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Background: Preoperative chemoradiotherapy (CRT) for patients with rectal cancer has not yet been established in Japan. We conducted a non-randomized phase II study to evaluate the efficacy and safety of preoperative CRT with S-1, a fixed-dose combination of tegafur, gimeracil, and oteracil potassium. Methods: We conducted a prospective, interventional, single-center study. Radiotherapy was administered at a total dose of 45 Gy (1.8 Gy in 25 fractions) for five weeks. S-1 was administered orally for a total of nine weeks (five weeks during and four weeks after radiotherapy) at a dose of 80 mg/m2/day. The endpoint was the pathological complete response (pCR) rate. The required sample size was calculated to be 30 individuals. The characteristics of the 28 patients included were as follows: cStage (II:12/ III:16), median age of 66 years (range 40–77 years), male/female (20/8), and lesion site (Ra-Rb:3/Rb:23/Rb-P:2). Results: Preoperative treatment was completed in 27 patients (96%). Treatment abandon was because of diarrhea. Grade 3 or higher adverse events were observed in only two patients (7%). Clinical downstaging was performed in eight patients (29%). Radical resection was achieved in 27 patients (96%), including 19 (68%) who underwent sphincter-preserving surgery. The pCR rate was 11% (three patients). The three-year disease-free survival rate was 79%, and the overall survival was 89%. No local recurrence occurred three years after surgery. Conclusions: Preoperative CRT with S-1 has an acceptable safety profile, and can potentially contribute to preserving anal function in patients with rectal cancer.Trial registration: UMIN Clinical Trial Registry: UMIN000013598. Registered 1 April 2014, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000015887

Objective The risk of embolization to distal territory or to new territory in mechanical thrombectomy remains a major issue despite advancements in technological device. This condition can be caused by a large and firm dropped thrombus without passing through a guiding catheter during stent retriever or aspiration catheter withdrawal. This report introduced a novel technique referred to as retrograde angiography to detect dropped thrombus. Methods The retrograde angiography to detect dropped thrombus technique is a kind of retrograde angiography that consists of a contrast medium injection via a distal microcatheter and aspiration through an inflated balloon-guiding catheter. This method was used to detect dropped thrombus at the balloon-guiding catheter tip when back flow was blocked from the balloon-guiding catheter after stent retriever or aspiration catheter withdrawal. We retrospectively reviewed four consecutive patients who underwent the retrograde angiography to detect dropped thrombus technique during mechanical thrombectomy for acute ischemic stroke due to large vessel occlusion in the anterior circulation between January 2018 and January 2021. Results Three of four patients had dropped thrombus, which was diagnosed with the technique and retrieved completely with subsequent procedures while maintaining the balloon-guiding catheter inflated. None of the patients experienced embolization to distal territory/embolization to new territory, and a successful reperfusion was achieved in all four cases. Conclusions The retrograde angiography to detect dropped thrombus is a technique to detect a dropped thrombus at the balloon-guiding catheter tip and allows us to retrieve it with subsequent mechanical thrombectomy procedures while maintaining the balloon-guiding catheter inflated and it may be useful for reducing the risk of embolization to distal territory/embolization to new territory.

Background The clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort. Aims To clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP. Methods We retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP. Results AIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI. Conclusions The clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.

A series of abdominal computed tomography scans of an asymptomatic 40-year-old woman with a history of umbilical cord blood transplantation (CBT) for leukemia at 19 years old revealed the long-term gradual development of a right hepatic vein thrombus and stenosis of the inferior vena cava, leading to a diagnosis of Budd-Chiari syndrome. The Budd-Chiari syndrome in this case might have been influenced by the patient's history of multiple liver abscesses after CBT and associated thrombus formation, in addition to the hormone replacement therapy with estradiol and dydrogesterone she was taking. This case provides insight into the development of Budd-Chiari syndrome.

Purpose: The purpose of this study was to investigate the relationships among plasma concentrations of lenvatinib, angiopoietin (Ang)-1 and Ang-2, and clinical responses to lenvatinib therapy in Japanese patients with thyroid cancer. Methods: Plasma concentrations of lenvatinib (C0) and Ang-1 and -2 were measured by HPLC and ELISA, respectively.Results: The median change rates of Ang-1 and Ang-2 at 1 month after treatment from baseline in 36 patients were -15.3% and -48.4%, respectively. However, the change of Ang-1 and Ang-2 at 1 month from baseline did not correlate with lenvatinib C0. In patients with partial response (PR) and stable disease to lenvatinib, Ang-2 at 1 month were significantly lower than Ang-2 at baseline (P < 0.001 and P < 0.05, respectively), but were not significantly lower in patients with progressive disease. The area under the ROC for PR prediction was 0.667, giving the best sensitivity (69.2%) and specificity (73.9%) at a threshold of the change rate of Ang-2 of -49.83%. A one year overall survival for patients having the change rate of Ang-2 of at least -49.83% and less than -49.83% were 62.5% and 40%, respectively. In patients who continued treatment with lenvatinib for 1 year, Ang-2 at 1 month and 1 year after treatment were significantly lower than those at baseline (each P < 0.001).Conclusion: The change of Ang-2 at 1 month after treatment from baseline rather than simply the Ang-2 level at baseline may be important as a biomarker of the inhibitory effect of angiogenesis by lenvatinib.

Purpose Anterior cruciate ligament (ACL) injury induces anterior and rotatory instability of the knee. However, the effect of this instability on the stress distribution in the knee joint in living participants is not clear. The aim of this study was to compare the distribution pattern of subchondral bone density across the proximal tibia in the knees with and without ACL injury, and to investigate the correlation between the distribution patterns of the subchondral bone density and the duration of ACL-deficiency. Methods Radiographic and computed tomography (CT) data pertaining to 20 patients with unilateral ACL injury without combined injury (ACL-deficient group) and 19 nontraumatic subjects (control group) were collected retrospectively. Subchondral bone density of the proximal tibia was assessed using CT-osteoabsorptiometry. Both the medial and lateral compartments of the proximal tibia were divided into three subregions of equal width in the sagittal direction. The percentage of high subchondral bone density areas (HDA%) in each subregion was quantitatively analyzed. Results HDA% of the posteromedial region was significantly higher in the ACL-deficient group (mean: 21.6%) than in the control group (14.7%) (p = 0.002). In contrast, HDA% of the anteromedial region was significantly lower in the ACL-deficient group (9.4%) than in the control group (15.3%) (p = 0.048). The logarithm of the time elapsed from ACL injury to CT examination showed a significant correlation with HDA% in the posteromedial region (p = 0.032). Conclusions Subchondral bone density in the posteromedial region significantly increased after ACL injury and correlated with the duration of ACL-deficiency in semi-log manner in meniscus intact knees. The increase in stress on the posteromedial region after ACL injury, which induces a change in the subchondral bone density, justifies early ACL reconstruction after ACL injury.

