Comparing the efficacy of different methods of faecal microbiota transplantation via oral capsule, oesophagogastroduodenoscopy, colonoscopy, or gastric tube.

BACKGROUND: The increasing prevalence of multidrug-resistant organism (MDRO) carriage poses major challenges to medicine as healthcare costs increase. Recently, faecal microbiota transplantation (FMT) has been discussed as a novel and effective method for decolonizing MDRO. AIM: To compare the efficacy of different FMT methods to optimize the success rate of decolonization in patients with MDRO carriage. METHODS: This prospective cohort study enrolled patients with MDRO carriages from 2018 to 2021. Patients underwent FMT via one of the following methods: oral capsule, oesophagogastroduodenoscopy (EGD), colonoscopy, or gastric tube. FINDINGS: A total of 57 patients underwent FMT for MDRO decolonization. The colonoscopy group required the shortest time for decolonization, whereas the EGD group required the longest (24.9 vs 190.4 days, P = 0.022). The decolonization rate in the oral capsule group was comparable to that in the EGD group (84.6% vs 85.7%, P = 0.730). An important clinical factor associated with decolonization failure was antibiotic use after FMT (odds ratio = 6.810, P = 0.008). All four groups showed reduced proportions of MDRO species in microbiome analysis after FMT. CONCLUSION: Compared to other conventional methods, the oral capsule is an effective FMT method for patients who can tolerate an oral diet. The discontinuation of antibiotics after FMT is a key factor in the success of decolonization.

Service evaluation of radiographer-led vetting and protocoling of Computed Tomography (CT) scan requests in a Singapore public healthcare institution.

INTRODUCTION: A service improvement project involving the vetting and protocoling of Computed Tomography (CT) scan requests by qualified CT radiographers was initiated in 2018. AIM: This study provides a comprehensive evaluation of how a radiographer-led initiative aims to ensure that the CT scan requests received by the Radiology department are clinically appropriate, which in turn will reduce interruptions to the interpretation and reporting of imaging examinations by radiologists, who might otherwise be required to attend to clinically inappropriate and wrongly protocolled CT scan requests. METHOD: Outpatient CT scan requests received from July to October 2021 were vetted and protocolled by a qualified CT-trained radiographer for parameters which included the appropriateness of the clinical indication, adequacy of patient preparation for the scan, as well as the suitability of the requested examination protocol pertaining to the need for contrast media, multiple contrast-enhanced imaging phases, and the appropriateness of the scan range. RESULTS: Poor patient preparation and insufficient or inaccurate clinical indications were the most common findings during the vetting process (71%). Out of the 64 CT scan requests with protocol errors, 77% were attributed to contrast media type errors. The odds of incorrect CT scan requests increased with the requesting clinician's rank, while there was no such significant correlation with the clinical specialty of the requesting clinician or the CT scan type. CONCLUSION: The meticulous vetting of imaging requests helps to ensure that limited imaging hardware resources are allocated to more clinically appropriate cases, correct protocols are applied to requested imaging scans, and that patients undergoing imaging are adequately prepared, thereby enhancing overall patient care. IMPLICATIONS FOR PRACTICE: Vetting of imaging requests by radiographers, who are capable to make appropriate clinical decisions related to their enhanced level of practice ensures patient safety and optimisation of Radiology resources.

Left ventricle geometry, atrial strain, ventricle strain, and hemodynamics across aortic valve before and after transcatheter aortic valve replacements.

