Nagoya Journal of Medical Science

Clinical diagnosis of intraoperative transfusion anaphylaxis using clinical symptoms is challenging and should be made carefully, as an incorrect clinical diagnosis can exacerbate surgical bleeding secondary to stopping a clinically indicated blood transfusion. The timing of onset of anaphylaxis to start of transfusion may be the key to correctly diagnosing intraoperative transfusion anaphylaxis clinically. However, the reliability of this measure remains unknown. A literature search was conducted using MEDLINE, Embase, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials up to June 29, 2021. No language restriction was applied. Two pairs of review authors independently reviewed intraoperative transfusion anaphylaxis cases and extracted data on the timing of onset of anaphylaxis to start of transfusion. A total of 8,918 articles were reviewed, the full texts of 186 articles were assessed, and 20 intraoperative transfusion anaphylaxis cases were included in this study. The 20 intraoperative transfusion anaphylaxis cases included a precise timing of onset. With nine cases, cardiovascular surgery was the most prevalent, and one case was fatal. Fifteen cases had a timing of onset in minutes, and of those, 14 reported timeframes within 30 minutes of initiation of transfusion (median: 15.5, 5–30 minutes). Almost all cases of intraoperative transfusion anaphylaxis occurred within 30 minutes of the transfusion initiation. This timeframe may be helpful in the clinical diagnosis of intraoperative transfusion anaphylaxis.

Despite recent advance in the study of the nature of storage iron turnover, a comprehensive analysis remains lacking. This study aimed to clarify the nature of storage iron turnover. Ferritin-hemosiderin iron transformation rate and the standard normal storage iron turnover rate were utilized in this study to describe the mechanism of iron absorption in relation to ferritin and hemosiderin iron turnover. The synchronization of radioiron uptake peaks by bone marrow and liver indicates that the distribution of radioiron is proportional to the pre-existing iron levels in organs at 24 h after radioiron injection. Moreover, the synchronization indicates the independence of iron mass from red cell precursors in acquiring plasma iron. Thus, the erythron does not dominate the radioiron uptake process. The inverse correlation between transformation rate and the amount of pre-existing iron storage implies that the intra-storage iron turnover is active in iron deficiency, but inactive in iron overload. The decreased ferritin/hemosiderin iron ratio in chronic hepatitis C (CHC) with normal iron storage suggests a trend of iron transformation from ferritin into hemosiderin. The correlation between the pretreatment iron storage and the speed of rebound in CHC implies that the vacant iron-storing rooms in iron-removed cells have a potential to increase iron absorption. This study presents new insights into the turnover of stored iron to enhance our understanding of iron metabolism in various hematologic disorders.

Spontaneous regression of lumbar disc herniation refers to shrinkage or disappearance of herniated nucleus pulposus without invasive surgical treatments. This phenomenon has been reported and is supported by improved clinical symptoms and radiographic after conservative treatment, but the underlying mechanism remains unclear. This article reports 4 cases of disc reabsorption and reviews the distribution of several clinical and radiographic factors of disc herniation reabsorption of total 46 patients, including the four from our study, gathered from 28 recent publications. Some of these factors are present with anomalous distributions. But some factors have similar deviations in patients with lumbar disc herniation. Therefore, more research is needed to explore the correlation between those factors and disc reabsorption.

This study aimed to investigate if our web application could be a viable intervention for providing caregivers with information on resilient coping strategies for the reduction of their burden, thereby leading to the alleviation of behavioural and psychological symptoms of dementia (BPSD). We recruited outpatients with dementia and informal caregiver dyads at Nagoya University Hospital from April 2022 to October 2022. The caregivers were asked to have the web application installed on their smartphones during the study period and answer the following two self-administered questionnaires once a month for 3 months: (a) Abe’s BPSD Score (ABS), which assesses BPSD, and (b) the Japanese version of the Zarit Caregiver Burden Interview (J-ZBI) score, which measures caregiver burden. Thirteen patients and informal caregiver dyads were enrolled in this study. The caregivers exchanged information on the care of patients with dementia in the virtual community using the web application during the study period. Upon entry, J-ZBI scores were correlated with ABSs (r = 0.65). Linear mixed-effects model revealed the average J-ZBI scores decreased over time with significance (p = 0.013), however, the average ABSs did not change during the study period. This is the first study to show that our web application reduces caregiver burden. However, to confirm the efficacy of our web application, further investigations are required.