A 56-year-old postmenopausal woman with out-of-hospital cardiac arrest caused by acute myocardial infraction was successfully resuscitated by intensive treatments and recovered without any neurological disability. She was diagnosed as having familial hypercholesterolemia (FH) based on a markedly elevated low-density lipoprotein cholesterol (LDL-C) level and family history of premature coronary artery disease. Genetic testing in her family members showed that a variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene (c.2004C＞A, p.S668R), which had been previously reported as having uncertain significance, was associated with FH, indicating that the variant is a potential candidate for the FH phenotype. Next-generation sequencing analysis for the proband also showed that there was a heterozygous mutation of the ATP-binding cassette sub-family G member 5 (ABCG5) gene (c.1166G＞A, R389H), which has been reported to increase LDL-C level and the risk of cardiovascular disease. She was also diagnosed as having type 1 CD36 deficiency based on a lack of myocardial uptake of 123 I-labeled 15-(p-iodophenyl)-3-R,S-methyl-pentadecanoic acid in scintigraphy and the absence of CD36 antigen in both monocytes and platelets in flow cytometry. She had a homozygous mutation of the CD36 gene (c.1126-5_1127delTTTAGAT), which occurs in a canonical splice site (acceptor) and is predicted to disrupt or distort the normal gene product. To our knowledge, this is the first report of a heterozygous FH phenotype caused by possibly oligogenic variants of the PCSK9 and ABCG5 genes complicated with type I CD36 deficiency caused by a novel homozygous mutation. Both FH phenotype and CD36 deficiency might have caused extensive atherosclerosis, leading to acute myocardial infarction in the present case.

Recent studies have reported that confined high-intensity and diffuse low-intensity on sagittal T2-weighted magnetic resonance imaging (MRI) are distinctive features that are highly predictive of delayed union or nonunion on osteoporotic vertebral fracture (OVF). The objective of this study was to identify the characteristics of imaging findings predicting the risk for requiring surgical treatment in fresh OVF with poor prognostic features on MRI.We conducted a retrospective study of 74 patients (17 men and 57 women with a mean age of 81.1 years) of OVF with the poor prognostic MRI findings. We compared the imaging findings between the surgery group (16 patients) and the conservative group (58 patients): vertebral instability defined as the difference between the vertebral collapse ratio in dynamic X-rays, and the grade of posterior wall injury (Grade I, no spinal canal encroachment; Grade II,2 mm; Grade III, ≥2 mm) as well as the presence or absence of pedicle fracture (Grade I, none; Grade II, unilateral; Grade III, bilateral) on computed tomography.The mean vertebral instability was 24.0% ± 10.1% in the surgery group and 13.0% ± 7.8% in the conservative group, which was significantly different. Posterior wall injury in the surgery and conservative groups was Grade I in 0 and 29 cases, Grade II in 5 and 21 cases, and Grade III in 11 and 8 cases, respectively, constituting a significant difference. Pedicle fracture in the surgery and conservative groups was Grade I in 5 and 55 cases, Grade II in 6 and 2 cases, and Grade III in 5 and 1 case, respectively, also constituting a significant difference.The most high-risk OVF patients with poor prognostic MRI findings who required surgical treatment were those who exhibited greater vertebral instability as well as either more severe posterior wall injury or pedicle fracture.Retrospective clinical study.

Cervical ossification of the posterior longitudinal ligament (OPLL) is a contributing factor to spinal cord injury or trauma-induced myelopathy in the elderly. To reduce the incidence of these traumas, it is essential to diagnose OPLL at an early stage and to educate patients how to prevent falls. We thus evaluated the ability of our convolutional neural network (CNN) to differentially diagnose cervical spondylosis and cervical OPLL. We enrolled 250 patients with cervical spondylosis, 250 patients with cervical OPLL, and 180 radiographically normal controls. We evaluated the ability of our CNN model to distinguish cervical spondylosis, cervical OPLL, and controls, and the diagnostic accuracy was compared to that of 5 board-certified spine surgeons. The accuracy, average recall, precision, and F1 score of the CNN for classification of lateral cervical spine radiographs were 0.86, 0.86, 0.87, and 0.87, respectively. The accuracy was higher for CNN compared to any expert spine surgeon, and was statistically equal to 4 of the 5 experts and significantly higher than that of 1 expert. We demonstrated that the performance of the CNN was equal or superior to that of spine surgeons.

Background Vasodilator capacity of coronary circulation is an important diagnostic and prognostic tool in patients with coronary artery disease (CAD). We aimed to clarify the incidence of coronary microvascular dysfunction (CMD), defined as impaired modified coronary flow capacity (mCFC) proposed by Johnson and Gould and measured by 13N-ammonia myocardial perfusion positron emission tomography (PET), in patients without obstructive CAD and to evaluate the risk of future cardiovascular events. Methods This retrospective study recruited 407 consecutive CAD-suspected patients who underwent both pharmacological stress/rest 13N-ammonia PET and coronary angiography. Of the 407 patients, 137 patients (median age, 70 years; 63 women) were eligible and followed up (median, 19.8 months). Endpoints were defined as cardiovascular death or major adverse cardiovascular events (MACEs), such as cardiovascular death, nonfatal myocardial infarction, unplanned hospitalization for any cardiac reasons, and unplanned coronary revascularization. The impaired mCFC group included patients with mildly to severely reduced regional CFC in, at least, one vascular territory (n=34), while the remaining patients (n=103) were categorized as having preserved mCFC. Results Overall, cardiovascular death and MACEs occurred in five (4%) patients. The Kaplan–Meier curve showed a significant reduction in event-free survival for cardiovascular death (p=0.004) and MACEs (p Conclusions In CAD-suspected patients without obstructive coronary arteries, impaired mCFC was observed in approximately 25% and was associated with a higher risk of cardiovascular death and MACEs. The mCFC concept can help identify patients who would benefit from specific therapies or lifestyle modifications to prevent future MACEs and can clarify potential mechanisms of CMD.

Introduction:The purpose of this study was to investigate seasonal variation in stroke incidence using data from a large-scale stroke registry of general population in current Japan., Methods:Shiga Stroke Registry (SSR) is an ongoing population-based registry of stroke that occurred in the Shiga Prefecture in central Honshu, Japan. A total 6,688 cases of first-ever stroke, with onset dates ranging from 1 January 2011 to 31 December in 2013 were included in this study. Incidence rates of first-ever stroke in each season were estimated using the person-year approach and adjusted for age and sex using the Poisson regression models., Results:From 2011 to 2013, we identified a total of 6,688 stroke cases (3,570 men, 3,118 women), of which 4,480 cases had ischemic stroke (2,518 men, 1,962 women), 1,588 had intracerebral hemorrhage (857 men, 731 women) and 563 had subarachnoid hemorrhage (166 men, 397 women). Age- and sex-adjusted incidence rates of total stroke were 151 (95% confidence interval [CI] 144-160, p =, Conclusion:In the present large-scale stroke registry of general population, incidence rates of stroke were highest in winter and lowest in summer in current Japan.

