bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimum tacrolimus trough levels for enhanced graft survival and safety in kidney transplantation: a retrospective multicenter real-world evidence study
Authors: Han Ahram , Jo Ae Jeong , Kwon Hyunwook , Kim Young Hoon , Lee Juhan , Huh Kyu Ha , Lee Kyo Won , Park Jae Berm , Jang Eunju , Park Sun Cheol , Lee Joongyub , Lee Jeongyun , Kim Younghye , Soliman Mohamed , Min Sangil
Published: June 2024

Background:

The current study aimed to determine the optimal tacrolimus trough levels for balancing graft survival and patient safety following kidney transplantation.

Materials and methods:

We conducted a retrospective cohort study involving 11 868 kidney transplant recipients from five medical centers. The association between tacrolimus exposures (periodic mean trough level, coefficient of variability, time in therapeutic range) and composite allograft outcome (de novo donor-specific antibody, biopsy-proven rejection, kidney dysfunction, and graft failure), as well as safety outcomes (severe infection, cardiovascular events, malignancy, and mortality) were assessed. Data were sourced from Clinical Data Warehouses and analyzed using advanced statistical methods, including Cox marginal structural models with inverse probability treatment weighting.

Results:

Tacrolimus levels of 5.0–7.9 ng/ml and 5.0–6.9 ng/ml during the 2–12 month and 12–72 month post-transplantation periods, respectively, were associated with reduced risks of composite allograft outcomes. During the first post-transplant year, the adjusted hazard ratios (aHR) for composite allograft outcomes were 0.69 (95% CI 0.55–0.85, P<0.001) for 5.0–5.9 ng/ml; 0.81 (95% CI 0.67–0.98, P=0.033) for 6.0–6.9 ng/ml; and 0.73 (95% CI 0.60–0.89, P=0.002) for 7.0–7.9 ng/ml (compared to levels ≥8.0 ng/ml). For the 6-year composite outcomes, aHRs were 0.68 (95% CI 0.53–0.87, P=0.002) for 5.0–5.9 ng/ml and 0.65 (95% CI 0.50–0.85, P=0.001) for 6.0–6.9 ng/ml. These optimal ranges showed reduced rates of severe infection (6 years), malignancy (6 years), and mortality (1 year).

Conclusion:

This multicenter study provides robust evidence for optimal tacrolimus trough levels during the periods 2–12 and 12–72 months following kidney transplantation.
Application of indocyanine green fluorescence imaging in hepatobiliary surgery
Authors: Zhou Jia , Tan Zhiguo , Sun Bo , Leng Yufang , Liu Sulai
Published: June 2024

Indocyanine green (ICG) is a fluorescent dye with an emission wavelength of about 840 nm, which is selectively absorbed by the liver after intravenous or bile duct injection, and then it is excreted into the intestines through the biliary system. With the rapid development of fluorescence laparoscopy, ICG fluorescence imaging is safe, feasible, and widely used in hepatobiliary surgery. ICG fluorescence imaging is of great significance in precise preoperative and intraoperative localization of liver lesions, real-time visualization of hepatic segmental anatomy, intrahepatic and extrahepatic biliary tract visualization, and liver transplantation. ICG fluorescence imaging facilitates efficient intraoperative hepatobiliary decision-making and improves the safety of minimally invasive hepatobiliary surgery. Advances in imaging systems will increase the use of fluorescence imaging as an intraoperative navigation tool, improving the safety and accuracy of open and laparoscopic/robotic hepatobiliary surgery. Herin, we have reviewed the status of ICG applications in hepatobiliary surgery, aiming to provide new insights for the development of hepatobiliary surgery.
The role of immune cell signatures in the pathogenesis of ovarian-related diseases: a causal inference based on Mendelian randomization
Authors: Lu Yangguang , Yao Yingyu , Zhai Sijia , Ni Feitian , Wang Jingyi , Chen Feng , Zhang Yige , Li Haoyang , Hu Hantao , Zhang Hongzhi , Yu Bohuai , Chen Hongbo , Huang Xianfeng , Ding Weiguo , Lu Di
Published: June 2024

Background:

Immune cells play a pivotal role in maintaining ovarian function. However, the specific contributions of different immune cell phenotypes to the pathogenesis of specific ovarian-related diseases remain poorly understood. The authors aim to investigate the correlation between 731 immunophenotypes and ovarian-related diseases.

Materials and methods:

Utilizing publicly available genetic data, the authors undertook a series of quality control measures to identify instrumental variables associated with exposure. Subsequently, we conducted two-sample Mendelian randomization (MR) using inverse variance weighting to explore the causal relationships between 731 immune cell features and six ovarian-related diseases: ovarian cysts, ovarian dysfunction, premature ovarian failure (POF), polycystic ovary syndrome (PCOS), benign neoplasm of ovary, and malignant neoplasm of ovary at the genetic level. Sensitivity analyses, including leave-one-out and other MR analysis models, were performed. Finally, Bayesian colocalization (COLOC) analysis was employed to identify specific co-localized genes, thereby validating the MR results.

Results:

At the significance level corrected by Bonferroni, four immune phenotypes, including CD25 on IgD- CD38- B cells, were associated with ovarian cysts; four immune phenotypes, including CD39+ CD4+ T cell Absolute Count, were associated with ovarian dysfunction; eight immune phenotypes, including SSC-A on HLA DR+ CD8+ T cells, were associated with POF; five immune phenotypes, including CD20- CD38- B cell Absolute Count, were associated with PCOS; five immune phenotypes, including CD4+ CD8dim T cell Absolute Count, were associated with benign ovarian tumors; and three immune phenotypes, including BAFF-R on IgD- CD38+ B cells, were associated with malignant ovarian tumors. Sensitivity analysis indicated robust results. COLOC analysis identified four immune cell co-localized variants (rs150386792, rs117936291, rs75926368, and rs575687159) with ovarian diseases.

