Effect of bone density on the drill-hole diameter made by a cannulated drill bit in cancellous bone.

BACKGROUND: When a pilot hole is made prior to a screw's insertion into bone, the same drill bit is used irrespective of the bone quality. However, osteoporotic bone is fragile and this may affect the hole diameter, which is of particular concern in cancellous bone. In this study, the relationship between bone density and drill-hole diameter was investigated assuming a pre-drilling process in screw-only osteosynthesis in the metaphysis and epiphysis. METHODS: Two types of drill bit (triple-flute [T] and quadruple-flute [Q]) with different shapes and diameters were prepared: type T bits with 3.5 mm and 4.4 mm diameters, and type Q bits with 3.5 mm and 4.2 mm diameters. Drilling was performed manually in simulated bones with four densities: 5, 10, 15, and 20 pounds per cubic foot. We measured the hole diameters with a coordinate measuring machine and analyzed the relationship between the drill-hole diameters and the densities of the simulated bones. We then compared the screw pull-out strength between the two 3.5-diameter drill bits. RESULTS: In all cases, the diameters of the drill holes were larger than those of the drill bits. The relationship between the drill-hole diameters and the bone densities was a negative linear correlation. Enlarging the hole diameter decreased the screw pull-out strength. CONCLUSIONS: For cannulated drill bits of 3.5, 4.2 and 4.4 mm diameter, the diameter of the drill hole in cancellous bone obtained by the manual drilling technique tends to be larger in low-density (e.g., osteoporotic) compared to high-density (e.g., healthy) bone.

Relationship between thread depth and fixation strength in cancellous bone screw.

BACKGROUND: Clarifying the effect of each parameter of screw design on its fixation strength is critical in the development of any type of screw. The purpose of this study was to clarify the relationship between the thread depth and fixation strength of metal screws for cancellous bone. METHODS: Nine types of custom-made screws with the only changed variable being the thread depth were manufactured. Other elements were fixed at a major diameter of 4.5 mm, a thread region length of 15 mm, a pitch of 1.6 mm, and a thread width of 0.20 mm. The pull-out strength and insertion torque of each screw were measured for each of two foam-block densities (10 or 20 pcf). The correlation between the thread depth of the screw and the mechanical findings were investigated with single regression analysis. RESULTS: Regardless of the foam-block density, the pull-out strength significantly increased as the thread depth increased from 0.1 mm to 0.4 mm; after that, the increase was more gradual (p < 0.01, respectively). The relationship between the thread depth and insertion torque was similar. In addition, the insertion torque tended to be more strongly affected by screw depth than the pull-out strength (2.6 times at 20 pcf and 1.4 times at 10 pcf). CONCLUSIONS: The pull-out strength of 4.5-mm-diameter metal screws in a cancellous bone model was found to be biphasic, although linearly correlated with the change in screw depth in both phases. The boundary of the correlation was 0.4 mm regardless of the density of the bone model, with the effect of screw depth on pull-out strength beyond that being small in comparison.

Association of pediatric inguinal hernia contents with patient age and sex.

BACKGROUND: Although pediatric inguinal hernia (IH) is a very common disease, systematic reviews of herniated organs are scarce. The current study aims to clarify the contents of pediatric IH using preoperative ultrasonography (US) in association with patient age, sex, and risk for developing irreducible/strangulated hernia. METHODS: The medical records of pediatric IH patients who underwent inguinal US examination prior to surgery between 2014 and 2019 were reviewed. Hernia contents were categorized into four groups based on US findings: bowel, omentum, ovary with or without fallopian tube, and ascites. RESULTS: A total of 524 IH lesions found in 220 men and 304 women were analyzed. The most common hernia content in patients under 12 months of age was the bowel (91.0%) in males and ovaries (89.5%) in females. The omentum became the most common herniated organ in both men (78.6%) and women (88.0%) aged 2 years and older. Emergency operations were performed in 3 patients (0.57%) due to irreducible IH, where 2 patients with irreducible ovaries, 5 and 7 months old, developed ovarian torsion and needed to undergo emergent salpingo-oophorectomy. CONCLUSIONS: The contents of pediatric IH depended on patient age and sex. Herniated ovaries in infants can twist in the hernia sac and become strangulated. It is important for clinicians to expect the herniated organ and take appropriate measures in the pediatric primary care setting.

