The skin is constantly exposed to external and internal factors that disturb its function. In this work, two nanosystems-levan nanoparticles and a surfactin-stabilized nanoemulsion were preserved  and characterized . The nanosystems were introduced in the model formulations-cream, tonic, and gel, and confirmed by TEM. The analysis showed that nanoemulsion has a spherical morphology and size 220–300 nm, while levan nanoparticles had irregular shapes independently of the use of matrix and with particle size (130–260 nm). Additionally, we examined the antiradical effect of levan nanoparticles and nanoemulsion in the prototype of formulations by scavenging DPPH . The model cream with both nanosystems and the whole range of products with nanosystems were evaluated in vivo for hydration, elasticity, smoothness, wrinkles and vascular lesions, discoloration, respectively. The cream improved skin condition in all tested parameters in at least 50% of volunteers. The use of more comprehensive care, additionally consisting of a tonic and gel, reduced the previously existing skin discoloration to 10.42 ± 0.58%. The presented prototype formulations are promising in improving skin conditions. The topical route of administration has many advantages for the treatment of various skin disorders as well as cosmeceutical purposes . The demIn the past few years, applied nanotechnology has received increasing attention in pharmaceutical, food, cosmetic, textile, personal care, agricultural, chemical, biotechnology, biomedical, and sensor industries. Colloidal carrier systems are advantageous in solubilizing poorly soluble active substances . BiologiMost cosmetics are applied topically. Therefore, an important aspect is the penetration ability through the skin barrier. The external layer stratum corneum is an obstacle to the penetration of active substances, especially hydrophobic. Due to encapsulation, hydrophobic compounds are easier to deliver to the deeper skin layers . EncapsuBacillus subtilis and is one of the novel components which might improve skin condition. Levan provides deep and long-lasting skin hydration due to its porous structure. It is non-toxic to human fibroblasts and keratinocytes and has no hemolytic effect on erythrocytes. Our previous research has also shown that it has antioxidant properties [One of the more desirable effects is skin hydration. For this purpose, nano-systems composed of moisturizing substances are used. One of the most commonly used moisturizing substances in cosmetics is hyaluronic acid (HA) . Howeveroperties . Despiteoperties . Both ofoperties .B. subtilis, is a naturally derived surfactant (biosurfactant). It is a cyclic lipopeptide with high surface activity, and at the same time, it is biodegradable. Surfactin is non-toxic to healthy cells, including the keratinocytes HaCaT cell line and has anticancer properties [It is also very important to provide nutrients, the nanoemulsions are perfect as nanocarriers. Composed of a suitable surfactant, they ensure the formation of small vehicles with a bioactive substance inside . The useoperties . The ideThis research aimed to incorporate two types of nanosystems–levan nanoparticles (NP) and nanoemulsion (NE) stabilized by surfactin–in the three topical formulations. Model formulations of tonic, gel, and cream were chosen for incorporation during the production process in matrix single and hybrid double dispersion. Firstly, preservatives have been tested, and their effect on the stability of the systems has been examined. Additionally, the results have been confirmed by the DLS method. Change in the size of drops, the zeta potential of the dispersion, and polydispersity were measured. All formulations were compared to each other in antiradical properties by radical scavenging EPR technique, analyzing the synergistic effect of nanosystems with matrices. The incorporation of NP and NE has been confirmed by imagining by TEM. In the end, the skin condition was assessed using the analyzer: structure, hydration, pore size, depth of wrinkles, degree of discoloration, and the properties were confirmed by ten women, aged 42– 54 years, using the preparation.The main task of the preservative is to keep the product-during storage and use-in the same microbiological purity in which it was produced. The addition of preservatives also prevents the formation of microbial metabolic products, which can cause skin irritation. Preparations of products, especially those that contain a large amount of water, are prone to the growth of microorganisms . As a reOur work aims to incorporate nanoemulsion systems and nanoparticles of levan into cosmetic matrices. These systems, dispersed in water, are introduced into more complex matrices in which the main component is water. Therefore, the first step was to select an appropriate preservative for nanosystems. In the case of preservation of nanocarriers, antimicrobial agents should not affect their stability as well. Preservatives are known for causing physical instability of disperse systems such as aggregation, coalescence . The firPivotal role during selection was driven by their chemical performance: hydrophilic , and hydrophobic  . AdditioAfter selecting the appropriate preservatives for the nanoemulsions, the next step was to check whether any of the typed preservatives would also be stable and have antimicrobial effect on the solution of levan nanoparticles. Since levan nanoparticles are considered to be stable systems, stability tests were narrowed regarding temperature, as well as the number of tested preservation systems . Among 1In nanosystems, it is not always possible to see the symptoms of aging, instability, or aggregation. Hence, an important element is the DLS analysis. It allows determination of not only the size of a given carrier but also their polydispersity and the Zeta potential. Analysis of those parameters may indicate their stability. The most desirable PdI value is around 0.2. However, in the case of the Zeta potential high values indicate high stability of the carrier, which is important during the manufacturing processes. Samples of nanoemulsions after preservation with previously selected antimicrobial agents for further tests were tested by means of DLS analysis . ShortlyThere were also changes in the polydispersity of these samples, but they are still very optimal and close to 0.200. Changes resulting from the stabilization of the systems were observed with regard to the Zeta potential.E. coli, S. aureus, and yeast C. albicans. The initial number of microbial cells in the inoculum and 1g of the tested formulation is given in Preservation systems that gave satisfactory results after DLS measurements were subjected to preservation efficacy test, so-called challenge test. There were 12 antimicrobial agents tested for their protection efficiency . NanoemuPentylene glycol, by itself or combined either with phenylpropanol or with citrus extracts meet the criteria given in Levan nanocarriers are prone to microbial deterioration since they are of bacterial origin. Preliminary tests, consisting of a simple microbial purity check, showed, that out of 13 tested preservatives, only one was effective to suppress bacterial growth, and further was examined for its preservation efficacy. Antimicrobial agent composed of glycerin and propylene glycol (AA) turned out to be effective during a challenge test  and the The ingredients used in cosmetic products depend greatly on the type of formulation . However, the principal raw materials used to manufacture cosmetics are water, oily materials, fats, and wax, surfactants, humectants, thickening agents, antioxidants, preservatives, coloring agents, along with vitamins, as well as active agents. Cosmetic emulsions based on vegetable oils are the subject of many studies reported in the literature. They are preferred instead of mineral oils, due to their characteristics: biocompatibility and biodegradability, effectiveness in protecting the skin against solar radiation, inflammation, insect attack, microorganisms, and viruses . Moreove® Care PSC 3-Evonik) was used. It is a non-ionic emulsifier, obtained in the process of esterification of polyglycerol-3 with stearic acid and citric acid. This emulsifier has a good emulsifying effect and good skin tolerance. Polyglyceryl-3 dicitrate/stearate in combination with consistency-forming ingredients, such as glyceryl stearate and cetearyl alcohol, creates emulsions building lamellar structures. This emulsifier is adapted to emulsions, in which it works synergistically with the natural organic acids used.The cream’s composition has been developed exclusively based on natural ingredients. The cream has been specially designed in such a way as to take into account all aspects, both technological, application, and safety-related. The prepared recipe is an O/W emulsion. When developing a recipe, the ingredient necessary to create an emulsion is an emulsifier. The emulsifier polyglyceryl-3 picitrate/stearate  butter, squalane, sesame oil, oleic/linoleic/linolenic polyglyceride, caprylic/capric triglyceride, octyldodecanol emollient, triheptanoin. They are all characterized by great skincare properties.To provide the emulsion with appropriate sensory properties and better distribution, the following emollients were used, such as As for substances that increase and control the condition of skin hydration, propylene glycol, and glycerin were used. Thanks to the ability to penetrate the stratum corneum, glycerin acts as a promoter, making it easier for active substances to penetrate deep into the skin. It homogenizes cosmetic ingredients and is also a humectant with gentle preservation properties. Propylene glycol, vegetable glycol, is an excellent carrier of active substances and a solvent for acids and plant extracts. Thanks to a small molecule, it easily penetrates deep into the epidermis, improving its hydration level.Punica Granatum fruit extract. Tocopherol is an antioxidant. It protects cosmetic products, including oils, against oxidation. The Punica Granatum fruit extract helps protect the skin from damage by free UV radicals. It contains large amounts of polyphenols, including anthocyanins, gallotanin, and ellagitanin with strong antioxidant and astringent properties. In addition, substances increasing the viscosity of the entire formulation were used, such as microcrystalline cellulose and xanthan gum, as well as the preservatives benzyl alcohol, benzoic acid, and dehydroacetic acid.The cream also contains two ingredients from the group of active substances-tocopherol and The serum components have been selected in a way to facilitate the penetration of active substances. Permeation promoters are a mixture of natural glycols (propylene glycol and pentylene glycol). These substances also improve the condition of the skin.One of the ingredients of the tonic is betaine. It has a protective effect on cell membranes and has a soothing and moisturizing effect. Another ingredient is sodium L-pyroglutamate-it is present in the skin as a component of NMF , which allows water to be retained in the stratum corneum. It is one of the most effective moisturizing factors. It permanently moisturizes the epidermis and deeper layers of the skin softening it and toning. Another active ingredient is aloe vera juice, which has a strong moisturizing, softening, and antioxidant effect. It also has anti-inflammatory properties and speeds up wound healing.