Background. Allergic bronchopulmonary aspergillosis (ABPA) is an underestimated allergic disease due to Aspergillus fumigatus (AF). The main diagnostic criteria for ABPA rely on the evaluation of immunoglobulin (Ig) E and IgG responses to AF extracts, although these cannot discriminate AF-sensitization from ABPA. Objectives. To evaluate the performance of cellular functional assays with extract and molecular AF allergens in ABPA. Methods. A prospective cohort of 67 patients (6 ABPA) was investigated with basophil activation test (BAT) and lymphocyte stimulation test (LST) with AF extract. Nine patients were further investigated for BAT responses to molecular AF components: Asp f 1, Asp f 2, Asp f 3, Asp f 4 and Asp f 6. BAT supernatant was assessed for cytokine production. Results. BAT with AF extract with an optimized cutoff displayed 100% sensitivity and 77.6 % specificity for ABPA diagnosis. Among patients with positive BAT to AF, BAT with Asp f 4 was significantly higher in ABPA patients at 10 ng/mL (mean basophil stimulation index 10.56 in ABPA vs 1.24 in non-ABPA patients, p = 0.0002). High LST with AF extract was associated with ABPA occurrence three months after the test. No significant ex vivo cytokine release was observed in BAT supernatants. Conclusion. BAT with AF is a promising diagnostic biomarker in the context of suspected ABPA, which can be further improved with AF molecular allergens, especially Asp f 4. LST with detection of AF-induced activation of peripheral T cells suggests an underlying pathophysiological process and may predict ABPA occurrence.

ABSTRACT Objective: Female stress urinary incontinence is one of the common diseases in menopausal women, which brings great inconvenience to life. We conducted a meta-analysis to evaluate the efficacy of magnetic stimulation (MS) in treating female stress urinary incontinence (SUI). Methods: The electronic databases (E-DB) MEDLINE, EMBASE and Cochrane Controlled Trial Registry system was used to retrieve the randomized controlled trials (RCTs) which recorded MS as a remedy to female SUI. Reference lists of related papers were carefully studied. Results: Six RCTs exploring the effect of MS in the treatment of female SUI were studied. We found that the MS group enjoyed a higher quality of life (QoL) (MD of 0.59, 95% CI of 0.23 to 0.95, P=0.001) and lower International Consultation on Incontinence Questionnaire (ICIQ) scores (MD of -3.93, 95% CI of -5.86 to -2.01, P<0.0001) and provided a higher objective cure rate (odds ratio [OR] of 8.49, 95% CI of 3.08 to 23.37) compared with the placebo group. Apart from this, MS treatment reduced the number of episodes of urinary incontinence (MD of -1.42, 95% CI of −2.24 to −0.59, P=0.0007) and urine loss on pad test (MD of −4.67 and 95% CI of −8.05 to −1.28, P=0.007). No significant treatment-related adverse reactions were reported. Conclusion: MS treatment showed a positive effect in the treatment of SUI and further trials are required to specify the best protocol to optimize the effect.

Background：Menopause-related symptoms are now a major public health concern and depression is one of the most common and specific symptoms of post-menopause. Objectives: The purpose of this study was to assess the effectiveness of different kinds of phytoestrogens in the remission of depression for postmenopausal women. Methods: A comprehensive search for relevant studies published between January 1, 1951 and June 30, 2020 was conducted in PubMed, the Cochrane Library, Chinese Biomedical Literature Database, Web of Science and EMBASE. Endnote X9 was used for screening articles, the Stata12.0 and Review Manager 5.3 for analyzing data. Results: Phytoestrogens had a have a significant positive effect on depressive symptoms for climacteric women compared to the placebo (SMD=-0.51; 95% [CI]=-0.74 to -0.29; I2=72.4%; P<0.05). The effectiveness in isoflavones (SMD=-0.64; 95% [CI]=-0.97 to -0.32; I2=56.2%, P>0.05) is slightly better than non-isoflavones (SMD=-0.5; 95%[CI]=-93 to -0.07; I2=72.8%, P<0.05). The total intake of phytoestrogens in the high dose group was the most effective in alleviating the symptoms of postmenopausal depression (SMD=-0.69; 95%CI=-1.09 to -0.35, P<0.05). Postmenopausal women in Europe had the best improvement in efficacy after taking phytoestrogens (SMD=-0.72, 95% CI=-1.09 to -0.35, I2=65.5%, P<0.05). Conclusions: Our study demonstrated that phytoestrogen significantly reduce depression among postmenopausal women, with more effect for larger dosages. Phytoestrogen should be considered as a safe and effective complementary medicine for postmenopausal symptoms in place of estrogens.

