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2022 ◽  
Vol 20 (6) ◽  
pp. 78-87
Author(s):  
Ya. G. Murazov ◽  
A. L. Semenov ◽  
K. Yu. Senchik ◽  
A. O. Nyuganen ◽  
A. S. Artemyeva ◽  
...  

In our study we carried out an exploratory assessment of the antitumor activity of hyperthermic intraperitoneal perfusion (Hipep) with 0.9 % sodium chloride solution and compared it with the effect of a single normothermic intraperitoneal (i.p.) Administration of cisplatin in the maximum tolerated dose (mtd). Thirty-six mature female Wistar rats with transplanted i.p. Syngeneic ovarian carcinoma were randomized into three groups: control group (2 ml of 0.9 % sodium chloride i.p. At room temperature, n=12); cisplatin group (cisplatin 4 mg/kg i.p. At room temperature, n=12); Hipep group (open i.p. Perfusion with 0.9 % sodium chloride solution at a temperature of 40,5–41,5 °c for 45 minutes, n=12). The primary endpoint was the overall survival (os) of the animals in each of the three groups. The total peritoneal cancer index (pci), weight and degree of ascites haemorrhagia were assessed at autopsy. The median os in the control group, Hipep, and cisplatin was 19, 39, and 40 days, respectively (log-rank test р<0.0001). In comparison to the control group, the differences were statistically significant for both cisplatin (HR=0.22; 95 % ci: 0.08–0.62; log-rank test р<0.0001) and Hipep (HR=0.32; 95 % ci 0.13–0.82; log-rank test р=0.0013). There were no differences in os between the cisplatin and Hipep groups (log-rank test р=0.4853). The Hipep procedure was associated with a significant decrease in total pci, a tendency towards a decrease in the ascites weight and a higher severity of haemorrhagia. In terms of os, local hyperthermia, provided by Hipep without a cytostatic drug, was comparable with single normothermic i.p. Administration of cisplatin in mtd and exceeded the effects of the latter in relation to the development of peritoneal carcinomatosis.


Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 331
Author(s):  
Tomoyasu Mimori ◽  
Takehito Shukuya ◽  
Ryo Ko ◽  
Yusuke Okuma ◽  
Tomonobu Koizumi ◽  
...  

The optimal tumor marker for predicting the prognosis of advanced thymic carcinoma (ATC) remains unclear. We conducted a multi-institutional retrospective study of patients with ATC. A total of 286 patients were treated with chemotherapy. Clinicopathological information, including serum tumor markers, was evaluated to determine the overall survival (OS) and progression-free survival (PFS). The carcinoembryonic antigen, cytokeratin-19 fragment, squamous cell carcinoma (SCC) antigen, progastrin-releasing peptide, neuron-specific enolase (NSE), and alpha-fetoprotein levels were evaluated. In the Kaplan–Meier analysis, the OS was significantly shorter in the patients with elevated NSE levels than in those with normal NSE levels (median, 20.3 vs. 36.8 months; log-rank test p = 0.029; hazard ratio (HR), 1.55; 95% confidence interval (CI), 1.05–2.31 (Cox proportional hazard model)); a similar tendency regarding the PFS was observed (median, 6.4 vs. 11.0 months; log-rank test p = 0.001; HR, 2.04; 95% CI, 1.31–3.18). No significant differences in the OS and PFS were observed among the other tumor markers. In both univariate and multivariate analyses of the patients with SCC only, the NSE level was associated with the OS and PFS. Thus, the NSE level may be a prognostic tumor marker for thymic carcinoma, regardless of histology.


2022 ◽  
Vol 2022 ◽  
pp. 1-12
Author(s):  
Natsumi Matsuoka-Uchiyama ◽  
Haruhito A. Uchida ◽  
Shugo Okamoto ◽  
Yasuhiro Onishi ◽  
Katsuyoshi Katayama ◽  
...  

