bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Peroneus longus autograft a better alternative to the Hamstring autograft for anterior cruciate ligament reconstruction? – A randomised control study
Authors: Vijay C. , Santosh M.S. , Avinash Chandra , Adarsh T.
Published: April 2022

Purpose

The anterior cruciate ligament in the knee is commonly prone to injuries. Reconstruction of this ligament with hamstring tendon has been time-tested but peroneus longus autograft is also gaining popularity. However, very limited literature is available comparing the two grafts. This study aims to compare the functional outcome and donor site morbidity between hamstrings and peroneus longus autograft in anterior cruciate ligament reconstruction.

Methods

A prospective randomised study was conducted on 45 patients, who underwent anterior cruciate ligament reconstruction. Patients were assigned into Hamstring group and the Peroneus longus group. Functional outcome was assessed using Lysholm score and Modified Cincinnati scores for the knee joint and American Orthopedics Foot and Ankle Scoring for ankle joint. Donor site morbidity was assessed by measuring flexion and extension strength of the knee and plantar flexion and eversion strength of the ankle by handheld dynamometer preoperatively and postoperatively at 6 months and 1 year follow up.

Results

Functional outcome of the knee showed significant improvement in peroneus longus group (p-value 0.002) compared to hamstring group. Even though there was minimal reduction in functional outcome of the ankle at 6 months follow-up in peroneus longus group, it improved at one year follow-up. While assessing the donor site morbidity at the knee joint, knee flexion strength showed improvement in the group (p-value 0.02) but reduced in the hamstring group where the hamstring tendon was harvested. Knee extension strength in the hamstring group scored marginally better than the peroneus longus group, which was not statistically significant (p-value 0.5).

Conclusion

Autologous peroneus longus tendon can be used as a graft of choice in anterior cruciate ligament reconstruction which showed promising results without compromising on the ankle function. Its usage as an alternative source of the graft may be more useful in multi-ligament injuries of the knee joint.
Negotiating transboundary crises in higher education: Tsinghua University’s shift to online learning during the COVID-19 pandemic
Authors: Nicol Stephanie , Bice Sara
Published: April 2022

The COVID-19 pandemic posed a major challenge for education leaders and policymakers across the globe. This paper discusses the experience of Tsinghua University’s shift to fully online learning, as the first major university in the world to move all courses online in response to the 2020 pandemic. The article introduces the Institutional Resilience in Higher Education Framework to articulate the factors that drive quality education during times of crisis. The article explores the shift to online learning in the context of pandemic as transboundary crisis and details Tsinghua’s online learning emergency response to distil lessons learnt and identify emerging best practices for further online learning implementation. It extrapolates broader lessons about university response to transboundary crises and highlights the importance of effective crisis management, institutional resilience and leadership for delivering quality higher education in emergencies and beyond.
Assessment of the Quality of Current American Dental Association Clinical Practice Guidelines
Authors: London S.D. , Chamut S. , Fontelo P. , Iafolla T. , Dye B.A.
Published: April 2022

Introduction:

The American Dental Association (ADA) defines evidence-based dentistry (EBD) as “an approach to oral healthcare that requires the judicious integration of systematic assessments of clinically relevant scientific evidence, relating to the oral and medical condition and history, with the dentist’s clinical expertise and the patient’s treatment needs and preferences.” Clinical practice guidelines (CPGs) are statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options. Therefore, ADA CPGs are the most rigorous examples of EBD to inform clinical practice. CPGs should be of the highest level of quality to ensure the appropriateness and timeliness of clinical recommendations.

Objectives:

The aim of this study was to measure the methodological rigor and transparency of the ADA CPGs.

Methods:

Each ADA CPG was appraised by 4 independent assessors using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Quantitative quality scores were obtained for 6 domains and overall quality. In addition, assessors provided a qualitative analysis by providing comments for each item and an appraisal of the full recommendation.

Results:

A quality score of 75% was used as the threshold for high-quality guidelines. Using this metric, 6 of the current 10 current ADA CPGs were considered to be of high quality, 1 was slightly below the quality threshold, and 3 were considered marginal. Even among those evaluated to be high quality in overall assessment, certain domains did not reach the quality threshold of 75%.

Conclusion:

Overall, the ADA CPGs collectively provide high-quality guidance for the clinician. While the AGREE appraisal guidelines have been used in CPG development since 2016, there is still room for improvement in certain domains (i.e., stakeholder involvement, rigor of development, applicability, and editorial independence).

Knowledge Transfer Statement:

The results of this study summarize the methodological rigor and transparency of the 10 current ADA clinical practice guidelines. Since adoption of AGREE standards (2016), CPGs have been uniformly of high quality. The quality of older CPGs was somewhat lower but overall deemed acceptable. Thus, ADA CPGs may be used with confidence to inform practitioners of treatment options supported by rigorous evidence-based dentistry standards. However, there is still room for improvement in methodological quality.
Stewardship practice and the performance of citizenship: Greening tree-pits in the streets of Berlin
Authors: Lachmund Jens
Published: April 2022

