Nevin Manimala

Strahlenther Onkol. 2022 Jan 17. doi: 10.1007/s00066-021-01890-2. Online ahead of print.

ABSTRACT

PURPOSE: About one fifth of patients with head and neck cancer are aged 70 years and older at the time of diagnosis. In these patients, risk factors (R1 status or extracapsular extension of lymph node metastases, ECE) often lead to a need for combined chemoradiotherapy (CRT) in the postoperative setting. However, there is considerable concern about the toxicity of such therapy in this age group.

METHODS: Retrospective evaluation of the data of 53 patients ≥ 70 years of age who underwent surgery in our hospital between 1999 and 2015 for tumors of the oral cavity, the oropharynx, the hypopharynx, or the larynx, who subsequently received adjuvant radiation therapy. Two younger patients (< 70 years) were assigned to each of the elderly patients in a matching procedure based on anatomic sublocalization and tumor stage. The total cohort was comprised of 154 patients.

RESULTS: Univariate analyses revealed a statistically significant influence of many factors on overall survival (OS) and progression-free survival (PFS), including Karnofsky performance score (KPS), alcohol consumption, smoking, R status, ECE, chemotherapy, and discontinuation of RT. Younger patients had better OS and PFS compared to the elderly (p = 0.013 and 0.012, respectively). In a multivariate Cox regression, no independent influence of age on OS and PFS was found. Survival was primarily dependent on the addition of chemotherapy to radiotherapy (RT), application of the full course of RT, continued alcohol abuse, KPS, and the presence of ECE. Toxicity analysis showed a higher incidence of chronic renal failure but, generally, side effects for elderly patients were not substantially greater.

CONCLUSION: Performance status and behavioral risk factors but not chronological age are crucial for the prognosis of patients who require adjuvant chemoradiation.

PMID:35037950 | DOI:10.1007/s00066-021-01890-2

PeerJ. 2022 Jan 5;10:e12715. doi: 10.7717/peerj.12715. eCollection 2022.

ABSTRACT

BACKGROUND: Improved detection of hepatocellular carcinoma (HCC) is needed, as current detection methods, such as alpha fetoprotein (AFP) and ultrasound, suffer from poor sensitivity. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate many cellular functions and impact cancer development and progression. Notably, miRNAs are detectable in saliva and have shown potential as non-invasive biomarkers for a number of cancers including breast, oral, and lung cancers. Here, we present, to our knowledge, the first report of salivary miRNAs in HCC and compare these findings to patients with cirrhosis, a high-risk cohort for HCC.

METHODS: We performed small RNA sequencing in 20 patients with HCC and 19 with cirrhosis. Eleven patients with HCC had chronic liver disease, and analyses were performed with these samples combined and stratified by the presence of chronic liver disease. P values were adjusted for multiple comparisons using a false discovery rate (FDR) approach and miRNA with FDR P < 0.05 were considered statistically significant. Differential expression of salivary miRNAs was compared to a previously published report of miRNAs in liver tissue of patients with HCC vs cirrhosis. Support vector machines and leave-one-out cross-validation were performed to determine if salivary miRNAs have predictive potential for detecting HCC.

RESULTS: A total of 4,565 precursor and mature miRNAs were detected in saliva and 365 were significantly different between those with HCC compared to cirrhosis (FDR P < 0.05). Interestingly, 283 of these miRNAs were significantly downregulated in patients with HCC. Machine-learning identified a combination of 10 miRNAs and covariates that accurately classified patients with HCC (AUC = 0.87). In addition, we identified three miRNAs that were differentially expressed in HCC saliva samples and in a previously published study of miRNAs in HCC tissue compared to cirrhotic liver tissue.

CONCLUSIONS: This study demonstrates, for the first time, that miRNAs relevant to HCC are detectable in saliva, that salivary miRNA signatures show potential to be highly sensitive and specific non-invasive biomarkers of HCC, and that additional studies utilizing larger cohorts are needed.

PMID:35036096 | PMC:PMC8742548 | DOI:10.7717/peerj.12715

PeerJ. 2022 Jan 3;10:e12690. doi: 10.7717/peerj.12690. eCollection 2022.

ABSTRACT

BACKGROUND AND OBJECTIVES: Globally, the prevalence of hypertension (HTN) with the coexistence of chronic kidney disease (CKD) is increasing, resulting in poor quality of life. The main objective of the study was to measure the health-related quality of life (HRQoL) of hypertensive hemodialysis patients.

METHODS: A multicenter follow-up study was carried out in six public and two private dialysis centers in Pakistan. A total of 517 hypertensive hemodialysis patients responded by completing the questionnaire at baseline and two subsequent phases. The quality of life of these patients was assessed using the EQ-5D-5L questionnaire (a standardized instrument for measuring generic health status). Statistical analysis was done using a multivariate linear regression model, Friedman test and Kruskal Wallis test.

