The novel family of Warbicin® compounds inhibits glucose uptake both in yeast and human cells and restrains cancer cell proliferation.

Many cancer cells share with yeast a preference for fermentation over respiration, which is associated with overactive glucose uptake and breakdown, a phenomenon called the Warburg effect in cancer cells. The yeast tps1Δ mutant shows even more pronounced hyperactive glucose uptake and phosphorylation causing glycolysis to stall at GAPDH, initiation of apoptosis through overactivation of Ras and absence of growth on glucose. The goal of the present work was to use the yeast tps1Δ strain to screen for novel compounds that would preferentially inhibit overactive glucose influx into glycolysis, while maintaining basal glucose catabolism. This is based on the assumption that the overactive glucose catabolism of the tps1Δ strain might have a similar molecular cause as the Warburg effect in cancer cells. We have isolated Warbicin ® A as a compound restoring growth on glucose of the yeast tps1Δ mutant, showed that it inhibits the proliferation of cancer cells and isolated structural analogs by screening directly for cancer cell inhibition. The Warbicin ® compounds are the first drugs that inhibit glucose uptake by both yeast Hxt and mammalian GLUT carriers. Specific concentrations did not evoke any major toxicity in mice but increase the amount of adipose tissue likely due to reduced systemic glucose uptake. Surprisingly, Warbicin ® A inhibition of yeast sugar uptake depends on sugar phosphorylation, suggesting transport-associated phosphorylation as a target. In vivo and in vitro evidence confirms physical interaction between yeast Hxt7 and hexokinase. We suggest that reversible transport-associated phosphorylation by hexokinase controls the rate of glucose uptake through hydrolysis of the inhibitory ATP molecule in the cytosolic domain of glucose carriers and that in yeast tps1Δ cells and cancer cells reversibility is compromised, causing constitutively hyperactive glucose uptake and phosphorylation. Based on their chemical structure and properties, we suggest that Warbicin ® compounds replace the inhibitory ATP molecule in the cytosolic domain of the glucose carriers, preventing hexokinase to cause hyperactive glucose uptake and catabolism.

MegaAppendix: a rare case of mantle cell lymphoma in an appendix presented as volvulus.

Mantle cell lymphoma (MCL), representing 5% of cases, is an aggressive B-cell non-Hodgkin lymphoma. Rarely, it can spread to other areas. This case illustrates a unique occurrence of MCL involving the appendix, leading to obstructive symptoms. Additionally, its presentation as volvulus added complexity to diagnosis and treatment. A 72-year-old man with a history of MCL came to the ER with right lower quadrant abdominal pain and nausea for 7 days. A computed tomography scan showed a swirling sign, concerning for volvulus. The patient required emergent surgery for exploratory laparotomy. Intraoperatively, the patient was found to have an enlarged appendix measuring 16.5 cm in length and 5 cm in diameter. An appendectomy was performed, and the pathology was confirmed to be MCL. This is a rare case of MCL presenting in the appendix as a volvulus, resulting in obstructive symptoms. This distinctive manifestation posed significant challenges in diagnosis and management. Appreciating such cases is pivotal for accurate diagnosis and effective medical and surgical interventions for this aggressive lymphoma subtype.

Direct inhibition of tumor hypoxia response with synthetic transcriptional repressors.

Many oncogenic transcription factors (TFs) are considered to be undruggable because of their reliance on large protein-protein and protein-DNA interfaces. TFs such as hypoxia-inducible factors (HIFs) and X-box-binding protein 1 (XBP1) are induced by hypoxia and other stressors in solid tumors and bind to unfolded protein response element (UPRE) and hypoxia-induced response element (HRE) motifs to control oncogenic gene programs. Here, we report a strategy to create synthetic transcriptional repressors (STRs) that mimic the basic leucine zipper domain of XBP1 and recognize UPRE and HRE motifs. A lead molecule, STR22, binds UPRE and HRE DNA sequences with high fidelity and competes with both TFs in cells. Under hypoxia, STR22 globally suppresses HIF1α binding to HRE-containing promoters and enhancers, inhibits hypoxia-induced gene expression and blocks protumorigenic phenotypes in triple-negative breast cancer (TNBC) cells. In vivo, intratumoral and systemic STR22 treatment inhibited hypoxia-dependent gene expression, primary tumor growth and metastasis of TNBC tumors. These data validate a novel strategy to target the tumor hypoxia response through coordinated inhibition of TF-DNA binding.

