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Antifibrotic agents have been widely used in patients with idiopathic pulmonary fibrosis (IPF). Long-term continuation of antifibrotic therapy is required for IPF treatment to prevent disease progression. However, antifibrotic treatment has considerable adverse events, and the continuation of treatment is uncertain in many cases. Therefore, we examined and compared the continuity of treatment between pirfenidone and nintedanib in patients with IPF. We retrospectively enrolled 261 consecutive IPF patients who received antifibrotic treatment from six core facilities in Gunma Prefecture from 2009 to 2018. Among them, 77 patients were excluded if the antifibrotic agent was switched or if the observation period was less than a year. In this study, 134 patients treated with pirfenidone and 50 treated with nintedanib were analyzed. There was no significant difference in patient background, discontinuation rate of antifibrotic treatment over time, and survival rate between the two groups. However, the discontinuation rate due to adverse events within one year of antifibrotic treatment was significantly higher in the nintedanib group than in the pirfenidone group (76% vs. 37%, p < 0.001). Furthermore, the discontinuation rate due to adverse events in nintedanib was higher than that of pirfenidone treatment throughout the observation period (70.6% vs. 31.2%, p = 0.016). The pirfenidone group tended to be discontinued due to acute exacerbation or transfer to another facility. The results of this study suggest that better management of adverse events with nintedanib leads to more continuous treatment that prevents disease progression and acute exacerbations, thus improving prognosis in patients with IPF.

Abstract Background Premenstrual syndrome (PMS) is a severe problem in women, and a well-balanced diet helps improve PMS symptoms. Eating disturbances are a major health problem in young women. Limited research has explored the correlation between eating behaviors and PMS symptoms in Japan. This study aimed to compare eating disturbances and the severity of PMS symptoms in college students. Methods This study was conducted among female college students using an online questionnaire. The questionnaire included basic information (age, height, and weight), PMS symptoms, and eating behaviors assessed using the Eating Attitudes Test 26. Results The proportion of those with PMS symptoms who were disturbed by PMS symptoms was significantly higher in the group with eating disturbance. Those who were affected by the physical symptoms of PMS had significantly higher scores on the subscales related to diet, bulimia and food preoccupation. Conclusion The results showed an association between PMS symptom severity and eating disturbance. The findings of this study indicate that individuals with eating disturbances may experience adverse effects on PMS symptoms, even in cases where weight is not at the extremes of excessive underweight or obesity.

Abstract Background Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia. We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity. Case presentation This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C > T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Behçet's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated. Conclusions Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C > T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions.

Abstract Background Risk factors for predicting pneumonitis during durvalumab consolidation after chemoradiotherapy (CRT) in locally advanced non‐small cell lung cancer (LA‐NSCLC) are still lacking. Extracellular vesicles (EVs) play a crucial role in intercellular communication and are potential diagnostic tools for various diseases. Methods We retrospectively collected predurvalumab treatment serum samples from patients treated with durvalumab for LA‐NSCLC, isolated EVs using anti‐CD9 and anti‐CD63 antibodies, and performed proteomic analyses. We examined EV proteins that could predict the development of symptomatic pneumonitis (SP) during durvalumab treatment. Potential EV‐protein biomarkers were validated in an independent cohort. Results In the discovery cohort, 73 patients were included, 49 with asymptomatic pneumonitis (AP) and 24 with SP. Of the 5797 proteins detected in circulating EVs, 33 were significantly elevated (fold change [FC] > 1.5, p

Introduction: Osimertinib (OSI), a third-generation EGFR tyrosine kinase inhibitor, is the standard treatment for patients with naive EGFR-mutant NSCLC. Nevertheless, information on how the mutation subtype affects disease progression after the failure of OSI treatment is scarce. Methods: We retrospectively reviewed patients with EGFR-mutant NSCLC who received OSI as a first-line treatment between April 2015 and December 2021. Results: This study included 229 patients. The objective response rate was 71%, with intracranial and extracranial response rates of 71% and 90%, respectively. The median progression-free survival was 23.3 mo (95% confidence interval [CI]: 19.6–26.7), and the median overall survival was 33.7 mo (95% CI: 31.3–58.6). Multivariate analysis revealed that the EGFR exon 21 L858R point mutation (L858R) (hazard ratio [HR] = 1.56, 95% CI: 1.04–2.34, p = 0.0328) and liver metastasis (HR = 2.63, 95% CI: 1.53–4.49, p = 0.0004) were significant predictors of progression-free survival in OSI treatment. The concomitant disease progression involving the central nervous system metastasis was significantly more common in patients with L858R (p = 0.048), whereas concomitant disease progression involving primary lesions was significantly more common in patients with exon 19 deletion mutation (p = 0.01). In addition, the probability of disease progression over time was higher for L858R compared with that for exon 19 deletion mutation, in patients with central nervous system metastasis (log-rank test, p = 0.027). Conclusions: The mutation subtype had an impact not only on the clinical outcome of the first-line OSI treatment but also on progression patterns after OSI treatment in patients with NSCLC harboring EGFR mutations.

