Post-LASIK dry eye disease: A comprehensive review of management and current treatment options.

Laser-assisted in situ keratomileusis (LASIK) is a unique corneal stromal laser ablation method that uses an excimer laser to reach beneath corneal dome-shaped tissues. In contrast, surface ablation methods, such as photorefractive keratectomy, include removing epithelium and cutting off the Bowman's layer and the stromal tissue of the anterior corneal surface. Dry eye disease (DED) is the most common complication after LASIK. DED is a typical multi-factor disorder of the tear function and ocular surface that occurs when the eyes fail to produce efficient or adequate volumes of tears to moisturize the eyes. DED influences quality of life and visual perception, as symptoms often interfere with daily activities such as reading, writing, or using video display monitors. Generally, DED brings about discomfort, symptoms of visual disturbance, focal or global tear film instability with possible harm to the ocular surface, the increased osmolarity of the tear film, and subacute inflammation of the ocular surface. Almost all patients develop a degree of dryness in the postoperative period. Detection of preoperative DED and committed examination and treatment in the preoperative period, and continuing treatments postoperatively lead to rapid healing, fewer complications, and improved visual outcomes. To improve patient comfort and surgical outcomes, early treatment is required. Therefore, in this study, we aim to comprehensively review studies on the management and current treatment options for post-LASIK DED.

Monoclonal antibodies for the treatment of squamous cell carcinoma: A literature review.

BACKGROUND: Squamous cell carcinoma (SCC) is a relatively common and heterogenous malignancy of different organs, such as the skin, esophagus, and lungs. Although most cases experience good survival with surgical methods, management of advanced types of the disease remains challenging. Several modalities, including different chemotherapy regimens and immunotherapies, have been investigated in this matter, among which Monoclonal antibodies (Mabs) are one of the most promising ones. Since the development of Mabs, they have been widely used to treat different diseases. Mabs have shown significant efficacy with high specificity along with acceptable safety, which makes them a favorable option in cancer therapy. In this article, we aimed to review the different aspects of using Mabs in SCC therapy. RECENT FINDINGS: We found that treating with different Mabs has shown excellent efficacy accompanied by acceptable safety in treating SCC of different organs. Therefore, Mabs are considered great options in the treatment of SCC, especially in advanced cases. Overall, two highly potent types of Mabs in SCC therapy are anti-EGFR Mabs and checkpoint inhibitors, especially Cetuximab, Nimotuzumab, and PD-1 inhibitors. Bevacizumab is also a promising option as adjuvant therapy to other modalities. CONCLUSION: Although some Mabs have shown promising outcomes in SCC therapy, their application as a part of cancer treatment depends on further investigations regarding cost-effectiveness and predictors of response. FDA has approved several Mabs in SCC therapies, and Mabs may have a crucial role in this era in the near future, especially in treating head and neck and esophageal SCC and metastatic lung cancer.

Autophagy orchestrates resistance in hepatocellular carcinoma cells.

Treatment resistance is one of the major barriers for therapeutic strategies in hepatocellular carcinoma (HCC). Many studies have indicated that chemotherapy and radiotherapy induce autophagy machinery (cell protective autophagy) in HCC cells. In addition, many experiments report a remarkable crosstalk between treatment resistance and autophagy pathways. Thus, autophagy could be one of the key factors enabling tumor cells to hinder induced cell death after medical interventions. Therefore, extensive research on the molecular pathways involved in resistance induction and autophagy have been conducted to achieve the desired therapeutic response. The key molecular pathways related to the therapy resistance are TGF-ß, MAPK, NRF2, NF-κB, and non-coding RNAs. In addition, EMT, drug transports, apoptosis evasion, DNA repair, cancer stem cells, and hypoxia could have considerable impact on the hepatoma cell's response to therapies. These mechanisms protect tumor cells against various treatments and many studies have shown that each of them is connected to the molecular pathways of autophagy induction in HCC. Hence, autophagy inhibition may be an effective strategy to improve therapeutic outcome in HCC patients. In this review, we further highlight how autophagy leads to poor response during treatment through a complex molecular network and how it enhances resistance in primary liver cancer. We propose that combinational regimens of approved HCC therapeutic protocols plus autophagy inhibitors may overcome drug resistance in HCC therapy.

The Association between COVID-19 and Reactive Arthritis: A Systematic Review of Case Reports and Case Series.

