Multiple site inflammation and acute kidney injury in crush syndrome.

Crush syndrome, which frequently occurs in earthquake disasters, often leads to rhabdomyolysis induced acute kidney injury (RIAKI). Recent findings indicate that systemic inflammatory response syndrome (SIRS) exacerbates muscle collapse, contributing to RIAKI. The purpose of this study is to investigate the involvement of multiple site inflammation, including intraperitoneal, in crush syndrome. In a mouse model of RIAKI, elevated levels of inflammatory mediators such as TNFα, IL-6, myoglobin, and dsDNA were observed in serum and the peritoneal cavity, peaking earlier in the intraperitoneal cavity than in serum or urine. Our previously developed novel peptide inhibiting leukocyte extracellular traps was administered intraperitoneally and blocked all of these mediators in the intraperitoneal cavity and serum, ameliorating muscle damage and consequent RIAKI. Although further studies are needed to determine whether intraperitoneal inflammation associated with muscle collapse can lead to systemic inflammation, resulting in more severe and prolonged muscle damage and renal injury, early suppression of multiple site inflammation, including intraperitoneal, might be an effective therapeutic target.

Simple severity scale for perforated peptic ulcer with generalized peritonitis: A derivation and internal validation study.

BACKGROUND: Perforated peptic ulcer (PPU) causes peritonitis and requires surgery based on disease severity. This study aimed to develop and validate a severity scale for PPU with generalized peritonitis. MATERIALS AND METHODS: This retrospective cohort study used a nationwide multi-center surgical database (2013-2020). Patients aged >15 years who underwent surgery for PPU with generalized peritonitis were included and categorized into the derivation (2013-2018) and two validation (2019 and 2020) cohorts. Possible severity predictors were selected via a literature review, and Lasso models were developed to predict severe postoperative adverse events with 2000 bootstrapping. Final variables for the scoring system were determined based on inclusion frequency (≥90%) in the Lasso models. Discrimination and accuracy were evaluated using c-statistics and calibration plots. Cutoff values for minimal postoperative adverse events were examined using negative predictive values. RESULTS: Among 12,513 patients included (1,202 underwent laparoscopic surgery), 533 (5.9%), 138 (7.6%), and 117 (6.9%) in the derivation and two validation cohorts experienced postoperative adverse events. Age, dyspnea at rest, preoperative sepsis, III/IV/V of American Society of Anesthesiologists physical status, and albumin and creatinine were selected for the final model. A 0-11 scoring system was developed with c-statistics of 0.812-0.819. Cutoff value was determined as 5, which predicted <3% probability of postoperative adverse events regardless of type of surgery. CONCLUSIONS: A score of <5 predicts minimal risks for postoperative adverse events and therefore would be clinically useful to determine type of surgery. Further studies are needed to validate the score.

Urine Output and Development of Acute Kidney Injury in Sepsis: A Multicenter Observational Study.

BACKGROUND: Acute kidney injury (AKI) is common in sepsis and a urine output <0.5 mL/kg/h associated with increased mortality is incorporated into AKI diagnosis. We aimed to identify the urine-output threshold associated with increased AKI incidence and hypothesized that a higher urine output than a specified threshold, which differs from the predominantly used 0.5 mL/kg/h threshold, would be associated with an increased AKI incidence. METHODS: This was a post-hoc analysis of a nationwide prospective observational study. This study included adult patients newly diagnosed with sepsis and requiring intensive care. Urine output on the day of sepsis diagnosis was categorized as low, moderate, or high (<0.5, 0.5-1.0, and >1.0 mL/kg/h, respectively), and we compared AKI incidence, renal replacement therapy (RRT) requirement, and 28-day survival by category. Estimated probabilities for these outcomes were also compared after adjusting for patient background and hourly fluid administration. RESULTS: Among 172 eligible patients, AKI occurred in 46.3%, 48.3%, and 53.1% of those with high, moderate, and low urine output, respectively. The probability of AKI was lower in patients with high urine output than in those with low output (43.6% vs 56.5%; P = .028), whereas RRT requirement was lower in patients with high and moderate urine output (11.7% and 12.8% vs 49.1%; P < .001). Patients with low urine output demonstrated significantly lower survival (87.7% vs 82.8% and 67.8%; P = .018). Cubic spline curves for AKI, RRT, and survival prediction indicated different urine-output thresholds, including <1.2 to 1.3 mL/kg/h for AKI and <0.6 to 0.8 mL/kg/h for RRT and mortality risk. CONCLUSIONS: Urine output >1.0 mL/kg/h on the day of sepsis diagnosis was associated with lower AKI incidence. The urine-output threshold was higher for developing AKI than for RRT requirement or mortality.

