In any case, these results should be taken with caution, as the role of a given Deinococcus-Thermus, which is associated with the production of carotenoids with antioxidant, anti-apoptotic, and anti-inflammatory properties, was increased in the TG (p = 0.032). Prevotellaceae, Lachnospiraceae, Peptostreptococcaceae, Peptococcaceae, and Terrisporobacter were increased in the TG. Members of these families have the ability to ferment complex dietary polysaccharides and produce larger amounts of short chain fatty acids. Regarding species, only Clostridium butyricum was increased in the TG (p = 0.048). Clostridium butyricum is well-known as probiotic in humans, but it has also been associated with overall positive gut effects  in weanling pigs. Although the use of PSB did not modify the overall richness of microbiota composition of these slaughter pigs, it may have increased specific taxa associated with better gut health parameters.The study assessed changes in the gut microbiota of pigs after dietary supplementation with protected sodium butyrate (PSB) during the growing-fattening period (≈90 days). One gram of colon content from 18 pigs (9 from the treatment group -TG- and 9 from the control group -CG-) was collected. Bacterial DNA was extracted and 16S rRNA high-throughput amplicon sequencing used to assess microbiota changes between groups. The groups shared 75.4% of the 4697 operational taxonomic units identified. No differences in alpha diversity were found, but significant differences for some specific taxa were detected between groups. The low-represented phylum  The study and implications of gut microbiota on pig health has been the objective of many recent studies, and an overall correlation between microbiota and health has been observed ,2,3. GutFirmicutes and Bacteroidetes phyla, which are the predominant bacteria in healthy pigs (85% to 90% of the population). Other important but less frequent phyla are Proteobacteria, which includes the Enterobacteriaceae family, Actinobacteria, Spirochaetes, and Verrucomicrobia.The intestinal microbiota is a non-static, complex structure that can be easily altered by many factors . Animal Clostridium, Lactobacillus, Lactococcus, Streptococcus, Blautia, Ruminococcus, Roseburia, and Enterococcus (Firmicutes), and Bacteroides and Prevotella (Bacteroidetes), suggesting a core microbiota for healthy commercial swine [Bacteroidetes (genus Prevotella), Firmicutes , Proteobacteria  have been associated with diarrhea in the first weeks of piglets’ life [Among the major genera within these two main phyla would be al swine ,10. Relats’ life ,13,14,15ts’ life . These vSalmonella or enterotoxigenic E. coli. Several effects have been associated with the administration of OA that would promote intestinal health. For instance, OA, such as butyric acid, are the preferred energy substrate for colon cells, promoting their normal proliferation and differentiation [Organic acids (OA) are being used as an alternative to antibiotics in pigs for the control of digestive disorders caused by enteric pathogens such as ntiation . It alsontiation . OA seemntiation .Salmonella. In addition, OA would enter the pathogenic bacteria cell in their non-dissociated form and decrease the intracellular pH when dissociating, thus disrupting DNA synthesis [However, medium chain fatty acids, such as lauric acid or sodium heptanoate, and short chain fatty acids, such as formic or butyric acid, may also positively modify microbiota composition ,21,22. Tynthesis ,25. Altoynthesis .Most of the studies on the effects of OA on the modification of the intestinal microbiota in swine have been carried out in young pigs, i.e., suckling and/or weaned piglets, and after administration of OA for a limited period of time. However, few studies have focused on older pigs or after long treatments. Thus, the aim of this study was to assess changes in the gut microbiota of healthy fattening pigs after dietary supplementation with a formula of protected sodium butyrate (PSB) during the whole growing-fattening period.ad libitum for all the pigs. Animals were raised following European animal welfare regulations for pig farms (COUNCIL DIRECTIVE 2001/88/EC of 23 October 2001).Selected pigs  were raised in a small commercial fattening unit . During the fattening period, the animals were fed with three different diets  free of antibiotics . DrinkabA feed additive  was administered to animals from 4 randomly selected pens (treatment group -TG-) along the whole period. This feed additive is a form of sodium butyrate (70%), part of which was protected with vegetable fat  in order to be able to reach the distal part of the intestinal tract, according to manufacturer. The remaining 4 pens were fed with the same diets without the additive (control group -CG-).Piglets entered into the growing-fattening unit at 10 weeks of age and remained there until slaughter, that is, when they reached an average live weight of 100 ± 10 kg (≈6 months old). The treatment began 15 days after pigs entering into the fattening unit and a dose of 3 kg of the protected sodium butyrate (PSB) per ton of feed was used for the whole period, and for each of the three different diets that were administered. At slaughter, intestinal content from the colon of 18 randomly selected pigs (9 from the TG and 9 from the CG) was collected for laboratory analysis.® 24 homogenizer for 2 × 30 s at 6500 rpm and 10 s delay between cycles. Lysis was completed at 95 °C for 5 min. Finally, DNA was eluted in 40 μL elution ATE buffer. Once DNA was extracted, DNA concentrations were measured with Qubit® 4.0 fluorometer (Invitrogen) and dsDNA HS (high sensitivity) Assay Kit (Invitrogen). DNA purity was assessed by measuring the A260/A280 with NanoDrop® ND-1000 Spectrophotometer V3.0.1  and monitored on 1% agarose gels.One gram of colon content was collected and immediately frozen at −80 °C until processed. Bacterial DNA was extracted from frozen samples using a QIAamp Fast DNA Stool Mini Kit  and following the manufacturer’s instructions. Fecal samples were mixed with 1 mL InhibitEX buffer in SK38 tubes and processed by using the Precellys® High-Fidelity PCR Master Mix (New England Biolabs). 1X loading buffer (contained SYBR green) was mixed with PCR products and amplicons were detected by electrophoresis on 2% agarose gel. Samples with a bright main band between 400–450 bp were chosen for further experiments. PCR products were mixed in equidensity ratios. Then, the mixture of PCR products was purified with Qiagen Gel Extraction Kit .Depending to the concentration, DNA was diluted to 1 ng/μL using sterile water. 16S rRNA gene of V3-V4 region was amplified using specific primers (515F-806R)  with a b® Kit for Illumina, following manufacturer’s recommendations and index codes were added. The library quality was assessed on the Qubit® 2.0 Fluorometer (Thermo Scientific) and Agilent Bioanalyzer 2100 system. Finally, the library was sequenced on an Illumina MiSeq platform at Novogene , and 250 bp paired-end reads were generated. Output data were stored in FASTQ format.Sequencing libraries were generated using NEBNex Ultra DNA Library PrePaired-end reads were assigned to samples based on their unique barcode and truncated by cutting off the barcode and primer sequence. These reads were merged using FLASH . Qualityt-test, Wilcox, and Tukey tests (p < 0.05).Alpha diversity was used to measure within-groups microbial diversity (CG and TG). Simpson, Shannon, ACE, and Chao1 indexes were calculated with QIIME (Version 1.7.0) and displayed with R software (Version 2.15.3). The differences in the alpha diversity indexes between groups were analyzed by t-test, Wilcox, and Tukey tests (p < 0.05).In order to estimate the dissimilarities between groups (beta diversity), both weighted and unweighted Unifrac were calculated by QIIME 1.7.0. Analysis of similarities (ANOSIM) and permutational multivariate analysis of variance (Adonis) were conducted using the vegan R package . Differep < 0.05) among groups. A t-test was carried out at various taxon ranks, including phylum, family, genus, and species. In addition, the microbial community differences between TG and CG diets were analyzed by the linear discriminant analysis (LDA) effect size (LEfSe) [Statistical analyses were performed to determine those taxa whose abundance varied significantly ( (LEfSe) . LEfSe mAfter quality control and chimera removal, the minimum and maximum of high-quality sequences in the samples were 101,778 and 191,444, being the average 157,755 sequences. The maximum percentage of chimeric sequences found in the samples was 17.8%, indicating a good performance of the sequencing.The total number of OTUs identified was 4697, from which 3542 OTUs (75.4%) were shared by the CG and TG groups. Each sample had, on average, 2389 OTUs (range: 1928–2875). The rarefaction curves (not presented) showed asymptotic tendency indicating that sequencing depth was adequate for characterizing the pig gut microbiota in the present study.Firmicutes -62.0%-, Bacteroidetes -25.3%-, Proteobacteria -3.7%-, and Spirochaetes -3.2%-).The gut microbiome dataset from the TG and CG was composed by more than 35 phyla, with four of them comprising almost 95% of all the bacteria . In t-test analysis.No statistically significant differences in the weighted and unweighted Unifrac analyses between the TG and the CG were found, but both the analysis of similarities (ANOSIM) and the permutational multivariate analysis of variance (Adonis) showed significant community differences between the CG and the TG  treated for a short period of time ,37,38,39p > 0.05). These alpha diversity indexes suggested a similar evenness of this OTUs distribution. Chao and ACE indexes were also similar for both groups, meaning no differences in microbiota richness between the CG and the TG. Indeed, the CG and the TG shared more than 75% of the OTUs identified. It is interesting to note that the high alpha diversity values observed for both groups in our study were similar to those found in sows [No significant differences in overall microbial diversity were detected between the CG and the TG. A high diversity was observed in both groups, as indicated by a Simpson index close to 1 and a Shannon index around 7, both being similar for the CG and TG . However, both the t-test and the LEfSe analyses detected specific taxa that differed from one group to the other. Thus, at the phylum level, we only found an increase of bacteria from the low-represented phylum Deinococcus-Thermus in the TG compared to the CG  to finishing (10%) [Prevotella in the pig gastrointestinal tract, some of which were clearly more abundant in the pigs from the TG (Prevotellaceae were promoted when sodium butyrate was supplemented [ng (10%) . More thm the TG . Previoulemented , suggestPrevotella genus have found