bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of neutrophil-lymphocyte ratio and lactate dehydrogenase in melanoma patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis
Authors: Zhang Yongchao , Liu Bozhi , Kotenko Sergei , Li Wei 
Published: August 2022

Background:
Immune checkpoint inhibitors (ICIs) showed promising therapeutic efficacy on melanoma. Neutrophil-to-lymphocyte ratio (NLR) and serum lactate dehydrogenase (LDH) showed predictive values on prognosis of various tumors, but not on melanoma yet. This meta-analysis was conducted to investigate the prognostic role of NLR and LDH levels in melanoma treated with ICIs.

Methods:
A search was conducted for all reports published till March 2020 in PubMed, Web of Science, Cochrane Library, EMBASE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). Studies were included if they investigated the association between pretreatment NLR/LDH and prognosis in melanoma patients treated with ICIs. Subgroup analysis, publication bias, and meta-regression were conducted to investigate heterogeneity.

Results:
A total of 6817 melanoma patients were included. Overall, high pretreatment NLR and LDH were associated with poor overall survival (OS) (P < .001) and PFS (P < .001). Subgroup analyses revealed that elevated NLR and LDH levels were associated with poor OS and PFS in patients treated with anti-CTLA-4 or anti-PD-1/PD-L1 alone. NLR level was superior in predicting OS if compared with LDH level in patients treated with anti-PD-1/PD-L1 + anti-CTLA-4. In subgroup analysis stratified by cutoff value, high NLR level was associated with poor OS and PFS regardless of cutoff value, but LDH works when cutoff value = upper normal limit (UNL). The predictive value of NLR and LDH levels on OS and PFS was partially compromised in the Asian populations, compared with the Western countries.

Conclusion:
Blood NLR and LDH levels showed great potential to be used as early prognostic biomarkers in melanoma patients treated with ICIs.
Synchronous surgery and immediate reconstruction of double primary cancers of the ovary and breast
Authors: Huang Chao-Hsin , Kuo Yur-Ren , Chen Yu-Chieh , Shih Shen-Liang 
Published: August 2022

Introduction:
There has been an ongoing debate about the benefits and risks between synchronous surgery and two independent surgery of ovary tumor removal and breast reconstruction. Here we report a synchronous oncological surgery and immediate postmastectomy reconstruction of double primary cancers of the ovary and breast.

Patient concerns:
A 58-year-old woman presented with a right breast lump and ascites.

Diagnosis:
Computed tomography (CT) indicated synchronous breast and ovarian cancer with multiple metastases. Double primary mammary and ovarian cancer was confirmed after a series of evaluations, such as core needle biopsy of the breast tumor.

Interventions and outcomes:
Synchronous surgery and immediate reconstruction of double primary cancers of the ovary and breast were performed. Post-operative results showed complete resection of ovarian tumor, no post-operative complication, and excellent life quality.

Conclusion:
Synchronous surgery is warranted as a treatment option for selected cases of double primary cancer. The surgery not only achieved complete removal of one cancer and reduction of the other but also reached excellent breast reconstruction and body shape recovery.
Comparison of prediction accuracies between two mathematical models for the assessment of COVID-19 damage at the early stage and throughout 2020
Authors: Chuang Hua-Ying , Chien Tsair-Wei , Chou Willy , Wang Chen-Yu , Tsai Kang-Ting 
Published: August 2022

Background:
The negative impacts of COVID-19 (ImpactCOVID) on public health are commonly assessed using the cumulative numbers of confirmed cases (CNCCs). However, whether different mathematical models yield disparate results based on varying time frames remains unclear. This study aimed to compare the differences in prediction accuracy between 2 proposed COVID-19 models, develop an angle index that can be objectively used to evaluate ImpactCOVID, compare the differences in angle indexes across countries/regions worldwide, and examine the difference in determining the inflection point (IP) on the CNCCs between the 2 models.

Methods:
Data were downloaded from the GitHub website. Two mathematical models were examined in 2 time-frame scenarios during the COVID-19 pandemic (the early 20-day stage and the entire year of 2020). Angle index was determined by the ratio (=CNCCs at IP÷IP days). The R2 model and mean absolute percentage error (MAPE) were used to evaluate the model’s prediction accuracy in the 2 time-frame scenarios. Comparisons were made using 3 visualizations: line-chart plots, choropleth maps, and forest plots.

