bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Concentration, Efficacy, and Tolerability of Perampanel in Chinese Pediatric Patients with Epilepsy: Real-World Clinical Experience
Authors: Zhao Ting , Li Hong-Jian , Zhang Hui-lan , Feng Ji-Rong , Yu Jing , Feng Jie , Wang Ting-ting , Sun Yan , Yu Lu-Hai
Published: September 2023

Background:

Information on the efficacy and plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy is limited. Therefore, this real-world retrospective study aimed to assess the efficacy, tolerability, and plasma concentration of the maximum dose of PER for epilepsy treatment in Chinese pediatric patients.

Methods:

A total of 107 pediatric patients from 2 hospitals in China were enrolled in this study. The plasma concentration of PER was determined using ultrahigh-performance liquid chromatography. The primary efficacy endpoint was the seizure reduction rate after PER treatment at the last follow-up.

Results:

The response rate to PER therapy was 59.8% (64/107). The authors observed that patients younger than 6 years of age (n = 49) showed a significantly lower concentration-to-dose ratio than patients with ages between 6 and 14 years (n = 58) (2.2 ± 1.7 vs. 3.0 ± 1.8 mcg·mL−1·kg·mg−1, respectively; P < 0.05). Patients who received enzyme-inducing antiseizure medication had significantly lower concentration-to-dose ratios than those who did not receive enzyme-inducing antiseizure medication (EIASM) (2.1 ± 1.8 vs. 3.1 ± 2.0 mcg·mL−1·kg·mg−1, P < 0.05). A total of 37 patients (34.6%) reported treatment adverse events. Patients with somnolence and irritability had a significantly higher PER plasma concentration than the “no treatment-emergent adverse effect” groups (P < 0.05).

Conclusions:

PER is an effective and well-tolerated treatment option for patients with epilepsy. To ensure the clinical efficacy and safety of PER in pediatric patients, it is necessary to monitor its plasma concentrations.
TREATMENT OF INTERMEDIATE UVEITIS-ASSOCIATED RETINAL VASOPROLIFERATIVE TUMORS: A CASE SERIES
Authors: Elnahry Ayman G. , Bellur Sunil , Wiley Henry E. , Nida Sen H. , Kodati Shilpa
Published: September 2023

Purpose:

To report the use of combination intravitreal pharmacotherapy using anti–vascular endothelial growth factor and short- and long-term corticosteroid implants for the treatment of retinal vasoproliferative tumors (VPTs) associated with intermediate uveitis.

Methods:

Retrospective chart review of patients with VPT secondary to idiopathic intermediate uveitis who underwent combination intravitreal pharmacotherapy at a single center was performed. Multimodal imaging including ultrawide field color fundus photography, ultrawide field fluorescein angiography, and optical coherence tomography obtained before and after treatment were reviewed.

Results:

Four eyes of four patients were treated with multiple injections of a combination of aflibercept, dexamethasone, and fluocinolone acetonide implants for VPT associated with intermediate uveitis. All four patients had improvement in visual acuity, intraocular inflammation, central macular thickness, and retinal vascular leakage, as well as regression of the VPT and reduction in lesion leakage on follow-up.

Conclusion:

Combination intravitreal anti–vascular endothelial growth factor and corticosteroid implants may be a useful approach for the treatment of intermediate uveitis-associated VPTs and can lead to both functional and structural improvement.
Postoperative longitudinal refractive changes in children younger than 8 years with ectopia lentis and Marfan syndrome
Authors: Liu Siyuan , Lian Zhangkai , Young Charlotte , Ng Kityee , Zhang Xinyu , Zheng Danying , Jin Guangming
Published: September 2023

Purpose:

To evaluate the postoperative longitudinal refractive changes in children younger than 8 years with ectopia lentis and Marfan syndrome (MFS).

Setting:

Zhongshan ophthalmic center, Guangzhou, China.

Design:

Retrospective cohort study.

Methods:

Medical data of patients diagnosed with ectopia lentis and MFS that underwent surgery younger than 8 years were collected. Refractive errors and ocular biometric parameters were collected preoperatively and at each follow-up visit. Patients were stratified into groups according to age at surgery, and only the eye operated on first was selected. Multivariate analysis was performed to determine the association between refractive shift and potential risk factors.

Results:

In total, 54 eyes of 54 patients were enrolled. The median age at surgery was 6.21 years (interquartile range [IQR], 5.25 to 6.85), and the median follow-up was 2.0 years (IQR, 1.2 to 2.8 years). At age 8 years, patients demonstrated a median myopic shift ranged from −1.75 diopters (D) (IQR, −2.75 to −1.00 D) for the 4-year-old group to −0.13 D (IQR, −0.50 to −0.06 D) for the 7-year-old group. Multivariate analysis showed that greater myopic shift was associated with younger age at surgery (P = .004), male sex (P = .026), and shorter preoperative axis length (P = .005).

Conclusions:

A tendency toward increasing postoperative myopic was demonstrated in children with ectopia lentis and MFS, with the greatest myopic shift in the younger age groups. If the goal is to reach emmetropia by age 8 years, the immediate postoperative hypermetropic targets should be 1.75 D for age 4 years, 1 D for age 5 years, 0.5 D for age 6 years, and 0 to 0.25 D for age 7 years.
Occupational Factors Associated With Workers’ Depression, Anxiety, and General Fatigue
Authors: Kim Ka Young
Published: September 2023

Objective

We aimed to examine occupational factors affecting workers’ mental health.

Methods

Using data from the fifth Korean Working Conditions Survey, 50,158 workers were analyzed. A multiple logistic regression analysis was conducted to analyze the occupational factors.

Results

Sex, age, education level, occupational type, job satisfaction, shift work, and occupational exposure were risk factors for depression, anxiety, and general fatigue. Furthermore, complete application of PPE decreased the risk of depression and anxiety than no application, but partial application of PPE increased the risk of depression and anxiety. Complete and partial application of PPE increased the risk of general fatigue.

