Recent advances in the understanding of severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCARs) encompass a heterogeneous group of delayed hypersensitivity reactions, which are most frequently caused by drugs. Our understanding of several aspects of SCAR syndromes has evolved considerably over the last decade. This review explores evolving knowledge of the immunopathogenic mechanisms, pharmacogenomic associations, in vivo and ex vivo diagnostics for causality assessment, and medication cross-reactivity data related to SCAR syndromes. Given the rarity and severity of these diseases, multidisciplinary collaboration through large international, national and/or multicentre networks to collect prospective data on patients with SCAR syndromes should be prioritized. This will further enhance a systematized framework for translating epidemiological, clinical and immunopathogenetic advances into preventive efforts and improved outcomes for patients.

Piperacillin-tazobactam-induced linear IgA bullous dermatosis presenting clinically as Stevens-Johnson syndrome/toxic epidermal necrolysis overlap.

Linear IgA bullous dermatosis (LABD) is a subepidermal autoimmune bullous disease characterized by linear IgA deposition at the basement membrane zone, which is visualized by direct immunofluorescence. Patients with LABD typically present with widespread vesicles and bullae; however, this is not necessarily the case, as the clinical presentation of this disease is heterogeneous. LABD clinically presenting as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) is an infrequent, yet well-described phenomenon. Most cases of LABD are idiopathic, but some cases are drug-induced. Multiple drugs have been implicated in the development of LABD. We report a case of piperacillin-tazobactam-induced LABD presenting clinically as SJS/TEN overlap. This is the first reported case of a strong causal association between piperacillin-tazobactam and the development of LABD.

Diurnal blood pressure and urine production in acute spinal cord injury compared with controls.

STUDY DESIGN: This is a prospective observational study. OBJECTIVES: The objective of this study was to determine time-dependent changes in diurnal blood pressure (BP) and urine production in acute spinal cord injury (SCI). SETTING: This study was conducted in a specialist, state-based spinal cord service in Victoria, Australia. METHODS: Consenting patients admitted consecutively with acute SCI were compared with patients confined to bed rest while awaiting surgery and with mobilising able-bodied controls. Participants underwent ambulatory BP monitoring (ABPM), measurement of diurnal urine production and rated orthostatic symptoms over 1 year. Participants with night:day systolic BP (SBP) <90% were classified as dippers, 90-100% as non-dippers and >100% as reverse dippers. RESULTS: Participants comprised tetraplegics (n=47, 40.0±17.3 years), paraplegics (n=35, 34.4±13.9 years), immobilised (n=18, 30.9±11.3 years) and mobilising (n=44, 33.1±13.5 years) controls. At baseline, 24-h BP was significantly lower in tetraplegics (111.8±1.9/62.1±1.1 mm Hg) but not in paraplegics (116.7± 1.4/66.0±1.1 mm Hg), compared with controls (117.1 ±1.3/69.1±1.1 mm Hg), adjusting for gender. This difference was not observed at 1 year. The average night:day SBP in mobilising controls was 86.1±0.7%, differing from paraplegics (94.0±1.5%, P<0.001) and tetraplegics (101.5±1.5%, P<0.001). Urine production in tetraplegics and paraplegics did not fall at night compared with the day. Abnormal diurnal BP and orthostatic symptoms in tetraplegics persisted throughout the study. Nocturnal hypertension was observed in 27% (n=9) of tetraplegics, of whom only 2 had day hypertension. All mobilising controls with nocturnal hypertension (n=6, 14%) had day hypertension. CONCLUSION: People with SCI have a high prevalence of isolated nocturnal hypertension, reverse dipping, orthostatic intolerance and nocturnal polyuria. Cardiovascular risk management and assessment of orthostatic symptoms should include ABPM.

Non-HIV-associated Kaposi sarcoma in an immunosuppressed melanoma patient treated with dabrafenib.

WHAT IS KNOWN AND OBJECTIVE: Cutaneous toxicities are commonly seen with BRAF inhibitors, frequently involving painful hyperkeratosis of the feet. We illustrate an unexpected diagnosis of extensive bilateral pedal Kaposi sarcoma masquerading as BRAF inhibitor-related toxicity in a patient treated with dabrafenib for metastatic melanoma. CASE SUMMARY: A HIV-negative, non-diabetic, Italian man with a history of myasthenia gravis and metastatic melanoma presented with enlarging macular/plaque-like rash on his feet preceded by bilateral plantar shooting pains. The rash progressed in the context of acute-on-chronic immunosuppression and was initially thought due to commencement of the BRAF inhibitor (BRAFi) dabrafenib. Histopathological findings from skin biopsies revealed Kaposi sarcoma. The patient was continued on dabrafenib and received superficial radiotherapy to the feet with prompt relief of pain. WHAT IS NEW AND CONCLUSION: This case illustrates the diagnostic pitfalls in patients treated with targeted therapies and highlights the importance of broad differentials for unusual presentations and early biopsy.

