Changes in bone turnover markers after discontinuing long-term glucocorticoid administration in children with idiopathic nephrotic syndrome: a multicenter retrospective observational study.

BACKGROUND: Glucocorticoids affect bone turnover. Little is known about how bone turnover changes when glucocorticoids are discontinued following long-term administration. METHODS: This retrospective observational study was conducted on the relationship between discontinuation of long-term administration of glucocorticoid and bone turnover markers (BTMs) in patients with childhood-onset idiopathic nephrotic syndrome. Serum bone alkaline phosphatase (BAP), intact procollagen type 1 N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase-5b (TRACP-5b) were evaluated as BTMs. RESULTS: Thirty-eight pairs of BTMs at glucocorticoid administration and after discontinuation were analyzed in 29 patients. The median age at baseline was 12.4 (interquartile range, 9.0-14.5) years, and the median time from the onset of nephrotic syndrome was 5.9 (3.3-9.7) years. The mean period from prednisolone discontinuation to the measurement of BTMs after glucocorticoid discontinuation was 3.5 ± 1.0 months. Changes in BTMs after glucocorticoid discontinuation were modest when the daily prednisolone dose was < 0.25 mg/kg/day (ln BAP standard deviation [SD] score, p = 0.19; log intact P1NP SD score, p = 0.70; TRACP-5b, p = 0.95). When the daily prednisolone dose was ≥ 0.25 mg/kg/day, all BTMs increased significantly after glucocorticoid discontinuation (ln BAP SD score, p < 0.01; log intact P1NP SD score, p < 0.01; TRACP-5b, p < 0.01). CONCLUSIONS: Decreased BTMs can rise within a few months of discontinuing long-term glucocorticoid administration. When the administered glucocorticoid dose is low, changes in BTMs may be small. A higher resolution version of the Graphical abstract is available as Supplementary information.

[A Case of Unilateral Interstitial Lung Disease in a Patient Treated with Oxaliplatin, 5-Fluorouracil, and Leucovorin].

Respiratory symptoms are rarely reported as side effects of oxaliplatin, 5-fluorouracil, and Leucovorin(FOLFOX)therapy. We report a case of a patient with FOLFOX-induced unilateral interstitial pneumonia. The patient was a 68-year-old man who underwent ileocecal resection of cecum cancer. FOLFOX regimen was started as an adjuvant chemotherapy. After the administration of 11 courses, he visited our hospital with fever, dyspnea, and anorexia. We diagnosed this as FOLFOX- induced unilateral interstitial pneumonia through a blood test, chest radiograph, computed tomography, and bronchoscopy. Treatment was started with 30 mg of prednisolone, and the dosage was gradually decreased. The patient responded well to the treatment and was discharged from the hospital without any complications on the 33th day after admission.

A multicenter, open-label, uncontrolled, single-arm phase 2 study of tirabrutinib, an oral Bruton's tyrosine kinase inhibitor, in pemphigus.

BACKGROUND: The treatment of pemphigus is based on systemic corticosteroid use and adjuvant therapies, but some patients are resistant to conventional therapy. Tirabrutinib is a highly selective oral Bruton's tyrosine kinase inhibitor that may be clinically effective in treating pemphigus by suppressing B-cell signaling. OBJECTIVE: We investigated the efficacy and safety of tirabrutinib in patients with refractory pemphigus. METHODS: This was a multicenter, open-label, single-arm phase 2 study of Japanese patients with refractory pemphigus receiving appropriate treatment with an oral corticosteroid and adjuvant therapies. Patients received postprandial oral tirabrutinib 80 mg once daily for 52 weeks. After 16 weeks of tirabrutinib treatment, the corticosteroid dose was tapered to ≤10 mg/day of prednisolone equivalent. RESULTS: In total, 16 patients were evaluated (mean age, 52.5 years; 50 % male). The complete remission rate after 24 weeks of treatment (primary endpoint) was 18.8 % (3/16; 95 % confidence interval, 6.6 %-43.0 %). By Week 52, eight patients (50.0 %) achieved complete remission and 10 patients (62.5 %) achieved remission. Over 52 weeks of treatment, the mean prednisolone dose decreased from 17.03 to 7.65 mg/day. Incidences of adverse events (AEs) and adverse drug reactions were 87.5 % and 43.8 %, respectively. A relationship with tirabrutinib was ruled out for all serious AEs and Grade ≥3 AEs. CONCLUSION: Treatment with tirabrutinib enabled remission and reduced oral corticosteroid exposure over time and did not result in any major safety concerns in patients with refractory pemphigus. Thus, oral tirabrutinib may be a new treatment option for patients with refractory pemphigus.

