Negative associations between maternal prenatal hair cortisol and child socioemotional problems.

Maternal prenatal distress can participate in the programming of offspring development, in which exposure to altered maternal long-term cortisol levels as measured by hair cortisol concentrations (HCC) may contribute. Yet, studies investigating whether and how maternal prenatal HCC associates with problems in child socioemotional development are scarce. Furthermore, questions remain regarding the timing and potential sex-specificity of fetal exposure to altered cortisol levels and whether there are interactions with maternal prenatal distress, such as depressive symptoms. The subjects were drawn from those FinnBrain Birth Cohort families that had maternal reports of child socioemotional problems (the Brief Infant-Toddler Social and Emotional Assessment [BITSEA] at 2 years and/or the Strengths and Difficulties Questionnaire [SDQ] at 5 years) as follows: HCC1 population: maternal mid-pregnancy HCC measured at gestational week 24 with 5 cm segments to depict cortisol levels from the previous five months (n = 321); and HCC2 population: end-of-pregnancy HCC measured 1-3 days after childbirth (5 cm segment; n = 121). Stepwise regression models were utilized in the main analyses and a sensitivity analysis was performed to detect potential biases. Negative associations were observed between maternal HCC2 and child BITSEA Total Problems at 2 years but not with SDQ Total difficulties at 5 years, and neither problem score was associated with HCC1. In descriptive analyses, HCC2 was negatively associated with Internalizing problems at 2 years and SDQ Emotional problems at 5 years. A negative association was observed among 5-year-old girls between maternal HCC1 and SDQ Total Difficulties and the subscales of Conduct and Hyperactivity/inattentive problems. When interactions were also considered, inverse associations between HCC2 and BITSEA Internalizing and Dysregulation Problems were observed in subjects with elevated prenatal depressive symptoms. It was somewhat surprising that only negative associations were observed between maternal HCC and child socioemotional problems. However, there are previous observations of elevated end-of-pregnancy cortisol levels associating with better developmental outcomes. The magnitudes of the observed associations were, as expected, mainly modest. Future studies with a focus on the individual changes of maternal cortisol levels throughout pregnancy as well as studies assessing both maternal and child HPA axis functioning together with child socioemotional development are indicated.

Hair cortisol, cortisone and DHEA concentrations and the composition of microbiota in toddlers.

Animal research suggests that the gut microbiota and the HPA axis communicate in a bidirectional manner. However, human data, especially on early childhood, remain limited. In this exploratory design, we investigated the connections between long-term HPA axis functioning, measured as cortisol, cortisone or dehydroepiandrosterone concentrations and their ratios from hair segments of three centimeters, and gut microbiota profiles, (measured as diversity and bacterial composition by 16 S rRNA sequencing) in healthy 2.5-year-old toddlers (n = 135) recruited from the FinnBrain Birth Cohort Study. The alpha diversity of the microbiota was studied by linear regression. Beta diversity analyses with weighted UniFrac or Bray-Curtis distances were performed using PERMANOVA. The bacterial core genus level analyses were conducted using DESeq2 and ALDEx2. These analyses suggested that hair sample concentrations of separate hormones, cortisol/cortisone and cortisol/dehydroepiandrosterone ratios were associated with various gut bacterial genera such as the Veillonella, the [Ruminococcus] torques group and [Eubacterium] hallii group, although multiple testing correction attenuated the p-values. Alpha or beta diversity was not linked with either steroid concentrations or ratios. These findings in toddlers suggest that long-term HPA axis activity may be related to genera abundancies but not to ecosystem-level measures in gut microbiota. The influence of these observed interrelations on later child health and development warrants further research.

Hair Cortisol Concentrations Are Associated with Dental Anxiety during Pregnancy.

