bluuebunny/crossref_metadata_2025 huggingface dataset:
Two new species of Fistulina (Agaricales, Basidiomycota) from the Northern Hemisphere
Authors: Zhou Meng , Liu Zhan-Bo , Lim Young Woon , Cho Yoonhee , Yang Rui-Heng , Bao Da-Peng , Zhao Chang-Lin , Li De-Wei , Vlasák Josef , Dai Yu-Cheng
Published: December 2022

Phylogenetic and morphological analyses on samples of Fistulina from East Asia and North America were carried out, and two new species were described, namely, Fistulina americana and Fistulina orientalis, both previously known as Fistulina hepatica. The former is characterized by lateral stipitate basidiocarps, relatively small pores (7–8 per mm), a monomitic hyphal system with both clamp connections and simple septa, and ellipsoid basidiospores of 4–4.8 × 3–3.3 μm, and the species has been found on Quercus in North-East USA. F. orientalis is characterized by lateral stipitate basidiocarps, very small pores (11–12 per mm) with pruinose dissepiments, a monomitic hyphal system with both clamp connections and simple septa, and ovoid to subglobose basidiospores of 3–4 × 2.7–3 μm, and the species has been found on Castanopsis in East Asia. Phylogenetically, samples of F. americana and F. orientalis form two new lineages nested in the Fistulina clade.
Classification of dry and wet macular degeneration based on the ConvNeXT model
Authors: Wu Maonian , Lu Ying , Hong Xiangqian , Zhang Jie , Zheng Bo , Zhu Shaojun , Chen Naimei , Zhu Zhentao , Yang Weihua
Published: December 2022

Purpose

To assess the value of an automated classification model for dry and wet macular degeneration based on the ConvNeXT model.

Methods

A total of 672 fundus images of normal, dry, and wet macular degeneration were collected from the Affiliated Eye Hospital of Nanjing Medical University and the fundus images of dry macular degeneration were expanded. The ConvNeXT three-category model was trained on the original and expanded datasets, and compared to the results of the VGG16, ResNet18, ResNet50, EfficientNetB7, and RegNet three-category models. A total of 289 fundus images were used to test the models, and the classification results of the models on different datasets were compared. The main evaluation indicators were sensitivity, specificity, F1-score, area under the curve (AUC), accuracy, and kappa.

Results

Using 289 fundus images, three-category models trained on the original and expanded datasets were assessed. The ConvNeXT model trained on the expanded dataset was the most effective, with a diagnostic accuracy of 96.89%, kappa value of 94.99%, and high diagnostic consistency. The sensitivity, specificity, F1-score, and AUC values for normal fundus images were 100.00, 99.41, 99.59, and 99.80%, respectively. The sensitivity, specificity, F1-score, and AUC values for dry macular degeneration diagnosis were 87.50, 98.76, 90.32, and 97.10%, respectively. The sensitivity, specificity, F1-score, and AUC values for wet macular degeneration diagnosis were 97.52, 97.02, 96.72, and 99.10%, respectively.

Conclusion

The ConvNeXT-based category model for dry and wet macular degeneration automatically identified dry and wet macular degeneration, aiding rapid, and accurate clinical diagnosis.
Genetic etiological analysis of auditory neuropathy spectrum disorder by next-generation sequencing
Authors: Sun Lianhua , Lin Zhengyu , Zhang Jifang , Shen Jiali , Wang Xiaowen , Yang Jun
Published: December 2022

Objective

Auditory neuropathy spectrum disease (ANSD) is caused by both environmental and genetic causes and is defined by a failure in peripheral auditory neural transmission but normal outer hair cells function. To date, 13 genes identified as potentially causing ANSD have been documented. To study the etiology of ANSD, we collected 9 probands with ANSD diagnosed in the clinic and performed targeted next-generation sequencing.

Methods

Nine probands have been identified as ANSD based on the results of the ABR tests and DPOAE/CMs. Genomic DNA extracted from their peripheral blood was examined by next-generation sequencing (NGS) for a gene panel to identify any potential causal variations. For candidate pathogenic genes, we performed co-segregation among all family members of the pedigrees. Subsequently, using a mini-gene assay, we examined the function of a novel splice site mutant of OTOF.

Results

We analyzed nine cases of patients with ANSD with normal CMs/DPOAE and abnormal ABR, discovered three novel mutants of the OTOF gene that are known to cause ANSD, and six cases of other gene mutations including TBC1D24, LARS2, TIMM8A, MITF, and WFS1.

Conclusion

Our results extend the mutation spectrum of the OTOF gene and indicate that the genetic etiology of ANSD may be related to gene mutations of TBC1D24, LARS2, TIMM8A, MITF, and WFS1.
Misdiagnosis of Susac syndrome as demyelinating disease and primary angiitis of the central nervous system: A case report
Authors: Wu Gang , Jiang Wei , Li Zunbo , Huang Dehui , Wu Lei
Published: December 2022

