Is annual screening by fecal immunochemical test necessary after a recent colonoscopy?

Objective: The population-based colorectal cancer screening guidelines in Japan recommend an annual fecal immunochemical test (FIT). However, there is no consensus on the need for annual FIT screening for patients who recently performed a total colonoscopy (TCS). Therefore, we evaluated the repeated TCS results for patients with positive FIT after a recent TCS to assess the necessity of an annual FIT. Methods: We reviewed patients with positive FIT in opportunistic screening from April 2017 to March 2022. The patients were divided into two groups: those who had undergone TCS within the previous 5 years (previous TCS group) and those who had not (non-previous TCS group). We compared the detection rates of advanced neoplasia and colorectal cancer between the two groups. Results: Of 671 patients, 151 had received TCS within 5 years and 520 had not. The detection rates of advanced neoplasia in the previous TCS and non-previous TCS groups were 4.6% and 12.1%, respectively (p < 0.01), and the colorectal cancer detection rates were 0.7% and 1.5%, respectively (no significant difference). The adenoma detection rates were 33.8% in the previous TCS group and 40.0% in the non-previous TCS group (no significant difference). Conclusions: Only a few patients were diagnosed with advanced neoplasia among the patients with FIT positive after a recent TCS. For patients with adenomatous lesions on previous TCS, repeated TCS should be performed according to the surveillance program without an annual FIT. The need for an annual FIT for patients without adenomatous lesions on previous TCS should be prospectively assessed in the future.

Spontaneous migration of a dedicated plastic stent after endoscopic ultrasound-guided hepaticogastrostomy in a patient with surgically altered anatomy: a case report.

Objective: We report a case of spontaneous migration of a dedicated plastic stent after endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) in a patient with surgically altered anatomy. Patient: The patient was a male in his 70s. He underwent EUS-HGS with the successful insertion of a dedicated plastic stent and had no obvious postprocedural complications. However, nine days after the procedure, the patient visited our hospital because of abdominal pain, fever, and stent excretion. We performed EUS-HGS with antegrade stenting, after which the patient had no further complications. Conclusion: Stent migration is considered a complication requiring caution when performing EUS-HGS in patients with surgically altered anatomy.

Japanese orthopaedic association (JOA) clinical practice guidelines on the management of malignant bone tumors - Secondary publication.

BACKGROUND: In Japan, there are currently no general guidelines for the treatment of primary malignant bone tumors. Therefore, the Japanese Orthopaedic Association established a committee to develop guidelines for the appropriate diagnosis and treatment of primary malignant bone tumors for medical professionals in clinical practice. METHODS: The guidelines were developed in accordance with "Minds Clinical Practice Guideline Development Handbook 2014″ and "Minds Clinical Practice Guideline Development Manual 2017". The Japanese Orthopaedic Association's Bone and Soft Tissue Tumor Committee established guideline development and systematic review committees, drawing members from orthopedic specialists leading the diagnosis and treatment of bone and soft tissue tumors. Pediatricians, radiologists, and diagnostic pathologists were added to both committees because of the importance of multidisciplinary treatment. Based on the diagnosis and treatment algorithm for primary malignant bone tumors, important decision-making points were selected, and clinical questions (CQ) were determined. The strength of recommendation was rated on two levels and the strength of evidence was rated on four levels. The recommendations published were selected based on agreement by 70% or more of the voters. RESULTS: The guideline development committee examined the important clinical issues in the clinical algorithm and selected 22 CQs. The systematic review committee reviewed the evidence concerning each CQ and a clinical value judgment was added by experts. Eventually, 25 questions were published and the text of each recommendation was determined. CONCLUSION: Since primary malignant bone tumors are rare, there is a dearth of strong evidence based on randomized controlled trials, and recommendations cannot be applied to all the patients. In clinical practice, appropriate treatment of patients with primary malignant bone tumors should be based on the histopathological diagnosis and degree of progression of each case, using these guidelines as a reference.

