Significant Risk
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2021 ◽  
Hiroaki Ikesue ◽  
Kohei Doi ◽  
Mayu Morimoto ◽  
Masaki Hirabatake ◽  
Nobuyuki Muroi ◽  

Abstract Purpose: This study evaluated the risk of medication-related osteonecrosis of the jaw (MRONJ) in patients with cancer who received denosumab or zoledronic acid (ZA) for treating bone metastasis.Methods: The medical records of patients were retrospectively reviewed. Patients who did not undergo a dental examination at baseline were excluded. The primary endpoint was a comparison of the risk of developing MRONJ between the denosumab and ZA groups. Propensity score matching was used to control for baseline differences between patient characteristics and compare outcomes for both groups.Results: Among the 799 patients enrolled, 58 (7.3%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the ZA group (9.6% [39/406] vs. 4.8% [19/393], p = 0.009). Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.65–5.25; p < 0.001) and tooth extraction after starting ZA or denosumab (HR, 4.26; 95% CI, 2.38–7.44; p < 0.001) were significant risk factors for MRONJ. Propensity score-matched analysis confirmed that the risk of developing MRONJ was significantly higher in the denosumab group than in the ZA group (HR, 2.34; 95% CI, 1.17–5.01; p = 0.016). Conclusion: The results of this study suggest that denosumab poses a significant risk for developing MRONJ in patients treated for bone metastasis, and thus these patients require close monitoring.

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4582
Michael A. Trebino ◽  
Rahul D. Shingare ◽  
John B. MacMillan ◽  
Fitnat H. Yildiz

Biofilms, the predominant growth mode of microorganisms, pose a significant risk to human health. The protective biofilm matrix, typically composed of exopolysaccharides, proteins, nucleic acids, and lipids, combined with biofilm-grown bacteria’s heterogenous physiology, leads to enhanced fitness and tolerance to traditional methods for treatment. There is a need to identify biofilm inhibitors using diverse approaches and targeting different stages of biofilm formation. This review discusses discovery strategies that successfully identified a wide range of inhibitors and the processes used to characterize their inhibition mechanism and further improvement. Additionally, we examine the structure–activity relationship (SAR) for some of these inhibitors to optimize inhibitor activity.

Children ◽  
2021 ◽  
Vol 8 (8) ◽  
pp. 646
Emil Carlsson ◽  
Michael W. Beresford ◽  
Athimalaipet V. Ramanan ◽  
Andrew D. Dick ◽  
Christian M. Hedrich

Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease. The development of associated uveitis represents a significant risk for serious complications, including permanent loss of vision. Initiation of early treatment is important for controlling JIA-uveitis, but the disease can appear asymptomatically, making frequent screening procedures necessary for patients at risk. As our understanding of pathogenic drivers is currently incomplete, it is difficult to assess which JIA patients are at risk of developing uveitis. Identification of specific risk factors for JIA-associated uveitis is an important field of research, and in this review, we highlight the genomic, transcriptomic, and proteomic factors identified as potential uveitis risk factors in JIA, and discuss therapeutic strategies.

Neelotparna Saikia ◽  
Sukalyan Halder ◽  
Punam Jain

Cornual ectopic pregnancy accounts for 2-4% of all the ectopic pregnancies with a mortality rate 6-7 times higher than that of the ectopics in general. It is a diagnostic and therapeutic challenge to the clinician with a significant risk of rupturing and bleeding. As of yet, the incidence of recurrent cornual ectopic pregnancies is unknown. This report described the case of a patient who developed two cornual ectopic pregnancies within a span of 3 years with an intervening full term normal vaginal delivery. The 1st cornual ectopic was successfully managed by laparoscopic resection, which was followed by an uneventful postoperative course. The following contralateral cornual ectopic was managed by laparotomy since the patient presented with large hemoperitoneum.

2021 ◽  
Vol 8 ◽  
Kai He ◽  
Mengyu Liao ◽  
Yun Zhu ◽  
Bohao Cui ◽  
Haoyu Chen ◽  

Band keratopathy (BK) is a common complication in aphakic eyes with silicone oil tamponade for open-globe injury (OGI), characterized by the grayish-white opacities in the cornea, resulting in a significantly decreased vision when extending to the visual axis. To identify the risk factors for BK in aphakic eyes following vitreoretinal surgical treatment with silicone oil tamponade for OGIs, we performed a multicenter case-control study. The incidence of BK was 28% (28/100 eyes). The multivariate binary logistic regression revealed the silicone oil retention time (SORT) ≥6 months and zone III injury were significant risk factors for BK. From the hierarchical interaction, SORT ≥6 months had a significant risk for BK in eyes with rupture, aniridia, and zone III injury, while zone III injury had a significant risk for BK in eyes with rupture, incomplete/complete iris, and SORT ≥6 months. By using restricted cubic splines with three knots at the 25th, 50th, and 75th centiles to model the association of SORT with BK, we also found a marked increase in the risk for BK at ≥10 months and a slow increase after 6 months, but almost stable within 4–6 months.

2021 ◽  
Wei-Yu Lin ◽  
Sarah Fordham ◽  
Eric Hungate ◽  
Nicola Sunter ◽  
Claire Elstob ◽  

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we performed a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identified a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 x 10-8; KMT5B). We also identified a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N=1287) at 6p21.32 (rs3916765; P = 1.51 x 10 -10; HLA). Our results inform on AML etiology by identifying putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).

