bluuebunny/crossref_metadata_2025_split huggingface dataset:
An immunologist's perspective on anti-COVID-19 vaccines
Authors: Milota Tomas , Strizova Zuzana , Smetanova Jitka , Sediva Anna 
Published: September 2021

Purpose of review
Antisevere acute respiratory syndrome-corona virus 2 (SARS-CoV-2) vaccines may provide prompt, effective, and safe solution for the COVID-19 pandemic. Several vaccine candidates have been evaluated in randomized clinical trials (RCTs). Furthermore, data from observational studies mimicking real-life practice and studies on specific groups, such as pregnant women or immunocompromised patients who were excluded from RCTs, are currently available. The main aim of the review is to summarize and provide an immunologist's view on mechanism of action, efficacy and safety, and future challenges in vaccination against SARS-CoV-2.

Recent findings
mRNA and recombinant viral vector-based vaccines have been approved for conditional use in Europe and the USA. They show robust humoral and cellular responses, high with efficacy in prevention of COVID-19 infection (66.9 95%) and favorable safety profile in RCTs. High efficacy of 80–92% was observed in real-life practice. A pilot study also confirmed good safety profile of the mRNA vaccines in pregnant women. Unlike in those with secondary immunodeficiencies where postvaccination responses did not occur, encouraging results were obtained in patients with inborn errors of immunity.

Summary
Although both RCTs and observational studies suggest good efficacy and safety profiles of the vaccines, their long-term efficacy and safety are still being discussed. Despite the promising results, clinical evidence for specific groups such as children, pregnant and breastfeeding women, and immunocompromised patients, and for novel virus variants are lacking.

Video abstract

http://links.lww.com/COAI/A21.
Human factors affecting intraoperative patient safety
Authors: De Hert Stefan 
Published: September 2021

Purpose of review
This review addresses the importance of some of the human factors for intraoperative patient safety with particular focus on the active failures. These are the mishaps or sentinel events related to decisons taken and actions performed by the individual at the delivery end of a system. Such sentinel events may greatly affect intraoperative patient safety.

Recent findings
Intimidating, aggressive and disruptive communication is a cause of adverse staff interaction, which may then represent an important patient safety threat. Also, anaesthesiologist's physical and mental state and limitations may interfere with patient safety.

Summary
The concept of physician well being is multidimensional and includes factors related to each physician as an individual as well as to the working environment. Creating optimal safe conditions for patients, therefore, requires actions at both the personal level and the working conditions. Also, initiatives to ban rude and dismissive communication should be implemented in order to further improve intraoperative patient safety.
Cost-effectiveness analysis of short versus long cephalomedullary nails for treatment of stable intertrochanteric femoral fractures: a theoretical cohort study
Authors: Fuller Carson C. , Kweon Christopher , Baker Timothy , Reese Carlie , Lack William D. 
Published: September 2021

Background:
Cephalomedullary nails are the current preferred method of fixation for the treatment of intertrochanteric fractures. Both short and long nails are currently used, and physician and institutional preferences are highly variable.

Methods:
Literature on intertrochanteric fracture types as categorized by the AO/Orthopaedic Trauma Association (AO/OTA) 31-A1, A2, and A3, was reviewed to determine failure rates requiring reoperation and health utility values. A decision-tree baseline followed by a Monte Carlo simulation was used to determine cost-effectiveness of each nail length at an incremental cost-effectiveness ratio threshold of $100,000 per quality-adjusted life-year. Procedural costs were derived from Medicare reimbursement rates and incremental costs of long nails were calculated using primary literature.

Results:
The model demonstrates short nails to be the more cost-effective implant. At the mean incremental long nail cost of $1,950 the short nail had an incremental cost-effectiveness ratio greater than $100,000/quality-adjusted life-year when the secondary fracture rate of short nails was at the mean value of 1.5%. At a short nail fracture rate greater than 2.4%, long nails were more cost-effective. In our theoretical cohort, a probabilistic sensitivity analysis demonstrated the short nail to be the cost-effective method 70% of the time at a willingness to pay of $100,000.

Conclusions:
Given the current reported failure ranges, short nails are the more cost-effective approach for the treatment of stable intertrochanteric femoral fractures. These conclusions are highly sensitive to the secondary fracture rate, which could confound our analysis because of limitations in length and quality of follow-up in the available primary literature.

