Detection of significant liver fibrosis in Chinese psoriasis patients receiving methotrexate: a comparison between transient elastography and liver histology.

INTRODUCTION: Methotrexate (MTX) is effective for treating psoriasis and psoriatic arthritis, but its potential hepatoxicity remains a concern. Liver biopsy, the gold standard for detecting MTX-induced liver injury, is invasive and carries considerable risk. Transient elastography (TE) offers a non-invasive alternative for detecting advanced liver fibrosis. This study investigated the performance of TE in detecting MTX-induced liver fibrosis among Chinese psoriasis patients, compared with liver biopsy. METHODS: This study included adult patients with clinical psoriasis. Liver stiffness measurement using TE was performed in patients receiving MTX. Exclusion criteria were known liver cirrhosis, positive viral hepatitis carrier status, or conditions influencing TE performance. Liver biopsy was performed when liver stiffness was ≥7.1 kilopascals (kPa) or when the total cumulative dose (TCD) of MTX was ≥3.5 g. RESULTS: A total of 228 patients were screened; among 34 patients who met the inclusion criteria, nine (26.5%) had significant liver fibrosis (Roenigk grade ≥3a). The area under the receiver operating characteristic curve was 0.76 (95% confidence interval=0.59-0.93; P=0.021), indicating that TE had satisfactory performance in detecting liver fibrosis. A cut-off value of 7.1 kPa of liver stiffness yielded 100% sensitivity and 68% specificity. Liver fibrosis was not correlated with the TCD of MTX or the duration of MTX use; it was significantly correlated with obesity and diabetes status (body mass index ≥30 kg/m2, waist circumference ≥138 cm, and glycated haemoglobin level ≥7.8%). CONCLUSION: Transient elastography is reliable and superior to the TCD for detecting liver fibrosis in Chinese psoriasis patients receiving MTX. Liver biopsy should be reserved for high-risk patients or patients with liver stiffness ≥11.7 kPa on TE.

The effect of subchondral oedema in T2-weighted Dixon MRI sequence evaluation of sacroiliac joint erosion in axial spondyloarthropathy.

AIM: To evaluate the effect of subchondral oedema in T2-weighted Dixon magnetic resonance imaging (MRI) sequence evaluation of sacroiliac joint erosion in patients with axial spondyloarthropathy. MATERIALS AND METHODS: Twenty patients diagnosed with axial spondyloarthritis underwent MRI at a tertiary referral centre from December 2019 to March 2021 were included. In-phase, opposed-phase and fat-only images were scored by two musculoskeletal radiologists independently for the presence of erosions in eight sacroiliac joint quadrants. Sensitivity, specificity and areas under the curve (AUC) of the receiver operating characteristic curve were determined using T1W sequence as reference standard. Intra-observer and interobserver reliability were calculated using Cohen's kappa coefficient. RESULTS: The diagnostic performance of fat-only and in-phase images were similar (AUC 0.857-0.902 and 0.828-0.868) and better than opposed-phase images (AUC 0.613-0.658). The interobserver reliability of fat-only and in-phase images were substantial (k = 0.747 and 0.712), and moderate for opposed-phase images (k = 0.417). Intra-observer reliability was almost perfect for all the images. In the subgroup analysis, the specificity and AUC for oedema-positive group were lower than oedema-negative group in all image sets. Interobserver reliability was substantial for fat-only and in-phase images in both groups, but slight and moderate for the opposed-phase oedema-positive and negative groups, respectively. CONCLUSION: The presence of subchondral oedema in active sacroiliitis decreased the diagnostic accuracy of sacroiliac joint erosion detection on T2W Dixon MRI images.

Sequence and Observer Variability in Gadoxectic Acid-Enhanced MRI Lesion Measurements in Hepatocellular Carcinoma.

