Solid tumours showing oligoprogression to immune checkpoint inhibitors have the potential for abscopal effects.

PURPOSE: Given the uncertainty surrounding the abscopal effect (AE), it is imperative to identify promising treatment targets. In this study, we aimed to explore the incidence of AE when administering radiotherapy to patients with oligoprogressive solid tumours while they are undergoing treatment with immune checkpoint inhibitors (ICIs). MATERIALS AND METHODS: In this multicentre prospective observational study, oligoprogressive disease was defined as a < 20% increase in lesions compared to > 2 months before enrolment. We enrolled patients who requested radiotherapy during the ICI rest period between 2020 and 2023. AE was considered present if ≥ 1 non-irradiated lesion decreased by ≥ 30% before the next line of systemic therapy started. RESULTS: Twelve patients were included in this study; the common primary lesions were in the lungs (four patients) and kidneys (three patients). AEs were observed in six (50%) patients, with a median time to onset of 4 (range 2-9) months after radiotherapy. No significant predictors of AEs were identified. Patients in the AE group had a significantly better 1-year progression-free survival (PFS) rate than those in the non-AE group (p = 0.008). Two patients from the AE group were untreated and progression-free at the last follow-up. Four (33%) patients experienced grade 2 toxicity, with two cases attributed to radiotherapy and the other two to ICI treatment. No grade 3 or higher toxicities were observed in any category. CONCLUSION: Patients with oligoprogressive disease may be promising targets with potential for AEs. AEs can lead to improved PFS and, in rare cases, to a certain progression-free period without treatment. Irradiating solid tumours in patients with oligoprogressive disease during immune checkpoint inhibitor therapy may be a promising target with the potential for abscopal effects (AEs). AEs can lead to improved progression-free survival and, in rare cases, to a certain progression-free period without treatment.

Factors Associated with Reclosure of Posterior Capsule Aperture by Flat Opacifications with Pearls after Nd:YAG Laser Posterior Capsulotomy.

In this retrospective case series, we investigated factors associated with posterior capsule aperture (PCA) reclosure following neodymium-yttrium aluminum garnet (Nd:YAG) laser posterior capsulotomy. The study encompassed patients who underwent cataract surgery with intraocular lens (IOL) implantation or a combined vitrectomy, cataract surgery, and IOL implantation between 2009 and 2022. PCA reclosure was observed in 22 eyes of 17 patients: 45% (10 eyes) underwent the triple procedure, and 55% (12 eyes) received cataract surgery with IOL implantation. In our clinic, 14% of patients were given IOLs with a 4% water content, while 73% (13 eyes) of those experiencing PCA reclosure had IOLs with a 4% water content. The mean interval between Nd:YAG capsulotomies was notably shorter than that between the initial cataract surgery and the first Nd:YAG laser capsulotomy. We also identified five stages of PCA reclosure progression. In conclusion, IOL water content may be linked to PCA reclosure, and the time to recurrence is shorter with each successive reclosure. Further research is needed to verify these findings and uncover additional contributing factors.

Findings in pseudophakic eye that developed liquefied aftercataract-like substance one day after vitrectomy.

Purpose: To report our findings in a case that had an accumulation of a translucent fluid between the intraocular lens (IOL) and posterior lens capsule one day after vitrectomy for a vitreous hemorrhage. Observations: A 67-year-old woman was diagnosed with diabetes 20 years before the vitrectomy and was treated with panretinal photocoagulation (PRP) for proliferative diabetic retinopathy (PDR) 14 years earlier. She underwent cataract surgery with an implantation of an IOL 4 years earlier. She was referred to our hospital because of a vitreous hemorrhage, and we performed uneventful vitrectomy. However, the day after the operation, a translucent liquid substance that resembled liquefied aftercataract was observed in the lens capsule bag. With time, the liquid substance became cloudy. The opacification progressed for two years after the vitrectomy, and her visual acuity decreased. We then performed neodymium: YAG (Nd: YAG) laser posterior capsulotomy, and the cloudy liquid dispersed into the vitreous and the visual acuity improved. Conclusions and importance: Our findings indicate that liquified aftercataract-like substance can form after vitrectomy in a pseudophakic eye. We suggest that the aqueous humor might flow into the space behind the IOL during or just after the vitrectomy and was trapped behind the IOL optics. Then, the proliferating lens epithelial cells might be dissolved forming the white liquid substance immediately after the surgery.

