Magnetic nanoflowers: a hybrid platform for enzyme immobilization.

The use of organic-inorganic hybrid nanoflowers as a support material for enzyme immobilization has gained significant attention in recent years due to their high stability, ease of preparation, and enhanced catalytic activity. However, a major challenge in utilizing these hybrid nanoflowers for enzyme immobilization is the difficulty in handling and separating them due to their low density and high dispersion. To address this issue, magnetic nanoflowers have emerged as a promising alternative enzyme immobilization platform due to their easy separation, structural stability, and ability to enhance catalytic efficiency. This review focuses on different methods for designing magnetic nanoflowers, as well as future research directions. Additionally, it provides examples of enzymes immobilized in the form of magnetic nanoflowers and their applications in environmental remediation, biosensors, and food industries. Finally, the review discusses possible ways to improve the material for enhanced catalytic activity, structural stability, and scalability.

Magnetic nanoflowers can be used as a novel platform for enzyme immobilization.There are three different approaches to the synthesis of efficient magnetic nanoflower.The magnetic nanoflowers provides excellent stability and good reusability of enzymes.The hybrid biocatalyst was applied in biotransformation, environmental, and food applications.The challenges and their remedies of hybrid biocatalyst have been discussed.

A Study of Factors Influencing Delayed Diagnosis in Pediatric Cancers: A Step Towards Better Outcomes-A Cross-sectional Study.

Annually, India contributes to one-fifth of newly diagnosed pediatric cancers worldwide. Poor outcome in India as compared with developed nations is mainly attributed to delayed diagnosis and study of factors influencing delay in diagnosis holds paramount importance in formulating strategies and counter-measures to improve survival. It was a cross-sectional study conducted on children diagnosed with malignancy at a tertiary care hospital. Diagnosis delay was defined and further divided into patient delay and physician delay. Various patient-related factors and socioeconomic factors that could affect diagnosis were studied. Statistical analysis included descriptive analysis, Mann-Whitney U test, Kruskal-Wallis test, and multivariate linear regression. Of 185 patients enrolled, median diagnosis delay, patient delay, and physician delays were 59, 30, and 7 days respectively. Median diagnosis delay was significantly higher in younger children, children of illiterate parents, and low income. Median diagnosis delay in children presenting to a general practitioner (9 [4 to 29] days) was higher than those presenting to a pediatrician (5.5 [2 to 18] days). Sex, occupation of parents, and distance from oncology center did not affect time for diagnosis. We concluded that augmentation of the parent's attitudes, increased awareness, and decentralization of specialized pediatric care to rural areas can significantly reduce mortality from, otherwise, curable malignancies.

Revisiting the Functional Impact of NK Cells.

Immune responses are critical for the maintenance of homeostasis but can also upset the equilibrium, depending on the context and magnitude of the response. Natural killer (NK) cells are well known for their important roles in antiviral and antitumor immune responses, and they are currently used, mostly under optimized forms, as immunotherapeutic agents against cancer. Nevertheless, with accumulating examples of deleterious effects of NK cells, it is paramount to consider their negative contributions. Here, we critically review and comment on the literature surrounding undesirable aspects of NK cell activity, focusing on situations where they play a harmful rather than a protective role.

Probiotic sugar confectionery fortified with flax seeds (Linum usitatissimum L.).

People have affection for confectionary products. Confectionery products are of two types, baker and sugar confectionary. Dark chocolates belong to sugar confectionery class. The present invention was carried out on the preparation of synbiotic dark chocolates. Synbiotics are food products that contain both prebiotics and probiotic microorganisms, wherein prebiotics encourage the growth of probiotics. The synbiotic dark chocolates were amended with flax seeds (Linum usitatissimum L.) as a prebiotic for LAB. Flax seed contains fiber and phenolic antioxidants which makes them prebiotic source. The isolated LAB culture, which was identified as Leuconostoc mesenteroides based on morphological, biochemical tests and MALDI-TOF, showed the properties of a probiotic culture viz., tolerance to sodium chloride, bile salt, pH, and temperature, sensitivity to antibiotics, nonhemolytic and production of hydrogen peroxide. Cytotoxic activity of the cell free supernatant was assessed against MDA MB 231 and neuroblastoma cell line. Probiotic strain showed 48% and 30% cytotoxicity against MDA MB 231 and neuroblastoma cell line. The synbiotic chocolate was found to have more antioxidant activity, i.e. 90 U/mL by DPPH assay and 200 (µg Trolox/mL) by FRAP assay. The synbiotic chocolate prepared will be beneficial for the gut health of the humans and will also have excellent nutritional value.

