Hematopoietic Progenitor Cell Counts of the Leukapheresis Product Determined Using Sysmex XN Analyzers Predict a Sufficient Number of CD34+ Stem Cells in a Peripheral Blood Stem Cell Harvest for Autologous Transplantation.

Objective Several institutions outsource CD34+ cell counting of leukapheresis products, limiting rapid measurements, as results are obtained the next day. This problem is compounded with plerixafor use, a stem cell-mobilizing drug that increases leukapheresis efficiency but requires administration the day before leukapheresis. Use of this drug for a second leukapheresis procedure before the first-day leukapheresis CD34+ count results are confirmed causes unnecessary leukapheresis and expensive plerixafor administration. We investigated whether or not measuring hematopoietic progenitor cells in leukapheresis products (AP-HPCs) using a Sysmex XN-series analyzer could resolve this problem. Methods We retrospectively compared the absolute AP-HPC value per body weight with the CD34+ (AP-CD34+) count in 96 first-day leukapheresis product samples obtained between September 2013 and January 2021. Comparisons were also conducted according to regimen: granulocyte colony-stimulating factor (G-CSF) monotherapy, chemotherapy plus G-CSF, or plerixafor mobilization. Results AP-CD34+ and AP-HPC counts correlated strongly (rs=0.846) overall and, in particular, under chemotherapy plus G-CSF (rs=0.92) but correlated mildly under G-CSF monotherapy (rs=0.655). AP-HPCs could not completely be dichotomized based on an AP-CD34+ threshold of 2×106/kg for any stimulation procedure. In most cases with AP-HPCs >6×106/kg, the AP-CD34+ count exceeded 2.0×106/kg, but in 5.7% of these cases, the AP-CD34+ count was <2.0×106/kg. A cut-off of AP-HPCs >4.843×106/kg yielded a sensitivity of 71% and specificity of 96% for predicting AP-CD34+≥2×106/kg. Conclusion AP-HPCs can identify cases in which sufficient stem cells have been collected.

The perception of life and death in patients with end-of-life stage cancer: A systematic review of qualitative research.

PURPOSE: This study aims to clarify the perceptions on life and death among patients with the end-of-life stage cancer through a systematic review. METHODS: The search strategy combined MeSH terminology with free text searches, and was applied to the PubMed, CINAHL, Embase, and ICHUSHI (Japan Medical Abstracts Society) databases covering from 2010 to 5/2022. To ensure the quality of the research included, the Critical Appraisal Skills Program Qualitative Studies Checklist was used. Data relating to the perceptions of life and death of patients with the end-of-life stage cancer was extracted and analyzed with reference to qualitative meta-synthesis methods. RESULTS: Ultimately, 50 studies were included. Five themes were derived based on the perceptions of life and death of patients with the end-of-life stage cancer: despair, making sense of death, how to live the rest of life, special feelings for loved ones, and fluctuation. By making sense of death in their own way, and reconciling it with their current situation, patients with the end-of-life stage cancer, even in despair over their impending death, look ahead into the future and their surroundings and consider how they would live the remaining time they have. During this time, the special feelings they have for their loved ones make an impact. CONCLUSIONS: An important new finding from this study lies in the fact that the patients' desire to live as ordinary people who were not patients were expressed as a face that they hid from their families. Further research is needed in low-income countries/regions.

[A Case of Locally Advanced, Unresectable Pancreatic Cancer with Superior Mesenteric Artery Invasion Treated with FOLFIRINOX plus Radiation Therapy, followed by Conversion Surgery].

We report a case of a woman in her 70s who underwent conversion surgery after FOLFIRINOX, followed by radiation therapy for initially locally advanced unresectable pancreatic cancer. She visited her local doctor with a chief complaint of upper abdominal pain. Contrast-enhanced CT scan of the abdomen revealed an irregular mass invading the superior mesenteric artery, and the first and second jejunal arteries(>180°)in the pancreatic uncinate region. Based on imaging, she was diagnosed as UR-LA(sm), cT4N0M0, cStage Ⅲ pancreatic cancer, and underwent 5 courses of modified FOLFIRINOX. Radiation therapy of 50.4 Gy was added for local control, and CA19-9 decreased from 394.1 U/mL to 10.5 U/mL. The treatment effect was judged as RECIST: partial response. The tumor was considered to be potentially curative, and a subtotal stomach preserving pancreaticoduodenectomy was performed 8 months after the initial treatment. The tumor was found to be 3× 2 mm in size, pStage ⅠA, R0, and the response to preoperative chemotherapy: Evans Grade Ⅲ. The patient is alive at 5 months postoperatively without recurrence.

