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Background: Carotid webs are a potential cause of occult cerebral infarction. Although they occur frequently, proper diagnosis and treatment are crucial; surgery has been shown to provide a good outcome. Although thrombus on the carotid web have been reported, digital subtraction angiography (DSA)-confirmed cases of pre-dispersed thrombus are rare. In this study, we report a case in which a thrombus on the carotid web concealed a shelf-like defect, complicating its diagnosis., Case Description: A 47-year-old woman without stroke risk factors presented to our hospital with aphasia and right hemiplegia. On arrival, the symptoms had improved. Magnetic resonance (MR) imaging showed left middle cerebral artery stenosis; however, there was no cerebral infarction. DSA was performed post-admission to examine middle cerebral artery stenosis, which showed no middle cerebral artery stenosis but left internal carotid artery (ICA) origin stenosis and contrast pooling. We diagnosed a transient ischemic attack due to artery-to-artery embolism caused by left ICA stenosis and accompanied by a contralateral carotid web. The same symptoms appeared 6 days later. MR imaging showed a new cerebral infarction and the left middle cerebral artery occlusion. A mechanical thrombectomy procedure revealed a change in ICA origin shape compared to the 1 st time, with a shelf-like defect within the carotid web. She subsequently underwent carotid artery stenting and was discharged with mild dysesthesia in her right fingers (modified Rankin Scale of 1)., Conclusion: Thrombus on the carotid web conceals characteristic shelf-like defects and may cause misdiagnosis. However, contrast pooling and contralateral carotid web are important findings for early treatment., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Objectives: The linear no-threshold (LNT) model, which has been used for radiation protection purposes, was developed based on the assumption that exposure to even a small amount of radiation may cause cancer. However, although it is known in carcinogenesis that there is variation in radiation sensitivity among individuals, the LNT model does not adequately consider radiosensitive subgroups. In this paper, we represent susceptibility to contract cancer by radiation exposure by means of the threshold of a dose-response function, introduce an assumption that the thresholds are random to represent the variation of the radiosensitivity among individuals in a susceptible subgroup. We propose a novel method, the random threshold (RT) model, for determining the safe dose limit for the subgroup to protect cancer-susceptible individuals from radiation exposure. Conclusion: The proposed method is illustrated by targeting ATM gene (a cancer-susceptible gene) mutation carriers as a radiosensitive subgroup. For cancer risk associated with low-dose radiation exposure, the contribution of radiosensitivity cannot be ignored, thus the RT model would be more suitable for risk protection for radiosensitive subgroups instead of the LNT model. We also notice that it could be widely applicable for risk protection of not only low-dose radiation but also environmental pollutants., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: There is a dearth of studies on the efficacy and safety of the tyrosine kinase inhibitors osimertinib (OSI) and gefitinib (GEF) in treating epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC), even in patients with poor performance status (PS)., Methods: We retrospectively reviewed and compared data of 113 patients with EGFR mutation-positive NSCLC with Eastern Cooperative Oncology Group PS 2-4 who were administered OSI 80 mg/day or GEF 250 mg/day from May 2016 to March 2022., Results: The GEF group (39 patients; median age: 74 years) included 20 patients with a PS of 2, 17 with a PS of 3, and 2 with a PS of 4. The OSI group (74 patients; median age: 76 years) included 48 patients with a PS of 2, 24 with a PS of 3, and 2 with a PS of 4. The overall response rates were 69% and 66% in the GEF and OSI groups, respectively. The disease control and PS improvement rates were 89% and 51% in both groups, respectively. The median progression-free survival in the GEF and OSI groups was 6.9 and 9.2 months, respectively (p = 0.15). The OSI group experienced better overall survival than the GEF group (median: 20.9 vs. 13.0 months, p = 0.0031). The incidence of pneumonitis was 10% and 11% in the GEF and OSI groups, respectively. One treatment-related death owing to pneumonitis occurred in the GEF group., Conclusions: OSI may be a useful treatment for untreated EGFR mutation-positive NSCLC with poor PS., Competing Interests: Declaration of competing interest Kazuhisa Nakashima has received personal fees from Taiho Pharmaceutical, Chugai Pharma, AstraZeneca, Eli Lilly Japan, Nippon Kayaku, and Bristol-Myers Squibb. Hiroaki Kodama has received personal fees from Chugai Pharma and Novartis Pharma. Haruyasu Murakami has received personal fees from Chugai Pharma, Daiichi Sankyo, AstraZeneca, Takeda, Amgen, Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Pfizer, Novartis, Eli Lilly Japan, Taiho Pharmaceutical, Eisai, and Nippon Kayaku, grants from Chugai Pharma, AstraZeneca, Abbvie, Daiichi Sankyo, IQvia, Taiho Pharmaceutical and Bayer. Toshiaki Takahashi has received personal fees from AstraZeneca and MSD, and grants from Chugai Pharma, MSD, Eli Lilly Japan, Merck Biopharma Japan, AnHeart Therapeutics Inc., and Amgen. Kosuke Hamai has received personal fees from Boehringer Ingelheim, Eli Lilly Japan, AstraZeneca, Ono Pharmaceutical, Chugai Pharma, Merck & Co., and Taiho Pharmaceutical. Nobuhisa Ishikawa has received personal fees from AstraZeneca, Boehringer Ingelheim, Novartis, Ono Pharmaceutical, Eli Lilly Japan, Chugai Pharma, Taiho Pharmaceutical, MSD, Takeda, and Pfizer. Shoichi Kuyama has received personal fees from Chugai Pharma, Boehringer Ingelheim, Pfizer, MSD, Kyowa Kirin, Daiichi Sankyo, Novartis, Bristol-Myers Squibb, Eli Lilly Japan, AstraZeneca, Taiho Pharmaceutical, Hisamitsu Pharmaceutical, and Nippon Kayaku. Takeshi Isobe has received personal fees from MSD, AstraZeneca, Ono Pharmaceutical, Daiichi Sankyo, Amgen, Taiho Pharmaceutical, Takeda. Chugai Pharma, Nippon Kayaku, Eli Lilly Japan, Boehringer Ingelheim, Pfizer, and Bristol-Myers Squibb Japan, and grants from Daiichi Sankyo, Novartis, Chugai Pharma, Ono Pharmaceutical, Taiho Pharmaceutical, and Boehringer Ingelheim. Yukari Tsubata has received personal fees from MSD, AstraZeneca, Amgen, Daiichi Sankyo, Taiho Pharmaceutical, Takeda, Chugai Pharma, Eli Lilly Japan, Nippon Kayaku, Novartis, Pfizer, and Bristol-Myers Squibb, and grants from Pfizer and Ono Pharmaceutical. The other authors declare that they have no conflict of interest., (Copyright © 2024 [The Author]. Published by Elsevier B.V. All rights reserved.)