Susac syndrome (SuS) is a rare neuroinflammatory disease that manifests with a triad of hearing loss, branch retinal artery occlusions, and encephalopathy. Patients with SuS are frequently misdiagnosed because the clinical trial is incompletely present at disease onset. In this report, we present a case of a 29-year-old man manifesting sleepiness, epilepsy, urinary dysfunction, and hemiparesis at the initial stage. Magnetic resonance imaging (MRI) revealed multiple abnormal signals located in the lateral paraventricular, corpus callosal, and pons. In addition, the patient had sustained elevation of CSF pressure and protein. ADEM was considered according to the clinical and radiographic findings. However, symptoms were not significantly improved after methylprednisolone therapy. He showed a vision decline in the third month after the disease onset. It was considered from intracranial hypertension or optic neuritis, and therefore retinal arteriolar impairment was ignored. As the disease progresses, cognitive decline was presented. Brain MRI exhibits multiple significant hyperintensities on the DWI sequence with speck-like gadolinium enhancement. Thus, PACNS was diagnosed. The SuS was not made until the presence of hearing decline in the 4 months after the disease onset. The case will be helpful for clinicians to better recognize the atypical initial manifestation of SuS.
Case Report: Transvertebral transposition of the spinal cord for recovery after paraplegia during kyphoscoliosis surgery
Authors: Chen Chao , Zhao Zhen , Li Jing , Xu Qiankun , Zhong Weibin , Wang Bingjin , Zhu Lingwei , Yang Cao , Gao Yong
Published: December 2022

Introduction

Neurological impairment during spinal deformity surgery is the most serious possible complication. When confronting intraoperative neurophysiological monitoring alerts, various surgical management methods such as the release of implants and decompression of the spinal cord are always performed. Transvertebral transposition of the spinal cord is rarely performed, and its role in the management of acute paraplegia is seldom reported.

Case description

The authors present two patients with kyphoscoliosis who experienced neurological deficits and abnormal neurological monitoring intraoperatively or post-operatively that were detected during correction surgery. Acute paraplegia was confirmed by a wake-up test. Subsequent spinal cord transposition was performed. Intraoperative neurophysiological monitoring motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SEPs) were performed to detect the changes during the process. After transvertebral transposition of the spinal cord, the MEPs and SEPs were significantly improved in both patients during surgery. The spinal cord function was restored post-operatively and recovered to normal at the final follow-up in two patients.

Conclusion

This case demonstrated that instead of decreasing the correction ratio of kyphoscoliosis, transvertebral transposition of the spinal cord under intraoperative neurophysiological monitoring may be an alternative therapeutic strategy for acute spinal cord dysfunction caused by deformity correction surgeries.
Therapeutic approaches for improving cognitive function in the aging brain
Authors: Chen Lingmin , Jiao Jiao , Zhang Yonggang
Published: December 2022

The rapid aging of populations around the world has become an unprecedented challenge. Aging is associated with cognitive impairment, including dementia and mild cognitive impairment. Successful drug development for improving or maintaining cognition in the elderly is critically important. Although 4 drugs for improving cognition in Alzheimer’s disease have been approved, a variety of potential drugs targeting age-related cognitive impairment are still in development. In addition, non-pharmacological interventions, including cognition-oriented treatments, non-invasive brain stimulation physical exercise, and lifestyle-related interventions, have also been suggested as cognitive enhancers in the last decade. In this paper, we reviewed the recent evidence of pharmacological and non-pharmacological interventions aimed at improving or maintaining cognition in the elderly.
A nutritional supplement based on a synbiotic combination of Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine improves glucose metabolism in healthy prediabetic subjects – A real-life post-marketing study
Authors: Kordowski Anna , Tetzlaff-Lelleck Vivian Valeska , Speckmann Bodo , Loh Gunnar , Künstner Axel , Schulz Franziska , Schröder Torsten , Smollich Martin , Sina Christian , tom Dieck Heike
Published: December 2022

Introduction

Impaired glucose homeostasis is a significant risk factor for cardiometabolic diseases, whereas the efficacy of available standard therapies is limited, mainly because of poor adherence. This post-marketing study assessed the glucose-lowering potential of a synbiotic-based formulation.

Methods

One hundred ninety-two participants were enrolled in a digital nutrition program with continuous glucose monitoring (CGM) and received a study product comprising Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine. Participants underwent a first sensor phase without supplementation, followed by a 14-day supplementation phase without sensor, and completed by a second sensor phase while continuing supplementation. Fasting glucose levels were determined before and after supplementation by CGM. In addition, the postprandial glycemic response to an oral glucose challenge, body weight, HbA1c concentrations, and BMI was analyzed. Subgroup analyses of subjects with elevated glucose and HbA1c levels vs. normoglycemic subjects were performed.

Results

Supplementation with the study product resulted in significant improvements in glucose parameters (delta values: fasting glucose –2,13% ± 8.86; iAUC0–120 –4.91% ± 78.87; HbA1c: –1.20% ± 4.72) accompanied by a significant weight reduction (−1.07 kg ± 2.30) in the study population. Subgroup analyses revealed that the improvements were mainly attributed to a prediabetic subgroup with elevated fasting glucose and HbA1c values before supplementation (delta values: fasting glucose −6.10% 4± 7.89; iAUC0–120 –6.28% ± 115.85; HbA1c −3.31% ± 4.36; weight: −1.47 kg ± 2.82).

Conclusion

This study indicates that the synbiotic composition is an effective and convenient approach to counteract hyperglycemia. Further placebo-controlled studies are warranted to test its efficacy in the treatment of cardiometabolic diseases.
Poor adherence to iron-folic acid supplementation and associated factors among pregnant women who had at least four antenatal care in Ethiopia. A community-based cross-sectional study
Authors: Asmamaw Desale Bihonegn , Debebe Negash Wubshet , Bitew Desalegn Anmut , Belachew Tadele Biresaw
Published: December 2022

Background

In developing countries, including Ethiopia, maternal mortality is a major public health concern. The Ethiopian Demographic Health Survey (EDHS) reported that the maternal mortality ratio (MMR) was 420 per 100,000 live births in 2016. Iron-folic acid supplementation (IFAS) is a key intervention to reduce these deaths. Therefore, this study aimed to assess the magnitude of poor adherence to IFAS and associated factors among pregnant women who had at least four antenatal care in Ethiopia.

