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Aim High platelet reactivity (HPR) is associated with increased risks of thrombotic events in patients with coronary artery disease. The recently developed ABCD-GENE score identified five clinical and genetic factors (age, body mass index, chronic kidney disease, diabetes, and the CYP2C19 loss-of-function allele) for HPR, although the significance of various stages of each factor is unclear. Methods Four prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay with clopidogrel and prasugrel; genotyping of CYP2C19 was also performed. Each component of the ABCD-GENE score was divided into three subcategories. VerifyNow P2Y12 reactivity units ＞208 were defined as HPR. Results A total of 184 patients were included, of which 111 (60%) and 51 (28%) had HPR with clopidogrel and prasugrel. Chronic kidney disease had an impact on HPR on both clopidogrel and prasugrel, whereas the impact of diabetes was more evident in patients treated with prasugrel. Although the number of CYP2C19 loss-of-function alleles was clearly associated with a likelihood of HPR with clopidogrel, P2Y12 reactivity units with prasugrel treatment were also significantly and progressively higher in patients with more CYP2C19 loss-of-function alleles. Conclusions Clinical and genetic factors had a differential effect on a P2Y12 inhibitor reactivity with clopidogrel and prasugrel in patients with coronary artery disease. The severity of the factors also had a different impact on HPR.

Objectives The aim of the present study was to investigate the analgesic effects of repetitive transcranial magnetic stimulation over the primary motor cortex (M1-rTMS) using different stimulation parameters to explore the optimal stimulus condition for treating neuropathic pain. Materials and methods We conducted a randomized, blinded, crossover exploratory study. Four single sessions of M1-rTMS at different parameters were administered in random order. The tested stimulation conditions were as follows: 5-Hz with 500 pulses per session, 10-Hz with 500 pulses per session, 10-Hz with 2000 pulses per session, and sham stimulation. Analgesic effects were assessed by determining the visual analog scale (VAS) pain intensity score and Short-Form McGill Pain Questionnaire 2 (SF-MPQ2) score immediately before and immediately after intervention. Results We enrolled 22 adults (age: 59.8 ± 12.1 years) with intractable neuropathic pain. Linear-effects models showed significant effects of the stimulation condition on changes in VAS pain intensity (p = 0.03) and SF-MPQ2 (p = 0.01). Tukey multiple comparison tests revealed that 10-Hz rTMS with 2000 pulses provided better pain relief than sham stimulation, with greater decreases in VAS pain intensity (p = 0.03) and SF-MPQ2 (p = 0.02). Conclusions The results of this study suggest that high-dose stimulation (specifically, 10-Hz rTMS at 2000 pulses) is more effective than lower-dose stimulation for treating neuropathic pain.

BackgroundThe most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries.MethodsFace-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents.Results3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2–4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness.ConclusionADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.

Purpose Although intracranial dural arteriovenous fistula (DAVF) without retrograde leptomeningeal venous drainage (Borden type I) is reported to have a benign nature, no study has prospectively determined its clinical course. Here, we report a 3-year prospective observational study of Borden type I DAVF. Methods From April 2013 to March 2016, consecutive patients with DAVF were screened at 13 study institutions. We collected data on baseline characteristics, clinical symptoms, angiography, and neuroimaging. Patients with Borden type I DAVF received conservative care while palliative intervention was considered when the neurological symptoms were intolerable, and were followed at 6, 12, 24, and 36 months after inclusion. Results During the study period, 110 patients with intracranial DAVF were screened and 28 patients with Borden type I DAVF were prospectively followed. None of the patients had conversion to higher type of Borden classification or intracranial hemorrhage during follow-up. Five patients showed spontaneous improvement or disappearance of neurological symptoms (5/28, 17.9%), and 5 patients showed a spontaneous decrease or disappearance of shunt flow on imaging during follow-up (5/28, 17.9%). Stenosis or occlusion of the draining sinuses on initial angiography was significantly associated with shunt flow reduction during follow-up (80.0% vs 21.7%, p = 0.02). Conclusion In this 3-year prospective study, patients with Borden type I DAVF showed benign clinical course; none of these patients experienced conversion to higher type of Borden classification or intracranial hemorrhage. The restrictive changes of the draining sinuses at initial diagnosis might be an imaging biomarker for future shunt flow reduction.

OBJECTIVE There have been no accurate surveillance data regarding the incidence rate of spinal arteriovenous shunts (SAVSs). Here, the authors investigate the epidemiology and clinical characteristics of SAVSs. METHODS The authors conducted multicenter hospital-based surveillance as an inventory survey at 8 core hospitals in Okayama Prefecture between April 1, 2009, and March 31, 2019. Consecutive patients who lived in Okayama and were diagnosed with SAVSs on angiographic studies were enrolled. The clinical characteristics and the incidence rates of each form of SAVS and the differences between SAVSs at different spinal levels were analyzed. RESULTS The authors identified a total of 45 patients with SAVSs, including 2 cases of spinal arteriovenous malformation, 5 cases of perimedullary arteriovenous fistula (AVF), 31 cases of spinal dural AVF (SDAVF), and 7 cases of spinal epidural AVF (SEAVF). The crude incidence rate was 0.234 per 100,000 person-years for all SAVSs including those at the craniocervical junction (CCJ) level. The incidence rate of SDAVF and SEAVF combined increased with advancing age in men only. In a comparative analysis between upper and lower spinal SDAVF/SEAVF, hemorrhage occurred in 7/14 cases (50%) at the CCJ/cervical level and in 0/24 cases (0%) at the thoracolumbar level (p = 0.0003). Venous congestion appeared in 1/14 cases (7%) at the CCJ/cervical level and in 23/24 cases (96%) at the thoracolumbar level (p < 0.0001). CONCLUSIONS The authors reported detailed incidence rates of SAVSs in Japan. There were some differences in clinical characteristics of SAVSs in the upper spinal levels and those in the lower spinal levels.

Development of novel materials with desirable properties remains at the forefront of modern scientific research. Machine learning (ML), a branch of artificial intelligence, has recently emerged as a powerful technology in optoelectronic devices for the prediction of various properties and rational design of materials. Metal halide perovskites (MHPs) have been at the centre of attraction owing to their outstanding photophysical properties and rapid development in solar cell application. Therefore, the application of ML in the field of MHPs is also getting much attention to optimize the fabrication process and reduce the cost of processing. Here, we comprehensively reviewed different applications of ML in the designing of both MHP absorber layers as well as complete perovskite solar cells (PSCs). At the end, the challenges of ML along with the possible future direction of research are discussed. We believe that this review becomes an indispensable roadmap for optimizing materials composition and predicting design strategies in the field of perovskite technology in the future.

