The role of long noncoding RNAs in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with a poor prognosis leading to death. The diagnosis and treatment of ALS are inherently challenging due to its complex pathomechanism. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides involved in different cellular processes, incisively gene expression. In recent years, more studies have been conducted on lncRNA classes and interference in different disease pathologies, showing their promising contribution to diagnosing and treating neurodegenerative diseases. In this review, we discussed the role of lncRNAs like NEAT1 and C9orf72-as in ALS pathogenesis mechanisms caused by mutations in different genes, including TAR DNA-binding protein-43 (TDP-43), fused in sarcoma (FUS), superoxide dismutase type 1 (SOD1). NEAT1 is a well-established lncRNA in ALS pathogenesis; hence, we elaborate on its involvement in forming paraspeckles, stress response, inflammatory response, and apoptosis. Furthermore, antisense lncRNAs (as-lncRNAs), a key group of transcripts from the opposite strand of genes, including ZEB1-AS1 and ATXN2-AS, are discussed as newly identified components in the pathology of ALS. Ultimately, we review the current standing of using lncRNAs as biomarkers and therapeutic agents and the future vision of further studies on lncRNA applications.

Effects of non-pharmacological interventions on gait and balance of persons with Multiple Sclerosis: A narrative review.

BACKGROUND: Multiple Sclerosis (MS) is among the most common reasons for disability in young adults. Mobility impairment, primarily related to gait and balance, is ranked as the preeminent concern among persons with MS (PwMS). Gait and balance dysfunction can directly affect the quality of life and activities of daily life in PwMS, hence the importance of effective treatment strategies. Previous studies have demonstrated the positive effect of various non-pharmacological rehabilitation methods, including physiotherapy and electrical stimulation, on gait and mobility in PwMS. Non-pharmacological methods can be tailored to the individual needs and abilities of each patient, allowing healthcare providers to create personalized training programs. Furthermore, these methods typically result in minimal or no side effects. PURPOSE: This review provides a comprehensive overview of an array of non-pharmacological treatment approaches aimed at enhancing ambulatory performance in PwMS. METHODS: We performed a narrative review of the original papers available in PubMed, investigating the effects of different nonmedical approaches on the gait and balance performance of the PwMS. Reviewed treatment approaches include "exercise, physical rehabilitation, dual-task (DT) rehabilitation, robot-assisted rehabilitation, virtual reality-assisted rehabilitation, game training, electrical stimulation devices, auditory stimulation, visual feedback, and shoe insoles". RESULTS AND CONCLUSIONS: Eighty articles were meticulously reviewed. Our study highlights the positive effects of non-pharmacological interventions on patients' quality of life, reducing disability, fatigue, and muscle spasticity. While some methods, including exercise and physiotherapy, showed substantial promise, further research is needed to evaluate whether visual biofeedback and auditory stimulation are preferable over conventional approaches. Additionally, approaches such as functional electrical stimulation, non-invasive brain stimulation, and shoe insoles demonstrate substantial short-term benefits, prompting further investigation into their long-term effects. Non-pharmacological interventions can serve as a valuable complement to medication-based approaches.

Long non-coding RNA as a potential diagnostic and prognostic biomarker in melanoma: A systematic review and meta-analysis.

Recently, long noncoding RNAs (lncRNAs) have been applied as biomarkers for melanoma patients. In this systematic review and meta-analysis, we investigated the diagnostic and prognostic value of lncRNAs. We used the keywords 'lncRNA' and 'melanoma' to search databases for studies published before June 14th, 2023. The specificity, sensitivity and AUC were utilized to assess diagnostic accuracy and the prognostic value was assessed using overall survival, progression-free survival and disease-free survival hazard ratios. After screening 1191 articles, we included seven studies in the diagnostic evaluation section and 17 studies in the prognosis evaluation section. The Reitsma bivariate model estimated a cumulative sensitivity of 0.724 (95% CI: 0.659-0.781, p < 0.001) and specificity of 0.812 (95% CI: 0.752-0.859, p < 0.001). The pooled AUC was 0.780 (95% CI: 0.749-0.811, p < 0.0001). The HR for overall survival was 2.723 (95% CI: 2.259-3.283, p < 0.0001). Two studies reported an HR for overall survival less than one, with an HR of 0.348 (95% CI: 0.200-0.607, p < 0.0002). The HR for progression-free survival was 2.913 (95% CI: 2.050-4.138, p < 0.0001). Four studies reported an HR less than one, with an HR of 0.457 (95% CI: 0.256-0.817). The HR for disease-free survival was 2.760 (95% CI: 2.009-3.792, p < 0.0001). In conclusion, the expression of lncRNAs in melanoma patients affects survival and prognosis. LncRNAs can also be employed as diagnostic biomarkers.