Level of Evidence:
Level III.
Complications With Surgical Treatment of Pediatric Supracondylar Humerus Fractures: Does Surgeon Training Matter?
Authors: Sullivan Mikaela H. , Stillwagon Matthew R. , Nash Alysa B. , Jiang Huijun , Lin Feng-Chang , Chen Andrew T. , Louer Craig R. 
Published: September 2021

Introduction:
National trends reveal increased transfers to referral hospitals for surgical management of pediatric supracondylar humerus (SCH) fractures. This is partly because of the belief that pediatric orthopaedic surgeons (POs) deliver improved outcomes compared with nonpediatric orthopaedic surgeons (NPOs). We compared early outcomes of surgically treated SCH fractures between POs and NPOs at a single center where both groups manage these fractures.

Methods:
Patients ages 3 to 10 undergoing surgery for SCH fractures from 2014 to 2020 were included. Patient demographics and perioperative details were recorded. Radiographs at surgery and short-term follow-up assessed reduction. Primary outcomes were major loss of reduction (MLOR) and iatrogenic nerve injury (INI). Complications were compared between PO-treated and NPO-treated cohorts.

Results:
Three hundred and eleven fractures were reviewed. POs managed 132 cases, and NPOs managed 179 cases. Rate of MLOR was 1.5% among POs and 2.2% among NPOs (P=1). Rate of INI was 0% among POs and 3.4% among NPOs (P=0.041). All nerve palsies resolved postoperatively by mean 13.1 weeks. Rates of reoperation, infection, readmission, and open reduction were not significantly different. Operative times were decreased among POs (38.1 vs. 44.6 min; P=0.030). Pin constructs were graded as higher quality in the PO group, with a higher mean pin spread ratio (P=0.029), lower rate of “C” constructs (only 1 “column” engaged; P=0.010) and less frequent crossed-pin technique (P<0.001). Multivariate analysis revealed minimal positive associations only for operative time with MLOR (odds ratio=1.021; P=0.005) and INI (odds ratio=1.048; P=0.009).

Conclusions:
Postsurgical outcomes between POs and NPOs were similar. Rates of MLOR were not different between groups, despite differences in pin constructs. The NPO group experienced a marginally higher rate of INI, though all injuries resolved. Pediatric subspecialty training is not a prerequisite for successfully treating SCH fractures, and overall value of orthopaedic care may be improved by decreasing transfers for these common injuries.

Level of Evidence:
Level III—retrospective cohort study.
Should Q-CT Be the Gold Standard for Detecting Spinal Osteoporosis?
Authors: Kulkarni Arvind G. , Thonangi Yeshwanth , Pathan Sharukh , Gunjotikar Sharvari , Goparaju Praveen , Talwar Inder , Jaggi Sunila , Shah Sonali , Shah Neha , Kursija Girish 
Published: September 2021

Study Design.
Prospective comparative study.

Objective.
Refinement of the guidelines for screening of osteoporosis and considering quantitative computed tomography (Q-CT) for detecting spinal osteoporosis.

Summary of Background Data.
Spinal osteoporosis is often underestimated and under-evaluated due to either lack of availability of the diagnostic modality or lack of awareness about the possibility of overestimation by dual X-ray absorptiometry (DXA) scan. There is a need for reconsidering osteoporosis evaluation with a site specific and patient specific inclination.

Methods.
Post-menopausal women that underwent bone mineral density (BMD) evaluation from January-2018 to December-2020 with either Q-CT or DXA were evaluated. Comparison studies of the distribution of age and T-scores of the bone densities obtained from the two study groups: age-matched, sex-matched, and common skeletal site of interest (L1-4 vertebrae) were performed. Mann–Whitney U test, correlation and regression analyses were performed and bell curves were plotted.

Results.
Of the 718 women evaluated, 447 underwent Q-CT and 271 underwent DXA. There was no significant difference among the age distribution of the two study groups (P-value > 0.05). The mean and mode T-scores obtained by Q-CT and DXA were found to be –2.71, –3.8 and –1.63, –1.7 respectively. A highly significant difference in the T-scores was observed in the Q-CT and DXA groups (P-value < 0.0001). Among those who were screened by Q-CT, 58.16% were osteoporotic, 37.58% were osteopenic, and 4.25% were normal. The respective percentages in the DXA group were 30.63%, 49.82%, and 19.55%.

Conclusion.
Q-CT provides more precise estimation of cancellous bone mineral density than DXA. With the reliance on DXA for spinal BMD estimation being questionable, new standards have to be established for spinal osteoporosis evaluation. Q-CT can be a better alternative to replace DXA as the gold standard for the evaluation of spinal osteoporosis.

