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Autoimmune hepatitis treatment in the elderly: A systematic review

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World Journal of Gastroenterology 2019年第22期25卷 2809-2818页

作者： Marilena Durazzo Giulia Lupi Michela ScANDella Arianna Ferro Gabriella Gruden Department of Medical Sciences University of Turin

BACKGROUND Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease with a high risk of progression to liver cirrhosis. The initial treatment for AIH usually includes a steroid, with or without azathioprine. AIH can present at any age;however, the most effective and safe induction treatment for AIH in the elderly remains unclear. AIM To systematically review available data on both effectiveness and safety of AIH treatments in elderly subjects. METHODS To identify studies on AIH induction treatment in elderly patients (≥ 60 years of age), an electronic research was performed (PubMed, EMBASE and Cochrane Library databases) until February 2019. Eligible studies were selected through screening of titles and abstracts, followed by full-text critical evaluation. After risk of bias assessment, data on study designs, interventions, and outcomes were extracted and reviewed. RESULTS Among the 1736 retrieved papers, 15 studies were selected. Out of them, eight studies were excluded because of a critical risk of bias. The remaining seven studies included 789 patients and out of them 239 subjects were elders. First-line treatment was a steroid either alone or in combination with azathioprine in most patients (87.6%) and only one study investigated the effect of combined steroid and mycophenolate mofetil therapy. Standard therapy was effective in inducing remission in the elderly. Moreover, treatment failure and relapses occurred less often in the elderly compared to younger people.CONCLUSION Treatment of AIH is challenging in elderly patients. This systematic review confirms the efficacy and safety of standard induction treatment for AIH in the elderly. Available evidence is insufficient to draw any conclusion on the effect of novel AIH treatments in elderly subjects.

关键词： Autoimmune hepatitis Elderly patients Aged steroids Azathioprine Mycophenolate mofetil

Idiopathic sudden sensorineural hearing loss:Effectiveness of salvage treatment with low-dose intratympanic dexamethasone

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Journal of Otology 2021年第1期16卷 6-11页

作者： Pedro Salvador Francisco Moreira da Silva Rui Fonseca Department of Otorhinolaryngology Hospital Senhora da OliveiraGuimaraesPortugal

Objectives:To evaluate hearing outcome of salvage treatment with intratympanic steroids(ITS)in idiopathic sudden sensorineural hearing loss(ISSNHL)refractory to initial systemic steroid(SS)therapy.Material and methods:A retrospective medical chart review was conducted on 54 consecutive patients with ISSNHL refractory to SS.Salvage treatment with a low dose intratympanic dexamethasone(4 mg/ml)was offered after one week of primary treatment.Patients were divided into two groups:25 patients accepted ITS(treatment group)and 29 patients did not undergo additional treatment(control group).A pure tone average(PTA)gain of at least 10 dB was considered hearing improvement.Results:Hearing improvement rate was higher in ITS group compared to control group(40%vs.13.8%,p=0.035).A mean PTA improvement of 8.6±9.8 dB was observed in the ITS group and,whereas the control group had an average hearing gain of 0.7±2 dB(p<0.001).Audiometric analysis revealed a significant hearing gain in ITS group at all tested frequencies compared to control group(p<0.05).Analysis of the selected variables,identified intratympanic steroid treatment as the only independent prognostic factor for hearing improvement(OR=4.2,95%CI:1.1e15.7;p=0.04).Conclusion:Intratympanic low dose dexamethasone is effective in patients with incomplete hearing recovery after primary systemic steroid treatment.

关键词： Intratympanic steroids Salvage Sudden sensorineural hearing loss Idiopathic

Diagnosis and management of pediatric adrenal insufficiency

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世界儿科杂志:英文版 2016年第3期12卷 261-274页

作者： Ahmet Ucar Firdevs Bas Nurcin Saka Growth-Development and Pediatric Endocrine Unit Istanbul School of MedicineIstanbul UniversityTurkey