Transdermal entry of yeast components elicits transient B cell-associated responses in skin-draining lymph nodes.

Immune responses to non-pathogenic yeasts induced within the draining lymph node remain to be understood. In this study, we have investigated the changes in lymphocytes and their activity in skin-draining lymph nodes in response to transdermally injected zymosan (component of the yeast cell wall). Zymosan elicited the transient increase of B cell number and activation status without affecting the capacity for proliferation. The increased B cell content in the regional lymph nodes was likely due to the reduction of B cell egress from the tissue and in part the increase of homing from the circulation. Zymosan also upregulated the inflammatory cytokines, such as IL-1ß, IL-6, IL-12, and IFNγ, regulatory cytokines IL-10 and TGFß, and lymphoid chemokine CXCL13. Among these, the expression of IL-12 and IL-10 was markedly high in B cells. Altogether, these findings demonstrate a unique B cell-associated response to non-pathogenic yeast component in the draining lymph nodes. This will provide insights into the clinical and healthcare applications of non-pathogenic beneficial microbes.

Visualizing the Rapid and Dynamic Elimination of Allogeneic T Cells in Secondary Lymphoid Organs.

Allogeneic organ transplants are rejected by the recipient immune system within several days or weeks. However, the rejection process of allogeneic T (allo-T) cells is poorly understood. In this study, using fluorescence-based monitoring and two-photon live imaging in mouse adoptive transfer system, we visualized the fate of allo-T cells in the in vivo environment and showed rapid elimination in secondary lymphoid organs (SLOs). Although i.v. transferred allo-T cells efficiently entered host SLOs, including lymph nodes and the spleen, ∼70% of the cells had disappeared within 24 h. At early time points, allo-T cells robustly migrated in the T cell area, whereas after 8 h, the numbers of arrested cells and cell fragments were dramatically elevated. Apoptotic breakdown of allo-T cells released a large amount of cell debris, which was efficiently phagocytosed and cleared by CD8+ dendritic cells. Rapid elimination of allo-T cells was also observed in nu/nu recipients. Depletion of NK cells abrogated allo-T cell reduction only in a specific combination of donor and recipient genetic backgrounds. In addition, F1 hybrid transfer experiments showed that allo-T cell killing was independent of the missing-self signature typically recognized by NK cells. These suggest the presence of a unique and previously uncharacterized modality of allorecognition by the host immune system. Taken together, our findings reveal an extremely efficient and dynamic process of allogeneic lymphocyte elimination in SLOs, which could not be recapitulated in vitro and is distinct from the rejection of solid organ and bone marrow transplants.

Comparison of lymphatic complications between sentinel node navigation surgery and pelvic lymphadenectomy in patients with cervical cancer.

BACKGROUND: Sentinel node navigation surgery (SNNS) has been frequently used in early cervical cancer. However, the incidence and potential reduction of lymphatic complications following the removal of the sentinel lymph node remain unknown. Thus, this study aimed to evaluate the occurrence of lymphatic complications post sentinel node navigation surgery in patients with early cervical cancer. METHODS: A total of 167 patients, including 70 and 97 patients who had undergone SNNS and pelvic lymphadenectomy (PLA), respectively, were enrolled in this study. We compared the lymphatic complications (lower extremity lymphedema and pelvic lymphocele) between the SNNS and PLA groups. RESULTS: The median number of sentinel lymph nodes removed was 2 (range: 1-14). Among the 70 patients in the SNNS group, there were 0 (0%) and 3 (4.3%) occurrences of lower extremity lymphedema and pelvic lymphocele, respectively. The occurrences of lower extremity lymphedema and pelvic lymphocele were significantly lower in the SNNS group than in the PLA group, despite circumflex iliac node removal. CONCLUSIONS: The occurrence of lymphatic complications (lower extremity lymphedema and pelvic lymphocele) was significantly lower in the SNNS group than in the PLA group. We found that SNNS, and not PLA, was the best treatment option for preventing the development of lower extremity lymphedema and pelvic lymphocele, despite circumflex iliac node preservation.

Comparison of survival outcomes between laparoscopic and open surgery in patients with low-risk endometrial cancer.