INTRODUCTION: Reactive arthritis (ReA) is a joint inflammation that follows an infection at a distant site, often in the gastrointestinal or urogenital tract. Since the emergence of COVID-19 in January 2020, several case reports have suggested a relation between reactive arthritis and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), due to the novelty of the disease, most findings were reported in the form of case reports or case series, and a comprehensive overview is still lacking. METHODS: We searched PubMed/Medline and Embase to identify studies addressing the association between ReA and COVID-19. The following terms were used: ("Reactive Arthritis" OR "Post-Infectious Arthritis" OR "Post Infectious Arthritis") AND ("COVID-19" OR "SARS-CoV-2" OR "2019-nCoV"). RESULTS: A total number of 35 reports published up to February 16th, 2022, were included in this study. A wide range of ages was affected (mean 41.0, min 4 max 78), with a higher prevalence of males (61.0%) from 16 countries. The number and location of the affected joints were different in included patients, with a higher prevalence of polyarthritis in 41.5% of all cases. Cutaneous manifestations and visual impairments were found as the most common associated symptoms. Most patients (95.1%) recovered, with a mean recovery time of 24 days. Moreover, arthritis induced by COVID-19 seems to relieve faster than ReA, followed by other infections. CONCLUSION: ReA can be a possible sequel of COVID-19 infection. Since musculoskeletal pain is a frequent symptom of COVID-19, ReA with rapid onset can easily be misdiagnosed. Therefore, clinicians should consider ReA a vital differential diagnosis in patients with post-COVID-19 joint swelling. Additional studies are required for further analysis and to corroborate these findings.

Generalizable machine learning approach for COVID-19 mortality risk prediction using on-admission clinical and laboratory features.

We aimed to propose a mortality risk prediction model using on-admission clinical and laboratory predictors. We used a dataset of confirmed COVID-19 patients admitted to three general hospitals in Tehran. Clinical and laboratory values were gathered on admission. Six different machine learning models and two feature selection methods were used to assess the risk of in-hospital mortality. The proposed model was selected using the area under the receiver operator curve (AUC). Furthermore, a dataset from an additional hospital was used for external validation. 5320 hospitalized COVID-19 patients were enrolled in the study, with a mortality rate of 17.24% (N = 917). Among 82 features, ten laboratories and 27 clinical features were selected by LASSO. All methods showed acceptable performance (AUC > 80%), except for K-nearest neighbor. Our proposed deep neural network on features selected by LASSO showed AUC scores of 83.4% and 82.8% in internal and external validation, respectively. Furthermore, our imputer worked efficiently when two out of ten laboratory parameters were missing (AUC = 81.8%). We worked intimately with healthcare professionals to provide a tool that can solve real-world needs. Our model confirmed the potential of machine learning methods for use in clinical practice as a decision-support system.

Immunotherapeutic approaches in Hepatocellular carcinoma: Building blocks of hope in near future.

Hepatocellular carcinoma (HCC) is the most common type of primary hepatic cancer and is among the major causes of mortality due to cancer. Due to the lack of efficient conventional therapeutic options for this cancer, particularly in advanced cases, novel treatments including immunotherapy have been considered. However, despite the encouraging clinical outcomes after implementing these innovative approaches, such as oncolytic viruses (OVs), adoptive cell therapies (ACT), immune checkpoint blockades (ICBs), and cancer vaccines, several factors have restricted their therapeutic effect. The main concern is the existence of an immunosuppressive tumor microenvironment (TME). Combination of different ICBs or ICBs plus tyrosine kinase inhibitors have shown promising results in overcoming these limiting factors to some extent. Combination of programmed cell death ligand-1 (PD-L1) antibody Atezolizumab and vascular endothelial growth factor (VEGF) antibody Bevacizumab has become the standard of care in the first-line therapy for untestable HCC, approved by regulatory agencies. This paper highlighted a wide overview of the direct and indirect immunotherapeutic strategies proposed for the treatment of HCC patients and the common challenges that have hindered their further clinical applications.

Hepatogenesis and hepatocarcinogenesis: Alignment of the main signaling pathways.

Development is a symphony of cells differentiation in which different signaling pathways are orchestrated at specific times and periods to form mature and functional cells from undifferentiated cells. The similarity of the gene expression profile in malignant and undifferentiated cells is an interesting topic that has been proposed for many years and gave rise to the differentiation-therapy concept, which appears a rational insight and should be reconsidered. Hepatocellular carcinoma (HCC), as the sixth common cancer and the third leading cause of cancer death worldwide, is one of the health-threatening complications in communities where hepatotropic viruses are endemic. Sedentary lifestyle and high intake of calories are other risk factors. HCC is a complex condition in which various dimensions must be addressed, including heterogeneity of cells in the tumor mass, high invasiveness, and underlying diseases that limit the treatment options. Under these restrictions, recognizing, and targeting common signaling pathways during liver development and HCC could expedite to a rational therapeutic approach, reprograming malignant cells to well-differentiated ones in a functional state. Accordingly, in this review, we highlighted the commonalities of signaling pathways in hepatogenesis and hepatocarcinogenesis, and comprised an update on the current status of targeting these pathways in laboratory studies and clinical trials.

