Association between Moraxella keratitis and advanced glycation end products.

Diabetes mellitus is recognized as a major predisposing factor for Moraxella keratitis. However, how diabetes mellitus contributes to Moraxella keratitis remains unclear. In this study, we examined Moraxella keratitis; based on the findings, we investigated the impact of advanced glycation end products (AGEs) deposition in the cornea of individuals with diabetic mellitus on the adhesion of Moraxella isolates to the cornea. A retrospective analysis of 27 culture-proven cases of Moraxella keratitis at Ehime University Hospital (March 2006 to February 2022) was performed. Moraxella isolates were identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Among the patients, 30.4% had diabetes mellitus and 22.2% had the predominant ocular condition of using steroid eye drops. The species identified were Moraxella nonliquefaciens in 59.3% and Moraxella lacunata in 40.7% of patients. To investigate the underlying mechanisms, we assessed the effects of M. nonliquefaciens adherence to simian virus 40-immortalized human corneal epithelial cells (HCECs) with or without AGEs. The results demonstrated the number of M. nonliquefaciens adhering to HCECs was significantly increased by adding AGEs compared with that in controls (p < 0.01). Furthermore, in the corneas of streptozotocin-induced diabetic C57BL/6 mice treated with or without pyridoxamine, an AGE inhibitor, the number of M. nonliquefaciens adhering to the corneas of diabetic mice was significantly reduced by pyridoxamine treatment (p < 0.05). In conclusion, the development of Moraxella keratitis may be significantly influenced by the deposition of AGEs on the corneal epithelium of patients with diabetes mellitus.

Comparative effectiveness of angioembolization versus open surgery in patients with blunt splenic injury.

The effectiveness and safety of transcatheter splenic artery embolization (SAE) compared to those of open surgery in patients with blunt splenic injury (BSI) remain unclear. This retrospective cohort-matched study utilized data from the Japan Trauma Data Bank recorded between 2004 and 2019. Patients with BSI who underwent SAE or open surgery were selected. A propensity score matching analysis was used to balance the baseline covariates and compare outcomes, including all-cause in-hospital mortality and spleen salvage. From 361,706 patients recorded in the data source, this study included 2,192 patients with BSI who underwent SAE or open surgery. A propensity score matching analysis was used to extract 377 matched pairs of patients. The in-hospital mortality rates (SAE, 11.6% vs. open surgery, 11.2%, adjusted relative risk (aRR): 0.64; 95% confidence interval [CI]: 0.38-1.09, p = 0.10) were similar in both the groups. However, spleen salvage was significantly less achieved in the open surgery group than in the SAE group (SAE, 87.1% vs. open surgery, 32.1%; aRR: 2.84, 95%CI: 2.29-3.51, p < 0.001). Survival rates did not significantly differ between BSI patients undergoing SAE and those undergoing open surgery. Nonetheless, SAE was notably associated with a higher likelihood of successful spleen salvage.

Experimental interventions attenuate a conjunctival epidermal metaplasia model.

The conjunctiva is a non-keratinized, stratified columnar epithelium with characteristics different from the cornea and eyelid epidermis. From development to adulthood, a distinguishing feature of ocular versus epidermal epithelia is the expression of the master regulator PAX6. A conditionally immortalized conjunctival epithelial cell line (iHCjEC) devoid of stromal or immune cells established in our laboratory spontaneously manifested epidermal metaplasia and upregulated expression of the keratinization-related genes SPRR1A/B and the epidermal cytokeratins KRT1 and KRT10 at the expense of the conjunctival trait. In addition, iHCjEC indicated a significant decrease in PAX6 expression. Dry eye syndrome (DES) and severe ocular surface diseases, such as Sjögren's syndrome and Stevens-Johnson syndrome, cause the keratinization of the entire ocular surface epithelia. We used iHCjECs as a conjunctiva epidermal metaplasia model to test PAX6, serum, and glucocorticoid interventions. Reintroducing PAX6 to iHCjECs resulted in upregulating genes related to cell adhesion and tight junctions, including MIR200CHG and CLDN1. The administration of glucocorticoids or serum resulted in the downregulation of epidermal genes (DSG1, SPRR1A/B, and KRT1) and partially corrected epidermal metaplasia. Our results using an isolated conjunctival epidermal metaplasia model point toward the possibility of rationally "repurposing" clinical interventions, such as glucocorticoid, serum, or PAX6 administration, for treating epidermal metaplasia of the conjunctiva.

COAGULOPATHY PARAMETERS PREDICTIVE OF OUTCOMES IN SEPSIS-INDUCED ACUTE RESPIRATORY DISTRESS SYNDROME: A SUBANALYSIS OF THE TWO PROSPECTIVE MULTICENTER COHORT STUDIES.

