Redundant function of the Arabidopsis phosphatidylinositol 4-phosphate 5-kinase genes PIP5K4-6 is essential for pollen germination.

Phosphatidylinositol 4-phosphate 5-kinase (PIP5K) is a key enzyme producing the signaling lipid phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2 ] in eukaryotes. Although PIP5K genes are reported to be involved in pollen tube germination and growth, the essential roles of PIP5K in these processes remain unclear. Here, we performed a comprehensive genetic analysis of the Arabidopsis thaliana PIP5K4, PIP5K5, and PIP5K6 genes and revealed that their redundant function is essential for pollen germination. Pollen with the pip5k4pip5k5pip5k6 triple mutation was sterile, while pollen germination efficiency and pollen tube growth were reduced in the pip5k6 single mutant and further reduced in the pip5k4pip5k6 and pip5k5pip5k6 double mutants. YFP-fusion proteins, PIP5K4-YFP, PIP5K5-YFP, and PIP5K6-YFP, which could rescue the sterility of the triple mutant pollen, preferentially localized to the tricolpate aperture area and the future germination site on the plasma membrane prior to germination. Triple mutant pollen grains under the germination condition, in which spatiotemporal localization of the PtdIns(4,5)P2 fluorescent marker protein 2xmCHERRY-2xPHPLC as seen in the wild type was abolished, exhibited swelling and rupture of the pollen wall, but neither the conspicuous protruding site nor site-specific deposition of cell wall materials for germination. These data indicate that PIP5K4-6 and their product PtdIns(4,5)P2 are essential for pollen germination, possibly through the establishment of the germination polarity in a pollen grain.

Assessment of abnormal transvalvular flow and wall shear stress direction for pediatric/young adults with bicuspid aortic valve: a cross-sectional 4D flow study.

BACKGROUND: Aortic dilation is seen in pediatric/young adult patients with bicuspid aortic valve (BAV), and hemodynamic markers to predict aortic dilation are necessary for monitoring. Although promising hemodynamic metrics, such as abnormal wall shear stress (WSS) magnitude, have been proposed for adult BAV patients using 4D flow cardiovascular magnetic resonance, those for pediatric BAV patients have less frequently been reported, partly due to scarcity of data to define normal WSS range. To circumvent this challenge, this study aims to investigate if a recently proposed 4D flow-based hemodynamic measurement, abnormal flow directionality, is associated with aortic dilation in pediatric/young adult BAV patients. METHODS: 4D flow scans for BAV patients (<20 years old) and age-matched controls were retrospectively enrolled. Static segmentation for the aorta and pulmonary arteries was obtained to quantify peak systolic hemodynamics and diameters in the proximal aorta. In addition to peak velocity, wall shear stress (WSS), vorticity, helicity, and viscous energy loss, direction of aortic velocity and WSS in BAV patients was compared with that of control atlas using registration technique; angle differences of >60deg and >120deg were defined as moderately and severely abnormal, respectively. Association between the obtained metrics and normalized diameters (Z-scores) were evaluated at the sinotubular junction, mid ascending aorta, and distal ascending aorta. RESULTS: Fifty-three BAV patients, including eighteen with history of repaired aortic coarctation, and seventeen controls were enrolled. Correlation between moderately abnormal velocity/WSS direction and aortic Z-scores was moderate to strong at the sinotubular junction and mid ascending aorta (R=0.62-0.81; p<0.001) while conventional measurements exhibited weaker correlation (|R|=0.003-0.47, p=0.009-0.99) in all subdomains. Multivariable regression analysis found moderately abnormal velocity direction and existence of aortic regurgitation (only for isolated BAV group) were independently associated with mid ascending aortic Z-scores. CONCLUSION: Abnormal velocity and WSS directionality in the proximal aorta was strongly associated with aortic Z-scores in pediatric/young adult BAV patients.

Outcomes of a bypass-first strategy in chronic limb-threatening ischemia based on the Global Vascular Guidelines.

