Burden disease related to chronic HBV infection is increasing worldwide. Monitoring Hepatitis B occurrence is difficult due to intrinsic characteristics of the infection, nonetheless analyzing this information improves strategic planning towards reducing the burden related to chronic infection. In this line of thought, this study aims to analyze national and regional epidemiology of Hepatitis B and it’s temporal trends based on Brazilian reported cases.Data obtained from the Brazilian National Notifiable Disease Reporting System (SINAN) from 2007 to 2018 were classified by infection status with an original classification algorithm, had their temporal trends analyzed by Joinpoint regression model and were correlated with gender, age and region.Of the 487,180 hepatitis B cases notified to SINAN, 97.65% had it infection status correctly classified by the new algorithm. Hepatitis B detection rate, gender and age-distribution were different among Brazilian regions. Overall, detection rates remained stable from 2007 to 2018, achieving their maximal value  in North region. However, there were different temporal trends related to different hepatitis B status and age. Women mean age at notification were always inferior to those of men and the difference was higher in Central-West, North and Northeast regions.Hepatitis B affects heterogeneously different populations throughout Brazilian territory. The differences shown in its temporal trends, regional, gender and age-related distribution helps the planning and evaluation of control measures in Brazil.The online version contains supplementary material available at 10.1186/s12889-022-14296-1. Viral hepatitis has significant worldwide burden, with increasing associated mortality. The Global Health Sector Strategy, states that understanding viral hepatitis epidemiology is key to the goal of eliminating it by 2030 .The Global Burden Disease Study analysis , showed Notwithstanding, good estimates of Hepatitis B Virus (HBV) infection rate are difficult due to the lack of good quality data and to the high frequency of asymptomatic or long-term chronically infected cases , 6.In order to analyze population features of infectious diseases, one must define the scale of the study. Local or specific population driven studies are more suitable to characterize risk factors related to the infection –10, whilBrazil is the fifth largest country in the world in terms of territory and population size  . It’s diThe 1988 Brazilian Constitution state that health assistance to the diseased is responsibility of Brazilian Ministry of Health (MoH), which incorporates an unified and nationwide health care system (Sistema Único de Saúde - SUS). The Health Surveillance Secretary is in charge of promoting surveillance and orienting health assistance and control strategic planning to decrease transmission of communicable diseases , 15. TheThe National Reportable Disease Information System (Sistema de Informação de Agravos de Notificação - SINAN), created in 1999, after the National System for Epidemiologic Surveillance , receives data of compulsorily notifiable diseases cases, which includes viral hepatitis , 16. CliIndividual Notification, including socio-demographic data pertaining to individuals and applying to all compulsorily diseases notifiable via SINAN;An epidemiological form, specific to each compulsorily notifiable disease or condition, including clinic, epidemiologic and laboratory data specific to it.The hepatitis surveillance system, launched with SINAN in 1999, provides nationwide clinical-demographic-epidemiologic data related to viral hepatitis including Hepatitis B. In this manuscript we analyze B hepatitis data from a SINAN extracted database, providing a detailed description of Hepatitis B occurrence, as related to its temporal trends, age, gender and regional characteristics in Brazil, discussing socio-demographic-epidemiologic determinants of its burden throughout the country.Hepatitis B data, from 2007 to 2018, extracted from SINAN database (SINAN Net – Version 5.0) anonymized, cleaned, reviewed and consisted constituted the study database. This study used the following SINAN Viral Hepatitis variables:A study defined indexing number – serving as an index variable for the database;dates of birth, first symptoms and notification;state of notification;gender;serological markers of HBV infection – Anti-HBs, HBsAg, Anti-HBe, HBeAg, Anti-HBc total and Anti-HBc IgM – referred to as Reagent, Not-reagent, Undetermined and Not realized.HBV Class 1, following the current Brazilian and European recommendations for HBV case definition [HBV Class 2, originally proposed here, modifying HBV Class 1 definition to make it more congruent with the actual notification practice in Brazil. The proposed HBV Class 2 definition is:Two other variables aiming to classify Hepatitis B infection status were included in the database. First, finition . Second,Infected: any serological marker for HBV infection;and Anti-HBc IgM positive;Acute: HBsAg positive and (Anti-HBs negative or undetermined or not informed);Chronic: HBsAg positive or Anti HBs positive) and (HBsAg negative or undetermined or not informed).Resolved:  by gender and infection status allowed the analyses of absolute and age-related temporal trends.p < 0.05), otherwise the term ‘stable’ was used.Data fitted to a Joinpoint Regression Model selected by Bayesian Information Criteria (BIC)  allowed The Welch Two Sample T-test for means with unknown variances compared gender differences of the mean age at notification among different Brazilian regions. In addition, One-way ANOVA with Bonferroni tests compared regional differences on the mean age at notification by gender. Together, both analysis allowed a better description of the different regional patterns of HBV population dynamics in Brazil. Statistical significance level was set at 5% (a = 0.05). The TBCO Statistica 13.5.0.17 and the Joinpoint Trend Analysis 4.9.1.0 software were used for analysis.HBV Class 1 classified HBV infection status of only 237,034 cases (48.65%), while HBV Class 2 allowed the identification of HBV infection status in 475,759 cases (97.65%). See Table In the 2007–2018 period, 487,179 identified cases of HBV infection were included in the analysis. Kappa value of 0.312 (95% CI: 0.311 to 0.314) when considering all cases in the database, including those non-classified by either classification variable. However, this poor agreement mainly reflects the lack of classified cases by HBV Class 1 .Concordance analysis demonstrated only a poor agreement between both case definitions criteria, with a Kappa = 1.0), meaning that HBV Class 2 correctly classified all cases classified by HBV Class 1.When considering only cases simultaneously classified by both variables , the agreement was perfect , unless interpreted in association with other serological, pathological, molecular or clinic-epidemiological markers, as the presence of HBsAg positivity should preclude the classification of Resolved. Table In addition, the 4.119 cases classified as Infected, Chronic and Resolved cases remained stable, but decreased for Acute cases, from 2007 to 2018. Trend analysis grouped by age intervals showed that the incidence of HBV Infected cases in Brazil decreased from 2007 to 2018 for the ages 1–9, 10–19 and 20–29, remaining stable for the others.Trend analysis showed that the incidence of Brazilian HBV Acute cases, the incidence decreased from 2007 to 2018 for all 10-years age intervals between 1 and 9 years and 30–39 years. For ages above 40 and bellow 60 years old, the incidence remained.For Chronic cases decreased from 2007 to 2018 for the ages bellow 30 years, and increased for those older than 40. Finally, the incidence of Resolved cases decreased for ages bellow 50.The incidence of Figure Hepatitis B distribution is heterogeneous in Brazil. From 2007 to 2018 the Southeast region notified 218,320 (45.88%), South 96,215 (20.22%), North 73,474 (15.44%), Central-West 49,323 (10.36%) and Northeast 38,427 (8.1%).Infected from 2007 to 2015, peaking at 53.01 cases per 100,000 inhabitants in 2011. However, from 2011 onwards its incidence consistently decreased, being surpassed by region South from 2016 on, as shown in Fig. In contrast, the North region reported the largest Chronic HBV cases notified in South  and Northeast  regions, as compared to its proportion in Brazil . Table S2 in Supplementary Material exhibits details of this analysis.Another aspect worth mentioning is the higher proportion of Infected and Chronic age-distributions from 2007 to 2018.Figure In Fig. The second pattern, seen in North, Northeast and Central-West, shows a considerable shift to the left on the age-related distribution of females as compared to males for ages below 30–40 years, being more pronounced bellow 30 years.Chronic infections in Northeast, 7.38 years , and Central-West 7.62 years , in contrast to Chronic infections in South, 3.76 years (95% CI 3.52–4.00) and Southeast, 3.71 years (95% CI 3.47–3.95). See table S3 of Supplementary Material for details.In addition, South and Southeast regions (first pattern described above), age difference between males and females are smaller as compared to North, Northeast or Central-West (second pattern above) for any HBV infection status. The most pronounced age difference occurs in Chronic females and 7.88 years  for Chronic males when comparing North region with Southeast region. For the complete analysis see table S4 of Supplementary Material.Age differences on the mean age at notification by region and gender shows that people living in the North, Northeast and Central-West regions are infected earlier in life than South and Southeast. The most pronounced finding is the age difference of 10.3 years  for In Brazil, as in other countries, national regulations define which diseases are of compulsory notification and how to report them to the official notification system. Infection diseases surveillance systems are essential to guide health politics on national and regional scales but have limitations due to under notification. Several different reasons contribute to this, like failure in diagnosing the disease, in reporting the occurrence of disease to local health authorities, in limited technical or administrative structures, limiting the information flow between local and national systems, among others , 21.Under notification may lead to under estimations of the true incidence or prevalence of a given disease. However, a careful analysis of the reported cases allows the identification of space, time and/or age related variations in the notification rate that can indicate changes in infection dynamics .The Brazilian viral hepatitis notification system exists since 1998. During implantation, from 1998 to 2004, several improvements occurred allowing a better performance of the system as a whole. From 2007 to 2018, the system became stable and, consequently, changes in epidemiologic parameters of HBV infection may reflect changes in real infection dynamics.Acute cases decreased for all age groups in the analyzed period  living in the endemic Amazon region . In 1998In addition, other important hepatitis control measures adopted by Brazilian Health Authorities derive from the HIV/AIDS Brazilian control program, promoting safer sex practices and delivering condoms syringes and needles, under certain conditions, to at risk populations since early 2000 .The effects of nationwide vaccination program and control measures in the incidence of HBV infection is also described in countries that, as Brazil, implemented Hepatitis B vaccination program around the year 2000 .Chronic, Acute and Resolved cases differs greatly among regions. South and Northeast regions have the largest proportions of Chronic cases. This results deviates from the national proportion of Chronic cases and suggests that the burden of HBV Chronic infection is greater in this regions. The results of the Global Burden of Disease in Brazil [As mentioned in Results, the proportion of n Brazil  shows thThe higher burden associated to HBV infection in these regions can be explained by HBV genotypes. To date, 10 HBV genotypes (A to J) have been identified, been genotype A and C associated with increased risk of chronicity and genotypes C and D with increased risk of liver cancer . In BrazAs long as chronic Hepatitis B is considered, the notification increase for those above 40 years-old seen from 2007 to 2018 in Brazil has also been described in China and USA , 29. As Similarly to those countries, Brazil has also experienced a reduction in mortality rates of cirrhosis and liver cancer in the last decade , 31 consHowever, the hepatitis B program are limited and, therefore, can diagnose and treat yearly only a fraction of people chronically infected with hepatitis B. Moreover, untreated chronically infected people may infect new partners who can evolve to unnoticed chronic infections. In addition, there is a suggestion that HBV vaccination immunity can wane after long periods of time , what coAs described, individuals from South and Southeast acquire Hepatitis B later in life when compared to the other regions. Also, males and females age-related infection rates in this regions are similar, in contrast to North, Northeast and