Inositol pyrophosphate profiling reveals regulatory roles of IP6K2-dependent enhanced IP7 metabolism in the enteric nervous system.

Inositol pyrophosphates regulate diverse physiological processes; to better understand their functional roles, assessing their tissue-specific distribution is important. Here, we profiled inositol pyrophosphate levels in mammalian organs using an originally designed liquid chromatography-mass spectrometry (LC-MS) protocol and discovered that the gastrointestinal tract (GIT) contained the highest levels of diphosphoinositol pentakisphosphate (IP7) and its precursor inositol hexakisphosphate (IP6). Although their absolute levels in the GIT are diet dependent, elevated IP7 metabolism still exists under dietary regimens devoid of exogenous IP7. Of the major GIT cells, enteric neurons selectively express the IP7-synthesizing enzyme IP6K2. We found that IP6K2-knockout mice exhibited significantly impaired IP7 metabolism in the various organs including the proximal GIT. In addition, our LC-MS analysis displayed that genetic ablation of IP6K2 significantly impaired IP7 metabolism in the gut and duodenal muscularis externa containing myenteric plexus. Whole transcriptome analysis of duodenal muscularis externa further suggested that IP6K2 inhibition significantly altered expression levels of the gene sets associated with mature neurons, neural progenitor/stem cells, and glial cells, as well as of certain genes modulating neuronal differentiation and functioning, implying critical roles of the IP6K2-IP7 axis in developmental and functional regulation of the enteric nervous system. These results collectively reveal an unexpected role of mammalian IP7-a highly active IP6K2-IP7 pathway is conducive to the enteric nervous system.

Foxc1 and Foxc2 are indispensable for the maintenance of nephron and stromal progenitors in the developing kidney.

Nephron development proceeds with reciprocal interactions among three layers: nephron progenitors (NPs), ureteric buds and stromal progenitors (SPs). We found that Foxc1 and Foxc2 (Foxc1/2) are expressed in NPs and SPs. Systemic deletion of Foxc1/2 2 days after the onset of metanephros development (embryonic day 13.5) resulted in the epithelialization of NPs and ectopic formation of renal vesicles. NP-specific deletion did not cause these phenotypes, indicating that Foxc1/2 in other cells (likely in SPs) contributed to the maintenance of NPs. Single-cell RNA-sequencing analysis revealed the existence of NP and SP subpopulations, the border between committed NPs and renewing NPs, and similarity between the cortical interstitium and vascular smooth muscle type cells. Integrated analysis of the control and Foxc1/2 knockout data indicated transformation of some NPs to strange cells expressing markers of the vascular endothelium, reduced numbers of self-renewing NP and SP populations, and downregulation of crucial genes for kidney development, such as Fgf20 and Frem1 in NPs, and Foxd1 and Sall1 in SPs. It also revealed upregulation of genes that were not usually expressed in NPs and SPs. Thus, Foxc1/2 maintain NPs and SPs by regulating the expression of multiple genes.

Comparison Between Plastic and Metallic Biliary Stent Placement for Preoperative Patients with Pancreatic Head Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Optimal preoperative biliary drainage for patients with pancreatic cancer before pancreatoduodenectomy remains unclear. This study aimed to investigate the comparison of efficacy and safety between a metallic stent (MS) and a plastic stent (PS). METHODS: Comparative studies on the use of MS and PS for pancreatic cancer before pancreatoduodenectomy were systematically searched using the MEDLINE and Web of Science databases. Pre- and postoperative data also were extracted. Random-effects meta-analyses were performed to compare post-endoscopic retrograde cholangiopancreatography (ERCP) complications as well as intra- and postoperative outcomes between the two arms of the study, and pooled odds ratios (ORs) or mean differences (MDs) were calculated with 95 percent confidence intervals (CIs). RESULTS: The study analyzed 12 studies involving 683 patients. Insertion of MS was associated with a lower incidence of re-intervention (OR, 0.06; 95% CI 0.03-0.15; P < 0.001), increased post-ERCP adverse events (OR, 2.22; 95% CI 1.13-4.36; P = 0.02), and similar operation time (MD, 18.0 min; 95% CI -29.1 to 65.6 min; P = 0.46), amount of blood loss (MD, 43.0 ml; 95% CI -207.1 to 288.2 ml; P = 0.73), and surgical complication rate (OR, 0.78; 95% CI 0.53-1.15; P = 0.21). The cumulative stent patency rate after 3 months was higher in the MS group than in the PS group (70-100 % vs 30.0-45.0 %). CONCLUSION: For biliary drainage in patients with pancreatic cancer during this era of multidisciplinary treatment, MS use might be the first choice because MS provides a more durable biliary drainage and a similar risk of postoperative outcomes compared with PS.

