Taurine: a promising nutraceutic in the prevention of retinal degeneration

Taurine is considered a non-essential amino acid because it is synthesized by most mammals.However,dietary intake of taurine may be necessary to achieve the physiological levels required for the development,maintenance,and function of certain tissues.Taurine may be especially important for the retina.The concentration of taurine in the retina is higher than that in any other tissue in the body and taurine deficiency causes retinal oxidative stress,apoptosis,and degeneration of photoreceptors and retinal ganglion cells.Low plasma taurine levels may also underlie retinal degeneration in humans and therefore,taurine administration could exert retinal neuroprotective effects.Taurine has antioxidant,anti-apoptotic,immunomodulatory,and calcium homeostasis-regulatory properties.This review summarizes the role of taurine in retinal health and disease,where it appears that taurine may be a promising nutraceutical.

Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.

Oligodendroctyes:the forgotten players of diabetes pathophysiology

Oligodendrocytes(OLs),glial cells that provide myelin sheaths to axons in the central nervous system(CNS),have a dual role.First,this myelin fatty cover around the axons protects the nerves and is crucial for the saltatory propagation of action potentials.Second and not less important,OLs provide trophic support to neurons and axons.Thus,OL metabolism is important for OL well-being and the proper accomplishment of their functions,and OL metabolism energetics directly affect the energy metabolism of neighboring neurons.

A texture-modified dessert with high nutritional value designed for people with dysphagia:effect of refrigeration and frozen storage

Dysphagia is commonly associated with malnutrition and an increased choking risk.To overcome these complications,food designed for people with dysphagia should have an appropriate texture and a high nutritional value.In this study,six formulations of a strawberry dessert enriched in protein(calcium caseinate)and fiber(wheat dextrin or inulin)were developed using different hydrocolloids(xanthan gum,carboxymethyl cellulose or modified starch)to provide desirable texture and stability.Nutritional value was calculated and total phenolic content and antioxidant activity of the samples were analyzed.Back-extrusion test,rheological measurements and sensory analysis were performed in refrigerated and frozen samples to characterize their textural and viscoelastic properties.The high content in protein(14.7 g/100 g)and fiber(7.9-8.7 g/100 g)made possible to use the claims“high protein”and“high fiber”.Phytochemicals supplied by strawberries contributed to the antioxidant properties of the dessert.Loss tangent ranged 0.28-0.35 for all the formulations,indicating a weak gel behavior,which could be considered safe to swallow.The formulations with dextrin in combination with carboxymethyl cellulose or xanthan gum seemed to be less susceptible to structural changes during frozen storage.This work provides insights for the development of a nutrient-dense dessert that meets the requirements of people with dysphagia.

Targeting epidermal growth factor receptor signaling to facilitate cortical injury repair?

The existence of neural stem cells(NSC)in specific areas of the adult mammalian brain leads to the generation of new neurons involved in homeostatic mechanisms.This is the case of the NSC of the subventricular zone(SVZ)that produces olfactory bulb(OB)neurons.These neurons integrate into circuits to modulate sensory information and participate in olfactory processing(Bragado Alonso et al.,2019).A series of hierarchical events need to take place to produce OB neurons from NSC of the SVZ.First,the activation of quiescent NSC is necessary to produce intermediate transit amplifying progenitors(TAP),which will generate neuroblasts.The latter are cells that maintain a proliferative phenotype while in an immature phase.However,once they initiate migration toward the OB,they progressively undergo their differentiation into neurons(Kjell et al.,2020).

