bluuebunny/crossref_metadata_2025 huggingface dataset:
Pan-cancer analysis and experimental validation of DTL as a potential diagnosis, prognosis and immunotherapy biomarker
Authors: Tang Yumei , Lei Ye , Gao Peng , Jia Junting , Du Huijun , Wang Qitong , Yan Zhixin , Zhang Chen , Liang Guojun , Wang Yanfeng , Ma Weijun , Xing Nianzeng , Cheng Le , Ren Laifeng
Published: April 2023

Background

DTL has been found to be related with multiple cancers. However, comprehensive analyses, which identify the prediction value of DTL in diagnosis, prognosis, immune infiltration and treatment, have rarely been reported so far.

Methods

Combined with the data online databases, the gene expression, gene mutation, function enrichment and the correlations with the immunity status and clinical indexes of DTL were analyzed. Expression of DTL and the degree of immune cell infiltration were examined by immunofluorescence (IF) and immunohistochemistry (IHC) and analyzed by statistical analysis. Furthermore, the influences of DTL on the cell cycle, cell proliferation and apoptosis were detected by live cell imaging, IF and flow cytometric (FC) analysis. Genomic stability assays were conducted by chromosome slide preparation.

Results

DTL was widely expressed in various cells and tissues, while it was overexpressed in tumor tissues except acute myeloid leukemia (LAML). Pan-cancer bioinformatics analysis showed that the expression of DTL was correlated with the prognosis, immunotherapy, and clinical indexes in various cancers. In addition, gene set enrichment analysis (GSEA) uncovered that DTL was enriched in oocyte meiosis, pyrimidine metabolism, the cell cycle, the G2M checkpoint, mTORC1 signaling and E2F targets. Furthermore, the overexpression of DTL, and its association with immune cell infiltration and clinical indexes in liver hepatocellular carcinoma (LIHC), bladder urothelial carcinoma (BLCA) and stomach adenocarcinoma (STAD) were verified in our study. It was also verified that overexpression of DTL could regulate the cell cycle, promote cell proliferation and cause genomic instability in cultured cells, which may be the reason why DTL plays a role in the occurrence, progression and treatment of cancer.

Conclusions

Collectively, this study suggested that DTL is of clinical value in the diagnosis, prognosis and treatment of various cancers, and may be a potential biomarker in certain cancers.
Higher Soong grade predicts flexor tendon issues after volar plating of distal radius fractures – a retrospective cohort study
Authors: Vasara Henri , Tarkiainen Petra , Stenroos Antti , Kosola Jussi , Anttila Turkka , Aavikko Anni , Nordback Panu H , Aspinen Samuli
Published: April 2023

Background and purpose

Soong classification is used to estimate volar locking plate prominence and evaluate the risk for flexor tendon ruptures after surgical treatment of distal radius fractures (DRFs). However, the scientific community has questioned the Soong classification due to lacking evidence. Therefore, this study aimed to evaluate the accuracy of Soong grading as a predictor for flexor tendon issues and plate removal.

Patients and methods

We performed a retrospective single-center review of adult distal radius fracture patients treated with a volar locking plate between 2009 and 2019. In total, 2779 patients were included in the study. The primary outcome was a flexor tendon issue (flexor tendon rupture, tendinitis, or flexor irritation), whereas plate removal was a secondary outcome. Using Soong grade 0 as a reference, we used univariable and multivariable logistic regression to calculate odds ratios (OR) with 95% confidence intervals (CI) for flexor tendon issues and plate removal.

Results

In total, 756 (27%) patients were graded as Soong 0, 1679 (60%) Soong 1, and 344 (12%) Soong 2, respectively. There were 32 (1.2%) patients with flexor tendon issues, of which 4 were flexor tendon ruptures, 8 tendinitises, and 20 flexor irritations. The adjusted OR for flexor tendon issues was 4.4 (CI 1.1–39.7) for Soong grade 1 and 9.7 (CI 2.2–91.1) for Soong grade 2. The plate was removed from 167 (6.0%) patients. Soong grade 1 had a univariable OR of 1.8 (CI 1.2–2.8) for plate removal, and Soong grade 2 had an OR of 3.5. (CI 2.1–5.8), respectively.

Conclusion

Flexor tendon ruptures are rare complications after the volar plating of DRFs. A higher Soong grade is a risk factor for flexor tendon issues and plate removal.

Trial registration

The trial was retrospectively registered.
Implementation of an online pain science education for chronic musculoskeletal pain in Brazilian public health system: protocol for a hybrid type III randomised controlled trial with economic evaluation
Authors: Baroni Marina P. , Hespanhol Luiz , Miyamoto Gisela C. , Daniel Christiane R. , Fernandes Lívia G. , dos Reis Felipe J. J. , Pate Joshua W. , Saragiotto Bruno T.
Published: April 2023

Background

Although clinical practice guidelines recommend pain education as the first-line option for the management of chronic musculoskeletal pain, there is a lack of pain education programmes in healthcare. Thus, digital health programmes can be an effective tool for implementing pain education strategies for public health. This trial will aim to analyse the implementation and effectiveness outcomes of three online pain science education strategies in the Brazilian public health system (SUS) for individuals with chronic musculoskeletal pain.