ABSTRACT: Background: Although coagulopathy is often observed in acute respiratory distress syndrome (ARDS), its clinical impact remains poorly understood. Objectives: This study aimed to clarify the coagulopathy parameters that are clinically applicable for prognostication and to determine anticoagulant indications in sepsis-induced ARDS. Method: This study enrolled patients with sepsis-derived ARDS from two nationwide multicenter, prospective observational studies. We explored coagulopathy parameters that could predict outcomes in the Focused Outcome Research on Emergency Care for Acute Respiratory Distress Syndrome, Sepsis, and Trauma (FORECAST) cohort, and the defined coagulopathy criteria were validated in the Sepsis Prognostication in Intensive Care Unit and Emergency Room-Intensive Care Unit (SPICE-ICU) cohort. The correlation between anticoagulant use and outcomes was also evaluated. Results: A total of 181 patients with sepsis-derived ARDS in the FORECAST study and 61 patients in the SPICE-ICU study were included. In a preliminary study, we found the set of prothrombin time-international normalized ratio ≥1.4 and platelet count ≤12 × 10 4 /µL, and thrombocytopenia and elongated prothrombin time (TEP) coagulopathy as the best coagulopathy parameters and used it for further analysis; the odds ratio (OR) of TEP coagulopathy for in-hospital mortality adjusted for confounding was 3.84 (95% confidence interval [CI], 1.66-8.87; P = 0.005). In the validation cohort, the adjusted OR for in-hospital mortality was 32.99 (95% CI, 2.60-418.72; P = 0.002). Although patients without TEP coagulopathy showed significant improvements in oxygenation over the first 4 days, patients with TEP coagulopathy showed no significant improvement (ΔPaO 2 /FiO 2 ratio, 24 ± 20 vs. 90 ± 9; P = 0.026). Furthermore, anticoagulant use was significantly correlated with mortality and oxygenation recovery in patients with TEP coagulopathy but not in patients without TEP coagulopathy. Conclusion: Thrombocytopenia and elongated prothrombin time coagulopathy is closely associated with better outcomes and responses to anticoagulant therapy in sepsis-induced ARDS, and our coagulopathy criteria may be clinically useful.

Association of Contrast Extravasation Grade With Massive Transfusion in Pediatric Blunt Liver and Spleen Injuries: A Multicenter Retrospective Cohort Study.

BACKGROUND: This study aimed to assess whether the grade of contrast extravasation (CE) on CT scans was associated with massive transfusion (MT) requirements in pediatric blunt liver and/or spleen injuries (BLSI). METHODS: This multicenter retrospective cohort study included pediatric patients (≤16 years old) who sustained BLSI between 2008 and 2019. MT was defined as transfusion of all blood products ≥40 mL/kg within the first 24 h of admission. Associations between CE and MT requirements were assessed using multivariate logistic regression analysis with cluster-adjusted robust standard errors to calculate the adjusted odds ratio (AOR). RESULTS: A total of 1407 children (median age: 9 years) from 83 institutions were included in the analysis. Overall, 199 patients (14 %) received MT. CT on admission revealed that 54 patients (3.8 %) had CE within the subcapsular hematoma, 100 patients (7.1 %) had intraparenchymal CE, and 86 patients (6.1 %) had CE into the peritoneal cavity among the overall cohort. Multivariate analysis, adjusted for age, sex, age-adjusted shock index, injury severity, and laboratory and imaging factors, showed that intraparenchymal CE and CE into the peritoneal cavity were significantly associated with the need for MT (AOR: 2.50; 95 % CI, 1.50-4.16 and AOR: 4.98; 95 % CI, 2.75-9.02, respectively both p < 0.001). The latter significant association persisted in the subgroup of patients with spleen and liver injuries. CONCLUSION: Active CE into the free peritoneal cavity on admission CT was independently associated with a greater probability of receiving MT in pediatric BLSI. The CE grade may help clinicians plan blood transfusion strategies. LEVEL OF EVIDENCE: Level 4; Therapeutic/Care management.

Trauma mechanisms and patterns of blunt cervical vascular injury: A descriptive study using a nationwide trauma registry.

