Paracetamol overdose is common in developed countries but less than 10% involve large ingestions exceeding 30g or 500mg/kg. High dose acetylcysteine (NAC) has been proposed in patients taking large paracetamol overdoses based on reports of hepatotoxicity despite early initiation of NAC treatment with the commonly used 300 mg/kg intravenous acetylcysteine regimen. The evidence from cohorts of patients treated with the standard NAC regimen after large paracetamol overdoses shows that it is effective in most patients. Small studies in patients whose paracetamol concentration are above the 300mg/L nomogram line show that modification of the standard NAC regimen to provide a total of 400-500 mg/kg NAC over 21-22h may reduce the risk of hepatotoxicity (peak ALT>1000 IU/L) but the impact on development of hepatic failure, liver transplantation and mortality with this approach is presently unknown. Better risk stratification of patients taking paracetamol overdose may allow higher dose NAC and adjunctive treatments such as CYP2E1 inhibition and extracorporeal removal of paracetamol to be targeted to those patients at the highest risk of hepatotoxicity after a large paracetamol overdose.

Bone marrow necrosis (BMN) is a rare pathologic finding, but when encountered is most often associated with malignancy. In adults its presence correlates with an inferior prognosis, however in children the prognostic implication is unclear. We performed a retrospective review of 3,760 bone marrow specimens in patients ≤ 18 years over a ten-year period. BMN was identified in less than 1% of specimens and only in patients with leukemia, lymphoma or neuroblastoma. BMN contributed to a delay in diagnosis; however, advanced medical imaging may serve as a tool to localize non-necrotic areas for bone marrow sampling, facilitating an expedited diagnosis.

Cervical lymphadenopathy is a very common complaint for patients presenting to an endocrinology clinic. This case highlights common locations that malignancy presents at as well as their ultrasound characteristics.

Background: There remains limited knowledge about the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-COV2) vaccination in pediatric oncology patients, which is essential to provide counseling and risk adaptation in this vulnerable population. The goal of this study was to understand immunogenicity after vaccination in pediatric oncology patients and determine if certain clinical factors impacted response. Methods: Patients 0-25 years of age with a diagnosis of cancer and actively receiving therapy were enrolled on study. We excluded patients who were completely vaccinated prior to their cancer diagnosis. Blood samples were collected pre-vaccination, as well as 2, 4-6, and 8-12 weeks after vaccination. Healthy children who were fully vaccinated enrolled as controls. Clinical data and complete blood counts around time of vaccination were collected. To study B and T cell immunity, we measured neutralizing antibodies by enzyme-linked immunoassay and interferon gamma secretion by enzyme-linked immunospot, respectively. Results: 26 patients enrolled on study, for which 11 were evaluable oncology patients and 7 were healthy controls. Adequate B cell response was seen in 36.4% of patients and adequate T cell response in 77.8% of patients. Numbers were too small to detect differences based on malignancy type. There was no differences in immunity based on absolute lymphocyte count (ALC) or intensity of therapy. Conclusion: Pediatric oncology patients have a suboptimal immune response to SARS-COV2 vaccination. Booster doses will be imperative to provide optimal protection against COVID-19, however blood counts may not be a useful guide to optimize the time of administration.