Techniques for triggering neural differentiation of embryonic and induced pluripotent stem cells into neural stem cells and neurons have been established. However, neural induction of mesenchymal stem cells, including dental pulp stem cells (DPSCs), has been assessed primarily based on neural-related gene regulation, and detailed studies into the characteristics and differentiation status of cells are lacking. Therefore, this study was aimed at evaluating the cellular components and differentiation pathways of neural lineage cells obtained via neural induction of human DPSCs. Human DPSCs were induced to neural cells in monolayer culture and examined for gene expression and mechanisms underlying differentiation using microarray-based ingenuity pathway analysis. In addition, the neural lineage cells were subjected to single-cell RNA sequencing (scRNA-seq) to classify cell populations based on gene expression profiles and to elucidate their differentiation pathways. Ingenuity pathway analysis revealed that genes exhibiting marked overexpression, post-neuronal induction, such as FABP7 and ZIC1, were associated with neurogenesis. Furthermore, in canonical pathway analysis, axon guidance signals demonstrated maximum activation. The scRNA-seq and cell type annotations revealed the presence of neural progenitor cells, astrocytes, neurons, and a small number of non-neural lineage cells. Moreover, trajectory and pseudotime analyses demonstrated that the neural progenitor cells initially engendered neurons, which subsequently differentiated into astrocytes. This result indicates that the aforementioned neural induction strategy generated neural stem/progenitor cells from DPSCs, which might differentiate and proliferate to constitute neural lineage cells. Therefore, neural induction of DPSCs may present an alternative approach to pluripotent stem cell-based therapeutic interventions for nervous system disorders., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)

The TP53 signature is considered a predictor of neoadjuvant chemotherapy (NAC) response and prognostic factor in breast cancer. The objective of this study was to confirm TP53 signature can predict pathological complete response (pCR) and prognosis in cohorts of breast cancer patients who received NAC in prospective studies. Development cohorts (retrospective [n = 37] and prospective [n = 216] cohorts) and validation cohorts (NAC administered prospective study cohorts [n = 407] and retrospective perioperative chemotherapy (PC)-naïve, hormone receptor (HrR)-positive cohort [PC-naïve_HrR+ cohort] [n = 322]) were used. TP53 signature diagnosis kit was developed using the development cohorts. TP53 signature predictability for pCR and the relationship between recurrence-free survival (RFS), overall survival (OS), and the TP53 signature were analyzed. The pCR rate of the mutant (mt) signature group was significantly higher than that of the wild-type (wt) signature group (odds ratio, 5.599; 95 % confidence interval = 1.876-16.705; P = 0.0008). The comparison of the RFS and OS between the HrR+ and HER2- subgroup of the NAC cohort and of the PC-naïve_HrR+ cohort indicated that the RFS and OS benefit of NAC was greater in the mt signature group than in the wt signature group. From post hoc analyses, the RFS and OS benefit from adding capecitabine to FEC+T as NAC might be observed only in the mt signature group. The TP53 signature can predict the pCR after NAC, and the RFS and OS benefit from NAC may be greater in the mt signature group than in the wt signature group., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ST reports honoraria from Ono, Chugai, Yakult Honsha, Taiho, Asahi Kasei Pharma, Eisai, Bristol-Myers Squibb and Eli Lilly; Prof. NM reports grants from Chugai, Eli Lilly, Astra Zeneca, Pfizer, Daiichi-Sankyo, MSD, Eisai, Novartis, Sanofi, Kyowa-Kirin, Nippon-Kayaku, Ono and Gilead Science, and honoraria from Chugai, Pfizer, Astra Zeneca, Eli Lilly and Daiichi-Sankyo, and Representative of a board of directors of JBCRG and Board of Directors of JBCS; MK reports honoraria from Pfizer, Daiichi-Sankyo, Astra Zeneca, Eli Lilly, Taiho, Kyowa-Kirin and Chugai; HI reports grants from Chugai, Daiichi-Sankyo and Astra Zeneca, and consulting fee from Daiichi-Sankyo, Chugai, Astra Zeneca, Eli Lilly, MSD, Pfizer and Gilead Science, and honoraria from Daiichi-Sankyo, Chugai, Astra Zeneca, Eli Lilly, MSD, Pfizer, Taiho and Kyowa-Kirin; TI reports honoraria from Pfizer, Kyowa-Kirin, Chugai, Daiichi-Sankyo, Astra Zeneca and Eli Lilly; TU reports grant from Eli Lilly, and honoraria from Chugai, Eisai, Astra Zeneca and Novartis; SO reports honoraria from Chugai, MSD, Nippon-Kayaku and Eli Lilly; HY reports grants from Eli Lilly and Eiken Kagaku; ET reports honoraria from Daiichi-Sankyo, Eli Lilly and Astra Zeneca; KA reports grants from Chugai, Eisai and Takeda, and consulting fee from Taiho, and honoraria from Chugai, Eisai, Astra Zeneca, Taiho, Novartis, Daiichi-Sankyo, Mochida, Ono, Pfizer, Eli Lilly, Terumo and Becton Dickinson; TT reports grants from Eli Lilly, Chugai, Eisai, Takeda, Kyowa-Kirin, Daiichi-Sankyo and Nippon-Kayaku, and honoraria from Daiichi-Sankyo, Pfizer, Novartis, Astra Zeneca, Chugai and Takeda; YY reports grants from Chugai, Kyowa-Kirin, Eisai, Daiichi-Sankyo, Nippon-Kayaku, Taiho, Takeda, Eli Lilly, Pfizer and Novartis, and honoraria from Astra Zeneca, Chugai, Kyowa-Kirin, Novartis, Eli Lilly, Pfizer, Daiichi-Sankyo, Nippon-Kayaku, Taiho, Eisai, Takeda, MSD, Sysmex and Exact Science, and participation on Advisory Board of Astra Zeneca, Chugai, Novartis, MSD, Eli Lilly, Pfizer and Daiichi-Sankyo, and member of the Board of Directors of JBCS and JBCRG; TY reports grants from Chugai, Taiho, Nippon-Kayaku and Kyowa-Kirin, and honoraria from Chugai, Eisai, Novartis, Taiho, Nippon-Kayaku, Astra Zeneca, Kyowa-Kirin, Pfizer, Eli Lilly and Daiichi-Sankyo; TY reports honoraria from Pfizer, Eli Lilly and Eisai; MT reports grants from Chugai, Takeda, Pfizer, JBCRG assoc., KBCRN assoc., Eisai, Eli Lilly, Daiichi-Sankyo, Astra Zeneca, Astellas, Shimadzu, Yakult, Nippon-Kayaku, AFI technology, Luxonus, Shionogi, GL Science and Sanwa Shurui, and honoraria from Chugai, Takeda, Pfizer, Kyowa-Kirin, Taiho, Eisai, Daiichi-Sankyo, Astra Zeneca, Eli Lilly, MSD, Exact Science, Novartis, Shimadzu, Yakult, Nippon-Kayaku, Devicore Medical Japan and Sysmex, and advisory board of Daiichi-Sankyo, Eli Lilly, BMS, Athenex Oncology, Bertis Terumo and Kansai Medical Net, and a member of the board of directors of JBCRG, KBCRN and OOTR, and chairman of the board of directors of JBCS, and associate editor of British Journal of Cancer, Scientific Reports, Breast Cancer Research and Treatment, Cancer Science, Frontiers in Women's Cancer, Asian Journal of Surgery and Asian Journal of Breast Surgery; TY reports grants from AC Medical, A2 Healthcare, ClinChoice, Japan Tabacco, Japan Media, Medidata Solutions, Ono, Kyowa-Kirin, Tsumura, Daiichi-Sankyo, Otsuka, Eisai, Solasia Pharma, Asahi Intecc, 3H Clinical Trial, Medrio, Nipro, Intellim, Welby, 3H Medi Solution, Baseconnect, Nobori, Puravida Technologies and Hemp Kitchen, and consulting fee from Public Health Research Foundation, EPS, Japan Tabacco, Medidata Solutions, Ono, Kowa, Chugai, Daiichi-Sankyo, Eisai, 3H Clinical Trial, Intellim, Astra Zeneca, Sonire Therapeutics, Seikagaku, Merck, Mebix and Nippon Boehringer Ingelheim, and advisory board of Incyte Bioscience; CI reports grants from Chugai, Asahi Kasei Pharma, Ono, Eli Lilly, Shionogi, Yakult, Otsuka, Sanofi, Merck, Astra Zeneca, Nippon Boehringer Ingelheim, Yansen, MSD, Sonia-Therapy, Taiho, Takeda, Daiichi-Sankyo, Bayer, Nippon-Kayaku, Tsumura, Kyowa-Kirin, Hitachi, Incyte, Ascent, Eisai, PRA Health Science, Novartis and Riken Genesis, and honoraria from Taiho, Merck, Eli Lilly, Bristol-Myers Squibb, Daiichi-Sankyo, Nippon-Kayaku, Nihon-Servier, M3, MSD, Novartis, Astra Zeneca, Ono, Sanofi, Chugai, Terumo, Asahi Kasei Pharma, Pfizer, Bayer, Incyte, Takeda and Kyowa-Kirin. All remaining authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Sacubitril/valsartan is an angiotensin receptor neprilysin inhibitor (ARNI) that inhibits the degradation of endogenous natriuretic peptides. Therefore, ARNIs may increase the efficacy of human atrial natriuretic peptide (hANP), a drug for acute heart failure, by mediating its pharmacological mechanism. This study was aimed at evaluating the effects of ARNIs on the pharmacological effects of hANP by using surrogate marker, such as urinary output, in patients with heart failure., Methods: In this multicenter retrospective cohort study, adult patients with heart failure who were taking angiotensin II receptor blockers (ARB) or ARNIs combined with hANP were enrolled. Information on basic characteristics, clinical laboratory data, medical history, and severity of cardiac insufficiency were collected from electronic medical records. The primary outcome was the change in adjusted fluid balance, calculated by IN-volume (mL/day) - OUT-volume (mL/day) / daily hANP dosage (μg)., Results: Ninety-two and 62 patients in the ARB + hANP and ARNI + hANP groups, respectively, were eligible for analysis. The adjusted fluid balance in the ARNI + hANP group was significantly lower than that in the ARB + hANP group (p = 0.001). After propensity score matching, 27 patients from each group were included. Similarly, there was a significant reduction in adjusted fluid balance in the ARNI + hANP group after propensity score matching (p = 0.026)., Conclusions: These findings suggest that ARNIs may enhance the efficacy of hANP and the combination of the two may be effective in the treatment of heart failure., (© 2024. The Author(s).)