contradictory results with regard to its relationship with pig feed efficiency and growth performance, maturation of mucosal immunity or interactions with other commensal bacteria. In general, Prevotella has been associated positively with feed efficiency and growth performance [Prevotella and Ruminococcus have been previously described as predominant and exclusive genera associated to two main enterotypes: the enterotype A in which it would predominate Prevotella and Mitsuakella; and enterotype B, with Ruminococcus and Treponema. Better growth traits have been found in those pigs with Prevotella predominant gut microbiota [Ruminococcaceae was observed in the TG, but was increased in CG, supporting this co-exclusion effect. Since zootechnical parameters could not be measured in this study, the potential positive link between Prevotella predominant gut microbiota and favorable pig performance could not be studied.Studies on the formance ,49, likeformance . Moreovecrobiota . InteresPrevotella may also contribute to the maturation of mucosa immunity through the production of acetate, which is further used by other microbial species to produce butyrate. These SCFAs would participate in the communication between the microbiota and the gut immune system and help to maintain the anti/pro-inflammatory balance [ balance . It appe balance .Lachnospiraceae, Peptostreptococcaceae, Peptococcaceae, and Terrisporobacter are a group of bacteria characterized by producing SCFA after degradation of indigestible plant-derived polysaccharides . Within this group, Lachnospiraceae may be one of the most studied, with some members of this family showing strong hydrolyzing activities, being butyrate producers and acetate consumers, especially at a mildly acidic pH. Other Lachnospiraceae species and strains, however, produce formate, lactate, or H2 in addition to butyrate [Blautia, which was also found increased in the TG in this study) and the production of butyrate with the control of gut inflammatory processes, atherosclerosis, and maturation of the immune system [butyrate . Studiese system . Memberse system , or evene system ,55,56, bPeptostreptococcaceae and Terrisporobacter. The former appeared to be more prevalent in healthy than in disease animals. They have been inversely related to dysfunction of the intestinal barrier in rats [Terrisporobacter, its abundance has been correlated with body weight, triglyceride, and worse serum lipid profile in elder women [Less studied have been  in rats , and pos in rats , thus suer women , thus beer women , but it Clostridium butyricum was significantly increased in the TG  that may also help to reduce the presence of enteric pathogens. In any case, it should be noted that the role that a given taxon may have on gut health is likely influenced by the interactions of numerous variables, such as age, diet, environment, treatments, the presence of other taxa, infections or even the physiological status of the animal. Therefore, direct comparisons between studies are difficult.The addition of PSB during the whole growing and fattening period at a dose of 3 kg per ton of feed did not significantly modify the overall richness of microbiota composition of pigs at slaughter, but significant changes in some specific taxa were detected. According to previous studies, most of the changes observed would be likely associated with better gut health parameters. An increase in the abundance of SCFA-producing strict anaerobes was detected (


Granulomatosis with polyangiitis (GPA) and rheumatoid arthritis (RA) have shared features including vasculitis, ocular inflammation, interstitial lung disease, and arthritis but existing evidence indicates they are distinct conditions. Interestingly, the co-existence of GPA and RA has been described in the literature. Herein, we report two cases of GPA developing in patients with underlying RA and examine the relationship between the two conditions.Two cases of GPA that developed in patients with preexisting RA are described in detail. Additionally, PubMed was searched for articles in English showing an association of RA and GPA using keywords “rheumatoid arthritis, and vasculitis, and Wegener’s, and ANCA, and granulomatosis polyangiitis.”In addition to our two cases of RA and GPA overlap, 14 reports were identified in PubMed library from 1970 to 2020. Most of the cases were females , and had RA as the initial diagnosis . The mean age of RA diagnosis was 45.5 years, the mean age of GPA diagnosis was 52 years and the mean interval between both diagnoses was 101 months. Cyclophosphamide and steroid therapy were used in most of the cases.There are numerous reports of GPA and RA overlap in the literature. GPA should be considered in the differential diagnosis when vasculitis develops in patients with RA. Granulomatosis with polyangiitis (GPA) is a condition characterized by small vessel vasculitis and granulomas. Areas commonly affected in GPA include the upper airway, lower airway, skin, and kidneys. Rheumatoid arthritis (RA) is chronic autoimmune inflammatory arthritis resulting in joint destruction and systemic features. GPA and RA have shared features including vasculitis, ocular inflammation, interstitial lung disease, and arthritis but existing evidence indicates they are distinct conditions. Interestingly, the co-existence of GPA and RA has been described in the literature -11. HereTwo cases of GPA that developed in patients with preexisting RA are described in detail. Additionally, PubMed was searched for articles in English showing an association of RA and GPA using keywords “rheumatoid arthritis, and vasculitis, and Wegener’s, and ANCA, and granulomatosis polyangiitis.” Clinical details including the timing of diagnoses, age, gender, clinical manifestations, serology, and therapies are reported individually and in aggregate.Case 13 and an erythrocyte sedimentation rate (ESR) 64 mm/h. A chest computed tomography (CT) scan showed a new cavitary lesion measuring 31 x 78 mm in the right lower lung lobe, a 16 x 12 mm nodular density in the left lung base with central cavitation, and several ill-defined thin-walled cavitary lesions in both lung apices measuring between 1 and 2 cm in diameter , and proximal interphalangeal joints, a positive rheumatoid factor (RF), and a positive cyclic citrullinated peptide (CCP). Her past medical history was also significant for diabetes, hypertension, and hypothyroidism. Her RA had been well controlled on leflunomide and low-dose prednisone. Initial evaluation showed a white blood cell (WBC) count of 11,300 /mmSputum cultures for Mycobacterium tuberculosis were negative. Laboratory testing revealed cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) titer of 1:160 and an elevated proteinase 3 (PR3) antibody of 4.7 units . Serial ANCA testing showed a peak titer of 1:320, with PR3 antibody of 26 units. Her first lung biopsy showed focal acute and chronic inflammation, fibrinoid necrosis, and hemorrhage. A second lung biopsy showed fragments of densely fibrous tissue with acute, chronic, and non-caseating granulomatous inflammation consistent with a diagnosis of GPA. No acid-fast bacilli, fungal organisms, or malignant cells were identified. The patient was given two infusions of rituximab 1000 mg intravenously (IV), 15 days apart with methylprednisolone 100 mg IV. Her symptoms as well as her cavitary lung lesions gradually improved. Both RA and GPA remained under good control on maintenance methotrexate (MTX) and prednisone.Case 2A 58-year-old Indian female presented with 10 days of dyspnea and hemoptysis. She had a past medical history of RA, diagnosed at age 57 after developing bilateral MCP synovitis, elevated RF of 134 IU/mL, elevated ESR of 116 mm/hour, and hand radiographs showing periarticular osteopenia and bony erosions. Her RA was controlled on MTX, hydroxychloroquine, and low-dose prednisone when she presented with a serum creatinine of 5.5 mg/dL (baseline 1.6 mg/dL) and proteinuria. A chest CT scan showed airspace disease involving the right upper, middle, and lower lobes and left upper lobe concerning diffuse alveolar hemorrhage (DAH) Figure .Anti-PR3 c-ANCA titer was elevated at 1:320. She was intubated and bronchoalveolar lavage (BAL) confirmed the presence of DAH. Biopsy of the bronchiolar wall showed chronic granulomatous inflammation and fibrosis consistent with GPA. She was given cyclophosphamide 500 mg IV, methylprednisolone IV, and plasmapheresis. She gradually improved and was eventually extubated and discharged home in stable condition. She was discharged on oral cyclophosphamide, which was later switched to azathioprine. Her RA and GPA have remained in remission on azathioprine.Fourteen reports were identified in the PubMed library from 1970 to 2020. We summarized the clinical and pathological features of those cases in Table Including our two cases, most of the cases were females , and had RA as the initial diagnosis . The mean age of RA diagnosis was 45.5 years, the mean age of GPA diagnosis was 52 years and the mean interval between both diagnoses was 101 months. ANCA and RF antibodies were positive in most of the cases. Cyclophosphamide and steroids were the most common vasculitis treatment regimen.GPA is one of three known subsets of ANCA-associated vasculitis (AAVs) as outlined in the 2012 revision of the Chapel Hill nomenclature system . RA has RA and GPA have some similar features. For example, most patients with GPA will develop arthralgia or arthritis at some point in the disease course ,18; howeThe etiology of the RA and GPA overlap is not well understood. One possible explanation is that the two conditions could share a common genetic predisposition. Both RA and ANCA-positive GPA were shown to have an increased frequency of a functional polymorphism 620W) of the protein tyrosine phosphatase non-receptor 22 gene (PTPN22) when compared to healthy controls W of the . FinallyCyclophosphamide and steroids were used in the majority of the reported cases, but we used rituximab successfully in one of our cases. Rituximab is an approved treatment for both RA and GPA so intuitively seems to be a good choice for the overlap condition. There are published case reports of the effective use of rituximab for the treatment of patients with coexisting GPA and RA . Both GPA and RA are rare autoimmune conditions that can rarely co-exist. In addition to our two cases, there are 14 reports of this overlap in the literature. The majority of the cases were females, had RA as the initial diagnosis, and had an average interval between diagnoses of 101 months. Signs of vasculitis especially in the setting of positive ANCAs in patients with RA should prompt consideration of GPA. Rituximab should be studied as a treatment for this overlap condition as it is already an approved treatment for both conditions.


