The aim of this study was to evaluate changes in aortic growth rate and factors influencing aneurysmal dilatation after uncomplicated acute type B aortic dissection (ABAD).Medically treated patients with uncomplicated ABAD between September 2004 and January 2020 were retrospectively reviewed. Diameters of 6 different sites in the descending aorta were measured and aortic growth rate was calculated according to the time interval. Factors associated with aneurysmal changes were also investigated.P = 0.021) and a proximal entry >10 mm  on initial computed tomography imaging.This study enrolled a total of 105 patients who underwent >2 serial computed tomography with a mean follow-up duration of 35.4 (12.1–77.4) months. The mean overall growth rates of the proximal descending thoracic aorta (DTA), mid-DTA, distal DTA, proximal abdominal aorta, maximal DTA and maximal abdominal aorta were 0.6 (1.9), 2.9 (5.2), 2.1 (4.0), 1.2 (2.2), 3.3 (5.6) and 1.4 (2.5) mm/year, respectively. The growth rate was higher at the early stage. It decreased over time. Growth rates of proximal DTA, mid-DTA, distal DTA, proximal abdominal aorta, maximal DTA, and maximal abdominal aorta within 3 months after dissection were 1.3 (9.6), 12.6 (18.2), 7.6 (11.7), 5.9 (7.5), 16.7 (19.8) and 6.8 (8.9) mm/year, respectively. More than 2 years later, they were 0.2 (0.6), 1.6 (1.6), 1.2 (1.3), 0.9 (1.4), 1.7 (1.9) and 1.2 (1.7) mm/year, respectively. Factors associated with aneurysmal changes after uncomplicated ABAD included an elliptical true lumen  is a catastrophic cardiovascular condition associated with high morbidity and mortality. Acute type B aortic dissection (ABAD) is a catastrophic cardiovascular condition associated with high morbidity and mortality. However, ABAD is associated with better survival than acute type A aortic dissection. Patients with uncomplicated ABAD are mainly treated conservatively . HoweverRecently, guidelines and studies have shown the benefit of TEVAR in high-risk patients of uncomplicated ABAD , 18. EveTherefore, the objective of this study was to evaluate changes in aortic growth rate after uncomplicated ABAD and to identify factors associated with favourable results following early aortic intervention.Our institutional review committee approved this retrospective study . The need for informed consent was waived because of the retrospective nature of this study. We present this article in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology guideline checklist.Patients with uncomplicated ABAD who underwent >2 serial computed tomography (CT) imaging were studied from September 2004 to January 2020. Uncomplicated ABAD was defined as the absence of organ malperfusion and presenting within 14 days of symptom onset. Patients who underwent endovascular treatment such as TEVAR and fenestration during their initial hospitalization were excluded. Other exclusion criteria were: (i) an unclear onset, (ii) an initial aortic diameter of >55 mm, (iii) a completely thrombosed false lumen (FL) or intramural haematoma, (iv) traumatic or iatrogenic dissection, (v) ABAD confined to the abdominal aorta or (vi) ABAD combined with a congenital anatomical variation such as an aberrant subclavian artery or coarctation of aorta  reviewed CT scans using INFINITT PACS . We reviewed CT images performed on the day of admission for aortic dissection in all patients and measured the tear site, true lumen (TL) and FL conditions, and the size of the proximal entry. The aortic diameter was measured by CT at the time of admission to the emergency room, within 3 months, within 1 year, within 2 years and the most recent CT. The growth rate between each period of CT was calculated. The location of the tear site and the size of proximal entry were measured by evaluating axial, coronal, and sagittal images. If elliptical configuration of the TL was observed at any level in descending thoracic aorta (DTA), it was defined as elliptical TL. The diameter was measured at a total of 6 levels. The proximal DTA (pDTA) was measured immediately below the left subclavian artery (LSCA). The mid-DTA (mDTA) was measured at the left lower pulmonary vein level. The distal DTA (dDTA) was measured above the coeliac artery. The proximal abdominal aorta (pAA) was measured below the lowest renal artery  was used for all statistical analyses. Shapiro–Wilk test was performed to evaluate the normality of continuous variables. According to the test for normality distribution, either Student’s t-test or Mann–Whitney U-test was used for the comparison of growth rates at different time intervals. Univariable and multivariable logistic regression analyses for rapid (>5 mm/year) aortic growth rate in 2–3 years were performed. Variables that showed a P-value of <0.2 in the univariable analyses were chosen for multivariable analysis. In the multivariable analysis, backward conditional variable selection method was applied with the probability for the entry of 0.05 and the removal of 0.10.Categorical variables are expressed as numbers (%). Continuous variables are reported as mean (standard deviation) or median (interquartile range) and compared by Student's n = 77, 73.3%). Based on initial radiographic findings, 41 (39.0%) patients had a maximal aortic diameter >40 mm. Intimal tears were observed at pDTA in 67 (63.8%) patients. An elliptical TL and a patent FL were observed in 37 (35.2%) and 55 (52.4%) patients, respectively. Twenty-four (22.9%) patients had a proximal tear of larger than 10 mm. The mean follow-up duration was 35.4 (12.1–77.4) months. Additional baseline characteristics are presented in Table A total of 105 medically treated patients were enrolled in this study. All patients were Asians, including 82 (78.1%) male patients. The median age of all patients was 51 (44–63) years. The most common comorbidity was hypertension (P = 0.041). The dDTA increased rapidly to 7.6 (11.7) mm/year in the initial 3 months. It then decreased to 1.9 (3.0) mm/year at 1 year, which was statistically significant compared to the rate at 3 months (P = 0.045). At the second year, the aortic growth rate was further reduced to 1.1 (2.3) mm/year. The pAA rapidly increased to 5.9 (7.5) mm/year at the first 3 months. It then declined to 1.4 (1.9) mm/year at the first year, which was statistically significant compared to the rate at 3 months (P = 0.015). At the second year, the aortic growth rate declined further to 0.9 (1.6) mm/year , 2.9 (5.2), 2.1 (4.0), 1.2 (2.2), 3.3 (5.6) and 1.4 (2.5) mm/year, respectively. The growth rate of pDTA was low. Thus, no difference in growth rate was found during the follow-up period. In contrast, the mDTA increased rapidly to 12.6 (18.2) mm/year in the first 3 months. It then decreased to 4.3 (5.0) mm/year in the first-year follow-up. The rate gradually declined to 1.5 (4.1) mm/year at the second year, which showed a statistically significant difference compared to the first-year rate (P = 0.009) and the second interval (P = 0.037) showed statistically significant differences. The maxAA rapidly increased to 6.8 (8.9) mm/year at 3 months and then decreased to 1.5 (3.3) mm/year at 1 year, which was statistically significant compared to the rate at 3 months (P = 0.019). The aortic growth rate declined further to 1.5 (2.2) mm/year at the second year  mm/year at 3 months. It then decreased to 3.9 (3.9) mm/year at the first year. It declined eventually to 1.7 (3.2) mm/year at the second year. Both the first interval  were included. Both elliptical TL shape  and proximal entry >10 mm  were factors associated with aneurysmal dilatation after uncomplicated ABAD  the aortic growth rate after uncomplicated ABAD was not linear  and (ii) predictors of aneurysmal change after ABAD included an elliptical TL and a large proximal entry on initial CT imaging. These results need to be considered when determining early aortic intervention after uncomplicated ABAD.Uncomplicated ABAD is an aortic disease with low in-hospital mortality. However, it can lead to various changes in the downwards aorta during the follow-up period . Althouget al. [et al. [Studies reporting temporal variation in aortic growth rate are very rare. Hosn et al.  have fou [et al.  have preIn this study, we demonstrated that the aortic growth during the follow-up period of uncomplicated ABAD did not show a linear pattern . Although histological changes after acute aortic dissection have been studied, detailed patterns that change over time have not yet been reported. However, many researchers have explained that various pathological changes can affect the overall integrity of the aorta . The patTEVAR for ABAD is showing good results. In particular, the role of TEVAR for complicated ABAD or ABAD with aneurysmal change on initial CT is clear . HoweverNotably, our study showed fewer changes in the diameter of pDTA because the diameter was measured immediately below the LSCA, which is more proximal than the intimal tear. Thus, it is difficult to implicate it in the dissection. If the pDTA level was measured from the straight portion over the aortic curvature, the pDTA might show a higher growth rate than the mDTA. This finding can also be interpreted in other ways. When performing TEVAR in ABAD patients, the LSCA level used as the proximal landing zone changes little in diameter with the passage of time. Thus, the aortic diameter of the LSCA level represents a robust parameter for stent graft sizing.Results of our study suggest that factors associated with aneurysmal dilatation in the radiologic findings include an elliptical TL and a proximal large entry, which are frequently reported in many previous studies. An elliptical TL indicates increased pressurization of the FL, which induces higher radial force in the FL and causes aneurysmal dilatation , 25. A pt-test. Although this study tried to investigate the correlation between radiological characteristics and aneurysmal changes, since only the radiological variables were included and the patient clinical characteristics and history were excluded, bias may have been present in the risk factors identified for the aneurysmal dilatation. Finally, the evenness of the interval was arbitrary. We tried to find out that the aortic growth rate was very high immediately after uncomplicated ABAD by following up at the initial 3-month interval rather than the regular 1-year interval.This study has several limitations. It was a single-centre, retrospective observational study that enrolled a relatively small number of Asian patients. In addition, most CT scans were non-ECG-gated, making it difficult to accurately measure the aortic diameter in the axial view of the CT. We calculated the aortic diameter including the outer wall as the largest short-axial diameter. However, errors due to aortic tortuosity were not eliminated. We measured the diameter in only the axial view because patients arriving from local clinics underwent CTs performed via different modalities. In addition, it was technically difficult to perform measurements based on the centreline due to characteristics of aortic dissection. Instead, while reviewing serial CT imaging of each patient, we minimized the error by measuring the aortic diameter at the same level and in the same direction as in the initial CT. In addition, the fact that only 2 researchers performed all image reviews could be a limitation. Statistically, a paired test is optimal for comparing variables that are correlated with each other. However, paired tests could not be conducted because of missing values. We calculated the growth rates between 5 time points and compared the mean growth rates back and forth using the Student’s In our experience, the aortic growth rate after uncomplicated ABAD is not linear. The aortic growth rate after uncomplicated ABAD was higher at the early stage. It then decreased over time. Factors associated with aneurysmal dilatation after ABAD included an elliptical TL and a large proximal entry on initial CT imaging. These results might need to be considered when determining early aortic intervention after uncomplicated ABAD. Further investigation is needed.Conflict of interest: none declared.The data underlying this article will be shared upon reasonable request to the corresponding author.Jae Hang Lee: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Project administration; Visualization; Writing – original draft. Joon Chul Jung: Data curation; Investigation. Bongyeon Sohn: Data curation; Investigation. Hyoung Woo Chang: Formal analysis; Investigation; Methodology; Visualization. Dong Jung Kim: Conceptualization; Supervision. Jun Sung Kim: Conceptualization; Supervision. Cheong Lim: Conceptualization; Supervision. Kay-Hyun Park: Conceptualization; Supervision.Interactive CardioVascular and Thoracic Surgery thanks Luca Bertoglio, Sven Peterss, Gabriele Piffaretti, Thomas Schachner and the other, anonymous reviewer(s) for their contribution to the peer review process of this article.


