Treatment patterns and characteristics of headache in patients in Japan: A retrospective cross-sectional and longitudinal analysis of health insurance claims data.

BACKGROUND: The present study aimed to investigate prescription patterns for patients aged over 17 years with headaches in the REZULT database. METHODS: We conducted a cross-sectional study (Study 1) of the proportion of over-prescription of acute medications (≥30 tablets/90 days for triptans, combination non-steroidal anti-inflammatory drugs (NSAIDs) and multiple types; ≥45 tablets/90 days for single NSAIDs) among patients with headache diagnosed in 2020. We longitudinally studied (Study 2) patients for >2 years from initial headache diagnosis (July 2010 to April 2022). The number of prescribed tablets was counted every 90 days. RESULTS: In Study 1, headache was diagnosed in 200,055 of 3,638,125 (5.5%) patients: 13,651/200,055 (6.8%) received acute medication. Single NSAIDs were prescribed to 12,297/13,651 (90.1%) patients and triptans to 1710/13,651 (12.5%). Over-prescription was found in 2262/13,651 (16.6%) patients and 1200/13,651 (8.8%) patients received prophylactic medication. In Study 2, 408,183/6,840,618 (6.0%) patients were first diagnosed with headaches, which persisted for ≥2 years. Over time, the proportion of patients over-prescribed acute medications increased. Over 2 years, 37,617/408,183 (9.2%) patients were over-prescribed acute medications and 29,313/408,183 (7.2%) patients were prescribed prophylaxis at least once. CONCLUSIONS: According to real-world data, prophylaxis remains poorly prescribed, and both acute and prophylactic treatment rates for headaches have increased over time.

[A Case of Granulocyte Colony-Stimulating Factor-Related Aortitis that Developed during the Treatment of Advanced Prostate Cancer with Neuroendocrine Differentiation].

An 81-year-old man with prostate cancer (cT3aN0M0), who had been undergoing hormonal therapy for 4 years and had maintained low prostate specific antigen levels, developed metastasized pelvic lymph nodes. A tissue biopsy revealed neuroendocrine differentiation of prostate cancer in the metastatic lymph nodes. Consequently, chemotherapy with carboplatin＋etoposide was initiated. During the first course, filgrastim was administered for 2 days due to a drop in his neutrophil count to 230/µl. During the second course, pegfilgrastim was administered as prophylaxis on day 4. However, on day 10 of the second course, he started to develop a fever and fatigue. Suspecting infection, antibiotics were administered, but failed to ameliorate his symptoms. On day 14, plain computed tomography revealed signs of aortic inflammation. Given the lack of improvement even after one week of antibiotic therapy, steroid treatment was initiated on the suspicion of granulocyte colony-stimulating factor (G-CSF) -induced aortitis, which rapidly improved his symptoms. Therefore, when encountering a case in which a fever remains unresponsive to antibiotics during chemotherapy with G-CSF agents, a differential diagnosis of aortic inflammation caused by G-CSF agents needs to be considered.

Myocardial fat accumulation is associated with cardiac dysfunction in patients with type 2 diabetes, especially in elderly or female patients: a retrospective observational study.