Brain-derived neurotrophic factor in fibromyalgia: A systematic review and meta-analysis of its role as a potential biomarker.

BACKGROUND: Fibromyalgia (FM) is a form of chronic pain disorder accompanied by several tender points, fatigue, sleeping and mood disturbances, cognitive dysfunction, and memory problems. Brain-derived neurotrophic factor (BDNF) is also a mediator of neurotrophin for many activity-dependent processes in the brain. Despite numerous research studies investigating BDNF in FM, contradictory results have been reported. Thus, we investigated the overall effect shown by studies to find the association between peripheral BDNF concentrations and its gene polymorphisms with FM. METHODS: A systematic search in online international databases, including PubMed, Cochrane Library, Embase, the Web of Science, and Scopus was performed. Relevant studies assessing BDNF levels or gene polymorphism in patients with FM and comparing them with controls were included. Case reports, reviews, and non-English studies were excluded. We conducted the random-effect meta-analysis to estimate the pooled standardized mean difference (SMD) or odds ratio (OR) and 95% confidence interval (CI). RESULTS: Twenty studies were found to be included composed of 1,206 FM patients and 1,027 controls. The meta-analysis of 15 studies indicated that the circulating BDNF levels were significantly higher in FM (SMD 0.72, 95% CI 0.12 to 1.31; p-value = 0.02). However, no difference between the rate of Val/Met carrier status at the rs6265 site was found (p-value = 0.43). Using meta-regression, the sample size and age variables accounted for 4.69% and 6.90% of the observed heterogeneity of BDNF level analysis, respectively. CONCLUSION: Our meta-analysis demonstrated that FM is correlated with increased peripheral BDNF levels. This biomarker's diagnostic and prognostic value should be further investigated in future studies.

Triglyceride-glucose index and heart failure: a systematic review and meta-analysis.

BACKGROUND: Insulin resistance (IR) is a major metabolic disorder observed in heart failure (HF) and is tightly associated with patients' poor prognosis. The triglyceride-glucose index (TyG) has been proposed as a surrogate marker of IR in HF. Yet, whether TyG is a reliable clinical marker is still under debate. Hence, we aimed to respond to this relevant question via a systematic review and meta-analysis of existing studies. METHODS: A systematic search was conducted in PubMed, Embase, Scopus, and Web of Science to find studies investigating the TyG index in patients with HF or its association with the incidence of HF. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) were pooled through random-effect meta-analysis. HRs were calculated using TyG as a continuous variable (1 unit increase) and by comparing the group with the highest TyG to the lowest TyG group. RESULTS: Thirty studies, involving 772,809 participants, were included in this systematic review. Meta-analysis of seven studies comparing the highest-TyG to the lowest-TyG group showed a significantly increased risk of HF in the former group (HR 1.21, 95% CI 1.14 to 1.29, P < 0.01). The same result was found when pooling the HRs for a one-unit increase in the TyG index (HR 1.17, 95% CI 1.08 to 1.26). Similarly, a more elevated TyG index was associated with a higher incidence of HF in patients with type 2 diabetes or coronary artery disease. Additionally, the incidence of adverse events (readmission and mortality) in patients with HF was associated with TyG. CONCLUSION: Our findings support the TyG index as a valuable marker to assess the risk of HF incidence in different populations and as a prognostic marker in patients with HF. Further studies should be conducted to confirm these associations and investigate the clinical utility of the TyG index.