Determination of trace amounts of vitamins in multi-component feed premix is a troublesome analytical procedure. In this study, a simple and rapid high-performance liquid chromatography (HPLC) method was developed and validated for the concurrent detection and quantitation of four water-soluble vitamins such as thiamine, riboflavin, pyridoxine, and cyanocobalamin in veterinary feed premixes.The chromatographic separation of the vitamins was carried out at 35°C temperature on a reversed-phase C18 column using a gradient pump mode. Mobile phase constituents were solvent (a): 25 mM Potassium dihydrogen phosphate and 5 mM sodium hexanesulfonate in deionized water having pH-4.0 and solvent and (b) 5 mM sodium hexanesulfonate in methanol. Detection was performed with HPLC ultraviolet/visible detection set at 278 and 361 nm wavelength in two different channels. The flow rate was 1.2 mL/min and the total run time was 25 min.2>0.999) at concentration of 5, 10, 15, 20, 25, and 30 μg/mL for all vitamins. The limits of detection values were 0.0125, 0.0017, 0.0064, and 0.0065 μg/mL for thiamine, riboflavin, pyridoxine, and cyanocobalamin, respectively, and the limits of quantification values were 0.0378, 0.0051, 0.0213, and 0.0198 μg/mL for thiamine, riboflavin, pyridoxine, and cyanocobalamin, respectively. The recovery percentages ranged from 88% to 115%.The method was validated according to the International Conference on Harmonization and Food and Drug Administration guidelines and acceptance criteria for system suitability, precision, linearity, and recovery were met in all cases. The relative standard deviation for system suitability and precision was <2% for all vitamins. The linearity of the calibration curves was excellent (RThe overall parameters of the proposed method met the validation criteria and this method could be a highly desirable technique for routine analysis of water-soluble vitamins in veterinary feed premix. Vitamins are critical and biologically active organic compounds that are minor but essential constituents of food required for normal metabolism in human and animal bodies ,2. Feed Water-soluble vitamins have been extensively used as vitamin-mineral feed premix in animal production, especially in the poultry industry. The necessity of balanced vitamin-mineral premix in the poultry sector is increasing day by day to optimize the diet compositions and meet the demand of modern poultry production . While vHowever, precise and routine analysis of water-soluble vitamins in veterinary feed premix is challenging due to the complex composition and unstable nature of the target analytes. Many factors can affect the stability of these vitamins such as heat, light, pH, air as well as interactions with other feed components ,14. FurtThe liquid chromatography technique has been widely applied for vitamin analysis from different matrices with some drawbacks such as low reproducibility, longer retention time, and complex mobile phases associated with longer column equilibration, and the total run time of the analysis upper to 60 min ,19. Due 1), riboflavin (B2), pyridoxine (B6), and cyanocobalamin (B12) in veterinary feed-premix.Hence, the current study aimed to develop a simple, rapid, and validated HPLC technique for the determination of water-soluble vitamins such as thiamine , Dhaka, Bangladesh.2PO4), sodium hexanesulfonate, and methanol (HPLC grade) used in this study were purchased from Sigma-Aldrich and certified reference standard (CRS) of thiamine , riboflavin , pyridoxine hydrochloride , and cyanocobalamin  were purchased from Europian Pharmacopoeia Reference Standard, Council of Europe, EDQM CS 30026F-67081, Strasbourg, Cedex. Double deionized (DI) water used in this study was obtained from a water deionization plant . All solutions were sonicated and filtered through a 0.45 mm filter using a vacuum filtration unit  before use.Potassium dihydrogen phosphate  for thiamine, riboflavin, pyridoxine, and 361 nm (Channel-B) for cyanocobalamin. The whole chromatography was performed at ambient temperature.The high-performance liquid chromatographic system  with a data processing unit Empower-3 software was used in this study. HPLC column Waters X-Bridge (4.6×150 mm), 5 mM Packing C18 was used for the separation of vitamins. A gradient pump mode was used where 25 mM KHWeighed accurately 10 mg from each of thiamine, riboflavin, pyridoxine, and cyanocobalamin CRS and transferred into four 100 mL amber color volumetric flasks separately. Initially, 30 mL of DI water were added to each flask and the contents were shaken vigorously by a vortex mixer for 3 min and sonicated for 10 min in an ultrasonic bath. Then, the solutions were diluted to volume with DI water and mixed thoroughly by vortex mixer. These solutions were used as reference stock standard solutions and kept in a refrigerator for further use. Working standard solutions were prepared from stock standard solutions. Before injecting into the liquid chromatography system, the solutions were filtered through a 0.45 mm polyvinylidene difluoride (PVDF) syringe filter.The procedure of standard solution and sample preparation was almost the same. Briefly, 5.0 g of veterinary feed-premix enriched with thiamine, riboflavin, pyridoxine, and cyanocobalamin was accurately weighed and transferred into a 100 mL amber color volumetric flask. Initially, 30 mL of DI water were added to the flask and the contents were shaken vigorously by a vortex mixer for 3 min and sonicated for 10 min in an ultrasonic bath. Then, the content was diluted to volume with DI water and mixed thoroughly by a vortex mixer for 3 min. Thereafter, the mixer was filtered with Whatman 1 Filter paper. Finally, the sample solution was transferred into the sample vial after filtering with a 0.45 mm PVDF syringe filter for liquid chromatography.Method validation of the present study was performed by measuring the basic parameters of the validation process such as system suitability, precision, linearity, limits of detection (LOD), limits of quantification (LOQ), and recovery. The validation parameters were evaluated using recommended guidelines of the International Conference on Harmonization (ICH)  and the The system suitability was evaluated by six replicate analyses of a standard aqueous mixture of all vitamins. The acceptance limit of the different parameters for system suitability of the method is calculated according to the guidelines of ICH and FDA where the acceptance criteria are the percentage of relative standard deviation (RSD) for retention time and peak area (PA) is < 2%, the number of theoretical plates (TP) more than 2000, tailing factor (TF), and peak resolution (RS) >2.The precision of the method was evaluated based on repeatability and intermediate precision. The repeatability was calculated on the results obtained from the same day for six independent mixer solutions of the same concentration (10 μg/mL) and the intermediate precision was evaluated by calculating the repeatability of the same concentration (10 μg/mL) by two analysts on different days. The percentage of RSD was calculated for estimating the precision of this study.To evaluate the linearity, six standard mixtures of thiamine, riboflavin, pyridoxine, and cyanocobalamin were prepared and a linear equation was established for each vitamin by plotting the PAs versus the concentrations. Three calibration curves were obtained on three consecutive days with a specified standard concentration of each vitamin. Linearity was calculated by running six standard mixtures of each vitamin, at final concentrations of 5, 10, 15, 20, 25, and 30 μg/mL.The lowest qualitative and quantitative concentrations for the tested linearity range were calculated for each vitamin according to the guidelines of ICH-2000. Both LOD and LOQ were calculated using the expression: k x S.D/b, where k=3.3 for the LOD and 10 for the LOQ, S.D=The standard deviation of the intercept, and b=Slope of the calibration curve tested for linearity.The recovery studies were carried out by spiking different amounts  of each vitamin in the pre-analyzed formulation blank matrix sample along with the linearity range. For the estimation of recovery, an accurate amount of each vitamin at three concentration levels  was added to approximately 1.0 g of blank matrix powder, and then the powder was extracted and analyzed for recovery using the formula: recovery (%)=(amount obtained/amount spiked)×100.Data collected in this study were analyzed using Statistical Package for the Social Sciences version 16 statistical package by one-way analysis of variance and by independent samples Student’s t-test. Linear regression analysis was performed using the least square method.This study demonstrates the development and validation of a precise analytical method where the validation criteria -23 met i2>0.999) within the concentration range of 5-30 μg/mL. The lowest qualitative and quantitative concentrations for the tested linearity range were calculated for each vitamin. The LOD for thiamine, riboflavin, pyridoxine, and cyanocobalamin is found to be 0.0125, 0.0017, 0.0064, and 0.0065 μg/mL, respectively, and the LOQ for thiamine, riboflavin, pyridoxine, and cyanocobalamin is found to be 0.0378, 0.0051, 0.0213, and 0.0198 μg/ mL, respectively, (The system suitability parameters  reveal tctively, . From thIn this study, a simple and precise analytical method is developed with an HPLC column for rapid and reliable analysis of water-soluble vitamins in complex veterinary feed premix. The simple technique for sample preparation and mobile phase containing water and methanol make the method more economical and desirable for the quantification of water-soluble vitamins in feed premixes. The recovery of each vitamin with the proposed procedure in the feed premix formulation is also high enough with their respective label claims. Therefore, this method could be a validated analytical procedure for accurate determination of water-soluble vitamins in multi-component veterinary feed premix and might be a precise technique to check the standard and quality of the feed premix intended to be used for increased livestock production.MZH: Conceptualized and designed the study. MZH and SMSI: Generated the data. MZH and SMSI: Analyzed the data. MZH: Drafted the manuscript. MMK: Edited and finalized the manuscript. All authors read and approved the final manuscript.