Reproducibility is one of the most important issues for generalizing the results of clinical research; however, low reproducibility in neuroimaging studies is well known. To overcome this problem, the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) consortium, an international neuroimaging consortium, established standard protocols for imaging analysis and employs either meta‐ and mega‐analyses of psychiatric disorders with large sample sizes. The Cognitive Genetics Collaborative Research Organization (COCORO) in Japan promotes neurobiological studies in psychiatry and has successfully replicated and extended works of ENIGMA especially for neuroimaging studies. For example, (a) the ENIGMA consortium showed subcortical regional volume alterations in patients with schizophrenia (n = 2,028) compared to controls (n = 2,540) across 15 cohorts using meta‐analysis. COCORO replicated the volumetric changes in patients with schizophrenia (n = 884) compared to controls (n = 1,680) using the ENIGMA imaging analysis protocol and mega‐analysis. Furthermore, a schizophrenia‐specific leftward asymmetry for the pallidum volume was demonstrated; and (b) the ENIGMA consortium identified white matter microstructural alterations in patients with schizophrenia (n = 1,963) compared to controls (n = 2,359) across 29 cohorts. Using the ENIGMA protocol, a study from COCORO showed similar results in patients with schizophrenia (n = 696) compared to controls (n = 1,506) from 12 sites using mega‐analysis. Moreover, the COCORO study found that schizophrenia, bipolar disorder (n = 211) and autism spectrum disorder (n = 126), but not major depressive disorder (n = 398), share similar white matter microstructural alterations, compared to controls. Further replication and harmonization of the ENIGMA consortium and COCORO will contribute to the generalization of their research findings., The Cognitive Genetics Collaborative Research Organization (COCORO), which is a Japanese consortium established to elucidate psychiatric disorders and brain functions, replicated the results of the ENIGMA consortium, such as subcortical volume abnormalities and white matter microstructural abnormalities in schizophrenia, using the mega‐analysis method. These replication studies strengthened the reliability and generalization of the results of the ENIGMA consortium based on common and different methods in both consortiums. Further replication and harmonization of large consortia will contribute to the generalization of their research findings.

The aim of this study was to compare the quality of dynamic wave arc (DWA) and coplanar volumetric modulated arc therapy (co-VMAT) plans for the treatment of localized prostate cancer. The planning target volume (PTV)-rectum, a section of the PTV comprising the PTV minus that of the rectum, received 78 Gy in 39 fractions as the mean dose to the PTV-rectum. The DWA and co-VMAT plans were generated for each patient using the RayStation treatment planning system for the Vero4DRT system. The PTV-rectum dose (D95%: the percent dose irradiating 95% of the volume), homogeneity index (HI), conformity index (CI), as well as doses to the bladder wall, rectum wall (V10–70 Gy: the percent volume receiving 10–70 Gy), and bilateral femoral heads of the DWA and co-VMAT plans were compared. The output monitor unit (MU) and delivery time obtained for each set of plans were also investigated. In terms of target coverage, the DWA plans provided an average D95% of 75.5 Gy, which was comparable to the co-VMAT-plan D95% of 75.2 Gy (p

Extralobar pulmonary sequestration is generally located in the left thoracic cavity and is often identified prenatally or in infants. We experienced a rare case of multiple extralobar pulmonary sequestrations in the thoracic and abdominal cavities, incidentally detected in a 60-year-old woman by cancer screening. The patient underwent surgery by thoracoscopic and laparoscopic approaches simultaneously, and extralobar sequestration was histologically confirmed in each lesion. Preoperative diagnosis was difficult because of unusual multiple localization and an undetectable aberrant artery on imaging examinations.

What is known and objective We aim to add to the few reports on tacrolimus concentrations in breast milk and in maternal, umbilical vein and neonatal blood after maternal renal transplantation. Case summary In a 30-year-old pregnant woman, the tacrolimus concentration at delivery was the same in maternal, umbilical vein and neonatal blood. The breast milk/maternal blood tacrolimus ratio ranged from 0.40 to 0.64. What is new and conclusion The maternal and neonatal blood tacrolimus concentrations at birth are equivalent; thus, one must assume that maternal tacrolimus concentrations directly affect the foetus and/or neonate. Tacrolimus is not detectable in the neonate 3 weeks after birth, suggesting that there is minimal transfer through breast milk.

The aim was to identify the characteristics and treatment patterns of early and advanced stage endometrial cancer patients using real-world data.Patients' data extracted from a Japanese health insurance claims database were analyzed.Of the 12,449 endometrial cancer patients, 74.4% were in stage I, 5.1% in stage II, 12.0% in stage III, and 8.4% in stage IV. Their median age was 60.5 years, higher in advanced stages (III/IV) than in early stages (I/II). Overall, 11,055 patients (88.8%) underwent surgery, and 4977 patients (40.0%) received post-surgery treatment, including chemotherapy (4441: 35.7%), chemoradiation therapy (379: 3.0%), and radiation therapy (157 patients: 1.3%); 1394 patients (11.2%) were not treated by surgery, and 742 patients (6.0%) received other treatment, with chemotherapy (548: 4.4%), radiation therapy (105: 0.8%), and chemoradiation therapy (89: 0.7%). The rate of patients undergoing surgery decreased, and that receiving chemotherapy increased significantly as cancer stage progressed. Paclitaxel/carboplatin was the most frequent first-line regimen (85.4% of patients), whereas various combination and monotherapy regimens were used as second- and third-line regimens. The most frequent second-line monotherapy was paclitaxel. The rate of monotherapy increased as the treatment line progressed (first-line 3.5%, second-line 22.0%, and third-line 36.4%).The characteristics and treatment patterns of endometrial cancer patients differed between early and advanced stages, as did the chemotherapy regimens among first-, second-, and third-lines. Since various regimens were used for second- and third-line chemotherapies, development of appropriate second- and third-line chemotherapy regimens is warranted. A real-world analysis of cancer patients using a nationwide claims database may be a valuable approach to identifying unmet medical needs.

Bladder metastasis from lung adenocarcinoma is extremely rare. Unlike primary bladder urothelial tumors, the initial symptoms of this disease vary, and include pelvic pain, dysuria, and hematuria. There are few reports on cases without microscopic hematuria. An 86-year-old woman with a previous history of radiation therapy for lung adenocarcinoma complained of urinary frequency. A urinalysis was negative for hematuria and pyuria; thus, overactive bladder was suspected. However, the patient’s symptom worsened considerably, and cystoscopy revealed bladder tumor. Transurethral resection of the bladder tumor was performed. Based on the histological, immunohistochemical examination and clinical history, the final pathological diagnosis was bladder metastasis from lung adenocarcinoma. The patient died 19 days after the operation due to severe disease progression. In this rare case, a patient with bladder metastasis from lung adenocarcinoma did not show microscopic hematuria. Cystoscopy and computed tomography helped to make a rapid and accurate diagnosis.

BACKGROUND A strategy to predict mortality in elderly heart failure (HF) patients has not been established.Methods and Results:We retrospectively enrolled 413 HF patients aged ≥65 years (mean age 78 years) who had received comprehensive cardiac rehabilitation (CR) during hospitalization. Basic activities of daily life were assessed before discharge using the Barthel index (BI). Of 413 HF patients, 116 (28%) died during a median follow-up period of 1.90 years (interquartile range 1.20-3.23 years). An adjusted dose-dependent association analysis showed that the hazard ratio (HR) of mortality increased in an almost linear manner as the BI score decreased, and that a BI score of 85 corresponded to an HR of 1.0. Kaplan-Meier survival curves showed that the survival rate was lower for patients with a low BI (

Two patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency (ADA-SCID) received stem cell-based gene therapy (SCGT) using GCsapM-ADA retroviral vectors without preconditioning in 2003 and 2004. The first patient (Pt1) was treated at 4.7 years old, and the second patient (Pt2), who had previously received T cell gene therapy (TCGT), was treated at 13 years old. More than 10 years after SCGT, T cells showed a higher vector copy number (VCN) than other lineages. Moreover, the VCN increased with differentiation toward memory T and B cells. The distribution of vector-marked cells reflected variable levels of ADA requirements in hematopoietic subpopulations. Although neither patient developed leukemia, clonal expansion of SCGT-derived clones was observed in both patients. The use of retroviral vectors yielded clonal dominance of vector-marked clones, irrespective of the lack of leukemic changes. Vector integration sites common to all hematopoietic lineages suggested the engraftment of gene-marked progenitors in Pt1, who showed severe osteoblast (OB) insufficiency compared to Pt2, which might cause a reduction in the stem/progenitor cells in the bone marrow (BM). The impaired BM microenvironment due to metabolic abnormalities may create space for the engraftment of vector-marked cells in ADA-SCID, despite the lack of preconditioning., Graphical abstract, The distribution of vector-marked cells reflected variable levels of ADA requirements in hematopoietic subpopulations in ADA-SCID gene therapy. The use of retroviral vectors yielded clonal dominance of vector-marked clones, irrespective of the lack of leukemic changes.

