Nevin Manimala

Beijing Da Xue Xue Bao Yi Xue Ban. 2023 Apr 18;55(2):228-233.

ABSTRACT

OBJECTIVE: To investigate the value of using MDM2 amplification probe and DDIT3 dual-color, break-apart rearrangement probe fluorescence in situ hybridization (FISH) technique in the diagnosis of liposarcoma.

METHODS: In the study, 62 cases of liposarcoma diagnosed in Peking University First Hospital from January 2015 to December 2019 were analysed for clinicopathological information. Of these 62 cases of liposarcoma, all were analysed for MDM2 amplification and 48 cases were analysed for DDIT3 rearrangement using a FISH technique. Our study aimed to evaluate the status of MDM2 and DDIT3 by FISH in liposarcoma and correlate it with diagnosis of different subtypes of liposarcoma. The subtypes of liposarcoma were classified according to the FISH results, combined with the relevant clinicopathological features.

RESULTS: The patients aged 31-89 years (mean: 59 years) with a 1.75:1 male to female ratio. Histologically, there were 20 cases of atypical lipomatous tumour/well-differentiated liposarcoma (ALT/WDLPS), 26 cases of dedifferentiated liposarcoma (DDLPS), 13 myxoid liposarcoma (MLPS) and 3 pleomorphic liposarcoma (PLPS). Tumors with DDLPS (23/26) and WDLPS (8/20) were localized retroperitoneally, while both tumours of MLPS and PLPS were localized extra-retroperitoneally, and the difference of sites among the four subtypes of liposarcoma was statistically significant (P < 0.05). Histologically, varied mucoid matrix could be observed in the four subtypes of liposarcoma, and the difference was statistically significant (P < 0.05). MDM2 gene amplification was demonstrated in all cases of ALT/WDLPS and DDLPS (100%, 20/20 and 26/26 respectively); DDIT3 gene rearrangement was noted only in MLPS (100%, 13/13); most cases of DDLPS (96.2%, 25/26) and ALT/WDLPS (83.3%, 5/6, 6 cases selected for detection) demonstrated the picture of amplification of the DDIT3 telomeric tag. According to the instructions of DDIT3 break-apart rearrangement probe, the 5′ telomere probe and 3′ centromere probe spanned but did not cover the DDIT3 gene itself, on the contrary, the 5′ telomere probe covered the CDK4 gene, while the DDIT3 and CDK4 gene were located adjacent to each other on chromosome, therefore, when the amplification signal appeared on the telomeric tag of the DDIT3 rearrangement probe, it indeed indicated the CDK4 gene amplification rather than the DDIT3 gene rearrangement. Then the 10 cases with DDIT3 telomeric tag amplification were selected for CDK4 and DDIT3 gene amplification probe FISH tests, and all the cases showed CDK4 gene amplification (100%, 10/10) and two of the 10 cases demonstrated co-amplification of CDK4 and DDIT3 (20%, 2/10); DDIT3 polysomy detected by DDIT3 gene rearrangement probe was found in 1 case of DDLPS and 2 cases of PLPS (66.7%, 2/3) with morphology of high-grade malignant tumour and poor prognosis.

CONCLUSION: Our results indicate that a diagnosis of different subtype liposarcoma could be confirmed based on the application of MDM2 and DDIT3 FISH, combined with clinicopathological findings. It is also noteworthy that atypical signals should be correctly interpreted to guide correct treatment of liposarcomas.

PMID:37042132

Psychiatr Serv. 2023 Apr 12:appips20220586. doi: 10.1176/appi.ps.20220586. Online ahead of print.

ABSTRACT

OBJECTIVE: Long-acting injectable antipsychotic medications (LAIAPs) are a valuable and underused treatment for patients with chronic mental illnesses such as schizophrenia and bipolar disorder. This study aimed to examine prescription patterns of LAIAPs among outpatient mental health care service providers in the United States.