Vortex Quantum Droplets under Competing Nonlinearities

This concise review summarizes recent advancements in theoretical studies of vortex quantum droplets(VQDs)in matter-wave fields.These are robust self-trapped vortical states in two-and three-dimensional(2D and 3D)Bose–Einstein condensates(BECs)with intrinsic nonlinearity.Stability of VQDs is provided by additional nonlinearities resulting from quantum fluctuations around mean-field states,often referred to as the Lee–Huang–Yang(LHY)corrections.The basic models are presented,with emphasis on the interplay between the mean-field nonlinearity,LHY correction,and spatial dimension,which determines the structure and stability of VQDs.We embark by delineating fundamental properties of VQDs in the 3D free space,followed by consideration of their counterparts in the 2D setting.Additionally,we address stabilization of matter-wave VQDs by optical potentials.Finally,we summarize results for the study of VQDs in the single-component BEC of atoms carrying magnetic moments.In that case,the anisotropy of the long-range dipole-dipole interactions endows the VQDs with unique characteristics.The results produced by the theoretical studies in this area directly propose experiments for the observation of novel physical effects in the realm of quantum matter,and suggest potential applications to the design of new schemes for processing classical and quantum information.

Routine invasive strategy and frailty burden in non-ST-segment elevation acute myocardial infarction

Objective To assess the prognostic impact of a routine invasive strategy according to the frailty burden in patients with non-ST-segment elevation myocardial infarction(NSTEMI)from the MOSCA-FRAIL clinical trial.Methods The MOSCA-FRAIL trial randomized 167 frail patients,defined by a Clinical Frailty Scale(CFS)≥4,with NSTEMI to an invasive or conservative strategy.The primary endpoint was the number of days alive and out of hospital(DAOH)one year after discharge.For this subanalysis,we compared the impact of an invasive strategy on the outcomes between vulnerable(CFS=4,n=43)and frail(CFS>4,n=124)patients.Results Compared to vulnerable patients,frail patients presented lower values of DAOH(289.8 vs.320.6,P=0.146),more read-missions(1.03 vs.0.58,P=0.046)and higher number of days spent at the hospital during the first year(10.8 vs.3.8,P=0.014).The cau-ses of readmission were mostly non-cardiac(56%).Among vulnerable patients,DAOH were similar regardless of strategy(invasive vs.conservative:325.7 vs.314.7,P=0.684).Among frailest patients,the invasive group tended to have less DAOH(267.7 vs.311.1,P=0.117).Indeed,patients with CFS>4,invasively managed lived 29 days less than their conservative counterparts.In contrast,the-re were no differences in the subgroup with CFS=4.Conclusions Adult patients with frailty and NSTEMI showed different prognosis according to the degree of frailty.A routine in-vasive strategy does not improve outcomes and might be harmful to the frailest patients.

Woody plant taxonomic,functional,and phylogenetic diversity decrease along elevational gradients in Andean tropical montane forests:Environmental filtering and arrival of temperate taxa

Mountains are paramount for exploring biodiversity patterns due to the mosaic of topographies and climates encompassed over short distances.Biodiversity research has traditionally focused on taxonomic diversity when investigating changes along elevational gradients,but other facets should be considered.For first time,we simultaneously assessed elevational trends in taxonomic,functional,and phylogenetic diversity of woody plants in Andean tropical montane forests and explored their underlying ecological and evolutionary causes.This investigation covered four transects(traversing ca.2200 m a.s.l.) encompassing 114 plots of 0.1 ha across a broad latitudinal range(ca.10°).Using Hill numbers to quantify abundance-based diversity among 37,869 individuals we observed a consistent decrease in taxonomic,functional,and phylogenetic diversity as elevation increased,although the decrease was less pronounced for higher Hill orders.The exception was a slight increase in phylogenetic diversity when dominant species were over-weighted.The decrease in taxonomic and functional diversity might be attributed to an environmental filtering process towards highlands,where the increasingly harsher conditions exclude species and functional strategies.Besides,the differences in steepness decrease between Hill orders suggest that rare species disproportionately contribute to functional diversity.For phylogenetic diversity the shifting elevational trend between Hill orders indicates a greater than previously considered influence in central Andean highlands of tropical lowlands originated species with strong niche conservatism relative to distantly related temperate lineages.This could be explained by a decreasing presence and abundance of temperate,extratropical taxa towards the central Andes relative to northern or southern Andes,where they are more prevalent.

