The Role of Endocrine and Metabolic System in COVID-19 Disease - The Transcampus Experience and Review of Evidence From International Collaborating Groups.

The COVID-19 Pandemic has led to a world health crisis with major socioeconomic consequences that have deeply affected our daily lives. Until the end of May 2022, more than 500 million people have been infected by COVID-19 and more than 6 million have died from the disease. Unprecedented efforts in research, illustrated by the more than 250 000 publications in PubMed, have led to the identification of important pathophysiological mechanisms affected by SARS-CoV-2 and have resulted in the development of effective vaccines and treatment protocols for patients with COVID-19.

The Potential of Electrical Stimulation and Smart Textiles for Patients with Diabetes Mellitus.

Diabetes mellitus is one of the most frequent diseases in the general population. Electrical stimulation is a treatment modality based on the transmission of electrical pulses into the body that has been widely used for improving wound healing and for managing acute and chronic pain. Here, we discuss recent advancements in electroceuticals and haptic/smart devices for quality of life and present in which patients and how electrical stimulation may prove to be useful for the treatment of diabetes-related complications.

Sexual dimorphism in COVID-19: potential clinical and public health implications.

Current evidence suggests that severity and mortality of COVID-19 is higher in men than in women, whereas women might be at increased risk of COVID-19 reinfection and development of long COVID. Differences between sexes have been observed in other infectious diseases and in the response to vaccines. Sex-specific expression patterns of proteins mediating virus binding and entry, and divergent reactions of the immune and endocrine system, in particular the hypothalamic-pituitary-adrenal axis, in response to acute stress might explain the higher severity of COVID-19 in men. In this Personal View, we discuss how sex hormones, comorbidities, and the sex chromosome complement influence these mechanisms in the context of COVID-19. Due to its role in the severity and progression of SARS-CoV-2 infections, we argue that sexual dimorphism has potential implications for disease treatment, public health measures, and follow-up of patients predisposed to the development of long COVID. We suggest that sex differences could be considered in future pandemic surveillance and treatment of patients with COVID-19 to help to achieve better disease stratification and improved outcomes.

[Practical recommendations for screening and management of functional disorders of the adrenal cortex in cases of SARS-CoV-2 infections]. / Praktische Empfehlungen zum Screening und Management von Funktionsstörungen der Nebennierenrinde bei einer akuten SARS-CoV-2-Infektion.

Diseases of the adrenal cortex require particular attention during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Firstly, SARS-CoV­2 infections can give rise to extrapulmonary manifestations and cause endocrine disorders, particularly in the adrenal cortex. Furthermore, patients with pre-existing insufficiency of the adrenal cortex or hypercortisonism are particularly at risk from a severe infection such as SARS-CoV­2, to suffer from additional complications or a more severe course of a SARS-CoV­2 infection with a higher mortality. Especially in hemodynamically unstable patients with a SARS-CoV­2 infection, diseases of the adrenal glands should also be considered in the differential diagnostics and if necessary clarified, if this is not already known. Prolonged treatment of patients with a SARS-CoV­2 infection with regimens containing high doses of glucocorticoids can also result in a secondary adrenal insufficiency. In order to address these special aspects, some practical recommendations for the diagnostic and therapeutic management of functional disorders of the adrenal glands in patients with a SARS-CoV­2 infection are therefore presented.

An Update on Addison's Disease.

Addison's disease - the traditional term for primary adrenal insufficiency (PAI) - is defined as the clinical manifestation of chronic glucocorticoid- and/or mineralocorticoid deficiency due to failure of the adrenal cortex which may result in an adrenal crisis with potentially life-threatening consequences. Even though efficient and safe pharmaceutical preparations for the substitution of endogenous gluco- and mineralocorticoids are established in therapy, the mortality in patients with PAI is still increased and the health-related quality of life (HRQoL) is often reduced.PAI is a rare disease but recent data report an increasing prevalence. In addition to the common "classical" causes of PAI like autoimmune, infectious, neoplastic and genetic disorders, other iatrogenic conditions - mostly pharmacological side effects (e. g., adrenal haemorrhage associated with anticoagulants, drugs affecting glucocorticoid synthesis, action or metabolism and some of the novel anti-cancer checkpoint inhibitors) are contributing factors to this phenomenon.Due to the rarity of the disease and often non-specific symptoms at least in the early stages, PAI is frequently not considered resulting in a delayed diagnosis. Successful therapy is mainly based on adequate patient education as a cornerstone in the prevention and management of adrenal crisis. A focus of current research is in the development of pharmacokinetically optimized glucocorticoid preparations as well as regenerative therapies.