METHODS: The authors conducted a secondary analysis of the 2020-2021 National Mental Health Services Survey to assess the percentage of outpatient mental health care service providers (N=9,433) that prescribed LAIAPs to patients. Descriptive statistics were calculated to describe the overall frequency of outpatient facilities prescribing LAIAPs and differences in the specific LAIAPs prescribed. The authors also conducted multivariable analyses to identify facility characteristics associated with likelihood of LAIAP prescribing.

RESULTS: Across all outpatient mental health care service providers, 30.6% prescribed LAIAPs. Community mental health centers were most likely to prescribe LAIAPs (62.6%), whereas partial hospitalization and day programs were least likely (32.1%). The most used LAIAP was paliperidone palmitate (77.7%), and the least used was olanzapine pamoate (29.6%). Providers with programs specifically for patients with serious mental illness (59.5%) and providers with a dedicated first-episode psychosis program (58.2%) were more likely to prescribe LAIAPs than were providers without such programming.

CONCLUSIONS: Prescription of LAIAPs is limited at outpatient mental health care service providers in the United States. Expansion of these services and diversification of delivery models are needed to improve LAIAP prescriptions, which are associated with improved patient outcomes across a broad range of measures.

PMID:37042107 | DOI:10.1176/appi.ps.20220586

Innovations (Phila). 2023 Apr 12:15569845231166929. doi: 10.1177/15569845231166929. Online ahead of print.

ABSTRACT

OBJECTIVE: Considerable variation in primary spontaneous pneumothorax (PSP) management exists in the pediatric population. This study aims to compare nationwide outcomes of children with PSP.

METHODS: The Nationwide Readmissions Database (2016 to 2018) was used to identify patients 1 to 18 years old with PSP. Trauma, secondary pneumothoraces, and elective admissions were excluded. Demographics and complications were compared among patients undergoing initial nonoperative management (NOM; observation or percutaneous drainage) or operative resection using standard statistical tests.

RESULTS: A total of 3,890 patients were identified with PSP (median age, 16 [interquartile range 14 to 17] years). Most (78%) underwent NOM, of which 17% failed requiring operative resection. Of the intent-to-treat cohort, 28% failed NOM during index admission or required repeat percutaneous drainage or operative resection on readmission. Patients treated by NOM had higher 30-day and overall readmission rates compared with operative resection (all P < 0.001). Ipsilateral recurrent pneumothorax was higher in those receiving NOM (13% vs 3%, P < 0.001). Patients from the lowest median household income quartile more frequently received NOM compared with the highest income quartile (82% vs 76%) with more readmissions.

CONCLUSIONS: Patients with PSP who underwent initial NOM experienced higher readmission rates than those receiving operative resection. Furthermore, socioeconomic status was associated with the utilization of nonoperative versus operative management.

PMID:37042098 | DOI:10.1177/15569845231166929

J Intensive Care Med. 2023 Apr 11:8850666231168038. doi: 10.1177/08850666231168038. Online ahead of print.

ABSTRACT

The initial hemodynamic goal during septic shock resuscitation is to achieve a mean arterial pressure (MAP) above 65 mm Hg, although this does not assure a normal tissue perfusion. Capillary refill time (CRT), a marker of skin blood flow, has been validated as a marker of the reperfusion process. The aim of the study was to explore the relationship between MAP and CRT in patients in septic shock. Methods: We systematically reviewed studies which reported CRT and MAP in septic shock patients. Authors of eligible studies were asked to provide necessary data for performing a meta-correlation of Spearman’s rank correlation coefficients. Subgroup analyses were performed, including studies of good quality and studies with higher/lower norepinephrine doses. Results: We identified 10 studies, comprising 917 patients. There were 5 studies considered to be of good quality. A meta-correlation showed a statistically significant but poor negative correlation between MAP and CRT (R = -0.158, range -0.221 to -0.093, P < .001, I2 = 0.0%). Subgroup analysis of best-quality studies gave similar results (R = -0.201, range -0.282 to -0.116, P < .001, I2 = 0.0%). In subanalysis concerning norepinephrine doses, no significant correlations were found. Conclusions: In patients with septic shock, there is poor inverse correlation between MAP and CRT. MAP > 65 mm Hg does not guarantee normalization of CRT.Registration code: PROSPERO: CRD42022355996. Registered on 5 September 2022.