Long-term effects on bone mineral density after four years of treatment with two intensive combination strategies, including initially high-dose prednisolone, in early rheumatoid arthritis patients: the COBRA-light trial.

In this study, no difference in bone loss was observed between patients with early RA initially treated with COmbinatietherapie Bij Reumatoide Artritis (COBRA) (including initially 60 mg/day prednisolone) and patients treated with COBRA-light (including initially 30 mg/day prednisolone) during 4-year observation. PURPOSE: To assess changes in bone mineral density (BMD) after 4 years in early rheumatoid arthritis (RA) patients initially treated with COBRA-light or COBRA therapy. METHODS: In a 1 year, open-label, randomised, non-inferiority trial, patients were assigned to COBRA-light (methotrexate 25 mg/week plus initially prednisolone 30 mg/day) or COBRA (methotrexate 7.5 mg/week, sulfasalazine 2 g/day plus initially prednisolone 60 mg/day) therapy. After 1 year, antirheumatic treatment was at the discretion of treating rheumatologists. BMD was measured at baseline and after 1, 2 and 4 years at hips and lumbar spine with dual-energy X-ray absorptiometry. BMD changes between treatment strategies on average over time were compared with GEE analysis. RESULTS: Data from 155 out of 162 patients could be analysed: 68% were female with a mean age of 52 (SD 13) years. Both COBRA-light and COBRA therapy showed declines in BMD at the total hip of -3.3% and -1.7%, respectively (p = 0.12), and the femoral neck, -3.7% and -3.0%, respectively (p = 0.95). At the lumbar spine, both treatment groups showed minor decline in BMD over 4 years: -0.5% and -1.0%, respectively (p = 0.10). CONCLUSION: In a treat-to-target design in early RA, over 4 years, no differences between groups were found in change in BMD at total hip, femoral neck and the lumbar spine. At the hip, bone loss was around 3% in both groups, while mild bone loss was observed at lumbar spine, both in patients starting prednisolone 60 and 30 mg/day. These data suggest that the well-known negative effects of prednisolone can be modulated by modern treatment of RA.

Stage-specific response in early mouse embryos exposed to prednisolone in vitro.

Corticosteroids are increasingly being used during the peri-implantation period to treat women with repeated IVF failure and recurrent miscarriage. However, the direct effects of prednisolone (PRDL), one of the commonly used corticosteroids on early embryo development is not understood. To mimic the possible clinical scenario and to understand the embryonic response to direct PRDL exposure, this pilot study was conducted in a mouse model. Cleavage stage embryos exposed to 3 and 30 µM PRDL in vitro were assessed for peri-implantation developmental potential, genetic integrity, inner cell mass (ICM) proliferation and pluripotency markers in the proliferated ICM cells. Exposure to 30 µM PRDL delayed the embryonic progression beyond compaction (P < 0.05) in comparison to vehicle control and, had reduced total cell number (P < 0.001) than all other groups. In addition, 30 µM PRDL exposure resulted in poor hatching potential (P < 0.05) and increased apoptosis in blastocysts (P < 0.05) compared to 3 µM PRDL. On the other hand, completely formed ICM outgrowths were significantly higher (P < 0.05) in 3 µM PRDL compared to control. However, no significant differences were observed in the expression of pluripotency genes. In conclusion, the trend observed in embryos exposed to PRDL in vitro provides important information concerning the use of this drug when treating patients at the peri-implantation phase of IVF cycles. However, the clinical value of this observation on human embryo development needs further research.

