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Pathological Conditions, Signs and Symptoms - Top 30 Publications

Tuberculosis Infectiousness and Host Susceptibility.

The transmission of tuberculosis is complex. Necessary factors include a source case with respiratory disease that has developed sufficiently for Mycobacterium tuberculosis to be present in the airways. Viable bacilli must then be released as an aerosol via the respiratory tract of the source case. This is presumed to occur predominantly by coughing but may also happen by other means. Airborne bacilli must be capable of surviving in the external environment before inhalation into a new potential host-steps influenced by ambient conditions and crowding and by M. tuberculosis itself. Innate and adaptive host defenses will then influence whether new infection results; a process that is difficult to study owing to a paucity of animal models and an inability to measure infection directly. This review offers an overview of these steps and highlights the many gaps in knowledge that remain.

What Is the Risk of Anastomotic Leak After Repeat Intestinal Resection in Patients With Crohn's Disease?

Approximately half of Crohn's patients require intestinal resection, and many need repeat resections.

A Randomized Control Trial of Preoperative Oral Antibiotics as Adjunct Therapy to Systemic Antibiotics for Preventing Surgical Site Infection in Clean Contaminated, Contaminated, and Dirty Type of Colorectal Surgeries.

Preoperative bowel preparation with or without oral antibiotics is controversial in terms of postoperative surgical site infections.

Nodal Disease in Rectal Cancer Patients With Complete Tumor Response After Neoadjuvant Chemoradiation: Danger Below Calm Waters.

A subset of patients with rectal cancer who undergo neoadjuvant chemoradiation therapy will develop a complete pathologic tumor response. Complete nodal response is not universal in these patients and is difficult to assess clinically. Quantifying the risk of nodal disease would allow for targeted therapy with either radical resection or "watchful waiting."

Genetic variants of SULT1A1 and XRCC1 genes and risk of lung cancer in Bangladeshi population.

Lung cancer is one of the most frequently occurring cancers throughout the world as well as in Bangladesh. This study aimed to correlate the prognostic and/or predictive value of functional polymorphisms in SULT1A1 (rs9282861) and XRCC1 (rs25487) genes and lung cancer risk in Bangladeshi population. A case-control study was conducted which comprises 202 lung cancer patients and 242 healthy volunteers taking into account the age, sex, and smoking status. After isolation of genomic DNA, genotyping was done by polymerase chain reaction-restriction fragment length polymorphism method and the lung cancer risk was evaluated as odds ratio that was adjusted for age, sex, and smoking status. A significant association was found between SULT1A1 rs9282861 and XRCC1 rs25487 polymorphisms and lung cancer risk. In case of rs9282861 polymorphism, Arg/His (adjusted odds ratio = 5.06, 95% confidence interval = 3.05-8.41, p < 0.05) and His/His (adjusted odds ratio = 3.88, 95% confidence interval = 2.20-6.82, p < 0.05) genotypes were strongly associated with increased risk of lung cancer in comparison to the Arg/Arg genotype. In case of rs25487 polymorphism, Arg/Gln heterozygote (adjusted odds ratio = 4.57, 95% confidence interval = 2.79-7.46, p < 0.05) and Gln/Gln mutant homozygote (adjusted odds ratio = 4.99, 95% confidence interval = 2.66-9.36, p < 0.05) were also found to be significantly associated with increased risk of lung cancer. This study demonstrates that the presence of His allele and Gln allele in case of SULT1A1 rs9282861 and XRCC1 rs25487, respectively, involve in lung cancer prognosis in Bangladeshi population.

Cell-free DNA levels and correlation to stage and outcome following treatment of locally advanced rectal cancer.

Accurate staging of rectal cancer remains essential for optimal patient selection for combined modality treatment, including radiotherapy, chemotherapy and surgery. We aimed at examining the correlation of cell free DNA with the pathologic stage and subsequent risk of recurrence for patients with locally advanced rectal cancer undergoing preoperative chemoradiation. We examined 75 patients with locally advanced rectal cancer receiving preoperative chemoradiation. Blood samples for translational use were drawn prior to rectal surgery. The level of cell free DNA was quantified by digital droplet PCR and expressed as copy number of beta 2 microglobulin. We found a median level of cell free DNA in the AJCC stages I-III of 3100, 8300, and 10,700 copies/mL respectively. For patients with 12 sampled lymph nodes or above, the median level of cell free DNA were 2400 copies/mL and 4400 copies/mL (p = 0.04) for node negative and node positive disease respectively. The median follow-up was 39 months and 11 recurrences were detected (15%). The median level for patients with recurrent disease was 13,000 copies/mL compared to 5200 copies/mL for non-recurrent patients (p = 0.08). We have demonstrated a correlation between the level of total cell free DNA and the pathologic stage and nodal involvement. Furthermore, we have found a trend towards a correlation with the risk of recurrence following resection of localized rectal cancer.

