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Αλέξανδρος Γ. Σφακιανάκης

Thursday, October 28, 2021

Pembrolizumab-induced Remission After Failure of Axicabtagene Ciloleucel: Case Report and Literature Review

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In Vivo. 2021 Nov-Dec;35(6):3401-3406. doi: 10.21873/invivo.12639.

ABSTRACT

BACKGROUND: Failure after CD19-directed chimeric antigen receptor (CAR) T-cell therapy for patients with large B-cell B non-Hodgkin lymphoma, especially when it happens early, is an emerging clinical problem. There are no specific recommendations and therefore treatment of these patients remains empiricaI. Immune checkpoint inhibitors are becoming a therapeutic option for these patients.

CASE REPORT: We present a case of a primary mediastinal large B-cell lymphoma who experienced relapse 3.5 months after axicabtagene-ciloleucel therapy and received pembrolizumab. After four cycles of pembrolizumab, complete metabolic response was confirmed. Treatment was discontinued after the sixth cycle due to immune checkpoint inhibitor-related pneumonitis. The disease remains in remission 8 months after the last pembrolizumab dose. We propose mechanisms of action and optimal duration of pembrolizumab treatment in this setting. Finally, we review the existing literature on the sequential administration of CD19-directed CAR T-cell therapy and immune checkpoint inhibitors.

CONCLUSION: Immune checkpoint inhibitors are a promising treatment option for patients after failure of CD19-directed CAR-T cell therapy.

PMID:34697175 | DOI:10.21873/invivo.12639

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Quality of Life in Swiss Patients With Spongiform Venous Malformations

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In Vivo. 2021 Nov-Dec;35(6):3527-3535. doi: 10.21873/invivo.12655.

ABSTRACT

BACKGROUND/AIM: Spongiform venous malformations (sVMs) get symptomatic in >90% of cases during a person's lifetime. Misdiagnosis is still common and treatment often incomplete, making this disease a lifelong issue for patients with a relevant impact on their quality of life.

PATIENTS AND METHODS: Medical records and imaging studies of patients with VMs from April 2002 to January 2017 were reviewed for confirmation of diagnosis and classification of the VMs. Only sVMs were included. Subjective data were obtained from the survey related to indication, response, and complications. We analyzed the frequency of correct diagnosis and Quality of Life by an SF12-based questionnaire for sVM-related issues in Swiss patients.

RESULTS: A total of 80 patients were included in the study. Forty-six (58%) patients were females. Patients were 11.6-77 years old wi th a median age of 28.1 years. The correct diagnosis according to the ISSVA-classification after having been seen at our Institution was 87%. Thirty-one (39%) patients responded to the survey. Sixteen (51%) were female. Twenty-eight (90%) patients felt that their sVM-related state of health improved within a year. Twelve (39%) patients reported that they could not work as good as normal because of slight to modest impairment by the sVM, while 19 (61%) patients were unimpaired. Mental impairment was found in 8 (26%) patients, while 23 (74%) patients felt no impairment. Eight (26%) patients reported that they were impaired within social contacts due to their sVM. Only 9 (29%) patients reported that venous malformation was diagnosed around birth. Twenty-three (74%) patients received a wrong diagnosis. Patients that were treated, reported close to complete relief of symptoms in 26% (8 patients) while also 26% (8 patients) reported no change of symptoms after therapy.

CONCLUSION: S wiss sVM patients also suffer from misdiagnosis and late diagnosis. They are impacted in their daily life by their disease.

PMID:34697191 | DOI:10.21873/invivo.12655

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Efficacy of Intravenous Use of Lidocaine in Postoperative Pain Management After Laparoscopic Colorectal Surgery: A Meta-analysis and Meta-regression of RCTs

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In Vivo. 2021 Nov-Dec;35(6):3413-3421. doi: 10.21873/invivo.12641.

ABSTRACT

BACKGROUND/AIM: Current literature reports regarding the effect of lidocaine in laparoscopic colectomies are still inconclusive. The purpose of this study was to review the current literature and estimate the overall effect of intravenous lidocaine administration in postoperative recovery of patients submitted to laparoscopic colectomies.