RESULTS: The majority of patients (58.2%) had normal body mass index and about 60.5% of the patients were taking less salt due to HTN. Friedman test gave the statistically significant results (p ≤ 0.001) in systolic blood pressure (BP), diastolic BP and EQ-5D visual analogue scale (VAS) score between three phases (initial visit, first follow-up and second follow-up). A significant improvement was observed in self-care and usual activities from initial visit to first follow-up (p < 0.05). The most problematic dimension among the hypertensive patients with CKD was pain/discomfort (86.5%).

CONCLUSIONS: HTN with coexisting CKD in hemodialysis patients severely affected HRQoL. Pain/discomfort was the most problematic dimension among the participants.

PMID:35036092 | PMC:PMC8734469 | DOI:10.7717/peerj.12690

PeerJ. 2022 Jan 5;10:e12607. doi: 10.7717/peerj.12607. eCollection 2022.

ABSTRACT

BACKGROUND: Chrysanthemum is a popular ornamental and medicinal plant that suffers from many viruses and viroids. Among them, chrysanthemum virus B (CVB, genus Carlavirus, family Betaflexiviridae) is widespread in all chrysanthemum-growing regions. Another carlavirus, chrysanthemum virus R (CVR), has been recently discovered in China. Information about chrysanthemum viruses in Russia is very scarce. The objective of this work was to study the prevalence and genetic diversity of CVB and CVR in Russia.

METHODS: We surveyed the chrysanthemum (Chrysanthemum morifolium Ramat.) germplasm collection in the Nikita Botanical Gardens, Yalta, Russia. To detect CVB and CVR, we used RT-PCR with virus-specific primers. To reveal the complete genome sequences of CVB and CVR isolates, metatransciptomic analysis of the cultivars Ribonette, Fiji Yellow, and Golden Standard plants, naturally co-infected with CVB and CVR, was performed using Illumina high-throughput sequencing. The recombination detection tool (RDP4) was employed to search for recombination in assembled genomes.

RESULTS: A total of 90 plants of 23 local and introduced chrysanthemum cultivars were surveyed. From these, 58 and 43% plants tested positive for CVB and CVR, respectively. RNA-Seq analysis confirmed the presence of CVB and CVR, and revealed tomato aspermy virus in each of the three transcriptomes. Six near complete genomes of CVB and CVR were assembled from the RNA-Seq reads. The CVR isolate X21 from the cultivar Golden Standard was 92% identical to the Chinese isolate BJ. In contrast, genomes of the CVR isolates X6 and X13 (from the cultivars Ribonette and Fiji Yellow, respectively), were only 76% to 77% identical to the X21 and BJ, and shared 95% identity to one another and appear to represent a divergent group of the CVR. Two distantly related CVB isolates, GS1 and GS2, were found in a plant of the cultivar Golden Standard. Their genomes shared from 82% to 87% identity to each other and the CVB genome from the cultivar Fiji Yellow (isolate FY), as well as to CVB isolates from Japan and China. A recombination event of 3,720 nucleotides long was predicted in the replicase gene of the FY genome. It was supported by seven algorithms implemented in RDP4 with statistically significant P-values. The inferred major parent was the Indian isolate Uttar Pradesh (AM765837), and minor parent was unknown.

CONCLUSION: We found a wide distribution of CVB and CVR in the chrysanthemum germplasm collection of the Nikita Botanical Gardens, which is the largest in Russia. Six near complete genomes of CVR and CVB isolates from Russia were assembled and characterized for the first time. This is the first report of CVR in Russia and outside of China thus expanding the information on the geographical distribution of the virus. Highly divergent CVB and CVR isolates have been identified that contributes the better understanding the genetic diversity of these viruses.

PMID:35036085 | PMC:PMC8742542 | DOI:10.7717/peerj.12607

PeerJ. 2022 Jan 4;10:e12568. doi: 10.7717/peerj.12568. eCollection 2022.

ABSTRACT

BACKGROUND: Malignant mesothelioma (MM) is a rare and highly aggressive cancer. Despite advances in multidisciplinary treatments for cancer, the prognosis for MM remains poor with no effective diagnostic biomarkers currently available. The aim of this study was to identify plasma metabolic biomarkers for better MM diagnosis and prognosis by use of a MM cell line-derived xenograft (CDX) model.

METHODS: The MM CDX model was confirmed by hematoxylin and eosin staining and immunohistochemistry. Twenty female nude mice were randomly divided into two groups, 10 for the MM CDX model and 10 controls. Plasma samples were collected two weeks after tumor cell implantation. Gas chromatography-mass spectrometry analysis was conducted. Both univariate and multivariate statistics were used to select potential metabolic biomarkers. Hierarchical clustering analysis, metabolic pathway analysis, and receiver operating characteristic (ROC) analysis were performed. Additionally, bioinformatics analysis was used to investigate differential genes between tumor and normal tissues, and survival-associated genes.