Objective. We examined whether or not day-to-day variations in lipid profiles, especially triglyceride (TG) variability, were associated with the exacerbation of diabetic kidney disease. Methods. We conducted a retrospective and observational study. First, 527 patients with type 2 diabetes mellitus (DM) who had had their estimated glomerular filtration rate (eGFR) checked every 6 months since 2012 for over 5 years were registered. Variability in postprandial TG was determined using the standard deviation (SD), SD adjusted (Adj-SD) for the number of measurements, and maximum minus minimum difference (MMD) during the first three years of follow-up. The endpoint was a ≥40% decline from baseline in the eGFR, initiation of dialysis or death. Next, 181 patients who had no micro- or macroalbuminuria in February 2013 were selected from among the 527 patients for an analysis. The endpoint was the incidence of microalbuminuria, initiation of dialysis, or death. Results. Among the 527 participants, 110 reached a ≥40% decline from baseline in the eGFR or death. The renal survival was lower in the higher-SD, higher-Adj-SD, and higher-MMD groups than in the lower-SD, lower-Adj-SD, and lower-MMD groups, respectively (log-rank test p = 0.0073 , 0.0059, and 0.0195, respectively). A lower SD, lower Adj-SD, and lower MMD were significantly associated with the renal survival in the adjusted model (hazard ratio, 1.62, 1.66, 1.59; 95% confidence intervals, 1.05-2.53, 1.08-2.58, 1.04-2.47, respectively). Next, among 181 participants, 108 developed microalbuminuria or death. The nonincidence of microalbuminuria was lower in the higher-SD, higher-Adj-SD, and higher-MMD groups than in the lower-SD, lower-Adj-SD, and lower-MMD groups, respectively (log-rank test p = 0.0241 , 0.0352, and 0.0474, respectively). Conclusions. Postprandial TG variability is a novel risk factor for eGFR decline and the incidence of microalbuminuria in patients with type 2 DM.


2022 ◽  
Vol 11 (2) ◽  
pp. 297
Author(s):  
Nobuhiro Asai ◽  
Yuichi Shibata ◽  
Daisuke Sakanashi ◽  
Hideo Kato ◽  
Mao Hagihara ◽  
...  

(1) Introduction: Evidence-based medicine (EBM) is necessary to standardize treatments for infections because EBM has been established based on the results of clinical trials. Since entry criteria for clinical trials are very strict, it may cause skepticism or questions on whether the results of clinical trials reflect the real world of medical practice. (2) Methods: To examine how many patients could join any randomized clinical trials for the treatment of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP). We reviewed all the pneumonia patients in our institute during 2014–2017. The patients were divided into two groups: patients who were eligible for clinical trials (participation-possible group), and those who were not (participation-impossible group). Exclusion criteria for clinical trials were set based on previous clinical trials. (3) Results: A total of 406 patients were enrolled in the present study. Fifty-seven (14%) patients were categorized into the participation-possible group, while 86% of patients belonged to the participation-impossible group. Patients in the participation-possible group had less comorbidities and more favorable outcomes than those with the participation-impossible group. As for the outcomes, there were significant differences in the 30-day and in-hospital mortality rates between the two groups. In addition, the participation-possible group showed a longer overall survival time than the participation-impossible group (p < 0.001 by Log-Rank test). (4) Conclusion: There is a difference in patients’ profile and outcomes between clinical trials and the real world. Though EBM is essential to advance medicine, we should acknowledge the facts and the limits of the clinical trials.


2022 ◽  
Vol 35 (1) ◽  
pp. 111-112
Author(s):  
Shi-wei Li ◽  
Tao Yao ◽  
Li Zhang ◽  
Lei Zhao ◽  
Xiao-ling Zhang ◽  
...  

