Nevin Manimala

Open Forum Infect Dis. 2023 Oct 20;10(11):ofad525. doi: 10.1093/ofid/ofad525. eCollection 2023 Nov.

ABSTRACT

BACKGROUND: We evaluated the safety and efficacy of XAV-19, an antispike glyco-humanized swine polyclonal neutralizing antibody in patients hospitalized with severe coronavirus disease 2019 (COVID-19).

METHODS: This phase 2b clinical trial enrolled adult patients from 34 hospitals in France. Eligible patients had a confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 within 14 days of onset of symptoms that required hospitalization for low-flow oxygen therapy (<6 L/min of oxygen). Patients were randomly assigned to receive a single intravenous infusion of 2 mg/kg of XAV-19 or placebo. The primary end point was the occurrence of death or severe respiratory failure between baseline and day 15.

RESULTS: Between January 12, 2021, and April 16, 2021, 398 patients were enrolled in the study and randomly assigned to XAV-19 or placebo. The modified intention-to-treat population comprised 388 participants who received full perfusion of XAV-19 (199 patients) or placebo (189 patients). The mean (SD) age was 59.8 (12.4) years, 249 (64.2%) individuals were men, and the median time (interquartile range) from symptom onset to enrollment was 9 (7-10) days. There was no statistically significant decrease in the cumulative incidence of death or severe respiratory failure through day 15 in the XAV-19 group vs the placebo group (53/199 [26.6%] vs 48/189 [25.4%]; adjusted risk difference, 0.6%; 95% CI, -6% to 7%; hazard ratio, 1.03; 95% CI, 0.64-1.66; P = .90). In the safety population, adverse events were reported in 75.4% of 199 patients in the XAV-19 group and in 76.3% of 190 patients in the placebo group through D29.

CONCLUSIONS: Among patients hospitalized with COVID-19 requiring low-flow oxygen therapy, treatment with a single intravenous dose of XAV-19, compared with placebo, did not show a significant difference in terms of disease progression at day 15.

PMID:37942459 | PMC:PMC10629360 | DOI:10.1093/ofid/ofad525

Strategies Trauma Limb Reconstr. 2023 May-Aug;18(2):100-105. doi: 10.5005/jp-journals-10080-1589.

ABSTRACT

AIM: Non-unions have been traditionally classified as atrophic, oligotrophic and hypertrophic and their management was primarily dictated by that. In our Unit, we have based our treatment rationale mainly on the stability of the metalwork and the presence of symptoms rather than the radiologic appearance of the non-union or the presence of infection. The aim was to present the treatment algorithm for lower limb long bone non-union following operative fixation.

MATERIALS AND METHODS: All patients treated for a femoral or tibial non-union following fixation between 2014 and 2020 in our unit and with a minimum follow-up of 2 years were included. Non-union was defined as having no evidence of fracture healing in any cortices six months after the index procedure. Union was defined as bridging callus in at least three cortices visualized on at least two orthogonal radiographs. Information retrieved included demographic and fracture characteristics, presence of infection, evidence of metalwork stability and treatment. Outcome measures included union rate, time to union and complications. Data were analysed with the Statistical Program for Social Sciences (SPSS) using contingency tables and linear regression. A p-value of less than 0.05 was considered statistically significant.

RESULTS: Seventy-seven consecutive patients were included in the study. Union was achieved in 91% of the cases, while union was noted in all the patients treated non-operatively. The mean time to union was 14.49 months (9.98). Complications were encountered in 20 of the patients and the most common were docking site non-union and metalwork breakage. Infection was the only factor that affected time to union in a statistically significant manner (p = 0.006).

CONCLUSION: The results of our study suggest that in cases of long bone non-union following operative fixation using signs of metalwork instability and the presence of clinical symptoms as the main indication for surgical intervention provides a satisfactory outcome. This approach prevented operative management in a large proportion of patients.

CLINICAL SIGNIFICANCE: This article presents an algorithmic approach that could aid clinicians in their decision-making in long-bone non-union management.

LEVEL OF EVIDENCE: Therapeutic level III.

HOW TO CITE THIS ARTICLE: Poutoglidou F, Krkovic M. The Cambridge Experience with Lower Limb Long Bone Non-union Following Fixation and the Treatment Algorithm. Strategies Trauma Limb Reconstr 2023;18(2):100-105.

PMID:37942431 | PMC:PMC10628614 | DOI:10.5005/jp-journals-10080-1589

Strategies Trauma Limb Reconstr. 2023 May-Aug;18(2):67-72. doi: 10.5005/jp-journals-10080-1591.

