bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Robotic Versus Laparoscopic Distal Gastrectomy for Gastric Cancer
Authors: Lu Jun , Zheng Chao-Hui , Xu Bin-Bin , Xie Jian-Wei , Wang Jia-Bin , Lin Jian-Xian , Chen Qi-Yue , Cao Long-Long , Lin Mi , Tu Ru-Hong , Huang Ze-Ning , Lin Ju-Li , Zheng Hua-Long , Huang Chang-Ming , Li Ping
Published: September 2020

Objective:

To evaluate the short-term outcomes of patients with GC who received RDG or LDG.

Summary Background Data:

Despite the increasing use of RDG in patients with GC, its safety and efficacy compared to those of LDG have not been elucidated in a randomized controlled trial.

Methods:

Three hundred patients with cT1-4a and N0/+ between September 2017 and January 2020 were enrolled in this randomized controlled trial at a high-volume hospital in China. The short-term outcomes were compared between the groups.

Results:

The modified intention-to-treat analysis included data from 283 patients (RDG group: n = 141) and (LDG group: n = 142). Patients in the RDG group exhibited faster postoperative recovery, milder inflammatory responses, and reduced postoperative morbidity (9.2% vs 17.6%, respectively, P = 0.039). Higher extraperigastric lymph nodes (LNs) were retrieved in the RDG group (17.6 ± 5.8 vs 15.8 ± 6.6, P = 0.018) with lower noncompliance rate (7.7% vs 16.9%, respectively, P = 0.006). Additionally, patients in the RDG group were more likely to initiate adjuvant chemotherapy earlier [median (interquartile range) postoperative days: 28 (24–32) vs 32 (26–42), P = 0.003]. Although total hospital costs were higher in the robotic group than in the laparoscopic group, the direct cost was lower for RDG than for LDG (all P < 0.001).

Conclusions:

RDG is associated with a lower morbidity rate, faster recovery, milder inflammatory responses, and improved lymphadenectomy. Additionally, faster postoperative recovery in the RDG group enables early initiation of adjuvant chemotherapy. Our results provide evidence for the application of RDG in patients with GC.
Compromised AMPK-PGCIα Axis Exacerbated Steatotic Graft Injury by Dysregulating Mitochondrial Homeostasis in Living Donor Liver Transplantation
Authors: Liu Jiang , Pang Li , Ng Kevin T.P. , Chiu T.L. Shirley , Liu Hui , Liu Xiaobing , Xu Aimin , Lo Chung-Mau , Man Kwan
Published: September 2020

Objective:

To investigate the association of graft steatosis with long-term outcome, and to elucidate the mechanism of steatotic graft injury in adult living donor liver transplantation.

Summary of Background Data:

The utilization of steatotic graft expands the donor pool for living donor liver transplantation (LDLT). However, it remains controversial due to its high morbidity and mortality. Elucidating the mechanism of steatotic graft injury is crucial to develop therapeutic strategies targeting at graft injury and to further expand the donor pool.

Methods:

Five hundred thirty patients receiving LDLT were prospectively included for risk factor analysis and outcome comparison. Rat orthotopic liver transplantation, in vitro functional experiments and mouse hepatic ischemia/ reperfusion models were established to explore the mechanisms of steatotic graft injury.

Results:

We identified that graft with >10% steatosis was an independent risk factor for long-term graft loss after LDLT (hazard ratio 2.652, P = 0.001), and was associated with shorter cancer recurrence-free survival and acute phase liver injury. Steatotic graft displayed distinct mitochondrial dysfunction, including membrane, calcium, and energy homeostasis dysregulation. Specifically, the mitochondrial biogenesis was remarkably downregulated in steatotic graft. Inhibition of AMPK-PGC1α axis impaired mitochondrial biogenesis and was lethal to fatty hepatocyte in vitro, whereas reactivation of AMPK promoted PGC1α-mediated mitochondrial biogenesis and attenuated liver injury via restoring mitochondrial function in animal model. Conclusions: We provided a new mechanism that compromised AMPK-PGC1α axis exacerbated steatotic graft injury in LDLT by dysregulating mitochondrial homeostasis through impairment of biogenesis.
Comparison of 3 Minimally Invasive Methods Versus Open Distal Pancreatectomy: A Systematic Review and Network Meta-Analysis
Authors: Lyu Yunxiao , Cheng Yunxiao , Wang Bin , Zhao SiCong , Chen Liang
Published: September 2020

Background:

The efficacy and safety of open distal pancreatectomy (DP), laparoscopic DP, robot-assisted laparoscopic DP, and robotic DP have not been established. The authors aimed to comprehensively compare these 4 surgical methods using a network meta-analysis.

Materials and Methods:

The authors systematically searched MEDLINE, Scopus, Web of Science, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for studies that evaluated at least 2 of the following pancreatectomy techniques: robot-assisted DP, laparoscopic DP, open DP, and robotic DP. The surface under the cumulative ranking curve (SUCRA) was applied to show the probability that each method would be the best for each outcome.

Results:

Altogether, 46 trials with 8377 patients were included in this network meta-analysis. Robotic DP showed the highest probability of having the least estimated blood loss (SUCRA, 90.9%), the lowest incidences of postoperative pancreatic fistula (SUCRA, 94.5%), clinically related postoperative pancreatic fistula (SUCRA, 94.6%), postoperative bleeding (SUCRA, 75.3%), reoperation (SUCRA, 96.4%), overall complications (SUCRA, 86.9%), and major complications (SUCRA, 99.3%), and the lowest mortality (SUCRA, 83.4%). Robotic DP also proved to be the best approach regarding the attainment of R0 resection (SUCRA, 75.4%) and the number of lymph nodes harvested (SUCRA, 64.1%).