Intravascular large B-cell lymphoma (IVLBCL) is a subtype of B-cell lymphoma, characterized by lymphoma cell proliferation within small blood vessels. We herein describe a rare case with long spinal cord lesions caused by venous congestive myelopathy associated with IVLBCL. An 81-year-old man presented with paraplegia of the lower limbs and sensory disturbances. Magnetic resonance imaging revealed intramedullary longitudinal T2-hyperintensity lesions in the thoracic cords. The patient died three months after disease onset, and a neuropathological analysis revealed predominantly atypical B-lymphocytes located sparsely in the veins of the spinal cord. IVLBCL should be considered in the differential diagnoses of long spinal cord lesions.

Objective Nonfasting serum triglyceride (TG) level is attracting more and more attention as an atherosclerosis-promoting factor. However, no study has investigated the relationships between nonfasting TG levels and carotid restenosis after carotid endarterectomy (CEA) or carotid artery stenting (CAS). This study was conducted to investigate if nonfasting TG levels can be used to assess a risk for carotid restenosis after CEA or CAS. Methods This was a single-center retrospective study. We reviewed 201 consecutive primary carotid artery revascularization procedures (39 CEAs and 162 CASs), which were performed from 2008 to 2018 for 179 patients (163 men and 16 women) with atherosclerotic carotid stenosis, and were followed up for at least 1 year. Clinical variables including nonfasting lipid profiles and findings of magnetic resonance plaque imaging were compared between groups with and without postprocedural carotid restenosis (≥50% stenosis on ultrasonography). Results During a mean follow-up period of 1413 days, 24 of 201 carotid stenosis procedures (11.9%) suffered restenosis after successful revascularization procedures. Multivariate analyses demonstrated that nonfasting TG level was the only independent risk factor of postprocedural restenosis. The receiver operating characteristic curve analyses revealed that a cutoff value of nonfasting TG to discriminate postprocedural carotid restenosis was 127.5 mg/dL, which was much lower than the upper limit of normal. Conclusions This study showed that nonfasting TG level may be a useful marker to predict carotid restenosis after CEA or CAS, and could be a new therapeutic target to prevent carotid restenosis after revascularization procedures.

We herein report a 70-year-old man diagnosed with IgG4-related hypertrophic pachymeningitis with skull base involvement, who presented with isolated glossopharyngeal and vagus nerve palsy. Contrast-enhanced magnetic resonance imaging (MRI) showed enhanced dural thickening of the posterior clivus and skull base involvement. When a patient with hypertrophic pachymeningitis presents with isolated cranial neuropathy without systemic manifestations or definite MRI abnormalities, it is difficult to make a diagnosis, and the patient may be misdiagnosed. This case suggests that a detailed radiological evaluation including contrast enhancement of the skull base is very important in patients with isolated glossopharyngeal and vagus nerve palsy.

Gestational diabetes mellitus (GDM) is known to be a significant risk factor for the future development of type 2 diabetes. Here, we investigated whether a precise evaluation of β- and α-cell functions helps to identify women at high risk of developing glucose intolerance after GDM. Fifty-six women with GDM underwent a 75-g oral glucose tolerance test (OGTT) at early (6-12 weeks) postpartum. We measured their concentrations of glucose, insulin, proinsulin and glucagon at fasting and 30, 60 and 120 min. At 1-year post-delivery, we classified the women into a normal glucose tolerance (NGT) group or an impaired glucose tolerance (IGT)/diabetes mellitus (DM) group. Forty-three of the 56 women completed the study. At 1-year post-delivery, 17 women had developed IGT/DM and 26 women showed NGT. In the early-postpartum OGTTs, the IGT/DM group showed a lower insulinogenic index, a less glucagon suppression evaluated by the change from fasting to 30 min (ΔGlucagon 30 min), and a higher glucagon-to-insulin ratio at 30 min compared to the NGT group. There were no significant between-group differences in proinsulin levels or proinsulin-to-insulin ratios. Insulinogenic index0.6 and ΔGlucagon 30 min0 pg/mL were identified as predictors for the development of IGT/DM after GDM, independent of age, body mass index, and lactation intensity. These results suggest that the bihormonal disorder of insulin and glucagon causes the postpartum development of glucose intolerance. The measurement of plasma insulin and glucagon during the initial OGTT at early postpartum period can help to make optimal decisions regarding the postpartum management of women with GDM.

Background/aim To evaluate the outcomes of induction chemotherapy and/or external beam radiotherapy (EBRT) followed by brachytherapy (BT) in patients with tongue cancer who had a waiting period for BT or a large tumor that was not suitable for BT. Patients and methods As an induction therapy, chemotherapy with tegafur/gimeracil/oteracil (S-1), EBRT or both S-1 chemotherapy and EBRT was prescribed. BT was performed using Au-198 grains or Ir-192 pins. Local control (LC), lymph node metastasis-free survival (LNMFS), overall survival (OS), and complication rates were calculated. Results Forty-nine patients were enrolled in this study. The 3-year LC, LNMFS, and OS rates for cT1-2 patients were 84%, 45%, and 69%, respectively. The 3-year LC, LNMFS, and OS rates for cT3 patients were 77%, 58%, and 79%, respectively. The incidence of Grade 3 or 4 complications was 6%. Conclusion Induction therapy contributed to the efficacy of the subsequent BT in LC rate.

Bone turnover markers (BTMs) are released during the bone remodelling cycle and are measurable in blood or urine, reflecting bone remodelling rate. They have been useful in elucidating the pharmacodynamics and effectiveness of osteoporosis medication in clinical trials and are increasingly used in routine clinical management of osteoporosis, especially for monitoring therapy, in addition to their use in other metabolic bone disease such as Paget's disease of bone and osteomalacia. Serum β isomerised C-terminal telopeptide of type I collagen and pro-collagen I N-terminal propeptide have been designated as reference BTMs for use in osteoporosis. In addition, bone-specific isoenzyme of alkaline phosphatase (B-ALP) secreted by osteoblasts and tartrate-resistant acid phosphatase 5b (TRACP-5b) secreted by osteoclasts are also found to be specific markers of bone formation and resorption, respectively. The concentrations of the latter enzymes in blood measured by immunoassay provide reliable measures of bone turnover even in the presence of renal failure. B-ALP is recommended for use in the assessment of renal bone disease of chronic kidney disease, and TRACP-5b shows promise as a marker of bone resorption in that condition. BTMs in blood do not suffer from biological variation to the same extent as the older BTMs that were measured in urine. Appropriate patient preparation and sample handling are important in obtaining accurate measures of BTMs for clinical use. Reference change values and treatment targets have been determined for the reference BTMs for their use in monitoring osteoporosis treatment. Further ongoing studies will enhance their clinical applications.

