Prolonged Corticosteroid Treatment Research Articles

Bartonella henselae mitral valve endocarditis associated with multi‐resistant Enterococcus faecalis bacteraemia in a cat

AbstractFeline infective endocarditis is a difficult condition to detect and diagnose early, with a poor long‐term prognosis. This case report describes the clinical, laboratory, instrumental and histological findings in a 12‐year‐old cat with Bartonella henselae endocarditis associated with multi‐resistant Enterococcus faecalis bacteraemia. The latter pathogen recently emerged as deadly nosocomial bacteria in humans and is considered a common cause of infective endocarditis. The prolonged corticosteroid therapy administered in the cat probably played a role in the onset of B. henselae endocarditis and E. faecalis intestinal translocation and bacteraemia. Echocardiography remains the tool of choice to suspect infective endocarditis, as it can detect vegetative lesions consistent with this condition. Feline infective endocarditis should always be considered as a differential diagnosis in cats, especially when there are signs of systemic disease, a history of prolonged corticosteroid treatment or concomitant infections.

THE ASSOCIATION BETWEEN CORTICOSTEROID USE AND PROGNOSIS AND MORTALITY IN CHILDREN WITH SEPTIC SHOCK: A SYSTEMATIC REVIEW

Background/ objectives: The leading factor in pediatric death is septic shock. The use of corticosteroids, however, is still debatable. The management of septic shock has included the adjunct use of several corticosteroids and treatment plans. At the cellular and tissular levels, the various medications and their modes of administration differ qualitatively and quantitatively. This comprehensive analysis looked at the likelihood of mortality and prognosis for children with septic shock who were supplemented with corticosteroids. Methods: PubMed, Web of Science, Science Direct, and Google Scholarwere systematically searched to include the relevant literature. Rayyan QRCI was used throughout this systematic approach. Results/ Interpretation: The use of corticosteroids in pediatric septic shock patients is debatable. However, this study supports that corticosteroids are not recommended for children with septic shock. In order to increase generalizability and determine the ideal timing to begin treatment, the ideal dose of hydrocortisone (or an equivalent), and the duration and mode of withdrawal from treatment, additional studies are required to examine the role of prolonged low-dose corticosteroid treatment for septic shock in developing nations.

Prolonged oral corticosteroid treatment in patients with systemic lupus erythematosus: An evaluation of 12-month economic and clinical burden.

BACKGROUND: Prolonged, high-dose corticosteroid treatment for systemic lupus erythematosus (SLE) is associated with substantial health care costs, health care resource utilization (HCRU), and adverse events (AEs). OBJECTIVE: To compare all-cause health care costs, HCRU, and oral corticosteroid (OCS)-related AEs among patients with prevalent OCS use and patients without OCS use. METHODS: This retrospective, longitudinal cohort study (GSK study 214100) used claims data from the IQVIA Real-World Data Adjudicated Claims - US, IQVIA, Inc, database between January 1, 2006, and July 31, 2019, to identify patients with SLE. Patients with at least 1 OCS pharmacy claim during the study period and continuous OCS use during the 6-month pre-index (baseline) period (index date is the date of the first OCS claim following 6 months' continuous use) formed the "prevalent OCS use cohort." This cohort was subdivided based on the level of OCS exposure during the 12-month observation period, ie, the number of 6-month periods of greater than 5 mg/day OCS use (0, 1, or 2). Patients without OCS claims formed the "no OCS use cohort." All patients had continuous enrollment during the baseline and observation periods, had at least 1 inpatient or at least 2 outpatient SLE diagnosis codes during baseline, and were aged at least 5 years at index. A 2-part model, a generalized linear regression model with a negative binomial distribution, and a multivariate logistic regression model were used to compare health care costs, HCRU, and the odds of developing an OCS-related AE between cohorts, respectively. RESULTS: The no OCS use and prevalent OCS use cohorts included 21,517 and 16,209 patients, respectively. Adjusted health care cost differences (95% CI) were significantly lower for the no OCS use cohort vs all prevalent OCS use exposure categories ($5,439 [$4,537-$6,371] vs $17,856 [$16,368-$19,498]), driven by inpatient stays and outpatient visits; HCRU was also significantly lower (adjusted incidence rate ratios vs no OCS use cohort [95% CI]: 1.20 [1.16-1.23] vs 1.47 [1.41-1.52]). Health care costs and HCRU increased with increasing length of OCS exposure. OCS-related AEs occurred more frequently for all prevalent OCS use exposure categories vs the no OCS use cohort (odds ratio [95% CI]: 1.39 [1.25-1.55] vs 2.32 [2.02-2.68]), driven by hematologic/oncologic and immune system-related AEs. The mean (SD) average daily dose of OCS increased with increasing periods of prevalent OCS use (2.5 [1.3], 6.9 [31.1], and 34.6 [1,717.3] mg/day, respectively, for patients with 0, 1, and 2 periods of OCS use). CONCLUSIONS: Prevalent OCS use incurs a substantial clinical and economic burden, highlighting the need for restricted OCS doses and durations. DISCLOSURES: This study (GSK Study 214100) was funded by GSK. GSK was involved in designing the study, contributing to the collection, analysis, and interpretation of the data, supporting the authors in the development of the manuscript, and funding the medical writing assistance. All authors, including those employed by GSK, approved the content of the submitted manuscript and were involved in the decision to submit the manuscript for publication. Dr DerSarkissian, Dr Duh, and Mr Benson are employees of Analysis Group, which received research funding from GSK to conduct this study. Dr Wang, Ms Gu, and Mr Vu are former employees of Analysis Group. Mr Bell is an employee of GSK and holds stocks and shares in the company. Ms Averell and Dr Huang are former employees of GSK and held stocks and shares in the company at the time of the study.