Level of Evidence: 2
Insufficient Recovery From C5 Palsy Following Anterior Cervical Decompression and Fusion
Authors: Odate Seiichi , Shikata Jitsuhiko , Yamamura Satoru , Okahata Akinori , Kawaguchi Shinji , Tanaka Chiaki 
Published: September 2021

Study Design.
Retrospective study.

Objective.
To determine the risk factors for insufficient recovery from C5 palsy (C5P) following anterior cervical decompression and fusion (ADF).

Summary of Background Data.
Postoperative C5P is a frequent but unsolved complication following cervical decompression surgery. Although most patients gradually recover, some recover only partially. When we encounter new-onset C5P following ADF, the question that often arises is whether the palsy will sufficiently resolve.

Methods.
We retrospectively reviewed consecutive patients who underwent ADF at our institution. We defined C5P as postoperative deterioration of deltoid muscle strength by two or more grades determined by manual muscle testing (MMT). We evaluated the following demographic data: patient factors, surgical factors, and radiological findings. C5P patients were divided into two groups: sufficient recovery (MMT grade≧4) and insufficient recovery (MMT grade < 4). Each parameter was compared between the two groups.

Results.
Of 839 patients initially included in the study, 57 experienced new-onset C5P (6.8%). At the final follow-up (mean, 55 ± 17 months), 41 patients experienced sufficient recovery, whereas 16 (28%) still exhibited insufficient recovery. Compared with the sufficient recovery group, patients with insufficient recovery exhibited a higher decompression combination score, a larger anterior shift in preoperative cervical sagittal balance, less lordosis of the pre- and postoperative C4/C5 segment, more frequent stenosis at the C3/C4 segment, lower deltoid strength at C5P onset, more frequent co-occurrence of biceps weakness, greater postoperative expansion of the dura mater, and more frequent presence of postoperative T2 high-intensity areas. Multivariate analysis revealed that co-occurrence of biceps muscle weakness, less lordosis at the preoperative C4/C5 segment, and postoperative expansion of the dura mater were independent predictors of insufficient recovery.

Conclusion.
The combination of unfavorable conditions, such as potential spinal cord disorder, cervical malalignment, and excessive expansion of the dura mater after corpectomy, predicts insufficient recovery from C5P.

Level of Evidence: 4
Gallbladder disease and pancreatic cancer risk: a multicentric case-control European study
Authors: Rosato V. , Gómez-Rubio P. , Molina-Montes E. , Márquez M. , Löhr M. , O’Rorke M. , Michalski C. W. , Molero X. , Farré A. , Perea J. , Kleeff J. , Crnogorac-Jurcevic T. , Greenhalf W. , Ilzarbe L. , Tardón A. , Gress T. , Barberá V. M. , Domínguez-Muñoz E. , Muñoz-Bellvís L. , Balsells J. , Costello E. , Iglesias M. , Kong Bo , Mora J. , O’Driscoll D. , Poves I. , Scarpa A. , Ye W. , Hidalgo M. , Sharp L. , Carrato A. , Real F. X. , La Vecchia C. , Malats N. 
Published: September 2021

Background and aims:
The overall evidence on the association between gallbladder conditions (GBC: gallstones and cholecystectomy) and pancreatic cancer (PC) is inconsistent. To our knowledge, no previous investigations considered the role of tumour characteristics on this association. Thus, we aimed to assess the association between self-reported GBC and PC risk, by focussing on timing to PC diagnosis and tumour features (stage, location, and resection).

Methods:
Data derived from a European case-control study conducted between 2009 and 2014 including 1431 PC cases and 1090 controls. We used unconditional logistic regression models to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) adjusted for recognized confounders.

Results:
Overall, 298 (20.8%) cases and 127 (11.6%) controls reported to have had GBC, corresponding to an OR of 1.70 (95% CI 1.33–2.16). The ORs were 4.84 (95% CI 2.96–7.89) for GBC diagnosed <3 years before PC and 1.06 (95% CI 0.79–1.41) for ≥3 years. The risk was slightly higher for stage I/II (OR = 1.71, 95% CI 1.15–2.55) vs. stage III/IV tumours (OR = 1.23, 95% CI 0.87–1.76); for tumours sited in the head of the pancreas (OR = 1.59, 95% CI 1.13–2.24) vs. tumours located at the body/tail (OR = 1.02, 95% CI 0.62–1.68); and for tumours surgically resected (OR = 1.69, 95% CI 1.14–2.51) vs. non-resected tumours (OR = 1.25, 95% CI 0.88–1.78). The corresponding ORs for GBC diagnosed ≥3 years prior PC were close to unity.

