Concomitant heparin use promotes skin graft donor site healing by basic fibroblast growth factor: A pilot prospective randomized controlled study.

Owing to its mitogenic and angiogenic characteristics, the use of basic fibroblast growth factor (bFGF) to promote wound healing has been investigated. However, its clinical efficacy has fallen short of expectations due to its instability. Heparin has been reported to stabilize bFGF. Therefore, we hypothesized that the combination of these agents would more effectively promote wound healing than bFGF alone; a single-center, two-arm parallel, single-blind, and a prospective randomized controlled pilot study was therefore performed involving 12 patients who underwent split-thickness skin graft harvesting. To ensure a feasible clinical treatment model, commercially available agents were used. The patients were randomly assigned to either the control group treated with bFGF (n = 6) or the intervention group treated with bFGF and heparin (n = 6) in a 1:1 ratio. The wound area and the wound area variation was assessed each week postoperatively, as was the number of days required for epithelialization. As a supplementary analysis, the least-squares means were calculated using a linear mixed-effects model. The results of this study indicate that the combination of bFGF and heparin may more effectively promote wound healing than bFGF alone, consistent with our hypothesis. A multicenter trial based on these data is ongoing.

Transformation into acute myeloid leukemia with t(8;21)(q22;q22.1); RUNX1::RUNX1T1 from JAK2-mutated essential thrombocythemia: a case report.

BACKGROUND: Blast transformation is a rare but well-recognized event in Philadelphia-negative myeloproliferative neoplasms associated with a poor prognosis. Secondary acute myeloid leukemias evolving from myeloproliferative neoplasms are characterized by a unique set of cytogenetic and molecular features distinct from de novo disease. t(8;21) (q22;q22.1); RUNX1::RUNX1T1, one of the most frequent cytogenetic abnormalities in de novo acute myeloid leukemia, is rarely observed in post-myeloproliferative neoplasm acute myeloid leukemia. Here we report a case of secondary acute myeloid leukemia with t(8;21) evolving from JAK2-mutated essential thrombocythemia. CASE PRESENTATION: The patient was a 74-year-old Japanese woman who was referred because of thrombocytosis (platelets 1046 × 109/L). Bone marrow was hypercellular with increase of megakaryocytes. Chromosomal analysis presented normal karyotype and genetic test revealed JAK2 V617F mutation. She was diagnosed with essential thrombocythemia. Thrombocytosis had been well controlled by oral administration of hydroxyurea; 2 years after the initial diagnosis with ET, she presented with leukocytosis (white blood cells 14.0 × 109/L with 82% of blasts), anemia (hemoglobin 91 g/L), and thrombocytopenia (platelets 24 × 109/L). Bone marrow was hypercellular and filled with 80% of myeloperoxidase-positive blasts bearing Auer rods. Chromosomal analysis revealed t(8;21) (q22;q22.1) and flow cytometry presented positivity of CD 13, 19, 34, and 56. Molecular analysis showed the coexistence of RUNX1::RUNX1T1 chimeric transcript and heterozygous JAK2 V617F mutation in leukemic blasts. She was diagnosed with secondary acute myeloid leukemia with t(8;21)(q22;q22.1); RUNX1::RUNX1T1 evolving from essential thrombocythemia. She was treated with combination chemotherapy with venetoclax and azacytidine. After the first cycle of the therapy, blasts disappeared from peripheral blood and decreased to 1.4% in bone marrow. After the chemotherapy, RUNX1::RUNX1T1 chimeric transcript disappeared, whereas mutation of JAK2 V617F was still present in peripheral leukocytes. CONCLUSIONS: To our best knowledge, the present case is the first one with JAK2 mutation preceding the acquisition of t(8;21). Our result suggests that t(8;21); RUNX1::RUNX1T1 can be generated as a late event in the progression of JAK2-mutated myeloproliferative neoplasms. The case presented typical morphological and immunophenotypic features associated with t(8;21) acute myeloid leukemia.

