Nagoya Journal of Medical Science

Whole-exome and whole-genome sequencing have become widespread in approximately the last 15 years, and the predisposing factors and pathomechanisms of inflammatory keratinization diseases, which have been unknown for a long time, have gradually been revealed. Hence, various inflammatory keratinization diseases are recognized to cause innate immunity hyperactivation. Therefore, we have been advocating for the clinical entity, “autoinflammatory keratinization diseases (AiKDs)” since 2017. AiKDs are inflammatory keratinization diseases caused by autoinflammatory-related pathomechanisms in the skin. The aberrant activation of innate immunity and the resultant autoinflammation in the epidermis and the superficial dermis in AiKDs cause hyperkeratosis in the epidermis. Our initially proposed concept of AiKDs included generalized pustular psoriasis and related conditions, pityriasis rubra pilaris type V, and familial keratosis lichenoides chronica. Since then, the number of diseases known to be AiKDs has increased as previously unknown disease-causing factors and pathogenetic mechanisms of inflammatory keratinization diseases have been clarified one by one. To date, porokeratosis, hidradenitis suppurative, keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK) syndrome, and AiKDs associated with epidermal growth factor receptor (EGFR) deficiency or with hepatitis and autism have been recognized as AiKDs. The concept of AiKDs is considered extremely useful in our precise understanding of the pathogeneses behind inflammatory keratinization diseases and our appropriate treatment method selection. The number of AiKDs is expected to grow with the clarification of the pathomechanisms of further inflammatory keratinization diseases.

We previously reported that spinal cord injury following thoracic endovascular aortic repair for a thoracic aortic aneurysm is a micro embolism caused by a vulnerable mural thrombus. Conversely, patients who underwent thoracic endovascular aortic repair for aortic dissection develop spinal cord injury less frequently due to fewer mural thrombi. Paying attention to preserving blood flow toward the spinal cord, namely collateral circulation and steal phenomenon, prevents spinal cord injury following thoracic endovascular aortic repair for aortic dissection.

Exercise improves physical health and positively impacts physical functions in children. Additionally, the habitual exercise established during childhood often continues into adulthood. Therefore, childhood is an important period for establishing healthy habits. Investigating the relationship between the presence or absence of daily exercise and physical functions may provide important information to confirm poor physical function in children with poor exercise habits. Therefore, this study examined the relationship between exercise habits as defined by the Japanese Ministry of Health, Labor, and Welfare and physical function in children aged 9–12 years. Approximately 239 children were included in this study. Participants answered a questionnaire about their exercise habits. We evaluated the skeletal muscle mass index, grip strength, standing broad jump, one-leg standing time, and gait deviation index. Logistic regression analyses were performed to assess exercise habit association with skeletal muscle mass index, physical function, and gait deviation index after adjusting for sex. Of the 239 children, 75.5% (n = 178) had exercise habits. A significant association was noted between exercise habits and skeletal muscle mass index and standing broad jump (skeletal muscle mass index: OR, 1.84; 95% CI, 1.01–3.36 and p<0.05; standing long jump: OR, 1.02; 95% CI, 1.00–1.04 and p<0.05). In conclusion, exercise regardless of exercise level for at least 30 min per day, 2 days per week, for at least 1 year is important for skeletal muscle mass and instantaneous lower limb muscular strength development in school-aged children.

There are numerous surgical procedures for glaucoma. Minimally invasive glaucoma surgery is becoming popular; however, the disadvantage is the high incidence of anterior chamber hemorrhage. Heavy bleeding can also lead to increased intraocular pressure (IOP) postoperatively. Gonio scratch is a surgical procedure that improves aqueous humor outflow by rubbing off deposits on the trabecular meshwork with a Diamond Dusted Sweeper. As the conjunctiva and trabecular meshwork are not incised, no postoperative bleeding is expected, and the IOP spike will be minimal. We designed this study to determine the efficacy and safety of gonio scratch. This is an on-going multicenter, prospective, clinical trial. Patients who are scheduled for glaucoma surgery with or without cataract surgery are being enrolled. A total of 80 eyes will be recruited in the Hiroshima University Hospital, Miyoshi Eye Clinic, Yokoyama Retina Clinic, and Kusatsu Eye Clinic. All patients will undergo gonio scratch. When combined with cataract surgery, gonio scratch is performed after the intraocular lens is inserted. The primary study endpoint is the change in IOP from baseline to 1 year after surgery. The secondary endpoints are complications, number of glaucoma medications, surgical time, and changes in visual acuity and the visual field. This study protocol was approved by the institutional review board of Hiroshima University. The trial results will be shared with the scientific community at international conferences and by publication in a peer-reviewed journal. Trial registration number is jRCTs062200003.

