Chimeric antigen receptor (CAR) is a chimeric molecule consisting of an extracellular antigen recognition domain and an intracellular signal transduction domain. Although the idea about CAR-T cells has been considered for quite some time, it has not been easy to show its efficacy. However, recently developed immunotherapy using CAR-T cells targeting CD19 is rapidly attracting attention because of its remarkable response rate against B-cell malignancies. CAR-T cell therapy has been approved in several countries, and used as standard treatment for relapsed or refractory cases. Under these circumstances, along with immune checkpoint inhibitors, CAR-T cell therapy is now recognized as the fourth treatment option for cancer. On the other hand, it has become clear that CAR-T cell therapy targeting CD19 also has a high relapse rate after complete remission. In addition, the response rate for solid tumors has still been low. One of the reasons for this is known to be exhaustion of CAR-T cells. It is essential to improve the function and characteristics of CAR-T cells in order to improve the response rate of CAR-T therapy and to expand its application to solid tumors. In this paper, the mechanisms of CAR-T cell exhaustion and its contributing factors are summarized. Also, the recent strategies to overcome CAR-T cell exhaustion will be reviewed for developing the next-generation CAR-T cells against solid tumors.

Lipidomics research has accelerated in recent years because of advances in mass spectrometry technology. Imaging mass spectrometry (IMS) is a powerful technique to obtain comprehensive molecular information for identification of lipids and their localization in tissues to explore the underlying pathogenesis of skin diseases, including atopic dermatitis, asteatosis, and ichthyosis. The aim of this study was to compare and perform molecular localization analysis of porcine and human skin lipids by high-resolution matrix assisted laser desorption/ionization (MALDI)-IMS using 9-Aminoacridine (9AA) matrix. 9AA was vapor-deposited onto the thinly sliced skin samples as a matrix to promote ionization of the analyte molecule following laser irradiation. We successfully visualized various skin lipids of both species localized in three different skin layers (stratum corneum, viable epidermis, and dermis) by this method. Molecules with peaks at m/z 465.305, 474.361, and 659.394 were mainly localized in the stratum corneum, those with peaks at m/z 184.076, 273.042, 378.159, 570.228, and 579.228 were localized in the viable epidermis, and those with peaks at m/z 607.361, 615.201, 659.192, 687.545, and 703.571 were localized in the dermis in both species. However, peaks at m/z 465.305 and 659.394 were assigned to cholesterol sulfate and were localized exclusively in the stratum corneum in porcine skin, but abundant in the granular layer in human skin. In conclusion, we performed MALDI-IMS using 9AA matrix and found most of the lipid molecules in porcine and human skin showed similar distributions. However, there were some differences including the localization of cholesterol sulfate.

Patients with severe motor and intellectual disabilities (SMID) have communication challenges, and treatment tends to be late. This study aims to examine the clinical courses of SMID patients who required emergency surgeries and identify key considerations for their management in emergency situations.

Clinical courses of emergency surgeries, examinations and treatments under general anesthesia for SMID from December 2011 to November 2022 were retrospectively examined based on medical records. To evaluate the relationship between elapsed time and clinical course severity, we compared the time from symptom recognition by caregivers to consultation and from consultation to the start of the operation between the groups with and without perioperative complications.

During the study period, a total of 18 emergency surgeries were required for 15 SMID patients, addressing conditions such as bowel obstruction, acute appendicitis, and complications after tracheostomy or gastrostomy. 8 cases presented perioperative complications, 2 of them died perioperatively. The time from symptom recognition by caregivers to consultation was significantly longer in the group with perioperative complications compared to the group without perioperative complications.

In emergency situation of SMID, most of the cases were already advanced at the time of consultation, with longer consultation times increasing the likelihood of perioperative complications. Ensuring prompt and accurate diagnosis of surgical indications is crucial for effective treatment.