Long non-coding RNA as a potential diagnostic biomarker in head and neck squamous cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies arising from the epithelium of the head and neck. Despite efforts in treatment, results have remained unsatisfactory, and the death rate is high. Early diagnosis of HNSCC has clinical importance due to its high rates of invasion and metastasis. This systematic review and meta-analysis evaluated the diagnostic accuracy of lncRNAs in HNSCC patients. METHODS: PubMed, ISI, SCOPUS, and EMBASE were searched for original publications published till April 2023 using MeSH terms and free keywords "long non-coding RNA" and "head and neck squamous cell carcinoma" and their expansions. The Reitsma bivariate random effect model pooled diagnostic test performance for studies that reported specificity and sensitivity; diagnostic AUC values from all trials were meta-analyzed using the random effects model with the inverse variance method. RESULTS: The initial database search yielded 3209 articles, and 25 studies met our criteria. The cumulative sensitivity and specificity for lncRNAs in the diagnosis of HNSCC were 0.74 (95%CI: 0.68-0.7 (and 0.79 (95%CI: 0.74-0.83), respectively. The pooled AUC value for all specimen types was found to be 0.83. Using the inverse variance method, 71 individual lncRNAs yielded a pooled AUC of 0.77 (95%CI: 0.74-0.79). Five studies reported on the diagnostic accuracy of the MALAT1 lncRNA with a pooled AUC value of 0.83 (95%CI: 0.73-0.94). CONCLUSIONS: LncRNAs could be used as diagnostic biomarkers for HNSCC, but further investigation is needed to validate clinical efficacy and elucidate mechanisms. High-throughput sequencing and bioinformatics should be used to ascertain expression profiles.

Particulate Matter Pollution Remains a Threat for Cardiovascular Health: Findings From the Global Burden of Disease 2019.

Background Particulate matter (PM) pollution is a significant risk factor for cardiovascular diseases, causing substantial disease burden and deaths worldwide. This study aimed to investigate the global burden of cardiovascular diseases attributed to PM from 1990 to 2019. Methods and Results We used the GBD (Global Burden of Disease) study 2019 to investigate disability-adjusted life-years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), and deaths attributed to PM as well as its subgroups. It was shown that all burden measures' age-standardized rates for PM were in the same decreasing trend, with the highest decline recorded for deaths (-36.7%). However, the all-age DALYs increased by 31%, reaching 8.9 million in 2019, to which YLLs contributed the most (8.2 million [95% uncertainty interval, 7.3 million-9.2 million]). Men had higher deaths, DALYs, and YLLs despite lower years lived with disability in 2019 compared with women. There was an 8.1% increase in the age-standardized rate of DALYs for ambient PM; however, household air pollution from solid fuels decreased by 65.4% in the assessed period. Although higher in men, the low and high sociodemographic index regions had the highest and lowest attributed YLLs/YLDs ratio for PM pollution in 2019, respectively. Conclusions Although the total age-standardized rate of DALYs for PM-attributed cardiovascular diseases diminished from 1990 to 2019, the global burden of PM on cardiovascular diseases has increased. The differences between men and women and between regions have clinical and policy implications in global health planning toward more exact funding and resource allocation, in addition to addressing inequity in health care access.

Survival outcomes and quality of life after percutaneous cryoablation for liver metastasis: A systematic review and meta-analysis.

BACKGROUND: Liver metastasis is present in a wide range of malignancies, with colorectal cancer as the most common site. Several minimally invasive treatments have been suggested for managing hepatic metastases, and cryoablation is among them, yet not widely used. In this systematic review, we aimed to assess the effectiveness of percutaneous cryoablation in all types of liver metastases. METHODS: A systematic search was performed in international databases, including PubMed, Scopus, Embase, and Web of Science, to find relevant studies reporting outcomes for percutaneous cryoablation in liver metastasis patients. In addition to baseline features such as mean age, gender, metastasis origin, and procedure details, procedure outcomes, including overall survival, local recurrence, quality of life (QoL), and complications, were extracted from the studies. Random-effect meta-analysis was performed to calculate the mean difference (MD) and 95% confidence interval for comparison of QoL. RESULTS: We screened 2131 articles. Fifteen studies on 692 patients were included. Mean overall survival ranged from 14.5-29 months. The rate of local recurrence in the included studies ranged from 9.4% to 78%, and local control progression-free survival ranged from 1 to 31 months. The total QoL decreased one week after the cryoablation procedure (-3.08 [95% Confidence interval: -4.65, -1.50], p-value <0.01) but increased one month (5.69 [3.99, 7.39], p-value <0.01) and three months (3.75 [2.25, 5.24], p-value <0.01) after the procedure. CONCLUSION: Cryoablation is an effective procedure for the treatment of liver metastases, especially in cases that are poor candidates for liver resection. It could significantly improve QoL with favorable local recurrence.