Salmonella spp., the presence of cadaverine and putrescine diminished by 62 and 78%, respectively, due to the addition of cava lees. The addition of cava lees phenolic extract also showed an anti-aminogenic effect (21% for cadaverine and 40% for putrescine), although in a lesser extent than cava lees. Cava lees and their phenolic extract were shown to be an effective strategy to control the undesirable accumulation of high levels of biogenic amines during the production of fermented products.Food safety can be compromised by some bioactive compounds such as biogenic amines that can be specially found in fermented foods due to the bacterial decarboxylation of some amino acids by fermentative or spoilage bacteria. Cava lees are a winery by-product rich in fiber and phenolic compounds and previous works have raised their revalorization from a food safety point of view. The aim of the current work was to investigate whether the use of cava lees can help to control biogenic amine formation in bread and fermented sausages. In bread, only very low levels of biogenic amines  were found, whose content did not vary with the addition of different amounts of lees. However, the addition of lees in fermented sausages significantly reduced the formation of tyramine and cadaverine. In sausages spontaneously fermented and inoculated with  Food safety can be compromised not only by food-borne pathogens but also by some bioactive compounds of bacterial origin such as biogenic amines. These microbial metabolites  are formed by a decarboxylation of their precursor amino acids and can be found in almost all types of food in a wide range of concentrations, which may vary even within the same type of product. Histamine and tyramine can have adverse health effects, such as histamine intoxication, histamine intolerance or hypertensive crises caused by the interaction between tyramine and monoamine oxidase inhibitor (MAOI) drugs . In factBesides the food safety issue, because the accumulation of biogenic amines in foods can be associated with the activity of spoilage bacteria, a high content of these compounds is considered a chemical marker of insufficient food freshness or poor hygiene in the manufacturing and/or food preservation processes . AdditioSaccharomyces cerevisiae , lyophilized , ground and stored in tubes protected from light and humidity until use. A lees phenolic extract (LPE) with a total phenolic content of 152.2 ± 3.5 mg GAE/g was obtained from the cava lees using the method described by Cava lees were provided by the winery Freixenet S.A. . To remove any remaining cava, the wet lees were centrifuged at 18,000 × Saccharomyces cerevesiae) and 10 g of salt. Four batches of bread were made: without cava lees (control) and with three different amounts of cava lees . These percentages were selected for showing a growth promoting effect on fermentative lactic acid bacteria (LAB) of the sourdough with total counts determined using MRS medium at 30°C under aerobic conditions during 72 h. The sourdough was prepared following the procedure described by Bread was prepared using 500 g of wheat flour, 150 g of sourdough, 285 g of water, 4 g of lyophilized yeast (The meat batter was prepared by mixing minced pork lean and ground fat (8:2) through a 6 mm plate. The ground meat was then mixed with (g/kg): sodium chloride (25), dextrose (7), black pepper (3), sodium ascorbate (0.5), sodium nitrite (0.15), and potassium nitrate (0.15).in vitro bacterial growth in MRS medium of different strains of starter cultures, such as Latilactobacillus sakei, Lactiplantibacillus plantarum, Latilactobacillus curvatus, Lacticaseibacillus casei, and Limosilactobacillus fermentum  and with 5% (w/w) cava lees. According with previous studies, 5% of cava lees was the most effective amount to enhance the ermentum , as wellermentum . For eacSalmonella enterica were inoculated to the meat batter at a final level of ca. 6 log10 CFU/g (same amount for each strain): CTC1003 (serotype London), CTC1756 (serotype Derby) and CCUG34136  (L. sakei (formerly Lactobacillus sakei) CTC494, producer of the bacteriocin sakacin K  . Portionakacin K , and L. The analyzed samples corresponded to the meat batter (time 0), 8–9 days of ripening (depending on the experiment) and the finished product after 21 days of ripening. Each batch was prepared in triplicate.g, 4°C, 25 min) and the supernatant was collected in a 25 mL volumetric flask. This extraction process was repeated twice more, and the final volume of the extract was adjusted with 0.6 M perchloric acid. The samples were filtered through a 0.22 μm GHP filter. All determinations were done in triplicate.Twelve biogenic amines  were determined in bread (sourdough and baked bread) and fermented sausages (at different time points during fermentation and ripening by triplicate). The biogenic amine content in the cava lees was also analyzed. Ultra-high efficiency liquid chromatography coupled to fluorometric detection (UHPLC-FL) was used according to ortho-phthaldehyde and a fluorometric detection (Ex: 340 nm and Em: 445 nm).Chromatographic separation of the biogenic amines was performed using an Acquity UPLC BEH C18 1.7 μm (2.1 mm × 50 mm) reversed phase column , followed by an on-line post-column derivatization with The aqueous content was determined  and the L. sakei BAP110 and Salmonella spp.) was evaluated using the method described by L. sakei CTC494 was previously established by The amino acid decarboxylase activity of the strains (post hoc test were performed (SPSS software). Differences with p < 0.05 were considered statistically significant.To determine the statistical differences in biogenic amine contents between the different batches of fermented products, a one-way ANOVA and the Tukey HSD S. cerevisiae) and LAB, mainly Lactobacillus spp. and Leuconostoc spp., whose acidifying and proteolytic properties influence the aromatic quality and rheology of bread. Despite this considerable microbial activity, the sourdough was found to contain only low levels of putrescine and spermidine, both naturally present in flour and therefore coming from this ingredient  reduced cadaverine accumulation by more than 76% compared to the control batch.In the control batch, cadaverine was the dominant amine, representing 41% of the total amine content, followed by spermine (23%) and tyramine (18%), whereas putrescine and spermidine were present at the lowest amounts. The effect of cava lees in fermented sausages was only evaluated with the addition of 5% of lees, since this was the amount that showed an antimicrobial effect in this kind of product . In the Based on these promising results, the potential reductor effect of cava lees on biogenic amine formation during the production of fermented sausages was studied in more depth using different batches of fermented sausages from a previous study .Salmonella, a bacterial genus generally linked with a high capacity to form biogenic amines. However, as aminogenic capacity varies among strains, it is necessary to carry out a case-by-case evaluation , and moderate levels of histamine (200 mg/L); the strains were not able to form tyramine. The production of putrescine, cadaverine, and histamine is frequently associated with the activity of Gram-negative spoilage bacteria (Pseudomonas and Enterobacteria) and food-borne pathogenic bacteria  to avoid the concentration effect of the drying process. In the meat batter used in the manufacturing of fermented sausages for both experiments, spermine and spermidine were the only two amines detected, with contents of 89.2 ± 0.2 and 3.4 ± 0.1 mg/kg dm, respectively, which did not change significantly during the fermentation and ripening process in any of the batches. These results confirm the physiological origin of these polyamines from meat. Although the cava lees contained spermidine, the proportion in which the lees were added to the sausages (5%) was too low to create significant differences with the control batches.During the fermented sausage processing, three amines were detected, cadaverine, putrescine and tyramine, the concentrations varying considerably between experiments and/or batches . PhysicoSalmonella strains to synthesize these diamines. Both amines are commonly found in fermented meat products, although usually at relatively low levels  , cadaverine was the major amine, reaching levels of 1,484 mg/kg dm . Signifiby EFSA) . Howeverby EFSA) . The conby EFSA) . For thiby EFSA) . In the p < 0.05). The markedly lower counts of Salmonella (up to 2.7 log10) found in fermented sausages formulated with cava lees (The addition of cava lees (L1) only affected the formation of cadaverine and putrescine, with values in the finished product being 62 and 78% lower than in the control batch C1, respectively , with reductions of up to 91% for putrescine, 88% for tyramine, and 74% for cadaverine. The high efficacy with which the starter culture inhibited amine formation meant it was impossible to observe any synergistic effect with cava lees.Finally, the formation of cadaverine, putrescine, and tyramine was inhibited in the batches added with the starter culture i CTC494 , a highli CTC494 . Numerou strains . Among tmulation . Bover-CpH, formulation, sausage diameter, etc.) and technological (temperature and humidity)  , with levels of 525 and 212 mg/kg dm in the final product, respectively . The forumidity) . Therefo8 in C2) . The effogenesis . TyraminSalmonella than C2 at the end of the ripening (differences of 0.71 log10). Therefore, the reduction in amine levels of E2 could be due to the polyphenols from LPE, as indicated by some other studies performed on different types of meat products. For example, the addition of phenolic extracts from tea, grape, bamboo, or roses induced a significant decrease in levels of cadaverine, tyramine, histamine, and/or putrescine, which was always correlated with lower counts of spoilage bacteria in the polyphenol-enriched products (The LPE added in this experiment (E2) also had a significant aminogenesis reducing effect, 21% lower content for cadaverine and 40% for putrescine compared with the control (C2) . As repoproducts .L. sakei CTC494 as starter culture, both with or without LPE, avoided the formation of the three amines. In contrast, the use of L. sakei BAP110 culture, also without aminogenic capacity in vitro, prevented the formation of putrescine and cadaverine but not totally that of tyramine (As in the case of experiment 1, the use of tyramine . MoreoveIt should be noted that the formation of histamine was not observed in any batch of fermented sausages. According to various studies, histamine is found in less frequency in meat products or only in low quantities. However, the occasional presence of extremely high levels of histamine has been linked to hygienically defective raw materials .The two fermented products considered in this study showed important differences regarding the occurrence of biogenic amines. In the case of bread, only very low putrescine, cadaverine and/or spermidine contents were found, mainly proceeding from raw materials, and without significant differences depending on whether or not cava lees were added. On the contrary, the addition of cava lees or its phenolic extract in the formulation of fermented meat products has been shown to be an effective strategy to reduce the high levels of biogenic amines, such as putrescine and cadaverine, although this effect was not as effective as the use of starter cultures. In view of the obtained results on the anti-aminogenic effect in meat fermented products, it would be convenient to carry out further studies assessing a wider range of concentrations of cava lees or its phenolic extract and also to extend it to other fermented products.The original contribution presented in this study are included in the article, further inquiries can be directed to the corresponding authors.ML-M, MV-C, AJ, and SB-C: conceptualization. SH-M, NF-B, AM-G, OC-B, and ML-M: investigation. SH-M, OC-B, and ML-M: writing—original draft preparation. SH-M, NF-B, OC-B, MR-A, EL-T, ML-M, AJ, SB-C, and MV-C: writing—review and editing. MV-C, AJ, and SB-C: supervision. All authors have read and agreed to the published version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Gastrointestinal stromal tumors (GISTs) albeit rare, are the most common mesenchymal neoplasms of our gastrointestinal (GI) tract. GISTs present with nonspecific symptoms and are found incidentally on endoscopy or imaging. A significant portion of GIST diagnoses expresses KIT/CD117 and DOG-1 tissue markers which are pathognomonic for GIST. More recently, Ki-67 was found to be a significant prognostic marker for determining the risk of recurrence. We present a patient with a mesenchymal mass in the small intestine with pathognomonic features of GIST and expression of Ki-67, an important immunocytochemical marker of proliferation.The patient was a 71-year-old male with a history of hyperlipidemia and hypertension. He presented to the emergency department complaining of bloody diarrhea for two days, with associated nausea, vomiting, and abdominal cramping. Initial blood pressure on presentation was 77/52 mm Hg. Computed tomography (CT) of the abdomen and pelvis revealed a large solid mass with cystic components. The mass was not visualized with esophagogastroduodenoscopy or colonoscopy, and surgical intervention was warranted. A 14 cm x 11.5 cm x 10 cm tumor was found in the ileum. The tumor was excised with small bowel segmental resection and the specimen was sent for pathological evaluation. Immunohistochemical analysis confirmed the diagnosis of GIST with diffuse CD117/c-Kit protein expression. The tumor was high grade with a high mitotic rate at 30 mitoses/50 high-power fields (HPF) and had spindle cell morphology. Of note, 10% of the tumor cells were positive for Ki-67.GISTs have a high risk of recurrence and a more favorable prognosis with advancements in management. Prior to imatinib therapy in the early 2000s, GISTs prognosis was very poor, as they are resistant to most conventional chemotherapeutic agents and radiation. While the prognosis is fair, surgical resection and imatinib therapy have improved outcomes and risk of recurrence. Prognosis and risk of recurrence can be determined by assessing the mitotic rate, tumor size, and recently, expression of Ki-67. Ki-67 provides a reliable and reproducible approach to assess the prognosis of GIST. Gastrointestinal stromal tumors (GISTs), first discovered in the 1980s, did not become significant till the 21st century . They arThe patient was a 71-year-old male with a history of hyperlipidemia and hypertension. He presented to the emergency department (ED) complaining of bloody diarrhea for two days, with associated nausea, vomiting, and abdominal cramping. His presenting blood pressure was 77/52 mmHg.CT of the abdomen and pelvis was significant for a large solid mass (13.4 cm x 11.2 cm), with cystic components in the lower abdomen, located slightly eccentric on the right  and had spindle cell morphology. The tumor was infarcted with a 3.5 cm x 2 cm disruption of the mass consistent with hemorrhage and ischemia. Of note, 10% of tumor cells were positive for Ki-67. The tumor cells were negative for Desmin, S100, Mart-1, AE1:3, p53 wild-type tumor markers. The patient was discharged home and instructed to follow up on an outpatient basis. No further studies or procedures were deemed necessary at that time.Our patient presented with an abdominal mass with features that were pathognomonic for GIST, in the setting of an acute GI bleed with nausea, vomiting, and abdominal cramping. GISTs are known to arise from the mesenchymal tissue of the GI tract and most studies specifically report that they arise from the interstitial cells of Cajal, also known as the pacemakers cells of the GI tract ,2,4,5. ADiagnosing a GIST requires a tissue sample for immunohistochemical and morphological analysis . The safThe treatment of GISTs is dictated by size, location, and spread . Under mSurgical treatment is only effective in 60% of cases of localized disease . GIST prThe GIST in our patient was significant for 10% Ki-67 expression. Ki-67 is an important immunocytochemical marker of proliferation for several different tumors [In terms of follow up, there are not sufficient data suggesting an appropriate time frame for follow up status post diagnosis and resection of GIST ,3,4. SomWith the increasing prevalence of GISTs, it is imperative to understand the necessary steps needed to diagnose and manage GISTs reliably and efficiently. Successfully treating GISTs requires a multi-disciplinary approach, and albeit a rare diagnosis, the risk of recurrence, malignant potential, and poor prognosis makes understanding and treating GIST an important tool for clinicians to have. Given the limited but significant Ki-67 data, future studies should focus on Ki-67’s importance in determining prognosis as Ki-67 provides a reliable and reproducible approach to assess prognosis. Future studies should also focus on compiling guidelines or criteria to allow clinicians to use Ki-67 more accurately and consistently as a prognostic indicator.


