Nevin Manimala

J Pediatr Surg. 2021 Sep 17:S0022-3468(21)00599-6. doi: 10.1016/j.jpedsurg.2021.09.006. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the relationship between timing of re-introduction of feeds following surgery for Necrotising Enterocolitis (NEC) and important early outcomes.

METHODS: Secondary analysis of prospectively collected data from paediatric surgical units in UK/Ireland of infants who underwent laparotomy for NEC between 01/03/2013 and 28/02/2014. Multivariable logistic regression analysis was used to compare the relationship of early (≤ 7 days) and later (8-27 days) re-introduction of feeding after surgery on death or need for PN at 28 days, correcting for known cofounders.

RESULTS: 41/143 infants (29%) received early and 102/143 infants (71%) had delayed reintroduction of feeding. Infants in the early feeding group had a higher gestational age at birth, higher proportion of growth restriction, lower inotrope requirement, and weremore likely to have undergone primary anastomosis. Following adjustment there was no statistically significant difference detected in the rate of death or need for PN at 28 days, adjusted OR 0.4 (95% CI 0.2-1.1), noting the limited statistical power of this comparison.

CONCLUSIONS: There is no evidence from this study to support a minimum period of 7 days nil by mouth post laparotomy for infants with NEC. Early feed reintroduction following laparotomy for NEC is safe in appropriate cases.

LEVEL OF EVIDENCE: Level II – Treatment Study Group; Prospective comparative study.

PMID:34579967 | DOI:10.1016/j.jpedsurg.2021.09.006

Br J Anaesth. 2021 Aug 30:S0007-0912(21)00546-8. doi: 10.1016/j.bja.2021.07.033. Online ahead of print.

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, particularly those preventing interaction between the viral spike receptor-binding domain and the host angiotensin-converting enzyme 2 receptor, may prevent viral entry into host cells and disease progression.

METHODS: We performed a systematic review, meta-analysis, trial sequential analysis (TSA), and meta-regression of RCTs to evaluate the benefit of convalescent plasma for COVID-19. The primary outcome was 28-30 day mortality. Secondary outcomes included need for mechanical ventilation and ICU admission. Data sources were PubMed, Embase, MedRxiv, and the Cochrane library on July 2, 2021.

RESULTS: We identified 17 RCTs that recruited 15 587 patients with 8027 (51.5%) allocated to receive convalescent plasma. Convalescent plasma use was not associated with a mortality benefit (24.7% vs 25.5%; odds ratio [OR]=0.94 [0.85-1.04]; P=0.23; I²=4%; TSA adjusted confidence interval [CI], 0.84-1.05), or reduction in need for mechanical ventilation (15.7% vs 15.4%; OR=1.01 [0.92-1.11]; P=0.82; I²=0%; TSA adjusted CI, 0.91-1.13), or ICU admission (22.4% vs 16.7%; OR=0.80 [0.21-3.09]; P=0.75; I²=63%; TSA adjusted CI, 0.0-196.05). Meta-regression did not reveal association with titre of convalescent plasma, timing of administration, or risk of death and treatment effect (P>0.05). Risk of bias was high in most studies.

CONCLUSIONS: In patients with COVID-19, there was no clear mortality benefit associated with convalescent plasma treatment. In patients with mild disease, convalescent plasma did not prevent either the need for mechanical ventilation or ICU admission.

CLINICAL TRIAL REGISTRATION: CRD42021234201 (PROSPERO).

PMID:34579942 | DOI:10.1016/j.bja.2021.07.033

Encephale. 2021 Sep 24:S0013-7006(21)00168-8. doi: 10.1016/j.encep.2021.05.004. Online ahead of print.

ABSTRACT

BACKGROUND: Suicide is a leading yet underestimated cause of death in the world and in France. The goal of our study was to determine the impact at 3 months of a large-scale simulation program on suicide risk assessment for first-year medical residents.

METHODS: All the first-year medical residents participated in the simulation program that included a session on suicide risk assessment. The scenario was carried out by a standardized patient (professional actor) who had a normal check-up at the ER after a chest pain. He verbalized suicidal thoughts to an ER nurse due to a recent divorce and social difficulties, who then reported it to the resident. The latter had to assess suicide risk on his own. The QECS “Questionnaire de connaissances relatives au suicide” was used to assess knowledge of suicide before the training session (T0) and 3 months later (T1). A pre/post comparison was performed with a paired t-test.