Conclusion:

Our study elucidates the close genetic associations between immune cells and six ovarian-related diseases, thereby providing valuable insights for future research endeavors and clinical applications.
Digital assessment of tertiary lymphoid structures and therapeutic responses in gastric cancer: a multicentric retrospective study
Authors: Chen Yan , Sun Zepang , Yin Junmei , Ahmad M. Usman , Zhou Zixia , Feng Wanying , Yang Fan , Zhou Kangneng , Xie Jingjing , Bie Caiqun , Chen Hongzhuan , Jiang Yuming
Published: June 2024

Background:

Tertiary lymphoid structures (TLSs) are associated with favorable prognosis and enhanced response to anticancer therapy. A digital assessment of TLSs could provide an objective alternative that mitigates variability inherent in manual evaluation. This study aimed to develop and validate a digital gene panel based on biological prior knowledge for assessment of TLSs, and further investigate its associations with survival and multiple anticancer therapies.

Materials and methods:

The present study involved 1704 patients with gastric cancer from seven cancer centers. TLSs were identified morphologically through hematoxylin-and-eosin staining. The authors further developed a digital score based on targeted gene expression profiling to assess TLSs status, recorded as gene signature of tertiary lymphoid structures (gsTLS). For enhanced interpretability, we employed the SHapley Additive exPlanation (SHAP) analysis to elucidate its contribution to the prediction. The authors next evaluated the signature’s associations with prognosis, and investigated its predictive accuracy for multiple anticancer therapies, including adjuvant chemotherapy and immunotherapy.

Results:

The gsTLS panel with nine gene features achieved high accuracies in predicting TLSs status in the training, internal, and external validation cohorts (area under the curve, range: 0.729–0.791). In multivariable analysis, gsTLS remained an independent predictor of disease-free and overall survival (hazard ratio, range: 0.346–0.743, all P<0.05) after adjusting for other clinicopathological variables. SHAP analysis highlighted gsTLS as the strongest predictor of TLSs status compared with clinical features. Importantly, patients with high gsTLS (but not those with low gsTLS) exhibited substantial benefits from adjuvant chemotherapy (P<0.05). Furthermore, the authors found that the objective response rate to antiprogrammed cell death protein 1 (anti-PD-1) immunotherapy was significantly higher in the high-gsTLS group (40.7%) versus the low-gsTLS group (5.6%, P=0.036), and the diagnosis was independent from Epstein–Barr virus, tumor mutation burden, and programmed cell death-ligand 1 (PD-L1) expression.

Conclusion:

The gsTLS digital panel enables accurate assessment of TLSs status, and provides information regarding prognosis and responses to multiple therapies for gastric cancer.
Early admission is better–the time to admission (TTA) is associated with one-year mortality in hip fracture
Authors: Zhang Bin-Fei , Xu Shuai-Liang , Yang Zhi , Xu Peng
Published: June 2024

Objective:

This study evaluated the probable association between time to admission (TTA) and 1-year mortality in geriatric hip fractures.

Methods:

Older adult patients with hip fractures were screened between January 2015 and September 2019. The demographic and clinical characteristics of the patients were collected at the largest trauma center in Northwest China. TTA can be obtained from the medical record system and converted into a categorical variable. Multivariate binary logistic regression and generalized additive model were used to identify the linear and nonlinear association between TTA and 1-year mortality. Analyses were performed using EmpowerStats and the R software.

Results:

Two thousand three hundred and sixty-one patients who met the criteria were finally included. There were 1618 (68.53%) female and 743 (31.47%) male patients. All patients were divided into three groups according to their TTA. The proportions of patients with low (≤6 h), middle (>6, ≤24 h), and high (>24 h) waiting times were 995, 654, and 712, respectively, and the corresponding 1-year mortality rates were 62 (6.23%), 72 (11.01%), and 82 (11.52%). We found a curve relationship between TTA and 1-year mortality by two-piecewise linear regression, and 9 h was an inflection point. When TTA was less than 9 h, the 1-year mortality of patients increased by 9% for every 1 h increase in TTA (OR=1.09, 95% CI: 1.03–1.16; P<0.01). When TTA was greater than 9 h, the mortality of patients no longer increased with the rise of TTA (OR=1.00, 95% CI: 1.00–1.00; P=0.26).

Conclusion:

TTA is a probable predictor of 1-year mortality. The authors found that 9 h was an inflection point. If TTA is less than 9 h, the mortality rate of patients will be lower. If it takes more than 9 h, the mortality will be higher. Therefore, the elderly who are found to have possible hip fractures should be admitted to the hospital as soon as possible.
Factor XIII deficiency leading to a life-threatening intracranial hemorrhage in a young female: a case report
Authors: Poombal FNU , Fayyaz Hafiz Noor Ullah , Saeed Hira , Adhikari Sugat
Published: June 2024

Introduction and importance:

Factor XIII (FXIII) deficiency, a rare coagulation disorder resulting from F13A1 gene mutations, can lead to severe bleeding episodes, especially in infants. The authors’ case study featuring a 16-year-old female with a history of this deficiency revealed intracranial hemorrhage necessitating immediate medical intervention. The text emphasizes the importance of understanding the epidemiology and genetics of FXIII deficiency, as well as the challenges in diagnosis and management.

