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Preeclampsia and eclampsia is a complication in the labor process whose incidence is always high. The purpose of this study was to study the relationship between Birth Weight and the incidence of preeclampsia in RSUD dr. M. Yunus, Bengkulu city in 2017. The type of research used in this study is Survey Analytic using the Cross Sectional method. The population in this study was overall in the hospital of Dr. M. Yunus City of Bengkulu in January to December in 2017 which is 362 babies. The sampling technique in this study was 78 proportional sampling. The data used is secondary data obtained from the patient register at Dr. M Yunus Hospital in Bengkulu. Data were analyzed using univariate and bivariate analysis with Chi-Square test (2) and Contingency Coefficient (C) test. The results obtained: Of the 78 newborns sampled there were 60 infants (76.9%) normal birth weight, 55 people (70.5%) did not experience preeclampsia, there was a significant relationship between preeclampsia and low infant weight in RSUD dr. M. Yunus Bengkulu in the tight category. It is expected that health workers can maintain and improve the quality of their abilities and skills to deal with babies with low birth weight born by preeclampsia patients or other patients.

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

Background: Patients with life-limiting illnesses frequently experience urinary difficulties, and urinary catheterization is one of the interventions for managing them. However, evidence supporting the effects of urinary catheters on the quality of death (QoD) is lacking in this population. Objectives: To investigate whether urinary catheterization affects QoD in patients with advanced cancer in palliative care units. Design: A secondary analysis of a multicenter, prospective cohort study. Setting/Subjects: The study enrolled consecutive patients with advanced cancer admitted to palliative care units in Japan between January and December 2017. Those who were not catheterized on admission and who died while in a palliative care unit were analyzed. Measurements: QoD was evaluated at death using the Good Death Scale (GDS). Results: Of 885 patients, 297 (33.6%) were catheterized during their palliative care unit stay. Females and patients with a long palliative care unit stay were more likely to be catheterized. In inverse probability-weighted propensity score analysis, patients with urinary catheterization during their palliative care unit stay had higher total GDS scores than those without catheterization (coefficient 0.410, 95% confidence interval 0.068-0.752). In subgroup analyses stratified by sex, age, and length of palliative care unit stay, urinary catheterization was associated with higher total GDS scores in patients younger than 65 years of age and those who died after a palliative care unit stay of 21 days or fewer. Conclusions: This study suggested that urinary catheterization during a palliative care unit stay may have a positive impact on overall QoD in patients with advanced cancer. This study was registered in the UMIN Clinical Trials Registry (UMIN000025457).

Due to treatment associated risks, it is still debatable which unruptured aneurysm should be treated. Anatomic and morphologic characteristics may aid to predict the rupture risk of superior cerebellar artery (SCA) aneurysm and possibly support in decision- making during treatment.To identify morphologic characteristics that could predict the rupture of SCA aneurysms.A retrospective analysis of computed tomography angiography images of 81 consecutive patients harboring SCA aneurysm who were treated between 1980 to 2014 at Helsinki University Hospital was performed.Of the 81 analyzed SCA aneurysms, 30 (37%) were unruptured and remaining 51 (63%) presented with subarachnoid hemorrhage. The mean ± SD size of unruptured SCA aneurysms was 6.2 ± 6.3 mm; mean size of ruptured SCA aneurysms was 5.9 ± 5.4 mm. The mean ± SD aspect ratio was 0.9 ± 0.3 in unruptured and 1.14 ± 0.44 in ruptured SCA aneurysms. The mean ± SD degree angle between basilar artery and aneurysm was 74.7 ± 24.4 in unruptured and 65.9 ± 23 ruptured SCA aneurysms. Patients with ruptured SCA aneurysm showed significantly higher aspect ratio (Mann-Whitney U, P = 0.01) and smaller aneurysm to basilar artery angle (Mann-Whitney U, P = 0.039). Aspect ratio1.1 had 2.3 times higher risk of rupture (odds ration [OR] 2.3, 95% confidence interval [CI] 0.84-6.34). An aneurysm to basilar angle70 degrees had 2.8 times higher risk of rupture (OR 2.75, 95% CI 1.086-6.96).Ruptured SCA aneurysms are usually small in size. Higher aspect ratio and smaller angle between SCA aneurysm and basilar artery had significantly higher risk of SCA (S1 segment) aneurysm rupture.

Background: Dental phobia is covered by medical insurance; however, the diagnostic methods are not standardized in Japan. Therefore, the aim of this study was to investigate the methods and use of questionnaires for the diagnosis of dental phobia by Japanese dental practitioners specializing in special needs dentistry and dental anesthesiology. Methods: We conducted an online survey to obtain information from the members of the Japanese Society for Disability and Oral Health (JSDH, n = 5134) and the Japanese Dental Society of Anesthesiology (JDSA, n = 2759). Response items included gender, qualification, affiliation type, methods of diagnosis and management of dental phobia, use of questionnaire, need to establish standardized diagnostic method for dental phobia, and others. The chi-squared test was used to compare answers between the three groups: JSDH only, JDSA only, and both JSDH and JDSA. Multiple logistic regression analysis was conducted to identify factors associated with the use of an assessment questionnaire. Results: Data were obtained from 614 practitioners (JSDH only, n = 329; JDSA only, n = 195; both JSDH and JDSA: n = 90, response rate: 7.8% [614/7,893], men: n = 364 [58.5%]). Only 9.7% of practitioners used questionnaires to quantify the level of dental anxiety. The members of both JSDH and JDSA group used questionnaires more frequently than members of the JSDH only (19% and 7.1%, respectively; Bonferroni corrected p, BMC Oral Health, 22, art. no. 38; 2022

Background The treatment of meniscus injuries combined with anterior cruciate ligament (ACL) reconstruction would be important to improve outcomes after ACL reconstruction. However, the effects of treatment methods for meniscus after ACL reconstruction have not been thoroughly investigated. The objective of this study was to investigate the effects of treatment methods for meniscus on clinical and radiological outcomes at 2 years after ACL reconstruction. Methods Three-hundred and eighteen patients with primary ACL reconstruction using autologous hamstring tendon registered in our multicenter study database and who were followed up for 2 years were included. They were then divided into 3 groups, the no meniscal lesion/untreated group (n = 149), the meniscal repair group (n = 139), and the meniscal resection group (n = 30). Patient-based subjective evaluations (Lysholm score, Knee injury and Osteoarthritis Outcome score and International Knee Documentation Committee subjective score), objective evaluations (Lachman test, pivot shift test and KT measurement), and radiological measurements (medial and lateral joint space width) were compared among the 3 groups preoperatively and at 2 years follow-up. Results All subjective scores and objective evaluations significantly improved in all groups without significant differences among the groups postoperatively. Regarding radiological findings, the medial joint space width significantly decreased only in the resection group during the 2-year period, and the medial joint space width in the resection group was significantly smaller than that of the other groups at the 2-year follow-up. Moreover, the medial joint space width significantly decreased during the 2-year period when MM was resected. Conclusions In radiological findings, medial meniscus resection decreased medial joint space width two years after ACL reconstruction. On the other hand, treatment methods for meniscus neither significantly affected subjective nor objective findings until the 2-year follow-up. Level of evidence Ⅱ, Cohort study.

One anastomosis gastric bypass (OAGB) leads to improvement in glucose homeostasis; however, the mechanism of this beneficial effect is not fully understood. Increased serum free fatty acid (FFA) concentrations in obese subjects contribute to the development of insulin resistance and type 2 diabetes.The authors hypothesized that improvement in glucose homeostasis after OAGB may be associated with a decrease in FFA concentration.Serum FFA levels were measured by gas chromatography-mass spectrometry before and 3 months after OAGB and, for comparison, in patients who underwent laparoscopic sleeve gastrectomy (LSG). Serum insulin was assayed by immunoenzymatic method, and other parameters by standard laboratory methods.OAGB resulted in a large decrease in FFA levels and great improvement in insulin sensitivity. These effects in patients after LSG were less prominent.Results suggest that decreased serum FFA levels after OAGB contribute to resolution of insulin sensitivity after this type of bariatric surgery.

