Waking Up to Monkeypox in the Midst of COVID-19.

The first incidence of the monkeypox virus (MPXV) was reported in a Danish research facility. Even though first discovered in monkeys, rodents account for the largest reservoir of the disease. It is an encapsulated, brick-shaped double-stranded DNA virus strongly related to the smallpox virus. The risk of acquiring MPXV has been found to be inversely related to smallpox vaccination. Although the cases were initially restricted to African countries, they were first reported outside Africa in the early 2000s. MPXV is transmitted through close personal contact, most commonly through direct skin-skin contact. The fatality rates associated with the MPXV tend to vary in different regions, with Congo clad basin having the highest mortality rate. The majority of the cases of MPXV have been reported in men who have sex with men. Although optimal infection control and treatment strategies are under investigation, the current management focus is on immunization and the isolation of patients. Effective control strategies are based on implementing a method of contact tracing, quarantining exposed and infected individuals, and using vaccines. There is no proven cure for MPXV, and most infected patients recover without medical intervention. Extensive studies are being conducted to determine the efficacy of antivirals in managing MPXV, with tecovirimat being the first antiviral medication approved by the Food and Drug Administration (FDA) to manage MPXV. The smallpox vaccine has traditionally been thought of as the most effective method of controlling the infection, possibly due to the similarities between the two viruses. However, numerous obstacles prevent the effective control of MPXV, including social isolation and stigma, poor understanding of the disease dynamics, lack of adequate patient education, and public health strategies.

The Role of Diet and Gut Microbiome in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic demyelinating condition of the central nervous system (CNS) characterized by immune-mediated damage to the myelin sheath of nerve cells. Genetic and environmental factors are believed to play a significant role. Unfortunately, the knowledge of therapeutic modalities in MS remains very limited, necessitating the need for novel therapeutic strategies. In the previous decade, there has been an influx of studies on the gut microbiome and its link to various neurological conditions, including MS. Various diets may have favorable effects on the gut microflora and may significantly alter the progression and outcomes of MS. Thus, identifying the merits of various diets and modulating them according to the specific nutritional requirements of MS patients can go a long way toward slowing the progression of the disease. Nutritional interventions and the use of the gut microbiome as diagnostic and therapeutic modalities open a host of new possibilities regarding the disease. In this review, we investigate the role of diet and the gut microbiome in the progression of MS. The functions of the gut-brain axis, antioxidants, vitamins, obesity, and various diets are also covered in this article.

Central Retinal Artery Occlusion: Can We Effectively Manage This Ocular Emergency in a Hospital Setting?

Central retinal artery occlusion (CRAO) is an ophthalmological emergency characterized by partial or complete occlusion of the central retinal artery. It is the ocular equivalent of an ischemic cerebral stroke. Patients frequently present with a significant, abrupt, painless loss of vision in one eye, with only around 20% of those affected getting functional visual acuity restored in the affected eye. Despite more than 150 years of clinical research, no consensus has been achieved regarding the most effective method of treating CRAO. The efficacy of all proposed treatments is debatable, and many of them have ambiguous risk profiles that present particular diagnostic and management difficulties and cause variations in clinical practice. In certain circumstances, thrombolysis may be attempted as a treatment option. However, the evidence to support the general use of thrombolytics in treating acute CRAO remains elusive. It is known that the risk factors predisposing to other cardiovascular and cerebrovascular events are often present in CRAO. Accordingly, identifying patients at the highest risk of stroke and secondary prevention of ischemic events remains the primary focus of management. This review offers a summary of all the current treatment options available for managing CRAO, with particular reference to their limitations and inconsistent results found in relevant studies until 2022.

The Role of Mesenchymal Stem Cells in the Treatment of Type 1 Diabetes.

