A Case Report: The First Show Phenomenon In The Treatment Of Spinal Cord Injury With Regentime Procedure Using Autologous Bone Marrow-Derived Stem CellsRita T. Boulos a†, Lea I. Nemerb†, Vanessa J. Mansour c†, Cynthia F. Najjoumd††,Elsa A. Asmar e†† and Nassim H. Abi Chahinef*† Authors’ equal contribution†† Authors’ equal contributionStem Cell Transplantation/Neurology, ACE Cells Lab Limited, Beirut, LBStem Cell Transplantation/Molecular Biology, ACE Cells Lab Limited, Beirut, LBStem Cell Transplantation/Infectious Diseases/Immunology, ACE Cells Lab Limited, Beirut, LBStem Cell Transplantation/Infectious Diseases/Immunology, ACE Cells Lab Limited, Beirut, LBStem Cell Transplantation/Functional Genomics/Proteomics, ACE Cells Lab Limited, Beirut, LBStem Cell Transplantation/Neurological Surgery, ACE Cells Lab Limited, Beirut, LB* Correspondence to:Dr. Nassim H. Abi ChahineTel: +9613082498E-mail: [email protected]

Stroke in Sickle Cell Revascularization Surgery Retrospective Study (SiSCRS) in this issue reports retrospective data from 15 medical centers to examine the benefit of cerebral revascularization surgery (CRS) in children with sickle cell disease (SCD) who also have Moyamoya Syndrome (SCD-MMS). The American Society of Hematology guidelines “suggests evaluation for revascularization surgery in addition to regular blood transfusion” for treating SCD-MMS combined with a history of stroke or transient ischemic attack but categorizes this as a “conditional recommendation based on very low certainty in the evidence about effects”. The research presented in this article is aimed at reducing the uncertainty surrounding revascularization surgery as a treatment using retrospective data from 15 medical centers with expertise in CRS for SCD-MMS. Even with the 78 children with CRS (Surgery group) and 63 children in the non-surgery (Conservative group), the differences between the two groups had mixed statistical significance in multivariate analyses. SiSCRS is an important retrospective analysis but must be interpreted with caution. The benefit of CRS attains statistical significance only in some of the comparisons. The rate of stroke in pediatric SCD decreases with age, creating a bias in favor of the older group (i.e., the Surgery Group) to have fewer CVEs, The additional role of aspirin and the bias of patient selection for surgery also weaken the ability to make definitive statements. The SiSCRS results suggest a likely retrospective benefit of CRS, but the benefit must be demonstrated with more rigorous studies in the future.

Whole bowel irrigation is a method of gastric decontamination in the poisoned patient involving administration of large volumes of osmotically balanced polyethylene glycol-electrolyte solution to empty the gastrointestinal tract of ingested toxins before absorption, limiting systemic toxicity. While this approach may seem intuitive and it can lead to expulsion of tablets or packets in the rectal effluent, there is a lack of evidence correlating this with improved patient outcomes. Administration of whole bowel irrigation is also challenging to the inexperienced physician and associated with adverse effects, which may be serious. Recommendations for the consideration of whole bowel irrigation are limited to patients who have ingested modified release preparations, those of have ingested pharmaceuticals not adsorbed by activated charcoal, and for the removal of packages in body packers. Until more robust evidence is available from high-quality prospective studies demonstrating efficacy, the use of whole bowel irrigation should not be used routinely in poisoned patients.

