The Confounding Role of Graft-Versus-Host Disease in Animal Models of Cancer Immunotherapy: A Systematic Review.

BACKGROUND: Cancer immunotherapy has emerged as a transformative approach for treating various malignancies, including melanoma, lung cancer, breast cancer, and leukemia. Animal models have been instrumental in elucidating the mechanisms and potential of these therapies. However, graft-versus-host disease (GVHD) is an inherent challenge in these studies, primarily because the introduction of foreign immune cells or tissues often triggers immune responses. METHODS: A detailed systematic search was conducted across various scientific databases, including PubMed, Scopus, Embase, and Web of Science. The search aimed to identify peer-reviewed articles published in English from January 2000 to September 2023. Keywords and phrases used in the search included "Graft-versus-Host Disease", "GVHD", "animal models", "cancer immunotherapy", and combinations thereof. Boolean operators (AND/OR) were employed to refine the search. Finally, 6 articles were included in this systematic review, which is registered on PROSPERO (ID number CRD42024488544). RESULTS: Our systematic review identified several mechanisms employed in animal studies to mitigate the confounding effects of GVHD. These included genetically modified mouse models, immunosuppressive drugs, and humanized mice. Furthermore, the review highlights innovative approaches such as selective T-cell depletion and the use of specific cytokine inhibitors. CONCLUSION: By systematically identifying and mitigating the confounding effects of GVHD, we can significantly improve the predictive validity of preclinical trials, obtain broadly applicable findings, improve the efficiency of drugs, enhance safety profiling, and develop better therapeutic strategies. This approach is crucial in ensuring that the immunotherapeutic strategies developed in the laboratory are reflective of the human physiological response, thereby bridging a critical translational gap in oncological research.

The association of pro-oxidant/antioxidant balance and blood parameters in patients with beta-thalassemia major: a cross-sectional study.

Background: Oxidative stress due to iron accumulation in patients with beta-thalassemia major (BTM) causes complications such as tissue damage and destruction. This study aimed to assess the association between the serum prooxidant/antioxidant balance (PAB) and blood parameters in patients with BTM. Methods: This cross-sectional study included 92 patients with BTM. In this study, PAB was measured using an enzyme-linked immunosorbent assay (ELISA). Serum ferritin, blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), thyroid-stimulating hormone (TSH), total cholesterol (TC), triglyceride (TG), complete blood cell count (CBC), and history of blood transfusion were recorded. The association of the blood parameters was assessed across the tertiles (T) of serum PAB (highest T vs. lowest T). Results: The results showed that high serum ferritin was directly associated with serum PAB [odds ratio (OR), 12.80; 95% confidence interval (CI), 2.98‒54.91; T3 vs. T1]. Also, direct associations were found for high TC (OR, 4.97; 95% CI, 1.42‒17.32; T3 vs. T1), high ALT (OR, 4.95; 95% CI, 1.33‒18.46; T3 vs. T1) and high TSH (OR, 3.78; 95% CI, 1.10‒13.02; T3 vs. T1). Conclusion: The findings of the present study showed that serum PAB levels were directly associated with ferritin, ALT, TC, and TSH levels. This indicates that improvements in blood parameters, especially ferritin and TSH levels, occur by ameliorating oxidative stress in patients with BTM.

Recent advances in the detection of glioblastoma, from imaging-based methods to proteomics and biosensors: A narrative review.

Glioblastoma (GBM) is an aggressive type of cancer that originates in the cells called astrocytes, which support the functioning of nerve cells. It can develop in either the brain or the spinal cord and is also known as glioblastoma multiform. GBM is a highly aggressive cancer that can occur in either the brain or spinal cord. The detection of GBM in biofluids offers potential advantages over current methods for diagnosing and treatment monitoring of glial tumors. Biofluid-based detection of GBM focuses on identifying tumor-specific biomarkers in blood and cerebrospinal fluid. To date, different methods have been used to detect biomarkers of GBM, ranging from various imaging techniques to molecular approaches. Each method has its own strengths and weaknesses. The present review aims to scrutinize multiple diagnostic methods for GBM, with a focus on proteomics methods and biosensors. In other words, this study aims to provide an overview of the most significant research findings based on proteomics and biosensors for the diagnosis of GBM.

