bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient Receptor Potential Vanilloid Type 1 Protects Against Pressure Overload–Induced Cardiac Hypertrophy by Promoting Mitochondria-Associated Endoplasmic Reticulum Membranes
Authors: Wang Yuxiang , Li Xiuchuan , Xu Xiaoli , Qu Xuemei , Yang Yongjian
Published: June 2022

Transient receptor potential vanilloid type 1 (TRPV1) is a nonselective cation channel that mediates the relationship between mitochondrial function and pathological myocardial hypertrophy. However, its underlying mechanisms remain unclear. This study aimed to investigate whether TRPV1 activation improves the morphology and function of intracellular mitochondria to protect cardiomyocytes after pressure overload-induced myocardial hypertrophy. The myocardial hypertrophy model was established by performing transverse aortic constriction surgery in C57BL/6 J male mice. The data revealed that TRPV1 activation significantly reduced myocardial hypertrophy, promoted ejection fraction% and fractional shortening%, and decreased the left ventricular internal diameter in end-diastole and left ventricular internal diameter in end-systole after transverse aortic constriction. Moreover, in vitro experiments revealed that TRPV1 reduces cardiomyocyte area and improves mitochondrial function by promoting mitochondria-associated endoplasmic reticulum membranes (MAMs) formation in a phenylephrine-treated cardiomyocyte hypertrophy model. TRPV1 up-regulates the phosphorylation levels of AMP-activated protein kinase and expression of mitofusin2 (MFN2). TRPV1 function is blocked by single-stranded RNA interfering with silent interfering MFN2. Activation of TRPV1 reduced mitochondrial reactive oxygen species caused by phenylephrine, whereas disruption of MAMs by siMFN2 abolished TRPV1-mediated mitochondrial protection. Our findings suggest that TRPV1 effectively protects against pressure overload-induced cardiac hypertrophy by promoting MAM formation and conserved mitochondrial function via the AMP-activated protein kinase/MFN2 pathway in cardiomyocytes.
Predictive Capacity of Population Pharmacokinetic Models for the Tacrolimus Dose Requirements of Pediatric Solid Organ Transplant Recipients
Authors: Pasternak Amy L. , Park Jeong M. , Pai Manjunath P.
Published: June 2022

Background:

Transplant recipients require individualized tacrolimus doses to maximize graft survival. Multiple pediatric tacrolimus population pharmacokinetic (PopPK) models incorporating CYP3A5 genotype and other covariates have been developed. Identifying the optimal popPK model is necessary for clinical implementation in pediatric solid organ transplant. The primary objective was to compare the dose prediction capabilities of the developed models in pediatric kidney and heart transplant recipients.

Methods:

Pediatric kidney or heart transplant recipients treated with tacrolimus and available CYP3A5 genotype data were identified. The initial weight-based tacrolimus dose and first therapeutic tacrolimus dose were collected retrospectively. Three published popPK models were used to predict the tacrolimus dose required to achieve a tacrolimus trough concentration of 10 ng/mL. Model dose predictions were compared with the initial and first therapeutic doses using Friedman test. The first therapeutic dose was plotted against the model-predicted dose.

Results:

The median initial dose approximately 2-fold lower than the first therapeutic dose for CYP3A5 expressers. The Chen et al model provided the closest estimates to the first therapeutic dose for kidney transplant recipients; however, all 3 models tended to underpredict the observed therapeutic dose. For heart transplant recipients, Andrews et al model predicted doses that were higher than the initial dose but similar to the actual therapeutic dose.

Conclusions:

Weight-based tacrolimus dosing appears to underestimate the tacrolimus dose requirements. The development of a separate popPK model is necessary for heart transplant recipients. A genotype-guided strategy based on the Chen et al model provided the best estimates for doses in kidney transplant recipients and should be prospectively evaluated.
Etiology and clinical characteristics of pediatric non-neoplastic posterior reversible encephalopathy: systematic review
Authors: Jordão Mariana , Raimundo Pedro , Jacinto Ruben , Garrido Daniel , Martins João , Estevens Rui , Nogueira Jerina , Fernandes Emanuel , Macedo Ana , Nzwalo Hipólito
Published: June 2022

Background:

Although more commonly seen in adult population, posterior reversible encephalopathy syndrome (PRES) can also be observed in pediatric patients. The etiopathogenesis of pediatric PRES is poorly understood, and the available evidence comes mostly from childhood cancer. Analysis of the sociodemographic and clinical characteristics of the different noncancer-related types can improve the understanding of pediatric PRES.

Methods:

Systematic review of characteristics and outcome of noncancer pediatric PRES. Primary sources of investigation were identified and selected through Pubmed and Scopus databases. The research was complemented by reference search in relevant publications. Study protocol was registered (Prospero CRD42020165798).

Results:

We identified 449 cases of noncancer pediatric PRES from 272 studies, median age 10 (newborn to 17 years), 49.9% girls. The 4 most common groups of conditions were renal 165 (36.7%), hematologic 84 (18.7%), autoimmune 64 (14.3%), and cardiovascular 28 (6.2%) disorders. The 4 most prevalent precipitants identified were hypertensive crisis 119 (26.5%), corticosteroids 56 (12.5%), immunosuppression drugs 44 (9.8%), and biologic drugs 14 (3.1%). Clinical presentations included seizures 100 (22.3%), headaches 22 (4.9%), encephalopathy 17 (3.8%), visual disturbances 6 (1.3%), and focal deficit 3 (0.7%). The distribution of lesions was (n = 380): combined anterior/posterior circulation (40.8%), isolated posterior circulation (24.1%), anterior circulation (6.2%), and deep structures (1.6%). Residual neurological deficits occurred in about 1 out 10 cases.

