Non-surgical management of thyroid nodules – the role of ablative therapies

Context After a thorough evaluation most thyroid nodules are deemed of no clinical consequence and can be observed. However, when they are compressive, toxic, or involved by papillary thyroid carcinoma (PTC) surgery or RAI (if toxic) are the treatments of choice. Both interventions can lead to hypothyroidism and other adverse outcomes (e.g. scar, dysphonia, logistical limitation with RAI). Active surveillance might be used for papillary thyroid microcarcinoma (PTMC) initially, but anxiety leads many cases to surgery later. Several ablative therapies have thus evolved over the last few years aimed at treating these nodules while avoiding described risks. Cases We present 4 cases of thyroid lesions causing concerns (compressive symptoms, thyrotoxicosis, anxiety with active surveillance of PTMC). The common denominator is patients’ attempt to preserve thyroid function, bringing into focus percutaneous ethanol injection (PEI) and thermal ablation techniques (radiofrequency ablation – RFA – being the most common). We discuss the evidence supporting these approaches and compare them with standard therapy, where evidence exists. We discuss additional considerations for the utilization of these therapies, their side-effects and conclude with a simplified description of how these procedures are performed. Conclusions Thermal ablation, particularly RFA, is becoming an attractive option for managing a subgroup of solid thyroid nodules while PEI has a role in managing thyroid cysts and a select group of PTMC. Their role in the algorithm of thyroid nodule management is still being refined and technical expertise will be essential to reproduce the reported results into everyday practice.

Obesity-Related Metabolic Dysfunction in Dairy Cows and Horses: Comparison to Human Metabolic Syndrome

Obesity has become a serious health problem with frequent occurrence both in human and animal populations. It is estimated that it may affect over 85% of the human population and 70–80% of horses and cows by 2030. Fat cow syndrome (FCS) is a combination of metabolic, digestive, infectious, and reproductive disorders that affects obese periparturient dairy cows, and occurs most frequently in loose-housing systems, where periparturient and dry cows are fed and managed in one group disregarding the lactation stages. Equine metabolic syndrome (EMS) was named after human metabolic syndrome (MetS) and has insulin dysregulation as a central and consistent feature. It is often associated with obesity, although EMS may occur in a lean phenotype as well. Other inconsistent features of EMS are cardiovascular changes and adipose dysregulation. Laminitis is the main clinical consequence of EMS. MetS holds a 30-years old lead in research and represents a clustering of risk factors that comprise abdominal obesity, dyslipidemia, hypertension, and hyperglycemia (impaired fasting glucose or type 2 diabetes mellitus—T2DM), which are associated with doubled atherosclerotic cardiovascular disease risk, and a 5-fold increased risk for T2DM. The main aim of this review is to provide critical information for better understanding of the underlying mechanisms of obesity-related metabolic dysfunction in animals, especially in cows and horses, in comparison with MetS. Human medicine studies can offer suitable candidate mechanisms to fill the existing gap in the literature, which might be indispensable for owners to tackle FCS, EMS, and their consequences.

Understanding the interaction between cytomegalovirus and tuberculosis in children: The way forward

Over 1 million children develop tuberculosis (TB) each year, with a quarter dying. Multiple factors impact the risk of a child being exposed to Mycobacterium tuberculosis (Mtb), the risk of progressing to TB disease, and the risk of dying. However, an emerging body of evidence suggests that coinfection with cytomegalovirus (CMV), a ubiquitous herpes virus, impacts the host response to Mtb, potentially influencing the probability of disease progression, type of TB disease, performance of TB diagnostics, and disease outcome. It is also likely that infection with Mtb impacts CMV pathogenesis. Our current understanding of the burden of these 2 diseases in children, their immunological interactions, and the clinical consequence of coinfection is incomplete. It is also unclear how potential interventions might affect disease progression and outcome for TB or CMV. This article reviews the epidemiological, clinical, and immunological literature on CMV and TB in children and explores how the 2 pathogens interact, while also considering the impact of HIV on this relationship. It outlines areas of research uncertainty and makes practical suggestions as to potential studies that might address these gaps. Current research is hampered by inconsistent definitions, study designs, and laboratory practices, and more consistency and collaboration between researchers would lead to greater clarity. The ambitious targets outlined in the World Health Organization End TB Strategy will only be met through a better understanding of all aspects of child TB, including the substantial impact of coinfections.