OBJECTIVE: Blunt cervical vascular injury (BCVI) is a non-penetrating trauma to the carotid and/or vertebral vessels following a direct injury to the neck or by the shearing of the cervical vessels. Despite its potentially life-threatening nature, important clinical features of BCVI such as typical patterns of co-occurring injuries for each trauma mechanism are not well known. To address this knowledge gap, we described the characteristics of patients with BCVI to identify the pattern of co-occurring injuries by common trauma mechanisms. METHODS: This is a descriptive study using a Japanese nationwide trauma registry from 2004 through 2019. We included patients aged ≥13 years presenting to the emergency department (ED) with BCVI, defined as a blunt trauma to any of the following vessels: common/internal carotid artery, external carotid artery, vertebral artery, external jugular vein, and internal jugular vein. We delineated characteristics of each BCVI classified according to three damaged vessels (common/internal carotid artery, vertebral artery, and others). In addition, we applied network analysis to unravel patterns of co-occurring injuries among patients with BCVI by four common trauma mechanisms (car accident, motorcycle/bicycle accident, simple fall, and fall from a height). RESULTS: Among 311,692 patients who visited the ED for blunt trauma, 454 (0.1%) patients had BCVI. Patients with common/internal carotid artery injuries presented to the ED with severe symptoms (e.g., the median Glasgow Coma Scale was 7) and had high in-hospital mortality (45%), while patients with vertebral artery injuries presented with relatively stable vital signs. Network analysis showed that head-vertebral-cervical spine injuries were common across four trauma mechanisms (car accident, motorcycle/bicycle accident, simple fall, and fall from a height), with co-occurring injuries of the cervical spine and vertebral artery being the most common injuries due to falls. In addition, common/internal carotid artery injuries were associated with thoracic and abdominal injuries in patients with car accidents. CONCLUSIONS: Based on analyses of a nationwide trauma registry, we found that patients with BCVI had distinct patterns of co-occurring injuries by four trauma mechanisms. Our observations provide an important basis for the initial assessment of blunt trauma and could support the management of BCVI.

Accuracy of the Lacrimal Syringing Test in Relation to Dacryocystography and Dacryoendoscopy.

Purpose: This study aimed to evaluate the accuracy of the lacrimal syringing test (syringing) in relation to dacryocystography (DCG) and dacryoendoscopy (DE) in lacrimal pathway (LP) obstruction. Methods: We retrospectively reviewed 101 patients (188 LPs) who underwent syringing, cone-beam computed tomography (CBCT)-DCG, and DE to diagnose the degree and site of LP obstruction. The degree of obstruction was classified into patent, partial obstruction, and complete obstruction. The degree of LP obstruction was determined by combining the findings of DE and CBCT-DCG and was designated as DCG+DE. When differentiating complete or partial obstruction on DE was uncertain, complete or partial obstruction was assigned if the DCG showed evidence of contrast media obstruction or passage, respectively. The consistency between syringing and DCG+DE was evaluated by calculating the weighted kappa coefficient. Results: The sensitivity and specificity of syringing were 94% and 89%, respectively. The weighted Cohen's kappa value of agreement between syringing and DCG+DE was κ = 0.73 (SE = 0.04, 95% confidence interval [CI]: 0.66-0.80, p < 0.01). When divided into presaccal and postsaccal obstruction categories, the kappa values were κ = 0.40 (SE = 0.11, 95% CI: 0.19-0.62, p < 0.01) and 0.55 (SE = 0.09, 95% CI: 0.37-0.73, p < 0.01), respectively. Furthermore, when limited to common canaliculus obstruction (stenoses), which accounted for 78% (46 LPs) of the total presaccal obstructions, the kappa value was κ = 0.29 (SE = 0.12, 95% CI: 0.05-0.54, p = 0.021), which demonstrated the lowest consistency between syringing and DCG+DE. Conclusion: Syringing was "substantially" in agreement with DCG+DE in detecting the degree of LP obstruction. Moreover, syringing was a sufficiently sensitive and specific test when performed by an experienced clinician. However, distinguishing between complete and partial obstructions by syringing was sometimes difficult, particularly in the common canaliculus obstruction (stenosis).

Ocular Manifestations of Peters Plus-Like Syndrome in 8q21.11 Microdeletion Syndrome.