Severe COVID-19 with persistent respiratory failure-A retrospective cohort study in a tertiary centre in Malaysia.

Management of severe COVID-19 patients with persistent respiratory failure after acute phase treatment is not only challenging, but evidence for treatment is scarce, despite some authors reporting favourable clinical responses to corticosteroid therapy in histologically proven secondary organising pneumonia (OP). This study aimed to report the course of the disease, radiological pattern and clinical outcomes of severe COVID-19 patients with persistent respiratory failure. This was a retrospective cohort study of severe COVID-19 patients who were admitted to a single tertiary centre from 1 January 2021 to 30 June 2021. The clinical data of the patients during admission and clinic follow-up, including radiological images, were traced using electronic medical records. In our cohort, the mortality rate for those with severe COVID-19 was 23.1% (173/749). Among the survivors, 46.2% (266/576) had persistent respiratory failure (PRF) after 14 days of illness. Of them, 70.3% (187/266) were followed up, and 68% (128/187) received oral corticosteroid (prednisolone) maintenance treatment. OP pattern made up the majority (81%) of the radiological pattern with a mean severity CT score of 10 (SD±3). The mean prednisolone dose was 0.68mg/kg/day with a mean treatment duration of 47 days (SD±18). About one-third of patients (67/187) had respiratory symptoms at 4 weeks (SD±3). Among 78.1% (146/187) who had a repeated CXR during follow-up, only 12 patients (8.2%, SD±3) had radiological improvement of less than 50% at 6 weeks (SD±3), with 2 of them later diagnosed as pulmonary tuberculosis. Functional assessments, such as the 6-minute walk test and the spirometry, were only performed in 52.4% and 15.5% of the patients, respectively. Almost half of the patients with severe COVID-19 had PRF, with a predominant radiological OP pattern. More than two-thirds of the PRF patients required prolonged oral corticosteroid treatment. Familiarising clinicians with the disease course, radiological patterns, and potential outcomes of this group of patients may better equip them to manage their patients.

Mesenteric Panniculitis, Sclerosing Mesenteritis and Mesenteric Lipodystrophy: Descriptive Review of a Rare Condition.

