bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of lenvatinib monotreatment and lenvatinib-based combination therapy for patients with unresectable hepatocellular carcinoma: a retrospective, real-world study in China
Authors: Zhu Yun , Sun Penghui , Wang Kunyuan , Xiao Shuzhe , Cheng Yanling , Li Xiangzhao , Wang Biao , Li Jiancong , Yu Wenxuan , Cheng Yang
Published: September 2021

Background

Lenvatinib and lenvatinib-based combination treatments are widely used in patients with unresectable hepatocellular carcinoma (uHCC) in clinical practice, but their curative effect and safety need further study in the real world.

Methods

This was a retrospective study involving patients with uHCC receiving lenvatinib monotherapy and lenvatinib-based combination treatment between Nov, 2018 and Sep, 2020 in Nanfang Hospital. Efficacy was evaluated with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), time to tumor progression (TTP), and overall survival (OS). Treatment-related adverse events (TRAEs) were recorded and graded. Efficacy and safety of monotherapy and combination therapy were compared. Stratified analysis was performed according to systemic line of treatment and medication regimen for combination therapy.

Results

For lenvatinib monotherapy (n = 39), OS and PFS were 80 weeks and 24.3 weeks, respectively. For combination treatment (n = 72), median OS and PFS were 99 weeks and 45.6 weeks, respectively. OS, PFS, and TTP for patients in the combination treatment cohort were significantly longer compared to those of patients in the monotreatment cohort (OS: P = 0.04, PFS: P = 0.003; TTP, P = 0.005). The incidence of TRAEs could be controlled both in the monotherapy cohort and the combination treatment cohort. In the monotherapy cohort, OS and PFS were significantly decreased in the second-line treatment group compared with the first-line treatment group, while no differences were observed in the combination cohort. The efficacy of triple therapy (lenvatinib plus PD-1 antibody plus TACE or HAIF) was similar to lenvatinib plus PD-1 antibody or lenvatinib plus TACE or HAIF.

Conclusions

Our real-world study showed that lenvatinib monotherapy and lenvatinib-based combination therapy were well tolerated, with encouraging efficacies in patients with uHCC. Lenvatinib-based combination therapy showed a better curative effect compared with lenvatinib single-agent therapy. In patients who have failed first-line TKI treatment, lenvatinib-based combination therapy may be a better choice than lenvatinib single-agent therapy. Lenvatinib-based triple therapy may not have an advantage over dual therapy.
Climate change, extreme events, and increased risk of salmonellosis: foodborne diseases active surveillance network (FoodNet), 2004-2014
Authors: Morgado Michele E. , Jiang Chengsheng , Zambrana Jordan , Upperman Crystal Romeo , Mitchell Clifford , Boyle Michelle , Sapkota Amy R. , Sapkota Amir
Published: September 2021

Background

Infections with nontyphoidal Salmonella cause an estimated 19,336 hospitalizations each year in the United States. Sources of infection can vary by state and include animal and plant-based foods, as well as environmental reservoirs. Several studies have recognized the importance of increased ambient temperature and precipitation in the spread and persistence of Salmonella in soil and food. However, the impact of extreme weather events on Salmonella infection rates among the most prevalent serovars, has not been fully evaluated across distinct U.S. regions.

Methods

To address this knowledge gap, we obtained Salmonella case data for S. Enteriditis, S. Typhimurium, S. Newport, and S. Javiana (2004-2014; n = 32,951) from the Foodborne Diseases Active Surveillance Network (FoodNet), and weather data from the National Climatic Data Center (1960-2014). Extreme heat and precipitation events for the study period (2004-2014) were identified using location and calendar day specific 95th percentile thresholds derived using a 30-year baseline (1960-1989). Negative binomial generalized estimating equations were used to evaluate the association between exposure to extreme events and salmonellosis rates.

Results

We observed that extreme heat exposure was associated with increased rates of infection with S. Newport in Maryland (Incidence Rate Ratio (IRR): 1.07, 95% Confidence Interval (CI): 1.01, 1.14), and Tennessee (IRR: 1.06, 95% CI: 1.04, 1.09), both FoodNet sites with high densities of animal feeding operations (e.g., broiler chickens and cattle). Extreme precipitation events were also associated with increased rates of S. Javiana infections, by 22% in Connecticut (IRR: 1.22, 95% CI: 1.10, 1.35) and by 5% in Georgia (IRR: 1.05, 95% CI: 1.01, 1.08), respectively. In addition, there was an 11% (IRR: 1.11, 95% CI: 1.04-1.18) increased rate of S. Newport infections in Maryland associated with extreme precipitation events.

Conclusions

Overall, our study suggests a stronger association between extreme precipitation events, compared to extreme heat, and salmonellosis across multiple U.S. regions. In addition, the rates of infection with Salmonella serovars that persist in environmental or plant-based reservoirs, such as S. Javiana and S. Newport, appear to be of particular significance regarding increased heat and rainfall events.
Comparison of false-discovery rates of various decoy databases
Authors: Lee Sangjeong , Park Heejin , Kim Hyunwoo
Published: September 2021

Background

The target-decoy strategy effectively estimates the false-discovery rate (FDR) by creating a decoy database with a size identical to that of the target database. Decoy databases are created by various methods, such as, the reverse, pseudo-reverse, shuffle, pseudo-shuffle, and the de Bruijn methods. FDR is sometimes over- or under-estimated depending on which decoy database is used because the ratios of redundant peptides in the target databases are different, that is, the numbers of unique (non-redundancy) peptides in the target and decoy databases differ.