Background:Adrenal insufficiency(AI)is a wellknown cause of potentially life-threatening disorders.Defects at each level of the hypothalamic-pituitary-adrenal axis can impair adrenal function,leading to varying degrees of glucocorticoid(GC)deficiency.Iatrogenic AI induced by exogenous GCs is the most common cause of AI.The criteria for the diagnosis and management of iatrogenic AI,neonatal AI,and critical illness-related corticosteroid insuffi ciency(CIRCI)are not clear.Data sources:We reviewed the recent original publications and classical data from the literature,as well as the clinical,diagnostic and management strategies of pediatric AI.Results:Practical points in the diagnosis and management of AI with an emphasis on iatrogenic AI,neonatal AI,and CIRCI are provided.Given the lack of sensitive and practical biochemical tests for diagnosis of subtle AI,GC treatment has to be tailored to highly suggestive clinical symptoms and signs.Treatment of adrenal crisis is well standardized and patients almost invariably respond well to therapy.It is mainly the delay in treatment that is responsible for mortality in adrenal crisis.Conclusion:Education of patients and health care professionals is mandatory for timely interventions for patients with adrenal crisis.

关键词： adrenal insuffi ciency critical illness hypothalamo-pituitary-adrenal axis iatrogenic steroids

Breast cancer stem cells: The role of sex steroid receptors

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World Journal of Stem Cells 2019年第9期11卷 594-603页

作者： Pia Giovannelli Marzia Di Donato Giovanni Galasso Erika Di Zazzo Nicola Medici Antonio Bilancio Antimo Migliaccio Gabriella Castoria Department of Precision Medicine University of Campania "L.Vanvitelli"

Breast cancer(BC)is the most common cancer among women,and current available therapies often have high success rates.Nevertheless,BC might acquire drug resistance and sometimes relapse.Current knowledge about the most aggressive forms of BC points to the role of specific cells with stem properties located within BC,the so-called“BC stem cells”(BCSCs).The role of BCSCs in cancer formation,growth,invasiveness,therapy resistance and tumor recurrence is becoming increasingly clear.The growth and metastatic properties of BCSCs are regulated by different pathways,which are only partially known.Sex steroid receptors(SSRs),which are involved in BC etiology and progression,promote BCSC proliferation,dedifferentiation and migration.However,in the literature,there is incomplete information about their roles.Particularly,there are contrasting conclusions about the expression and role of the classical BC hormonal biomarkers,such as estrogen receptor alpha(ERα),together with scant,albeit promising information concerning ER beta(ERβ)and androgen receptor(AR)properties that control different transduction pathways in BCSCs.In this review,we will discuss the role that SRs expressed in BCSCs play to BC progression and recurrence and how these findings have opened new therapeutic possibilities.

关键词： Breast cancer steroids Sex steroid receptors Cancer stem cells Therapeutic implications

Dexamethasone intravitreal implant(Ozurdex) in diabetic macular edema: real-world data versus clinical trials outcomes

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International Journal of Ophthalmology(English edition) 2021年第10期14卷 1571-1580页

作者： Pedro Neves Mário Ornelas Inês Matias João Rodrigues Margarida Santos Marco DutraMedeiros David Martins Department of Ophthalmology Centro Hospitalar de SetúbalSetúbal 2910-549Portugal Department of Ophthalmology Hospital BeatrizÂngeloLoures 2674-514Portugal Department of Ophthalmology Hospital da Luz SetúbalSetúbal 2900-722Portugal Department of Ophthalmology Centro Hospitalar Lisboa CentralFaculdade de Ciências MédicasNOVA University of LisbonLisbon 1990-237Portugal

AIM: To investigate the safety and efficacy of intravitreal dexamethasone implants(Ozurdex?/DEX) in patients with diabetic macular edema(DME) either na?ve or nonna?ve to anti-VEGF therapies who switched to DEX implant independent of response to anti-vascular endothelial growth factors(anti-VEGFs).METHODS: This was an audit retrospective review of medical records of patients with DME who switched to the DEX intravitreal implant. Patients were divided into 2 groups: patients na?ve to antiangiogenic therapy and patients who were previously treated with anti-VEGFs. Data regarding demographics, changes in mean best-corrected visual acuity(BCVA), central macular thickness(CMT), and intraocular pressure(IOP) was collected over 6 mo. The demographic data mean changes in BCVA, CMT, and IOP were compared. Six-month follow-up data of 47 patients(57 eyes), who either switched to DEX implant irrespective of response to previous treatments or were treatment na?ve before receiving DEX implant, was collected.RESULTS: Improvement in mean BCVA was observed from 1-4 mo after injection with a decreased effect at month 6 as expected, with better outcomes in na?ve compared to non-na?ve patients. A statistically relevant decrease in mean CMT was observed during the follow-up period. An increase in mean IOP was observed in the first 2 mo after DEX therapy. The mean number of injections of the overall population during the 6 mo was 1.3. A subgroup analysis showed no relevant difference between phakic versus pseudophakic patients relative to measured outcomes. There was no cataract progression during the follow-up period and no adverse events reported.CONCLUSION: This real-life setting study shows that intravitreal DEX implant is effective and safe. The timings of greater therapeutic impact are concordant with previous studies and suggest that earlier treatment with corticosteroids may have an additional benefit in na?ve patients.

