Adeno-Associated Virus 2 and Human Adenovirus F41 in Wastewater during Outbreak of Severe Acute Hepatitis in Children, Ireland.

During April-July 2022, outbreaks of severe acute hepatitis of unknown etiology (SAHUE) were reported in 35 countries. Five percent of cases required liver transplantation, and 22 patients died. Viral metagenomic studies of clinical samples from SAHUE cases showed a correlation with human adenovirus F type 41 (HAdV-F41) and adeno-associated virus type 2 (AAV2). To explore the association between those DNA viruses and SAHUE in children in Ireland, we quantified HAdV-F41 and AAV2 in samples collected from a wastewater treatment plant serving 40% of Ireland's population. We noted a high correlation between HAdV-F41 and AAV2 circulation in the community and SAHUE clinical cases. Next-generation sequencing of the adenovirus hexon in wastewater demonstrated HAdV-F41 was the predominant HAdV type circulating. Our environmental analysis showed increased HAdV-F41 and AAV2 prevalence in the community during the SAHUE outbreak. Our findings highlight how wastewater sampling could aid in surveillance for respiratory adenovirus species.

Silicon Photomultiplier-A High Dynamic Range, High Sensitivity Sensor for Bio-Photonics Applications.

This work is an overview of silicon photomultipliers (SiPMs) with a view to defining their importance for bio-photonic and clinical applications. SiPMs are benchmarked against other common photodetectors, namely, PIN diodes and avalanche photodetectors (APDs) and are compared with respect to important circuit design parameters. It will be shown that careful selection of the design bias voltage, overvoltage, gain defining components and device integration to micro-optics can allow SiPM detectors to achieve considerable sensitivity for auto-fluorescence (AF) detection and a wide dynamic range at low optical powers (~1 pW to ~4 µW). The SiPM has a manageable bias voltage (~25 V to ~30 V DC) for systems integration, and with optimised sensitivity it will enhance bio-photonic research in the area of AF to detect intraoperatively, for example, brain tumour margins.

Standardised computed tomographic assessment of left atrial morphology and tissue thickness in humans.

AIMS: Left atrial (LA) remodelling is a common feature of many cardiovascular pathologies and is a sensitive marker of adverse cardiovascular outcomes. The aim of this study was to establish normal ranges for LA parameters derived from coronary computed tomographic angiography (CCTA) imaging using a standardised image processing pipeline to establish normal ranges in a previously described cohort. METHODS: CCTA imaging from 193 subjects recruited to the Budapest GLOBAL twin study was analysed. Indexed LA cavity volume (LACVi), LA surface area (LASAi), wall thickness and LA tissue volume (LATVi) were calculated. Wall thickness maps were combined into an atlas. Indexed LA parameters were compared with clinical variables to identify early markers of pathological remodelling. RESULTS: LACVi is similar between sexes (31 ml/m2 v 30 ml/m2) and increased in hypertension (33 ml/m2 v 29 ml/m2, p = 0.009). LASAi is greater in females than males (47.8 ml/m2 v 45.8 ml/m2 male, p = 0.031). Median LAWT was 1.45 mm. LAWT was lowest at the inferior portion of the posterior LA wall (1.14 mm) and greatest in the septum (median = 2.0 mm) (p < 0.001). Conditions known to predispose to the development of AF were not associated with differences in tissue thickness. CONCLUSIONS: The reported LACVi, LASAi, LATVi and tissue thickness derived from CCTA may serve as reference values for this age group and clinical characteristics for future studies. Increased LASAi in females in the absence of differences in LACVi or LATVi may indicate differential LA shape changes between the sexes. AF predisposing conditions, other than sex, were not associated with detectable changes in LAWT.Clinical trial registration:http://www.ClinicalTrials.gov/NCT01738828.

A Surviving Case of Acanthamoeba Granulomatous Amebic Encephalitis in a Hematopoietic Stem Cell Transplant Recipient.

BACKGROUND Acanthamoeba are free-living amoebae with potential to infect immunocompromised hosts. The mortality rate of granulomatous amebic encephalitis (GAE) due to Acanthamoeba exceeds 90% and there are currently no reports of survival of this infection in recipients of hematopoietic stem cell transplant. CASE REPORT We report herein the case of a 32-year-old man presenting to our service with abrupt neurological deterioration and seizures 5 months after allogeneic stem cell transplantation for Hodgkin lymphoma. Clinical and imaging findings were non-specific at presentation. Multiple circumscribed, heterogenous, mass-like lesions were identified on MRI. Brain biopsy was performed and revealed multiple cysts and trophozoites suggesting a diagnosis of granulomatous amebic encephalitis. PCR testing confirmed Acanthamoeba. Treatment with miltefosine, metronidazole, azithromycin, fluconazole, pentamidine isethionate, and co-trimoxazole was instituted and the patient survived and shows continued improvement with intensive rehabilitation. CONCLUSIONS We report the first successful outcome in this setting. The diagnosis would have been missed on cerebrospinal fluid analysis alone, but was rapidly made by histological analysis of brain biopsy. This diagnostically challenging infection is likely under-recognized. Early brain biopsy and commencement of a prolonged miltefosine-containing anti-ameba regimen can be curative.