Conclusion:

Robotic DP seems to offer clinical and oncological advantages compared with other DP methods for addressing diseases of the pancreatic body and tail, although it may require a longer operation time and learning curve. The present results require confirmation in future head-to-head randomized controlled trials.
Long-term Outcomes of Laparoscopic Heller’s Cardiomyotomy in Achalasia Cardia With Megaesophagus
Authors: Bale Manjunath , Modi Ankush , Parshad Rajinder , Suhani Suhani , Makharia Govind , Sharma Raju
Published: September 2020

Background:

Megaesophagus secondary to achalasia cardia is conventionally treated with esophagectomy. With the advent of minimal invasive surgery, laparoscopic Heller’s cardiomyotomy (LHCM) has been used in the management of megaesophagus. The authors hereby report our long-term results of 19 patients of megaesophagus managed with LHCM.

Materials and Methods:

Prospectively collected data of 19 patients with megaesophagus were reviewed for symptomatic outcome using defined symptom scores and achalasia disease-specific quality of life (A-DsQol) after LHCM with an antireflux procedure. Follow-up was done with clinical visits and telephonic calls.

Results:

The mean age of the patients was 39.8 years with 7 female and 12 male individuals. The mean duration of symptoms was 105 months. Dysphagia was the predominant symptom followed by regurgitation and heartburn. A-DsQOL was poor with a mean of 58.6±8.11. Nine patients had extra respiratory symptoms. All patients underwent LHCM with an antireflux procedure with no conversion, intraoperative perforation, or mortality. At a median follow-up of 66 months (interquartile range, 24.5 to 80), there was a significant improvement of dysphagia, regurgitation, heartburn, and Eckardt scores from 2.26±1.14, 2.05±0.62, 1.0±0.67, and 7.21±2.22 to 0.21±0.53, 0.15±0.37, 0.42±0.61, and 0.57±2.06, respectively (P<0.001). One patient (5.2%) had a recurrence of dysphagia. Sixty-three percent of patients graded their satisfaction level as fully satisfied and 31% as better. A-DsQOL of life improved significantly (P<0.001) after surgery. The respiratory symptoms improved in all.

Conclusions:

LHCM provides durable relief of symptoms in patients with megaesophagus and may be considered as the first-line treatment option in such patients.
Surgical Outcome of Laparoscopic Cholecystectomy in Patients With a History of Gastrectomy
Authors: Harino Takashi , Tomimaru Yoshito , Yokota Yuki , Noguchi Kozo , Shimizu Junzo , Taguchi Tsukasa , Yanagimoto Yoshitomo , Suzuki Yozo , Hirota Masashi , Tanida Tsukasa , Noura Shingo , Imamura Hiroshi , Iwazawa Takashi , Dono Keizo
Published: September 2020

Background:

Although laparoscopic cholecystectomy (LC) has been applied to patients with a history of abdominal surgery, we lack data on the surgical outcome of LC in patients with a history of gastrectomy. Here, we assessed the outcomes of LC and investigated predictive factors for conversion from laparoscopic to open surgery in patients with a gastrectomy history.

Patients and Methods:

We retrospectively compared the surgical outcomes of LC between patients with and without a history of gastrectomy. We performed multivariate regressions to identify independent predictive factors for open conversion during an LC.

Results:

Among 2235 patients who underwent LCs, 39 (1.7%) had undergone a previous gastrectomy (29 men, 10 women; mean age, 72 y; 34 with distal gastrectomy and 5 with total gastrectomy). The operation time, intraoperative bleeding, postoperative hospital stays, and conversion rate were significantly worse in patients with, compared with those without the history of gastrectomy. Conversion during an LC in the cases with a history of gastrectomy was significantly correlated with age and the type of gastrectomy.

Conclusions:

These results suggested that LC in patients with a history of gastrectomy exhibited worse outcomes in terms of operation time, intraoperative bleeding, postoperative hospital stay, and conversion rate than those without it. Furthermore, it was also implied that age and the type of gastrectomy were significant predictive factors for conversion during an LC in patients with a history of gastrectomy.
Objectively Confirmed Gastroesophageal Reflux Disease Following Per Oral Endoscopic Myotomy Higher in Obese Patients (BMI>30)
Authors: Ward Marc A. , Whitfield Edward P. , Hasan Salman S. , Ogola Gerald O. , Leeds Steven G.
Published: September 2020

Introduction:

Per oral endoscopic myotomy (POEM) is a promising minimally invasive therapy in the treatment of achalasia and other esophageal motility disorders. A concern surrounding POEM is the development of gastroesophageal reflux disease (GERD) postoperatively. This study was designed to report outcomes and identify risk factors for the development of postoperative GERD.

Methods:

Patients who underwent POEM between January 1, 2015 and December 12, 2019 were prospectively followed in an Institutional Review Board approved database. All patients were invited for a full comprehensive workup 6 months post-POEM including symptom scores, pH testing, manometry and esophagogastroduodenoscopy. In a retrospective review of this database, those who developed postoperative GERD were compared with those who did not.

Results:

There were 82 patients that met study criteria (median age 59). Indications for POEM include 35 type I achalasia, 16 type II achalasia, 21 type III achalasia and other spastic esophageal motility disorders, and 10 esophagogastric junction outflow obstruction. Mean Eckardt scores post-POEM were 2.67 compared with 6.79 pre-POEM (P<0.05). Mean integrated relaxation pressure improvement decreased from 27 to 13.1 (P<0.05). The presence of postoperative GERD was defined as an abnormal DeMeester score (>14.7) with pH testing off-medications or the presence of Grade C/D esophagitis on endoscopy. Thirty-five percent (29/82) of patients developed postoperative GERD following POEM. Negative predictive factors for the development of postoperative GERD include myotomy length and normal body mass index (BMI). Obesity (BMI>30) was a positive predictive risk factor in the development of GERD (P=0.029).