Type 1 diabetes (T1D) is a chronic disease characterized by inadequate or absent insulin production due to the autoimmune destruction of beta (ß) cells in the pancreas. It was once called "juvenile diabetes" since the disease frequently occurs in children, but it can also develop in adults. According to the International Diabetes Federation, an estimated 700 million adults will suffer from diabetes by 2045. Although the exact cause of diabetes remains unknown, it is hypothesized that genetic factors, environmental factors, and exposure to certain viruses play a role in the development of T1D. To date, exogenous insulin is the most common treatment for T1D. However, it is not a cure for the disease. Islet cell transplantation and pancreatic transplantation are two additional treatments that have gained popularity in recent years, but their clinical application may be limited by the need for high doses of immunosuppressants, the rarity of human cadaveric islets, and the need for extensive surgery in pancreatic transplantation. Mesenchymal stem cells (MSCs) are a highly promising novel treatment for T1D and their discovery has advanced biological sciences by allowing for modification of cell fate and the development of higher-order cellular structures. They play an essential role in lowering levels of fasting blood sugar, hemoglobin A1c, and C-peptide, and in treating microvascular complications associated with T1D. However, some of the disadvantages of its use in clinical practice are limited to its method of collection, proliferation rate, cell activity with age, and the risk of tumour formation identified in some studies. Large-scale studies are required to discover the mechanism of action of MSCs after administration as well as the optimal route, dose, and timing to maximize the benefits to patients. This article focuses primarily on the role of MSCs in the treatment of T1D and compares the feasibility, benefits, and drawbacks of MSCs in the treatment of T1D.

Therapeutic Efficacy of Botulinum Toxin in Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a unilateral, paroxysmal, sharp, shooting, or jabbing pain that occurs in the trigeminal nerve divisions, including the ophthalmic (V1), maxillary (V2), and mandibular (V3) nerves. Typically, an episode is triggered by anything touching the face or teeth. TN is a clinical diagnosis with no specific diagnostic test; it is determined by the patient's medical history and pain description. Imaging is necessary to exclude secondary causes. The precise reason for TN is uncertain, but it is commonly believed to result from vascular compression of the trigeminal nerve root, typically near its origin in the pons. There are numerous surgical and medical treatment options available. The most frequently applied medical treatment therapies are carbamazepine and oxcarbazepine. Surgical alternatives are reserved for patients who do not respond to medical treatment. Botulinum toxin A (BTX-A) has emerged as a novel and promising alternative to surgery for individuals whose pain is unresponsive to medication. Multiple studies have established the safety and usefulness of BTX-A in treating TN, with the most significant benefits occurring between six weeks and three months after the surgery. This article reviews various studies published in the last 10 years regarding the therapeutic use of BTX-A in TN. These studies include various observational, clinical, pilot, and animal studies.

Ethnical Disparities in Response to Edaravone in Patients With Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a progressive neurodegenerative disease characterized by the weakness of voluntary muscles due to the loss of motor neurons. Symptoms ultimately culminate in the form of respiratory failure due to the involvement of the diaphragm. Unfortunately, there is no known cure for this disease. Hence, supportive therapy is the only available option in most terminal cases. However, Riluzole and Edaravone (EDA) are the only two known drugs approved by the U.S. Food and Drug Administration (FDA) for treating this condition. In 2017, EDA was approved for the treatment of ALS. It is hypothesized that Riluzole and EDA work via a mechanism involving antioxidants, which nullifies the oxidative stress believed to be involved in ALS. However, most studies in several countries have found a wide range of disparities in the efficacy of this drug. In this review, we aim to summarize the differences in results from epidemiological studies across 10 different countries and hypothesize the potential causes of these differences.

A Comprehensive Review of Bradykinin-Induced Angioedema Versus Histamine-Induced Angioedema in the Emergency Department.

Angioedema (AE) is a condition that is frequently encountered in the emergency department (ED). It is a rare condition with localized, asymmetrical swelling of the skin and/or mucosa that is frequently nonpruritic and primarily affects locations with loose connective tissue. Physicians must have a thorough understanding of this condition since it can cause fatal airway compromise, which might be the presenting symptom. Histamine-mediated AE is the most common type of AE seen in EDs. However, ED physicians must be on the lookout for the less common bradykinin-mediated types of AE as these do not respond to the same therapy as histamine-mediated AE. Hospitals may lack specialized drugs or protocols, and many ED staff may be unable to identify or treat bradykinin-mediated AE. It is crucial to understand the pathophysiology of the various kinds of AE in order to optimize treatment. The goal of this review paper is to provide an overview of the pathophysiology, clinical manifestations, and treatment options for bradykinin and histamine-induced AE in the ED.

Ultrasonographic Halo Score in giant cell arteritis: association with intimal hyperplasia and ischaemic sight loss.