RESULTS: The MM CDX model was successfully established. With VIP > 1.0 and P-value < 0.05, a total of 23 differential metabolites were annotated, in which isoleucine, 5-dihydrocortisol, and indole-3-acetamide had the highest diagnostic values based on ROC analysis. These were mainly enriched in pathways for starch and sucrose metabolism, pentose and glucuronate interconversions, galactose metabolism, steroid hormone biosynthesis, as well as phenylalanine, tyrosine and tryptophan biosynthesis. Further, down-regulation was observed for amino acids, especially isoleucine, which is consistent with up-regulation of amino acid transporter genes SLC7A5 and SLC1A3 in MM. Overall survival was also negatively associated with SLC1A5, SLC7A5, and SLC1A3.

CONCLUSION: We found several altered plasma metabolites in the MM CDX model. The importance of specific metabolic pathways, for example amino acid metabolism, is herein highlighted, although further investigation is warranted.

PMID:35036082 | PMC:PMC8740518 | DOI:10.7717/peerj.12568

PeerJ. 2022 Jan 4;10:e12493. doi: 10.7717/peerj.12493. eCollection 2022.

ABSTRACT

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a tumor that frequently shows the hematogenous pathway and tends to be resistant to radiotherapy and chemotherapy. However, the exact mechanism of ccRCC metastasis remains unknown.

METHODS: Differentially expressed genes (DEGs) of three gene expression profiles (GSE85258, GSE105288 and GSE22541) downloaded from the Gene Expression Omnibus (GEO) database were analyzed by GEO2R analysis, and co-expressed DEGs among the datasets were identified using a Venn drawing tool. The co-expressed DEGs were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and hub genes were determined based on the protein-protein interaction network established by STRING. After survival analysis performed on UALCAN website, possible key genes were selected and verified in ccRCC cell lines and ccRCC tissues (n = 44). Statistical analysis was conducted using GraphPad Prism (Version 8.1.1).

RESULTS: A total of 104 co-expressed DEGs were identified in the three datasets. Pathway analysis revealed that these genes were enriched in the extracellular matrix (ECM)-receptor interaction, protein digestion and absorption and focal adhesion. Survival analysis on 17 hub genes revealed that four key genes with a significant impact on survival: procollagen C-endopeptidase enhancer (PCOLCE), prolyl 4-hydroxylase subunit beta (P4HB), collagen type VI alpha 2 (COL6A2) and collagen type VI alpha 3 (COL6A3). Patients with higher expression of these key genes had worse survival than those with lower expression. In vitro experiments revealed that the mRNA expression levels of PCOLCE, P4HB and COL6A2 were three times higher and that of COL6A3 mRNA was 16 times higher in the metastatic ccRCC cell line Caki-1 than the corresponding primary cell line Caki-2. Immunohistochemistry revealed higher expression of the proteins encoded by these four genes in metastatic ccRCC compared with tumors from the corresponding primary sites, with statistical significance.

CONCLUSION: PCOLCE, P4HB, COL6A2 and COL6A3 are upregulated in metastatic ccRCC and might be related to poor prognosis and distant metastases.

PMID:35036081 | PMC:PMC8740509 | DOI:10.7717/peerj.12493

Int J Nephrol. 2022 Jan 6;2022:1148378. doi: 10.1155/2022/1148378. eCollection 2022.

ABSTRACT

BACKGROUND: There is very little published data on outcomes of COVID-19 among chronic kidney disease (CKD) patients. We compared the outcomes of COVID-19 in a tertiary care renal hospital among CKD V patients on hemodialysis (HD), peritoneal dialysis (PD), and dialysis initiation, in terms of duration of hospitalization, in-patient mortality, and 30-day mortality.

METHODS: A total of 436 CKD V patients, on either HD, PD, or dialysis initiation, with COVID-19 who were admitted at the National Kidney and Transplant Institute (NKTI) from March 13, 2020, to August 31, 2020, were included. Kaplan-Meier survival analysis was performed. Comparison of probability of mortality by group was performed using Log-Rank test. p values ≤0.05 were considered statistically significant.

RESULTS: Among 436 CKD V patients, 298 (68%) were on HD, 103 (24%) were on PD, and 35 (8%) required dialysis initiation. Overall in-hospital mortality was 34%; 38% were on HD, 20% on PD, and 37% on dialysis initiation. Total 30-day mortality was 27%; 32% were on HD, 26% on PD, and 16% on dialysis initiation. Median follow-up was 24 days. Among the 137 deaths recorded, total median time to death was 10 days; 8.5 days, 15.5 days, and 9 days for HD, PD, and dialysis initiation groups, respectively. Probability of mortality was significantly higher in HD patients versus PD patients (p < 0.00001) and in the dialysis initiation group compared to PD patients (p=0.0234). Mortality probability, however, was not significantly different in HD patients versus the dialysis initiation group (p=0.63).