Insulin resistance and reduced metabolic flexibility: cause or consequence of NAFLD?

Whether non-alcoholic fatty liver disease (NAFLD) precedes insulin resistance (IR) or IR preludes/causes NAFLD has been long debated. Recent studies have shown that there are two phenotypes of NAFLD, 'genetic' vs 'metabolic' NAFLD. The former patients are more at risk of hepatocellular carcinoma and chronic liver disease the latter are more IR and at increased risk of type 2 diabetes (T2D). Even if they are not yet diabetics, from a metabolic point of view having NAFLD is equivalent to T2D with reduced peripheral glucose disposal and impaired suppression of hepatic glucose production, but without fasting hyperglycaemia. T2D develops only when hepatic autoregulation is lost and glucose production exceeds the capacity of muscle glucose disposal.In NAFLD adipocytes are resistant to the effect of insulin, lipolysis is increased and excess plasma free fatty acids (FFA) are taken up by other organs (mainly liver) where they are stored as lipid droplets or oxidized. Increased adiposity is associated with worsen severity of both 'genetic' and 'metabolic' NAFLD. FFA oxidative metabolism is increased in NAFLD and not shifted towards glucose during insulin infusion. Although this reduced metabolic flexibility is an early predictor of T2D, it can be seen also as a protective mechanism against excess FFA.In conclusion, IR precedes and causes 'metabolic' NAFLD, but not 'genetic' NAFLD. Reduced metabolic flexibility in NAFLD might be seen as a protective mechanism against FFA overflow, but together with IR remains a strong risk factor for T2D that develops with the worsening of hepatic regulation of glucose production.

Inflammation-regulated mRNA stability and the progression of vascular inflammatory diseases.

Cardiovascular disease remains a major medical and socioeconomic burden in developed and developing societies, and will increase with an aging and increasingly sedentary society. Vascular disease and atherosclerotic vascular syndromes are essentially inflammatory disorders, and transcriptional and post-transcriptional processes play essential roles in the ability of resident vascular and inflammatory cells to adapt to environmental stimuli. The regulation of mRNA translocation, stability, and translation are key processes of post-transcriptional regulation that permit these cells to rapidly respond to inflammatory stimuli. For the most part, these processes are controlled by elements in the 3'-UTR of labile, proinflammatory transcripts. Since proinflammatory transcripts almost exclusively contain AU-rich elements (AREs), this represents a tightly regulated and specific mechanism for initiation and maintenance of the proinflammatory phenotype. RNA-binding proteins (RBPs) recognize cis elements in 3'-UTR, and regulate each of these processes, but there is little literature exploring the concept that RBPs themselves can be directly regulated by inflammatory stimuli. Conceptually, inflammation-responsive RBPs represent an attractive target of rational therapies to combat vascular inflammatory syndromes. Herein we briefly describe the cellular and molecular etiology of atherosclerosis, and summarize our current understanding of RBPs and their specific roles in regulation of inflammatory mRNA stability. We also detail RBPs as targets of current anti-inflammatory modalities and how this may translate into better treatment for vascular inflammatory diseases.

Atrioesophageal Fistula: Clinical Presentation, Procedural Characteristics, Diagnostic Investigations, and Treatment Outcomes.

Percutaneous or surgical ablation are increasingly used worldwide in the management of atrial fibrillation. The development of atrioesophageal fistula (AEF) is among the most serious and lethal complications of atrial fibrillation ablation. We sought to characterize the clinical presentation, procedural characteristics, diagnostic investigations, and treatment outcomes of all reported cases of AEF.

Managing Cancer Relapse After Radical Prostatectomy: Adjuvant Versus Salvage Radiation Therapy.