A retrospective review of the ambulatory blood pressure patterns and diurnal urine production in subgroups of spinal cord injured patients.

STUDY DESIGN: Retrospective study. OBJECTIVES: To quantify diurnal blood pressure (BP) patterns and nocturnal hypertension and to measure diurnal urine production in spinal cord injury (SCI) patients with clinically significant disorders of BP control. SETTING: A specialist state-based spinal cord service in Victoria, Australia. METHODS: Medical records of patients with traumatic SCI who were referred to a specialist service for management of a BP disorder were examined. Ambulatory BP and nocturnal urine production were compared between groups of patients classified according to level, completeness and chronicity of SCI. Patients with night:day systolic BP <90% were classified as dippers, 90-100% as non-dippers and >100% as reversed dippers. RESULTS: Patients (44 tetraplegic, 10 paraplegic) were predominantly males (92.6%) aged 41±2.5 years (mean±s.e.m.). Referral was for orthostatic intolerance (n=37), autonomic dysreflexia (n=6), nocturnal polyuria (n=4), elevated BP (n=1) and peripheral oedema (n=1). The average BP was 111.1±1.4/65.0±1.2 mm Hg. In 56% of patients (n=30), BP at night was higher than during the day and another 37% (n=20) were non-dippers. Nocturnal hypertension was present in 31% (n=17) of the patients. In the tetraplegic patients, urine flow rate was greater during the night than day (121±9.5 ml h(-1) vs 89±8.2 ml h(-1), P=0.025). CONCLUSION: Ambulatory BP monitoring in patients with SCI and clinically significant BP disorders detected a high incidence of reversed dipping and nocturnal hypertension. We postulate elevated nocturnal BP may contribute to nocturnal diuresis that might cause relative volume depletion and thereby contribute to daytime orthostatic hypotension.

Improved Photocatalytic Performance of TiO2-Nitrogen-Doped Graphene Quantum Dot Composites Mediated by Heterogeneous Interactions.

Photocatalysis is typically monitored via analysis of phases in isolation and focuses on the removal of a target analyte from the solution phase. Here we analyze the photocatalytic action of a TiO2-nitrogen-doped graphene quantum dot (NGQD) composite on a target analyte, phenol, using comprehensive multiphase NMR (CMP-NMR) which observes signals in solid, solution, and gel phases in situ. Phenol preferentially interacts with the composite photocatalyst compared to pure TiO2, increasing its effective concentration near the catalyst surface and its degradation rate. The presence of NGQDs in the composite reduced the fouling of the catalyst surface and caused a reduction of photogenerated intermediates. Increased heterogeneous interactions, likely mediated by π-π interactions, are hypothesized to cause each of these improvements in the observed photocatalytic performance by TiO2-NGQDs. CMP-NMR allows the elucidation of how the photocatalytic mechanism is enhanced via material design and provides a foundation for the development of efficient photocatalysts.

Clinical and dermoscopic characteristics of Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy with a high mortality rate. Diagnosis is often delayed. OBJECTIVES: To characterize the dermoscopic features of MCC. METHODS: Clinical and dermoscopic images of 12 biopsy-proven MCCs were analysed in a retrospective manner, with existing dermoscopic criteria being scored independently by three dermatologists. RESULTS: The four most frequent clinical features were cherry red colour, shiny surface, sharp circumscription and nodular morphology. Significant dermoscopic features included linear irregular and polymorphous vessels, poorly focused vessels, milky pink areas, white areas, structureless areas and architectural disorder. Pigmented structures were absent from all lesions. CONCLUSIONS: The dermoscopic features described herein help the clinician to distinguish MCC from other benign and malignant red nodules. Increasing recognition of the presenting features will facilitate earlier diagnosis of MCC and reduced mortality.

Contamination of the central medical air supply with water leading to mass ventilator failure.