Results

We used two protein databases (the UniProt Saccharomyces cerevisiae protein database and the UniProt human protein database) to compare the FDRs of various decoy databases. When the ratio of redundant peptides in the target database is low, the FDR is not overestimated by any decoy construction method. However, if the ratio of redundant peptides in the target database is high, the FDR is overestimated when the (pseudo) shuffle decoy database is used. Additionally, human and S. cerevisiae six frame translation databases, which are large databases, also showed outcomes similar to that from the UniProt human protein database.

Conclusion

The FDR must be estimated using the correction factor proposed by Elias and Gygi or that by Kim et al. when (pseudo) shuffle decoy databases are used.
Clinical outcomes and effect on intraoperative blood loss and postoperative pain of patients undergoing retroperitoneal laparoscopic partial nephrectomy for complex renal tumors
Authors: Guo Yansong , Xu Qian , Chen Baochun , Liu Lifeng , Wang Yuanyuan , Zhu Ai , Tian Longjiang
Published: September 2021

Objective

To explore the clinical outcomes and effect on intraoperative blood loss and postoperative pain of patients undergoing the retroperitoneal laparoscopic partial nephrectomy (RLPN) for complex renal tumors.

Methods

Fifty patients with complex renal tumor admitted to our hospital from February 2017 to February 2019 were selected as the research object and divided into the RLPN group (given the retroperitoneal laparoscopic partial nephrectomy, n = 24) and the OPN group (given the open partial nephrectomy, n = 26) by number table method to compare their various perioperative indicators and serum stress response and analyze the clinical effect of different surgical methods on the complex renal tumor.

Results

The clinical information of patients in both groups were not significantly different (P > 0.05); in addition to the operative time, the intraoperative blood loss, hospital stay, warm ischemia time, and numerical rating scale (NRS) scores of the RLPN group were clearly lower than those of the OPN group (P < 0.05); after treatment, patients in the RLPN group obtained significantly lower white blood cell (WBC) count, cortisol, and c-reactive protein (CRP) levels than the OPN group (P < 0.05); the renal glomerular filtration rate (GFR) of the affected side, quality of life scores, and 3-year overall survival rate of treated patients in the RLPN group were obviously higher than those in the OPN group (P < 0.05); and patients in the RPLN group had significantly lower incidence rate (P < 0.05).

Conclusion

Compared with OPN, RLPN is more worthy of promotion and application, because it has better treatment outcomes, significantly reduces intraoperative blood loss, alleviates the body stress response and postoperative pain, and improves the quality of life.
Higher preconceptional maternal body mass index is associated with faster early preimplantation embryonic development: the Rotterdam periconception cohort
Authors: van Duijn Linette , Rousian Melek , Hoek Jeffrey , Willemsen Sten P. , van Marion Eva S. , Laven Joop S. E. , Baart Esther B. , Steegers-Theunissen Régine P. M.
Published: September 2021

Background

Overweight and obesity affect millions of people globally, which has also serious implications for reproduction. For example, treatment outcomes after in vitro fertilisation (IVF) are worse in women with a high body mass index (BMI). However, the impact of maternal BMI on embryo quality is inconclusive. Our main aim is to study associations between preconceptional maternal BMI and morphokinetic parameters of preimplantation embryos and predicted implantation potential. In addition, associations with clinical IVF outcomes are investigated.

Methods

From a tertiary hospital, 268 women undergoing IVF or IVF with intracytoplasmic sperm injection (ICSI) were included; 143 normal weight, 79 overweight and 46 obese women. The embryos of these women were cultured in the EmbryoScope, a time-lapse incubator. The morphokinetic parameters of preimplantation embryos and predicted implantation potential, assessed by the KIDScore algorithm were longitudinally evaluated as primary and secondary outcomes, respectively. The tertiary outcomes included clinical outcomes, i.e., fertilization, implantation and live birth rate.

Results

After adjustment for patient- and treatment-related factors, we demonstrated in 938 embryos that maternal BMI is negatively associated with the moment of pronuclear appearance (βtPNa-0.070 h (95%CI -0.139, -0.001),p = 0.048), pronuclear fading (βtPNf-0.091 h (95%CI -0.180, -0.003),p = 0.043 and the first cell cleavage (βt2-0.111 h (95%CI -0.205, -0.016),p = 0.022). Maternal BMI was not significantly associated with the KIDScore and tertiary clinical treatment outcomes. In embryos from couples with female or combined factor subfertility, the impact of maternal BMI was even larger (βtPNf-0.170 h (95%CI -0.293, -0.047),p = 0.007; βt2-0.199 h (95%CI -0.330, -0.067),p = 0.003). Additionally, a detrimental impact of BMI per point increase was observed on the KIDScore (β -0.073 (se 0.028),p = 0.010).