−1) and the presence of alcohols like glycerol, propylene glycol (hydroxyl group oscillations ~1500 cm−1). In the case of cream, there are also characteristic bands associated with aliphatic groups from fatty acids (~2900 cm−1) [The IR analysis shows that there are no spectral differences between empty formulations and formulations enriched with levan nanoparticles or nanoemulsion . This ob00 cm−1) . Transmission electron microscopy (TEM) is the rapid, powerful, and relatively non-invasive visual technique to obtain information about the mean size and the actual surface and morphology characteristics of the prepared and incorporated nanosystems in the matrix. Imaging was performed for all three prototype formulations with the incorporation of two types of systems .The TEM photographs revealed that nanoemulsion was of spherical morphology having diameter range from 220 nm to 300 nm, and levan nanoparticles show a deformation from a spherical form, appearing in irregular shapes independently of the matrix used and with particle size 130–260 nm. The diameter of NE and NP-levan obtained using DLS  and TEM Due to the capability to oxidize lipids, proteins, and nucleic acids, free radicals are one of the skin aging factors. Hence, radical scavenging is an essential property of cosmetic formulations . MoreoveAt first, the antiradical potential of levan nanoparticles, nanoemulsion, and their linkage in three different formulations  were investigated. The samples were measured 30 min after adding the DPPH solution. These results showed us that in all formulations free radical scavenging effect is observed . Empty fSterculia populifolia extract as an antioxidant [In the case of tonic and serum, the scavenging of free radicals was moderate, but the cream showed much greater properties in removing them. Moreover, in all three formulations, a synergy of nanoemulsion and levan nanoparticles linkage was observed. Such an effect was described also in other systems . Due to ioxidant . Its autioxidant , hence iCosmetic preparations for application on the skin  are designed to protect the skin, remove its small defects, such as by smoothing wrinkles or whitening discoloration. However, for these processes to take place, the active substances contained in the cosmetic must penetrate the deeper layers of the skin. The use of nanosystems enables the transport of active substances and may support skin repair processes. Application tests carried out on volunteers using non-invasive methods are one of the possibilities of testing preparations before their commercialization . In thisIn the case of elasticity, both creams had a similar effect, but the one containing levan and nanoemulsion was 1.1% more effective  B. The reAfter using the cream with levan and the formulation, the volume and area of wrinkles decreased by 2.3 and 3.2%, respectively (where for the base cream the parameter improved by 2.1 and 2.8%) . In the 2, and after 28 days of use, 1.41 ± 1.28 mm2. For the products with nanosystems, this value was 2.27 ± 0.95 mm2 before application, and after 28 days of daily applications, 1.37 ± 1.16 mm2. In the case of discoloration, it was found that the base cream did not reduce the discoloration on the skin after 28 days of use, unlike the cosmetics with nano-systems. Initially, the discoloration was 10.91 ± 3.20% and 10.88 ± 0.72%, and after 28 days of use, it was 11.29 ± 0.79 and 10.42 ± 0.58%, respectively for the base cream and cosmetics with nano-systems. Sample of changes before applying the formulation and after 28 days of use in Based on skin analyzes carried out with the use of NatiV3, the effect of the cream, serum, and tonic with two nanosystems on vascular lesions and discoloration was determined. Comparing the base cream with the range of products with nano-systems, their effect on the vascular lesions was negligible. The values for both tested versions of skincare are similar to each other, and additionally, they are burdened with quite a large standard deviation. For the base cream, the size of the vials was 1.87 ± 1.28 mmThe analysis of a given preparation is difficult to interpret. The skin is not a homogeneous tissue and it is characterized by high variability in parameters, even within one examined person. The skin’s reaction to a given cosmetic also depends on the state of health, environmental conditions, etc. The developed preparation with a double nanosystem is only at the initial stage of research. Further work is underway to improve it. The studies conducted so far have shown that their use in cosmetic preparations has a positive effect on the condition of the skin. The use of polymers in the production of cosmetics is very common. Their addition has a great influence on the consistency of the preparations, increasing their viscosity and ensuring greater stability of the emulsion. The addition of more than one polymer can lead to faster coalescence or isolation of the emulsion droplets. The use of polymers in cosmetics also affects their care properties. They can retain water in their structures, thus increasing skin hydration. The polymers can also form a scaffold for other essential ingredients, e.g., ions, or form a coating around sensitive active substances. The use of bacterial cellulose in cosmetics include facial masks, facial scrub, personal cleansing formulations, and contact lenses has been reported so far . AnotherBacillus subtilis natto KB1, described below. Levan standard was purchased in Sigma-Aldrich . All medium components were purchased from BioShop LabEmpire . Ethanol and minerals were purchased in Chempur . All other reagents were of analytical grade and used as provided. Water used for all experiments was doubly distilled and purified through a Milli-Q water purification system .Nanoparticles of levan were prepared with a precipitated and lyophilized polymer. An appropriate amount of levan was taken to prepare a 5% solution in distilled water. It was stirred till it dissolved. Then the solution of levan nanoparticles was incorporated into the cream. Levan was obtained from microbial fermentation with Bacillus subtilis natto KB1 was grown at 37 °C for 24 h with continuous shaking in a 5 L bioreactor. After 24 h, the culture was stopped and centrifuged to separate the bacterial biomass. Levan was separated from the supernatant as described before [The culture of d before .Nanoemulsion concentrate was prepared as follows: 50% of sodium surfactin powder, 30% of 2-(2 ethoxyethoxy) ethanol  and 20% of ascorbyl tetraisopalmitate  were subjected to ultrasound for 20 min, at 50 °C, as previously described . ConcentB. subtilis natto KB1, as described before [Surfactin was obtained from microbial fermentation with d before ,43. All Following ingredients were obtained as a gift: Dermosoft PEA, Dermasoft GMCY, Dermosoft 1388 Eco , Activonol BG , Stabil Zero, Kem Nat, Kem Nat Beta, Kem DH , Liqupar ME , Cosphagard Elbe, Cosphagard Pol, Cosphaderm LA-T, Cosphaderm TOM, Cosphaderm Hexiol, Cosphaderm Octiol, Cosphaderm Sodium LAAS , InBioLev, InBioSur , Geogard ECT, Geogard Ultra , E-Leen Green OR, MinaSolve Green A, A-Leen Aroma-3 , Euxyl PE 9010, Euxyl K340, Euxyl K320 , Sharomix 703 . Other raw materials were purchased, Ajidew NL-50 , Viamerine 2500 , Aloe Vera SDP 200X , Myritol 312, Eutanol G, Cetiol SB 45, Lanette O, Cutine GMSV, Plantacare 810 , Propylene Glycol , Cosphaderm 1,3 -Propanediol, Cosphaderm X34 , Glycerin , Fruitliquid Pomegranate , Dermofeel PA 12, Tego Natural Betaine, Tego Care PSC-3, Dermofeel Toco 70 non, Dermofeel PA-12 , Transcutol HP , Sesame Oil , Miglyol T-C7 , A-Leen 5 , Nikkol VC-IP , Vivapur CS 032 XV , Natural Parfume , Euxyl K903, Euxyl K903 , Sharomix 713 , Phytosqualan .2 (UVA). After every month of incubation, microbiological tests for the presence or absence of mesophilic microorganisms as well as for yeast and molds were conducted as described in Obtained nanoemulsions were subjected to various preservation strategies. Homogenization of nanoemulsions was followed by the addition of antimicrobial agents according to Escherichia coli (ATCC 8739), Pseudomonas aeruginosa (ATCC 9027), Staphylococcus aureus (ATCC 6538). The obtained results were assessed according to the criteria given in The preservation efficiency test was performed according to the method described in the normative document ISO 11930 . NanoemuH) and Z-potential measurements after preparation (D0) and 90 days (D90) of storage as well as dispersion stability test [The integrity of nanocarriers with preservatives was inspected organoleptically right after preparation (D0), after 30 (D30), and 90 (D90) days of incubation at three temperature conditions. pH was measured after preparation (D0) of all prepared nanocarriers and was continued in case of visual integrity. DLS measurements were taken in case of organoleptic acceptance to overcome the problem of unstable formulations, nanoemulsions were subjected to time-dependent size (Dity test . The formulation prototypes (new design) have been developed for this work. All the ingredients were carefully selected and used for the formulations according to the rules provided by The European Cosmetics Legislation . The maiPreparation:Phases A and B were heated separately to a temperature of 70–75 °C, which was followed by homogenization. Raw materials from phase C were added into the water at 40–45 °C and mechanically stirred for about 1 h. Phases A and B were poured into one vessel and subsequently phase C was added. Such a prepared mixture was homogenized. Afterward, the emulsion was cooled down by a mechanical stirrer at low speed. Phase D was added and pH was set to the value of 5.5 with citric acid. Previously prepared nanosystems (phase E) were mixed into the emulsion at the final step . The transmission electron microscopy (TEM) measurements were performed to measure the morphology and size distribution of lipid nanocarriers. Images were taken using an FEI Tecnai G2 20 XTWIN electron microscope . The size distribution of the nanocarriers for each sample was determined by counting the size of approximately 250 nanocarriers from several TEM images obtained from different parts of the TEM grids. A few drops of the diluted suspension were placed on the grid and stained with 2% uranyl acetate, and then the image was captured. The size distribution plots were fitted by using Gauss curve approximation.−1.Functional groups and chemical bonds of the obtained cosmetic products were determined using Fourier-transform infrared (FT-IR) spectroscopy on Spectrometer Bruker Vertex 70 FT-IR . The sample was prepared as a thin film. All of the samples were scanned over a wavelength range of 4000–400 cmAntiradical properties of self-assembly nanosystems incorporation in the different matrix were studied by radical scavenging activity using DPPH by electron paramagnetic resonance. A stable radical solution in ethanol was stirred in dark for 2 h to obtain a homogeneous solution. Next, the tested systems were prepared as follows: 75 μL of radical and 100 μL of the sample (5x diluted in water) were mixed. The capillary tube with the sample was sealed and placed inside a standard EPR quartz tube, then placed in the resonant cavity. Measurements were carried out at room temperature. Data were reported as the average of three measurements. The EPR spectra were recorded using a Bruker Elexsys 500 spectrometer operating at the X-band frequency (~9.7 GHz). A microwave power of 1 mW, modulation amplitude of 1 G, a sweep width of 200 G were adopted. An analysis of the EPR spectra was carried out using the WinEPR software package, version 1.26b . The double integral of the signal was evaluated as representative of the free radical concentration. The field under the absorption curve is proportional to the number of stable radicals remaining in the sample. The percent value of scavenged DPPH was calculated with the following formula:Isample—integrity of signal measured in the sampleIstandard—integrity of signal measured in the sampleFor in vivo evaluation of vascular lesions, discoloration, NatiV3 Analyzer  was used . The meaThe test was performed on 10 women, age 42–54 years. Measurements were taken on healthy skin, without irritation signs. Volunteers were advised not to use any antihistamines or pharmacological drugs, which could interfere with the results. Both formulations were applied daily, one without the addition of NP levan, and NE was applied on the left part of the face, neck, and neckline, while the formula with NP levan and NE on the right part of the body. The measurements were taken before the application of formulations, and after four weeks of application. All measurements were carried out in a room with a temperature of 20 °C and relative humidity of 50 ± 10%. Performed methods were designed in accordance with Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products; Cosmetics Europe-The Personal Care Association Guidelines Product Test Guidelines for the Assessment of Human Skin Compatibility 1997; Cosmetics Europe-The Personal Care Association Guidelines for the Evaluation of the Efficacy of Cosmetic Products 2008 and the laboratory procedure No. PB-19 ed. I from November 10, 2017 “Cosmetic products. Apparatus application research”.® CM 825, for firmness/elasticity–Cutometer MPA580, smoothening effect–Visioscan VC98, reduction of wrinkles–Visioline VL650. All the measurements were performed in triplicate . The obtained results are presented as absolute numbers.For the assessment of skin hydration, a Multi Probe Adapter System was used , which is connected to a probe used for the determination of the skin surface hydration-Corneometerp < 0.05 was considered statistically significant.All data are expressed as the mean value ± standard deviation of three measurements. Statistical analyses were accomplished using an online one-way analysis of variance with the post hoc Tukey honest significant difference calculator. A value of Antimicrobial agents were tested on the nanoemulsion and levan nanocarrier stability. For nanoemulsions pentylene glycol, 1.2-hexanediol and butylene glycol proved to have a preservation effect. In the case of levan nanocarriers, only glycerin combined with propylene glycol presented this effect. Systems with preservatives showed stability in 90 days and had a slight influence on the particle size. The incorporation of nanosystems into three prototypes of matrices was proved by infrared spectroscopy and microscopy imaging. Antiradical properties were evaluated by radical scavenging-EPR spectroscopy. The strongest synergy NP, NE, and matrix were observed in the emulsion. The effect was observed and confirmed by an application study. Cream tested on volunteers increased skin hydration, elasticity, and had a smoothening effect. In regard to wrinkles, it reduced their area and depth.