Central-West regions. South and Southeast regions have lower Gini index, lower infant mortality rate, lower women fecundity rate, higher maternal age at firstborn and higher life expectancy at birth when compared to North, Northeast and Central-West regions , 33. ThiThis study have strengths and limitations. As off strengths, the proposed case definitions are less restrictive allowing the analysis of a much larger number of cases, although keeping a strict correlation with official HBV status classification Table . The anaIn addition, the analysis performed in this manuscript highlights the use of gender related age distribution, a parameter rarely explored in literature, but of upmost importance for understanding the infection dynamics in a given population.Infected individuals, suffering from under-notification. In addition, many observations are incomplete, while some are duplicated, making troublesome, but extremely necessary, a careful revision of data extracted from SINAN. In addition, even with this careful approach the completeness and correction of data cannot be fully warranted. Notwithstanding, as shown in this work, it is possible to recover significant information on disease dynamics even from such incomplete notification database registries.Limitations of this work relate to the quality of available data. The Brazilian Viral Hepatitis database includes only a fraction of the total HBV The analysis performed in this article demonstrates changes in notification rates of Hepatitis B, possibly reflecting differences in national health politics, vaccination programs and universal access to treatment. In addition, regional differences suggest that North, Northeast and Central-West populations are at higher risk to acquire HBV infection earlier in life and develop chronic infection; therefore, vaccination programs should prioritize these regions. Finally, gender differences points to a higher female vulnerability that have to be taken into account on control programs in the less developed Brazilian regions.Below is the link to the electronic supplementary material.Supplementary Material 1


The technical success rate of selective biliary cannulation in the TPS group was 91.8%. The spontaneous dislodgement rate of the prophylactic plastic stent was 98.4%. In conclusion, an unflanged pancreatic stent (4F × 5 cm) placement in TPS for patients with failed standard cannulation technique is a safe and effective measure due to low adverse events and few additional endoscopic procedures for removing the pancreatic duct (PD) stent.Prophylactic pancreatic stenting effectively reduces the rate and severity of post-ERCP pancreatitis (PEP) in the precut technique; however, studies on the optimal type and duration of the stent are still lacking. This prospective study evaluated the incidence and severity of PEP and the rate of spontaneous stent dislodgement in patients undergoing transpancreatic precut sphincterotomy (TPS) accompanied by prophylactic pancreatic stenting with an unflanged plastic stent (4F × 5 cm) for difficult biliary cannulation. A total of 247 patients with naïve papilla were enrolled in this study, and data were collected prospectively. In the final analysis, 170 and 61 patients were included in the standard cannulation technique and TPS groups, respectively. The incidence of PEP in the standard cannulation technique and TPS groups was 3.5% and 1.6% ( Endoscopic retrograde cholangiopancreatography (ERCP) is the preferable procedure for treating biliary tract diseases; however, it is frequently associated with serious post-ERCP complications. Post-ERCP pancreatitis (PEP) is the most common of these complications and can occasionally be fatal in severe cases. Selective biliary cannulation is key in performing endoscopic retrograde cholangiography (ERC) without complications, particularly PEP. However, several large studies have identified failure of selective biliary cannulation as an independent risk factor for PEP ,2,3,4, oIf selective biliary cannulation using the standard cannulation technique (SCT) fails, many endoscopists prefer an early switch to the needle-knife precut (NKP) technique because of concerns that prolonged attempts of SCT will increase the incidence of PEP and delay the procedure. The NKP techniques are representative of NKP sphincterotomy and fistulotomy and showed a lower rate of PEP when compared with prolonged attempts of SCT in meta-analyses ,13. In oThe pancreatic duct guidewire (PGW) placement is a technique for gaining access to the bile duct in patients in whom SCT fails, with the double guidewire technique (DGT) and TPS representatively used . Since tWhether increased PEP rate is related to the precut technique, repeated, or prolonged papillary manipulation, or repeated pancreatic cannulation remains unclear. However, the sole use of the above-mentioned advanced techniques results in a higher incidence of PEP than SCT in unselected patients ,25,26,27Nevertheless, studies on the optimal types and insertion duration of a PD stent for PEP prevention are lacking. In addition, an additional endoscopic procedure for removing the PD stent may be required, as it causes considerable burden and inconvenience to the operator and patient. There is no study on how to induce safe spontaneous dislodgement without complications. Here, we hypothesized that TPS would facilitate opening to the bile duct in patients with difficult biliary cannulation, reduce the incidence of PEP when accompanied by prophylactic PD stenting, and induce spontaneous dislodgement of the prophylactic PD stent. Therefore, this prospective study aimed to evaluate the incidence of PEP and the rate of spontaneous stent dislodgement in patients undergoing TPS accompanied by prophylactic PD stenting with an unflanged PD stent (4F × 5 cm).This single-center, prospective cohort study was approved by the institutional review board of the Daejeon St. Mary’s Hospital, the Catholic University of Korea. Between September 2018 and June 2021, a total of 353 ERCP procedures were performed on patients with naïve major papilla. After excluding patients with pre-ERCP hyperamylasemia, acute or chronic pancreatitis, pancreatic cancer, tumors of the major duodenal papilla, coagulation disorders, and history of bile duct surgery, 247 patients were enrolled, and their data were collected prospectively. Standard wire-guided biliary cannulation was performed in 180 patients, and selective biliary cannulation through a TPS was attempted in 67 patients with difficult biliary cannulation. Finally, we analyzed 61 patients in the TPS group and 170 patients in the SCT group, excluding cases of unintentional instrument insertion or contrast injection into the PD, when the procedures did not meet the study protocol, or when patients were lost to follow-up .The SCT was defined as guidewire-assisted biliary cannulation without contrast injection using a sphincterotome or standard ERCP cannula . TPS wasBased on a consensus document proposed by Cotton et al. , mild PEThe primary outcome parameter was the rate of PEP in patients undergoing a TPS. The secondary outcome parameters were the rate of other ERCP-related complications such as post-ERCP hyperamylasemia, PSB, perforation, the overall success rate of selective biliary cannulation, and the rate of spontaneous dislodgement of PD stent in patients undergoing a TPS. Laboratory tests were performed the day before the procedure, 4 h after the procedure, and in the morning of the day after the procedure. Abdominal x-rays were followed on days 1 and 2, 2 weeks, and 2 months after the ERCP procedure to evaluate the dislodgement of the prophylactic PD stent.® 300 D; ERBE Elektromedizin, Tübingen, Germany) was used for cannulation and sphincterotomy. Prophylactic PD stent placement used a plastic stent  with a single pigtail on the duodenal side, a diameter of 4F, a length of 5 cm, and without an internal flange.All ERCP procedures were performed under balanced conscious sedation with a titrated dose of midazolam, pethidine, and propofol. Opioid analgesics, anticholinergics, protease inhibitors, and antibiotics were administered appropriately before and after the procedure. Two high-volume endoscopists who perform more than 200 ERCPs yearly  performeIn all patients, the SCT was always performed as the initial procedure. In difficult biliary cannulation, TPS was attempted as a primary rescue procedure if successful PGW placement was achieved. In failed selective biliary cannulation with TPS, NKP techniques were performed as alternative rescue procedures. The TPS procedure is as follows : First, p-values < 0.05 were considered statistically significant. Statistical analysis was performed using Statistical Package for the Social Sciences . Continuous variables are represented as mean ± standard deviation (SD), and categorical variables are represented as numbers and proportions (%). Comparison between groups was carried out using the independent sample t-test for continuous variables and χ2-test with or without Fisher’s exact test for categorical variables. We hypothesized that the incidence of PEP in TPS with prophylactic PD stent placement would not be inferior to the previously reported results of SCT. We estimated the sample size based on the study of Sofuni A. et al., which indicated that the incidence rate of PEP was 3.2% in patients with prophylactic PD stent placement. The expected number of patients was 64, with an alpha value of 0.05, a power of 90%, and a drop-out rate of 10%.Of the 247 patients enrolled in the study, 180 (72.9%) achieved selective biliary cannulation with the SCT and 67 (27.1%) did not. Of the 67 patients with difficult biliary cannulation, TPS was performed in 64 patients (95.5%) who had successful PGW placement within 10 min. NKP papillotomy was performed in three (4.5%) patients who had failed PGW placement. Finally, 170 ERCP procedures were classified as the SCT group, and 61 ERCP procedures were classified as the TPS group . The patp = 0.001). However, the overall incidence of PEP was statistically insignificant . Six of seven patients with PEP experienced mild grades, and all patients were discharged without an extension of their planned hospital stay. In the SCT group, one patient with PEP experienced a moderate grade with a 4d extension of hospital stay. There were no severe grades of PEP in either group.As shown in p = 1.00). Only three patients in the SCT group developed clinically significant PSB, and none in the TPS group. Of the three patients, two had mild bleeding that did not require a blood transfusion, and one had moderate bleeding requiring transfusion of two packed RBCs. Post-ERCP perforation and related death did not occur in the two groups. The overall incidence of PSB was statistically insignificant between the TPS and SCT groups . The highest rates of spontaneous dislodgement occurred between 2 and 14 d. The dislodgement rate was 65.6% (40/61 patients). The rate of spontaneous dislodgement by period was 8.2% (5/61) within 2 d, 65.6% (40/61) within 2 weeks, and 24.6% (15/61) after 2 weeks. One patient (4.0%) experienced failed spontaneous dislodgement, which was removed by endoscopy after 2 months . There wSince the advent of ERCP, selective biliary cannulation has remained a prerequisite for successful ERC and is one of the most technically challenging points. To date, selective biliary cannulation fails in 15–35% of cases with SCT alone, even when performed by experienced endoscopists ,43. In tVarious advanced cannulation techniques have been developed to overcome difficult biliary cannulation. Of these, the NKP is the most commonly used technique for accessing the bile duct, and has a high success rate; however, it also has high risks of ERCP-related complications, which are reported in 2–34% of patients ,46,47,48p < 0.001) in patients who did not [p < 0.001). The incidence of PEP in the TPS group was slightly lower than that in the SCT group . However, the incidence of PEP between the two groups was statistically insignificant. Therefore, we can infer that prophylactic PD stenting prevented the aggravation of PEP, although TPS increased the rate of post-ERCP hyperamylasemia caused by difficult biliary cannulation, placement of PD guidewire, and thermal injury by sphincterotomy. These results suggest that TPS, accompanied with prophylactic PD stenting, in difficult biliary cannulation is as safe as SCT in unselected patients in terms of PEP. The overall incidence of PEP is approximately 5–15% and 0.1–0.8% in severe cases ,50,52,53 did not ,36. Seve did not ,56,57 in did not ,59,60 in did not ,62,63,64 did not ,35,36,65For prophylactic PD stents, previous studies have demonstrated that stents of 5F diameter are more effective than 3F stents in preventing PEP ,67,68. AIn conclusion, our study demonstrated that TPS accompanied with prophylactic PD stenting for difficult biliary cannulation was safe in terms of reducing PEP, and was effective in increasing the success rate of selective biliary cannulation in patients with difficult biliary cannulation with few needs for endoscopic removal of the prophylactic PD stent. Therefore, endoscopists should first consider the TPS with prophylactic PD stenting as an effective rescue technique for difficult biliary cannulation.