Conclusions

Higher maternal BMI is associated with faster early preimplantation development. In couples with female or combined factor subfertility, a higher BMI is associated with a lower implantation potential as predicted by the KIDScore. Likely due to power issues, we did not observe an impact on clinical treatment outcomes. However, an effect of faster preimplantation development on post-implantation development is conceivable, especially since the impact of maternal BMI on pregnancy outcomes has been widely demonstrated.
The ameliorative effect of ellagic acid on di-(2-ethylhexyl) phthalate-induced testicular structural alterations, oxidative stress, inflammation and sperm damages in adult mice
Authors: Hosseinzadeh Azam , Mehrzadi Saeed , Siahpoosh Amir , Basir Zahra , Bahrami Nosrat , Goudarzi Mehdi
Published: September 2021

Background

Phthalates such as di (2-ethylhexyl) phthalate (DEHP) are well known exogenous substances, disrupting reproductive system function and structure. The current research demonstrated the effect of ellagic acid (EA) on DEHP-induced testicular injury in mice.

Methods

Thirty-five healthy adult male mice were randomly divided to five groups; normal saline receiving group, DEHP (2 g/kg/day, dissolved in corn oil, p.o.) receiving group, DEHP (2 g/kg/day, dissolved in corn oil, p.o.) and EA receiving groups (25, 50 and 100 mg/kg/day, p.o.). Treatment duration of animals was 14 days. Body and testes weights and sperm characteristics and histological changes of testes were evaluated. Serum testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were analyzed. In the testicular tissue, oxidative/nitrosative stress markers and inflammatory cytokine levels were measured.

Results

Ellagic acid significantly reduced DEHP-induced reduction of body and testes weights. The DEHP-induced reduction of spermatogonia, primary spermatocyte and sertoli cells numbers as well as reduction of sperm vitality and progressive motility were reversed by EA. Furthermore, EA inhibited DEHP-induced alterations in serum hormone levels. These effects were associated with the reduction of DEHP-induced increased level of oxidative stress and inflammatory responses.

Conclusions

Ellagic acid considerably inhibits testicular toxicity of DEHP through reducing oxidative/nitrosative stress and inflammatory responses. Our data suggest that EA may be considered as a promising agent to inhibit male reproductive toxicity induced by endocrine disrupting chemicals such as DEHP.
The CNS-penetrant soluble guanylate cyclase stimulator CYR119 attenuates markers of inflammation in the central nervous system
Authors: Correia Susana S. , Liu Guang , Jacobson Sarah , Bernier Sylvie G. , Tobin Jenny V. , Schwartzkopf Chad D. , Atwater Emily , Lonie Elisabeth , Rivers Sam , Carvalho Andrew , Germano Peter , Tang Kim , Iyengar Rajesh R. , Currie Mark G. , Hadcock John R. , Winrow Christopher J. , Jones Juli E.
Published: September 2021

Background

Inflammation in the central nervous system (CNS) is observed in many neurological disorders. Nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO–sGC–cGMP) signaling plays an essential role in modulating neuroinflammation. CYR119 is a CNS-penetrant sGC stimulator that amplifies endogenous NO–sGC–cGMP signaling. We evaluated target engagement and the effects of CYR119 on markers of neuroinflammation in vitro in mouse microglial cells and in vivo in quinolinic acid (QA)-induced and high-fat diet-induced rodent neuroinflammation models.

Methods

Target engagement was verified in human embryonic kidney (HEK) cells, rat primary neurons, mouse SIM-A9 cells, and in rats by measuring changes in cGMP and downstream targets of sGC signaling [phosphorylated vasodilator-stimulated phosphoprotein (pVASP), phosphorylated cAMP-response element binding (pCREB)]. In SIM-A9 cells stimulated with lipopolysaccharides (LPS), markers of inflammation were measured when cells were treated with or without CYR119. In rats, microinjections of QA and vehicle were administered into the right and left hemispheres of striatum, respectively, and then rats were dosed daily with either CYR119 (10 mg/kg) or vehicle for 7 days. The activation of microglia [ionized calcium binding adaptor molecule 1 (Iba1)] and astrocytes [glial fibrillary acidic protein (GFAP)] was measured by immunohistochemistry. Diet-induced obese (DIO) mice were treated daily with CYR119 (10 mg/kg) for 6 weeks, after which inflammatory genetic markers were analyzed in the prefrontal cortex.

Results

In vitro, CYR119 synergized with exogenous NO to increase the production of cGMP in HEK cells and in primary rat neuronal cell cultures. In primary neurons, CYR119 stimulated sGC, resulting in accumulation of cGMP and phosphorylation of CREB, likely through the activation of protein kinase G (PKG). CYR119 attenuated LPS-induced elevation of interleukin 6 (IL-6) and tumor necrosis factor (TNF) in mouse microglial cells. Following oral dosing in rats, CYR119 crossed the blood–brain barrier (BBB) and stimulated an increase in cGMP levels in the cerebral spinal fluid (CSF). In addition, levels of proinflammatory markers associated with QA administration or high-fat diet feeding were lower in rodents treated with CYR119 than in those treated with vehicle.

Conclusions

These data suggest that sGC stimulation could provide neuroprotective effects by attenuating inflammatory responses in nonclinical models of neuroinflammation.
Serious physical assault and subsequent risk for rehospitalization in individuals with severe mental illness: a nationwide, register-based retrospective cohort study
Authors: Mlada Karolina , Formanek Tomas , Vevera Jan , Latalova Klara , Winkler Petr , Volavka Jan
Published: September 2021

Background

Victimization is associated with worse social and clinical outcomes of individuals with severe mental illness (SMI). A relapse of SMI may be one of the clinical consequences of assaultive trauma. As far as we know, there is no published study that analyzes nationwide health registers to assess the risk of SMI rehospitalization following assault.