Short bowel syndrome (SBS) is a disorder characterized by malabsorption due to the absence or resection of a long small intestine tract, with an incidence of 2 per million of habitants. In adults, SBS is defined as less than 200 cm without colon and less than 50 cm with residual colon in continuity . The cauTeduglutide (TED) is a drug analogous to glucagon-like peptide 2 (GLP-2), recently approved for the treatment of adult patients with SBS on parenteral nutrition, with a dosage of 0.05 mg/kg subcutaneous injection once daily . CurrentWe report a case of a 65-year-old woman affected by a severe form of CD, diagnosed in 1991. From the beginning, the disease had an ileocolonic localization with a stricturing-fistulizing phenotype. Because of the extensive and aggressive disease, together with the lack of response to conventional and biological treatments , the patient underwent multiple abdominal surgical resections, the last one in 2010, with a final ileo-colonic anastomosis. Overall, the remaining gut was of about 110 cm in length. Thus, the patient developed a SBS, although she did not required parenteral nutrition.2. Due to significant electrolyte losses and recurrent metabolic acidosis, the patient underwent biweekly infusions of magnesium, potassium, and bicarbonate in addition to oral supplementation. Moreover, she was supplied with enteral nutrition, since oral nutrition resulted in worsening of the diarrhea.In November 2015, while she was under treatment with Adalimumab, she reported from 20 to 40 bowel movements per day with watery stools and progressive loss weight with a body mass index of 17 kg/mIn March 2016, after an ineffective attempt with octreotide, the patient was treated with TED 0.05 mg/kg daily, although the drug was approved only for patients with SBS on parenteral nutrition. However, after 24 weeks of treatment with TED, enteral nutrition was reduced by at least 50% and, after 72 weeks, it was suspended permanently. Moreover, intravenous infusions of magnesium and potassium were nearly abolished (i.e. once every 3 months). The patient, currently under treatment, is on oral feeding and is reporting four evacuations/day with formed stools. During treatment, the patient did not develop mild side effects, except for a diffuse abdominal pain and nausea, occurring only during the first week of treatment. No serious side effects were recorded during the whole period. Of note, the therapy markedly improved the quality of life of the patient, resulting in a normal social and private life.Symptoms and severity of SBS depend on the anatomic sections of the intestine that are resected, the length and absorptive capacity of the remnant bowel, and the presence of active primary disease . PatientOur patient had an ileocolic anastomosis (left colon in continuity), without ileocecal valve, with multiple intestinal resections and a remaining small bowel of about 110 cm. These are the patients who exhibit the greatest risk for development of dehydration and malnutrition. Ileal resection also reduces the plasma concentration of various digestive hormonal mediators such as GLP-1, GLP-2, and Peptide YY, all synthesized by enteroendocrine L cells in the distal ileum and colon .et al. [P = 0.030) significantly, crypt depth (P = 0.010), and mitotic index (P = 0.010). Afterwards, a first long-term (24-week) randomized placebo-controlled study (STEPS-1) of TED in 83 patients with SBS on parenteral support was published. Responders were patients who reduced by >20% in parenteral volumes from baseline at Weeks 20 and 24 (63% of patients) [TED, acting similarly to GLP-2, increases small intestinal mucosal growth by enhancing crypt cell growth and inhibiting apoptosis; also, it decreases gastric motility and reduces gastric secretion, increases mesenteric blood flow, and supports the gut barrier function in animal and human studies . The opeet al.  first evatients) , 10. DatAt the moment the literature does not report clinical studies or case reports evaluating the use of TED in patients affected by SBS on enteral nutrition due to the off-label indication. So far, this is the first case which demonstrated that this kind of treatment may allow a drastic reduction in daily evacuations, interruption of enteral nutrition, and improvement of quality of life to be obtained. Still under treatment, the patient did not developed serious side effects, confirming the long-term safety of the medication. Thus, TED could be a promising and effective therapy even in patients with SBS on enteral nutrition, and this case supports thinking ‘out of the box’ when clinical indication is present. By the way, further studies are mandatory to recommend the use of TED in patients not in parenteral nutrition as suggested by current guidelines.Performance of the research and writing of the manuscript: B.B. and E.S. Clinical management of the patient: All authors. All authors read and approved the final manuscript.The authors declare that they have no Conflict of interest.


Cardiovascular diseases (CVD) are the leading causes of morbidity and mortality worldwide. The complex etiology of CVD is known to be significantly affected by environmental and social factors. There is, however, a lag in our understanding of how population level components may be related to the onset and severity of CVD, and how some indicators of unsatisfied basic needs might be related to known risk factors. Here, we present a cross-sectional study aimed to analyze the association between cardiovascular risk factors (CVRF) and Social Development Index (SDI) in adult individuals within a metropolitan urban environment. The six components of SDI as well as socioeconomic, anthropometric, clinical, biochemical, and risk behavior parameters were explored within the study population. As a result, several CVRF  were found in a higher proportion in the low or very low levels of the SDI, and this pattern occurs more in women than in men. Canonical analysis indicates a correlation between other socioeconomic features and anthropometric, clinical, and biochemical factors . Further studies along these lines are needed to fully establish how to insert such associations into the design of health policy and interventions with a view to lessen the burden of cardiovascular diseases, particularly in metropolitan urban environments. Although much progress has been made in understanding the effect that the complex context of environmental, biological, social, and collective domains has on noncommunicable diseases (NCDs), cardiovascular diseases (CVD) are still the leading causes of death in human populations . Most ofRecently, Mexico is undergoing a transition in the burden of NCDs from groups with high socioeconomic status (SES) to those in low SES that have been systematically neglected . EconomyHuman Development Index (HDI)  , 15.United Nations Development Program (UNDP) in the 1990s to measure the development level inside the regions, but also, to help countries build specific development indices to identify more precisely the social inequalities within them (Sustainable Child Development Index (SCDI) be integrated into databases as The Social Hot-spots Database to measure and compare the level of development in different geographical areas, and between population groups  and socioeconomic development using the HDI, some studies have been advancing in relation to coronary heart disease (CHD). Zhu et al. investigated the patterns in Asia, Europe, and North America regions . Their rfair and equitable social development can only prosper if at the same time, the investment is made in education, health, and nutrition of human capital  might influence the people's capacity to be healthy or diseased, but also, supporting decision makers to develop policies in less favored regions , 27. Ama capital .Mexico is an upper-middle-income country, is the 13th-largest country in the world, with more than 126 million inhabitants. While Mexico has become a developed country, more than half of their inhabitants lives in a state of precariousness and lack of inclusion conditions and social differences are becoming more acute . For dec2 (Mexico City (CDMX) is the capital of Mexico and one of the 32 states of Federal Entities . CDMX is2 . CDMX is2 .Social Development Index (SDI) is based on the HDI, and is the instrument used to define, measure, and classify the degree of social development of territorial units. Social development in the Mexican context is a process of economic improvement and equalization of the general welfare conditions, since poverty constitutes the most serious expression of the limitations to improve the quality of life. In this sense, social development is a central objective of the action of the Government of Mexico City. The Political Constitution of the United Mexican States considers as rights for social development, education, health, nutritional, and quality food, housing, the enjoyment of a healthy environment, work, and social security  under number 13-802. All patients gave written informed consent. The enrollment started in September 2014 and is ongoing. A more detailed description of the study is presented in This cross-sectional analysis includes the complete data from the baseline visit of 2,084 healthy adults residents of Mexico City, between 20 and 50 years old of 0 cohort . This isThe participants are being evaluated every 2 years over a period of 10 years or until they develop systemic hypertension (primary outcome). At every visit, the blood pressure, laboratory tests, anthropometric measurements, sociodemographic data, and cardiovascular risk factors are assessed by trained personnel by means of standardized instruments, methods, and structured questionnaire.Through a personal interview, with a structured questionnaire, the following sociodemographic information is being obtained: marital status , educational level concluded , and occupational class .JNC 7 standard procedure; hypertension status (HTN) was defined as a systolic blood pressure ≥ 140 mm Hg and/or a diastolic blood pressure ≥ 90 mm Hg , Coulter LH Series Pak Reagent Kit. The reference values are as follows: fasting plasma glucose (70–105 mg/dl), triglycerides (40–200 mg/dl), low-density lipoprotein cholesterol (LDL-C) (80–130 mg/dl), high-density lipoprotein cholesterol (HDL-C) (women: >50 mg/dl and men: >40 mg/dl), total cholesterol (140–200 mg/dl), uric acid (women: 3.80–6.20 mg/dl and men: 4.80–8.00 mg/dl), serum creatinine (women: 0.60–1.00 mg/dl and men: 0.70–1.30 mg/dl), Atherogenic Index , and serum sodium (136.00–145.00 mmol/l) . Urinary sodium and potassium are determined by the ion selective electrode method, and urinary creatinine is determined by Jaffe's colorimetric assay using an automated analyzer. A urine sample is considered complete when urine creatinine levels are within the standard excretion rate . The refInternational Physical Activity Questionnaire [IPAQ]: categorized into low, moderate, or high physical activity levels;  to better  . Accordiic needs . Basic nic needs  , which refers to the material of the floor, ventilation, and lighting condition, the number of rooms in the house, and the number of people (occupants) living in it.Educational access refers to people 15 years of age or older who reached the basic education level, which in Mexico is high school studies.Access to social security (ASS) refers to the right of the household members to any of the Mexican health systems: Mexican Institute of Social Security , Civil Service Social Security and Services Institute , Mexican Petroleum , Mexican Defense, Mexican