Conclusions

This study demonstrated that occupational factors are associated with mental health. This suggests that it is necessary to improve the working environment so that PPE can be applied structurally or systematically to protect against hazardous occupational exposure.
The number of metastatic lymph nodes is more predictive of prognosis than Location-based N stage for Non-small cell lung cancer: a retrospective cohort study
Authors: Xu Long , Si Haojie , Su Hang , Wang Fang , Wu Junqi , She Yunlang , Hu Xuefei , Xie Dong , Zhao Deping , Li Qiuyuan , Guo Jianbo , Chen Chang ,   Surgical Thoracic Alliance of Rising Star Group
Published: September 2023

Background:

The eighth edition of nodal classification is defined only by anatomical location of metastatic lymph nodes and has limited prognostic discrimination power. We aimed to evaluate the prognostic significance and discriminatory capability of the number of metastatic lymph nodes (nN) in resected non-small cell lung cancer.

Materials and Methods:

Patients with stage IA to IIIB resected non-small cell lung cancer between January 1, 2009 to December 31, 2013 were analyzed as Chinese cohort. Optimal thresholds for the nN classification were determined by X-tile. The receiver operating characteristic curve, net reclassification improvement and standardized net benefit calculated by decision curve analysis was estimated to quantify the nN classification’s performance in prognostic stratification. External validation in the Surveillance, Epidemiology, and End Results database was performed to test the robustness of nN classification.

Results:

Both cohorts showed a stepwise prognosis deterioration with increasing nN. One to three, four to six, and more than six were selected as optimal thresholds of nN classification in the Chinese cohort which included 4,432 patients, then validated in the SEER cohort (n=28,022 patients). Multivariate Cox analysis showed the nN classification was an independent predictive factor for overall survival in both cohorts (Chinese cohort and SEER cohort: N0 vs. N1-3, P<0.001; N0 vs. N3-6, P<0.001; N0 vs. N>6, P<0.001). And prognostic discriminatory capability was improved in the nN classification compared with location-based N classification [5-year NRI score, 0.106 (95% CI, 0.049-0.132) and 5-year time-independent AUC, 0.593(95% CI, 0.560-0.625) vs. 0.554(95%CI, 0.520-0.588), P<0.001].

Conclusions:

The nN classification tended to be a superior prognostic indicator than location-based N classification. The number of metastatic lymph nodes should be considered in the future revision of TNM system.
Impact of lymphadenectomy extent on immunotherapy efficacy in post-resectional recurred non-small cell lung cancer: a multi-institutional retrospective cohort study
Authors: Deng Hongsheng , Zhou Juan , Chen Hualin , Cai Xiuyu , Zhong Ran , Li Feng , Cheng Bo , Li Caichen , Jia Qingzhu , Zhou Caicun , Petersen René Horsleben , Rocco Gaetano , Brunelli Alex , Ng Calvin S.H. , D’Amico Thomas A. , Su Chunxia , He Jianxing , Liang Wenhua , Zhu Bo ,   on behalf of the AME Thoracic Surgery Collaborative Group
Published: September 2023

Background:

Lymph node (LN) dissection is a common procedure for non-small cell lung cancer (NSCLC) to ascertain disease severity and treatment options. However, murine studies have indicated that excising tumor-draining LNs diminished immunotherapy effectiveness, though its applicability to clinical patients remains uncertain. Hence, we aim to illustrate the immunological implications of LN dissection by analyzing the impact of dissected LN (DLN) count on immunotherapy efficacy, and to propose a novel “immunotherapy-driven” LN dissection strategy.

Materials and Methods:

We conducted a retrospective analysis of NSCLC patients underwent anti-PD-1 immunotherapy for recurrence between 2018 and 2020, assessing outcomes based on DLN count stratification.

Results:

A total of 144 patients were included, of whom 59 had DLN count≤16 [median, IQR: 11, 7-13]; 66 had DLN count>16 [median, IQR: 23, 19-29]. With a median follow-up time of 14.3 months (95%CI: 11.0-17.6), the overall median PFS was 7.9 (95%CI: 4.1-11.7) months, 11.7 (95%CI: 7.9-15.6) months in the combination-therapy subgroup, and 4.8 (95%CI: 3.1-6.4) months in the immunotherapy alone subgroup, respectively. In multivariable Cox analysis, DLN count≤16 is associated with an improved PFS in all cohorts [Primary cohort: HR=0.26 (95%CI: 0.07-0.89), P=0.03; Validation cohort: HR=0.46 (95%CI: 0.22-0.96, P=0.04); Entire cohort: HR=0.53 (95%CI: 0.32-0.89), P=0.02]. The prognostic benefit of DLN count≤16 was more significant in immunotherapy alone, no adjuvant treatment, pN1, female, and squamous carcinoma subgroups. A higher level of CD8+ central memory T cell (Tcm) within LNs was associated with improved PFS (HR: 0.235, 95% CI: 0.065-0.845, P=0.027).

Conclusions:

An elevated DLN count (cutoff: 16) was associated with poorer immunotherapy efficacy in recurrent NSCLC, especially pronounced in immunotherapy alone subgroup. CD8+Tcm proportions in LNs may also impact immunotherapy efficacy. Therefore, for patients planned for adjuvant immunotherapy, a precise rather than expanded lymphadenectomy strategy to preserve immune-depending LNs is recommended.
Risk assessment of pneumothorax in colorectal lung metastases treated by percutaneous thermal ablation: A multicenter retrospective cohort study
Authors: Fan Hongjie , Xie Xuancheng , Pang Zhenzhu , Zhang Licai , Ding Rong , Wan Cheng , Li Xinghai , Yang Zebin , Sun Jihong , Kan Xuefeng , Tang Bufu , Zheng Chuansheng
Published: September 2023

Purpose:

To evaluate the risk of pneumothorax in the percutaneous image-guided thermal ablation (IGTA) treatment of colorectal lung metastases (CRLM).