Spinal astrocytoma is a rare neoplasm with discouraging prognosis, which accounts for 6–8 % of total intramedullary spinal tumors. As this is a rare entity, details of the clinical and molecular features have not been fully unraveled. We evaluated the radiologic findings, perioperative clinical presentation, histopathological features and treatment response in a single institution series of 37 consecutive cases of spinal astrocytomas (WHO grades 1 to 4).We identified 8, 16, 8, and 5 patients with grade 1, 2, 3, and 4 lesions, respectively, from 1988 to 2017. Peak ages were youngest in grade 1, followed in order by grades 4, 3 and 2. Whereas all cases of grade 1 and 4 enhanced with contrast, less than half of the cases of grade 2 tumors enhanced (44 %). Grade 3 tumors had a higher rate of multiplicity at presentation (50 %). A concomitant brain lesion at presentation was present in 14 % and 43 % of grade 2 and 3 lesions, respectively. Progression-free and overall survival were worse in grades 3 and 4 compared to grade 2 lesions but no significant difference was observed between grade 3 and 4. Many patients (16-of-36) experienced new neurological deficits postoperatively regardless of grade. Most patients (88 %) required postoperative rehabilitation, and 61 % were not discharged to home. Discharge destination closely correlated with age (p = 0.002). These clinical findings may be useful in understanding the clinical phenotype and improving the management of this rare disease.

Abstract Background It is still unclear whether patients with advanced non‐small cell lung cancer (NSCLC), with disease progression after initial immune checkpoint inhibitor (ICI) therapy, would benefit from ICIs readministration. Patients and Methods We retrospectively collected data from patients with advanced NSCLC who received ICI retreatment. Depending on the disease status at the discontinuation of the initial ICI therapy, the patients were divided into two groups: with disease progression (PD group) and without disease progression (Without PD group). Patients in the Without PD group were required to experience disease progression during the treatment‐free period. Efficacy was assessed by measuring the objective response rate (ORR) and progression‐free survival in retreatment (PFS‐R), while safety was assessed using the incidence of immune‐related adverse events (irAEs). Results 30 (46.7%) of 64 eligible patients were included in the PD group and 34 (53.1%) in the Without PD group. Patients in the Without PD group had better clinical outcomes than those in the PD group (ORR, 29.4% vs. 6.7%; p = 0.03, median PFS‐R, 4.1 months vs. 2.2 months, hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.36–1.04; p = 0.07). Multivariate Cox regression analysis showed that patients in the Without PD group had significantly longer PFS‐R than those in the PD group (HR 0.42, 95% CI, 0.21–0.85; p = 0.015). In terms of safety, 28.1% of patients observed irAEs during ICI retreatment, and the incidence rate of grade 3 or higher irAEs was 7.8%. Specifically, of the 28 patients who discontinued their initial ICI treatment because of irAEs, 35.7% developed irAEs, and 28.6% experienced relapsed irAEs during ICI retreatment. Conclusion Immune checkpoint inhibitor retreatment demonstrated efficacy in patients who discontinued initial ICI therapy for reasons other than disease progression. However, ICI retreatment was ineffective in patients with disease progression during the initial ICI treatment.

BackgroundDespite accumulating research on the molecular characteristics of meningiomas, no definitive molecularly targeted therapy for these tumors has been established to date. Molecular mechanisms underlying meningioma progression also remain unclear. Comprehensive genetic testing approaches can reveal actionable gene aberrations in meningiomas. However, there is still limited information on whether profiling the molecular status of subsequent recurrent meningiomas could influence the choice of molecular-targeted therapies.Case presentationWe report a case of meningioma with malignant progression and multiple recurrences. We performed matched tumor pair analysis using the Todai OncoPanel to investigate the possibility of additional standard treatments. The loss of several chromosomal regions, including NF2 and CDKN2A, which is associated with aggressive meningiomas, was considered a significant driver event for malignant progression. Using additional matched tumor pair analysis, mutations in TRAF7, ARID1A, and ERBB3 were identified as subclonal driver events at the time of recurrence. No genetic aberrations were found for which evidence-based targeted therapy was applicable. We also reviewed previous reports of molecular therapies in meningioma to discuss issues with the current molecular testing approach.ConclusionGene panel testing platforms such as the Todai OncoPanel represent a powerful approach to elucidate actionable genetic alterations in various types of tumors, although their use is still limited to the diagnosis and prediction of prognosis in meningiomas. To enable targeted molecular therapy informed by gene-panel testing, further studies including matched tumor pair analyses are required to understand the molecular characteristics of meningiomas and develop treatments based on genetic abnormalities.

