The main objective of this research was to assess the risk factors and causes of ischemic stroke in the young population (age less than 50 years).This was a prospective multicenter study conducted at Pakistan Atomic Energy Commission General Hospital, Islamabad, and Mayo hospital Lahore from June 2019 to June 2020. In this research, patients with ischemic stroke, aged 15–50 years were included. Prior to noting demographics, each patient gave ethical approval via filling out consent forms. After that, all demographical details including residence, education, gender and age, and socioeconomic status were noted. Risk factors were evaluated on the questionnaire proforma. Outcomes were measured using the modified Rankin scale (MRS) score. Additionally, data were analyzed by using SPSS V26. A P-value of <0.05 was set as statistically significant.Out of 80 patients, 53 (66.25%) were male, while 27 (33.75%) were female. Six (7.5%) patients were between the ages of 15 and 25 years, 18 (22.5%) patients were between 26 and 35 years, 48 (60%) patients were between the ages of 36 and 45, and eight (10%) patients were between the ages of 46 and 50. According to this research, hypertension was found to be the most frequently occurring risk factor in 28 participants (35%), Diabetes mellitus in 23 patients (28.75%), dyslipidemia in 20 patients (22.5%), and smoking in 18 patients (22.5%). The etiology remained undetermined in 30 patients (37.5%). Most of the patients (87.5%) reported positive functional outcomes (MRS score 0–2). However, 3 (3.75%) patients died during the study period.This research showed that common risk factors of ischemic stroke in the local young population included hypertension, diabetes mellitus, and smoking, whereas the etiology of stroke remained unidentified in the majority of patients. •This study was conducted to evaluate causes and risk factors of ischemic stroke in young population (age less than 50 years).•This was a prospective multicenter study conducted between June 2019 to June 2020. Patients with ischemic stroke, aged 15–50 years were included.•Out of 80 patients, Hypertension was the most frequently found risk factor in 28 patients (35%), followed by Diabetes mellitus in 23 patients (28.75%), dyslipidemia in 20 patients (22.5%), and smoking in 18 patients (22.5%). The etiology remained undetermined in 30 patients (37.5%).•This research showed that common risk factors of ischemic stroke in the local young population included hypertension, diabetes mellitus and smoking. RenderiThere are many risk factors and etiologies known to be linked with the occurrence of Ischemic stroke, however, there remains a significant percentage in the younger age group with undetermined causes. For example, previous studies conducted in Europe and the United States indicate that ischemic stroke is increasing in younger adults and traditional stroke risk factors common in older adults  are also common in young acute stroke patients . Recent Moreover, numerous researches reported an increase in the occurrence of ischemic stroke in the age group between 30 and 45 years ,9. Altho17This study is in accordance with strocss guidelines [Additionally, evidence suggests developing countries bear over two-thirds of the worldwide burden of stroke . To dateidelines .The aim of this research was to evaluate the risk factors and causes of ischemic stroke in the young population of Pakistan which hasn't been exclusively studied in the past.Objectives: To identify the risk factors and etiology of stroke in young adults less than the age of 50 years.2Study design and Study area: This study was conducted at the Department of Neurology, Pakistan Atomic Energy Commission General Hospital, Islamabad, and Mayo hospital Lahore from June 2019 to June 2020. Patients below 15 years and those with intracerebral hemorrhage, brain injury, venous sinus thrombosis, head trauma above 50 years of age, and previous history of stroke were excluded from this study. This study included 80 patients of both sexes between the ages of 15 and 50 who presented with their very first episode of ischemic stroke. Data were collected from medical records of patients, laboratory investigations, diagnostic tests, radiological images, and reports. After ethical approval and informed consent from patients, comprehensive demographic details including age, residence, socioeconomic status, and sex were recorded on the proforma. “Complete blood count test” (CBC), “Erythrocyte sedimentation rate” (ESR), glycosylated hemoglobin urine test (Hb A1C), “liver function test”, “renal functional tests” and lipid profile were done for all patients at baseline. Patients with indications underwent immunologic investigations (anti-ds DNA and anti-nuclear antibodies) and thrombophilia screening. Echocardiogram, carotid Doppler, and 24 h ECG recording were also undertaken. CT scan brain was performed on all patients at admission. MRI brain with stroke protocol was also done in cases where needed. Dyslipidemia was defined as having total cholesterol over 240 mg/dL and LDL cholesterol over 160 mg/dL while taking a lipid-lowering agent. Additionally, diabetes mellitus was defined as being treated with insulin or oral hypoglycemic agents and having a glycosylated hemoglobin level of less than 6.5%. TOAST criteria were used to classify stroke subtypes . Consideration was given to causes of ischemic stroke. Risk factors were recorded. The outcome measures were evaluated using a modified “Rankin scale score”. The mortality rate was also observed. SPSS V25 was used to examine all of the statistical data. The Chi-square test was applied to check the differences between categorical variables. All variables' percentage, mean, and standard deviation were calculated statistically. P-value of <0.05 was accepted as statistically significant. Work has been reported in line with the STROCSS criteria [criteria .3Out of 80 patients with Ischemic stroke, 53 (66.25%) were found to be male while 27 (33.75%) patients were females. A total of 6 (7.5%) patients were from 15 to 25 years old, 18 (22.5%) from 26 to 35 years old, 48 (60%) from 36 to 45 years old and 8 (10%) were from 46 to 50 years. In this research 45 (56.25%) participants were from rural areas, whereas 35 (43.75%) were from large cities. In addition, 42 (52.5%) patients had a low socioeconomic status, whereas 38 (47.5%) had an intermediate socioeconomic status .Table 1BIn thirty patients, or 77.5%, the most common reason for the ischemic stroke was unknown. Additionally, in 18 (22.5%) patients cardio embolism was found to be a major etiology for the development of stroke. Moreover, in 14 (17.5%), small artery disease was observed which led to the occurrence of stroke. Other causes of stroke included “large artery atherosclerosis” observed in 10 (12.5%), while other 8 (10%) patients experienced stroke due to unknown causes .Fig. 1EtHypertension was the most common risk factor, accounting for 35% of cases, followed by dyslipidemia (25%), diabetes mellitus (23%), vasculitis in 6% of casessmoking (25%), “coronary artery disease” in 4% of cases and, atrial fibrillation in 7% of cases. .Table 2DThe majority of patients, 60 (75%), had two or more risk factors, with the exception of six patients who only had atrial fibrillation and two patients who only had coronary artery syndrome as risk factors. Vasculitis was found a risk factor in 18.52% of the female subgroup.In this research, outcome measures were noted according to the “modified Rankin scale scoring system” and it was observed that 70 (87.5%) patients scored 0 to 2, 5 (6.25%) scored 3–4 and the remaining 5 (6.25%) scored 5–6 .Table 3O4Ischemic stroke is one of the most frequently occurring neurological disorders with significant mortality and morbidity rates globally. Numerous studies have investigated the risk factors and causes associated with ischemic strokes in young populations ,15. HoweIn this research, 52.5% of patients had a low socioeconomic status, whereas 47.5% had an intermediate socioeconomic status. These outcomes were identical to those of other trials in which the majority of young patients had a poor socioeconomic status .This implies that male gender and poor socioeconomic status could be a risk factors for the occurrence of stroke in young individuals. Additionally, in this investigation, the leading cause of ischemic strokes was unknown (77.5%), followed by cardioembolism the secondary major cause 22.5%). Moreover, Khalid Sher et al., found that 25.3% of deaths in young patients were due to cardioembolism, which was the top cause of mortality .5%. More.In this research the most 35% of patients had hypertension, which was the most prevalent risk factor detected, followed by diabetes mellitus (28.75%), dyslipidemia 25%), smoking (22.5%), atrial fibrillation in 6 (7.5%), and coronary artery disease (5%) individuals. These results are identical to another research, Schneider et al. observed 741 cases and found that hypertension was the most common risk factor among young adults. Dyslipidemia (46%) and smoking were the next most common risk factors (35%).Numerous%, smokinIn this research, outcomes were measured using the “modified Rankin scale scoring system’’, and it was observed that 87.5% of patients had scores between 0 and 2,5 whereas 6.2% of patients had scores between 3 and 4, and 6.2% had scores between 5 and 6. These results are similar to a previous trial in which 89% of participants had favorable outcomes with a relatively low death rate .Our study has a few limitations: it included small sample size and further extensive investigations could not be carried out in patients with undetermined etiology due to limited resources.5The study concludes that male patients aged 36–45 years were at higher risk of developing stroke and hypertension was found to be the most commonly found risk factor subsequent to smoking, dyslipidemia, and Diabetes. The cause of stroke in the young population still remains undetermined in the majority of patients. Our study findings emphasize the importance of proactive care of conventional risk factors and comprehensive patient work-up to determine the cause of stroke in young people of Pakistan. Additionally, further longitudinal studies on a larger scale on young stroke are required to understand the potential reasons and risk factors behind stroke development in young patients.This cross-sectional study was approved by the Institutional Review Board by PAEC General Hospital Islamabad.{PGHI-IRB(Me)-RCD-06-001)}There is no source of funding.All authors have contributed equally.N/A.N/A.Dr Ayesha Aslam is guarantor.N/A.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.


