Summary: In July 1992, my 24 years of studying abroad in the US as a researcher at Harvard Medical School started. During this period, I met many outstanding scholars who conducted some of the world’s leading research projects. In particular, the opportunity to collaborate with Dr. Jack A. Elias, Professor and Dean Emeritus of the Faculty of Medicine at Brown University, on a project focusing on a molecule called Chitinase 3-like 1 was very helpful to my career, and eventually led to my current position as Professor in charge of international medical exchange at Kurume University School of Medicine. By strengthening the foundation of our exchange programs and actively promoting international joint research projects, I would like to raise the global name recognition of Kurume University.

Summary: Aim: To investigate the natural history of fetal ovarian cysts and elucidate the risk factors for postnatal adverse outcomes in fetal ovarian cysts.

Methods: The study subjects were 18 cases with ovarian cysts prenatally diagnosed using ultrasonography at our hospital between 2007 and 2020. The subjects were classified by cyst characteristics according to echogenic patterns [simple cyst (S) and complex cyst (C)], changes in echogenic patterns (S-to-S, S-to-C, and C-to-C), and diameters (<40 and ≥ 40 mm). Clinical parameters and outcomes were compared between S and C patterns, S-to-S and S-to-C patterns, and <40 and ≥ 40 mm diameters.

Results: Cases with S and C patterns (15 and 3, respectively) had median gestational ages of 35 and 36 weeks, respectively, and maximum cyst diameters of 36 and 57mm, respectively. The number of cases with S-to-S, S-to-C and C-to-C patterns were 11, 4 and 3, respectively. The maximum cyst diameter in cases with S-to-C patterns (58 mm) was larger than that in cases with S-to-S patterns (34 mm) (P<0.05). Placental weight in cases with cysts >40 mm and/or cyst expansion was greater than that in cases with neither or both conditions (P<0.05). Spontaneous resolution (before and after birth) occurred in 8 of 9 and 3 of 9 cases with maximum cyst diameters <40 and ≥ 40 mm, respectively. Ovarian function was lost in 2 cases with S-to-C patterns and in 2 cases with C-to-C patterns.

Conclusion: Cases with cyst diameters ≥ 40 mm and/or cyst expansion during the late third trimester had greater placental weight and more postnatal adverse outcomes.

Summary: Airway stenting involves a stent being inserted into a stenotic site in the airway. In patients with airway stenosis, the airway is the surgical field; therefore, anesthetic management is challenging, and avoiding hypoxia is important. Limited information is available on the anesthetic management of airway stenting. Risk factors for oxygen desaturation during airway stenting remain unknown. The present study was conducted to retrospectively examine patients who underwent airway stenting during a specific period and identify risk factors associated with oxygen desaturation. We performed univariate and multivariate analyses.

The main evaluation items in a multivariate analysis were risk factors for desaturation (SpO₂ ≤ 90%). Body mass index, preoperative orthopnea, the stenotic site of the airway, and severity of stenosis were selected for clinical usefulness.

We analyzed 302 patients who underwent airway stenting at our hospital between July 2011 and June 2014 under general anesthesia with controlled ventilation. Total intravenous anesthesia with propofol target-controlled infusion and remifentanil was performed. Clinical data were extracted from electronic anesthetic records.

The incidence of desaturation (SpO₂ ≤ 90%) was 18.5% (56 out of 302 cases). Preoperative orthopnea (OR, 3.06)and stenosis distal to the bronchus (OR, 3.31) were identified as risk factors for desaturation in a multivariate analysis.

We herein identified risk factors for desaturation during airway stenting. Anesthetic plans need to be carefully considered for patients with these risk factors.

Summary: The purpose of this study was to identify the fundamental roles of visiting nurses as a foundation for creating effective educational programs for nurses of medically dependent (MD) children being treated at home. The relationship among the statements representing 3 types of roles was analyzed using structural equation modeling. There were 296 participants involved in performing home-visit nursing for MD children. Their structural roles related to home-visit nursing systems and skills were strongly correlated with the interpersonal roles related to support for MD children and their families, arrangements for whole families, and interprofessional collaborations. The correlations between these roles and the role determination process demonstrated that their future vision and selfgrowth were weak. This study makes the following recommendations: the development of specialized approaches to nursing practices; training in interprofessional collaboration; the realization of professional self-growth; and the creation of educational programs to assist visiting nurses in improving the home-visit nursing systems.

