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.

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.

A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis.

Hereditary haemochromatosis (HH), which affects some 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals of Northern European descent, results in multi-organ dysfunction caused by increased iron deposition, and is treatable if detected early. Using linkage-disequilibrium and full haplotype analysis, we have identified a 250-kilobase region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical-by-descent in 85% of patient chromosomes. Within this region, we have identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations. One of these is predicted to inactivate this class of proteins and was found homozygous in 83% of 178 patients. A role of this gene in haemochromatosis is supported by the frequency and nature of the major mutation and prior studies implicating MHC class I-like proteins in iron metabolism.

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.

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.

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.

Monoclonal antibodies to cell surface antigens shared by chemically induced mouse bladder carcinomas.

Rats were immunized with cultured cells from chemically induced transitional cell carcinomas of the mouse urinary bladder, and their spleen cells were hybridized with NS-1 mouse myeloma cells. Following initial screening of antibodies made by hybridoma clones, the tissue distribution of antigens defined by the antibodies was established by using a peroxidase-antiperoxidase technique with frozen sections of a variety of mouse tumors, as well as normal adult and embryonic tissues. Two antibodies were identified which detected antigens with bladder carcinoma specificity. One antibody (3B12) reacted weakly with epithelial cells from several sources, including normal bladder, while the second antibody (6.10), which bound strongly to bladder carcinoma cells, was negative on bladder epithelium and bound (weakly) to only a small fraction of all epithelial cells tested except for epidermal cells and periosteum from embryos. Both antibodies should be useful to assess the immunotherapeutic and immunoprophylactic effects of monoclonal antibodies to tumor-type specific oncofetal antigens.

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.

Psychological effects of severe burn injuries.

Severe burn injuries provide researchers with an opportunity to study the effects of painful but usually transient trauma on psychological functioning. To that end, this article presents a review of the 3 main areas of this body of literature: (a) premorbid characteristics of people who sustain severe burn injuries, (b) psychological reactions during hospitalization, and (c) long-term adjustment. The general implications of these studies are discussed and then used to illuminate the circumstances under which individuals suffer the most from this type of trauma, the effects of such injuries on personality function, and how meaningful units of measurements can be defined. Potential clinical applications are also described.

"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.

Language changes and Alzheimer's disease: a literature review.

1. In Alzheimer's disease, the effect of cognitive changes on language and the ability to communicate and interact with others is profound. 2. Communication difficulties are a common problem identified by caregivers of demented individuals. Breakdown of communication can be frustrating and overwhelming for both patient and caregiver. 3. The deterioration of different linguistic features of language occurs at different rates, making it harder to identify deficits in the early phases of the disease. Mental status testing can give some objective measure of deficits. 4. Research is identifying explicit changes that occur in the language of Alzheimer's disease victims. Knowledge of these changes suggests strategies that can enhance communication.

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.

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.