Osteoarthritis (OA) is estimated to be the fourth leading cause of disability in the general population. It probably is the most common disease of joints in adults throughout the world. Knee OA accounts for more than 80% of the disease’s total burden and as per an estimate in US population, it affects at least 19% of adults aged 45 years and older. This was a randomised study aimed to evaluate the efficacy of platelet rich plasma (PRP) as a treatment modality for osteoarthritis knee in comparison to arthroscopic management.This study was conducted from 2018 to 2020 at a tertiary care teaching hospital, under reference number ELMC&H/RCELL2019/39. A total of 70 patients of osteoarthritis knee with grade 2-3 according to the Kellgren-Lawrence classification were selected using computer generated random number among them 35 patients were subjected to arthroscopy (Group II) and 35 were administered platelet rich plasma injection (Group I) and evaluated at 3, 6 and 9 months of follow-up. Both the groups were assessed and scored with the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Visual Analog Pain Scale (VAS) to compare pre-treatment and post-treatment values. As all the patients in the sample was followed-up, resulting into no loss of subjects.Overall, percentage reduction in VAS score at 3 months, 6 months, and 9 months was 24.45±9.09, 18.45±11.60 and 8.29±14.19%, respectively in Group I and 18.96±5.85, 7.33±8.60 and 3.20±7.39%, respectively in Group II. A statistically significant difference between two groups was observed at 3- and 6-months’ time intervals only (p<0.05). Overall, percentage reduction in WOMAC score at 3 months, 6 months and 9 months was 24.03±11.41, 17.45±9.24, and 9.49±9.80%, respectively in Group I and 11.27±5.73, 5.70±4.78, and -0.13±5.06%, respectively in Group II. At all the three-time intervals, the difference between two groups was significant statistically (p<0.001).This study suggested that both PRP as well as arthroscopy provide a reduction in WOMAC and VAS scores for pain among cases of knee osteoarthritis. Most effective reduction is observed at three months follow-up which thereafter tends to diminish. Of the two modalities, PRP seemed to have an edge over arthroscopic debridement, however, this efficacy was more pronounced for Kellgren-Lawrence Grade 2 as compared to Grade 3. It perhaps happens to be the most common disease of joints in adults across the world2. Among different types of OA, Knee OA is the most common comprising nearly 80% of the OA burden3. As per an estimate it affects at least 19% of adults aged 45 years and older in the US4. Increase in life expectancy leading to increase in proportion of elderly population coupled with lifestyle changes, osteoarthritis prevalence is increasing substantially with its prevalence being doubled since the mid-20th century5. Osteoarthritis of the knee has great physical and economic impacts. The disease usually evolves with increasing levels of pain, mobility restriction, and physical disability6. Most of the patients have no option but to undergo joint replacement surgery which again is an option not without risk and limitations. Therefore, there is need for a treatment option which could avoid or delay joint replacement and make patient comfortable till surgery becomes an absolute indication. A more generic approach to current treatment methods revolves around some combination of non-pharmacological and pharmacological treatment modalities7. Pharmacological treatment modalities such as steroids are often associated with side effects and in the early stages of disease, physiotherapy is the preferred approach for treatment and management. On the other hand, surgical modalities such as arthroscopy involves lavage  and debridement (to smooth the articular surfaces). In order to evolve a successful treatment modality for knee osteoarthritis it is essential to understand the etiopathogenesis of this disease. To cope up with this degeneration it is essential that the degeneration of cartilage should either be prevented or should be compensated with adequate regeneration. That is where the role of regenerative medicine comes into picture. Regenerative medicine helps to “replace, engineer or regenerate human cells, tissues or organs in order to restore or establish the normal function”.Osteoarthritis (OA) is recognised as the fourth leading reason for disabilityThe platelet augmentation revolves around the concept that platelet via an intricate vesicular storage system contain critical growth factors and mediators of tissue repair pathways. As a result of tissue injury, platelet receptors are triggered through a complex interaction of cellular and non-cellular signals which in turn lead to expulsion of these growth factors from within the site of injury through the process called as degranulation. It triggers cell proliferation and subsequently leads to tissue repair response. In recent years, a preparation called Platelet rich plasma (PRP) is an emerging treatment modality classified as “Orthobiologics”. PRP is a mix of autologous blood growth factors occurring naturally and is being used in different fields of medicine owing to its ability to accelerate tissue regeneration. Alfa granules in platelets contain numerous growth factors that enhance tissue recovery dramatically by catalysing the body’s natural healing response, tissue repair processes and induce the production of new collagen by the fibroblasts, osteoblasts and chondrocytes as per need of the parent tissue. In this backdrop, we carried out this study to assess the efficacy of platelet rich plasma (PRP) as a treatment modality for osteoarthritis knee as compared to arthroscopic management.Clearance for carrying out the study was obtained from the Institutional Ethical Committee before starting the study. The present study was carried out as a randomised controlled clinical trial at a tertiary care centre with state-of-the-art infrastructure catering primarily to socio-economically underprivileged suburban and rural population of northern India from 2018-2020 on 70 patients. Inclusion criteria for our study were: (a) Kellgren and Lawrence grade 2 and 3, (b) Age range 40 to 60 years, (c) Failed trial of conservative treatment not more than 6 months. The exclusion criteria were: (a) Inflammatory and Crystal Arthropathies, (b) Haematological diseases, (c) Patient who had injection of hyaluronic acid or steroid in last six months, (d) Active infection, (e) Patient not willing to consent for same. Sample size is calculated on the basis of post treatment variation at 12 months in WOMAC in the two groups using the formula:Where Σ1 = 19.69Σ2 =14.91 the SD of WOMAC of two group at 12 monthsType I error α = 5%Type II error β = 20% for 80% power of study.Data loss = 20%The sample size comes out to be 35 in each group. Only those providing consent to participate in the study were enrolled in the study. Patient were allocated to two groups using computer generated random numbers. Group I were administered Intra-articular injection of PRP (n=35), and Group II were subjected to arthroscopy (n=35) study is carried out as per flow chart .8.In Group I, the PRP required for injection was prepared and provided by the Department of Pathology ELMC&H Lucknow (UP), India. About 20cc of whole blood was withdrawn under aseptic precautions atraumatically from antecubital vein, this whole blood mixed with 2.8ml of Acid Citrate Dextrose solution (ACD solution) in sterile vials, because ACD beside acting as an anticoagulant also maintains the intra platelet signal transduction mechanism during PRP preparation and thus improves overall responsiveness of platelets 9. The final product 4ml - 5ml of PRP was injected in knee by aseptic technique without prior activation by mean of pharmacological agents as PRP presents higher percentage of activated platelets. Platelets counts was done by automated machines in whole blood and in PRP. In humans, the typical baseline blood platelets count is approximately 150,000/μL - 350,000/μL while in PRP, concentration of platelets should increase 3 - 5 times than that in whole blood for proper effect. The mean platelet count in the whole blood was 241,000/μL and mean platelet count in the PRP was 1,019,000/μL. After taking informed and written consent, patient was shifted to minor O.T. Patient was placed in supine position with knee in full extension. Under aseptic condition, 4ml - 5ml of PRP was injected in knee through supralateral approach with a 22-gauge needle without local anaesthesia. Knee immobilised for 8-10min and discharged after half an hour of observation. Tablet paracetamol (650mg) was given stat in patients who experienced pain at injection site after 10min. All patients were asked to stop medications 48hrs before follow-up assessment.The tubes were then centrifuged using Remi 8c centrifuge model for 15min at 1500rpm on a table top centrifuge and the blood was separated into PRP and residual red blood cells with the Buffy coat. The PRP was then extracted through a pipette and transferred to a test tube. After waiting for one hour at 20° - 22° (air-conditioned room) so that platelets come in resting phase In Group II, the patient was clinically examined and prepared for arthroscopy by anaesthetic staff. Suitable anaesthesia was provided after obtaining an informed consent. Patient was moved to Orthopaedic Operating theatre. A small incision called portals in the knee was made to insert the arthroscope. Several other incisions were required to see other parts of the joint or to insert other instruments. These incisions were small enough to be closed with one or two stitches, or with narrow strips of sterile adhesive tape. An arthroscopic awl was used to make micro fractures in the subchondral bone till fresh subchondral bleeding occurred. In Debridement procedure damaged portions of articular cartilage, meniscus, synovial membrane or ligaments found within the joint were excised. The joint was visualised and irrigated with normal saline or lactated ringer’s solution. Patient was shifted to recovery room for a few hours.Patient was prescribed medication to relieve pain and inflammation. Patient was advised to take rest, compress, and elevate the joint for several days to reduce swelling and pain and if required use splints, slings or crutches. Patient was advised to immediately inform if any complications like fever, pain not helped by medication, drainage from incision site, redness or swelling, new numbness or tingling was encountered.In both the groups, pre-operative pain was assessed using the VAS with the patient performing five active tests: (a) straight leg raising, (b) knee flexion with the patient lying supine, (c) knee extension with the patient sitting on the couch, (d) knee flexion with the patient sitting on the couch, and (e) five steps walking.Scoring system were used to assess the post treatment condition of patient before intervention and at follow-ups at three, six and nine months. The scoring system were: (a) Visual Analog score (VAS) for Knee pain, (b) The Western Ontario and McMaster Universities Arthritis Index (WOMAC). WOMAC index is a self-administered questionnaire consisting of 24 items divided into three subscales: Pain (5 items), Stiffness (2 items), Physical Function (17 items).The statistical analysis was done using SPSS [Statistical Package for Social Sciences] Version 21.0 statistical Analysis Software. The values were represented in Number (%) and Mean±SD.The present study was conducted in the Department of Orthopaedics, Era’s Lucknow Medical College and Hospital to compare the clinical results of application of Arthroscopy versus Intraarticular platelet rich plasma injection in patients of osteoarthritis of knee. A total of 70 cases of osteoarthritis scheduled management fulfilling the inclusion criteria and giving consent for inclusion in the study were enrolled. These patients were randomly allocated to two equal groups by computer generated random number technique. Patients were distributed in two groups as Group 1 (n=35) and Group 2 (n=35). Following table shows comparison of general profile and disease characteristics of patients of above two groups At the time of enrolment, out of 70 patients 33 (47.1%) were assessed as KL Grade 2 and rest 37 (52.9%) as KL Grade 3. Though proportion of KL Grade 2 patients was higher in Group I (54.3% vs. 40.0%) but this difference was not