The diagnostic ability of SPECT/CT fusion imaging for gastrointestinal bleeding: a retrospective study.

BACKGROUND: Blood loss from the gastrointestinal tract can be an acute and life-threatening event. For the treatment of gastrointestinal bleeding, it is important to accurately detect gastrointestinal bleeding and to localize the sites of bleeding. The purpose of this study was to retrospectively assess the capabilities of SPECT/CT in the diagnosis of gastrointestinal bleeding by a comparison with planar imaging alone as well as planar and SPECT. METHODS: We conducted a retrospective analysis of 20 patients (21 examinations) who underwent gastrointestinal bleeding scintigraphy in the past 7 years and in whom the bleeding site was identified by endoscopy or capsule endoscopy, or in whom no evidence of gastrointestinal bleeding was identified during the clinical course. Five patients (5 examinations) were diagnosed by planar imaging (planar group). Eight patients (9 examinations) were diagnosed by planar imaging and SPECT (planar + SPECT group). Seven patients (7 examinations) were diagnosed by planar imaging and SPECT/CT (planar + SPECT/CT group). We calculated the diagnostic ability of each method in detecting the presence of bleeding, as well as the ability of each method to identify the sites of bleeding. The sensitivity, specificity, and accuracy of the methods were compared. RESULTS: The diagnostic ability of the three imaging methods in detecting the presence of gastrointestinal bleeding was as follows. Planar imaging showed 100% sensitivity (3/3), 100% specificity (2/2), and 100% accuracy (5/5). Planar + SPECT imaging showed 85.7% sensitivity (6/7), 100% specificity (2/2), and 88.9% accuracy (8/9). Planar + SPECT/CT imaging showed 100% sensitivity (6/6), 100% specificity (1/1), and 100% accuracy (7/7). The diagnostic ability of the three modalities in detecting the site of bleeding was as follows: planar, 33.3% (1/3); planar + SPECT, 71.4% (5/7); and planar + SPECT/CT, 100% (6/6). CONCLUSIONS: All 3 imaging methods showed good accuracy in detecting the presence of gastrointestinal bleeding. The addition of SPECT or SPECT/CT made the anatomical position of the uptake clear and contributed to the localization of the site of gastrointestinal bleeding. Planar + SPECT/CT imaging therefore showed the highest diagnostic ability for detecting the site of gastrointestinal bleeding.

Treatment using tadalafil for severe pre-eclampsia with fetal growth restriction.

For severe pre-eclampsia (PE) with fetal growth restriction (FGR), the only effective treatment is early delivery of the placenta. Clinicians are often forced to end the pregnancy because of maternal indications. We report a case of severe PE with FGR in which the PE was temporarily improved and pregnancy successfully prolonged with tadalafil, a phosphodiesterase 5 inhibitor. A 35-year-old primigravid woman presented at 27 3/7 weeks of gestation with severe PE and FGR. After commencing tadalafil administration, biochemical and angiogenic markers improved. Thereafter, hypertension and proteinuria temporarily improved. Importantly, the pregnancy was prolonged by 14 days after the initiation of tadalafil administration. Tadalafil may be a novel treatment for severe PE with FGR to prolong pregnancy.

Comparing Papanicolaou test results obtained during pregnancy and post-partum.

AIM: Cervical cancer onset initially occurs during youth. Papanicolaou tests performed in early pregnancy can detect cervical cancer; however, Papanicolaou tests during pregnancy have been noted to be inaccurate, reflecting changes associated with pregnancy. Therefore, we assessed the effect of pregnancy on Papanicolaou test results. METHODS: Of 1351 pregnant women who delivered at Ise Red Cross Hospital between January 2010 and December 2014, 1213 underwent Papanicolaou tests at early pregnancy and post-partum. We compared the Papanicolaou test results. RESULTS: The results of the Papanicolaou test were different in 32 patients. Of the 1191 patients negative for intraepithelial lesions or malignancy in early pregnancy, 16 had other cytological abnormalities post-partum. We performed therapeutic conization post-partum in four patients. The Papanicolaou test results in early pregnancy of the four patients were negative for intraepithelial lesions or malignancy in one patient, atypical squamous cells of undetermined significance in one and high-grade squamous intraepithelial lesion in two. CONCLUSION: The results of the Papanicolaou test during pregnancy may not be accurate because of the influence of hormones associated with pregnancy. Taking advantage of the one-month post-partum screening visit can lead to early detection and treatment of cervical cancer in young people.