Langerhans cell histiocytosis is a neoplastic condition of Langerhans cells, and can be associated with other neoplasms, especially BRAF-mutant hematological tumors and papillary thyroid carcinoma. Here, we present the first case of co-existing Langerhans cell histiocytosis and low cumulative sun damage (low-CSD) melanoma, both of which had a BRAF V600E mutation. A 49-year-old man had a 45 × 43 × 15 mm semi-pedunculated pigmented tumor in his back but had no other systemic symptoms. Histopathology revealed a 2 mm-sized incidental focus of Langerhans cell histiocytosis within a large lesion of low-CSD melanoma. Diffuse immunoexpression of CD1a, langerin/CD207, S100 protein, and BRAF (VE1) was observed in the focus of Langerhans cell histiocytosis. Sanger sequencing with microdissection confirmed BRAF V600E mutation in the component of Langerhans cell histiocytosis. Interestingly, the advanced melanoma also harbored the same BRAF V600E mutation, although the significance of this tumor combination is still unknown. This article is protected by copyright. All rights reserved.

Purpose. To determine the effects of cataract surgery on contrast visual acuity and retinal sensitivity in patients with retinitis pigmentosa. Methods. Retinal sensitivity and contrast visual acuity were determined by microperimetry (MAIA) and contrast sensitivity acuity tester (CAT-CP), respectively, before and after cataract surgery. The significance of the correlations between visual acuity, retinal sensitivity, contrast visual acuity, improvements after surgery, and macular structure before and after cataract surgery was determined. Results. Retinal sensitivity and contrast visual acuity were significantly improved after cataract surgery. The correlations among postoperative visual acuity, postoperative retinal sensitivities, and preoperative ellipsoid zone length were significant. The postoperative retinal sensitivity of the central 10° and the ellipsoid zone length was particularly significantly correlated. Preoperative contrast visual acuity and the amount of improvement and preoperative retinal sensitivity and the amount of improvement were significantly negatively correlated. The contrast visual acuity under both the 100% and 10% photopic and mesopic conditions improved significantly after cataract surgery. Conclusions. Cataract surgery in retinitis pigmentosa patients with preserved ellipsoid zones significantly improved retinal sensitivity and contrast visual acuity. Cataract surgery can be expected to improve retinal sensitivity and contrast visual acuity under various conditions, even if preoperative visual parameters are low, as long as the ellipsoid zone is preserved.

Background: Obesity is a critical cardiovascular risk factor that has been defined in terms of body mass index (BMI), abdominal circumference (AC), and fat area. In this study, we examined which markers of obesity are most closely associated with major adverse cardiovascular events (MACE). Methods and Results: This prospective cohort study enrolled 529 consecutive patients who initially underwent coronary computed tomography angiography for screening of coronary atherosclerosis at Fukuoka University Hospital (FU-CCTA Registry) and either were clinically suspected of having coronary artery disease (CAD) or had at least 1 cardiovascular risk factor with a follow-up of up to 5 years. Measurements of subcutaneous fat area (SFA), visceral fat area (VFA), and AC were quantified using multidetector row computed tomography. The primary endpoint was MACE. SFA and the SFA to VFA ratio (SFA/VFA) were significantly lower in the MACE than non-MACE group. SFA, AC, BMI, and SFA/VFA were each independently associated with MACE. Receiver operating characteristic curve analysis revealed a greater area under the curve for SFA/VFA than for the other parameters. The cut-off level of SFA/VFA with the greatest sensitivity and specificity for the diagnosis of MACE was 1.45 (sensitivity 0.849, specificity 0.472). Conclusions: Our results suggest that SFA/VFA may be a marker for evaluating the presence of MACE.

Background: Many issues persist in the today’s Alzheimer’s disease (AD) screening and the breakthrough method is desired. Objective: We aim to validate the association between venous reflux and AD, and to develop a new method for AD screening. Methods: We examined spontaneous echo contrast, area, diameter, retrograde velocity, and anterograde velocity of the bilateral cervical internal jugular vein (IJV) using carotid ultrasonography. Results: A total of 112 patients participated in this study, with 26 diagnosed as AD. The proportion of both or either IJV spontaneous echo contrast (+) occupied 25 of total 26 AD patients, which showed 96.2%of sensitivity and 98.5%negative predictive value. The IJV velocities also showed significant correlation with AD diagnosis, although the IJV area or diameter did not. Conclusion: Our results indicate that the validation of the spontaneous echo contrast or velocities of the IJV are convenient AD diagnosis screening methods and that the venous reflux disturbance correlates with AD development.

Background and purpose Multiple embolic sources are sometimes observed simultaneously in patients with embolic stroke. The present study investigated the effects of coexisting aortic arch atheroma ≥ 4 mm thick and atrial fibrillation (AF) on short-term stroke recurrence and functional outcome. Methods Transesophageal echocardiography (TEE) was performed in consecutive embolic stroke patients, and 395 patients were classified into 4 groups according to the presence of aortic arch atheroma ≥ 4 mm thick and AF: AF - /ARCH - group, AF + /ARCH - group, AF - /ARCH + group, and AF + /ARCH + group. In accordance with these 4 groups, we evaluated stroke recurrence and all-cause death for 3 months after stroke onset, and also evaluated the 3-month functional outcome using the modified Rankin scale (mRS). Results Among the 128 AF patients, 39.1% also had aortic arch atheroma ≥ 4 mm thick. Of the 395 enrolled cases, the AF + /ARCH + group showed the highest frequencies of stroke recurrence and all-cause death during 3 months after onset. On multivariate analysis, stroke recurrence or all-cause death during 3 months after onset was relatively more frequent in the AF + /ARCH + group than in the AF + /ARCH - group (OR, 2.34; 95% CI, 0.82-6.69; p = 0.11), but that was not statistically significant, and poor functional outcome (mRS score 3-6) at 3 months was significantly more frequent in the AF + /ARCH + group than in the AF + /ARCH - group (OR, 2.59; 95% CI, 1.08-6.24; p = 0.0339). Conclusions Aortic arch atheroma concomitant with AF is not rare and appears associated with increased risks of stroke recurrence and poor functional outcome.

The accurate and early diagnosis and classification of cancer origin from either tissue or liquid biopsy is crucial for selecting the appropriate treatment and reducing cancer-related mortality. Here, we established the CAncer Cell-of-Origin (CACO) methylation panel using the methylation data of the 28 types of cancer in The Cancer Genome Atlas (7950 patients and 707 normal controls) as well as healthy whole blood samples (95 subjects). We showed that the CACO methylation panel had high diagnostic potential with high sensitivity and specificity in the discovery (maximum AUC = 0.998) and validation (maximum AUC = 1.000) cohorts. Moreover, we confirmed that the CACO methylation panel could identify the cancer cell type of origin using the methylation profile from liquid as well as tissue biopsy, including primary, metastatic, and multiregional cancer samples and cancer of unknown primary, independent of the methylation analysis platform and specimen preparation method. Together, the CACO methylation panel can be a powerful tool for the classification and diagnosis of cancer.

