Search

The increasing occurrence of hospital-associated infections, particularly bacteremia, caused by extensively drug-resistant (XDR) carbapenemase-producing colistin-resistant Klebsiella pneumoniae highlights a critical requirement to discover new therapeutic alternatives. Bacteriophages having host-specific bacteriolytic effects are promising alternatives for combating these pathogens. Among 12 phages isolated from public wastewater in Thailand, two phages-vB_kpnM_05 (myovirus) and vB_kpnP_08 (podovirus) showed broad-host range, producing bacteriolytic activities against 81.3% (n = 26) and 78.1% (n = 25) of 32 XDR carbapenemase-producing colistin-resistant K. pneumoniae, with capsular types-K15, K17, K50, K51, K52/wzi-50 and K2/wzi-2. Both phages showed short replication times, large burst sizes with rapid adsorptions. They exhibited significant stability under various environmental conditions. Genomic analysis revealed that both phages are genetically distinct phages from Myoviridae and Podoviridae family, with the lack of toxin, virulence, lysogeny and antibiotic resistance genes. These characteristics highlighted their promising potential for utilizing in phage therapy for combating XDR K. pneumoniae. Although phage cocktail combining vB_kpnM_05 and vB_kpnP_08 provided significant bacteriolysis for longer duration (8 h) than its monophage (6 h), bacterial regrowth was observed which suggested an evitable development of phage resistance under phages' selection pressures. Future study will be undertaken to elucidate the precise mechanisms by which these XDR K. pneumoniae developed phage resistance and their associated fitness cost. Remarkably, combining phage cocktail with amikacin at their sub-inhibitory concentrations produced potent synergy by completely suppressing bacterial regrowth in vitro. Our study demonstrated the significant therapeutic and prophylactic effectiveness of a phage cocktail-amikacin combination as a promising alternative strategy for overcoming bacteremia associated with XDR K. pneumoniae having carbapenemase and colistin resistance in vivo., Competing Interests: Declaration. Competing interests: The authors declare no competing interests. Informed consent: For this retrospective study of anonymous clinical isolates, the requirement for informed consent from patients was waived by the Institutional Review Board (IRB) of the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand (IRB No.2865/65)., (© 2024. The Author(s).)

Objective: To compare the effects of carbon-ion radiation therapy (CIRT) and external beam radiotherapy (EBRT) on the prognosis of patients with prostate cancer., Methods: The effects of initial prostate-specific antigen (iPSA), clinical Tumor (cT) stage, radiotherapy method, and other clinical factors on the prognosis of 577 patients with radiotherapy were analyzed., Results: Cox regression analysis showed that CIRT (RR: 0.49, p = 0.0215), cT stage ≥ 3 (RR: 2.72, p = 0.0003), and iPSA ≥ 16 ng/mL (RR: 1.74, p = 0.0347) were independent predictors of biochemical recurrence (BCR). After propensity score matching (PSM), CIRT (RR: 0.42, p = 0.0147), cT stage ≥ 3 (RR: 2.55, p = 0.0092), and iPSA ≥ 16 ng/mL (RR: 2.12, p = 0.0366) were still the predictors of univariate analysis. In multivariate analysis, CIRT (RR: 0.42, p = 0.015) and cT stage≥ 3 (RR:2.21, p = 0.0332) were independent predictors of BCR. Among them, we used iPSA and cT stages to establish a new radiotherapy selection model based on BCR risk. Patients who met more than one factor (score ≥ 1) and underwent CIRT had significantly better BCR progression-free survival (PFS) than those who received EBRT (p ≤ 0.01). This was also confirmed by Kaplan-Meier analysis after PSM., Conclusion: CIRT patients exhibited lower 5-year BCR rates compared to the EBRT group. Patients with a risk score of our model ≥ 1 undergoing CIRT were more likely to experience BCR benefits compared to those receiving EBRT., (© 2024 Wiley Periodicals LLC.)

Competing Interests: None.

This fourth edition of the Japanese Clinical Practice Guidelines for Prostate Cancer 2023 is compiled. It was revised under the leadership of the Japanese Urological Association, with members selected from multiple academic societies and related organizations (Japan Radiological Society, Japanese Society for Radiation Oncology, the Department of EBM and guidelines, Japan Council for Quality Health Care (Minds), Japanese Society of Pathology, and the patient group (NPO Prostate Cancer Patients Association)), in accordance with the Minds Manual for Guideline Development (2020 ver. 3.0). The most important feature of this revision is the adoption of systematic reviews (SRs) in determining recommendations for 14 clinical questions (CQs). Qualitative SRs for these questions were conducted, and the final recommendations were made based on the results through the votes of 24 members of the guideline development group. Five algorithms based on these results were also created. Contents not covered by the SRs, which are considered textbook material, have been described in the general statement. In the general statement, a literature search for 14 areas was conducted; then, based on the general statement and CQs of the Japanese Clinical Practice Guidelines for Prostate Cancer 2016, the findings revealed after the 2016 guidelines were mainly described. This article provides an overview of these guidelines., (© 2024 The Japanese Urological Association.)

Purpose: To investigate the usage status of biologics for the chronic treatment of optic neuritis including neuromyelitis optica spectrum disorders in Japan., Design: Multicenter retrospective case series., Methods: Patients diagnosed with anti-aquaporin 4 antibody (AQP4-Ab) positive optic neuritis and had been initiated on biologics (satralizumab, eculizumab, and inebilizumab) between January 2020 and August 2022 were identified at 30 facilities in Japan. These patients were investigated regarding changes in oral steroid doses, optic neuritis relapse, and adverse events after initiation of biologics., Results: Eighty-eight patients with AQP4-Ab positive optic neuritis initiated on biologics were included. Satralizumab was the most common biologic used (79 patients), followed by eculizumab (6 patients) and inebilizumab (3 patients). In the satralizumab group, during the observation period (10.0±7.0 months) until February 2023, the oral steroid dose was reduced significantly from 13.8 ± 8.6 mg/day at the time of initiation to 5.3 ± 4.8 mg/day (p < 0.001). No relapse of optic neuritis was observed in 76 of 79 patients (96.2%) after initiation of satralizumab. Furthermore, in 15 patients who succeeded in discontinuing steroids during 8.5 ± 5.8 months after initiation of satralizumab, no relapse of optic neuritis was observed throughout the observation period. Adverse events occurred in 7 patients with satralizumab and 2 patients with eculizumab, but no serious infections were observed., Conclusions: Satralizumab was the most commonly used biologic for AQP4-Ab positive optic neuritis in Japan. This study demonstrates the efficacy and safety of satralizumab in preventing the relapse of optic neuritis., (© 2024. The Author(s).)