INTRODUCTION: Transcatheter aortic valve replacements (TAVRs) has become widespread throughout the world. To date, there are no echocardiographic studies of TAVR patients from Southeast Asia (SEA). We sought to evaluate (1) changes in echocardiographic and strain values pre- and post-TAVR (2) relationship between aortic stenosis (AS) severity and strain values, (3) left ventricle geometry in severe AS, (4) relationship of flow rate to dimensionless index (DVI) and acceleration time (AT), and (5) effect of strains on the outcome. MATERIALS AND METHODS: Retrospective study of 112 TAVR patients in our centre from 2009 to 2020. The echocardiographic and strain images pre (within 1 month), post (day after), and 6 months post-TAVR were analyzed by expert echocardiographer. RESULTS: The ejection fraction (EF) increased at 6 months (53.02 ± 12.12% to 56.35 ± 9.00%) (p=0.044). Interventricular septal thickness in diastole (IVSd) decreased (1.27 ± 0.21 cm to 1.21 ± 0.23 cm) (p=0.038) and left ventricle internal dimension in diastole (LVIDd) decreased from 4.77 ± 0.64 cm to 4.49 ± 0.65 cm (p=0.001). No changes in stroke volume index (SVI pre vs 6 months p=0.187), but the flow rate increases (217.80 ± 57.61 mls/s to 251.94 ± 69.59 mls/s, p<0.001). Global longitudinal strain (GLS) improved from -11.44 ± 4.23% to -13.94 ± 3.72% (p<0.001), left atrial reservoir strain (Lar-S) increased from 17.44 ± 9.16% to 19.60 ± 8.77% (p=0.033). Eight patients (7.5%) had IVSd < 1.0 cm, and 4 patients (3.7%) had normal left ventricle (LV) geometry. There was linear relationship between IVSd and mean PG (r=0.208, p=0.031), between GLS to aortic valve area (AVA) and aortic valve area index (AVAi) (r = - 0.305, p=0.001 and r= - 0.316, p= 0.001). There was also relationship between AT (r=-0.20, p=0.04) and DVI (r=0.35, p<0.001) with flow rate. Patients who died late (after 6 months) had lower GLS at 6 months. (Alive; -13.94 ± 3.72% vs Died; -12.43 ± 4.19%, p=0.001). CONCLUSION: At 6 months, TAVR cause reverse remodelling of the LV with the reduction in IVSd, LVIDd, and improvement in GLS and LAr-S. There is a linear relationship between GLS and AVA and between IVSd and AVA.

Diastolic dysfunction grading, echocardiographic and electrocardiogram findings in 50 patients with apical hypertrophic cardiomyopathy.

INTRODUCTION: Apical Hypertrophic Cardiomyopathy (Apical HCM) is an uncommon variant of hypertrophic cardiomyopathy, but it is relatively more common in Asian countries. This is a retrospective, non-randomised, single centre study of patients with Apical HCM focusing on their diastolic dysfunction grading, echocardiographic parameters and electrocardiograms (ECG). METHODS: All Apical HCM patients coming for clinic visits at the Institut Jantung Negara from September 2017 to September 2018 were included. We assessed their echocardiography images, grade their diastolic function and reviewed their ECG on presentation. RESULTS: Fifty patient were included, 82% (n=41) were males and 18% (n=9) females. The diastolic function grading of 37 (74%) patients were able to be determined using the updated 2016 American Society of Echocardiography (ASE) diastolic guidelines. Fifty percent (n=25) had the typical ace-ofspades shape left ventricle (LV) appearance in diastole and 12% (n=6) had apical pouch. All patients had T inversion in the anterior leads of their ECG, and only 52% (n=26) fulfilled the ECG left ventricular hypertrophy (LVH) criteria. Majority of our patients presented with symptoms of chest pain (52%, n=26) and dyspnoea (42%, n=21). CONCLUSION: The updated 2016 ASE guideline makes it easier to evaluate LV diastolic function in most patients with Apical HCM. It also helps in elucidating the aetiology of dyspnoea, based on left atrial pressure. Clinicians should have a high index of suspicion for Apical HCM when faced with deep T inversion on ECG, in addition to a thick LV apex with an aceof- spades appearance during diastole.

Contralateral Approach to Coil Embolization of Proximal A1 Aneurysms Using the Anterior Communicating Artery.