Genomic and Personalized Medicine Perspective in Genetic Generalized Epilepsy.

The genetic generalized epilepsies (GGEs) are a set of disorders presenting with generalized seizures, in addition to general spike-wave activity. The present study aims to investigate the clinical manifestations and genetic origin of generalized tonicclonic seizures and the subgroups of GGEs, including childhood absence epilepsy (CAE), juvenile absence epilepsy, and juvenile myoclonic epilepsy (JME). Information compiled from genome-wide association studies (GWASs) in the EPICure project revealed associations with many genes. Besides, copy number variant (CNV) discoveries have been the most inspiring turning point of epilepsy genetic research. This phenomenon could give us an idea about microdeletions/microduplications as genetic variants throughout the whole genome. Nowadays, next-generation sequencing (NGS) approaches support neurogeneticists to unravel the predisposed putative variants in GGE to establish a better diagnosis. Consequently, previous experiments supply data for antiepileptic drugs (AEDs) to test susceptible variants, which influence the response to drugs. As a final point, all these data should provide the current GGE patients with better genetic counseling and follow-up services.

Effectiveness of Paromomycin on Cutaneous Leishmaniasis in Iran: A Systematic Review and Meta-Analysis.

BACKGROUND: Some treatment reported for cutaneous leishmaniasis. The studies examined the impact of the paromomycin has different characteristics and results. The aim of the present study was to conduct a systematic review and meta-analysis of all randomized clinical trials evaluating the effectiveness of paromomycin in the treatment of cutaneous leishmaniasis in Iran. METHODS: Literature search was conducted using MEDLINE, Web of Science, Scopus, Scientific Information Database, IranMedex, Magiran, Iranian Registry of Clinical Trials (from February 2000 to May 2016), and references cited in the text of selected studies. Search terms used were "paromomycin", "cutaneous leishmaniasis", "randomized"," aminosidine", "controlled trial", and "clinical trial". Random effects models were used to calculate the measure of association, with 95% confidence intervals, to analyze the efficacy of paromomycin in the treatment of cutaneous leishmaniasis. RESULTS: Initial search yielded 76 citations. Of these original results, 9 met our specific selection criteria. Four of the randomized controlled trials compared the efficacy of paromomycin in the treatment of cutaneous leishmaniasis with that of a placebo; they were included in the meta-analysis. The success rate of treatment with paromomycin was higher than that with the placebo (pooled RR=4.50, 95% CI: 2.54 to 8.02; P=0.001 and I2=26.7%), whereas the difference with the non-placebo treatments was nonsignificant (pooled RR=0.79, 95% CI: 0.58 to 1.073; P=0.131 and I2=83.3%). CONCLUSION: No significant difference was observed between paromomycin and the other treatments in their effectiveness in the treatment of cutaneous leishmaniasis. Because no single drug is effective against all the forms of leishmaniasis, we suggest multidrug therapy.

A case of recurrent hematuria in primary prostatic low grade mucosa associated lymphoid tissue.

BACKGROUND: Primary mucosa-associated lymphoid tissue (MALT) lymphoma is a rare malignancy. We found only 8 cases of MALT lymphoma in literature. CASE PRESENTATION: We report here another case of primary prostatic MALT lymphoma which is presented by hematuria and diagnosed primarily as BPH. Immunohistochemistry studies demonstrate the diagnosis and MALT lymphoma. Six months after starting the treatment the patient was alive and well. CONCLUSIONS: Prostatic MALTomas are mainly presented with urinary obstruction or hematuria and have an indolent growth with a good prognosis.

Transdermal fentanyl patches versus patient-controlled intravenous morphine analgesia for postoperative pain management.