Results:
Exponential growth (EXPO) and item response theory (IRT) models had identical prediction power at the earlier outbreak stage. The IRT model had a higher model R2 and smaller MAPE than the EXPO model in 2020. Hubei Province in China had the highest angle index at the early stage, and India, California (US), and the United Kingdom had the highest angle indexes in 2020. The IRT model was superior to the EXPO model in determining the IP on an Ogive curve.

Conclusion:
Both proposed models can be used to measure ImpactCOVID. However, the IRT model (superior to EXPO in the long-term and Ogive-type data) is recommended for epidemiologists and policymakers to measure ImpactCOVID in the future.
Deciphering the molecular mechanism underlying the effects of epimedium on osteoporosis through system bioinformatic approach
Authors: Wu Keliang , Han Linjing , Zhao Ying , Xiao Qinghua , Zhang Zhen , Lin Xiaosheng 
Published: August 2022

Epimedium has gained widespread clinical application in Traditional Chinese Medicine, with the functions of promoting bone reproduction, regulating cell cycle and inhibiting osteoclastic activity. However, its precise cellular pharmacological therapeutic mechanism on osteoporosis (OP) remains elusive. This study aims to elucidate the molecular mechanism of epimedium in the treatment of OP based on system bioinformatic approach.
Predicted targets of epimedium were collected from TCMSP, BATMAN-TCM and ETCM databases. Differentially expressed mRNAs of OP patients were obtained from Gene Expression Omnibus database by performing Limma package of R software. Epimedium-OP common targets were obtained by Venn diagram package for further analysis. The protein-protein interaction network was constructed using Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were carried out by using clusterProfiler package. Molecular docking analysis was conducted by AutoDock 4.2 software to validate the binding affinity between epimedium and top 3 proteins based on the result of protein-protein interaction.
A total of 241 unique identified epimedium targets were screened from databases, of which 62 overlapped with the targets of OP and were considered potential therapeutic targets. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that these targets were positive regulation of cell cycle, cellular response to oxidative stress and positive regulation of cell cycle process as well as cellular senescence, FoxO, PI3K-Akt, and NF-kappa B signaling pathways. Molecular docking showed that epimedium have a good binding activity with key targets.
Our study demonstrated the multitarget and multi-pathway characteristics of epimedium on OP, which elucidates the potential mechanisms of epimedium against OP and provides theoretical basis for further drug development.
Total shoulder arthroplasty versus reverse total shoulder arthroplasty: Outcome comparison in osteoarthritis patients with or without concurrent rotator cuff deficiency
Authors: Liu Haifeng , Huang Tony Chieh-Ting , Yu Hanzhong , Wang Yicun , Wang Daping , Long Zeling 
Published: August 2022

Osteoarthritis (OA) is a common shoulder disorder that impacts shoulder functions. Shoulder arthroplasty is often required to restore function and quality of life. Reverse total shoulder arthroplasty (RSA), which was originally designed mainly for irreparable rotator cuff damage, has gained popularity in recent years for the treatment of advanced shoulder OA instead of the clinically standard total shoulder arthroplasty (TSA). However, this RSA has some nonnegligible flaws such as higher complications rate and economic cost, not mention the following problems caused by irreversible physical structural damage. Therefore, the employment of RSA needs to be carefully considered. This study aimed to compare TSA and RSA in OA patients with or without rotator cuff damage to better guide clinical decision making. We believe the radical use of RSA in patients without rotator cuff deficiency may cause more harm than good.
We queried the Nationwide Inpatient Sample (NIS) database from 2011 to 2014 to collect information on OA patients who received TSA and RSA. Patients were divided into 2 groups of comparison according to the presence of rotator cuff deficiency and matched with propensity score analysis.
A total of 57,156 shoulder arthroplasties were identified. RSA patients in the rotator cuff deficiency group had significant higher transfusion rates and longer hospital stays. RSA patients without rotator cuff deficiency had a statistically significantly higher number of implant-related mechanical complications, acute upper respiratory infections and postoperative pain. Overall, RSA incurred higher costs in both groups.
For OA patients with rotator cuff deficiencies, RSA has its benefits as complication rates were comparable to TSA. For those patients without rotator cuff deficiencies, the use of RSA should be reconsidered as there were more complications with higher severity.
Identify differential inflammatory cellular and serology pathways between children and adult patients in the lupus registry
Authors: Hsu Chung-Yuan , Chiu Wen-Chan , Huang Yi-Ling , Su Yu-Jih 
Published: August 2022