Dental anxiety (DA) and hair cortisol concentrations (HCC) are associated with psychological symptoms and vary during pregnancy. We aimed to examine the association between HCC and DA at two points of pregnancy. Participants were pregnant mothers (n = 533) drawn from the FinnBrain Birth Cohort Study donating a hair sample at gestational week (gwk) 24 (n = 442) and/or at delivery (n = 176) and completed questionnaires on DA. Two groups, HCC1 and HCC2, treated as separate in the analyses, were formed according to the hair sample donation time i.e., gwk24 and delivery. 85 subjects were included in both groups. MDAS, EPDS, and SCL-90 were used to measure DA, depressive and anxiety symptoms, respectively, at gwk14 for the HCC1 group and gwk34 for the HCC2 group. The association between DA and HCC was studied with a binary logistic regression model, adjusted for anxiety and depressive symptoms, age, BMI, and smoking status. Individuals with high DA had lower HCC levels at gwk24 (OR = 0.548; 95% CI = 0.35-0.86; p = 0.009), but the association was not statistically significant at the delivery (OR = 0.611; 95% CI = 0.28-1.33; p = 0.216). The independent association between HCC and DA in pregnant women suggests that long-term cortisol levels could play a role in the endogenous etiology of DA. Further studies are however, needed.

Maternal prenatal psychological distress and hair cortisol levels associate with infant fecal microbiota composition at 2.5 months of age.

BACKGROUND: Maternal prenatal stress associates with infant developmental outcomes, but the mechanisms underlying this association are not fully understood. Alterations in the composition and function of infant intestinal microbiota may mediate some of the observed health effects, a viewpoint that is supported by animal studies along with a small human study showing that exposure to prenatal stress modifies the offspring's intestinal microbiota. In the current study, we aim to investigate the associations between maternal prenatal psychological distress (PPD) and hair cortisol concentration (HCC) with infant fecal microbiota composition in a large prospective human cohort. METHODS: The study population was drawn from FinnBrain Birth Cohort Study. Maternal PPD was measured with standardized questionnaires (EPDS, SCL, PRAQ-R2, Daily Hassles) three times during pregnancy (n = 398). A measure addressing the chronicity of PPD was composed separately for each questionnaire. HCC was measured from a five cm segment at gestational week 24 (n = 115), thus covering the early and mid-pregnancy. Infant fecal samples were collected at the age of 2.5 months and analyzed with 16S rRNA amplicon sequencing. RESULTS: Maternal chronic PPD (all symptom measures) showed positive associations (FDR < 0.01) with bacterial genera from phylum Proteobacteria, with potential pathogens, in infants. Further, chronic PPD (SCL, PRAQ-R2, and Daily Hassles negative scale) associated negatively with Akkermansia. HCC associated negatively with Lactobacillus. Neither maternal chronic PPD nor HCC associated with infant fecal microbiota diversity. CONCLUSION: Chronic maternal PPD symptoms and elevated HCC associate with alterations in infant intestinal microbiota composition. In keeping with the earlier literature, maternal PPD symptoms were associated with increases in genera fromProteobacteria phylum. Further research is needed to understand how these microbiota changes are linked with later child health outcomes.

Alexithymic Traits and Hair Cortisol Concentrations in Pregnant Women.

INTRODUCTION: Alexithymia, a personality construct characterized by difficulties in identifying and expressing emotions, and an externally oriented thinking style, has been associated with a number of stress-related disorders, and physiological markers of stress. We examined the relationships of alexithymia and hair cortisol concentrations (HCC), a measure of long-term cortisol levels, in pregnant women. METHODS: Participants were 130 women from the FinnBrain Birth Cohort study. Alexithymia was measured with the Toronto Alexithymia Scale (TAS-20). Analysis of covariance and regression analyses were used to assess the associations between alexithymia and HCC. Educational level, current depressive symptoms, and body mass index (BMI) were applied as covariates. RESULTS: In the adjusted analyses, individuals with moderate to high alexithymic traits had significantly higher HCC (F = 5.11, partial η² = 0.040 , p = 0.026) compared to non-alexithymics. Regression analyses in the whole sample revealed that, of the individual dimensions of alexithymia, Difficulty Identifying Feelings (DIF) was associated with HCC (ß = 0.187, t = 2.064, p = 0.041). CONCLUSIONS: Alexithymia, and especially its dimension DIF, were associated with higher HCC and, therefore, may be linked to increased chronic physiological stress. Implications for pregnancy outcomes and infant development are discussed.

Maternal prenatal hair cortisol is associated with prenatal depressive symptom trajectories.

