Attitudes of women towards products containing hormones (hormonal contraceptives or hormone therapy): what changes from pre to postmenopause?

IntroductionTo evaluate the actual perceptions of hormonal contraceptives (HC) in women of reproductive age in comparison with similar concerns of postmenopausal women in relation to hormone therapy (HT).Materials and methodsA questionnaire-based study was conducted in a population of 370 women, 198 (53.5%) premenopausal and 172 (46.5%) postmenopausal. Perceptions were evaluated using specific questions and Likert scales (-5 to +5).Multivariate regression analyses were adjusted for categories of HC/HT use (never, past and current).ResultsThe most reported adverse effect associated with hormonal treatments was venous thrombosis (1.4 ± 0.1), especially for HC use in premenopausal women (p < .0001). According to responses, hormonal treatments can increase the risk of developing venous thrombosis (OR 0.79; 95% CI 0.67–0.96, p = .004) and depression (OR 0.80; 95% CI 0.69–0.92, p = .002) more in pre-menopause, while they can increase the risk of weight gain more in post-menopause (OR 1.24: 95% CI 1.07–1.42, p = .003).The greatest oncological concern throughout life was about breast cancer (0.9 ± 0.1). There was the perception that hormonal treatments can increase the risk of developing ovarian cancer more in post-menopause (OR 1.44; 95% CI 1.19–1.75, p = .0002), while they can increase the risk of uterine cervix cancer more in pre-menopause (OR 0.74; 95% CI 0.52–0.97, p = .03).ConclusionsOur data suggest that our patients are primarily concerned about the effects of hormonal treatments on venous thrombosis, mood, breast cancer and cervical cancer risk, and, later in life, about their impact on weight gain, breast and ovarian cancer risk.

KEY MESSAGES

1. Young patients are primarily concerned about the effects of hormonal treatments on venous thrombosis, mood, breast cancer and cervical cancer risk.
2. Older patients are primarily concerned about the effects of hormonal treatments on weight gain, breast and ovarian cancer risk.
3. The greatest oncological concern throughout life was about breast cancer.

     

Comparison of the effects of general,spinal and epidural anesthesia on ureter access and surgical outcomes during flexible ureterorenoscopy for transurethral single stone removal surgeries: a monocentric retrospective study

BackgroundIn ureterorenoscopy, anaesthesiologists are preferring regional anaesthesia to avoid postoperative complications, while surgeons are preferring general anaesthesia to avoid ureteral trauma. China has not published its guidelines and not referring to the European Association of Urology guidelines. The objectives of study were to evaluate the effects of general, spinal, and epidural anaesthesia on ureter access and surgical outcomes of ureterorenoscopy.MethodsCharts of a total of 392 patients with the American Society of Anaesthesiologists grade I or II, and underwent flexible ureterorenoscopy for removal of the proximal, middle, or distal ureteral single stone under general anaesthesia (GA group; n = 145) or spinal anaesthesia (SA group; n = 131) or epidural anaesthesia (EA group; n = 116) were reviewed retrospectively.ResultsThe dilatation time for patients of GA group was fewer than those of SA (104.01 ± 12.77 sec/patient vs. 130.55 ± 22.53 sec/patient, p < .0001, q = 17.0350) and EA (104.01 ± 12.77 sec/patient vs. 147.03 ± 18.76 sec/patient, p < .0001, q = 26.7240) groups. The time to reach to stone for patients of GA group was fewer than those of SA (126.68 ± 12.59 sec/patient vs. 137.60 ± 17.84 sec/patient, p < .0001, q = 8.4510) and EA (126.68 ± 12.59 sec/patient vs. 149.44 ± 14.85 sec/patient, p < .0001, q = 17.0350) groups. The lithotripsy time (p = .359), operation time (p = .449), intraoperative complications (p = .058), and length of hospital stays (p = .057) of patients were same among groups. Visual analog scale pain scores of patients of the GA group found higher among groups. General anaesthesia caused nausea and vomiting.ConclusionsThis study suggests general anaesthesia for flexible ureterorenoscopy if there is no contraindication.

KEY MESSAGE

• General anaesthesia facilitates early dilatation of ureters and access to the stone.
• No strong correlation of the anaesthesia method of choice with lithotripsy time, operation time, intraoperative complications, stone-free conditions, and length of hospital stays.
• Epidural and spinal anaesthesia have advantages of fewer postoperative pain and better postoperative outcomes for flexible ureterorenoscopy.

