Nevin Manimala

Arch Orthop Trauma Surg. 2021 Oct 3. doi: 10.1007/s00402-021-04195-2. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of this prospective randomised study was to evaluate clinical results and rotational stability at least 2 years after single-bundle anatomic anterior cruciate ligament reconstruction using a quadriceps tendon graft with bone block (BT) and bone-patellar tendon-bone graft (BTB).

MATERIALS AND METHODS: In both groups (BT and BTB), 40 patients selected prospectively at random were evaluated. The mean follow-up after the surgery was 28 months (range 24-33 months). A navigation system was used to measure rotational stability of the knee joint. Cincinnati, Lysholm, and IKDC scores and visual analog score (VAS) were used to evaluate clinical results and the non-parametric Wilcoxon test was used for the statistical analysis.

RESULTS: After the BT reconstruction, the mean internal rotation of the tibia (IR) was 9.5°. In the contralateral healthy knee joint, IR was 8.6° at average. After the BTB reconstruction, the mean IR was 9.9°. In the contralateral healthy knee joint, IR was 8.7° at average. We did not find any statistically significant difference in IR stability between BT and BTB reconstruction. In terms of clinical results, regarding the VAS, patients perceive significantly more pain after the BTB reconstruction (p < 0.05). Kneeling was reported more difficult and painful after BTB reconstruction.

CONCLUSIONS: The BT reconstruction of the ACL provides similar clinical results, less pain, better flexion and the same rotational stability of the knee in comparison with the BTB reconstruction.

PMID:34601649 | DOI:10.1007/s00402-021-04195-2

Brain Imaging Behav. 2021 Oct 2. doi: 10.1007/s11682-021-00552-2. Online ahead of print.

ABSTRACT

Despite the high risk for suicide, relatively few studies have explored the relationship between suicide and brain imaging measures in bipolar disorder. In addition, fewer studies have explored the possibility that altered brain metabolism may be associated with suicide attempt. To begin to fill in these gaps, we evaluated functional (task based fMRI) and metabolic (quantitative T1ρ) differences associated with suicide attempt in participants with bipolar disorder. Thirty-nine participants with bipolar disorder underwent fMRI during a flashing checkerboard task and 27 also underwent quantitative T1ρ. The relationship between neuroimaging and history of suicide attempt was tested using multiple regression while adjusting for age, sex, and current mood state. Differences between two measures of suicide attempt (binary: yes/no and continuous: number of attempts) were quantified using the corrected Akaike Information Criterion. Participants who had attempted suicide had greater fMRI task-related activation in visual areas and the cerebellum. The number of suicide attempts was associated with a difference in BOLD response in the amygdala, prefrontal cortex, and cerebellum. Increased quantitative T1ρ was associated with number of suicide attempts in limbic, basal ganglia, and prefrontal cortex regions. This study is a secondary analysis with a modest sample size. Differences between measures of suicide history may be due to differences in statistical power. History of suicide was associated with limbic, prefrontal, and cerebellar alterations. Results comparing those with and without suicide attempts differed from results using number of suicide attempts, suggesting that these variables have different neurobiological underpinnings.

PMID:34601647 | DOI:10.1007/s11682-021-00552-2

Metabolomics. 2021 Oct 3;17(10):95. doi: 10.1007/s11306-021-01846-8.

ABSTRACT

BACKGROUND: Children and young adults with single ventricle (SV) heart disease frequently develop heart failure (HF) that is intractable and difficult to treat. Our understanding of the molecular and biochemical reasons underlying this is imperfect. Thus, there is an urgent need for biomarkers that predict outcome and provide a rational basis for treatment, and advance our understanding of the basis of HF.

OBJECTIVE: We sought to determine if a metabolomic approach would provide biochemical signatures of HF in SV children and young adults. If significant, these analytes might serve as biomarkers to predict outcome and inform on the biological mechanism(s) of HF.

METHODS: We applied a multi-platform metabolomics approach composed of mass spectrometry (MS) and nuclear magnetic resonance (NMR) which yielded 495 and 26 metabolite measurements respectively. The plasma samples came from a cross-sectional set of young SV subjects, ages 2-19 years with ten control (Con) subjects and 16 SV subjects. Of the SV subjects, nine were diagnosed as congestive HF (SVHF), and 7 were not in HF. Metabolomic data were correlated with clinical status to determine if there was a signature associated with HF.