Maternal prenatal cortisol levels have been inconsistently associated with self-reports of prenatal psychological distress (PD). Previous research has linked hair cortisol concentration (HCC) evaluating cumulatively the previous months with cross-sectional PD measures that usually cover the past week(s), which may lead to misleading conclusions on their relations. We aimed to investigate how maternal HCC relates to cumulative PD measures across pregnancy. METHODS: Subjects (N = 595) were drawn from the FinnBrain Birth Cohort Study. Maternal HCC was measured from hair samples collected at gestational week (gwk) 24 (HCC1, n = 467) and at delivery (HCC2, n = 222). As HCC1 and HCC2 comprised mostly of different subjects, they were considered as independent populations. Maternal PD assessments at gwks 14, 24, and 34 were the Edinburgh Postnatal Depression Scale (EPDS), the anxiety subscale of the Symptom Checklist (SCL-90), the Pregnancy-Related Anxiety Questionnaire -Revised2 (PRAQ-R2), and a daily hassles scale. Cumulative PD comprised of the mean scores of two consecutive assessments (mean1 = gwks 14 and 24; mean2 = gwks 24 and 34). In addition, EPDS and SCL scores were modelled by using growth mixture modelling to identify symptom trajectory categories. Regression models were adjusted for age, body mass index, education and use of selective serotonin/serotonin-norepinephrine reuptake inhibitor medication. RESULTS: In the adjusted regression model, higher HCC2 was related to the "consistently elevated" prenatal depressive symptoms trajectory in comparison to "consistently low" (ß =.71, p =.021) and "low and increasing" (ß =.82, p = .011) symptom trajectories. Additionally, the cumulative mean (mean 1) of daily hassles in relationships was associated with HCC1 (ß = 0.25, p = .004). General or pregnancy-related anxiety symptoms were unrelated to HCC after adjustment for the covariates. CONCLUSIONS: The assessment of cumulative or trajectory measures of PD can reveal important associations with maternal prenatal HCC, even though the associations are generally weak. Of the different dimensions of PD, prenatal trajectories of depressive symptoms were most consistently linked with end-pregnancy HCC levels.

Modified internal mammary artery perforator flap in treatment of sternal wound complications.

OBJECTIVES: There are multiple treatment strategies and flap options to cover defects after deep sternal wound infections and other similar sternal defects. The choice of flap is made according to surgeons' preferences and the size and location of the defect. Our aim is to introduce a new option to cover these kinds of defects with an internal mammary artery perforator flap combined with a pectoralis major muscle flap mostly raised with a muscle-sparing technique. DESIGN: We treated 13 patients with a sternal defect after cardiothoracic operations with this technique between 2010-2016. Ten patients had a deep sternal wound infection, two had an infection of the prosthesis after carotico-subclavian bypass and one had a fragmented sternum. Nine patients were treated with an internal mammary artery perforator fasciocutaneous flap with a muscle-sparing pectoralis major muscle flap and four patients with an internal mammary artery perforator fasciocutaneous flap combined with a right pectoralis major muscle flap. RESULTS: Three patients (23%) experienced major complications and four patients (31%) had conservatively treated minor complications. There were no flap losses. CONCLUSION: This combination of flaps is a suitable option for patients with large defects in whom direct skin closure is not possible. It can be utilized for defects comprising the entire vertical length of the sternum. These are local flaps with a short operation time and are therefore most suitable for patients with comorbidities in whom major surgery is not an option.

Hair cortisol concentration (HCC) as a measure for prenatal psychological distress - A systematic review.

Prenatal environment reportedly affects the programming of developmental trajectories in offspring and the modification of risks for later morbidity. Among the increasingly studied prenatal exposures are maternal psychological distress (PD) and altered maternal hypothalamus-pituitary-adrenal (HPA) axis functioning. Both prenatal PD and maternal short-term cortisol concentrations as markers for HPA axis activity have been linked to adverse child outcomes and it has been assumed that maternal PD affects the offspring partially via altered cortisol secretion patterns. Yet, the existing literature on the interrelations between these two measures is conflicting. The assessment of cortisol levels by using hair cortisol concentration (HCC) has gained interest, as it offers a way to assess long-term cortisol levels with a single non-invasive sampling. According to our review, 6 studies assessing the associations between maternal HCC during pregnancy and various types of maternal PD have been published so far. Measures of prenatal PD range from maternal symptoms of depression or anxiety to stress related to person's life situation or pregnancy. The aim of this systematic review is to critically evaluate the potential of HCC as a biomarker for maternal PD during pregnancy. We conclude that HCC appears to be inconsistently associated with self-reported symptoms of prenatal PD, especially in the range of mild to moderate symptom levels. Self-reports on PD usually cover short time periods and they seem to depict partly different phenomena than HCC. Thus, methodological aspects are in a key role in future studies evaluating the interconnections across different types of prenatal PD and maternal HPA axis functioning. Further, studies including repetitive measurements of both HCC and PD during the prenatal period are needed, as timing of the assessments is one important source of variation among current studies. The significance of prenatal HCC in the context of offspring outcomes needs to be further investigated.