OBJECTIVE: The Global Vascular Guidelines (GVGs) recommend initial revascularization (bypass or endovascular therapy) for chronic limb-threatening ischemia (CLTI) based on anatomical complexity and limb severity. This decision is made based on a prediction of the outcomes after endovascular intervention. This study was performed to evaluate outcomes after distal bypass in cases recommended for GVG bypass. METHODS: A total of 239 distal bypasses for CLTI were evaluated in 195 patients with a GVG bypass recommendation treated between 2009 and 2020 at a single center in Japan. Comparisons were made between crural and pedal bypass cases. RESULTS: The 195 patients (median age, 77 years; 67% male) underwent 133 crural bypasses (106 patients; 54%) and 106 pedal bypasses (89 patients; 46%). Hemodialysis was more common in pedal cases than in crural cases (P = .03). Hospital deaths occurred in two cases (1%) within 30 days. The whole cohort has a follow-up rate of 96% over a mean of 28 ± 26 months, with 3-year limb salvage rates of 87% and 3-year primary, assisted primary, and secondary patency rates of 40%, 65%, and 67%, all without significant differences between crural and pedal cases. The 1-year wound healing rate was 88% and tended to be higher in crural cases than in pedal cases (P = .068). The 3-year survival rate was 52% in the cohort and did not differ significantly between crural and pedal cases. CONCLUSIONS: Patients with CLTI with a GVG bypass recommendation had acceptable limb salvage, graft patency, wound healing, and survival after distal bypass, regardless of the bypass method. These findings indicate that a GVG bypass recommendation as an initial revascularization method is valid in the real world.

Reference Values for Fetal Cardiac Dimensions, Volumes, Ventricular Function and Left Ventricular Longitudinal Strain Using Doppler Ultrasound Gated Cardiac Magnetic Resonance Imaging in Healthy Third Trimester Fetuses.

BACKGROUND: Recent advances in hardware and software permit the use of cardiac MRI of late gestation fetuses, however there is a paucity of MRI-based reference values. PURPOSE: To provide initial data on fetal cardiac MRI-derived cardiac dimensions, volumes, ventricular function, and left ventricular longitudinal strain in healthy developing fetuses >30 weeks gestational age. STUDY TYPE: Prospective. POPULATION: Twenty-five third trimester (34 ± 1 weeks, range of 32-37 weeks gestation) women with healthy developing fetuses. FIELD STRENGTH/SEQUENCE: Studies were performed at 1.5 T and 3 T. Cardiac synchronization was achieved with a Doppler ultrasound device. The protocol included T2 single shot turbo spin echo stacks for fetal weight and ultrasound probe positioning, and multiplanar multi-slice cine balanced steady state free precession gradient echo sequences. ASSESSMENT: Primary analyses were performed by a single observer. Weight indexed right ventricular (RV) and left ventricular (LV) volumes and function were calculated from short axis (SAX) stacks. Cardiac dimensions were calculated from the four-chamber and SAX stacks. Single plane LV longitudinal strain was calculated from the four-chamber stack. Interobserver variability was assessed in 10 participants. Cardiac MRI values were compared against available published normative fetal echocardiogram data using z-scores. STATISTICAL TESTS: Mean and SDs were calculated for baseline maternal/fetal demographics, cardiac dimensions, volumes, ventricular function, and left ventricular longitudinal strain. Bland-Altman and intraclass correlation coefficient analysis was performed to test interobserver variability. RESULTS: The mean gestational age was 34 ± 1.4 weeks. The mean RV and LV end diastolic volumes were 3.1 ± 0.6 mL/kg and 2.4 ± 0.5 mL/kg respectively. The mean RV cardiac output was 198 ± 49 mL/min/kg while the mean LV cardiac output was 173 ± 43 mL/min/kg. DATA CONCLUSION: This paper reports initial reference values obtained by cardiac MRI in healthy developing third trimester fetuses. MRI generally resulted in slightly larger indexed values (by z-score) compared to reports in literature using fetal echocardiography. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Effectiveness of the Vascular Quality Initiative Chronic Limb-Threatening Ischemia Mortality Prediction Model in Patents with Distal Bypass.

BACKGROUND: The purpose of this study is to evaluate the effectiveness of mortality prediction using the Vascular Quality Initiative (VQI) chronic limb-threatening ischemia (CLTI) model in patients with distal bypass. METHODS: Patients who underwent distal bypass for CLTI from 2009 to 2020 at a single center were retrospectively reviewed. Distal bypass was defined as any bypass with a distal anastomosis to the posterior tibial, anterior tibial, dorsalis pedis, plantar, or peroneal artery. Baseline characteristics, operative details, hospital outcomes, and medium-term outcomes were compared among patients with a low-, medium-, and high-risk of mortality based on a VQI CLTI calculation. The primary endpoints were survival and limb salvage. RESULTS: A total of 287 distal bypasses were performed in 230 patients (153 males; median age, 74 years; diabetes mellitus, 70%; end-stage renal disease [ESRD] with hemodialysis, 38%). These patients were stratified into 153 (66%) low-, 35 (15%) medium-, and 42 (18%) high-risk cases based on the VQI CLTI model. There were two hospital deaths (1%) within 30 days. During a mean follow-up period of 33 ± 29 months, 105 patients died and 26 limbs (9%) required major amputation. The 2-year survival rate of 81% in the low-risk group was significantly higher than those of 41% in the medium-risk group and 46% in the high-risk group (both P < 0.001). The 2-year survival rates did not differ significantly between the medium- and high-risk groups (P = 0.81). The 2-year limb salvage rate of 93% in the low-risk group was significantly higher than those of 81% in the medium-risk (P = 0.023) and those of 87% in the high-risk (P = 0.039) groups. There were no significant differences in graft patency and wound healing among the three groups. CONCLUSIONS: These results suggest that distal bypass is optimal treatment for patients with a low VQI-predicted risk of mortality. However, the lower limb salvage and higher mortality rates at 2 years suggest that the decision-making for VQI medium- and high-risk patients may be carefully considered.