关键词： anti-VEGF therapy diabetic macular edema dexamethasone intravitreal implant na?ve eyes steroids

Medical management of COVID-19 clinic

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The Journal of Biomedical Research 2020年第6期34卷 416-421页

作者： Neha Mehta Renli Qiao Division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA.

The start of the global pandemic secondary to the novel SARS-CoV-2 virus was a time of uncertainty and fear as it claimed the lives of many across the world.Since then,there has been a plethora of research designs and trials in order to understand what we can do to stop the spread of the disease.Scientists and health care providers have utilized old medications and revamped them for current use such a convalescent plasma and steroids,as well as creating novel therapeutics,some with promising results.In this article,we review the major therapeutic options currently available and look into what the future still holds in order to further our understanding of this mysterious disease.

关键词： COVID-19 treatment steroids remdesivir vaccine

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World Journal of Clinical Cases 2020年第20期8卷 4807-4815页

作者： Ci Tian Yang Lv Shu Li Dai-Dai Wang Yi Bai Fang Zhou Qing-Bian Ma Department of Emergency Medicine Peking University Third HospitalBeijing 100191China Department of Orthopedics Peking University Third HospitalBeijing 100191China

BACKGROUND Acute traumatic spinal cord injury(ATSCI)usually results in disability,yet data on contemporary national trends of ATSCI incidence are limited.AIM To provide a systematic and basic theoretical basis for improving the treatment of acute spinal cord injury.METHODS Data from the Peking University Third Hospital Inpatient Sample databases were analyzed.A total of 304 patients with ATSCI were included from 2012 to 2017.The epidemiological data,treatment,complications and clinical outcomes of these patients were reviewed.RESULTS Of the 304 patients,257(84.5%)were male,and 75%of the patients were 55 years old or younger.135 patients had improved follow-up American Spinal Injury Association(ASIA)grades(44.4%).Only 14 patients with ASIA grade A improved.A statistically significant difference in prognosis between patients who underwent surgery within 72 h and those who underwent surgery after 72 h was observed(P<0.05).Surgery within 72 h resulted in better prognosis.The Steroid group and the Non-Steroid group showed a significant difference in outcome among patients with ASIA grades A and B(P<0.05).Patients with pneumonia had a poorer prognosis than patients without pneumonia(P<0.05).Surgery within 72 h resulted in better prognosis.CONCLUSION This study found that there was no significant difference in hospitalization time and prognosis between the Steroid group and the Non-Steroid group,but the patients with severe spinal cord injury(ASIA grades A and B)who underwent surgery combined with steroid therapy had a better prognosis than those who underwent surgery alone.The disastrous consequences of ATSCI and lack of consensus on the management strategy are obvious.Further improvements in treatment planns are needed in order to obtain more reliable functional outcomes.