Association between Skin Carotenoid Levels and Cognitive Impairment Screened by Mini-Cog in Patients with Glaucoma.

Carotenoids, having strong antioxidant properties, have been associated with neurodegenerative conditions like dementia and glaucoma, characterized by neuronal loss leading to cognitive and visual dysfunction. Therefore, carotenoids have attracted attention as factors predictive of the onset and progression of these neurodegenerative diseases. However, the impact of carotenoids on cognitive impairment and glaucomatous visual field defects remains unexplored. We conducted a retrospective, observational clinical study to investigate the association between skin carotenoid (SC) levels and cognitive impairment, as screened by the Mini-Cog test, in glaucoma patients. The study included 406 participants and 812 eyes were examined (average age: 69.7 ± 11.4 years; 228 men, 178 women) with various types of glaucoma: primary open angle (57.6%), exfoliation (18.6%), and other types (23.8%). SC levels were estimated via pressure-mediated reflection spectroscopy. Mixed-effects regression models were utilized to examine the relationship between SC levels, visual field defects, and Mini-Cog results. Of the participants, 28 (6.9%) tested positive on the Mini-Cog, suggesting cognitive impairment. The average SC level in the Mini-Cog positive group was significantly lower than in the negative group (269.5 ± 86.4 A.U. vs. 329.2 ± 120.4 A.U., respectively; p = 0.01). Additionally, the visual field mean deviation (MD) in the Mini-Cog positive group was notably worse than that in the negative group (-19.64 ± 9.07 dB vs. -12.46 ± 9.28 dB, respectively; p < 0.0001). The mixed-effects regression analysis revealed a significant association between Mini-Cog positivity and lower SC levels (p = 0.0006), although SC levels did not significantly correlate with MD (p = 0.3). Our findings suggest that cognitive impairment in glaucoma patients is associated with lower SC levels, underscoring the potential benefits of maintaining carotenoid levels to slow cognitive function decline. The protective role of carotenoids in glaucoma merits further investigation.

Experience with chemotherapy for postoperative metastases of adenosquamous carcinoma of the esophagogastric junction and pathological study of its development.

We report here a case of postoperative recurrent adenosquamous carcinoma (ASC) of the esophagogastric junction (EGJ) treated with S-1 therapy. A 79-year-old woman was diagnosed with carcinoma of the EGJ. Thoracoscopic subtotal esophagectomy was performed, and pathological examination revealed advanced ASC with lymph node metastasis. Five months after surgery, multiple lung metastases and multiple lymph node metastases were observed, and the patient was treated with S-1 monotherapy, which showed partial response and may be effective for advanced ASC of the EGJ. On the other hand, immunohistological analysis of the tumors showed a relatively wide range of areas that could differentiate into both adenocarcinoma and squamous cell carcinoma, suggesting that tumor cells with multidifferentiation potential, or at least the ability to differentiate into both adeno-epithelial and squamous epithelial cells, were the likely source of the tumors.