Evaluation of the incidence of conjunctival hyperemia or SPK score showed there were no significant changes noted at any time point. The TSQM-9 score demonstrated there was a significant increase for effectiveness after switching from brinzolamide 1% or brimonidine 0.1% to BBFC. After switching from brinzolamide 1% or brimonidine 0.1% to BBFC, there was a significant decrease in the IOP. Patients were aware of the effectiveness of switching from brinzolamide 1% or brimonidine 0.1% to BBFC.We evaluated switching from brinzolamide 1% or brimonidine 0.1% to a fixed-combination of brinzolamide 1% and brimonidine 0.1%, and then determined the efficacy, safety, and satisfaction associated with these changes in glaucoma patients. This prospective, nonrandomized study evaluated a total of 31 enrolled glaucoma patients who underwent treatment with at least brinzolamide 1% or brimonidine 0.1%. Patients were administered a brinzolamide/brimonidine fixed-combination ophthalmic suspension (BBFC) after being switched from their original brinzolamide 1% or brimonidine 0.1% therapy. All other intraocular pressure (IOP)-lowering medications currently being used were continued. IOP, superficial punctate keratopathy (SPK), and conjunctival hyperemia data obtained at baseline and then at 4 and 12 weeks were evaluated. To assess the changes in treatment satisfaction, this study utilized the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). There was a significant decrease in the mean baseline IOP from 15.7 ± 4.9 mmHg to 13.6 ± 4.4 ( Intraochibitors . As it hhibitors . Howeverhibitors  previoushibitors . These fAt the present time, the only fixed-combination glaucoma therapy that does not contain a β-blocker is the brinzolamide/brimonidine fixed-combination ophthalmic suspension . In Japan, the twice-daily administration of BBFC was approved in 2019. However, if insufficient outcomes are obtained in patients treated with brinzolamide 1% or brimonidine 0.1%, the use of BBFC, rather than brinzolamide 1% plus brimonidine 0.1%, might be a better option, as this treatment uses the same eye drop bottle and the same instillation number of drops per day. The administration of BBFC as a twice-daily versus a monotherapy treatment resulted in a significantly greater IOP-lowering efficacy, compared to either of the individual components after 6 months of treatment in a previous multinational, randomized, double-masked clinical trial . We receIn the current study, we investigated the efficacy, safety, and satisfaction in patients who were switched from brinzolamide 1% or brimonidine 0.1% to BBFC.From October 2020 to April 2022, this clinical trial evaluated patients at 6 investigational sites. These sites included Hiroshima University Hospital , Kusatsu Eye Clinic , Hirota Eye Clinic , Nagayama Eye Clinic , Suzuki Eye Clinic , and Sagara Eye Clinic . The Institutional Review Board of the Hiroshima University approved the study protocol (E-2184). In accordance with the principles outlined in the Declaration of Helsinki, all subjects provided their informed written consent to participate in this study.All patients who took part in this study underwent examinations that included visual acuity, refraction, visual field, slit-lamp examination, and gonioscopy. The eligibility criteria used in the study included having an age ≥ 20 years, glaucomatous optic disc changes, and corresponding glaucomatous visual field defects. Glaucomatous optic disc changes were defined as having a vertical cup-disc asymmetry between the fellow eyes that was ≥0.2, a cup-to-disc ratio that was ≥0.6, and an eye that exhibited neuroretinal rim narrowing, notches, localized pallor, or retinal nerve fiber layer (RNFL) defects. Glaucomatous visual field defects were defined according to the Anderson–Patella criteria . FurtherA total of 3 patient visits were scheduled over 12 weeks (day 0 and weeks 4 and 12) during the study period. Patients were deemed eligible for enrollment if at day 0 (baseline) they were using brinzolamide 1% (twice daily) or brimonidine 0.1% (twice daily), after which they were switched to BBFC (twice daily). All other IOP-lowering medications used remained the same . The admIOP measurements, best-corrected visual acuity, and biomicroscopic examinations were performed in all patients at each visit. The same procedure was performed at all centers using a Goldmann applanation tonometer, with measurements of the IOP performed at the same time as the administration of the brinzolamide 1% or brimonidine 0.1%. The primary IOP change observed at 12 weeks from the baseline was defined as the primary efficacy outcome. Before implementing any changes, average baseline IOPs were determined twice prior to switching the patients to BBFC.For biomicroscopy evaluations, slit-lamp examinations were performed in all patients. A 4-point hyperemia grading scale that utilized four different photographs to determine the hyperemia matching was utilized in order to assess the conjunctival hyperemia. The grading on this scale was set as: 0 = no hyperemia, 1 = slight hyperemia, 2 = moderate hyperemia, and 3 = severe hyperemia. During the slit-lamp examinations, corneal epithelial disorder recordings used an A (area) and D (density) grading scale .In order to assess the change in treatment satisfaction, patients were evaluated using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) , which ut-test or a Wilcoxon signed-rank test. TSQM-9 scores are presented as the median and interquartile ranges. All statistical analyses were conducted using JMP software version 16 . A p value less than 0.05 was considered statistically significant. The data are presented as the mean ± standard deviation.The Anderson–Daring test was used to assess the variance equality for the continuous variables. Differences between the baseline and follow-up visits for the obtained results were subsequently assessed utilizing either a Student’s Of the 34 patients who were initially enrolled, the side effects noted included conjunctivitis in 1 patient, blurred vision in 1 patient, and blepharitis in 1 patient within 4 weeks after switching BBFC. Therefore, a total of 3 patients were removed from the overall study analysis. As a result, there were 31 total patients (31 eyes) who completed the 12-week follow-up. p = 0.001), while at 12 weeks it was 13.5 ± 3.9 mmHg (p = 0.002) (p = 0.007) and 14.5 ± 4.1 mmHg (p = 0.03) at 4 and 12 weeks, respectively. In contrast, the IOP at baseline when switching from brimonidine 0.1% to BBFC was 14.0 ± 2.9 mmHg, which then significantly decreased to 12.4 ± 3.1 mmHg (p = 0.008) and 12.2 ± 3.4 mmHg (p = 0.02) at 4 and 12 weeks, respectively.The IOP at baseline was 15.7 ± 4.9 mmHg. The IOP at 4 weeks was 13.6 ± 4.4 mmHg (= 0.002) . AnalysiData assessed when using the AD grading scale along with the conjunctival hyperemia scores are presented in TSQM-9 scores obtained at baseline and at 12 weeks are presented in Although the conjunctival hyperemia and degree of SPK were sustained throughout the 12-week observation period, there was a significant decrease in the IOP values after switching to BBFC from brinzolamide 1% or brimonidine 0.1%. In addition, patients indicated that they were satisfied with the effectiveness of the therapy.If the IOP cannot be successfully lowered to the exact target pressure, but the therapy appears to be tolerated and effective, then the use of an additional drug of a different class needs to be taken into consideration. However, when using multiple topical treatments, there is a chance that this could reduce adherence and potentially increase the exposure to the preservatives contained within the administered agents. Therefore, instead of using two separate instillations of these agents, the preferred treatment is to use a fixed-combination therapy. Moreover, it has been shown in a previous study that after to switching BBFC from brinzolamide or brimonidine, there was a significant decrease in the IOP . Other sThere are several advantages associated when using fixed-combination medication compared to the concomitant dosing of two separate medications. For example, when using two separate medication dosages, this can potentially cause a washout of the first medication, thereby leading to an insufficient therapeutic effect . In ordeThe use of the TSQM-9 to assess patients’ satisfaction with treatments has been shown to be reliable, with this questionnaire having been utilized to evaluate treatment satisfaction assessments for various diseases ,16. In oIn our current study, there were several limitations. First, there was only a small sample size analyzed in this study. Thus, in order to obtain more rigorous, comparative, and definitive evidence and data, multi-center and large-scale trials will need to be undertaken in the future. Another limitation was that the follow-up period in our current study might not have been long enough. Results closer to what is actually observed in routine practice could potentially be obtained by increasing the experimental follow-up period. At the present time, the mean follow-up period after switching to BBFC was 17.5 ± 8.7  months. Of the 31 patients who were analyzed in this study, the side effects included conjunctivitis in 2 patients, at 6 and 11 weeks after switching to BBFC; blepharitis in 3 patients, at 4, 6, and 24 months after switching; and episcleritis in 1 patient after the 12 week-evaluation period. There were 2 patients that had an insufficient IOP and thus, subsequently underwent glaucoma surgery at 5 and 14 months after switching to BBFC. Third, when switching from brinzolamide or brimonidine to BBFC, there are presently no defined criteria with regard to how this needs to be implemented. All of these changes were strictly made based on the decision of the attending physicians. The progression of glaucomatous visual field damage due to an insufficient IOP was the primary reason why patients were switched to BBFC.In conclusion, after switching to BBFC from brinzolamide 1% or brimonidine 0.1%, the current results showed that there was a significant decrease in the IOP. Furthermore, patients were aware of the effectiveness of this change in their therapy after switching to BBFC from brinzolamide 1% or brimonidine 0.1%.


A meta-analysis from 2016 estimates prevalence of hepatitis C to be superior in people with severe mental illness than general population. In France, positivity for hepatitis C is estimated at 0,75% of general population and 0.3% with a detectable viral load. No recent study was conducted to determine seroprevalence of hepatitis C in population admitted in psychiatric institution.The aims of this study are to determine seroprevalence of hepatitis C in population admitted in psychiatric institution and describe the profile of infected patients.From january 2020 to october 2020, screening test for hepatitis C, hepatitis B and HIV was proposed to every patient admitted at the reception unit of Ravenel Hospital. In case of positivity, viral load was realised.th and Octobre 1st , 407 patients greed to the screening test. Among them, 17  were tested positive to hepatits C and viral load was detectable in 9/17 positives, which lead to a 2,2% seroprevalence of hepatitis C infection in the studied population. The patients with positive screening had a mean age of 40 years old. 82% of them were males. 16 admit using intoxicating substances and 10 were still current users at the time of the study. They were hospitalized for addictology purpose (5/17), psychosis (6/17), mood disorder (5/17), personality disorder (2/17), adjustement disorder (2/7). 10/17 had an alcohol use disorder.Between January 7This study confirms seroprevalence of hepatitis C infection in psychiatric population is seven times that of general population. This justifies a systematic screening of this population.No significant relationships.