Purpose: This study aims to examine the clinical autologous osteochondral grafts (AOG) outcomes for knee osteochondral diseases at operative ages >60 years, and to determine whether patients are able to sit straight in Japanese style after AOG. Methods: All patients who underwent AOG for knee osteochondral diseases between November 2001 and April 2018 were retrospectively identified. The inclusion criteria were AOG only without osteotomy, operative ages between 60 and 79 years, >2 years of follow-up, and involved femorotibial angle between 169° and 179° (normal alignment). Patients who underwent osteotomy to improve knee alignment and patients with inflammatory diseases such as rheumatoid arthritis were excluded. The patients’ knee symptoms and their clinical outcome were evaluated according to the criteria of the knee scoring system of the Japanese Orthopedic Association (JOA), International Knee Documentation Committee (IKDC) subjective score, and the ability of straight sitting in Japanese style. Results: This study enrolled 57 cases and 60 knee joints during the study period. The follow-up ratio was 85.1%. Moreover, 14 men and 43 women and 29 right and 31 left knee joints were included in this study. The mean operative age and mean follow-up period were 67.8 years (range 60-76 years) and 81.1 months (range 24-167 months), respectively. In addition, the study involved 30 cases and 32 knee joints (60s group), and 27 cases and 28 knee joints (70s group). Moreover, 34 cases and 36 knee joints had osteonecrosis (ON group), and 23 cases and 24 knee joints had cartilage injury (CI group). The IKDC subjective and JOA scores in both the 60s and 70s groups showed significant differences: 2 years after AOG ＞at the follow-up period, ＞at the preoperative period. The scores in both the CI and ON groups showed similar significant differences. Furthermore, 8.3% and 53.5% of the patients could sit straight in Japanese style at the preoperative period and 2 years after AOG, respectively. Conclusion: Even if the patient’s operative age was >60 years, the AOG only for their knee osteochondral diseases had good clinical outcomes, including the ability to sit straight in Japanese style. Level of Evidence: IV, Therapeutic case series Key words: autologous osteochondral grafts, aged patients, clinical outcome, knee joint, straight sitting in Japanese style

Abstract The major active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3), is known for its wide bioactivity in periodontal tissues. Although the exact mechanisms underlying its protective action against periodontitis remain unclear, recent studies have shown that 1,25D3 regulates autophagy. Autophagy is vital for intracellular pathogen invasion control, inflammation regulation, and bone metabolic balance in periodontal tissue homeostasis, and its regulation could be an interesting pathway for future periodontal studies. Since vitamin D deficiency is a worldwide health problem, its role as a potential regulator of autophagy provides new insights into periodontal diseases. Based on this premise, this narrative literature review aimed to investigate the possible connection between 1,25D3 and autophagy in periodontitis. A comprehensive literature search was conducted on PubMed using the following keywords (e.g., vitamin D, autophagy, periodontitis, pathogens, epithelial cells, immunity, inflammation, and bone loss). In this review, the latest studies on the protective action of 1,25D3 against periodontitis and the regulation of autophagy by 1,25D3 are summarized, and the potential role of 1,25D3-activated autophagy in the pathogenesis of periodontitis is analyzed. 1,25D3 can exert a protective effect against periodontitis through different signaling pathways in the pathogenesis of periodontitis, and at least part of this regulatory effect is achieved through the activation of the autophagic response. This review will help clarify the relationship between 1,25D3 and autophagy in the homeostasis of periodontal tissues and provide perspectives for researchers to optimize prevention and treatment strategies in the future.