Long-term prognosis after low-dose peanut challenge for patients with history of anaphylaxisNobuko Akamatsu, MD, PhD1,2, Ken-ichi Nagakura, MD, PhD1, Sakura Sato, MD3, Noriyuki Yanagida, MD, PhD1,3,*, Motohiro Ebisawa, MD, PhD3 1Department of Pediatrics, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan2Department of Pediatrics and Adolescent Medicine, Tokyo Medical University Hospital, Tokyo, Japan3Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, JapanRunning title: Prognosis after low-dose peanut challenge*Corresponding author: Noriyuki Yanagida, MD, PhDDepartment of Pediatrics, National Hospital Organization, Sagamihara National Hospital,18-1, Sakuradai, Minami-ku, Sagamihara, Kanagawa 252-0392, JapanE-mail: [email protected] count: 1190Number of figures: 2 Number of tables: 0Conflict of interest: Motohiro Ebisawa and Sakura Sato have received speaker honoraria from Viatris. All other authors declare that they have no conflicts of interest.Financial support: This paper has not received any financial support.Keywords : low-dose oral food challenge, peanut, food allergy, low-dose-tolerant, tolerant, pediatric, anaphylaxisTo the Editor,Peanuts cause severe allergic reactions, and only 20% of peanut-allergic patients acquire tolerance.1 Peanut oral food challenge (OFC) has a high risk of severe symptoms such as anaphylaxis, and OFC is avoided in children with an immediate history, especially with a history of anaphylaxis.1Peanut-allergic patients and their guardians have a lower quality of life because of worry that anaphylaxis may occur at any time.2 Low-dose OFC may be useful to manage children with a history of anaphylaxis,3 but it has not been used to evaluate prognosis. This study investigated long-term prognosis after low-dose peanut OFC for patients with a history of immediate reactions, including anaphylaxis.We retrospectively analyzed participants with a history of immediate symptoms due to peanut ingestion, who received baseline low-dose OFC with 133 mg of peanut protein from August 2013–August 2017 at Sagamihara National Hospital (Figure 1), and evaluated two-year tolerance acquisition.We defined tolerance as passing an OFC with 795 mg protein (medium-dose OFC) and ingesting more than 795 mg protein without symptoms at home; consuming this dose enables cessation of strict avoidance in daily life. We defined baseline low-dose OFC negative patients as the low-dose-tolerant group and positive patients as the low-dose-reactive group. The low-dose-tolerant group was instructed to consume 133 mg at home twice a week. Then, based on guardians’ preference, patients received a medium-dose OFC every 6 months or gradually increased peanut ingestion to 795 mg at home under a physician’s direction. The low-dose-reactive group completely avoided peanuts and received low-dose OFC every 6 months. When the low-dose-reactive group passed low-dose OFC, they received medium-dose OFC (Supplementary Figure 1).Anaphylaxis was defined according to the World Allergy Organization Guidelines.4 OFC protocol is described in the supplementary information.5 The percentage of patients who acquired tolerance within two years was estimated using Kaplan-Meier curves. The co-factors for tolerance acquisition were analyzed using Cox regression analysis. Multivariate analysis was performed on the results of low-dose OFC, total IgE, peanut-specific IgE (Pn-sIgE), and history of peanut-related anaphylaxis. SPSS (version 27.0; SPSS Inc., Chicago, IL) was used for all analyses; p <0.05 was considered statistically significant. The Ethics Committee of The Sagamihara National Hospital (2016-015) approved the study according to the Helsinki Declaration. Written informed consent was obtained from all patients’ guardians.Fifty-three patients (median age, 7.1 years) were enrolled; 43% had a history of anaphylaxis. The median Pn-sIgE level was 20.7 (interquartile range 7.0–57.5) kUA/L. The median Ara h 2-specific IgE level was 10.4 (4.98–28.3) kUA/L. The median thresholds of past immediate symptoms were 26.6 mg (13.3–133) (Supplementary Table 1).Twenty-one patients (40%) passed the low-dose OFC and were defined as the low-dose-tolerant group, and 32 (60%) failed and were defined as the low-dose-reactive group (Supplementary Table 1); 35% of patients with a history of anaphylaxis passed the low-dose OFC. During low-dose OFC, oral mucosal symptoms were most common (72%), then gastrointestinal (63%) and respiratory symptoms (63%). Three patients required intramuscular adrenaline (Supplementary Table 2). When the low-dose-tolerant patients ingested low-dose peanuts at home, six (29%) had mild reactions like oral and throat discomfort; most reactions resolved naturally and did not require medical attention.In the low-dose-tolerant group, 13 patients (62%) acquired tolerance within 2 years, including five patients with a history of anaphylaxis, whereas in the low-dose-reactive group, one patient (3%), with no history of anaphylaxis, acquired tolerance (p <0.001) (Figure 2). In the low-dose-reactive group, 6% of patients passed low-dose OFC within two years.The predictive factors of failure to acquire tolerance have been positive reactions to low-dose OFC (crude hazard ratios of total IgE, Pn-sIgE: 0.37 [95% confidence interval 0.15–0.94, p =0.04), and log (Pn-sIgE) 2.23 [1.01–4.92], p =0.048) (Supplementary Table 3). In 23 patients with a history of anaphylaxis, five (22%) acquired tolerance. In 30 patients with no history of anaphylaxis, nine (30%) acquired tolerance. History of anaphylaxis did not significantly affect tolerance acquisition (Supplementary Figure 2).This is the first report showing that low-dose OFC can be undergone relatively safely with tolerance acquisition in some peanut-allergic patients, including patients with a history of anaphylaxis. Patients with a history of anaphylaxis have a lower quality of life because of worry that anaphylaxis may occur at any time.6 Therefore, these results are significant because if patients realize that low-dose peanuts can be ingested, complete avoidance becomes unnecessary, and tolerance acquisition could be assessed. The low-dose-reactive group was less likely to develop tolerance and required careful follow-up to prevent accidental ingestion.Previous studies of long-term prognosis after peanut OFC excluded patients with a history of anaphylaxis,1 therefore, their tolerance acquisition based on the results of OFC was unknown. In our current study, more than half of patients in low-dose-tolerant groups acquired tolerance within two years, even those with a history of anaphylaxis. Furthermore, one-fifth of patients with a history of anaphylaxis tolerated peanuts, and there was no significant difference between patients with and without a history of anaphylaxis in acquiring tolerance. Therefore, passing low-dose OFC could be considered to assess tolerance acquisition, regardless of the history of anaphylaxis.It has been reported that peanut OFC is high risk because it often causes anaphylaxis and other serious symptoms.1 In the previous studies of peanut OFC, subjects have no history of anaphylaxis or as few as 10%, while this study had 40%, but the occurrence of anaphylaxis in OFC was comparable.1,7 Furthermore, there is a report of a group of subjects, 83% of whom had a history of anaphylaxis, and all patients reacted with anaphylaxis in OFC.8 It has been reported that the incidence of anaphylaxis with OFC was higher with progression up to the total OFC ingested.7 Therefore this study suggests that low-dose OFC is relatively safe in patients with a history of anaphylaxis.Recently, some trials of low-dose oral immunotherapy showed that ingesting low-dose peanuts (133-300 mg) could induce immunological changes and allow the intake of larger amounts.9Similarly, daily ingestion of low-dose wheat is effective in increasing consumption dose and preventing accidental symptoms, even in patients with a history of anaphylaxis.10 Therefore, twice weekly ingestion of 133 mg in the low-dose-tolerant group may yield oral tolerance. In addition, few serious reactions were observed in the low-dose-tolerant group during the subsequent at-home dose escalation in this study.This study has several limitations. First, 33 subjects were excluded because their two-year course could not be tracked. Although the excluded and included patients’ backgrounds were similar (Supplementary Table 4), predictors of tolerance acquisition, such as anaphylaxis may be different with more subjects. Second, there was a lack of information on several points. Although at-home intake methods were unified, the frequency of home peanut intake and adherence was unknown. Additionally, we couldn’t confirm thresholds of past immediate symptoms in 25% of subjects. However, the median thresholds were 26.6 mg in 75% of subjects who were able to assess the threshold. Therefore, we assume that thresholds in the remaining children were similar.For peanut-allergic patients with a history of anaphylaxis, low-dose OFC is relatively safe and effective in the assessment of tolerance acquisition. Low-dose OFC results may effectively stratify peanut-allergic patients with anaphylaxis history with good and poor tolerance acquisition to select optimal management plans.Nobuko Akamatsu, MD, PhD1,2, Ken-ichi Nagakura, MD, PhD1, Sakura Sato, MD3, Noriyuki Yanagida, MD, PhD1,3, Motohiro Ebisawa, MD, PhD3,1Department of Pediatrics, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan2Department of Pediatrics and Adolescent Medicine, Tokyo Medical University Hospital, Tokyo, Japan3Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Kanagawa, Japan