Methods:

Data regarding patients with CRLM treated with IGTA from five medical institutions in China from 2016 to 2023 were reviewed retrospectively. Pneumothorax and non-pneumothorax were compared using the Student’s t test、Chi-square test and Fisher’s exact test. Univariate logistic regression analysis was conducted to identify potential risk factors, followed by multivariate logistic regression (MLR) analysis to evaluate the predictors of pneumothorax. Interactions between variables were examined and used for model construction. Receiver operating characteristic (ROC) curves and nomograms were generated to assess the performance of the model.

Results:

A total of 254 patients with 376 CRLM underwent 299 ablation sessions. The incidence of pneumothorax was 45.5%. The adjusted MLR model, incorporating interaction terms, revealed that tumor number (odds ratio [OR]=8.34 [95% confidence interval [CI]: 1.37-50.64]), puncture depth (OR=0.53 [95%CI: 0.31-0.91]), pre-procedure radiotherapy (OR=3.66 [95%CI: 1.17-11.40]), peri-bronchial tumor (OR=2.32 [95%CI: 1.04-5.15]), and emphysema (OR=56.83 [95%CI: 8.42-383.57]) were significant predictive factors of pneumothorax (all P<0.05). The generated nomogram model demonstrated a significant prediction performance, with an area under the ROC curve of 0.800 (95%CI: 0.751-0.850).

Conclusions:

Pre-procedure radiotherapy, tumor number, peri-bronchial tumor, and emphysema were identified as risk factors for pneumothorax in the treatment of CRLM using percutaneous IGTA. Puncture depth was found to be a protective factor against pneumothorax.
Early oral feeding versus nasojejunal early enteral nutrition in patients following pancreaticoduodenectomy: a propensity score-weighted analysis of 428 consecutive patients
Authors: Jing Wei , Wu Shengyong , Gao Suizhi , Shi Xiaohan , Liu Wuchao , Ren Yiwei , Ouyang Liu , Zheng Kailian , Guo Shiwei , Wu Cheng , Jin Gang
Published: September 2023

Background:

Notwithstanding that significant medical progress has been achieved in recent years, the optimal nutritional support method following pancreaticoduodenectomy (PD) remains uncertain. This study compared the safety and feasibility of early oral feeding (EOF) with nasojejunal early enteral nutrition (NJEEN) after PD.

Methods:

A retrospective cohort study was conducted on 428 consecutive patients who underwent PD between August 2018 and December 2020. During the first study phase, the routine postoperative feeding strategy was NJEEN, later replaced by EOF during the second study phase. The primary outcome was the incidence of delayed gastric emptying (DGE) following PD. Propensity score weighting (PSW) was used to control for confounding factors.

Results:

440 patients underwent PD during the overall study period, with 438 patients aged 18 years and older. Ten patients experienced accidental tube dislodgement or migration and were excluded from the study based on the exclusion criteria. Finally, 211 patients and 217 patients underwent EOF and NJEEN, respectively. After PSW, it was observed that patients who underwent postoperative EOF experienced a significantly lower DGE (B/C) rate compared to those who underwent postoperative NJEEN (7.38% (31/424) vs. 14.97% (62/413), P=0.0005). Subgroup analyses according to the presence of soft pancreatic texture yielded consistent results. The EOF group exhibited lower DGE grade, DGE (B/C) rate (5.90% (11/194) vs. 22.07% (43/193), P<0.0001), postoperative gastrointestinal endoscopic intervention rate, and Clavien-Dindo Grade III or higher rate.

Conclusions:

EOF is superior to NJEEN in reducing the incidence of grade B/C DGE after PD. The EOF procedure is safe and feasible and should be recommended as the optimal postoperative feeding method following PD.
Reappraisal of optimal reconstruction after distal gastrectomy – a study based on KLASS-07 database
Authors: Park Shin-Hoo , Hur Hoon , Park Jong-Hyun , Lee Chang-Min , Son Young-Gil , Jung Mi Ran , Lee Han Hong , Hwang Sun-Hwi , Lee Moon-Soo , Seo Sang Hyuk , Jeong In Ho , Son Myoung Won , Kim Chang Hyun , Yoo Moon-Won , Oh Sung Jin , Hwang Seong Ho , Il Choi Sung , Choi Hyuk Soon , Keum Bo-Ra , Yang Kyung Sook , Park Sungsoo
Published: September 2023

Backgrounds:

This study aimed to compare the incidence of bile reflux, quality of life (QoL), and nutritional status among Billroth II (BII), Billroth II with Braun anastomosis (BII-B), and Roux-en-Y (RY) reconstruction after laparoscopic distal gastrectomy (LDG).

Material and methods:

We reviewed the prospective data of 397 patients from a multicentre database who underwent LDG for gastric cancer between 2018 and 2020 at 20 tertiary teaching hospitals in Korea. Postoperative endoscopic findings, QoL surveys using European Organization for Research and Treatment of Cancer questionnaire (C30 and STO22), and nutritional and surgical outcomes were compared among groups.

Results:

In endoscopic findings, bile reflux was the lowest in the RY group (n=67), followed by the BII-B (n=183) and BII groups (n=147) at 1 year (3.0% vs. 67.8% vs. 84.4%, all P<0.05). The anti-reflux capability of BII-B was statistically better than that of BII, but not as perfect as that of RY. From the perspective of QoL, BII-B was not inferior to RY, but better than BII reconstruction in causing fewer STO22 reflux symptoms at 6 and 12 months. However, only RY caused fewer C30 nausea symptoms than BII at 6 and 12 months, but not BII-B. Nutritional status and morbidities were similar among the three groups, and the operative time did not differ between the BII-B and RY groups.