Purpose: This study aimed to evaluate the long-term results of carbon ion radiation therapy (CIRT) for choroidal malignant melanoma (CMM), especially regarding the preservation of the eye and visual acuity (VA)., Methods and Materials: A total of 250 patients with intraocularly localized CMM treated with CIRT between January 2003 and September 2021 were included. The dose prescription included 60 to 85 Gy/4 to 5 fr, with only 68 Gy/4 fr used from 2018 onward. The rotating gantry system with scanning beams was introduced in April 2018. Adverse events (AEs) were graded according to the Common Terminology Criteria for AEs (version 5.0.). For secondary glaucoma, tumor-related visual field defects were excluded from the evaluation. For VA, 245 patients with VA ≥ light perception (LP) were followed up. Effective VA (≥20/200, Snellen equivalent), counting fingers, and LP were used as indicators., Results: The median age was 55 (15-86) years. The T categories 1, 2, 3, and 4 were observed in 16 (6.4%), 41 (16.4%), 189 (75.6%), and 4 (1.6%) patients, respectively. With a median follow-up of 72.5 months, the 5- and 8-year overall survival rates were 87.5% and 84.2%, respectively; the 5- and 8-year local control rates were 94.4% and 92.9%, respectively. At the last follow-up, 19 of 250 patients (7.6%) underwent enucleation, 15 caused by local recurrence and 4 caused by AEs. Secondary glaucoma grades 1, 2, and 3 to 4 were observed in 22 (8.8%), 49 (19.6%), and 5 (2.0%) of patients, respectively. At the last follow-up, ≥ effective VA, ≥ counting fingers, and ≥ LP were maintained in 80 (33%), 120 (49%), and 154 (63%) of patients, respectively. Preservation rate of ≥ LP vision at 5 and 8 years after CIRT was 65.7% and 55.3%, respectively., Conclusions: CIRT for CMM is a promising treatment for both tumor control and preservation of the eye and VA., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: A recent phase I/II study determined the optimal dose of definitive carbon-ion radiotherapy (CIRT) for cT1bN0M0 esophageal cancer. This study aimed to further confirm the efficacy and feasibility of the recommended dose fractionation of CIRT with long-term follow-up results in a larger sample size., Methods: This single center retrospective study evaluated patients with cT1bN0M0 esophageal squamous cell carcinoma treated with the recommended dose fractionation of 50.4 Gy relative biological effectiveness in 12 fractions, between 2012 and 2022., Results: Thirty-eight patients underwent CIRT at our hospital. Although eight (21.1%) patients were older than 80 years, 15 (39.5%) had high surgical risk, and seven (18.4%) were at high risk for chemotherapy, all patients underwent CIRT as scheduled. Grade 3 esophagitis occurred in eight (21.1%) patients and grade 3 pneumonia in one (2.6%) patient in this study, but no grade 4 adverse events occurred. The only grade 3 late adverse event was pneumonia in one patient (2.6%). The 5-year overall survival rate, local control rate, and disease-free survival rates were 76.6% (95% CI, 90.9-62.4), 74.9% (95% CI, 90.7-59.0), and 66.4% (95% CI, 83.3-49.5), respectively. Additionally, post CIRT recurrence was as follows: seven (18.4%) patients had recurrence in another part of the esophagus, three (7.9%) in the primary site, three (7.9%) in lymph nodes outside the irradiated area, and one (2.6%) patient had liver metastasis., Conclusions: Our study demonstrates that CIRT using the recommended dose fractionation is feasible and effective for cT1bN0M0 esophageal squamous cell carcinoma., (© 2024. The Author(s), under exclusive licence to The Author(s) under exclusive licence to The Japan Esophageal Society.)

The real-world benefits of adding androgen-deprivation therapy (ADT) and its optimal duration when combined with current standard high-dose radiation therapy (RT) remain unknown. We aimed to assess the efficacy of and toxicities associated with ADT in the setting of combination with high-dose RT for intermediate-risk (IR) and high-risk (HR) prostate cancer (PCa). This article is a modified and detailed version of the commentary on Clinical Question 8 described in the Japanese Clinical Practice Guidelines for Prostate Cancer (ver. 2023). A qualitative systematic review was performed according to the Minds Guide. All relevant published studies between September 2010 and August 2020, which assessed the outcomes of IR or HR PCa treated with high-dose RT, were screened using two databases (PubMed and ICHUSHI). A total of 41 studies were included in this systematic review, mostly consisting of retrospective studies (N = 34). The evidence basically supports the benefit of adding ADT to high-dose RT to improve tumor control. Regarding IR populations, many studies suggested the existence of a subgroup for which adding ADT had no impact on either overall survival or the BF-free duration. On the other hand, regarding HR populations, several studies suggested the positive impact of adding ADT for ≥1 year on overall survival. Adding ADT increases not only the risk of sexual dysfunction but also that of cardiovascular toxicities or bone fracture. Although the benefit of adding ADT was basically suggested for both IR and HR populations, further investigations are warranted to identify subgroups of patients for whom ADT has no benefit, as well as the appropriate duration of ADT for those who do derive benefit., (© 2024 The Author(s). International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

Background: Proton-based, definitive chemoradiotherapy (P-CRT) for esophageal squamous cell carcinoma (ESCC) previously showed comparable survival outcomes with the surgery-based therapy, i.e., neoadjuvant chemotherapy followed by esophagectomy (NAC-S), in a single-institutional study. This study aimed to validate this message in a Japanese multicenter study., Methods: Eleven Japanese esophageal cancer specialty hospitals have participated. A total of 518 cases with clinical Stage I-IVA ESCC between 2010 and 2019, including 168 P-CRT and 350 NAC-S patients, were enrolled and long-term outcomes were evaluated. Propensity-score weighting analyses with overlap weighting for confounding adjustment were used., Results: The 3-year overall survival (OS) of the P-CRT group was equivalent to the NAC-S group (74.8% vs. 72.7%, hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.61-1.25). Although, the 3-year P-CRT group progression-free survival (PFS) was inferior to the NAC-S group (51.4% vs. 59.6%, HR 1.39, 95% CI 1.04-1.85), the progression P-CRT group cases showed better survival than the NAC-S group (HR 0.58, 95% CI 0.38-0.88), largely because of salvage surgery or endoscopic submucosal dissection for local progression. The survival advantage of P-CRT over NAC-S was more pronounced in the cT1-2 (HR 0.61, 95% CI 0.29-1.26) and cStage I-II (HR 0.50, 95% CI 0.24-1.07) subgroups, although this trend was not evident in other populations, such as cT3-4 and cStage III-IVA., Conclusions: Proton-based CRT for ESCC showed equivalent OS to surgery-based therapy. Especially for patients with cT1-2 and cStage I-II disease, proton-based CRT has the potential to serve as a first-line treatment., (© 2024. The Author(s), under exclusive licence to The Author(s) under exclusive licence to The Japan Esophageal Society.)

Lung cancer has a poor prognosis, and further improvements in outcomes are needed. Radiotherapy plays an important role in the treatment of unresectable lung cancer, and there have been recent developments in the field of radiotherapy for the management of lung cancer. However, to date, there have been few reviews on the improvement in treatment outcomes associated with high precision radiotherapy for lung cancer. Thus, this review aimed to summarize the recent developments in radiotherapy techniques and indicate the future directions in the use of radiotherapy for lung cancer. Stereotactic body radiotherapy (SBRT) for unresectable stage I lung cancer has been reported to improve local control rates without severe adverse events, such as radiation pneumonitis. For locally advanced lung cancer, a combination of chemoradiotherapy and adjuvant immune checkpoint inhibitors dramatically improves treatment outcomes, and intensity-modulated radiotherapy (IMRT) enables safer radiation therapy with less frequent pneumonitis. Particle beam therapy, such as carbon-ion radiotherapy and proton beam therapy, has been administered as advanced medical care for patients with lung cancer. Since 2024, it has been covered under insurance for early stage lung cancer with tumors ≤ 5 cm in size in Japan. In addition to chemotherapy, local ablative radiotherapy improves treatment outcomes in patients with oligometastatic stage IV lung cancer. A particular problem with radiotherapy for lung cancer is that the target location changes with respiratory motion, and various physical methods have been used to control respiratory motion. Recently, coronavirus disease has had a major impact on lung cancer treatment, and cancer treatment during situations, such as the coronavirus pandemic, must be performed carefully. To improve treatment outcomes for lung cancer, it is necessary to fully utilize evolving radiotherapy modalities, and the role of radiotherapy in lung cancer treatment is expected to increase., (© 2024. The Author(s).)

Purpose: To objectively assess visual function in Leber's Hereditary Optic Neuropathy (LHON) patients; this study evaluated pre- and post-idebenone treatment changes in primary visual cortical (V1) responses using functional magnetic resonance imaging (fMRI), given the challenges in subjective testing due to central retinal ganglion cell damage., Study Design: A descriptive study involving four confirmed LHON patients., Methods: Four patients received 900 mg/day of oral idebenone for 24 weeks. Baseline and post-treatment visual acuity, visual fields, and BOLD fMRI responses while passively viewed drifting contrast pattern visual stimuli were compared with self-reported symptoms., Results: Post-idebenone, one patient showed positive trends across subjective tests, reported symptoms, and fMRI. Two patients had stable symptoms and fMRI responses; one improved on subjective tests, and another worsened slightly. Another patient improved in visual field tests despite worsening symptoms and fMRI trends., Conclusion: fMRI may offer a valuable objective measure of visual functions in LHON and appears to be more relevant in assessing symptoms. Further research with more participants is needed to ascertain fMRI's role in developing objective visual assessments and treatment evaluation., (© 2024. Japanese Ophthalmological Society.)

