Sarcopenia, body composition and factors associated with variceal gastrointestinal bleeding and splenectomy in hepatosplenic schistosomiasis mansoni.

BACKGROUND: Sarcopenia is a common complication of cirrhosis and an important predictor of morbimortality. We aimed to determine the prevalence of sarcopenia and its associated factors in hepatosplenic schistosomiasis (HSS) as well as to evaluate whether muscle mass and function are associated with variceal upper gastrointestinal bleeding (VUGIB) and previous splenectomy in subjects without other liver diseases. METHODS: We conducted a cross-sectional study including adults with HSS who underwent clinical, biochemical, anthropometric, muscle strength and physical performance evaluations and were submitted to bioelectrical impedance analysis and abdominal ultrasound. Sarcopenia was diagnosed according to the 2019 European consensus criteria. RESULTS: A total of 66 patients with HSS (62.1% male; mean age 48.8±8.6 y) were included. Overall, six subjects (9.1%) were diagnosed with probable sarcopenia and none had confirmed sarcopenia. Fat-free body mass index (BMI) was independently associated with VUGIB (odds ratio 0.701 [95% confidence interval 0.51 to 0.96]; p=0.025). Compared with patients who did not undergo surgery, individuals who underwent esophagogastric devascularization combined with splenectomy (EGDS) had higher serum lipid levels, fat percentage and frequency of metabolic syndrome, with lower skeletal muscle mass index and hand grip strength. CONCLUSIONS: HSS mansoni seems not to cause sarcopenia. However, a lower fat-free BMI was associated with previous VUGIB and the subgroup of patients who underwent EGDS presented higher lipid levels, fat percentage and frequency of metabolic syndrome and lower muscle mass and function.

Liver stiffness is able to differentiate hepatosplenic Schistosomiasis mansoni from liver cirrhosis and spleen stiffness may be a predictor of variceal bleeding in hepatosplenic schistosomiasis.

BACKGROUND: Ultrasonography is limited for differentiating portal hypertension due to liver cirrhosis from that secondary to hepatosplenic schistosomiasis (HSS). We aimed to investigate the role of transient elastography (TE) in differentiating HSS mansoni from cirrhosis and the factors associated with liver and spleen stiffness (LS and SS) in HSS. METHOD: A cross-sectional study was conducted including patients with HSS mansoni (n=29) and liver cirrhosis due to non-alcoholic steatohepatitis (n=23). All patients underwent TE and those with HSS were assessed by the Niamey protocol. RESULTS: HSS subjects presented lower median LS (9.6 vs 21.3 Kpa, p<0.001) and liver controlled attenuation parameter (229 vs 274 dB/m, p=0.010) than cirrhosis subjects, in addition to higher SS (73.5 vs 42.2 Kpa, p=0.002). The area under the receiver operating characteristic curve for detecting cirrhosis by LS was 0.947 (95% CI 0.89 to 1.00, p<0.001), with an optimal cut-off of 11.75 Kpa. In HSS subjects, higher SS was associated with the presence of the following: diabetes mellitus (p=0.036), metabolic syndrome (p=0.043), esophageal varices (p=0.001), portal vein thrombosis (p=0.047) and previous variceal bleeding (p=0.011). In HSS patients without portal vein thrombosis, variceal bleeding was associated with higher SS (p=0.018). Niamey categories were not associated with LS (p=0.676) or SS (p=0.504). CONCLUSION: TE can play a role in differentiating HSS from cirrhosis, especially by LS. SS may be further investigated for predicting complications in HSS.

Crosstalk Between Plasma Cytokines, Inflammation, and Liver Damage as a New Strategy to Monitoring NAFLD Progression.