Door-to-Needle Time for Extracorporeal Cardiopulmonary Resuscitation and Neurological Outcomes in Out-of-Hospital Cardiac Arrest: A Nationwide Study.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is an option for refractory cardiac arrest, and immediate initiation after indication is recommended. However, the practical goals of ECPR preparation (such as the door-to-needle time) remain unclear. This study aimed to elucidate the association between the door-to-needle time and neurological outcomes of out-of-hospital cardiac arrest. METHODS AND RESULTS: This is a post hoc analysis of a nationwide multicenter study on out-of-hospital cardiac arrest treated with ECPR at 36 institutions between 2013 and 2018 (SAVE-J [Study of Advanced Cardiac Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan] II study). Adult patients without hypothermia (≥32 °C) in whom circulation was not returned at ECPR initiation were included. The probability of favorable neurological function at 30 days (defined as Cerebral Performance Category ≤2) was estimated using a generalized estimating equations model, in which institutional, patient, and treatment characteristics were adjusted. Estimated probabilities were then calculated according to the door-to-needle time with 3-minute increments, and a clinical threshold was assumed. Among 1298 patients eligible for this study, 136 (10.6%) had favorable neurological function. The estimated probability of favorable outcomes was highest in patients with 1 to 3 minutes of door-to-needle time (12.9% [11.4%-14.3%]) and remained at 9% to 10% until 27 to 30 minutes. Then, the probability dropped gradually with each 3-minute delay. A 30-minute threshold was assumed, and shorter door-to-extracorporeal membrane oxygenation/low-flow time and fewer adverse events related to cannulation were observed in patients with door-to-needle time <30 minutes. CONCLUSIONS: The probability of favorable functions after out-of-hospital cardiac arrest decreased as the door-to-needle time for ECPR was prolonged, with a rapid decline after 27 to 30 minutes. REGISTRATION: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000041577; Unique identifier: UMIN000036490.

Novel weaning assessment for veno-arteriovenous to veno-venous extracorporeal membrane oxygenation using pump-controlled retrograde trial off.

INTRODUCTION: Pump-controlled retrograde trial off (PCRTO) is described as an effective weaning strategy for veno-arterial extracorporeal membrane oxygenation (ECMO) in the guidelines. Contrastingly, there is no established weaning strategy for veno-arteriovenous (V-AV) ECMO. We report a novel application of PCRTO in a patient undergoing V-AV ECMO. CASE REPORT: A 49-year-old man had pneumonia and a history of kidney transplantation. Two days after intubation, respiratory failure progressed and veno-venous (V-V) ECMO was introduced. On day 7 after ECMO, the configuration was changed to V-AV ECMO owing to septic cardiomyopathy due to suspected cholangitis. On day 15, with partial haemodynamic improvement and persistent respiratory failure, PCRTO was performed; the patient was safely returned to V-V ECMO. DISCUSSION: In patients undergoing V-AV ECMO, PCRTO could have the potential to accurately simulate decannulation of the arterial cannula. CONCLUSION: This novel weaning strategy could be considered in patients undergoing V-AV ECMO.

Follow-up computed tomography and unexpected hemostasis in non-operative management of pediatric blunt liver and spleen injury.

PURPOSE: While follow-up CT and prophylactic embolization with angiography are often conducted during non-operative management (NOM) for BLSI, particularly in a high-grade injury, the utility of early repeated CT for preventing unexpected hemorrhage remains unclear. This study aimed to elucidate whether early follow-up computerized tomography (CT) within 7 days after admission would decrease unexpected hemostatic procedures on pediatric blunt liver and spleen injury (BLSI). METHODS: A post-hoc analysis of a multicenter observational cohort study on pediatric patients with BLSI (2008-2019) was conducted on those who underwent NOM, in whom the timing of follow-up CT were decided by treating physicians. The incidence of unexpected hemostatic procedure (laparotomy and/or emergency angiography for ruptured pseudoaneurysm) and complications related to BLSI were compared between patients with and without early follow-up CT within 7 days. Inverse probability weighting with propensity scores adjusted patient demographics, comorbidities, mechanism and severity of injury, initial resuscitation, and institutional characteristics. RESULTS: Among 1320 included patients, 552 underwent early follow-up CT. Approximately 25% of patients underwent angiography on the day of admission. The incidence of unexpected hemostasis was similar between patients with and without early repeat CT (8 [1.4%] vs. 6 [0.8%]; adjusted OR, 1.44 [0.62-3.34]; p = 0.40). Patients with repeat CT scans more frequently underwent multiple angiographies (OR, 2.79 [1.32-5.88]) and had more complications related to BLSI, particularly bile leak (OR, 1.73 [1.04-2.87]). CONCLUSION: Follow-up CT scans within 7 days was not associated with reduced unexpected hemostasis in NOM for pediatric BLSI.