Introduction: Recent reports have described the usefulness of carbon ion radiotherapy (CIRT) for inoperable sacral chordomas. However, its long-term local control rate needs to be improved. The present study identified the risk factors that affect the local relapse of sacral chordomas and the appropriate margins from the tumors., Methods: Forty-nine patients with sacral chordoma treated with CIRT between 2011 and 2022 were retrospectively analyzed. Factors predicting the risk of local recurrence were evaluated, including age, sex, tumor size, muscle invaded with tumor, and surgery before CIRT. To determine the appropriate margin, the distance between the clinical target volume (CTV) and the out-field recurrent lesions was analyzed., Results: The patients included 37 males and 12 females with a mean age of 67.1 years. A multivariate analysis showed that a tumor size >8 cm and invasion into the gluteus maximus muscle were significant risk factors with hazard ratios of 5.56 and 15.20 (p = 0.02 and 0.01), respectively. Out-field recurrence occurred in 13 cases, with 6, 3, and 4 relapses occurring in the muscle, bone, and both, respectively. The tumor occurred within 20 mm from the CTV in 60% of relapses in the muscles., Conclusion: The current study presented novel findings on CIRT for sacral chordomas, although there were several limitations, such as a short follow-up period to investigate slow-growth tumors and a small number of tumor specimens owing to inoperative cases. A tumor size >8 cm and invasion into the gluteus maximus muscle were shown to be risk factors for recurrence in the treatment of sacral chordoma with CIRT. Our findings further suggest that an additional 2-cm margin from the CTV in the muscle fiber direction is recommended during CIRT., (© 2024 S. Karger AG, Basel.)

A 61-year-old man presented to our hospital with a chief complaint of chronic cough. He was diagnosed with lung squamous cell carcinoma at clinical stage cT2aN3M1a. He received chemotherapy up to the fourth line, but both the primary tumor and lymph node metastases increased in size. Nivolumab, administered as the fifth line, resulted in a complete response (CR) that continued for 2 years and 8 months. Treatment was stopped due to the appearance of common terminology criteria for adverse events grade 1 pneumonitis. He was followed up without treatment for 3 years and 8 months, but a left supraclavicular fossa lymph node metastasis appeared. Retreatment with nivolumab was initiated, and the patient achieved CR again. One year and 6 months after retreatment, CR was maintained with nivolumab. This case represents a rare instance in which nivolumab yielded a significant response after a prolonged immune checkpoint inhibitor (ICI)-free interval. Our experience has shown that the long-term response to ICIs may deteriorate in the future. Therefore, retreatment with ICIs may be effective when the initial therapy is successful., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Continuous intravenous adenosine triphosphate (ATP) administration is the standard method for inducing maximal hyperemia in fractional flow reserve (FFR) measurements. Several cases have demonstrated fluctuations in the ratio of mean distal coronary pressure to mean arterial pressure (Pd/Pa) value during ATP infusion, which raised our suspicions of FFR value inaccuracy. This study aimed to investigate our hypothesis that Pd/Pa fluctuations may indicate inaccurate FFR measurements caused by insufficient hyperemia. We examined 57 consecutive patients with angiographically intermediate coronary lesions who underwent fractional flow reverse (FFR) measurements in our hospital between November 2016 and September 2018. Pd/Pa was measured after continuous ATP administration (150 μg/kg/min) via a peripheral forearm vein for 5 min (FFR A ); and we analyzed the FFR value variation in the final 20 s of the 5 min, defining 'Fluctuation' as variation range > 0.03. Then, 2 mg of nicorandil was administered into the coronary artery during continued ATP infusion, and the Pd/Pa was remeasured (FFR A+N ). Fluctuations were observed in 23 of 57 patients. The cases demonstrating discrepancies of > 0.05 between FFR A and FFR A+N were observed more frequently in the fluctuation group than in the non-fluctuation group (12/23 vs. 1/34; p < 0.0001). The discrepancy between FFR A and FFR A+N values was smaller in the non-fluctuation group (mean difference ± SD; -0.00026 ± 0.04636 vs. 0.02608 ± 0.1316). Pd/Pa fluctuation with continuous ATP administration could indicate inaccurate FFR measurements caused by incomplete hyperemia. Additional vasodilator administration may achieve further hyperemia when Pd/Pa fluctuations are observed., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