Background/Aim: The safety and efficacy of laparoscopic total gastrectomy (LTG) for remnant gastric cancer (RGC) remains unclear. The purpose of this study was to compare the clinical outcomes of LTG with open total gastrectomy (OTG) for RGC. Patients and Methods: Twentytwo patients who underwent total gastrectomy for RGC were enrolled in this study. Results: LTG was carried out in seven patients, and OTG was performed in the remaining 15 patients. The mean operation time in the LTG group was longer than that in the OTG group. The estimated blood loss in the LTG group was less than that in the OTG group. No cases in the LTG group required open conversion. Postoperatively, the first meal and defecation were earlier in the LTG group than in the OTG group. The overall survival rates of the two groups were comparable. Conclusion: Laparoscopic total gastrectomy is a feasible surgical option for RGC. [ABSTRACT FROM AUTHOR]

Abstract Background In recent years, moderate physical activity has attracted the attention of experts and women as a way to cope with premenstrual syndrome (PMS). Studies investigated the effects of exercise on PMS, but only a few reports focused on the relationship between physical activity, which included not only exercise but also routine bodily movements, and PMS. Therefore, the present study investigated the relationship between the amount of physical activity and PMS symptoms among sexually mature female students. Methods A total of 381 female university students in Japan were surveyed using a paper or web-based questionnaire with the same content. The questionnaire consisted of basic information, PMS symptoms, and physical activity based on the International Physical Activity Questionnaire (IPAQ). Participants were divided into two groups (≥ 3000 The Metabolic Equivalent of Task (MET)-minutes/week and

Background: Shoulder range of motion (ROM) is one of the most important indicators of shoulder disease severity, function, and physical assessment. A universal goniometer (UG) was used as a gold standard for ROM measurement. Recently, smartphone applications for ROM measurement have attracted attention as alternatives to UG. This study aimed to investigate the validity and reliability of active ROM measurements using a smartphone application goniometer that can be used by patients in a standing position. Methods: The dominant shoulders of 19 healthy participants were included in the study. The 2 observers who were physical therapists used the UG, whereas the participants used a smartphone application goniometer to measure the shoulder ROM. A recorder, who is a physical therapist independent of the observer and participant, read and recorded the shoulder ROM measurements. The order of the measurement movements and devices used was randomized. Results: Agreement between the smartphone application goniometer and UG (percentage of participants for whom the difference between the UG and application measurements was within ±20% of the mean of the goniometer and application measurements) ranged between 42% and 100%. The intraclass correlation coefficient values (3, 1) for the agreement between the smartphone application goniometer and UG was between 0.72 and 0.97, showing significant and approximately perfect correlations. Conclusion: High agreement with the UG showed excellent validity, indicating that the smartphone application goniometer used by the participants in the standing position is an excellent method and instrument. The results suggest a simpler, more reliable, practical, and inexpensive method for measuring ROM required for telerehabilitation.

Background:. Arthroscopic partial trapeziectomy with suture-button suspensionplasty was developed for the surgical treatment of thumb carpometacarpal arthritis. However, the relationship between clinical results and radiographic evidence is unclear. Methods:. The authors retrospectively reviewed 33 consecutive patients who underwent arthroscopic partial trapeziectomy with suture-button suspensionplasty for thumb carpometacarpal arthritis between 2016 and 2021. Clinical and radiographic outcomes were recorded, and the correlations between them were evaluated. Results:. The average patient age at surgery was 69 years. Patient radiologic evidence was Eaton stage Ⅱ in three thumbs, Ⅲ in 25 thumbs, and Ⅳ in five thumbs. The average trapezial space ratio (TSR) was 0.36 immediately after the operation but declined to 0.32 after 6 months. In contrast, the average joint subluxation was reduced to 0.005 immediately after the operation compared with 0.28 before, and was maintained at 0.04 at final follow-up. A statically significant correlation was detected between grip strength and TSR (P = 0.03), and between pinch strength and TSR (P = 0.02). A significant correlation was detected between TSR and trapezium height (P = 0.0215), which remained after partial trapeziectomy. No correlation was detected between rope position and other clinical or radiographic scores. Conclusions:. Suture-button can have an effect on the medialization of the first metacarpal base. Excessive trapeziectomy can result in functional deficiency of the thumb through metacarpal subsidence, which potentially causes loss of grip and pinch strength.

Key Clinical Message Malignant peritoneal mesothelioma, a rare and poor prognosis disease, is seldom treated surgically, especially for recurrence. However, early diagnosis and aggressive treatment of primary and recurrent tumors can achieve long‐term patient survival. Abstract Malignant peritoneal mesothelioma (MPM) is a rare and aggressive tumor, and rarely indicated for surgery, especially for recurrence. In the present case, we report a rare case who could survive long‐term after two surgeries in 4 years for MPM.