Effect of Heparan Sulfate on Vasculogenesis and Dentinogenesis of Dental Pulp Stem Cells.

INTRODUCTION: Heparan sulfate (HS) is a major component of dental pulp tissue. We previously reported that inhibiting HS biosynthesis impedes endothelial differentiation of dental pulp stem cells (DPSCs). However, the underlying mechanisms by which exogenous HS induces DPSC differentiation and pulp tissue regeneration remain unknown. This study explores the impact of exogenous HS on vasculogenesis and dentinogenesis of DPSCs both in vitro and in vivo. METHODS: Human-derived DPSCs were cultured in endothelial and odontogenic differentiation media and treated with HS. Endothelial differentiation of DPSCs was investigated by real-time polymerase chain reaction and capillary sprouting assay. Odontogenic differentiation was assessed through real-time polymerase chain reaction and detection of mineralized dentin-like deposition. Additionally, the influence of HS on pulp tissue was assessed with a direct pulp capping model, in which HS was delivered to exposed pulp tissue in rats. Gelatin sponges were loaded with either phosphate-buffered saline or 101-102 µg/mL HS and placed onto the pulp tissue. Following a 28-day period, tissues were investigated by histological analysis and micro-computed tomography imaging. RESULTS: HS treatment markedly increased expression levels of key endothelial and odontogenic genes, enhanced the formation of capillary-like structures, and promoted the deposition of mineralized matrices. Treatment of exposed pulp tissue with HS in the in vivo pulp capping study induced formation of capillaries and reparative dentin. CONCLUSIONS: Exogenous HS effectively promoted vasculogenesis and dentinogenesis of DPSCs in vitro and induced reparative dentin formation in vivo, highlighting its therapeutic potential for pulp capping treatment.

Association between preoperative lactate level and early complications after surgery for isolated extremity fracture.

BACKGROUND: The role of lactate level in selecting the timing of definitive surgery for isolated extremity fracture remains unclear. Therefore, we aimed to elucidate the use of preoperative lactate level for predicting early postoperative complications. METHODS: This was a single-center retrospective observational study of patients with isolated extremity fracture who underwent orthopedic surgery. Patients who underwent lactate level assessment within 24 h prior to surgery were included. The incidence of early postoperative complications was compared between patients with a preoperative lactate level of ≥ 2 and < 2 mmol/L. Moreover, subgroup analyses were performed based on the time from hospital arrival to surgery and fracture type. RESULTS: In total, 187 patients were included in the study. The incidence of postoperative complications was significantly higher in patients with a preoperative lactate level of ≥ 2 mmol/L than those with a preoperative lactate level of < 2 mmol/L. This result did not change after adjusting for age and severity. Further, a high preoperative lactate level was associated with a greater incidence of postoperative complications in patients who underwent definitive surgery within 6 h after arrival. CONCLUSION: A preoperative lactate level of ≥ 2 mmol/L was associated with a greater incidence of early postoperative complications in isolated extremity fractures. Nevertheless, this correlation was only observed among patients who underwent definitive fixation within 6 h after hospital arrival.

The significant role of glycosaminoglycans in tooth development.

This review delves into the roles of glycosaminoglycans (GAGs), integral components of proteoglycans, in tooth development. Proteoglycans consist of a core protein linked to GAG chains, comprised of repeating disaccharide units. GAGs are classified into several types, such as hyaluronic acid, heparan sulfate, chondroitin sulfate, dermatan sulfate, and keratan sulfate. Functioning as critical macromolecular components within the dental basement membrane, these GAGs facilitate cell adhesion and aggregation, and play key roles in regulating cell proliferation and differentiation, thereby significantly influencing tooth morphogenesis. Notably, our recent research has identified the hyaluronan-degrading enzyme Transmembrane protein 2 (Tmem2) and we have conducted functional analyses using mouse models. These studies have unveiled the essential role of Tmem2-mediated hyaluronan degradation and its involvement in hyaluronan-mediated cell adhesion during tooth formation. This review provides a comprehensive summary of the current understanding of GAG functions in tooth development, integrating insights from recent research, and discusses future directions in this field.