Adverse events of COVID-19 vaccination during 2021-2022 suppressed by breakfast consumption and favorable sleeping habit among Japanese university students.

Introduction: Young adults are hesitant to receive the coronavirus disease 2019 (COVID-19) vaccination owing to concerns regarding adverse events despite the effectiveness of vaccines in preventing SARS-CoV-2 infection-associated serious illness, hospitalization, and death. Methods: A retrospective cohort study was conducted in Gifu University students receiving the mRNA-1273 vaccine and boosters to elucidate the real incidence of adverse events and factors that prevent them. We examined the adverse events and identified potential risk factors through a self-administered questionnaire on the participants' physical condition after COVID-19 vaccination. Results: Focal/systemic adverse events were highly frequent among university students after receiving the COVID-19 vaccine; however, there were no life-threatening cases or hospitalizations over two years. A higher number of vaccinations (p < 0.001), female sex (p < 0.001), and lower body mass index (BMI) (p = 0.002) were associated with an increased incidence of adverse events on the day of COVID-19 vaccination or the day after vaccination. Regular breakfast consumption was significantly associated with a decreased incidence of post-vaccination itching (p = 0.019) and abdominal pain and diarrhea (p = 0.042). Sufficient sleep duration was significantly associated with a decreased incidence of post-vaccination abdominal pain and diarrhea (p = 0.042). Conclusions: High frequency of adverse events of COVID-19 mRNA-1273 among Japanese university students was reported. A higher number of shots, female sex, and lower BMI were associated with a higher incidence of adverse events. Regular breakfast and sufficient sleep were associated with fewer adverse events. This study may provide a possible solution to the worldwide problem of vaccine hesitancy.

Crosstalk between kidney and bone: insights from CKD-MBD.

The kidneys play an important role in the regulation of phosphate and calcium balance and serum concentrations, coordinated by fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D (1,25D). In patients with chronic kidney disease (CKD), this regulation is impaired, leading to CKD-mineral and bone disorder (CKD-MBD), characterized by decreased 1,25D, elevated FGF23, secondary hyperparathyroidism, hyperphosphatemia, bone abnormalities, and vascular and soft-tissue calcification. While bone abnormalities associated with CKD-MBD, known as renal osteodystrophy, have been recognized as the most typical interaction between the kidney and bone, a number of other kidney-bone interactions have been identified, for which our knowledge of the pathogenesis of CKD-MBD has played an important role. This article summarizes recent findings on CKD-MBD and explores the crosstalk between the kidney and bone from the perspective of CKD-MBD.

Skin Perfusion Pressure Outperforms Ankle-Brachial Index in Predicting Mortality and Cardiovascular Outcomes in Hemodialysis Patients.

AIMS: Skin perfusion pressure (SPP) and ankle-brachial index (ABI) are useful in screening for peripheral arterial disease in patients undergoing hemodialysis (HD). We compared the prognostic abilities of the SPP and ABI in predicting the composite outcomes of mortality and atherosclerotic vascular events. METHODS: This single-center prospective cohort study enrolled 258 patients undergoing HD. The patients with SPP and ABI measurements were divided into tertiles. Log-rank tests, Cox regression analyses, and discrimination parameters were used for comparisons. RESULTS: Over a median follow-up period of 3.7 (1.4-5.0) years, 119 composite events were recorded. The incidence rates of composite events were 27.5, 13.3, and 9.1 per 100 person years, respectively, across the SPP tertiles (log-rank: p＜0.001), and 23.2, 13.2, and 11.6 per 100 person years across the ABI tertiles (p=0.003). With the 3rd tertiles as references, the 1st tertiles of the SPP and ABI were significantly associated with the composite outcome (adjusted hazard ratio [aHR]: 2.58, 95% confidence interval [CI]: 1.57-4.23 and aHR: 1.70, 95% CI: 1.06-2.73, respectively). Adding the tertiles of the SPP to a predictive model with established risk factors significantly improved the model performance. This improvement was larger than that of the ABI in terms of net reclassification (0.330 vs. 0.275) and integrated discrimination (0.045 vs. 0.012). Furthermore, in patients with a normal ABI, the 1st SPP tertile (＜71 mmHg) was significantly associated with the outcome (aHR, 1.97; 95% CI, 1.13-3.41) when compared to the 3rd tertile. CONCLUSIONS: Even patients with a normal ABI have a poor prognosis if their SPP levels are low. SPP outperformed ABI in predicting mortality and cardiovascular outcomes in HD patients.