Conclusion:

Pediatric PRES differs from the adult in etiology, precipitants, and clinical manifestations. Renal diseases predominate, acute raised blood pressure is less frequent, and cortical deficits are rarer. In addition, the proportion of patients with combined anterior/posterior circulation was higher. Permanent neurological sequels can occur.
Vitamin D levels in a population from Argentina with metabolic disorders
Authors: Luciardi Maria Constanza , Alemán Mariano Nicolás , Martinez Daniela , Maxzud Mirta Centeno , Soria Analía , Aldonati Mirta Ester , Luciardi Hector Lucas
Published: June 2022

Background:

Metabolic disorders are a public health problem worldwide. The vitamin D status in patients with metabolic diseases is not a routine procedure. The aim of this study was to determine the prevalence of vitamin D deficiency and examine the correlation between vitamin D status and cardiometabolic parameters in Latin American population with metabolic disorders.

Methods:

This observational study with a cross-sectional design included 151 patients with metabolic disorders (type 2 diabetes, hypothyroidism, type 2 diabetes with hypothyroidism, and excess weight). A fasting blood sample was collected and analyzed to determine the levels of 25-hydroxyvitamin D, calcium, glucose, hemoglobin A1c, thyroid-stimulating hormone, and free thyroxine. Anthropometric and blood pressure measurements were also performed.

Results:

According to vitamin D values established by the Institute of Medicine, subjects with metabolic disorders group showed: 23% risk to bone health (9.42 ±3.O4ng/mL), 45% risk of insufficiency/deficiency (17.05 ±2.12ng/mL), and 32% had sufficient levels (26.34±6.74ng/mL), whereas healthy subjects group showed significantly higher values than metabolic diseases group (37.25± 7.72). In addition, vitamin D levels were inversely correlated with elevated body mass index (29.13±5.15kg/m2), systolic blood pressure (126.50± 15.60 mm Hg), fast blood glucose (106.29±33.80 mg/dL), and hemoglobin A1c (6.40% ± 1.38%) values.

Conclusion:

Subjects with metabolic disorders and with adequate nutritional intake of vitamin D-rich foods and frequent exposure to sunlight have low serum vitamin D concentrations compared to the general population and vitamin D status should be assessed in these patients.
Health-related quality of life 6 years after bariatric surgery: factors influencing outcome
Authors: Soares Caroline , Pinho André Costa , Sousa Hugo Santos , da Costa Eduardo Lima , Preto John ,   CRI-O group
Published: June 2022

Purpose:

Bariatric surgery is the only proven treatment to significantly improve obesity and its associated comorbidities. The success of bariatric surgery goes beyond weight lost: quality of life (QoL) is acquiring relevance when evaluating outcomes after bariatric surgery but few studies evaluated factors influencing QoL at long term. The main objective of this study is to identify factors that could affect QoL more than 5 years after bariatric surgery.

Methods:

We performed an observational study in which we apply “Moorehead-Ardelt Quality of Life Questionnaire” to 94 patients that were submitted to bariatric surgery with more than 5years of follow-up. Patients questionnaire score was compared to several variables: age, sex, main surgical procedures, primary or revisional surgery, complications, weight loss, and improvement of comorbidities (diabetes, dyslipidemia, hypertension, musculoskeletal disorders, and psychiatry pathology).

Results:

QoL was significantly influenced by weight loss outcomes (%excess weight loss, %total weight loss, and final body mass index). QoL was neither significantly influenced by sex or age, type of surgery nor previously failed bariatric surgeries or complications. Improvement of hypertension was related to increased QoL, but improvement of other associated comorbidities did not had significant impact on patient’s QoL at long term.

Conclusion:

It appears that the main factors influencing long-term QoL after bariatric surgery are related to weight loss outcomes.
Improving quality of family life among Christian parents of children with low vision in Nsukka catholic diocese using rational emotive family health therapy
Authors: Uzodinma Uchenna Eugenia , Ede Moses Onyemaechi , Dike Ibiwari Caroline , Onah Nkechi G. , Obiweluozo Patience Enuma , Onwurah Chimezie N. , Onuorah Adaorah R. , Ejiofor Juliana Ngozi , Ugwu Collins Ikenna , Amoke Chijioke V. , Onah Sebastian O. , Diara Benjamin C. , Okwor Christopher O. , Aneke Olunwa Anthonia , Ngwoke Anthonia N. , Ezema Luke Chizoba , Ifelunni Clara Odozi , Nwachukwu Ugwunna C. , Oforka Theresa O. , Ilechukwu Leonard C.
Published: June 2022

Background:

Most Christian parents living with children with low vision have reported to be experiencing psychological disturbances that are affecting the family health. As a result, the quality of family life is being impaired. The experience of parents catering for children with low vision is mainly influenced by psychosocial factors that could determine the quality of family life of such parents. This present study is to investigate the efficacy of rational emotive family health therapy in reducing poor quality of family life among Christian parents of children with low vision in Nsukka Catholic Dioceses.

Method:

This is a randomized pretest and posttest control trial. Participants were 88 parents of children living with low vision in Nsukka Catholic Dioceses, Nigeria. The power of the sample size was determined using Gpower statistical software. The participants in rational emotive family health therapy programme-group were exposed to a 12-session treatment programme whereas their counterparts in waitlisted control group did not receive anything. A family quality of life scale was utilized in assessing the participants. Data analyses were performed using repeated measures ANOVA.