OBJECTIVES: We investigated the relationship between the ultrasonographic Halo Score and temporal artery biopsy (TAB) findings in GCA. METHODS: This is a prospective study including 90 patients suspected of having GCA. Ultrasonography of temporal/axillary arteries and a TAB were obtained in all patients at baseline. An experienced pathologist evaluated whether TAB findings were consistent with GCA, and whether transmural inflammation, giant cells and intimal hyperplasia were present. Ultrasonographic Halo Scores were determined. Receiver operating characteristic analysis was performed. RESULTS: Twenty-seven patients had a positive TAB, while 32 patients with a negative TAB received a clinical diagnosis of GCA after 6 months of follow-up. Patients with a positive TAB showed higher Halo Scores than patients with a negative TAB. The presence of intimal hyperplasia in the biopsy, rather than the presence of transmural inflammation or giant cells, was associated with elevated Halo Scores in patients with GCA. The Halo Score discriminated well between TAB-positive patients with and without intimal hyperplasia, as indicated by an area under the curve of 0.82 in the receiver operating characteristic analysis. Patients with a positive TAB and intimal hyperplasia more frequently presented with ocular ischaemia (40%) than the other patients with GCA (13-14%). CONCLUSION: The ultrasonographic Halo Score may help to identify a subset of GCA patients with intimal hyperplasia, a TAB feature associated with ischaemic sight loss.

Efficacy and safety of tocilizumab in giant cell arteritis: a single centre NHS experience using imaging (ultrasound and PET-CT) as a diagnostic and monitoring tool.

Tocilizumab (TCZ), an IL-6 receptor blocker, is approved for relapsing, refractory giant cell arteritis (GCA). We report real-life clinical experience with TCZ in GCA including assessment of responses on imaging (ultrasound (US) and 18F-Fluorodeoxyglucose Positron Emission Tomography-computed Tomography (18FDG-PET-CT)) during the first year of treatment. We included 22 consecutive patients with GCA treated with TCZ where EULAR core data set on disease activity, quality of life (QoL) and treatment-related complications were collected. Pre-TCZ US and 18FDG-PET/CT findings were available for 21 and 4 patients, respectively, where we determined the effect on US halo thickness, temporal and axillary artery Southend Halo Score and Total Vascular Score on 18FDG-PET-CT. The 22 patients with GCA (10 cranial, 10 large vessel, 2 both) had a median disease duration of 58.5 (range, 1-370) weeks prior to initiation of TCZ. Half had used prior conventional synthetic disease-modifying antirheumatic drug (csDMARDs). TCZ was initiated for refractory (50%), ischaemic (36%) or relapsing (14%) disease. Median follow-up was 43 (12-52) weeks. TCZ was discontinued due to serious adverse events (SAEs) in two patients. On treatment with TCZ, 4 discontinued prednisolone, 11 required doses ≤2.5 mg, 2 required daily dose of 2.5-5 mg and 5 needed prednisolones ≥5 mg daily. QoL improved by 50%. Total US halo thickness decreased in 38 arterial segments, median temporal artery Halo Score decreased from 11 to 0, axillary artery Halo Score remained stable. Median Total Vascular Score on FDG-PET/CT reduced from 11.5 to 6.5. In our experience, TCZ showed an excellent response with acceptable safety in GCA, with improvement on US and FDG-PET/CT imaging.

Probability-based algorithm using ultrasound and additional tests for suspected GCA in a fast-track clinic.

OBJECTIVES: Clinical presentations of giant cell arteritis (GCA) are protean, and it is vital to make a secure diagnosis and exclude mimics for urgent referrals with suspected GCA. The main objective was to develop a joined-up, end-to-end, fast-track confirmatory/exclusionary, algorithmic process based on a probability score triage to drive subsequent investigations with ultrasound (US) and any appropriate additional tests as required. METHODS: The algorithm was initiated by stratifying patients to low-risk category (LRC), intermediate-risk category (IRC) and high-risk category (HRC). Retrospective data was extracted from case records. The Southend pretest probability score (PTPS) overall showed a median score of 9 and a 75th percentile score of 12. We, therefore, classified LRC as PTPS <9, IRC 9-12 and HRC >12. GCA diagnosis was made by a combination of clinical, US, and laboratory findings. The algorithm was assessed in all referrals seen in 2018-2019 to test the diagnostic performance of US overall and in individual categories. RESULTS: Of 354 referrals, 89 had GCA with cases categorised as LRC (151), IRC (137) and HRC (66). 250 had US, whereas 104 did not (score <7, and/or high probability of alternative diagnoses). In HRC, US showed sensitivity 94%, specificity 85%, accuracy 92% and GCA prevalence 80%. In LRC, US showed sensitivity undefined (0/0), specificity 98%, accuracy 98% and GCA prevalence 0%. In IRC, US showed sensitivity 100%, specificity 97%, accuracy 98% and GCA prevalence 26%. In the total population, US showed sensitivity 97%, specificity 97% and accuracy 97%. Prevalence of GCA overall was 25%. CONCLUSIONS: The Southend PTPS successfully stratifies fast-track clinic referrals and excludes mimics. The algorithm interprets US in context, clarifies a diagnostic approach and identifies uncertainty, need for re-evaluation and alternative tests. Test performance of US is significantly enhanced with PTPS.