RATIONALE AND OBJECTIVES: The purpose of the study was to investigate interobserver and intersequence variability in measuring hepatocellular carcinoma on magnetic resonance imaging (MRI). METHODS AND MATERIALS: Twenty treatment-naïve lesions on Gadoxetic Acid enhanced MRI scans from 20 patients were retrospectively measured by six reviewers with different levels of experience, twice, six weeks apart, on eight different MRI sequences, in randomized order. The sequences include arterial, hepatobiliary, transitional, portal venous, T2, and diffusion weighted images. The single longest diameter (SLD) and longest diameter perpendicular to the longest overall diameter were measured on axial images and products of diameters calculated in accordance to response evaluation criteria in solid tumors v1.1 and World Health Organization response criteria respectively. Lesion-wise intraclass correlation coefficients were used to estimate measurement agreement. RESULTS: All intraclass correlation coefficients were greater than 0.95. No substantive differences between SLD and products of diameters metrics. Means (∼2.8 mm, SLD) and standard deviations (∼2 mm, SLD) were similar across sequences and observers. Similarly, pairwise comparison between observers grouped by experience showed statistically significant differences, but the effect size was minor (∼2 mm). Arterial and HPB-weighted images had similar mean dimensions (2.76 cm) while the smallest mean was in the transitional phase (2.62 cm). A lesion was not measured on 140 occasions (7%), mostly in ADC. CONCLUSION: There is high interobserver and intersequence reliability despite small differences between observers based on experience level. Our results suggest that accurate measurements can be made on arterial phase despite the possibility of indistinct margins. Lesions, however, are more likely to be missed on diffusion-related sequences.

Feasibility of Implementing Chronic Care Model in the Malaysian Public Primary Care Setting.

INTRODUCTION: Non-communicable diseases (NCD) is a global health threat. the Chronic Care Model (CCM) was proven effective in improving NCD management and outcomes in developed countries. Evidence from developing countries including Malaysia is limited and feasibility of CCM implementation has not been assessed. this study intends to assess the feasibility of public primary health care clinics (PHC) in providing care according to the CCM. METHODOLOGY: A cross-sectional survey was conducted to assess the public PHC ability to implement the components of CCM. All public PHC with Family Medicine Specialist in Selangor and Kuala Lumpur were invited to participate. A site feasibility questionnaire was distributed to collect site investigator and clinic information as well as delivery of care for diabetes and hypertension. RESULTS: there were a total of 34 public PHC invited to participate with a response rate of 100%. there were 20 urban and 14 suburban clinics. the average number of patients seen per day ranged between 250-1000 patients. the clinic has a good mix of multidisciplinary team members. All clinics had a diabetic registry and 73.5% had a hypertensive registry. 23.5% had a dedicated diabetes and 26.5% had a dedicated hypertension clinic with most clinic implementing integrated care of acute and NCD cases. DISCUSSION: the implementation of the essential components of CCM is feasible in public PHCs, despite various constraints. Although variations in delivery of care exists, majority of the clinics have adequate staff that were willing to be trained and are committed to improving patient care.

Virgin olive oil, palm olein and coconut oil diets do not raise cell adhesion molecules and thrombogenicity indices in healthy Malaysian adults.

BACKGROUND/OBJECTIVES: Effects of high-protein diets that are rich in saturated fats on cell adhesion molecules, thrombogenicity and other nonlipid markers of atherosclerosis in humans have not been firmly established. We aim to investigate the effects of high-protein Malaysian diets prepared separately with virgin olive oil (OO), palm olein (PO) and coconut oil (CO) on cell adhesion molecules, lipid inflammatory mediators and thromobogenicity indices in healthy adults. METHODS: A randomized cross-over intervention with three dietary sequences, using virgin OO, PO and CO as test fats, was carried out for 5 weeks on each group consisting of 45 men and women. These test fats were incorporated separately at two-thirds of 30% fat calories into high-protein Malaysian diets. RESULTS: For fasting and nonfasting blood samples, no significant differences were observed on the effects of the three test-fat diets on thrombaxane B2 (TXB2), TXB2/PGF1α ratios and soluble intracellular and vascular cell adhesion molecules. The OO diet induced significantly lower (P<0.05) plasma leukotriene B4 (LTB4) compared with the other two test diets, whereas PGF1α concentrations were significantly higher (P<0.05) at the end of the PO diet compared with the OO diet. CONCLUSION: Diets rich in saturated fatty acids from either PO or CO and high in monounsaturated oleic acid from virgin OO do not alter the thrombogenicity indices-cellular adhesion molecules, thromboxane B2 (TXB2) and TXB2/prostacyclin (PGF1α) ratios. However, the OO diet lowered plasma proinflammatory LTB4, whereas the PO diet raised the antiaggregatory plasma PGF1α in healthy Malaysian adults. This trial was registered at clinicaltrials.gov as NCT 00941837.

