Essentials for early diagnosis of primary intramedullary spinal cord lymphoma. How to suspect primary intramedullary spinal cord lymphoma early and proceed to invasive biopsy? A case report and literature review.

Background: Primary intramedullary spinal cord lymphoma (PISCL) is an extremely rare condition. Early diagnosis is very difficult due to the nonspecific clinical and imaging findings. A biopsy is essential for a definitive diagnosis, but courage is required to perform the surgery. Here, we present a case of PISCL and suggest useful indicators for accurate diagnosis of this pathological entity. Case Description: A 70-year-old woman presented with subacute bilateral lower-limb paralysis, disturbance of warm and pain sensations, and vesicorectal disturbance. Magnetic resonance imaging showed a contrast-enhanced mass from C7 to Th2 and large, edematous lesions from the upper cervical to lower thoracic spinal cord. Elevated uptake of 18F-fluoro-2-deoxy-D-glucose (FDG) was identified in the enhanced regions on FDG-positron emission tomography (PET). Cerebrospinal fluid (CSF) analysis revealed highly elevated levels of ß2-microglobulin (ß2-MG). Steroid pulse therapy and therapeutic plasma exchange were performed for suspected myelitis, but symptoms did not improve. Spinal cord biopsy was, therefore, performed for treatment-resistant myelopathy. Histopathological examination revealed diffuse large B-cell lymphoma, which was diagnosed as PISCL because systemic examination showed no other findings suggestive of malignant lymphoma. Conclusion: In cases with poor response to treatment and a progressive course, PISCL should be considered, and spinal cord biopsy should be performed if PET shows increased 18F-FDG uptake and ß2-MG is elevated in CSF.

Cardiac tamponade complicating esophagectomy and retrosternal gastric tube reconstitution in a patient with an abnormal ascending aorta position: a case report.

BACKGROUND: Cardiac tamponade is a rare postoperative complication of esophageal cancer surgery, which leads to rapid hemodynamic changes and can be fatal if not treated properly and promptly. Herein, we report a case of cardiac tamponade after thoracoscopic subtotal esophagectomy and retrosternal gastric tube reconstitution for esophageal cancer that was successfully treated with surgical drainage. CASE PRESENTATION: An 86-year-old man with lower thoracic esophageal cancer underwent thoracoscopic subtotal esophagectomy and retrosternal gastric tube reconstitution. No intra-operative complications were observed. On the first postoperative day, tachycardia and hypotension were observed, and pericardial effusion was identified on computed tomography images. The patient was diagnosed with obstructive shock secondary to cardiac tamponade. As percutaneous puncture drainage was not possible due to the presence of a retrosternal gastric tube, pericardiotomy with a small left anterior thoracotomy was performed, and a large amount of hematogenous fluid was drained, which instantly improved circulation. On the second postoperative day, the patient showed decreased pulse pressure, and computed tomography revealed a residual and enlarged hematoma around the right ventricle. The patient underwent surgical drainage and another pericardiotomy with a small right anterior thoracotomy was performed to drain the hematoma. At this time, multiple injuries to the fatty tissue, epicardium, and myocardium with active bleeding were observed on the anterior surface of the right ventricle near the root of the pulmonary artery. In this patient, the ascending aorta ran further to the right and dorsal sides than usual, causing the anterior wall of the right ventricle near the root of the pulmonary artery to be closer to the back of the sternum. This abnormality may have contributed to injury during the creation of the retrosternal pathway, leading to cardiac tamponade. CONCLUSIONS: Cardiac tamponade after esophagectomy can occur because of manipulation during creation of the retrosternal route, with an anomaly in the aortic position being present in this case. Gentle manipulation and selection of the reconstruction route according to the patient's condition are necessary in cases with such anatomical abnormalities.

Episodic ataxia type 2 with a novel missense variant (Leu602Arg) in CACNA1A.

Autosomal dominant episodic ataxia type 2 (EA2) is caused by variants in CACNA1A. We examined a 20-year-old male with EA symptoms from a Japanese family with hereditary EA. Cerebellar atrophy was not evident, but single photon emission computed tomography showed cerebellar hypoperfusion. We identified a novel nonsynonymous variant in CACNA1A, NM_001127222.2:c.1805T>G (p.Leu602Arg), which is predicted to be functionally deleterious; therefore, this variant is likely responsible for EA2 in this pedigree.