Conclusion:
Our study supports the association between GBC and PC. Given the time-risk pattern observed, however, this relationship may be non-causal and, partly or largely, due to diagnostic attention and/or reverse causation.
Interaction between occupational exposure to diesel exhaust and tobacco smoking in determining lung cancer risk: a meta-analysis
Authors: Rizzello Emanuele , Denti Pompiani Ilaria , Violante Francesco , Boffetta Paolo 
Published: September 2021

Background
While an association between exposure to diesel exhaust (DE) and risk of lung cancer has been reported in several studies, its interaction with tobacco smoking in determining lung cancer risk is not well characterized. This study aims at performing a systematic review and meta-analysis of results of epidemiology studies on this.

Methods
Studies included in the systematic review were identified from PubMed, Scopus, and Embase, without limitation of year of publication or language. Two reviewers independently reviewed the studies and abstracted relevant data from selected studies, applied a customized quality assessment tool and calculated the relative risks (RRs) and 95% confidence intervals (CIs) for the interaction between DE exposure and tobacco smoking on a multiplicative scale. Next, a random-effects meta-analysis of the interaction RR was conducted.

Results
Seven studies were included in the meta-analysis, of which two were cohort and five case-control studies. Results on the interaction were heterogeneous (I
2 = 45.6%). The summary RR for interaction was 0.79 (95% CI, 0.42–1.46). There was no indication of publication bias. There was no increased risk of lung cancer among non-smoking workers exposed to DE.

Conclusions
This meta-analysis suggested a less-than-multiplicative effect between DE exposure and tobacco smoking in determining lung cancer risk, but the hypothesis of multiplicative interaction cannot be rejected. The small number of relevant studies and the high heterogeneity among them prevent from definite conclusions.
Regional variability of melanoma incidence and prevalence in Hungary. Epidemiological impact of ambient UV radiation and socioeconomic factors.
Authors: Janka Eszter A. , Ványai Beatrix , Dajnoki Zsolt , Szabó Imre L. , Reibl Dániel , Komka Ida , Blasszauer Celia , Várvölgyi Tünde , Szegedi Andrea , Emri Gabriella 
Published: September 2021

Background
The incidence of cutaneous melanoma has risen faster than almost any other type of cancer in the last 50 years. Ultraviolet (UV) radiation and genetic susceptibility are the most important risk factors.

Objective
We aimed to determine the epidemiologic indicators of melanoma in Hungary, a country with an estimated population of 9.8 million and an area of 93 030 km2.

Methods
Anonymized patient records from the National Health Insurance Fund Management covering the entire population were used to determine the incidence and prevalence of melanoma in the counties of Hungary from 2013 to 2017. Altogether 20 030 melanoma cases were identified for inclusion in this study.

Results
The prevalence of melanoma increased over the investigated period and was significantly higher among women than men. The incidence of melanoma stagnated during this period and the incidence rate was the highest among the elderly. Interestingly, the incidence was higher in males in the elderly population, while the incidence was higher in females in the younger (<60 years) population. Geographical variations in ambient UV radiation did not show statistically significant correlation with the regional variability of epidemiologic indicators, probably due to small differences in the number of bright sunshine hours per year between regions. Although Hungary is a relatively small country, we observed regional heterogeneity in socioeconomic factors. Notably, a significant and strong negative correlation was found between single-person household rates and melanoma prevalence.

Conclusion
In addition to ambient UV radiation, melanoma incidence and prevalence appear to be related to age, gender and socioeconomic factors.
AEOL 10150 Alleviates Radiation-induced Innate Immune Responses in Non-human Primate Lung Tissue
Authors: Cui Wanchang , Zhang Pei , Hankey Kim G. , Xiao Mang , Farese Ann M. , MacVittie Thomas J. 
Published: September 2021