     

Autoantibodies in association with subchorionic haematoma in early pregnancy

ObjectiveTo explore the possible aetiology of subchorionic haematoma (SCH), especially its association with autoantibodies.Material and methodsEarly pregnant women who were detected SCH through ultrasonography were identified as the study group and those without SCH at comparable ages who visited the clinic at the same period of time were compared as the control group. Indexes of laboratory immune tests were compared between the two groups, as well as their pregnancy outcomes.ResultsA total of 97 SCH patients and 130 control cases were recruited in this study. A higher proportion of women was detected autoantibodies in the SCH group compared with control group (45.36% vs 21.54%, p = .000). Positive rates of ANA (24.74% vs 10.77%, p = .005) and laboratory antiphospholipid antibodies (ACL, anti-β2 GP1 or LA) (25.77% vs 11.54%, p = .005) showed significant differences between the two groups. The incidence of vaginal bleeding was significantly higher in the SCH group (43.30% vs 20.00%, p = .000). While the miscarriage rates were not significantly different (17.53% vs 15.38%, p = .666). And there were no significant differences in terms of preterm delivery rate, caesarean section rate, birth weight and pregnancy complications. Most SCHs (96.25%) were absorbed before 20th gestational week. In the SCH group, the average birth weight was significantly lower in women with autoantibodies. Clinical features and other pregnancy outcomes showed no significant differences between SCH patients with and without autoantibodies.ConclusionsThe occurrence of SCH may be associated with autoantibodies. The pregnancy outcomes were comparable between women with and without SCH.

KEY MESSAGES

1. Subchorionic haematoma (SCH) is increasingly commonly observed in early pregnancy period, but the aetiology is uncertain and the clinical significance of SCH is controversial.
2. The occurrence of SCH may be associated with autoantibodies.
3. The pregnancy outcomes were not significantly different between women with and without SCH.

     

Neuromuscular sonography detects changes in muscle echotexture and nerve diameter in ICU patients within 24 h

PurposeDuring an ICU stay, changes in muscles and nerves occur that is accessible via neuromuscular sonography.Methods17 patients recruited from the neurological and neurosurgical ICU (six women; 66 ± 3 years) and 7 healthy controls (three women, 75 ± 3 years) were included. Muscle sonography (rectus abdominis, biceps, rectus femoris and tibialis anterior muscles) using gray-scale values (GSVs), and nerve ultrasound (peroneal, tibial and sural nerves) analyzing the cross-sectional area (CSA) were performed on days 1 (t1), 3 (t2), 5 (t3), 8 (t4), and 16 (t5) after admission.ResultsTime course analysis revealed that GSVs were significantly higher within the patient group for all of the investigated muscles (rectus abdominis: F = 7.536; p = 0.011; biceps: F = 14.761; p = 0.001; rectus femoris: F = 9.455; p = 0.005; tibialis anterior: F = 7.282; p = 0.012). The higher GSVs were already visible at t1 or, at the latest, at t2 (tibialis anterior muscles). CSA was enlarged in all of the investigated nerves in the patient group (peroneal nerve: F = 7.129; p = 0.014; tibial nerve: F = 28.976, p < 0.001; sural nerve: F = 13.051; p = 0.001). The changes were visible very early (tibial nerve: t1; peroneal nerve: t2). The CSA of the motor nerves showed an association with the ventilation time and days within the ICU (t1 through t4; p < 0.05).DiscussionWe detected very early changes in the muscles and nerves of ICU-patients. Nerve CSA might be a useful parameter to identify patients who are at risk for difficult weaning. Therefore our observations might be severity signs of neuromuscular suffering for the most severe patients.     

Safety and feasibility of the Woven EndoBridge device deployment with monitored anesthesia care

ObjectiveThe Woven EndoBridge (WEB) device can be used for complex intracranial aneurysms (IAs), mostly under general anesthesia (GA). However, it remains controversial if anesthetic management could affect procedural outcomes after endovascular treatments using the WEB for IAs. The purpose of this study is to investigate the safety and feasibility of the WEB deployment for patients under monitored anesthesia care (MAC).MethodsWe reviewed 27 IAs in 25 patients who were treated by using the WEB device from February to December in 2019. Our first-line anesthetic management of patients during the procedures was the MAC. GA was performed based on patient’s clinical status or preference. Subjects’ demographic data, aneurysms’ characteristics, procedure-related complications, grade of stasis after the WEB deployment, duration of procedure, and length of hospital stay were compared between subjects who underwent GA versus those who underwent MAC.ResultsSuccessful deployment of the WEB device was obtained in all patients. In total, 10 and 17 IAs were treated with GA and MAC, respectively. There was no significant difference in demographics (age: p = 0.12, sex: p = 0.54), aneurysms’ characteristics (ruptured: p = 1.00, neck width: p = 0.96, aspect ratio: p = 0.98, maximum diameter: p = 0.69), complications (p = 1.00), postprocedural grade of stasis (p = 1.00), duration of the procedure (p = 0.23), and the length of hospital stay (p = 0.81) between GA and MAC.ConclusionsMAC can be used for the WEB device deployment safely and effectively.     

