scholarly journals X-Linked Hypophosphatemia: A New Era in Management

2020 ◽  
Vol 4 (12) ◽  
Author(s):  
Kathryn Dahir ◽  
Mary Scott Roberts ◽  
Stan Krolczyk ◽  
Jill H Simmons
Keyword(s):  
Fibroblast Growth Factor 23 ◽  
Treatment Options ◽  
Human Monoclonal Antibody ◽  
Loss Of Function ◽  
Active Vitamin ◽  
New Era ◽  
Dihydroxyvitamin D ◽  
Conventional Management ◽  
Phex Gene

Abstract X-linked hypophosphatemia (XLH) is a rare, hereditary, progressive musculoskeletal disease that often causes pain and short stature, as well as decreased physical function, mobility, and quality of life. Hypophosphatemia in XLH is caused by loss of function mutations in the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene, resulting in excess levels of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23), which leads to renal phosphate wasting and decreased serum 1,25-dihydroxyvitamin D production. Historically, treatment options were limited to oral phosphate and active vitamin D analogues (conventional management) dosed several times daily in an attempt to improve skeletal mineralization by increasing serum phosphorus. The recent approval of burosumab, a fully human monoclonal antibody to FGF23, has provided a new, targeted treatment option for patients with XLH. This review summarizes our current understanding of XLH, the safety and efficacy of conventional management and burosumab, existing recommendations for managing patients, and unanswered questions in the field.

scholarly journals 635 Expectations and Concerns of Patients Attending a Spinal Outpatient Clinic

2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
T Jones ◽  
A Stanley ◽  
M J H McCarthy
Keyword(s):  
Outpatient Clinic ◽  
Treatment Options ◽  
Healthcare Systems ◽  
Loss Of Function ◽  
Previous Surgery ◽  
Permanent Disability ◽  
Work Related ◽  
Clinical Consultation ◽  
Future Work

Abstract Aim Identifying expectations and concerns of patients is vital during clinical consultation in patient-centred healthcare systems. Most spinal surgery is elective and focussed on improving quality of life. Understanding what patients want from treatment at baseline may improve experience and outcomes. Method New patient data from the caseload of a single orthopaedic spinal surgeon (from April 2012-18) was analysed with expectations and concerns reported in the outpatient clinic letter (standard practice for surgeon). Results Of 940 patients (498 NHS, 442 private), mean age was 58.3 with 46.0% male and 54.0% female. Nearly 1-in-6 patients underwent previous surgery. The most common expectation was ‘reduce pain’ (41.8%), followed by diagnosis (23.0%), treatment options (13.5%), unsure (10.5%). The most common concern was ‘continuation/worsening of pain’ (27.0%), followed by loss of function (15.9%), work-related (8.3%), permanent disability (7.8%). NHS patients were significantly more unsure of expectations (19.7% vs 4.5%, p<.001) and less frequently raised concerns (39.0% vs 18.8%, p<.001). NHS patients had significantly worse Oswestry Disability Index (ODI) scores (46.8% vs 42.0% p<.001), were more depressed (PHQ-9: 11.5 vs 8.9, p<.001) and anxious (GAD-7: 8.2 vs 5.9, p<.001). Private patients were significantly more likely to report problems sleeping (79.4% vs 51.0%, p<.001). Patients concerned about permanent disability had significantly worse ODI (51.0% vs 42.7%, p<.001), PHQ-9 (12.6 vs 10.2 p=.013) and GAD-7 (9.0 vs 7.1, p=.017) scores. Conclusions This study identified patient expectations and concerns in spinal outpatient clinic in both healthcare sectors. Future work should explore these findings in context with clinical outcome.

scholarly journals Systemic treatment of psoriasis: from methotrexate to biologics