Summary IgG4-related hypophysitis is an autoimmune hypophysitis associated with IgG4-related disease. Swelling of the pituitary gland is responsive to steroid therapy, but the prognosis of pituitary function after the treatment remains unclear. The present case implies that transiently improved pituitary function can re-worsen during long-term follow-up in IgG4-related hypophysitis. A 71-year-old male patient with IgG4-related hypophysitis visited a nearby hospital with malaise, anorexia, and polyuria. Pituitary dysfunction was suspected, so he was referred to our hospital for further examination. Imaging studies and laboratory data showed swelling of the pituitary gland and panhypopituitarism, which dramatically improved following steroid therapy. There was no evidence of relapsing IgG4-related disease during prednisolone tapering. Pituitary function was examined after 4 years under treatment with low-dose prednisolone; surprisingly, anterior pituitary function had worsened again. Our case suggests a need for continuous monitoring of pituitary function after steroid therapy for IgG4-related hypophysitis. This report illustrates the natural course of pituitary function in IgG4-related hypophysitis and may be informative when considering the introduction of steroid therapy. Learning points Steroid therapy is an effective first-line therapy for pituitary dysfunction and pituitary swelling in IgG4-related hypophysitis. Pituitary function can worsen again during follow-up, despite transient improvement after steroid therapy in IgG4-related hypophysitis. Continuous monitoring of pituitary function is necessary for IgG4-related hypophysitis, regardless of disease activity.

Introduction Because of its lower risk of renal toxicity than vancomycin, teicoplanin is the preferred treatment for methicillin-resistant Staphylococcus aureus infection in patients undergoing continuous venovenous haemodiafiltration (CVVHDF) in whom renal function is expected to recover. The dosing regimen for achieving a trough concentration (Cmin) of ≥20 μg/mL remains unclear in patients on CVVHDF using the low flow rate adopted in Japan. Methods The study was conducted in patients undergoing CVVHDF with a flow rate of Results Overall, 60 patients were eligible for study inclusion. The proportion of patients achieving the Cmin target was significantly higher for the enhanced regimen than for the high-dose regimen (52.9% versus 8.3%, p = 0.003). In multivariate analysis, the enhanced regimen (odds ratio [OR] = 39.93, 95% confidence interval [CI] = 5.03–317.17) and hypoalbuminaemia (OR = 0.04, 95% CI = 0.01–0.44) were independent predictors of the achievement of Cmin ≥ 20 μg/mL. Conclusions An enhanced teicoplanin regimen was proposed to treat complicated or invasive infections by methicillin-resistant Staphylococcus aureus in patients receiving CVVHDF even with a low flow rate.

PURPOSE Tumor-intrinsic features may render large B-cell lymphoma (LBCL) insensitive to CD19-directed chimeric antigen receptor T cells (CAR-T). We hypothesized that TP53 genomic alterations are detrimental to response outcomes in LBCL treated with CD19-CAR-T. MATERIALS AND METHODS Patients with LBCL treated with CD19-CAR-T were included. Targeted next-generation sequencing was performed on pre–CAR-T tumor samples in a subset of patients. Response and survival rates by histologic, cytogenetic, and molecular features were assessed. Within a cohort of newly diagnosed LBCL with genomic and transcriptomic profiling, we studied interactions between cellular pathways and TP53 status. RESULTS We included 153 adults with relapsed or refractory LBCL treated with CD19-CAR-T (axicabtagene ciloleucel [50%], tisagenlecleucel [32%], and lisocabtagene maraleucel [18%]). Outcomes echoed pivotal trials: complete response (CR) rate 54%, median overall survival (OS) 21.1 months (95% CI, 14.8 to not reached), and progression-free survival 6 months (3.4 to 9.7). Histologic and cytogenetic LBCL features were not predictive of CR. In a subset of 82 patients with next-generation sequencing profiling, CR and OS rates were comparable with the unsequenced cohort. TP53 alterations (mutations and/or copy number alterations) were common (37%) and associated with inferior CR and OS rates in univariable and multivariable regression models; the 1-year OS in TP53-altered LBCL was 44% (95% CI, 29 to 67) versus 76% (65 to 89) in wild-type ( P = .012). Transcriptomic profiling from a separate cohort of patients with newly diagnosed lymphoma (n = 562) demonstrated that TP53 alterations are associated with dysregulation of pathways related to CAR-T-cell cytotoxicity, including interferon and death receptor signaling pathway and reduced CD8 T-cell tumor infiltration. CONCLUSION TP53 is a potent tumor-intrinsic biomarker that can inform risk stratification and clinical trial design in patients with LBCL treated with CD19-CAR-T. The role of TP53 should be further validated in independent cohorts.

Cancer is one of the major reasons for mortality across the globe. Many side-effects are associated with the formulations available in the market, affecting the quality of life of the patients. This has caused the researchers to find an alternative source of medications, such as herbal medicine, showing a promising effect in anticancer treatment; one such source is Pomegranate, which belongs to the family Punicaceae. Punica granatum contains many polyphenols that have antioxidant, antidiabetic, and therapeutic effects in the treatment and management of metabolic and cardiovascular diseases, as well as a favourable effect on anticancer therapy. Polyphenols like punicalin, punicalagin, and ellagic acid are a few of the many compounds responsible for the anticancer activity of pomegranate. Many preparations of pomegranate, such as Pomegranate Juice (PJ), Pomegranate seed oil (PSO), Pomegranate peel extract (PoPx), etc. are used in various clinical studies. These polyphenols show anticancer activity by either arresting the cell cycle in the G2/M phase, inducing apoptosis or damaging the DNA of tumor cells. This review explicitly discusses the role and mechanism of bioactives obtained from the pomegranate in the treatment and management of cancer. The chemical structure, properties, and role of pomegranate in the treatment of breast, lung, thyroid, colon, and prostate cancer have been focused on in detail. This review also discusses various targeted drug delivery approaches for tumour treatment as well as patented preparation of pomegranate compounds along with the ongoing clinical trials.

Covid-19 has become one of the most severe diseases causing the acute respiratory problems that has even killed millions of people worldwide. It was declared as the ongoing pandemic by the World Health Organization. It is an infectious virus which can be transmitted by sneezing, coughing and exhalation of air by any infected person. There are certain places where there are very high chances of rooms becoming contaminated like hospital rooms. In this context, we studied the transmission of covid-19 particles in an ICU room. In this paper, we have considered the combined effect of both of air-conditioning (AC) and a ceiling fan in the room. The infected person can transmit the disease when under influence of fan and AC, the work highlights the flow of aerosol particles considering the combined effect as well as the individual effects of fan and AC. The results also emphasized that the aerosol particles flow have a promising application in sanitizing the room.