[PCSK9 Inhibitors - the magic bullet for LDL cholesterol reduction?]. / PCSK9-Inhibitoren - Durchbruch bei der LDL-Cholesterin-Senkung?

The proprotein convertase subtilisin / kexin type 9 (PCSK9) plays an important role in LDL cholesterol (LDL-C) metabolism. Subjects harboring loss-of-function mutations in the gene encoding for PCSK9 display markedly reduced LDL-C plasma levels. PCSK9 is secreted by the liver, binds to the LDL receptor and, following endocytosis, induces lysosomal degradation of the receptor together with the bound LDL-C. Current PCSK9 inhibitors are monoclonal antibodies that specifically absorb PCSK9. Subsequently, instead of being degraded the receptor can dissociate from LDL-C and recycle, consecutively resulting in an increased hepatocyte LDL receptor density and higher LDL-C clearance. In clinical trials, the PCSK9 inhibitors alirocumab and evolocumab induced reductions in LDL-C of up to 70 % in statin-treated as well as statin-naïve patients. So far, serious side effects (requiring cessation of drug treatment) occurred only in rare cases. Since this new class of lipid lowering drugs promises a high potential benefit, they have been approved by the EMA even before completion of the studies addressing clinically relevant endpoints like cardiovascular events and mortality. Therefore, the expected publication of these study results in 2017 may allow a better assessment of the efficacy and safety of PCSK9 inhibitors.

Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline.

OBJECTIVE: This clinical practice guideline addresses the diagnosis and treatment of primary adrenal insufficiency. PARTICIPANTS: The Task Force included a chair, selected by The Clinical Guidelines Subcommittee of the Endocrine Society, eight additional clinicians experienced with the disease, a methodologist, and a medical writer. The co-sponsoring associations (European Society of Endocrinology and the American Association for Clinical Chemistry) had participating members. The Task Force received no corporate funding or remuneration in connection with this review. EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to determine the strength of recommendations and the quality of evidence. CONSENSUS PROCESS: The evidence used to formulate recommendations was derived from two commissioned systematic reviews as well as other published systematic reviews and studies identified by the Task Force. The guideline was reviewed and approved sequentially by the Endocrine Society's Clinical Guidelines Subcommittee and Clinical Affairs Core Committee, members responding to a web posting, and the Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. CONCLUSIONS: We recommend diagnostic tests for the exclusion of primary adrenal insufficiency in all patients with indicative clinical symptoms or signs. In particular, we suggest a low diagnostic (and therapeutic) threshold in acutely ill patients, as well as in patients with predisposing factors. This is also recommended for pregnant women with unexplained persistent nausea, fatigue, and hypotension. We recommend a short corticotropin test (250 µg) as the "gold standard" diagnostic tool to establish the diagnosis. If a short corticotropin test is not possible in the first instance, we recommend an initial screening procedure comprising the measurement of morning plasma ACTH and cortisol levels. Diagnosis of the underlying cause should include a validated assay of autoantibodies against 21-hydroxylase. In autoantibody-negative individuals, other causes should be sought. We recommend once-daily fludrocortisone (median, 0.1 mg) and hydrocortisone (15-25 mg/d) or cortisone acetate replacement (20-35 mg/d) applied in two to three daily doses in adults. In children, hydrocortisone (∼8 mg/m(2)/d) is recommended. Patients should be educated about stress dosing and equipped with a steroid card and glucocorticoid preparation for parenteral emergency administration. Follow-up should aim at monitoring appropriate dosing of corticosteroids and associated autoimmune diseases, particularly autoimmune thyroid disease.

Coping with delusions in schizophrenia and affective disorder with psychotic symptoms: the relationship between coping strategies and dimensions of delusion.