Real-Space Visualization of Charged Polymer Network of Hydrogel by Double Network Strategy and Mineral Staining.

Hydrogels consist of three-dimensional (3D) and complicated polymer networks that determine their physical properties. Among the methods for structural analyses of hydrogels, the real-space imaging of a polymer network of hydrogels on a nanometer scale is one of the optimal methods; however, it is highly challenging. In this study, we propose a direct observation method for cationic polymer networks using transmission electron microscopy (TEM). By combining the double network strategy and the mineral staining technique, we overcame the challenges of polymer aggregation and the low electron density of the polymer. An objective cationic network was incorporated into a neutral skeleton network to suppress shrinkage during subsequent staining. Titania mineralization along the cationic polymer strands provided sufficient electron density for the objective polymer network for TEM observation. This observation method enables the visualization of local structures in real space and plays a complementary role to scattering methods for soft matter structure analysis.

Clinical usefulness of endothelial progenitor cells in predicting the efficacy of riociguat in chronic thromboembolic pulmonary hypertension.

Endothelial dysfunction is important in the pathology of pulmonary hypertension, and circulating endothelial progenitor cells (EPCs) have been studied to evaluate endothelial dysfunction. In patients with chronic thromboembolic pulmonary hypertension (CTEPH), riociguat reportedly increases the number of circulating EPCs. However, the relationship between EPC numbers at baseline and changes in clinical parameters after riociguat administration has not been fully elucidated. Here, we evaluated 27 treatment-naïve patients with CTEPH and analyzed the relationships between EPC number at diagnosis and clinical variables (age, hemodynamics, atrial blood gas parameters, brain natriuretic peptide, and exercise tolerance) before and after riociguat initiation. EPCs were defined as CD45dim CD34+ CD133+ cells and measured by flow cytometry. A low number of circulating EPCs at diagnosis was significantly correlated with increased reductions in mean pulmonary arterial pressure (mPAP) (correlation coefficient = 0.535, P = 0.004) and right atrial pressure (correlation coefficient = 0.618, P = 0.001) upon riociguat treatment. We then divided the study population into two groups according to the mPAP change: a weak-response group (a decrease in mPAP of 4 mmHg or less) and a strong-response group (a decrease in mPAP of more than 4 mmHg). The number of EPCs at diagnosis was significantly lower in the strong-response group than in the weak-response group (P = 0.022), but there were no significant differences in other clinical variables or in medication profiles. In conclusion, circulating EPC numbers could be a potential predictor of the therapeutic effect of riociguat in CTEPH patients.

Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease.

Background: Persistent radiological lung abnormalities are evident in many survivors of acute coronavirus disease 2019 (COVID-19). Consolidation and ground glass opacities are interpreted to indicate subacute inflammation whereas reticulation is thought to reflect fibrosis. We sought to identify differences at molecular and cellular level, in the local immunopathology of post-COVID inflammation and fibrosis. Methods: We compared single-cell transcriptomic profiles and T cell receptor (TCR) repertoires of bronchoalveolar cells obtained from convalescent individuals with each radiological pattern, targeting lung segments affected by the predominant abnormality. Results: CD4 central memory T cells and CD8 effector memory T cells were significantly more abundant in those with inflammatory radiology. Clustering of similar TCRs from multiple donors was a striking feature of both phenotypes, consistent with tissue localised antigen-specific immune responses. There was no enrichment for known SARS-CoV-2-reactive TCRs, raising the possibility of T cell-mediated immunopathology driven by failure in immune self-tolerance. Conclusions: Post-COVID radiological inflammation and fibrosis show evidence of shared antigen-specific T cell responses, suggesting a role for therapies targeting T cells in limiting post-COVID lung damage.

Combined Pubic Arch and Ischial Bone Resection for Metachronous and Frequent Local Recurrences of Rectal Cancer.