The method was applied to determine Ag and Zn in microcapsule samples of different sizes (120 and 450 μm) after their preparation with and without chitosan. Prepared microcapsules, after characterization, were bonded to a polymer carrier by sol-gel procedure and the materials were characterized by FTIR spectroscopy and high-resolution optical microscopy. Significant differences were found in Ag and Zn levels between microcapsules samples prepared with and without chitosan. The results have shown that samples with chitosan had up to 20% higher levels of Zn than Ag: 120 μm microcapsules contained 351.50 μg/g of Ag and 85.51 μg/g of Zn, respectively. In contrast, samples prepared without chitosan showed larger overall variability: In microcapsules with a diameter of 120 μm, the amounts of antimicrobial metals were 98.32 μg/g of Ag and 106.75 μg of Zn, respectively. Moreover, 450 μm microcapsules contained 190.98 μg/g of Ag and 121.35 μg/g of Zn. Those quantities are high enough for efficient antimicrobial activity of newly prepared microcapsules, enabling the application of microcapsules in different antimicrobial coatings.Silver (Ag) and zinc (Zn) are very powerful antimicrobial metals. Therefore, in this research, a high-throughput, sensitive, and rapid method was developed for the determination of Ag and Zn in microcapsules using inductively coupled plasma mass spectrometry (ICP-MS). The sample preparation procedure employed simple microwave digestion of the microcapsules with 55.55%  Due to the increase in antimicrobial resistance to conventional pharmaceutical drugs, the World Health Organization has recognized this problem as one of the most important issues in world health protection. One of the recent solutions is silver that is very well known as an efficient antimicrobial reagent . Moreovew/w. [The microcapsules originated from the 1940s when the pharmaceutical and paper industries began introducing encapsulated products. The process of encapsulation contains several steps in which the active compound is surrounded by a natural, semi-synthetic or synthetic polymer shell coating, with a typical diameter between 2 and 2000 μm. The thickness of the walls surrounding the active species is usually 0.5–150 μm, with an average proportion of core between 20 and 95% w/w. . Over thw/w. . There aThe encapsulation process can vary under different physical and chemical methodologies, and the main approaches are physical methods of encapsulation: air suspension coating, coextrusion, rotating disk atomization, spray-drying or cooling, fluid coating, and centrifugal extrusion; or chemical methods of encapsulation: coacervation, evaporation of the solvent, in-situ polymerization, liposome technology, matrix polymerization, nanoencapsulation, and solvent extraction.The choice of a particular technique will define the final outcome results: the usage, inertness, release time, desired concentration of the active species, the mechanism of release, particle size, density and stability, and also the price of the final product. There are many advantages of microencapsulation, but the main one is protecting the sensitive active species with the controlled and targeted release, and prevention of degradation reactions such as oxidation or dehydration. The graphical presentation of the structure of the microcapsules is shown in To analyze small microencapsulated products, the precise and accurate analytical methods such as inductively coupled plasma mass spectrometry (ICP-OES), inductively coupled plasma optical emission spectrometry (ICP-OES), time of flight secondary ion mass spectrometry (ToF-SIMS), scanning electronic microscope (SEM), and others are the most appreciated ,5. In saIn cases when sensitive compounds are encapsulated, the problems could arise from the fact that valuable silver materials are available for analysis in very small sample amounts. Secondly, only accurate analytical methods may provide information on the concentration of silver nanoparticles or silver ions that are released from the microcapsule during prolonged contact with different environmental conditions ,7,8,9. FSecondly, microscopic methods such as AFM, SEM, or high resolution OM can be applied as non-destructive methods for the characterization of microcapsules ,15,16,17+ based on the separation techniques coupled with atomic spectroscopy, including extraction method, chromatographic method, cation exchange reaction (CER), and single particles (SP) detection [During complex quantification of silver nanoparticles in the presence of silver ions, proper quality control procedures have to be applied to detect and characterize the samples regarding their size and concentration. Laborda et al. showed that the unknown nature of the nanoparticles and small sizes with instrumental constraints limited the information achievable in the analysis of different consumer products, foods, and environmental or biological samples . Wang etetection . They shetection ,38,39. Ietection ,41, but etection .Trace element analysis is crucial for samples in which very small amounts of metals provide substantive effects on different strains of microorganisms ,44,45. ISince only accurate analysis can provide information on the chemical composition of microcapsules, a very important part of the analysis was the determination of the limit of detection (LODs). In this work, limits of detection for all elements of interest were expressed as three times the standard deviation of the blank solution and reached the following values: 107 μg/L for silver and 66 μg/L for zinc, respectively. As it can be seen from Unfortunately, the proposed methodology is destructive and demands a prior degradation of all samples. However, the advantages of ICP-MS are high throughput as well as fast and precise analysis of trace amounts of samples. Secondly, limits of detection in ICP-MS are much lower than in ICP-OES, which is extremely important in cases of samples in which minor and trace elements have to be determined in very small sample amounts available for the analysis. Therefore, the best choice is to perform fast testing by ICP-MS and then to monitor the leaching of particular silver ions by an independent method that provides speciation. In cases of more complicated samples that contain traces of analyte, the better choice would be GF-AAS, a method for single element analysis, but with limits of detection lower than in AAS and ICP-OES. Encapsulation was performed as previously described, and the samples were recorded under high-resolution optical microscope. The resulting microphotographs are presented in As can be seen from metil resistant Staphylococcus aureus (MRSA) and metil sensitive Staphylococcus aureus (MSSA) strains of microorganisms [Therefore, as a potential application in producing medical textiles, the microcapsules were in this investigation fixed to the textile carrier by sol-gel methodology and dip coating techniques, and the resulting material is presented in rganisms . In addirganisms ,45.Therefore microcapsules might enable a very efficient solution for application in hospitals. Furthermore, microencapsulation can be an indispensable part of the functionalization of other polymer materials, such are for example agrotextiles or geotextiles. Currently, although microcapsules can stay un-attacked during 25 to 30 washing cycles, processes such as ironing and drying can cause a dramatic reduction of the desired effects [3O4/CS-Ag microcapsules by Fourier transform infrared (FT-IR) spectra, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy [As can be seen from the troscopy . In additroscopy . Their rIn addition, we applied ICP-MS to determine the total Ag and Zn content of the samples to predict their full antimicrobial effects. ICP-MS is highly recommended as an excellent choice for the multi-elemental determination of metals in sample solutions with high precision and accuracy. It offered the possibility of determining the trace, minor and major elements in the same sample. SEMEDX analysis enabled detecting the microcapsules dimensions, distribution of Ag and Zn in the shell, and homogeneity of different components. The combination of both methods enables the complete characterization of antimicrobial microcapsules. In contrast, the levels of zinc are a little bit lower in samples prepared with chitosan (85.51 μg/g of Zn compared to 106.75 μg of Zn), which was expected since both the chitosan and zinc are a part of the shell of the microcapsules and not the compounds in their core.All ICP-MS results are presented in 3, 65%, 5 mL) and hydrofluoric acid . Their obtained results revealed excellent performance with recovery values of metal ions ranging between 99.33% and 105.67%.The efficiency of the quantitative determination of the trace element  amounts in samples strongly depends on the proper sample preparation. We applied the microwave digestion by mixing 2.5 mL of spectral pure nitric acid and 2.0 mL of hydrogen peroxide. The digestion was performed in one cycle with three steps until maximal temperature of 170 °C was achieved. This protocol is based on our previous research and is similar to the methodology of microwave digestion reported by Khan et al. . They opICP-MS spectra are shown in + ion consists of two peaks that are corresponding to the isotopes of silver. In addition, silver oxide as Ag2O+ can have different combinations of Ag and O atoms: 107Ag2O+, 107Ag, 109AgO+, and 109Ag2O+ [+ and 109Ag to 92Zr16O1H+. Therefore, in complex systems, this should be checked. However, in our case, the spectrum was free of all interferences. In addition, the zinc isotope ratios are as follows: 64Zn+/66Zn+, 67Zn+/66Zn+, 68Zn+/66Zn+, and 70Zn+/66Zn+. Zn oxides are found at 80 (64Zn16O+) and 82 (66Zn16O+), and ArZn at 104. In addition, ZnCl mass were found in the range of 99–105, while the isotopic peaks of ZnCl3− were at 168.84, 170.83, 171.83, 172.83, 173.82, 174.82, 175.82, 176.82, 177.82, and 178.82 m/z.As can be seen from the 109Ag2O+ . MoreoveThe size of microcapsules has a crucial role in their application and in vivo efficiency. Wang and Hu reported that microparticles larger than 100 nm can stay at the site of administration. They investigated the processes of lymphatic uptake and accumulation and found them to be the most significant between 10–80 nm . TherefoShekunov et al. recommend the AFM as a technique that provides information about the surface of microparticles by profiling the surface , while SWe successfully applied SEM, SEM-EDX, FTIR, and ICP-MS techniques for the characterization of microcapsules. From the obtained results we conclude that the range of the Ag and Zn metals was in correlation with the current limits necessary for antimicrobial effects according to the literature data, and this is the basis of our future steps in the preparation of powerful antimicrobial coatings for medical materials. In our further experiments, we plan to perform experiments with the monitoring of leaching quantities of silver and its release as active antimicrobial species.An inductively coupled plasma mass spectrometer, Agilent 7900 ICP-MS , was used for all measurements. The instrument was equipped with standard nickel sampling and skimmer cones, a standard glass concentric nebulizer, quartz spray chamber, and a quartz torch with a 2.5 mm id injector. Operating conditions were as follows: sample depth 10 mm; ORS mode NO GAS/He; nebulizer carrier gas flow rate 1.09 L/min; extract lens 1 was zero, and 2 was −190; RF power 1550 W; RF matching 1.80 W; spectral detection mode; and integration time 0.1 s. All the measurements were done in triplicates.All the reagents (nitric acid), silver nitrate, and silver nanoparticles , and 1000 μg/mL standards (Ag and Zn) used for this research work were of p.a. grade, supplied by