Navy, Institute of Health for Well-being , or private institutions.Durable goods refers to material goods whose value is equal to or greater than (17.81 USD) and/or the possession of at least three material goods .Sanitary adequacy is constructed from three sub-components: about the source of water supply, the existence of toilet and access to the drainage system.Electricity access is the dichotomous indicator, whether or not it lacks energy adequacy.W' > 0.05); numerical data are presented as median and inter-quartile range , and qualitative variables as absolute values and percentages .Analyses were performed using [R] version 4.0.2 . The disp <0.20), a one way nonparametric test was used to compare the SDI categories within each sex.The levels of the SDI  were compared against the CVRF and also against sexes; therefore, a two-way ANOVA was used for numerical variables. When the interaction term was statistically significant (2 at 95% significance) or Cramer's V coefficient  were used when the expected values were equal or <5  as well as the linear interrelation between them, canonical correlation was used for the multivariate analysis .r lineal combinations within the first set of variables as follows:The main objective of this type of analysis is to identify the and within the second set of variablesThe most significant correlation coefficient will be shown between U1 (see Equations 1 and 2) and V1, the second between U2 and V2, and so on. There should be no correlation between U1 and U2 and U3, and neither between V1 and V2 and V3, these combinations are the so-called canonical variables.For this study, the one set of variables (U) was as follows: DSI, sex, marital status, educational level, and occupational class, and the following set of variables (V) was as follows: biochemical parameters , systolic blood pressure, waist-to-height-ratio (WHtR), and alcohol consumption.dfnum = predictors−1 = 69. Since we have a sample size of 2,084 individuals, the number of degrees of freedom for the denominator dfnum = samples−predictors = 2014. With these in mind, we obtained a statistical power larger than 99.999% under a significance level of 1E−07, even for very mild effect sizes f2 = 0.1.Statistical power was calculated by F-statistics. For the full study, we have 71 variables so that the maximum possible number of predictors is 70. Hence, the number of degrees of freedom for the numerator quality and available space in the home and access to social security, 55 and 95%, respectively, were classified as very low, while more than 90% of participants were classified as medium or high regarding educational access, durable goods, and sanitary adequacy. The entire population studied had access to electricity.Data were collected from 2,084 healthy adult residents of Mexico City, 1,314 (63%) women and 770 (37%) men. Marital Status most participants were married (46%); however, no significant differences were identified in relation to the SDI's levels by sex. Education level also showed an interesting distribution among the SDI's levels within each sex. Most women and men, regardless of the SDI level, had an educational level of high school or college; however, it is still perceived that women compared to their male counterparts at lower levels of development have less access to basic education  tend to decrease as the SDI level increases  showing that women in disadvantaged social classes were more likely to develop overweight or even obese and accumulate abdominal fat than those in higher SDI's levels ; and in men, in the high level: 109 mm Hg, in the medium: 111 mm Hg, in the low: 111 mm Hg, and in the very low: 113 mm Hg (p < 0.05). However, since this study aims to identify the incidence of hypertension all blood pressure levels (systolic and diastolic) are within normal values—below 120/80 mm Hg (see Regarding of m Hg see .height. Women and men in higher SDI's levels had larger size than those in lower SDI's levels (see p < 0.001), and men in high: 171 cm and in very low: 169 cm (p < 0.05).A similar situation, however, in the opposite direction happened to the vels see ; women iserum and urinary biochemical tests among SDI's levels by sex are shown in glucose median values, it seems that women in the high SDI level had lower values than those in the other three levels . In relation with HDL-C, an increment of the median values was observed as SDI level increased; in very low: 48 mg/dl, in low: 50 mg/dl, in medium: 51 mg/dl, and in high: 53 mg/dl (p < 0.001). In the case of triglycerides, the opposite pattern was observed; serum median values were lower in higher SDI's levels  (see Distribution of 001) see .glucose values among SDI's levels without a specific pattern ; while potassium showed a different pattern, larger median values were observed in higher SDI's levels than in lower levels , this pattern was also identified in women . Furthermore, worth mentioning that sodium levels between sexes were significantly different: men had larger median values than women , however the significance did not hold after Bonferroni's correction, p < 0.05 . In the case of men, the proportion of those with this habit in the high level of the SDI was significantly larger than those without it (27 vs. 17%), whereas in the very low level of the SDI the proportion of men without the habit was larger than those with the habit .The distribution of ress see , 7. In rphysical activity and psychological stress, the highest proportion of women and men with a moderate degree of both parameters were mainly concentrated in the low, medium, and high SDI's levels. There was no statistical difference between the groups compared .–63.qualiRegarding anthropometric and clinical parameters, we identified that women had larger values of waist circumference, WHtR, and BMI in lower levels of the SDI. SBP also was significantly higher in lower SDI's levels in men and in women as well. In relation to biochemical tests, an association with SDI's levels in women was observed. Larger values serum glucose and triglycerides, and lower values of HDL-C were related to lower levels of SDI. In the case of urine tests, this same pattern was found in relation to sodium levels in men, whereas for potassium, both sexes exhibit an inverse pattern.Several studies have identified associations between CVRF and SES. People in socioeconomic disadvantage have a higher likelihood of presenting CVRF, than those in socioeconomic wellness. In a review by Zhu et al., unhealthy nutrition patterns were more frequent in lower SES . This SELindavista Study, a project for multiple intervention trial on cardiovascular risk factors   , where 7ur study .Additionally, we found that a lower level of SDI, lower educational levels, being unemployed, and single were associated with increased serum glucose, LDL-C, triglycerides, urinary creatinine, systolic blood pressure and WHtR, as well as, a decreased serum levels of uric acid, creatinine, urinary potassium, and lower alcohol consumption. Aside from these broad context issues, our analysis was also able to unveil the associations between particular cardiometabolic factors and the socioeconomic development, approximated by SDI but also by educational level and occupational class. This interaction is indeed a nascent research area in public health that is starting to gain attention recently see  70–72).–72.70–72Overweight and obesity were also found to be positively correlated with human development index and urban environments in India  as well Likewise, another review study, by Mendoza-Herrera et al. , on the In summary, in this study, we demonstrated that Mexican urban population accumulates several important risk factors related to metabolic abnormalities . A large percentage of the population studied in lower levels of development is deprived of access to health care facilities. The problem seem to be more complex for women, in whom low levels of access to formal employment and in consequence limited access to social protection persist. Also the analysis shows how particular SDI components  deficits could reduce the capacity to change that panorama see .Mexico and nations with a similar or lower HDI experience greater challenges related to CVRF . In thesThis study explores the relationship between SDI, as a social determinant of health proxy, and cardiovascular risk within an upper middle income country to analyze how these social inequities in health might be implicated in the development of biological conditions such as the increment in the body mass or in the levels of blood sugar, triglycerides, LDL-C, etc. As a result, some disparities regarding cardiovascular risk factors were observed in lower vs. higher SDI, particularly in women. These findings could facilitate cardiovascular risk factors control planning in countries experiencing both socioeconomic and epidemiological change related to social-economical disparities such as Mexico. This study also has some limitations. Since recruitment was made through massive disseminating methods, participation was voluntary, and women tended to care more for their health and participate more than men, resulting in a slightly biased toward female participants. Another limitation is that we used the SDI data, which are published by the Government of Mexico City and therefore we have to rely on the quality of data compiled by that secondary source.The present study shows how SDI and other human development components impact directly and indirectly the CVRF through intermediate issues related to some metabolic aspects, lipids in particular and healthy weight. Concerning sex, in our study population the proportion of young men under 50 reported more traditional risk factors than women in similar age brackets, but when we explored the phenomena by strata of the SDI, the situation seems to turn less favored toward women with low levels of development.Quality and available space in the home and Health care access as elements of general concern for public health interventions and nutritional conditions, which may help reduce health inequalities in the Mexican population, in particular in large metropolitan areas such as Mexico City. So, we presented SDI as a feasible and a complementary instrument to collect information about socioeconomic strata, Mexican neighborhoods, and their relation to cardiovascular health at the population level with public health policy design in mind.We found SDI, but also two of its components: We hope that this study will help to conduct future research using a socially oriented perspective in order to implement primary prevention and health promotion strategies in scheme of cardiovascular risk factors and to continue monitoring it in future studies. As discussed previously, the careful analysis of population level association of human development components and risk factors for cardiovascular disease may provide health policy makers and urban setting decision makers with solid tools for scientifically guided intervention designs.The original contributions generated for the study are included in the article/This study was approved by the Research and Ethics Committees at INC-ICh with number 13-802.MM-G, GG-E, MV, and EH-L have been involved in conceptualization, methodology, formal analysis, and data interpretation. GG-E, JR-G, DM-P, CM-R, and MV have been involved in data collection, data curation, and management. MM-G, GG-E, MV, and EH-L have been involved in the preparation of the manuscript. EH-L and MV have been involved in funding acquisition. 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.