Prophylactic prednisolone for the prevention of early and intermediate adverse effects of radioactive iodine therapy in patients with thyroid cancer: study protocol for a single-centre, phase II/III, randomized, double-blinded, placebo-controlled clinical trial.

BACKGROUND: Radioactive iodine (RAI) therapy is the standard adjuvant treatment for differentiated thyroid cancer (i.e. papillary and follicular). RAI is associated with troublesome early, intermediate and late adverse effects. Although glucocorticoids are used for the management of these adverse effects, there is little evidence regarding the effectiveness of prophylactic glucocorticoids to prevent these complications. This trial will evaluate the efficacy of a short course of prophylactic glucocorticoids in the prevention of adverse effects of RAI treatment in patients with differentiated thyroid cancer. METHODS: A phase II/III, single-centre, randomized, double-blinded, placebo-controlled, parallel-arm clinical trial will be conducted. Patients with differentiated thyroid cancer who are referred to RAI therapy at the National Cancer Institute, Sri Lanka, will be randomized into two arms consisting of 200 patients each. The experimental group will receive prophylactic oral prednisolone 0.5 mg/kg and omeprazole 20 mg single dose 6 h before RAI therapy followed by oral prednisolone 0.5 mg/kg and omeprazole 20 mg daily for 3 days. The control group will receive oral placebo and omeprazole 20 mg single dose 6 h before RAI therapy followed by oral placebo and omeprazole 20 mg daily for 3 days. Clinically significant adverse effects assessed as related to RAI as well as prednisolone therapy and the quality of life parameters will be compared between the two groups. DISCUSSION: If proven beneficial, this intervention can be incorporated into the standard practice to reduce early and intermediate adverse effects of RAI for thyroid cancer with a potential improvement of quality of life. TRIAL REGISTRATION: Sri Lanka Clinical Trials Registry SLCTR/2020/009 . Registered prospectively on 23 February 2020. Items of the WHO Trial Registration Data Set are provided in the supplementary file.

Total remission of Tolosa-Hunt Syndrome with single-dose of infliximab / Remissão total da Síndrome de Tolosa-Hunt com dose única de infliximabe

Abstract Tolosa-Hunt syndrome is a painful ophthalmoplegia caused by non-specific granulomatous inflammation, corticoid-sensitive, of the cavernous sinus. The etiology is unknown. Recurrences are common. The diagnosis is made by exclusion, and a variety of other diseases involving the orbital apex, superior orbital fissure and cavernous sinus should be ruled out. This study reports a case of a 29-year-old woman, diagnosed with Tolosa-Hunt Syndrome, who presented ophthalmoparesis and orbital pain. She had poor response to corticotherapy and developed colateral effects, so she was treated with single infliximab dose immunosuppression, evolving total remission of the disease.

Resumo A Síndrome de Tolosa-Hunt é uma oftalmoplegia dolorosa causada por uma inflamação granulomatosa não específica, sensível a corticoides, do seio cavernoso. A etiologia é desconhecida. Recorrências são comuns. O diagnóstico é feito por exclusão, devendo ser descartada uma variedade de outras doenças que envolvem o ápice orbitário, fissura orbitária superior e seio cavernoso. O presente estudo trata-se de um relato de caso de uma paciente de 29 anos, diagnosticada com Síndrome de Tolosa-Hunt, que apresentou paresia e dor em região orbital. Obteve resposta pouco efetiva a corticoterapia e desenvolveu efeitos colaterais, por isso foi tratada com dose única de infliximabe, evoluindo com remissão total da doença.

Acetabular avascular necrosis following high-dose steroid treatment and chemotherapy for leukemia : Computer tomography analysis of treatment with impaction bone grafting.