OBJECTIVE: To evaluate the feasibility, safety and surgical outcomes of laparoscopic surgery for the treatment of low-risk endometrial cancer. METHODS: Of 155 patients with low-risk endometrial cancer, who were included in this retrospective study between May 2008 and March 2017, 82 and 73 underwent laparoscopic and open surgery, respectively. Clinicopathological and surgical data, recurrence-free survival and overall survival were analyzed. RESULTS: No statistically significant differences in median age, final pathological type, International Federation of Gynecology and Obstetrics stage and lymphovascular space involvement were observed between the laparoscopic and open surgery groups. No procedure in the laparoscopic surgery group was converted to open surgery. The median follow-up period was 60 months, with oncologic recurrence identified in three cases (one lung carcinoma and two pelvic cavity carcinomas) in the laparoscopic surgery group. There was no significant between-group difference in 5-year recurrence-free survival (laparoscopic surgery group: 96.3%, open surgery group: 92.6%) and overall survival (laparoscopic surgery group: 100%, open surgery group: 95.4%). CONCLUSIONS: Laparoscopic surgery is a feasible and safe treatment for endometrial cancer and should be considered as a standard treatment option for low-risk endometrial cancer.

Comparison of lymphoscintigraphy and single photon emission computed tomography with computed tomography (SPECT/CT) for sentinel lymph node detection in endometrial cancer.

BACKGROUND: Endometrial cancer is the most common gynecologic cancer, and lymph node metastasis is one of the most important prognostic factors. Increasing evidence shows that sentinel lymph node (SLN) mapping is an effective alternative to comprehensive lymphadenectomy. Single photon emission CT with computed tomography (SPECT/CT) is associated with a high SLN detection rate. OBJECTIVE: To compare the clinical efficacy of SPECT/CT with that of lymphoscintigraphy in detecting SLNs in patients with endometrial cancer. METHODS: Between May 2014 and October 2018, 151 patients with endometrial cancer were enrolled in this study at the Department of Obstetrics and Gynecology of the Kagoshima University Hospital. Inclusion criteria were patients with endometrial cancer, older than 18 years, and with pre-operative International Federation of Gynecology and Obstetrics (FIGO) staging of I and II. All patients underwent pre-operative CT, and patients with suspected peritoneal dissemination and lymph node metastasis were excluded from this study. Pelvic SLNs were detected by injection of tecnetium-99m-labeled phytate into the uterine cervix. The number and locations of SLNs detected using lymphoscintigraphy and SPECT/CT were evaluated. JMP software (version 14, SAS Institute Inc., Cary, North Carolina, USA) was used for statistical analysis. RESULTS: A total of 151 patients who underwent pre-operative lymphoscintigraphy and SPECT/CT were included in the study. The median age was 57 years (range 24-79), and the median body mass index was 24.3 kg/m2 (range 16-40). The final pathology was as follows: 135 (89%) endometrioid carcinoma, 11 (7%) serous carcinoma, one (1%) clear cell carcinoma, and four (3%) other histotypes. Based on SPECT/CT, 204 pelvic SLNs were detected. The bilateral pelvic SLN detection rate was better for SPECT/CT (43% (65/151)) than for lymphoscintigraphy (32% (48/151)) (p<0.0001). The overall pelvic SLN detection rate (at least one pelvic SLN detected) was also better with SPECT/CT (77% (16/151)) vs lymphoscintigraphy (68% (102/151)) (p<0.0001). The distribution of SLN locations detected using SPECT/CT was as follows: external iliac, 91 (45%); obturator, 61 (30%); common iliac, 28 (14%); internal iliac, 19 (9%); para-aortic, 2 (1%); parametrium, 2 (1%), and presacral, 1 (1%). The SLN detection rate using SPECT/CT was significantly worse in patients of advanced age (p<0.0001). DISCUSSION: Overall and bilateral SLN detection rate was better with SPECT/CT than with lymphoscintigraphy in patients with stage I/II endometrial cancer.

Quantitative RT-PCR Assay for Detecting Lymph Node Metastasis in Endometrial Cancer: A Preliminary Study.

