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A double-blind phase III trial of immunomodulating nutritional formula during adjuvant chemoradiotherapy in head and neck cancer patients: IMPATOX.
Boisselier, P, Kaminsky, MC, Thézenas, S, Gallocher, O, Lavau-Denes, S, Garcia-Ramirez, M, Alfonsi, M, Cupissol, D, de Forges, H, Janiszewski, C, et al
The American journal of clinical nutrition. 2020;(6):1523-1531
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Abstract
BACKGROUND In a previous phase II study an immunonutrient supplement was found to reduce severe acute toxicities for head and neck squamous cell cancer (HNSCC) patients treated with concomitant cisplatin and radiotherapy. OBJECTIVES The primary objective of the present study was to evaluate efficacy of the same immunonutrient supplement on severe mucositis. Secondary objectives included tolerance, compliance to oral supplementation, chemotherapy interruptions and delays, quality of life, and progression-free survival (PFS) and overall survival (OS) at 1, 2, and 3 y. METHODS Between November 2009 and June 2013, 180 HNSCC patients eligible for adjuvant chemotherapy after surgery with curative intent were included in our double-blind phase III multicenter trial. They were assigned to receive oral supplementation (3 sachets/d) of either a formula enriched with l-arginine and omega-3 (n-3) fatty and ribonucleic acids (experimental arm), or an isocaloric isonitrogenous control (control arm), for 5 d before each of 3 cycles of cisplatin. Intention-to-treat (ITT) and per-protocol (PP) analyses were undertaken, along with subgroup analyses of ≥75% compliant patients, to compare the incidence of acute mucositis (Radiation Therapy Oncology Group and WHO scales) and 36-mo survival. RESULTS At 1 mo after terminating chemoradiotherapy (CRT), no differences were observed in the incidence of grade 3-4 mucositis between treatment groups, in the ITT, PP (172 patients), and subgroup (≥75% compliance, n = 112) analyses. The immunomodulating supplement did not significantly improve survival in the ITT and PP analyses at 3 y after CRT. Among ≥75% compliant patients, however, OS at 3 y was significantly improved in the immunomodulating formula group (81%; 95% CI: 67%, 89%) compared with controls (61%; 95% CI: 46%, 73%; P = 0.034), as well as PFS (73%; 95% CI: 58%, 83% compared with 50%; 95% CI: 36%, 63%; P = 0.012). CONCLUSIONS Although this immunomodulating formula failed to reduce severe mucositis during CRT, the findings suggest that the long-term survival of compliant HNSCC patients was improved.This trial was registered at clinicaltrials.gov as NCT01149642.
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Treatments for inverse psoriasis: a systematic review.
Reynolds, KA, Pithadia, DJ, Lee, EB, Wu, JJ
The Journal of dermatological treatment. 2020;(8):786-793
Abstract
Background: Inverse psoriasis often requires a targeted treatment strategy due to the inherent sensitivity, thinness, and occlusion of flexural areas. However, most treatment recommendations are based on anecdotal evidence.Methods: A systematic literature search was conducted in October 2018 in Pubmed, Scopus, Embase, and Cochrane Library with keywords 'inverse psoriasis,' 'genital psoriasis,' and 'treatment.' All prospective studies assessing efficacy of treatments for inverse psoriasis that had a sample size of at least 10 patients were included in our analysis.Results: The initial search yielded 340 results, and 14 studies were included in the final analysis. These studies comprised over 1000 patients with mild to severe psoriasis involving axillary, inframammary, facial, and/or anogenital regions. The included studies demonstrated efficacy of topical immunomodulators (N = 7), vitamin D analogs (N = 4), topical corticosteroids (N = 3), antiseptics (N = 2), and biologics (N = 1) in improving genital and flexural psoriasis symptoms.Conclusions: There is a paucity of high-quality studies on which to base treatment recommendations, especially with regard to the role of systemic and biologic therapies. Few studies, many of which are of low evidence quality, suggest that topical immunomodulators, vitamin D analogs, and mid-to-high-potency topical corticosteroids may be effective treatments, but more randomized controlled trials are needed.