PMID:37042043 | DOI:10.1177/08850666231168038

J Genet Couns. 2023 Apr 11. doi: 10.1002/jgc4.1701. Online ahead of print.

ABSTRACT

This retrospective cohort study assessed the accessibility of a genetic counselor on uptake of preimplantation genetic testing for aneuploidy (PGT-A) and carrier screening in a single academic Reproductive Endocrinology and Infertility (REI) clinic. A total of 420 patients were evaluated with 219 patients counseled by a REI physician only and 201 patients after the addition of a genetic counselor (GC) to the REI clinic team. Cycles initiated before hiring of a GC (pre-GC) were assessed from June 2018 to December 2018 and after integration of a GC (post-GC) from March 2019 to August 2019. Additionally, information regarding carrier screening was collected if available in the medical record. Results showed more patients utilized PGT-A post-GC (9.5% vs. 5.5%), although the difference between groups did not reach statistical significance (p = 0.12). Individuals who were screened post-GC or who started screening pre-GC and continued screening post-GC were screened for a larger number of conditions than if they were only screened pre-GC (median pre-GC = 3, post-GC = 27, pre- and post-GC = 274; p < 0.0001). The change in practice from using physician-only counseling to counseling with accessibility to a GC did not change the utilization of PGT-A in a single clinic.

PMID:37042036 | DOI:10.1002/jgc4.1701

Vet World. 2023 Feb;16(2):414-420. doi: 10.14202/vetworld.2023.414-420. Epub 2023 Feb 28.

ABSTRACT

BACKGROUND AND AIM: People who used to rear companion animals are healthier than others who do not. Gastrointestinal (GI) helminths are common in cats and serve as reservoirs for zoonotic diseases. However, the prevalence of GI parasites in cats in Myanmar has never been reported. This study aimed to estimate the prevalence of GI parasites in cats in Myanmar and to identify the potential risk factors associated with GI parasites.

MATERIALS AND METHODS: A total of 230 fecal samples were collected from seven veterinary clinics and two shelters within the Yangon region from January to May 2022. Sampled cats were classified according to age, gender, and the deworming and rearing practices. Fecal samples were analyzed by fecal wet mount, ethyl acetate centrifugal sedimentation, and zinc sulfate centrifugal flotation techniques. Descriptive data were described, and Pearson’s χ² test was used to identify associated risk factors, such as age, gender, and the deworming and rearing practices.

RESULTS: The overall prevalence of GI parasites was 79.56%, and 57.82% of cats were infected with a diagnostic stage of more than one parasite species. Seven GI parasites were detected, including Ancylostoma spp. (55.65%), Toxocara spp. (46.08%), Trichuris spp. (20.86%), Platynosomum spp. (11.73%), Dipylidium caninum (7.39%), Taenia spp. (4.34%), and Cystoisospora spp. (32.17%). Based on statistical analysis, the deworming and rearing practices were significantly associated (p < 0.05) with GI parasitic infections.

CONCLUSION: This study is the first to reveal the prevalence of GI parasites that could assist the need for effective control measures for zoonotic hookworm and roundworm infections in cats. Even with simple microscopic examination, the remarkably high prevalence of GI parasitic infections warrants regular deworming practice. Further molecular studies should also be performed to understand their genetic diversity.

PMID:37041997 | PMC:PMC10082719 | DOI:10.14202/vetworld.2023.414-420

ERJ Open Res. 2023 Apr 11;9(2):00481-2022. doi: 10.1183/23120541.00481-2022. eCollection 2023 Mar.