Vitamin D related genetic polymorphisms affect serological response to high-dose vitamin D supplementation in multiple sclerosis

Introduction A poor 25-hydroxyvitamin D (25(OH)D) status is a much replicated risk factor for developing multiple sclerosis (MS), and several vitamin D-associated single nucleotide polymorphisms (SNPs) have been associated with a higher risk of MS. However, studies on the benefit of vitamin D supplementation in MS show inconclusive results. Here, we explore whether vitamin D-associated SNPs and MS risk alleles confound serological response to vitamin D supplementation. Methods 34 participants from the SOLARIUM study consented to genotyping, of which 26 had vitamin D data available. The SOLARIUM study randomised relapsing-remitting MS patients to placebo or 14,000 IU vitamin D3 for 48 weeks. Participants were categorised as either ‘carriers’ or ‘non-carriers’ of the risk allele for 4 SNPs: two related to D binding protein (DBP) and associated with lower 25(OH)D levels (rs4588 and rs7041), and two related to vitamin D metabolism enzymes CYP27B1 and CYP24A1 and associated with a higher risk of MS (rs12368653; rs2248359, respectively). 25(OH)D levels were determined at baseline and after 48 weeks. Results The DBP-related SNPs showed no difference in 25(OH)D status at baseline, but carriers of the rs7041 risk allele showed lower 25(OH)D-levels compared to non-carriers after 48 weeks of supplementation (median 224.2 vs. 332.0 nmol/L, p = 0.013). For CYP related SNPs, neither showed a difference at baseline, but carriers of the rs12368653 risk allele showed higher 25(OH)D-levels compared to non-carriers after 48 weeks of supplementation (median 304.1 vs. 152.0 nmol/L, p = 0.014). Discussion Vitamin D-related SNPs affect the serological response to high-dose vitamin D supplementation. The effects on more common doses of vitamin D, as well as the clinical consequence of this altered response, need to be investigated further.

Motorized Spiral Enteroscopy: to infinity and beyond?

With the advent of device-assisted enteroscopy (DAE) in the early 2000s, endoscopic access to the entire small bowel is possible nowadays (1). And yet, there is still room for improvement. Total enteroscopy remains a time-consuming procedure, often combining the antegrade (oral) and retrograde (anal) approach with only a reasonable chance to obtain complete endoscopy of the entire small bowel (2). Therefore, the aim is to go faster, deeper and to perform more advanced therapeutic interventions within the long and tortuous small bowel. Moreover, DAE was also shown to be effective to perform endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy and to complete colonoscopy in patients with previously incomplete conventional colonoscopy due to long dolichocolon (3). The latest DAE development is Motorized Spiral Enteroscopy (MSE), initially conceptualized as a manually driven rotational spiral overtube by Paul A. Akerman, and further developed and commercialized as a motorized spiral overtube by the Olympus Medical Systems Corporation (4). Initial feasibility trials have shown that MSE can compete with already available DAE techniques (single- and double-balloon enteroscopy) with regard to diagnostic yield and endotherapy within the small bowel (5,6). However, being a short type enteroscope of 168 cm (as compared to the 200 cm long single- and double-balloon enteroscopes), MSE appears to be even more effective in obtaining deep and total enteroscopy with a relatively short procedural duration (2,6). In addition, the working channel diameter is increased to 3.2 mm (as compared to 2.8 mm) with an extra irrigation channel, facilitating therapeutic interventions within the small bowel. This faster and deeper (but more aggressive) enteroscopy technique comes with the price of an increased risk of mucosal injuries (ranging from superficial bruising to laceration and even perforation) within the oesophagus and the small bowel, luckily remaining asymptomatic most of the time without any clinical consequence (6). So far, this promising new technique has the potential of becoming a gamechanger in the still evolving field of deep enteroscopy.