BACKGROUND AND PURPOSE: Aneurysms arising from the proximal A1 segment of the anterior cerebral artery are rare, and their distinctive configurations often pose technical challenges during endovascular embolization. Herein, we present 11 patients with proximal A1 aneurysms requiring a contralateral approach (via the anterior communicating artery) to coil embolization. MATERIALS AND METHODS: From a prospectively collected data repository, we retrieved records of 11 patients consecutively treated for proximal A1 aneurysms between January 2011 and March 2018. In each instance, coil embolization was performed by the contralateral route. Outcomes were analyzed in terms of morphologic features and clinical status. RESULTS: Aneurysms in all 11 patients were directed posteriorly and were small (<5 mm). A contralateral approach (via the anterior communicating artery) was used after ipsilateral attempts at aneurysm selection failed in each instance, despite using a variety of microcatheters. Single punctures and single guiding catheters sufficed in 9 patients, but 2 patients required dual punctures and 2 guiding catheters. All endovascular treatments ultimately yielded excellent outcomes. Although 1 symptomatic infarct was manifested in the course of ipsilateral treatment, no morbidity or mortality resulted from the contralateral access. CONCLUSIONS: Due to angio-anatomic constraints, a contralateral strategy for coil embolization of proximal A1 aneurysms is acceptable if ipsilateral access is technically prohibitive and the vessels (contralateral A1 and anterior communicating artery) are amenable to the passage of microdevices.

Multimorbidity in bullous pemphigoid: a case-control analysis of bullous pemphigoid patients with age- and gender-matched controls.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the elderly and is associated with increased mortality. The extent of multimorbidity in patients with BP and its impact on survival are unclear. OBJECTIVES: To describe the extent and spectrum of multimorbidity in patients with BP and to ascertain its impact on survival. METHODOLOGY: This was a case-control study conducted in the setting of an academic medical centre. Cases defined as newly diagnosed BP patients referred to the inpatient dermatology service between 2005 and 2014. For every case, three age- and gender-matched controls were randomly selected. Retrospective review of medical records was performed. Univariate and multivariate comparisons of cases and controls were performed using conditional logistic regression. RESULTS: A total of 105 cases and 315 controls were included in this study. Eighty-eight cases (84%) were multimorbid (≥2 chronic diseases) as compared to 205 controls (65%) (P < 0.001), while the mean number of comorbid conditions was 3.2 ± 1.6 in cases compared to 2.4 ± 1.6 in controls (P < 0.001). 43% of cases had ≥4 comorbidities compared to 27% in controls (P = 0.003). On multivariate analysis (adjusting for age, gender and comorbidities), neurological disease (OR 10.93; CI: 5.74, 20.79) and hypertension (OR 2.38; CI: 1.18, 4.77) were positively associated with BP. Charlson comorbidity index was 6.0 ± 2.5 in cases compared to 5.0 ± 2.1 in controls (P = 0.002), and the 1-year mortality of cases and controls was 32.4% and 17.8%, respectively. CONCLUSION: Our study has shown that a significant proportion of patients with BP are multimorbid and individually have a higher number of comorbidities compared to matched controls. Disease burden and multimorbidity may well impact the prognosis of patients with BP.

Forebrain-specific ablation of phospholipase Cγ1 causes manic-like behavior.

Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1f/f; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca2+/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1f/f; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.

Detection of phenazepam in illicitly manufactured Erimin 5 tablets.

A validated ultra-high-performance liquid chromatographic (UHPLC) method was used to determine the phenazepam dosage in clandestinely produced Erimin 5 tablets. Tablets from five different seizures submitted to the laboratory in 2013 were found to have a dosage of about 2.4 milligrams. The measurement uncertainty of the assay was estimated to be 3.2 % (relative) at a coverage factor of k=2. As an adjunct study the dyes in the tablets from several seizures were determined by thin-layer chromatography (TLC) for future comparative studies.

Disseminated Hormographiella aspergillata infection with involvement of the lung, brain, and small intestine following allogeneic hematopoietic stem cell transplantation: case report and literature review.