Genetic polymorphisms of heme-oxygenase 1 (HO-1) may impact on acute kidney injury, bronchopulmonary dysplasia, and mortality in premature infants.

BACKGROUND: Heme oxygenase 1 (HO1) catalyzes heme degradation, and offers protection for several organs, including the kidney. Genetic polymorphisms of HO-1 are associated with poor clinical outcomes in several populations. POPULATION: We prospectively enrolled 117 premature infants (birth weight ≤1,200 g or postgestational age ≤31 wk) and evaluated two DNA genetic variants proximal to the promoter region of HO-1 (GT(n) repeats, and -413T>A SNP). We evaluated how these polymorphisms affect two clinical outcomes: (i) Acute Kidney Injury (AKI)-rise in serum creatinine (SCr) ≥ 0.3 mg/dl or ≥ 150-200% from lowest previous value, (ii) the composite of mortality and bronchopulmonary dysplasia (BPD) defined as receipt of oxygen at 36 wk postmenstrual age. RESULTS: AKI occurred in 34/117 (29%) of neonates; 12/117 (10%) died; 29/105 (28%) survivors had BPD. Neonates with TT genotype at 413T>A before the HO-1 promoter had higher rates of AKI (P < 0.05). There was no difference in number of GT(n) repeats and clinical outcomes. CONCLUSION: We did not find an association between the GT(n) tandem repeat of HO-1 and AKI nor BPD/mortality. However, infants with TT genotype of the 413T>A genetic alteration had lower incidence of AKI. Further studies using larger cohorts are needed to better understand these relationships.

Risk factors for acute kidney injury during aminoglycoside therapy in patients with cystic fibrosis.

BACKGROUND: Aminoglycoside (AG) therapy is a common cause of acute kidney injury (AKI) in cystic fibrosis (CF) patients. The aim of this study was to identify factors associated with AKI during intravenous AG courses in this population. METHODS: This was a matched case-control study utilizing two independent cohorts of hospitalized CF patients receiving ≥ 3 days of intravenous AG at Cincinnati Children's Hospital Medical Center and Children's of Alabama. All admissions with AKI (cases, N = 82) were matched to two randomly selected admissions without AKI (controls, N = 164) by center, gender, and age ±3 years of the case. AKI was defined as a 1.5-fold increase in the baseline serum creatinine (SCr) level or by an increase in SCr level of 0.3 mg/dL within 48 h. Admissions with AKI before day 4 or without at least weekly SCr monitoring were excluded from the analysis. Factors were compared between cases and controls using simple and multiple conditional logistic regression. RESULTS: Multivariable analysis identified receipt of an AG within 90 days prior to admission, longer duration of AG therapy, low serum albumin, and receipt of trimethoprim/sulfamethoxazole as independent risk factors for developing AKI. Infection with Staphylococcus aureus diminished the odds of developing AKI. CONCLUSIONS: This study identifies risk factors contributing to AG-associated AKI in CF patients. These findings can be used to anticipate high-risk scenarios and limit AKI in CF patients under clinical care.

Acute kidney injury is associated with bronchopulmonary dysplasia/mortality in premature infants.

BACKGROUND: Acute kidney injury (AKI) impairs electrolyte balance, alters fluid homeostasis and decreases toxin excretion. More recent data suggest it also affects the physiology of distant organs. METHODS: We performed a prospective cohort study which invloved 122 premature infants [birth weight (BW) ≤1200 g and/or gestational age (GA) <31 weeks] to determine relationships between AKI and bronchopulmonary dysplasia (BPD)/mortality. Days until oxygen discontinuation was compared between those with and without AKI in survivors who received oxygen for ≥24 h. RESULTS: Acute kidney disease, defined by a rise in serum creatinine (SCr) of ≥0.3 mg/dl or an increase in SCr of ≥150%, occurred in 36/122 (30%) of the premature infants. Those with AKI had a 70% higher risk of oxygen requirement or of dying at 28 days of life [relative risk (RR) 1.71, 95% confidence interval (CI) 1.22-2.39; p < 0.002]. This association remained after controlling for GA, pre-eclampsia, 5 min Apgar score and percentage maximum weight change (max % weight Δ) in the first 4 days (RR 1.45, 95% CI 1.07-1.97); p < 0.02). Similar findings were noted for receipt of mechanical ventilation/death by day 28 (adjusted RR 1.53, 95% CI 1.05-2.22; p < 0.03). Those without AKI were 2.5-fold more likely to come off oxygen [hazard ratio (HR) 1.3-5; p < 0.02) than those with AKI, even when controlling for GA, pre-eclampsia, 5 min Apgar and max % weight Δ (multivariate HR 2.0, 95% CI 0.9-4.0; p < 0.06). CONCLUSIONS: In premature infants, AKI is associated with BPD/mortality. As AKI could lead to altered lung physiology, interventions to ameliorate AKI could improve long-term BPD.