Methods

We will conduct a hybrid type III effectiveness-implementation randomised controlled trial with economic evaluation. We will include adult individuals with chronic musculoskeletal pain, recruited from primary healthcare in the city of Guarapuava, Brazil. Individuals will be randomised to three implementation groups receiving a pain science education intervention (EducaDor) but delivered in different modalities: group 1) synchronous online; group 2) asynchronous videos; and group 3) interactive e-book only. Implementation outcomes will include acceptability, appropriateness, feasibility, adoption, fidelity, penetration, sustainability, and costs. We will also assess effectiveness outcomes, such as pain, function, quality of life, sleep, self-efficacy, and adverse effects. Cost-effectiveness and cost-utility analyses will be conducted from the SUS and societal perspectives. The evaluations will be done at baseline, post-intervention (10 weeks), and 6 months.

Discussion

This study will develop and implement a collaborative intervention model involving primary healthcare professionals, secondary-level healthcare providers, and patients to enhance self-management of chronic pain. In addition to promoting better pain management, this study will also contribute to the field of implementation science in public health by generating important insights and recommendations for future interventions.

Trial registration

ClinicalTrials.gov (NCT05302180; 03/29/2022).
Comparison of surgical invasiveness, hidden blood loss, and clinical outcome between unilateral biportal endoscopic and minimally invasive transforaminal lumbar interbody fusion for lumbar degenerative disease: a retrospective cohort study
Authors: Huang Xinle , Wang Wenkai , Chen Guangxing , Guan Xiangchen , Zhou Yue , Tang Yu
Published: April 2023

Background

Currently, hidden blood loss (HBL) has been paid more and more attention by spine surgeons. Simultaneously, it has been the effort of spine surgeons to explore more advantages of minimally invasive surgery. More and more articles have compared unilateral biportal endoscopic lumbar interbody fusion (BE-LIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). But so far, there is no HBL comparison between BE-LIF and MIS-TLIF. This study aims to compare the surgical invasiveness, hidden blood loss, and clinical outcome of BE-LIF and MIS-TLIF and to provide insight regarding minimally invasive surgery for lumbar degenerative disease (LDD).

Methods

We enrolled 103 eligible patients with LDD who underwent BE-LIF (n = 46) and MIS-TLIF (n = 57) during August 2020–March 2021. We collected data, including demographics, perioperative haematocrit, operative and postoperative hospital times, serum creatine kinase (CK) and C-reactive protein (CRP) levels, and hospitalization costs. Total and hidden blood loss was calculated. Clinical outcomes were assessed using a visual analogue scale (VAS) score for back and leg pain, Oswestry Disability Index (ODI), modified MacNab criteria, fusion rate, and complications.

Results

Basic demographics and surgical data were comparable. The CRP and CK levels were generally lower in the BE-LIF than in the MIS-TLIF group, especially CRP levels on postoperative day (POD) three and CK levels on POD one. True total blood loss, postoperative blood loss, and hidden blood loss were significantly reduced in the BE-LIF group compared with the MIS-TLIF group. Postoperative hospital times was statistically significantly shorter in the BE-LIF group. The VAS pain and ODI scores improved in both groups. At three days and one month, the VAS lower back pain scores were significantly better after BE-LIF. Clinical outcomes did not otherwise differ between groups.

Conclusions

Compared with MIS-TLIF, BE-LIF has similar medium and short-term clinical outcomes. However, it is better regarding surgical trauma, early lower back pain, total and hidden blood loss, and recovery time. BE-LIF is an adequate option for selected LDD.
Allogeneic tendons in the treatment of malunited lateral malleolar avulsion fractures with chronic lateral ankle instability
Authors: Zhang Yu , Wang Xin , Wang Xiaomeng , Cao Jianming , Wang Huijuan , Zhang Fengqi
Published: April 2023

Background

The aim of this study is to report our institution’s experience regarding the application of allogeneic tendons for the reconstruction of malunited lateral malleolar avulsion fractures with chronic lateral ankle instability.

Methods

This retrospective study included 34 (34 ankles) patients surgically treated for malunited lateral malleolar avulsion fractures with chronic lateral ankle instability from January 2016 to December 2019. All patients underwent allogeneic tendon reconstruction. The pre- and postoperative American Orthopaedic Foot and Ankle Society (AOFAS) scores、Karlsson Ankle Functional Scores (KAFS) and visual analogue scale (VAS) scores were used to evaluate the functional recovery of the ankle joint. The final follow-up, based on radiographic assessment, including talar tilt and anterior talar translation, was performed to evaluate the stability of the postoperative ankle joints.

Results

Thirty-two patients (32 ankles) returned for final clinical and radiologic follow-up at an average of 29 (range 24–35) months and 2 patients (2 ankles) were lost to follow-up. The preoperative talus inclination angle (13.6 ± 1.9°) and anterior displacement (9.6 ± 2.8 mm) were re-examined under X-ray and found to be reduced to 3.4 ± 1.2° and 3.8 ± 1.1 mm, respectively (p＜0.01). The AOFAS scores increased from 58.5 ± 4.0 to 90.9 ± 3.8 and the Karlsson scores improved from 52.2 ± 3.6 to 89.8 ± 4.5, which was obviously better and the difference was statistically significant (P < 0.01). The VAS scores were significantly reduced from a preoperative mean of 6.8 ± 1.0 to 2.8 ± 0.9 postoperatively (p＜0.01).