BACKGROUND: Acute and severe pain is common in patients postoperatively and should be correctly managed. In the past years studies on preparing better postoperative pain control have resulted in development of postoperative pain management guidelines. Perhaps, one of the major improvements in managing postoperative pain is the development of the patient-controlled analgesia systems (PCA), especially through intra venous (IV), extradural and transdermal routes, which has resulted in marked improvements in acute postoperative pain management. Physicians administrate potent opioids for moderate to severe post-surgical pains. Morphine is the most commonly IV-PCA administrated analgesic. The fentanyl iontophoretic transdermal system (fentanyl ITS) is also another efficient option for pain management. OBJECTIVES: The aim of this study was to compare the analgesic effects of these two routine postoperative pain control systems. PATIENTS AND METHODS: We enrolled 281 patients (224 males, 57 females) in this blind randomized controlled clinical trial, who had undergone an orthopedic surgery, with the mean age of 33.91 ± 14.45 years. Patients were randomly divided into two groups; in group A patients received IV-morphine PCA pump and in group B fentanyl transdermal patches were attached on patients' arms. The severity of the pain was registered according to Visual Analogue Scale in specially designed forms by pain-trained nurses in two steps; first after the surgery and next before the beginning of analgesic effects. After 24 hours, the pain score was assessed again. RESULTS: No significant difference was observed in mean pain intensity score at the first patient assessment. Mean pain intensity scores were also similar in both groups at the last measured time point (P > 0.05). Differential pain intensity scores, showing the impacts of analgesic system on the pain experience of the patients was also similar between fentanyl patches (6.48 ± 2.20) and morphine PCIA (6.40 ± 1.80). (P > 0.05) Mean patient satisfactory score (scale: 0-100) was also similar in both groups (P > 0.05). The percentage of patients, whose differential pain intensity scores at 24 hours reached our pain management goal was similar between fentanyl and morphine groups (P > 0.05). The percentage of patients with at least one adverse event was significantly higher in fentanyl group (P < 0.05). The most frequent adverse events were nausea, vomiting and itching. In none of the groups, no patient experienced serious adverse events related to the studied medications. CONCLUSIONS: Although both pain killing therapeutic regimens are safe and effective for postoperative pain management, regarding the easy usage of the patches, lower risk of abuse and cost-effectiveness in the Iranian market, it is recommended for use in Iranian hospitals and trauma centers and in countries with similar socioeconomic situations.

Leech therapy in nearly total amputation of fingers without vascular repair: a case report.

INTRODUCTION: In the absence of microvascular replantation or in crash injury cases in which obtaining an acceptable function is not possible, amputation of the injured finger seems to be the best treatment modality. Some studies recommended leech therapy for this kind of injury after vascular repair to decrease venous congestion. CASE PRESENTATION: In this case report, the authors presented a case of leech therapy after near total amputation of the fingers. A 25-year-old patient was admitted following a sawing injury with crashed bundles of the third, fourth and fifth fingers. Microvascular surgery was not performed because of crush injury. DISCUSSION: After a simple repair and pin fixation, the patient was treated using leech therapy. The result was satisfactory. The third and fourth fingers were salvaged. It seems that in cases where a small part of the skin is still attached to the amputated part, even with complete crash of both bundles, leech therapy can help salvage the amputated fingers.

Knowledge and perception toward colorectal cancer screening in east of Iran.

BACKGROUND: Colorectal Cancer (CRC) is the third most common cancer in Iran and its early detection is necessary. This study is based on perception of people in the east of Iran toward CRC screening. METHODS: In a cross-sectional study, 1060 randomly selected individuals who referred to Razavi Hospital of Mashhad, Iran, between September the 1(st), 2012 and February the 28(th), 2013 as patients or their visitors involved in an interview to fill a questionnaire on CRC screening. RESULTS: The participants' age ranged from 40 to 88 years (mean= 55). More than 90% had no knowledge of CRC and screening tests. The most cited reasons for not having screening tests were "did not have any problem" and "did not think it was needed". Although, older people had more knowledge of CRC (P= 0.033), there was no relationship between gender, health insurance status, family history of individuals and their knowledge about CRC (P> 0.050). Employment, education and higher income had positive effect on the perception of people toward CRC screening (P< 0.050). CONCLUSION: Lack of knowledge in people in lower socio-economical class with limited literacy is the most important barrier to CRC screening. As such, designing educational programs involving physicians and media is important to improve CRC screening rates.

Effect of Self-regulation Training on Management of Type 2 Diabetes.