BACKGROUND: Ectopic fat is fat that accumulates in or around specific organs or compartments of the body including myocardium. The clinical features of type 2 diabetes patients with high fat accumulation in the myocardium remain unknown. Moreover, little is known about the influence of myocardial fat accumulation in type 2 diabetes on coronary artery disease and cardiac dysfunction. We aimed to clarify the clinical features, including cardiac functions, of type 2 diabetes patients with myocardial fat accumulation. METHODS: We retrospectively enrolled type 2 diabetes patients who underwent ECG-gated coronary computed tomography angiography (CCTA) and abdominal computed tomography (CT) scan examinations within 1 year of CCTA from January 2000 to March 2021. High fat accumulation in the myocardium was defined as the low mean myocardial CT value of three regions of interest, and the associations between CT values and clinical characteristics or cardiac functions were assessed. RESULTS: In total, 124 patients were enrolled (72 males and 52 females). The mean age was 66.6 years, the mean BMI was 26.2 kg/m2, the mean ejection fraction (EF) was 67.6%, and the mean myocardial CT value was 47.7 Hounsfield unit. A significant positive correlation was found between myocardial CT value and EF (r = 0.3644, p = 0.0004). The multiple regression analyses also showed that myocardial CT value was independently associated with EF (estimate, 0.304; 95% confidence interval (CI) 0.092 to 0.517; p = 0.0056). Myocardial CT value showed significant negative correlations with BMI, visceral fat area and subcutaneous fat area (r = - 0.1923, - 0.2654, and -0.3569, respectively, p < 0.05). In patients who were ≥ 65 years or female, myocardial CT value showed significant positive correlations with not only EF (r = 0.3542 and 0.4085, respectively, p < 0.01) but also early lateral annular tissue Doppler velocity (Lat e') (r = 0.5148 and 0.5361, respectively, p < 0.05). The multiple regression analyses showed that myocardial CT value was independently associated with EF and Lat e' in these subgroups (p < 0.05). CONCLUSIONS: Patients with type 2 diabetes, especially in elderly or female patients, who had more myocardial fat had more severe left ventricular systolic and diastolic dysfunctions. Reducing myocardial fat accumulation may be a therapeutic target for type 2 diabetes patients.

Intra-abdominal haemorrhaging after cardiac catheterisation: the importance of recognising vascular anomalies in heterotaxy syndrome.

A 2-month-old boy with a single ventricle underwent cardiac catheterisation. Inferior vena cava angiography at the end of the examination revealed local stenosis, flexion, and connection to the right hepatic vein. Six hours after catheterisation, he went into haemorrhagic shock. CT revealed contrast extravasation into the liver with ascites. A precise diagnosis of vascular anomalies is mandatory, especially in patients with heterotaxy syndrome.

Normal Ventricular and Regional Blood Flow Volumes and Native T1 Values in Healthy Japanese Children Obtained from Comprehensive Cardiovascular Magnetic Resonance Imaging.

Age-related mean and reference ranges for ventricular volumes and mass, regional blood flow measurements, and T1 values using cardiovascular magnetic resonance (CMR) imaging are yet to be established for the pediatric population. Especially in infants and toddlers, no consistent flow volume sets or T1 values have been reported. The purpose of this study was to determine the relevant normal values.Twenty-three children (aged 0.1-15.3 years) without cardiovascular diseases were included. Comprehensive CMR imaging including cine, 2-dimensional phase-contrast, and native T1 mapping, were performed. Ventricular volumes and masses, 11 sets of regional blood flow volumes, and myocardial and liver T1 values were measured. All intraclass correlation coefficient values were > 0.94, except for the right ventricular mass (0.744), myocardial (0.868) and liver T1 values (0.895), reflecting good to excellent agreement between rates.Regression analysis showed an exponential relationship between body surface area (BSA) and ventricular volumes, mass, and regional blood flow volumes (normal value = a*BSAb). Left ventricular myocardial T1 values were regressed on linear regression with age (normal value = -7.39*age + 1091), and hepatic T1 values were regressed on a quadratic function of age (normal value = 0.923*age2 -18.012*age + 613).Comparison of the 2 different methods for the same physical quantities by Bland-Altman plot showed no difference except that the right ventricular stroke volume was 1.5 mL larger than the main pulmonary trunk flow volume.This study provides the normal values for comprehensive CMR imaging in Japanese children.

Ruthenium Complexes Bearing Axially Chiral Bipyridyls: The Mismatched Diastereomer Showed Red Circularly Polarized Phosphorescence.

RutheniumII complexes bearing three axially chiral bipyridyl ligands were synthesized as a new family of chiral complex dyes, and Δ-(S)- and Λ-(S)-diastereomers were obtained. The X-ray crystal structure analyses, spectroscopy, and DFT calculations suggested that all the bipyridyls maintained chirality in both the ground and excited states, and the Δ-(S)- and Λ-(S)-isomers are the matched (more relaxed) and mismatched (more constrained) pairs, respectively. The mismatched Λ-(S)-isomer exhibited red circularly polarized phosphorescence (CPP) both in solution and in the solid state. The solution state CPP is the most intense of ruthenium complexes, while the solid state CPP is the first example of them. It is supposed that, for the Λ-(S)-isomer, the six cumulative CH/π interactions suppress further distortion in the T1 state.