Methods

Secondary data analysis was used using 2016 Ethiopian Demographic and Health Survey (EDHS). We analyzed the data using Stata version 14. To identify factors associated with poor adherence to IFAS, a multilevel mixed-effect logistic regression model was fitted. Variables with a p < 0.05 in the multilevel mixed-effect logistic regression model were declared as significant factors associated with poor adherence to IFAS.

Result

The magnitude of poor adherence to IFAS was 82.87% (95% CI: 80.96–84.65). Women education; primary [adjusted odds ratio (AOR) = 0.48; 95% CI: 0.31–0.75] and secondary (AOR = 0.52; 95% CI: 0.29–0.96), husband education; primary (AOR = 0.56; 95% CI: 0.36–0.86) and secondary (AOR = 0.51; 95% CI: 0.29–0.95), and community media exposure (AOR = 0.47; 95% CI: 0.27–0.79) were significantly associated with poor adherence to IFAS.

Conclusion

In the current study, more than eight out of ten pregnant women who had at least four antenatal care had poor adherence to IFAS. Thus, promoting maternal and husband education and establishing community media with a priority on iron-folic acid supplementation and health-related programs are essential strategies to reduce poor adherence to IFAS.
Educational inequality in consumption of in natura or minimally processed foods and ultra-processed foods: The intersection between sex and race/skin color in Brazil
Authors: Crepaldi Barbara Virginia Caixeta , Okada Letícia Martins , Claro Rafael Moreira , Louzada Maria Laura da Costa , Rezende Leandro F. M. , Levy Renata Bertazzi , Azeredo Catarina Machado
Published: December 2022

Background

It remains uncertain how the intersection between educational, gender, and race/skin color inequalities influences food consumption in Brazil. In this study, we examined the educational inequality in the consumption of in natura/minimally processed and ultra-processed foods by Brazilians with an intersectional perspective between sex and race/color.

Methods

We used cross-sectional data from the Telephone Surveillance System (VIGITEL 2019), comprising 52,443 participants ≥ 18 years. Daily food consumption was considered high when consumption of ≥5 foods for each food group was reported the day before the survey. Educational inequality in food consumption was assessed by the slope index of inequality (SII) and the relative index of inequality (RII) according to sex and race/color (White; Black/Brown). Positive SII and RII values > 1.0 indicate higher food consumption among more educated participants.

Results

The consumptions of in natura/minimally processed and ultra-processed foods were more prevalent in those with the highest level of education (≥12 years) and intermediate education (9–11 years), respectively. However, highly educated White women had higher consumption of in natura/minimally processed foods than Black women with the same education level, and White men in low and intermediate school levels had higher consumption of these foods than Black men with the same education levels. We found higher absolute educational inequality for in natura/minimally processed foods among White women (SII 21.8, 95% CI 15.3, 28.4) and Black/Brown men (SII 19.3, 95% CI 12.5, 26.1). Black/Brown men (SII 7.3, 95% CI 0.5, 14.0) and Black/Brown women (SII 5.6, 95% CI 1.0, 10.2) had higher absolute educational inequality than White men (SII −3.3, 95% CI −10.9, 4.3; P = 0.04) in the consumption of ultra-processed foods.

Conclusion

Educational inequalities influenced the consumption of in natura/minimally processed more than ultra-processed foods, and, for the latter, inequalities were greater among Black/Brown men and women than among White men.
Association between nut consumption and mortality among Chinese older people: A national cohort study based on CLHLS from 2008 to 2018
Authors: He Dengxin , Huangfu Zheng , Pan Minghao
Published: December 2022

Background

Few quantitative studies have explored the associations between nut consumption and better health outcomes among a national cohort of community-dwelling older Chinese people. Given the need for more evidence to support the health benefits of nuts among Chinese people, we investigated whether nut consumption was associated with subsequent 10-year mortality.

Methods

We analyzed data from the Chinese Longitudinal Healthy Longevity Survey. The data on nut consumption at baseline were collected using a questionnaire through face-to-face interviews. The vital status and date of death were ascertained by a close family member or village doctor of the deceased participant during the follow-up survey. Cox analyses were performed to explore the association between nut consumption and mortality. Subgroup analyses by age group (<80 or ≥80 years), sex (male/female), activities of daily living (impaired or normal), and physical exercise (yes or no) were performed to assess whether the association between nut consumption and mortality differed across different populations.

Results

The median survival time was 1,302 days for the 11,915 participants with complete information of survival time and nut consumption. The association between nut consumption and mortality was significant after the adjusting for significant factors in the univariate Cox analyses. The hazard ratios were lower in male participants, those who were <80 years old, and those who did not engage in physical exercise at baseline. The association between nut consumption and mortality was not significant among participants with normal activities of daily living.

Conclusion

The association between nut consumption and mortality was not significant among participants who had normal activities of daily living but was significant among participants who had impaired activities of daily living. Including nuts in the diets cloud help to extend the lifespan in older Chinese people, especially those with impaired activities of daily living.
The association between personal social capital and health-related quality of life among Chinese older people: A cross-sectional study
Authors: Jiang Dongdong , Yan Yajie , Zhou Han , Wang Quan
Published: December 2022

Background

Lower health-related quality of life (HRQoL) can result in adverse effects on the health of older people. This study aims to explore the relationship between personal social capital (PSC) and HRQoL among Chinese elderly people from rural-and-urban perspective.