[A Case of Local Recurrent Liver Metastasis from Sigmoid Colon Cancer after Complete Histological Remission, Treated with Rehepatectomy].

We report a case of a patient with sigmoid colon cancer and multiple liver metastases who underwent hepatectomy after chemotherapy and pathological results showed complete remission. However, after chemotherapy was discontinued, the patient developed a local recurrence of the liver metastasis and underwent rehepatectomy. The patient came to our hospital with lower abdominal pain. Colonoscopy revealed a circumferential type Ⅱ, well-differentiated adenocarcinoma. Laparoscopic sigmoidectomy with lymph node dissection was performed. Postoperative CT scan showed multiple liver metastases at S5, S7, and S8. 11 cycles of bevacizumab plus modified FOLFOX(mFOLFOX)were subsequently performed. The liver metastases shrank at all sites, and the patient underwent right hepatectomy. The resected specimen was considered to be in complete remission, with no evidence of viable malignant cells. Postoperatively, bevacizumab plus mFOLFOX was resumed for 6 cycles and the patient remained in remission. However, 3 months after stopping chemotherapy and 1 year and 6 months after hepatectomy, a follow-up CT scan showed local recurrence of the liver edge, and a diagnosis of local recurrence of liver metastasis was made, and a partial hepatectomy was performed. The patient is recurrence-free and resuming modified FOLFOX 9 months after surgery.

Discordance between hyposalivation and xerostomia among community-dwelling older adults in Japan.

Individuals with an objective decrease in salivary flow (objective dry mouth) may not be aware of subjective dry mouth (xerostomia). However, no clear evidence exists to explain the discordance between subjective and objective dry mouth. Therefore, this cross-sectional study aimed to assess the prevalence of xerostomia and decreased salivary flow among community-dwelling elderly adults. In addition, this study assessed several potential demographic and health status determinants of the discrepancy between xerostomia and reduced salivary flow. The 215 participants in this study were community-dwelling older people aged 70 years and above who underwent dental health examinations between January-February 2019. Symptoms of xerostomia were collected in the form of a questionnaire. The unstimulated salivary flow rate (USFR) was measured by a dentist using visual inspection. The stimulated salivary flow rate (SSFR) was measured using the Saxon test. We identified 19.1% of participants as having mild-severe USFR decline with xerostomia and 19.1% as having mild-severe USFR decline without xerostomia. Additionally, 26.0% of participants had low SSFR and xerostomia, and 40.0% had low SSFR without xerostomia. Except for the age trend, no factors could be associated with the discordance between USFR measurement and xerostomia. Furthermore, no significant factors were associated with the discordance between the SSFR and xerostomia. However, females were significantly associated (OR = 2.608, 95% CI = 1.174-5.791) with low SSFR and xerostomia, as compared to males. Age was a factor that was also significantly associated (OR = 1.105, 95% CI = 1.010-1.209) with low SSFR and xerostomia. Our findings indicate that approximately 20% of the participants had low USFR without xerostomia, and 40% had low SSFR without xerostomia. This study showed that age, sex, and the number of medications may not be factors in the discrepancy between the subjective feeling of dry mouth and reduced salivary flow.

Rolling removal technique for a tick embedded in the eyelid.

We present the case of a 5-year-old girl with a tick bite on the left upper eyelid margin. We introduce a rolling removal technique using the scleral plug forceps.

A case of Vp4 hepatocellular carcinoma with tumor thrombosis extending into the confluence of the splenic/portal vein achieved a good prognosis with emergent hepatectomy and postoperative adjuvant therapy with lenvatinib.

In this report, we describe a case of highly advanced hepatocellular carcinoma with tumor thrombosis extending into the main portal vein of the pancreas that was successfully treated with adjuvant lenvatinib after right hepatic resection with thrombectomy. A 70-year-old woman was referred from the clinic because of elevated hepatobiliary enzymes. The patient was positive for the hepatitis B virus antigen at our hospital. The tumor markers were highly elevated with alpha-fetoprotein (14.5 U/mL) and protein induced by vitamin K absence (PIVKAII) (1545 ng/mL), suggesting hepatocellular carcinoma. Dynamic abdominal computed tomography showed an early enhanced tumor approximately 6 cm in size and portal vein tumor thrombosis filling the main portal vein, but not extending into the splenic or superior mesenteric vein (SMV). On magnetic resonance imaging 1 week after CT, portal vein tumor thrombosis had extended to the confluence of the splenic vein with the SMV, indicating rapid tumor growth. Thus, we performed emergent right hepatectomy with tumor thrombectomy. Postoperatively, we treated the patient with lenvatinib for a tumor reduction surgery. Fortunately, the patient was alive 2 years postoperatively without recurrence. This case report suggests that a favorable outcome may be achieved with multidisciplinary treatment including resection and postoperative treatment with lenvatinib.