Sacubitril-Valsartan in a routine community population: attention to volume status critical to achieving target dose.

AIMS: In the PARADIGM-heart failure trial, sacubitril-valsartan demonstrated a reduction in heart failure admissions and reduced all-cause mortality in patients with heart failure with reduced ejection fraction. Although real world data have shown similar benefits regarding efficacy and safety, there has been difficulty in achieving the target dose (TD). The factors preventing the achievement of TD remains unclear. This study assesses the tolerability, ability to achieve, and factors linked to attaining TD in a routine clinical population. METHODS AND RESULTS: This is a retrospective single-centre review of patients switched from angiotensin-converting enzyme inhibitors/angiotensin receptor blockers to sacubitril-valsartan between May 2016 and August 2018. Baseline and follow-up clinical characteristics and biomarker profiles were collected. Univariate and multivariate analyses were used to analyse predictors of achieving TD. Clinical response to sacubitril-valsartan was defined as a reduction in N terminal pro BNP of ≥30%, or an increase in left ventricular ejection fraction of ≥5% compared with baseline values. To date, a total of 322 patients (75% male patients) have been switched to sacubitril-valsartan. Those still in the titration phase were excluded (n = 25). Sacubitril-valsartan was not tolerated in 40 patients (12.4%). Those intolerant were older (73.4 years [68.3, 80.6] vs. 69.1 years [61.2, 76]; P = 0.003) and had worse renal function with estimated glomerular filtration rate (53.5 mL/min/1.72 m2 [36.8, 60.2] vs 60 mL/min/1.72 m2 [47, 77]; P ≤ 0.001). Of the remaining 257 patients, TD (97/103 mg BD) was achieved in 194 patients (75.5%), while 37 patients (11.4%) were maintained on 49/51 mg BD and 26 patients (8.1%) remained on 24/26 mg BD. Symptomatic hypotension (74.6%) was the main impediment to attaining TD, followed by renal deterioration (12.7%), and to a lesser extent hyperkalaemia and gastrointestinal symptoms (4.8% each). Diuretic dose decrease was achieved in 37.2% of patients, and this was the strongest independent predictor of achieving TD (odds ratio = 2.1; 95% confidence interval [1.16, 3.8]; P = 0.014). Responder status by N terminal pro BNP criterion was observed in 99 of 214 patients (46.3%) while 70 of 142 (49.3%) attained the left ventricular ejection fraction response status. Achieving this response was independently linked to achieving TD. CONCLUSIONS: Sacubitril-valsartan was well tolerated. Achievement of TD was possible in the majority of the cohort and was linked to response metrics. Reduction in diuretic was required in a large percentage of the population and was the strongest predictor of attaining TD. Therefore, careful clinical attention to volume status assessment is essential to maximising the benefits of sacubitril-valsartan.

Principles of medical ethics in supportive care: a reflection.

The possibility of medical-moral controversy in contemporary health care delivery is occasioned by the interfacing of expanding technology with both professional and personal value systems, frequent and significant knowledge deficits on the part of health care consumers, and increased circumspection of and economic constraints experienced by health care providers. Particularly in an era of increasing regulatory mandates and the frequent and lamentable decrease in the availability of human, natural, and institutional resources, an understanding of the function of ethical analysis is indigenous to care, which is simultaneously medically appropriate and morally indicated. But while a familiarity with and an appreciation of the potential contribution of ethical reasoning is essential in all health care delivery, it assumes critical importance in supportive care. In that venue, where the rigors and demands of aggressively therapeutic interventions have ceased and the goal and the demeanor of care have shifted to the palliative mode, heightened attention to the principles of medical ethics is necessary for the balancing of rights and responsibilities for health care consumers and providers alike. This issue ultimately can be singularly salient in providing care that is patient centered and directed. Individuals acting as moral agents, suggesting what "ought" to be done in a given situation, either for themselves or as they are involved in rendering or supporting decisions proffered for or by other moral agents, particularly those in extremis, those in the throes of terminal illness following the collapse of the curative mode, need recourse to principles to facilitate their reasoning. Although the employment of each principle of medical ethics offers guidelines for reflection on the most comprehensive and appropriate care, it is attention to autonomy, informed consent, and beneficence that promotes the most effective supportive care. For even as the question of medical viability is settled in favor of palliation over aggression, there remain the entanglements of psychological stability, conflicting value systems, and the impact of the social milieu as well as the issues of economic responsibility and resource accountability. It is in the attention to the medical ethical principles of autonomy and informed consent, especially as amplified by the creation of and respect for advance directives, that the most holistic and productive supportive care can be offered. It is also in this posture that appeal to the principle of beneficence is made. Just as the progress of disease and, therefore, the realistic goals of care change, so too can an individual's considered opinion with regard to end-of-life decisions. Preserving the integrity of patients and caregivers alike and engaging in fruitful and informative dialog prior to seeking volitional authorization or operationalizing a supportive approach demonstrates renewed concern for both patient autonomy and professional accountability in the provision of a comprehensive end-of-life care plan. Discussions will not be avoided until they can no longer effectively take place, salient questions will not go unanswered, and decisions around end-of-life questions, in the mode of supportive care, will not be absent where care was exercised to engage patients in significant dialog earlier rather than later in their disease processes.