Summary: Background: Although the therapeutic relationship (or ‘alliance’) is well known to be a key component of psychiatric treatment, there has been no simple way to objectively measure the patient-therapist relationship. Here, we measured the psychological distance between patients and their therapists by using the Pictorial Representation of Illness and Self Measure (PRISM).

Patients and Methods: We analyzed the patient-therapist relationship of 112 patients from two hospitals in Japan (54 males, 57 females, 1 unknown; age 46.20 ± 15.03 years [mean ± SD]) who completed the PRISM and self report questionnaires (LSNS-6, K6, and BASIS-32) about their social network, psychological distress, and outcomes of mental health treatment.

Results: PRISM measurements were available for all patients who consented to participate. In the comparison by disease category, schizophrenia recorded the closest distance to the psychiatrist in charge, followed by bipolar disorder, depression, and neurotic disorder. Regarding the distance to the psychiatrist in charge, PRISM showed a weak negative correlation (r = −0.23, p < 0.05) with age, indicating that with increasing age, the therapeutic rela tionship was more important to the patients.

Conclusion: Our findings indicate the possibility of implementing PRISM to assess the impact of the therapeutic relationship in patients with a wide range of psychiatric disorders, and they suggest that PRISM holds great potential for clinical application.

Summary: Objective: Oxidative damage is observed in the ischemic limbs of patients with arteriosclerosis obliterans. We investigated whether pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, reduced oxidative stress in ischemic limbs and consequently rescued limb damage in model mice.

Materials and Methods: We surgically induced hind-limb ischemia in mice and orally administered pemafibrate solution (P-05 group, 0.5 mg/kg/day; P-10 group, 1.0 mg/kg/day) or control solution (control group). Seven days after the surgery, differences in reactive oxygen species (ROS) contents, antioxidative enzyme and transcription factor expression, blood flow, and capillary density in ischemic limbs were assessed.

Results: Tissue ROS levels were lower in the P-05 and P-10 groups compared with those in the control group. Although the tissue expression levels of nuclear factor-erythroid 2-related factor 2 increased in the P-10 group compared with that in the control group, no corresponding changes were observed in the tissue expression of four antioxidative enzymes. The limb salvage rates and capillary densities in ischemic limbs were higher in the P-05 and P-10 groups than that in the control group.

Conclusion: Pemafibrate treatment reduced oxidative stress and augmented angiogenesis in ischemic limbs, contributing to prevention of limb damage in mice.

Summary: After radical surgery for breast cancer, screening to diagnose recurrence in asymptomatic patients is not recommended. We retrospectively evaluated quality-adjusted survival. Included were fifty-seven recurrent breast cancer patients who died. Survival was partitioned into 3 health states by two different definitions: definition a) time with toxicities due to chemotherapy before progression (TOX1), time from the diagnosis of recurrence to progression without toxicities (TWiST1), and time from progression to death (REL1); definition b) time from the diagnosis of recurrence to death with toxicities (TOX2), without toxicities or hospitalization (TWiST2), and with hospitalization (REL2). Q-TWiST was calculated by multiplying the time in each health state by its utility (uTOX, uTWiST, and uREL). In threshold analyses, uTOX and uREL ranged from 0.0 to 1.0 whereas uTWiST was maintained at 1.0. We compared the patients with (n=32) and without (n=25) symptoms at the time of the diagnosis of recurrence. There was no difference in overall survival after primary surgery, although survival after the diagnosis of recurrence was significantly longer in the asymptomatic patients (p<0.01). Q-TWiST1 and Q-TWiST2 from the diagnosis of recurrence in the asymptomatic patients were significantly longer. Q-TWiST2 from primary surgery in the asymptomatic patients was significantly longer with some combinations of higher uTOX2 and lower uREL2. In conclusion, the asymptomatic detection of recurrence was associated with significantly longer quality-adjusted survival in comparison to symptomatic detection with some combinations of uTOX2 and uREL2. A prospective evaluation would clarify adequate follow-up methods after radical surgery for breast cancer.

Summary: The identification of Aspergillus species has been performed mainly by morphological classification. In recent years, however, the revelation of the existence of cryptic species has required genetic analysis for accurate identification. The purpose of this study was to investigate five Aspergillus section Nigri strains isolated from a patient and the environment in a university hospital. Species identification by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry identified all five black Aspergillus strains as Aspergillus niger. However, calmodulin gene sequence analysis revealed that all five strains were cryptic species, four of which, including the clinical strain, were Aspergillus tubingensis. Hospital-acquired infection of the patient with the A. tubingensis strain introduced from the environment was suspected, but sequencing of six genes from four A. tubingensis strains revealed no environmental strain that completely matched the patient strain. The amount of in vitro biofilm formation of the four examples of the A. tubingensis strain was comparable to that of Aspergillus fumigatus. An extracellular matrix was observed by electron microscopy of the biofilm of the clinical strain. This study suggests that various types of biofilm-forming A. tubingensis exist in the hospital environment and that appropriate environmental management is required.

