A Pilot Study of Soluble Form of LOX-1 as a Novel Biomarker for Neonatal Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: To evaluate the soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) as a biomarker of severity staging and prognosis in neonatal hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We performed an observational study enrolling 27 infants with HIE and 45 control infants of gestational age ≥36 weeks and birth weight ≥1800 g. The HIE criteria were pH ≤7.0 or a base deficit ≥16 mmol/L within 60 minutes after birth, and a 10-minute Apgar score ≤5 or resuscitation time ≥10 minutes. HIE severity was evaluated using modified Sarnat staging. We measured plasma sLOX-1 level and assessed general and neurologic signs at discharge, and classified infants with no neurosensory impairments as intact survival. RESULTS: sLOX-1 level within 6 hours after birth was correlated with the severity of HIE. sLOX-1 differentiated moderate-severe HIE (median, 1017 pg/mL; IQR, 553-1890 pg/mL) from mild HIE (median, 339 pg/mL; IQR, 288-595 pg/mL; P = .007). The sensitivity and specificity of the differentiation with a cutoff value of ≥550 pg/mL were 80.0% and 83.3%, respectively. In 19 infants with therapeutic hypothermia, a sLOX-1 cutoff value of <1000 pg/mL differentiated intact survival (median, 761 pg/mL; IQR, 533-1610 pg/mL) from death or neurosensory impairment (median, 1947 pg/mL; IQR, 1325-2506 pg/mL; P = .019) with 100% specificity and a positive predictive value. CONCLUSION: sLOX-1 may be a useful biomarker of neonatal HIE for severity staging and outcome prediction. Further investigations will facilitate its clinical use.

Effect of i.v. immunoglobulin in the first 4 days of illness in Kawasaki disease.

BACKGROUND: Although early treatment of Kawasaki disease (KD) with i.v. immunoglobulin (IVIG) is expected to prevent coronary artery abnormalities, the effectiveness of IVIG by day 4 of illness remains to be determined. METHODS: This was a multi-institutional, retrospective cohort study. Patients diagnosed with KD at ≤4 days of illness were divided into two groups: those who received initial IVIG before and on day 5 of illness. Baseline characteristics were adjusted using propensity scores. The primary endpoint was the need for additional treatment. RESULTS: Of 339 patients diagnosed with KD by day 4, 181 and 158 received IVIG before and on day 5 of illness, respectively. Patients in the early treatment group had more adverse prognostic factors: infancy, early onset of the principal symptoms, and abnormal laboratory data. We thus adjusted baseline characteristics before treatment decisions using propensity scores. Propensity score matching of the two groups yielded 100 observations. More patients required additional treatment in the matched early treatment group: 37% vs 24% (adjusted OR, 1.7; 95%CI: 1.06-2.8; P = 0.047). The difference was more pronounced for risk of relapse after initial resolution of fever: 14% vs 5.0% (adjusted OR, 3.2; 95%CI: 1.3-7.7; P = 0.02). The risk of coronary artery lesion did not differ significantly. CONCLUSIONS: IVIG treatment by day 4 of illness is associated with the requirement for additional treatment even after adjustment of baseline characteristics. Increased resistance to IVIG when given by day 4 should be considered in order to improve the treatment regimen for early-diagnosed KD.

Fever pattern and C-reactive protein predict response to rescue therapy in Kawasaki disease.