Here, we present a case of mass ventilator failure due to contaminated medical air. Multiple ventilators failed routine tests, including almost all of the ventilators in our intensive care unit. A faulty air compressor had led to water contamination of our centre's supply of medical air. Water entered the pipeline supply of air and, hence the ventilators and anaesthetic machines. The disruption of the machines' proportional mixer valve resulted in unreliable delivery of fresh gas flow. This malfunction was discovered during routine pre-use checks, and backup ventilators were available to replace the faulty ventilators. A shortage of equipment was averted due to a serendipitous availability of ventilator stockpiles prepared for the COVID-19 pandemic. Ventilator shortages are commonly described in mass casualty and pandemic scenarios. While there are multiple strategies described in literature to augment and maximise equipment available for mechanical ventilation, stockpiling equipment remains an expensive but necessary component of disaster contingency planning.

TiO2-NGQD composite photocatalysts with switchable photocurrent response.

A series of titanium dioxide-nitrogen doped graphene quantum dot (TiO2-NGQD) composite photocatalysts were synthesized through a simple hydrothermal reaction with varied NGQD content. Through a proposed Z-Scheme heterojunction, the composites were able to achieve increased photocurrent generation and photocatalytic degradation of phenol under both full spectrum and visible only illumination. The prepared composites were able to switch from anodic to cathodic photocurrent by changing the light source from full spectrum to visible wavelengths. The photocatalytic capabilities of the composites were tested by degrading phenol and this was monitored via nuclear magnetic resonance. All composites outperformed the commercial standard P25 TiO2 under both full spectrum and visible irradiation, with the 8 wt% NGQD composite showing a visible improvement of over 600% compared to P25. With the ability to manipulate the generation of majority charge carriers, TiO2-NGQDs have significant potential not only in photocatalysis, but in far reaching applications such as energy harvesting and water splitting.

Computer-assisted quantitative upper airway analysis following modified uvulopalatal flap and lateral pharyngoplasty for obstructive sleep apnoea: a prospective case-controlled study.

OBJECTIVES: The study aims to perform static and dynamic quantitative assessment of the anatomical changes of the upper airway before and after modified uvulopalatal flap and lateral pharyngoplasty and comparison of the improvement in airway dimensions, collapsibility and extent of normalisation to that of control patients. DESIGN: Prospective case-controlled study. SETTING: Computer-assisted quantitative measurement is used to compare upper airway parameters before and after modified uvulopalatal flap and lateral pharyngoplasty in patients with obstructive sleep apnoea (OSA). PARTICIPANTS: Patients with obstructive sleep apnoea diagnosed on sleep study and failed positive airway pressure therapy. MAIN OUTCOME MEASURES: Sleep study results, upper airway parameters and symptom score following surgery and its comparison to normal patients to assess the degree and extent of normalisation. RESULTS: Thirty-five study and 32 control subjects were recruited and completed the study. All the retropalatal airway dimensions like area, transverse diameter, longitudinal diameter and collapsibility showed statistically significant improvement following surgery. The success rate of this surgery is 43% (15 of 35) overall, 58% (14 of 24) for patients with isolated palatal obstruction and only 9% (1 of 11) for patients with multi-level obstruction. Comparing obstructive sleep apnoea to the control subjects, there are obvious and logical differences in their biostatistics, sleep study parameters and airway dimensions. The postoperative obstructive sleep apnoea retropalatal longitudinal diameter has a higher tendency of normalising to be comparable to those of control patients. CONCLUSIONS: Modified uvulopalatal flap and lateral pharyngoplasty is an effective surgical technique for the treatment of obstructive sleep apnoea. The surgery increases the resting retropalatal dimensions and reduces the retropalatal collapsibility.

Kikuchi-Fujimoto disease: a rare cause of histiocytic necrotising lymphadenitis in young ethnic women.

Kikuchi-Fujimoto is a rare but self-limiting disease usually affecting young ethnic females. The main clinical presentation is fever and cervical lymphadenopathy. Here we describe the cases of two patients with cervical lymphadenopathy, fever and fatigue. In addition, patients can present with neutropenia; hence, early diagnosis is crucial to exclude a malignant cause.

A new perspective on the photocatalytic action of titanium dioxide on phenol elucidated using comprehensive multiphase NMR.