Additional Features of Food Induced Immediate Reaction in the Esophagus (FIRE) in a Series of Adult Patients with Eosinophilic EsophagitisTo the EditorEosinophilic esophagitis (EoE) is a chronic disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil predominant inflammation. The predominant symptom in adults with active EoE is solid food dysphagia due to the high incidence of esophageal stricture formation. A quantitative tool has been developed to characterize the nature of these symptoms (1). Most typically patients complain of food going down slowly, food getting stuck and pain. These symptoms are most likely to occur during the passage of dense solid foods such as meats, bread and rice.Recently a phenomenon with a different symptom referred to as FIRE (food induced immediate reaction in the esophagus) has been described in adults with EoE. (2). Patients with eosinophilic esophagitis describe these esophageal symptoms as distinct from dysphagia. The symptoms typically occur after the food has been swallowed with rapid onset esophageal discomfort often described as tightening or pressure but without the sense of dysphagia. A large series of Swiss patients with eosinophilic esophagitis were queried via a form mailed to their homes or in clinics concerning symptoms related an immediate reaction in the esophagus distinct from dysphagia (2). A significant portion (49%) reported some form of esophageal discomfort related to eating. Although certain subject characteristics in this study such as younger age of onset of EoE and higher prevalence of allergies was noted, detailed clinical information on each subject was not available for review. Here in we described a series of patients with biopsy proven eosinophilic esophagitis who describe characteristic symptoms of FIRE following a specific food ingestion. For each selected FIRE patient a detailed chart review was conducted characterizing their demographics and EoE history (Table 1) as well as characteristics of their FIRE profile (Table 2). A number of features were noted in this group of 8 EoE patients as a previously unrecognized symptom complex. The onset of symptoms most often occurred within 1-60 minutes (median 3.5 minutes) after ingestion of the food. The duration of symptoms lasted from <10 minutes to > 6 hours (median 120 minutes). Among the patients the description of discomfort was often similar consisting of a tightening or pressure in the mid sternum. The most common foods inducing symptoms were beans, melon and beer. The symptoms were significant enough that patients attempted to subsequently avoid these foods. All patients were able to distinguish between symptoms related to their pollen food allergy syndrome and FIRE.The exact mechanism of this esophageal discomfort has not been elucidated. It appears distinct from pollen food allergy syndrome. It also appears different from EoE as uncommon foods such as banana, melon and avocado were capable of invoking symptoms, notably foods more commonly associated with oral allergy syndrome. However the strong association with atopy, the rapid onset of symptoms and symptoms distinct from dysphagia suggest a local possibly immunologic factor causing an immediate esophageal mucosal response. A careful history of FIRE symptoms should be part of the routine evaluation of patients with eosinophilic esophagitis. Further investigations will be required to help better understand the frequency and mechanism of this newly described phenomenon.Conflicts of InterestMH no conflicts, AS no conflictsMark Holbreich M.D.Alex Straumann M.D.1. Schoepfer AM, Straumann A, Panczak R, et al. Development and validation of a symptom-based activity index for adults with eosinophilic esophagitis. Gastroenterology 2014;147:1255–1266.2. Biedermann, L, Holbreich, M, Atkins, D, et al. Food‐induced immediate response of the esophagus—A newly identified syndrome in patients with eosinophilic esophagitis. Allergy . 2020; 00: 1– 9.Corresponding authorMark Holbreich M.D.Allergy and Asthma ConsultantsIndianapolis IN [email protected]

Idiopathic ventricular arrhythmias (VA) is defined as premature ventricular complexes (PVCs) or ventricular tachycardias (VT) that occur in the absence of structural heart disease. Endocardial radiofrequency (RF) ablation is often curative for idiopathic VA. The success of the procedure depends on the ability to localize the abnormal foci accurately. These arrhythmias typical originate from the right ventricular outflow tract (RVOT), specifically from the superior septal aspect, but can also originate from the left ventricular outflow tract (LVOT) and the coronary cusps.1 The QRS electrocardiogram (ECG) characteristics have been helpful in patients with VAs, patient with accessory pathways and patients who have pacemakers.2 VAs originating from the RVOT have typical ECG findings with a left bundle branch block (LBBB) morphology and an inferior axis.3In the current issue of the Journal of Cardiovascular Electrophysiology, Hisazaki et al. describe five patients with idiopathic VA suggestive of RVOT origin and who required ablation in the left-sided outflow tract (OT) in addition to the initial ablation in the RVOT for cure to be achieved. Patients exhibited monomorphic, LBBB QRS pattern with an inferior axis on ECG, consistent with the morphology of VAs originating from the RVOT. Interestingly, all patients had a common distinct ECG pattern: qs or rs (r ≤ 5 mm) pattern in lead I, Q wave ratio[aVL/aVR]>1, and dominant S-waves in leads V1 and V2. Mapping of the right ventricle demonstrated early local activation time during the VA in the posterior portion of the RVOT, matching the QRS morphology obtained during pacemapping. Despite RF energy delivery to the RV, the VAs recurred shortly after ablation in four patients and had no effect at all in one patient. A change in the QRS morphology was noted on the ECG that had never been observed before the procedure. The new patterns were suggestive of left-sided OT origin: the second VAs exhibited an increase in the Q wave ratio [aVL/aVR] and R wave amplitude in lead V1, decrease in the S wave amplitude in lead V1, and a counterclockwise rotation of the precordial R-wave transition. Early activation of the second VA could not be found in the RVOT, and the earliest activation time after mapping the LV was found to be relatively late. Real-time intracardiac echocardiography and 3D mapping systems were used to determine the location immediately contralateral to the initial ablation site in the RVOT. Energy was then delivered to that site which successfully eliminated the second VA. The authors postulated that the second VAs shared the same origins as the first VAs, and the change in QRS morphology is likely attributed to a change in the exit point or in the pathway from the origin to the exit point. The authors further explained that the VAs originated from an intramural area of the superior basal LV surrounded by the RVOT, LVOT and the transitional zone from the great cardiac vein to the anterior interventricular vein (GCV-AIV).A limitation of this study is that GCV-AIV ablation was not attempted; however, the authors’ approach is safer and was successful in eliminating VA. Another limitation is that left-sided OT mapping was not initially performed. Nevertheless, given the ECG characteristics, local activation time, and mapping, it was appropriate to attempt a RVOT site ablation.Overall, the authors should be commended for their effort to describe in detail patients with idiopathic VAs that required ablation in the left-sided OT following ablation in the RVOT. Although change in QRS morphology after ablation has been previously described, the authors were the first to describe the ECG patterns of these patients.4–7 The results of this study have important clinical implications. First, the authors have demonstrated the importance of anatomical approach from the left-sided OT for cure to be achieved. Second, insight into the location of the origin of the VA may be helpful to physicians managing patients with VAs from the RVOT. Finally, continuous monitoring of the ECG during ablation for a change in QRS morphology should be considered to identify patients who will require further ablation. We have summarized in Table 1 important ECG characteristics indicative VA of specific origins, based on the findings of this study and previous studies in the literature.3,8–15