关键词： Acute spinal cord injury Trauma Surgery American Spinal Injury Association steroids Prognosis

Conventional therapy for moderate to severe inflammatory bowel disease: A systematic literature review

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World Journal of Gastroenterology 2019年第9期25卷 1142-1157页

作者： Adérson Omar Mourao Cintra Damiao Matheus Freitas Cardoso de Azevedo Alexandre de Sousa Carlos Marcela Yumi Wada Taciana Valéria Marcolino Silva Flávio de Castro Feitosa Department of Gastroenterology University of Sao Paulo School of Medicine Department of Medical Affairs Takeda Pharmaceuticals

BACKGROUND Despite the advent of biological drugs, conventional therapy continues to be used in moderate to severe inflammatory bowel disease(MS-IBD). This study hypothesized that as a standard of treatment and the primary alternative to biologics, conventional therapy should present robust effectiveness results in IBD outcomes.AIM To investigate the effectiveness of conventional therapy for MS-IBD.METHODS A systematic review with no time limit was conducted in July 2017 through the Cochrane Collaboration, MEDLINE, and LILACS databases. The inclusion criteria encompassed meta-analyses, systematic reviews, randomized clinical trials, observational and case-control studies concerning conventional therapy in adult patients with MS-IBD, including Crohn's disease(CD) and ulcerative colitis(UC). Corticosteroids(prednisone, hydrocortisone, budesonide, prednisolone,dexamethasone), 5-aminosalicylic acid(5-ASA) derivatives(mesalazine and sulfasalazine) and immunosuppressants [azathioprine(AZA), methotrexate(MTX), mycophenolate, cyclosporine, tacrolimus, 6-mercaptopurine(6-MP)] were considered conventional therapy. The exclusion criteria were sample size below50; narrative reviews; specific subpopulations(e.g., pregnant women,comorbidities); studies on postoperative IBD; and languages other than English,Spanish, French or Portuguese. The primary outcome measures were clinical remission(induction or maintenance), clinical response and mucosal healing. As secondary outcomes, fecal calprotectin, hospitalization, death, and surgeries were analyzed. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation criteria.RESULTS The search strategy identified 1995 citations, of which 27 were considered eligible(7 meta-analyses, 20 individual studies). For induction of clinical remission, four meta-analyses were selected(AZA and 6-MP showed no advantage over placebo,MTX or 5-ASA in CD; MTX showed no statistically significant difference versus placebo, 6-MP, or 5-ASA in UC; tacr

关键词： Inflammatory bowel diseases steroids Sulfasalazine Mesalamine Azathioprine Methotrexate Mycophenolic acid Cyclosporine Tacrolimus 6-Mercaptopurine

The role of serratiopeptidase in the resolution of inflammation

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Asian Journal of Pharmaceutical Sciences 2017年第3期12卷 209-215页

作者： Manju Tiwari Department of Biochemistry and Genetics Barkatullah University

Inflammation remains a key event during most of the diseases and physiological imbalance. Acute inflammation is an essential physiological event by immune system for a protective measure to remove cause of inflammation and failure of resolution lead to chronic inflammation. Over a period of time, a number of drugs mostly chemical have been deployed to combat acute and chronic inflammation. Recently, enzyme based anti-inflammatory drugs became popular over conventional chemical based drugs. Serratiopeptidase, a proteolytic enzyme from trypsin family, possesses tremendous scope in combating inflammation. Serine protease possesses a higher affinity for cyclooxygenase(COX-Ⅰ and COX-Ⅱ), a key enzyme associated with production of different inflammatory mediators including interleukins(IL),prostaglandins(PGs) and thromboxane(TXs) etc. Currently, arthritis, sinusitis, bronchitis,fibrocystic breast disease, and carpal tunnel syndrome, etc. are the leading inflammatory disorders that affected the entire the globe. In order to conquer inflammation, both acute and chronic world, physician mostly relies on conventional drugs. The most common drugs to combat acute inflammation are Nonsteroidal anti-inflammatory drugs(NSAIDs) alone and or in combination with other drugs. However, during chronic inflammation, NSAIDs are often used with steroidal drugs such as autoimmune disorders. These drugs possess several limitations such as side effects, ADR, etc. In order to overcome these limitations and complications, enzyme based drugs(anti-inflammatory) emerged, and aim for a new high since the last decade. Serine protease, the largest proteolytic family has been reported for several therapeutic applications, including anti-inflammatory. Serratiopeptidase is a leading enzyme which has a very long history in medical as an effective anti-inflammatory drug. Current study emphasizes present scenario and future prospect of serratiopeptidase as an antiinflammatory drug. The study also illustrates a comparative analysis of conventional drugs a

关键词： Inflammation Cyclooxygenase NSAIDs Serratiopeptidase steroids Enzyme therapeutics