Background:
Age variances in systemic lupus erythematosus (SLE) may reflect different patterns and consequences. Monocyte differentiation is critical, and cytokine and chemokine milieu may be associated with long term outcome and treatment responses. This study aims to evaluate the inflammatory cellular and serology pathways associated with age in our lupus registry.

Methods:
We included patients with SLE and divided them into 2 groups according to age, ≤18 or >18 years old. We performed flow cytometry analysis to define the peripheral blood monocyte differentiation pattern and phenotypes and used the multiplex method to detect cytokine and chemokine panels. The results were then compared between the 2 subgroups.

Results:
In total, 47 SLE patients were included in this study. Of those, 23 patients were 18 years old or younger, and 24 patients were over the age of 18 years old. An increased distribution of circulating Type 2b macrophage (M2b) subsets was found in patients over 18 years old (P < 0.01), and we found the Type 1 macrophage (M1) to demonstrate a marked increase in those patients ≤18 years old (P = .05). Eotaxin values were significantly higher in patients >18 years old (P = .03), and Macrophage Inflammatory Protein (MIP)-1alpha, MIP-1beta, Interleukine (IL)-1Ra, Interferon (IFN)-alpha2, IL-12, IL-13, IL-17A, IL-1beta, IL-2, IL-4, IL-5, IL-7, IL-9, Monocyte Chemoattractant Protein (MCP)-3, Transforming Growth Factor (TGF)-alpha, and Tumor necrosis factor (TNF)-beta were significantly higher in patients ≤18 years old (all P < .05).

Conclusions:
We found significant M2b polarization in adult SLE patients, and several cytokines and chemokines were significantly higher in SLE patients ≤ 18 years old. Peripheral blood mononuclear cell differentiation and cytokine milieu could represent composite harm from both Type 2 helper T cells (Th2) and Type 17 helper T cells (Th17) pathways and may thus be a potential therapeutic target in younger SLE patients.
The role of internal fixation in the treatment of femoral head necrosis with ipsilateral hip fracture
Authors: Zhang Xinguo , Liu Sikai 
Published: August 2022

Whether internal fixation or hip arthroplasty is the most appropriate initial treatment for patients with ipsilateral hip fracture and osteonecrosis of the femoral head remains unknown. In this study, the prognoses of patients who underwent internal fixation or hip arthroplasty were analyzed and compared to explore the role of internal fixation in treating such patients.
We retrospectively reviewed 69 patients diagnosed with osteonecrosis of the femoral head and ipsilateral hip fracture from 1999 to 2018. They were divided into the hip arthroplasty or internal fixation group. The visual analog scale and Harris score were used. The incidence of complications and the conversion to arthroplasty were also investigated to further explore the role of internal fixation.
Male patients (male/female: 25/31 vs 20/38, P = .015), younger patients (average age: 46.80 ± 13.14 vs 61.07 ± 15.61, P < .001), and patients with femoral neck fractures (fracture type, femoral neck/trochanter: 21/31 vs 12/38, P = .003) were more likely to receive 1-stage hip arthroplasty. Of 38 patients undergoing internal fixation, fracture nonunion was identified in 9, and progression of osteonecrosis was identified in 16. Meanwhile, conversion to secondary hip arthroplasty occurred in 13 patients. Four independent risk factors for conversion to secondary hip arthroplasty were identified: age of ≤60 years (odds ratio [OR] = 9.786, 95% confidence interval [CI] = 2.735–35.015), male sex (OR = 6.790, 95% CI = 1.718–26.831), collapse of the femoral head before injury (OR = 7.170, 95% CI = 2.004–25.651), and femoral neck fracture (OR = 8.072, 95% CI = 2.153–30.261). A new scoring system was constructed for predicting conversion to hip arthroplasty in patients undergoing internal fixation treatment. A cutoff of ≤2 points indicated low risk for conversion, 3 to 4 points indicated moderate risk, and ≥5 points indicated high risk.
Patients who underwent internal fixation had worse prognoses than those who underwent 1-stage hip arthroplasty. However, in this study, hip arthroplasty conversion did not occur in most patients who received internal fixation. Using the new scoring system to identify patients who may require conversion to replacement may help make appropriate patient management and clinical decisions.
Correlation between endoscopic resection outcomes and endosonographic findings in gastric tumors with muscularis propria origin
Authors: Cho Jinwoong , Han Jihyun , Choi Mirim , Song Jaesun , Yang Mina , Lee Youngjae 
Published: August 2022