Results:

It was found that rational emotive family health therapy had a significant positive effect on increasing quality of family life among the study participants compared to those in the waitlisted control group.

Conclusion:

This study contributed and validated the efficacy of rational emotive family health therapy in improving quality of family life among parents of children with low vision.
Case fatality rate of the adult in-patients with COVID-19 and digestive system tumors
Authors: Wang Guoqun , Pan Lanlan , Zhao Jianyi , Tang Jie , Fang Yueyu , Sun Hui , Seesaha Poshita Kumari , Chen Wensen , Chen Xiaofeng
Published: June 2022

Background:

During the coronavirus disease 2019 (COVID-19) pandemic, endoscopic screening for gastrointestinal tumors was suspended or delayed in most countries. Thus, our study aimed to quantify the impact of COVID-19 on the clinical outcomes of patients with digestive system tumors through a systematic review and meta-analysis.

Methods:

We systematically searched the PubMed, Web of Science, Cochrane Library, and Embase databases as of March 7, 2021 to identify the case fatality rate (CFR) of COVID-19 patients diagnosed with digestive system tumors. A random-effects model was used for meta-analysis, I
2 was used to assess heterogeneity, and funnel plot was used to assess publication bias.

Results:

A total of 13 studies were included, involving 2943 tumor patients with COVID-19, of which 871 were digestive system tumors, and the CFR was 24% (95% CI, 18%–30%; I
2 = 55.7%). The mortality rate of colorectal cancer was 21% (95% CI, 14%–27%; I
2 = 0.0%), gastric cancer was 25% (95% CI, 6%–45%; I
2 = 0.0%), and hepatobiliary cancer was 29%. In general, there was no significant difference in the CFR of digestive system tumors.

Conclusion:

The combined CFR of digestive system tumors and COVID-19 patients was 24%, which is much higher than that of the general population. Under the premise of fully complying with the international guidelines to limit the spread of COVID-19, we call for the resumption of endoscopic screening programs and selective surgery as soon as possible.

Registration information:

PROSPERO registration no. CRD42021248194.
Adjuvant therapy for HER2 positive pT1a-b pN0 breast cancer
Authors: Yang Xuan , Qu Chong Xiao
Published: June 2022

Deciding if patients with small (≤1 cm), node-negative, human epidermal growth factor receptor 2 (HER2) positive breast cancer should receive adjuvant systemic therapy remains a challenge. No randomized clinical trials have examined the efficacy of trastuzumab in this setting. This prospective observational study aimed to investigate the choice of adjuvant systemic therapy in clinical practice in China.

We prospectively collected data from patients with HER-2 positive breast cancer (less than 1 cm and node negative) patients who underwent breast cancer surgery at Shanxi Provincial People's Hospital Breast Center from January 1, 2017 to December 31, 2019, and retrospectively investigated the association between baseline clinicopathological features and treatment strategy, cardiotoxicity, and disease outcome.

Of 168 eligible patients, 102 (60.7%) received adjuvant systemic therapy with trastuzumab (AST+T), 47 (28%) received adjuvant systemic therapy without trastuzumab (AST) and 19 (11.3%) did not receive adjuvant systemic therapy. Multivariate logistic regression analysis demonstrated that age, tumor size and hormone receptor status were significantly associated with treatment choice. Three-year invasive disease-free survival probability was 100%, 97.9% and 89.5% with AST+T, AST, and no therapy, respectively (P < .001).

The majority of patients (60.7%) with pT1a-b pN0 HER2 positive breast cancer received adjuvant systemic therapy with trastuzumab, whereas only 11.3% did not receive any adjuvant systemic therapy. Tumor size, age and hormone receptor status influenced treatment choice. The 3-year invasive disease-free survival probability was significantly higher for patients who received adjuvant systemic therapy with trastuzumab compared with those who did not receive adjuvant systemic therapy. Cardiac adverse events were rare.
Associations of health-related quality of life with depression and stigma in MERS-CoV survivors during the recovery period
Authors: Ahn So-Hyun , Kim Jeong Lan , Lee So Hee , Park Hye Yoon , Lee Jung Jae , Lee Haewoo
Published: June 2022

We explored factors related to health-related quality of life (HRQOL), including psychiatric symptoms and stigma related to Middle East respiratory syndrome coronavirus (MERS-CoV) infection, among MERS-CoV survivors during the recovery period.

Sixty-three MERS-COV survivors were recruited from five hospitals for a cohort study, one year after their infection in 2015. The subjects’ demographic information and medical conditions associated with MERS-CoV were recorded. HRQOL was evaluated using the Short Form-8 Health Survey (SF-8). Depression, post-traumatic stress symptoms, chronic fatigue, and perceived stigma were assessed using several questionnaires

The mean physical component summary (PCS) and mean mental component summary (MCS) of the SF-8 score were below 50 T (43.47 ± 9.60, 45.74 ± 10.18). Depression, chronic fatigue, posttraumatic stress symptoms and stigma were negatively correlated with the SF-8 PCS and MCS. Multivariate logistic regression analysis showed that the PCS was associated with stigma (OR 8.66, 95% CI 1.96–38.23), whereas MCS was associated with depression (OR 26.62, 95% CI 3.56–198.85).

