bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program
Authors: Frost Nikolaj , Christopoulos Petros , Kauffmann-Guerrero Diego , Stratmann Jan , Riedel Richard , Schaefer Monica , Alt Jürgen , Gütz Sylvia , Christoph Daniel C. , Laack Eckart , Faehling Martin , Fischer Richard , Fenchel Klaus , Haen Sebastian , Heukamp Lukas , Schulz Christian , Griesinger Frank 
Published: February 2021

Introduction: We report on the results of the German early access program (EAP) with the third-generation ALK- and ROS1-inhibitor lorlatinib. Patients and Methods: Patients with documented treatment failure of all approved ALK/ROS1-specific therapies or with resistance mutations not covered by approved inhibitors or leptomeningeal carcinomatosis were enrolled and analyzed. Results: In total, 52 patients were included [median age 57 years (range 32–81), 54% female, 62% never smokers, 98% adenocarcinoma]; 71% and 29% were ALK- and ROS1-positive, respectively. G1202R and G2032R resistance mutations prior to treatment with lorlatinib were observed in 10 of 26 evaluable patients (39%), 11 of 39 patients showed TP53 mutations (28%). Thirty-six patients (69%) had active brain metastases (BM) and nine (17%) leptomeningeal carcinomatosis when entering the EAP. Median number of prior specific TKIs was 3 (range 1–4). Median duration of treatment, progression-free survival (PFS), response rate and time to treatment failure were 10.4 months, 8.0 months, 54% and 13.0 months. Calculated 12-, 18- and 24-months survival rates were 65, 54 and 47%, overall survival since primary diagnosis (OS2) reached 79.6 months. TP53 mutations were associated with a substantially reduced PFS (3.7 versus 10.8 month, HR 3.3, p = 0.003) and were also identified as a strong prognostic biomarker (HR for OS2 3.0 p = 0.02). Neither prior treatments with second-generation TKIs nor BM had a significant influence on PFS and OS. Conclusions: Our data from real-life practice demonstrate the efficacy of lorlatinib in mostly heavily pretreated patients, providing a clinically meaningful option for patients with resistance mutations not covered by other targeted therapies and those with BM or leptomeningeal carcinomatosis.
Phase II study of liposomal doxorubicin, docetaxel and trastuzumab in combination with metformin as neoadjuvant therapy for HER2-positive breast cancer
Authors: Rocca Andrea , Cortesi Pietro , Cortesi Laura , Gianni Lorenzo , Matteucci Federica , Fantini Lorenzo , Maestri Antonio , Giunchi Donata Casadei , Cavanna Luigi , Ciani Rosa , Falcini Fabio , Bagni Antonella , Meldoli Elena , Dall’Agata Monia , Volpi Roberta , Andreis Daniele , Nanni Oriana , Curcio Annalisa , Lucchi Leonardo , Amadori Dino , Fedeli Anna 
Published: February 2021

Background: The aim of this study was to improve activity over single human epidermal growth factor receptor 2 (HER2)-blockade sequential neaodjuvant regimens for HER2-positive breast cancer, by exploiting the concomitant administration of trastuzumab, taxane and anthracycline, while restraining cardiac toxicity with use of liposomal doxorubicin, and by adding metformin, based on preliminary evidence of antitumor activity. Patients and methods: This multi-center, single-arm, two-stage phase II trial, assessed the safety and the activity of a new treatment regimen for HER2-positive, early or locally advanced breast cancer. Patients received six 21-day cycles of non-pegylated liposomal doxorubicin, 50 mg/m2 intravenously (i.v.) on day 1, docetaxel, 30 mg/m2 i.v. on days 2 and 9, trastuzumab, 2 mg/kg/week i.v. on days 2, 9, and 16 (with 4 mg/kg loading dose), in association with metformin 1000 mg orally twice daily. The primary endpoint was the rate of pathological complete response (pCR) in the breast and axilla (ypT0/is ypN0). A subgroup of patients performed a 3-deoxy-3-18F-fluorothymidine positron emission tomography (FLT-PET) at baseline and after one cycle. Results: Among 47 evaluable patients, there were 18 pCR [38.3%, 95% confidence interval (CI) 24.5–53.6%]. A negative estrogen-receptor status, high Ki67, and histological grade 3 were related with pCR, although only grade reached statistical significance. FLT-PET maximum standardized uptake value after one cycle was inversely related to pCR in the breast (odds ratio 0.29, 95% CI 0.06–1.30, p = 0.11). Toxicity included grade 3–4 neutropenia in 70% and febrile neutropenia in 4% of patients, grade 1–2 nausea/vomiting in 60%/38%, and grade 3 in 4%/2%, respectively, grade 1–2 diarrhea in 72%, and grade 3 in 6%. There were two cases of reversible grade 2 left-ventricular ejection-fraction decrease, and one case of sharp troponin-T increase. Conclusions: The concomitant administration of trastuzumab, liposomal doxorubicin, docetaxel, and metformin is safe and shows good activity, but does not appear to improve activity over conventional sequential regimens.
Effect of cannabis on oxaliplatin-induced peripheral neuropathy among oncology patients: a retrospective analysis
Authors: Waissengrin Barliz , Mirelman Dan , Pelles Sharon , Bukstein Felix , Blumenthal Deborah T. , Wolf Ido , Geva Ravit 
Published: February 2021