Conclusions:

BII-B cannot substitute for RY in preventing bile reflux, shortening the operative time, or reducing morbidities. Regarding short-term QoL, BII-B was sufficient to reduce STO22 reflux symptoms, but failed to reduce C30 nausea symptoms, postoperatively.
Change in Health-Related Quality of Life in Youth with Chronic Hepatitis B Living in North America: A 5-Year Cohort Study
Authors: Schwarzenberg Sarah Jane , King Wendy C. , Ling Simon C. , Murray Karen F. , Mogul Douglas , Rosenthal Philip , Rodriguez-Baez Norberto , Teckman Jeffrey , Schwarz Kathleen B. ,   for the Hepatitis B Research Network (HBRN)
Published: September 2023

Background:

Greater hepatitis-related symptomology is associated with lower health-related quality-of-life (HRQoL) among untreated youth with chronic hepatitis B (CHB). How HRQoL changes over time in this population is unknown.

Methods:

Children from 7 hepatology centers in North America positive for hepatitis B surface antigen, not taking anti-viral therapy, were enrolled in the Hepatitis B Research Network. A validated self-report HRQoL measure, the Child Health Questionnaire Child Report (CHQ-CF87), was completed annually by participants 10–17 years, with demographic variables, liver disease symptoms, and laboratory tests. Linear mixed-effects models were used to evaluate the 10 CHQ-CF87 subscale scores over 5 years among participants who completed the CHQ-CF87 at least twice.

Results:

Participants (N = 174) completed the CHQ-CF87 a median of 4 times. Median age was 12 years (interquartile range: 10–14) at baseline; 60% were female, 79% Asian, and 47% adopted. The CHQ-CF87 subscale scores were high at baseline (median range: 75.4–100) and did not differ by time point, except for the Family Activities subscale (mean [95% CI]: 82.3 [79.8–84.8] at baseline; 90.8 [86.1–94.6] week 240). Most subscale scores lacked sufficient individual-level variability in change over time to evaluate predictors. Being White versus Asian predicted a more favorable change in Behavior (6.5 [95% CI: 2.0–11.0]). Older age predicted less favorable change in Mental Health (−0.8 [95% CI: −1.36 to −0.23] per year). Changes in liver enzymes and hepatitis B antigens, DNA, or symptom count were not related to changes in these subscale scores.

Conclusion:

HRQoL was generally good and consistent across 5 years in youth with CHB.
Effects of ankle-foot orthosis on gait pattern and spatiotemporal indices during treadmill walking in hemiparetic stroke
Authors: Ohtsuka Kei , Mukaino Masahiko , Yamada Junya , Fumihiro Matsuda , Tanikawa Hiroki , Tsuchiyama Kazuhiro , Teranishi Toshio , Saitoh Eiichi , Otaka Yohei
Published: September 2023

Ankle-foot orthosis (AFO) is known to correct abnormal gait patterns and improve walking stability and speed in patients with hemiparesis. To quantify these benefits in post-stroke gait, a three-dimensional motion analysis of gait pattern was conducted. Forty patients with hemiparesis were enrolled. A three-dimensional motion analysis system was used to analyze patients’ treadmill walking with/without an AFO. Outcome measures were 12 abnormal gait indices (forefoot contact, knee extensor thrust, retropulsion of the hip, flexed-knee gait, medial whip in the stance phase, circumduction gait, hip hiking, insufficient knee flexion during the swing phase, excessive lateral shifting of the trunk, contralateral vaulting, excessive hip external rotation, and posterior pelvic tilt), calculated using kinematic data and spatiotemporal indices, and the symmetry index of double-stance and single-stance time and step length. Forefoot contact (without AFO vs. with AFO: 71.0 vs. 65.8, P < 0.001), circumduction gait (65.0 vs. 57.9, P < 0.001), and contralateral vaulting (78.2 vs. 72.2, P = 0.003) were significantly reduced, whereas excessive hip external rotation (53.7 vs. 62.8, P = 0.003) significantly increased during walking with an AFO. Hip hiking (77.1 vs. 71.7) showed marginal reduction with the use of AFO (P = 0.096). The absolute symmetry index of double-stance time (21.9 vs. 16.1, P = 0.014) significantly decreased during walking with an AFO. AFO effectively mitigates abnormal gait patterns typical of hemiparetic gait. A 3D motion analysis system with clinically oriented indices can help assess intervention efficacy for gait abnormalities.
Success rates of endotracheal intubation using the standard method versus the modified-ramped position
Authors: Lotfi Sarah , Mohamadi Mohamad sepehr , Ahmadi Abbas , Rezvani Sourena , Sehat Malihe , Tabaraii Reihane
Published: September 2023

Background:

The sniffing position used in intubation has disadvantages, including suboptimal glottic view, respiratory problems, increased risk of aspiration, and pain. In this regard, we have proposed new conditions to facilitate intubation and tube placement in patients with a Mallampati score higher than 2, by introducing a new position called the modified rapid airway management positioner (RAMP) position. The authors compared various parameters to improve intubation conditions between these two positions.

Methods:

This intervention is a randomized clinical trial study, with a random sampling method that divides the patients into two groups: a control group placed in the standard position (S) and an intervention group placed in the modified (M) RAMP position. An anesthesiologist performed intubation. In group (S), patients were placed in the supine position as usual, and a pillow with a height of 10 cm was placed under their heads. In group (M), the patients were placed in the supine position on a modified RAMP with a triangular shape, 15 cm in height, and 80 cm in length, at a 30° angle. The pillow had lengths of 20 and 80 cm.

Results:

In the present study, 112 patients were investigated, consisting of 58 women (51.8%) and 54 men (48.2%). The intubation time in the intervention group using the modified RAMP roll technique was significantly shorter (51.25 s) compared to the control group using the standard method (88.39 s) (P=0.019).