Merck, Darmstadt, Germany. Ultra-pure nitric acid supplied by Merck, Darmstadt, Germany, and ultrapure water produced by NIROSTA  were used in ICPMS analysis. Textile samples used for functionalization were pure cotton and viscose materials intended for medical purposes.Microcapsule samples were prepared as sodium alginate samples that contained silver in their core. In contrast, the outer shell was made of zinc sulfate 7-hydrate, with and without the chitosan. Encapsulation was performed by the reaction of sodium alginate and calcium chloride that produced calcium alginate and sodium chloride, according to the reaction:After 30 min, the spheres were filtered, rinsed, and stored in a cool and dark place prior to the characterization, because otherwise they would disintegrate.A microwave digestion oven  was used to digest 25 mg of the microcapsule samples by 2.5 mL spectral pure nitric acid and 2.0 mL of hydrogen peroxide. The digestion was performed in one cycle with three steps until maximal 170 °C. After the digestion, the sample solutions without residues were diluted with ultrapure water and measured on ICP-MS. In addition, microcapsules with Au and Zn were, after preparation, analyzed by high-resolution OM microscopy.Microcapsules with Ag and Zn were applied on woven viscose textile materials by dip coating (sol-gel) procedure using GLYMO precursor and HCl acid as a catalyst. After the immersion, the samples were dried for 24 h at room temperature. After drying, the samples were heated for 60 min at 100 °C to obtain a uniform coating suitable for antimicrobial protection (self-sterilizing or hygienic coatings). Several parameters that have main effects on the thickness of the covering film during immersion were optimized in our previous investigations: the speed of immersion, concentration and related viscosity of solutions, the surface tension, and the sample dimensions .For SEM-EDX characterization of the microcapsules, a scanning electronic microscope TESCAN VEGA TS5136LS  equipped with an EDX detector was used.The characterization of microcapsules filled with antimicrobial metals is an important part in the characterization of medical products. Interaction between the core and the shell of microcapsules can significantly influence the desired product properties. Therefore, the information on the exact chemical composition of trace and minor compounds is very important. Additionally, minor or trace compounds present in the core of microcapsules are released in time and can cause degradation under inappropriate cleaning and drying procedures, which will cause more degradation and collapse of microcapsules. Therefore, the chemical analysis and determination of chemical composition is a crucial step in preserving valuable active compounds. This work showed that inductively coupled plasma mass spectrometry and high-resolution optical microscopy may be easily applied for this purpose.


Heart failure (HF) is a global health problem with high morbidity and mortality. Recently, the association between peak atrial longitudinal strain (PALS) and clinical outcomes of HF has gained increasing attention. Our aim was to systematically assess the prognostic value of PALS for adverse events in HF.PubMed, Embase, and Scopus databases were systematically searched from inception to 30 April 2022. Studies in which PALS was assessed to predict adverse outcomes in adult patients with HF were included. Study selection, quality assessment, and data extraction were performed independently by two authors. The primary endpoints were all-cause death and cardiac hospitalization.p < 0.001]. Each unit increment of PALS was independently associated with decreased risk for the primary endpoint . The addition of PALS significantly improved the predictive power of conventional risk models .Among 7,787 patients in 17 included studies, 3,029 (38.9%) experienced the primary endpoint. Patients with events had lower PALS than those without events , identifier [CRD42020185034].[ Heart failure (HF) is becoming a global health problem due to its high prevalence and incidence . DespiteThis study was reported in adherence to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statements. The PubMed, Embase, and Scopus databases were systematically searched from inception to 30 April 2022. The following keywords were used as search terms: “HF,” “atrial strain,” “atrial deformation,” and “atrial longitudinal strain.” References of included articles were manually searched to identify additional eligible studies. No language restrictions were applied. Specific search strategies for each database are detailed in All studies were screened by two independent authors according to the following inclusion criteria: (1) studies that included adult patients with HF, (2) LA strain was measured on STE, (3) prospective or retrospective studies in which death and/or cardiac hospitalization were defined as endpoints, and (4) LA strain was used as a continuous variable to predict adverse outcomes during follow-up. Studies in which LA strain was evaluated using cardiac magnetic resonance imaging (MRI) were excluded because of technical differences. Case reports, reviews, letters, and editorials were also excluded. When multiple reports were derived from the same data set, only the most recent or complete study was enrolled in this review.The primary endpoint was defined as a composite outcome of all-cause death and cardiac hospitalization that varied from worsening HF, stroke, myocardial infarction, atrial fibrillation, and heart transplantation.For the HF phenotype, we used the definitions from the 2016 European Society of Cardiology Guidelines . The diaThe peak positive longitudinal strain during the LA reservoir phase was defined as PALS, which was calculated by averaging the peak values of all LA segments from two- and four-chamber views or only four-chamber view as the european association of cardiovascular imaging (EACVI)/american society of echocardiography (ASE)/Industry Task Force recommended .Two authors independently extracted data and summarized them in a data extraction file. Any disagreement was resolved by consensus or by consulting a third author. The missing data of eligible studies were attempted to obtain from the original authors by e-mail. The studies selected in our meta-analysis were evaluated for methodological quality using the Newcastle-Ottawa Scale (0–9 points) based on selection, comparability, and outcomes.I2 measure was used to assess statistical heterogeneity among studies. I2 values of 25, 50, and 75% were represented as low, moderate, and high heterogeneity, respectively. We conducted a subgroup analysis to determine the impact of PALS on prognosis in patients with HFpEF, HFmrEF, and HFrEF. Sensitivity analysis was performed to exclude the effect of conference abstracts without complete published text on the overall pooled estimates. To assess publication bias, funnel plot and Egger’s test were chosen to examine the study distribution. The trim and fill analysis was further used to evaluate theoretical missing research studies because of publication bias. A bubble plot performed in R 4.0.2 displays the optimal cutoff value and area under the curve (AUC) from receiver operating characteristic (ROC) analysis in each study. RevMan 5.3  and Stata 14.0  were used to perform statistical analysis with two-tailed p-values. A p-value of < 0.05 was considered statistically significant.Data for continuous variables were pooled to calculate a weighted mean difference (WMD) and 95% confidence interval (CI). The WMD of PALS between patients with event and without event was separately computed and compared. The pooled hazard ratio (HR) and 95% CI of PALS per unit increase were calculated to evaluate their prognostic value for the primary endpoints. Forest plots were constructed to display overall effects using a random-effects model. The From the initial 833 papers screened according to the search strategy and retrieved from reference lists, 513 papers remained following the elimination of duplicates. In total, 85 studies were identified as potentially eligible after screening the titles and abstracts. Following the full-text review, 68 studies were excluded due to not meeting the inclusion criteria. Consequently, a total of 17 studies that included 7,787 patients with HF were analyzed in the final analysis , 13–23. Methodological quality assessment using the Newcastle-Ottawa Scale showed high scores (7 points or more) in the 17 studies enrolled in our meta-analysis . The stun = 13) were prospective cohort studies from single-center or multi-center. For the patient population, 4 studies reported only HFpEF, 1 reported only HFmrEF, 6 reported only HFrEF, and others reported mixed HF. The mean age ranged from 58 to 76 years, and 57.8% were men. Among the 11 studies that reported comorbidities, the most common diseases were hypertension (54.8%) and ischemic heart disease (39.0%). The mean baseline PALS among reported studies varied from 8.8 to 36.2%. During a follow-up time ranging from 3.3 to 60 months, 3,029 patients (38.9%) experienced the composite endpoint of all-cause death and cardiac hospitalization.p < 0.001, I2 = 88%) difference in PALS between the two groups, as shown in In total, 6 studies investigated the difference in PALS in HF patients with and without events. The PALS value for patients experiencing events was 13.7 ± 9.5%, while for those without events, it was 16.7 ± 10.9%. The pooled results showed that there was a 6.17%  for PALS (per 1-unit increase). Importantly, combining all multivariate HRs after adjustment in 9 studies, each unit increase of PALS contributed to a 4%  risk reduction for the primary endpoint. In subgroup analysis based on LVEF level, pooled HR in the univariate Cox model was consistent with those found in the overall analysis . Details about the predictive increment of PALS in the Cox hazard models are summarized in The addition of PALS to baseline risk models contributed to the increase of both the C-statistic and the net reclassification index (NRI), varying from 0 to 0.11 and from 0.12 to 0.45, respectively. The pooled NRI of PALS for predicting adverse outcomes based on 3 studies was 0.22  revealed no evidence of publication bias in the 9 studies reporting HR in the multivariable Cox model  based on LVEF. In this regard, the results appeared to be widely representative and applicable to a broad spectrum of patients with HF. LVEF is essential to phenotype and guides the treatment of patients with HF, with an inverse correlation to mortality . HoweverPreviously, several multivariable risk models based on demographic, biomarker, and imaging indicators have been developed to understand HF prognosis , 35, 36.Our meta-analysis revealed that patients with HF experiencing events presented worse PALS than those without events. The cutoff value of PALS for identifying high-risk patients has attracted much attention and has not yet been determined. We provided a reference range of PALS cutoff value, from 12 to 25%, based on the available pieces of literature. Notably, patients with HFpEF or HFmrEF seemed to have higher PALS cutoff values when compared with those with HFrEF. To our knowledge, such a comparison has not yet been reported. According to Park et al., an ordinal decrease of PALS at baseline was detected in patients with HFpEF, HFmrEF, and HFrEF . WhetherOur study has some limitations. First, this is a meta-analysis of observational studies. Inevitably, multiple variations in the clinical settings, population characteristics, follow-up time, and endpoint definition were all possible sources of heterogeneity across different studies. We used a random-effects model to correct for these variations. Subgroup analyses and sensitivity analyses were performed to analyze and eliminate the high heterogeneity in our study. Although heterogeneity still existed, our findings remained significant, implicating that the prognostic value of PALS appears to be suitable for a broad range of patients with HF. Second, the funnel plot revealed that some asymmetry due to a small number of enrolled studies reduced the power of this test. Third, while LV global longitudinal strain (GLS) was associated with adverse outcomes in patients with HF based on recent reports , the smaIn this meta-analysis, PALS was found to be an independent predictor for all-cause mortality and cardiac hospitalization in patients with HF. The addition of PALS to conventional risk models could improve the predictive power for clinical endpoints. Overall, these findings indeed emphasize the clinical application of LA mechanics by STE to detect high-risk patients and predict prognosis.The original contributions presented in this study are included in the article/FJ and WC: conceptualization. FJ, AC, and LF: study selection. FJ, AC, WC, and DZ: formal analysis. FJ and DZ: statistical analysis. FJ, AC, DZ, and LF: drafting of the manuscript. WC, DZ, and LF: critical revision of the manuscript. WC: funding acquisition. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background: Despite the availability of COVID-19 vaccines and the proven benefits of vaccinations outweighing the potential risks, hesitancy to accept vaccines and additional doses remains a persistent problem. Therefore, the purpose of the study was to investigate hesitancy, confidence, literacy, and the role of the multi-theory model (MTM) constructs in COVID-19 booster uptake. Methods: This cross-sectional study utilized a 52-item psychometric valid web-based survey conducted during the month of October 2021 to recruit a nationally representative sample of U.S. adults. Univariate, bivariate, and multivariate statistical tests were used to analyze the data. Results: Among the booster hesitant group , a significantly larger proportion of respondents were unvaccinated with the primary series , were among 18–44 years age group , single or never married , had lower education with some high school , and identified themselves as Republicans . The hesitant group had lower mean scores of vaccine literacy, and vaccine confidence, and had 19% lower odds of behavioral confidence than their non-hesitant counterparts . Conclusions: The findings of this study underscore the need of raising public awareness through effective multi-theory-model-based communication campaigns. By April 2022, globally, there were more than 500 million cases of COVID-19 infection and more than six million deaths due to COVID-19 . As the Researchers also have found that a booster dose of the vaccine provides effective protection against COVID-19-related symptoms and hospitalization . SpitzerDespite the availability of COVID-19 vaccines and the proven benefits of vaccinations outweighing the potential risks, hesitancy to accept vaccines remains a persistent global problem ,14. PeopTheory-based interventions in promoting behavioral health provide information regarding what factors contribute to targeted preventive health behaviors . The mulThis cross-sectional study utilized a web-based survey conducted during the month of October 2021 to recruit a nationally representative sample of U.S. adults. The data collection for this study was performed as a part of commercial services offered by Qualtrics, which utilizes the market research panels through specialized campaigns [n = (z)2p (1 − p)/d2 with a 95% confidence interval , a margin of error d = 5%, and the proportion of booster dose hesitancy among Americans was 38% based on the data reported by Yadete et al., in December 2021 [The sample was predetermined using the formula: ber 2021 . The estThe study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of the University of Nevada, Las Vegas (UNLV-2021-108 dated 4 October 2021). Detailed information about the study’s objectives, procedures, expected outcomes, and risk was provided to the participants so they could make informed decisions about their participation. Participants were also informed that participation was voluntary and that they could withdraw from the study at any time.The survey instrument used in this study consisted of 52 items related to vaccine confidence , vaccineThe MTM-based initiation was measured through subscales, including perceived advantages, perceived disadvantages, behavioral confidence, and changes in the physical environment . Perceivt-test, and Pearson’s correlation test) were used to describe the sample. In univariate statistics, 95% confidence intervals of proportion were calculated using normal approximation to the binomial distribution. Adjusted standardized residuals greater than 2 were considered significant cells for contingency tables larger than 2 × 2 chi-square analysis. A posthoc contingency table analysis using adjusted residuals (or Z scores) was performed to generate p values of multiple comparisons. Hierarchical multiple regression was run to determine if the addition of primary vaccination status, vaccine literacy, vaccine confidence, and MTM-based subscales’ participatory dialogue, behavioral confidence, and changes in the physical environment improved the prediction of initiating booster dose acceptability above demographic variables alone  and Statistical Analysis System (SAS 9.4) were used to analyze the data.Data were first cleaned and recoded for the analytical operations. All statistical assumptions, including the normality, homogeneity of variance, independence of residuals, and equal error variances, were assessed. Box plots were visually inspected to identify outliers in the data. Continuous variables are described as mean and standard deviation unless stated otherwise. Categorical variables were represented as frequencies and proportions. Univariate and bivariate analyses  of the respondents were either fully vaccinated with the primary series or not hesitant toward the booster dose (58.3%) . The mean = 209, 41.7%), a significantly larger proportion of respondents were unvaccinated with the primary series , were among the 18–44 years’ age group , single or never married , had a lower level of education with some high school , and identified themselves as Republicans , critical literacy , total vaccine literacy (44.36 ± 6.71 vs. 39.62 ± 6.42), and vaccine confidence index  (The results in < 0.001) .p < 0.001, d = 1.30  and directly correlated with behavioral confidence , changes in physical environment , age , vaccine literacy (r = 0.35 p < 0.01), and vaccine confidence . Behavioral confidence was directly correlated with the changes in physical environment , vaccine literacy , and vaccine confidence . The Cronbach alpha values of the entire scale and only the MTM scale were 0.83 and 0.82, respectively. The perceived disadvantages were inversely correlated with the vaccine confidence  and vaccine literacy . Vaccine confidence and vaccine literacy were also positively correlated with each other  = 12.411, p < 0.001; adjusted R2 = 0.629. The addition of primary series vaccination status, vaccine literacy, and vaccine confidence to the prediction of booster dose vaccination behavior (Model 2) led to a statistically significant increase in R2 of 0.200, F  = 20.605, p < 0.001. The addition of participatory dialogue to the prediction of booster dose vaccination behavior (Model 3) also led to a statistically significant increase in R2 of 0.063, F  = 21.785, p < 0.001. The addition of behavioral confidence to the prediction of booster dose vaccination behavior (Model 4) also led to a statistically significant increase in R2 of 0.174, F  = 91.327, p < 0.001.In relation to the hierarchical regression model , the fulAs shown in the Forest plot graph , after aBooster doses for COVID-19 vaccines in the US were approved in early Fall 2021, and by April 2022, more than 95 million American adults received a booster dose ,32. ThisThree notable findings of this study need greater consideration to understand COVID-19 vaccination hesitancy and to design appropriate interventions. First, as it relates to sociodemographic characteristics, younger and never married, African Americans, those with lower education, and Republicans were the most hesitant toward the booster dose. While these findings are disconcerting due to the high risk of COVID-19 infection and poor outcomes associated with the infection among some of these groups, they are not entirely surprising. Even before the COVID-19 vaccines were rolled out and also during the active rollout phase, some of these groups expressed hesitancy toward the COVID-19 vaccination calling for greater targeted and tailored vaccine-related communication for these groups ,34,35. SGiven the three notable findings of this study, evidence-based interventions based on effective communication strategies are warranted for communities. Until there is enough vaccination around the world to hinder the emergence of newer COVID-19 variants, in countries where boosters have been approved and vaccines are available, the public should be educated about the ongoing risk and severity of infections with new variants. Additionally, the public should be informed about the large-scale successful trials of booster doses and their efficacy and safety. In the published literature, most recommendations to increase uptake of COVID-19 vaccinations focus on primary series vaccination. However, results from our study indicate that these recommended strategies can be utilized with some changes based on the local context. For example, a popular model (C’s model for an increase in vaccination) suggests that local leaders, healthcare providers, and the mass media should emphasize the reduction in Complacency and Constraints, increase Confidence and Calculations in favor of vaccines, and promote Collective responsibility by Communication for a unique local Context with Comparative analyses of the risks of having COVID-19 infection versus COVID-19 vaccination. Such communication about booster doses should also consider the findings of our study and emphasize addressing public concerns  and increasing awareness about the availability and need for booster doses ,41,42,43The results of this study should be viewed in light of several potential limitations. First, our findings are restricted by all threats to the validity and reliability inherent to cross-sectional and survey study designs . Second, although the MTM is a comprehensive model, there could be other individual characteristics and influential factors that could have influenced study participants’ willingness to receive a booster dose for COVID-19  ,39. ThirThis study aimed to examine the role of hesitancy, confidence, literacy, and MTM constructs in COVID-19 booster dose uptake. The study showed that more than half of fully vaccinated Americans were hesitant toward receiving a booster dose of the COVID-19 vaccine. In terms of designing concerted communication interventions, it was found that it would be useful to target campaigns for younger, never married, African Americans, those with lower education, and Republican political affiliation. The communication interventions need to focus on building vaccine confidence and literacy. This can be achieved by designing interventions that are based on the multi-theory model (MTM) of health behavior change that operationalizes the constructs of participatory dialogue in which advantages of booster acceptance are highlighted over putative disadvantages, and behavioral confidence is built in a stepwise manner through role modeling and exploring sources of confidence, and changes in the physical environment being developed by initiating robust policies and making the boosters easily accessible and informing the public about them.