Bronchial asthma (BA) is characterized by airway stenosis due to chronic airway inflammation. CYP2R1 is an enzyme primarily responsible for vitamin D metabolism, and some of its single nucleotide polymorphisms (SNPs) have been implicated in BA. Vitamin D binding protein (VDBP) is primarily responsible for vitamin D transport, and some of its SNPs have also been implicated in asthma. Here, we investigated the relationship between serum VDBP, serum 25 (OH) D, and serum calcium, as well as correlations between serum VDBP and laboratory data, in Japanese patients with BA and healthy donors (HDs). We also compared results between genotypes at SNPs of CYP2R1 (rs12794714 and rs10741657) and an SNP of VDBP (rs7041). Serum VDBP levels were significantly higher in the BA group compared with the HD group. Laboratory data did not differ between SNP genotypes in either group. The only parameter significantly correlated with VDBP was serum calcium in both groups. In addition, serum VDBP was correlated with serum calcium in all genotypes in the HD group, but was correlated with only the AA/AG genotype at rs12794714 and rs10741657 and TT/TG genotype at rs7041 in the BA group. Thus, SNP genotypes with an A allele (AA and AG) at rs12794714 and rs10741657 and a T allele (TT and TG) at rs7041, but not the GG genotype, may be involved in the serum VDBP-mediated regulation of serum calcium in BA.

Fumarate hydratase-deficient renal cell carcinoma arises from mutations in the fumarate hydratase (FH) gene, representing a rare subset of renal cell carcinoma (RCC). Approximately 19% of patients formerly diagnosed with type 2 papillary RCCs are FH deficient. FH-deficient RCC typically exhibits an aggressive course and is associated with hereditary leiomyomatosis and RCC syndrome in cases with germline mutations. Herein, we report the case involving a 34-year-old Japanese man who experienced a 20-kg weight loss. Computed tomography identified a left renal tumor, leading to a subsequent left nephrectomy. Pathological analysis confirmed FH-deficient RCC. Following diagnosis, the patient underwent treatment with ipilimumab and nivolumab for liver metastasis. Due to disease progression, cabozantinib was administered as second-line therapy, achieving a partial response. Currently, no established standard therapy exists for FH-deficient RCC. Nevertheless, in this case, the multi-kinase inhibitor cabozantinib was effective in combating resistance to immune checkpoint inhibitors.

The ganglion plexi (GPs) location and vagal response during ablation are not well understood in dextrocardia patients. A 75-year old female with dextrocardia underwent pulmonary vein isolation (PVI) using hot-balloon ablation for atrial fibrillation. A vagal response occurred during the left-superior PV ablation, which was suspected due to neural interactions between the atrial GPs and sinus node. 3D-CT revealed the existence of epicardial adipose tissue (EAT) at the PV antrum and an EAT volume reduction after the PVI. In the present case, the neural location and GP connections consisted of a normal anatomy except for being on the opposite side.

A cluster of COVID-19 outbreaks occurred at a psychiatric institution. The prefectural government ordered Disaster Medical Assistance Team to be dispatched. Patients with moderate disease cannot be transferred to other hospitals, which forces them to support themselves. Although the outside-of-hospital command supporters had zoned from the initial stage, private rooms were limited, and the ward was a mixture of those who had developed the disease and asymptomatic polymerase chain reaction-positive and -negative patients. Only two part-time internists were available to treat the patients, and treating the wards required much work. Unfortunately, no concrete support has been provided by the prefecture's medical association. Measures to support the hospital include adjustments to zoning on a case-by-case basis, reassignment of existing nurses, educational activities on how to wear personal protective equipment, and improving the environment. Additionally, several issues regarding slander existed. To address these various issues, prefectural health and medical coordination headquarters for emerging infectious diseases should be established. Furthermore, guidelines should be provided for ward management strategies, treatment protocols, and staff education in the event of an outbreak of emerging infectious diseases in psychiatric institutions.

Background: Partial anomalous pulmonary venous connection (PAPVC) accounts for 0.4-0.7% of congenital heart disease. Herein, we report a case of successful surgical treatment of PAPVC that preserves the specialized conduction system without any artificial materials.

Case presentation: A 21-year-old male patient had no significant medical history. The patient was referred to our department because the enlargement of right hilar shadow was shown on chest X-ray during a school physical examination. Partial anomalous pulmonary venous connection was diagnosed by contrast enhanced computed tomography. The right upper pulmonary vein was returning to the higher superior vena cava. The pulmonary systemic blood flow ratio was 2.88 on right heart catheterization. Surgery was performed under general anesthesia, with the patient in a supine position. An atrial septum defect was created under cardiac arrest using cardiopulmonary bypass as usual, and the rerouted right upper pulmonary vein blood flow using fresh autologous pericardial patch. An incision was made in the right atrial appendage and sutured to the superior vena cava for creating a pathway for blood flow from the superior vena cava to enter the right atrium (modified Warden procedure).

