Diabetes-Associated Dry Eye Syndrome: Clinical Features, Underlying Molecular Mechanisms and Treatment Options

Pages 1-6

https://doi.org/10.22034/thr.2024.212234

Amirsaleh Abdollahi, Mehran Frouzanian

Abstract The global diabetes epidemic continues to rise, with complications extending beyond diabetic retinopathy (DR) and cataracts to include dry eye syndrome (DES), or keratoconjunctivitis sicca. Approximately 54% of individuals with diabetes experience DES, yet the condition remains poorly understood. Diabetes mellitus (DM) disrupts tear film homeostasis through mechanisms such as lacrimal gland dysfunction, Meibomian gland dysfunction, and abnormal tear dynamics. Chronic hyperglycemia, diabetic neuropathy, systemic inflammation, and altered mucin secretion exacerbate these changes, leading to tear instability and ocular surface damage. Risk factors for DES include advanced age, female sex, smoking, and higher glycated hemoglobin (HbA1c) levels. Surgical interventions for diabetes-related ocular complications, such as cataract surgery, intravitreal injections, and pan-retinal photocoagulation, further increase the risk of DES. Treatment strategies for diabetic dry eye (DMDES) include artificial tears, anti-inflammatory drugs like corticosteroids, cyclosporin A, tacrolimus, and autologous blood serum. However, these treatments address symptoms rather than underlying causes, with potential side effects. Emerging therapies, including gene-based approaches, show promise but require further research. Given the high prevalence of DMDES and its potential impact on quality of life, routine ocular surface and tear function assessments are recommended in diabetic care. Early diagnosis, glycemic control, and personalized treatment regimens are critical for preventing complications. Future studies must focus on targeted therapies to better manage DMDES and improve patient outcomes.
 

Exploring the Synergistic Potential of Combined Acupuncture and Repetitive Transcranial Magnetic Stimulation for Postpartum Depression

https://doi.org/10.22034/thr.2025.236685

Zamdar H Rasul Karim

Abstract Background: Postpartum depression (PPD) is a prevalent and serious global mental health disorder. Conventional pharmacological treatments like SSRIs have limitations, including side effects and breastfeeding safety concerns, prompting the exploration of alternative therapies.
Objective: This narrative review synthesizes current evidence on the efficacy, mechanisms, and clinical implementation of combined acupuncture and repetitive transcranial magnetic stimulation (rTMS) for PPD.
Methods: A narrative review was conducted to analyze and integrate existing research on the integrative use of acupuncture (a Traditional Chinese Medicine practice) and rTMS (a non-invasive neuromodulation technique) for treating PPD.
Results: Evidence suggests that combined acupuncture-rTMS therapy may produce synergistic effects. Potential benefits include a greater reduction in depressive symptoms, improved neuroendocrine regulation, and enhanced overall quality of life compared to either intervention administered alone.
Conclusion: The combination of acupuncture and rTMS represents a promising integrative approach for PPD. Further research is needed to optimize treatment protocols, identify predictive biomarkers, and evaluate long-term outcomes.

The Role of Varicocelectomy in Enhancing Fertility Outcomes: A Review Article

Pages 1-6

https://doi.org/10.22034/thr.2024.212236

Ahmad Deylami, Mehran Frouzanian, Mehdi Younesi Rostami, Behkam Rezaiemehr, Amirsaleh Abdollahi, Mohadeseh Modanlu, Maryam Shahbazinia, AmirReza Ranjbar, Fatemeh Rajabian

Abstract Varicocele is the leading cause of male infertility and can often be corrected or improved through a range of surgical and radiological methods. Consequently, it appears logical that varicocele should be treated in infertile men who have this condition. Varicocele, an enlargement of the pampiniform plexus veins affecting 15–20% of men, is more common in those with infertility concerns. Its impact on spermatogenesis is linked to oxidative stress, hypoxia, and immune responses, which may be alleviated by varicocelectomy. Varicocelectomy has been associated with improvements in sexual function, hormonal profiles, and fertility, particularly in men with hypogonadism. This review evaluates its effects on testosterone levels, semen quality, and fertility outcomes, highlighting the advantages of microsurgical varicocelectomy, such as improved sperm quality, higher spontaneous pregnancy rates, and fewer complications. However, patient outcomes depend on surgical indications, pre-existing conditions, and individual expectations.  Emerging evidence suggests that repairing varicoceles before assisted reproductive technology (ART) can enhance fertility outcomes. Further studies are needed to refine treatment criteria and expand options for diverse patient groups, including adolescents and men with pain-related varicoceles. The review also emphasizes the need for standardized diagnostic and treatment protocols.

The Influence of Stereotactic Body Radiotherapy (SBRT) on Biomarker Profiles in Lung Cancer: A Detailed Overview

https://doi.org/10.22034/thr.2025.236663

Babak Olia, Karomat Sobirova, Masharipova Ravqat, Madrimov Javoxir Islombek o'g'li, Niginabonu Khajiqurbonova, Fayzullayev Umidjon O'ktamovich, Ulliyeva Rayxon, Ataniyazov Aybek, Mahdi Hazratgholi

Abstract Background: Stereotactic Body Radiation Therapy (SBRT) represents the standard treatment for inoperable early-stage non-small cell lung cancer (NSCLC) and is increasingly utilized for oligometastatic disease. Its distinct radiobiological profile, involving high doses per fraction, triggers complex tumor-killing effects and systemic biological reactions not fully detectable through conventional imaging.
Objective: This review aims to summarize and critically assess current evidence regarding dynamic alterations in circulating, tissue, and imaging biomarkers after SBRT for lung cancer, and to explore their clinical significance.
Methods: A narrative synthesis of scientific literature from PubMed, Scopus, and Google Scholar was conducted, focusing on studies published between 2005 and 2024. Key search terms included "SBRT," "SABR," "lung cancer," "biomarker," "ctDNA," "immunotherapy," "cytokines," and "radiation pneumonitis."
Results: SBRT prompts a rapid, biphasic shift in tumor-derived biomarkers such as circulating tumor DNA (ctDNA), characterized by an initial post-treatment surge followed by reduction in responders. It significantly influences the immune system, inducing immunogenic cell death, expanding tumor-specific T-cell populations, and increasing checkpoint molecule expression like PD-L1. Additionally, SBRT modifies levels of cytokines (e.g., IL-6, TGF-β) and angiogenic factors (e.g., VEGF), which correlate with both treatment effectiveness and side effects like radiation-induced lung injury. Certain genetic polymorphisms also appear promising for predicting toxicity risk.
Conclusion: SBRT induces a dynamic and multifaceted change in the biomarker profile of lung cancer patients. These biomarkers offer considerable potential for personalizing treatment, predicting outcomes, monitoring response, and rationally planning combination therapies, especially with immunotherapy. Future prospective and validated studies are necessary to integrate these findings into clinical practice.

