bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin resistance is associated with an unfavorable outcome among non-diabetic patients with isolated moderate-to-severe traumatic brain injury – A propensity score-matched study
Authors: Cao Cheng , Wang Huxu , Gao Heng , Wu Wei
Published: July 2022

Background

Hyperglycemia is an independent risk factor for the poor prognosis in patients with traumatic brain injury (TBI), and stress-induced impaired insulin function is the major factor of hyperglycemia in non-diabetic patients with TBI. Several types of research suggested that insulin resistance (IR) is related to the poor prognosis of neurocritical ill patients; here we focused on the role of IR in non-diabetic patients after TBI.

Methods

We performed a prospective observational study with the approval of the Ethics Committee of our institute. IR was accessed via the update Homeostasis Model Assessment (HOMA2) of IR, a computer-calculated index by glucose and insulin level. HOMA2 ≥ 1.4 was considered as the threshold of IR according to the previous studies. The glycemic variability (GV) indices were calculated by fingertip blood glucose concentration at an interval of 2 h within 24 h to explore the relationship between IR and GV. The outcome was the 6-month neurological outcome evaluated with the Glasgow outcome scale.

Results

A total of 85 patients with isolated moderate-to-severe TBI (admission GCS ≤ 12) were finally included in our study, 34 (40%) were diagnosed with IR with HOMA2 ≥ 1.4. After propensity score matching (PSM), 22 patients in IR group were matched to 34 patients in non-IR group. Patients with IR suffered increased systemic glycemic variation after isolated moderate-to-severe TBI. IR was a significant factor for the poor prognosis after TBI (OR = 3.25, 95% CI 1.03–10.31, p = 0.041).

Conclusions

The IR estimated by HOMA2 was associated with greater GV and an unfavorable outcome after isolated moderate-to-severe TBI. Ameliorating impaired insulin sensitivity may be a potential therapeutic strategy for the management of TBI patients.
Hypersensitivity to passive voice hearing in hallucination proneness
Authors: Johnson Joseph F. , Belyk Michel , Schwartze Michael , Pinheiro Ana P. , Kotz Sonja A.
Published: July 2022

Voices are a complex and rich acoustic signal processed in an extensive cortical brain network. Specialized regions within this network support voice perception and production and may be differentially affected in pathological voice processing. For example, the experience of hallucinating voices has been linked to hyperactivity in temporal and extra-temporal voice areas, possibly extending into regions associated with vocalization. Predominant self-monitoring hypotheses ascribe a primary role of voice production regions to auditory verbal hallucinations (AVH). Alternative postulations view a generalized perceptual salience bias as causal to AVH. These theories are not mutually exclusive as both ascribe the emergence and phenomenology of AVH to unbalanced top-down and bottom-up signal processing. The focus of the current study was to investigate the neurocognitive mechanisms underlying predisposition brain states for emergent hallucinations, detached from the effects of inner speech. Using the temporal voice area (TVA) localizer task, we explored putative hypersalient responses to passively presented sounds in relation to hallucination proneness (HP). Furthermore, to avoid confounds commonly found in in clinical samples, we employed the Launay-Slade Hallucination Scale (LSHS) for the quantification of HP levels in healthy people across an experiential continuum spanning the general population. We report increased activation in the right posterior superior temporal gyrus (pSTG) during the perception of voice features that positively correlates with increased HP scores. In line with prior results, we propose that this right-lateralized pSTG activation might indicate early hypersensitivity to acoustic features coding speaker identity that extends beyond own voice production to perception in healthy participants prone to experience AVH.
Type of bilingualism conditions individual differences in the oscillatory dynamics of inhibitory control
Authors: Pereira Soares Sergio Miguel , Prystauka Yanina , DeLuca Vincent , Rothman Jason
Published: July 2022

The present study uses EEG time-frequency representations (TFRs) with a Flanker task to investigate if and how individual differences in bilingual language experience modulate neurocognitive outcomes (oscillatory dynamics) in two bilingual group types: late bilinguals (L2 learners) and early bilinguals (heritage speakers—HSs). TFRs were computed for both incongruent and congruent trials. The difference between the two (Flanker effect vis-à-vis cognitive interference) was then (1) compared between the HSs and the L2 learners, (2) modeled as a function of individual differences with bilingual experience within each group separately and (3) probed for its potential (a)symmetry between brain and behavioral data. We found no differences at the behavioral and neural levels for the between-groups comparisons. However, oscillatory dynamics (mainly theta increase and alpha suppression) of inhibition and cognitive control were found to be modulated by individual differences in bilingual language experience, albeit distinctly within each bilingual group. While the results indicate adaptations toward differential brain recruitment in line with bilingual language experience variation overall, this does not manifest uniformly. Rather, earlier versus later onset to bilingualism—the bilingual type—seems to constitute an independent qualifier to how individual differences play out.
Preliminary psychometric properties of a standard vocabulary test administered using a non-invasive brain-computer interface
Authors: Warschausky Seth , Huggins Jane E. , Alcaide-Aguirre Ramses Eduardo , Aref Abdulrahman W.
Published: July 2022

Objective

To examine measurement agreement between a vocabulary test that is administered in the standardized manner and a version that is administered with a brain-computer interface (BCI).