Introduction: Immune checkpoint inhibitors (ICIs) induce long-term, durable responses in patients with advanced NSCLC. Nevertheless, these responses are limited to a few patients, and most responders have disease progression. The purpose of this study was to determine the differences in clinical factors and blood drug concentrations between long-term responders (LTRs) and non-LTRs. Methods: We retrospectively analyzed consecutive patients with advanced NSCLC who received antiprogrammed cell death protein 1 (PD-1) inhibitor monotherapy (nivolumab) from December 22, 2015, to May 31, 2017. Patients who obtained a clinical benefit for more than 6 months were referred to as “responders”; among these, individuals who had a durable response for more than 2 years were defined as “LTRs.” Those with a clinical benefit for less than 2 years were defined as “non-LTRs.” Results: A total of 212 patients received anti–PD-1 inhibitor monotherapy. The responders accounted for 35% (75 of 212) of the patients. Of these, 29 (39%) were LTRs and 46 (61%) were non-LTRs. The overall response rate and median tumor shrinkage in the LTR group were significantly higher than those in the non-LTR group (76% versus 35%, p < 0.0001, and 66% versus 16%, p < 0.001, respectively). The groups had no significant difference in PD-L1 expression and serum drug concentration at 3- and 6-month post-treatment initiation. Conclusions: Significant tumor shrinkage was associated with a long-term response to an anti–PD-1 inhibitor. Nevertheless, the PD-L1 expression level and pharmacokinetic profile of the inhibitor could not be used to predict the durable response among the responders.

Dental caries are an oral infectious disease that can affect human health both orally and systemically. It remains an urgent issue to establish a novel antibacterial method to prevent oral infection for a healthy life expectancy. The aim of this study was to evaluate the inhibitory effects of novel iron chelators, super-polyphenols (SPs), on the cariogenic bacterium Streptococcus mutans, in vitro. SPs were developed to reduce the side effects of iron chelation therapy and were either water-soluble or insoluble depending on their isoforms. We found that SP6 and SP10 inhibited bacterial growth equivalent to povidone-iodine, and viability tests indicated that their effects were bacteriostatic. These results suggest that SP6 and SP10 have the potential to control oral bacterial infections such as Streptococcus mutans.

Stereotactic frame-based brain tumor biopsy (SFB) is a potent diagnostic tool considering its minimal invasiveness, though its diagnostic power and safety for brainstem lesions remain to be discussed. Here, we aimed to examine the usefulness of SFB for brainstem tumors. Twenty-two patients with brainstem tumors underwent 23 SFBs at our institution during 2002–2021. We retrospectively analyzed patient characteristics, tumor pathology, surgical procedures, and outcomes, including surgery-related complications and the diagnostic value. Seven (32%) tumors were located from the midbrain to the pons, eleven (50%) in the pons only, and four (18%) from the pons to the medulla oblongata. The target lesions were in the middle cerebellar peduncles in sixteen procedures (70%), the cerebellum in four (17%), the inferior cerebellar peduncles in two (9%), and the superior cerebellar peduncles in one (4%). A definitive diagnosis was made in 21 patients (95%) at the first SFB. The diagnoses were glioma in seventeen (77%) cases, primary central nervous system lymphoma in four (18%), and a metastatic brain tumor in one (5%). The postoperative complications (cranial nerve palsy in three [13%] cases, ataxia in one [4%]) were all transient. SFB for brainstem tumors yields a high diagnostic rate with a low risk of morbidity.

Background and Purpose To assess the long-term outcomes of intracranial dural arteriovenous fistula (DAVF) treated with stereotactic radiosurgery (SRS) alone or embolization and SRS (Emb-SRS) and to develop a grading system for predicting DAVF obliteration. Methods This multi-institutional retrospective study included 200 patients with DAVF treated with SRS or Emb-SRS. We investigated the long-term obliteration rate and obliteration-associated factors. We developed a new grading system to estimate the obliteration rate. Additionally, we compared the outcomes of SRS and Emb-SRS by using propensity score matching. Results The 3- and 4-year obliteration rates were 66.3% and 78.8%, respectively. The post-SRS hemorrhage rate was 2%. In the matched cohort, the SRS and Emb-SRS groups did not differ in the rates of obliteration (P=0.54) or post-SRS hemorrhage (P=0.50). In multivariable analysis, DAVF location and cortical venous reflux (CVR) were independently associated with obliteration. The new grading system assigned 2, 1, and 0 points to DAVFs in the anterior skull base or middle fossa, DAVFs with CVR or DAVFs in the superior sagittal sinus or tentorium, and DAVFs without these factors, respectively. Using the total points, patients were stratified into the highest (0 points), intermediate (1 point), or lowest (≥2 points) obliteration rate groups that exhibited 4-year obliteration rates of 94.4%, 71.3%, and 60.4%, respectively (P

