The detection of patients with extraprostatic disease (≥pT3) by preoperative mpMRI showed a sensitivity, negative predictive value and accuracy of 65.1%, 51.7% and 67.5%. In addition to the suspicion of extraprostatic disease in mpMRI (≥rT3), 84.5% (n = 56) of patients with ≥rT3 underwent primary nerve-sparing surgery with IFST, resulting in 94.7% (n = 54) of men with at least unilateral nerve-sparing surgery after secondary resection with a positive surgical margin rate related to an IFST of 1.8% (n = 1). Conclusion: Patients with rT3 should not be immediately excluded from nerve-sparing surgery, as by using IFST some of these patients can safely undergo nerve-sparing surgery.Background: We aimed to determine the concordance between the radiologic stage (rT), using multiparametric magnetic resonance imaging (mpMRI), and pathologic stage (pT) in patients with high-risk prostate cancer and its influence on nerve-sparing surgery compared to the use of the intraoperative frozen section technique (IFST). Methods: The concordance between rT and pT and the rates of nerve-sparing surgery and positive surgical margin were assessed for patients with high-risk prostate cancer who underwent radical prostatectomy. Results: The concordance between the rT and pT stages was shown in 66.4% ( Prostate cancer (PCa) is the second leading cause of cancer-related mortality and the most commonly diagnosed malignancy among Western men . HistoriIn addition to oncologic outcomes, optimal functional outcomes, such as continence and potency, are important for patients undergoing radical prostatectomy (RP) for PCa. Functional outcomes can be improved by NSS ,5,6. As Data on 160 consecutive patients with high-risk PCa (according to the D’Amico risk classification), who underwent open or robotic RP between January 2018 and June 2020 at the department of Urology, University Hospital Frankfurt, were prospectively collected. From 1 January 2018, all patients with high-risk PCa routinely underwent mpMRI before open or robotically assisted RP. Moreover, for all patients the risk of ECE was calculated according the nomogram of Steuber et al. .n = 34) with neoadjuvant androgen deprivation therapy and patients (n = 10) with neoadjuvant chemotherapy were excluded from the analysis, resulting in 126 consecutive patients with high-risk PCa who have been included in the current analyses.Due to uncertainties in pathologic evaluation in patients with neoadjuvant therapy, those patients  and written informed consent was obtained from all patients. The approval date was on 29 July 2020.mpMRI of the prostate was either performed during the diagnostic workup or for staging purposes. mpMRI included at least T1-weighted, T2-weighted, diffusion-weighed, and dynamic contrast-enhanced imaging and were either performed at outpatient clinics or within our radiologic department. Final radiologic staging (rT) was based on the TNM classification considering the MRI report of the radiologist describing the extracapsular extension with involvement of the neurovascular bundle, seminal invasion, rectal or vesical invasion .The majority of patients underwent bilateral nerve sparing with the intraoperative frozen section technique (IFST) as previously described ,20. In vDuring RP, the tissue of the prostate adjacent to the neurovascular bundle (NVB) was dissected for frozen section. For anatomic orientation, the inner and outer surgical margins, as well as the apical side, were inked with different colours. In the Department of Pathology, the specimens were cut into 3–4 mm-thick slices and all tissue blocks were embedded in freezing media. Stained in haematoxylin and eosin, six µm cryosections were cut from each block to be reviewed by a dedicated uropathologist. At least one malignant gland should have come into contact with the inked surgical margin to be determined as a positive surgical margin (PSM) . In caseDescriptive statistics included frequencies and proportions for categorical coded variables. Medians and interquartile ranges (IQR) were reported for continuously coded variables. Univariable analysis were performed to compare concordance of tumour stage based on preoperative MRI characteristics (rT) with subsequent pathological stage (pT). Specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) and accuracy of mpMRI in predicting extraprostatic disease were calculated. The effect of radiological extraprostatic disease findings on surgical margin rates after RP was examined by comparing PSM between patients with rT2 or ≥rT3. The statistical software GraphPad Prism 5.02 was used .n = 30) had a preoperative PSA ≥20 ng/mL, 78.6% (n = 99) had a biopsy Gleason score ≥8 and 33.3% (n = 42) a suspicious bilateral DRE finding ≥cT2c. Median BMI was 26.5 kg/m2 and median age was 66.0 years. Surgery was performed either with the use of an open  or robotically assisted approach   .According to the nomogram of Steuber et al., the risk of ECE was predicted with means of 55.9% and 72.8% for patients with rT2 and ≥rT3, respectively. When comparing the nomogram to pT-stages, the risk of ECE was predicted with a mean of 60.1% for patients with a subsequent pT2 stage, with 71.8% for patients with ≥pT3.n = 60) of men were classified as rT2, 30.1% (n = 38) rT3a, 21.4% (n = 27) rT3b and 0.9% (n = 1) a rT4 . No pathologic lymph nodes were seen in 88.1% (n = 111) of patients, whereas 11.9% (n = 15) were suspected to have positive lymph nodes. In the histopathological examination of the specimen, 34.1% (n = 43) had a pT2, 38.9% (n = 49) a pT3a, 23.8% (n = 30) a pT3b and 3.2% (n = 4) a pT4 stage. 78.6% (n = 99) were lymph node negative (pN0), whereas 19.8% (n = 25) were lymph node positive (pN1) and 1.6% (n = 2) were classified as pNx, respectively  and 1.7% (n = 1) of patients with rT2 underwent primary bilateral or unilateral NSS with IFST. Bilateral, unilateral and no nerve sparing—after secondary resection if necessary—were performed in 68.3% (n = 41), 11.7% (n = 13) and 10.0% (n = 6). of these cases. In total, 25.0% (n = 15) of patients with rT2 harboured PSM, whereas 75.0% (n = 45) had negative surgical margins.In total, 90.0% (n = 48) and 12.1% (n = 8) of the patients underwent primary bilateral or unilateral NSS with IFST. After secondary resection, bilateral and unilateral NSS was still possible in 42.9% (n = 24) and 51.8% (n = 29) of those men with ≥rT3, whereas in 5.3% (n = 3) no nerves could be spared. A total of 50% (n = 28) of the patients with ≥rT3 and primary NSS harboured PSM, while 80% of the patients with ≥rT3 and primary non-NSS had PSM  in mpMRI, 72.7% ( had PSM .n = 24) of the patients (area of ductus deferens in 14.3% (n = 4), area of secondary resected NVB in 25% (n = 7), area outside of NVB in 14.8% (n = 4), area outside of primary nerve resection and unilateral NSS in 21.4% (n = 6) and pT4 in 10.7% (n = 3)). In 10.7% (n = 3) of men, the reason for PSM was possibly related to NSS with IFST, as PSM was in the area of the NVB but IFST and final pathology of the specimen of IFST showed NSM. In 3.6% (n = 1) of patients, the area of PSM was related to initial NSM in IFST , as the final pathology results of IFST showed PSM  with locally advanced disease (pT3–4) were understaged by preoperative mpMRI which can result in higher PSM rates when the decision to undergo NSS is solely based on preoperative mpMRI. Moreover, 27.9% (n = 12) of patients that harboured pT2 in the specimen were overstaged to ECE by preoperative mpMRI, which might have led to primary nerve resection, when only relying on mpMRI as a decision-making tool for NSS. These results led to a sensitivity of 65.1% and specificity of 72.1% for detecting tumour stage ≥pT3, with a positive predictive value of 81.8%. Comparing these findings with data reported in the literature, where most of the studies show that more than half of the cases with locally advanced cancer (pT3–4) were not detected in preoperative mpMRI, our results seem to be slightly better [First, of all 83 patients with locally advanced disease (pT3-4), ECE was preoperatively detected in 54 of these patients (65.1%). In other words, 34.9%  of men with ≥ rT3 stage had a negative surgical margin in addition to a nerve-sparing procedure using IFST. Using IFST and after secondary resection, bilateral, unilateral and no nerve sparing were performed in ≥rT3 patients, 42.9% (n = 24), 51.8% (n = 29) and 5.3% (n = 3). Without IFST and relying just on the results of preoperative mpMRI, at least some of these patients with ≥rT3 would not have undergone NSS, possibly resulting in worse functional outcomes such as erectile dysfunction and urinary incontinence [n = 28) of the patients undergoing NSS with IFST showed PSM in their final pathology. As the area where the NVB contacts the prostate is routinely checked by IFST and IFST has a low rate of false-negative results, most of the PSM in patients undergoing IFST are not directly related to nerve-sparing procedure [n = 24) of patients to be unrelated to IFST and NSS, whereas 10.7% (n = 3) remained possibly caused by NSS with IFST and 3.6% (n = 1) was caused by NSS with false-negative IFST and might not be present, if all patients with ≥rT3 directly underwent bilateral resection of NVB. One must take into consideration that PSM is not always directly associated with biochemical recurrence (BCR) or disease progression. With a median follow-up of 48 months, Karl et al. showed that BCR only occurred in 39.7% of patients with at least pT3a and PSM [Third, in our analysis, 50.0% (rocedure ,25,26. L and PSM . As seen and PSM ,21. This and PSM . MoreoveThere are several limitations of our study. First, the inherited limitations of a retrospective analysis of the data are to be mentioned. Nevertheless, all data were collected prospectively. Second, the mpMRIs were interpreted by different radiologists as the mpMRI were made at different institutions. A concern regarding mpMRI is the considerable interobserver variability, as the experience of the reader remains of paramount importance ,29. HowempMRI in patients with high-risk PCa provides essential information on the local tumour spread. Nevertheless, our results indicate that especially sensitivity and NPV for detecting ECE using preoperative mpMRI is low. Therefore, one should not solely rely on mpMRI or the use of a nomogram to predict ECE and decide whether NSS is performed for patients with high-risk PCa, as some patients can safely undergo NSS as represented by the use of IFST even if ECE is suspected in mpMRI.