OBJECTIVE: The detection accuracy of sentinel lymph node (SLN) metastasis by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) for endometrial cancer (EC) remains unclear and was assessed in this preliminary study. METHODS: We studied primary cancer tissues and pelvic lymph nodes (PLN) from 105 patients with EC. qRT-PCR assay was performed to determine the copy numbers of CK19 mRNA in EC tissues, and negative and positive LN samples. Further, qRT-PCR results were compared with pathological findings. RESULTS: CK19 mRNA expression was detected in 98% (104/106) of the tumors, with a median copy number of 3.0 × 105/µL. Twelve LN were diagnosed as positive by pathological examination. The median copy number of CK19 mRNA for positive and negative LN was 8.1 × 104/µL and 90.4/µL, respectively. CK19 mRNA expression was higher in pathologically positive LN than in pathologically negative LN (p < 0.01); the pathological and qRT-PCR findings showed no discrepancy. When the cutoff value was set at 4,500 copies/µL, qRT-PCR assay using CK19 mRNA exhibited high sensitivity and specificity. CONCLUSIONS: Our results demonstrated that qRT-PCR assay, using CK19 mRNA, exhibits a high accuracy for detecting LN metastasis in EC and represents a useful alternative to conventional pathological diagnosis of EC.

Learning curve and surgical outcomes for laparoscopic surgery, including pelvic lymphadenectomy, for early stage endometrial cancer.

BACKGROUND: The purpose of this study was to determine the learning curve of laparoscopic surgery for the treatment of early endometrial cancer and report the surgical outcomes. METHODS: Patients: Data were retrospectively extracted from the medical charts of patients who underwent laparoscopic surgery. INTERVENTION: Laparoscopic surgery, including pelvic lymphadenectomy, was performed using the same technique and instruments for all patients. OUTCOMES: The learning curve for the surgical technique, characterized by the operative time, number of lymph nodes removed, and volume of intra-operative blood loss, was analyzed. RESULTS: Over the period of observation, 82 patients were enrolled. For analysis, cases were classified into four groups, based on their surgery date. Between-group comparisons identified a significant decrease in operative time and volume of blood loss between Groups 1 and 4 (P < 0.05). However, the number of lymph nodes removed, and the length of hospital stay were not influenced by learning. CONCLUSION: The operative time and the amount of blood loss significantly decreased with an increase in the surgeon's experience but with no effect of learning on the number of lymph nodes removed and length of hospital stay.

Extensively re-organized systemic lymph nodes provide a feasible environment for self-reactivity in lupus-prone NZB × NZW F1 mice.

Lymphadenopathy is a frequently observed symptom in systemic lupus erythematosus, although the immunological role of lymph nodes (LNs) in systemic autoimmunity remains largely unknown. Here, we performed comprehensive and systematic analyses of LNs in lupus-prone NZB × NZW F1 (BWF1) mice, demonstrating extensive tissue re-organization of the systemic LNs with follicular expansion, hyper germinal center (GC) formation, atrophy of the paracortical T-cell area and expansion of the medulla in aged BWF1 mice bearing glomerulonephritis. The proportion of B cells was significantly increased in these reactive LNs but not in the spleen, and lymphocyte subsets involved in antibody production, i.e. GC B cells, follicular helper T cells and plasma cells, were elevated. Draining LNs of the affected organs, such as the renal and cervical nodes, showed enhanced tissue re-organization and accumulation of effector lymphocytes, suggesting the presence of a positive feedback loop of regional responses. LN cells isolated from disease-bearing animals produced anti-DNA antibody, indicating activation of autoreactive lymphocytes in situ. The substantial development of disease and LN alterations in mice that received a splenectomy at a young age points to the importance of other secondary lymphoid organs, most likely LNs, for the progression of autoimmune responses independent of the spleen. Taken together, our findings highlight the value of taking LN alterations and activities into consideration for understanding the pathogenesis of systemic autoimmunity.

Risk factors for lymphatic complications following lymphadenectomy in patients with cervical cancer.