Zonation, ligand and dose dependence of S1PR1 signalling in blood and lymphatic vasculature.

AIMS: Circulating levels of sphingosine 1-phosphate (S1P), an HDL-associated ligand for endothelial cell (EC) protective S1P receptor-1 (S1PR1), are reduced in disease states associated with endothelial dysfunction. Yet as S1PR1 has high affinity for S1P and can be activated by ligand-independent mechanisms and EC-autonomous S1P production, it is unclear if relative reductions in circulating S1P impact endothelial function. It is also unclear how EC S1PR1 insufficiency, whether induced by ligand deficiency or by S1PR1-directed immunosuppressive therapy, affects different vascular subsets. METHODS AND RESULTS: We here fine-map the zonation of S1PR1 signalling in the murine blood and lymphatic vasculature, superimpose cell type-specific and relative deficiencies in S1P production to define ligand source- and dose-dependence, and correlate receptor engagement to essential functions. In naïve blood vessels, despite broad expression, EC S1PR1 engagement was restricted to resistance-size arteries, lung capillaries and high-endothelial venules (HEV). Similar zonation was observed for albumin extravasation in EC S1PR1 deficient mice, and brain extravasation was reproduced with arterial EC-selective S1pr1 deletion. In lymphatic EC, S1PR1 engagement was high in collecting vessels and lymph nodes and low in terminal capillaries that drain tissue fluids. While EC S1P production sustained S1PR1 signaling in lymphatics and HEV, hematopoietic cells provided ∼90% of plasma S1P and sustained signaling in resistance arteries and lung capillaries. S1PR1 signaling and endothelial function were both surprisingly sensitive to reductions in plasma S1P with apparent saturation around 50% of normal levels. S1PR1 engagement did not depend on sex or age, but modestly increased in arteries in hypertension and diabetes. Sphingosine kinase (Sphk)-2 deficiency also increased S1PR1 engagement selectively in arteries, which could be attributed to Sphk1-dependent S1P release from perivascular macrophages. CONCLUSIONS: This study highlights vessel subtype-specific S1PR1 functions and mechanisms of engagement and supports the relevance of S1P as circulating biomarker for endothelial function.

An Empirical Dietary Pattern Associated with the Gut Microbial Features in Relation to Colorectal Cancer Risk.

BACKGROUND & AIMS: Epidemiologic evidence for dietary influence on colorectal cancer (CRC) risk through the gut microbiome remains limited. METHODS: Leveraging 307 men and 212 women with stool metagenomes and dietary data, we characterized and validated a sex-specific dietary pattern associated with the CRC-related gut microbial signature (CRC Microbial Dietary Score [CMDS]). We evaluated the associations of CMDS with CRC risk according to Fusobacterium nucleatum, pks+Escherichia coli, and enterotoxigenic Bacteroides fragilis status in tumor tissue using Cox proportional hazards regression in the Health Professionals Follow-Up Study (1986-2018), Nurses' Health Study (1984-2020), and Nurses' Health Study II (1991-2019). RESULTS: The CMDS was characterized by high industrially processed food and low unprocessed fiber-rich food intakes. In 259,200 participants, we documented 3854 incident CRC cases over 6,467,378 person-years of follow-up. CMDS was associated with a higher risk of CRC (Ptrend < .001), with a multivariable hazard ratio (HRQ5 vs Q1) of 1.25 (95% CI, 1.13-1.39). The association remained after adjusting for previously established dietary patterns, for example, the Western and prudent diets. Notably, the association was stronger for tumoral F nucleatum-positive (HRQ5 vs Q1, 2.51; 95% CI, 1.68-3.75; Ptrend < .001; Pheterogeneity = .03, positivity vs negativity), pks+E coli-positive (HRQ5 vs Q1, 1.68; 95% CI, 0.84-3.38; Ptrend = .005; Pheterogeneity = .01, positivity vs negativity), and enterotoxigenic Bacteroides fragilis-positive CRC (HRQ5 vs Q1, 2.06; 95% CI, 1.10-3.88; Ptrend = .016; Pheterogeneity = .06, positivity vs negativity), compared with their negative counterparts. CONCLUSIONS: CMDS was associated with increased CRC risk, especially for tumors with detectable F nucleatum, pks+E coli, and enterotoxigenic Bacteroides fragilis in tissue. Our findings support a potential role of the gut microbiome underlying the dietary effects on CRC.

