Use Of Corticosteroids In Treatment Research Articles

Implementation of Recommendations on the Use of Corticosteroids in Severe COVID-19

Research diversity and representativeness are paramount in building trust, generating valid biomedical knowledge, and possibly in implementing clinical guidelines. To compare variations over time and across World Health Organization (WHO) geographic regions of corticosteroid use for treatment of severe COVID-19; secondary objectives were to evaluate the association between the timing of publication of the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial (June 2020) and the WHO guidelines for corticosteroids (September 2020) and the temporal trends observed in corticosteroid use by region and to describe the geographic distribution of the recruitment in clinical trials that informed the WHO recommendation. This prospective cohort study of 434 851 patients was conducted between January 31, 2020, and September 2, 2022, in 63 countries worldwide. The data were collected under the auspices of the International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC)-WHO Clinical Characterisation Protocol for Severe Emerging Infections. Analyses were restricted to patients hospitalized for severe COVID-19 (a subset of the ISARIC data set). Corticosteroid use as reported to the ISARIC-WHO Clinical Characterisation Protocol for Severe Emerging Infections. Number and percentage of patients hospitalized with severe COVID-19 who received corticosteroids by time period and by WHO geographic region. Among 434 851 patients with confirmed severe or critical COVID-19 for whom receipt of corticosteroids could be ascertained (median [IQR] age, 61.0 [48.0-74.0] years; 53.0% male), 174 307 (40.1%) received corticosteroids during the study period. Of the participants in clinical trials that informed the guideline, 91.6% were recruited from the United Kingdom. In all regions, corticosteroid use for severe COVID-19 increased, but this increase corresponded to the timing of the RECOVERY trial (time-interruption coefficient 1.0 [95% CI, 0.9-1.2]) and WHO guideline (time-interruption coefficient 1.9 [95% CI, 1.7-2.0]) publications only in Europe. At the end of the study period, corticosteroid use for treatment of severe COVID-19 was highest in the Americas (5421 of 6095 [88.9%]; 95% CI, 87.7-90.2) and lowest in Africa (31 588 of 185 191 [17.1%]; 95% CI, 16.8-17.3). The results of this cohort study showed that implementation of the guidelines for use of corticosteroids in the treatment of severe COVID-19 varied geographically. Uptake of corticosteroid treatment was lower in regions with limited clinical trial involvement. Improving research diversity and representativeness may facilitate timely knowledge uptake and guideline implementation.

Therapeutic and Side Effects of Intra-articular and Intraperitoneal Injections of Corticosteroids on Temporomandibular Joint Inflammation: A Review Study

Background and Objectives This study aims to investigate the therapeutic effects and side effects of intraarticular (IA) and intra-peritoneal (IP) injections of corticosteroids on temporomandibular joint (TMJ) inflammation Subjects and Methods This is a review study that was conducted on related studies published from 1990 to 2022 which were searched in Web of Science, PubMed, Scopus, Google Scholar, SID, Magiran and IranMedex using the keywords “temporomandibular joint”, “intra-articular injection”, “corticosteroid”, “adverse effects”, “juvenile arthritis”, “osteoarthritis”, “ Juvenile idiopathic arthritis”,”degenerative joint disorders”, and “temporomandibular joint disorders”. Results A total of 13 studies met the inclusion criteria. Two studies were related to IP injection, 8 related to IA injection, two studies compared the effect of IA and IP drug injection, and one study investigated the TMJ arthrocentesis and IP drug injection. In 4 studies, the aim was to compare the effectivness of corticosteroids and hyaluronic acid in improving temporomandibular disorders. Nine studies found that the use of corticosteroids is beneficial for the treatment of TMJ inflammation, and 7 studies reported complications such as condylar resorption. Conclusion Since the use of corticosteroids in treatment of TMJ disorders is not without complications, there is a need to conduct extensive studies on various drugs with anti-inflammatory effects and lowest side effects to replace them with corticosteroids.