We reported a case of a 14-months-old girl with erythematous and papulovesicular pink to red lesions on the face, the upper and the lower limbs. The history and the morphological features confirmed the dignosis of Gianotti Crosti syndrome.

A group of viruses, collectively known as Pteropine orthoreoviruses (PRVs), have recently been found in fruit bats and humans in Southeast Asia, Australia, and some African countries. This article intends to briefly discuss what is known about these viruses and their potential significance in public health and to advocate for increased surveillance of these zoonotic viruses to prevent potential future disease outbreaks, as well as to highlight a recent publication on this topic that was selected as an editor’s choice article in the Journal of Medical Virology 1.

Norway spruce is a conifer storing large amounts of terpenoids in resin ducts of various tissues. Parts of the terpenoids stored in needles can be emitted together with de novo synthesized terpenoids. Since previous studies provided hints on xylem transported terpenoids as a third emission source, we tested if terpenoids are transported in xylem sap of Norway spruce. We further aimed at understanding if they might contribute to terpenoid emission from needles. We determined terpenoid content and composition in xylem sap, needles, bark, wood and roots of field grown trees, as well as terpenoid emissions from needles. We found considerable amounts of terpenoids – mainly oxygenated compounds - in xylem sap. The terpenoid concentration in xylem sap was relatively low compared to the content in other tissues where terpenoids are stored in resin ducts. Importantly, the terpenoid composition in the xylem sap greatly differed from the composition in wood, bark or roots suggesting that an internal transport of terpenoids takes place at the sites of xylem loading. Our work gives hints that plant internal transport of terpenoids exists within conifers; studies on their functions should be a focus of future research.

The rapid expansion of impermeable surfaces in cities has a major impact on urban hydrology. Infiltration of rainwater is reduced and water runs off faster with higher runoff peaks. Urban trees as stormwater management tools are becoming more relevant to reduce flood risks in addition to other ecosystem services. An in-situ field experiment to measure throughfall on Norway maple ( Acer platanoides) and small-leaved lime ( Tilia cordata) was conducted to determine the interception of solitary urban trees with different degrees of surface sealing in the city of Freiburg, Germany. The relationships between rainfall characteristics, tree morphological traits, and the interception behavior were investigated with eight trees per species. 76 recorded rainfall events were evaluated from April to September 2021. Average interception values were higher for small-leaved lime (70.3 ± 6.6%) than for Norway maple (54.8 ± 10.3%) and hence much higher than in a typical forested environment. The average interception loss of all recorded events was 2.58 ± 0.60 mm for Norway maple and 3.73 ± 0.29 mm for small-leaved lime. For both tree species, significant linear correlations were found between the relative interception and other factors like rainfall depths, the leaf area index (LAI), and the plant area index (PAI) (adj.R 2 > 0.45). In contrast to Norway maple, small-leaved lime also showed significant relationships of several tree morphological parameters with the interception (adj.R 2 > 0.43). LAI, which also effects the interception, of both tree species significantly decreased with the degree of surface sealing. Our results provide a better understanding of the interception process of solitary trees for different urban sites and allows to parameterize interception based on measurable properties. However, further field experiments with various tree species need to be conducted to obtain a larger database for typical parameters in models and to support urban planners in managing stormwater runoff.

