Changes in Cranial Shape and Developmental Quotient at 6 Months of Age in Preterm Infants.

The purpose of this study was to investigate changes in cranial shape among preterm neonates aged 1-6 months and the relationship between developmental quotient (DQ) and cranial shape at 6 months of age. Preterm infants who were hospitalized in our hospital were prospectively followed for 6 months. The cephalic index (CI) and cranial vault asymmetry index (CVAI) were evaluated at 1 (T1), 3 (T2), and 6 months (T3) of age and compared with those of the full-term infants. The relationship between CI or CVAI and DQ at T3 was analyzed using the Enjoji Scale of Infant Analytical Development. A total of 26 participants born at 34.7 ± 1.9 weeks of gestation were included. The CI increased with age (T1: 77.2%, T2: 82.9%, T3: 85.4%, p < 0.01). The prevalence of dolichocephaly at T3 did not significantly differ from that in full-term infants (15.4% vs. 4.5%, p = 0.08). CVAI did not significantly differ between preterm and full-term infants. The DQ showed no significant correlation with either the CI or CVAI (correlation coefficients: 0.23 for CI, -0.01; CVAI). Dolichocephaly improved over time in preterm infants and no relationship between cranial shape and development was observed in preterm infants at 6 months of age.

Cranial Shape Measurements Obtained Using a Caliper and Elastic Bands Are Useful for Brachycephaly and Deformational Plagiocephaly Screening.

We assessed a method for screening the cranial shape of 1-month-old infants using a simple measuring instrument instead of a three-dimensional scanner. The Mimos craniometer was used to measure cranial length, cranial width, and two diagonal lengths to calculate the cranial index (CI) and cranial asymmetry (CA). We defined a CI > 90% as brachycephaly and CA > 5 mm as deformational plagiocephaly (DP). Intra- and inter-examiner accuracy analyses were performed on a dummy doll and 1-month-old infants. The measurements of healthy 1-month-old infants were compared with previously reported three-dimensional scanner measurements. Intra- and inter-rater measurements showed good accuracy; diagnostic accuracy comparisons of brachycephaly and DP using a three-dimensional scanner showed kappa values of 1.0 and 0.8, respectively. Comparisons were made among 113 infants matched for day-age at the date of measurement; there were no significant differences in the CI (85.0% vs. 85.2%, p = 0.98) and CA (5.9 mm vs. 6.0 mm, p = 0.48) between the scanner and caliper measurements, nor in the prevalence of brachycephaly (12.4% vs. 17.7%, p = 0.35) or DP (58.4% vs. 56.6%, p = 0.89). This simple measurement method using calipers and bands was useful in screening for brachycephaly and DP in 1-month-old infants.

Denominator of Cranial Vault Asymmetry Index: Choosing Between Longer and Shorter Diagonal Lengths.

Since it was proposed in this journal in 2001, the cranial vault asymmetry index (CVAI) has been an important parameter for assessing cranial shape. However, different publications currently use different variables in the denominator of the CVAI formula. We thus investigated the use of long and short diagonal lengths as variables in the denominator of the CVAI formula. We searched the databases of PubMed, Google Scholar, and Scopus for articles published between 2016 and 2022 that cited the original work article of CVAI. Articles were included if they were written in English and if the denominator of the CVAI formula was specified. For multiple articles by the same author, only the most recent article was included. In total, 30 articles were included; 10 articles used the longer diagonal length as the denominator and 20 articles used the shorter diagonal length. No uniform trend was observed by a country or journal of publication. Application of the CVAI formula using different denominators yielded interchangeable results, and the resulting values had only negligible differences clinically. However, it would be necessary to create a standard formula for using the CVAI as a parameter for reporting cranial shape assessments consistently.

A rare case of sacral epidural arteriovenous fistula with concomitant occult multiple lumbar epidural arteriovenous fistulas.