Method

The sample was comprised of 21 participants, ages 9–27, mean age 16.7 (5.4) years, 61.9% male, including 10 with congenital spastic cerebral palsy (CP), and 11 comparison peers. Participants completed both standard and BCI-facilitated alternate versions of the Peabody Picture Vocabulary Test - 4 (PPVT™-4). The BCI-facilitated PPVT-4 uses items identical to the unmodified PPVT-4, but each quadrant forced-choice item is presented on a computer screen for use with the BCI.

Results

Measurement agreement between instruments was excellent, including an intra-class correlation coefficient of 0.98, and Bland-Altman plots and tests indicating adequate limits of agreement and no systematic test version bias. The mean standard score difference between test versions was 2.0 points (SD 6.3).

Conclusion

These results demonstrate that BCI-facilitated quadrant forced-choice vocabulary testing has the potential to measure aspects of language without requiring any overt physical or communicative response. Thus, it may be possible to identify the language capabilities and needs of many individuals who have not had access to standardized clinical and research instruments.
The CX-DZ-II intelligent electronic stimulator for neck pain caused by cervical spondylosis: A two-center, randomized, controlled, and non-inferiority trial
Authors: Chen Liping , Li Dehua , Xu Jing , Liang Hao , Zhang Ya , Ren Yulan , Liang Fanrong
Published: July 2022

Background

Electroacupuncture (EA) has been commonly used for the management of neck pain caused by cervical spondylosis (NPCS); however, current electrical instruments have limitations on intelligence, digitalization, and visualization. The intelligent electronic stimulator (CX-DZ-II) is a digital device with an evidence-based diagnosis and treatment system. This study aimed to investigate the efficacy and safety of the CX-DZ-II intelligent EA instrument for NPCS.

Materials and Methods

A total of 164 patients with NPCS [mean age (SD), 49.48 (13.47) years] were randomly assigned to receive 8 sessions (over 2 weeks) EA of the intelligent electronic stimulator (CX-DZ-II) or the regular electronic stimulator (SDZ-II). The primary outcome was the change of the visual analog scale (VAS) from baseline to 2 weeks of treatment. Secondary outcomes included mean scores of the VAS after each treatment in 1 week, responder rate, drug-usage rate of non-steroidal antipyretic analgesics (NSAAs), the occurrence rate of adverse events (AEs), proportions of apparatus with defect during treatment, and excellent rate of apparatus.

Results

The intelligent electronic stimulator (CX-DZ-II) was non-inferior to the regular electronic stimulator (SDZ-II) for changes from baseline in the VAS [3.36 vs. 3.23, with a difference of 0.17 (95% CI, −0.36 to 0.69), P < 0.025 for non-inferiority]. No between-group differences were found in outcomes of VAS in 1 week, overall responders, and drug-usage rate of NSAAs. The defect rate and excellent rate of the instrument were similar in the CX-DZ-II and SDZ-II groups. Adverse events occurred in 9 (10.84%) patients in the CX-DZ-II group and 4 (5.00%) patients in the SDZ-II group.

Conclusion

The intelligent electronic stimulator (CX-DZ-II) was non-inferior to the regular electronic stimulator (SDZ-II) in relieving neck pain. The intelligent electronic stimulator (CX-DZ-II) is a promising non-inferior alternative instrument for NPCS.

Clinical Trial Registration

[https://clinicaltrials.gov/], identifier [NCT030 05301].
Automatic method for individual parcellation of manganese-enhanced magnetic resonance imaging of rat brain
Authors: Bao Zhiguo , Zhang Tianhao , Pan Tingting , Zhang Wei , Zhao Shilun , Liu Hua , Nie Binbin
Published: July 2022

Aims

To construct an automatic method for individual parcellation of manganese-enhanced magnetic resonance imaging (MEMRI) of rat brain with high accuracy, which could preserve the inherent voxel intensity and Regions of interest (ROI) morphological characteristics simultaneously.

Methods and results

The transformation relationship from standardized space to individual space was obtained by firstly normalizing individual image to the Paxinos space and then inversely transformed. On the other hand, all the regions defined in the atlas image were separated and resaved as binary mask images. Then, transforming the mask images into individual space via the inverse transformations and reslicing using the 4th B-spline interpolation algorithm. The boundary of these transformed regions was further refined by image erosion and expansion operator, and finally combined together to generate the individual parcellations. Moreover, two groups of MEMRI images were used for evaluation. We found that the individual parcellations were satisfied, and the inherent image intensity was preserved. The statistical significance of case-control comparisons was further optimized.

Conclusions

We have constructed a new automatic method for individual parcellation of rat brain MEMRI images, which could preserve the inherent voxel intensity and further be beneficial in case-control statistical analyses. This method could also be extended to other imaging modalities, even other experiments species. It would facilitate the accuracy and significance of ROI-based imaging analyses.
Improved Brain Pathology and Progressive Peripheral Neuropathy in a 15 Year Old Survivor of Infantile Krabbe Disease Treated With Umbilical Cord Transplantation
Authors: Kofler Julia , Beltran-Quintero Maria L. , Rugari Anne , Zuccoli Giulio , Klotz Sarah , Escolar Maria L.
Published: July 2022

Objective

Krabbe disease is a fatal leukodystrophy caused by deficiency in galactocerebrosidase enzyme activity. The only currently available therapy is hematopoietic stem cell transplantation with bone marrow or umbilical cord blood (UCBT), which leads to increased lifespan and functional abilities when performed in the preclinical stage. While stabilization of white matter disease has been seen on serial MRI studies, neuropathological changes following transplantation have not been documented so far.