The aim was to assess clinical improvement after US-guided injection of CSs into the SI joint of patients with SpA.t-test for the variables visual analog scale (VAS), BASDAI, ASDAS, CRP and ESR before and after the procedure. We evaluated the association between these variables and the clinical response using the odds ratio.This was an observational, descriptive, retrospective study of patients with SpA and sacroiliitis who received an US-guided injection into the SI joint between 1 June 2020 and 31 May 2021. Means were compared using Student’s paired P < 0.0001) and BASDAI 3.24 (1.6) . At 5–6 months, 59.37% had improved: VAS 4.63 (2.31) , BASDAI 3.57 (1.67)  and ASDAS 2.27 (0.71) . Bone marrow oedema resolved in 87.5% of cases compared with the previous MRI scan. No significant association was identified with the clinical response to the injection.We analysed 32 patients with SpA , with a VAS score of 7.88 (0.79), BASDAI of 5.43 (1.48) and ASDAS of 3.27 (0.86) before the procedure. At 2–3 months, 75% of patients had improved: VAS 3.81 (2.33) (−4.07, US-guided injection of CSs into the SI joint of patients with SpA and active sacroiliitis leads to an improvement in symptoms that is maintained at 5–6 months. The procedure is effective, safe, inexpensive and easy to apply. Key messagesThis is the first study carried out in Spain on this procedure in this group of patients and whose outcome variables include activity measurements.US-guided CS infiltration of the SI joint in patients with SpA could be a therapeutic alternative for those in whom clinical and radiological sacroiliitis predominates.The incorporation of US into daily clinical practice would allow the performance of this procedure.The term SpA covers a group of chronic inflammatory rheumatic diseases that mainly affect the axial skeleton . The worImaging-guided CS injection has been considered an effective therapy for >20 years . This apThe few studies performed in patients with SpA have mainly evaluated the improvement in pain using a visual analog scale (VAS) and are limited by the need for an operating room and guidance based on fluoroscopy, tomography or magnetic resonance . The advThe primary objective of this study was to determine clinical improvement  after US-guided injection of CSs into the SI joint of patients with SpA.We performed an observational, descriptive and retrospective study at Ciudad Real General Teaching Hospital (HGUCR), Ciudad Real, Spain.We reviewed the register of procedures carried out between 1 June 2020 and 31 May 2021 and included all patients fulfilling the Assessment of SpA International Society (ASAS) classification criteria for SpA with inflammatory low back pain resulting from sacroiliitis despite treatment with NSAIDs, biologics, or both. We excluded patients whose clinical history did not contain the study variables and in whom modifications to pharmacological treatment could have reduced the effectiveness of the injection.All patients underwent US-guided injection of the SI joint with 12 mg betamethasone chronodose (6 mg acetate/6 mg phosphate) in each joint. The patient was placed in the prone position, with a pillow underneath the abdomen to minimize lumbar lordosis. A low-frequency curvilinear transducer was used. The transducer was placed transversely over the lower part of the sacrum , and the lateral edge of the sacrum was identified. The transducer was moved laterally and cephalad until the bony contour of the ileum was clearly identified. The cleft seen between the medial border of the ileum and the lateral sacral edge represented the SI joint. A 22-gauge needle was inserted at the medial end of the transducer and advanced laterally under direct vision in plane with the US beam until it was seen entering the joint .t-test) for the variables VAS, BASDAI, ASDAS, CRP and ESR. The potential association between the variables and a favourable clinical response was evaluated by calculating the odds ratio. All analyses were performed with a 95% CI using StatPlus v.7.3.32 from AnalystSoft Inc. (USA).We recorded data for the study variables  from the clinical history before the procedure and for 6–8 months after it. The outcome measures were the presence of adverse effects/complications, reduction in the VAS score for inflammatory pain (>0 = 3 points), reduction of ≥1.1 points in the ASDAS, reduction of ≥2 points in the BASDAI, and reduction of CRP and ESR values. These data were analysed by comparing means  reduction of ≥3 points in the VAS for low back pain [3.81 (2.33)]  and an improvement in the BASDAI value in 65.62% [3.24 (1.6)] . At ∼6 months, the improvement in pain remained unchanged, at 59.37% for the VAS [4.63 (2.31)] , 46.87% for BASDAI [3.57 (1.67)]  and 43.75% for ASDAS-CRP [2.27 (0.71)] , whereas only 18.75% experienced a considerable improvement in ASDAS-CRP (reduction ≥2). Most patients reported some degree of subjective benefit of the procedure for ≤8 months. No very significant reductions were recorded for acute-phase reactants: CRP, 0.28 (0.33) ; and ESR, 7.91 (6.55) . After the procedure, only eight patients had undergone a follow-up MRI scan of the SI joint at 5.88 (1.25) months. Compared with the previous scan, bone marrow oedema had resolved in 87.5%.We observed an improvement in 75% of patients at 2–3 months, with a mean , peripheral and extra-articular manifestations, and type of treatment]. However, all the patients whose symptoms improved  had had bone marrow oedema on their MRI scan <1 year before the treatment.Only five patients experienced injection site pain, which lasted 1–2 days. No other adverse effects were reported.et al.  until 6 months, whereas no significant reduction was observed in the placebo group [7.0 (0.6) to 5.2 (0.5)]. Subsequent studies with fluoroscopy-guided injection reported similar results, mainly with respect to the VAS score [In the 1990s, Maugars et al.  first reet al.   based on the VAS score and in inflammation based on MRI at 8 months [P < 0.05) [Braun et al.  reported8 months , 17. Var8 months , and bon8 months , 19. Stu < 0.05) , 20.A systematic review of PubMed performed in 2019 to identify articles on injection of CSs into the SI joint of patients with SpA/sacroiliitis dating from 1990 yielded 46 references, corresponding to 468 injections in 268 patients. Inflammatory pain and stiffness improved in 80% of patients, with a mean duration of 6–8 months. The factors associated with an improved response were shorter time since diagnosis and MRI-based evidence of bone marrow oedema in the joint at baseline . FinallyP < 0.0001), BASDAI  and ASDAS . In line with other authors, we recorded no significant changes in levels of CRP or ESR. However, bone marrow oedema resolved in 87.5% of patients who underwent MRI after the procedure (Rheumatology Advances in Practice online).Our results are consistent with those reported elsewhere, indicating reduced low back pain (VAS score) in 75% and reduced disease activity, which is clearly significant during the first 2–3 months and is maintained at ∼6 months according to the VAS score (−3.25, Our results enable us to conclude that US-guided injection of the SI joint is a safe, effective, inexpensive and easy complementary technique in patients with SpA and recent-onset sacroiliitis that does not respond to standard treatment. Therefore, procedures of this type should be added to the rheumatologist’s therapeutic arsenal.rkac036_Supplementary_DataClick here for additional data file.


The Weibull function was the best mathematical model to describe the in vitro release performance of furosemide in the three USP dissolution apparatuses. These results could be used to manufacture better furosemide dosage forms and decrease the negative clinical impact of current furosemide formulations.Furosemide is a diuretic drug widely used in chronic renal failure. The drug has low solubility and permeability, which cause clinical problems. Studying the in vitro release performance elucidates the rate and extent of drug dissolved from dosage forms under different conditions. Furosemide reference tablets were tested using USP Apparatuses 1 and 2 as well as the flow-through cell method (USP Apparatus 4), a dissolution apparatus that simulates the human gastrointestinal tract better than the other methods. Dissolution profiles were created with USP Apparatuses 1 and 2 at 25, 50, and 75 rpm and 900 mL of 0.1 M hydrochloric acid, acetate buffer (pH 4.5), and phosphate buffer (pH 6.8). USP Apparatus 4 with a laminar flow of 16 mL/min and 22.6 mm cells was used. Drug dissolution was quantified at 274 nm for 60 min. Mean dissolution time, dissolution efficiency, time to 50% dissolution, and time to 80% dissolution data were used to compare dissolution profiles. Additionally, zero-order, first-order, Higuchi, Hixson-Crowell, Makoid-Banakar, and Weibull models were used to adjust furosemide dissolution data. Between USP Apparatus 1 and 2, significant differences were observed in almost all parameters at 50 and 75 rpm (p < 0.05). A similar dissolution profile (f Ka = 3.8) with low solubility and permeability [Furosemide is a diuretic drug widely used in the treatment of oedematous states associated with cardiac, chronic renal failure, hypertension, congestive heart failure, and cirrhosis . Furosemeability . Accordiet al. [in vitro dissolution study of 13 brands of furosemide tablets (40 mg), of which only four fulfil the Q pharmacopoeial specification. Stüber et al. [in vitro dissolution performance than the reference in each of following conditions: pH 7.8/paddle at 25 rpm, pH 7.8/paddle at 50 rpm, pH 5.3/paddle at 50 rpm, and flow-through cell (100 mL/h)/pH 7.8. The difference in in vitro dissolution is more pronounced at pH 5.3/paddle at 50 rpm. Currently, the official dissolution test for furosemide tablets is the USP Apparatus 2 at 50 rpm with 900 mL of phosphate buffer pH 5.8 and no less than 80% should be dissolved at 60 min [in vivo bioequivalence of furosemide solid oral dosage forms by in vitro dissolution studies; however, given the available data, Granero et al. [Factors that affect drug bioavailability related to the pharmaceutical dosage form and manufacturing process have been described , 5. Techet al.  reportedr et al.  studied t 60 min . A biowain vitro release performance using different agitation rates, dissolution media, and dissolution apparatuses provides important information for improving the manufacture and evaluation of generic formulations. Despite the wide use of USP basket and paddle apparatuses  to monitor the physical quality of tablets and capsules, several investigations about the hydrodynamic environment that surrounds oral formulations have reported that these USP apparatuses do not adequately reproduce the natural environment of the gastrointestinal tract [in vitro release performance of poorly soluble drugs under different conditions to establish, in the best possible way, the environment in which the solid dosage forms will be within the gastrointestinal tract. Further, alternative apparatuses must be developed to achieve this goal. The flow-through cell method (USP Apparatus 4) has been introduced as a dissolution apparatus to elucidate the rate and extent of the dissolution of drugs with low solubility under sink conditions [in vitro/in vivo correlation (IVIVC) has been established between the in vitro data generated with this apparatus and in vivo parameters [Low solubility and permeability are problematic characteristics of class IV drugs; thus, the determination of al tract -15; thusnditions . USP Appnditions , and it nditions . Furtherrameters , 20.in vitro release performance of furosemide reference tablets in the hydrodynamic environments generated by different USP apparatuses and dissolution media of physiological relevance to identify the rate and extent of furosemide dissolution under these conditions. This information will reflect the characteristics of the reference drug product that can be considered