The impact of intimate partner violence (IPV) can be devastating on women’s psychology. Moreover, IPV may destroy women’s self-esteem and self-identity.To identify sociodemographic characteristics associated with IPV and to assess self-esteem among women victims of IPV.st to August 31st, 2018 including all cases IPV female victims in forensic department at Habib BOURGUIBA University Hospital, Sfax. In addition to epidemiological data, Rosenberg scale were used to assess the victim’s self-esteem.It was a descriptive and analytical study over a period of 03 months from June 1Among 142 female IPV victims, only 60 (22.3%) agreed to answer our questionnaire. Their median age was 33.5 years (27-41 years). Victims did not pass high school in 61.7% of cases and they were unemployed in 53.3% of cases. Most women got married at 23 years-old (20-26). The average length of marriage was 7 years (3-14 years). Bruises and abrasions were the most frequent lesions (58.3% and 56.7% of cases). Rosenberg Scale score’s mean was 28.3 ± 4.3. Self-esteem was low or very low among 70% of victims.Female victims of IPV do not have a specific profile and low self-esteem is quite common among them. Additional research is needed to better understand the extent of the problem and to develop more effective reporting methods.No significant relationships.


A growing body of evidence highlights a disparity in mortality rates for people with intellectual disability (ID) compared with the general population. However, national data for England is lacking. The objective of this study was to provide evidence on mortality rates in people with ID.Patients registered for at least a day during 01/04/10-31/03/14 at a GP practice contributing to the Clinical Practice Research Datalink (CPRD) and consenting to linkage were included. Patients with ID were identified via Read codes. Date and cause of death were identified using linked Office of National Statistics mortality data. Crude mortality rates, life expectancy and indirectly age/sex standardised mortality ratios (SMR) were calculated with 95% confidence intervals (CI), overall, by ICD10 chapter, for frequently occurring causes, and those classified as avoidable.11 million person-years were included (0.5% for patients with ID) and 98,035 deaths occurred (0.7% in patients with ID). The mortality rate for patients with ID was 11.2 per 1,000 population, 1.3 times the rate for those without ID, with an associated SMR of 3.2 (95% CI 2.93.4). Life expectancy was 65.5 years (95% CI 61.969.2)for patients with ID and 85.3 years for those without (95% CI 85.285.4). Mortality rates were higher in patients with ID in all age/sex groups, with larger differences for younger ages. Patients with ID had higher cause-specific mortality rates across all ICD10 chapters, with highest SMRs for congenital malformations , nervous system diseases  and mental disorders . Circulatory deaths were the most frequent, with ischaemic heart disease  and cerebrovascular disease  most prominent. A higher proportion of deaths were classified as avoidable for patients with ID  compared to those without . National English data confirm that patients with ID have higher mortality rates than those without. Mortality rates for patients with ID were higher across all age/sex groups and causes, with almost half of deaths classified as avoidable.


Infection is a devastating complication of endoprosthetic replacement (EPR) in orthopaedic oncology. Surgical treatments include debridement and/or one- or two-stage exchange. This study aims to determine the infection-free survival after surgical treatment for first and recurrent EPR infections and identify the risk factors associated with infection recurrence.This single-centre cohort study included all patients with primary bone sarcomas or metastatic bone disease treated for infected EPR between 2010 and 2020. Variables included soft tissue status using McPherson classification, tumour type, silver coating, chemotherapy, previous surgery and microorganisms identified. Data for all previous infections were collected.Survival analysis, with time to recurrent infection following surgical treatment, was calculated at 1, 2 and 4 years. Cox regression analysis was used to assess the influence of different variables on recurrent infection.The cohort included 99 patients with a median age of 44 years (29–58 IQR) at the time of surgical treatment. The most common diagnoses were osteosarcoma and chondrosarcoma.One hundred and thirty-three surgical treatments for first or subsequent infections were performed. At 2 years of follow-up, overall success rates were as follows: two-stage exchange 55.3%, one-stage exchange 45.5%, DAIR with an exchange of modular components 44.6% and DAIR without exchange of modular components 24.7%.Fifty-one (52%) patients were infection-free at the most recent follow-up. Of the remaining 48 patients, 27 (27%) were on antibiotic suppression and 21 (21%) had undergone amputation.P < 0.001); significantly compromised soft tissue status ; and infections due to Enterococcus spp.. (HR 7.31: 95%CI 2.73–19.52); P = 0.01).Significant risk factors for recurrent infection were the type of surgical treatment, with debridement alone as the highest risk (HR 4.75: 95%CI 2.43–9.30; Two-stage exchange with complete removal of all components where feasible is associated with the lowest risk of recurrent infection. Poor soft tissues and enterococcal infections are associated with higher risks of recurrent infection. Treatment demands an appropriate multidisciplinary approach. Patients should be counselled appropriately about the risk of recurrent infection before embarking on complex treatment. Limb salvage with endoprosthetic replacement (EPR) achieves good functional outcomes in the surgical treatment of musculoskeletal tumours. Infection following EPR is devastating for patients leading to severe pain, poor function, reduced quality of life, and even death –3. DefinThis study assesses the success of surgical treatment of infected EPRs, the microbiological profile of infection and identifies the risk factors associated with recurrent infection. Our aim is to provide clinicians with data to inform decisions about the surgical treatment of infected EPRs based on the experience at our high-volume centre.Patients of all ages treated for infected EPRs at our centre between 2010 and 2020 were included in this study. Patients undergoing primary implantation of an EPR for primary bone tumours (PBT) or metastatic bone disease (MBD) were identified from electronic hospital records and clinical coding.First and recurrent EPR infections were included, and those managed with amputation alone or antibiotic suppression at the first episode of infection were excluded. Electronic patient records were reviewed for information on all previous surgical treatments for infected EPR dating back to the index EPR procedure. For each surgical treatment, the following clinical and microbiological data were collected: details of tumour type and initial prosthesis implanted, history of radiotherapy and chemotherapy, presentation of infection, soft tissue status, infecting organism, surgical treatment and follow-up. The condition of the local soft tissues at the time of surgery was categorised using the staging system proposed by McPherson, which considers the following compromising factors: active infection for longer than 3 months; previous radiotherapy; soft tissue loss; the presence of a fistula or subcutaneous abscess and prior periarticular fracture . The numThe consultant surgeon decided on the choice of surgical treatment often in consultation with colleagues. Patients who had an initial washout to control sepsis before going on to have a definitive surgical treatment for infection were classified under the definitive procedure. The approach to surgery in our centre is to perform a comprehensive debridement and excision of infected and nonviable bone or soft tissues with tissue sampling for microbiological analysis plus or minus implant removal/exchange. Surgical interventions were classified as one-stage; two-stage; debridement, antibiotics, and implant retention (DAIR) with exchange of modular components; DAIR without exchange of modular components; and excision arthroplasty. One-stage procedures involved the exchange of all prosthetic components, whereas two-stage procedures involved the implantation of a spacer and prolonged systemic antibiotic therapy followed by a second-stage implantation of a new prosthesis. Patients intended for a two-stage exchange who had the first-stage but did not undergo a second-stage procedure were categorised as two-stage exchange (without reimplantation). We defined DAIR as debridement and change of modular components with retention of at least one prosthetic stem. DAIR without exchange of modular components did not include a change of any modular components or prosthetic stems but did involve debridement of soft tissues and prolonged systemic antimicrobial therapy. Excision arthroplasty involved the removal of the implant without further reconstruction.The Stanmore METS® (Modular Endoprosthetic Tumour System)  was the most frequently used prosthesis. Some implants incorporated an Agluna® antimicrobial ionic silver surface coating.All patients received 6 to 12 weeks of pathogen-directed systemic antimicrobial treatment based on microbiological culture and sensitivities. Typically, the first 6 weeks were intravenous, with or without an oral adjunct, followed by a switch to oral antibiotics for an intended 12 weeks. Staphylococcal and culture-negative infections were usually treated with teicoplanin for 6 weeks, with the addition of oral rifampicin, followed by an oral switch, most commonly either to doxycycline or ciprofloxacin in combination with rifampicin for 12 weeks. After May 2017, our microbiologists considered exclusively oral