Outcomes of Y90 Radioembolization for Hepatocellular Carcinoma in Patients Previously Treated with Transarterial Embolization.

The aim of this study was to evaluate outcomes of transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) in patients previously treated with transarterial embolization (TAE). In this retrospective study, all HCC patients who received TARE from 1/2012 to 12/2022 for treatment of residual or recurrent disease after TAE were identified. Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate Cox regression was performed to determine significant predictors of OS after TARE. Twenty-one patients (median age 73.4 years, 18 male, 3 female) were included. Median dose to the perfused liver volume was 121 Gy (112-444, range), and 18/21 (85.7%) patients received 112-140 Gy. Median OS from time of HCC diagnosis was 32.9 months (19.4-61.4, 95% CI). Median OS after first TAE was 29.3 months (15.3-58.9, 95% CI). Median OS after first TARE was 10.6 months (6.8-27.0, 95% CI). ECOG performance status of 0 (p = 0.038), index tumor diameter < 4 cm (p = 0.022), and hepatic tumor burden < 25% (p = 0.018) were significant predictors of longer OS after TARE. TARE may provide a survival benefit for appropriately selected patients with HCC who have been previously treated with TAE.

Immune Effects of Intra-Arterial Liver-Directed Therapies.

Image-guided intra-arterial locoregional therapies (LRTs) such as transarterial embolization, transarterial chemoembolization, and transarterial radioembolization exhibit effects on the immune system. Understanding the humoral (cytokine, chemokine, and growth factor) and cellular (T cell, neutrophil, dendritic cell, and macrophage) mechanisms underlying the immune effects of LRT is crucial to designing rational and effective combinations of immunotherapy and interventional radiology procedures. This article aims to review the immune effects of intra-arterial LRTs and provide insight into strategies to combine LRTs with systemic immunotherapy.

Evaluation of Long Non-coding RNA (LncRNA) in the Pathogenesis of Chemotherapy Resistance in Cervical Cancer: Diagnostic and Prognostic Approach.

Cervical cancer (CC), caused by human papillomavirus (HPV), is a leading cause of female malignancies worldwide. Therefore, understanding the underlying mechanisms of CC development and identifying novel therapeutic targets are significantly important. Cisplatin resistance is a significant challenge in the management of CC. Recent studies highlighted the critical role of long non-coding RNAs (lncRNAs) in modulation of cisplatin resistance. This comprehensive review aims to collect the current understanding roles of lncRNAs and their involvement in cisplatin resistance in CC by highlighting key processes of cancer progression, including apoptosis, proliferation, angiogenesis and epithelial-to-mesenchymal transition (EMT). We discussed the role of lncRNA in CC resistance to cisplatin through molecular pathways and examined gene expression changes. We also discussed treatment strategies and factors that reduce CC resistance to cisplatin by targeting them.

Anti-Glycolytic Drugs in the Treatment of Hepatocellular Carcinoma: Systemic and Locoregional Options.

Hepatocellular cancer (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death. Locoregional therapies, including transarterial embolization (TAE: bland embolization), chemoembolization (TACE), and radioembolization, have demonstrated survival benefits when treating patients with unresectable HCC. TAE and TACE occlude the tumor's arterial supply, causing hypoxia and nutritional deprivation and ultimately resulting in tumor necrosis. Embolization blocks the aerobic metabolic pathway. However, tumors, including HCC, use the "Warburg effect" and survive hypoxia from embolization. An adaptation to hypoxia through the Warburg effect, which was first described in 1956, is when the cancer cells switch to glycolysis even in the presence of oxygen. Hence, this is also known as aerobic glycolysis. In this article, the adaptation mechanisms of HCC, including glycolysis, are discussed, and anti-glycolytic treatments, including systemic and locoregional options that have been previously reported or have the potential to be utilized in the treatment of HCC, are reviewed.

N-acetylcysteine as adjuvant therapy for hospitalized Covid-19 patients: A single-center prospective cohort study.

