Nevin Manimala

JAMA Oncol. 2023 Apr 27. doi: 10.1001/jamaoncol.2023.0187. Online ahead of print.

ABSTRACT

IMPORTANCE: Biomarkers to guide the use of pertuzumab in the treatment of early-stage ERBB2 (formerly HER2)-positive breast cancer beyond simple ERBB2 status are needed.

OBJECTIVE: To determine if use of the HER2DX genomic assay (Reveal Genomics) in pretreatment baseline tissue samples of patients with ERBB2-positive breast cancer is associated with response to neoadjuvant trastuzumab-based chemotherapy with or without pertuzumab.

DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective diagnostic/prognostic analysis of a multicenter academic observational study in Spain performed during 2018 to 2022 (GOM-HGUGM-2018-05). In addition, a combined analysis with 2 previously reported trials of neoadjuvant cohorts with results from the assay (DAPHNe and I-SPY2) was performed. All patients had stage I to III ERBB2-positive breast cancer, signed informed consent, and had available formalin-fixed paraffin-embedded tumor specimens obtained prior to starting therapy.

EXPOSURES: Patients received intravenous trastuzumab, 8 mg/kg, loading dose, followed by 6 mg/kg every 3 weeks in combination with intravenous docetaxel, 75 mg/m2, every 3 weeks and intravenous carboplatin area under the curve of 6 every 3 weeks for 6 cycles, or this regimen plus intravenous pertuzumab, 840 mg, loading dose, followed by an intravenous 420-mg dose every 3 weeks for 6 cycles.

MAIN OUTCOME AND MEASURES: Association of baseline assay-reported pathologic complete response (pCR) score with pCR in the breast and axilla, as well as association of baseline assay-reported pCR score with response to pertuzumab.

RESULTS: The assay was evaluated in 155 patients with ERBB2-positive breast cancer (mean [range] age, 50.3 [26-78] years). Clinical T1 to T2 and node-positive disease was present in 113 (72.9%) and 99 (63.9%) patients, respectively, and 105 (67.7%) tumors were hormone receptor positive. The overall pCR rate was 57.4% (95% CI, 49.2%-65.2%). The proportion of patients in the assay-reported pCR-low, pCR-medium, and pCR-high groups was 53 (34.2%), 54 (34.8%), and 48 (31.0%), respectively. In the multivariable analysis, the assay-reported pCR score (as a continuous variable from 0-100) showed a statistically significant association with pCR (odds ratio [OR] per 10-unit increase, 1.43; 95% CI, 1.22-1.70; P < .001). The pCR rates in the assay-reported pCR-high and pCR-low groups were 75.0% and 28.3%, respectively (OR, 7.85; 95% CI, 2.67-24.91; P < .001). In the combined analysis (n = 282), an increase in pCR rate due to pertuzumab was found in the assay-reported pCR-high tumors (OR, 5.36; 95% CI, 1.89-15.20; P < .001) but not in the assay-reported pCR-low tumors (OR, 0.86; 95% CI, 0.30-2.46; P = .77). A statistically significant interaction between the assay-reported pCR score and the effect of pertuzumab in pCR was observed.

CONCLUSIONS AND RELEVANCE: This diagnostic/prognostic study demonstrated that the genomic assay predicted pCR following neoadjuvant trastuzumab-based chemotherapy with or without pertuzumab. This assay could guide therapeutic decisions regarding the use of neoadjuvant pertuzumab.

PMID:37103916 | DOI:10.1001/jamaoncol.2023.0187

J Clin Psychiatry. 2023 Apr 24;84(3):22m14739. doi: 10.4088/JCP.22m14739.

ABSTRACT

Objective: A post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled outpatient study investigated efficacy of lumateperone 42 mg in patients with bipolar I or bipolar II disorder and experiencing a major depressive episode (MDE) stratified by the presence of mixed features.

Methods: Adults (18-75 years) with bipolar I or bipolar II disorder experiencing an MDE, defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria, were randomized 1:1 to 6-week oral lumateperone 42 mg/d or placebo (conducted November 2017-March 2019). Montgomery-Asberg Depression Rating Scale (MADRS) total score, Clinical Global Impression Scale-Bipolar Version-Severity (CGI-BP-S) total score, and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) were analyzed in patients (N = 376) categorized as having mixed features (Young Mania Rating Scale [YMRS] score ≥ 4 and ≤ 12, 41.5%) or not having mixed features (YMRS < 4, 58.5%) at baseline. Treatment-emergent adverse events (TEAEs) including mania/hypomania were assessed.