Background and Purpose: To investigate the toxicity and survival outcomes of proton and carbon ion radiotherapy for patients with operable early-stage lung cancer who are eligible for lobectomy., Materials and Methods: This multicenter nationwide prospective cohort study included patients with operable early-stage lung cancer. Proton and carbon ion radiotherapy was performed according to the schedule stipulated in the unified treatment policy. Progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were evaluated., Results: A total of 274 patients were enrolled and included in efficacy and safety analyses. The most common tumor type was adenocarcinoma (44 %), while 105 cases (38 %) were not histologically confirmed or diagnosed clinically. Overall, 250 (91 %) of the 274 patients had tumors that were peripherally situated, while 138 (50 %) and 136 (50 %) patients were treated by proton and carbon ion radiotherapy, respectively. The median follow-up time for all censored patients was 42.8 months (IQR 36.7-49.0). Grade 3 or severe treatment-related toxicity was observed in 4 cases (1.5 %). Three-year PFS was 80.5 % (95 % CI: 75.7 %-85.5 %) and OS was 92.5 % (95 % CI: 89.3 %-95.8 %). Pathological confirmation and clinical stage were factors significantly associated with PFS, while tumor location and particle-ion type were not. Meanwhile, clinical stage was significantly associated with OS, but pathological confirmation, tumor location, and particle-ion type were not., Conclusions: Particle therapy for operable early-stage lung cancer resulted in excellent 3-year OS and PFS in each subset. In this disease context, proton and carbon ion beam therapies are feasible alternatives to curative surgery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that would directly affect the research reported in this paper. Hideyuki Harada received Honoraria from Astrazeneca, Accuray, Chugai pharmaceutical, Takeda pharmaceutical, MSD, Eizai pharmaceutical, Phizer, Brainlab, Hitachi, Novartis, Guerbet Japan, GE Healthcare, Nihon Medi-Physics and Taiho pharmaceutical outside this work. Keita Mori received Honoraria from Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, Daiichi-Sankyo and Eli Lilly Japan outside this work. Hitoshi Ishikawa received Honoraria from Boston Scientific Corporation and MSD outside this work. Masaki Nakamura received Honoraria from Astrazeneca outside this work. Nobuteru Kubo received Honoraria from Astrazeneca outside this work. Miyako Satouchi received Honoraria from Chugai pharmaceutical, Astrazeneca,Eli Lilly Japan, Ono pharmaceutical, Bristol-Myers Squibb, MSD, Merck Janssen Pharmaceutical, Amgen, Taiho pharmaceutical, Pfizer, Daiichi-Sankyo, Eisai, Takeda pharmaceutical, Novartis, GlaxoSmithKline Consumer Healthcare Japan and Bayer pharmaceutical and research funding from GlaxoSmithKline, AstraZeneca, MSD, Janssen, Amgen, Taiho pharmaceutical, Ono pharmaceutical, Bristol Myers Squibb, Pfizer, Daiichi-Sankyo, and Eisai outside this work. Yoshiyuki Shioyama received Honoraria from Astrazeneca outside this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Salvage radical prostatectomy is a postradiation treatment for patients with localized prostate cancer. In 2016, Ozu et al. (Ozu C, Aoki K, Nakamura K, Yagi Y, Muro Y, Nishiyama T, et al. The initial case report: salvage robotic assisted radical prostatectomy after heavy ion radiotherapy. Urol Case Rep 2016; 7 :45-7) first reported salvage robotic-assisted radical prostatectomy (sRARP) after heavy-ion radiotherapy (HIRT). Thereafter, sRARP has been performed in >100 cases. However, it is currently avoided owing to some difficulties. Herein, we report about sRARP in a 67-year-old man who received two sessions of HIRT despite some expected challenges. He was initially treated with HIRT for prostate cancer in 2009 and received the second HIRT as salvage treatment for local recurrence in 2016. In 2019, he had biochemical recurrence and underwent sRARP. There were no significant peri- or postoperative complications. Subsequently, 12 months after sRARP, hormonal therapy was introduced after the diagnosis of biochemical recurrence. The patient's prostate-specific antigen level is currently undetectable., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

A conjunctival cyst is a rare yet significant complication following strabismus surgery. This report describes a nine-year-old girl who developed a conjunctival cyst after undergoing bilateral lateral rectus recession surgery for intermittent exotropia. Despite an uneventful surgery and standard postoperative care, she presented with a gradually enlarging subconjunctival mass in the left eye three months later. Initial conservative treatment with topical antibiotics and steroids proved ineffective, leading to surgical excision six months postoperatively. Histopathological examination confirmed the cyst as a conjunctival epithelial inclusion cyst, characterized by cuboidal epithelium containing goblet cells. The patient's postoperative course was uneventful, with no recurrence of the cyst at six months follow-up, stable visual acuity, and maintained strabismus correction. In managing this case, two crucial lessons were learned. Firstly, the need for precise surgical techniques and the use of adequate pre- and intraoperative disinfection measures to prevent postoperative complications. Ensuring that the conjunctival tissue is not inadvertently included in the wound closure and maintaining a sterile environment throughout the surgery are critical steps. Secondly, the importance of early recognition and timely intervention for postoperative complications. The patient's cyst developed three months post-surgery and did not respond to conservative treatments, necessitating surgical excision. This reinforces the need for heightened awareness and prompt surgical intervention when conservative measures fail, ensuring optimal patient outcomes and avoiding unnecessary discomfort or cosmetic issues. In conclusion, meticulous surgical technique and proper pre- and intraoperative disinfection are paramount in preventing postoperative complications such as conjunctival cysts. Early recognition and timely surgical intervention are essential for managing these cysts effectively. This case reinforces the importance for ophthalmic surgeons to remain vigilant in their surgical practices and to promptly address any postoperative complications, thereby improving surgical outcomes and enhancing patient care in strabismus surgery., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Takahashi et al.)

Background: Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic malignant tumor. The standard treatment for CCOC is surgical resection and adjuvant radiotherapy (RT). Radiotherapy is generally considered in inoperable cases. However, there are no reports on definitive RT for CCOC, and the role of RT in patients with inoperable CCOC remains unknown. Therefore, in this report, we present two cases of carbon-ion (C-ion) RT for CCOC., Case Presentation: In case 1, a 73-year-old man with mandibular CCOC presented with recurrence in the inferior temporal fossa after two tumor resections. The tumor was considered inoperable, and C-ion RT (57.6 Gy in 16 fractions) was administered. The tumor remained controlled even after 20 months of C-ion RT; however, the patient died of other causes. In case 2, a 34-year-old man with maxillary CCOC presented with recurrence in the left sinonasal region after two tumor resections. The tumor was considered inoperable, and C-ion RT (64 Gy in 16 fractions) was administered. However, recurrence was observed in the irradiated field 19 months after the treatment. Subsequently, C-ion RT (64 Gy in 16 fractions) was repeated for the recurrent tumors. Seven years and 6 months after the initial irradiation, the tumor remains controlled, and the patient is alive without any unexpected serious adverse events., Conclusion: C-ion RT may be an effective treatment option for patients with inoperable CCOC., (© 2024. The Author(s).)