Sulfamethoxazole-trimethoprim for pneumocystis pneumonia prophylaxis, causes of discontinuation and thrombocytopenia observed during administration: A single-center retrospective study.

INTRODUCTION: The development of pneumocystis pneumonia (PCP) has recently become a growing concern; thus, its prevention has become increasingly important. Sulfamethoxazole-trimethoprim (ST) is a cost-effective first-line and prophylactic treatment for PCP. However, ST administration criteria for PCP prophylaxis remain unclear and are often discontinued because of adverse events (AEs). In this study, we aimed to investigate the causes of ST discontinuation and the associated AEs using objective data. METHODS: We retrospectively analyzed the data of 162 patients admitted to Kansai Medical University Hospital between January 2018 and December 2020, who received ST for PCP prophylaxis. We compared clinical characteristics, laboratory data, and incidence of AEs between ST non-discontinuation and ST discontinuation groups. Additionally, we divided the patients into non-developing and developing thrombocytopenia (≥ Grade 1) groups based on the investigation results. RESULTS: No patients developed PCP while receiving ST. The most common causes of ST discontinuation were thrombocytopenia (37%), liver dysfunction (20%), and rash (18%). Multivariate analysis revealed thrombocytopenia (≥ Grade 1) as a factor significantly associated with ST discontinuation. Furthermore, we identified three factors correlated with thrombocytopenia (≥ Grade 1): age ≥50 years, lymphocyte count <1000/µL, and platelet count <180,000/µL. CONCLUSIONS: Patients with the aforementioned factors are at higher risk of developing thrombocytopenia (≥ Grade 1) during ST administration for PCP prophylaxis. Therefore, platelet count monitoring is essential to enhance safety and efficacy of ST treatment. Nonetheless, further research is warranted to explore additional implications and interventions.

Relationship between cleaning frequency and pressure ulcer healing time in older people receiving home care.

OBJECTIVE: The relationship between the healing time of pressure ulcers (PUs) and wound cleaning frequency among older people in homecare settings was investigated. METHOD: This single-centre, prospective cohort study was conducted from April 2018 to March 2019. Patients who used home-visit nursing services, had National Pressure Ulcer Advisory Panel classification stage 2 PUs, and had their wounds cleaned at least twice a week were enrolled in the study. Wound cleaning was performed using tap water and a weakly acidic cleanser. Participants were divided into two groups, determined by the frequency of wound cleaning (twice weekly versus ≥3 times weekly). Duration of PU healing and the increase in care insurance premiums were compared in both groups. RESULTS: A total of 12 patients were included in the study. The mean healing period of PUs cleaned ≥3 times per week (65.3±24.8 days) was significantly shorter than that of PUs cleaned twice a week (102.6±19.2 days; p<0.05). Furthermore, the increase in care insurance premiums for PUs cleaned ≥3 times per week (¥122,497±105,660 Yen per six months) was significantly lower than that for PUs cleaned twice a week (¥238,116±60,428 per six months) (p<0.05). CONCLUSION: Our results suggest that frequent cleaning of PUs by health professionals in homecare settings not only shorten PU healing period but also reduces care insurance premiums for PU care.