Aims To evaluate the effect of pre-RIRS ESWL on the efficiency and safety of RIRS in the treatment of proximal ureter stones. Methods The patients in the study population were divided into 2 groups. Group-1 was composed of patients who had undergone ESWL for proximal ureter stones before RIRS, and Group-2 was composed of patients who directly underwent RIRS without any prior ESWL. The clinical and demographic properties of the patients were analysed in the RIRSearch database. The operative outcomes, peroperative complications, postoperative complications, hospitalization time and the stone-free rates were compared between the groups. Results There were 56 patients in Group-1 and 95 patients in Group-2. The demographic and clinical properties were similar between the groups. The stone-free rates, peroperative complications and postoperative complications were also similar between the groups; however, the fluoroscopy time was significantly higher in Group-1 (p=.043). The cut-off duration of 10 weeks between ESWL and RIRS had reasonable/favourable discriminating ability, with a 51% sensitivity and 88% specificity rate for stone-free status. Conclusion Performing ESWL on the proximal ureter stones before RIRS did not change the efficacy and safety of RIRS. The time between the patient’s last ESWL session and RIRS had a predictive value for stone-free status, but did not have any effect on complications.

Edge disturbance can drive liana community changes and alter liana-tree interaction networks, with ramifications for forest functioning. Understanding edge effects on liana community structure and liana-tree interactions is therefore essential for forest management and conservation. We evaluated the response patterns of liana community structure and liana-tree interaction structure to forest edge in two moist semi-deciduous forests in Ghana (Asenanyo and Suhuma Forest Reserves: AFR and SFR, respectively). Liana community structure and liana-tree interactions were assessed in 24 50 × 50 m randomly located plots in three forest sites (edge, interior and deep-interior) established at 0–50 m, 200 m and 400 m from edge. Edge effects positively and negatively influenced liana diversity in forest edges of AFR and SFR, respectively. There was a positive influence of edge disturbance on liana abundance in both forests. We observed anti-nested structure in all the liana-tree networks in AFR, while no nestedness was observed in the networks in SFR. The networks in both forests were less connected, and thus more modular and specialised than their null models. Many liana and tree species were specialised, with specialisation tending to be symmetrical. The plant species played different roles in relation to modularity. Most of the species acted as peripherals (specialists), with only a few species having structural importance to the networks. The latter species group consisted of connectors (generalists) and hubs (highly connected generalists). Some of the species showed consistency in their roles across the sites, while the roles of other species changed. Generally, liana species co-occurred randomly on tree species in all the forest sites, except edge site in AFR where lianas showed positive co-occurrence. Our findings deepen our understanding of the response of liana communities and liana-tree interactions to forest edge disturbance, which are useful for managing forest edge.

INTRODUCTION:Ramsay-Hunt syndrome is a disease caused by reactivation of latent varicella zoster virus in the geniculate ganglia. It involves facial nerve paralysis and it is usually associated with a rash on the auricle and/or external ear [1]. Sometimes the blisters are not very noticeable and can be overlooked by the inspector. Other accompanying symptoms may be ache and fullness of the ear (78%), vertigo/dizziness (51%), hearing loss (45%), nausea, vomiting, tinnitus and hyperacusia [2].The diagnosis is mainly based on the history, clinical findings and neurological examination. Polymerase chain reaction assays may be useful by detecting DNA of the virus in exudates from ear scraping or cerebrospinal fluid (CSF) [3].It represents 7% of all peripheral facial paralysis and recovery rates are lower in this group [4,5]. Early treatment with a combination of acyclovir and prednisone is reported to be effective [6-8].

Conduction system pacing has brought abut a shift in the delivery of device therapy. Although gaining growing adoption, challenges remain; one of which is higher fluoroscopy times. Yang et al describe reducing and even aiming to eliminate fluoroscopy in left bundle area pacing implantation and replacing lead visualisation with transthoracic echocardiography. This editorial reviews these methods in context with recent developments in conduction system pacing and current literature.

