by their region of origin, with wild samples being more diverse compared to the laboratory samples. We also observed that the larval microbiota was significantly different than the adults. Furthermore, the sex and the species did not significantly influence the formation of the bacterial profile of the laboratory colonies once these populations were kept under the same rearing conditions. In addition, Wigglesworthia, Acinetobacter, and Sodalis were the most abundant bacterial genera in all the samples, while Wolbachia was significantly abundant in G. morsitans compared to the other studied species. The operational taxonomic unit (OTU) co-occurrence network for each location (VVBD insectary, Doma, Makao, and Msubugwe) indicated a high variability between G. pallidipes and the other species in terms of the number of mutual exclusion and copresence interactions. In particular, some bacterial genera, like Wigglesworthia and Sodalis, with high relative abundance, were also characterized by a high degree of interactions.

Optimizing the Heat Loss from an Insulation Material and Boundary Layer Thickness of Airflow through a Hot Plate Using Nonlinear Least-Squares Error and Linear Programming Algorithms.

Heat loss is a major challenge in heat transfer problems. Several researchers have minimized heat loss for different heat transfer cases, focusing on one optimization technique; however, not all optimization techniques are suitable for a given problem. A limited number of studies have compared different techniques for a given problem under boundary conditions and constraints. This review revisits basic heat transfer problems and identifies a promising technique for each problem to minimize heat loss. The paper considers three techniques: nonlinear least-squares error (LSE), interior point linear programming (IPLP), and genetic algorithm. Two cases are studied: 1. heat loss optimization from cylindrical insulating surfaces and 2. laminar airflow on a heated plate. The results are compared for each technique, and a suitable technique is recommended for each considered case. Nonlinear LSE is found to be most suitable for case 1. IPLP and GA are recommended for the Case 2 problem. The average thermal conductivity is found to be 0.081 W/mK. The average insulation thickness is found to be 213.25 mm. This research will act as a basis for future research to justify and implement suitable techniques for different heat transfer problems.

Combination of verteporfin-photodynamic therapy with 5-aza-2'-deoxycytidine enhances the anti-tumour immune response in triple negative breast cancer.

Introduction: Triple negative breast cancer (TNBC) is a subtype of breast cancer characterised by its high tumourigenic, invasive, and immunosuppressive nature. Photodynamic therapy (PDT) is a focal therapy that uses light to activate a photosensitizing agent and induce a cytotoxic effect. 5-aza-2'-deoxycytidine (5-ADC) is a clinically approved immunomodulatory chemotherapy agent. The mechanism of the combination therapy using PDT and 5-ADC in evoking an anti-tumour response is not fully understood. Methods: The present study examined whether a single dose of 5-ADC enhances the cytotoxic and anti-tumour immune effect of low dose PDT with verteporfin as the photosensitiser in a TNBC orthotopic syngeneic murine model, using the triple negative murine mammary tumour cell line 4T1. Histopathology analysis, digital pathology and immunohistochemistry of treated tumours and distant sites were assessed. Flow cytometry of splenic and breast tissue was used to identify T cell populations. Bioinformatics were used to identify tumour immune microenvironments related to TNBC patients. Results: Functional experiments showed that PDT was most effective when used in combination with 5-ADC to optimize its efficacy. 5-ADC/PDT combination therapy elicited a synergistic effect in vitro and was significantly more cytotoxic than monotherapies on 4T1 tumour cells. For tumour therapy, all types of treatments demonstrated histopathologically defined margins of necrosis, increased T cell expression in the spleen with absence of metastases or distant tissue destruction. Flow cytometry and digital pathology results showed significant increases in CD8 expressing cells with all treatments, whereas only the 5-ADC/PDT combination therapy showed increase in CD4 expression. Bioinformatics analysis of in silico publicly available TNBC data identified BCL3 and BCL2 as well as the following anti-tumour immune response biomarkers as significantly altered in TNBC compared to other breast cancer subtypes: GZMA, PRF1, CXCL1, CCL2, CCL4, and CCL5. Interestingly, molecular biomarker assays showed increase in anti-tumour response genes after treatment. The results showed concomitant increase in BCL3, with decrease in BCL2 expression in TNBC treatment. In addition, the treatments showed decrease in PRF1, CCL2, CCL4, and CCL5 genes with 5-ADC and 5-ADC/PDT treatment in both spleen and breast tissue, with the latter showing the most decrease. Discussion: To our knowledge, this is the first study that shows which of the innate and adaptive immune biomarkers are activated during PDT related treatment of the TNBC 4T1 mouse models. The results also indicate that some of the immune response biomarkers can be used to monitor the effectiveness of PDT treatment in TNBC murine model warranting further investigation in human subjects.

Autoimmune Lupus Enteritis with Pan Gastrointestinal Involvement in an Adult Patient with Systemic Lupus Erythematosus: Complete Response to Belimumab.

Autoimmune lupus enteritis in systemic lupus erythematosus (SLE) is a rare manifestation that comprises of gastrointestinal tract inflammation with supportive images and/or biopsy findings. We report a unique case of widespread lupus enteritis occurring late in the disease process and in isolation without additional features of active SLE but in the presence of SLE serological activity. There was no clear evidence of active mesenteric vasculitis, intestinal pseudo-obstruction, protein-losing enteropathy, or coagulopathy by imaging or histopathology. This is the first reported case of an SLE patient with pan-gastrointestinal involvement of lupus enteritis responding to Belimumab, with complete resolution of the gastrointestinal syndrome and no further recurrence of gastrointestinal events. Rapid diagnosis and prompt immunomodulatory treatment of lupus-related enteritis are critical to avoid potentially life-threatening complications.

A Call To Action: Cholangiocarcinoma in the Setting of Sustained Hepatitis C Virologic Response - Case Report and Review of Literature.

The incidence of cholangiocarcinoma, an aggressive malignancy with poor prognosis, is increasing. Hepatitis B and C have been well established as predisposing factors for this malignancy. The availability and efficacy of treatment for hepatitis C infection has led to a substantial reduction in viral hepatitis-related cholangiocarcinoma mortality. Despite treatment, the potential for developing cholangiocarcinoma continues to exist for patients with underlying cirrhosis. We present a patient who was effectively treated for hepatitis C with direct-acting antiviral therapy eight years prior. He presented with malaise, fatigue, and an unintentional weight loss of 40 pounds. Imaging revealed a metastatic malignancy, and a liver biopsy confirmed the diagnosis of cholangiocarcinoma and the absence of underlying cirrhosis in the background liver. This case highlights the persistent risk of developing cholangiocarcinoma despite achieving sustained virological response to treatment for hepatitis C. We review the associated literature and briefly discuss the predisposing conditions that might result in such an outcome. We also encourage the need for long-term surveillance for such patients and the importance of conducting more multi-center studies to identify at-risk patients and develop cost-effective screening protocols.