PURPOSE: The aim of this study was to report a case of Peters plus-like syndrome, which revealed to have an 8q21.11 microdeletion by copy number variation analysis using exome data. METHODS: A 6-month-old Japanese boy presented with bilateral corneal opacity since birth. The right eye maintained central corneal transparency with slightly inferior nasal and superior peripheral corneal opacities. The entire cornea was opacified in the left eye, particularly in the superior quadrants with vascularization, suggesting Peters anomaly. Identification of intraocular structures in the left eye was difficult; however, hypoplasia of the circumferential anterior iris stroma appeared bilaterally present, and no abnormalities were present in the posterior segment on funduscopic examination of the right eye and ultrasonography in the left eye. He had several facial malformations in addition to corneal opacity, but no other external abnormalities. General examination, including biochemical tests of blood and urine, physiological and imaging tests including abdominal echo, auditory brain stem response, brain computed tomography, and magnetic resonance imaging, showed no abnormalities. However, the patient showed intellectual disability and delayed motor development. RESULTS: Although his karyotype was normal, copy number variation analysis using exome data and subsequent quantitative polymerase chain reaction identified a de novo 4.6-Mb deletion at 8q21.11q21.13; thus, the patient was diagnosed with 8q21.11 microdeletion syndrome. CONCLUSIONS: We identified a de novo 4.6-Mb deletion at 8q21.11q21.13 in a patient with ophthalmic anterior segment dysgenesis and systemic complications, clinically diagnosed as Peters plus-like syndrome. Clinically, the 8q21.11 microdeletion syndrome shows a phenotype similar to that of Peters plus syndrome, and a genetic diagnosis is required.

Sepsis-related coagulopathy treatment based on the disseminated intravascular coagulation diagnostic criteria: a post-hoc analysis of a prospective multicenter observational study.

BACKGROUND: The development of disseminated intravascular coagulation (DIC) in patients with sepsis has been repeatedly confirmed as a factor associated with poor prognosis. Anticoagulant therapy has been expected to improve sepsis patient outcomes, whereas no randomized controlled trials have demonstrated the survival benefit of anticoagulant therapies in non-specific overall sepsis. Patient selection based on the component of "high disease severity" in addition to "sepsis with DIC" has recently proved important in identifying appropriate targets for anticoagulant therapy. The aims of this study were to characterize "severe" sepsis DIC patients and to identify the patient population benefiting from anticoagulant therapy. METHODS: This retrospective sub-analysis of a prospective multicenter study included 1,178 adult patients with severe sepsis from 59 intensive care units in Japan from January 2016 to March 2017. We examined the association of patient outcomes, including organ dysfunction and in-hospital mortality, with the DIC score and prothrombin time-international normalized ratio (PT-INR), one of the components of the DIC score, using multivariable regression models including the cross-product term between these indicators. Multivariate Cox proportional hazard regression analysis with non-linear restricted cubic spline including a three-way interaction term (anticoagulant therapy × the DIC score × PT-INR) was also performed. Anticoagulant therapy was defined as the administration of antithrombin, recombinant human thrombomodulin, or their combination. RESULTS: In total, we analyzed 1013 patients. The regression model showed that organ dysfunction and in-hospital mortality deteriorated with higher PT-INR values in the range of < 1.5 and that this trend was more pronounced with higher DIC scores. Three-way interaction analysis demonstrated that anticoagulant therapy was associated with better survival outcome in patients with a high DIC score and high PT-INR. Furthermore, we identified a DIC score ≥ 5 and PT-INR ≥ 1.5 as the clinical threshold for identification of optimal targets for anticoagulant therapy. CONCLUSIONS: The combined use of the DIC score and PT-INR helps in selecting the optimal patient population for anticoagulant therapy in sepsis-induced DIC. The results obtained from this study will provide valuable information regarding the study design of randomized controlled trials examining the effects of anticoagulant therapy for sepsis. TRIAL REGISTRATION: UMIN-CTR, UMIN000019742. Registered on November 16, 2015.

Differences in the Association Between Alcoholic Beverage Type and Serum Urate Levels Using Standardized Ethanol Content.