Efficacy of corticosteroids as an adjunctive therapy in the treatment of community-acquired pneumonia: a systematic review and meta-analysis

The objective of this study was to systematically evaluate the clinical efficacy of the complementary use of corticosteroids in the treatment of community-acquired pneumonia (CAP). We searched all relevant documents in five scientific databases from inception to June 2022 to collect clinical trials (randomized controlled trials and controlled trials) reporting on the adjunctive use of corticosteroids in CAP treatment. The primary outcome was mortality, and secondary outcomes included the time to clinical stability, therapeutic efficacy, duration of antibiotic treatment and length of hospital/ICU stay. Therapeutic efficacy was defined as the rate of achieving clinical recovery with no fever, improvement or disappearance of cough. Clinical stability was defined by improvements in laboratory values. Two researchers independently screened the literature according to the inclusion and exclusion criteria, extracted data and evaluated the quality of literature. Statistical analysis and meta-analysis of intervention measures and indicators were performed with IBM SPSS and RevMan 5.4 software. Nine randomized controlled trials comprising 2673 participants with CAP (1335 in the corticosteroid group and 1338 in the control group) were identified and included in this study. The mean cumulative corticosteroid dose and treatment duration were 298.00±287.140 mg and 5.22±1.787 days, respectively. Corticosteroid treatment was not associated with a significant decrease in mortality (RR; 95% CI, 0.96 [0.67–1.38], P=0.83). Because of the low number of included patients in our study, more studies with larger sample sizes and high-quality randomized, double-blind controlled trials are needed to confirm the results.

Clinicopathological Study of Mucormycosis in COVID-19 Patients: Experience From a Tertiary Care Center in South India.

Background: The coronavirus disease 2019 (COVID-19) pandemic has taken the world to different dimensions. With the surge of the second wave in India, the number of cases with mucormycosis has increased. Mucormycosis is a potentially life-threatening, opportunistic, invasive, fungal infection that can occur in immunocompromised states. The aim of the study is to analyze the clinicopathological parameters of patients with mucormycosis in the surge of the second wave of COVID-19.Materials and Methods: All cases of mucormycosis reported in the Department of Pathology in a tertiary care centre in South India from March 2021 to June 2021 were included in the study. The patient details were retrieved from the Medical Records section. The patient characteristics, location, associated comorbidities, management and treatment outcomes were analyzed and compared to similar studies reported worldwide.Results: Of 58 cases, 38 (65%) were males and 20 (35%) were females. The ages ranged from 34 to 77 years. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in 46 patients in reverse transcription polymerase chain reaction (RT-PCR) with high-resolution computed tomography (HRCT) Chest changes noted in 54 patients. Associated comorbidities were noted in 52 patients, with uncontrolled diabetes mellitus (46 patients; 88%) being the most common. Location was commonly in nasal and paranasal sinuses (43%), followed by orbital (2%), cerebral (10%) and pulmonary (8%) areas. Among the paranasal sinuses, the maxillary sinus was commonly involved. Mixed fungal infections (Aspergillus sp. and Candida sp.) were noted in eight (14%) cases. Oxygen therapy was given in 85% of cases; 30% of cases needed ventilator support; corticosteroid therapy was initiated in 49 patients, tocilizumab in six patients as treatment for mucormycosis. Amphotericin B was administered in 59% of patients based on clinical findings alone. After histopathological confirmation, 90% of them received amphotericin. Functional endoscopic sinus surgery (FESS) was done in 96% of cases, among them 45% underwent extensive surgical debridement and 15% underwent orbital decompression. Orbital exenteration (2%) was the other modality of management.Conclusion: Detailed analysis of clinicopathological features suggests the possibilities of immunosuppression (due to diabetes and use of corticosteroids in treatment of COVID-19) and COVID-19 (endothelial damage, cytokine storm) being the pathogenesis associated with the sudden surge of mucormycosis.

Use of Corticosteroids in Prenatal Treatment of Congenital Pulmonary Adenomatoid Malformation: Integrative Review.