Nephrology referral slows the progression of chronic kidney disease, especially among patients with anaemia, diabetes mellitus, or hypoalbuminemia: A single-centre, retrospective cohort study.

BACKGROUND: The Kidney Disease Improving Global Outcomes guidelines recommend nephrology referral for patients with chronic kidney disease (CKD) stages 4 to 5, significant proteinuria and persistent microscopic haematuria. However, the recommendations are opinion-based and which patients with CKD benefit more from nephrology referral has not been elucidated. METHODS: In this retrospective cohort study, patients referred to our nephrology outpatient clinic from April 2017 to March 2019 were included. We excluded patients considered to have an acute decline in kidney function (annual decline in estimated glomerular filtration rate [eGFR] >10 mL/min/1.73 m2). The slopes of eGFR before and after nephrology referral were estimated and compared by linear mixed effects models. Interaction between time and referral status (before or after referral) was assessed and effect modifications by the presence of diabetes, proteinuria (defined by urine dipstick protein 2+ or more), urine occult blood, hypoalbuminemia (defined by albumin levels less than 3.5 g/dL) and anaemia (defined by haemoglobin levels less than 11.0 g/dL) were evaluated. RESULTS: The eGFR slope significantly improved from -2.05 (-2.39 to -1.72) to -0.96 (-1.36 to -0.56) mL/min/1.73 m2/year after nephrology referral (p < .001). The improvement in eGFR slope was more prominent among those with diabetes mellitus, anaemia, and hypoalbuminemia (all p-values for three-way interaction <.001 after adjustment for covariates). Further adjustments for time-dependent haemoglobin levels, the use of erythropoiesis-stimulating agents, iron supplementation, anti-hypertensives and anti-diabetic medications did not change the significance of the interactions. CONCLUSIONS: Nephrology referral slows CKD progression, especially among those with hypoalbuminemia, diabetes or anaemia. Patients with hypoalbuminemia, diabetes or anaemia might benefit more from specialized care and lifestyle modifications by nephrologists. The inclusion of anaemia and hypoalbuminemia in nephrology referral criteria should be considered.

Nafamostat mesylate decreases skin flap necrosis in a mouse model of type 2 diabetes by protecting the endothelial glycocalyx.

The success rate of flap tissue reconstruction has increased in recent years owing to advancements in microsurgical techniques. However, complications, such as necrosis, are still more prevalent in diabetic patients compared to non-diabetic individuals, presenting an ongoing challenge. To address this issue, many previous studies have examined vascular anastomoses dilation and stability, primarily concerning surgical techniques or drugs. In contrast, in the present study, we focused on microvascular damage of the peripheral microvessels in patients with diabetes mellitus and the preventative impact of nafamostat mesylate. Herein, we aimed to investigate the effects of hyperglycemia on glycocalyx (GCX) levels in mice with type 2 diabetes. We examined the endothelial GCX (eGCX) in skin flap tissue of 9-12-week-old type 2 diabetic mice (db/db mice) using a perforator skin flap and explored treatment with nafamostat mesylate. The growth rates were compared after 1 week. Heterotype (db/+) mice were used as the control group. Morphological examination of postoperative tissues was performed at 1, 3, 5, and 7 days post-surgery. In addition, db/db mice were treated with 30 mg/kg/day of nafamostat mesylate daily and were evaluated on postoperative day 7. Seven days after surgery, all db/db mice showed significant partial flap necrosis. Temporal observation of the skin flaps revealed a stasis-like discoloration and necrosis starting from the contralateral side of the remaining perforating branch. The control group did not exhibit flap necrosis, and the flap remained intact. In the quantitative assessment of endothelial glycans using lectins, intensity scoring showed that the eGCX in the db/db group was significantly thinner than that in the db/+ group. These results were consistent with the scanning electron microscopy findings. In contrast, treatment with nafamostat mesylate significantly improved the flap engraftment rate and suppressed eGCX injury. In conclusion, treatment with nafamostat mesylate improves the disrupted eGCX structure of skin flap tissue in db/db mice, potentially ameliorating the impaired capillary-to-venous return in the skin flap tissue.