Avascular necrosis (AVN) of the bone is thought to be a serious complication of treatment for acute lymphoblastic leukemia (ALL). The acetabulum is an unusual area to be affected by AVN, and there are currently no reports of successful joint salvage procedures found in the literature. We present a case of a 20-year-old man with ALL who was diagnosed with debilitating AVN of both acetabula 2 years following initial diagnosis of ALL and treatment with a multi-agent chemotherapy regimen including high-dose corticosteroids. After unsuccessful treatment with bisphosphonate therapy, the acetabular AVN underwent bilateral curettage and impaction bone grafting to prevent collapse of subchondral fractures with the hope of salvaging both hip joints. Computer tomography (CT) of the AVN affected areas, pre- and post-bone impaction grafting, demonstrated healing of the subchondral fractures and a doubling of bone density that was maintained at 2 years after surgery. The patient resumed full weight-bearing at 3 months after first surgery, continues to ambulate unrestricted, and remains pain free 3 years post-surgery.

Myocardial calcification in a patient with B-lymphoblastic leukemia accompanied by tumor lysis syndrome.

Myocardial calcification, a rare disease that leads to chronic or acute heart failure and with a poor prognosis, occurs in patients with abnormal calcium-phosphorus metabolism. The association between myocardial calcification and tumor lysis syndrome has not been reported to date. A 50-year-old man with hyperthermia and general malaise presented to our hospital and was clinically diagnosed with B-lymphoblastic leukemia (B-ALL) and febrile neutropenia accompanied by septic shock. Prednisolone was administered for tumor reduction. Two to three hours later, electrocardiography demonstrated ST elevation in V4-6, and blood tests showed elevated levels of cardiac enzymes. Transthoracic echocardiogram revealed diffuse severe hypokinesis with decreased left ventricular ejection fraction. Additionally, blood tests showed that serum phosphorus level increased to 8.0 mg/dl, which was likely due to tumor lysis syndrome. Circulatory and respiratory failure due to left heart failure progressed, and he died 3 days after administration of prednisolone. Pathological autopsy revealed diffuse proliferation of atypical B-lymphoblasts in the bone marrow, which led to the pathological diagnosis of B-ALL, accompanied by necrosis. On the cut surface of the heart, the left ventricle was dilated, and patchy yellowish-brown areas were present in the epicardial-side of the myocardium and spread through the circumferential wall of the left ventricle and interventricular septum. Microscopically, myocardial fibers were granularly basophilic in that area and were revealed as calcium deposits by Von Kossa staining. He was diagnosed with myocardial calcification. The drastic increase in the serum phosphorus level caused by tumor lysis syndrome seemed to be associated with myocardial calcification.

Long term tapering versus standard prednisolone treatment for first episode of childhood nephrotic syndrome: phase III randomised controlled trial and economic evaluation.

OBJECTIVE: To determine whether extending initial prednisolone treatment from eight to 16 weeks in children with idiopathic steroid sensitive nephrotic syndrome improves the pattern of disease relapse. DESIGN: Double blind, parallel group, phase III randomised placebo controlled trial, including a cost effectiveness analysis. SETTING: 125 UK National Health Service district general hospitals and tertiary paediatric nephrology centres. PARTICIPANTS: 237 children aged 1-14 years with a first episode of steroid sensitive nephrotic syndrome. INTERVENTIONS: Children were randomised to receive an extended 16 week course of prednisolone (total dose 3150 mg/m2) or a standard eight week course of prednisolone (total dose 2240 mg/m2). The drug was supplied as 5 mg tablets alongside matching placebo so that participants in both groups received the same number of tablets at any time point in the study. A minimisation algorithm ensured balanced treatment allocation by ethnicity (South Asian, white, or other) and age (5 years or less, 6 years or more). MAIN OUTCOME MEASURES: The primary outcome measure was time to first relapse over a minimum follow-up of 24 months. Secondary outcome measures were relapse rate, incidence of frequently relapsing nephrotic syndrome and steroid dependent nephrotic syndrome, use of alternative immunosuppressive treatment, rates of adverse events, behavioural change using the Achenbach child behaviour checklist, quality adjusted life years, and cost effectiveness from a healthcare perspective. Analysis was by intention to treat. RESULTS: No significant difference was found in time to first relapse (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17, log rank P=0.28) or in the incidence of frequently relapsing nephrotic syndrome (extended course 60/114 (53%) v standard course 55/109 (50%), P=0.75), steroid dependent nephrotic syndrome (48/114 (42%) v 48/109 (44%), P=0.77), or requirement for alternative immunosuppressive treatment (62/114 (54%) v 61/109 (56%), P=0.81). Total prednisolone dose after completion of the trial drug was 6674 mg for the extended course versus 5475 mg for the standard course (P=0.07). There were no statistically significant differences in serious adverse event rates (extended course 19/114 (17%) v standard course 27/109 (25%), P=0.13) or adverse event rates, with the exception of behaviour, which was poorer in the standard course group. Scores on the Achenbach child behaviour checklist did not, however, differ. Extended course treatment was associated with a mean increase in generic quality of life (0.0162 additional quality adjusted life years, 95% confidence interval -0.005 to 0.037) and cost savings (difference -£1673 ($2160; €1930), 95% confidence interval -£3455 to £109). CONCLUSIONS: Clinical outcomes did not improve when the initial course of prednisolone treatment was extended from eight to 16 weeks in UK children with steroid sensitive nephrotic syndrome. However, evidence was found of a short term health economic benefit through reduced resource use and increased quality of life. TRIAL REGISTRATION: ISRCTN16645249; EudraCT 2010-022489-29.