Pain Management and Anesthesia Considerations in Thyroid Carcinoma: An Emphasis on Anaplastic, Papillary, Follicular, Hurthle Cell, and Medullary Subtypes

Pages 1-7

https://doi.org/10.22034/thr.2024.212239

Amin Ghanbarpour Juybari, Amirsaleh Abdollahi, Alireza Karimi Varaki, Ali Pahnabi, Mehran Frouzanian, Mohamad Javad Bay, Mohammad Modarresi

Abstract Thyroid carcinoma encompasses a heterogeneous group of malignancies, each with distinct biological behaviors, therapeutic strategies, and challenges in pain management and anesthesia. This review delves into the subtypes of thyroid carcinoma—anaplastic, papillary, follicular, Hurthle cell, and medullary—emphasizing the critical interplay between effective pain control and surgical outcomes. Anaplastic thyroid carcinoma (ATC), characterized by rapid progression and local invasion, necessitates multimodal pain management, including systemic analgesics and nerve blocks, to address severe discomfort caused by structural compression. Papillary and follicular thyroid carcinomas, generally indolent but prone to recurrence, require tailored anesthesia and postoperative pain protocols, incorporating techniques like cervical plexus blocks to reduce opioid reliance. Unique challenges are posed by Hurthle cell carcinoma (HCC) and medullary thyroid carcinoma (MTC). HCC, often associated with poor prognosis, demands precise surgical techniques to enhance survival, while MTC involves hereditary and sporadic forms with systemic manifestations complicating pain management. Advanced surgical methods, including transoral and robotic thyroidectomy, are explored for their efficacy in reducing complications and enhancing patient satisfaction. For patients with genetic predispositions, early prophylactic surgeries significantly mitigate risks. Anesthesia considerations are paramount, particularly in advanced ATC, where airway management is crucial. Techniques such as total intravenous anesthesia (TIVA) and regional nerve blocks optimize perioperative outcomes while minimizing systemic side effects. This narrative underscores the importance of interdisciplinary collaboration and individualized care in addressing the multifaceted needs of thyroid carcinoma patients, ultimately aiming to improve survival rates and quality of life.

The Role of Early Intravenous Immunoglobulin and Nursing Process Optimization in Modulating Inflammation and Improving Outcomes in Pediatric Severe Adenovirus Pneumonia: A Comprehensive Review

https://doi.org/10.22034/thr.2025.236668

Salayeva Navbahor, Docent. Sevara Sadullayeva, Ollaberganov Zayniddin Umarbekovich, Niginabonu Khajiqurbonova, Sultanov Muhammad, Saginova Aygerim Sisenbayevna

Abstract Background: Severe adenovirus pneumonia (SAP) in children is a critical illness characterized by a dysregulated hyperinflammatory response. The adjunctive role of early intravenous immunoglobulin (IVIG) and optimized nursing care in modulating this inflammation remains a key area of clinical investigation.
Objective: This review evaluated current evidence on the efficacy of early IVIG administration and nursing process optimization (NPO) in improving clinical and biochemical outcomes for pediatric SAP.
Methods: A comprehensive analysis of clinical studies, including a pivotal randomized controlled trial was conducted. The review focuses on IVIG's immunomodulatory mechanisms and the impact of structured nursing interventions on care delivery.
Results: Early IVIG administration is associated with significant reductions in key inflammatory markers (CRP, PCT, IL-8) and leads to superior clinical outcomes, including shorter hospital stays, fever duration, and mechanical ventilation requirements, alongside lower complication rates. Concurrently, implementing NPO protocols dramatically reduces infusion-related adverse events.
Conclusion: The synergistic application of early IVIG and NPO presents a promising, holistic strategy for managing pediatric SAP by effectively modulating inflammation and enhancing the safety of care delivery. This combined approach warrants broader clinical adoption and further long-term study

Unraveling the Spectrum of Thyroid Carcinoma: From Aggressive Anaplastic to Curable Differentiated Forms - A Comprehensive Narrative Review

Pages 1-9

https://doi.org/10.22034/thr.2025.213077

Rostam Poormousa, Mehran Frouzanian, Amirsaleh Abdollahi, Mohamad Javad Bay, Kasra Hasannejad, Reza Talaei

Abstract Thyroid carcinoma encompasses a spectrum of malignancies with distinct clinical characteristics, management strategies, and prognoses. This narrative review article provides an in-depth examination of anaplastic thyroid carcinoma (ATC), papillary thyroid carcinoma (PTC), Hurthle cell carcinoma (HCC), and medullary thyroid carcinoma (MTC), offering insights into their epidemiology, diagnostic and treatment modalities. Anaplastic thyroid carcinoma is a highly aggressive and undifferentiated form of thyroid cancer, often associated with poor prognosis. Treatment strategies include combined resection and radiotherapy, but late-stage cases exhibit limited therapeutic options, emphasizing the need for novel therapeutic approaches. Papillary thyroid carcinoma, the most common thyroid cancer, generally carries a favorable prognosis. The article discusses surgical interventions like total thyroidectomy and lobectomy, along with minimally invasive techniques such as transoral endoscopic thyroidectomy vestibular approach (TOETVA) and robotic thyroidectomy. The importance of considering health-related quality of life in the treatment decision-making process is highlighted. Hurthle cell carcinoma, a rare and aggressive subtype, is explored with a focus on factors influencing prognosis. Surgical management, including thyroid lobectomy, completion thyroidectomy, and iodine-131 therapy, is discussed in detail. Medullary thyroid carcinoma is categorized into hereditary and sporadic forms, each requiring specific approaches. The review emphasizes the significance of genetic testing for patients at risk of multiple endocrine neoplasia syndrome (MEN2) and the need for early thyroidectomy in genetic RET mutation carriers. Furthermore, the article evaluates the extent of surgery, the role of radioiodine therapy, and the significance of follow-up in treating differentiated thyroid carcinomas (DTC). Surgical approaches for follicular thyroid carcinoma (FTC) and factors influencing the decision for total thyroidectomy versus lobectomy are elaborated upon. In summary, this narrative review provides a comprehensive overview of thyroid carcinoma subtypes, their epidemiology, surgical interventions, and postoperative management, offering valuable insights for clinicians and researchers in the field.
 

