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Aims: To compare the effects of Ayurvedic and conventional nutritional therapy in patients with irritable bowel syndrome (IBS). Methods: Sixty-nine patients with IBS were randomized to Ayurvedic (n = 35) or conventional nutritional therapy according to the recommendations of the German Nutrition Society including the low-FODMAP diet (n = 34). Study visits took place at baseline and after 1, 3, and 6 months. The primary outcome was IBS symptom severity (IBS-SSS) after 3 months; secondary outcomes included stress (CPSS), anxiety and depression (HADS), well-being (WHO-5) and IBS-specific quality of life (IBS-QOL). A repeated measures general linear model (GLM) for intent-to-treat-analyses was applied in this explorative study. Results: After 3 months, estimated marginal means for IBS-SSS reductions were 123.8 [95% confidence interval (95% CI) = 92.8–154.9; p < 0.001] in the Ayurvedic and 72.7 (95% CI = 38.8–106.7; p < 0.001) in the conventional group. The IBS-SSS reduction was significantly higher in the Ayurveda group compared to the conventional therapy group (estimated marginal mean = 51.1; 95% CI = 3.8–98.5; p = 0.035) and clinically meaningful. Sixty-eight percentage of the variance in IBS-SSS reduction after 3 months can be explained by treatment, 6.5% by patients' expectations for their therapies and 23.4% by IBS-SSS at pre-intervention. Both therapies are equivalent in their contribution to the outcome variance. The higher the IBS-SSS score at pre-intervention and the larger the patients' expectations, the greater the IBS-SSS reduction. There were no significant group differences in any secondary outcome measures. No serious adverse events occurred in either group. Conclusion: Patients with IBS seem to benefit significantly from Ayurvedic or conventional nutritional therapy. The results warrant further studies with longer-term follow-ups and larger sample sizes. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03019861, identifier: NCT03019861.
Der Morbus Basedow zählt zu den häufigsten Ursachen einer Hyperthyreose. Zur Behandlung stehen neben der medikamentösen thyreostatischen Therapie auch ein operatives sowie ein nuklearmedizinisches Verfahren zur Verfügung.
Die beiden zuletzt genannten Behandlungsmöglichkeiten stellen aufgrund ihrer Wirkungsweise ein definitives Verfahren dar, bei dem Schilddrüsengewebe entfernt bzw. zerstört wird. Dadurch ist in der Regel eine dauerhafte Substitution der lebensnotwendigen Schilddrüsenhormone erforderlich. Im Gegensatz dazu bleibt bei der medikamentösen Therapie mit Thyreostatika die gesamte Schilddrüse erhalten und funktionsfähig. Der Nachteil besteht in der hohen Rezidivrate von über 50 % im Vergleich zur definitiven Therapie. Damit mehr Patienten von den Vorteilen der thyreostatischen Therapie profitieren, ist eine Optimierung dieser zur Reduktion der Rezidivrate notwendig.
Ziel dieser Arbeit war es, mittels einer retrospektiven Analyse zu ermitteln, welche anamnestischen, klinischen, sonographischen und laborchemischen Parameter mit einem Rezidiv des Morbus Basedow bei Patienten mit thyreostatischer Therapie in Zusammenhang stehen. Weiterhin erfolgte eine Analyse von sonographischen und laborchemischen Werten im Krankheitsverlauf, um daraus Indikatoren für eine optimale Dauer der thyreostatischen Therapie abzuleiten. Hierzu wurden die Daten von 260 Patienten bezüglich der folgenden Faktoren zwischen Remissions- und Rezidivgruppe verglichen: Erkrankungsalter, Geschlecht, Dauer der Thyreostatikagabe, Vitamin D-Spiegel, Nikotinkonsum, endokrine Orbitopathie, fam. Autoimmunerkrankung, fam. Schilddrüsenerkrankung und Veränderungen im Hormonhaushalt anderer Hormonachsen. Zudem erfolgte eine Zeitreihenanalyse Schilddrüsen-spezifischer Laborwerte (fT3, fT4, TSH, TRAK, anti-TPO-Ak, TgAk) und des sonographisch bestimmten Schilddrüsenvolumens jeweils zu den Zeitpunkten Diagnosestellung sowie sechs und zwölf Monate darauf. Die Rezidivrate im untersuchten Patientenkollektiv betrug 68,8 %.