Cytokines are involved in the immunopathogenesis of nonalcoholic fatty liver disease (NAFLD), but the relationship between them and clinical parameters of NAFLD progression is still unknown. Using flow cytometry, we evaluated the plasma levels of IL-1ß, IL-6, IL-12, TNF and IL-10 and their association with clinical and biochemical parameters of liver function during simple steatosis (NAFL) and nonalcoholic steatohepatitis (NASH) in biopsy-proven patients. The NASH patients showed higher levels of IL-6 associated with a lower IL-10/IL-6 ratio. Besides heatmaps were similar in the NAFL and NASH groups, the same did not occur in signature curves, the NASH patients were high producers to IL-12 and IL-6 while the NAFL patients were not high producers of any cytokines evaluated. Integrative biomarker network analysis revealed that cytokines are differently correlated with clinical parameters, while IL-12, IL-10 presented moderate and negative correlations with glycemic and lipid profile in the NAFL group. The NASH group IL-12 and TNF revealed stronger and positive correlations with transient elastography parameters and NAFLD liver fibrosis score. These data suggest that IL-6 and IL-10 might act in chronic inflammation and insulin resistance whereas IL-12 and TNF may be involved in promoting liver damage and NAFLD progression. Plasma concentration analysis of these molecules and their association with clinical parameters can be used as new biomarkers to monitoring NAFLD progression and to reflect NASH development.

Identification of clinical and radiographic predictors of central nervous system injury in genetic skeletal disorders.

Some studies report neurological lesions in patients with genetic skeletal disorders (GSDs). However, none of them describe the frequency of neurological lesions in a large sample of patients or investigate the associations between clinical and/or radiological central nervous system (CNS) injury and clinical, anthropometric and imaging parameters. The project was approved by the institution's ethics committee (CAAE 49433215.5.0000.0022). In this cross-sectional observational analysis study, 272 patients aged four or more years with clinically and radiologically confirmed GSDs were prospectively included. Genetic testing confirmed the diagnosis in the FGFR3 chondrodysplasias group. All patients underwent blinded and independent clinical, anthropometric and neuroaxis imaging evaluations. Information on the presence of headache, neuropsychomotor development (NPMD), low back pain, joint deformity, ligament laxity and lower limb discrepancy was collected. Imaging abnormalities of the axial skeleton and CNS were investigated by whole spine digital radiography, craniocervical junction CT and brain and spine MRI. The diagnostic criteria for CNS injury were abnormal clinical and/or radiographic examination of the CNS. Brain injury included malacia, encephalopathies and malformation. Spinal cord injury included malacia, hydrosyringomyelia and spinal cord injury without radiographic abnormalities. CNS injury was diagnosed in more than 25% of GSD patients. Spinal cord injury was found in 21.7% of patients, and brain injury was found in 5.9%. The presence of low back pain, os odontoideum and abnormal NPMD remained independently associated with CNS injury in the multivariable analysis. Early identification of these abnormalities may have some role in preventing compressive CNS injury, which is a priority in GSD patients.

Portal vein thrombosis in patients with hepatosplenic schistosomiasis who underwent oesophagogastric devascularization combined with splenectomy.

BACKGROUND: Portal vein thrombosis (PVT) has been described in nearly 50% of patients who underwent oesophagogastric devascularization combined with splenectomy (EGDS), but no previous study has compared its occurrence in surgical and non-surgical groups. This study aimed to investigate PVT in hepatosplenic schistosomiasis (HSS) and its association with EGDS and upper variceal bleeding (UVB). METHODS: Retrospectively, 104 HSS individuals were enrolled. Following EGDS, the occurrence of PVT, mesenteric vein thrombosis (MVT), hospital admissions and UVB were recorded. RESULTS: EGDS was performed in 27 (26%) patients. PVT and MVT were detected in 30 (33%) and 8 (9.8%) patients, respectively. Patients who underwent EGDS were at greater risk of PVT (63% vs 19.7%; odds ratio [OR] 6.12 [95% confidence interval {CI} 2.3 to 16.1], p<0.001) when compared with a non-surgical approach. There was no significant difference in UVB occurrence and ß-blocker usage. PVT was associated with more hospital admissions (p=0.030) and higher alkaline phosphatase levels (p=0.008). UVB occurrence in patients with and without thrombosis was similar. In multivariate analysis, after adjustment, PVT was associated with the surgical approach (OR 4.56 [95% CI 1.55 to 13.38], p=0.006) and age at HSS diagnosis (OR 0.94 [95% CI 0.90 to 0.99], p=0.021). CONCLUSIONS: EGDS was not associated with a decreased frequency of UVB when compared with the non-surgical approach but was an independent risk factor for PVT.

Expression of MAPK and PI3K/AKT/mTOR Proteins according to the Chronic Liver Disease Etiology in Hepatocellular Carcinoma.