Twenty-four hour urinary cortisol excretion and the metabolic syndrome in prednisolone-treated renal transplant recipients.

Chronic prednisolone treatment in renal transplant recipients (RTR) causes metabolic abnormalities, which cluster in the metabolic syndrome (MS). It also suppresses the hypothalamic-pituitaryadrenal (HPA)-axis. We investigated whether HPA-axis suppression, as measured by 24h urinary cortisol excretion, is associated with presence of the MS and its individual components, in outpatient RTR with a functioning graft for >1year. Urinary cortisol was measured in 24h urine, using LC-MS/MS (LOQ 0.30nmol/L). We included 563 RTR (age 51±12years; 54% male) at median 6.0 [IQR, 2.6-11.5] years post-transplantation. MS was present in 439/563 RTR (78%). Median 24h urinary cortisol excretion was 2.0 [IQR, 0.9-5.1]nmol/24h. Twenty-four hour urinary cortisol excretion was independently associated with MS presence (OR=0.80 [95% CI, 0.66-0.98], P=0.02). It was also independently associated with bodyweight (st.ß=-0.11, P=0.007), waist circumference (st.ß=-0.10, P=0.01), BMI (st.ß=-0.14, P=0.001), fasting triglycerides (st.ß=-0.15, P=0.001), diabetes (st.ß=-0.12, P=0.005), and number of antihypertensives used (st.ß=-0.13, P=0.003). Suppressed HPA-axis activity, as reflected by decreased 24h urinary cortisol excretion, is associated with higher prevalence of MS and its individual components (i.e. central obesity, dyslipidemia, diabetes, hypertension) in prednisolone-treated RTR. Assessment of 24h urinary cortisol excretion by LC-MS/MS may be a tool to monitor metabolic side-effects of prednisolone in RTR.

Therapies for crohn's disease: a clinical update / Terapia farmacológica em portadores de doença de Crohn. Atualização clínica

ABSTRACT The main objectives of clinical therapy in Crohn's disease are clinical and endoscopic remission without the use of corticosteroids for long periods of time, prevention of hospitalization and surgery, and improvement of quality of life. The main limitation of drug therapy is the loss of response over the long term, which makes incorporation of new drugs to the therapeutic arsenal necessary. This review analyses the main drugs currently used in clinical treatment of Crohn's disease.

RESUMO Os principais objetivos da terapia clínica na doença de Crohn são a remissão clínica e endoscópica por tempo prolongado, sem o uso de corticosteroides, além de evitar hospitalizações e cirurgias, e melhorar a qualidade de vida. A principal limitação da terapêutica medicamentosa é a perda de reposta a longo prazo, o que faz com que a incorporação de novas drogas ao arsenal terapêutico seja necessária. Esta revisão aborda os principais medicamentos utilizados atualmente no tratamento clínico da doença de Crohn.

THERAPIES FOR CROHN'S DISEASE: a clinical update.