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Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti-TNF or conventional therapy: results of the European CONCEIVE study.
Moens, A, van der Woude, CJ, Julsgaard, M, Humblet, E, Sheridan, J, Baumgart, DC, Gilletta De Saint-Joseph, C, Nancey, S, Rahier, JF, Bossuyt, P, et al
Alimentary pharmacology & therapeutics. 2020;(1):129-138
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Abstract
BACKGROUND Women with inflammatory bowel diseases (IBD) often receive biologicals during pregnancy to maintain disease remission. Data on outcome of vedolizumab-exposed pregnancies (VDZE) are sparse. AIMS To assess pregnancy and child outcomes of VDZE pregnancies and to compare these results to anti-TNF exposed (TNFE) or both immunomodulatory and biologic unexposed (CON IBD) pregnancies. METHODS A retrospective multicentre case-control observational study was performed. RESULTS VDZE group included 79 pregnancies in 73 IBD women. The TNFE and CON IBD group included 186 pregnancies (162 live births) in 164 IBD women and 184 pregnancies (163 live births) in 155 IBD women, respectively. At conception, cases more often had active disease ([VDZE: 36% vs TNFE 17%, P = .002] and [VDZE: 36% vs CON IBD 24%, P = .063]). No significant difference in miscarriage rates were found between groups (VDZE and TNFE 16% vs 13%, P = .567; VDZE and CON IBD 16% vs 10%, P = .216). In live-born infants, median gestational age and birthweight were similar between groups. Median Apgar score at birth was numerically equal. Prematurity was similar in the VDZE group compared to the control groups, even when correcting for disease activity during pregnancy. The frequency of congenital anomalies was comparable between groups as were the percentages of breastfed babies. During the first year of life, no malignancies were reported and infants' infection risk did not significantly differ between groups. CONCLUSION No new safety signal was detected in VDZE pregnancies although larger, prospective studies are required for confirmation.
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Vitamin D Effects on the Immune System from Periconception through Pregnancy.
Schröder-Heurich, B, Springer, CJP, von Versen-Höynck, F
Nutrients. 2020;(5)
Abstract
Vitamin D is a well-known secosteroid and guardian of bone health and calcium homeostasis. Studies on its role in immunomodulatory functions have expanded its field in recent years. In addition to its impact on human physiology, vitamin D influences the differentiation and proliferation of immune system modulators, interleukin expression and antimicrobial responses. Furthermore, it has been shown that vitamin D is synthesized in female reproductive tissues and, by modulating the immune system, affects the periconception period and reproductive outcomes. B cells, T cells, macrophages and dendritic cells can all synthesize active vitamin D and are involved in processes which occur from fertilization, implantation and maintenance of pregnancy. Components of vitamin D synthesis are expressed in the ovary, decidua, endometrium and placenta. An inadequate vitamin D level has been associated with recurrent implantation failure and pregnancy loss and is associated with pregnancy-related disorders like preeclampsia. This paper reviews the most important data on immunomodulatory vitamin D effects in relation to the immune system from periconception to pregnancy and provides an insight into the possible consequences of vitamin D deficiency before and during pregnancy.
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Transfer of monoclonal antibodies into breastmilk in neurologic and non-neurologic diseases.