AIMS: Chronic liver disease (CLD) of different etiologies leads to hepatocellular carcinoma (HCC) by multiple mechanisms that may be translated into clinicopathological differences. We evaluated the tissue expression of the MAPK and PI3K/Akt/mTOR pathway proteins and their association with long-term outcome and other parameters, according to the etiology of the CLD, in HCC patients. METHODS: Clinicopathological data from 80 patients who underwent orthotopic liver transplantation for HCC treatment in a Brazilian referral center were compared according to CLD etiology. Event (tumor recurrence or death from any cause) occurrence and event-free survival (EFS) were analyzed. Pathway protein expression was assessed by immunohistochemistry (IHQ) in both tumor and underlying cirrhosis and by RT-PCR in tumor tissue. RESULTS: Strong expression (SE) of KRAS was more frequent in tumors arising from viral (26.8%) than the nonviral group of liver disease (7.7%, p=0.024) and also than cirrhotic parenchyma (0%, p=0.004). SE of PI3K was more frequent in tumor than in cirrhosis (p=0.048, p < 0.01), without differences in its tumor expression among etiologic groups (p=0.111). mRNA of ERK, PI3K, and BRAF was expressed in the tumor, without differences between CLD etiologies, and there was no association with IHQ findings. Older age and microvascular invasion (MIV) were the only parameters independently associated with the event. MIV was also associated with shorter EFS. CONCLUSIONS: Hepatitis B and C virus can lead to HCC by different mechanisms compared with nonviral hepatopathy. KRAS and PI3K may have a role in carcinogenesis. The prognostic and therapeutic implications need to be investigated.

Beneficial Effect of Synbiotic Supplementation on Hepatic Steatosis and Anthropometric Parameters, But Not on Gut Permeability in a Population with Nonalcoholic Steatohepatitis.

Nonalcoholic fatty liver disease is the most prevalent chronic liver disease in Western countries; it can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocarcinoma. The importance of gut-liver-adipose tissue axis has become evident and treatments targeting gut microbiota may improve inflammatory and metabolic parameters in NASH patients. In a randomized, controlled clinical trial, involving 50 biopsy-proven NASH patients, we investigated the effects of synbiotic supplementation on metabolic parameters, hepatic steatosis, intestinal permeability, small intestinal bacterial overgrowth (SIBO) and lipopolysaccharide (LPS) serum levels. Patients were separated into two groups receiving Lactobacillus reuteri with guar gum and inulin for three months and healthy balanced nutritional counseling versus nutritional counseling alone. Before and after the intervention we assessed steatosis by magnetic resonance imaging, intestinal permeability by lactulose/mannitol urinary excretion and SIBO by glucose breath testing. NASH patients presented high gut permeability, but low prevalence of SIBO. After the intervention, only the synbiotic group presented a reduction in steatosis, lost weight, diminished BMI and waist circumference measurement. Synbiotic did not improve intestinal permeability or LPS levels. We concluded that synbiotic supplementation associated with nutritional counseling seems superior to nutritional counseling alone for NASH treatment as it attenuates steatosis and may help to achieve weight loss.

The role of intestinal bacteria overgrowth in obesity-related nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. It is a progressive disorder involving a spectrum of conditions that include pure steatosis without inflammation, nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes, which may be followed by lipid peroxidation, production of reactive oxygen species and consequent inflammation. Recent studies suggest that the characteristics of the gut microbiota are altered in NAFLD, and also, that small intestinal bacterial overgrowth (SIBO) contributes to the pathogenesis of this condition. This review presents the chief findings from all the controlled studies that evaluated SIBO, gut permeability and endotoxemia in human NAFLD. We also discuss the possible mechanisms involving SIBO, lipid accumulation and development of NASH. The understanding of these mechanisms may allow the development of new targets for NASH treatment in the future.

Identification and characterization of immune complexes in the cerebrospinal fluid of patients with spinal cord schistosomiasis.