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dosage-limited oxaliplatin-related toxicity. To date, there are no successful interventions for CIPN prevention or treatment. A therapeutic role for cannabis in diabetic and HIV-related peripheral neuropathy and a protective role in CIPN have been suggested. We examined the effect of cannabis on oncologic patients with CIPN. Methods: Medical records of 768 consecutive patients treated with oxaliplatin and 5-fluorouracil-based combinations at a tertiary medical center from October 2015 to January 2018 were reviewed. Excluded patients were those with pre-existing neuropathy or patients who received fewer than two cycles of oxaliplatin treatment. CIPN grade, oxaliplatin cumulative dose, and neuropathy-free survival were evaluated. The patients were divided based upon the exposure to cannabis: prior to oxaliplatin (cannabis-first), cannabis following the initiation of oxaliplatin treatment (oxaliplatin-first), and no exposure (control). Results: In total, 513 patients met the inclusion criteria, of whom 248 were treated with cannabis and 265 served as controls. The cannabis-first group included 116 (46.7%) patients and the oxaliplatin-first group included 132 (53.3%) patients. Demographic parameters were comparable between groups. There was a significant difference in CIPN grade 2–3 between cannabis-exposed patients and controls (15.3% and 27.9%, respectively, p < 0.001). The protective effect of cannabis was more pronounced among cannabis-first patients compared to oxaliplatin-first patients (75% and 46.2%, respectively, p < 0.001). The median oxaliplatin cumulative doses were higher in the cannabis-first versus the oxaliplatin-first versus the control groups (545 mg/m2, 340 mg/m2, and 425 mg/m2 respectively, p < 0.001). Conclusion: The rate of neuropathy was reduced among patients treated with cannabis and oxaliplatin. This reduction was more significant in patients who received cannabis prior to treatment with oxaliplatin, suggesting a protective effect. A large prospective trial is planned.
Predictors of Improvement After Fasciotomy for Treatment of Chronic Exertional Compartment Syndrome of the Lower Extremity
Authors: Mangan John J. , Rogero Ryan G. , Fuchs Daniel J. , Raikin Steven M. 
Published: February 2021

Background: Previous studies have demonstrated the effectiveness of lower extremity fasciotomies in treating chronic exertional compartment syndrome (CECS). However, not all patients have demonstrated the same level of symptom improvement. Hypothesis: Specific patient variables will lead to enhanced functional improvement after fasciotomy for CECS of the lower extremity. Study Design: Case series. Level of Evidence: Level 4. Methods: A review of patients undergoing fasciotomy of the lower extremity for treatment of CECS by a single surgeon from 2009 to 2017 was performed. Pre- and postoperative measures of Foot and Ankle Ability Measure–Sports subscale (FAAM–Sports), FAAM–Sports Single Assessment Numeric Evaluation (SANE), and visual analog scale (VAS) for pain during sporting activities were collected at a minimum of 12 months postoperatively. The primary outcomes of change in FAAM-Sports, FAAM-Sports SANE, and VAS during sporting activities were calculated by taking the difference of post- and preoperative scores. Generalized multiple linear regression analyses was performed to determine independent predictors of functional and pain improvement. Results: A total of 61 patients (58% response rate) who underwent 65 procedures were included in this study, with postoperative outcome measures obtained at mean duration of 57.9 months (range, 12-115 months) after surgery. Patients had a mean ± SD improvement in FAAM-Sports of 40.4 ± 22.3 points ( P < 0.001), improvement in FAAM-Sports SANE of 57.3 ± 31.6 points ( P < 0.001), and reduction of VAS pain of 56.4 ± 31.8 points ( P < 0.001). Multiple linear regression analysis revealed deep posterior compartment involvement, younger age, a history of depression, and male sex to be significant independent predictors of enhanced improvement after fasciotomy. Conclusion: Fasciotomy is an effective treatment of CECS, with our study identifying certain patient variables leading to greater functional improvement. Clinical Relevance: Male patients, younger patients, patients with depression, and patients with deep posterior compartment involvement may serve to benefit more with fasciotomies for treatment of CECS.
Urinary sodium potassium ratio is associated with clinical success after adrenalectomy in patients with unilateral primary aldosteronism
Authors: Lee Ming-Jse , Sun Chiao-Yin , Lu Ching-Chu , Chang Yuan-Shian , Pan Heng-Chih , Lin Yen-Hung , Wu Vin-Cent , Chueh Jeff S. 
Published: February 2021