Right subclavian artery injury during catheter insertion into the right internal jugular vein treated with endovascular stent graft placement after balloon occlusion test: A case report.

Subclavian artery injuries during internal jugular vein puncture when attempting central venous catheter insertion are rare. A 60-year-old man undergoing treatment for neuromyelitis optica with paralysis and sensory loss developed a complication during catheter placement into his right internal jugular vein for plasmapheresis. His previous physician felt resistance and discontinued the procedure. The patient later developed mild dyspnea and dysphagia. Computed tomography scans indicated thrombus formation and tracheal deviation. Contrast-enhanced computed tomography scans showed right subclavian artery injury with extravasation and a large pseudoaneurysm. Following transferal to our hospital, he was stable and asymptomatic; however, contrast-enhanced computed tomography scans showed a pseudoaneurysm located proximal to the right subclavian artery. Considering challenges with compression hemostasis and the invasiveness of open surgery, endovascular treatment was selected using a VIABAHN stent graft. A balloon occlusion test of the right vertebral artery was performed to assess stroke risk. Prophylactic embolization of the right vertebral artery, internal thoracic artery, and thyrocervical trunk were performed to prevent a type 2 endoleak. On hospital day 5, our patient showed no postoperative complications and was transferred to the referring hospital. Follow-up imaging showed the graft was intact with no pseudoaneurysm, confirming successful treatment. Endovascular treatment with a stent graft is highly effective for peripheral artery injuries. Using a balloon occlusion test to assess collateral blood flow and stroke risk is essential pretreatment, especially when a graft might occlude the vertebral artery. Balloon occlusion tests are recommended when planning treatment for iatrogenic and other types of subclavian artery injuries.

Urinary liver-type fatty acid-binding protein levels may be associated with the occurrence of acute kidney injury induced by trauma.

Introduction: Acute kidney injury (AKI), with a fatality rate of 8.6%, is one of the most common types of multiorgan failure in the intensive care unit (ICU). Thus, AKI should be diagnosed early, and early interventions should be implemented. Urinary liver-type fatty acid-binding protein (L-FABP) could aid in the diagnosis of AKI. Methods: In this prospective, single-center, observational study, we included 100 patients with trauma. Urinary L-FABP levels were measured using a semi-quantitative rapid assay kit 6 and 12 h after injury. Negative, weakly positive, and strongly positive urinary L-FABP levels were examined using two protocols. Using protocol 1, measurements were performed at 6 h after injury negative levels were considered "negative," and weakly positive and strongly positive levels were considered "positive." Using protocol 2, strongly positive levels at 6 h after injury were considered "positive," and negative or weakly positive levels at 6 h after injury were considered "positive" if they were weakly positive or positive at 12 h after injury. Results: Fifteen patients were diagnosed with AKI. Using protocol 1, the odds ratio (OR) was 20.55 (p = 0.001) after adjustment for the injury severity score (ISS), contrast media use, and shock index. When the L-FABP levels at 6 and 12 h were similarly adjusted for those three factors, the OR was 18.24 (p < 0.001). The difference in ORs for protocols 1 and 2 was 1.619 (p = 0.04). Discussion: Associations between urinary L-FABP and AKI can be examined more precisely by performing measurements at 6 and 12 h after injury than only one time at 6 h.

Adjunct Acupuncture Improved Respiratory Status and Weaning from Mechanical Ventilation After Severe COVID-19 Pneumonia.