BACKGROUND/AIM: Complete surgical resection with negative margins remains the cornerstone for curative treatment of rectal cancer; however, local recurrence can pose a significant challenge. Herein, we aimed to introduce a novel surgical technique for combined resection of the pubic arch and ischial bone in the context of treating recurrent rectal cancer. CASE REPORT: We present a case of a patient with a fourth local recurrence of rectal cancer, with no evidence of distant metastasis. The tumor directly invaded the posterior wall of the pubic arch. To achieve complete tumor resection, an osteotomy was performed using a thread wire saw at the bilateral pubic rami and ischial bones. Intraoperative frozen section analysis (rapid tissue examination) was conducted on tissue samples from the lateral margins of the planned osteotomy line. Samples were negative for adenocarcinoma (cancerous cells). The combined resection of the pubic arch and ischial bone was successfully performed with negative margins for adenocarcinoma, as confirmed by frozen section analysis. CONCLUSION: Mastery of the surgical technique for combined resection of the pubic arch and ischial bone may be clinically significant for achieving complete resection in cases of multiple resections for locally recurrent rectal cancer.

Human SARS-CoV-2 challenge uncovers local and systemic response dynamics.

The COVID-19 pandemic is an ongoing global health threat, yet our understanding of the dynamics of early cellular responses to this disease remains limited1. Here in our SARS-CoV-2 human challenge study, we used single-cell multi-omics profiling of nasopharyngeal swabs and blood to temporally resolve abortive, transient and sustained infections in seronegative individuals challenged with pre-Alpha SARS-CoV-2. Our analyses revealed rapid changes in cell-type proportions and dozens of highly dynamic cellular response states in epithelial and immune cells associated with specific time points and infection status. We observed that the interferon response in blood preceded the nasopharyngeal response. Moreover, nasopharyngeal immune infiltration occurred early in samples from individuals with only transient infection and later in samples from individuals with sustained infection. High expression of HLA-DQA2 before inoculation was associated with preventing sustained infection. Ciliated cells showed multiple immune responses and were most permissive for viral replication, whereas nasopharyngeal T cells and macrophages were infected non-productively. We resolved 54 T cell states, including acutely activated T cells that clonally expanded while carrying convergent SARS-CoV-2 motifs. Our new computational pipeline Cell2TCR identifies activated antigen-responding T cells based on a gene expression signature and clusters these into clonotype groups and motifs. Overall, our detailed time series data can serve as a Rosetta stone for epithelial and immune cell responses and reveals early dynamic responses associated with protection against infection.

Synthesis of Substituted 1,2-Dihydroisoquinolines by Palladium-Catalyzed Cascade Cyclization-Coupling of Trisubstituted Allenamides with Arylboronic Acids.

1,2-Dihydroisoquinolines are important compounds due to their biological and medicinal activities, and numerous approaches to their synthesis have been reported. Recently, we reported a facile synthesis of trisubstituted allenamides via N-acetylation followed by DBU-promoted isomerization, where various substituted allenamides were conveniently synthesized from readily available propargylamines with high efficiency. In light of this research background, we focused on the utility of this methodology for the synthesis of substituted 1,2-dihydroisoquinolines. In this study, a palladium-catalyzed cascade cyclization-coupling of trisubstituted allenamides containing a bromoaryl moiety with arylboronic acids is described. When N-acetyl diphenyl-substituted trisubstituted allenamide and phenylboronic acid were treated with 10 mol% of Pd(OAc)2, 20 mol% of P(o-tolyl)3, and 5 equivalents of NaOH in dioxane/H2O (4/1) at 80 °C, the reaction proceeded to afford a substituted 1,2-dihydroisoquinoline. The reaction proceeded via intramolecular cyclization, followed by transmetallation with the arylboronic acid of the resulting allylpalladium intermediate. A variety of highly substituted 1,2-dihydroisoquinolines were concisely obtained using this methodology because the allenamides, as reaction substrates, were prepared from readily available propargylamines in one step.

Prophylactic management of cerebral vasospasm with clazosentan in real clinical practice: a single-center retrospective cohort study.