The estimated HRQOL of MERS-CoV survivors during recovery was poor and appeared to be associated with depression and MERS-related stigma.
Physiological exophoria did not increase the incidence of myopia in rural school children in Taiwan
Authors: Hsu Jui-Hung , Lai Li-Ju , Tung Tao-Hsin , Hsu Wei-Hsiu
Published: June 2022

This study evaluated the incidence rate and risk factors for developing myopia in elementary school students in Chiayi, Taiwan. This prospective cohort study comprised 1816 students without myopia (grades 1 to 5 in Chiayi County). The students underwent a noncycloplegic ocular alignment examinations using an autorefractometer and completed a questionnaires at baseline and at a 1-year follow-up. A univariate logistic regression was used to assess the effects of the categorical variables on new cases of myopia. A multinomial logistic regression was then conducted. A chi-squared test was used to compare new cases of myopia in terms of ocular alignment. A Cox hazard ratio model was then used to validate factors associated with changes in ocular alignment. A P value of <.05 was considered significant. In 370 participants with new cases of myopia out of 1816 participants, a spherical error of −1.51 ± 0.6 diopters was noted at follow-up. The baseline ocular alignment was not a significant risk factor for developing myopia (exophoria vs orthophoria: OR 1.26, 95% CI 0.97–1.62; other vs. orthophoria: OR 1.15, 95% CI 0.73–1.82). However, new cases of myopia (HR 1.36, 95% CI 1.14–1.61), and baseline ocular alignment (exophoria vs orthophoria: HR 3.76, 95% CI 3.20–4.42; other vs orthophoria: HR 3.02, 95% CI 2.05–4.45) were associated with exophoria at follow-up. This study provided epidemiological data on the incidence of myopia in elementary school students in Chiayi, Taiwan. It also demonstrated that physiological exophoria does not predispose patients to developing myopia.
Clinical significance of HEp-2 cell cytoplasmic patterns in anti-neutrophil cytoplasmic antibody associated vasculitis
Authors: Zhang Naidan , Ji Chaixia , Bao Xiao , Yuan Chengliang
Published: June 2022

The study was to investigate the clinical characteristics and significance of antinuclear antibody (ANA) cytoplasmic patterns in ANCA-associated vasculitis (AAV) from Southwest China.

A retrospective study including 232 AAV patients from Peoples Hospital of Deyang City was performed. These included 115 patients with ANA cytoplasmic pattern as observation group and 117 patients without ANA cytoplasmic pattern as control group.

Chest involvement (60.00 vs 46.15, P = .035), cardiovascular involvement (5.21 vs 29.91, P < .001), and renal involvement (37.39 vs 77.78, P = .001) were different between groups.

Total protein (69.55 vs 64.01, P < .001), triglyceride (1.41 vs 1.18, P = .023), mean cell volume (89.76 vs 87.59, P = .040), and estimated glomerular filtration rate (76.67 vs 50.87, P = .035) were higher in ANA cytoplasmic patterns group. Creatinine (73.00 vs 117.50, P = .011), white blood cell (6.93 vs 8.86, P = .001), platelet (196.0 vs 239.0, P = .017), anti-myeloperoxidase (2.44 vs 3.42, P = .042), and anti-proteinase 3 (1.00 vs 4.93, P = .007) were lower in this group. In multivariate analysis, creatinine (odds ratio [OR] = 1.21, 95% confidence interval [CI]: 1.06–1.38), triglyceride (OR = 1.97, 95% CI: 1.10–3.48), and anti-myeloperoxidase (OR = 1.64, 95% CI: 1.37–1.95) were independent risk factors of AAV renal involvement. Total protein (OR = .95, 95% CI: 0.91–0.99) was an independent protective factor of AAV renal involvement. Chi-square test showed that speckled pattern was different among anti-neutrophil cytoplasmic antibody patterns (χ
2 = 18.526, P < .001).

In summary, HEp-2 cell cytoplasmic patterns have certain clinical significance in AAV, which is a new exploration of the clinical value of ANA.
Retrospective analysis of hepatic perivascular epithelioid cell tumour (PEComa) in a single centre for clinical diagnosis and treatment clinical diagnosis and treatment of hepatic PEComa
Authors: Yang Xiao , Wang Qingyuan , Zhou Xiao , Zhou Haoming , Jia Wenbo , Hu Chunyang , Chu Jian , Kong Lianbao
Published: June 2022

Our primary objective was to investigate the clinical features, diagnosis, treatment and prognosis of hepatic perivascular epithelioid cell tumour (PEComa).

Thirty-five cases of pathologically proven hepatic PEComa that were treated in the Department of Hepatobiliary Centre of the First Affiliated Hospital of Nanjing Medical University from January 2008 to February 2019 were retrospectively analysed, and the literature was also reviewed.

Twenty-nine females and 6 males were included in this study. The mean age of these patients was 48.0 years (range, 21–75 years). Thirteen patients complained of upper abdominal pain or discomfort, while others were accidentally discovered by imaging examination. Hepatic PEComas tended to occur in the right lobe of the liver (20 cases in the right lobe, 13 in the left lobe and 2 in the caudate lobe). Two cases were characterized by multiple tumours, and the remaining cases were single lesions (range, 1.2–12 cm). Only 8 cases were correctly diagnosed by the preoperative imaging examination, and the correct diagnosis rate was only 22.9%. The postoperative immunohistochemistry analysis showed that hepatic PEComas are positive for human melanoma black 45, Melan-A and smooth muscle actin, with the exception of 1 case that was negative for Melan-A. All patients undergoing an operation accepted regular follow-up, and the average time was 66.5 months (range, 3–132 months). Two patients who experienced tumour recurrence and 1 patient who died of cardiovascular disease, but the remaining patients showed no evidence of tumour recurrence or metastasis during the follow-up period.