Work Ability Index and Work Ability Score: A Comparation between both Scores in a Persistent COVID-19 Cohort

Aims: The present study aims to compare the assessment of work ability based on the use of the Work Ability Index (WAI) with another questionnaire base only on the use of WAI’s first item, termed as the “Work Ability Score” (WAS). Study design: A cohort of 384 Spanish workers included in a Post COVID-19 condition or persistent COVID-19 multicenter research was utilized. Place and Duration of Study: This cohort was enlisted in four hospitals (Hospital Universitario 12 de Octubre, Madrid;Hospital Universitario Virgen Macarena, Sevilla, Andalucía;Hospital Universitario Gregorio Marañón, Madrid and Complejo Asistencial Universitario de Salamanca, Castilla y León), since 2021 until 2022. Methodology: 384 Spanish workers (176 men and 208 women;aged 20 to 70 years) with Post COVID-19 condition or persistent COVID-19 were included. Descriptive analysis of primary scores was conducted. Given the non-normal distribution of data, the Mann-Whitney and Kruskal-Wallis tests were employed. Spearman and Kendall correlations were employed to assess the relationship between WAI and WAS, also used weighted Kappa to estimate the degree agreement between WAI and WAS. Logistic regression models were utilized to study determinants influencing WAI and WAS, categorized as poor or moderate. Results: WAI had an average score of 32.98 (SD = 10.28), whereas WAS had an average of 5.95 (SD = 2.77). Significant differences were observed in both WAI and WAS across the same variables. Strong and statistically significant correlations were evident between WAI and WAS (rs = 0.83, p < 0.001). All the variables used in the logistic regression model (gender, the sector employment, and previous chronic diseases) were statistically significant in both questionnaires. Conclusion: WAS questionnaire could be used as a tool for reliable assessment of work ability among Spanish workers with Post COVID-19 condition or Persistent CO-VID-19.

Simultaneous nitrification and autotrophic denitrification in fluidized bed reactors using pyrite and elemental sulfur as electron donors

In this study, simultaneous nitrification and autotrophic denitrification (SNAD) with either elemental sulfur or pyrite were investigated in fluidized bed reactors in mesophilic conditions. The reactor performance was evaluated at different ammonium (12-40 mg/L of NH4+-N), nitrate (35-45 mg/L of NO3--N), and dissolved oxygen (DO) (0.1-1.5 mg/L) concentrations, with a hydraulic retention time of 12 h. The pyrite reactor supported the SNAD process with a maximum nitrogen removal efficiency of 139.5 mg/(L·d) when the DO concentration was in the range of 0.8-1.5 mg/L. This range, however, limited the denitrification efficiency of the reactor, which decreased from 90.0% ± 5.3% in phases II-V to 67.9% ± 7.2% in phases VI and VII. Sulfate precipitated as iron sulfate (FeSO4/Fe2(SO4)3) and sodium sulfate (Na2SO4) minerals during the experiment. The sulfur reactor did not respond well to nitrification with a low and unstable ammonium removal efficiency, while denitrification occurred with a nitrate removal efficiency of 97.8%. In the pyrite system, the nitrifying bacterium Nitrosomonas sp. was present, and its relative abundance increased from 0.1% to 1.1%, while the autotrophic denitrifying genera Terrimonas, Ferruginibacter, and Denitratimonas dominated the community. Thiobacillus, Sulfurovum, and Trichlorobacter were the most abundant genera in the sulfur reactor during the entire experiment.