What are the publication patterns for neurology publications in general medicine journals, and how do they compare with other specialties?New England Journal of Medicine (NEJM) published more neurology articles than other journals. In the top 5 general medicine journals, there were more publications in neurology than in immunology, endocrinology, gastroenterology, or pulmonology.In this cross-sectional bibliometric analysis of the top 5 most cited general medicine journals, the NEJM, and general medicine journals published more articles in neurology than in other medical specialties.In this study, neurology articles were published most often in  This cross-sectional study examines the publication patterns of neurology articles in general medicine journals during a 10-year period using a bibliometric approach. A significant portion of neurology literature is published in general medicine journals. Despite this, a detailed examination of publication patterns of neurology articles in these journals has not yet been carried out.To examine the publication patterns of neurology articles in general medicine journals during a 10-year period using a bibliometric approach.nervous system diseases, immune system diseases, endocrine system diseases, gastrointestinal diseases, and respiratory tract diseases. Data analysis was conducted from February 2019 to December 2020.This cross-sectional bibliometric analysis identified the top 5 general medicine journals using the 2017 Journal Citations Report. Four other medical subspecialties  were selected for comparison of publication patterns with neurology. Using MEDLINE, the 5 journals were searched for articles published between 2009 and 2018 that were indexed with the following MeSH terms: Publications were characterized by journal, specialty, and study design. These variables were used for comparison of publication numbers.New England Journal of Medicine , Lancet (JIF 53.3), JAMA (JIF 47.7), BMJ (JIF 23.6), and PLOS Medicine (JIF 11.7). Our bibliometric search yielded 3719 publications, of which 1098 (29.5%) were in neurology. Of these 1098 neurology publications, 317 (28.9%) were published in NEJM, 205 (18.7%) in Lancet, 284 (25.9%) in JAMA, 214 (19.5%) in BMJ, and 78 (7.1%) in PLOS Medicine. Randomized clinical trials were the most frequent neurology study type in general medicine journals (519 [47.3%]). The number of publications in each of the other specialties were as follows: immunology, 817; endocrinology, 633; gastroenterology, 353; and pulmonology, 818.The general medicine journals with the 5 highest journal impact factors (JIF) were The results of this study provide some guidance to authors regarding where they may wish to consider submitting their neurology research. Compared with other specialties, neurology-based articles are published more frequently in general medicine journals. Neurology-focused research articles (NFRAs) are published in a number of journal types, including general neurology journals, neurology subspecialty journals, and general medicine journals (GMJs). However, there has been little examination of the precise publication patterns of NFRAs, specifically how frequently GMJs publish neurology articles and how the publication of neurology articles compares with other specialties. Bibliometric analysis can provide data regarding productivity rates, publication patterns, and publication characteristics by providing statistical descriptions of publications based on, in part, the premise that the published literature of a field embodies the field’s knowledge.3 It uses computerized analytic techniques with the individual publication as the unit of analysis, drawing data from sources such as MEDLINE, Google Scholar, or Journal Citation Reports .4 Bibliometric methods have been used to explore the productivity of researchers, institutions, and countries within given subject areas; to examine research trends and emphases in various disciplines; and to guide policy decision making.8 The JAMA Network has served as a medium for publishing bibliometric research in various medical specialties, including dermatology, ophthalmology, critical care, and obstetrics and gynecology (OBGYN),12 but bibliometric research related to neurology has not been extensively published. Therefore, our goal was to examine publication patterns of NFRAs in GMJs using a bibliometric approach and to compare these publication patterns with other medical subspecialties.There has been considerable growth in scientific publications over time,STROBE) reporting guideline.15The institutional review board of the Children’s Hospital of Eastern Ontario deemed that ethical approval was not necessary, as this was a pure bibliometric study. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology . The JCR data was filtered by the following: (1) selected categories, Medicine, General, and Internal; (2) selected JCR year, 2017; (3) selected editions, Science Citation Index Expanded (SCIE); and (4) selected category scheme, Web of Science. We then identified the 5 journals with the highest JIFs that met the following criteria: (1) GMJ, (2) accepting adult and pediatric articles, and (3) publishing primary research reports . We then obtained each journal’s 2017 JIF,We sought to compare the publication patterns seen in neurology with 4 other medical subspecialties. To establish these 4 additional disciplines, we examined the JCR categories and selected the 4 specialties with the highest number of total citations in the JCR 2017 report that also met the following criteria: (1) the specialty must be relevant to all age groups, excluding, eg, gerontology and pediatrics, and (2) the specialty must be clinically focused. When an article was indexed with MeSH terms for more than 1 specialty, we included the article in each of those specialties.nervous system diseases, immune system diseases, endocrine system diseases, gastrointestinal diseases, and respiratory tract diseases. We further restricted the search to records with abstracts and excluded commentaries, editorials, historical articles, and letters. Records were downloaded into Reference Manager version 11 (Thomas Reuters).On April 24, 2019, using Ovid MEDLINE, we searched the 5 journals for articles published between 2009 and 2018 that were indexed with the following MeSH terms: Our search included MEDLINE classification for the following study designs: randomized clinical trials (RCTs), clinical trials, systematic reviews, case reports, cohort studies, cross-sectional studies, case-control studies, and comparative studies. A hierarchical filtering process was used to ensure all study types were mutually exclusive and that each article was only indexed for 1 study type. We reviewed a random 5% sample of the records to ensure classification accuracy for specialty and study type.P > .10), that interaction was removed, and the reduced model was fitted. Based on the final model, estimated marginal means by year, journal, and specialty were computed. Within journals, contrasts between the 4 other specialties  and neurology were estimated, averaging over years, and are displayed as ratios with 95% CIs, adjusted for multiple testing using the multivariate t-distribution method.14 All tests were 2-tailed, and analyses were conducted in R version 4.0.4 .Data analysis was conducted from February 2019 to December 2020. Models for the number of publications by year, journal, and specialty were constructed. Poisson models were initially considered; however, due to the presence of overdispersion, these models were replaced by quasi-Poisson models. The starting point was a model including main effects for year, journal, and specialty as well as all 2-way interactions. When the evidence for an interaction was weak , Lancet , JAMA , BMJ , and PLOS Medicine   had a range of 3.1 to 27.1, with a mean of 8.7  and a median (interquartile range) of 4.0 (3.7-5.5). The 4 selected specialties used for comparison with neurology were immunology, endocrinology, gastroenterology, and pulmonology.The JCR 2017 report revealed that the 5 GMJs with the highest JIFs were IF 11.7) . The oveA total of 186 of the 3719 (5.0%) results were reviewed. Accuracy was 96.2%  by specialty and 96.8%  by study design.NEJM, 205 (18.7%) in Lancet, 284 (25.9%) in JAMA, 214 (19.5%) in BMJ, and 78 (7.1%) in PLOS Medicine . RCTs were the most frequent neurology study type in general medicine journals, accounting for 519 of 1098 publications (47.3%). NEJM published 0 meta-analyses, while BMJ published 37; BMJ published 0 case studies, while NEJM published 35. Our bibliometric search yielded 3719 publications, of which 1098 (29.5%) were in neurology. Of these 1098 neurology publications, 317 (28.9%) were published in 236 = 63.2; P = .003) and between journal and subspecialty . However, there was little evidence of an interaction between year and subspecialty , and this interaction was removed from the model. Using this reduced model, the ratio of number of publications per year for each subspecialty compared with neurology was estimated within each journal , the range, mean, and median JIF were 3.1 to 27.1, 8.7, and 4.0, respectively. This trend is not limited to the specialty of neurology. For example, a bibliometric study examining the publication patterns of OBGYN articles found that the top-cited articles published in nonspecialty journals were more frequently cited than those in OBGYN journals.12 One reason that is likely driving higher JIFs in GMJs vs neurology-focused journals, and is a reason for authors to preferentially publish in these journals, is that the neurology articles published in GMJs tend to be applicable to clinicians and researchers other than neurologists.It is apparent that the top GMJs have higher JIFs than neurology-focused journals. In our study, the range, mean, and median JIFs for the top 5 GMJs were 11.7 to 79.3, 43.1, and 47.7, respectively. In 5 of the top neurology journals by JIF  reporting guideline.18It was noteworthy that NEJM, JAMA, and Lancet all have higher JIFs than specialty journals, including neurology-specific journals. However, with decreasing impact factors, authors essentially have more choice. While they could submit to PLOS Medicine, with a JIF of 11.7, they could also choose to submit to a neurology-specific journal with a similar or even higher impact factor .19There was a decrease in the number of publications of neurology  with decreasing JIF. This likely is likely because GMJs journals such as There are many factors for neurology researchers to consider when deciding where to publish their work. Researchers typically want their research to reach both a large and interested audience, which can be accomplished by publishing in a journal with a high JIF and whose scope is relevant to the topic of the publication, respectively. Whether the JIF or the scope of the journal is more important is likely highly variable among individual researchers and the nature of the publication. Further qualitative research may help to elucidate the most important factors used by authors to determine where to publish their neurology-based research.Our study has limitations. One limitation of our study, inherent to any bibliometric approach, was that we did not examine individual article records, except those in the random sample we examined to verify the accuracy of indexing. Rather, we relied on indexing in MEDLINE for classifications. Nonetheless, accuracy of the 5% sample we manually verified was very high, and thus, we can be confident that the results achieved through bibliometric methods are a true reflection of the GMJ literature. It also would have been interesting to see which neurological subspecialties were most heavily represented in high-impact GMJs, although this analysis is beyond the scope of the present study.Using the JIF to select the 5 most cited GMJs has both advantages and limitations. JIF is widely used because it is an established metric that allows for comparison of journal impact within disciplines and is designed to reduce bias toward larger journals that publish more articles annually. The main limitation of the JIF is that it does not reflect the number of citations (or impact) of individual articles but rather the number of citations of the journal. In this sense, highly cited articles published in journals with low JIF are deemed to have a lower impact in the literature than articles with fewer citations published in journals with higher JIF. Similarly, individual articles can make a disproportionate contribution to the overall JIF; as such, the JIF may not provide the most accurate assessment of the quality of the individual articles that are published within a journal. Additionally, JIF does not consider journals citing their own publications  and the context of the citation .NEJM, and more neurology articles were published in GMJs than other medical specialties. These results may provide some guidance to authors regarding where they may wish to consider submitting their neurology research, depending on the type of study design used.In this study, neurology articles were published most often in