Analysis of factors associated with undescended testis in patients with congenital diaphragmatic hernia.

PURPOSE: This study aimed to investigate the incidence and clinical factors associated with undescended testes (UDT) in patients with congenital diaphragmatic hernia (CDH). METHODS: We retrospectively reviewed the incidence of UDT in male neonates admitted to our institution and underwent surgery for CDH between January 2006 and December 2022. Patients were divided into two groups based on the presence or absence of UDT, and risk factors for UDT were compared between the two groups. RESULTS: Among the 66 male neonates with CDH, 16 (24.2%) developed UDT. Patients with UDT had a significantly smaller gestational age (p = 0.026), lower birth weight (p = 0.042), and lower Apgar score at 1 min (p = 0.016) than those without UDT. They had a significantly higher incidence of large diaphragmatic defects (p = 0.005), received more patch closures (p = 0.020), had a longer mechanical ventilation period (p = 0.034), and longer hospital stay (p = 0.028). Multiple logistic regression analysis revealed that large diaphragmatic defect was an independent risk factor for UDT (adjusted odds ratio of 3.87). CONCLUSION: CDH and UDT are strongly correlated. In patients with CDH, the incidence of UDT was related not only to patients' prematurity but also to the large diaphragmatic defect. Large diaphragmatic defect is an independent risk factor for UDT in patients with CDH.

Feasibility and safety of laparoscopic tumor resection in children with abdominal neuroblastomas.

PURPOSE: This study aimed to evaluate the feasibility and safety of laparoscopic resection of abdominal neuroblastoma by comparing operative and long-term oncologic outcomes between open and laparoscopic surgeries. METHODS: This single-center retrospective study included patients who underwent laparoscopic tumor resection, between January 2000 and June 2021, with a maximum tumor diameter of ≤ 60 mm and without image-defined risk factors (IDRFs) at surgery. Data from 35 abdominal neuroblastoma resections were reviewed and compared between the laparotomy and laparoscopic groups. RESULTS: Nineteen patients underwent laparotomy and 16 had laparoscopic tumor resection. All laparoscopic surgeries achieved complete resection without conversion to open surgery. Median blood loss was significantly lower in the laparoscopic group (0.6 mL/kg) than in the laparotomy group (8.4 mL/kg) (P < 0.0001). There were two locoregional recurrences in the laparoscopic group and two metastatic recurrences in the laparotomy group. Five-year overall survival was 93.8% in both groups. CONCLUSION: Laparoscopic resection of abdominal neuroblastomas in children is a feasible and safe procedure for tumors ≤ 60 mm in diameter with no IDRFs at surgery, with long-term outcomes equivalent to laparotomy.

Thoracoscopic segmentectomy for congenital pulmonary airway malformation arising in a lung with an accessory fissure: A case report.

Congenital pulmonary airway malformation is a rare congenital lung lesion. This report documents the successful application of thoracoscopic segmentectomy in a 1-year-old boy prenatally diagnosed with congenital pulmonary airway malformation. Preoperative imaging studies revealed a microcystic lesion with a region of consolidation in the middle area of the right lung. Elective thoracoscopic resection was performed when the patient was aged 1 year and 4 months. Intraoperatively, the superior segment of the right lower lobe was partially separated from the normal lower lobe by a superior accessory fissure. A solid mass, fused with this segment, shared the visceral pleura. Thoracoscopic segmentectomy was successfully performed, and the patient had an uneventful postoperative course. Histological examination revealed congenital pulmonary airway malformation stocker type 2. Thoracoscopic segmentectomy is a viable surgical option that preserves the normal lung parenchyma in pediatric patients with congenital pulmonary airway malformation.

Dermal advanced glycation end-product accumulation is associated with sarcopenia-related measures in middle-aged and older men.