In Japan, systemic chemotherapy is the standard treatment for unresectable, advanced, or recurrent gastric cancer. However, numerous patients with gastric cancer do not receive late-line treatment because of the rapid progression of gastric cancer. Additionally, late-line treatments, such as nivolumab, trifluridine tipiracil (FTD/TPI), or irinotecan, have limited effects on improving clinical symptoms and delaying the onset of symptoms associated with cancer progression. Recently, a combination of FTD/TPI and ramucirumab was reported to have a high response rate in late-line treatment; however, owing to patient selection bias and a high rate of hematologic toxicity in that previous study, this regimen may not be feasible in real-world clinical applications. Our objective is to conduct a single-arm phase II study to assess the safety and efficacy of FTD/TPI plus ramucirumab combination therapy for gastric cancer after third-line treatment under real-world clinical conditions. This study will recruit 32 patients according to eligibility criteria and administer FTD/TPI (35 mg/m²) and intravenous ramucirumab (8 mg/kg). The primary endpoint will be the time to treatment failure. The secondary endpoints will include the overall survival time, progression-free survival time, overall response rate, disease control rate, relative dose intensity, and incidence of adverse events. The results will add new insights for improving the late-line treatment of advanced gastric cancer.

Many women report postpartum perineal pain due to perineal trauma after vaginal delivery. Perineal pain after giving birth declines over time; however, perineal trauma and pain negatively impact on the women's quality of life and their ability to care for their children. The degree of perineal trauma and instrument delivery with episiotomy are associated with perineal pain. Nevertheless, no studies have examined factors related to postpartum perineal pain, including weight changes during pregnancy as well as the course of delivery so far. We aimed to elucidate obstetric factors associated with perineal pain after vaginal delivery on the first postnatal day in Japanese primiparous women. A cross-sectional study conducted in five maternity hospitals in Japan included 142 primiparous women who vaginally delivered full-term and singleton infants. Perineal pain on the first postnatal day was evaluated using a visual analog scale. The final analysis included 92 participants with a mean age of 30.3 ± 4.6 years. The median visual analog scale score was 54.0 mm. Multiple linear regression analysis demonstrated that gestational weight gain above the recommended Japanese range was positively and significantly associated with perineal pain on the first postnatal day, independent of maternal age, episiotomy, painkiller use, and neonatal birth weight. This finding may provide additional evidence regarding gestational weight gain within the recommended range based on the pre-pregnancy body mass index to reduce perineal pain on the first postnatal day.

The basket-weave method is an orbicularis oris muscle reconstruction method used in primary unilateral cleft lip repair. We compared the long-term results of the basket-weave method with those of a conventional method. For primary unilateral cleft lip repair, we compared the long-term results of 7 cases in which the orbicularis oris muscle was reconstructed by use of the basket-weave method, and of 7 cases in which the reconstruction was performed by use of the conventional method. The average postoperative follow-up period was 12 years and 7 months for the basket-weave method, and 11 years and 9 months for the conventional method. Using photographs of the front and elevation angle views, we evaluated the results as good if the philtrum ridge was formed on the fissure side and was almost symmetrical in height; as fair if the philtrum ridge was lower than the normal side; and as poor if the philtrum ridge had disappeared. For the basket-weave method, the results were good in 6 cases (85.7%), fair in 1 case (14.3%), and poor in 0 cases. For the conventional method, the results were good in 2 cases (28.6%), fair in 4 cases (57.1%), and poor in 1 case (14.3%). A significant difference was found between the 2 groups (Mann-Whitney U test, P = 0.0417). The philtrum ridge shape could be reconstructed by use of the basket-weave method, which gave better results in the long-term than did the conventional method for orbicularis oris muscle reconstruction in primary unilateral cleft lip repair.