To analyze the development of cardio-oncology, summarize the research achievements, and provide proposals for its future research.  The web of science database was used to search for “cardio-oncology” and “oncocardiology” related articles from the beginning of the database (1970) to April 5, 2019. Excel 2016 and Cytoscape were used to analyze the trend of cardio-oncology research. n = 107). Researchers paid more attention to the prevention and treatment of cardiotoxicity (n = 54). Experimental researches were a small part of all studies (n = 72), mainly focusing on the study of cancer drugs' cardiac injury, test indicators of cardiotoxicity, and preventive drugs. The United States (n = 156.25), Italy (n = 48.5), and Canada (n = 23.5) published the most articles, making a great contribution to the development of cardio-oncology.  A total of 356 articles were obtained. The number of articles has grown rapidly in recent years. Cardiac injury caused by tumor therapy was a research hotspot ( Cardio-oncology has been developing rapidly and receiving a large amount of research efforts in recent years. Most articles on cardio-oncology were published by the authors from the United States (44%) and Italy (17%), while other countries need to pay more attention to cardio-oncology. As an independent discipline, cardio-oncology is certainly in need of significant progress, but it has formed a basic framework, which has obtained many leading theories and meaningful achievements in diagnostic criteria, diagnostic methods, prevention and treatment, mechanism research, and influencing factor. Cardiac injury of tumor drugs has always been a research hotspot in this discipline, and there is still a lot of research space. The research about detection methods of cardiotoxicity and preventive drugs is gradually increasing. Basic research lags behind, and many mechanisms are still unclear. Cancer and cardiovascular diseases are the main causes of morbidity and mortality in modern society . Cancer Bibliometric analysis is an approach to evaluate the academic impact and characteristics of publications in a specific research field over time . It has In this study, we aimed to provide detailed evaluation of the status of cardio-oncology by using bibliometric analysis, so that more researchers can realize the importance of this field and solve problems that hinder development. At the same time, through the summary of research methods and contents, our study reflected the current situation of the research and provided suggestions for further studies. We hoped to get insights into cardio-oncology which have been gained over the past years by analyzing the publication year, journal, authorship, country and interactions, article type, research content, H-index, citation density, funding source, etc.Web of science database has the advantages of high quality, fast update, and little data error . The webn = 5), unpublished Meeting Abstract (n = 49), errata description (n = 1), and literature not available (n = 1) and finally obtained 356 articles all related to cardio-oncology. These articles were all from the SCI/SCIE database and have the same weight.The article of each search result was read thoroughly to ensure that cardio-oncology was the major subject of the research. We excluded literature unrelated to the subject study  publication information, including authors, journal, publication year, and author's country; (2) article content, including article type, research content, and funding source; and (3) bibliometric content such as impact factor, citation density, and H-index.n = 343), Spanish (n = 4), Portuguese (n = 4), Hungarian (n = 1), German (n = 1), and French (n = 3). The earliest articles in the web of science were published in 2010 (n = 4), followed by an exponential increase in the number of documents. In 2018, 97 articles were published and this proportion was as high as 27.2%. Among the 356 articles obtained, there are 6 language types, including English (n = 240) was “2016 ESC Position Paper on Cancer Treatments and Cardiovascular Toxicity Developed under the Auspices of the ESC Committee for Practice Guidelines.” This article discussed nine main categories into which the cardiovascular complications of cancer therapy can be divided. We refer to the number of times that each document is cited every year as the citation density. For the articles which were published in 2018 and beforehand, the citation density ranged from 0 to 80 times, and the average citation density was 4.015 times. There are three articles that have a citation density more than 30 times including two guidelines and one retrospective study and 292 articles (82%) less than 5 times. Similarly, through web of science, we obtained the H-index of the article and analyzed it, excluding 7 articles that could not obtain the H-index. The results showed that the H-index ranged from 0 to 35. The number of articles with H-index of 0 was 136 which occupied the largest proportion (38.2%), and 21 articles with an H-index more than 10 accounted for 5.9% of all publications. The article of the highest H-index (n = 35) was “Cardiovascular Side Effects of Cancer Therapies a Position Statement from the Heart Failure Association of the European Society of Cardiology” published in 2011.The number of citations related to cardio-oncology varied from 0 to 240 times, with an average of 10.455 times per article. 275 articles were cited less than 10 times (77.25%), and only 14 articles were cited more than 50 times (3.93%). The article which had the maximum citation . n = 107), followed by prophylaxis and treatment (n = 54) and detection method (n = 51). The articles on cardio-oncology were classified according to the study content, including cardiotoxicity, prevention and treatment, detection method, subject to discuss, mechanism, research progress, consent consensus, influence factor, and practice situation. Among them, cardiotoxicity had the largest number , followed by Italy (n = 59.5), Canada (n = 23.5), Germany (n = 16), and Japan (n = 14). The top 10 countries were ranked , followed by University Hospital Essen (n = 6) in Germany, The University of Texas (n = 5) in the United States, Aix-Marseille University (n = 4) in France, Mayo Clinic (n = 4) in the United States, and Shizuoka Cancer Center (n = 4) in Japan. In the articles on cardio-oncology, a total of 67 authors published more than one article as the first author or correspondent author. There were 8 authors who published more than 4 articles, and, among them, Salvatore Patanè from Italy was the most productive author (n = 13). Cardiologia Ospedale San Vincenzo in Italy was the most prolific research institute in cardio-oncology  recorded not receiving any funding. Only 127 articles (35.7%) were funded by 229 funding agencies. The United States provided the most funding and had the most funding agencies. n = 8), followed by USA-UK (n = 7), UK-Netherlands (n = 6), and UK-Switzerland (n = 5). According to analysis of national cooperation, the cooperation between the USA and Canada was the most frequent , and the average citation density was 4.015 times. There were 21 articles with an H-index that is greater than 10, while the H-index in 136 articles (38.20%) is 0. We speculate that the number of studies in this discipline is relatively small or there are more new researches, resulting in low level in the number of citations. 12 of 21 articles with H-index >10 were cited more than 50 times, and, among them, three articles were consensus guidelines, which summarized the current research results of cardio-oncology in detail and introduced the cardiovascular diseases caused by radiotherapy, chemotherapy, and targeted treatment. These three articles also provided suggestions for the prevention and treatment of cardiovascular diseases. In addition, there were also two articles about the drugs with cardiotoxicity, two articles reviewing the prevention and treatment of cardiotoxicity, two articles discussing the mechanism of cardiotoxicity, two articles describing the experiment of cardiotoxicity leading to the change of cardiac biomarkers, and one article about the treatment of tumor combined with atrial fibrillation. In conclusion, researchers were more concerned about the cardiotoxicity of cancer drugs and how to prevent cardiac damage.Most of the articles on cardio-oncology were cited less than 10 times (72 articles (20.22%) were experimental research; among them, 29 articles (40.28%) were prospective studies. The percentage was small, but, in recent years, the experimental research was growing rapidly, and the proportion in 2018 reached 30.21%. It can be seen that although experimental researches were relatively few, they have gained attention by scholars in recent years. These experimental studies can be divided into 6 categories according to the content. Firstly, 25 articles studied the cardiovascular injury caused by tumor treatment via different experiment methods. Secondly, 17 articles explored the indicators of early detection and monitoring of cardiotoxicity, including biomarkers and imaging examination. Thirdly, 9 articles discussed the drugs to prevent cardiotoxicity. In addition, 8 articles studied the mechanism of cardiotoxicity. Moreover, 6 articles investigated the development of cardio-oncology in different regions. Furthermore, 5 articles reported the interaction between tumor and cardiovascular disease. Unfortunately, there was no research result about radiotherapy. Another feature of all publication was that the proportion of review article is 48.31%. These review articles described cardiovascular damage and recent research progress in chemoradiotherapy. Cardio-oncology serves as a bridge between heart disease and oncology [β-blocker such as perindopril, valsartan, metoprolol, and bisoprolol. These medicines are expected to be widely used in future clinical practice. Besides, 12.92% of the articles discussed the importance of the subject, the direction of development, and how to develop the subject, affirming the importance of cardio-oncology. It is worth noting that, in others, we can see some experts who have studied the relationship between cardiovascular disease and tumor disease. The research content of cardio-oncology is not limited to the toxicity of radiotherapy and chemotherapy to the heart. The study of disease similarities in two disciplines contributes to the development of cardio-oncology.In terms of research content, these studies included prevention and treatment, detection method, mechanism, and influence factor, which constitute the skeleton of the discipline. 30.06% of articles were about cardiotoxicity in tumor treatment, reflecting the research direction of the discipline. We could find that the previous research focused on three aspects. First of all, cancer drugs that are prone to cardiac damage were the core of the research. In the early stage, anthracyclines were mainly studied. Recently, the research about monoclonal antibodies and targeted drugs is gradually increasing. Furthermore, main research drug of cytotoxic drugs was cyclophosphamide. Other sorts of drugs, such as hormones, were less studied. Secondly, at present, monitoring the indicator of early cardiotoxicity is a hotspot. Early detection of cardiac impairment is an important step in adjusting tumor medication and giving prevention and treatment of angiocardiopathy. It not only confirmed the role of traditional indicators such as LVEF and cardiac troponin, but also found indicators such as global longitudinal strain (GLS) and myeloperoxidase (MPO) that respond to early cardiac damage. Finally, drugs to prevent cardiotoxicity will be the focus of future research. Currently, preventive effects of drugs have been proved, and they are generated by Angiotensin-Converting Enzyme Inhibitor (ACEI), Angiotensin Receptor Blocker (ARB), and The articles on cardio-oncology were published in 148 journals, including cardiovascular disease journals, oncology journals, and comprehensive magazine. 