Mesenteric panniculitis (MP) is the preferred nomenclature for a continuum of inflammatory diseases of the mesentery. The diagnosis of MP is often based on the appearance of a mass-like structure at the root of the mesentery. Characteristic histology includes focal fat necrosis, chronic inflammation, and sometimes mesenteric fibrosis. At present, robust literature related to diagnosis and management of MP are limited. MP is postulated to be an immune-mediated chronic inflammatory and/or a paraneoplastic disease. A personal or family history of other autoimmune diseases is commonly apparent. Several inciting events have been identified that possibly act as triggers in the development of the disease. Trauma, abdominal surgery, infection, and various cancers have been associated with mesenteric panniculitis. There are several diagnostic and histologic criteria that aid in making the diagnosis of MP. The differential diagnosis for a mesenteric mass includes neoplastic disease, and a biopsy may be indicated to rule out other conditions. While cases of MP with a short duration of symptoms, or spontaneously regression may occur, some patients experience prolonged periods of pain, fever, and alterations in bowel habit, causing significant morbidity. A variety of medical therapies have been suggested for MP. Only two, thalidomide and low-dose naltrexone, have been prospectively evaluated. For patients with chronic MP, good responses to prolonged corticosteroid treatment have been reported. Novel therapies include thalidomide and low-dose naltrexone. Hormonal and immunomodulatory therapies are also used based on small case series, but these treatments may have significant side effects. Surgical intervention is not curative and is avoided except for relief of focal bowel obstruction secondary to fibrotic forms of the disease.

Persistent Aseptic Pyelonephritis After Acute Bacterial Pyelonephritis: Possible Role of Corticosteroids

Persistent Aseptic Pyelonephritis After Acute Bacterial Pyelonephritis: Possible Role of Corticosteroids

Emerging Cutaneous Phaeohyphomycosis Caused by Alternaria infectoria.

Alternaria species belong to a group of opportunistic fungi that causes skin infection mainly in immunosuppressed patients. The authors describe two clinically distinct cases of cutaneous alternariosis caused by Alternaria infectoria in patients under prolonged corticosteroid treatment. Additionally, a brief review of published cases in portuguese patients is conducted.

THE BENEFITS OF CORTICOSTEROIDS IN COVID-19 WITH ORGANIZING PNEUMONIA-LIKE PATTERN: A CLINICAL REPORT OF SUCCESSFUL TREATMENT

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Since the outbreak of COVID-19 (disease caused by severe acute respiratory syndrome coronavirus 2 - SARS-CoV-2), the world faces a major public health crisis.Organizing pneumonia (OP) is a relatively rare condition, that can be idiopathic or, more commonly, result from infections, drugs or autoimmunity (secondary OP) #1. Viral induced OP throughout the severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and H1N1 viral pandemics was well documented #2. The reported imaging findings of COVID-19 suggest that secondary OP may be occurring even more often #2. CASE PRESENTATION: 74-y-old man, evaluated in the emergency room for dry cough and asthenia with 1 week of evolution. He presented with hypoxemic respiratory failure (PaO2/FiO2 ratio: 276), and tested positive for SARS-CoV-2, being admitted in the COVID department. Treatment with Dexamethasone 6mg was started but a week later (day 14 of illness) there was a clinical deterioration, with worsening of the respiratory insufficiency (PaO2/FiO2 ratio: 175), requiring introduction of non-invasive mechanical ventilation with high oxygen rates. A clinical and gasometrical improvement (PaO2/FiO2 ratio: 230»253) was then observed with slow reduction and weaning from corticosteroids at D10 of dexamethasone. At day 20 of the disease, there was a new clinical and gasometrical worsening (PaO2/FiO2: 162), and it was decided to restart dexamethasone 6mg. No clinical improvement was observed in the following days and a chest computed tomography (CT) was performed, revealing multiple peripheral areas of consolidation and bilateral ground glass opacities, suggestive of an OP-like pattern. Given these findings, the case was discussed in a multidisciplinary team reunion, who considered the diagnosis of OP secondary to COVID-19 infection. It was decided to initiate 'pulse-dose' methylprednisolone 1000mg IV for 3 days and posteriorly the dosage of steroids was tapered every 3 days. There was an abrupt reduction in oxygen and ventilatory support needs and he was discharge requiring only 1L of oxygen and showing significant radiological improvement. After 3 months of follow-up, chest CT scan revealed dramatic improvements regarding previous findings. DISCUSSION: The definitive role of SARS-CoV-2 infection in diffuse lung injury is still unclear, but it is expected that it might induce host immune responses that damage the lungs. Corticosteroids, as immunosuppressive and anti-inflammatory agents, can reduce lung damage by regulating various inflammatory responses #3. CONCLUSIONS: This case suggests that corticosteroids may be an option to consider in COVID-19 pneumonia with an OP-like pattern. Secondary OP often requires prolonged corticosteroid treatment. It is important to increase recognition of this diagnosis, in order to start the appropriate treatment, which may lead to a reduction of the harmful consequences of COVID-19. REFERENCE #1: Drakopanagiotakis F, Paschalaki K, Abu-Hijleh M, Aswad B, Karagianidis N, Kastanakis E, Braman SS, Polychronopoulos V. Cryptogenic and secondary organizing pneumonia: clinical presentation, radiographic findings, treatment response, and prognosis. Chest. 2011 Apr;139(4):893-900. doi: 10.1378/chest.10-0883. Epub 2010 Aug 19. PMID: 20724743. REFERENCE #2: Kory P, Kanne JP. SARS-CoV-2 organising pneumonia: 'Has there been a widespread failure to identify and treat this prevalent condition in COVID-19?'. BMJ Open Resp Res 2020;7:e000724. doi:10.1136/ bmjresp-2020-000724 REFERENCE #3: Fauci AS. Mechanisms of the immunosuppressive and anti-inflammatory effects of glucocorticosteroids. J Immunopharmacol. 1978;1:1-25. DISCLOSURES: No relevant relationships by Mariana Argel, source=Web Response No relevant relationships by Joana Correia, source=Web Response No relevant relationships by Marta Sousa, source=Web Response No relevant relationships by Antonio Torres, source=Web Response