Background: Whilst over two years have passed since the COVID-19 pandemic's emergence, the proper management of the disease remains challenging. N-acetylcysteine (NAC) as a potentially effective therapeutic option has been suggested by studies, while the exact clinical role of this agent is yet to be evaluated. Methods: This prospective case-control study was conducted in a major referral respiratory center in Tehran, Iran. We enrolled 217 patients treated with an intravenous daily dose of 1500 mg NAC as a case group; and 245 control patients who did not receive NAC. Two groups were matched based on other treatments, socio-demographics, medical history, and comorbidities. Results: After ten days of adjuvant therapy with NAC, patients in the NAC group and control group had median room-air SpO2 of 91% and 88%, respectively (P=0.02). Also, the SpO2 to FiO2 ratio had a median of 463 and 421 in the case and control groups, respectively (P=0.01). Furthermore, the case group's hospitalization period was three days shorter (P=0.002). Further, cough, dyspnea, and decreased appetite were reported to have a significantly lower incidence in the case group (P=0.03, 0.001, 0.008). Conclusion: We showed that a daily intravenous dose of NAC in hospitalized COVID-19 patients could shorten the hospital stay and improve some clinical symptoms; however, it does not remarkably improve the risk of ICU admission and the 28 days in-hospital mortality rate.

Factors affecting outcomes of Yttrium-90 radioembolization in heavily pretreated patients with intrahepatic cholangiocarcinoma.

PURPOSE: Transarterial radioembolization (TARE) is a liver-directed treatment for unresectable intrahepatic cholangiocarcinoma (ICC). The aim of this study is to evaluate factors affecting outcomes of TARE in heavily pretreated ICC patients. METHODS: We evaluated pretreated ICC patients who received TARE from January 2013 to December 2021. Prior treatments included systemic therapy, hepatic resection, and liver-directed therapies, including hepatic arterial infusion chemotherapy, external beam radiation, transarterial embolization, and thermal ablation. Patients were classified based on history of hepatic resection and genomic status based on next-generation sequencing (NGS). The primary endpoint was overall survival (OS) after TARE. RESULTS: Fourteen patients with median age 66.1 years (range, 52.4-87.5), 11 females and 3 males, were included. Prior therapies included systemic in 13/14 patients (93%), liver resection in 6/14 (43%), and liver-directed therapy in 6/14 (43%). Median OS was 11.9 months (range, 2.8-81.0). Resected patients had significantly longer median OS compared to unresected patients (16.6 versus 7.9 months; p = 0.038). Prior liver-directed therapy (p = 0.043), largest tumor diameter > 4 cm (p = 0.014), and > 2 hepatic segments involvement (p = 0.001) were associated with worse OS. Nine patients underwent NGS; 3/9 (33.3%) and had a high-risk gene signature (HRGS), defined as alterations in TP53, KRAS, or CDKN2A. Patients with a HRGS had worse median OS (10.0 versus 17.8 months; p = 0.024). CONCLUSIONS: TARE may be used as salvage therapy in heavily treated ICC patients. Presence of a HRGS may predict worse OS after TARE. Further investigation with more patients is recommended to validate these results.

Enhanced sciatic nerve regeneration with fibrin scaffold containing human endometrial stem cells and insulin encapsulated chitosan particles: An in vivo study.

