scholarly journals Glucocorticoids in Graves’ orbitopathy: mechanisms of action and clinical application

2020 ◽  
Vol 11 ◽  
pp. 204201882095833
Author(s):  
Jan Längericht ◽  
Irene Krämer ◽  
George J. Kahaly
Keyword(s):  
Low Cost ◽  
Standard Of Care ◽  
Daily Basis ◽  
Clinical Severity ◽  
Line Treatment ◽  
First Line ◽  
Graves Orbitopathy ◽  
Meta Analyses ◽  
First Line Treatment

Background: Graves’ orbitopathy (GO) is the most frequent extrathyroidal manifestation of the autoimmune Graves’ disease. GO significantly impacts quality of life and has a psycho-social morbidity. Inflammation and swelling of the orbital tissue often leads to proptosis, diplopia, and decrease of visual acuity. Due to the inflammatory background of the disease, glucocorticoids (GC) have been used as a first-line treatment for decades. Methods: PubMed and MeSH database were searched for original articles, clinical trials, reviews, and meta-analyses published between 1 January 2000 and 31 March 2020 and pertaining to both the mechanism of action and immunological effects of GC as well as to the treatment of GO by GC. The publications were evaluated according to their setting and study design. Results: GC act through genomic (trans-activation and trans-repression) and rapid non-genomic mechanisms. GC in general, and the intravenous (IV) administration of GC in particular, markedly decrease the activity and number of the most potent antigen-presenting dendritic cells. According to the internationally acknowledged European Thyroid Association Guidelines for the management of GO, weekly IVGC application over 12 weeks is recommended as first-line treatment for patients with active and severe GO. The daily and cumulative dose should be tailored according to clinical severity, for example, 4.5 g of IV methylprednisolone for the inflammatory component versus 7.5 g in the presence of diplopia and severe proptosis. Fast and significant improvements in orbital symptoms and signs are noted in 65–70% of patients. Long-term experience over decades, and worldwide availability at low cost, underline the clinical and therapeutic relevance of GC. Adverse events are rarely severe, dose-dependent, and usually reversible, hence easy to handle by medical investigators. Oral GC application on a daily basis is characterized by high bioavailability but reduced efficacy and increased toxicity. Conclusion: IVGC still represents the standard of care in active/severe GO. Innovative biologicals, like monoclonal antibodies targeting the thyrotropin/Insulin-like growth factor-1 receptors or pro-inflammatory cytokines (e.g., Interleukin-6) should be compared with standard GC treatment with respect to short- and long-term efficacy, safety, costs, and global availability.

scholarly journals First line treatment selection modifies disease course and long-term clinical outcomes in Mycobacterium avium complex pulmonary disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kiyoharu Fukushima ◽  
Seigo Kitada ◽  
Sho Komukai ◽  
Tomoki Kuge ◽  
Takanori Matsuki ◽  
...  
Keyword(s):  
Pulmonary Disease ◽  
Mycobacterium Avium ◽  
Propensity Scores ◽  
Cox Regression ◽  
Line Treatment ◽  
First Line ◽  
Standard Regimen ◽  
Cox Regression Analysis ◽  
First Line Treatment

AbstractThe combination of rifamycin (RFP), ethambutol (EB), and macrolides is currently the standard regimen for treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). However, poor adherence to the standardized regimens recommended by current guidelines have been reported. We undertook a single-centred retrospective cohort study to evaluate the long-term outcomes in 295 patients with MAC-PD following first line treatment with standard (RFP, EB, clarithromycin [CAM]) or alternative (EB and CAM with or without fluoroquinolones (FQs) or RFP, CAM, and FQs) regimens. In this cohort, 80.7% were treated with standard regimens and 19.3% were treated with alternative regimens. After heterogeneity was statistically corrected using propensity scores, outcomes were superior in patients treated with standard regimens. Furthermore, alternative regimens were significantly and independently associated with sputum non-conversion, treatment failure and emergence of CAM resistance. Multivariate cox regression analysis revealed that older age, male, old tuberculosis, diabetes mellitus, higher C-reactive protein, and cavity were positively associated with mortality, while higher body mass index and M. avium infection were negatively associated with mortality. These data suggest that, although different combination regimens are not associated with mortality, first line administration of a standard RFP + EB + macrolide regimen offers the best chance of preventing disease progression in MAC-PD patients.