Effectiveness of gonadotrophin-releasing hormone agonist therapy to improve the outcomes of intrauterine insemination in patients suffering from stage I-II endometriosis

ObjectiveTo explore the role of postoperative gonadotrophin releasing hormone agonist (GnRH-a) therapy before treatment with intrauterine insemination (IUI) for infertile females with stage I-II endometriosis.Material and methodsNinety-seven patients diagnosed with stage I-II endometriosis before IUI were enrolled in this study. The clinical pregnancy rate, cumulative pregnancy rate, live birth rate and newborn conditions were compared between the two groups with and without GnRH-a therapy.ResultsThe clinical pregnancy rate of IUI in the GnRH-a group was higher than that in the control group (15.29% vs. 11.82%, p = .035). By logistic regression analysis, patients treated with GnRH-a had a higher clinical pregnancy rate than those without (adjusted odds ratio (AOR) 23.190, 95% confidence interval (CI) 1.238–434.312). The live birth rate per IUI cycle in the GnRH-a group was also higher than in the controls (12.94% vs. 10%). However, the difference was not statistically significant (p = .311, AOR 4.844, 95% CI 0.229–102.320). The patients with GnRH-a therapy had a similar incidence of multiple pregnancy rate (0% vs. 0%), miscarriage rate (2.35% vs. 0.91%) and ectopic pregnancy rate (0% vs. 0.91%) as compared to the control group. The cumulative pregnancy rates were all higher in patients administered with GnRH-a than those without GnRH-a treatment in different cycles (one cycle: 17.07% vs 12.50%; two cycles: 29.27% vs 19.64%; three cycles: 31.71% vs 23.21%; ≥four cycles: 31.71% vs 23.21%), but the difference was not statistically significant. Notably, there was no more pregnancy after the third IUI cycle. The gestation weeks of delivery in the two groups were 39.09 ± 1.04 and 38.60 ± 1.17, respectively (p = .323). Nor was there difference in birth weight between the two groups (3236 ± 537 g vs 3435 ± 418 g, p = .360).ConclusionsThe administration of GnRH-a in patients with stage I-II endometriosis could be beneficial to the outcomes of IUI. It is recommended that IUI should be discontinued after three failed attempts.

KEY MESSAGES

1. Endometriosis is a common cause of infertility, but the exact mechanism remains unclear.
2. The administration of GnRH-a before IUI treatment is beneficial for patients suffering from stage I-II endometriosis.
3. After three failed attempts, IUI should be stopped in patients with stage I-II endometriosis.

     

Association of immune-related adverse events induced by nivolumab with a battery of autoantibodies

BackgroundThe aim of this study was to assess the diagnostic performance of an autoantibody battery in patients receiving immune checkpoint inhibitors who experienced immune-related adverse events (irAEs).MethodsWe retrospectively analyzed several variables potentially related to irAEs, namely, demographic, clinical, and laboratory characteristics, including an autoantibody battery (antinuclear, anti-neutrophil cytoplasmic, anti-thyroid antibodies and rheumatoid factor).ResultsSixty-nine patients (48 men; 61.8 ± 10.9 years at baseline) diagnosed with stage-4 solid-organ cancer and treated with nivolumab were followed up for 12 ± 10.3 months. Thirty-two irAEs were detected in 26 patients (37.5%). Adverse events occurred more commonly in women (62% vs. 27%, p = .006), and younger patients (irAEs: 58.1 ± 9.8, no irAEs: 64.1 ± 10.9 years, p = .024). Autoantibody battery results were available for 26 patients and were more frequently positive in patients with irAEs (87% vs. 30%, p = .009). The positive predictive value, negative predictive value, and diagnostic accuracy of the battery were 82.3%, 77.8%, and 80.8%, respectively. Among the 64 patients with an evaluable response, 23 (38.5%) experienced tumour progression, this being less frequent in patients with irAEs (19% vs. 48.5%, p = .03). Overall survival was higher in patients developing irAEs (HR = 1.88, p = .05).ConclusionPositivity in a readily available autoantibody battery may be associated with the occurrence of irAEs.