Materials and Methods

We report the first postmortem examination of a 15-year-old female patient with infantile Krabbe disease after UCBT in infancy.

Results

In contrast to an untreated Krabbe disease brain, which showed severe myelin and oligodendrocyte loss with occasional globoid cells, the transplanted brain displayed markedly improved myelin preservation, but not reaching normal myelination levels. Consistent with the transplanted patient’s clinical presentation of pronounced deficits in gross motor skills, corticospinal tracts were most severely affected. No globoid cells or evidence of active demyelination were observed in the central nervous system, indicative of at least partially successful functional restoration. This was corroborated by the identification of male donor-derived cells in the brain by in situ hybridization. Unlike the observed disease stabilization in the central nervous system, the patient experienced progressive peripheral neuropathy. While diminished macrophage infiltration was seen postmortem, peripheral nerves exhibited edema, myelin and axon loss and persistent Schwann cell ultrastructural inclusions.

Conclusion

Umbilical cord blood transplantation was able to alter the natural disease progression in the central but less so in the peripheral nervous system, possibly due to limited cross-correction of Schwann cells.
Upregulation of Netrin-1 in the hippocampus mediates the formation of visceral hypersensitivity induced by maternal separation
Authors: Wang Junwen , Duan Guangbing , Zhan Tingting , Dong Zhiyu , Zhang Yan , Chen Ying , Sun Huihui , Xu Shuchang
Published: July 2022

Early adverse life events (EALs), such as maternal separation (MS), can cause visceral hypersensitivity, which is thought to be a key pathophysiological mechanism of irritable bowel syndrome (IBS). Previous studies mainly focused on EALs-induced visceral hypersensitivity in adulthood but did not consider that it may have occurred in the preadult period. We previously found that rats who experienced MS suffered from visceral hypersensitivity starting from the post-weaning period. Moreover, the hippocampus is considered to be critical in regulating the formation of visceral hypersensitivity induced by MS. But the underlying mechanisms throughout different life periods are unclear. In this study, behavioral tests, RNA-seq, lentiviral interference, and molecular biology techniques were applied to investigate the molecular mechanism in the hippocampus underlying MS-induced long-lasting visceral hypersensitivity. It was found that both visceral sensitivity and anxiety-like behaviors were significantly increased in MS rats in post-weaning, prepubertal, and adult periods, especially in the prepubertal period. Subsequently, RNA-seq targeting the hippocampus identified that the expression level of Netrin-1 was significantly increased in all periods, which was further confirmed by quantitative real-time PCR and Western blot. Knocking-down hippocampal Netrin-1 in the post-weaning period by lentivirus interference alleviated visceral hypersensitivity and anxiety-like behaviors of MS rats in the later phase of life. In addition, deleted in colorectal cancer (DCC), instead of neogenin-1(Neo-1) or uncoordinated (UNC5), was proved to be the specific functional receptor of Netrin-1 in regulating visceral hypersensitivity, whose upregulation may result in the most severe symptoms in the prepubertal period. Furthermore, the activation of the Netrin-1/DCC pathway could enhance long-term potentiation (LTP) in the hippocampus, probably via recruitment of the AMPA receptor subunit GluA1, which finally resulted in the formation of visceral hypersensitivity. These novel findings suggest that long-lasting over-expression of Netrin-1 can mediate visceral hypersensitivity and anxiety disorder from the post-weaning period to adulthood by activating DCC/GluA1 pathway in the hippocampus. Moreover, early intervention of Netrin-1 in the post-weaning period could lead to significant symptom relief afterward, which provides evidence that the Netrin-1/DCC/GluA1 signaling pathway may be a potential therapeutic target for the treatment of visceral hypersensitivity in clinics.
Role of Eryptosis in Hemorrhagic Stroke
Authors: Fang Mei , Xia Fan , Chen Yuqi , Shen Yuke , Ma Lu , You Chao , Tao Chuanyuan , Hu Xin
Published: July 2022

Erythrocytes undergo certain morphological changes resembling apoptosis during senescence or in an abnormal state/site, which is termed eryptosis. This process is characterized by phosphatidylserine (PS) exposure, membrane blebbing, and cell shrinkage. Eryptotic erythrocytes are subsequently removed via macrophage-mediated efferocytosis. In hemorrhagic stroke (HS), blood within an artery rapidly bleeds into the brain tissue or the subarachnoid space, resulting in severe neurological deficits. A hypoxic, over-oxidative, and pro-inflammatory microenvironment in the hematoma leads to oxidative stress, hyperosmotic shock, energy depletion, and Cl– removal in erythrocytes, which eventually triggers eryptosis. In addition, eryptosis following intracerebral hemorrhage favors hematoma clearance, which sheds light on a common mechanism of intrinsic phagocytosis. In this review, we summarized the canonical mechanisms of eryptosis and discussed its pathological conditions associated with HS. Understanding the role of eryptosis in HS may uncover additional potential interventions for further translational clinical research.
An Expanded Framework for Situation Control
Authors: Llinas James , Malhotra Raj
Published: July 2022