Parathyroid carcinoma: impact of preoperative diagnosis on the choice of surgical procedure.

The operative procedure in the surgical treatment of parathyroid carcinoma differs from that of benign hyperparathyroidism. However, preoperative differentiation is often difficult. This study elucidated how clinicians diagnose parathyroid carcinoma and the relationship between preoperative diagnosis and the operative course. Using a retrospective chart review, twenty cases of parathyroid carcinoma from nine participating centers were examined. In 11 cases with preoperative suspicion of malignancy, at least one of these three features was found: elevated serum calcium level (>14 mg/dL), palpable mass, and irregular margin on ultrasonography. Although an intact parathyroid hormone (iPTH) threshold to suspect malignancy has not been established, six cases showed marked iPTH elevation exceeding 8.0 times the upper limit of normal. One case was excluded from analysis due to hemodialysis. Compared with the four cases that showed calcium elevation, the iPTH threshold might represent better sensitivity. Among 9 cases of benign preoperative diagnosis, six cases were performed with pericapsular resection. In three cases where malignancy was suspected in the middle of the operation, the recommended en bloc resection with ipsilateral thyroid lobectomy was not performed but a parathyroidectomy with surrounding soft tissue. In contrast, 10 preoperatively suspected cases underwent en bloc resection, and one case underwent pericapsular resection followed by supplementary ipsilateral hemithyroidectomy due to the uncertain pre- and intraoperative findings to determine the diagnosis. In conclusion, the surgical procedure for parathyroid carcinoma strongly depends on the preoperative diagnosis. The presence of excessive iPTH levels might contribute to improved preoperative diagnostic sensitivity for parathyroid carcinoma.

Segmentation of the Aorta and Pulmonary Arteries Based on 4D Flow MRI in the Pediatric Setting Using Fully Automated Multi-Site, Multi-Vendor, and Multi-Label Dense U-Net.

BACKGROUND: Automated segmentation using convolutional neural networks (CNNs) have been developed using four-dimensional (4D) flow magnetic resonance imaging (MRI). To broaden usability for congenital heart disease (CHD), training with multi-institution data is necessary. However, the performance impact of heterogeneous multi-site and multi-vendor data on CNNs is unclear. PURPOSE: To investigate multi-site CNN segmentation of 4D flow MRI for pediatric blood flow measurement. STUDY TYPE: Retrospective. POPULATION: A total of 174 subjects across two sites (female: 46%; N = 38 healthy controls, N = 136 CHD patients). Participants from site 1 (N = 100), site 2 (N = 74), and both sites (N = 174) were divided into subgroups to conduct 10-fold cross validation (10% for testing, 90% for training). FIELD STRENGTH/SEQUENCE: 3 T/1.5 T; retrospectively gated gradient recalled echo-based 4D flow MRI. ASSESSMENT: Accuracy of the 3D CNN segmentations trained on data from single site (single-site CNNs) and data across both sites (multi-site CNN) were evaluated by geometrical similarity (Dice score, human segmentation as ground truth) and net flow quantification at the ascending aorta (Qs), main pulmonary artery (Qp), and their balance (Qp/Qs), between human observers, single-site and multi-site CNNs. STATISTICAL TESTS: Kruskal-Wallis test, Wilcoxon rank-sum test, and Bland-Altman analysis. A P-value <0.05 was considered statistically significant. RESULTS: No difference existed between single-site and multi-site CNNs for geometrical similarity in the aorta by Dice score (site 1: 0.916 vs. 0.915, P = 0.55; site 2: 0.906 vs. 0.904, P = 0.69) and for the pulmonary arteries (site 1: 0.894 vs. 0.895, P = 0.64; site 2: 0.870 vs. 0.869, P = 0.96). Qs site-1 medians were 51.0-51.3 mL/cycle (P = 0.81) and site-2 medians were 66.7-69.4 mL/cycle (P = 0.84). Qp site-1 medians were 46.8-48.0 mL/cycle (P = 0.97) and site-2 medians were 76.0-77.4 mL/cycle (P = 0.98). Qp/Qs site-1 medians were 0.87-0.88 (P = 0.97) and site-2 medians were 1.01-1.03 (P = 0.43). Bland-Altman analysis for flow quantification found equivalent performance. DATA CONCLUSION: Multi-site CNN-based segmentation and blood flow measurement are feasible for pediatric 4D flow MRI and maintain performance of single-site CNNs. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