Introduction: Clazosentan, a selective endothelin receptor subtype A antagonist, reduces vasospasm-related morbidity and all-cause mortality following aneurysmal subarachnoid hemorrhage (SAH) in the Japanese population, as demonstrated by a recent randomized phase 3 trial. However, evidence to suggest clazosentan should be prioritized over the current standard of care to prevent cerebral vasospasm is still lacking. Therefore, we investigated the efficacy and safety of clazosentan in comparison with conventional postoperative management in real-world clinical practice. Methods: We conducted a single-center, retrospective, observational cohort study using prospectively collected data from consecutive patients with aneurysmal SAH. After clazosentan was approved for use in Japan, the conventional postoperative management protocol, composed of intravenous fasudil chloride and oral cilostazol (control group, April 2021 to March 2022), was changed to the clazosentan protocol (clazosentan group, April 2022 to March 2023). The primary endpoint was the incidence of vasospasm-related symptomatic infarction. The secondary endpoints were favorable functional outcomes (modified Rankin scale score < 3) at discharge, angiographic vasospasm, and the need for rescue therapy for delayed cerebral ischemia. Results: The analysis included 100 and 81 patients in the control and clazosentan groups, respectively. The incidence of vasospasm-related symptomatic infarction was significantly lower in the clazosentan group than in the control group (6.2% vs. 16%, p = 0.032). Multiple logistic analyses demonstrated that the use of clazosentan was independently associated with fewer incidence of vasospasm-related symptomatic infarct (23.8% vs. 47.5%, odds ratio 0.34 [0.12-0.97], p = 0.032). Clazosentan was significantly associated with favorable outcomes at discharge (79% vs. 66%, p = 0.037). Moreover, both the incidence of angiographic vasospasm (25.9% vs. 44%, p = 0.013) and the need for rescue therapy (16.1% vs. 34%, p = 0.006) was lower in the clazosentan group. The occurrence of pulmonary edema was significantly higher with clazosentan use (19.8% vs. 5%, p = 0.002), which did not result in morbidity. Conclusion: A postoperative management protocol centering on clazosentan was associated with the reduced vasospasm-related symptomatic infarction and improved clinical outcomes compared to the conventional management protocol in Japanese clinical practice. Clazosentan might be a promising treatment option for counteracting cerebral vasospasm after aneurysmal SAH.

Effects of the COVID-19 pandemic on short-term postoperative outcomes for colorectal perforation: A nationwide study in Japan based on the National Clinical Database.

Aim: Possible negative effects of the COVID-19 pandemic on short-term postoperative outcomes for colorectal perforation in Japan were examined in this study. Methods: The National Clinical Database (NCD) is a large-scale database including more than 95% of surgical cases in Japan. We analyzed 13 107 cases of colorectal perforation from 2019 to 2021. National data were analyzed, and subgroup analyses were conducted for subjects in prefectures with high infection levels (HILs) and metropolitan areas (Tokyo Met. and Osaka Pref.). Postoperative 30-day mortality, surgical mortality, and postoperative complications (Clavien-Dindo grade ≥3) were examined. Months were considered to have significantly high or low mortality or complication rates, if the 95% confidence interval (CI) of the standardized mortality (morbidity) ratio (SMR) does not contain 1. Results: In the NCD, postoperative 30-day mortality occurred in 1371 subjects (10.5%), surgical mortality in 1805 (13.8%), and postoperative complications in 3950 (30.1%). Significantly higher SMRs were found for 30-day mortality in November 2020 (14.6%, 1.39 [95% CI: 1.04-1.83]) and February 2021 (14.6%, 1.48 [95% CI: 1.10-1.96]), and for postoperative complications in June 2020 (37.3%, 1.28 [95% CI: 1.08-1.52]) and November 2020 (36.4%, 1.21 [95% CI: 1.01-1.44]). The SMRs for surgical mortality were not significantly high in any month. In prefectures with HILs and large metropolitan areas, there were few months with significantly higher SMRs. Conclusions: The COVID-19 pandemic had limited negative effects on postoperative outcomes in patients with colorectal perforation. These findings suggest that the emergency system for colorectal perforation in Japan was generally maintained during the pandemic.