There is an extensive body of literature on the topic of estimating situational states, in applications ranging from cyber-defense to military operations to traffic situations and autonomous cars. In the military/defense/intelligence literature, situation assessment seems to be the sine qua non for any research on surveillance and reconnaissance, command and control, and intelligence analysis. Virtually all of this work focuses on assessing the situation-at-the-moment; many if not most of the estimation techniques are based on Data and Information Fusion (DIF) approaches, with some recent schemes employing Artificial Intelligence (AI) and Machine Learning (ML) methods. But estimating and recognizing situational conditions is most often couched in a decision-making, action-taking context, implying that actions may be needed so that certain goal situations will be reached as a result of such actions, or at least that progress toward such goal states will be made. This context thus frames the estimation of situational states in the larger context of a control-loop, with a need to understand the temporal evolution of situational states, not just a snapshot at a given time. Estimating situational dynamics requires the important functions of situation recognition, situation prediction, and situation understanding that are also central to such an integrated estimation + action-taking architecture. The varied processes for all of these combined capabilities lie in a closed-loop “situation control” framework, where the core operations of a stochastic control process involve situation recognition—learning—prediction—situation “error” assessment—and action taking to move the situation to a goal state. We propose several additional functionalities for this closed-loop control process in relation to some prior work on this topic, to include remarks on the integration of control-theoretic principles. Expanded remarks are also made on the state of the art of the schemas and computational technologies for situation recognition, prediction and understanding, as well as the roles for human intelligence in this larger framework.
Home enteral nutrition for patients with esophageal cancer undergoing esophagectomy: A systematic review and meta-analysis
Authors: Zhang Chi , Hu Li-Wen , Qiang Yong , Cong Zhuang-Zhuang , Zheng Chao , Gu Wen-Feng , Luo Chao , Xie Kai , Shen Yi
Published: July 2022

Introduction

Home enteral nutrition (HEN) is a relatively new nutritional intervention that provides patients with EN support at home through jejunostomy or nasogastric feeding tubes. We conducted this systematic review and meta-analysis to explore the safety and effect of HEN compared with normal oral diet (NOD) in postoperative patients with esophageal cancer (EC).

Methods

EMBASE, Medline, Web of Science, and the Cochrane Library were used to search articles in English-language journals. The intervention effect was expressed using risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcome measures, with 95% confidence intervals (95% CIs). The chi-square test and I-square test were used to test heterogeneity among studies.

Results

Four studies were eventually included in this meta-analysis. Compared with NOD, HEN has a favorable impact on postoperative body mass index (BMI) (weighted mean difference [WMD] = 0.70, 95% CI: 0.09–1.30, P = 0.02), lean body mass (LBM) (WMD = 0.76, 95% CI: 0.04–1.48, P = 0.04), and appendicular skeletal muscle mass index (ASMI) (WMD = 0.30, 95% CI: 0.02–0.58, P = 0.03). Physical function (WMD = 9.26, 95% CI: 8.00–10.53, P < 0.001), role function (WMD = 9.96, 95% CI: 8.11–11.82, P < 0.001), and social function (WMD = 8.51, 95% CI: 3.48–13.54, P = 0.001) of the HEN group were better than those of the NOD group at 3 months, and HEN could reduce the fatigue of patients (WMD = −12.73, 95% CI: −14.8 to −10.66, P < 0.001) and the incidence of postoperative pneumonia (RR = 0.53, 95% CI: 0.34–0.81, P = 0.004). There was no significant difference in albumin between HEN and NOD groups (WMD = 0.05, 95% CI: −0.03 to 0.13, P = 0.20).

Conclusion

HEN improved nutritional status and quality of life (QOL) in postoperative patients with EC and reduced fatigue and the incidence of postoperative pneumonia. All in all, the results of our meta-analysis support the use of HEN after esophagectomy.
Flavonoids from Lycium barbarum leaves attenuate obesity through modulating glycolipid levels, oxidative stress, and gut bacterial composition in high-fat diet-fed mice
Authors: Liao JiaLe , Guo Jia , Niu YinHong , Fang Tian , Wang FangZhou , Fan YanLi
Published: July 2022

Traditional herbal therapy made from Lycium barbarum leaves has been said to be effective in treating metabolic diseases, while its exact processes are yet unknown. Natural flavonoids are considered as a secure and reliable method for treating obesity. We thus made an effort to investigate the processes by which flavonoids from L. barbarum leaves (LBLF) reduce obesity. To assess the effectiveness of the intervention following intragastric injection of various dosages of LBLF (50, 100, and 200 mg/kg⋅bw), obese model mice developed via a high-fat diet were utilized. Treatment for LBLF may decrease body weight gain, Lee’s index, serum lipids levels, oxidative stress levels, and hepatic lipids levels. It may also enhance fecal lipids excretion and improve glucose tolerance. Additionally, LBLF therapy significantly restored gut dysfunction brought on by a high-fat diet by boosting gut bacterial diversities and altering the composition of the gut bacterial community by elevating probiotics and reducing harmful bacteria.
Uterine perivascular epithelioid tumors (PEComas) with lung metastasis showed good responses to mTOR and VEGFR inhibitors: A case report
Authors: Sui Chengxu , Wu Jie , Mei Dan , Pan Evenki , Yang Peng , Wu Tingting , Ma Yutong , Ou Qiuxiang , Song Lei
Published: July 2022