Hands-on activities of shaping and maintaining urban public green spaces, in short, “stewardship,” have become a flourishing field of civic engagement. It is the aim of this article to find out how citizenship is enacted in the everyday practice of stewardship, and how such an analysis can benefit from theories of “material participation” and “practice.” It explores this theme through a case study of the greening of tree-pits in Berlin. The article asks: (1) how people, through their doing of stewardship, engage with the tangible places that they take care of, and (2) how connections between stewardship, its focal places, and other practices shape and sustain wider public concerns. Thereby, it identifies three intersecting and materially grounded “civic nexuses of practices,” which each imply specific constructions of citizenship: civic neighboring, managed volunteering, and political mobilization. It explores how each of these nexuses emerges from the convergence of practices around the tree-pit, and probes the tensions and conflicts that they entail. In contrast to authors who have either cherished stewardship as a form of citizen empowerment, or, in line with Foucauldian governmentality studies, as the formation of governable citizen-subjects, the article emphasizes the politically ambiguous dynamics through which stewards practice their citizenship.
Mechanisms of implementation: An appraisal of causal pathways presented at the 5th biennial Society for Implementation Research Collaboration (SIRC) conference
Authors: Vejnoska Sarah F. , Mettert Kayne , Lewis Cara C.
Published: April 2022

Background Implementation mechanisms are defined as processes or events through which implementation strategies operate to affect one or more implementation outcomes. Understanding the mechanisms through which implementation strategies work is critical to understanding how and why implementation efforts are successful, and to matching, tailoring, and optimizing implementation strategies. This study examined the content of abstracts included in the program for the 2019 Society for Implementation Research Collaboration (SIRC) conference to characterize the presence of data related to implementation strategy mechanisms and their larger causal pathways. Methods Trained coders reviewed all 205 accepted abstracts and extracted information regarding discrete implementation strategies, determinants of implementation, implementation mechanisms, service outcomes, and implementation outcomes. Theoretical articles were omitted from further analyses due to their inability to offer data related to implementation mechanisms. Results Of the 151 empirical studies included, only 11 (7.28%) reported studying mechanisms. Mechanisms were examined in projects utilizing 14 different implementation strategies. We were able to construct implementation causal pathways for just two implementation strategies, “assess for readiness and identify determinants,” representing information pulled from four different abstracts, and “create a learning collaborative,” with data pulled from just one abstract. Conclusions These findings indicate that, at least based on SIRC conference abstracts, the empirical investigation of implementation mechanisms remains understudied, highlighting the need for focused research on the study of mechanisms. Plain Language Summary Understanding the mechanisms through which implementation strategies work is critical to understanding how and why implementation efforts are successful. The study of implementation mechanisms may be used to optimize implementation strategy decisions. Investigations to date have not established causal pathways linking implementation strategies, mechanisms, barriers, and outcomes. This study examined abstracts included in the program for the 2019 Society for Implementation Research Collaboration (SIRC) conference. Trained coders reviewed all 205 accepted abstracts and extracted information to characterize the presence of data related to implementation strategy causal pathways. A minority of abstracts reported studying mechanisms. We were able to construct implementation causal pathways for just two implementation strategies, representing information pulled from five different abstracts all together. This highlights the need for focused research on the study of mechanisms.
Time–motion analysis of external facilitation for implementing the Collaborative Chronic Care Model in general mental health clinics: Use of an interval-based data collection approach
Authors: Kim Bo , Miller Christopher J. , Ritchie Mona J. , Smith Jeffrey L. , Kirchner JoAnn E. , Stolzmann Kelly , Connolly Samantha L. , Drummond Karen L. , Bauer Mark S.
Published: April 2022

Background: Facilitation is an effective strategy to implement evidence-based practices, often involving external facilitators (EFs) bringing content expertise to implementation sites. Estimating time spent on multifaceted EF activities is complex. Furthermore, collecting continuous time–motion data for facilitation tasks is challenging. However, organizations need this information to allocate implementation resources to sites. Thus, our objectives were to conduct a time–motion analysis of external facilitation, and compare continuous versus noncontinuous approaches to collecting time–motion data. Methods: We analyzed EF time–motion data from six VA mental health clinics implementing the evidence-based Collaborative Chronic Care Model (CCM). We documented EF activities during pre-implementation (4–6 weeks) and implementation (12 months) phases. We collected continuous data during the pre-implementation phase, followed by data collection over a 2-week period (henceforth, “a two-week interval”) at each of three time points (beginning/middle/end) during the implementation phase. As a validity check, we assessed how closely interval data represented continuous data collected throughout implementation for two of the sites. Results: EFs spent 21.8 ± 4.5 h/site during pre-implementation off-site, then 27.5 ± 4.6 h/site site-visiting to initiate implementation. Based on the 2-week interval data, EFs spent 2.5 ± 0.8, 1.4 ± 0.6, and 1.2 ± 0.6 h/week toward the implementation’s beginning, middle, and end, respectively. Prevalent activities were preparation/planning, process monitoring, program adaptation, problem identification, and problem-solving. Across all activities, 73.6% of EF time involved email, phone, or video communication. For the two continuous data sites, computed weekly time averages toward the implementation’s beginning, middle, and end differed from the interval data’s averages by 1.0, 0.1, and 0.2 h, respectively. Activities inconsistently captured in the interval data included irregular assessment, stakeholder engagement, and network development. Conclusions: Time–motion analysis of CCM implementation showed initial higher-intensity EF involvement that tapered. The 2-week interval data collection approach, if accounting for its potential underestimation of irregular activities, may be promising/efficient for implementation studies collecting time–motion data.
Research-to-Resource: Peer-Assisted Learning in the Music Program
Authors: Saccardi David J.
Published: April 2022