62.16% of journals published only one literature, and 16 journals published more than five cardio-oncology articles.In the articles on cardio-oncology, the authors from United States contributed 44%, far exceeding other countries, followed by Italy with 17%, Canada with 7%, and Germany with 5%. The United States leads the world in the field of cardio-oncology research, which is consistent with its leading position in many other fields. However, it is regrettable that there are still many countries with insufficient knowledge of this subject and few research results.A total of 31 countries had cooperated with other countries and formed 138 kinds of cooperation between two countries. There are 70 types of cooperation that happened once, accounting for 51.06%, and 42 kinds of cooperation (30.66%) happened twice. In all countries, the United States had more cooperation than anyone else, and the frequency of cooperation between USA and Canada is the highest which is 8 times in total. European countries such as Italy, Britain, Canada, and The Netherlands had also cooperated many times, while cooperation among nations in Asia, Africa, and South America rarely appeared. International cooperation articles are often more significant than other articles . Many maSalvatore Patanè from Italy had the largest number of published articles, and his organization, Cardiologia Ospedale San Vincenzo, was the institution with the highest amount of literature. Corresponding to the national contribution, the authors who published more than 4 articles are American or Italian. The NIH, NHLBI, and NCI in the United States funded 49 studies; hence the United States had the maximum number of funding this research. Cardio-oncology has not been funded by large pharmaceutical companies, which may be related to its research content. Pharmaceutical companies may not be willing to provide additional expenditures for the study of drug side effects. Therefore, the development of cardio-oncology needs more help from government.As the USA provided the most funding, this reflects the strong interest of US authors and funding agencies in the discipline, and, in the future, this may continue to contribute to the development of cardio-oncology and have a positive international impact.Cardio-oncology has entered a period of rapid development. Some countries have launched related services, but that cannot meet the needs. As early as 1975, there were reports of cardiotoxicity of Daunomycin and Adriamycin , 21. HowReviewing the recent research results, the cardiotoxicity of conventional drugs such as Anthracyclines, cyclophosphamide, and Trastuzumab has been clearly recognized. In recent years, the rapid development of emerging therapies, such as immunotherapy and targeted therapy, has played an increasingly important role in anticancer therapy. The cardiotoxicity brought by these therapies has also aroused attention, and new research results in these fields are being published , 28. TheWith regard to cardiac dysfunction caused by tumor treatment, research on heart failure is relatively perfect. There is a basic consensus in terms of toxic drugs, detection methods, diagnosis methods, and prevention and treatment schemes. However, focusing too much on heart failure led to the lack of study, which investigated other kinds of cardiovascular diseases. Research studies about arrhythmia or myocardial damage caused by tumor treatment were far less rich than the study of heart failure. Indeed, heart failure is the main manifestation of cardiovascular injury and hotspot of research, but we should strengthen our understanding of cardiovascular disease other than heart failure, especially to make up for the deficiency of research on detection methods and preventive drugs.We still face many challenges in the future. As new chemotherapeutic drugs continue to be produced, reasonable cardiotoxicity assessments and prevention programs for various chemotherapy regimens require more funding. We need to further standardize cardiotoxicity detection methods. We also need to clarify the time when to start the prevention of cardiotoxicity to have the greatest benefits and to fill gaps in the study of multiple chronic conditions. We hope that researchers will recognize that multidisciplinary cooperation is a necessary condition for the development of cardio-oncology , 30, 31.Our research had certain limitations. The content we searched for was only the web of science. It did not include other databases such as PubMed, paper publications, and video materials. Our search terms were “cardio-oncology” and “oncocardiology,” so it was unavoidable that some articles might be missed. We had not included these relevant contents into the research, and there was a certain deviation. There may be many factors that affect the citation numbers of an article, and the citations cannot fully reflect the academic impact of an article. The United States had the largest number of articles, but the article that had been cited most highly was from Europe, and the author who published the most articles was Italian. Although we analyzed cardio-oncology as comprehensively as possible, it was still difficult to avoid bias. The density of citations is greatly influenced by the development of the discipline. The earlier the article is published, the more the times it is cited, and the new research results published in recent years are less frequently cited. Although the H-index compensates for the deficiency to a certain extent, it is still difficult to perfectly capture the impact of new research results. Despite this, we have analyzed the development and research contents of cardio-oncology as comprehensively as possible, with a view of summarizing this subject and providing a certain directive role in the period of rapid development of cardio-oncology.In this study, we used bibliometric methods to analyze the articles on cardio-oncology and summarized the research progress of this discipline. The establishment and development of a discipline require core research (cardiotoxicity), diagnostic criteria, diagnostic methods, prevention and treatment, mechanism research, influencing factors, and disciplinary development planning. The study of cardio-oncology has these conditions but needs improvement. Researchers mainly focus on cardiovascular damage of tumor drugs. It would still be a hotspot in the future, because there are still many drug toxicities that have not been investigated. With the continuous report of cardiotoxicity of tumor drugs, how to monitor cardiotoxicity and prevent heart damage will be a new hotspot. Previous studies focused on heart failure, while there was insufficient research on other cardiovascular diseases. Unfortunately, many problems were found in the clinic rather than basic research. Hence, basic research failed to provide beneficial support for clinical research. It is because many problems were found in the clinic rather than basic research that basic research failed to provide beneficial support for clinical research. We hope that as the research results continue to be enriched, a system would be established to guide the use of cardiotoxic drugs, cardiotoxic monitoring, and the timing of initiation of cardiovascular disease prevention.


Heterogeneity was assessed while using Q statistics. The ANOVA-Q test was used to value the differences among groups. Publication bias was analyzed and represented by a funnel plot. Curcumin treatment does not show a statistically significant reduction between treated and untreated patients. On the other hand, glycosylated hemoglobin, homeostasis model assessment (HOMA), and low-density lipoprotein (LDL) showed a statistically significant reduction in subjects that were treated with curcumin, respectively . When considering HBA1c, the meta-regressions only showed statistical significance for gender (p = 0.034). Our meta-analysis seems to confirm the benefits on glucose metabolism, with results that appear to be more solid than those of lipid metabolism. However, further studies are needed in order to test the efficacy and safety of curcumin in uncomplicated type 2 diabetes.Diabetes mellitus is an important issue for public health, and it is growing in the world. In recent years, there has been a growing research interest on efficacy evidence of the curcumin use in the regulation of glycemia and lipidaemia. The molecular structure of curcumins allows to intercept reactive oxygen species (ROI) that are particularly harmful in chronic inflammation and tumorigenesis models. The aim of our study performed a systematic review and meta-analysis to evaluate the effect of curcumin on glycemic and lipid profile in subjects with uncomplicated type 2 diabetes. The papers included in the meta-analysis were sought in the MEDLINE, EMBASE, Scopus, Clinicaltrials.gov, Web of Science, and Cochrane Library databases as of October 2020. The sizes were pooled across studies in order to obtain an overall effect size. A random effects model was used to account for different sources of variation among studies. Cohen’s  Type 2 diabetes (T2DM) is an important issue for public health, and it is growing in the world; in fact, according to the World Health Organization (WHO) report in 2016, 422-million people are diagnosed with diabetes .Lifestyle risk factors that are related to diabetes, as obesity and overweight are two major risk factors. The treatment of T2DM includes the use of anti-diabetic drugs and prevention based on lifestyle habits. In recent years, there has been growing research interest on the efficacy evidence of curcumin use in the regulation of glycemia and lipidaemia .Curcumin is the main bioactive component that is extracted from the rhizome of Curcuma Longa. It is a product used since ancient times, in cuisine, as in traditional medicine . The proIts molecular structure makes it possible to intercept reactive oxygen species (ROI) that are particularly harmful in chronic inflammation and tumorigenesis models .Curcumin can have a therapeutic effect on some chronic diseases, such as rheumatoid arthritis, coronary artery disease, atherosclerosis, T2DM, and obesity .Ramirez-Bosca et al. showed that daily treatment with curcumin can decrease the low-density lipoprotein (LDL) in healthy subjects . In addiIn order to evaluate its effectiveness, some studies have been conducted on the effects of curcumin on glycemic and lipid control in subjects with uncomplicated T2DM ,14,15,16In this systematic review and meta-analysis, we aim to evaluate the effect of curcumin on glycemic and lipid profile in subjects with uncomplicated T2DM.The papers that were included in the meta-analysis were sought in the MEDLINE, EMBASE, Scopus, Clinicaltrials.gov, Web of Science, and Cochrane Library databases as of October 2020. The search terms used were: curcuma or curcumins or turmeric AND type 2 diabetes or diabetes;  AND (“Curcuma” [Mesh]) and applied the following filters: humans, published articles from 2000 to 2020, and clinical trials.The papers were selected while using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart  and the p-value, was used as a measure of effect size [2, Tau, and Tau2. The stability of study findings was checked with moderator analysis. A subgroups analysis was also performed while considering the country of primary studies, because four of seven studies were conducted in Iran. The ANOVA-Q test was used to value the differences among groups. Publication bias was analyzed and represented by a funnel plot; funnel plot symmetry was assessed with Egger’s test [The sizes were pooled across studies in order to obtain an overall effect size. A random effects model was used to account for the different sources of variation among studies . Cohen’sect size . Heterogr’s test . Finallyr’s test . Finallyr’s test .The literature search highlighted the presence of 529 references . After rBMI was investigated in three studies ,12,13 inp = 0.008, with moderate heterogeneity (I2 = 42.42), but not statistically significant (p = 0.107). Publication bias analysis did not highlight any differences between the observed and estimated values. It should be emphasized that there is a difference between the studies conducted in Iran and those conducted in other countries (p = 0.443). The meta-regressions only showed statistical significance for gender (p = 0.034).Glycosylated hemoglobin was evaluated in five studies ,13,15,16ountries ; howeverp < 0.001,   .p = 0.021, I2 0.00 , −0.57 , with 1 trimmed study. The subgroup analysis revealed a non-statistically significant difference.Triglycerides were evaluated in five primary studies, involving a total of 476 patients ,14,15,16p < 0.001, −0.40  (p < 0.001) with two trimmed studies. No statistically significant associations were found in meta-regressions , for the prevention, cure, and treatment of cardiovascular and metabolic diseases ,25,26. SThe results of our meta-analysis seem to confirm this modulating capacity on lipid metabolism. The trials considered highlighted an overall reduction in LDL, TG, and TC in patients with uncomplicated T2DM. This result does not seem to be affected by statistical heterogeneity. There is a moderate publication bias. The low fail-safe for LDL, HDL, and TC indicates caution in the interpretation of the overall result, even if a high Rosenthal value allows for the observation found to be considered valid . In ordeBecause hypoglycemic properties of curcumin have been known since 1972 ,37, the Hb1Ac and HOMA show significant results without statistical heterogeneity and publication bias. Regarding Hb1Ac, the subgroup analysis shows a difference between the studies that were conducted in Iran and those conducted outside Iran; on the contrary, this is not the case for HOMA, which shows concordant results. The hypoglycemic capacity of curcumin has also been tested in prediabetic populations with some success .Concerning Hb1Ac and HDL, the results of the meta-regressions only show statistical significance with respect to gender.Our meta-analysis seems to confirm the benefits on glucose metabolism, with results that appear to be more solid than those of lipid metabolism. In conclusion, the daily supplement of curcumin could improve some metabolic aspects of uncomplicated T2DM patients.However, further studies are needed in order to test the efficacy and safety of curcumin in uncomplicated T2DM. The limitations of the present work can be attributed to some biases present in the primary studies: the small numbers of enrolled patients and the possible impact of grey literature. These aspects cannot be totally corrected through the meta-analytic technique.