Aspirin Use and Incidence of Colorectal Cancer According to Lifestyle Risk.

Importance: Aspirin reduces the risk of colorectal cancer (CRC). Identifying individuals more likely to benefit from regular aspirin use for CRC prevention is a high priority. Objective: To assess whether aspirin use is associated with the risk of CRC across different lifestyle risk factors. Design, Setting, and Participants: A prospective cohort study among women in the Nurses' Health Study (1980-2018) and men in the Health Professionals Follow-Up Study (1986-2018) was conducted. Data analysis was performed from October 1, 2021, to May 22, 2023. Exposures: A healthy lifestyle score was calculated based on body mass index, alcohol intake, physical activity, diet, and smoking with scores ranging from 0 to 5 (higher values corresponding to a healthier lifestyle). Regular aspirin use was defined as 2 or more standard tablets (325 mg) per week. Main Outcome and Measures: Outcomes included multivariable-adjusted 10-year cumulative incidence of CRC, absolute risk reduction (ARR), and number needed to treat associated with regular aspirin use by lifestyle score and multivariable-adjusted hazard ratios for incident CRC across lifestyle scores. Results: The mean (SD) baseline age of the 107 655 study participants (63 957 women from the Nurses' Health Study and 43 698 men from the Health Professionals Follow-Up Study) was 49.4 (9.0) years. During 3 038 215 person-years of follow-up, 2544 incident cases of CRC were documented. The 10-year cumulative CRC incidence was 1.98% (95% CI, 1.44%-2.51%) among participants who regularly used aspirin compared with 2.95% (95% CI, 2.31%-3.58%) among those who did not use aspirin, corresponding to an ARR of 0.97%. The ARR associated with aspirin use was greatest among those with the unhealthiest lifestyle scores and progressively decreased with healthier lifestyle scores (P < .001 for additive interaction). The 10-year ARR for lifestyle scores 0 to 1 (unhealthiest) was 1.28%. In contrast, the 10-year ARR for lifestyle scores 4 to 5 (healthiest) was 0.11%. The 10-year number needed to treat with aspirin was 78 for participants with lifestyle scores 0 to 1, 164 for score 2, 154 for score 3, and 909 for scores 4 to 5. Among the components of the healthy lifestyle score, the greatest differences in ARR associated with aspirin use were observed for body mass index and smoking. Conclusions and Relevance: In this cohort study, aspirin use was associated with a greater absolute reduction in risk of CRC among individuals with less healthy lifestyles. The findings of the study suggest that lifestyle risk factors may be useful to identify individuals who may have a more favorable risk-benefit profile for cancer prevention with aspirin.

Factors Associated With Mosaicism in Human Embryos: A Retrospective Study.