Conclusion

In this population and with this follow-up, the application of allogeneic tendons to treat malunited lateral malleolar avulsion fractures combined with chronic lateral ankle instability appeared safe and effective.
Effect of palliative care decisions making on hospital service use at end-of-life in patients with malignant brain tumors: a retrospective study
Authors: Nåhls Nelli-Sofia , Leskelä Riikka-Leena , Saarto Tiina , Hirvonen Outi , Anttonen Anu
Published: April 2023

Background

Palliative care (PC) improves Quality of life and reduces the symptom burden. Aggressive treatments at end of life (EOL) postpone PC. The aim of this single-center retrospective study was to evaluate the timing of the PC decision i.e., termination of cancer-specific treatments and focusing on symptom-centered PC, and its impact on the use of tertiary hospital services at the EOL.

Methods

A retrospective cohort study on brain tumor patients, who were treated at the Comprehensive Cancer Center of the Helsinki University Hospital from November 1993 to December 2014 and died between January 2013 and December 2014, were retrospectively reviewed. The analysis comprised 121 patients (76 glioblastoma multiforme, 74 males; mean age 62 years; range 26–89). The decision for PC, emergency department (ED) visits and hospitalizations were collected from hospital records.

Results

The PC decision was made for 78% of the patients. The median survival after diagnosis was 16 months (13 months patients with glioblastoma), and after the PC decision, it was 44 days (range 1-293). 31% of the patients received anticancer treatments within 30 days and 17% within the last 14 day before death. 22% of the patients visited an ED, and 17% were hospitalized during the last 30 days of life. Of the patients who had a PC decision made more than 30 days prior to death, only 4% visited an ED or were hospitalized in a tertiary hospital in the last 30 days of life compared to patients with a late (< 30 days prior to death) or no PC decision (25 patients, 36%).

Conclusions

Every third patient with malignant brain tumors had anticancer treatments during the last month of life with a significant number of ED visits and hospitalizations. Postponing the PC decision to the last month of life increases the risk of tertiary hospital resource use at EOL.
What do health care professionals want to know about assisted dying? Setting the research agenda in New Zealand
Authors: Young Jessica , Snelling Jeanne , Beaumont Sophie , Diesfeld Kate , White Ben , Willmott Lindy , Robinson Jacqualine , Ahuriri-Driscoll Annabel , Cheung Gary , Dehkhoda Aida , Egan Richard , Jap James , Karaka-Clarke Te Hurinui , Manson Leanne , McLaren Cam , Winters Janine
Published: April 2023

Background

New Zealand recently introduced law permitting terminally ill people to request and receive assisted dying (AD) in specified circumstances. Given the nature and complexity of this new health service, research is vital to determine how AD is operating in practice.

Objective

To identify research priorities regarding the implementation and delivery of AD in New Zealand.

Methods

Using an adapted research prioritisation methodology, the researchers identified 15 potential AD research topics. A mixed-methods survey of health professionals was undertaken where respondents were asked to rate the 15 topics according to the relative importance for research to be conducted on each issue. Respondents could also suggest additional research areas, and were invited to participate in a follow-up interview.

Results

One hundred and nineteen respondents completed the survey. 31% had some experience with AD. The highest rated research topic was the ‘effectiveness of safeguards in the Act to protect people’; the lowest rated topic was research into the ‘experiences of non-provider (e.g., administrative, cleaning) staff where assisted dying is being provided’. Respondents suggested 49 other research topics. Twenty-six interviews were conducted. Thematic analysis of interview data and open-ended survey questions was undertaken. Six research themes were identified: general factors related to the wider health system; the experiences of health care providers at the bedside; medico-legal issues; the impact of AD; experiences on the day of dying; and the overall effectiveness of the AD system. Key issues for stakeholders included safety of the AD service; ensuring access to AD; achieving equity for ‘structurally disadvantaged’ groups; and ensuring the well-being of patients, families/whānau, providers and non-providers.

Conclusions

Based on early experiences of the implementation of the AD service, health professionals provide important insights into what research should be prioritised post-legalisation of AD. These findings can be used to shape the research agenda so that research may inform law, policy and best practice.
Cancer immunotherapy with immune checkpoint inhibitors (ICIs): potential, mechanisms of resistance, and strategies for reinvigorating T cell responsiveness when resistance is acquired
Authors: Marei Hany E. , Hasan Anwarul , Pozzoli Giacomo , Cenciarelli Carlo
Published: April 2023