To review data on the use of corticosteroids for the treatment of fetuses with high-risk congenital pulmonary adenomatoid malformation (CPAM). Integrative review based on the literature available on MEDLINE and LILACS, including articles published until November, 2020. The initial search resulted in 87 articles, 4 of which were selected for analysis, with all of them being retrospective descriptive observational studies. In the group of fetuses that received only a single corticosteroid cycle, the hydrops resolution rate was 70%, and the survival rate was 83.8%. In fetuses treated with 2 or more cycles of corticosteroids, there was an improvement in the condition of hydrops or edema in a single body compartment in 47%, and survival of 81.8% of the fetuses. The use of corticosteroids for the prenatal treatment of high-risk CPAM appears to be associated with an improvement in perinatal outcomes.

"MATH+" Multi-Modal Hospital Treatment Protocol for COVID-19 Infection: Clinical and Scientific Rationale.

In December 2019, coronavirus disease 2019 (COVID-19), a severe respiratory illness caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The greatest impact that COVID-19 had was on intensive care units (ICUs), given that approximately 20% of hospitalized cases developed acute respiratory failure (ARF) requiring ICU admission. Based on the assumption that COVID-19 represented a viral pneumonia and no anti-coronaviral therapy existed, nearly all national and international health care societies recommended “supportive care only” avoiding other therapies outside of randomized controlled trials, with a specific prohibition against the use of corticosteroids in treatment. However, early studies of COVID-19-associated ARF reported inexplicably high mortality rates, with frequent prolonged durations of mechanical ventilation (MV), even from centers expert in such supportive care strategies. These reports led the authors to form a clinical expert panel called the Front-Line COVID-19 Critical Care Alliance (www.flccc.net). The panel collaboratively reviewed the emerging clinical, radiographic, and pathological reports of COVID-19 while initiating multiple discussions among a wide clinical network of front-line clinical ICU experts from initial outbreak areas in China, Italy, and New York. Based on the shared early impressions of “what was working and what wasn’t working”, the increasing medical journal publications and the rapidly accumulating personal clinical experiences with COVID-19 patients, a treatment protocol was created for the hospitalized patients based on the core therapies of methylprednisolone, ascorbic acid, thiamine, heparin and non-antiviral co-interventions (MATH+). This manuscript reviews the scientific and clinical rationale behind MATH+ based on published in-vitro, pre-clinical, and clinical data in support of each medicine, with a special emphasis of studies supporting their use in the treatment of patients with viral syndromes and COVID-19 specifically.

“STUDY OF INVASIVE MUCORMYCOSIS REPORTED ON HISTOPATHOLOGY IN POST COVID-19 CASES AT A TERTIARY CARE HOSPITAL OF CENTRAL INDIA: A CASE SERIES”

Background: Coronavirus disease 2019 (Covid-19) is an infection caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In recent studies observed that, in Covid-19 infected patient who treated with widespread use of broad-spectrum antibiotic or steroid and recovered developed secondary bacterial or fungal infection in 8%. Mucormycosis infection of the sinuses is a form of life-threatening invasive fungal sinusitis that typically affects immunocompromised individuals with an impaired neutrophilic response. Aims: 1) To study the histopathological features in cases labelled as invasive fungal sinusitis. 2) To study the association of age, gender, positive history of Covid-19 infection, co-morbidities, use of corticosteroids and clinical presentation of cases of mucormycosis. 3) To compare our observations with the study of other authors. Materials And Methods: A cross – sectional observational study was undertaken at Chhattisgarh Institute of Medical Sciences, Bilaspur, Chhattisgarh in Department of Pathology, over a period of 6 months from May to October 2021. Biopsies received were then processed as per the standard operating procedure and stained with H & E staining and observed under microscope. Results: On histopathological examination, we observed that the lesional tissue in the nasal biopsy/ maxillary sinus biopsy was lined by respiratory epithelium and showed numerous broad, non – sepatate hyphae, at places showing branching. Few of the cases showed focal spore formation. Conclusions: This study was useful in understanding histopathological features of this not–so–common fungal infection. This study also subtly pointed towards the demerits of inadvertent use of corticosteroids in treatment of Covid-19 patients, especially in those with co-morbidities like diabetes mellitus and elderly patients. The need of the hour, therefore, is to have “customized” treatment for every patient

Corticosteroid use in ARDS and its application to evolving therapeutics for coronavirus disease 2019 (COVID-19): A systematic review.

