Proteomic characterization of Tenacibaculum dicentrarchi under iron limitation reveals an upregulation of proteins related to iron oxidation and reduction metabolism, iron uptake systems and gliding motility.

A strategy for vaccine design involves identifying proteins that could be involved in pathogen-host interactions. The aim of this proteomic study was to determine how iron limitation affects the protein expression of Tenacibaculum dicentrarchi, with a primary focus on virulence factors and proteins associated with iron uptake. The proteomic analysis was carried out using two strains of T. dicentrarchi grown under normal (control) and iron-limited conditions, mimicking the host environment. Our findings revealed differences in the proteins expressed by the type strain CECT 7612T and the Chilean strain TdCh05 of T. dicentrarchi. Nonetheless, both share a common response to iron deprivation, with an increased expression of proteins associated with iron oxidation and reduction metabolism (e.g., SufA, YpmQ, SufD), siderophore transport (e.g., ExbD, TonB-dependent receptor, HbpA), heme compound biosynthesis, and iron transporters under iron limitation. Proteins involved in gliding motility, such as GldL and SprE, were also upregulated in both strains. A negative differential regulation of metabolic proteins, particularly those associated with amino acid biosynthesis, was observed under iron limitation, reflecting the impact of iron availability on bacterial metabolism. Additionally, the TdCh05 strain exhibited unique proteins associated with gliding motility machinery and phage infection control compared to the type strain. These groups of proteins have been identified as virulence factors within the Flavobacteriaceae family, including the genus Tenacibaculum. These results build upon our previous report on iron acquisition mechanisms and could lay the groundwork for future studies aimed at elucidating the role of some of the described proteins in the infectious process of tenacibaculosis, as well as in the development of potential vaccines.

Seasonal dietary changes relate to gut microbiota composition depending on the host species but do not correlate with gut microbiota diversity in arthropod-eating lizards.

The animal gut microbiota is strongly influenced by environmental factors that shape their temporal dynamics. Although diet is recognized as a major driver of gut microbiota variation, dietary patterns have seldom been linked to gut microbiota dynamics in wild animals. Here, we analysed the gut microbiota variation between dry and rainy seasons across four Sceloporus species (S. aeneus, S. bicanthalis, S. grammicus and S. spinosus) from central Mexico in light of temporal changes in diet composition. The lizard microbiota was dominated by Firmicutes (now Bacillota) and Bacteroidota, and the closely related species S. aeneus and S. bicanthalis shared a great number of core bacterial taxa. We report species-specific seasonal changes in gut microbiota diversity and composition: greater alpha diversity during the dry compared to the rainy season in S. bicanthalis, the opposite pattern in S. aeneus, and no seasonal differences in S. grammicus and S. spinosus. Our findings indicated a positive association between gut bacterial composition and dietary composition for S. bicanthalis and S. grammicus, but bacterial diversity did not increase linearly with dietary richness in any lizard species. In addition, seasonality affected bacterial composition, and microbial community similarity increased between S. aeneus and S. bicanthalis, as well as between S. grammicus and S. spinosus. Together, our results illustrate that seasonal variation and dietary composition play a role in shaping gut microbiota in lizard populations, but this is not a rule and other ecological factors influence microbiota variation.

Discovery and Characterization of the ddx41 Gene in Atlantic Salmon: Evolutionary Implications, Structural Functions, and Innate Immune Responses to Piscirickettsia salmonis and Renibacterium salmoninarum Infections.

The innate immune response in Salmo salar, mediated by pattern recognition receptors (PRRs), is crucial for defending against pathogens. This study examined DDX41 protein functions as a cytosolic/nuclear sensor for cyclic dinucleotides, RNA, and DNA from invasive intracellular bacteria. The investigation determined the existence, conservation, and functional expression of the ddx41 gene in S. salar. In silico predictions and experimental validations identified a single ddx41 gene on chromosome 5 in S. salar, showing 83.92% homology with its human counterpart. Transcriptomic analysis in salmon head kidney confirmed gene transcriptional integrity. Proteomic identification through mass spectrometry characterized three unique peptides with 99.99% statistical confidence. Phylogenetic analysis demonstrated significant evolutionary conservation across species. Functional gene expression analysis in SHK-1 cells infected by Piscirickettsia salmonis and Renibacterium salmoninarum indicated significant upregulation of DDX41, correlated with increased proinflammatory cytokine levels and activation of irf3 and interferon signaling pathways. In vivo studies corroborated DDX41 activation in immune responses, particularly when S. salar was challenged with P. salmonis, underscoring its potential in enhancing disease resistance. This is the first study to identify the DDX41 pathway as a key component in S. salar innate immune response to invading pathogens, establishing a basis for future research in salmonid disease resistance.