The incidence of postoperative nausea and vomiting (PONV) remains high, and improving the accuracy of PONV prediction remains challenging. The primary aim of this study is to examine the impact of anxiety scores evaluated using the Hospital Anxiety and Depression Scale (HADS) on the PONV prediction model. We hypothesized that anxiety and depression, quantified using the HADS, could improve the accuracy of the PONV predictive model. This pilot study evaluated 100 patients. The HADS was conducted by a self-evaluation method before thoracoscopic surgery for lung tumors, and the anesthesia method was standardized. The criterion was whether the nurse in charge of the patient who complained of PONV assessed that drug administration was necessary. As the main analysis, the odds ratio of the HADS score for predicting PONV was evaluated using multivariable logistic regression models. Further, the receiver operating characteristic (ROC) curves of the model with the HADS score added to the variables of without-anxiety predictors and the model with the variables of without-anxiety predictors only were compared. The anxiety score was significantly higher in the PONV group than in the no PONV group (P = 0.021). For predictive accuracy, the model that included age, sex, smoking history, history of PONV, and anxiety score had a higher area under the ROC curve than did the model excluding the anxiety score (P = 0.021). In conclusion, the findings indicate that the HADS is worth investigating as a predictor of PONV.

For patients with moyamoya disease, antiplatelet agents are often used during the perioperative periods of revascularization surgeries to prevent ischemic events. However, antiplatelet therapy is associated with the risk of hemorrhagic complications. Further, the influence of antiplatelet therapy on perioperative ischemic or hemorrhagic complications has not been investigated. This study aimed to determine the impact of antiplatelet agents on adult moyamoya disease patients with ischemic onset during the perioperative period. From January 2016 to December 2020, 183 consecutive combined (direct and indirect) revascularization surgeries for moyamoya disease patients were performed. Among these surgeries, 96 consecutive combined revascularization surgeries for adult moyamoya disease patients with ischemic onset were analyzed and perioperative ischemic and hemorrhagic complications were reviewed. Antiplatelet agents were continued during the perioperative period including on the day of surgery and the day after the surgery. Among 96 surgeries, no hemorrhagic complications occurred postoperatively. Infarction occurred in five cases (5.2%). Among the five cases, neurological deficits persisted in two cases and improved in three. The median value of bleeding volume was 112.5 mL (interquartile range, 80.0 – 200.0). Twenty-five cases (26.0%) needed blood transfusion. The modified Rankin Scale score deteriorated in two cases due to cerebral infarction. The incidence of hemorrhagic and ischemic complications after combined revascularization surgery in patients with ischemic moyamoya disease under antiplatelet therapy was low, indicating the safety of continued antiplatelet therapy.

We compared the relationship between foot alignments and quality of life in patients who underwent initial total knee arthroplasty (TKA). Among the patients with knee osteoarthritis (KOA) who underwent TKA from May 2015 to May 2017 at our hospital, we focused on those in whom weight-bearing foot radiographs had been evaluated preoperatively. The hallux valgus angle and Meary angle were measured by preoperative radiography, and those with hallux valgus angles of 20 degrees or more were classified into the hallux valgus (HV) group, and those with Meary angles of 4 degrees or more into the high arch (HA) group. Also knee and ankle range of motion, knee pain Visual Analog Scale, and the 36-item short-form health survey (SF-36) were measured preoperatively and at discharge, and the amount of these changes was compared in the presence/absence of HV and HA. Regarding HV, there were no significant differences in any of these items between the HV and non-HV groups. However, the SF-physical function was significantly lower in the HA group than in the normal group. In addition, ankle dorsiflexion was lower in the HA group than that in the normal group, although this difference was not statistically significant. There was little improvement of the ankle dorsiflexion, and it was associated with deterioration of the physical function items of SF-36. In total knee arthroplasty patients with HA, physical therapy of the ankles and feet, as well as of the knees, was considered to enhance the improvement of physical function.