Importance: Differences have been observed in the association of serum urate levels with consumption of different types of alcoholic beverages. However, previous studies have not standardized the unit of intake for ethanol content, and only limited types of alcoholic beverages have been evaluated. Objective: To examine differences in the association of serum urate levels with various types of alcoholic beverages when their intakes are standardized for ethanol content. Design, Setting, and Participants: This retrospective cross-sectional study was conducted using data from participants aged 20 years or older who completed a medical checkup at St Luke's International University in Japan between October 1, 2012, and October 31, 2021. Participant demographics, blood test results, and lifestyle questionnaire data were used as covariates. Analysis was performed in December 2021. Exposures: Consumption of alcoholic beverages, including beer, sake (rice wine), shochu (Japanese spirit), wine, and whiskey. Main Outcomes and Measures: Serum urate levels were measured during the medical checkup. The beverage unit was standardized to 1 standard drink, which contained 20 g of ethanol. Multivariable linear regression including interaction terms of alcohol consumption and dominant alcoholic beverage was performed. Results: This study included 78 153 participants. Their mean (SD) age was 47.6 (12.8) years; 36 463 (46.7%) were men and 41 690 were women (53.3%). A total of 45 755 participants (58.5%) were regular alcohol drinkers. Consistent associations of serum urate levels with alcohol consumption were observed in the beer-dominant group, with ß coefficients (for 1 standard drink per day) of 0.14 mg/dL (95% CI, 0.11-0.17 mg/dL; P < .001) for men and 0.23 mg/dL (95% CI, 0.20-0.26 mg/dL; P < .001) for women. A moderate increase in serum urate levels was observed in the wine-dominant group compared with a modest and nonsignificant increase in the sake-dominant group, with ß coefficients (for 1 standard drink per day) for the latter group of 0.05 mg/dL (95% CI, -0.01 to 0.10; P = .10) for men and 0.04 mg/dL (95% CI, -0.05 to 0.14 mg/dL; P = .38) for women. Restricted cubic splines showed different patterns in associations of serum urate levels with ethanol intake by dominant alcoholic beverages. Conclusions and Relevance: The results of this study suggest that the extent of the association of serum urate levels with alcohol intake was different for alcoholic beverages even after ethanol content was standardized. Higher beer consumption among men and women was consistently associated with higher serum urate levels, whereas sake was not associated with changes in serum urate levels. Therefore, alcoholic beverage type, in addition to ethanol content, should be considered as a factor contributing to hyperuricemia.

Usefulness of resuscitative endovascular balloon occlusion of the aorta compared to aortic cross-clamping in severely injured trauma patients: Analysis from the Japan Trauma Data Bank.

Aim: To compare in-hospital mortality of severely injured trauma patients who underwent resuscitative endovascular balloon occlusion of the aorta (REBOA) or aortic cross-clamping (ACC). Methods: In this multicenter, retrospective cohort study using data from a nationwide trauma registry of tertiary emergency medical centers in Japan (n = 280), trauma patients who underwent aortic occlusion at the emergency department from 2004 to 2019 were divided into two groups according to the treatment they received: patients treated with ACC and patients who underwent placement of a REBOA catheter. Multiple imputations were used to handle the missing data. In-hospital mortality of the patients who underwent REBOA or ACC was compared using a mixed-effect logistic regression analysis and a propensity score-matching analysis, in which the confounders, including baseline patient demographics and severity, were adjusted. Results: Of 1,670 patients (1,137 with REBOA and 533 with ACC), 66% were male. The median age was 56 years, and the mortality rate was 55.2% in the REBOA group and 81.6% in the ACC group. The mixed-effect model regression analysis showed a significantly lower odds ratio for in-hospital mortality rate in the REBOA group (odds ratio 0.17; 95% confidence interval, 0.12-0.26). A similar odds ratio was observed in the propensity score matching analysis (odds ratio 0.27; 95% confidence interval, 0.18-0.40). Conclusion: Compared with ACC, REBOA use was associated with decreased mortality in severely injured trauma patients.

Clinical Trial of Autologous Cultivated Limbal Epithelial Cell Sheet Transplantation for Patients with Limbal Stem Cell Deficiency.

PURPOSE: To confirm the efficacy and safety of Good Manufacturing Practice (GMP)-compliant autologous cultivated limbal epithelial cell sheets in government-controlled clinical trials that adhered to Good Clinical Practice stipulations for patients with unilateral limbal stem cell deficiency (LSCD). DESIGN: A prospective, multicenter, open-label, uncontrolled, single-arm clinical trial. PARTICIPANTS: Ten consecutive eyes of 10 patients with unilateral LSCD were followed for 2 years after surgery. Preoperative LSCD stage was IIB in 4 eyes and III in 6 eyes. METHODS: A limbal tissue biopsy was obtained from the healthy eye, after which limbal stem cells were dissociated and cultivated on temperature-responsive culture surfaces. All cell sheets were fabricated in a GMP-grade facility under established standard operating procedures. Cell sheets were evaluated using defined shipment criteria before transplantation, and only those that met the criteria were used. The cell sheet was transplanted onto each of the patients' diseased eye after removing the conjunctival scar tissue that covered the corneal surface. The severity of LSCD was determined according to a staging method agreed on by global consensus, with eyes evaluated as being in stages IA-C representing successful corneal epithelial reconstruction. Diagnosis and staging of LSCD were determined by the trial's Eligibility Judgment Committee and Effect Assessment Committee using slit-lamp photographs including fluorescein staining. Both committees comprised 2 or 3 third-party cornea specialists, who were provided with information anonymously and randomly. MAIN OUTCOME MEASURE: Corneal epithelial reconstruction rate was the primary end point. RESULTS: Corneal epithelial reconstruction was successful in 6 of 10 eyes (60%) 1 year postoperatively and was significantly higher than the 15% clinically significant efficacy rate achieved by allogeneic limbal transplantation. The reconstruction rate was 70% of eyes 2 years postoperatively. Additionally, improvements in visual acuity were noted in 50% and 60% of eyes at 1 and 2 years, respectively. No clinically significant transplantation-related adverse events were observed. CONCLUSIONS: The efficacy and safety of cultivated limbal epithelial cell sheet transplantation were thus confirmed, and the cell sheet, named "Nepic," is now approved as a cellular and tissue-based product in Japan. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Comparison between the CASIA SS-1000 and Pentacam in measuring corneal curvatures and corneal thickness maps.