Data regarding the use of corticosteroids for treatment of acute respiratory distress syndrome (ARDS) are conflicting. As the coronavirus disease 2019 (COVID‐19) pandemic progresses, more literature supporting the use of corticosteroids for COVID‐19 and non‐COVID‐19 ARDS have emerged. Glucocorticoids are proposed to attenuate the inflammatory response and prevent progression to the fibroproliferative phase of ARDS through their multiple mechanisms and anti‐inflammatory properties. The purpose of this systematic review was to comprehensively evaluate the literature surrounding corticosteroid use in ARDS (non‐COVID‐19 and COVID‐19) in addition to a narrative review of clinical considerations of corticosteroid use in these patient populations. OVID Medline and EMBASE were searched. Randomized controlled trials evaluating the use of corticosteroids for COVID‐19 and non‐COVID‐19 ARDS in adult patients on mortality outcomes were included. Risk of bias was assessed with the Risk of Bias 2.0 tool. There were 388 studies identified, 15 of which met the inclusion criteria that included a total of 8877 patients. The studies included in our review reported a mortality benefit in 6/15 (40%) studies with benefit being seen at varying time points of mortality follow‐up (ICU survival, hospital, and 28 and 60 days) in the COVID‐19 and non‐COVID‐19 ARDS studies. The two non‐COVID19 trials assessing lung injury score improvements found that corticosteroids led to significant improvements with corticosteroid use. The number of mechanical ventilation‐free days significantly were found to be increased with the use of corticosteroids in all four studies that assessed this outcome. Corticosteroids are associated with improvements in mortality and ventilator‐free days in critically ill patients with both COVID‐19 and non‐COVID‐19 ARDS, and evidence suggests their use should be encouraged in these settings. However, due to substantial differences in the corticosteroid regimens utilized in these trials, questions still remain regarding the optimal corticosteroid agent, dose, and duration in patients with ARDS.

Clinical and Scientific Rationale for the "MATH+" Hospital Treatment Protocol for COVID-19.

In December 2019, COVID-19, a severe respiratory illness caused by the new coronavirus SARS-CoV-2 (COVID-19) emerged in Wuhan, China. The greatest impact that COVID-19 had was on intensive care units (ICUs), given that approximately 20% of hospitalized cases developed acute respiratory failure (ARF) requiring ICU admission. Based on the assumption that COVID-19 represented a viral pneumonia and no anti-coronaviral therapy existed, nearly all national and international health care societies' recommended "supportive care only" avoiding other therapies outside of randomized controlled trials, with a specific prohibition against the use of corticosteroids in treatment. However, early studies of COVID-19-associated ARF reported inexplicably high mortality rates, with frequent prolonged durations of mechanical ventilation (MV), even from centers expert in such supportive care strategies. These reports led the authors to form a clinical expert panel called the Front-Line COVID-19 Critical Care Alliance (www.flccc.net). The panel collaboratively reviewed the emerging clinical, radiographic, and pathological reports of COVID-19 while initiating multiple discussions among a wide clinical network of front-line clinical ICU experts from initial outbreak areas in China, Italy, and New York. Based on the shared early impressions of "what was working and what wasn't working," the increasing medical journal publications and the rapidly accumulating personal clinical experiences with COVID-19 patients, a treatment protocol was created for the hospitalized patients based on the core therapies of methylprednisolone, ascorbic acid, thiamine, heparin and co-interventions (MATH+). This manuscript reviews the scientific and clinical rationale behind MATH+ based on published in-vitro, pre-clinical, and clinical data in support of each medicine, with a special emphasis of studies supporting their use in the treatment of patients with viral syndromes and COVID-19 specifically. The review concludes with a comparison of published multi-national mortality data with MATH+ center outcomes.