Case presentation:

A 16-year-old female with FXIII deficiency presented to the Emergency Department (ER) after a fall, experiencing weakness on her right side, headache, seizures, and altered consciousness. Neurological examination showed weakness and increased tone on the right side of the body. Computed tomography (CT) scan revealed an intracranial subdural hemorrhage overlying the superior parietal lobe. Treatment included IV fluids, sodium valproate, antibiotics, fresh frozen plasma, and mannitol. Serial neurological assessments were normal, and the patient remained stable. MRI later confirmed hemorrhage. Upon discharge, she was prescribed medication and physiotherapy, leading to significant improvement at the 6-month follow-up.

Clinical discussion:

The prevalence of FXIII deficiency, a rare disorder, is higher in populations with consanguineous marriages, particularly in regions like Pakistan, India, Tunisia, Finland, and Iran due to specific genetic mutations. Diagnosis involves thorough evaluation and specific lab tests, with varied clinical symptoms including prolonged bleeding, especially in newborns. FXIII deficiency can also develop in association with conditions like hepatic failure and leukemia, complicating diagnosis. Treatment options include blood products and recombinant FXIII, with management of intracranial bleeding requiring a multidisciplinary approach.

Conclusion:

The case underscores the critical need for early identification and specialized care for individuals with FXIII deficiency to mitigate life-threatening complications like intracranial hemorrhage, promoting tailored treatment approaches and improved patient outcomes.
Impact of Legal Guardian Absence on Research Enrollment in the PICU*
Authors: Armstrong Jennifer , Gibson Jess , O’Hearn Katie , Martin Dori-Ann , Assaf Maysaa , Menon Kusum
Published: June 2024

OBJECTIVES:

To identify the frequency of which a legal guardian is at the bedside of children admitted to the PICU that are eligible for research studies.

DESIGN:

A prospective, observational study.

SETTING:

Three tertiary Canadian PICUs.

PATIENTS:

Two hundred one patients were admitted to the PICU between September 2021 and March 2023 (site 1), from March 2019 to March 2020 and March 2022 to March 2023 (site 2), and from March 2019 to March 2020 and July 2020 to November 2021 (site 3).

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

At each center, the duration of consent encounters was recorded for patients eligible for research by documenting the length of each attempt (min). The frequency of parental presence at bedside and the ability for a guardian to make a decision were also recorded. Thirty-five percent of patients eligible for research did not have a legal guardian at the bedside on the first attempted consent encounter. Twenty-three percent of approached patients were not enrolled due to an inability for a consent decision to be made by the child’s legal guardian or an inability to contact the guardian before discharge.

CONCLUSIONS:

The absence of legal guardians in the PICU poses a barrier to the enrollment of critically ill children in pertinent research studies and suggests that a model of deferred consent or implied consent would aid in the future of critical care research.
Brief Report: Subsequent Pregnancies in the IMPAACT 2010/VESTED Trial: High Rate of Adverse Outcomes in Women Living With HIV
Authors: Fairlie Lee , Brummel Sean , Ziemba Lauren , Coletti Anne , Chinula Lameck , Shapiro Roger , Stringer Jeffrey , Malonga Grace , Browning Renee , Chakhtoura Nahida , Mmbaga Blandina Theophil , Mhembere Tsungai P. , Omoz-Oarhe Ayotunde , Nagaddya Beatrice , Naidoo Megeshinee , Hoffman Risa M. , Lockman Shahin ,   for the IMPAACT 2010/VESTED Study Team
Published: June 2024

Introduction:

Women with HIV (WHIV) have higher risks of adverse pregnancy outcomes, particularly in the absence of antiretroviral treatment (ART), and timing of ART may impact risk.

Methods:

In the International Maternal Pediatric Adolescent AIDS Clinical Trials 2010/VESTED study, 643 pregnant WHIV in 9 countries were randomized in a 1:1:1 ratio to initiate ART: dolutegravir (DTG)+emtricitabine (FTC)/tenofovir alafenamide (TAF), DTG+FTC/tenofovir disoproxil fumarate (TDF), or efavirenz (EFV)/FTC/TDF. We describe adverse pregnancy outcomes in women with a subsequent pregnancy during 50 weeks of postpartum follow-up: spontaneous abortion (<20 weeks), stillbirth (≥20 weeks), preterm delivery (<37 weeks), and small for gestational age.

Results:

Of 643 women, 19 (3%) had 20 subsequent pregnancies while receiving ART at conception: DTG/FTC/TAF (3), DTG/FTC/TDF (2), EFV/FTC or lamivudine (3TC)/TDF (12), EFV/abacavir/3 TC (1), and no ART (1). Four spontaneous abortions, 3 stillbirths, and 1 induced abortion occurred. Three (25%) of 12 liveborn infants were preterm (24, 26, and 36 weeks of gestation). Only 12 subsequent pregnancies (60%) resulted in live birth, and at least 1 adverse pregnancy outcome occurred in 11 of 19 (58%) (induced abortion excluded). Of 7 women who experienced spontaneous abortion/stillbirth in the subsequent pregnancy, 4 experienced a stillbirth and 1 a neonatal death as outcomes of their earlier index pregnancy. No congenital anomalies were reported.