The pathogenesis of neuroschistosomiasis is largely unknown. Available evidence suggests that it depends on the presence of parasite eggs in the nervous tissue and on the host's immune response. We investigated the presence of immune complexes (ICs) in the cerebrospinal fluid (CSF) of four patients with spinal cord schistosomiasis (SCS), and performed their characterization. ICs containing soluble egg antigen of Schistosoma mansoni (SEA) were found in the CSF of all the SCS patients. To our knowledge, this is the first evidence of ICs containing schistosomal antigens in the CSF of patients with SCS. Further studies are necessary to confirm our findings and investigate the possible roles of ICs in the pathogenesis of this disease.

Clinical-epidemiologic profile of the schistosomal myeloradiculopathy in Pernambuco, Brazil.

This was a retrospective descriptive study on a series of cases of schistosomal myeloradiculopathy (SMR) and the aim was to investigate the incidence of this disease and its clinical and epidemiological characteristics in cases diagnosed at three healthcare units in Pernambuco, Brazil between 1994-2006. The data were collected by reviewing the medical records from both the neurological and paediatric outpatient clinics and wards of the Hospital Clinics, Hospital of the Restoration and Pernambuco Mother and Child Institute. To gather the data, a spinal cord schistosomiasis evaluation protocol was used. The diagnoses were based on positive epidemiological evidence of schistosomiasis, clinical findings and laboratory tests (stool parasitological examination or rectal biopsies, magnetic resonance imaging findings and cerebrospinal fluid investigations). A total of 139 cases aged between 2-83 years were found. The most important determinants of SMR were male sex (66.2%), contact with fresh water (91%), origin in endemic regions (39.5%), lower-limb muscle weakness (100%), sensory level at the lower thoracic medulla (40.3%), myeloradicular form (76%) and presence of eggs in the stool parasitological examination (48%). This sample indicates the need for intervention policies guided by diagnostic standardization, thereby avoiding disease under-notification.

A laboratory test for the diagnosis of neuroschistosomiasis.

OBJECTIVE: To provide a general description of the studies on spinal cord schistosomiasis that our team has developed in Brazil, with an emphasis on how we have planned the investigations and managed the problems. METHODS: Schistosoma mansoni is endemic in extensive areas in Brazil. We review the subject and discuss the design, development and initial evaluation of a diagnostic cerebrospinal fluid enzyme-linked immunoassay test for spinal cord schistosomiasis. RESULTS: Since the late 1980s, several clinical investigations have led to a better understanding of the natural history of this disorder and an improved characterization of its clinical presentations. Spinal cord schistosomiasis is a severe condition that typically presents as an acute/subacute low cord syndrome generally associated with the involvement of the cauda equina roots. Cerebrospinal fluid examination usually shows an inflammatory pattern, and MRI demonstrates findings of an inflammatory spinal cord lesion. Its diagnosis is largely based on clinical evidence. There is no definitive consensus on the treatment of neuroschistosomiasis, but most authors recommend the administration of praziquantel and a steroid. The outcome is variable and chiefly dependent on early treatment. The results of the cerebrospinal fluid enzyme-linked immunoassay test for schistosomal myeloradiculopathy allow the confirmation or exclusion of this disorder in a large proportion of suspected cases. DISCUSSION: Although knowledge on schistosomiasis has improved during the last two decades, several aspects of this disorder are still unknown and deserve investigation. The enzyme-linked immunoassay test in cerebrospinal fluid showed promising results, but needs validation in a new sample of subjects.

Laryngeal histoplasmosis in an immunocompetent patient from a non-endemic region: case report.

Histoplasma capsulatum infection involving the larynx is a rare manifestation, especially in immunocompetent individuals and a high index of suspicion is needed to establish the diagnosis correctly. We report a case of a 50-year-old Brazilian man who presented with progressive hoarseness and throat pain for 4 months. Laryngoscopy showed a supraglottic vegetant lesion, and the biopsies chronic granulomatous inflammation without any specific agent. A second laryngoscopy with biopsies was performed and after 17 days of incubation in specific medium, H. capsulatum was isolated. The patient was successfully treated with amphotericin B.

Immune response and pathogenesis of neuroschistosomiasis mansoni.