[Spontaneous Resolution of Renal Artery Pseudoaneurysm after Robotic-Assisted Partial Nephrectomy].

Partial nephrectomy (PN) for small renal tumors has become increasingly common. Complications of PN include renal artery pseudoaneurysm (PA), a potentially life-threatening condition. However, the true incidence and natural history of PA after PN remain unclear. Therefore, we conducted a retrospective study of the radiographic characteristics of robotic-assisted partial nephrectomy (RAPN) observed during the postoperative period. We selected 36 consecutive patients with renal carcinoma who underwent RAPN at our institution between December 2016 and May 2019. Patients with contraindications for the use of contrast medium were excluded. A total of 31 eligible patients underwent computed tomography angiography (CTA) during the early postoperative period after RAPN and the incidence of PA was evaluated. Among the patients with PASs, asymptomatic PAs were followed without intervention and their clinical course was assessed using CTA at 1 to 3 months postoperatively. PA was identified in 5 out of 31 (16.1%) patients after RAPN. Median duration between PN and the first CTA was 6 days (range, 1-8). Median PA size was 13 mm (range, 8-17). All (100%) PAs were asymptomatic and resolved spontaneously, as verified by CTA during the late postoperative period. Median duration between identification of PA on early postoperative CTA and subsequent resolution was 92 days (range, 35-106). Our findings indicated that asymptomatic PA after PN can be followed without intervention.

[Needle Lost during Robot-Assisted Laparoscopic Radical Prostatectomy : A Case Report].

A 66-year-old man, who presented with prostate cancer, underwent robot-assisted laparoscopic radical prostatectomy. During surgery, a suture needle was lost after an assistant surgeon removed it from the AirSeal® access port. We were not able to find the needle using a portable radiograph with no contrast optimization. After disassembling the device, the needle was found in the groove of the port top. It should be acknowledged that the needle can become stuck in the AirSeal® port, even though it does not have a valve structure. An X-ray radiograph, with an appropriate gradation setting could be useful to retrieve suture needles.

[A Consideration for the Surgical Approach in Laparoscopic Total Pelvic Exenteration after Radiotherapy : A Case Report].

A 66-year-old woman underwent concurrent chemoradiotherapy (CCRT) for stage IIA cervical cancer. However, two recurrent masses were detected at the vaginal stump 6 years after CCRT, and we performed laparoscopic total pelvic exenteration to obtain a complete cure. Because the terminal ileum appeared white secondary to the effects of radiotherapy, we constructed an ileal conduit using the ileum, approximately 40 cm toward the mouth from the ileocecum. We performed transperineal resection of the vagina and urethra and intersphincteric resection as anal-preservation surgery along with transverse colostomy. We used a right short gracilis myocutaneous flap to reconstruct the pelvic floor and perineum. The operation time was 816 min, and the estimated blood loss was 1,168 ml. On histopathological examination of the resected specimen, the parauterine tissue showed a positive surgical margin. Patients with recurrent cervical cancer after CCRT show poor prognosis. Complete resection with a negative margin is associated with more favorable prognosis in patients with recurrent pelvic masses. Compared with an open procedure, laparoscopic pelvic exenteration is safe and feasible in these patients. Selection of an optimal surgical approach, urinary diversion, and pelvic floor reconstruction is important for complete resection and prevention of perioperative complications.

[Use of Vacuum-Assisted Closure Therapy in the Treatment of Postoperative Inguinal Lymphocele after Lymphadenectomy for a Vulvar Apocrine Adenocarcinoma : A Case Report].