PURPOSE: To compare the intra-device repeatability and inter-device reproducibility between two anterior segment imaging instruments, the CASIA SS-1000 (Tomey Corp., Nagoya, Japan) and Pentacam (OCULUS, Arlington, WA) in measuring anterior segment parameters. METHODS: Single-center, prospective clinical trial. Participants ≥20 years of age were included. One eye was randomly selected, each imaged by three CASIA SS-1000 devices and three Pentacam devices by three different examiners. Each photographer operated a pair of devices, one CASIA SS-1000 and one Pentacam. The image order for each participant was determined by a random permutation table. Three images were taken from each device. A total of 18 images were taken for each eye. Ratios of the standard deviations, referenced as (CASIA/Pentacam), were calculated to compare the repeatability and reproducibility of the two imaging instruments. RESULTS: In all, 66 participants with a mean age of 46.4 years (±21.7) were enrolled in the study. All repeatability ratios and intra-device variability were less than 1 (anterior corneal curvature: flat = 0.86, steep = 0.85; posterior corneal curvature: flat = 0.43, steep = 0.61; and map: thinnest = 0.22; central = 0.24, 2 mm = 0.26, 4 mm = 0.27, and 6 mm = 0.30). All reproducibility ratios, which measure the inter-device variability, were less than 1 (anterior corneal curvature: flat = 0.58, steep = 0.73; posterior corneal curvature: flat = 0.25, steep = 0.31; and pachymetry map: thinnest = 0.20; central = 0.20; 2 mm = 0.20; 4 mm = 0.19; and 6 mm = 0.22). A ratio of less than 1 indicates that the CASIA SS-1000 has more consistent measurements. CONCLUSIONS: The CASIA SS-1000 was found to have better repeatability and reproducibility compared to the Pentacam for both corneal curvature and pachymetry maps. This greater consistency may require further study to determine whether the decreased variability can be translated into improved clinical results.

Therapeutic strategies for pseudoaneurysm following blunt liver and spleen injuries: A multicenter cohort study in the pediatric population.

BACKGROUND: Little guidance exists for the treatment of pseudoaneurysm (PA) following pediatric blunt liver and/or spleen injuries (BLSIs). We aimed to describe the incidence of delayed PA development and the subsequent clinical course of PA in pediatric BLSIs. METHODS: This multicenter retrospective cohort study from Japan included pediatric patients (16 years and younger) who sustained BLSIs from 2008 to 2019. The cohort was divided into four groups based on hemostatic intervention within 48 hours of admission, namely, nonoperative management (NOM), NOM with interventional radiology (IR), operative management (OM), and combined IR/OM. Descriptive statistics were used to describe the incidence of delayed PA among the groups and to characterize the clinical course of any PAs. RESULTS: A total of 1,407 children (median age, 9 years) from 83 institutions were included. The overall number (incidence) of cases of delayed PA formation was 80 (5.7%), and the number with delayed PA rupture was 16 cases (1.1%) in the entire cohort. Patients treated with NOM (1,056), NOM with IR (276), OM (53), and combined IR/OM (22) developed 43 (4.1%), 32 (12%), 2 (3.8%), and 3 (14%) delayed PAs, respectively. Among patients who developed any PAs, 39% of patients underwent prophylactic IR for unruptured PA, while 13% required emergency angioembolization for delayed PA rupture, with one ruptured case requiring total splenectomy. At least 45% of patients experienced spontaneous resolution of PA without any interventions. CONCLUSION: Our results suggest that the risk of delayed PA still exists even after acute phase IR as an adjunct to NOM for BLSIs in children, indicating the necessity of a period of further observation. While endovascular interventions are usually successful for PA management, including rupture cases, given the high incidence of spontaneous resolution, the ideal management of PA remains to be investigated in future studies. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Association of antithrombin with development of trauma-induced disseminated intravascular coagulation and outcomes.