LaHue, SC, Anderson, A, Krysko, KM, Rutatangwa, A, Dorsey, MJ, Hale, T, Mahadevan, U, Rogers, EE, Rosenstein, MG, Bove, R
Neurology(R) neuroimmunology & neuroinflammation. 2020;(4)
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Abstract
OBJECTIVE To review currently available data on the transfer of monoclonal antibodies (mAbs) in the breastmilk of women receiving treatment for neurologic and non-neurologic diseases. METHODS We systematically searched the medical literature for studies referring to 19 selected mAb therapies frequently used in neurologic conditions and "breastmilk," "breast milk," "breastfeeding," or "lactation." From an initial list of 288 unique references, 29 distinct full-text studies met the eligibility criteria. One additional study was added after the literature search based on expert knowledge of an additional article. These 30 studies were reviewed. These assessed the presence of our selected mAbs in human breastmilk in samples collected from a total of 155 individual women. RESULTS Drug concentrations were typically low in breastmilk and tended to peak within 48 hours, although maximum levels could occur up to 14 days from infusion. Most studies did not evaluate the breastmilk to maternal serum drug concentration ratio, but in those evaluating this, the highest ratio was 1:20 for infliximab. Relative infant dose, a metric comparing the infant with maternal drug dose (<10% is generally considered safe), was evaluated for certolizumab (<1%), rituximab (<1%), and natalizumab (maximum of 5.3%; cumulative effects of monthly dosing are anticipated). Importantly, a total of 368 infants were followed for ≥6 months after exposure to breastmilk of mothers treated with mAbs; none experienced reported developmental delay or serious infections. CONCLUSIONS The current data are reassuring for low mAb drug transfer to breastmilk, but further studies are needed, including of longer-term effects on infant immunity and childhood development.
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Exploring the Evidence for an Immunomodulatory Role of Vitamin D in Juvenile and Adult Rheumatic Disease.
Zou, J, Thornton, C, Chambers, ES, Rosser, EC, Ciurtin, C
Frontiers in immunology. 2020;:616483
Abstract
Vitamin D is synthesized in the skin following exposure to UVB radiation or is directly absorbed from the diet. Following hydroxylation in the liver and kidneys, vitamin D becomes its bioactive form, 1,25(OH)2D, which has been described to have potent immunomodulatory capacity. This review will focus on the effect of vitamin D in modulating the dysregulated immune system of autoimmune rheumatic diseases (ARD) patients across age, in particular in arthritis (rheumatoid arthritis and juvenile idiopathic arthritis), and systemic lupus erythematosus (with adult and juvenile onset). As well as delineating the impact of vitamin D on the innate and adaptive immune functions associated with each disease pathology, this review will also summarize and evaluate studies that link vitamin D status with disease prevalence, and supplementation studies that examine the potential benefits of vitamin D on disease outcomes. Exploring this evidence reveals that better designed randomized controlled studies are required to clarify the impact of vitamin D supplementation on ARD outcomes and general health. Considering the accessibility and affordability of vitamin D as a therapeutic option, there is a major unmet need for evidence-based treatment recommendations for the use of vitamin D in this patient population.
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An Overview of Ozone Therapy for Treating Foot Ulcers in Patients With Diabetes.
Wen, Q, Chen, Q
The American journal of the medical sciences. 2020;(2):112-119
Abstract
Diabetic foot ulcer (DFU) is one of the most common and severe complications of diabetes mellitus, which is becoming increasingly prevalent throughout the world, with high mortality and morbidity. Because of the complex pathophysiological processes involved, DFU is difficult to treat effectively with traditional therapies. Ozone therapy, an emerging method, has been reported as potentially beneficial for closure of DFUs and may gradually move to the forefront of clinical practice. Possible mechanisms of action include antioxidant capacity, pathogen inactivation, vascular and endogenous growth factor modulation, and immune system activation. However, some researchers are skeptical about its safety, and clinical trials are lacking. This article reviews the current research and application of ozone therapy for DFUs.
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Lactoferrin as potential preventative and adjunct treatment for COVID-19.