Abstract Background Multiple deep organ abscesses associated with Staphylococcus aureus bloodstream infection (SAB) have a high mortality rate, requiring rapid removal or drainage of infective foci with long-term appropriate antimicrobial therapy. Cases in which infective foci cannot be completely removed are challenging for their management. Case presentation A 77-year-old man developed multiple deep organ abscesses associated with SAB. The left anterior chest subcutaneous abscess continued into the right anterior mediastinum and had extensively destroyed the sternum. Necrotizing fasciitis was observed in the bilateral feet. The anterior mediastinum abscess was drained percutaneously, and the chest wall abscess was incised cautiously without causing an external pneumothorax. On the next day, right-sided pyothorax had developed, requiring pleural drainage. On the third day, debridement of anterior chest wall abscess followed by concurrent thoracoscopic pleural curettage and debridement of bilateral feet were performed. Thorough sternal debridement was not performed, considering the risk of respiratory failure due to the sternal defects. On the 24th day, sternum debridement and incisional drainage of sciatic rectus fossa abscess, which had been present since the time of admission, were performed to control persistent infection. The caudal half of the sternal body was resected, leaving the costal cartilage attachments. The general condition further improved without postoperative respiratory failure after the second surgery, leading to a transfer to the general ward on the 43rd day. Conclusions We successfully treated the severe multiple deep organ abscesses, including a mediastinum abscess with sternum destruction, by repeated removal of the infective foci while avoiding respiratory failure due to excessive debridement of the anterior chest wall, including the sternum.

Background: The Burkholderia cepacia complex (Bcc) is an opportunistic pathogen in humans and animals. Deep pyoderma caused by these bacteria in dogs has been previously reported. This case series aims to describe contrasting treatment responses in Bcc-related deep pyoderma in two dogs, a male and a female. Case Description: Both patients had a history of immune-mediated polyarthritis managed with oral ciclosporin and prednisolone. Their skin lesions were multifocal, irregular, erythematous to haemorrhagic, alopecic papules, plaques, and nodules, with extensive crusting, draining tracts, and ulceration. Cytological findings revealed a marked inflammatory response consisting of non-degenerative and degenerative neutrophils and macrophages, with moderate to abundant intracellular and extracellular Bcc. Ciclosporin and prednisolone were stopped in case 2 after diagnosis. However, it was challenging to stop the regimen in case 1 because of recurrence of immune-mediated polyarthritis and the onset of iatrogenic hypoadrenocorticism. Case 1 did not achieve remission for approximately 66 weeks even with seven protocols because of multiple relapses, whereas it took only three weeks to achieve remission in case 2 while using one drug. Conclusion: For deep pyoderma with extensive lesions in immunosuppressed patients, one should consider infection with Bcc. Therefore, immunosuppressants should promptly be reduced in such patients, and then, intensive antimicrobial therapy may achieve remission.

Background: Pemetrexed is used for the chemotherapy of advanced thymoma. Exceptional responses of thymoma to pemetrexed treatment are not frequently observed. The underlying genetic mechanism of the exceptional responses remains unclear. We used whole-exome sequencing to explore the specific genomic aberrations that lead to an extreme and durable response. Methods: Whole-exome sequencing using NovaSeq6000 (150 bp paired-end sequencing) was performed on nine formalin-fixed paraffin-embedded tissues from patients with advanced thymomas treated with pemetrexed (two exceptional responders and seven typical responders). Results: We identified 284 somatic single-nucleotide variants (SNVs; 272 missense, 8 missense/splice-site, 3 stop-gain, and 1 stop-gain/splice-site), 34 insertions and deletions (Indels; 33 frameshift and one splice region), and 21 copy number variations (CNVs; 15 gains and six losses). No difference in the number of SNVs variants and distribution of deleterious Indels was observed between the exceptional and typical responders. Interestingly, arm-level chromosomal CNVs (15 gains and six losses) were detected in four patients, including an exceptional responder. The highest number of arm-level CNVs was observed in an exceptional responder. Conclusion: Exceptional responders to pemetrexed for metastatic thymomas may be characterized by arm-level CNVs. Further, whole-genome and RNA sequencing studies should be performed.