RESULTS: There were no differences in age, height, weight or sex between the 3 cohorts. However, statistical analysis of the metabolomic profiles using ANOVA revealed 44 metabolites with significant differences between cohorts including 41 profiled by MS and 3 by NMR. These metabolites included acylcarnitines, amino acids, and bile acids, which distinguished Con from all SV subjects. Furthermore, metabolite profiles could distinguish between SV and SVHF subjects.

CONCLUSION: These are the first data to demonstrate a clear metabolomic signature associated with HF in children and young adults with SV. Larger studies are warranted to determine if these findings are predictive of progression to HF in time to provide intervention.

PMID:34601638 | DOI:10.1007/s11306-021-01846-8

Hum Reprod. 2021 Oct 3:deab198. doi: 10.1093/humrep/deab198. Online ahead of print.

ABSTRACT

STUDY QUESTION: What were the utilization, effectiveness and safety of practices in assisted reproductive technologies (ART) globally in 2014 and what global trends could be observed?

SUMMARY ANSWER: The estimated total number of ART cycles conducted in 76 participating countries in 2014 was 1.93 million representing ∼66% of global activity, with 5-year trends including an increase in success rates and proportion of frozen embryo transfer (FET) cycles, improvement in cumulative live birth rates per aspiration, a continued increase in single embryo transfer (SET) and thus a reduction in multiple birth rates, an increase in preimplantation genetic testing and stabilization in the use of intracytoplasmic sperm injection (ICSI).

WHAT IS KNOWN ALREADY: ART is widely practiced throughout the world but continues to be characterized by significant disparities in utilization, practice, effectiveness and safety. The International Committee for Monitoring Assisted Reproductive Technologies (ICMART) annual world report series provides an important instrument for tracking trends in ART treatment and for providing clinical and public health data to ART professionals, health authorities, patients and the general public.

STUDY DESIGN, SIZE, DURATION: A retrospective, cross-sectional survey on ART procedures performed globally during 2014 was carried out. A new method for calculating ART utilization rates and number of babies born was introduced in this latest ICMART world report.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 76 countries and 2 746 ART centres submitted data through national and regional ART registries on ART cycles performed during 2014 and their treatment and pregnancy outcomes. ART cycles and outcomes are described at a country level, regionally and globally. Aggregate country data are processed and analyzed based on methods developed by ICMART.

MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1 629 179 ART cycles were reported for the treatment year 2014. After imputing data for missing values and non-reporting centres in reporting countries, an estimated 1 929 905 cycles resulted in >439 039 babies in reporting countries. From 2010 to 2014, the number of reported non-donor aspirations and FET cycles increased by 37.3% and 67.5%, respectively. The proportion of women aged ≥40 years undergoing non-donor ART increased from 23.2% in 2010 to 27.0% in 2014. ICSI, as a percentage of non-donor aspiration cycles, remained relatively stable at 64.8%. The IVF/ICSI combined delivery rates per fresh aspiration and FET cycle were 19.9% and 24.3%, respectively. In fresh non-donor cycles, SET increased from 30.0% in 2010 to 40.0% in 2014, while the average number of transferred embryos decreased from 1.95 to 1.73-but with wide country variation. The rate of twin deliveries following fresh non-donor transfers continued to decrease, from 20.4% in 2010 to 16.2% in 2014, and the triplet rate decreased from 1.1% to 0.5%. In FET non-donor cycles in 2014, the SET rate was 61.6%, with an average of 1.43 embryos transferred, resulting in twin and triplet rates of 10.1% and 0.2%, respectively. The cumulative delivery rate per aspiration increased from 27.1% in 2010 to 32.1% in 2014. The overall perinatal mortality rate per 1 000 births was 19.4 following fresh IVF/ICSI cycles and 9.5 following FET cycles. Among reporting countries, oocyte donation cycles represented 7.3% of all embryo transfers (89 751 transfer cycles) and resulted in 39 278 babies.

LIMITATIONS, REASONS FOR CAUTION: The data presented are dependent on the quality and completeness of data submitted by individual countries to ICMART directly or through regional registries. This report covers approximately two-thirds of world ART activity. China is a major contributor of global cycles missing from this report. Continued efforts to improve the quality and consistency of ART data reported by registries are still needed, including the use of internationally agreed standard definitions (The International Glossary of Infertility and Fertility Care). A new method was introduced in this report to calculate ART utilization and number of babies born following ART; therefore, these results are not directly comparable with previous reports.