BACKGROUND: Diabetes is the most common metabolic disorder which is required to be taken under control. According to some studies, the impact of self-regulation on health has been considered as a monitoring strategy to achieve individual's goals. OBJECTIVES: This study, which was performed in 2012, aimed at determining the consequences of self-regulation on controlling type 2 diabetes. PATIENTS AND METHODS: In this double-blind clinical trial, 60 patients with type 2 diabetes - who were referred to Diabetes Clinic of Bisto-Dou Bahman Hospital in Gonabad, Iran - were divided randomly into case and control groups. Self-regulation questionnaire, nutritional information and physical activity checklists were completed by both groups once at the beginning and once at end of the training. Fasting blood sugar (FBS) of both groups were measured as well. Case group was trained for a month, whereas the control group received no special training. Data were analyzed by SPSS version 19 software, K-square and paired t-tests. RESULTS: Comparing the case with the control group before and after the training showed that teaching patients self-regulatory strategies had significant impact on lowering blood sugar (-16.50 vs. -2.47, P < 0.001), observing dietary behaviors (5.97 vs. -0.87, P < 0.001) and increasing physical activities (6.2 vs. -0.73, P < 0.001) of the former group. CONCLUSIONS: Learning self-regulations has a role to play in controlling type 2 diabetes. Therefore, it is suggested to professionals in healthcare centers to educate patients about self-regulatory techniques and use them as auxiliary methods for keeping type 2 diabetes under control.

Renal failure prevalence in poisoned patients.

BACKGROUND: Renal failure is an important adverse effect of drug poisoning. Determining the prevalence and etiology of this serious side effect could help us find appropriate strategies for the prevention of renal failure in most affected patients. OBJECTIVES: The present study is aimed to identify drugs that induce renal failure and also to find the prevalence of renal failure in patients referred to emergency departments with the chief complaint of drug poisoning, in order to plan better therapeutic strategies to minimize the mortality associated with drug poisoning induced renal failure. PATIENTS AND METHODS: This cross-sectional study surveyed 1500 poisoned patients referred to the Emergency Department of Baharloo Hospital in Tehran during 2010. Demographic data including age and gender as well as clinical data including type of medication, duration of hospital stay, and presence of renal failure were recorded. Mann-Whitney U test and chi-squared statistics were used to analyze the results. RESULTS: A total number of 435 patients were poisoned with several drugs, 118 patients were intoxicated with sedative-hypnotic drugs, 279 patients were exposed to opium, and 478 patients were administered to other drugs. The method of intoxication included oral 84.3%, injective 9%, inhalation 4.3% and finally a combination of methods 2.3%. Laboratory results revealed that 134 cases had renal failure and 242 had rhabdomyolysis. The incidence of rhabdomyolysis and renal failure increased significantly with age, and also with time of admission to the hospital. Renal failure was reported in 25.1% of patients exposed to opium, vs. 18.2% of patients poisoned with aluminum phosphide, 16.7% of those with organophosphate, 8% with multiple drugs, 6.7% with alcohol, heavy metals and acids, and 1.7% with sedative hypnotics. CONCLUSIONS: Based on the findings of this study, there is a high probability of renal failure for patients poisoned with drugs such as opium, aluminum phosphide, and multiple drugs as well as the patients with delayed admission to the hospital, and it is necessary to seek appropriate treatment to prevent this significant side effect.

A glance at methods for cleft palate repair.

CONTEXT: Cleft palate is the second most common birth defect and is considered as a challenge for pediatric plastic surgeons. There is still a general lack of a standard protocol and patients often require multiple surgical interventions during their lifetime along with disappointing results. EVIDENCE ACQUISITION: PubMed search was undertaken using search terms including 'cleft palate repair', 'palatal cleft closure', 'cleft palate + stem cells', 'cleft palate + plasma rich platelet', 'cleft palate + scaffold', 'palatal tissue engineering', and 'bone tissue engineering'. The found articles were included if they defined a therapeutic strategy and/or assessed a new technique. RESULTS: We reported a summary of the key-points concerning cleft palate development, the genes involving this defect, current therapeutic strategies, recently novel aspects, and future advances in treatments for easy and fast understanding of the concepts, rather than a systematic review. In addition, the results were integrated with our recent experience. CONCLUSIONS: Tissue engineering may open a new window in cleft palate reconstruction. Stem cells and growth factors play key roles in this field.