Choline is a key methyl donor synthesized endogenously in mammals, and its availability is important for various biological functions. A review of the literature presents controversial results and deals with the question of whether rumen-protected choline supplemented during the transition period significantly affects cows’ health, production, and reproduction. However, most recent research shows that in dairy cattle, choline supplementation improves milk yield, composition, and fertility.n = 60) cow diet was supplemented with 10 g/day RPC from 20 days pre-calving to 20 days post-calving, and CONT (n = 60) were fed a conventional diet. BHB and P4 concentrations were measured at 5–64 DIM and 21–64 DIM, respectively, with DelPro 4.2. BHB was lower in the CHOL group at 5–64 DIM than CONT p > 0.05. The first post-calving P4 peak, p < 0.001, was determined earlier in the CHOL group, and the P4 profile during 21–64 DIM was similar, p > 0.05. The insemination rate was lower, and the interval between calvings was shorter. The first insemination time was earlier in the CHOL group, p < 0.05. Milk yield was higher in the CHOL group at 21–64 DIM, p > 0.05. The CHOL group had more fat in their milk at 31–60 DIM, p < 0.05. There were no significant differences in protein and SCC between the groups, p > 0.05. Based on our results, we concluded that the supplementation of RPC pre- and post-calving had statistically significant effects on the first peak of P4, and benefited the reproduction performances, milk yield, and milk fat during the early postpartum period.We aimed to evaluate the effects of organic herbal preparations containing rumen-protected choline (RPC) in dairy cow milk’s BHB and progesterone (P4) concentration changes, reproduction, and production performances. Cows were divided into the following two groups: The CHOL ( Increasing dairy cows’ productivity negatively impacts their health and reproduction . This teIt has been reported that 40–70% of lactating dairy cows of different breeds and milk yield levels under different management systems develop metabolic and/or infectious diseases during the postpartum period . HoweverMost health disorders occur during the late gestation and early lactation transition periods . The traSubstantial lipid mobilization from adipose tissue increases oxidative stress, impairs immunity, and is associated with higher incidences of periparturient health problems .The cow will likely experience fatty liver syndrome. The disturbance in hepatic function leads to a weakness in subsequent milk yield and is associated with poor reproductive success . The pro3)3N + CH2CH2OH], is a methyl donor. It is synthesized endogenously and is a key methyl donor in mammals; its availability is important for various biological functions [Trimethyl ethanolamine, called choline [ from 1 April 2020 to 1 November 2021, where cows were housed in a cold, loose housing system with automatic cattle drinkers, no litter, and bearings lined with rubber mats.n = 60) and experimental —according to body condition, live weight, parity, and milk yield of their previous lactation. They remained in these groups until 64 DIM. All cows were fed a TMR diet NO. 1 (Diet1) until calving and with diet NO. 2 (Diet2) post-calving until 64 DIM. The CHOL group’s Diet1 and Diet2 were supplemented with 10 g of a rumen-protected choline (RPC) source  from 20 days pre-calving to 64 days post-calving. The rations were calculated using the HYBRIMIN 2008® Fütterungs software  for dry cows (Diet1) and fresh cows (Diet2). Diet1 was formulated to meet the requirements of a 650 kg Lithuanian Black and White cow during the transition period . The ration’s chemical composition was 11.8 kg (DM) , with crude protein accounting for 1.6 kg (DM), crude fiber for 2.7 kg (DM), fiber carbohydrates for 2.3 kg (DM), and non-fiber carbohydrates for 2.2 kg (DM), and the total energy for lactation was (NEL) 6.0 MJ/kg DM. The total mixed ration consisted of corn silage 26.1%, wheat straw 14.9%, grass silage 14.9%, sugar beet pulp silage 11.2%, grain concentrate mash 14.01%, and water. Diet2 was formulated to meet the requirements of a 650 kg Lithuanian Black and White cow producing 37 kg/d of milk . The ration’s chemical composition was 24.0 kg (DM) , with crude protein accounting for 4.1 kg (DM), crude fiber for 3.4 kg (DM), fiber carbohydrates for 2.5 kg (DM), and non-fiber carbohydrates for 7.3 kg (DM), and the total energy for lactation was (NEL) 7.37 MJ/kg DM. The total mixed ration consisted of corn silage 33.9%, grass silage 20.9%, sugar beet pulp silage 17.4%, grain concentrate mash 13.0%, wheat straw 1.04%, molasses 1.7 %, and water. Feeding was conducted mechanically using a Keenan Klassik 100 divider mixer  with electronic scales.A total of 120 multiparous  healthy  Lithuanian Black and White dairy cows with body condition scores ranging from 3.75 to 4.0  and simDry cows were fed once daily at about 07:00 a.m., and cows post-calving were fed twice daily at 05:00–06:00 a.m. and p.m. according to the group diet (CONT or CHOL). Cows were milked automatically using the DeLaval milking robot  twice daily at 04:00 a.m. and 4:00 p.m.The β-hydroxybutyrate (BHB) and progesterone (P4) concentrations in cow’s milk were determined using a fully automated real-time analyzer, the Herd Navigator , combined with the milking robot. The milking robot automatically obtained a sample of a couple of milliliters of milk from each CONT and CHOL group at 5 DIM for BHB and 21 DIM for P4 determination. The subsequent milk samples were obtained according to the system’s algorithm on average every 2.2 ± 1.9 days. The analyzer measured the concentration of BHB and P4 in the milk using a biosensor and sent the BHB and P4 values to the management system DelPro 4.2 .Information on the milk yield of each cow was accumulated by the management system DelPro 4.2.  The milk composition was evaluated every 30 days (control milking), starting from 10 to 15 days post-calving. The analysis of milk fat, protein, and SCC content was performed using the infrared mid-range meter LactoScope FTIR , where the number of milk constituents was determined from the absorbed energy. The somatic cell count in milk was determined using Somascope  equipment and the principle of flow cytometry. The experimental milk was first mixed with a staining solution, after which the mixture entered the part of the device where it was illuminated with ultraviolet light, activating the fluorescent molecules and causing each stained cell to glow. A computer program registered the received signals and somatic cell count per milliliter of milk.Data on the insemination rate (the insemination times performed until cows from the group became pregnant divided by the number of pregnant cows), or the period between calving and the first insemination time, were obtained from the DelPro 4.2.  farm management platform.p ≤ 0.05.Experimental research data were analyzed using statistical software SPSS . The data were presented using descriptive statistics and normal distribution analysis methods, such as the Kolmogorov–Smirnov test. The results were produced as the mean ± standard error of the mean (M ± SE). ANOVA was used to analyze the differences between the mean values of normally distributed variables. The differences were considered significant when p > 0.05  concentration at 21–24 DIM was 45.65% higher in the CHOL group than in the CONT group. Despite noticeable differences, the difference was not statistically significant. The P4 concentration of the CHOL group was 7.63% higher than the CONT group at 21–64 DIM with  < 0.001 .p < 0.05. The interval between calvings was 4.67% shorter in the CHOL group than in the CONT group with p < 0.05. Furthermore, the first insemination time was 8.86% earlier in the CHOL group than in the CONT group of cows with p < 0.05 . Subsequently, the difference in milk yield was more noticeable between the CHOL and CONT cow groups. Milk yield for the 21–64 DIM period was 7.87% higher in the CHOL group than in the CONT group with p < 0.001  of lactation was 0.08% lower in CHOL than in the CONT group at 5–20 DIM ( < 0.001 .p > 0.05) and 0.58% more for the period of 40–55 DIM than in the CONT group (p < 0.05). The milk of the CHOL group contained less protein (0.09%) at 10–15 DIM and 0.23% more at the 40–55 DIM period than the CONT group (p > 0.05). Furthermore, milk from the CHOL group had less SCC (45.83%) at 10–15 DIM and 8.2% more at 40–55 DIM than the CONT group, with p > 0.05  . However, we detected a P4 concentration peak earlier in the post-calving period in the CHOL group than in the CONT group. In our opinion, RPC tended to accelerate the first insemination time in 7.3 days and for 19.4 days, shortening the period between calvings in the CHOL group of cows. We also observed that the insemination rate of cows was lower in the CHOL group than in the CONT group. Similar results were reported by Zenobi et al. (2018) who found that rumen-protected choline (RPC) supplemented during the transition period improved the conception rate after insemination and also conceivably affected embryonic development [Feeding RPC during the transition period led to shorter intervals from calving to first luteal activity (CLA) and better reproduction performance parameters . Our results showed that the progesterone (P4) profile during 21–64 DIM was similar in the CHOL and CONT groups , CLA is a significant marker in early lactation for traditional fertility measurements, such as pregnancy to first insemination, the number of inseminations per service period, and the interval from first to last inseminations . HoweverOur research results showed that supplementing RPC affected cows’ milk yield and composition. RPC supplementation was 7.87% higher in CHOL compared with the CONT group during 21–64 DIM and was similar to the results established by Jayaprakash . He statp > 0.05), indicating that healthy cows participated in the study.In our research, RPC supplementation increased the fat content in milk. Supplementation with RPC facilitates phospholipid synthesis, lipid absorption, and transport to the mammary gland, thus favoring milk fat synthesis ,19,20,21RPC supplementation for dairy cows from the second week before calving to the second week of post-calving did not affect the BHB concentration during the early post-partum period. Feeding cows RPC influenced their reproductive performances. We detected the first peak of P4 earlier, a shorter first insemination time, decreased insemination rate, and a shorter period between calvings when cows were fed RPC. RPC supplementation significantly increased milk yield and fat content, but no statistically significant differences were observed in milk protein and SCC at 60 DIM. Therefore, further studies are required to quantify the impact of rumen-protected choline supplementation on dairy cows’ health status and reproduction.