Inorganic Polyphosphate Affects Biofilm Assembly, Capsule Formation, and Virulence of Hypervirulent ST23 Klebsiella pneumoniae.

The emergence of hypervirulent Klebsiella pneumoniae (hvKP) strains poses a significant threat to public health due to high mortality rates and propensity to cause severe community-acquired infections in healthy individuals. The ability to form biofilms and produce a protective capsule contributes to its enhanced virulence and is a significant challenge to effective antibiotic treatment. Polyphosphate kinase 1 (PPK1) is an enzyme responsible for inorganic polyphosphate synthesis and plays a vital role in regulating various physiological processes in bacteria. In this study, we investigated the impact of polyP metabolism on the biofilm and capsule formation and virulence traits in hvKP using Dictyostelium discoideum amoeba as a model host. We found that the PPK1 null mutant was impaired in biofilm and capsule formation and showed attenuated virulence in D. discoideum compared to the wild-type strain. We performed a proteomic analysis to gain further insights into the underlying molecular mechanism. The results revealed that the PPK1 mutant had a differential expression of proteins involved in capsule synthesis (Wzi-Ugd), biofilm formation (MrkC-D-H), synthesis of the colibactin genotoxin precursor (ClbB), as well as proteins associated with the synthesis and modification of lipid A (ArnB-LpxC-PagP). These proteomic findings corroborate the phenotypic observations and indicate that the PPK1 mutation is associated with impaired biofilm and capsule formation and attenuated virulence in hvKP. Overall, our study highlights the importance of polyP synthesis in regulating extracellular biomolecules and virulence in K. pneumoniae and provides insights into potential therapeutic targets for treating K. pneumoniae infections.

Are Medium Cut-off Membranes the Future, or the Promising Reality for Chronic Hemodialysis Patients?

ABSTRACT The development of hemodialysis (HD) membranes has substantially advanced in the last decade. This has resulted in the manufacturing of medium cut-off membranes (MCO) whose internal architecture is based on greater pore size and a smaller diameter, thus promoting the clearance of particles of greater size as well as retrofiltration. Multiple studies have proven their efficacy in the clearance of uremic mid-sized molecules such as β2-microglobulin, free light chains, and some interleukins; this clearance is far superior with MCO membranes when compared with high-flux HD, and similar to that obtained with online hemodiafiltration. This review summarizes the results of the most relevant clinical studies of this membrane in terms of uremic toxin clearance, as well as the features of some clinical outcomes such as quality of life and hospitalizations.

Are medium cut-off membranes the future, or the promising reality for chronic hemodialysis patients?

The development of hemodialysis (HD) membranes has substantially advanced in the last decade. This has resulted in the manufacturing of medium cut-off membranes (MCO) whose internal architecture is based on greater pore size and a smaller diameter, thus promoting the clearance of particles of greater size as well as retrofiltration. Multiple studies have proven their efficacy in the clearance of uremic mid-sized molecules such as ß2-microglobulin, free light chains, and some interleukins; this clearance is far superior with MCO membranes when compared with high-flux HD, and similar to that obtained with online hemodiafiltration. This review summarizes the results of the most relevant clinical studies of this membrane in terms of uremic toxin clearance, as well as the features of some clinical outcomes such as quality of life and hospitalizations.

Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome.