Conclusions:

Adverse pregnancy outcomes were common in this cohort of WHIV who conceived on ART shortly after an index pregnancy, 35% ended in stillbirth or spontaneous abortion. The majority of fetal losses occurred in women with recent prior pregnancy loss. Data from larger cohorts of WHIV conceiving on ART and surveillance are needed to elucidate rates and predictors of adverse pregnancy outcome.
Relationships Between Hepatic Steatosis and Frailty Differ by HIV Serostatus
Authors: Debroy Paula , Barrett Benjamin W. , Erlandson Kristine M. , Budoff Matthew , Brown Todd T. , Price Jennifer C. , Post Wendy S. , Stosor Valentina , Skavarca Carling , D'Souza Gypsyamber , Lake Jordan E.
Published: June 2024

Background:

Frailty is associated with obesity-related comorbidities, but the relationship with nonalcoholic fatty liver disease (NAFLD) in people with HIV has been incompletely described. Our objective was to assess the associations between NAFLD and frailty.

Methods:

Cross-sectional and longitudinal analysis of men in the Multicenter AIDS Cohort Study. NAFLD was defined as a liver/spleen ratio <1.0 on abdominal computed tomography scans; frailty was defined by the frailty phenotype as having 3 of the following: weakness, slowness, weight loss, exhaustion, and low physical activity.

Results:

Men without (n = 200) and with HIV (n = 292) were included. NAFLD prevalence was 21% vs 16% and frailty 12% vs 17%, respectively. Among men with NAFLD, frailty was more prevalent in men without HIV (21% vs 11%). In multivariate analysis, NAFLD was significantly associated with frailty after controlling for significant variables. Men without HIV and NAFLD had 2.6 times higher probability [95% confidence interval (CI): 1.2– to 5.7] of frailty relative to men with neither HIV nor NAFLD. This association was not seen in men with HIV. The probability of frailty was higher among men without HIV with NAFLD (27% vs 10% in men without NAFLD) but lower among men with HIV with NAFLD (14% vs 19% in men without NAFLD). No significant relationships were found in longitudinal analyses.

Conclusions:

NAFLD was independently associated with frailty among men without HIV but not men with HIV, despite increased prevalence of frailty among men with HIV. The mechanisms of the muscle–liver–adipose tissue axis underlying NAFLD might differ by HIV serostatus.
Comparing Different Donor Sites After Vascularized Lymph Node Transfer to the Lymphedematous Upper Limb
Authors: Braizat Omar , Jarrar Salma , El-Debs Mohammed , Al-Adwan Mohammad Abu Orabi , Syaj Sebawe , Abuzanouneh Faris , Mohammed Mazin , Mohammedali Shiyas , Quazi Sohail Jamiluddin , Muneer Mohammed
Published: June 2024

Background

Vascularized lymph node transfer (VLNT) involves the microvascular transplantation of functional lymph nodes from a donor site into a limb affected by lymphedema to restore the normal flow of lymphatic fluid. Despite the increasing clinical experience with VLNT, there remains insufficient data to support its routine use in clinical practice. Here, we aim to evaluate the effectiveness and safety of VLNTs for upper limb lymphedema and compare clinical outcomes when using different donor sites.

Methods

We carried out a systematic search of the literature through PubMed and Scopus databases for studies on VLNT for upper limb lymphedema. Primary and secondary outcomes included circumference reduction rate (CRR) and infection reduction rate by postoperative cellulitis episodes for the efficacy and safety of VLNT. Pooled analysis was performed using the inverse variance weighting meta-analysis of single means using the meta package in R software. Subgroup analyses were performed for donor and recipient sites, age groups, follow-ups, and symptom durations. Quality assessment was performed using the Newcastle-Ottawa Scale for nonrandomized studies.

Results

A total of 1089 studies were retrieved from the literature, and 15 studies with 448 upper limb lymphedema patients who underwent VLNT were included after eligibility assessment. The mean CRR was 34.6 (18.8) and the mean postoperative cellulitis episodes per year was 0.71 (0.7). The pooled analysis of CRR was 28.4% (95% confidence interval, 19.7–41.1) and postoperative cellulitis episodes showed a mean of 0.59 (95% confidence interval, 0.36–0.95) using the random-effect model. Subgroup analyses showed significant group differences in recipient site for CRR and postoperative cellulitis episodes with the wrist comprising the highest weights, and patients younger than 50 years showing a lower postoperative infection.

Conclusions

Vascularized lymph node transfer using gastroepiploic flaps at the wrists has shown a significant difference in reductions of limb circumference and cellulitis episodes in upper limb lymphedema patients when compared with other donor sites. However, further prospective studies are needed to consolidate this finding.
Patient-Reported Outcomes and Complication Profiles of Implant-Based Breast Reconstruction in Patients With Postmastectomy Radiation Therapy
Authors: Liu Jian , Chen Cong , Chen Honggang , Xiang Aizhai , Zheng Ruzhen , Hu Shufang , Guo Jufeng , Qu Li , Zhou Jun , Wu Jiong
Published: June 2024

Objective

This study aims to investigate the patient-reported outcomes (PROs) and complications of distinct implant-based breast reconstruction modality for patients with postmastectomy radiation therapy (PMRT).

Methods

A retrospective review was conducted on breast cancer patients with stage II-III disease who performed implant-based breast reconstruction following with PMRT between September 2016 and April 2022. The patients were categorized into two matched groups: (1) patients receiving prepectoral breast reconstruction (PBR) or (2) subpectoral breast reconstruction (SBR) followed by PMRT. Following reconstruction, the patients were further compared for PMRT with the tissue expander (PMRT-TE) versus PMRT with permanent implant (PMRT-PI). PROs were measured with BREAST-Q questionnaire. Early and late complications were recorded and analyzed.