Music educators are exploring ways to implement peer-assisted learning in their classrooms in an effort to foster a more inclusive and collaborative learning environment. By observing students in peer teaching roles, teachers can gain information related to individual levels of social appropriateness as well as skill comprehension, and additional individual repetitions of skill sequences can occur during a class period. In this research to resource article, I discuss research literature related to academic, social, and emotional benefits of peer-assisted learning. Two prominent approaches, cross-age peer tutoring and reciprocal peer tutoring, are outlined and the merits of each approach discussed. Strategies for successfully implementing peer-assisted learning in the music classroom are presented. Intelligently preparing peer-assisted learning and objectively assessing the outcome could allow this teaching and learning strategy to become a valuable part of a music teacher’s classroom routine and instructional toolkit.
A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design
Authors: Zhang Hui , He Chuan , Jiang Fanming , Cao Shuang , Zhao Bin , Ding Haibo , Dong Tao , Han Xiaoxu , Shang Hong
Published: April 2022

Background

Identifying immunogens which can elicit effective T cell responses against human immunodeficiency virus type 1 (HIV-1) is important for developing a T-cell based vaccine. It has been reported that human leukocyte antigen (HLA)-B*13-restricted T-cell responses contributed to HIV control in subtype B′ and C infected individuals. However, the kinetics of B*13-restricted T-cell responses, viral evolution within epitopes, and the impact on disease progression in CRF01_AE subtype HIV-1-infected men who have sex with men (MSM) are not known.

Results

Interferon-γ ELISPOT assays and deep sequencing of viral RNAs were done in 14 early HLA-B*13-positive CRF01_AE subtype HIV-1-infected MSM. We found that responses to RQEILDLWV (Nef106–114, RV9), GQMREPRGSDI (Gag226–236, GI11), GQDQWTYQI (Pol487–498, GI9), and VQNAQGQMV (Gag135–143, VV9) were dominant. A higher relative magnitude of Gag-specific T-cell responses, contributed to viral control, whereas Nef-specific T-cell responses were associated with rapid disease progression. GI11 (Gag) was conserved and strong GI11 (Gag)-specific T-cell responses showed cross-reactivity with a dominant variant, M228I, found in 3/12 patients; GI11 (Gag)-specific T-cell responses were positively associated with CD4 T-cell counts (R = 0.716, P = 0.046). Interestingly, the GI9 (Pol) epitope was also conserved, but GI9 (Pol)-specific T-cell responses did not influence disease progression (P > 0.05), while a D490G variant identified in one patient did not affect CD4 T-cell counts. All the other epitopes studied [VV9 (Gag), RQYDQILIEI (Pol113–122, RI10), HQSLSPRTL (Gag144–152, HL9), and RQANFLGRL (Gag429–437, RL9)] developed escape mutations within 1 year of infection, which may have contributed to overall disease progression. Intriguingly, we found early RV9 (Nef)-specific T-cell responses were associated with rapid disease progression, likely due to escape mutations.

Conclusions

Our study strongly suggested the inclusion of GI11 (Gag) and exclusion of RV9 (Nef) for T-cell-based vaccine design for B*13-positive CRF01_AE subtype HIV-1-infected MSM and high-risk individuals.
Overexpression of sesame polyketide synthase A leads to abnormal pollen development in Arabidopsis
Authors: Li Tianyu , Yang Yuanxiao , Liu Hongyan , Dossou Senouwa Segla Koffi , Zhou Fang , Zhou Ting , Zhao Yingzhong
Published: April 2022

Background

Sesame is a great reservoir of bioactive constituents and unique antioxidant components. It is widely used for its nutritional and medicinal value. The expanding demand for sesame seeds is putting pressure on sesame breeders to develop high-yielding varieties. A hybrid breeding strategy based on male sterility is one of the most effective ways to increase the crop yield. To date, little is known about the genes and mechanism underlying sesame male fertility. Therefore, studies are being conducted to identify and functionally characterize key candidate genes involved in sesame pollen development. Polyketide synthases (PKSs) are critical enzymes involved in the biosynthesis of sporopollenin, the primary component of pollen exine. Their in planta functions are being investigated for applications in crop breeding.

Results

In this study, we cloned the sesame POLYKETIDE SYNTHASE A (SiPKSA) and examined its function in male sterility. SiPKSA was specifically expressed in sesame flower buds, and its expression was significantly higher in sterile sesame anthers than in fertile anthers during the tetrad and microspore development stages. Furthermore, overexpression of SiPKSA in Arabidopsis caused male sterility in transgenic plants. Ultrastructural observation showed that the pollen grains of SiPKSA-overexpressing plants contained few cytoplasmic inclusions and exhibited an abnormal pollen wall structure, with a thicker exine layer compared to the wild type. In agreement with this, the expression of a set of sporopollenin biosynthesis-related genes and the contents of their fatty acids and phenolics were significantly altered in anthers of SiPKSA-overexpressing plants compared with wild type during anther development.

Conclusion

These findings highlighted that overexpression of SiPKSA in Arabidopsis might cause male sterility through defective pollen wall formation. Moreover, they suggested that SiPKSA modulates vibrant pollen development via sporopollenin biosynthesis, and a defect in its regulation may induce male sterility. Therefore, genetic manipulation of SiPKSA might promote hybrid breeding in sesame and other crop species.
Genome-wide TCP transcription factors analysis provides insight into their new functions in seasonal and diurnal growth rhythm in Pinus tabuliformis
Authors: Nie Yu-meng , Han Fang-xu , Ma Jing-jing , Chen Xi , Song Yi-tong , Niu Shi-Hui , Wu Harry X.
Published: April 2022

Background

Pinus tabuliformis adapts to cold climate with dry winter in northern China, serving as important commercial tree species. The TEOSINTE BRANCHED 1, CYCLOIDEA, and PROLIFERATING CELL FACTOR family(TCP)transcription factors were found to play a role in the circadian clock system in Arabidopsis. However, the role of TCP transcription factors in P. tabuliformis remains little understood.