found to be significant statistically .Pre-intervention WOMAC score of KL Grade 2, KL Grade 3 and overall patients of above two groups were found to be comparable . Pre-intAt all the follow-up periods  VAS score of patients of Group II was found to be higher as compared to Group I (irrespective of KL Grade). Difference in VAS score between above two groups were not found to be significant at 3 months among KL Grade 3 cases, and at 9 months when evaluated separately for KL Grade 2 and Grade 3, but significant differences were found for overall patients at follow-up at 9 months .Overall, percentage reduction in WOMAC score at 3 months, 6 months and 9 months was 24.03±11.41, 17.45±9.24, and 9.49±9.80%, respectively in Group I and 11.27±5.73, 5.70±4.78, and -0.13±5.06%, respectively in Group II. At all the three-time intervals, the difference between two groups was statistically significant (p<0.001). Among KL2 grade patients, percentage reduction in WOMAC score at three months, six months, nine months was 31.59±6.61, 23.11±5.60, and 15.20±5.60%, respectively in Group I and 12.78±5.56, 6.24±4.80 and 1.14±5.14%, respectively in Group II. At all the three-time intervals, the difference between two groups was significant statistically (p<0.001). Among KL3 grade patients, percentage reduction in WOMAC score at 3 months, 6 months and 9 months was 15.05±9.17, 10.72±8.19, and 2.71±9.45%, respectively in Group I and 10.26±5.75, 5.34±4.85, and -0.97±4.95%, respectively in Group II. A significant difference between two groups was observed at 6 months follow-up only (p=0.017) .Overall, percentage reduction in VAS score at 3 months, 6 months and 9 months was 24.45±9.09, 18.45±11.60, and 8.29±14.19%, respectively in Group I and 18.96±5.85, 7.33±8.60, and 3.20±7.39%, respectively in Group II. A statistically significant difference between two groups was observed at three- and six-months’ time intervals only (p<0.05). At nine months, though percentage reduction was higher in Group I as compared to that in Group II, yet this difference was not statistically significant (p=0.064). In KL Grade 2 patients, percentage reduction in VAS score at 3 months, 6 months and 9 months was 28.87±8.24, 19.70±5.14, and 7.24±8.81%, respectively in Group I and 20.86±6.02, 8.12±10.50, and 4.76±9.65%, respectively in Group II. A statistically significant difference between two groups was observed at 3- and 6-months’ time intervals only (p<0.05). At 9 months, though percentage reduction was higher in Group I as compared to that in Group II, yet this difference was not statistically significant (p=0.448). Among KL Grade 3 patients, percentage reduction in VAS score at 3 months, 6 months and 9 months was 19.20±7.19, 16.96±17.40 and 9.52±18.99%, respectively in Group I and 17.69±5.51, 6.80±7.31, and 2.15±5.42%, respectively in Group II. A statistically significant difference between two groups was observed at 6 months’ time interval only (p=0.016). At 3 months and 9 months, though percentage reduction was higher in Group I as compared to that in Group II, yet this difference was not significant statistically (p>0.05) .We conducted a randomised controlled trial in which a total of 70 patients with unilateral or bilateral osteoarthritis were equally allocated to one of the two randomised groups – Group I (n=35) patients received PRP as per protocol whereas Group II (n=35) patients underwent arthroscopic debridement. There were three major considerations while planning the study – (1) whether intra-articular use of platelet-rich plasma is feasible without complications, (2) whether platelet-rich plasma provides a clinical/functional improvement in patients with osteoarthritis knee, (3) whether the treatment response obtained for PRP is better than that obtained for arthroscopic debridement.et al10 in their study reported 57.9% patients in KL grade I-III and remaining 42.1% in grade IV. Wang-Saegusa et al11 on the other hand had 36.9% grade IV cases. However, we excluded patients of grade IV as also done by some of the other authors14. Patel et al15 in their study did not use KL-grade as criteria but instead used Ahlback grade and included patients with grades 1-3 only while excluding the more severe grade 4-5 patients. In this study, we also limited our evaluation for Grade 2 and 3 patients only.In our study, majority of patients (52.9%) had KL grade 3. Compared to this Kon In our study, we focused on the outcome parameters in both KL Grade 2 and KL Grade 3 patients independently as well as a combined overall outcome of both the grades. A statistical matching for WOMAC scores and VAS scores was done between both the groups at the start of study, for both the grades independently as well as a common assessment for both the grades and did not show a significant difference between two groups, thus depicting that both the groups were matched statistically for various clinic-demographic parameters as well as the outcome parameters.At all the three follow-up intervals, for overall assessment and KL Grade mean WOMAC scores were significantly lower in PRP group as compared to arthroscopy group, however, there was no significant difference between two groups when assessed for KL Grade 3. During different follow-up intervals, mean values were minimum at three months and maximum at nine months. For VAS scores too, in both the groups mean values were minimum at three months and maximum at nine months. At all the follow-up intervals, mean VAS scores were lower in PRP group as compared to arthroscopy group for both the grades independently as well as on overall combined assessment. A statistically significant difference between two groups was observed for KL Grade 2 and overall assessment at 3 months, for both KL2 and KL3 grades independently as well as for overall assessment at 6 months and for overall combined assessment only at 9 months.On the basis of overall assessment as well as for KL Grade 2, for WOMAC score, PRP showed a definite edge over arthroscopy, however, for KL Grade 3, the results of PRP were comparable to arthroscopy. With the passage of time, both the treatments seemed to lose their effectiveness. By 9 months, the percent reduction in WOMAC scores was only 9.49±9.80% in PRP group and -0.13±5.06% in Arthroscopic debridement group. At the last follow-up, percent reduction in VAS scores was 8.29±14.19% in PRP group as compared to 3.20±7.39% in Arthroscopic debridement group. At this time interval, a significant difference between two groups was observed only for WOMAC scores.So far, no comparative studies between PRP and arthroscopic debridement for management of knee osteoarthritis have been carried out and the present study is the first study in that direction. However, both the methods have been used extensively for management of knee osteoarthritis, either as a prospective single arm case series or a randomised trial comparing it with other popular treatment modalities.16. In this study, we observed the percent reduction in WOMAC scores to be negative at 9 months interval whereas for VAS scores this reduction was at nominal 3.20±7.39% on overall evaluation and 4.76±9.65%, and 2.15±5.42%, respectively for KL Grade 2 and 3. In their study Gaonkar et al16 reported improvement in only 32.1% patients undergoing arthroscopic debridement at one year interval. We found a nominal reduction in pain at 9 months, thus showing an even worse response as compared to that reported by Gaonkar et al16 in their study. Although, arthroscopy has been shown to be superior as compared to conventional drug therapy17, this superiority is only short-term and in long-term it has been reported to be comparable to conservative treatment18. The findings of present study also suggested that the efficacy of this treatment did not go beyond 9 months.As far as arthroscopic debridement is concerned, its efficacy has been stated to be limited to low grade osteoarthritis and long-term improvements are out of its scopeet al13 in their study found PRP to be effective up to 12 months of follow-up. In present study, we found PRP to be more effective in KL Grade 2 as compared to that in Grade 3, which is similar to the observation made by Filardo et al14 who also observed improvement trends in PRP to be favourable for low grade articular degeneration (KL Grade 2). In their study too, PRP offered a significant clinical improvement up to one year of follow-up. In present study, we also observed an improvement in both WOMAC and VAS scores up to 9 months in PRP group. In another study, Say et al19 observed PRP to be better than hyaluronic acid (HA) injections at 3 and 6 months follow-up. In present study, at both these time intervals we found PRP to be better than arthroscopic debridement. In another study, Patel et al15 compared efficacy of single injection and two injections of PRP against normal saline and observed both the regimens to be effective up to six months. In present study, we found the PRP treatment to be effective up to nine months. A number of other studies have shown sustenance of improvement in functional outcomes and pain for six months or more20. A number of meta-analyses have also shown it to be better as compared to other alternative therapies  or placebo23.However, PRP has emerged as a potential new modality with fast relief from pain and functional outcome that is sustainable up to a substantial period of time. In present study, for both WOMAC as well as VAS scores, reduction was observed up to nine months of follow-up. Gobbi et al (2012)12, Filardo et al (2012)14 and Say et al (2013)19 who also found PRP to be safe and effective and reported of mild pain and effusion at the injection site as the only complications.In present study, no complication or side effect was noticed in either of two groups at any point of time. These observations are similar to the observations of Spakova The limitations of the present study was that the outcomes were measured only for two domains – WOMAC scores and Pain. Another limitation is use of radiograph as only means of radiographic analysis due to cost constraints and MRI cartilage analysis could be used along with radiograph. Several other studies have studied the outcomes using other criteria too. Inclusion of subjective outcome in terms of patient satisfaction could also be included as assessment criteria. Moreover, the duration of follow-up could not be extended. A longer duration of follow-up would have been able to illustrate the point of time beyond which PRP loses its efficiency as seen for Arthroscopic debridement at nine months itself. In present study, we found that improvements in WOMAC scores and Pain were sustainable in PRP group as compared up to nine months of time period. In present study, we also found that PRP had higher improvement as compared to arthroscopic debridement for both KL2 as well as KL3 grades, however, owing to limitations of sample size, this difference was not significant statistically at some follow-up intervals. Hence, further studies with a larger sample size and a longer follow-up period with inclusion of other comparative treatment modalities are recommended. Nevertheless, PRP was found to be safe and efficacious treatment and could be recommended as an alternative management modality for osteoarthritis knee.At follow-up at three months, six months, nine months: (1) WOMAC score of patients administered PRP injection were lower than those subjected to arthroscopy. Though WOMAC score of patients with moderate osteoarthritis (KL Grade 3) were comparable between the above two groups, (2) VAS score of patients administered PRP injection were lower than those subjected to arthroscopy. Though VAS score of patients with moderate osteoarthritis (KL Grade 3) were comparable between the above two groups at follow-up at 3 months. In later follow-up (nine month) patients of above two groups had comparable VAS score when evaluated separately for severity of osteoarthritis (KL Grade). At final follow-up (nine months) reduction in WOMAC score was observed among cases administered PRP while increment in WOMAC score was observed among cases subjected to arthroscopy.Of the two treatment modalities, PRP seemed to have an edge over arthroscopic debridement, however, this efficacy was more pronounced for KL Grade 2 as compared to Grade 3. PRP was found to be safe and efficacious treatment and could be recommended as an alternative management modality for osteoarthritis knee.


