Nagoya Journal of Medical Science最新文献

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.

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.

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.

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.

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.

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.

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.

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.

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.