Results: At day 43, lumateperone significantly improved MADRS and CGI-BP-S total scores change from baseline compared with placebo for patients with mixed features (MADRS least squares mean difference [LSMD] = -4.4, P < .01; CGI-BP-S LSMD = -0.7, P < .05) and without mixed features (MADRS LSMD = -4.2, P < .001, CGI-BP-S LSMD = -1.0, P < .001). Q-LES-Q-SF percent score significantly improved at day 43 with lumateperone vs placebo in patients with mixed features (LSMD = 5.9, P < .05), with numerical improvements in patients without mixed features (LSMD = 2.6, P = .27). TEAEs of mania/hypomania were rare.

Conclusions: Lumateperone 42 mg significantly improved symptoms of depression and disease severity in patients with an MDE associated with bipolar I or bipolar II disorder, with or without mixed features.

Trial Registration: ClinicalTrials.gov identifier: NCT03249376.

PMID:37103915 | DOI:10.4088/JCP.22m14739

J Robot Surg. 2023 Apr 27. doi: 10.1007/s11701-023-01604-z. Online ahead of print.

ABSTRACT

Da Vinci three-dimensional (3D) system has been increasingly used in customary surgical settings, gaining fundamental relevance for abdominal, urological, and gynecological laparoscopic surgery. The aim of this research is to evaluate the degree of discomfort and potential changes in the binocular vision and ocular motility of surgical operators, who employ 3D vision systems during Da Vinci robotic surgery. Twenty-four surgeons were enrolled in the study, including twelve who typically use the 3D Da Vinci system and twelve who routinely employ 2D system. Routine general ophthalmological and orthoptic examinations were conducted at baseline (T0), the day before surgery, and 30 min after the 3D or 2D surgery (T1). In addition, surgeons were interviewed using a questionnaire of 18 symptoms, with each item containing three questions regarding the frequency, severity, and bothersomeness of the symptoms, in order to evaluate the degree of discomfort. Mean age at evaluation was 45.28 ± 8.71 years (range 33-63 years). Cover test, uncover test, and fusional amplitude showed no statistically significant difference. After surgery, no statistical difference was observed in the Da Vinci group on the TNO stereotest (p > 0.9999). However, the difference in the 2D group resulted statistically significant (p = 0.0156). Comparing participants (p 0.0001) and time (T0-T1; p = 0.0137), the difference between the two groups was statistically significant. Surgeons using 2D systems reported more discomfort than those using 3D systems. The absence of short-term consequences following surgery with the Da Vinci 3D system is a promising conclusion, considering the numerous advantages of this technology. Nonetheless, multicenter investigations and more studies are required to verify and interpret our findings.

PMID:37103772 | DOI:10.1007/s11701-023-01604-z

Indian J Gastroenterol. 2023 Apr 27. doi: 10.1007/s12664-022-01330-8. Online ahead of print.

ABSTRACT

BACKGROUND: Due to the increasing prevalence of non-alcoholic fatty liver disease (NAFLD), there was a need to establish non-invasive tests for its detection. Mean platelet volume (MPV) is an inexpensive, practical and easily accessible marker of inflammation in many disorders. Our study was aimed at investigating the relationship between MPV and both NAFLD and liver histology.

METHODS: Total 290 patients with biopsy-proven NAFLD (n = 124) and 108 control patients were included in the study. To exclude the effect of other diseases on MPV, we included 156 patient controls in our study. Those whohave liver-related diseases and those who use drugs that may cause fatty liver were not included in the study. Liver biopsy was performed for those whose alanine aminotransferase level persisted for >6 months above the upper limits.

RESULTS/CONCLUSION: We found that MPV was significantly higher in the NAFLD group compared with the control group, and MPV had an independent predictive value for the development of NAFLD. We determined that the number of platelets was significantly lower in the NAFLD group compared with that in the control group. We compared MPV values histologically with both stage and grade in all patients with biopsy-proven NAFLD and found that MPV had a significant positive correlation with stage. We observed a positive correlation between MPV and non-alcoholic steatohepatitis grade, but this was not statistically significant. MPV can be useful because it is simple, easy to measure, cost-effective, and routinely tested in daily practice. MPV can be used as a simple marker of NAFLD and an indicator of fibrosis-stage in NAFLD.

PMID:37103751 | DOI:10.1007/s12664-022-01330-8

Breast Cancer. 2023 Apr 27. doi: 10.1007/s12282-023-01459-0. Online ahead of print.

ABSTRACT

OBJECTIVE: We aim to use the SEER database to discuss the effect of various surgical methods of primary foci and other influencing factors on the nonregional lymph node (NRLN) metastasis in invasive ductal carcinoma (IDC) patients.

METHODS: Clinical information of IDC patients used in this study was obtained from the SEER database. The statistical analyses used included a multivariate logistic regression model, the chi-squared test, log-rank test and propensity score matching (PSM).