Comprehensive Multiphase NMR (CMP-NMR) is a recently developed technique capable of simultaneously observing different phases - solutions, gels, and solids - while providing the chemical specificity of traditional NMR. With this new tool, the heterogeneous photocatalysis of phenol by titanium dioxide (P25 TiO2) is re-examined to gain information about the occurrence of reaction at different regions between the catalyst and the solution. It was found that the proportion of phenol in different phases changes over the course of the photodegradation period. The photocatalyst appears to preferentially degrade phenol molecules that are weakly associated with the surface, such that they have restricted mobility in a 'gel-like' state. Diffusion Ordered Spectroscopy (DOSY) corroborates the relative change in phenol signals between freely diffusing solution and diffusion restricted gels as measured using CMP-NMR. The surface of P25 TiO2 was found to foul over the course of the 200-hour photodegradation period that was monitored using the solid-state capabilities of the CMP-NMR. Finally, CMP-NMR showed differences in the photodegradation of phenol by P25 TiO2 to that of a TiO2-nitrogen doped graphene quantum dot (NGQD) composite. With the latter composite, no fouling of the surface was seen over time. This application of CMP-NMR to the field of catalysis demonstrates its potential to better understand and study photocatalytic systems in general.

Evolution of surgical modalities in the management of rhinophyma: our experience.

Rhinophyma is a progressive disease of the nose, which is characterised by skin thickening and sebaceous hyperplasia. Patients with rhinophyma are often stigmatised due to worsening disfigurement of their nose. This can also result in functional impairment such as reduced nasal patency. Severe cases of rhinophyma are best managed with varied surgical interventions, as there is no clear 'gold standard' treatment that has been described. We present our experiences in the management of rhinophyma and the evolution of treatment modalities that have been employed over a nine-year period.

An analysis of the continuing professional development needs of radiographers and radiation therapists in Singapore.

INTRODUCTION: Continuing Professional development (CPD) is deemed essential for the Radiographers (DR) and Radiation Therapists (RT) after Singapore commenced state registration. Diagnostic imaging and radiotherapy treatment services are constantly revolutionizing and those working in this field requires sufficient knowledge of the uptrends for training and development. The purpose of this survey is to identify the current training needs of the registered DR and RT in Singapore, and to understand their views about CPD activities. METHODS: An online questionnaire was disseminated by the Singapore Society of Radiographers (SSR) to all registered DR and RT in Singapore, and all practicing in restructured and private hospitals were included. Data collection took place from January 2018 to April 2018. RESULTS: 102 responses were analysed, where 89 were DR and 13 were RT. CPD was provided in 72.5% (n = 74) of the participants' institutions, and 69.6% (n = 71) of participants were aware of CPD. Interestingly, participants were significantly more likely to be unaware of CPD when working in an institution which do not offer CPD. Training programme objective was the most important factor for selecting a programme. 93.1% (n = 95) preferred SSR to support them for CPD. There were a few constraints to CPD engagements identified such as financial factors, lack of time, and institution availability. CONCLUSION: There was significant intrinsic motivation in a quality CPD activity. CPD activities should be current, accessible and relevant for the healthcare professionals to increase participation, which directly contributes to high standards of clinical care. IMPLICATIONS FOR PRACTICE: Local healthcare institutions should be aware and address needs, gaps and aspirations of the local DR and RT community to ensure adequate preparation has been made upon initiation of mandatory CPD.

Selective vulnerability to atrophy in sporadic Creutzfeldt-Jakob disease.

OBJECTIVE: Identification of brain regions susceptible to quantifiable atrophy in sporadic Creutzfeldt-Jakob disease (sCJD) should allow for improved understanding of disease pathophysiology and development of structural biomarkers that might be useful in future treatment trials. Although brain atrophy is not usually present by visual assessment of MRIs in sCJD, we assessed whether using voxel-based morphometry (VBM) can detect group-wise brain atrophy in sCJD. METHODS: 3T brain MRI data were analyzed with VBM in 22 sCJD participants and 26 age-matched controls. Analyses included relationships of regional brain volumes with major clinical variables and dichotomization of the cohort according to expected disease duration based on prion molecular classification (i.e., short-duration/Fast-progressors (MM1, MV1, and VV2) vs. long-duration/Slow-progressors (MV2, VV1, and MM2)). Structural equation modeling (SEM) was used to assess network-level interactions of atrophy between specific brain regions. RESULTS: sCJD showed selective atrophy in cortical and subcortical regions overlapping with all but one region of the default mode network (DMN) and the insulae, thalami, and right occipital lobe. SEM showed that the effective connectivity model fit in sCJD but not controls. The presence of visual hallucinations correlated with right fusiform, bilateral thalami, and medial orbitofrontal atrophy. Interestingly, brain atrophy was present in both Fast- and Slow-progressors. Worse cognition was associated with bilateral mesial frontal, insular, temporal pole, thalamus, and cerebellum atrophy. INTERPRETATION: Brain atrophy in sCJD preferentially affects specific cortical and subcortical regions, with an effective connectivity model showing strength and directionality between regions. Brain atrophy is present in Fast- and Slow-progressors, correlates with clinical findings, and is a potential biomarker in sCJD.

Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib.

BACKGROUND: Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. PATIENTS AND METHODS: We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. RESULTS: Among the 1232 lenvatinib-treated HCC patients, 453 (36.8%) were hepatitis C virus positive, 268 hepatitis B virus positive (21.8%), 236 nonalcoholic steatohepatitis (NASH) correlate (19.2%) and 275 had other etiologies (22.3%). The median progression-free survival (mPFS) was 6.2 months [95% confidence interval (CI) 5.9-6.7 months] and the median overall survival (mOS) was 15.8 months (95% CI 14.9-17.2 months). In the univariate analysis for OS NASH-HCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P = 0.0006]. In the univariate analysis for PFS NASH-HCC was associated with longer mPFS (7.5 versus 6.5 months; HR 0.84; 95% CI 0.71-0.99; P = 0.0436). The multivariate analysis confirmed NASH-HCC (HR 0.64; 95% CI 0.48-0.86; P = 0.0028) as an independent prognostic factor for OS, along with albumin-bilirubin (ALBI) grade, extrahepatic spread, neutrophil-to-lymphocyte ratio, portal vein thrombosis, Eastern Cooperative Oncology Group (ECOG) performance status and alpha-fetoprotein. An interaction test was performed between sorafenib and lenvatinib cohorts and the results highlighted the positive predictive role of NASH in favor of the lenvatinib arm (P = 0.0047). CONCLUSION: NASH has been identified as an independent prognostic factor in a large cohort of patients with advanced HCC treated with lenvatinib, thereby suggesting the role of the etiology in the selection of patients for tyrosine kinase treatment. If validated, this result could provide new insights useful to improve the management of these patients.

Direct evidence of the role of ATPγS in the binding of single-stranded binding protein (Escherichia coli) and RecA to single-stranded DNA.

To gain insight into the influence of ATPγS on the competitive binding of RecA and single-stranded binding protein (SSB) on single-stranded DNA (ssDNA), AFM imaging was used to examine the three-dimensional structures of the different complexes formed by the binding of the two proteins on ssDNA in the presence and absence of ATPγS. In the presence of ATPγS, RecA attaches to ssDNA, displacing SSB, to form continuous binding regions that caused considerable elongation of the strand. When ATPγS is absent, RecA could not compete with SSB and only binds at a few sites that correspond to the vacancy in ssDNA left when SSB unbinds. These results provide direct evidence that, while SSB binding affinity to DNA is substantially higher than that of RecA, the presence of ATPγS is sufficient to alter the events and enable RecA coating of DNA.

Orientational ordering of polymers by atomic force microscope tip-surface interaction.

Results of studies on the interaction between the tip of an atomic force microscope and polystyrene molecules in a film spread on a surface are reported. The tip produces a persistent deformation on the film; some of the polymer molecules are eventually pulled up by the tip. Nanometer-size structures are induced, resulting in a pattern that is periodic and is oriented perpendicular to the scan direction.

Combinatorial polyelectrolyte multilayer film fabrication.

A combinatorial strategy for the fabrication of a library of polyelectrolyte multilayer films is presented in this paper. This innovative approach involves the parallel formation of polyelectrolyte multilayer films in the individual wells of polystyrene microtitre plates under various deposition conditions. The progress of film formation was monitored via the intensity of the UV-vis absorbance of one of the depositing polyelectrolytes using a conventional microplate reader. We demonstrate the utility of this technique by building a library of 120 distinct polyelectrolyte multilayer films. Both the primer layer composition and salt content of the polyeletrolyte solutions were systematically varied in the preparation of films of nine bilayers. Film growth did not follow a linear adsorption regime for the first three bilayers regardless of the composition of the primer layer. We observed that increasing the sodium chloride concentration in the polyelectrolyte solutions resulted in increased polyelectrolyte absorption for all the conditions studied. The approach presented here is a convenient method of producing and characterizing multiple films rapidly and reproducibly, making it a valuable tool for optimizing film fabrication.