Retrospective study of tadalafil for fetal growth restriction: Impact on maternal and perinatal outcomes.

AIM: The aim of this retrospective study was to assess tadalafil treatment in pregnant women with fetal growth restriction (FGR) in terms of maternal and perinatal outcomes. METHODS: We retrospectively analyzed 11 Japanese singleton pregnant women with FGR who received tadalafil along with conventional management for FGR at Mie University Hospital from July 2015 to February 2016 (tadalafil group). These women were matched for maternal age, parity, gestational age, and estimated fetal weight at enrollment with 14 singleton pregnant women who received only the conventional management for FGR in 2014 (conventional management group). The conventional management for FGR was performed according to guidelines for obstetric practice in Japan. RESULTS: Both birthweight and fetal growth velocity from enrollment to birth were significantly higher in the tadalafil group than in the conventional management group. The cesarean delivery rate was approximately twofold higher in the conventional management group than in the tadalafil group. Importantly, cesarean section due to non-reassuring fetal status was performed in seven pregnant women in the conventional management group (58.3%) but in none in the tadalafil group (P < 0.05, chi-squared test). CONCLUSIONS: Tadalafil may improve perinatal outcome in FGR by modulating fetal growth through maintenance or improvement of fetal well-being.

Safety and dose-finding trial of tadalafil administered for fetal growth restriction: A phase-1 clinical study.

AIM: We designed a safety and dose-finding trial of tadalafil administered for fetal growth restriction (FGR). METHODS: Three cases were initially commenced on 10 mg/day and monitored for major adverse events. Should a major adverse event be observed in one or more of the three cases, an examination into its relation with tadalafil would be conducted by a safety evaluation committee. If one or more of these new cases exhibited the same adverse event, the trial would be stopped completely. If there were no harmful side-effects, the trial would be extended to three cases at 20 mg/day, and the protocol would continue as in the 10-mg/day dose. The 40-mg/day dosage was tried in six cases as the dosage was considered to be high. RESULTS: The study population consisted of pregnant women with FGR. Maternal adverse events in all doses were recorded as least one grade 1 adverse events, as tadalafil was considered acceptable from the viewpoint of the mothers. However, a dose of 40 mg/day increased the number of grade 1 adverse events. The only fetal adverse event was a case of intrauterine fetal death related to the velamentous insertion of the umbilical cord. Neonatal adverse events showed no correlation to tadalafil dose, but were found more frequently in preterm births and, therefore, were correlated to infant prematurity. CONCLUSION: This safety and dose-finding trial showed that tadalafil had a favorable safety profile for pregnant women and fetuses with FGR.

Axillary Lymph Node Uptake on 18F-FDG PET/CT after COVID-19 Vaccination: A Direct Comparison Study with Influenza Vaccination.

Objectives: To compare vaccinated-side axillary lymph node uptake on 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) after coronavirus disease-2019 (COVID-19) and influenza vaccination. Methods: We retrospectively analyzed 177 patients who underwent 18F-FDG PET/CT after COVID-19 or influenza vaccination. We compared the uptake of the vaccinated-side axillary lymph nodes of 109 COVID-19 vaccinated patients with those of a lot of influenza-vaccinated patients. We also compared the uptake between 66 patients who received the first COVID-19 vaccination with 43 who received the second COVID-19 vaccination. Results: 18F-FDG-avid axillary lymph nodes on the vaccinated side were significantly more frequently observed in the COVID-19 group (45%) than in the influenza group (19%) (p<0.001). When the interval between vaccination to PET/CT was within 7 days, there was no significant difference in the frequency of 18F-FDG-avid vaccinated-side axillary lymph nodes between the groups (COVID-19 group: 41% vs. influenza group: 45%, p=0.724). When the interval was over 7 days, 18F-FDG-avid lymph nodes were much more frequent in the COVID-19 group (47%) than in the influenza group (7%) (p<0.001). Comparing the first and second COVID-19 groups, 18F-FDG-avid lymph nodes were more frequent in the second vaccination group than in the first vaccination group, but the difference was not significant. Conclusion: 18F-FDG-avid vaccinated-side axillary lymph nodes were more frequently observed in the COVID-19 group than in the influenza group. In the case of the COVID-19 vaccine, a delay of 18F-FDG PET/CT examination is recommended by a longer interval from vaccination than in the influenza vaccine.