ABSTRACT

AIMS: This study aims to report the medium term outcomes of circumferential periosteal release of the distal femur and distal tibia in treating paediatric leg length discrepancy (LLD).

MATERIALS AND METHODS: A retrospective case series was performed on all patients undergoing circumferential periosteal release of the distal femur and/or tibia between 2006 and 2019. Data collected included demographics, surgical indications, post-operative leg lengths, and complications. Leg length discrepancy was calculated as actual values and percentages of the longest limb length. Final actual and percentage discrepancies were compared to initial discrepancies using a paired t-test. Patterns of discrepancy over time were analysed using linear mixed models.

RESULTS: Eighteen patients (11 males) were identified, who underwent 25 procedures. The mean age at first surgery was 5.8 (range, 2-13). The commonest indication was congenital limb deficiency (7 patients). Five patients underwent repeat periosteal release, and one patient had three releases. The mean follow-up was 63 months [standard deviation (SD), 33.9]. Fifteen patients had sufficient data for statistical analysis.The mean actual discrepancy decreased from 2.07 cm (SD, 1.07) to 1.12 cm (SD, 1.62), and the mean relative discrepancy from 4.3% (SD, 2.8) to 1.5% (SD, 2.4). Significant mean reductions were seen in both actual discrepancies [0.61 cm (95% CI: 0.05-1.16; p = 0.034)], and percentage discrepancy [2.10% (95% CI: 1.0-3.1, p = <0.001]). In five patients, the operated limb overgrew the contralateral limb. Patients whose operated limb overgrew still had a reduction in LLD, with a mean residual discrepancy less than 1 cm (mean 0.7 cm, 95% CI: From -0.9 to 2.4).

CONCLUSION: Circumferential periosteal release produces a significant decrease in both actual and percentage LLD. We believe this procedure is best indicated in younger patients with congenital LLD in whom the discrepancy is predicted to increase as they age.

CLINICAL SIGNIFICANCE: Circumferential periosteal release produces a significant decrease in LLD. This procedure can be used to manage symptoms during growth, particularly at the point where orthotic usage may become problematic, and to potentially reduce the magnitude of surgery needed at an older age.

HOW TO CITE THIS ARTICLE: Chatterton BD, Kuiper JH, Williams DP. Circumferential Periosteal Release to Treat Paediatric Leg Length Discrepancy: Medium Term Outcomes. Strategies Trauma Limb Reconstr 2023;18(2):67-72.

PMID:37942428 | PMC:PMC10628615 | DOI:10.5005/jp-journals-10080-1591

J Cardiopulm Rehabil Prev. 2023 Nov 8. doi: 10.1097/HCR.0000000000000836. Online ahead of print.

ABSTRACT

PURPOSE: The 6-min walk test (6MWT) is commonly used to assess functional exercise capacity in people with chronic respiratory disease in both clinical and research settings. However, two tests are required to achieve accurate results, due to a well-documented learning effect for the 6-min walk distance (6MWD). Whether it is possible to reduce or eliminate the learning effect by optimizing 6MWT instructions is not known.

METHODS: People with chronic respiratory disease referred to pulmonary rehabilitation undertook two 6MWT with random allocation to modified instructions (fast-walk as fast as possible; n = 46) or usual instructions (far-walk as far as possible; n = 49). The primary outcome was the learning effect, defined as the difference in the 6MWD between test one and test two. Subgroup analyses investigated whether effects varied in those who were naïve to the 6MWT or according to diagnosis (chronic obstructive pulmonary disease, interstitial lung disease, and bronchiectasis).

RESULTS: A learning effect was present in both groups, with a mean improvement in the 6MWD on the second test of 14 m in the fast (modified) group (95% CI, 6-22) and 11 m in the far (usual) group (95% CI, 4-19). There was no statistically or clinically significant difference between groups in the magnitude of the learning effect (between-group difference -3 m, 95% CI, -14 to 8). There was no significant effect of naivety to the 6MWT or diagnosis.

CONCLUSION: The current recommended procedures for the 6MWT, including standardized instructions and performance of two tests on each occasion, should be retained.

PMID:37941096 | DOI:10.1097/HCR.0000000000000836

Res Involv Engagem. 2023 Nov 8;9(1):102. doi: 10.1186/s40900-023-00513-7.

ABSTRACT

BACKGROUND: Patient and Public Involvement and Engagement (PPIE) is important to all aspects of health research. However, there are few examples of successful PPIE in statistical methodology research. One of the reasons for this relates to challenges in the identification of individuals interested in statistical methodology research projects, and ambiguities over the importance of PPIE to these projects.