Clinical and laboratory findings following transplantation of allogeneic adipose-derived mesenchymal stromal cells in knee osteoarthritis, a brief report.

BACKGROUND: Mesenchymal stromal cells (MSCs) injection has been proposed as an innovative treatment for knee osteoarthritis (KOA). Since, allogeneic MSCs can be available as off-the-shelf products, they are preferable in regenerative medicine. Among different sources for MSCs, adipose-derived MSCs (AD-MSCs) appear to be more available. METHODS: Three patients with KOA were enrolled in this study. A total number of 100 × 106 AD-MSCs was injected intra-articularly, per affected knee. They were followed up for 6 months by the assessment of clinical outcomes, magnetic resonance imaging (MRI), and serum inflammatory biomarkers. RESULTS: The primary outcome of this study was safety and feasibility of allogeneic AD-MSCs injection during the 6 months follow-up. Fortunately, no serious adverse events (SAEs) were reported. Assessment of secondary outcomes of visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and knee osteoarthritis outcome score (KOOS) indicated improvement in all patients. Comparison between baseline and endpoint findings of MRI demonstrated a slight improvement in two patients. In addition, decrease in serum cartilage oligomeric matrix protein (COMP) and hyaluronic acid (HA) indicated the possibility of reduced cartilage degeneration. Moreover, quantification of serum interleukin-10 (IL-10) and interleukin-6 (IL-6) levels indicated that the host immune system immunomodulated after infusion of AD-MSCs. CONCLUSION: Intra-articular injection of AD-MSCs is safe and could be effective in cartilage regeneration in KOA. Preliminary assessment after six-month follow-up suggests the potential efficacy of this intervention which would need to be confirmed in randomized controlled trials on a larger population. TRIAL REGISTRATION: This study was registered in the Iranian registry of clinical trials (https://en.irct.ir/trial/46) in 24 April 2018 with identifier IRCT20080728001031N23.

PSC associated inflammatory bowel disease: a distinct entity.

INTRODUCTION: Primary sclerosing cholangitis (PSC) is a rare, chronic, and progressive cholestatic disease involving intra- and/or extrahepatic bile ducts. PSC in many patients results in end-stage liver diseases. Nearly 60% of the PSC patients suffer from concomitant inflammatory bowel diseases (IBDs). Classically, IBDs are divided into two principle types: Crohn's disease (CD) and ulcerative colitis (UC). However, with growing knowledge, PSC-associated IBD (PSC-IBD) seems to be a rather distinct entity with specific genetics, clinical, and microbiota characteristics. AREAS COVERED: In this article, we aim to review the unique characteristics of PSC-IBD from clinical, genetic, and microbiota point of view. EXPERT OPINION: PSC-IBD's unique characteristics contribute to the notion that it could be a distinct entity. Acknowledgment of PSC-IBD as a novel entity necessitates designing new clinical guidelines for diagnosis and developing novel therapies.

Ameliorating effects of curcumin-loaded superparamagnetic iron oxide nanoparticles (SPIONs) on the mouse testis exposed to the transient hyperthermia: A molecular and stereological study.

BACKGROUND: Testicular hyperthermia can have negative effects on male fertility. Despite reported therapeutic benefits of curcumin, several factors often limit its application such as low water solubility and instable structure. Curcumin-loaded superparamagnetic iron oxide nanoparticles (SPIONs) were designed to solve its limitation of use. In the present study, we evaluated the effect of curcumin-loaded SPIONs on transient testicular hyperthermia in mouse. MATERIALS AND METHOD: A total of 18 adult male NMRI mice were divided into three groups (n = 6): I. Controls (Cont), II. Scrotal hyperthermia (Hyp), III. Scrotal hyperthermia + curcumin-loaded iron particles (240 µL) (Hyp + Cur). After seventy days, the animals were sacrificed and used for further molecular and stereological evaluations. RESULTS: Sperm count, motility and viability significantly decreased in group hyp as compared to cont group. Furthermore, Sperm DNA fragmentation and cell apoptosis in testes increased remarkably in group hyp, compared with group cont. Stereological study showed a reduction in number of spermatogenic and Leydig cells, as well as reduced weight and volume of testes in hyp group. Degenerative appearance of testes exposed to hyperthermia was also observed. In addition, higher mRNA expression of inflammatory cytokines (IL1-α, IL6, and TNF-α) was detected in group hyp compared to cont group. However, curcumin-loaded SPIONs alleviated all of the pathologic changes in the Hyp + Cur group compared to the hyp group. CONCLUSION: Here, we used nanoparticle form of curcumin in testicular hyperthermia model and showed its ameliorating effects on testes damages caused by heat stress, which can be an appropriate method to overcome the problems that limit curcumin application in cases with increased intra testicular temperature.