KEY MESSAGES

• Positivity in an accessible and inexpensive autoantibody battery including antinuclear, anti-neutrophil cytoplasmic, anti-thyroid antibodies and rheumatoid factor may be associated with the occurrence of immune-related adverse events.
• Patients with cancer on immune checkpoint inhibitors experiencing immune-related adverse events showed a lower risk of progression and better overall survival than patients not experiencing this type of adverse effect.

     

Eupalinilide B as a novel anti-cancer agent that inhibits proliferation and epithelial–mesenchymal transition in laryngeal cancer cells

ObjectiveTo investigate the anti-cancer effects and potential mechanisms of eupalinilide B in laryngeal cancer cells.MethodsLaryngeal cancer cell lines were selected to study the anti-tumor effects of eupalinilide B in vitro and in vivo. Lysine-specific demethylase 1 (LSD1) activity was assessed in vitro and dialysis experiments were performed to identify the anti-tumor target of the drug.ResultsEupalinilide B concentration-dependently inhibited the proliferation of laryngeal cancer cells, exhibiting potent inhibitory activity against TU686 (IC₅₀ = 6.73 µM), TU212 (IC₅₀ = 1.03 µM), M4e (IC₅₀ = 3.12 µM), AMC-HN-8 (IC₅₀ = 2.13 µM), Hep-2 (IC₅₀ = 9.07 µM), and LCC cells (IC₅₀ = 4.20 µM). Subsequent target verification experiments demonstrated that eupalinilide B selectively and reversibly inhibited LSD1. Furthermore, eupalinilide B, as a natural product, suppressed epithelial–mesenchymal transition in TU212 cells. An in vivo experiment further indicated that eupalinilide B could significantly reduce the growth of tumors in TU212 xenograft mouse models.ConclusionsEupalinilide B might be a novel LSD1 inhibitor for treating laryngeal cancer.     

Comparison of pregnenolone sulfate,pregnanolone and estradiol levels between patients with menstrually-related migraine and controls: an exploratory study

BackgroundNeurosteroids affect the balance between neuroexcitation and neuroinhibition but have been little studied in migraine. We compared the serum levels of pregnenolone sulfate, pregnanolone and estradiol in women with menstrually-related migraine and controls and analysed if a correlation existed between the levels of the three hormones and history of migraine and age.MethodsThirty women (mean age ± SD: 33.5 ± 7.1) with menstrually-related migraine (MM group) and 30 aged- matched controls (mean age ± SD: 30.9 ± 7.9) participated in the exploratory study. Pregnenolone sulfate and pregnanolone serum levels were analysed by liquid chromatography-tandem mass spectrometry, while estradiol levels by enzyme-linked immunosorbent assay.ResultsSerum levels of pregnenolone sulfate and pregnanolone were significantly lower in the MM group than in controls (pregnenolone sulfate: P = 0.0328; pregnanolone: P = 0.0271, Student’s t-test), while estradiol levels were similar. In MM group, pregnenolone sulfate serum levels were negatively correlated with history of migraine (R² = 0.1369; P = 0.0482) and age (R² = 0.2826, P = 0.0025) while pregnenolone sulfate levels were not age-related in the control group (R² = 0.04436, P = 0.4337, linear regression analysis).ConclusionLow levels of both pregnanolone, a positive allosteric modulator of the GABAA receptor, and pregnenolone sulfate, a positive allosteric modulator of the NMDA receptor, involved in memory and learning, could contribute either to headache pain or the cognitive dysfunctions reported in migraine patients. Overall, our results agree with the hypothesis that migraine is a disorder associated with a loss of neurohormonal integrity, thus supporting the therapeutic potential of restoring low neurosteroid levels in migraine treatment.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01231-9.     

Some characteristics of hyperglycaemic crisis differ between patients with and without COVID-19 at a safety-net hospital in a cross-sectional study