Considering the increasing number of identified driver oncogene alterations, additional genetic tests are required to determine the treatment for advanced non‐small‐cell lung cancer (NSCLC). Next‐generation sequencing can detect multiple driver oncogenes simultaneously, enabling the analysis of limited amounts of biopsied tissue samples. In this retrospective, multicenter study (UMIN ID000039523), we evaluated real‐world clinical data using the Oncomine Dx Target Test Multi‐CDx System (Oncomine DxTT) as a companion diagnostic system. Patients with NSCLC who were tested for a panel of 46 genes using the Oncomine DxTT between June 2019 and January 2020 were eligible for enrollment. Patients from 19 institutions affiliated to the West Japan Oncology Group were recruited. The primary endpoint of the study was the success rate of genetic alteration testing in four driver genes (EGFR, ALK, ROS1, and BRAF) using the Oncomine DxTT. In total, 533 patients were enrolled in the study. The success rate of genetic alteration testing for all four genes was 80.1% (95% CI 76.5%‐83.4%). Surgical resection was associated with the highest success rate (88.0%), which was significantly higher than that for bronchoscopic biopsy (76.8%, P = .005). Multivariate analysis revealed a significant difference for surgical resection alone (P = .006, 95% CI 1.36‐6.18, odds ratio 2.90). Although the success rate of genetic alteration testing immediately after Oncomine DxTT induction was not sufficient in this study, optimizing specimen quantity and quality may improve the use of driver gene testing in clinical settings., The mutation identification success rate for all four genes was 80.1%. Surgical resection was associated with the highest success rate. Multivariate analysis showed a significant difference for surgical resection alone.

Background Patients with very‐high‐risk prostate cancer (VHRPCa) have earlier biochemical recurrences (BCRs) and higher mortality rates. It remains unknown whether extended robot‐assisted laparoscopic prostatectomy (eRALP) without neoadjuvant or adjuvant therapy can improve the outcomes of VHRPCa patients. We aimed to determine the feasibility and efficacy of eRALP as a form of monotherapy for VHRPCa. Methods Data from 76 men who were treated with eRALP without neoadjuvant/adjuvant therapy were analyzed. eRALP was performed using an extrafascial approach. Extended pelvic lymph node (LN) dissection (ePLND) included nodes above the external iliac axis, in the obturator fossa, and around the internal iliac artery up to the ureter. The outcome measures were BCR, treatment failure (defined as when the prostate‐specific antigen level did not decrease to, Extended robot‐assisted laparoscopic prostatectomy and extended pelvic lymph node dissection without adjuvant therapy is safe and effective for some patients with very‐high‐risk prostate cancer. The clinical stage and node positivity status predicted monotherapy failure, which may indicate good adjuvant therapy candidates.

Hyperthermia causes hyperventilation and concomitant hypocapnia and cerebral hypoperfusion. The cerebral hypoperfusion may underlie central fatigue. We demonstrate that sodium bicarbonate ingestion reduces heat-induced hyperventilation and attenuates hypocapnia-related cerebral hypoperfusion during prolonged exercise in the heat. In addition, we show that sodium bicarbonate ingestion reduces ratings of perceived exertion during the exercise. This study provides new insight into the development of an effective strategy for preventing central fatigue during exercise in the heat.

Objectives The aim of this AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial subgroup analysis was to examine rivaroxaban monotherapy benefits and their relation to the time between stenting and enrollment among patients after coronary stenting. Background Of 2,215 patients with atrial fibrillation and stable coronary artery disease in the AFIRE trial, rivaroxaban monotherapy was noninferior to rivaroxaban plus antiplatelet therapy (combination therapy) in terms of efficacy and superior for safety endpoints. However, thrombotic risk after antiplatelet therapy cessation remained a concern among 1,444 patients who had undergone coronary stenting >1 year before enrollment. Methods The benefits of rivaroxaban monotherapy in coronary stenting subgroups were assessed for efficacy (a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death of any cause), safety (major bleeding defined according to International Society on Thrombosis and Haemostasis criteria), ischemic endpoints, net adverse clinical event, and time between stenting and enrollment. Results Efficacy and safety endpoints for monotherapy were superior to combination therapy, with HRs of 0.70 for efficacy (95% CI: 0.50-0.98; P = 0.036) and 0.55 for safety (95% CI: 0.33-0.92; P = 0.019). For ischemic endpoints, the HR was 0.82 (95% CI: 0.58-1.15; P = 0.240). The HR became smaller with longer time between stenting and enrollment (efficacy, P for interaction = 0.158; safety, P = 0.097). Conclusions In patients with atrial fibrillation after coronary stenting, the benefits of rivaroxaban monotherapy for efficacy and safety endpoints were consistent with those in the whole AFIRE trial population. The benefits became apparent with longer time between stenting and enrollment. (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease Study [AFIRE]; UMIN000016612 , NCT02642419 )

A 43-year-old Japanese male, who had undergone open liver surgery for tumor resection, presented with decreased hemoglobin levels on Day 13 post-emergency-release transfusion of 16 units of Fy(a +) red blood cells. As the anemia was accompanied by increased lactate dehydrogenase, indirect bilirubin, and reticulocytes, as well as decreased haptoglobin, it was attributed to hemolysis. In the diagnostic workup for hemolytic reaction, the direct antiglobulin test result for IgG was positive and the antibody dissociated from the patient's peripheral red blood cells was identified as anti-Fya (titer, 4). The hemolytic reaction was transient (approximately 10 days), of moderate severity, and did not result in any obvious organ damage. However, a single compatible red blood cell transfusion of 2 units was required on Day 17 after the causative transfusion. Notably, HLA typing revealed that the patient carried the HLA-DRB1*04:03 allele, which has been implicated in immunogenicity and induction of anti-Fya response in Caucasian populations. In summary, this is the first documented case of definitive anti-Fya-mediated delayed hemolytic transfusion reaction associated with HLA-DRB1*04:03 in the Japanese population.

Background Although high volume centers (HVC) equate to improved outcomes in rectal cancer, the impact of surgical volume related to race is less defined. Methods Patients who underwent surgical resection for stage I-III rectal adenocarcinoma were divided into cohorts based on race and hospital surgical volume. Outcomes were analyzed following 1:1 propensity-score matching using logistic, Poisson, and Cox regression analyses with marginal effects. Results Fifty-four thousand one hundred and eighty-four (91.5%) non-Black and 5043 (8.5%) Black patients underwent resection of rectal cancer. Following 1:1 matching of non-Black (N = 5026) and Black patients, 5-year overall survival (OS) of Black patients was worse (72% vs. 74.4%, average marginal effects [AME] 0.66, p = 0.04) than non-Black patients. When compared to non-Black patients managed at HVCs, Black patients had worse OS (70.1% vs. 74.7%, AME 1.55, p = 0.03), but this difference was not significant when comparing OS between non-Black and Black patients managed at HVCs (72.3% vs. 74.7%, AME 0.62, p = 0.06). Length of stay was longer among Black and HVC patients across all cohorts. There was no difference across cohorts in 90-day mortality. Conclusions Although racial disparities exist in rectal cancer, this disparity appears to be ameliorated when patients are managed at HVCs.

