Rebalancing of the skin microbiome with an emollient 'plus' for effective management of atopic dermatitis: A mini review.

A balanced and diverse skin microbiome is pivotal for healthy skin. Dysregulation of the skin microbiome could disrupt the skin barrier function and result in the development of atopic dermatitis (AD), a common chronic and relapsing inflammatory skin disorder. Given the role that the skin microbiome plays in the initiation and maintenance of AD, maintaining a healthy skin microbiome is crucial for effective disease management. Specifically, current guidelines recommend emollients as the treatment mainstay in maintaining a functional skin barrier across disease severity. Emollient 'plus' or therapeutic moisturisers have recently emerged as the next-generation emollients that specifically aim to rebalance the skin microbiome and subsequently improve AD lesions. This article provides a quick overview of an emollient 'plus' or therapeutic moisturiser, discussing the clinical efficacy and tolerability of Lipikar Baume AP+M as a companion in AD management.

A prospective study of incidence and outcome of acute kidney injury among hospitalised patients in Malaysia (My-AKI).

INTRODUCTION: The incidence of acute kidney injury (AKI) among hospitalised patients has not been well studied in Malaysia. MATERIALS AND METHODS: We conducted a prospective, multicentre study in seven hospitals in West Malaysia. All the adults admitted in March 2017 fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI were included. RESULTS: Of the 34,204 patients screened, 2,457 developed AKI (7.18%), 13.1% of which occurred in intensive care unit (ICU). There were 60.2% males with a mean age of 57.8 (±17.5) years. The most common comorbidities were hypertension (55.0%), diabetes (46.6%), ischaemic heart disease (15.1%) and chronic kidney disease (12.0%). The commonest causes of AKI were sepsis (41.7%), pre-renal (24.2%) and cardiorenal syndrome (10.8%). Nephrotoxin exposure was reported in 31%. At diagnosis, the proportion of AKI stages 1, 2 and 3 were 79.1%, 9.7%, 11.2%, respectively. Referral to nephrologists was reported in 16.5%. Dialysis was required in 176 (7.2%) patients and 55.6% were performed in the ICU. Acidosis (46.2%), uraemia (31.6%) and electrolyte disturbance (11.1%) were the commonest indications. Continuous renal replacement therapy (CRRT) was required in 14%. The average length of hospital stay was 9.5 days. In-hospital mortality was 16.4%. Among survivors, full and partial renal recovery was seen in 74.7% and 16.4% respectively while 8.9% failed to recover. After a mean follow-up of 13.7 months, 593 (30.2%) of survivors died and 38 (1.9%) initiated chronic dialysis. Mortality was highest among those with malignancies (Hazard Ratio, HR 2.14), chronic liver disease (HR 2.13), neurological disease (HR 1.56) and cardiovascular disease (HR 1.17). CONCLUSION: AKI is common in hospitalised patients and is with associated high mortality during and after hospitalisation.

Changes in blood pressure after Messenger RNA COVID-19 vaccination.

The SARS-Cov-2 (COVID-19) vaccination began in Malaysia in March 2021 among frontliners and healthcare workers. Everyone at our hospital received the tozinameran (BNT162b2) Messenger RNA COVID-19 vaccine. Although hypertension has not been mentioned explicitly as an adverse event, concerns were raised after some healthcare staff observed an increase in their blood pressures. In response to that, the hospital began collecting vital signs during second-dose appointments. Vital signs were measured before, immediately after and 15-30 minutes postvaccination. We report our findings from the institution-wide effort to monitor changes in blood pressure among its staff and respond to any possible unwanted events.

Human Immunodeficiency Virus-infected men who have sex with men with syphilis: A 5-year multicentre study in Malaysia.