Standardized upfront Glissonean approach and liver hanging maneuver reduces bile leakage from the hepatic hilum in living donors.

Biliary complications after hepatectomy in living donors have yet to be eradicated. We hypothesized that a standardized upfront Glissonean approach and liver hanging maneuver (GH) would prevent mechanical and thermal injuries to the hilar plate of the remnant liver by determining the point of bile duct division and the final destination of hepatectomy preceding liver parenchymal transection (safety) and facilitate liver transection deep within the parenchyma and allow maximum length of hilar structures (rationality). GH was implemented in 2016 and its incidence of bile leakage was retrospectively compared against the conventional technique. GH comprises six steps: (1) development of the retrohepatic avascular plane between the right hepatic vein (RHV) and the middle hepatic vein (MHV) and isolation of the hepatic vein(s); (2) isolation of the right or left Glissonean pedicle with the corresponding Glissonean pedicles of the caudate lobe; (3) for right liver grafts and left liver grafts with the caudate lobe, passage of the tape for the liver hanging maneuver along the retrohepatic avascular plane and above the hilar plate, and for left liver grafts without the caudate lobe and for left lateral section grafts, passage of the tape from between the RHV and the MHV, along the Arantius ligament, and to the right of the umbilical portion; (4) liver transection; (5) isolation of hilar structures; and (6) graft procurement. Until 2020, 62 consecutive living donors underwent GH (success rate, 100%). The incidence of bile leakage from the hepatic hilum (0%) was significantly lower than that among 59 donors who underwent the conventional technique in 2011-2015 (9%; p = 0.01). In conclusion, GH is highly effective in reducing bile leakage from the hepatic hilum in living donors.

Induction Chemotherapy with FOLFIRINOX for Locally Advanced Pancreatic Cancer: A Simple Scoring System to Predict Effect and Prognosis.

BACKGROUND: Effective chemotherapy (CTx) protocols as induction treatment provide increasing opportunities for surgical resection of locally advanced pancreatic cancer (LAPC). Although improved survival after resection of LAPC with CTx has been reported for selected patients, reliable recommendations on the indication for conversion surgery after induction treatment are currently lacking. We investigated the factors predictive of prognosis in resected LAPC after FOLFIRINOX. METHODS: Consecutive patients with LAPC undergoing curative resection after FOLFIRINOX between 2011 and 2018 were identified from a prospectively maintained database. Relevant clinical parameters and CT findings were examined. A scoring system was developed based on the ratio of hazard ratios for overall survival of all significant predictors. RESULTS: A total of 62 patients with LAPC who underwent oncologic resection after FOLFIRINOX were analyzed. Tumor shrinkage, tumor density, and postchemotherapy CA19-9 serum levels were independently associated with overall survival (multivariate analysis: HR = 0.31, 0.17, and 0.18, respectively). One, two, and two points were allocated to these three factors in the proposed scoring system, respectively. The median overall survival of patients with a score from 0 to 2 was significantly shorter than that of patients with a score from 3 to 5 (22.1 months vs. 53.2 months, P < 0.001). CONCLUSIONS: Tumor density is a novel predictive marker for the prognosis of patients with resected LAPC after FOLFIRINOX. A simple scoring model incorporating tumor density, the tumor shrinkage rate, and CA 19-9 levels identifies patients with a low score, who may be candidates for additional treatment.

ROS1 as a possible prognostic biomarker of cervical adenocarcinoma: An exploratory analysis with next-generation sequencing.