Introduction: Trauma activates the innate immune system to modulate hemostasis and minimize the damage caused by physiological bodily responses, including the activation of coagulation. Sufficiently severe trauma overwhelms physiological responses and elicits the systemic inflammatory response syndrome, which leads to the onset of disseminated intravascular coagulation (DIC), characterized by dysregulated inflammatory coagulofibrinolytic responses. Impaired anticoagulant mechanisms, including antithrombin, constitutes the pathology of DIC, while the dynamics of antithrombin and relevance to outcomes in trauma-induced coagulopathy have not been fully elucidated. This study investigated the associations of antithrombin activity with DIC onset and outcomes in severely injured patients. Methods: This retrospective sub-analysis of a multicenter, prospective study included patients with an injury severity score ≥16. We characterized trauma patients with low antithrombin activity (antithrombin <80% on hospital arrival, n = 75) in comparison with those who had normal antithrombin activity (antithrombin ≥80%, n = 200). Global markers of coagulation and fibrinolysis, molecular biomarkers for thrombin generation (soluble fibrin [SF]), and markers of anticoagulation (antithrombin) were evaluated to confirm the associations of antithrombin with DIC development and outcomes, including in-hospital mortality and the multiple organ dysfunction syndrome (MODS). Results: Patients with low antithrombin activity had higher prevalence of shock, transfusion requirements, and in-hospital mortality. Higher DIC scores and more severe organ dysfunction were observed in the low AT group compared to that in the normal AT group. Antithrombin activity on arrival at the hospital was an independent predictor of the development of DIC in trauma patients, and levels of SF increased with lower antithrombin values (antithrombin activity > 85%). Antithrombin activity at 3 h showed good predictive performance for in-hospital mortality, and a multivariable Cox proportional-hazard regression model with a cross-product term between the antithrombin and DIC showed that the in-hospital mortality in patients with DIC increased with decreased antithrombin activity. A multivariable logistic regression model showed that the odds for the development of MODS in patients with DIC increased with lower antithrombin values. Conclusion: Decreased antithrombin activity in trauma-induced coagulopathy is associated with poor outcomes through worsening of DIC.

Optimal target blood pressure in elderly with septic shock (OPTPRESS) trial: study protocol for a randomized controlled trial.

BACKGROUND: Hemodynamic stabilization is a core component in the resuscitation of septic shock. However, the optimal target blood pressure remains debatable. Previous randomized controlled trials suggested that uniformly adopting a target mean arterial pressure (MAP) higher than 65 mmHg for all adult septic shock patients would not be beneficial; however, it has also been proposed that higher target MAP may be beneficial for elderly patients, especially those with arteriosclerosis. METHODS: A multicenter, pragmatic single-blind randomized controlled trial will be conducted to compare target MAP of 80-85 mmHg (high-target) and 65-70 mmHg (control) in the resuscitation of septic shock patients admitted to 28 hospitals in Japan. Patients with septic shock aged ≥65 years are randomly assigned to the high-target or control groups. The target MAP shall be maintained for 72 h after randomization or until vasopressors are no longer needed to improve patients' condition. To minimize the adverse effects related to catecholamines, if norepinephrine dose of ≥ 0.1 µg/kg/min is needed to maintain the target MAP, vasopressin will be initiated. Other therapeutic approaches, including fluid administration, hydrocortisone use, and antibiotic choice, will be determined by the physician in charge based on the latest clinical guidelines. The primary outcome is all-cause mortality at 90 days after randomization. DISCUSSION: The result of this trial will provide great insight on the resuscitation strategy for septic shock in the era of global aged society. Also, it will provide the better understanding on the importance of individualized treatment strategy in hemodynamic management in critically ill patients. TRIAL REGISTRATION: UMIN Clinical Trials Registry; UMIN000041775. Registered 13 September 2020.

Effects of tranexamic acid on coagulofibrinolytic markers during the early stage of severe trauma: A propensity score-matched analysis.

Tranexamic acid (TXA) reduces the risk of bleeding trauma death without altering the need for blood transfusion. We examined the effects of TXA on coagulation and fibrinolysis dynamics and the volume of transfusion during the early stage of trauma. This subanalysis of a prospective multicenter study of severe trauma included 276 patients divided into propensity score-matched groups with and without TXA administration. The effects of TXA on coagulation and fibrinolysis markers immediately at (time point 0) and 3 hours after (time point 3) arrival at the emergency department were investigated. The transfusion volume was determined at 24 hours after admission. TXA was administered to the patients within 3 hours (median, 64 minutes) after injury. Significant reductions in fibrin/fibrinogen degradation products and D-dimer levels from time points 0 to 3 in the TXA group compared with the non-TXA group were confirmed, with no marked differences noted in the 24-hour transfusion volumes between the 2 groups. Continuously increased levels of soluble fibrin, a marker of thrombin generation, from time points 0 to 3 and high levels of plasminogen activator inhibitor-1, a marker of inhibition of fibrinolysis, at time point 3 were observed in both groups. TXA inhibited fibrin(ogen)olysis during the early stage of severe trauma, although this was not associated with a reduction in the transfusion volume. Other confounders affecting the dynamics of fibrinolysis and transfusion requirement need to be clarified.