Results

A total of 55 eligible patients were recruited. Patients who underwent PBR reported significantly higher satisfaction with breasts scores (P = 0.003) compared with the SBR group. The PMRT-TE group had higher satisfaction with breasts (P = 0.001) but lower physical well-being (P = 0.029) scores compared with PMRT-PI group. Moreover, patients in SBR cohort had a higher risk of capsular contracture (Baker grade III or IV) (20.5% vs 6.3%) and implant dislocation (48.7% vs 12.5%) than patients in PBR cohort. Patients in PMRT-PI group had a slightly higher rate of capsular contracture (Baker grade III or IV) than PMRT-TE group (20.8% vs 12.9%).

Conclusions

PBR was associated with lower rates of late complications, especially for implant dislocation, and higher satisfaction with breasts scores compared to SBR. In addition, compared to PMRT-TE with PMRT-PI, patients in PMRT-TE cohort reported superior PROs of satisfaction with breasts.
A World Update of Progress in Lower Extremity Transplantation
Authors: Kodali Naga Anvesh , Janarthanan Ramu , Sazoglu Bedreddin , Demir Zeynep , Dirican Omer , Zor Fatih , Kulahci Yalcin , Gorantla Vijay S.
Published: June 2024

The field of vascularized composite allotransplantation (VCA) is the new frontier of solid organ transplantation (SOT). VCA spans life-enhancing/life-changing procedures such as upper extremity, craniofacial (including eye), laryngeal, tracheal, abdominal wall, penis, and lower extremity transplants. VCAs such as uterus transplants are life giving unlike any other SOT. Of all VCAs that have shown successful intermediate- to long-term graft survival with functional and immunologic outcomes, lower extremity VCAs have remained largely underexplored. Lower extremity transplantation (LET) can offer patients with improved function compared to the use of conventional prostheses, reducing concerns of phantom limb pain and stump complications, and offer an option for eligible amputees that either fail prosthetic rehabilitation or do not adapt to prosthetics. Nevertheless, these benefits must be carefully weighed against the risks of VCA, which are not trivial, including the adverse effects of lifelong immunosuppression, extremely challenging perioperative care, and delayed nerve regeneration. There have been 5 lower extremity transplants to date, ranging from unilateral or bilateral to quadrimembral, progressively increasing in risk that resulted in fatalities in 3 of the 5 cases, emphasizing the inherent risks. The advantages of LET over prosthetics must be carefully weighed, demanding rigorous candidate selection for optimal outcomes.
Local Management for Diabetic Foot Ulcers
Authors: Qian Hu , Jian Yang , Chu Xiangyuan , Wang Yuanliang , Liu Zhu , Zhang Neng , Deng Chenliang , Shi Xiuquan , Wei Zairong
Published: June 2024

Objective:

This study evaluated the efficacy of various local management strategies for diabetic foot ulcers (DFUs).

Background:

Several surgical and nonsurgical local interventional approaches are available for the treatment of DFUs. The comparative effectiveness of different treatments is unknown, and it remains unclear which approach is the optimal choice for DFU treatment due to limited direct comparisons.

Methods:

We did a systematic review and meta-analysis to select the optimal approach to DFU's local management. We searched Medline, Embase, Web of Science, and ClinicalTrials.gov from inception to September 1, 2023, to identify relevant randomized controlled trials. We analyzed data by pairwise meta-analyses with a random-effects model. A network meta-analysis using the surface under the cumulative ranking curve was performed to evaluate the comparative efficacy of different interventional approaches in the early (within 12 wk) and late stages (over 12 wk).

Results:

In all, 141 randomized controlled trials involving 14076 patients and exploring 14 interventional strategies were eligible for inclusion. Most studies (102/141) had at least 1 risk-of-bias dimension. Good consistency was observed during the analysis. Local pairwise comparisons demonstrated obvious differences in the early-stage healing rate and early-stage and late-stage healing times, while no significant difference in the late-stage healing rate or adverse events were noted. surface under the cumulative ranking curves identified the standard of care (SOC) + decellularized dressing (DD), off-loading (OL), and autogenous graft (AG) as the 3 most effective interventions within 12 weeks for both healing rate (97%, mean rank: 1.4; 90%, mean rank: 2.3; 80.8%, mean rank: 3.5, respectively) and healing time (96.7%, mean rank: 1.4; 83.0%, mean rank: 3.0; 76.8%, mean rank: 3.8, respectively). After 12 weeks, local drug therapy (LDT) (89.5%, mean rank: 2.4) and OL (82.4%, mean rank: 3.3) ranked the highest for healing rate, and OL (100.0%, mean rank: 1.0) for healing time. With respect to adverse events, moderate and high risks were detected in the SOC + DD (53.7%, mean rank: 7.0) and OL (24.4%, mean rank: 10.8) groups, respectively.

Conclusion:

The findings suggest that OL provided considerable benefits for DFU healing in both the early and late stages, but the high risk of adverse events warrants caution. SOC+DD may be the preferred option in the early stages, with an acceptable risk of adverse events.
Decoding the Clavien-Dindo Classification
Authors: Staubli Sebastian Manuel , Walker Harriet Louise , Saner Fuat , Salinas Camila Hidalgo , Broering Dieter Clemens , Malagò Massimo , Spiro Michael , Raptis Dimitri Aristotle ,   the HeALgroup.AI
Published: June 2024

Objective:

To assess ChatGPT’s capability of grading postoperative complications using the Clavien-Dindo classification (CDC) via artificial intelligence (AI) with natural language processing.

Background:

The CDC standardizes the grading of postoperative complications. However, consistent and precise application in dynamic clinical settings is challenging. AI offers a potential solution for efficient automated grading.

Methods:

ChatGPT’s accuracy in defining the CDC, generating clinical examples, grading complications from existing scenarios, and interpreting complications from fictional as well as real world clinical summaries were tested.