WIDER IMPLICATIONS OF THE FINDINGS: The ICMART world reports provide the most comprehensive global statistical census and review of ART utilization, effectiveness, safety and quality. While ART treatment effectiveness and safety continue to increase globally, the wide disparities in access to treatment, procedures performed and embryo transfer practices warrant attention by clinicians and policymakers. The new method for estimating ART utilization and number of babies born provided more conservative estimates compared to the previuos method.

STUDY FUNDING/COMPETING INTEREST(S): ICMART receives unrestricted grants from Abbott and Ferring Pharmaceuticals. ICMART also acknowledges financial support from the following organizations: American Society for Reproductive Medicine; Asia Pacific Initiative on Reproduction; European Society of Human Reproduction and Embryology; Fertility Society of Australia and New Zealand; Japan Society for Reproductive Medicine; Japan Society of Fertilization and Implantation; Red Latinoamericana de Reproducción Asistida; and the Society for Assisted Reproductive Technology. S.D. reports industry sponsorship for attendance of conference from Ferring, and research grants to support African Network and Registry of ART from Ferring and Merck outside the submitted work. F.Z.-H. reports lectures at organized webinars for Ferring and Merck. O.I. reports honoraria for consulting from Ferring, Merck and ObsEva, as well as honoraria for lectures from Ferring and Merck. G.M.C., J.d.M., M.B., M.S.K. and G.D.A. have nothing to disclose.

TRIAL REGISTRATION NUMBER: N/A.

PMID:34601605 | DOI:10.1093/humrep/deab198

J Nutr. 2021 Oct 2:nxab348. doi: 10.1093/jn/nxab348. Online ahead of print.

ABSTRACT

BACKGROUND: Observational studies have suggested that better protein nutritional status may contribute to prevention of frailty.

OBJECTIVE: To examine this hypothesis using a Mendelian randomization (MR) analysis.

METHODS: We conducted a two-sample MR study using GWAS summary statistics data of the UK Biobank. We applied genetically predicted serum albumin as a primary exposure measure and serum total protein as a secondary exposure measure. The outcome measure was the Rockwood frailty index (FI) based on 49 deficits from 356,432 individuals (53.3% of them were women, with a mean [SD] age of 56.7 [8.0] years. The association between serum protein measures and FI was mainly analyzed by the inverse variance weighted method.

RESULTS: A genetically predicted serum albumin level was not statistically significantly associated with FI in the full sample. However, in women, we observed a preventive association between genetically predicted serum albumin and FI (beta = -0.172 per g/L; 95% confidence interval = -0.336 to -0.007; P = 0.041). In the full sample, genetically predicted serum total protein was inversely associated with FI (beta = -0.153 per g/L; 95% confidence interval = -0.251 to -0.056; P = 0.002). In both women and men, higher serum total protein was significantly inversely associated with FI; regression coefficients were -0.148 per g/L (95% confidence interval = -0.287 to -0.009; P = 0.037) for women, -0.154 per g/L (95% confidence interval = -0.290 to -0.018; P = 0.027) for men.

CONCLUSIONS: The present MR study implies that better protein nutritional status modestly contributes to reducing the risk of frailty.

PMID:34601600 | DOI:10.1093/jn/nxab348

J Clin Endocrinol Metab. 2021 Oct 3:dgab713. doi: 10.1210/clinem/dgab713. Online ahead of print.

ABSTRACT

CONTEXT: The causal role of endogenous estradiol in cancers other than breast and endometrial cancer remains unclear.

OBJECTIVE: To assess the causal associations of endogenous 17β-estradiol (E2), the most potent estrogen, with cancer risk in women through Mendelian randomization.

METHODS: As primary genetic instrument, we used a genetic variant in the CYP19A1 gene that is strongly associated with serum E2 levels. Summary statistics genetic data for the association of the E2 variant with breast, endometrial, and ovarian cancer were obtained from large-scale consortia. We additionally estimated the associations of the E2 variant with any and 20 site-specific cancers in 198 825 women of European descent in UK Biobank. Odds ratios (OR) of cancer per 0.01 unit increase in log-transformed serum E2 levels in pmol/L were estimated using the Wald ratio.