We evaluated the prevalence of vascular complications and associated risk factors in individuals with type 2 diabetes mellitus (T2DM) initiating second-line glucose-lowering therapy from the Middle East and Africa (MEA) cohort of the 3-year prospective DISCOVER study involving 15,992 patients in 38 countries.Baseline cross-sectional data collected from healthcare settings were used to assess micro and macrovascular complications prevalence as crude and age- and sex-standardised. The multi‐variable analysis assessed factors associated with these complications.Of 3,525 enrolled patients (mean age: 54.3 ± 10.8 years), >40% had hypertension and hyperlipidaemia. Metformin monotherapy was the first-line therapy in 56.5%, followed by metformin+sulphonylurea (20.3%). Crude and standardised prevalence of microvascular complications were 17.7% and 16.9%  and macrovascular complications were 10.7% and 8.7% . Factors significantly (p<0.05) associated with micro and macrovascular complications (odds ratios [95% CI]) were age (1.24 [1.12–1.39] and 1.58 [1.35–1.84]), male sex (1.33 [1.04‐1.70] and 1.71 [1.22–2.40]), hyperlipidaemia (1.33 [1.07-1.65] and 1.96 [1.46-2.63]) and hypertension (1.75 [1.40–2.19] and 2.84 [2.07-3.92]).A substantial burden of vascular complications with prominent risk factors in the MEA cohort calls for early preventive interventions. Diabetes has seen exponential growth over the last two decades transcending all the socioeconomic and national boundaries to become a truly global epidemic . There hIn Africa, despite the lowest Age-adjusted diabetes prevalence and the highest proportion of undiagnosed diabetes among all IDF regions, South Africa registered a prevalence of 12.7%  is associated with various micro and macrovascular complications that negatively impact the quality of life and increase morbidity and mortality and account for the majority of the social and economic disease burden –8. T2DM A comprehensive understanding of the impact of patients’ characteristics, risk factors and management patterns in terms of clinical outcomes and T2DM progression is needed to improve the quality of interventions and reduce the burden of T2DM. In Middle East and Africa (MEA) countries as in many regions, such data remain scarce , 13. ThuConsidering the paucity of data in MEA countries on the prevalence of T2DM-related vascular complications at an early stage of the disease, we report the data from the MEA cohort of the DISCOVER study on the prevalence of microvascular and macrovascular complications and associated factors in individuals with T2DM, using a standardised methodology. Data from the DISCOVER overall population has been published earlier .NCT02322762] and J‐DISCOVER in Japan [NCT02226822]). The methods and statistical analysis have been described in detail elsewhere  representing the DISCOVER-MEA cohort.Patients with T2DM, recruited from primary and specialist healthcare settings, initiating a second-line GLT after a first-line oral monotherapy or combination  therapy were enrolled in routine clinical practice. Patients were excluded if they had type 1 diabetes, were pregnant or using an injectable agent as first-line treatment. Informed consent was obtained from all the patients participating in the study at each site. The eligibility criteria are detailed in The reporting of results in the manuscript is as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist .1c], total cholesterol, high‐density lipoproteins, low-density lipoproteins), duration of T2DM, first-line GLTs (received by patients before study baseline), second-line GLTs (prescribed at study baseline) and reason(s) for change in anti-diabetic therapy were collected at initiation of second-line therapy, co-medications, medical history and presence of comorbidities (including existing diabetes-related vascular complications) , laboratory parameters (glycated haemoglobin ). Baseline HbA1c did not vary significantly across the countries (mean HbA1c range 8.3% to 9.0%). Among co‐morbidities, hypertension was reported in 43.2%  and hyperlipidaemia in 40.1%  of the patients in the overall MEA cohort. Bahrain and South Africa had a comparatively higher percentage of patients with hypertension (68.6% and 67.2%) while Kuwait (82.4%), Oman (77.4%), Bahrain (70.0%) and UAE (63.2%) had a higher percentage of patients with hyperlipidaemia compared to the overall cohort. Statins , angiotensin-converting enzyme inhibitors  and aspirin (22.4% [n=790]) were the most frequent co‐medications in the overall MEA cohort.The sociodemographic characteristics and clinical data of 3,525 patients included in the MEA cohort are presented in As first-line GLTs, more than half  of the patients received metformin monotherapy, followed by dual therapy of metformin+sulphonylurea (SU) in 20.3% (n=714). In a country-wise analysis of first-line GLT, except for Oman (29.0%) and Kuwait (21.6%), metformin monotherapy was commonly prescribed as first-line GLT (range: 40.2% to 87.1%). In Oman and Kuwait, dual therapy of metformin+SU was the most prescribed treatment (58.1% and 33.3%) as first-line GLT, respectively. Except for Egypt, metformin+SU was the second most common GLT (range: 10.0% to 58.1%). In Egypt, SU monotherapy was the second most commonly prescribed (33.2%) GLT.The crude prevalence of microvascular complications in the overall MEA cohort was 17.7%; the age- and sex-standardised prevalence was 16.9%    and 8.7% , respectively. The prevalence varied markedly across the countries in MEA  and macrovascular complications at 9.2%  that varied across the regions .This manuscript explored the crude prevalence of cardiovascular disease (CVD) in the MEA region, which is less than what has been observed in western countries as shown by global data, warranting further explanation . Of the 1c was above the target of 7.0% recommended by international (1c (8.3% [interquartile range: 7.6% to 9.4%]) values, more than 50% of patients for whom HbA1c was reported had levels above 8.0%, and >25% had a measurement higher than 9.0%. This suggests suboptimal glycaemic control and delayed treatment intensification increasing the risk of vascular complications.In line with the global data and as expected in patients who were moving to second-line therapy, mean HbAnational , 18–20 anational –23. BaseMore than 40% of patients in the MEA cohort had hyperlipidaemia and hypertension and most of them were prescribed statins and ACEis. A similar prevalence of hypertension and hyperlipidaemia was observed in cross-sectional studies from Saudi Arabia, Turkey and Jordan –27. In tThe prevalence of micro and macrovascular complications in people with T2DM has been evaluated in several studies. In the international, open-label, observational A1chieve study in more than 66,000 individuals with T2DM initiated on insulin across 28 countries from 4 continents , the overall prevalence of micro and macrovascular complications was 53.5% and 27.2%, respectively compared with 65.8% and 28.7% for micro and macrovascular complications in the Middle East subgroup . Also, t1c compared with individuals without complications .In a retrospective cohort study in the United States reporting the prevalence of micro and macrovascular complications in 135 199 patients with newly diagnosed T2DM, the prevalence of CKD was 12.3%, peripheral neuropathy was 3.8% and composite CVD was 3.3% at diagnosis . A study1c, history of hyperlipidaemia and hypertension but the association was only significant with higher age, male sex, current/ex-smoking status, and history of hyperlipidaemia and hypertension (p<0.05). Micro and macrovascular complications were positively and significantly associated with the same risk factors but the ORs were higher for macrovascular complications. Additionally, we found that BMI and HbA1c were not significantly associated with either micro and macrovascular complications similar to that reported for the global DISCOVER study population macrovascular analysis but contrasts with microvascular one where HbA1c was found to be significantly associated .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.


This study investigated the clinical outcome of XEN45® implantation after a failed TE, with follow-up data of up to 30 months. Materials and Methods: In this paper, we present a retrospective review of patients undergoing XEN45® implantation after a failed TE at the University Eye Hospital Bonn, Germany, from 2012 to 2020. Results: In total, 14 eyes from 14 patients were included. The mean follow-up time was 20.4 months. The mean time duration between the failed TE and XEN45® implantation was 110 months. The mean intraocular pressure (IOP) decreased from 17.93 mmHg to 12.08 mmHg after one year. This value increased again to 17.63 mmHg at 24 months and 16.00 mmHg at 30 months. The number of glaucoma medications decreased from 3.2 to 0.71, 2.0, and 2.71 at 12, 24, and 30 months, respectively. Conclusions: XEN45® stent implantation after a failed TE did not lead to an effective long-term decrease in IOP and glaucoma medications in many patients in our cohort. Nevertheless, there were cases without the development of a failure event and complications, and others in whom further, more invasive surgery was delayed. XEN45® implantation in some failed trabeculectomy cases may, therefore, be a good option, especially in older patients with multiple comorbidities. Background: The implantation of a collagen gel micro-stent (XEN45 Thisstration ,14.® gel stent implantation as a therapy modality after a failed trabeculectomy, showing that it can be an effective option for certain patients [In cases with failed trabeculectomy, glaucoma drainage devices or revision surgery of the failed trabeculectomy site can lead to the further lowering of IOP ,16,17. Hpatients ,20,21. H® implantation without combined cataract surgery. Only those patients who had received a XEN45® implantation after a failed trabeculectomy and with complete follow-up data over 12 months were included for further analysis. Patients who had undergone surgery without an earlier trabeculectomy and those with incomplete follow-up data were subsequently excluded. All the medical records of patients who underwent XEN45® implantation for chronic open-angle glaucoma, pseudo-exfoliation glaucoma, and neovascular glaucoma at the Department of Ophthalmology at the University Hospital of Bonn, Germany, from 2012 until 2020 were reviewed retrospectively. All patients received standalone XEN45All patients underwent a full ophthalmic examination upon presentation, including an assessment of best-corrected visual acuity (BCVA) using Snellen charts , IOP measurement via Goldmann applanation tonometry, slit-lamp biomicroscopy, fundus biomicroscopy, and a visual field test, using the Humphrey 24-2  for a visual field test. The documented data included gender, age, glaucoma type, BCVA, preoperative clinical features , and detailed follow-up information regarding BCVA, IOP, visual fields, complications, and postoperative glaucoma medication. Patients were censored for further analyses from the point of any additional glaucoma surgery. Patients received an additional glaucoma operation if the IOP was insufficiently controlled after XEN45® implantation, despite maximal therapy and visual field progression.® implantation surgery was defined as an IOP either below 6 mmHg or over 21 mmHg, measured over two visits paid at least 3 months after surgery; the need for additional glaucoma surgery was established for persistently raised IOP and/or in cases resulting in the loss of light perception. All analyses were conducted on a de-identified data set. A waiver from the local Ethics Committee was granted, due to the retrospective nature of the study. The study protocol conformed to the ethical guidelines of the 2000 Declaration of Helsinki, as reflected in the a priori approval granted by the institution’s Human Research Committee. The failure of XEN45Statistical analysis was performed with SPSS Statistics version 27.0.0 . Time-dependent survival probabilities were estimated with the Kaplan–Meier method.In total, 14 patients were included in this study. The mean age was 71 years. After exclusions, 5 women (35.7%) and 9 men (64.3%) were included. The mean BCVA, measured preoperatively, was 0.47 logMAR. Thirteen patients (92.9%) were pseudophakic. Further characteristics of our patient cohort are described in The mean follow-up time was 20.4 months, with a maximum follow-up time of 34 months (12–34 months). Eight patients (57.1%) had a diagnosis of primary open-angle glaucoma (POAG), while 5 patients (35.7%) had pseudo-exfoliative (PEX) glaucoma. The preoperative mean IOP was 17.93 mmHg, with a maximum of 25 mmHg and a minimum of 11 mmHg. The mean maximum IOP obtained from each patient’s medical history was 22.27 mmHg (16–35). Preoperatively, patients were on a mean number of 3.2 topical glaucoma medications. The majority of patients  were taking 4 pressure-lowering agents. Almost all patients  were not on additional systemic acetazolamide therapy. The mean vertical cup-to-disc ratio was 0.78. The mean deviation (MD), measured preoperatively with a Humphrey visual field analysis (24-2), was −13.75 dB and the pattern standard deviation (PSD) was 8.6 dB.