Characteristics of Immune Checkpoint Inhibitor-Induced Colitis: A Systematic Review.

Immune checkpoint inhibitors (ICIs) including anti-CTLA-4, anti-PD-1, and anti-PD-L1 antibodies have been increasingly used for various malignancies. These ICIs activate immune functions to treat malignant tumors; however, this causes characteristic complications called immune-related adverse events (irAE). In the gastrointestinal tract, ICIs cause adverse events such as diarrhea and enterocolitis, thus warranting treatment discontinuation. These irAEs require treatment that suppresses immunity; however, no treatment strategies based on approved guidelines have been reported. This review aimed to investigate the current treatment status for refractory cases of ICI-induced colitis in accordance with their diagnosis, therapy, and prognosis. We systematically reviewed studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) checklist. Two investigators searched PubMed and Scopus in January 2019. We extracted data, including the number of ICI-treated patients developing colitis and diarrhea. The number of cases classified as severe per the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) definitions and the progress of corticosteroid-treated and anti-TNF-α- antibody-treated cases (e.g., infliximab) were recorded. Details of further treatment were also recorded for cases that did not improve with antiTNF-α- antibody. Among patients receiving anti-CTLA-4 antibody, corticosteroids were administered to 14.6% of patients, and infliximab was administered to 5.7% of patients. Among patients receiving anti-PD-1/PD-L1 antibody, corticosteroids were administered to 2.37% of patients. For refractory cases unsuccessful with infliximab, the continuation of infliximab every 2 weeks, tacrolimus administration, prolonged corticosteroid treatment, colectomy, or vedolizumab administration were reported. Treatment of ICI-induced colitis is important to avoid the need to discontinue cancer treatment. Many therapeutic agents for inflammatory bowel disease are reportedly effective in treating refractory ICI-induced colitis.

Endogenous fungal endophthalmitis following intensive corticosteroid therapy in severe COVID-19 disease.

Purpose:To report endogenous fungal endophthalmitis, postrecovery from severe COVID-19 infection in otherwise immunocompetent individuals, treated with prolonged systemic steroids.Methods:Retrospective chart review of cases with confirmed and presumed fungal endogenous endophthalmitis, following severe COVID-19 disease, treated at two tertiary care referral eye institutes in North India.Results:Seven eyes of five cases of endogenous fungal endophthalmitis were studied. All cases had been hospitalized for severe COVID-19 pneumonia and had received systemic steroid therapy for an average duration of 42 ± 25.1 days (range 18–80 days). All the cases initially complained of floaters with blurred vision after an average of 6 days (range 1–14 days) following discharge from hospital. They had all been misdiagnosed as noninfectious uveitis by their primary ophthalmologists. All eyes underwent pars plana vitrectomy (PPV) with intravitreal antifungal therapy. Five of the seven eyes grew fungus as the causative organism (Candida sp. in four eyes, Aspergillus sp. in one eye). Postoperatively, all eyes showed control of the infection with a marked reduction in vitreous exudates and improvement in vision.Conclusion:Floaters and blurred vision developed in patients after they recovered from severe COVID-19 infection. They had received prolonged corticosteroid treatment for COVID-19 as well as for suspected noninfectious uveitis. We diagnosed and treated them for endogenous fungal endophthalmitis. All eyes showed anatomical and functional improvement after PPV with antifungal therapy. It is important for ophthalmologists and physicians to be aware of this as prompt treatment could control the infection and salvage vision.