Results

In the present study, 43 TCP genes were identified from P. tabuliformis genome database. Based on the phylogeny tree and sequence similarity, the 43 TCP genes were classified into four groups. The motif results showed that different subfamilies indeed contained different motifs. Clade II genes contain motif 1, clade I genes contain motif 1, 8, 10 and clade III and IV contain more motifs, which is consistent with our grouping results. The structural analysis of PtTCP genes showed that most PtTCPs lacked introns. The distribution of clade I and clade II on the chromosome is relatively scattered, while clade III and clade IV is relatively concentrated. Co-expression network indicated that PtTCP2, PtTCP12, PtTCP36, PtTCP37, PtTCP38, PtTCP41 and PtTCP43 were co-expressed with clock genes in annual cycle and their annual cycle expression profiles both showed obvious seasonal oscillations. PtTCP2, PtTCP12, PtTCP37, PtTCP38, PtTCP40, PtTCP41, PtTCP42 and PtTCP43 were co-expressed with clock genes in diurnal cycle. Only the expression of PtTCP42 showed diurnal oscillation.

Conclusions

The TCP gene family, especially clade II, may play an important role in the regulation of the season and circadian rhythm of P. tabuliformis. In addition, the low temperature in winter may affect the diurnal oscillations.
Comparison of left double lumen tube and y-shaped and double-ended bronchial blocker for one lung ventilation in thoracic surgery—a randomised controlled clinical trial
Authors: Risse Joachim , Szeder Karsten , Schubert Ann-Kristin , Wiesmann Thomas , Dinges Hanns-Christian , Feldmann Carsten , Wulf Hinnerk , Meggiolaro Karl Matteo
Published: April 2022

Background

Double lumen tube (DLT) intubation is the most commonly used technique for one lung ventilation. Bronchial blockers (BB) are an alternative, especially for difficult airways. The EZ-bronchial blocker (EZB) is an innovative y-shaped and double-ended device of the BB family.

Methods

A randomised, controlled trial was conducted in 80 patients undergoing elective thoracic surgery using DLT or EZB for one lung ventilation (German Clinical Trial Register DRKS00014816). The objective of the study was to compare the clinical performance of EZB with DLT. Primary endpoint was total time to obtain successful one lung ventilation. Secondary endpoints were time subsections, quality of lung collapse, difficulty of intubation, any complications during the procedure, incidence of objective trauma of the oropharynx and supraglottic space and intubation-related subjective symptoms.

Results

74 patients were included, DLT group (n = 38), EZB group (n = 36). Median total time to obtain one lung ventilation [IQR] in the DLT group was 234 s [207 to 294] versus 298 s [243 to 369] in the EZB group (P = 0.007). Median total time was relevantly influenced by different preparation times. Quality of lung collapse was equal in both groups, DLT group 89.5% were excellent vs. 83.3% in the EZB group (P = 0.444). Inadequate lung collapse in five patients of the EZB group resulted in unsuccessful repositioning attempts and secondary DLT placement. Endoscopic examinations revealed significantly more carina trauma (P = 0.047) and subglottic haemorrhage (P = 0.047) in the DLT group. Postoperative subjective symptoms (sore throat, hoarseness) were more common in the DLT group, as were speech problems.

Conclusions

Using EZB prima facie results in prolonged time to obtain one lung ventilation with equal quality of lung collapse for the thoracic surgeon. If preparation times are omitted in the analysis, the time difference is statistically and clinically not relevant. Our data showed only little evidence for reducing objective airway trauma as well as subjective complaints. In summary both procedures were comparable in terms of times and clinical applicability. Therefore decisions for DLT or EZB should depend more on individual experience, in-house equipment and the individual patient, than on any times that are neither clinically significant nor relevant.

Trial registration

German Clinical Trial Register DRKS00014816, prospectively registered on 07.06.2018
Observational study on chest pain during the Covid-19 pandemic: changes and characteristics of visits to a Norwegian emergency department during the lockdown
Authors: Grande Mikkel , Bjørnsen Lars Petter , Næss-Pleym Lars Eide , Laugsand Lars Erik , Grenne Bjørnar
Published: April 2022

Background

Following the spread of the Covid-19 pandemic in 2020, reports emerged on decreasing emergency department (ED) visits in many countries. Patients experiencing chest pain was no exception. The aim of the current study was to describe how the Covid-19 pandemic and the subsequential lockdown impacted the chest pain population in a Norwegian ED.

Methods

All patients presenting to the ED with chest pain during the study period were included. Data were collected retrospectively from the time period January 6th to August 30th, 2020, and compared to the corresponding period in 2019, assessing variations in the number of ED visits, severity, gender, and age.