Disseminated infection by Hormographiella aspergillata is extremely rare and small intestine involvement has not been reported previously. A 51-year-old man with myelodysplastic syndrome developed pneumonia after cord blood cell transplantation. Fungal growth from the biopsied lung was identified as H. aspergillata by morphology and the gene analysis. Although antifungal agents including voriconazole and liposomal amphotericin B were administered, he died of disseminated H. aspergillata infection. We review the literature and discuss the treatment and prognosis.

JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma.

Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.

Tenofovir-induced nephrotoxicity: A retrospective cohort study.

BACKGROUND: Tenofovir (TDF) has been associated with renal function deterioration, but local data regarding the incidence and risk factors for this adverse event were lacking. OBJECTIVES: To determine the incidence of nephrotoxicity in HIV-infected patients on tenofovir-based regimens and to evaluate risk factors involved in tenofovir-associated renal function decline. METHODS: This is a single-centre retrospective cohort study of 440 HIV-infected adults who were started on tenofovirbased antiretroviral regimens. Data were extracted from electronic medical and pharmacy records. RESULTS: A decline in eGFR of 25% or more was seen in 67 patients (15.2%) with an estimated incidence rate of 12 per 100 person-years. Among all 440 subjects, 22 discontinued TDF-based therapy due to renal complication. From multivariate analysis, the odds of developing >25% decrease in eGFR with tenofovir-containing regimen was three times higher for patients with baseline moderate renal impairment (HR 3.19; 95% CI, 1.43-7.12; p=0.005) and 14 times higher for patients with baseline severe renal impairment (HR 14.2; 95% CI, 11.20-170.7; p=0.036) as compared to those without pre-existing renal insufficiency. Age above 50 years and CD4 cell count of less than 50 were significantly associated with >25% decrement in eGFR. CONCLUSION: The incidence rate of tenofovir-related renal dysfunction was found to be 12 per 100 person-years. Preexisting renal impairment, age 50 and above, and CD4 cell count below 50 as were predictors for renal function decline. Given that the use of tenofovir is escalating in Malaysia, increased awareness about this adverse event is essential.

Effectiveness of antibacterial prophylaxis with non-absorbable polymyxin B compared to levofloxacin after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Fluoroquinolones are widely used for antibacterial prophylaxis during neutropenia following hematopoietic stem cell transplantation (HSCT). Nevertheless, data are inadequate as to whether fluoroquinolones decrease mortality rate compared with other antibiotics. METHODS: We retrospectively compared the efficacy of antibacterial prophylaxis using non-absorbable polymyxin B (PB) (n = 106) or systemic levofloxacin (LVFX) (n = 140) after allogeneic SCT at our institute between 2004 and 2013. RESULTS: No significant difference was observed between the 2 groups in the cumulative incidences of failure of prophylaxis (P = 0.21), clinically documented infections (P = 0.70), or non-relapse mortality within the first 100 days after transplantation (P = 0.42). With bacteremia, the rate of resistance to LVFX was 82% in the PB group and 100% in the LVFX group (P = 0.41). Also, no significant difference was found in overall survival between the 2 groups (P = 0.78). CONCLUSION: Our results indicate no difference in the effectiveness of antibacterial prophylaxis between systemic antibiotic LVFX and non-absorbable antibiotic PB.

[Features of the B chromosome in Korean wood mice Apodemus peninsulae (Thomas, 1906) from Transbaikalia and the Far East identified by the FISH method].

Korean field mice (Apodemus peninsulae) are widely distributed throughout northeastern Asia, including the Russian Far East, northern China, the Korean peninsula, Sakhalin, and Hokkaido. This mouse species is characterized by a high frequency of animals with B chromosomes differing in their number, morphology, and DNA composition in different geographical regions. For the first time a comparative analysis of DNA probes from B chromosomes with metaphase chromosomes of mice from Transbaikalia, the Far East (including the Russian Far East), Japan, and South Korea was conducted by in situ hybridization. B chromosomes in mice from the Russian Far East were shown to exhibit low variability in DNA content; however, the DNA composition of B chromosomes in species from Transbaikalia and Japan were highly variable. B chromosomes in A. peninsulae from the South Korean population demonstrate minor differences from those from the Russian Far East. We discuss the origin of B chromosomes in the studied region in comparison with previously obtained data for mice from Siberia and the Baikal region, as well as the dispersal routes of the Korean field mouse.