OBJECTIVES: Given the differences in clinical and biological characteristics between cervical adenocarcinoma and squamous cell carcinoma, this study aimed to conduct an exploratory analysis to examine the molecular characteristics of cervical adenocarcinoma in a Japanese population. METHODS: This study explored the simultaneous testing of multiple mutations targeting cervical adenocarcinoma using next-generation sequencing (NGS). The following genes were analyzed: BCAR4, CD274, PDCD1LG2, KRAS, ARID1A, PTEN, ALK, EGFR, ROS1, BRAF, PIK3CA, EP300, EBXW7, SHCBP1, TGFBR2, SMAD4, ERBB2, ERBB3, and KLF5. Tumor tissue and blood samples were obtained at the time of primary treatment. The NGS-based molecular profiles obtained from Tokai University (49 specimens) were compared with the registered data in The Cancer Genome Atlas (TCGA) database (133 specimens). RESULTS: The study cohort had higher rates of adenocarcinoma than the TCGA cohort (44.9% vs. 18.0%; P = 0.001). The adenocarcinomas in the study cohort had more alterations in ROS1, EGFR, EP300, SHCBP1, ALK, and PIK3CA than those in the TCGA cohort. Among them, ROS1 had the highest number of gene alterations (median, 7.00 ± 2.63). In the study cohort, patients with a high number of ROS1 alterations had a significantly higher recurrence rate (5-year recurrence rate, 48.8% vs. 14.6%; hazard ratio [HR], 4.32; 95% confidence interval [CI], 1.20-15.50; P = 0.014) and lower overall survival than those with low alterations (5-year survival rate, 70.7% vs. 93.1%; HR, 7.15; 95% CI, 1.08-58.22; P = 0.032). CONCLUSION: The current exploratory analysis suggests that ROS1 gene alteration may be a prognostic biomarker in cervical adenocarcinoma in Japanese patients.

Proteomic profiling of sudden cardiac death with acquired cardiac hypertrophy.

BACKGROUND: Cardiac hypertrophy, which develops in middle-aged and older individuals as a consequence of hypertension and obesity, is an established risk factor for sudden cardiac death (SCD). However, it is sometimes difficult to differentiate SCD with acquired cardiac hypertrophy (SCH) from compensated cardiac hypertrophy (CCH), at autopsy. We aimed to elucidate the proteomic alteration in SCH, which can be a guideline for future postmortem diagnosis. METHODS: Cardiac tissues were sampled at autopsy. SCH group consisted of ischemic heart failure, hypertensive heart failure, and aortic stenosis. CCH group included cases of non-cardiac death with cardiac hypertrophy. The control group comprised cases of non-cardiac death without cardiac hypertrophy. All patients were aged > 40 years, and hypertrophic cardiomyopathy was not included in this study. We performed histological examination and shotgun proteomic analysis, followed by quantitative polymerase chain reaction analysis. RESULTS: Significant obesity and myocardial hypertrophy, and mild myocardial fibrosis were comparable in SCH and CCH cases compared to control cases. The proteomic profile of SCH cases was distinguishable from those of CCH and control cases, and many sarcomere proteins were increased in SCH cases. Especially, the protein and mRNA levels of MYH7 and MYL3 were significantly increased in SCH cases. CONCLUSION: This is the first report of cardiac proteomic analysis in SCH and CCH cases. The stepwise upregulation of sarcomere proteins may increase the risk for SCD in acquired cardiac hypertrophy before cardiac fibrosis progresses significantly. These findings can possibly aid in the postmortem diagnosis of SCH in middle-aged and older individuals.

A Pediatric Case of Extraneural Subcutaneous Metastasis of Ependymoma.

Ependymoma is the third most common brain tumor in children. Extracranial metastases of ependymomas are uncommon. A 21-month-old Japanese boy was diagnosed to be brain dead due to a posterior fossa (PF) brain tumor. Surgical resection of the tumor was not performed. Twenty-seven months later, he developed a truncal subcutaneous tumor, which was pathologically diagnosed as PF ependymoma group A. We observed the intracranial recurrence of the brain tumor, an invasion to the left orbit, and a neoplasm in his liver before he died. This case suggests that PF ependymoma group A can metastasize extracranially to various organs.