Conclusions:

POEM provides symptomatic relief and reduced Eckardt scores in patient with achalasia and other esophageal motility disorders. Patients who undergo POEM are at risk for developing gastroesophageal reflux disease especially in obese patients.
Comparison of Postoperative Acute Kidney Injury Between Laparoscopic and Laparotomy Procedures in Elderly Patients Undergoing Colorectal Surgery
Authors: Huang Shun , Li Zheng , Zou Nan , Dai Ting , Cao Xiang Long , Jia Zhe , Peng Wen Ping , Yang Ning , Jia Rui Fang , Zuo Ming Zhang
Published: September 2020

Objectives:

Postoperative acute kidney injury (AKI) has an unfavorable impact on both short-term and long-term outcomes. The aim of this retrospective study was to compare the incidence of postoperative AKI between laparoscopic and laparotomy procedures in elderly patients undergoing colorectal surgery.

Methods:

Medical records of elderly (65 y and older) patients who underwent colorectal cancer surgery between May 2016 and July 2018 at our tertiary hospital were reviewed. Patients with Union Internationale Contre le Cancer (UICC) stage II and III colorectal cancer, without neoadjuvant treatment, were divided into laparoscopic procedure group and laparotomy group. AKI, determined by the Acute Kidney Injury Network criteria, was compared between the 2 groups, before and after propensity matching. Multivariable analysis was made to identify independent risk factors of AKI.

Results:

In all, 285 patients met the study inclusion criteria. Postoperative AKI occurred only in 16 patients from the laparotomy group (n=212). The incidence of AKI was significantly lower in the laparoscopic procedure group (n=73) compared with the laparotomy group (0% vs. 7.5%; P=0.015). Seventy-three patients who underwent laparoscopic surgery were matched with 73 of 212 patients who underwent open surgery, by using propensity score analysis, and the incidence of AKI in the 2 groups was similar (0% vs. 8.3%; P=0.028). Multivariable analysis showed that intraoperative metaraminol dose >1 mg (odds ratio=2.742, P=0.042) is an independent risk factor for postoperative AKI.

Conclusion:

In elderly patients, the incidence of AKI after colorectal cancer surgery is lower in the laparoscopic procedure group, maybe related to hemodynamic stability and less vasoconstriction.
Decline in Club Cell Secretory Proteins, Exosomes Induction and Immune Responses to Lung Self-antigens, Kα1 Tubulin and Collagen V, Leading to Chronic Rejection After Human Lung Transplantation
Authors: Itabashi Yoshihiro , Ravichandran Ranjithkumar , Bansal Sandhya , Bharat Ankit , Hachem Ramsey , Bremner Ross , Smith Michael , Mohanakumar T.
Published: September 2020

Background.

Chronic lung allograft dysfunction (CLAD), is a major hurdle for long-term lung allograft survival after lung transplant and roughly 50% of lung transplant recipients (LTxRs) develop CLAD within 5 years. The mechanisms of CLAD development remain unknown. Donor-specific immune responses to HLA and lung self-antigens (SAgs) are vital to the pathogenesis of CLAD. Reduction in Club cell secretory protein (CCSP) has been reported in bronchoalveolar lavage (BAL) fluid samples from LTxRs with bronchiolitis obliterans syndrome (BOS). CCSP levels in BAL fluid and development of antibodies to lung SAgs in plasma were determined by ELISA. Cytokines in BAL fluid were analyzed by 30-plex Luminex panel. Exosomes from BAL fluid or plasma were analyzed for SAgs, natural killer (NK) cells markers, and cytotoxic molecules.

Results.

We demonstrate that LTxRs with BOS have lower CCSP levels up to 9 months before BOS diagnosis. LTxRs with antibodies to SAgs 1-year posttransplant also developed DSA (43%) and had lower CCSP. BOS with lower CCSP also induced Interleukin-8 and reduced vascular endothelial growth factor. Exosomes from BOS contained increased SAgs, NK cells markers, and cytotoxic molecules.

Conclusions.

We conclude lower CCSP leads to inflammation, pro-inflammatory cytokine production, immune responses to HLA and SAgs, and induction of exosomes. For the first time, we demonstrate that CCSP loss results in exosome release from NK cells capable of stimulating innate and adaptive immunity posttransplant. This increases the risk of BOS, suggesting a role of NK cell exosomes in CLAD development.
Early Versus Late Hepatocellular Carcinoma Recurrence After Transplantation: Predictive Factors, Patterns, and Long-term Outcome
Authors: El-domiaty Nada , Saliba Faouzi , Vibert Eric , Karam Vincent , Sobesky Rodolphe , Ibrahim Wafaa , Pittau Gabriella , Ciacio Oriana , Salloum Chady , Amer Khaled , Saeed Maysaa A. , Shawky Jihan A. , Sa Cunha Antonio , Rosmorduc Olivier , Cherqui Daniel , Adam René , Samuel Didier
Published: September 2020

Background.

Hepatocellular carcinoma (HCC) is currently the first indication of liver transplantation (LT) in Europe and Asia-Pacific region and the third in the United States. HCC recurrence is the main complication affecting short- and medium-term outcomes after LT.

Methods.

A total of 433 consecutive adult recipients transplanted for HCC between 2000 and 2017 (mean age: 57.8 ± 8.5 y; 83.8% were males) with a mean follow-up of 74.6 ± 58.6 months were included. Patients had to meet Milan criteria and, since 2014, alpha-fetoprotein score to be listed. Patients with HCC recurrence were classified into early (≤2 y) and late recurrence (>2 y) and were retrospectively reviewed.

Results.