Für das Erkrankungsalter, die Therapiedauer, das Schilddrüsenvolumen, die Schilddrüsenfunktionsparameter und die TSH-Rezeptor-Antikörper ließen sich signifikante Unterschiede zwischen Remissions- und Rezidivkohorte nachweisen. Patienten, die bei Diagnose das 35. Lebensjahr noch nicht vollendet hatten, erlitten signifikant häufiger ein Rezidiv als ältere Patienten. In der Remissionsgruppe war die Therapiedauer mit zwölf Monaten zudem signifikant länger als in der Rezidivgruppe. Patienten, deren Schilddrüse zum Zeitpunkt der Diagnose oder zwölf Monate darauf in der sonographischen Messung über die Norm vergrößert war, erlitten signifikant häufiger ein Rezidiv des Morbus Basedow, ebenso wie Patienten mit anhaltend pathologischen Schilddrüsenfunktionsparametern sechs und zwölf Monate nach Diagnose. Die Werte der TSH-Rezeptor-Antikörper fielen in der Rezidivgruppe zu allen Erhebungszeitpunkten signifikant höher aus als in der Remissionsgruppe. Diese Ergebnisse lassen für die medikamentöse Behandlung des Morbus Basedow den Schluss zu, dass die Dauer der thyreostatischen Therapie dem Krankheitsverlauf, der sich in den Schilddrüsenfunktionswerten und den Leveln der TSH-Rezeptor-Antikörper widerspiegelt, angepasst werden sollte, um deren Erfolgsrate zu steigern. Weiterhin lässt sich folgern, dass bei jüngeren Patienten und Patienten mit vergrößerter Schilddrüse ein erhöhtes Rezidivrisiko besteht und diese Patienten möglicherweise von einem verlängerten Therapieintervall profitieren.
Während in der aktuellen europäischen Leitlinie zur Behandlung der Immunhyperthyreose eine feste Spanne von zwölf bis achtzehn Monaten für die Gabe der Thyreostatika empfohlen wird, lautet die Empfehlung der amerikanischen Hyperthyreose-Leitlinie die thyreostatische Therapie bis zur Normalisierung der TSH-Rezeptor-Antikörper fortzuführen. Die Ergebnisse der vorliegenden Arbeit sprechen dafür, die europäische Leitlinie dahingehend der amerikanischen Leitlinie anzupassen.
In psychiatry, there has been a growing focus on identifying at-risk populations. For schizophrenia, these efforts have led to the development of early recognition and intervention measures. Despite a similar disease burden, the populations at risk of bipolar disorder have not been sufficiently characterized. Within the BipoLife consortium, we used magnetic resonance imaging (MRI) data from a multicenter study to assess structural gray matter alterations in N = 263 help-seeking individuals from seven study sites. We defined the risk using the EPIbipolar assessment tool as no-risk, low-risk, and high-risk and used a region-of-interest approach (ROI) based on the results of two large-scale multicenter studies of bipolar disorder by the ENIGMA working group. We detected significant differences in the thickness of the left pars opercularis (Cohen’s d = 0.47, p = 0.024) between groups. The cortex was significantly thinner in high-risk individuals compared to those in the no-risk group (p = 0.011). We detected no differences in the hippocampal volume. Exploratory analyses revealed no significant differences in other cortical or subcortical regions. The thinner cortex in help-seeking individuals at risk of bipolar disorder is in line with previous findings in patients with the established disorder and corresponds to the region of the highest effect size in the ENIGMA study of cortical alterations. Structural alterations in prefrontal cortex might be a trait marker of bipolar risk. This is the largest structural MRI study of help-seeking individuals at increased risk of bipolar disorder.
Periodontal furcation lesions: a survey of diagnosis and management by general dental practitioners
(2021)
Aim: The aim of this study was to explore general dental practitioners' (GDPs) attitude to periodontal furcation involvement (FI). Materials and methods: An online survey focused on diagnosis and management of periodontal FI was circulated to GDPs in seven different countries. Results: A total of 400 responses were collected. Nearly a fifth of participants reported rarely or never taking 6-point pocket charts; 65.8% of participants had access to a Nabers probe in their practice. When shown clinical pictures and radiographs of FI-involved molars, the majority of participants correctly diagnosed it. Although 47.1% of participants were very/extremely confident in detecting FI, only 8.9% felt very/extremely confident at treating it. Differences in responses were detected according to country and year of qualification, with a trend towards less interest in periodontal diagnosis and treatment in younger generations. Lack of knowledge of management/referral pathways (reported by 22.8%) and lack of correct equipment were considered the biggest barriers to FI management. Most participants (80.9%) were interested in learning more about FI, ideally face to face followed by online tutorials. Conclusions: Plans should be put in place to improve general dentists' knowledge and ability to manage FI, as this can have a significant impact on public health.