Background and objectives: Our aim is to determine the diagnostic performance and utility of Diffusion Weighted MR Imaging (DWI) against the routine Magnetic Resonance Imaging (MRI) for the evaluation of patients with tendon injuries of the ankle and foot. Materials and Method: After institutional review board approval and informed consent taken from all the patients, ankle and foot MR imaging and DWI-Apparent Diffusion Coefficient (ADC) mapping were performed on the 81 injured tendons of 50 patients. All tendon injuries were named as Rupture (R), Partial tear (PT), and Tenosynovitis (T). Diagnostic interpretation was based on the MRI-DWI and ADC mapping, verified by either open surgery, diagnostic arthroscopy, or conservative procedures-splint application. Statistical analysis of this research was assessed by Fischer’s exact test, variance analysis test between dependent groups, Receiver Operating Characteristics (ROC) curve, and Pearson chi square statistics. Results: MRI depicted all tendon injuries with 70% sensitivity and 100% specificity, and showed a significant statistical relationship to surgical and arthroscopic references with high agreement . DWI had 100% sensitivity and 83–90% specificity for the visualization of tendon injuries with certain agreement and a significant statistical relationship to the gold standard . For all those injured tendons, DWI had 100% sensitivity for the diagnosis of R, and 92–97% sensitivity corresponding to PT and T over routine ankle MR imaging. The specificity of DWI to MRI ranged from 75 to 44% for all the injured tendons. DWI had significant statistical superiority over MRI for the visualization of R, PT, and T of all tendons included in this research (p < 0.05). Conclusions: DWI is a good imaging modality for the visualization of ankles with tendon injuries, possibly further improving the sensitivity of the classical ankle and foot MRI, and supplying more beneficial and diagnostic information than routine MR imaging on the basis of R, PT, and T of tendons at the ankle and foot. Clinical examination and conventional radiography are the first steps in evaluating whether a tendon or a ligament has been injured in the foot and ankle, but even those are not enough nor helpful in highlighting these injuries, especially when those injuries are not associated with bone avulsions and large intra-articular effusions ,2. For aLateral ankle ligament complex injuries , calcaneofibular ligament (CFL), and posterior talofibular ligament (PTFL)) are present in up to 85% of ankle sprains, making them the most frequently injured ligaments secondary to strong ankle inversion movement during lateral ankle sprains . The medMRI can be successfully utilized for the diagnosis of ankle instability, impingement, and injuries of tendons and ligaments; useful for the assessment of a wide range of soft-tissue and osseous disorders of the ankle, thereby helping the surgeon to plan an appropriate treatment; however, ankle instability and ankle impingements are diagnosed mostly based on symptoms and physical examination ,9,10,11,Rehabilitative Ultrasound Imaging (RUSI) has been used to measure the Cross-Sectional Area (CSA), thickness, and connective tissue of various muscles associated with musculoskeletal conditions that affect physical therapy and conservative evaluation . CSA andWith the advancing technology, new MRI sequences have been proposed to improve the quality of routine MRI protocol and have been applied to increase the sensitivity and specificity for the diagnosis of ankle injuries, and at the same time, to overcome the misdiagnosis of tendon injuries, especially due to the failure of MRI ,12,13.Such a new sequence: Diffusion Weighted Imaging (DWI) and Apparent Diffusion Coefficient (ADC) mapping will be analyzed in this study, our hypotheses is that DWI aids in the diagnosis of tendon injuries of the foot and ankle; its use beneath the routine ankle MRI can easily improve and strengthen the diagnostic performance of MRI. In our view, the scientific contribution of this paper to the literature is that DWI can supply adequate information in the diagnosis of ankle sprains and can collaborate with the routine MRI, which can support the early diagnosis by orthopedicians, resulting in a reliable therapeutic approach for the benefit of ankle trauma patients. Our aim is to define the utility and capacity of DWI-ADC mapping for the diagnosis of tendon injuries in the ankle and foot, with regard to routine ankle MR imaging.Between November 2012 and August 2020, 50 patients  with ankle and foot sprains were prospectively evaluated.A total of 23 left, and 27 right, ankles were included in this research. All patients underwent a detailed history and physical examination by an experienced orthopedic surgeon and his four colleagues, then referred to us for an MRI of the ankle. All patients had precise pain and ankle instability mostly due to a trauma at walking and sports and/or due to jogging injuries and accidents. Besides tendon injuries, there were also bone bruises, fractures and microfractures of bones, ligament tears, synovitis, synovial thickening, and bursitis in some patients, but none of these patients were excluded. None of the patients had a history of rheumatoid arthritis or any other sero-negative arthritis. Written informed consent was obtained from all patients prior to imaging, and the institutional review board approved the research Achilles tendon (A), tibialis posterior tendon (TP), peroneal tendons (PT), tibialis anterior tendon (TA), extensor digitorum longus tendon (EDL), extensor hallucis longus tendon (EHL), flexor hallucis longus tendon (FHL), and flexor digitorum longus tendon (FDL) injuries were all analyzed in this research. Peroneus longus and brevis were taken as one peroneal tendon, injury of either tendons or both, were taken as PT injury with regard to the comments and referral of the orthopedicians. A total of 81 tendon injuries of ankle and foot were evaluated in this report; 20 patients in this report had at least one tendon injury.2 (3700/65 msec-TR/TE), 15 cm FOV, 3 cm slice thickness, time of scan for each plane was 2.30 min. ADC mapping was acquired from one of these b-values with higher image quality. All MRI acquisitions were performed in the radiology departments of hospitals.MRI and DWI studies were performed on a 1.5 T MR scanner  by using an 8-channel standard transmit receive extremity coils with a linear configuration. Patients were laid in a supine position, with the ankle placed in a mild plantar flexion. Our MRI protocol: T1 weighted imaging (T1W) spin-echo (SE) sagittal/coronal planes (400–500/15–25 TR/TE), slice thickness 3 mm with 0.5 mm gap interface, 12–16 cm FOV, 192x256 matrix size, duration of scan: 2.15/1.53 min. T2 weighted imaging (T2W) turbo SE with fat-saturation (FS) sagittal and axial planes (3650/75-TR/TE), echo train length 8–12, slice thickness 4 mm with 0.4 mm gap interface, 14–17 cm FOV, 256 × 256 matrix size, imaging time: 2.40 min for each plane. PD-FS-coronal plane (2650/30-TR/TE), echo train length 6–10, slice thickness 4 mm with 0.4 mm gap interface, 15–17 cm FOV, 256 × 256 matrix size, and imaging time: 1.55 min. DWI and ADC mapping were performed by echo-planar spin echo imaging with 3D acquisitions, mostly by axial images as transverse planes were best to evaluate structural abnormalities of tendons with b values 400–600-800 s/mmTwo musculoskeletal radiologists analyzed the MRI images of ankle and foot together; a senior radiologist with 15 years’ experience and a special radiologist with 10 years’ experience. These MRI sequences and images were evaluated after the analysis of routine radiographs and there was no disagreement in the interpretation of the MR images. Two to three days later, both radiologists reviewed DWI-ADC mapping studies on separate work-stations independently and any disagreement was resolved by means of consensus, reviewers were blinded to patients’ data, clinical history, and surgical results, but were aware of the outcomes of prior MR sequences regarding the injured tendons. Both readers evaluated all DWI data in a random patient case order, quite different than the order of the MR images in order to overcome the potential bias for the interpretation of both sequences and not to cause any disadvantages for the real potential of DWI to diagnose tendon injuries. Senior radiologist with 15 years’ experience and senior orthopedician together determined whether the ankle MRI met the inclusion criteria of the patients belonging to this study. This senior radiologist also conducted each session of the evaluation trials. There were 2 sessions with one trial for each, both for MRI and for DWI evaluations; in total, 4 sessions with 2 trials were applied for both observers.Inter-rater reliability  is the degree of agreement among independent observers who rate, code, or assess the same phenomenon. In contrast, intra-rater reliability is a score of the consistency in ratings given by the same person across multiple instances. In other words, reliability of a measurement refers to the consistency of the data when the same trait is measured by the same observer (intra-rater reliability) or by different observer’s (inter-rater reliability) with the same measurement device ,19,20.It is very important to establish inter- and intra-observer reliability when conducting observational research, it refers to the extent to which two or more observers are observing and recording behavior in the same way .In order to calculate inter-rater reliability, each session was carried out by the observers’ on the same day of the MRI and DWI evaluations. Achievement of the equal conditions for both observers during the experimental evaluation was assessed by offering them almost the same workstations with similar properties independently and if present, by solving the problems with consensus. As a 2–3 day interval was taken for DWI analysis after the interpretation of the MR images, this period was used to assess intra-rater reliability on the same day for both observers due to their high diagnostic performance rate on that day in the evaluation of all images. In other related studies in the literature in which those procedures were applied, time interval ranged from 1 to 2 h/week for 1–2 months in order to ensure proficiency with the MRI and/or USI ,22. We dT; fluid of tendon sheaths with less than 5 mm width was regarded as simple sheath effusion and was not involved in this research [PT [R [All tendon injuries were named as Rupture or Complete tear (R), PT, and T. Thickening of tendons, >6 mm for A and >3 mm for other tendons with convex bulging of their anterior margins, without any intratendinous high signal on T2W and DWI and without any disruption/retraction or discontinuity and fluid of tendon sheath with more than 5 mm width, was recorded as research ,11,12. Tarch [PT ,12. Comph [PT [R ,12,13.In the Scanning Electron Microscopy (SEM), most of the collagen fibrillar bundles ran straight and parallel to the long axis of the stretched tendons: flattened and partially crimped bundles were recognizable in only a few segments, in terms of PT of tendons; completely straightened