AIMS: Sarcopenia is the age-associated atrophy of muscles, and advanced glycation end-products (AGEs) accumulate in patients with age-associated diseases. We aimed to investigate the relationship between AGE accumulation in the skin and sarcopenia in middle-aged and older Japanese people. MATERIALS AND METHODS: We enrolled 240 participants in this cross-sectional study. The participants consisted of 120 men (mean age 68.8 ± 10.1 years) and 120 women (mean age 67.4 ± 9.0 years). The level of dermal AGE accumulation in the forearms was measured using skin autofluorescence (SAF) and many parameters associated with sarcopenia, including grip strength and thigh muscle cross-sectional area (CSA), were evaluated during medical check-ups at the Ehime University Hospital. RESULTS: Grip strength and thigh muscle CSA were significantly higher in men than women, but mean SAF did not significantly differ between them. There were significant correlations of age, height, C-reactive protein, glycated hemoglobin, grip strength, and thigh muscle CSA with SAF in men, but only age in women. Multivariate analysis showed that SAF was significantly independently associated with low grip strength in men (ß =-0.211, p =0.046). The men were then allocated to four groups according to their grip strength and thigh muscle CSA, and SAF was significantly higher in the lowgrip strength/low-thigh muscle CSA group than in the high-grip strength/high-thigh muscle CSA group (low/low group 2.25 ± 0.37 and high/high group 1.93 ± 0.36, p =0.001). CONCLUSIONS: SAF is associated with sarcopenia-related measures, especially grip strength, in middle-aged and older Japanese men, but not women.

Physiological comfort evaluation under different airflow directions in a heating environment.

BACKGROUND: Indoor airflow and thermal comfort are difficult to assess through subjective evaluations because airflow sensations can differ based on various factors, such as personal characteristics, interests, preferences, and the current state of mind. Thus, subjective evaluations should be combined with objective assessments, such as physiological measurements. This study evaluated airflow and thermal comfort through physiological measurements, including skin temperature, electroencephalography, respiration, and electrocardiography, in addition to subjective evaluations. METHODS: Twenty participants entered a test room at 30 °C after staying in an acclimation room at 18 °C for 20 min. They were exposed to indirect and direct airflow toward their faces and performed four tasks under each condition: resting, counting to 10 s following time alerts, counting to 10 s in the mind, and mental calculation. The mean speed of the air directed to the participants' faces was 0.123 m/s and 0.225 m/s in the indirect and direct conditions, respectively. RESULTS: The gamma and beta bands of electroencephalograms taken at the left-temporal (T3) and left-parietal (P7) sites showed significantly lower amplitudes under the indirect condition (gamma, T3: p = 0.034, P7: p = 0.030; beta, T3: p = 0.051, P7: p = 0.028). Similarly, the variability of respiration was lower under the indirect condition (p < 0.010). The amplitudes of gamma and beta waves showed significant correlations with anxiousness levels (gamma, T3: r = 0.41; beta, T3: r = 0.35). CONCLUSIONS: Our results suggest that indirect heating airflow causes lower mental stress and fatigue than those induced by direct flow, which is equivalent to more comfort. The results of this study suggest that physiological measurements can be used for the evaluation of unconscious indoor comfort, which cannot be detected by subjective evaluations alone.

[A Case of Metastatic Liver Tumor from Colon Cancer with Preoperative Diagnosis Obtained by Immunohistochemical Analysis of Cytologic Specimen].

CASE: A woman in her 50s underwent sigmoid colectomy and D3 lymph node dissection for sigmoid cancer(pT3, N0, M0, Stage Ⅱ: Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma 9th). She received adjuvant chemotherapy with capecitabine. Seven months after surgery, contrast-enhanced computed tomography( CECT) scan revealed a small mass in the segment 2 (S2) of the liver with dilation of peripheral intrahepatic bile duct, and the size of this mass and the bile duct dilatation were gradually increased. FDG positron emission tomography(FDG-PET)/CT showed abnormal FDG uptakes in the lesion of S2, and EOB-MRI detected other small lesions in the S6 and S7. Considering the results of image examinations, multiple lesions intrahepatic cholangiocarcinoma was firstly assumed. However, immunohistochemistry of the tumor obtained by endoscopic retrograde cholangiopancreatography (ERCP) showed cytokeratin 7-negative. Based on preoperative diagnosis of liver metastasis from colon cancer rather than intrahepatic cholangiocarcinoma, we performed left lobectomy, partial hepatectomy of S6 and S7 and cholecystectomy. In the resected specimen, the tumor was macroscopically located in the intrahepatic bile ducts. Microscopically, there existed atypical epithelial cells with glandular duct-like structure, and the lesions was histopathologically diagnosed as metastasis from colon cancer. She was discharged on the 10th postoperative day, and she is alive without recurrence one year after surgery.