The Combined Impact of Preoperative Nutritional Support and Esketamine on Postoperative Recovery, Immune Function, and Quality of Life in Older Patients Receiving Thoracoscopic Lung Cancer Surgery

https://doi.org/10.22034/thr.2025.236686

Ismael Bilal Ismael, Sarwar Nawzad Jafar

Abstract Background: Older patients undergoing thoracoscopic radical resection for lung cancer face considerable risks of postoperative pain, weakened immunity, and malnutrition, which can slow recovery. Multimodal approaches are needed to enhance results. This review explores the combined benefits of preoperative nutritional support and analgesia based on esketamine.
Methods: A narrative literature review was performed using databases including PubMed, Embase, and the Cochrane Library up to 2025. The search targeted clinical trials, randomized controlled trials (RCTs), and meta-analyses on esketamine, preoperative nutrition, and outcomes in thoracic or cancer surgery. Information was combined to assess impacts on pain relief, immune and nutritional indicators, and recovery measures.
Results: Research consistently shows that esketamine notably decreases postoperative pain scores and opioid use while reducing opioid-related side effects. Preoperative immunonutrition lessens the surgery-related drop in immune markers (IgG, IgM, IgA) and nutritional proteins (Alb, TRF, PAB). Together, these approaches work synergistically to speed gastrointestinal recovery, reduce hospital stay, and improve health-related quality of life scores in older surgical patients.
Conclusion: Incorporating preoperative nutritional support and esketamine into Enhanced Recovery After Surgery (ERAS) protocols offers a promising multimodal method to improve perioperative care. This approach effectively manages pain, supports immune and nutritional health, and encourages quicker recovery, supporting broader clinical use and additional large-scale RCTs.

Predictive Modeling of Linezolid-Associated Hyponatremia in Critical Care: A Biomarker-Augmented Risk Framework

Pages 1-9

https://doi.org/10.22034/thr.2025.229209

Saaedeh Chalaki, Vahideh Chalaki, Seyyed Ghodsiyeh Esmaeilnejad, Seyyed Mohammad Hosseinnejad, Mona Foghani Ahangari

Abstract Background: Hyponatremia, a frequent yet potentially life-threatening electrolyte 
imbalance, poses heightened risks in intensive care contexts. This investigation sought to 
explore contributory factors linked to hyponatremia following linezolid administration in 
critically ill (CI) individuals and to formulate a robust predictive framework. 
Methods: A retrospective evaluation was conducted on clinical records and follow-up data 
from 200 CI patients who received linezolid therapy. To isolate key determinants, logistic 
regression modeling was utilized, followed by validation using Receiver Operating 
Characteristic (ROC) curve analysis. A nomogram-based risk assessment tool was then 
constructed, with calibration tested via the Hosmer-Lemeshow goodness-of-fit approach. 
Findings: Adverse reactions were recorded in 23.5% of the cohort. Statistically significant 
disparities (P < 0.05) emerged between CI and non-CI patients across several variables, 
including linezolid serum levels, therapy duration (DOM), baseline sodium values (BSS), 
estimated glomerular filtration rate (eGFR), white blood cell (WBC) count, total bilirubin 
(TBIL), albumin (ALB), and key biomarkers (NGAL, suPAR, Cystatin C), as well as concurrent 
spironolactone usage. The Z-score presented the highest diagnostic efficacy for 
hyponatremia, with a threshold of -3.24. The model demonstrated an 85.5% predictive 
accuracy, and the nomogram—based on multivariate regression and fit assessment—
 exhibited excellent alignment with actual outcomes. 
Interpretation: Independent predictors of hyponatremia included DOM, drug 
concentration, BSS, eGFR, and TBIL. Incorporation of novel biomarker profiles modestly 
improved model precision, suggesting added value in patient risk stratification. The 
developed tool offers promise for early detection and intervention in vulnerable ICU 
populations. 

Therapeutic Potential of Shugan Jieyu Capsule and Group Psychological Counseling for Alexithymia and Neuroimmune Dysfunction in Hemodialysis Patients

https://doi.org/10.22034/thr.2025.236659

Daniel S. Hamid

Abstract Background: Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) experience a high psychological burden, with frequent occurrences of alexithymia, anxiety, and depression. These psychological issues are increasingly associated with disruptions in neuroimmune and neuroendocrine pathways. This review examines the basis and supporting data for using a combined approach of Shugan Jieyu Capsule (SJC) and group psychological counseling (GPC) to target both the psychological and biological aspects of this complex condition.
Methods: A synthesis of existing literature was conducted, focusing on the pathophysiology of alexithymia in HD patients, the pharmacological effects of SJC, the therapeutic mechanisms of GPC, and the role of biomarkers such as Orphanin FQ (OFQ), Interleukin-2 (IL-2), Corticotropin-Releasing Hormone (CRH), Neurogranin, and soluble Fractalkine (sCX3CL1).
Results: Recent evidence indicates that a combined strategy of SJC and GPC is more effective than standard care alone. This integrated approach has been found to significantly reduce symptoms of alexithymia, anxiety, and depression; enhance sleep quality, self-care capacity, and social functioning; and improve overall quality of life. Importantly, these psychological improvements are associated with changes in key biomarkers, including decreased serum levels of OFQ, IL-2, CRH, Neurogranin, and sCX3CL1, suggesting a positive effect on stress response, synaptic function, and neuroinflammation.
Conclusion: The combination of Shugan Jieyu Capsule and group psychological counseling represents a promising, multi-targeted strategy for managing the psychosomatic challenges in hemodialysis patients. This method not only improves clinical symptoms but also appears to address underlying neuroimmune and neuroendocrine imbalances, offering a holistic approach to enhancing patient outcomes in ESRD care.