CT-guided Transgluteal Prostate Fiducial Marker Insertion for Localized Radiation Therapy.

PURPOSE: To Evaluate the safety and technical success of transgluteal CT-guided fiducial marker implantation into the prostate as an alternative method to transperineal and transrectal approaches. MATERIAL AND METHODS: We retrospectively identified all patients who had undergone CT-guided transgluteal fiducial marker insertion between 2020 and 2022. Four patients with confirmed prostate cancer were identified. One radiologist performed all procedures via a bilateral transgluteal approach under the guidance of real-time CT-fluoroscopy. Twenty cm long pre-waxed 18G guiding needles, preloaded with smooth gold fiducial markers, were used to implant markers. Technical success was defined as the successful placement of the fiducial markers into the planned positions. RESULTS: The mean age of patients was 70 years. The mean procedure time was 19.25 (SD: 6.75) min, and the mean total dose length product (DLP) was 801.75 (SD: 291.17) mGycm, which is compatible with the 12 mSv estimated effective dose. All procedures were technically successful (100%). All patients tolerated the procedure and did not require any analgesia for pain, and there were no requests to stop or pause the procedure. Only one patient reported hematuria one day after the procedure, which required no treatment. CONCLUSION: Transgluteal CT-guided fiducial marker implantation into the prostate is an alternative method to transperineal and transrectal approaches. In this technique, the risk of septic complications is minor, and general anesthesia is not required. Thus, transgluteal CT-guided marker insertion is a feasible and well-tolerated method for image-guided radiation therapy (IGRT) in patients with prostate cancer.

NOD-like receptors in the pathogenesis of metabolic (dysfunction)-associated fatty liver disease: Therapeutic agents targeting NOD-like receptors.

BACKGROUND AND AIMS: In metabolic (dysfunction)-associated fatty liver disease (MAFLD), activation of inflammatory processes marks the transition of simple steatosis to steatohepatitis, which can further evolve to advanced fibrosis or hepatocellular carcinoma. Under the stress of chronic overnutrition, the innate immune system orchestrates hepatic inflammation through pattern recognition receptors (PRRs). Cytosolic PRRs that include NOD-like receptors (NLRs) are crucial for inducing inflammatory processes in the liver. METHODS: A literature search was performed with Medline (PubMed), Google Scholar and Scopus electronic databases till January 2023, using relevant keywords to extract studies describing the role of NLRs in the pathogenesis of MAFLD. RESULTS: Several NLRs operate through the formation of inflammasomes, which are multimolecular complexes that generate pro-inflammatory cytokines and induce pyroptotic cell death. A multitude of pharmacological agents target NLRs and improve several aspects of MAFLD. In this review, we discuss the current concepts related to the role of NLRs in the pathogenesis of MAFLD and its complications. We also discuss the latest research on MAFLD therapeutics functioning through NLRs. CONCLUSIONS: NLRs play a significant role in the pathogenesis of MAFLD and its consequences, especially through generation of inflammasomes, such as NLRP3 inflammasomes. Lifestyle changes (exercise, coffee consumption) and therapeutic agents (GLP-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, obeticholic acid) improve MAFLD and its complications partly through blockade of NLRP3 inflammasome activation. New studies are required to explore these inflammatory pathways fully for the treatment of MAFLD.

Cerebellar Microstructural Abnormalities in Obsessive-Compulsive Disorder (OCD): a Systematic Review of Diffusion Tensor Imaging Studies.

Previous neuroimaging studies have suggested that obsessive-compulsive disorder (OCD) is associated with altered resting-state functional connectivity of the cerebellum. In this study, we aimed to describe the most significant and reproducible microstructural abnormalities and cerebellar changes associated with obsessive-compulsive disorder (OCD) using diffusion tensor imaging (DTI) investigations. PubMed and EMBASE were searched for relevant studies using the PRISMA 2020 protocol. A total of 17 publications were chosen for data synthesis after screening titles and abstracts, full-text examination, and executing the inclusion criteria. The patterns of cerebellar white matter (WM) integrity loss, determined by fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) metrics, varied across studies and symptoms. Changes in fractional anisotropy (FA) values were described in six publications, which were decreased in four and increased in two studies. An increase in diffusivity parameters of the cerebellum (i.e., MD, RD, and AD) in OCD patients was reported in four studies. Alterations of the cerebellar connectivity with other brain areas were also detected in three studies. Heterogenous results were found in studies that investigated cerebellar microstructural abnormalities in correlation with symptom dimension or severity. OCD's complex phenomenology may be characterized by changes in cerebellar WM connectivity across wide networks, as shown by DTI studies on OCD patients in both children and adults. Classification features in machine learning and clinical tools for diagnosing OCD and determining the prognosis of the disorder might both benefit from using cerebellar DTI data.