BACKGROUND: Evidence to guide rescue therapy in refractory Kawasaki disease (KD) is lacking. The aim of this study was to determine the most important variables in predicting non-response to rescue therapy in refractory KD. METHODS: We retrospectively analyzed 171 patients diagnosed with refractory KD resistant to initial i.v. immunoglobulin (IVIG). Participants received rescue therapy consisting of IVIG monotherapy or IVIG plus prednisolone. Characteristics and laboratory variables were compared between rescue therapy non-responders and responders. Multivariate logistic regression analysis was performed to determine the independent predictors of non-response to rescue therapy. RESULTS: Among the 171 participants, 54 (31.6%) were non-responders to rescue therapy. On univariate analysis, fever pattern after initial IVIG, day of illness at rescue therapy, rescue therapy regimen and six laboratory variables (pre-IVIG sodium, C-reactive protein [CRP]; post-IVIG white blood cell count, platelet count, sodium, CRP) were useful in discriminating between non-responders and responders. These nine variables were included in multivariate logistic regression analysis. Persistent fever after initial IVIG (aOR, 2.39; 95%CI: 1.07-5.37) and post-IVIG CRP (aOR, 1.09; 95%CI: 1.02-1.17, per 1 mg/dL increase) were identified as independent predictors of non-response to rescue therapy. IVIG rescue monotherapy (aOR, 3.05; 95%CI: 1.05-8.84) also predicted non-response after adjusting for fever pattern and post-IVIG CRP. CONCLUSIONS: Persistent fever and elevated CRP after initial IVIG are predictive of non-response to rescue therapy for refractory KD. For patients at high risk of non-response, IVIG plus prednisolone, or even further intensified rescue therapy regimens may be preferable.

C2 lamina reconstruction using locking miniplate for the intradural tumor of the craniocervical junction (two case reports).

OBJECTIVE: To describe a technique for C2 lamina reconstruction using locking miniplates for the extirpation of spinal tumors in the craniocervical junction. Many spinal surgery cases in which lamina reconstructions have been performed using non-locking miniplates have been reported. However, there is only one report of the use of locking miniplates for lamina reconstruction in spinal tumor cases. METHODS: We performed C2 lamina reconstructions using locking miniplates in a patient with a spinal tumor and another with a cystic lesion. The clinical and radiologic features of both cases are reported, and the surgical technique is described. RESULTS: A 62-year-old female and a 30-year-old male were diagnosed with meningioma and a neurenteric cyst, respectively, in the craniocervical junction. Extirpation of these lesions was performed in combination with C2 lamina reconstruction and reattachment of the paraspinous muscle to the C2 spinous process. A follow-up examination at 1 year postoperatively demonstrated no significant change in the sagittal alignment of the cervical spine and a good postoperative course in both cases. Bony fusion was detected in both cases, and no implant failure occurred in either case. CONCLUSIONS: This procedure results in rigid fixation of the reimplanted C2 lamina and helps to restore the paraspinous muscles. For these reasons, it appears to be a useful surgical procedure for spinal tumors requiring C2 laminectomy and does not cause postoperative kyphosis of the cervical spine.

A case of early onset cystinuria in a 4-month-old girl.

Cystinuria is an autosomal recessive disorder characterized by a decrease in the reabsorption of cystine and dibasic amino acids (lysine, ornithine, and arginine) in the renal proximal tubule. It presents with recurrent urolithiasis. Cystinuria accounts for 6-8% of all pediatric urolithiasis. The age of onset is typically 10-30 years. Here, we report a case of early-onset cystinuria. A 4-month-old girl presented with hematuria. We noticed multiple renal calculi in ultrasonography and abdominal computerized tomography scans. The diagnosis was cystinuria with urinary calculus analysis and urinary amino acid analysis. The patient was treated with urine alkalinization and cystine chelating drugs. Gene analysis showed a P482L heterozygous mutation from her mother, and an A70V heterozygous mutation from her father, in the SLC7A9 gene. This gene encodes a putative subunit of the neutral and basic amino acid transport protein, BAT1. Although cystinuria is an autosomal recessive disease, there have been previous reports of P482L heterozygous mutations greatly suppressing cystine reabsorption and causing cystinuria symptoms. Therefore, the highly influential P482L mutation of the SLC7A9 gene may have contributed to the onset of this autosomal recessive disease at an extremely young age.

Combined radical retropubic prostatectomy and abdominoperineal excision of the rectum for locally invasive rectal cancer as a less invasive surgery: report of a case.

The optimal therapy for carcinoma of the rectum with invasion of the prostate gland has not been established. For a patient who has rectal carcinoma invading into the prostate and seminal vesicles and not invading into any other pelvic viscera, we performed combined radical retropubic prostatectomy and abdominoperineal excision of the rectum with reconstruction of the urinary tract by anastomosis of the ureter to the bladder. En bloc excision yielded negative surgical margins. After the operation, the patient had an infection of the abdominal wound and leakage of the anastomosis of the urethra to the bladder. These complications were treated conservatively and improved without becoming critical. The patient now has satisfactory postoperative function of voiding. This technique obviates the need for urinary diversion or urinary reconstruction such as the neobladder in the case of total pelvic exenteration. We consider this procedure is of benefit for improving the quality of life of patients with rectal cancer invading into the prostate.