Hepatic PEComas are a rare type of tumours that mainly occur in young and middle-aged women. The lack of clinical manifestations and imaging findings increases the difficulty of determining a preoperative diagnosis, which mainly depends on the results of pathological examinations. Surgery is currently the only effective treatment, and long-term clinical follow-up is necessary due to the aggressive behaviour and relapse of hepatic PEComa in some patients.
Segmented linear correlations between bone scan index and prostate cancer biomarkers, alkaline phosphatase, and prostate specific antigen in patients with a Gleason score ≥7
Authors: Ebrahim Tasmeera , Hadebe Bawinile , Aldous Colleen , Tinarwo Partson , Nyakale Nozipho
Published: June 2022

Technetium-99m methyl diphosphonate bone scintigraphy is relatively easily accessible for detecting bone metastases in prostate cancer patients. However, it is subjective and can be challenging to compare images taken at different time points. The bone scan index (BSI) is a more objective evaluation and allows for better comparison of images. Its correlation with other biomarkers of prostate cancer metastases such as prostate specific antigen (PSA) and alkaline phosphatase (ALP) is not clearly understood. This study thus aimed to compare the BSI correlation to PSA against that of BSI to ALP levels in patients with a Gleason score ≥7.

A retrospective analysis of the medical records of 50 prostate cancer patients with a Gleason score of ≥7 referred for a bone scan between January 1, 2015 and December 31, 2018 was undertaken. Bone scans were interpreted visually, and using a semi-automated computer programme to quantify the BSI and its relation to PSA and ALP measurements.

For the metastasis positive measurements, there was a statistically significant moderate positive overall linear correlation between BSI and PSA. For ALP and BSI, there were 2 segmented strong positive linear relationships between them. The first segment consisted of ALP < 375 IU/L and BSI >10%, where ALP and BSI were strongly and positively correlated. The other segment tended to have generally low BSI measurements (<10%) and also had a strong and positive correlation.

The BSI was found to be better linearly correlated with ALP than PSA.
Long-term outcomes after different treatments for gastric cancer with synchronous liver metastasis
Authors: Li Minghui , Yang Bin
Published: June 2022

Background:

The treatment of gastric cancer (GC) with synchronous liver metastasis is still controversial. This systematic review and network meta-analysis was designed to evaluate the long-term outcomes after different treatments of GC with synchronous liver metastasis.

Methods:

Several electronic databases were searched to identify eligible studies updated on May 1, 2021. Studies assessing the overall survival (OS) after different treatments (including chemotherapy, interventional therapy, surgical therapy alone and adjunctive therapy after surgery) of GC with synchronous liver metastasis were included. Odds ratios with 95% confidence interval (CI) were calculated for survival variables.

Results:

A total of 15 studies including 4312 patients were included in this network meta-analysis. Adjunctive therapy after surgery performed better than surgery therapy alone (hazard ratio [HR] = 1.23, 95% credible interval [CrI]: 0.69–2.17), chemotherapy (HR = 1.18, 95%CrI: 0.71–1.95), and interventional therapy in terms of 1-year OS (HR = 2.03, 95%CrI: 1.22–3.37). In terms of 3-OS, adjunctive therapy after surgery showed better efficacy than surgery therapy alone (HR = 1.48, 95%CrI: 0.40–5.47), chemotherapy (HR = 1.27, 95%CrI: 0.37–4.35), and interventional therapy (HR = 3.16, 95%CrI: 0.73–13.63). For 5-OS, adjunctive therapy after surgery was superior to surgery therapy alone (HR = 1.74, 95%CrI: 0.08–37.76), chemotherapy (HR = 1.44, 95%CrI: 0.66–3.14), and interventional therapy (HR = 1.46, 95%CrI: 0.06–34.36). There were no statistical inconsistency and small-study effect existed in our network meta-analysis for 1-year, 3-year, or 5-year OS. Cluster ranking analysis performed with surface under the cumulative ranking showed adjuvant therapies after surgery (99.9, 96.7, 90.2) ranking higher than surgery therapy alone, chemotherapy, and interventional therapy for 1-year, 3-year, 5-year OS.

Conclusion:

The OS of adjuvant therapy after surgery was better than that of surgery therapy alone, chemotherapy, and interventional therapy. Adjuvant therapy after surgery is the most recommended therapy for people with GC with synchronous liver metastasis.
ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease
Authors: Mearin Maria Luisa , Agardh Daniel , Antunes Henedina , Al-toma Abdul , Auricchio Renata , Castillejo Gemma , Catassi Carlo , Ciacci Carolina , Discepolo Valentina , Dolinsek Jernej , Donat Ester , Gillett Peter , Guandalini Steffano , Husby, MD, DMSc Steffen , Koletzko, MD Sibylle , Koltai Tunde , Korponay-Szabó Ilma Rita , Kurppa Kalle , Lionetti Elena , Mårild Karl , Martinez Ojinaga Eva , Meijer Caroline , Monachesi Chiara , Polanco Isabel , Popp Alina , Roca Maria , Rodriguez-Herrera Alfonso , Shamir Raanan , Stordal Ketil , Troncone Riccardo , Valitutti Francesco , Vreugdenhil Anita , Wessels Margreet , Whiting Penny ,   on behalf of the ESPGHAN Special Interest Group on Celiac Disease
Published: June 2022

There is a need for consensus on the recommendations for follow-up of children and adolescents with celiac disease.

Objectives:

To gather the current evidence and to offer recommendations for follow-up and management.

Methods:

The Special Interest Group on Celiac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essential for follow-up care. A literature search (January 2010–March 2020) was performed in PubMed or Medline. Relevant publications were identified and potentially eligible studies were assessed. Statements and recommendations were developed and discussed by all coauthors. Recommendations were voted upon: joint agreement was set as at least 85%.

