Natural resistance to cancer: A window of hope.

As healthcare systems are improving and thereby the life expectancy of human populations is increasing, cancer is representing itself as the second leading cause of death. Although cancer biologists have put enormous effort on cancer research so far, we still have a long way to go before being able to treat cancers efficiently. One interesting approach in cancer biology is to learn from natural resistance and/or predisposition to cancer. Cancer-resistant species and tissues are thought-provoking models whose study shed light on the inherent cancer resistance mechanisms that arose during the course of evolution. On the other hand, there are some syndromes and factors that increase the risk of cancer development, and revealing their underlying mechanisms will increase our knowledge about the process of cancer formation. Here, we review natural resistance and predisposition to cancer and the known mechanisms at play. Further insights from these natural phenomena will help design future cancer research and could ultimately lead to the development of novel cancer therapeutic strategies.

Elevated skull fractures: an institutional experience and individual participant data meta-analysis.

Elevated skull fracture (ESF) is a rare but potentially life-threatening type of skull fracture. The literature on this topic is relatively sparse. Herein, we conducted a meta-analysis of all the patients reported in the literature with ESFs with respect to their clinical management to better inform practice. On 20th of January 2023, we conducted a systematic search of literature to find all published cases of ESF. We also conducted a retrospective review of ESF cases from our institution. The data collection and analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After screening, 28 studies met the inclusion criteria. A total of 104 individual patients were included in the meta-analysis, with a median age of 24 years and 85.7% of whom were males. 11 patients (11.2%) had an unfavorable outcome while 37 (35.2%) had one or more complications. We found that GCS on admission is an independent predictor of poor outcome in ESF (odds ratio (95% confidence interval) = 1.605 (1.110-2.315), p value = 0.012). Regarding complications, dural injury (odds ratio (95% confidence interval) = 66.667 (7.407-500.00), p value < 0.001) and multiple bone involvement (odds ratio (95% confidence interval) = 6.849 (2.127-22.222), p value = 0.001) were independent predictors of complication. ESFs represent a rare yet consequential form of cranial injury, carrying potentially life-threatening implications if not promptly addressed. In this study, we present the meta-analysis of outcomes and complications within this patient cohort, offering a comprehensive synthesis of existing literature on this pathology. However, further investigation is imperative to provide higher-quality evidence and address lingering uncertainties in the classification and management of ESFs.

Outcomes of the early endoscopic-assisted suturectomy for treatment of multisuture craniosynostosis.

To present the outcomes and adverse events associated with the endoscopic-assisted, minimally invasive suturectomy in patients with multisuture synostosis. This retrospective cohort study included children < 65 days of age who underwent endoscopic-assisted suturectomy (EAS) for multisuture craniosynostosis at a single tertiary referral center from 2013 to 2021. The primary outcome was calvarial expansion, and the secondary outcome was adverse events. The pre- and post-operative 3-dimensional brain computed tomography (CT) scan was used to calculate the intracranial volume and cephalic index. During a period of 2 years, 10 infants (10-64 days) diagnosed with multisuture synostosis underwent single-stage EAS of every affected suture in our center. The coronal suture was the most prevalent involved suture among our cases. The mean age and weight of the patients were 39 ± 17.5 days and 4.39 ± 0.8 kg, respectively. The surgical procedure took 42 ± 17.4 min of time and caused 46 ± 25.4 mL of bleeding on average. Ninety percent of the operations were considered successful (n = 9) regarding calvarial expansion. There were two complications, one requiring an open vault surgery and one repairing a leptomeningeal cyst. In the eight patients who did not necessitate further interventions, the mean pre-operative intracranial volume was 643.3 ± 189.4 cm3. The follow-up results within the average of 38.9 months after surgery showed that as age increases, the intracranial volume also increased significantly (R: 0.6, P < 0.0001), which suggests continued skull growth in patients who underwent EAS. With the low rate of intra- or post-operative complications and promising results on revising the restricted skull sutures, EAS seems both a safe and effective therapeutic modality in patients with multisuture synostosis, especially if completed in the first months after birth.