ObjectiveTo compare patients with DKA, hyperglycaemic hyperosmolar syndrome (HHS), or mixed DKA-HHS and COVID-19 [COVID (+)] to COVID-19-negative (−) [COVID (−)] patients with DKA/HHS from a low-income, racially/ethnically diverse catchment area.MethodsA cross-sectional study was conducted with patients admitted to an urban academic medical center between 1 March and 30 July 2020. Eligible patients met lab criteria for either DKA or HHS. Mixed DKA-HHS was defined as meeting all criteria for either DKA or HHS with at least 1 criterion for the other diagnosis.ResultsA total of 82 participants were stratified by COVID-19 status and type of hyperglycaemic crisis [26 COVID (+) and 56 COVID (−)]. A majority were either Black or Hispanic. Compared with COVID (−) patients, COVID (+) patients were older, more Hispanic and more likely to have type 2 diabetes (T2D, 73% vs 48%, p < .01). COVID(+) patients had a higher mean pH (7.25 ± 0.10 vs 7.16 ± 0.16, p < .01) and lower anion gap (18.7 ± 5.7 vs 22.7 ± 6.9, p = .01) than COVID (−) patients. COVID (+) patients were given less intravenous fluids in the first 24 h (2.8 ± 1.9 vs 4.2 ± 2.4 L, p = .01) and were more likely to receive glucocorticoids (95% vs. 11%, p < .01). COVID (+) patients may have taken longer to resolve their hyperglycaemic crisis (53.3 ± 64.8 vs 28.8 ± 27.5 h, p = .09) and may have experienced more hypoglycaemia <3.9 mmol/L (35% vs 19%, p = .09). COVID (+) patients had a higher length of hospital stay (LOS, 14.8 ± 14.9 vs 6.5 ± 6.0 days, p = .01) and in-hospital mortality (27% vs 7%, p = .02).DiscussionCompared with COVID (−) patients, COVID (+) patients with DKA/HHS are more likely to have T2D. Despite less severe metabolic acidosis, COVID (+) patients may require more time to resolve the hyperglycaemic crisis and experience more hypoglycaemia while suffering greater LOS and risk of mortality. Larger studies are needed to examine whether differences in management between COVID (+) and (−) patients affect outcomes with DKA/HHS.     

Intracranial pressure directly predicts headache morbidity in idiopathic intracranial hypertension

ObjectiveHeadache is the predominant disabler in idiopathic intracranial hypertension (IIH). The aim was to characterise headache and investigate the association with intracranial pressure.MethodsIIH:WT was a randomised controlled parallel group multicentre trial in the United Kingdom investigating weight management methods in IIH. Participants with active IIH (evidenced by papilloedema) and a body mass index (BMI) ≥35 kg/m² were recruited. At baseline, 12 months and 24 months headache characteristics and quality of life outcome measures were collected and lumbar puncture measurements were performed.ResultsSixty-six women with active IIH were included with a mean age of 32.0 years (SD ± 7.8), and mean body mass index of 43.9 ± 7.0 kg/m². The headache phenotype was migraine-like in 90%. Headache severity correlated with ICP at baseline (r = 0.285; p = 0.024); change in headache severity and monthly headache days correlated with change in ICP at 12 months (r = 0.454, p = 0.001 and r = 0.419, p = 0.002 respectively). Cutaneous allodynia was significantly correlated with ICP at 12 months. (r = 0.479, p < 0.001). Boot strap analysis noted a positive association between ICP at 12 and 24 months and enabled prediction of both change in headache severity and monthly headache days. ICP was associated with significant improvements in quality of life (SF-36).ConclusionsWe demonstrate a positive relationship between ICP and headache and cutaneous allodynia, which has not been previously reported in IIH. Those with the greatest reduction in ICP over 12 months had the greatest reduction in headache frequency and severity; this was associated with improvement of quality of life measures.Trial registrationThis work provides Class IIa evidence of the association of raised intracranial pressure and headache. ClinicalTrials.gov number, {"type":"clinical-trial","attrs":{"text":"NCT02124486","term_id":"NCT02124486"}}NCT02124486.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01321-8.     

Cluster Headache Impact Questionnaire (CHIQ) – a short measure of cluster headache related disability

BackgroundCluster headache (CH) is a severe, highly disabling primary headache disorder. However, there is little research on CH-related disability, and most of it is based on non CH-specific questionnaires. The aim of this study was to develop a short, CH-specific disability questionnaire.MethodsThe 8-item Cluster Headache Impact Questionnaire (CHIQ) was developed based on a literature review and patient and expert interviews. The questionnaire was tested in 254 CH patients (171 males; 47.5 ± 11.4 years; 111 chronic CH, 85 active episodic CH, 52 episodic CH in remission) from our tertiary headache center or from a German support group.ResultsReliability and validity of the CHIQ was evaluated in active episodic and chronic CH patients (n = 196). Internal consistency (Cronbach’s α = 0.88) and test-retest reliability (ICC 0.91, n = 41) were good. Factor analysis identified a single factor. Convergent validity was shown by significant correlations with the Headache Impact Test (HIT-6, r = 0.58, p < 0.001), subscales of the depression, anxiety and stress scales (DASS, r = 0.46–0.62; p < 0.001) and with CH attack frequency (r = 0.41; p < 0.001). CHIQ scores significantly differentiated between chronic CH (25.8 ± 6.5), active episodic CH (23.3 ± 6.9) and episodic CH patients in remission (13.6 ± 11.9, p < 0.05 for all 3 comparisons).ConclusionsThe CHIQ is a short, reliable, valid, and easy to administer measure of CH-related disability, which makes it a useful tool for clinical use and research.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01406-y.     

