Systemic sclerosis (SSc) is a multisystem disease characterized by functional and structural abnormalities of small blood vessels, fibrosis of the skin and internal organs, immune system activation, and autoimmunity. The gastrointestinal tract is involved in nearly all patients and is a source of significant morbidity and even mortality. The aim of this review is to summarize the pathogenesis and to provide a clinical approach to these patients.
Inflammation induced by toxins, micro-organisms, or autoimmunity may result in pathogenic fibrosis, leading to long-term tissue dysfunction, morbidity, and mortality. Immune cells play a role in both induction and resolution of fibrosis. γδ T cells are an important group of unconventional T cells characterized by their expression of non-major histocompatibility complex restricted clonotypic T cell receptors for non-peptide antigens. Accumulating evidence suggests that subsets of γδ T cells in experimentally induced fibrosis following bleomycin treatment, or infection with Bacillus subtilis, play pro-inflammatory roles that instigate fibrosis, whereas the same cells may also play a role in resolving fibrosis. These processes appear to be linked at least in part to the cytokines produced by the cells at various stages, with interleukin (IL)-17 playing a central role in the inflammatory phase driving fibrosis, but later secretion of IL-22, interferon γ, and CXCL10 preventing pathologic fibrosis. Moreover, γδ T cells appear to be involved, in an antigen-driven manner, in the prototypic human fibrotic disease, systemic sclerosis (SSc). In this paper we review in brief the scientific publications that have implicated γδ T cells in fibrotic diseases and their pro- and anti-fibrotic effects.
To the Editor, Dr Nair’s letter to the editor regarding the failed nerve blocks mentioned in our paper, “Comparison of the supraclavicular, infraclavicular and axillary approaches for ultrasound-guided brachial plexus block for surgical anesthesia”,1 raised several points that I believe are worth looking at in more detail. We are grateful for Dr Nair’s comments which have contributed to the furthering of scholarly discourse.
In general, Dr Nair’s letter relates to the blocks that our research classified as failed. He then discusses various approaches and suggests the reason for the failures of the axillary approach blocks.
For the purpose of reducing maternal and neonatal morbidity, elective single transfer (eSET) in in vitro fertilization (IVF) was first proposed in 1999. The purpose of this review is to summarize recent oral debate between a proponent and an opponent of expanded eSET utilization in an attempt to determine whether a blanket eSET policy, as is increasingly considered, is defensible. While eSET is preferable when possible, and agreed upon by provider and patient, selective double embryo transfer (DET) must be seriously entertained if deemed more appropriate or is desired by the patient. Patient autonomy, let alone prolonged infertility and advancing age, demand nothing less. Importantly, IVF-generated twins represent only 15.7% of the national twin birth rate in the United States. Non-IVF fertility treatments have been identified as the main cause of all multiple births for quite some time. However, educational and regulatory efforts over the last decade, paradoxically, have exclusively only been directed at the practice of IVF, although IVF patient populations are rapidly aging. It is difficult to understand why non-IVF fertility treatments, usually applied to younger women, have so far escaped attention. This debate on eSET utilization in association with IVF may contribute to a redirection of priorities.
Objective: To examine the relationship between duration of fetal hypoxia, nucleated red blood cell (NRBC) count, and fetal growth.
Methods: Pregnant rats were exposed to a severe hypoxia (9.5%–10% O2) for varying time intervals (2, 6, 12, 24, 48, and 120 hours; n=4 for each time interval) immediately prior to delivery at term. Normoxic controls were exposed to room air (21% O2) and matched for all other study variables (n=4 rats for each time interval). Pups were delivered via hysterotomy while maintaining exposure gas concentrations. Blood gas analysis and NRBC counts were performed, and fetal body and liver weights were recorded. Student’s t test and simple regression were used for statistical analysis.
Results: As the duration of hypoxia increased, fetal weight, liver weight, blood bicarbonate, and base excess levels decreased significantly; concomitantly, NRBC counts increased. This increase in NRBCs became statistically significant after 24 hours of exposure. After 48 hours of hypoxia there was a 2.5-fold rise in NRBC count, and after 120 hours of hypoxia there was a 4.5-fold rise in NRBC count over control levels. After 12 or more hours of hypoxia, fetal body weights were significantly reduced; 120 hours of hypoxia resulted in a 35% reduction in fetal body weight, a 34% reduction in fetal liver weight, and 356% increase in NRBC count.
Conclusion: In a pregnant rat model, chronic maternal hypoxia (≥24 hours) results in a significant increase in fetal NRBC counts as well as reduced fetal body weight and organ growth.