RESULTS: Genetic predisposition to higher serum E2 levels was associated with increased risk of estrogen receptor positive breast cancer (OR 1.02; 95% confidence interval [CI] 1.01-1.03; P=2.5×10 -3), endometrial cancer overall (OR 1.09; 95% CI 1.06-1.11; P=7.3×10 -13), and endometrial cancer of the endometrioid histology subtype (OR 1.10; 95% CI 1.07-1.13; P=2.1×10 -11). There were suggestive associations with breast cancer overall (OR 1.01; 95% CI 1.00-1.02; P=0.02), ovarian cancer of the endometrioid subtype (OR 1.05; 95% CI 1.01-1.10; P=0.02), and stomach cancer (OR 1.12; 95% CI 1.00-1.26; P=0.05), but no significant association with other cancers.

CONCLUSION: This study supports a role of E2 in the development of estrogen receptor positive breast cancer and endometrioid endometrial cancer, but found no strong association with other cancers in women.

PMID:34601599 | DOI:10.1210/clinem/dgab713

Bioinformatics. 2021 Oct 2:btab690. doi: 10.1093/bioinformatics/btab690. Online ahead of print.

ABSTRACT

MOTIVATION: Tea is a cross pollinated woody perennial plant, which is why, application of conventional breeding is limited for its genetic improvement. However, lack of the genome-wide high-density SNP markers and genome-wide haplotype information has greatly hampered the utilization of tea genetic resources towards fast-track tea breeding programs. To address this challenge, we have generated a first-generation haplotype map of tea (Tea HapMap-1). Out-crossing and highly heterozygous nature of tea plants, make them more complicated for DNA level variant discovery.

RESULTS: In the present study, whole genome re-sequencing data of 369 tea genotypes were used to generate 2,334,564 biallelic SNPs and 1,447,985 InDels. Around 2928.04 million paired-end reads were generated with an average mapping depth of ∼0.31X per accession. Identified polymorphic sites in this study will be useful in mapping the genomic regions responsible for important traits of tea. These resources lay the foundation for future research to understand the genetic diversity within tea germplasm and utilize genes that determine tea quality. This will further facilitate the understanding of tea genome evolution and tea metabolite pathways thus, offers an effective germplasm utilization for breeding the tea varieties.

PMID:34601584 | DOI:10.1093/bioinformatics/btab690

Theriogenology. 2021 Sep 25;176:94-103. doi: 10.1016/j.theriogenology.2021.09.025. Online ahead of print.

ABSTRACT

Antifreeze proteins (AFPs) are synthesized by diverse non-mammalian species, allowing them to survive in severely cold environments. Since the 1990s, the scientific literature reports their use for low-temperature preservation of germplasm. The aim of this systematic review was to compile available scientific evidence regarding the use of AFP for low-temperature preservation of several reproductive specimens. Internet databases were consulted using the terms: “antifreeze protein” OR “AFP” OR “antifreeze glycoprotein” OR “AFGP” OR “ice-binding protein” OR “IBP” OR “thermal hysteresis protein” AND “cryopreservation”. From 56 articles, 87 experiments testing AFPs in low-temperature preservation of gametes, embryos or reproductive tissues/cells were fully analyzed and outcomes were annotated. A positive outcome was considered as a statistically significant improvement on any parameter evaluated after low-temperature preservation with AFP, whereas a negative outcome included worsening of any evaluated parameter, in comparison to untreated groups or groups treated with a lower concentration of AFP. The findings indicated that research on the use of AFP as a cryoprotectant for reproductive specimens has increased markedly over the past decade. Some experiments reported both positive and negative results, which depended, on AFP concentration in the preservation media. Variation in the outcomes associated with species was also observed. Among the 66 experiments conducted in mammals, 77.3% resulted in positive, and 28.8% in negative outcomes after the use of AFP. In fishes, positive and negative outcomes were observed in 71.4% and 33.3% of 21 experiments, respectively. Most positive outcomes included preserving cell post-warming survival. The beneficial effect of AFP supports its use in cryobiological approaches used in human and veterinary medicines and animal protein industry. Moreover, combination of different AFP types, or AFP with antioxidants, or even the use of AFP-biosimilar, comprise some promising approaches to be further explored in cryopreservation.