Protective Effects of Hydrogen Gas Inhalation for Hindlimb Ischaemia-Reperfusion Injury in a Mouse Model.

OBJECTIVE: Ischaemia-reperfusion (I/R) injury is a severe post-operative complication that triggers an inflammatory response and causes severe damage. Hydrogen gas has anti-oxidant and anti-apoptotic properties and has been shown to be safe in humans. The study aimed to investigate whether hydrogen gas protects against skeletal muscle I/R injury. METHODS: Experimental basic research using mice. A total of 160 eight to 10 week old albino laboratory bred strain of house mice (25.8 ± 0.68 g) were used in this study. The mice were cable tied to the hindlimb under anaesthesia and then placed in an anaesthesia box filled with air and 2% isoflurane (control group); 80 mice were additionally subjected to 1.3% hydrogen gas in this mix (hydrogen group). After two hours, the cable ties were removed to initiate reperfusion, and hydrogen inhalation lasted for six hours in the hydrogen group. After six hours, the mice were taken out of the box and kept in cages under standard conditions until time for observation at 16 different time points after reperfusion: zero, two, four, six, eight, and 10 hours and one, two, three, four, five, six, seven, 14, 21, and 28 days. Five mice were sacrificed using excess anaesthesia at each time point, and the bilateral hindlimb tissues were harvested. The inflammatory effects of the I/R injury were assessed by evaluating serum interleukin-6 concentrations using enzyme linked immunosorbent assay, as well as histological and immunohistochemical analyses. Untreated mice with I/R injury were used as controls. RESULTS: Hydrogen gas showed protective effects associated with a reduction in inflammatory cell infiltration (neutrophils, macrophages, and lymphocytes), a reduced area of damaged muscle, maintenance of normal muscle cells, and replacement of damaged muscle cells with neoplastic myocytes. CONCLUSION: Inhalation of hydrogen gas had a protective effect against hindlimb I/R injury in mice, in part by reducing inflammatory cell infiltration and in part by preserving normal muscle cells.

Immediate Angiography and Decreased In-Hospital Mortality of Adult Trauma Patients: A Nationwide Study.

PURPOSE: This study aimed to elucidate whether immediate angiography within 30 min is associated with lower in-hospital mortality compared with non-immediate angiography. MATERIALS AND METHODS: We conducted a retrospective cohort study using a nationwide trauma databank (2019-2020). Adult trauma patients who underwent emergency angiography within 12 h after hospital arrival were included. Patients who underwent surgery before angiography were excluded. Immediate angiography was defined as one performed within 30 min after arrival (door-to-angio time ≤ 30 min). In-hospital mortality and non-operative management (NOM) failure were compared between patients with immediate and non-immediate angiography. Inverse probability weighting with propensity scores was conducted to adjust patient demographics, injury mechanism and severity, vital signs on hospital arrival, and resuscitative procedures. A restricted cubic spline curve was drawn to reveal survival benefits by door-to-angio time. RESULTS: Among 1,455 patients eligible for this study, 92 underwent immediate angiography. Angiography ≤ 30 min was associated with decreased in-hospital mortality (5.0% vs 11.1%; adjusted odds ratio [OR], 0.42 [95% CI, 0.31-0.56]; p < 0.001), as well as lower frequency of NOM failure: thoracotomy and laparotomy after angiography (0.8% vs. 1.8%; OR, 0.44 [0.22-0.89] and 2.6% vs. 6.5%; OR, 0.38 [0.26-0.56], respectively). The spline curve showed a linear association between increasing mortality and prolonged door-to-angio time in the initial 100 min after arrival. CONCLUSION: In trauma patients, immediate angiography ≤ 30 min was associated with lower in-hospital mortality and fewer NOM failures. LEVEL OF EVIDENCE: Level 3b, non randomized controlled cohort/follow up study.