Objectives To examine the longitudinal association between participation in social activities and healthy lifestyle behaviours. Study design This 2-year follow-up study used data from 6168 older adults (73.5 ± 5.3 years; 49% men). We studied participation in five types of social activities at baseline: participation in volunteer, sports, hobbies, senior clubs, and neighbourhood-association groups. Main outcome measures The healthy lifestyle behaviours were physical activity (time spent walking: ≥150 min/week; or less), eating habits (dietary variety score: ≥4 points; or less), and intellectual activity (subcomponents of the Tokyo Metropolitan Institute of Gerontology Index of Competence: 4 points; or less). Results In the follow-up survey, 19% of participants were physically inactive, 53% had unfavourable eating habits, and 34% had diminished intellectual activity. Multilevel modified Poisson regression analysis showed that participation in sports groups was associated with a lower relative risk (RR) of physical inactivity (RR=0.82 [0.72, 0.93]) and unfavourable eating habits (RR=0.95 [0.90, 1.00]). Participation in hobby groups reduced the RR of unfavourable eating habits (RR=0.93 [0.90, 0.97]) and diminished intellectual activity (RR=0.90 [0.85, 0.96]). Participation in volunteering was associated with a lower RR of diminished intellectual activity (RR=0.84 [0.75, 0.95]). Relative to non-participation, participating in two or more social activities was associated with a 9% (95% CI: 0.83, 1.00) lower RR for physical inactivity, a 12% (95% CI: 0.82, 0.95) lower RR for unfavourable eating habits, and a 17% (95% CI: 0.77, 0.89) lower RR for diminished intellectual activity. Conclusions Both the nature and the number of social activities determine the longitudinal effects of social participation on healthy lifestyle behaviours.

Background & Aims The obesity epidemic has increased the risk of non-alcoholic fatty liver disease (NAFLD) in both the general and chronic hepatitis B (CHB) populations. Our study aims to determine the prevalence of NAFLD in CHB patients based on controlled attenuation parameter (CAP), and the epidemiological, clinical and virological factors associated with severe hepatic steatosis. Methods The Canadian Hepatitis B Network cohort was utilized to provide a cross-sectional description of demographics, comorbidities, antiviral treatment, and HBV tests. Liver fibrosis and steatosis were measured by transient elastography (TE) and CAP, respectively. Any grade and severe steatosis were defined as CAP >248 and >280 dB/m, respectively. Advanced liver fibrosis was defined as TE measurement > 10.7kPa. Results In 1178 CHB patients (median age 47.4, 57.7% males, 75.7% Asian, 13% African, 6.5% White, 86% HBeAg negative, median HBV DNA of 2.44 log10IU/mL, 42.7% receiving treatment), the prevalence of any grade and severe steatosis was 53% and 36%, respectively. In the multivariate analysis, obesity was a significant predictor for severe steatosis (aOR 5.046, 95% CI: 1.22-20.93). Severe steatosis was a determinant associated with viral load (aOR 0.385, 95% CI: 0.20-0.75, p Conclusion In this large multi-ethnic CHB population, hepatic steatosis is common. Severe steatosis is independently associated with higher fibrosis, but negatively with HBV DNA, regardless of antiviral therapy history.

We report a case of endovascular aneurysm repair (EVAR) in a patient with horseshoe kidney (HSK) in whom preoperative contrast-enhanced (CE) computed tomography (CT) showed watershed sign. This sign enabled prediction of postoperative renal function by accurate renal volumetry. A 75-year-old man with HSK and a 59-mm abdominal aortic aneurysm was referred for treatment. Preoperative CECT showed watershed lines at the margin of the isthmus, which was perfused by the accessory renal arteries. Using this sign, we calculated the accurate volume of the isthmus, which was 24.5% of the total parenchyma. EVAR was safely performed without renal dysfunction.

Aims Cardiac ischaemia/reperfusion (I/R) injury remains a critical issue in the therapeutic management of ischaemic heart failure. Although mild hypothermia has a protective effect on cardiac I/R injury, more rapid and safe methods that can obtain similar results to hypothermia therapy are required. 2‐Methyl‐2‐thiazoline (2MT), an innate fear inducer, causes mild hypothermia resulting in resistance to critical hypoxia in cutaneous or cerebral I/R injury. The aim of this study is to demonstrate the protective effect of systemically administered 2MT on cardiac I/R injury and to elucidate the mechanism underlying this effect. Methods and results A single subcutaneous injection of 2MT (50 mg/kg) was given prior to reperfusion of the I/R injured 10 week‐old male mouse heart and its efficacy was evaluated 24 h after the ligation of the left anterior descending coronary artery. 2MT preserved left ventricular systolic function following I/R injury (ejection fraction, %: control 37.9 ± 6.7, 2MT 54.1 ± 6.4, P

Summary: Background & Aims: The prevalence of artificially administered nutrition and hydration (AANH) in different age groups among patients with advanced cancer remains unknown. The present study investigated the current utilization of AANH according to age groups in palliative care units. Methods: This was a secondary analysis of a prospective cohort study. We obtained information on primary nutritional administration routes during the first week of admission and data on the averaged calorie sufficiency rate or total calorie intake on the 7th day of admission. Patients were divided into five age groups (18–39, 40–59, 60–74, 75–89, and 90- years). Among patients receiving AANH, the proportions of higher-calorie AANH were compared between the five age groups. Results: A total of 1453 patients were included. The proportion of patients categorized as receiving nutrition and hydration via the parenteral route was the highest in the 18–39 and 40–59 groups (52.4 and 41.1%, respectively). Among patients receiving AANH (n = 534), the proportions of patients categorized into the

Background Successful restoration of epicardial coronary artery patency by primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) does not always lead to adequate reperfusion at the microvascular level. Aims This study sought to investigate the association between lipid-rich coronary plaque identified by near-infrared spectroscopy combined with intravascular ultrasound (NIRS-IVUS) and microvascular obstruction (MVO) detected by cardiac magnetic resonance imaging (MRI) after PPCI for STEMI. Methods We investigated 120 patients with STEMI undergoing PPCI. NIRS-IVUS was used to measure the maximum lipid-core burden index in 4 mm (maxLCBI4mm) in the infarct-related lesions before PPCI. Delayed contrast-enhanced cardiac MRI was performed to evaluate MVO 1 week after PPCI. Results MVO was identified in 40 (33%) patients. MaxLCBI4mm in the infarct-related lesion was significantly larger in the MVO group compared with the no-MVO group (median [interquartile range]: 745 [522-853] vs. 515 [349-698], pl0.001). Multivariable logistic regression model showed that maxLCBI4mm was an independent predictor of MVO (odds ratio: 24.7 [95% confidence interval: 2.5-248.0], p=0.006). Receiver-operating characteristic curve analysis demonstrated that maxLCBI4mm g600 was the optimal cut-off value to predict MVO (Youden index = 0.44 and area under the curve = 0.71) with a sensitivity of 75% and a specificity of 69%. Conclusions Lipid content measured by NIRS in the infarct-related lesions was associated with the occurrence of MVO after PPCI in STEMI.