Cerebral and pulmonary aspergillosis, treatment and diagnostic challenges of mixed breakthrough invasive fungal infections: case report study.

BACKGROUND: Breakthrough invasive fungal infections (bIFIs) are an area of concern in the scarcity of new antifungals. The mixed form of bIFIs is a rare phenomenon but could be potentially a troublesome challenge when caused by azole-resistant strains or non-Aspergillus fumigatus. To raise awareness and emphasize diagnostic challenges, we present a case of mixed bIFIs in a child with acute lymphoblastic leukemia. CASE PRESENTATION: A newly diagnosed 18-month-old boy with acute lymphoblastic leukemia was complicated with prolonged severe neutropenia after induction chemotherapy. He experienced repeated episodes of fever due to extended-spectrum beta-lactamase-producing Escherichia coli bloodstream infection and pulmonary invasive fungal infection with Aspergillus fumigatus (early-type bIFIs) while receiving antifungal prophylaxis. Shortly after pulmonary involvement, his condition aggravated by abnormal focal movement, loss of consciousness and seizure. Cerebral aspergillosis with Aspergillus niger diagnosed after brain tissue biopsy. The patient finally died despite 108-day antifungal therapy. CONCLUSIONS: Mixed bIFIs is a rare condition with high morbidity and mortality in the patients receiving immunosuppressants for hematological malignancies. This case highlights the clinical importance of Aspergillus identification at the species level in invasive fungal infections with multiple site involvement in the patients on antifungal prophylaxis.

MiR-21: A key player in glioblastoma pathogenesis.

Glioblastoma multiform (GBM) is one of common cancers worldwide which has high rate among various populations. Despite serious efforts worldwide, GBM remains a deadly disease which is associated with poor prognosis. Multiple lines evidence indicated that deregulation of a variety of cellular and molecular pathways are related with GBM pathogenesis. Among of various targets involved in GBM pathogenesis, microRNAs (miRNAs) have been emerged as targets which deregulation of them are related with various stages of GBM. These molecules are small non-coding RNAs which could affect on a variety of cellular and molecular pathways involved in GBM. It has been showed that deregulation of them are associated with initiation and progression of GBM. MiR-21 is one of important miRNAs involved in GBM pathogenesis. A large number studies indicated that this miRNA could affect on a variety of cellular and molecular pathways such as insulin-like growth factor (IGF)-binding protein-3 (IGFBP3), RECK, and TIMP3. Exosomes are one of important players in GBM pathogenesis. Among of various exosomes, exosomal miR-21 may has key roles in GBM pathogenesis. These findings indicated that miR-21 has critical roles in GBM pathogenesis and could be used as diagnostic and therapeutic biomarkers for GBM patients. Here, we summarized the roles of miR-21 and exosomal miR-21 in GBM pathogenesis. Moreover, we highlighted utilization of miR-21 as diagnostic and therapeutic biomarker for GBM patients.

A Novel Skin Incision for Posterior Fossa Midline and Paramedian Lesions: A Technical Note and Case Series.

Approaching posterior fossa pathologies is fairly challenging. Poor exposure, cerebrospinal fluid (CSF) leak following surgery, post-operative suboccipital and neck pain, as well as wound healing are all common complications following traditional suboccipital midline incision. Herein, we present a novel incision for approaching posterior fossa pathologies. The incision is shaped like a question mark and makes a musculofascial flap supplied by the occipital artery on top as well as a wide area for craniotomy. In our technique, the dura is also incised in a question mark-shaped manner. The new incision was used to operate on three patients who had masses in the posterior fossa. Following surgeries, none of the patients experienced any adverse events such as CSF leak, wound complications, severe suboccipital pain, and neck instability. This new incision not only facilitates approaching pathologies in the posterior fossa by providing wider exposure but also enables us to perform watertight dural closure, which reduces CSF leak. Furthermore, as the muscular incision provides a sufficient area for craniotomy, muscular retraction can be minimized to reduce post-operative pain. Moreover, unlike the midline avascular incision, the flap is well supplied by the occipital artery, which facilitates the healing procedure.