Patients who developed recurrence (75 patients, 17%) had more tumors outside Milan and University of California San Francisco criteria, high alpha-fetoprotein score, and microvascular invasion at pathology. Early recurrence developed in 46 patients (61.3%); the overall 5- and 10-year survival rates of these patients from time of LT were 6.7% and 0%, which were significantly lower than those with late recurrence 64.0% and 27.1%, respectively (P < 0.001). The median survival times from the diagnosis of HCC recurrence were 15 and 17 months, respectively, in the 2 groups (P < 0.001). Multivariable Cox regression analysis identified alcoholic cirrhosis as etiology of the underlying liver disease (hazard ratio [HR] = 3.074; P = 0.007), bilobar tumor at time of LT (HR = 2.001; P = 0.037), and a tumor size (>50 mm) in the explant (HR = 1.277; P = 0.045) as independent predictors of early recurrence.

Conclusions.

Improving the prediction of early HCC recurrence could optimize patient selection for LT, potential adjuvant therapy with new targeted drugs and hence, improve long-term survival.
Inhibition of Carnitine Palmitoyltransferase 1A Aggravates Fatty Liver Graft Injury via Promoting Mitochondrial Permeability Transition
Authors: Xue Yan , Liu Hui , Yang Xin-Xiang , Pang Li , Liu Jiang , Ng Kevin T.P. , Yeung Oscar W.H. , Lam Yin-Fan , Zhang Wei-Yi , Lo Chung-Mau , Man Kwan
Published: September 2020

Background.

Hepatic steatosis is a major risk factor for graft failure due to increased susceptibility of fatty liver to ischemia-reperfusion injury (IRI) during transplantation. Here, we aimed to investigate the role of carnitine palmitoyltransferase 1A (CPT1A) in fatty liver graft injury and to explore the underlying mechanism and therapeutic potential on attenuating hepatic IRI.

Methods.

Intragraft CPT1A expression profile and the association with fatty graft injury were investigated in human and rat liver transplantation samples. The underlying mechanism and therapeutic potential of CPT1A activator against IRI were also explored in mouse hepatic ischemia-reperfusion plus major hepatectomy model and in in vitro.

Results.

CPT1A expression was significantly reduced (P= 0.0019; n = 96) in human fatty liver graft compared with normal one at early phase after transplantation. Low expression of CPT1A was significantly associated with high serum alanine aminotransferase (P= 0.0144) and aspartate aminotransferase (P= 0.0060) levels. The inhibited CPT1A and poor liver function were consistently observed in rat and mouse models with fatty livers. Furthermore, inhibition of CPT1A significantly promoted the translocation of chloride intracellular channel 1 to form chloride ion channel. The dysregulation of chloride ion channel activity subsequently triggered mitochondrial permeability transition (MPT) pore opening, exacerbated cellular oxidative stress, and energy depletion. Importantly, our intravital confocal imaging showed that CPT1A activation attenuated hepatic injury through preventing MPT after reperfusion in fatty mice.

Conclusions.

CPT1A inhibition triggered MPT contributed to severe IRI in fatty liver graft. CPT1A restoration may offer therapeutic potential on attenuating hepatic IRI.
Diagnostic Accuracy of Donor-derived Cell-free DNA in Renal-allograft Rejection: A Meta-analysis
Authors: Xiao Hanyu , Gao Fang , Pang Qidan , Xia Qiuxiang , Zeng Xianpeng , Peng Jingtao , Fan Lei , Liu Jiali , Wang Zhendi , Li Heng
Published: September 2020

Background.

Donor-derived cell-free DNA (dd-cfDNA) is a potential noninvasive molecular marker of graft rejection after kidney transplant, whose diagnostic accuracy remains controversial.

Methods.

We performed a systematic review and metaanalysis to evaluate the diagnostic accuracy of dd-cfDNA. Relevant literature was searched from online databases, and the data on the diagnostic accuracy of discriminating main rejection episodes (MRE) and antibody-mediated rejection (AMR) were merged, respectively.

Results.

Nine studies were included in the metaanalysis, of which 6 were focused on the diagnostic accuracy of dd-cfDNA for MRE, whose pooled sensitivity, specificity, area under the receiver operating characteristics curve, diagnostic odds ratio, overall positive likelihood ratio, and negative likelihood ratio with 95% confidence intervals were 0.70 (0.57-0.81), 0.78 (0.70-0.84), 0.81 (0.77-0.84), 8.18 (5.11-13.09), 3.15 (2.47-4.02), and 0.39 (0.27-0.55), respectively. Five tests were focused on discriminating AMR, whose pooled indicators were 0.84 (0.75-0.90), 0.80 (0.74-0.84), 0.89 (0.86-0.91), 20.48 (10.76-38.99), 4.13(3.21-5.33), and 0.20(0.12-0.33), respectively.

Conclusions.

Donor-derived cell-free DNA can be a helpful marker for the diagnosis of AMR among those recipients suspected of renal dysfunction. Its diagnostic accuracy on the MRE remains uncertain, which requires further prospective, large-scale, multicenter, and common population research.
Considerations for Child Cancer Survivors and Immunocompromised Children to Prevent Secondary HPV-associated Cancers
Authors: Imburgia Teresa M. , Shew Marcia L. , Gravitt Patti E. , Katzenellenbogen Rachel A.
Published: September 2020

Survivors of childhood cancer and other immunocompromised children are at high risk for the development of secondary human papillomavirus (HPV)–associated cancers. In this overview, the authors examine the epidemiology of vaccine efficacy, the natural history of HPV infections, and accelerated HPV-associated cancer development in these populations. The authors highlight the opportunities for preventive care and future research directives.
Loss to Follow-up in Adolescent and Young Adult Renal Transplant Recipients
Authors: Melanson Taylor A. , Mersha Karie , Patzer Rachel E. , George Roshan P.
Published: September 2020

Background.