BACKGROUND: Based on recent advances in tissue engineering and stem cell therapy in nervous system diseases treatments, this study aimed to investigate sciatic nerve regeneration using human endometrial stem cells (hEnSCs) encapsulated fibrin gel containing chitosan nanoparticle loaded by insulin (Ins-CPs). Stem cells and also Insulin (Ins), which is a strong signaling molecule in peripheral nerve regeneration, play an important role in neural tissue engineering. METHODS: The fibrin hydrogel scaffold containing insulin loaded chitosan particles was synthesized and characterized. Release profiles of insulin from hydrogel was determined through UV-visible spectroscopy. Also, human endometrial stem cells encapsulated in hydrogel and its cell biocompatibility were assigned. Furthermore, the sciatic nerve crush injury was carried out and prepared fibrin gel was injected at the crush injury site by an 18-gage needle. Eight and twelve weeks later, the recovery of motor and sensory function and histopathological evaluation were assessed. RESULTS: The in vitro experiments showed that the insulin can promote hEnSCs proliferation within a certain concentration range. Animals' treatment confirmed that developed fibrin gel containing Ins-CPs and hEnSCs significantly improves motor function and sensory recovery. Hematoxylin and Eosin (H&E) images provided from cross-sectional and, longitudinal-sections of the harvested regenerative nerve showed that regenerative nerve fibers had been formed and accompanied with new blood vessels in the fibrin/insulin/hEnSCs group. CONCLUSION: Our results demonstrated that the prepared hydrogel scaffolds containing insulin nanoparticles and hEnSCs could be considered as a potential biomaterial aimed at regeneration of sciatic nerves.

Recent approaches to mRNA vaccine delivery by lipid-based vectors prepared by continuous-flow microfluidic devices.

Advancements in nanotechnology have resulted in the introduction of several nonviral delivery vectors for the nontoxic, efficient delivery of encapsulated mRNA-based vaccines. Lipid- and polymer-based nanoparticles (NP) have proven to be the most potent delivery systems, providing increased delivery efficiency and protection of mRNA molecules from degradation. Here, the authors provide an overview of the recent studies carried out using lipid NPs and their functionalized forms, polymeric and lipid-polymer hybrid nanocarriers utilized mainly for the encapsulation of mRNAs for gene and immune therapeutic applications. A microfluidic system as a prevalent methodology for the preparation of NPs with continuous flow enables NP size tuning, rapid mixing and production reproducibility. Continuous-flow microfluidic devices for lipid and polymeric encapsulated RNA NP production are specifically reviewed.

Benefit of Hemoadsorption Therapy in Patients Suffering Sepsis-Associated Acute Kidney Injury: A Case Series.

INTRODUCTION: Sepsis is defined as life-threatening organ dysfunction in result of the host's dysregulated response to infection and septic shock. Sepsis-associated kidney injury is usually defined as concurrent presence of acute kidney injury (AKI) and sepsis without other significant causative factors. METHOD: The current retrospective study was conducted to elucidate beneficial and side effects of CytoSorb®. A total of 17 patients were primarily treated with continuous renal replacement therapy in combination with CytoSorb. The demand for norepinephrine, mean arterial pressure, lactate, and procalcitonin (PCT) levels, as well as ICU length of stay, was measured. RESULT: The blood lactate levels decreased by 32.30% when comparing mean levels before and after treatment. All patients who survived (n = 14) had reduction in vasopressor demand to 68.96% of their initial dose before the start of treatment. Hospital survival was greater in patients who initially had higher vasopressor demand compared to their nonsurviving counterparts, but in whom vasopressor dosages were reduced significantly during their treatments. Mortality as predicted by APACHE II score in the overall patient population was 79.9%, whereas, the observed ICU mortality was 31%. The baseline PCT levels on patients received 1, 2, and 3 CytoSorbs were 27.08 ± 5.81 ng/mL, 13.28 ± 2.62 ng/mL, and 21.03 ± 6.56 ng/mL, respectively. Observed PCT levels at 24 h after the last treatment on patients received 1, 2, and 3 CytoSorb were 31.55 ± 15.70 ng/mL, 5.61 ± 1.77 ng/mL, and 8.11 ± 3.62 ng/mL, respectively. CONCLUSION: In conclusion, it seems that applying the CytoSorb in combination with CRRT in ICU septic patients with AKI, is related to a significant decrease in mortality, if the integrity and continuity of the treatment be kept, as much as possible. This study presented an effectively positive outcome with cytokine adsorber treatment as an adjuvant along with standard treatment in a high-risk mortality case of septic shock with organ failure.