RESULTS: 420 residents participated in this study. A total of 273 matching questionnaires was obtained. A statistically significant theoretical knowledge improvement was found at 3 months of the session for all the residents.

LIMITATIONS: The absence of a control group and data loss were some of the major limitations of our study. Another limitation corresponds to the lack of additional questions, such as levels of interest, former and recent training, level of experience, attitudes, and self-competency in suicide risk assessment before and after the simulation program that could have helped to interpret the obtained results and their variation. Moreover, the exact effects of this increased knowledge on clinical practice has not been measured in our study.

CONCLUSION: This is an unprecedented, large-scale attempt in France to allow all the medical residents to practice suicide risk assessment. This simulation-based training had a positive impact at 3 months on the knowledge of suicide in medical residents.

PMID:34579939 | DOI:10.1016/j.encep.2021.05.004

Encephale. 2021 Sep 24:S0013-7006(21)00173-1. doi: 10.1016/j.encep.2021.05.006. Online ahead of print.

ABSTRACT

Philosophy of Mind is currently one of the most prolific fields of research in philosophy and has witnessed a progressive hybridization with cognitive science. It focuses on fundamental questions to neuroscience and psychiatry, such as the nature of mental states and cognitive processes, or the relationships between mental states and the world. Anticipating the accumulation of experimental data from neuroscience, it provides a framework for the generation of theories in cognitive science. Philosophy of mind has thus laid the foundations of the conceptual space within which cognitive sciences have spread: a large part of contemporary theories in cognitive science result from a hybridization of conceptions forged by philosophers of mind and data produced by neuroscientists. Yet contemporary psychiatry is still reluctant to feed on the philosophy of mind, other than through the fragments that emerge from neuroscience. In this paper, we describe the evolution of contemporary philosophy of mind, and we detail its contributions around three central themes for psychiatry: naturalization of mind, mental causality, and subjectivity of mental states. We show how philosophy of mind provide the conceptual framework to link different levels of explanation in psychiatry: from biological to functional, from neurophysiology to cognition, from matter to mind.

PMID:34579938 | DOI:10.1016/j.encep.2021.05.006

Clin Radiol. 2021 Sep 24:S0009-9260(21)00429-3. doi: 10.1016/j.crad.2021.09.004. Online ahead of print.

ABSTRACT

AIM: To determine whether quantitative parameters derived from conventional diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) correlate with the Ki67 proliferation status in musculoskeletal tumours.

MATERIALS AND METHODS: Twenty-eight patients with musculoskeletal tumours diagnosed via surgical specimen histological analysis who underwent standard DWI, IVIM, and DCE were reviewed retrospectively. The mean standard DWI (apparent diffusion coefficient [ADC]), IVIM (pure diffusion coefficient [D], pseudo-diffusion coefficient [D∗] and perfusion fraction [ƒ]), and DCE (volume transfer constant [K^trans], rate constant [K_ep], and extravascular extracellular volume fraction [V_e]) parameters were measured and correlated with the Ki67 index. The Ki67 value was categorised as high (>20%) or low (≤20%).

RESULTS: The ADC and D values correlated negatively with the Ki67 index (r=-0.711∼-0.699, p<0.001), whereas the K^trans and K_ep values correlated positively with the Ki67 index (r=0.389-0.434, p=0.021, 0.041). The ADC and D values were lower (p<0.001), whereas the K^trans and K_ep values were higher (p=0.011, 0.005) in musculoskeletal tumours with a high Ki67 status than in those in a low status. The ADC and D demonstrated the largest area under the receiver-operating characteristic curve (AUC = 0.953), which is statistically bigger than the AUC of K^trans and K_ep (0.784 and 0.802, respectively).

CONCLUSION: ADC, D, K^trans, and K_ep correlate with the Ki67 index. ADC and D are the strongest quantitative parameters for predicting Ki67 status.

PMID:34579866 | DOI:10.1016/j.crad.2021.09.004

J Obstet Gynaecol Res. 2021 Sep 27. doi: 10.1111/jog.15040. Online ahead of print.