Muscle Morphology and Its Role in Chronic Neck Pain: A Review Article

Pages 1-11

https://doi.org/10.22034/thr.2025.509466.1007

Mehran Frouzanian, Seyed Sadegh Shirdel, Hosein Meskar, Mostafa Shahrezaee, Mostafa Chamanara, Amin Ghanbarpour Juybari, Amirsaleh Abdollahi

Abstract Introduction: Chronic neck pain (CNP) is a common and debilitating condition that significantly impacts quality of life, productivity, and overall well-being. Muscle morphology, particularly in the deep cervical muscles, plays a critical role in the onset, development, and persistence of chronic neck pain. This review investigates the relationship between muscle changes, including atrophy, fat infiltration, and alterations in muscle fiber composition, and their contribution to cervical instability, pain, and functional limitations.

Methods: The review examines existing literature on muscle morphology in CNP, focusing on the role of deep cervical muscles in the pathophysiology of neck pain. It also highlights how factors such as disuse, changes in neural activation, and chronic inflammation exacerbate these muscle alterations. The role of advanced imaging techniques, such as MRI, in identifying these changes is also discussed.

Results: Alterations in muscle morphology, including atrophy and fat infiltration, contribute to weakness and reduced spinal stability, which are key factors in the development and persistence of chronic neck pain. Neural activation changes and chronic inflammation further exacerbate muscle degeneration. Advanced imaging techniques, particularly MRI, play a crucial role in assessing these morphological changes and enabling personalized treatment strategies.

Conclusion: Muscle degeneration, including atrophy and fat infiltration in the cervical spine, is a significant factor in chronic neck pain. Effective management requires a comprehensive approach, including rehabilitation programs focused on muscle strengthening, postural correction, and ergonomic adjustments. Fat infiltration in cervical muscles is a significant marker of structural and functional impairment in cervical spine disorders. Further research is needed to explore the mechanisms behind muscle changes in CNP and to develop more targeted and effective interventions.

The Effectiveness of Combined Zoledronic Acid, Calcium, and Calcitriol Treatment for Osteoporosis in the Elderly: A Detailed Review of Bone Density, Metabolic Indicators, and Clinical Results

https://doi.org/10.22034/thr.2025.236681

Mohammed Ibrahim Mohialdeen Gubari

Abstract Introduction: Managing osteoporosis in the elderly, a common issue in aging populations worldwide, demands effective approaches to lower fracture risk and maintain life quality. Although calcium and vitamin D provide basic support, strong anti-resorptive drugs such as zoledronic acid are frequently required. This review compiles evidence on using zoledronic acid together with calcium and calcitriol to treat primary osteoporosis in older adults.
Methods: A narrative literature review was performed. Searches were conducted in electronic databases like PubMed, Scopus, and Web of Science for pertinent clinical trials, meta-analyses, and review articles published through 2024. Important search terms were "zoledronic acid," "senile osteoporosis," "bone mineral density," "bone turnover markers," "calcitriol," and "quality of life." Emphasis was placed on studies involving older populations and combinations of these treatments.
Results: Strong evidence shows that triple therapy (zoledronic acid, calcium, and calcitriol) is more effective than dual therapy (calcium and calcitriol alone) in substantially raising bone mineral density (BMD) at the lumbar spine, femoral neck, and hip. It creates a better bone metabolic state, marked by a significant reduction in resorption markers (CTX-1) and a subtle adjustment of formation markers (PINP, Osteocalcin). This treatment also leads to greater enhancements in quality of life scores (QUALEFFO-41) and shows a tolerable safety profile, with short-lived acute-phase reactions being the most frequent side effects.
conclusion: The combination treatment provides a synergistic, multi-target strategy. Zoledronic acid strongly hinders osteoclast-driven bone resorption, while calcium and calcitriol maintain a positive calcium balance and directly affect bone cell activity. This leads to stronger bones, decreased fracture risk, and better patient well-being. Long-term adherence and uncommon side effects are still factors to consider, but the benefit-risk balance is very positive for high-risk elderly patients.

Comparing Different Treatment Options for Plantar Fasciitis, A Review Article

Pages 1-7

https://doi.org/10.22034/thr.2025.509508.1008

Mostafa Shahrezaee, Seyed Sadegh Shirdel, Mohsen Chamanara, Hosein Meskar, Abolfazl Firouzian, Majid Sadeghi, Amirsaleh Abdollahi

Abstract Introduction: Plantar fasciitis is a prevalent condition characterized by chronic heel pain, primarily caused by inflammation of the plantar fascia. The condition significantly impairs daily activities and quality of life, presenting a challenge for healthcare providers. Numerous treatment modalities, ranging from conservative measures to invasive interventions, have been explored to manage the symptoms and promote healing. However, the effectiveness of these treatments, especially when combined, requires further evaluation.

Methods: This review extracted data from existing studies comparing the effectiveness of corticosteroid injections (CSI) alone versus their combination with needling techniques (such as dry needling and percutaneous needle electrolysis) for chronic plantar fasciitis. The literature was assessed through systematic reviews, randomized controlled trials, and clinical studies that evaluated pain relief, functional recovery, and long-term outcomes. Studies on adjunctive treatments like extracorporeal shockwave therapy (ESWT) were also considered to provide a broader comparison.