Aim: Non-alcoholic fatty liver disease (NAFLD) is one of the metabolic disorders related with inflammation. Nigella sativa (NS) has various chemical compounds includes thymoquinone (TQ), unsaturated fatty acids and flavonoids. NS is used as anti-inflammatory and anti-oxidant in medical science. The aim of this study was to investigate the effect of NS oil supplementation on levels of adiponectin, leptin and blood pressure in patients with non-alcoholic fatty liver. Methods: This randomized, double-blind, placebo-controlled clinical trial was performed among 44 patients diagnosed with NAFLD. Subjects were randomly assigned to placebo group (n=22) and/or intervention group (n=22), supplemented with 1g/day of NS oil. The duration of the intervention was 8 weeks. Blood samples were collected at baseline and at the end of the intervention and serum levels of adiponectin, leptin and systolic and diastolic blood pressure were measured. Results: NS oil supplementation did not have a significant effect on serum levels of adiponectin and leptin. Also, no significant effects were seen with this supplementation on systolic and diastolic blood pressure among patients with NAFLD. Conclusions: In the current trial, 8 weeks of nigella sativa oil supplementation demonstrated did no significant effects on serum levels of adiponectin, leptin and blood pressure in people with NAFLD.

Aim: To investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of the highly selective oral p38α/β MAP-kinase inhibitor Org 48775-0, a first-in-human study was conducted. Methods: In the SAD study part, an oral dose of Org 48775-0 ranging from 0.3 mg to 600 mg was evaluated in healthy males. In the MAD study part, dose levels of 30, 70 and 150 mg were evaluated with dosing for six consecutive days, twice daily. Both studies were performed in a double-blind, randomized, placebo-controlled, cross-over fashion and evaluated pharmacokinetics (PK), pharmacodynamics (PD; inhibition of LPS-induced TNFα release) and routine clinical and laboratory data. Moreover, the effect of a standardized fat meal on PK and PD parameters of Org 48775-0 was evaluated, and PK and PD parameters of Org 48775-0 were compared between healthy males and postmenopausal females. Results: All adverse events observed in the SAD and MAD cohorts were mild, transient and completely reversible without medical intervention. Pharmacokinetics were linear up to single dose s of 400 mg. Org 48775-0 doses equal to and greater than 30 mg significantly inhibited LPS-induced TNFα release (42.3% increase in inhibition, 95% CI=-65.2; -4.3) compared to placebo. In the MAD study, Org 48775-0 treatment inhibited the LPS-induced TNFα release during the entire steady state period. Levels of inhibition amounted 30-75% for 30 mg, 53-80% for 70 mg, and 77-92% for 150 mg Org 48775-0. Conclusion: This study demonstrates that Org 48775-0 has the capacity to significantly inhibit MAP-kinase activity in humans, without raising safety concerns.

Objective: Atrial fibrillation (AF) is a common and clinically relevant supra-ventricular arrhythmia which represents an independent risk factor for development of heart failure as well as for ischemic stroke. Clinical management of this pathology can be still challenging in many patients, in particular the older ones and/or those which present comorbidity. The interest in biomarkers for diagnosis and management of the AF becomes more evident in recent years. We studied the possible role of the soluble sST2 and the GDF15 as biomarkers to stratify the risk of patients with persistent or permanent AF. Method: The serum concentrations of these biomarkers have been measured in a group of 58 patients (mean age 83.6  6.0 years) and in a control set of 40 individuals. Results: The mean serum concentration of sST2 is 22.6 (18.85-25.35) ng/mL in the AF group, while in the control is 17.25 (15.7-18.9) ng/mL (p<0.05). The corresponding data for the GDF15 are 1579 (975-3213) pg/mL and 850 (438-1234) pg/mL, respectively. Remarkable differences have been obtained for the two subsets of patients with persistent and permanent AF (sST2: (23 (21.2-24) ng/mL vs 30 (28.6-32) ng/mL, GDF15: 1347 (837-3320) vs 1931 (1238-3178)). The analysis has been completed with a trans thoracic echocardiographic exam to evaluate the left atrium size and the left ventricular ejection fraction. The results have been discussed to enhance the correlation between the instrumental and laboratory results. Conclusions:The present study suggests a possible clinical valuable role of the two biomarkers considered to refine the stratification risk in patients as the cohort here studied. A comparison between the two biomarkers is presented and discussed. The main pathological conditions that could increase the biomarkers are evaluated.