Association between participation in hospital-led community activities and sense of security in continued community living among older adults in a rural district of Japan: A cross-sectional study.

For older adults to continue living in a community, they need to have a certain sense of security, especially in terms of the availability of healthcare in the community. The aim of this cross-sectional study was to explore important factors of the sense of security among older adults in their continued community living, with particular attention to hospital-led community activities. The participants comprised 252 randomly sampled older adults aged 65 years or older, living in a local community in western Japan, and ranging from being independent to physically and cognitively frail. Participants' sense of security in continued community living was assessed using a modified scale from past research on cancer care. Activities provided by local community organisations and hospitals were examined. The participants' mean age was 75.0 years, 144 (57.8%) were female and 32 (13.3%) were frail. Hospital-led groups (e.g. health lectures) and individual (e.g. health counselling) activities were used by 73 (30.5%) and 76 (31.9%) participants respectively. Among participants, 174 (73.4%) had participated in activities run by the local community, such as senior day celebrations or senior centre activities. A stronger sense of security was associated with participation in hospital-led individual activities (ß = 0.171, p = .036), being a member of a neighbourhood association (ß = 0.156, p = .020), frequency of contact with family members (ß = 0.145, p = .034) and lower depression (ß = -0.269, p < .001). Participation in community hospital-led individual activities may provide older adults opportunities to discuss their health-related concerns in a community setting, and thus might enhance their sense of security. In the aged society, the role of healthcare facilities may need to be expanded to facilitate outreach for older adults in the community to enhance their sense of security and actualise ageing in place.

Temporal Validation of an Assessment Tool that Predicts a Possibility of Home Discharge for Patients with Acute Stroke.

OBJECTIVES: Several prediction models have been developed to assess discharge destinations for patients with acute stroke; however, few studies have performed external validation. We aimed to perform a temporal external validation of a prediction tool to identify stroke patients with a high possibility of discharge to home. MATERIALS AND METHODS: From December 2017 to July 2019, consecutive patients with acute stroke were included. Clinical nurses and physical therapists applied the prediction model to assess the patients' possibility of home discharge. Whether or not the patient was discharged their own home was the outcome measured. We calculated the sensitivity and specificity of the model and evaluated the discrimination and calibration based on the area under the curve (AUC) and the calibration plot. RESULTS: Of the 1214 patients assessed, 618 (51%) were discharged home. Using the same cutoff values recommended in the study that first described the tool, we determined the sensitivity and specificity of 91% and 59%, respectively. The AUC to assess the model discrimination was 0.80 (95% confidence interval, 0.77-0.82) and the calibration plot showed acceptable agreement between the predicted and observed outcomes. CONCLUSIONS: The tool showed a high sensitivity, as expected, in the present study, which examined external validity during the different study periods.

Different pharmacoresistance of focal epileptic spasms, generalized epileptic spasms, and generalized epileptic spasms combined with focal seizures.