An Evaluation of Pre-Operative Nutritional Assessment Methods in Patients with Chronic Limb Threatening Ischaemia Having Distal Bypass.

OBJECTIVE: The purpose of this study was to evaluate the influence of pre-operative nutritional status on long term outcomes of patients with chronic limb threatening ischaemia (CLTI) after distal bypass. METHODS: Patients who underwent distal bypass for CLTI from 2011 to 2020 at a single centre were reviewed retrospectively in Japan. Comparisons were made between patients with malnutrition and normal nutrition, as diagnosed by four nutritional assessments: Controlling Nutritional Status (CONUT), Geriatric Nutritional Risk Index (GNRI), Glasgow Prognostic Score (GPS), and Prognostic Nutritional Index (PNI). The primary endpoint was survival, and the secondary endpoints were graft patency, limb salvage, and wound healing. RESULTS: A total of 314 distal bypasses were performed in 249 patients (169 males; median age, 76 years; diabetes mellitus, 70%; and end stage renal disease with haemodialysis, 40%). Malnutrition was observed in 103 patients (41%) evaluated by CONUT, 129 (52%) by GNRI, 76 (31%) by GPS, and 114 (46%) by PNI. The survival rates in the study cohort were 81% at one year, 55% at three years, and 47% at five years. Malnutrition in all assessments was statistically significantly associated with reduced survival rate (CONUT, p < .001; GNRI, p = .002; GPS, p < .001; PNI, p < .001). In multivariable analysis, CONUT was the best predictor of mortality (p = .014). Malnutrition did not affect graft patency and limb salvage, but malnutrition based on CONUT, GNRI, and GPS was statistically significantly associated with reduced wound healing (CONUT, p = .002; GNRI, p = .006; GPS, p = .011). In multivariable analysis, CONUT tended to be the best predictor of wound healing (p = .061). CONCLUSION: Malnutrition in patients with CLTI with distal bypass was associated with overall mortality and incomplete wound healing. CONUT assessment was most effective for prediction of survival and wound healing. Distal bypass for CLTI patients with malnutrition may be suboptimal, and endovascular treatment may be recommended as an initial revascularisation method.

Prognostic Significance of Intraoperative Graft Flow in Distal Bypass on Long-Term Outcomes in Patients with Chronic Limb-Threatening Ischemia.

BACKGROUND: The aim of the study was to determine the prognostic significance of measurement of graft flow on the patency of distal bypass. METHODS: A retrospective analysis was performed for 208 distal bypasses (208 limbs, 170 patients) with a single segment great saphenous vein conducted in a nonreversed manner from January 2009 to December 2019 in Japan. Patient backgrounds, operative details (including intraoperative mean graft flow), hospital outcomes, and long-term outcomes were evaluated. The primary endpoints were the primary, assisted primary, and secondary patency of the distal bypass graft and the secondary endpoints were limb salvage and wound healing. RESULTS: The median intraoperative graft flow was 18 [10-30] mL/min. The follow-up rate was 98% in a mean follow-up period of 31 ± 26 months. Primary, assisted primary, and secondary patency in the cohort were 51%, 72%, and 73% at 1 year, and 39%, 59%, and 61% at 3 years, respectively. In multivariate analysis, the independent risk factors for primary patency were low graft flow (P = 0.0022) and female sex (P = 0.0016), and those for secondary patency were also low graft flow (P = 0.0025) and female sex (P < .001). The cut-offs for graft flow predicting primary and secondary patency were both 16 mL/min. The limb salvage rate was 94% at 1 year and 89% at 3 years; and the wound healing rates were 55%, 71% and 84% at 3, 6, and 12 months, respectively. Limb salvage and wound healing were not significantly associated with intraoperative graft flow. CONCLUSIONS: Intraoperative graft flow was an independent predictor for graft patency in distal bypass, but had no influence on limb salvage and wound healing. The cut-off value for the mean graft flow predicting primary and secondary patency was 16 mL/min.

Free-breathing magnetic resonance imaging with radial k-space sampling for neonates and infants to reduce anesthesia.