Summary: Introduction: To investigate the locations of the anterior, middle, and posterior ethmoidal foramina and their relationships to the frontoethmoidal suture.

Methods: One hundred twenty sides from sixty adult human skulls were used. Specimens with significant damage to the medial orbit wall were excluded. The number of ethmoidal foramina (anterior, middle, and posterior) on the medial orbital wall and the relationship of each foramen to the frontoethmoidal suture were recorded and classified as follows: Type I: superior to the frontoethmoidal suture; Type II: on the frontoethmoidal suture; Type III: inferior to the frontoethmoidal suture.

Results: Of the ninety-four sides, fourteen (14.9%) had one foramen, sixty-two (66.0%) had two , and eighteen (19.1%) had three. In total, 192 ethmoidal foramina were observed. Among the fourteen sides with one foramen, eight foramina were anterior and six were posterior. Among the 192 ethmoidal foramina, 162 were eligible for fur ther classification (74 anterior, 14 middle, and 74 posterior). Types I, II, and III ethmoidal foramina were found in 38.3% (62/162), 61.7% (100/162), and 0% (0/162), respectively.

Conclusions: Our current study found a higher incidence of type I than previously reported. It is important to be aware of the significant incidence of foramen variations when the medial orbit wall is manipulated during surgery. Unless caution is observed, an inadvertent surgical injury can occur and lead to life-threatening complications. Therefore, a good understanding of orbital anatomy and its potential variations is critical for improving patient out comes.

Summary: Purpose: Assessment of nutritional status and nutritional interventions is important in gastric cancer patients. We investigated the factors associated with perioperative edema in patients with stage I gastric cancer using a body composition analyzer.

Methods: The study included 106 patients with stage I gastric cancer who underwent distal gastrectomy. The body composition of each patient was evaluated by bioelectrical impedance analysis (BIA) using an InBody 720 body composition analyzer. Patients with an extracellular water to total body water ratio of ≥ 0.4 before and 1 week after gastrectomy were considered to have edema, the cause of which was determined retrospectively.

Results: Patients with preoperative edema were significantly older, had a significantly higher lymph node metastasis rate and disease stage, and had a significantly poorer Controlling Nutritional Status (CONUT) score, and Prognostic Nutritional Index (PNI) compared with patients without preoperative edema. The group with postoperative edema had significantly higher proportions of elderly and female patients as well as a higher rate of Billroth-II reconstruction compared with the group without postoperative edema. The group with postoperative edema also had significantly lower intracellular water content, total body water content, protein content, skeletal muscle mass, and PNI.

Conclusions: Preoperative edema occurs in elderly patients with poor nutritional status, and postoperative edema occurs in elderly patients with a shorter operative time. Perioperative edema status assessed by BIA is thought to be related to perioperative nutritional status.

Summary: To prevent unpleasant symptoms in medical students during systematic anatomy practice, we aimed to develop and validate a model that predicts the likelihood of these symptoms occurring during practice based on risk factors prior to the start of practice. A total of 452 medical students enrolled from 2014 to 2018 were surveyed before and during practice, with questions regarding their sex, psychological status, subjective symptoms, and allergies. The sum of the scores concerning three subjective symptoms related to the eyes and three subjective symptoms related to the nose and fatigue were defined as the “eye-score” and “mask-score,” respectively, and a total score of 7 or more was considered symptomatic. A prediction model was developed based on a generalized linear mixed model; the outcome variable in the model was symptoms during practice, and the explanatory variables were indoor formaldehyde concentration during practice, sex, and pre-practice status, such as the students’ psychological state, eye-score, mask-score, and the presence of allergies. Five-fold cross-validation was used to assess internal validity and the prediction model was applied to 110 medical students enrolled in 2021 to assess external validity. The sensitivity and specificity by five-fold cross-validation were 0.843 and 0.314 for eye symptoms and 0.847 and 0.432 for mask symptoms. In the external validity assessment, the sensitivity and specificity were 0.889 and 0.207 for eye symptoms and 0.879 and 0.532 for mask symptoms. The prediction model developed in this study can be used in future measures aimed at preventing symptoms in students.