The prognosis of patients diagnosed using US during medical checkup was better than that of patients identified through symptomatic presentation of PC. US for asymptomatic individuals with PC might be one of the useful modalities for promoting better prognosis of PCs.Recent advancements in surgical and anti-cancer therapies have provided significant hope of long survival in patients with pancreatic cancer (PC). To realize this hope, routine medical checkups of asymptomatic people should be performed to identify operable PCs. In this study, we evaluated the efficacy of medical checkups using abdominal ultrasonography (US). We retrospectively analyzed 374 patients with PC at our institute between 2010 and 2021. We divided these patients into several groups according to the diagnostic approach and compared their background and prognosis. These groups comprised PCs diagnosed through (a) symptoms, 242 cases; (b) US during medical checkup for asymptomatic individuals, 17; and other means. Of the 374 patients, 192 were men (51.3%), and the median age was 74 years (34–105). Tumors were located in the pancreatic tail in 67 patients (17.9%). Excision ratio and 5-year survival rate were significantly better in group (b) than in (a) (58.8% vs. 23.1%,  Pancreatic cancer (PC) is the worst prognostic cancer, and its 5-year survival rate (5-SR) is approximately 7.1% and 10% in Japan and the United States, respectively . It is bThis retrospective study included 374 patients diagnosed with PC between April 2010 and June 2021 at the National Hospital Organization Kure Medical Center and Chugoku Cancer Center . The types of PC we included in this study were pancreatic ductal adenocarcinoma (PDAC), intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia, and IPMN associated with invasive adenocarcinoma. We excluded patients with neuroendocrine neoplasm, solid pseudo-papillary neoplasm, acinar cell carcinoma, mucinous cystic neoplasm, and pancreatic metastasis from other cancers. This study was performed in accordance with the Declaration of Helsinki and was approved by our ethics committee (No. 2022-24). Patients were not required to provide informed consent to the study because the analysis was performed using anonymous clinical data. For disclosure, the details of the study are posted on some walls in the National Hospital Organization Kure Medical Center and Chugoku Cancer Center.The height and body weight of the participants were assessed and any history of comorbidities , malignancies, alcohol intake or smoking and FH of PC were recorded. Patients underwent blood tests, abdominal contrast enhanced computed tomography scans (CE-CT), magnetic resonance cholangiopancreatography (MRCP), and endoscopic ultrasonography (EUS) during their first visit to our hospital. Further, they underwent fine-needle aspirations using EUS and/or pancreatic juice cytology using endoscopic retrograde pancreatography (ERP). Presently, we use positron emission tomography (PET) and hepatobiliary magnetic resonance imaging with gadoxate disodium for detecting distant metastasis. IPMN-derived carcinoma was differentiated from concomitant PDAC in IPMN based on an assessment of the continuity of the carcinoma and IPMN using imaging studies or pathological examinations. For diagnosis, we used surgical specimens and/or imaging examinations. For prognosis, we retrospectively collected data from medical records in our institute.We divided the patients with PC into eight groups according to how PC was diagnosed . These gWe analyzed the backgrounds, clinical stages, excision ratio, and prognosis of the participants and compared the differences between the symptomatic group and asymptomatic groups and between the symptomatic group and each of the other groups. 2) was border between skinny and normal.We collected the 259 patients with PC noticed by US medical checkup group (17 patients) and symptoms (242 patients). We analyzed the characteristics of resected cases among the 259 patients. In addition, we performed survival analysis for these 259 patients using Cox regression hazard model. The value of CA19-9, 425 (U/mL) and NLR, 3.5, was based on the median value of patients in groups 1, 2, and 7. The value of BMI, 17.5 . p < 0.05 was considered as statistically significant.Fisher’s exact test was used to compare categorical variables, and the Welch’s p < 0.001), earlier stage of PC , and higher excision ratio  than patients in the symptomatic group. In the asymptomatic group, CA19-9 and neutrophil to lymphocyte ratio (NLR) were lower and prognostic nutrition index (PNI) was higher than in symptomatic group .Patients in the asymptomatic group had significantly smaller tumor size . Further, NLR as a prognostic factor of PC was significantly better in the asymptomatic groups including the US medical checkup group compared with the symptomatic groups. The proportion of patients with early stage PC  and the excision ratio were significantly higher in each of groups 3–7 than in the symptomatic group. The excision ratio and proportions of stages 0, 1, and 2 were significantly higher in the US medical checkup group than in the symptomatic group .The median survival time (MST) in the symptomatic group was significantly shorter than that in the asymptomatic group , females (p = 0.045), IPMN-derived carcinoma cases (p = 0.03), patients with normal or high body mass index (BMI) , and patients with CA19-9 < 425 (p < 0.001). The multivariable analysis showed more resected cases in the US medical checkup group (p = 0.04), females (p < 0.01), patients with normal or high BMI , and patients with CA19-9 < 425 (p < 0.001)  .p < 0.01), with normal or high BMI (p < 0.01), with low CA19-9 (p < 0.001), and with low NLR (p < 0.01)  .p = 0.08)  . The proIn this study, we showed that PCs identified by US during medical checkup for asymptomatic individuals had better excision ratio and more excellent prognosis than that observed in PCs identified through symptoms. These results suggest that screening for PC using US in asymptomatic individuals might be one of the effective modalities for improved prognosis with the medical treatment of PC.Patients with PC have an extremely poor prognosis. Further, PC remains the fourth leading cause of cancer-related deaths in Japan and the United States, with increasing incidence rates ,10. ThusIt has been increasingly recognized that the prognosis of patients with early stage PC is favorable ,12, and In 2012, the 5-SR of resected pancreatic cancers in Japan was approximately 20% , neoadjuTypically, the effective way to detect cancers earlier might be cancer screening for asymptomatic individuals. Cancer screening is recommended by the Ministry of Health and Welfare of Japan for five cancers including lung, stomach, breast, colon, and uterus neck cancers, but is not recommended for pancreatic cancer. The recommendation for cancer screening may not only be due to the improvement of mortality but also the avoidance of unnecessary examinations and therapies. To identify PCs early, routine CE-CT, MRCP or EUS examination should be performed more than twice a year. However, US performed once a year might be a better modality for public pancreatic cancer screening, considering its non-invasiveness, ease of use, and lower cost. One additional advantage of US is the ability to find other abdominal cancers including liver, kidney, biliary tract organs, and urinary tract organs. The total numbers of these cancers are more than the total numbers of esophagus and stomach cancers in Japan . In thisCurrently, PCs are identified earlier  based onThinking from another point of view, the proportion of PDACs from the surveillance of patients with IPMN in this study was very low 12/374, 3.5%). Further, the lifetime carcinogenic rate of PC was reported at frequency of 2.6% in males and 2.5% in females [, 3.5%. FUS is effective for outpatient care because of its convenience and non-invasiveness. Its sensitivity and specificity ranges for detecting PCs are broad , and there are some differences according to operators, participants, and machines ,37,38,39The disadvantage of US is that its use in some location, especially in the pancreatic tail makes the findings difficult to describe. In our study, three tumors were located in the pancreatic tail, and all could not be described by US. Hepatic metastasis was detected in two of the 3 patients by US. Ashida et al.  reportedIn Onomichi city in Hiroshima prefecture and Yamanashi prefecture, clinics and medical examination centers work closely with referral centers, and the PC discovery rate has been increasing, and some patients with stage 0 and 1 are identified ,15,43,44Incident ratio of pancreatic cancer is rapidly increasing in individuals of 60’s and the incident ratio increase with age. In comparison with 50’s, the numbers of PCs are 3.3fold in 60’s, 4.5fold in 70’s, and 3.9fold in 80’s . Thus, pThere are several limitations in this study. First, this is a retrospective analysis in a single center, so there are small number of cases in the analysis, and there may have been single center bias. Particularly, majority of the patients with PC in our analysis were older than that observed in other high-volume centers because of the increasing aging population in Kure city. Second, we could not show the detectability of pancreatic cancer with US because most patients were diagnosed with CT and underwent EUS, not US, as additional examinations. Thirdly, there might have been a bias in the grouping of patients into the 8 groups because the groupings were based on reports from referral letters. Finally, we included patients who were diagnosed in past years, so there were some differences in the diagnostic modalities and standard therapy, which were based on the year in which patients were diagnoses and how these factors influenced prognosis.In 2019, The United States Preventive Service Task Force reported  that thePCs identified by US during medical checkup for asymptomatic individuals had more excellent prognosis than that observed in PCs identified through symptoms. The public should be educated about the importance of PC screening in asymptomatic individuals, and we need to accumulate the evideces that show efficacy of cancer screening for PC using any modalities such as CE-CT, MRCP, EUS, and US.