Patients’ loss to follow-up (LFU) has significant impacts on outcomes and is a barrier to improving care, especially in adolescent and young adult (AYA) renal transplant recipients. There is limited information regarding the relationship between transfer of care from pediatric to adult transplant centers, age, and LFU among AYA renal transplant recipients.

Methods.

We studied 16 386 individuals aged 10–29 years who received kidney transplants between January 1, 2005 and December 31, 2015 using the Scientific Registry of Transplant Recipients. The primary outcome was LFU, which was defined as >1 year without follow-up in a transplant clinic/program. Death or graft failure within a year of the last follow-up was not classified as LFU. We performed a retrospective cohort study describing LFU using Pearson’s chi-square tests. Multivariable logistic regression was used to estimate the change in likelihood of LFU associated with recipient characteristics and institution transfer.

Results.

In total, 22.26% (n = 3647) of our study population met criteria for LFU. About 11.17% (n = 1830) transferred institutions during the study period. LFU occurred in 50.18% of recipients who transferred institutions. LFU peaked at the age of 20 years, with 7.4% of 20-year-olds having LFU. The odds of LFU among renal transplant recipients who transferred institutions were 3.36 times greater (95% confidence interval, 3.1-3.6) than the odds of LFU among those who did not transfer institutions.

Conclusions.

LFU is a critical problem faced by AYA renal transplant recipients, and institution transfer is a significant risk factor for LFU. Additional studies investigating the interplay between age, institution transfer, and LFU in the AYA population are still needed.
Inhibition of Glycogen Synthase Kinase 3β Alleviates Chronic Renal Allograft Dysfunction in Rats
Authors: Deng Jin , Wang Xin , Zhou Qin , Xia Yue , Xiong Chongxiang , Shao Xiaofei , Zou Hequn
Published: September 2020

Background.

Chronic renal allograft dysfunction (CRAD) is a major condition that impedes the long-term survival of renal allografts. However, the mechanism of CRAD is obscure, and the effective strategies for controlling the progression of CRAD are lacking. The present study used a CRAD rat model to assess the effect of glycogen synthase kinase 3β (GSK-3β) inhibition on the development of CRAD.

Methods.

A classical F334-to-LEW orthotopic renal transplantation was performed on the CRAD group. The treatment group was treated with the GSK-3β inhibitor 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione for 12 consecutive weeks following renal transplantation. The study included uninephrectomized F344 and Lewis rats as control subjects. Twelve weeks post surgery, the rats were retrieved for analysis of renal function, urine protein levels, histological, immunohistochemical, and molecular biological parameters.

Results.

Administration of 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione inactivated GSK-3β and thereby improved renal function, attenuated proteinuria, and reduced renal tissue damage in CRAD rats. Besides, inactivation of GSK-3β inhibited nuclear factor-κB activation, macrophage infiltration, and expression of multiple proinflammatory cytokines/chemokines. Inhibition of GSK-3β also decreased the levels of malondialdehyde, increased superoxide dismutase levels, upregulated the expression of heme oxygenase-1 and NAD(P)H quinone oxidoreductase-1, and enhanced nuclear translocation of nuclear factor erythroid 2-related factor 2 in the kidneys of CRAD rats.

Conclusions.

Inhibition of GSK-3β attenuates the development of CRAD by inhibiting inflammation and oxidant stress. Thus, GSK-3β inhibition may represent a potential therapeutic strategy for the prevention and treatment of CRAD.
COVID-19 Outcomes Among Solid Organ Transplant Recipients: A Case-control Study
Authors: Sharma Pratima , Chen Vincent , Fung Christopher M. , Troost Jonathan P. , Patel Vaiibhav N. , Combs Michael , Norman Silas , Garg Puneet , Colvin Monica , Aaronson Keith , Sonnenday Christopher J. , Golob Jonathan L. , Somers Emily C. , Doshi Mona M.
Published: September 2020

Background.

Solid organ transplant (SOT) recipients are considered to be “vulnerable” to COVID-19 infection due to immunosuppression. To date, there are no studies that compared the disease severity of COVID-19 in SOT recipients with nontransplant patients.

Methods.

In this case-control study, we compared the outcomes of COVID-19 between SOT recipients and their matched nontransplant controls. The cases were all adult SOT recipients (N = 41) from our academic health center who were diagnosed with COVID-19 between March 10, 2020 and May 15, 2020 using positive reverse transcriptase polymerase chain reaction for SARS-CoV2. The controls (N = 121) were matched on age (±5 y), race, and admission status (hospital or outpatient). The primary outcome was death and secondary outcomes were severe disease, intubation and renal replacement therapy (RRT).

Results.

Median age of SOT recipients (9 heart, 3 lung, 16 kidney, 8 liver, and 5 dual organ) was 60 y, 80% were male and 67% were Black. Severe disease adjusted risk of death was similar in both the groups (hazard ratio = 0.84 [0.32–2.20]). Severity of COVID-19 and intubation were similar, but the RRT use was higher in SOT (odds ratio = 5.32 [1.26, 22.42]) compared to non-SOT COVID-19 patients. Among SOT recipients, COVID-19-related treatment with hydroxychloroquine (HCQ) was associated with 10-fold higher hazard of death compared to without HCQ (hazard ratio = 10.62 [1.24–91.09]).

Conclusions.