Cancer is still the leading cause of death globally. The approval of the therapeutic use of monoclonal antibodies against immune checkpoint molecules, notably those that target the proteins PD-1 and PD-L1, has changed the landscape of cancer treatment. In particular, first-line PD-1/PD-L1 inhibitor drugs are increasingly common for the treatment of metastatic cancer, significantly prolonging patient survival. Despite the benefits brought by immune checkpoint inhibitors (ICIs)-based therapy, the majority of patients had their diseases worsen following a promising initial response. To increase the effectiveness of ICIs and advance our understanding of the mechanisms causing cancer resistance, it is crucial to find new, effective, and tolerable combination treatments. In this article, we addressed the potential of ICIs for the treatment of solid tumors and offer some insight into the molecular pathways behind therapeutic resistance to ICIs. We also discuss cutting-edge therapeutic methods for reactivating T-cell responsiveness after resistance has been established.
ATG4B and pS383/392-ATG4B serve as potential biomarkers and therapeutic targets of colorectal cancer
Authors: Hu Wan-Hsiang , Liu Ting-Ting , Liu Pei-Feng , Morgan Paul , Lin I-Ling , Tsai Wei-Lun , Cheng Yi-Yun , Hsieh Ang-Tsen , Hu Tsung-Hui , Shu Chih-Wen
Published: April 2023

Background

Autophagy related protease 4B (ATG4B) is a protease required for autophagy processing, which is strongly implicated in cancer progression.  Phosphorylation of ATG4B is crucial for activation of its protease activity.  However, little is known about the relationship of ATG4B and its phosphorylated form at Ser 383 and 392 sites (pS383/392-ATG4B), with clinical outcomes, particularly in colorectal cancer (CRC).

Methods

The ATG4B gene expression in CRC patients was obtained from The Cancer Genome Atlas (TCGA) database to analyze its clinical relevance. Tissue microarrays composed of 118 CRC patient specimens were used to determine the associations of ATG4B and pS383/392-ATG4B protein levels with prognosis. The biological functions of ATG4B in CRC cells were inspected with cell proliferation, mobility and spheroid culture assays.

Results

ATG4B gene expression was elevated in tumor tissues of CRC patients compared to that in adjacent normal tissues and high level of ATG4B expression was associated with poor survival. Similarly, protein levels of ATG4B and pS383/392-ATG4B were highly correlated with worse overall survival and disease-free survival. Stratification analysis results showed that high level of ATG4B had significantly higher risk of mortality in males and elderly patients compared to those female patients and patients 60 years or younger. In contrast, multivariate Cox’s regression analysis indicated that high level of pS383/392-ATG4B was significantly linked to unfavorable overall survival and disease-free survival of males and elderly patients, whereas, it had no correlation with female patients and patients 60 years or younger. Moreover, high level of ATG4B was positively associated with increased mortality risk in patients with advanced AJCC stages (III and IV) and lymph node invasion (N1 and N2) for both overall survival and disease-free survival. Nevertheless, high level of pS383/392-ATG4B was positively correlated with increased mortality risk in patients with early AJCC stages (I and II) and without lymph node invasion (N0). In addition, silencing ATG4B attenuated migration, invasion, and further enhanced the cytotoxic effects of chemotherapeutic drugs in two and three-dimensional cultures of CRC cells.

Conclusions

Our results suggest that ATG4B and pS383/392-ATG4B might be suitable biomarkers and therapeutic targets for CRC.
Family and domestic violence policy discourses and narratives: implications for Emergency Departments and communities in rural Australia
Authors: Moore Sheree , Fox Rachael , Nic Giolla Easpaig Bróna , Deravin Linda
Published: April 2023

Background

Australian data has indicated that the frequency and severity of family and domestic violence (FDV) tends to increase with remoteness. Rural communities rely on Emergency Departments (ED) within public hospitals for general health and safety needs. Public health departments within Australia are strongly influenced by Government policies which can define ‘health problems’ and limit institutional responses to patients presenting with FDV. The current study therefore aimed to critically examine FDV Australian Government policies to explore how policy meanings could potentially impact on ED staff and individuals within rural communities.

Methods

Foucauldian Discourse Analysis and Policy Narrative Analysis were used to examine 9 policy documents which represented national, state/territory and clinical practice levels. Publication dates ranged from 2006 to 2020.

Results

A total of 8 discourses were identified, with each one providing a unique construction of the target problem and determining the potential agency of health professionals and subjects of FDV. Discourses combined to produce an overall narrative within each policy document. Narrative constructions of the target problem were compared which produced three narrative themes: 1) Deficit Subject Narratives; 2) Object Oriented Narratives; and 3) Societal Narratives.

Conclusion

The results reflected a transition in the meaning of FDV within Australian society and over the past decade, with policies trending away from Deficit Subject Narratives and towards Object Oriented or Societal Narratives. Institutional systems, sociohistorical context and broader societal movements may have shaped this transition by stagnating policy meanings or introducing new insights that expanded the possibilities of understanding and action. Narratives produced assumptions which significantly altered the relevance and agency of individuals and groups when applied to a rural ED setting. As FDV was moved out of the clinical space and into the public domain, the agency of health professionals was reduced, while the values and strengths of FDV subjects and rural communities were potentially recognised. Later policies provided contextual specificity and meaning fluidity that could benefit diverse groups within rural areas; however, the expectation for ED staff to learn from their communities and challenge institutionalised approaches to FDV requires careful consideration in relation to rural hospital systems and resources.
The buffering effect of social capital for daily mental stress in an unequal society: a lesson from Seoul
Authors: Kang Sungik , Lee Joo-Lim , Koo Ja-Hoon
Published: April 2023