Coronary artery fistula: a huge conus branch aneurysm.

Coronary artery fistulas are rare coronary-cardiac anomalies, which occasionally become symptomatic. We herein report a case of a 54-year-old woman with a huge conus branch aneurysm resulting from an abnormal fistula between the conus branch and the upper portion of the right atrium, which was successfully removed by surgery.

Clinical outcome of ream versus unream intramedullary nailing for femoral shaft fractures.

BACKGROUND: Stabilization of fractures with an intramedullary nail is a widespread technique in the treatment of femoral shaft fractures in adults; however, to ream or not to ream is still being debated. OBJECTIVES: The primary objective of this study was to determine clinical results following unreamed versus ream intramedullary nailing of femoral fractures. PATIENTS AND METHODS: Between January 2008 and August 2009, 50 patients with femoral shaft fractures were treated with unreamed or reamed femoral nails in our clinic. From this prospective single centre study, 16 patients were excluded due to insufficient follow-up data. According to the AO classification, fractures in this study were either type A or B. Dynamic proximal locking was performed in all cases. The remaining 34 patients were divided into two groups of 17 with ream or unream nailing. During and after the operation, we evaluated some variables in whole series. RESULTS: After statistical analyzes, we found that there were no differences in radiologic union time (P = 1) or full weight bearing time (P = 0.73) between ream and unream nailing. Nail breakage or iatrogenic fractures during nail insertion did not occur and we did not have any fat emboli in both groups but one secondary loss of reduction occurred in the unream group. Superficial infection after the operation was seen in one case which was treated successfully with antibiotics. In the ream group surgical time was about thirty minutes longer and differences were significant (P = 0.000). Patients had to pay more for ream nailing but the difference was not significant. We found no statistical difference between union time with or without reaming; on the other hand, there was significant increased operation length, blood loss and systemic changes in BP or So2 in the ream group versus the unream group. CONCLUSIONS: We advocate that unream nailing in traumatic femoral shaft fractures is a simple, safe and effective procedure with significant advantages, especially in multitrauma patients.

Outcomes of pin and plaster versus locking plate in distal radius intraarticular fractures.

BACKGROUND: Distal radius fractures are among the most prevalent fractures predictive of probable occurrence of other osteoporotic fractures. They are treated via a variety of methods, but the best treatment has not been defined yet. OBJECTIVES: This study was performed to compare the results of open reduction and internal fixation with locking plates versus the pin and plaster method. MATERIALS AND METHODS: In this prospective study, 114 patients aged 40 to 60 years with Fernandez type III fracture referring to Imam-Reza and Mehr hospitals of Mashhad from 2009 to 2011, were selected randomly; after obtaining informed consent, they were treated with pin and plaster fixation (n = 57) or internal fixation with the volar locking plate (n = 57). They were compared at the one year follow up. Demographic features and standard radiographic indices were recorded and MAYO, DASH and SF - 36 tests were performed. Data was analyzed by SPSS software version 13, with descriptive indices, Mann-Whitney and Chi-square tests. RESULTS: SF-36 test demonstrated a better general health (P < 0.001), mental health (P = 0.006), physical functioning (P < 0.001), social functioning (P < 0.001) and energy/fatigue (P < 0.001) in LCP group. However, pain (P = 0.647) was not significantly different between the groups. Physical limitation (P < 0.001) and emotional limitation (P < 0.001) were greater in the pin and plaster group. Also, in the LCP group mean MAYO score (P < 0.001) was more than pin and plaster group. Mean DASH score was not different between the groups (P = 0.218). The rate of acceptable results of radiographic indices (P < 0.001), grip strength (P < 0.001) and range of motion in supination-pronation (P < 0.001) in LCP method were better than the pin and plaster method. CONCLUSIONS: In treatment of intra-articular distal radius fractures in middle-aged patients internal fixation with locking plates may be prefered to pin and plaster as the treatment of choice.

Posterior hip dislocation associated with posterior wall acetabular fracture and ipsilateral intertrochantric fracture: a very rare case report.