Surgical outcomes of myelomeningocele repair: A 20-year experience from a single center in a middle-income country.

BACKGROUND AND PURPOSE: Spina bifida is the second major cause of congenital disorders and the most common central nervous system congenital malformation compatible with life primarily. Herein, we describe the short-term outcome of post-natal Myelomeningocele (MMC) surgical management and predictors of its postoperative complications and mortality. METHODS: This retrospective chart review studies the children who underwent post-natal surgical management for MMC in Namazi hospital, a tertiary referral center, in southern Iran from May 2001 to September 2020. RESULTS: 248 patients were included in this study. The mean age at the operation was 8.47 ± 8.69 days. The most common site of involvement of MMC was Lumbosacral (86%, n = 204). At the evaluation conducted prior to the operation, cerebrospinal fluid leak was observed in 7% (n=16) of the patients. Postoperatively, 5.7% of the patients expired in the 30-day follow-up after the operation (n = 14), while 24% needed readmission (n = 47). The most common complications leading to readmission were wound dehiscence (n = 10, 42%) and wound purulence (n = 6, 25%). Only the site of the lesion (p-value = 0.035) was associated with postoperative complication. After controlling for potential confounders, the site of the lesion (adjusted odds ratio = 0.146, 95% confidence interval = 0.035-0.610, p-value = 0.008) and age at surgery (adjusted odds ratio = 1.048, 95% confidence interval = 1.002-1.096, p-value = 0.041) were significantly associated with mortality CONCLUSIONS: The age of the patients at the surgery and the site of the lesion are the two factors that were associated with mortality. However, further investigations into preoperative interventions and risk factors to mitigate the risk of complications and mortality are highly encouraged.

2- to 20-year myelomeningocele follow-up outcomes from a referral center in Southern Iran: the Shiraz experience.

BACKGROUND: The current convention for treatment of children with myelomeningocele (MMC) is timely surgical intervention combined with long-term follow-up by a multidisciplinary specialized team. This study aims to investigate the outcomes of MMC patients treated at Namazi Hospital. METHODS: All children presenting to Namazi Hospital with myelomeningocele between May 2001 and August 2020 were eligible for this study. For those with a documented telephone number, follow-up phone surveys with the patient's caregivers, on top of the review of the medical documents were carried out to assess mortality, morbidities, and the functional outcome of the care provided to them. RESULTS: A total of 125 patients were studied (62 females). All of the patients were followed up for a mean duration of 6.28 years (range 1-23 years). The majority were located in the lumbosacral area. All of the patients underwent postnatal surgical intervention for MMC in Namazi Hospital. Mean age at surgery was 9.51 days. There were statistically significant differences between urinary and bowel incontinence and presence of scoliosis, MMT grading of the lower limbs, school attendance, number of readmissions, and requirement of laminectomy at the initial surgical intervention. CONCLUSIONS: This study is the first to characterize the long-term outcomes of MMC patients in Iran. This study illustrates that there is a great need for improved access to and coordination of care in antenatal, perioperative, and long-term stages to improve morbidity and mortality.

Multiple intracranial dural arteriovenous fistula.

Dural arteriovenous fistula (DAVF) is also known as dural arteriovenous malformation. Two forms of DAVF have been introduced, however, here we present an exceptional case of DAVF with unique origin and drainage. In this study, we present a rare case of multiple DAVFs in a 50 year old man with right parietal intraparenchymal hemorrhage. MRI showed two round right parieto-occipital masses with flow void intensity adjacent to superior sagittal sinus (SSS). Another pathology connected to SSS by an abnormal cortical vein was detected anterior to first lesion. This study showed that both DAVFs were simultaneously drained in SSS in our patient.

Prognosis prediction in traumatic brain injury patients using machine learning algorithms.