Can the efficacy of reduction mammoplasty be predicted? The applicability and predictive value of breast-related symptoms questionnaire in measuring breast-related symptoms pre- and postoperatively.

To measure the impact of reduction mammoplasty, the Breast-Related Symptoms Questionnaire (BRSQ) was translated into Finnish and tested among women seeking reduction mammoplasty. This previously validated questionnaire focuses on 13 breast hypertrophy-related symptoms and their frequency. In this prospective multicentre study, the breast-related symptoms of 98 women were measured preoperatively with BRSQ and the health-related quality of life (HRQoL) with the 15 dimension (15D), a well-established generic tool. A total of 59 participants were followed up at least 6 months postoperatively. The women were middle-aged (mean age 44 years) and most of them overweight (mean Body mass index (BMI) 29). All patients had frequent physical symptoms and disability due to their breasts and reported low breast severity symptom score (BSS mean 27, range 13-38). Mean amount of resected breast tissue was 1310 g per patient. Postoperatively, the breast-related symptoms were significantly relieved, and 55 of 59 operated patients reported less frequent or non-existent symptoms (mean BSS 59, range 22-65). BSS score improved especially in obese women and those with pendulous breasts. A low preoperative BSS was related to considerable benefit from surgery. HRQoL score improved significantly from 0.889 to 0.930 (P < 0.001) and significant improvement was seen especially in dimensions, such as discomfort, usual activities and breathing. In conclusion, BRSQ is an easy tool to use to quantify breast-related symptoms. It visualised effectively the impact of the reduction mammoplasty. Surgical breast reduction significantly improves breast-related symptoms and the HRQoL among women with many breast-related symptoms. The present guidelines for patient selection in breast reduction surgery should be updated to use valid measurement and scientific evidence.

The effects of hypotension and norepinephrine on microvascular flap perfusion.

Microvascular flap surgery is a common technique in reconstructive surgery. The wide indications and variable patients provide challenge also for anesthesiologist. Both hypotension and hypoperfusion can be harmful to the flap. Hypotensive patients are treated with fluid resuscitation and vasopressors (e.g., norepinephrine), if needed. As vasoconstrictors, vasopressors might impair microvascular flap perfusion. In this experimental pig model we studied the effect of sevoflurane-induced hypotension on the perfusion of microvascular and superiorly pedicled rectus abdominis myocutaneous flaps. In addition, we evaluated the effect of norepinephrine on flap perfusion when it was used for correction of hypotension. Microdialysis (MD) was used to detect metabolic changes, as it is a sensitive method to detect early changes of tissue metabolism and ischemia in different tissue components of soft tissue flaps. The main finding of this study was that moderate degree of normovolemic hypotension or the use of norepinephrine for the correction of this hypotension did not affect flap perfusion as assessed by MD. More studies are clearly needed to confirm the safety of norepinephrine in clinical use in microsurgery.

The BH3-mimetic ABT-737 induces mast cell apoptosis in vitro and in vivo: potential for therapeutics.

Mast cells and their mediators are implicated in the pathogenesis of many different diseases. One possible therapeutic intervention in mast cell-associated diseases can be to reduce the number of tissue mast cells by inducing mast cell apoptosis. In this study, we demonstrate that mast cells exhibit a high sensitivity to ABT-737, a BH3-only mimetic molecule that induces apoptosis through high-affinity binding to the prosurvival proteins, Bcl-2, Bcl-XL, and Bcl-w. Primary mast cells as well as mast cell lines tested succumbed to apoptosis in response to the inhibitor at varying but seemingly low concentrations compared with other leukocytes investigated. I.p. injections of ABT-737 in mice resulted in a total abolishment of mast cells in the peritoneum. Confocal microscopy analysis of peritoneal cells revealed apoptotic bodies of mast cells being phagocytosed by macrophages. In addition, ex vivo treatment of human skin biopsies with ABT-737 demonstrated increased mast cell apoptosis. The data we present in this article show exceptional mast cell sensitivity to ABT-737, a selective inhibitor of antiapoptotic proteins, rendering a possible application for BH3-only mimetic compounds like ABT-737 in mast cell-associated diseases, such as mastocytosis, allergy, asthma, and other chronic inflammations.