Although African Americans constituted one-tenth of all SOT in our center, they represented two-thirds of COVID-19 cases. Despite high RRT use in SOT recipients, the severe disease and short-term death were similar in both groups. HCQ for the treatment of COVID-19 among SOT recipients was associated with high mortality and therefore, its role as a treatment modality requires further scrutiny.
SARS-CoV-2 phylogeny during the early outbreak in the Basel area, Switzerland: import and spread dominated by a single B.1 lineage variant (C15324T)
Authors: Stange Madlen , Mari Alfredo , Roloff Tim , Seth-Smith Helena MB , Schweitzer Michael , Brunner Myrta , Leuzinger Karoline , Søgaard Kirstine K. , Gensch Alexander , Tschudin-Sutter Sarah , Fuchs Simon , Bielicki Julia , Pargger Hans , Siegemund Martin , Nickel Christian H , Bingisser Roland , Osthoff Michael , Bassetti Stefano , Schneider-Sliwa Rita , Battegay Manuel , Hirsch Hans H , Egli Adrian
Published: September 2020

Background

The first case of SARS-CoV-2 in Basel, Switzerland, was detected on February 26th2020. We present a phylogenetic longitudinal study and explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26thuntil March 23rd.

Methods

We sequenced SARS-CoV-2 from naso-oropharyngeal swabs, generated 468 high quality genomes, and called variants with our COVID-19 Pipeline (COVGAP). We analysed viral genetic diversity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny.

Findings

The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected from March 2nd, although the first lineage identified was B.1.1. Within B.1, a clade containing 68·2% of our samples, defined by the SNP C15324T, suggests local spreading events. We infer the geographic origin of this mutation to our tri-national region. The remaining genomes map broadly over the global phylogenetic tree, evidencing several events of introduction from and/or dissemination to other regions of the world. We also observe family transmission events.

Interpretation

A single lineage dominated the outbreak in the City of Basel while other lineages such as the first (B1.1) did not propagate. Thus spreading events seem to have contributed most to viral spread, while travel returners and family transmissions were better controlled by the recommended measures. This phylogenetic analysis enriches epidemiological and contact tracing data, allowing connection of seemingly unconnected events, and can inform public health interventions.

Funding

No dedicated funding was used for this work.
Personalized Prediction of Disease Activity in Patients with Rheumatoid Arthritis Using an Adaptive Deep Neural Network
Authors: Hügle Maria , Walker Ulrich A. , Finckh Axel , Müller Rüdiger , Kalweit Gabriel , Scherer Almut , Boedecker Joschka , Hügle Thomas
Published: September 2020

Background

Rheumatoid arthritis (RA) lacks reliable biomarkers that predict disease evolution on an individual basis, potentially leading to over- and undertreatment. Deep neural networks learn from former experiences on a large scale and can be used to predict future events as a potential tool for personalized clinical assistance.

Objective

To investigate deep learning for the prediction of individual disease activity in RA.

Methods

Demographic and disease characteristics from over 9500 patients and 65.000 visits from the Swiss Quality Management (SCQM) database were used to train and evaluate an adaptive recurrent neural network (AdaptiveNet). Patient and disease characteristics along with clinical and patient reported outcomes, laboratory values and medication were used as input features. DAS28-BSR was used to predict active disease and future numeric individual disease activity by classification and regression, respectively.

Results

AdaptiveNet predicted active disease defined as DAS28-BSR>2.6 at the next visit with an overall accuracy of 75.6% and a sensitivity and specificity of 84.2% and 61.5%, respectively. Regression allowed forecasting individual DAS28-BSR values with a mean squared error of 0.9, corresponding to a variation between predicted and true values at next visit of 8%. Apart from DAS28-BSR, the most influential characteristics to predict disease activity were joint pain, disease duration, age and duration of treatment. Longer disease duration, age >50 years or antibody positivity marginally improved prediction performance.

Conclusion

Deep neural networks have the capacity to predict individual numeric disease activity in RA. Low specificity remains challenging and might benefit from alternative input data or outcome targets.
Prospective evaluation of genome sequencing versus standard-of-care as a first molecular diagnostic test
Authors: Brockman Deanna G. , Austin-Tse Christina A. , Pelletier Renée C. , Harley Caroline , Patterson Candace , Head Holly , Leonard Courtney Elizabeth , O’Brien Kimberly , Mahanta Lisa M. , Lebo Matthew S. , Lu Christine Y. , Natarajan Pradeep , Khera Amit V. , Aragam Krishna G. , Kathiresan Sekar , Rehm Heidi L. , Udler Miriam
Published: September 2020

Purpose

To evaluate the diagnostic yield and clinical utility of clinical genome sequencing (cWGS) as a first genetic test for patients with suspected monogenic disorders.

Methods

We conducted a prospective randomized study with pediatric and adult patients recruited from genetics clinics at Massachusetts General Hospital who were undergoing planned genetic testing. Participants were randomized into two groups: standard-of-care genetic testing (SOC) only or SOC and cWGS.

Results

204 participants were enrolled and 99 received cWGS. cWGS returned 23 molecular diagnoses in 20 individuals: A diagnostic yield of 20% (20/99, 95%CI 12.3-28.1%)), which was not significantly different from SOC (17%, 95%CI 9.7%-24.6%, P=0.584). 19/23 cWGS diagnoses provided an explanation for clinical features or were considered worthy of additional workup by referring providers. While cWGS detected all variants reported by SOC, SOC failed to capture 9/23 cWGS diagnoses; primarily due to genes not included in SOC tests. Turnaround time was significantly shorter for SOC compared to cWGS (33.9 days vs 87.2 days, P<0.05).