Aim

We aimed to assess whether exposure to assault is associated with an increased risk of psychiatric hospitalization in those with SMI.

Methods

We utilized data from the Czech nationwide registers of all-cause hospitalizations and all-cause deaths. We defined exposed individuals as those discharged from a hospitalization for SMI between 2002 and 2007, and hospitalized for serious injuries sustained in an assault in the subsequent 7 years. For each assaulted individual, we randomly selected five counterparts, matched on SMI diagnosis, age and sex, who were not assaulted in the examined time period. We used mixed effect logistic regression to assess the effect of assault on the risk of SMI rehospitalization within the following 6 months. We fitted unadjusted models and models adjusted for the number of previous SMI hospitalizations and drug use disorders.

Results

The sample consisted of 248 exposed and 1 240 unexposed individuals. In the unadjusted model, assaulted individuals were almost four times more likely to be rehospitalized than their non-assaulted counterparts (odds ratio (OR) = 3.96; 95% CI 2.75; 5.71). After adjusting for all covariates, the OR remained threefold higher (OR = 3.07; 95% CI 2.10; 4.49).

Conclusion

People with a history of SMI hospitalization were approximately three times more likely to be rehospitalized for SMI within 6 months after an assault than their non-assaulted SMI counterparts. Soon after a person with SMI is physically assaulted, there should be a psychiatric evaluation and a close follow-up.
Safety of transanal ileal pouch-anal anastomosis for ulcerative colitis: a retrospective observational cohort study
Authors: Lask Aina , Biebl Matthias , Dittrich Luca , Fischer Andreas , Adler Andreas , Tacke Frank , Aigner Felix , Schmuck Rosa , Chopra Sascha , Knoop Michael , Pratschke Johann , Gül-Klein Safak
Published: September 2021

Background

Colectomy with transanal ileal pouch-anal anastomosis (taIPAA) is a surgical technique that can be used to treat benign colorectal disease. Ulcerative colitis is the most frequent inflammatory bowel disease (IBD) and although pharmacological therapy has improved, colectomy rates reach up to 15%. The objective of this study was to determine anastomotic leakage rates and treatment after taIPAA as well as short- and long-term pouch function.

Methods

We conducted a retrospective analysis of a prospective database of all patients undergoing taIPAA at an academic tertiary referral center in Germany, between 01/03/2015 and 31/08/2019. Patients with indications other than ulcerative colitis or with adjuvant chemotherapy following colectomy for colorectal carcinoma were excluded for short- and long-term follow up due to diverging postoperative care yet considered for evaluation of anastomotic leakage.

Results

A total of 22 patients undergoing taIPAA during the study time-window were included in analysis. Median age at the time of surgery was 32 ± 12.5 (14–54) years. Two patients developed an anastomotic leakage at 11 days (early anastomotic leakage) and 9 months (late anastomotic leakage) after surgery, respectively. In both patients, pouches could be preserved with a multimodal approach. Twenty patients out of 22 met the inclusion criteria for short and long term follow-up. Data on short-term pouch function could be obtained in 14 patients and showed satisfactory pouch function with only four patients reporting intermittent incontinence at a median stool frequency of 9–10 times per day. In the long-term we observed an inflammation or “pouchitis” in 11 patients and a pouch failure in one patient.

Conclusion

Postoperative complication rates in patients with benign colorectal disease remain an area of concern for surgical patient safety. In this pilot study on 22 selected patients, taIPAA was associated with two patients developing anastomotic leakage. Future large-scale validation studies are required to determine the safety and feasibility of taIPAA in patients with ulcerative colitis.
Are we sure that the neurological impact of COVID 19 in childhood has not been underestimated?
Authors: Principi Nicola , Esposito Susanna
Published: September 2021

Background

Presently, it is known that, even if less frequently than in adults, children can develop a severe new coronavirus disease 2019 (COVID-19). Children with the SARS-CoV-2 infection can have neurological signs and symptoms of disease more frequently than previously thought, revealing the involvement of the central nervous system, the peripheral nervous system, or both. Aim of this manuscript is to highlight the neurologic complications associated with SARS-CoV-2 among pediatric patients with COVID-19, suggesting when to monitor carefully neurologic development.

Main findings

Children with a severe chronic underlying disease, infants and toddlers and those who develop the so-called multisystem inflammatory syndrome (MIS-C) are those with the highest incidence of neurological complications. Fortunately, in most of the cases, neurological manifestations, mainly represented by headache and anosmia, are mild and transient and do not significantly complicate the COVID-19 course. However, in some cases, very severe clinical problems associated with relevant alterations of neuroimaging, electroencephalography, nerve conduction studies and electromyography findings can develop. Generally, almost all the children with COVID-19 and neurological manifestations till now described have made a complete recovery, although in some cases this has occurred after several weeks of treatment. Moreover, COVID-19 infection during pregnancy has been found associated with an increased risk of obstetric complications that can lead to neurological acute and long-term manifestations in neonates.