The main objectives of clinical therapy in Crohn's disease are clinical and endoscopic remission without the use of corticosteroids for long periods of time, prevention of hospitalization and surgery, and improvement of quality of life. The main limitation of drug therapy is the loss of response over the long term, which makes incorporation of new drugs to the therapeutic arsenal necessary. This review analyses the main drugs currently used in clinical treatment of Crohn's disease.

Interventions for treating hyperemesis gravidarum.

BACKGROUND: Hyperemesis gravidarum is a severe form of nausea and vomiting in pregnancy affecting 0.3% to 1.0% of pregnancies, and is one of the most common indications for hospitalization during pregnancy. While a previous Cochrane review examined interventions for nausea and vomiting in pregnancy, there has not yet been a review examining the interventions for the more severe condition of hyperemesis gravidarum. OBJECTIVES: To assess the effectiveness and safety, of all interventions for hyperemesis gravidarum in pregnancy up to 20 weeks' gestation. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and the Cochrane Complementary Medicine Field's Trials Register (20 December 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomized controlled trials of any intervention for hyperemesis gravidarum. Quasi-randomized trials and trials using a cross-over design were not eligible for inclusion.We excluded trials on nausea and vomiting of pregnancy that were not specifically studying the more severe condition of hyperemesis gravidarum. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed the eligibility of trials, extracted data and evaluated the risk of bias. Data were checked for accuracy. MAIN RESULTS: Twenty-five trials (involving 2052 women) met the inclusion criteria but the majority of 18 different comparisons described in the review include data from single studies with small numbers of participants. The comparisons covered a range of interventions including acupressure/acupuncture, outpatient care, intravenous fluids, and various pharmaceutical interventions. The methodological quality of included studies was mixed. For selected important comparisons and outcomes, we graded the quality of the evidence and created 'Summary of findings' tables. For most outcomes the evidence was graded as low or very low quality mainly due to the imprecision of effect estimates. Comparisons included in the 'Summary of findings' tables are described below, the remaining comparisons are described in detail in the main text.No primary outcome data were available when acupuncture was compared with placebo, There was no clear evidence of differences between groups for anxiodepressive symptoms (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.73 to 1.40; one study, 36 women, very low-quality evidence), spontaneous abortion (RR 0.48, 95% CI 0.05 to 5.03; one study, 57 women, low-quality evidence), preterm birth (RR 0.12, 95% CI 0.01 to 2.26; one study, 36 women, low-quality evidence), or perinatal death (RR 0.57, 95% CI 0.04 to 8.30; one study, 36 women, low-quality evidence).There was insufficient evidence to identify clear differences between acupuncture and metoclopramide in a study with 81 participants regarding reduction/cessation in nausea or vomiting (RR 1.40, 95% CI 0.79 to 2.49 and RR 1.51, 95% CI 0.92 to 2.48, respectively; very low-quality evidence).In a study with 92 participants, women taking vitamin B6 had a slightly longer hospital stay compared with placebo (mean difference (MD) 0.80 days, 95% CI 0.08 to 1.52, moderate-quality evidence). There was insufficient evidence to demonstrate a difference in other outcomes including mean number of episodes of emesis (MD 0.50, 95% CI -0.40 to 1.40, low-quality evidence) or side effects.A comparison between metoclopramide and ondansetron identified no clear difference in the severity of nausea or vomiting (MD 1.70, 95% CI -0.15 to 3.55, and MD -0.10, 95% CI -1.63 to 1.43; one study, 83 women, respectively, very low-quality evidence). However, more women taking metoclopramide complained of drowsiness and dry mouth (RR 2.40, 95% CI 1.23 to 4.69, and RR 2.38, 95% CI 1.10 to 5.11, respectively; moderate-quality evidence). There were no clear differences between groups for other side effects.In a single study with 146 participants comparing metoclopramide with promethazine, more women taking promethazine reported drowsiness, dizziness, and dystonia (RR 0.70, 95% CI 0.56 to 0.87, RR 0.48, 95% CI 0.34 to 0.69, and RR 0.31, 95% CI 0.11 to 0.90, respectively, moderate-quality evidence). There were no clear differences between groups for other important outcomes including quality of life and other side effects.In a single trial with 30 women, those receiving ondansetron had no difference in duration of hospital admission compared to those receiving promethazine (MD 0.00, 95% CI -1.39 to 1.39, very low-quality evidence), although there was increased sedation with promethazine (RR 0.06, 95% CI 0.00 to 0.94, low-quality evidence) .Regarding corticosteroids, in a study with 110 participants there was no difference in days of hospital admission compared to placebo (MD -0.30, 95% CI -0.70 to 0.10; very low-quality evidence), but there was a decreased readmission rate (RR 0.69, 95% CI 0.50 to 0.94; four studies, 269 women). For other important outcomes including pregnancy complications, spontaneous abortion, stillbirth and congenital abnormalities, there was insufficient evidence to identify differences between groups (very low-quality evidence for all outcomes). In other single studies there were no clear differences between groups for preterm birth or side effects (very low-quality evidence).For hydrocortisone compared with metoclopramide, no data were available for primary outcomes and there was no difference in the readmission rate (RR 0.08, 95% CI 0.00 to 1.28;one study, 40 women).In a study with 80 women, compared to promethazine, those receiving prednisolone had increased nausea at 48 hours (RR 2.00, 95% CI 1.08 to 3.72; low-quality evidence), but not at 17 days (RR 0.81, 95% CI 0.58 to 1.15, very low-quality evidence). There was no clear difference in the number of episodes of emesis or subjective improvement in nausea/vomiting. There was insufficient evidence to identify differences between groups for stillbirth and neonatal death and preterm birth. AUTHORS' CONCLUSIONS: On the basis of this review, there is little high-quality and consistent evidence supporting any one intervention, which should be taken into account when making management decisions. There was also very limited reporting on the economic impact of hyperemesis gravidarum and the impact that interventions may have.The limitations in interpreting the results of the included studies highlights the importance of consistency in the definition of hyperemesis gravidarum, the use of validated outcome measures, and the need for larger placebo-controlled trials.