Materials and methods

4,802 samples were included from China’s health-related quality of life Survey for Older Adults 2018 (CHRQLS-OA 2018). The PSC, including bonding and bridging social capital (BOC and BRC), was measured by the Chinese version of the Personal Social Capital Scale (PSCS-16). The HRQoL was evaluated by the European Five Dimensions Questionnaire (EQ-5D-3L). Linear and Tobit regression models were conducted to examine the relationship between PSC and HRQoL.

Results

The BOC and BRC of rural older people were significantly lower than those of urban older people. Pain/discomfort and anxiety/depression were the most significant health problems affecting the older samples. In the five dimensions, the proportion of rural older people with problems was higher than that of urban older people. Among rural older people, BOC was significantly related to self-rated health and EQ-5D utility index (p < 0.05); while BRC was insignificantly associated with self-rated health (p > 0.05) but related to EQ-5D utility index (p < 0.05). Both BOC and BRC were significantly correlated with self-rated health and EQ-5D utility index (p < 0.05) among urban older people.

Conclusion

Our study reveals older people’s worrying PSC and HRQoL status. The relationship between PSC and HRQoL suggested that more social support and care of intimates should be encouraged to increase the PSC of older people, especially rural older people.
Impact of the time of surgical delay on survival in patients with muscle-invasive bladder cancer
Authors: Li Shuaishuai , Chen Rui , Raj Ashok , Xue Ning , Zhao Fangzheng , Shen Xihao , Peng Yunpeng , Zhu Haitao
Published: December 2022

Background and objectives

Patients with muscle-invasive bladder cancer (MIBC) often experience a waiting period before radical surgery for numerous reasons; however, the COVID-19 outbreak has exacerbated this problem. Therefore, it is necessary to discuss the impact of the unavoidable time of surgical delay on the outcome of patients with MIBC.

Methods

In all, 165 patients from high-volume centers with pT2-pT3 MIBC, who underwent radical surgery between January 2008 and November 2020, were retrospectively evaluated. Patients’ demographic and pathological information was recorded. Based on the time of surgical delay endured, patients were divided into three groups: long waiting time (> 90 days), intermediate waiting time (30–90 days), and short waiting time (≤ 30 days). Finally, each group’s pathological characteristics and survival rates were compared.

Results

The median time of surgical delay for all patients was 33 days (interquartile range, IQR: 16–67 days). Among the 165 patients, 32 (19.4%) were classified into the long waiting time group, 55 (33.3%) into the intermediate waiting time group, and 78 (47.3%) into the short waiting time group. The median follow-up period for all patients was 48 months (IQR: 23–84 months). The median times of surgical delay in the long, intermediate, and short waiting time groups were 188 days (IQR: 98–367 days), 39 days (IQR: 35–65 days), and 16 days (IQR: 12–22 days), respectively. The 5-year overall survival (OS) rate for all patients was 58.4%, and that in the long, intermediate, and short waiting time groups were 35.7%, 61.3%, and 64.1%, respectively (P = 0.035). The 5-year cancer-specific survival (CSS) rates in the long, intermediate, and short waiting time groups were 38.9%, 61.5%, and 65.0%, respectively (P = 0.042). The multivariate Cox regression analysis identified age, time of surgical delay, pT stage, and lymph node involvement as independent determinants of OS and CSS.

Conclusion

In patients with pT2-pT3 MIBC, the time of surgical delay > 90 days can have a negative impact on survival.
Enhancing diagnosis of T-cell lymphoma using non-recombined T-cell receptor sequences
Authors: Chen Yi-Lin , Ho Chung-Liang , Hung Chen-Yan , Chen Wan-Li , Chang Chen , Hou Yi-Hsin , Chen Jian-Rong , Chen Pin-Jun , Chow Nan-Haw , Huang Wenya , Hsu Ya-Ting , Chen Tsai-Yun , Liu Tsunglin
Published: December 2022

Clonality assessment, which can detect neoplastic T cells by identifying the uniquely recombined T-cell receptor (TCR) genes, provides important support in the diagnosis of T-cell lymphoma (TCL). BIOMED-2 is the gold standard clonality assay and has proven to be effective in European TCL patients. However, we failed to prove its sensitivity in Taiwanese TCL patients, especially based on the TCRβ gene. To explore potential impact of genetic background in the BIOMED-2 test, we analyzed TCRβ sequences of 21 healthy individuals and two TCL patients. This analysis suggests that genetic variations in the BIOMED-2 primer sites could not explain the difference in sensitivity. The BIOMED-2 test results of the two TCL patients were positive and negative, respectively. Interestingly, a higher percentage (>81%) of non-recombined TCRβ sequences was observed in the test-negative patient than those of the test-positive patient and all healthy individuals (13~66%). The result suggests a new TCR target for enhancing TCL diagnosis. To further explore the hypothesis, we proposed a cost-effective digital PCR assay that quantifies the relative abundance of non-recombined TCRβ sequences containing a J2-2P~J2-3 segment. With the digital PCR assay, bone marrow specimens from TCL patients (n=9) showed a positive outcome (i.e., the relative abundance of the J2-2P~J2-3 sequences ≧5%), whereas non-TCL patients (n=6) gave a negative result. As five of nine TCL patients had a negative BIOMED-2 test result, the J2-2P~J2-3 sequences may improve TCL detection. This is the first report showing the capability of characterizing non-recombined TCR sequences as a supplementary strategy for the BIOMED-2 clonality test.
Therapeutic drug monitoring for cytotoxic anticancer drugs: Principles and evidence-based practices
Authors: Smita Pattanaik , Narayan Patil Amol , J Kumaravel , Gaurav Prakash
Published: December 2022