The continuous exploitation of groundwater has made wetland degradation an ecological and geological environmental problem that cannot be ignored and which has had impacts on the ecological environment and human production and life. In this study, with the help of Visual MODFLOW software, we used numerical simulation technology to simulate the wetland–aquifer interaction during the multiyear pumping process, establish a quasi-ideal model of wetlands based on the actual area of the Baiyangdian Basin, simulate the relationship of water quantity change between wetlands and piedmont plain aquifers during groundwater exploitation and its natural recovery process, and quantify the attenuation of the contribution of groundwater to wetlands caused by groundwater overexploitation. The results show that the impact of groundwater overexploitation on wetland degradation is mainly divided into two parts: one is the reduced base flow from the piedmont plain to the wetland, and the other is the induced infiltration caused by the reverse recharge of groundwater from the wetland due to the pumping effect. At the beginning of pumping, the effect of reduced base flow on wetland degradation is dominant, but with a longer pumping time, the effect of induced infiltration on wetland degradation exceeds the effect of reduced base flow. After stopping pumping, the effect of induced infiltration on wetland degradation responds instantly and decreases rapidly, while the effect of reduced base flow on wetland degradation continues for a long time. The total water reduction of wetlands increases with increasing hydraulic conductivity, and in actual wetland areas, if groundwater overexploitation is not restricted or artificial supply measures are not taken, the amount of wetland water will gradually decrease until it is exhausted.