Results

Fewer patients with chest pain were seen in the ED following the national lockdown in Norway, compared to the corresponding 2019 period (week 13: 38% fewer; weeks 11–27: 16% fewer). By week 28, the rate normalized compared to 2019 levels. There was a relative increase in lower acuity patients among these patients, while fewer moderate acuity patients were seen. During the initial period following lockdown, the median age was lower compared to the corresponding 2019 period (58 years (IQR 25) vs 62 years (IQR 24), respectively). Admissions due to acute coronary syndromes (ACS) remained proportionally stable.

Conclusions

Succeeding the Covid-19 outbreak and the subsequent national lockdown in Norway, fewer chest pain patients presented to the ED. Paradoxically, the patients seemed to be less severely ill and were on average younger compared to 2019 data. However, the proportion of patients admitted with ACS was stable during this period. This could imply that some patients may have failed to seek medical advice despite experiencing a myocardial infarction.
Retirement as a predictor of physical functioning trajectories among older businessmen
Authors: Haapanen Markus J. , Strandberg Timo E. , Törmäkangas Timo , von Bonsdorff Monika E. , Strandberg Arto Y. , von Bonsdorff Mikaela B.
Published: April 2022

Background

Associations between retirement characteristics and consequent physical functioning (PF) are poorly understood, particularly in higher socioeconomic groups, where postponing retirement has had both positive and negative implications for PF.

Methods

Multiple assessments of PF, the first of which at the mean age of 73.3 years, were performed on 1709 men who were retired business executives and managers, using the RAND-36/SF-36 instrument, between 2000 and 2010. Questionnaire data on retirement age and type of pension was gathered in 2000. Five distinct PF trajectories were created using latent growth mixture modelling. Mortality- and covariate-adjusted multinomial regression models were used to estimate multinomial Odds Ratios (mOR) on the association between retirement characteristics and PF trajectories.

Results

A one-year increase in retirement age was associated with decreased likelihood of being classified in the ‘consistently low’ (fully adjusted mOR = 0.82; 95%CI = 0.70, 0.97; P = 0.007), ‘intermediate and declining’ (mOR = 0.89; 95%CI = 0.83, 0.96; P = 0.002), and ‘high and declining’ (mOR = 0.92; 95%CI = 0.87, 0.98; P = 0.006) trajectories, relative to the ‘intact’ PF trajectory. Compared to old age pensioners, disability pensioners were more likely to be classified in the ‘consistently low’ (mOR = 23.77; 95% CI 2.13, 265.04; P = 0.010), ‘intermediate and declining’ (mOR = 8.24; 95%CI = 2.58, 26.35; P < 0.001), and ‘high and declining’ (mOR = 2.71; 95%CI = 1.17, 6.28; P = 0.020) PF trajectories, relative to the ‘intact’ PF trajectory.

Conclusions

Among executives and managers, older age at retirement was associated with better trajectories of PF in old age. Compared to old age pensioners, those transitioning into disability and early old age pensions were at risk of having consistently lower PF in old age.
Sputum lipoarabinomannan (LAM) as a biomarker to determine sputum mycobacterial load: exploratory and model-based analyses of integrated data from four cohorts
Authors: Jones Aksana , Saini Jay , Kriel Belinda , Via Laura E. , Cai Yin , Allies Devon , Hanna Debra , Hermann David , Loxton Andre G. , Walzl Gerhard , Diacon Andreas H. , Romero Klaus , Higashiyama Ryo , Liu Yongge , Berg Alexander
Published: April 2022

Background

Despite the high global disease burden of tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb) infection, novel treatments remain an urgent medical need. Development efforts continue to be hampered by the reliance on culture-based methods, which often take weeks to obtain due to the slow growth rate of Mtb. The availability of a “real-time” measure of treatment efficacy could accelerate TB drug development. Sputum lipoarabinomannan (LAM; an Mtb cell wall glycolipid) has promise as a pharmacodynamic biomarker of mycobacterial sputum load.

Methods

The present analysis evaluates LAM as a surrogate for Mtb burden in the sputum samples from 4 cohorts of a total of 776 participants. These include those from 2 cohorts of 558 non-TB and TB participants prior to the initiation of treatment (558 sputum samples), 1 cohort of 178 TB patients under a 14-day bactericidal activity trial with various mono- or multi-TB drug therapies, and 1 cohort of 40 TB patients with data from the first 56-day treatment of a standard 4-drug regimen.

Results

Regression analysis demonstrated that LAM was a predictor of colony-forming unit (CFU)/mL values obtained from the 14-day treatment cohort, with well-estimated model parameters (relative standard error ≤ 22.2%). Moreover, no changes in the relationship between LAM and CFU/mL were observed across the different treatments, suggesting that sputum LAM can be used to reasonably estimate the CFU/mL in the presence of treatment. The integrated analysis showed that sputum LAM also appears to be as good a predictor of time to Mycobacteria Growth Incubator Tube (MGIT) positivity as CFU/mL. As a binary readout, sputum LAM positivity is a strong predictor of solid media or MGIT culture positivity with an area-under-the-curve value of 0.979 and 0.976, respectively, from receiver-operator curve analysis.

Conclusions

Our results indicate that sputum LAM performs as a pharmacodynamic biomarker for rapid measurement of Mtb burden in sputum, and thereby may enable more efficient early phase clinical trial designs (e.g., adaptive designs) to compare candidate anti-TB regimens and streamline dose selection for use in pivotal trials.

