Signs, symptoms and biochemistry in recurrent Cushing disease: a prospective pilot study.
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ABSTRACT:
SUBMITTER: Braun LT
PROVIDER: S-EPMC8325659 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
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Signs, symptoms and biochemistry in recurrent Cushing disease: a prospective pilot study.
Braun Leah T LT Zopp Stephanie S Vogel Frederick F Honegger Jürgen J Rubinstein German G Schilbach Katharina K Künzel Heike H Beuschlein Felix F Reincke Martin M
Endocrine 20210419 3
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Project description:Postoperative testing after transsphenoidal surgery (TSS) for Cushing disease (CD) in children and its usefulness in predicting residual disease or recurrence are not well studied.The objective of the study was to identify which one of three tests that are routinely performed in our institution after TSS performs better in the identification of noncured patients or predict relapse for CD.This was a retrospective review of clinical data of 72 children who received surgery for CD (age range 5.8-18.3 yr).The study was conducted at a tertiary care center.After TSS, plasma ACTH and serum cortisol (at 0800 h), urinary free cortisol (UFC) values and an ovine CRH (oCRH) stimulation test were obtained. Patients were followed up for 24-120 months by a formal protocol.Of 72 children with CD, 66 (94%) achieved sustained remission after TSS. Two children had persistent disease after TSS, whereas four children appeared cured at first but relapsed later. All four had low or undetectable UFCs that were not different from cured patients (P > 0.0.1). Children who remained in remission had significantly lower morning ACTH and cortisol levels after TSS compared with those who relapsed (P < 0.001). During an oCRH stimulation test, ACTH and cortisol values were higher in patients who relapsed vs. those in remission (P <0.001). Lack of histological confirmation of an adenoma, normal serum cortisol or ACTH, a normal response to oCRH, and glucocorticoid replacement for less than 6 months after surgery were associated with relapse.In pediatric patients with CD, low UFCs after TSS are not good predictors of sustained remission; morning ACTH and cortisol values and/or an oCRH test after TSS predicted patients that recurred.
| S-EPMC2730862 | biostudies-other
Project description:It is currently impossible to predict the prognosis of patients with juvenile dermatomyositis (JDM). The aim of this study was to find clinical features most strongly associated with outcome variables in JDM as a first step towards tailor-made treatment.In a large, prospectively followed, multicenter cohort study of 340 patients with JDM, each contributing multiple visits, a Bayesian model of disease activity was developed, using the four continuous outcome variables creatine kinase (CK), childhood myositis assessment score (CMAS), manual muscle testing of 8 muscle groups (MMT8) and the physician's global assessment of disease activity (PGA). Covariates were clinical signs and symptoms. Correlations among visits of the same patient were resolved by introducing subject-specific random effects.Myalgia and dysphonia were associated with worse disease activity according to all outcome variables. Periorbital rash, rash on the trunk, rash over large joints, nail fold changes and facial swelling were associated with higher PGA. Notably, periorbital rash was also associated with higher CK and lower CMAS and nail fold changes with lower CMAS. Contractures were associated with lower CMAS and MMT8 and higher PGA. Patients with higher CMAS exhibited a higher MMT8 as well. PGA had the highest probability among the four outcome variables of being abnormal even if the other three outcome variables were normal.The signs and symptoms associated with disease activity could be used to stratify patients and adapt treatment plans to disease activity. The correlation between CMAS and MMT8 and the unique information captured by PGA implied that PGA should be maintained as an outcome variable, whereas CMAS and MMT8 might be simplified.
| S-EPMC6094880 | biostudies-other
Project description:BackgroundSerious infections in children (sepsis, meningitis, pneumonia, pyelonephritis, osteomyelitis, and cellulitis) are associated with considerable mortality and morbidity. In children with an acute illness, the primary care physician uses signs and symptoms to assess the probability of a serious infection and decide on further management.AimTo analyse the diagnostic accuracy of signs and symptoms, and to create a multivariable triage instrument.Design of studyA prospective diagnostic accuracy study.SettingPrimary care in Belgium.MethodChildren aged 0-16 years with an acute illness for a maximum of 5 days were included consecutively. Signs and symptoms were recorded and compared to the final outcome of these children (a serious infection for which hospitalisation was necessary). Accuracy was analysed bivariably. Multivariable triage instruments were constructed using classification and regression tree (CART) analysis.ResultsA total of 3981 children were included in the study, of which 31 were admitted to hospital with a serious infection (0.78%). Accuracy of signs and symptoms was fairly low. Classical textbook signs (meningeal irritation impaired peripheral circulation) had high specificity. The primary classification tree consisted of five knots and had sensitivity of 96.8% (95% confidence interval [CI] = 83.3 to 99.9), specificity 88.5% (95% CI = 87.5 to 89.5), positive predictive value 6.2% (95% CI = 4.2 to 8.7), and negative predictive value 100.0% (95% CI = 99.8 to 100.0), by which a serious infection can be excluded in children testing negative on the tree. The sign paramount in all trees was the physician's statement 'something is wrong'.ConclusionSome individual signs have high specificity. A serious infection can be excluded based on a limited number of signs and symptoms.