Although the methods for medical education continue to evolve due to the development of medicines, the cadaver dissection course still plays a fundamental role. The cadaver dissection course allows students to learn to handle instruments correctly while actively exploring three-dimensional anatomy. However, dissection comes with the risk of accidental injury. In recent years, the number of classes offered for the cadaver dissection course has decreased while the amount of knowledge required in clinical medicine has increased. Simulation-based education has been proven to be an effective educational method that enhances the development of practical skills by integrating learners' knowledge and skills. This study aimed to investigate the effect of SBE as a preparatory education course when taken prior to a medical student's enrollment in the cadaver dissection course. In the present study, an SBE assuming practical cadaver dissection course was performed in the Clinical Simulation Center. The frequency of injury rates per 1,000 hours of cadaver dissection course was significantly less in 2017 and 2018 compared to that in 2016. Two years after the implementation of the simulation-based education, average student self-efficacy scores and written examination scores significantly increased, whereas self-contentment scores were relatively unchanged. The results showed that the implementation of simulation-based education decreased the incidence of injuries and improved students' overall self-efficacy scores and increased acquisition of knowledge evident on written examination score. Therefore, simulation-based education as a preparatory education course may effectively promote the combined development of dissection skills and anatomical knowledge in the subsequent fundamental cadaver dissection course.

INTRODUCTION The ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE study in Japan (OVERCOME [Japan]) assessed the impact and burden of migraine in Japan. METHODS OVERCOME (Japan) was a cross-sectional, observational, population-based web survey of Japanese people with migraine conducted between July and September 2020. The burden and impact of migraine were assessed using the Migraine Disability Assessment (MIDAS), Migraine-Specific Quality-of-Life Questionnaire (MSQ), Migraine Interictal Burden Scale (MIBS-4), and Work Productivity and Activity Impairment-Migraine scale. Results were stratified by average number of monthly headache days (0-3, 4-7, 8-14, ≥ 15). RESULTS In total, 17,071 Japanese people with migraine completed the survey. Of these, 14,033 (82.2%) met International Classification of Headache Disorders, 3rd edition criteria for migraine and 9667 (56.6%) reported a physician diagnosis of migraine. Overall, 20.7% of respondents experienced moderate-to-severe disability (MIDAS). Moderate-to-severe interictal burden (MIBS-4) was experienced by 41.5% of respondents. MSQ scores in all domains were lowest in respondents with the most frequent headaches (≥ 15 monthly headache days) and highest in those with the lowest frequency headaches (≤ 3 monthly headache days), indicating poorer quality of life in those with more frequent headaches. Work time missed due to migraine (absenteeism) increased with increasing headache frequency, from 3.8 to 6.2%; presenteeism affected 29.8-49.9% of work time. Although migraine burden was greatest in people with the most frequent headaches, those with the lowest headache frequency still experienced substantial disability, interictal burden, and impacts on productivity and quality of life. There was also substantial unmet need for migraine care: 36.5% of respondents had ever hesitated to seek medical care for their headaches, and 89.8% had never used preventive medication. CONCLUSION In Japan, the burden of migraine and barriers to migraine care are substantial. Improving patient awareness and healthcare provider vigilance may help improve patient outcomes.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulates as mature and furin-cleaved forms, which differ in their properties to degrade low-density lipoprotein (LDL) receptors.In this study, we sought to investigate whether PCSK9 subtypes associate with atherosclerotic cardiovascular events.We investigated 1,436 statin-naive Japanese subjects without any cardiovascular disease in the Suita Study, an epidemiologic Japanese cohort study. Total, mature, and furin-cleaved PCSK9 levels were measured by means of enzyme-linked immunosorbent assay. The occurrence of coronary and stroke events were compared in subjects stratified by PCSK9 level tertile.Total, mature, and furin-cleaved PCSK9 levels were associated with non-high-density lipoprotein cholesterol (allFurin-cleaved but not total and mature PCSK9 was associated with both LDL cholesterol and hs-CRP and predicted future coronary events in the primary prevention settings. Our findings provide pathophysiological insights into the properties of PCSK9 subtypes in association with coronary events.

Alveolar soft part sarcoma is a rare soft tissue neoplasm that accounts for approximately 1% of all sarcomas and is usually identified in the extremities in adults. The occurrence of alveolar soft part sarcoma in the orbit is extremely rare, estimated at approximately 5% – 15% among all cases of alveolar soft part sarcoma . Here, we present a case of 29-year-old woman with orbital alveolar soft part sarcoma. We describe the magnetic resonance and F-18 2-fluoro-2-deoxy-D-glucose-position emission tomography/computed tomography findings of this case. This young woman had a spindle-shaped mass. A higher signal compared to the extraocular muscle on T1-weighted images, numerous flow voids on T2-weighted images, and intense enhancement could be key findings of this disease.

Introduction The objective was to describe the clinical characteristics, disease profile and outcome of patients referred from a regional hospital Emergency Centre (EC) to the Intensive Care Unit (ICU). Methods A retrospective review was performed using data extracted from the Integrated Critical Care Electronic Database (iCED). Data were extracted from the database with respect to patient characteristics, Society of Critical Care Medicine (SCCM) grading, and outcome of the ICU referral. Modified early warning scores (MEWS) were calculated from EC referral data. Results There were a total of 2187 referrals. Of these, 56.3% (1231/2187) were male. The mean age of referrals was 36 years. Of the referred patients, 41.5% (907/2187) were initially accepted for admission. A further 378 patients were accepted for admission after a follow up ICU review. Medical conditions accounted for the majority of patient referrals, followed by general surgery and trauma. Most patients initially accepted to ICU were classified as SCCM I and II and had a mean MEWS of 4. Almost half of the patients experienced a delay in admission, most commonly due to a lack of ICU bed availability. ICU mortality was 13.6% for patients admitted from the EC. Discussion The EC population referred to the ICU was young with a high burden of medical and trauma conditions. Decisions to accept patients to ICU are limited by available resources, and there was a need to apply ICU triage criteria. Delays in the transfer of ICU patients from the EC increase the workload and contribute to EC crowding.

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

OBJECTIVE To compare the prospective risk of stillbirth between women with and without a stillbirth in their first pregnancy. METHODS We conducted a cohort study using perinatal data from Finland, Malta, and Scotland. Women who had at least two singleton deliveries were included. The exposed and unexposed cohorts comprised women with a stillbirth and live birth in their first pregnancy, respectively. The risk of stillbirth in any subsequent pregnancy was assessed using a Cox proportional hazards model. Time-to-event analyses were conducted to investigate whether first pregnancy outcome had an effect on time to or the number of pregnancies preceding subsequent stillbirth. RESULTS The pooled data set included 1,064,564 women, 6,288 (0.59%) with a stillbirth and 1,058,276 with a live birth in a first pregnancy. Compared with women with a live birth, women with a stillbirth in the first pregnancy were more likely to have a subsequent stillbirth (adjusted hazard ratio [aHR] 2.25, 95% CI 1.86-2.72). For women with more than two pregnancies, the difference in risk of subsequent stillbirth between the two groups increased with the number of subsequent pregnancies. Maternal age younger than 25 years or 40 years and older, smoking, low socioeconomic status, not having a partner, pre-existing diabetes, preeclampsia, placental abruption, or delivery of a growth-restricted neonate in a first pregnancy were independently associated with subsequent stillbirth. Compared with women with a live birth in the first pregnancy, women with a stillbirth were more likely to have another pregnancy within 1 year. The absolute risk of stillbirth in a subsequent pregnancy for women with stillbirth and live birth in a first pregnancy were 2.5% and 0.5%, respectively. CONCLUSION Compared with women with a live birth in a first pregnancy, women with a stillbirth have a higher risk of subsequent stillbirth irrespective of the number and sequence of the pregnancies. Despite high relative risk, the absolute risk of recurrence was low.