Conclusions

Based on data showing the neurologic impact of COVID-19 in pediatric age, we suggest monitoring neurological development a few months after healing in pediatric patients who have presented MIS-C, seizures or other neurological manifestations and in children of pregnant women with COVID-19 in order to detect overt and subtle deficits.
HLA-DRB1 risk alleles for RA are associated with differential clinical responsiveness to abatacept and adalimumab: data from a head-to-head, randomized, single-blind study in autoantibody-positive early RA
Authors: Rigby William , Buckner Jane H. , Louis Bridges S. , Nys Marleen , Gao Sheng , Polinsky Martin , Ray Neelanjana , Bykerk Vivian
Published: September 2021

Background

Certain risk alleles associated with autoantibody-positive rheumatoid arthritis (RA) have been linked to poorer prognoses. In patients with autoantibody-positive RA, abatacept shows differential efficacy to tumor necrosis factor inhibitors. Our aim was to investigate the relationship between clinical response to abatacept and to adalimumab and presence of risk alleles encoding human leukocyte antigen (HLA)-DRB1 shared epitope (SE) in RA.

Methods

In this head-to-head study, biologic-naïve adults with early (≤ 12 months), moderate-to-severe RA and inadequate response to methotrexate (MTX-IR), autoantibody-positive for both anti-cyclic citrullinated peptide 2 and rheumatoid factor, were randomized 1:1 to receive subcutaneous abatacept 125 mg weekly or subcutaneous adalimumab 40 mg every 2 weeks for 24 weeks with stable, weekly oral MTX. An open-label period to 48 weeks followed, during which adalimumab-treated patients were switched to abatacept. Patients were genotyped for HLA-DRB1 alleles and classified as SE-positive (≥ 1 SE allele) or SE-negative (no SE alleles). Efficacy was assessed at weeks 24 and 48.

Results

Forty patients each received abatacept (9 SE-negative, 30 SE-positive, one unknown) or adalimumab (9 SE-negative, 31 SE-positive). Mean age and disease duration were 46.0 years and 5.5 months, respectively. At week 24, a greater percentage of abatacept patients achieved 50% improvement in ACR criteria (ACR50) compared with adalimumab patients (73% vs 45%, respectively) and estimate of difference (95% confidence interval [CI]), 28 (5, 48). In SE-positive patients, ACR50 estimate of difference (95% CI) was 32 (7, 55). During the open-label period, responses were sustained in the abatacept non-switch group and showed trends toward further improvement in the adalimumab-to-abatacept switch group at week 48, in both the overall and the SE-positive subpopulation. No new safety signals were identified.

Conclusions

In MTX-IR patients with early, autoantibody-positive RA, abatacept resulted in numerically higher efficacy responses versus adalimumab after 24 weeks, with more pronounced treatment differences in SE-positive patients. After 48 weeks, responses were sustained in patients who continued abatacept while those who switched to abatacept showed further clinical improvement, overall, and in SE-positive patients. This supports co-stimulation blockade as an effective treatment strategy for patients with early, autoantibody-positive RA, particularly among SE-positive patients.

Trial registration

NIH US National Library of Medicine, NCT02557100. Registered on September 23, 2015.
Risk of rheumatoid arthritis diagnosis in statin users in a large nationwide US study
Authors: Peterson Madeline N. , Dykhoff Hayley J. , Crowson Cynthia S. , Davis John M. , Sangaralingham Lindsey R. , Myasoedova Elena
Published: September 2021

Objective

To evaluate the association between statin use and the risk of developing rheumatoid arthritis (RA) in a large, US case-control study.

Methods

Using the OptumLabs Data Warehouse, RA cases were identified as patients aged ≥18 years with ≥2 RA diagnoses between January 1, 2010 and June 30, 2019 and ≥1 prescription fills for methotrexate within 1 year of the first RA diagnosis. The first RA diagnosis was the index date. Cases were matched 1:1 to controls on age, sex, region, year of index date, and length of baseline coverage. Statin users were defined by having ≥2 statin prescription fills at least 90 days pre-index. Patients identified as statin users were further classified by statin user status (current or former), statin use duration, and intensity of statin exposure. Odds ratios for RA risk with statin use were estimated using logistic regression.

Results

16,363 RA cases and 16,363 matched controls were identified. Among RA cases, 5509 (33.7%) patients were statin users compared to 5164 (31.6%) of the controls. Statin users had a slightly increased risk of RA compared to non-users (OR 1.12, 95% CI 1.06–1.18), and former statin users had an increased RA risk compared to current users (OR 1.21, 95% CI 1.13–1.28). However, risk was eliminated following adjustment for hyperlipidemia. The risk estimates for statin use duration and intensity did not reach significance.

Conclusion

This study demonstrates no significant increase in the risk of developing RA for statin users compared to non-users after adjustment for hyperlipidemia in addition to other relevant confounders. However, more information from prospective studies would be necessary to further understand this relationship.
HbA1C variability among type 2 diabetic patients: a retrospective cohort study
Authors: Akselrod Dikla , Friger Michael , Biderman Aya
Published: September 2021

Background

Studies have found that HbA1C variability is an independent risk factor for diabetic complications in type 2 diabetic patients. This study aims to find factors contributing to higher HbA1C variability in the community.

Methods

The study was conducted in the southern district of Israel, in Clalit Health Services (CHS). The study population was type 2 diabetic individuals aged 40–70 years in 2005, with a follow-up period of 11 years, until 2015. The definition of HbA1C variability was done by the standard deviation from the average HbA1C value of the entire study period, which was calculated for each participant. The study population was divided into two groups, “variability group” with HbA1C SD > 1.2, and “comparison group” of participants with HbA1C SD ≤ 1.2. In the univariate analysis we used X2 or Fisher test for categorical variables and independent t-test for numeric continuous variables. In the multivariate analysis we used logistic regression as well as assessing for possible interactions. Statistical analysis was ascribed for p < 0.05. All the data was drawn from the computerized medical system used by all primary care physicians and nurses in CHS working in the community.