in the preparation of a generic formulation. Lasix® tablets were tested with 0.1 M hydrochloric acid, acetate buffer (pH 4.5), and phosphate buffer (pH 6.8) using USP Apparatuses 1 and 2 (at different agitation rates) and USP Apparatus 4.The aim of this study was to evaluate the Lasix® furosemide tablets  were used. Mexican health authorities have designated this formulation as a reference product to be used in dissolution and bioequivalence studies .Hydrochloric acid, sodium acetate, acetic acid, and phosphate salts were purchased from J.T. Baker-Mexico . Furosemide reference standard was purchased from Sigma-Aldrich Co. . All samples were filtered through 0.45 μm nitrocellulose filters . Standard solutions were prepared by serial dilutions of the stock solutions of furosemide (1 mg/mL) to achieve concentrations of 1.25–20 μg/mL. The dissolution media comprised 0.1 N hydrochloric acid, acetate buffer (pH 4.5), and phosphate buffer (pH 6.8).Content uniformity and assay tests were performed with the drug product according to the procedures described in the USP .Dissolution profiles of furosemide were obtained using USP Apparatuses 1 and 2  with 25, 50, and 75 rpm agitation rates. Additionally, pharmacopoeial dissolution conditions (USP Apparatus 2 at 50 rpm with phosphate buffer (pH 5.8)) were tested . An ultrDissolution profiles of furosemide were obtained with USP Apparatus 4  with 22.6 mm cells (i.d.). The laminar flow (originated with 6 g of glass beads) of 16 mL/min was tested. The dissolution media also comprised 0.1 M hydrochloric acid, acetate buffer (pH 4.5), and phosphate buffer (pH 6.8) at 37.0 ± 0.5 °C. Samples were taken automatically every 5 min for 60 min. Dissolved furosemide was quantified in a UV/Vis spectrophotometer  with 1 mm cells at 274 nm. For every trial, and depending on the schedule work, a standard calibration curve in 0.1 N hydrochloric acid, acetate buffer (pH 4.5) or phosphate buffer (pH 6.8) was prepared.Dissolution profiles were compared with model-independent and model-dependent approaches. For model-independent comparisons, mean dissolution time (MDT) and dissolution efficiency (DE) were calculated. MDT is the time to dissolve 63.2% of the drug and was calculated according to the statistical moment’s theory , 23. Otht50%) and time to 80% dissolution (t80%) were calculated. The fit was calculated using SigmaPlot software (version 11.0). For a complete comparison of dissolution data by a model-dependent approach, dissolution data were fitted to zero-order, first-order, Higuchi, Hixson-Crowell, Makoid-Banakar, and Weibull models. The model with the highest adjusted determination coefficient (R2adjusted) and lowest Akaike information criterion (AIC) is the best-fit model [For model-dependent comparisons, dissolution data were adjusted to a hyperbole equation (y = ax/b+x) and, using a and b parameters, time to 50% dissolution  and that in the assay test was 100.79%  .Dissolution profiles of furosemide obtained with the USP Apparatuses 1 and 2 at different agitation rates and in different dissolution media are shown in A limited amount of furosemide dissolved in 0.1 M hydrochloric acid at 60 min with both USP dissolution apparatuses (< 20%). Almost 60% of the drug dissolved using USP Apparatus 2 at 75 rpm with acetate buffer (pH 4.5) as the dissolution medium. A complete release of the drug was achieved using phosphate buffer (pH 6.8) at 50 and 75 rpm, independent of the USP apparatus used. To compare dissolution profiles between USP Apparatuses 1 and 2, model-independent and -dependent parameters, at pH 6.8, were calculated, the results of which are shown in t80% was not calculated. At this agitation rate, significant differences in MDT values were observed (p < 0.05). At 50 rpm, significant differences in all calculated parameters were observed (p < 0.05). These results suggest a complete non-equivalence in the dissolution performance of furosemide between USP Apparatuses 1 and 2 at these conditions (pH 6.8 and 50 rpm). At 75 rpm, significant differences in MDT, DE, t50%, and t80% values were observed (p < 0.05). Higher values of MDT, t50%, and t80% were observed with USP Apparatus 1 than with USP Apparatus 2, at 50 and 75 rpm; these findings could be attributed to slower in vitro dissolution rates in USP Apparatus 1. Dissolution data at pH 6.8, adjusted with different mathematical models, are shown in At 25 rpm and with both USP apparatuses, less than 65% of furosemide dissolved; thus, the R2adjusted and lower AIC values), the Weibull function was the best mathematical equation to describe all dissolution data at pH 6.8. The expression of this function is as follows [Considering the established criteria to choose the best-fit model  indicated that USP Apparatuses 1 and 2 at 50 and 75 rpm generated different dissolution profiles. As both USP dissolution apparatuses and agitation rates created different hydrodynamic environments, these results were expected.Model-dependent comparisons , phosphate buffer (pH 6.8), and laminar flow of 16 mL/min are shown in With the flow-through cell method, less than 20% of furosemide dissolved when 0.1 M hydrochloric acid and acetate buffer (pH 4.5) were used, whereas almost 90% of the drug was released with phosphate buffer (pH 6.8). Slower dissolution rates with USP Apparatus 4 than with USP Apparatuses 1 and 2 have been found; however, in this case, a dissolution medium with low pH was an important factor for the low dissolution of furosemide. As more than 80% of the drug dissolved at 60 min at pH 6.8 and, for comparative purposes, the dissolution profile of furosemide tablets was obtained using a pharmacopoeial method. A test was carried out with USP Apparatus 2 at 50 rpm with 900 mL of phosphate buffer (pH 5.8) (Q = 80% at 60 min), the results of which are shown in f2 > 50). This result suggested that a pharmacopoeial method (USP Apparatus 2) can produce a similar dissolution profile to that obtained with equipment (USP Apparatus 4) that generates a hydrodynamic environment similar to that inside the gastrointestinal tract and for which a correlation with in vivo data has been shown [Under official conditions, the furosemide tablets met the Q pharmacopoeial specification (> 80% dissolved at 60 min). The dissolution profiles of USP Apparatuses 2 and 4 were similar , whereas there was no difference in MDT and t50%, between USP Apparatuses 2 and 4. If we consider MDT and t50% as parameters that reflect the in vitro dissolution rate, this is similar between the conditions (USP Apparatus 2 at 50 rpm and phosphate buffer (pH 5.8)/USP Apparatus 4 with a laminar flow of 16 mL/min and phosphate buffer (pH 6.8)), at least until the time at which 63.2% of the drug is dissolved. Furosemide dissolution data obtained with pharmacopoeial conditions and the flow-through cell method, adjusted to mathematical models, are shown in Significant differences were observed in percent dissolved at 60 min, DE, and in vitro release performance of furosemide reference tablets in these two dissolution apparatuses. Weibull parameters and Td values are shown in The Weibull function was the best-fit model to describe the in vitro release performance was achieved based on f2, MDT, t50%, and Td comparisons.The dissolution of furosemide reference tablets using USP Apparatus 4 exceeded the Q pharmacopoeial criterion (only at pH 6.8) set for certain conditions in the USP Apparatus 2. When the dissolution data of USP Apparatus 4 were compared with those of USP Apparatus 2 (50 rpm and phosphate buffer pH 5.8), an equivalent β = 1); sigmoidal, with upward curvature followed by a turning point (β > 1); or parabolic, with steeper initial slope consistent with exponential (β < 1) [β values > 1, meaning sigmoidal profiles.Under all conditions used, furosemide dissolution profiles were well described by Weibull function. The shape factor of the Weibull function characterises the dissolution profile as exponential ( (β < 1) . In thiset al. [et al. [et al. [in vitro dissolution rate correlates with the in vivo absorption rate only at a low agitation rate (55 rpm). These results support the search for better dissolution schemes, especially with drugs with poor solubility. Poor permeability is a problem in the design of solid oral dosage forms with good bioavailability; thus, it is important to understand the influence of agitation rate, USP apparatus, and dissolution media on the in vitro release performance of class IV drugs.Several authors have studied the effect of the hydrodynamic environment on the tablet dissolution rate. Wu et al.  studied  [et al.  stated t [et al.  concludein vitro release of a hydrosoluble drug can be accurately controlled through the USP apparatus. Shabir worked with atenolol (class III drug) generic tablets using USP basket and paddle apparatuses. Although these dissolution apparatuses are currently the most popular methods, Gao [The search for adequate dissolution conditions is not limited to poorly soluble drugs or the use of USP Apparatuses 1 and 2. Shabir  indicateods, Gao  explainsods, Gao .in vivo conditions; 3. it simulates intraluminal hydrodynamics efficiently; 4. it can be modified for different dosage forms; and 5. it measures the in vitro release rate profile as an output that is similar to the shape of an in vivo profile [in vitro release study of furosemide reference tablets, we used only the flow rate of 16 mL/min as the Sotax equipment model CE6 has a working flow range of 10‒50 mL/min.USP Apparatus 4 has several advantages: 1. sink conditions can be maintained for poorly soluble drugs throughout the dissolution run; 2. it is easy to change media  and modify flow rate to simulate  profile . America profile . In thisBased on these characteristics, it is possible to establish a meaningful IVIVC with USP Apparatus 4. When a meaningful IVIVC has been established, it can be used as a surrogate for and to minimize the number of bioequivalence studies during drug product development . Some aut50%, and t80% were calculated. At 50 rpm, significant differences in all calculated parameters (USP Apparatus 1 vs. 2) were observed. Differences between both USP apparatuses were expected owing to the different hydrodynamics of each apparatus; however, it is necessary to understand at what agitation rate this difference is more evident. Despite the wide use of USP Apparatuses 1 and 2 at different agitation rates, they have still been evaluated by several authors in terms of the surrounding hydrodynamic environments, which do not adequately reproduce the natural environment of the gastrointestinal tract [Some drugs can be dissolved using dissolution media in the physiological pH range  or biorelevant media, such as FaSSIF and FeSSIF  , to docual tract , 32, 40.in vitro release performance of furosemide reference tablets. These models were used to facilitate the analysis and interpretation of dissolution data because they describe the dissolution profiles as a function of the few parameters that can be statistically compared [et al. [The fitting of dissolution data to mathematical models was carried out without any physiological significance to discover the best equation to explain the compared . Han et  [et al.  documentin vitro studies, they provide a good estimate of the absorption rate of class II drugs. Several authors have shown this important association only with USP Apparatus 4 [The development of more discriminative methods than using pharmacopoeial conditions to evaluate the biopharmaceutical quality of generic formulations has been documented. Studies with class II drugs, such as carbamazepine , meloxicaratus 4 , 20, 35.aratus 4  and ibuparatus 4 . These rin vitro release performance of furosemide reference tablets was determined using USP Apparatuses 1 and 2 at different agitation rates and dissolution media of physiological relevance. A limited amount of furosemide dissolved with both at pH 1.2 and 4.5. Better results were obtained with a dissolution medium of pH 6.8. Although USP basket and paddle apparatuses are the most widely used, it is important to take advantage of USP Apparatus 4 for the evaluation of furosemide tablets under the hydrodynamic environment that this equipment generates. All information collected is important to reduce the negative clinical impact that this class IV drug presents. This furosemide reference product is the comparative formulation for generic drug products; thus, it is important to understand the in vitro release performance under all possible schemes for the design of better commercial formulations.The