Background This study was undertaken to evaluate the clinical characteristics and perinatal outcomes of pregnant women with COVID-19 in different trimesters and to determine the possibility of vertical transmission of the disease. Methods Medical records of 25 consecutive pregnant women with laboratory-confirmed COVID-19 who were admitted to Renmin Hospital of Wuhan University, Wuhan, China, from Feb 1 to Mar 20, 2020 were reviewed. Results Eleven cases were in early and middle pregnancy, and 14 cases were in late pregnancy. Seven of 25 women (28.0%) had mild disease, 15 (60.0%) had moderate disease, and 3 (12.0%) had severe disease. The most common symptoms of patients were fever (48.0%) and cough (48.0%), though 7 (28.0%) of them were asymptomatic at admission. Fever was more prevalent in early and middle pregnancy than in late pregnancy (72.7% vs. 28.6%, P=0.028). Among patients in early and middle pregnancy, there were 1 spontaneous abortion and 3 induced abortions, but no intrauterine growth restriction was observed among ongoing pregnancies. All 14 patients in late pregnancy underwent a cesarean section, with 4 premature deliveries (28.6%). No neonatal asphyxia or death was recorded. Nasopharyngeal swab samples from 6 neonates were tested for SARZ-CoV-2, and all were negative. In one neonate, the anal swab was positive for SARS-CoV-2, and IgG and IgM were increased. Conclusions The clinical characteristics of COVID-19 in early and middle pregnant women were similar to those in late pregnancy. There is a potential risk of vertical transmission in SARS-CoV-2.

The Contribution of Neurocognitive Situation, Physical Capacity and Daily Life Activities to Quality of Life after Childhood Acute Lymphoblastic Leukemia Elif Keles1, Yağmur Çam2, Bülent Elbasan2, Şebnem Soysal Acar1, Zühre Kaya3, İdil Yenicesu3, Ülker Koçak3

The coagulopathy of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is well documented in adults, with increases in D-dimer and prothrombin time strong predictors of mortality and anticoagulation shown to decrease this mortality. Viscoelastic parameters such as elevations in maximum clot firmness (MCF) on rotational thromboelastometry (ROTEM) have correlated with a hypercoagulable state in adults with SARS-CoV-2. We report our experience in children infected with SARS-CoV-2, with noted elevations in D-dimer and MCF on ROTEM (indicating hypercoagulability). Exploration of viscoelastic testing to provide additional laboratory-based evidence for pediatric-specific risk-assessment for thromboprophylaxis in SARS-CoV-2 is warranted.

LPS produced by Gram-negative bacteria effectively stimulates the maturation of BMDCs. Previous studies have shown that DClps might induce tolerance in autoimmune diseases and cancer in vivo, whereas it remains unclear whether DClps can modulate the immune microenvironment in allergic asthma. We sought to elucidate the potential effects of DClps on OVA-sensitized/challenged airway inflammation in a mouse model of asthma, which may help facilitate the application of specific tolDCs in allergic asthma patients in the future. We generated and obtained DClps from wild-type mice to evaluate their functional characteristics by ELISA and FACS. We also induced OVA-sensitized/challenged asthmatic mice and intraperitoneally treated these mice with DClps to assess the effects of these injected cells by histopathologic analysis and performing inflammatory cell counts in BALF. Changes in memory CD4+ T cells, Tregs and phosphorylated protein in lung digests were analyzed. DClps exhibited lower levels of CD80 and MHCII and increased levels of anti-inflammatory cytokines such as IL-10 and TGF-β than DCia. Additionally, DClps treatment dramatically ameliorated airway inflammation and diminished the infiltration of pulmonary inflammatory cells. In addition, we prolonged the modeling time of asthmatic mice and demonstrated that DClps treatment decreased the proliferation activity of pulmonary memory CD4+ T cells, which further rendered the downregulation of Th2 cytokines. However, the number of pulmonary Tregs did not discernibly change. DClps treatment also markedly reduced the phosphorylation level of STAT6 protein.