Perivascular epithelioid cell tumors (PEComas) are extremely rare mesenchymal neoplasms for which the uterus is the most common site. The prognosis of malignant PEComa is poor as it is characterized by resistance to classical chemotherapies. Both mTOR inhibitors and VEGFR inhibitors exhibited clinical utility in treating malignant PEComas, but the combination of these two regimens has rarely been reported. In the present case, a uterine PEComa patient developed lung and bone metastases after the failure of chemotherapies and derived benefit from the combination regimen of an mTOR inhibitor (everolimus) and a VEGFR inhibitor (apatinib), achieving a 15-month progression-free survival. Targeted NGS revealed TP53 and TSC2 mutations in the patient’s primary uterine tumors and plasma ctDNA at disease progression. Plasma ctDNA clearance was consistent with a radiologic partial response determined by RECIST 1.1 and a reduction of neuron-specific enolase (NSE) and cancer antigen 125 (CA125) levels. Thus, we provided clinical evidence supporting the administration of combined therapy of mTOR and VEGFR inhibitors to metastatic uterine PEComa patients and highlighted the application of serial plasma ctDNA profiling for dynamic disease monitoring.
Differentiation of malignant brain tumor types using intratumoral and peritumoral radiomic features
Authors: Liu Dongming , Chen Jiu , Ge Honglin , Hu Xinhua , Yang Kun , Liu Yong , Hu Guanjie , Luo Bei , Yan Zhen , Song Kun , Xiao Chaoyong , Zou Yuanjie , Zhang Wenbin , Liu Hongyi
Published: July 2022

Tumor infiltration of central nervous system (CNS) malignant tumors may extend beyond visible contrast enhancement. This study explored tumor habitat characteristics in the intratumoral and peritumoral regions to distinguish common malignant brain tumors such as glioblastoma, primary central nervous system lymphoma, and brain metastases. The preoperative MRI data of 200 patients with solitary malignant brain tumors were included from two datasets for training. Quantitative radiomic features from the intratumoral and peritumoral regions were extracted for model training. The performance of the model was evaluated using data (n = 50) from the third clinical center. When combining the intratumoral and peritumoral features, the Adaboost model achieved the best area under the curve (AUC) of 0.91 and accuracy of 76.9% in the test cohort. Based on the optimal features and classifier, the model in the binary classification diagnosis achieves AUC of 0.98 (glioblastoma and lymphoma), 0.86 (lymphoma and metastases), and 0.70 (glioblastoma and metastases) in the test cohort, respectively. In conclusion, quantitative features from non-enhanced peritumoral regions (especially features from the 10-mm margin around the tumor) can provide additional information for the characterization of regional tumoral heterogeneity, which may offer potential value for future individualized assessment of patients with CNS tumors.
A miR-137-XIAP axis contributes to the sensitivity of TRAIL-induced cell death in glioblastoma
Authors: Geng Fenghao , Yang Fen , Liu Fang , Zhao Jianhui , Zhang Rui , Hu Shijie , Zhang Jie , Zhang Xiao
Published: July 2022

Glioblastoma (GBM) is the most lethal primary brain tumor in the central nervous system with limited therapeutic strategies to prolong the survival rate in clinic. TNF-related apoptosis-inducing ligand (TRAIL)-based strategy has been demonstrated to induce cell death in an extensive spectrum of tumor cells, including GBM, while a considerable proportion of malignant cells are resistant to TRAIL-induced apoptosis. MiR-137 is highly expressed in the brain, but significantly decreases with advanced progression of GBM. However, the functional link between miR-137 and TRAIL-induced apoptosis in GBM cells has not been established. Here, GBM cells were transfected with miR-137, and gene expression levels were examined by qRT-PCR and western blot. Apoptotic cells were measured by Annexin-V staining and TUNEL assay. Our data showed that miR-137 sensitizes GBM cells to the TRAIL-mediated apoptosis. Mechanistically, we identified that XIAP is a bona fide target of miR-137, which is essential for miR-137-regulated sensitivity of TRAIL-induced cell death in GBM cells. Finally, in a xenograft model, combined utilization of miR-137 and TRAIL potently suppresses tumor growth in vivo. Collectively, we demonstrate that a miR-137-XIAP axis is required for the sensitivity of TRAIL-induced cell death and shed a light on the avenue for the treatment of GBM.
Trans-Anastomotic Drainage Tube Placement After Hand-Sewn Anastomosis in Patients Undergoing Intersphincteric Resection for Low Rectal Cancer: An Alternative Drainage Method
Authors: Zhong Xinjian , Xie Xiaoyu , Hu Hang , Li Yi , Tian Shunhua , Qian Qun , Jiang Congqing , Ren Xianghai
Published: July 2022

Anastomotic leakage (AL) is a common complication after intersphincteric resection (ISR). It significantly reduces quality of life and causes great distress to patients. Although traditional drainage (e.g., anal and pelvic catheters) may reduce the impact of AL to some extent, their role in reducing the incidence of AL remains controversial. In this study, we developed a novel drainage technique involving the placement of drainage tubes through the gap between sutures during handsewn anastomosis, to reduce the occurrence of anastomotic leakage. We retrospectively analyzed 34 consecutive patients who underwent intersphincteric resection requiring handsewn anastomosis between February 1, 2017, and January 1, 2021. Patients were classified into the trans-anastomotic drainage tube group (TADT, n = 14) and the non-TADT group (n = 20) based on whether trans-anastomotic tube placement was performed. The incidence of postoperative complications, such as AL, was compared between the two groups, and anal function of patients at 1-year post-ISR was evaluated. Six cases of AL occurred in the non-TADT group, while none occurred in the TADT group; this difference was statistically significant (p=0.031). The TADT group also had a shorter hospital stay (p=0.007). There were no other significant intergroup differences in operation time, blood loss, pain score, anastomotic stenosis, intestinal obstruction, or incidence of wound infection. In the 30 patients (88.2%) evaluated for anal function, there were no significant intergroup differences in stool frequency, urgency, daytime/nocturnal soiling, Wexner incontinence score, or Kirwan grading. Taken together, trans-anastomotic tube placement is a novel drainage method that may reduce AL after ISR requiring handsewn anastomosis and without adversely affecting anal function.
Case report: A case of neoadjuvant immunotherapy in combination with the Yang–Monti technique for the treatment of ureteral carcinoma after radical cystectomy and left radical nephroureterectomy
Authors: Wu Tielin , Haleem Harris , Yin Min
Published: July 2022