In May 2022, Hyogo Medical University Hospital introduced protocol-based pharmacotherapy management(PBPM), which is jointly planned by doctors and pharmacists, for certain cancer drug therapies. Colorectal cancer patients who underwent outpatient cancer chemotherapy in the Department of Lower Gastrointestinal Surgery from October to December 2021(before the introduction of PBPM)and from May to August 2022(after the introduction of PBPM)were retrospectively studied. The proportion of clinical examinations performed, number of prescription questions, and time taken by pharmacists to solve the prescription questions before and after the introduction of PBPM were compared. Additionally, the number of modifications made in the medical record by pharmacists on behalf of doctors in response to the prescription questions was assessed. The proportion of clinical examinations performed(clinical examinations actually performed/clinical examinations that should have been performed)improved from 93.2%(260/279)before to 98.8%(405/410)after the introduction of PBPM(p<0.001). The number of prescription questions decreased from an average of 64.7(±11.9)per month before to an average of 29.5(±3.4)per month after the introduction of PBPM. The average number of modifications made in the medical record by pharmacists on behalf of the doctors in response to the prescription questions was 25.8(±5.4)per month after the introduction of PBPM. There was no significant difference before and after the introduction of PBPM in regard to the median(interquartile range)time taken by pharmacists to solve the prescription questions (before PBPM: 1.88 minutes per case[1.70-2.28 minutes]; after PBPM: 1.71 minutes per case[1.61-2.06 minutes][p= 0.75]). The increased proportion of clinical examinations performed after the implementation of PBPM may have improved the safety of cancer drug management, and the decreased number of prescription questions is speculated to have led to a reduction in physician workload.

A 45-year-old man visited our hospital with a chronic cough and breathing difficulties. Chest computed tomography revealed diffuse granular shadows. Mycobacterium avium (M. avium) was cultured from bronchoalveolar lavage fluid (BALF). Surgical lung biopsy revealed non-necrotizing granulomas, and M. avium-specific PCR was positive in the tissue. M. avium was also cultured in a sample from the inlet of the patient's bathtub. Mycobacterium avium tandem repeat variable-number tandem-repeat loci (MATR-VNTR) analysis confirmed that the M. avium cultured from BALF and the bathtub inlet had identical allele profiles. The patient's symptoms and oxygenation improved while the patient was in hospital, presumably because of lack of ongoing exposure to M. avium. He was diagnosed with hot tub lung. We advised the patient to avoid bathing to avoid re-exposure. However, the patient was unwilling to follow this advice. Therefore, his bathtub and pipework were disinfected by heating them to over 70 °C. We confirmed that the disinfection has been successful by repeated culture of environmental samples. Three months after resuming bathtub use, the patient's symptoms resolved, and the pulmonary shadows seen on the initial radiography did not recur. For the treatment of hot tub lung, disinfection of M. avium complex in the environment should be considered and the environment should be monitored to confirm eradication., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Although dietary potassium restriction is an acceptable approach to hyperkalemia prevention, it may be insufficient for outpatients with chronic kidney disease (CKD). Most outpatients with CKD use community pharmacies owing to the free access scheme in Japan. The MieYaku-CKD project included a community pharmacist-led nutritional intervention for dietary potassium restriction, with the goal of determining its efficacy for patients' awareness of potassium restriction and serum potassium levels in outpatients with CKD. This was a five-community pharmacy multicenter prospective cohort study with an open-label, before-and-after comparison design. Eligible patients (n = 25) with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 received nutritional guidance from community pharmacists. The primary outcome was a change in serum potassium levels at 12 weeks post-intervention. The eligible patients' knowledge, awareness, and implementation of potassium restriction were evaluated using a questionnaire. The median value of serum potassium was significantly reduced from 4.7 mEq/L before to 4.4 mEq/L after the intervention [p < 0.001, 95% confidence interval (CI): 0.156-0.500], with no changes in eGFR (p = 0.563, 95% CI: -2.427-2.555) and blood urine nitrogen/serum creatinine ratio (p = 0.904, 95% CI: -1.793-1.214). The value of serum potassium had a tendency of attenuation from 5.3 to 4.6 mEq/L (p = 0.046, 95% CI: 0.272-1.114) in the eGFR < 30 mL/min/1.73 m2 group. A questionnaire revealed that after the intervention, knowledge and attitudes regarding dietary potassium restriction were much greater than before, suggesting that the decrease in serum potassium levels may be related to this nutritional guidance. Our findings indicate that implementing a dietary potassium restriction guidance program in community pharmacies is feasible and may result in lower serum potassium levels in outpatients with CKD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Asai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Postoperative temperature dysregulation affects the length of hospital stay and prognosis. This study evaluated the factors that influence the occurrence of fever in patients after aortic valve replacement surgery., Methods: Eighty-seven consecutive patients who underwent aortic valve replacement surgery were included. Patients' age, sex and body mass index; presence of diabetes mellitus; operation time; blood loss; blood transfusion volume; preoperative and postoperative laboratory findings; presence or absence of oral function management; and fever >38°C were retrospectively analysed through univariate and multiple logistic regression analyses., Results: Among the variables, only diabetes mellitus status was significantly associated with fever ⩾38°C. Postoperatively, patients with diabetes mellitus were significantly less likely to develop fever above 38°C and a fever rising to 38°C., Conclusions: This study shows that the presence of comorbid diabetes mellitus decreases the frequency of developing fever >38°C after aortic valve replacement surgery., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Background: Surgery is effective for extracranial internal carotid artery (EICA) aneurysms. However, the risk of cranial nerve injury associated with surgical repair, such as graft-assisted resection and extracranial-intracranial bypass techniques, is relatively high. Here, we report two cases of surgical treatment for EICA aneurysms and describe the surgical techniques and strategies to avoid cranial nerve injury., Methods: Two patients presented to our facility with an increasing cervical pulsatile mass and no neurological symptoms. Angiography showed a large aneurysm in the cervical internal carotid artery. Surgical treatment was performed to prevent rupture of the aneurysm. In both patients, the aneurysm was strongly attached to the vagus nerve. The aneurysm and vagus nerve were carefully dissected using a low-power bipolar (20 Malis; 3 watts), leaving connective tissue on the vagus nerve side., Results: The aneurysm was detached from the vagus nerve without injury. Based on intraoperative findings, one patient underwent clipping, and the other underwent aneurysmectomy and primary closure for aneurysm obliteration and angioplasty. Both patients were discharged without any cranial nerve dysfunction., Conclusion: The selection of a strategy based on intraoperative findings and low-power bipolar cutting is important for the treatment of extracranial carotid artery aneurysms to preserve cranial nerves., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Cigarette smoking during pregnancy is known to be associated with the incidence of attention-deficit/hyperactive disorder (ADHD). Recent developments in deep learning algorithms enable us to assess the behavioral phenotypes of animal models without cognitive bias during manual analysis. In this study, we established prenatal nicotine exposure (PNE) mice and evaluated their behavioral phenotypes using DeepLabCut and SimBA. We optimized the training parameters of DeepLabCut for pose estimation and succeeded in labeling a single-mouse or two-mouse model with high fidelity during free-moving behavior. We applied the trained network to analyze the behavior of the mice and found that PNE mice exhibited impulsivity and a lessened working memory, which are characteristics of ADHD. PNE mice also showed elevated anxiety and deficits in social interaction, reminiscent of autism spectrum disorder (ASD). We further examined PNE mice by evaluating adult neurogenesis in the hippocampus, which is a pathological hallmark of ASD, and demonstrated that newborn neurons were decreased, specifically in the ventral part of the hippocampus, which is reported to be related to emotional and social behaviors. These results support the hypothesis that PNE is a risk factor for comorbidity with ADHD and ASD in mice.