Results:

ChatGPT 4 precisely mirrored the CDC, outperforming version 3.5. In generating clinical examples, ChatGPT 4 showcased 99% agreement with minor errors in urinary catheterization. For single complications, it achieved 97% accuracy. ChatGPT was able to accurately extract, grade, and analyze complications from free-text fictional discharge summaries. It demonstrated near-perfect performance when confronted with real-world discharge summaries: comparison between the human and ChatGPT4 grading showed a κ value of 0.92 (95% CI: 0.82–1) (P<0.001).

Conclusions:

ChatGPT 4 demonstrates promising proficiency and accuracy in applying the CDC. In the future, AI has the potential to become the mainstay tool to accurately capture, extract, and analyze CDC data from clinical data sets.
Examining the Burden of Non-Communicable Diseases among Elderly Individuals Aged 70 and Older in Jordan over Three Decades
Authors: Abdelhaq Aya , Barakat Duaa , Zghoul Renad , Sultan Iyad
Published: June 2024

Background

This study investigates the trends in non-communicable diseases (NCDs) among the elderly population aged 70 and above in Jordan from 1991 to 2022. The elderly Jordanian population was targeted as it has vastly increased over the years, being approximately 6 times higher in 2021 than in 1991. The aim of this study is to provide a comprehensive insight on the burden of NCDs among Jordan’s elderly population .

Methods

Using data extracted from the Global Burden of Disease (GBD), incidence rates, disability-adjusted life years (DALYs), and mortality rates associated with NCDs were analyzed.

Results

The findings of this study reveal a significant increase in the total burden of NCDs over the three decades reaching an absolute DALYs number of above 262,000 by 2021. Elderly females appear to have a slightly higher burden of NCDs when compared to males over the specified time period of 1991 to 2021. Cardiovascular diseases and diabetes were identified as the primary contributors to this increase and seem to have the highest two death rate ranks. However, when compared to global rates Jordan appears to have a 34% lower NCDs burden. The incidence rates appear to be stable with minimal change suggesting that the NCDs incidence has remained relatively constant in Jordan over the past three decades.

Conclusion

This upward trend underscores the escalating public health challenge posed by NCDs in Jordan’s aging population. This study provides a comprehensive overview of the changes in NCD burden and aims to inform healthcare policy and strategic planning to mitigate the impact of NCDs on the elderly in Jordan.
Prediction of future cognitive decline among cognitively unimpaired individuals using measures of soluble phosphorylated tau or tau tangle pathology
Authors: Ossenkoppele Rik , Salvadó Gemma , Janelidze Shorena , Binette Alexa Pichet , Bali Divya , Karlsson Linda , Palmqvist Sebastian , Mattsson-Carlgren Niklas , Stomrud Erik , Therriault Joseph , Rahmouni Nesrine , Rosa-Neto Pedro , Coomans Emma M. , van de Giessen Elsmarieke , van der Flier Wiesje M. , Teunissen Charlotte E. , Jonaitis Erin M. , Johnson Sterling C. ,   PREVENT-AD Research Group, Villeneuve Sylvia , Benzinger Tammie L.S. , Schindler Suzanne E. , Bateman Randall J. , Doecke James D. , Doré Vincent , Feizpour Azadeh , Masters Colin L. , Rowe Christopher , Wiste Heather J. , Petersen Ronald C. , Jack Clifford R. , Hansson Oskar
Published: June 2024

Plasma p-tau217 and Tau-PET are strong prognostic biomarkers in Alzheimer’s disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In this head-to-head comparison study including 9 cohorts and 1534 individuals, we found that plasma p-tau217 and medial temporal lobe Tau-PET signal showed similar associations with cognitive decline on a global cognitive composite test (R2PET=0.32 vs R2PLASMA=0.32, pdifference=0.812) and with progression to mild cognitive impairment (Hazard ratio[HR]PET=1.56[1.43-1.70] vs HRPLASMA=1.63[1.50-1.77], pdifference=0.627). Combined plasma and PET models were superior to the single biomarker models (R2=0.36, p<0.01). Furthermore, sequential selection using plasma p-tau217 and then Tau-PET reduced the number of participants required for a clinical trial by 94%, compared to a 75% reduction when using plasma p-tau217 alone. We conclude that plasma p-tau217 and Tau-PET showed similar performance for predicting future cognitive decline in CU individuals, and their sequential use (i.e., plasma p-tau217 followed by Tau-PET in a subset with high plasma p-tau217) is useful for screening in clinical trials in preclinical AD.
Multidisciplinary clinical assessment and interventions for childhood listening difficulty and auditory processing disorder: Relation between research findings and clinical practice
Authors: Moore David R. , Lin Li , Bhalerao Ritu , Caldwell-Kurtzman Jody , Hunter Lisa L.
Published: June 2024

Purpose

Listening difficulty (LiD), often classified as auditory processing disorder (APD), has been studied in both research and clinic settings. The aim of this study was to examine the predictive relation between these two settings. In our “SICLiD” research study, children with normal audiometry, but caregiver-reported LiD, performed poorly on both listening and cognitive tests. Here we examined results of clinical assessments and interventions for these children in relation to research performance.

Methods

Study setting was a tertiary pediatric hospital. Electronic medical records were reviewed for 64 children aged 6-13 years recruited into a SICLiD LiD group based on a caregiver report (ECLiPS). The review focused on clinical assessments and interventions provided by Audiology, Occupational Therapy, Psychology (Developmental and Behavioral Pediatrics), and Speech-Language Pathology services, prior to study participation. Descriptive statistics on clinical encounters, identified conditions, and interventions were compared with quantitative, standardized performance on research tests. Z-scores were compared for participants with and without each clinical condition using univariate and logistic prediction analyses.