To test discontinuation rates during Active Surveillance (AS) in patients diagnosed with incidental prostate cancers (IPCa) vs. tumors diagnosed at prostate biopsies (BxPCa). Retrospective single center analysis of 961 vs. 121 BxPCa vs. IPCa patients (2008–2020). Kaplan–Meier plots and multivariable Cox regression models tested four different outcomes: (1) any-cause discontinuation; (2) discontinuation due to ISUP GG upgrading; (3) biopsy discontinuation due to ISUP GG upgrading or > 3 positive cores; (4) biopsy discontinuation or suspicious extraprostatic extension at surveillance mpMRI. Then, multivariable logistic regression models tested rates of clinically significant PCa (csPCa) (ISUP GG ≥ 3 or pT ≥ 3a or pN1) after radical prostatectomy (RP). Median time follow-up was 35 (19–64) months. IPCa patients were at lower risk of any-cause (3-year survival: 79.3 vs. 66%; HR: 0.5, p = 0.001) and biopsy/MRI AS discontinuation (3-year survival: 82.3 vs. 72.7%; HR: 0.5, p = 0.001), compared to BxPCa patients. Conversely, IPCa patients exhibited same rates of biopsy discontinuation and ISUP GG upgrading over time, relative to BxPCa. In multivariable logistic regression models, IPCa patients were associated with higher rates of csPCa at RP (OR: 1.4, p = 0.03), relative to their BxPCa counterparts. AS represents a safe management strategy for IPCa. Compared to BxPCa, IPCa patients are less prone to experience any-cause and biopsy/MRI AS discontinuation. However, the two mentioned groups present similar rates of biopsy discontinuation and ISUP GG upgrading over time. In consequence, tailored AS protocols with scheduled repeated surveillance biopsies should be offered to all newly diagnosed IPCa patients.

Purpose To evaluate the outcomes of flanged intraocular lens fixation combined with microhook trabeculotomy. Patients and methods This study was a retrospective case series and included nine eyes of nine exfoliation glaucoma patients with subluxated lens or intraocular lens who underwent flanged intraocular lens fixation combined with microhook trabeculotomy between May 2019 and February 2020 at the Kochi University Hospital. The mean best-corrected visual acuity, intraocular pressure, and number of antiglaucoma medications were compared before and after surgery. Results The mean follow-up period was 5.67 ± 2.50 months. The mean best-corrected visual acuity improved significantly from 0.83 ± 0.72 preoperatively to 0.22 ± 0.34 at the last visit (p = 0.015). The mean intraocular pressure had significantly reduced from 27.1 ± 8.12 mmHg preoperatively to 13.2 ± 3.73 at the last visit (p = 0.008). The mean number of antiglaucoma medications decreased significantly from 4.56 ± 1.88 to 2.0 ± 1.0 at the last visit (p = 0.008). Postoperative intraocular pressure control to 21 mmHg or lower was achieved or maintained in all patients. Postoperative vitreous hemorrhage was observed in six eyes (66.7%), two of which needed reoperation. Conclusions This study showed that flanged intraocular lens fixation combined with microhook trabeculotomy might be effective for exfoliation glaucoma with subluxated lens or intraocular lens.

Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. Significance: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer. See related commentary by Letai, p. 290. This article is highlighted in the In This Issue feature, p. 275

Immune checkpoint inhibitors can often trigger immune‐related adverse events (irAEs), such as relapse of pre‐existing interstitial pneumonia. Here, we report the case of an 88‐year‐Japanese man diagnosed with advanced lung adenocarcinoma with a high tumor proportion score of programmed death‐ligand 1. Six years earlier, he had developed organizing pneumonia (OP), a subtype of interstitial pneumonia, that was treated with steroid pulse therapy maintained with prolonged prednisolone administration. We initiated pembrolizumab as the first‐line treatment. One month after the first pembrolizumab administration, high resolution computed tomography (HRCT) of the chest demonstrated ground‐glass opacities and consolidations. We suspected pembrolizumab‐induced OP relapse, an irAE. His oxygenation was normal; therefore, we discontinued pembrolizumab without additional treatment for OP relapse. Four months after OP relapse, HRCT showed no new findings. After significant amelioration of OP, although the size of the tumor shadow remained the same on HRCT, positron emission tomography‐computed tomography demonstrated the disappearance of the standardized uptake value of the primary tumor, mediastinal lymph nodes, and pleural nodules. In conclusion, this is the first report of a dramatic, significant metabolic response after a single pembrolizumab treatment despite the relapse of pre‐existing OP in a patient with advanced lung adenocarcinoma., High resolution computed tomography findings of the chest at (a) organizing pneumonia (OP) occurrence, (b) after OP amelioration, (c) diagnosis of lung cancer, (d) relapse of OP induced by pembrolizumab treatment, and (e) after amelioration of OP relapse.

Melanoma is the most aggressive type of skin cancer, and thus it is important to develop new drugs for its treatment. The present study aimed to examine the antitumor effects of solamargine a major alkaloid heteroside present in Solanum lycocarpum fruit. In addition solamargine was incorporated into nanoparticles (NP) of yttrium vanadate functionalized with 3-chloropropyltrimethoxysilane (YVO4:Eu3+:CPTES:SM) to determine antitumor activity. The anti-melanoma assessment was performed using a syngeneic mouse melanoma model B16F10 cell line. In addition, systemic toxicity, nephrotoxic, and genotoxic parameters were assessed. Solamargine, at doses of 5 or 10 mg/kg/day administered subcutaneously to male C57BL/6 mice for 5 days, decreased tumor size and frequency of mitoses in tumor tissue, indicative of a decrease in cell proliferation. Treatments with YVO4:Eu3+:CPTES:SM significantly reduced the number of mitoses in tumor tissue, associated with no change in tumor size. There were no apparent signs of systemic toxicity, nephrotoxicity, and genotoxicity initiated by treatments either with solamargine alone or plant alkaloid incorporated into NP. The animals treated with YVO4:Eu3+:CPTES:SM exhibited significant increase in spleen weight accompanied by no apparent histological changes in all tissues examined. In addition, animals treated with solamargine (10 mg/kg/day) and YVO4:Eu3+:CPTES:SM demonstrated significant reduction in hepatic DNA damage which was induced by tumor growth. Therefore, data suggest that solamargine may be considered a promising candidate in cancer therapy with no apparent toxic effects.

Adequate lymphadenectomy with at least 16 nodes retrieved at the time of gastrectomy is a quality measure recommended to ensure adequate staging. The minimum nodal retrieval recommended after receipt of neoadjuvant chemotherapy (NACT) is less defined. Patients with clinical stages 1 to 3 gastric adenocarcinoma who received NACT and surgical resection were identified from the 2004–2015 National Cancer Database. The optimal nodal harvest number was calculated with Cox spline regression modeling. Cohorts with a nodal harvest higher or lower than this number were 1:1 propensity score-matched. Overall survival (OS) was analyzed using Kaplan-Meier survival estimates. Among 4337 patients receiving NACT, the optimal minimal nodal harvest at gastrectomy was 23 nodes. Compared with the patients who had fewer than 23 nodes retrieved, the patients with at least 23 nodes examined (n = 1073, 24.7%) were more likely to be female (26.1% vs 22%; p = 0.006) and non-white (29.3% vs 18.5%; p < 0.0001), to have a Charlson-Deyo score of 0 (71.5% vs 66.8%; p = 0.005), and to have undergone resection at an academic facility (67.9% vs 51.5%; p < 0.0001). The patients with at least 23 nodes examined had higher proportions of high-grade tumor (62% vs 57.4%; p = 0.030), pT3 or pT4 tumor (56.3% vs 48.7%; p < 0.0001), body tumor (21.3% vs 12.5%; p < 0.0001), or antrum/pylorus tumor (15.3% vs 11.4%; p < 0.0001). The patients with at least 23 nodes were more likely to have lymph node metastases identified (61% vs 51%; p < 0.0001). After matching, the patients with at least 23 nodes (n = 990) demonstrated an improved 5-year OS (57.9% vs 49%; p = 0.001). The extent of lymphadenectomy during gastrectomy for gastric adenocarcinoma should not be reduced after NACT because adequate lymph node retrieval remains important for prognostication.