Combination molecular therapies for type 1 spinal muscular atrophy.

Data on combining molecular therapies that increase survival motor neuron protein for spinal muscular atrophy type 1 (SMA1) is lacking. This was a retrospective study describing our centers' experiences in treating SMA1 patients with combination therapy. Five children received nusinersen and onasemnogene abeparvovec-xioi (onasemnogene). Four were receiving nusinersen prior to onasemnogene. Nusinersen was continued in three. Marked liver enzyme elevations resulted in prolonged corticosteroid treatment in two patients with hospitalization and liver biopsy in one; milder liver enzyme elevations were noted in the other two. One patient received onasemnogene first, and then nusinersen. No adverse effects were noted. All patients improved. Combination molecular therapy is tolerated in SMA1 patients. Further studies are needed to determine whether there are circumstances in which combination therapy would be more efficacious than either monotherapy. Prolonged corticosteroid use and liver toxicity monitoring may be necessary with onasemnogene therapy.

Rationale for Prolonged Corticosteroid Treatment in the Acute Respiratory Distress Syndrome Caused by Coronavirus Disease 2019.

Rationale for Prolonged Corticosteroid Treatment in the Acute Respiratory Distress Syndrome Caused by Coronavirus Disease 2019.

The Treatment Algorithm for Meibomyitis, Hordeolum and Halazion

Despite the fact that the frequency of treatment the eyelids inflammatory diseases affecting the modified sebaceous glands (Meibomian glands, Zeiss glands) is very high in outpatient clinical practice, and the basic principles of treating this pathology are well known to everyone, there are always many questions. Therefore, interdisciplinary approach with gastroenterologists, dermatologists, endocrinologists and other specialists is often required treatment of this patients group. In addition, the transition of the inflammatory process to a chronic form and the encapsulation of the inflammatory focus and / or the formation of a halazion requires an accurate algorithm of actions from the practitioner, which depends on the duration of the pathological process. There is always a question — what form of an antibacterial drug is better to prescribe — ointment or drops? In addition, there is no consensus on the use of hormone therapy in the treatment of meibomyitis, hordeolum and chalazion. This article presents an algorithm for the prevention and treatment of this group of patients, which involves a certain sequence of therapeutic and preventive measures, depending on the severity and duration of the inflammatory process. Eyelid hygiene (warm compresses + self-massage of the eyelids with gel) is recommended in case of chronic blepharitis clinical signs, complaints of dryness, discomfort, wearing contact lenses. In case of the acute inflammatory process — meibomyitis and/or hordeolum in addition to eyelid hygiene, local antibiotic therapy is recommended. If a halazion is forming the choice of treatment tactics (local instillation therapy, intracapsular administration of a prolonged corticosteroid or surgical treatment) depends on the halazion duration (more or less than 2 months). The presented algorithm has the practical importance, since adequate treatment will not only eliminate the focus of chronic infection on the eyelids, but also improve the patient’s quality of life, since the presence of such a disease gives pronounced psycho-emotional discomfort because of its localization zone.

Potential Anti-Thrombotic Effect without Accompanying Hemorrhage with Fostamatinib Use in Patients with Immune Thrombocytopenia

Potential Anti-Thrombotic Effect without Accompanying Hemorrhage with Fostamatinib Use in Patients with Immune Thrombocytopenia

Favorable survival in lung transplant recipients on preoperative low-dose, as compared to high-dose corticosteroids, after hematopoietic stem cell transplantation.