Increased physiological [18F]FDG uptake in the liver and blood pool among patients with impaired renal function.

BACKGROUND: In the daily clinical course, the liver uptake may seem to be increased in patients with renal failure. The purpose of this study was to investigate whether or not the FDG uptake of the liver, and the FDG uptake of blood pool which is generally used as a reference site as well as liver, is increased in patients with renal failure. MATERIAL AND METHODS: We retrospectively analyzed 233 patients who underwent FDG positron emission tomography/computed tomography (PET/CT). Renal failure is defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. We compared the FDG uptake in the liver and mediastinal blood pool of 67 patients with impaired renal function to that in 166 patients with a normal renal function (eGFR ≥ 60 mL/min/1.73 m2). Correlations between the liver or mediastinal blood pool FDG uptake and the eGFR were also analyzed by Spearman's correlation test. RESULTS: Maximum and mean standardized uptake values (SUVmax and SUVmean, respectively) of the liver and the SUVmean of the mediastinal blood pool were 3.48 ± 0.57, 2.56 ± 0.37, and 1.90 ± 0.28 in the impaired renal function group, respectively, and 3.13 ± 0.45, 2.29 ± 0.33, and 1.66 ± 0.23, in the normal group, respectively. The SUVmax and SUVmean of the liver and SUVmean of the mediastinal blood pool in the impaired renal function group were significantly higher than those in the normal group (p < 0.001, < 0.001, and < 0.001, respectively). The SUVmax and SUVmean of the liver and SUVmean of the mediastinal blood pool of patients showed a significant negative correlation with the eGFR (Spearman's p = -0.25, -0.30, and -0.40, respectively, each p < 0.001). CONCLUSIONS: FDG uptake in both the liver and mediastinal blood pool was higher in patients with impaired renal function.

Clinical application of dynamic 18F-fluorodeoxyglucose positron-emission tomography / computed tomography in the differential diagnoses of musculoskeletal lesions.

We aimed to assess the differential diagnostic efficacy of dynamic F-18 fluorodeoxyglucose (FDG) positron emission tomography / computed tomography (PET / CT) and to evaluate the appropriate scan timings for diagnosis of musculoskeletal lesions (MSLs). Dynamic scans (5-15 [phase 1], 15-25 [phase 2], and 25-35 [phase 3] min after F-18 FDG injection) and dual-time-point scans (1 and 2 h after injection) were acquired for 23 MSLs [4 benign MSLs (BMSLs). 10 primary malignant musculoskeletal tumors (PMMSTs), and 9 metastatic musculoskeletal tumors (MMSTs)]. We compared the maximum standardized uptake values (SUVmax) and corresponding retention indices for dynamic (RI-SUVdyn) and dual-time-point (RI-SUVdual) scans and evaluated diagnostic efficacy using receiver operating characteristic (ROC) curve analyses. The SUVmax gradually decreased or was almost identical with minimal fluctuation in 3 BMSLs and 1 PMMST. SUVmax increased over time after phase 2 in 18 malignant MSLs (MMSLs). There were significant differences in SUVmax (for all time phases) and RI-SUV dual between BMSLs and MMSLs and between PMMSTs and MMSTs. In the ROC analyses, the areas under the curve for SUV in phases 2 and 3 were highest for differentiating BMSLs from MMSLs and PMMSTs from MMSTs, respectively. Dynamic F-18 FDG PET / CT is valuable for diagnosis of musculoskeletal lesions. J. Med. Invest. 68 : 96-104, February, 2021.

Phase-1 clinical study of tadalafil administered for selective fetal growth restriction in twin pregnancy.