Postoperative CT scan revealed successful rerouting blood flow of right upper pulmonary vein and superior vena cava.

Superior vena cava-right atrium anastomosis, such as Warden procedure has the advantage of reducing the risk of postoperative sick sinus syndrome because not touching the sinus node. Reconstruction using only autologous tissue has advantages of antithrombogenicity. There are some case reports of an adult patient with using a fresh autologous pericardial patch who developed pulmonary vein obstruction in the remote term. Therefore, careful follow up is necessary in this case.

Conclusions: We performed a successful operation for repair of PAPVC connected to SVC with modified Warden procedure. The procedure was safe and simple and yielded excellent postoperative outcomes.

A patient with lung squamous cell carcinoma, cT4N3M1c (OSS), Stage IVB developed Grade 4 hepatic impairment after 2 cycles of carboplatin + paclitaxel + nivolumab + ipilimumab as first-line chemotherapy. Clinically, an immune-related adverse event (irAE) was suspected and pulse therapy with 1 g methylprednisolone for 3 days was administered twice, followed by prednisolone 100 mg/day and mycophenolate mofetil 2000 mg/day, resolving the hepatic impairment. Immune checkpoint inhibitors can cause severe irAEs, as in the present case where cytotoxic chemotherapy combined with anti-PD-1 and anti-CTLA-4 antibodies caused Grade 4 irAE liver injury, which was successfully treated with steroids and immunosuppressants.

In the absence of distant metastasis after total thyroidectomy for differentiated thyroid cancer, ¹³¹I ablation with a dose of 30 mCi is performed. However, a single dose of ¹³¹I is not always sufficient, and re-dosing is becoming increasingly common. Difficulties are associated with using conventional ¹³¹I whole-body scintigraphy to detect residual thyroid tissue (thyroid bed) in the head and neck region and assess treatment efficacy. Post-treatment imaging with whole-body scintigraphy was performed on the present cases after the first administration of ¹³¹I, and with whole-body scintigraphy and single photon emission computed tomography/computed tomography after the second administration. In case 1, ¹³¹I flowed into the gap between a tooth and crown, and non-specific uptake was observed on single photon emission computed tomography/computed tomography. In case 2, saliva containing ¹³¹I adhered to dentures in the oral cavity, and whole-body scintigraphy indicated uptake in the lesion; however, this was confirmed as a false positive by single photon emission computed tomography/computed tomography. In case 3, the uptake of ¹³¹I in the thyroglossal duct pathway was confirmed by single photon emission computed tomography/computed tomography. Therefore, single photon emission computed tomography/computed tomography was useful for detecting non-specific uptake in the head and neck region.

Pneumoperitoneum and steep Trendelenburg position may cause cerebral abnormalities during robotic-assisted laparoscopic surgery. Previous studies indicated that cerebrovascular autoregulation and the intracranial pressure might be affected by pneumoperitoneum and steep Trendelenburg position. These changes may affect cerebral blood flow, leading to the change of bispectral index (BIS) value. We report a case of a 60-year-old woman who underwent robotic-assisted laparoscopic surgery under general anesthesia, in whom the cause of the decrease in the BIS might be due to pneumoperitoneum and steep Trendelenburg position during surgery. After induction of anesthesia, the BIS value had been stable at 50-60. About 3.5 h after the start of surgery, the BIS started to decrease gradually, and about 5.5 h after surgery, it decreased to around 10-15. The fascial congestion signs (edema of the bulbar conjunctiva and the face, dark red color on the face) were identified. After releasing pneumoperitoneum and deep Trendelenburg position, BIS value increased. Pneumoperitoneum and steep Trendelenburg position may affect the cerebral blood flow and the BIS value, especially during a prolonged surgery. The BIS may be a useful monitor to detect cerebral abnormalities, caused by pneumoperitoneum and steep Trendelenburg position.

The aim of this study is to investigate the long-term effect of oral semaglutide on glycemic control. The effect on glycemic control of switching from a DPP4 inhibitor to oral semaglutide was examined in an extended period of 2 years from baseline in patients (n = 18) from a previous study. Average HbA1c and GA were significantly decreased by oral semaglutide after 2 years compared to baseline. There were no significant differences in each level among measurement time points of 4 months and 1, 1.5 and 2 years. These results show that the effect of oral semaglutide on glycemic control is maintained over a 2-year period.