2020 ◽  
Vol 96 (3) ◽  
pp. 7-26
Author(s):  
Olga Yu. Olisova ◽  
Ekaterina M. Anpilogova
Keyword(s):  
Skin Diseases ◽  
Systemic Treatment ◽  
Treatment Options ◽  
Certolizumab Pegol ◽  
Severe Psoriasis ◽  
Unknown Etiology ◽  
Inflammatory Skin Diseases ◽  
New Era ◽  
Complete Clinical Remission

Psoriasis is one of the most frequent chronic inflammatory skin diseases and it has been of interest to many scientists for ages. The review presents data on all systemic treatment options, that are to date officially registered in Russian Federation for moderate-to-severe psoriasis. Aspects of the mechanism of action, efficacy and tolerability of both basic drugs (methotrexate, cyclosporine, acitretin) and biologics (infliximab, adalimumab, etanercept, certolizumab pegol, ustekinumab, guselkumab, secukinumab, ixekizumab, netakimab) and small molecules (tofacitinib, apremilast) are considered in detail. Special emphasis is placed on the important nuances of biological therapy: immunogenicity, drugs' survival and switch due to lack of efficacy. Invention of biologics signified a new era of moderate-to-severe psoriasis treatment. It became possible to achieve complete clinical remission more safely, which significantly improved the quality of life of patients. However, due to the unknown etiology of psoriasis, there is still no universal remedy that would allow to cure every patient, this fact makes scientists from all over the world keep conducting numerous clinical trials to find even more effective and safe therapeutic options.

scholarly journals A Case Report of Compound Heterozygous CYP24A1 Mutations Leading to Nephrolithiasis Successfully Treated with Ketoconazole

2017 ◽  
Vol 7 (3) ◽  
pp. 167-171 ◽  
Author(s):  
Emma Davidson Peiris ◽  
Raghav Wusirika
Keyword(s):  
Vitamin D ◽  
Treatment Options ◽  
Elevated Serum ◽  
Compound Heterozygous ◽  
Loss Of Function ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Idiopathic Infantile Hypercalcemia

CYP24A1 is an enzyme that inactivates vitamin D. Loss-of-function mutations in this enzyme are rare but have been linked with idiopathic infantile hypercalcemia as well as adult-onset nephrocalcinosis and nephrolithiasis. Genetic testing for this mutation should be considered in the presence of calciuria, elevated serum calcium, elevated 1,25-dihydroxyvitamin D, and suppressed parathyroid hormone. We present a case with these lab findings as well as an elevated 25-hydroxyvitamin D/24,25-dihydroxyvitamin D ratio in whom compound heterozygous CYP24A1 mutations were found. His hypercalciuria resolved and 1,25-vitamin D level improved with ketoconazole treatment. We suggest that it is clinically important to identify patients with this phenotype as testing and treatment options are available which could reduce progression to chronic kidney disease in this population.

Rachitismo ipofosforemico X-linked

2020 ◽  
Vol 39 (7) ◽  
pp. 430-436
Author(s):  
Laura Lucchetti ◽  
Francesco Emma ◽  
Danilo Fintini ◽  
Marco Cappa
Keyword(s):  
Clinical Symptoms ◽  
Fibroblast Growth Factor 23 ◽  
Vitamin D Supplementation ◽  
Elevated Alkaline Phosphatase ◽  
Dihydroxyvitamin D ◽  
Igg1 Monoclonal Antibody ◽  
Physical Dysfunction ◽  
Phex Gene ◽  
Fgf 23 ◽  
Phosphate Salts