Massive weight loss might lead to excess skin folds causing functional, physical, and psychosocial discomfort. Following bariatric procedures, an increasing number of patients are seeking lower body contouring surgery (LBCS). The proportion of bariatric patients who undergo LBCS is largely unknown. The aim of this current study was to analyse the incidence and realization of LBCS in bariatric patients in Finland. National retrospective register linkage study including all adult patients who received bariatric surgery in Finland during 1998-2016. The data were obtained from the Finnish national health registers maintained by the Finnish Institute for Health and Welfare. Altogether 1089 (14.1%) of 7703 bariatric patients underwent LBCS during the study period. The majority of the LBCS procedures were abdominoplasty (89%). Median latency between bariatric surgery and LBCS was 31 months. The patients with LBCS were younger (p

The May-Hegglin anomaly is characterized by inherited thrombocytopenia, giant platelets, and leukocyte cytoplasmic inclusion bodies. The Fechtner, Sebastian, and Epstein syndromes are associated with mutations of the MYH9-coding nonmuscle myosin heavy chain ⅡA, similar to the May-Hegglin anomaly, and are together classified as MYH9 disorders. MYH9 disorders may include symptoms of Alport syndrome, including nephritis and auditory and ocular disorders. A 6-year-old boy was diagnosed with an MYH9 disorder after incidental discovery of hematuria and proteinuria. Focal segmental glomerulosclerosis was detected on renal biopsy. However, despite no prior bleeding diatheses, he developed a large post-biopsy hematoma despite a preprocedural platelet transfusion calculated to increase the platelet count from 54,000/μL to >150,000/μL. Idiopathic thrombocytopenic purpura is a major cause of pediatric thrombocytopenia following acute infection or vaccination, and patients with MYH9 disorders may be misdiagnosed with idiopathic thrombocytopenic purpura and inappropriately treated with corticosteroids. Careful differential diagnosis is important in thrombocytopenic patients with hematuria and proteinuria for the early detection of thrombocytopenia. Patients with MYH9 disorders require close follow-up and treatment with angiotensin Ⅱ receptor blockers to prevent the onset of progressive nephritis, which may necessitate hemodialysis or renal transplantation. The need for renal biopsy in patients with MYH9 disorders should be carefully considered because there could be adverse outcomes even after platelet transfusion.

Objective Oxidation of low-density lipoprotein (LDL) may promote atherosclerosis, whereas the reverse transport of oxidized lipids by high-density lipoprotein (HDL) may contribute to atheroprotection. To provide insights into the associations of lipoprotein lipid oxidation markers with lipoprotein subclasses at the population level, we investigated the associations of oxidized HDL lipids (oxHDLlipids) and oxidized LDL lipids (oxLDLlipids) with lipoprotein subclasses in a population-based cross-sectional study of 1395 Finnish adults ages 24–39 years. Methods The analysis of oxidized lipids was based on the determination of the baseline level of conjugated dienes in lipoprotein lipids. A high-throughput nuclear magnetic resonance (NMR) platform was used to quantify circulating lipoprotein subclass concentrations and analyze their lipid compositions. Results OxHDLlipids were mainly not associated with lipoprotein subclass lipid concentrations and lipid composition after adjustment for Apolipoprotein-A1 (Apo-A1), waist circumference and age. OxLDLlipids were associated with several markers of lipoprotein subclass lipid concentrations and composition after adjustment for Apolipoprotein-B (Apo-B), age and waist circumference. Several measures of HDL and LDL subclasses, including phospholipid and triglyceride composition, associated directly with oxLDLlipids. Cholesterol ester and free cholesterol composition in HDL and LDL associated inversely with oxLDLlipids. Conclusion We conclude that these results do not support the idea that HDL's particle size or composition would reflect its functional capacity in the reverse transport of oxidized lipids. On the contrary, oxLDLlipids were associated with the entire lipoprotein subclass profile, including numerous associations with the compositional descriptors of the particles. This is in line with the suggested role of LDL oxidation in atherogenesis.

The primary aim of this study was to observe the change in obstetric anal sphincter tear rates in instrumental deliveries during one decade. Secondly, the changes in non-instrumental deliveries were followed.Data from all deliveries at Hudiksvall Hospital, Sweden 2010-2011 and 2016-2017 were collected. The change of OASIS rate during instrumental deliveries was the most important. Statistical significances were calculated by using chi-square test, test for relative proportions, and Students t-test, where appropriate.The total incidence of OASIS decreased significantly (from 2.54% to 0.73%,Based on the results of our study the manual protection of the perineum reduces the risk of OASIS in instrumental delivery significantly.

BackgroundAntipsychotics are increasingly used among women of childbearing age and during pregnancy.ObjectiveTo determine whether children exposed to antipsychotics in utero are at increased risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD), accounting for maternal diagnoses of bipolar, psychotic and other psychiatric disorders.DesignPopulation-based cohort study, including a sibling analysis.SettingNationwide data on all pregnant women and their live-born singletons in Denmark (1997-2017), Finland (1996-2016), Iceland (2004-2017), Norway (2004-2017), and Sweden (2006-2016).Participants4 324 086 children were eligible for inclusion to the study cohort.InterventionAntipsychotic exposure in utero, assessed by pregnancy trimester, type of antipsychotic, and varying patterns of use.Main outcome measuresNon-mutually exclusive diagnoses of ADHD and ASD. We used Cox proportional hazard models to calculate hazard ratios (HRs) controlling for maternal psychiatric disorders and other potential confounding factors.FindingsAmong 4 324 086 singleton births, 15 466 (0.4%) were exposed to antipsychotics in utero. During a median follow-up of 10 years, we identified 72 257 children with ADHD and 38 674 children with ASD. Unadjusted HRs were raised for both outcomes but shifted substantially towards the null after adjustment; 1.10 (95%CI 1.00 to 1.27) for ADHD and 1.12 (0.97 to 1.29) for ASD. Adjusted HRs remained consistent by trimester of exposure and type of antipsychotic. Comparing in utero exposure with pre-pregnancy use yielded HRs of 0.74 (0.62 to 0.87) for ADHD and 0.88 (0.70 to 1.10) for ASD. Sibling analyses yielded HRs of 1.14 (0.79 to 1.64) for ADHD and 1.34 (0.75 to 2.39) for ASD.DiscussionOur findings suggest little or no increased risk of child ADHD or ASD after in utero exposure to antipsychotics.Clinical implicationsResults regarding child neurodevelopment are reassuring for women who need antipsychotics during pregnancy.

PURPOSE This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer.

Background/objectives Oxylipins are polyunsaturated fatty acid derivatives involved in the regulation of various processes, including chronic inflammation, insulin resistance and hepatic steatosis. They can be synthesized in various tissues, including adipose tissue. There is some evidence that obesity is associated with the deregulation of serum oxylipin levels. The aim of this study was to evaluate the effect of bariatric surgery (one-anastomosis gastric bypass) on the serum levels of selected oxylipins and their fatty acid precursors and to verify the hypothesis that their changes after surgery can contribute to the resolution of inflammation. Moreover, we compared the oxylipin levels (prostaglandin E2, 13-HODE, maresin 1 and resolvin E1), fatty acids and the expression of enzymes that synthesize oxylipins in adipose tissue of lean controls and subjects with severe obesity. Subjects/methods The study included 50 patients with severe obesity that underwent bariatric surgery and 41 subjects in lean, control group. Fatty acid content was analyzed by GC-MS, oxylipin concentrations were measured with immunoenzymatic assay kits and real-time PCR analysis was used to assess mRNA levels in adipose tissue. Results Our results show increased expression of some enzymes that synthesize oxylipins in adipose tissue and alterations in the levels of oxylipins in both adipose tissue and serum of subjects with obesity. After bariatric surgery, the levels of anti-inflammatory oxylipins increased, whereas pro-inflammatory oxylipins decreased. Conclusions In patients with obesity, the metabolism of oxylipins is deregulated in adipose tissue, and their concentrations in serum are altered. Bariatric surgery modulates the serum levels of pro- and anti-inflammatory oxylipins, which may contribute to the resolution of inflammation.