| S-EPMC2099636 | biostudies-literature
Project description:BackgroundData linking labor pain and postpartum depression are emerging. Robust, prospective evaluations of this relationship while factoring other important variables are lacking. We assessed perinatal pain and other factors predicting postpartum depression (PPD) symptoms.MethodsThird trimester women, stratified by a priori plan to receive or avoid labor epidural analgesia, were longitudinally followed from the prenatal period through labor and delivery, until 6 weeks and 3 months postpartum. Electronic pain data was collected hourly during labor in real time, capturing pain unpleasantness, intensity, pain management satisfaction, and expectations. Prenatal and postpartum data included anxiety, depression, the Brief Pain Inventory (BPI), pain catastrophizing, resiliency, and perceived social support and stress. The primary outcome was Edinburgh Postnatal Depression Score (EPDS) as a marker of PPD symptoms. The primary pain variable of interest was labor pain emotional valence (unpleasantness burden, area under the curve for entire labor duration). Single and multivariable linear regressions examined perinatal pain variables in relation to EPDS.ResultsOf 72 subjects included, 55 planned/received labor epidural analgesia and 17 planned avoidance/avoided it. In the planned epidural group, the emotional valence of labor pain independently predicted six-week EPDS (labor pain unpleasantness burden, R2?=?0.42, P?=?0.002). In addition to labor pain, prenatal and postpartum pain variables from the BPI independently predicted six-week EPDS. Three-month depression scores were linked to labor and acute pain (6 weeks postpartum), but not to chronic (3 months postpartum) pain variables. Intrapartum pain management satisfaction and expectations were largely met or exceeded and did not differ between analgesia groups.ConclusionFor susceptible women, pain at all perinatal time points-prenatal, labor, and postpartum-appear to be independently linked to depression scores at 6 weeks postpartum. The relationships are true, even though satisfaction and expectations regarding labor pain management were met or exceeded. These data support the concept that labor and acute postpartum pain influences both acute and long-term PPD symptoms, although additional data are needed to assess how analgesia preference interacts with these relationships.
| S-EPMC7178606 | biostudies-literature
Project description:Given that memantine is thought to decrease N-methyl-D-aspartic-acid-related (NMDA) glutamatergic hyperactivity and improve locomotion in rats, we sought to assess the drug's impact on axial symptoms in advanced Parkinson's disease (PD).We performed a 90-day, randomised, double-blind, study with two parallel arms: 20 mg/day memantine versus placebo (ClinicalTrials.gov:NCT01108029). The main inclusion criterion was the presence of a severe gait disorder and an abnormal, forward-leaning stance. The following parameters were analysed under standardised conditions before and after acute administration of L-dopa: gait (stride length as primary criterion), the United-Parkinson's-Disease-Rating-Scale (UPDRS) motor score and its axial subscore, the hypertonia and strength of the axial extensors and flexors (isokinetic dynamometer), the Dyskinesia Rating Scale score (DRS) and its axial subscore.Twenty-five patients were included. The memantine and placebo group did not differ significantly in terms of stride length. However, in the memantine group, we observed significantly better results (vs placebo) for the overall UPDRS score (F(1,21)=4.9; p=0.039(-1)) and its axial subscore (F(1,21)=7.2; p=0.014(-1.1)), axial hypertonia, the axial and overall DRS and axial strength.Memantine treatment was associated with lower axial motor symptom and dyskinesia scores but did not improve gait. These benefits must be confirmed in a broader population of patients.
| S-EPMC3623038 | biostudies-literature
Project description:A 50-year-old male immigrant from Ethiopia presented for consultation after 3 years of hematochezia/melena requiring > 25 units of blood transfusions. Physical examination revealed severe proximal muscle wasting and weakness, central obesity, proptosis, and abdominal striae, accompanied by eosinophilia, elevated hemoglobin A1c, elevated 24-hour urinary cortisol, lack of suppression of 8 am cortisol levels by 1 mg dexamethasone, and inappropriately elevated random adrenocorticotropic hormone (ACTH) level. Histopathological examination of gastrointestinal biopsies showed large numbers of Strongyloides stercoralis, indicating Strongyloides hyperinfection. Treatment with 2 days of ivermectin led to resolution of gastrointestinal bleeding. This syndrome was due to chronic immunosuppression from a pituitary ACTH (corticotroph) microadenoma, of which resection led to gradual normalization of urine cortisol, improved glycemic control, resolution of eosinophilia, and no recurrence of infection.