Long non-coding RNA as a novel biomarker and therapeutic target in aggressive B-cell non-Hodgkin lymphoma: A systematic review.

Cancer initiation and progression have been associated with dysregulated long non-coding RNA (lncRNA) expression. However, the lncRNA expression profile in aggressive B-cell non-Hodgkin lymphoma (NHL) has not been comprehensively characterized. This systematic review aims to evaluate the role of lncRNAs as a biomarker to investigate their future potential in the diagnosis, real-time measurement of response to therapy and prognosis in aggressive B-cell NHL. We searched PubMed, Web of Science, Embase and Scopus databases using the keywords "long non-coding RNA", "Diffuse large B-cell lymphoma", "Burkitt's lymphoma" and "Mantle cell lymphoma". We included studies on human subjects that measured the level of lncRNAs in samples from patients with aggressive B-cell NHL. We screened 608 papers, and 51 papers were included. The most studied aggressive B-cell NHL was diffuse large B-cell lymphoma (DLBCL). At least 79 lncRNAs were involved in the pathogenesis of aggressive B-cell NHL. Targeting lncRNAs could affect cell proliferation, viability, apoptosis, migration and invasion in aggressive B-cell NHL cell lines. Dysregulation of lncRNAs had prognostic (e.g. overall survival) and diagnostic values in patients with DLBCL, Burkitt's lymphoma (BL), or mantle cell lymphoma (MCL). Furthermore, dysregulation of lncRNAs was associated with response to treatments, such as CHOP-like chemotherapy regimens, in these patients. LncRNAs could be promising biomarkers for the diagnosis, prognosis and response to therapy in patients with aggressive B-cell NHL. Additionally, lncRNAs could be potential therapeutic targets for patients with aggressive B-cell NHL like DLBCL, MCL or BL.

Endocan in prediabetes, diabetes, and diabetes-related complications: a systematic review and meta-analysis.

BACKGROUND: Diabetes is one of the chronic conditions with a high burden all around the world. Macrovascular and microvascular involvement are among the common mechanisms by which diabetes can impact patients' lives. Endocan as an inflammatory endothelial biomarker has been shown to increase in several communicable and non-communicable diseases. Herein, we aim to investigate the role of endocan as a biomarker in diabetes as a systematic review and meta-analysis. METHODS: International databases, including PubMed, Web of Science, Scopus, and Embase were searched for relevant studies assessing blood endocan in diabetic patients. Estimation of the standardized mean difference (SMD) and 95% confidence interval (CI) for comparison of circulating endocan levels between diabetic patients and non-diabetic controls were conducted through random-effect meta-analysis. RESULTS: Totally, 24 studies were included, assessing 3354 cases with a mean age of 57.4 ± 8.4 years. Meta-analysis indicated that serum endocan levels were significantly higher in diabetic patients in comparison with healthy controls (SMD 1.00, 95% CI 0.81 to 1.19, p-value < 0.01). Moreover, in the analysis of studies with only type-2 diabetes, the same result showing higher endocan was obtained (SMD 1.01, 95% CI 0.78 to 1.24, p-value < 0.01). Higher endocan levels were also reported in chronic diabetes complications such as diabetic retinopathy, diabetic kidney disease, and peripheral neuropathy. CONCLUSION: Based on our study's findings, endocan levels are increased in diabetes, however, further studies are needed for assessing this association. In addition, higher endocan levels were detected in chronic complications of diabetes. This can help researchers and clinicians in recognizing disease endothelial dysfunction and potential complications.