Background and Objectives: In October 2018, the International Federation of Gynecology and Obstetrics (FIGO) revised its classification of advanced stages of cervical cancer. The main points of the classification are as follows: stage IIIC is newly established; pelvic lymph node metastasis is stage IIIC1; and para-aortic lymph node metastasis is stage IIIC2. Currently, in Japan, radical hysterectomy is performed in advanced stages IA2 to IIB of FIGO2014, and concurrent chemoradiotherapy (CCRT) is recommended for patients with positive lymph nodes. However, the efficacy of CCRT is not always satisfactory. The aim of this study was to compare postoperative adjuvant chemotherapy (CT) and postoperative CCRT in stage IIIC1 patients. Materials and Methods: Of the 40 patients who had undergone a radical hysterectomy at Iwate Medical University between January 2011 and December 2016 and were pathologically diagnosed as having positive pelvic lymph nodes, 21 patients in the adjuvant CT group and 19 patients in the postoperative CCRT group were compared. Results: The 5 year survival rates were 77.9% in the CT group and 74.7% in the CCRT group, with no significant difference. There was no significant difference in overall survival or progression-free survival between the two groups. There was no significant difference between CT and CCRT in postoperative adjuvant therapy in the new classification IIIC1 stage. Conclusions: The results of the prospective Japanese Gynecologic Oncology Group (JGOG) 1082 study are pending, but the present results suggest that CT may be a treatment option in rural areas where radiotherapy facilities are limited. Cervical cancer is the seventh most common cancer in humans and the fourth most common cancer in women. According to the Agency for Research on Cancer (IARC) database in 2018, the global incidence of cervical cancer was approximately 569,000, and the global mortality was 311,000 . Matoda A total of 40 patients with cervical cancer were treated from 2012 to 2016 at Iwate Medical University Hospital. All patients underwent radical hysterectomy (type III) and pelvic lymphadenectomy before CCRT or CT. The patients were FIGO stage IIIC1 (positive pelvic nodes).2. The median number of cycles per patient with CDDP was 5 (range: 2–5). CDDP was given for >180 min. Renal function and blood counts were assessed before each cycle. Adjuvant treatment was started approximately 7 weeks later .Postoperative radiotherapy consisted of external beam radiotherapy (EBRT). EBRT was delivered with anteroposterior- and posteroanterior-opposed beams generated by an X-ray accelerator with an energy of 10 MV at a distance of 100 cm. The superior margin of the external radiation field was located at the top of the L4-5 vertebrae, and the inferior margin was located at the inferior border of the obturator foramen. The lateral margin was 1.5–2 cm lateral to the widest margin of the bony pelvis. Whole pelvic irradiation was delivered at 2 Gy/fraction for 5 fractions/week, for a total of 25 fractions (50 Gy). CT was given intravenously weekly during the course of radiotherapy. The first administration was performed on the first day of radiotherapy. The dose of cisplatin (CDDP) was 40 mg/m2 on days 1 and 8, and NDP 80 mg/m2 on day 1), and the cycles were repeated every 28 days. CPT-11 was given over 1.5 h, and NDP was given over 1 h. The median number of cycles per patient with CPT-11/NDP was 6 (range: 5–6). Four patients received CPT-11/CDDP , and the cycles were repeated every 28 days. CPT-11 was given over 1.5 h, and cisplatin was given over 1.5 h. The median number of cycles per patient with CPT-11/CDDP was 5 (range: 4–6). Four patients received PTX/NDP (PTX 175 mg/m2 and NDP 80 mg/m2 on day 1), and the cycles were repeated every 28 days. Paclitaxel was given over 3 h, and nedaplatin was given over 1 h. The median number of cycles per patient with PTX/NDP was 5 (range: 3–5). Five patients received docetaxel (DTX)/ carboplatin (CBDCA) (DTX 70 mg/m2 and CBDCA AUC5 on day 1), and the cycles were repeated every 21 days. DTX was given over 1 h, and CBDCA was given over 1 h. The median number of cycles per patient with DTX/CBDCA was 6 (range: 3–6). Four patients received PTX/CBDCA (PTX 175 mg/m2 and CBDCA AUC6 on day 1), and the cycles were repeated every 21 days. PTX was given over 3 h, and carboplatin was given over 1 h. The median number of cycles per patient with PTX/CBDCA was 6 (range: 5–6). Adjuvant treatment was started approximately 6 weeks later .Chemotherapy was administered intravenously. Five patients received CPT-11/NDP  was used for all statistical analyses.The survival analysis was based on the Kaplan–Meier method, and the results were compared using the log-rank test. The recurrence rates were compared using Fisher’s exact test. Significance was set at Patient characteristics are shown in p = 0.9751, Hazard ratio [HR]: 1.020, 95% confidence interval [CI]: 0.2885–3.605), and overall survival rate (OS)  were not significantly different. As shown in p = 0.6539, HR: 0.6481, 95% CI: 0.087–4.819) and OS  were not significantly different. As shown in p = 0.7173, HR: 0.7617, 95% CI: 0.1633–3.553) and OS  were not significantly different. In addition, no statistically significant difference RFS and OS were found between CCRT and CT in parametrium invasion . In the CCRT Group, 4 patients recurred outside the pelvis, and 1 patient recurred both in the pelvis and outside the pelvis. In the CT group, 1 patient recurred in the pelvis, 3 patients recurred outside the pelvis, and 3 patients recurred both in the pelvis and outside the pelvis.As shown in As shown in This paper is the first comparison of CCRT and CT in FIGO2018 stage IIIC1 cervical cancer. The present study found no significant differences in OS and PFS between CCRT and CT for cervical cancer patients with FIGO stage IIIC1. Adjunctive CT after radical hysterectomy was shown to be an effective treatment.In the current retrospective study of CT, the 4 year PFS and 4 year OS were 71.3% and 77.9%, respectively. Radiotherapy or CCRT have been performed in postoperative cervical cancer patients with lymph node metastasis. CCRT has already been shown to significantly meliorate prognosis in comparison to radiotherapy alone. The GOG109/AWOG87-97 trial was a prospective study that explored the efficacy of CCRT for postoperative cervical cancer patients with risk factors for recurrence. GOG109 showed that the estimated 4 year PFS and OS were 80% and 81%, respectively ,12,13,14In the present study, because the CT regimen was reviewed on a case-by-case basis, the CT regimen was not standardized. Various regimens for postoperative adjuvant CT have been investigated in cervical cancer. Takekuma et al. reported a phase II study of adjuvant CT with PTX and NDP for uterine cervical cancer with LN metastasis . This stThe present results showed that there was no significant difference in efficacy between CT and CCRT for postoperative treatment in FIGO2018 stage IIIC1 cervical cancer. Moreover, these results suggested that there was no significant difference in efficacy between CT and CCRT for postoperative treatment of parametrium-positive patients in FIGO2018 stage IIIC1 cervical cancer. Systemic CT has potential as a postoperative treatment choice for FIGO2018 stage IIIC1 cervical cancer.


To evaluate the safety and efficacy of radiofrequency ablation (RFA) for metastatic lymph nodes (LNs) in children and adolescents with papillary Thyroid Carcinoma (PTC).From December 2014 to March 2018, 10 metastatic LNs in 5 children and adolescents  with PTC treated by RFA were evaluated in this study. The mean number of surgical procedures performed before RFA was 1.2 (range 1-2) and the mean number of treated metastatic LNs per patient was 2 (rang 1-3). RFA was performed with an 18–gauge bipolar RF applicator under local anesthesia. Follow-up consisted of US and serum thyroglobulin (Tg) level at 1, 3, 6, 12 months and every 12 months thereafter.P = 0.005) with a mean VRR of 99.28 ± 2.27%. A total of 9 metastatic LNs (90.00%) completely disappeared. After RFA, 2 patients developed newly metastases. One patient had additional RFA. The other one with multiple LN metastases underwent total thyroidectomy with central neck dissection.All the patients were well tolerant to RFA procedure and no procedure-related complications occurred. During a mean follow-up time of 52.00 ± 21.44 months, the initial volume of LNs was 0.30 ± 0.38 ml, which significantly decreased to 0.01 ± 0.03 ml (As a less invasive and effective technique, RFA may provide another alternative to the existing therapeutic modalities for cervical metastatic LNs in children and adolescents with PTC. The pro therapy . Althoug therapy . For pat therapy . 131 I tgnancies . AccordiRadiofrequency ablation (RFA), as a minimally invasive treatment, has been used as an alternative to surgery for various solid tumors in adults –9. It haTherefore, the aim of this study was to evaluate the safety and efficacy of RFA for metastatic LNs in children and adolescents with PTC.The study was approved by the Institutional Review Board of Chinese PLA General Hospital. Written information consent was obtained from all the patients’ parents prior to RFA procedure.Between December 2014 to March 2018, 5 patients  with 10 metastatic LNs from PTC were treated by RFA in our institution. Inclusion criteria were: (1) age ≤ 20 years; (2) prior resection of primary tumor with pathological PTC confirmation; (3) patients with metastatic LNs confirmed by ≥ 2 separate fine-needle aspiration (FNA) or core needle biopsy (CNB); (4) the number of metastatic LNs was ≤ 3; (5) LNs deemed technically treatable based on US imaging and patient’s condition.US examinations before and after RFA, as well as during follow-up were performed using a Siemens Acuson Sequoia 512 Ultrasound System  with a 15L8W linear array transducer or a Philips iU22 Ultrasound System  with a L12-5 linear array transducer or a Mindray M9 Ultrasound System (Mindray) with a L12-4 linear array transducer.Before RFA, all the metastatic LNs were evaluated by US including the location, size, echogenicity, component and vascularity. For each metastatic LN, the diameters in three dimensions (the largest diameter and two perpendicular diameters) were recorded. The volume was calculated with the equations :V is the volume, while a is the largest diameter, b and c are the other two perpendicular diameters.All RFA procedures were performed by an experienced US physician with more than 20-year experience in thyroid US and interventional US. A bipolar RFA generator  and an 18–gauge bipolar RF applicator with 0.9 cm active tip was used  in this study. During the application of RF energy, the generator continuously measured the electric impedance of the tissue between the two electrodes at the tip of the RF applicator. The power was automatically adjusted based on the change of tissue impedance.via the antecubital vein. Before RFA, in order to design the best insertion way, US and CDFI were performed by the operator to evaluate the relationship between metastatic LNs and cervical critical structures such as trachea, vessels, esophagus and recurrent laryngeal nerves. Local anesthesia with 1% lidocaine was injected at the subcutaneous puncture site and the periphery of metastatic LNs. RFA was performed using hydrodissection