OBJECTIVES: High rates of syphilis have been reported worldwide among men who have sex with men (MSM). This study aims to describe the clinical pattern and treatment response of syphilis among human immunodeficiency virus (HIV)-infected MSM in Malaysia. METHODS: This is a retrospective study on all HIV-infected MSM with syphilis between 2011 and 2015. Data was collected from case notes in five centres namely Hospital Kuala Lumpur, Hospital Sultanah Bahiyah, Hospital Umum Sarawak, University of Malaya Medical Centre and Hospital Sungai Buloh. RESULTS: A total of 294 HIV seropositive MSM with the median age of 29 years (range 16-66) were confirmed to have syphilis. Nearly half (47.6%) were in the age group of 20-29 years. About a quarter (24.1%) was previously infected with syphilis. Eighty-three patients (28.2%) had other concomitant sexually transmitted infection with genital warts being the most frequently reported (17%). The number of patients with early and late syphilis in our cohort were almost equal. The median pre-treatment non-treponemal antibody titre (VDRL or RPR) for early syphilis (1:64) was significantly higher than for late syphilis (1:8) (p<0.0001). The median CD4 count and the number of patients with CD4 <200/µl in early syphilis were comparable to late syphilis. Nearly four-fifth (78.9%) received benzathine-penicillin only, 5.8% doxycycline, 1.4% Cpenicillin, 1% procaine penicillin, and 12.4% a combination of the above medications. About 44% received treatment and were lost to follow-up. Among those who completed 1 -year follow-up after treatment, 72.3% responded to treatment (serological non-reactive - 18.2%, four-fold drop in titre - 10.9%; serofast - 43.6%), 8.5% failed treatment and 17% had re-infection. Excluding those who were re-infected, lost to follow-up and died, the rates of treatment failure were 12.1% and 8.8% for early and late syphilis respectively (p=0.582). CONCLUSION: The most common stage of syphilis among MSM with HIV was latent syphilis. Overall, about 8.5% failed treatment at 1-year follow-up.

Syringocystadenoma papilliferum arising in a naevus sebaceous.

Naevus sebaceus is a cutaneous hamartoma with the potential of developing into benign or malignant neoplasms. Syringocystadenoma papilliferum (SCAP) have been reported to originate from naevus sebaceus. SCAP is a rare, benign adnexal skin tumour of apocrine or eccrine type of differentiation which typically presents as a nodule or a plaque on the scalp or face. We report a case of syringocystadenoma papilliferum arising in an undiagnosed pre-existing naevus sebaceus in a 56-year-old female.

Successful targeting of the NRG1 pathway indicates novel treatment strategy for metastatic cancer.

BACKGROUND: NRG1 fusion-positive lung cancers have emerged as potentially actionable events in lung cancer, but clinical support is currently limited and no evidence of efficacy of this approach in cancers beyond lung has been shown. PATIENTS AND METHODS: Here, we describe two patients with advanced cancers refractory to standard therapies. Patient 1 had lung adenocarcinoma and patient 2 cholangiocarcinoma. Whole-genome and transcriptome sequencing were carried out for these cases with select findings validated by fluorescence in situ hybridization. RESULTS: Both tumors were found to be positive for NRG1 gene fusions. In patient 1, an SDC4-NRG1 gene fusion was detected, similar gene fusions having been described in lung cancers previously. In patient 2, a novel ATP1B1-NRG1 gene fusion was detected. Cholangiocarcinoma is not a disease type in which NRG1 fusions had been described previously. Integrative genome analysis was used to assess the potential functional significance of the detected genomic events including the gene fusions, prioritizing therapeutic strategies targeting the HER-family of growth factor receptors. Both patients were treated with the pan HER-family kinase inhibitor afatinib and both displayed significant and durable response to treatment. Upon progression sites of disease were sequenced. The lack of obvious genomic events to describe the disease progression indicated that broad transcriptomic or epigenetic mechanisms could be attributed to the lack of prolonged response to afatinib. CONCLUSION: These observations lend further support to the use of pan HER-tyrosine kinase inhibitors for the treatment of NRG1 fusion-positive in both cancers of lung and hepatocellular origin and indicate more broadly that cancers found to be NRG1 fusion-positive may benefit from such a clinical approach regardless of their site of origin. CLINICAL TRIAL INFORMATION: Personalized Oncogenomics (POG) Program of British Columbia: Utilization of Genomic Analysis to Better Understand Tumour Heterogeneity and Evolution (NCT02155621).

Response to angiotensin blockade with irbesartan in a patient with metastatic colorectal cancer.