Despite the long history of burnout studies, the problem of burnout among psychiatric specialists in Russia is insufficiently studied. The risk of burnout is the highest among psychiatrists in the first 10 years of their career.To assess the prevalence and severity of burnout in early career psychiatrists (ECPs) in Russia.An anonymous online survey of ECPs in Russia was conducted in July-August 2019 with a screening for burnout using the Maslach Burnout Inventory (MBI). The final sample consisted of 165 people . 95.2% of respondents lived in urban areas.2(1)=5.74; p=0.017). Mean values of the MBI Emotional Exhaustion scale corresponded to 23.33±8.97 and 17.97±8.49 , the MBI Depersonalization scale – 10.46±4.81 and 9.16±4.22 , and the MBI Personal Accomplishment scale – 33.02±5.98 and 35.32±5.75  for women and men, respectively. The following risk factors for professional burnout were identified: female sex , overlapping of several working positions , difficulties in work due to changes in documentation requirements introduced since the start of career .A high level of burnout according to at least one of the MBI scales was revealed in 71.5% of ECPs: in 79 (78.2%) women and 39 (60.9%) men (χA high frequency of burnout among ECPs in Russia was revealed which suggests the urgent need for studies assessing the ways to prevent burnout in psychiatrists in Russia.No significant relationships.


Primary central nervous system lymphoma (PCNSL) is a rare and aggressive disease. The role of surgical resection in PCNSL has always been the center of debate. Here we investigated the clinical and follow-up data of single lesion PCNSL operated in our center, focusing on the comparison between surgical resection and biopsy.All consecutive cases of single lesion PCNSL between October 2004 and December 2019 were retrospectively collected from the database of the Second Affiliated Hospital of Zhejiang University, School of Medicine. Patients were divided into resection group and biopsy group. Clinical information including age, gender, Karnofsky performance status, imaging features and postoperative treatment was collected from the medical records. All the patients were followed for survival analysis.p = 0.01) and therapeutic treatment  were independent prognostic markers with OS. Multivariable Cox regression analyses also revealed that only age  was independent prognostic marker for PFS.A total of 105 patients with PCNSL were finally involved in our analysis. Neither PFS nor OS were significantly different between the resection group and biopsy group. The univariate analysis revealed that age < 60 and therapeutic treatment were significant predictors of longer PFS and OS. In the multivariate analysis, age (HR = 3.09, 95% CI 1.31–7.28, In single lesion PCNSL, there was no significant difference between the resection group and biopsy group for both PFS and OS. Younger age and postoperative treatment have been proved to be indicators of better prognosis. Primary central nervous system lymphoma (PCNSL) is a rare and aggressive disease, which accounts for 4% of primary central nervous system (CNS) neoplasms and 4%-6% of extranodal lymphomas. Despite advances of anti-cancer treatment modalities, the majority of the patients suffered from disease progression within the first 2 years after initial diagnosis, with a median relapse time of 10 to 18 months . Unlike Studies during the period of 1970s-2000s have demonstrated unfavorable complication rates and marginal benefits of surgical resection in PCNSL . Indeed,All consecutive cases of PCNSL between October 2004 and December 2019 were retrospectively collected from the database of the Second Affiliated Hospital of Zhejiang University, School of Medicine in China. Patients all underwent either surgical resection or biopsy. Pathology was determined by an expert pathologist in all cases and based on International Classification of Diseases (ICD) code 9590/3. Patients with multifocal lesions (≥ 2 lesions), those with systemic lymphoma, those pregnant or nursing, or those for whom survival information were not available were excluded from analysis. And only patients with single lesion was included in this analysis.Clinical information including age, gender , Karnofsky performance status (KPS), tumor location, size, surgical intervention and postoperative treatment was collected from the medical records. Postoperative management was defined as palliative support, and therapeutic treatment which including radiotherapy(RTx) only, chemotherapy(CTx) only and combined treatment. MRI or CT images were reviewed to record the following variables: tumor location, involvement of deep brain structures , maximum visible diameter of the lesion. Patients were divided into resection group and biopsy group according to the operation records. Resection was defined as surgery with intent for maximal cytoreduction that achieved subtotal or gross-total resection, whereas biopsy was defined as the obtaining of tumor tissue for diagnostic purposes only. The surgical procedure was determined by assessment of the operative report, the neurosurgeon’s and neurooncologist’s documentation and postoperative imaging, when available. Gross total resection (GTR) was defined as removal of 95% of the tumor, while the rest was considered as subtotal resection (STR) , 13. Posp values less than 0.10 in the univariate analysis or variables concerned in clinical trial were involved in the multivariate analyses, using Cox proportional hazards regression model. p < 0.05 was confirmed as statistically significant.Analysis was performed using SPSS version 25.0 for windows. Descriptive statistics were reported as a median with a range or frequency with percentage. Survival curves were generated using the Kaplan–Meier’s methods by GraphPad Prism 8.0.2. The OS and PFS were compared by the log-rank test in the univariate analysis. All variables with n = 25, 23.8%), followed by cerebellum , corpus callosum  and basal ganglia . Deep brain involvement were observed in 57 patients (54.3%). 71.6% lesions were larger than 3 cm. Information about postoperative treatment was available for 77(73%) patients. Among them, only 5(6.5%) patients received palliative treatment due to low KPS, old age, economic problems or other unknown causes. 10 patients (13.0%) received radiotherapy alone, 31 patients (40.3%) received chemotherapy alone, and 31 patients (40.3%) received both radiotherapy and chemotherapy . The male to female ratio was 1.2:1 (57:48). 60 patients (57%) underwent resection, and 45 patients (43%) underwent biopsy. In the surgical resection group, 34(57%) patients had GTR and 26(43%) patients had STR. Only one case underwent open biopsy, and the rest cases all used method of stereotactic biopsy. The most commonly involved site was the frontal lobe (Neither PFS nor OS was significantly different between the resection group and biopsy group. Median PFS of the resection group was 29.3 months 95%CI 10.9–47.6) versus 44.0 months (95%CI 35.9–52.1) of the biopsy group. Patients who underwent resection had a median OS of 64.2 months (95%CI 29.0–99.4) compared to 59.9 months (95%CI 32.6–87.2) of the biopsy group. The extent of resection also showed no significant difference for either PFS or OS. The median PFS and OS of patient who underwent STR were 34.6 months (95%CI 5.4–63.9) and 41.7 months (95%CI 27.0–56.4) respectively, while the median PFS and OS of patients with GTR were 25.2 months (95%CI 12.2–38.2) and 64.2 months (95%CI 15.3–113.0) respectively  in the resection group and 8 patients (17.8%) in the biopsy group experienced at least one complication. Regional complication occurred in 1 patient (1.7%) after resection and 8 patients (17.8%) after biopsy. Neurologic complication occurred in 7 patients (11.7%) after resection and 5 patients (11.1%) after biopsy. Operational related mortality happened in 1 patient, due to intracranial infection after craniotomy.With a median follow-up of 36.2 months (range 0.6–188.3), 60 patients had experienced disease progression and 52 patients died of the disease, resulting in a median PFS of 38.4 months (95%CI 23.3–53.5) and median OS of 64.2 months (95%CI 31.5–96.8). A univariate analysis was performed for 4 potential prognostic factors including age, deep brain involvement, tumor size and postoperative treatment, which revealed that age < 60 had significantly better OS and therapeutic treatment had significantly longer PFS and better OS  and therapeutic treatment  were independent prognostic OS markers (Table p = 0.04) was the independent prognostic marker of PFS.In the multivariate Cox regression analysis, age (HR = 2.98, 95% CI,1.10–8.07, PCNSL is a rare and aggressive brain malignancy with an unsatisfactory outcome associated with its complex pathogenesis and uncertain therapeutic approach. The most important risk factor for PCNSL is immunodeficiency including drug induced, infection relevant or congenital. The immunodeficiency status of patients might cause more intense side effect of treatment . And theSurgery is discouraged for PCNSL according to the current treatment paradigm which is based on older studies. The impactful study of DeAngelis reported a 40% complication rate associated with resection of PCNSL . Both BeOur results were in accordance with previous studies on PCNSL  and showIn this study, there was no significant differences of OS or PFS among patients receiving chemotherapy, radiotherapy or both. But the median OS of patients receiving only radiotherapy was slightly longer than those receiving combine therapy. Some researches showed that the combination of HD MTX and WBRT was associated with disabling neurotoxicity with an incidence rate of 25% to 35% and related mortality rate of 30% , 28. ThiThis study has several limitations including similar biases present in other retrospective studies. The majority of patients who underwent resection and were diagnosed with PCNSL were chosen for resection instead of a biopsy due to radiographic diagnostic ambiguity, which is not uncommon in PCNSL, combined with the surgeon’s experience and preference. And different from those typical PCNSL, these patients might show uncommon features. Thus in our analyses, the resection group had lower age, more superficial lesions. And once a patient imaging diagnosed prefer to PCNSL, our institution would more like to biopsy first followed with chemotherapy except whom was under significant mass effect and high intracranial pressure. And since patients’ condition in biopsy group would be milder, they would be more accepted to chemotherapy. Even though the size of our series was remarkable for a single-center study, the number of patients might still be inadequate to detect the real impact of surgery in this rare disease. We did not collect sufficient data of post-operational therapy. Additionally, we did not subclass the chemotherapy regimens for further survival analysis, although it was known that patients with different chemotherapy regimens tend to have different prognosis. Further multicenter prospective studies are necessary to confirm our results.In this study, we found no significant difference between the resection group and biopsy group for both PFS and OS in single lesions PCNSLs and therefore we do not advocate resection as first-line treatment. The hypothesis of considering PCNSLs as a whole-brain pathology might explain the limited effect of surgical resection. However, in single lesion PCNSL, craniotomy might play a role in cases with significant mass effect and high intracranial pressure. Further study is needed.