X-linked hypophosphatemia (XLH) is an X-linked disorder with dominant penetration, caused by mutations in the PHEX gene, which encodes for an endopeptidase that is predominantly expressed in osteoblasts, osteocytes and odontoblasts. PHEX mutations cause increased production of fibroblast growth factor 23 (FGF23) that in turn leads to hypophosphatemia by causing inhibition of the renal phosphate reabsorption and of the synthesis of active 1,25-dihydroxyvitamin D. In children XLH is characterised by rickets, bone pain, physical dysfunction, impaired growth, disproportionate short stature, lowerlimb deformities, pathological fractures, dental malposition and dental abscesses. Although phenotype may be variable in severity, early diagnosis and treatment are critical to improve outcome. Laboratory tests show hypophosphatemia associated with hyperphosphaturia and elevated alkaline phosphatase, while parathormone and calcium levels are normal. For decades, patients have been treated with conventional therapy, including active vitamin D supplementation and fractionated daily doses of oral phosphate salts. However, these therapies rarely normalise the phenotype. More recently, burosumab, a recombinant human IgG1 monoclonal antibody against FGF-23, has been introduced for the treatment of XLH. In phase 2 trials, burosumab has been shown to improve significantly clinical symptoms, as well as biological and radiological signs of rickets.

scholarly journals Ap2s1 mutation in mice causes familial hypocalciuric hypercalcemia type 3

2020 ◽  
Author(s):  
Fadil M. Hannan ◽  
Mark Stevenson ◽  
Asha L. Bayliss ◽  
Victoria J. Stokes ◽  
Michelle Stewart ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Fibroblast Growth Factor 23 ◽  
Plasma Concentrations ◽  
Adaptor Protein ◽  
Endosomal Trafficking ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Loss Of Function ◽  
Dihydroxyvitamin D ◽  
Sigma Subunit ◽  
Type 3

AbstractMutations of the adaptor protein-2 sigma subunit (AP2S1) gene which encodes AP2σ2, a component of the ubiquitous AP2 heterotetrameric complex involved in endosomal trafficking of the calcium-sensing receptor (CaSR), cause familial hypocalciuric hypercalcemia type 3 (FHH3). FHH3 patients have heterozygous AP2S1 missense Arg15 mutations (p.Arg15Cys, p.Arg15His or p.Arg15Leu) with marked hypercalcemia and occasional hypophosphatemia and osteomalacia. To further characterise the phenotypic spectrum and calcitropic pathophysiology of FHH3, we used CRISPR/Cas9 genome editing to generate mice harboring the AP2S1 p.Arg15Leu mutation, which causes the most severe FHH3 phenotype. Heterozygous (Ap2s1+/L15) mice were viable, and had marked hypercalcemia, hypermagnesemia, hypophosphatemia, and increased plasma concentrations of parathyroid hormone, fibroblast growth factor 23 and alkaline phosphatase activity, but normal pro-collagen type 1 N-terminal pro-peptide and 1,25 dihydroxyvitamin D. Homozygous (Ap2s1L15/L15) mice invariably died perinatally. The AP2S1 p.Arg15Leu mutation impaired protein-protein interactions between AP2σ2 and the other AP2 subunits, and the CaSR. Cinacalcet, a CaSR allosteric activator, ameliorated the hypercalcemia and elevated PTH concentrations, but not the diminished AP2σ2-CaSR interaction. Thus, our studies have established a mouse model with a germline loss-of-function AP2S1 mutation that is representative for FHH3 in humans, and demonstrated that cinacalcet corrects the abnormalities of plasma calcium and PTH.

Surgery for Lung Cancer and the Consequences for the Swallow

2016 ◽  
Vol 1 (13) ◽  
pp. 162-168
Author(s):  
Pippa Hales ◽  
Corinne Mossey-Gaston
Keyword(s):  
Lung Cancer ◽  
Treatment Options ◽  
Vocal Cord Palsy ◽  
Subsequent Treatment ◽  
Physiological Reserve ◽  
Palliative Phase ◽  
And Function ◽  
The Impact ◽  
Swallow Function

Lung cancer is one of the most commonly diagnosed cancers across Northern America and Europe. Treatment options offered are dependent on the type of cancer, the location of the tumor, the staging, and the overall health of the person. When surgery for lung cancer is offered, difficulty swallowing is a potential complication that can have several influencing factors. Surgical interaction with the recurrent laryngeal nerve (RLN) can lead to unilateral vocal cord palsy, altering swallow function and safety. Understanding whether the RLN has been preserved, damaged, or sacrificed is integral to understanding the effect on the swallow and the subsequent treatment options available. There is also the risk of post-surgical reduction of physiological reserve, which can reduce the strength and function of the swallow in addition to any surgery specific complications. As lung cancer has a limited prognosis, the clinician must also factor in the palliative phase, as this can further increase the burden of an already compromised swallow. By understanding the surgery and the implications this may have for the swallow, there is the potential to reduce the impact of post-surgical complications and so improve quality of life (QOL) for people with lung cancer.