Delay phenomenon can be used for better blood supply of the flap in plastic surgery. Effects of Montelukast have been observed to reduce ischemia/reperfusion injury in various organs due to angiogenic and anti-oxidant effects. The present study aimed to determine the role of Montelukast as medical delay of the flaps.th days, the photos were taken and the size of the necrotic area of the flap was measured. In this experimental study, 42 Wistar rats were divided into 3 equal groups. These groups were Surgical Delay Group (SDG), Medical Delay Group (MDG) and Control Group (CG). In SDG, 8×3 cm rectangular randomized random skin flap was first surgically delayed at rats’ back. The MDG received 10 mg/kg oral Montelukast via orogastric tube for 5 days as medical delay. In MDG and SDG flap, harvesting was undertaken after a delayed period, but there was not any delayed period in CG. After delayed period, a segment of the skin flap was biopsied for assessing angiogenesis. After 14p=0.002). The same performance was reported between MDG and SDG, which were alike regarding survival and angiogenesis (p>0.05); while there was a significant difference between the control and surgical groups, as well as control and medical groups (p<0.05). Finally, the inflammation showed no significant difference (p>0.05).A significant difference was observed between the mean survival and angiogenesis (Regarding positive effects of Montelukast on survival and angiogenesis, it is recommended to be used as a medication for larger studies. However, blood conservation is considered as an important limitation, especially in random flaps. Each flap lost leads to an increased rate of operations, donor and receiver site deformity, limb loss risk, hospital stay, work withdrawal time, and disability.2Flap utilization has attracted a lot of attention in plastic surgery. Flaps are regarded as a complex of tissues with vascular supply. Random cutaneous flap is a skin flap harvested on the base of subdermal vascular plexus without innominated vessels. Lack of innominated vessels in random flaps leads to a higher necrosis rate than other flaps.th century. Delay can result in circulating the flap better and increasing the survival by implementing surgical and medical methods. However, the efficacy of surgical method has been confirmed although the use of medical method is controversial. Two techniques are available for surgical method including standard which is done with or without pedicle preservation and strategic, which is performed with ligation of minor pedicles and transition after two weeks.3Surgical delay phenomenon which was first introduced in 1921 may be used for better blood supply. This phenomenon was used for flaps during 163The related mechanisms for surgical delay effect include an increase in flap tolerance to ischemia, the reconstruction of vascular tissue and an increase in flap blood supply, a decrease in arteriovenous shunt, vasoconstriction, and prothrombotic substance, and accordingly an increase in vascular extension of flap via choke arteries of flap and stimulation of angiogenesis by VEGF and FGF. Regarding the disadvantages of this method, we can refer to an increase in surgical stages, possible incorrect incision of flap pedicle, and scar formation leading to disordered flap rotation. Accordingly, medical method may be theoretically regarded as the optimal alternative.4 Anti-coagulants, thrombolytics, and anti-spasmodics could play a significant role in some free flaps although no efficacy was found in other flaps in some other studies.5Some methods are implemented for medical delay development including, anti-inflammatory agents such as leukocyte aggregation and adhesion inhibitors, angiogenetic agents such as VEGF, PDGF, FGF, anti-spasmodic agents such as alpha-adrenergic antagonists, catecholamine release inhibitors, beta-agonist, direct vasodilators, and calcium channel inhibitors.5 However, no study, to the best of our knowledge, has evaluated this role in medical delay. Therefore, this study was undertaken to evaluate the Montelukast for medical delay in flap surgery.Angiogenetic agents are useful for medical delay although they are not regarded as accessible medications and include high costs. Montelukast as a leukotriene inhibitor is used for treating asthma and allergy. Montelukast inhibits leukotrienes, which act as angiogenesis inhibitors. Further, the related effects of Montelukast reducing ischemia/reperfusion injury in various organs have been reported in some other studies, which is related to angiogenetic properties and anti-oxidant effects.ketamine (20 mg/kg) and xylotene (2 mg/kg). Before each surgery, the single intramuscular dose of ceftriaxone (50 mg/kg) was administrated, which was repeated as single daily dose for 7 days after all surgeries and each rat’s back hair was shaved by an electrical shaver. After that, the skin was scrubbed by povidone-iodine solution. In this experimental study, 42 Wistar rats weighing from 350 to 450 gram were randomly divided into three equal groups. These groups were Surgical Delay Group (SDG), Medical Delay Group (MDG) and Control Group (CG). All surgical procedures in these groups were conducted under general anesthesia with intramuscular administration of 6 Regarding surgical group at the first stage, the flap was designed at the back of the rats. The skin was incised in all borders of flap except its base. In addition, the distal third of the flap was elevated from the fascia and the incisions of full-thickness skin was done till fascia. The flap was designed as an 8×3 cm rectangular, cephalic-based random skin flap at the back of rat. During the study, the animals were kept in a field with enough light and time of darkness. The temperature was preserved to optimal and their food was prepared. Each rat was kept in a separate cage and was cleaned regularly as described before.At the end of this stage, hemostasis was conducted by a bipolar electrocautery and accordingly the skin flap was returned to its original site and sutured to the surrounding skin by 4/0 Nylon . During After 14 days of the second stage operation, all rats of the SDG underwent general anesthesia. Furthermore, the photos of all flaps was taken by Nikon camera from 90 cm distance and a 3×3 mm biopsy was done from the most proximal part of the necrotic part of the flap for confirming necrosis . RegardiThe randomized skin flap was elevated from the fascia. Further, a 3×3 mm segment of the most distal part of the flap biopsy was obtained for assessing angiogenesis. After careful hemostasis, the flap was returned to its original site and sutured to the surrounding skin by 4/0 nylon stitches. Then, all rats of the medical group underwent general anesthesia after 14 days of the first stage operation. Accordingly, the photos of all flaps were taken by Nikon camera from 90 cm distance and a 3×3 mm incisional biopsy was done from the most proximal part of the necrotic part of the flap. This biopsy was used to confirm necrosis microscopically.In the control group, all rats underwent general anesthesia without any delay procedure. The randomized skin flap was elevated from the fascia and a 3×3 mm segment of the most distal part of the flap was obtained for biopsy to assess angiogenesis. After careful hemostasis, the flap was returned to its original site and sutured to the surrounding skin by 4/0 nylon stitches . After 17 In order to analyze the related data, Mann-Whitney, Kruskal-Wallis, Chi-Square, and Exact-Fisher tests were used and the significance level was reported to be 0.05.Then samples for assessing angiogenesis were stained with H&E and CD31 staining. The angiogenesis was assessed by measuring new vessels under power field of 40 and samples for confirming necrosis were stained with H&E staining and necrosis was evaluated. The success rate of flaps was determined with flap photography, as well as measuring the remaining live flap surface with Image-J instrument. Based on the vessels per HPF, the angiogenesis was divided into mild (<5), moderate (6-10), and severe (>10) group in high power filed.p=0.002). Further, the results of Mann-Whitney test showed that medical and surgical groups has the same level of survival (p=0.153). However, significant difference was observed between control and surgical groups (p=0.001), as well as between control and medical groups (p=0.022).As shown in p=0.0001). In addition, the Mann-Whitney test showed that medical and surgical groups had the same performance for angiogenesis (p=0.479). However, a significant difference was reported between control and surgical groups (p=0.0001), as well as between control and medical groups (p=0.0001). The mean inflammation was 2.08±0.95, 1.85±1.07, and 2.36±0.93 in surgical, medical, and control groups, respectively (p=0.337).As illustrated in ectively . In factThe present study aimed to evaluate the role of Montelukast as the medical delay of flaps. To this aim, the survival, angiogenesis, and inflammation of a randomized skin flap were compared between three equal groups based on surgical delay, medical delay, and control groups of Wistar rats. As it was already mentioned, surgical methods for delay flaps was a standard method of delay although may result in creating some adverse effects. In addition, finding good medical methods for delay may lead to better outcome for delay in flap applied surgeries. Based on the results, no significant difference was observed in the performance of survival, angiogenesis, and inflammation between surgical and Montelukast  group. Accordingly, Montelukast may be used alternatively with good expected results. However, the inflammation was the same between all three groups, which was regarded as the least affected factor by Montelukast.et al. reported that oral Montelukast in rats prevented from ischemia and reperfusion injuries in healing process of wound in colon anastomosis after superior mesenteric artery obstruction.8 This issue is considered as a possible explanation for higher survival in Montelukast group, compared with control group. In the study of Lafci et al., Iloprost and Montelukast therapies resulted in decreasing spinal injury after ischemia/reperfusion due to aortic clump, which may be evaluated in future studies regarding the possible drugs with synergistic effects; which may be used for medical flap delay.9Celik et al. reported the protective role of Montelukast on neuronal ischemic injuries.10 In addition, Zhao et al. emphasized that Montelukast resulted in protecting rat brain against focal transient ischemia due to the obstruction of middle cerebral artery.11 Based on the results of these two studies, the possible central role of Montelukast was observed, along with the peripheral function of this drug which can attenuate the observed effects. In another study, Oral et al. reported that Montelukast lead to a decrease in the effect of ischemia/reperfusion injury in ovaries of the rats in congruent with the findings in the present study.12Wang et al. showed that Montelukast resulted in enhancing the rate of angiogenesis and faster wound healing process.13 Further, according to Ozturk et al., Montelukast played the role of anti-oxidant leading to lower ischemia-reperfusion injury effects in testicular tissue