PMID:34600433 | DOI:10.1016/j.theriogenology.2021.09.025

Am J Otolaryngol. 2021 Sep 8;43(1):103200. doi: 10.1016/j.amjoto.2021.103200. Online ahead of print.

ABSTRACT

PURPOSE: Managing hearing health in older adults has become a public health imperative, and cochlear implantation is now the standard of care for aural rehabilitation when hearing aids no longer provide sufficient benefit. The aim of our study was to compare speech performance in cochlear implant patients ≥80 years of age (Very Elderly) to a younger elderly cohort between ages 65-79 years (Less Elderly).

MATERIALS AND METHODS: Data were collected from 53 patients ≥80 years of age and 92 patients age 65-79 years who underwent cochlear implantation by the senior author between April 1, 2017 and May 12, 2020. The primary outcome measure compared preoperative AzBio Quiet scores to 6-month post-activation AzBio Quiet results for both cohorts.

RESULTS: Very Elderly patients progressed from an average AzBio Quiet score of 22% preoperatively to a score of 45% in the implanted ear at 6-months post-activation (p < 0.001) while the Less Elderly progressed from an average score of 27% preoperatively to 60% at 6-months (p < 0.001). Improvements in speech intelligibility were statistically significant within each of these cohorts (p < 0.001). Comparative statistics using independent samples t-test and evaluation of effect size using the Hedges’ g statistic demonstrated a significant difference for average improvement of AzBio in quiet scores between groups with a medium effect size (p = 0.03, g = 0.35). However, when the very oldest patients (90+ years) were removed, the statistical difference between groups disappeared (p = 0.09).

CONCLUSIONS: When assessing CI performance, those over age 65 are typically compared to younger patients; however, this manuscript further stratifies audiometric outcomes for older CI recipients in a single-surgeon, high-volume practice. Our data indicates that for speech intelligibility, patients between age 65-79 perform similarly to CI recipients 80-90 years of age and should not be dismissed as potential cochlear implant candidates.

PMID:34600410 | DOI:10.1016/j.amjoto.2021.103200

Lung Cancer. 2021 Sep 20;161:163-170. doi: 10.1016/j.lungcan.2021.09.011. Online ahead of print.

ABSTRACT

OBJECTIVES: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker of response to immunotherapies targeting programmed death-1/PD-L1 in advanced-stage lung adenocarcinoma. The aim of this study was to investigate the associations between PD-L1 expression and clinicopathological features, prognosis, and driver oncogene alterations in patients with lung adenocarcinoma.

MATERIALS AND METHODS: We evaluated PD-L1 expression in 1,005 surgically resected lung adenocarcinoma specimens, by immunohistochemistry using the 22C3 antibody. PD-L1 positivity was defined based on the proportion of stained tumor cells (TPS) on tissue microarrays: <1% (negative), 1-49% (weakly positive), and ≥ 50% (strongly positive). Correlations between PD-L1 expression and clinicopathological features, prognosis, and driver oncogene (EGFR, KRAS, ALK, ROS1, and RET) alterations in lung adenocarcinoma were analyzed.

RESULTS: PD-L1 expression was negative in 726 (72%) of 1,005 tumors, weakly positive in 161 (16%), and strongly positive in 118 (12%). Male sex, smoking, elevated serum carcinoembryonic antigen levels, advanced pathological stages, high-grade tumors, predominantly solid tumors, tumors with lymphatic permeation or vascular or pleural invasion, tumors without EGFR mutations, and tumors with KRAS mutations were more common in patients with PD-L1-positive tumors (TPS ≥ 1%) than in those with PD-L1-negative tumors (TPS < 1%). PD-L1 positivity was not associated with ALK, ROS1, or RET fusion status. Although PD-L1 positivity was associated with poor overall survival and poor relapse-free survival in all patients, this was not statistically significant after adjusting for prognostic factors in the multivariate analysis. In the subgroup analysis according to driver oncogene alterations, PD-L1 positivity was associated with poor relapse-free survival only in patients with EGFR-mutated tumors.

CONCLUSION: Surgically resected lung adenocarcinomas with increased PD-L1 expression were biologically aggressive tumors that frequently occurred in male smokers. PD-L1 expression and its prognostic significance differed according to driver oncogene alterations.

PMID:34600407 | DOI:10.1016/j.lungcan.2021.09.011