Letter to the Editor: The Continuing Challenge of Evaluating RSD Impairment and Disability

1998 ◽  
Vol 3 (5) ◽  
pp. 8-10
Author(s):  
Robert L. Knobler ◽  
Charles N. Brooks ◽  
Leon H. Ensalada ◽  
James B. Talmage ◽  
Christopher R. Brigham
Keyword(s):  
Disability Evaluation ◽  
Body Part ◽  
Loss Of Function ◽  
Regulatory Requirements ◽  
Major Cardiac Event ◽  
Clinical Scenarios ◽  
Impairment Score ◽  
Occupational Activities ◽  
The Difference

Abstract The author of the two-part article about evaluating reflex sympathetic dystrophy (RSD) responds to criticisms that a percentage impairment score may not adequately reflect the disability of an individual with RSD. The author highlights the importance of recognizing the difference between impairment and disability in the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides): impairment is the loss, loss of use, or derangement of any body part, system, or function; disability is a decrease in or the loss or absence of the capacity to meet personal, social, or occupational demands or to meet statutory or regulatory requirements because of an impairment. The disparity between impairment and disability can be encountered in diverse clinical scenarios. For example, a person's ability to resume occupational activities following a major cardiac event depends on medical, social, and psychological factors, but nonmedical factors appear to present the greatest impediment and many persons do not resume work despite significant improvements in functional capacity. A key requirement according to the AMA Guides is objective documentation, and the author agrees that when physicians consider the disability evaluation of people, more issues than those relating to the percentage loss of function should be considered. More study of the relationships among impairment, disability, and quality of life in patients with RSD are required.

Raynaud’s phenomenon and digital ischaemia - pharmacologic approach and alternative treatment options

VASA ◽  
2016 ◽  
Vol 45 (3) ◽  
pp. 201-212 ◽  
Author(s):  
Birgit Linnemann ◽  
Matthias Erbe
Keyword(s):  
Quality Of Life ◽  
Angiotensin Receptor Blockers ◽  
Raynaud’S Phenomenon ◽  
Treatment Options ◽  
Raynaud's Phenomenon ◽  
Tissue Loss ◽  
Receptor Antagonists ◽  
Skin Ulcers ◽  
Digital Ischaemia

Abstract. The primary goal of therapy is to reduce the frequency and intensity of Raynaud’s attacks and to minimize the related morbidity rather than to cure the underlying condition. Treatment strategies depend on whether Raynaud’s phenomenon (RP) is primary or secondary. All patients should be instructed about general measures to maintain body warmth and to avoid triggers of RP attacks. Pharmacologic intervention can be useful for patients with severe and frequent RP episodes that impair the patient’s quality of life. Calcium channel blockers are currently the most prescribed and studied medications for this purpose. There has been limited evidence for the efficacy of alpha-1-adrenergic receptor antagonists, angiotensin receptor blockers, topical nitrates or fluoxetine to treat RP. The intravenously administered prostacyclin analogue iloprost can reduce the frequency and severity of RP attacks and is considered a second-line therapy in patients with markedly impaired quality of life, critical digital ischaemia and skin ulcers who are at risk for substantial tissue loss and amputation. Phosphodiesterase inhibitors (e.g., sildenafil) can also improve RP symptoms and ulcer healing whereas endothelin-1 receptor antagonists (e.g., bosentan) are mainly considered treatment options in secondary prevention for patients with digital skin ulcers related to systemic sclerosis. However, their use in clinical practice has been limited by their high cost. Antiplatelet therapy with low-dose aspirin is recommended for all patients who suffer from secondary RP due to ischaemia caused by structural vessel damage. Anticoagulant therapy can be considered during the acute phase of digital ischaemia in patients with suspected vascular occlusive disease attributed to the occurrence of new thromboses. In patients with critical digital ischaemia, consideration should be given to hospitalisation, optimisation of medical treatment in accordance with the underlying disease and evaluation for a secondary, possibly reversible process that is causing or aggravating the clinical symptoms.