technique. Normal saline was injected using another needle (23 gauge) to separate the metastatic LN from critical structures in order to prevent thermal injury. The RFA power was 3 W, if a transient hyperechoic zone did not form at the electrode tip within 5–10 s, the radiofrequency power was increased to 5-8 W. The ablation was terminated when all portions of the target ablation area had changed to transient hyperechoic zones.RFA was performed in outpatient department. Patients were supine with the neck extended during the procedure. An IV line was introduced During the procedure, we gave special attention to the preservation of critical cervical structures in order to prevent significant complications such as hematoma or nerve injury. After ablation, each patient was observed for 1–2 hours in the hospital while any complication occurring during and immediately after ablation was carefully evaluated according to the clinical signs and symptoms.Clinical follow-up consisted of US and serum thyroglobulin (Tg) levels at 1, 3, 6 and 12 months and every12 months thereafter. The ablated volume, the largest diameter, vascularity and the development of new metastatic tumors were evaluated during the follow-up. The percentage volume reduction ratio (VRR) was calculated as follows:Complications during follow-up were assessed using the reporting standards of the Society of Interventional Radiology , 21. TheP < 0.05 was considered as statistically significant.Statistical analysis was performed using the SPSS statistical software (Version 25.0). Continuous data was expressed as mean± SD (range). Changes of the mean volume and diameter were compared using Wilcoxon signed rank tests before RFA and at the last follow-up visit. A difference with 131 I therapy. The mean number of surgical procedures performed before RFA was 1.2. The mean interval time between initial surgery and RFA was 3.20 ± 1.64 years (range 2-6 years). The mean number of treated metastatic LNs per patient was 2. The locations of metastatic LNs were as followed: 2 at right level IV, 5 at left level III, 2 at left level IV and 1 at right level VI. The mean of largest diameter of metastatic LNs was 1.16 ± 0.52 cm. The mean initial volume was 0.30 ± 0.38 ml.Clinical characteristics of the 5 patients  before RFA are summarized in A power of 3W was used in 4 patients and 6W was used in 1 patient. The mean ablation time was 158.80 ± 65.13s (range 98-263s), and the mean energy was 522.00 ± 211.59 J (range 290-760J). All the patients were well tolerable the RFA procedure. None of the patients experienced any life-threatening or delayed complications related to RFA during the follow-up.P=0.005). The mean volume of the metastatic LNs decreased significantly from 0.30 ± 0.38 ml (range 0.06-1.23 ml) to 0.01 ± 0.03 ml (range 0-0.09ml) (P=0.005) with a mean VRR of 99.28 ± 2.27% (range 92.82-100%) (P=0.042).The outcomes of RFA for metastatic LNs in patients with PTC are summarized in 82-100%) 2. A totAfter RFA, there was no evidence of recurrence at the initial treatment location. A total of 2 patients developed newly metastases. Patient 3 had multiple LN metastases at 2 years after RFA. This patient underwent total thyroidectomy with central neck dissection. During the surgery, no adhesion with strap muscle by RFA was found. After histopathological examination, metastases were detected in 8 out of 10 resected LNs. Patient 4 had one newly metastatic LN  at right level IV at 15 months after RFA and underwent additional RFA. A power of 6W was used. The ablation time was 77s, and the energy was 390J. This newly metastatic LN was ablated successfully with no complications.This study is the first to demonstrate the efficacy and safety of RFA for cervical metastatic LNs in children and adolescents with PTC. Our study showed that after a mean follow-up time of 52.00 ± 21.44 months, the VRR of metastatic LNs was 99.28 ± 2.27% and 90.00% of the ablated LNs completely disappeared. After RFA, a total of two patients developed LN metastases. One patient underwent total thyroidectomy with central neck dissection and the other one chose additional RFA. All the patients were well tolerable the RFA procedure. No complications were encountered. These results showed that RFA might be effectively applied in children and adolescents without increasing technical difficulties by former surgery.131I therapy, which might reduce future recurrence risk but was unlikely to improve mortality , National Natural Science Foundation of China (No. 81771834), and the Research of Healthcare Big Data f Chinese PLA General Hospital (2019MBD-040).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In India, although incidence of Herpes zoster has not been assessed, regional cases have been reported. We revisited the peer-reviewed literature on clinical cases of HZ to depict the trends in population characteristics, disease presentation, and predisposing factors for the disease in India. Systematically conducted literature search yielded 27 studies, published between January 2011 and May 2020, reporting 3124 HZ clinical cases, with high proportions in older adults (>50 years of age: 15.0–81.3%). Thoracic dermatome was consistently reported as the most frequent site affected by HZ (38.9–71.0%). Post-herpetic neuralgia and secondary bacterial infections were the two most frequent complications . Despite the paucity of data and gaps in the reporting of HZ cases, available evidence indicate that the disease causes an important burden to older adults in India, suggesting that preventive strategies, along with recommendations to healthcare practitioners, can help mitigate the burden of HZ. What is the context?Herpes zoster is caused by reactivation of the varicella virus in sensory gangila usually during older age.The most common complication involve skin and neurological disorders, such as post herpetic neuralgia.Herpes zoster can impact quality of life for months or even years .In India, there is a lack of population-based studies on herpes zoster to reflect burden of disease.What is new?We reviewed the literature on clinical cases of herpes zoster in India from last decade and found that:High propotions of older adults (>50 years of age) are reported to have the disease.Thoracic dermatomes and post herpetic neuralgia are common clinical presentation and complication.Post herpetic neuralgia is observed more frequently in older patients.What is the impact?Our review highlights sigificant number of cases of herpes zoster are reported and the disease causes a substantial burden to older adults in India.In view of the growing elderly population in India, the finding of greater proportion of cases in >50 years of age holds importance.Implementation of preventive strategies along with guidance to healthcare pracitioners can help prevent the disease and complications in vulnerable population. The pain can be debilitating and lead to physical disability, emotional distress, and sleep disorder.5 Worldwide, estimates for the risk of PHN following HZ episode range between 5% and 30%.6 Herpes zoster ophthalmicus (HZO) is another presentation of the disease that can lead to ocular complications, often causing decreased visual acuity or even blindness.7HZ episodes may lead to complications and sequelae, including, neurological disorders like post-herpetic neuralgia (PHN), limb paralysis, cerebrovascular disorders like stroke, cardiovascular disease such as myocarditis, and serious skin alterations such as intense scarring.3 Pain is usually managed with analgesics but may require strong opioids.8 Antiviral agents such as acyclovir, famciclovir, and valaciclovir are commonly used in the treatment of the disease.8 Local management of skin lesions may help in alleviating the discomfort and preventing the development of long-lasting skin lesions. For patients suffering from PHN, treatment comprises anticonvulsants, tricyclic antidepressants, topical therapies, and opioids.9Treatment of acute HZ is primarily designed to manage pain, and hasten recovery.10 In Asia, the overall HZ incidence has been estimated at 5.0 per 1000 person-years (PY).4 Stratification by age groups yielded median values of 2.0–3.1, 4.3–5.2, and 7.4–13.8 per 1000 PY in the 0–20, 20–50 and in >50 years old populations, respectively.4 To the best of our knowledge, there are no population-based studies with potential to provide incidence data specific to India. While there is study-to-study variation due to differences in methodology, location appears to have little impact on the incidence of HZ, which is similar in different regions of the world.11–13Many studies have been conducted across different parts of the world to study the incidence rates of HZ.The aim of this work was to better understand the clinical profile of HZ disease reported in India. To achieve this, literature was collected through searches carried out systematically in the PubMed and Embase databases for the period of Jan 2011 to May 2020. An additional search was performed in Google Scholar which is described in the literature search section. We have described the trends in demographic characteristics of HZ patients, clinical presentation of the disease, complications and predisposing factors reported in Indian studies published between 2011 and 2020.th and 26th, 2020 in PubMed and Embase, respectively. An additional search was performed in Google Scholar for “study” and “herpes zoster”  on January 8th, 2021 to identify additional literature not indexed in PubMed nor Embase. Screening of titles, abstracts, and full texts was performed by two independent reviewers. Any discordance about the final selection of articles was collegially resolved according to the pre-specified inclusion/exclusion criteria. Data were collated for descriptive purpose.Research articles in English language published since 2011 were searched for “zoster” and “India” in all fields on May 20Articles reporting analytical, prospective observational, cross sectional, retrospective reviews, and time bound studies conducted in either dermatology, medicine and/or ophthalmology departments of various medical colleges and tertiary care centers across India were included. Only studies reporting data from multiple HZ patients, providing quantitative data about demographics, various disease presentations, complications or risk factors in India were selected.Individual case reports, case series not providing quantitative analysis, scholar theses, editorials and letters to editors were excluded from the review. Articles reporting interim analyses of studies for which the final analysis was already included were excluded from the review to avoid inclusion of redundant datasets. Articles published before 2011 and after May 2020 were excluded from the Google scholar search to match the settings of the Embase and PubMed searches.14–27 A search for additional literature in Google Scholar, was carried out due to limited number of articles retrieved in the initial search. Post Google scholar search, 13 additional articles were further added.28–40 Also the 2013 paper from Nithyanandam et al.25 was a post-hoc analysis, so we retrieved the data from the primary publication.41 Data were extracted from the 27 relevant articles for review.There were 242 and 528 records retrieved from PubMed and Embase respectively . After elimination of 163 duplicate records, titles and abstracts of 607 unique records were screened. A total of 14 articles were included from this initial search.A total of 27 studies collectively reporting 3124 HZ patients (range 18 to 938) conducted between 2003 and 2019 were retrieved. Location and period of these studies along with demographic characteristics of the HZ patients are reported in 33 Eight studies reported exclusively on HZO cases.41Of the retrieved studies, 24 were prospective cross-sectional and three were retrospective (Supplementary Table 1). Nine studies either did not mention or failed to report the study