OBJECTIVE: Among standard treatments for infantile spasms, adrenocorticotropic hormone (ACTH) is reported as the best treatment, but ACTH is ineffective in one-half of the patients. To establish precision medicine, we examined pharmacoresistance of focal epileptic spasms (ES), generalized ES, and generalized ES combined with focal seizures, diagnosed based on the revised seizure classification of ILAE in 2017. METHODS: We conducted a retrospective nationwide study in Japan on the long-term seizure outcome of ES. Long-term seizure outcome was evaluated by seizure-free rate, seizure-free period, and Kaplan-Meier curve. Seizure-free was defined as seizure control for longer than 2 months. RESULTS: From the medical history of 501 patients, 325 patients had generalized ES only (GES group) at the start of the first treatment, 125 patients had generalized ES after focal seizure onset (FS-GES group), seven patients had focal ES after focal seizure onset (FS-FES group), and 24 patients had generalized ES combined with focal seizures after focal seizure onset (FS-GES + FS group). Seizure-free period of ES (generalized ES and focal ES) [mean (95% confidence interval)] was 2.7 (0.0-5.4) months in GES group, 1.1 (0.1-2.2) months in FS-GES group, 1.0 (0.2-1.9) months in FS-GES + FS group, and 0.1 (-0.2-0.5) months in FS-FES group. Seizure-free rate, seizure-free period, and Kaplan-Meier curve of generalized ES were almost the same in GES group and FS-GES group, with characteristics of superior response to ACTH. Mean seizure-free period of generalized ES combined with focal seizures was significantly shorter in FS-GES + FS group than in GES group. Mean seizure-free period of focal ES in FS-FES group was extremely short with exceedingly early relapse. SIGNIFICANCE: Pharmacoresistance was different in generalized ES, focal ES, and generalized ES combined with focal seizures. ES with focal features or with focal seizures may have focal lesions, thus consider surgical options earlier in the course.

Novel MSX1 frameshift mutation in a Japanese family with nonsyndromic oligodontia.

Congenital tooth agenesis is a common anomaly in humans. We investigated the etiology of human tooth agenesis by exome analysis in Japanese patients, and found a previously undescribed heterozygous deletion (NM_002448.3(MSX1_v001):c.433_449del) in the first exon of the MSX1 gene. The deletion leads to a frameshift and generates a premature termination codon. The truncated form of MSX1, namely, p.(Trp145Leufs*24) lacks the homeodomain, which is crucial for transcription factor function.

A novel LRP6 variant in a Japanese family with oligodontia.

Congenital tooth agenesis is a common anomaly in human development. We performed exome sequence analysis of genomic DNA collected from Japanese patients with tooth agenesis and their relatives. We found a novel single-nucleotide insertion in the LRP6 gene, the product of which is involved in Wnt/ß-catenin signaling as a coreceptor for Wnt ligands. The single-nucleotide insertion results in a premature stop codon in the extracellular region of the encoded protein.

Detection of bacteria in blood circulation in patients receiving cancer chemotherapy.

INTRODUCTION: Bacterial translocation, in which intestinal bacteria pass through the intestinal wall, enter the blood circulation, and spread to other sites of the body, is thought to cause bacteremia and sometimes febrile neutropenia (FN) in patients who receive cancer chemotherapy. MATERIALS AND METHODS: We collected blood samples from 39 patients with various cancers at baseline and after chemotherapy began (during chemotherapy) and explored how frequently bacteria could be detected in the blood using a highly-sensitive, bacterial rRNA-targeted reverse transcription quantitative polymerase chain reaction (PCR) assay. RESULTS: Bacterial traces, typically Escherichia coli and Enterobacter spp., were detected in 10 patients (25.6%) at baseline and 11 patients (28.2%) during chemotherapy. The bacterial traces were positive either at baseline or during chemotherapy in 3 (60%) of 5 patients who had FN, and 6 (46%) of 13 patients aged 65 years or older. CONCLUSION: These findings support the notion that bacterial translocation occurs in patients with cancer regardless of whether they receive chemotherapy and can lead to the development of FN and other treatment-related infections.

Evidence-based clinical practice guideline for adult Still's disease.