Summary: This study investigated the appropriate dose prescription method in static multi-beam stereotactic body radiotherapy for lung tumors. Static multi-beam stereotactic body radiotherapy is a mainstream treatment in Japan. Based on the hypothesis that dose prescription to lower isodose lines may improve planning target volume dose coverage and decrease doses to organs at risk, we investigated changes in dose-volume histograms with prescription to various isodose lines for planning target volume in static multi-beam stereotactic body radiotherapy. In all treatment plans, 45 Gy in 4 fractions were prescribed to 95% of the planning target volume. By adjusting the leaf margins of each beam, various prescription isodose lines encompassing 95% volume of the planning target volume were generated. The prescription isodose lines investigated were 40, 50, 60, 70, 80 and 90% lines relative to the maximum dose of each planning target volume. The conformity index, homogeneity index, mean lung dose, and V5-V40 of the lung were evaluated. The dose was calculated by the adaptive convolve algorithm. The conformity index was lowest in the 70% or 80% isodose plan. The mean lung doses and V10-V40 of the lung decreased steeply from the 90% to the 70% isodose plan, and was lowest in the 60% and 70% isodose plans. These indices increased in the 40% and 50% isodose plans. The optimal stereotactic body radiotherapy plans appeared to be dose prescription to the 60% or 70% isodose line. Further investigation is warranted to clarify the advantage of using this method clinically.

Summary: Purpose: We explored factors affecting gastric emptying in neurologically impaired (NI) patients using the ¹³C-acetate breath test.

Methods: Twenty-four NI patients were classified by the presence of gastroesophageal reflux disease (GERD), which was treated by fundoplication plus gastrostomy, or the absence of GERD, which was treated by gastrostomy alone, along with gastric malposition involving cascade stomach and organoaxial gastric volvulus (OGV). Gastric emptying parameters (GEPs), which were the emptying half time (T _1/2 , minute), the lag phase time (T _lag , minute), and the gastric emptying coefficient (GEC), were measured before and after surgery. We evaluated the relationship between GEPs and GERD, gastric malposition, and surgical intervention. All data were expressed as the median (interquartile range).

Results: The T_1/2 and GEC of patients with OGV were significantly worse than in those without OGV before surgery (T_1/2 with OGV: 241.3 [154.9, 314.3] vs. T_1/2 without OGV: 113.7 [105.2, 151.4], p = 0.01, GEC with OGV: 3.19 [2.46, 3.28] vs. GEC without OGV: 3.65 [3.24, 3.90], p = 0.02). GERD and cascade stomach were not associ ated with GEPs. The GEPs of all NI patients showed no significant difference between before and after surgery. The surgical change in T_1/2 (ΔT _1/2 ) in the patients with OGV was significantly lower than in those without OGV (ΔT_1/2 with OGV: −47.1 [−142.7, −22.1] vs. ΔT_1/2 without OGV: −3.78 [−26.6, 12.0], p = 0.03).

Conclusion: Stomach malposition, such as OGV, seems to affect gastric emptying and may be improved by surgi cal intervention.

Summary: Gastric-type mucinous carcinoma (GAS) of the uterine cervix is the most common adenocarcinoma that develops independently of human papillomavirus infection; it is typically diagnosed at an advanced stage and has a poorer prognosis than usual-type endocervical adenocarcinoma. Few studies have examined the molecular profile of GAS, but genetic alterations in TP53 and STK11 have been repeatedly reported. We analyzed the clinicopathological characteristics and molecular profile of GAS. Fresh-frozen tissue specimens and formalin-fixed paraffin-embedded (FFPE) tissues from 13 patients with GAS treated between January 2000 and December 2020 were analyzed. We performed next-generation sequencing on eight fresh-frozen GAS specimens using the Cancer Hotspot Panel v2 (cases 1–8) and the FoundationOne companion diagnostic (F1CDx) assay on six FFPE samples (cases 8–13). Seventy-four genomic alterations were identified in 42 genes. In order of frequency, TP53, ATRX, CDKN2A, KRAS, APC, and STK11 were altered in at least three cases. Targetable genomic alterations were identified in all six patients’ specimens analyzed using the F1CDx assay. GAS harbors various genomic alterations associated with sustained activation of signaling pathways or cell cycle regulation in addition to abnormalities in TP53, and precision medicine based on molecular profiling will be necessary to overcome GAS.

