Challenges in management of transient hyperinsulinism – a retrospective analysis of 36 severely affected children

Objectives Transient hyperinsulinism (THI) is a hypoglycemia disorder which resolves spontaneously within the first weeks or months of life. The pathomechanism of THI is not elucidated yet; however, it is known that perinatal stress predisposes for THI. We aimed to characterize the clinical phenotype and treatment of children with THI, and to identify options for improved management. Methods A retrospective analysis of 36 children with THI treated at the University Children’s Hospital Düsseldorf between 2007 and 2019 was performed. Results All children had risk factors for neonatal hypoglycemia or indicators of perinatal stress. Eighty three percent were diagnosed with hypoglycemia on day of life (DOL)1. None of the six diagnosed later had routine blood glucose screening and showed significantly lower blood glucose levels at the time of first blood glucose measurement compared to the children diagnosed on DOL1. Ninety seven percent of all children received intravenous glucose, 42% received continuous glucagon and 81% were started on diazoxide. Diazoxide withdrawal and subsequent fasting tests lacked standardization and were based on clinical experience. Three patients had a subsequent episode of hypoglycemia, after fasting studies only demonstrated “clinical” remission without proving the ability to ketogenesis. Conclusions Any kind of perinatal stress might pose a risk to develop THI, and postnatal monitoring for hypoglycemia still needs to be improved. Diazoxide is effective in children with THI; however, further studies are needed to guide the development of criteria and procedures for the initiation and discontinuation of treatment. Furthermore, establishing consensus diagnostic criteria/definitions for THI would improve comparability between studies.

Change in the Wind and Climate at the ExoMars 2022 Landing Site in Oxia Planum (Mars).

<p>The ESA/ROSCOSMOS ExoMars 2022 will land in Oxia Planum an area that shows outcrops of clay-rich Noachian-aged phyllosilicates overlaid by an Early Amazonian volcanic dark resistant unit (Adru) [1]. Using HiRISE images, we identified NE-SW (53.9 ± 13.2°) oriented TARs overlying an enigmatic ~EW (95.4 ± 10°) oriented ridge pattern that we interpreted as periodic bedrock ridges (PBRs) [2]. Ridges (~ 38 m spaced) display Y-junctions, show cross-cutting fractures and share the same blocky texture of the bedrock they are associated with. Ridge crestlines are locally found in continuity outside and inside heavily eroded impact craters around the dark upstanding material (Adru) exposed in the center of many craters. These stratigraphic relationships suggest that the ridges (PBRs) formed after the event(s) that eroded the crater rims and thus after deposition of the Adru (2.6 Ga). Ridges are even visible in association with impact crater ejecta and are superimposed by 10-25 m craters and boulders, so they pre-date these impact events. When associated with crater ejecta, ridges locally show two different crests. Both crests are truncated by craters suggesting they were emplaced before the impacts. We interpret this double crest arrangement as megaripples detaching from PBRs. The ejecta deposited over the megaripple-PBRs favored the preservation of the megaripple crests from a subsequent episode/s of erosion that led to the complete exposure of the PBRs on the plain. Because the preserved megaripples are locally visible on the southern edges of the PBRs, the wind that formed the megaripple-PBR system should have blown from N-NNE because the megaripples are located at the downwind side of PBRs [3]. To better understand the relative age of the ridges, we mapped their occurrence on 316 craters in the study area that we qualitatively classified as relatively degraded/old and pristine/young. Results show that ridges are only found in degraded/old craters but are never found inside pristine/young craters. Thus, the ridge forming process was only active in-between the formation of degraded/old and pristine/young craters. A major change in the wind regime occurred during or after the event that exposed the PBRs: N-NNE winds that shaped the PBRs changed into dominant SE winds that led to the deposition of the TARs above the PBR/megaripples. This work unveils a complex history of aeolian erosion and deposition in Oxia Planum during the Amazonian. By visiting PBRs for the first time, the ExoMars 2022 mission will provide further constraints on PBR formation and paleo-winds, shedding light on a past Amazonian environment.</p><p>This work is a summary of a manuscript that is currently in press on Geophysical Research Letters: Silvestro et al. 2021, Periodic Bedrock Ridges at the ExoMars 2022 Landing Site: Evidence for a Changing Wind Regime. DOI: 10.1029/2020GL091651.</p><p>[1] Quantin-Nataf C. et al. (2021). Astrobiology, 21, N.3.</p><p>[2] Silvestro S. et al. (2020). 6th Int. Planet. Dunes Work. 12-15 May, 2020. LPI No. 2188, id.3009.</p><p>[3] Hugenholtz C. H. et al. (2015). Aeolian Res. 18, 135–144.</p>

Solomon and Saturn I, 89 a, “prologa prim”: An Exercise in Monastic Reading Practice