Traumatic spinal cord injury is characterized by immediate and irreversible tissue loss at the lesion site and secondary tissue damage. Secondary injuries should, in principle, be preventable, although no effective treatment options currently exist for patients with acute spinal cord injury. Traumatized tissues release excessive amounts of adenosine triphosphate and activate the P2X purinoceptor 7/pannexin1 complex, which is associated with secondary injury. We investigated the neuroprotective effects of the blue dye Brilliant Blue FCF, a selective inhibitor of P2X purinoceptor 7/pannexin1 that is approved for use as a food coloring, by comparing it with Brilliant Blue G, a P2X7 purinoceptor antagonist, and carbenoxolone, which attenuates P2X purinoceptor 7/pannexin1 function, in a rat spinal cord injury model. Brilliant Blue FCF administered early after spinal cord injury reduced spinal cord anatomical damage and improved motor recovery without apparent toxicity. Brilliant Blue G had the highest effect on this neurological recovery, with Brilliant Blue FCF and carbenoxolone having comparable improvement. Furthermore, Brilliant Blue FCF administration reduced local astrocytic and microglial activation and neutrophil infiltration, and no differences in these histological effects were observed between compounds. Thus, Brilliant Blue FCF protects spinal cord neurons after spinal cord injury and suppresses local inflammatory responses as well as Brilliant Blue G and carbenoxolone.

Vedolizumab is a treatment option for ulcerative colitis but data on predictors of treatment response remain insufficient to establish personalized treatment strategies. We aimed to investigate the real-world effectiveness of vedolizumab in adult patients with ulcerative colitis and explore factors involved in predicting treatment response. This single-center, single-arm, prospective observational study included 26 patients with clinically active ulcerative colitis patients’ characteristics at baseline, epidemiological information, existing treatment, clinical activity index score, endoscopic score, and blood test data were collected. Serum levels of tumor necrosis factors alpha, interferon gamma, interleukin-4, interleukin-6, interleukin-10, interleukin-17, soluble mucosal addressin cell adhesion molecule 1, and soluble vascular cell adhesion molecule 1 were measured. Patient characteristics in the remission and non-remission groups were compared based on these parameters. Clinical remission at 6 weeks of treatment occurred in 9 (35%) of the 26 patients. At 14 weeks, clinical remission was observed in 11 patients (42%). There were no significant differences pertaining to age, sex, duration of disease, extent of disease, steroid resistance, or prior treatment with biological agents among the two groups after 14 weeks of treatment. Hemoglobin ≥ 11.5 g/dL (odds ratio, 15.0; 95% confidence interval, 1.50–149; P=0.014) and soluble mucosal addressin cell adhesion molecule 1 ≥ 765 pg/mL (odds ratio, 17.3; 95% confidence interval, 2.36–127; P=0.004) were significant factors. In conclusion, hemoglobin and serum soluble mucosal addressin cell adhesion molecule 1 levels are factors correlated with the therapeutic efficacy of vedolizumab.

Body dissatisfaction during pregnancy can significantly impact maternal and child health. Therefore, this longitudinal study investigated changes in body dissatisfaction using two figure rating scales developed from photographic digital data of Japanese pregnant women during the sixth and tenth months of pregnancy. Study participants were recruited at their sixth month prenatal visit at a primary maternity clinic in Japan from October 2014 to March 2015. Body dissatisfaction was estimated based on the perceived and ideal body sizes of 135 pregnant women, expressed as body mass index. Data were collected using self-administered questionnaires. The study found that body dissatisfaction in the tenth month was significantly higher than that in the sixth month. Among the participants, 75 (55.6%) and 79 (58.5%) experienced body dissatisfaction, desiring to be thinner (where perceived body size exceeded ideal body size) during the sixth and tenth months of pregnancy, respectively. Pregnant women who had body dissatisfaction and a desire to be thinner in the sixth month tended to experience an increase in body dissatisfaction by the tenth month compared to those without body dissatisfaction in the sixth month. During the sixth and tenth months, women with body dissatisfaction showed significantly larger perceived body sizes than those without body dissatisfaction. These results indicated that the use of a figure rating scale at the sixth month of pregnancy may help identify women with body dissatisfaction; moreover, perceived body size might be a key factor in preventing an increase in body dissatisfaction from the second to third trimesters.