Intra-abdominal desmoid-type fibromatosis successfully resected using laparoscopic fluorescence imaging with indocyanine green after intersphincteric resection for rectal cancer.

Successful resection of intra-abdominal tumors using indocyanine green (ICG) fluorescence imaging has not been reported. Here, we report a rare case of an intra-abdominal desmoid-type fibromatosis successfully resected using this technique after intersphincteric resection (ISR) for rectal cancer. One year after ISR for rectal cancer in a 47-year-old man, computed tomography showed a 50-mm intra-abdominal tumor near the left common iliac vein. Surgical resection was performed. The tumor was located in the mesentery of the remnant rectum after ISR. ICG fluorescence imaging confirmed the blood supply to the mesentery of the distal remnant rectum after tumor excision. The anal canal was successfully preserved without creating a permanent colostomy. The tumor was safely resected with resection margins, diagnosed as desmoid-type fibromatosis. No tumor recurrence was observed 6 months post-resection. This was the first case report to demonstrate the utility of this technique for an intra-abdominal tumor resection.

Physiological and subjective comfort evaluation under different airflow directions in a cooling environment.

Indoor comfort is influenced by airflow direction, but subjective evaluations can differ. This study evaluates the airflow comfort with subjective assessments and physiological measurements, including skin temperature, electroencephalograms, and electrocardiograms. Nineteen participants entered a test room at 20°C after staying in a room at 32°C for acclimation. They were exposed to indirect and direct airflow conditions to their faces and performed four tasks under each condition: resting, counting to 10 s following time alerts, counting to 10 s in mind, and mental calculation. Subjective assessments showed relatively higher thermal sensation and pleasantness under indirect airflow. The psychological time calculated from counting behaviors was longer under indirect airflow, indicating suppression of negative emotions. The face temperatures significantly declined during experiments under direct airflow. The beta and gamma bands of electroencephalograms were inhibited under the indirect condition, and these amplitudes were negatively correlated with pleasant feelings. Electrocardiogram parameters indicated that sympathetic nervous activity was predominant during counting, following alerts and mental calculation in indirect airflow. This study supports the comfort of indirect airflow based on reliable evidence.

Intravaginal administration of estradiol benzoate capsule for estrus synchronization in goats.

Estrus synchronization requires multiple treatments of hormonal drugs, requiring considerable time and cost. The aim of the present study was to develop an estrus synchronization protocol using intravaginal administration of estradiol benzoate (EB) capsules in goats. Two types of capsules were prepared: an EB capsule that melted immediately after administration and a sustained-release (SR) EB capsule that dissolved slowly and reached a peak after 24 h. Goats with functional corpus lutea were intramuscularly treated with prostaglandin F2α (PG). At 24 h after PG administration, goats were administered 1 mg of EB solution intramuscularly (PG + 24IM; n = 6) or 1 mg of EB capsule intravaginally (PG + 24EB; n = 6). The SR EB capsule was administered intravaginally at the time of PG administration (PG + SR; n = 6). The control group (n = 6) received only PG. All groups showed estrus within 72 h after PG administration. The onset of estrus did not differ significantly between the PG + 24IM and PG + SR groups but was earlier than in the control group. Estradiol concentration in the PG + SR group peaked at 11.5 ± 6.1 h after EB and PG administration. Peak estradiol concentrations were not significantly different between the PG + 24IM and PG + SR groups (78.0 ± 25.8 and 64.0 ± 38.1 pg/ml, respectively), and were higher than the PG + 24EB and control groups (27.3 ± 8.8 and 14.6 ± 6.1 pg/ml, respectively). These results suggest that intravaginal administration of an EB capsule with a sustained-drug release base is applicable for estrus synchronization, as an alternative to intramuscular administration.