Para-aortic lymphadenectomy in gastric cancer surgery is a highly difficult surgical technique. In our hospital, we introduced robotic surgery in anticipation of the minimal invasiveness and advanced operability. We use a tunneling approach that progresses from the Treitz ligament to the peri-aorta. The transverse mesocolon is expanded with a tissue grasping clip, and the retroperitoneum is incised from the side of the Treitz ligament to approach the abdominal aorta and inferior vena cava. The No.16b1 and No.16a2 latero lymph nodes can be dissected with a good visual field. When it is judged that the visual field development of the No.16a2 inter-lymph nodes is poor, Kocher's operation is added. Since 2016, 18 patients have undergone para-aortic lymphadenectomy, 3 of whom underwent robotic surgery in our hospital. R0 resection was performed in all the cases, and 22.5 lymph nodes were dissected as No.16 lymph nodes(20.0 in all the cases included laparotomy). Although only a small number of patients were examined, robot-assisted para-aortic lymphadenectomy was considered safe.

A 75-year-old female, at her initial presentation, the tumor occupied her entire right breast, with a foul-smelling exudate. A biopsy revealed ER-positive, HER2-negative breast cancer, and CT revealed multiple lung metastases. Paclitaxel and fulvestrant were administered sequentially, the bleeding from the right breast mass stopped and the mass flattened. But, as the tumor progressed, the right breast mass re-enlarged and began to re-bleed. Therefore, hemostatic treatment with Mohs paste was performed in parallel with tamoxifen. Hemostatic effect was observed for a while, but she gradually became refractory to Mohs paste, necessitating frequent blood transfusions. It was decided to discontinue systemic drug therapy and consider palliative treatment, and to perform radiation therapy in parallel with Mohs paste treatment for the purpose of local control. After radiation therapy, the bleeding has completely stopped and blood transfusion has not to be required for 6 months. Although systemic drug therapy has been discontinued at the patient's request, she is still alive. While systemic drug therapy was discontinued, we were able to confirm the pure local control effect of combination of radiation therapy and Mohs paste.

Background: In recent years, the number of colorectal cancer in Europe and the U. S. has been decreasing, but there are increasing reports on the trend of early-onset colorectal cancer(EOCRC), which is a rare population with no established knowledge on its characteristics., Subjects and Methods: Of 3,501 colorectal cancer cases treated at our hospital between April 2011 and December 2021, those aged 39 years and younger were included., Results: There were 32 EOCRC cases, 11 males/21 females. The histological type was tub in 31 cases and por in 1 case. Postoperative adjuvant chemotherapy was administered in 14 patients, and 12 completed the scheduled course. Twenty nine patients underwent R0 resection, of which 6 patients had recurrence and 5 patients died of primary disease. In summary, although EOCRC patients were in good general condition and had a high completion rate of adjuvant chemotherapy, the relapse rate was high, suggesting the need for aggressive adjuvant chemotherapy and careful postoperative surveillance.

A 57-year-old woman experienced chest pain. A coronary angiogram revealed middle left anterior descending artery stenosis. Despite receiving adequate anti-hyperlipidemia treatment and undergoing percutaneous coronary intervention (PCI), she experienced angina and required PCI six more times for in-stent restenosis. As she had high lipoprotein (a) [LP-(a)] levels at the seventh PCI procedure, proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) was administered, and a reduction in the LP-(a) and low-density lipoprotein cholesterol (LDL-C) values was observed. She experienced no recurrence of angina for five years with PCSK9i treatment. PCSK9i can reduce not only LDL-C but also LP-(a) levels, resulting in cardiac event risk reduction.

Background: Carotid endarterectomy (CEA) and carotid artery stenting are common surgical interventions for internal carotid artery stenosis. Cerebral hyperperfusion syndrome (CHS) is a well-known complication of both procedures that can lead to intracranial hemorrhage and worsen clinical outcomes. Here, the authors report a rare case of non-aneurysmal subarachnoid hemorrhage (SAH) following CEA and review the relevant literature., Observations: A 70-year-old woman with hypertension and diabetes presented with progressive visual loss in the right eye and was diagnosed with ocular ischemic syndrome. Imaging revealed severe right cervical carotid artery stenosis. CEA was performed with no complications. Postoperatively, the patient's blood pressure was tightly controlled, with no evidence of CHS. However, an asymptomatic SAH was detected on postoperative day 7. Careful observation and blood pressure control were maintained. Since follow-up magnetic resonance imaging (MRI) showed no enlarging of the SAH and the patient was asymptomatic, she was discharged on postoperative day 15 with a modified Rankin scale score of 0., Lessons: This case highlights the potential occurrence of non-aneurysmal SAH as a rare complication of CEA, even in asymptomatic patients. Repeated postoperative MRI is necessary to detect such complications. It is crucial to carefully control blood pressure after CEA regardless of symptoms.

