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Veterinary Journal (London, England :... 2023Steroid-responsive meningitis-arteritis (SRMA) occurs as an immune-mediated, inflammatory, and non-infectious disorder of juvenile and young-adult dogs. In principle,... (Review)
Review
Steroid-responsive meningitis-arteritis (SRMA) occurs as an immune-mediated, inflammatory, and non-infectious disorder of juvenile and young-adult dogs. In principle, SRMA is divided into two clinical courses: during the typical acute form, dogs are presented with fever, cervical hyperaesthesia, and reluctance to move. The more protracted form most probably emerges after insufficient immunosuppressive treatment or relapses, with additional neurologic deficits localized in the cervical and thoracolumbar spinal cord or multifocally. The trigger leading to SRMA still remains an unsolved riddle for immunologists and clinical neurologists. In the past, many attempts have been made to clarify the etiology of this disease without success. The purpose of writing this narrative review about SRMA is to summarize new insights on the pathogenesis of SRMA with a focus on immunologic dysregulation. Furthermore, unusual manifestations of the disease, new diagnostic approaches using possible laboratory biomarkers or diagnostic imaging tools, and potential innovative treatment strategies are discussed.
Topics: Animals; Dogs; Meningitis; Arteritis; Biomarkers; Steroids; Dog Diseases
PubMed: 37704169
DOI: 10.1016/j.tvjl.2023.106030 -
Endocrinology and Metabolism (Seoul,... Aug 2023Adrenal incidentalomas represent an increasingly common clinical conundrum with significant implications for patients. The revised 2023 European Society of Endocrinology... (Review)
Review
Adrenal incidentalomas represent an increasingly common clinical conundrum with significant implications for patients. The revised 2023 European Society of Endocrinology (ESE) guideline incorporates cutting-edge evidence for managing adrenal incidentalomas. This paper provides a concise review of the updated contents of the revised guideline. In the 2023 guideline, in patients without signs and symptoms of overt Cushing's syndrome, a post-dexamethasone cortisol level above 50 nmol/L (>1.8 μg/dL) should be considered as mild autonomous cortisol secretion. Regarding the criteria of benign adrenal adenomas, a homogeneous adrenal mass with ≤10 Hounsfield units on non-contrast computed tomography requires no further follow-up, irrespective of its size. The updated guideline also discusses steroid metabolomics using tandem mass spectrometry to discriminate malignancy. It underscores the importance of high-volume surgeons performing adrenalectomy and emphasizes the pivotal role of a multidisciplinary team approach in deciding the treatment plan for indeterminate adrenal masses. The guideline advocates for more proactive surgical treatment for indeterminate adrenal masses in young patients (<40 years) and pregnant women. This review of the 2023 ESE guideline underscores the ongoing evolution of the adrenal incidentaloma management landscape, emphasizing the need for further research and adaptation of diagnostic and therapeutic strategies.
Topics: Pregnancy; Humans; Female; Adrenal Gland Neoplasms; Hydrocortisone; Cushing Syndrome; Adrenalectomy
PubMed: 37583083
DOI: 10.3803/EnM.2023.1779 -
Journal of Clinical Lipidology 2023Lifestyle habits can have a profound impact on atherosclerotic cardiovascular disease (ASCVD) risk. The National Lipid Association previously published recommendations... (Review)
Review
Lifestyle habits can have a profound impact on atherosclerotic cardiovascular disease (ASCVD) risk. The National Lipid Association previously published recommendations for lifestyle therapies to manage dyslipidemia. This Clinical Perspective provides an update with a focus on nutrition interventions for the three most common dyslipidemias in adults: 1) low-density lipoprotein cholesterol (LDL-C) elevation; 2) triglyceride (TG) elevation, including severe hypertriglyceridemia with chylomicronemia; and 3) combined dyslipidemia, with elevations in both LDL-C and TG levels. Lowering LDL-C and non-high-density lipoprotein cholesterol are the primary objectives for reducing ASCVD risk. With severe TG elevation (≥500 mg/dL), the primary objective is to prevent pancreatitis and ASCVD risk reduction is secondary. Nutrition interventions that lower LDL-C levels include reducing cholesterol-raising fatty acids and dietary cholesterol, as well as increasing intakes of unsaturated fatty acids, plant proteins, viscous fibers, and reducing adiposity for patients with overweight or obesity. Selected dietary supplements may be employed as dietary adjuncts. Nutrition interventions for all patients with elevated TG levels include restricting intakes of alcohol, added sugars, and refined starches. Additional lifestyle factors that reduce TG levels are participating in daily physical activity and reducing adiposity in patients with overweight or obesity. For patients with severe hypertriglyceridemia, an individualized approach is essential. Nutrition interventions for addressing concurrent elevations in LDL-C and TG include a combination of the strategies described for lowering LDL-C and TG. A multidisciplinary approach is recommended to facilitate success in making and sustaining dietary changes and the assistance of a registered dietitian nutritionist is highly recommended.