S1436 Outcome of the Use of Corticosteroids for Treatment of Autoimmune Pancreatitis (AIP) in a COVID-19 Patient

INTRODUCTION: Autoimmune Pancreatitis (AIP) is a steroid-responsive disease of the pancreas. Due to poor outcomes in severe acute respiratory syndrome (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV) outbreaks, the World Health Organization (WHO) advises against the use of corticosteroids in the treatment of 2019 Coronavirus Disease (COVID-19) except if steroid therapy is required for coexisting illness. We present a case of uncontrolled AIP which was treated with high dose steroids while the patient was hospitalized with COVID-19. CASE DESCRIPTION/METHODS: A 53-year-old male was hospitalized with COVID-19 and uncontrolled AIP. The patient had elevated IgG4 levels and negative work up for other etiology of pancreatitis in the past and was already taking prednisone 40 mg daily due to a recent AIP exacerbation. On physical exam, temperature of 101 F, heart rate 101 beats/minute, respiratory rate 20 breaths/minute while blood pressure was normal. Tenderness in the epigastric region was noted. Labs showed Hct 35.8%, WBC 12.32 thousand/uL, BUN 9 mg/dL, lipase 530 u/L and normal LFTs. CT abdomen showed severe necrotizing pancreatitis with infected necrosis (multiloculated collections of gas and fluid) (Image 1). Chest imaging showed bibasilar infiltrates consistent with COVID-19 pneumonia (Image 2). Patient was continued on steroids, started on meropenem, and supportive treatment for COVID-19. Due to persistent abdominal pain and inability to tolerate oral intake, the patient underwent CT-guided percutaneous drainage of the necrotic collection. Azathioprine (AZA) was added to treatment regimen due to uncontrolled AIP despite steroid therapy. Patient recovered clinically without need for oxygen supplementation or further complication from COVID-19. He was discharged from the hospital with a short antibiotic course, a prescription to continue AZA and prednisone 40 mg with plan to taper dose by 5 mg per week. He returned home to continue quarantine which he completed without problems. DISCUSSION: Despite having multiple risk factors associated with poor outcomes in COVID-19 (age greater than 45 years, male gender, comorbidity due to uncontrolled AIP and immunosupression with steroid treatment), our patient experienced complete resolution of the illness with supportive measures. Our case supports current recommendations advocating steroid therapy for co-existing diseases in patients with COVID-19.Figure 1.: Image 1. CT scan abdomen shows multiloculated ill-defined of herterogeneous consistency as well as presence of gas pockets in the pancreatic and peri-pancreatic tissues, consistent with infected pancreatic necrotic collection in (A) and (B).Figure 2.: Image 2: Bibasilar lower lung infiltrates seen on CT scan chest (A) and Chest X-ray PA view (B), consistent with COVID-19 pneumonia.

A Sarcoidosis Patient Presents with Adrenal Insufficiency: A Standardized Patient Scenario for Medical Students and Residents.

IntroductionThe widespread use of corticosteroids for treatment of inflammatory conditions has resulted in the need to promptly recognize drug-induced adrenal insufficiency. This scenario was inspired by an actual case and aims to enhance critical thinking. Our case is unique as we use a case-based format with written tests to track progress.MethodsA pre-assessment was conducted to measure baseline knowledge with residents and medical students. A standardized patient played a 70-year-old female with sarcoidosis who was in the emergency department with weakness and fatigue. The learners obtained her history whereby they discovered that she had recently stopped taking prednisone. They identified adrenal insufficiency and reinstated glucocorticoid therapy. The scenario lasted 10 minutes after which there were a debriefing session and post-debriefing assessment. All were completed in under one hour.ResultsOur pre-scenario assessment revealed that all learners had less knowledge of adrenal insufficiency than thyroid disease with average scores of 66.63% and 91.25%, respectively. The average score of the adrenal insufficiency test increased from 66.63% to 87.45% on the post-debriefing assessment and the largest improvement was seen in first-year residents. Assessments measured via the Likert scale determined that all learners found the case well-devised to contribute to their understanding of adrenal insufficiency.DiscussionThe largest improvement unexpectedly was seen in first-year residents which may be due to variations in repetition and retention of medical knowledge in the months prior to starting residency. This module is best suited for first-year internal medicine, family medicine, and emergency medicine residents and upper-level medical students.