COVID-19 as a trigger of Guillain-Barré syndrome: A review of the molecular mechanism.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic with serious complications. After coronavirus disease 2019 (COVID-19), several post-acute COVID-19 syndromes (PACSs) and long-COVID sequels were reported. PACSs involve many organs, including the nervous, gustatory, and immune systems. One of the PACSs after SARS-CoV-2 infection and vaccination is Guillain-Barré syndrome (GBS). The incidence rate of GBS after SARS-CoV-2 infection or vaccination is low. However, the high prevalence of COVID-19 and severe complications of GBS, for example, autonomic dysfunction and respiratory failure, highlight the importance of post-COVID-19 GBS. It is while patients with simultaneous COVID-19 and GBS seem to have higher admission rates to the intensive care unit, and demyelination is more aggressive in post-COVID-19 GBS patients. SARS-CoV-2 can trigger GBS via several pathways like direct neurotropism and neurovirulence, microvascular dysfunction and oxidative stress, immune system disruption, molecular mimicry, and autoantibody production. Although there are few molecular studies on the molecular and cellular mechanisms of GBS occurrence after SARS-CoV-2 infection and vaccination, we aimed to discuss the possible pathomechanism of post-COVID-19 GBS by gathering the most recent molecular evidence.

The Economic Burden of Malignant Brain Tumors.

Malignant brain tumors consist of primary malignant tumors and metastatic brain tumors. The global incidence and prevalence of CNS cancers are increasing, their mortality and morbidity are relatively higher than other cancers (e.g., bladder cancer), and the management of disease utilizes sophisticated and expensive diagnostic and therapeutic technology. Therefore, malignant brain tumors, both primary and metastatic, impose a significant economic burden on patients, their families, and healthcare systems all around the world. To the best of our knowledge, there is no comprehensive and global systematic review for examining the costs of brain tumors, though sporadic reports highlight the importance of the problem. Besides, each study takes place in a setting with different methods (e.g., different treatment methods) and costs to manage brain tumors; therefore, we are unable to compare the costs between countries. Nevertheless, the general patterns seem to suggest that, among all, gliomas and glioblastomas are the most financially burdensome types of malignant brain cancer. Finally, most of the available studies have examined the economic burden of all gliomas or only glioblastoma. Hence, we are left with a substantial gap in knowledge to understand the actual economic burden of metastatic brain tumors, and there is a need for further accurate and internationally comparable studies on the subject, particularly with a focus on indirect and intangible costs.

Cryoablation for the Palliation of Painful Bone Metastasis: A Systematic Review.

BACKGROUND: Cryoablation is a minimally invasive procedure to treat painful bone metastases in patients with cancer. We designed a systematic review to understand the safety and effects of cryoablation on the pain and quality of life (QoL) of cancer patients. METHOD: We searched PubMed, ISI, Cochrane library, and Scopus databases using the keywords "Cryoablation," "Pain," and "Bone metastasis." Inclusion criteria were: (1) Original studies published until September 8, 2022; (2) studies on patients over 18 years and affected by bone metastasis; (3) bone metastasis treated with stand-alone cryoablation; (4) studies reporting patients' pain before and at least one time-point following cryoablation; and (5) English-language studies. RESULTS: We screened 696 articles. Fifteen studies on 376 patients were included. Time points for pain assessment ranged from 1 day to 6 months. Spine was the most frequent treated location. All studies reported a significant pain reduction between 1 day and 6 months after the cryoablation procedure. The highest mean difference between pre- and post-procedure scores was 5.8 (VAS scale) after 4 weeks. The overall rate of minor and major complications was 12.74%. Cryoablation improved the QoL of cancer patients and decreased the need for analgesics. CONCLUSION: Cryoablation is a safe and useful procedure for palliating painful bone metastasis and increasing the QoL of cancer patients. Future studies should adopt a standardized pain reporting scale to allow for meta-analysis.

CAR-NK cells: a promising cellular immunotherapy in lymphoma.

INTRODUCTION: New methods in cancer immunotherapy, such as chimeric antigen receptor (CAR)-T cells, have shown promising results in destroying malignant cells. However, limitations and side effects of CAR-T cell therapy, such as graft-versus-host disease (GVHD), neurotoxicity, and cytokine release syndrome, have motivated researchers to investigate safer alternative cells like natural killer (NK) cells. AREA COVERED: NK cells can effectively recognize hematologic malignant cells and destroy them. Many clinical and preclinical studies investigate the efficacy of CAR-NK cells in treating lymphoma and other hematologic malignancies. The results of published clinical trials and preclinical studies have shown that CAR-NK cells could be an appropriate choice for treating lymphoma. In this review, we discuss the characteristics of CAR-NK cells, their role in treating B-cell and T-cell lymphoma, and the challenges faced by using them. We also highlight clinical trials using CAR-NK cells for treating lymphoma. EXPERT OPINION: CAR-NK cells have shown promising results in cancer therapy, especially B-cell lymphoma, with a much lower risk for GVHD, cytokine release syndrome, and neurotoxicity than CAR-T cells. Further investigations are required to overcome the obstacles of CAR-NK cell therapy, both generally, and in cancers like T-cell lymphoma.