RESULTS: 243,533 patients were included in the analysis. 94.3% of NRLN patients had a high N positivity (N3) but an equal distribution in T status. The proportion of operation type, especially BCM and MRM, differed significantly between the N0-N1 and N2-N3 groups in the NRLN metastasis group and nonmetastasis group. Age > 80 years, positive PR, modified radical mastectomy (MRM)/radical mastectomy (RM) and radiotherapy for primary tumor were shown to be protective factors for NRLN metastasis, and higher N positivity was the most significant risk factors. N2-N3 patients receiving MRM had a lower metastasis to NRLN than those receiving BCM (1.4% vs 3.7%, P < 0.001), while this relevance was not discovered in N0-N1 patients. In N2-N3 patients, a better OS was observed in MRM group than BCM group (P < 0.001).

CONCLUSION: MRM exerted a protective effect on NRLN metastasis compared to BCM in N2-N3 patients but not N0-N1 patients. This implies the need for more consideration when choosing the operation methods of primary foci in patients with high N positivity.

PMID:37103742 | DOI:10.1007/s12282-023-01459-0

Environ Sci Pollut Res Int. 2023 Apr 27. doi: 10.1007/s11356-023-27190-z. Online ahead of print.

ABSTRACT

This paper focuses on the spatiotemporal evolution characteristics, as well as the driving factors, of carbon emissions in the prefecture-level cities in the Yellow River Basin (YB). The paper’s findings will aid in promoting ecological conservation and high-quality development in the region. The initiatives undertaken in the YB are a significant national strategy towards achieving carbon peaking and carbon neutrality. To fully investigate the spatiotemporal evolution process, as well as the typical characteristics of their carbon emissions, conventional, and spatial Markov transition probability matrices were developed utilizing YB’s panel data for 55 prefecture-level cities from 2003 to 2019. The generalized Divisia index decomposition method (GDIM) cleverly uses this data to conduct a complete analysis of the dynamics and driving processes influencing the change in carbon emissions in these cities. However, the evolution of carbon emissions in prefecture-level cities has reached a point of stability that maintains the original state, making it challenging to make meaningful short-term progress. The data indicates that prefecture-level cities in the YB are emitting more carbon dioxide on average. Neighborhood types in these cities significantly influence the transformation of carbon emissions. Low-emission areas can encourage a reduction in carbon emissions, whereas high-emission areas can encourage an increase. The spatial organisation of carbon emissions exhibits a “high-high convergence, low-low convergence, high-pulling low, low-inhibiting high” club convergence phenomenon. Carbon emissions rise with per capita carbon emissions, energy consumed, technology, and output scale, whereas it falls with carbon technology intensity and output carbon intensity. Hence, instead of enhancing the role of increase-oriented variables, prefecture-level cities in the YB should actively engage these reduction-oriented forces. The YB’s key pathways for lowering carbon emissions include boosting research and development, promoting and applying carbon emission reduction technologies, lowering output carbon intensity and energy intensity, and improving energy use effectiveness.

PMID:37103708 | DOI:10.1007/s11356-023-27190-z

Environ Sci Pollut Res Int. 2023 Apr 27. doi: 10.1007/s11356-023-27147-2. Online ahead of print.

ABSTRACT

An understanding of the vertical variations in hydrogeochemical processes in various aquifers and quality suitability assessment is crucial for the utilization of groundwater in the Ningtiaota coalfield of Ordos Basin, Northwestern China. Based on 39 water samples collected from surface water (SW), Quaternary pore water (QW), weathered fissure water (WW), and mine water (MW), we conducted self-organizing maps (SOM) algorithm, multivariate statistical analysis (MSA), and classical graphical methods to elucidate the mechanisms controlling the vertical spatial variations in SW and groundwater chemistry and conducted a health risk assessment. The findings indicated that the hydrogeochemical type showed a transition from the HCO₃^–-Na⁺ type in SW to the HCO₃^–-Ca²⁺ type in QW, then to the SO₄^2--Mg²⁺ type in WW, and back to HCO₃^–-Na⁺ type in MW. Water-rock interaction, silicate dissolution, and cation exchange were the main hydrogeochemical processes in the study area. Additionally, groundwater residence time and mining operations were critical external factors that affect water chemistry. Contrary to phreatic aquifers, confined aquifers featured greater circulation depth, water-rock interactions, and external interventions leading to worse quality and higher health risks. Water quality surrounding the coalfield was poor, causing it to be undrinkable, with excessive SO₄^2-, arsenic (As), and F^–, etc. Approximately 61.54% of SW, all of QW, 75% of WW, and 35.71% of MW can be used for irrigation.

PMID:37103707 | DOI:10.1007/s11356-023-27147-2

Sleep Breath. 2023 Apr 27. doi: 10.1007/s11325-023-02835-y. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to examine the relationship between plasma metabolites (biochemical parameters) and comorbid illnesses with sleep quality in individuals with coronary heart disease (CHD).