Abstract Background To investigate the effect of brachial–ankle pulse wave velocity (baPWV) on new-onset acute myocardial infarction (AMI). Methods A retrospective cohort study was performed for the subjects who underwent baPWV examination during the follow-up of Kailuan Study Cohort from 2010 to 2017. The observation subjects were divided into 3 groups based on the levels of baPWV: &lt;14, 14 to &lt;18, and ≥18 m/s. The incidence density of AMI in 3 groups was calculated. Log-rank test was used to compare the differences of cumulative AMI incidence among 3 groups. The influence of baPWV on new-onset AMI was analyzed by Cox proportional risk model and restricted cubic spline. Results A total of 41,405 subjects were included in the study. During 2.66 (1.07–5.39) years’ follow-up, 150 new-onset AMI cases were observed. The incidence density of AMI in 3 groups was 3.69, 12.79, and 26.65 per 10,000 person-years, respectively. Log-rank test result showed the cumulative AMI incidence increased gradually from the subjects with the lowest baPWV to those with the highest baPWV (P &lt; 0.05). Compared with subjects with baPWV &lt;14 m/s, Cox model showed that hazard ratios (95% confidence interval) of AMI in those with baPWV 14 to &lt;18 m/s and baPWV ≥18 m/s were 1.77 (1.04–3.01) and 1.93 (1.03–3.60) after adjusting for age, sex, and other potential confounding factors, respectively. Restricted cubic spline analysis showed that there was a dose–response relationship between the hazard ratio of AMI and baPWV levels. Conclusions The increased baPWV is a risk factor for new-onset AMI.


2022 ◽  
Vol 7 (1) ◽  
pp. e000830
Author(s):  
Francesca Cappelli ◽  
Carlo Alberto Cutolo ◽  
Sara Olivari ◽  
Valeria Testa ◽  
Daniele Sindaco ◽  
...  

ObjectiveTo compare the two surgical techniques in terms of efficacy, safety, and postoperative management over 36 months of follow-up.MethodsThis retrospective clinical cohort study compared the outcome of trabeculectomy surgery and Xen gel implant in patients having uncontrolled glaucoma. Patients were recruited using the following inclusion criteria: uncontrolled intraocular pressure (IOP) on maximally tolerated medical therapy, healthy conjunctiva freely mobile in the superior sector, open-angle, glaucomatous visual field damage, full follow upfollow-up of at least 36 months. Thirty-four patients were submitted to trabeculectomy and 34 to Xen gel implant. We set the lower limit at 6mmHg mm Hg and the upper limit ≤12 mm Hg for criteria A, upper limit to ≤15 mm Hg for criteria B and upper limit ≤18 mm Hg for criteria C. Criteria for success have been characterizedcharacterised according to whether or not this has been achieved without (complete success) or with IOP -lowering medications (qualified success).ResultsFor all survival curves, trabeculectomy was superior to Xen gel implant. When considering complete success, the log-rank test for criteria A was statistically significant (pp=0.006), marginally significant for criteria B (pp=0.065) and not significant for criteria C (pp=0.23). When qualified success was considered, trabeculectomy was superior to Xen gel for criteria A, B, and C (pp=0.012, pp=0.033 and pp=0.025, respectively). Higher number of post-operative flat chamber and bleb leakage was observed in the trabeculectomy group.ConclusionXen gel implant techniques offer a better safety profile but a lower IOP reduction compared to compared with the gold -standard technique.