[A Case of Resection of Pancreatic Body Cancer Successfully Treated with GEM plus Nab-PTX].

The case was a 72-year-old man who had been on medication due to chronic pancreatitis since 2009 and was referred to our hospital because dilation of the main pancreatic duct was shown by abdominal ultrasonography. The contrast CT scan of the abdomen showed a 30 mm in size, poorly enhanced tumor at the body of the pancreas, which was suspected to invasion the celiac artery, common hepatic artery, and splenic artery. EUS showed a hypoechoic tumor with a diameter of 29× 24 mm. ERCP showed disruption of the pancreatic duct in the body of the pancreas, and cytological examination of the pancreatic juice showed a suspicious positive result. We diagnosed unresectable locally advanced pancreatic cancer in the body of the pancreas and underwent chemotherapy(gemcitabine plus nab-paclitaxel: GnP). Contrast-enhanced CT after 6 courses of GnP showed tumor shrinkage. FDG-PET/CT revealed a slightly in fluorine-18-deoxyglucose(FDG)accumulation in the tumor, but no accumulation around the blood vessels. Based on the above, it was judged that the tumor was possible radical resection, and surgery was performed. Intraoperative frozen section examination revealed no malignant findings in the tissues surrounding the main artery near the pancreatic body cancer, and distal pancreatectomy was performed. Histopathologically, the tumor showed findings of tubular adenocarcinoma, and the histological response to neoadjuvant therapy was Grade 2. We report a case in which conversion surgery was possible by chemotherapy.

The usefulness of preoperative exocrine function evaluated by the 13C-trioctanoin breath test as a significant physiological predictor of pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: The association between pancreatic fistula (PF) after pancreaticoduodenectomy (PD) and preoperative exocrine function is yet to be elucidated. This study aimed to evaluate the association between the preoperative results of the 13C-trioctanoin breath test and the occurrence of PF, showing the clinical relevance of the breath test in predicting PF. METHOD: A total of 80 patients who underwent 13C-trioctanoin breath tests prior to PD from 2006 to 2018 were included in this study. Univariate and multivariate analyses were conducted to reveal the preoperative predictors of PF, showing the association between 13C-trioctanoin absorption and PF incidence. RESULTS: Among 80 patients (age, 68.0 ± 11.9 years, 46 males and 34 females; 30 pancreatic ductal adenocarcinoma [PDAC]/50 non-PDAC patients), the incidence of PF was 12.5% (10/80). Logistic regression analysis results revealed that the frequency of PF increased significantly as the 13C-trioctanoin breath test value (Aa% dose/h) increased (odd's ratio: 1.082, 95% confidence interval: 1.007-1.162, p = 0.032). Moreover, the optimal cutoff value of the preoperative fat absorption level to predict PF was 38.0 (sensitivity, 90%; specificity, 74%; area under the curve, 0.78; p = 0.005). Indeed, the incidence of PF was extremely higher in patients whose breath test value was greater than 38.0 (33%, 9/27) compared with that in patients with values less than 38.0 (1.8%, 1/53). CONCLUSIONS: Favorable preoperative fat absorption evaluated using the 13C-trioctanoin breath test is a feasible and objective predictor of PF after PD.

A preserved pancreatic exocrine function after pancreatectomy may be a crucial cause of pancreatic fistula: paradoxical results of the 13C-trioctanoin breath test in the perioperative period.