period. Clinical diagnosis and Tzanck smear tests were mostly used as case definition for HZ, though this information was not systematically reported. Most studies (n = 21) included patients of all ages, while four studies reported HZ cases in the pediatric population only.40 provided proportions of HZ cases among all patients who attended outpatient visits in the considered departments, ranging between 0.28 and 2.36% , conducted between 2008 and 2016 in rural Gujarat, 25.5% of the cases occurred in individuals older than 60 years.31As seen in Supplementary Table 1, eleven studies that included patients of all ages reported their mean age ranging between 29.6 and 57.3 years.41 Six studies found the ratios to be in the order of 2:1,40 Five studies, however, reported more women patients with HZ than men, in the range of 0.6:1 to 0.9:1.39Male:female ratio ranged between 1.1:1 and 1.9:1 in 15 studies .14,16,1933 Proportion of patients who had chickenpox ranged between 22.7%31 and 79.6% (Supplementary Table 1).28 Varicella vaccination history was documented in only four studies,33 and proportions were in the range of 0.0%33 to 30.8%21 of cases.Eleven studies reported the proportion of HZ patients with a known history of varicella infection (chickenpox).34–41 For other studies, HIV status was either not assessed or mentioned. The reported frequency of HIV seropositivity among the studied patients varied between 0%38 and 44.4%.17 Diabetes mellitus was reported in 15 studies34–39 with a percentage range of 0%27 to 56.3%.35 The highest proportion of diabetes (56.3%) was reported in a study conducted in the Ophthalmology department of a tertiary hospital in Odisha where 20/32 patients (62.5%) were older than 60 years of age.35Besides advanced age, human immunodeficiency virus (HIV) seropositivity, diabetes mellitus, prolonged steroid use, and malignancies with therapy were the frequently associated predisposing/co-morbid conditions in the retrieved studies (Supplementary Table 1). HIV status of the enrolled population was clearly stated in 23 studies.27 and 44.4%.17 However, given the high uncertainty of the data and possible selection bias, data on immunocompromised population should be interpreted with caution.Immunocompetence level is not assessed or clearly reported in all studies. Moreover, some authors considered diabetes as an immunocompromising condition while others did not. According to authors’ assessments, proportion of immunocompromised patients varied between 0%41 Reported prodromal symptoms included segmental pain (58.9%–100%),39 fever (2.5%–44.4%),31 headache (3.4%–10.0%),31 itching (8.0%–45.5%),28 burning sensation (13.3%–68.9%),34 and paresthesia (6.2%–50.0%).28 In studies focused on HZO patients,41 the reported prodromal symptoms were eye watering (33.3%–58.9%),37 lid swelling (18.5%–87.5%),35 and diminution of vision (25.0%–37.0%).38Twenty studies described the prodromal symptoms experienced by the patients (Supplementary Table 1).39 Other commonly affected sites were the cranial (3.3%–28.3%),28 cervical (4.0%–23.8%),36 and lumbar (5.5%–35.0%) regions.33 Three studies reported cases of multi-dermatomal involvement.36 Sharma and Sharma observed multi-dermatomal presentation in 8.25% of the 109 reported cases.29 Among the 100 patients reported by Usha et al., 42% had multi-dermatomal involvement, among which 87.5% were living with HIV.36 Vora et al. noticed that among 938 HZ patients, 43 cases (4.6%) had multiple dermatomes involved.31Eighteen studies reported dermatomal distribution as per site/location in HZ patients . Thoraci41 Pain preceded vesicles onset in 60.4% of the patients recruited in Karnataka by Malkud et al.20 In the same study, 15 out of 240 patients (6.3%) experienced intermittent radicular pain and 10 patients (4.2%) suffered continuous pain.20Pain was a common symptom in many studies.31 Burning pain (18.3%) and pricking pain (54.2%) were also described in the study by Rachana et al. on 72 HZ patients.39 Burning pain was also denoted as a common finding in the three studies reported by Adhicari and Agarwal, Gupta and Sareen, and Mitra et al.37In the study by Vora et al., burning pain affected 720/938 HZ patients (76.8%), which was by far the most common type of pain encountered; other types of pain were itching pain (8.0%), pricking pain (7.4%) and throbbing pain (5.2%).41 PHN (10.2%-54.7%)41 and secondary bacterial infections (3.5%–21.0%)36 were the most frequently reported complications. Other complications included scarring (including keloids),36 paresthesia with motor involvement,30 sensory and hearing loss,41 Ramsay Hunt syndrome,30 and pigmentary changes.36 Among HZO patients, corneal lesions were common.41 HZO patients also suffered a wide range of complications including visual impairment,41 and secondary glaucoma (detailed in Supplementary Table 1).38Among the retrieved studies, 21 publications provided data on associated complications (Supplementary Table 1).41 and its incidence was found to be higher among the older individuals (>50 years old) in the study of Puri.26 Also, as per Adhicari et al., maximum cases of PHN were concentrated in the age group 41–70 years old.28 Similarly, Malkud et al.20 reported that overall proportion of PHN among the 240 HZ patients was 10.4%, and that half of HZ patients 60 years or older developed this complication.20PHN accounted for 10.2% to 54.7% of the reported complication among HZ patients (Supplementary Table 1),17 proportion of PHN was higher among patients living with HIV (n = 6/8: 75%) when compared to the rest of HZ patients (n = 1/10: 10.0%). Usha et al. also reported a greater proportion of PHN cases in HIV seropositive patients (n = 8/32: 25%) relative to HIV seronegative patients (n = 7/68: 12.9%).36PHN was also observed with higher frequency in immunocompromised patients. In a study conducted by Gupta et al.,41 Acute corneal epithelial lesions (64.1%), reduced corneal sensation (67.2%) and uveitis (48.4%) were some of the serious complications reported in a study of 64 patients.41 In another study (n = 25 HZO patients), 76.0% suffered lid edema while 52% had decreased corneal sensitivity.23 Also, impaired visual acuity was reported in 40% of the patients in the same study.23 Lid (52.6%) and corneal (56.6%) involvement, along with PHN (30.9%) were also reported in a retrospective study (n = 249 HZO cases) between 2006 and 2016 in two tertiary referral eye centers.16 Anterior uveitis was the most frequent presenting symptom (>50% of cases) seen.16 In a separate study of 18 HZO, 83.3% of the patients manifested corneal involvement.17 In the same study it was mentioned that visual acuity was better in patients with HIV-negative status than in those living with HIV.HZO, the form of HZ affecting the first branch of the trigeminal nerve, i.e. the ophthalmic nerve, may include additional ocular symptoms and complications. Eight studies specifically described HZO and its associated complications in detail (Supplementary Table 1).This is the first large scale review of the published literature to ascertain the occurrence of HZ and its complications in India, as well as gaps in available data about the disease in India. Acknowledging the fact that HZ is not notifiable and in the absence of population-based epidemiological studies, along with poor surveillance system, it is important to fall back on a literature review. Though studies in various outpatient settings of tertiary care centers differ in terms of design, methodology and other various aspects, the data are of significance as it gives a fair estimate of the course of disease, its characteristics, and complications. Nonetheless, possible recruitment bias and gaps in data regarding patients’ characteristics, disease presentation, as well as complication in the retrieved literature, impaired us from performing quantitative analyses and may be responsible for the differences in proportions of HZ in older adults, as well as rates of complications, PHN and bacterial infections.22 and 2.36%.27 The proportions differ among studies mainly due to differences in characteristics of the population evaluated. Despite this fact, the pattern is similar to that reported in Asia-Pacific region .4 This tends to indicate that proportion of HZ in India is similar to rates reported elsewhere.4 However, HZ proportions seen in this review are likely to be underestimated, mainly due to factors such as community and patient seeking behavior, physician practice, HZ severity, etc. It was moreover observed that HZ incidence rates are increasing in countries across Asia-Pacific ,42 which is most likely attributable to rising incidence in aging populations.4 Similarly, a growing number of HZ cases is expected to occur in India in the coming years as the Indian population aged 50 years and above has quadrupled over the last years, and is expected to comprise 404 million people in 2036, representing 27% of the country’s projected population.44 Indeed, while HZ cases were reported across age groups, it was predominant in individuals >50 years of age (15.0–81.3%). This is in agreement with the literature where the age-related increased incidence of HZ is thought to result from the decline in cell-mediated immunity (immunosenescence).13 Besides advanced age, patients affected by chronic diseases are also fragile due to impairment of cell-mediated immunity.45–47 Accordingly, HIV, diabetes mellitus, malignancies, and other chronic conditions were the frequently reported ailments in patients with HZ. It is noteworthy that India had an epidemic peak of HIV around 2000 and that the prevalence trend is now declining, reaching 0.22% among adults aged 15 to 49 years in 2019.48This review notably indicates that the risk of HZ is significant in individuals older than 50 years of age, as observed in studies conducted in other parts of the world, and that HZ cases are seen by a variety of medical specialists , depending on disease presentation. Proportions of HZ patients among patients with other conditions at dermatology outpatient departments, was between 0.28%41 of the patients accounted with PHN. Though the risk of PHN may vary by study design, age or definitions used for PHN, the proportion was in accordance with the reported numbers (5% to >30%), including studies from North and South America, Europe, the Middle East, as well as the Asia-Pacific region.49 The incidence of PHN was found to be higher among the older (>50 years old) HZ patients, in agreement with the reported increase in frequency and severity of PHN with advancing age.50 The pain and discomfort associated with PHN can be prolonged and disabling, diminishing the patient’s quality of life and ability to function.51PHN is the most common complication of HZ. In present review, 10.2% to 54.7%52 HZO and ocular complications were also reported in studies included in present review. As per peer-reviewed literature, wide range of eye complications, such as keratitis, uveitis and conjunctivitis have been reported in the range of 30% to 78%.6HZO is another relatively common presentation of HZ with a reported incidence of 10–15% of all herpes zoster cases.In India, HZ is not a reportable disease and despite poor surveillance system, a good number of clinical cases were reported in this review. Also, in view of the growing elderly population in India, the finding of greater proportion of cases in >50 years of age holds importance. The evidence generated needs be further strengthened and one way would be to conduct nationwide population-based study that is critical to investigate the true burden and epidemiology of HZ disease in India. However, until that time, as HZ cases are seen by a variety of medical specialists and the disease can cause substantial morbidity among older adults, prevention strategies and recommendations or guidance from healthcare professionals (HCPs) can play a critical role.Click here for additional data file.Click here for additional data file.