Lipopolysaccharide (LPS) derived from Porphyromonas gingivalis (P.g.), which causes periodontal disease, contributes to the development of non-alcoholic steatohepatitis (NASH). We investigated the role of Nrf2, an antioxidative stress sensor, in macrophages in the development of NASH induced by LPS from P.g. We generated macrophage-specific Nrf2 gene rescue mice (Nrf2-mRes), which express Nrf2 only in macrophages, using the cre/loxp system. Wild-type (WT) mice, whole body Nrf2-knockout (Nrf2-KO) mice, and Nrf2-mRes mice were fed a high-fat diet for 18 weeks, and LPS from P.g. was administered intraperitoneally for the last 6 weeks. Nrf2-KO mice developed severe steatohepatitis with liver inflammation and fibrosis compared with WT mice, and steatohepatitis was ameliorated in Nrf2-mRes mice. The mRNA expressions of Toll-like receptor (Tlr)-2, which activates inflammatory signaling pathways after LPS binding, and α-smooth muscle actin (αSma), which promotes hepatic fibrosis, were reduced in Nrf2-mRes mice compared with Nrf2-KO mice. The protein levels of LPS-binding protein in livers were increased in Nrf2-KO mice compared with WT mice; however, the levels were reduced in Nrf2-mRes mice despite similar numbers of F4/80 positive cells, which reflect macrophage/Kupffer cell infiltration into the livers. Nrf2 in macrophages ameliorates NASH through the increased hepatic clearance of LPS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chihara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Postoperative delirium (PD) is an acute brain dysfunction, with a particularly high incidence after cardiovascular surgery. Pharmacist-led interventions show limited evidence in attenuating PD in cardiovascular surgery. In this retrospective cohort study, we aimed to clarify the risk factors of PD for cardiovascular surgery focused on pharmacotherapy and elucidate the effect of pharmacist-led intervention on the PD attenuation rate based on protocol-based pharmaceutical management (PBPM). This study included 142 adult patients who underwent elective valve replacement or valvuloplasty. The risk factors for PD were investigated using multivariate logistic regression analysis. Taking risk factors into consideration, a protocol was developed to discontinue benzodiazepines prescriptions by ward pharmacists, and replace with ramelteon and suvorexant if all the following factors apply: 1) number of medications ≥ 6 drugs, 2) number of doses to take ≥ 4 times, and 3) regular use of benzodiazepines or insomnia. Subsequently, the PD rate was compared during a period of two years and 6 months between the pre-PBPM (n = 39) and post-PBPM (n = 62). The PD rate for elective valve replacement or valvuloplasty was 25% (35/142). The adjusted odds ratio for polypharmacy was 3.3 (95% confidence interval: 1.2-8.9, p = 0.016), suggesting that preoperative risk assessment may be essential for patients with polypharmacy. The PD rate significantly decreased to 13% (8/62) in the post-PBPM group compared with 33% (13/39) in the pre-PBPM group (p = 0.014). There was a significant decrease in benzodiazepines use in post-PBPM compared with pre-PBPM (p = 0.026); however, the rate of ramelteon and orexin receptor antagonists use increased by PBPM introduction (p < 0.001). Although the present PBPM still requires further modification, it is simple and potentially useful for pharmacists to assess the risk of patients undergoing any elective cardiovascular surgery., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Asai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Brain arteriovenous malformations (AVMs) usually manifest as hemorrhages or seizures. They rarely present with ischemic symptoms, especially in young patients. We present a case of an epileptogenic AVM that led to cerebral infarction due to paradoxical embolic occlusion of the middle cerebral artery (MCA) involving the main feeder of the lesion., Observations: A 35-year-old male had been suffering from AVM-associated epilepsy for 10 years and was scheduled for surgery. He suddenly developed right-sided hemiconvulsions followed by hemiparalysis and impaired consciousness. Computed tomography revealed no intracerebral hemorrhage, and symptoms were initially thought to indicate epilepsy and Todd's palsy. Because of his prolonged symptoms, he underwent magnetic resonance imaging, which revealed a large cerebral infarction due to occlusion of the MCA involving the main feeder of the AVM. The patient underwent AVM resection, and the partially thrombosed nidus was completely removed. Histopathological investigation revealed a fresh thrombus in totally occluded nonarteriosclerotic feeders. He had no atrial fibrillation; however, subsequent transesophageal echocardiography revealed a patent foramen ovale, suggesting a paradoxical embolism., Lessons: This case serves as a reminder that AVMs can present with considerable variability. Acute cerebral infarction should be considered a possible mechanism of seizures, even in patients with epileptogenic AVM.

To determine the intracellular behavior of p62, a marker of selective autophagy, in oral potentially malignant disorders (OPMDs). This retrospective study includes 70 patients who underwent biopsy or surgical resection and were definitively diagnosed with OPMDs. Immunohistochemical staining for p62, XPO1, p53, and ki67 was performed on all samples and positive cell occupancy was calculated. We statistically investigated the correlation between protein expression in OPMDs and the association between malignant transformation, clinicopathological characteristics, and occupancy. ki67 expression was negatively correlated with p62 expression in the nucleus ( p < 0.01) and positively correlated with p62 expression in the cytoplasm ( p < 0.01). For malignant transformation, the expression of p62 in the nucleus ( p = 0.03) was significantly lower in malignant transformation cases, whereas the expression of p62 in the cytoplasm ( p = 0.03) and the aggregation expression ( p < 0.01) were significantly higher. Our results suggest that the function of p62 is altered by its subcellular localization. In addition, defects in selective autophagy occur in cases of malignant transformation, suggesting that p62 is a potential biomarker of the risk of malignant transformation of OPMDs.

Oral ferric citrate hydrate (FCH) is effective for iron deficiencies in hemodialysis patients; however, how iron balance in the body affects iron absorption in the intestinal tract remains unclear. This prospective observational study (Riona-Oral Iron Absorption Trial, R-OIAT, UMIN 000031406) was conducted at 42 hemodialysis centers in Japan, wherein 268 hemodialysis patients without inflammation were enrolled and treated with a fixed amount of FCH for 6 months. We assessed the predictive value of hepcidin-25 for iron absorption and iron shift between ferritin (FTN) and red blood cells (RBCs) following FCH therapy. Serum iron changes at 2 h (ΔFe2h) after FCH ingestion were evaluated as iron absorption. The primary outcome was the quantitative delineation of iron variables with respect to ΔFe2h, and the secondary outcome was the description of the predictors of the body's iron balance. Generalized estimating equations (GEEs) were used to identify the determinants of iron absorption during each phase of FCH treatment. ΔFe2h increased when hepcidin-25 and TSAT decreased (-0.459, -0.643 to -0.276, p = 0.000; -0.648, -1.099 to -0.197, p = 0.005, respectively) in GEEs. FTN increased when RBCs decreased (-1.392, -1.749 to -1.035, p = 0.000) and hepcidin-25 increased (0.297, 0.239 to 0.355, p = 0.000). Limiting erythropoiesis to maintain hemoglobin levels induces RBC reduction in hemodialysis patients, resulting in increased hepcidin-25 and FTN levels. Hepcidin-25 production may prompt an iron shift from RBC iron to FTN iron, inhibiting iron absorption even with continued FCH intake.

Reflux esophagitis and gastric tube ulcer sometimes cause severe clinical problems in patients undergoing esophagectomy with gastric tube reconstruction. We previously reported that acidity in the gastric tube was decreased for 1 year after esophagectomy, and that lower acidity levels were associated with Helicobacter pylori (H. pylori) infection. However, the long-term changes in gastric acidity remain unknown. We aimed to investigate the long-term changes in gastric acidity after surgery. Eighty-nine patients who underwent esophagectomy with gastric tube reconstruction for esophageal cancer were analyzed. They underwent 24-hour pH monitoring, serum gastrin measurement, and H. pylori infection examination before surgery, at 1 month, 1 year, and 2 years after surgery. The gastric acidity at 1 month and 1 year after surgery was significantly lower than that before surgery (p=0.003, p=0.003). However, there was no difference in gastric acidity before and 2 years after surgery. The gas tric acidity in H. pylori-infected patients was significantly lower in comparison to non-infected patients at each time point (p=0.0003, p<0.0001, p<0.0001, p<0.0001, respectively). In H. pylori-infected patients, gastric acid ity was decreased for 1 year after surgery, and recovered within 2 years after surgery. However, no significant differences were observed in the acidity levels of non-infected patients during the 2-year follow-up period. The serum gastrin level increased after esophagectomy. The acidity levels in the gastric tube recovered within 2 years after surgery. Periodic endoscopy examination is recommended for early detection of acid-related disease, such as reflux esophagitis or gastric tube ulcer, after esophagectomy with gastric tube reconstruction.