An increasing proportion of men are undergoing radical prostatectomy for locally advanced prostate cancer. More than half of men with adverse pathologic features are expected to experience disease recurrence within 10 years. This article discusses the use of postoperative radiation therapy to decrease this risk. Evidence from 3 randomized trials and multiple retrospective studies indicates that either adjuvant or salvage radiation improve biochemical progression-free survival and may improve overall survival. Novel imaging and genomic analysis can improve patient selection for either modality, however current tests are unable to identify all patients who may benefit from additional local therapy.

Mutations in GPAA1, Encoding a GPI Transamidase Complex Protein, Cause Developmental Delay, Epilepsy, Cerebellar Atrophy, and Osteopenia.

Approximately one in every 200 mammalian proteins is anchored to the cell membrane through a glycosylphosphatidylinositol (GPI) anchor. These proteins play important roles notably in neurological development and function. To date, more than 20 genes have been implicated in the biogenesis of GPI-anchored proteins. GPAA1 (glycosylphosphatidylinositol anchor attachment 1) is an essential component of the transamidase complex along with PIGK, PIGS, PIGT, and PIGU (phosphatidylinositol-glycan biosynthesis classes K, S, T, and U, respectively). This complex orchestrates the attachment of the GPI anchor to the C terminus of precursor proteins in the endoplasmic reticulum. Here, we report bi-allelic mutations in GPAA1 in ten individuals from five families. Using whole-exome sequencing, we identified two frameshift mutations (c.981_993del [p.Gln327Hisfs(∗)102] and c.920delG [p.Gly307Alafs(∗)11]), one intronic splicing mutation (c.1164+5C>T), and six missense mutations (c.152C>T [p.Ser51Leu], c.160_161delinsAA [p.Ala54Asn], c.527G>C [p.Trp176Ser], c.869T>C [p.Leu290Pro], c.872T>C [p.Leu291Pro], and c.1165G>C [p.Ala389Pro]). Most individuals presented with global developmental delay, hypotonia, early-onset seizures, cerebellar atrophy, and osteopenia. The splicing mutation was found to decrease GPAA1 mRNA. Moreover, flow-cytometry analysis of five available individual samples showed that several GPI-anchored proteins had decreased cell-surface abundance in leukocytes (FLAER, CD16, and CD59) or fibroblasts (CD73 and CD109). Transduction of fibroblasts with a lentivirus encoding the wild-type protein partially rescued the deficiency of GPI-anchored proteins. These findings highlight the role of the transamidase complex in the development and function of the cerebellum and the skeletal system.

De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability.

Calcium/calmodulin-dependent protein kinase II (CAMK2) is one of the first proteins shown to be essential for normal learning and synaptic plasticity in mice, but its requirement for human brain development has not yet been established. Through a multi-center collaborative study based on a whole-exome sequencing approach, we identified 19 exceedingly rare de novo CAMK2A or CAMK2B variants in 24 unrelated individuals with intellectual disability. Variants were assessed for their effect on CAMK2 function and on neuronal migration. For both CAMK2A and CAMK2B, we identified mutations that decreased or increased CAMK2 auto-phosphorylation at Thr286/Thr287. We further found that all mutations affecting auto-phosphorylation also affected neuronal migration, highlighting the importance of tightly regulated CAMK2 auto-phosphorylation in neuronal function and neurodevelopment. Our data establish the importance of CAMK2A and CAMK2B and their auto-phosphorylation in human brain function and expand the phenotypic spectrum of the disorders caused by variants in key players of the glutamatergic signaling pathway.

Local Genetic Correlation Gives Insights into the Shared Genetic Architecture of Complex Traits.

Although genetic correlations between complex traits provide valuable insights into epidemiological and etiological studies, a precise quantification of which genomic regions disproportionately contribute to the genome-wide correlation is currently lacking. Here, we introduce ρ-HESS, a technique to quantify the correlation between pairs of traits due to genetic variation at a small region in the genome. Our approach requires GWAS summary data only and makes no distributional assumption on the causal variant effect sizes while accounting for linkage disequilibrium (LD) and overlapping GWAS samples. We analyzed large-scale GWAS summary data across 36 quantitative traits, and identified 25 genomic regions that contribute significantly to the genetic correlation among these traits. Notably, we find 6 genomic regions that contribute to the genetic correlation of 10 pairs of traits that show negligible genome-wide correlation, further showcasing the power of local genetic correlation analyses. Finally, we report the distribution of local genetic correlations across the genome for 55 pairs of traits that show putative causal relationships.