Introduction: Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main pathways and long-term consequences attributed to this condition by analyzing clinical parameters and functional tests supported by machine learning and serum proteome profiling. Methods: Patients with L-TPD were classified according to the results of their computer-tomography (CT) scan and diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLCOc) tests at 4 and 12-months post-infection. Results: Regarding the acute phase, our data showed that L-TPD was favored in elderly patients with hypertension or insulin resistance, supported by pathways associated with vascular inflammation and chemotaxis of phagocytes, according to computer proteomics. Then, at 4-months post-infection, clinical and functional tests revealed that L-TPD patients exhibited a restrictive lung condition, impaired aerobic capacity and reduced muscular strength. At this time point, high circulating levels of platelets and CXCL9, and an inhibited FCgamma-receptor-mediated-phagocytosis due to reduced FcγRIII (CD16) expression in CD14+ monocytes was observed in patients with L-TPD. Finally, 1-year post infection, patients with L-TPD worsened metabolic syndrome and augmented body mass index in comparison with other patient groups. Discussion: Overall, our data demonstrated that CT scan and DLCOc identified patients with L-TPD after COVID-19. This condition was associated with vascular inflammation and impair phagocytosis of virus-antibody immune complexes by reduced FcγRIII expression. In addition, we conclude that COVID-19 survivors required a personalized follow-up and adequate intervention to reduce long-term sequelae and the appearance of further metabolic diseases.

Bayesian Analysis Used to Identify Clinical and Laboratory Variables Capable of Predicting Progression to Severe Dengue among Infected Pediatric Patients.

The current contribution aimed to evaluate the capacity of the naive Bayes classifier to predict the progression of dengue fever to severe infection in children based on a defined set of clinical conditions and laboratory parameters. This case-control study was conducted by reviewing patient files in two public hospitals in an endemic area in Mexico. All 99 qualifying files showed a confirmed diagnosis of dengue. The 32 cases consisted of patients who entered the intensive care unit, while the 67 control patients did not require intensive care. The naive Bayes classifier could identify factors predictive of severe dengue, evidenced by 78% sensitivity, 91% specificity, a positive predictive value of 8.7, a negative predictive value of 0.24, and a global yield of 0.69. The factors that exhibited the greatest predictive capacity in the model were seven clinical conditions (tachycardia, respiratory failure, cold hands and feet, capillary leak leading to the escape of blood plasma, dyspnea, and alterations in consciousness) and three laboratory parameters (hypoalbuminemia, hypoproteinemia, and leukocytosis). Thus, the present model showed a predictive and adaptive capacity in a small pediatric population. It also identified attributes (i.e., hypoalbuminemia and hypoproteinemia) that may strengthen the WHO criteria for predicting progression to severe dengue.

Evaluation of hemodialysis vascular access. Perspective from Mexico.

Chronic kidney disease (CKD) has become a global health problem. In 2019, it was related to 2.53% of general global mortality (2.35-2.66%); in the same year, in Latin America, mortality related to CKD reached 5.25% (4.92-5.49%), with an annual increase of 3.37%, proving increased mortality of 102% between 1990 and 2017. A nephrology specialty in Mexico recently fulfilled its first 50 years. Despite being relatively young, nephrologists are interested in "new" sub-specialties of nephrology and learning novel techniques and problem-solving skills. Our group is the first in our country to focus solely and exclusively on comprehensive VA care and we want to position ourselves as the first Mexican interdisciplinary group focused on vascular access (GIMEXAV).

DNA metabarcoding reveals seasonal changes in diet composition across four arthropod-eating lizard species (Phrynosomatidae: Sceloporus).

Diet composition and its ecological drivers are rarely investigated in coexisting closely related species. We used a molecular approach to characterize the seasonal variation in diet composition in four spiny lizard species inhabiting a mountainous ecosystem. DNA metabarcoding revealed that the lizards Sceloporus aeneus, S. bicanthalis, S. grammicus, and S. spinosus mostly consumed arthropods of the orders Hemiptera, Araneae, Hymenoptera, and Coleoptera. The terrestrial lizards S. aeneus and S. bicanthalis mostly predated ants and spiders, whereas the arboreal-saxicolous S. grammicus and saxicolous S. spinosus largely consumed grasshoppers and leafhoppers. The taxonomic and phylogenetic diversity of the prey was higher during the dry season than the rainy season, likely because reduced prey availability in the dry season forced lizards to diversify their diets to meet their nutritional demands. Dietary and phylogenetic composition varied seasonally depending on the species, but only dietary composition varied with altitude. Seasonal dietary turnover was greater in S. spinosus than in S. bicanthalis, suggesting site-specific seasonal variability in prey availability; no other differences among species were observed. S. bicanthalis, which lives at the highest altitude in our study site, displayed interseasonal variation in diet breadth. Dietary differences were correlated with the species' feeding strategies and elevational distribution, which likely contributed to the coexistence of these lizard species in the studied geographic area and beyond.