Results

The study population included 2866 participants, the average age was 58.6 years, 43.3% men and 56.7% women. Each participant had an average of 20.9 HbA1C measures in their computerized medical record during the 11 years of follow up. The mean HbA1C value was 7.8%. We found 632 patients (22%) with a high variability, whereas 2234 (78%) had a low variability of HbA1C. In the “variability group” there was a higher percentage of smokers, BMI ≥ 30 and a higher rate of visits to diabetic clinics compared to the “no variability” group. In the “variability group” we found a much higher use of insulin and ACE inhibitors. The highest frequency of variability was between HbA1c values of 8.1–8.5. The multivariate analysis showed that HbA1C variability was associated with insulin use (OR = 4.1, p < 0.001), with age (OR = 0.939, p < 0.001), and Ischemic heart disease (OR = 1.258, p = 0.03). BMI ≥ 30 was almost statistically significant (OR = 1.206, p = 0.063). Gender was statistically insignificant.

Conclusions

In conclusion, HbA1C variability might be used as an additional marker in Diabetes Mellitus type 2, reflecting the disease complexity characteristics and the patient’s lifestyle profile.
Current ankle sprain prevention and management strategies of netball athletes: a scoping review of the literature and comparison with best-practice recommendations
Authors: Rowe Patrick L. , Bryant Adam L. , Paterson Kade L.
Published: September 2021

Background

Ankle sprains are the most commonly reported injury in netball. Approximately four in five netball athletes will sustain an ankle sprain, up to half will go on to sustain recurrent ankle sprains, and nine in ten report perceived ankle instability. Historically, prevention and management strategies of ankle sprains and injuries have been investigated for a variety of sports, however, no literature reviews have investigated these in netball athletes, or compared these with current best-practice within the literature. Therefore, this scoping review aims to understand how netball athletes currently prevent and manage ankle sprains and to compare these approaches with best-practice recommendations.

Methods

A literature search was conducted using MEDLINE, CINAHL, and SPORTDiscus databases using keywords to capture studies with data or information related to the prevention and management of ankle sprains and injuries in netball.

Results

The search strategy captured 982 studies across all databases, with 30 netball studies included in this scoping review. Studies suggest netball athletes are not commonly referred to health professionals, do not undertake adequate rehabilitation, and almost immediately return to court following an ankle sprain or injury. Current best-practices suggest injury prevention programs and external ankle support effectively reduce ankle sprains and injuries; however, poor compliance and implementation may be a significant barrier. Currently, there is a lack of evidence that netball-specific footwear reduces the risk of ankle sprains.

Conclusion

The findings suggest netball athletes do not implement current best-practice prevention and management strategies following an ankle sprain. This is despite evidence of the effectiveness of injury prevention programs, external ankle support, and adequate rehabilitation in reducing ankle sprain rates. Current-best practice prevention and management of ankle sprains should be considered by clinicians, coaches, and athletes to reduce the prevalence and chronicity of ankle sprains in netball.
Mitigating the noisy solution impact of mixed Gibbs sampling detector in high-order modulation large-scale MIMO systems
Authors: Mussi Alex M. , Abrão Taufik
Published: September 2021

A neighborhood-restricted mixed Gibbs sampling (MGS)-based approach is proposed for low-complexity high-order modulation large-scale multiple-input multiple-output (LS-MIMO) detection. The proposed LS-MIMO detector applies a neighborhood limitation (NL) on the noisy solution from the MGS at a distanced— thus, namedd-simplified MGS (d-sMGS) — in order to mitigate its impact, which can be harmful when a high-order modulation is considered. Numerical simulation results considering 64-QAM demonstrated that the proposed detection method can substantially improve the MGS algorithm convergence, whereas no extra computational complexity per iteration is required. The proposedd-sMGS-based detector suitable for high-order modulation LS-MIMO further exhibits improved performance × complexity tradeoff when the system loading is high, i.e., when$\frac {K}{N}\geq 0.75$KN≥0.75. Also, with increasing the number of dimensions, i.e., increasing number of antennas and/or modulation order, a smaller restriction of 2-sMGS was shown to be a more interesting choice than 1-sMGS.
Prevalence and predictors of hepatitis B virus (HBV) infection in east Africa: evidence from a systematic review and meta-analysis of epidemiological studies published from 2005 to 2020
Authors: Kafeero Hussein Mukasa , Ndagire Dorothy , Ocama Ponsiano , Kudamba Ali , Walusansa Abdul , Sendagire Hakim
Published: September 2021

Background

The epidemiology of hepatitis B virus (HBV) in the general population in east Africa is not well documented. In this meta-analysis, we examined 37 full published research articles to synthesise up-to-date data on the prevalence and predictors of the HBV burden for the effective prevention and management of the virus in our region.