Objective This study aims to identify factors associated with mosaicism in human embryos at Hung Vuong Hospital. Methods We performed a retrospective analysis of data from 2018 to 2022, approved by the Hung Vuong Hospital Ethics Committee (CS/HV/23/15). We analyzed variables such as demographic characteristics, clinical measurements, and in-vitro fertilization (IVF) cycle outcomes to investigate their relationship with embryo mosaicism. Results A total of 73 couples undergoing IVF with preimplantation genetic testing (PGT) were included in the analysis. Among 308 embryos, 98 (31.8%) were mosaic, 124 (40.3%) were euploid, and 86 (27.9%) were aneuploid. Univariable analysis revealed that female age was significantly associated with increased odds of mosaicism (odd ratio (OR) = 1.11, 95% confidence interval (CI): 1.04 - 1.19, p = 0.003). Male age demonstrated a marginal association with mosaicism (OR = 1.05, 95% CI: 1.00 - 1.11, p = 0.07). Other factors, including body mass index (BMI), anti-Mullerian hormone (AMH) levels, blood types, and sperm quality, were not significantly associated with mosaicism. In the multivariable analysis, controlling for both female and male age, female age showed a trend toward significance (OR = 1.12, 95% CI: 1.02 - 1.23, p = 0.02), while male age showed no significant effect (OR = 0.99, 95% CI: 0.92 - 1.06, p = 0.75). Conclusions The findings suggest that female age is a critical factor influencing the occurrence of mosaicism in embryos. Further research is needed to fully understand the mechanisms underlying mosaicism in human embryos.

Waterpipe Tobacco Smoking and Risk of Cancer Mortality.

Importance: There has been an increasing trend of using noncigarette products, including waterpipe tobacco (WTP), worldwide. While cigarette smoking is a well-established risk factor for numerous cancers, little is known about the association between WTP smoking and cancer mortality. Objective: To assess the association between WTP smoking and risk of cancer mortality in Vietnam. Design, Setting, and Participants: This cohort study was based on data from the Hanoi Prospective Cohort Study, an ongoing study with a median (range) follow-up of 11.0 (0.1-11.6) years for participants aged 15 years or older in Northern Vietnam from 2007 through 2019. Data were analyzed from June 1 to September 1, 2023. Exposures: Tobacco smoking and WTP smoking statuses. Main Outcomes and Measures: Overall and site-specific cancer mortality. Cox proportional regression models were used to calculate the hazard ratio (HR) and 95% CIs for the associations between WTP smoking alone, cigarette smoking alone, and dual WTP and cigarette smoking and the risk of cancer death. Results: A total of 554 cancer deaths were identified among the 39 401 study participants (mean [SD] age, 40.4 [18.8] years; 20 616 females [52.3%]). In multivariable models, compared with never smokers, ever smokers had a significantly increased risk of cancer mortality (HR, 1.87; 95% CI, 1.48-2.35). Exclusive WTP smokers had the highest risk of cancer mortality compared with never smokers (HR, 2.66; 95% CI, 2.07-3.43). Risk of cancer mortality was higher for dual smokers of WTP and cigarettes (HR, 2.06; 95% CI, 1.53-2.76) than for exclusive cigarette smokers (HR, 1.86; 95% CI, 1.41-2.45). As most smokers (95.6% [8897 of 9312]) were male, these patterns were more apparent in male participants. Compared with never smokers, exclusive WTP smoking among males was associated with an elevated risk of death from liver cancer (HR, 3.92; 95% CI, 2.25-6.85), lung cancer (HR, 3.49; 95% CI, 2.08-5.88), nasopharyngeal carcinoma (HR, 2.79; 95% CI, 1.27-6.12), and stomach cancer (HR, 4.11; 95% CI, 2.04-8.27). For exclusive WTP smokers, the risk of cancer mortality was highest among those who smoked 11 to 15 sessions per day (HR, 3.42; 95% CI, 2.03-5.75), started smoking at age 26 to 30 years (HR, 4.01; 95% CI, 2.63-6.11), smoked for 9 to 20 years (HR, 4.04; 95% CI, 2.16-7.56), and smoked 61 to 160 sessions annually (HR, 3.68; 95% CI, 2.38-5.71). For males, the risk of cancer death was lower for those who had quit smoking for more than 10 years, compared with those who quit smoking within 1 year (HR, 0.27; 95% CI, 0.11-0.66; P for trend < .001). Conclusion and Relevance: In this cohort study in Vietnam, WTP smoking alone or in combination with cigarette smoking was associated with an increased risk of cancer death due to liver cancer, lung cancer, nasopharyngeal carcinoma, and stomach cancer. A tailored program to control WTP smoking is warranted in Vietnam and low- and middle-income countries with a high prevalence of smoking and modest resources to address smoking-related issues.