Chang, R, Ng, TB, Sun, WZ
International journal of antimicrobial agents. 2020;(3):106118
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The coronavirus disease 2019 (COVID-19) pandemic is rapidly advancing across the globe despite drastic public and personal health measures. Antivirals and nutritional supplements have been proposed as potentially useful against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that causes COVID-19, but few have been clinically established. Lactoferrin (Lf) is a naturally occurring, non-toxic glycoprotein that is orally available as a nutritional supplement and has established in vitro antiviral efficacy against a wide range of viruses, including SARS-CoV, a closely related coronavirus to SARS-CoV-2. Furthermore, Lf possesses unique immunomodulatory and anti-inflammatory effects that may be especially relevant to the pathophysiology of severe COVID-19 cases. Here we review the underlying biological mechanisms of Lf as an antiviral and immune regulator, and propose its unique potential as a preventative and adjunct treatment for COVID-19. We hope that further research and development of Lf nutritional supplementation would establish its role for COVID-19.
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Approach to patients with hypophosphataemia.
Florenzano, P, Cipriani, C, Roszko, KL, Fukumoto, S, Collins, MT, Minisola, S, Pepe, J
The lancet. Diabetes & endocrinology. 2020;(2):163-174
Abstract
Phosphate metabolism is an evolving area of basic and clinical research. In the past 15 years, knowledge on disturbances of phosphate homoeostasis has expanded, as has the discovery of new targeted therapies. Hypophosphataemia might be the biochemical finding in several diseases, and its clinical evaluation should initially focus on the assessment of pathophysiological mechanisms leading to low serum phosphate concentrations. Clinical consequences of hypophosphataemia can involve multiple organ systems and vary depending on several factors, the most important being the underlying disorder. This Review focuses on the approach to patients with hypophosphataemia and how underlying pathophysiological mechanisms should be understood in the evaluation of differential diagnosis. We define an algorithm for the assessment of hypophosphataemia and review the most up-to-date literature on specific therapies. Continuous research in this area will result in a better understanding and management of patients with hypophosphataemia.
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Combination Therapy of Adalimumab With an Immunomodulator Is Not More Effective Than Adalimumab Monotherapy in Children With Crohn's Disease: A Post Hoc Analysis of the PAILOT Randomized Controlled Trial.
Matar, M, Shamir, R, Turner, D, Broide, E, Weiss, B, Ledder, O, Guz-Mark, A, Rinawi, F, Cohen, S, Topf-Olivestone, C, et al
Inflammatory bowel diseases. 2020;(11):1627-1635
Abstract
BACKGROUND The PAILOT trial was a randomized controlled trial aimed to evaluate proactive vs reactive therapeutic drug monitoring in children with Crohn's disease (CD) treated with adalimumab. Our aim in this post hoc analysis of the PAILOT trial was to assess the efficacy and safety of adalimumab combination treatment in comparison with monotherapy at week 72 after adalimumab induction. METHODS Participants were children 6-17 years old, biologic naïve, with moderate to severe CD, who responded to adalimumab induction at week 4. Patients receiving immunomodulators at baseline maintained a stable dose until week 24; patients could then discontinue immunomodulators. At each visit, patients were assessed for disease index, serum biomarkers, fecal calprotectin, adalimumab trough concentration, and anti-adalimumab antibodies. RESULTS Out of the 78 patients (29% female; mean age, 14.3 ± 2.6 years), 34 patients (44%) received combination therapy. During the study period, there was no significant difference in the rates of sustained corticosteroid-free clinical remission (25/34, 73%, vs 28/44, 63%; P = 0.35) or sustained composite outcome of clinical remission, C-reactive protein ≤0.5 mg/dL, and calprotectin ≤150 µg/g (10/34, 29%, vs 14/44, 32%; P = 0.77) between the combination group and the monotherapy group, respectively. Clinical and biological outcomes did not differ between the proactive and reactive subgroups within the combination and monotherapy groups. Adalimumab trough concentrations and immunogenicity were not significantly different between groups. The rate of serious adverse events was not significantly different between groups but was numerically higher in the monotherapy group. CONCLUSIONS Combination therapy of adalimumab and an immunomodulator was not more effective than adalimumab monotherapy in children with CD (ClinicalTrials.gov No. NCT02256462).