High-power and high-efficiency operation of 1.3 µm-wavelength InP-based photonic-crystal surface-emitting lasers with metal reflector.

We demonstrate high-output-power and high-efficiency operation of 1.3-µm-wavelength InP-based photonic-crystal surface-emitting lasers (PCSELs). By introducing a metal reflector and adjusting the phase of the reflected light via optimization of the thickness of the p-InP cladding layer, we successfully achieve an output power of approximately 400 mW with the slope efficiency of 0.4 W/A and the wall-plug efficiency of 20% under CW conditions. In addition, this PCSEL exhibits a narrow circular beam with a divergence angle below 1.6° even at high output powers under CW conditions at temperatures from 15°C to 50°C. We have also demonstrated an output power of over 12 W under pulsed conditions at room temperature.

Age-specific nasal epithelial responses to SARS-CoV-2 infection.

Children infected with SARS-CoV-2 rarely progress to respiratory failure. However, the risk of mortality in infected people over 85 years of age remains high. Here we investigate differences in the cellular landscape and function of paediatric (<12 years), adult (30-50 years) and older adult (>70 years) ex vivo cultured nasal epithelial cells in response to infection with SARS-CoV-2. We show that cell tropism of SARS-CoV-2, and expression of ACE2 and TMPRSS2 in nasal epithelial cell subtypes, differ between age groups. While ciliated cells are viral replication centres across all age groups, a distinct goblet inflammatory subtype emerges in infected paediatric cultures and shows high expression of interferon-stimulated genes and incomplete viral replication. In contrast, older adult cultures infected with SARS-CoV-2 show a proportional increase in basaloid-like cells, which facilitate viral spread and are associated with altered epithelial repair pathways. We confirm age-specific induction of these cell types by integrating data from in vivo COVID-19 studies and validate that our in vitro model recapitulates early epithelial responses to SARS-CoV-2 infection.

Polypharmacy of Older Surgical Patients With Extremity Fractures.

Introduction: Fractures are often caused by falls in older people. Among various causes of falls, polypharmacy is known to be a risk of falls. Furthermore, potentially inappropriate medicines (PIMs), which interact with polypharmacy, include the drugs involved in falls. Here, we primarily aimed to investigate the prescribed drugs in older surgical patients with extremity fractures to determine the frequency of polypharmacy and identify PIMs. The second aim was to clarify the characterization of prescribed drugs of older patients with hip fracture. Materials and Methods: We retrospectively collected the following clinical data of consecutive patients aged ≥65 years who underwent surgery for extremity fractures at our hospital between April 2019 and March 2021. A total of 19 categories were considered as PIMs. The Poisson regression models were used to examine the association between the number of prescribed drugs and hip fracture prevalence. Results: A total of 590 patients were reviewed. Our data showed that 55% of older patients with extremity fractures took ≥6 prescription drugs. The frequency of prescription of hypnotics, antithrombotic drugs, diuretics, and non-steroidal anti-inflammatory drugs was comparatively high among the 19 categories of PIMs. Multivariable analysis revealed that polypharmacy was significantly associated with hip fractures. Among PIMs, antithrombotic drugs and diuretics were significantly associated with the prevalence of hip fractures. Finally, we found a significant positive association between the prevalence of hip fracture and the number of drug categories of PIMs among older patients with extremity fractures. Conclusions: The present study clarified the characterization of the prescribed drugs in older surgical patients with extremity fractures. Special attention should be paid to hip fractures of older patients with polypharmacy or prescribed with many drugs categories of PIMs, particularly antithrombotic drugs and diuretics.

Critical swallowing functions contributing to dysphagia in patients with recurrent laryngeal nerve paralysis after esophagectomy.