The combination effects of smoking (SMK) and hyperuricemia (HU) on renal arteriolosclerosis in patients with IgA nephropathy remain unknown. We examined the cross-sectional association between smoking (current or former) and renal arteriolar hyalinosis and wall thickening with or without HU [uric acid (UA) level ≥ 7 and ≥5 mg/dL in men and women] in 87 patients with IgA nephropathy who underwent renal biopsy. Arteriolar hyalinosis and wall thickening were assessed by the semiquantitative grading of arterioles. The SMK/HU subgroup showed the highest indices for hyalinosis and wall thickening, followed by the non-SMK/HU, SMK/non-HU, and non-SMK/non-HU subgroups. Multiple logistic analysis showed that SMK/HU, but not SMK/non-HU, was significantly associated with an increased risk of higher-grade renal arteriolar wall thickening. However, this did not occur with hyalinosis compared to non-SMK/non-HU. The adjusted odds ratio (95% confidence interval, p value) for SMK/HU was 12.8 (1.36–119, p < 0.05) for wall thickening. An association between SMK and renal arteriolar wall thickening might be prevalent only among patients with HU and in patients with IgA nephropathy. Further prospective studies are needed to determine whether patients with HU and SMK history exhibit rapid eGFR deterioration.

Abstract Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (Exon20ins) account for 4–12% of all EGFR mutations in non-small cell lung cancer (NSCLC) patients. Data on the differences in clinical characteristics between patients with Exon20ins and major mutations (M-mut) such as exon 19 deletion and L858R are limited. We retrospectively reviewed advanced NSCLC patients with EGFR mutations, who were treated with systemic therapy between January 2011 and December 2019. We identified 23 patients with Exon20ins and 534 patients with M-mut. In Exon20ins patients, the median age was 60 (range 27–88) years, and females and never-smokers were predominant. Clinical characteristics were similar in the two groups. In Exon20ins patients, 17 patients received platinum doublet as first-line therapy, and the overall response rate (ORR) and median progression-free survival (mPFS) were 11.8% and 8.9 months. Additionally, seven patients received conventional EGFR-tyrosine kinase inhibitors (TKIs), and eight patients anti-PD-1 antibodies in any-line therapy. ORR and mPFS of EGFR-TKIs and anti-PD-1 antibodies were 0%, 2.2 months and 25%, 3.1 months, respectively. Overall survival was significantly shorter in Exon20ins patients than in M-mut patients (29.3 vs. 43.4 months, p = 0.04). The clinical outcomes in Exon20ins patients were not satisfactory compared to M-mut patients.

Abstract The Keras deep learning framework is employed to study MRI brain data in a preliminary analysis of brain structure using a convolutional neural network. The results obtained are matched with the content of personality questionnaires. The Big Five personality traits provide easy differentiation for dividing personalities into different groups. Until now, the highest accuracy obtained from the results of personality prediction from the analysis of brain structure is about 70%. Although there is still no effective evidence to prove a clear relationship between brain structure and personality, the obtained results could prove helpful in understanding the basic relationship between brain structure and personality characteristics.

Objectives: This study aimed to examine the factors for reducing monetary loss due to presenteeism by using a tailored healthcare web-application among office workers with chronic neck pain. Methods: The study was singlearm pre-post comparison study using secondary data of 130 Japanese office workers with chronic neck pain who used a tailored healthcare web-application (web-app) over 12 weeks. This data was obtained from BackTech Inc. (Kyoto, Japan), which manages the healthcare web-app. The primary outcome measure was the monetary loss due to presenteeism based on the quality and quantity method. Secondary outcome measures were intensity of physical symptoms measured by the Visual Analog Scale, frequency of web-app use obtained from the database, and the risk of depression score assessed by the Depression and Suicide Screen. Results: Eighty-six participants were included in the complete-case analysis. Monetary loss due to presenteeism and the risk of depression reduced, while physical symptoms improved significantly ( p< 0.01) after using the web-app. After covariate adjustment, decrease in neck pain intensity (β = 0.25, confidence interval = 2.34 to 32.66) and high frequency of web-app use (β = −0.24, confidence interval = −10.29 to − 0.63) were significantly associated with a reduction in monetary loss due to presenteeism. Conclusion: Neck pain intensity and frequency of web-app use may be important factors for reducing monetary loss due to presenteeism among office workers with chronic neck pain who used a tailored health care web-app.