Improved ß2-Microglobulin and Phosphorous Removal with Expanded Hemodialysis and Online Hemodiafiltration versus High-Flux Hemodialysis: A Cross-Over Randomized Clinical Trial.

INTRODUCTION: Expanded hemodialysis (HDx) is expected to provide enhanced permeability of medium-sized molecules, selective solute retention, and better internal retrofiltration. The primary objective of this study was to compare the efficiency for removal of ß2-microglobulin with 3 different extracorporeal therapies (ETs): high-flux hemodialysis (HF), online hemodiafiltration (OL-HDF), and HDx. The secondary objective was to evaluate the efficiency of removal of other uremic toxins, including urea, phosphate, CRP, IL-6, IL-10, TNF-⍺, indoxyl sulfate, and p-cresol. METHODS: This single-center, randomized, and cross-over study was performed. Patients were randomized to determine the initial modality of treatment, each period lasted 4 weeks and between one modality and another, there was a washout period of 1 week. Reduction ratios (RRs) of different-size molecules and albumin were calculated for the different ET. RESULTS: Twenty-two patients were included, ß2-microglobulin RR was greater during both OL-HDF and HDx as compared to HF (RR 62% vs. 73% vs. 27%, respectively, p = <0.0001), and there was no significant difference between HDx and OL-HDF (p = 0.09). A decrease in serum phosphate levels was observed in the HDx and OL-HDF periods, contrary to an increase in HF (-0.79 mg/dL vs. -1.02 mg/dL vs. + 0.11 mg/dL, respectively, p = <0.0001). There was no difference in RRs of other molecules (BUN, CRP, IL-6, IL-10, TNF-⍺, indoxyl sulfate, and p-Cresol). There was no decrease in serum albumin in any ET. CONCLUSION: HDx provides enhanced removal of ß2-microglobulin and phosphate as compared to HF, and similar efficacy as with OL-HDF. HDx should be considered an alternative to chronic convective therapies.

Osteosynthesis of a patellar fracture with repair of the knee extensor mechanism: Case report.

Patella fractures correspond to 1 % of all fractures. In recent decades, the role of the patella in increasing the lever arm of the quadriceps has been well defined. Surgical treatment is indicated for open fractures, those that compromise the function of the extensor mechanism, those with a joint gap >5 mm and/or joint incongruity >3 mm, a group that corresponds to around 30 % of the total. Anatomical reduction and stabilization with various types of modified tension bands is the most frequently used procedure. Biomechanical studies have shown that stabilization through the use of a tension band replacing the Kirchner wires with cannulated screws presents adequate resistance to fracture displacement and provides greater stability than the classic configuration, maintaining the theoretical principle of converting the forces of anterior tension of the patella generated by the quadriceps in compression at the level of the articular surface. A case of a patient who required reduction and osteosynthesis of an exposed patella fracture, associated with an extensor mechanism lesion, is presented. Clinical and radiographic characteristics of the patient and the resolution of the case are described.

Proteomic and toxicological analysis of the response of dinoflagellate Alexandrium catenella to changes in NaNO3 concentration.