Publisher Copyright: © 2021 The Author(s). Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. Expanding clinical strategies to identify high risk groups for psychotic and bipolar disorders is a research priority. Considering that individuals diagnosed with psychotic and bipolar disorder are at high risk of self-harm, we hypothesised the reverse order relationship would also be true (ie, self-harm would predict psychotic/bipolar disorder). Specifically, we hypothesised that hospital presentation for self-harm would be a marker of high risk for subsequent development of psychotic/bipolar disorder and sought to test this hypothesis in a large population sample. This prospective register-based study included everyone born in Finland in 1987, followed until age 28 years (N = 59 476). We identified all hospital records of self-harm presentations, as well as all ICD-10 healthcare registrations of first diagnoses of psychotic and bipolar disorders. Cox proportional hazards models were used to assess the relationship between self-harm and psychotic/bipolar disorders. Of all individuals who presented to hospital with self-harm (n = 481), 12.8% went on to receive a diagnosis of psychosis (hazard ratio [HR] = 6.03, 95% confidence interval [CI] 4.56-7.98) and 9.4% a diagnosis of bipolar disorder (HR = 7.85, 95% CI 5.73-10.76) by age 28 years. Younger age of first self-harm presentation was associated with higher risk-for individuals who presented before age 18 years, 29.1% developed a psychotic or bipolar disorder by age 28 years. Young people who present to hospital with self-harm are at high risk of future psychotic and bipolar disorders. They represent an important cohort for the prevention of serious mental illness.

Funder: Nederlandse Organisatie voor Wetenschappelijk Onderzoek; doi: http://dx.doi.org/10.13039/501100003246, Funder: ZonMw; doi: http://dx.doi.org/10.13039/501100001826, Funder: Research Institute for Diseases in the Elderly, Funder: Ministerie van Onderwijs, Cultuur en Wetenschap; doi: http://dx.doi.org/10.13039/501100003245, Funder: Health Promotion Administration, Ministry of Health and Welfare; doi: http://dx.doi.org/10.13039/100013227, Funder: Municipality of Rotterdam, Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = -0.0264, p value = 3.5 × 10-8) in the discovery panel and was replicated in replication panel (beta = -0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10-13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

Core body temperature (CBT) is considered a valuable marker for circadian rhythm. This study aimed to investigate the changes in CBT that are associated with the symptoms of circadian rhythm sleep-wake disorder (CRSWD) post-treatment in children.Twenty-eight school-age children [10 boys and 18 girls; mean age (±standard deviation), 13.68 ± 0.93 years] who were admitted to our hospital with CRSWD underwent treatment for 6-8 weeks according to the following protocol: lights-out for sleep at 21:00; phototherapy for waking at 6:00 or 7:00; light exercise everyday (eg, a 20- to 30-min walk). CBT was continuously measured for 24 h on the first day of admission and on the first day after treatment.The mean time of sleep onset/offset (±standard deviation; in hours:minutes) 1 week before admission and 1 week after treatment were 23:53 ± 2:26/9:58 ± 2:15 and 21:17 ± 0:19/6:46 ± 0:32, respectively. The mean times of sleep onset and offset measured post-treatment were significantly earlier than those measured pre-treatment (p 0.001). The mean CBT and mean minimum CBT during sleep were significantly lower on the first day post-treatment than on the first day of admission (p = 0.011 and p 0.001, respectively).Symptom improvements in patients with CRSWD were associated with a decrease in CBT during sleep, suggesting that CBT may be a biomarker for improvements in CRSWD. These results help elucidate the cause of this sleep disorder.

BackgroundNeurological manifestations of coronavirus disease 2019 (COVID-19) are increasingly recognized and include encephalopathy, although direct infection of the brain by SARS-CoV-2 remains controversial. We herein report the clinical course and cytokine profiles of a patient with severe SARS-CoV-2-related encephalopathy presenting aphasia.Case presentationAn 81-year-old man developed acute consciousness disturbance and status epileptics several days after SARS-CoV-2 infection. Following treatment with remdesivir and dexamethasone, his consciousness and epileptic seizures improved; however, amnestic aphasia and agraphia remained. Two months after methylprednisolone pulse and intravenous immunoglobulin, his neurological deficits improved. We found increased levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1), but not IL-2 and IL-10 in the serum and cerebrospinal fluid (CSF), and the levels of serum IL-6 and MCP-1 were much higher than those in the CSF. The level of IL-8 in the CSF after immunotherapy was four times higher than that before immunotherapy.ConclusionThe cytokine profile of our patient was similar to that seen in severe SARS-CoV-2-related encephalopathy. We demonstrated (i) that the characteristic aphasia can occur as a focal neurological deficit associated with SARS-CoV-2-related encephalopathy, and (ii) that IL8-mediated central nervous system inflammation follows systemic inflammation in SARS-CoV-2-related encephalopathy and can persist and worsen even after immunotherapy. Monitoring IL-8 in CSF, and long-term corticosteroids may be required for treating SARS-CoV-2-related encephalopathy.

AIM The potential for immunotherapy to prevent asthma development has become a hot topic. This prompted us to revisit data from an early study that examined allergic sensitisation on bronchial hyperresponsiveness (BHR) in children with and without respiratory symptoms. Unlike previous studies, it used both indirect and direct test methods. METHODS The study was conducted in Kuopio, Finland, in 1994 and 247 children (55.1% boys) with a mean age 10.5 ± 1.7 years were recruited using a school survey: 165 with lower respiratory symptoms and 82 healthy controls. Each child underwent a 6-min free-running test and a methacholine test with a cumulative dose of 4900 µg. All participants underwent skin-prick tests: 127were sensitised and 120 were non-sensitised. RESULTS There were no significant differences in lung function between the sensitised and non-sensitised children. However, sensitisation was associated with BHR which was measured by both the methacholine test (2400 µg versus >4900 µg, p

BackgroundLow-vacuum scanning electron microscopy (LV-SEM) is applied to diagnostic renal pathology.MethodsTo demonstrate the usefulness of LV-SEM and to clarify the optimal conditions of pathology samples, we investigated the alterations of glomerular basement membrane (GBM) and podocytes in control and experimental active Heymann nephritis (AHN) rats by LV-SEM.ResultsOn week 15 following induction of AHN, spike formation on GBM with diffuse deposition of IgG and C3 developed. Using LV-SEM, diffuse crater-like protrusions were clearly noted three-dimensionally (3D) on surface of GBM in the same specimens of light microscopy (LM) and immunofluorescence (IF) studies only after removal coverslips or further adding periodic acid-silver methenamine (PAM) staining. These 3D ultrastructural findings of GBM surface could be detected in PAM-stained specimens by LV-SEM, although true GBM surface findings could not be obtained in acellular glomeruli, because some subepithelial deposits remained on surface of GBM. Adequate thickness was 1.5–5 μm for 10% formalin-fixed paraffin-embedded (FFPE) and 5–10 μm for the unfixed frozen sections. The foot processes and their effacement of podocytes could be observed by LV-SEM using 10%FFPE specimens with platinum blue (Pt-blue) staining or double staining of PAM and Pt-blue. These findings were obtained more large areas in 2.5% glutaraldehyde-fixed paraffin-embedded (2.5%GFPE) specimens.ConclusionOur findings suggest that LV-SEM is a useful assessment tool for evaluating the alterations of GBM and podocytes in renal pathology using routine LM and IF specimens, as well as 2.5%GFPE specimens.