Recurrence of urothelial carcinoma in a patient with solitary kidney is always a clinical challenge. In the immune checkpoint inhibitor era, neoadjuvant immunotherapy in combination with the Yang–Monti technique might be a good option for the patient with a high-risk tumor when kidney-sparing surgery for renal function preservation is desired. We report the case of a 74-year-old man with solitary kidney who was diagnosed with recurrence of urothelial carcinoma in the right ureter. He was initially deemed unfit for segmental resection of the ureter. Neoadjuvant immunotherapy with tislelizumab was performed in this patient with a partial response to urothelial carcinoma. He underwent segmental resection of the ureter with negative margins, and the ureteral defect was bridged by modified ileal replacement, which is the Yang–Monti technique. This patient has remained disease-free with adequate kidney function for longer than 18 months.
Methods for Establishing a Renal Cell Carcinoma Tumor Spheroid Model With Immune Infiltration for Immunotherapeutic Studies
Authors: Lugand Leonard , Mestrallet Guillaume , Laboureur Rebecca , Dumont Clement , Bouhidel Fatiha , Djouadou Malika , Masson-Lecomte Alexandra , Desgrandchamps Francois , Culine Stephane , Carosella Edgardo D. , Rouas-Freiss Nathalie , LeMaoult Joel
Published: July 2022

Tumor spheroids play an increasingly important role in cancer research. Their ability to recapitulate crucial features of tumor biology that are lost in the classically used 2D models along with their relative simplicity and handiness have made them the most studied 3D tumor model. Their application as a theranostic tool or as a means to study tumor-host interaction is now well-established in various cancers. However, their use in the field of Renal Cell Carcinoma (RCC) remains very limited. The aim of this work is to present methods to implement a basic RCC spheroid model. These methods cover the steps from RCC tumor dissociation to spheroid infiltration by immune cells. We present a protocol for RCC dissociation using Liberase TM and introduce a culture medium containing Epithelial Growth Factor and Hydrocortisone allowing for faster growth of RCC primary cells. We show that the liquid overlay technique allows for the formation of spheroids from cell lines and from primary cultures. We present a method using morphological criteria to select a homogeneous spheroid population based on a Fiji macro. We then show that spheroids can be infiltrated by PBMCs after activation with OKT3 or IL-15. Finally, we provide an example of application by implementing an immune spheroid killing assay allowing observing increased spheroid destruction after treatment with PD-1 inhibitors. Thus the straightforward methods presented here allow for efficient spheroid formation for a simple RCC 3D model that can be standardized and infused with immune cells to study immunotherapies.
A novel HCC prognosis predictor PDSS1 affects the cell cycle through the STAT3 signaling pathway in HCC
Authors: Rao Zuqin , Li Heng , Yao Wenchao , Wang Qiang , Ma Biao , Xue Dongbo , Meng Xianzhi
Published: July 2022

Decaprenyl diphosphate synthase subunit 1 (PDSS1) is closely related to a variety of human diseases, but its expression pattern and biological function in HCC have not been studied to date.

Methods

The expression level of PDSS1 was analyzed using the TCGA and GEO databases. The relationships between PDSS1 and patient clinicopathological characteristics were verified based on TCGA clinical data. Additionally, the co-expressed genes of PDSS1were investigated and Gene Set Enrichment Analysis (GSEA) was conducted using LinkedOmics. Next, the association between PDSS1 and immune infiltration was determined using version 1.34.0 of the GSVA package. EdU assay, colony-formation assay, transwell assay, wound-healing assay, and flow cytometry analysis were used to assess the effect of PDSS1 on the cell phenotype.

Results

PDSS1 was upregulated in HCC compared with adjacent tissues. High PDSS1 in HCC was associated with poor overall survival, disease-specific survival, and progress-free interval. Results suggested that PDSS1 may activate multiple oncogenic pathways in HCC, especially those involved in the cell cycle. The expression of PDSS1 was significantly related to Th2 cells, TFH, T helper cells, NK CD56bright cells, cytotoxic cells, DC, CD8 T cells, and neutrophils. PDSS1 knockdown inhibited cell proliferation, cell cycle, migration and invasion. Furthermore, PDSS1 acted as an oncogene through the STAT3 signaling pathway.