Halo score (temporal artery, its branches and axillary artery) as a diagnostic, prognostic and disease monitoring tool for Giant Cell Arteritis (GCA).

BACKGROUND: Giant cell arteritis (GCA) is a common large vessel vasculitis of the elderly, often associated with sight loss. Glucocorticoids (GC remain the mainstay of treatment, although biologic treatments have been approved. Biomarkers predicting disease severity, relapse rates and damage are lacking in GCA.EULAR recommends ultrasound (US) as the first investigation for suspected GCA. The cardinal US finding, a non-compressible halo, is currently categorised as either negative or positive. However, the extent and severity of this finding may vary.In this study, we hypothesise whether the extent and severity of the halo sign [calculated as a single composite Halo score (HS)] of temporal and axillary arteries may be of diagnostic, prognostic and monitoring importance; whether baseline HS is linked to disease outcomes, relapses and damage; whether HS can stratify GCA patients for individual treatment needs; whether HS can function as an objective monitoring tool during follow up. METHODS: This is a prospective, observational study. Suspected GCA Participants will be selected from the GCA FTC at the participating centres in the UK. Informed consent will be obtained, and patients managed as part of standard care. Patients with GCA will have HS (temporal and axillary arteries) measured at baseline and months 1,3,6 and 12 long with routine clinical assessments, blood sampling and patient-reported outcomes (EQ5D). Non-GCA patients will be discharged back to the referral team and will have a telephone interview in 6 months.We aim to recruit 272 suspected GCA referrals which should yield 68 patients (25% of referrals) with confirmed GCA. The recruitment will be completed in 1 year with an estimated total study period of 24 months. DISCUSSION: The identification of prognostic factors in GCA is both timely and needed. A prognostic marker, such as the HS, could help to stratify GCA patients for an appropriate treatment regimen. Tocilizumab, an IL-6R blocking agent, switches off the acute phase response (C-Reactive Protein), making it difficult to measure the disease activity. Therefore, an independent HS, and changes in that score during treatment and follow-up, maybe a more objective measure of response compare to patient-reported symptoms and clinical assessment alone.

Novel ultrasonographic Halo Score for giant cell arteritis: assessment of diagnostic accuracy and association with ocular ischaemia.

OBJECTIVES: Ultrasound of temporal and axillary arteries may reveal vessel wall inflammation in patients with giant cell arteritis (GCA). We developed a ultrasound scoring system to quantify the extent of vascular inflammation and investigated its diagnostic accuracy and association with clinical factors in GCA. METHODS: This is a prospective study including 89 patients suspected of having GCA, of whom 58 had a confirmed clinical diagnosis of GCA after 6 months follow-up. All patients underwent bilateral ultrasound examination of the three temporal artery (TA) segments and axillary arteries, prior to TA biopsy. The extent of vascular inflammation was quantified by (1) counting the number of TA segments and axillary arteries with a halo and (2) calculating a composite Halo Score that also incorporated the thickness of each halo. RESULTS: Halo counts and Halo Scores showed moderate diagnostic accuracy for a clinical diagnosis of GCA. They correlated positively with systemic inflammation. When compared with the halo count, the Halo Score correlated better with C-reactive protein (CRP) levels and allowed to firmly establish the diagnosis of GCA in more patients. Higher halo counts and Halo Scores were associated with a higher risk of ocular ischaemia. They allowed to identify subgroups of patients with low risk (≤5%) and high risk of ocular ischaemia (>30%). CONCLUSIONS: Ultrasound halo scoring allows to quantify the extent of vascular inflammation in GCA. Extensive vascular inflammation on ultrasound may provide strong diagnostic confirmation and associates with ocular ischaemia in GCA.