Objectives To assess the safety and effectiveness of mycophenolate mofetil (MMF) in Japanese adults with lupus nephritis (LN) in real-world clinical practice. Methods This multicentre, prospective, post-marketing surveillance study investigated the effectiveness and safety of MMF, as induction or maintenance therapy, in LN patients. Primary endpoints were adverse drug reactions (ADRs), changes in renal function from baseline, and relapse rate (RR) after 6 months in the maintenance group, estimated using the Kaplan–Meier method. Complete remission (CR) and partial remission (PR) were estimated by renal measurements. Results Overall, 112 patients were enrolled in the induction group and 340 in the maintenance group. Of these 452 patients, 418 were evaluable for safety and 396 for effectiveness. Eighty-three patients (19.85%) experienced ADRs, most commonly herpes zoster (3.34%) and diarrhoea (3.11%). Serious ADRs occurring in more than three patients were cytomegalovirus infections (1.43%), acute pyelonephritis (0.71%), and herpes zoster (0.71%). One patient died from herpes zoster disseminated. CR and PR were 19.54% and 44.82%, respectively, in the induction group, and 40.62% and 66.16%, respectively, in the maintenance group. RR in the maintenance group was 0.70%. Conclusions The tolerability of MMF is in line with that reported in other studies. Since the average dose of MMF was

Zusammenfassung Einleitung und Ziel Seit dem Frühjahr 2020 hat die COVID‑19-Pandemie nahezu alle Bereiche des gesellschaftlichen Lebens erheblich eingeschränkt, was bei vielen Menschen sowohl zu psychischen als auch zu körperlichen Belastungen geführt hat. In diesem Artikel nehmen wir die Situation von trans Personen in den Blick, die infolge ihrer gesellschaftlichen Diskriminierung und Marginalisierung sowie spezifischer, gesundheitsbezogener Anliegen durch eine besondere Vulnerabilität gekennzeichnet sein können. Methoden Unter Beachtung partizipativer Elemente haben wir mit einer Online-Querschnitterhebung im Zeitraum vom 01.05.2020 bis zum 31.01.2021 die psychische und physische Gesundheit von trans Personen im deutschsprachigen Raum sowie deren Zugang zur Trans-Gesundheitsversorgung während der COVID‑19-Pandemie untersucht. Ergebnisse Trans Personen erleben seit Beginn der COVID‑19-Pandemie vermehrt Barrieren sowohl bei geschlechtsangleichenden Behandlungen und psychosozialen Unterstützungsangeboten als auch im Bereich der COVID‑19-bezogenen medizinischen Versorgung. Im Vergleich zur Gesamtbevölkerung berichten sie übermäßig häufig von somatischen Erkrankungen, auch von solchen, die ein erhöhtes Risiko für schwere Verläufe einer COVID‑19-Infektion darstellen. Außerdem berichten die Teilnehmenden verschiedene Faktoren, die ein Risiko für eine erhöhte psychische Belastung darstellen können (z. B. Zugehörigkeit zu einer Minderheit aufgrund nicht-heterosexueller Orientierung, niedriges Einkommen). Diskussion Die Ergebnisse unserer Untersuchung weisen darauf hin, dass bisherige Vulnerabilitäten für gesundheitliche Probleme und der eingeschränkte Zugang zu einer qualifiziert informierten Trans-Gesundheitsversorgung durch die Folgen der COVID‑19-Pandemie verschärft wurden.

BackgroundLong-term ‘not in education, employment or training’ (NEET) status is an important indicator of youth marginalisation.AimsTo carry out a comprehensive overview of the associations between different psychiatric illnesses and long-term NEET status.MethodWe used the register-based 1987 Finnish Birth Cohort study, which includes all live births in Finland during that year. The analyses comprised 55 273 individuals after exclusions for intellectual disability, death or emigration. We predicted that psychiatric disorders, diagnosed by specialist services between 1998 and 2007 when the cohort were 10–20 years of age, would be associated with subsequent long-term NEET (defined as NEET for at least 5 years between 2008 and 2015, when they were 20–28 years of age).ResultsIn total, 1438 individuals (2.6%) were long-term NEET during follow-up and the associations between long-term NEET and the 11 diagnostic categories we studied were statistically significant (P < 0.001). In multivariate models we included sociodemographic characteristics and upper secondary education as covariates, and the highest effect sizes, measured by odds ratios (OR) with 95% confidence intervals (CI), were found for psychosis (OR = 12.0, 95% CI 9.5–15.2) and autism spectrum disorder (OR = 17.3, 95% CI 11.5–26.0). If individuals had not successfully completed this education, 70.6% of those with autism spectrum disorder and 48.4% of those with psychosis were later long-term NEET.ConclusionsAdolescents who receive treatment for psychiatric disorders, particularly autism spectrum disorder or psychosis, need support to access education and employment. This could help to prevent marginalisation in early adulthood.

The presence of tertiary lymphoid structure (TLS) in tumor tissues has been reported to be a factor associated with a good prognosis in several types of cancers. However, the relationship between TLS formation and peripheral blood findings remains unclear. The purposes of the study were to evaluate the effect of the presence of TLS on survival and determine the peripheral blood characteristics associated with TLS formation in non-small cell lung cancer (NSCLC) patients. A total of 147 consecutive NSCLC patients who underwent lung resection at Fukushima Medical University Hospital between 2013 and 2017 were enrolled. TLS expression was evaluated, and the relationships between clinical parameters and outcomes were analyzed. Peripheral blood mononuclear cells (PBMCs) were further analyzed by mass cytometry to characterize the TLS-positive microenvironment. Forty-six patients had high TLS expression, and the remaining 101 patients had low TLS expression. In stage II to IV patients (n = 35), disease-free survival was longer in the high TLS expression group (p = 0.027). A low neutrophil to lymphocyte ratio (NLR)

Study design A cross-sectional study of the Northern Finland Birth Cohort 1966 (NFBC1966). Objective To evaluate the association of lumbosacral transitional vertebrae (LSTV) with low back pain (LBP) and associated degenerative findings using MR imaging. Summary of background data LSTV is a common finding with a prevalence of 10% to 29%. LSTV causes biomechanical alterations leading to accelerated lumbar degeneration. However, its association with degenerative findings on MRI and LBP is unclear. Methods 1468 lumbar spine MRI scans from the NFBC1966 acquired at a mean age of 47 years were assessed for the presence of LSTV and degenerative changes. Castellvi classification was utilized to identify LSTV anatomy. Additionally, 100 controls without LSTV were collected. Self-reported LBP with a duration of >30 days in the past year was deemed clinically relevant. For the statistical analyses, chi square test, independent samples t-test and multinomial logistic regression analyses were used. Results LSTV was found in 310 (21.1%) subjects. After adjusting for age, sex and disc degeneration (DD) sum, subjects with Castellvi type III reported prolonged LBP significantly more frequently than the controls (OR = 8.9, p = 0.001). We observed a higher prevalence of facet degeneration (FD) at all levels from L3/L4 to L5/S1 in type I, and L3/L4 to L4/L5 in types II-IV. DD was more prevalent at L4/L5 in types II-IV. Disc protrusion/extrusion occurred more frequently at L3/L4 and L4/L5 in type II, and at L3/L4 in type III. Castellvi type II had a higher prevalence of type 1 Modic changes at all levels from L3/L4 to L5/S1, and type IV had a higher prevalence of any Modic changes at L4/L5. Conclusion LSTVs were a common finding within this study, and Castellvi type III LSTVs were associated with LBP. Degenerative findings were associated with LSTV anatomy and occurred more commonly above the transitional level.Level of Evidence: 3.

Background Thyroid crisis is a life-threatening condition in thyrotoxic patients. Although differentiated thyroid cancer is one of the causes of hyperthyroidism, reports on thyroid crisis caused by thyroid cancer are quite limited. Here, we describe a case of thyroid crisis caused by metastatic thyroid cancer. Case presentation A 91-year-old woman was admitted to our hospital because of loss of appetite. Two years prior to this hospitalization, she presented with subclinical thyrotoxicosis and was diagnosed with histologically unidentified thyroid cancer with multiple metastases, and she refused aggressive medical interventions. On admission, she exhibited extreme thyrotoxicosis, and the presence of fever, severe tachycardia, impaired consciousness, and heart failure revealed the presence of thyroid crisis. All thyroid autoantibodies were negative. Multidisciplinary conservative treatment was initiated; however, she died on the fifth day after admission. Autopsy revealed the presence of primary anaplastic thyroid carcinoma and multiple metastatic foci arising from follicular thyroid carcinoma. Both primary and metastatic follicular thyroid carcinoma likely induced thyrotoxicosis, which could have been exacerbated by anaplastic thyroid carcinoma. Conclusions Even though the trigger of thyroid crisis in this patient is not clear, the aggravated progression of her clinical course suggests that careful monitoring of thyroid hormones and appropriate intervention are essential for patients with thyroid cancer.