BackgroundCOVID-19 vaccines are considered one of the most effective ways for containing the COVID-19 pandemic, but Japan lagged behind other countries in vaccination in the early stages. A deeper understanding of the slow progress of vaccination in Japan can be instructive for COVID-19 booster vaccination and vaccinations during future pandemics. ObjectiveThis retrospective study aims to analyze the slow progress of early-stage vaccination in Japan by exploring opinions and sentiment toward the COVID-19 vaccine in Japanese tweets before and at the beginning of vaccination. MethodsWe collected 144,101 Japanese tweets containing COVID-19 vaccine-related keywords between August 1, 2020, and June 30, 2021. We visualized the trend of the tweets and sentiments and identified the critical events that may have triggered the surges. Correlations between sentiments and the daily infection, death, and vaccination cases were calculated. The latent dirichlet allocation model was applied to identify topics of negative tweets from the beginning of vaccination. We also conducted an analysis of vaccine brands (Pfizer, Moderna, AstraZeneca) approved in Japan. ResultsThe daily number of tweets continued with accelerating growth after the start of large-scale vaccinations in Japan. The sentiments of around 85% of the tweets were neutral, and negative sentiment overwhelmed the positive sentiment in the other tweets. We identified 6 public-concerned topics related to the negative sentiment at the beginning of the vaccination process. Among the vaccines from the 3 manufacturers, the attitude toward Moderna was the most positive, and the attitude toward AstraZeneca was the most negative. ConclusionsNegative sentiment toward vaccines dominated positive sentiment in Japan, and the concerns about side effects might have outweighed fears of infection at the beginning of the vaccination process. Topic modeling on negative tweets indicated that the government and policy makers should take prompt actions in building a safe and convenient vaccine reservation and rollout system, which requires both flexibility of the medical care system and the acceleration of digitalization in Japan. The public showed different attitudes toward vaccine brands. Policy makers should provide more evidence about the effectiveness and safety of vaccines and rebut fake news to build vaccine confidence.

Introduction: Lorlatinib (LOR) or pemetrexed-based chemotherapy (PEM) is the standard treatment after failure of a second-generation ALK tyrosine kinase inhibitor, such as alectinib, in patients with ALK-positive NSCLC. Nevertheless, there have been few data on the clinical outcomes of these treatments after alectinib failure. Methods: We retrospectively analyzed patients with ALK-rearranged NSCLC who received LOR (LOR group) or PEM (PEM group) as post-treatment after alectinib failure between December 2012 and August 2020. Results: Among 90 patients who experienced disease progression during alectinib treatment, 38 of them received either PEM (n = 22) or LOR (n = 16) as subsequent treatment. The objective response rate and the median progression-free survival were similar in the PEM and LOR groups (objective response rate: 45% versus 44%, p = 0.92; median progression-free survival: 6.9 mo versus 6.2 mo, p = 0.83, respectively). Disease progression during treatment occurred in 22 patients with PEM and 14 patients with LOR. The central nervous system (CNS) was the most common site of progression in both groups. In patients without CNS metastasis at baseline, the cumulative incidence rate of CNS progression was lower over time in the LOR group compared with the PEM group (p = 0.045), whereas in patients with CNS metastasis at baseline, there were no significant differences in cumulative incidence rate of CNS progression between both groups (p = 0.43). Conclusions: Clinical outcomes of PEM and LOR after failure of alectinib were similar in patients with ALK-positive NSCLC.

The surgical resection of intraventricular meningiomas (IVMs) remains challenging because of their anatomically deep locations and proximity to vital structures, resulting in non-negligible morbidity and mortality rates. Stereotactic radiosurgery (SRS) is a safe and effective treatment option, providing durable tumor control for benign brain tumors, but its outcomes for IVMs have rarely been reported. Therefore, the goal of the present study was to evaluate the SRS outcomes for IVMs at our institution. This retrospective observational study included 11 patients with 12 IVMs with a median follow-up period of 52 months (range, 3–353 months) treated with SRS using the Leksell Gamma Knife. Nine (75%) tumors were located in the trigone of the lateral ventricle, two (17%) in the body of the lateral ventricle, and one (8%) in the third ventricle. Tumor control was achieved in all cases, and seven (55%) decreased in size. Post-SRS perifocal edema was observed in four (37%; three asymptomatic and one symptomatic but transient) patients, all of which were resolved by the last follow-up. SRS appears to provide safe and excellent tumor control for IVMs. A longer follow-up with a larger number of cases is desired for a more solid conclusion.