As we celebrate 2020 as the Year of the Nurse and the Midwife and recognize the Global Initiative for Childhood Cancer, members of the International Society of Pediatric Oncology (SIOP) Baseline Nursing Standards Taskforce would like to highlight advocacy efforts promoting the baseline nursing standards.1, 2 Your published article, An ethical imperative: safety and specialization as nursing priorities of WHO Global Initiative for Childhood Cancer(Pergert and colleagues) reveals the importance of ongoing efforts to support implementation of the Baseline Nursing Standards.3 Given that the majority of hospitals are not meeting the standards in low- and middle-income countries (LMIC), as well as some high-income countries (HIC),4, 5 advocacy initiatives are required to raise awareness of the need to meet these standards. During the COVID-19 pandemic, health facilities face new challenges in meeting the standards. To achieve the WHO global initiative’s goal to save one million children’s lives by 2030, it is important to continue efforts to address baseline nursing standards.Pediatric oncology as a subspecialty requires a nursing workforce with specialized education and clinical skills to achieve optimal patient outcomes. Knowledge itself is not enough if nurses lack the resources and support to practice or implement appropriate nursing care in their work settings. The six Baseline Nursing Standards focus on key elements essential to delivering quality and safe care (Table 1). Collectively, they serve as a framework and foundation for positive pediatric oncology nursing practice environments internationally.Advocacy efforts to disseminate the baseline standards are well established. To date, fourteen organizations have endorsed the Standards. Members of the SIOP PODC Nursing Working Group hosted a “Leadership and Advocacy Workshop: Disseminating the Baseline Nursing Standards” prior to the SIOP Conference in October 2017. Twenty-two pediatric hematology/oncology nurse leaders and four stakeholder-group representatives (parent, physicians, advocates) from 14 countries met and established goals and strategic priorities for advocacy of the standards. As a result, the Baseline Nursing Standards Advocacy Toolkit was developed and can be found on the SIOP Nursing Website https://siop-online.org/baseline-nursing-standards-advocacy-toolkit. The toolkit contains practical advocacy resources, including a PowerPoint presentation, an endorsement letter template, publications, podcasts, a social media campaign and examples of elevator speeches for each standard. Furthermore, the Standards have been featured in international presentations, such as a keynote presentation (S. Day) in SIOP Lyon, an award session and nursing abstract presentations at SIOP congresses and continental meetings.To reach the WHO target of doubling the global childhood cancer survival rate to 60%, achievement of baseline nursing standards for pediatric oncology must be prioritized and appropriately resourced by hospital administrators, governments and other stakeholders. Amid a global pandemic where nursing resources are stretched, creative ways to support and advocate for implementation of the standards is needed. In recognition of the recent publication by the Nurse Specialists of the Global Initiative for Childhood Cancer noting the baseline standards, now is the time to act and improve childhood and adolescent cancer outcomes through raising the standard of pediatric oncology nursing practice around the world.Linda Abramovitz, Rehana Punjwani, Glenn M. Afungchwi and Courtney Sullivan and the SIOP PODC Baseline Standards Nursing Task Force.A special thank you to Rachel Hollis for her commitment and ongoing advocacy efforts focused on the baseline nursing standards.ReferencesDay S, Hollis R, Challinor J, Bevilacqua G, Bosomprah E, SIOP PODC Nursing Working Group. Baseline standards for paediatric oncology nursing care in low to middle income countries: position statement of the SIOP PODC Nursing Working Group. Lancet Oncol. 2014; 15(7):681-682 PMID: 24872097.Day S, Challinor J, Hollis R, Abramovitz L, Hanaratri Y, Punjwani R. Paediatric Oncology nursing care in low-and middle-income countries: a need for baseline standards. Cancer Control. 2015;2015:111-116Pergert P, Sullivan CE, Adde M, et al. An ethical imperative: Safety and specialization as nursing priorities of WHO Global Initiative for Childhood Cancer. Pediatr Blood Cancer. 2019;e28143. https://doi.org/ 10.1002/pbc.28143Morrissey L, Lurvey M, Sullivan C, et al. Disparities in the delivery of pediatric oncology nursing care by country income classification: international survey results. Pediatr Blood Cancer. 2019;66(6):e27663.Sullivan CE, Morrissey L, Day SW, Chen Y, Shirey M, Landier W. Predictors of Hospitals’ Nonachievement of Baseline Nursing Standards for Pediatric Oncology. Cancer Nurs. 2019 Mar 29;