Although the number of patients developing pulmonary complications after hematopoietic stem cell transplantation (HSCT) necessitating lung transplantation (LT) is increasing, a little information is available about factors influencing the prognosis after LT in these patients. Corticosteroids represent the first-line therapy for pulmonary complications after HSCT; however, prolonged corticosteroid treatment prior to LT increases the potential risks of LT. In this study, we assessed the effect of preoperative corticosteroid therapy on long-term survival in patients undergoing LT after HSCT. We retrospectively investigated data from 13 patients who had received high-dose corticosteroid therapy and nine who had received low-dose corticosteroid therapy prior to LT for pulmonary complications after HSCT. Other than the preoperative corticosteroid dose, patient clinical characteristics did not differ. The incidence of postoperative complications within the first year after LT was significantly lower in the low-dose corticosteroid group (p=0.026). Survival after LT was also significantly better in the low-dose corticosteroid group than in the high-dose corticosteroid group (p=0.034). In recipients of LT after HSCT, preoperative low-dose corticosteroid use, as compared to preoperative high-dose corticosteroid use, could limit the risks of postoperative complications developing within the first year after the LT, leading to improved long-term survival after LT.

A novel anti-IL4Rα nanoparticle efficiently controls lung inflammation during asthma.

Drug resistance and the harmful side effects accompanying the prolonged corticosteroid treatment of chronic pulmonary diseases prompted the development of more specific anti-inflammatory approaches. Several strategies aiming to block IL4Rα, the receptor for a key pro-inflammatory pathway, were investigated. However, their efficiency was limited, mostly due to the systemic or subcutaneous route of administrations. In this paper, we examined the ability of an intranasal treatment with biocompatible nanoparticles targeting IL4Rα to control lung inflammation in ovalbumin (OVA)-sensitized mice. OVA-sensitized mice were treated with anti-IL4Rα-conjugated nanoparticles. The levels of pro-inflammatory cytokines in the lungs and broncho-alveolar lavage fluid (BALF) were determined using a cytokine array assay. The effects of nanoparticle treatment on the activation of lung inflammatory cells and their ability to proliferate and produce cytokines were determined using fluorescence-activated cell sorting (FACS) analysis. Lung inflammation was also monitored using immunohistochemical staining. Treatment with the anti-IL4Rα nanoparticles significantly decreased pro-inflammatory cytokine expression and release in BALF and airway lung tissue in mice. The numbers of lung tissue lymphocytes, neutrophils and eosinophils were also decreased. Interestingly, anti-IL4Rα nanoparticles deactivated CD4 and CD8 T cells in lung tissue and inhibited their ability to produce pro-inflammatory cytokines to a significantly lower level than the treatment with free anti-IL4Rα. Moreover, they induced a sustained low level of lung inflammation for 1 week following the last instillation compared with the treatment with free anti-IL4Rα antibodies. Together, this data suggested that the enhanced tissue penetrability and sustainability of these nanoparticles improved the strength and durability of the immunosuppressive effects of anti-IL4Rα.

Atraumatic Femoral Head Necrosis in Adults.

Atraumatic necrosis of the femoral head is a common cause of hip arthrosis in middle age. In Germany, it affects 5000-7000 patients per year, corresponding to an incidence of 0.01%. Though rarer than primary hip arthrosis, it is still of major clinical and socio-economic significance. Patients with this problem should be diagnosed early and given stage-appropriate treatment. This review is based on pertinent publications that were retrieved by a selective search in the PubMed, Embase, Medline, and Cochrane Library databases using the terms "osteonecrosis," "femoral head necrosis," "diagnosis," "classification," "conservative treatment," "surgical treatment," "joint preservation," "osteotomy," and "arthroplasty," as well as a recent guideline on atraumatic necrosis of the femoral head in adults. The etiology and pathogenesis of atraumatic femoral head necrosis in adults are not yet fully clear. The main risk factor is prolonged corticosteroid treatment. Nonspecific complaints and an initially normal plain x-ray of the hip can delay the diagnosis. The diagnosis is established by plain x-ray, computerized tomography, magnetic resonance tomography, and scintigraphy. Conservative treatment alone is not considered adequate. The range of surgical treatments includes joint-preserving and (for more severe necrosis) joint-resecting methods. Atraumatic femoral head necrosis in adults is a disease that progresses in stages; depending on its stage, it can either be cured or lead to hip arthrosis. A full cure is possible only in early stages. Current research focuses on the effect of new drugs on the intermediateand long-term outcome.

Methylprednisolone Protects Cardiac Pumping Mechanics from Deteriorating in Lipopolysaccharide-Treated Rats.