Results: Corticosteroid injections provide significant short-term pain relief but are limited in their long-term efficacy, with potential complications like tissue atrophy. Dry needling and other needling therapies, when used in combination with CSI, have shown improved long-term outcomes in terms of pain reduction and functional recovery. ESWT consistently outperformed other treatments in long-term studies for both pain management and functional improvement. Combining treatments appears to yield enhanced results, although conclusive evidence on optimal treatment protocols remains insufficient.

Conclusion: Chronic plantar fasciitis requires a multi-faceted treatment approach. While corticosteroid injections remain a common short-term solution, combining them with needling techniques may offer superior long-term benefits. Extracorporeal shockwave therapy also shows promise for sustained relief. Further research is needed to establish optimal treatment protocols and to better understand the combined effects of these interventions. An individualized treatment strategy that addresses both symptoms and underlying causes is essential for improving patient outcomes.

The Impact of Serum 25-Hydroxyvitamin D and Genetic Factors on Liver Cancer Risk: An Updated Review and Mendelian Randomization Analysis

https://doi.org/10.22034/thr.2025.236687

Priya Priyadarshini

Abstract Background: Liver cancer, mainly hepatocellular carcinoma (HCC), presents a major global health challenge with high mortality. While established risk factors such as viral hepatitis and alcohol consumption are widely recognized, there is growing interest in modifiable factors like vitamin D (VD) deficiency. Observational studies indicate a link between low serum 25-hydroxyvitamin D (25(OH)D) and increased liver cancer risk, though confounding factors and reverse causality complicate causal conclusions.
Objectives: This review aims to integrate current findings on the relationship between serum 25(OH)D and liver cancer risk, critically assess causality using Mendelian randomization (MR) evidence, and explore mechanistic insights from genetic research.
Methods: A narrative literature review was conducted using PubMed and Google Scholar, focusing on epidemiological studies, MR analyses, and mechanistic research published up to 2025. Search terms included "25-hydroxyvitamin D," "liver cancer," "hepatocellular carcinoma," "Mendelian randomization," and "genetic polymorphisms."
Results: Case-control and cohort studies consistently show that liver cancer patients have significantly lower serum 25(OH)D levels compared to healthy individuals. MR studies, using genetic variants in DHCR7CYP2R1, and VDR genes as instrumental variables, strongly indicate a causal protective effect of higher 25(OH)D concentrations on liver cancer risk. For example, alleles associated with increased 25(OH)D, such as those in DHCR7 (rs12785878) and VDR (rs2228570), correlate with a 20-30% reduction in liver cancer odds. These findings are supported by biological mechanisms, including VD's anti-proliferative, pro-apoptotic, and anti-inflammatory actions mediated through the VDR receptor in liver cells.
Conclusion: The alignment of epidemiological and genetic evidence reinforces the likely causal, protective role of vitamin D in liver cancer. Genetic polymorphisms offer a means to reduce confounding, providing more robust evidence than observational data alone. Future research should emphasize large-scale randomized controlled trials of VD supplementation in high-risk groups and further investigation of gene-environment

Post-Stroke Dysphagia: Clinical Screening with GUSS and Its Role in , Tailored Nutritional Therapy

Pages 1-10

https://doi.org/10.22034/thr.2025.229210

Saaedeh Chalaki, Hossein Montazer, Mirsaeed Ramazani

Abstract  Background: This investigation explored the clinical utility of the Gugging Swallowing 
Screen (GUSS) in identifying swallowing dysfunction following stroke and examined its 
application in designing individualized nutritional interventions. The study also assessed a 
set of physiological markers—brain-derived neurotrophic factor (BDNF), salivary cortisol, 
leptin, and growth differentiation factor-15 (GDF-15)—to determine their relationship with 
dysphagia severity, neural recovery, and clinical prognosis. 
Methods: A cohort of 174 individuals recovering from stroke underwent swallowing 
assessments using both the GUSS protocol and the traditional water swallow test (WST). 
Participants diagnosed with swallowing impairments were randomized into a control group 
(CG), which received standard medical care, and an observation group (OG), which received 
additional GUSS-guided stratified feeding regimens. Comparative analyses focused on 
changes in swallowing ability, emotional well-being, serum and salivary biomarker profiles, 
and occurrence of medical complications. 
Findings: GUSS outperformed WST in sensitivity and responsiveness (P < 0.05), as shown 
by significantly higher effect size (ES) and standardized response mean (SRM). Patients in 
the OG exhibited notably greater improvement in deglutition function and fewer adverse 
outcomes than those in the CG (P < 0.05). Post-treatment nutritional markers—albumin 
(Alb), prealbumin (PA), and transferrin (TNF)—were also more favorable in the OG. BDNF 
and leptin levels showed strong alignment with dysphagia grading, while elevated salivary 
cortisol was associated with stress-related swallowing issues. GDF-15 levels correlated 
significantly with dysphagia-related complications. Moreover, quality of life indicators—
 including mental, physical, and social dimensions—were significantly enhanced in the OG (P 
< 0.05). 
Conclusion: GUSS proves to be a robust tool for early detection of post-stroke swallowing 
disorders and offers added clinical value when used to guide dietary intervention. The 
inclusion of stress, neuroplasticity, and inflammatory biomarkers—particularly salivary 
cortisol and GDF-15—adds depth to severity assessment and supports the development of 
personalized rehabilitation pathways.