Results:

Publications (n = 2775) were identified and 164 were included. Using evidence or expert opinion, 37 recommendations were formulated on: The need to perform follow-up, its frequency and what should be assessed, how to assess adherence to the gluten-free diet, when to expect catch-up growth, how to treat anemia, how to approach persistent high serum levels of antibodies against tissue-transglutaminase, the indication to perform biopsies, assessment of quality of life, management of children with unclear diagnosis for which a gluten-challenge is indicated, children with associated type 1 diabetes or IgA deficiency, cases of potential celiac disease, which professionals should perform follow-up, how to improve the communication to patients and their parents/caregivers and transition from pediatric to adult health care.

Conclusions:

We offer recommendations to improve follow-up of children and adolescents with celiac disease and highlight gaps that should be investigated to further improve management.
SARS-CoV-2 Infection in Pediatric Solid Organ Transplant Recipients: A Single Center Observation
Authors: Paul Saikat , Royal Scott , Lee Margaret , Shin Stephanie , Chahine Joeffrey , Rozeboom Aaron , Ahn Jaeil , Dhani Harmeet , Yazigi Nada , Kaufman Stuart , Khan Khalid , Matsumoto Cal , Kroemer Alexander , Fishbein Thomas , Ekong Udeme D.
Published: June 2022

Objectives:

This is a descriptive study to characterize rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pediatric solid organ transplant (SOT) recipients during the early days of the pandemic. We hypothesized that asymptomatic infection may represent a large proportion of SARS-CoV-2 infection in pediatric SOT recipients.

Methods:

We queried Organ Transplant Tracking Record (OTTR) for all pediatric SOT recipients followed at our center and reviewed medical records to identify patients tested for SARS-CoV-2 between March 15, 2020 and June 30, 2021. Patients were tested by polymerase chain reaction (PCR): prior to planned procedures or because of symptoms; OR: tested by measurement of IgG to spike protein with their routine labs q 2-monthly. A positive PCR was called acute infection. A positive IgG with negative PCR was called convalescence. For immunologic studies, blood was obtained when the PCR or IgG was positive. Statistical comparisons were made between (1) acute infection versus convalescence; (2) acute infection versus SOT recipients without infection (called healthy controls); (3) liver transplant (LT) versus small bowel (SB)/multivisceral transplant (MVT); (4) positive versus negative test result.

Results:

Of 257 LT recipients, 99 were tested: 6 were PCR positive, 13 were antibody positive. Of 150 SB/MVT recipients, 55 were tested: 4 were PCR positive, 6 were antibody positive. Of 8 simultaneous liver, kidney transplant recipients, 3 were tested: 1 was PCR positive. Symptoms when present were mostly mild. Patients with a positive test result were younger (6.3 vs 10.0 years; P = 0.017). We observed a rapid decline in viral load within 96 hours without a change in immunosuppression. Antibody lasted >8 months beyond the time it was monitored. Acute infection was associated with increased CD4 and CD8 TEM cell frequency (P = 0.04, P = 0.03, respectively), decreased interferon (IFN)-γ production from T-cells (2.8% vs 11.3%; P = 0.006), and decreased CD8 TEMRA frequency (4.56% vs 11.70%; P = 0.006).

Conclusions:

Early in the pandemic, COVID-19 disease was mostly mild in pediatric SOT recipients with no rejection, patient death, or graft loss observed.
Adipose-derived stem cell-enriched lipotransfer reverses skin sclerosis by suppressing dermal inflammation
Authors: Jiang Wenqing , Wang Jing , Lin Jiayan , Jiang Shenglu , Quan Yuping , Liao Yunjun , Gao Jianhua , Cai Junrong
Published: June 2022

Background:

Scleroderma is a chronic autoimmune disease with an incidence of 2.7 per 100,000 people. Traditional lipotransfer has been used to treat atrophic sclerotic skin. Enzymatically processed cell-assisted lipotransfer (CAL) and mechanically processed stromal vascular fraction gel (SVF-gel) are fat products with abundant adipose-derived stem cells (ASCs). The present study aimed to assess whether ASC-enriched lipotransfer elicits superior therapeutic effects on scleroderma.

Methods:

Scleroderma was induced in nude mice by injections of bleomycin for 4 weeks. Human-derived Coleman fat (CF), CAL, or SVF-gel (0.1 mL) was injected into sclerotic lesions. Histologic examinations, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and expression analyses of inflammatory factors in skin lesions and transferred fat were performed at 4 weeks post-implantation.

Results:

Dermal thickness was lower in the CF- (339.0 ± 19.66 µm), CAL- (271.0 ± 16.15 µm), and SVF-gel- (197.8 ± 12.99 µm) injected groups than in the phosphate-buffered saline-injected group (493.3 ± 28.13 µm) (P<0.05). The numbers of TUNEL+ and Mac2+ cells in fat tissue were significantly higher in the CF-injected group than in the SVF-gel- and CAL-injected groups. Expression of monocyte chemotactic protein-1 and interleukin-6 was significantly lower in the ASC-enriched groups than in the CF group. Histologic analysis showed there were far fewer macrophages and myofibroblasts in skin lesions in the ASC-enriched groups than in the CF group.