ABSTRACT

AIM: The aim of this study was to compare the surgical outcomes between patients who were staged laparoscopically for early-stage endometrioid-type endometrial cancer (EC) between those who underwent prophylactic ligation of uterine arteries (UAs) prior to pelvic lymphadenectomy and the patients who were operated with standard procedure.

METHODS: This retrospective study was conducted in women diagnosed with early-stage and low/intermediate-risk endometrioid-type EC. The control group included patients who underwent standard laparoscopic pelvic lymphadenectomy and the study group concerned patients who underwent prophylactic ligation of UA prior to pelvic lymphadenectomy. The prophylactic ligation of UA procedure was performed at a point just proximal to its origin.

RESULTS: The mean lymph node count dissected in the study group was higher in terms of statistical significance (17.5 ± 2.2 vs. 19.8 ± 3.6, p = 0.003 and p ˂ 0.05). The rate of the patients who had a positive pelvic lymph node detected did not differ between groups (7.4% vs. 16.7%, p = 0.258 and p ˂ 0.05). The operation time (OT) of the patients in the study group did not differ between groups (p = 0.546 and p ˂ 0.05). Hemoglobin drop (-0.5 ± 0.7) and hematocrite drop (-0.8 ± 0.9) values in the study group were found to be lower in the study group (p = 0.000, p = 0.000, and p ˂ 0.05).

CONCLUSIONS: Performing prophylactic ligation of UA at its origin prevents unwanted bleeding and facilitates the laparoscopic pelvic lymphadenectomy procedure.

PMID:34571568 | DOI:10.1111/jog.15040

Klin Monbl Augenheilkd. 2021 Sep 27. doi: 10.1055/a-1525-2588. Online ahead of print.

ABSTRACT

BACKGROUND: The role of CD133 und ABCB5 is discussed in treatment resistance in several types of cancer. The objective of this study was to evaluate whether CD133⁺/ABCB5⁺ colocalization differs in untreated, in beam radiation treated, and in chemotherapy treated retinoblastoma specimens. Additionally, CD133, ABCB5, sphingosine kinase 1, and sphingosine kinase 2 gene expression was analyzed in WERI-RB1 (WERI RB1) and etoposide-resistant WERI RB1 subclones (WERI ETOR).

METHODS: Active human untreated retinoblastoma specimens (n = 12), active human retinoblastoma specimens pretreated with beam radiation before enucleation (n = 8), and active human retinoblastoma specimens pretreated with chemotherapy before enucleation (n = 7) were investigated for localization and expression of CD133 and ABCB5 by immunohistochemistry. Only specimens with IIRC D, but not E, were included in this study. Furthermore, WERI RB1 and WERI ETOR cell lines were analyzed for CD133, ABCB5, sphingosine kinase 1, and sphingosine kinase 2 by the real-time polymerase chain reaction (RT-PCR).

RESULTS: Immunohistochemical analysis revealed the same amount of CD133⁺/ABCB5⁺ colocalization islets in untreated and treated human retinoblastoma specimens. Quantitative RT-PCR analysis showed a statistically significant upregulation of CD133 in WERI ETOR (p = 0.002). No ABCB5 expression was detected in WERI RB1 and WERI ETOR. On the other hand, SPHK1 (p = 0.0027) and SPHK2 (p = 0.017) showed significant downregulation in WERI ETOR compared to WERI RB1.

CONCLUSIONS: CD133⁺/ABCB5⁺ co-localization islets were noted in untreated and treated human retinoblastoma specimens. Therefore, we assume that CD133⁺/ABCB5⁺ islets might play a role in retinoblastoma genesis, but not in retinoblastoma treatment resistance.

PMID:34571550 | DOI:10.1055/a-1525-2588

Handchir Mikrochir Plast Chir. 2021 Sep 27. doi: 10.1055/a-1380-3922. Online ahead of print.

ABSTRACT

BACKGROUND: Microsurgery is a specific surgical expertise that involves operating on very small structures, and requires the assistance of a magnifying device: a microscope or loupes. Several factors have been identified that could affect the quality of microsurgical performance in training or surgical procedures.

OBJECTIVE: The objective of this study was to assess the impact of the selected factors – caffeine, alcohol and physical exercise – on a microsurgical task prior its performance.