Delta Shock Index and higher incidence of emergency surgery in older adults with blunt trauma.

PURPOSE: Vital signs are important for predicting clinical outcomes in patients with trauma. However, their accuracy can be affected in older adults because hemodynamic changes are less obvious. This study aimed to examine the usefulness of changes in vital signs during transportation in predicting the need for hemostatic treatments in older patients with trauma. METHODS: This retrospective cohort study was conducted using data from the Japan Trauma Data Bank (2004-2019). Patients aged ≥ 65 years who were hemodynamically stable at the scene were included in this study. The incidence of emergency surgery within 12 h after hospital arrival was compared between patients with delta Shock Index (dSI) > 0.1 and those with dSI ≤ 0.1. Predicting ability was examined after adjusting for patient demographics, comorbidities, vital signs at the scene and on hospital arrival, Injury Severity Score, and abbreviated injury scale in each region. RESULTS: Among the 139,242 patients eligible for the study, 3,701 underwent urgent hemostatic surgery within 12 h. Patients with dSI > 0.1 showed a significantly higher incidence of emergency surgery than those with dSI ≤ 0.1 (871/16,549 [5.3%] vs. 2,830/84,250 [3.4%]; odds ratio (OR), 1.60 [1.48-1.73]; adjusted OR, 1.22 [1.08-1.38]; p = 0.001). The relationship between high dSI and a higher incidence of intervention was observed in patients with hypertension and those with decreased consciousness on arrival. CONCLUSION: High dSI > 0.1 was significantly associated with a higher incidence of urgent hemostatic surgery in older patients.

Poly(lactic acid/caprolactone) bilayer membrane achieves bone regeneration through a prolonged barrier function.

Guided bone regeneration (GBR) is a treatment strategy used to recover bone volume. Barrier membranes are a key component of GBR protocols, and their properties can impact treatment outcomes. This study investigated the efficacy of an experimental, slow-degrading, bilayer barrier membrane for application in GBR using in vivo animal models. A synthetic copolymer of poly(lactic acid/caprolactone) (PLCL) was used to prepare a slow-degrading bilayer membrane. The biodegradability of PLCL was evaluated by subcutaneous implantation in a rat model. The barrier function of the PLCL membrane was investigated in a rat calvaria defect model and compared with commercially available membranes composed of type I collagen (Col) and poly(lactic-co-glycolic acid) (PLGA). An alveolar bone defect model in beagle dogs was used to simulate GBR protocols to evaluate the bone regeneration ability of the experimental PLCL membrane. The PLCL membrane showed slow biodegradation, resulting in an efficient and prolonged barrier function compared with commercial materials. In turn, this barrier function enabled the space-making ability of PLCL membrane and facilitated bone regeneration. In the alveolar bone defect model, significantly greater regeneration was achieved by treatment with PLCL membrane compared with Col and PLGA membranes. Additionally, a continuous alveolar ridge contour was observed in PLCL-treated bone defects. In conclusion, the PLCL bilayer membrane is a promising biomaterial for use in GBR given its slow degradation and prolonged barrier function.

Hyperoxia for sepsis and development of acute lung injury with increased mortality.

BACKGROUND: Supraphysiological oxygen administration causes unfavourable clinical outcomes in various diseases. This study aimed to determine whether hyperoxia would be associated with increased mortality in patients with severe infection. METHODS: A post-hoc analysis of a nationwide multicentre prospective observational study on sepsis (SPICE Study) was conducted, including adult patients admitted to the intensive care unit with available arterial partial pressure of oxygen (PaO2) at the treatment initiation for severe infection. Hyperoxia was defined as a PaO2 level of ≥300 mm Hg and in-hospital mortality was compared between patients with and without hyperoxia. RESULTS: Of the 563 patients eligible for the study, 49 had hyperoxia at treatment initiation for severe infection. The in-hospital all-cause mortality rates of patients with and without hyperoxia were 14 (29.2%) and 90 (17.6%), respectively. Inverse probability weighting analyses with propensity scores revealed the association between hyperoxia and increased in-hospital mortality rate (28.8% vs 18.8%; adjusted OR 1.75 (1.03 to 2.97); p=0.038), adjusting for patient demographics, comorbidities, site of infection, severity of infection, haemodynamic and respiratory status, laboratory data and location of patient at infection development. Acute lung injury developed more frequently in patients with hyperoxia on the following days after infection treatment, whereas sepsis-related mortality was comparable regardless of hyperoxia exposure. CONCLUSION: Hyperoxia with PaO2 ≥300 mm Hg at treatment initiation of severe infection was associated with an increased in-hospital mortality rate in patients requiring intensive care. The amount of oxygen to administer to patients with severe infection should be carefully determined. TRIAL REGISTRATION NUMBER: University Hospital Medical Information Network Clinical Trial Registry (UMIN000027452).