Trial registration NexGen EBA study (NCT02371681)
Serum anti-Müllerian hormone levels are associated with early miscarriage in the IVF/ICSI fresh cycle
Authors: Liu Xin , Han Ying , Wang Xinyan , Zhang Yunshan , Du Aijun , Yao Ruqiang , Lv Jiabei , Luo Haining
Published: April 2022

Background

Anti-Müllerian hormone (AMH) is used as a biomarker to estimate ovarian reserve. The relationship between AMH and early miscarriage of in vitro fertilization (IVF) is still inconclusive. This study aimed to explore whether serum AMH levels are associated with early miscarriage rates after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) with fresh embryo transfer (ET).

Methods

This retrospective cohort study included 2246 patients undergoing their first oocyte retrievals for IVF/ICSI with fresh embryos transferred to Tianjin Central Hospital of Gynecology Obstetrics between May 2018 and March 2020. The serum AMH levels of the patients were measured within 12 months before the IVF/ICSI cycles. All women were divided into a low-AMH group, medium-AMH group and high-AMH group. Binary logistic regression was applied to confirm whether the serum AMH level was associated with the risk of early miscarriage independent of potential confounders, such as age, body mass index (BMI), duration of infertility, main diagnosis, history of internal medicine diseases, number of oocytes retrieved and high-quality embryo rate.

Results

The early miscarriage rate was significantly lower in the medium-AMH group than in either the low-AMH or high-AMH group among young (< 35 years) women (P = 0.015). In women above 35 years of age, the early miscarriage rates in the three AMH groups were not significantly different. Young women with high serum AMH levels had a significantly higher risk of early miscarriage regardless of age or other potential confounders (adjusted odds ratio (OR) 2.382, 95% confidence interval (CI) 1.246 to 4.553, P = 0.009). The results remained similar after restricting the analysis to women without polycystic ovary syndrome (PCOS).

Conclusions

With a high AMH level, young women had a higher risk of early miscarriage than women with a medium AMH level in their first IVF/ICSI treatment. In young women, serum AMH levels were independently associated with the risk of early miscarriage after IVF-ET treatment. Serum AMH levels might be a valuable marker to estimate the risk of early miscarriage. It is worth noting to the clinical value of AMH.
Single fraction ablative preoperative radiation treatment for early-stage breast cancer: the CRYSTAL study – a phase I/II clinical trial protocol
Authors: Zerella Maria Alessia , Zaffaroni Mattia , Ronci Giuseppe , Dicuonzo Samantha , Rojas Damaris Patricia , Morra Anna , Fodor Cristiana , Rondi Elena , Vigorito Sabrina , Botta Francesca , Cremonesi Marta , Garibaldi Cristina , Penco Silvia , Galimberti Viviana Enrica , Intra Mattia , Gandini Sara , Barberis Massimo , Renne Giuseppe , Cattani Federica , Veronesi Paolo , Orecchia Roberto , Jereczek-Fossa Barbara Alicja , Leonardi Maria Cristina
Published: April 2022

Background

Breast-conserving surgery (BCS) and whole breast radiation therapy (WBRT) are the standard of care for early-stage breast cancer (BC). Based on the observation that most local recurrences occurred near the tumor bed, accelerated partial breast irradiation (APBI), consisting of a higher dose per fraction to the tumor bed over a reduced treatment time, has been gaining ground as an attractive alternative in selected patients with low-risk BC. Although more widely delivered in postoperative setting, preoperative APBI has also been investigated in a limited, though increasing, and number of studies. The aim of this study is to test the feasibility, safety and efficacy of preoperative radiotherapy (RT) in a single fraction for selected BC patients.

Methods

This is a phase I/II, single-arm and open-label single-center clinical trial using CyberKnife. The clinical investigation is supported by a preplanning section which addresses technical and dosimetric issues. The primary endpoint for the phase I study, covering the 1st and 2nd year of the research project, is the identification of the maximum tolerated dose (MTD) which meets a specific target toxicity level (no grade 3–4 toxicity). The primary endpoint for the phase II study (3rd to 5th year) is the evaluation of treatment efficacy measured in terms of pathological complete response rate.

Discussion

The study will investigate the response of BC to the preoperative APBI from different perspectives. While preoperative APBI represents a form of anticipated boost, followed by WBRT, different are the implications for the scientific community. The study may help to identify good responders for whom surgery could be omitted. It is especially appealing for patients unfit for surgery due to advanced age or severe co-morbidities, in addition to or instead of systemic therapies, to ensure long-term local control. Moreover, patients with oligometastatic disease synchronous with primary BC may benefit from APBI on the intact tumor in terms of tumor progression free survival. The study of response to RT can provide useful information about BC radiobiology, immunologic reactions, genomic expression, and radiomics features, to be tested on a larger scale.

Trial registration

The study was prospectively registered at clinicaltrials.gov (NCT04679454).
Intraepithelial lymphocytes are indicators of better prognosis in surgically resected endometrioid-type endometrial carcinomas at early and advanced stages
Authors: Kono-Sato Takako , Miyai Kosuke , Yamagishi Yoji , Miyamoto Morikazu , Takano Masashi , Matsukuma Susumu , Sato Kimiya , Tsuda Hitoshi
Published: April 2022

Background

Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) may be useful prognostic indicators in endometrial cancer. However, standardized assessment methods and the prognostic roles of these cells in different stage groups are unclear.