Cost analysis of 109 microsurgical reconstructions and flap monitoring with microdialysis.

Few studies have examined the cost-effectiveness of microsurgery, and little is known about the cost-effectiveness of flap monitoring. We studied the costs related to microsurgery during 2004 to 2006 in Kuopio University Hospital. A total of 99 patients were reconstructed with 109 flaps. Primary success was achieved in 64% of cases. Reoperation for anastomosis was conducted in 25% and for other surgical complications in 27%. The intended result was achieved in 94% of cases. The mean total cost of hospital care was 20,000 euro in head and neck cancer surgery, 15,500 euro in defects of the lower extremities, and 9200 euro in breast reconstruction. The costs were greatly influenced by surgical complications (i.e., if the primary reconstruction failed, then the secondary microvascular flap almost doubled the expense involved; mean expenses per case 27,900 euro). Microdialysis was used in flap monitoring with an additional cost of 535 euro per patient. We found that microdialysis provided an early diagnosis of perfusion failure and helped to save the flap. It was estimated that if one or two flaps per year are saved due to more effective monitoring, then the extra costs of using microdialysis are covered.

[Antithrombotic medication of cardiac patient in connection with surgery and minor operations]. / Sydänpotilaan antitromboottinen lääkitys leikkausten ja pientoimenpiteiden yhteydessä.

A major proportion of cardiac patients use long-time antithromobitic medication. It is not uncommon that these patients require surgery and operations. Discontinuation of antithrombotic therapy may be used to decrease risk of hemorrhage, but on the other hand the medication break will make the patient susceptible to thrombotic and thromboembolic complications. The attending physician must decide which is safer: to break the medication or to continue it. Often the best choice is a compromise of the above, i.e. application of a somewhat reduced compensatory antithrombotic therapy.

Microdialysis detects postoperative perfusion failure in microvascular flaps.

In microvascular tissue transfers, it is essential postoperatively to follow-up on the perfusion of the transferred flap because of the risk of anastomotic failure. The diagnosis of pedicle obstruction is usually made by clinical observation, but some techniques have been reported as more reliable than clinical observation in detecting perfusion failure. The authors used microdialysis (MD), a method developed to assess in situ tissue metabolism, in the follow-up of 80 consecutive microvascular flaps from October, 2001 to October, 2003. Of the 78 flaps with postoperative data, 58 flaps were uneventful clinically and using MD, and served as the reference material for normal postoperative metabolism. Twenty flaps showed some abnormality in the clinical course or with MD. Of these, 13 flaps were reoperated for anastomosis thrombosis (9 arterial, 4 venous). All thromboses were clearly recognized by MD via a decrease in the glucose concentration in the tissue (< 2.7 mmol/l) and an increase in the lactate concentrations (> 5.7 mmol/l). In some cases, MD indicated a pathological trend in glucose and lactate concentrations hours before there were any clinical signs. A system of alarm levels was developed for the staff: when the limits were reached, a critical evaluation of the situation was undertaken, and the need for reoperation was considered. In the series, the salvage rate of all thrombosed flaps was 77 percent, with a final success rate in microvascular reconstruction of 95 percent. No flap was lost due to a delay in the diagnosis of secondary ischemia, if on-line MD monitoring was available. Microdialysis is a clinically feasible and sensitive monitoring method for all kinds of microvascular flaps, especially for those in which clinical observation is difficult or impossible. The performance of the analysis is easy and can be done by even less experienced nursing staff working in institutes with a low frequency of microsurgery.

Add-on device for stereotactic core-needle breast biopsy: how many biopsy specimens are needed for a reliable diagnosis?