Performance and user evaluation of a novel capacitance-based automatic urinometer compared with a manual standard urinometer after elective cardiac surgery

IntroductionIn the intensive care setting, most physiologic parameters are monitored automatically. However, urine output (UO) is still monitored hourly by manually handled urinometers. In this study, we evaluated an automatic urinometer (AU) and compared it with a manual urinometer (MU).MethodsThis prospective study was carried out in the intensive care unit of a cardiothoracic surgical clinic. In postoperative patients (n = 34) with indwelling urinary catheters and an expected stay of 24 hours or more, hourly UO samples were measured with an AU (Sippi, n = 220; Observe Medical, Gothenburg, Sweden) or an MU (UnoMeter™ 500, n = 188; Unomedical, Birkerød, Denmark) and thereafter validated by cylinder measurements. Malposition of the instrument at the time of reading excluded measurement. Data were analyzed with the Bland-Altman method. The performance of the MU was used as the minimum criterion of acceptance when the AU was evaluated. The loss of precision with the MU due to temporal deviation from fixed hourly measurements was recorded (n = 108). A questionnaire filled out by the ward staff (n = 28) was used to evaluate the ease of use of the AU compared with the MU.ResultsBland-Altman analysis showed a smaller mean bias for the AU (+1.9 ml) compared with the MU (+5.3 ml) (P <0.0001). There was no statistical difference in measurement precision between the two urinometers, as defined by their limits of agreement (±15.2 ml vs. ±16.6 ml, P = 0.11). The mean temporal variation with the MU was ±7.4 minutes (±12.4%), and the limits of agreement were ±23.9 minutes (±39.8%), compared with no temporal variation with the AU (P <0.0001). The ward staff considered the AU easy to learn to use and rated it higher than the MU (P <0.0001).ConclusionsThe AU was not inferior to the MU and was significantly better in terms of bias, temporal deviation and staff opinion, although the clinical relevance of these findings may be open to discussion.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-0899-4) contains supplementary material, which is available to authorized users.     

Clinical symptoms of androgen deficiency in men with migraine or cluster headache: a cross-sectional cohort study

BackgroundTo compare symptoms of clinical androgen deficiency between men with migraine, men with cluster headache and non-headache male controls.MethodsWe performed a cross-sectional study using two validated questionnaires to assess symptoms of androgen deficiency in males with migraine, cluster headache, and non-headache controls. Primary outcome was the mean difference in androgen deficiency scores. Generalized linear models were used adjusting for age, BMI, smoking and lifetime depression. As secondary outcome we assessed the percentage of patients reporting to score below average on four sexual symptoms (beard growth, morning erections, libido and sexual potency) as these items were previously shown to more specifically differentiate androgen deficiency symptoms from (comorbid) anxiety and depression.ResultsThe questionnaires were completed by n = 534/853 (63%) men with migraine, n = 437/694 (63%) men with cluster headache and n = 152/209 (73%) controls. Responders were older compared to non-responders and more likely to suffer from lifetime depression.Patients reported more severe symptoms of clinical androgen deficiency compared with controls, with higher AMS scores (Aging Males Symptoms; mean difference ± SE: migraine 5.44 ± 0.90, p <  0.001; cluster headache 5.62 ± 0.99, p <  0.001) and lower qADAM scores (quantitative Androgen Deficiency in the Aging Male; migraine: − 3.16 ± 0.50, p <  0.001; cluster headache: − 5.25 ± 0.56, p <  0.001). Additionally, both patient groups more often reported to suffer from any of the specific sexual symptoms compared to controls (18.4% migraine, 20.6% cluster headache, 7.2% controls, p = 0.001).ConclusionMen with migraine and cluster headache more often suffer from symptoms consistent with clinical androgen deficiency than males without a primary headache disorder.     