Topics: Humans; Adult; Cholesterol, LDL; Overweight; Cholesterol; Dyslipidemias; Triglycerides; Hyperlipidemias; Atherosclerosis; Hypertriglyceridemia; Obesity
PubMed: 37271600
DOI: 10.1016/j.jacl.2023.05.099 -
Cell Metabolism Jul 2023Glucose dependency of cancer cells can be targeted with a high-fat, low-carbohydrate ketogenic diet (KD). However, in IL-6-producing cancers, suppression of the hepatic...
Glucose dependency of cancer cells can be targeted with a high-fat, low-carbohydrate ketogenic diet (KD). However, in IL-6-producing cancers, suppression of the hepatic ketogenic potential hinders the utilization of KD as energy for the organism. In IL-6-associated murine models of cancer cachexia, we describe delayed tumor growth but accelerated cachexia onset and shortened survival in mice fed KD. Mechanistically, this uncoupling is a consequence of the biochemical interaction of two NADPH-dependent pathways. Within the tumor, increased lipid peroxidation and, consequently, saturation of the glutathione (GSH) system lead to the ferroptotic death of cancer cells. Systemically, redox imbalance and NADPH depletion impair corticosterone biosynthesis. Administration of dexamethasone, a potent glucocorticoid, increases food intake, normalizes glucose levels and utilization of nutritional substrates, delays cachexia onset, and extends the survival of tumor-bearing mice fed KD while preserving reduced tumor growth. Our study emphasizes the need to investigate the effects of systemic interventions on both the tumor and the host to accurately assess therapeutic potential. These findings may be relevant to clinical research efforts that investigate nutritional interventions such as KD in patients with cancer.
Topics: Mice; Animals; Diet, Ketogenic; Cachexia; Corticosterone; Interleukin-6; Ferroptosis; NADP; Ketone Bodies; Glucose; Neoplasms
PubMed: 37311455
DOI: 10.1016/j.cmet.2023.05.008 -
Journal of Cutaneous Medicine and... 2023Hand eczema is a chronic condition that affects an estimated 14.5% of the general population. It has severe quality of life ramifications in those that struggle with it,... (Review)
Review
Hand eczema is a chronic condition that affects an estimated 14.5% of the general population. It has severe quality of life ramifications in those that struggle with it, including days missed from work or school, productivity loss and impaired work functioning. For years, the standard of care included topical moisturizing creams, topical steroids and more recently systemic agents. As new therapeutic targets emerge and recent advances are being developed, it is now more possible than ever that hand eczema can be managed via the underlying mechanisms. A review of the literature was conducted to identify current treatment options for hand eczema and chronic hand eczema. The terms 'hand eczema', 'hand dermatitis' were used to search PubMed, CENTRAL and Embase. To identify new therapies still undergoing investigation, we used the terms 'hand eczema', 'hand dermatitis', 'atopic dermatitis', and 'vesicular eczema of hands and/or feet' to search Clinicaltrials.gov for all studies until December 2022. There were 56 ongoing clinical trials identified for pharmacological treatments for hand eczema on Clinicaltrials.gov from 2000 - 2022, with 16 that are new or ongoing. These included studies for dupilumab, ruxolitinib, delgocitinib (LEO124249), gusacitinib (ASN002), AFX 5931, and roflumilast (ARQ-252). Two major classes of drugs emerging for the treatment of hand eczema include IL-4/IL-13 inhibitors and JAK inhibitors. With the increase in efficacy seen with these new drugs, we are also noting improved adverse effect profiles, making them attractive options to add to a clinician's management toolbox for patients with hand eczema.
Topics: Humans; Quality of Life; Eczema; Dermatitis, Atopic; Hand; Steroids; Treatment Outcome
PubMed: 37496489
DOI: 10.1177/12034754231188325 -
Journal of Crohn's & Colitis Dec 2023Acute severe ulcerative colitis [ASUC] is a medical emergency treated with intravenous steroids followed by infliximab or cyclosporin in the case of steroid failure with...
BACKGROUND AND AIMS
Acute severe ulcerative colitis [ASUC] is a medical emergency treated with intravenous steroids followed by infliximab or cyclosporin in the case of steroid failure with emergent colectomy required in refractory or severe cases. Case series have reported on the effectiveness of tofacitinib for refractory disease, but data regarding the effectiveness of upadacitinib in this setting have not been previously reported. We describe the use of upadacitinib therapy for steroid-refractory ASUC in patients with prior loss of response to infliximab.
METHODS
Six patients who received upadacitinib for steroid-refractory ASUC were identified at two Australian tertiary inflammatory bowel disease centres. Patients were followed for up to 16 weeks after discharge with clinical, biochemical and intestinal ultrasound [IUS] outcomes.