The involvement of the central nervous system (CNS) by schistosomes may or may not determine clinical manifestations. When symptomatic, neuroschistosomiasis (NS) is one of the most severe presentations of schistosome infection. Considering the symptomatic form, Schistosoma mansoni causes almost always spinal cord disease. Cerebral and spinal cord disorders in S. mansoni infections are inflammatory conditions of the CNS that cause mild-moderate impairment of the blood-brain barrier and intrathecal synthesis of antibodies against schistosomal antigens. Little is known about the pathogenesis of NS, but available evidence strongly suggests that it depends basically on the presence of parasite eggs in the nervous tissue and on the host's immune response against the trapped eggs. Numerous eggs surrounded by granulomas lodged together in circumscribed areas of the CNS damage the nervous tissue by both the mass effect and the egg-induced inflammatory reaction. Vasculitis of immune etiology, which causes isquemic lesions, may also play an important role in the genesis of the neurological symptoms. Although the mechanisms involved in the immunophatogenesis of NS are largely unknown, initial investigations on cerebrospinal fluid (CSF) and serum cytokine profiles suggest the occurrence of inflammation as well as a skewed Th2 immune response that probably occur both locally and systemically.

Clinical characterization of neuroschistosomiasis due to Schistosoma mansoni and its treatment.

The involvement of the central nervous system (CNS) by Schistosoma mansoni may or may not cause clinical manifestations. When symptomatic, neuroschistosomiasis mansoni (NSM) is one of the most severe presentations of this infection. The neurological manifestations are due to numerous granulomas grouped in confined areas of the spinal cord or the brain. Considering the symptomatic form, myelopathy is far more frequent than the cerebral disease. Spinal cord NSM presents as a low cord syndrome of acute/subacute progression usually associated with involvement of the cauda esquina roots. Lower limbs pain, weakness and sensory disturbance, and autonomic dysfunctions, particularly bladder dysfunction, are often present. Cerebrospinal fluid (CSF) examination generally shows an inflammatory pattern with or without eosinophils and/or IgG against schistosomal antigens. Magnetic resonance imaging (MRI) demonstrates signs of inflammatory myelopathy. Cerebral NSM presents as a slow-expanding intracranial tumor-like lesion. Its clinical manifestations are variable and depend on the increased intracranial pressure and on the site of the lesion. The diagnosis of spinal cord NSM is based on clinical evidence whereas the cerebral disease is usually diagnosed by biopsy of the nervous tissue. There is no consensus on the treatment of NSM. We discuss the literature data on this topic, and suggest a therapeutic approach based on our experience with 69 spinal cord NSM patients who have been followed up by a long period of time. Outcome is largely dependent on early treatment, particularly in the medullar disorder, and is better in cerebral NSM.

Hepatocellular carcinoma is associated with an increased risk of hepatitis B virus recurrence after liver transplantation.

BACKGROUND & AIMS: Hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) is significantly reduced by prophylaxis with hyperimmune antibody to hepatitis B surface antigen (anti-HBs) globulins (HBIG) and antiviral drugs. The role of hepatocellular carcinoma (HCC) in HBV recurrence remains unclear. We investigated the association between HCC pre-OLT and HBV recurrence post-OLT. METHODS: We studied 99 hepatitis B surface antigen-positive patients who underwent OLT for cirrhosis. The median follow-up period was 43 months. All patients received HBIG, and 51 also received lamivudine and/or adefovir. Of these 99 patients, 31 had HCC before OLT. Total HBV DNA and covalently closed circular (ccc)-DNA were measured in tumor and nontumor tissues from the explanted livers of 16 of these 31 HCC patients and, also, in a context of tumor recurrence, in 3 patients who developed HBV/HCC recurrence. RESULTS: Fourteen patients (14.1%) developed HBV recurrence within a median period of 15 months post-OLT. HCC at OLT, a pre-OLT HBV DNA viral load > or = 100,000 copies/mL, and HBIG monoprophylaxis were independently associated with HBV recurrence post-OLT. Eleven out of the 31 patients with HCC at OLT presented with HBV recurrence and 3 out of the 68 patients without HCC had HBV recurrence (P < .0001). HBV recurrence was more frequent in patients who developed HCC recurrence (7/8 patients, 87.5%) than in those who did not (4/23 patients, 17.4%) (P < .0001). In the 16 explanted livers, cccDNA was detectable in HCC cells in 11 and in nontumor cells in 12. cccDNA was detected in a context of HCC recurrence in 2 of the 3 patients tested who developed HBV/HCC recurrence. CONCLUSIONS: The associations of HCC pre-OLT, and HCC recurrence with HBV recurrence post-OLT, and the detection of HBV DNA and cccDNA in HCC suggest that HBV replication in tumor cells may contribute to HBV recurrence post-OLT.