antibiotic treatment based on the findings of the OVIVA Trial .We defined recurrent infection as follows: 1. infection with positive cultures of the same or different organisms from periprosthetic samples or an aspirate; 2. wound or sinus drainage recurring or persisting for 3 months beyond the index procedure for infection; or 3. a requirement for further surgery for an infection.P < 0.1) were then included in a multivariate Cox regression analysis. A backwards selection procedure was performed to retain factors associated with the outcome in the final model. Non-significant factors were omitted one at a time until only factors showing an association with the outcome remained. The results of the regression analysis are expressed as hazard ratios with 95% confidence intervals. P values ≤ 0.05 were considered statistically significant. Statistical analysis was performed using SPSS version 25.0 .Descriptive statistics were used to report continuous and categorical variables. Kaplan–Meier survivorship curves with recurrent infection as an endpoint were generated for 1-year, 2-year and 4-year follow-up with 95% confidence intervals (CI). The relationship between variables was investigated using a two-stage process. Firstly, a univariate Cox analysis was performed to analyse the relationship between each factor and recurrent infection. Significant variables  was 44 years (29–58 IQR). Tumour types were osteosarcoma (47), chondrosarcoma (23), Ewing’s sarcoma (7), other soft tissue/bone sarcoma (7), giant cell tumour of bone (7) and metastatic bone disease (8). The median time to the first infection was 6.1 years (IQR 1.6 – 28.5).Of 99 first infections, 4 proceeded with antibiotic suppression, 4 underwent amputation, and 91 received surgical treatment  patients were infection-free at the final follow-up. Of the remaining 48 patients, 27 (27%) were on antibiotic suppression, and 21 (21%) had undergone amputation. Compromising soft tissue factors identified at the time of surgery are shown in Fig. % patientOrganisms were cultured in 91.0% 121 of 133) of infections , Streptococcus spp. , Gram-negative bacilli  and Enterococcus spp. . 9.3%, 8 of 86) were polymicrobial infections.At first infection, monomicrobial infections were most commonly due to coagulase-negative staphylococci , followed by Staphylococcus aureus, 45.8% (11 of 24) and Enterococcus spp. 12.5% (3 of 24). After three or more episodes of infection, most were monomicrobial infections caused by Staphylococcus aureus , Coagulase-negative staphylococci , Gram-negative bacilli  or Enterococcus spp. . 18.1% (2 of 11) were polymicrobial.The infecting organisms changed with an increasing number of recurrent infections. At the second episode of infection, there was a lower proportion of monomicrobial infections caused by coagulase-negative staphylococci, 20.8% (5 of 24) and one streptococcal infection. In comparison, there were proportionately more monomicrobial infections caused by 57.1% (24 of 42) of recurrent infections were due to the same pathogen group, whereas 26.2% (11 of 42) were due to a different organism group. The remaining 16.7% (7 of 42) of recurrent infections had no cultured organisms.Following a one-stage procedure, success rates were 63.6% 95%CI 45.5–81.7) at 12 months, 45.5% (95%CI 36.4–58.8) at 2 years and 36.4% (95%CI 26.0–46.7) at 4 years  at 12 months, 44.6% (95%CI 36.6–52.7) at 2 years and 39.7% (95%CI 32.3–47.0) at 4 years. The corresponding values for DAIRs without exchange of modular components were 32.9% (95%CI 28.0–37.9) at 12 months, 24.7% (95%CI 21.3–28.1) at 2 years and 16.9% (95%CI 14.7–19.2) at 4 years.There was no 30-day EPR infection-related mortality in the cohort.Enterococcus spp.   . Reimplantation with a silver-coated prosthesis did not reduce the risk of further infection  ; P = 0.002; infection due to P < 0.001)); significantly compromised soft tissue status ; infection involving Enterococcus spp. (HR 7.31: 95%CI 2.73–19.52); P = 0.001)  patients , 11. AmoStaphylococcus aureus (12 to 23%), followed by polymicrobial infections (10 to 11%) and streptococci (9 to 10%). There are a small number of first infections with Gram-negative bacilli (3 to 6 per cent), enterococci (3 to 7%) and anaerobes (2 to 4%), but these become more common with subsequent episodes of infection, likely due to selection pressure after successive treatments with surgery and antibiotics. These microorganisms are often resistant to conventional antibiotics and are considered difficult to treat in PJI algorithms [Enterococcus spp.The microorganisms associated with an infected EPR are similar to conventional PJI at first infection. These are predominantly coagulase-negative staphylococci (30 to 43%) and s aureus  to 23%, gorithms . Our datWe defined recurrent infection based on clinical findings regardless of whether the same pathogen was involved. 57% (24 of 42) of recurrent infections involved the same organisms as the preceding episode, suggesting that these represented relapses rather than new infections. The high overall relapse rate likely reflects the difficulty associated with two-stage exchange after EPR surgery, when the use of custom and very large implants makes the removal of an implant and the use of a spacer challenging.Although silver-coated EPRs may have an antimicrobial effect, we did not find a reduction in the risk of recurrent infection, which is consistent with other studies .When a second-stage reimplantation was performed, two-stage exchange had the highest success rates . Our results are comparable to others which report success rates of 63 to 100% . The autA one-stage exchange avoids the use of a spacer and is therefore attractive. Algorithms for revision arthroplasty recommend that one-stage exchange can be considered in early or low-grade infections with good soft tissue coverage and caused by pathogens sensitive to biofilm active antimicrobials , 13. In DAIR may be an attractive choice for well-fixed or custom, particularly joint-sparing implants. Success rates in PJI range from 50 to 70% in selected cases when specific criteria are met , 13. TheDAIRs without exchange of modular components, when attempted as a definitive procedure for infection, were associated with the highest infection recurrence rate, of over 70% at 2 years. Although debridement may provide source control for sepsis, it is unlikely to eradicate infection and should not be considered a definitive treatment.Our overall success rates are lower than published studies, which seldom include a large sample of salvage procedures and multiply treated EPRs , 6, 9. WOur findings have implications for the provision of services for patients with EPR infections. We recommend that patients be promptly assessed and investigated for a microbiological diagnosis and optimisation of soft tissues as part of an infection MDT before deciding on treatment intent.Our study benefits from a relatively large cohort with long follow-up. All patients were included in the cohort, and none were lost to follow-up, minimising the risk of selection bias. Although a relatively large sample, this is a heterogeneous population undergoing a range of procedures for a wide range of conditions and our study is too small to detect small effects on outcome. Although the effect of confounding variables was considered, our study was retrospective which increases the possibility of unmeasured confounders.Enterococcus spp. are independent risk factors for recurrent infection after treatment. A two-stage exchange is the most successful procedure for eradicating infection. The overall success rate after one-stage exchange is limited by the high frequency of local soft tissue compromise. Debridement may control sepsis but is not a definitive treatment for infection. DAIR procedures vary significantly and are difficult to define in relation to massive EPRs. Identification of risk factors, timely assessment and a multidisciplinary approach should be available to manage these complex infections. Larger studies are needed to identify microbiological and surgical factors associated with the success of surgical treatment in orthopaedic oncology.Infected EPR remains a significant challenge in orthopaedic oncology. Prior surgical treatment for infection, poor soft tissue status and infection with


Child sexual abuse is a major public health problem in Sri Lanka, with prevalence rates ranging from 14-44%.We aimed to describe the victim and perpetrator characteristics, pattern of disclosure and psychological consequences of sexual abuse in children presenting to a tertiary care hospital in Sri Lanka.This was a retrospective file review study of 164 victims who presented to a Teaching Hospital in Colombo, Sri Lanka, with alleged sexual abuse over a period of 5 years from 2015-2019.Majority of the victims were female and older than 12 years. Majority (73.6%) have been subjected to penetrative sexual abuse with 58.5% of victims reporting more than one incident of abuse. Almost all (99.9%) of the perpetrators were male, with 94.5% being known to the child. Only 42.7% (n=70) of the children revealed about the incident within the first week. Delayed disclosure (i.e. more than 1 week since the incident) was significantly higher in penetrative abuse (p<0.01), multiple incidents of abuse (p<0.01) and in abuse by a known person (p<0.05). Children who disclosed after one week were significantly less likely to disclose about the incident spontaneously (p<0.01). Psychological sequel was seen in 28.7%, with depression being the commonest diagnosis (8.5%). Psychological consequences were significantly in higher those who had physical evidence of abuse (p<0.01), delayed (after 1 week) disclosure (p<0.05) and in those who did not disclose spontaneously (p<0.01).The victim and perpetrator characteristics, pattern of disclosure is comparable with previous literature.No significant relationships.