Enhancing Anti-PD-1 Antibody Treatment in Colorectal Cancer: The Contribution of Innovative Immune Boosters and Inhibiting the USP2-PD-L1 Pathway

https://doi.org/10.22034/thr.2025.236684

Sarhang Hasan Azeez

Abstract Background: Colorectal cancer (CRC) remains a major global health issue, with advanced stages difficult to treat. Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway have improved cancer care, but they work well only in a small group of CRC patients with high microsatellite instability (MSI-H). Most CRC cases are microsatellite stable (MSS) and do not respond to ICI treatment alone, highlighting the need for combined therapies.
Methods: This review summarizes recent studies from PubMed, Google Scholar, and clinical trial databases up to 2025 focusing on why CRC resists ICI treatment. It examines ways to modify the immunosuppressive tumor microenvironment (TME), including using immune-boosting agents and targeting proteins like USP2 that regulate PD-L1.
Results: The immunosuppressive TME in MSS-CRC limits the effectiveness of PD-1 blockers. Immune adjuvants, such as the peptide NCL-P2, can reshape the TME by activating immune cells, increasing T cell entry into tumors, and reducing T cell exhaustion. Additionally, recent studies show that USP2 helps stabilize PD-L1 in cancer cells. Blocking USP2 leads to PD-L1 breakdown, improving T cell attack and boosting anti-PD-1 therapy in lab studies.
Conclusion: Combining anti-PD-1 antibodies with treatments that alter the immunosuppressive TME—such as immune adjuvants to strengthen immune responses and USP2 inhibitors to lower PD-L1 levels—offers a promising multi-target strategy. This method could help overcome treatment resistance and extend immunotherapy benefits to more CRC patients.

Unraveling a Complex Case: A Multidisciplinary Exploration of Alveolar Hemorrhage, Jaundice, and Respiratory Distress in the Context of Leptospirosis

https://doi.org/10.22034/thr.2025.507495.1005

Shayan Sabeti Billandi, Masoud Maboudi, Amir Saleh Abdellahi

Abstract Leptospirosis is a globally distributed zoonotic infection, more prevalent in tropical and low-income regions due to high temperatures, humidity, rainfall, and poor socioeconomic conditions. Individuals in high-risk occupations, such as farmworkers, veterinarians, and slaughterhouse employees, are particularly vulnerable. Early symptoms include fever, headache, myalgia, and conjunctival inflammation. Prompt diagnosis via culture and agglutination tests, along with early antibiotic treatment, can reduce complications and speed recovery. Adhering to hygiene and workplace safety measures is crucial for infection prevention and control.

This report presents the case of a 45-year-old male with fever, jaundice, and multiple systemic symptoms, with a history of chronic kidney disease and recent rice paddy exposure. He was admitted to Razi Hospital in Qaemshahr, where his condition rapidly deteriorated, requiring multidisciplinary intervention from nephrology, infectious disease, pulmonology, and psychiatry specialists. Initial findings revealed severe thrombocytopenia (platelet count: 8,000) and elevated creatinine levels (6 mg/dL), prompting treatment with dexamethasone, ceftriaxone, fluid therapy, and dialysis. However, his worsening respiratory distress and alveolar bleeding led to ICU admission.

Leptospirosis was suspected based on occupational exposure and was confirmed by positive IgM antibodies in urine PCR. Despite intensive interventions—including dialysis, pleural fluid drainage, and Shaldon catheter placement—the patient developed progressive pulmonary complications and eventually succumbed.

This case highlights the diagnostic and management challenges of leptospirosis in a patient with preexisting comorbidities. It underscores the importance of a multidisciplinary approach in recognizing and addressing the complexities of infectious diseases in critical care settings.

The Causes of Long-Term Hospitalization of Patients in the Emergency Ward of Rouhani and Beheshti Hospital

https://doi.org/10.22034/thr.2025.236741

Mir Saeid Ramezani, Ghazaleh Nikjouyan, Mehdi Mohammadian, Farhad Bagherian, Gholamhosein Hajiaghaei Amir, Ali Alizadeh Khatir, Hemmatollah Gholinia

Abstract Introduction: The length of stay in the emergency department (ED) starts from entering the unit and does not end until the patient is discharged home, admitted to the hospital or until transferred to another department or other treatment center. This period of time indicates the optimal management of beds in the ED. It is used as a performance index to evaluate the quality of care in the ED and the evidence shows that a stay in the ED of more than 6 hours is associated with an increase in mortality and morbidity. Therefore, the present study aims to investigate the causes of long-term stay (more than 12 hours) patients in the ED of Ayatollah Rouhani Babol educational and treatment center is designed.
Research method: This research was cross-sectional-retrospective. The study population consisted of all patients who referred to the ED of Rohani Babol Hospital in 2022. Sampling was done in the form of the entire census of the studied community. Data was collected using a checklist from Rouhani Hospital in Babol city. The collection tool was a pre-made checklist that included basic and demographic information of the patients. If a file did not have the desired information, or was incomplete, it was excluded from the study.
Results: This study was conducted on 400 patients who referred to the ED of Ayatollah Rouhani and Shahid Beheshti hospitals, who stayed in the emergency ward for more than 12 hours. In this study, the average duration of hospitalization until the assignment of the patient by the emergency medicine specialist was 57.8±82.6 minutes. The average time from entering to leaving the ED was 31.8 ± 21.8 hours for men and 33.8 ± 24.4 hours for women. The average time from entering to leaving the ED in patients with a history of hypertension was 38.9 ± 27.1 hours, with a history of diabetes 37.6 ± 27.3 hours, and with a history of heart disease 36.5 ± 24.3 hours. It was statistically significant (p=0.001), (p=0.007) and (p=0.040) respectively). The difference between the average time of entering and leaving the ED with the way the patient left the emergency ward was not statistically significant (p=0.636). However, a statistically significant difference was observed between the average time of entering and exiting the ED with the level of triage (p=0.004) and the type of disease (p=0.001). The results of the one-way analysis of variance test showed that the difference in the average duration of hospitalization in the emergency medicine service until leaving the emergency medicine service, the difference in the average duration of assignment by emergency medicine to the visit of the specialist assistant (p=0.814) and the difference in the average duration of required tests From the request to the answer to the test (p=0.454), no significant statistical difference was observed in the age groups. However, the difference in the average time between entering and leaving the ED in the age groups was found to be statistically significant (p=0.001).
Conclusion: The length of stay is influenced by various demographic and clinical factors. Therefore, it is possible to predict the length of stay by applying data mining techniques on hospital admission data. This work can be a suitable tool for planning and optimal allocation of hospital resources.

Radiation Dose-Response Relationship in Patients with Stage III Non-Small Cell Lung Cancer

https://doi.org/10.22034/thr.2025.560131.1023

Sarwar Nawzad Jafar, Sabah Ali Muhammed

Abstract Background: The optimal radiation dose for stage III non-small cell lung cancer (NSCLC) remains unclear. This study aimed to investigate the radiation dose-response relationship in patients with stage III NSCLC treated with definitive radiation therapy.