Obesity Often Overstated But Hardly Understood.

Localized Optogenetic Targeting of Rotors in Atrial Cardiomyocyte Monolayers.

Recently, a new ablation strategy for atrial fibrillation has emerged, which involves the identification of rotors (ie, local drivers) followed by the localized targeting of their core region by ablation. However, this concept has been subject to debate because the mode of arrhythmia termination remains poorly understood, as dedicated models and research tools are lacking. We took a unique optogenetic approach to induce and locally target a rotor in atrial monolayers.

Choice of implant combinations in total hip replacement: systematic review and network meta-analysis.

Objective To compare the survival of different implant combinations for primary total hip replacement (THR). Design Systematic review and network meta-analysis. Data sources Medline, Embase, The Cochrane Library,, WHO International Clinical Trials Registry Platform, and the EU Clinical Trials Register.Review methods Published randomised controlled trials comparing different implant combinations. Implant combinations were defined by bearing surface materials (metal-on-polyethylene, ceramic-on-polyethylene, ceramic-on-ceramic, or metal-on-metal), head size (large ≥36 mm or small <36 mm), and fixation technique (cemented, uncemented, hybrid, or reverse hybrid). Our reference implant combination was metal-on-polyethylene (not highly cross linked), small head, and cemented. The primary outcome was revision surgery at 0-2 years and 2-10 years after primary THR. The secondary outcome was the Harris hip score reported by clinicians.Results 77 studies were included in the systematic review, and 15 studies (3177 hips) in the network meta-analysis for revision. There was no evidence that the risk of revision surgery was reduced by other implant combinations compared with the reference implant combination. Although estimates are imprecise, metal-on-metal, small head, cemented implants (hazard ratio 4.4, 95% credible interval 1.6 to 16.6) and resurfacing (12.1, 2.1 to 120.3) increase the risk of revision at 0-2 years after primary THR compared with the reference implant combination. Similar results were observed for the 2-10 years period. 31 studies (2888 patients) were included in the analysis of Harris hip score. No implant combination had a better score than the reference implant combination.Conclusions Newer implant combinations were not found to be better than the reference implant combination (metal-on-polyethylene (not highly cross linked), small head, cemented) in terms of risk of revision surgery or Harris hip score. Metal-on-metal, small head, cemented implants and resurfacing increased the risk of revision surgery compared with the reference implant combination. The results were consistent with observational evidence and were replicated in sensitivity analysis but were limited by poor reporting across studies.Systematic review registration PROSPERO CRD42015019435.

Sex-Related Differences in Vasomotor Function in Patients With Angina and Unobstructed Coronary Arteries.

Coronary vasomotor dysfunction is an important mechanism for angina in patients with unobstructed coronary arteries.

Harmful Algal Bloom-Associated Illnesses in Humans and Dogs Identified Through a Pilot Surveillance System - New York, 2015.

Cyanobacteria, also known as blue-green algae, are photosynthetic, aquatic organisms found in fresh, brackish, and marine water around the world (1). Rapid proliferation and accumulation of potentially toxin-producing cyanobacteria characterize one type of harmful algal bloom (HAB). HABs have the potential to cause illness in humans and animals (2,3); however, the epidemiology of these illnesses has not been well characterized. Statewide in 2015, a total of 139 HABs were identified in New York, 97 (70%) of which were confirmed through laboratory analysis; 77 independent beach closures were ordered at 37 beaches on 20 different bodies of water. To better characterize HAB-associated illnesses, during June-September 2015, the New York State Department of Health (NYSDOH) implemented a pilot surveillance system in 16 New York counties. Activities included the collection of data from environmental HAB reports, illness reports, poison control centers, and syndromic surveillance, and increased outreach to the public, health care providers, and veterinarians. During June-September, 51 HAB-associated illnesses were reported, including 35 that met the CDC case definitions*; 32 of the cases occurred in humans and three in dogs. In previous years, New York never had more than 10 HAB-associated illnesses reported statewide. The pilot surveillance results from 16 counties during a 4-month period suggest that HAB-associated illnesses might be more common than previously reported.

Addressing Obesity Must Go Beyond Advising Patients to Eat Healthy and Exercise.