ALL induction outcome: Real-world data from a pediatric oncology center in an LMIC setup with rural predominance.

BACKGROUND: Acute lymphoblastic leukemia (ALL) has survival rates of greater than 90% in developed nations. However, various sociodemographic factors adversely affect outcome rates in low- and middle-income countries (LMICs). OBJECTIVE: To study induction outcome of ALL and various factors affecting it. METHODS: This was a prospective cohort study which enrolled 86 children up to the age of 18 years with newly diagnosed ALL registered in newly established pediatric hematology and oncology division over the duration of 3 years. Sociodemographic and clinical data was collected. Outcome was assessed using morphological remission, minimal residual disease (MRD) and mortality rate. RESULTS: Of the 170 children with malignancies registered, 86 were ALL. Mean age was 7.09 ± 4.07 years and the M: F ratio of 1.32:1. Sixteen (38.09%) of them had severe acute malnutrition and another 16 (38.09%) had moderate acute malnutrition. Thirty (68.18%) children over 5 years were undernourished. Seventy-four (86.05%) were B-ALL and 12 (13.95%) T-ALL. In total, 28.77% had WBC counts greater than 50 × 10 9 /L. t (12;21) was the most common cytogenetic abnormality. Majority (60.46%) of the patients belonged to lower socioeconomic status. Seventy-one (93.42%) patients completed induction of which 100% attained morphological remission and 64 (90.14%) were MRD negative. There were five mortalities, three (60%) due to sepsis and 2 (40%) due to hemophagocytic lymphohistiocytosis. Fifty (65.78%) children had morbidities during induction, febrile neutropenia being the commonest. CONCLUSIONS: Successful induction outcome rates at par with high-income countries can be achieved even in resource-limited settings of LMIC with support from government and NGOs. Decentralized cancer care centers can effectively pave the way in reducing cancer mortality in children of lower socioeconomic status residing in rural areas.

Flaxseed Mucilage/Hydroxypropyl Methylcellulose and Sodium Alginate/Polyvinyl Alcohol Composite Bilayer Film as a Promising Drug Carrier for Periodontal Treatment.

Objectives: The present study focused on the formulation of mucoadhesive bilayer composite films for the treatment of periodontitis and evaluation of their physicochemical properties. Materials and Methods: The solvent casting technique was used to prepare films. The primary layer (D) was prepared with flaxseed and hydroxypropyl methylcellulose composite to sustain the release of doxycycline hyclate. The second layer (S) comprised sodium alginate and polyvinyl alcohol composite for faster release of clove oil. Both layers were combined to generate the bilayer film (B). All formulations were characterized further to obtain an optimized formulation. Results: Attenuated total reflection-Fourier transform infrared radiation results showed intactness of drug and clove oil in the presence of excipients. The pH of the films was compatible with the periodontal cavity and the thickness was suitable for inserting into the cavity. The immediate release layer showed faster disintegration and swelling. The content of clove oil was above 80%. The rate of swelling of the primary layer was slow and drug content complied with the United States Pharmacopoeia. Scanning electron microscope analysis revealed intact, non-porous and smooth films. Films exhibited better mechanical strength and bioadhesiveness. Clove oil was released from the immediate release layer within 10 min, and doxycycline hyclate release was retarded to a minimum of up to 8 h in the primary layer as well as the bilayer. Formulation also had a significant effect on both Escherichia coli and Staphylococcus aureus. Conclusion: In the current study, bilayers were successfully prepared and characterized. The optimized formulation can be effectively used for the treatment of periodontitis.

Novel dual cyclooxygenase and lipoxygenase inhibitors targeting hyaluronan-CD44v6 pathway and inducing cytotoxicity in colon cancer cells.

Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzyme have been found to play a role in promoting growth in colon cancer cell lines. The di-tert-butyl phenol class of compounds has been found to inhibit both COX-2 and 5-LOX enzymes with proven effectiveness in arresting tumor growth. In the present study, the structural analogs of 2,6 di-tert-butyl-p-benzoquinone (BQ) appended with hydrazide side chain were found to inhibit COX-2 and 5-LOX enzymes at micromolar concentrations. Molecular docking of the compounds into COX-2 and 5-LOX protein cavities indicated strong binding interactions supporting the observed cytototoxicities. The signaling interaction between endogenous hyaluronan and CD44 has been shown to regulate COX-2 activities through ErbB2 receptor tyrosine kinase (RTK) activation. In the present studies it has been observed for the first time, that three of our COX/5-LOX dual inhibitors inhibit proliferation upon hydrazide substitution and prevent the activity of pro-angiogenic factors in HCA-7, HT-29, Apc10.1 cells as well as the hyaluronan synthase-2 (Has2) enzyme over-expressed in colon cancer cells, through inhibition of the hyaluronan/CD44v6 cell survival pathway. Since there is a substantial enhancement in the antiproliferative activities of these compounds upon hydrazide substitution, the present work opens up new opportunities for evolving novel active compounds of BQ series for inhibiting colon cancer.

Fluid overload and mortality are associated with acute kidney injury in sick near-term/term neonate.

BACKGROUND: Acute kidney injury (AKI) is common and portends mortality in several neonatal cohorts. Fluid overload is independently associated with poor outcomes in children and adults but has not been extensively studied in neonates. METHODS: Between February 2010 and May 2011, we followed 58 neonates who met the following criteria: birth weight >2,000 g, gestational age ≥ 34 weeks, 5-min Apgar ≤ 7, and parental consent. Serum creatinine (SCr) was measured daily for first 4 days of life. AKI was defined as a rise in SCr of > 0.3 mg/dl or persistent SCr above 1.5 mg/dl. RESULTS: AKI was present in 9/58 (15.6 %) neonates and was associated with higher birth weight, being male, lower 5-min Apgar scores, lower cord pH, delivery room intubation, and absence of maternal pre-eclampsia. Percent weight accumulation at day 3 of life was higher in those with AKI [median=8.2, interquartile range (IQR) =4.4-21.6)] than without AKI (median= -4 (IQR= -6.5 to 0.0) (p<0.001). Infants with AKI had lower survival rates than those without AKI [7/9 (72 %) vs. 49/49 (100 %) (p<0.02)]. CONCLUSIONS: AKI incidence in this neonatal population is similar to other neonatal cohorts. Near-term/term infants with AKI have a higher mortality rate and a net positive fluid balance over the first few days of life.

Characterisation of the pro-inflammatory cytokine signature in severe COVID-19.

Clinical outcomes from infection with SARS-CoV-2, the cause of the COVID-19 pandemic, are remarkably variable ranging from asymptomatic infection to severe pneumonia and death. One of the key drivers of this variability is differing trajectories in the immune response to SARS-CoV-2 infection. Many studies have noted markedly elevated cytokine levels in severe COVID-19, although results vary by cohort, cytokine studied and sensitivity of assay used. We assessed the immune response in acute COVID-19 by measuring 20 inflammatory markers in 118 unvaccinated patients with acute COVID-19 (median age: 70, IQR: 58-79 years; 48.3% female) recruited during the first year of the pandemic and 44 SARS-CoV-2 naïve healthy controls. Acute COVID-19 was associated with marked elevations in nearly all pro-inflammatory markers, whilst eleven markers (namely IL-1ß, IL-2, IL-6, IL-10, IL-18, IL-23, IL-33, TNF-α, IP-10, G-CSF and YKL-40) were associated with disease severity. We observed significant correlations between nearly all markers elevated in those infected with SARS-CoV-2 consistent with widespread immune dysregulation. Principal component analysis highlighted a pro-inflammatory cytokine signature (with strongest contributions from IL-1ß, IL-2, IL-6, IL-10, IL-33, G-CSF, TNF-α and IP-10) which was independently associated with severe COVID-19 (aOR: 1.40, 1.11-1.76, p=0.005), invasive mechanical ventilation (aOR: 1.61, 1.19-2.20, p=0.001) and mortality (aOR 1.57, 1.06-2.32, p = 0.02). Our findings demonstrate elevated cytokines and widespread immune dysregulation in severe COVID-19, adding further evidence for the role of a pro-inflammatory cytokine signature in severe and critical COVID-19.