Clinical characteristics and predictive factors of postoperative intra-abdominal abscess after distal pancreatectomy.

PURPOSE: The postoperative mortality rate of distal pancreatectomy is lower than that of pancreaticoduodenectomy, although persistent complications may occur after distal pancreatectomy. Fluid collection (FC) is frequently observed after distal pancreatectomy; however, FC may occasionally progress to postoperative intra-abdominal abscess (PIAA), which requires conservative or progressive interventional treatment. This study aimed to compare the status between patients with or without PIAA, identify predictive factors for PIAA and clinically relevant postoperative pancreatic fistula, and investigate the clinical characteristics of patients with PIAA with interventional drainage. METHODS: We retrospectively reviewed data of patients who underwent distal pancreatectomy between January 2012 and December 2019 at two high-volume centers, where hepatobiliary-pancreatic surgeries were performed by expert specialist surgeons. Logistic regression analysis was performed to determine the predictive factors for PIAA. RESULTS: Overall, 242 patients were analyzed, among whom 49 (20.2%) had PIAA. The median postoperative period of PIAA formation was 9 (range: 3-49) days. Among the 49 patients with PIAA, 25 (51.0%) underwent percutaneous ultrasound, computed tomography, or endoscopic ultrasound-guided interventions for PIAA. In the univariate analysis, preoperative indices representing abdominal fat mass (i.e., body mass index, subcutaneous fat area, and visceral fat area) were identified as predictive factors for PIAA; in the multivariate analysis, C-reactive protein (CRP) level (continuous variable) on postoperative day (POD) 3 (odds ratio: 1.189, 95.0% confidence interval: 1.111 - 1.274; P < 0.001) was the only independent and significant predictive factor for PIAA. CONCLUSIONS: CRP level on POD 3 was an independent and significant predictive factor for PIAA after distal pancreatectomy.

Genomic analysis of familial pancreatic cancers and intraductal papillary mucinous neoplasms: A cross-sectional study.

Environmental and genetic factors play a critical role in the pathogenesis of pancreatic cancer, which is likely to follow a multistep process that includes intraductal papillary mucinous neoplasm. The pathogenesis of familial pancreatic cancer has been reported; however, epidemiological characteristics and causative genes remain unclear. This study aimed to determine the relationship between the family history of pancreatic cancer and tumor malignancy and identify novel susceptible germline variants of pancreatic cancer. We performed an epidemiologic study at our institute on a cohort of 668 patients with intraductal papillary mucinous neoplasm and 242 with pancreatic cancer but without associated intraductal papillary mucinous neoplasm stratified by family history of pancreatic cancer. Whole-exome sequencing was conducted for 10 patients from seven families with familial pancreatic cancer and intraductal papillary mucinous neoplasm. We found that patients who had intraductal papillary mucinous neoplasm with positive family history of pancreatic cancer within first-degree relatives were more likely to develop malignancy in a shorter period than those without family history. Duplicate frameshift variants in TET2 c.3180dupG (p.Pro1061fs) and ASXL1 c.1934dupG (p.Gly646fs) in one family and POLN c.1194dupT (p.Glu399fs) in another were identified as pathogenic truncating germline variants which were previously recognised susceptibility genes. Moreover, PDIA2 c.1403C>T (p.Pro468Leu) and DPYSL4 c.926C>A (p.Pro309Gln) were shared in four and two patients, respectively. In particular, PDIA2 was identified as a novel candidate for one of the deleterious variants of familial pancreatic cancer.

Double-multilayer monochromators for high-energy and large-field X-ray imaging applications with intense pink beams at SPring-8 BL20B2.