OBJECTIVES: Using an expert- and data-driven methodology, we have constructed the first clinical practice guidelines (CPGs) for adult Still's disease (ASD) after complete systematic review (SR) of the literature based upon the Medical Information Network Distribution Service (Minds) procedure. METHODS: The CPG committee for ASD organized by the Research Team for Autoimmune Diseases, the Research Program for Intractable Disease of the Japanese Ministry of Health, Labour, and Welfare has developed CPG for ASD 2017, according to the procedure proposed by Minds. The CPG development process includes (1) clarification of the purpose of CPG, (2) organization of the steering committee, (3) organization of the CPG committee and secretariat, (4) defining the scope (setting of clinical questions (CQs)), (5) SR, (6) development of recommendations, (7) drafting the CPG, (8) external evaluation and public comments, and (9) release. Because we wanted to construct CPG for ASD to encompass both adult-onset Still's disease (AOSD) and adult patients with systemic juvenile idiopathic arthritis (sJIA), we also included SR data from sJIA in this study. RESULTS: Twenty-six CQs were selected and roughly divided into the following items: (1) clinical findings (CQs 1-4), (2) laboratory findings (CQs 5-8), (3) complications (CQs 9-13), (4) treatment with oral medicine (CQs 14-19), (5) treatment with biological reagents (CQs 20-23), and (6) treatments for sJIA (CQs 25-26). Recommendations and the strength of the recommendations for these CQs were decided by a modified Delphi method. CONCLUSION: We have developed the first published CPG for ASD including AOSD and sJIA, which includes 26 CQs and recommendations. This guideline will help rheumatologists, non-specialized physicians, other healthcare providers, medical and health-related students, and patients and their family members to understand and treat ASD.

Feasibility of dose-dense epirubicin and cyclophosphamide with subcutaneous pegfilgrastim 3.6 mg support: a single-center prospective study in Japan.

BACKGROUND: Dose-dense chemotherapy consisting of a combination of epirubicin and cyclophosphamide (EC) improves the survival of patients with breast cancer. Although pegfilgrastim was used at a subcutaneous dose of 6.0 mg in a pivotal study of dose-dense EC treatment, pegfilgrastim at a dose of 3.6 mg has been approved in Japan. We have assessed the feasibility of dose-dense EC treatment supported with a 3.6 mg dose of pegfilgrastim by evaluating the relative dose intensity (RDI) and safety of the treatment, together with measuring the pegfilgrastim concentrations remaining on the day of starting the next cycle of chemotherapy. METHODS: Patients with primary breast cancer received a total of 4 cycles of dose-dense EC treatment every 2 weeks, together with a subcutaneous injection of 3.6 mg pegfilgrastim on the day after chemotherapy. The serum granulocyte colony-stimulating factor (G-CSF) concentrations were measured on the 15th day of every chemotherapy cycle. RESULTS: From March 2015 through to July 2016, a total of 51 patients (median age 51 years; range 33-73 years) were studied. The mean RDI was 95.2% (range 60.0-100%). Although most adverse events were consistent with those reported in previous studies, pneumocystis pneumonia developed in two patients during the following course of docetaxel treatment. The median serum G-CSF concentration was 92.5 (range 30.4-440) pg/ml. CONCLUSIONS: With support provided by pegfilgrastim injection at a dose of 3.6 mg, dose-dense EC is feasible and associated with maintenance of a high RDI. There was no clinically significant accumulation of serum G-CSF concentrations associated with the use of a 3.6 mg dose of pegfilgrastim at 2-week intervals.

Assessment Model to Identify Patients With Stroke With a High Possibility of Discharge to Home: A Retrospective Cohort Study.

BACKGROUND AND PURPOSE: Discharge planning for inpatients with acute stroke can enhance reasonable use of healthcare resources, as well as improve clinical outcomes and decrease financial burden of patients. Especially, prediction for discharge destination is crucial for discharge planning. This study aimed to develop an assessment model to identify patients with a high possibility of discharge to home after an acute stroke. METHODS: We reviewed the electronic medical records of 3200 patients with acute stroke who were admitted to a stroke center in Japan between January 1, 2011, and December 31, 2015. The outcome variable was the discharge destination of postacute stroke patients. The predictive variables were identified through logistic regression analysis. Data were divided into 2 data sets: the learning data set (n=2240) for developing the instrument and the test data set (n=960) for evaluating the predictive capability of the model. RESULTS: In all, 1548 (48%) patients were discharged to their homes. Multiple logistic regression analysis identified 5 predictive variables for discharge to home: living situation, type of stroke, functional independence measure motor score on admission, functional independence measure cognitive score on admission, and paresis. The assessment model showed a sensitivity of 85.0% and a specificity of 75.3% with an area under the curve equal to 0.88 (95% confidence interval, 0.86-0.89) when the cutoff point was 10. On evaluating the predictive capabilities, the model showed a sensitivity of 88.0% and a specificity of 68.7% with an area under the curve equal to 0.87 (95% confidence interval, 0.85-0.89). CONCLUSIONS: We have developed an assessment model for identifying patients with a high possibility of being discharged to their homes after an acute stroke. This model would be useful for health professionals to adequately plan patients' discharge soon after their admission.