Mice Lacking PLAP-1/Asporin Show Alteration of Periodontal Ligament Structures and Acceleration of Bone Loss in Periodontitis.

Periodontal ligament-associated protein 1 (PLAP-1), also known as Asporin, is an extracellular matrix protein expressed in the periodontal ligament and plays a crucial role in periodontal tissue homeostasis. Our previous research demonstrated that PLAP-1 may inhibit TLR2/4-mediated inflammatory responses, thereby exerting a protective function against periodontitis. However, the precise roles of PLAP-1 in the periodontal ligament (PDL) and its relationship to periodontitis have not been fully explored. In this study, we employed PLAP-1 knockout mice to investigate its roles and contributions to PDL tissue and function in a ligature-induced periodontitis model. Mandibular bone samples were collected from 10-week-old male C57BL/6 (WT) and PLAP-1 knockout (KO) mice. These samples were analyzed through micro-computed tomography (µCT) scanning, hematoxylin and eosin (HE) staining, picrosirius red staining, and fluorescence immunostaining using antibodies targeting extracellular matrix proteins. Additionally, the structure of the PDL collagen fibrils was examined using transmission electron microscopy (TEM). We also conducted tooth extraction and ligature-induced periodontitis models using both wild-type and PLAP-1 KO mice. PLAP-1 KO mice did not exhibit any changes in alveolar bone resorption up to the age of 10 weeks, but they did display an enlarged PDL space, as confirmed by µCT and histological analyses. Fluorescence immunostaining revealed increased expression of extracellular matrix proteins, including Col3, BGN, and DCN, in the PDL tissues of PLAP-1 KO mice. TEM analysis demonstrated an increase in collagen diameter within the PDL of PLAP-1 KO mice. In line with these findings, the maximum stress required for tooth extraction was significantly lower in PLAP-1 KO mice in the tooth extraction model compared to WT mice (13.89 N ± 1.34 and 16.51 N ± 1.31, respectively). In the ligature-induced periodontitis model, PLAP-1 knockout resulted in highly severe alveolar bone resorption, with a higher number of collagen fiber bundle tears and significantly more osteoclasts in the periodontium. Our results demonstrate that mice lacking PLAP-1/Asporin show alteration of periodontal ligament structures and acceleration of bone loss in periodontitis. This underscores the significant role of PLAP-1 in maintaining collagen fibrils in the PDL and suggests the potential of PLAP-1 as a therapeutic target for periodontal diseases.

Persistent and Late-Onset Disseminated Intravascular Coagulation Are Closely Related to Poor Prognosis in Patients with Sepsis.