Results

Overall, 24 clinical categories related to LiD, including APD, were identified. Common conditions were attention (32%), language (28%), hearing (18%), anxiety (16%), and autism spectrum (6%) disorders. Performance on research tests varied significantly between providers, conditions, and interventions. Quantitative research data combined with caregiver reports provided reliable predictions of all clinical conditions except APD. Individual test significant correlations were scarce, but included the SCAN composite score, which predicted clinical language and attention difficulties, but not APD diagnoses.

Conclusions

The variety of disciplines, assessments, conditions and interventions revealed here supports previous studies showing that LiD is a multifaceted problem of neurodevelopment. Comparisons between clinical- and research-based assessments suggest a path that prioritizes caregiver reports and selected psychometric tests for screening and diagnostic purposes.
‘The Recommended Deltoid Intramuscular Injection Sites in the Adult Population: A Cadaveric study with an Orthopedic Perspective’
Authors: Charmode Sundip Hemant , Mishra Abhishek Kumar , Mehra Simmi
Published: June 2024

Background

The deltoid is a common site for intramuscular injections, but guidelines for administration lack standardization. Global researchers propose various techniques, and recent study reports indicate a 1.5-15% incidence of nerve palsies due to injections. Our cadaveric study is aimed to standardize the deltoid intramuscular injection sites in the Southeast-Asian population.

Methods

A cadaveric study of a 2-year duration was conducted in the Department of Anatomy in which twelve upper extremity specimens were dissected by the end of the pilot phase. Anthropometric measurements of deltoid muscle along with the distance of underlying neuro-vascular structures like the Axillary nerve and Posterior Circumflex Humeral Artery were measured from neighboring bony landmarks.

Results

In adults, in anatomical position, the mean distances of the Axillary nerve, and Posterior Circumflex Humeral Artery from the mid-acromial point are 8.19 ± 0.616 cm; and 8.66 ± 0.968 cm respectively. The deltoid thickness at 3, 5, and 7 cm from mid-acromial point was observed to be 1.079 ± 0.13 cm (0.5 cm to 1.78 cm), 1.599 ± 0.12 cm (1 cm to 2.96 cm), 1.815 ± 1.0 cm (1.2 cm to 2.5 cm) respectively. The acquired qualitative and quantitative data were tabulated, graphically represented, and statistically analyzed.

Conclusions

The deltoid IMI must be given at or below the level of the midpoint of the deltoid muscle, but never in the upper half. We recommend a site, 4 fingerbreadths / 9cm below the mid-acromion point as the safest site to avoid injury to any underlying neurovascular structures.
Insights from single-strain and mixed culture experiments on the effects of heatwaves on freshwater flagellates
Authors: Boden Lisa , Klagus Chantal , Boenigk Jens
Published: June 2024

The increasing frequency and intensity of heatwaves driven by climate change significantly impact microbial communities in freshwater habitats, particularly eukaryotic microorganisms. Heterotrophic nanoflagellates are important bacterivorous grazers and play a crucial role in aquatic food webs, influencing the morphological and taxonomic structure of bacterial communities. This study investigates the responses of three flagellate taxa to heatwave conditions through single-strain and mixed culture experiments, highlighting the impact of both biotic and abiotic factors on functional redundancy between morphologically similar protist species under thermal stress. Our results indicate that temperature can significantly impact growth and community composition. However, density-dependent factors also had a significant impact. In sum, stabilizing effects due to functional redundancy may be pronounced as long as density-dependent factors play a minor role and can be overshadowed when flagellate abundances increase.
Metabolic connectivity in ageing.
Authors: Deery Hamish , Liang Emma , Siddiqui Navyaan M , Murray Gerard , Voigt Katharina , Di Paolo Robert , Moran Chris , Egan Gary F , Jamadar Sharna D
Published: June 2024

Information transfer across the brain has a high energetic cost and requires the efficient use of glucose. Positron emission tomography (PET) studies have shown that ageing is associated with a decline in regional rates of cerebral glucose metabolism. However, until recently, it has not been possible to measure the timecourse of molecular activity within an individual using PET, preventing the study of metabolic network connectivity across the brain. Here we report the results of the first high temporal resolution functional PET study examining metabolic connectivity and cognitive function in ageing. The metabolic connectomes of 40 younger (mean age 27.9 years; range 20-42) and 46 older (mean 75.8; 60-89) adults were characterised by high connectivity strength in the frontal, temporal, motor, parietal and medial cortices. Ageing was associated with lower global integration of metabolic hub regions, indicating disrupted information transfer across the metabolic network in older adults. In younger adults, a high proportion of glucose was used to support hubs in the frontal regions. Older adults had a smaller energy budget in comparison to younger adults, and older adults used a higher proportion of energy to support mostly posterior hub regions. This difference in the metabolic network topology in older adults was associated with worse cognitive performance. We conclude that ageing is associated with reduced metabolic connectivity, an altered metabolic network topology and a high glucose cost in hub regions. Our results highlight the fundamental role that metabolism plays in supporting information transfer in the brain and the unique insights that metabolic connectivity provides into the ageing brain.
Detection of multiple cardiac abnormalities using Convolution, Positional Encoder and Transformer on 12-lead ECG recordings
Authors: Ford Adam , Lan Jessica , Ng Kyle
Published: June 2024