Faecalibacterium, Escherichia-Shigella, and Bacteroides can significantly enrich the sediment. Our study revealed the characteristics and preliminary interaction of fish and environmental microbiota in the IPRS. It provided a reference for evaluating microbial health status in the application of IPRS in large water bodies’ aquaculture.Due to its ability to collect and remove aquaculture waste, an in-pond raceway system (IPRS) has been used to decrease the uncontrolled waste discharge in the traditional cage aquaculture method in large water bodies. However, when applied to large water bodies, its environmental performance is still lacking. This study focused on analyzing the microbial characteristics and the interaction between largemouth bass (gill and gut) microbiota and the environment (water and sediment) microbiota of an IPRS. Further, it revealed the primary relationship from the perspective of microbiota in the IPRS. The results show that (1) the alpha diversity of microbiota in the water is significantly lower than that of fish and sediment. The relationship between water microbiota and fish microbiota is limited. (2) The water microbiota inside and outside the tank showed high similarity and were not significantly affected by environmental factors. (3) The SourceTrack analysis showed that fish microbiota is one of the primary sources of sediment microbiota, and more than 15% of the sediment microbiota come from fish. Microbes such as  It began to emerge in the late 1970s and then developed rapidly . In 2019products . The larproducts ,6. In adproducts . ExploriAn in-pond raceway system (IPRS) is an efficient recirculating aquaculture system (RAS) that separates the intensive aquaculture and water purification areas. IPRS has a complete set of mechanical facilities to promote water flow, collect waste, and pump sewage ,10,11. IMicropterus salmoides) is a farmed species with important economic value; the aquaculture production of largemouth bass in China has rapidly increased from 347.3 thousand tons in 2016 to 619.5 thousand tons in 2022, with an output value of US$1.76 billion [Largemouth bass . Standard bacterial V3-V4 region universal primers 338F (ACTCCTACGGGAGGCAGCA) and 806R (GGACTACHVGGGTWTCTAAT) were used for PCR amplification. Sequencing libraries were prepared using the TruSeq Nano DNA LT Library Prep Kit from Illumina. Before sequencing, the library was first checked on the Agilent Bioanalyzer using the Agilent High Sensitivity DNA Kit. Afterward, the library was quantified on the Promega QuantiFluor fluorescence quantitative system using the Quant-iT PicoGreen dsDNA Assay Kit. Paired-end sequencing was performed by a MiSeq 2 × 300 bp sequencer.https://www.r-project.org).First, the primers and barcodes were removed from the raw data of high-throughput sequencing, and the corresponding samples were identified and assigned. The microbiome bioinformatics analysis was performed using QIIME 2 2022.2 . Raw seqp > 0.05, p > 0.05, p < 0.05, p < 0.01, The alpha diversity of fish and environment microbiota was compared. Observed features represent the number of observed ASVs, Shannon accounts for both the abundance and evenness of the taxa present. Faith pd represents the measures of biodiversity, which incorporate the phylogenetic difference between species. There are no significant differences between the gut and gill of largemouth bass  of the phylum Fusobacteriota, the genus Plesiomonas (13 ± 7.4%) of the phylum Proteobacteria, and the genus Mycoplasma (9.4 ± 6%) of the phylum Firmicutes constituted the main microbiotas in the fish gut (Aeromonas (8 ± 7.3%) of phylum Proteobacteria, the inaccurately classified genus of the Lachnospiraceae family of phylum Firmicutes (5.8 ± 1.2%), and the family Rhodobacteraceae of phylum Proteobacteria  and CL500-29 marine group (11 ± 0.61%) of the phylum Actinobacteriota and the genus Clade III (17 ± 0.47%) of the phylum Proteobacteria constituted the main genera (The main microbes in the water were composed of Proteobacteria (44 ± 0.75%), Bacteroidota (10 ± 0.68%), and Actinobacteriota (42 ± 1.1%) at the phylum-level . At the n genera .p > 0.05, p < 0.05, p > 0.05). Comparing the water quality factors inside and outside the tank, no significant difference was found  and aerobic chemoheterotrophy (8.1 ± 0.7%) were the main functions of microbiota in water. Aromatic compound degradation (1.8 ± 0.52%), methylotrophy (1.4 ± 0.075%), and methanol oxidation  of phylum Bacteroidota constituted the main genera of the sediment (The main phylum-level composition of sediment microbiota was Bacteroidota (20 ± 1.4%), Proteobacteria (15 ± 1.6%), and Firmicutes ; the other two ASVs were also more than 1%; Escherichia-Shigella was 1.1 ± 0.65%, and Bacteroides plebeius was 1.3 ± 0.49% , fermentation (23 ± 4.7%), and aerobic chemoheterotrophy (4.5 ± 0.79%) were the main functions of sediment microbiota d. XylanoCetobacterium, Plesiomonas, and Mycoplasma were the major bacteria constituting the gut microbiota of largemouth bass. Our result is highly consistent with previous studies on the gut microbiota of largemouth bass [Maintaining microbial homeostasis in fish has important implications for host health ,40,41. Tuth bass ,43, indiAeromonas of the phylum Proteobacteria and an inaccurately classified genus of the Lachnospiraceae family of the phylum Firmicutes. Aeromonas is a pathogen that causes red sore in largemouth bass [Aeromonas in this study was mainly caused by a single sample  and the environment (water and sediment) in the IPRS. The water microbiota in the IPRS had the lowest alpha diversity and minimal impact on fish microbiota. Comparisons at both the microbiota community- and genus-levels showed similar water microbiota inside and outside the tank. One of the important sources of sediment microbiota is fish microbiota in the IPRS.


Background and Aim: Polyhydramnios is associated with an increased risk of various adverse pregnancy outcomes, yet complications during labor have not been sufficiently studied. We assessed the labor and perinatal outcomes of idiopathic polyhydramnios during term labor. Methods: Retrospective cohort study at a tertiary medical center between 2010 and 2014. Women with idiopathic polyhydramnios defined as an amniotic fluid index (AFI) greater than 24 cm or a deep vertical pocket (DVP) > 8 cm (cases) were compared with women with a normal AFI (5–24 cm) (controls). Statistics: Descriptive, means ± SDs, medians + IQR. Comparisons: chi-square, Fisher’s exact test, Mann–Whitney Test, multivariate logistic models. Results: During the study period 11,065 women had ultrasound evaluation completed by a sonographer within two weeks of delivery. After excluding pregnancies complicated by diabetes , fetal anomalies, IUFD, multifetal pregnancies, elective cesarean deliveries (CD) or missing data, we included 750 cases and 7000 controls. The degree of polyhydramnios was mild in 559 (75.0%) cases (AFI 24–30 cm or DVP 8–12 cm), moderate in 137 (18.0%) cases (30–35 cm or DVP 12–15 cm) and severe in 54 (7.0%) cases (AFI >35 cm or DVP > 15 cm). Idiopathic polyhydramnios was associated with a higher rate of CD 9.3% vs. 6.2%, p = 0.004; a higher rate of macrosomia 22.8% vs. 7.0%, p < 0.0001; and a higher rate of neonatal respiratory complications 2.0% vs. 0.8%, p = 0.0001. A multivariate regression analysis demonstrated an independent relation between polyhydramnios and higher rates of CD, aOR 1.62 (CI 1.20–2.19 p = 0.002) and composite adverse neonatal outcome aOR 1.28 (CI 1.01–1.63 p = 0.043). Severity of polyhydramnios was significantly associated with higher rates of macrosomia and CD (p for trend <0.01 in both). Conclusions: The term idiopathic polyhydramnios is independently associated with macrosomia, CD and neonatal complications. The severity of polyhydramnios is also associated with macrosomia and CD. Amniotic fluid volume assessment at term using prenatal ultrasound is common for various indications. Examples include fetal biophysical profile studies, assessment of post term pregnancies or decreased fetal movements and when assessing fetal weight. Variations in amniotic fluid volume have been considered an indicator of adverse perinatal outcome ,3,4,5,6.Polyhydramnios prevalence ranges from 0.2% to 2.0% . It is dMaternal, fetal and placental conditions associated with polyhydramnios include maternal diabetes mellitus, rhesus iso-immunization, congenital and chromosomal abnormalities and multiple gestation. However, in as many as 70.0% of cases, no cause is found antenatally and the polyhydramnios is referred to as idiopathic .Previous reports have shown polyhydramnios to be associated with intrauterine fetal death (IUFD), preterm delivery, an unstable lie, malpresentation, cord prolapse and placental abruption ,10,11.However, studies examining the association between idiopathic polyhydramnios, its severity and the fetal and maternal outcome during labor are scarce. We therefore undertook this study to assess the perinatal outcome of term idiopathic polyhydramnios.We performed a retrospective cohort study of all women with a singleton pregnancy who delivered at term (37.0–42.0 weeks of gestation). All women included in the study had an ultrasound completed in our hospital either as they were having antenatal care within our system, or had a labor and delivery triage visit due to various reasons such as false labor, preterm labor and so on. Hence, the diagnosis of polyhydramnios or the normal amount of amniotic fluid was based on an ultrasound performed at our hospital within 14 days of term delivery. We aimed to assess the perinatal outcome of term idiopathic polyhydramnios. Our clinical practice regarding management of term polyhydramnios has changed over time, specifically since the publication of the landmark study by Pilliod et al.  from 201Data were extracted de-identified from our computerized database, which includes participants’ demographics, procedures, diagnoses and other pertinent coding, all of which was extracted from the electronic medical record and are updated during hospital stay.Women with idiopathic polyhydramnios were defined as those with amniotic fluid index (AFI) greater than 24 cm or a deep vertical pocket (DVP) > 8 cm (cases) and were compared with women with a normal AFI (5–24 cm) (controls). Ultrasound