Endoscopic resection is an effective treatment for subepithelial tumors arising from the muscularis propria layer of the stomach. However, the invasion pattern revealed by the pathological examination of tumor specimens is often not consistent with the findings of preprocedural endoscopic ultrasounds (EUS).
We compared the real growing patterns of tumors, as evaluated on histopathological examination, with their EUS images, and analyzed the outcomes of endoscopic resections in relation to the EUS findings.
From January 2006 to June 2015, 32 patients underwent endoscopic resection for gastric tumors originating from the muscularis propria at our hospital.
We divided the patients into 3 groups according to the location of the tumor as diagnosed using pre procedural EUS: submucosa (group I, n = 5), muscularis propria (group II, n = 14), and tumors extending into the outer cavity (group III, n = 13).
Histopathological examination revealed 15 patients with gastrointestinal stromal tumors (GISTs), 14 with leiomyomas, and 3 with schwannomas. Accuracy of EUS in evaluating tumor invasion was 56%. Some tumors in groups I and II was removed by endoscopic submucosal dissection only. Muscular dissection was needed in 10 patients (71%) in group II and 9 patients (69%) in group III. Four patients (31%) in group III were found to have subserosal tumors. The complete resection rate was 88% (23 patients) among patients who underwent endoscopic submucosal dissection and endoscopic muscular dissection, and 67% (4 patients) among patients who underwent endoscopic subserosal dissection (ESSD). The tumor was completely removed in 12 patients (86%) in group II and 10 patients (77%) in group III.
EUS accurately predicts the layer of the subepithelial tumor in the stomach; however, the pattern of invasion of surrounding structures is difficult to evaluate using EUS.
Effect of low-dose lidocaine on MEPs in patients undergoing intracranial tumor resection with propofol anesthesia: A randomized controlled trial
Authors: Liu Meijuan , Wang Ning , Wang Dong , Liu Juan , Zhou Xuelong , Jin Wenjie 
Published: August 2022

Objective:
To investigate the effect of low-dose lidocaine on motor evoked potentials (MEPs) in patients undergoing intracranial tumor resection with propofol anesthesia.

Methods:
Forty patients who underwent intracranial tumor resection and required MEP monitoring were selected. They were randomly divided into the lidocaine group (group L, n = 20) and the control group (group C, n = 20) by computer-generated randomization. All patients were given propofol anesthesia under the guidance of the bispectral index. In group L, 1 mg/kg of lidocaine was injected intravenously during anesthesia induction. Then, lidocaine was continuously pumped at a speed of 1 mg/kg/h until the operation started. Group C was given an equal volume of normal saline. Heart rate (HR), mean artery pressure (MAP), and bispectral index were recorded before anesthesia induction (T0), 2 minutes after tracheal intubation (T1), and 35 minutes (T2), and 50 minutes (T3) after anesthesia induction. The amplitude and latency of MEP at T2 and T3, the total dosage of propofol after anesthesia induction, and adverse events before T3 were recorded.

Results:
Compared with those in group C, HR and MAP were significantly decreased at T1 in group L. No significant differences were observed in HR and MAP at T0, T2, and T3 between group L and group C. The total dosage of propofol and the incidence of adverse events were significantly lower in group L than in group C before T3. There were no significant differences in the amplitude and latency of MEP between the 2 groups at each time point.