Predicting treatment outcomes in traumatic brain injury (TBI) patients is challenging worldwide. The present study aimed to achieve the most accurate machine learning (ML) algorithms to predict the outcomes of TBI treatment by evaluating demographic features, laboratory data, imaging indices, and clinical features. We used data from 3347 patients admitted to a tertiary trauma centre in Iran from 2016 to 2021. After the exclusion of incomplete data, 1653 patients remained. We used ML algorithms such as random forest (RF) and decision tree (DT) with ten-fold cross-validation to develop the best prediction model. Our findings reveal that among different variables included in this study, the motor component of the Glasgow coma scale, the condition of pupils, and the condition of cisterns were the most reliable features for predicting in-hospital mortality, while the patients' age takes the place of cisterns condition when considering the long-term survival of TBI patients. Also, we found that the RF algorithm is the best model to predict the short-term mortality of TBI patients. However, the generalized linear model (GLM) algorithm showed the best performance (with an accuracy rate of 82.03 ± 2.34) in predicting the long-term survival of patients. Our results showed that using appropriate markers and with further development, ML has the potential to predict TBI patients' survival in the short- and long-term.

The Evolving Role of Next-Generation Sequencing in Pediatric Neurosurgery: A Call for Action for Research, Clinical Practice, and Optimization of Care.

Next-generation sequencing (NGS) is one of the most promising technologies that have truly revolutionized many aspects of clinical practice in recent years. It has been and is increasingly applied in many disciplines of medicine; however, it seems that pediatric neurosurgery despite its great potential has not truly embraced this new technology and is hesitant to use it in routine practice and guidelines. In this review, we summarize the developments that led to the establishment of NGS technology, review the applications and potentials of NGS in the disorders treated by pediatric neurosurgeons, and discuss the steps that we need to be taken to better harness NGS in pediatric neurosurgery.

Trigonocephaly: Quantitative Comparison of the Complete Vault Reconstruction and Minimally Invasive Suturectomy.

OBJECTIVE: The objective of the study was to present and compare outcomes and complications of conventional open reconstruction and minimally invasive correction of metopic synostosis in patients who underwent treatment of trigonocephaly in our center between 2015 and 2019. METHODS: The hospital database was searched for hospitalization and surgical information, as well as imaging of individuals with trigonocephaly. Postoperative evaluation of the patients was performed during the follow-up sessions. The radiological evaluation was based on brain computed tomography scans taken 2 years following the operation. RESULTS: Sixty-four patients (19 females and 45 males) had their trigonocephaly corrected surgically. Thirty-five patients (9 females and 26 males) had complete vault reconstruction surgery, while 29 patients (10 females and 19 males) had minimally invasive suturectomy (MIS). The postoperative cephalic width/intercoronal distance ratio and interpupillary distance/interfrontozygomatic distance ratio assessment showed no differences in the outcome of both groups (P value > 0.05). Minimally invasive techniques resulted in less intraoperative bleeding, a shorter stay in the intensive care unit and hospital, and a shorter surgery and anesthesia duration (P value < 0.05). CONCLUSIONS: Surgical treatment of trigonocephaly can result in a satisfactory correction of the deformity. MIS delivers a comparable result to complete vault reconstruction with less invasiveness and hospitalization and can be considered a reasonable option for patients in their early months of life. Patients must, however, undergo long-term cosmetic, behavioral, and developmental evaluations.

Prediction of 6 months endoscopic third ventriculostomy success rate in patients with hydrocephalus using a multi-layer perceptron network.