Topical Timolol for Infantile Haemangioma of the Orbit

2021 ◽  
Vol 238 (10) ◽  
pp. 1069-1076
Author(s):  
Göran Darius Hildebrand ◽  
Zuzana Sipkova
Keyword(s):  
Adverse Effects ◽  
Beta Blockers ◽  
Close Monitoring ◽  
Line Treatment ◽  
Timolol Maleate ◽  
First Line ◽  
Benign Tumours ◽  
Meta Analyses ◽  
Oral Propranolol ◽  
First Line Treatment

AbstractInfantile haemangiomas (IHs) are the most common benign tumours of the eyelid and orbits in infancy. Beta-blockers, in the form of oral propranolol, have become first-line treatment in severe cases with functionally significant or disfiguring IH. However, adverse drug reactions of oral propranolol in infants are reported in 1 in 11 and serious or potentially life-threatening systemic side effects in 1 in 38, including dyspnoea, hypotension, hyperkalaemia, hypoglycaemia, and cyanosis, therefore requiring careful and close monitoring during the course of systemic treatment. More recently, two large meta-analyses have shown topical beta-blockers, such as timolol maleate 0.5%, to be as effective as oral propranolol in superficial IH, but with no or significantly fewer adverse effects, and have advocated that topical beta-blockers replace oral propranolol as the first-line treatment of superficial IH. We have previously reported the therapeutic response of deep periocular IH to primary topical timolol maleate 0.5% monotherapy. Here we also describe the first successful treatments of large orbital IHs with primary topical timolol maleate 0.5% monotherapy in four infants, resulting in immediate cessation of progression and rapid clinical improvement or resolution in all cases. No adverse effects and no recurrence during long-term follow-up of up to 2.5 years after cessation were seen in any of the patients treated with topical timolol maleate 0.5%.

scholarly journals Clinical and Biological Characteristics and Outcomes of Richter Transformation : A French Multicenter Study from the Filo Group

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4112-4112
Author(s):  
Charline Moulin ◽  
Romain Morizot ◽  
Thomas Remen ◽  
Hélène Augé ◽  
Florian Bouclet ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Intermediate Risk ◽  
Line Treatment ◽  
First Line ◽  
Advisory Committees ◽  
Long Term Survivors ◽  
First Line Treatment