Conclusion:

The results of the study showed that the modified RAMP roll improved the general conditions of intubation and led to a better view of the glottis in direct laryngoscopy. This is a very important aspect of intubation, and with a better view of the pharynx and glottis, the intubation procedure can be performed with higher quality, reducing the number of intubation attempts and the duration of the procedure.
Recent advances in three-dimensional ultrasound virtual cystoscopy in modeling and local staging for urothelial carcinoma with histopathological correlation: a cohort prospective study
Authors: Mohamed Hassan Ismail , Aly Mahmoud , Badran Yasser , Fawzy Mohamed , El-damanhory Hany , Gomma Aly , Ghoneimy Osama M. , Abdelaleem Mohamed F. , Elsharkawy Moataz , Fayad Sherif , Zidan Ahmed M. , Soltan Hassan A. , Samih Tamer A.A. , Aboelsaad Ahmed Y. , Abdel Gawad Ahmed M. , Moustafa Bahaa-Eldin Ahmed , Abbas Hesham , Aly Noha M. , Elhawary Reda , Hasan Abdulkarim
Published: September 2023

Background:

Bladder urothelial carcinoma is an alarming urologic malignancy. Complex factors like modelling and local staging can affect treatment strategy. However, local staging, particularly the muscle invasion status, significantly influences decisions regarding treatment strategies. Therefore, this study aims to evaluate the novel advances of three-dimensional (3D) ultrasound (US) imaging to assess local staging in comparison with conventional cystoscopy.

Methods:

Forty-three patients with painless haematuria and conventional cystoscopy findings of bladder mass underwent 3D US virtual cystoscopy. All specimens from conventional cystoscopy were processed histologically.

Results:

Out of 43 participants, 18 (41.9%) patients proved to have invasive urothelial carcinoma by histopathology. The 3D US had a sensitivity of 97.5% and a specificity of 100%; however conventional cystoscopy was accurate in only 53.5% of the studied cases. Furthermore, in the case of malignant ulcers, mural extension into both the submucosal and the muscle layers was more readily appreciated in multiplanar images.

Conclusion:

3D US updates are promising for use in bladder tumour modelling and local staging; however, they can be of value in evaluating mural and extramural tumour extent and have proven accuracy.
The Research Accelerator Program: A strategic initiative to facilitate interdisciplinary collaboration that advances translational research
Authors: Briody Melissa A. , Rafferty Miriam R. , Fahey Meghan , Sliwa James A. , Lieber Richard L.
Published: September 2023

Developing a culture of innovative thinking and one that emphasizes clinician-researcher interaction is critical for the future of rehabilitation. We designed and implemented a strategy to build a culture of interdisciplinary communication and collaboration that facilitates translational research across several disciplines in our inpatient rehabilitation hospital. We co-located clinicians and researchers in workspaces within a new hospital and created the Research Accelerator Program— a collection of team-focused initiatives that promote communication and collaboration among researchers, clinicians, and other staff. The purpose of this article is to disseminate this strategy, which has increased staff participation in research activities and increased scientific productivity of interdisciplinary research teams over the past eight years.
Examining diversity recruitment efforts in US-Based Physical Medicine and Rehabilitation residencies: A survey of program directors on gender, ethnic and racial diversity and Implications for Recruitment efforts
Authors: Barylski Nicole , Henson Philip , Verduzco-Gutierrez Monica , Escalon Miguel X.
Published: September 2023

As the population of the United States (US) continues to grow and diversify, it is critical that the medical profession follows. This study aimed to evaluate aspects of the current landscape of diversity within physical medicine and rehabilitation (PM&R) by surveying program directors (PDs) of US-based PM&R residencies. The secondary aim was to identify program characteristics that correlate with more diverse residency classes. An online, cross-sectional 17-question survey was distributed to PDs of all US-based PM&R residencies with known contact information (95/100), with a completed survey response rate of 53% (50/95). Race and ethnicity categories of the survey were based on those used by the US Census. The percentages of individuals identifying as women or those underrepresented in medicine (URiM) in this survey were below those of the general US population, a trend also seen within the field of PM&R overall. Linear regression revealed no statistically significant association between the percentage of URiM residents and commonly used diversity recruitment initiatives. There was a significant association between the presence of a departmental role for DEI and the percentage of women residents (OR 1.13; p = 0.017). Continued research is required to identify additional strategies with demonstrated efficacy in recruiting diverse residency applicants.
Doravirine Plus Integrase Strand Transfer Inhibitors as a 2-Drug Treatment–Switch Strategy in People Living with HIV: The Real-Life DORINI Multicentric Cohort Study
Authors: Poliseno Mariacristina , Mazzitelli Maria , Narducci Arianna , Ferrara Sergio Maria , Resnati Chiara , Gervasoni Cristina , Cattelan Anna Maria , Lo Caputo Sergio
Published: September 2023

Background:

Few data are available about the efficacy, durability, and tolerability of doravirine (DOR) + integrase strand inhibitors (INI) as a switching strategy among antiretroviral therapy (ART)–experienced people living with HIV (PLWH).

Setting:

Retrospective, multicenter cohort study investigating the durability, efficacy, and tolerability of 2 off-label drug associations of DOR + INI among ART-experienced PLWH.

Methods:

The study included PLWH who switched to DOR combined with either raltegravir (RAL) or dolutegravir (DTG) between June 1, 2020, and December 31, 2021, with at least 1 follow-up (FU) visit. Virologic, biometric, and metabolic parameters were evaluated at baseline (T0) and at 1–3 (T1), 6 (T2), and 12 (T3) months. Univariate and multivariate survival analyses assessed the 28-week probability of persistence on the regimens. Patient satisfaction was measured using the HIV Treatment Satisfaction Questionnaire.