Developing host-directed therapies against resistant tuberculosis requires a better understanding of the changes in the innate immune response of the peripheral blood monocytes. Here, we investigated the phagocytic capacity of blood phagocytes, the changing of the mammalian target of rapamycin (mTOR) pathway and autophagy process of circulating monocytes in untreated tuberculosis patients. Phagocytic capacity of blood phagocytes and the expression of key regulators of the mTOR pathway were analysed using flow cytometry. We detected the mRNA and protein expression of autophagy proteins using RT-PCR and capillary western blotting. Compared with healthy controls, the increase of monocytes phagocytizing E.coli was lower in tuberculosis patients after 37°C activation (15.46% vs. 23.31%); The percentages of Rheb+ and mTOR+ Raptor+ circulating monocytes were higher, while that of AMPK+ monocytes were lower. Although ATG5 and ATG12 mRNA expression increased, the protein complex expression was decreased in the monocytes of tuberculosis patients. Beclin-1 and ULK1 Ser 757 levels were increased at both transcriptional and protein levels; LC3 II protein level also was higher. Our current study suggests a decrease in the phagocytic capacity of circulating monocytes, accompanied by autophagy activation in active tuberculosis patients.

Background: The majority of patients with high-risk neuroblastoma (HR-NB) in low- and middle-income countries (LMIC) do not have access to autologous stem cell transplant (ASCT) and dinutuximab. Consolidation with non-myeloablative chemotherapy is not well-defined, and the outcomes are variable. We report a single-center outcome of patients with HR-NB, treated with non-myeloablative consolidation. A tabulated compilation of similar reports is included. Procedure: A retrospective chart review of patients with HR-NB was performed from January 2009 till June 2016. Patients were treated on the backbone of HR-NBL1/SIOPEN protocol. Treatment included induction with rapid-COJEC, surgery, consolidation, radiotherapy to the primary tumor, and differentiation therapy with isotretinoin. Consolidation included 4 cycles of topotecan, vincristine, and doxorubicin (TVD) instead of ASCT. Infusion of vincristine and doxorubicin were modified for ease and to enable administration in daycare. Results: Over 7-½ years, 28 patients with HR-NB were treated. Two (7%) patients had therapy-related mortality. A relapse or disease progression occurred in 11 (39%) patients at a median duration of 17 months (IQR: 5, 18). Treatment abandonment was observed in 4 (14%) patients. The 4-year event-free survival was 29.3%. The median follow up of disease-free patients is 49 months (IQR: 45, 79). Patients with relapse were not treated further. Conclusions: A 4-year EFS of 29.3% was observed when 4-cycles of TVD were administered instead of ASCT in patients with HR-NB. The study and the review will aid stakeholders in LMIC for decision-making while considering the options of treatment for HR-NB if access to ACST and dinutuximab is lacking.

Background: Most of the pregnant women with 2019 novel coronavirus pneumonia are terminated by cesarean section because the risk of mother-to-child transmission is not yet clear. The aim of this study was to evaluate maternal and perinatal outcomes of vaginal delivery of pregnant women with COVID-19 infection. Design: 8 pregnant women who were suspected or confirmed with COVID-19 infection between 31 January and 20 April,2020, gave birth vaginally in Wuhan Union hospital were included. Clinical manifestations, laboratory test results, chest CT scans and maternal and perinatal outcomes were recorded. Evidence of perinatal infection of virus was assessed by using SARS-COV-2 associated coronavirus reverse-transcriptase polymerase chain reaction in neonatal throat and anal swab samples. Results: None of the 8 pregnant women experienced dystocia and severe postpartum complications, 8 livebirths were recorded, no fetal distress or asphyxia was observed. No newborn infant had clinical COVID-19 and all investigations were negative for SARS-COV-2. Conclusions: Our study showed that vaginal delivery does not increase the probability of mother-to-child transmission of SARS-COV-2，maternal and neonatal outcomes were not affected. We suggest that pregnant women with COVID-19 pneumonia without severe systemic complications and respiratory failure can be considered for vaginal delivery.