® implantation surgery was 110 months, with a maximum of 270 months and a minimum of 36 months. During the postoperative course, 3 patients (21.4%) underwent an additional glaucoma procedure. Of these 3 patients, one patient underwent trans-scleral cyclo-diode laser treatment, one patient underwent trabectome surgery, and one patient underwent PreserFlo® Microshunt implantation. The mean time period between XEN45® gel implantation and additional glaucoma surgery was 10.33 months .The mean duration between the operative date of the failed trabeculectomy and the XEN45Of all 14 patients, 4 patients (28.6%) developed a failure event .Failure criteria were applied, as explained above. As aforementioned, 3 patients of the 4 (75.0%) failed due to additional glaucoma surgery, and 1 patient (25%) failed due to persistent high IOP levels over 21 mmHg, recorded over two visits .Five patients (35.7%) developed complications during the postoperative course; two of these had more than one complication. One patient experienced a hyphema immediately after surgery and one patient exhibited corneal oedema. These complications eventually resolved without the need for additional interventions. One patient showed a numerical hypotony during the first days after surgery .® implant, with the repeated application of Mitomycin C; one patient underwent partial removal of the XEN45® implant (Two patients underwent revision surgery of the XEN45 implant . Both pan = 14), the IOP decreased to a mean IOP of 9.86 mmHg, with an IOP drop of 40% in comparison to the preoperative IOP. The number of IOP-lowering drops was considerably lower than before surgery (0.29). One week after surgery, the results were comparable to the first day after surgery (n = 14). The IOP was 10.63 mmHg and the mean number of pressure-lowering eye drops was 0.5. During both time periods, the BCVA had decreased.On the first day after surgery (n = 14), the IOP was 15.41 mmHg; 3 months after surgery, it was 12.67 mmHg (n = 14), and six months after surgery, it was 12.08 mmHg (n = 14). One year after surgery, the follow-up data were complete for all 14 patients and showed a mean IOP of 12.08 mmHg. In comparison to the preoperative value, the mean IOP had decreased by 4 mmHg. However, the mean IOP had further increased to 17.63 mmHg at 18 months (n = 9), then changed to 14.25 mmHg at 24 months (n = 7), and to 16.00 mmHg at 30 months after surgery (n = 7)  . When only the 7 patients with a follow-up time of 24 months were included in the analysis, the mean preoperative IOP was 19.25 mmHg at month 6, 13.63 mmHg at month 12, 17.63 mmHg at month 24, and 16 mmHg at month 30. n = 14), 1.0 at 3 months (n = 14), 0.75 at 6 months (n = 14), and 0.71 at one year after surgery (n = 14). Compared with the preoperative amount of 3.2 drops, the number was considerably lower at one year after surgery (The amount of pressure-lowering eye drops was 1.0 at one month ( surgery .n = 7) and 2.71 drops at 30 months after surgery (n = 7). Nevertheless, the amount increased again, with a mean of 2.0 drops at two years (n = 14), 0.69 logMAR after 6 months (n = 14), 0.72 logMAR after 12 months (n = 14), 0.82 logMAR after 24 months (n = 7), and 0.84 logMAR 30 months (n = 7) after surgery.Overall, the BCVA showed some deterioration during the time period after surgery, from 0.52 logMAR, preoperatively, to 0.84 logMAR one week after surgery (n = 7) and 0.81 (0.5–0.99) after 30 months (n = 7). The mean preoperative cup-to-disc-ratio (CDR) was 0.78 (0.5–0.99) and showed a slight deterioration during the postoperative course, with 0.81 (0.5–0.99) after 24 months (n = 14), −16.92 dB at one year (n = 13), −15.46 dB at two years after surgery (n = 6) and −16.43 dB at 30 months (n = 6). In comparison to a preoperative value of −13.75 dB, these results showed a slight progression in the visual field tests. However, when comparing the pattern standard deviation with a preoperative value of 8.6 dB to 9.5 dB at 6 months (n = 14), 7.2 dB at 1 year (n = 13), 9.9 dB at 2 years (n = 6) and 10.1 dB at 30 months (n = 6), the visual field defects showed only a discrete progression. The visual field test results showed a mean deviation of −15.75 dB at six months . Data were complete for every patient of our cohort after one year, were still complete for half of the patients after 24 months, and complete for 7 patients after 30 months. The other half were lost to follow-up or were censored due to failure events. Karimi and colleagues performed a retrospective study with 17 patients in 2018, but they only included follow-up data for 12 months [To the best of our knowledge, our study shows the longest periods of follow-up results available until now for XEN452 months . Bormann2 months . We included 14 patients with a preoperative IOP of 17.93 mmHg, with a range from 11 mmHg to 25 mmHg. One patient had a preoperative IOP of 11 mmHg, which is considered quite low for listing this patient for surgery. However, this patient had been prescribed an intake of acetazolamide and the maximum amount of pressure-lowering medication, with an even lower target IOP.® stent implantation. Düzgun et al. described 14 patients who received XEN45® in the inferonasal quadrant, who showed an IOP-reduction of 49.3% (from 24.14 mmHg to 12.23 mmHg) and a reduction in eyedrops from 3.71 to 1.31, on average [® reduced the IOP from 21.5 to 13.6 mmHg and the number of pressure-lowering medications from 2.8 to 1.0 after 12 months [® reduced the IOP from 23.5 to 18.0 at 12 months, postoperatively [® stent implantation after a failed trabeculectomy, and concluded that XEN45® could be a good method to overcome failed trabeculectomies with minimally invasive surgery. In our cohort, the IOP was lowered to an IOP of 12.08 mmHg on average (preoperative measurement: 17.93 mmHg) and the usage of pressure-lowering agents decreased to a mean of 0.71 (preoperative measurement: 3.2 drops). After a time interval of one year, in comparison with our study, the aforementioned studies reported effective IOP-lowering after XEN45 average . Karimi 2 months . Bormannratively . All the® implantation after a failed trabeculectomy. Karimi and colleagues even conclude in their list of study limitations that a follow-up beyond 12 months would have been better to evaluate the procedure’s true efficacy after a failed TE. The above-referenced studies did not report further outcomes from other time points. To the best of our knowledge, there are no other studies presenting data on 2-year results for XEN45n = 9) and month 24 (n = 7) might be due to the exclusion of one patient who had higher IOP values and was subsequently excluded from analysis because of a failure event, while the other patient with rather high IOP values did not have further follow-up appointments. However, it must be taken into account that follow-up data at 24 and 30 months after surgery were not available for every patient and that the results can be affected by selection bias. To rule this out, we compared the IOP when only including those seven patients with an available follow-up time of 24 months . This subgroup analysis showed that these patients had a higher preoperative IOP than the average group and, thus, the IOP remained lower at month 24 than preoperatively, but was still considerably higher than after a year. The long-term follow-up data included in our study shows that XEN45® stent implantation first leads to an IOP reduction during the first year, with an increasing IOP during the second year. This is most probably due to fibrosis formation around the subconjunctival portion of the stent. In our study, we were able to maintain a connection with half of our patients for follow-up data after 30 months. The outcome after two years and 30 months showed that, unfortunately, the IOP-lowering and drug-reducing effect decreased, and, in some patients, had even reached a similar level as preoperatively. The mean IOP increased from 12.08 mmHg at month 12 to 17.63 mmHg at month 18, 14.25 mmHg at month 24, and 16.00 mmHg at month 30 after surgery. The IOP drop between month 18 , where a tube drains into the untouched post-equatorial subconjunctival space, is considered by many to be the preferred therapy option after a failed TE, especially if post-TE interventions, such as bleb needling and/or repeated antimetabolite application, have been unsuccessful in restoring bleb function. However, tube surgeries can also pose certain risks, which a XEN45® stent avoids to a significant degree. A GDD procedure is usually more complex and time-consuming and will more often result in major complications, especially with regard to persistent postoperative hypotony, corneal endothelial cell loss, and transconjunctival erosions. In addition, general anesthesia is more often necessary for GDD than it is for XEN45®. Since one of the main reasons for failure in TE is bleb fibrosis, and since the XEN45® stent implantation is a safe procedure with mostly minor complications. In our study, 5 patients (35.7%) developed complications; however, most of these were resolved without the need for additional interventions. One patient (7.1%) had a hyphema immediately after surgery, one patient (7.1%) developed numerical hypotony, and one patient (7.1%) exhibited corneal oedema, all of these complications resolving themselves without further interventions. Bormann and colleagues reported that 4 eyes (13%) developed choroidal detachment, due to postoperative hypotony, and 4 eyes (13%) developed a subconjunctival hemorrhage. Düzgün and colleagues reported that 5 eyes (35.7%) developed intracameral hemorrhage and 3 eyes (21.4%) developed postoperative numerical hypotony [® stent implantation is a safe procedure with a small risk of major complications.In concordance with the other studies described earlier, XEN45d 3 eyes .4% develhypotony  was the ® stent implantation may quite often be followed by small postoperative interventions and revision procedures to maintain its IOP-lowering effect. In our study, two patients (14.2%) had to undergo revision surgery of the implant with the repeated administration of Mitomycin C, one patient (7.1%) underwent needling, and one patient (7.1%) underwent a partial removal of the XEN45® implant. Bormann and colleagues reported similar results, with 10% needing an open revision of the conjunctiva, while 9 eyes (29%) received postoperative needling. Düzgün and colleagues reported that six eyes (42.8%) required postoperative bleb needling during the postoperative course. Karimi et al. reported that postoperative bleb intervention was performed in 9 eyes (52.9%), with a mean of 2.4 postoperative bleb needling/injections. Most patients required one of these interventions after one month. However, XEN45® stent implantation should still be considered in selected cases after a failed trabeculectomy, especially in older people with multiple comorbidities, as it offers a less invasive and quicker approach to lowering IOP for a period of time, albeit with the risk of an increase during the postoperative course. Additionally, failed XEN45® rescue surgery does not preclude GDD surgery in the future, which continues to be a treatment option later in due course. This relative lack of risk is why XEN45To the best of our knowledge, our study is the only one that includes data on visual field progression. Our 2-year results showed a slight progression of the mean deviation. The visual field test results showed a mean deviation of −13.75 dB, preoperatively, and −15.46 dB at two years after surgery. The pattern standard deviation showed a similar development from 8.6 dB, preoperatively, to 9.9 dB at 2 years. One must consider that these results are partially biased due to the selection bias inherent in the retrospective nature of this study. On top of that, in the German healthcare system, patients are usually referred to tertiary care centers in the case of insufficient pressure control or the progression of their visual fields, whereas adequately controlled patients are followed up by their respective local ophthalmologists. ® implantation after a failed TE. In these patients, after another rescue operation is performed, an ophthalmologist might feel safer about visual fields and IOP control and may be rather conservative toward more extensive surgeries in cases where the XEN45® fails as well. Eventually, ineffective treatment with XEN45® might impede or delay other, more appropriate, treatment options in the longer term. In addition to that, patients might be hesitant to have another operation since they have only just been operated upon and would not be able to comprehend the relative implications of less and more invasive surgery. It is therefore imperative that after a failed trabeculectomy, one must consider which patients might truly benefit from XEN45® stent implantation. It seems that younger patients with a high risk of scarring might benefit more from alternative procedures, such as GDD surgery.The slight progression in visual field results shows that there might be another downside to performing a XEN45