OBJECTIVE: Discrimination between patients most likely to benefit from endoscopic third ventriculostomy (ETV) and those at higher risk of failure is challenging. Compared to other standard models, we have tried to develop a prognostic multi-layer perceptron model based on potentially high-impact new variables for predicting the ETV success score (ETVSS). METHODS: Clinical and radiological data of 128 patients have been collected, and ETV outcomes were evaluated. The success of ETV was defined as remission of symptoms and not requiring VPS for six months after surgery. Several clinical and radiological features have been used to construct the model. Then the Binary Gravitational Search algorithm was applied to extract the best set of features. Finally, two models were created based on these features, multi-layer perceptron, and logistic regression. RESULTS: Eight variables have been selected (age, callosal angle, bifrontal angle, bicaudate index, subdural hygroma, temporal horn width, third ventricle width, frontal horn width). The neural network model was constructed upon the selected features. The result was AUC:0.913 and accuracy:0.859. Then the BGSA algorithm removed half of the features, and the remaining (Age, Temporal horn width, Bifrontal angle, Frontal horn width) were applied to construct models. The ANN could reach an accuracy of 0.84, AUC:0.858 and Positive Predictive Value (PPV): 0.92, which was higher than the logistic regression model (accuracy:0.80, AUC: 0.819, PPV: 0.89). CONCLUSION: The research findings have shown that the MLP model is more effective than the classic logistic regression tools in predicting ETV success rate. In this model, two newly added features, the width of the lateral ventricle's temporal horn and the lateral ventricle's frontal horn, yield a relatively high inter-observer reliability.

Chronic Kidney Disease in Isfahan Province, Action Plan for Screening in A Population-based Study.

INTRODUCTION: We intended to explore the prevalence of chronic kidney disease (CKD) and its different stages, as well as CKD associated variables in the adult population in Isfahan province, Iran. METHODS: Adults aged ≥ 18 were recruited in a cross-sectional study from 2017 to 2019. Data including demographics, anthropometrics, and laboratory findings were collected from each subject. The equation of chronic kidney disease- Epidemiology Collaboration (CKD-EPI) was used to estimate glomerular filtration rate (eGFR), and eGFR and UACR values were utilized to determine the stages of CKD. RESULTS: Data from a total of 3374 subjects was analyzed. The mean age of participants was 49.3 ± 14.09 years and 59.3% were female. The prevalence of CKD was 18.5%. Only 0.25 and 3.5% of the population were in CKD stage 3 and 4, while most of the patients were in CKD stage 2 (7.6%) and stage 1 (7.1%). CKD patients were mostly on refined grains diet and used lesser dairy products compared to healthy participants. Variables including systolic blood pressure (OR = 1.018; P < .001), diastolic blood pressure (OR = 1.005; P < .05), fasting blood sugar (OR = 1.011; P < .001), female sex (OR = 1.319; P < .05), body mass index (OR = 1.030; P < .05), married status (OR = 1.335; P < .05), and smoking (OR = 1.529; P < .05) were significantly associated with increased risk of CKD in the logistic regression analysis. CONCLUSION: According to our results, the prevalence of CKD, especially stages 1 and 2, is quite high in central part of Iran. These findings help us to improve the screening for CKD patients and perform larger scale studies to identify the challenges ahead.  DOI: 10.52547/ijkd.7201.

Association between N142D genetic polymorphism of GSTO2 and susceptibility to colorectal cancer.

Expression pattern analysis has been revealed that glutathione S-transferase omega 2 (GSTO2, a member of class omega) is ubiquitously expressed. Over expression of GSTO2 induced apoptosis. The gene encoding GSTO2 was localized to human chromosome 10q24.3, a region that may harbor gene(s) involved in the developing of colorectal cancer. To investigate the association between GSTO2 N142D genetic polymorphism and susceptibility to colorectal cancer the present study was done. We studied 63 (26 females, 37 males) colorectal cancer patients and 126 (52 females, 74 males) healthy individuals. The control subjects were frequency matched for age and gender with the colorectal cancer group. The genotypes were performed using RFLP-PCR method. The ND and DD genotypes were not associated with risk of colorectal cancer, in comparison with the NN genotype. Family history for cancer in the first degree of relatives significantly differed between cases and controls (P = 0.012). The profiles of GSTO2 genotypes and family history in control and cancerous groups were compared to each other. Subjects with NN genotype and positive family history significantly were at high risk to develop colorectal cancer in comparison with subjects with DD or ND genotypes and negative family history (P = 0.003). Present findings indicating that GSTO2 NN genotype increase the risk of colorectal cancer in persons with positive family history for cancer in the first degree relatives.