The CHADS2 and CHA2DS2-VASc scores are widely used to assess ischemic risk in the patients with atrial fibrillation (AF). However, the discrimination performance of these scores is limited. Using the data from a community-based prospective cohort study, we sought to construct a machine learning-based prediction model for cerebral infarction in patients with AF, and to compare its performance with the existing scores. All consecutive patients with AF treated at 81 study institutions from March 2011 to May 2017 were enrolled (n = 4396). The whole dataset was divided into a derivation cohort (n = 1005) and validation cohort (n = 752) after excluding the patients with valvular AF and anticoagulation therapy. Using the derivation cohort dataset, a machine learning model based on gradient boosting tree algorithm (ML) was built to predict cerebral infarction. In the validation cohort, the receiver operating characteristic area under the curve of the ML model was higher than those of the existing models according to the Hanley and McNeil method: ML, 0.72 (95%CI, 0.66–0.79); CHADS2, 0.61 (95%CI, 0.53–0.69); CHA2DS2-VASc, 0.62 (95%CI, 0.54–0.70). As a conclusion, machine learning algorithm have the potential to perform better than the CHADS2 and CHA2DS2-VASc scores for predicting cerebral infarction in patients with non-valvular AF.

Objectives The aim of this study was to compare the incidence and prognostic significance of prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) according to racial groups. Background PPM after TAVR may be of more concern in Asian populations considering their relatively small annular and valve sizes compared with Western populations. Methods TP-TAVR (Transpacific TAVR Registry) was an international multicenter cohort study of patients with severe aortic stenosis who underwent TAVR in the United States and South Korea from January 2015 to November 2019. PPM was defined as moderate (0.65-0.85 cm2/m2) or severe ( Results Among 1,101 eligible patients (533 Asian and 569 non-Asian), the incidence of PPM was significantly lower in the Asian population (33.6%; moderate, 26.5%; severe, 7.1%) than in the non-Asian population (54.5%; moderate, 29.8%; severe, 24.7%). The 1-year rate of the primary outcome was similar between the PPM and non-PPM groups (27.5% vs 28.1%; P = 0.69); this pattern was consistent between Asian (25.4% vs 25.2%; P = 0.31) and non-Asian (28.7% vs 32.1%; P = 0.97) patients. After multivariable adjustment, the risk for the primary outcome did not significantly differ between the PPM and non-PPM groups in the overall population (HR: 0.95; 95% CI: 0.74-1.21), in Asian patients (HR: 1.07; 95% CI: 0.74-1.55), and in non-Asian patients (HR: 0.86; 95% CI: 0.63-1.19). Conclusions In this study of patients with severe aortic stenosis who underwent TAVR, the incidence of PPM was significantly lower in Asian patients than in non-Asian patients. The 1-year risk for the primary composite outcome was similar between the PPM and non-PPM groups regardless of racial group. (Transpacific TAVR Registry [TP-TAVR]; NCT03826264 )

With the Pfizer-BioNTech, Moderna, and now Johnson and Johnson COVID-19 vaccines readily available to the general population, the appearance of vaccine-induced axillary adenopathy on imaging has become more prevalent. We are presenting follow up to the first reported four cases of vaccine induced unilateral axillary adenopathy on imaging to our knowledge, which demonstrate expected self-resolving adenopathy. Our hope is that by providing this follow-up and reviewing current management guidelines, clinicians as well as patients will appreciate that this is an expected, benign, and self-resolving finding. In addition, we hope to quell any vaccine hesitancy brought about by recent mainstream media attention to this topic and ultimately empower patients to receive both the COVID-19 vaccine and undergo routine screening mammography, as both are vital to their health.

The perioperative management and technical details of laparoscopic clamp-crushing enucleation for low-malignant-potential pancreatic neuroendocrine neoplasms (PNENs) located close to the main pancreatic duct (MPD) in the body/tail of the pancreas using a perioperative MPD stent are reported. The procedure was performed in two patients with PNEN (13 and 10 mm in diameter) in the body/tail of the pancreas. A naso-pancreatic stent (NPS) was placed preoperatively in both patients. Resection was performed using Maryland-type bipolar forceps. The surgical duration was 139 and 55 min, and the estimated blood loss was 5 and 0 mL, respectively. One patient was discharged uneventfully on postoperative day (POD) 12. The other patient developed a grade B pancreatic fistula, but was discharged on POD 22. Laparoscopic clamp-crushing enucleation with an NPS might be a viable treatment option for tumors located close to the MPD.

BACKGROUND The Immunoscore is a useful prognostic and predictive factor for colorectal cancer. Frailty predicts overall and recurrence-free survival following resection of colorectal cancer, and the immunosuppressive state of frailty might affect tumor progression. This study investigated the relationship between the Immunoscore and frailty in colorectal cancer. METHODS This retrospective study included patients who underwent radical surgery for stage II and III colorectal cancer (n = 108). Patients were divided into frail (n = 11) and non-frail (n = 97) groups, and low (IS0-2) (n = 70) and high (IS3-4) Immunoscore groups (n = 38), for comparison. RESULTS American Society of Anesthesiologists physical status was higher, tumor diameter was larger, number of well-differentiated tumors was higher, albumin was lower, 5-year overall survival (OS) was lower (frail group: 50.0%, non-frail group: 90.5%, p

Background We sought to evaluate our distributed practice program developed for training for beating heart anastomosis by employing a novel beating heart simulator. Methods Eleven trainees watched and reviewed instructional video recordings of coronary anastomosis methods with a BEAT + YOUCAN training device, then performed coronary anastomosis procedures under a beating condition. Next, they participated in a four-hour training program developed by faculty surgeons. Ten different anastomosis components were assessed on a five-point rating scale (5, good; 3, average; 1, poor). After finishing the training program, each trainee again performed a coronary anastomosis procedure. Component scores were then compared before and after the training program. Results The mean time to completion of the procedure improved from 1033 ± 424 to 795 ± 201 s (p Conclusion Trainees who participated in our four-hour focused training program for coronary anastomosis with a novel beating heart simulator showed improved ability under the beating condition in regard to technical skills related to handling instruments.