Methods: This retrospective cohort study analyzed 376 patients with stage III NSCLC treated with definitive radiation therapy between 2010 and 2019. The study population had a median age of 68 years, with 64.9% being male and 89.4% having a performance status of ECOG 0-1. The median radiation dose was 66 Gy, with 74.5% of patients receiving conventional fractionation and 25.5% receiving hypofractionated radiation.

Results: The median overall survival (OS) was 24.5 months, with a 95% confidence interval (CI) of 13.1-32.9 months. For every 1 Gy increase in radiation dose, the hazard of death decreases by 6% (HR = 0.94, p < 0.001). Older age is associated with a higher hazard of death (HR = 1.02, p = 0.002). Poorer performance status (ECOG 2-3) is associated with a higher hazard of death compared to good performance status (ECOG 0-1) (HR = 1.63, p = 0.009). Histology other than adenocarcinoma is associated with a higher hazard of death (HR = 1.55, p = 0.02). The results of the PCA suggest that the 15 dosimetric variables can be reduced to 5 components that explain 88.4% of the variance in the data suggesting that higher doses to smaller tumor volumes may be associated with better treatment outcomes.

Conclusion: Higher radiation doses may be associated with improved OS, but in patients with smaller tumor size. Further studies are needed to confirm these findings and to determine the optimal radiation dose for this patient population.

Exploring the Causal Role of Immune Cells in Autoimmune Hepatitis: A Narrative review of Mendelian Randomization Insights

https://doi.org/10.22034/thr.2025.236688

Sarhang Hasan Azeez

Abstract Background: Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease with an incompletely understood etiology. Observational studies suggest dysregulated immunity, but confounding and reverse causation have hindered causal inference. Mendelian randomization (MR) uses genetic variants as instrumental variables to assess causality and has recently been applied to investigate immune involvement in AIH.
Objective: To summarize and interpret findings from a recent bidirectional two-sample MR study evaluating the causal effects of 731 immune cell traits on AIH risk, contextualizing them within existing immunological knowledge.
Methods: This narrative review focuses on a key MR investigation using genome-wide association study (GWAS) summary statistics for 731 immunophenotypes and AIH. The primary analysis method was inverse variance weighting, supplemented by sensitivity analyses (MR-Egger, weighted median) and reverse MR to assess robustness and directionality of causal relationships.
Conclusion: The MR analysis provides genetic evidence supporting a causal role for specific innate and adaptive immune cell subsets in AIH pathogenesis. These findings highlight the therapeutic potential of targeting pathways involving myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), dendritic cells, NKT cells, and the PD-1/PD-L1 axis, offering a foundation for future mechanistic and translational research.
 

Awareness, Attitude, and Performance of Operating Room Technologists Toward the Prevention of Pressure Ulcers in Patients Candidate for Surgery

https://doi.org/10.22034/thr.2025.550143.1019

Fereshteh Sargolzaei, Moslem Birami, Afsaneh Poodineh, Jebraeil Farzi, Najme Ghiami Keshtgar

Abstract Background and purpose: Pressure ulcers are common postoperative complications that increase morbidity, mortality, and healthcare costs. Operating room (OR) technologists play a critical role in preventing pressure ulcers through proper skin care. This study aimed to assess the knowledge, attitude, and performance of OR technologists regarding skin care and pressure ulcer prevention.
Materials and methods: This descriptive-analytical, cross-sectional study was conducted from September to December 2022. Using a census sampling method, we included 58 operating room technologists from the educational hospitals affiliated with Zahedan University of Medical Sciences. Data were collected using a researcher-made questionnaire assessing knowledge, attitude, and performance. The data were analyzed using SPSS version 21, employing descriptive statistics, independent t-tests, and ANOVA.
Results: The mean and standard deviation of knowledge, attitude, and performance scores were 38.00 ± 15.00, 33.00 ± 6.00, and 23.00 ± 4.00, respectively. Most operating room technologists demonstrated a positive attitude, relatively good knowledge, and average performance toward pressure ulcer prevention. There was a significant relationship between knowledge scores and the age of operating room technologists (p < 0.0001).
Conclusion: The results of this study highlight the importance of knowledge, attitude, and performance among operating room professionals in reducing the risk of pressure ulcers in patients surgical candidates.. It can be suggested that in the field of skincare and prevention of pressure ulcers in the operating room, basic pressure ulcer training should be included at the beginning of the operating room courses and in the in-service training of operating room experts.

Current Insights into Pathophysiology, Clinical Presentation, and Minimally Invasive Management of Renal Peripelvic Cysts, A Narrative Review

https://doi.org/10.22034/thr.2025.563719.1031

Shahabaldin Bagheri, Behkam Rezaiemehr, Mojtaba Yousefi Zoshk, Masoud Maboudi, Amirsaleh Abdollahi, Mehdi Younesi Rostami, Mohammad Javad Bay, Ahmad Deylami

Abstract Background: Renal peripelvic (parapelvic) cysts cause hydronephrosis, pain, and obstruction when exceeding 4-5 cm due to hilar compression, with elevated IL-6, TNF-α, and creatinine reflecting inflammation and impaired function.​
Objective: This narrative review synthesizes evidence on pathophysiology, diagnosis, and minimally invasive management, emphasizing retroperitoneoscopic decortication versus ureteroscopic drainage outcomes.​
Methods: Literature from 2011-2025 (PubMed, Scopus, Web of Science) was reviewed, prioritizing comparative studies, case series (n≥20), and biomarker data; a key 100-patient cohort provided head-to-head analysis.​
Results: Retroperitoneoscopic decortication shows superior outcomes versus ureteroscopy: shorter operative time (78±18 vs 112±24 min), less blood loss (25±15 vs 55±30 mL), faster recovery (hospital stay 2.8±0.9 vs 5.1±1.4 days), lower complications (8% vs 18%), and greater IL-6/TNF-α decline; recurrence rates similar (8-10%).​
Conclusion: Retroperitoneoscopic decortication is optimal for symptomatic peripelvic cysts, balancing efficacy, safety, and biomarker recovery over ureteroscopy

Stereotactic Body Radiation Therapy for Oligometastatic Lung Cancer: A Retrospective Study of Predictors of Adverse Events

https://doi.org/10.22034/thr.2025.560122.1021

Ruaa Emad Al-Khalidi

Abstract Background: Oligometastatic lung cancer is a clinical entity characterized by a limited number of metastases, and stereotactic body radiation therapy (SBRT) has emerged as a promising treatment option for this condition. However, the relationship between SBRT dose and adverse events in this population is not well understood.