This study investigated the effect of postoperative deep sedation after oral cancer reconstructive surgery on the occurrence of early postoperative pneumonia and early postoperative delirium. We obtained medical records of 108 consecutive patients who underwent microvascular reconstructive surgery at Tsukuba University Hospital for oral cancer between January 2013 and December 2021. Forty-six of them woke soon after surgery. Ten of these forty-six patients were restless and required immediate sedation within 3 h after surgery. The comparison between sedation group and no sedation group revealed early postoperative pneumonia in the no sedation group; however, sedation was not related to early postoperative delirium. The preoperative albumin levels of patients with postoperative pneumonia were significantly different ( p = 0.03) than those of patients without postoperative pneumonia. The performance status ( p = 0.02), preoperative albumin level ( p = 0.02), and age 75 years or older ( p = 0.02) were significantly associated with postoperative delirium. Restless patients and those who could not be sedated experienced delirium and pneumonia. The risk of pneumonia was increased for patients who were difficult to sedate.

Background: Fluorouracil infusion for 46±5h from the central venous(CV)port is required for mFOLFOX6, FOLFIRI, and FOLFOXIRI in patients with advanced colorectal cancer(CRC), followed by self-removal of the needle by patients. At our hospital, outpatients were instructed for self-removal of the needle, but the results were unsatisfactory. Therefore, instructions for self-removal of the needle from the CV port have been initiated at the patient ward since April 2019, making use of a hospital stay of 3 days., Patients: We retrospectively enrolled patients with chemotherapy-introduced advanced CRC from the CV port who received instructions for self-removal of the needle in the outpatient department and ward between January 2018 and December 2021., Results: Of all patients with advanced CRC, 21 received instructions at the outpatient department(OP)while 67 at patient ward(PW). Incidences of successful self-removal of the needle without the aid of others were similar: 47% in OP and 52% in PW(p=0.80). However, after several additional instructions involving their families, it was higher in PW than in OP(97.0 vs 76.1%, p=0.005). Incidences of successful self-removal of the needle without the aid of others in those aged≥75/<75, and≥65/<65 years were 0%/61.1%, and 35.4%/67.5%, respectively. OP was as a risk factor for failed self-removal of the needle in the logistic regression analysis(odds ratio: 11.19, 95%CI: 1.86- 67.30)., Conclusion: Repeated instructions involving patients' families during the hospital stay improved the incidence of successful self-removal of the needle. Involvement of patients' families from the beginning may effectively improve self- removal of the needle, particularly in the elderly patients with advanced CRC.

Background: Cerebral amyloid angiopathy is a common cause of subcortical hemorrhage in older adults. Although open hematoma removal may be performed for severe subcortical hemorrhage, its safety in patients with cerebral amyloid angiopathy has not been established, and postoperative rebleeding may occur. Therefore, this study aimed to investigate factors associated with postoperative rebleeding., Methods: Out of 145 consecutive patients who had undergone craniotomy for surgical removal of subcortical intracerebral hemorrhage between April 2010 and August 2019 at a single institution in Japan, we examined 109 patients with subcortical hemorrhage who met the inclusion criteria. After excluding 30 patients whose tissue samples were unsuitable for the study, the final study cohort comprised 79 patients., Results: Of the 79 patients, 50 (63%) were diagnosed with cerebral amyloid angiopathy (cerebral amyloid angiopathy group) and 29 (37%) were not diagnosed with noncerebral amyloid angiopathy (noncerebral amyloid angiopathy group). Postoperative rebleeding occurred in 12 patients (24%) in the cerebral amyloid angiopathy group and in 2 patients (7%) in the noncerebral amyloid angiopathy group. Preoperative prothrombin time-international normalized ratio and intraoperative bleeding volume were significantly associated with postoperative rebleeding in the cerebral amyloid angiopathy group (odds ratio = 42.4, 95% confidence interval = 1.14-1578; p = 0.042 and odds ratio = 1.005, 95% confidence interval = 1.001-1.008; p = 0.007, respectively)., Conclusions: Patients with cerebral amyloid angiopathy-related cerebral hemorrhage who are receiving antithrombotic therapy, particularly warfarin therapy, are at a high risk of postoperative rebleeding., Trial Registration: Registry and Registration Number of the study: 19-220, 2019/12/23, retrospectively registered., (© 2023. The Author(s).)

Microcephaly with pontine and cerebellar hypoplasia (MICPCH) syndrome is a neurodevelopmental disorder caused by the deficiency of the X-chromosomal gene CASK. However, the molecular mechanisms by which CASK deficiency causes cerebellar hypoplasia in this syndrome remain elusive. In this study, we used CASK knockout (KO) mice as models for MICPCH syndrome and investigated the effect of CASK mutants. Female CASK heterozygote KO mice replicate the progressive cerebellar hypoplasia observed in MICPCH syndrome. CASK KO cultured cerebellar granule (CG) cells show progressive cell death that can be rescued by co-infection with lentivirus expressing wild-type CASK. Rescue experiments with CASK deletion mutants identify that the CaMK, PDZ, and SH3, but not L27 and guanylate kinase domains of CASK are required for the survival of CG cells. We identify missense mutations in the CaMK domain of CASK derived from human patients that fail to rescue the cell death of cultured CASK KO CG cells. Machine learning-based structural analysis using AlphaFold 2.2 predicts that these mutations disrupt the structure of the binding interface with Liprin-α2. These results suggest that the interaction with Liprin-α2 via the CaMK domain of CASK may be involved in the pathophysiology of cerebellar hypoplasia in MICPCH syndrome.

Background: Gastroesophageal reflux disease (GERD) is a common complication after esophagectomy with gastric tube reconstruction. The GerdQ questionnaire was developed for diagnosing GERD in primary care patients. Its effectiveness in patients after esophagectomy remains unknown. In this study, we evaluated the usefulness of the GerdQ questionnaire for diagnosing GERD after esophagectomy for esophageal cancer., Materials and Methods: A total of 124 patients with esophageal cancer underwent right transthoracic esophagectomy with gastric tube reconstruction between January 2010 and December 2016. Esophagogastroduodenoscopy and 24-hour esophageal pH-metry were performed at 1 month, 1 year, and 2 years postoperatively. The GerdQ questionnaire was administered at the same postoperative time points. We assessed any correlation between the GerdQ scores and the endoscopy and pH-metry findings., Results: The incidence rates of GERD at 1 month, 1 year and 2 years post-surgery were 31.6%, 46.9%, and 49.2%, respectively. The GerdQ questionnaire showed 77% sensitivity and 56% specificity for diagnosing GERD at 2 years after esophagectomy when the cutoff point was 7. However, the optimal cutoff points were different at each postoperative time, and the scores showed some imbalance between sensitivity and specificity. Regurgitation may be a useful indicator, as the frequency of regurgitation was significantly higher in patients with GERD than in patients without GERD at 1 year (P = 0.046) and 2 years postoperatively (P = 0.048)., Conclusion: The GerdQ questionnaire is not a useful diagnostic tool for GERD in patients who have undergone esophagectomy for esophageal cancer.