Conclusion:

Transplantation of SVF-gel and CAL, which contain abundant ASCs, reduces the levels of apoptotic cells and inflammation, significantly reverses skin sclerosis, and elicits superior anti-inflammatory and anti-fibrotic effects on scleroderma.
Malignant Gastrointestinal Neuroectodermal Tumor: A New Kid on the Block?
Authors: Morani Ajaykumar C. , Ramani Nisha S. , Yedururi Sireesha , Prasad Srinivasa R.
Published: June 2022

Also referred to as “osteoclast-rich, clear cell sarcoma–like tumor of the gastrointestinal tract (CCSLGT),” malignant gastrointestinal neuroectodermal tumor is a newly described, rare, aggressive sarcoma that commonly arises in the small bowel, stomach, and colon. Histogenesis is likely from an autonomous nervous system–related primitive cell of neural crest origin. The hallmark genetic finding of EWS-CREB1 or EWS-ATF1 fusion transcripts clinches the diagnosis. Annular constrictive lesions tend to be smaller, show homogenous contrast enhancement on computed tomography, and may present with bowel obstruction. Larger, expansile masses tend to be exophytic and show heterogeneous contrast enhancement. Surgical resection is the mainstay of treatment. Frequent recurrences, metastases, and death from disease in 75% of patients portend a poor prognosis. Targeted chemotherapy based on specific tumor pathways is being developed.
Frontofacial Reconstruction Technique Modification With Preservation of Blood Supply to the Monobloc Segment
Authors: King Brody , Veith Jacob , Kim Erinn , Kestle John , Siddiqi Faizi , Gociman Barbu
Published: June 2022

Craniosynostosis syndromes, including Apert Syndrome, Pfeiffer Syndrome, and Crouzon Syndrome, share similar phenotypes, including bicoronal craniosynostosis, midface hypoplasia, hypertelorism, and exorbitism. The standard surgical treatment for these craniofacial abnormalities is monobloc osteotomy with distraction osteogenesis. Complications of this technique include the failure of osteogenesis or resorption of the frontal bone. The authors propose an alternative surgical technique with a frontal arch in continuity with the midface segment to ensure vascularization to anterior and posterior borders of distraction. A case report of an 8-year-old female patient with Apert Syndrome is reported using our technique. Our frontal arch monobloc distraction procedure preserves blood supply to a cranial component of the monobloc segment site that becomes the anterior portion of distraction rather than with the traditional devascularized frontal bone flap. This technique modification should improve osteogenesis outcomes by preventing resorption or failure of bone formation.
The Effects of Preoperative Administration of Erythropoietin in Pediatric Patients Undergoing Cranial Vault Remodeling for Craniosynostosis
Authors: Chumble Ameya , Brush Parker , Muzaffar Arshad , Tanaka Tomoko
Published: June 2022

Background and Purpose:

Over 90% of patients undergoing cranial vault remodeling for craniosynostosis receive blood transfusions to compensate for intraoperative blood loss. However, transfusions are not without risk and can lead to allergic and immune transfusion reactions as well as rare cases of infectious transmissions. Preoperative use of erythropoietin in cranial vault remodeling has been demonstrated to be safe and to reduce transfusion requirements in prior studies. This study’s purpose is to add to the body of data supporting the safe use of a protocolized erythropoietin alfa regimen before cranial vault remodeling and strip craniectomy procedures with decreased blood transfusion requirements and other favorable outcomes.

Methods:

A retrospective chart review was performed on patients who underwent cranial vault remodeling between 2006 and 2021 at our tertiary care center. Two groups were identified: in the first, preoperative erythropoietin was administered under protocol; and in the second, preoperative erythropoietin was not administered. The groups were compared with respect to age, perioperative hemoglobin levels, estimated blood loss during surgery, packed red blood cell transfusion volume, length of hospital stay, and length of surgery.

Results:

Demographics were not significantly different in terms of age, weight, diagnosis, gender, and type of procedure. Patients who were administered preoperative erythropoietin were found to have significantly increased preoperative hemoglobin levels (13.6 versus 12.3 g/dL), as well as decreased estimated intraoperative blood loss (376 versus 1099 mL), the volume of packed red blood cells transfused (316 versus 897 mL), length of hospital stay, and length of surgery. Postoperative hemoglobin levels were not found to be significantly different.

Conclusions:

In this study, preoperative administration of erythropoietin with elemental iron was beneficial for patients undergoing cranial vault remodeling for craniosynostosis. Specifically, it decreased the need for red blood cell transfusion, intraoperative blood loss, and length of hospital stay. No adverse events were recorded in the treatment arm. Further studies may include a separate group administered iron alone.
Selepressin in Septic Shock
Authors: Antonucci Elio , Giovini Manuela , Agosta Sara , Sakr Yasser , Leone Marc
Published: June 2022

Sepsis and septic shock usually show a high mortality rate and frequently need of intensive care unit admissions. After fluid resuscitation, norepinephrine (NE) is the first-choice vasopressor in septic shock patients. However, high-NE doses are associated with increased rates of adverse effects and mortality. In this perspective, many authors have proposed the administration of non-adrenergic vasopressors (NAV). Selepressin is a selective vasopressin type 1A (V1A) receptor agonist and may be a valid option in this field, because it can decrease NE requirements and also limit the deleterious effects induced by high doses of catecholamines. Only few clinical data actually support selepressin administration in this setting. Here, we review the current literature on this topic analyzing some pathophysiological aspects, the rationale about the use of NAV, the possible use of selepressin differentiating animal, and human studies. Various issues remain unresolved and future trials should be focused on early interventions based on a multimodal activation of the vasopressive pathways using both alpha and V1A receptors pathways.
Necroptosis, Pyroptosis, Ferroptosis in Sepsis and Treatment
Authors: Qu Mengdi , Wang Yanghanzhao , Qiu Zhiyun , Zhu Shuainan , Guo Kefang , Chen Wankun , Miao Changhong , Zhang Hao
Published: June 2022