Objectives: To evaluate the treatment outcomes and adverse events associated with SBRT in patients with oligometastatic lung cancer, and to investigate the relationship between radiation dose and adverse events.


Methods: This retrospective chart review included 81 patients with oligometastatic lung cancer who underwent SBRT at a single institution between 2015 and 2023. Patients received SBRT with a dose of 30-60 Gy in 3-10 fractions. Data on patient demographics, tumor characteristics, treatment details, and adverse events were collected and analyzed.


Results: The study found that 37% of patients experienced adverse events of grade ≥2, with fatigue, dermatitis, and cough being the most common. Multivariate analysis revealed that higher radiation dose was significantly associated with increased risk of adverse events (OR 1.05, 95% CI 1.01-1.09, p=0.01). Other factors, including age, sex, ECOG performance status, and previous chemotherapy, were not significantly associated with adverse events.


Conclusion: This study demonstrates that SBRT higher radiation doses are associated with increased risk of adverse events with no other risk factor predicting adverse event occurrence. These findings highlight the importance of careful treatment planning and dose optimization to minimize toxicity while maintaining treatment efficacy.

A Comparative Analysis of Primary Radiotherapy versus Transoral Surgery for Early-Stage Laryngeal Squamous Cell Carcinoma: Oncologic and Functional Results

https://doi.org/10.22034/thr.2025.236666

Feruza Ruzimova, Sevara Sadullayeva, Madrimov Javoxir Islombek o'g'li, Niginabonu Khajiqurbonova, Fayzullayev Umidjon O'ktamovich, Xudoynazarova Dilnura, Uktamova Shoxida, Seyed Mohammad Hossein Mousavi

Abstract Backgrounds: Early-stage laryngeal squamous cell carcinoma (LSCC), which includes stage I and II disease, has a high cure rate. The main treatment approaches are definitive radiotherapy (RT) and transoral surgery (TOS), which includes transoral laser microsurgery (TLM) and transoral robotic surgery (TORS). Selecting the optimal treatment involves balancing oncologic effectiveness with functional results and quality of life.
Objective: To review and compare current evidence on overall survival (OS), disease-specific survival (DSS), laryngeal preservation (LP), and functional outcomes in early-stage LSCC treated with primary RT or TOS.
Methods: A narrative literature review was performed, identifying relevant studies from PubMed and Scopus. The focus was on peer-reviewed articles from the last two decades, including retrospective cohort studies, prospective trials, systematic reviews, and meta-analyses that directly compared RT and TOS.
Results: Recent large-scale analyses and meta-analyses show similar overall and disease-specific survival rates for T1 and T2 tumors treated with modern TOS or RT. The main differences are seen in patterns of oncologic control. TOS is linked to lower local recurrence but a higher incidence of second primary tumors, whereas RT shows higher local recurrence but a lower need for salvage laryngectomy, resulting in comparable long-term laryngeal preservation rates. Functionally, TOS offers advantages in treatment duration, voice outcomes for select T1a lesions, and cost-effectiveness, but may lead to poorer swallowing outcomes for larger resections. RT may provide better voice quality for more extensive T1 and T2 lesions but carries risks of long-term dry mouth and tissue scarring.
Conclusion: Both RT and TOS are effective treatments for early-stage LSCC, with similar long-term survival outcomes. Treatment selection should be individualized, based on tumor characteristics, patient health, institutional experience, and patient preferences regarding functional trade-offs and treatment burden.

Cost-Effectiveness Analysis of Radiation Therapy versus Surgery for Early-Stage Laryngeal Squamous Cell Carcinoma (T1-T2)

https://doi.org/10.22034/thr.2025.560126.1022

Sara Sarood Alnaqishbandi, Sabah Ali Mohammed

Abstract Background: Early-stage laryngeal squamous cell carcinoma (T1-T2) can be treated with either radiation therapy or surgery, but the cost-effectiveness of these treatments is unclear.

Methods: This study is a cost-effectiveness analysis comparing radiation therapy and surgery as treatments for early-stage laryngeal squamous cell carcinoma (T1-T2) at a university hospital's tertiary care center. A consecutive sampling method was used to select 86 patients (43 per group) diagnosed with early-stage laryngeal squamous cell carcinoma (T1-T2) between January 2018 and December 2020. Demographic, clinical, and cost data were collected, and quality of life data were collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).

Results: The mean total cost for patients treated with radiation therapy was ¥123,419, which was significantly lower than the mean total cost for patients treated with surgery (¥153,219, p=0.012). The mean QALYs for patients treated with radiation therapy was 4.21 (± 1.23), which was slightly higher than the mean QALYs for patients treated with surgery (3.92 ± 1.35), but the difference was not statistically significant (p=0.142). The incremental cost-effectiveness ratio (ICER) was ¥24,011 per QALY gained, indicating that radiation therapy was associated with a lower cost per QALY gained compared to surgery. At a willingness-to-pay (WTP) threshold of ¥50,000 per QALY, the probability that radiation therapy is cost-effective is 72.1%.

Conclusion: Radiation therapy is a cost-effective treatment option for early-stage laryngeal squamous cell carcinoma (T1-T2) compared to surgery, with a lower ICER and a higher probability of cost-effectiveness at various WTP thresholds. These findings can inform treatment decisions and resource allocation in the management of early-stage laryngeal squamous cell carcinoma.