Objective: Current tests available to diagnose fetal hypoxia in-utero lack sensitivity thus un-diagnosing many fetuses at risk. microRNAs derived from the placenta circulate in the maternal blood during pregnancy and may be used as biomarkers for pregnancy complications. To identify putative markers of fetal growth restriction (FGR) and new therapeutic druggable targets, we examined, in maternal blood samples, the expression of a cluster of microRNAs, known to be regulated by hypoxia. Population: Pregnant Caucasian women between 18 and 46 years old hospitalized. Design and Setting: To discriminate between early- and late-onset FGR, the study population was divided into two subgroups according to the gestational age at delivery, group (1) : <32th weeks of gestation; and group (2) from 32th to 37th weeks of gestation. Methods: Ultrasound biometry, Doppler velocimetry, RT-PC-R, Software miRNA-targets predictors Results: Among the microRNA cluster examined, three microRNAs: miR-16-5p, miR-103-3p, and miR-27b-3p were upregulated in FGR blood samples before the 32th week of gestation. Notably, the expression of all miRNAs was increased through gestation in healthy control group, whereas, in the FGR groups, where there was a progressive reduction in the expression of miR-103-3p and miR-107-3p and a slight reduction for miR-16-5p. Main Outcome Measures: miRNA expression Conclusions: Our results showed that measurement of miRNAs in maternal blood may form the basis for a future diagnostic test to determine the degree of fetal hypoxia in FGR, thus allowing the start of appropriate therapeutic.

The Langerhans Cell Histiocytosis (LCH) is a disease characterized by the clonal proliferation of Langerhans cells. Patients with this diagnosis can present several manifestations in the oral cavity frequently found are bone lesions and periodontitis. The diagnosis is made with histological and immunohistochemical tests and the main form of treatment is chemotherapy. OBJECTIVE: To evaluate the presence of pathogenic bacteria, bone, dental conditions and manifestations in the oral cavity. METHODS: For this, a study was carried out with patients with LCH, they were submitted to oral swab, simplified periodontal examination (PSR), and panoramic radiography. RESULT: It was found that 36.8% of patients had pathogenic bacteria such as Staphylococcus aureus (10.5%). The PSR showed that 73.6% of the patients had a probing depth of the gingival sulcus of 3 mm or more in the maxilla region and 63.1% in the mandible (moderate periodontitis). The patients presented varied manifestations on the radiograph, such as veiling of the maxillary sinuses (33.3%). CONCLUSION: As it is a disease that affects the oral cavity, it is important that the dentist knows its manifestations and can be diagnosed and treated early in order to reduce mortality, morbidity and promote quality of life for patients.

Microsatellites are a set of repeating base sequences of one to several bases in a chromosome. In general, mismatch repair (MMR) proteins correct the base mismatches that occur during DNA replication. However, tumor cells with deficient MMR function accumulate genetic mutations and cause changes in the repeat counts in microsatellite sites, and such a status is referred to as microsatellite instability (MSI)-high status. According to recent research, MSI-high status is associated with responsiveness to therapies with immune checkpoint inhibitors [1].MSI status has been well described in various adult solid tumors; for instance, one of the largest studies has demonstrated that 1188 (9.9%) of 12,019 patients exhibited an MSI-high signature in various types of tumors [2]. However, there are no sufficient investigations on the MSI status in pediatric solid tumors, except those on limited tumor subtypes, including glioblastoma and medulloblastoma [3, 4]. Herein, we investigated the MSI status in pediatric patients with various solid tumors who died due to the tumor and also evaluated the potential of immune checkpoint inhibitors in refractory pediatric solid tumors.From April 2000 to May 2019, a total of 334 pediatric patients with solid tumors were admitted to the Nagoya University Hospital (Table 1 ). Although the majority of patients survived, 74 (22%) died, including 68 due to relapse or refractory tumor, 4 due to pulmonary complications after stem cell transplantations, and 2 due to infection after chemotherapies. We retrospectively analyzed the formalin-fixed paraffin-embedded tumor tissues of 40 (54%) of the 74 patients who died to assess the MSI status (Supplemental Table 1 , Supplemental Figure 1 ) using five multiplexed markers for determining the MSI-high phenotype (BAT-25, BAT-26, MONO-27, NR-21, and NR-24) (Supplemental methods ). Results demonstrated that 36 cases were microsatellite-stable and none of the patients had an MSI-high status; however, this observation could not be confirmed for the remaining four patients because of poor sample quality.These results indicate that MSI-high status is rare in pediatric patients with solid tumors who die of the disease. Therefore, surveillance of MSI status in children with refractory/relapsed solid tumors might have a limited role in predicting the responsiveness to immune checkpoint inhibitors.