Mildly elevated thyroid-stimulating hormone is associated with endothelial dysfunction and severe preeclampsia among pregnant women with insufficient iodine intake in Eastern Cape province,South Africa

BackgroundPreeclampsia and hypothyroidism are associated with endothelial dysfunction. Iodine deficiency is a risk factor for subclinical hypothyroidism in pregnancy. However, there is a paucity of data on the relationship between iodine nutrition state in pregnancy, the degree of endothelial dysfunction, and the risk of preeclampsia.MethodsNinety-five normotensive pregnant women, 50 women with preeclampsia with no severe features, and 50 women with severe preeclampsia were enrolled into the current study from the maternity units of Nelson Mandela Academic Hospital and Mthatha Regional Hospitals in Eastern Cape Province, South Africa. Urinary iodine concentration (UIC), serum markers of thyroid function, aortic augmentation index, and pulse wave velocity (PWV) were compared.ResultsMedian UIC was 167.5, 127.7, and 88.5 µg/L, respectively for normotensive pregnant women, those with preeclampsia and severe preeclampsia (p = .150). Participants with severe preeclampsia had significantly higher median thyroid-stimulating hormone (TSH) and oxidized LDL than normotensive and preeclamptic women without severe features (respectively 3.0, 2.3, and 2.3 IU/L; 1.2, 1.0, and 1.0 IU/L, p < .05). The median Aortic augmentation index was 7.5, 19.0, and 21.0 (p < .001), and the pulse wave velocity 5.1, 5.7, and 6.3, respectively for normotensive, preeclampsia, and severe preeclampsia participants (both p < .001). In linear regressions, TSH, age, and hypertensive disease were independent predictors of elevated PWV.ConclusionUpper normal-range TSH levels in women with severe preeclampsia were associated with markers of endothelial dysfunction. The low UIC and trend towards the elevation of thyroglobulin suggest that inadequate iodine intake may have increased TSH levels and indirectly caused endothelial dysfunction.     

Single-Pulse Transcranial Magnetic Stimulation for the preventive treatment of difficult-to-treat migraine: a 12-month prospective analysis

BackgroundInitial evidence have shown the short-term efficacy of sTMS in the acute and preventive treatment of migraine. It is unknown whether this treatment approach in the long-term is effective and well tolerated in difficult-to-treat migraine.MethodsThis is a prospective, single centre, open-label, real-world analysis conducted in difficult-to-treat patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM) with and without medication overuse headache (MOH), who were exposed to sTMS therapy. Patients responding to a three-month sTMS treatment, continued the treatment and were assessed again at month 12. The cut-off outcome for treatment continuation was reduction in the monthly moderate to severe headache days (MHD) of at least 30% (headache frequency responders) and/or a ≥ 4-point reduction in headache disability using the Headache Impact test-6 (HIT-6) (headache disability responders).ResultsOne hundred fifty-three patients were included in the analysis (F:M = 126:27, median age 43, IQR 32.3–56.8). At month 3, 93 out of 153 patients (60%) were responders to treatment. Compared to baseline, the median reduction in monthly headache days (MHD) for all patients at month 3 was 5.0 days, from 18.0 (IQR: 12.0–26.0) to 13.0 days (IQR: 5.75–24.0) (P = 0.002, r = − 0.29) and the median reduction in monthly migraine days (MMD) was 4.0 days, from 13.0 (IQR: 8.75–22.0) to 9.0 (IQR: 4.0–15.25) (P = 0.002, r = − 0.29). Sixty-nine out of 153 patients (45%) reported a sustained response to sTMS treatment at month 12. The percentage of patients with MOH was reduced from 52% (N = 79/153) at baseline to 19% (N = 29/153) at month 3, to 8% (N = 7/87) at month 12. There was an overall median 4-point reduction in HIT-6 score, from 66 (IQR: 64–69) at baseline to 62 at month 3 (IQR: 56–65) (P < 0.001, r = − 0.51). A total of 35 mild/moderate adverse events were reported by 23 patients (15%). One patient stopped sTMS treatment due to scalp sensitivity.ConclusionsThis open label analysis suggests that sTMS may be an effective, well-tolerated treatment option for the long-term prevention of difficult-to-treat CM and HFEM.     

Automatic geographic atrophy segmentation using optical attenuation in OCT scans with deep learning

A deep learning algorithm was developed to automatically identify, segment, and quantify geographic atrophy (GA) based on optical attenuation coefficients (OACs) calculated from optical coherence tomography (OCT) datasets. Normal eyes and eyes with GA secondary to age-related macular degeneration were imaged with swept-source OCT using 6 × 6 mm scanning patterns. OACs calculated from OCT scans were used to generate customized composite en face OAC images. GA lesions were identified and measured using customized en face sub-retinal pigment epithelium (subRPE) OCT images. Two deep learning models with the same U-Net architecture were trained using OAC images and subRPE OCT images. Model performance was evaluated using DICE similarity coefficients (DSCs). The GA areas were calculated and compared with manual segmentations using Pearson’s correlation and Bland-Altman plots. In total, 80 GA eyes and 60 normal eyes were included in this study, out of which, 16 GA eyes and 12 normal eyes were used to test the models. Both models identified GA with 100% sensitivity and specificity on the subject level. With the GA eyes, the model trained with OAC images achieved significantly higher DSCs, stronger correlation to manual results and smaller mean bias than the model trained with subRPE OCT images (0.940 ± 0.032 vs 0.889 ± 0.056, p = 0.03, paired t-test, r = 0.995 vs r = 0.959, mean bias = 0.011 mm vs mean bias = 0.117 mm). In summary, the proposed deep learning model using composite OAC images effectively and accurately identified, segmented, and quantified GA using OCT scans.     