This article reassesses the grammatically problematic half-line prologa prima (l. 89a) in the Old English wisdom poem Solomon and Saturn I, and suggests that it ought to be emended to the grammatically viable reading of “prologa prim”. Line 89 a introduces a passage in which the words of the Pater Noster become anthropomorphised as warriors and attack the devil. I will argue that “prologa prim” is an exegetical exercise, informed by grammatical theory and liturgical practice, designed for an audience of monastic readers. This multivalent half-line offers different levels of meaning when read according to different permutations of language and metaphor, in a process analogous to the interpretation of scripture according to the influential model of fourfold exegesis. When read literally, as ‘the first of the initial letters’, “prologa prim” indicates the unfolding and time-bound process of reading. Previous scholars (Anlezark 2009; Anderson 1998) have noted the allusive references in line 89 a to Greek logos (‘word’) and Old English prim (‘first hour’, ‘Prime office’), but not their full significance. Through these allusions, the reader shifts from a literal reading to a spiritual and metaphorical reading of the half-line, achieving a diachronic perspective of the Pater Noster’s recitation across time, and finally an atemporal perspective, reading in line 89 a a paraphrase of John 1:1, “In the beginning was the Word”. In conjunction with the subsequent episode of the battle, line 89 a forms an exemplum of the monastic practice of lectio divina. This example of ‘monastic poetics’ (O’Camb 2014; Niles 2019) moves from grammatical analysis to a vision of the Word.

High Rates of Recurrent Tuberculosis Disease: A Population-level Cohort Study

Background Retreatment tuberculosis (TB) disease is common in high-prevalence settings. The risk of repeated episodes of recurrent TB is unknown. We calculated the rate of recurrent TB per subsequent episode by matching individual treatment episodes over a period of 13 years. Methods All recorded TB episodes in Cape Town between 2003 and 2016 were matched by probabilistic linkage of personal identifiers. Among individuals with a first episode notified in Cape Town and who completed their prior treatment successfully we estimated the recurrence rate stratified by subsequent episode and HIV status. We adjusted person-time to background mortality by age, sex, and HIV status. Results A total of 292 915 TB episodes among 263 848 individuals were included. The rate of recurrent TB was 16.4 per 1000 person-years (95% CI, 16.2–16.6), and increased per subsequent episode (8.4-fold increase, from 14.6 to 122.7 per 1000 from episode 2 to 6, respectively). These increases were similar stratified by HIV status. Rates among HIV positives were higher than among HIV negatives for episodes 2 and 3 (2- and 1.5-fold higher, respectively), and the same thereafter. Conclusions TB recurrence rates were high and increased per subsequent episode, independent of HIV status. This suggests that HIV infection is insufficient to explain the high burden of recurrence; it is more likely due to a high annual risk of infection combined with an increased risk of infection or progression to disease associated with a previous TB episode. The very high recurrence rates would justify increased TB surveillance of patients with >1 episode.

Utility of rapid plasmin reagin titres in assessing treatment response and re-infection for infectious syphilis

Background The rapid plasma reagin (RPR) assay is commonly used as a surrogate marker of infectious syphilis, but is non-specific, slow to change and variable in its rate of decline post treatment. Methods: Within an urban sexual health service testing predominantly men who have sex with men, a file review of RPR changes was undertaken in all subjects who had a dilution level of ≥1:4, between January 2015 to the end of December 2018. Results: Overall, 248 cases of infectious syphilis were identified in 215 subjects (165 HIV seropositive, 50 HIV seronegative). Among unique-subject cases with follow-up RPR recorded, seroreversion to a non-reactive titre was achieved in only 42.3% (71/168) cases at a median of 235 days (interquartile range: 138–348 days) and was significantly less likely if patients had HIV infection (P = 0.02), late latent syphilis (P = 0.003) or a subsequent syphilis infection (P < 0.0001). Having HIV infection (P = 0.03) or a subsequent episode of syphilis (P = 0.01) were associated with a lower likelihood of documented cure. Conclusions: The slow decay in RPR titres post therapy and the inability of a significant number of subjects to achieve a non-reactive result over time makes RPR a poor test for assessing the adequacy of treatment or in diagnosing re-infection, especially in populations having repeated and frequent risk exposures. As the number of syphilis cases continue to climb, better tests that accurately assess pathogen presence are urgently needed.

Recurrent acute kidney injury: predictors and impact in a large population-based cohort

Background This study examined the impact of recurrent episodes of acute kidney injury (AKI) on patient outcomes. Methods The Welsh National electronic AKI reporting system was used to identify all cases of AKI in patients ≥18 years of age between April 2015 and September 2018. Patients were grouped according to the number of AKI episodes they experienced with each patient’s first episode described as their index episode. We compared the demography and patient outcomes of those patients with a single AKI episode with those patients with multiple AKI episodes. Analysis included 153 776 AKI episodes in 111 528 patients. Results Of those who experienced AKI and survived their index episode, 29.3% experienced a second episode, 9.9% a third episode and 4.0% experienced fourth or more episodes. Thirty-day mortality for those patients with multiple episodes of AKI was significantly higher than for those patients with a single episode (31.3% versus 24.9%, P < 0.001). Following a single episode, recovery to baseline renal function at 30 days was achieved in 83.6% of patients and was significantly higher than for patients who had repeated episodes (77.8%, P < 0.001). For surviving patients, non-recovery of renal function following any AKI episode was significantly associated with a higher probability of a further AKI episode (33.4% versus 41.0%, P < 0.001). Furthermore, with each episode of AKI the likelihood of a subsequent episode also increased (31.0% versus 43.2% versus 51.2% versus 51.7% following a first, second, third and fourth episode, P < 0.001 for all comparisons). Conclusions The results of this study provide an important contribution to the debate regarding the need for risk stratification for recurrent AKI. The data suggest that such a tool would be useful given the poor patient and renal outcomes associated with recurrent AKI episodes as highlighted by this study.