Evidence of hypersensitivity has been reported with ASV but not with Kounis syndrome. More so, various other vaccinations have also been associated with Kounis syndrome. We present the case of a 30-year-old male who presented to the emergency department with post-snake bite envenomation and neurological symptoms. After the initiation of the anti-snake venom, the patient’s neurological signs improved. However, the patient developed acute chest pain. His ECG showed transient ST elevation, and cardiac enzymes and serum IgE levels were raised. A diagnosis of Kounis syndrome was made, and the patient was managed accordingly.Kounis syndrome is the concurrence of acute coronary syndromes associated with allergic or hypersensitivity and anaphylactic or anaphylactoid triggers. Although it is not a rare diagnosis, the different presentations and afflictions of all ages, sex, and racial groups make it a diagnostic challenge. Various triggers include food types, environmental exposure, and drugs. Cases triggered by serum sickness, tetanus antitoxin, and snake bites have been documented in the literature. However, to the best of our knowledge, no case triggered by anti-snake venom (ASV) has been reported yet, as seen in our patient. ASV is composed of refined F(ab) Kounis syndrome has been established as the concurrence of acute coronary syndromes with conditions associated with the activation of mast cells, including allergic or hypersensitivity and anaphylactic or anaphylactoid triggers . Kounis Three variants of Kounis syndrome have been identified: vasospastic allergic angina (type I), allergic myocardial infarction (type II), and stent thrombosis (type III). In the type I variant, patients have normal coronary arteries, which are induced to spasm by an acute allergic reaction as a manifestation of endothelial dysfunction or microvascular angina . A varieA 30-year-old male (with no comorbidities) presented to the emergency department with an alleged history of a snake bite on the right foot around six hours after the incident with complaints of pain over the right foot, blurred vision, and difficulty speaking.2 of 98% on room air, a pulse rate of 62/minute, and a BP of 126/86 mm Hg. On further examination, there was the presence of ptosis and dysarthria; however, the single breath count was 30. Fang marks were observed at the base of the great toe on the right foot. A provisional diagnosis of snake bite with neurotoxic manifestations was made.The primary assessment revealed a patent airway, a respiratory rate of 20/minute, SpORoutine investigations, including blood gas analysis, a 12-lead ECG, a 20-minute whole blood clotting time, a complete blood count, kidney function tests, and a coagulation profile, were done. Two large bore intravenous accesses were obtained, and 10 vials of anti-snake venom (ASV) were diluted in 500 ml of normal saline to be given over 30 minutes after premedication with subcutaneous adrenaline (0.25 mg of a 1:1000 dilution). The first doses of atropine (0.6 mg) and neostigmine (1.5 mg) were also given in view of the neurological symptoms.The patient’s neurological symptoms showed improvement; however, 15 minutes after the completion of ASV, the patient suddenly developed sudden onset retrosternal chest pain, radiating to both arms and associated with sweating. The patient became hypotensive with a BP of 86/50 mm Hg, and his pulse became thready at a rate of 70/minute. About 200 ml of IV crystalloid  was given in a bolus over five minutes. A 12-lead ECG was taken immediately reported . Furtherreported .In our case, our initial dilemma was twofold: first, whether the cardiac ischemia was related to allergic vasospasm, and second, whether the allergic vasospasm was due to the anti-snake venom.Our patient’s 2D echo showed regional wall motion abnormality corresponding with the ECG findings favoring acute vasospasm rather than direct cardiotoxicity due to the snake bite itself. The highly raised IgE levels supported the presence of an acute allergic reaction. These features, along with the transient ECG changes and resolution of symptoms within 24 hours, would be characteristic of type 1 Kounis syndrome.The case highlights a rare complication of Kounis syndrome triggered by the administration of anti-snake venom in a patient with a confirmed neurotoxic snake bite. As primary treating physicians and, in most cases, the first responders, it is imperative for emergency physicians to be aware of such relatively rare albeit immediately manageable complications. Such complications occur more often than reported, thereby, are easily missed. An early and prompt diagnosis of such rare complications would largely benefit the patients by reducing their mortality.


The platelet-to-white blood cell ratio (PWR) has been reported to predict the severity of patients with various diseases. However, no previous studies have assessed the use of the PWR as a prognostic marker for pyogenic liver abscesses (PLA). This observational retrospective study was performed between January 2008 and December 2017, including 833 patients with PLA from multiple centers. The enrolled patients, on average, had a PWR of 17.05, and 416 patients had a PWR lower than 17.05. A total of 260 patients (31.2%) with PLA showed complications of metastatic infection, pleural effusion and abscess rupture. A low PWR level was identified as a strong risk factor for metastatic infection and pleural effusion. The low PWR group also had a longer hospital stay. In the multivariate analysis, old age, anemia, albumin and CRP levels and unidentified pathogens were significant factors for low PWR levels. A low PWR, old age, male sex, abscess size, albumin, ALP and unidentified causative pathogens showed significant associations with a hospital stay longer than 28 days. As a result, PLA patients presenting with a low PWR were shown to have more complications and a poor prognosis. Considering its cost-effectiveness, PWR could be a novel biomarker used to predict a prognosis of PLA. Klebsiella pneumoniae (K. pneumoniae) [Pyogenic liver abscesses (PLA) have a low and varying rate of incidence, depending on the countries in which it is measured, ranging from 1.1 to 4.1 per 100,000 in Western countries ,3,4 to 5umoniae) ,12 but aumoniae) . In clinumoniae) . HoweverRecently, hematological markers for the prognosis of several diseases have become an area of focus in research. The neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, red cell distribution width and mean platelet volume have been suggested to be inflammatory markers with prognostic value in various diseases ,16,17,18This observational retrospective study was performed between January 2008 and December 2017 at Hallym University Medical Center, which consists of 6 hospitals: Hallym University Sacred Heart Hospital, Hallym University Kangnam Sacred Heart Hospital, Hallym University Chuncheon Sacred Heart Hospital, Hallym University Hangang Sacred Heart Hospital, Hallym University Dongtan Sacred Heart Hospital and Kangdong Sacred Heart Hospital in Korea. The medical records of Hallym University Medical Center were systematically searched for code K75.0 of the International Classification of Disease, 10th Revision, to identify patients with PLA. Enrolled patients satisfied the following criteria: (1) compatible findings on ultrasound (US), computed tomography (CT) or magnetic resonance imaging (MRI) diagnosing PLA, (2) either positive culture results from blood culture or an abscess and (3) the resolution of symptoms after antibiotic therapy. Patients meeting the following criteria were excluded: (1) age < 18 years old and (2) diagnosis of parasitic/fungal/amoebic abscesses.The medical records were systemically reviewed, including clinical information on sex, age and underlying and current medical conditions. Patients with clinical symptoms indicative of cholecystitis, cholangitis or documented bile duct disease were considered to have PLA secondary to biliary tract disease. Initial laboratory values were collected on the first day of hospital admission or within 24 h after the clinical diagnosis of PLA if PLA was not the initial cause of hospitalization. Blood cultures were performed for all patients. If patients were treated with the percutaneous drainage or aspiration of the abscess, pus cultures were performed with the collected material. The PWR was calculated by dividing two values from the laboratory results. The PWR cutoff value for the low PWR group was selected based on the median PWR values of the total number of patients with PLA included in the study. Anemia was defined as a hemoglobin (Hb) level less than 13 g/dl in adult males and less than 12 g/dl in adult females.The requirement for informed consent was waived because this study was designed as a retrospective study, and the analysis used anonymous clinical data. This study was approved by the Ethics Committee of Hallym University Medical Center. The study was conducted with the approval of the Institutional Review Board of Hallym University Medical Center (2019-06-007-001). All methods were conducted in accordance with the relevant guidelines and regulations.The basis of treatment was antibiotic therapy and percutaneous drainage (PD) according to size and nature of PLA. All patients with PLA were treated promptly when PLA was suspected after at least one set of blood cultures were taken. Empiric antibiotic regimens usually consist of a third-generation cephalosporin, such as ceftriaxone, along with metronidazole. PD was performed when (1) the size of PLA was ≥ 5 cm, (2) the presence of hemodynamic instability was observed, (3) gas within the abscess cavity, regardless of size, was observed and (4) the failure of antibiotic therapy for PLA < 5 cm (5), a sign of impending rupture on radiologic imaging, was observed . The antp values < 0.05 were considered statistically significant, and all p values were two-tailed. Mortality was assessed by analyzing the Kaplan–Meier curves.The statistical analysis was performed using R, a language and environment for statistical computing  and SPSS version 24 software . Quantitative variables are presented as the means ± standard deviations (SDs). The skewness of the value was calculated, and values > −2 and <2 were considered evenly distributed, and the mean value was used as a representative value. Groups with skewed values who did not satisfy this standard were considered skewed, and the median value was used to represent that group. Welch’s two-sample test and Student’s t-test were used to analyze continuous variables by calculating the statistical results of the F test to compare the differences between two variables, and Fisher’s exact or Pearson’s chi-square tests were used to compare categorical variables. Factors that were significant in the univariate analysis were entered into a stepwise multivariate analysis to determine the independent risk factors. Odds ratios and their 95% confidence intervals were calculated. All p < 0.001). The low PWR group had significantly higher WBC counts and lower platelet counts than the high PWR group. The CRP level was increased in the low PWR group (206.8 ± 91.3 mg/dL) compared to the high PWR group (161.9 ± 340.7 mg/dL) (p = 0.01). Patients with a low PWR showed an association with hypertension (HTN), but no significant association was observed with diabetes mellitus (DM). Interestingly, the Hb levels differed between the two groups, in which patients with a low PWR had higher levels of Hb than patients with a high PWR . Albumin