Circulating long non‐coding RNA Coromarker expression correlated with inflammation,coronary artery stenosis,and plaque vulnerability in patients with coronary artery disease

BackgroundThe aim of the study was to assess the correlation between circulating long non‐coding RNA (lncRNA) OTTHUMT00000387022 (named Coromarker) expression and disease severity, inflammatory cytokine levels, and plaque vulnerability in patients with coronary artery disease (CAD).MethodsA total of 134 participants who received coronary angiography were enrolled and classified them as CAD patients (N = 89) and controls (N = 45). Blood samples were obtained from all subjects. Quantitative polymerase chain reaction was used to evaluate Coromarker expression. The enzyme‐linked immunosorbent test was used to measure inflammatory cytokines including high sensitivity C reactive protein (hsCRP), interleukin (IL)‐1β (IL‐1β), IL‐6, NOD‐like receptor protein 3 (NLRP3), and markers of coronary plaque stability including matrix metallopeptidase 9 (MMP‐9) and soluble CD40 ligand (sCD40L). The severity of coronary stenosis was determined from the Gensini Score.ResultsLncRNA Coromarker expression was elevated to a greater extent in CAD patients than in control subjects before and after adjustments for age/gender (both p < 0.001); it was an independent predictor of CAD risk (area under curve: 0.824, 95% CI: 0.732–0.915). Additionally, Coromarker expression was significantly associated with Gensini Score (r = 0.574, p < 0.001), hsCRP (r = 0.221, p = 0.015), IL‐1β (r = 0.351, p < 0.001), IL‐6 (r = 0.286, p < 0.01), and NLRP3 levels (r = 0.312, p < 0.001). Coromarker expression was found to be linked with MMP‐9 (r = 0.260, p < 0.01) and sCD40L (r = 0.441, p < 0.001).ConclusionCirculating lncRNA Coromarker expression correlates with increased disease severity and inflammation as well as plaque vulnerability in patients with CAD.     

Performance evaluation of presepsin using a Sysmex HISCL‐5000 analyzer and determination of reference interval

BackgroundAnalytical evaluation of newly developed presepsin by a Sysmex HISCL‐5000 (Sysmex, Japan) automated immune analyzer was performed.MethodsFor evaluation, sepsis patient samples were collected before treatment in an emergency department. Precision, linearity, limit of blank/limit of detection, method comparisons, and reference intervals were evaluated. Method comparisons were performed using a PATHFAST immune analyzer (LSI Medience Corporation, Japan).ResultsPrecision using a 20x2x2 protocol for low (306 pg/mL) and high (1031 pg/mL) levels resulted in within‐laboratory standard deviation (95% confidence interval [CI]) and coefficient of variation (CV) %, which were as follows: 15.3 (13.1–18.7), 5.5% and 47.7, (40.5–58.1), 6.4%, respectively. Linearity using patient samples and calibrators were measured from 201 to 16,177 and 188 to 30,000 pg/mL, respectively. The regression equation was y = −23.2 + 1.008x (SE = 162.4) for low levels and y = 779.9 + 1.006x (SE = 668) for high levels. Method comparison by Passing–Bablock analysis was as follows: y = −209.77 + 1.047x (S_yx = 335.3). The correlation coefficient (95% CI) was 0.869 (0.772–0.927) with statistical significance (p < 0.001). Reference intervals from 120 normal healthy subjects showed that 300 pg/mL was the cut off. Presepsin tended to show a higher value at higher ages and in males. Presepsin showed correlation with some parameters, and the correlation coefficient (p value) were as follows: hematocrit, 0.198 (0.03); eGFR (CKD‐EPI), −0.240 (0.0129); MDRD‐eGFR, −0.194 (0.048), respectively.ConclusionPresepsin measurement by HISCL‐5000 showed reliable performance. Further clinical studies are required for the diagnosis and prognosis of sepsis.