Dinoflagellates of the genus Alexandrium cause Harmful Algal Blooms (HABs) in coastal waters worldwide, damaging marine environments, aquaculture, and human health. They synthesize potent neurotoxic alkaloids known as PSTs (i.e., Paralytic Shellfish Toxins), the etiological agents of PSP (i.e., Paralytic Shellfish Poisoning). In recent decades, the eutrophication of coastal waters with inorganic nitrogen (e.g., nitrate, nitrite, and ammonia) has increased the frequency and scale of HABs. PSTs concentrations within Alexandrium cells can increase by up to 76% after a nitrogen enrichment event; however, the mechanisms that underlie their biosynthesis in dinoflagellates remains unclear. This study combines mass spectrometry, bioinformatics, and toxicology and investigates the expression profiles of PSTs in Alexandrium catenella grown in 0.4, 0.9 and 1.3 mM NaNO3. Pathway analysis of protein expression revealed that tRNA amino acylation, glycolysis, TCA cycle and pigment biosynthesis were upregulated in 0.4 mM and downregulated in 1.3 mM NaNO3 compared to those grown in 0.9 mM NaNO3. Conversely, ATP synthesis, photosynthesis and arginine biosynthesis were downregulated in 0.4 mM and upregulated in 1.3 mM NaNO3. Additionally, the expression of proteins involved in PST biosynthesis (sxtA, sxtG, sxtV, sxtW and sxtZ) and overall PST production like STX, NEO, C1, C2, GTX1-6 and dcGTX2 was higher at lower nitrate concentrations. Therefore, increased nitrogen concentrations increase protein synthesis, photosynthesis, and energy metabolism and decrease enzyme expression in PST biosynthesis and production. This research provides new clues about how the changes in the nitrate concentration can modulate different metabolic pathways and the expression of PST biosynthesis in toxigenic dinoflagellates.

Importance of Confirmatory Tests for Sars-Cov-2 Infection in Hemodialysis Patients: A Multicenter Mexican Registry

Abstract Background: Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, patients with chronic kidney disease vulnerable to suffering more severe COVID-19 disease and worse outcomes have been identified Objectives: Our study's aim was to determine the incidence, characteristics, and outcomes of SARS-CoV-2 infection in patients of hemodialysis (HD) units in Mexico and to describe the availability of confirmatory testing Methods: This study was multicentric study of 19 HD units, conducted between March 2020 and March 2021 Results: From a total of 5779 patients, 955 (16.5%) cases of suspicious COVID-19 were detected; a SARS-CoV-2 reverse transcription polymerase chain reaction test was done in only 50.6% of patients. Forty-five percentages were hospitalized and 6% required invasive mechanical ventilation (IMV). There was no significant difference in mortality between confirmed (131/483) and suspicious (124/472) cases (p = 0.74). The percentage of patients in need of hospitalization, IMV, and deceased was greater than in the rest of the study population Conclusions: The study revealed that 49.4% of the cases were not confirmed, a worrisome observation given that this is a highly vulnerable population (higher probability of contagion and worse outcomes), in which 100% of patients should have a confirmatory test

Comparative analysis of two nonlethal methods for the study of the gut bacterial communities in wild lizards.

Fecal samples or cloacal swabs are preferred over lethal dissections to study vertebrate gut microbiota for ethical reasons, but it remains unclear which nonlethal methods provide more accurate information about gut microbiota. We compared the bacterial communities of three gastrointestinal tract (GIT) segments, that is, stomach, small intestine (midgut), and rectum (hindgut) with the bacterial communities of the cloaca and feces in the mesquite lizard Sceloporus grammicus. The hindgut had the highest taxonomic and functional alpha diversity, followed by midgut and feces, whereas the stomach and cloaca showed the lowest diversities. The taxonomic assemblages of the GIT segments at the phylum level were strongly correlated with those retrieved from feces and cloacal swabs (rs > 0.84 in all cases). The turnover ratio of Amplicon Sequence Variants (ASVs) between midgut and hindgut and the feces was lower than the ratio between these segments and the cloaca. More than half of the core-ASVs in the midgut (24 of 32) and hindgut (58 of 97) were also found in feces, while less than 5 were found in the cloaca. At the ASVs level, however, the structure of the bacterial communities of the midgut and hindgut were similar to those detected in feces and cloaca. Our findings suggest that fecal samples and cloacal swabs of spiny lizards provide a good approximation of the taxonomic assemblages and beta diversity of midgut and hindgut microbiota, while feces better represent the bacterial communities of the intestinal segments at a single nucleotide variation level than cloacal swabs.

What Did We Learn about Coronavirus Disease-19-Associated Acute Kidney Injury During the Pandemic?