A 79-year-old man with vulvar apocrine adenocarcinoma and right inguinal lymph node metastasis underwent wide excision and free skin graft reconstruction of the primary lesion and right inguinal lymphadenectomy. However, left inguinal lymph node metastasis was noted after 11 months, and left inguinal lymphadenectomy was performed. Twelve days postoperatively, the patient developed left inguinal lymphocele. The lymphocele was drained percutaneously and compressed, but lymph secretion persisted and lymphocele skin necrosis was observed. Therefore, debridement and vacuum-assisted closure (VAC) therapy were performed in cooperation with the department of plastic surgery. Subsequently, lymph secretion declined and eventually stopped. The lymphocele scar was reconstructed with a free skin graft, and after further observation for 8 months, right lymph node swelling was noted. Nevertheless, on the left inguinal site, neither lymphocele recurrence nor inguinal lymph node metastasis was observed. In conclusion, VAC therapy might be beneficial in the treatment of postoperative inguinal lymphocele after lymphadenectomy.

Unexpected Macrocyclic Multinuclear Zinc and Nickel Complexes that Function as Multitasking Catalysts for CO2 Fixations.

Unique self-assembled macrocyclic multinuclear ZnII and NiII complexes with binaphthyl-bipyridyl ligands (L) were synthesized. X-ray analysis revealed that these complexes consisted of an outer ring (Zn3 L3 or Ni3 L3 ) and an inner core (Zn2 or Ni). In the ZnII complex, the inner Zn2 part rotated rapidly inside the outer ring in solution on an NMR timescale. These complexes exhibited dual catalytic activities for CO2 fixations: synthesis of cyclic carbonates from epoxides and CO2 and temperature-switched N-formylation/N-methylation of amines with CO2 and hydrosilane.

[Delay in High-Grade Metastatic Prostate Cancer Progression by Dutasteride : A Case Report].

An 84-year-old man was referred to our hospital with swollen right cervical lymph nodes. Computed tomography showed right supraclavicular and mediastinal lymph node enlargement, and fluorodeoxyglucose positronemissiontomography showed multiple areas of abnormally increased radioactivity inthe right supraclavicular and mediastinal lymph nodes, right ninth rib, and left fifth and seventh ribs. Biopsy of the right supraclavicular lymph node revealed metastatic adenocarcinoma with partial immunohistochemical staining for prostate specific antigen (PSA). Serum PSA levels were not elevated (2.01 ng/ml). An 8-core transrectal prostatic biopsy was negative. Thus, we could not determine the primary site of the adenocarcinoma. The patient was diagnosed with carcinoma of an unknown primary site and followed without chemotherapy. Four years later, he was referred to our hospital due to right hydronephrosis. Serum PSA level was 31. 1 ng/ml. The tumor was not palpable by rectal examination. A 12-core transrectal prostatic biopsy revealed a poorly differentiated adenocarcinoma. Computed tomography revealed metastases in the left axilla, para-aortic, and pelvic lymph nodes as well as in the lung. We diagnosed the patient with prostate cancer, and combined androgen blockade (CAB) was administered. Metastases in the lymph nodes, lung, and bone were reduced on imaging after 1 month of therapy. Therefore, a definitive diagnosis of prostate cancer T1cN1M1c was made. Dutasteride had been administered as a benign prostate hyperplasia treatment 2 years before his first visit, which may have made the definitive diagnosis of prostate cancer difficult. In contrast, dutasteride may have delayed the progressionof prostate cancer inthis patient.

[A Case of Seminal Vesicle Cyst Incidentally Diagnosed during Rupture of Abdominal Subcutaneous Abscess].

Seminal vesicle cyst is a rare disease and is often asymptomatic. We present a case of huge seminal vesicle cyst connected to the abdominal wall and observed as a subcutaneous abscess. An 89-year-old man presented with asymptomatic spontaneous rupture of the left lower abdominal subcutaneous abscess. Computed tomography (CT) showed a relatively low intensity cystic mass located in the Retzius' space just below the abscess, surrounding the right bladder wall laterally and connecting to the right seminal vesicle posteriorly. Biopsy of the skin around the subcutaneous abscess and aspiration biopsy of the pelvic cystic fluid showed no evidence of malignancy. We diagnosed the lesion as a seminal vesicle cyst with bacterial infection. The patient was treated with antibiotics and there has been no relapse.

Polarization imaging camera with a waveplate array fabricated with a femtosecond laser inside silica glass.