Tetraodontiformes is a special group of higher teleosts, with a long and problematic taxonomic history due to their wide distribution and species diversity. It is a difficult task for both professionals and nonprofessionals to accurately identify all species only according to morphological characteristics. DNA barcoding can identify species at the molecular level. In this study, we collected 616 specimens of Tetraodontiformes and their DNA barcodes from the coastal waters of China. According to the morphological characteristics, 50 species were preliminarily identified, belonging to 23 genera, 6. Among them, DNA barcoding analysis showed that Takifugu pseudommus and Takifugu chinensis are the synonyms of Takifugu rubripes. And Lagocephalus wheeleri is the synonym of Lagocephalus Spadiceus. The third important finding is that the species of Takifugu have close genetic relationship. If T. rubripes, T. pseudommus and T. chinensis are taken as one species, the average interspecific genetic distance of Takifugu is 6.21 times of the average intraspecific genetic distance, which does not reach the DNA barcode threshold of more than 10 times proposed by Hebert. Among them, the genetic distance between T. oblongus and T. stictonotus is the largest, 0.045; And between T. bimaculatus and T. flavidus is the smallest, only 0.013. However, species can be clustered into separate clades in the NJ tree. In conclusion, this study provided molecular basis for solving the problem of confusion in the classification of Tetraodontiformes, it found that there are synonym phenomena in the order, and provided molecular evidence for clarifying the valid species names of Lagocephalus Spadiceus and Takifugu rubripes. The results can provide reliable DNA barcoding information for the identification and classification of Tetraodontiformes, and also provide technical support for the development and utilization of puffer fish resources and the identification of the original components of related commodities on the aquatic product market.

Lactate dehydrogenase reflects the status of ultra-high-risk neuroblastoma in a child under treatmentAkinori Yaguchi, Junya Fujimura, Ayane Yakabe, Megumi Fujiwara, Takeshi Ishibashi, Osamu Tomita, Toshiaki ShimizuDepartment of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

CF is considered a rare disease among the non-Caucasian population. The clinical phenotypes and genotypic spectrum of Chinese CF patients are reported to be different from that observed in Caucasians[(1)](#ref-0001). Our patient carried compound heterozygous mutations which are not included in the Caucasian CFTR common mutation-screening panel and have not been reported yet. CFTR dysfunction causes a spectrum of diseases, with a range in the number of organs involved and varying disease severity. Typical phenotypic features of CF include respiratory diseases (bronchiectasis with persistent airway-based infection and inflammation), gastrointestinal diseases (meconium ileus (MI)), hepatobiliary manifestations (pancreatic insufficiency), and male infertility[(2)](#ref-0002). Our patient presented severe manifestations, namely colonic perforation, meconium thorax, severe pneumonia, diaphragmatic defects-caused marked diaphragm elevation and respiratory failure. It’s difficult to ascertain whether the diaphragmatic defects in our patient is related to CF. MI is often the first manifestation of CF and occurs in approximately 20% of CF patients. CF should therefore be high in the differential diagnosis of any infant presenting with MI[(3)](#ref-0003).