Atlantoaxial dislocation due to Os odontoideum in down syndrome: Literature review and case reports.

INTRODUCTION AND IMPORTANCE: Os odontoideum is a rare condition commonly associated with atlantoaxial instability (AAI) and leading to atlantoaxial dislocation. The incidence of Os odontoideum is higher in patients with Down syndrome. Similar to odontoid fractures, atlantoaxial dislocation in patients with Os odontoideum can result in neurological deficits, disability, and even mortality. CASE PRESENTATION: We present two cases of Os odontoideum accompanied by Down syndrome. Both patients were hospitalized due to progressive tetraparesis after falls several months prior. Upon examination, the patients exhibited myelopathy and were unable to walk or stand. MRI revealed spinal stenosis at the C1-C2 level due to atlantoaxial dislocation. C1-C2 fixation using Harms' technique was performed in both cases. One case experienced a complication involving instrument failure, necessitating revision surgery. CLINICAL DISCUSSION: Due to the characteristics of transverse ligament laxity, low muscle tone, excessive joint flexibility, and cognitive impairment, children with both Down syndrome and Os odontoideum are at a high risk of disability and even mortality from spinal cord injury. Most authors recommend surgical management when patients exhibit atlantoaxial instability. Additional factors such as low bone density, cognitive impairment, and a high head-to-body ratio may increase the risk of surgical instrument failure and nonunion postoperatively in patients with Down syndrome. CONCLUSION: Os odontoideum is a cause of AAI in patients with DS. Indication of surgery in the presence of AAI helps to resolve neurological injury and prevent further deterioration. The use of a cervical collar is considered to prevent instrument failure postoperatively.

A novel missense variant located within the zinc finger domain of the GLI3 gene was identified in a Vietnamese pedigree with index finger polydactyly.

BACKGROUND: Polydactyly, particularly of the index finger, remains an intriguing anomaly for which no specific gene or locus has been definitively linked to this phenotype. In this study, we conducted an investigation of a three-generation family displaying index finger polydactyly. METHODS: Exome sequencing was conducted on the patient, with a filtration to identify potential causal variation. Validation of the obtained variant was conducted by Sanger sequencing, encompassing all family members. RESULTS: Exome analysis uncovered a novel heterozygous missense variant (c.1482A>T; p.Gln494His) at the zinc finger DNA-binding domain of the GLI3 protein within the proband and all affected family members. Remarkably, the variant was absent in unaffected individuals within the pedigree, underscoring its association with the polydactyly phenotype. Computational analyses revealed that GLI3 p.Gln494His impacts a residue that is highly conserved across species. CONCLUSION: The GLI3 zinc finger DNA-binding region is an essential part of the Sonic hedgehog signaling pathway, orchestrating crucial aspects of embryonic development through the regulation of target gene expression. This novel finding not only contributes valuable insights into the molecular pathways governing polydactyly during embryonic development but also has the potential to enhance diagnostic and screening capabilities for this condition in clinical settings.

Molecular mechanism of choline and ethanolamine transport in humans.

Human feline leukaemia virus subgroup C receptor-related proteins 1 and 2 (FLVCR1 and FLVCR2) are members of the major facilitator superfamily1. Their dysfunction is linked to several clinical disorders, including PCARP, HSAN and Fowler syndrome2-7. Earlier studies concluded that FLVCR1 may function as a haem exporter8-12, whereas FLVCR2 was suggested to act as a haem importer13, yet conclusive biochemical and detailed molecular evidence remained elusive for the function of both transporters14-16. Here, we show that FLVCR1 and FLVCR2 facilitate the transport of choline and ethanolamine across the plasma membrane, using a concentration-driven substrate translocation process. Through structural and computational analyses, we have identified distinct conformational states of FLVCRs and unravelled the coordination chemistry underlying their substrate interactions. Fully conserved tryptophan and tyrosine residues form the binding pocket of both transporters and confer selectivity for choline and ethanolamine through cation-π interactions. Our findings clarify the mechanisms of choline and ethanolamine transport by FLVCR1 and FLVCR2, enhance our comprehension of disease-associated mutations that interfere with these vital processes and shed light on the conformational dynamics of these major facilitator superfamily proteins during the transport cycle.