METHODS: Ten students from the 5th and 6th years of medical studies who had completed the advanced microsurgical course performed a “6-stitches test” on a latex glove spanned over a cup prior to and after consumption of caffeine, alcohol and performing physical exercises. The times taken to complete the task at baseline and post-exposure were recorded.

RESULTS: The results of the study show a statistically significant positive effect of caffeine and a statistically significant negative effect of physical exercise on microsurgical performance when performed shortly before the task. Small dose of alcohol taken before the task showed had little effect on performance.

PMID:34571547 | DOI:10.1055/a-1380-3922

J Am Med Inform Assoc. 2021 Sep 27:ocab203. doi: 10.1093/jamia/ocab203. Online ahead of print.

ABSTRACT

OBJECTIVE: Deep significance clustering (DICE) is a self-supervised learning framework. DICE identifies clinically similar and risk-stratified subgroups that neither unsupervised clustering algorithms nor supervised risk prediction algorithms alone are guaranteed to generate.

MATERIALS AND METHODS: Enabled by an optimization process that enforces statistical significance between the outcome and subgroup membership, DICE jointly trains 3 components, representation learning, clustering, and outcome prediction while providing interpretability to the deep representations. DICE also allows unseen patients to be predicted into trained subgroups for population-level risk stratification. We evaluated DICE using electronic health record datasets derived from 2 urban hospitals. Outcomes and patient cohorts used include discharge disposition to home among heart failure (HF) patients and acute kidney injury among COVID-19 (Cov-AKI) patients, respectively.

RESULTS: Compared to baseline approaches including principal component analysis, DICE demonstrated superior performance in the cluster purity metrics: Silhouette score (0.48 for HF, 0.51 for Cov-AKI), Calinski-Harabasz index (212 for HF, 254 for Cov-AKI), and Davies-Bouldin index (0.86 for HF, 0.66 for Cov-AKI), and prediction metric: area under the Receiver operating characteristic (ROC) curve (0.83 for HF, 0.78 for Cov-AKI). Clinical evaluation of DICE-generated subgroups revealed more meaningful distributions of member characteristics across subgroups, and higher risk ratios between subgroups. Furthermore, DICE-generated subgroup membership alone was moderately predictive of outcomes.

DISCUSSION: DICE addresses a gap in current machine learning approaches where predicted risk may not lead directly to actionable clinical steps.

CONCLUSION: DICE demonstrated the potential to apply in heterogeneous populations, where having the same quantitative risk does not equate with having a similar clinical profile.

PMID:34571540 | DOI:10.1093/jamia/ocab203

Brief Bioinform. 2021 Sep 24:bbab389. doi: 10.1093/bib/bbab389. Online ahead of print.

ABSTRACT

Pleiotropy has important implication on genetic connection among complex phenotypes and facilitates our understanding of disease etiology. Genome-wide association studies provide an unprecedented opportunity to detect pleiotropic associations; however, efficient pleiotropy test methods are still lacking. We here consider pleiotropy identification from a methodological perspective of high-dimensional composite null hypothesis and propose a powerful gene-based method called MAIUP. MAIUP is constructed based on the traditional intersection-union test with two sets of independent P-values as input and follows a novel idea that was originally proposed under the high-dimensional mediation analysis framework. The key improvement of MAIUP is that it takes the composite null nature of pleiotropy test into account by fitting a three-component mixture null distribution, which can ultimately generate well-calibrated P-values for effective control of family-wise error rate and false discover rate. Another attractive advantage of MAIUP is its ability to effectively address the issue of overlapping subjects commonly encountered in association studies. Simulation studies demonstrate that compared with other methods, only MAIUP can maintain correct type I error control and has higher power across a wide range of scenarios. We apply MAIUP to detect shared associated genes among 14 psychiatric disorders with summary statistics and discover many new pleiotropic genes that are otherwise not identified if failing to account for the issue of composite null hypothesis testing. Functional and enrichment analyses offer additional evidence supporting the validity of these identified pleiotropic genes associated with psychiatric disorders. Overall, MAIUP represents an efficient method for pleiotropy identification.

PMID:34571531 | DOI:10.1093/bib/bbab389