Introduction: About 2 to 10% of patients (pts) diagnosed with Chronic Lymphocytic Leukemia (CLL) develop diffuse large B-cell lymphoma (DLBCL, so-called Richter transformation (RT)) over long-term follow-up. The outcomes of pts with RT are variable and poorly understood and there is no consensus on the best therapeutic approach. The aim of this study was to analyze the clinical characteristics, outcomes and factors predictive of survival in a large series of RT from the French Innovative Leukemia Organization (FILO). Methods: Biopsy-confirmed RT (limited to DLBCL and excluding Hodgkin lymphoma) diagnosed from 2001 to 2018 were identified from eight FILO centers. Clinical and biological characteristics of CLL and RT at diagnosis, including cytogenetics, clonal relation with the pre-existing CLL, Epstein-Barr virus (EBV) status, cell of origin (COO) analyzed by immunohistochemistry and RT score (Tsimberidou AM et al, J Clin Oncol, 2006) were analyzed as well as treatment and outcomes. Overall survivals (OS) were defined as time from CLL and RT diagnosis to death from any cause and analyzed using the Kaplan-Meier method. Statistical analyses were performed with SAS version 9.4. Results: A total of 70 CLL pts who developed RT were identified. The median age at CLL diagnosis was 62 years old (range 35-82), and 50 (71.4 %) were male. The median time to transformation was 5.5 years (range 0 to 22 years), with 12 simultaneous diagnosis of CLL and RT. Prior to RT, 20 (29%) pts had not been treated for CLL, 50 received one (n=21) or more (n= 29) line of treatment ; 6 pts had received a novel agent (ibrutinib, idelalisib or venetoclax). The median age at RT diagnosis was 68 years old (range 42-88). All biopsies were centrally reviewed; 38/58 pts (66%) had elevated LDH (>1.5N) ; 35/65 pts (54 %) had bulky disease (≥ 5 cm); 10/54 (18.5%) pts had del(17p) or TP53 mutation ; 9/42 pts (21%) had a complex karyotype (at least 3 abnormalities). The CLL and RT were clonally related in 27/27 (100%) tested pts. COO by Hans algorithm was non germinal center B cell-like (GCB) in 26/28 pts (93%). EBV was positive or detected in 5/40 (12.5%) pts. The median of Ki67 positivity was 70% (range 30% to 100%). The RT score (based at RT diagnosis on ECOG performance status 2-4, LDH >1.5 x normal, platelets<100 x 109/L, tumor size >5 cm and >1 prior therapy for CLL) was : low risk in 17 pts (31%), low-intermediate risk in 10 pts (19%), high-intermediate risk in 14 pts (25%) and high risk in 14 pts (25%). The most common first-line treatment of RT was immunochemotherapy (n=57, 87%) including R-CHOP-like regimen (n=48, 73%). Autologous or allogeneic transplantation was performed for 7 pts (11%). Response to first-line treatment was complete or partial response in 26 pts (40%), and stable disease or progression in 39 pts (60%). After a median follow-up of 8 years, 51/64 pts (80%) have died. The main causes of death were progressive DLBCL (n=36, 71%), infection (n=8, 16%) or progressive CLL (n=2, 4%). The median OS of the cohort from CLL and RT diagnosis (Figure 1) were 7.8 years and 9.5 months, respectively. In univariate analysis, patients with TP53 disruption at CLL stage, low platelets count, elevated LDH, elevated beta2-microglobulin, high ECOG score, high RT score, EBV positivity and absence of response to first-line RT treatment had worse OS. The ECOG score, platelets count and TP53 disruption remain significant in multivariate Cox-regression. Last, we compared the clinical and biological parameters of two Richter groups defined as: (i) short-term survivors (<12 months, n = 34) and (ii) long-term survivors (>48 months, n = 18). Long survival was significantly associated with elevated platelets count, low LDH, low ECOG, low RT score and response to RT first-line treatment. Discussion: The clinical outcomes of RT patients is poor and novel treatment options are needed. However, a group of long-term survivors was identified, characterized by elevated platelets count, low LDH, low ECOG, low RT score and response to immunochemotherapy. Disclosures Leblond: Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees. Cymbalista:Janssen: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; Sunesis: Research Funding; Roche: Research Funding; Abbvie: Honoraria. Guièze:Abbvie: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Roche: Honoraria. Broseus:Janssen: Honoraria; Gilead: Honoraria; Novartis: Research Funding. Feugier:gilead: Honoraria, Research Funding, Speakers Bureau; janssen: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau.

scholarly journals Severe aplastic anemia: allogeneic bone marrow transplantation as first-line treatment

2018 ◽  
Vol 2 (15) ◽  
pp. 2020-2028 ◽  
Author(s):  
George E. Georges ◽  
Kris Doney ◽  
Rainer Storb
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Marrow Transplantation ◽  
Severe Aplastic Anemia ◽  
Unrelated Donor ◽  
Line Treatment ◽  
First Line ◽  
Matched Unrelated Donor ◽  
First Line Treatment

Abstract Treatment of severe aplastic anemia has improved significantly over the past 4 decades. This review will summarize the key areas of progress in the use of allogeneic hematopoietic cell transplantation and nontransplant immunosuppressive therapy (IST) for the treatment of aplastic anemia and then summarize the recommendations for first-line treatment. Based on recent data, we argue that guidelines for the initial treatment of patients with newly diagnosed severe aplastic anemia require revision. At the time of diagnosis, before beginning treatment, HLA typing should be done to identify a marrow donor among family members or in the unrelated donor registries, and a marrow transplant should be considered first-line therapy. The priority order of donor source for bone marrow transplantation is: (1) HLA-identical sibling, (2) HLA-matched unrelated donor, and (3) HLA-haploidentical donor if an HLA-matched unrelated donor is not rapidly available. Each of these donor marrow sources may be preferable to nontransplant IST. We make this recommendation because of the long-term persistent risk for disease relapse and secondary myelodysplastic syndrome or acute myeloid leukemia with the use of nontransplant IST for patients with aplastic anemia. In contrast, marrow transplantation is associated with high cure rates of aplastic anemia and a relatively low risk for graft-versus-host disease, with many patients now living for decades without the risk for disease recurrence or the development of clonal disorders. Implementation of this first-line treatment strategy will provide patients with severe aplastic anemia the best chance of long-term disease-free survival.