Sargramostim for Prophylactic Management of Gastrointestinal Immune-Related Adverse Events of Immune Checkpoint Inhibitor Therapy for Cancer.

Immune checkpoint inhibitor (ICI) therapy improves outcomes in several cancers. Unfortunately, many patients experience grade 3-4 treatment-related adverse events, including gastrointestinal (GI) toxicities which are common. These GI immune-related adverse events (irAEs) induced by ICIs present significant clinical challenges, require prompt intervention, and result in treatment delays or discontinuations. The treatment for these potentially severe and even fatal GI irAEs which include enterocolitis, severe diarrhea, and hepatitis may interfere with the anti-cancer approach. Sargramostim (glycosylated, yeast-derived, recombinant human GM-CSF) is an agent that has been used in clinical practice for more than 30 years with a well-recognized safety profile and has been studied in many therapeutic areas. The mechanism of action of sargramostim may treat moderate-to-severe GI irAEs without impairing the anti-cancer therapy. Some early data also suggest a potential survival benefit. Through the differentiation/maturation of monocytes, macrophages, and neutrophils and induction of anti-inflammatory T cell responses, GM-CSF aids in GI homeostasis, mucosal healing, and mucosal immunity. GM-CSF knockout mice are susceptible to severe colitis which was prevented with murine GM-CSF administration. For some patients with GI mucosa and immune cell function impairment, e.g., Crohn's disease, sargramostim reduces disease severity. In a prospective, randomized study (ECOG 1608), advanced melanoma patients had a reduction in grade 3-5 GI irAEs and less frequent colonic perforation in the sargramostim plus ipilimumab arm compared to ipilimumab alone. Sargramostim continues to be studied with ICIs for the prophylactic management of irAEs while also potentially providing a survival benefit.

MFSD7c functions as a transporter of choline at the blood-brain barrier.

Mutations in the orphan transporter MFSD7c (also known as Flvcr2), are linked to Fowler syndrome. Here, we used Mfsd7c knockout (Mfsd7c-/-) mice and cell-based assays to reveal that MFSD7c is a choline transporter at the blood-brain barrier (BBB). We performed comprehensive metabolomics analysis and detected differential changes of metabolites in the brains and livers of Mfsd7c-/-embryos. Particularly, we found that choline-related metabolites were altered in the brains but not in the livers of Mfsd7c-/- embryos. Thus, we hypothesized that MFSD7c regulates the level of choline in the brain. Indeed, expression of human MFSD7c in cells significantly increased choline uptake. Interestingly, we showed that choline uptake by MFSD7c is greatly increased by choline-metabolizing enzymes, leading us to demonstrate that MFSD7c is a facilitative transporter of choline. Furthermore, single-cell patch clamp analysis showed that the import of choline by MFSD7c is electrogenic. Choline transport function of MFSD7c was shown to be conserved in vertebrates, but not in yeasts. We demonstrated that human MFSD7c is a functional ortholog of HNM1, the yeast choline importer. We also showed that several missense mutations identified in patients exhibiting Fowler syndrome had abolished or reduced choline transport activity. Mice lacking Mfsd7c in endothelial cells of the central nervous system suppressed the import of exogenous choline from blood but unexpectedly had increased choline levels in the brain. Stable-isotope tracing study revealed that MFSD7c was required for exporting choline derived from lysophosphatidylcholine in the brain. Collectively, our work identifies MFSD7c as a choline exporter at the BBB and provides a foundation for future work to reveal the disease mechanisms of Fowler syndrome.

A retrospective study of endogenous endophthalmitis-related pyogenic liver abscess: An increasing complication in North Vietnam.