We describe a rare case of sacral epidural arteriovenous fistulas (edAVFs) with atypical clinical course of treatment. A 78-year-old man with a history of spinal surgery presented progressive gait disturbance and urinary incontinence. Spinal angiography demonstrated a sacral spinal AVF fed by bilateral lateral sacral arteries, draining to the venous pouch with subdural drainage. The first treatment by direct interruption of a subdural drainer was incompletely finished. Postoperative reassessment by 3D imaging analysis led to the diagnosis of sacral edAVF and 3D understanding of its angioarchitecture. The second treatment by transarterial embolization (TAE) resulted in complete occlusion of a sacral edAVF. However, spinal venous congestion didn't improve, because the recruitment of occult edAVFs at the multiple lumbar levels and complex-shaped sacral ventral epidural venous plexus (VEP) were involved in the remnant of prior subdural drainage. The third treatment was performed by TAE for three occult edAVFs and the VEP compartment connecting between a patent edAVF and subdural drainage, which resulted in complete disappearance of spinal cord edema. Endovascular embolization of VEP compartment connecting to subdural drainage in addition to fistulous occlusion may be one of the treatment options for several edAVFs at the multiple spinal levels.

A case of subarachnoid and intracerebral hemorrhages complicated by trichosporonosis.

Background: Trichosporonosis has an extremely poor prognosis. In this report, we describe a case of subarachnoid hemorrhage and intracerebral hemorrhage due to a fungal aneurysm caused by Trichosporon. Case Description: A 71-year-old woman who experienced subcortical hemorrhage developed a subarachnoid hemorrhage. Endovascular parent artery occlusion was performed for a fungal aneurysm in the left posterior cerebral artery caused by Trichosporon. After surgery, voriconazole and liposomal amphotericin B were administered. The patient died of massive left putamen hemorrhage. Conclusion: Effective treatment for intracranial hemorrhage due to trichosporonosis has not yet been established and an accumulation of cases is required.

Evaluating Cranial Growth in Japanese Infants Using a Three-dimensional Scanner: Relationship between Growth-related Parameters and Deformational Plagiocephaly.

In this study, we aimed to evaluate the longitudinal changes in the cranial shape of healthy Japanese infants using a three-dimensional scanner and construct a normal values database for the growth process. Preterm infants (gestational age < 37 weeks), infants with neonatal asphyxia (5-minute Apgar score of <7), and patients who started helmet therapy for deformational plagiocephaly were excluded from this study. The first scan was performed at approximately 1 month of age, followed by two scans conducted at 3 and 6 months of age. The parameters considered were as follows: cranial length, width, height, circumference, volume, cranial vault asymmetry index, and cephalic index. A cranial vault asymmetry index >5% was defined as deformational plagiocephaly. Changes in each parameter were examined using repeated-measures analysis of variance classified by sex and deformational plagiocephaly status. The rate of increase in each parameter was also examined. In total, 88 infants (45 boys and 43 girls) were included in this study. All growth-related parameters were noted to increase linearly with time. Sex differences were observed in all parameters except cranial length. Deformational plagiocephaly was found to have no effect on growth-related parameters. Cranial volume increased by 60% from 1 to 6 months of age. The growth almost uniformly influenced the rate of increase in volume in each coordinate axis direction. Overall, the mean trends in three-dimensional parameters in infants up to 6 months of age were obtained using a three-dimensional scanner. These trends could be used as a guide by medical professionals involved in cranioplasty.

Cranial shapes of Japanese preterm infants at one month of age using a three-dimensional scanner.