scholarly journals Management of Pearly Penile Papules: A Review of the Literature

2019 ◽  
Vol 24 (1) ◽  
pp. 79-85 ◽  
Author(s):  
Anthony D. Honigman ◽  
Danielle P. Dubin ◽  
Justin Chu ◽  
Matthew J. Lin
Keyword(s):  
Psychological Distress ◽  
Long Term Results ◽  
Treatment Modalities ◽  
Line Treatment ◽  
Review Of The Literature ◽  
First Line ◽  
Cosmetic Outcomes ◽  
First Line Treatment ◽  
Ablative Laser

Pearly penile papules (PPPs) are benign, dome-shaped lesions found around the corona of the penis. Despite being asymptomatic and benign in nature, the appearance of PPPs may cause a great deal of psychological distress to both the patient and their sexual partner. While patient reassurance may be the first-line treatment, several other treatment modalities including cryotherapy, electrodessication and curettage, and laser therapy have all been used to treat PPPs in order to achieve a cosmetic outcome that satisfies the patient. Based on the evaluation of the existing literature, ablative laser therapies offer satisfactory cosmetic outcomes with good long-term results.

scholarly journals RADI-08. A SURVEY BASED STUDY OF BRAIN METASTASES MANAGEMENT FOR PATIENTS WITH NON-SMALL CELL LUNG CANCERS OR MELANOMA

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i23-i23
Author(s):  
Chin Heng Fong ◽  
Natasha Leighl ◽  
Marcus Butler ◽  
Mark Doherty ◽  
Timothy Kruser ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Systemic Therapy ◽  
Kinase Inhibitors ◽  
Standard Of Care ◽  
Line Treatment ◽  
First Line ◽  
Exact Test ◽  
Lung Cancers ◽  
Radiation Oncologists ◽  
First Line Treatment

Abstract INTRODUCTION: The standard of care for 1–4 brain metastases (BrM) is stereotactic radiosurgery (SRS), whereas whole brain radiation remains the standard treatment for extensive BrM, and surgical resection is appropriate in certain scenarios. Some newer systemic therapies such as tyrosine kinase inhibitors and immunotherapy have impressive CNS activity and are used by some practitioners either alone or in combination with other modalities as first-line treatment for BrM. We conducted a survey to ascertain current real-world practices for the treatment of BrM from NSCLC and melanoma. OBJECTIVES: Our study aimed to assess practice patterns of oncologists who treat BrM from NSCLC or melanoma. We also investigated the extent to which various clinical factors influence decision making. METHODOLOGY: We created 2 sets of surveys: one for Medical-/Clinical-/Neuro- oncologists and another for Radiation oncologists/Neurosurgeons. Surveys were conducted online or on-line. Following administration, data was tabulated and analyzed. Statistical analyses were performed using Fisher’s exact test. RESULTS: Of 361 respondents, 250 were Radiation oncologists/Neurosurgeons, and 111 were Medical-/Clinical-/Neuro- oncologists. For patients with 1–3 brain lesions, all &lt; 2cm, 34% of respondents recommended systemic therapy alone as first-line treatment. In contrast, only 15% recommend systemic therapy alone for &gt;9 lesions, at least one &gt; 2cm. Medical-/Clinical-/Neuro- oncologists were more likely to recommend systemic therapy alone compared to Radiation oncologists/ Neurosurgeons for 1–3 lesions, all &lt; 2cm (53% vs. 28%, p&lt; .0001). For patients with &gt; 9 BrM, one &gt;2cm diameter, Medical-/Clinical-/Neuro- oncologists were not significantly more likely to recommend systemic therapy alone (20% vs 13%, p=.11). DISCUSSION: Our results reveal that significant numbers of physicians recommend systemic therapy alone as first-line therapy in BrM and that management decisions correlate with a physician’s type of practice. These findings underscore the need for prospective clinical trials to direct appropriate BrM management.

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