In this study, we demonstrate a polarization imaging camera with a waveplate array of a silica glass fabricated by femtosecond (fs) laser direct writing. To use a waveplate array of silica glass for polarization imaging, non-uniformity of the transmittance and retardance in the waveplates must be considered. Therefore, we used a general method of polarization analysis with system matrices determined experimentally for all the units in the waveplate array. We found that a figure of merit based on the determinant of the system matrix could be applied to improve the accuracy of analysis and the robustness to the retardance dispersion for both the simulated and the fabricated waveplate array.

Effective waist circumference reduction rate necessary to avoid the development of type 2 diabetes in Japanese men with abdominal obesity.

The aim of this study was to determine the effective waist circumference (WC) reduction rate in avoiding the development of type 2 diabetes mellitus (T2DM) in <55 years and ≥55 years Japanese men with abdominal obesity. The study subjects were 795 men with WC ≥85 cm, fasting plasma glucose <126 mg/dL, 2-hr plasma glucose on 75 g of oral glucose tolerance test <200 mg/dL, and HbA1c 5.6-6.4 % (38-40 mmol/mol) at baseline who underwent general health checkups more than twice between April 2007 and May 2015. They were divided into 5 groups based on the change in WC during the observation period (WC gain group, and four groups stratified according the rate of WC loss). The subjects were also divided into the <55 years and ≥55 years (at baseline) subgroups. The cumulative incidence rate of T2DM was analyzed and compared among the groups. The cumulative incidence rates of the largest WC loss quartile (≥5.45 %) in all age, of the largest WC loss quartile (≥5.60 %) and second largest WC loss quartile (3.44-5.59 %) in the <55 years subgroup, and of the largest WC loss quartile (≥5.37 %) in the ≥55 years subgroup were significantly lower than that of the gain group (p<0.001, p=0.009, 0.012, and 0.012, respectively). WC reduction rate of at least about 3 % in the younger (<55 years) and at least about 5 % in the older (≥55 years) non-diabetic Japanese men with abdominal obesity can effectively reduce the chance of development of T2DM.

[False Elevation of Prostate-Specific Antigen Caused by Heterophilic Antibody Interference after Radical Prostatectomy : A Case Report].

We described a 63-year-old man who was diagnosed with clinical T1c prostate cancer, with a Gleason score of 6 (3＋3), and a preoperative prostate-specific antigen (PSA) level of 5. 27 ng/ml. Radical prostatectomy(RP) was performed and final pathologyshowed Gleason score 3＋4, pT2c with negative surgical margin. In spite of suggested surgical radicality, PSA was 3.32, 4.78, 5.93 ng/ml, at 1, 2, and 3 months after RP, respectively. However, radiological investigation revealed no metastasis. Because of this clinical discrepancy, we checked the PSA-α1-antichemotrypsin level and found it to be ≦0.1 ng/ml. From these results, false PSA elevation caused byinterference of positive heterophilic antibodies was suggested and demonstrated byseveral immunoassays.

Impact of visceral fat on gene expression profile in peripheral blood cells in obese Japanese subjects.

BACKGROUND: Visceral fat plays a central role in the development of metabolic syndrome and atherosclerotic cardiovascular diseases. The association of visceral fat accumulation with cardio-metabolic diseases has been reported, but the impact of visceral fat on the gene expression profile in peripheral blood cells remains to be determined. The aim of this study was to determine the effects of visceral fat area (VFA) and subcutaneous fat area (SFA) on the gene expression profile in peripheral blood cells of obese subjects. METHODS: All 17 enrolled subjects were hospitalized to receive diet therapy for obesity (defined as body mass index, BMI, greater than 25 kg/m2). VFA and SFA were measured at the umbilical level by computed tomography (CT). Blood samples were subjected to gene expression profile analysis by using SurePrint G3 Human GE Microarray 8 × 60 k ver. 2.0. The correlation between various clinical parameters, including VFA and SFA, and peripheral blood gene expression levels was analyzed. RESULTS: Among the 17 subjects, 12 had normal glucose tolerance or borderline diabetes, and 5 were diagnosed with type 2 diabetes without medications [glycated hemoglobin (HbA1c); 6.3 ± 1.3%]. The mean BMI, VFA, and SFA were 30.0 ± 5.5 kg/m2, 177 ± 67 and 245 ± 131 cm2, respectively. Interestingly, VFA altered the expression of 1354 genes, including up-regulation of 307 and down-regulation of 1047, under the statistical environment that the parametric false discovery rate (FDR) was less than 0.1. However, no significant effects were noted for SFA or BMI. Gene ontology analysis showed higher prevalence of VFA-associated genes than that of SFA-associated genes, among the genes associated with inflammation, oxidative stress, immune response, lipid metabolism, and glucose metabolism. CONCLUSIONS: Accumulation of visceral fat, but not subcutaneous fat, has a significant impact on the gene expression profile in peripheral blood cells in obese Japanese subjects.