PURPOSE: The aim of this study was to elucidate the association between pancreatic fistula (PF) and the sequential changes in the perioperative exocrine function after pancreatectomy. METHODS: The subjects were 96 patients who underwent a 13C-trioctanoin breath test before and 1 month after pancreatectomy, between 2006 and 2018. We retrospectively compared the pre- and postoperative fat absorption levels between patients with PF (PF group; n = 17) and without PF (non-PF group; n = 79) using the breath test. RESULTS: The preoperative level of 13C-trioctanoin absorption (%dose/h) was comparable between the non-PF and PF groups (36.5 vs. 36.9). In the non-PF group, 13C-trioctanoin absorption was significantly decreased after surgery in comparison to the preoperative setting (post-operative 28.5; pre-operative 36.5; p < 0.0001), whereas these values were comparable (post-operative 36.9; pre-operative 34.5; p = 0.129) in the PF group. Moreover, postoperative absorption in the PF group was significantly better than that in the non-PF group (34.5 vs. 28.5%, p = 0.0003). The maximum drain amylase level was significantly higher in patients with a 13C-trioctanoin absorption level (%dose/h) of ≥ 30 in comparison to patients with levels of < 30 (2502 vs. 398 U/L, p = 0.001). CONCLUSION: PF did not exacerbate the pancreatic exocrine function in the early postoperative period, and the acceleration or preservation of the exocrine function after surgery may be an important cause of PF.

Modified Socratic Method (planned and executed by Takada) for medical education: Grade II Acute Cholecystitis of Tokyo Guidelines 2018 as an example case.

BACKGROUND: Socratic method, which is an educational method to promote critical thinking through a dialogue, has never been practiced in a large number of people at the academic societies. METHODS: Modified Socratic method was performed for the first time as an educational seminar using an example case of moderate acute cholecystitis based on the evidence described in Tokyo Guidelines 2018. We adopted a method that Takada had been modifying for many years: the instructor first knows the degree of recognition of the audience, then the instructor gives a lecture in an easy-to-understand manner and receives questions from the audience, followed by repeated questions and answers toward a common recognition. RESULTS: Using slides, video, and an answer pad, 281 participants including the audience, instructors and moderators came together to repeatedly ask and answer questions in the five sessions related to the case scenario. The recognition rate of the topic of Critical View of Safety increased significantly before vs after this method (53.0% vs 90.3%). The seminar had been successfully performed by receiving a lot of praise from the participants. CONCLUSION: This educational method is considered to be adopted by many academic societies in the future as an effective educational method.

Surgery for pancreatic tumors in the midst of COVID-19 pandemic.

The spread of the new coronavirus (COVID-19) infection in 2020 has had a significant impact on the treatment of cancer worldwide. During the COVID-19 pandemic, the biggest challenge for pancreatic surgeons is the difficulty in providing oncological care. In this review article, from the standpoint of surgeons, we explain the concept of triaging of patients with pancreatic tumors under the COVID-19 pandemic, and the actual impact of COVID-19 on the treatment of patients with pancreatic tumors. The most vital points in selecting the best therapeutic approach for patients with pancreatic tumors during this pandemic are (1) Oncologists need to tailor the treatment plan based on the COVID-19 phase, tumor malignant potential, and patients' comorbidities; and (2) Optimal treatment for pancreatic cancer should be planned according to the condition of each patient and tumor resectability based on national comprehensive cancer network resectability criteria. To choose the best therapeutic approach for patients with pancreatic tumors during this pandemic, we need to tailor the treatment plan based on elective surgery acuity scale (ESAS). Newly established ESAS for pancreatic tumor and flowchart indicating the treatment strategy of pancreatic cancer, are feasible to overcome this situation.

[Relationship between the number of prescribed medications and oral dysfunction in elderly individuals].

Objective　Polypharmacy in elderly individuals may cause reduced flow of saliva and xerostomia. A dry mouth can lead to poor oral function; however, there are no reports on the relationship between polypharmacy and subjective or objective oral dysfunction. The purpose of this study was to clarify the relationship between the number of prescribed medications and subjective and objective oral dysfunction.Methods　The subjects of this study were 215 community-dwelling, elderly individuals, aged 75 years or older, who visited the dental clinic in the Chubu region for a dental health examination from January to February 2019. A medical interview was conducted to assess three items that were related to subjective oral function and record four measurements related to objective oral function. In addition, information was collected on the diseases being treated and prescribed medications. A subject with a decrease in any of the three subjective oral function categories was considered to have subjective oral dysfunction. Objective oral dysfunction was analyzed with respect to two types of oral dysfunction: a decrease in all four objective oral functions and a decrease in two or more of the four objective oral functions. Logistic regression analysis was performed to examine the relationship between subjective and objective oral dysfunction after adjustment for sex, age group, inveterate disease, and the number of prescribed medications.Results　Individuals who had eight or more prescribed medications had lower subjective oral function than those with seven or fewer medications (odds ratio, 95% confidence interval: 2.3, 1.0-5.1; P<0.05). Individuals with eight or more medications had lower scores in all four objective oral functions than those with seven or fewer medications (4.4 : 1.5-12.6, P<0.01). A decrease in two or more of the four objective oral functions was related to 10 or more prescribed medications (4.3 : 1.2-16.2, P<0.05).　In addition, taking eight or more prescribed medications was associated with a decrease in either subjective oral function or all four objective oral functions (8.1 : 2.1-30.8, P<0.01). A decrease in either subjective oral function or two or more objective oral functions was related to taking 10 or more prescribed medications (4.9 : 1.6-15.6, P<0.01).Conclusion　In conclusion, more than eight prescribed pharmaceutical medications in the elderly is associated with subjective or objective oral dysfunction.