Acinetobacter baumannii is a common pathogen associated with hospital-acquired pneumonia showing increased resistance to carbapenem and colistin antibiotics nowadays. Infections with A. baumannii cause high patient fatalities due to their capability to evade current antimicrobial therapies, emphasizing the urgency of developing viable therapeutics to treat A. baumannii -associated pneumonia. In this review, we explore current and novel therapeutic options for overcoming therapeutic failure when dealing with A. baumannii -associated pneumonia. Among them, antibiotic combination therapy administering several drugs simultaneously or alternately, is one promising approach for optimizing therapeutic success. However, it has been associated with inconsistent and inconclusive therapeutic outcomes across different studies. Therefore, it is critical to undertake additional clinical trials to ascertain the clinical effectiveness of different antibiotic combinations. We also discuss the prospective roles of novel antimicrobial therapies including antimicrobial peptides, bacteriophage-based therapy, repurposed drugs, naturally-occurring compounds, nanoparticle-based therapy, anti-virulence strategies, immunotherapy, photodynamic and sonodynamic therapy, for utilizing them as additional alternative therapy while tackling A. baumannii -associated pneumonia. Importantly, these innovative therapies further require pharmacokinetic and pharmacodynamic evaluation for safety, stability, immunogenicity, toxicity, and tolerability before they can be clinically approved as an alternative rescue therapy for A. baumannii -associated pulmonary infections.

Background/aim: There are two main subtypes of mucinous carcinoma (MC) based on the quantification of the mucinous component: the pure variant (pMC) and the mixed variant (mMC). pMC has been subdivided into pure A with a hypocellular variant, and pure B with a hypercellular variant., Patients and Methods: We retrospectively analyzed the clinicopathological features of 99 patients with MC who were treated at our institution from January 2002 to December 2014. We evaluated the expression profiles of markers, including mucin (MUC) family members, in the patients groups representing different MC subtypes by performing immunohistochemistry to identify factors involved in the differentiation and progression of MCs., Results: Among the 99 patients, 76 (76.8%) had pure mucinous carcinomas (pMC) and the other 23 (23.2%) had mixed mucinous carcinomas (mMC). Of the pMCs, 54 were pure A and 22 were pure B. The prognosis was worse for pure B than pure A and worse for mMC than pMC. Although there was no significant difference in clinicopathological factors between the pure A and pure B groups, immunohistochemical staining revealed differences in the localization of mucin MUC1 and β-catenin. A comparison of the pMC and mMC cases revealed more lymphovascular invasion in mMC and differences in the localization of β-catenin between the two groups., Conclusion: The patients' prognoses were significantly poorer depending on the histologic subtype (in the order pure A, pure B, and mixed). MUC1 localization and β-catenin were revealed as independent predictors contributing to the poorer prognosis., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A few reports have discussed the influence of inter-fractional position error and intra-fractional motion on dose distribution, particularly regarding a spread-out Bragg peak. We investigated inter-fractional and intra-fractional prostate position error by monitoring fiducial marker positions. In 2020, data from 15 patients with prostate cancer who received carbon-ion beam radiotherapy (CIRT) with gold markers were investigated. We checked marker positions before and during irradiation to calculate the inter-fractional positioning and intra-fractional movement and evaluated the CIRT dose distribution by adjusting the planning beam isocenter and clinical target volume (CTV) position. We compared the CTV dose coverages (CTV receiving 95% [V95%] or 98% [V98%] of the prescribed dose) between skeletal and fiducial matching irradiation on the treatment planning system. For inter-fractional error, the mean distance between the marker position in the planning images and that in a patient starting irradiation with skeletal matching was 1.49 ± 1.11 mm (95th percentile = 1.85 mm). The 95th percentile (maximum) values of the intra-fractional movement were 0.79 mm (2.31 mm), 1.17 mm (2.48 mm), 1.88 mm (4.01 mm), 1.23 mm (3.00 mm), and 2.09 mm (8.46 mm) along the lateral, inferior, superior, dorsal, and ventral axes, respectively. The mean V95% and V98% were 98.2% and 96.2% for the skeletal matching plan and 99.5% and 96.8% for the fiducial matching plan, respectively. Fiducial matching irradiation improved the CTV dose coverage compared with skeletal matching irradiation for CIRT for prostate cancer., (© 2024. The Author(s), under exclusive licence to Japanese Society of Radiological Technology and Japan Society of Medical Physics.)

Leber's hereditary optic atrophy (LHON) is a genetic optic neuropathy that is more prevalent in young males but can occur from childhood to old age. The primary cause is mitochondrial genetic mutations, which are associated with dysfunction of mitochondrial electron transport chain complex I. It manifests as acute to subacute visual impairment, often starting unilaterally but progressing to involve both eyes within weeks to months. Visual loss is severe, with many patients having corrected visual acuity below 0.1. The differential diagnosis of optic neuritis is essential, and assessments such as pupillary light reflex, fluorescein fundus angiography, and magnetic resonance imaging can be useful for differentiation. LHON should be considered as one of the differential diagnoses for optic neuritis, and collaboration between neurologists and ophthalmologists is crucial for accurate diagnosis and appropriate treatment.

The usefulness of moderately hypofractionated radiotherapy for localized prostate cancer has been extensively reported, but there are limited studies on proton beam therapy (PBT) using similar hypofractionation schedules. The aim of this prospective phase II study is to confirm the safety of a shortened PBT course using 70 Gy relative biological effectiveness (RBE) in 28 fractions. From May 2013 to June 2015, 102 men with localized prostate cancer were enrolled. Androgen deprivation therapy was administered according to risk classification. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.0. Of the 100 patients ultimately evaluated, 15 were classified as low risk, 43 as intermediate risk, and 42 as high risk. The median follow-up time of the surviving patients was 96 months (range: 60-119 months). The 5-year cumulative incidences of grade 2 gastrointestinal/genitourinary adverse events were 1% (95% CI: 0.1-6.9) and 4% (95% CI: 1.5-10.3), respectively; no grade ≥ 3 gastrointestinal/genitourinary adverse events were observed. The current study revealed a low incidence of late adverse events in prostate cancer patients treated with moderately hypofractionated PBT of 70 Gy (RBE) in 28 fractions, indicating the safety of this schedule., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective. To improve respiratory gating accuracy and radiation treatment throughput, we developed a generalized model based on a deep neural network (DNN) for predicting any given patient's respiratory motion. Approach. Our model uses long short-term memory (LSTM) based on a recurrent neural network (RNN), and improves upon common techniques. The first improvement is that the data input is not a one-dimensional sequence, but two-dimensional block data. This shortens the input sequence length, reducing computation time. Second, the output is not a scalar, but a sequence prediction. This increases the amount of available data, allowing improved prediction accuracy. For training and evaluation of our model, 434 sets of real-time position management data were retrospectively collected from clinical studies. The data were separated in a ratio of 4:1, with the larger set used for training models and the remaining set used for testing. We measured the accuracy of respiratory signal prediction and amplitude-based gating with prediction windows equaling 133, 333, and 533 ms. This new model was compared with the original LSTM and a non-recurrent DNN model. Main results. The mean absolute errors with the prediction window at 133, 333 and 533 ms were 0.036, 0.084, 0.119 with our model; 0.049, 0.14, 0.246 with the original LSTM-based model; and 0.041, 0.119, 0.16 with the non-recurrent DNN model, respectively. The computation time were 0.66 ms with our model; 0.63 ms the original LSTM-based model; 1.60 ms the non-recurrent DNN model, respectively. The accuracies of amplitude-based gating with the same prediction window settings and a duty cycle of approximately 50% were 98.3%, 95.8% and 92.7% with our model, 97.6%, 93.9% and 87.2% with the original LSTM-based model; and 97.9%, 94.3% and 89.5% with the non-recurrent DNN model, respectively. Significance. Our RNN algorithm for respiratory signal prediction successfully estimated tumor positions. We believe it will be useful in respiratory signal prediction technology., (© 2024 Institute of Physics and Engineering in Medicine.)