A high-throughput in vivo screening method in the mouse for identifying regulators of metastatic colonization.

We describe a sensitive, robust, high-throughput method for quantifying the ability of metastatic tumor cells to colonize a secondary organ. Metastasis is the leading cause of death in cancer patients, and successful colonization of the secondary organ is the rate-limiting step in the metastatic process; thus, experimental methods that can be used to interrogate the key factors required for this critical step are of great importance. The experimental metastasis assay we detail here includes tail-vein injection of cancer cells into the mouse and determination of the resulting secondary organ colonization, primarily in the lung, 10 d post dosing. This assay can be used to investigate factors that regulate metastatic colonization both at the tumor-cell-intrinsic level (via manipulation of the tumor cells before injection) and at the tumor-cell-extrinsic level (such as the tissue microenvironment, via the use of genetically modified (GM) mice or agents such as antibodies or drugs). Using this method, we have robustly screened more than 950 GM mouse lines to identify novel microenvironmental regulators of metastatic colonization. The experimental details discussed here include choosing of appropriate cell numbers, handling of the cells, selection of recipient animals and injection techniques. Furthermore, we discuss key experimental design considerations, including the choice of the method used to determine metastatic burden and statistical analysis of the results, as well as provide troubleshooting tips and identification of factors that contribute to experimental variability.

Transient sick sinus syndrome with complete atrioventricular block associated with ergonovine intake: A case report.

More mature or older women are more likely to undergo in vitro fertilization and embryo implant. These women have a greater chance of receiving ergonovine therapy because of a suspected abortion. We present this case report to call attention to a latent lethal adverse effect in everyday obstetric practice using ergonovine. It requires more attention and close monitoring PATIENT CONCERNS:: We presented the case of a 38-year-old female patient with general weakness and mild chest tightness after ergonovine use.

Sonography used in the infantile desmoid fibromatosis of postcricoid area: A case report.

Infantile desmoid fibromatosis of the postcricoid area is a rare disease and is characterized by a proliferation of fibrous tissue with non-metastasis, local infiltration, and a high rate of recurrence after surgical resection. Currently, ultrasound is scarcely used in the hypopharynx and larynx area.

Umbilical cord mesenchyme stem cell local intramuscular injection for treatment of uterine niche: Protocol for a prospective, randomized, double-blinded, placebo-controlled clinical trial.

Uterine niche is defined as a triangular anechoic structure at the site of the scar or a gap in the myometrium at the site of a previous caesarean section. The main clinical manifestations are postmenstrual spotting and intrauterine infection, which may seriously affect the daily life of nonpregnant women. Trials have shown an excellent safety and efficacy for the potential of mesenchymal stem cells (MSCs) as a therapeutic option for scar reconstruction. Therefore, this study is designed to investigate the safety and efficacy of using MSCs in the treatment for the uterine niche.

Spontaneous spinal epidural hematomas: One case report and rehabilitation outcome.

Spontaneous spinal epidural hematoma (SSEH) is a relatively rare but potentially disabling disease, and the classical presentation of it includes an acute onset of severe, sometimes radiating back or neck pain, followed by signs and symptoms of rapidly evolving nerve root or spinal cord compression.

Rare esophageal ulcers related to Behçet disease: A case report.

The fundamental pathogenesis of Behçet disease (BD) is still unclear and controversial. Many cases of oral aphthous ulcers and genital ulcers related to BD are reported; nevertheless, idiopathic giant esophageal ulcers related to BD are rare. A rare case for esophageal ulcers related to BD is presented.

Sudden onset of static equilibrium dysfunction in patients receiving a cochlear implant.

We investigated the sudden onset of static equilibrium dysfunction caused by cochlear implantation (CI) in congenital hearing loss patients.

The pancreatic juice length in the stent tube as the predicting factor of clinical relevant postoperative pancreatic fistula after pancreaticoduodenectomy.