This study attempted to illustrate whether mental health deterioration could be alleviated by high social capital in an environment with high economic inequality. Daily mental stress was employed as a mental health factor when analyzing the association with economic inequality in the Seoul Survey data. Regarding social capital, community trust and altruism were included as cognitive dimensions, and participation and cooperation were included as structural dimensions in each model. The first finding showed a significantly positive relationship between economic inequality and daily stress, meaning that, like other mental health problems, daily mental stress is also high in regions with high economic inequality. Second, the slope of the daily stress increased in respondents with high social trust and participation was alleviated in an economically unequal environment. This indicates that social trust and participation have a buffering effect by moderating the slope of daily stress in societies with high inequality. Third, the buffering effect differs depending on the social capital factor. The buffering effect of trust and participation showed in an unequal environment, while the buffering effect of cooperation showed regardless of the unequal environment. In summary, social capital factors showed the effect of relieving daily mental stress in the relationship with economic inequality. Also, the buffering effect of social capital on mental health may show different aspects for each element.
Experience-based health state valuation using the EQ VAS: a register-based study of the EQ-5D-3L among nine patient groups in Sweden
Authors: Teni Fitsum Sebsibe , Burström Kristina , Devlin Nancy , Parkin David , Rolfson Ola ,   The Swedish Quality Register (SWEQR) Study Group, Abbott Allan , Ekström Magnus , Forssblad Magnus , Fritzell Peter , Jonsson Åsa , Landén Mikael , Möller Michael , Regardt Malin , Rosengren Björn , Schmitt-Egenolf Marcus , Vinblad Johanna , W-Dahl Annette
Published: April 2023

Background

The EQ VAS component of the EQ-5D questionnaire has been used to assess patients’ valuation of their own health besides its use for self-reporting of overall health status. The objective of the present study was to identify patients’ valuation of EQ-5D-3L health states using the EQ VAS in different patient groups over time and in comparison to the general population.

Methods

Data were obtained from patients from nine National Quality Registers (n = 172,070 patients) at baseline and at 1-year follow-up and compared with data from the general population (n = 41,761 participants). The correlation between EQ VAS scores and EQ-5D-3L index based on the Swedish experience-based VAS value set was assessed. Ordinary least squares (OLS) regression models were used to determine the association between EQ-5D-3L dimensions and EQ VAS valuation.

Results

EQ VAS scores showed consistency with severity of health states both at baseline and at 1-year follow-up in the nine selected EQ-5D-3L health states. The regression models showed mostly consistent decrements by severity levels in each dimension at both time points and similar to the general population. The dimension mainly associated with inconsistency was the self-care severity level three. Problems in the anxiety/depression dimension had the largest impact on overall health status in most of the patient groups and the general population.

Conclusion

The study has demonstrated the important role EQ VAS can play in revealing patients’ valuation of their health and showed the variation in valuation of EQ-5D-3L dimensions and levels of severity across different patient groups.
Novel V-shaped kiss flap harvest technique for the forearm free flap in soft tissue reconstruction
Authors: Zhao Wenquan , Zhu Wenyuan , Yu Dan , Zhu Huiyong , Liu Jianhua , Ni Youkang
Published: April 2023

Introduction

Radial forearm flap (RFF) is widely used in oral reconstruction. However, the donor-site defect remains the main limit. In this paper, V-shaped kiss RFF (VRFF) is described as a novel technique to improve aesthetics and function of it. A retrospective study was conducted to introduce VRFF and evaluate its effect and safety.

Methods

A total of 21 patients who underwent VRFF for oral reconstruction, and 23 patients who underwent conventional RFF from February 2016 to April 2018 were included in this study. Direct comparisons were made on patient’s subjective evaluation of postoperative hand function and degree of scarring and objective donor-site function assessment including range of wrist movements and grip strength before and after surgery between the two groups.

Results

No skin grafts were used in the VRFF group, and 20 of 21 patients achieved primary healing at donor site, while all patients from the RFF group had skin grafts. And 18 of 23 patients achieved primary healing. The postoperative scar score of donor site in the VRFF group was significantly higher than that in the RFF group (3.4 vs 2.8, P = 0.035). There were no significant differences in other subjective evaluation and donor-site morbidity and hand function assessment.

Conclusion

VRFF is able to provide a new and simple method to close donor-site defect and realize a better healing in donor site.
Clinicopathological characteristics, local treatment, and prognostic factors in IE/IIE primary breast lymphoma: a retrospective study of 67 patients
Authors: Feng Ruigang , Huang Wenwen , Chen Lixuan , Min Jie , Shu Wenjun , Yu Yue , Wang Xin , Cao Xuchen , Liu Bowen
Published: April 2023

Introduction

Primary breast lymphoma (PBL) is a rare disease, treatment of which excerpts does not reach a consensus. This retrospective study was conducted to analyze clinical features and survival outcomes of different therapeutic methods.

Materials and methods

Records of 67 patients with stage IE/IIE primary breast lymphoma were reviewed from the medical record system. Survival information was gathered by searching the outpatient system. Clinicopathological characteristics were compared by chi-squared or Fisher’s exact tests. A comparison of survival curves was performed by log-rank tests. The Cox proportional hazard model was applied for multivariate analysis.