Conclusion

Our study reveals that a high level of PDSS1 is significantly correlated with poor patient prognosis and immune cell infiltration in HCC. PDSS1 may be a novel biomarker and potential therapeutic target for HCC.
Long-term clinical outcomes and prognostic factors of upfront surgery as a first-line therapy in biopsy-proven clinical N2 non-small cell lung cancer
Authors: Bertolaccini Luca , Prisciandaro Elena , Guarize Juliana , Girelli Lara , Sedda Giulia , Filippi Niccolò , de Marinis Filippo , Spaggiari Lorenzo
Published: July 2022

Background

Multimodality therapy offers the best opportunity to improve pathological N2 non-small cell lung cancer (NSCLC) prognosis. This paper aimed to evaluate the long-term clinical outcomes and the prognostic factors of upfront surgery as first-line therapy in biopsy-proven clinical N2.

Methods

Retrospective review of biopsy-proven cN2 NSCLC patients operated between 2007 and 2017. Upfront surgery was considered if the primary tumour was deemed completely resectable, with mediastinal nodal involvement confined to a single station and no preoperative evidence of extranodal tumour invasion.

Results

Two hundred eighty-five patients who underwent radical resections were included. One hundred fifty-nine patients (55.8%) received induction chemotherapy. At follow-up completion, 127 (44.6%) patients had died. For the induction chemotherapy group, the median overall survival (OS) was 49 months [95% confidence interval (CI): 38–70 months], and the 5-year OS was 44.4%. The median and 5-year OS for the up front surgery group was 66 months (95% CI: 40–119 months) and 66.3%, respectively. There were no statistically significant differences between treatment approaches (p = 0.48). One hundred thirty-four patients (47.0%) developed recurrence. The recurrence-free survival (RFS) at 5 years was 17% (95% CI: 11–25%) for induction chemotherapy and 22% (95% CI: 9–32%) for upfront surgery; there were no statistically significant differences between groups (p = 0.93). No significant differences were observed based on the clinical N status (OS, p = 0.36; RFS, p = 0.65).

Conclusions

Upfront surgery as first-line therapy for biopsy-proven cN2 NSCLC showed favourable clinical outcomes, similar to those obtained after induction chemotherapy followed by surgery. Therefore, it should be considered one of the multimodality treatment options in resectable N2 NSCLC.
Prophylactic Central Neck Dissection to Improve Disease-Free Survival in Pediatric Papillary Thyroid Cancer
Authors: Ngo Duy Quoc , Le Duong The , Le Quang
Published: July 2022

Background

Pediatric PTC is a rare disease. Although, the prognosis is excellent and the mortality rate is low, the role of prophylactic central neck dissection is still the subject of debate. The aim was to evaluate both the role and safety of prophylactic central neck dissection (CND) in managing pediatric papillary thyroid cancer (PTC), especially in respect of disease-free survival (DFS).

Patients and Methods

In this retrospective study, we collected 54 pediatric cN0 PTC patients (≤ 18 years of age) who were treated from January 2014 to January 2021 at a high-volume thyroid surgery center. Patients were divided into two groups based on the status of prophylactic CND. We analyzed the factors related to the clinicopathological features and recurrence of PTC in children.

Results

Of the 54 cN0 patients, 35 underwent prophylactic CND and 19 patients did not undergo prophylactic CND. The two groups were similar in clinical and pathologic features, such as age, gender, tumor size, multifocal status, and follow-up time. The average DFS was 84.4 ± 2.7 months. Log-rank tests on Kaplan-Meier curves revealed that age, gender, tumor size, multifocality, and extrathyroid extension did not relate to DFS time. Furthermore, DFS time was not affected by the extent of thyroidectomy (p=0.07) or RAI treatment (p=0.21). Prophylactic CND was found to increase DFS time for pediatric patients with cN0 PTC (p = 0.003). There was no statistically significant difference in complications such as transient hypocalcemia (p=0.15) and transient recurrent laryngeal nerve injury (p=0.37) between the prophylactic CND group and the no-prophylactic CND group.

Conclusion

Prophylactic CND was found to be associated with increased DFS and not with increased rates of complications after surgery.
Epigenome-wide gene–age interaction study reveals reversed effects of MORN1 DNA methylation on survival between young and elderly oral squamous cell carcinoma patients
Authors: Xu Ziang , Gu Yan , Chen Jiajin , Chen Xinlei , Song Yunjie , Fan Juanjuan , Ji Xinyu , Li Yanyan , Zhang Wei , Zhang Ruyang
Published: July 2022

DNA methylation serves as a reversible and prognostic biomarker for oral squamous cell carcinoma (OSCC) patients. It is unclear whether the effect of DNA methylation on OSCC overall survival varies with age. As a result, we performed a two-phase gene–age interaction study of OSCC prognosis on an epigenome-wide scale using the Cox proportional hazards model. We identified one CpG probe, cg11676291MORN1, whose effect was significantly modified by age (HRdiscovery = 1.018, p = 4.07 × 10−07, FDR-q = 3.67 × 10−02; HRvalidation = 1.058, p = 8.09 × 10−03; HRcombined = 1.019, p = 7.36 × 10−10). Moreover, there was an antagonistic interaction between hypomethylation of cg11676291MORN1 and age (HRinteraction = 0.284; 95% CI, 0.135–0.597; p = 9.04 × 10−04). The prognosis of OSCC patients was well discriminated by the prognostic score incorporating cg11676291MORN1–age interaction (HRhigh vs. low = 3.66, 95% CI: 2.40–5.60, p = 1.93 × 10−09). By adding 24 significant gene–age interactions using a looser criterion, we significantly improved the area under the receiver operating characteristic curve (AUC) of the model at 3- and 5-year prognostic prediction (AUC3-year = 0.80, AUC5-year = 0.79, C-index = 0.75). Our study identified a significant interaction between cg11676291MORN1 and age on OSCC survival, providing a potential therapeutic target for OSCC patients.
Pathological characteristics and predictive factors of prostate biopsy in patients with serum PSA levels between 0 and 4.0 ng/ml
Authors: Su Rui , Pan Jin-feng , Ren Da-wei , Jiang Jun-hui , Ma Qi
Published: July 2022

Background

This study aimed to analyze the pathological characteristics and predictive factors of prostate biopsy in men with PSA levels below 4.0 ng/ml.