Summary: Adenoid cystic carcinoma (ACC) is a major histological type of salivary gland cancer but an uncommon form of vulvar cancer. Salivary gland ACC occasionally dedifferentiates into high-grade carcinoma, resulting in poor prognoses. The dedifferentiated component is usually a poorly differentiated cribriform or solid carcinoma, whereas squamous cell carcinoma (SCC) is exceptional. Herein, we report the case of a 78-year-old woman with vulvar ACC, including an SCC component. She presented with a vulvar nodule that had been present for 30 years and increased in size over the past few years. Magnetic resonance imaging showed a ball-like mass with high intensity on T1-weighted images and high intensity with non-uniformity on T2-weighted images. Considering the systemic and social conditions, the tumor was maximally resected without lymphadenectomy. Histologically, the tumor was composed of a marginal ACC component with a central SCC component. Stage IB vulvar cancer, which was assumed to originate from the Bartholin’s gland, was diagnosed. She has survived over 2 years without additional treatments after the surgery. In this case, we assumed that slowly progressive indolent ACC could be dedifferentiated to high- grade SCC. According to our review of available literature, dedifferentiation of vulvar ACC with a high-grade SCC component has not been specifically documented. Although the nature of dedifferentiated vulvar cancer is unclear, it should be noted that high-grade dedifferentiation can occur in long-lasting vulvar masses.

Summary: Background: Until recently, the treatment of spinal muscular atrophy (SMA) was limited to symptomatic treatment with no cure. Three innovative drugs, nusinersen, onasemnogene abeparvovec (OA), and risdiplam have been developed to treat SMA. Although the clinical trials for these drugs have demonstrated their efficacy, there is limited information on real world treatment strategies. In this study, we present a case of a male infant with SMA type 1 who underwent OA treatment after nusinersen treatment.

Case presentation: At 4 months of age, the patient was diagnosed with SMA type 1. At 6 months of age, nusinersen treatment was initiated. His motor function improved, but the effect was limited; therefore, his parents requested gene replacement therapy. During the preparation for OA treatment, anti-adeno-associated virus 9 (AAV9) antibody tests repeatedly showed non-specific reactions, which delayed initiation of treatment. The patient was put on ventilator management after he caught a common cold. During this management, the anti-AAV9 antibody test results were negative. Furthermore, the patient showed increased transaminase levels just before OA treatment; however, since these gradually decreased without signs of liver failure, we started OA treatment at 13 months of age. Four months later, the patient began to sit without support and was weaned from non-invasive positive pressure ventilation, although nasogastric tube feeding remained partially necessary.

Conclusion: We believe that the management of unstable SMA type 1 symptoms, anti-AAV9 antibody testing, and changes in transaminase levels will be helpful for other patients with SMA who require treatment.

Summary: Neurotoxicity associated with cephalosporins is an increasingly recognized complication, although among cephalosporins, ceftazidime is rarely reported for such an adverse reaction. Moreover, subacute, rather than acute, presentation of neurotoxicity associated with cephalosporins is rare.

A 77-year-old female patient with stage 4 chronic renal disease was admitted due to cellulitis in her right lower limb, multiorgan dysfunction complicated by oliguric acute kidney injury, and a need for hemodialysis via a central venous catheter. On the 13th day after admission, she became febrile, and bacteremia associated with a central venous catheter was identified, which prompted the initiation of empirical antibiotic therapy with vancomycin and ceftazidime. After 13 days of antibiotic therapy with vancomycin and ceftazidime, the patient became confused, with temporal-spatial disorientation and myoclonus, especially in the upper limbs, with worsening renal function. Ceftazidime was discontinued, and the patient’s condition improved with complete remission of symptoms on the 8th day after symptom onset.

Neurotoxicity associated with ceftazidime is a rare but probably underdiagnosed adverse reaction. It is more frequent in elderly patients with previous neurological dysfunction and end-stage kidney disease and/or acute kidney injury, and it usually manifests soon after starting treatment. Early identification and monitoring of risk factors and symptoms should lead the physician to a rapid withdrawal of the offending drug.

Summary: Complex breast cysts (CBC) are characterized by a high (up to 31.0%) oncological potential and the need for a biopsy. In some clinical situations, navigating a biopsy using mammography (MG), ultrasound (US), endoscopy, and magnetic resonance imaging (MRI) may be difficult. The first case of stereotaxic core-needle biopsy (sCNB) under pneumocystography (PCG) guide is presented.