Results

At the median follow-up time of 65.23 months (range, 9–150 months), there were 27 (40.3%) relapses, 28 (41.8%) distant metastases, and 21 (31.3%) deaths. The 5-year progression-free survival (PFS) and overall survival (OS) were 52.1% and 72.4%. Pathological types (DLBCL vs. non-DLBCL, p = 0.001) and rituximab use (p < 0.001) were statistically associated with longer PFS in patients with PBL. Nodal sites involved and radiotherapy administration were significant predictors for 5-year OS. Multivariate analysis suggested that nodal sites involved (p = 0.005) and radiotherapy administration (p < 0.003) were independent prognostic factors for OS in patients with PBL (p < 0.05). Radical surgery was not an independent factor for patients with PBL.

Conclusions

Radiotherapy improved the survival of patients with PBL. Radical mastectomy offered no additional benefit in the treatment of PBL.
SARS-CoV-2 before and after Omicron: two different viruses and two different diseases?
Authors: Gili Renata , Burioni Roberto
Published: April 2023

For the first time in the history of medicine, it has been possible to describe—after a spillover—the evolution of a new human virus spreading in a non-immune population. This allowed not only to observe the subsequent emersion of variants endowed with features providing the virus with an evolutionary advantage, but also the shift of the pathways of virus replication and the acquisition of immunoevasive features. These characteristics had a remarkable influence on the diffusion of the SARS-CoV-2 and on the clinical presentation and prognosis of COVID-19, aspects that are described and commented in this review.
RETRACTED ARTICLE: Palmitoyl transferases act as novel drug targets for pancreatic cancer
Authors: Lin Zhiqing , Lv Ziru , Liu Xin , Huang Keke
Published: April 2023

Background

Pancreatic adenocarcinoma (PAAD) is one of the most leading causes of cancer-related death across the world with the limited efficiency and response rate of immunotherapy. Protein S-palmitoylation, a powerful post-translational lipid modification, is well-known to regulate the stability and cellular distribution of cancer-related proteins, which is mediated by a family of 23 palmitoyl transferases, namely zinc finger Asp-His-His-Cys-type (ZDHHC). However, whether palmitoyl transferases can determine tumor progression and the efficacy of immunotherapy in PAAD remains unknown.

Methods

Bioinformatics methods were used to identify differential ZDHHCs expression in PAAD. A systematic pan-cancer analysis was conducted to assess the immunological role of ZDHHC3 using RNA sequencing data from The Cancer Genome Atlas database. In vivo Panc 02 subcutaneous tumor model validated the anti-tumor effect of knockdown of ZDHHC3 or intraperitoneal injection of 2-bromopalmitate (2-BP), a typical broad-spectrum palmitoyl transferases inhibitor. Furthermore, we explored therapeutic strategies with combinations of 2-BP with PD-1/PD-L1-targeted immunotherapy in C57BL/6 mice bearing syngeneic Panc 02 pancreatic tumors.

Results

ZDHHC enzymes were associated with distinct prognostic values of pancreatic cancer. We identified that ZDHHC3 expression promotes an immunosuppressive tumor microenvironment in PAAD. 2-BP suppressed pancreatic-tumor cell viability and tumor sphere-forming activities, as well as increased cell apoptosis in vitro, without affecting normal human pancreatic ductal epithelial cells. Furthermore, genetic inactivation of ZDHHC3 or intraperitoneal injection of 2-BP impeded tumor progression in Panc 02 pancreatic tumors with enhanced anti-tumor immunity. 2-BP treatment significantly enhanced the therapeutic efficacy of PD-1/PD-L1 inhibitors in Panc 02 pancreatic tumors.

Conclusion

This study revealed some ZDHHC enzyme genes for predicting the prognosis of pancreatic cancer, and demonstrated that ZDHHC3 plays a critical oncogenic role in pancreatic cancer progression, highlighting its potential as an immunotherapeutic target of pancreatic cancer. In addition, combination therapy of 2-BP and PD-1/PD-L1 achieved synergic therapy effects in a mouse model of pancreatic cancer.
Thymic function and survival at advance ages in nursing home residents from Southern Italy
Authors: Paparazzo Ersilia , Geracitano Silvana , Lagani Vincenzo , Citrigno Luigi , Bartolomeo Denise , Aceto Mirella Aurora , Bruno Francesco , Maletta Raffaele , Passarino Giuseppe , Montesanto Alberto
Published: April 2023

Background

Immunosenescence is a complex process characterized by an age-related remodelling of immune system. The prominent effects of the immunosenescence process is the thymic involution and, consequently, the decreased numbers and functions of T cells. Since thymic involution results in a collapse of the T-cell receptor (TCR) repertoire, a reliable biomarker of its activity is represented by the quantification of signal joint T-cell receptor rearrangement excision circles (sjTRECs) levels. Although it is reasonable to think that thymic function could play a crucial role on elderly survival, only a few studies investigated the relationship between an accurate measurement of human thymic function and survival at old ages.