Title: Reply to Migration is not the perfect answer: Optimised methodology to assess LCI agreement between corrected legacy multiple breath nitrogen washout data and that directly collected on updated software.

VACTERL association is linked to multiple congenital anomalies including tracheoesophageal fistula. In rare cases, VACTERL has been complicated by other airway malformations including severe bronchial stenosis or unilateral pulmonary agenesis. We report a child who developed episodes of oxygen desaturation during sleep associated with high pressure support requirements to maintain ventilation. He was known to have VACTERL association as well as spinal muscular atrophy (SMA) type II, a genetic neuromuscular disorder. Children with SMA can show progressive respiratory symptoms, including intercostal muscle weakness and accompanying paradoxical abdominal breathing with sparing of diaphragm function. Our patient was very difficult to ventilate non-invasively despite high pressures. CT chest with dynamic airway evaluation showed bilateral bronchial stenosis. High inspiratory pressures with non-invasive ventilation as seen in our case are required to overcome stenotic airways but are not expected in neuromuscular respiratory failure.

The irregular pulse notification (IPN) algorithm on the Apple Watch (Apple Inc., Cupertino, CA) was not designed for use by atrial fibrillation (AF) patients. It is not FDA cleared for use in AF patients. Before this study by Dr. Wasserlauf and colleagues, there were no studies of its accuracy in AF patients. Yet, many AF patients could not resist the temptation to use the feature. In the Apple Heart Study1, even after making it clear that patients with AF were not eligible for the study, 174 (18%) of the participants who received an irregular pulse notification and connected with a study visit doctor confessed that they knew they already had AF and were excluded from the study. These participants were just too curious to pass up the opportunity to see what the new technology was all about.

Climate change is increasing the weather persistence in the mid-latitudes, prolonging both dry and wet spells compared to historic averages. These newly emerging environmental conditions destabilize plant communities, but the role of species interactions in this process is unknown. Here, we tested how direct and higher-order interactions (HOIs) between species may change in synthesized grassland communities along an experimental gradient of increasing persistence in precipitation regimes. Our results indicate that species interactions (including HOIs) are an important determinant of plant performance under increasing weather persistence. Out of the 12 most parsimonious models predicting species productivity, 75 % contained significant direct interactions and 92 % significant HOIs. Inclusion of direct interactions or HOIs respectively tripled or quadrupled the explained variance of target species biomass compared to null models only including the precipitation treatment. Drought dominated the plant responses, with longer droughts increasing direct competition but also HOI-driven facilitation. Despite these counteracting changes, drought intensified net competition. Grasses were generally more involved in competitive interactions whereas legumes had a stronger affinity for facilitative interactions. Under longer drought, species affinity for nutrient rich or wet environments resulted in more negative direct interactions or HOIs, respectively. We conclude that higher-order interactions, crucially depending on species identity, only partially stabilize community dynamics under increasing weather persistence.

A Case of Close Lip Schizencephaly with absent septum pellucidum in adult presenting with seizure disorderChhabi Khadka1, Umang Gupta2, Prakriti Bhandari3, Prabin Pandey1, Shailes Paudel3National Academy of Medical Sciences, NepalMaharajgunj Medical Campus, NepalPatan Academy of Health Sciences, Nepal Correspondence: Shailes Paudel, Patan Academy of Health Sciences, Lalitpur, Nepal Email: [email protected]

An Unusual Cause of Chronic Diarrhea in a Young Patient – Diagnostic Challenge

A document by Jiangbo Cui. Click on the document to view its contents.