It has been shown that a prolonged low-dose corticosteroid treatment attenuates the severity of inflammation and the intensity and duration of organ system failure. In the present study, we determined whether low-dose methylprednisolone (a synthetic glucocorticoid) can protect male Wistar rats against cardiac pumping defects caused by lipopolysaccharide-induced chronic inflammation. For the induction of chronic inflammation, a slow-release ALZET osmotic pump was subcutaneously implanted to infuse lipopolysaccharide (1 mg kg−1 d−1) for 2 weeks. The lipopolysaccharide-challenged rats were treated on a daily basis with intraperitoneal injection of methylprednisolone (5 mg kg−1 d−1) for 2 weeks. Under conditions of anesthesia and open chest, we recorded left ventricular (LV) pressure and ascending aortic flow signals to calculate the maximal systolic elastance (Emax) and the theoretical maximum flow (Qmax), using the elastance-resistance model. Physically, Emax reflects the contractility of the myocardium as an intact heart, whereas Qmax has an inverse relationship with the LV internal resistance. Compared with the sham rats, the cardiodynamic condition was characterized by a decline in Emax associated with the increased Qmax in the lipopolysaccharide-treated rats. Methylprednisolone therapy increased Emax, which suggests that the drug may have protected the contractile status from deteriorating in the inflamed heart. By contrast, methylprednisolone therapy considerably reduced Qmax, indicating that the drug may have normalized the LV internal resistance. In parallel, the benefits of methylprednisolone on the LV systolic pumping mechanics were associated with the reduced cardiac levels of negative inotropic molecules such as peroxynitrite, malondialdehyde, and high-mobility group box 1 protein. Based on these data, we suggested that low-dose methylprednisolone might prevent lipopolysaccharide-induced decline in cardiac intrinsic contractility and LV internal resistance, possibly through its ability to reduce the aforementioned myocardial depressant substances. However, since our results were obtained in anesthetized open-chest rats, extrapolation to what may occur in conscious intact animals should be done with caution.

Vernal keratoconjunctivitis

Vernal keratoconjunctivitis (VKC) is a bilateral, usually seasonally recurrent inflammation of the conjunctiva. Clinically characteristic findings are tarsal giant conjunctival papillae (> 1mm) and/or limbal gelatinous changes (Trantas dots). The underlying etiology and pathophysiology of VKC remains unclear; however, clinical findings and immunohistochemical studies suggest a complex, both IgE-dependent and IgE-independent immune-mediated etiology. Several predisposing conditions include endocrine, genetic, neurogenic, environmental and socioeconomic risk factors. Mast cell stabilizers, antihistamines and topical corticosteroids are often used during acute flare-ups in VKC; however this approach is unsatisfactory for controlling severe cases and avoiding recurrences. Immunomodulatory agents, such as cyclosporin A and tacrolimus are promising alternative agents for long-term management. In most children the clinical course of VKC is self-limiting and may disappear following puberty; however, some VKC patients will face sight-threatening complications which are mainly due to corneal involvement and iatrogenic damage caused by prolonged corticosteroid treatment.

Predictors of Response to Corticosteroid Treatment in Patients with Early Acute Respiratory Distress Syndrome: Results of a Pilot Study

Prospective observational cohort study was performed to evaluate predictors for responsiveness to corticosteroid treatment in patients with acute respiratory distress syndrome (ARDS). Over the study period, a total of 20 patients (male 70%, median age 69) with ARDS were treated with corticosteroid within 72 h after intubation. The median lung injury score (LIS) and partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratios (PF ratios) were 3.0 (interquartile range, 2.7-3.0) and 146.6 (119.9-179.4), respectively. The median levels of triggering receptor expressed on myeloid cells (TREM-1) and procollagen peptide type III in bronchoalveolar lavage (BAL) fluid were 349.3 (225.6-634.9) pg/mL and 19.6 (11.7-39.7) pg/mL, respectively. After 7 days of corticosteroid treatment, 10 (50%) patients showed response to the treatment (successful extubation in 7 and 1-point or more reduction in LIS in 3). Compared to non-responders, responders had higher initial PF ratios (170.5 vs. 127.2, p=0.023), lower level of TREM-1 in BAL fluid (313.6 pg/mL vs. 520.5 pg/mL, p=0.029), and greater reduction in LIS at 3 days (-1 vs. 0, p<0.001). In conclusion, PF ratios and TREM-1 level in BAL fluid at baseline, and reduction in LIS at day 3 after the treatment were associated with the response to prolonged corticosteroid treatment (ClinicalTrials.gov Identifier: NCT01093287).