CONCLUSION: Among CKD V patients diagnosed with COVID-19 at the NKTI, those on HD and on dialysis initiation had significantly higher in-hospital and 30-day mortality, compared to patients on PD.

PMID:35036007 | PMC:PMC8758287 | DOI:10.1155/2022/1148378

J Nutr Metab. 2022 Jan 7;2022:2661912. doi: 10.1155/2022/2661912. eCollection 2022.

ABSTRACT

Loss of appetite (LOA) may have a negative impact on a patient’s well-being owing to loss of nutrition and associated conditions. The current study assessed the effects of an appetite-stimulating medication containing multivitamins, lysine, and zinc in Indian patients with a history of LOA. Using an investigator-initiated, single-center, open-label, single-arm design, we evaluated the effectiveness and safety of the appetite-stimulating medication (15 mL) in 50 male or female patients (18-55 years old) attending the outpatient department, with a confirmed diagnosis of LOA after two weeks of therapy and assessed the change in Council on Nutrition Appetite Questionnaire (CNAQ) score and safety of the medication after two weeks of treatment. CNAQ scores were presented as mean (standard deviation (SD)). The mean age of patients was 42.1 years, with the majority (66%) being males. At weeks 1 and 2, a statistically significant improvement was observed in the mean CNAQ scores of 25.48 (5.10) and 25.48 (4.29), respectively, vs. baseline (22.08 (2.76); P ≤ 0.0001 both). Majority of the patients had CNAQ appetite scores of 17-28 at baseline (94%), week 1 (66%), and week 2 (78%) of treatment. For patients with acute and chronic illness, a statistically significant improvement was observed in the mean CNAQ score at week 1 (26.75 (3.69), P = 0.0256; 25.24 (5.33), P = 0.0004) and at week 2 (26.63 (3.46), P = 0.0027; 25.26 (4.43), P ≤ 0.0001) from baseline (21.88 (3.31) and 22.12 (2.69), respectively). No serious adverse events were reported during the study. The study findings suggest that appetite-stimulating medication containing multivitamins, lysine, and zinc could be a suitable treatment option for the management of LOA with no significant safety concerns.

PMID:35036004 | PMC:PMC8759923 | DOI:10.1155/2022/2661912

J Ophthalmol. 2022 Jan 7;2022:1703806. doi: 10.1155/2022/1703806. eCollection 2022.

ABSTRACT

PURPOSE: To analyze ocular manifestations, visual field (VF) pattern, and VF test performance in traumatic brain injury (TBI) and stroke patients.

METHODS: This retrospective, cross-sectional study included 118 patients (236 eyes) with TBI and stroke who had undergone VF testing by standard automated perimetry with the central 24-2 threshold test. Clinical features including best-corrected visual acuity (BCVA), intraocular pressure (IOP), ocular manifestations, and VF test results including VF defect pattern, reliability, and global indices were analyzed and compared between the TBI and stroke patients.

RESULTS: In TBI patients, ocular manifestations included strabismus (11.1%), cataract (4.2%), and glaucoma suspect (2.8%), whereas in stroke patients, cataract (15.2%), strabismus (8.5%), diabetic retinopathy (4.9%), extraocular movement (EOM) limitation (3.0%), glaucoma suspect (3.0%), nystagmus (2.4%), drusen (1.2%), and vitreous hemorrhage (1.2%) were found. The VF test results showed that 47 eyes (85.5%) in TBI and 86 (65.2%) in stroke had VF defect; in TBI, the scattered pattern was the most common (56.4%), followed by homonymous hemianopsia (14.5%), homonymous quadrantanopia (10.9%), and total defect (3.6%), whereas in stroke, homonymous hemianopsia was the most common (31.8%), followed by scattered pattern (16.7%), homonymous quadrantanopia (12.1%), and total defect (4.5%). Only 15 eyes (27.3%) in TBI and 32 (24.2%) in stroke showed reliable VF indices. The mean deviation (MD) was -10.5 ± 7.1 dB in TBI and -9.5 ± 6.8 dB in stroke, and the pattern standard deviation (PSD) was 4.9 ± 3.3 dB in TBI and 6.1 ± 3.9 dB in stroke, without statistically significant differences between the two groups.

CONCLUSION: Various ocular manifestations were found, and a considerable proportion of patients were experiencing VF defects and showed unreliable VF test performance. Our findings suggest that accurate evaluation and rehabilitation of visual function should be a matter of greater concern and emphasis in the management of TBI and stroke patients, besides systemic diseases.

PMID:35036002 | PMC:PMC8759901 | DOI:10.1155/2022/1703806