Conclusions

cWGS is technically suitable as a first genetic test and identified clinically relevant variants not captured by SOC. However, further studies addressing other variant types and implementation challenges are needed to support feasibility of its broad-scale adoption.
SARS-CoV-2-specific IgA and limited inflammatory cytokines are present in the stool of select patients with acute COVID-19
Authors: Britton Graham J. , Chen-Liaw Alice , Cossarini Francesca , Livanos Alexandra E. , Spindler Matthew P. , Plitt Tamar , Eggers Joseph , Mogno Ilaria , Gonzalez-Reiche Ana S. , Siu Sophia , Tankelevich Michael , Grinspan Lauren Tal , Dixon Rebekah E. , Jha Divya , Martinez-Delgado Gustavo , Amanat Fatima , Hoagland Daisy A. , tenOever Benjamin R. , Dubinsky Marla C. , Merad Miriam , Bakel Harm van , Krammer Florian , Bongers Gerold , Mehandru Saurabh , Faith Jeremiah J.
Published: September 2020

Background and aims

Immune dysregulation caused by SARS-CoV-2 infection is thought to play a pathogenic role in COVID-19. SARS-CoV-2 can infect a variety of host cells, including intestinal epithelial cells. We sought to characterize the role of the gastrointestinal immune system in the pathogenesis of the inflammatory response associated with COVID-19.

Methods

We measured cytokines, inflammatory markers, viral RNA, microbiome composition and antibody responses in stool and serum samples from a prospectively enrolled cohort of 44 hospitalized COVID-19 patients.

Results

SARS-CoV-2 RNA was detected in stool of 41% of patients and was found more frequently in patients with diarrhea than those without (16[44%] vs 5[19%], p=0.06). Patients who survived had lower median viral genome copies than those who did not (p=0.021). Compared to uninfected controls, COVID-19 patients had higher median fecal levels of IL-8 (166.5 vs 286.5 pg/mg; p=0.05) and lower levels of fecal IL-10 (678 vs 194 pg/mg; p<0.001) compared to uninfected controls. Stool IL-23 was higher in patients with more severe COVID-19 disease (223.8 vs 86.6 pg/mg; p=0.03) and we find evidence of intestinal virus-specific IgA responses, which was associated with more severe disease. Fecal cytokines and calprotectin levels were not correlated with gastrointestinal symptoms or with the level of virus detected.

Conclusions

Although SARS-CoV-2 RNA was detectable in the stools of COVID-19 patients and select individuals had evidence for a specific mucosal IgA response, intestinal inflammation was limited, even in patients presenting with gastrointestinal symptoms.
Computational Modeling Identifies Embolic Stroke of Undetermined Source Patients with Potential Arrhythmic Substrate
Authors: Bifulco Savannah F. , Scott Griffin D. , Sarairah Sakher , Birjandian Zeinab , Roney Caroline H. , Niederer Steven A. , Mahnkopf Christian , Kuhnlein Peter , Mitlacher Marcel , Tirschwell David , Longstreth W. T. , Akoum Nazem , Boyle Patrick M.
Published: September 2020

Cardiac magnetic resonance imaging (MRI) has revealed fibrosis in embolic stroke of undetermined source (ESUS) patients comparable to levels seen in atrial fibrillation (AFib). We used computational modeling to understand the absence of arrhythmia in ESUS despite the presence of putatively pro-arrhythmic fibrosis. MRI-based atrial models were reconstructed for 45 ESUS and 45 AFib patients. The fibrotic substrate’s arrhythmogenic capacity in each patient was assessed computationally. Reentrant drivers were induced in 24/45 (53%) ESUS and 22/45 (49%) AFib models. Inducible models had more fibrosis (16.7±5.45%) than non-inducible models (11.07±3.61%; P<0.0001); however, inducible subsets of ESUS and AFib models had similar fibrosis levels (P=0.90), meaning theintrinsic pro-arrhythmic substrate propertiesof fibrosis in ESUS and AFib are indistinguishable. This suggests some ESUS patients have latent pre-clinical fibrotic substrate that could be a future source of arrhythmogenicity. Thus, our work prompts the hypothesis that ESUS patients with fibrotic atria are spared from AFib due to an absence of arrhythmia triggers.
Nutritional efficacy of Chlorella supplementation depends on the individual gut environment: randomized control study
Authors: Nishimoto Yuichiro , Nomaguchi Tatsuhiro , Mori Yuka , Ito Masaki , Nakamura Yuya , Fujishima Masaki , Murakami Shinnosuke , Yamada Takuji , Fukuda Shinji
Published: September 2020

Recent studies have accumulated evidence that the intestinal environment is strongly correlated with host diet, which influences host health. A number of dietary products whose mechanisms of influence operate via the gut microbiota have been revealed, but they are still limited. Here, we investigated the dietary influence of Chlorella, a green alga commercially available as a dietary supplement. A randomized, double-blind, placebo-controlled crossover trial including 40 Japanese participants with constipation was performed and followed by integrated analysis of the gut microbiome, gut metabolome and blood parameters based on a metabologenomics approach. We revealed that the consumption of Chlorella increased the level of several dicarboxylic acids in faeces. Furthermore, the analysis showed that individuals with low concentrations of faecal propionate increased its concentration by Chlorella intake. In addition, increasing of blood folate levels were negatively correlated with defecation frequency at baseline. Our study suggested that the effect of Chlorella consumption varies by individuals depending on their intestinal environment, which illustrates the importance of stratified dietary management based on the intestinal environment in individuals.
Perception of game-based rehabilitation in upper-limb prosthetic training: a survey of users and researchers
Authors: Garske Christian , Dyson Matthew , Dupan Sigrid , Nazarpour Kianoush
Published: September 2020

Background

Serious games have been investigated for their use in multiple forms of rehabilitation for decades. The rising trend to use games for physical fitness in more recent years has also provided more options and garnered more interest for their use in physical rehabilitation and motor learning. In this paper, we report the results of an opinion survey of serious games in upper limb prosthetic training.

Objective

This study investigates and contrasts the expectations and preferences for game based prosthetic rehabilitation of people with limb difference and researchers.

Methods

Both participant groups answered open and closed questions as well as a questionnaire to assess their user types. The distribution of the user types was compared with a Pearson’s χ2 test against a sample population. The data was analysed with the thematic framework method; answers fell within the themes of usability, training, and game design. Researchers shared their views on current challenges and what could be done to tackle these.