Microbiota of a seepage face at the mouth of a subterranean estuary:diversity,distribution and substrate dependence

Subterranean estuaries,i.e.,the mixing zone between terrestrial groundwater and recirculated seawater,host a wide range of microbiota.Here,field campaigns were conducted at the mouth of the subterranean estuary at the Sanggou Bay(Shandong Province,China)over four consecutive seasons at a seepage face(0−20 cm depth).The diversity of benthic microbiome was characterized via 16S rRNA gene sequencing and metagenomics,combined with physic-chemical parameters,e.g.,organic carbon,total nitrogen and sulfate contents in sediments.During spring,the dominant species were assigned to the phylum Proteobacteria.Important opportunistic species was assigned to Acidobacteria,Actinobacteria and Bacteroidetes.The key components were identified to be species of the genera Pseudoalteromonas,Colwellia and Sphingobium,indicating the involvement of sediment microbiota in the degradation of sedimentary organic carbon,particularly that of pelagic origin,e.g.,phytoplankton detritus and bivalve pseudo-feces.During spring,the microbial community was statistically similar along the depth profiles and among the three sampled stations.Similar spatial distributions were obtained in the remaining seasons.By contrast,the dominant species assemblages varied significantly among seasons,with key genera being Thioprofundum and Nitrosopumilus during summer and autumn and Thioprofundum and Ilumatobacter during winter.Network analysis revealed a seasonal shift in benthic nitrogen and sulfur metabolism associated with these variations in microbial community composition.Overall,our findings suggested that macro elements derived from pelagic inputs,particularly detrital phytoplankton,shaped the microbial community compositions at the seepage face,resulting in significant seasonal variations,while the influence of terrestrial materials transported by groundwater on the sediment microbiota at the seepage face found to be minor.

Characteristics and in-hospital mortality of elderly patients with heart failure in Spanish hospitals

BACKGROUND The prevalence of heart failure(HF)increases with age,and it is one of the leading causes of hospitalization and death in older patients.However,there are little data on in-hospital mortality in patients with HF≥75 years in Spain.METHODS A retrospective analysis of the Spanish Minimum Basic Data Set was performed,including all HF episodes discharged from public hospitals in Spain between 2016 and 2019.Coding was performed using the International Classification of Diseases,10th Revision.Patients≥75 years with HF as the principal diagnosis were selected.We calculated:(1)the crude in-hospital mortality rate and its distribution according to age and sex;(2)the risk-standardized in-hospital mortality ratio;and(3)the association between in-hospital mortality and the availability of an intensive cardiac care unit(ICCU)in the hospital.RESULTS We included 354,792 HF episodes of patients over 75 years.The mean age was 85.2±5.5 years,and 59.2%of patients were women.The most frequent comorbidities were renal failure(46.1%),diabetes mellitus(35.5%),valvular disease(33.9%),cardiorespiratory failure(29.8%),and hypertension(26.9%).In-hospital mortality was 12.7%,and increased with age[odds ratio(OR)=1.07,95%CI:1.07–1.07,P<0.001]and was lower in women(OR=0.96,95%CI:0.92–0.97,P<0.001).The main predictors of mortality were the presence of cardiogenic shock(OR=19.5,95%CI:16.8–22.7,P<0.001),stroke(OR=3.5,95%CI:3.0–4.0,P<0.001)and advanced cancer(OR=2.6,95%CI:2.5–2.8,P<0.001).In hospitals with ICCU,the in-hospital risk-adjusted mortality tended to be lower(OR=0.85,95%CI:0.72–1.00,P=0.053).CONCLUSIONS In-hospital mortality in patients with HF≥75 years between 2016 and 2019 was 12.7%,higher in males and elderly patients.The main predictors of mortality were cardiogenic shock,stroke,and advanced cancer.There was a trend toward lower mortality in centers with an ICCU.

Pacman Renormalization in Siegel Parameters of Bounded Type

A novel method of renormalization called Pacman renormalization allows us to study (unicritical) Siegel functions through Pacman-type functions. It has been used to investigate the Siegel parameters with combinatorially periodic rotation number in the main cardioid of the Mandelbrot set. It is already known that it can be defined a Pacman renormalization operator such that for Siegel pacmen, with combinatorially periodic rotation numbers, the operator is compact, analytic and has a unique fixed point, at which it is hyperbolic with one-dimensional unstable manifold. In this paper we observe that this Pacman renormalization operator is compact and analytic at any Siegel Pacman or Siegel map with combinatorially bounded rotation number. This allows us to define a renormalization operator on the hybrid classes of the standard Siegel pacmen to which we built its horseshoe where the operator is topologically semiconjugated to the left shift on the space of bi-infinite sequences of natural numbers bounded by some constant.