We present a case of coronary artery bypass grafting in a 78-year-old man with triple vessel disease and concomitant cardiac amyloidosis. Postoperatively he developed a profound low cardiac output state and multi-organ failure. He died 3 weeks following surgery. Bypass surgery is rarely performed in patients with cardiac amyloidosis, and there is little in the literature regarding outcomes. The few published cases present a bleak picture, and hence percutaneous coronary intervention should always be preferred.

Background: Children with sickle cell disease (SCD) have higher resting basal metabolic rates than healthy peers and have historically been underweight. Current treatments increase patients’ hemoglobin (Hb) level and decrease reticulocytosis, which may in turn decrease patients’ basal metabolic rates. Objective: To examine the rates of overweight and obesity in children with SCD compared to state and national norms and to assess the correlation between Hb and weight status. Methods: We conducted a retrospective chart review of patients with SCD between the ages of 2-19 years from October 2013 until April 2019. Data were collected from the most recent clinic visit and Body Mass Index (BMI) percentiles were calculated using Center for Disease Control growth charts. Mississippi and national weight status estimates for youth 10-17 years were obtained from the 2016-2017 National Survey of Children’s Health. Results: Data were available for 787 patients. For children 10-17 years (n = 480), 24.5% of patients were overweight/obese compared to Mississippi and national rates, 39.2% and 31%, respectively. The prevalence of 10-17 year olds who were overweight (12.7%) was not significantly different from Mississippi (13.1%) or national (15.2%) (p = 0.13). Hb were different among patients who were underweight (8.80g/dL), normal weight (9.2g/dL), and overweight/obese (10.5g/dL) (p < 0.001). Conclusions: Children with SCD in Mississippi have similar rates of overweight compared to state and national norms and have higher Hb than patients with SCD who are normal weight/underweight. The impact of increased BMI in SCD is unknown and additional longitudinal studies are needed.

Objectives: Systemic steroids are a well-known, proven treatment for olfaction impairment. Topical nasal steroids are an attractive alternative that avoids systemic side effects and might provide an increased local drug activity. Nonetheless, the access of the medication to the olfactory cleft (OC) by using low- volume devices, such as nasal drops, is greatly dependent on the position of the head. We aimed to examine the accessibility of nasal drops to the OC area in two different head positions: the Mygind (lying head back) position and the Kaiteki position. Design and Setting: This is a cadaver study; the specimens were firstly positioned in Mygind and thereafter in Kaiteki positions. Nasal drops mixed with blue food dye were administered into the nostril in each head position. Endoscopic videos were recorded, and two blinded observers scored the extent of olfactory cleft penetration (OCP) using a 4-point scale (0 = none, 3 = heavy). Participants: Twelve fresh-frozen cadaver specimens Main outcome measures: The dye’s penetration to the OC Results: The mean score of nasal drops penetrance to the OC in the Mygind position was 1.34, as compared to 1.76 in the Kaiteki position. The difference in the OCP score between the two groups was not statistically significant (p>0.05) Conclusion: Both Mygind and Kaiteki head positions are reasonable alternatives in treatment with nasal drops for olfaction impairment. The preference of one position over another should rely on the patient’s comfort.