Objective To investigate the association between oral health management (OHM) by dental hygienists and the occurrence of pneumonia, and determine the effectiveness of OHM in pneumonia prevention. Background In long-term care facilities in Japan, the need for professional OHM is increasing with an increase in the number of severely debilitated residents. Materials and methods A 1-year prospective multicentre cohort study was conducted using data from 504 residents (63 men; mean age: 87.4 ± 7.8 years) in Japanese long-term care facilities. Basic information, medical history, willingness to engage in oral hygiene behaviour, need for OHM and oral conditions were investigated at baseline. In addition, information on the occurrence of pneumonia was collected using a follow-up survey after one year. A Poisson regression analysis with robust standard errors was conducted, with pneumonia as the dependent variable, and factors associated with OHM and pneumonia occurrence as explanatory variables. Results Overall, 349 (69.2%) residents required OHM by dental hygienists during that year of follow-up. Of those, 238 (68.2%) were provided with OHM, and 18 (7.5%) developed pneumonia. Among the 111 patients (31.8%) who were not provided with OHM, 21 (18.9%) developed pneumonia. The OHM group had lower pneumonia rates than the non-OHM group (prevalence rate ratio: 0.388; 95% CI: 0.217-0.694). Conclusion Oral health management by dental hygienists was associated with a lower incidence of pneumonia among residents of long-term care facilities, underlining the importance of professional OHM for such individuals. It is recommended that OHM be practised routinely in long-term care facilities.

Background Digital mental health interventions are being used more than ever for the prevention and treatment of psychological problems. Optimizing the implementation aspects of digital mental health is essential to deliver the program to populations in need, but there is a lack of validated implementation outcome measures for digital mental health interventions. Objective The primary aim of this study is to develop implementation outcome scales of digital mental health for different levels of stakeholders involved in the implementation process: users, providers, and managers or policy makers. The secondary aim is to validate the developed scale for users. Methods We developed English and Japanese versions of the implementation outcome scales for digital mental health (iOSDMH) based on the literature review and panel discussions with experts in implementation research and web-based psychotherapy. The study developed acceptability, appropriateness, feasibility, satisfaction, and harm as the outcome measures for users, providers, and managers or policy makers. We conducted evidence-based interventions via the internet using UTSMeD, a website for mental health information (N=200). Exploratory factor analysis (EFA) was conducted to assess the structural validity of the iOSDMH for users. Satisfaction, which consisted of a single item, was not included in the EFA. Results The iOSDMH was developed for users, providers, and managers or policy makers. The iOSDMH contains 19 items for users, 11 items for providers, and 14 items for managers or policy makers. Cronbach α coefficients indicated intermediate internal consistency for acceptability (α=.665) but high consistency for appropriateness (α=.776), feasibility (α=.832), and harm (α=.777) of the iOSDMH for users. EFA revealed 3-factor structures, indicating acceptability and appropriateness as close concepts. Despite the similarity between these 2 concepts, we inferred that acceptability and appropriateness should be used as different factors, following previous studies. Conclusions We developed iOSDMH for users, providers, and managers. Psychometric assessment of the scales for users demonstrated acceptable reliability and validity. Evaluating the components of digital mental health implementation is a major step forward in implementation science.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) has received increased attention because of its novel treatment options. Carpal tunnel syndrome (CTS) is known as early symptoms in transthyretin amyloidosis (ATTR) preceding cardiac involvement and one of the “red flags” for ATTR-CM. A 64-year-old man underwent carpal tunnel release for carpal tunnel syndrome at 62 years. He was diagnosed with wild-type ATTR due to deposition of transthyretin (TTR) amyloid in flexor tenosynovium specimens and no TTR gene mutation. Examination for detection of cardiac involvement was performed after the operation, and there were no definitive findings of ATTR-CM; however, an early stage of ATTR-CM remained a possibility. Serial image evaluation and biomarker analysis revealed positive findings for ATTR-CM, and we performed an endomyocardial biopsy, resulting in the detection of amyloid deposition. He was diagnosed with ATTRwt-CM 2 years after the operation, and even then, he had no heart failure symptoms. Early diagnosis and treatment are important for the improvement of clinical outcomes in patients with ATTRwt-CM. TTR deposition in the ligaments or tendons is often observed in patients with CTS and should be considered at high risk of future ATTR-CM. Serial follow-up of these patients may enable the diagnosis of preclinical ATTR-CM.

Background In 2016, the Japanese government set the National Action Plan on antimicrobial resistance to reduce antibiotic prescriptions. However, the trends and variations of antibiotic prescription patterns in a routine healthcare setting during the fiscal year 2013–2018 across different clinics at a national level are unclear. Methods This retrospective cohort study included all clinics with >100 pediatric outpatients with infectious diseases per month during the fiscal year 2013–2018 using a national database in Japan. We investigated the trends in antibiotic prescription rates and their patterns and variations across different clinics over the six years following the 2019 World Health Organization Access, Watch, Reserve antibiotic groups, and Amoxicillin Index. Results A total of 2278 clinics with 94,414,170 infectious disease-related visits were eligible for the study. Most clinics showed higher Watch percentages (median 85.4%; IQR, 68.5–95.1) than Access percentages (median, 13.8%; IQR, 4.2–30.7) and Amoxicillin Index (median, 13.3%; IQR, 3.9–30.4). The introduction of the Action Plan changed annual absolute reductions in the antibiotic prescription rates from −16.0 DOTs/1000 visitors (95%CI, −16.4–15.6) to −239.3 per 1000 visitors (95%CI, −240.0–238.6). However, these impacts were heterogeneous across clinics. From 2013 to 2018, 41.4% reduced the antibiotic prescription rates by >33.3% (median, −1035.5 DOTs/1000 visitors; IQR, −1519.4–680.2), 18.7% did not change the rates (median, −40.3 DOTs/1000 visitors; IQR, −168.4–68.6), and 7.3% increased the rates by >10% (499.5 DOTs per 1000 visitors; IQR, 232.6–837.5). Conclusions We observed the National Action Plan's impacts and extensive prescription variations across different pediatric clinics. However, one-fourth of clinics did not improve antibiotic prescription patterns even after introducing the Action Plan.