What is an admission? A standardised approach to classifying inpatient episode data from multiple jurisdictions

IntroductionInpatient datasets in the UK are primarily organised by episodes (periods of care under an individual consultant), while researchers often want to measure admissions (periods of stay in hospital). We developed a standardized method for identifying admissions in inpatient data, while accounting for differences between the four UK nations. Objectives and ApproachAll UK inpatient datasets include date variables, permitting chronological sequencing of episodes. They include flags describing whether an episode is a transfer of care, although structures and definitions differ. Data quality is variable leading to concurrent and overlapping episodes, duplication and “orphan” or “childless” transfer episodes, where no originating or destination episode can be identified. Our objective was to define a method for classifying individual episodes into a continuous period of stay in hospital, which would be consistently applicable to the analysis of inpatient datasets of all four UK nations, while prioritising clinical meaningfulness. Three permutations were considered. ResultsFor each permutation, episodes for an individual were linked when they related to the same individual and met the following criteria: Zero or one day gap between episode end and subsequent episode start Evidence of transfer according to admission method or discharge destination variables Episode overlapping or completely nested within another episode Permutations: a and b a only a and c Permutation three was adopted, as it was felt to be the most clinically meaningful approach, was not dependent on accurate recording of transfers and captured nested or overlapping episodes, which may occur for example when a patient is in a long-stay psychiatric or elderly care ward but requires care from a different specialty. Importantly it permitted consistent analysis of episodes across all UK nations. Conclusion/ImplicationsThe output of this work provides a useful guide for the classification of inpatient episodes into more clinically meaningful periods of care, and is applicable to the inpatient datasets of all four UK nations. It describes important issues to consider when classifying episodes of care, particularly relating to data quality.

Recurrent moderate hypoglycemia exacerbates oxidative damage and neuronal death leading to cognitive dysfunction after the hypoglycemic coma

Moderate recurrent hypoglycemia (RH) is frequent in Type 1 diabetes mellitus (TIDM) patients who are under intensive insulin therapy increasing the risk for severe hypoglycemia (SH). The consequences of RH are not well understood and its repercussions on neuronal damage and cognitive function after a subsequent episode of SH have been poorly investigated. In the current study, we have addressed this question and observed that previous RH during seven consecutive days exacerbated oxidative damage and neuronal death induced by a subsequent episode of SH accompanied by a short period of coma, in the parietal cortex, the striatum and mainly in the hippocampus. These changes correlated with a severe decrease in reduced glutathione content (GSH), and a significant spatial and contextual memory deficit. Administration of the antioxidant, N-acetyl-L-cysteine, (NAC) reduced neuronal death and prevented cognitive impairment. These results demonstrate that previous RH enhances brain vulnerability to acute hypoglycemia and suggests that this effect is mediated by the decline in the antioxidant defense and oxidative damage. The present results highlight the importance of an adequate control of moderate hypoglycemic episodes in TIDM.

Adherence and Persistence to Long-Acting Anticholinergics Treatment Episodes in Patients With Chronic Obstructive Pulmonary Disease

Background:No studies have examined adherence or persistence to long-acting anticholinergics (LAAC) treatment episodes in patients with chronic obstructive pulmonary disease (COPD). Objective: To estimate 1-year adherence and 5-year persistence to LAAC during treatment episodes, and the likelihood of initiating a subsequent treatment episode. Methods: A retrospective cohort of LAAC-treated COPD patients was reconstructed from Quebec databases. A treatment episode was initiated at cohort entry, defined as the first LAAC prescription date on/after the first COPD diagnosis date recorded between October 1, 2003, and March 31, 2014. We identified a subsequent treatment episode up to 5 years after the end of the episode initiated at cohort entry. We measured adherence as the proportion of days covered over 1 year. Persistence was defined as prescription renewal within 90 days of the previous prescription and was plotted using Kaplan-Meier curves over 5 years. The 5-year hazard and cumulative incidence of initiating a subsequent episode were estimated with survival analyses. We compared adherence and persistence between the treatment episodes using t and log-rank tests. Results: The cohort included 113 435 COPD patients. Adherence and persistence to LAAC were significantly lower in the subsequent treatment episode (55% vs 63%; P < 0.0001). The likelihood of initiating a subsequent episode was greatest immediately after the cessation of the initial episode, with 59% of patients starting a subsequent episode within 1 year. Conclusion: Adherence and persistence to LAAC were lower in the subsequent treatment episode. Interventions should be offered quickly after LAAC cessation.