Methods and findings

By quantifying the amount sjTRECs by real-time polymerase chain reaction (PCR), the decrease in thymic output in 241 nursing home residents from Calabria (Southern Italy) was evaluated to investigate the relationship between thymic function and survival at old ages. We found that low sjTREC levels were associated with a significant increased risk of mortality at older ages. Nursing home residents with lower sjTREC exhibit a near 2-fold increase in mortality risk compared to those with sjTREC levels in a normal range.

Conclusion

Thymic function failure is an independent predictor of mortality among elderly nursing home residents. sjTREC represents a biomarker of effective ageing as its blood levels could anticipate individuals at high risk of negative health outcomes. The identification of these subjects is crucial to manage older people’s immune function and resilience, such as, for instance, to plan more efficient vaccinal campaigns in older populations.
A retrospective comparison of double-hooked locking plates versus non-locking plates in minimally invasive percutaneous plate osteosynthesis for the treatment of comminuted distal fibular fractures accompanied by tibial Pilon fractures
Authors: Liu Jun-Hong , Zhang Qiang , Wei Guo-Hua , Liu Liang , Mu Xin , Li Mao-Lin , Wu Zong-De
Published: April 2023

Background

Surgical approach and fixation material are crucial in the treatment of comminuted distal fibular fractures accompanied by tibial Pilon fractures. This study compared the efficacy of double-hooked locking plates and anatomic plates in minimally invasive percutaneous plate osteosynthesis (MIPPO) for the treatment of comminuted distal fibular fractures accompanied by tibial Pilon fractures.

Methods

Clinical data were collected from 96 patients diagnosed with comminuted distal fibular fractures accompanied by tibial Pilon fractures who had undergone MIPPO. Patients in the study group (n = 48) received double-hooked locking plate fixations and the control group (n = 48) received anatomical plate fixations. The operating time, intraoperative bleeding, length of hospital stays, full weight-bearing time, fracture healing time and complication rates in the two groups were compared. The quality of fracture reduction was evaluated using the Burwell–Chamley imaging scoring system; the ankle function was assessed based on the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Score.

Results

Patients in the study group had shorter operating time, less bleeding, significantly shorter hospital stays, and shorter time to full weight-bearing as well as fracture healing compared to the control group (P < 0.05). Additionally, the post-operative complication rates were significantly lower in the study group (6.16% vs. 22.92%) (P < 0.05), but there was no significant difference in the fracture reduction rate between the two groups (P > 0.05). Patients in the study group experienced better ankle recovery than those in the control group (93.75% vs. 75.00%) (P < 0.05).

Conclusion

Double-hooked locking plates have advantages in the treatment of comminuted distal fibular fractures accompanied by tibial Pilon fractures during MIPPO due to their shorter operating time and less intraoperative bleeding, as well as shorter hospital stays, full weight-bearing time and fracture healing time, fewer complications and better ankle recovery. Therefore, double-hooked locking plates are worthy of clinical application.
Temporal transcriptome highlights the involvement of cytokine/JAK/STAT3 signaling pathway in the osteoinduction of BMSCs
Authors: Ru Xiao , Cai Peian , Tan Manli , Zheng Li , Lu Zhenhui , Zhao Jinmin
Published: April 2023

Background

Mesenchymal stem cells (MSCs)-based therapy offers an effective strategy for bone regeneration to solve the clinical orthopedic problems. However, the transcriptional regulation of multiple transitional stages of continuous osteogenesis from MSCs has not been fully characterized.

Methods

Bone marrow mesenchymal stem cells (BMSCs) stimulated with osteogenic induction media were utilized to construct the in vitro osteogenic differentiation model. BMSCs were harvested after induction for 0, 7, 14 and 21 days, respectively, to perform the mRNA-sequencing (mRNA-Seq). The transcription factor networks and common molecules during the osteogenesis were revealed by using the temporal transcriptome. Further verification was performed by the quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence and Western blotting.

Results

It showed that BMSCs could differentiate into osteogenic, and crucial regulator in the MAPK signaling pathway, the PPAR signaling pathway, the Toll-like receptor signaling and the Cytokine/JAK/STAT signaling pathway. PPI protein interaction analysis also suggested that three cytokines are involved in osteogenic differentiation as core genes, including leukemia inhibitory factor (LIF), interleukin-6 (IL6) and colony-stimulating factor 3 (CSF3). The osteogenic process was negatively affected by the inhibition of JAK/STAT3 signaling pathway.

Conclusions

This work might provide new insights in the crucial features of the transcriptional regulation during the osteogenesis, as well as offer important clues about the activity and regulation of the relatively long-activated Cytokine/JAK/STAT3 signaling pathway in osteoinduction of BMSCs.
Autologous myocutaneous flap implantation for chronic refractory chest wall sinus with infection: a case report
Authors: Wang Lei , Liu Zhijun , He Zhongliang , Zhang Chun
Published: April 2023

Background

Chest wall sinus with infection is a refractory disease caused by a variety of susceptible factors, and the treatment is still challenging. For clinically complex cases, although there are various surgical methods to choose from, it is still very difficult to achieve clinical cure, especially for patients with older age and many underlying diseases. Complete resection of chest wall sinus and application of repair and reconstruction technology may bring hope to refractory cases.