Methods

We examined 37 full published research articles found using PubMed, Scopus, African Journal Online (AJOL), and Google Scholar between May and October 2020. Dichotomous data on HBV prevalence and predictors of infection were extracted from the individual studies. The HBV prevalence, test of proportion, relative risk, and I2statistics for heterogeneity were calculated using MedCalc software version 19.1.3. Begg’s tests was used to test for publication bias. Sources of heterogeneity were analysed through sensitivity analysis, meta-regression, and sub-group analysis at 95% CI.P < 0.05 was considered significant for all analyses.

Results

The prevalence of HBV was generally high (6.025%), with publications from Kenya (8.54%), Uganda (8.454%) and those from between 2011 and 2015 (8.759%) reporting the highest prevalence (P < 0.05). Blood transfusion, scarification, promiscuity, HIV seropositivity, and being male were independent predictors significantly associated with HBV infection (P < 0.05), with the male sex being the most strongly associated predictor of HBV infection. Meta-regressions for the pooled HBV prevalence and sample size, as well as the year of publication, lacked statistical significance (P > 0.05). Omitting the study with the largest sample size slightly increased pooled HBV prevalence to 6.149%, suggesting that the studies are robust. Begg’s test showed no evidence of publication bias for overall meta-analysis (p > 0.05).

Conclusion

The burden of HBV is still high, with the male sex, blood transfusion, body scarification, and HIV seropositivity being potential predictors of infection. Thus, it is important to scale up control and prevention measures targeting persons at high risk.
Large- and small-scale movement and distribution of acoustically tagged lake sturgeon (Acipenser fulvescens) in eastern Lake Erie
Authors: Withers Jonah L. , Takade-Heumacher Helen , Davis Lori , Neuenhoff Rachel , Albeke Shannon E. , Sweka John A.
Published: September 2021

Background

Defining the spatial distribution, home range, and movement patterns of lake sturgeon (Acipenser fulvescens) is important to managers and decision-makers given the large migration potential and potamodromous behavior exhibited by the species. A remnant population of lake sturgeon remains in the far eastern basin of Lake Erie and although recent efforts have estimated the population size, described the age distribution, and identified a primary spawning site no study to date has examined the spatial distribution or movements of individuals within this population. Between 2014 and 2018, we acoustically tagged 59 adult lake sturgeon, captured in the Buffalo Harbor area, and monitored their large-scale movements throughout Lake Erie with the Great Lakes Acoustic Telemetry System and small-scale movements with a Vemco Positioning System in the Buffalo Harbor area. After dividing Lake Erie into seven sections, we ran a multi-state mark–recapture model to examine the movement rates into and out of the eastern most section of the lake. Within a heavily utilized lake section, in the Buffalo Harbor area, we identified home ranges with our Vemco Positioning System for each season and year using averaged Brownian bridge movement models.

Results

Although some sturgeon demonstrated large-scale movements, traversing the entirety of Lake Erie, the majority of individuals spent their time in the eastern basin of the lake. Home ranges appeared to vary among seasons, but were consistent across years with lake sturgeon selecting the northeastern, rocky, and shallow area of our array during pre-spawning and spawning seasons and leaving our array, or selecting a trough running along the northwestern portion of our array comprising sand and bedrock, in the summer and fall seasons.

Conclusions

Documenting these large-scale movements aligns with previous findings that lake sturgeon on either end of the lake are genetically similar and demonstrates lake sturgeon in the eastern basin exhibit strong philopatry. Our small-scale movement models provide managers with spatial reference points, in the form of utilization distributions, indicating heavily used areas by lake sturgeon within seasons. Future studies should examine what parameters are driving site selection in these areas.
How FGF23 shapes multiple organs in chronic kidney disease
Authors: Leifheit-Nestler Maren , Haffner Dieter
Published: September 2021

Chronic kidney disease (CKD) is associated with distinct alterations in mineral metabolism in children and adults resulting in multiple organ dysfunctions. Children with advanced CKD often suffer from impaired bone mineralization, bone deformities and fractures, growth failure, muscle weakness, and vascular and soft tissue calcification, a complex which was recently termed CKD-mineral and bone disorder (CKD-MBD). The latter is a major contributor to the enhanced cardiovascular disease comorbidity and mortality in these patients. Elevated circulating levels of the endocrine-acting phosphaturic hormone fibroblast growth factor (FGF) 23 are the first detectable alteration of mineral metabolism and thus CKD-MBD. FGF23 is expressed and secreted from osteocytes and osteoblasts and rises, most likely due to increased phosphate load, progressively as kidney function declines in order to maintain phosphate homeostasis. Although not measured in clinical routine yet, CKD-mediated increased circulating levels of FGF23 in children are associated with pathological cardiac remodeling, vascular alterations, and increased cognitive risk. Clinical and experimental studies addressing other FGF23-mediated complications of kidney failure, such as hypertension and impaired bone mineralization, show partly conflicting results, and the causal relationships are not always entirely clear. This short review summarizes regulators of FGF23 synthesis altered in CKD and the main CKD-mediated organ dysfunctions related to high FGF23 levels.
Dangers of residual confounding: a cautionary tale featuring cognitive ability, socioeconomic background, and education
Authors: Sorjonen Kimmo , Falkstedt Daniel , Wallin Alma Sörberg , Melin Bo , Nilsonne Gustav
Published: September 2021

Background

Cognitive ability and socioeconomic background (SEB) have been previously identified as determinants of achieved level of education. According to a “discrimination hypothesis”, higher cognitive ability is required from those with lower SEB in order to achieve the same level of education as those with higher SEB. Support for this hypothesis has been claimed from the observation of a positive association between SEB and achieved level of education when adjusting for cognitive ability. We propose a competing hypothesis that the observed association is due to residual confounding.