BACKGROUND: Recently, cranial shape measurements of preterm infants have been performed using handheld three-dimensional (3D) scanners and can now be objectively quantified. AIMS: To measure the cranial shapes of Japanese preterm infants at one month of age using a 3D scanner, compare these values with those of healthy term infants, and examine the risk factors for dolichocephaly. STUDY DESIGN: A multicenter, retrospective cohort study. SUBJECTS: Preterm infants born at <37 weeks of gestation and staying in the neonatal intensive care unit or visiting an outpatient clinic for a one-month checkup between April 2020 and March 2022. OUTCOME MEASURES: A 3D scanner was used to quantify cranial shape. Comparison was made with full-term, one-month-old infants. RESULTS: Ninety-four preterm infants (42 boys) and 165 full-term infants were enrolled. Preterm infants had a significantly lower cephalic index (77.9% and 85.0%, p < 0.01) and a higher incidence of dolichocephaly (54.3% and 13.3%, p < 0.01) compared to term infants. No significant difference in incidence of deformational plagiocephaly was found between the groups (41.5% vs. 47.3%, p = 0.44). The risk of dolichocephaly was significantly higher for female sex (odds ratio [OR], 3.32; 95% confidence interval, 1.30-8.50), cesarean section (OR, 4.07; 95% confidence interval, 1.23-13.5), and use of mechanical ventilation (OR, 4.66; 95% confidence interval, 1.09-20.0). CONCLUSIONS: Japanese preterm infants at the first month of life had longer heads than full-term infants; the risk factors identified were female sex, cesarean section, and use of mechanical ventilation.

Three-Dimensional versus Two-Dimensional Evaluations of Cranial Asymmetry in Deformational Plagiocephaly Using a Three-Dimensional Scanner.

This study aimed to assess the measurement precision of a three-dimensional (3D) scanner that detects the geometric shape as surface data and to investigate the differences between two-dimensional (2D) and 3D evaluations in infants with deformational plagiocephaly. Using the 3D scanner that can perform both 2D and 3D evaluations, we calculated cranial asymmetry (CA) for the 2D evaluation, and the anterior symmetry ratio (ASR) and posterior symmetry ratio (PSR) for the 3D evaluation. Intra- and inter-examiner precision analyses revealed that the coefficients of the variation measurements were extremely low (<1%) for all variables, except CA (5%). In 530 infants, the coincidence rate of CA severity by the 2D evaluation and the 3D evaluation was 83.4%. A disagreement on severity was found between 2D and 3D evaluations in 88 infants (16.6%): 68 infants (12.8%) were assessed as severe by 2D evaluation and mild by the 3D evaluation, while 20 infants (3.8%) were evaluated as mild by 2D and severe by 3D evaluation. Overall, the 2D evaluation identified more infants as severe than the 3D evaluation. The 3D evaluation proved more precise than the 2D evaluation. We found that approximately one in six infants differed in severity between 2D and 3D evaluations.

Reference Values for Cranial Morphology Based on Three-dimensional Scan Analysis in 1-month-old Healthy Infants in Japan.

Currently, molded helmet therapy is used to treat infants with deformational plagiocephaly. However, the indices of normal cranial shape remain unclear, and thus, the prevalence of deformational plagiocephaly is unknown, particularly in Japan. We investigated the reference values for cranial morphological characteristics in 1-month-old Japanese infants using a three-dimensional scanner, to determine the prevalence of deformational plagiocephaly. One hundred fifty-three healthy infants who visited three hospitals (from April 2020 to March 2021) were enrolled. Cranial shape was measured using a three-dimensional scanner and was analyzed using image analysis software. Outcome measures were cranial volume, length, width, length-width ratio, circumference, asymmetry, and vault asymmetry index; cephalic index; and anterior, posterior, and overall symmetry ratios. The cranial vault asymmetry index >3.5% or ≥10% were diagnosed as deformational or severe deformational plagiocephaly, respectively. The mean age at measurement was 35.7 days. The mean cranial volume was 559 mL; cranial length, 129 mm; cranial width, 110 mm; length-width ratio, 118%; cephalic index, 85.2%; cranial circumference, 377 mm, cranial asymmetry, 6.4 mm; cranial vault asymmetry index, 5.0%; and anterior, posterior, and overall asymmetry ratios, 93.1%, 91.3%, and 96.4%, respectively. The prevalence of deformational and severe deformational plagiocephaly was 64.7% and 6.6%, respectively. Sex-based differences were observed for cranial volume and width. The results obtained in this study can be considered standard values that can facilitate the differentiation of abnormal infant cranial morphological characteristics for Japanese medical practitioners.