Results

A total of 14 people with limb difference and 12 researchers took part in this survey. The open questions resulted in an overview of the different views on prosthetic training games between the groups. The user types of people with limb difference and researchers were both significantly different from the sample population with χ2=12.31 and χ2=26.50, respectively.

Conclusions

We found that the respondents show a general willingness and tentative optimism towards the topic, but also acknowledge hurdles limiting the adoption of these games by both clinics and users. Results indicate a noteworthy difference between researchers and limb different people in their game preferences, which could lead to design choices that do not represent the target audience. Furthermore, focus on long-term in-home experiments is expected to shed more light onto the validity of games in upper limb prosthetic rehabilitation.
Evaluating the Influence of Mood and Stress on Glycemic Variability in T1DM Patients using Glucose Monitoring Sensors and Pools
Authors: Contador Sergio , Botella Marta , Aramendi Aranzazu , Martínez Remedios , Maqueda Esther , Garnica Oscar , Velasco J. Manuel , Lanchares Juan , Hidalgo J. Ignacio
Published: September 2020

Objective

Assess in a sample of patients with type 1 diabetes mellitus whether mood and stress influence blood glucose levels and variability.

Material and Methods

Continuous glucose monitoring was performed on 10 patients with type 1 diabetes, where interstitial glucose values were recorded every 15 minutes. A daily survey was conducted through Google Forms, collecting information on mood and stress. The day was divided into 6 slots of 4-hour each, asking the patient to assess each slot in relation to mood (sad, normal or happy) and stress (calm, normal or nervous). Different measures of glycemic control (arithmetic mean and percentage of time below/above the target range) and variability (standard deviation, percentage coefficient of variation, mean amplitude of glycemic excursions and mean of daily differences) were calculated to relate the mood and stress perceived by patients with blood glucose levels and glycemic variability. A hypothesis test was carried out to quantitatively compare the data groups of the different measures using the Student’s t-test.

Results

Statistically significant differences (p-value < 0.05) were found between different levels of stress. In general, average glucose and variability decrease when the patient is calm. There are statistically significant differences (p-value < 0.05) between different levels of mood. Variability increases when the mood changes from sad to happy. However, the patient’s average glucose decreases as the mood improves.

Conclusions

Variations in mood and stress significantly influence blood glucose levels, and glycemic variability in the patients analyzed with type 1 diabetes mellitus. Therefore, they are factors to consider for improving glycemic control. The mean of daily differences does not seem to be a good indicator for variability.
Adjusted Dynamics of COVID-19 Pandemic due to Herd Immunity in Bangladesh
Authors: Hoque Md. Enamul , Islam Md. Shariful , Amin Mohammad Ruhul , Das Susanta Kumar , Mitra Dipak Kumar
Published: September 2020

Amid growing debate between scientists and policymakers on the trade-off between public safety and reviving economy during the COVID-19 pandemic, the government of Bangladesh decided to relax the countrywide lockdown restrictions from the beginning of June 2020. Instead, the Ministry of Public Affairs officials have declared some parts of the capital city and a few other districts as red zones or high-risk areas based on the number of people infected in the late June 2020. Nonetheless, the COVID-19 infection rate had been increasing in almost every other part of the country. Ironically, rather than ensuring rapid tests and isolation of COVID-19 patients, from the beginning of July 2020, the Directorate General of Health Services restrained the maximum number of tests per laboratory. Thus, the health experts have raised the question of whether the government is heading toward achieving herd immunity instead of containing the COVID-19 pandemic. In this article, the dynamics of the pandemic due to SARS-CoV-2 in Bangladesh are analyzed with the SIRD model. We demonstrate that the herd immunity threshold can be reduced to 31% than that of 60% by considering age group cluster analysis resulting in a total of 53.0 million susceptible populations. With the data of Covid-19 cases till July 22, 2020, the time-varying reproduction numbers are used to explain the nature of the pandemic. Based on the estimations of active, severe, and critical cases, we discuss a set of policy recommendations to improve the current pandemic control methods in Bangladesh.
College campuses and COVID-19 mitigation: clinical and economic value
Authors: Losina Elena , Leifer Valia , Millham Lucia , Panella Christopher , Hyle Emily P. , Mohareb Amir M. , Neilan Anne M. , Ciaranello Andrea L. , Kazemian Pooyan , Freedberg Kenneth A.
Published: September 2020

Background

Decisions around US college and university operations will affect millions of students and faculty amidst the COVID-19 pandemic. We examined the clinical and economic value of different COVID-19 mitigation strategies on college campuses.

Methods

We used the Clinical and Economic Analysis of COVID-19 interventions (CEACOV) model, a dynamic microsimulation that tracks infections accrued by students and faculty, accounting for community transmissions. Outcomes include infections, $/infection-prevented, and $/quality-adjusted-life-year ($/QALY). Strategies included extensive social distancing (ESD), masks, and routine laboratory tests (RLT). We report results per 5,000 students (1,000 faculty) over one semester (105 days).

Results

Mitigation strategies reduced COVID-19 cases among students (faculty) from 3,746 (164) with no mitigation to 493 (28) with ESD and masks, and further to 151 (25) adding RLTq3 among asymptomatic students and faculty. ESD with masks cost $168/infection-prevented ($49,200/QALY) compared to masks alone. Adding RLTq3 ($10/test) cost $8,300/infection-prevented ($2,804,600/QALY). If tests cost $1, RLTq3 led to a favorable cost of $275/infection-prevented ($52,200/QALY). No strategies without masks were cost-effective.

Conclusion

Extensive social distancing with mandatory mask-wearing could prevent 87% of COVID-19 cases on college campuses and be very cost-effective. Routine laboratory testing would prevent 96% of infections and require low cost tests to be economically attractive.