Background/purpose Radiotherapy for head and neck cancer often causes severe oral mucositis. The purpose of this retrospective study was to further examine the risk factors for developing severe oral mucositis in patients with oral cancer undergoing radiotherapy as a compliment to a previous study performed by our group. Materials and methods A total of 181 patients with oral cancer undergoing radiotherapy were enrolled in the study. The association between a number of potential risk factors and grade 3 oral mucositis were analyzed using the cox proportional hazard model and a logistic regression analysis. Results Grade 3 oral mucositis occurred in 56 patients. The cox proportional hazard model analysis revealed that those with lower hemoglobin levels, concurrent cisplatin and cetuximab administration, and a larger number of teeth showed a significantly higher incidence of severe oral mucositis. Logistic regression analysis revealed that patients who had lower hemoglobin levels, received concurrent cisplatin or cetuximab treatment, and were not administered pilocarpine showed a significantly higher incidence of severe oral mucositis. The presence of teeth may stimulate the oral mucosa and become a risk factor for mucositis, and the administration of pilocarpine might reduce the risk. Conclusion This study describes the risk factors of severe radiation-induced oral mucositis in oral cancer patients and shows the possibility of risk reduction by pilocarpine. This information could help patients avoid painful mucositis.

Organized hematoma (OH) is benign tumor in the maxillary sinus. The standard treatment for OH is complete surgical resection, however massive bleeding can occur during the procedure, albeit rarely. Some reports have suggested preoperative embolization is useful for reducing the volume of intraoperative bleeding. We report 3 cases of OH in the maxillary performed preoperative embolization. We identified the feeding arteries by angiography or IVR-CT, and we embolized them using Gelatin sponge particles. The embolized artery was the maxillary artery or both the maxillary and the facial artery. There were no major complications as a result of embolization. The mean fluoroscopy time was 35.8 minutes, and the mean fluoroscopy dose was 329.3 mGy. Tumor resection was performed the next day after arterial embolization. The mean bleeding volume for surgery was 383.3 ml, and the mean operative time was 194 minutes. No recurrence was observed in any of the cases over a 4-year follow-up period. We considered that it is possible that preoperative artery embolization is useful for decreasing intraoperative bleeding volume. Although the methods and usefulness of embolization await future reports, it is a technique that should be considered preoperatively because of its potential to prevent massive bleeding.

OBJECTIVE Dobutamine stress echocardiography (DSE) is not always feasible in patients with low-gradient severe aortic stenosis (LG-SAS), and there are limited data available on the resting echocardiographic predictors for true-severe aortic stenosis (TSAS). This study investigated resting echocardiographic predictors for TSAS. METHODS Clinical data of 106 LG-SAS patients who underwent DSE were retrospectively analyzed. LG-SAS was defined as an aortic valve area index (AVAi)

Objective In Japan, both medical oncologists and pulmonologists treat lung cancer patients; however, the difference in their attitude toward palliative care referral is unknown. Thus, we retrospectively investigated the difference in attitudes toward palliative care referral between medical oncologists and pulmonologists in Japan. Methods We retrospectively reviewed the charts of patients with thoracic malignancy who died at Shimane University Hospital between June 2011 and October 2015. We compared the patients' demographics and medical history according to their doctor's specialty (i.e., medical oncologist or pulmonologist). Results We identified 182 patients, among whom 90 were treated by medical oncologists and 56 by pulmonologists at the outpatient clinic. Thirty-six patients did not undergo outpatient clinic treatment. Out of 59 patients, 22 (37.3%) referred by medical oncologists, and 7 out of 36 patients (19.4%) referred by pulmonologists, were referred to palliative care specialists in the outpatient setting (p=0.107, Fisher's exact test). The median survival time after admission to PCU was 21 (95% CI: 13-32) and 9 (95% CI: 5-15) days among the patients treated by medical oncologists and pulmonologists, respectively (p=0.128). Conclusion Medical oncologists are more likely to refer their patients to palliative care in the outpatient setting, thus enabling patients to receive longer end of life care in the PCU. Bridging the research gap regarding differences between the physicians' attitudes toward palliative care referral may lead to patients receiving more quality palliative care. (227 words).

STUDY QUESTION Does the probability of a live birth after fresh IVF/ICSI cycles with autologous oocytes differ in early onset female cancer survivors compared to their siblings? SUMMARY ANSWER The probability of a live birth was similar in female cancer survivors and siblings after four fresh IVF/ICSI cycles. WHAT IS KNOWN ALREADY Fertility preservation strategies are rapidly being developed to help female cancer patients who wish to have children later. However, there are only a few studies available on fertility treatments and following live births in female cancer survivors before fertility preservation strategies became available. In one of them, the probability of a live birth was reduced after assisted reproductive technology with autologous oocytes in cancer survivors compared to siblings. STUDY DESIGN, SIZE, DURATION In this retrospective, register-based study, data from Finnish registers on cancer, birth and prescribed medications were merged to identify 8944 female cancer survivors (diagnosed with cancer between 1953 and 2012 at the age of 0–40 years) and 9848 female siblings of survivors eligible for IVF/ICSI treatments between January 1993 and December 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS Fresh IVF/ICSI cycles and following live birth rates (LBRs) within 22–48 weeks in cancer survivors and siblings at the age of 20–41 years were identified. A binomial regression model with log-link function was used to calculate risk ratio (RR) for live births after fresh IVF/ICSI cycles in survivors compared to siblings, adjusting for attained age and calendar time. A Poisson regression model was used to estimate incidence rate ratios (IRRs) for an IVF/ICSI treatment, as well as overall live births, including both pregnancies after fertility treatments and spontaneous pregnancies, in survivors compared to siblings. MAIN RESULTS AND THE ROLE OF CHANCE We observed an overall decreased LBR, irrespective of IVF/ICSI treatments, in cancer survivors compared to siblings (IRR 0.68, 95% CI 0.64–0.71). All in all, 179 (2.0%) survivors and 230 (2.3%) siblings were prescribed fertility drugs for IVF/ICSI treatments (IRR 0.72, 95% CI 0.62–0.84). For the first fresh IVF/ICSI cycle, the LBR was 17.2% among survivors and 15.7% among siblings (RR 1.13, 95% CI 0.72–1.87). The mean LBR after four fresh IVF/ICSI cycles was not statistically different in survivors compared to siblings. LIMITATIONS, REASONS FOR CAUTION In this study, only IVF/ICSI treatments with autologous oocytes were included. The probability of a live birth after a frozen embryo transfer or oocyte donation could not be evaluated in this study. Information on miscarriages, extrauterine pregnancies or termination of pregnancies was not available. WIDER IMPLICATIONS OF THE FINDINGS For those early onset cancer survivors, who received IVF/ICSI treatments, the probability of live birth was not different from siblings who received IVF/ICSI treatments. However, an overall decreased LBR, irrespective of IVF/ICSI treatments, was observed in cancer survivors compared to siblings, indicating that cancer survivors receiving IVF/ICSI treatments in our study consisted of a selected group with at least a moderate ovarian reserve. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by a grant from the Cancer Foundation (Finland) (grant number 130079) and by a grant from LähiTapiola. The authors have no potential conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Introduction This study aims to explore maternal and perinatal outcomes of migrant women in Iceland. Material and methods This prospective population‐based cohort study included women who gave birth to a singleton in Iceland between 1997 and 2018, comprising a total of 92 403 births. Migrant women were defined as women with citizenship other than Icelandic, including refugees and asylum seekers, and categorized into three groups, based on their country of citizenship Human Development Index score. The effect of country of citizenship was estimated. The main outcome measures were onset of labor, augmentation, epidural, perineum support, episiotomy, mode of birth, obstetric anal sphincter injury, postpartum hemorrhage, preterm birth, a 5‐minute Apgar

Background Standard treatments for small cell carcinoma of the cervix (SCCC) have not been established. In this study, we aimed to estimate the optimal treatment strategy for SCCC. Methods This was a multicenter retrospective study. Medical records of patients with pathologically proven SCCC treated between 2003 and 2016 were retrospectively analyzed. Overall survival (OS) was plotted using the Kaplan-Meier method. Log-rank tests and Cox regression analysis were used to assess the differences in survival according to stage, treatment strategy, and chemotherapy regimen. Results Data of 78 patients were collected, and after excluding patients without immunohistopathological staining, 65 patients were evaluated. The median age of the included patients was 47 (range: 24–83) years. The numbers of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stages I-IIA, IIB-IVA, IVB were 23 (35%), 34 (52%), and 8 (12%), respectively. Of 53 patients who had undergone chemotherapy, 35 and 18 received SCCC and non-SCCC regimens as their first-line chemotherapy regimen, respectively. The 5-year OS for all patients was 49%, while for patients with FIGO stages I-IIA, IIB-IVA, IVB, it was 60, 50, and 0%, respectively. The 5-year OS rates for patients who underwent treatment with SCCC versus non-SCCC regimens were 59 and 13% (p Conclusion Our results suggest that the application of an SCCC regimen such as EP or IP as first-line chemotherapy for patients with locally advanced SCCC may play a key role in OS. These findings need to be validated in future nationwide, prospective clinical studies.