RESULTS
All six patients demonstrated clinical response to upadacitinib induction during their inpatient admission. Four patients achieved corticosteroid-free clinical remission by week 8, including complete resolution of rectal bleeding and transmural healing assessed by IUS, and sustained clinical remission at week 16. One patient proceeded to colectomy at week 15 due to refractory disease. No adverse events directly attributable to upadacitinib were identified.
CONCLUSIONS
Upadacitinib may have a role as a safe and effective salvage therapy for steroid-refractory ASUC in patients who have previously failed to respond to infliximab therapy. Prospective studies are required to determine the safety and efficacy of upadacitinib use in this setting before routine use can be recommended.
Topics: Humans; Infliximab; Colitis, Ulcerative; Salvage Therapy; Treatment Outcome; Australia; Steroids; Colectomy; Retrospective Studies; Heterocyclic Compounds, 3-Ring
PubMed: 37422724
DOI: 10.1093/ecco-jcc/jjad115 -
Frontiers in Immunology 2023Autoimmune hemolytic anemia (AIHA) is an acquired hemolytic disorder, mediated by auto-antibodies, and has a variable clinical course ranging from fully compensated low... (Review)
Review
Autoimmune hemolytic anemia (AIHA) is an acquired hemolytic disorder, mediated by auto-antibodies, and has a variable clinical course ranging from fully compensated low grade hemolysis to severe life-threatening cases. The rarity, heterogeneity and incomplete understanding of severe AIHA complicate the recognition and management of severe cases. In this review, we describe how severe AIHA can be defined and what is currently known of the severity and outcome of AIHA. There are no validated predictors for severe clinical course, but certain risk factors for poor outcomes (hospitalisation, transfusion need and mortality) can aid in recognizing severe cases. Some serological subtypes of AIHA (warm AIHA with complement positive DAT, mixed, atypical) are associated with lower hemoglobin levels, higher transfusion need and mortality. Currently, there is no evidence-based therapeutic approach for severe AIHA. We provide a general approach for the management of severe AIHA patients, incorporating monitoring, supportive measures and therapeutic options based on expert opinion. In cases where steroids fail, there is a lack of rapidly effective therapeutic options. In this era, numerous novel therapies are emerging for AIHA, including novel complement inhibitors, such as sutimlimab. Their potential in severe AIHA is discussed. Future research efforts are needed to gain a clearer picture of severe AIHA and develop prediction models for severe disease course. It is crucial to incorporate not only clinical characteristics but also biomarkers that are associated with pathophysiological differences and severity, to enhance the accuracy of prediction models and facilitate the selection of the optimal therapeutic approach. Future clinical trials should prioritize the inclusion of severe AIHA patients, particularly in the quest for rapidly acting novel agents.
Topics: Humans; Anemia, Hemolytic, Autoimmune; Hemolysis; Steroids; Blood Transfusion; Disease Progression
PubMed: 37795092
DOI: 10.3389/fimmu.2023.1228142 -
United European Gastroenterology Journal Oct 2023Acute severe ulcerative colitis (ASUC) occurs in up to 25% of patients with ulcerative colitis (UC). Therapeutic approaches have evolved during the past years with the... (Review)
Review
Acute severe ulcerative colitis (ASUC) occurs in up to 25% of patients with ulcerative colitis (UC). Therapeutic approaches have evolved during the past years with the increasing bio exposure of admitted patients and the extension of the number of approved drugs for UC. In this review, we aimed to summarize the latest evidence in short-term and long-term medical strategies for ASUC. In addition to general principles such as venous thromboembolism prophylaxis, screening for triggering and worsening factors and close monitoring, first-line therapy for ASUC remains intravenous corticosteroids. In naive patients, the optimum maintenance strategy for steroid-responding patients does not necessarily include biologics. Second-line therapy includes infliximab or calcineurin inhibitors (CNIs) with similar short- and long-term colectomy rates. Despite its pathophysiological relevance, there is insufficient evidence to promote intensified induction with infliximab. Prior treatment exposure is a cornerstone for guiding therapeutic choice of short- and long-term therapies in the context of ASUC: in anti-TNF exposed patients, CNIs may be favored as a bridge therapy to vedolizumab or ustekinumab. Third-line salvage therapy could be a therapeutic option in selected patients referred to expert centers. Additionally, evidence is accumulating regarding the use of tofacitinib in ASUC.