Cytotoxic drugs are highly efficacious and also have low therapeutic index. A great degree of caution needs to be exercised in their usage. To optimize the efficacy these drugs need to be given at maximum tolerated dose which leads to significant amount of toxicity to the patient. The fine balance between efficacy and safety is the key to the success of cytotoxic chemotherapeutics. However, it is possibly more rewarding to obtain that balance for this class drugs as the frequency of drug related toxicities are higher compared to the other therapeutic class and are potentially life threatening and may cause prolonged morbidity. Significant efforts have been invested in last three to four decades in therapeutic drug monitoring (TDM) research to understand the relationship between the drug concentration and the response achieved for therapeutic efficacy as well as drug toxicity for cytotoxic drugs. TDM evolved over this period and the evidence gathered favored its routine use for certain drugs. Since, TDM is an expensive endeavor both from economic and logistic point of view, to justify its use it is necessary to demonstrate that the implementation leads to perceivable improvement in the patient outcomes. It is indeed challenging to prove the utility of TDM in randomized controlled trials and at times may be nearly impossible to generate such data in view of the obvious findings and concern of compromising patient safety. Therefore, good quality data from well-designed observational study do add immense value to the scientific knowledge base, when they are examined in totality, despite the heterogeneity amongst them. This article compiles the summary of the evidence and the best practices for TDM for the three cytotoxic drug, busulfan, 5-FU and methotrexate. Traditional use of TDM or drug concentration data for dose modification has been witnessing a sea change and model informed precision dosing is the future of cytotoxic drug therapeutic management.
Systematic literature review and meta-analysis of clinical outcomes and prognostic factors for melanoma brain metastases
Authors: Tan Xiang-Lin , Le Amy , Scherrer Emilie , Tang Huilin , Kiehl Nick , Han Jiali , Jiang Ruixuan , Diede Scott J. , Shui Irene M.
Published: December 2022

Background

More than 60% of all stage IV melanoma patients develop brain metastases, while melanoma brain metastases (MBM) is historically difficult to treat with poor prognosis.

Objectives

To summarize clinical outcomes and prognostic factors in MBM patients.

Methods

A systematic review with meta-analysis was conducted, and a literature search for relevant studies was performed on November 1, 2020. Weighted average of median overall survival (OS) was calculated by treatments. The random-effects model in conducting meta-analyses was applied.

Results

A total of 41 observational studies and 12 clinical trials with our clinical outcomes of interest, and 31 observational studies addressing prognostic factors were selected. The most common treatments for MBM were immunotherapy (IO), MAP kinase inhibitor (MAPKi), stereotactic radiosurgery (SRS), SRS+MAPKi, and SRS+IO, with median OS from treatment start of 7.2, 8.6, 7.3, 7.3, and 14.1 months, respectively. Improved OS was observed for IO and SRS with the addition of IO and/or MAPKi, compared to no IO and SRS alone, respectively. Several prognostic factors were found to be significantly associated with OS in MBM.

Conclusion

This study summarizes pertinent information regarding clinical outcomes and the association between patient characteristics and MBM prognosis.
A review of the therapeutic role of the new third-generation TKI olverembatinib in chronic myeloid leukemia
Authors: Qian Honglan , Gang Dongxu , He Xiaoyu , Jiang Songfu
Published: December 2022

Several tyrosine kinase inhibitors (TKIs) have been developed as targeted therapies to inhibit the oncogenic activity of several tyrosine kinases in chronic myeloid leukemia (CML), acute lymphoid leukemia (ALL), gastrointestinal stromal tumor (GIST), and other diseases. TKIs have significantly improved the overall survival of these patients and changed the treatment strategy in the clinic. However, approximately 50% of patients develop resistance or intolerance to imatinib. For second-generation TKIs, approximately 30%–40% of patients need to change therapy by 5 years when they are used as first-line treatment. Clinical study analysis showed that the T315I mutation is highly associated with TKI resistance. Developing new drugs that target the T315I mutation will address the dilemma of treatment failure. Olverembatinib, as a third-generation TKI designed for the T315I mutation, is being researched in China. Preliminary clinical data show the safety and efficacy in treating CML patients harboring the T315I mutation or who are resistant to first- or second-line TKI treatment. Herein, we review the characteristics and clinical trials of olverembatinib. We also discuss its role in the management of CML patients.
Acetylcholine receptor binding antibody–associated myasthenia gravis, myocarditis, and rhabdomyolysis induced by tislelizumab in a patient with colon cancer: A case report and literature review
Authors: Wang Shengnan , Peng Danping , Zhu Hao , Min Wanwan , Xue Mengru , Wu Rui , Shao Yanqing , Pan Lin , Zhu Mingqin
Published: December 2022

Despite the intriguing therapeutic prospects offered by immune checkpoint inhibitors (ICIs), immune-related adverse events (irAEs) become an increasingly important safety issue. Herein, we report a patient with locally advanced colorectal cancer (LACRC) who received anti-programmed cell death protein 1 (PD-1) (tislelizumab) therapy, then developed weakness of the limbs and drooping eyelids. He experienced sequential irAEs including severe myasthenia gravis, myocarditis, and rhabdomyolysis. Although many irAEs caused by tislelizumab have been reported, the cooccurrence of severe myasthenia gravis, myocarditis, and rhabdomyolysis caused by tislelizumab has not been described. The patient responded well to methylprednisolone and intravenous immunoglobulin therapy. This case illustrates the severe toxicity caused by ICIs, highlighting the importance of early prevention, early diagnosis, and appropriate management of irAEs. Multidisciplinary discussions should be held to improve the prognosis of patients.
Changes in lung cancer-related serum tumor markers in patients with chronic kidney disease and determination of upper reference limit
Authors: Miao Qiang , Cai Bei , Niu Qian , Zhang Junlong
Published: December 2022

Aims

To investigate the changes in lung cancer-related serum tumor markers in patients with chronic kidney disease (CKD) and determine the upper reference limit for patients with different stages.