A Randomized Controlled Double Blind Trial of Ciclosporin versus Prednisolone in the Management of Leprosy Patients with New Type 1 Reaction, in Ethiopia.

BACKGROUND: Leprosy Type 1 (T1R) reactions are immune-mediated events leading to nerve damage and preventable disability affecting hands, feet and eyes. Type 1 Reactions are treated with oral corticosteroids. There is little evidence on alternative treatments for patients who do not respond to steroids or experience steroid adverse effects. We report the results of a randomized controlled trial testing the efficacy and adverse effect profile of ciclosporin and prednisolone (CnP) in comparison to prednisolone only (P) in patients with new T1R in Ethiopia. Ciclosporin is a potent immunosuppressant. Outcomes were measured using a clinical severity score, recurrence rate, adverse events and quality of life. RESULTS: Seventy three patients with new T1R were randomized to receive CnP or P for 20 weeks. Recovery rates in skin signs was similar in both groups (91% vs 88%). Improvements in nerve function both, new and old, sensory (66% vs 49%) and motor (75% vs 74%) loss were higher (but not significantly so) in the patients on CnP. Recurrences rates of T1R (85%) were high in both groups, and recurrences occurred significantly earlier (8 weeks) in patients CnP, who needed 10% more additional prednisolone. Serious major and minor adverse events rates were similar in patients in the two treatment arms of the study. Both groups had a significant improvement in their quality of life after the study, measured by the SF-36. CONCLUSIONS: This is the first double-blind RCT assessing ciclosporin, in the management of T1R in Africa. Ciclosporin could be a safe alternative second-line drug for patients with T1R who are not improving with prednisolone or are experiencing adverse events related to prednisolone. This study illustrates the difficulty in switching off leprosy inflammation. Better treatment agents for leprosy patients with reactions and nerve damage are needed.

Extremely high HIV-1 viral load in a patient with undiagnosed clinical indicator disease for HIV infection.