METHODS: This project was conducted between August 2022 and August 2023. The aim is to report the process of the development of an accessible animation to describe what statistical methodology is and the importance of PPIE in statistical methodology research projects. For this, we combined storyboarding and scriptwriting with feedback from PPIE members and researchers.

RESULTS: After three stages that incorporated feedback from the relevant stakeholders, we produced a final animation about PPIE in statistical methodology. The resulting animation used minimal text, simple animation techniques and was of short duration (< 3 min) to optimise the communication of the key messages clearly and effectively.

CONCLUSIONS: The resulting animation provides a starting point for members of the public to learn about PPIE in statistical methodology research and for methodologists who wish to conduct PPIE. We recommend further work to explore ways in which members of the public can be more meaningfully involved in methodology research.

PMID:37941086 | DOI:10.1186/s40900-023-00513-7

Eur J Med Res. 2023 Nov 8;28(1):494. doi: 10.1186/s40001-023-01481-0.

ABSTRACT

The treatment of lumbar spinal synovial cysts (LSCs) which are relatively rare but can cause neurogenic dysfunction and intractable pain has been a controversial topic for many years. Surgical excision of LSCs is the standard treatment for patients in whom conservative treatment options fail. This meta-analysis was undertaken to compare clinical outcomes between minimally invasive approaches using tubular retractors (microscopic vs. endoscopic) and traditional percutaneous approaches for LSCs. Studies reporting surgical management of LSCs were searched in the Cochrane Library, PubMed and Web of Science database. This meta-analysis was reported following the PRISMA Statement, registered in Prospero (CRD42021288992). A total of 1833 patients were included from both the related relevant studies (41 studies, n = 1831) and the present series (n = 2). Meta-analysis of minimally invasive tubular approaches revealed no statistically significant difference in pain improvement, dural tear, residual cyst, recurrence and operation time between minimal groups with traditional groups (p > 0.05). Minimal groups had better Functional improvement of 100% (95% CI 1.00-1.00; p < 0.001, I² = 75.3%) and less reoperation rates of 0% (95% CI – 0.00-0.00; p = 0.007, I² = 47.1%). Postoperative length of hospital stay and intraoperative bleeding in minimal groups were also less than traditional groups (p < 0.05). Subgroup analysis revealed endoscopic groups had less operation time (p = 0.004), and there was no significant difference in the rest. For patients with LSCs but without obvious clinical and imaging evidence of vertebral instability, even when preoperative stable grade 1 spondylolisthesis is present, minimally invasive tubular approaches without fusion may provide the best outcome in surgical management.

PMID:37941083 | DOI:10.1186/s40001-023-01481-0

J Health Popul Nutr. 2023 Nov 8;42(1):123. doi: 10.1186/s41043-023-00458-3.

ABSTRACT

BACKGROUND: Uric acid/high-density lipoprotein cholesterol ratio (UHR) is a novel index of inflammation and metabolism that has been investigated in various diseases. However, association between UHR and hypertension among reproductive-aged women is unclear.

METHODS: In this cross-sectional study, we investigated the association between serum UHR and hypertension among 5485 women aged 20-44 years based on the National Health and Nutrition Examination Survey (NHANES) database using various methods, including univariate and multivariate logistic regression analysis, stratified analysis, and spline regression. P < 0.05 was considered statistically significant.

RESULTS: There was significant difference in UHR between the women with and without hypertension (P < 0.001). After adjusting for several covariates, UHR was positively correlated with hypertension (OR > 1, P < 0.001). In the subgroup analysis, the positive correlations still remained between UHR and hypertension in women with various age and those with BMI ≥ 30 kg/m² (P < 0.05) excepted for adjusting for all covariates. We further found an inflection point of the threshold effect for UHR, and the prevalence of hypertension showed different increased trends below and above the threshold.

CONCLUSION: This study indicated a positive association between serum UHR and hypertension among reproductive-aged women, indicating that UHR is a potential clinical marker of hypertension in women.

PMID:37941076 | DOI:10.1186/s41043-023-00458-3

Eur J Med Res. 2023 Nov 9;28(1):504. doi: 10.1186/s40001-023-01470-3.

ABSTRACT

OBJECTIVE: In left breast radiotherapy (RT) desired heart doses may be achieved without heart-sparing RT techniques in some patients. We aimed to examine the existence of predictive factors and cutoff points to determine which patients are the main candidates for heart-sparing RT techniques.