Cytochrome P450 (CYP) signalling pathway has been shown to play a vital role in the vasoreactivity of wild type mouse ophthalmic artery. In this study, we determined the expression, vascular responses and potential mechanisms of the CYP-derived arachidonic acid metabolites. The expression of murine CYP (Cyp2c44) and soluble epoxide hydrolase (sEH) in the wild type ophthalmic artery was determined with immunofluorescence, which showed predominant expression of Cyp2c44 in the vascular smooth muscle cells (VSMC), while sEH was found mainly in the endothelium of the wild type ophthalmic artery. Artery of Cyp2c44−/− and sEH−/− mice were used as negative controls. Targeted mass spectrometry-based lipidomics analysis of endogenous epoxide and diols of the wild type artery detected only 14, 15-EET. Vasorelaxant responses of isolated vessels in response to selective pharmacological blockers and agonist were analysed ex vivo. Direct antagonism of epoxyeicosatrienoic acids (EETs) with a selective inhibitor caused partial vasodilation, suggesting that EETs may behave as vasoconstrictors. Exogenous administration of synthetic EET regioisomers significantly constricted the vessels in a concentration-dependent manner, with the strongest responses elicited by 11, 12- and 14, 15-EETs. Our results provide the first experimental evidence that Cyp2c44-derived EETs in the VSMC mediate vasoconstriction of the ophthalmic artery.
Objectives: To test the effect of race/ethnicity on cancer-specific mortality after radical prostatectomy or external beam radiotherapy in localized prostate cancer patients. Methods: In the Surveillance, Epidemiology and End Results database 2004–2016, we identified intermediate-risk and high-risk white (n = 151 632), Asian (n = 11 189), Hispanic/Latino (n = 20 077) and African American (n = 32 550) localized prostate cancer patients, treated with external beam radiotherapy or radical prostatectomy. Race/ethnicity-stratified cancer-specific mortality analyses relied on competing risks regression, after propensity score matching for patient and cancer characteristics. Results: Compared with white patients, Asian intermediate- and high-risk external beam radiotherapy patients showed lower cancer-specific mortality (hazard ratio 0.58 and 0.70, respectively, both P ≤ 0.02). Additionally, Asian high-risk radical prostatectomy patients also showed lower cancer-specific mortality than white patients (hazard ratio 0.72, P = 0.04), but not Asian intermediate-risk radical prostatectomy patients (P = 0.08). Conversely, compared with white patients, African American intermediate-risk radical prostatectomy patients showed higher cancer-specific mortality (hazard ratio 1.36, P = 0.01), but not African American high-risk radical prostatectomy or intermediate- and high-risk external beam radiotherapy patients (all P ≥ 0.2). Finally, compared with white people, no cancer-specific mortality differences were recorded for Hispanic/Latino patients after external beam radiotherapy or radical prostatectomy, in both risk levels (P ≥ 0.2). Conclusions: Relative to white patients, an important cancer-specific mortality advantage applies to intermediate-risk and high-risk Asian prostate cancer patients treated with external beam radiotherapy, and to high-risk Asian patients treated with radical prostatectomy. These observations should be considered in pretreatment risk stratification and decision-making.
Inflammatory diseases including psoriasis are associated with metabolic and cardiovascular comorbidities, including obesity and metabolic syndrome. Obesity is associated with greater psoriasis disease severity and reduced response to treatment. Therefore, targeting metabolic comorbidities could improve patients’ health status and psoriasis-specific outcomes. METABOLyx is a randomized controlled trial evaluating the combination of a lifestyle intervention program with secukinumab treatment in psoriasis. Here, the rationale, methodology and baseline patient characteristics of METABOLyx are presented. A total of 768 patients with concomitant moderate to severe plaque psoriasis and metabolic syndrome were randomized to secukinumab 300 mg, or secukinumab 300 mg plus a tailored lifestyle intervention program, over 24 weeks. A substudy of immunologic and metabolic biomarkers is ongoing. The primary endpoint of METABOLyx is PASI90 response at week 24. Other endpoints include patient-reported outcomes and safety. METABOLyx represents the first large scale clinical trial of an immunomodulatory biologic in combination with a standardized lifestyle intervention.
Cardiac rehabilitation (CR) is a multidisciplinary intervention including patient assessment and medical actions to promote stabilization, management of cardiovascular risk factors, vocational support, psychosocial management, physical activity counselling, and prescription of exercise training. Millions of people with cardiac implantable electronic devices live in Europe and their numbers are progressively increasing, therefore, large subsets of patients admitted in CR facilities have a cardiac implantable electronic device. Patients who are cardiac implantable electronic devices recipients are considered eligible for a CR programme. This is not only related to the underlying heart disease but also to specific issues, such as psychological adaptation to living with an implanted device and, in implantable cardioverter-defibrillator patients, the risk of arrhythmia, syncope, and sudden cardiac death. Therefore, these patients should receive special attention, as their needs may differ from other patients participating in CR. As evidence from studies of CR in patients with cardiac implantable electronic devices is sparse, detailed clinical practice guidelines are lacking. Here, we aim to provide practical recommendations for CR in cardiac implantable electronic devices recipients in order to increase CR implementation, efficacy, and safety in this subset of patients.