Resection of pancreatic and splenic metastases from alveolar soft part sarcoma: a case report.

BACKGROUND: We present a case of pancreatic and splenic metastases following alveolar soft part sarcoma (ASPS), which was successfully treated by surgery. CASE PRESENTATION: A 41-year-old male was referred to our hospital in 2012. Computed tomography (CT) showed the presence of a pancreatic tumor. In 2002, the patient had undergone surgical resection of an ASPS of the anal region. In 2009, during follow-up, CT revealed lung metastases, which prompted surgical resection of the lung, followed by resection of the head skin in 2011. Abdominal ultrasonography (US) revealed the presence of isodense masses sized 34 mm in the pancreatic head and 60 mm within the spleen. The contrast-enhanced US revealed a solitary lesion with enhancement. Contrast-enhanced CT revealed solitary lesions with enhancement within the pancreatic head, spleen, and liver. The patient underwent metastasectomies from the pancreas, spleen, and liver. The patient was discharged on postoperative day 22 without recurrence for 18 months after metastasectomy. Twelve years after primary resection and 2 years after metastasectomy, the patient died as a consequence of multiple metastases. CONCLUSIONS: We have presented a rare case of pancreatic and spleen metastases from ASPS. Resection by radical metastasectomy was successful without morbidity. Thus, for improved survival of patients with multiple metastases from ASPS, metastasectomy may be indicated. If multiple metastases are resectable, surgical approaches may be the preferred treatment.

A case of hepatocellular adenoma with pedunculated development and difficulty in diagnosis.

Hepatocellular adenoma (HCA) is a benign hepatocyte-derived epithelial tumor. HCA is associated with oral contraceptive use among Caucasian populations. We report a case of hepatocellular adenoma with a pedunculated protuberance and high protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels, which made diagnosis challenging. The patient was a 22-year-old woman. In a medical check-up, a high γ-GTP level was detected and a 115-mm solid mass was found in her lower abdomen via abdominal ultrasonography. A blood test showed a high PIVKA-II level. Abdominal CT showed a tumor in the lower abdomen. Contrast-enhanced CT showed a blood vessel thought to be the left hepatic artery connecting to the mass, and a blood vessel thought to be the left hepatic vein returning from the mass to the inferior vena cava. In EOB-MRI, uneven enhancement was observed after contrast imaging, but washout in the equilibrium phase was unclear. Parenchymal hepatocyte phases showed a pale, non-uniform, high signal. These findings indicated that the tumor was derived from the left lobe of the liver and was suggestive of HCC. Surgical resection was then performed. A pathological examination led to a diagnosis of HCA, corresponding to unclassified HCA. The WHO classification of tumors of the digestive system based on an immunohistological examination includes HNF1α-inactivated HCA, ß-catenin-activated HCA, inflammatory HCA, and unclassified HCA. In summary, our patient had a large HCA with pedunculated protrusion into the extrahepatic pelvic cavity. This case was challenging to diagnose because of abnormally high PIVKA-II levels, and it was resected laparoscopically.

Arterial shear stress reduces eph-b4 expression in adult human veins.

Vein graft adaptation to the arterial environment is characterized by loss of venous identity, with reduced Ephrin type-B receptor 4 (Eph-B4) expression but without increased Ephrin-B2 expression. We examined changes of vessel identity of human saphenous veins in a flow circuit in which shear stress could be precisely controlled. Medium circulated at arterial or venous magnitudes of laminar shear stress for 24 hours; histologic, protein, and RNA analyses of vein segments were performed. Vein endothelium remained viable and functional, with platelet endothelial cell adhesion molecule (PECAM)-expressing cells on the luminal surface. Venous Eph-B4 expression diminished (p = .002), Ephrin-B2 expression was not induced (p = .268), and expression of osteopontin (p = .002) was increased with exposure to arterial magnitudes of shear stress. Similar changes were not found in veins placed under venous flow or static conditions. These data show that human saphenous veins remain viable during ex vivo application of shear stress in a bioreactor, without loss of the venous endothelium. Arterial magnitudes of shear stress cause loss of venous identity without gain of arterial identity in human veins perfused ex vivo. Shear stress alone, without immunologic or hormonal influence, is capable of inducing changes in vessel identity and, specifically, loss of venous identity.