examinations were performed by either a registered and trained sonographer or a maternal fetal medicine-trained physician, using GE-Voluson E8, Expert, 6–12 MgH or voluson 730.Shaare Zedek Medical Center is a university-affiliated tertiary medical center with a large obstetric service. Roughly fifteen thousand deliveries are attended to annually. National Health and Drug Insurance plans cover all women for antenatal and peripartum care. At our medical center the real-time computerized medical records are continuously updated in real-time during labor and delivery by attending healthcare professionals. The data are audited intermittently by trained technical personnel to guarantee validity of the data. Demographic and obstetric characteristics, as well as outcome data as defined and detailed below, were extracted from the electronic database management software. Hence, for this study we did not use diagnosis codes, but rather the diagnosis as registered in the database, based on course of labor, postpartum course and the discharge letters of the mother and the newborn.The primary outcome was the mode of delivery: vaginal delivery (spontaneous or assisted) vs. cesarean delivery (CD). Secondary outcomes were maternal and neonatal adverse events. Maternal adverse events included postpartum hemorrhage , chorioamnionitis, placental abruption, shoulder dystocia, perineal tear grade 3 and 4 (OASIS) and readmission to the hospital within 6 weeks. Definitions: Obstetrical anal sphincter injury (OASIS) classified as perineal tear grade 3 which involve the external and/or internal sphincter or perineal tear grade 4 which involve the rectal mucosa. OASIS is diagnosed by an obstetrician and corrected in the operating room. Postpartum hemorrhage (PPH) blood loss of over 500 mL after vaginal delivery and over 1000 mL after CD.Neonatal adverse events included the following: 5-min Apgar score < 7, neonatal intensive care unit (NICU) admission for >72 h, macrosomia (birthweight > 4000 g), jaundice (defined as a need for phototherapy), Hypoglycemia (<40 mg/dL), respiratory complications , metabolic complications, sepsis, asphyxia, convulsions, necrotizing enterocolitis (NEC), clavicle fracture, intraventricular hemorrhage (IVH) and neonatal death. Neonatal adverse events were derived from newborn discharge records as documented by the neonatologist. Composite adverse neonatal outcome were defined as the presence of one or more of the neonatal adverse events.Descriptive continuous variables were reported as median and interquartile ranges or mean ± SD. Categorical variables were reported as counts and proportion. Univariate analyses included Chi-square test or Fisher exact test to compare between categorical variables. The effect of polyhydramnios on continuous variables was tested by unpaired student T-test or Mann–Whitney test. The choice of a parametric or nonparametric test depended on the distribution of a continuous variable. p-for-trend. Subgroup analysis was performed in order to assess the impact of polyhydramnios on CD in nulliparous deliveries. The “dose–response” relationship between the severity of polyhydramnios and outcomes was tested and reported with Two multivariable logistic regression analyses were developed in order to check for an independent association between polyhydramnios and (1) CD and (2) any neonatal complication. Covariates in the models included maternal age, ethnicity, hypertensive disorder of pregnancy, nulliparity, prior miscarriages, prior CD, induction of labor, use of epidural analgesia, oxytocin augmentation during labor and extreme neonatal weights defined as small for gestational age (>10th percentile) and large for gestational age (<90th percentile) based on Israeli neonatal birthweight charts by Dollberg S. et al. .The discriminatory power of the models were examined using c statistics (AUC). Odds ratios (OR) with 95% confidence intervals (CIs) were reported.p < 0.05 was considered statistically significant. Analyses were carried out using IBM SPSS version 22 statistical package. All comparisons were two tailed, and The study protocol was approved by the institutional Helsinki Committee (IRB number P24.15).During the study period, a total of 11,065 women had ultrasound evaluation completed within two weeks of delivery. There were 9919 women (89.6%) who had normal or low amniotic fluid and 1146 women (10.4%) who had polyhydramnios. After applying exclusion criteria, there were 7000 women (90.3%) with normal AFI (controls) and 750 women (9.7%) with polyhydramnios (study group). The degree of polyhydramnios was mild in 559 (75.0%) cases, moderate in 137 (18.0%) cases and severe in 54 (7.0%) cases.p = 0.191. There were no significant differences in the polyhydramnios rate over the study period (range of 8.5–11.2%), p < 0.0001). The percent of women at advanced maternal age (age >35 years) was also higher in the study group as compared to the control group 17.3% vs. 12.9%, (p = 0.001). Women in the study group were less likely to be nulliparous, with 23.0% compared to 35.0% in the control group (p < 0.0001). The median [IQR] time between the ultrasound and the delivery was similar in both groups.Clinical and demographic characteristics of women are presented in p = 0.004. Furthermore, primiparous women with polyhydramnios compared to multiparous women had a higher incidence of CD 19.1% vs. 10.1% (p < 0.0001). The CD rate was also higher in woman with moderate/severe polyhydramnios vs. those with a normal amount of amniotic fluid or mild polyhydramnios (12.6% vs. 6.4% p = 0.001). Indications for CD differed between the groups and are presented in p = 0.005). There were two cases of umbilical cord prolapse in women with polyhydramnios (0.3%) and five cases in the control group (0.07%). Severity of polyhydramnios was significantly associated with higher rates of macrosomia and CD (p for trend <0.01 in both) as presented in p = 0.002) AUC 0.83 (95%CI 0.81–0.85).Primary outcome: Women with polyhydramnios had a higher incidence of CD: 9.3% vs. 6.2% p = 0.546). The median duration of the first stage of labor was similar between the groups (239 min vs. 219 min p = 0.101), whereas median duration of the second stage of labor was shorter in the study group (110 vs. 99 min p = 0.005). The rate of meconium-stained amniotic fluid was higher in study group 21.1% vs. control group 17.7% p = 0.023. There were no differences between the groups regarding the rates of induction or augmentation of labor, use of epidural analgesia or rate of chorioamnionitis, placental abruption, shoulder dystocia, perineal tear grades 3 and 4 or post-partum hemorrhage. A composite adverse maternal outcome  was higher in study group vs. control group (164 (21.9%) vs. 1266 (18.1%) p = 0.011).Labor characteristics are presented in p < 0.0001)), and there was a higher rate of macrosomia in the study group ). The macrosomia rate was also significantly more common in women with moderate/severe polyhydramnios vs. those with a normal amount of amniotic fluid or with mild polyhydramnios (31.4% vs. 8% p < 0.0001). There was a higher rate of neonatal respiratory complications in the study group 2.0% vs. 0.8%, (p < 0.0001). There were no differences between the groups in the rate of NICU admission > 72 h 1.1% vs. 0.7% (p = 0.25) and low Apgar scores (defined as Apgar score <7 at 5 min) 0.9% vs. 0.6% (p = 0.202).Neonatal characteristics and outcomes are presented in p = 0.043) AUC 0.58 (95%CI 0.56–0.6).A composite adverse neonatal outcome occurred in 12.5% of mild polyhydramnios, 13.9% of moderate polyhydramnios and 7.4% of severe polyhydramnios compared to 9.3% for controls. There were no neonatal deaths in either group. Multivariate regression models accounting for various characteristics as detailed in the method section revealed that polyhydramnios was independently associated with composite adverse neonatal outcome, aOR of 1.28  has been related to polyhydramnios, in our study, PROM was less common in the study group of idiopathic polyhydramnios than the control group. A possible mechanism underlying this finding may be the high incidence of PROM of around 10% at term with the general population of pregnant woman .Indeed, the rate of polyhydramnios in our study is much higher than what has been previously reported, yet it should be noted that the true prevalence is unknown.Our study has strengths and limitations. The limitations include the following: this was a retrospective study and has the inherited limitations of retrospectively collected information. During the study period, there were roughly 50,000 term singleton deliveries; however, only 20% of those had an ultrasound exam in our institution within 2 weeks of delivery. It is, therefore, possible that our study suffers from selection bias. As noted, there are several differences between study groups; for instance, 23% of women with polyhydramnios were nullipara, vs. 35% of the women in the control group. We do not have data regarding the BMI of parturients as this information was not routinely collected during these years. We do not have information regarding infection screening as a cause for polyhydramnios, but the significance of investigating infectious causes has not been shown to be beneficial in the workup of polyhydramnios ,29. FurtThe strengths of our study include the large sample size and the fact that this is a historical cohort before our departmental protocol was changed to offer induction of labor for women with idiopathic polyhydramnios at term. Even though women had an ultrasound exam within 2 weeks of delivery, the median time from ultrasound to delivery was not different between the groups. Furthermore, we included in this study only women without diabetes and without fetal/neonatal anomalies.We found that term idiopathic polyhydramnios is independently associated with macrosomia CD and neonatal complications. Additionally, the severity of polyhydramnios was found to be associated with macrosomia and CD. The information from this study will assist health care providers in counseling their patients with term idiopathic polyhydramnios regarding the expected mode of delivery according to the severity of polyhydramnios, and will allow the NICU team to be prepared for possible respiratory difficulties in the neonates of this group.