This study aimed to assess the efficacy of a text messaging intervention that offered pregnancy and childbirth support. Participants included 39 primigravid women who were less than 12 weeks pregnant. Text messages were sent twice weekly to the intervention group from week 13 of pregnancy until childbirth. Outcome measures were anxiety levels, lifestyle in the month before birth, pre-birth weight, pregnancy complications, delivery complications, birth weight, thoughts regarding the text messages, and the frequency of viewing of the text messages. For the item "I engage in body stretching," the average value in the intervention group was significantly higher than that in the control group. For the item "I have regular bowel movements," the average value in the intervention group was significantly lower. Most participants reported that the intervention was at least somewhat useful. This study indicates that text messaging intervention is practical and can be used to support numerous pregnant women simultaneously at a relatively low cost. Since this is a study pilot trial, large-scale studies are necessary to improve the method and allow for the generalization of the results.

A 59-year-old, right-handed woman made many mistakes in her job in a pharmacy, despite having considerable experience working in this setting. She had a can-do attitude, but also showed no sign of remorse when she failed. Other staff grew impatient with her and she was diagnosed with frontotemporal dementia based on clinical and brain imaging findings. After diagnosis, other staff understood that the disease was the cause of her difficulties, and her work tasks and hours were changed to fit with her stereotypical behavior. This support in the workplace made it possible for her to continue her job.

Background: The International Atherosclerosis Society (IAS) has proposed “severe familial hypercholesterolemia” (FH) as a phenotype with the highest cardiovascular risk. However, whether this criteria could appropriately stratify a high-risk Japanese patient with FH remains unknown. Objectives: This study sought to characterize atherosclerotic cardiovascular diseases in IAS-defined Japanese subjects with severe FH. Methods: This study analyzed 380 clinically diagnosed subjects with heterozygous FH without any history of atherosclerotic cardiovascular diseases. Severe FH was defined as untreated low-density lipoprotein cholesterol >400 mg/dL, >310 mg/dL plus 1 high-risk feature, or >190 mg/dL plus 2 high-risk features according to IAS-proposed statement. The occurrence of first and subsequent composite outcomes (cardiac [cardiac death + coronary artery disease + coronary revascularization] and noncardiac events [stroke + peripheral artery disease] was compared between subjects with severe (n = 135) and non-severe (n = 227) FH. Results: Severe FH was identified in 40.3% of study population. They had higher low-density lipoprotein cholesterol (P < 0.001) and lipoprotein(a) (P = 0.03) levels. Moreover, they more frequently received high-intensity statin (P < 0.001), PCSK9 inhibitor (P < 0.001), and lipoprotein apheresis (P = 0.01) than nonsevere FH subjects did, which resulted in a lower on-treatment low-density lipoprotein cholesterol level of subjects with severe FH (113 ± 47.2 vs 130 ± 53.9 mg/dL; P = 0.007). However, during the 7.4-year observational period, subjects with severe FH exhibited a 9.3-, 15.4-, and 5.9-fold greater risk for first composite (P < 0.001), cardiac (P < 0.001), and noncardiac outcomes (P = 0.02), respectively. Multivariate Cox proportional hazard model consistently revealed the 7.8- and 7.9-fold elevated risks of first (P < 0.001) and of subsequent (P < 0.001) composite outcomes in subjects with severe FH. Conclusions: Japanese subjects with severe FH present profound risks of both first and subsequent atherosclerotic cardiovascular diseases in the primary prevention settings. These findings support the clinical applicability of IAS-defined severe FH in Japanese patients, which identifies those who require further stringent antiatherosclerotic management.

Quantitative understanding of pharmacokinetics of topically applied ocular drugs requires more research to further understanding and to eventually allow predictive in silico models to be developed. To this end, a topical cocktail of betaxolol, timolol and atenolol was instilled on albino rabbit eyes. Tear fluid, corneal epithelium, corneal stroma with endothelium, bulbar conjunctiva, anterior sclera, iris-ciliary body, lens and vitreous samples were collected and analysed using LC-MS/MS. Iris-ciliary body was also analysed after intracameral cocktail injection. Non-compartmental analysis was utilized to estimate the pharmacokinetics parameters. The most lipophilic drug, betaxolol, presented the highest exposure in all tissues except for tear fluid after topical administration, followed by timolol and atenolol. For all drugs, iris-ciliary body concentrations were higher than that of the aqueous humor. After topical instillation the most hydrophilic drug, atenolol, had 3.7 times higher AUCiris-ciliary body than AUCaqueous humor, whereas the difference was 1.4 and 1.6 times for timolol and betaxolol, respectively. This suggests that the non-corneal route (conjunctival-scleral) was dominating the absorption of atenolol, while the corneal route was more important for timolol and betaxolol. The presented data increase understanding of ocular pharmacokinetics of a cocktail of drugs and provide data that can be used for quantitative modeling and simulation.

Summary Objectives The objective of this study was to present a novel surgical technique involving the use of a “bipedicled vocal fold mucosal flap” to repair a mucosal defect and to evaluate the outcomes of patients in whom it was used. Material and methods This was a retrospective study of 6 clinical cases. All patients underwent surgery between November 2000 and July 2018, and all procedures were performed by the same surgeon. For the auditory-perceptual assessment, the Grade-Roughness-Breathiness-Asthenia-Strain hoarseness scale was used. We based the stroboscopic evaluation on the European Laryngological Society protocol, analyzing the parameters glottal closure, mucosal wave, and phase symmetry. Results Ages at the time of surgery ranged from 10 to 52 years, and all of the patients were male. Preexisting vocal fold lesions included polyps, cysts, a sulcus, and mucosal bridges. Among the stroboscopic parameters, only the mucosal wave differed significantly between the preoperative and postoperative periods (P = 0.046). There were also significant postoperative improvements in the overall grade of dysphonia (P = 0.025) and in the degree of breathiness (P = 0.025). Conclusions The use of a bipedicled vocal fold mucosal flap appears to promote significant improvements in the mucosal wave and in voice quality. In the patients evaluated here, the technique was used without preoperative planning. However, it proved to be a safe and appropriate means of repairing mucosal defects in the vocal folds, with the potential to preserve rheological properties and promote healing with less chance of fibrosis.

Objective There have been inconsistent findings on the associations among prematurity, poor fetal growth, and depression. We examined the associations among gestational age, poor fetal growth, and depression in individuals aged 5 to 25 years. Method We identified 37,682 case subjects based on International Classification of Diseases, Ninth Revision code 2961 and International Classification of Diseases, Tenth Revision codes F32.0-F32.9 and F33.0-F33.9 from the Care Register for Health Care, and 148,795 matched controls from the Finnish Central Population Register. Conditional logistic regression examined the associations between gestational age by each gestational week, poor fetal growth, and depression. The associations were adjusted for parental age and psychopathology, paternal immigrant status, maternal substance abuse, depression, number of previous births, marital status, socio-economic status, smoking during pregnancy, and the infant’s birthplace. Results In the adjusted models, increased risk of depression was found in children born ≤25 weeks (adjusted odds ratio [aOR] 1.89, 95% CI 1.08–3.31), at 26 weeks (aOR 2.62, 95% CI 1.49–4.61), at 27 weeks (aOR 1.93, 95% CI 1.05–3.53), and ≥42 weeks (aOR 1.11, 95% CI 1.05–1.19). In girls, extremely preterm birth was associated with depression diagnosed at 5 to 12 years (aOR 2.70, 95% CI 1.83–3.98) and 13 to 18 years (aOR 2.97, 95% CI 1.84–4.78). In boys, postterm birth (≥42 weeks) was associated with depression diagnosed at 19 to 25 years (aOR 1.28, 95% CI 1.07–1.54). Poor fetal growth was associated with an increased risk of depression in full-term infants (aOR 1.06, 95% CI 1.03–1.10) and postterm infants (aOR 1.24, 95% CI 1.08–1.43). Conclusion Preterm birth before 28 weeks of gestation appeared to play a role in the development of childhood depression. Smaller effects were also seen in postterm births, especially in boys.