This study evaluated osseointegration in areas grafted with deproteinized bovinebone (DBB) and biphasic ceramic based on hydroxyapatite and beta-tricalciumphosphate (HA/TCP) in rat tibias. Noncritical bone defects were made in thetibias of 28 rats that were randomly assigned to 2 groups: DBB: DBB-filleddefects and HA/TCP: HA/TCP-filled defects. Bone defects were made in the tibiasbilaterally and filled with biomaterials. After 60 days, the implants wereinserted, and the animals were euthanized 15 and 45 days after the implants wereinstalled. Osseointegration was evaluated by biomechanical, microtomographic andhistometric analysis. Implants installed in the defects filled with DBBpresented higher removal torque forces (2.33 ± 0.51 Ncm vs. 1.50 ± 0.54 Ncm) andmineralized tissue volume around implants at 15 days (34.96 ± 3.68 % vs. 25.61 ±2.95 %) and greater bone-implant contact (20.87 ± 8.28 % vs. 11.52 ± 7.42 %) andbone area within implant threads (26.83 ± 12.35 % vs. 11.98 ± 7.56 %) at 45 dayscompared to the measurements of implants in areas grafted with HA/TCP. Implantsinstalled in defects in areas grafted with DBB had a better osseointegrationpattern than implants placed in defects in areas grafted with HA/TCP. The animals were kept in an environment with temperature (21 ±1°C), humidity (65-70%), and controlled light cycles (12 hours). The animals wereoffered water and feed ad libitum. This study was conductedaccording to the ARRIVE protocol for conducting preclinical studies.This study was submitted and approved by the Animal Ethics Committee of UniversidadeFederal de Uberlândia (CEUA: 11/2020). Twenty-eight rats  and the HA/TCPGroup: defect filled with beta-tricalcium phosphate/Hydroxyapatite . A surface-machined implant wasplaced in the bone defects in both groups . Eachcage allocated 3-4 four animals and the randomization were performed by lot,separating each cage for a specific group using the random.org site.The animals were anesthetized by a combination of ketamine  at a dosage of 0.08 ml/100 g body mass with xylazine at a dosage of 0.04 ml/100 g bodymass. Subsequently, the animals underwent a trichotomy of the internal region ofthe right and left hind paws, and antisepsis was performed.An approximately 10-mm incision was made in planes over the tibial tuberosity.After delicate dissection, the bone tissue was submitted to osteotomy by meansof a countermounted spherical drill with the aid of a 1200 rpm electric motor under abundant solution irrigationwith sterile saline. Each defect that was formed had final measurements of 4 mmin length and width and 1.5 mm in depth; defects were later filled withbiomaterials. The defects were measured with the aid of a periodontal probe. The tissue was sutured byplanes internally with 5.0 resorbable thread  and externally with 4.0 silk thread. The animalsreceived a single dose of streptomycin-associated penicillin at a dosage of 0.1ml/kg  and0.1 ml/kg ketoprofen intramuscularly.After a period of 60 days, a second surgical intervention was performed in theregion that received the biomaterials for implant placement. An incision similarto the first procedure was made over the tibial tuberosity. The grafted regionwas prepared for implant placement by applying a progressive sequence of drills toaccommodate a machined surface implant 4 mm high and 2.2 mm in diameter. All drilling was performed with the aid of anelectric motor, adjusted to 1200 rpm, under abundant irrigation with sterilesaline solution. The implant was installed with the aid of a digital key . The tissue suture andthe postoperative drug protocol that was used were similar to those used in thefirst surgery.At 15 and 45 days after the implant implantation surgical procedures, the animalswere euthanized by an administration of a large anesthetic dose. The tibias wereseparated according to the performed analyses. The right tibia was used formicrotomographic and histomorphometric analysis, whereas the left tibia was usedfor biomechanical analysis.After euthanasia, the left tibias were stabilized with a small splint. Ahexagonal wrench was attached to both the implant and torque wrench , and counterclockwise movement was performed tounscrew the implant. The maximum peak required to move the implant was noted asthe removal torque value.3. The images were reconstructed,spatially repositioned and analyzed by specific software . The region of interest (ROI) was defined as a0.5 mm circular region around the entire diameter of the implant. This ROI wasdefined as the total volume (0.5 mm margin around implants - 4.5 mm x 3.2 mm).As the implants placed did not receive a cover screw in some cases, boneformation occurred inside the prosthetic platform. To prevent this boneformation from interfering with the analysis of the volume of mineralized tissuearound the implant, a second ROI was defined to exclude the platform volume.With the results obtained in both ROIs, it was possible to define the boneformation volume using the formula Total volume - Platform volume = Volume ofmineralized tissues  with the following parameters: camera pixel, 12.45; X-raytube power, 65 kVP; X-ray intensity, 385 µA; integration time, 300 ms; filter,Al-1 mm; and voxel size, 18 µm tissues . ThethrAfter scanning, the right tibias were dehydrated in an increasing series ofethanols (60 - 100%), infiltrated and polymerized into light-curable resin. Theblocks containing the implant and bone tissue were cut at a central point usinga wear and tear system . The finalsections were approximately 45-μm thick, stained with Stevenel's blue associatedwith acid fuchsin and analyzed under an optical microscope  at 100X magnification.Histomorphometric evaluation was performed using image analysis software. The percentages of bone-implant contact (% BIC)and bone area between implant turns (% BBT) were evaluated separately in thefirst six implant casts. A blinded and trained examiner performed theseanalyses.GraphPad Prism 6 software  was used to perform thestatistical analysis in this study. The data generated by the histometric,microtomographic and biomechanical analyses were numerical; thus, these datawere submitted to the Shapiro-Wilk normality test to evaluate if the data weredistributed according to the central distribution theorem. Biomechanical datawere not distributed according to normality, and the nonparametric Mann-Whitneytest was used for the inferential analysis. Data from the microtomographic andhistometric analyses presented a normal distribution, and then these data wereanalyzed using the parametric unpaired t-test. All tests in this study wereconducted with a significance level of 95%.All animals survived after the surgical procedures and were healthy throughout theexperimental period. The sample size calculation was referenced to % BIC data from aprevious study that evaluated the effect of implant surface osseointegration ingrated areas in a similar experimental model and assessment as performed in thisstudy Biomechanical analysis verified that implants placed in DBB-grafted areaspresented greater removal countertorque values than implants placed inHA/TCP-grafted areas within 15 days (2.33 ± 0.51 Ncm vs. 1.50 ± 0.54 Ncm) (p<0.05) .Microtomographic analysis verified that implants installed in DBB-grafted areaspresented higher BV/TV values than implants installed in HA/TCP-grafted areas atthe 15-day (34.96 ± 3.68 % vs. 25.61 ± 2.95 %) (p <0.01) .Histometric analysis verified that implants installed in DBB-grafted areaspresented higher % (20.87 ± 8.28 % vs. 11.52 ± 7.42 %) and % BBT (26.83 ± 12.35% vs. 11.98 ± 7.56 %) values than implants installed in HA/TCP-grafted areasat the 45-day evaluation (p <0.001) . Figure In general, it was found in this study that implants installed in DBB-grafted areaspresented higher values of removal torque and volume of mineralized tissues after 15days and higher % BIC and % BBT at the 45-day evaluation compared with implantsplaced in grafted areas with HA/TCP. These findings may imply that the appropriatetimes for occlusal loading on implants placed in grafted areas with differentosteoconductive biomaterials should be different, especially if the implants did notobtain the primary stability required for immediate loading. These outcomesconflicts with a finding of the previous pre-clinical study in a dog model thatshowed that the immediate and staged implants placed in areas grafted with DBB andHA/TCP presented the same level of osseointegration. However, the longerexperimental period of evaluation (8 weeks) and the different pre-clinical modelsmay be the reason of the differences of the outcomes of our study with this previewstudy ,Increased implant removal torque and mineralized tissue volume in earlier periods ofosseointegration in DBB-grafted areas may be related to the lower degree of DBBresorption compared to that of HA/TCP; this lower degree of resorption is associatedwith higher osteoconductive properties of DBB. Indeed, a clinical study showed thatthe amount of DBB and HA/TCP in bone biopsies harvested after 5 months of themaxillary sinus lift procedure was 15.8 ± 2.1% in the HA/TCP group and 21.36 ± 4.83%in the DBB group ,,Another interesting finding of this study was that the implants placed in areasgrafted with DBB presented a higher degree of osseointegration observed at 45 daysthan the implants placed in HA/TCP-grafted areas. This fact may indicate that thedistribution of new bone in the grafted area is even more important than the amountof the new bone, since the areas grafted with DBB presented less or an equal amountof bone formation than the areas grafted with HA/TCP in previous clinical studies,,,Other factors may explain the superiority of osseointegration in implants in areasgrafted with DBB. The experimental model used in this study was a noncritical defectmade on the tibia that would promote the formation of bone in the grafted areas,Despite the important findings of this study, it has some limitations that should betaken into account when analyzing the results. The use of machined implant surfacesis beneficial for purely assessing the effect of biomaterials on theosseointegration process; however, most clinical and preclinical studies evaluatethe osseointegration process in graft areas with surface-modified implants It can be concluded that the implants placed in defects in areas grafted with DBBhave a better osseointegration pattern than implants placed in defects in areasgrafted with HA/TCP.