Chronic Ischemic Monomelic Neuropathy after Arteriovenous Fistula Creation: A Unique Presentation of Vascular Steal

2020 ◽  
Vol 3 (2) ◽  
pp. 147-150
Author(s):  
Kaczynski RE ◽  
Asaad Y ◽  
Valentin-Capeles N ◽  
Battista J
Keyword(s):  
Arteriovenous Fistula ◽  
Complete Loss ◽  
Dialysis Access ◽  
Loss Of Function ◽  
Access Site ◽  
Surgical Ligation ◽  
Arteriovenous Access ◽  
Vascular Steal ◽  
Steal Syndrome

We discuss a case of a 58 year old male who presented for left upper extremity steal syndrome including ischemic monomelic neuropathy (IMN) 1.5 months after arteriovenous fistula creation. He presented after three surgical attempts to salvage his fistula with rest pain, complete loss of function with contracture of the 4th and 5th digits, and loss of sensation in the ulnar distribution for more than three weeks. At our institution, he underwent surgical ligation of the distal fistula and creation of a new fistula proximally, resulting in complete resolution of his vascular steal symptoms almost immediately despite the chronicity prior to surgical presentation. Our patient provides a unique perspective regarding dialysis access salvage versus patient quality of life. The patients’ functional status and pain levels should take precedence over salvage of an arteriovenous access site, and early ligation of the access should be completed prior to chronic IMN development. However, if a patient presents late along the IMN course, we recommend strong consideration of access ligation in order to attempt to regain the full neurovascular function of the extremity as we experienced in our patient.

Vitamin C as an Anticancer Agent: Regulation of Signaling Pathways

2020 ◽  
Vol 20 (21) ◽  
pp. 1868-1875
Author(s):  
Ghazala Butt ◽  
Ammad A. Farooqi ◽  
Aima Adylova ◽  
Rukset Attar ◽  
Seher Yilmaz ◽  
...  
Keyword(s):  
Vitamin C ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Scientific Evidence ◽  
Treatment Options ◽  
Published Data ◽  
New Era ◽  
Molecular Oncology ◽  
Anticancer Effects ◽  
Oncogenic Pathways

Treatment options for effective treatment of cancer with minimum off-target effects and maximum clinical outcomes have remained overarching goals in the clinical oncology. Vitamin C has remained in the shadows of controversy since the past few decades; burgeoning evidence has started to shed light on wide-ranging anticancer effects exerted by Vitamin C to induce apoptosis in drug-resistant cancer cells, inhibit uncontrolled proliferation of the cancer cells and metastatic spread. Landmark achievements in molecular oncology have ushered in a new era, and researchers have focused on the identification of oncogenic pathways regulated by Vitamin C in different cancers. However, there are visible knowledge gaps in our understanding related to the ability of Vitamin C to modulate a myriad of transduction cascades. There are scattered pieces of scientific evidence about promising potential of Vitamin C to regulate JAK-STAT, TGF/SMAD, TRAIL and microRNAs in different cancers. However, published data is insufficient and needs to be investigated comprehensively to enable basic and clinical researchers to reap full benefits and promote result-oriented transition of Vitamin C into various phases of clinical trials. In this review, we will emphasize on available evidence related to the regulation of oncogenic cell signaling pathways by Vitamin C in different cancers. We will also highlight the conceptual gaps, which need detailed and cutting-edge research.

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