In this study, double-multilayer monochromators that generate intense, high-energy, pink X-ray beams are designed, installed and evaluated at the SPring-8 medium-length (215 m) bending-magnet beamline BL20B2 for imaging applications. Two pairs of W/B4C multilayer mirrors are designed to utilize photon energies of 110 keV and 40 keV with bandwidths of 0.8% and 4.8%, respectively, which are more than 100 times larger when compared with the Si double-crystal monochromator (DCM) with a bandwidth of less than 0.01%. At an experimental hutch located 210 m away from the source, a large and uniform beam of size 14 mm (V) × 300 mm (H) [21 mm (V) × 300 mm (H)] was generated with a high flux density of 1.6 × 109 photons s-1 mm-2 (6.9 × 1010 photons s-1 mm-2) at 110 keV (40 keV), which marked a 300 (190) times increase in the photon flux when compared with a DCM with Si 511 (111) diffraction. The intense pink beams facilitate advanced X-ray imaging for large-sized objects such as fossils, rocks, organs and electronic devices with high speed and high spatial resolution.

Proteomic and phospholipidomic characterization of extracellular vesicles inducing tumor microenvironment in Epstein-Barr virus-associated lymphomas.

Epstein-Barr virus (EBV) causes malignant carcinomas including B cell lymphomas accompanied by the systemic inflammation. Previously, we observed that phosphatidylserine (PS)-exposing subset of extracellular vesicles (EVs) secreted from an EBV strain Akata-transformed lymphoma (Akata EVs) convert surrounding phagocytes into tumor-associated macrophages (TAMs) via induction of inflammatory response, which is in part mediated by EBV-derived micro RNAs. However, it is still unclear about EV-carried other potential inflammatory factors associated with TAM formation in EBV lymphomas. To this end, we sought to explore proteomic and phospholipidomic profiles of PS-exposing EVs derived from EBV-transformed lymphomas. Mass spectrometric analysis revealed that several immunomodulatory proteins including integrin αLß2 and fibroblast growth factor 2 (FGF2) were highly expressed in PS-exposing Akata EVs compared with another EBV strain B95-8-transformed lymphoma-derived counterparts which significantly lack TAM-inducing ability. Pharmacological inhibition of either integrin αLß2 or FGF2 hampered cytokine induction in monocytic cultured cells elicited by PS-exposing Akata EVs, suggesting the involvement of these proteins in EV-mediated TAM induction in EBV lymphomas. In addition, phospholipids containing precursors of immunomodulatory lipid mediators were also enriched in PS-exposing Akata EVs compared with B95-8 counterparts. Phospholipidomic analysis of fractionated Akata EVs by density gradient centrifugation further demonstrated that PS-exposing Akata EVs might be identical to certain Akata EVs in low density fractions containing exosomes. Therefore, we concluded that a variety of immunomodulatory cargo molecules in a certain EV subtype are presumably conducive to the development of EBV lymphomas.

Time course of capillary regression and an expression balance between vascular endothelial growth factor-A and thrombospondin-1 in the soleus muscle of hindlimb unloaded rats.

INTRODUCTION/AIMS: Skeletal muscle capillaries regress with disuse; however, information on time-dependent changes in the expression of pro- and anti-angiogenic factors in disused muscle is limited. This study aimed to clarify time-dependent changes in skeletal muscle capillarization, pro-angiogenic vascular endothelial growth factor-A (VEGF-A), and anti-angiogenic thrombospondin-1 (TSP-1) in the soleus muscle of hindlimb unloaded rat. METHODS: Eight-week-old male Sprague Dawley rats were randomly divided into four groups corresponding to different hindlimb unloading (HU) duration at 0, 1, 2, and 3 wk. RESULTS: Muscle atrophy and capillary regression worsened in the soleus muscle with longer periods of HU. The VEGF-A protein expression level was lower at week 1 than at week 0. In addition, the value at week 3 was also lower than those at weeks 0, 1, and 2. The TSP-1 protein expression level was higher at week 1 than that at week 0 but was similar at weeks 2 and 3. Moreover, reactive oxygen species, assessed by dihydroethidium fluorescence intensity on cryosection, were higher at weeks 2 and 3 than that at week 0. DISCUSSION: Depending on the HU period, VEGF-A and TSP-1 showed different expression patterns. In the early HU phase, TSP-1 may play an important role in capillary regression. However, when HU extends for a longer period, decreased VEGF-A, and/or increased oxidative stress may be more involved in capillary regression.