BACKGROUND: Conventional chest and abdominal MRI require breath-holds to reduce motion artifacts. Neonates and infants require general anesthesia with intubation to enable breath-held acquisitions. OBJECTIVE: We aimed to validate a free-breathing approach to reduce general anesthesia using a motion-insensitive radial acquisition with respiratory gating. MATERIALS AND METHODS: We retrospectively enrolled children <3 years old who were referred for MRI of the chest or abdomen. They were divided into two groups according to MRI protocol: (1) breath-held scans under general anesthesia with T2-weighted single-shot fast spin-echo (SSFSE) and contrast-enhanced T1-weighted modified Dixon, and (2) free-breathing scans using radial sequences (T2-W MultiVane XD and contrast-enhanced T1-W three-dimensional [3-D] Vane XD). Two readers graded image quality and motion artifacts. RESULTS: We included 23 studies in the free-breathing cohort and 22 in the breath-hold cohort. The overall imaging scores for the free-breathing radial T2-W sequence were similar to the scores for the breath-held T2-W SSFSE sequence (chest, 3.6 vs. 3.2, P=0.07; abdomen, 3.9 vs. 3.7, P=0.66). The free-breathing 3-D radial T1-W sequence also had image quality scores that were similar to the breath-held T1-W sequence (chest, 4.0 vs. 3.0, P=0.06; abdomen, 3.7 vs. 3.9, P=0.15). Increased motion was seen in the abdomen on the radial T2-W sequence (P<0.001), but increased motion was not different in the chest (P=0.73) or in contrast-enhanced T1-W sequences (chest, P=0.39; abdomen, P=0.15). The mean total sequence time was longer in free-breathing compared to breath-held exams (P<0.01); however, this did not translate to longer overall exam times (P=0.94). CONCLUSION: Motion-insensitive radial sequences used for infants and neonates were of similar image quality to breath-held sequences and had decreased sedation and intubation.

Detailed analyses of the crucial functions of Zn transporter proteins in alkaline phosphatase activation.

Numerous zinc ectoenzymes are metalated by zinc and activated in the compartments of the early secretory pathway before reaching their destination. Zn transporter (ZNT) proteins located in these compartments are essential for ectoenzyme activation. We have previously reported that ZNT proteins, specifically ZNT5-ZNT6 heterodimers and ZNT7 homodimers, play critical roles in the activation of zinc ectoenzymes, such as alkaline phosphatases (ALPs), by mobilizing cytosolic zinc into these compartments. However, this process remains incompletely understood. Here, using genetically-engineered chicken DT40 cells, we first determined that Zrt/Irt-like protein (ZIP) transporters that are localized to the compartments of the early secretory pathway play only a minor role in the ALP activation process. These transporters included ZIP7, ZIP9, and ZIP13, performing pivotal functions in maintaining cellular homeostasis by effluxing zinc out of the compartments. Next, using purified ALP proteins, we showed that zinc metalation on ALP produced in DT40 cells lacking ZNT5-ZNT6 heterodimers and ZNT7 homodimers is impaired. Finally, by genetically disrupting both ZNT5 and ZNT7 in human HAP1 cells, we directly demonstrated that the tissue-nonspecific ALP-activating functions of both ZNT complexes are conserved in human cells. Furthermore, using mutant HAP1 cells, we uncovered a previously-unrecognized and unique spatial regulation of ZNT5-ZNT6 heterodimer formation, wherein ZNT5 recruits ZNT6 to the Golgi apparatus to form the heterodimeric complex. These findings fill in major gaps in our understanding of the molecular mechanisms underlying zinc ectoenzyme activation in the compartments of the early secretory pathway.

Lamotrigine in the maintenance treatment of bipolar disorder.