Polymorphobacter multimanifer gen. nov., sp. nov., a polymorphic bacterium isolated from Antarctic white rock.

A Gram-stain-negative, non-spore-forming, aerobic, oligotrophic bacterium (strain 262-7(T)) was isolated from a crack of white rock collected in the Skallen region of Antarctica. Strain 262-7(T) grew at temperatures between -4 and 30 °C, with optimal growth at 25 °C. The pH range for growth was between pH 6.0 and 9.0, with optimal growth at approximately pH 7.0. The NaCl concentration range allowing growth was between 0.0 and 1.0%, with an optimum of 0.5%. Strain 262-7(T) showed an unprecedented range of morphological diversity in response to growth conditions. Cells grown in liquid medium were circular or ovoid with smooth surfaces in the lag phase. In the exponential phase, ovoid cells with short projections were observed. Cells in the stationary phase possessed long tentacle-like projections intertwined intricately. By contrast, cells grown on agar plate medium or in liquid media containing organic compounds at low concentration exhibited short- and long-rod-shaped morphology. These projections and morphological variations clearly differ from those of previously described bacteria. Ubiquinone 10 was the major respiratory quinone. The major fatty acids were C(17 : 1)ω6c (28.2%), C(16 : 1)ω7c (22.6%), C(18 : 1)ω7c (12.9%) and C(15 : 0) 2-OH (12.3%). The G+C content of genomic DNA was 68.0 mol%. Carotenoids were detected from the cells. Comparative analyses of 16S rRNA gene sequences indicated that strain 262-7(T) belongs to the family Sphingomonadaceae, and that 262-7(T) should be distinguished from known genera in the family Sphingomonadaceae. According to the phylogenetic position, physiological characteristics and unique morphology variations, strain 262-7(T) should be classified as a representative of a novel genus of the family Sphingomonadaceae. Here, a novel genus and species with the name Polymorphobacter multimanifer gen. nov., sp. nov. is proposed (type strain 262-7(T) = JCM 18140(T) = ATCC BAA-2413(T)). The novel species was named after its morphological diversity and formation of unique projections.

The Nogo-B-PirB axis controls macrophage-mediated vascular remodeling.

OBJECTIVE: Nogo-B mediates vascular protection and facilitates monocyte- and macrophage-dependent vascular remodeling. PirB is an alternate receptor for Nogo-B, but a role for the Nogo-PirB axis within the vascular system has not been previously reported. We examined whether Nogo-B or PirB play a role in regulating macrophage-mediated vascular remodeling and hypothesized that endothelial Nogo-B regulates vein graft macrophage infiltration via its alternate receptor PirB. METHODS: Vein grafts were performed using Nogo and PirB wild type and knockout mice. Human vein grafts were similarly analyzed. The hindlimb ischemia model was performed in PirB wild type and knockout mice. Accompanying in vitro work included isolation of macrophages from PirB wild type and knockout mice. RESULTS: Increased Nogo-B and PirB mRNA transcripts and protein expression were observed within mouse and human vein grafts. Both Nogo knockout and PirB knockout vein grafts showed increased wall thickness and increased numbers of F4/80-positive macrophages. Macrophages derived from PirB knockout mice had increased adhesion to fibronectin, increased EC-specific binding, and increased numbers of mRNA transcripts of M2 markers as well as MMP3 and MMP9. PirB knockout vein grafts had increased active MMP9 compared to wild type vein grafts. PirB knockout mice had increased recovery from hindlimb ischemia and increased macrophage infiltration compared to wild type mice. CONCLUSIONS: Vein graft adaptation shows increased expression of both Nogo-B and PirB. Loss of PirB, or its endothelial ligand Nogo-B, results in increased inflammatory cell infiltration and vein graft wall thickening. These findings suggest that PirB regulates macrophage activity in vein grafts and that Nogo-B in the vein graft limits macrophage infiltration and vein graft thickening. PirB may play a more general role in regulating macrophage responses to vascular injury. Macrophage inhibition via Nogo-PirB interactions may be an important mechanism regulating vein graft adaptation to the arterial circulation.