Methods

Included inpatients diagnosed with CKD who did not receive dialysis temporarily in our hospital from March to September 2020. Changes in serum CA125, HE4, CYFRA21-1, SCCA, NSE and ProGRP in CKD patients were analyzed. The non-parametric method was used to estimate the upper reference limit of the above indicators in patients with CKD stages 2-5.

Results

The serum levels of HE4, CYFRA21-1, SCCA, and ProGRP in the CKD group were significantly higher than those in the healthy control group; CA125 and NSE levels were not statistically different. The false positives of SCC, CYFRA21-1, ProGRP, and HE4 increased significantly with the CKD stage. Still, NSE and CA125 did not show a significant increasing trend. Both HE4 and ProGRP have independent upper reference limits from CKD2 to CKD5 stage, namely 220.8 pmol/l and 101.4 pg/ml in the CKD2 stage, 496.7 pmol/l and 168.63 pg/ml in CKD3 stage, 4592.4 pmol/l and 272.8 pmol/l for CKD4 stage, CKD5 stage was 4778.2 pmol/l and 491.6 pmol/l.

Conclusion

This study preliminarily determined the upper reference limits of Lung cancer-related tumor markers in patients with different CKD stages and provided laboratory support for the rational use and interpretation of Lung cancer-related tumor markers in special populations.
Characterization of proteins, mRNAs, and miRNAs of circulating extracellular vesicles from prostate cancer patients compared to healthy subjects
Authors: Chisholm Jolene , Haas-Neill Sandor , Margetts Peter , Al-Nedawi Khalid
Published: December 2022

Prostate cancer (PC) is the fifth leading cause of death in men globally. Measurement of the blood PSA level is still considered the gold-standard biomarker test for PC despite its high rate of delivering false positives and negatives that result in an inappropriate medical response, including overtreatment. We collected extracellular vesicles (EVs) from the blood plasma of PC patients with organ-confined, extracapsular-invading, and seminal vesicle–invading tumors and from healthy subjects. We examined the protein, mRNA, and miRNA content of these EVs using mass spectrometry (MS), a human PC PCR array, and a miScript miRNA PCR array, respectively. The proteomic analysis showed distinct groups of proteins that are differently expressed in each group of patients, as well as in healthy subjects. Samples from healthy subjects and each tumor type were used for both mRNA and miRNA arrays. The mRNA analysis showed distinct groups of mRNAs that were overexpressed in healthy or in one of the three tumor types but not in the EVs of the other groups. The miRNA analysis showed distinct groups of miRNAs as well. The fold of regulation in the expression of the identified mRNA and miRNA of each stage of the disease from healthy subjects showed that various mRNAs and miRNAs could discriminate the disease stage. Overall, our data suggest many molecular marker candidates for distinguishing between healthy subjects and PC patients using the cargo of circulating vesicles, as well as markers to discriminate between the different tumor types. Once verified, these markers might have a diagnostic value for PC.
Case Report: Endoscopic manifestations and clinical features of small intestinal lymphangioma—A report of two cases
Authors: Wang Limei , Feng Huang , Chen Bingxin , Luan Fujuan
Published: December 2022

Objective

The aims of this study were to analyze the clinical characteristics, auxiliary examinations, and treatment measures of small intestinal lymphangioma and to improve the clinical diagnostic ability of clinicians.

Methods

This paper reports two cases of small intestinal lymphangioma in the Department of Gastroenterology, the First Affiliated Hospital of Soochow University, and makes a comprehensive analysis.

Results

A 31-year-old woman went to the hospital with complaints of dizziness, fatigue, and anemia. A 52-year-old woman complained of upper abdominal pain and went to the hospital with abdominal pain awaiting investigation. Both patients were subjected to three major routine examinations, tumor complete set, CT, capsule endoscopy, and deep enteroscopy, and both of them underwent complete resection of the affected intestinal segment. Pathology showed that both patients had small intestinal lymphangioma.

Conclusions

The clinical manifestations of small intestinal lymphangioma lack specificity. Capsule endoscopy and deep enteroscopy are helpful for clinical diagnosis, and pathological examination is still the gold standard. Surgical treatment can achieve better results.
Case report: First report of haploidentical allogeneic hematopoietic stem cell transplantation from donors with mild alpha-thalassemia for acute leukemia
Authors: Zheng Wenshuai , Wu Yamei , Guan Lixun , Cheng Longcan , Hu Yalei , Tan Min , Yang Yuhui , Ning Hongmei
Published: December 2022

For acute leukemia (AL) with adverse prognostic factors, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the standard care option after the first complete remission. Meanwhile, as the success of haploidentical HSCT (haplo-HSCT), haploidentical donors (HIDs) become a reliable choice. However, there have been no reports on haplo-HSCT from HIDs with mild alpha(α)-thalassemia for AL yet. In the present report, we first describe two cases of successful haplo-HSCT from HIDs with mild α-thalassemia for AL.
Trends of sphincter-preserving surgeries for low lying rectal cancer: A 20-year experience in China
Authors: Zheng Kuo , Hu Qingqing , Yu Guanyu , Zhou Leqi , Yao Yuting , Zhou Yuan , Wang Hao , Hao Liqiang , Yu Enda , Lou Zheng , Zhang Yongjing , Qiu Hong , Meng Ronggui , Zhang Wei
Published: December 2022

Background

Over the last 2 decades, patients with low rectal cancer have had better outcomes from improvements in surgical techniques in sphincter preservation. We aimed to quantify the trends in sphincter-preserving surgeries for low rectal cancer over 20 years in a top tertiary hospital in China.