Publisher's version (útgefin grein), Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (>= 65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0-100 based on the 2.5th and 97.5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target-1 billion more people benefiting from UHC by 2023-we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings Globally, performance on the UHC effective coverage index improved from 45.8 (95% uncertainty interval 44.2-47.5) in 1990 to 60.3 (58.7-61.9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2.6% [1.9-3.3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010-2019 relative to 1990-2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0.79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388.9 million (358.6-421.3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3.1 billion (3.0-3.2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968.1 million [903.5-1040.3]) residing in south Asia. Interpretation The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people-the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close-or how far-all populations are in benefiting from UHC., Lucas Guimaraes Abreu acknowledges support from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brasil (Capes) -Finance Code 001, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG). Olatunji O Adetokunboh acknowledges South African Department of Science & Innovation, and National Research Foundation. Anurag Agrawal acknowledges support from the Wellcome Trust DBT India Alliance Senior Fellowship IA/CPHS/14/1/501489. Rufus Olusola Akinyemi acknowledges Grant U01HG010273 from the National Institutes of Health (NIH) as part of the H3Africa Consortium. Rufus Olusola Akinyemi is further supported by the FLAIR fellowship funded by the UK Royal Society and the African Academy of Sciences. Syed Mohamed Aljunid acknowledges the Department of Health Policy and Management, Faculty of Public Health, Kuwait University and International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia for the approval and support to participate in this research project. Marcel Ausloos, Claudiu Herteliu, and Adrian Pana acknowledge partial support by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDSUEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. Till Winfried Barnighausen acknowledges support from the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. Juan J Carrero was supported by the Swedish Research Council (2019-01059). Felix Carvalho acknowledges UID/MULTI/04378/2019 and UID/QUI/50006/2019 support with funding from FCT/MCTES through national funds. Vera Marisa Costa acknowledges support from grant (SFRH/BHD/110001/2015), received by Portuguese national funds through Fundacao para a Ciencia e a Tecnologia (FCT), IP, under the Norma TransitA3ria DL57/2016/CP1334/CT0006. Jan-Walter De Neve acknowledges support from the Alexander von Humboldt Foundation. Kebede Deribe acknowledges support by Wellcome Trust grant number 201900/Z/16/Z as part of his International Intermediate Fellowship. Claudiu Herteliu acknowledges partial support by a grant co-funded by European Fund for Regional Development through Operational Program for Competitiveness, Project ID P_40_382. Praveen Hoogar acknowledges the Centre for Bio Cultural Studies (CBiCS), Manipal Academy of Higher Education(MAHE), Manipal and Centre for Holistic Development and Research (CHDR), Kalghatgi. Bing-Fang Hwang acknowledges support from China Medical University (CMU108-MF-95), Taichung, Taiwan. Mihajlo Jakovljevic acknowledges the Serbian part of this GBD contribution was co-funded through the Grant OI175014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. Aruna M Kamath acknowledges funding from the National Institutes of Health T32 grant (T32GM086270). Srinivasa Vittal Katikireddi acknowledges funding from the Medical Research Council (MC_UU_12017/13 & MC_UU_12017/15), Scottish Government Chief Scientist Office (SPHSU13 & SPHSU15) and an NRS Senior Clinical Fellowship (SCAF/15/02). Yun Jin Kim acknowledges support from the Research Management Centre, Xiamen University Malaysia (XMUMRF/2018-C2/ITCM/0001). Kewal Krishan acknowledges support from the DST PURSE grant and UGC Center of Advanced Study (CAS II) awarded to the Department of Anthropology, Panjab University, Chandigarh, India. Manasi Kumar acknowledges support from K43 TW010716 Fogarty International Center/NIMH. Ben Lacey acknowledges support from the NIHR Oxford Biomedical Research Centre and the BHF Centre of Research Excellence, Oxford. Ivan Landires is a member of the Sistema Nacional de InvestigaciA3n (SNI), which is supported by the Secretaria Nacional de Ciencia Tecnologia e Innovacion (SENACYT), Panama. Jeffrey V Lazarus acknowledges support by a Spanish Ministry of Science, Innovation and Universities Miguel Servet grant (Instituto de Salud Carlos III/ESF, European Union [CP18/00074]). Peter T N Memiah acknowledges CODESRIA; HISTP. Subas Neupane acknowledges partial support from the Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital. Shuhei Nomura acknowledges support from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (18K10082). Alberto Ortiz acknowledges support by ISCIII PI19/00815, DTS18/00032, ISCIII-RETIC REDinREN RD016/0009 Fondos FEDER, FRIAT, Comunidad de Madrid B2017/BMD-3686 CIFRA2-CM. These funding sources had no role in the writing of the manuscript or the decision to submit it for publication. George C Patton acknowledges support from a National Health & Medical Research Council Fellowship. Marina Pinheiro acknowledges support from FCT for funding through program DL 57/2016 -Norma transitA3ria. Alberto Raggi, David Sattin, and Silvia Schiavolin acknowledge support by a grant from the Italian Ministry of Health (Ricerca Corrente, Fondazione Istituto Neurologico C Besta, Linea 4 -Outcome Research: dagli Indicatori alle Raccomandazioni Cliniche). Daniel Cury Ribeiro acknowledges support from the Sir Charles Hercus Health Research Fellowship -Health Research Council of New Zealand (18/111). Perminder S Sachdev acknowledges funding from the NHMRC Australia. Abdallah M Samy acknowledges support from a fellowship from the Egyptian Fulbright Mission Program. Milena M Santric-Milicevic acknowledges support from the Ministry of Education, Science and Technological Development of the Republic of Serbia (Contract No. 175087). Rodrigo Sarmiento-Suarez acknowledges institutional support from University of Applied and Environmental Sciences in Bogota, Colombia, and Carlos III Institute of Health in Madrid, Spain. Maria Ines Schmidt acknowledges grants from the Foundation for the Support of Research of the State of Rio Grande do Sul (IATS and PrInt) and the Brazilian Ministry of Health. Sheikh Mohammed Shariful Islam acknowledges a fellowship from the National Heart Foundation of Australia and Deakin University. Aziz Sheikh acknowledges support from Health Data Research UK. Kenji Shibuya acknowledges Japan Ministry of Education, Culture, Sports, Science and Technology. Joan B Soriano acknowledges support by Centro de Investigacion en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Rafael Tabares-Seisdedos acknowledges partial support from grant PI17/00719 from ISCIII-FEDER. Santosh Kumar Tadakamadla acknowledges support from the National Health and Medical Research Council Early Career Fellowship, Australia. Marcello Tonelli acknowledges the David Freeze Chair in Health Services Research at the University of Calgary, AB, Canada., "Peer Reviewed"

Background The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality. Objectives The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of “at-risk” patient cohorts for failure to present or delays to treatment. Methods This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020. Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality. Results A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p, Central Illustration

Although a growing body of evidence suggests that colorectal cancer (CRC) is associated with alterations of fatty acid (FA) profiles in serum and tumor tissues, available data about polyunsaturated fatty acid (PUFA) content in CRC patients are inconclusive. Our study showed that CRC tissues contained more PUFAs than normal large intestinal mucosa. However, serum levels of PUFAs in CRC patients were lower than in healthy controls. To explain the mechanism of PUFA alterations in CRC, we measured FA uptake by the colon cancer cells and normal colon cells. The levels of PUFAs in colon cancer cell culture medium decreased significantly with incubation time, while no changes were observed in the medium in which normal colon cells were incubated. Our findings suggest that the alterations in tumor and serum PUFA profiles result from preferential uptake of these FAs by cancer cells; indeed, PUFAs are essential for formation of cell membrane phospholipids during rapid proliferation of cancer cells. This observation puts into question potential benefits of PUFA supplementation in CRC patients.