ABSTRACT Initial reports suggested that kidney involvement after coronavirus disease 19 (COVID-19) infection was uncommon, but this premise appears to be incorrect. Acute kidney injury can occur through various mechanisms and complicate the course of up to 25% of patients with COVID-19 hospitalized in our Institution, and of over 50% of those on invasive mechanical ventilation. Mechanisms of injury include direct kidney injury and predominantly tubular, although glomerular injury has been reported, and resulting from severe hypoxic respiratory failure, secondary infection, and exposure to nephrotoxic drugs. The mainstay of treatment remains the prevention of progressive kidney damage and, in some cases, the use of renal replacement therapy. Although the use of blood purification techniques has been proposed as a potential treatment, results to date have not been conclusive. In this manuscript, the mechanisms of kidney injury by COVID-19, risk factors, and the mainstays of treatment are reviewed.

What did we learn about coronavirus disease-19-associated acute kidney injury during the pandemic?

Initial reports suggested that kidney involvement after coronavirus disease 19 (COVID-19) infection was uncommon, but this premise appears to be incorrect. Acute kidney injury can occur through various mechanisms and complicate the course of up to 25% of patients with COVID-19 hospitalized in our Institution, and of over 50% of those on invasive mechanical ventilation. Mechanisms of injury include direct kidney injury and predominantly tubular, although glomerular injury has been reported, and resulting from severe hypoxic respiratory failure, secondary infection, and exposure to nephrotoxic drugs. The mainstay of treatment remains the prevention of progressive kidney damage and, in some cases, the use of renal replacement therapy. Although the use of blood purification techniques has been proposed as a potential treatment, results to date have not been conclusive. In this manuscript, the mechanisms of kidney injury by COVID-19, risk factors, and the mainstays of treatment are reviewed.

Analysis of Tumor-Infiltrating T-Cell Transcriptomes Reveal a Unique Genetic Signature across Different Types of Cancer.

CD8+ and CD4+ T-cells play a key role in cellular immune responses against cancer by cytotoxic responses and effector lineages differentiation, respectively. These subsets have been found in different types of cancer; however, it is unclear whether tumor-infiltrating T-cell subsets exhibit similar transcriptome profiling across different types of cancer in comparison with healthy tissue-resident T-cells. Thus, we analyzed the single cell transcriptome of five tumor-infiltrating CD4-T, CD8-T and Treg cells obtained from different types of cancer to identify specific pathways for each subset in malignant environments. An in silico analysis was performed from single-cell RNA-sequencing data available in public repositories (Gene Expression Omnibus) including breast cancer, melanoma, colorectal cancer, lung cancer and head and neck cancer. After dimensionality reduction, clustering and selection of the different subpopulations from malignant and nonmalignant datasets, common genes across different types of cancer were identified and compared to nonmalignant genes for each T-cell subset to identify specific pathways. Exclusive pathways in CD4+ cells, CD8+ cells and Tregs, and common pathways for the tumor-infiltrating T-cell subsets were identified. Finally, the identified pathways were compared with RNAseq and proteomic data obtained from T-cell subsets cultured under malignant environments and we observed that cytokine signaling, especially Th2-type cytokine, was the top overrepresented pathway in Tregs from malignant samples.

Proteogenomic analysis in an early onset diffuse gastric cancer patient revealed alterations in PIK3R1, TP53, SMAD4 and a potential role of the PI3K-AKT and EGFR pathways: a case report.

Background: Early-onset gastric cancers (EOGC) are poor prognosis hard-to treat malignancies that affect young individuals (<45 years old). Case Description: Herein we describe the case of a 26-year-old female EOGC patient that initially displayed stable disease after first-line CAPOX plus immunotherapy. However, patient eventually developed progressive disease and was consecutively switched to paclitaxel plus ramucirumab, and palliative irinotecan. In search for therapeutic alternatives a proteo-genomic analysis was performed in a tissue biopsy taken after the first progression. Our analyses found a total of 18 somatic mutations, including TP53 and PIK3R1, and a previously unreported germline alteration in the tumor suppressor SMAD4. Also, our proteomic analysis found 62 proteins previously documented as "enriched in stomach cancer" and AKT/mTOR and EGFR as pathways with therapeutic potential. Unfortunately, the clinical utility of AKT/mTOR inhibitors or EGFR targeted therapies could not be assessed. Conclusions: As explained above EOGC is a growing health concern that affects young individuals. Furthermore, the reported case displayed a poor response to standard therapy including checkpoint inhibitors and chemotherapy despite the presence of biomarkers that predict a favorable outcome. Future studies should adopt alternative approaches to find novel, more effective therapies.