Casein Hydrolysate Containing Milk-Derived Peptides Reduces Facial Pigmentation Partly by Decreasing Advanced Glycation End Products in the Skin: A Randomized Double-Blind Placebo-Controlled Trial.

Casein hydrolysate has been shown to improve arterial stiffness as estimated by brachial-ankle pulse wave velocity (baPWV) in untreated hypertensive patients. Facial pigmentation is associated with atherosclerosis, both of which are supposed to be modulated by tissue accumulation of advanced glycation end products (AGEs). However, effects of casein hydrolysate on facial pigmentation and AGEs remain largely unknown. This randomized double-blind placebo-controlled trial evaluated whether and how casein hydrolysate improves facial pigmentation in 80 nonhypertensive Japanese patients. Study participants were randomly assigned to receive either active tablets containing casein hydrolysate or placebo for 48 weeks. Facial pigmentation area, baPWV, and skin accumulation levels of AGEs were evaluated by Robo Skin Analyzer RSA50S II, volume-plethysmographic apparatus, and AGE Reader, respectively, at baseline and at the end of the intervention. Treatment with casein hydrolysate, but not placebo significantly reduced triglycerides and facial pigmentation area. There were significant differences of changes in triglycerides, facial pigmentation area, skin accumulation levels of AGEs, and baPWV between the two groups. Furthermore, changes in triglycerides and skin accumulation levels of AGEs were positively and independently associated with those in facial pigmentation area, whereas changes in baPWV were not. This study suggests that casein hydrolysate reduces facial pigmentation area in nonhypertensive participants partly by decreasing skin accumulation levels of AGEs. Clinical-Trials.gov ID: UMIN000027675.

Investigation and modeling of diurnal variation in suburban ambient formaldehyde concentration.

Formaldehyde (HCHO) is a naturally occurring compound found in ambient air which can induce cancer and sick-building syndrome. It plays an important role in the formation of OH radicals, which are connected to the formation of various airborne chemicals. Herein, we present a simple modeling for the simulation of diurnal variations in the HCHO concentration of ambient air. This was achieved using data collected during different seasons from November 2015 to March 2017 at a suburban location in Toyama City (Japan), where non-methane hydrocarbon (NMHC) levels were low at sub carbon ppm (ppmC) order. The modeling was based on the assumption that photochemical reactions of methane were the major factor of secondary HCHO formation. The model took into account the production and decomposition of HCHO by photochemical reactions as well as its loss due to other reactions such as dry deposition. Accordingly, the model's equation contained terms for solar radiation, temperature, and methane concentration. The results predicted using the model showed good agreement with the experimental data observed on fine days, i.e., except rainy, foggy, and heavily cloudy days. The relationships between HCHO concentration and solar radiation/temperature on different days as well as the seasonal variation of HCHO concentration were also interpreted by the proposed model. This study contributes to the evaluation of the pollution levels of formaldehyde. Moreover, the model may be used to demonstrate the impact of increasing methane levels, with regard to global warming and the background levels of HCHO in the atmosphere.

Population pharmacokinetic and exposure-response analyses of d-amphetamine after administration of lisdexamfetamine dimesylate in Japanese pediatric ADHD patients.

Lisdexamfetamine dimesylate, a prodrug of d-amphetamine, has been approved for treatment of attention-deficit/hyperactivity disorder (ADHD). The purposes of this study were constructing a population pharmacokinetic model of d-amphetamine after dosing of lisdexamfetamine dimesylate and assessing influential factors on the pharmacokinetics of d-amphetamine in Japanese pediatric patients with ADHD. Additionally, the exposure-response relationship was evaluated for Japanese pediatric patients with ADHD using a clinical rating scale, the ADHD Rating Scale IV (ADHD RS-IV, efficacy endpoint) total score as a response index. A total of 1365 points of plasma d-amphetamine concentrations from pediatric patients (6-17 years) with ADHD in clinical studies conducted in Japan and the US were employed for the population pharmacokinetic analysis. The plasma concentrations of d-amphetamine in pediatric patients with ADHD were well described by a one-compartment model with first-order absorption and lag time. The effects of body weight and ethnicity (Japanese or non-Japanese) on apparent total body clearance and the effect of body weight on apparent volume of distribution were incorporated into the final model. No clear exposure-dependent reduction was evident from the ADHD RS-IV total score, whereas the reductions were greater for the lisdexamfetamine dimesylate treatment groups compared with the placebo group regardless of exposure to d-amphetamine.