Incidence of and risk factors associated with nedaplatin-related hypersensitivity reactions.

BACKGROUND: Nedaplatin (NDP)-related hypersensitivity reactions (HSRs) trigger adverse clinical events. Prediction and prevention of NDP-HSRs are thus essential to minimize the risk and maximize the benefit of NDP therapy. However, the incidence of NDP-HSRs and the associated risk factors remain unclear. METHODS: We retrospectively examined patients who received NDP monotherapy between April 2011 and July 2015 in Nagoya University Hospital. HSRs severity was defined according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE ver.4). Risk factors for NDP-HSRs were determined using multivariate logistic regression. RESULTS: Of 111 patients who received NDP monotherapy, 90 (81%) were female; median age was 59 years (range, 29-78 years). Eighty-eight patients had gynecological cancer and 20 suffered from head and neck cancer. Eight of 111 patients (7.2%) experienced NDP-HSRs, six of which developed in the second NDP cycle. However, all patients with NDP-HSRs were treated with carboplatin (CBDCA) for more than three cycles. Grade 3 and 4 HSRs developed in 2 patients. NDP-HSRs were significantly associated with a history of CBDCA-HSRs (odds ratio 37.5, 95% confidence interval 5.38-262, p < 0.001) and with the interval between NDP administration and the previous platinum treatment (odds ratio 13.9, 95% confidence interval 1.23-158, p = 0.034). CONCLUSION: The risk of NDP-HSRs increases in patients with a history of CBDCA-HSRs and in those administered NDP for more than 6 months after previous platinum treatment. Such individuals must be closely monitored if given NDP, even if they are expected to benefit from the treatment.

Intraarterial colforsin may improve the outcome of patients with aneurysmal subarachnoid hemorrhage: a retrospective study.

OBJECTIVE: Papaverine hydrochloride (PPV) has been widely used for pharmacologic angioplasty to dilate spastic vessels after aneurysmal subarachnoid hemorrhage (SAH). Colforsin daropate hydrochloride (CDH) has also recently been reported to be useful for reversal of cerebral vasospasm (CV). In this study, we compared the impacts of intraarterial PPV and CDH on the outcomes of SAH patients. METHODS: A consecutive series of SAH patients were retrospectively analyzed. Ninety-eight and 133 patients were included in the study during 1998-1999 (group A) and 2003-2005 (group B), respectively. PPV or CDH was the only agent used for pharmacologic angioplasty in groups A and B, respectively. Good outcome was defined as a modified Rankin scale score ≤ 2 at discharge. RESULTS: The percentages of patients without CV who had good outcomes were similar in groups A (78%) and B (81%, P = 0.91). However, the percentage of patients with CV with a good outcome was significantly higher in group B (66%) than in group A (34%, P = 0.032). Logistic regression revealed that age ≤ 65 years (P = 0.0001), World Federation of Neurological Surgeons (WFNS) grade ≤ 2 (P < 0.0001), CV (P = 0.0001), and group B (P = 0.0069) were independent causative factors for good outcome in the overall patient population. Age ≤ 65 (P = 0.0002) and WFNS grade ≤ 2 (P < 0.0001) were independent causative factors for good outcome in patients without CV, whereas only group B (P = 0.0089) was an independent factor for good outcome in patients with CV. CONCLUSION: CDH appears to be associated with a better outcome in patients with SAH.

[A case of myeloid sarcoma in the anterior mediastinum].