Background: The urinary sodium potassium (NaK) ratio is associated with dietary sodium and potassium intake and blood pressure, and it also reflects the activity of aldosterone. Herein we evaluated the value of the urinary NaK ratio in predicting the surgical outcomes of patients with unilateral primary aldosteronism (uPA). Methods: This non-concurrent prospective cohort study was conducted from 2011 to 2017 and included 241 uPA patients who had undergone adrenalectomy. Predictors of successful clinical outcomes were analyzed using logistic regression. Results: Among the 241 uPA patients, 197 (81.7%) achieved clinical complete or partial success. A urinary sodium potassium ratio <3 (odds ratio (OR): 2.5; 95% confidence interval (CI): 1.2–5.4; p = 0.015), body mass index <25 kg/m2 (OR: 2.82; 95% CI: 1.31–6.06; p = 0.008), renin <1 ng/mL/h (OR: 2.51; 95% CI: 1.01–6.21; p = 0.047) and mean preoperative blood pressure >115 mmHg (OR: 5.02; 95% CI: 2.10–11.97; p < 0.001) could predict clinical success after adrenalectomy. Furthermore, higher pre-treatment plasma aldosterone (OR: 1.014; 95% CI 1.005–1.024; p = 0.002) or lower serum potassium (OR: 0.523; 95% CI: 0.328–0.836; p = 0.007) were correlated with lower urinary NaK ratio (<3), and log urinary NaK ratio was positively correlated with serum C-reactive protein ( β value 2.326; 95% CI 0.029–4.623; p = 0.047). Conclusions: uPA patients with a lower urinary NaK ratio, due to high plasma aldosterone and low serum potassium concentrations, were more likely to have clinical success after adrenalectomy. uPA patients with a higher urinary NaK ratio were associated with more severe inflammatory status, and possibly more resistant hypertension post-operatively.
A cross-sectional survey of COVID-19 preparedness in governmental hospitals of North-West Ethiopia
Authors: Tiruneh Abebe , Yetneberk Tikuneh , Eshetie Denberu , Chekol Bassazinew , Gellaw Moges 
Published: February 2021

Introduction: The novel coronavirus was first reported in December 2019, from Wuhan, China, and it has been declared as a pandemic by World Health Organization on 7 January 2020, and from that time till now the disease transmitted across the world. Hospitals need to be prepared for the overwhelming COVID-19 cases in their respective hospitals. Objectives: The objective of this study was to assess the level of hospital preparedness for COVID-19 in South Gondar Zone Governmental Hospitals, 2020. Methods: The institutionally based survey was conducted in South Gondar Zone Hospitals from 20 July to 25 July 2020. We used the World Health Organization preparedness checklist for COVID-19, and the checklist has three options for eight hospitals (not started, in progress, and started), so each hospital evaluated out of 208 points (104 items × 2) to assess each hospital their preparedness based on the checklist. Statistical Package for the Social Sciences, Version 21, is used for the analysis of the data. We used descriptive statistics and explained by using text and tables. Results: We evaluated all eight hospitals in these zone hospitals and only one hospital was in an acceptable level of preparation (>146 points), three hospitals were in an insufficient level of preparation (73–145 points), and the other four hospitals were grouped under the unacceptable level of preparation (<72 points) for COVID-19. And in all hospitals, there was no laboratory diagnostic method and treatment center for the COVID-19 virus. Conclusion: From the level of COVID-19 pandemic preparation from eight hospitals, only one hospital reaches the level of an acceptable level of preparedness. Mobilizing the community and other stakeholders to equip the hospital with resources and prioritization is recommended to mitigate the impact of COVID-19.
Addressing Social Determinants of Health Identified by Systematic Screening in a Medicaid Accountable Care Organization: A Qualitative Study
Authors: Browne Julia , Mccurley Jessica L. , Fung Vicki , Levy Douglas E. , Clark Cheryl R. , Thorndike Anne N. 
Published: February 2021