Neuroectoderm-derived tumors characteristically express gangliosides such as GD3 and GD2. Many studies have reported that gangliosides GD3/GD2 enhance malignant phenotypes of cancers. Recently, we reported that human gliomas expressing GD3/GD2 exhibited enhanced malignant phenotypes. Here, we investigated the function of GD3/GD2 in glioma cells and GD3/GD2-expressing glioma-derived exosomes. As reported previously, transfectant cells of human glioma U251 MG expressing GD3/GD2 showed enhanced cancer phenotypes compared with GD3/GD2-negative controls. When GD3/GD2-negative cells were treated with exosomes secreted from GD3/GD2-positive cells, clearly increased malignant properties were observed. Furthermore, increased phosphorylation of signaling molecules was detected after 5–15 min of exosome treatment, ie, higher tyrosine phosphorylation of platelet-derived growth factor receptor, focal adhesion kinase, and paxillin was found in treated cells than in controls. Phosphorylation of extracellular signal-regulated kinase-1/2 was also enhanced. Consequently, it is suggested that exosomes secreted from GD3/GD2-positive gliomas play important roles in enhancement of the malignant properties of glioma cells, leading to total aggravation of heterogenous cancer tissues, and also in the regulation of tumor microenvironments.

The presence of anti-thyroid antibodies (ATAs) is a biomarker for the development of thyroid dysfunction induced by anti-programmed cell death-1 antibodies (PD-1-Abs). While patients with thyroid dysfunction reportedly showed better overall survival (OS), it remains unknown if ATAs at baseline can predict OS. Therefore, in this study, we examined the association of ATAs at baseline with OS in non-small cell lung cancer (NSCLC) patients with different levels of programmed cell death-1 ligand 1 (PD-L1) positivity associated with PD-1-Ab treatment efficacy. A total of 81 NSCLC patients treated with PD-1-Abs were evaluated for ATAs at baseline and prospectively for OS. Among the 81 patients, 49 and 32 patients had ≥50% (group A) and <50% (group B) PD-L1 positivity, respectively. Median OS did not differ significantly between patients with (n = 13) and without (n = 36) ATAs at baseline in group A. In contrast, median OS was significantly longer in patients with (n = 10) versus without (n = 22) ATAs at baseline in group B (not reached vs 378 days, respectively; 95% CI, 182 to 574 days, p = 0.049). These findings suggest that the presence of ATAs at baseline is a biomarker to predict better treatment efficacy of PD-1-Abs in NSCLC patients with low PD-L1 positivity, while the difference in OS in those with high PD-L1 positivity may be masked by increased tumor expression of PD-L1.

Postoperative air leakage is the most common complication in surgery for malignant lung tumors, leading to extended hospital stays and substantial medical expenses. This study aimed to identify the incidence and characteristics of intraoperative and postoperative air leaks in both robotic-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS), as well as the causes of persistent air leakage following RATS. We conducted a retrospective analysis of patients who underwent lung resection for malignant lung tumors at our institution from October 2018 to August 2022. We compared the incidence rates of intraoperative air leak, postoperative air leak, and persistent air leak between patients who underwent RATS and those who underwent VATS. Background factors were adjusted using propensity score matching. A subanalysis was performed to compare unexpected air leaks, defined as air leaks not observed intraoperatively but confirmed postoperatively. The study included 295 cases of RATS and 227 cases of VATS. In both the overall population and the matched group (187 cases each for RATS and VATS), RATS demonstrated a significantly higher incidence of persistent air leaks compared to VATS (11% vs 3%, p < 0.01; 9% vs 3%, p = 0.02, respectively). RATS also had a significantly higher incidence of unexpected air leaks compared with VATS (29% vs 18%, p = 0.05). Although there was no statistically significant difference in hospital stays, RATS showed a higher incidence of postoperative persistent air leaks and unexpected postoperative air leaks than VATS.