Case: We reconstructed the knee extension mechanism using a novel procedure for a 16-year-old adolescent girl with osteosarcoma that invaded her femur, patella, and patellar tendon. The knee joint was replaced with a megaprosthesis, and the extension mechanism was reconstructed using artificial ligaments sandwiched with bone cement forming a patella. At the one-year follow-up, she could walk using a knee orthosis without crutches., Conclusions: Reconstruction of the knee extension mechanism after patellectomy remains challenging. Our new method achieved an acceptable knee function and is, therefore, useful for patients undergoing excision of the knee joint and extension mechanism., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C45)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Prognosis of pancreatic cancer is extremely poor due to recurrence in the early postoperative period. However, there are some reports that the prognosis for lung recurrence alone is relatively better than that of others. In this study, we report the cases of lung recurrence alone after radical resection of pancreatic cancer performed at our hospital. Among 255 cases of radical resection of pancreatic cancer performed at our hospital between July 2010 and August 2021, 6 cases in which the initial recurrence site of recurrence was lung alone were included in the study. The median age of the patients was 72 years (62-82), and there were 5 males and 1 female. Four patients had undergone pancreaticoduodenectomy and 2 patients underwent distal pancreatectomy. Four patients received adjuvant chemotherapy, 3 with S-1 and 1 with GEM. No patients underwent surgical resection for recurrence of lung metastasis, and all patients were treated with chemotherapy. The median time to recurrence was 351 days. As initial therapy after recurrence, 3 patients received GEM plus nab-PTX combination therapy and 3 patients received S-1. The median overall survival after recurrence was 1,979 days, and the 1-year and 3-year overall survival rates after recurrence were 100% and 100%, respectively. The prognosis of patients with recurrence of lung metastasis after surgery for pancreatic cancer at our hospital was similarly good as the previous reports.

The patient was a 48-year-old woman. At the time of consultation, a hard mass of 30 mm in size was palpated in area A of the right breast, and a firm mass of about 10 mm was seen in the umbilical region. Histological diagnosis of the breast mass was invasive ductal carcinoma. PET-CT scan showed accumulation in the right breast, as well as suspicion of umbilical metastasis and peritoneal dissemination, uterine mass, and left ovarian cancer. Since this is an atypical metastatic site for invasive ductal carcinoma of the breast, and the possibility of peritoneal dissemination due to gynecological cancer complications cannot be ruled out, resection of the umbilical mass and laparoscopy was performed. The review laparoscopy revealed no evidence of primary cancer in the uterine body or left ovary, and a white nodular lesion of suspected seeding in the peritoneum around the left ovary. The histology and immunostaining results of the umbilical mass and left peri-ovarian nodule both showed glandular luminal structures similar to those of the primary breast cancer, and the left peri-ovarian nodule was ER positive, GATA3 positive, and PAX8 negative, leading to the diagnosis of umbilical metastasis and peritoneal seeding derived from breast cancer. Umbilical metastasis is often referred to as Sister Mary Joseph's nodule in the case of visceral malignancies and is often associated with peritoneal dissemination and is often caused by invasive metastasis of peritoneal dissemination lesions on the dorsal side of the umbilical region. In this case, histological examination of the umbilical specimen showed no disseminated lesion on the peritoneal side, so it was not considered to be an invasive metastasis due to peritoneal dissemination.

Objectives  The bacteriological features of the frontal sinus mucosa may impose significant complications in neurosurgery, when breached unintentionally. This study aimed to investigate the bacterial flora in patients undergoing frontal craniotomy for cerebrovascular substrate surgery. Design  This is a single-center prospective study. Setting  When mucosal laceration occurred, the patients underwent frontal sinus reconstruction with mucosa reconstruction, preserving the nasofrontal duct. Participants  We enrolled eight consecutive patients who underwent bifrontal craniotomy associated with frontal sinus mucosa laceration. Main Outcome Measures  A portion of the mucosa was extracted during the reconstructive procedure and was sent for microbiological analysis. Results  None of the patients presented with the bacterial flora in the mucosal cultures. No patient experienced postoperative cerebrospinal fluid leakage or meningitis. One patient with a clinical history of chronic maxillary sinusitis presented with a subcutaneous abscess around the forehead at 9 months postoperatively. The patient rapidly recovered after receiving oral administration of antibiotics. Conclusions  Our findings demonstrated that the frontal sinuses were maintained in an aseptic environment in all cases. The results may encourage the development and wider use of transfrontal sinus approaches., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Serum magnesium (Mg) monitoring in patients with heart failure (HF) receiving magnesium oxide (MgO) is not adequately performed. Furthermore, the relationship between left ventricular function (LVF) and hypermagnesemia in HF is unknown. Here, we investigated the efficacy of serum Mg monitoring by protocol-based pharmaceutical management (PBPM) and the effect of LVF on hypermagnesemia. This protocol is for patients with an estimated glomerular filtration rate of <45 mL/min, receiving MgO, and admitted to the cardiology unit. The pharmacist includes the measurement of Mg when a blood test is ordered for a patient by their physician. Rates of serum Mg measurement and hypermagnesemia detection were compared at 2 years pre-PBPM (n = 88) and at 2 years post-PBPM (n = 55). LVF parameters and reported factors for hypermagnesemia were selected as explanatory factors on multivariate logistic regression. The measurement rate of serum Mg concentration significantly increased from 19.3% pre-PBPM to 80.0% post-PBPM (P < .001). The detection rate of hypermagnesemia also increased from 3.4% to 27.3%, respectively (P < .001). Our results suggest that serum Mg monitoring by PBPM may contribute to the early detection of hypermagnesemia and prevent its progression in HF. According to logistic regression, the adjusted odds ratio for hypermagnesemia with an exacerbation of HF was 9.57 (95% confidence interval: 1.594-57.477, P = .014), and the E/e' > 15, an index of reduced left ventricular diastolic capacity, was 6.46 (95% confidence interval: 1.291-32.364, P = .023). We propose that serum Mg monitoring should be performed during exacerbations of HF in patients with left ventricular diastolic dysfunction, with a pharmacist's assistance., (© 2022, The American College of Clinical Pharmacology.)

In the high-dose methotrexate (HD-MTX) treatment of patients with osteosarcoma, a dose-adjustment method using individual pharmacokinetic parameters (PK method) to optimize the concentration was developed in 2010. However, to the best of our knowledge, the clinical usefulness of the PK method has not been verified until now. In the present retrospective study, to assess the usefulness of the PK method, the achievement rate of an effective and safe concentration range was evaluated. A total of 43 patients with osteosarcoma who were administered HD-MTX therapy (43 first courses and 200 subsequent courses) were enrolled. The MTX dose in the first course was determined using a common method based on body surface area (BSA method); a total of 8-12 g/m 2 was administered as an initial dose for 1 h and a maintenance dose for 5 h. In the subsequent courses, loading and maintenance doses were calculated by the PK method based on the serum MTX concentration profile of the previous course. The effective target concentration during 1-6 h after the start of MTX administration was 700-1,000 µmol/l, whereas the target safe MTX level was less than 10, 1 and 0.1 µmol/l at 24, 48 and 72 h, respectively. Notably, the rate of achieving the effective target concentration was significantly higher when using the PK method as compared to that when using the BSA method. The achievement rate of the safe target concentration at 24, 48 and 72 h when using the PK method was significantly higher. Additionally, the incidence of abnormal laboratory values of aspartate aminotransferase and alanine aminotransferase was significantly lower when using the PK method. Therefore, the PK method was suggested to be very useful in HD-MTX therapy for patients with osteosarcoma., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Nagamine et al.)