BACKGROUND: Self-generated coping strategies and the enhancement of coping strategies are effective in the treatment of psychotic symptoms. Evaluating these strategies can be of clinical interest to develop better coping enhancement therapies. Cognitive models consider delusions as multidimensional phenomena. Using a psychometric approach, the relationship between coping and the dimensions of delusion were examined. METHODS: Thirty schizophrenia spectrum patients with delusions and 29 patients with affective disorder with psychotic symptoms were interviewed using the Heidelberg Coping Scales for Delusions and the Heidelberg Profile of Delusional Experience. Analyses of variance were conducted to investigate differences between the groups, and Spearman's rank-based correlations were used to examine the correlations between coping factors and the dimensions of delusion. RESULTS: Schizophrenia spectrum patients used more medical care and symptomatic coping, whereas patients with affective disorder engaged in more depressive coping. In the schizophrenia spectrum sample, the action-oriented, the cognitive, and the emotional dimensions of delusion were related to coping factors. In patients with affective disorder, only the action-oriented dimension was related to coping factors. CONCLUSION: Patients with schizophrenia and affective disorder cope differently with delusions. The dimensions of delusion are related to coping and should be regarded when using cognitive therapy approaches to enhance coping strategies.

Modulation of the pancreatic islet-stress axis as a novel potential therapeutic target in diabetes mellitus.

Loss of pancreatic islet function and insulin-producing beta cell mass is a central hallmark in the pathogenesis of both type 1 and type 2 diabetes. While in type 1 diabetes this phenomenon is due to an extensive destruction of beta cells caused by an autoimmune process, the mechanisms resulting in beta cell failure in type 2 diabetes are different and less clear. Also, beta cell destruction in type 1 diabetes occurs early and is the initial step in the pathogenetic process, while beta cell loss in type 2 diabetes after an initial phase of hyperinsulinemia due to the underlying insulin resistance occurs relatively late and it is less pronounced. Since diabetes mellitus is the most frequent endocrine disease, with an increasing high prevalence worldwide, huge efforts have been made over the past many decades to identify predisposing genetic, environmental, and nutritional factors in order to develop effective strategies to prevent the disease. In parallel, extensive studies in different cell systems and animal models have helped to elucidate our understanding of the physiologic function of islets and to gain insight into the immunological and non-immunological mechanisms of beta cell destruction and failure. Furthermore, currently emerging concepts of beta cell regeneration (e.g., the restoration of the beta cell pool by regenerative, proliferative and antiapoptotic processes, and recovery of physiologic islet function) apparently is yielding the first promising results. Recent insights into the complex endocrine and paracrine mechanisms regulating the physiologic function of pancreatic islets, as well as beta cell life and death, constitute an essential part of this new and exciting area of diabetology. For example, understanding of the physiological role of glucagon-like peptide 1 has resulted in the successful clinical implementation of incretin-based therapies over the last years. Further, recent data suggesting paracrine effects of growth hormone-releasing hormone and corticotropin-releasing hormone on the regulation of pancreatic islet function, survival, and proliferation as well as on local glucocorticoid metabolism provide evidence for a potential role of the pancreatic islet-stress axis in the pathophysiology of diabetes mellitus. In this chapter, we provide a comprehensive overview of current preventive and regenerative concepts as a basis for the development of novel therapeutic approaches to the treatment of diabetes mellitus. A particular focus is given on the potential of the pancreatic islet-stress axis in the development of novel regenerative strategies.

Current aspects in the pathophysiology and treatment of chronic wounds in diabetes mellitus.

Impaired wound healing is a frequent and very severe problem in patients with diabetes mellitus, yet little is known about the underlying pathomechanisms. In this paper we review the biology of wound healing with particular attention to the pathophysiology of chronic wounds in diabetic patients. The standard treatment of diabetic ulcers includes measures to optimize glycemic control as well as extensive debridement, infection elimination by antibiotic therapy based on wound pathogen cultures, the use of moisture dressings, and offloading high pressure from the wound bed. In this paper we discuss novel adjuvant therapies with particular reference to the use of autologous skin transplants for the treatment of diabetic foot ulcers which do not respond to standard care.

Structured health care for subjects with diabetic foot ulcers results in a reduction of major amputation rates.