BACKGROUND: A patient suffering from metastatic colorectal cancer, treatment-related toxicity and resistance to standard chemotherapy and radiation was assessed as part of a personalized oncogenomics initiative to derive potential alternative therapeutic strategies. PATIENTS AND METHODS: Whole-genome and transcriptome sequencing was used to interrogate a metastatic tumor refractory to standard treatments of a patient with mismatch repair-deficient metastatic colorectal cancer. RESULTS: Integrative genomic analysis indicated overexpression of the AP-1 transcriptional complex suggesting experimental therapeutic rationales, including blockade of the renin-angiotensin system. This led to the repurposing of the angiotensin II receptor antagonist, irbesartan, as an anticancer therapy, resulting in the patient experiencing a dramatic and durable response. CONCLUSIONS: This case highlights the utility of comprehensive integrative genomic profiling and bioinformatics analysis to provide hypothetical rationales for personalized treatment options.

The Association Between Bullous Pemphigoid and Neurological Disorders in A Selected Malaysian Population.

BACKGROUND: An association of bullous pemphigoid with neurological disorders has been reported. The objectives of this study were to review the clinical characteristics of patients with bullous pemphigoid and compare the association between bullous pemphigoid and various neurological disorders and comorbidities. METHODS: This was a retrospective case-control study involving 43 patients with bullous pemphigoid and 43 age-, sex- and ethnicity-matched controls. RESULTS: There was a statistically significant association between bullous pemphigoid and neurological disorders [Odds Ratio (OR) = 3.5, 95% Confidence Interval (CI) 1.3 to 9.2, p=0.011 and adjusted OR=3.5, 95% CI 1.2-10.3, p=0.026], in particular for dementia (p=0.002). Although stroke was more common among patients with bullous pemphigoid, this association was not statistically significant with OR of 1.9 (95% CI 0.7 to 5.2) and adjusted OR of 2.1 (95% CI 0.6 to 7.2). Similarly both ischaemic stroke (OR 1.5, 95% CI 0.5 to 4.2) and haemorrhagic stroke (OR 1.5, 95% CI 0.2 to 9.7) were more common. Other neurological disorders more common among patients with bullous pemphigoid were Parkinson's disease and epilepsy. Dyslipidaemia was significantly less common among patients with bullous pemphigoid (OR 0.4, 95% CI 0.1 to 0.9, p=0.033). CONCLUSION: A combination of an inflammatory process, prothrombotic state and endothelial activation leads to an increased frequency of neurological disorders among patients with bullous pemphigoid. Thus, a holistic approach to patient care, including screening for dementia and control of comorbidities, should be practised as bullous pemphigoid affects more than just the skin.

Bilateral subtentorial empyema complicated with nosocomial acinectobacter ventriculitis: a case report.

Subtentorial subdural empyema is a rare and life threatening intracranial suppuration. It is usually an intracranial complication of otogenic infections. Early diagnosis and surgical drainage are the most important factors determining prognosis. The high mortality reported in the literature reflects the severity of subtentorial subdural empyema if proper management is delayed. Intracranial infections usually require between 4 to 6 weeks of intravenous antibiotics therapy. However, the prolonged duration of hospitalization as well as requirement for neurosurgically inserted indwelling devices may predispose these patients to new nosocomial infections.

Real-time polymerase chain reaction correlates well with clinical diagnosis of Clostridium difficile infection.

AIM: To determine the clinical utility of a rapid molecular assay for Clostridium difficile infection (CDI) in an acute hospital setting. METHODS: From March to September 2011, stool specimens from inpatients in two acute hospitals with suspected CDI were tested prospectively by routine cell culture cytotoxin neutralization assay (CCNA), real-time polymerase chain reaction (PCR) using the GeneXpert (Cepheid Inc., Sunnyvale, CA, USA), and a dual testing algorithm [glutamate dehydrogenase (GDH)/toxin enzyme immuno-assay, Premier, Launch Diagnostics, Longfield, UK]. All patients with positive PCR, CCNA or discrepant results were reviewed by a multi-disciplinary team (treating clinician, gastroenterologist, microbiologist and infection control nurse). RESULTS: C. difficile detection rates were 11.7% (PCR), 6% (CCNA) and 13.8% (GDH). Out of 1034 stool specimens included in the study, 974 (94.1%) had concordant CCNA and PCR results. Eighty-nine percent (886/985) had concordant CCNA, PCR and GDH results, and 94.4% (930/985) had concordant GDH and PCR results. Using clinical diagnosis as the reference, PCR had sensitivity of 99.1%, specificity of 98.9%, positive predictive value (PPV) of 91.9% and negative predictive value (NPV) of 99.9%. CCNA on a single sample had sensitivity of 51%, specificity of 99.4%, PPV of 91.9% and NPV of 94.3%. GDH had sensitivity of 83.8%, specificity of 94.5%, PPV of 64.7% and NPV of 97.9%. Almost twice as many patients were positive by PCR compared with CCNA (121 vs 62); 54/59 of those with discrepant results were clinically confirmed as CDI. CONCLUSION: Rapid diagnosis of CDI using PCR was timely, accurate and correlated well with clinical diagnosis.