High perioperative mortality and complication rates during the coronavirus disease 2019 (COVID-19) pandemic have been reported. In head and neck reconstruction, not only is patient safety important, but the prevention of infection introduced by the surgical team is also important because the procedure is performed in close proximity to the upper respiratory tract. In addition, recent studies have reported an increased risk for thrombus formation after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 vaccination, which is problematic for microsurgical reconstruction procedures. At the authors’ institution, patients undergoing head and neck reconstruction are requested to stay home for 2 weeks and undergo screening tests for COVID-19 before admission. Surgeons use standard personal protective equipment during surgery. There was no significant difference in the rate of total flap necrosis between the COVID-19 and non-pandemic periods or large difference of perioperative complication rates between vaccinated and non-vaccinated patients. No surgery-related infections among the surgical staff were also found.

This study aimed to share our experience with infants with repaired long-gap esophageal atresia (LGEA) using the native esophagus and Foker and Gazi methods. We retrospectively analyzed the medical records of 10 patients with LGEA (six with pure esophageal atresia [EA], and four with distal trachea-esophageal fistula [TEF] + EA). The mean length between the esophageal pouches was 5.9 cm (4–9 cm). Five Foker methods, three Gazi methods, and two delayed primary repairs after a daily bougie were performed an average of 19.3 days after the first surgery and 26.4 days after the final esophageal anastomosis. For the Foker technique, it was 36.1 days. Their first oral intake was 10.2 days, and their transition to full enteral food was 26.2 days. An esophageal leak was detected in six patients. Fundoplication and dilatations were performed for three and four patients, respectively. For good results, LGEA patients should be operated on at least under the supervision of an experienced surgeon in specialized centers, and the team should be familiar with the techniques for using the native esophagus.

C1-C2 fixation has been developed for the rigid fusion of atlantoaxial instability. C1 lateral mass screw (C1 LMS)-C2 pedicle screw fixation is used more frequently due to its rigid fixation and high bone fusion rate. However, C1 screw placement is relatively unsafe even with recently developed image-based navigation systems. Patient-specific screw guide templates (PSGT) were developed to improve the accuracy and safety of C1 screw placement. Herein, we investigated the outcomes of the C1-C2 posterior fixation technique using PSGT. This was a retrospective study of six patients who underwent posterior cervical spinal fusion using the PSGT between January 2022 and April 2023. Operative time, estimated blood loss, intraoperative radiation dose, surgical cost, and screw placement accuracy were evaluated and compared with those achieved with preoperative CT-based navigation (navigation group, n = 15). Screw accuracy was assessed using Neo’s classification. PSGT showed good results, although the differences were not statistically significant (operation time: 104.3 ± 9.7 min vs 116.4 ± 20.8 min; estimated blood loss: 56.7 ± 72.4 mL vs 123.2 ± 162.3 mL; and radiation dose: 1.8 ± 1.2 mSv vs 2.6 ± 0.8 mSv, respectively). PSGT was particularly better in terms of the accuracy of C1 LMS (PSGT: 100%, navigation: 83.3%). The deviation at the entry point was minimal, and the difference between the sagittal and transversal angles from the preoperative plan was small. We investigated the clinical efficacy of using the PSGT for C1-C2 posterior fixation. PSGT improved the accuracy of C1 LMS insertion.

Head and neck squamous cell carcinoma (HNSCC) has a low five-year survival rate because of its high rate of recurrence and metastasis. After surgical resection or radiation, the main treatments for HNSCC, patients sometimes experience functional or aesthetic disorders. Therefore, there is a great demand for the development of non-surgical treatment strategies to improve clinical outcomes and patients’ quality of life. One such non-surgical treatment is mild hyperthermia (mHT). Many studies have investigated combination treatments with mHT and immune checkpoint inhibitors in preclinical settings. However, there have been no detailed reports on the effects of mHT on immune checkpoint molecules. Here, we investigated the effects of mHT on the tumor microenvironment (TME), particularly on programmed cell death receptor-1 (PD-1)/programmed cell death ligand-1 (PD-L1), in SCCVII cells and a squamous cell carcinoma mouse model. First, we found that PD-L1 mRNA levels and surface PD-L1 expression significantly increased after mHT. Second, a single tumor model was used to determine the effect of HT on the TME. mHT enhanced the accumulation of CD4⁺ and CD8⁺ T cells, elevated PD-L1 expression in the TME, and decreased the PD-1 positive rate of CD4⁺ T cells. Finally, using a bilateral tumor model, we found that anti-PD-L1 monotherapy and combination therapy resulted in longer survival than the isotype control or mHT monotherapy. Moreover, the combination therapy resulted in a significantly higher survival rate than anti-PD-L1 monotherapy. In conclusion, our findings elucidate changes in PD-L1 expression in the TME and strengthen the rationale for mHT and PD-L1 blockade combination therapy.