Cranial Shape in Infants Aged One Month Can Predict the Severity of Deformational Plagiocephaly at the Age of Six Months.

In this study, we aimed to monitor changes in cranial shape using three-dimensional (3D) scanning to determine whether the severity of deformational plagiocephaly (DP) at the age of 6 months could be predicted at the age of 1 month. The cranial shape was measured at the ages of 1, 3, and 6 months (T1, T2, and T3, respectively) in 92 infants. We excluded those who received helmet treatment before T3. The cranial vault asymmetry index (CVAI) using 3D scanning was evaluated in all infants. DP was defined as a CVAI > 5.0% with mild (CVAI ≤ 6.25%) or moderate/severe severity (CVAI > 6.25%). The CVAI cut-off value at T1 for severe DP at T3 was determined using receiver operating characteristic (ROC) curves. At T1, T2, and T3, the respective CVAI median values were 5.0%, 5.8%, and 4.7% and the DP incidence was 50.0%, 56.8%, and 43.2%, respectively. The DP severity temporarily worsened from T1 to T2 but then improved at T3. Among the infants, 73.9% had a similar DP severity at T1 and T3 (p = 1.0). A ROC curve analysis revealed a CVAI cut-off value of 7.8% at T1 predicted severe DP. It was concluded that later DP severity could be predicted using 3D scanning at T1 with properly defined cut-off values.

Role of Endovascular Approach as Diagnostic Technique and First-Line Therapy for the Patients with Micro-Arteriovenous Malformations: A Case Report and Literature Review.

Objective: We describe a rare case report of micro-arteriovenous malformation (micro-AVM) treated by the endovascular approach in addition with literature review. Case Presentation: A 12-year-old boy presenting with a spontaneous intracerebral hematoma in the left occipital lobe underwent conventional diagnostic workups. The results of initial catheter angiography were considered to be equivocal as the AVM. Superselective angiography (SA) demonstrated a micro or small AVM (single feeder and single drainer type) with an aneurysmal dilatation. Immediate transarterial embolization (TAE) might fail to occlude the whole of nidus area completely, and subsequently, we switched to the surgical exploration of AVM lesion. Intraoperative findings demonstrated that the whole of AVM lesion had already been occluded completely, indicating the complete occlusion by TAE only. Pathological findings of the surgical specimen showed an aneurysmal dilatation was a venous aneurysm with vulnerable vascular wall structure, which was certainly the source of bleeding. Based on the above results, the retrospective revaluation of superselective angiogram permitted us to understand that the nidus of AVM was micro nidus type and TAE had resulted in the complete nidus occlusion. Conclusion: SA is the most useful diagnostic modality to clarify the angioarchitecture of micro-AVM and AVM-related aneurysms. If SA is successfully performed and relatively safe TAE is expected to be possible, the subsequent attempt to do curative embolization as a first-line treatment may be worthy of consideration. However, the surgical procedure should be fully reserved for the possible incomplete obliteration and hemorrhagic complications.

Natural-Course Evaluation of Infants with Positional Severe Plagiocephaly Using a Three-Dimensional Scanner in Japan: Comparison with Those Who Received Cranial Helmet Therapy.