Case presentation

Herein, we report a case of a 67 year-old woman who had undergone breast cancer surgery and a history of multiple cycles of radiotherapy and chemotherapy. One year ago, she had a fistula in the left chest wall with yellow purulent fluid. After admission to our hospital, chest computed tomography (CT) showed the formation of the left chest wall sinus, accompanied by high-density images of the left clavicle, part of the ribs and part of the sternu. According to the patient's symptoms, signs and imaging examination, we preliminarily diagnosed the patient as chest wall sinus with infection and chronic osteomyelitis. Therefore, in the first-stage operation, the patient underwent left chest wall sinus resection, left partial rib resection, left partial clavicular resection and left partial sternal resection, After surgery, the wound surface was changed with gauze dressing with sensitive antibiotic solution every day until the wound surface was clean and new granulation was formed. In the second-stage operation, the wound surface was appropriately expanded, and the pedicled latissimus dorsi myocutaneous flap was transferred to the chest wall defect. Finally, the skin paddle was sutured without tension to the normal skin around the chest, and two drainage tubes were placed. Anti-infection, anti-spasm, anti-coagulation and other treatments were given after operation, and the survival of myocutaneous flap, wound healing and sinus disappearance were observed.

Conclusion

The application of pedicled latissimus dorsi myocutaneous flap in the treatment of intractable chronic chest wall sinus is an effective method. It does not change the shape of the thorax. The clinical effect is satisfactory in the near and medium term, which is worthy of clinical promotion.
Computed tomography-guided lung biopsy with rapid on-site evaluation for diagnosis of lung lesions: a meta-analysis
Authors: Wu Di , Liu Yue-Yue , Wang Tao , Huang Ya-Yong , Xia Ping
Published: April 2023

Background

Lung biopsy (LB) procedures performed with computed tomography (CT guidance can enable the reliable diagnosis of lung lesions. These diagnostic efforts can be further expedited through a rapid on-site evaluation (ROSE) approach, allowing for the rapid assessment of collected tissue samples to gauge the adequacy of these samples, their features, and associated cytomorphological characteristics. The present analysis was developed to examine the safety and efficacy of CT-guided LB with ROSE as a means of diagnosing lung lesions.

Methods

Studies published as of July 31, 2022 in the PubMed, Embase, and Wanfang databases were identified for this meta-analysis. Diagnostic accuracy was the primary endpoint, while secondary endpoints included the operative duration, the number of punctures, and rates of lung hemorrhage, pneumothorax, and secondary LB.

Results

This meta-analysis included 6 total studies. Relative to CT alone, CT with ROSE was associated with a significant increase in diagnostic accuracy (P < 0.00001). In contrast, there were no significant differences between these two groups with respect to the operative duration (P = 0.86), the number of punctures (P = 0.60), or the rates of pneumothorax (P = 0.82) or lung hemorrhage (P = 0.81). Pooled secondary LB rates were significantly lower for patients that underwent CT with ROSE relative to patients in the CT only group (P = 0.0008). Significant heterogeneity was detected for the operative duration (I2 = 94%) and number of punctures (I2 = 98%) endpoints, while no publication bias was detected for any study endpoints.

Conclusions

These results suggest that ROSE may contribute to significant improvements in the diagnostic accuracy of CT-guided LB without contributing to higher rates of complications.
Post-pneumonectomy syndrome: a systematic review of the current evidence and treatment options
Authors: Christodoulides Natasha , Fitzmaurice Gerard J. , Bukowska Irmina , O’Rhaillaigh Eoin , Toale Conor , Griffin Michael , Redmond Karen C.
Published: April 2023

Objectives

Post-pneumonectomy syndrome (PPS) is rare and predominantly characterised by dynamic airway obstruction due to mediastinal rotation at any time point following pneumonectomy. The objective of this systematic review was to identify the optimal treatment strategy for PPS based on subjective symptomatic relief, objective radiological imaging, and treatment durability.

Methods

A systematic review was performed up to and including February 2022 based on the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” guidelines. All studies that presented the management of symptomatic patients > 16 years of age with radiologically confirmed PPS were included. The primary outcome was the identification of the optimal treatment strategy and the secondary outcome was durability of the treatment. The Oxford Centre for Evidence Based Medicine level was assigned to each study.

Results

A total of 330 papers were identified and reviewed; 41 studies met the inclusion criteria. Data including patient demographics, indication for initial pneumonectomy, presenting symptoms, management approach, outcomes, and follow-up were assessed and analysed. Management approaches were divided into three categories: (a) mediastinal repositioning using implant prostheses; (b) endobronchial stenting; (c) other corrective procedures. One hundred and four patients were identified in total and of those, 87 underwent mediastinal repositioning with insertion of a prosthetic implant. Complications included over- or under-filling of the prosthesis (8.5%) and implant leakage (8.9%).

Conclusion

Management of PPS using a prosthetic implant to reposition the mediastinum is the treatment of choice. Key adjuncts to optimise surgical approach and minimise complications include pre-operative CT volumetric analysis to guide implant size and intra-operative transoesophageal echocardiography to guide mediastinal repositioning.