Methods

To adjudicate between the discrimination and the residual confounding hypotheses, data from the 1997 National Longitudinal Survey of Youth (NLSY97, N = 8984) was utilized, including a check of the logic where we switched predictor and outcome variables.

Results

The expected positive association between SEB and achieved level of education when adjusting for cognitive ability (predicted by both hypotheses) was found, but a positive association between cognitive ability and SEB when adjusting for level of education (predicted only by the residual confounding hypothesis) was also observed.

Conclusions

These results highlight the potential use of reversing predictors and outcomes to test the logic of hypothesis testing, and support a residual confounding hypothesis over a discrimination hypothesis in explaining associations between SEB, cognitive ability, and educational outcome.
Suture granuloma with hydronephrosis caused by ileostomy closure after rectal cancer surgery: a case report
Authors: Takano Yasuhiro , Haruki Koichiro , Tsukihara Shu , Abe Tadashi , Koyama Muneyuki , Ito Daisuke , Kanno Hironori , Son Kyonsu , Hanyu Nobuyoshi , Eto Ken
Published: September 2021

Background

Suture granuloma with hydronephrosis after abdominal surgery is extremely rare. We herein report a successfully treated case of suture granuloma with hydronephrosis caused by ileostomy closure after rectal cancer surgery.

Case presentation

A 63-year-old male underwent laparoscopic low anterior resection with covering ileostomy. Two months after primary operation, ileostomy closure was performed with two layered hand-sewn suture (Albert–Lembert method) using absorbable suture. In that operation, marginal blood vessels in the mesentery were ligated with silk suture. The patient had remained in remission with no evidence of tumor recurrence, however, 2 years and 5 months after primary surgery, a contrast-enhanced computed tomography (CT) scan showed a mass-forming lesion on the right external iliac artery (43 × 26 mm) and hydronephrosis. Positron emission tomography/computed tomography (PET/CT) showed a mass-forming lesion without high accumulation, which obstructed the right ureter. Recurrence could not be ruled out due to the rapid appearance of tumor and hydronephrosis in the short-term period. Thus, the patient underwent laparotomy. The tumor located in the mesentery near the anastomosis of ileostomy closure and it was strongly adherent to the retroperitoneum, which obstructed the right ureter. The adhesion between the tumor and ureter was carefully dissected and tumor resection with partial small bowel resection was then performed with preservation of the ureter using ureteral stents. Pathological examination of the tumor revealed fibrous proliferation of foreign body granuloma. In the resected tumor, sutures with foreign giant cells were found. Therefore, we diagnosed the tumor as silk suture granuloma, which was caused by the silk suture used to ligate blood vessels of the mesentery at the ileostomy closure. The patient remained well with no evidence of tumor recurrence as 5 years after the primary operation of rectal cancer.

Conclusions

Suture granuloma is a rare surgery-related complication in the postoperative surveillance of patients with colorectal cancer. If suture granuloma mimicking local recurrence is a differential diagnosis, it would be important to consider to avoid unnecessary extended resection.
Neurological complications after pediatric cardiac surgery
Authors: Arslanoğlu Ergin , Kara Kenan Abdurrahman , Yiğit Fatih , Arkan Cüneyt , Uslu Ufuk , Şavluk Ömer Faruk , Yılmaz Abdullah Arif , Tunçer Eylem , Çine Nihat , Ceyran Hakan
Published: September 2021

Background

The number of pediatric patients who survive open-heart surgery has increased in recent years and the complications seen in this patient group continue to decrease with each technological advance, including new surgical and neuroprotective techniques and the improvement in surgeons’ experience with this patient population. However, neurological complications, which are the most feared and difficult to manage, require long-term follow-up, and increase hospital costs remain a leading cause of mortality and morbidity in this cohort.

Results

We evaluated the neurological physical examination, cranial computed tomography (CT), and magnetic resonance (MRI) records of 162 pediatric patients with neurological symptoms lasting more than 24 h after undergoing heart surgery in our clinic between June 2012 and May 2020. The patients’ ages ranged from 0 to 205 months, with a mean of 60.59 ± 46.44 months.

Of the 3849 pediatric cardiac surgery patients we screened, 162 had neurological complications in the early period (the first 10 days after surgery). The incidence was calculated as 4.2%; 69 patients (42.6%) experienced seizures, 17 (10.5%) experienced confusion, 39 (24.1%) had stupor, and 37 (22.8%) had hemiparesis. Of the patients who developed neurological complications, 54 (33.3%) died. Patients with neurological complications were divided into 3 groups: strokes (n = 90), intracranial bleeding (n = 37), and no radiological results (n = 35). Thirty-four patients (37.8%) in the stroke group died, as did 15 (40%) in the bleeding group, and 5 (14.3%) in the no radiological results group.

Conclusions

Studies on neurological complications after pediatric heart surgery in the literature are currently insufficient. We think that this study will contribute to a more detailed discussion of the issue. Responses to neurological events and treatment in the pediatric group may differ compared to the adult age group. Primary prevention methods should be the main approach in combating neurological complications; their formation mechanisms should be carefully monitored and preventive treatment strategies should be developed.