| S-EPMC4596606 | biostudies-literature
Project description:OBJECTIVE:To evaluate the association between Cushing syndrome and hypercoagulability in children. STUDY DESIGN:A prospective, observational study was performed of 54 patients with Cushing syndrome, 15.1?±?3.9 years, treated at the National Institutes of Health Clinical Center. Coagulation profiles were taken before and 6-12 months after surgery and compared with18 normocortisolemic children, 13.7?±?3.6 years. RESULTS:At baseline, patients with Cushing syndrome had greater levels of the procoagulant factor VIII (FVIII) vs controls (145?IU/dL?±?84 vs 99?±?47, P?=?.04); 6-12 months after surgery, FVIII levels decreased to 111?±?47, P?=?.05. Patients with Cushing syndrome had greater levels of the antifibrinolytic ?2-antiplasmin, 96?±?17% vs 82?±?26%, P?=?.015. After surgery, antifibrinolytic ?2-antiplasmin levels decreased to 82?±?24%, P?<?.001. Anticoagulants were greater in patients with Cushing syndrome vs controls at baseline, including protein C (138?±?41% vs 84?±?25%, P?<?.001), protein S (94?±?19% vs 74?±?19%, P?=?.001), and antithrombin III (96?±?18% vs 77?±?13%, P?<?.0001). The 24-hour urinary free cortisol levels correlated positively with FVIII levels, r?=?0.43, P?=?.004. CONCLUSION:Children with Cushing syndrome had elevated procoagulants, antifibrinolytics, and anticoagulants at baseline compared with controls; normalization of coagulation measures was seen after surgical cure. Despite the increase in anticoagulants, hypercortisolemia is associated with a hypercoagulable state in children, as is the case in adults. This finding has potential implications for prevention of venous thromboembolism in children with Cushing syndrome. TRIAL REGISTRATION:ClinicalTrials.gov:NCT00001595.
| S-EPMC5298225 | biostudies-literature
Project description:Background:To report fluorescein angiography findings in a group of albuminuric Type 1 diabetes mellitus (T1DM) patients without diabetic retinopathy. Methods:Fifteen albuminuric T1DM patients with normal/near normal estimated glomerular filtration rate without diabetic retinopathy underwent fluorescein angiography; presence of microaneurysms, vascular permeability changes and retinal malperfusion were evaluated. Results:Fluorescein angiography revealed microaneurysms, blood-retinal barrier breakdown and retinal ischemia in 10 (67%) and 11 (73%); 8 (53%) and 9 (60%); 2 (13%) and 5 (33%) of patients at baseline and follow up, respectively. Follow up time averaged 24.6 months, minimum follow up time was 20 months. Patients who presented retinal malperfusion had higher HbA1C and lower estimated glomerular filtration rate. Conclusions:Most albuminuric T1DM patients with a normal fundus exam had angiographic signs of diabetic retinopathy, some presenting retinal malperfusion. Retinal changes may be found with more sensitive testing in these patients, especially with impaired estimated glomerular filtration rate, even if the fundus exam is normal, and fluorescein angiography should be considered. These findings point to a homogenous presentation of the diabetic microangiopathies.
| S-EPMC5733928 | biostudies-literature
Project description:BackgroundParkinson's disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons.ObjectiveTo assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT).MethodsTwelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12 weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14 weeks before commencing the same treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4 weeks of treatment, after 12 weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%.ResultsMeasures of mobility, cognition, dynamic balance and fine motor skill were significantly improved (p < 0.05) with PBM treatment for 12 weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed.ConclusionsPBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted.Trial registrationAustralian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018.
| S-EPMC8249215 | biostudies-literature
Project description:OBJECTIVES:Acute mania is a serious medical condition that impacts men and women equally. Longtime presentation of manic symptoms is sex-dependent; however, little is known about acute symptoms of mania. The objective of this study is to track and compare acute manic symptoms for sex differences during inpatient hospitalization. METHODS:All patients with bipolar mania admitted to a large university hospital between January and October 2017 were invited to participate in this longitudinal naturalistic follow-up study. Manic (YMRS), depressive (MADRS), and psychotic (PAS) symptoms were tracked daily from admission to discharge. RESULTS:The total YMRS scores decreased significantly overtime (p < .0001) in both male (n = 34) and female (n = 23) patients (p = .7). However, male patients scored significantly higher in sexual interest (p = .01), disruptive and aggressive behavior (p = .01), and appearance (p < .001) while females had better insight into their illness (p = .01). Males and females received similar doses of lithium (p = .1), but males received significantly higher doses of valproic acid (VPA) in comparison with females (p = .003). However, plasma lithium and VPA concentrations at discharge were not significantly different between sexes. CONCLUSION:Our results show sex differences in the progression of certain domains of manic symptoms in a cohort of 23 female and 34 male patients admitted to a large academic center in Turkey. Males, in this sample, exhibited more sexual interest, disruptive and aggressive behaviors, better grooming, and less insight compared to females. While these results are concordant with our preclinical findings and with anecdotal clinical observations, replication in larger samples is needed.
| S-EPMC7066352 | biostudies-literature