MATERIALS AND METHODS: This study was completed based on the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. A systematic screening using scholar databases was performed (Medline, Scopus, Web of Science, CENTRAL).

RESULTS: In total, 8 studies and 407 patients were included in this meta-analysis. Introduction of intravenous lidocaine in the perioperative analgesia scheme did not improve hospitalization duration (p=0.23), morphine consumption (p=0.96), perioperative bowel function (first flatus p=0.40, first bowel opened p=0.13, first diet p=0.16), or the overall complication rates (p=0.42). Overall, high heterogeneity levels were identified.

CONCLUSION: Current evidence indicates that lidocaine does not improve rehabilitation after laparoscopic colectomies.

PMID:34697177 | DOI:10.21873/invivo.12641

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Hemodynamic Alteration in the Liver in Acute Hepatitis: A Quantitative Evaluation Using Computed Tomographic Perfusion

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In Vivo. 2021 Nov-Dec;35(6):3537-3545. doi: 10.21873/invivo.12656.

ABSTRACT

BACKGROUND/AIM: We aimed to elucidate the hemodynamic alterations in the liver of patients with acute hepatitis (AH) using computed tomography perfusion imaging.

PATIENTS AND METHODS: For 14 patients with AH and nine patients with no disease (ND group), we compared the mean arterial blood flow (AF), portal blood flow (PF) and perfusion index (%) [PI=AF/(AF+PF) ×100] of the right and left liver lobes and investigated their relationship with clinical factors.

RESULTS: The mean PI of the right lobe in the AH group (30.5±10.0%) was significantly higher than that in the ND group (20.8±9.7%) (p=0.031). For all patients of the AH and ND groups, the PI of the right lobe was increased as the prothrombin time decreased (R=-0.56, p=0.006) and as the prothrombin time-international normalized ratio increased (R=0.48, p=0.02).

CONCLUSION: The PI of the r ight liver lobe may increase in AH and may be a predictive parameter for the severity of hepatic failure.

PMID:34697192 | DOI:10.21873/invivo.12656

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Comparison of Three Assays for Total and Free PSA Using Hybritech and WHO Calibrations

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In Vivo. 2021 Nov-Dec;35(6):3431-3439. doi: 10.21873/invivo.12643.

ABSTRACT

BACKGROUND/AIM: Lack of interchangeability between prostate-specific antigen (PSA) assays could have a clinical impact. We compared PSA assays from different manufacturers and calibrations.

PATIENTS AND METHODS: A total of 233 men who underwent prostate biopsy (PSA: 2-10 ng/ml; Beckman Coulter Access® Hybritech® as reference) were enrolled. Total (tPSA) and free PSA (fPSA) were also measured using the Roche cobas® and the Abbott Architect® methods.

RESULTS: Roche tPSA values were ≈1% higher than Beckman, while Abbott values were ≈5% lower. Roche had the highest diagnostic sensitivity (92%) compared to Beckman Coulter (87%) and Abbott (85%). Roche fPSA was ≈3% lower and Abbott ≈17% higher than that of Beckman. For the percentage of fPSA, Roche had the highest sensitivity (98%).

CONCLUSION: Roche cobas® and Beckman Coulter Access® Hybritech® tPSA were almost interchangeable. While the agreement was acceptable for tPSA, this did not happen with fPSA and greater efforts for harmonization are required.

PMID:34697179 | DOI:10.21873/invivo.12643

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Radiotherapy Increases the Incidence of Herpes Zoster in Oral Cavity Cancer Patients - a National Population-based Cohort Study

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In Vivo. 2021 Nov-Dec;35(6):3547-3553. doi: 10.21873/invivo.12657.

ABSTRACT

BACKGROUND/AIM: Oral cavity cancer is a major health problem worldwide. The herpes zoster vaccine is an effective method to protect against herpes zoster infection. In this study we aimed to determine the relationship between herpes zoster and oral cavity cancer.

PATIENTS AND METHODS: The Longitudinal Generation Tracking Database in Taiwan was used to select oral and non-oral cavity cancer patients. The primary endpoint was herpes zoster.