Probabilistic nucleation governs time, amount, and location of mineral precipitation and geometry evolution in the porous medium.

One important unresolved question in reactive transport is how pore-scale processes can be upscaled and how predictions can be made on the mutual effect of chemical processes and fluid flow in the porous medium. It is paramount to predict the location of mineral precipitation besides their amount for understanding the fate of transport properties. However, current models and simulation approaches fail to predict precisely where crystals will nucleate and grow in the spatiotemporal domain. We present a new mathematical model for probabilistic mineral nucleation and precipitation. A Lattice Boltzmann implementation of the two-dimensional mineral surface was developed to evaluate geometry evolution when probabilistic nucleation criterion is incorporated. To provide high-resolution surface information on mineral precipitation, growth, and distribution, we conducted a total of 27 calcium carbonate synthesis experiments in the laboratory. The results indicate that nucleation events as precursors determine the location and timing of crystal precipitation. It is shown that reaction rate has primary control over covering the substrate with nuclei and, subsequently, solid-phase accumulation. The work provides insight into the spatiotemporal evolution of porous media by suggesting probabilistic and deterministic domains for studying reactive transport processes. We indicate in which length- and time-scales it is essential to incorporate probabilistic nucleation for valid predictions.

Probabilistic Nucleation and Crystal Growth in Porous Medium: New Insights from Calcium Carbonate Precipitation on Primary and Secondary Substrates.

Knowledge of crystal nucleation and growth is paramount in understanding the geometry evolution of porous medium during reactive transport processes in geo-environmental studies. To predict transport properties precisely, it is necessary to delineate both the amount and location of nucleation and precipitation events in the spatiotemporal domain. This study investigates the precipitation of calcium carbonate crystals on a heterogeneous sandstone substrate as a function of chemical supersaturation, temperature, and time. The main objective was to evaluate solid formation under different boundary conditions when the solid-liquid interface plays a key role. New observations were made on the effect of primary and secondary substrates and the role of preferential precipitation locations on the rock surfaces. The results indicate that supersaturation and temperature determine the amount, distribution pattern, and growth rate of crystals. Substrate characteristics governed the nucleation, growth location, and evolution probability across time and space. Moreover, substrate surface properties introduced preferential sites that were occupied and covered with solids first. Our results highlight the complex dynamics induced by substrate surface properties on the spatial and temporal solute distribution, transport, and deposition. We accentuate the great potentials of the probabilistic nucleation model to describe mineral formation in a porous medium during reactive transport.

Predictive Factors for Postoperative Tracheostomy Requirement in Children Undergoing Surgical Resection of Medulloblastoma.

OBJECTIVE: This study is aimed at identifying factors predicting tracheostomy requirement in children diagnosed with a posterior fossa medulloblastoma postoperatively. METHODS: A retrospective chart review of all patients younger than 18 undergoing medulloblastoma resection from 2012 to 2020 at Namazi Hospital was conducted. RESULTS: Forty-five patients (26%) needed tracheostomy after the operation. The most common correlates were brainstem compression and absence of gag reflex before operation. Patients who had brainstem compression and infiltration by medulloblastoma, bilateral absence of gag reflex before operation, subtotal resection of the tumor, and postoperative brainstem contusion were more likely to require tracheostomy. No statistically significant difference was observed between males and females and different ages. CONCLUSIONS: Medulloblastoma is the most common pediatric malignancy. Postoperative ventilator dependency is an important complication in postoperative recovery of patients undergoing medulloblastoma resection. Considering the mutism syndrome with all its question marks by means of predisposing factors, we dealt with a 2-week policy whether there would be any clinical resolution regarding patients' gag reflex. The results show that if we aim for total tumor resection, tracheostomy that is a highly costly and stressful postoperative morbidity can be prevented.