collagen fibrils with residual knots corresponding to ‘fibrillar crimps’ with flattened and totally stretched crimps, in terms of R of tendons; and collagen fibril bundles arranged in a crimp pattern with a sharp top angle with fluid accumulation through the tendon sheath, in terms of T of tendons .General information about the T, PT, and R, defined in the above paragraph, were considered to be the reference values to test the diagnostic accuracy of imaging approaches. Only injured tendons were included in the research; however, both observers defined 1 T case as normal/healthy tendon. All measurements of DWI were performed from the longest diameter. Open surgery was performed for 9 ruptured tendons, diagnostic arthroscopy and splint application were performed for 41 tendons with PT. Diagnosis and treatment of T of 31 tendons were based on physical examination, conservative therapy, and follow-up splint or bandage application. Conservative treatment included bed rest, non-steroidal anti-inflammatory drugs, and stretching. Corticosteroid injections were rarely used.All arthroscopic procedures were performed by a 15-year-experienced orthopedic surgeon and four of his team-mates . Through the 81 injured tendons, 50 tendons with R and PT used the surgical approach as the reference standard (62.5%). None of the patients in R and PT groups refused the arthroscopy. Six patients in T group refused the splint application and all other T group patients were treated conservatively; those six patients were not excluded from the study.t-test with p value, sensitivity, and the specificity ratios of both modalities—positive/negative predictive values were also additionally calculated by this test, with regard to arthroscopy as the reference. Comparison of DWI and MRI results of both readers against surgical results were performed by Pearson chi-square test. For all tests, p < 0.05 was considered to indicate a statistically significant difference. Pearson chi-square test was the gold standard test for the evaluation of DWI and MRI results of both readers.Statistical analysis of this research was performed by SPSS 25 written form . This analysis compared the independent DWI and MRI results of both readers and the common observers list with consensus, intra and interobserver variability for all injuries were calculated by variance analysis test with Kappa (k) values, Cohen’s κ model weighted kappa, regarding the consensus of DWI. k values more than 0.80 indicated perfect agreement, k from 0.6 to 0.8 presented high agreement, k values between 0.4 and 0.6 indicated moderate agreement, and k values of 0.2 to 0.4 presented fair agreement ,10. CorrAs the inter/intra-observer variabilities were tested and had statistically valuable importance to this article, the confidence level of each rater was considered to be a new diagnostic modality for the tendon injuries. Therefore, ROC curves were fitted to reveal the sensitivity and specificity of DWI and MRI more precisely with regard to those confidence levels and diagnostic performances of both observers, which were estimated by using area under this curve (AUC). Sensitivity and specificity ratios were also plotted under this area by using ROC curves.T  were involved in this research. Eighty-one tendon injuries and sprains were analyzed statistically. For R of EDL, FHL, PT, and A; T of EHL, FDL, FHL, PT, and TP; and for the PT of all tendons except TA and TP, both observer’s independent results were all similar with high agreement, had a significant statistical relationship with each other and with the common DWI list, and were correlated with each other and with the common DWI list . This was also proved statistically for the injured PT and FHL tendons with regard to the independent results of each reader, and correlated to the common DWI findings with moderate to high agreement  [p > 0.05, k: 1.00) , 41 partially torn tendons , and 31 tendons with 5–0.714) ,25. Six k: 1.00) . As therR, T, and PT of EDL, EHL, FDL, TP, and TA, there was no statistical correlation for each reader’s results to the common DWI list (p > 0.05). For R, T, and PT of FHL and PT, findings of both readers had a significant statistical relationship correlated with the results to each other . Results of both readers for other injured tendons did not present any statistical relationship to each other with high to perfect agreement  (For 547–1.2) .p < 0.05, k: 0.609). MRI sensitivity ranged from 50 to 89% for all tendon injuries  with almost 100% specificity for the R, T, and PT of all tendons. In this research, MRI showed highest specificity for the diagnosis of all injured tendons. Regarding the R of nine tendons , there was no statistical correlation for each of the tendons separately, and DWI had 100% sensitivity and specificity for the diagnosis of all ruptured tendons without any statistical differences against the surgical approaches with perfect agreement . DWI had 100% sensitivity and 90% specificity for the visualization of 41 tendons with PT, and 100% sensitivity and 83% specificity for the evaluation of 31 tendons with T, by certain agreement and with a significant statistical relationship over the gold standard, arthroscopy, and physical examination  [MRI depicted all tendon injuries with 70% sensitivity and 100% specificity, and had significant statistical correlation to the surgical arthroscopic references with high agreement (0–0.899) ,25.p < 0.05, k: 0.875–1.00). Except for the T of FHL tendons (100% sensitivity and 67% specificity), all other PT and T of tendons were diagnosed by DWI with perfect agreement and 100% sensitivity/specificity, without any statistical approval over the gold standard or diagnostic arthroscopy  [For 16 PT of FHL tendons and 15 PT of PT, DWI had 100% sensitivity for both tendon injuries, 88% specificity for FHL, and 100% for PT with high to perfect agreement and a significant statistical relationship to the reference (k: 1.00) ,25   was also found. DWI had also statistical superiority over MRI, with fair to moderate agreement for the evaluation of T of FDL, and PT of FHL and PT . Sensitivity of DWI ranged from 50 to 100% and specificity from 12.5 to 100% for the visualization of EDL, EHL, and TP injuries with fair to perfect agreement without any statistical dominancy over the MRI   , and the2–0.459) a–d. DWI 20–1.00) .When we evaluate the results of both readers by the ROC curve, R of tendons had an AUC value: 0.875 ± 0.141, with 100% sensitivity and specificity for both readers. Sensitivity remained constant (100%); specificity ranged from 25 to 100% for the AUC values between 0.500 and 1.000. PT of tendons had an AUC value 0.734 + 0.080, and 100% sensitivity and specificity were found for both readers, by AUC value: 0.500, 91.7% sensitivity, and 44.8% specificity were predicted. Sensitivity ranged from 91.7 to 100% and specificity between 44.8 and 100% for both readers with AUC values between 0.500 and 1.000.AUC value for T of all tendons was 0.699 + 0.116 and from this value to AUC: 1.000, indicating 100% sensitivity and specificity. AUC value: 0.500, presented 95.5% sensitivity and 55.6% specificity for both readers. Sensitivity ranged from 95 to 100%, specificity ranged from 55 to 100% between these AUC values for both readers .The first reader had one and the second reader had two false negative results for the R of tendons. Both readers had twelve false negatives for PT of tendons. The first reader had nine and the second reader had five false negatives for the T. Both readers had no false positives for ruptured tendons. For PT of tendons, the first reader had six, and the second reader had eight false positive results. For the T, the first reader had seven, and the second reader had three false positive yields.Conventional ankle MRI has been widely used for the assessment of all ligament and tendon injuries, and it has also used to differentiate tendon abnormalities from other causes of ankle pain, such as occult fractures, bone contusions, osteochondral injury, etc. ,26,27,28There were numerous reports in the literature regarding the ankle MRI. Most of the presented reports were about A tendon injuries: Marcus et al.  declaredDWI allows quantitative measurement of the motion of water molecules into the lesions and normal tissues, net diffusion of water molecules is referred as the ADC, and it combines the effects of capillary perfusion and water diffusion in the extracellular space ,35,36,37Achilles tendon exploration by diffusion tensor imaging, post-operative Achilles tendon examinations by MRI-US, and rotator cuff tears imaging by DWI were relevant in the literature, but, for our purposes, this report was the first in the literature concerning the efficacy of DWI in the diagnosis of tendon injuries in the ankle and foot ,43,44,45We thought that DWI theoretically might supplement relevant data beneath the routine MRI, via presenting the motion and diffusion of water molecules through the diseased tendons, showing the accumulated effusion within the tendon sheath plus peritendinous areas, and supplying a good-contrast between the injured tendons and normal surrounding soft tissue. In our view, these contrast differences in the imaging approaches, revealing the diseased tendons, probably supply the most important data for clinical practices, and this was the crucial point of this research. MRI presented 83%, DWI had 100% sensitivity for the evaluation of A injuries, and both imaging modalities had 100% specificity for this injury. Nevertheless, DWI was more sensitive than MRI for the depiction of A rupture without any statistical superiority, so surgeons should not simply use DWI for clinical diagnosis of A tendon disorders; however, with respect to whole ruptured tendons, DWI had significant statistical superiority over MRI in this report.R of A, T of FDL, PT of FHL, and PT 80–100% sensitivity for PT of FHL, and PT with 55–64% specificity and 88% sensitivity for the T of FDL, as observed by DWI. These were quite satisfactory results and, to our belief, could easily influence the results of a routine MRI, and might aid in the treatment planning of clinicians and surgeons. This research also demonstrated that DWI was more valuable than routine MRI for the depiction of ruptured tendons. With regard to arthroscopy, DWI had 100% sensitivity for all injured tendons and presented 67–100% specificity for the diagnosis of them.DWI predicted superiority to ankle MRI for the evaluation of R, PT, and T of all tendons with more than 90% sensitivity and about 50% specificity over MRI. This was mostly due to the visualization of MRI regarded 70% sensitivity (50 to 90% range) and 100% specificity for tendon injuries, significantly less sensitive than DWI; thus, we can easily declare that routine MRI protocol of ankle and foot was not enough for the entire diagnosis of tendon injuries, especially for PT and T. Additional imaging techniques such as DWI could aid in the diagnosis, supply more beneficial and relevant data for the depiction of injured tendons, and could also be included in the routine ankle MRI for more appropriate evaluation.Limitations of this research were: T was about 37.5% of all injuries; these were diagnosed and treated conservatively so there was no surgical proof regarding the less relevant results. We did not adopt contrast-enhanced scans in the routine ankle MRI as this might have created some mis- or overdiagnosing tendon injuries. We did not include a control group because it was very difficult to create a strict control group with individuals who had never had an ankle injury. Finally, DWI had lower spatial resolution with low image quality, this might have therefore presented some problems for the visualization and diagnosis of tendon injuries.In conclusion, DWI with a duration of scan about 5 min, with acquisition in two planes, might further improve the sensitivity, specificity, and accuracy of classical ankle and foot MRI, and might strengthen the clinicians’ and surgeons’ profiles for the treatment options of patients. With regard to the yields of this report, DWI revealed additional diagnostic information about the injured tendons, especially for PT and T.