RESULTS: We included 3131 oral cavity cancer patients and 3131 non-oral cavity cancer patients. Patients with oral cavity cancer [adjusted hazard ratio (HR)=1.66, 95% confidence interval (CI)=1.27-2.16] had a significantly higher risk of herpes zoster compared to the control group. The oral cavity patients who received radiotherapy (adjusted HR=1.79, 95%CI=1.12-2.86) had a significantly higher risk of herpes zoster compared to the oral cavity patients who did not receive radiotherapy.

CONCLUSION: Radiotherapy increases the incidence of herpes zoster infection in oral cavity cancer patients.

PMID:34697193 | DOI:10.21873/invivo.12657

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Embryonic Cell-free DNA in Spent Culture Medium: A Non-invasive Tool for Aneuploidy Screening of the Corresponding Embryos

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In Vivo. 2021 Nov-Dec;35(6):3449-3457. doi: 10.21873/invivo.12645.

ABSTRACT

BACKGROUND/AIM: Preimplantation genetic testing (PGT) for chromosomal screening, based on embryo biopsy, has significant limitations. Cell-free DNA (cf-DNA) has been detected in spent culture medium (SCM), opening new horizons for the development of non-invasive PGT (ni-PGT). In this study, we evaluated the diagnostic performance of ni-PGT for aneuploidy (niPGT-A), comparing the results of trophectoderm biopsies (TE) and respective SCM from individually cultured embryos via Next Generation Sequencing (NGS).

MATERIALS AND METHODS: Forty fresh embryos were analyzed. TE and SCM from blastocysts were collected and analyzed.

RESULTS: We detected cfDNA in 100% of samples tested. The overall concordance rate between the ni-PGT-A and PGT-A was 27/33 (81.8%). The full concordance rate was 21/33 (63.6%). The aneuploidy agreement was 91.66%, and the euploidy a greement was 76.19%.

CONCLUSION: We found a good accordance between TE and SCM analysis, suggesting that niPGT-A could be a reliable alternative for chromosomal abnormalities assessment of in vitro cultured embryos.

PMID:34697181 | DOI:10.21873/invivo.12645

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Low Preoperative Albumin-to-Globulin Ratio Is a Marker of Poor Prognosis in Patients With Esophageal Cancer

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In Vivo. 2021 Nov-Dec;35(6):3555-3561. doi: 10.21873/invivo.12658.

ABSTRACT

AIM: Recent studies have reported that the albumin-to-globulin ratio (AGR) may be a useful inflammatory-nutritional biomarker to predict postoperative complications and poor prognosis in various types of patients with cancer. However, its prognostic value in patients with esophageal cancer is still unclear. We aimed to examine the utility of the AGR for predicting the short- and long-term outcomes in patients with esophageal cancer who underwent curative resection.

PATIENTS AND METHODS: This was a retrospective cohort analysis reviewing the medical records of consecutive patients who underwent esophagectomy for clinical stage I to III esophageal cancer at Yokohama City University. A total of 105 patients were identified between 2005 and 2018. The overall survival (OS), recurrence-free survival (RFS), and postoperative complication rates were compared betw een patients with high AGR (>1.48) and those with low AGR (≤1.48) group.

RESULTS: A total of 57 and 48 patients were classified into the high and low AGR groups, respectively. There was no significant difference between the two groups in the rate of overall postoperative complications of more than Clavien-Dindo grade 3 (50.9% vs. 54.2%, p=0.85). The long-term findings showed that 5-year OS and RFS rates were significantly better for the group with a high AGR (67.2% vs. 33.8%, p<0.001 and 51.6% vs. 28.5%, p=0.003, respectively).

CONCLUSION: This study suggests that a low preoperative AGR is a risk factor for poor RFS and OS in patients who are planning to undergo curative surgery for esophageal cancer. AGR may be a useful biomarker for establishing treatment strategies to improve patients' survival.

PMID:34697194 | DOI:10.21873/invivo.12658

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Herpes Zoster Vaccination Reduces Risk of Dementia

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In Vivo. 2021 Nov-Dec;35(6):3271-3275. doi: 10.21873/invivo.12622.

ABSTRACT

Background/Αim: The relationship of herpes viruses and herpes zoster (HZ) with dementia and Alzheimer's disease is controversial. This study evaluated the relationship between HZ vaccination and cognitive impairment.