2021 ◽  
Vol 22 (1) ◽  
Jack S Bell ◽  
Benjamin D James ◽  
Saif Al-Chalabi ◽  
Lynne Sykes ◽  
Philip A Kalra ◽  

Abstract Background Acute kidney injury (AKI) is a recognised complication of coronavirus disease 2019 (COVID-19), yet the reported incidence varies widely and the associated risk factors are poorly understood. Methods Data was collected on all adult patients who returned a positive COVID-19 swab while hospitalised at a large UK teaching hospital between 1st March 2020 and 3rd June 2020. Patients were stratified into community- and hospital-acquired AKI based on the timing of AKI onset. Results Out of the 448 eligible patients with COVID-19, 118 (26.3 %) recorded an AKI during their admission. Significant independent risk factors for community-acquired AKI were chronic kidney disease (CKD), diabetes, clinical frailty score and admission C-reactive protein (CRP), systolic blood pressure and respiratory rate. Similar risk factors were significant for hospital-acquired AKI including CKD and trough systolic blood pressure, peak heart rate, peak CRP and trough lymphocytes during admission. In addition, invasive mechanical ventilation was the most significant risk factor for hospital-acquired AKI (adjusted odds ratio 9.1, p < 0.0001) while atrial fibrillation conferred a protective effect (adjusted odds ratio 0.29, p < 0.0209). Mortality was significantly higher for patients who had an AKI compared to those who didn’t have an AKI (54.3 % vs. 29.4 % respectively, p < 0.0001). On Cox regression, hospital-acquired AKI was significantly associated with mortality (adjusted hazard ratio 4.64, p < 0.0001) while community-acquired AKI was not. Conclusions AKI occurred in over a quarter of our hospitalised COVID-19 patients. Community- and hospital-acquired AKI have many shared risk factors which appear to converge on a pre-renal mechanism of injury. Hospital- but not community acquired AKI was a significant risk factor for death.

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1430
Vladimir Stevanovic ◽  
Irena Tabain ◽  
Tatjana Vilibic-Cavlek ◽  
Maja Mauric Maljkovic ◽  
Iva Benvin ◽  

Over a year into the COVID-19 pandemic, there is growing evidence that SARS-CoV-2 infections among dogs are more common than previously thought. In this study, the prevalence of SARS-CoV-2 antibodies was investigated in two dog populations. The first group was comprised of 1069 dogs admitted to the Veterinary Teaching Hospital for any given reason. The second group included dogs that shared households with confirmed COVID-19 cases in humans. This study group numbered 78 dogs. In COVID-19 infected households, 43.9% tested ELISA positive, and neutralising antibodies were detected in 25.64% of dogs. Those data are comparable with the secondary attack rate in the human population. With 14.69% of dogs in the general population testing ELISA positive, there was a surge of SARS-CoV-2 infections within the dog population amid the second wave of the pandemic. Noticeably seroprevalence of SARS-CoV-2 in the dog and the human population did not differ at the end of the study period. Male sex, breed and age were identified as significant risk factors. This study gives strong evidence that while acute dog infections are mostly asymptomatic, they can pose a significant risk to dog health. Due to the retrospective nature of this study, samples for viral isolation and PCR were unavailable. Still, seropositive dogs had a 1.97 times greater risk for developing central nervous symptoms.

Young-Chan Kim ◽  
Hyeongeun Kim ◽  
Jiwon Kwak ◽  
Hoyoung Lee ◽  
Kwang-Yoon Jung ◽  

Background and Objectives Oropharyngeal cancers (OPCs) can be staged down to a lower stage with p16 positivity and de-escalated therapy has been the common practice. The aim of this study is to evaluate the survival outcomes based on various clinical factors in advanced OPC patients. Subjects and Method A total of 58 OPC patients in the stage IVA based on the American Joint Committee on Cancer 7th edition were treated with primary surgery or primary chemoradiation therapy from 2010 to 2016. A survival analysis was carried out using the Kaplan- Meier method, log-rank test, and Cox proportional hazards model. Results The median follow-up was 39.5 months. Thirty-eight and 20 patients received surgery- based and radiation therapy (RT)-based treatments, respectively. Clinical T-stage and treatment method were significant risk factors for 5-year disease-free survival (DFS) rate, and the treatment method was the only significant risk factor for overall-survival (OS) rate. 5-year DFS rate in the surgery-based treatment and RT-based treatment was 76.1% and 36.0% (p=0.001). On multivariate analysis, the surgery-based treatment group was associated with a significantly reduced hazard of death [the hazard ratio (HR) for the radiation-based treatment was 6.565 compared to the surgery-based treatment, p=0.002]. 5-year OS rate in the surgery-based treatment and RT-based treatment was 91.1% and 53.4% (p=0.003), respectively. On the multivariate analysis, the surgery-based treatment group was associated with a significantly reduced hazard of death (the HR for the radiation-based treatment was 7.544 compared to the surgerybased treatment, p=0.012). Conclusion The primary surgery-based treatment for advanced OPC showed a better survival outcome than the primary radiation-based treatment, irrespective of p16 positivity.

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