MATERIAL AND METHOD: Dosimetric data for left breast cancer was examined. RT plans were made at conventional doses to the breast and peripheral lymph nodes. Statistical analyses were performed using SPSS 22.0 (SPSS Inc., IBM Corp., Armonk, NY).

RESULT: 114 cases were evaluated by ROC (Receiver operating characteristic) analysis in the breast-conserving surgery (BCS) and mastectomy groups. While only left lung volume (AUC: 0.74, 95% CI 0.61-0.87, p = 0.002) was significant in BCS cases, in cases with mastectomy, left lung volume (AUC: 0.81, 95% CI 0.69-0.94, p = 0.002) and lung/heart volume ratio (AUC: 0.83, 95% CI 0.70-0.96, p = 0.001) had a significant relationship with the relevance of heart doses. The cutoff point of 1.92 was selected for the lung/heart volume ratio for the mastectomized patients. Moreover, the cutoff point 1154 cc and 1208 cc was determined for the left lung volume for the BCS and mastectomized patients, respectively.

CONCLUSION: Various cutoff points in left breast RT can be used to predict whether RT plans will meet QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) heart dose limits. Evaluating only these few cutoff points before planning makes it possible to eliminate 70% of patients with BCS and 40% of patients with mastectomy from respiratory-controlled methods, which require time and effort. Patients with lung volume and lung/heart volume ratio smaller than the cutoff values can be considered primary candidates for heart-sparing techniques.

PMID:37941070 | DOI:10.1186/s40001-023-01470-3

Epigenetics Chromatin. 2023 Nov 9;16(1):44. doi: 10.1186/s13072-023-00521-7.

ABSTRACT

BACKGROUND: In a heterogeneous population of cells, individual cells can behave differently and respond variably to the environment. This cellular diversity can be assessed by measuring DNA methylation patterns. The loci with variable methylation patterns are informative of cellular heterogeneity and may serve as biomarkers of diseases and developmental progression. Cell-to-cell methylation heterogeneity can be evaluated through single-cell methylomes or computational techniques for pooled cells. However, the feasibility and performance of these approaches to precisely estimate methylation heterogeneity require further assessment.

RESULTS: Here, we proposed model-based methods adopted from a mathematical framework originally from biodiversity, to estimate genome-wide DNA methylation heterogeneity. We evaluated the performance of our models and the existing methods with feature comparison, and tested on both synthetic datasets and real data. Overall, our methods have demonstrated advantages over others because of their better correlation with the actual heterogeneity. We also demonstrated that methylation heterogeneity offers an additional layer of biological information distinct from the conventional methylation level. In the case studies, we showed that distinct profiles of methylation heterogeneity in CG and non-CG methylation can predict the regulatory roles between genomic elements in Arabidopsis. This opens up a new direction for plant epigenomics. Finally, we demonstrated that our score might be able to identify loci in human cancer samples as putative biomarkers for early cancer detection.

CONCLUSIONS: We adopted the mathematical framework from biodiversity into three model-based methods for analyzing genome-wide DNA methylation heterogeneity to monitor cellular heterogeneity. Our methods, namely MeH, have been implemented, evaluated with existing methods, and are open to the research community.

PMID:37941029 | DOI:10.1186/s13072-023-00521-7

BMC Res Notes. 2023 Nov 8;16(1):323. doi: 10.1186/s13104-023-06586-7.

ABSTRACT

OBJECTIVE: Determining the serotype of circulating virus strains is important in implementing effective vaccination. In this study, Foot-and-Mouth Disease (FMD) Southern African territory 2 (SAT2) specific primers and TaqMan probe were designed towards rapid SAT2 detection and serotyping. The primers were tested by endpoint reverse transcription (RT) polymerase chain reaction (PCR) and quantitative PCR (RT-qPCR) using the vaccine strain SAT2035. The SAT2 serotype-specific RT-qPCR assay was compared with currently used ELISA and VP1 sequencing using Cohen’s kappa statistics.

RESULTS: The primers yielded amplicons of band size 190 bp during endpoint RT-PCR. When coupled with the probe, the primers reaction efficiency was determined to be 99% with an r² value of 0.994. The results show that the SAT2 assay has comparable performance to VP1 sequencing (k = 1) and a moderate degree of agreement with ELISA (k = 0.571). The data shows that the newly designed assay could be considered for serotyping of SAT2 strains. However, for this assay to be complete there is a need to design effective SAT1 and SAT3 primers and probes that can be multiplexed to target other serotypes that co-circulate within relevant FMD endemic pools. For future implementation of the assay there is also a need to increase the number of field samples towards validation of the assay.

PMID:37941022 | DOI:10.1186/s13104-023-06586-7