Introduction/Objectives: Systematic screening for social determinants of health (SDOH), such as food and housing insecurity, is increasingly implemented in primary care, particularly in the context of Accountable Care Organizations (ACO). Despite the importance of developing effective systems for SDOH resource linkage, there is limited research examining these processes. The objective of the study was to explore facilitators and barriers to addressing SDOH identified by systematic screening in a healthcare system participating in a Medicaid ACO. Methods: This qualitative case study took place between January and March 2020. Semi-structured interviews were conducted with fifteen staff (8 community resource staff and 7 managers) from community health centers and hospitals affiliated with a large healthcare system. Interviews were transcribed, coded, and analyzed using the Framework Method. Results: Facilitators for addressing SDOH included maintaining updated resource lists, collaborating with community organizations, having leadership buy-in, and developing a trusting relationship with patients. Barriers to addressing SDOH included high caseloads, time constraints, inefficiencies in tracking, lack of community resources, and several specific patient characteristics. Further, resource staff expressed distress associated with having to communicate to patients that they were unable to address certain needs. Conclusions: Health system, community, and individual-level facilitators and barriers should be considered when developing programs for addressing SDOH. Specifically, the psychological burden on resource staff is an important and underappreciated factor that could impact patient care and lead to staff burnout.
IFT46 Expression in the Nasal Mucosa of Primary Ciliary Dyskinesia Patients: Preliminary Study
Authors: Mata Manuel , Zurriaga Javier , Milian Lara , Reula Ana , Armengot Miguel , Ruiz-Sauri Amparo , Carda Carmen 
Published: February 2021

Background Primary ciliary dyskinesia (PCD) is characterised by an imbalance in mucociliary clearance leading to chronic respiratory infections. Cilia length is considered to be a contributing factor in cilia movement. Recently, IFT46 protein has been related to cilia length. Therefore, this work aims to study IFT46 expression in a PCD patients cohort and analyse its relationship with cilia length and function, as it was not previously described. Materials and methods The expression of one intraflagellar transport ( IFT46) and two regulating ciliary architecture ( FOXJ1 and DNAI2) genes, as well as cilia length of 27 PCD patients, were measured. PCD patients were diagnosed based on clinical data, and cilia function and ultrastructure. Gene expression was estimated by real-time RT-PCR and cilia length by electron microscopy in nasal epithelium biopsies. Results and conclusions: While IFT46 expression was only diminished in patients with short cilia, FOXJ1, and DNAI2 expression were reduced in all PCD patient groups compared to controls levels. Among the PCD patients, cilia were short in 44% (5.9 ± 0.70 µm); nine of these (33% from the total) patients’ cilia also had an abnormal ultrastructure. Cilia length was normal in 33% of patients (6.4 ± 0.39 µm), and only three patients’ biopsies indicated decreased expression of dynein.
Impacts of ecosystem vitality on ASEAN’s agricultural exports: A System Generalized Method of Moments approach
Authors: Doanh Nguyen Khanh , Quynh Nguyen Ngoc , Heo Yoon 
Published: February 2021

This study examined the impact of the Association of Southeast Asian Nations (ASEAN)’s ecosystem vitality (EV) on its agricultural exports to the rest of the world. Using a sample of the six major ASEAN countries (ASEAN-6) (including Indonesia, Malaysia, Philippines, Singapore, Thailand, and Vietnam) and their 72 trading partners for the period 2007–2016, we found robust evidence of a positive relationship between the quality of EV and the volume of agricultural exports. At the sectoral level, the quality of EV had the most substantial effects on the ASEAN’s exports of SITC-0 (food and live animals) and exerted the least impact on the ASEAN’s exports of SITC-2 (crude materials, inedible, except fuels). This empirical evidence implies that natural resource-intensive products are more sensitive to the quality of EV. At the country level, EV has the most potent effect on the ASEAN’s agricultural exports to high-income countries and the least impact on the ASEAN’s agricultural exports to low-income countries. To promote agricultural exports, especially to high-income countries, our empirical results suggest that ASEAN countries need to build specific and effective plans for conservation of environment and management of sustainable ecosystems. JEL Classification: C33, F14, and Q56
Progression of Allograft Extrusion in Both the Coronal and Sagittal Planes at Midterm Follow-up After Medial Meniscal Allograft Transplant
Authors: Kim Hanwook , Bin Seong-Il , Kim Jong-Min , Lee Bum-Sik , Sohn Dong-Wook 
Published: February 2021