Pituitary adenoma surgery has evolved rapidly in recent decades. This study aims to determine current practice across a wide range of European neurosurgical centers.  A list of eligible departments performing pituitary adenoma surgery was created. The survey consisted of 58 questions. For analysis, the departments were divided into four subgroups: academic/nonacademic, high-volume/low-volume, “mainly endoscopic/mainly microscopic practice,” and geographical regions.  Data from 254 departments from 34 countries were obtained. In 108 centers (42.5%), <30 pituitary adenomas were operated per year. Twenty (7.9%) centers performed >100 adenoma surgeries per year. Number of neurosurgeons performing endonasal surgeries are as follows: 1 in 24.9% of centers and 2 in 49.8% of centers. All residents assisted endonasal surgeries in 126 centers (49.8%). In 28 centers (21.1%), all residents performed endonasal surgery under supervision during residency. In 141 centers (56.8%), the endoscopic approach was used in >90% of the surgeries. Regular pituitary board (either weekly or once a month) meetings were held in 147 centers (56.3%). Nonfunctioning adenomas represent >70% of pituitary caseload in 149 centers (58.7%).  In our survey, most centers perform less than 100 surgeries for pituitary adenomas. In most centers, pituitary surgeries are performed by one or two neurosurgeons. Residents have a limited exposure to this type of surgery, and the formal pituitary board is not a standard. Nonfunctioning adenomas make up most of surgically treated adenomas. This study can serve as a benchmark for further analyses of pituitary adenoma centers in Europe. Pituitary adenoma surgery has evolved in recent decades because of the emergence of modern technologies such as the endoscope, neuronavigation, intraoperative magnetic resonance imaging (MRI), and intraoperative computer tomography (CT). These changes reflect a growing shift in clinical practice and bring with it new challenges to the field. There is no clear consensus regarding neurosurgical practice in Europe in the number of centers per country, caseload per center and specialized neurosurgeons, training of young neurosurgeons, etc. We created an international investigational team of neurosurgeons and performed an online survey.Demographics .Treatment of nonfunctioning adenomas.Treatment of hormone-secreting adenomas.Surgical techniques.The goal was to cover as many neurosurgical departments as possible in Europe that perform pituitary adenoma surgery. Each member of the study group approached their national peers with a request to participate in the survey. DN and MM were responsible for countries not covered by the other members of the research group. The study group approached 405 departments with a request to participate on the survey. The request was to complete the survey by the respective departments' chairpersons or pass it to a neurosurgeon in charge of the pituitary program. All questions used in survey are presented as supplementary data. The target was to get one completed survey per department. The survey consisted of 58 questions, which could be divided into sections:The study team was composed by neurosurgeons, and questions were answered by neurosurgeons. The study group discussed selection of questions and balance between detailed questions covering the most of pituitary surgery areas. This strategy would lead to excessively long survey with a low response rate. Therefore, the group decided to include only questions which a neurosurgeon should be ready to answer and also decided not to include case discussions. Rather, we focused on more general questions. The study period was from 1 April 2019 to 30 June 2019. This paper analyzed questions on demographics and treatment of nonfunctioning pituitary adenomas (sections A and B). The minimum time to complete the survey was 12 minutes (min) (mean time 18 min). All surveys were completed. Data from 34 European countries were obtained. We failed to obtain answers from five countries .Altogether, 254 European Departments of Neurosurgery completed the survey. Most responses came from Germany (60), Italy (28), France (22), the UK , the CzeAcademic/nonacademic centers (based on participant answers).High-volume/low-volume centers. We defined a high-volume center as >30 pituitary adenoma surgeries per year.Technique applied at the center: “mainly endoscopic” , “mainly microscopic,” and “mixed practice.”Regions: according to the United Nations Statistics Division .A univariate analysis was planned based on the following variables:The study was approved by Ethical Committee of Central Military Hospital, Prague, Czech Republic .α = 0.05. Microsoft Excel and the statistical software SPSS version 25 were used for statistical analyses and data processing.Descriptive statistics were calculated for each survey question. Differences in responses to survey questions based on selected grouping variables were examined using Pearson's chi-square test  with adjusted residuals. The level of statistical significance was set at Altogether, 254 centers participated on the survey. Academic centers represent the majority of centers in our survey . Total neurosurgical caseload per center : 64 centers (25.3%) performed 1500 surgeries per year and 55 (21.7%) 2000 surgeries. There were 47 centers (18.6%) that performed <1000 surgeries per year and 30 centers (11.9%) >3000 surgeries per year. Endonasal pituitary adenoma surgery volume per year: 27 centers (10.6%) treated <10 adenomas per year, 81 centers treated 11–30 adenomas per year (31.9%), 75 centers treated 31–50 adenomas per year (29.5%), 51 centers treated 51–100 adenomas per year (20%), and 20 centers (7.9%) treated >100 adenomas per year . All theWe defined a high-volume center if >30 adenomas are surgically treated per year, which was the case in 146 centers (57.5%). The study showed that most adenomas are treated endonasally. More than 10 transcranial surgeries for pituitary adenoma were performed in only 28 centers (11%). Typically, one or two fully trained neurosurgeons performed endonasal surgeries (one in 24.9% of the centers and two in 49.8% of the centers). More than three neurosurgeons are involved in endonasal surgery in 18 centers (7.1%).Concerning endonasal surgery training, the results are as follows: all residents assisted endonasal surgeries in 126 centers (49.8%); half of the residents assisted in 28 centers (11.1%) and 25% assisted in 54 centers (21.3%) during their training . None ofIn 141 centers (56.8%), the endoscopic approach is used in >90% of the surgeries . The micNonfunctioning adenomas represent >70% of the pituitary caseload in 149 centers (58.7%), <30% of pituitary cases in 15 centers (5.9%).There was a policy of no patient age limit for adenoma surgery for severe visual deficit due to adenoma in 177 centers (69.7%). No surgery was considered an option in 52 centers (20.5%) if the patient is >90 years old. An age limit of 80 years was reported in 20 centers (7.9%). The data on strategy in the treatment of nonfunctioning adenomas are summarized in Surgery for nonfunctioning adenomas without compression of the chiasm and no hypopituitarism was rarely indicated in 107 centers (42.1%) and seldom or never in 119 centers (46.9%).Surgery for nonfunctioning adenoma compressing the chiasm without a visual field deficit in 70-year-old healthy patients was routinely indicated in 99 centers (39%), rarely in 100 (39.4%) and seldom or never in 54 (21.2%).In the same clinical scenario , surgery was indicated routinely in 183 centers (72%), rarely in 53 (20.9%) and seldom or never in 16 (6.3%).In the same clinical scenario , surgery was indicated routinely in 136 centers (53.5%), rarely in 66 (26%) and almost never or never in 48 (18.9%).Radical resection of a giant adenoma was always the goal of surgery in 28 centers (11%), mostly in 133 (52.4%) and rarely or never in 30 (11.8%). The typical management strategy for a giant nonfunctioning adenoma is endonasal surgery followed by craniotomy if necessary, in 118 centers (46.5%), endonasal partial resection, then watch-and-wait for residual adenomas in 98 centers (38.6%) and craniotomy followed by endonasal surgery if necessary in 26 centers (10.2%). Combined transcranial and endonasal surgery in one session was done in four centers (1.6%).The most typical treatments in asymptomatic residual adenoma on the first follow-up MRI were watch-and-wait in 234 centers (92.1%), upfront reoperation in 9 (3.5%), upfront radiosurgery/radiotherapy in 6 (2.4%), and dopamine agonists in 3 centers (1.2%).p=0,001). More than two fully trained neurosurgeons performed endonasal surgery in 29.1% of the academic centers versus 11.1% in nonacademic centers (p=0.01). In 28.1% of the academic centers and 50% of nonacademic centers, <25% of the residents assisted in endonasal surgery (p=0.01). None of the residents performed endonasal surgery in 48% of the academic centers and 68.5% of the nonacademic centers (p=0.01).Academic centers more often performed >30 pituitary adenoma surgeries per year than nonacademic centers . Surgery for nonfunctioning adenoma compressing the chiasm and no visual field deficit in 70-year-old healthy patients was indicated more often in academic centers . The same pattern was found in asymptomatic nonfunctioning adenoma compressing the chiasm in a 45-year-old healthy female patient .No patient age limit for endonasal surgery of nonfunctioning adenoma resection causing severe visual field deficits was applied in 73.5% of the academic centers compared to 57.7% of the nonacademic (p=0.01). In centers using the endoscopic approach, transcranial pituitary adenoma surgery was performed less often . In centers using endoscopy, an ENT surgeon is more often included in the surgical team . Pituitary board is more often held in centers using endoscopy .In all, 64.8% of the centers that mainly use the endoscopic technique performed >30 pituitary adenoma surgeries per year versus 38.9% centers that primarily use microscopy (p=0.001). Totally, 69.4% of the residents in low-volume centers never performed adenoma surgery; in high-volume centers, 40.4% of the residents never performed adenoma surgery . In 38.9% of the low-volume centers, an ENT doctor is never on the surgical team. An ENT doctor is on the surgical team in 25.3% of the cases in high-volume centers (p=0.001). Pituitary board meetings were held in 71.2% of the high-volume centers versus 36.1% of the low-volume centers (p=0.001).In 38.9% of low-volume centers, only one fully trained neurosurgeon was involved in pituitary surgery. In contrast, in 14.5% of high-volume centers, only one fully trained neurosurgeons took part in pituitary surgery (p=0.01). An ENT doctor was never a member of the surgical team in 45.2% of the western centers; an ENT doctor was on the surgical team in 15.7% in northern centers (p=0.001). Routine pituitary board meetings were held in 67.1% of the northern countries and 23.3% of the centers in eastern countries (p=0.001). There was no age limit for nonfunctioning adenoma resection causing severe visual field deficits in 81.4% of the Western centers and 51.4% of the northern centers (p=0.001). Surgery for nonfunctioning adenoma asymptomatically compressing the chiasm in a 30-year-old healthy woman with maternity plans was almost never indicated in 35.1% of the southern centers and 9.8% of the Western centers (p=0.01).None of the residents performs endonasal surgery under supervision in 72.1% of eastern centers and 38.6% of northern centers . In addition, they more often indicate pituitary surgery of non-functioning adenoma compressing the chiasm without visual field deficit (42.5% versus 26.4%).In all, 64.8% of the centers mostly used the endoscopic technique. Endoscopy is more often used in centers performing >30 pituitary adenoma surgeries per year than in low-volume centers (64.8% versus 38.9%). Younus et al. showed a continuous learning curve of endoscopic skull base surgery even after 1000 cases . The leaIn high-volume centers, residents are more often included in pituitary surgery (40.4% versus 69.4%). The pituitary board was mostly held in high-volume centers (71.2% versus 36.1% in low-volume centers).In eastern countries, residents less often participate in pituitary surgery compared to northern countries. In northern countries, ENT doctors are more often a surgical team member than in western countries (45.2% versus 15.7%). The routine pituitary board is more frequent in northern than eastern countries (67.1% versus 23.3%).The main limitations of our study are related to study design. Every survey suffers from sampling bias that largely depends on the response rate. The strength of our survey is the large sample of data with a high response rate and 100% completion rate. It should be emphasized that each respondent in our survey represents one neurosurgical center.The most centers included in our survey cannot be considered as high-volume centers. In most centers, one or two neurosurgeons perform all the pituitary adenoma surgeries. We also found that residents gain limited exposure to this type of surgery. Surprisingly, the formal pituitary board is not a standard. The involvement of an ENT doctor in pituitary surgery is limited. Nonfunctioning adenomas represent most of treated adenomas in most centers. Differences in pituitary adenoma practice were observed between low-volume centers, centers using endoscopy or microscopy, academic and nonacademic centers and regions in Europe. This study may serve as a benchmark for further analyses of pituitary adenoma centers in Europe and as a recommendation to centralize pituitary adenoma care.