BACKGROUND: Septic-associated disseminated intravascular coagulation (DIC) is heterogeneous regarding prognosis and responsiveness to anticoagulant therapy. OBJECTIVES: To investigate the relationship between the timing of development and recovery of DIC, its prognosis, and the difference in response to anticoagulant therapy in sepsis-associated DIC patients. METHODS: This study was performed with a dataset from a multicenter nationwide retrospective cohort study (J-Septic DIC registry) in Japan between 2011 and 2013 to reveal the subgroup "high risk of death in DIC" and investigate the relationship between anticoagulant use and mortality. Patients were assigned to four groups based on the International Society on Thrombosis and Haemostasis-overt DIC status at days 1 and 3: non-DIC (-/-), early-recovered DIC (+/-), late-onset DIC (-/+), and persistent DIC (+/+). RESULTS: A total of 1,922 patients were included. In-hospital mortality in persistent and late-onset DIC patients was significantly higher than in patients with non-DIC and early-recovered DIC. This finding indicates that persistent DIC and late-onset DIC were a poor-prognosis subgroup, "high-risk" DIC. Meanwhile, patients with high-risk DIC treated with anticoagulants had significantly better outcomes than those without anticoagulants after adjusting for confounding factors. CONCLUSION: This study showed that individuals with a high risk of death, persistent DIC, and late-onset DIC were a poor-prognostic subgroup in septic DIC; however, high-risk DIC is also a subgroup that can obtain more benefits from anticoagulant therapy.

Simple parameters to identify patients treatable with early definitive fixation: A nationwide study.

INTRODUCTION: Early appropriate care (EAC) is widely accepted as a safe strategy to perform early definitive fracture fixation, and good clinical outcomes have been reported in selected, multiply injured patients, although the optimal candidate for early definitive fixation (EDF) has not been validated. The aim of this study was to identify simple clinical parameters to help select patients who could undergo EDF. METHODS: Patients with extremity injuries who underwent open reduction and internal fixation were retrospectively identified, using data from the Japan Trauma Data Bank (JTDB). Age, vital signs on hospital presentation, and the injury severity score (ISS) were examined by transforming these variables to binary categories. Patients were divided into categories based on these variables, and in-hospital mortality was compared between patients treated with EDF (EDF group) and those treated without EDF (non-EDF group) in each category. RESULTS: Of the 12,735 patients who were eligible for the analyses, 3706 (29.1 %) were managed with EDF. In-hospital mortality was significantly higher in the EDF group than in the non-EDF group among patients with a low Glasgow Coma Scale (GCS) score (<13), low systolic blood pressure (sBP) (<90 mmHg), and ISS≥15, whereas in-hospital mortality was comparable between the EDF and non-EDF groups among patients with GCS scores ≥13, sBP ≥90 mmHg, and ISS <15. DISCUSSION: In this large nationwide database of trauma patients, EDF was performed without affecting mortality in patients with GCS scores ≥13 and sBP ≥90 mmHg on hospital presentation, as well as ISS <15. These parameters might be useful as screening tools to select the candidates who could be treated with EDF safely.

Optimal tentative abdominal closure for open abdomen: a multicenter retrospective observational study (OPTITAC study).

BACKGROUND: Primary fascia closure is often difficult following an open abdomen (OA). While negative-pressure wound therapy (NPWT) is recommended to enhance successful primary fascia closure, the optimal methods and degree of negative pressure remain unclear. This study aimed to elucidate optimal methods of NPWT as a tentative abdominal closure for OA to achieve primary abdominal fascia closure. MATERIALS AND METHODS: A multicenter, retrospective, cohort study of adults who survived OA greater than 48 h was conducted in 12 institutions between 2010 and 2022. The achievement of primary fascia closure and incidence of enteroatmospheric fistula were examined based on methods (homemade, superficial NPWT kit, or open-abdomen kit) or degrees of negative pressure (<50, 50-100, or >100 mmHg). A generalized estimating equation was used to adjust for age, BMI, comorbidities, etiology for laparotomy requiring OA, vital signs, transfusion, severity of critical illness, and institutional characteristics. RESULTS: Of the 279 included patients, 252 achieved primary fascia closure. A higher degree of negative pressure (>100 mmHg) was associated with fewer primary fascia closures than less than 50 mmHg [OR, 0.18 (95% CI: 0.50-0.69), P =0.012] and with more frequent enteroatmospheric fistula [OR, 13.83 (95% CI: 2.30-82.93)]. The methods of NPWT were not associated with successful primary fascia closure. However, the use of the open-abdomen kit was related to a lower incidence of enteroatmospheric fistula [OR, 0.02 (95% CI: 0.00-0.50)]. CONCLUSION: High negative pressure (>100 mmHg) should be avoided in NPWT during tentative abdominal closure for OA.