Background: Although many studies have examined allograft extrusion after medial meniscal allograft transplant (MMAT), it is unclear whether allograft extrusion progresses at midterm follow-up. Hypothesis: After MMAT, allograft extrusion would not progress during the midterm follow-up period. Study Design: Case series; Level of evidence, 4. Methods: A total of 30 patients who underwent MMAT between December 1996 and March 2016 were enrolled. Allograft extrusion was measured on magnetic resonance imaging scans obtained at 6 weeks, 1 year, and 3 to 7 years postoperatively. In the coronal plane, the absolute allograft extrusion and relative percentage of extrusion were measured. In the sagittal plane, the absolute and relative anterior cartilage meniscal distance and posterior cartilage meniscal distance were measured. The joint-space width (JSW) on radiographic Rosenberg view was measured at 3 time points. The axial alignment was measured preoperatively and at the midterm follow-up. Results: In the coronal plane, there were no significant differences in absolute and relative coronal extrusions between 6 weeks and 1 year postoperatively; however, the values were significantly increased at midterm follow-up compared with both of the earlier follow-up periods. Similarly, in the sagittal plane, the mean absolute and relative anterior and posterior cartilage meniscal distances were not significantly different between 6 weeks and 1 year postoperatively but showed significant increases at midterm follow-up compared with both of the earlier follow-up periods. The mean preoperative axial alignment showed a positive correlation with the delta value of relative percentage of extrusion in the coronal plane ( r = 0.378; P = .036). The mean JSW was 4.42 ± 0.88 mm preoperatively, 4.30 ± 0.83 mm at 1-year follow-up, and 3.96 ± 1.06 mm at the midterm follow-up. No significant difference was found between the preoperative and postoperative 1-year values, but the mean JSW was significantly decreased at midterm follow-up compared with both of the other time points ( P = .001 for both). Conclusion: Allograft extrusion did not progress until 1 year after MMAT; however, by midterm follow-up, extrusion had progressed in both the coronal and the sagittal planes. Preoperative axial alignment showed a positive correlation with allograft extrusion in the coronal plane.
A computer-game-based rehabilitation platform for individuals with fine and gross motor upper extremity deficits post-stroke (CARE fOR U) – Protocol for a randomized controlled trial
Authors: Gandhi Dorcas BC , Pandian Jeyaraj D , Szturm Tony , Kanitkar Anuprita , Kate Mahesh P , Bhanot Komal 
Published: February 2021

Background & purpose Activity-based neuroplasticity and re-organization leads to motor learning via replicating real-life movements. Increased repetition of such movements has growing evidence over last few decades. In particular, computer-game-based rehabilitation is found to be effective, feasible and acceptable for post-stroke upper limb deficits. Our study aims to evaluate the feasibility and effectiveness of 12 weeks of computer-game-based rehabilitation platform (GRP) on fine and gross motor skills post-stroke in India. Methods Through this trial we will study the effect of adjunctive in-hospital GRP (using a motion-sensing airmouse with off-the-shelf computer games) in 80 persons with subacute stroke, for reduction of post-stroke upper limb deficits in a single-centre prospective Randomized Open, Blinded End- point trial when compared to conventional therapy alone. Results We intend to evaluate between-group differences using Wolf Motor Function test, Stroke Specific Quality of Life, and GRP assessment tool. Feasibility will be assessed via recruitment rates, adherence to intervention periods, drop-out rate and qualitative findings of patient experience with the intervention. Conclusion The CARE FOR U trial is designed to test the feasibility and effectiveness of a computer-game based rehabilitation platform in treating upper limb deficits after stroke. In case of positive findings GRP can be widely applicable for stroke populations needing intensive and regular therapy with supervision.