Clinical Audit for Use of Corticosteroids in Treatment of Nervous System Infections

Abstract Background: Anti-inflammatory therapy is indicated for CNS infection. Corticosteroids are the most valuable anti-inflammatory drugs for CNS disease. They reduce CNS edema via their action on blood vessels, and they produce anti-inflammatory effects via their action on neutrophils and inhibition of cytokine synthesis.Aim of the Study: To assess how much the adopted protocol of using corticosteroids in management of CNS infections is implemented in Assiut University Children Hospital (A.U.C.H).Patients and Methods: Retrospective study was conducted on patients admitted to Emergency unit, intermediate care unit, pediatric intensive care unit and department of neurology at Assiut University Children Hospital during the period from January 2016 to December 2016. Data were collected and compared to guidelines. Results: Corticosteroids was used in 100% of cases. Most of cases with CNS infection who received steroid treatment guided by treatment protocol showed marked improvement in GCS score, tendon reflexes, muscle tone and convulsions.Conclusion: Corticosteroids are usually the primary drugs used to treat immune-mediated disorders of the CNS, including corticosteroid-responsive meningitis and corticosteroid-responsive meningomyelitis.

Clinical Audit Study for Use of Corticosteroids in Treatment of Nervous System Infections

Abstract Background: Anti-inflammatory therapy is indicated for CNS infection. Corticosteroids are the most valuable anti-inflammatory drugs for CNS disease. They reduce CNS edema via their action on blood vessels, and they produce anti-inflammatory effects via their action on neutrophils and inhibition of cytokine synthesis.Aim of the Study: To assess how much the adopted protocol of using corticosteroids in management of CNS infections is implemented in Assiut University Children Hospital (A.U.C.H).Patients and Methods: Retrospective study was conducted on patients admitted to Emergency unit, intermediate care unit, pediatric intensive care unit and department of neurology at Assiut University Children Hospital during the period from January 2016 to December 2016. Data were collected and compared to guidelines. Results: Corticosteroids was used in 100% of cases. Most of cases with CNS infection who received steroid treatment guided by treatment protocol showed marked improvement in GCS score, tendon reflexes, muscle tone and convulsions.Conclusion: Corticosteroids are usually the primary drugs used to treat immune-mediated disorders of the CNS, including corticosteroid-responsive meningitis and corticosteroid-responsive meningomyelitis.

Growth Failure in a Series of Iranian Patients with Juvenile Idiopathic Arthritis

Background: Juvenile Idiopathic Arthritis (JIA) is accompanied by growth failure, mostly occurring due to chronic inflammation and use of corticosteroids for treatment. The aim of our study was to determine the prevalence of short stature in JIA patients and possible systemic disorders which may affect the growth pattern in this group of patients. Methods: In this cross-sectional study erformed from June 2014 to May 2015, JIA patients with a history of more than one-year treatment were examined by an endocrinologist and based on their height standard deviation score (SDS) two groups were determined: Group A > -2SD and group B < -2SD. Complete blood count, thyroid function tests and 25OHD3 level were assessed in both groups, but other laboratory tests, including liver and renal function tests, growth hormone stimulation test, urine analysis and culture, as well as left hand and wrist X-ray for bone age determination, were done in group B. Results: Of 117 JIA patients who were enrolled, 41 patients were under -2SD (19% of pauciarticular, 62% of poly articular and 33% of systemic onset). The mean height SDS in group B was -3.48 ± 1.28 (compared to -0.9 ± 0.8 in their parents). We found hypovitaminosis D in 73% of our patients. The prevalence of subclinical hypothyroidism was 7.4% (5% of group A and 9.7% of group B). Twenty-four percent (10 patients) of group B did not respond to growth hormone (GH) stimulation test and 14.6% of them (6 patients) were possibly GH resistant. Liver function tests and renal function tests were normal in all the patients. There was no difference between 2 groups in hypothyroidism and hypovitaminosis D but polyarticular type of the disease was associated with short stature (P Value < 0.000). Conclusions: Growth failure is common in JIA patients. So they, especially those with polyarticular type, need to be visited periodically by an endocrinologist.