Community-based cardiovascular Risk Factors Intervention Strategies (CORFIS) in managing hypertension: A pragmatic non-randomised controlled trial.

BACKGROUND: Hypertension is the number one cardiovascular risk factor in Malaysia. This study aimed to evaluate the effectiveness of a Community-Based Cardiovascular Risk Factors Intervention Strategies (CORFIS) in the management of hypertension in primary care. METHODS: This is a pragmatic, non-randomized controlled trial. Seventy general practitioners (GPs) were selected to provide either CORFIS (44 GPs) or conventional care (26 GPs) for 6 months. A total of 486 hypertensive patients were recruited; 309 were in the intervention and 177 in the control groups. Primary outcome was the proportion of hypertensive patients who achieved target blood pressure (BP) of <140/90mmHg (for those without diabetes mellitus) and <130/80mmHg (with diabetes mellitus). Secondary outcomes include change in the mean/median BP at 6-month as compared to baseline. RESULTS: The proportion of hypertensive patients who achieved target BP at 6-month was significantly higher in the CORFIS arm (69.6%) as compared to the control arm (57.6%), P=0.008. Amongst those who had uncontrolled BP at baseline, the proportion who achieved target BP at 6-month was also significantly higher in the CORFIS arm (56.6%) as compared to the control arm (34.1%), p<0.001. There was no difference in the patients who had already achieved BP control at baseline. There were significant reductions in SBP in the CORFIS arm (median -9.0mmHg; -60 to 50) versus control (median -2mmHg; -50 to 48), p=0.003; as well as in DBP (CORFIS arm: median -6.0mmHg; ranged from -53 to 30 versus control arm: median 0.0mmHg; ranged from -42 to 30), p<0.001. CONCLUSIONS: Patients who received CORFIS care demonstrated significant improvements in achieving target BP.

Multiple indomethacin-induced colonic perforations in an adolescent.

Colonic perforation is an uncommon cause of acute abdomen in paediatric patients, and can present a diagnostic enigma as well as management challenge to the paediatric surgeon. An adolescent developed multiple colonic perforations following a short course of oral indomethacin, requiring emergency hemicolectomy. This is the youngest known case of enteral non-steroidal anti-inflammatory drug (NSAID)-mediated large bowel injury. We review current evidence on NSAID-related enteropathy, and postulate potentiating mechanisms that may have accounted for the unusually rapid clinical course of our patient.

Aggressive osteoblastoma of the proximal humerus.

A nine-year-old boy presented with increasingly worsening right shoulder pain of 18 months' duration. On physical examination, there was a tender firm swelling over the right upper arm. Radiographs showed a large osteolytic lesion in the proximal humeral diaphysis, with prominent mixed acute-on-chronic periosteal reaction in a lamellar fashion. There was a pathological fracture. The lesion appeared to be radiographically aggressive in nature. Bone scintiscan showed solitary marked uptake. On-table frozen section histopathological examination of the lesion showed an osteoblastic lesion with aggressive features. Completion curettage and high speed burring of the cavity was performed. In view of the patient's young age, which required a biological solution, and potential for local recurrence, that necessitated a radiopaque filler, the lesion was packed with a calcium phosphate cement paste. The final diagnosis was osteoblastoma with aggressive features. The patient remained well on follow-up to date. The filler continues to be remodelled to native tissue and there is no evidence of local recurrence. Osteoblastoma is a relatively rare benign tumour that typically occurs in the posterior elements of the vertebral column. The humerus is a very rare site of disease in the appendicular skeleton, and poses a diagnostic dilemma which implicates the possibility of osteogenic sarcoma.

Acute bacterial parotitis following acute stroke.

Acute bacterial parotitis (ABP) is a relatively uncommon condition that tends to occur in debilitated older patients. We report a case of an older woman that presented with an acute intracerebral hemorrhage who developed ABP. This morbidity led to endotracheal intubation, mechanical ventilation, tracheostomy and gastrostomy, all of which were not initially needed. We discuss the proposed physiopathology and etiopathogenesis of ABP in adults.