Association of lipid accumulation product with type 2 diabetes mellitus, hypertension, and mortality: a systematic review and meta-analysis.

Purpose: Novel anthropometric measures are simple, applicable, and inexpensive tools for cardiovascular risk assessment. This study evaluates the association of lipid accumulation product (LAP) with hypertension, type 2 diabetes mellitus (T2DM), and all-cause mortality, and compares it with other anthropometric measures. Methods: PubMed, Web of Science, EMBASE, and Scopus were systematically searched for articles published until May 15, 2021. We included all the studies that had measured LAP predictability for T2DM, all-cause mortality, and hypertension with no limitation in comorbidities and follow-up duration. We assessed the predictability measures of LAP for the aforementioned outcomes. We also performed a meta-analysis on four articles on mortality using an inverse variance method by the "meta" package in R software. Results: Twenty-nine studies were included in the review after applying the eligibility criteria. The hazard ratio for all-cause mortality per one standard deviation increment of LAP was 1.24 (95% confidence interval [CI]: 1.00-1.53; P = 0.0463) in females, and 1.07 (95% CI: 0.74-1.57; P = 0.709) in males. All included studies found a direct association between LAP with T2DM and hypertension. However, studies used different cut-off points for LAP. Most studies found that LAP was superior in predicting T2DM and hypertension compared to conventional indices, e.g., body mass index and waist circumference. We found that LAP may have higher prognostic significance in females compared to males. Conclusion: LAP is an inexpensive method to evaluate the risk of all-cause mortality, T2DM, and hypertension, and could outperform conventional anthropometric indices in this regard. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01114-z.

Toll-like receptors and metabolic (dysfunction)-associated fatty liver disease.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) is characterized by the accumulation of lipids in the liver (steatosis). In predisposed individuals, liver steatosis can progress to inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. The pathogenesis of MAFLD is complex and incompletely understood, involving various steatogenic, pro-inflammatory, and fibrogenic processes. Hyperactivation of the innate immune system through hepatic toll-like receptors (TLRs) contributes to the pathogenesis of MAFLD. Products of intestinal microbiota and danger signals from damaged hepatocytes constitute key ligands of TLRs that promote MAFLD. Most TLRs promote development and progression of MAFLD by induction of pro-inflammatory and pro-fibrogenic cytokines. Several nutraceutical and therapeutic agents improve MAFLD partly through the inhibition of hepatic TLRs. Herein, we review the available literature on hepatic TLR expression and signaling; crosstalk between gut microbiota and hepatic TLRs; and the contribution of TLRs to the pathogenesis of MAFLD. We also highlight implications for therapeutic approaches for MAFLD based on modulation of TLR signaling.

B- and T-Cell Subset Abnormalities in Monogenic Common Variable Immunodeficiency.

Common variable immunodeficiency (CVID) is a heterogeneous group of inborn errors of immunity characterized by reduced serum concentrations of different immunoglobulin isotypes. CVID is the most prevalent symptomatic antibody deficiency with a broad range of infectious and non-infectious clinical manifestations. Various genetic and immunological defects are known to be involved in the pathogenesis of CVID. Monogenic defects account for the pathogenesis of about 20-50% of CVID patients, while a variety of cases do not have a defined genetic background. Deficiencies in molecules of B cell receptor signaling or other pathways involving B-cell development, activation, and proliferation could be associated with monogenetic defects of CVID. Genetic defects damping different B cell developmental stages can alter B- and even other lymphocytes' differentiation and might be involved in the clinical and immunologic presentations of the disorder. Reports concerning T and B cell abnormalities have been published in CVID patients, but such comprehensive data on monogenic CVID patients is few and no review article exists to describe the abrogation of lymphocyte subsets in these disorders. Hence, we aimed to review the role of altered B- and T-cell differentiation in the pathogenesis of CVID patients with monogenic defects.