ABSTRACT: Traumatic hip dislocations are common in high-energy motor vehicle accidents. We present a case of a 43-year old man who sustained posterior hip dislocation with posterior wall acetabular fracture and ipsilateral intertrochantric fracture following a motorcycle accident. Urgent open reduction and internal fixation of the hip fracture-dislocation and fixation of intertrochantric fracture with a dynamic hip screw were done. To our knowledge, such an injury has been rarely reported in the literature. Possible mechanisms of injury and operative procedures are discussed. Radiographic follow-up after eight months showed union. No major complications were observed in our patient.

Migration of a broken steinman pin into the posterior compartment of the leg 12 years after total hip arthroplasty.

This report is on a migration of a Steinman pin into the posterior compartment of the calf. It was used to fix a greater trochanteric osteotomy in a total hip arthroplasty. The puzzling note is how this metal piece passed through the anterolateral compartment of the thigh to the posterior compartment of the calf. According to our literature review, migration of fixation pins through the knee joint is an extremely rare occurrence and could be missed by an inattentive physician.

The association between women's pelvic organ prolapse and joint hypermobility.

OBJECTIVE: To determine whether joint hypermobility is associated with pelvic organ prolapse. METHODS: The case-control study was conducted from January to April 2011 and comprised 30 women with pelvic organ prolapse, stage > or = II and 30 controls with stages 0 and I with similar age and parity. They were recruited from the gynaecology clinic at Imam Reza Hospital in Mashhad, Iran. The condition was evaluated by a quantification system and, for the purposes of this study, pelvic organ prolapse was defined as stage > or = II. All the subjects were examined in the dorsal lithotomic position with an empty bladder. A separate investigator evaluated each subject for joint hypermobility by using Beighton score which was calculated by doing five simple manoeuvres. SPSS 11.5 was used for data analysis. RESULTS: The mean age of the 30 cases was 35.40 +/- 6.39 years, while for the controls it was 35.36 +/- 5.9 years. Overall clinical joint hypermobility was found in 24 of the 60 (40%) subjects. There were no significant difference in the prevalence of joint hypermobility between the two groups. The prevalence of hypermobility in the cases was 36.7% (n = 11) versus 43.3% (n=13) in the controls (p = 0.59). The prevalence of cystocele in subjects with joint hypermobility was 41.7% (n = 10) versus 38.9% (n=14), (p < 0.83); rectocele 33.3% (n = 8) versus 41.7% ( n =15), (p < 0.73) women with normal joint mobility. No Significant differences were found between the groups with regard to other markers of connective tissue weakness such as the presence of varicose veins (p < 0.37), easy bruising ( p < 0.43) and observed striae ( p < 0.42). CONCLUSION: Joint hypermobility was not associated with pelvic organ prolapse in the study population. Further studies involving more patients with pelvic organ prolapse are recommended.

Safety evaluation of nanoliposomes containing cyclosporine a after ocular administration.

AIM: Cyclosporine A (CyA) is an anti inflammatory drug which modulates immune system. We prepared two liposomal formulations of CyA for ophthalmic administration. In the present study, the safety of these formulations was tested in rabbits. MATERIALS AND METHODS: Fusogenic and positively charged liposomes were prepared by solvent evaporation method. CyA concentration in ophthalmic preparations was 0.2% w/v. Twenty New Zealand albino rabbits (40 eyes) were divided into two groups. Right eyes were treated and left eyes served as control. Eyes were examined clinically in 1, 3, 7, 14 and 28th days of the study. Eleven eyes were enucleated for pathological evaluation at the end of the study. RESULTS: Mean size and charge of positively charged and fusogenic liposomes were 110.7 ± 1.5 and 114.9 ± 15.2 nm; 19.0 ± 2.2 and 2.5 ± 0.5 mV, respectively. Clinically, there were transient conjunctival injections and corneal epithelial defects in a few cases which were not limited to the treated eyes. Positively charged liposomes caused conjunctival injection in two cases, while this complication occurred in only one eye after administration of fusogenic liposomes. Histopathological examination revealed the presence of follicular conjunctivitis in two eyes with conjunctival injection. Inflammation in cases received the fusogenic form of the drug was mild and non-specific. CONCLUSIONS: The results of this study suggest that fusogenic liposomal preparation of CyA is safe and can be useful for future studies.