Background: A patient with severe COVID-19 pneumonia had adjunctive acupuncture to improve respiration and facilitate weaning off prolonged mechanical ventilation (MV). Case: A man in his 40s with COVID-19 was in an advanced critical-care center on symptom day 5 for respiratory failure due to pneumonia requiring MV therapy. He received high-dose corticosteroid pulse therapy, antiviral agents, and multiple antibiotics for complicated bacterial pneumonia and bacteremia. Repeated MV weaning attempts failed, although his pneumonia gradually improved. Then, acupuncture 4 times per week was started to improve his respiration and facilitate MV weaning from day 49 of his symptoms' onset. Results: His weaning-related indices improved, including reductions in respiratory rate and Rapid Shallow Breath Index. His O2 saturation increased immediately after each acupuncture treatment. The day after the first acupuncture treatment, his MV support was reduced by changing ventilation mode from synchronized intermittent mandatory ventilation mode to continuous positive airway pressure (CPAP) mode during the day without exacerbation of respiratory status. After 3 days of acupuncture, this patient was on CPAP support alone. MV therapy was discontinued completely after 8 days of acupuncture (6th acupuncture treatment). Conclusions: Acupuncture improved respiration and facilitated MV weaning in a patient with respiratory failure secondary to COVID-19. Adjunctive acupuncture may benefit such patients and others after severe pneumonia. Large cohort studies are needed.

Recombinant antithrombin attenuates acute kidney injury associated with rhabdomyolysis: an in vivo animal study.

BACKGROUND: Rhabdomyolysis is characterized by the destruction and necrosis of skeletal muscle tissue, resulting in acute kidney injury (AKI). Recombinant antithrombin (rAT) has DNA repair and vascular endothelial-protection properties. Herein, we investigated whether rAT therapy has beneficial effects against rhabdomyolysis-induced AKI. Ten-week-old male B6 mice were injected with 5 mL/kg of 50% glycerol intramuscularly in the left thigh after 24 h of fasting to create a rhabdomyolysis mouse model. Further, 750 IU/kg rAT was injected intraperitoneally at 24 and 72 h after the rhabdomyolysis model was established. The mice were euthanized after 96 h for histological analysis. Saline was administered to mice in the control group. RESULTS: Blood tests show elevated serum creatinine, urea nitrogen, and neutrophil gelatinase-associated lipocalin levels in rhabdomyolysis. Loss of tubular epithelial cell nuclei and destruction of the tubular luminal surface structure was observed in the untreated group, which improved with rAT treatment. Immunostaining for Ki-67 showed increased Ki-67-positive nuclei in the tubular epithelial cells in the rAT group, suggesting that rAT may promote tubular epithelial cell regeneration. The microvilli of the brush border of the renal tubules were shed during rhabdomyolysis, and rAT treatment reduced this injury. The vascular endothelial glycocalyx, which is usually impaired by rhabdomyolysis, became functional following rAT treatment. CONCLUSIONS: Treatment with rAT suppressed rhabdomyolysis-induced AKI, suggesting that rAT therapy may be a novel therapeutic approach.

Impact of augmented renal clearance on anticoagulant therapy in critically ill patients with coronavirus disease 2019: A retrospective cohort study.

INTRODUCTION: This study aimed to determine the impact of augmented renal clearance (ARC) on anticoagulation therapy in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: This retrospective cohort study included adult patients with severe COVID-19 with ARC who had been treated at our hospital between 2020 and 2021. We measured the estimated glomerular filtration rate calculated by the Chronic Kidney Disease Epidemiology Collaboration formula (eGFRCKD-EPI) every morning, and ARC condition was defined as eGFRCKD-EPI ≥ 130 mL/min/1.73 m2. Multivariate regression analysis with Huber-White sandwich estimator was performed to examine the association of unfractionated heparin (UH) dosage between blood test timings with activated partial thromboplastin time (APTT) compared with and without ARC. RESULTS: We identified 38 enrolled patients: seven and 31 in the ARC and non-ARC groups, respectively. In the ARC coexisting condition, a higher dose of UH, which corresponded to the total dose in 24 h from the previous day, was required to achieve the same APTT prolongation, with a significant difference (p < 0.001). CONCLUSIONS: Our study suggests that careful monitoring and consideration of higher UH doses in critically ill patients with COVID-19 is necessary because anticoagulation failure can occur during ARC.