ABSTRACT

BACKGROUND: Accurate prognosis is important either after acute infection or during long-term follow-up of patients infected by severe acute respiratory syndrome coronavirus 2. This study aims to predict coronavirus disease 2019 (COVID-19) severity based on clinical and biological indicators, and to identify biomarkers for prognostic assessment.

METHODS: We included 261 Vietnamese COVID-19 patients, who were classified into moderate and severe groups. Disease severity prediction based on biomarkers and clinical parameters was performed by applying machine learning and statistical methods using the combination of clinical and biological data.

RESULTS: The random forest model could predict with 97% accuracy the likelihood of COVID-19 patients who subsequently worsened to the severe condition. The most important indicators were interleukin (IL)-6, ferritin and D-dimer. The model could still predict with 92% accuracy after removing IL-6 from the analysis to generalise the applicability of the model to hospitals with limited capacity for IL-6 testing. The five most effective indicators were C-reactive protein (CRP), D-dimer, IL-6, ferritin and dyspnoea. Two different sets of biomarkers (D-dimer, IL-6 and ferritin, and CRP, D-dimer and IL-6) are applicable for the assessment of disease severity and prognosis. The two biomarker sets were further tested through machine learning algorithms and relatively validated on two Danish COVID-19 patient groups (n=32 and n=100). The results indicated that various biomarker sets combined with clinical data can be used for detection of the potential to develop the severe condition.

CONCLUSION: This study provided a simple and reliable model using two different sets of biomarkers to assess disease severity and predict clinical outcomes in COVID-19 patients in Vietnam.

PMID:37041987 | PMC:PMC9885243 | DOI:10.1183/23120541.00481-2022

Stoch Environ Res Risk Assess. 2023;37(4):1593-1613. doi: 10.1007/s00477-022-02348-2. Epub 2022 Dec 30.

ABSTRACT

With advances in modern worlds technology, huge datasets that show dependencies in space as well as in time occur frequently in practice. As an example, several monitoring stations at different geographical locations track hourly concentration measurements of a number of air pollutants for several years. Such a dataset contains thousands of multivariate observations, thus, proper statistical analysis needs to account for dependencies in space and time between and among the different monitored variables. To simplify the consequent multivariate spatio-temporal statistical analysis it might be of interest to detect linear transformations of the original observations that result in straightforward interpretative, spatio-temporally uncorrelated processes that are also highly likely to have a real physical meaning. Blind source separation (BSS) represents a statistical methodology which has the aim to recover so-called latent processes, that exactly meet the former requirements. BSS was already successfully used in sole temporal and sole spatial applications with great success, but, it was not yet introduced for the spatio-temporal case. In this contribution, a reasonable and innovative generalization of BSS for multivariate space-time random fields (stBSS), under second-order stationarity, is proposed, together with two space-time extensions of the well-known algorithms for multiple unknown signals extraction (stAMUSE) and the second-order blind identification (stSOBI) which solve the formulated problem. Furthermore, symmetry and separability properties of the model are elaborated and connections to the space-time linear model of coregionalization and to the classical principal component analysis are drawn. Finally, the usefulness of the new methods is shown in a thorough simulation study and on a real environmental application.

PMID:37041981 | PMC:PMC10081984 | DOI:10.1007/s00477-022-02348-2

Diabetes Obes Metab. 2023 Apr 11. doi: 10.1111/dom.15084. Online ahead of print.

ABSTRACT

AIM: The lack of longitudinal metabolomics data and the statistical techniques to analyze them has limited the understanding of the metabolite levels related to type 2 diabetes (T2D) onset. Thus, we carried out logistic regression analysis and simultaneously proposed new approaches based on residuals of multiple logistic regression and geometric angle-based clustering for the analysis in T2D onset-specific metabolic changes.