Prostaglandin E1 intracavernous injection test is an established method for diagnosing erectile dysfunction. However, the evaluation is non-objective and often influenced by the evaluator’s subjectivity. Herein, we measured and objectively evaluated shear wave elastography results of the corpus cavernosum before and after injection in 16 patients who underwent prostaglandin E1 testing. The response score of prostaglandin E1 tests were “1” in 2 cases, “2” in 2 cases, and “3” in 12 cases. The average transmission velocity before the injection and at the time of maximum erection after the injection were 2.21 m/s and 1.57 m/s, respectively. Transmission velocity decreased during erection in 14 of 16 cases (87.5%). The overall rate of change in transmission velocity due to injection was –26.7% and was significantly different between the poor (responses 1 and 2: –16.1%) and good erection (response 3: –30.2%) groups. To the best of our knowledge, this is the first attempt to evaluate erectile phenomenon using percutaneous ultrasonic elastography in Japan. Rate of change in shear wave transmission velocity due to prostaglandin E1 injection in the corpus cavernosum penis was associated with the degree of erection. Therefore, the rate of change in shear wave transmission velocity in the corpus cavernosum penis could be used as an objective index of erectile phenomenon. Percutaneous ultrasonic elastography is a non-invasive and useful test method for diagnosing erectile dysfunction, determining the therapeutic effect, and predicting prognosis.

Ethical literacy is a critical aspect of professional nursing development. It is considered an essential quality that nursing professionals should possess throughout their careers. Moral sensitivity serves as the foundation for developing ethical literacy. The objective of this study was to develop a reliable tool for assessing moral sensitivity among nursing students. The questionnaire was developed following a rigorous approach, consisting of three stages process, combining the Schwartz-Barcott and Kim hybrid model of concept development with the methodology suggested by Devellis and Waltz. A total of 297 nursing students (287 females, 10 males; mean age: 18.7 years) participated in the study, with five invalid questionnaires excluded from the analysis. The questionnaire’s reliability was established through internal consistency and test-retest reliability analyses. Furthermore, the moral sensitivity questionnaire for nursing students demonstrated satisfactory validity through the results of construct, convergent and discriminant validation procedures. The study findings revealed a significant correlation between the internship performance of students and their overall moral sensitivity score. The questionnaire would be appropriated to be included as a supplemental measure for ethical literacy evaluation.

Family caregivers of terminally ill cancer patients prepare for a patient’s death. Nursing-care for preparedness is effective for their psychological health. This study aims to structuralize nursing-care for preparedness and extract related factors while presenting the implications for improved quality of care. Data from a cross-sectional survey of general ward and palliative care unit nurses in designated cancer care hospitals (n=561) was analyzed with exploratory factor analysis and multiple regression analyses. The results of the analysis, the structure was classified into “Nurse-centered support” and “Support through inter-professional work.” Both supports were practiced significantly more frequently in palliative care units than general wards. Related factors in general wards were; communication skills, cooperation with doctors, the existence of certified nurse/certified nurse specialists as consultants, attitudes toward care of the dying, frequency of death conferences, and cooperation with specialist cancer counselors. Therefore, the results can help improve the quality of family care in palliative care, especially in general wards.

Here we report the case of a 71-year-old woman who complained of lower back and left leg pain due to rod fracture following instrumented fusion using the lateral lumbar interbody fusion and multi-rod technique to treat adult spinal deformity. Radiographic images revealed bilateral rod fractures at L4-5 and pseudoarthrosis at L2-5; lower lumbar lordosis was minimal, but upper lumbar hyperlordosis was noted. The patient underwent revision surgery, which included posterior spinal instrument replacement, L3-4 and L4-5 lateral lumbar interbody fusion cage removal, and L4 vertebral body replacement via the anterior approach. This is a rare case of reoperation with the multi-rod technique. Revision surgery should be performed in consideration of the proportion of lumbar lordosis and anterior bony fusion as the posterior component is resected and bony fusion can only be achieved anteriorly.