2021 ◽  
Vol 12 (3) ◽  
pp. 020-032
Author(s):  
Kshivets Oleg

Methods: We analyzed data of 796 consecutive GCP (age=57.1±9.4 years; tumor size=5.4±3.1 cm) radically operated (R0) and monitored in 1975-2021 (m=556, f=240; distal gastrectomies-G=461, proximal G=165, total G=170, D2 lymph node dissection=551; combined G with resection of 1-7 adjacent organs (pancreas, liver, diaphragm, esophagus, colon transversum, splenectomy, small intestine, kidney, adrenal gland, etc.)=245; D3-4 lymph node dissection=245; only surgery-S=623, adjuvant chemoimmunotherapy-AT=173: 5FU+thymalin/taktivin; T1=237, T2=220, T3=182, T4=157; N0=435, N1=109, N2=252, M0=796; G1=222, G2=164, G3=410; early GC=164, invasive GC=632; Variables selected for 10YS study were input levels of 45 blood parameters, sex, age, TNMG, cell type, tumor size. Survival curves were estimated by the Kaplan-Meier method. Differences in curves between groups of GCP were evaluated using a log-rank test. Multivariate Cox modeling, discriminant analysis, clustering, SEPATH, Monte Carlo, bootstrap and neural networks computing were used to determine any significant dependence. Results: Overall life span (LS) was 2130.8±2304.3 days and cumulative 5-year survival (5YS) reached 58.4%, 10 years – 52.4%, 20 years – 40.4%. 316 GCP lived more than 5 years (LS=4316.1±2292.9 days), 169 GCP – more than 10 years (LS=5919.5±2020 days). 294 GCP died because of GC (LS=640.6±347.1 days). AT significantly improved 10YS (62.3% vs. 50.5%) (P=0.0228 by log-rank test) for GCP. Cox modeling displayed that 10YS of LCP significantly depended on: phase transition (PT) early-invasive GC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, AT, blood cell circuit, prothrombin index, hemorrhage time, residual nitrogen, age, sex, procedure type (P=0.000-0.039). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 10YS and healthy cells/CC (rank=1), PT early-invasive GC (rank=2), PT N0—N12(rank=3), erythrocytes/CC (4), thrombocytes/CC (5), monocytes/CC (6), segmented neutrophils/CC (7), eosinophils/CC (8), leucocytes/CC (9), lymphocytes/CC (10), stick neutrophils/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0). Conclusions: 10-Year survival of GCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) GC characteristics; 9) anthropometric data; 10) surgery type. Optimal diagnosis and treatment strategies for GC are: 1) screening and early detection of GC; 2) availability of experienced abdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunotherapy for GCP with unfavorable prognosis.


2021 ◽  
pp. 1-13
Author(s):  
Elham Kalantari ◽  
Roya Ghods ◽  
Leili Saeednejad Zanjani ◽  
Mandana Rahimi ◽  
Leila Eini ◽  
...  

BACKGROUND: Isoform-specific function of doublecortin-like kinase 1 (DCLK1) has highlighted the key role of the DCLK1-S (short isoform) in the maintenance, progression, and invasion of the tumor. OBJECTIVE: This study was designed to produce an anti-DCLK1-S polyclonal antibody to evaluate DCLK1-S in human colorectal cancer (CRC) specifically. METHODS: The expression pattern and clinical significance of DCLK1-S were assessed in a well-defined tissue microarray (TMA) series of 348 CRC and 51 adjacent normal tissues during a follow-up period of 108 months. RESULTS: Expression of DCLK1-S was significantly higher in CRC samples compared to adjacent normal samples (P< 0.001). Cytoplasmic expression of DCLK1-S was significantly higher in the tumors at the advanced stage of cancer and with poorer differentiation (P< 0.001, P= 0.02). The patients with CRC whose tumors showed higher cytoplasmic expression of DCLK1-S had worse disease-specific survival (DSS) (log-rank test, P= 0.03) and 5-year DSS rates (P= 0.01). Additionally, an improved prognostic value was observed in the patients with CRC with high DCLK1-S expression vs. its moderate expression (HR: 2.70, 95% CI: 0.98–7.38; p= 0.04) by multivariate analysis. CONCLUSIONS: Our findings strongly supported that high cytoplasmic expression of DCLK1-S compared to its moderate expression could be considered an independent prognostic factor influencing DSS.