Conclusions:
Low-dose lidocaine has no obvious effect on MEP in patients undergoing intracranial tumor resection. However, it increased hemodynamic stability, reduced propofol use, and decreased the incidence of adverse events.
Clinical application of bone turnover markers in treating osteoporotic vertebral compression fractures and their role in predicting fracture progression
Authors: Han Moon-Soo , Lee Gwang-Jun , Lee Seul-Kee , Lee Jung-Kil , Moon Bong Ju 
Published: August 2022

This study aimed to investigate whether changes in the bone turnover markers (BTMs) during teriparatide therapy for osteoporotic vertebral compression fractures could reflect therapeutic effects by analyzing the relationship between clinical and radiological features and BTMs.
A total of 33 patients with 51 osteoporotic vertebral compression fracture segments were included. Plain radiographs and BTM levels were evaluated at the pretreatment and at 3 months after teriparatide treatment. Based on serial vertebral compression ratio analysis, the progression of fracture was defined as a vertebral compression ratio decrease of ≥10%, relative to the pretreatment values.
All segments were divided into 2 groups: the “maintain” group with 32 (62.7%) segments and the “progression” group with 19 (37.3%) segments. After the teriparatide treatment, serum osteocalcin and serum C-terminal telopeptide of type I collagen levels (P = .028 and .008, respectively), and change amounts of them were significantly larger, increasing (P = .001) in the progression group. The vitamin D (25OH-D) levels were significantly lower (P = .038) in the progression group; however, the relative changes in the 25OH-D levels between the 2 groups, before and after the treatment, were not significantly different (P = .077). The parathyroid hormone (PTH) levels were reduced by the teriparatide treatment in both groups, while the decrease in PTH concentration after the treatment was significantly more pronounced in the progression group (P = .006). Significant increase in the osteocalcin and serum C-terminal telopeptide of type I collagen levels and a simultaneous decrease in the PTH levels during the teriparatide treatment suggest that clinicians should assume the progression of fracture.
A retrospective observational study of biomarker levels and severity assessment in pediatric community-acquired pneumonia
Authors: Bashir Anam , Khan Raheel , Thompson Stephanie , Caceres Manuel 
Published: August 2022

Multiple studies have investigated the role of biomarkers in predicting pneumonia severity in adults but minimal conclusive research exists for children. This study aimed to determine if the following biomarker levels, collected within 72 hours of hospital arrival: white blood cell count (WBC), platelet count, C-reactive protein (CRP), procalcitonin (PCT), neutrophil-lymphocyte ratio, neutrophil count, or band count associated with community-associated pneumonia (CAP) severity in children.

Methods:
A retrospective chart review was conducted on children (aged 60 days to 18 years) diagnosed with CAP, and admitted to a regional, tertiary hospital (Charleston, WV, USA) for 3 years (2015–2018). Patients were stratified into 2 severity cohorts, mild (no ICU care), and moderate/severe (required ICU care). Biomarker values were then compared between the severity cohorts and area under the curve (AUC), and cut-off values and performance characteristics were calculated.

Results:
A total of 108 patients met inclusion criteria with 46% having moderate/severe CAP. Elevated levels of CRP (51.7 mg/L in mild vs. 104.8 mg/L in moderate/severe, P = .003, PCT (0.29 ng/ml in mild vs. 4.02 ng/mL in moderate/severe, P = .001) and band counts (8% in mild vs. 15% moderate/severe, P = .009) were associated with increased pneumonia severity. In predicting moderate/severe CAP, PCT had the highest AUC of 0.77 (P = .001) followed by bands AUC of 0.69 (P = .009) and CRP AUC of 0.67 (P = .003). Cut-off for PCT of 0.55 ng/mL had a sensitivity of 83% and a specificity of 65%. Cut-off level of 53.1 mg/L for CRP had a sensitivity of 79% and specificity of 52%. Cut off level of 12.5% bands had a sensitivity of 61% and specificity of 71%. In a multivariable model controlled for patient demographics and other biomarker levels, only PCT levels significantly predicted moderate/severe CAP (adjusted odds ratio: 1.40 [95% CI, 1.14–1.73], P = .002).

Conclusion:
Biomarkers, in particular PCT, obtained early in hospitalization may perform as possible predictors for CAP severity in children and be beneficial in guiding CAP management. However, biomarkers in pneumonia should not drive severity assessment or patient management independent of clinical presentation.