Blue rubber bleb nevus syndrome (BRBNS) is a rare systemic vascular disorder characterized by multifocal venous malformations (VMs). Little is known about the perinatal management of pregnant women with BRBNS owing to the limited number of reported cases. We present the case of a 36-year-old primigravida with BRBNS who underwent an uneventful cesarean section under spinal anesthesia for breech presentation. A thorough systemic examination revealed VMs in various organs, including the skin, conjunctiva, larynx, gastrointestinal tract, lungs, and vulva. Prior to spinal anesthesia, careful examination using imaging modalities was conducted to assess the spinal and epidural involvement of the VMs to avoid complications, including accidental puncture of the VMs, associated bleeding, and epidural hematoma. In pregnant women with BBNS, it is imperative to scrutinize the localization and distribution of VMs throughout the body to anticipate potential complications and select the appropriate delivery mode and anesthetic management.

We encountered a rare case of appendiceal carcinoma associated with Amyand’s hernia, which was difficult to diagnose preoperatively. A 74-year-old man presented to our hospital with right lower abdominal pain. A hard mass was palpable in the right lower abdomen, and blood tests showed a slightly elevated inflammatory response. Computed tomography revealed a 7 × 5 cm mass with indistinct borders and heterogeneous internal density extending from the cecum to the right lower abdominal wall. We diagnosed appendiceal abscess, however, percutaneous biopsy which was performed for differential diagnosis with appendiceal carcinoma showed no malignancy. Thereafter, the patient was followed up. Two months later, a blood test showed insignificant changes in the inflammatory response and a high serum carcinoembryonic antigen level (48.6 ng/mL). An ultrasound showed a mass contiguous to the appendix, extending to the abdominal wall, with abundant blood flow signals. Fluorodeoxyglucose-positron emission tomography showed a high accumulation of fluorodeoxyglucose in the mass. Four months after the initial visit, the patient had an open ileocecal resection combined with an abdominal wall resection based on the preoperative diagnosis of appendiceal carcinoma invading the abdominal wall. During laparotomy, an enlarged appendix tip extended from the internal inguinal ring outside the inferior epigastric artery to the abdominal wall. Histopathological examination of the appendiceal tumor revealed well-differentiated adenocarcinoma, T4b (abdominal wall), N0, Ly0, and V0. When a right lower abdominal mass extends from the cecum to the abdominal wall, appendiceal tumors associated with Amyand’s hernia should be considered.

This is the first case report of decubitus infection and bacteremia due to Veillonella parvula (V. parvula). A patient in his 70s with pre-existing diabetes mellitus was admitted with decubitus infection, and tazobactam/piperacillin treatment was initiated. Tazobactam/piperacillin-resistant V. parvula was detected in the blood and decubitus site cultures. The antimicrobial treatment was changed to clindamycin and cefmetazole. Antimicrobial therapy was administered for 28 days. The patient was transferred to a convalescent hospital. V. parvula occasionally causes infection in immunocompromised patients with underlying diseases, such as diabetes. An appropriate evaluation by culture test is important for diagnosis, treatment, and recurrence prevention. Tazobactam/piperacillin is often used in the treatment of multi-bacterial infections such as decubitus infections. V. parvula may be resistant to tazobactam/piperacillin, and this possibility should be taken into account when administering treatment.

We encountered the aberrant muscle called transverse carpal muscle (TCM) anterior to the transverse carpal ligament (TCL) during endoscopic carpal tunnel release (ECTR) for a 56-year-old female with left carpal tunnel syndrome (CTS). Our ECTR technique started with making the distal portal and the anomalous muscle emerged in the portal. We changed ECTR to open carpal tunnel release to clarify the anatomy around TCL to avoid iatrogenic tendon and neurovascular injuries. The TCM does not necessarily exist bilaterally, and our case has also it unilaterally, because the TCM was not observed during the ECTR on the opposite side. Distal incision first ECTR technique enabled us to find the TCM which we could not encounter if conventional ECTR was performed.