Introduction: Endogenous endophthalmitis-related Klebsiella pyogenic liver abscess is a rare complication of metastatic infection. In most cases, visual acuity results are often impaired, even blind, and even with aggressive treatment with topical antibiotics, the final results are unsatisfactory. The objective of this study is to retrospectively based on medical records to describe clinical features, risk factors, and visual outcomes of patients with endogenous endophthalmitis-related pyogenic liver abscesses. Methods: We reported a case series of 12 endogenous endophthalmitis-related pyogenic liver abscess patients from March 2021 to 2023. All cases of endogenous endophthalmitis were diagnosed at admission or during the hospital stay. Results: From the medical records of 588 pyogenic liver abscess patients, we found 12 cases of endogenous endophthalmitis with 2.0%. The result showed a mean age of 61.5 ± 12.0 (41-78), diabetes mellitus (7 of 12), right lobe (7 of 12), single abscess (9 of 12), and the mean largest abscess diameter of 5.8 ± 1.7 cm (3.3-9). All patients had ocular symptoms such as eye pain (9 of 12), pus discharge (3 of 12), hypopyon (1 of 12), swollen eyelids (2 of 12), and corneal edema (2 of 12), pyogenic liver abscess before endogenous endophthalmitis (10 of 12), the median interval between endogenous endophthalmitis and pyogenic liver abscess 6.1 ± 1.9 days, ocular symptoms before diagnosis endogenous endophthalmitis 4.4 ± 2.3 days. All affected eyes were injected intravitreously with ceftazidime, amikacin, and vancomycin. Two patients underwent evisceration. Conclusions: Endogenous endophthalmitis has permanent morbidity, reducing visual acuity, poor quality of life, and lacks the warning signs, so it is essential for early detection of symptoms and referral to ophthalmologists.

A case report of Cronkhite-Canada syndrome first encounterd at a hospital in northern Vietnam.

Introduction and importance: Cronkhite-Canada syndrome (CCS) is an extremely rare non-inherited syndrome first described in 1955 with only about 500 more cases reported so far. Since the aetiology of the disease remains unknown, there were no specific treatments in consensus. In many countries, CCS is a completely new condition that may confuse physicians at first encounter. Lessons should be learned from these cases by gastrointestinal specialists to be aware of this condition in any circumstances. Case presentation: The authors reported a case study of a 45-year-old Vietnamese male with CCS diagnosis, which encountered at our centre for the first time. Clinical discussion: The definitive diagnosis was provided by combining clinical characteristics, and endoscopic and histopathologic features, after excluding other causes of gastrointestinal polyposis. The patient responds to corticosteroids, proton pump inhibitors, and nutritional support right after treatment. After 1 year of treatment, his symptoms ameliorated completely although colon polyps insignificantly reduced. Conclusion: Gastroenterologists should always be aware of patients with CCS with the following symptoms: gastrointestinal hamartomatous polyps, diarrhoea, and the dermatologic triad of alopecia, hyperpigmentation, and onychodystrophy.

Favorable outcome of a histiocytic sarcoma patient treated with immune checkpoint inhibitor: a case report.

Introduction and Importance: Histiocytic sarcoma (HS) is an extremely rare malignancy in which there has been no standard treatment approach. Some preclinical studies have provided rationales for the application of immunotherapy in advanced HS. Case Presentation: The authors reported a case of a 61-year-old patient with metastatic HS who had a rapid progression on ifosfamide, carboplatin, and etoposide chemotherapy. The authors performed PD-L1 testing, which showed a strong positivity in 90% of tumor cells. The patient was then treated with pembrolizumab 200 mg every 3 weeks. He refused palliative radiotherapy. A dramatic response in all sites was recorded on the PET-CT scan after three cycles. He was maintained on pembrolizumab, reaching over 30 months without disease progression. Clinical Discussion: Recent molecular data suggests there could be a role of immunotherapy in HS. In our patient, the disease was refractory to chemotherapy and pembrolizumab has been given based on the strong PD-L1 expression. Response to immunotherapy has also been recorded in several cases with malignant histiocytic neoplasm. Conclusion: Immunotherapy might bring sustained disease remission in PD-L1 high expression HS and further studies evaluating the role of immune checkpoint inhibitor in this disease are warranted.