Abstract
To study the molecular and cellular mechanisms of radiation-induced lung injury (RILI) in a non-human primate model, Rhesus macaques were irradiated with lethal doses of radiation to the whole thorax. A subset of the irradiated animals was treated with AEOL 10150, a potent catalytic scavenger of reactive oxygen and nitrogen species. Lung tissues were collected at necropsy for molecular and immunohistochemical (IHC) studies. Microarray expression profiling in the irradiated lung tissues identified differentially expressed genes (DEGs) and pathways important in innate immunity. The elevated expression of cytokines (CCL2, CCL11, IL-8), complement factors (CFB, C3), apoptosis-related molecules (p53, PTEN, Bax, p21, MDM2, c-Caspase 3), and adhesion molecules (fibronectin, integrin β6, ICAM-1) were further studied using real-time PCR, Western blot, or IHC. Oxidative stress and pulmonary inflammatory cell infiltration were increased in the irradiated lungs. Treatment with AEOL 10150 significantly decreased oxidative stress and monocyte/macrophage infiltration. Cytokine/chemokine-induced excessive innate immune response after thoracic irradiation plays an important role in RILI. To our knowledge, this is the first study to highlight the role of cytokine/chemokine-induced innate immune responses in radiation-induced pulmonary toxicity in a NHP model.
Complementary Lipidomic, Proteomic, and Mass Spectrometry Imaging Approach to the Characterization of the Acute Effects of Radiation in the Non-human Primate Mesenteric Lymph Node after Partial-body Irradiation with Minimal Bone Marrow Sparing
Authors: Muller Ludovic , Huang Weiliang , Jones Jace W. , Farese Ann M. , MacVittie Thomas J. , Kane Maureen A. 
Published: September 2021

Abstract
Radiation sequelae is complex and characterized by multiple pathologies, which occur over time and nonuniformly throughout different organs. The study of the mesenteric lymph node (MLN) due to its importance in the gastrointestinal system is of particular interest. Other studies have shown an immediate post-irradiation reduction in cellularity due to the known effects of irradiation on lymphoid cell populations, but the molecular and functional mechanisms that lead to these cellular alterations remain limited. In this work, we show the use of lipidomic, proteomic, and mass spectrometry imaging in the characterization of the effects of acute radiation exposure on the MLN at different time points after ionizing radiation (IR) from 4 d to 21 d after 12 Gy partial body irradiation with 2.5% bone marrow sparing. The combined analyses showed a dysregulation of the lipid and protein composition in the MLN after IR. Protein expression was affected in numerous pathways, including pathways regulating lipids such as LXR/RXR activation and acute phase response. Lipid distribution and abundance was also affected by IR in the MLN, including an accumulation of triacylglycerides, a decrease in polyunsaturated glycerophospholipids, and changes in polyunsaturated fatty acids. Those changes were observed as early as 4 d after IR and were more pronounced for lipids with a higher concentration in the nodules and the medulla of the MLN. These results provide molecular insight into the MLN that can inform on injury mechanism in a non-human primate model of the acute radiation syndrome of the gastrointestinal tract. Those findings may contribute to the identification of therapeutic targets and the development of new medical countermeasures.
Metabolomics of Multiorgan Radiation Injury in Non-human Primate Model Reveals System-wide Metabolic Perturbations
Authors: Kumar Praveen , Wang Pengcheng , Farese Ann M. , MacVittie Thomas J. , Kane Maureen A. 
Published: September 2021

Abstract
Exposure to ionizing radiation following a nuclear or radiological incident results in potential acute radiation syndromes causing sequelae of multi-organ injury in a dose- and time-dependent manner. Currently, medical countermeasures against radiation injury are limited, and no biomarkers have been approved by regulatory authorities. Identification of circulating plasma biomarkers indicative of radiation injury can be useful for early triage and injury assessment and in the development of novel therapies (medical countermeasures). Aims of this study are to (1) identify metabolites and lipids with consensus signatures that can inform on mechanism of injury in radiation-induced multi-organ injury and (2) identify plasma biomarkers in non-human primate (NHP) that correlate with tissues (kidney, liver, lung, left and right heart, jejunum) indicative of radiation injury, assessing samples collected over 3 wk post-exposure to 12 Gy partial body irradiation with 2.5% bone marrow sparing. About 180 plasma and tissue metabolites and lipids were quantified through Biocrates AbsoluteIDQ p180 kit using liquid chromatography and mass spectrometry. System-wide perturbations of specific metabolites and lipid levels and pathway alterations were identified. Citrulline, Serotonin, PC ae 38:2, PC ae 36:2, and sum of branched chain amino acids were identified as potential biomarkers of radiation injury. Pathway analysis revealed consistent changes in fatty acid oxidation and metabolism and perturbations in multiple other pathways.