BACKGROUND: Selective fetal growth restriction (sFGR) is a condition of twin pregnancy in which the development of one fetus is restricted, despite normal growth of the other fetus. A method of intrauterine therapy for sFGR does not currently exist. The only treatment for sFGR is to terminate the pregnancy before the FGR worsens. In twin pregnancies, maternal and intrauterine environments are common in both fetuses, thus a placental factor is considered the cause of FGR in fetuses. Tadalafil is a phosphodiesterase (PDE)-5 inhibitor that induces an increase in uterine blood flow by dilatation of blood vessels in cases of FGR with placental dysfunction, which improves FGR. PURPOSE: The aim of this study was to investigate the safety and maximum tolerated dose (MTD) of tadalafil administered for twin pregnancy (diamniotic-monochorionic twin or diamniotic-dichorionic twin). METHODS: In this phase I, open-label, dose-escalation trial, sequential patient cohorts (3 + 3 dose-escalation design) for twin pregnancy received tadalafil (20 or 40 mg/d) as a single dose by oral administration from the day they were diagnosed with sFGR, defined as estimated fetal weight (EFW) < 3% tiles, that is, -1.8 SD the mean EFW for gestational age (GA) to unacceptable toxicity or the day of delivery. This study evaluated the safety of maternally administered tadalafil for sFGR, examining maternal, fetal, and neonatal adverse events. Maternal adverse events were graded on the basis of the Common Terminology Criteria for Adverse Events v4.0. RESULTS: Six women with sFGR who were pregnant with twins were treated with tadalafil. There were no severe adverse events in either cohort, although the most common (≥3 patients) drug-related adverse events were headache and heart failure. The MTD of tadalafil among Japanese patients was 40 mg. CONCLUSIONS: Tadalafil has a manageable safety profile up to an MTD of 40 mg/d.

Preliminary clinical assessment of dynamic carbon-11 methionine positron-emission tomography/computed tomography for the diagnosis of the pathologies in patients with musculoskeletal lesions: a prospective study.

BACKGROUND: This study prospectively assessed the diagnostic capacity of dynamic carbon-11 methionine (C-11 MET) positron-emission tomography (PET)/computed tomography for the diagnosis of pathologies in patients with primary unknown musculoskeletal lesions (MSLs). In total, 13 patients with MSLs underwent dynamic scans (5-10 [phase 1], 10-15 [phase 2], 15-20 [phase 3], 20-25 [phase 4], 25-30 [phase 5], and 30-35 [phase 6] min post-injection of C-11 MET). We statistically compared the maximum standardised uptake values (SUVmax) and corresponding retention index for dynamic scans (RI-SUV) for five benign MSLs (BMSLs), five primary malignant musculoskeletal tumours (PMMSTs), four metastatic musculoskeletal tumours (MMSTs), and three malignant lymphoma (ML) cases and explored their diagnostic capacities using receiver operating characteristic (ROC) curve analyses. RESULTS: SUVmax gradually decreased or remained similar with minimal fluctuations in all BMSL cases and four of five PMMST cases. In contrast, SUVmax increased over time in one case of PMMST and in all cases of MMST and ML. Significant differences were observed in SUVmax for all time phases and RI-SUV between BMSLs and MMSLs, in SUVmax for all time phases between PMMSTs and BMSLs, in SUVmax for all time phases and RI-SUV between non-PMMST-malignant tumours and BMSL, and in RI-SUV between non-PMMST-malignant tumours and PMMST. In ROC analyses, the areas under the curve yielded the highest values at 1.00 for differentiating most intergroup comparisons. CONCLUSIONS: Dynamic C-11 MET PET scans have the potential to be good predictors of discriminating MSLs in patients with primary unknown MSLs in clinical practice.

Preliminary clinical assessment of dynamic 18F-fluorodeoxyglucose positron-emission tomography/computed tomography for evaluating the clinicopathological grade in patients with non-Hodgkin's lymphoma: a prospective study.

OBJECTIVE: We prospectively assessed the diagnostic capacity of dynamic and dual-time-point F-fluorodeoxyglucose PET/computed tomography and explored the most appropriate scan timing for clinicopathological discrimination of non-Hodgkin's lymphoma. METHODS: Thirteen patients underwent dynamic scans dynamic scans (5-15, 15-25, and 25-35 minute postinjection) and consecutive dual-time-point scans (1- and 2-hour postinjection). For five indolent and 16 aggressive lymphomas, we statistically compared the maximum standardized uptake value (SUVmax) and the retention index of the SUVmax (RI-SUVmax) for each scan and explored the diagnostic capacities using receiver operating characteristic (ROC) curve analyses. RESULTS: SUVmax increased progressively over time in all lymphomas and was significantly higher for aggressive lymphoma than for indolent lymphoma in each timephase. RI-SUVmax of dynamic scans (RI-SUV-dynamic) was significantly higher in aggressive than in indolent lymphoma. The cutoff values obtained a sensitivity of 94%, positive-predictive value of 94%, and accuracy of 91% for SUVmax analyses of the dynamic second and third phases, 1-hour early phase, and 2-hour delayed phase, and a sensitivity of 88%, positive-predictive value of 93%, and accuracy of 86% for RI-SUV-dynamic. In contrast, for the dynamic first phase, the cutoff value of SUVmax yielded moderate sensitivity of 69%, a positive-predictive value of 92%, and an accuracy of 71%. The area under the ROC curve (AUC) of the RI-SUV-dynamic had the highest value (0.938), whereas the AUCs of the other ROC analyses were not significantly different. CONCLUSION: The dynamic second and third phase could potentially provide good predictors of clinicopathological discrimination, as can the early and delayed phases.