Maternal lineages of mitochondrial DNA (mtDNA) are recognized as important components of intra- and inter-specific biodiversity and help us to disclose the phylogeny and divergence times of many taxa. Species of the genus Capra are canonical mountain dwellers. Among these is the Siberian ibex (Capra sibirica), which is regarded as a relic species whose intra-specific classification has been controversial so far. We collected 54 samples in Xinjiang, China, and analyzed the mtDNA genes to shed light on the intra-specific relationships of the C. sibirica populations and estimate the divergence time. Intriguingly, we found that the mtDNA sequences of C. sibirica split into two main lineages in both phylogenetic and network analyses: the southern lineage, sister to C. falconeri, consisting of samples from India, Ulugqat, and Kagilik in Xinjiang; and the northern lineage further divided into four monophyletic clades A–D corresponding to their geographic origins. Samples from Urumqi, Sawan, and Arturk formed a distinct monophyletic clade C within the northern lineage. The genetic distance between the C. sibirica clades ranges from 3 to 8.6 percent, with values of FST between 0.72 and 0.95, indicating notable genetic differentiation. The split of the genus Capra occurred approximately 6.75 Mya during the late Miocene. The northern lineage diverged around 5.88 Mya, following the divergence of Clades A–D from 3.3 Mya to 1.9 Mya during the late Pliocene and early Pleistocene. The radiation between the southern lineage and C. falconeri occurred at 2.29 Mya during the early Pleistocene. Our results highlight the importance of extensive sampling when relating to genetic studies of alpine mammals and call for further genomic studies to draw definitive conclusions.

Introduction: Obesity is a major risk factor in the development of endometrial cancer (EC) in young patients of reproductive age. Fertility sparing treatment is a viable option for a select group of patients with early EC, and involves systemic and intra-uterine hormonal therapy. Weight loss has been associated with improved outcomes in this group. Bariatric surgery (BS) has been shown to be the most efficient and durable method of weight loss in obese patients. However, there is a paucity of data studying the benefit of BS as part of fertility sparing treatment. Methods: We present a retrospective case series of five patients who are undergoing fertility sparing treatment for early EC, who also underwent BS for treatment of obesity and related comorbidities. We aim to show early regression of EC for all the patients and also report on the other health benefits of BS. Results: All five patients in the series achieved regression of EC within six months of undergoing BS. They also achieved significant weight loss consistent with previous studies, and three patients who had comorbidities related to obesity had remission of these conditions. One of the patients with EC regression also managed to conceive with IVF. Conclusion: Patients on fertility sparing treatment for early EC who underwent BS was associated with early regression within 6 months, significant weight loss and resolution of comorbidities. BS could be a promising component of fertility sparing treatment. Long term, prospective studies are required to confirm the benefits reported in this case series.

Background: As the ongoing public health crisis from Coronavirus Disease 2019 (COVID-19) pandemic puts strains on current models of cancer care, many health care centers had to adapt to minimize the risk of exposure and infection. The effects of the COVID-19 pandemic in a comprehensive cancer center were determined. Purpose: To measure the impact of the COVID-19 pandemic on care delivery at a comprehensive cancer center. Methods: The number of on-site and telehealth visits (TH) were obtained from scheduling software. Multiple factors including total visits, telehealth visits, screenings for cancer diagnosis, and cancer treatments were tracked from two years before the pandemic onset through 2022. The length of stay (LOS) and Case Mix Index (CMI) were calculated using hospital database. Results: In the third quarter of FY 2020, telehealth visits (TH) represented a fifth of total patient encounters. Cancer treatments, such as chemotherapy, radiation therapy, and surgery, decreased during the pandemic with number of surgeries being most affected (23% decrease in 2020 compared to the previous fiscal year). The average length of stay (LOS) was also longer with less discharges per given time during the pandemic. The increased LOS was related to increased severity of patient illnesses since CMI was higher. Screening mammograms decreased to a nadir of 58% in 2021 as compared to those screened in pre-pandemic fiscal years. Conclusions : The COVID-19 pandemic impacted many aspects of care, such as treatment and screenings. Many of these factors had to be postponed due to the fear of acquiring COVID-19 and access to care. The findings presented implicate that the delays and changes in cancer care during the pandemic resulted in less screening and treatment of more advanced disease.