Results:

Ninety-five PLWH were included, 52 in DOR + RAL and 43 in DOR + DTG. Six treatment discontinuations were reported during a mean of 37 (±17) weeks of FU (incidence of 2.7 × 1000 person-weeks FU). Only 2 were the result of virological failure without resistance mutations. DOR + DTG demonstrated significantly higher 28-week persistence than DOR + RAL (HR 1.90, 95% CI: 1.24–2.90, log-rank: P = 0.003). Weight, waist circumference, and fasting lipids reduced considerably at T3 vs T0. Overall, high satisfaction with the new treatment was reported, particularly in the DOR + RAL (68 (64–72)/72), compared with the DOR + DTG group (58 (50–65)/72, P< 0.001).

Conclusions:

Our experience revealed few treatment discontinuations, improved metabolic parameters, and high patient satisfaction among ART-experienced PLWH switching to DOR combined with INI, irrespective of the specific INI used.
Effectiveness of an Integrated Ambulatory Care Program in Health Care and Medication Use in Patients With Multimorbidity and Polypharmacy
Authors: Lo Yu-Tai , Chen Mei-Hua , Chen Pin-Hao , Lu Feng-Hwa , Chang Chia-Ming , Yang Yi-Ching
Published: September 2023

Background and Objectives:

Multimorbidity increases risks, such as polypharmacy, inappropriate prescription, and functional decline. It also increases medical care utilization by older adults, placing a burden on health care systems. This study evaluated the effectiveness of an integrated ambulatory care program for health care and medication use in patients with multimorbidity and polypharmacy.

Methods:

We conducted a retrospective clinical review of adults with multimorbidity and polypharmacy who attended an integrated ambulatory care program at a 1193-bed university hospital between July 1 and September 30, 2019. This program involves multidisciplinary teamwork, comprehensive assessments, medication reviews, and case management. Outcomes, including the frequency of outpatient visits, emergency department visits, hospitalizations, chronic prescription medications, potentially inappropriate medications (PIMs), health care costs, and total medical expenditure, were compared before and after the program.

Results:

The mean age of participants (n = 134) at baseline was 74.22 ± 9.75 years. The mean number of chronic diagnoses was 9.45 ± 3.38. Participants included 72 (53.7%) women. At the 1-year follow-up, participants showed a significant decrease in the annual frequency of outpatient visits (19.78 ± 9.98 to 13.90 ± 10.22, P < .001), emergency department visits (1.04 ± 1.70 to 0.73 ± 1.40, P = .029), and chronic disease medications (10.71 ± 3.96 to 9.57 ± 3.67, P < .001) across all age groups. There was also a reduction in the annual number of PIMs (from 1.31 ± 1.01 to 1.12 ± 0.93, P = .002) among patients aged 65 years. However, no effects were observed on annual hospitalization, duration of hospital stay, or total health care expenditure, possibly due to the high disease-related treatment cost for certain participants.

Conclusions:

Expanding integrated ambulatory care programs in Taiwan may help patients with multimorbidity reduce their use of outpatient and emergency services, chronic prescriptions, and PIMs.
Potential Approach to Quantifying the Volume of the Ischemic Core in Truncated Computed Tomography Perfusion Scans: A Preliminary Study
Authors: Xu Xiao-Quan , Cao Lin-Li , Ma Gao , Shen Guang-Chen , Lu Shan-Shan , Zhang Ya-Xi , Zhang Yu , Shi Hai-Bin , Liu Sheng , Wu Fei-Yun
Published: September 2023

Objective

This study aimed to provide an alternative approach for quantifying the volume of the ischemic core (IC) if truncation of computed tomography perfusion (CTP) occurs in clinical practice.

Methods

Baseline CTP and follow-up diffusion-weighted imaging (DWI) data from 88 patients with stroke were retrospectively collected. CTP source images (CTPSI) from the unenhanced phase to the peak arterial phase (CTPSI-A) or the peak venous phase (CTPSI-V) were collected to simulate the truncation of CTP in the arterial or venous phases, respectively. The volume of IC on CTPSI-A (VCTPSI-A) or CTPSI-V (VCTPSI-V) was defined as the volume of the brain tissue with >65% reduction in attenuation compared with that of the normal tissue. The volume of IC on the baseline CTP (VCTP) was defined as a relative cerebral blood flow of <30% of that in the normal tissue. The volume of the posttreatment infarct on the follow-up DWI (VDWI) image was manually delineated and calculated. One-way analysis of variance, Bland-Altman plots, and Spearman correlation analyses were used for the statistical analysis.

Results

VCTPSI-A was significantly higher than VDWI (P < 0.001); however, no significant difference was observed between VCTP and VDWI (P = 0.073) or between VCTPSI-V and VDWI (P > 0.999). The mean differences between VDWI and VCTPSI-V, VDWI and VCTP, and VDWI and VCTPSI-A were 1.70 mL (limits of agreement [LoA], −56.40 to 59.70), 8.30 mL (LoA, −40.70 to 57.30), and −68.10 mL (LoA, −180.90 to 44.70), respectively. Significant correlations were observed between VDWI and VCTP (r = 0.68, P < 0.001) and between VDWI and VCTPSI-V (r = 0.39, P < 0.001); however, no significant correlation was observed between VDWI and VCTPSI-A (r = 0.20, P = 0.068).