(1) Background: The aim of our study was to identify specific risk factors for fatal outcome in critically ill COVID-19 patients. (2) Methods: Our data set consisted of 840 patients enclosed in the LEOSS registry. Using lasso regression for variable selection, a multifactorial logistic regression model was fitted to the response variable survival. Specific risk factors and their odds ratios were derived. A nomogram was developed as a graphical representation of the model. (3) Results: 14 variables were identified as independent factors contributing to the risk of death for critically ill COVID-19 patients: age (OR 1.08, CI 1.06–1.10), cardiovascular disease (OR 1.64, CI 1.06–2.55), pulmonary disease (OR 1.87, CI 1.16–3.03), baseline Statin treatment (0.54, CI 0.33–0.87), oxygen saturation (unit = 1%, OR 0.94, CI 0.92–0.96), leukocytes (unit 1000/μL, OR 1.04, CI 1.01–1.07), lymphocytes (unit 100/μL, OR 0.96, CI 0.94–0.99), platelets (unit 100,000/μL, OR 0.70, CI 0.62–0.80), procalcitonin (unit ng/mL, OR 1.11, CI 1.05–1.18), kidney failure (OR 1.68, CI 1.05–2.70), congestive heart failure (OR 2.62, CI 1.11–6.21), severe liver failure (OR 4.93, CI 1.94–12.52), and a quick SOFA score of 3 (OR 1.78, CI 1.14–2.78). The nomogram graphically displays the importance of these 14 factors for mortality. (4) Conclusions: There are risk factors that are specific to the subpopulation of critically ill COVID-19 patients.
Severe traumatic injury induces phenotypic and functional changes of neutrophils and monocytes
(2021)
Background: Severe traumatic injury has been associated with high susceptibility for the development of secondary complications caused by dysbalanced immune response. As the first line of the cellular immune response, neutrophils and monocytes recruited to the site of tissue damage and/or infection, are divided into three different subsets according to their CD16/CD62L and CD16/CD14 expression, respectively. Their differential functions have not yet been clearly understood. Thus, we evaluated the phenotypic changes of neutrophil and monocyte subsets among their functionality regarding oxidative burst and the phagocytic capacity in severely traumatized patients. Methods: Peripheral blood was withdrawn from severely injured trauma patients (TP; n = 15, ISS ≥ 16) within the first 12 h post-trauma and from healthy volunteers (HV; n = 15) and stimulated with fMLP and PMA. CD16dimCD62Lbright (immature), CD16brightCD62Lbright (mature) and CD16brightCD62Ldim (CD62Llow) neutrophil subsets and CD14brightCD16− (classical), CD14brightCD16+ (intermediate) and CD14dimCD16+ (non-classical) monocyte subsets of HV and TP were either directly analyzed by flow cytometry or the examined subsets of HV were sorted first by fluorescence-activated cell sorting and subsequently analyzed. Subset-specific generation of reactive oxygen species (ROS) and of E. coli bioparticle phagocytosis were evaluated. Results: In TP, the counts of immature neutrophils were significantly increased vs. HV. The numbers of mature and CD62Ldim neutrophils remained unchanged but the production of ROS was significantly enhanced in TP vs. HV and the stimulation with fMLP significantly increased the generation of ROS in the mature and CD62Ldim neutrophils of HV. The counts of phagocyting neutrophils did not change but the mean phagocytic capacity showed an increasing trend in TP. In TP, the monocytes shifted toward the intermediate phenotype, whereas the classical and non-classical monocytes became less abundant. ROS generation was significantly increased in all monocyte subsets in TP vs. HV and PMA stimulation significantly increased those level in both, HV and TP. However, the PMA-induced mean ROS generation was significantly lower in intermediate monocytes of TP vs. HV. Sorting of monocyte and neutrophil subsets revealed a significant increase of ROS and decrease of phagocytic capacity vs. whole blood analysis. Conclusions: Neutrophils and monocytes display a phenotypic shift following severe injury. The increased functional abnormalities of certain subsets may contribute to the dysbalanced immune response and attenuate the antimicrobial function and thus, may represent a potential therapeutic target. Further studies on isolated subsets are necessary for evaluation of their physiological role after severe traumatic injury.