This study aimed to compare the longitudinal change in depressive symptoms among healthcare professionals in Japan who are willing to receive novel coronavirus disease (COVID-19) vaccination and those who are unwilling to receive COVID-19 vaccination. The baseline survey was conducted in October 2020 (Survey time 1: T1); respondents in T1 were invited to participate in May 2021 (Survey time 2: T2). Depressive symptoms were assessed by the Patient Health Questionnaire-9 (PHQ-9). Group comparisons of the estimated mean of PHQ-9 score at T1 and T2 were estimated by the analysis of covariance. In T1, 597 participants (response rate: 4.4%) completed all questions. In T2, 211 participants (follow up rate: 35.3%) completed all questions. The group and time interaction effect was significant (F(1, 207)=3.9, p=0.049); depressive symptoms were worse among healthcare professionals who were unwilling to receive vaccination than among those who were willing to receive vaccination. This study showed that depressive symptoms were worse among healthcare professionals who were unwilling to receive COVID-19 vaccination than those who are willing to receive COVID-19 vaccination. This suggests that it is important to take care of healthcare professionals who are unwilling to receive vaccination to prevent mental health deterioration.

Purpose This study aimed to determine the association between home visits by a dentist and regular oral hygiene management by a dental hygienist (regular dental management: RDM) and weight loss among older adults in long-term care facilities. Methods A total of 468 older residents from 26 Japanese long-term care facilities participated in two surveys in 2018 and 2019. Participants were divided into two groups based on their diet during the baseline survey (regular diet, n = 256; dysphagia diet, n = 212). Participants with a regular diet were further divided into those who exhibited a weight loss >= 5% over 1 year (weight loss group: n = 77) and those with a weight loss < 5% (consistent weight group: n = 179). The explanatory variables were age, sex, baseline weight, Barthel index, and clinical dementia rating, as well as the patients' medical history of pneumonia, stroke, diabetes, and depression (which is reportedly associated with weight). Additionally, a Poisson regression with robust standard error, was carried out to analyze the explanatory variables, namely the prevalence of RDM noted during the study and functional teeth (which seemed to affect weight loss). Results A multivariate analysis revealed that older residents' lack of RDM, clinical dementia assessment, and their history of pneumonia (prevalence rate ratio: 0.35, 95% confidence interval 0.24-0.95) were all significantly associated with weight loss when on a regular diet. Conclusion Thus, weight loss and RDM were related to each other. Weight loss may be suppressed by incorporating RDMs during the early nursing care for older residents on regular diets. Key summary pointsAim This study aimed to clarify the relationship between weight loss and regular dental management among older adults in long-term care facilities through a 1-year, multicenter longitudinal study. Findings The absence of regular dental management among older residents in long-term care facilities (who follow regular diets) was associated with weight loss and malnourishment. Message Regular dental care procedures among older residents (who follow regular diets) in long-term care facilities may reduce weight loss and prevent malnutrition.

Background: An occupational disease is any disease developing primarily as a result of exposure to risk factors arising from work activity and contributing to a significant portion of work-related diseases. Although COVID-19 is not dermatotropic, prolonged contact with personal protective equipment—that is, goggles, face shields, N95 respirators, double-layered gloves, etc.—may cause various dermatoses. Several dermatoses due to PPE have been well documented, but facial dermatoses specifically due to the use of face masks remain a relatively uncharted entity. In this study, we report preliminary data on individuals experiencing various facial dermatoses due to the use of face masks. Objective: The aim was to study the various facial dermatoses associated with the use of a face mask. Materials and Methods: After obtaining informed consent, individuals using a face mask were enrolled in this single-institution, questionnaire-based, cross-sectional study. Results: A total of 364 participants were enrolled for the study, among which 59.3% revealed to have worn a face mask for more than six months. A majority used ear-looped N95 masks. Nine problem areas were identified in the study. Among the facial dermatoses observed, acne was the most frequently reported, followed by redness. Conclusion: In spite of contact dermatitis arising due to masks, it is recommended to use well-fitted and comfortable masks for sufficient periods of time to reduce the risk of transmission, ensure safety, and reduce mask-related side effects.

Background Dopamine neurotransmission plays a critical role in reward in drug abuse and drug addiction. However, the role of dopamine in the recognition of drug-associated environmental stimuli, retrieval of drug-associated memory, and drug-seeking behaviors is not fully understood. Methods Roles of dopamine neurotransmission in the prefrontal cortex (PFC) and nucleus accumbens (NAc) in the cocaine-conditioned place preference (CPP) paradigm were evaluated using in vivo microdialysis. Results In mice that had acquired cocaine CPP, dopamine levels in the PFC, but not in the NAc, increased in response to cocaine-associated cues when mice were placed in the cocaine chamber of an apparatus with 2 separated chambers. The induction of the dopamine response and the development of cocaine CPP were mediated through activation of glutamate NMDA (N-methyl-D-aspartate)/AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor signaling in the PFC during conditioning. Activation of dopamine D1 or D2 receptor signaling in the PFC was required for cocaine-induced locomotion, but not for the induction of the dopamine response or the development of cocaine CPP. Interestingly, dopamine levels in the NAc increased in response to cocaine-associated cues when mice were placed at the center of an apparatus with 2 connected chambers, which requires motivated exploration associated with cocaine reward. Conclusions Dopamine neurotransmission in the PFC is activated by the exposure to the cocaine-associated cues, whereas dopamine neurotransmission in the NAc is activated in a process of motivated exploration of cues associated with cocaine reward. Furthermore, the glutamate signaling cascade in the PFC is suggested to be a potential therapeutic target to prevent the progression of drug addiction.

Background This study explored the assessment of intrathoracic lymph node metastasis by 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography computed tomography (PET/CT) in patients with asbestos-related lung cancer (ARLC). Methods We retrospectively reviewed the data on 35 patients with ARLC who underwent preoperative FDG-PET/CT and surgical resection between January 2012 and December 2018. We collected medical information from medical records and imaging systems and examined the FDG uptake in each lymph nodal region resected by surgery and the presence or absence of pathological lymph node metastasis. Results Pathological lymph node metastases were detected in 14 (8.70%) of 161 nodal stations. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG-PET/CT were 71.4% (10/14), 87.8% (129/147), 35.7% (10/28), 97.0% (129/133), and 86.3% (139/161), respectively. Six of the eight false-positive patients had bilateral accumulations, whereas all six true-positive patients had unilateral accumulation (P=0.006). On histopathological examination, the false-positive nodes showed disruption of lymphoid follicles in the cortex, infiltration of histiocyte-like cells in the medulla, fibrous micronodules, and severe anthracosis. Conclusions PET/CT scans of patients with ARLC showed comparable sensitivity and specificity to those of PET/CT scans of patients with conventional lung cancer reported in the literature. Many false-positive cases also showed bilateral symmetric accumulation. This method can be used to evaluate lymph node involvement in lung cancer.

Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by overactivation of the complement alternative pathway. aHUS involves the presence of antibodies against complement factor H and its mutations in the complement genes. A 2-month-old boy presented with discoid rash, hemolytic anemia, thrombocytopenia, multiple antibodies, and hypocomplementemia with a very low level of C4 (< 3 mg/dL), indicating activation of the complement pathway, together fulfilling the systemic lupus erythematosus (SLE) criteria of the American College of Rheumatology at 5 months of age. However, most of these findings normalized spontaneously without any intervention. Further investigations revealed a high level of anti-complement factor H antibodies and a novel heterozygous missense mutation (p.Glu1172Ala, located in exon 22) in a complement gene, CFH. At 2 years of age, his SLE-like symptoms have not recurred, but hematuria and schistocytes were persistent. Eventually, aHUS was diagnosed rather than SLE. Our findings suggest that multiple antibody complex, including anti-complement factor H antibody, may temporarily activate the classical pathway, resulting in SLE-like findings.

Merkel cell carcinoma (MCC) of the breast is a very rare and aggressive type of neuroendocrine carcinoma of the breast (NECB) that typically occurs in older and immunocompromised individuals often presenting as a large palpable mass (Albright et al., 20181). Imaging features of MCC are similar to other NECBs, typically appearing as an oval circumscribed mass on mammography and as an irregular mass with increased vascularity on sonography (Jeon et al., 20142). While both MCC and primary NECB demonstrate positive immunostaining for synaptophysin, obtaining immunohistochemical stains for specific markers, such as CK7 and CK20 is imperative to confirm the diagnosis of MCC (Albright et al., 20181). We present a case of a 57-year-old female patient with no personal or family history of breast cancer, who presented for evaluation of a palpable abnormality in her left breast. Initial diagnostic mammogram demonstrated a circumscribed mass in the upper outer quadrant of the left breast corresponding to the palpable area of concern, which correlated to an irregular mass with increased vascularity on targeted ultrasound, similar to other NECBs. Pathologic results after tissue sampling yielded poorly differentiated primary NECB. Following neoadjuvant chemotherapy, the patient underwent a lumpectomy and further immunohistochemical stains of the lumpectomy specimen demonstrated diffusely positive synaptophysin, negative CK7, and positive CK20, consistent with MCC of the breast.

The management of congenital nephrotic syndrome of the Finnish type (CNF) is challenging. It is difficult to withdraw intravenous albumin infusions, resulting in long-term hospitalization. In addition, fatal hypotension after bilateral nephrectomy has been reported. In our center, we have performed unilateral nephrectomy during early infancy. Infants diagnosed with CNF between 2011 and 2020 in our institution were enrolled. We examined the clinical course before and after unilateral nephrectomy and evaluated the effectiveness of this strategy. Seven patients (all showing NPHS1 mutations) were enrolled. All required daily intravenous albumin infusion via central venous catheter (CVC). Unilateral nephrectomy was performed at a median of 76 days of age (59–208 days). Surgical complications did not occur in any of patients. The mean albumin dose was decreased after unilateral nephrectomy (2.0 vs 0.4 g/kg/day; p = 0.02). Intravenous albumin infusion could be withdrawn at a median of 17 days, the CVC removed at a median of 21 days, and they discharged at a median of 82 days after unilateral nephrectomy. Although bacterial infections were noted seven times before unilateral nephrectomy, only one episode occurred after surgery. Four patients initiated peritoneal dialysis at two to three years of age and all of them underwent kidney transplantation thereafter. Unilateral nephrectomy during early infancy may be an effective treatment allowing for withdrawal from albumin infusion, prevention of complications, withdrawal from CVCs and shortening hospital stay for patients with CNF.

A nighttime nap is expected to mitigate melatonin suppression during night work by blocking light input to the retina, but it is unclear. In the present study, we investigated the effects of a nap break on melatonin level, subjective sleepiness, and vigilance performance during simulated night work. Eleven healthy young males (mean +/- SD age: 22.2 +/- 4.1 years) participated in counterbalanced crossover design experiments with two conditions (nap vs. no nap). The subjects performed I 2-hour simulated night work from 21:00 to 09:00 h (illuminance: similar to 500 lx). Subjects with a nap condition took a nap for 2 hours in a dark room from 03:00, si bile subjects with a no nap condition continued the simulated night work. The results showed that immediately after the 2-h nap break, the melatonin level at 05:00 h temporarily recovered from light-induced melatonin suppression during the simulated night work but significantly suppressed again at 07:00 and 09:00 h. Subjective alertness and vigilance performance were impaired immediately after the nap break but subsequently enhanced. The results suggest that a single nap break for 2 hours could be a strategy to enhance alertness (luring the last part of night shift but inadequate for mitigating melatonin suppression.

Background: Aesthetics has become a major concern nowadays. Loss of interdental papilla in the anterior region of the oral cavity accounts for a major compromise in aesthetics. Thus, techniques to correct this defect has emerged as a new area of research in dentistry. The present study aims to compare reconstruction of the interdental papilla using subepithelial connective tissue graft (SCTG)and platelet rich fibrin (PRF). Material and Methods: The present randomised clinical trial included 36 patients equally divided into test (platelet rich fibrin) and control groups (subepithelial connective tissue graft). Papilla reconstruction was done and clinical parameters- contact point to interdental papilla distance (CPID), width of keratinized gingiva (WKG), plaque index (PI), gingival index (GI), papillary bleeding index (PBI), pocket depth (PPD) were recorded at baseline, 3 and 6 months. Healing index (HI) was recorded at 1, 2 and 3 weeks. Results: At the end of 6 months, it was found that interdental papillae fill in terms of decrease in distance from the contact point to the interdental papilla tip and gain in WKG was statistically significant in both the groups (p value ≤0.05). On intergroup comparison, however, it was found that the improvement in the abovementioned parameters was significantly greater in the control group (39.32%) as compared to the test group (14.79%). The difference in other clinical parameters at various time intervals were found to be nonsignificant.