Takayasu's arteritis is a rare form of chronic inflammatory disorder involving large vessels, with an unclear etiology. Common early signs and symptoms are weakness, malaise, and fever. Takayasu's arteritis mainly involves the aorta and its branches as well as the subclavian and carotid arteries. While radiologic methods can identify diseased vessels, they can't tell the difference between active and chronic lesions. This study reviews the characteristics of Takayasu's arteritis to identify any possible changes in the prevalence of symptoms of the disease.R. RStudio, PBC, Boston, MA).We conducted a literature review of case reports on Takayasu arteritis from PubMed and Google Scholar. Variables of interest were age, gender, symptoms, blood pressure (BP) measurement, diminished pulses, and radiological findings. Data were transferred to an Excel spreadsheet , and mean, median, and standard deviation, frequencies, and proportions were calculated using R version 1.1.456 , followed by chest pain (13.95%), claudication (13.95%), and headache (13.95%). Less frequent complaints included shortness of breath (11.62%), weight loss (9.30%), syncope (6.98%), and night sweats (4.65%). On the right side, the average BP was 142/87 mmHg, and the left-sided finding averaged 115/72 mmHg. Decreased pulses were primarily seen in the radial artery with 15 cases. Radiological findings showed narrowing of the vessels in the following order: aorta (22), carotid (11), renal (10), subclavian (9), celiac (2), mesenteric (2), axillary (2), and tibial (1).The characteristics of Takayasu's arteritis were analyzed in this study. It identified several findings, ranging from fever symptoms to the signs of claudication, as well as the involvement of major vessels, such as the aorta and its branches, and a summary of radiological findings. This depicts the picture of Takayasu's arteritis and what physicians should expect when dealing with the disease. Takayasu arteritis (TA), often known as pulseless disease, is chronic inflammatory arteritis characterized by damage to the medium and large arteries as well as their branches. The aorta and its primary branches, particularly the renal, carotid, and subclavian arteries, are commonly affected, resulting in stenosis, occlusions, or aneurysmal degeneration of these large vessels . DespiteMethodsEligibility CriteriaAll case reports published on the Internet under the name Takayasu arteritis.Search StrategiesA systematic search of Takayasu arteritis case reports utilizing Google, Yahoo, Medscape, Scopes, and Cochrane, and scientific databases such as Google Scholar and PubMed.Data Collection Process and Data ItemsUsing standardized data extraction forms, data were extracted independently by two authors. We collected characteristics like age, gender, initial symptom presentation, laboratory values, vital signs, diagnostic imaging, and echocardiography results on an Excel sheet , and these variables were analyzed.Statistical AnalysisPatient demographic characteristics, disease manifestations, and causes were summarized descriptively and analyzed using R version 1.1.456 .ResultsWe reviewed 43 case reports available online and gathered all the data regarding the characteristics and presentation of initial symptoms. Table The average age of the population is 25 years, with a standard deviation of 12.5 years. Females accounted for 88.3% of the cases while males accounted for 11.6 %. The most common symptom of Takayasu arteritis was fever (20.93%), followed by chest discomfort (13.95%), claudication (13.95%), and headache (13.95%). Shortness of breath was reported in 11.62% of cases, weight loss in 9.30% of cases, syncope in 6.98% of cases, and night sweats in 4.65% of cases. Out of all the collected data, 15 cases reported absent or decreased pulse in the radial artery with five cases of brachial pulses. A case of an absent pulse of the subclavian, carotid, femoral, and dorsal arteries was also reported. In 6.97%, there was a bruit, and in 6.98 % of cases, there was a murmur. We noticed the following vessels implicated on imaging stated in case reports . Both illnesses cause arterial wall changes that are similar in appearance such as chronic inflammatory lesions, and, in rare cases, granulomas of large and medium vessels . DespiteIt's now assumed that an unknown trigger causes the 65kDa heat-shock protein to be expressed in aortic tissue, which subsequently causes the major histocompatibility class I chain-related A (MICA) to be expressed on vascular cells. T cells and NK cells with NKG2D receptors recognize MICA on vascular smooth muscle cells and release perforin, resulting in acute vascular inflammation. Th1 lymphocytes release interferon-, which causes giant cells to form and activate macrophages by releasing vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), which cause neovascularization and smooth muscle migration and intimal proliferation, respectively. The IL-23 microenvironment promotes the recruitment of infiltrating neutrophils by Th17 cells, which adds to vascular lesions. Dendritic cells and B lymphocytes can work together to stimulate the production of anti-endothelial cell autoantibodies, resulting in complement-dependent cytotoxicity of endothelial cells, however, this is still debatable . The greBased on the more prevalent symptoms, the American College of Rheumatology (ACR) adopted precise diagnostic guidelines for Takayasu's arteritis in 1990. At least three of the six criteria must be met to diagnose Takayasu arteritis Table  11]..11].Takayasu arteritis has a wide range of clinical symptoms, ranging from asymptomatic disease induced by impalpable pulse or bruits to serious neurological impairment. Non-specific symptoms include fever, night sweats, tiredness, weight loss, arthralgia, myalgia, and mild anemia . As the For medical management, steroids are the mainstay of treatment for Takayasu arteritis. Steroids have a 50% response rate, and methotrexate, which has a 50% response rate, are the best evidence-based therapy. Methotrexate's use as a steroid-sparing medication is both reasonable and safe. Twenty-five percent of patients with active disease will not respond to existing treatments, and it is important to avoid exposing these patients to the risks of extended immunosuppression in the lack of other options. Another key medical issue is the use of steroids, particularly in patients with critical hypertension, because hypertension is difficult to manage and is exacerbated by the use of steroids, which have fluid-retaining adverse effects .Hypertension with critical renal artery stenosis, extremity claudication limiting daily activities, cerebrovascular ischemia or critical stenoses of three or more cerebral vessels, moderate aortic regurgitation, and cardiac ischemia with confirmed coronary artery involvement are all indications for surgery . In geneThere is a classification depending on vessel involvement that can aid in planning surgery and may provide a prognosis Table  17]..17].Takayasu arteritis is a relatively uncommon condition that can manifest itself in subtle and insidious ways. Nonetheless, prompt diagnosis is essential since failing to treat vascular inflammation in a timely manner might have serious consequences for the patient. There are two categories of symptoms that can alert a clinician to the presence of Takayasu arteritis: A systemically unwell patient with nonspecific laboratory results pointing to inflammatory disease. Cardiovascular features, such as claudication of the limbs, hypertension, arterial pain, and distal cutaneous hypothermia, especially in a young patient or one who does not have atherosclerosis risk factors .The characteristics of Takayasu's arteritis were investigated in this study. Several physical findings and their corresponding values, as well as a summary of radiological findings, have been listed. Based on the review and analysis of all the case reports on Takayasu arteritis, we observed that Takayasu arteritis is most commonly seen in females, with an average onset age of 13-38 years. The majority of patients present with a wide range of symptoms, from fever to signs of claudication and the associated symptoms. The results showed the difference in blood pressure measurements of two distinct limbs with a decreased or absent pulse, primarily radial pulse. Takayasu could be a differential in symptomatic patients with high ESR and CRP levels. The main entity for diagnosis is imaging, which depicts stenosis of major vessels and other conditions. Because of the clot formation, there may be some changes in heart function as well as related consequences. This paints a picture of the landscape of Takayasu’s arteritis and what physicians should expect when dealing with the disease.