METHODS: We used the 6th, 7th, and 8th follow-up data from 2013, 2015, and 2017 among the Korea Association REsource (KARE) cohort data. Semi-targeted metabolite analysis was performed using ultra performance liquid chromatography/triple quadrupole-mass spectrometry (UPLC/TQ-MS) systems.

RESULTS: Since the results from the multiple logistic regression and a single metabolite in a logistic regression analysis varied dramatically, we recommend using models that consider potential multicollinearity among metabolites. The residual-based approach particularly identified neurotransmitters or related precursors as T2D onset-specific metabolites. By using geometric angle-based pattern clustering studies, ketone bodies and carnitines are observed as disease onset specific metabolites and separated from others.

CONCLUSIONS: To treat patients with early-stage insulin resistance and dyslipidemia when metabolic disorders are still reversible, our findings may contribute to a greater understanding of how metabolomics could be used in disease intervention strategies in the early stages of T2D. This article is protected by copyright. All rights reserved.

PMID:37041660 | DOI:10.1111/dom.15084

Patient Saf Surg. 2023 Apr 11;17(1):7. doi: 10.1186/s13037-023-00358-9.

ABSTRACT

BACKGROUND: The early surge of the novel coronavirus disease 2019 (COVID-19) pandemic introduced a significant clinical challenge due to the high case-fatality rate in absence of evidence-based recommendations. The empirical treatment modalities were relegated to historical expertise from the traditional management of acute respiratory distress syndrome (ARDS) in conjunction with off-label pharmaceutical agents endorsed under the “emergency use authorization” (EUA) paradigm by regulatory agencies. This study was designed to evaluate the insights from the “fail-and-learn” strategy in 2020 before the availability of COVID-19 vaccines and access to reliable insights from high-quality randomized controlled trials.

METHODS: A retrospective, multicenter, propensity-matched, case-control study was performed on a data registry comprising 186 hospitals from a national health care system in the United States, designed to investigate the efficacy of empirical treatment modalities during the early surge of the COVID-19 pandemic in 2020. Reflective of the time-windows of the initial two surges of the pandemic in 2020, patients were stratified into “Early 2020” (March 1-June 30) versus “Late 2020” (July 1-December 31) study cohorts. Logistic regression was applied to determine the efficacy of prevalent medications (remdesivir, azithromycin, hydroxychloroquine, corticosteroids, tocilizumab) and supplemental oxygen delivery modalities (invasive vs. non-invasive ventilation) on patient outcomes. The primary outcome measure was in-hospital mortality. Group comparisons were adjusted for covariates related to age, gender, ethnicity, body weight, comorbidities, and treatment modalities pertinent to organ failure replacement.

RESULTS: From a total of 87,788 patients in the multicenter data registry screened in this study, 9,638 patients were included who received 19,763 COVID-19 medications during the first two waves of the 2020 pandemic. The results showed a minimal, yet statistically significant, association with hydroxychloroquine in “Early 2020” and remdesivir in “Late 2020” with reduced odds of mortality (odds ratios 0.72 and 0.76, respectively; P = 0.01). Azithromycin was the only medication associated with decreased odds of mortality during both study time-windows (odds ratios 0.79 and 0.68, respectively; P < 0.01). In contrast, the necessity for oxygen supply showed significantly increased odds of mortality beyond the effect of all investigated medications. Of all the covariates associated with increased mortality, invasive mechanical ventilation had the highest odds ratios of 8.34 in the first surge and 9.46 in in the second surge of the pandemic (P < 0.01).

CONCLUSION: This retrospective multicenter observational cohort study on 9,638 hospitalized patients with severe COVID-19 during revealed that the necessity for invasive ventilation had the highest odds of mortality, beyond the variable effects observed by administration of the prevalent EUA-approved investigational drugs during the first two surges of the early 2020 pandemic in the United States.

PMID:37041643 | DOI:10.1186/s13037-023-00358-9