The Clinical Outcome of Laparoscopic Surgery for Endometriosis on Pain, Ovarian Reserve, and Cancer Antigen 125 (CA-125): A Cohort Study.

BACKGROUND: Endometriosis is an important cause of chronic pain and infertility. Surgery is considered the gold standard for diagnosis and treatment. In this study, we aim to describe the clinical outcomes of women who undergo laparoscopic surgery for endometriosis. MATERIALS AND METHODS: In this cohort study, a total of 174 women who referred to Farmaniyeh Hospital, Tehran, Iran from August 2015 to December 2017 with surgical diagnoses of endometriosis stages III and IV enrolled. The participants' demographic, gynaecological, and clinical characteristics were recorded and they were asked to use a numeric rating scale (NRS) to record their severity of pain before and three months after surgery. Blood samples were also taken from the patients before and three months after surgery for measurement of serum levels of anti-Müllerian hormone (AMH) and cancer antigen 125 (CA-125). Data were analysed using SPSS version 21. RESULTS: The patients had a mean age of 34.86 ± 6.47 years, 60.9% were married, and 49.4% were housewives. The primary indication for surgery was pain (68.4%), followed by both pain and infertility in the remainder of patients. Types of endometriotic lesions included endometrioma (19%), deep infiltrating endometriosis (DIE, 3.4%), and both endometrioma and DIE (77.6%). There was a reduction in pain from 6.79 ± 2.19 before surgery to 1.48 ± 1.68 after surgery; serum AMH levels reduced from 2.80 ± 1.86 ng/mL to 1.76 ± 1.40 ng/mL and CA125 reduced from 257.06 ± 220.25 U/mL to 23.27 ± 23.25 U/mL (all P<0.001). Of the 21.2% who experienced recurrence, 13.5% underwent additional surgery. The total additional surgery rate was 2.8%. Of the 55 patients with infertility, 78.1% became pregnant after surgery, 54.5% of which was spontaneous. CONCLUSION: Surgical treatment of endometriosis had a favourable effect on the patients' pain and inflammation and resolved the patients' infertility with a minimal need for additional surgery.

Prevalence and Clinical Outcomes of Vitamin D Deficiency in COVID-19 Hospitalized Patients: A Retrospective Single-Center Analysis.

Vitamin D attenuates inflammatory responses to viral respiratory infections. Hence, vitamin D deficiency may be a highly significant prognostic factor for severity and mortality in COVID-19 patients. To evaluate the complications and mortality in different vitamin D status groups in COVID-19 hospitalized patients, we conducted this retrospective study on 646 laboratory-confirmed COVID-19 patients who were hospitalized in Shahid Modarres Hospital, Tehran, Iran from 16th March 2020 until 25th February 2021. Overall, patients with vitamin D deficiency, insufficiency and sufficiency were 16.9%, 43.6% and 39.5%, respectively. The presence of comorbidity, length of hospitalization, ICU admission, and invasive mechanical ventilation requirement and overall complications were significantly more in patients with vitamin D deficiency (p-value < 0.001). 46.8% (51/109) of vitamin D deficient patients died due to the disease, whilst the mortality rate among insufficient and sufficient vitamin D groups was 29.4% (83/282) and 5.5% (14/255), respectively. In univariate analysis, age > 60 years (odds ratio (OR) = 6.1), presence of comorbidity (OR = 10.7), insufficient vitamin D status (OR = 7.2), and deficient vitamin D status (OR = 15.1) were associated with increase in COVID-19 mortality (p-value < 0.001). Finally, the multivariate analysis adjusted for age, sex, and comorbidities indicated vitamin D deficiency as an independent risk factor for mortality (OR = 3.3, p-value = 0.002). Vitamin D deficiency is a strong risk factor for mortality and severity of SARS-CoV-2 infection. Vitamin D supplementation may be able to prevent or improve the prognosis of COVID-19 during this pandemic.