Herb-drug interactions in neuropsychiatric pharmacotherapy – a review of clinically relevant findings

: The management of neuropsychiatric disorders relies heavily on pharmacotherapy. The use of herbal products as complimentary medicine, often concomitantly, is common among patients taking prescription neuropsychiatric drugs. Herb-drug interaction, a clinical consequence of this practice, may jeopardize the success of pharmacotherapy in neuropsychiatry. Besides the well-known ability of phytochemicals to inhibit and/or induce drug-metabolizing enzymes and transport proteins, several phytoconstituents are capable of exerting pharmacological effects on the central nervous system. The consequent pharmacokinetic and pharmacodynamic interactions with orthodox medications often result in deleterious clinical consequences. This study reviewed the relevant literature and identified 13 commonly used herbal products – celery, echinacea, ginkgo, ginseng, hydroxycut, kava, kratom, moringa, piperine, rhodiola, St John’s wort, terminalia/commiphora ayurvedic mixture and valerian – which have shown clinically relevant interactions with prescription drugs used in the management of neuropsychiatric disorders. The clinical focus is aimed to provide easily accessible information that will be of interest to clinicians, researchers, and the drug-consuming public.

In Vitro Cell Toxicity and Intracellular Uptake of Doxorubicin Exposed as a Solution or Liposomes: Implications for Treatment of Hepatocellular Carcinoma

Cytostatic effects of doxorubicin in clinically applied doses are often inadequate and limited by systemic toxicity. The main objective of this in vitro study was to determine the anti-tumoral effect (IC50) and intracellular accumulation of free and liposomal doxorubicin (DOX) in four human cancer cell lines (HepG2, Huh7, SNU449 and MCF7). The results of this study showed a correlation between longer DOX exposure time and lower IC50 values, which can be attributed to an increased cellular uptake and intracellular exposure of DOX, ultimately leading to cell death. We found that the total intracellular concentrations of DOX were a median value of 230 times higher than the exposure concentrations after exposure to free DOX. The intracellular uptake of DOX from solution was at least 10 times higher than from liposomal formulation. A physiologically based pharmacokinetic model was developed to translate these novel quantitative findings to a clinical context and to simulate clinically relevant drug concentration–time curves. This showed that a liver tumor resembling the liver cancer cell line SNU449, the most resistant cell line in this study, would not reach therapeutic exposure at a standard clinical parenteral dose of doxorubicin (50 mg/m2), which is serious limitation for this drug. This study emphasizes the importance of in-vitro to in-vivo translations in the assessment of clinical consequence of experimental findings.

Tocilizumab-associated posterior reversible encephalopathy syndrome in giant-cell arteritis – case report

Backround We describe one of the first cases of a Posterior reversible encephalopathy syndrome (PRES) under tocilizumab as treatment of Giant cell arteritis (GCA). Case presentation A 65-year-old female with known GCA and treatment with Tocilizumab (TCZ) developed a convulsive epileptic seizure for the first time. MRI was suggestive of PRES and an associated left sided occipital hemorrhage. Extensive high blood pressure values were not detected. The patient recovered within a week and no further seizures occurred under anticonvulsive medication. Conclusion PRES during the treatment with Tocilizumab hasn’t been described in GCA so far. There are single reports of an association between TCZ and PRES in other entities. Thus, a link between interleukin-6 and the integrity of the vasculature could be considered. The clinical consequence should be a stringent blood pressure monitoring in the ambulant setting of patients receiving TCZ.