[Case of Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm of the Papilla of Vater Metastasizing to the Lung after Resection].

A 79-year-old man visited a hospital for right upper abdominal pain and nausea. After conservative treatment for cholangitis and pancreatitis owing to a pancreatic head lesion, he was referred to our hospital for further evaluation and treatment of the lesion. He was diagnosed with pancreatic head cancer or carcinoma of papilla of Vater and underwent subtotal stomach- preserving pancreaticoduodenectomy. Postoperative histopathological examination revealed the coexistence of adenocarcinoma( 60%)and neuroendocrine carcinoma(40%)components, consistent with the diagnosis of mixed neuroendocrine- non-neuroendocrine neoplasm(MiNEN). In addition, regional lymph node metastasis of the adenocarcinoma component was found. Adjuvant chemotherapy was not administered because of a poor performance status. Lung metastasis occurred 13 months after surgery. Chemotherapy with S-1 was administered, and partial response was obtained 17 months after surgery. Herein, we report this rare case of MiNEN of the papilla of Vater with lung metastasis.

Decreased neutrophil counts prolong inflammation in acute pancreatitis and cause inflammation spillover to distant organs.

BACKGROUND/OBJECTIVE: Acute pancreatitis is an aseptic inflammation caused by pathologically activated pancreatic enzymes and inflammatory mediators produced secondarily by neutrophils and other inflammatory cells and is one of the most difficult diseases to treat. This study aimed to investigate the role of neutrophils in pancreatitis by examining tissue dynamics. METHODS: We created a model of caerulein-induced pancreatitis in 12-week-old male granulocyte colony-stimulating factor knockout mice (G-CSF-KO) and wild-type littermate control mice (six intraperitoneal injections of caerulein [80 µg/kg body weight] at hourly intervals for 2 days). Mice were sacrificed 0, 3, 6, 12, 24, 36, 48, 72, and 168 h after caerulein administration and examined histologically. RESULTS: The survival rate after one week of caerulein administration was 100 % in the control mice, whereas it was significantly lower (10 %) in the G-CSF-KO mice. Histological examination revealed significant hemorrhage and inflammatory cell migration in the G-CSF-KO mice, indicating prolonged inflammation. CONCLUSION: Prolonged inflammation was observed in the G-CSF-KO mice. Tissue cleanup by neutrophils during the acute phase of inflammation may influence healing through the chronic phase.

Blood Purification in Patients with Sepsis Associated with Acute Kidney Injury: A Narrative Review.

Sepsis leads to organ dysfunction. Acute kidney injury, a common type of organ dysfunction, is associated with a high mortality rate in patients with sepsis. Kidney replacement therapy can correct the metabolic, electrolyte, and fluid imbalances caused by acute kidney injury. While this therapy can improve outcomes, evidence of its beneficial effects is lacking. Herein, we review the indications for blood purification therapy, including kidney replacement therapy, and the current knowledge regarding acute kidney injury in terms of renal and non-renal indications. While renal indications have been well-documented, indications for blood purification therapy in sepsis (non-renal indications) remain controversial. Excessive inflammation is an important factor in the development of sepsis; blood purification therapy has been shown to reduce inflammatory mediators and improve hemodynamic instability. Given the pathophysiology of sepsis, blood purification therapy may decrease mortality rates in these patients. Further trials are needed in order to establish the effectiveness of blood purification therapy for sepsis.

The endothelial glycocalyx-All the same? No, it is not.