Semiquantitative assessment of fluorodeoxyglucose uptake in primary tumours on dynamic PET/computed tomography for lymph node metastasis evaluation in patients with lung cancer: a prospective study.

OBJECTIVE: To semiquantitatively estimate fluorine-18-fluorodeoxyglucose (FDG) uptake in primary lung cancer cells using dynamic and dual-time-point (DTP) PET/computed tomography (PET/CT) to obtain a diagnostic index for lymph node metastasis. METHODS: Forty-five patients with lung cancer underwent dynamic and DTP PET/CT examinations. All primary lesions and lymph node metastases were evaluated pathologically. At each time phase, we assessed the maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of the primary tumours. We investigated the relationship between semiquantitative index and the presence of lymph node metastasis for each case and for all cases satisfying indications for segmentectomy. In cases with lymph node metastasis, we assessed the SUVmax of pathologically proven metastatic lymph nodes and nonmetastatic lymph nodes in each dynamic phase for evaluating temporal change. RESULTS: Among 45 patients, 15 had 17 lymph node metastasis. SUVmax, MTV and TLG of primary tumours at each time phase were significantly associated with lymph node metastasis (P < 0.05). In receiver operating characteristic analysis, dynamic second and third phases showed high diagnostic ability for lymph node metastasis. The temporal change in SUVmax in the dynamic phase between primary tumours and metastatic lymph nodes were significantly different (P = 0.065). The temporal change in SUVmax was significantly lower in nonmetastatic lymph nodes than in primary tumours and metastatic lymph nodes (P < 0.0001). CONCLUSIONS: Semiquantitative assessment of FDG uptake in dynamic second and third phases and the assessment of temporal changes in SUVmax on dynamic PET/CT scans were important predictors in diagnosing lymph node metastasis.

Preliminary clinical assessment of dynamic 18F-fluorodeoxyglucose positron emission tomography/computed tomography for evaluating lymph node metastasis in patients with lung cancer: a prospective study.

OBJECTIVE: We assessed the diagnostic capacity of dynamic fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and dual-time-point (DTP) PET/CT to explore the optimal scan timing for nodal staging in lung cancer. METHODS: Thirty-four patients with lung cancer underwent dynamic and consecutive DTP PET/CT scans. Two readers visually evaluated FDG uptake within each lymph node (LN) and pulmonary artery (metastatic LN: n = 10; nonmetastatic LN: n = 121). For each dynamic and DTP scan, we compared the maximum standardized uptake value (SUVmax) and the retention index of the SUVmax (RI-SUVmax) between metastatic and nonmetastatic LNs. We compared the diagnostic capacity of the dynamic and DTP scans using receiver operating characteristic (ROC) analyses. RESULTS: In the visual analyses of LN metastases, a sensitivity of 20.0-60.0% and specificity of 97.5-100.0% were identified for the first to third dynamic scans. The sensitivity of the 1-h early and 2-h delayed scans was 80.0% and 90.0%, respectively, whereas the specificity was 66.9% and 47.9%, respectively. The visual analysis of the dynamic second phase had the highest accuracy. Semiquantitative analyses revealed that the SUVmax was significantly higher for metastatic LNs than for nonmetastatic LNs in the dynamic second and third phases and the 1-h early and 2-h delayed phases (p < 0.05 for all). The RI-SUVmax was higher in metastatic LNs than in nonmetastatic LNs for the dynamic scan (p = 0.004) and the DTP scan (p = 0.002). The ROC analyses showed that SUV2 and SUV3 had higher performances with high specificity, high negative predictive value, and high accuracy than the other parameters. The area under the ROC curve of the RI-SUV-dual-time-point had the highest value (0.794) without any significant differences between the area under the ROC curves for all parameters (p > 0.05 for all). CONCLUSIONS: Based on the visual and semiquantitative analyses, 18F-FDG dynamic PET/CT exhibited excellent performance with extremely high specificity in the dynamic second phase.