Methods

Formalin-fixed paraffin-embedded tissue samples of 107 endometrioid-type endometrial carcinomas (EECs) comprising 60 stage IB and 47 stage IIIC or IVB cases were evaluated. CD3+ TILs, CD8+ TILs, CD68+ TAMs, and CD163+ TAMs were detected by immunohistochemistry, and their densities were evaluated by semiquantitative and quantitative methods. TILs within tumor epithelial cell nests (E-TILs) and those within the stroma at the invasive front (S-TILs) were evaluated separately for CD3+ and CD8+ cells. The “TIL score” was defined as the sum of semiquantitative scores of CD3+ E-TILs, CD3+ S-TILs, CD8+ E-TILs, and CD8+ S-TILs. For TAMs, the area of CD68+ and CD163+ cells in the invasive margin were semiquantitatively and quantitatively evaluated. Clinicopathological and prognostic implications of TILs and TAMs in stage IB and IIIC/IVB EECs were examined by Cox univariate and multivariate analyses.

Results

By Cox univariate analyses, semiquantitatively low CD3+ E-TILs, low CD8+ E-TILs, and low “TIL score” were significantly correlated with worse prognosis in stage IB patients (P = 0.011, 0.040, and 0.039, respectively). Likewise, low CD3+ E-TILs and low CD8+ E-TILs, by both semiquantitative (P = 0.011 and 0.0051) and quantitative evaluations (P < 0.0001, and P = 0.0015) and low “TIL score” (P = 0.020) were significantly correlated with worse prognosis in stage IIIC/IVB patients. By Cox multivariate analyses, semiquantitatively low CD3+ E-TILs and low CD8+ E-TILs, low “TIL score”, and quantitatively low CD3+ E-TILs and low CD8+ E-TILs were independent worse prognostic factors in stage IIIC/IVB (P = 0.0011, 0.0053, 0.012, < 0.0001, and < 0.0001, respectively). CD68+ or CD163+ TAMs were not correlated with prognosis in any patients.

Conclusions

Both semiquantitatively and quantitatively low E-TILs, are correlated with worse prognosis in both early and advanced stage patients with EECs. In particular, CD3+ E-TILs and CD8+ E-TILs are potentially useful prognostic markers in patients with EEC regardless of the stage.
FIRE-9 – PORT / AIO-KRK-0418: a prospective, randomized, open, multicenter Phase III trial to investigate the efficacy of adjuvant/additive chemotherapy in patients with definitely-treated metastatic colorectal cancer
Authors: Raschzok Nathanael , Stintzing Sebastian , Heinemann Volker , Rauch Geraldine , Ricke Jens , Guckenberger Matthias , Kurreck Annika , Alig Annabel H. S. , Stahler Arndt , Bullinger Lars , Schmelzle Moritz , Schöning Wenzel , Lurje Georg , Krenzien Felix , Haase Oliver , Rau Beate , Gebauer Bernhard , Sauer Igor M. , Pratschke Johann , Modest Dominik P.
Published: April 2022

Background

Additive/adjuvant chemotherapy as concept after local treatment of colorectal metastases has not been proven to be successful by phase III trials. Accordingly, a standard of care to improve relapse rates and long-term survival is not established and adjuvant chemotherapy cannot be recommended as a standard therapy due to limited evidence in literature. The PORT trial aims to generate evidence that post-resection/ablation/radiation chemotherapy improves the survival in patients with metastatic colorectal cancer.

Methods

Patients to be included into this trial must have synchronous or metachronous metastases of colorectal cancer—either resected (R0 or R1) and/or effectively treated by ablation or radiation within 3–10 weeks before randomization—and have the primary tumor resected, without radiographic evidence of active metastatic disease at study entry. The primary endpoint of the trial is progression-free survival after 24 months, secondary endpoints include overall survival, safety, quality of life, treatments (including efficacy) beyond study participation, translational endpoints, and others. One arm of the study comprising 2/3 of the population will be treated for 6 months with modified FOLFOXIRI or modified FOLFOX6 (investigator´s choice, depending on the performance status of the patients but determined before randomization), while the other arm (1/3 of the population) will be observed and undergo scheduled follow-up computed tomography scans according to the interventional arm.

Discussion

Optimal oncological management after removal of colorectal metastases is unclear. The PORT trial aims to generate evidence that additive/adjuvant chemotherapy after definitive treatment of colorectal metastases improves progression free and overall survival in patients with colorectal cancer.

Trial registration

This study is registered with clinicaltrials.gov (NCT05008809) and EudraCT (2020–006,144-18).
Treatment of open-angle glaucoma and ocular hypertension with preservative-free tafluprost/timolol fixed-dose combination therapy: 6 case reports and clinical outcomes
Authors: Ansari E. , Chappiti S. , Pavicic-Astalos J. , Pinto-Bonilla J. C. , Riva I. , Sacchi M. , Saénz-Francés F.
Published: April 2022

Background

Treatment of open angle glaucoma (OAG) and/or ocular hypertension (OHT) focuses on achievement of target intraocular pressure (IOP), with the objective of slowing disease progression. However, ocular surface health is an important consideration in the optimization of treatment. We report 6 patient cases in which enhanced IOP control was achieved following appropriate management of ocular surface inflammation and a therapeutic switch to the preservative-free (PF) tafluprost (0.0015%)/timolol (0.5%) fixed-dose combination (FC).