Author(s):  
Beata Smielak ◽  
Oskar Armata ◽  
Witold Bojar

Abstract Objectives The present study compares the survival rates of 186 conventional and no-prep/minimally invasive porcelain veneers in 35 patients over a mean period of 9 years. Materials and methods The veneers were placed on the incisors, canines, and premolars in 35 patients between January 2009 and December 2010. Fourteen patients received 84 conventional veneers, and 21 patients received 102 no-prep/minimally invasive veneers. The restorations were evaluated at baseline and after every 6 months until June 2019 based on modified United States Public Health Service criteria. The data was analyzed by using Wilcoxon–Breslow–Gehan and Taron–Ware tests. Kaplan–Meier survival and success curves were plotted for two groups of veneers. The results were compared by using the log rank test. A test probability of P < .05 was regarded as significant, while a test probability of P < .01 was considered to be statistically significant. Results The mean survival rate, according to the Kaplan–Meier estimator, was 9.67% for conventional veneers and 100% for the no-prep or minimal prep veneers. A total of ten absolute failures were observed in six patients: eight restoration chipping/fractures, one debonding, and one fracturing of the tooth. Mean success rate time for conventional veneers without absolute or relative failures was 9.32 years, and 10.28 years for no-prep/minimally invasive veneers. Conclusions Over a mean observation period of 9 years, the survival rate of no-prep/minimally invasive veneers exceed that of conventional veneers. Clinical relevance No-prep/minimally invasive veneers appear very effective and should always be considered in certain clinical situations.


2021 ◽  
Vol 12 ◽  
Author(s):  
Carlo Sorrentino ◽  
Luigi D’Antonio ◽  
Cristiano Fieni ◽  
Stefania Livia Ciummo ◽  
Emma Di Carlo

Colorectal cancer (CRC) is one of the most common cancer worldwide, with a growing impact on public health and clinical management. Immunotherapy has shown promise in the treatment of advanced cancers, but needs to be improved for CRC, since only a limited fraction of patients is eligible for treatment, and most of them develop resistance due to progressive immune exhaustion. Here, we identify the transcriptional, molecular, and cellular traits of the immune exhaustion associated with CRC and determine their relationships with the patient’s clinic-pathological profile. Bioinformatic analyses of RNA-sequencing data of 594 CRCs from TCGA PanCancer collection, revealed that, in the wide range of immune exhaustion genes, those coding for PD-L1, LAG3 and T-bet were associated (Cramér’s V=0.3) with MSI/dMMR tumors and with a shorter overall survival (log-rank test: p=0.0004, p=0.0014 and p=0.0043, respectively), whereas high levels of expression of EOMES, TRAF1, PD-L1, FCRL4, BTLA and SIGLEC6 were associated with a shorter overall survival (log-rank test: p=0.0003, p=0.0188, p=0.0004, p=0.0303, p=0.0052 and p=0.0033, respectively), independently from the molecular subtype of CRC. Expression levels of PD-L1, PD-1, LAG3, EOMES, T-bet, and TIGIT were significantly correlated with each other and associated with genes coding for CD4+ and CD8+CD3+ T cell markers and NKp46+CD94+EOMES+T-bet+ cell markers, (OR &gt;1.5, p&lt;0.05), which identify a subset of group 1 innate lymphoid cells, namely conventional (c)NK cells. Expression of TRAF1 and BTLA co-occurred with both T cell markers, CD3γ, CD3δ, CD3ε, CD4, and B cell markers, CD19, CD20 and CD79a (OR &gt;2, p&lt;0.05). Expression of TGFβ1 was associated only with CD4+ and CD8+CD3ε+ T cell markers (odds ratio &gt;2, p&lt;0.05). Expression of PD-L2 and IDO1 was associated (OR &gt;1.5, p&lt;0.05) only with cNK cell markers, whereas expression of FCRL4, SIGLEC2 and SIGLEC6 was associated (OR &gt;2.5; p&lt;0.05) with CD19+CD20+CD79a+ B cell markers. Morphometric examination of immunostained CRC tissue sections, obtained from a validation cohort of 53 CRC patients, substantiated the biostatistical findings, showing that the highest percentage of immune exhaustion gene expressing cells were found in tumors from short-term survivors and that functional exhaustion is not confined to T lymphocytes, but also involves B cells, and cNK cells. This concept was strengthened by CYBERSORTx analysis, which revealed the expression of additional immune exhaustion genes, in particular FOXP1, SIRT1, BATF, NR4A1 and TOX, by subpopulations of T, B and NK cells. This study provides novel insight into the immune exhaustion landscape of CRC and emphasizes the need for a customized multi-targeted therapeutic approach to overcome resistance to current immunotherapy.


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