Several risk factors for pancreatic fistula had been widely reported, but there was no research focusing on the exocrine output of remnant gland.During the study period of January 2015 to September 2016, 82 patients accepted pancreaticoduodenectomy (PD, end-to-end dunking pancreaticojejunostomy with internal stent tube). All the data were collected, including preoperative medical status, operative course, final pathology, gland texture, pancreatic duct diameter, size of the stent, length of pancreatic juice in the stent tube, width of the pancreatic stump, diameter of the jejunum and the status of postoperative pancreatic fistula (POPF). POPF was defined according to International Study Group of Pancreatic Fistula criteria.The diameter of pancreatic duct in the POPF group was significantly smaller than that in the group without POPF (1.99 vs 2.90 mm, P = .000). The length of pancreatic juice in the stent tube in the POPF group was significantly longer than that in the group without POPF (18.04 vs 6.92 cm, P = .014). There were more pancreatic ductal adenocarcinoma cases and hard glands in the group without POPF. The length of pancreatic juice in the clinically relevant postoperative pancreatic fistula (CR-POPF) group was significantly longer than that in the grade A group (32.4 vs 9.21 cm, P = .000). Multivariate analysis identified gland texture and length of pancreatic juice as independent predictors for pancreatic fistula. Multivariate analysis also identified the length of pancreatic juice as an independent predictor for CR-POPF.The length of pancreatic juice in the stent tube might be a useful predictive factor of POPF after PD, especially for CR-POPF.

Severe enteropathy with villous atrophy in prolonged mefenamic acid users - a currently under-recognized in previously well-recognized complication: Case report and review of literature.

Mefenamic acid-induced enteropathy may be an under-recognized condition because few reported cases and no review of literature to comprehensively describe all reported cases exist. From inception until February 2017, a systematic literature search identified twenty original reports of cases of mefenamic acid-induced enteropathy. Additional five cases were identified at our hospital. All cases were included in the analyses.

Clinical predictors of outcomes in patients undergoing emergency air medical transport from Kinmen to Taiwan.

Emergency air medical transport (EAMT) is indispensable for acutely or critically ill patients in remote areas. We determined patient-level and transport-specific factors associated with all-cause mortality after EAMT.We conducted a population-based, retrospective cohort study using a prospective registry consisting of clinical/medical records. Study inclusion criteria consisted of all adults undergoing EAMT from Kinmen hospital to the ED of Taipei Veterans General Hospital (TVGH) between January 1, 2006 and December 31, 2012. The primary outcome assessments were 7-day and 30-day mortality.A total of 370 patients transported to TVGH were enrolled in the study with a mean age of 54.5 ± 21.5 (SD) years and with a male predominance (71.6%). The average in-transit time was 1.4 ± 0.4 hours. The 7-day, 30-day, and in-hospital mortality rates were 10.3%, 14.1%, and 14.9%. Among them 33.5% (124/370) were categorized under neurological etiologies, whereas 24.9% (90/370) cardiovascular, followed by 16.2% (60/370) trauma patients. Independent predictors associated with 7-day all-cause mortality were age (odds ratio [OR] 1.043, 95% confidence interval [CI] 1.016-1.070), Glasgow Coma Scale (GCS) (OR 0.730, 95% CI 0.650-0.821), and hematocrit level (OR 0.930, 95% CI 0.878-0.985). Independent predictors associated with 30-day all-cause mortality were age (OR 1.028, 95% CI 1.007-1.049), GCS (OR 0.686, 95% CI 0.600-0.785), hematocrit (OR 0.940, 95% CI 0.895-0.988), hemodynamic instability (OR 5.088 95% CI 1.769-14.635), and endotracheal intubation (OR 0.131 95% CI 0.030-0.569). The 7-day and 30-day mortality were not significantly related to transport-specific factors, such as length of flight, type of paramedic crew on board, or day and season of transport. Clinical patient-level factors, as opposed to transport-level factors, were associated with 7- and 30-day all-cause mortality in patients undergoing interfacility EAMT from Kinmen to Taiwan.

Skull metastases detecting on arterial spin labeling perfusion: Three case reports and review of literature.

Detection of skull metastases is as important as detection of brain metastases because early diagnosis of skull metastases is a crucial determinant of treatment. However, the skull can be a blind spot for assessing metastases on routine brain magnetic resonance imaging (MRI). To the best of our knowledge, the finding of skull metastases on arterial spin labeling (ASL) has not been reported. ASL is a specific MRI sequence for evaluating cerebral blood flow using magnetized endogenous inflow blood. This study uses ASL as a routine sequence of brain MRI protocol and describes 3 clinical cases of skull metastases identified by ASL. The study also highlights the clinical usefulness of ASL in detecting skull metastases.