Population studies reporting contemporary long-term outcomes following catheter ablation of atrial fibrillation (AF) are sparse.We evaluated long-term clinical outcomes following AF ablation and examined variation in outcomes by age, sex, and the presence of heart failure.We identified 30 601 unique patients  undergoing AF ablation from 2008 to 2017 in Australia and New Zealand using nationwide hospitalization data. The primary outcomes were all-cause mortality and rehospitalizations for AF or flutter, repeat AF ablation, and cardioversion. Secondary outcomes were rehospitalizations for other cardiovascular events. During 124 858.7 person-years of follow-up, 1900 patients died (incidence rate 1.5/100 person-years) with a survival probability of 93.0%  92.6–93.4%) by 5 years and 84.0% (95% CI 82.4–85.5%) by 10 years. Rehospitalizations for AF or flutter (13.3/100 person-years), repeat ablation (5.9/100 person-years), and cardioversion (4.5/100 person-years) were common, with respective cumulative incidence of 49.4% (95% CI 48.4–50.4%), 28.1% (95% CI 27.2–29.0%), and 24.4% (95% CI 21.5–27.5%) at 10 years post-ablation. Rehospitalizations for stroke (0.7/100 person-years), heart failure (1.1/100 person-years), acute myocardial infarction (0.4/100 person-years), syncope (0.6/100 person-years), other arrhythmias (2.5/100 person-years), and new cardiac device implantation (2.0/100 person-years) occurred less frequently. Elderly patients and those with comorbid heart failure had worse survival but were less likely to undergo repeat ablation, while long-term outcomes were comparable between the sexes.Patients undergoing AF ablations had good long-term survival, a low incidence of rehospitalizations for stroke or heart failure, and about half remained free of rehospitalizations for AF or flutter, including for repeat AF ablation, or cardioversion.  Furthermore, while the frequently used definition of arrhythmia occurrence (AF lasting >30 s)10 is useful in clinical trial settings, less is known about the incidence of clinically meaningful episodes such as those warranting hospitalization or requiring repeat ablation or cardioversion. Moreover, data are lacking about the risk of other equally important cardiovascular outcomes such as mortality, stroke, and heart failure, which is crucial for patients and clinicians seeking to better understand long-term outcomes of AF ablation. Population studies can provide unbiased estimates of these long-term outcomes, yet existing literature is sparse and limited by short follow-up time (up to 1 year)11–13 or a focus on specific populations.14–16Although the benefits of catheter ablation in maintaining sinus rhythm have been well established in clinical trials, long-term clinical sequelae of patients undergoing AF ablation in actual clinical practice are less well known. Published studies mostly report arrhythmia-free survival rate and are often derived from selected populations and experienced ablation centres,7Accordingly, we used population-wide data to examine long-term outcomes of patients undergoing AF ablation in Australia and New Zealand (ANZ) from 2008 to 2017. Specifically, we evaluated the longitudinal risk of all-cause mortality, rehospitalizations for AF or flutter, repeat AF ablation, cardioversion, and other cardiovascular events, including hospitalizations for stroke or transient ischaemic attack (TIA) and heart failure. We also examined how the primary outcomes varied by age, sex, and the presence of comorbid heart failure as this subgroup of AF patients has been shown to experience survival benefits with catheter ablation compared with medical therapy.18We used hospitalization data from all public and most (80%) private hospitals recorded in the Admitted Patient Collection (APC) from each state and territory in Australia and the equivalent New Zealand National Minimum Dataset . Data were missing from private hospitals in New Zealand and the Australian states of South Australia, Tasmania, and Northern Territory, whose total population accounted for <10% of the total Australian population. A standard set of variables is recorded for each admission (both inpatient and outpatient visits), including patient demographic characteristics, the primary diagnosis and up to 50 secondary diagnoses, all procedures performed, and the patient's status at discharge. In both countries, diagnoses are coded using the International Classification of Diseases, 10th Revision, Australian Modification (ICD-10-AM), and procedures were coded using the Australian Classification of Health Interventions (ACHI). Accuracy of diagnosis and procedure coding is reported to exceed 85% when compared with medical records.19 In New Zealand, all patient records are linked nationally using a unique National Health Index number, and all deaths are recorded in the National Health Index Sociodemographic Profile. These linkages allowed the capture of rehospitalizations to any hospital within each region and all deaths occurring in hospital or in the community.In Australia, each encounter was linked with subsequent records within the APC and to each region's Birth, Death, and Marriages Registry by using probabilistic matching using multiple patient identifiers with reported accuracy exceeding 99%.21 In brief, we included patients aged ≥18 years hospitalized with a primary diagnosis of AF and a procedure code for catheter ablation from 2008 to 2017 and excluded those who (1) had secondary diagnoses of other arrhythmias to ensure that the ablation was solely for AF; (2) had a previous or current cardiac device implantation; (3) had open  ablation; and (4) were discharged against medical advice .The use of administrative data to identify patients undergoing AF ablations has been described previously.The primary outcomes were (1) all-cause mortality and (2) rehospitalizations for atrial arrhythmias (AF or flutter), repeat AF ablation, and cardioversion. Secondary outcomes included relevant cardiovascular events, including hospitalizations for stroke or TIA, heart failure, acute myocardial infarction, syncope, arrhythmias other than AF or flutter , and new cardiac device (pacemaker or defibrillator) implantation  from hospitalizations in the previous 12 months into 180 meaningful clinical conditions.23We presented data as frequencies and percentages for categorical variables and mean ± standard deviation (SD) or median and interquartile range (IQR) for continuous variables. Differences between groups were evaluated using 24To estimate the incidence rate, which reflects the number of new events that occurred in a given period, we divided the number of events by the patient time at risk and reported results as the number of events per 100 person-years (PY). Patients were considered at risk until they died, experienced a non-fatal outcome, or survived until the end of the study period (1 January 2018). We used the Kaplan–Meier method to estimate the survival probability and reported results as percentages with the respective 95% confidence interval (CI). For non-fatal outcomes, we estimated the cumulative incidence, which reflects the proportion of patients experiencing the event over a given period by using Fine and Gray's method of competing risk survival analysis (subdistribution hazard) with death being the competing event.25 Results are reported as hazard ratio (HR) for mortality or subdistribution HR (sHR) for non-fatal outcomes with the corresponding 95% CI. Candidate variables considered for these models included patient demographic characteristics , procedural characteristics , and various cardiovascular and non-cardiovascular comorbidities that may be associated with long-term outcomes.To examine variation in outcomes by age, sex, and comorbid heart failure, we used Cox regression survival analysis to adjust for baseline differences in patient and procedural characteristics. Simple Cox regression analysis was used with the outcome of death, while for non-fatal outcomes, separate competing risk models using Fine and Gray's method were developed with death being the competing event.P-value < 0.05 was considered statistically significant. This study was approved by the respective Human Research Ethics Committees of each state and territory in Australia. Data from New Zealand were obtained under a data user agreement with the New Zealand Ministry of Health. A waiver of informed consent was provided for the use of deidentified data.All analyses were performed using Stata version 16.0  and a two-tailed Figure 1).From 2008 to 2017, 45 398 patients were hospitalized with a primary diagnosis of AF and a procedure code for catheter ablation, of whom 30 601 unique patients met selection criteria and were included in the final study cohort (Table 1). The median length of stay was 1.0 day (IQR 1.0–2.0 days) and 94.0% of AF ablations were performed during an elective (planned) hospitalization. Nearly half of the study cohort (49.1%) had been hospitalized with a primary diagnosis of AF or flutter in the previous year, but rates of comorbidities were generally low, with hypertension (13.4%) and diabetes (10.1%) being the most common cardiac and non-cardiac comorbidities, respectively. The median estimated CHA2DS2-VASc score  and female sex and 2 points each are given for age ≥75 years old and history of stroke [S]) was 1 (IQR 0–2) with 90.1% with a score ≤2.The mean age was 62.7 (±11.8) years with 46.1% aged ≥65 years and the cohort was predominantly (70.0%) male (2DS2-VASc score (median score of 2 vs. 1) .During 124 858.7 person-years of follow-up , 1900 patients died. Compared with those who survived, deceased patients were older (72.4 vs. 62.0 years), less likely to have an elective index hospitalization (87.7% vs. 94.4%), and had a higher frequency of comorbidities such as hypertension (30.5% vs. 12.3%), heart failure (28.9% vs. 9.0%), coronary artery disease (23.0% vs. 10.0%), diabetes (16.9% vs. 9.7%), and a higher CHAA total of 30 593 patients survived the index hospitalizations, among whom 11 114 were rehospitalized for AF or flutter during follow-up. Rehospitalized patients were younger (61.5 vs. 63.3 years), had higher rate of hypertension (14.2% vs. 12.9%), and were more likely to be hospitalized for AF or flutter in the previous year (55.5% vs. 45.5%) compared with those not rehospitalized.Table 2 and Figure 2), which increased from 1.2/100 PY in the first year to 1.5/100 PY in 1–5 years and reached 2.0/100 PY at 5–10 years after the index ablation. This corresponded to a survival probability of 98.8% (95% CI 98.6–98.9%) at 1 year, 93.0% (95% CI 92.6–93.4%) at 5 years, and 84.0% (95% CI 82.4–85.5%) at 10-year, respectively.The overall incidence rate of all-cause death was 1.5/100 PY  or elective (planned) rehospitalization for AF or flutter (incidence rate 13.3/100 PY). The incidence rate peaked during the first year (29.0/100 PY) and rapidly declined to 7.8/100 PY and 3.9/100 PY at 1–5 years and 5–10 years post-ablation, respectively. The cumulative incidence of rehospitalizations for atrial arrhythmias was 23.8% (95% CI 23.4–24.3%) at 1-year, and 49.4% (95% CI 48.4–50.4%) at 10 years. Of these 11 114 patients, 5148 (46.3%) had an acute (unplanned) admission for AF or flutter with an overall incidence rate of 4.8/100 PY and a cumulative incidence of 24.8% (95% CI 24.0–25.7%).Among the 11 114 patients rehospitalized for AF or flutter, a subset of 6001 patients underwent repeat AF ablation (incidence rate 5.9/100 PY) and 4811 patients received cardioversion (incidence rate 4.5/100 PY). The incidence rate for repeat ablation was highest in the first year (12.2/100 PY), and then decreased to 1.7/100 PY in years 5–10 post ablation. The 10-year cumulative incidence was 28.1%, (95% CI 27.2–29.0%). Similarly, there was a rapid decline in the incidence rate of cardioversion for AF or flutter from 10.6/100 PY in the first year to 1.6/100 PY in years 5–10 post-ablation with an overall cumulative incidence of 24.4% (95% CI 21.5–27.5%).Overall, the incidence rates of other cardiovascular events were low. Specifically, rehospitalizations for stroke or TIA occurred at an incidence rate of 0.7/100 PY with a cumulative incidence of 6.6% (95% CI 5.8–7.5%). Similarly, the incidence rate for heart failure (1.1/100 PY) and acute myocardial infarction (0.4/100 PY) was low with a cumulative incidence of 8.5% (95% CI 7.9–9.2%) and 3.7% (95% CI 3.3–4.2%), respectively. Rehospitalizations for syncope occurred with an incidence rate of 0.6/100 PY with a cumulative incidence of 4.3% (95% CI 4.0–4.7%). The estimates for rehospitalizations for arrythmias other than AF or flutter were 2.5/100 PY and 15.9% (95% CI 15.0–16.7%) respectively. A total of 14.5% (13.6–15.3%) of patients received either a pacemaker or defibrillator (incidence rate of 2.0/100 PY) during the 10-year period. The cumulative incidence was higher among patients with comorbid heart failure  compared with those without .Figure 3A). Long term cumulative incidence of rehospitalizations for AF or flutter was lower among patients ≥80 years but was comparable between subgroups regardless of sex or the presence of heart failure . Similarly, cumulative incidence of repeat ablation was lowest in the oldest age group and comparable between sex but was lower in patients with comorbid heart failure compared with those without heart failure .The unadjusted analysis showed survival probability declined in elderly patients and those with comorbid heart failure but was comparable between sexes  while older age  and heart failure  was associated with worse long-term survival Figure S1We found that patients undergoing AF ablations in ANZ had a good long-term clinical outcome with a high survival probability and a low incidence of clinical sequelae of AF such as rehospitalizations for stroke or TIA, heart failure, and acute myocardial infarction. Furthermore, about half of the patients did not experience rehospitalization for AF or flutter, including for repeat AF ablation or cardioversion. Collectively, these findings suggest a good prognosis after AF ablation but also suggest the need for additional measures to reduce the burden of AF as nearly 50% of patients required hospitalization for AF or flutter in the 10 years post-ablation.11–13 while long-term outcome data mostly come from Asian countries15 or selected populations such as those who had cardioversion before ablation.16 Our study provided long-term outcomes from an unselected, contemporary cohort in ANZ, irrespective of age or payer. Our population was older than that in Korea and Taiwan (mean age of 51–57 years)15 but comparable with Denmark (mean age 65.5 years)16 and North America (60.0–65.3 years).11–13 Despite these differences, the incidence rate of death was consistent among studies (1.1/100 PY)14–16 but nearly double what is reported in large, multicentre clinical trials such as the Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial (0.63/100 PY).6 Similarly, rates of rehospitalizations for stroke or TIA (0.5–0.7/100 patient-years)14–16 and heart failure (0.7–1.2/100 patient-years)14–16 were consistent among population studies but higher than those reported in the CABANA trial (0.01/100 PY for disabling stroke). Collectively, patients undergoing AF ablation in clinical practice appear to have a relatively low incidence of death and hospitalizations for stroke or heart failure, although the risks are greater than those reported in clinical trials.Population studies play an important role in providing outcome data in clinical practice but existing studies primarily focus on short-term outcomes, typically up to 1 year post-ablation,14–16 Although the definition of AF recurrence as an episode lasting >30 s is commonly used in clinical trials and recommended by management guidelines,10 measuring events that require hospital admission might better reflect the direct burden these patients face. Indeed, Terricabras and colleagues have shown that regardless of AF recurrence status, catheter ablation significantly reduces the AF burden and improves quality of life, suggesting that AF burden might be a more relevant outcome measure for patients undergoing AF ablation.26 Encouragingly, we found that just over 50% of patients were free of hospital admission for AF or flutter at 10 years post-ablation, and the incidence during the first year was only 23.8%, significantly lower than the 49.1% rate in the year preceding the ablation. Given the near 50% incidence of arrhythmia recurrence (defined as AF >30 s)10 at four years post-ablation reported in the CABANA trial,6 our finding  suggests that 80% of these recurrences are likely severe enough to warrant rehospitalization. We also found that 28.1% of our patients required at least one repeat ablation, which is lower than the cumulative incidence (57.6%) reported in another population study.16 Nevertheless, the incidence rate of repeat AF ablation in our cohort was more than double that of the CABANA trial (5.9 vs. 2.6/100 patient-years),8 suggesting that in clinical practice, patients may require more frequent ablation to achieve outcomes comparable with the trial setting.We also extend the literature by reporting the longitudinal risk of hospitalization for recurrent AF or flutter and the need for repeat intervention-outcomes of critical importance that are frequently sought by patients and clinicians but rarely reported by other population studies.27 with the Catheter Ablation versus Standard Conventional Therapy in Patients with Left Ventricular Dysfunction and Atrial Fibrillation (CASTLE-AF) trial of AF ablation in those with severe heart failure (ejection fraction ≤35%) reporting a nearly 50% lower hazard of death compared with medical therapy.7 More importantly, this trial had a higher incidence of repeat ablation than that in our study (24.5% at 3.15 years vs. 14.8% at 3 years).7 This raises the possibility that AF ablation may be underutilized in patients with heart failure who might benefit most from the procedure.Another important observation is a comparable adjusted likelihood of repeat ablation in patients with heart failure despite the higher mortality risk in this subgroup. The literature has consistently shown better outcomes in heart failure patients undergoing AF ablations28 reducing alcohol consumption,29 and optimal management of AF risk factors like comorbid hypertension, diabetes, and sleep apnoea.30 Systematic implementation of these strategies may further improve ablation outcomes, decrease the disease burden, and reduce the need of hospital admission or repeat procedures.Our findings provide important prognostic information for patients and clinicians who seek to be better informed about the long-term clinical outcomes of ablation. These data are reassuring as the incidence rates of untoward outcomes such as death, stroke or TIA, heart failure or acute myocardial infarction after ablation were relatively low. Nevertheless, nearly 50% of patients required hospitalization for AF or flutter and repeat ablation, suggesting that additional measures are required to minimize the AF burden. There are several strategies proven to minimize AF recurrence and improve ablation outcomes such as weight loss,18 linkages of health records,19 and identification of AF ablation in administrative data.22 Although the algorithm to identify AF ablation in administrative data may not capture all procedures as the sensitivity is not 100%, this approach has 100% specificity and has been widely used by other studies using hospitalization data.32 Second, we could not estimate the rate of atrial arrhythmia recurrence  as not all recurrences required hospital admission. Visits to the emergency department due to AF or flutter or other cardiovascular diseases after ablation that did not lead to hospitalization were also not counted. Instead, we focused on AF or flutter hospitalizations and other events that required hospital admission—events that are most concerning for patients and clinicians and have the greatest impact on health care resources. Third, patients undergoing AF ablation in Australia and New Zealand were relatively young and had low rates of comorbidities and therefore, our results may not reflect the outcomes of AF ablations in older and sicker patients. Fourth, this study did not seek to compare outcomes of patients undergoing ablation with those of patients who did not as many AF patients may present to general practitioners , while all AF ablations are performed in-hospital. Fifth, the inherent differences in study design and patient selection criteria must be considered when comparing our results with those in clinical trials.7 Nevertheless, such a comparison was helpful to better understand the outcomes of AF ablation in clinical practice. Finally, several variables that may influence long-term outcomes were not collected in these data sets and were therefore not adjusted for, such as type of AF, type of ablation energy or lesions performed, operator experience, cardiac function, and medications used.Several limitations should be considered when interpreting our results. First, we used routinely collected administrative data that are generally less granular than those collected specifically for research purposes. However, validation studies have shown good accuracy of coded data,Patients undergoing catheter ablation of atrial fibrillation have a good long-term prognosis with 84.0% surviving by 10 years and relatively low incidence of sequelae such as stroke and heart failure. Furthermore, about half of the patients remained free of rehospitalizations for AF or flutter, repeat ablation, or cardioversion. Nevertheless, additional measures such as weight loss, alcohol abstinence, and better management of comorbidities are necessary to reduce the residual burden of AF post-ablation.qcac024_Supplemental_FileClick here for additional data file.


Juvenile idiopathic arthritis (JIA) is chronic inflammatory arthritis of childhood that may result in persistent and disabling foot impairments. Foot disorders are common in JIA with a prevalence estimated at over 90%. Many factors can worsen foot disorders in these patients. The influence of weight on foot disorders is poorly studied.To examine associations between weight and foot disorders in patients with JIA.Patients with a diagnosis of JIA, based on the International League of Associations for Rheumatology (ILAR) criteria were included. Age, gender, weight, characteristics of the disease and of foot pain were noted. A specialized podiatric examination was performed.n = 14). The mean age of disease onset was 8.5 ± 3.9 [3–15]. Only one patient had a triggering factor (elbow fracture). The most common type of JIA was oligoarthritis in 12 cases, then enthesitis-related in 8 cases, polyarthritis without rheumatoid factor in 3 cases, polyarthritis with positive rheumatoid factor in 1 case, psoriatic arthritis in 3 cases, systemic arthritis in 1 case and undifferentiated arthritis in 4 cases.Thirty-two patients were included. The mean age was 12.2 ± 2.9 [5–18]. Forty-three percent of the patients were boys (n = 9) of the children had a normal weight for their age, 41% (n = 13) of them had a low weight for their age and 31% (n = 10) of them had overweight. Ten patients had foot pain: hindfoot pain in 5 patients, midfoot pain in 3 patients, and forefoot pain in 2 patients. Foot deformities were found in 78.1% of the patients (n = 27): flat foot in 39% (n = 13) of the patients and pes cavus in 39% (n = 13).The mean weight was 43.5 kg [17–98]. Only 28%  or hindfoot pain (p = 0.08). However, overweight was associated with a forefoot (p = 0.01) and midfoot (p = 0.01) pain. Overweight was not associated with foot deformities (p = 0.1).There was no association between overweight and foot pain (This study showed that weight is associated with foot pain especially forefoot and midfoot pain. A healthy lifestyle and a normal weight are fundamental to preventing foot pain at an early age in patients with JIA and improving their quality of life.