PURPOSE: To prospectively determine whether there is a minimum number of cores required for histopathologic diagnosis of mammographically detected nonpalpable breast lesions with an add-on 14-gauge stereotactic core-needle biopsy device. MATERIALS AND METHODS: The study was approved by the ethics committee of the hospital; informed consent was obtained. Biopsy was performed in 197 patients with 205 lesions (97 masses, 108 microcalcifications). The first sample (from the center) was collected in container A; second and third samples (2 mm from center), in container B; and additional samples, in container C. Malignancies, atypical ductal hyperplasia (ADH), and radial scars were excised. Benign lesions were followed up mammographically (mean, 24 months). Strict sensitivity and working sensitivity were calculated separately. Stereotactic biopsy with diagnosis of a nonmalignant lesion that, after surgery, proved to be malignant was considered false-negative when strict sensitivity was calculated. Stereotactic biopsy with diagnosis of ADH or radial scar was considered true-positive if the findings at surgery corresponded to the results at biopsy or indicated malignancy and was considered false-positive if the findings at surgery were benign when working sensitivity was calculated. Sensitivity, specificity, and overall accuracy of stereotactic biopsy were determined for masses and microcalcifications in all three containers by using surgical samples and findings at mammographic follow-up as reference. At chi2 analysis, P < .05 was considered to indicate significant difference. RESULTS: Strict sensitivity of the first sample was 77% (66 of 86) (90% [35 of 39] for masses, 66% [31 of 47] for microcalcifications). Results of the first sample were false-negative significantly more often in microcalcifications (n = 16) than in masses (n = 4) (P = .010). Combined results of containers A and B (ie, three samples) yielded higher strict sensitivity than those with first sample alone (95% [37 of 39] for masses [P = .196], 91% [43 of 47] for microcalcifications [P < .001]). With multiple samples, strict and working sensitivity were both 100% (39 of 39) for masses and 91% (43 of 47) and 98% (46 of 47), respectively, for microcalcifications. Four false-negative diagnoses (ADH, three cases; lesion with discordant mammographic and stereotactic biopsy findings, one case) were microcalcifications. CONCLUSION: More than three samples are needed (a minimum number was not determined) for a histologic diagnosis of a mass lesion by using an add-on stereotactic biopsy device.

Breast lesions causing nipple discharge: preoperative galactography-aided stereotactic wire localization.

OBJECTIVE: Lesions that present with nipple discharge typically are not visible on mammography or sonography but can be detected on galactography. Therefore, the usual methods for preoperative localization (wire placement under sonography or stereotactic guidance) are not applicable. We report our preliminary experience of galactography-aided stereotactic wire (n = 8) or coil (n = 1) localization of small intraductal lesions. CONCLUSION: Galactography-aided wire or coil localization is a practical localization method for intraductal lesions not detectable on mammography or sonography.

Effects of coronary artery bypass related conduction defects: a 10-year follow-up study.

OBJECTIVES: The aim of this study is to determine the long-term prognostic significance of new permanent conduction defects (CDs) related to coronary artery bypass grafting (CABG), and to assess predisposing factors for increased mortality after CABG. DESIGN: One hundred and eighty patients who underwent an elective CABG without any evidence of preoperative CDs were followed on average for 9.6 years. Long-term outcome was observed in terms of Kaplan-Meier survival analysis, and several potential pre-, intra- and postoperative factors for increased mortality were analysed using the Cox regression model. RESULTS: Sixty-three (35.0%) of the patients developed a new CD (CD+ group) before hospital discharge. Early (<30 days) and long-term (>30 days) survival rates were 98.9 and 86.1%, respectively. The long-term survival in CD+ patients was significantly lower that in CD- patients (77.8% vs 90.4%, p = 0.02). However, cardiac survival in CD+ patients and CD- patients did not differ from each other (88.9% and 92.3%, respectively, p=NS). Five independent predictors for increased all cause mortality were identified: diabetes (relative risk ratio 5.99 [2.43-14.78]), number of distal anastomoses (3.20 [1.30-7.88]), a new intraoperative conduction defect (2.83 [95% CI 1.24-6.49]), preoperative ejection fraction <50% (2.60 [1.08-6.27]) and perfusion time (1.02 [1.01-1.03]). CONCLUSIONS: Excellent survival rates can be obtained 10 years after CABG. CDs were not related to increased cardiac mortality. The appearance of preoperative diabetes, intraoperative perfusion time, number of distal anastomoses performed, CABG derived permanent CDs and low preoperative ejection fraction are associated with higher all cause mortality during the long-term follow-up.