As a global major health problem and a leading cause of death, sepsis is defined as a failure of homeostasis, which is mainly initiated by an infection and followed by sustained excessive inflammation until immune suppression. Despite advances in the identification and management of clinical sepsis, morbidity, and mortality remain high. In addition, clinical trials have failed to yield promising results. In recent years, the mechanism of regulated cell death (RCD) in sepsis has attracted more and more attention, because these dying cells could release a large number of danger signals which contribute to inflammatory responses and exacerbation of sepsis, providing a new direction for us to make treatment strategy. Here we summarize mechanisms of several forms of RCD in sepsis including necroptosis, pyroptosis, ferroptosis. In conclusion, targeting RCD is considered a promising approach to treat sepsis.
Health Care Disparities Among Latina Patients Presenting With Pelvic Organ Prolapse
Authors: Douglass K. Marie , Grisales Tamara , Coca Natalie , Tandel Megha D. , Kwan Lorna , Wieslander Cecilia
Published: June 2022

Importance

This study identifies barriers, including language and insurance status, Latina patients may face in accessing urogynecology care.

Objective

The aim of the study was to determine differences in objective prolapse severity at the time of presentation between Latina and non-Latina patients and the effect socioeconomic disparities may have on these differences.

Study Design

This is a retrospective cohort study of patients visiting urogynecology clinics at 2 academic institutions (1 private, 1 public). Patients with symptomatic > stage II prolapse were included. Initial Pelvic Organ Prolapse Quantification examinations, leading edge of prolapse, and demographic data were extracted. We evaluated several socioeconomic factors for associations with prolapse severity in a multivariable analysis.

Results

Three hundred forty-two patients were included (36% Latina). Twenty-eight percent were non-English speaking and 54% had public or no insurance. Using leading edge as the outcome, there was no objective difference in prolapse severity between the Latina and non-Latina patients. A higher proportion of patients with public insurance had more advanced prolapse compared with those with private insurance (odds ratio, 2.78; 95% confidence interval, 1.40–5.55; P < 0.01) and a higher proportion of non-English speaking had more advanced prolapse compared with English speakers (odds ratio, 2.44; 95% confidence interval, 1.12–5.34; P = 0.03).

Conclusions

Latina ethnicity was not a risk factor for more advanced prolapse at the time of initial evaluation in a urogynecology clinic. Rather, patients who were non-English speaking and had public insurance were more likely to present with more advanced prolapse. Our data suggest that language barriers and lower socioeconomic status are health care disparities for patients seeking care for prolapse.
Centering Group Treatment for Women With Interstitial Cystitis/Bladder Pain Syndrome: A Qualitative Analysis
Authors: Meriwether Kate Vellenga , Panter Virginia , McWethy Magdalena , Rishel Brakey Heidi , Komesu Yuko M.
Published: June 2022

Importance

Women with interstitial cystitis/bladder pain syndrome (ICBPS) face challenging treatment and feelings of isolation. Centering models of group medical visits have been successful in other spheres but have not been explored in ICBPS therapy.

Objective

We sought to describe opinions of women with ICBPS regarding Centering visits, including advantages, experience, and barriers to participation and efficacy.

Study Design

Patients who attended Centering visits participated in a focus group and/or filled out written commentary in evaluations, and control patients were individually interviewed. We coded transcripts using NVivo software for emergent themes.

Results

We conducted 4 control patient individual interviews, had one focus group of Centering patients, and collected comments from 34 post-Centering surveys. Emergent themes of interest included motivations and barriers to joining, cost, leadership, connecting with others, diversity, learning, alternative treatments, and areas for improvement. Regardless of participation in Centering, patients noted the importance of self-care and sharing with other women with ICBPS, and they emphasized feelings of isolation in their disease and discouraging health care experiences. Women in Centering noted that the biggest advantages of Centering were learning from other women with ICBPS, the creation of a welcoming and safe space, and the feeling that Centering was more of a support group than a medical visit. Women noted that barriers to Centering included cost and logistical issues, such as time and format.

Conclusions

Women with ICBPS treatment note that Centering group visits provide a sense of learning and community that opens them to a wider variety of options.
Circling the drain: the extinction crisis and the future of humanity
Authors: Dirzo Rodolfo , Ceballos Gerardo , Ehrlich Paul R.
Published: June 2022

Humanity has triggered the sixth mass extinction episode since the beginning of the Phanerozoic. The complexity of this extinction crisis is centred on the intersection of two complex adaptive systems: human culture and ecosystem functioning, although the significance of this intersection is not properly appreciated. Human beings are part of biodiversity and elements in a global ecosystem. Civilization, and perhaps even the fate of our species, is utterly dependent on that ecosystem's proper functioning, which society is increasingly degrading. The crisis seems rooted in three factors. First, relatively few people globally are aware of its existence. Second, most people who are, and even many scientists, assume incorrectly that the problem is primarily one of the disappearance of species, when it is the existential threat of myriad population extinctions. Third, while concerned scientists know there are many individual and collective steps that must be taken to slow population extinction rates, some are not willing to advocate the one fundamental, necessary, ‘simple’ cure, that is, reducing the scale of the human enterprise. We argue that compassionate shrinkage of the human population by further encouraging lower birth rates while reducing both inequity and aggregate wasteful consumption—that is, an end to growthmania—will be required.

This article is part of the theme issue ‘Ecological complexity and the biosphere: the next 30 years’.