Preoperative and intraoperative diagnosis of low-grade adenosquamous carcinoma of the breast: potential diagnostic pitfalls.

AIMS: Low-grade adenosquamous carcinoma (LGAC), a rare variant of metaplastic breast cancer, may mimic benign or other low-grade malignant lesions histologically. Diagnostic difficulty may be encountered when evaluating breast cytology, core needle biopsy or intraoperative frozen section specimens. METHODS AND RESULTS: Pathology reports, cytology aspirates and histological slides of LGAC diagnosed at the Department of Pathology, Singapore General Hospital, were reviewed. Four cases of LGAC were analysed. Cytology from the first case showed atypical cells and the subsequent surgical excision specimen showed a complex sclerosing lesion with LGAC. The second and third cases were investigated by core needle biopsies: the preoperative histological features were suggestive of but not diagnostic of LGAC, until further excision biopsies were performed. The fourth case entailed a frozen section specimen, for which definitive diagnosis was deferred to paraffins. The patients remained well with no evidence of recurrent disease to date. CONCLUSIONS: When limited material, in the form of needle aspirates, core biopsy specimens or frozen sections, is submitted for histology, making a diagnosis of LGAC is not only challenging, but may be impossible. In difficult cases, careful pathological assessment, clinicopathological correlation and follow-up or complete excision biopsy may prove invaluable in establishing a definitive diagnosis.

"Rhabdoid meningioma" lacking malignant features. Report of two cases.

We report 2 cases of meningiomas with rhabdoid morphology but lacking histological features of malignancy. Both occurred in adult women, one arising from the superior surface of the tentorium and the other in the Sylvian fissure. The tumors showed light microscopic, immunohistochemical and ultrastructural evidence of meningothelial differentiation together with diffuse or focal areas exhibiting rhabdoid morphology. The rhabdoid areas were characterized by cells with large cytoplasmic eosinophilic inclusions and large eccentric nuclei. Both cases showed areas with sheet-like growth and one had macronucleoli and brain invasion. The same case showed areas of necrosis that most likely related to pre-operative arterial embolization. Unlike most cases reported in the literature, these "rhabdoid meningiomas" lacked significant mitotic activity or other atypical features. The diagnostic and prognostic significance of this tumor entity is discussed along with a review of the literature.

Herpes zoster and postherpetic neuralgia in the elderly.

This article describes herpes zoster (HZ), its cause, diagnosis, treatment, and associated complications. Postherpetic neuralgia (PHN), the most common complication of HZ, is the primary focus of the discussion. PHN is defined broadly as chronic pain that persists after the characteristic vesicular rash of HZ has resolved.

Clinical and radiological aspects in Melnick-Needles syndrome.

Melnick-Needles syndrome is an X-linked dominant bone dysplasia, lethal in males, characterized by a typical facies and characteristic radiological findings: including sclerosis of skull base and mastoids. S-shaped appearance of tibia; cortical irregularities with a ribbon appearance of the ribs. About 48 well-documented cases have been reported, most of them were sporadic. Parental transmission has been published in only 11 kindreds. We are presenting the first Brazilian family with mother-daughter transmission. The proposita presented the typical clinical and radiological features with characteristic facies, severe thoracic cage restriction and pulmonary hypertension. Her mother was more mildly affected.

A case report: special needs of hospitalized elders.

A case report is used to discuss common problems and complications of hospitalized elders. The report also illustrates the need for proactive hospital staff who are knowledgeable about the special needs of the aging population if this group is to be cared for successfully. The geriatric resource nurse model involves informal unit-based education aimed at expanding staff nurses' geriatric knowledge and is one of several models sponsored by the Hartford Foundation to improve care of the hospitalized elderly. Teaching rounds between geriatric resource nurses and advanced practice nurses are a primary feature of this model.

The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding.