HIV-associated opportunistic CNS infections: pathophysiology, diagnosis and treatment.

Nearly 30 years after the advent of antiretroviral therapy (ART), CNS opportunistic infections remain a major cause of morbidity and mortality in HIV-positive individuals. Unknown HIV-positive disease status, antiretroviral drug resistance, poor drug compliance, and recreational drug abuse are factors that continue to influence the morbidity and mortality of infections. The clinical and radiographic pattern of CNS opportunistic infections is unique in the setting of HIV infection: opportunistic infections in HIV-positive patients often have characteristic clinical and radiological presentations that can differ from the presentation of opportunistic infections in immunocompetent patients and are often sufficient to establish the diagnosis. ART in the setting of these opportunistic infections can lead to a paradoxical worsening caused by an immune reconstitution inflammatory syndrome (IRIS). In this Review, we discuss several of the most common CNS opportunistic infections: cerebral toxoplasmosis, progressive multifocal leukoencephalopathy (PML), tuberculous meningitis, cryptococcal meningitis and cytomegalovirus infection, with an emphasis on clinical pearls, pathological findings, MRI findings and treatment. Moreover, we discuss the risk factors, pathophysiology and management of IRIS. We also summarize the challenges that remain in management of CNS opportunistic infections, which includes the lack of phase II and III clinical trials, absence of antimicrobials for infections such as PML, and controversy regarding the use of corticosteroids for treatment of IRIS.

Use of Corticosteroids in a Population-Based Cohort of Boys With Duchenne and Becker Muscular Dystrophy

The use of corticosteroids for treatment of Duchenne and Becker muscular dystrophy in clinical practice from 1991 through 2005 was reviewed in a large population-based cohort (MD STARnet) of boys in 4 regional sites and 6 clinics of the United States. Corticosteroid use increased from 20% (11 of 56 individuals) in 1991 to 44% (93 of 218 individuals) in 2005. Average use varied by site and ranged from 15% to 49%. The median age of corticosteroid initiation was 6.9 years (range, 3.7-17.4 years). Dosage and growth information was available for 102 participants and showed a median dose as 0.729 mg/kg for prednisone and 0.831 mg/kg for deflazacort. T. The most common reasons that corticosteroids were discontinued included weight gain, behavioral side effects, and loss of ambulation, resulting in full-time wheelchair use. Substantial variations in clinical practice were identified among study sites.

Altered Pathogenesis of Porcine Respiratory Coronavirus in Pigs due to Immunosuppressive Effects of Dexamethasone: Implications for Corticosteroid Use in Treatment of Severe Acute Respiratory Syndrome Coronavirus