Cold Agglutinin Disease and Autoimmune Hemolytic Anemia with Pulmonary Embolism as a Presentation of COVID-19 Infection.

BACKGROUND: Lymphopenia, thrombocytopenia, and elevated D-dimer and ferritin levels are frequently reported in patients with severe coronavirus disease 2019 (COVID-19). Here we report a case of cold agglutinin disease (CAD), autoimmune hemolytic anemia (AIHA), and pulmonary embolism as a presentation of COVID-19 infection. CASE REPORT: A 51-year-old African-American woman presented to the emergency room with fever and shortness of breath. She was tachycardic, febrile, and had an oxygen saturation of 88% on room air. Laboratory studies showed hemoglobin (Hb) 5.1 g/dL, D-dimer 4.55 µg/mL, and C-reactive protein 12.3 mg/dL. Computed tomography scan of the chest showed acute pulmonary embolism involving the bilateral lower lobe segmental branches. Her influenza test was negative, but her SARS-CoV-2 test returned positive. Due to severe anemia, she was not started on any anticoagulation. Haptoglobin was low. Direct antiglobulin test returned positive for anticomplement and negative for anti-immunoglobulin G. Cold agglutinin titer was 80. Mycoplasma, Epstein-Barr virus, parvovirus, human immunodeficiency viruses, and acute hepatitis screen were negative. Abdominal and pelvic computed tomography showed a normal liver and spleen without lymphadenopathy. Peripheral blood smear showed red blood cell agglutination. On Day 2, she became hypoxic requiring 6 L oxygen. Since her Hb remained stable, she was started on low-intensity unfractionated heparin. Inflammatory markers subsequently improved and she was weaned off oxygen. Her Hb remained stable at 9 g/dL and she was discharged home. After 2 weeks, her Hb increased to 11 g/dL. CONCLUSION: As exemplified in this case report, COVID-19 infection can lead to thromboembolism, CAD, and AIHA and it should be recognized as a potential etiology to such rare diseases.

Imprint of Initial Education and Loss of Ly49C/I in Activated Natural Killer Cells of TAP1-KO and C57BL/6 Wildtype Mice.

Natural killer (NK) cells are important effectors of the innate immune system and participate in the first line of defense against infections and tumors. Prior to being functional, these lymphocytes must be educated or licensed through interactions of their major histocompatibility complex class I molecules with self-specific inhibitory receptors that recognize them. In the absence of such contacts, caused by either the lack of expression of the inhibitory receptors or a very low level of major histocompatibility complex class I (MHC class I) proteins, NK cells are hypo-reactive at baseline (ex vivo). After stimulation (assessed through plate-bound antibodies against activating receptors or culture in the presence of cytokines such as interleukin (IL)-2 or IL-15) however, they can become cytotoxic and produce cytokines. This is particularly the case in transporter associated with antigen processing (TAP)-deficient mice, which we investigated in the present study. Transporter associated with antigen processing transports endogenous peptides from the cytosol to the endoplasmic reticulum, where they are loaded on nascent MHC class I molecules, which then become stable and expressed at the cell surface. Consequently, TAP-KO mice have very low levels of MHC class I expression. We present a study about phenotypic and functional aspects of NK cells in two mouse strains, C57BL/6 wildtype and TAP1-KO in spleen and lung. We observed that in both types of mice, on the same genetic background, the initial pattern of education, conferred to the cells via the inhibitory receptors Ly49C/I and NKG2A, was maintained even after a strong stimulation by the cytokines interleukin-2, interleukin-12, interleukin-15 and interleukin-18. Furthermore, the percentages of activated NK cells expressing Ly49C/I and Ly49I were strongly down-modulated under these conditions. We completed our investigations with phenotypic studies of NK cells from these mice.

Unbiased Screening Identifies Functional Differences in NK Cells After Early Life Psychosocial Stress.