PATIENTS AND METHODS: We used data from The Behavioral Risk Factor Surveillance System (BRFSS) to evaluate the relationship between HZ vaccination and cognitive impairment.

RESULTS: Using BRFSS 2017 data, we assessed HZ vaccination status in 275 subjects whose social activities were hampered by disorientation or memory loss. 61.6% of vaccinated subjects (n=61) and 46.6% of unvaccinated subjects (n=82) never had social activities hampered by disorientation or memory loss. The result is significant (p=0.025, two- sided Fisher exact test). The results of multivariate linear regression analysis, considering social activities hampered by di sorientation or memory loss as a dependent variable, and vaccination (yes or no), sex, and education level as independent variables, showed that the effect of vaccination--reducing risk of social activities hampered by disorientation or memory loss--was significant (p=0.03).

CONCLUSION: Our finding that HZ vaccination reduces the risk of dementia is consistent with the link between viruses and AD. Herpes viruses-induced reactivation of embryologic pathways silenced at birth could be one of the pathologic processes in Alzheimer's disease.

PMID:34697158 | DOI:10.21873/invivo.12622

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Impact of C-reactive Protein Flare Response in Patients With Advanced Urothelial Carcinoma Who Received Pembrolizumab

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In Vivo. 2021 Nov-Dec;35(6):3563-3568. doi: 10.21873/invivo.12659.

ABSTRACT

BACKGROUND/AIM: To clarify the clinical significance of the temporary elevated C-reactive protein (CRP) levels followed by a decrease below baseline (CRP flare response) after administration of pembrolizumab to patients with advanced urothelial carcinoma (UC).

PATIENTS AND METHODS: We retrospectively reviewed 31 patients with advanced UC who received pembrolizumab. Patients were categorized into 3 groups (flare-responder, responder, non-responder) according to early CRP kinetics. Intergroup tumor response and survivals were compared.

RESULTS: Objective response rates of flare-responder, responder, and non-responder groups were 75%, 80%, and 26%, respectively. Median overall survival was not reached in flare-responder and responder groups, and was 10.2 months in the non-responder group (p=0.03). Furthermore, the flare-responder group did not reach me dian progression-free survival, and for the responder and non-responder groups it was 15.2 and 2.8 months, respectively (p=0.03).

CONCLUSION: CRP flare response might be a promising biomarker in patients with advanced UC who received pembrolizumab.

PMID:34697195 | DOI:10.21873/invivo.12659

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Combination of the CD8+:B-cell and Neutrophil-to-Lymphocyte Ratio as a Novel Prediction Model for Intubation Need and Disease Severity in COVID-19 Patients

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In Vivo. 2021 Nov-Dec;35(6):3305-3313. doi: 10.21873/invivo.12626.

ABSTRACT

BACKGROUND: The study provides a novel prediction model for COVID-19 progression and outcome by the combination of the CD8+: B-cells ratio with neutrophil-to-lymphocyte ratio (NLR).

PATIENTS AND METHODS: Immune phenotyping was performed in 120 COVID-19 patients.

RESULTS: A decrease in CD8+:B-cell (p<0.0001) and in lymphocyte-to-CRP (LCR) ratio (p<0.0001) was observed in intubated patients versus non-intubated with an increase for CD4+:CD8+ (p<0.01), NLR (p<0.0001) and CRP: Albumin (p<0.001). Receiving operating curve (ROC) analysis predicting requirement for mechanical ventilation revealed the highest AUC for CD8+:B-cells, (AUC=0.795, p<0.001) versus NLR (AUC=0.783, p<0.001), LCR (AUC=0.779, p<0.001), Albumin:CRP (AUC=0.750, p<0.001) and CD4+:CD8+ (AUC=0.779, p<0.001). Combination of the CD8+: B-cell ratio with the NLR increased the AUC (AUC=0.845, p<0.001). The combined ratios correlated with outcome defined as duration of hospital (r=0.435, p<0.001) or ICU stay (r=0.596, p<0.001).

CONCLUSION: Combination of the CD8+: B-cell ratio and NLR serves as a useful prognostic tool for COVID-19 patient progression.

PMID:34697162 | DOI:10.21873/invivo.12626

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