Clonal tracking in cancer and metastasis.

The eradication of many cancers has proven challenging due to the presence of functionally and genetically heterogeneous clones maintained by rare cancer stem cells (CSCs), which contribute to disease progression, treatment refractoriness, and late relapse. The characterization of functional CSC activity has necessitated the development of modern clonal tracking strategies. This review describes viral-based and CRISPR-Cas9-based cellular barcoding, lineage tracing, and imaging-based approaches. DNA-based cellular barcoding technology is emerging as a powerful and robust strategy that has been widely applied to in vitro and in vivo model systems, including patient-derived xenograft models. This review also highlights the potential of these methods for use in the clinical and drug discovery contexts and discusses the important insights gained from such approaches.

Impact of interventions on the quality of life of cancer patients: a systematic review and meta-analysis of longitudinal research.

The impact of cancer interventions has been conducted in several research due to the significant burden of this non-communicable disease. The interventions that played an important role in the improvement of the patient's quality of life (QoL) and health-related quality of life (HRQL) can be classified into two main groups: pharmaceutical and non-pharmacological methods. However, studies so far often analyze a specific group of interventions for specific types of cancer. Thus, in this systematic review and meta-analysis, we synthesized the overall impact of cancer interventions on patients' quality of life in several cancers.In this research, we followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) to search the longitudinal original research on the Web of Science (WOS) database. After that, the Newcastle-Ottawa Scale (NOS) and Jadad Scale were used to assess the quality of non-randomized control trials and randomized control trials, respectively. Then, the characteristics of the included studies were described in the six main fields table and the random effect model with robust estimation was applied to analyze the impact of interventions on the health utility of patients.From the database, 122 longitudinal original research were included in the meta-regression, with most of them having high or fair quality. The European Organization for the research and treatment of cancer scale for quality of life (EORTC-QLQ) was the most used health utility measurement at 65.15%. In the adjusted effect models, the Visual Analogue Scale (VAS) had significant statistics in all models when we compared it with the EQ-5D Scale (p < 0.05) and several types of cancer such as breast, lung, and prostate cancer had significant statistics when comparing with hematological cancer in the model types of cancer (p < 0.01). Moreover, radiotherapy, screening, and a combination of chemotherapy and best supportive care also had significant statistics (p < 0.01) in the model of interventions when compared with radiotherapy applied only. Our research can suggest a vital combination of both pharmaceutical and non-pharmacological interventions to improve the quality of life of some common types of cancer patients.

1 Year-follow-up of transforaminal surgical approach in the management of migrated disc herniation: a cross-sectional study.

Transforaminal percutaneous endoscopic lumbar discectomy (TPELD) recently confirms its superiority compared to typical open discectomy in the treatment of very high-grade migrated disk herniation. In Vietnam, this technique has been applied in recent years; however; lack of reports and evidence. Objectives: In this study, the authors would like to share their surgical experience and report the initial results in their center, after successfully performing TPELD for very high-grade migrated disk herniation in 40 patients. Patients and methods: Forty patients, who underwent TPELD to remove the nucleus of very high-grade migrated disk herniation, were enrolled in this study. The study was carried out from April 2019 to April 2021. Preoperative and postoperative MRI were compared to demonstrate the removed disk. Postoperative visual analog score, oswestry disability index, and modified Macnab criteria were obtained after 1 month, 6 months, and 1 year and were compared. Results: There were no major complications related directly to this technique. Seven patients were operated at L3-4, 28 patients at L4-5, and 5 patients at l5-S1. Mean visual analog score for leg pain improved from 7.36±0.64 preoperatively to 1.22±1.16 at 6 months postoperatively and 1.34±1.47 at 1 year postoperatively (P<0.01). The mean preoperative oswestry disability index improved from 67.1±8.79 preoperatively to 12.1±13.48 at 1 year postoperatively (P<0.01). Excellent or good global outcomes were obtained in 95%. Conclusions: TPELD is a minimally invasive treatment with effective and safe results of very high-grade migrated disk herniation. Improvement of several pain scores can be observed in the 12-month follow-up after surgery.