Methods

Between 1999 and 2021, a cohort of patients with primary malignant rectal tumor ≤5cm from the anal verge and who received elective surgeries at Changhai Hospital, Shanghai, China, was identified. Data were extracted from electronic medical records. A Joinpoint Regression Model was used to analyze trends in surgical procedures by average annual percentage change (AAPC). Adjusted Cox proportional hazards regression model was used to assess overall survival.

Results

Among a total of 4,172 patients during the study period, 3,111 (74.6%) underwent a sphincter-preserving surgery and 1,061 (25.4%) received APR. Sphincter-preserving surgery increased 3.6% per year (95%CI, 2.3-4.9). Low anterior resection was the most performed procedure (86.3%) and maintained a steady trend, while intersphincteric resection increased 49.4% annually (95%CI, 19.5-86.7) after initiation. Laparoscopic techniques increased 15.1% per year (95%CI, 8.4-43.4) after initiation. Sphincter-preserving surgery increased annually for tumors ≤2cm, 2-≤3cm and 3-≤4cm from the anal verge (AAPC 7.1, 4.5-9.8; 4.7, 3.1-6.3; 2.7, 1.7-3.6, respectively). Furthermore, patients with sphincter-preserving surgery had a better overall survival than abdominoperineal resection (APR) patients (adjusted HR 0.78, 95% CI, 0.65-0.93, p=.01).

Conclusions

Utilization of sphincter-preserving surgeries increased significantly over the last 20 years. Patients with low rectal cancer who underwent sphincter preservation had better survival than similar patients who underwent APR.
Clinical diagnosis and treatment of subungual exostosis in children
Authors: Li Hao , Li Haichong , Qi Xinyu , Guo Dong , Cao Jun , Bai Yunsong , Yao Ziming , Zhang Xuejun
Published: December 2022

Objective

To analyze and summarize the clinical characteristics and treatment effects for subungual exostosis in children.

Methods

Clinical data for children with subungual exostosis treated in our department from January 2008 to September 2022 were evaluated.

Results

Forty children with subungual exostosis were evaluated, comprising 31 boys (77.5%) and 9 girls (22.5%) with a median age of 9 years (4–17 years). The median disease course was 6 months (1–48 months). Seven patients (17.5%) had definite trauma history and 5 (12.5%) had infection. The toe or finger nail appearance was abnormal in 36 patients and normal in 4 patients. Twenty-seven patients (67.5%) had pain when wearing shoes and walking, and 25 (62.5%) had toenail tenderness. The lesions were located in the distal phalanxes of the toes in 37 patients (92.5%), with 14 patients affected on the left side and 23 on the right side. Twenty-two patients had lesions in the great toe, 6 in the second toe, 6 in the third toe, and 3 in the fourth toe. The lesions in the other 3 patients (7.5%) were located in the distal phalanxes of the fingers, with 2 patients affected in the second finger and 1 in the third finger. Regarding the relationship between lesion location and nail bed, 4 patients were type I, 21 were type II, and 15 were type III. All 40 patients received surgical treatment, with nail removal in 15. The median maximum lesion diameter was 1.0 cm (0.8–2 cm), median operation time was 25 min (20–45 min), median blood loss was 1 ml (1–2 ml), and median postoperative hospital stay was 2 days (1–4 days). All cases were histopathologically confirmed as subungual exostosis. The median follow-up time was 24 months (3–60 months), with normal appearance of the toe or finger nail. There were no complications in 38 patients (95.0%). Two patients (5.0%) relapsed at 3 months postoperatively and underwent a secondary operation, with no subsequent recurrence during 12 months of follow-up.

Conclusion

Subungual exostosis in children is a rare benign disease that often occurs in the toes. Selection of the appropriate incision and nail bed treatment based on the relationship between lesion location and nail bed is helpful for improving the treatment effect.
Efficacy and safety of tirzepatide in patients with type 2 diabetes: A systematic review and meta-analysis
Authors: Tang Yan , Zhang Lin , Zeng Yuping , Wang Xia , Zhang Mei
Published: December 2022

Purpose: A systematic review and meta-analysis was conducted to combine the data available from clinical trials and evaluate the clinical efficacy and safety of tirzepatide in people with type 2 diabetes (T2D).

Methods: We systematically searched the MEDLINE, Embase, Cochrane Library, and clinical trials registries (https://clinicaltrials.gov) up to 25 March 2022 for randomized controlled trials (RCTs) that compared tirzepatide with placebo or active hypoglycemic drugs in subjects with T2D. Heterogeneity was judged by the I2 value and Cochran’s Q test. The randomized effects model was adopted to calculate risk ratios and weighted mean differences (WMDs). The primary outcome was the change from baseline in HbA1c levels. Secondary efficacy endpoints were fasting serum glucose (FSG), change of body weight, blood pressure, fasting lipid profiles, and safety indexes.