This study aimed to clarify the natural course of positional plagiocephaly using a three-dimensional (3D) scanner and investigate the effectiveness of cranial helmet therapy (CHT). One hundred infants with severe plagiocephaly who visited our institutions between April 2020 and March 2021 were included. Cranial shape was measured using an Artec Eva 3D scanner. A cranial asymmetry (CA) >12 mm was diagnosed as severe plagiocephaly. An infant whose CA subsided to <12 mm was considered to have improved naturally or by CHT. The difference in CA between the second and initial scans was defined as the improvement value (median scan interval was two months). In the natural-course group comprising 56 infants with severe plagiocephaly, 37 (66%) with a median CA of 15.6 mm exhibited no improvement after two months. In the scan age- and evaluation interval-matched case-control study, the CA value in the CHT group improved by three times that in the natural-course group (-4.6 mm [n = 33] vs. -1.55 mm [n = 24], p < 0.001). Severe plagiocephaly did not improve naturally in 66% of the cases. Therefore, CHT should be considered if the CA is >12 mm on the initial evaluation.

Unexpected reversal of stereochemistry observed in the addition of methallyltrimethylsilane to a chiral α-keto imide.

A Lewis acid-promoted nucleophilic addition of methallyltrimethylsilane to a chiral α-keto imide proceeded with stereoselectivity opposite to that predicted from Soai's report. The difference in the structure of α-keto imides between Soai's and our cases might have affected the diastereofacial selectivity.

Ultrasound assessment of translation of microbubbles driven by acoustic radiation force in a channel filled with stationary fluid.

In this report, a method is proposed to quantify the translation of ultrasound contrast agent (UCA) microbubbles driven by acoustic radiation for the detection of channels filled with stationary fluid. The authors subjected UCA microbubbles in a channel with diameters of 0.1 and 0.5 mm to ultrasound pulses with a center frequency of 14.4 MHz. The translational velocity of the UCA microbubbles increased with the sound pressure and pulse repetition frequency (PRF) of the transmitted ultrasound. The mean translational velocity reached 0.75 mm/s at a negative peak sound pressure of 2.76 MPa and a PRF of 2 kHz. This trend agreed with the theoretical prediction, which indicated that the translational velocity was proportional to the square of the sound pressure and the PRF. Furthermore, an experiment was carried out with a phantom that mimics tissue and found that the proposed method aided in detection of the channel, even in the case of a low contrast-echo to tissue-echo ratio. The authors expect to develop the proposed method into a technique for detecting lymph vessels.

Ktedonoketone and 2'-oxosattabacin, benzenoid metabolites from a thermophilic bacterium Thermosporothrix hazakensis in the phylum Chloroflexi.

A thermophilic bacterium Thermosporothrix hazakensis NBRC 105916 which belongs to the class Ktedonobacteria was investigated to explore its biosynthetic potential of secondary metabolites. UV-guided fractionation led to the identification of a new benzenoid metabolite designated ktedonoketone (6) and an α-diketone metabolite 2'-oxosattabacin (7) along with five known compounds. Compound 7 was previously described as a synthetic compound, but this is the first finding as a natural product. Compound 7 induced adipocyte differentiation at 10-20 µM and autophagy at 1-10 µM. Compound 6 showed weak inducing activity of adipocyte differentiation. The biosynthetic origin of hazakacin (3), an acyloin-type compound, was elucidated by 13C-labeled precursor-feeding experiments.

Sodium Hypochlorite Pentahydrate as a Reagent for the Cleavage of trans-Cyclic Glycols.

Sodium hypochlorite pentahydrate (NaOCl·5H2O) can be used toward the efficient glycol cleavage of trans-cyclic glycols, which are generally resistant to this transformation. Interestingly, the reaction of cis-cyclic glycols with NaOCl·5H2O is slower than that observed for the corresponding trans-isomer. This trans selectivity is in sharp contrast to traditional oxidants used for glycol cleavage. Acyclic glycols can also react efficiently with NaOCl·5H2O to form their corresponding carbonyl compounds in high yield.

A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma.