BACKGROUND: Recurrent laryngeal nerve paralysis (RLNP) after esophagectomy can cause aspiration because of incomplete glottis closure, leading to pneumonia. However, patients with RLNP often have preserved swallowing function. This study investigated factors that determine swallowing function in patients with RLNP. METHODS: Patients with esophageal cancer who underwent esophagectomy and cervical esophagogastric anastomosis were enrolled between 2017 and 2020. Videofluoroscopic examination of swallowing study (VFSS) and acoustic voice analysis were performed on patients with suspected dysphagia including RLNP. Dysphagia in VFSS was defined as score ≥ 3 of the 8-point penetration-aspiration scale VFSS and acoustic analysis results related to dysphagia were compared between patients with and without RLNP. RESULTS: Among 312 patients who underwent esophagectomy, 74 developed RLNP. The incidence of late-onset pneumonia was significantly higher in the RLNP group than in the non-RLNP (18.9 vs. 8.0%, P = .008). Detailed swallowing function was assessed by VFSS in 84 patients, and patients with RLNP and dysphagia showed significantly shorter maximum diagonal hyoid bone elevation (10.62 vs. 16.75 mm; P = .003), which was a specific finding not seen in patients without RLNP. For acoustic voice analysis, the degree of hoarseness was not closely related to dysphagia. The length of oral intake rehabilitation for patients with and without RLNP was comparable if they did not present with dysphagia (8.5 vs. 9.0 days). CONCLUSIONS: Impaired hyoid bone elevation is a specific dysphagia factor in patients with RLNP, suggesting compensatory epiglottis inversion by hyoid bone elevation is important for incomplete glottis closure caused by RLNP.

A multi-institutional study designed by members of Tokyo Guidelines (TG) Core Meeting to elucidate the clinical characteristics and pathogenesis of acute cholangitis after bilioenteric anastomosis and biliary stent insertion with a focus on biliary obstruction: Role of transient hepatic attenuation difference (THAD) and pneumobilia in improving TG diagnostic performance.

BACKGROUND/PURPOSE: The aim of this study was to clarify the clinical characteristics of acute cholangitis (AC) after bilioenteric anastomosis and stent-related AC in a multi-institutional retrospective study, and validate the TG18 diagnostic performance for various type of cholangitis. METHODS: We retrospectively reviewed 1079 AC patients during 2020, at 16 Tokyo Guidelines 18 (TG 18) Core Meeting institutions. Of these, the post-biliary reconstruction associated AC (PBR-AC), stent-associated AC (S-AC) and common AC (C-AC) were 228, 307, and 544, respectively. The characteristics of each AC were compared, and the TG18 diagnostic performance of each was evaluated. RESULTS: The PBR-AC group showed significantly milder biliary stasis compared to the C-AC group. Using TG18 criteria, definitive diagnosis rate in the PBR-AC group was significantly lower than that in the C-AC group (59.6% vs. 79.6%, p < .001) because of significantly lower prevalence of TG 18 imaging findings and milder bile stasis. In the S-AC group, the bile stasis was also milder, but definitive-diagnostic rate was significantly higher (95.1%) compared to the C-AC group. The incidence of transient hepatic attenuation difference (THAD) and pneumobilia were more frequent in PBR-AC than that in C-AC. The definitive-diagnostic rate of PBR-AC (59.6%-78.1%) and total cohort (79.6%-85.3%) were significantly improved when newly adding these items to TG18 diagnostic imaging findings. CONCLUSIONS: The diagnostic rate of PBR-AC using TG18 is low, but adding THAD and pneumobilia to TG imaging criteria may improve TG diagnostic performance.

Refund: a defense of luck egalitarian policy in healthcare.