Clinical-epidemiological profile of children with schistosomal myeloradiculopathy attended at the Instituto Materno-Infantil de Pernambuco

The most critical phase of exposure to schistosomal infection is the infancy, because of the more frequent contact with contaminated water and the immaturity of the immune system. One of the most severe presentations of this parasitosis is the involvement of the spinal cord, which prognosis is largely dependent on early diagnosis and treatment. Reports on this clinical form of schistosomiasis in children are rare in the literature. We present here the clinical-epidemiological profile of schistosomal myeloradiculopathy (SMR) from ten children who were admitted at the Instituto Materno-Infantil de Pernambuco over a five-year period. They were evaluated according to an investigation protocol. Most of these patients presented an acute neurological picture which included as the main clinical manifestations: sphincteral disorders, low back and lower limbs pain, paresthesia, lower limbs muscle weakness and absence of deep tendon reflex, and impairment of the gait. The diagnosis was presumptive in the majority of the cases. This study emphasizes the importance of considering the diagnosis of SMR in pediatric patients coming from endemic areas who present a low cord syndrome, in order to start the appropriate therapy and avoid future complications.

Prostate adenocarcinoma manifesting as generalized lymphadenopathy.

Generalized lymphadenopathy is a rare manifestation of metastatic prostate cancer. Here, we report the case of a 65-year-old patient with supraclavicular, mediastinal, hilar, and retroperitoneal lymphadenopathy and pulmonary infiltration, which suggested the diagnosis of lymphoma. There were no urinary symptoms, and the serum prostate-specific antigen (PSA) was only mildly increased with a normal free PSA. A biopsy of the supraclavicular lymph node was compatible with adenocarcinoma, whose prostatic origin was shown by immunohistochemical staining with PSA. The origin of the primary tumor was confirmed by directed prostate biopsy. We emphasize that a suspicion of prostate cancer in men with adenocarcinoma of undetermined origin is important for an adequate diagnostic and therapeutic approach.

Clinical-epidemiological profile of children with schistosomal myeloradiculopathy attended at the Instituto Materno-Infantil de Pernambuco.

The most critical phase of exposure to schistosomal infection is the infancy, because of the more frequent contact with contaminated water and the immaturity of the immune system. One of the most severe presentations of this parasitosis is the involvement of the spinal cord, which prognosis is largely dependent on early diagnosis and treatment. Reports on this clinical form of schistosomiasis in children are rare in the literature. We present here the clinical-epidemiological profile of schistosomal myeloradiculopathy (SMR) from ten children who were admitted at the Instituto Materno-Infantil de Pernambuco over a five-year period. They were evaluated according to an investigation protocol. Most of these patients presented an acute neurological picture which included as the main clinical manifestations: sphincteral disorders, low back and lower limbs pain, paresthesia, lower limbs muscle weakness and absence of deep tendon reflex, and impairment of the gait. The diagnosis was presumptive in the majority of the cases. This study emphasizes the importance of considering the diagnosis of SMR in pediatric patients coming from endemic areas who present a low cord syndrome, in order to start the appropriate therapy and avoid future complications.

Spinal cord schistosomiasis: a prospective study of 63 cases emphasizing clinical and therapeutic aspects.

A prospective study was conducted on 63 patients with schistosomal myeloradiculopathy admitted to a university hospital in Brazil. They were evaluated according to a protocol and treated with corticosteroid and praziquantel. The disease, in general, presented as a lower cord syndrome of acute progression characterized by motor, sensory and autonomic dysfunctions. The severity of the clinical picture was different among the patients, but the symptoms were quite constant. Cerebrospinal fluid examination showed an inflammatory pattern with or without eosinophils and/or IgG against schistosomal antigens. The most frequent alterations detected by imaging methods were enlargement of the medullary cone and of the roots of the cauda equina. Schistosome egg counts suggested a low parasite burden in 71.6% of the cases. Outcome was favorable in 38 (60.3%) patients and improvement usually started within the first 48 h after commencing on corticoid and was faster during the early period of treatment.