Background: Here we present a retrospective study of 17 cases in which the ovary on the affected side was spared in fertility-sparing surgery (FSS) during treatment for ovarian borderline malignant or malignant tumor. We determine that cystectomy is a suitable treatment for ovarian borderline tumors. Methods: A retrospective observation study was conducted at Saiseikai Fukuoka General Hospital in Japan between April 2009 and September 2020. Our hospital experienced 89 cases of FSS during treatment for ovarian borderline or malignant tumor. Of those, there were 17 cases in which the ovary on the affected side was spared. We examined recurrent and pregnant cases by stage, preoperative diagnosis, intraoperative pathological diagnosis, postoperative pathological diagnosis, and adjuvant therapy. Result: Of the 17, 12 cases were borderline malignant tumor, 4 were immature teratoma grade 1 (G1), and 1 case was endometrioid adenocarcinoma G1. Rapid intraoperative pathological diagnosis was conducted in 9 of the cases, and there were 6 in which surgical method was chosen based on the aforementioned results. Laparoscopic surgery was performed in 2 cases in which tumors were deemed benign via preoperative diagnosis, 2 cases of mature teratoma, and 2 in which borderline ovarian tumor was suspected. One (1) case of paraovarian cystecomy in a patient with history of multiple cesarean sections turned out to be serous borderline tumor. Postoperative treatment took place in only 1 case: endometrioid adenocarcinoma. There were 2 cases of recurrence, and 4 cases were eventually able to become pregnant naturally post-surgery. These pregnant cases included 1 in which serous borderline tumor recurred and we performed both cystectomy and lymphadenectomy, and one in which chemotherapy was performed after cyst enucleation for endometrioid adenocarcinoma G1. Conclusion: At present, there is no clear policy for FSS in cases such as stage Ib in which there are bilateral tumors. Accordingly, in the current study a radiologist was consulted for preoperative diagnosis, and surgical method was chosen with a view towards possible borderline malignancy or malignancy. In cases where fertility preservation of the affected ovary is a high priority, it is crucial to clearly explain the possibility of recurrence to the patient. We also stress the importance of detailed consultation among the surgical team during rapid intraoperal frozen section pathological examination for making the appropriate decision to ensure fertility preservation mid-surgery.

It is difficult to perform intestinal anastomosis in low-birth-weight infants because the intestinal diameter is small and the discrepancy in diameter of the proximal and distal intestines is often large, but there has been no optimal-sized training model. Therefore, we developed a new intestinal anastomosis training model that imitated the size of the intestine in low-birth-weight infants, and evaluated its face and construct validity. Two intestinal models were developed with crossMedical, Inc. using a hydrophilic acrylic material (wet model) or a polyurethane soft resin (dry model). The inner diameter of the simulated intestinal tract was 15 mm on the oral end and 6 mm on the anal end. Thirteen pediatric surgeons performed anastomosis and responded to the questionnaire. In the questionnaire, the wet model had significantly higher scores than the dry model in “appearance”, “softness” and “usefulness for training”. In the anastomotic results of the wet model, the anastomosis leak pressure was significantly correlated with the number of intestinal anastomotic experiences in low-birth-weight infants (correlation coefficient = 0.64, P = 0.035). The wet-type intestinal anastomosis model showed good face validity. Its leak pressure had a significant correlation with clinical experience; thus, construct validity was demonstrated.

To investigate the energy and macronutrient bioaccessibility of almonds in individuals with hyperlipidemia.In a previously reported randomized crossover trial, men and postmenopausal women with hyperlipidemia incorporated 3 isoenergetic supplements into a National Cholesterol Education Program Step 2 diet for 1 month each between September 20, 2000, and June 27, 2001. Supplements provided consisted of full-dose almonds (73±5 g/d), half-dose almonds (38±3 g/d) plus half-dose muffins, and full-dose muffins (control). Energy and macronutrients, including individual fatty acids, were measured in the dietary supplements and fecal samples using gas chromatography and Association of Official Analytical Chemists methods. Serum was measured for lipids and fatty acids. Bioaccessibility of energy and macronutrients from almond consumption was assessed from dietary intake (7-day food records) and fecal output.Almond-related energy bioaccessibility was 78.5%±3.1%, with an average energy loss of 21.2%±3.1% (40.6 kcal/d in the full-dose almond phase). Bioaccessibility of energy and fat from the diet as a whole was significantly less with almond consumption (in both half- and full-dose phases) compared with the control. Bioaccessibility of fat was significantly different between treatment phases (P.001) and on average lower by 5.1% and 6.3% in the half- and full-dose almond phases, respectively, compared with the control phase. Energy bioaccessibility was significantly different between the treatment phases (P=.02), decreasing by approximately 2% with the inclusion of the full dose of almonds compared with the control.Energy content of almonds may not be as bioaccessible in individuals with hyperlipidemia as predicted by Atwater factors, as suggested by the increased fat excretion with almond intake compared with the control.ClinicalTrials.gov identifier: NCT00507520.

Background The long-term prognostic impact of IVUS findings following Absorb BVS implantation remains uncertain. This study aimed to identify the IVUS predictors of long-term clinical outcomes following ABSORB bioresorbable vascular scaffold (BVS) implantation from the pooled IVUS substudy cohorts of the ABSORB III and Japan trials. Methods A total of 298 lesions in 286 patients were enrolled with 2:1 randomization to ABSORB BVS vs. cobalt-chromium everolimus-eluting stents. This sub-analysis included 168 lesions of 160 patients in the Absorb arm whose post-procedural quantitative IVUS were available. The primary endpoint of this analysis was device-oriented composite endpoint (DOCE) of target lesion failure, including cardiac death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization. The median follow-up duration was 4.9 [3.1–5.0] years. Results During follow-up, DOCE occurred in 10.1% of lesions treated with Absorb BVS. Among several post-procedural IVUS indices associated with DOCE, non-uniform device expansion (defined as uniformity index = minimum / maximum device area) (hazard ratio 0.47 per 0.1 increase [95%CI 0.28 to 0.77]; p = 0.003) and residual reference plaque burden (hazard ratio 4.01 per 10% increase [95%CI 1.50 to 10.77]; p = 0.006) were identified as independent predictors of DOCE by Cox multivariable analysis. Conclusions Nonuniform device expansion and substantial untreated residual plaque in reference segments were associated with long-term adverse events following BVS implantation. Baseline imaging to identify the appropriate device landing zone and procedural imaging to achieve uniform device expansion if possible (e.g. through post-dilatation) may improve clinical outcomes of BVS implantation. Clinical trial registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01751906 (ABSORB III); NCT01844284 (ABSORB Japan).