BACKGROUND: Bipolar disorder is a chronic mental disorder with repetitive mania/hypomania as well as depressive episodes, which eventually results in marked impairment in overall functioning and health-related quality of life.  A worldwide prevalence rate of 2.4% has been reported. The risk of suicide is higher in people with bipolar disorder than those with other mental disorders. Therefore, effective management of bipolar disorder in the maintenance period is warranted to minimize the risk of relapse or recurrence. Although lithium has been the standard treatment of bipolar disorder for many years, it is associated with adverse effects and teratogenicity. Lamotrigine is approved to be expected for prevention of recurrence for the maintenance treatment of bipolar disorder. In addition, lamotrigine is as effective as lithium. Therefore, we performed a systematic review to confirm the efficacy and safety of lamotrigine in the maintenance treatment of bipolar disorder. OBJECTIVES: To assess the efficacy and tolerability of lamotrigine in the maintenance treatment of bipolar disorder. SEARCH METHODS: We searched Ovid MEDLINE, Embase, PsycINFO, the Cochrane Common Mental Disorders Group's Specialized Register (CCMDCTR) and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to 21 May 2021. We also searched international trial registries and contacted experts in the field. SELECTION CRITERIA: We included randomized controlled trials enrolling adults with bipolar disorder who were treated with lamotrigine, placebo or lithium. DATA COLLECTION AND ANALYSIS: Two reviews authors independently checked the eligibility of studies and extracted data using a standardized form. Data extracted included study characteristics, participant characteristics, intervention details, settings, and outcome measures in the term of efficacy and tolerability. Study information were then entered into RevMan web. MAIN RESULTS: We included 11 studies with a total of 2314 participants in this review; 1146 were randomized to lamotrigine, 869 were randomized to placebo and, 299 to lithium. We rated all studies as having an unclear risk of bias in at least one domain of Cochrane's tool for assessing risk of bias, with the most commonly observed weakness being selection bias (random sequence generation and allocation concealment). We judged five studies to be at a high risk of detection bias (blinding of outcome assessment). These potential biases pose as major threat to the validity of the included studies in this review. Outcomes of efficacy showed a possible advantage of lamotrigine over placebo. The estimated risk ratio (RR) for recurrence of manic symptom at one year as measured by the Young Mania Rating Scale (YMRS) was 0.67, (95% confidence interval (CI) 0.51 to 0.87; 3 studies, 663 participants; low-certainty evidence) in favor of lamotrigine. The RR of clinical worsening with the need for additional psychotropic treatment (RR 0.82, 95% CI 0.70 to 0.98; 4 studies, 756 participants) based on moderate-certainty evidence. The possible benefits of lamotrigine were also seen for the outcome of treatment withdrawal due to any reason at 6-12 months after treatment (RR 0.88, 95% CI 0.78 to 0.99; 4 studies, 700 participants; moderate-certainty evidence). Regarding tolerability, our analyses showed that the incidence rates of adverse effects were similar between the lamotrigine group and the placebo group (short-term effect: RR 1.07, 95% CI 0.81 to 1.42; 5 studies, 1138 participants; very low-certainty evidence; long-term effect: RR 0.97, 95% CI 0.77 to 1.23; 4 studies, 756 participants; moderate-certainty evidence). In the comparison between lamotrigine and lithium, efficacy was similar between groups except for recurrence of mania episode at one year. Recurrence of manic symptoms was higher in the lamotrigine group than that of the lithium group (RR 2.13, 95% CI 1.32 to 3.44; 3 studies, 602 participants; moderate-certainty evidence). Analysis of adverse effects at 6-12 months showed that a lower proportion of participants experienced at least one adverse effect when treated with lamotrigine compared to lithium (RR 0.70, 95% CI 0.51 to 0.96; 4 studies, 691 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Low- to moderate-certainty evidence collectively suggests that lamotrigine may be superior to placebo as a treatment modality for bipolar disorder. In comparison to lithium, people with bipolar disorder seem to tolerate lamotrigine better in the long run; however, the demonstrated efficacy in the maintenance of bipolar disorder was similar between the two groups.

Use of compressed sensing to reduce scan time and breath-holding for cardiac cine balanced steady-state free precession magnetic resonance imaging in children and young adults.

BACKGROUND: Conventional pediatric volumetric MRI acquisitions of a short-axis stack typically require multiple breath-holds under anesthesia. OBJECTIVE: Here, we aimed to validate a vendor-optimized compressed-sensing approach to reduce scan time during short-axis balanced steady-state free precession (bSSFP) cine imaging. MATERIALS AND METHODS: Imaging was performed in 28 patients (16±9 years) in this study on a commercial 3-tesla (T) scanner using retrospective electrocardiogram-gated cine bSSFP. Cine short-axis images covering both ventricles were acquired with conventional parallel imaging and a vendor-optimized parallel imaging/compressed-sensing approach. Qualitative Likert scoring for blood-myocardial contrast, edge definition, and presence of artifact was performed by two experienced radiologists. Quantitative comparisons were performed including biventricular size and function. A paired t-test was used to detect significant differences (P<0.05). RESULTS: Scan duration was 7±2 s/slice for conventional imaging (147±33 s total) vs. 4±2 s/slice for compressed sensing (83±28 s total). No significant differences were found with qualitative image scores for blood-myocardial contrast, edge definition, and presence of artifact. No significant differences were found in volumetric analysis between the two sequences. The number of breath-holds was 10±4 for conventional imaging and 5±3 for compressed sensing. CONCLUSION: Compressed sensing allowed for a 50% reduction in the number of breath-holds and a 43% reduction in the total scan time without differences in the qualitative or quantitative measurements as compared to the conventional technique.