Results: Six trials comprising 6,579 subjects (4,410 in the tirzepatide group and 2,054 in the control group) fulfilled the pre-specified criteria and were included in the study. Tirzepatide treatment resulted in reducing HbA1c (WMD: -1.07%; 95% confidence intervals [CIs]: −1.44, −0.56), FSG (WMD, −21.50 mg/dl; 95% CI: −34.44, −8.56), body weight (WMD: −7.99 kg; 95% CI −11.36, −4.62), and blood pressure and ameliorated fasting lipid profiles, without increasing hypoglycemia, either as monotherapy or an add-on therapy. Tirzepatide increased the risk of gastrointestinal adverse events mainly in add-on therapy but not in terms of pancreatitis or cholelithiasis. Furthermore, tirzepatide presented a dose–response effect on the reduction in HbA1c and body weight and increase in nausea and vomiting.

Conclusion: In patients with type 2 diabetes, tirzepatide shows superior blood glucose control and weight loss performance, without an increased risk of hypoglycemia.

Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO), identifier (CRD42022319442).
Comprehensive assessment on the applications of oncolytic viruses for cancer immunotherapy
Authors: Omole Richard Kolade , Oluwatola Oluwaseyi , Akere Millicent Tambari , Eniafe Joseph , Agboluaje Elizabeth Oladoyin , Daramola Oluwafemi Bamidele , Ayantunji Yemisi Juliet , Omotade Temiloluwa Ifeoluwa , Torimiro Nkem , Ayilara Modupe Stella , Adeyemi Oluwole Isaac , Salinsile Olubusola Sajanat
Published: December 2022

The worldwide burden of cancers is increasing at a very high rate, including the aggressive and resistant forms of cancers. Certain levels of breakthrough have been achieved with the conventional treatment methods being used to treat different forms of cancers, but with some limitations. These limitations include hazardous side effects, destruction of non-tumor healthy cells that are rapidly dividing and developing, tumor resistance to anti-cancer drugs, damage to tissues and organs, and so on. However, oncolytic viruses have emerged as a worthwhile immunotherapeutic option for the treatment of different types of cancers. In this treatment approach, oncolytic viruses are being modeled to target cancer cells with optimum cytotoxicity and spare normal cells with optimal safety, without the oncolytic viruses themselves being killed by the host immune defense system. Oncolytic viral infection of the cancer cells are also being genetically manipulated (either by removal or addition of certain genes into the oncolytic virus genome) to make the tumor more visible and available for attack by the host immune cells. Hence, different variants of these viruses are being developed to optimize their antitumor effects. In this review, we examined how grave the burden of cancer is on a global level, particularly in sub-Saharan Africa, major conventional therapeutic approaches to the treatment of cancer and their individual drawbacks. We discussed the mechanisms of action employed by these oncolytic viruses and different viruses that have found their relevance in the fight against various forms of cancers. Some pre-clinical and clinical trials that involve oncolytic viruses in cancer management were reported. This review also examined the toxicity and safety concerns surrounding the adoption of oncolytic viro-immunotherapy for the treatment of cancers and the likely future directions for researchers and general audience who wants updated information.
Calcified plaque detected on OCT with deep learning and cross-validated with optical and ultrasound signals: A complementary appraisal and preamble to combined IVUS-OCT catheter
Authors: Huang Jiayue , Ninomiya Kai , Tu Shengxian , Masuda Shinichiro , Dijkstra Jouke , Chu Miao , Ding Daixin , Hynes Sean O. , O’Leary Neil , Wijns William , Onuma Yoshinobu , Serruys Patrick W.
Published: December 2022

Background: The optical coherence tomography (OCT)-deep learning (DL) emerged as a promising tool for automated plaque characterization. However, its findings have not been compared with optical and ultrasound signals.

Objectives: The objective was to cross-validate the calcified plaque detected by OCT-DL, using comprehensive tissue characterization technologies including OCT-derived optical properties, intravascular ultrasound (IVUS)-virtual histology (VH) and echogenicity.

Methods: Five years after bioresorbable scaffold (BRS) implantation, 15 patients underwent OCT and IVUS imaging. The unique platinum markers in BRS facilitated precise OCT-IVUS co-registration. Calcified plaque detected by OCT-DL were corroborated by/with optical properties, greyscale (GS)-IVUS, IVUS-VH and echogenicity. The concordance between OCT-DL and other modalities was assessed by kappa statistics. The calcium arc measured by different modalities were compared by orthogonal linear regression.

Results: Forty-three calcified plaques were detected by DL in 72 matched anatomic slices, 41 (95%) were confirmed as pure (n = 29) or hybrid calcified plaque (n = 12) by optical properties. Weighted kappa between OCT-DL and GS-IVUS, IVUS-VH and echogenicity were 0.69, 0.60 and 0.60, respectively. After having excluded artifactual optical shadowing (n = 5) generated by guidewire or platinum marker, kappa increased to 0.77, 0.68 and 0.69, with agreement ranging between 90% and 93%. Calcium arc derived from OCT-DL showed moderate correlation and agreement with GS-IVUS (ICCa = 0.81, difference = 1.73 ± 15.25°), IVUS-VH (ICCa = 0.69, difference = -5.60 ± 21.19°) and echogenicity (ICCa = 0.65, difference = 10.28 ± 18.70°).

Conclusion: OCT empowered by deep learning showed substantial agreement with optical and ultrasound signals. The comprehensive assessment provided by OCT and IVUS heralds the potential diagnostic value of combined IVUS-OCT catheters.