Case presentation

Six patient cases, aged 48–74 years, presented with OAG or OHT. Each patient had signs and symptoms of ocular surface disease (OSD). Cases 1–3 were each receiving maximal medical therapy for OAG; regimens comprising prostaglandin analogue (PGA), β-blocker, carbonic anhydrase inhibitor (CAI) and α-2 agonist agents (including treatments containing preservative agent). Cases 1 and 2 reported IOP values ≥23 mmHg in each eye, and wide IOP fluctuations were identified when reviewing patient data concerning case 3 (11–20 mmHg). Maximal therapy was ceased and PF tafluprost/timolol FC was initiated, after which the signs and symptoms of OSD were improved and IOP was reduced (≤18 mmHg for cases 1–3) and stabilized. Cases 4 and 5 were diagnosed with OAG and case 6 had OHT. Each had symptoms and signs of OSD and were treated with a preserved PGA monotherapy (latanoprost 0.005% or bimatoprost 0.03%). At presentation, IOP was 24 mmHg in both eyes (case 4), ≥18 mmHg (case 5) and ≥ 22 mmHg (case 6). Following a switch to the PF tafluprost/timolol FC, OSD symptoms were improved and IOP was 14 mmHg (both eyes; case 4), ≤14 mmHg (case 5) and 16 mmHg (both eyes; case 6).

Conclusions

In addition to IOP-lowering efficacy, approaches to the management of OAG and OHT should consider the impact of treatment tolerability and the susceptibility of these patients to OSD. The presence of ocular surface inflammation appears to be detrimental to adherence and therefore to the effectiveness of topical medications. Addressing OSD through the use of PF FC formations, such as the PF tafluprost/timolol FC, reduces exposure to potentially toxic agents and facilitates improvements in IOP control.
The ocular biometry characteristics of young patients with primary angle-closure glaucoma
Authors: Xu Yi , Tan Qian , Li Chunyan , Liu Dan
Published: April 2022

Background

Although primary angle-closure glaucoma (PACG) mainly occurs in elderly people, diagnosis of PACG in young patients is not uncommon. So far, there is no article specialized on the ocular anatomical characteristics in these patients.In this study, ocular anatomical characteristics in young PACG patients are analyzed.

Methods

In this retrospective, comparative study, patients diagnosed with PACG and received ultrasound biomicroscopy (UBM) examination in our department were included. Patients were divided into two groups: a young group composed of patients ≤ 45 years and an old group composed of patients > 45 years. A-scan ultrasonography and ultrasound biomicroscopy (UBM) were used to measure ocular biometric parameters of patients in the two groups including axial length (AL), lens thickness (LT), central anterior chamber depth (ACD), anterior chamber width (ACW), angle opening distance 500 (AOD500), anterior chamber angle 500 (ACA500), iris thickness 1000 μm from the iris root (IT1000), iris thickness 500 μm from the iris root (IT500), trabecular-ciliary process angle (TCPA), trabecular-ciliary process distance (TCPD), scleral– ciliary process angle (SCPA), lens vault (LV), and pupil diameter (PD). Plateau iris (PI) and basal iris insertion were determined from UBM images, and the prevalence of PI and basal iris insertion were compared between the two groups. The incidence of postoperative malignant glaucoma (MG) was also determined in both groups and ocular anatomical predictors for the development of MG were evaluated in young PACG patients.

Results

One hundred fifteen patients were included into young group and 480 patients were included into old group. The young group had shorter TCPD, shorter AL, narrower TCPA, narrower SCPA thinner Lens compared to the old group. There were no significant differences in ACD, AOD 500, ACA500, LV, IT500, IT1000, PD or ACW between the two groups. The prevalence of PI was 22.6% in old group and 66.1% in young group (P < 0.001). More young PACG patients displayed basal iris insertion compared to old PACG patients (P < 0.001). 87 patients in the young group and 201 patients in the old group underwent trabeculectomy in our study. Among these patients, 21 young patients and 11 old patients developed MG after trabeculectomy (P < 0.001).

Conclusions

Shorter AL, more anteriorly positioned ciliary body, higher prevalence of PI may be responsible for the etiology of young PACG patients. Our results suggest that shorter AL, shorter TCPD and narrower TCPA may be predictors for development of MG in young PACG patients after trabeculectomy.
Child transmission of SARS-CoV-2: a systematic review and meta-analysis
Authors: Silverberg Sarah L , Zhang Bei Yuan , Li Shu Nan Jessica , Burgert Conrad , Shulha Hennady P , Kitchin Vanessa , Sauvé Laura , Sadarangani Manish
Published: April 2022

Background

Understanding of the role of children in COVID-19 transmission has significant implications for school and childcare policies, as well as appropriate targeting of vaccine campaigns. The objective of this systematic review was to identify the role of children in SARS-CoV-2 transmission to other children and adults.

Methods

MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and Web of Science were electronically searched for articles published before March 31, 2021. Studies of child-to-child and child-to-adult transmission and quantified the incidence of index and resulting secondary attack rates of children and adults in schools, households, and other congregate pediatric settings were identified. All articles describing confirmed transmission of SARS-CoV-2 from a child were included. PRISMA guidelines for data abstraction were followed, with each step conducted by two reviewers.

Results

40 of 6110 articles identified met inclusion criteria. Overall, there were 0.8 secondary cases per primary index case, with a secondary attack rate of 8.4% among known contacts. The secondary attack rate was 26.4% among adult contacts versus 5.7% amongst child contacts. The pooled estimate of a contact of a pediatric index case being infected as secondary case was 0.10 (95% CI 0.03-0.25).

Conclusions

Children transmit COVID-19 at a lower rate to children than to adults. Household adults are at highest risk of transmission from an infected child, more so than adults or children in other settings.