Effectiveness of combined superficial femoral artery endovascular therapy with popliteal-to-distal bypass: A paradigm shift in surgical open bypass for chronic limb-threatening ischemia.

OBJECTIVES: The purpose of this study was to evaluate the results of combining superficial femoral artery endovascular therapy with distal bypass originating from the popliteal artery as a method of lower extremity revascularization in patients with chronic limb-threatening ischemia. METHODS: The records of patients undergoing combined superficial femoral artery endovascular therapy with popliteal-to-distal bypass for chronic limb-threatening ischemia from January 2014 to April 2020 at a single institution were retrospectively reviewed. The patients' background, operative details, and long-term outcomes were analyzed. RESULTS: Fifty-two popliteal-to-distal bypasses with superficial femoral artery endovascular therapy were performed in 49 patients (33 men; mean age, 76 ± 9 years; diabetes mellitus, 80%; end-stage renal disease with hemodialysis, 47%). The Trans-Atlantic Inter-Society Consensus II classification of superficial femoral artery-popliteal lesion was "A" in 8 (15%) patients, "B" in 14 (27%) patients, "C" in 24 (46%) patients, and "D" in 6 (12%) patients. The intervention for superficial femoral artery lesions was plain old balloon angioplasty in 4 patients, self-expandable nitinol stent in 15 patients, drug-coated balloon in 18 patients, drug-eluting stent in 4 patients, stent graft in 10 patients, and interwoven nitinol stent in 1 patient. Distal bypass originated from the above-knee popliteal artery in 9 (17%) limbs and the below-knee popliteal artery in 43 (83%) limbs. The most common outflow artery was the posterior tibial artery (44%). The mean follow-up period was 17 ± 17 months. The primary and secondary patency of the graft was 44% and 72%, respectively, at 1 year and 39% and 72%, respectively, at 3 years. Primary patency and freedom from clinical-driven target lesion revascularization of superficial femoral artery endovascular therapy lesions were 85% and 90%, respectively, at 1 year and 63% and 75%, respectively, at 3 years. Limb salvage was 97% at 1 year and 92% at 3 years. Wound healing was 67% at 6 months and 83% at 12 months. CONCLUSIONS: Combined superficial femoral artery endovascular therapy with popliteal-to-distal bypass may be a promising approach for patients with chronic limb-threatening ischemia because of durable patency, acceptable wound healing, and good limb salvage.

A model six-month workshop for developing systematic review protocols at teaching hospitals: action research and scholarly productivity.

BACKGROUND: Research engagement contributes to the improvement of patient care. A systematic review is a suitable first scholarly activity because it entails summarization of publicly available data and usually requires neither rigorous ethical review nor research funding. METHODS: This study aimed to develop a model workshop for healthcare staff to acquire skills in creating systematic review protocols based on their own clinical questions at teaching hospitals. We used an action research method to create a model workshop at four hospitals in Japan from April 2015 to March 2017. To improve the program, we solicited reflections using participant questionnaires for each lecture and examined the quality of homework submitted by participants after each lecture. We administered a revised final version of the workshop at five hospitals from April 2016 to March 2017. We evaluated the participants' scholarly productivity related to these workshops. The observation period was a minimum of 2 years following the workshops. RESULTS: Most participants had never developed a formal clinical research protocol and voluntarily participated in the workshop. The action research was developed and implemented at nine teaching hospitals in Japan, including one university hospital. The study developed a model nine-step workshop curriculum: 1) Research question development, 2) Search strategy development, 3) Search strategy brush-up, 4) Exclusion and inclusion criteria development, 5) Risk of bias assessment planning, 6) Meta-analysis planning, 7) Subgroup and sensitivity analysis planning, 8) Planning the presentation of results, and 9) Presentation protocols. A total of 233 participants, including medical doctors and other health professionals, produced 414 research questions. Seventy-nine participants (34%) completed the workshop, and 47 review teams accomplished systematic review protocols. The participants published 13 peer-reviewed articles as a result of the workshop. CONCLUSIONS: We developed a structured scholarly productive model workshop for healthcare staff working at hospitals. We found healthcare staff with clinical subspecialties were able to develop an unexpectedly high number of research questions through this workshop. Medical teachers at hospitals with prior systematic review experience could teach how to develop systematic review protocols using this model. Further research is needed to increase the academic productivity of such workshops. TRIAL REGISTRATION: UMIN (https://www.umin.ac.jp/ctr/), UMIN000017107 (4/15/2015), UMIN000025580 (1/10/2017).