Dicoma anomala is a medicinal plant that is known for its excellent ethnomedicinal uses which include treatment of coughs, fever, ulcers, and dysentery. This data in Brief article provides information on the diversity of bacterial endophytes associated with a medicinal plant, Dicoma anomala targeting the 16S rRNA gene using Illumina sequencing technology during three different seasons. Plant samples were collected in Eisleben, Limpopo province, South Africa, in the months of April, June, August and October 2018. The dataset revealed that the leaf samples collected in August had the highest species diversity as indicated by the Shannon index (4.25), Chao1 (1456.01), abundance-based coverage estimator (ACE) (1492.07) and the Simpson indices of diversity (0.05) irrespective of the species. The order of the bacterial endophyte's richness in D. anomala was April> October> June> August, from lowest to highest. The taxonomic composition analysis showed that most endophytic bacteria were composed of Proteobacteria, Actinobacteria, Firmicutes, Bacteroidetes and Chloroflexi. Some endophytic bacteria were found to be tissue specific. Sequences of Cutibacterium, Acinetobacter and Methylobacterium were prevalent in the leaves, whereas Amycolatopsis and Bradyrhizobium were the dominant genera in the root samples.Plants harbor varied communities of bacterial endophytes which play a crucial role in plant health and growth.  Endophytes are an essential component of the plant micro-bionetwork as they are known to play a vital role in plant growth, health, and productivity Dicoma anomala, targeting the 16S rRNA genes. Illumina sequencing technology was used to reveal the diversity of bacterial endophyte communities, define dominant taxa of bacterial endophytes from Dicoma anomala plant collected at different seasons, and to compare the bacterial endophyte communities hosted in this plant during different seasons in roots and leaves. Dicoma anomala is a medicinal plant that is distributed in Sub-Sahara Africa; in South Africa it is located in Gauteng, Limpopo, and Free-State provinces Metagenomic profiles of endophytic bacteria were isolated from surface sterilized leaves and roots of Following quality filtering, deletion of chimeras, singletons, mitochondrial and chloroplast sequences, a total of 214 060 reads were obtained from 7 samples. One sample was not included in the analysis of bacterial community structure due to a low number of sequence reads. The highest number of reads was obtained from the leaf tissues (85 316) collected in October, followed by the root tissues (60 204) collected in April. The leaves also had a lower number of reads (311) in April while for the roots the lowest number of reads was obtained in June with 579 reads as shown in Diversity indexes (Shannon and Simpson) between the roots and leaves indicated a significant difference between the roots and the leaves collected in the three seasons (p < 0.5). Although no significant differences were observed in the alpha diversity (Shannon index), we observed a significant difference of diversity of endophytic bacteria which was collected from the different months (seasons) . HoweverProteobacteria, Actinobacteria, Firmicutes, Bacteroidetes and Chloroflexi. Proteobacteria was the most abundant in all the 7 samples (42.83-99.95 %) followed by Actinobacteria (7.21-43.17%), Firmicutes (0.52-20.90 %) and Bacteroidetes (0.11-6.9 %). Chloroflexi was more abundant in leaves collected in August (2.89 %) and in the roots collected in October (2.61%) while in other samples it was found to be at a relative abundance of less than 1%.The most dominant phyla in all the samples were Proteobacteria which were Gamma-proteobacteria (14.68-99.85%) and Alpha-proteobacteria (7.9-34.68%) were found to be the most abundant in all the samples. While Actinobacteria (7.72-35.75%) was the third dominating class in the phyla Actinobacteria. Within the phyla Firmicutes, Bacilli was only dominant in leaves collected in April (19.29%) and in both the roots (5.35%) and leaves (16.58%) collected in June, respectively. However, Planctomycetia, Acidimicrobiia and Bacteroidia were found at a relative abundance of less than 5%.At the class level , two claProteobacteria, Actinobacteria and Firmicutes. The Gamma-proteobacteria, had the highest number of Proteobacteria observed with the largest number of orders isolated  and Enterobacterales (0.4-17.78%) in the class Gamma-proteobacteria. In the Alphaproteobacteria class, the most prominent members included Rhizobiales (2.0-16.26%) and Sphingomonadales (0.01-19.55%). In the Firmicutes class, Bacillales were found to be more abundant in the leaves (19.29%) collected in April and in the roots (5.35%) and leaves (15.76%) collected in June, whereas, in the remaining samples it was found to be at a relative abundance of less than 1%. The order Pseudonocardiales, was found to be more abundant in roots (20.29%) collected in June and it was not detected in the leaves collected in April.To assess the microbial composition, the most abundant phyla observed were isolated . The mosPseudomonadaceae was the most abundant (3.9-99.44%) in all the samples, followed by Sphingomonadaceae (0.11-19.47%) and Bacillaceae (0.17-16.07%). However, Pseudonocardiaceae was more abundant in the roots (20.89%) collected in June whereas, Propionibacteriaceae was more abundant in the leaves (14.79) collected in April and found to be less than 1% in other samples.A total of 18 families were identified. At the family level , PseudomPseudomonas (3.97-99.43%), Sphingomonas (0.01-18.77%) and Bacillus (0.01-16.07%) were the most dominant. In addition, the genera Amycolatopis (20.03%) and Cutibacterium (14.79%) were most dominant in the leaves collected in April whereas, Bradyrhizobium (11.97) was more dominant in the roots collected in June. Other genera such as Pantoea (0.00-5.57%), Methylobacterium (0.6.54%) and Enterobacter (0.912%) were also abundant genera with relative abundances greater than 5% in some samples. At the species level, Pseudomonas fulva species (2.76-68.69%) were the most dominant in all the samples followed by Bacillus cereus (0-13.10%) and Pseudomonas_Uc (0-12.86%).At genus level , the genPseudomonas was the most abundant genus in both the roots and the leaves of D. anomala . Members of the genus Pseudomonas provide important benefits to host plants by synthesizing phytohormones (IAA) and increasing host stress tolerance Acinetobacter, a common soil bacterium was more abundant in the leaves collected in June (winter), whereas Acidibacter was abundant in the roots collected in the same month/season; in the other seasons, these either absent or occurred at a relative abundance of less than 1%. Bacillus was more abundant in the leaves collected in April (autumn) and June (winter), while Bradyrhizobium was found to be abundant in the roots collected in June. Other endophytes were found to be organ specific. Sphingobium was not detected in the leaves of the first two months (April and June); it was only detected in August and was less abundant in October whereas, Methylobacterium was more prevalent in the leaves throughout all the seasons and occurred at a low abundance in the roots. Similar outcomes were observed for the genus, Vulcaniibacterium.We observed that there are some endophytic bacteria that were plant tissue and season specific, whereas others were recovered from all the tissues. 22.1The plant samples were collected from the same site but different plants in April, June, August, and October 2018 in Eisleben, Limpopo province, South Africa (23°31′50.2"S 29°48′46.7"E). Material collection of the plant included leaves and roots; with root collection, the plant was dug with precaution to minimize any damage. Immediately after collection, the plant was placed in sterile polyethylene bags and transported to the lab for further processing. To simplify and compare the differences of endophytic bacteria collected in different seasons, four groups were created as follows: 1) Met_DA1_H1 and Met_DA2_H2 collected in autumn (April), 2) Met_DA3_H3 and Met_DA4_H4 in winter (June), 3) Met_DA5_CA1 in winter (August) and 4) Met_DA7_reLO1 and Met_DA7_RO1 in spring (October).2.22HPO4, and KH2PO4 at pH 7.4). To ensure that epiphytes were removed, small parts of the roots and leaves were cut and plated on NA and incubated at 28 °C for 72 hours. Plates with no growth were selected for DNA extraction. Plant powders were stored at -22°C for future use.Plant roots and leaves were surface sterilized following the protocol by Hassan 2.3−1 final concentration) was added to the supernatant and inverted. The tubes were incubated at room temperature for 20 min followed by centrifugation at 12 000 rpm for 5 min to recover the metagenomic DNA. The supernatant was discarded and pellets air dried. The DNA pellets were washed twice with 250 µL of 70% ethanol and centrifuged at 12 000 rpm for 5 min before drying in a laminar flow. The DNA was re-suspended in 50 µL nuclease free water and quantified using a Nanodrop ND-2000 UV-Vis spectrophotometer  before storage at -20°C for future use.Total metagenomic DNA extraction was performed using the modified method described by Murray and Thompson 2.4The PCR library preparation involved steps to amplify the V3 and V4 regions using the 2X KAPA HiFi Hot Start Master Mix PCR kit and NextEra® XT index kit for attachment of dual indices and Illumina sequencing adapters. Hypervariable regions V3-V4 of the 16S rRNA gene were amplified using the forward primer:  5ʹ-CCTACGGGNGGCWGCAG-3ʹ and reverse primer 5ʹ-GACTACHVGGGTATCTA-3ʹ. The PCR reactions were performed with a 25 µL reaction containing 2.5 uL (5ng/uL) of genomic DNA, 5 uL of each primer (10 μM), 10.5 μL of 2 × KAPA HiFi HotStart MasterMix and 2μL of nuclease free water. The PCR reaction was carried out using the following conditions: initial denaturation at 95°C for 3 minutes followed by 25 cycles at 95°C for 30 s, 55°C for 30 s, and 72°C for 30 s and final extension at 72°C for 5 min. The PCR product was verified by running 1uL on a Bioanalyzer DNA 1000 chip. Nextera XT Index kit was used to attach dual indices and Illumina sequencing adapters, AMPure XP beads were used to clean PCR products pre- and post-tagging. The libraries were normalized and pooled prior to sequencing on Illumina MiSeq platform using MiSeq v3 reagent kit. The amplicon metagenomic sequencing was performed at the Biotechnology platform ARC, Onderstepoort, South Africa.2.5de novo Uchime algorithm was used to remove chimera, singletons, mitochondrial and chloroplasts sequences. Operational taxonomic units (OTUs) were build using the furthest neighbor clustering algorithm at a cut-off of 97% sequence similarity and classified using the naive Bayesian classifier which was trained against a customized Ribosomal Database Project (RDP) classifier training set, thus remaining only with bacterial-origin sequences The raw sequencing data of the seven samples were processed according to the Standard Operating Procedure (SOP) pipelines of the software package Mothur with slight modifications 2.6Statistical analysis was performed using the One-way ANOVA to analyze all data obtained. Analysis was carried out using the Statistical Package for Social Science (SPSS) version 16.0 and the means were compared using Turkey's Studentized Range Test (HSD (0.05)) in the R program and p values < 0.05 were considered statistically different.Mehabo Penistacia Maela: Investigation, Software, Methodology, Data curation, Validation, Writing - original draft preparation; Mahloro Hope Serepa-Dlamini: Conceptualization, Supervisor, Writing – review & editing.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