Background: Repurposed drugs with host-directed antiviral and immunomodulatory properties have shown promise in the treatment of COVID-19, but few trials have studied combinations of these agents. The aim of this trial was to assess the effectiveness of affordable, widely available, repurposed drugs used in combination for treatment of COVID-19, which may be particularly relevant to low-resource countries., Methods: We conducted an open-label, randomized, outpatient, controlled trial in Thailand from October 1, 2021, to June 21, 2022, to assess whether early treatment within 48-h of symptoms onset with combinations of fluvoxamine, bromhexine, cyproheptadine, and niclosamide, given to adults with confirmed mild SARS-CoV-2 infection, can prevent 28-day clinical deterioration compared to standard care. Participants were randomly assigned to receive treatment with fluvoxamine alone, fluvoxamine + bromhexine, fluvoxamine + cyproheptadine, niclosamide + bromhexine, or standard care. The primary outcome measured was clinical deterioration within 9, 14, or 28 days using a 6-point ordinal scale. This trial is registered with ClinicalTrials.gov (NCT05087381)., Findings: Among 1900 recruited, a total of 995 participants completed the trial. No participants had clinical deterioration by day 9, 14, or 28 days among those treated with fluvoxamine plus bromhexine (0%), fluvoxamine plus cyproheptadine (0%), or niclosamide plus bromhexine (0%). Nine participants (5.6%) in the fluvoxamine arm had clinical deterioration by day 28, requiring low-flow oxygen. In contrast, most standard care arm participants had clinical deterioration by 9, 14, and 28 days. By day 9, 32.7% (110) of patients in the standard care arm had been hospitalized without requiring supplemental oxygen but needing ongoing medical care. By day 28, this percentage increased to 37.5% (21). Additionally, 20.8% (70) of patients in the standard care arm required low-flow oxygen by day 9, and 12.5% (16) needed non-invasive or mechanical ventilation by day 28. All treated groups significantly differed from the standard care group by days 9, 14, and 28 (p < 0.0001). Also, by day 28, the three 2-drug treatments were significantly better than the fluvoxamine arm (p < 0.0001). No deaths occurred in any study group. Compared to standard care, participants treated with the combination agents had significantly decreased viral loads as early as day 3 of treatment (p < 0.0001), decreased levels of serum cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) as early as day 5 of treatment, and interleukin-8 (IL-8) by day 7 of treatment (p < 0.0001) and lower incidence of post-acute sequelae of COVID-19 (PASC) symptoms (p < 0.0001). 23 serious adverse events occurred in the standard care arm, while only 1 serious adverse event was reported in the fluvoxamine arm, and zero serious adverse events occurred in the other arms., Interpretation: Early treatment with these combinations among outpatients diagnosed with COVID-19 was associated with lower likelihood of clinical deterioration, and with significant and rapid reduction in the viral load and serum cytokines, and with lower burden of PASC symptoms. When started very soon after symptom onset, these repurposed drugs have high potential to prevent clinical deterioration and death in vaccinated and unvaccinated COVID-19 patients., Funding: Ped Thai Su Phai (Thai Ducks Fighting Danger) social giver group., Competing Interests: Dr. Reiersen is listed as an inventor on a patent application related to methods of treating COVID-19 (including Sigma1 agonists and specifically fluvoxamine), which was filed by Washington University in St. Louis. No other author declares any potential conflict of interest or competing financial or non-financial interest in relation to the manuscript., (© 2024 The Author(s).)

Introduction: The standard therapy for stage I NSCLC is surgery, but some operable patients refuse this option and instead undergo radiotherapy. Carbon-ion radiotherapy (CIRT) is a type of radiotherapy. The Japanese prospective nationwide registry study on CIRT began in 2016. Here, we analyzed real-world clinical outcomes of CIRT for operable patients with stage I NSCLC., Methods: All patients with operable stage I NSCLC treated with CIRT in Japan between 2016 and 2018 were enrolled. The dose fractionations for CIRT were selected from several options approved by the Japanese Society for Radiation Oncology. CIRT was delivered to the primary tumor, not to lymph nodes., Results: The median follow-up period was 56 months. Among 136 patients, 117 (86%) had clinical stage IA NSCLC and 19 (14%) had clinical stage IB NSCLC. There were 50 patients (37%) diagnosed clinically without having been diagnosed histologically. Most tumors (97%) were located in the periphery. The 5-year overall survival, cause-specific survival, progression-free survival, and local control rate were 81.8% (95% confidence interval [CI]: 75.1-89.2), 91.2% (95% CI: 86.0-96.8), 65.9% (95% CI: 58.2-74.6), and 95.8% (95% CI: 92.3-99.5), respectively. Multivariate analysis identified age as a significant factor for overall survival (p = 0.018), whereas age and consolidation/tumor ratio (p = 0.010 and p = 0.004) were significant factors for progression-free survival. There was no grade 4 or higher toxicity. Grade 3 radiation pneumonitis occurred in one patient., Conclusions: This study reports the long-term outcomes of CIRT for operable NSCLC in the real world. CIRT for operable patients has been found to have favorable outcomes, with tolerable toxicity., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

The aim of this study is to assess the efficacy and safety of ablative carbon ion radiotherapy (CIRT) for early stage central non-small cell lung cancer (NSCLC). We retrospectively reviewed 30 patients who had received CIRT at 68.4 Gy in 12 fractions for central NSCLC in 2006-2019. The median age was 75 years, and the median Karnofsky Performance Scale score was 90%. All patients had concomitant chronic obstructive pulmonary disease, and 20 patients (67%) were considered inoperable. In DVH analysis, the median lung V5 and V20 were 15.5% and 10.4%, and the median Dmax, D0.5cc, D2cc of proximal bronchial tree was 65.6 Gy, 52.8 Gy, and 10.0 Gy, respectively. At a median follow-up of 43 months, the 3-year overall survival, disease-specific survival, and local control rates were 72.4, 75.8, and 88.7%, respectively. Two patients experienced grade 3 pneumonitis, but no grade ≥3 adverse events involving the mediastinal organs occurred. Ablative CIRT is feasible and effective for central NSCLC and could be considered as a treatment option, especially for patients who are intolerant of other curative treatments.

Patients with lung cancer complicated by interstitial pneumonia (IP) often lose treatment options early owing to acute exacerbation of IP concerns. Carbon-ion radiotherapy (CIRT) can provide superior tumor control and low toxicity at high dose concentrations. We conducted a retrospective analysis of the efficacy and tolerability of a single-fraction CIRT using 50 Gy for IP-complicated lung cancer. The study included 50 consecutive patients treated between April 2013 and September 2022, whose clinical stage of lung cancer (UICC 7th edition) was 1A:1B:2A:2B = 32:13:4:1. Of these, 32 (64%) showed usual interstitial pneumonia patterns. With a median follow-up of 23.5 months, the 3-year overall survival (OS), cause-specific survival, and local control rates were 45.0, 75.4, and 77.8%, respectively. The median lung V5 and V20 were 10.0 and 5.2%, respectively (mean lung dose, 2.6 Gy). The lung dose, especially lung V20, showed a strong association with OS ( p = 0.0012). Grade ≥ 2 pneumonia was present in six patients (13%), including two (4%) with suspected grade 5. CIRT can provide a relatively safe and curative treatment for patients with IP-complicated lung cancer. However, IP increases the risk of severe radiation pneumonitis, and further studies are required to assess the appropriate indications.