Reappraisal of liver transplantation for erythropoietic protoporphyria: A deadly combination of disease recurrence and biliary complication.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare inherited disorder that causes the accumulation of protoporphyrin in the erythrocytes, skin, and liver. Severe protoporphyric hepatopathy results in liver failure, requiring both liver and bone marrow transplantation as a life-saving procedure and to correct the underlying enzymatic defect, respectively. CASE PRESENTATION: We report a 20-year-old man who underwent split liver transplantation using a right trisegment and caudate lobe graft for EPP-induced liver failure, but succumbed to a deadly combination of early relapse of EPP and subsequent, intractable, late-onset bile leakage from the cut surface of segment 4. EPP recurrence most likely created a high-risk situation for bile leakage from the non-communicating bile ducts of segment 4; therefore, this case shed light on the potential relationship between EPP recurrence and biliary complications. CONCLUSION: Physicians should recognize the potentially rapid and life-threatening progression of protoporphyric hepatopathy that leads to liver failure. For young patients with EPP, LT and sequential BMT should thoroughly be considered by a multidisciplinary team as soon as hepatic reserve deterioration becomes evident. Split liver transplantation should preferably be avoided and appropriate post-transplant management is critical before protoporphyrin depositions to the bile duct and hepatocyte causes irreversible damage to the liver graft.

Measuring the quality of life of long-term care service users in Japan: a cross-sectional questionnaire study.

BACKGROUND: In Japan's super-aging society, the number of long-term care service providers is increasing, and the quality of care is a matter of concern. One aspect of the quality of care is the user's quality of life. The questionnaires EQ-5D and WHO-5 are representative indicators of quality of life. Herein, we aimed to measure the quality of life in long-term care service users in Japan and to clarify the relationship between quality of life and the level of care required. METHODS: A questionnaire study was conducted in 106 facilities of 22 corporations. In addition to the EQ-5D and WHO-5, sex, age, and the level of care required were assessed by descriptive statistics. Bonferroni's multiple comparison test was used to analyze each quality of life score, and the differences by sex and age were analyzed multiple regression analyses, with each quality of life score as the objective variable. RESULTS: Of 4647 cases collected, 2830 were analyzed, with no missing data. Both indicators tended to be lower than the general older population. Those scores tended to be higher in females than males (EQ-5D: males, 0.58 ± 0.26; females, 0.60 ± 0.24; P = 0.06 and WHO-5: males, 13.8 ± 5.92; females 14.9 ± 5.70; P < 0.001). In terms of age, those under 65 years old with specific diseases had lower EQ-5D scores than those in other age groups (P < 0.001); however, WHO-5 scores did not differ by age. Multiple regression analysis showed a significant association between the EQ-5D score and level of care required, except for support-required level 1, which tended to worsen as the level of care required increased. Conversely, the WHO-5 score was significantly lower for care need levels 2, 4, and 5. CONCLUSIONS: The quality of life of long-term care service users was worse than that of the general older population, it tended to be low among males and those under 65 years old with specific diseases. Furthermore, it gradually decreased as the level of care required increased. It is important to monitor users' quality of life as a quality indicator of care, to improve and manage it.

Reconsideration of operative indications in pancreatic neuroendocrine neoplasms.