To investigate whether the reproductive outcomes of oocytes with smooth endoplasmic reticulum aggregates (SERa) are impaired.A total of 2893 intracytoplasmic sperm injection (ICSI) cycles were performed between January 2010 and December 2019 in our center. In 43 transfer cycles, transferred embryos were totally derived from SERa+ oocytes. Each of the 43 cycles was matched with a separate control subject from SERa- patient of the same age ( ± 1 year), embryo condition, main causes of infertility, type of protocols used for fresh or frozen embryo transfer cycles. The clinical pregnancy, implantation, ectopic pregnancy and live birth rate were compared between the two groups.vs. 65.11%, p=0.5081), implantation rate  and live birth rate  between the SERa+ oocyte group and the matched group. No congenital birth defects were found in the two groups.43 embryo transfer cycles from SERa- patient were matched to the 43 transferred cycles with pure SERa+ oocytes derived embryos. No significant difference was observed in clinical pregnancy rate (55.81% Our results suggest that the implantation, clinical pregnancy, live birth and birth defects rate of embryos derived from oocytes with SERa are not impaired. Aggregates of smooth endoplasmic reticulum (SERa) in the ooplasm is one of the cytoplasmic dysmorphisms of oocytes. These aggregations appear as round flat disks in the ooplasm corresponding to large tubular SER clusters surrounded by mitochondria .Otsuki et al. firstly reported significantly lower pregnancy rates in SERa+ cycles and the transfer of embryos derived from SERa+ cycles resulted in Beckwith-Wiedmann syndrome . SubsequAfter the consensus was published, more research focused on this field. However, the conclusions are inconsistent. The clinical pregnancy rate was comparable between SERa+ and SERa− cycles in the most of the published studies , 3, 6–13However, most of the published literatures compared the clinical pregnancy outcomes between SERa+ and SERa− cycles , 16, 17.Therefore, in order to clarify whether SERa have adverse effects on reproductive outcomes, direct comparison should be made between embryos derived from SERa+ oocytes in SERa+ cycles and embryos from SERa- cycles. Furthermore, it should be acknowledged that these studies are fraught with potential biases and confounders. Factors, such as maternal age, embryo conditions, main causes of infertility, type of protocol etc., were not matched in these studies, which could lead to inaccurate conclusions.In this report, we conducted a matched, case-control study to determine whether the embryos derived from SERa+ oocytes were associated with negative reproductive outcomes.All women undergoing intracytoplasmic sperm injection (ICSI) cycles that did not involve pre-implantation genetic testing (PGT) in the Centre for Reproductive Medicine, Guangzhou Women and Children’s Hospital between January 2010 and December 2019 were included in the study. Since the presence of SERa cannot be observed on the day of insemination, patients undergoing conventional IVF and split IVF-ICSI were excluded from the study. The study was approved by the Independent Ethics Committee of Guangzhou Women and Children’s Hospital.SERa+ oocytes were defined as those oocytes where one or more SERa were visible with an inverted microscope after denudation just prior to ICSI. A SERa+ cycle indicates that at least one SERa+ oocyte is observed among the cohort. The SERa- cycles had morphologically normal oocytes. When all the cycles are SERa-, the patient is defined as a SERa- patient.Both fresh and frozen embryo transfer (ET) cycles were included in the study. The reproductive outcomes were only analyzed in transfer cycles where transferred embryos were totally derived from SERa+ oocytes.Standard controlled ovarian stimulation protocols were used. Briefly, the patients underwent either GnRH agonist or GnRH antagonist protocol for ovulation induction. The ovarian stimulation was performed using recombinant FSH  in combination with GnRH antagonist  or agonist . The initial doses were based on antral follicle counts, female age, and basal FSH. The subsequent doses were adjusted according to follicle growth and serum estradiol levels. HCG or GnRH agonist was administered when at least three leading follicles reached a mean diameter ≥ 18 mm. Transvaginal oocyte retrieval was scheduled 34–38 h later.2, 37°C until days three. Embryos with extended culture were transferred on day three to G2  media and cultured individually under the same conditions until day five or six. Cleavage stage embryos were assessed for cell stage, percent fragmentation, multinucleation, and blastomere symmetry according to ESHRE/ALPHA consensus . The embryo transfers were done with ultrasound guidance by using a standard embryo transfer catheter .In 43 transfer cycles, including 13 fresh transfer cycles and 30 frozen transfer cycles, the transferred embryos were totally derived from SERa+ oocytes. The matched group was drawn from all ICSI cycles from SERa- patients. Matching was accomplished by the following criteria: [1] age( ± 1 year); [2] embryo condition  [3] main causes of infertility ; [4] type of protocol used for controlled ovarian hyperstimulation (COH) in fresh embryo transfer or endometrium preparation protocol in frozen embryo transfer; [5] infertile years ( ± 2 year); [6] number of transfer cycles; [7] embryo transfer date ( ± 1 year); [8] embryo transfer physician. We required exact matching for criteria 1–4; for criteria 5–8, we attempted matching as closely as possible and in most cases were able to match at least two of these criteria. To reduce the introduction of potential bias, researchers were blinded to reproductive outcomes during the matching process. If multiple patients fit the criteria, one was chosen at random.The implantation rate was calculated as the number of gestational sacs divided by the number of transferred embryos. Clinical pregnancy was defined as the presence of an intrauterine gestational sac with a yolk sac, a fetal pole, and fetal heart pulsations. Ectopic pregnancies were diagnosed by ultrasound or by laparoscopic visualization of an extrauterine gestational sac or by the absence of an intrauterine gestational sac and increasing β-hCG levels following the failure of suction D&C to reveal products of conception. Live birth was defined as the birth of a live infant at ≥28 weeks of gestation.P value <0.05 was considered statistically significant.Data are presented as the mean ± standard deviation. Statistical comparisons of 2 experimental groups were evaluated by 2-tailed Student t test if data distribution passed the normality test. The Mann-Whitney U test was used for comparison if data distribution failed the normality test. A chi-square test or Fisher’s exact test to compare fertilization, pregnancy and live birth rate etc. vs. 21.6 ± 3.0), stimulation protocols and total gonadotrophins dose (2090.7 ± 918.7 vs. 2043.8 ± 943.9) between the two groups. Compared with SERa-cycles, significant younger age (33.5 ± 5.4 vs. 34.5 ± 5.6), more stimulation days (9.3 ± 2.5 vs. 8.9 ± 2.8), higher estradiol levels at hCG-trigger (9973.3 ± 5403.3 vs. 8662.2 ± 5477.4), and more mean number of retrieved oocytes (11.5 ± 7.9 vs. 8.8 ± 7.1) and MII oocytes (9.9 ± 6.7 vs. 7.4 ± 5.8) were found in SERa+ cycles.A total of 2893 ICSI cycles were performed between January 2010 and December 2019 in our center. Among them, 482 were SERa+ cycles, the incidence rate was 16.7%. The baseline characteristics, stimulation protocols and outcomes of SERa+ cycles and SERa- cycles are shown in In the 482 SERa+ cycles, 43 embryo transfer cycles were exclusively derived from SERa+ oocytes, including 13 fresh transfer cycles and 30 frozen transfer cycles. Totally 71 embryos, including 39 good quality embryos, were transferred. 43 embryo transfer cycles from SERa- patients were matched to the pure SERa+ oocyte group (1:1).vs. 86.05%), cleavage rate (99.09% vs. 97.80%) and D3 good embryo quality rate (33.84% vs. 32.69%) were all comparable between SER+ oocyte group and the matched group. vs. 65.11%), implantation rate (47.89% vs. 50.70%), ectopic pregnancy rate (4.17% vs. 0%), miscarriage rate (8.33% vs. 14.29%), live birth rate (48.84% vs. 55.81%), gestational week at birth (37.9 ± 1.7 vs. 37.8 ± 1.8), or birth weight (2.9 ± 0.6 vs. 2.8 ± 0.6) between the SERa+ oocyte group and the matched group. From these 43 transfers in SERa+ oocyte group, 21 live births were obtained and resulted in the birth of 28 healthy infants (7 twin pregnancy). No congenital anomalies were found in the two groups.The cycle characteristics of pure SERa+ oocyte group and matched group are presented in The occurrence rates of SERa reported in previous researches are different, ranging from 5.4% to 23.1% . ConsistSince Otsuki et al. firstly reported significantly lower pregnancy rate and fetal anomalies derived from SERa+ oocytes , more anTransfer of embryos originating from SERa+ oocytes was not avoided in our center. Previous investigation also showed that only 14% of centers discarded SERa+ oocytes and 43% of centers that did not discard oocytes followed up neonatal data  according to our embryo scoring criteria. This may explain the high pregnancy rate (55.81%) and live birth rate (48.84%) in our SERa+ oocyte group. 21 out of the 43 transfer cycles had alternative embryos, but embryo scoring was better in the SERa+ oocytes derived embryos. In the left 22 cycles in which no alternative embryos existed, the mean age (34.9 ± 7.0) was older, mean number of retrieved oocytes (7.0 ± 5.8) was relatively small. The acceptable clinical pregnancy rate (45.5%) and live birth rate (36.4%) in the 22 aged cycles also indicated that the clinical outcomes of SERa+ embryos are not impacted when there is no other alternative in embryo selection.To minimize the impact of the clinical heterogeneity observed between patients, we used multiple matching criteria. We attempted in particular to match for age, embryo condition, main causes of infertility, type of protocol used for COH in fresh embryo transfer or endometrium prepare protocol in frozen embryo transfer, which are known to affect IVF success. In our study, 43 transfer cycles with pure SERa+ oocyte derived embryos were included and compared with matched controls. This suggests that SERa+ oocytes are not associated with both decreased clinical pregnancy rate, implantation rate, gestational week, birth weight, live birth rate, and increased miscarriage rate and birth defect rate.As we mention above, if the presence of SERa in the cytoplasm of oocytes has a negative impact on clinical and neonatal outcome, the reproductive outcomes of the SERa+ embryo transfer cycle are most likely to be affected. After finding that the reproductive outcomes of SERa+ embryos were totally normal, we decided not to continue other subgroup analysis.Gurunath et al. reported that a gradual reduction in live birth rates was observed when the percentage of oocytes containing SERa increased and the group containing >50% of oocytes with SERa demonstrated no live births . HoweverWhether SERa increase birth defects has always attracted extensive attention. Based on previously reported cases of Beckwith-Wiedemann syndrome , diaphraSome limitations of our research should be noted. The nature of SERa makes it a retrospective study, which by nature cannot exclude selection bias. Furthermore, SERa can be classified on the basis of its size: large, medium and small aggregates . In mostThe implantation, clinical pregnancy, live birth and birth defects rate of embryos derived from oocytes with SERa are not impaired.The datasets generated for this study are available on request to the corresponding author. Requests to access the datasets should be directed to LS, sunling6299@163.com.The studies involving human participants were reviewed and approved by Independent Ethics Committee of Guangzhou Women and Children’s Hospital. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.LS was responsible for the conception and design of the study, interpretation of data, revised the article critically for important intellectual content, and approved the final draft for publication. JX and LY contributed to collect the data, analysis and interpretation of data; draft and revise the whole article. Z-HC, M-NY, and JC contributed to collecting the data, drafting and revising the article for important intellectual content. All authors contributed to the article and approved the submitted version.This study is supported by the National Natural Science Foundation of China (81800110).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.