Pharmacokinetic modeling and simulation for dose rationale of doripenem in neonates and infants.

The aims of this study were to construct a population pharmacokinetic model of doripenem in neonates and infants and to assess the dosing regimen for patients <3 months of age using Monte-Carlo pharmacokinetic/pharmacodynamic (PKPD) simulations. In the population pharmacokinetic analysis using 187 plasma concentrations from 47 neonates and infants, a two-compartment model well described plasma doripenem concentrations with the most significant covariates of chronological age and gestational age identified for the pharmacokinetics of doripenem. Monte-Carlo simulations suggested that the selected dosages for neonates and infants based on chronological age and gestational age (5 or 10 mg/kg) would provide ≥90% target attainment of 40%fT>MIC against MIC of 2 µg/mL in all age groups. These results would be useful for understanding the PKPD characteristics of doripenem, which could provide essential information on optimal therapeutic treatment for neonates and infants.

Population pharmacokinetic and exposure-response analyses of guanfacine in Japanese pediatric ADHD patients.

Guanfacine hydrochloride extended-release tablet (GXR) is approved for child and adolescent patients with attention-deficit/hyperactivity disorder (ADHD). The aims of this study were to develop a population pharmacokinetic model of guanfacine after administration of GXR and to evaluate factors influencing the pharmacokinetics of guanfacine in pediatric ADHD patients. A population pharmacokinetic analysis was performed using 3231 plasma concentration data items of guanfacine for pediatric ADHD patients aged 6-17 years obtained from clinical studies in Japan and the US. In addition, the relationship of the ADHD Rating Scale IV (ADHD RS-IV, efficacy endpoint) total score with exposure to guanfacine was assessed for Japanese pediatric ADHD patients. A one-compartment model with first-order absorption and lag time well described the plasma concentration data of guanfacine in pediatric ADHD patients. Body weight was selected as a covariate of apparent total body clearance and apparent volume of distribution. There was no pharmacokinetic difference between Japanese and non-Japanese pediatric ADHD patients. The results suggested a tendency of exposure-dependent reduction in the ADHD RS-IV total score, whereas the reduction was observed even at low plasma exposure levels compared with the placebo group.

Population Pharmacokinetics of Doripenem in Pediatric Patients and Monte-Carlo Pharmacokinetic-Pharmacodynamic Simulations for Dosing Regimen Assessment.

The aims of this study were to evaluate the pharmacokinetics of doripenem (Finibax®, Doribax®, S-4661), a parenteral carbapenem antibiotic, in pediatric patients based on concentrations of doripenem in plasma after administration of 20 mg/kg 2 or 3 times daily and to evaluate the dosing regimens by using Monte-Carlo pharmacokinetic-pharmacodynamic simulations. Population pharmacokinetic analysis was performed by using 190 plasma concentrations of doripenem from 99 patients (2 months-13 years old). The two-compartment model well described the doripenem plasma concentrations in pediatric patients. Body weight was found to be the most significant influential factor. Gender was also found to be a significant covariate although the effect was relatively small. Monte-Carlo simulations indicated that 20 mg/kg over 1 h infusion would give 90% probability of target attainment for 40% of time above minimum inhibitory concentration against Haemophilus influenzae and Streptococcus pneumoniae, major causative pathogens in pediatric infections, and that 40 mg/kg, the highest approved dose for Japanese pediatric patients, administered over 3 h infusion achieved 98.6% against 8 µg/mL. The developed population pharmacokinetic model of doripenem and Monte-Carlo simulations for pediatric patients should provide useful information for understanding the pharmacokinetic and pharmacokinetic-pharmacodynamic characteristics of doripenem and for optimal treatment of pediatric patients.