Clinical and endocrinological characteristics of adrenal incidentaloma in Osaka region, Japan.

The aim of this study was to investigate the clinical and endocrinological characteristics of adrenal incidentalomas in Osaka region, Japan. The study was a multicenter retrospective analysis of 150 patients with adrenal incidentalomas who underwent radiographic and endocrine evaluations between 2005 and 2013. Most adrenal incidentalomas were discovered by computed tomography (77.0%) and the rest were identified by abdominal ultrasonography (14.6%), magnetic resonance imaging (4.2%), or positron emission tomography (4.2%). Adrenal incidentalomas were more frequently localized on the left side than on the right. The average diameter of tumors was 21 ± 11 mm. On endocrinological evaluation, 14 patients were diagnosed with primary aldosteronism (9.3%), 10 with subclinical Cushing's syndrome (6.7%), 7 with pheochromocytoma (4.7%), 7 with Cushing's syndrome (4.7%), 2 with both subclinical Cushing's syndrome and primary aldosteronism (1.3%), and 110 with non-functioning tumors (73.3%). Patients with functioning tumors were significantly younger and had larger tumor diameters than those with non-functioning tumors. Except for hypertension, complications were comparable between patients with functioning and non-functioning tumors, including the presence of glucose intolerance, cardiovascular disease, and dyslipidemia. In conclusion, a higher prevalence of primary aldosteronism was observed compared with a previous report. Complications were comparable between patients with functioning and non-functioning tumors, including the frequencies of glucose intolerance, cardiovascular disease, and dyslipidemia. Long-term follow-up is required in patients with non-functioning tumors because the frequency of complications, such as glucose intolerance, cardiovascular disease, and dyslipidemia, was equal to that in patients with functioning tumors.

Aminophylline increases respiratory muscle activity during hypercapnia in humans.

BACKGROUND: Theophylline is an old drug traditionally used as a bronchodilator, although it was recently shown to possess anti-inflammatory properties, enhance the actions of corticosteroid actions, and stimulate the respiratory neuronal network. Theophylline has been recognized as an important drug for not only asthma but also corticosteroid-insensitive chronic obstructive pulmonary disease (COPD). To clarify the role of theophylline in hypercapnic ventilatory responses in humans, we analyzed the effects of aminophylline administered at the usual clinical therapeutic doses on ventilation and augmentation of respiratory muscle contractility in room air and under 3 conditions of hypercapnia. STUDY DESIGN: We performed electromyography (EMG) of the parasternal intercostal muscle (PARA) and transversus abdominis muscle (TA) in 7 healthy subjects and recorded both ventilatory parameters and EMG data in room air and under 3 conditions of hypercapnia before (control) and during aminophylline administration. RESULTS: Before aminophylline administration (control), hypercapnic stimulation elicited ventilatory augmentation in a hypercapnia intensity-dependent manner. Ventilatory parameters (tidal volume, frequency of respiration, and minute ventilation) showed significant increases from lower PaCO2 levels during aminophylline administration when compared with the corresponding values before aminophylline administration. EMG activity of both PARA and TA increased significantly at each level of hypercapnia, and those augmentations were shown from lower PaCO2 levels during aminophylline administration. CONCLUSION: Aminophylline administered at the usual clinical therapeutic dose increases ventilation and EMG activity of both inspiratory and expiratory muscles during hypercapnia in healthy humans.