METHODS: This descriptive cross-sectional study was conducted between 2020 and 2021 at a university hospital. Hospitalized patients with a diagnosis of CHD were analyzed. The Personal Information Form’ and Pittsburgh Sleep Quality Index (PSQI) were used to collect data. Laboratory findings including plasma metabolites were examined.

RESULTS: Of 60 hospitalized patients with CHD, 50 (83%) had poor sleep quality. A positive and statistically significant correlation was found between the plasma metabolite blood urea nitrogen and poor sleep quality (r = 0.399; p = 0.002). The presence of CHD and additional chronic diseases (especially diabetes mellitus, hypertension, and chronic kidney disease) are important parameters associated with the risk of poor sleep quality (p = 0.040 < 0.05).

CONCLUSION: Increases in blood urea nitrogen level in individuals with CHD are associated with worse sleep quality. Additional chronic diseases coexisting with CHD correlate with increased risk of poor sleep quality.

PMID:37103681 | DOI:10.1007/s11325-023-02835-y

Clin Exp Med. 2023 Apr 27. doi: 10.1007/s10238-023-01073-6. Online ahead of print.

ABSTRACT

Idiopathic inflammatory myopathy (IIM) are heterogeneous autoimmune diseases that primarily affect the proximal muscles. IIM subtypes include dermatomyositis (DM), polymyositis (PM), and anti-synthetase syndrome (ASS). Metabolic disturbances may cause irreversible structural damage to muscle fibers in patients with IIM. However, the metabolite profile of patients with different IIM subtypes remains elusive. To investigate metabolic alterations and identify patients with different IIM subtypes, we comprehensively profiled plasma metabolomics of 46 DM, 13 PM, 12 ASS patients, and 30 healthy controls (HCs) using UHPLC-Q Exactive HF mass spectrometer. Multiple statistical analyses and random forest were used to discover differential metabolites and potential biomarkers. We found that tryptophan metabolism, phenylalanine and tyrosine metabolism, fatty acid biosynthesis, beta-oxidation of very long chain fatty acids, alpha-linolenic acid and linoleic acid metabolism, steroidogenesis, bile acid biosynthesis, purine metabolism, and caffeine metabolism are all enriched in the DM, PM, and ASS groups. We also found that different subtypes of IIM have their unique metabolic pathways. We constructed three models (five metabolites) to identify DM, PM, ASS from HC in the discovery and validation sets. Five to seven metabolites can distinguish DM from PM, DM from ASS, and PM from ASS. A panel of seven metabolites can identify anti-melanoma differentiation-associated gene 5 positive (MDA5 +) DM with high accuracy in the discovery and validation sets. Our results provide potential biomarkers for diagnosing different subtypes of IIM and a better understanding of the underlying mechanisms of IIM.

PMID:37103652 | DOI:10.1007/s10238-023-01073-6

Clin Exp Med. 2023 Apr 27. doi: 10.1007/s10238-023-01082-5. Online ahead of print.

ABSTRACT

The role of anti-thyroid peroxidase antibodies (anti-TPO Abs) in the development of abnormal thyroid function tests (DYSTHYR) during treatment with immune checkpoint inhibitors (ICIs) is not fully understood; moreover, controversial data exist about the relationship between ICI-related thyroid dysfunction (TD) and survival. We retrospectively analyzed the onset or the worsening of DYSTHYR in patients treated with programmed cell death protein-1 (PD-1) or its ligand (PD-L1) inhibitors between 2017 and 2020. In patients without previous TD, we focused on the association between baseline anti-TPO Abs level and DYSTHYR. Furthermore, the relationship between DYSTHYR and progression-free survival (PFS) or overall survival (OS) was explored. We included 324 patients treated with anti PD-1 (95.4%) or anti PD-L1 inhibitors. After a median of 3.3 months, DYSTHYR was registered in 24.7%, mostly hypothyroidism alone (17%). Patients with pre-existing TD (14.5% of the sample) were at higher risk of DYSTHYR compared to patients without previous TD (adjusted OR 2.44; 95% IC 1.26-4.74). In patients without known previous TD, high anti-TPO Abs level, even below the positivity cut-off, was a risk factor for developing DYSTHYR (adjusted OR 5.52; 95% IC 1.47-20.74). DYSTHYR was associated with a longer 12-month OS (87.3% vs 73.5%, p = 0.03); no statistically significant difference in terms of PFS was observed between the DYSTHYR+ and DYSTHYR- group. DYSTHYR is common during anti PD-1/anti PD-L1 treatment, especially in patients with pre-existing TD. In subjects without known previous TD, high anti-TPO Abs level at baseline can be a predictive biomarker of DYSTHYR. An improved OS is observed in patients with anti PD-1/anti PD-L1-induced DYSTHYR.

PMID:37103651 | DOI:10.1007/s10238-023-01082-5