Cardiac function and tadalafil used for treating fetal growth restriction in pregnant women without cardiovascular disease.

BACKGROUND: The aim of the present study was to evaluate tadalafil for the treatment of fetal growth restriction (FGR) and the cardiac function in pregnant women without cardiovascular disease who used tadalafil for this reason. MATERIALS AND METHODS: We examined nine pregnant women without cardiovascular disease who were using tadalafil to treat FGR. Maternal heart rate, systolic blood pressure (BP), and echocardiographic findings were assessed before and after tadalafil use. RESULTS: Diastolic BP was lower after compared to that before using tadalafil, but the difference was not significant. Echocardiographic findings were not significantly different before and after tadalafil use. CONCLUSIONS: Tadalafil did not adversely affect pregnant women without cardiovascular disease and was considered acceptable for use since it did not affect the mother's cardiac function.

Safety and Efficacy of Laparoscopic Oophorocystectomy for Ovarian Dermoid Cyst Associated With Autoimmune Hemolytic Anemia.

Ovarian dermoid cysts (ODCs) are the most common benign tumors in young women, but autoimmune hemolytic anemia (AIHA) induced by ODC is rare. We report the first case of ODC-associated AIHA with improvement after laparoscopic oophorocystectomy. An 18-year-old nulliparous woman was diagnosed with a left ODC that was 7 cm in diameter. Preoperative blood tests showed macrocytic anemia, reticulocytosis, high serum lactate dehydrogenase activity, hyperbilirubinemia, and low haptoglobin. Direct and indirect Coombs tests were positive. We diagnosed AIHA. Prednisolone therapy did not result in improvement, so it seemed that AIHA was being induced by the ODC. After laparoscopic oophorocystectomy, the patient's condition improved without blood transfusion. Resection of ODC should be performed first for ODC-associated AIHA; laparoscopic surgery may be superior to laparotomy from the standpoint of hemorrhage given the underlying anemia.

Clinical factors associated with in-hospital death in pediatric surgical patients admitted to the neonatal intensive care unit: a 15-year single tertiary center experience.

BACKGROUND/PURPOSE: The purpose of this study was to explore clinical characteristics and primary surgical diagnoses associated with in-hospital death in pediatric surgical patients admitted to the neonatal intensive care unit (NICU) of a tertiary hospital. METHODS: This retrospective study includes all patients admitted to our NICU for pediatric surgical diseases between January 2001 and December 2015. Univariate and multivariate binary logistic regression were performed to assess independent factors associated with in-hospital death. RESULTS: A total of 440 cases were included and 334 (83.5%) patients underwent one or more surgeries. Thirty six patients (8.2%) died while hospitalized in the NICU. The 5 most common surgical diagnoses were intestinal atresia/stenosis, anorectal malformation, congenital diaphragmatic hernia (CDH), esophageal atresia, and urinary system disorder. Necrotizing enterocolitis (NEC) had the highest mortality rate. Using logistic regression, in-hospital death was predicted by extremely low birth weight (ELBW) (odds ratio (OR)=6.594; P=0.006), CDH (OR=13.954; P<0.001), and NEC (OR=8.991; P=0.049). CONCLUSIONS: This study describes CDH, NEC, and ELBW are independent predictive factors associated with in-hospital death of pediatric surgical patients in our NICU. Novel approaches for those conditions are required to improve the survival. TYPE OF STUDY: Prognostic LEVELS OF EVIDENCE: II.

TADAFER II: Tadalafil treatment for fetal growth restriction - a study protocol for a multicenter randomised controlled phase II trial.

INTRODUCTION: There is no proven therapy to reverse or ameliorate fetal growth restriction (FGR). Sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, has been reported to potentially play a therapeutic role in FGR, but this has not been established. Tadalafil is also a selective PDE5 inhibitor. We have demonstrated the efficacy of tadalafil against FGR along with short-term outcomes and the feasibility of tadalafil treatment. Based on the hypothesis that tadalafil will safely increase the likelihood of increased fetal growth in FGR, we designed this phase II study to prospectively evaluate the efficacy and safety of tadalafil against FGR. METHODS AND ANALYSIS: This study is a multicentre, randomised controlled phase II trial. A total of 140 fetuses with FGR will be enrolled from medical centres in Japan. Fetuses will be randomised to receive either the conventional management for FGR or a once-daily treatment with 20 mg of tadalafil along with the conventional management until delivery. The primary endpoint is fetal growth velocity from the first day of the protocol-defined treatment to birth (g/day). To minimise bias in terms of fetal baseline conditions and timing of delivery, a fetal indication for delivery was established in this study. The investigator will evaluate fetal baseline conditions at enrolment and will decide the timing of delivery based on this fetal indication. Infants will be followed up for development until 1.5 years of age. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of Mie University Hospital and each participating institution. Our findings will be widely disseminated through peer-reviewed publications. TRIAL REGISTRATION NUMBER: UMIN000023778.