We report a case of myeloid sarcoma in the anterior mediastinum. The patient was a 33-year-old man with a chief complaint of right shoulder pain, right upper limb edema, and cough. Chest contrast-enhanced computed tomography (CT) revealed a partially enhanced anterior mediastinal tumor. A CT-guided biopsy was then performed, and a Hematoxylin-eosin (HE) stain revealed mitosis of tumor cells and other cells, including eosinophils. Immunohistochemical stains with myeloperoxidase, CD34, CD43, CD68 and c-Kit tests were positive for tumor cells. Due to a pathological diagnosis of myeloid sarcoma, he was treated with chemotherapy based on a diagnosis of acute myelogenous leukemia. After complete remission was obtained, the patient visited another hospital to receive an unrelated bone marrow transplantation. Although it rarely occurs as a mediastinal tumor, the prognosis of myeloid sarcoma is unfavorable, and thus should be taken into consideration as a differential diagnosis.

A case of ATLL (adult T-cell leukemia/lymphoma) mimicking odontogenic infection.

A case of adult T-cell leukemia/lymphoma (ATLL) in which cheek swelling was the initial symptom is presented. A 44-year-old man referred to our hospital with swelling in his right cheek, and a dental infection was suspected by a previous physician. Computerized tomographic scans and magnetic resonance imaging revealed tumorous lesions from the right alveolus of the maxilla to the anterior and posterior walls of the maxillary sinus. Anti-HTLV-1 antibodies were positive, and the level of sIL-2R was high; other laboratory test results were normal., based on immunohistochemical results on a specimen biopsy, the patient was diagnosed with a lymphoma-type ATLL. Immediately, the patient was treated in the department of hematologic medicine. After several courses of multiagent chemotherapy, 27 Gy radiation therapy was directed to the maxilla. However, remission was not achieved. Cord blood transplantation was subsequently performed, but his general condition gradually worsened until he died 7 months after his initial visit.

Bone formation in a rat calvarial defect model after transplanting autogenous bone marrow with beta-tricalcium phosphate.

In the present study, we evaluated the osteogenic potential of an autogenous bone marrow graft combined with beta-tricalcium phosphate (beta-TCP) in a rat calvarial bone defect model. The bone marrow harvested from the tibia of 7-week-old rats was grafted autogenously in a calvarial defect together with beta-TCP (=BTG group, n=16) or without beta-TCP (=BG group, n=16). Groups of animals were also treated with beta-TCP alone (=TG group, n=16) and control animals (n=8) received no graft implanted into the defect. We then observed the process of bone formation by histology, enzyme histochemistry and immunohistochemistry. Five days after grafting, in the BTG and BG groups, cell proliferation and osteogenic differentiation were observed. From 5 to 10 days after surgery, active Runx2, osteopontin (OPN), and TRAP- positive cells appeared in the BTG and BG groups. New bone formation started in the defect in both the BTG and BG groups. At 30 days after grafting, the BTG group showed new bone development and replacement of beta-TCP to fill the bone defect. New bone formation in the BTG group was significantly greater than in the BG group (P<0.01). The TG group showed no marked bone formation in the defect. The combination graft of bone marrow with beta-TCP showed marked bone formation in rat calvarial defects. Our results indicate that the combination grafts of bone marrow with beta-TCP may be an effective technique for repairing bone defects Beta-TCPgraft (TG) group.

[A case of rapidly progressing lung spindle cell carcinoma presenting as Pancoast syndrome].

We report a case of rapidly progressing spindle cell carcinoma presenting as Pancoast syndrome. The patient was a 59-year-old woman with a chief complaint of right forearm paresthesia. A chest computed tomography revealed a huge tumor in S1 and S2 in the right lung, invading the upper mediastinum and the first rib. A CT-guided lung biopsy was performed. H-E stain of the tissue revealed spindle-shaped tumor cells proliferating diffusely in a streaming pattern without definitive squamous or glandular differentiation. Immunohistochemical stains with CAM 5.2 and vimentin were positive for tumor cells. Based on a pathological diagnosis of spindle cell carcinoma (cT4N3M1, stage IV) she was treated with chemoradiotherapy. Despite treatment, the patient died 6 months after presenting.