Conclusions

VCTPSI-V may be a promising method for quantifying the volume of the IC if truncation of CTP occurs.
Partial Radiation Nephrectomy Using 90Y Resin Microspheres: A Treatment Option for Renal Tumors With Malignant Characteristics in Patients Not Candidates for Surgery
Authors: Sogbe Miguel , Rodríguez-Fraile Macarena , de la Cuesta Antonio Martínez , Rotellar Fernando , Iñarrairaegui Mercedes
Published: September 2023

Contrast-enhancing renal masses are likely to be malignant in over 90% of cases due to the high diagnostic accuracy of abdominal imaging. In this situation, tumor biopsy is unnecessary and should be managed as a renal cell carcinoma. Resection remains the only potentially curative treatment. However, as in the case herein presented, comorbidities can prevent surgical resection. Radioembolization with 90Y microspheres is an intra-arterial procedure capable of delivering high doses of radiation to tumors. The present case demonstrates the concept of partial radiation nephrectomy in treating renal tumors with malignant characteristics in patients not amenable to surgery.
Langerhans Cell Histiocytosis With Thyroid Involvement on 18F-FDG PET/MR
Authors: Lee Hwan , States Lisa J.
Published: September 2023

An 18-month-old otherwise healthy girl presented with 1 month of neck swelling. Based on ultrasonography that showed diffusely enlarged heterogeneous thyroid gland, a presumed diagnosis of thyroid cancer was made. Subsequent core needle biopsy revealed Langerhans cell histiocytosis extensively involving the thyroid. 18F-FDG PET/MR was performed for staging and to evaluate the local extent of the disease in the neck. PET/MR demonstrated a hypermetabolic neck mass inseparable from the thyroid gland. The mass encased the major vessels, trachea, and esophagus without compression or invasion. Osseous involvement was excluded by both skeletal survey and PET/MR.
Leptomeningeal Metastasis From Neuroblastoma Revealed by 123I-MIBG SPECT/CT
Authors: Feng Lijuan , Lu Xia , Wang Wei , Yang Jigang
Published: September 2023

A 2-year-old girl with history of high-risk neuroblastoma underwent 123I-MIBG, which showed increased 123I-MIBG in the left side of the head. Contrast-enhanced MRI and cerebral spine fluid cytology confirmed the diagnosis of leptomeningeal metastasis.
Evaluation of components of the extracellular purinergic signaling system in human sepsis
Authors: Lovászi Marianna , Németh Zoltán H , Kelestemur Taha , Sánchez Itzel V. , Antonioli Luca , Pacher Pál , Wagener Gebhard , Haskó György
Published: September 2023

Objective

Extracellular purines such as ATP, UTP and UDP and the ATP degradation product adenosine are biologically active signaling molecules, which accumulate at sites of metabolic stress in sepsis. They have potent immunomodulatory effects by binding to and activating P1 or adenosine and P2 receptors on the surface of leukocytes. Here we assessed the levels of extracellular purines, their receptors, metabolic enzymes and cellular transporters in leukocytes of septic patients.

Methods

Peripheral blood mononuclear cells (PBMCs), neutrophils and plasma were isolated from blood obtained from septic patients and healthy control subjects. RNA was isolated from cells and mRNA levels for purinergic receptors, enzymes, and transporters were measured. ATP, UTP, UDP and adenosine levels were evaluated in plasma.

Results

ATP levels were lower in septic patients than in healthy individuals and levels of the other purines were comparable between the two groups. Levels of P1 and P2 receptors did not differ between the two patient groups. mRNA levels of ectonucleoside triphosphate diphosphohydrolase (NTPDase)1 or CD39 increased while those of NTPDase2, -3 and -8 decreased in PBMCs of septic patients when compared to healthy controls. CD73 mRNA was lower in PBMCs of septic than healthy individuals. Equilibrative nucleoside transporter (ENT)1 mRNA concentrations were higher and ENT2, 3, and 4 mRNA concentrations were lower in PBMCs of septic subjects when compared to healthy subjects. Concentrative nucleoside transporter (CNT)1 mRNA levels were higher in PBMCs of septic vs. healthy subjects whereas the mRNA levels of CNT2, 3, and 4 did not differ. We failed to detect differences in mRNA levels of purinergic receptors, enzymes and transporters in neutrophils of septic vs. healthy subjects.

Conclusion

Since CD39 degrades ATP to AMP, the lower ATP levels in septic individuals may be the result of increased CD39 expression. This increased degradation of ATP did not lead to increased adenosine levels, which may be explained by the decreased expression of CD73, which converts AMP to adenosine. Altogether, our results demonstrate differential regulation of components of the purinergic system in PBMCs during human sepsis.
Prospective Examination of the K/iCa Ratio as a Predictor for Mortality in Severe Hemorrhage
Authors: Gagen Brennan , Duchesne Juan , Ghio Michael , Duplechain Abby , Krakosky Danielle , Simpson John T. , Tatum Danielle
Published: September 2023

BACKGROUND

Patients receiving massive transfusion protocol (MTP) are at risk for post-transfusion hypocalcemia and hyperkalemia. Previous retrospective analysis has suggested the potassium/ionized calcium (K/iCa) ratio as a prognostic indicator of mortality. This prospective study sought to validate the value of the K/iCa ratio as a predictor for mortality in patients receiving MTP.

METHODS

This was a prospective analysis of adult trauma patients who underwent MTP activation from May 2019 - March 2021 at an urban Level 1 trauma center. Serum potassium and ionized calcium levels within 0-1 hr of MTP initiation were used to obtain K/iCa. Receiver operator characteristic (ROC) curve analysis assessed predictive capacity of K/iCa on mortality. Kaplan-Meier survival analysis and Cox regression examined the effect of K/iCa ratio on survival.

RESULTS

A total of 110 of 300 MTP activation patients met inclusion criteria. Overall mortality rate was 31.8%. No significant differences between the elevated K/iCa and lower K/iCa groups were found for prehospital or Emergency Department initial vitals, shock index, or injury severity. However, non-survivors had a significantly higher median K/iCa ratio compared to those who survived (p < 0.01). Multivariable logistic regression revealed total number of blood products to be significantly associated with elevated K/iCa (odds ratio 1.02; 95%CI 1.01-1.04; p = 0.01). The KM survival curve demonstrated a significantly increased rate of survival for those with an elevated K/iCa ratio (p < 0.01). Multivariable Cox regression adjusted for confounders showed a significant association between K/iCa and mortality (HR 4.12, 95% CI 1.89 – 8.96, p < 0.001).