Topics: Humans; Colitis, Ulcerative; Infliximab; Tumor Necrosis Factor Inhibitors; Treatment Outcome; Steroids
PubMed: 37475143
DOI: 10.1002/ueg2.12442 -
Journal of the American Heart... Jun 2023Management of elevated low-density lipoprotein cholesterol (LDL-C) is central to preventing atherosclerotic cardiovascular disease (ASCVD) and key to reducing the risk... (Review)
Review
Management of elevated low-density lipoprotein cholesterol (LDL-C) is central to preventing atherosclerotic cardiovascular disease (ASCVD) and key to reducing the risk of ASCVD events. Current guidelines on the management of blood cholesterol recommend statins as first-line therapy for LDL-C reduction according to an individual's ASCVD risk and baseline LDL-C levels. The addition of nonstatin lipid-lowering therapy to statins to achieve intensive LDL-C lowering is recommended for patients at very high risk of ASCVD events, including patients with familial hypercholesterolemia who have not achieved adequate LDL-C lowering with statins alone. Despite guideline recommendations and clinical trial evidence to support the use of lipid-lowering therapies for ASCVD risk reduction, most patients at high or very high risk do not meet LDL-C thresholds. This review explores the challenges associated with LDL-C lowering in contemporary clinical practice and proposes a framework for rethinking the binary definition of ASCVD, shifting from "primary" versus "secondary" prevention to a "continuum of risk." The approach considers the role of plaque burden and progression in subclinical disease and emphasizes the importance of early risk assessment and treatment for preventing first cardiovascular events. Patients at high risk of ASCVD events who require significant LDL-C lowering should be considered for combination therapies comprising statin and nonstatin agents. Practical guidance for the pharmacological management of elevated LDL-C, both now and in the future, is provided.
Topics: Humans; Cholesterol, LDL; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cardiovascular Diseases; Cholesterol; Atherosclerosis
PubMed: 37260036
DOI: 10.1161/JAHA.122.028892 -
Human Reproduction Update Nov 2023Estrogens regulate disparate female physiological processes, thus ensuring reproduction. Altered estrogen levels and signaling have been associated with increased risks... (Review)
Review
The pathophysiological role of estrogens in the initial stages of pregnancy: molecular mechanisms and clinical implications for pregnancy outcome from the periconceptional period to end of the first trimester.
BACKGROUND
Estrogens regulate disparate female physiological processes, thus ensuring reproduction. Altered estrogen levels and signaling have been associated with increased risks of pregnancy failure and complications, including hypertensive disorders and low birthweight babies. However, the role of estrogens in the periconceptional period and early pregnancy is still understudied.
OBJECTIVE AND RATIONALE
This review aims to summarize the current evidence on the role of maternal estrogens during the periconceptional period and the first trimester of pregnancies conceived naturally and following ART. Detailed molecular mechanisms and related clinical impacts are extensively described.
SEARCH METHODS
Data for this narrative review were independently identified by seven researchers on Pubmed and Embase databases. The following keywords were selected: 'estrogens' OR 'estrogen level(s)' OR 'serum estradiol' OR 'estradiol/estrogen concentration', AND 'early pregnancy' OR 'first trimester of pregnancy' OR 'preconceptional period' OR 'ART' OR 'In Vitro Fertilization (IVF)' OR 'Embryo Transfer' OR 'Frozen Embryo Transfer' OR 'oocyte donation' OR 'egg donation' OR 'miscarriage' OR 'pregnancy outcome' OR 'endometrium'.
OUTCOMES
During the periconceptional period (defined here as the critical time window starting 1 month before conception), estrogens play a crucial role in endometrial receptivity, through the activation of paracrine/autocrine signaling. A derailed estrogenic milieu within this period seems to be detrimental both in natural and ART-conceived pregnancies. Low estrogen levels are associated with non-conception cycles in natural pregnancies. On the other hand, excessive supraphysiologic estrogen concentrations at time of the LH peak correlate with lower live birth rates and higher risks of pregnancy complications. In early pregnancy, estrogen plays a massive role in placentation mainly by modulating angiogenic factor expression-and in the development of an immune-tolerant uterine micro-environment by remodeling the function of uterine natural killer and T-helper cells. Lower estrogen levels are thought to trigger abnormal placentation in naturally conceived pregnancies, whereas an estrogen excess seems to worsen pregnancy development and outcomes.
WIDER IMPLICATIONS
Most current evidence available endorses a relation between periconceptional and first trimester estrogen levels and pregnancy outcomes, further depicting an optimal concentration range to optimize pregnancy success. However, how estrogens co-operate with other factors in order to maintain a fine balance between local tolerance towards the developing fetus and immune responses to pathogens remains elusive. Further studies are highly warranted, also aiming to identify the determinants of estrogen response and biomarkers for personalized estrogen administration regimens in ART.
Topics: Pregnancy; Female; Humans; Pregnancy Outcome; Estrogens; Pregnancy Trimester, First; Placentation; Fertilization in Vitro; Estradiol
PubMed: 37353909
DOI: 10.1093/humupd/dmad016