OBJECTIVE: We tested the effects of structured health care for the diabetic foot in one region in Germany aiming to reduce the number of major amputations. RESEARCH DESIGN AND METHODS: In a prospective study we investigated patients with diabetic foot in a structured system of outpatient, in-patient and rehabilitative treatment. Subjects were recruited between January 1st, 2000 and December 31, 2007. All participants underwent a two-year follow-up. The modified University of Texas Wound Classification System (UT) was the basis for documentation and data analysis. We evaluated numbers of major amputations, rates of ulcer healing and mortality. In order to compare the effect of the structured health care program with usual care in patients with diabetic foot we evaluated the same parameters at another regional hospital without interdisciplinary care of diabetic foot (controls). RESULTS: 684 patients with diabetic foot and 508 controls were investigated. At discharge from hospital 28.3% (structured health care program, SHC) vs. 23.0% (controls) of all ulcers had healed completely. 51.5% (SHC) vs. 49.8% (controls) were in UT grade 1.Major amputations were performed in 32 subjects of the structured health care program group (4.7%) vs. 110 (21.7%) in controls (p<0.0001). Mortality during hospitalization was 2.5% (SHC) vs. 9.4% in controls (p<0.001). CONCLUSIONS: With the structured health care program we achieved a significant reduction of major amputation rates by more than 75% as compared to standard care.

Heidelberg Coping Scales for Delusions: psychometric evaluation of an expert rating instrument.

BACKGROUND: Coping is of substantial relevance in the treatment and course of psychiatric disorders. Standardized instruments to assess coping with psychotic symptoms, particularly delusions, are rare. The aim of this study was to develop and evaluate the psychometric properties of a new instrument to assess coping strategies in the context of delusional experiences: the Heidelberg Coping Scales for Delusions (HCSD). METHODS: Two hundred and twelve inpatients with schizophrenia spectrum disorders and affective disorders currently experiencing delusions were interviewed with the HCSD and other coping assessment instruments. Psychometric properties and factor structure were analyzed. RESULTS: The HCSD showed good inter-rater reliability and convergent validity. Factor analysis yielded an interpretable structure with five factors: resource-oriented coping, medical care, distraction, cognitive coping, and depressive coping. Symptomatic behavior, due to its particular characteristics, was considered apart. CONCLUSION: The HCSD is a reliable and valid instrument for the assessment of coping strategies in patients with delusions. Further research is needed to evaluate coping changes over time and their influence on treatment and clinical outcomes.

Front end with offset-free symmetrical current source optimized for time domain impedance spectroscopy.

Fast impedance measurements are often performed in time domain utilizing broad bandwidth excitation signals. Other than in frequency domain measurements harmonic distortion cannot be compensated which requires careful design of the analog front end. In order to minimize the influence of electrode polarization and noise, especially in low-frequency measurements, current injection shows several advantages compared to voltage application. Here, we show an active front end based on a voltage-controlled current source for a wide range of impedances. Using proper feedback, the majority of the parasitic capacitances are compensated. The bandwidth ranges from dc to 20 MHz for impedance magnitude below 5 kΩ. The output is a symmetric signal without dc-offset which is accomplished by combination of a current conveyor and a voltage inverter. An independent feedback loop compensates the offset arising from asymmetries within the circuitry. We focused especially on the stability of the current source for usage with small metal electrodes in aqueous solutions. At the monitor side two identical, high input impedance difference amplifiers convert the net current through the object and the voltage dropping across into a 50 Ω symmetric output. The entire circuitry is optimized for step response making it suitable for fast time domain measurements.

Noninvasive management of the diabetic foot with critical limb ischemia: current options and future perspectives.

Foot ulcers are a major complication in patients with diabetes mellitus and involve dramatic restrictions to quality of life and also lead to enormous socio-economical loss due to the high amputation rate. The poor and slow wound healing is often aggravated by the frequent comorbidity of foot ulcers with peripheral arterial disease, making the treatment of this condition even more complicated. While the local treatment of foot ulcers is mainly based on mechanical relief and prevention or treatment of infection, improving perfusion of the impaired tissue remains the major challenge in peripheral arterial disease. While focal arterial stenosis is the domain of interventional angioplasty or vascular surgery, patients with critical limb ischemia and lacking options for revascularization have a much worse prognosis, because current treatment options avoiding amputation are scarce. However, based on recent research efforts, there is rising hope for promising and more-effective therapeutic approaches for these patients. Here, we discuss the current improvements of established therapies aimed at an improvement of limb perfusion, as well as the development of novel cutting-edge therapies based on stem-cell technology. The experiences of a 'high-volume center' for treatment of diabetic foot syndrome with a current major amputation rate of 4% are discussed.