Novel insights into D-Pinitol based therapies:a link between tau hyperphosphorylation and insulin resistance

Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.

The dorsal root ganglion as a target for neurorestoration in neuropathic pain

Neuropathic pain is a severe and chronic condition widely found in the general population.The reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in patients.During the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical stimulation.Furthermore,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative therapies.Here,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic pain.More importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.

Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

Role of lipids in the control of autophagy and primary cilium signaling in neurons

The brain is,after the adipose tissue,the organ with the greatest amount of lipids and diversity in their composition in the human body.In neurons,lipids are involved in signaling pathways controlling autophagy,a lysosome-dependent catabolic process essential for the maintenance of neuronal homeostasis and the function of the primary cilium,a cellular antenna that acts as a communication hub that transfers extracellular signals into intracellular responses required for neurogenesis and brain development.A crosstalk between primary cilia and autophagy has been established;however,its role in the control of neuronal activity and homeostasis is barely known.In this review,we briefly discuss the current knowledge regarding the role of autophagy and the primary cilium in neurons.Then we review the recent literature about specific lipid subclasses in the regulation of autophagy,in the control of primary cilium structure and its dependent cellular signaling in physiological and pathological conditions,specifically focusing on neurons,an area of research that could have major implications in neurodevelopment,energy homeostasis,and neurodegeneration.

Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resilience in Tg2576 mice.

A Shuffling-Steganography Algorithm to Protect Data of Drone Applications

In Saudi Arabia,drones are increasingly used in different sensitive domains like military,health,and agriculture to name a few.Typically,drone cameras capture aerial images of objects and convert them into crucial data,alongside collecting data from distributed sensors supplemented by location data.The interception of the data sent from the drone to the station can lead to substantial threats.To address this issue,highly confidential protection methods must be employed.This paper introduces a novel steganography approach called the Shuffling Steganography Approach(SSA).SSA encompasses five fundamental stages and three proposed algorithms,designed to enhance security through strategic encryption and data hiding techniques.Notably,this method introduces advanced resistance to brute force attacks by employing predefined patterns across a wide array of images,complicating unauthorized access.The initial stage involves encryption,dividing,and disassembling the encrypted data.A small portion of the encrypted data is concealed within the text(Algorithm 1)in the third stage.Subsequently,the parts are merged and mixed(Algorithm 2),and finally,the composed text is hidden within an image(Algorithm 3).Through meticulous investigation and comparative analysis with existing methodologies,the proposed approach demonstrates superiority across various pertinent criteria,including robustness,secret message size capacity,resistance to multiple attacks,and multilingual support.

Metastatic pancreatic and lung cancer patient in complete remission following immunotherapy: A case report and review of literature

BACKGROUND Metastatic pancreatic ductal adenocarcinoma(PDAC)is a lethal malignancy with dispiriting survival data.Immunotherapy is a promising approach to many cancer types,but achieves poor outcomes in advanced PDAC due to its immunosuppressive tumor microenvironment.We describe a case of metastatic PDAC effectively treated with pembrolizumab.CASE SUMMARY We report the case of a 67-year-old woman with unresectable locally advanced PDAC,treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus capecitabine.At nine months,pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary,confirmed by left lung biopsy.Systemic immunotherapy was then initiated with pembrolizumab,an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor types.The patient showed a complete metabolic response that was maintained throughout the treatment.The patient continues to be disease-free at 5.6 years since the start of immunotherapy.CONCLUSION These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic PDAC.To our knowledge,this is the first reported case of a patient with metastatic PDAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative surgery.Further studies are required to determine biomarkers that identify PDAC patients most likely to benefit from this immunotherapy.