The endothelial glycocalyx covers the lumen of blood vessels throughout the body and plays an important role in endothelial homeostasis. Advances in electron microscopy techniques have provided clues to better understand the structure and composition of identical vascular endothelial glycocalyx. The morphology and thickness of the endothelial glycocalyx differ from organ to organ. The content of the endothelial glycocalyx covering the vascular lumen differs even in the brain, heart, and lungs, which have the same continuous capillaries. Various types of inflammation are known to attenuate the endothelial glycocalyx; however, we found that the morphology of the glycocalyx damaged by acute inflammation differed from that damaged by chronic inflammation. Acute inflammation breaks the endothelial glycocalyx unevenly, whereas chronic inflammation leads to the overall shortening of the endothelial glycocalyx. The same drug has different effects on the endothelial glycocalyx, depending on the location of the target blood vessels. This difference in response may reflect not only the size and shape of the endothelial glycocalyx but also the different constituents. In the cardiac tissue, the expression of glypican-1, a core protein of the endothelial glycocalyx, was enhanced. By contrast, in the pulmonary tissue, the expression of heparan sulfate 6-O-sulfotransferase 1 and endothelial cell-specific molecule-1 significantly increased in the treatment group compared with that in the no-treatment group. In this review, we present the latest findings on the evolution of the vascular endothelial glycocalyx and consider the microstructural differences.

Corrigendum: Retrospective cohort study to determine the effect of preinjury antiplatelet or anticoagulant therapy on mortality in patients with major trauma.

[This corrects the article DOI: 10.3389/fmed.2022.1089219.].

Investigation of the relationship between intradialytic hypotension during hemodialysis and serum syndecan-1 concentration.

Intradialytic hypotension and arrhythmias are complications of hemodialysis. They are associated with decreased intravascular volume due to reduced ultrafiltration volume, cardiac function, and arterial tone. The vascular endothelial glycocalyx, which exists on the surface of healthy vascular endothelial cells and maintains vascular permeability, has been suggested to be impaired by hemodialysis. This single-center retrospective study evaluated the association between syndecan-1, an endothelial glycocalyx dysfunction marker, and complications of hemodialysis. We enrolled 92 patients who underwent outpatient hemodialysis at Gifu Seiryu Hospital from April to July 2022 (346 hemodialysis sessions). The median duration and time of hemodialysis were 40 months and 4.1 h, respectively. Median serum syndecan-1 levels were 67.7 ng/mL before and 98.3 ng/mL after hemodialysis. Hemodialysis complications were noted in 68 sessions, all of which were hypotension. No correlation between pre-hemodialysis syndecan-1 levels and the incidence of complications was observed. However, a positive correlation between the amount of change in syndecan-1 levels before and after hemodialysis and the incidence of hemodialysis complications was noted. Conversely, syndecan-1 levels did not correlate with brain or atrial natriuretic peptides, suggesting that impairment of the vascular endothelial glycocalyx may be a possible cause of intradialytic hypotension and may be useful in preventing intradialytic hypotension.

Tumor-resident regulatory T cells in pancreatic cancer express the αvß5 integrin as a targetable activation marker.

Pancreatic ductal adenocarcinoma (PDAC) has abundant immunosuppressive regulatory T cells (Tregs), which contribute to a microenvironment resistant to immunotherapy. Here, we report that Tregs in the PDAC tissue, but not those in the spleen, express the αvß5 integrin in addition to neuropilin-1 (NRP-1), which makes them susceptible to the iRGD tumor-penetrating peptide, which targets cells positive for αv integrin- and NRP-1. As a result, long-term treatment of PDAC mice with iRGD leads to tumor-specific depletion of Tregs and improved efficacy of immune checkpoint blockade. αvß5 integrin + Tregs are induced from both naïve CD4 + T cells and natural Tregs upon T cell receptor stimulation, and represent a highly immunosuppressive subpopulation of CCR8 + Tregs. This study identifies the αvß5 integrin as a marker for activated tumor-resident Tregs, which can be targeted to achieve tumor-specific Treg depletion and thereby augment anti-tumor immunity for PDAC therapy.