High-grade gliomas (HGGs) carry a dismal prognosis despite current treatments. We previously confirmed the safety and immunogenicity of a vaccine treatment targeting tumor angiogenesis with synthetic peptides, for vascular endothelial growth factor receptor (VEGFR) epitopes in recurrent HGG patients. In this study, we evaluated a novel vaccine therapy targeting not only tumor vasculature but also tumor cells, using multiple glioma oncoantigen (GOA)/glioma angiogenesis-associated antigen (GAAA) peptides in HLA-A2402+ recurrent/progressive HGG patients. The vaccine included peptide epitopes from four GOAs (LY6K, DEPDC1, KIF20A, and FOXM1) and two GAAAs (VEGFR1 and VEGFR2). Ten patients received subcutaneous vaccinations. The primary endpoint was the safety of the treatment. T-lymphocyte responses against GOA/GAAA epitopes and treatment response were evaluated secondarily. The treatment was well tolerated without any severe systemic adverse events. The vaccinations induced immunoreactivity to at least three vaccine-targeted GOA/GAAA in all six evaluable patients. The median overall survival time in all patients was 9.2 months. Five achieved progression-free status lasting at least six months. Two recurrent glioblastoma patients demonstrated stable disease. One patient with anaplastic oligoastrocytoma achieved complete response nine months after the vaccination. Taken together, this regimen was well tolerated and induced robust GOA/GAAA-specific T-lymphocyte responses in recurrent/progressive HGG patients.

Medulloblastoma in Older Adults: A Case Report and Literature Review.

BACKGROUND: Medulloblastoma is a malignant tumor of the posterior fossa and is predominantly seen in children younger than 15 years of age. This tumor is uncommon in adults, especially those older than 40 years of age, and reports of cases in patients older than 60 years of age are particularly rare. Although surgery and radiotherapy play important roles in treatment of medulloblastoma in adults, addition of chemotherapy is controversial, especially prior to radiotherapy. CASE DESCRIPTION: We present a case of a 63-year-old woman with an atypical medulloblastoma in the cerebellum and a lesion in the suprasellar area that did not appear to be a metastasis of the medulloblastoma. The patient underwent a subtotal resection of the cerebellar medulloblastoma, which was classified histologically as classic subtype and molecularly as non-Wingless/non-Sonic hedgehog subtype in World Health Organization 2016 classification. Then she underwent postoperative chemotherapy followed by radiotherapy. We administered chemotherapy to facilitate therapeutic diagnosis of the suprasellar lesion. The combination treatment resulted in the disappearance of the cerebellar medulloblastoma with treatment toxicity well tolerated. Additionally, the suprasellar lesion remains under control. CONCLUSIONS: Even in adults over 60 years of age, medulloblastoma should be included in the differential diagnosis of a cerebellar mass. Chemotherapy for adult medulloblastoma has the potential to be efficacious and tolerable.

A pilot study of peptide vaccines for VEGF receptor 1 and 2 in patients with recurrent/progressive high grade glioma.

OBJECT: Early-phase clinical studies of glioma vaccines have shown feasibility and encouraging preliminary clinical activity. A vaccine that targets tumor angiogenesis factors in glioma microenvironment has not been reported. Therefore, we performed a pilot study to evaluate the safety and immunogenicity of a novel vaccination targeting tumor angiogenesis with synthetic peptides for vascular endothelial growth factor (VEGF) receptor epitopes in patients with recurrent/progressive high grade gliomas. METHODS: Eight patients received intranodal vaccinations weekly at a dose of 2mg/kg bodyweight 8 times. T-lymphocyte responses against VEGF receptor (VEGFR) epitopes were assessed by enzyme linked immunosorbent spot assays. RESULTS: This treatment was well-tolerated in patients. The first four vaccines induced positive immune responses against at least one of the targeted VEGFR epitopes in the peripheral blood mononuclear cells in 87.5% of patients. The median overall survival time in all patients was 15.9 months. Two achieved progression-free status lasting at least 6 months. Two patients with recurrent GBM demonstrated stable disease. Plasma IL-8 level was negatively correlated with overall survival. CONCLUSION: These data demonstrate the safety and immunogenicity of VEGFR peptide vaccines targeting tumor vasculatures in high grade gliomas.