BACKGROUND: The purpose of this study was to evaluate the occurrence of lymphatic complications following pelvic lymphadenectomy (PLA) in patients with cervical cancer. METHODS: A retrospective study of 169 cervical cancer patients was conducted. Lower extremity lymphedema (LEL) was diagnosed using the International Society of Lymphology guidelines, and pelvic lymphocele (PL) was evaluated using trans-vaginal ultrasonography and computed tomography. RESULTS: The median patient age was 46 years (range: 22-74) and median body mass index was 21.7 kg/m2 (range: 15.7-37.1). The median number of lymph nodes (LNs) removed was 27 (range: 22-74); 94 (55.6%) patients underwent circumflex iliac node (CIN) dissection; 39 (23.1%) patients received adjuvant chemotherapy; and 81 (47.9%) patients received adjuvant postoperative radiotherapy. There were 28 (16.6%) and 32 (18.9%) occurrences of LEL and PL, respectively. In multivariate logistic regression analysis, the number of LNs removed (odds ratio [OR]: 3.37; 95% CI: 1.43-8.54; P = 0.0053) and CIN removal (OR: 3.92; 95% CI: 1.55-11.4; P = 0.0033) were independent risk factors for LEL; however, no risk factors were significantly associated with PL. CONCLUSIONS: Our results demonstrated that CIN removal and the number of LNs removed were significant risk factors for LEL in patients with cervical cancer. However, we did not identify any significant risk factors for PL in this study. We instead speculate that LN dissection itself causes PL. We suggest that establishment of comprehensive PLA without CIN dissection, or use of the sentinel lymph node concept, will prevent the occurrence of lymphatic complications in cervical cancer patients.

RASAL3, a novel hematopoietic RasGAP protein, regulates the number and functions of NKT cells.

Ras GTPase-activating proteins negatively regulate the Ras/Erk signaling pathway, thereby playing crucial roles in the proliferation, function, and development of various types of cells. In this study, we identified a novel Ras GTPase-activating proteins protein, RASAL3, which is predominantly expressed in cells of hematopoietic lineages, including NKT, B, and T cells. We established systemic RASAL3-deficient mice, and the mice exhibited a severe decrease in NKT cells in the liver at 8 weeks of age. The treatment of RASAL3-deficient mice with α-GalCer, a specific agonist for NKT cells, induced liver damage, but the level was less severe than that in RASAL3-competent mice, and the attenuated liver damage was accompanied by a reduced production of interleukin-4 and interferon-γ from NKT cells. RASAL3-deficient NKT cells treated with α-GalCer in vitro presented augmented Erk phosphorylation, suggesting that there is dysregulated Ras signaling in the NKT cells of RASAL3-deficient mice. Taken together, these results suggest that RASAL3 plays an important role in the expansion and functions of NKT cells in the liver by negatively regulating Ras/Erk signaling, and might be a therapeutic target for NKT-associated diseases.

Reactivity of autoantibodies against not only erythrocytes but also hepatocytes in sera of mice with malaria.

In order to further examine the reactivity of autoantibodies, mice were infected with a non-lethal strain of Plasmodium yoelii. Parasitemia appeared between days 10 and 21. During this period, hyperglycemia and hypothermia were serially obeserved and this phenomenon resembled stress-associated responses. In parallel with parasitemia, autoantibodies appeared against nucleus and double-stranded DNA in the sera. To examine further the reactivity of autoantibodies against tissues, immunohistochemical staining using sera from mice with or without malaria was conducted. Autoantibodies contained reactivity to erythrocytes in the spleen, bone marrow and peripheral blood, especially against tissues obtained from mice with malaria. In the liver and intestine, autoantibodies reacted with hepatocytes and intestinal epithelial cells, respectively. These results suggested that the reactivity of autoantibodies against erythrocytes and hepatocytes might be associated with the modulation of the disease course in malaria.

Extracellular ATP-stimulated macrophages produce macrophage inflammatory protein-2 which is important for neutrophil migration.