Catheter ablation therapy for persistent atrial fibrillation (PeAF) is both difficult and has limited outcomes. The mechanisms underlying the development and persistence of atrial fibrillation (AF) are not fully understood; therefore, ablation strategies are diverse. A 45-year-old man was referred to our hospital for persistent atrial fibrillation to undergo radiofrequency catheter insertion (RFCA). In the first session we conducted pulmonary vein isolation and additional linear ablation, including that of the roof line and posterior inferior line (posterior box lesion) as the stepwise ablation. However, AF was recurred in six months, therefore he was readmitted for second session ablation preoperative 3D computed tomography (CT) scan for drug-refractory PeAF was performed. The additional isolation of the left superior pulmonary vein and potential drivers of AF by mapping wavefront propagation using multipolar catheters by CARTOFINDER (Biosense Webster, Inc, Diamond Bar, CA, USA) was conducted. However, AF did not terminate. Tomography revealed that the left atrial (LA) diverticulum (LAD) was found uniquely. Electrophysiological findings showed focal firing of the myocardial sleeve and LA diverticulum by an approach for defragmented potentials by re-visiting in interval confidence level (ICL) mode included in the electroanatomical mapping system (CARTO 3, Biosense Webster, Inc, Diamond Bar, CA, USA) and the ablation by encircling this site finally made AF terminate. The AF has not recurred for more than 12 months without the use of antiarrhythmic drugs. This case report suggests that additional ablation around substrates in LAD may be effective for treating refractory AF.

The 22q11.2 deletion syndrome has many complications; one of them is immunodeficiency. However, the time of onset and the degree of immunodeficiency can vary. We report a case of a preterm infant with congenital cytomegalovirus infection complicated with 22q11.2 deletion syndrome and immunological abnormalities. Ultrasonography revealed pulmonary atresia, ventricular septal defect, major aortopulmonary collateral artery, and thymic hypoplasia. His serum chemistry tests on admission revealed immunoglobulin G, A, and M levels of 1,547 mg/dL, 70 mg/dL, and 274 mg/dL, respectively. A surface antigen analysis of the peripheral lymphocytes using flow cytometry revealed the following: relatively low CD4-positive T-cell levels (18.1%; 1,767/μL), very high CD8-positive T-cell levels (58.9%; 5,751/μL), and CD4/CD8 ratio of 0.31. The level of T-cell receptor excision circles was relatively low at 17.5 copies/μL. After birth, the CD8-positive T-cell level began to gradually decrease, whereas the CD4/CD8 ratio began to increase. Thrombocytopenia, neutropenia, and skin petechiae were observed on admission. However, the condition improved. Treatment for congenital cytomegalovirus infection was not provided due to the absence of viremia. Unfortunately, the patient died suddenly on the 158th day of life, and the cause of death was unknown. To the best of our knowledge, no association between 22q11 deletion syndrome and cCMV has been described in the recent medical literature. According to the calculation, around one newborn infant who have both 22q11 deletion syndrome and cCMV infection will be born each year in Japan. Healthcare providers should pay more attention to this medical situation in the future.

The radial artery has been used increasingly for percutaneous coronary intervention because of its safety and feasible access route. Nevertheless, transradial complications are possible because of the variation in radial artery anatomy. We experienced a case of the brachioradial artery injury secondary to catheterization, presenting as hypovolemic shock. A 76-year-old woman presented at our emergency department complaining of effort-induced angina. Coronary angiography via the right radial artery showed critical stenosis in the middle of the left anterior descending coronary artery. After wiring into this vessel, balloon angioplasty using a 6-Fr Judkin left guiding catheter was performed with the deployment of the zotarolimus-eluting stent. There was difficulty in negotiating the guidewire and balloons in that resistance was experienced while passing the catheter in the upper arm. Therefore, retrograde radial arteriography was performed to determine any injury to radial artery. This showed contrast extravasation in the brachioradial artery. Initially, manual compression was tried. However, 2 hours later, the patient developed cold sweating and went into a stupor. Laboratory findings showed a decline in hemoglobin, leading to suspicion of hemorrhagic shock. We applied over 30 minutes of balloon inflation, but this was ineffective. While surgical repair was not available, a 6.0 × 50 mm Viabahn stent was placed over the axillary artery. Subsequent angiography showed no further leakage or occlusion of the brachioradial artery. The postprocedural period was uneventful, and the patient was discharged with dual antiplatelet agents. At a 7-year clinical follow-up, the patient was free from limb ischemia symptoms.