Effect of prostaglandin F2α administration on uterine polymorphonuclear neutrophil counts in Japanese heavy draft horses.

The objective of this study was to examine the effect of prostaglandin F2α (dinoprost) and oxytocin administration on uterine polymorphonuclear neutrophil counts in the Japanese heavy draft mare. To compare polymorphonuclear neutrophil (PMN) counts in the endometrium, a total of 162 samples were collected from 54 estruses of 47 mares (before ovulation, day 0, and day 2) using a double-guarded cytology brush. Dinoprost (PG; 5 mg) was administered intramuscularly (i.m.) only once, on day 0, whereas oxytocin (OT; 20 U i.m.) was administered three times at 12-hr intervals starting on day 0. The plasma progesterone concentrations from days 0 to 14 were not different between the non-treatment (CON), PG treatment, and OT treatment groups. The PMN counts increased in all the groups from before administration to day 0 (CON, 0.90 to 3.55; PG, 1.20 to 8.45; and OT, 0.70 to 1.70; P=0.0014, 0.0046, and 0.0073, respectively). There was a significant decrease in PMNs from day 0 to day 2 only in the PG group (P=0.0073). The pregnancy rate was not different among the CON (12/18), PG (14/18), and OT (10/18) groups. The results of this study indicate that dinoprost can reduce uterine polymorphonuclear neutrophil counts.

Correction to: Voice rehabilitation for laryngeal cancer after radiotherapy: a systematic review and meta-analysis.

In the original publication of the article, the reference 14 was published incorrectly. The correct reference is given below.

Videolaryngoscopy for transesophageal echocardiography probe insertion: a systematic review and meta-analysis of randomized controlled trials.

Transesophageal echocardiography (TEE) is a well-established procedure, but serious complications may occur. This systematic review and meta-analysis assessed the utility of videolaryngoscopy-assisted technique in TEE probe insertion. We performed a systematic search in MEDLINE, EMBASE, CENTRAL, and ICTRP. We included RCTs comparing TEE probe insertion techniques assisted with videolaryngoscopy and with any other insertion technique in adult patients. Primary outcome measures were (1) the number of attempts before successful TEE probe insertion, and (2) the risk of any procedural injury to related structures. The secondary outcome measure was time to TEE probe insertion. In total, three studies (n = 266) were included in this systematic review. Overall, a significantly less number of attempts were required with videolaryngoscopy-assisted insertion (mean difference [MD] - 0.60; 95% confidence interval [CI] - 0.73, - 0.46; low quality of evidence). Videolaryngoscopy-assisted technique was also associated with smaller risk of complications (risk ratio [RR] 0.17; 95% CI 0.05, 0.62; low quality of evidence). There was no significant difference in time to probe insertion (MD - 8.57; 95% CI - 26.31, 9.16; very low quality of evidence). The use of videolaryngoscopy for TEE probe insertion is associated with a significant reduction in the number of attempts and complication rate.

Voice rehabilitation for laryngeal cancer after radiotherapy: a systematic review and meta-analysis.

PURPOSE: We aimed to determine whether voice rehabilitation after radiotherapy improves the quality of life (QOL), voice function, and self-rated voice function in patients with laryngeal cancer. METHODS: We searched CENTRAL, MEDLINE, EMBASE, PEDro, and World Health Organization International Clinical Trials Registry Platform for randomized controlled trials published between inception and October 2018. The primary outcome was QOL, adverse events and mortality. Secondary outcomes included voice function and self-rated voice function. The quality of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Three trials (enrolling 122 patients) compared voice rehabilitation to usual care or no intervention after radiotherapy. Voice rehabilitation did not significantly improve any QOL scores. Data on adverse events and mortality were not available in any of the trials. Voice rehabilitation did not improve any voice function scores, such as jitter (mean difference: - 0.48 [- 1.27 to 0.32]), shimmer (mean difference: - 0.04 [- 0.27 to 0.19]), maximum phonation time (mean difference: 1.54 [- 1.13 to 4.22]), and the grade, roughness, breathiness, asthenia, and strain scale (mean difference: - 0.39 [- 2.59 to 1.80]). Voice rehabilitation also did not improve the voice handicap index, which was used as a self-rated voice function score (mean difference: 5.54 [- 2.07 to 13.16]). The certainty of the evidence was graded as low for primary and secondary outcomes. CONCLUSION: Voice rehabilitation for patients with laryngeal cancer after radiotherapy might not improve QOL, voice function, and self-rated voice function. Pre-specified voice rehabilitation programs may not be necessary for all patients with laryngeal cancer after radiotherapy.