in rats.14 Lower necrosis and higher survival can be regarded as indirect effects of this scavenging. In another study, Xu et al. demonstrated that CysLt receptor resulted in inhibiting angiogenesis. In addition, the inhibitors of this receptor such as Montelukast may lead to angiogenesis.15In addition, Turtay et al.16 indicated that Montelukast lead to lower ischemia/reperfusion injuries in hepatic tissue, which is in line with the results of flap delay process in the present study. Additionally, Daglar et al. emphasized a high potency of this medication for medical delay in flaps after the total obstruction of hepatic vessels in rats.17 In addition, Gideroglu et al. reported the lowered rate of ischemia/reperfusion injuries in axial skin flaps in rats by using montelukast, which is consistent with high survival in montelukast group in the present study.18Furthermore, Ozkan et al.19 in another study demonstrated higher VEGF and VEGFR and better angiogenesis rate, which is congruent with the results of clinical animal in this study. Further, the results of the present study is in line with the study of Gideroglu et al., which reported higher survival of random flap by using Montelukast at removing flap and up to six days.20 Finally, in another two studies by Sener and colleagues,21,22 good effects against ischemia-reperfusion injury in bladder and kidney tissues are in congruent with the findings for medical delay in flaps in the present study. In general, the results of the present study indicated good performance of Montelukast on survival and angiogenesis use of this medication for developing delay for skin flaps. However, further studies can be conducted in other animal models.Yang


Stroke is a major cause of disability worldwide, and balance impairments are common disabling factors in patients with stroke, leading to falls. Thus, the study objectives were as follows: (i) To find the prevalence of balance impairment among patients with stroke. (ii) To find out the factors associated with balance impairment in patients with stroke. This cross-sectional retrospective case control study involved eighty-one post stroke patients with a mean age of 58.36 ± 14.06, recruited from six hospitals, who underwent an assessment of balance, walking speed, depression and isometric strength of the ankle and knee. These patients were later categorized into subjects with good balance (<45) in the Berg balance scale (BBS) and those with poor balance (≥45), as cases and controls, to assess the factors associated with balance impairment using binary logistic regression. The prevalence of balance impairment among patients with stroke was 48.1%. The reduction in power of knee flexors (OR = 0.858), knee extensors (OR = 0.880) and ankle dorsiflexors (OR = 0.820) was found to be significantly associated with balance impairment, along with speed ), depression (OR = 1.331 (95% CI = 1.055–1.679)) and activities of daily living (OR = 0.313 (95% CI = 0.150–0.650)). In summary, around half of the patients with stroke exhibited balance impairments, with females being more prone. Stroke is one of the leading causes of mortality worldwide , and is Given the negative consequences of balance impairments in patients with stroke, it is thus critical to know the prevalence of balance impairment. Exploring the risk factors that are associated with balance impairment in patients with stroke can enable their easy identification, leading to prompt care.Multiple reports have been issued thus far on the prevalence of balance impairments post-stroke, with values ranging from 16.7% to as high as 83% ,22. DiffData on stroke in Saudi Arabia are evidently lacking, and this marked lack of evidence in the region regarding both the incidence and the prevalence of stroke has made the assessment of prevalence of post-stroke balance impairments even more difficult . With thThis cross-sectional retrospective case control study involved eighty-one subjects with stroke, and the sample was determined according to Kesley’s method, keeping the power at 80 and with a 95% CI. The subjects was recruited from four hospitals in Jeddah, Saudi Arabia. The inclusion criteria included the following: (a) patients who received a diagnosis of ischemic brain injury, or intracerebral or subarachnoid hemorrhage, by MRI or CT, with duration of 2 weeks or more since the onset of stroke; (b) patients who walk independently for 5–10 m with or without an assistive device; (c) patients who can follow simple instructions and sign the consent form; (d) patients who are 18 years of age and older. The following patients were excluded: (a) patients with orthopedic, cardiovascular, neurological or pulmonary conditions that may restrict assessment; (b) medically unstable patients; (c) patients with bilateral strokes; (d) patients with pre-stroke balance impairments; (e) ataxic patients.The general data included gender, age, type of stroke, side of weakness and time since stroke. The patients were also assessed for variables including balance, via the Berg balance scale (BBS). The BBS is a 14-item scale, requiring 10 to 20 min to complete and measure the patient’s balance, either statically or while preforming various functional movements. The items are scored from 0 to 4, with the score of 0 as an inability to complete the task and a score of 4 representing independent item completion. The muscle strength of knee flexors and extensors, as well as the strength of ankle dorsiflexors and plantar flexors, were measured using a handheld dynamometer (HHD). Speed was assessed via a timed ap and go (TUG) test, wherein the patient is timed while he/she rises from a chair with armrests and walks at a comfortable and safe pace to a marked point 3 meters away, then turns and walks back to sit down again. Activities of daily living were assessed using the Barthel index (BI), which measures the extent to which somebody can function independently and has mobility in their activities of daily living (ADL), i.e., feeding, bathing, grooming, dressing, bowel control, bladder control, toileting, chair transfer, ambulation and stair climbing. Level of depression was assessed via the geriatric depression scale (GDS), which is a screening test used to identify symptoms of depression in older adults, and the use of walking aids was also noted.Informed consent was obtained from the participants before they were enrolled in the study; ethical approval was obtained from the Centre of Excellence in Genomic Medical Research (04-CEGMR-Bioeth-2019), approved by the National Committee of Bioethics (KACST: HA-02-J-003).p value at p ≤ 0.05.The data were analyzed using statistical software SPSS version 21  and Graph Pad Prism version 6.0 . Mean, standard deviation, percentages, median, and range were used to describe the different characteristics of the participants. The prevalence of balance impairment was presented as a percentage. The significance of cases and controls is represented as odds ratio and Out of the 116 eligible subjects, 81 were included, with a response rate of 70%. The age of participants ranged from 25 to 94 years, with a mean of 58.36 ± 14.06. The basic characteristics of the study subjects are mentioned in A simple binary logistic regression analysis (Enter) method was done, keeping balance as the dependent variable to predict the influence of different independent variables. Odds ratio (OR) was used to find the influence of variables, keeping one of the dichotomous variables as the reference value. For the purpose of binary logistic regression, different variables were categorized dichotomously. (i) Balance; good balance (<45) and poor balance (≥45). (ii) Age; < 55 and ≥ 56. (iii) Gender; male and female. (iv) Side; left and right. (v) Type of stroke; ischemic and hemorrhagic. (vi) Duration; acute/subacute (<6 months of onset) and chronic (>6 months of onset). (vii) Aid; with aid and without aid. Cross-tabulation with a bivariate analysis was done to assess the effect of each variable on balance impairment, and significance was determined via chi square.The results of the binary logistic regression analysis showed that use of a walking aid, knee flexion and extension strength, ankle dorsiflexion strength, depression, speed and level of ADL are the variables that are significantly associated with balance impairment. Participants requiring a walking aid had a higher prevalence of balance impairment (77.8%), and were ten times more likely to have their balance impaired post-stroke in comparison to non-aid requiring patients (odds ratio (OR) = 10.8 (95% CI = 3.827–30.577)) . The strp ≤ 0.05) were further entered into logistic regression models with a forward stepwise (likelihood ratio) method, in which the probability of the entry of the variables was fixed as 0.05 and that of their removal as 0.10. Activities of daily living measured by the Barthel index was the only factor influencing balance impairment in the model  and good sensitivity and specificity on the receiver operating curve, with an excellent area under the curve value of 0.97 .Those factors found to be significant upon univariate analysis  . It is iThe current study has demonstrated that the stroke-related factors had a more significant relation with balance impairment than the sociodemographic factors. However, a variable relation between balance impairment and different stroke-related factors is noted in previous studies ,31,32, wGender differences showed that males were less likely to have balance impairments when compared to their female counterparts . Among tIn this study, the variables that have a significant relation with balance impairment are use of a walking aid, speed, knee flexion and extension strength, ankle dorsiflexion strength, depression, ADL and disability. These are considered to be modifiable factors; however, in previous studies, the factors that significantly influenced balance were mostly non-modifiable factors, such as age, gender, and post-stroke duration .The association of stroke with depression has been established in the literature, with almost 20% of stroke survivors experiencing depression in the acute stage . This, wThe limitations in this study include the male to female (3:1) ratio, with male participants being the larger group. The total sample size was also small for a prevalence study, due to the lack of information regarding the prevalence of stroke in the region, making the estimation of the proper sample size of the study difficult. Further case control studies are warranted with an age-matched population in order to address the ratio of difference between the controls and patients with stroke. In particular, longitudinal studies would be beneficial for addressing the long-term outcomes of balance impairment, the factors affecting it, and the influence of rehabilitation strategies on balance.Around half of the patients with stroke also exhibit balance impairments, with females having a greater incidence. Speed, depression, level of ADL, use of a walking aid, and the strength of ankle dorsiflexion, knee flexion, and knee extension were all found to be significant factors influencing balance in patients with stroke. As such, all these relations should be taken into consideration when planning rehabilitation in patients with stroke.