Five independent researchers measured the hip angles and the mean values were used to build a database. Results: No differences between groups in sex distribution and BMI were detected. Less coverage of the head (extrusion index), higher Tönnis angle, lower Wiberg and alpha angles characterized early OA hips. These differences increased with age, being greater between group 2 and group 3 (p < 0.01). However, significant differences were still present in the comparison between group 1 and group 2 (p < 0.01)). No differences were detected between group 2 and group 3. Conclusion: Elevated acetabular angle, head extrusion and decreased Wiberg angle characterize hip osteoarthritis at younger ages and should be the focus of hip preservation surgery in terms of osteoarthritis prevention. Pincer-type FAI (higher Wiberg and lower Tönnis angle) and higher alpha angle (CAM) are correlated with the development of later OA. These results shed doubt on applying the hip preservation surgery concept in terms of osteoarthritis prevention in FAI, especially in Pincer-type FAI patients.Objective: The aim of the study is to describe the morphology associated with the development of osteoarthritis (OA) in three different age groups. These data will contribute to defining the morphology associated with early and late hip OA. Methods: We studied 400 hips in 377 patients who had undergone primary THA due to idiopathic OA. Three groups were compared: group 1 ( Hip preservation surgery (HPS) has grown in popularity in the last three decades. The procedures associated with HPS are focused on the correction of the anatomic morphology that has been claimed to lead to osteoarthritis (OA) in order to avoid hip arthroplasty. This mechanical paradigm has been postulated for many years ,3,4,5,6.Although some previous descriptions existed previously, the concept of FAI was coined by Myers et al. in 1999, and was suggested by Ganz as being the underlying cause of early idiopathic hip OA in 2003. There are three types of FAI. CAM-type FAI involves a hump in the transition area between the femoral head and the neck, so with flexion and rotation of the hip, this hump hits the labrum and the acetabulum. Pincer-type FAI is an overgrowth of the acetabular rim that causes friction against the head of the femur and its cartilage when flexing and rotating the hip. The third type is when CAM-type and Pincer-type deformities appear in the same patient . Figure The presAcetabular dysplasia is characterized by insufficient containment of the femoral head by the acetabulum, with the global femoral head under covered as a result of the insufficient bony containment. Uncorrected symptomatic acetabular dysplasia may increase the risk of functional impairment and degenerative joint disease due to distribution of joint reactive forces across a narrow segment of articular cartilage, associated labral hypertrophy and pathology, bony impingement and capsular attenuation ,17,18,19Our aim is to describe the morphology associated with the development of OA in three different age groups. These data will contribute to defining the morphology associated with early and late hip OA.We report a cross-sectional descriptive study of 400 hips in 377 patients who had undergone primary THA in our institution. We included the first 400 primary THA secondary to idiopathic OA from our database, which includes patients since 2008 . We excluded THA secondary to other etiologies and those with no radiological studies in their medical history.To carry out this study, three groups were evaluated.-n = 147): Group corresponding to younger patients aged 60 or less;Group 1 (-n = 155): Group corresponding to patients aged between 61 and 74 years;Group 2 (-n = 98): Group corresponding to elderly patients aged 75 years or more.Group 3  angle is the angle formed by the anatomical axis of the femur and the axis of the femoral neck. An angle <125° is known as Coxa vara.The Tonnïs angle, or acetabular index, is formed by a line connecting the two ends of the acetabular sourcil and the horizontal line of the pelvis . An anglThe lateral center-edge or Wiberg angle is the angle formed by a line drawn through the center of the femoral head and perpendicular to the horizontal line of the pelvis and a line connecting the center of the femoral head and the lateral lip of the acetabulum. Its normal values range from 25° to 40°. If the angle is less than 25°, we can classify this as hip dysplasia .The femoral head extrusion index is defined as the percentage of the femoral head that is not covered by the acetabulum. An extrusion index > 25% is suggestive of hip dysplasia .Sample size calculation: Approximately 32,000 hip arthroplasties are performed in Spain each year. A sample size of 382 patients was required to achieve 95% power, assuming a standard deviation for both groups of 10, and an alpha value of 0.05 (two-sided test).p value < 0.05 was considered statistically significant. All the statistical analyses were performed using SPSS 21 .Statistical analysis: Data were summarized using means and standard deviations (SD), medians and interquartile ranges and also percentages. The Kolmogorov–Smirnov test was used to test the normality assumption. For comparisons, we used the unpaired ANOVA, with post hoc tests as appropriate. All tests were two-tailed. A p > 0.05).Demographic Data: The sample consisted of 400 hips in 377 patients. Demographic data are summarized in Radiological Analysis : In earlp < 0.01), and between group 1 and group 3, with a mean difference of −14.43 (IC95%: −18.58–(−10.2)); (p < 0.01). No differences were detected between group 2 and group 3 (p = 0.133).The Wiberg Angle was 30.54 (SD:14.63), 41,73 (SD:11.20) and 44.77 (SD: 12.02) for groups 1, 2 and 3, respectively. Wiberg angle differences were present between group 1 and group 2, with a mean difference of −11.39 (IC95%: (−15.034–(−7.75)) (p < 0.01), and between group 1 and group 3 with a mean difference of 8.24 (IC95%: 5.12–11.36) (p < 0.01). No differences were detected between group 2 and group 3 (p = 0.395).The Tönnis angle was 15.35 (SD:8.77), 8.94 (SD:8.63) and 7.11 (SD: 10.57) for groups 1, 2 and 3, respectively. Tönnis angle differences were present between group 1 and group 2 with a mean difference of 6.41 (IC95%: 4.00–9.8) (p < 0.01), and between group 1 and group 3, with a mean difference of 8.23 (IC95%: 4.61–11.85) (p < 0.01). No differences were detected between group 2 and group 3 (p = 0.65).The extrusion index was 22.12 (SD: 4.54); 16.73 (SD: 11.47) and 13.89 (SD: 11.03) for group 1, 2 and 3 respectively. Extrusion index differences were present between group 1 and group 2, with a mean difference of 5.39 (IC95%: 2.12–8.66) (p < 0.01), and between group 1 and group 3, with a mean difference of −11.86 (IC95%: −18.00–(−5.71)) (p < 0.01). No differences were detected between group 2 and group 3 (p = 0.72).The alpha angle was 61.78 (12.87), 71.34 (17.15) and 73.64 (19.46) for groups 1, 2 and 3, respectively. Differences in the alpha angle were present between group 1 and group 2, with a mean difference of −9.55 (IC95%: −14.65–(−4.46)) , 130.60 (8.61) and 130.28 (9.34) for groups 1, 2 and 3, respectively. No differences were detected between groups.Our research correlates the morphology of the hips with the timing of surgical treatment for hip osteoarthritis. These data could help the hip surgeon to consider the morphology that could lead to OA and the value of performing HPS at that level.Higher Wiberg and lower Tonnïs angle and extrusion index have been associated with later OA development and correlate with Pincer-type morphology. One of the objectives of the Pincer-type FAI intervention is to increase the Tonnïs angle and decrease the Wiberg angle. Some authors have reported previously the protective effect of Pincer-type FAI against OA development because of a higher surface and a homogenous distribution of the load ,27,29,30We did not find any association between the CAM-type FAI and the development of early OA. The patients with the highest alpha angle were those who later received surgical treatment. Hartofilakidis et al. reported that the alpha angle did not influence the development of osteoarthritis, being even higher in those cases in which OA did not develop over the 18-year follow-up . In the The association between the development of OA and the CAM-type morphology has been previously described secondary to labrum injury ,33. HoweThere is no evidence of any correlation between CAM-type FAI and hip pain. In an important study of 3202 patients, Gosvig et al. found no correlation between CAM morphology and mechanical groin or hip pain. Accordingly, no correlation between CAM morphology and hip OA was reported . It has The alpha angle was greater in older patients (group 3). Doubts arise about the origin of this morphology, in terms of whether it is congenital or acquired ,47,48. Ip = 0.14), with the direction of the effect favoring the physiotherapy group in terms of hip cartilage metabolism [In this context, surgeons should focus on the real effect of the ostheochondroplasty on cartilage. The Australian FASHIoN RCT, published in 2021, reported some clarifying results about such effects. The data of semi-quantitative MRI analysis demonstrated worse cartilage and labral scores in the arthroscopic group at 12 months in comparison with the physiotherapy group. The dGEMRIC outcome was −59 ms (95% CI. 137.9 to 19.6)  and higher alpha angle (CAM) are correlated with the development of later OA. These results shed doubt on applying the hip preservation surgery concept to osteoarthritis prevention in FAI, especially in Pincer-type FAI patients.