We recently reported the positional cloning of a candidate gene for hereditary hemochromatosis called HFE. The gene product, a member of the major histocompatibility complex class I-like family, was found to have a mutation, Cys-282 --> Tyr (C282Y), in 85% of patient chromosomes. This mutation eliminates the ability of HFE to associate with beta2-microglobulin (beta2m) and prevents cell-surface expression. A second mutation that has no effect on beta2m association, H63D, was found in eight out of nine patients heterozygous for the C282Y mutant. In this report, we demonstrate in cultured 293 cells overexpressing wild-type or mutant HFE proteins that both the wild-type and H63D HFE proteins form stable complexes with the transferrin receptor (TfR). The C282Y mutation nearly completely prevents the association of the mutant HFE protein with the TfR. Studies on cell-associated transferrin at 37 degrees C suggest that the overexpressed wild-type HFE protein decreases the affinity of the TfR for transferrin. The overexpressed H63D protein does not have this effect, providing the first direct evidence for a functional consequence of the H63D mutation. Addition of soluble wild-type HFE/beta2m heterodimers to cultured cells also decreased the apparent affinity of the TfR for its ligand under steady-state conditions, both in 293 cells and in HeLa cells. Furthermore, at 4 degrees C, the added soluble complex of HFE/beta2m inhibited binding of transferrin to HeLa cell TfR in a concentration-dependent manner. Scatchard plots of these data indicate that the added heterodimer substantially reduced the affinity of TfR for transferrin. These results establish a molecular link between HFE and a key protein involved in iron transport, the TfR, and raise the possibility that alterations in this regulatory mechanism may play a role in the pathogenesis of hereditary hemochromatosis.

The hemochromatosis founder mutation in HLA-H disrupts beta2-microglobulin interaction and cell surface expression.

We recently reported the positional cloning of a candidate gene for hereditary hemochromatosis (HH), called HLA-H, which is a novel member of the major histocompatibility complex class I family. A mutation in this gene, cysteine 282 --> tyrosine (C282Y), was found to be present in 83% of HH patient DNAs, while a second variant, histidine 63 --> aspartate (H63D), was enriched in patients heterozygous for C282Y. The functional relevance of either mutation has not been described. Co-immunoprecipitation studies of cell lysates from human embryonic kidney cells transfected with wild-type or mutant HLA-H cDNA demonstrate that wild-type HLA-H binds beta2-microglobulin and that the C282Y mutation, but not the H63D mutation, completely abrogates this interaction. Immunofluorescence labeling and subcellular fractionations demonstrate that while the wild-type and H63D HLA-H proteins are expressed on the cell surface, the C282Y mutant protein is localized exclusively intracellularly. This report describes the first functional significance of the C282Y mutation by suggesting that an abnormality in protein trafficking and/or cell-surface expression of HLA-H leads to HH disease.

A 1.1-Mb transcript map of the hereditary hemochromatosis locus.

In the process of positionally cloning a candidate gene responsible for hereditary hemochromatosis (HH), we constructed a 1.1-Mb transcript map of the region of human chromosome 6p that lies 4.5 Mb telomeric to HLA-A. A combination of three gene-finding techniques, direct cDNA selection, exon trapping, and sample sequencing, were used initially for a saturation screening of the 1.1-Mb region for expressed sequence fragments. As genetic analysis further narrowed the HH candidate locus, we sequenced completely 0.25 Mb of genomic DNA as a final measure to identify all genes. Besides the novel MHC class 1-like HH candidate gene HLA-H, we identified a family of five butyrophilin-related sequences, two genes with structural similarity to a type 1 sodium phosphate transporter, 12 novel histone genes, and a gene we named RoRet based on its strong similarity to the 52-kD Ro/SSA lupus and Sjogren's syndrome auto-antigen and the RET finger protein. Several members of the butyrophilin family and the RoRet gene share an exon of common evolutionary origin called B30-2. The B30-2 exon was originally isolated from the HLA class 1 region, yet has apparently "shuffled" into several genes along the chromosome telomeric to the MHC. The conservation of the B30-2 exon in several novel genes and the previously described amino acid homology of HLA-H to MHC class 1 molecules provide further support that this gene-rich region of 6p21.3 is related to the MHC. Finally, we performed an analysis of the four approaches for gene finding and conclude that direct selection provides the most effective probes for cDNA screening, and that as much as 30% of ESTs in this 1.1-Mb region may be derived from noncoding genomic DNA.