CONCLUSION

This evidence further highlights the importance of the K/iCa ratio in predicting mortality among trauma patients receiving MTP. Furthermore, it demonstrates that post-transfusion K levels along with iCa levels should be carefully monitored in the MTP setting.

LEVEL OF EVIDENCE

Level II

STUDY TYPE

Prognostic/Epidemiological
Outcomes and Risk Factors for Liver Transplantation Using graft-to-Recipient Weight Ratio Less than 0.8 Graft from Living Donors: Multicentric Cohort Study
Authors: Kim Deok-Gie , Hwang Shin , Kim Jong Man , Choi YoungRok , You Young Kyoung , Choi Donglak , Ryu Je Ho , Kim Bong-Wan , Kim Dong-Sik , Cho Jai Young , Ju Man ki , Kim Tae-Seok , Nah Yang Won , Lee Jae Geun , Kim Myoung Soo , Joo Dong Jin ,   the Korean Organ Transplantation Registry Study Group
Published: September 2023

Objective:

To compare graft survival after LDLT in patients receiving GRWR<0.8 versus GRWR≥0.8 grafts and identify risk factors for graft loss using GRWR<0.8 grafts.

Summary Background Data:

Favorable outcomes after living donor liver transplantation (LDLT) using graft-to-recipient weight ratio (GRWR)<0.8 grafts were recently reported; however, these results have not been validated using multicenter data.

Methods:

This multicentric cohort study included 3450 LDLT patients. Graft survival was compared between 1:3 propensity score–matched groups and evaluated using various Cox models in the entire population. Risk factors for graft loss with GRWR<0.8 versus GRWR≥0.8 grafts were explored within various subgroups using interaction analyses, and outcomes were stratified according to the number of risk factors.

Results:

In total, 368 patients (10.7%) received GRWR<0.8 grafts (GRWR<0.8 group), whereas 3082 (89.3%) received GRWR≥0.8 grafts (GRWR≥0.8 group). The 5-y graft survival rate was significantly lower with GRWR<0.8 grafts than with GRWR≥0.8 grafts (85.2% vs. 90.1%, P=0.013). Adjusted hazard ratio (HR) for graft loss using GRWR<0.8 grafts in the entire population was 1.66 (95% confidence interval [CI] 1.17–2.35, P=0.004). Risk factors exhibiting significant interactions with GRWR<0.8 for graft survival were age ≥60 y, MELD score ≥15, and male donor. When ≥2 risk factors were present, GRWR<0.8 grafts showed higher risk of graft loss compared to GRWR≥0.8 graft in LDLT (HR 2.98, 95% CI 1.79–4.88, P<0.001).

Conclusions:

GRWR<0.8 graft showed inferior graft survival than controls (85.2% vs. 90.1%), especially when ≥2 risk factors for graft loss (among age ≥60 y, MELD score ≥15, or male donor) were present.
2022 Wilkins–Bernal–Medawar Lecture Remaking Ourselves: Technologies of Flesh and the Futures of Selfhood
Authors: Ball Philip
Published: September 2023

Our biotechnologies have entered uncharted territory. The facility for precision editing of the human genome raises the prospect of systematic, ‘post-Darwinian’ control of inheritance. Stem cells can be used to make embryo-like structures that were never fertilized eggs and which might or might not recapitulate normal embryonic development. Neural ‘organoids’ grown in a dish force us to ask what are the minimal substrates of consciousness. It is easy to spin dystopian tales out of such developments, but those offer little guidance for the more urgent issue of how to regulate these technologies or how to discuss their ethical and societal implications. Here I argue for the importance, in those debates, of keeping historical and cultural perspectives visible and explicit: on the one hand to recognize the deep roots of the more lurid fantasies that these developments evoke, and on the other hand to consider how the latest advances challenge the narratives that scientists themselves have employed to frame their research. We should be prepared to be unsettled by what in 1890 zoologist Jacques Loeb called ‘a technology of living substance’—but perhaps not necessarily in ways we can anticipate.
Non-invasive investigation of the morphology and optical properties of the upside-down jellyfish
Cassiopea
with optical coherence tomography
Authors: Lyndby Niclas Heidelberg , Murthy Swathi , Bessette Sandrine , Jakobsen Sofie Lindegaard , Meibom Anders , Kühl Michael
Published: September 2023

The jellyfish
Cassiopea
largely cover their carbon demand via photosynthates produced by microalgal endosymbionts, but how holobiont morphology and tissue optical properties affect the light microclimate and symbiont photosynthesis in
Cassiopea
remain unexplored. Here, we use optical coherence tomography (OCT) to study the morphology of
Cassiopea
medusae at high spatial resolution. We include detailed 3D reconstructions of external micromorphology, and show the spatial distribution of endosymbionts and white granules in the bell tissue. Furthermore, we use OCT data to extract inherent optical properties from light-scattering white granules in
Cassiopea,
and show that granules enhance local light-availability for symbionts in close proximity. Individual granules had a scattering coefficient of
µ
s
= 200–300 cm
−1
, and scattering anisotropy factor of
g
= 0.7, while large tissue-regions filled with white granules had a lower
µ
s
= 40–100 cm
−1
, and
g
= 0.8–0.9. We combined OCT information with isotopic labelling experiments to investigate the effect of enhanced light-availability in whitish tissue regions. Endosymbionts located in whitish tissue exhibited significantly higher carbon fixation compared to symbionts in anastomosing tissue (i.e. tissue without light-scattering white granules). Our findings support previous suggestions that white granules in
Cassiopea
play an important role in the host modulation of the light-microenvironment.