Objective: Suppurative acute thyroiditis is caused by pyriform sinus fistula (PSF), and PSF frequently elicits deep neck abscess. However, complete fistulectomy is the ideal management of PSF, and studies on surgical findings of PSF are exceedingly rare. This study aimed to reveal the origins of PSF, each route, and clinical presentation. Methods: This is a multicenter study. We have conducted 19 complete fistulectomies of PSF in Japan, analyzed routes of the fistulas, estimated the origins, and investigated their histological and clinical findings. Results: No recurrence was observed in all cases. Five of 12 cases showed thymic and/or parathyroid tissues around the fistulas, passing inside the inferior horn of thyroid cartilage, were regarded as having 3rd pouch origin, and tended to have low frequency of severe deep neck abscess. The remaining seven cases originated from the 4th pouch running outside of the horn and showed frequent severe infection. Conclusion: PSF have two different routes depending on their generation and may present different clinical manifestations.

To the Editor, The fermentation process, born as a preservation method in the Neolithic age, enabled humans to eat not-so-fresh food and to survive.1 Fermented foods are “foods or beverages made via controlled microbial growth (including lactic acid bacteria (LAB)) and enzymatic conversions of food components.” 2 Not all fermented foods contain live cultures, as some undergo further processing after fermentation: pasteurization, smoking, baking, or filtration. These processes kill or remove the live microorganisms in foods such as soy sauces, bread, most beers and wines as well as chocolate. Live cultures can be found in fermented vegetables and fermented milk (fermented sour milk, yoghurt, probiotics, …). The westernized diet is lacking many traditional fermented foods.3The gut microbiota has an inter-individual variability due to genetic predisposition and diet 3. Some foods like cabbage can be fermented by the gut microbiota. 4 The westernized diet has been associated with changes in the gut microbiome.5In this Rostrum, we consider loss of food fermentation either as a reduction of fermented food consumption in the diet or as a change in the microbiome leading to a reduction of fermentation of foods in the gut. This paper is based on the hypothesis that diet may partly explain differences in COVID-19 death rates within and between countries.6

Paravalvular leak (PVL) is a recognized and challenging complication after surgical or transcatheter valve replacement. The transcatheter closure of PVL has become the first-line treatment in clinical practice when the procedure is not contraindicated. Transcatheter PVL closure rests a complex procedure and complications still occur in approximately 9% of patients. We describe the case of a delayed mechanical prosthetic leaflet impingement after transcatheter closure of a paravalvular leak associated with a Valsalva pseudoaneurysm that required an urgent surgery. The transcatheter closure of PVL does not preclude subsequent attempt to surgical repair and outcome.

Background: The change of left ventricular function deteriorated with age because of gradual increases of blood pressure may result in increased energy loss (EL) in left ventricle (LV). The present study investigated EL in LV among hypertensive elderly patients and examined factors contributing to EL. Methods: A single-center retrospective study was performed on elderly hypertensive outpatients (65 years) who underwent echocardiography (N=105). EL in the LV was measured using an vector flow mapping system, and factors affecting peak EL during the early diastolic phase (ED-EL), late diastolic phase (LD-EL), and systolic phase (Sys-EL) were evaluated. Result: Mean age was 79.9±6.4 years (male 43%). Mean ED-EL, LD-EL, and Sys-EL were 42.1±46.7, 75.6±60.2, and 40.4±40.2 mJ/N/s. In a stepwise regression analysis, the E wave peak velocity of transmitral flow (unstandardized B=0.002, 95%CI 0.001 to 0.002, standardized β=0.547, p<0.001) and stroke volume in the LV outflow tract (LVOT) (B=0.001, 95%CI 0.000 to 0.001, β=0.190, p=0.034) were identified as factors affecting ED-EL. The factors affecting LD-EL were the E/A ratio (B=-0.122, 95%CI -0.180 to -0.064, β=-0.451, p<0.001) and peak velocity in LVOT (unstandardized B=0.001, 95%CI 0.0001 to 0.001, β=0.339, p=0.003). The factors influencing Sys-EL were peak velocity in LVOT (B=0.001, 95%CI 0.001 to 0.001, β=0.619, p<0.001) and the E/A ratio (B=-0.050, 95%CI -0.087 to -0.013, β=-0.241, p=0.008). Conclusion: Peak EL in the LV was higher during diastolic phase than systolic phase among elderly hypertensive patients. Peak EL during each phase was affected by systolic blood flow in LVOT and LV transmitral flow.