levels were decreased in the low PWR group compared with the high PWR group . Aspartate transaminase (AST) and alkaline phosphatase (ALP) levels were not significantly different between the PWR groups, whereas alanine transaminase (ALT) levels were increased in the low PWR group (96.0 ± 115.9 IU/L) compared to the high PWR group . The size and location of liver abscesses were analyzed for all patients who showed suspicious findings on radiologic exams. Of the 833 patients who had an abscess with an average size of 5.4 ± 2.8 cm, no significant difference in the abscess size was observed between the PWR groups . The location of the abscess was analyzed based on the lobes, and the most common site of occurrence was the right side, in 527 patients (63.3%), followed by the left  and both lobes . Similar tendencies were observed in both PWR groups, but the lower PWR group included a higher proportion of patients with abscesses on the left side than the higher PWR group  compared to the right side . The rate of occurrence in both lobes was not different between the PWR groups . One hundred and eighty-one patients (21.7%) with PLA experienced complications, including metastatic infections, such as septic endophthalmitis or pneumonia, pleural effusion and abscess rupture. The PWR of patients with complications was calculated as 18.6 ± 19.6 with a WBC count of 14.78 ± 7.04 × p < 0.001, 50.8% vs. 43.9%; p = 0.0014), including septic endophthalmitis  and pneumonia . However, the opposite trend was observed for pleural effusion between the PWR groups . The incidence of abscess rupture between the low and high PWR groups was not significantly different . Causative pathogens were identified in 622 of the total of 833 patients. K. pneumoniae was the predominant pathogen, accounting for 48% of all infections (400/833). Interestingly, K. pneumoniae was detected as the causative pathogen in 56.3% of patients with PLA presenting with a low PWR compared to 39.8% of patients with PLA presenting with a high PWR . However, a significant difference in the identification of Escherichia coli (E. coli) was not observed between the low PWR and high PWR groups.Among the total of 833 patients enrolled in the study, the median PWR of all patients with PLA was 17.05 (range: 0.12-237.40). Considering the left-skewed distribution of PWR (skewness 4.01), an adequate cutoff value for a low PWR was determined as the median value. The baseline characteristics of the enrolled patients are shown in K. pneumoniae infection and unidentified infection were significant factors contributing to the development of low PWR levels. In the multivariate analysis, an old age > 65 years, anemia, albumin and CRP levels and infection with unidentified pathogens were significant factors contributing to low PWR levels (odds ratio (OR) 1.918; 95% confidence interval [p < 0.001, OR 0.423; 95% CI 0.288–0.615; p < 0.001, OR 0.617; 95% CI 0.447–0.844; p < 0.001, OR 1.0005; 95% CI 0.999–1.002; p < 0.001, OR 0.545; 95% CI 0.334–0.833; p = 0.014, respectively). However, no significant associations were observed between sex, DM, abscess location, AST levels, ALT levels, ALP levels, PT-INR, Cr levels, causative organisms of K. pneumoniae or E. coli and low PWR levels in patients with PLA.We performed univariate and multivariate logistic analyses to investigate the factors related to a low PWR in patients with PLA . In the interval  1.330–2.K. pneumoniae and unidentified infection were associated with the development of metastatic infection. In the multivariate analysis, a low PWR level was significantly associated with the development of metastatic infection . However, age, HTN, DM, the location and size of the abscess, levels of albumin, AST, ALT, ALP, PT-INR, Cr, and CRP and infectious pathogens did not show significant associations with the development of metastatic infection in patients with PLA.We performed univariate and multivariate logistic regression analyses of patients with PLA to reveal the risk factors for the development of metastatic infection in detail . In the E. coli infection and infection with an unidentified organism were associated with the development of pleural effusion. In the multivariate analysis, a low PWR, ALP level and infections with an unidentified organism were associated with pleural effusion . Other factors, including age, HTN, DM, the location and size of abscess, anemia, levels of albumin, AST, ALT, PT-INR, Cr, and CRP and infections with K. pneumoniae, E. coli and other organisms were not correlated with the development of pleural effusion.Additionally, univariate and multivariate logistic analyses were performed to identify the risk factors for the development of pleural effusion . In the p = 0.99). Because the survival probability of the total group was very high at all time intervals, we focused on the trends between the groups but not the actual probability. The low PWR group showed an acute decrease in the probability of survival at approximately day 60, with a survival probability of approximately 70% in the normal PWR group on day 87. This implies a trend of a decreasing survival probability in patients with a low PWR.The mortality rates of the low PWR group and high PWR group are compared in p = 0.001) and 28 ).Patients were also stratified by the length of the hospital stay, and the results are shown in K. pneumoniae infection and unidentified infection were associated with prolonged hospitalization for more than 14 days. In the multivariate analysis, a low PWR, abscess size, and levels of ALP and CRP showed correlations with prolonged hospitalization for more than 14 days . The remaining factors did not significantly affect the number of HDs.We conducted univariate and multivariate logistic regression analyses of the subgroups . The remaining factors did not significantly affect the length of hospitalization. Interestingly, patients with PLA requiring hospitalization for more than 28 HDs were specifically characterized by older age, male sex, a low albumin level and infection with unidentified pathogens compared to those requiring hospitalization for longer than 14 HDs.For patients who were hospitalized for more than 28 days, the univariate logistic analysis revealed that a low PWR, older age, male sex, abscess size, levels of albumin, ALT, and ALP, infection with K. pneumoniae [K. pneumoniae infection is well known as a risk factor for the development of metastatic infection, we did not observe any statistically significant association based on the multivariate analysis. Thus, a lower PWR state renders the patient susceptible to the spread of bacteria. Based on this result, we might recommend testing for metastatic infection earlier in patients with PLA presenting with a low PWR.The risk factors for a poor prognosis of patients with PLA are well-known, including multiple abscesses, associated malignancies, jaundice, hypoalbuminemia, leukocytosis, bacteremia and eumoniae ,28,29,30eumoniae ,24,25,26In addition, pleural effusion, which develops in approximately 20-50% of patients with PLA, causes considerable distress to patients during treatment ,33,34,35K. pneumoniae was not significantly associated with a low PWR in the multivariate analysis, K. pneumoniae was a major causative pathogen in the low PWR group (56.3%) compared to the high PWR group (39.8%). The relationship between lower platelet counts and K. pneumoniae infection indicates the importance of understanding the role of vascular interactions, especially the role of platelets, in determining the prognoses of diverse medical conditions. Previous studies also noted that thrombocytopenia is a sign of severe infection, which may be explained by diverse cell receptors, such as Toll-like receptors, And its role in activation of neutrophils. The finding that platelets activate the antibacterial mode of the neutrophils and form neutrophil extracellular traps also provides a reason for placing clinical emphasis on thrombocytopenia [K. pneumoniae. This result is consistent with a previous study, showing that a blood-culture-confirmed bacterial infection and thrombocytopenia were associated with a poor prognosis [According to previous studies, the cutoff value for PWR is 20 in patients who undergo splenectomy for trauma, as a reliable marker of infection , and 26 ytopenia . Despiterognosis . The mecWR group .8%. The K. pneumonia PLA. Although our data did not show a significant difference in the mortality rate between K. pneumonia PLA and culture-negative PLA (data were not shown), Chan et al. demonstrated that K. pneumonia PLA has a lower mortality rate than non-K pneumonia PLA in a systemic review and meta-analysis [K. pneumonia PLA and culture-negative PLA have several demographic and clinical differences, and that the overall outcomes of culture-negative PLA patients are similar to those of K. pneumonia PLA patients if they receive an appropriate antibiotic treatment and PD [PWR was not statistically associated, to a significant extent, with the mortality of patients with PLA, and statistical significance was difficult to determine, as only 34 patients died. However, in the analysis of factors related to the length of the hospital stay, the PWR was revealed as an important risk factor. A higher percentage of patients requiring prolonged hospitalized showed a low PWR after both 14 days and 28 days. Based on these results, the PWR may offer a prognostic factor and evaluation measure for infectious diseases, specifically for patients with PLA. The risk factors for requiring hospitalization for more than 28 days were a low PWR, older age, male sex, size of the abscess, levels of albumin and ALP and infection with unidentified causative pathogens. Albumin is one of the factors used to measure the liver synthesis rate, but it is also affected by malnutrition. Hypoalbuminemia may be caused by inflammation, hepatocyte damage, decreased albumin synthesis, the dietary insufficiency of amino acids or increased excretion of albumin . Hypoalbanalysis . Howevert and PD . Therefot and PD ,11,14,42K. pneumoniae. Secondly, while this study population was relatively large, we were unable to identify a risk factor for mortality due to the low number of deaths . Thirdly, we were unable to confirm the baseline PWR level of the included patients before the development of PLA. Additionally, a meaningful PWR cutoff value remains to be determined. Therefore, our cause-and-effect relationship of PWR in patients with PLA may not be coherent, and further prospective multicenter studies are still needed in order to verify the role of PWR. Further prospective studies are needed in order to investigate whether a more aggressive treatment for patients with PLA presenting with a low PWR would be beneficial.This study has some limitations. Firstly, it was a retrospective study, and we were unable to determine the virulence factors, such as the serotypes of In conclusion, patients with PLA presenting with a low PWR exhibit worse clinical manifestations, more complications and a poorer prognosis. The PWR level may be used to measure the disease severity and predict the prognosis of patients with PLA. Since the development of metastatic infection and pleural effusion occur at a higher rate in patients with PLA presenting with a low PWR, the regular monitoring of the PWR might be useful for detecting complications earlier and improving the patient’s prognosis. Considering its cost-effectiveness, PWR could be a novel biomarker used to predict complications and a poor prognosis of PLA.