Macrophages are the major source of the chemokines macrophage inflammatory protein-2 (MIP-2) and keratinocyte-derived chemokine (KC), which play a major role in neutrophil migration to sites of inflammation. Although extracellular ATP from inflammatory tissues induces several immune responses in macrophages, it is unclear whether ATP-stimulated macrophages affect neutrophil migration. Therefore, the aim of the present study was to investigate the role of ATP-induced MIP-2 production by macrophages. When ATP was injected intraperitoneally into mice, the number of neutrophils within the peritoneal cavity markedly increased, along with the levels of MIP-2 and KC in the peritoneal lavage fluid. Consistent with this, ATP induced MIP-2 production, but not that of KC, by peritoneal exudate macrophages (PEMs) in vitro. This occurred via interactions with the P2X(7) receptor and P2Y(2) receptor. Furthermore, treatment of PEMs with ATP led to the production of reactive oxygen species. The ATP-induced MIP-2 production was inhibited by treatment with the antioxidant N-acetyl-l-cysteine. Also, MIP-2 production was inhibited by pre-incubating PEMs with inhibitors of extracellular signal-regulated kinase 1/2 or p38 mitogen-activated protein kinase. The MIP-2 neutralization reduced the increase in neutrophil numbers observed in ATP-treated mice. Taken together, these results suggest that increased production of reactive oxygen species by ATP-stimulated macrophages activates the signalling pathways that promote MIP-2 production which, in turn, induces neutrophil migration.

Natural killer T cells suppress zymosan A-mediated granuloma formation in the liver by modulating interferon-γ and interleukin-10.

Wild-type (WT) and CD1d(-/-) [without natural killer (NK) T cells] mice were treated with zymosan A to induce granuloma formation in the liver. Increased granuloma formation was seen in NKT-less mice on days 7 and 14 after administration. WT mice showed limited granuloma formation, and zymosan A eventually induced NKT cell accumulation as identified by their surface marker (e.g. CD1d-tetramer). Zymosan A augmented the expression of Toll-like receptor 2 on the cell surface of both macrophages and NKT cells. One possible reason for accelerated granuloma formation in NKT-less mice was increased production of interferon- γ (IFN-γ); a theory that was confirmed using IFN-γ(-/-) mice. Also, zymosan A increased interleukin-10 production in WT mice, which suppresses IFN-γ production. Taken together, these results suggest that NKT cells in the liver have the potential to suppress zymosan A-mediated granuloma formation.

Coincidence of autoantibody production with the activation of natural killer T cells in α-galactosylceramide-mediated hepatic injury.

Natural killer T (NKT) cells are known to be specifically activated by α-galactosylceramide (α-GalCer) via their interaction with CD1d. At that time, NKT cells mediate autoreactivity and eventually induce hepatic injury. As these immune responses resemble acute autoimmune hepatitis, it was examined whether autoantibody production and the activation of autoantibody-producing B-1 cells were accompanied by this phenomenon. Autoantibodies against Hep-2 cells and double-stranded DNA were detected in sera as early as day 3 (showing a peak at day 14) when mice were treated with α-GalCer. On day 3, B220(low) cells appeared in the liver. These B220(low) cells were CD5(-) (i.e. B-1b cells) and CD69(+) (an activation marker). Primarily, such B220(low) cells were present in the peritoneal cavity, but the proportion of B220(low) cells increased with the administration of α-GalCer even at this site. In parallel with the appearance of B220(low) cells in the liver, hepatic lymphocytes acquired the potential to produce autoantibodies in in vitro cell culture in the presence of lipopolysaccharide. These results suggested that hepatic injury induced by α-GalCer administration resembled acute autoimmune hepatitis and that the major effector lymphocytes were NKT cells with autoreactivity and autoantibody-producing B-1 cells.

NKG2A inhibits invariant NKT cell activation in hepatic injury.

Activation of invariant NKT (iNKT) cells in the liver is generally regarded as the critical step for Con A-induced hepatitis, and the role of NK cell receptors for iNKT cell activation is still controversial. In this study we show that blockade of the NKG2A-mediated inhibitory signal with antagonistic anti-NKG2A/C/E mAb (20d5) aggravated Con A-induced hepatitis in wild-type, Fas ligand (FasL)-mutant gld, and IL-4-deficient mice even with NK cell and CD8 T cell depletion, but not in perforin-, IFN-gamma-, or IFN-gamma- and perforin-deficient mice. Consistently, 20d5 pretreatment augmented serum IFN-gamma levels and perforin-dependent cytotoxicity of liver mononuclear cells following Con A injection, but not their FasL/Fas-dependent cytotoxicity. However, blockade of NKG2A-mediated signals during the cytotoxicity effector phase did not augment cytotoxic activity. Activated iNKT cells promptly disappeared after Con A injection, whereas NK1(-) iNKT cells, which preferentially expressed CD94/NKG2A, predominantly remained in the liver. Pretreatment with 20d5 appeared to facilitate disappearance of iNKT cells, particularly NK1(-) iNKT cells. Moreover, Con A-induced and alpha-galactosylceramide-induced hepatic injury was very severe in CD94/NKG2A-deficient DBA/2J mice compared with CD94/NKG2A-intact DBA/2JJcl mice. Overall, these results indicated that a NKG2A-mediated signal negatively regulates iNKT cell activation and hepatic injury.