The pathogenesis and optimal treatments for severe acute respiratory syndrome (SARS) are unclear, although corticosteroids were used to reduce lung and systemic inflammation. Because the pulmonary pathology of porcine respiratory coronavirus (PRCV) in pigs resembles SARS, we used PRCV as a model to clarify the effects of the corticosteroid dexamethasone (DEX) on coronavirus (CoV)-induced pneumonia. Conventional weaned pigs (n = 130) in one of four groups (PRCV/phosphate-buffered saline [PBS] [n = 41], PRCV/DEX [n = 41], mock/PBS [n = 23], and mock/DEX [n = 25]) were inoculated intranasally and intratracheally with the ISU-1 strain of PRCV (1 x 10(7) PFU) or cell culture medium. DEX was administered (once daily, 2 mg/kg of body weight/day, intramuscularly) from postinoculation day (PID) 1 to 6. In PRCV/DEX pigs, significantly milder pneumonia, fewer PRCV-positive cells, and lower viral RNA titers were present in lungs early at PID 2; however, at PID 4, 10, and 21, severe bronchointerstitial pneumonia, significantly higher numbers of PRCV-positive cells, and higher viral RNA titers were observed compared to results for PRCV/PBS pigs. Significantly lower numbers of CD2(+), CD3(+), CD4(+), and CD8(+) T cells were also observed in lungs of PRCV/DEX pigs than in those of PRCV/PBS pigs at PID 8 and 10, coincident with fewer gamma interferon (IFN-gamma)-secreting cells in the tracheobronchial lymph nodes as determined by enzyme-linked immunospot assay. Our results confirm that DEX treatment alleviates PRCV pneumonia early (PID 2) in the infection but continued use through PID 6 exacerbates later stages of infection (PID 4, 10, and 21), possibly by decreasing cellular immune responses in the lungs (IFN-gamma-secreting T cells), thereby creating an environment for more-extensive viral replication. These data have potential implications for corticosteroid use with SARS-CoV patients and suggest a precaution against prolonged use based on their unproven efficacy in humans, including possible detrimental secondary effects.

Effective use of corticosteroids in treatment of plastic bronchitis with hemoptysis in Chinese adults

To investigate whether corticosteroids are effective in the treatment of plastic bronchitis with hemoptysis. A retrospective, clinical study was undertaken. Thirty two patients with only first episodes of plastic bronchitis with hemoptysis were divided into a steroid group (n=18) treated with glucocorticoids, and a non-steroid group (n=14). The supportive therapy was uniformly applied to both groups, except for glucocorticoids. Variables such as temperature and white blood cell counts were determined. Furthermore, the volume of hemoptysis and bronchial casts were evaluated in detail daily. There was no difference in the demographic data and variables at baseline between both groups (all P>0.05). On days 5, 6, 7 and 8, the volume of hemoptysis was significantly decreased in the steroid group compared with the non-steroid group (43+/-15 mL vs 117+/-33 mL on d 5, 29+/-12 mL vs 97+/-23 mL on d 6, 18+/-10 mL vs 80+/-20 mL on d 7, and 13+/-8 mL vs 66+/-14 mL on d 8; all P<0.05), and on d 10 after fibreoptic bronchoscopy, the cases with bronchial casts was reduced evidently in the steroid group in comparison with the non-steroid group (OR=5.69, 95% CI=1.76-43.6; P=0.005). There was no significance in mechanical ventilation and mortality between both groups. Despite some limitations of this study, it has been demonstrated that, on the basis of common supportive therapy, corticosteroids would be effective and safe for the treatment of plastic bronchitis with hemoptysis.

Use of Corticosteroids for Treatment of Interstitial Lung Disease

The use of corticosteroids for treatment of interstitial lung disease (ILD) is problematic because of significant side effects and limited efficacy in some ILDs, particularly idiopathic pulmonary fibrosis (IPF). This review summarizes recent data and controversies regarding corticosteroid therapy in IPF and sarcoidosis. A few trials, which have compared corticosteroids alone with corticosteroids in combination with immunosuppressives for patients with IPF, suggest that combination therapy is more effective and should be the first-line empiric therapy. Other anti-inflammatory agents such as colchicine do not appear to be more effective than corticosteroids but are better tolerated. Therapy with new antifibrotic agents such as pirfenidone and interferon appears promising; however, its efficacy needs to be established in well-designed, long-term studies with control populations. Although corticosteroids are highly effective in treating acute symptoms and functional deterioration in sarcoidosis, the long-term benefit of chronic corticosteroid use for patients who fail to remit is probably small. Alternative therapies, particularly methotrexate, have been used to suppress clinical deterioration in sarcoidosis. Although results in some studies are encouraging, the efficacy of methotrexate and/or an alternative regimen in the treatment of sarcoidosis remains to be established. Clin Pulm Med 2000;7(1):9-14

The Use of Corticosteroids for Treatment of Neurologic Disease

The Use of Corticosteroids for Treatment of Neurologic Disease