Escherichia coli Nissle 1917 (EcN) during production and storage. Labneh was manufactured with PFPP (0.5% and 1%) and analyzed at 0, 7, and 15 days of cold storage for postacidification and sensory properties and viability of EcN, survival of EcN to simulated gastrointestinal tract stress, and adhesion potential of EcN to Caco-2 cells. Acidification kinetics during fermentation showed that supplementation with PFPP reduced the time needed to decrease pH and reach the maximum acidification rate. PFPP addition contributed to postacidification of labneh during storage. PFPP had a beneficial effect (p < 0.05) on counts of EcN in labneh during different storage periods. Consumer preference expectations for labneh enriched with PFPP (0.5% and 1%) were higher than those for the control. PFPP provided a significant protective action for EcN during simulated gastrointestinal transit and had a positive effect on EcN adhesion to Caco-2 cells in vitro, although this decreased during storage with labneh. Labneh supplementation with PFPP can be recommended because of the positive effect on EcN viability and the high nutritional value, which may increase the appeal of the product to consumers.Passion fruit peel powder (PFPP) was used to supplement the probiotic labneh to increase the activity of  Consumers have become increasingly aware of the positive influences of food on health promotion, and this has led to a development in the global market of functional foods. These are foods that can be considered dietary items, which, besides providing energy and nutrients, beneficially modify one or more targeted functions in the body by decreasing the risk of disease and/or by improving a specific physiological response . Foods tProbiotic bacteria are live microorganisms that provide positive impacts to the host when ingested in appropriate numbers. Studies show that probiotic bacteria exert beneficial influences on the gut and the immune system, reduce symptoms associated with irritable bowel syndrome, decrease adverse effects of antibiotics, help alleviate abdominal pain from lactose intolerance, and have antitumor and antimicrobial characteristics .Escherichia coli Nissle 1917 (EcN) is a Gram-negative bacteria with probiotic characteristics that was isolated by Alfred Nissle from the feces of soldiers who had not been infected during a Shigellosis outbreak [E. coli [outbreak . EcN lac[E. coli . Additio[E. coli ,6. EcN h[E. coli . Several[E. coli .Dairy products such as cheese, fermented milk, labneh, and yogurt are the most important carriers of probiotic bacteria in the probiotic food industry . StraineFermented milk products can be supplemented with many ingredients to improve their nutritional benefits and stimulate the growth and activity of probiotic bacteria during refrigerated storage periods . These bPassiflora edulis Sims f. flavicarpa Deg.) is a tropical fruit that is highly appreciated worldwide [Tropical fruits are a plentiful source of minerals, antioxidants, and vitamins. The passion fruit , nonessential amino acid solution, streptomycin, penicillin, Triton X-100, and fetal bovine serum were purchased from Sigma Aldrich . MacConkey agar, tryptone soya broth (TSB), tryptone soya agar (TSA) and tissue culture media were purchased from Thermo Fisher scientific .Escherichia coli strain Nissle 1917 (EcN) was taken from stock strains collection of dairy microbiology laboratory . EcN were cultured in TSB at 37 °C for 20 h. Individual colonies were then transferred to MacConkey agar and then incubated at 37 °C for 20 h. After microscopic control, EcN was three times re-inoculated and finally grown on TSA. Working culture of EcN was propagated 3 times using a 2% (vol/vol) inoculum in TSB at 37 °C for 20 h before use. Caco-2 cell line (ATCC HTB-39) was obtained from American Type Tissue Culture Collection (ATCC).Passion fruit peels were dried in an air drier at 55 °C until a constant weight was reached. The dried peels were then ground into a fine powder using a domestic grinder (BRAUN MQ 60), followed by sieving through a mesh sieve to obtain a particle size of <42 µm to ensure that PFPP could be easily reconstituted in milk.E. coli Nissle 1917 (2% v/v). The inoculated mixture was incubated at 37 °C until complete coagulation. The resulting curd was refrigerated and filtered through cloth bags at 5 °C for 12 h to concentrate the fermented curd by removing the whey from the curd; NaCl was then added to 1%. The obtained labneh was transferred into small plastic jars (200 mL) and stored at 5 °C for 15 days. Sample analysis was conducted in triplicates at 0, 7, and 15 days during the refrigerated storage.Probiotic labneh was produced according to Balabanova et al.  with sliVmax), expressed in 10−3 pH min−1; (2) the time at which Vmax was reached (h); (3) the time (h) required to reach pH 5.0 (TpH 5.0); (4) the time (h) required to reach the end of fermentation (pH 4.5) (TpH 4.6); and (5) pH at Vmax (pH Vmax).The fermentation kinetics were determined according to Casarotti, Carneiro and Penna . The ratThe postacidification of labneh was determined at 1, 7, and 15 days of refrigerated storage by measuring the sample pH in triplicate. Additionally, the acidity in tested samples was assessed using titration with 0.1 N NaOH; the total acidity was expressed as lactic acid percent/100 g .E. coli Nissle 1917 for each treatment were determined in triplicate at 1, 7, and 15 days of cold storage by using the pour plate technique. Briefly, 1 g of labneh sample was diluted in 9 mL sterile saline (0.85% NaCl). Bacterial counts were enumerated using MacConkey agar after incubation for 24 h at 37 °C. This result was expressed as colony-forming units/g of labneh (Log CFU g−1).Cell counts of Sensory analysis of probiotic labneh samples was evaluated at 23 °C under white light and in individual booths. The evaluation of sensory properties of tested samples was conducted in terms of appearance, texture, color, flavor, sourness, and general acceptability according to a 9-point hedonic scale, where 9 = like extremely, 8 = like very much, 7 = like, 6 = like slightly, 5 = neither like nor dislike, 4 = dislike slightly, 3 = dislike, 2 = dislike very much, and 1 = dislike. Consumer acceptance of tested samples was scored by 25 faculty members and students from the Faculty of Agriculture, Mansoura University, Mansoura, Egypt .4H2Na.2H2O and 150 mL of 1 M NaOH dissolved in distilled water and diluted to 1 L). Pancreatin (from the porcine pancreas) and bovine bile were added to 1 and 10 g/L, respectively. Samples were incubated for 2 h at 37 °C (enteric phase 1). Finally, the sample pH was readjusted to between 7.0 and 7.3 using the same alkaline solution. The pancreatin and bile concentrations were adjusted to 1 and 10 g/L, respectively, and samples were reincubated for 2 h at 37 °C (enteric phase 2). Aliquots of 1 mL were collected from triplicate samples at the beginning of the assay and after the end of each stress stage and then precipitated by centrifugation (6000× g for 15 min) and washed three times by resuspension in 3 mL of phosphate-buffered saline (PBS) (pH 7.5), followed by reprecipitation as described above. EcN cells were then resuspended in PBS (3 mL), and bacterial survival was determined as described in the microbiological analysis section.The effect of PFPP on EcN survival in labneh in GI tract-simulated conditions was assessed as reported by Buriti et al. , with mo5 cells/well) were seeded into 24-well tissue culture plates and incubated in 5% CO2 at 37 °C until a confluent monolayer had formed; media was changed with antibiotic-free medium (DMEM) 24 h before adhesion was assessed. All traces of the medium were then removed from the monolayer by washing once with PBS (pH 7.4). An aliquot of 1 mL of each labneh sample was added to confluent Caco-2 cell monolayers, followed by incubation in 5% CO2 at 37 °C for 2 h. Cells were then washed at least three times with PBS to eliminate nonadherent bacterial cells. Triton X-100 (1 mL) was added to each well to detach bacterial cells. To evaluate adhesion potential, the suspension (1 mL) from each well was then transferred to a sterilized tube containing 9 mL of sterile saline (0.85% NaCl), serially diluted, and plated on the MacConkey agar in triplicate. The percentage of adhered bacteria was calculated by dividing the viable bacterial counts adhered to the cell layers by the viable bacterial counts from the labneh before the adhesion assay. The experiment was conducted in triplicate.The Caco-2 cell line (ATCC HTB-39) was cultured in DMEM enriched with a 1% solution of nonessential amino acids, a mixture of streptomycin (100 μg/mL) and penicillin (100 IU/mL), and 20% fetal bovine serum. An assessment of cell adhesion was conducted as reported by Ranadheera et al. (2012), with slight modifications. Briefly, Caco-2 cells , hierarchical cluster analysis (HCA) and contour plot of preference and preference map were performed using the XLSTAT program.All tests were carried out in triplicate. ANOVA test with the significance level at The chemical composition of PFPP is presented in p ˂ 0.05) the initial pH of milk with 0.5% or 1% PFPP from 6.61 ± 0.03 to 6.4 ± 0.02 and 6.33 ± 0.02, respectively. Generally, the labneh without or with PFPP showed similar trends in pH changes. The pH of labneh enriched with 0.5% PFPP or control underwent a minor decrease in the first 60 min, but then decreased rapidly until the end of fermentation. However, the pH of labneh enriched with 1% PFPP decreased within the first 30 min, which was followed by a sharp decrease until the end of fermentation. The effect of PFPP addition on the tendency of changes in the labneh pH during the fermentation processes was consistent with the labneh fermentation kinetic trends  differences were present between the pH of labneh enriched with 0.5% of PFPP (4.42 PFPP labneh and 4.48 control) and labneh enriched with 1% of PFPP (4.37 PFPP labneh and 4.48 control) (p < 0.05). Titratable acidity varied from 0.86 to 1.05 mg lactic acid/g. There was also a significant increase in acidity induced by PFPP addition to labneh (p < 0.05).p < 0.05), which ranged from 4.32 to 4.39 among the treatments, which continued for the full 15 days of treatment (p < 0.05) (p < 0.05). At both 7 and 15 days, the labneh enriched with 1% of PFPP had the highest values of average titratable acidity (p < 0.05).After 7 days of storage, all the labneh samples showed a significant reduction in pH ( < 0.05) . The dec < 0.05) . After 710 cfu/mL in labneh without PFPP  on the EcN population in labneh during different times of the storage period, where the counts of EcN increased significantly (p ˂ 0.05) from 7.66 to 8.33 log10 cfu/mL in PFPP incorporation at day 0  at different times of storage period  explained 95.76% of the variability in two PCs A. PC1 7A. The trTo verify whether the participants enrolled in the study formed preference clusters, hierarchical cluster analysis was used. This has the potential to imagine the existence of two parts, in both regions, as shown in the obtained dendrogram B. One grConsumer division according to acceptance data provided three evaluation clusters: cluster 1 (40% of consumers), cluster 2 (30% of consumers), and cluster 3 (30% of consumers). p ≤ 0.05) in the population of EcN during transit of the food matrix through simulated GI-tract stress (10 CFU/mL among the populations of EcN in supplemented labneh and control at the completion of the in vitro experiment. The reduction in the EcN population after the in vitro assay was affected by continued storage (We then assessed the tolerance of EcN in probiotic labneh that had been exposed to simulated GI conditions . This prt stress . The pro storage .p ˂ 0.05) in EcN adhesion between the labneh treatments at different storage times (p ˂ 0.05) increased with increasing PFPP content  that is used for the production of probiotic labneh enriched with PFPP for tolerance to GI-tract stress and the ability to interact with human intestinal cells.Different types of fermented dairy products can act as carriers for delivering probiotic strains through the food matrix. products ,23. In tThe results obtained from chemical composition of PFPP in this study were similar with dos Reis et al. , who repp < 0.05). This behavior may be due to the high content of organic acids and polyphenols in passion fruit [Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus.The maximum acidification rate during fermentation was positively correlated with the concentration addition of PFPP  in titratable acidity increase and pH reduction during the shelf-life for all tested labneh samples. The fermentation of residual lactose and lactic acid production occur during the cooled storage period of labneh as a result of the metabolic activity of the starter culture [In this study, we detected significant differences , as reported in other studies using the different species [p ≤ 0.05) the capacity of EcN to adhere to Caco-2 cells, and this may be attributed to the low pH in labneh samples at the end of the storage period. The adherence ability of Enterococcus faecium strains to IPEC-J2 cells significantly decreased because of their pretreatment at pH 3.0 [To our knowledge, this is the first study to address the cellular adhesion of EcN suspended in labneh enriched with PFPP to assess the effect of supplementation of PFPP on ingestion of EcN in fermented milk. Using 7–8.8 log species ,42. Cert species . Low adh species . Extendet pH 3.0 . Deepikat pH 3.0  also indt pH 3.0 ,52. Howet pH 3.0 ,53.The increase of TPC after exposure to GIT stress has been attributed to some polyphenols with high molecular weight hydrolyzed into other compounds . AdditioThis study demonstrated that PFPP significantly affected the fermentation kinetics of the probiotic labneh. PFPP addition was conducive to a reduction in pH in the early stage of the fermentation process, which effectively activated the growth of EcN. During the fermentation, PFPP increased the fermentation rate and reduced the fermentation time. The pectin and polyphenols in PFPP exerted a positive effect on the survivability of EcN during in vitro transit through a simulated GI-tract environment. Furthermore, the addition of PFPP improved the survival of EcN during refrigerated storage of labneh. PFPP was also beneficial in increasing the adhesion rate of EcN to intestinal cells and improving the flavor, aroma, and general acceptability of labneh. Hence, it is feasible to produce functional labneh of superior quality by incorporating 0.5% to 1% PFPP. However, more studies are needed to explain the underlying mechanisms whereby PFPP influences EcN survival during transit of the GI tract and the adhesion potential of EcN to Caco-2 cells.