Patient Safety Activity Under the Social Insurance Medical Fee Schedule in Japan: An Overview of the 2010 Nationwide Survey.

OBJECTIVES: Little is known about patient safety performance under the social insurance medical fee schedule in Japan. The Health Ministry in Japan introduced the preferential patient safety countermeasure fee (PPSCF) to promote patient safety in 2006 and revised the PPSCF system in 2010. This study aims to address the patient safety performance status at hospitals implementing the PPSCF. METHODS: A nationwide questionnaire survey targeting 2674 hospitals with the PPSCF was performed in 2010 to 2011. The 627 participant hospitals were divided into the following three groups: 178 hospitals implementing PPSCF 1 with 400 beds or more (group A), 286 hospitals implementing PPSCF 1 with 399 beds or fewer (group B), and 163 hospitals implementing PPSCF 2 (group C). RESULTS: The mean numbers (standard errors) of patient safety managers were 1.45 (0.07) in group A, 1.12 (0.04) in group B, and 0.37 (0.12) in group C (P < 0.001). The participation number and rates of all staff for the patient safety seminar were 1721 (167) and 1.64 (0.10) in group A, 580 (26) and 1.94 (0.09) in group B, and 349 (31) and 1.98 (0.17) in group C (P < 0.001, P = 0.105).These results can be explained because hospitals with PPSCF 1 (groups A and B) must assign at least one full-time patient safety manager, whereas hospitals with PPSCF 2 (group C) are not required to do so. Patient safety performance at hospitals with PPSCF 1 was more active than that at hospitals with PPSCF 2. However, when the values were converted to per capita or per 100 beds, there were no differences across the three groups. CONCLUSIONS: The PPSCF encourages hospitals to perform actions for patient safety by providing incentives under the social insurance medical fee schedule in Japan.

A Novel Model-Based Questionnaire Based on Low-Dose CT Screening Data for Chronic Obstructive Pulmonary Disease Diagnosis in Shimane, Japan.

Purpose: Although there have been many reports on the use of respiratory function tests and questionnaires for creating chronic obstructive pulmonary disease (COPD) questionnaires, there have been no reports on the effectiveness of questionnaires using computed tomography (CT) screening data. We aimed to validate the International Primary Care Airways Group (IPAG) questionnaire and to propose a novel COPD screening questionnaire based on the CT screening data of Japanese participants. Patients and Methods: Low-dose CT screening was performed for early detection of lung cancer and COPD since 2009 in Shimane, Japan, and clinical information was collected using an original questionnaire that included all the IPAG questionnaire items and eight additional items (for eg, on dyspnea) during CT screening. Participants with emphysema, smoking history, and respiratory symptoms were instructed to undergo a respiratory function test. The participants with the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) <0.7 on the respiratory function test were diagnosed with COPD, and 11,458 participants underwent CT screening from 2013 to 2016 and were enrolled and filtered using <22.5 pack-years. Data from 3252 participants were selected for the final analysis. The receiver operating characteristic curve determined the best cutoff points for discriminating patients with COPD. The efficacy of the questionnaire items was determined using logistic regression analysis. Results: The best cutoff point for the Japanese IPAG questionnaire was 23. The logistic regression analysis revealed significant differences in the question items of "age", "pack-year", "cough", "phlegm", and "feeling of dyspnea". COPD-CT questionnaire was developed based on the CT screening data. The COPD predicted value was determined using the regression model obtained in this study. Conclusion: The IPAG questionnaire had low specificity for discriminating COPD in Japanese patients. A novel questionnaire (COPD-CT) and the COPD predicted value based on the CT screening data was developed.