Clinical characteristics of responders to intravitreal bevacizumab in central serous chorioretinopathy patients.

PURPOSE: To investigate factors associated with good response to intravitreal bevacizumab (IVB) in central serous chorioretinopathy (CSC) patients. METHODS: We retrospectively reviewed 42 eyes of CSC patients of symptom duration more than 3 months who received a single or multiple successive IVBs on an as-needed basis (0.05 ml, 1.25 mg). High responders (HRs) were defined as complete resolution of subretinal fluid (SRF) on spectral domain optical coherence tomography (SD-OCT). Moderate responders (MRs) were defined as SRF resolution of 50-99% of pretreatment volume and poor responders (PRs) as SRF resolution <50%. Clinical, SD-OCT, fluorescein, and indocyanine green angiography findings were analyzed to find factors associated with HR. Descriptive statistics for all demographic and clinical variables were calculated, and comparisons were made using Wilcoxon's matched-pairs signed-rank test, the Mann-Whitney U-test for means with continuous data, Pearson's χ(2) test, and Fisher's exact test for categorical data. RESULTS: The mean number of IVB was 1.9. At postoperative 1 month, there were 10 (24%) HRs, 18 (43%) MRs, and 14 (33%) PRs. At the last follow-up (the mean 8.6 months), there were 25 HRs (60%), 9 MRs (21%), and 8 PRs (19%). Thicker subfoveal choroid (P=0.036), smaller lesion diameter (P=0.019), and better baseline best-corrected visual acuity (P=0.002) predicted HRs at postoperative 1 month. HR at the last follow-up was associated with classic pattern fluorescein angiography finding. CONCLUSIONS: Suboptimal effects of IVB on persistent CSC suggest primary IVB on selective cases with better vision, smaller lesion, and thicker choroid at baseline.

Pernicious anaemia presenting as hyperpigmentation.

An adult East Asian woman presented with sudden onset of hyperpigmented macules on her oral mucosal surfaces, palms and soles, in association with hypoguesia and loss of weight. This was found to be associated with underlying severe vitamin B12 deficiency secondary to pernicious anaemia.

Association between polymorphisms in period genes and bone density in postmenopausal Korean women.

OBJECTIVE: In the present study, we aimed to investigate the association between genetic polymorphisms in period (PER) genes and bone mineral density (BMD) in postmenopausal Korean women. METHODS: The PER1 c.2247C> T and c.2884C> G polymorphisms; the PER2 c.661G> A and c.3731G> A polymorphisms; the PER3 c.2592G> A, c.3029C> T, c.3035C> T, and c.3083T> C polymorphisms, and the 54 bp variable number tandem repeats polymorphism were analyzed in 551 postmenopausal Korean women. Serum leptin, soluble leptin receptor, osteoprotegerin, soluble receptor activator of the nuclear factor-κB ligand, and bone markers including bone alkaline phosphatase and carboxy-terminal telopeptide of type I collagen were measured, and the lumbar spine and femoral neck BMDs were also determined. RESULTS: The PER2 c.661G> A, PER3 c.3029C> T and c.3035C> T polymorphisms were not observed. The PER2 and PER3 polymorphisms evaluated were not related to BMD, whereas associations of the c.2247C> T and c.2884C> G polymorphisms in PER1 with the lumbar spine BMD were observed both singly and in combination. The CC haplotype homozygotes showed significantly lower lumbar spine BMD than participants with other genotypes. Additionally, 2.01-fold higher odds for osteoporosis of the lumbar spine were found in the CC haplotype homozygotes compared to women not carrying the haplotype CC allele. No significant differences in bone markers were detected according to the PER1 haplotype genotype. CONCLUSIONS: Our results suggest that both the PER1 c.2247C> T and c.2884C> G polymorphisms may be genetic factors affecting the lumbar spine BMD in postmenopausal Korean women.