We report a case of a new diagnosis of HIV with an extremely high viral load presenting with HIV encephalopathy, in a 54-year-old woman who had been treated with 2 years of extended high-dose immunosuppressant therapy for a recalcitrant pruritic rash before diagnosis.

Successful Treatment of a Child With Extensively Drug-Resistant Tuberculous Meningitis.

Unlike in pulmonary multidrug-resistant (MDR) tuberculosis, the clinical outcome of MDR tuberculous meningitis (TBM) in children, including extensively drug-resistant tuberculosis, is poor and management is challenging. We report the successful treatment of a case of extensively drug-resistant TBM in a 4-year-old girl, and we discuss implications for tuberculosis diagnosis and chemotherapy.

Achyranthes bidentata extract exerts osteoprotective effects on steroid-induced osteonecrosis of the femoral head in rats by regulating RANKL/RANK/OPG signaling.

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) presents great challenges due to the various effects of steroids on multi-system pathways involved into osteoblast differentiation, osteoblast and osteoclast apoptosis, lipid metabolism, calcium metabolism and coagulation. As one of the most frequently used herbs in Traditional Chinese Medicine formulas that are prescribed for the regulation of bone and mineral metabolism, the therapeutic effects of Achyranthes bidentata on steroid-induced ONFH remain unclear. Thus, the aim of the current study was to verify whether Achyranthes bidentata extract (ABE) can be used to prevent steroid-induced ONFH and to investigate its underlying pharmacological mechanisms. METHODS: Steroid-induced ONFH rat models were established to evaluate the effects of ABE treatment on osteonecrotic changes and repair processes. Microfocal computed tomography (Micro-CT) was performed to assess the effects of ABE treatment on bone mass, microstructure, and vascularization. Then, the effects of ABE treatment on osteoclast differentiation and bone formation were also evaluated in vivo and in vitro. In addition, receptor activator of nuclear factor kappa B (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) expression in sera, femoral heads and bone marrow-derived mesenchymal stem cells (BMSCs) were detected at both protein and mRNA levels. RESULTS: The ratio of empty lacuna, adipose tissue area, and adipocyte perimeter in the bone marrow were markedly lower in the ABE treatment groups than in the model group. Micro-CT evaluation indicated that ABE treatment could improve the microstructure of the trabecular bone, increase bone mineral density and promote vascularization in steroid-induced ONFH rats. Moreover, ABE treatment inhibited osteoclast differentiation and activated bone formation markers. Interestingly, OPG downregulation, RANK and RANKL upregulation, and an increased ratio of RANKL to OPG in sera and necrotic femoral head could be reversed by ABE treatment, which also effectively inhibited RANKL-induced osteoclast differentiation and regulated RANKL and OPG expression of in vitro. CONCLUSION: ABE may prevent steroid-induced ONFH and alleviate steroid-induced bone deterioration by regulating the RANKL/RANK/OPG signaling pathway.

Moderate zinc supplementation during prolonged steroid therapy exacerbates bone loss in rats.

The present study was conducted to understand the influence of zinc on bone mineral metabolism in prednisolone-treated rats. Disturbance in bone mineral metabolism was induced in rats by subjecting them to prednisolone treatment for a period of 8 weeks. Female rats aged 6-8 weeks weighing 150 to 200 g were divided into four treatment groups, viz., normal control, prednisolone-treated (40 mg/kg body weight orally, thrice a week), zinc-treated (227 mg/L in drinking water, daily), and combined prednisolone + zinc-treated groups. Parameters such as changes in mineral levels in the bone and serum, bone mineral density (BMD), bone mineral content (BMC), and bone 99m-technetium-labeled methylene diphosphonate ((99m)Tc-MDP) uptake were studied in various treatment groups. Prednisolone treatment caused an appreciable decrease in calcium levels both in the bone and serum and also in bone dry weight, BMC, and BMD in rats. Prednisolone-treated rats when supplemented with zinc showed further reduction in calcium levels, bone dry weight, BMD, and BMC. The study therefore revealed that moderate intake of zinc as a nutritional supplement during steroid therapy could enhance calcium deficiency in the body and accelerate bone loss.