Early Life Adversity (ELA) is closely associated with the risk for developing diseases later in life, such as autoimmune diseases, type-2 diabetes and cardiovascular diseases. In humans, early parental separation, physical and sexual abuse or low social-economic status during childhood are known to have great impact on brain development, in the hormonal system and immune responses. Maternal deprivation (MD) is the closest animal model available to the human situation. This paradigm induces long lasting behavioral effects, causes changes in the HPA axis and affects the immune system. However, the mechanisms underlying changes in the immune response after ELA are still not fully understood. In this study we investigated how ELA changes the immune system, through an unbiased analysis, viSNE, and addressed specially the NK immune cell population and its functionality. We have demonstrated that maternal separation, in both humans and rats, significantly affects the sensitivity of the immune system in adulthood. Particularly, NK cells' profile and response to target cell lines are significantly changed after ELA. These immune cells in rats are not only less cytotoxic towards YAC-1 cells, but also show a clear increase in the expression of maturation markers after 3h of maternal separation. Similarly, individuals who suffered from ELA display significant changes in the cytotoxic profile of NK cells together with decreased degranulation capacity. These results suggest that one of the key mechanisms by which the immune system becomes impaired after ELA might be due to a shift on the senescent state of the cells, specifically NK cells. Elucidation of such a mechanism highlights the importance of ELA prevention and how NK targeted immunotherapy might help attenuating ELA consequences.

The untapped potential of magnetic nanoparticles for forensic investigations: A comprehensive review.

With a growing interest in precise and sensitive diagnosis for criminal investigations, nanoparticles (NPs) have intrigued scientific minds working in the field of forensic science due to their exceptional properties. Magnetic nanoparticles (MNPs) have emerged as a powerful tool for improving forensic analysis due to their super magnetic behavior combined with smaller dimensions. MNP-based applications can benefit criminologists to solve criminal mysteries with greater precision and pace. This review highlights the different types of MNP-based applications and their developmental and implicational aspects of forensic science. It also renders insight into the future prospects of a splendid blend of nanotechnology and forensic science, leading to a better scientific analysis.

Airway Natural Killer Cells and Bacteria in Health and Disease.

Natural killer (NK) cells are innate lymphoid cells at the interface between innate and adaptive immunity and mostly studied for their important roles in viral infections and malignant tumors. They can kill diseased cells and produce cytokines and chemokines, thereby shaping the adaptive immune response. Nowadays, NK cells are considered as a strong weapon for cancer immunotherapy and can for example be transduced to express tumor-specific chimeric antigen receptors or harnessed with therapeutic antibodies such as the so-called NK engagers. Whereas a large body of literature exists about the antiviral and antitumoral properties of NK cells, their potential role in bacterial infections is not that well delineated. Furthermore, NK cells are much more heterogeneous than previously thought and have tissue-characteristic features and phenotypes. This review gives an overview of airway NK cells and their position within the immunological army dressed against bacterial infections in the upper and predominantly the lower respiratory tracts. Whereas it appears that in several infections, NK cells play a non-redundant and protective role, they can likewise act as rather detrimental. The use of mouse models and the difficulty of access to human airway tissues for ethical reasons might partly explain the divergent results. However, new methods are appearing that are likely to reduce the heterogeneity between studies and to give a more coherent picture in this field.

Exceptional Response to A Single Cycle of Immunotherapy in a Lynch Syndrome Patient with Metastatic Pancreatic Adenocarcinoma.

BACKGROUND Pancreatic adenocarcinoma (PDA) is associated with an 8.6-fold increased risk in Lynch syndrome patients. Here, we report the case of a Lynch syndrome PDA patient with an exceptional response to a single cycle of pembrolizumab immunotherapy. CASE REPORT A 65-year-old male patient with Lynch syndrome mismatch repair (MMR) deficient PDA with metastatic liver disease, received 1 cycle of pembrolizumab (200 mg) after progressing on 2 standard lines of treatment. His initial computed tomography (CT) showed 3×2.5 cm PDA. At that time, the disease was considered borderline resectable, and the patient received 6 cycles of FOLFIRINOX followed by chemoradiotherapy with capecitabine. A follow-up CT scan showed multiple new liver lesions. The biopsy showed metastatic PDA and tumor tissue demonstrated high microsatellite instability with abnormal/lost expression of MLH1 and PMS2 proteins. The patient was started on pembrolizumab. Only 1 cycle was given due to the development of thromboembolic complications: pulmonary embolism and myocardial infarction. His thrombophilia workup was negative. Restaging CT scans at 3, 6, and 9 months after 1 cycle of pembrolizumab revealed an excellent response with shrinkage of liver lesions. Restaging at 11 months showed the eventual resolution of most liver lesions. No new metastatic disease developed. A repeat biopsy of the dominant liver lesion showed no morphological evidence of PDA. CONCLUSIONS Only 1 cycle of pembrolizumab resulted in clinical complete response and pathologic response in metastatic PDA. We emphasize the importance of testing for MMR status and treating with immunotherapy in metastatic PDA patients with MMR deficiency.