This study investigated the potential of using SARS-CoV-2 viral concentrations in dust as an additional surveillance tool for early detection and monitoring of COVID-19 transmission. Dust samples were collected from 8 public locations in 16 districts of Bangkok, Thailand, from June to August 2021. SARS-CoV-2 RNA concentrations in dust were quantified, and their correlation with community case incidence was assessed. Our findings revealed a positive correlation between viral concentrations detected in dust and the relative risk of COVID-19. The highest risk was observed with no delay (0-day lag), and this risk gradually decreased as the lag time increased. We observed an overall decline in viral concentrations in public places during lockdown, closely associated with reduced human mobility. The effective reproduction number for COVID-19 transmission remained above one throughout the study period, suggesting that transmission may persist in locations beyond public areas even after the lockdown measures were in place., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Objective. The prostate moves in accordance with the movement of surrounding organs. Tumor position can change by ≥3 mm during radiotherapy. Given the difficulties of visualizing the prostate fluoroscopically, fiducial markers are generally implanted into the prostate to monitor its motion during treatment. Recently, internally motion guidance methods of the prostate using a 99.5% gold/0.5% iron flexible notched wire fiducial marker (Gold Anchor® , Naslund Medical AB, Huddinge, Sweden), which requires a 22 gauge needle, has been used. However, because the notched wire can retain its linear shape, acquire a spiral shape, or roll into an irregular ball, detecting it on fluoroscopic images in real-time incurs higher computation costs. Approach. We developed a fiducial tracking algorithm to achieve real-time computation. The marker is detected on the first image frame using a shape filter that employs inter-class variance for the marker likelihood calculated by the filter, focusing on the large difference in densities between the marker and its surroundings. After the second frame, the marker is tracked by adding to the shape filter the similarity to the template cropped from the area around the marker position detected in the first frame. We retrospectively evaluated the algorithm's marker tracking accuracy for ten prostate cases, analyzing two fractions in each case. Main results. Tracking positional accuracy averaged over all patients was 0.13 ± 0.04 mm (mean ± standard deviation, Euclidean distance) and 0.25 ± 0.09 mm (95th percentile). Computation time was 2.82 ± 0.20 ms/frame averaged over all frames. Significance. Our algorithm successfully and stably tracked irregularly-shaped markers in real time., (© 2024 Institute of Physics and Engineering in Medicine.)

Purpose: In this study, we aimed to compare blood flow changes in the optic nerve head (ONH) during horizontal ocular duction among normal, primary open-angle glaucoma (POAG), and normal-tension glaucoma (NTG) eyes., Methods: In this cross-sectional study, we included 90 eyes from 90 participants (30 control eyes, 30 POAG eyes, and 30 NTG eyes). ONH blood flow was measured with laser speckle flowgraphy using an external fixation light to induce central gaze, abduction, and adduction at 30 degrees for each eye. The mean blur rate (MBR) of the entire ONH area (MA), vascular region (MV), and tissue region (MT), and the change ratio were analyzed. The change ratio was defined as abduction or adduction value/central gaze value., Results: In the control group, MA significantly decreased during adduction (22.9 ± 3.7) compared with that during central gaze (23.6 ± 3.9, P < 0.05). In the POAG group, MA (adduction = 17.4 ± 3.8 and abduction = 17.3 ± 3.6) and MV (adduction = 37.9 ± 5.6 and abduction = 38.0 ± 5.6) significantly decreased during adduction and abduction compared with those during central gaze (18.0 ± 4.1 and 39.5 ± 6.3, respectively, P < 0.05). In the NTG group, MA significantly decreased during adduction (17.4 ± 4.2) compared with that during central gaze (18.1 ± 4.6) and abduction (18.1 ± 4.8, P < 0.05). The change ratio did not differ between the glaucoma and control groups., Conclusions: ONH blood flow decreased during horizontal ocular duction regardless of normal or glaucoma states; however, the change ratio was comparable between the normal and glaucoma groups.

Purpose: Treatment outcomes of definitive photon radiation therapy for nonmetastatic castration-resistant prostate cancer (nmCRPC) are reportedly unsatisfactory. Carbon ion radiation therapy (CIRT) has shown favorable tumor control in various malignancies, including radioresistant tumors. Therefore, we retrospectively evaluated the clinical outcomes of CIRT for nmCRPC., Methods and Materials: Patients with nmCRPC (N0M0) treated with CIRT at a total dose of 57.6 Gy (relative biologic effectiveness) in 16 fractions or 51.6 Gy (relative biologic effectiveness) in 12 fractions were included. The castration-resistant status received a diagnosis based on prostate-specific antigen kinetics showing a monotonic increase during primary androgen deprivation therapy or the need to change androgen deprivation therapy. Clinical factors associated with patient prognosis were explored. Twenty-three consecutive patients were identified from our database. The median follow-up period was 63.6 months (range, 14.1-120)., Results: Seven patients developed biochemical relapse, 6 had clinical relapse, and 4 died of the disease. The 5-year overall survival, local control rate, biochemical relapse-free survival, and clinical relapse-free survival were 87.5%, 95.7%, 70.3%, and 75.7%, respectively. One patient with diabetes mellitus requiring insulin injections and taking antiplatelet and anticoagulant drugs developed grade 3 hematuria and bladder tamponade after CIRT. None of the patients developed grade 4 or worse toxicity., Conclusions: The present findings indicate the acceptable safety and favorable efficacy of CIRT, encouraging further research on CIRT for nmCRPC., Competing Interests: Kazuhiro Suzuki has potential financial conflicts of interest due to consultancies in Takeda Pharmaceutical, Astellas Pharma, Daiichi-Sankyo, AstraZeneca, Sanofi, Janssen, and Bayer and grants received from Takeda Pharmaceutical, Astellas Pharma, and Daiichi-Sankyo. Tatsuya Ohno has potential financial conflicts of interest due to research funding from Hitachi Ltd Hiroyuki Katoh has potential financial conflicts of interest due to research funding from Toshiba Energy Systems & Solutions Corporation., (© 2023 The Authors.)

[Purpose] This study aimed to investigate the usefulness of a quality index in gait for proximal femur fractures. [Participants and Methods] In this study, 20 females with postoperative proximal femur fracture in the preparation phase for discharge (femur fracture group) aged ≥60 years (63.0 ± 3.0 years) and 20 healthy older females (healthy group) participated (75.7 ± 7.7 years) (n=40). Measurements were conducted at comfortable and maximal gait speeds. Power spectrum entropy (PSE), harmonic ratio (HR), and modified HR (mHR), which are smoothness indices, were calculated from the measured data in each of the three axial directions and compared. [Results] The healthy and femur fracture groups showed significant differences in the PSE, HR, and mHR for comfortable and maximal gait speed in the lateral and vertical directions. Furthermore, all directions between the HR and mHR in the femur fracture group had significant differences. [Conclusion] The usefulness of the PSE, HR, and mHR as quality evaluation indices of gait was demonstrated in patients with postoperative femur fractures after unilateral disability., Competing Interests: None., (2023©by the Society of Physical Therapy Science. Published by IPEC Inc.)

We sought to accelerate 2D/3D image registration computation time using image synthesis with a deep neural network (DNN) to generate digitally reconstructed radiographic (DRR) images from X-ray flat panel detector (FPD) images. And we explored the feasibility of using our DNN in the patient setup verification application. Images of the prostate and of the head and neck (H&N) regions were acquired by two oblique X-ray fluoroscopic units and the treatment planning CT. DNN was designed to generate DRR images from the FPD image data. We evaluated the quality of the synthesized DRR images to compare the ground-truth DRR images using the peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM). Image registration accuracy and computation time were evaluated by comparing the 2D-3D image registration algorithm using DRR and FPD image data with DRR and synthesized DRR images. Mean PSNR values were 23.4 ± 3.7 dB and 24.1 ± 3.9 dB for the pelvic and H&N regions, respectively. Mean SSIM values for both cases were also similar (= 0.90). Image registration accuracy was degraded by a mean of 0.43 mm and 0.30°, it was clinically acceptable. Computation time was accelerated by a factor of 0.69. Our DNN successfully generated DRR images from FPD image data, and improved 2D-3D image registration computation time up to 37% in average., (© 2023. Australasian College of Physical Scientists and Engineers in Medicine.)

Significance: This study highlights the importance of twilight adaptation for reliable assessment of low-luminance visual acuity and understanding the relationship between low-luminance visual acuity and ocular aberrations., Purpose: The human eye experiences reduced visual acuity as luminance decreases owing to reduced retinal and optical resolutions; however, the details are unclear. This study aimed to quantify the effects of refraction, pupil diameter, and ocular aberrations on visual acuity during the transition from high- to low-light environments, thereby contributing to the standardization of low-luminance visual acuity measurements., Methods: In total, 27 older participants with a mean age of 70.0 ± 4.1 years were included in this study. Visual acuity was measured according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol with three luminance conditions: high luminance (300 cd/m 2 ), low luminance (10 cd/m 2 ), and low luminance with short-term (15-minute) twilight adaptation (10 cd/m 2 )., Results: The mean logarithm of minimum angle of resolution values of visual acuity were -0.09 ± 0.09, 0.10 ± 0.13, and 0.03 ± 0.09 at 300, 10, and 10 cd/m 2 with twilight adaptation, respectively. Multiple regression analysis determined that spherical aberration ( P < .005) and tetrafoil ( P < .005) were significant factors associated with low-luminance visual acuity after twilight adaptation, with an adjusted R2 value of 0.35 for this model ( P < .005)., Conclusions: Although the influence of ocular aberrations on low-luminance visual acuity may be relatively modest compared with neural effects, it remains a crucial factor that should not be overlooked. The absence of twilight (or dark) adaptation can cause ocular aberrations and neural effects, potentially leading to inaccuracies in the measurement of low-luminance visual acuity., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2023 American Academy of Optometry.)