We congratulate Kar et al. on their elegant study evaluating ex-vivo temperature profiles and the resulting thermal injury formation on the epiesophageal surface during radiofrequency (RF) ablation. In addition to being the first study to detail temperature profiles inclusive of the epiesophageal surface during RF ablation, we believe that the results add further concern to the use of temperature sensing technology in the quest to reduce esophageal injury. Three recent clinical trials have evaluated the efficacy of luminal esophageal temperature (LET) monitoring and found either no benefits, or signals of harm. On the other hand, two pilot RCTs suggest benefits of active cooling, and a large RCT, the IMPACT study, further confirms this benefit by finding an 83% reduction in esophageal lesion formation using an active cooling device. With no degradation in ablation efficacy, as well as a reduction/elimination of the need for fluoroscopy and reports of shortened procedure time with active cooling technology, the data of Kar et al., combined with growing clinical data, suggest that continued use of LET monitoring may be unjustified.

Objectives: The CF Foundation sponsored competitive awards for Mental Health Coordinators (MHCs) from 2016-2018 to implement the international guidelines for mental health screening and treatment in US CF centers. Longitudinal surveys evaluated success in implementing these guidelines using the Consolidated Framework for Implementation Research (CFIR). Methods: MHCs completed annual surveys assessing implementation from Preparation/Basic Implementation (e.g., using recommended screeners) to Full Implementation/Sustainability (e.g., providing evidence-based treatments). Points were assigned to questions through consensus, with higher scores assigned to more complex tasks. Linear regression and mixed effects models were used to: 1) examine differences in centers and MHC characteristics, 2) identify predictors of success, 3) model the longitudinal trajectory of implementation scores. Results: 122 MHCs (88.4% responded): Cohort 1 N=80, Cohort 2 N=30, Cohort 3 N=12. No differences in center characteristics were found. Significant improvements in implementation were observed across centers over time. Years of experience on a CF team was the only significant predictor of success; those with 1-5 years or longer reported the highest implementation scores. Change over time was predicted by >5 years of experience. Conclusions: Implementation of the mental health guidelines was highly successful over time. Funding for MHCs with dedicated time was critical. Longitudinal modeling indicated that CF centers with diverse characteristics could implement them, supported by evidence from the CF Patient Registry showing nearly universal uptake of mental health screening in the US. Years of experience predicted better implementation, suggesting that education and training of MHCs and retention of experienced providers are critical to success.

Aims of the study: To test the feasibility of a group psychosocial intervention called Learning Through Play (LTP) plus Culturally adapted Cognitive Behaviour Therapy (CaCBT) for depressed Kenyan mothers with children aged 0-36 months. Methods used to conduct the study: This study was a single-arm mixed methods feasibility study to test an integrated parenting intervention for maternal depression in a low-income rural area of Fumbini village in Kilifi District of Kenya. Women between the ages of 18 and 45 years with children up to three years were screened for depression using PHQ-9 (Patient Health Questionnaire). Those scoring above 10 on PHQ-9 were interviewed using the Revised Clinical Interview Schedule (CIS-R) to confirm the diagnosis of depression. Assessments were carried out at baseline and the end of the intervention (3 months), followed by qualitative interviews with 12 women. Qualitative interviews were analysed using thematic analysis from a social-constructionist theoretical lens. Results of the study: The LTP Plus was both feasible and acceptable with high satisfaction among the participants. Qualitative results showed that the women perceived the intervention as beneficial in reducing the symptoms of depression, coping with stress and negative emotions. The results also indicated that there was a reduction in scores on PHQ-9, GAD-7 with an increase in perceived social support, health-related quality of life and an improvement in mothers’ knowledge about child development at the end of the intervention. Conclusions drawn from the study and clinical implications: This study represents the first feasibility research on integrated parenting intervention in Kenya. The results indicated that culturally adapted LTP plus CaCBT is feasible and acceptable in a low-income setting of Kenya. There is now a need to study the clinical and cost-effectiveness of LTP plus CaCBT in an appropriately powered larger randomised control trial, with a longer follow-up period.

Cough is an adverse effect that may hinder the delivery of drugs into the lungs. Chemical or mechanical stimulants activate the transient receptor potential in some airway afferent nerves (C or A fibres) to trigger cough. Types of inhaler device and drug, dose, excipients, formulation characteristics including pH, tonicity, aerosol output and particle size may trigger cough by stimulating the cough receptors. Release of inflammatory mediators may increase the sensitivity of the cough receptors to stimulants. The cough-provoking effect of aerosols is enhanced by bronchoconstriction in diseased airways and reduces drug deposition in the target pulmonary regions. In this article, we review the factors by which inhalation products may cause cough.