However, physiological reference values have not yet been sufficiently determined. The aim of the present study was to establish physiological reference values for shoulder offset parameters (SOPs). Methods: MRI images of the shoulder joints of 800 patients (mean age: 50.13 years [±16.01]) were analysed retrospectively. HO, GO, lateral glenoidal humeral offset (LGHO), humeral shaft axis offset (HAO) and cortical offset (CO) were measured. SOPs were examined for associations with age, gender, side and osteoarthritis. Results: The mean HO was 26.19 (±2.70), the mean GO was 61.79 (±5.67), the mean LGHO was 54.49 (±4.69), the mean HAO was 28.17 (±2.82) and the mean CO was 16.70 (±3.08). For all SOPs, significantly higher values were measured in male shoulders. There was a significantly (p < 0.001) higher mean value for HO, GO and LGHO in right shoulders. There was a significant correlation between age and LGHO, and HAO and CO, but not between age and HO or GO. Shoulders with osteoarthritis and non-osteoarthritis did not differ in the mean value of HO, GO, LGHO and HAO, except for CO (p = 0.049). Conclusion: Reference values for SOPs in the adult shoulder joint were determined for the first time. Significant gender-specific differences were found for all measured SOPs. In addition, it was seen that for some SOPs, the joint side and the patient’s age has to be taken into account in shoulder diagnostics and surgery. Humeral offset (HO) and glenoidal offset (GO) parameters are important morphological parameters in diagnostics and in therapy for shoulder pathologies. Humeral head preserving surgery remains the current state-of-the-art surgery for younger patients in the case of a fracture ,2. LikewDepending on osteosynthesis or the arthroplasty techniques used, changes in shoulder offset parameters (SOPs) affect postoperative function in different ways . If, forIn contrast, increasing the GO in isolation in reverse shoulder arthroplasty results in better joint rotation and reduces the risk of scapula notching and bony impingement ,16,17,18Furthermore, there is no established measurement method in the current literature for the detection of GO in magnetic resonance imaging (MRI). Computed tomography (CT)-based methods are not directly transferable .From the aforementioned, we conclude that SOPs are important factors for shoulder joint function. In particular, surgical therapy, such as humeral head osteosynthesis or shoulder arthroplasty, can change the SOPs, which can result in functional restrictions. In the current literature, there is no study that analyzes physiological humeral and glenoidal offset in a large, primarily radiologically healthy shoulder using cross-sectional imaging. The present study aims to answer the question of whether there are side-, age- and gender-specific differences in SOPs and whether the changes in SOPs are related to osteoarthritis grades. In addition, we aim to establish a new measurement method for recording GO using MRI. The aim of the present study was to create physiological reference values for the shoulder offset parameters in order to optimize the diagnostics and surgical therapies for shoulder pathologies. Between 2013 and 2021, a total of n = 2629 patients underwent magnetic resonance imaging of the shoulder joint in the Department for Diagnostic and Interventional Radiology at the University Medical Center Goettingen. These MRIs were reviewed retrospectively. After applying inclusion and exclusion criteria, 806 patients were included in the final analysis. The study participants were divided into two age groups (20–50 and >50 years). The study was approved by the local ethics committee (IRB number 17/5/22) and performed in accordance with the principles expressed in the Declaration of Helsinki. Without exception, the evaluated MRIs were taken as a part of routine diagnostics because the patients presented with clinical symptoms. In a standardized manner, all the patients were placed in a shoulder positioning tray on the MRI table. All the MRIs were assessed by a senior radiologist and LEB, MPM, ASAH and TH in order to exclude extended structural injuries or heavy joint degeneration.All the examinations were accessible via PACS (Picture Archiving and Communication System) between 1 January 2013 to 31 December 2021 and were initially included in the study. Out of these, all patients aged 20 years or more were included. All the MRI scans were performed on patients to assess their shoulder joint pathologies. Only the patients with a Kellgren/Lawrence score  <3 were All the patients with fractures, osteonecrosis, dysplasia or tumors were excluded. Similarly, the patients who had undergone osteosynthesis or arthroplasty were excluded. The data did not include patients who had any other implants after shoulder joint preservation surgery. The patients with held humeral head luxation and extensive injuries of the rotator cuff were also excluded. Low-quality MRIs (based on only a few gates), were excluded. In addition, all MRIs with imaging artefacts were ruled out.TM Universal Viewer was used . The osteoarthritis score for each shoulder joint was classified according to the Kellgren/Lawrence . Software from GE Healthcare called Centricitynce  scoringnce .For the side-, age- and gender-specific analyses of HO, GO, LGHO, HAO and CO, a Mann–Whitney U test was used. The Mann–Whitney U test was implemented in order to compare the SJH and SJD groups for all the assessed OPs. In order to detect the possible interrelationships between the different OPs and the patients’ age, a Spearman correlation was set. Intraobserver and interobserver reliabilities were evaluated using intraclass correlation coefficients (ICC). Overall, the means ± standard deviations are stated. The statistical analyses were performed using GraphPad Prism 9.00 , SPSS Statistics software version 27.0  and Microsoft Excel . Significant differences are marked with asterisks  and 351 females (43.87%) were analyzed. The final analysis included 429 right shoulders (53.63%) and 371 left shoulders (46.37%). The mean age of the study population was 50.13 years (±16.01 [age range: 20–89 years]). In total (n = 800), a mean HO of 26.19 (±2.70 [18.8–36.4]) was found. The mean HO in left shoulders (n = 371) was 25.45 (±2.62) and the mean HO in right shoulders was 26.83 (±2.59). For the younger patients , a mean HO of 26.07 (±2.61) was detected, whereas the older patients  had a mean HO of 26.31 (±2.77). The analysis yielded a mean HO of 24.17 (±2.01) in female shoulders (n = 351) and 27.77 (±2.03) in male shoulders.In total, a mean GO of 61.79 (±5.67 [42–81.1]) was found. The mean GO was 60.67 (±5.29) in left shoulders and 62.75 (±5.81) in right shoulders. For the younger age group, a mean GO of 62.13 (±5.41) was detected, whereas the older patients showed a mean GO of 61.47 (±5.89). The analysis yielded a mean GO of 58.14 (±4.52) in female shoulders and 64.64 (±4.78) in male shoulders.In total, a mean LGHO of 54.49 (±4.69 [42.2–66.8]) was found. The mean LGHO was 53.74 (±4.54) in left shoulders and 55.13 (±4.72) in right shoulders. For the younger age group, a mean LGHO of 54.16 (±4.62) was detected, whereas the older patients showed a mean LGHO of 54.79 (±4.73). The analysis yielded a mean LGHO of 50.56 (±3.14) in female shoulders and 57.56 (±3.15) in male shoulders.In total, a mean HAO of 28.17 (±2.82 [12.7–36.3]) was found. The mean HAO on the left shoulder joint was 28.14 (±2.93) and the mean HAO on the right joint side was 28.20 (±2.73). For the younger age group, a mean HAO of 28.17 (±2.80) was detected. The older patients showed a mean HAO of 28.17 (±2.85). The analysis yielded a mean HAO of 26.34 (±2.14) in female shoulders and 29.60 (±2.44) in male shoulders.In total, a mean CO of 16.70 (±3.08 [2.8–27.8]) was found. The mean CO in left shoulders was 16.74 (±3.21) and the mean CO in right shoulders was 16.67 (±2.97). For the younger age group, a mean CO of 16.99 (±2.96) was detected, whereas the older patients showed a mean CO of 16.44 (±3.17). The analysis yielded a mean CO of 15.92 (±2.80) in female shoulders and 17.31 (±3.16) in male shoulders.p < 0.001) in the HO and GO between left  and right  shoulder joints. Similarly, a significantly (p < 0.001) higher mean LGHO was found in right shoulder joints . No side-specific differences were found for HAO (p = 0.609) and CO (p = 0.843). All the results are summarized in There was a significant difference (p = 0.011). The analysis showed a mean CO of 16.99 (±2.96) in patients with an age of 20–50 years and a mean CO of 16.44 (±3.17) in patients aged over 50 years. There were no significant differences for HO (p = 0.363), GO (p = 0.124), LGHO (p = 0.081) and HAO (p = 0.756). These results are summarized in A significant difference was found only for the CO between the age groups , and CO . There were no significant correlations between age and HO (p = 0.134), GO (p = 0.061) or HAO (p = 0.637). The results of the correlation analysis are summarized in The correlation analysis showed weak significant inverse correlations between age and LGHO (rp < 0.001) larger measured values were found in male shoulder joints. The mean HO in female patients was 24.17 (±2.01) and the mean HO in male patients was 27.77 (±2.03). A larger GO was found in male shoulder joints (64.64 [±4.78]) compared to female shoulder joints (58.14 [±4.52]). In addition, there were higher values for mean LGHO and HAO in male shoulder joints  compared to female shoulder joints . There was a mean CO of 17.31 (±3.16) in male shoulder joints and a mean CO of 15.92 (±2.80) in female shoulder joints. These results are summarized in For all SOPs, significantly (p = 0.049) between the mean CO of the SJH group (16.75 [±3.04]) compared to the SJD group (15.09 [±3.92]). The other SOPs showed no significant differences between these two groups . The results are summarized in In this study, 777 (97.13%) patients were graded as KL 0-2 (SJH) and 23 (2.87%) patients were graded as KL 3-4 (SJD). There was a significant difference  resulted. These results are summarized in Shoulder offset parameters are important morphological parameters for diagnostics and therapies for shoulder pathologies ,8,14,23.The analysis of side-specific differences showed significantly higher HO, GO and LGHO measurements on the right joint side compared to the left joint side. To the authors’ knowledge, there is currently no other study that describes the side-dependence of HO, GO and LGHO in a primarily radiologically low osteoarthritis population (97.1%) of native shoulder joints. A possible reason is that 90% of the population is right-handed, and therefore uses the right upper limb more dominantly ,25. HoweAge-dependent differences for the SOPs were not found, except for the CO. In addition, a weak inverse correlation between CO and patient age was found. Taking into account the osteoarthritis-dependent analysis, in which significantly lower measured values for CO were found in the group with a higher grade of osteoarthritis (KL 3-4), the most plausible reason for this is the loss of sphericity of the humeral head. Knowles et al. investigated the morphology of the humeral head between healthy shoulder joints and shoulder joints with osteoarthritis using 150 computer tomographic examinations . They weA weak