BACKGROUND: The incidence of pancreatic neuroendocrine neoplasm (PNEN) has been increasing. Resection is typically indicated for PNEN, regardless of its size; however, the indications for its resection are controversial. This study aimed to evaluate the treatment results of surgical resection of PNEN at our institute. METHODS: In this single-center, retrospective, case-control study, 87 patients who underwent PNEN resection and 17 patients with PNEN who did not undergo surgical resection between 1993 and 2020 were included in this study. Clinical characteristics and outcomes were reviewed and statistically compared. Survival was also estimated for the patients in each cohort. RESULTS: Seventeen patients who underwent resection (20%) had lymph node metastasis. Tumors measuring ≥ 2.0 cm and multiple lesions were identified as independent predictors for lymph node metastasis (odds ratio [OR] 17.3, 95% confidence interval [CI] 3.0-100.0, p = 0.001 and OR 8.7, 95% CI 1.5-52.0, p = 0.018, respectively). There was a significant difference in the survival curves depending on the presence or absence of lymph node metastasis (5-year overall survival 74.7% vs. 94.3%, p < 0.001; 5-year recurrence-free survival: 66.3% vs. 93.6%, p < 0.001). All 17 PNEN cases under observation with a median 8 mm (range 5-23) tumor size for a median of 34 (range 2.4-114) months showed slight morphological change with a median tumor growth rate of 0.15 mm (range 0-3.33) per year. CONCLUSION: Patients with tumors measuring ≥ 2.0 cm have a high probability of lymph node metastasis or recurrence, thereby requiring resection. PNEN measuring < 1.0 cm may be acceptable for observation.

Systematic Review and Metaanalysis of Lymph Node Metastases of Resected Pancreatic Neuroendocrine Tumors.

BACKGROUND: The optimal surgical strategy for pancreatic neuroendocrine tumors (PNETs) is unknown. However, current guidelines recommend a watch-and-wait strategy for small nonfunctional PNETs (NF-PNETs). The aim of this study is to investigate the risk stratification and prognostic significance of lymph node metastasis (LNM) of PNETs to guide decision-making for lymphadenectomy. PATIENTS AND METHODS: The MEDLINE and Web of Science databases were systematically searched for studies reporting either risk factors of LNM in resected PNETs or survival of patients with LNM. The weighted average incidence of LNM was calculated according to tumor characteristics. Random-effects metaanalyses were performed, and pooled hazard ratios (HR) and their 95% confidence intervals (CI) were calculated to determine the impact of LNM on overall survival (OS). In subgroup analyses, NF-PNETs were assessed. RESULTS: From a total of 5883 articles, 98 retrospective studies with 13,374 patients undergoing resection for PNET were included. In all PNETs, the weighted median rates of LNM were 11.5% for small (≤ 2 cm) PNETs and 15.8% for G1 PNETs. In NF-PNETs, the rates were 11.2% for small PNETs and 10.3% for G1 PNETs. LNM of all PNETs (HR 3.87, 95% CI 3.00-4.99, P < 0.001) and NF-PNETs (HR 4.98, 95% CI 2.81-8.83, P < 0.001) was associated with worse OS. CONCLUSIONS: LNM is potentially prevalent even in small and well-differentiated PNETs and is associated with worse prognosis. A watch-and-wait strategy for small NF-PNETs should be reappraised, and oncologic resection with lymphadenectomy can be considered. Prospective and controlled studies are needed in the future.

Hybrid polarization grating for mode detection of vector beams.

A hybrid polarization grating that can spatially separate orthogonal states of a vector beam with the same polarization topological charge is presented. The hybrid polarization grating is assembled using a fork-shaped polarization grating and a quarter-wave polarization grating and acts as a common pass interferometer for right- and left-circular polarization components of incident vector beams. The hybrid polarization grating can separate two vector beam states that have a 90 ° relative polarization azimuth angle difference. The number of detectable vector beams can be increased by replacing the hybrid polarization grating with a crossed-hybrid polarization grating. Device feasibility was demonstrated experimentally using hybrid polarization grating and crossed-hybrid polarization grating fabricated using the photoalignment method for photoreactive liquid crystals. This approach has the potential to demultiplex several vector beams stably and simultaneously using a compact optical system and should be applicable to vector beam division multiplexing and other applications requiring vector beam detection.