Lymphatic malformations (LMs) are classified as macrocystic, microcystic or mixed. Treatment depends on their characteristics: surgery, sclerotherapy, both combined, systemic treatment or observation. This study aims to analyze the surgical and interventional management of LMs in children over the last two decades in our university hospital.Management of children born with LMs between 2000 and 2019 was reviewed. Parameters collected were: malformation characteristics, type of treatment, symptoms, imaging, timing of diagnosis and first treatment, number of interventions, recovery rate, complications and length of stay.p = 0.04). Symptoms, imaging, timing of diagnosis and first treatment, number of interventions and complications were not statistically significant. Overall, the number of surgeries was lower than sclerotherapies (p = 0.04). Recovery rate after surgery was higher in macrocystic LMs (p = 0.01). Complications and length of stay were not statistically significant.Files of 48 children were reviewed: 27 with macrocystic and 21 with microcystic LMs. There was no statistically significant difference in type of treatment except for combined treatment, more performed in microcystic LMs (A good rate of recovery was observed when surgery was performed, with no significant increase in complications and length of stay. A prospective study will be determinant to create a decisional algorithm for children with LMs. Lymphatic malformations (LMs) are benign vascular anomalies composed of dilated lymphatic channels and cysts that affect between 1/200 and 1/4000 live births, equally distributed among males and females , 4.LMs are classified as macrocystic (cysts measuring more than 2 cm), microcystic (cysts measuring less than 2 cm) or mixed . The indBoth ultrasound and magnetic resonance imaging (MRI) determine the extent of the lesions and the anatomic relationship to the adjacent structures .Several treatment modalities are available such as sclerotherapy, surgery, laser coagulation, radiofrequency and systemic treatment for complex, generalized cases , 6, yet This study aims to compare the surgical and radiological  management of macrocystic and microcystic LMs in children in terms of number of interventions, recovery rate and postinterventional complications. Evolution of treatment over a 20-year period is also reviewed.Demographic and disease-related data of children treated for a lymphatic malformation at Lausanne University Hospital were retrospectively collected from August 2002 to May 2021. Files of children were analyzed according to the type of malformation and its localization. Lesions were classified into macrocystic and microcystic LMs according to the type of cysts predominant (> 50%) inside the lesion, after MRI and/or sonography. Lesions were classified into two groups rather than three  as a result of the limited number of cases included in the study and in order to make a more comprehensible and clearer analysis. Size of the lesions was not taken into account since treatment modality remained unaffected by this characteristic. However, expansion into deeper cavities was considered. Children were categorized into four groups: those treated by surgery, those treated by percutaneous sclerotherapy, those treated by a combination of both and those observed without intervention. All consecutive cases were included in the study.Initial symptoms, imaging, timing of diagnosis , age at first treatment, evolution of treatment over a 20-year period and rate of genetic mutation of PIK3CA were reviewed. Primary endpoints were the number of interventions needed and the response to treatment upon physical examination. Secondary endpoints were based on the rate of postinterventional complications and the length of hospital stay after surgery or sclerotherapy.The inclusion criteria were pediatric patients with superficial  or deep simple LMs, according to the International Society for the Study of Vascular Anomalies (ISSVA) classification , localizPatients regularly meet their surgeon after surgery or interventional treatment at the outpatient clinic of Pediatric Surgery at Lausanne University Hospital. Follow-up lasts for years, as well as for patients being under observation.t-test or nonparametric tests, as appropriate. Statistical analyses were carried out by using Prism version 8.4.3 . All statistical tests were two-sided and a p-value < 0.05 was considered statistically significant. This study was reviewed and approved by the local Commission on Ethics in Human Research .Categorical data were quantified as counts and percentages and compared with the use of the chi-square test. Continuous data were displayed as means and standard deviations (SD) or median with interquartile range according to their normal distribution or not and compared using Student’s Fifty-eight patients were eligible for the study. Eight of them were excluded due to an alternative diagnosis: 2 had gigantism, 2 had lymphedema, 1 had a lymphangiomatosis, 1 had an intra-articular cyst, 1 had an angiolymphoid hyperplasia with eosinophilia and 1 had a lipoma. Two patients were excluded due to incomplete data: 1 patient with macrocystic LM had missing date and type of sclerotherapy and the type of malformation was not reported in the other patient excluded. There was one loss to follow-up for a patient who moved to France after a period of observation.  The patient’s data were considered for analysis, except for follow-up.Files of forty-eight children were analyzed: 27 children in the macrocystic LMs group and 21 in the microcystic LMs group. Patient flow diagram is displayed in Fig. Twenty-four malformations were localized in the cervicofacial area (50%), 11 in the limbs (22.9%), 9 in the thoracic area (18.8%) and 3 in the axilla (6.3%). Localizations of the macrocystic LMs were: 14 in the cervicofacial area (51.9%), 5 in the limbs (18.5%), 6 in the thoracic area (22.2%) and 2 in the axilla (7.4%). Respectively, 11 lesions (52.4%), 6 (28.6%), 3 (14.3%) and 1 (4.8%) in the microcystic LMs group. All but one of the children presented with a superficial lesion, the remaining one having a macrocystic mediastinal LM.p = 0.42). Two patients in the macrocystic LMs group  and 1 patient in the microcystic LMs group underwent sclerotherapy alone, representing 7.4% and 4.8%, respectively (p = 0.71). A combination of both treatments was administered to 1 patient (3.7%) and 5 patients (23.8%), respectively (p = 0.04). Observation was carried out in 8 patients (29.6%) with macrocystic LMs and 5 patients (23.8%) with microcystic LMs (p = 0.65). Treatment according to localization is displayed in Table The majority of patients were treated with surgery alone in both groups: 16 in the macrocystic LMs group (59.3%) and 10 in the microcystic LMs group (47.6%) (p = 0.71). One patient in each group presented with fever, respectively, 3.7% and 4.8% (p = 0.86). In the macrocystic LMs group, 1 patient (3.7%) experienced bleeding (in addition to pain), 1 presented with dyspnea and 1 with dysphagia (in addition to fever). All but one of the patients with pain, bleeding, fever, dyspnea and dysphagia were surgically treated, one of whom underwent a combined treatment. The remaining patient presented pain and was observed.Each patient included in the study initially presented with swelling. Two patients (7.4%) with macrocystic LMs and 1 patient (4.8%) with microcystic LM had pain (p = 0.41), among whom 36 patients also underwent an MRI . Of these patients, one also underwent a computed tomography (CT). The remaining 3 patients of the study had an MRI alone (3.7% in macrocystic LMs and 9.5% in microcystic LMs).Sonography was used in 45 patients, respectively, 26 patients (96.3%) and 19 patients (90.5%) in macrocystic LMs and microcystic LMs groups (p = 0.04).One (3.7%) macrocystic LM was diagnosed antenatally, against 5 (23.8%) microcystic LMs (p = 0.82). Median age at first treatment was 31 months (IQR 12–65) when surgery alone or as first treatment was used against 20 months (14–22) for sclerotherapy alone or as first treatment (p = 0.75).Macrocystic LMs and microcystic LMs were first treated at a median age of 29 months [interquartile range (IQR) 16–59] and 27 months (16–69), respectively (p = 0.26) to remove the malformation. Mean number of sclerotherapies alone or combined was, respectively, 2.3 (0.6) and 2.8 (1.9) in macrocystic LMs and microcystic LMs (p = 0.58). The mean number of surgeries required was statistically lower than sclerotherapies (1.4 vs. 2.6), regardless of type of malformation (p = 0.04).Macrocystic LMs and microcystic LMs required a mean of 1.3 (SD 0.5) and 1.6 (0.9) surgery alone or combined, respectively,  or partial response .p = 0.06); after surgery alone, disappearance of the lesion in 15 patients (93.8%) with macrocystic LMs and in 5 patients (50%) with microcystic LMs (p = 0.01); after sclerotherapy alone, a disappearance among the 2 patients with macrocystic LMs and the only one with microcystic LM; after combined treatment, a partial disappearance for the only patient with macrocystic LM and a resolution of the malformation for 3 patients (60%) with microcystic LMs (p = 0.27). Observation led to a good evolution  in 3 patients (37.5%) and 1 patient (20%), respectively (p = 0.51).Twenty patients (74.1%) with macrocystic LMs and 10 patients (47.6%) with microcystic LMs presented a resolution of the malformation upon physical examination (p = 0.08). Table Three patients (15.8%) with macrocystic LMs and 6 patients (37.5%) with microcystic LMs encountered complications regardless of the type of treatment (p = 0.37). Clavien–Dindo grade [Postoperative complications rate after surgery alone or combined reached 25% (8 patients out of 32) compared to 11.1% 1 out of 9) postinterventional complications after sclerotherapy alone or combined ( postintep = 0.14). These latter results are displayed in Table Average length of hospital stay was 3 days (SD 4.4) versus 1.3 day (1.2) after surgery and sclerotherapy, respectively (Twenty-eight patients (58.3%) were still followed when the study ended: 13 in the macrocystic LMs group (46.4%) and 15 in the microcystic LMs group (71.4%). One patient was lost to follow-up after moving to France. Among the patients followed, two patients with macrocystic LMs were in treatment when the study ended and none with microcystic LM. The remaining 26 patients were under observation. Most patients whose follow-up ended had been treated with surgery alone , 2 patients (10.5%) had had a combined treatment and 3 patients (15.8%) had been observed. None of them had had sclerotherapy alone. At the completion of the study, the last patient stopped being followed had had surgery 4 years earlier. The other children stopped being followed had had a treatment minimum 9 years earlier.Use of surgical and radiological treatment evolved over this 20-year period. Figure Use of agents for sclerotherapy also evolved over this 20-year period, as shown in Fig. PIK3CA mutation was searched one time and turned out positive in a patient with microcystic LM. This patient had both sclerotherapy and surgery with a partial response.In general practice, no single modality of treatment is effective and multimodal therapy is often necessary, especially in patients with widespread disease and for whom therapeutic options are often palliative . That isPercutaneous sclerotherapy under ultrasound or fluoroscopy is nowadays considered as the first-line treatment of LMs and has a greater success with macrocystic LMs –4, 11–13Many agents have been described, for instance doxycycline, bleomycin, absolute ethanol, betadine, sodium tetradecyl sulfate, polidocanol, OK-432 and alcoholic zein solution , 12, 17.In our study, bleomycin and doxycycline were the most commonly used agents in sclerotherapy, as seen in the literature , 2. BleoIn 2021, after completion of the study, started in our institution the use of polidocanol in foam or liquid form for the treatment of LMs. This molecule is widely described and known to have a low complication rate and a good efficacy profile, as well as a painless injection . Its gooSurgery was the most common treatment given for microcystic LMs in our study, as seen in common practice , 21. It Our results contrast with data found in the literature regarding macrocystic LMs: The majority of these lesions were treated with surgery alone, whereas sclerotherapy is indicated as a first-line treatment in this type of malformation , 10–12. It is pointed that the number of surgeries required was significantly lower compared to the number of sclerotherapies in our institution to achieve recovery, as seen in the literature , 15, 26.®) in spontaneously breathing neonates [Lesions localized in the cervicofacial area can lead to an airway obstruction and dysphagia . Life-thneonates .®) is one of the best-known mTOR inhibitors. Resistant complex lymphatic anomalies with visceral and bony adverse effects have shown good response to Sirolimus® [Recently, mTOR inhibitors showed the promising results in the management of vascular anomalies. mTOR is a serine threonine kinase regulated by phosphoinositide 3 kinase (PI3K) and protein kinase B (Akt) . The PI3rolimus® , 35. A srolimus® .A proposal of treatment algorithm according to malformation type and symptoms based on our data and the data found in the literature is displayed in Fig. The complications rates, their severities and the length of postoperative stay after either surgery or sclerotherapy were not statistically significant, which contrasts with the data found in the literature. Indeed, these latter outcomes have been found higher when surgery is performed compared to sclerotherapy .Complications after surgery include injuries of the facial nerve and hypoglossal nerve, seroma, tissue defects, bleeding, infection, Horner syndrome and development of vesicles on the incision site , 37, 38.Permanent lesions after sclerotherapy for cervicofacial malformations are reported at a rate of 1.2%  . BurrowsSeveral limitations to this study can be identified. First, the study is designed in a retrospective way and is monocentric. Second, a limited sample of patients is included, not allowing to compare the management of malformations according to their localizations. Furthermore, lesions were classified into two groups rather than three  as a result of the limited number of cases included in the study.The statistical robustness regarding the recovery rate is also affected. The head of Plastic Pediatric Surgery department influenced the choice of treatment, leading to a non-use of sclerotherapy for 13 years and a consecutive bias.This study emphasizes the need of a multidisciplinary approach to treat patients with LMs. Indeed, although it is commonly accepted that macrocystic LMs are treated by sclerotherapy, the treatment of microcystic LMs remains debated,and growing evidence shows the efficiency of sclerotherapy to treat these lesions.A prospective study will be a determining factor for the establishment of a treatment algorithm for children with LMs.