A Randomised, Cross-Over, Placebo-Controlled Study of Aloe vera in Patients with Irritable Bowel Syndrome: Effects on Patient Quality of Life.

Background. Irritable bowel syndrome (IBS) is a chronic, difficult to treat condition. The efficacy of Aloe vera in treating IBS symptoms is not yet proven. The purpose of this study was to determine if Aloe vera is effective in improving quality of life. Methods. A multicentre, randomised, double-blind, cross-over placebo controlled study design. Patients were randomised to Aloe vera, wash-out, placebo or placebo, washout, Aloe vera. Each preparation (60 mL) was taken orally twice a day. Patient quality of life was measured using the Gastrointestinal Symptoms Rating Score, Irritable Bowel Syndrome Quality of Life, EuroQol and the Short-Form-12 at baseline and treatment periods 1 and 2. Results. A total of 110 patients were randomised, but only 47 completed all questionnaires and both study arms. Statistical analysis showed no difference between the placebo and Aloe vera treatment in quality of life. Discussion. This study was unable to show that Aloe vera was superior to placebo in improving quality of life. Drop outs and other confounding factors may have impacted on the power of the study to detect a clinically important difference. Conclusion. This study failed to find Aloe vera superior to placebo in improving quality of life proven Irritable Bowel Syndrome patients.

Comparison of microshear bond strengths of four self-etching bonding systems to enamel using two test methods.

BACKGROUND: Recent advances in enamel and dentine adhesive technology have resulted in the emergence of many new adhesive systems. Self-etching bonding systems do not require a separate etching step and the newest systems are the "all-in-one" systems which combine etching, priming and bonding into a single application. This study reports laboratory enamel microshear bond strengths of a self-etching priming and three all-in-one systems and also evaluates two different microshear bond test methods. METHODS: One hundred and nineteen enamel specimens were bonded (0.8 mm diameter) with either Clearfil Protect Bond (Kuraray), Xeno III (Dentsply), G Bond (GC) or One-Up Bond F (Tokuyama) using Palfique Estelite resin composite and stored in 37 degrees Celsius water for seven days. The microshear bond test method used either a blade or wire to apply the shear stress. Results were analysed with one-way ANOVA and post hoc (Tukey) multiple comparison analysis. RESULTS: Clearfil Protect Bond demonstrated higher and more consistent bond strengths than Xeno III, G Bond or One-Up Bond F. The wire method showed much greater reliability in results, with a coefficient of variation half that of the blade method. CONCLUSIONS: All-in-one adhesives seem to be less reliable than the two-step self-etching priming adhesive when bonding to enamel. Test method can significantly affect results in the microshear bond test method.

Prospective study of liver dysfunction in pregnancy in Southwest Wales.