Objectives: Firstly, we aimed to develop a system capable of detecting multiple cardiac abnormalities simultaneously from 12-lead ECG recordings. Secondly, we tried to improve the detection by analyzing the relationship between imbalanced datasets and optimal classification thresholds. Methods: A novel fusion of Convolution Positional Encoder and Transformer Encoder was used to solve the multi-label classification problem. We used a proper evaluation metric called area under the precision-recall curve (AUPRC) that enabled us to analyze the precision-recall trade-off and find the optimal thresholds. Results: Having outperformed other popular deep networks, the model achieved the highest AUPRC of 0.96 andf1-score of 0.90 on 42511-sample datasets. We also found the negative correlation coefficient of -0.68 between optimal thresholds and the proportion of positive samples. Significance & Conclusion: This study compared the performances of different deep learning architectures on a medical problem and showed the potential of advanced techniques in capturing spatial, temporal features alongside attention mechanisms. It also introduced how to reduce the impact of imbalanced datasets and find optimal classification thresholds.
Fermion-parity qubit in a proximitized double quantum dot
Authors: Geier Max , Souto Rubén Seoane , Schulenborg Jens , Asaad Serwan , Leijnse Martin , Flensberg Karsten
Published: June 2024

Bound states in quantum dots coupled to superconductors can be in a coherent superposition of states with different electron number but with the same fermion parity. Electrostatic gating can tune this superposition to a sweet spot, where the quantum dot has the same mean electric charge independent of its electron-number parity. Here, we propose to encode quantum information in the local fermion parity of two tunnel-coupled quantum dots embedded in a Josephson junction. At the sweet spot, the qubit states have zero charge dipole moment. This protects the qubit from dephasing due to charge noise acting on the potential of each dot, as well as fluctuations of the (weak) interdot tunneling. At weak interdot tunneling, relaxation is suppressed because of disjoint qubit states. However, for strong interdot tunneling the system is protected against noise affecting each quantum dot separately (energy-level noise, dot-superconductor tunneling fluctuations, and hyperfine interactions). Finally, we describe initialization and readout as well as single-qubit and two-qubit gates by pulsing gate voltages.

Published by the American Physical Society
2024
Study of the magnetoelastic effect in nickel and cobalt thin films at GHz range using x-ray microscopy
Authors: Rovirola Marc , Waqas Khaliq M. , Gustafson Travis , Sosa-Barth Fiona , Casals Blai , Hernàndez Joan Manel , Ruiz-Gómez Sandra , Niño Miguel Angel , Aballe Lucía , Hernández-Mínguez Alberto , Foerster Michael , Macià Ferran
Published: June 2024

We use surface acoustic waves of 1 and 3 GHz in hybrid piezoelectric-magnetic systems with either nickel or cobalt as a magnetic layer to generate magnetoacoustic waves and directly image them using stroboscopic x-ray magnetic circular dichroism imaging. Our measurements visualize and quantify the amplitudes of both acoustic and magnetic components of the magnetoacoustic waves, which are generated in the ferromagnetic layer and can propagate over millimeter distances. Additionally, we quantified the magnetoelastic strain component for nickel and cobalt through micromagnetic simulations.

Published by the American Physical Society
2024
Symmetry, topology, and geometry: The many faces of the topological magnetoelectric effect
Authors: Mahon Perry T. , Lei Chao , MacDonald Allan H.
Published: June 2024

A delicate tension complicates the relationship between the topological magnetoelectric effect (TME) in three-dimensional (3D) Z2 topological insulators (TIs) and time-reversal symmetry (TRS). TRS underlies a particular Z2 topological classification of the electronic ground state of crystalline band insulators and the associated quantization of the magnetoelectric response coefficient calculated using bulk linear-response theory but, according to standard symmetry arguments, simultaneously forbids a nonzero magnetoelectric coefficient in any physical finite-size system. This contrast between theories of magnetoelectric response in formal bulk models and in real finite-sized materials originates from the distinct approaches required to introduce notions of (electronic) polarization and orbital magnetization in these fundamentally different environments. In this work we argue for a modified interpretation of the bulk linear-response calculations in nonmagnetic Z2 TIs that is more plainly consistent with TRS and use this interpretation to discuss the effect's observation—still absent over a decade after its prediction. Our analysis is reinforced by microscopic bulk and thin-film calculations carried out using a simplified but still realistic effective model for the well established V2VI3 [V=(Sb,Bi) and VI=(Se,Te)] family of nonmagnetic Z2 TIs. When a uniform dc magnetic field is included in this model, the anomalous n=0 Landau levels (LLs) play the central role, both in thin films and in bulk. In the former case, only the n=0 LL eigenfunctions can support a dipole moment, which vanishes if there are no magnetic surface dopants and is quantized in the thick-film limit if magnetic dopants at the top and bottom surfaces have opposite orientation. In the latter case, the Hamiltonian projected into the

n

=

0

LL subspace is a one-dimensional Su-Schrieffer-Heeger model with ground-state polarization that is quantized in accordance with the bulk linear-response coefficient calculated for (a lattice regularization of) the starting 3D model. Motivated by analytical results, we conjecture a type of microscopic bulk-boundary correspondence: a bulk insulator with (generalized) TRS supports a magnetoelectric coefficient that is purely itinerant (which is generically related to the geometry of the ground state) if and only if magnetic surface dopants are required for the TME to manifest in finite samples thereof. We conclude that in nonmagnetic Z2 TIs the TME is activated by magnetic surface dopants, that the charge-density response to a uniform dc magnetic field is localized at the surface and specified by the configuration of those dopants, and that the TME is qualitatively less robust against disorder than the integer quantum Hall effect.

Published by the American Physical Society
2024