Background In Japan, forgoing life-sustaining treatment to respect the will of patients at the terminal stage is not stipulated by law. According to the Guidelines for the Decision-Making Process in Terminal-Stage Healthcare published by the Ministry of Health, Labor and Welfare in 2007, the Japanese Society for Dialysis Therapy (JSDT) developed a proposal that was limited to patients at the terminal stage and did not explicitly cover patients with dementia. This proposal for the shared decision-making process regarding the initiation and continuation of maintenance hemodialysis was published in 2014. Methods and results In response to changes in social conditions, the JSDT revised the proposal in 2020 to provide guidance for the process by which the healthcare team can provide the best healthcare management and care with respect to the patient's will through advance care planning and shared decision making. For all patients with end-stage kidney disease, including those at the nonterminal stage and those with dementia, the decision-making process includes conservative kidney management. Conclusions The proposal is based on consensus rather than evidence-based clinical practice guidelines. The healthcare team is therefore not guaranteed to be legally exempt if the patient dies after the policies in the proposal are implemented and must respond appropriately at the discretion of each institution.

Background Osimertinib is effective in patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC) resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, its effectiveness and safety in patients with poor performance status (PS) are unknown. Methods Enrolled patients showed disease progression after treatment with gefitinib, erlotinib, or afatinib; T790M mutation; stage IIIB, IV, or recurrent disease; and PS of 2–4. Osimertinib was orally administered at a dose of 80 mg/day. The primary endpoint of this phase II study (registration, jRCTs061180018) was response rate and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety. Results Thirty-three patients were enrolled, of which 69.7% and 24.2% had PS of 2 and 3, respectively. One patient was excluded due to protocol violation; in the remaining 32 patients, the response rate was 53.1%; disease control rate was 75.0%; PFS was 5.1 months; and OS was 10.0 months. The most frequent adverse event of grade 3 or higher severity was lymphopenia (12.1%). Interstitial lung disease (ILD) was observed at all grades and at grades 3–5 in 15.2% (5/33) and 6.1% (2/33) of patients, respectively. Treatment-related death due to ILD occurred in one patient. Patients negative for activating EGFR mutations after osimertinib administration had longer median PFS than those positive for these mutations. Conclusion Osimertinib was sufficiently effective in EGFR-TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. Plasma EGFR mutation clearance after TKI treatment could predict the response to EGFR-TKIs.

High precision is optimal in prehospital diagnostic algorithms for strokes and large vessel occlusions. We hypothesized that prehospital diagnostic algorithms for strokes and their subcategories using machine learning could have high predictive value. Consecutive adult patients with suspected stroke as per emergency medical service personnel were enrolled in a prospective multicenter observational study in 12 hospitals in Japan. Five diagnostic algorithms using machine learning, including logistic regression, random forest, support vector machine, and eXtreme Gradient Boosting, were evaluated for stroke and subcategories including acute ischemic stroke with/without large vessel occlusions, intracranial hemorrhage, and subarachnoid hemorrhage. Of the 1446 patients in the analysis, 1156 (80%) were randomly included in the training (derivation) cohort and cohorts, and 290 (20%) were included in the test (validation) cohort. In the diagnostic algorithms for strokes using eXtreme Gradient Boosting had the highest diagnostic value (test data, area under the receiver operating curve 0.980). In the diagnostic algorithms for the subcategories using eXtreme Gradient Boosting had a high predictive value (test data, area under the receiver operating curve, acute ischemic stroke with/without large vessel occlusions 0.898/0.882, intracranial hemorrhage 0.866, subarachnoid hemorrhage 0.926). Prehospital diagnostic algorithms using machine learning had high predictive value for strokes and their subcategories.

The Epstein-Barr virus (EBV) infection status in patients with inflammatory bowel disease (IBD), particularly those using thiopurines, may be associated with the risk of lymphoproliferative disorder and hemophagocytic lymphohistiocytosis. This was the first multicenter survey of EBV infection in Japanese patients with IBD. Factors related to the EBV infection status were also investigated.Five tertiary institutions in Japan participated in this study to examine pediatric and adult patients with IBD. Serum EBV anti-viral capsid antigen (VCA) IgG, EBV anti-VCA IgM, and anti-EBV nuclear antigen-antibody were measured in 495 patients with IBD. The patients' information was obtained from their medical records. Prior EBV infection was defined as anti-VCA IgM negativity and anti-VCA IgG positivity (UMIN000033004).The patients' median age was 25 years (range 0-92 years). Of the 495 patients, nine were anti-VCA IgM-positive and 354 were anti-VCA IgG-positive (seroprevalence: 72.8%). The proportion of patients with prior EBV infection was 0% for those aged 5 years, 60% for those aged 30 years, and 90% for those aged 30 years. The proportion of EBV-uninfected patients using thiopurines was 28.4% (52/183) for all patients and 51.8% (44/85) for pediatric patients. Age was significantly associated with anti-VCA IgG seropositivity (p 0.01, odds ratio: 0.902, 95% confidence interval: 0.880-0.925). No cases of lymphoproliferative disorder, hemophagocytic lymphohistiocytosis, or chronic active EBV infection were reported.Approximately 30% of Japanese patients with IBD were EBV-uninfected, including those using thiopurines. Age was a significant factor for anti-VCA IgG seropositivity.

After a percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD), in-stent neoatherosclerosis may pose a risk of in-stent restenosis (ISR). To clarify whether non-fasting hypertriglyceridemia contributes to ISR, we examined the relationship between non-fasting hypertriglyceridemia (i.e., triglyceride (TG) level ≥ 200 mg/dL) and ISR after stenting with a bare metal stent (BMS) post-primary PCI in patients with CAD by means of a single-site retrospective analysis. A total of 1,039 patients with CAD were enrolled, and 86 patients (112 lesions) were evaluated for BMS-ISR 3-6 months post-primary PCI. The percentage of patients with non-fasting hypertriglyceridemia was significantly higher in the ISR (+) group than in the ISR (-) group (P < 0.009). The follow-up period and number of patients in the ISR (+) group were significantly smaller than those in the ISR (-) group (P < 0.001). There were no significant between-group differences in the other baseline patient characteristics before the primary PCI or at the time of the follow-up coronary angiography. However, at the follow-up period, the ISR (+) group had significantly lower diastolic blood pressure and high-density lipoprotein cholesterol levels (P = 0.015) and significantly higher TG levels (P = 0.012) than the ISR (-) group. A multiple logistic regression analysis demonstrated that non-fasting hypertriglyceridemia and a follow-up period of ≥ 6 months were independent risk factors for ISR after primary PCI in patients with BMS implantation for stenotic CAD (P = 0.006), with an adjusted odds ratio of 8.232 (1.201-56.410) and 0.006 (95% confidence interval < 0.001-0.045), respectively. Non-fasting hypertriglyceridemia may be an additional independent risk factor for BMS-ISR after primary PCI in patients with CAD.