Purpose: To evaluate the safety and pathologic complete response (pCR) rate of radiation therapy with atezolizumab as bladder-preserving therapy for invasive bladder cancer., Methods and Materials: A multicenter, phase 2 study was conducted with patients with clinically T2-3 or very-high-risk T1 bladder cancer who were poor candidates for or refused radical cystectomy. The interim analysis of pCR is reported as a key secondary endpoint ahead of the progression-free survival rate primary endpoint. Radiation therapy (41.4 Gy to the small pelvic field and 16.2 Gy to the whole bladder) was given in addition to 1200 mg intravenous atezolizumab every 3 weeks. After 24 treatment weeks, response was assessed after transurethral resection, and tumor programmed cell death ligand-1 (PD-L1) expression was assessed using tumor-infiltrating immune cell scores., Results: Forty-five patients enrolled from January 2019 to May 2021 were analyzed. The most common clinical T stage was T2 (73.3%), followed by T1 (15.6%) and T3 (11.1%). Most tumors were solitary (77.8%), small (<3 cm) (57.8%), and without concurrent carcinoma in situ (88.9%). Thirty-eight patients (84.4%) achieved pCR. High pCR rates were achieved in older patients (90.9%) and in patients with high PD-L1-expressing tumors (95.8% vs 71.4%). Adverse events (AEs) occurred in 93.3% of patients, with diarrhea being the most common (55.6%), followed by frequent urination (42.2%) and dysuria (20.0%). The frequency of grade 3 AEs was 13.3%, whereas no grade 4 AEs were observed., Conclusions: Combination therapy with radiation therapy and atezolizumab provided high pCR rates and acceptable toxicity, indicating it could be a promising option for bladder preservation therapy., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Given the rise of multidrug-resistant (MDR) Pseudomonas aeruginosa infections, alternative treatments are needed. Anti-pseudomonal phage therapy shows promise, but its clinical application is limited due to the development of resistance and a lack of biofilm penetration. Recently, adjuvants like CaEDTA have shown the ability to enhance the effectiveness of combined antimicrobial agents. Here, we tested a phage-adjuvant combination and demonstrated the effectiveness of intranasally inhaled phage (KKP10) + CaEDTA in addition to ceftazidime/avibactam (CZA) for chronic P. aeruginosa lung infections. The results emphasize that intranasal inhalation of phage along with CaEDTA can successfully re-sensitize MDR P. aeruginosa to CZA in a triple combination treatment. This promising approach shows potential as a therapy for chronic respiratory tract infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Standardised measurement protocols for grip strength remained unclear due to variations in values depending on the device and measurement method. The load cell hand dynamometer has recently been developed. This study aims to investigate the reliability of the load cell dynamometer by comparing it to the Jamar dynamometer, which is considered the gold standard, and to identify a reliable and practical measurement method. Methods: This study included 80 healthy hospital workers (mean age of 40.1 years). All measurements were performed seated, with the elbow flexed 90° and the grip span at the second handle (approximately 50 mm) for the Jamar dynamometer, and with the elbow extended and the grip span fixed at 55 mm for the load cell dynamometer. Grip strength was measured three times on each hand using two dynamometers, and the same tests were repeated on different days. Test-retest reliability, the association between the two devices and the agreement between the two measurement methods were assessed using the intraclass correlation coefficient (ICC), Pearson correlation and the Bland-Altman analysis. Results: The ICC of the one measurement was lower than that of three measurements for both dynamometers, but was above 0.858 in all groups, indicating sufficient reliability with one-time measurement. Additionally, the ICC for different days revealed good reliability (Jamar: >0.830, load cell: >0.772). The load cell dynamometer showed significantly lower values in all measurements despite the excellent correlation ( r > 0.70) and the agreement between the two dynamometers. Conclusions: This study revealed sufficient reliability of the load cell dynamometer with the standardised measurement method, but it should be noted the lower values compared to the Jamar dynamometer. Additionally, one-time measurement reliability is adequate for practical use by standardising the measurement methods for both dynamometers. Level of Evidence: Level III (Diagnostic).

This systematic review was performed to investigate the superiority of proton beam therapy (PBT) to photon-based radiotherapy (RT) in treating esophageal cancer patients, especially those with poor cardiopulmonary function. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 2000 to August 2020 for studies evaluating one end point at least as follows; overall survival, progression-free survival, grade ≥ 3 cardiopulmonary toxicities, dose-volume histograms, or lymphopenia or absolute lymphocyte counts (ALCs) in esophageal cancer patients treated with PBT or photon-based RT. Of 286 selected studies, 23 including 1 randomized control study, 2 propensity matched analyses, and 20 cohort studies were eligible for qualitative review. Overall survival and progression-free survival were better after PBT than after photon-based RT, but the difference was significant in only one of seven studies. The rate of grade 3 cardiopulmonary toxicities was lower after PBT (0-13%) than after photon-based RT (7.1-30.3%). Dose-volume histograms revealed better results for PBT than photon-based RT. Three of four reports evaluating the ALC demonstrated a significantly higher ALC after PBT than after photon-based RT. Our review found that PBT resulted in a favorable trend in the survival rate and had an excellent dose distribution, contributing to reduced cardiopulmonary toxicities and a maintained number of lymphocytes. These results warrant novel prospective trials to validate the clinical evidence., (© 2023. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: Studies that quantify the quality of sit-to-stand-to-sit (STS) motions, particularly in terms of smoothness, are limited. Thus, this study aimed to investigate the possibility and usefulness of quality evaluation during STS motions., Methods: This cross-sectional study enrolled 36 females aged >60 years, including 18 females each in the healthy and hip fracture groups. Measurements were performed at two different speeds: five STS as fast as possible (STSF) and two seconds for each motion (STS2s). Indices of smoothness, including harmonic ratio (HR) and power spectrum entropy (PSE), were calculated and compared from the measured data in each of the three axial directions., Results: HR in the vertical direction was significantly higher in the healthy group (STSF: 3.65 ± 1.74, STS2s: 3.42 ± 1.54) than in the hip fracture group (STSF: 2.67 ± 1.01, STS2s: 2.58 ± 0.83) for STSF and STS2s. Furthermore, PSE for all directions and triaxial composites were significantly lower for STS2s (the healthy group (mediolateral (ML): 7.63 ± 0.31, vertical (VT): 7.46 ± 0.22, anterior-posterior (AP): 7.47 ± 0.15, triaxial: 7.45 ± 0.25), the hip fracture group (ML: 7.82 ± 0.16, VT: 7.63 ± 0.16, AP: 7.61 ± 0.17, triaxial: 7.66 ± 0.17))., Conclusions: This study suggests the usefulness of HR and PSE as quality evaluations for STS motions.

The aim of this retrospective study was to identify clinical predictors of early biochemical recurrence (BCR) in patients with high-risk prostate cancer (PCa) treated with carbon-ion radiotherapy (CIRT) and androgen deprivation therapy (ADT). A total of 670 high-risk PCa patients treated with CIRT and ADT were included in the study. Early BCR was defined as recurrence occurring during adjuvant ADT after CIRT or within 2 years after completion of ADT. Univariate and multivariate analyses were performed to identify clinical predictors of early BCR. Patients were also classified according to the Systemic Therapy in Advancing or Metastatic Prostate cancer (STAMPEDE) PCa classification. Early BCR was observed in 5.4% of the patients. Multivariate analysis identified clinical T3b stage and ≥75% positive biopsy cores as clinical predictors of early BCR after CIRT and ADT. The STAMPEDE PCa classification was also significantly associated with early BCR based on univariate analysis. These predictors can help clinicians identify patients who are at risk of early BCR. In the future, combination therapy of ADT with abiraterone may be an option for high-risk PCa patients who are at risk of early BCR, based on the results of the STAMPEDE study.