Patients and methods

We retrospectively analyzed 158 patients who underwent prostate biopsy with PSA levels below 4.0 ng/ml. Pathological results were statistically analyzed. The logistic regression analysis was used to determine the predictive factors for malignant outcomes. Subgroup analysis was performed on patients who received surgery and the postoperative pathological upgrading was counted.

Results

A total of 143 patients were enrolled. The tumor detection rate was 20.3%. Among these patients, most of them (79.3%) had prostate adenocarcinoma, but rare malignant tumors also accounted for 20.7%. Logistic regression analysis indicated that the only independent predictive factor for a positive prostate biopsy was the PI-RADS score. For prostate adenocarcinoma cases, 95.7% of them were organ localized and 47.8% of cases were clinically significant. Subgroup analysis was performed on 14 patients who received surgical treatment. 28.6% of patients were upgraded to clinically significant prostate cancer, while 64.3% of patients had an upgrade in tumor stage.

Conclusion

Our study indicated that 20.3% of men with PSA levels between 0 and 4.0 ng/ml were diagnosed with prostate malignancies. Among these patients, most of them (79.3%) were diagnosed with prostate adenocarcinoma, and several uncommon types of malignancies were also detected in 20.7% of patients. The only risk factor for a positive biopsy in patients with a low PSA concentration was the PI-RADS score. It should be emphasized that the invasiveness of PCa patients diagnosed by biopsy may be underestimated as more than half of patients will upgrade their Gleason score or clinical stages after surgery. Thus, clinicians should pay more attention to patients with PSA levels between 0 and 4.0 ng/ml.
Local and systemic therapy may be safely de-escalated in elderly breast cancer patients in China: A retrospective cohort study
Authors: Wang Ji , Fu Hongtao , Zhong Zhaoyun , Jiang Yunshan , Pan Hong , Sun Xiaowei , Xu Weiwei , Tang Xinyu , Zhou Wenbin , Wang Shui
Published: July 2022

Background

For elderly patients with breast cancer, the treatment strategy is still controversial. In China, preoperative axillary lymph node needle biopsy is not widely used, resulting in many patients receiving axillary lymph node dissection (ALND) directly. Our study aims to determine whether local and systemic therapy can be safely de-escalated in elderly breast cancer.

Methods

Patients aged ≥70 years were retrospectively enrolled from our institution’s medical records between May 2013 and July 2021. Groups were assigned according to local and systemic treatment regimens, and stratified analysis was performed by molecular subtypes. Univariate and multivariate survival analyses were used to compare the effects of different regimens on relapse-free survival (RFS).

Results

A total of 653 patients were enrolled for preliminary data analysis, and 563 patients were screened for survival analysis. The mean follow-up was 19 months (range, 1–82 months). Axillary lymph node metastases were pathologically confirmed in only 2.1% of cN0 cases and up to 97.1% of cN+ cases. In the aspect of breast surgery, RFS showed no significant difference between mastectomy and BCS group (p = 0.3078). As for axillary surgery, patients in the ALND group showed significantly better RFS than those in the sentinel lymph node biopsy (SLNB) group among pN0 patients (p = 0.0128). Among these cases, the proportion of cN+ in ALND was significantly higher than that in SLNB (6.4% vs. 0.4%, p = 0.002), which meant axillary lymph nodes (ALNs) of ALND patients were larger in imaging and more likely to be misdiagnosed as metastatic. With regard to adjuvant therapy, univariate and multivariate analyses showed that RFS in different comprehensive adjuvant regimens were similar especially among hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)− subgroup where patients who did not receive any adjuvant therapy accounted for 15.7% (p > 0.05).

Conclusions

It is feasible to reduce some unnecessary local or systemic treatments for elderly breast cancer patients, especially in HR+/HER2− subtype. Multiple patient-related factors should be considered when making treatment plans.
Association between hashimoto thyroiditis and differentiated thyroid cancer: A single-center experience
Authors: Cappellacci Federico , Canu Gian Luigi , Lai Maria Letizia , Lori Eleonora , Biancu Miriam , Boi Francesco , Medas Fabio
Published: July 2022

Hashimoto’s thyroiditis is the most common cause of hypothyroidism in the iodine-sufficient areas of the world. Differentiated thyroid cancer is the most common thyroid cancer subtype, accounting for more than 95% of cases, and it is considered a tumor with a good prognosis, although a certain number of patients experience a poor clinical outcome. Hashimoto’s thyroiditis has been found to coexist with differentiated thyroid cancer in surgical specimens, but the relationship between these two entities has not yet been clarified. Our study aims to analyze the relationship between these two diseases, highlighting the incidence of histological diagnosis of Hashimoto thyroiditis in differentiated thyroid cancer patients, and assess how this autoimmune disorder influences the risk of structural disease recurrence and recurrence rate.