Introduction: The primary non-pharmacological management recommended for patients with osteoporosis (OP) is exercise, but whether it should be high-force, resistive, or other means can be obscure.
Objective: To describe the role of exercises in osteoporotic fracture prevention, identify effects and potential risks of high-force exercises, detect the optimal exercises to combat OP, and explore the challenges that might arise from interventions.
Methods: A search on MEDLINE and Cochrane databases was conducted on the role of exercises in preventing osteoporotic fractures from 1989 onwards, leading to 40 results, including op-ed pieces, qualitative studies, randomized clinical trials (RCTs) (n=5), and RCT follow-up studies (n=1). Articles deemed relevant to the objectives were analyzed and summarized. Data on effects of vitamin D and calcium supplementation were later gathered from different sources as well.
Results: High-intensity, resistive strength training provided the maximum benefit in increasing bone mineral density (BMD) levels, muscle mass, and reduction in fractures, while posture and balance exercises only improved mobility. High-force exercises did not increase fractures and were associated with increases in BMD. Interventions including exercises, vitamin D, and calcium intake had limited effect when used as single interventions, while vitamin D and calcium may potentially cause increases of cardiovascular events.
Conclusion: A long-term regular exercise program designed to improve postural stability, mobility, and mechanical efficiency, alongside an increased vitamin D and dietary calcium intake, is most effective in preventing OP and reducing osteoporotic fractures.
A growing body of evidence implicates that maternal inflammation during pregnancy is associated with increased risk of neurodevelopmental disorders in the offspring. The pathophysiological mechanisms by which maternal inflammation evokes fetal brain injury and contribute to long-term adverse neurological outcomes are not completely understood. In this review, we summarize our 10 years’ research experience on maternal inflammation and the implications upon the fetal/offspring brain. We review our findings regarding the underlying mechanisms that connects maternal inflammation and fetal brain injuries (e.g. cytokines, oxidative stress), we discuss our imaging, pathological and behavioral test results which support brain damage following maternal inflammation and finally we describe some of the therapeutic strategies which might prevent the damage.
The changing science of the urinary microbiota and microbiome has both clinical and research implications. This review manuscript provides an overview of the state of this science, as well as a discussion of the potential for prevention, diagnosis, and treatment of human disease. The history of techniques used for clinical detection of infection are placed into context along with the modern methods of bacterial detection and identification.
To evaluate the decrease in luteinizing hormone (LH) levels following gonadotropin-releasing hormone (GnRH) antagonist administration in in vitro fertilization (IVF) cycles, data were retrospectively collected from 305 consecutive IVF or intracytoplasmic sperm injection (ICSI) cycles of patients who underwent ovarian stimulation with gonadotropins and were treated with GnRH antagonist for the prevention of premature luteinization. We compared the percent change in LH concentration from stimulation start to that observed before ovulation triggering in patients with or without anovulation. Anovulatory patients were younger, with higher body mass index (BMI), and demonstrated higher ovarian reserve parameters as compared to ovulatory patients. The decline in LH concentration was almost two-fold greater in anovulatory versus ovulatory patients. Numbers of oocytes, fertilizations, cleavage stage embryos, and transferred embryos were similar; however, implantation rates were higher in anovulatory versus ovulatory patients. Older patients (age ≥39) showed a smaller decline in LH levels as compared to younger ones (age <39) and exhibited poor IVF outcomes. There is a wide range of pituitary responses to GnRH antagonists. Anovulatory patients are more susceptible to GnRH antagonists and therefore demonstrate over-suppression of the pituitary. Older patients demonstrate a reduced pituitary response to GnRH antagonists than younger ones. Cycle scheduling with estradiol pretreatment did not influence LH decline, nor IVF treatment outcomes.
Thyroid hormone replacement therapy in patients following thyroidectomy for thyroid cancer, although a potentially straightforward clinical problem, can present the clinician and patient with a variety of challenges. Most often the problems are related to the dose and preparation of thyroid hormone (TH) to use. Some patients feel less well following thyroidectomy and/or radioiodine ablation than they did before their diagnosis. We present evidence that levothyroxine (L-T4) is the preparation of choice, and keeping the thyroid-stimulating hormone (TSH) between detectable and 0.1 mU/L should be the standard of care in most cases. In unusual circumstances, when the patient remains clinically hypothyroid despite a suppressed TSH, we acknowledge there may be as yet unidentified factors influencing the body’s response to TH, and individualized therapy may be necessary in such patients.