Novel fission yeast Cdc7-Dbf4-like kinase complex required for the initiation and progression of meiotic second division.

Cdc7, a conserved serine/threonine protein kinase, controls initiation of DNA replication. A regulatory subunit, Dbf4, stimulates the kinase activity of Cdc7 and recruits it to the replication origins. Schizosaccharomyces pombe has a homologous kinase complex, composed of Hsk1 and Dfp1/Him1. Here, we report a novel protein kinase of S. pombe, Spo4, which shares common structural features with the Cdc7 kinases. In spite of the structural similarities, Spo4 is dispensable for mitotic growth and premeiotic DNA replication. Intriguingly, spo4 null mutants are defective in initiation and progression of the second meiotic division. Spindles for meiosis II are often fragmented. Spo4 kinase activity is markedly enhanced when the enzyme is associated with its regulatory subunit, Spo6, a Dbf4-like protein. Expression of Spo4 is specifically induced during meiosis. Spo4 is preferentially present in nuclei, but this nuclear localization does not require Spo6. These results suggest that Spo4 is a Cdc7 kinase whose primary role is in meiosis, not in DNA replication. This is the first report of an organism which has two Cdc7-related kinase complexes with different biological functions.

The fission yeast spo14+ gene encoding a functional homologue of budding yeast Sec12 is required for the development of forespore membranes.

The Schizosaccharomyces pombe spo14-B221 mutant was originally isolated as a sporulation-deficient mutant. However, the spo14(+) gene is essential for cell viability and growth. spo14(+) is identical to the previously characterized stl1(+) gene encoding a putative homologue of Saccharomyces cerevisiae Sec12, which is essential for protein transport from the endoplasmic reticulum (ER) to the Golgi apparatus. In the spo14 mutant cells, ER-like membranes were accumulated beneath the plasma membrane and the ER/Golgi shuttling protein Rer1 remained in the ER. Sec12 is a guanine nucleotide exchange factor for the Sar1 GTPase. Overproduction of psr1(+) coding for an S. pombe Sar1 homologue suppressed both the sporulation defect of spo14-B221 and cold-sensitive growth of newly isolated spo14-6 and spo14-7 mutants. These results indicate that Spo14 is involved in early steps of the protein secretory pathway. The spo14-B221 allele carries a single nucleotide change in the branch point consensus of the fifth intron, which reduces the abundance of the spo14 mRNA. During meiosis II, the forespore membrane was initiated near spindle pole bodies; however, subsequent extension of the membrane was arrested before its closure into a sac. We conclude that Spo14 is responsible for the assembly of the forespore membrane by supplying membrane vesicles.

The physiological accumulation of FDG in the muscles in relation to the side of intravenous administration.

PURPOSE: The purpose of the study was to evaluate the physiological accumulation of 18F-FDG in the muscles in relation to the side of intravenous administration. MATERIALS AND METHODS: We retrospectively investigated 3,118 18F-FDG-PET/CT examinations. We evaluated the physiological accumulation of FDG in the muscles of the shoulder and arm relative to its dependence on the side of intravenous administration. RESULTS: Six hundred six of the 3,118 examinations (19.4%) showed physiological accumulation of FDG in the teres minor muscle. Accumulation was seen on the side of administration in 486 examinations (80.2%), contralateral to the side of administration in 56 examinations (9.2%), and bilaterally in 64 examinations (10.6%). Five hundred seventy-seven of the 3,118 examinations (18.5%) showed accumulation of FDG in the muscles between the radioulna near the elbow. Accumulation was observed on the side of administration in 432 examinations (74.9%), contralateral to the side of the administration in 71 examinations (12.3%), and bilaterally in 74 examinations (12.8%). CONCLUSION: The present study finds that not only accumulation in the teres minor muscles but also accumulation in the muscles between the radioulna near the elbow occurs significantly more frequently on the side of intravenous administration compared to the contralateral side.