The PI, RI, and VI were significantly lower in the study group than control group (p < 0.0001). No significant associations were observed between seven sonographic parameters and acute simple or/and complex cervicitis. For acute simple cervicitis, a PI cutoff of 1.1 had a sensitivity of 85.4% and a specificity of 92.1% . A RI of 0.6 had a sensitivity of 85.4% and a specificity of 78.9% . A VI of 2.6 had a sensitivity of 85.4% and a specificity of 78.9% . Power Doppler angiography of micro-vessel flow velocity waveforms in the cervix could represent a practical method to assist the diagnosis of pelvic inflammatory disease presented as acute cervicitis detected on transvaginal ultrasound before medical or surgical treatment. Cervical PI may be a useful index to detect micro-vessel flow velocity waveforms in acute cervicitis and differentiate acute simple cervicitis from complex cervicitis.We have conducted cervical imaging of uterine and micro-vessel flow velocity waveforms in acute pelvic inflammatory disease (PID) by transvaginal power Doppler ultrasound (TVPDU) in order to explore the associations of sonographic parameters with simple and complex cervicitis. Thirty-eight patients with acute PID (26 with acute simple cervicitis and 12 with complex cervicitis) were enrolled for an assessment of vascular grading of cervix and micro-vessel flow velocity using TVPDU before treatment. Seven parameters, including vascular grading (VG), lowest pulsatility index (PI), resistance index (RI), peak systolic velocity (PS), end diastolic velocity (ED), time average maximum velocity (TAMV), and vascular index (VI = PS/ED), were measured and recorded. Forty-one healthy patients were assessed as the control group. Vascular grading (VG) was significantly higher in the study group than the control group ( Pelvic inflammatory disease (PID) is a term commonly used to describe inflammation resulting from an infection in the upper genital tract that is not associated with pregnancy or intraperitoneal surgery. Acute PID is caused by an infection ascending along the mucosal surface, which the bacteria colonize. Traditionally, acute PID is assessed quantitatively by measuring the blood flow indices of ovarian, tubal, adnexal masses or uterine vessels using transabdominal or transvaginal color Doppler ultrasound ,2,3. TraThe main aim of this study was to assess the detailed morphology and blood flow velocity of micro-vessels in the cervix by using transvaginal power Doppler ultrasound in patients with PID who presented with acute cervicitis. Moreover, we examined the value of these parameters to differentiate simple cervicitis from complex cervicitis.Fifty female patients with clinically suspected pelvic inflammatory disease (PID) who presented as acute simple cervicitis or complex cervicitis were recruited at Taipei Veteran General Hospital from January 2000 to August 2021. The inclusion criteria were the typical clinically suspected signs of pelvic inflammatory disease, such as the presence of both positive lifting pain and motion tenderness of the cervix on pelvic examination before clinical treatment. Seven cases without these clinical typical signs, three cases without lifting pain and motion tenderness of the cervix, two cases who received NSAID pain relief before arriving at hospital were excluded from this study. A total of 38 cases met the inclusion criteria; the general characteristics of these patients are presented in Among our case group, 26 patients with acute simple cervicitis were categorized into group 1, and 12 patients with acute complex cervicitis into group 2 .All women were scanned using color Doppler ultrasound  equipped for color Doppler imaging and color Doppler angiography in the semi-lithotomy position with an empty urinary bladder within one day before undergoing treatment. A 7.0-MHz curved-array endo-vaginal probe was used; the field of view was set to 112 degrees. The uterine cervix was scanned and identified carefully in longitudinal view in grayscale mode. After shifting to angio mode, the color gain was adjusted from 105 to 115, the scale was adjusted to pulse repetition frequency (PRF) and set at 800–900 Hz to filter out low-strength signals, and the temporal filter was adjusted to 1.0 to exclude the blue color within the region of interest (box). Vascularity within the uterine cervix was detected in axial view.We classified vascularity within the uterine cervix into five grades under power mode color Doppler ultrasound , as follAfter visually classifying the grade of vascularity from the power mode color Doppler ultrasound, we activated pulse Doppler mode and adjusted the Doppler gate over the target color area to set the gate distance appropriately and adjust the angle of the sampling site to less than 65 degrees. We defined detectable Doppler signals as a series of reproducible, similar arterial waveforms obtained for at least three separate, consecutive cardiac cycles.Satisfactory Doppler signals were processed and analyzed using online spectra. All measurements were calculated manually, including peak systolic velocity (PS), end diastolic velocity (ED), time-averaged maximum velocity (TAMVV), the pulsatility index (PI), the resistance index (RI), and the vascular index (VI). If more than one set of satisfactory samples were achieved, the lowest set of PI, RI and VI values were recorded. The pulsatility index was defined as the ratio of the difference between the peak systolic and end diastolic velocity to mean velocity. The resistance index was defined as the ratio of the difference between the peak systolic velocity and end diastolic velocity to peak systolic velocity. The vascular index was defined as the peak systolic velocity divided by end diastolic velocity (PS/ED). All scans were performed and assessed by one author (Y.C.W.) to avoid interobserver and intra-observer variation. This study was approved by the Hospital’s Internal Review Board with IRB No.108062.p-values < 0.05 were considered statistically significant.The vascular grading between study groups and cervical micro-vessel flow waveform parameters were analyzed with Mann-Whitney U test or Kruskal-Wallis test. Post hoc analysis was conducted with and Benjamin-Hochberg procedure. Relationship be-tween vascular grading and waveform parameters were accessed with Spearman’s rank correlation. Clopper-Pearson exact method was used to estimate the testing accuracy confidence intervals. The Statistical Package for the Social Sciences (SPSS) for Windows, version 22.0  was used for data analysis and ROC curve analysis. p = 0.159).The mean age of all 79 individuals included in this study was 34.5 ; all individuals were pre-menopausal. The mean ages of the case group (33.3 ± 7.4) and control group (35.6 ± 6.1) were not significantly different  had acute simple cervicitis and 12 patients  had acute complex cervicitis. Most cases of acute complex cervicitis were acute cervicitis complicated by tubo-ovarian abscesses .The pick-up rate was 100% (38/38) for the case group and 26.8% (11/41) for the control group. The absence of vascularity was classified as grade 0. In the control group, 73.2%, 24.4%, and 2.4% of the individuals were classified as grade 0, grade 1, and grade 2, respectively.Of the 38 patients with acute pelvic inflammatory disease, 25 (65.8%) cases were classified as grade 1 , ten 26, two 5. and one In the visible grading of vascularity for group 1 (acute simple cervicitis), 19 cases  were classified as grade 1, five  as grade 2, one  as grade 3, and one  as grade 4. In group 2, four patients  were classified as grade 1, seven  as grade 2, and one patient  as grade 3.p < 0.000). In three group comparison, Mann Whitney U test with multiple comparison adjustment showed significant differences between cervicitis and control group . The difference be-tween complex and simple cervicitis was insignificant (p = 0.076).The vascular grade has significant difference between acute cervicitis and control group, acute cervicitis group has higher grade than control group (p = 0.000), RI , VI (S/D) , ED , but there is no correlation with PS  and TAMV    .p = 0.0001). Similarly, the mean RI was also significantly different between the study group (0.6± 0.1) and control group . However, the mean VI was significantly different between the study group (2.4 ± 0.5) and control group .The mean PI was significantly different between the study group (0.9 ± 0.2) and control group . PI, RI, and VI differ significantly in the comparison of cervicitis and control group. (p < 0.05). PI differ significantly in the comparison of complex cervicitis vs. simple cervicitis. (p < 0.05)   .A PI cutoff value of 1.1 had a sensitivity of 85.4%, specificity of 92.1%, positive predictive value (PPV) of 91.5%, negative predictive value (NPV) of 86.3%, and accuracy of 93.2% for acute simple cervicitis. A RI cutoff value of 0.6 had a sensitivity of 85.4%, specificity of 78.9%, PPV of 80.2%, NPV of 84.4%, and accuracy of 86.1% for acute simple cervicitis. A VI cutoff value of 2.6 had a sensitivity of 85.4%, specificity of 78.9%, and accuracy of 84.9% for acute simple cervicitis .n = 12) and group 1 (n = 26).B. ROC curve of six sonographic parameters between the group 2  is difficult to diagnose, as most of the symptoms are often mild and subtle . TransvaIn acute PID presenting with simple cervicitis, most vascular hotspots were classified as grade 1 and grade 2  using our visual grading system. Moreover, most cases of complex cervicitis were classified as grade 1 and grade 2  on the visual grading system. That is, if the grading system is greater than or equal to 1, it is regarded as acute cervicitis, the sensitivity can reach 100%, and the specificity can reach 73.1% . These rIn normal healthy cervical tissue, color angio mode 3D ultrasound detects some small vessels in the myometrium, but no other color-coded areas in the submucosal layer, similarly to our observations for grade 0, grade 1, or grade 2. In our control group, 30/41 cases were grade 0, 10/41 were grade 1 and only one case was grade 2. Inflammation due to bacterial or viral cervicitis leads to angiogenesis. A previous study using 3D ultrasound in color angio mode revealed the arterial blood supply of the submucosal layer spreading into an arterial spiral of vessels running down to the portion of cervix, which is compatible with our observations of grade 3 and grade 4 vascularity within the cervix . The 3D n = 20) and a significantly lower PI (0.84 ± 0.04) in the blood vessels of the tubal walls and adnexal masses of women with acute PID than a control group (1.5 ± 0.1) (p < 0.01). Even in different blood vessels, in our study, we also have the similar results about the pick-up rate was 100% (38/38) and a significant lowest mean PI (0.9 ± 0.2) in our case group. Romosan et al. [n = 17), endometriosis (n = 9), cervicitis (n = 3) and unrelated to genital infection (n = 23). A review of the literature from Romosan et al. [The main sonographic parameters ever applied in patients with acute PID, including the pulsatility index (PI), peak systolic velocity (PSV) and time-averaged maximum velocity (TAMV) ,10. Molan et al. . showed p = 0.000), RI , VI  (p < 0.05), but PI is best than RI and VI because it has significant difference between simple cervicitis and complex cervicitis (p < 0.05)  . It is r < 0.05) . AlthougMoreover, gently, and slightly touching, no need to apply the same pressure on the vaginal probe every time , this miVascular grading system using by transvaginal power Doppler angiography can help us quickly diagnose if there is acute hyperemia of cervix. For acute simple cervicitis, a PI cutoff of 1.1 had a sensitivity of 85.4% and specificity of 92.1% . Cervical PI may be a useful index to detect micro vessel flow velocity waveforms in acute cervicitis and differentiate acute simple cervicitis from complex cervicitis. Our study could provide a practical method to assist diagnosing of acute cervicitis detected on transvaginal ultrasound before medical or surgical treatment.