High population density and tourism in Southeast Asia increase the risk of mpox due to frequent interpersonal contacts. Our wastewater surveillance in six Southeast Asian countries revealed positive signals for Monkeypox virus (MPXV) DNA, indicating local transmission. This alerts clinicians and helps allocate resources like testing, vaccines and therapeutics in resource-limited countries., (© International Society of Travel Medicine 2023. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

We developed a deep neural network (DNN) to generate X-ray flat panel detector (FPD) images from digitally reconstructed radiographic (DRR) images. FPD and treatment planning CT images were acquired from patients with prostate and head and neck (H&N) malignancies. The DNN parameters were optimized for FPD image synthesis. The synthetic FPD images' features were evaluated to compare to the corresponding ground-truth FPD images using mean absolute error (MAE), peak signal-to-noise ratio (PSNR), and structural similarity index measure (SSIM). The image quality of the synthetic FPD image was also compared with that of the DRR image to understand the performance of our DNN. For the prostate cases, the MAE of the synthetic FPD image was improved (= 0.12 ± 0.02) from that of the input DRR image (= 0.35 ± 0.08). The synthetic FPD image showed higher PSNRs (= 16.81 ± 1.54 dB) than those of the DRR image (= 8.74 ± 1.56 dB), while SSIMs for both images (= 0.69) were almost the same. All metrics for the synthetic FPD images of the H&N cases were improved (MAE 0.08 ± 0.03, PSNR 19.40 ± 2.83 dB, and SSIM 0.80 ± 0.04) compared to those for the DRR image (MAE 0.48 ± 0.11, PSNR 5.74 ± 1.63 dB, and SSIM 0.52 ± 0.09). Our DNN successfully generated FPD images from DRR images. This technique would be useful to increase throughput when images from two different modalities are compared by visual inspection., (© 2023. Australasian College of Physical Scientists and Engineers in Medicine.)

Purpose: To study the spatial association of magnetic resonance imaging (MRI) contrast enhancement (CE) areas with visual field defect (VFD) asymmetry in initial cases of optic neuritis (ON) with altitudinal hemianopsia (AH) with reference to nonarteritic anterior ischemic optic neuropathy (NAION) with AH., Study Design: Multicenter, cross-sectional study., Methods: The present study comprised 19 ON patients and 20 NAION patients with AH who underwent orbital contrast fat-suppressed MRI. The signal-to-intensity ratio (SIR) was calculated by dividing the maximum CE of the optic nerve by the mean CE of the cerebral white matter in 11 coronal sections at 3-mm intervals from immediately posterior to the eyeball to the optic chiasm. Sections in ON patients with an SIR exceeding the mean plus 2 standard deviations of the SIR at the corresponding section in the NAION group were considered abnormal. The correlation between upper-to-lower CE asymmetry in the maximum SIR section and VFD counterpart was determined., Results: The ON group had significantly higher maximum SIR than that of the NAION group (1.77 ± 0.88 vs. 1.25 ± 0.32; P < .01). Seven of the 19 patients had sections with abnormally high CE extending posteriorly beyond the orbital apex. Significant spatial correspondence was observed between CE and VFD asymmetry (r s = 0.563; P = .015) in the ON group but not in the NAION group (r s  = - 0. 048; P = .850)., Conclusions: ON patients with AH frequently show CE even in the intracerebral optic nerve, maintaining a moderate structure-function correspondence., (© 2023. Japanese Ophthalmological Society.)

Although there is a substantial amount of data on the clinical characteristics, diagnostic criteria, and pathogenesis of myelin oligodendrocyte glycoprotein (MOG) autoantibody-associated disease (MOGAD), there is still uncertainty regarding the MOG protein function and the pathogenicity of anti-MOG autoantibodies in this disease. It is important to note that the disease characteristics, immunopathology, and treatment response of MOGAD patients differ from those of anti-aquaporin 4 antibody-positive neuromyelitis optica spectrum disorders (NMOSDs) and multiple sclerosis (MS). The clinical phenotypes of MOGAD are varied and can include acute disseminated encephalomyelitis, transverse myelitis, cerebral cortical encephalitis, brainstem or cerebellar symptoms, and optic neuritis. The frequency of optic neuritis suggests that the optic nerve is the most vulnerable lesion in MOGAD. During the acute stage, the optic nerve shows significant swelling with severe visual symptoms, and an MRI of the optic nerve and brain lesion tends to show an edematous appearance. These features can be alleviated with early extensive immune therapy, which may suggest that the initial attack of anti-MOG autoantibodies could target the structures on the blood-brain barrier or vessel membrane before reaching MOG protein on myelin or oligodendrocytes. To understand the pathogenesis of MOGAD, proper animal models are crucial. However, anti-MOG autoantibodies isolated from patients with MOGAD do not recognize mouse MOG efficiently. Several studies have identified two MOG epitopes that exhibit strong affinity with human anti-MOG autoantibodies, particularly those isolated from patients with the optic neuritis phenotype. Nonetheless, the relations between epitopes on MOG protein remain unclear and need to be identified in the future.

Equitable SARS-CoV-2 surveillance in low-resource communities lacking centralized sewers is critical as wastewater-based epidemiology (WBE) progresses. However, large-scale studies on SARS-CoV-2 detection in wastewater from low-and middle-income countries is limited because of economic and technical reasons. In this study, wastewater samples were collected twice a month from 186 urban and rural subdistricts in nine provinces of Thailand mostly having decentralized and non-sewered sanitation infrastructure and analyzed for SARS-CoV-2 RNA variants using allele-specific RT-qPCR. Wastewater SARS-CoV-2 RNA concentration was used to estimate the real-time incidence and time-varying effective reproduction number (R e ). Results showed an increase in SARS-CoV-2 RNA concentrations in wastewater from urban and rural areas 14-20 days earlier than infected individuals were officially reported. It also showed that community/food markets were "hot spots" for infected people. This approach offers an opportunity for early detection of transmission surges, allowing preparedness and potentially mitigating significant outbreaks at both spatial and temporal scales., Competing Interests: No author declares any potential conflict of interest or competing financial or non-financial interest in relation to the manuscript., (© 2023 The Author(s).)

The emergence of an aging society and technological advances have made radiotherapy, especially stereotactic body radiotherapy (SBRT), a common alternative to surgery for elderly patients with early stage non-small-cell lung cancer (NSCLC). Carbon-ion radiotherapy (CIRT) is also an attractive treatment option with potentially lower toxicity for elderly patients with comorbidities. We compared the clinical outcomes of the two modalities using Japanese multicenter data. SBRT (n = 420) and single-fraction CIRT (n = 70) data for patients with stage I NSCLC from 20 centers were retrospectively analyzed. Contiguous patients ≥ 80 years of age were enrolled, and overall survival (OS), disease-specific survival (DSS), local control (LC), and adverse event rates were compared. The median age was 83 years in both groups and the median follow-up periods were 28.5 and 42.7 months for SBRT and CIRT, respectively. The 3-year OS, DSS, and LC rates were 76.0% vs. 72.3% ( p = 0.21), 87.5% vs. 81.6% ( p = 0.46), and 79.2% vs. 78.2% ( p = 0.87), respectively, for the SBRT vs. CIRT groups. Regarding toxicity, 2.9% of the SBRT group developed grade ≥ 3 radiation pneumonitis, whereas none of the CIRT group developed grade ≥ 2 radiation pneumonitis. SBRT and CIRT in elderly patients showed similar survival and LC rates, although CIRT was associated with less severe radiation pneumonitis.