BACKGROUND: Liver dysfunction in pregnancy has serious consequences. Its frequency and characteristics have not been systematically documented in Britain. We have prospectively determined incidence, causes, and outcome of liver dysfunction in pregnancy in an obstetric unit in Southwest Wales, UK. METHODS: A central laboratory identified all abnormal liver tests (bilirubin >25 micro mol/l, aspartate transaminase >40 U/l, or gamma glutamyl transpeptidase >35 U/l) from patients in antenatal clinics and wards of an obstetric unit serving a population of 250 000. Patients with abnormal liver tests were assessed and followed throughout and after pregnancy [corrected]. Medical advice was provided to obstetric teams. FINDINGS: There were 4377 deliveries during the 15 month study. A total of 142 patients had abnormal liver tests. There were 206 contributing diagnoses, the great majority being pregnancy specific. Among the most important were pre-eclampsia (68), HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome (30), obstetric cholestasis (23), hyperemesis gravidarum (11), acute fatty liver of pregnancy (five), and hepatic infarct (one). Sepsis, postoperative factors, and placental pathology (51) were not uncommonly responsible but incidental or pre-existing hepatobiliary disease was infrequent (17). Sixty five patients were delivered early by induction or caesarean section because of liver dysfunction. Despite substantial liver related morbidity, there were no maternal deaths and only two intrauterine deaths. CONCLUSIONS: Liver dysfunction was seen in 3% of deliveries during a 15 month prospective study and was usually directly related to pregnancy with spontaneous recovery in the puerperium. Incidence of the most serious conditions, acute fatty liver of pregnancy and HELLP syndrome, was much greater than previously reported. Profound effects on maternal and infant health were observed but close medical and obstetric collaboration ensured low mortality.

Enteric-release glyceryl trinitrate in active Crohn's disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Mucosal ischaemia may contribute to the pathogenesis of Crohn's disease. Microvascular abnormalities have been found in colonic resection specimens, and mucosal levels of constitutive nitric oxide synthase are reduced. AIM: To assess the efficacy of a novel, enteric-release formulation of the nitric oxide donor, glyceryl trinitrate, aimed at increasing the mucosal circulation and relaxing smooth muscle in the affected bowel. METHODS: The trial was randomized, double-blind and placebo-controlled. Baseline disease activity was assessed by a structured symptom diary, with blood tests and a quality of life assessment. Patients with a Crohn's disease activity index of > or = 150 and < 450 were randomized to receive 12 weeks of either glyceryl trinitrate (initially 6 mg twice daily, increasing to 9 mg twice daily after 6 weeks) or an identical placebo. Assessments were repeated at 6 and 12 weeks. RESULTS: Seventy patients (22 male) entered the study; 34 were given glyceryl trinitrate and 36 placebo. At 12 weeks, there were no differences between the treatment groups in terms of Crohn's disease activity index, pain, stool frequency, inflammatory markers or quality of life scores. CONCLUSIONS: Enteric-release glyceryl trinitrate did not benefit patients with mild to moderately active Crohn's disease. Whilst ischaemia may contribute to the pathogenesis of Crohn's disease, our results fail to provide supportive evidence for this hypothesis.

Scoring systems and risk assessment for upper gastrointestinal bleeding.

Mortality associated with acute upper gastrointestinal bleeding remains high despite advances in diagnosis and therapy. This was emphasized by the findings of the seminal English National Audit of acute gastrointestinal haemorrhage undertaken by Rockall and associates in the mid-1990s. The apparent lack of progress is largely due to less selective reporting in an ageing population with greater co-morbidity. Thus some deaths will be unavoidable even with exemplary treatment. Managing high risk patients in a dedicated area with close cooperation between medical and surgical gastroenterologists has been shown to improve outcome. The challenge is to select those patients who have most to gain from such a scarce and expensive resource so that their treatment can be optimized. Various risk factors have been identified to help achieve this end. Rockall's national audit data suggest that avoidable deaths remain a problem in most district general hospitals. A simple numerical score was derived from these audit data (Rockall score) to predict rebleeding and mortality. The score is based on five variables: age, shock, co-morbidity, endoscopic diagnosis and stigmata of recent haemorrhage. It has the advantage that pre-endoscopic assessment can be made by inexperienced medical or nursing staff. The system was validated internally in a second audit by Rockall and co-workers, and subsequent external validation has come from New Zealand and the Netherlands. The score is less reliable at predicting rebleeding than death and so is, as yet, an imperfect instrument. The scoring system has also proven valuable in selecting low risk patients for early discharge (resulting in health care economies) and for comparing outcome data from different hospitals or populations. Endoscopic treatment has recently been shown to reduce rebleeding rates and perhaps mortality. These advances in therapy are becoming more widely adopted and may influence the predictive ability of the Rockall score. The study from Edinburgh, in this issue, although small and with wide confidence intervals, supports the ability of the Rockall score to identify high risk cases amongst those given endoscopic treatment. It also suggests that an adjustment of the score may be required in these circumstances to prevent overcalling the risk of rebleeding and death.