Clinical characteristics of lacrimal drainage pathway disease-associated keratopathy.

PURPOSE: To report the clinical characteristics of 13 cases of noninfectious corneal ulceration related to lacrimal drainage pathway disease. METHODS: Medical records of 13 patients with lacrimal drainage pathway disease-associated keratopathy who were examined at Ehime University Hospital between April 2007 and December 2021 were analyzed. RESULTS: The predisposing lacrimal drainage pathway diseases for corneal ulceration were chronic dacryocystitis in seven patients and lacrimal canaliculitis in six patients. The corneal ulcers were located at the peripheral cornea in 10 patients and the paracentral cornea in three patients. All patients indicated few cellular infiltrations of the ulcerated area at the slit-lamp examination. Corneal perforation was found in seven patients. The primary identified organisms were Streptococcus spp. in chronic dacryocystitis and Actinomycetes spp. in lacrimal canaliculitis. All patients showed rapid healing of the epithelial defects after treatment of the lacrimal drainage pathway disease. The mean time elapsed between treatment of the lacrimal drainage pathway disease and re-epithelialization of corneal ulcer was 14.5 ± 4.8 days. CONCLUSION: Lacrimal drainage pathway disease-associated keratopathy may be characterized by peripheral corneal ulcer with few cellular infiltrations, occasionally leading to corneal perforation. Treatment of the lacrimal drainage pathway disease could be the most effective treatment for lacrimal drainage pathway disease-associated keratopathy.

Comparison of the efficacies of 1.0 and 1.5 mm silicone tubes for the treatment of nasolacrimal duct obstruction.

This retrospective observational study analyzed the postoperative outcomes of bicanalicular intubation using different diameters of tube stents for treating postsaccal nasolacrimal duct obstruction. A total of 130 patients diagnosed with postsaccal obstruction who underwent endoscopic-assisted silicone tube intubation were included in the study. Patients intubated with a 1.5-mm large-diameter tube were designated as the LD group, and those with a 1.0-mm normal-diameter tube were designated as the ND group. The patency rates of the two groups at 1 year after tube removal were compared using the Kaplan-Meier curve and restricted mean survival time (RMST) method with τ = 365 days. Results demonstrated that the recurrence rate after tube removal was significantly lower in the LD group as compared with the ND group (p = 0.001). The patency rates at 1 year after removal in the LD and ND group were 85.7% (95% confidence interval [CI]: 75.4, 91.9) and 73.9% (95% CI: 61.7, 82.8), respectively. When comparing the patency rates by the RMST method at τ = 365 days, the RMST difference, RMST ratio, and RMTL ratio were higher in the LD group at p = 0.045, 0.052, and 0.046, respectively.

Age-related differences in the survival benefit of the administration of antithrombin, recombinant human thrombomodulin, or their combination in sepsis.

Disseminated intravascular coagulation (DIC) is one of the major organ dysfunctions associated with sepsis. This retrospective secondary analysis comprised data from a prospective multicenter study to investigate the age-related differences in the survival benefit of anticoagulant therapy in sepsis according to the DIC diagnostic criteria. Adult patients with severe sepsis based on the Sepsis-2 criteria were enrolled and divided into the following groups: (1) anticoagulant group (patients who received anticoagulant therapy) and (2) non-anticoagulant group (patients who did not receive anticoagulant therapy). Patients in the former group were administered antithrombin, recombinant human thrombomodulin, or their combination. The increases in the risk of hospital mortality were suppressed in the high-DIC-score patients aged 60-70 years receiving anticoagulant therapy. No favorable association of anti-coagulant therapy with hospital mortality was observed in patients aged 50 years and 80 years. Furthermore, anticoagulant therapy in the lower-DIC-score range increased the risk of hospital mortality in patients aged 50-60 years. In conclusion, anticoagulant therapy was associated with decreased hospital mortality according to a higher DIC score in septic patients aged 60-70 years. Anticoagulant therapy, however, was not associated with a better outcome in relatively younger and older patients with sepsis.