Novel Risk Assessment Tool for Immunoglobulin Resistance in Kawasaki Disease: Application Using a Random Forest Classifier.

BACKGROUND: Resistance to intravenous immunoglobulin (IVIG) therapy is a risk factor for coronary lesions in patients with Kawasaki disease (KD). Risk-adjusted initial therapy may improve coronary outcome in KD, but identification of high risk patients remains a challenge. This study aimed to develop a new risk assessment tool for IVIG resistance using advanced statistical techniques. METHODS: Data were retrospectively collected from KD patients receiving IVIG therapy, including demographic characteristics, signs and symptoms of KD and laboratory results. A random forest (RF) classifier, a tree-based machine learning technique, was applied to these data. The correlation between each variable and risk of IVIG resistance was estimated. RESULTS: Data were obtained from 767 patients with KD, including 170 (22.1%) who were refractory to initial IVIG therapy. The predictive tool based on the RF algorithm had an area under the receiver operating characteristic curve of 0.916, a sensitivity of 79.7% and a specificity of 87.3%. Its misclassification rate in the general patient population was estimated to be 15.5%. RF also identified markers related to IVIG resistance such as abnormal liver markers and percentage neutrophils, displaying relationships between these markers and predicted risk. CONCLUSIONS: The RF classifier reliably identified KD patients at high risk for IVIG resistance, presenting clinical markers relevant to treatment failure. Evaluation in other patient populations is required to determine whether this risk assessment tool relying on RF has clinical value.

Difficulties in removal of the titanium locking plate in Japan.

OBJECTIVE: This study was designed to evaluate the frequency of intraoperative complications associated with titanium locking compression plate (LCP) removal. DESIGN: Retrospective study. METHODS: Medical records were reviewed for surgical technique, plate types used, position and number of screws, time from internal fixation to plate removal, and intraoperative complications. Radiographs were reviewed to evaluate the position of the plates and screws and the accuracy of the screw direction. Mann-Whitney and Yates Chi-square tests were calculated with the level of significance at P < 0.05. RESULTS: All LCPs could be removed. Of the 342 locking head screws (LHSs), a total of 21 (6.1%) screws, 3 (2.0%) 5.0 mm screws (3/153) and 18 (10.7%) 3.5 mm screws (18/169), were difficult to remove. The frequency of difficulty associated with the 3.5 mm LHSs was significantly higher than that of the 5.0 mm LHSs (P < 0.01). The frequency of difficulty associated with the removal of LHSs at the diaphysis was higher than that of LHSs at the epiphysis (P < 0.01), especially with 3.5 mm LHSs. The mean age was significantly lower in the patients in whom removal was difficult (P < 0.05). Our analysis revealed that the frequency of removal difficulty was high when a 3.5 mm LHS was inserted into the diaphysis of young patients. CONCLUSIONS: We should recognize that the removal of LCPs can involve numerous problems and great care should be exercised, especially in cases involving 3.5 mm LHSs.

A case of cerebral salt-wasting syndrome associated with aseptic meningitis in an 8-year-old boy.

Cerebral salt-wasting syndrome is a disorder in which excessive natriuresis and subsequent hyponatremic dehydration occur in patients with intracranial diseases. Cerebral salt-wasting syndrome often develops in patients with severe neurosurgical disorders, such as hydrocephalus, cerebral infarction, and tuberculous meningitis. Here, we report on the case of an 8-year-old boy with cerebral salt-wasting syndrome associated with aseptic meningitis. He showed mild developmental retardation and had a history of convulsion. Four days after his admission, cerebral salt-wasting syndrome abruptly started: natriuresis and hyponatremia gradually improved over 10 days. To the best of our knowledge, this is the first report on cerebral salt-wasting syndrome associated with clinically benign aseptic meningitis.