Luck egalitarianism assigns a central role to personal responsibility in egalitarian justice. In the context of healthcare, luck egalitarianism is the view that the distribution of medical and healthcare resources-or common resources in general-should respond to the (im)prudence of individuals. Recently, Joar Björk, Gert Helgesson, and Niklas Juth have argued that it is impractical to use luck egalitarianism as a normative framework in healthcare because it has no reasonable way of dealing with the imprudent. In response to their argument, this paper first suggests that the epistemic problems of applying luck egalitarianism to the healthcare context raised by Björk et al. can be circumvented by using the exemption system as a policy application of luck egalitarian healthcare justice. This paper then shows that an ex ante policy, a tax system with refunds, can reasonably be adopted as a luck egalitarian institutional design of healthcare policy. We argue that the proposed conception of luck egalitarianism can deal with the problem of differential option luck. Finally, we show that the threshold problem for the definition of imprudence does not refute the proposed ex ante policy.

Feasibility of accelerated partial breast irradiation with strut-adjusted volume implant brachytherapy in Japan focusing on dosimetry and acute toxicity: a Japanese multi-institutional prospective study.

BACKGROUND: A Japanese multi-institutional prospective study was initiated to investigate the effectiveness and safety of accelerated partial breast irradiation (APBI) using strut-adjusted volume implant (SAVI) brachytherapy, with subjects registered between 2016 and 2021. Herein, we report the preliminary results on the feasibility of this treatment modality in Japan, focusing on the registration process, dosimetry, and acute toxicities. PATIENTS AND METHODS: Primary registration was conducted before breast-conserving surgery (BCS) and the eligibility criteria included the following: age ≥ 40 years, tumor unifocal and unicentric, ≤ 3 cm in diameter, cN0M0, proven ductal, mucinous, tubular, medullary, or lobular carcinoma by needle biopsy. Secondary registration was conducted after BCS had been performed leaving a cavity for device implantation and pathological evaluations, and the eligibility criteria were as follows: negative surgical margin, tumor ≤ 3 cm in diameter on gross pathological examination, histologically confirmed ductal, mucinous, tubular medullary, colloid, or lobular carcinoma, pN0, L0V0, no extensive ductal component, no initiation of chemotherapy within 2 weeks of the brachytherapy APBI planning with SAVI was performed for the patients successfully entered in the study by the secondary registration process, and the treatment was administered at the dose of 34 Gy in 10 fractions administered twice daily. RESULTS: Between 2016 and 2021, 64 women were enrolled in the study through primary registration, of which 19 were excluded from the secondary registration process, and in one, it was deemed impossible to comply with the dose constraints established during treatment planning. After the exclusion of these latter 20 patients, we treated the remaining 44 patients by APBI with SAVI. The dose constraints could be adhered to in all the patients, but re-planning was necessitated in 3 patients because of applicator movement during the treatment period. Grade 2 acute toxicities were observed in 18% of all patients, but more severe acute toxicities than Grade 2 were not observed in any of the patients. CONCLUSION: APBI with SAVI brachytherapy is feasible in Japan from the aspects of compliance with dose constraints and frequency of acute toxicities.

Early prediction of cytokine release syndrome by measuring phosphate and magnesium levels following chimeric antigen receptor T cell therapy.

Introduction: Cytokine release syndrome (CRS) is a life-threatening side effect of chimeric antigen receptor T (CAR-T) cell therapy. This study investigated whether serum inorganic phosphate (IP) and magnesium (Mg) levels are predictive markers of CRS development. Methods: This single-center retrospective cohort study enrolled 16 consecutive patients with diffuse large B-cell lymphoma who had received CAR-T cell therapy. Logistic regression models with generalized estimating equations were used to evaluate whether changes in IP and Mg levels from their baseline values were associated with the development of CRS within 48 hours. Results: Decreased IP and Mg levels from baseline (per 10% change) were associated with an increased CRS incidence (adjusted odds ratio 2.18 [95% confidence interval (CI), 1.31-3.62], 3.18 [95% CI, 1.57-6.44], respectively). Conclusions: Changes in IP and Mg concentrations within 48 hours may be useful predictive markers of CRS onset.