correlation with patient age was also found for the LGHO. Significant differences between the age groups were not detected, so the correlations are classified as marginal. The analysis revealed significantly higher measurements for all SOPs in the male patients compared to the female patients. The gender-dependency of some parameters of shoulder morphology has already been reported in other studies. For example, Piponov et al. demonstrated a greater glenoid height and diameter in the coronal view for male patients, by retrospectively analyzing 108 shoulder CT scans . SimilarHumeral and glenoid offset parameters are important morphological parameters in diagnostics and therapies for shoulder pathologies ,8. The rA limitation of this study is that no comparisons were made between the MRI scans with related X-ray imaging. This was because many of the patients included in the study were only examined using MRI scans and not X-rays. A comparison between the different modalities seems useful. Therefore, the present study could have made even better comparisons with the results of other authors. In addition, comparisons between the measurements from MRI images and CT scans would be desirable. No biometric data were collected in the study and the retrospective nature of the study does not allow any conclusions to be drawn about the pain intensity of the patients. Further studies with a prospective design are necessary to verify the results of this study. The handedness of the patients was also not surveyed. This could also have an influence on the offset parameters. Studies dedicated to this question would also be of high scientific value. It should be noted that, based on the retrospective study design, no intra-individual bilateral measurements of the shoulder joints were performed. This means that the differences found in the mean values of the SOPs between the left and right shoulder could only be determined inter-individually and, therefore, have to be viewed critically. In order to make a statement about the possible intra-individual side differences for the SOPs, future prospective studies with bilateral joint side analyses should be carried out in order to confirm or revise this observation.In the present study, the MRIs of 800 patients were examined for the first time in order to analyze the physiological reference values for SOPs in a sample of radiologically healthy shoulder joints. The mean values for HO, GO, LGHO, HAO and CO depending on gender, joint side and age were presented. HO, GO and LGHO showed significantly higher mean values on the right joint side. These results indicate that, in clinical practice, the healthy contralateral side cannot be used as a reference for surgical planning. However, further prospective studies are needed to support this thesis. For all offset parameters, significantly higher values were found in males compared to females. The age- and osteoarthritis-dependent analyses rendered significantly lower results for CO in older patients and patients with a higher grade of osteoarthritis, which seems to be caused by the loss of sphericity of the humeral head. These results should be considered in shoulder diagnostics and surgery.


The least age at onset, F:M, RF and anti-CCP positivity were present in Upper Egypt (p < 0.0001), while the highest DAS28 was reported in Canal cities and Sinai (p < 0.0001). The HAQ was significantly increased in Upper Egypt with the least disability in Canal cities and Sinai (p = 0.001). Biologic therapy intake was higher in Lower Egypt followed by the Capital (p < 0.0001). The spectrum of RA phenotype in Egypt is variable across the country with an increasing shift in the F:M ratio. The age at onset was lower than in other countries.To depict the spectrum of rheumatoid arthritis (RA) in Egypt in relation to other universal studies to provide broad-based characteristics to this particular population. This work included 10,364 adult RA patients from 26 specialized Egyptian rheumatology centers representing 22 major cities all over the country. The demographic and clinical features as well as therapeutic data were assessed. The mean age of the patients was 44.8 ± 11.7 years, disease duration 6.4 ± 6 years, and age at onset 38.4 ± 11.6 years; 209 (2%) were juvenile-onset. They were 8750 females and 1614 males (F:M 5.4:1). 8% were diabetic and 11.5% hypertensive. Their disease activity score (DAS28) was 4.4 ± 1.4 and health assessment questionnaire (HAQ) 0.95 ± 0.64. The rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were positive in 73.7% and 66.7% respectively. Methotrexate was the most used treatment (78%) followed by hydroxychloroquine (73.7%) and steroids (71.3%). Biologic therapy was received by 11.6% with a significantly higher frequency by males vs females (15.7% vs 10.9%,  Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease primarily affecting small synovial joints usually symmetrically. Symptoms for more than 6 months establish the diagnosis of RA . An intrAlone the laboratory test for RA cannot confirm a diagnosis that is commonly challenging. A complete clinical approach is necessary to diagnose and avoid debilitating joint damage . Yet, auTo improve the clinical outcome in RA, various therapeutic approaches are required , althougIn the milieu of the restricted information on the epidemiology and treatment patterns of RA across Egypt, the aim of the present study was to present the spectrum of RA in Egypt and compare it to other studies from around the world to provide broad-based characteristics to this particular population.This cross-sectional study included a large cohort of 10,364 adult RA patients (new and existing cases) fulfilling the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria  that werPatients were subjected to full history taking and clinical examination. Juvenile-onset RA (JoRA) cases were considered for those who developed the disease before the age of 18 years. It is noteworthy that co-morbidities or manifestations relied on the records of the files. Presence of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) were determined. The use of medications to treat RA was described. Disease activity score (DAS28)  were ass U tests or analysis of variance (ANOVA). P value < 0.05 was considered significant.Data were collected on a standardized data sheet and stored in an electronic database. Data missing completely at random (MCAR) as for the RF, anti-CCP and anti-nuclear antibody (ANA) positivity was handled by running a complete-case analysis (CCA), where all persons with missing values were excluded from the analysis of this test and imputation was not used. Statistical Package for Social Sciences (SPSS) version 25 was used. Variables were presented as frequencies and percentages or mean and standard deviation. A comparison was done using Chi-square test, Mann Whitneyp = 0.002). Biologic therapy was received by 11.6% with a significantly higher frequency by males vs females . Biologic therapies received were etanercept (30.4%), adalimumab (18.4%), golimumab (14%), rituximab (7.9%), infliximab (3.3%), tofacitinib (1.6%), certolizumab (1%), upadacitinib (0.8%), baricitinib (0.39%), abatacept (0.39%) and undefined (17.8%). Patients also received low dose aspirin (4.6%), colchicine (1.3%) and oral anticoagulants (1.1%).The study included 10,364 RA patients recruited from 22 governorates across Egypt. Their mean age was 44.8 ± 11.7 years. They were 8750 females and 1614 males (F:M 5.4:1). Characteristics of the patients and gender differences are presented in Table p < 0.0001).Certain variables according to the geo-location are presented in Table This cross-sectional study presented the socio-demographic, clinical, and therapeutic profile of 10,364 RA patients recruited across Egypt. In the present work the mean age at onset of RA patients in Egypt was 38 years which was significantly lower in females. The F:M was 5.4:1. The age at onset, gender distribution and disease characteristics of RA patients in countries from different continents were compared to the current study  is a well-known potentially life-threatening complication in RA . The endIn this work, neurological manifestations were reported at a low frequency. The frequencies of depression and anxiety were doubled in early RA than in long-standing disease. RA patients with short disease duration and functional limitation were more likely to suffer from depression and anxiety .In this study, the reported frequency of cardiovascular manifestations was low. However, there is a considerable rise in mortality and morbidity in RA due to cardiovascular disease (CVD). The augmented risk for heart disease is related to disease activity and chronic inflammation with traditional risk factors and RA-related characteristics playing a central role . RA patiIn this work, the RF was positive in 73.7% while the anti-CCP was positive in 66.7%. The frequency of RF was comparable to that from a large Colombian study on 68,247 cases  and to tThere was moderate disability in the present cases as measured by the HAQ. The functional capacity  is a central treatment aspect to consider when the RA therapeutic strategy is personalized . The aveThe medications received by the patients of the current study were diverse. In this study, more males were receiving HCQ and biologic therapy and with a lower disease activity. In early RA, targets can be achieved when the baseline level of diseases activity is low, with male gender and shorter disease duration . In thisAcross the country there was a significant difference in the age at onset, gender distribution, disease activity, RF and anti-CCP positivity. A potential converse causal link between educational accomplishment and the risk of RA has been noticed .National Registries are essential to direct current practice. RA registries in the Middle East and North Africa (MENA) region are rarely presented . On compIn a study from Morocco on 225 RA cases, the age of onset (44 years), F:M (7.1:1), DAS28 (5.2 ± 1), RF positivity (90.5%), anti-CCP positivity (88.8%) were higher than the current findings however, those patients were all receiving biologic therapy .In a study on 300 RA patients from Palestine, treatment with biologic therapy, younger age, having work, higher income, absence of morning stiffness and absence of co-morbidities were significantly associated with better quality of life and less disability . In the In a large RA registry in the UK, of 27,607 patients, 70.6% were female (F:M 2.4:1) and their mean BMI was 27.3 . In a stIn a large nationwide US study, the F:M was 2.4:1. Obesity was present in 15.1%, diabetes in 20.4% and dyslipidemia in 48% .Although this is currently the largest data of RA patients from across Egypt, there is a desperate need for effective and applicable national management strategies and guidelines. It seems that still across the country the diagnostic tests are not strictly considered for all patients. In spite that the medications received are mostly alike among the major cities, there is a disperse intake of biologic therapy being higher along a North to South gradient.In conclusion, the spectrum of RA phenotype in Egypt is variable across the country with an increasing shift in the F:M ratio. The age at onset was lower than in other countries.