Citrus unshiu Marc. cv. Miyagawa-wase) is the most widely cultivated citrus variety in Korea. Although most varieties are imported from Japan, efforts have focused on developing new domestic varieties. We produced mutants by irradiating C. unshiu Marc. cv. Miyagawa-wase scions with gamma rays and grafting them onto C. unshiu Marc. cv. Miyagawa-wase branches. We compared the characteristics of these mutants with Miyagawa-wase fruit as a control. A mutant line named Jedae-unshiu with a unique fruit shape was selected for investigation in detail. The phenotype of Jedae-unshiu fruit demonstrated vertical troughs on the flavedo, smooth albedo without rough protruding fibers, and good adhesion between peel and flesh. In addition, Jedae-unshiu had thicker peels and higher fruit hardness than the control. Higher levels of hesperetin and narirutin, representative flavonoids, accumulated in the peel and flesh of Jedae-unshiu than those of the control. Cellular-level microscopic observations of the mature fruit peels demonstrated epidermal cell disruption in the control but not in Jedae-unshiu. Our results suggest that Jedae-unshiu has high possibility for development as a good storage variety containing large amounts of flavonoids, in addition to potential for ornamental value due to the unique shape of the fruit.Satsuma mandarin ( Citrus unshiu. Early-maturing satsuma mandarin (C. unshiu Marc. cv. Miyagawa-wase) is the most widely cultivated variety of citrus on Jeju Island. Miyagawa wase originated in Fukuoka Prefecture of Japan as a natural mutant of ordinary C. unshiu. This strain was later introduced into Korea by a French priest in 1911 and cultivated as a representative variety. C. unshiu Marc. var. Okitsu, the second-most cultivated citrus variety on Jeju Island, is derived from a branch mutation of C. unshiu Marc. cv. Miyagawa-wase. The cultivation area of C. unshiu Marc. cv. Miyagawa-wase accounts for more than 80% of the total citrus cultivation area on Jeju Island. Most produced citrus fruits are consumed as raw food, and non-commercial-sized fruits are processed into products, such as juice. It is necessary to develop a variety that can not only be consumed raw but also cultivated for ornamental purposes and processed with enhanced functionality :acetic acid [0.05%]) and B (acetonitrile [99.5%]:acetic acid [0.05%]) at a flow rate of 1 mL/min. The gradient profile was programmed at 30% B (0–28 min), 30–80% B (28–33 min), 80% B (33–38 min), 80–30% B (38–43 min), and 30–1% B (43–48 min). The column was equilibrated for 10 min with 30% B before the next injection. The sample injection volume was 10 µL, and flavonoids were detected at 280 nm. The results are expressed as the mean ± standard deviation of three replicates. All statistical analyses were carried out using IBM SPSS software . Significant differences among the samples were calculated using an analysis of variance followed by Duncan’s multiple range test at the 5% level  solution  for 24 h. The fixed tissue was dehydrated and made transparent using the following procedure: 50% ethanol for 5 h; solution I  for 5 h; solution II  for 37 h; solution III  for 5 h; solution IV  for 18 h; solution V  for 5 h; and solution VI  for 5 h. The dehydrated tissues were immediately placed into a carton and covered with paraffin, and the trimmed wax block was fixed on a microtome. The slice thickness was adjusted to 10 µm. The sections were stained as follows: xylene substitute for 60 min and 10 min; a mixture of 100% ethanol and xylene (1:1) for 10 min; 100%, 95%, 85%, and 75% ethanol for 10 min each; 1% safranin for 2 h; 75% ethanol for 5 min; 0.5% fast green for 30 s; 95% and 100% ethanol for 5 min each; a mixture of 100% ethanol and xylene (1:1) for 5 min; and xylene substitute for 10 min twice. The slices were examined and photographed using an optical microscope (Nikon microphoto type 114).The peels of young and mature


The prevalence of overweight and obesity is increasing these days. The adverse effect of obesity can be seen in different physiological functions. Relative fat mass is a newly identified parameter to estimate whole body fat. This study aimed to find out the prevalence of obesity among medical students of a medical college.A descriptive cross-sectional study was carried out among medical students of a medical college from 1 September 2021 to 30 January 2022. Ethical approval was taken from the Institutional Review Committee (Reference number: FNMC/539/078/79). Simple random sampling was done. Height was measured using a stadiometer and waist circumference was measured using non-stretchable tape. Relative fat mass was calculated using the relative fat mass equation. The data was categorised according to the distribution of fat mass. Point estimate and 95% Confidence Interval were calculated.Out of 180 medical students, 57 (31.67%)  were obese according to relative fat mass cut-off. The mean fat mass among male and female participants with high relative fat mass was 27.057±1.42 and 35.674±2.63 respectively.The prevalence of obesity was lower than in other studies done in similar settings. Ethical approval was taken from the Institutional Review Committee of the same institute (Reference number: FNMC/539/078/79). Students studying Bachelor of Medicine, and Bachelor of Surgery (MBBS) during the study period in NMC were included in the study. Informed consent was obtained from the study participants. The sample size was calculated using the following formula:Where,n= minimum required sample sizeZ= 1.96 at 95% Confidence Interval (CI)p= prevalence taken as 50% for maximum sample size calculationq= 1-pe= margin of error, 10%The sample was adjusted for finite population as follows:n' = n / [1+{(n-1) / N}] = 97 / [1+{97-1) / 537}] = 83Where,n'= adjusted sample sizeN= finite population of medical students in National Medical College, 537The calculated minimum required sample size was 83.A simple random sampling technique was used for data collection. A list of 537 medical students was made. The random number was assigned to all the students by using a random number function (RAND) in Microsoft Excel 2013. Then, a total of 180 students were selected from the list.The height of the subjects was measured using a stadiometer and was recorded in centimetres. Waist circumference (WC) was measured with non-stretchable tape in a standing position at the end of expiration at the midpoint of the lower border of the ninth rib and the iliac crest.8RFM was calculated using the formula 64-(20 x heightWC) for males and 76-(20 x heightWC) for females.5 The calculated RFM was classified as essential fat , fitness , average  and obese .Data were then transferred into Excel 2013. Statistical Analysis was done using IBM SPSS Statistics 16.0. Point estimates and 95% CI were calculated.Among 180 medical students, 57 (31.67%)  were obese according to relative fat mass cutoff. Among them 13 (22.81%) males and 44 (77.19%) females were obese according to RFM cut-off. .The mean fat mass among male and female subjects with higher RFM was 27.057±1.42 and 35.674±2.63 respectively. Likewise, the mean waist circumference of male and female subjects with higher RFM was 91.538±5.190 and 76.841±5.70 respectively .9 The study done in a university-affiliated hospital in northern Israel among patients undergoing periodic examinations and in an urban slum of Karachi showed the prevalence of obesity to 83.70% and 89% respectively which is higher than our study.10 In our study, it was found that a greater proportion of obesity was seen in females than males which is similar to the other studies.10 RFM uses a simple model using two anthropometrics height and waist circumference.5 A study done on adult individuals who participated in National Health and Nutrition Examination Survey (NHNES) has validated this model by comparing body fat with dual-energy X-ray absorptiometry (DXA).5Our study showed that about 31.67 % medical students were obese according to RFM cut-off. This finding was slightly lower than the study done on the Korean population which found the prevalence of obesity as around 50%.9 Another study also had similar results where 27.9±5.3 and 40.5±5.9 was the mean RFM among male and female subjects respectively.11 Similarly, a study done on young male adults showed that the mean RFM among subjects with excess body fat was 25.2±3.7.7The mean RFM in our study with high-fat mass was 27.057±1.42 in males and 35.674±2.63 in females. This result was consistent with another study in the Korean adult population where the mean RFM was 23.4±4.5 and 35.6±5.5 in male and female subjects respectively.13 Different studies have shown that RFM correlates better with DXA and bioelectrical impedance (BIA) when compared with BMI.7 Another study showed that RFM had significantly better predictability of cardiometabolic risk compared to BMI.6Obesity is one of the emerging non-communicable diseases that has affected not just the adult population but also children and adolescents. Different studies have been conducted to find a better parameter to determine obesity that can represent the whole population.Our study was not able to show the effectiveness of RFM in predicting obesity-related health issues when compared to other anthropometric parameters like BMI that are widely used. As other parameters were not included in our study it is not possible to comment if this tool is better at predicting different risk factors. Large prospective studies are recommended to reveal the long-term clinical significance of RFM.The prevalence of higher RFM was lower than in other studies done in similar settings. However, body fat mass distribution was on the higher side so the appropriate preventive measures are recommended to prevent the negative consequences of high body fat mass.


Cav2.2 expression is significantly upregulated in breast cancer and its higher expression is inversely correlated with survival suggesting a previously unappreciated role of Cav2.2 in breast cancer. Cav2.2 is required for breast cancer migration, invasion, and metastasis. Interestingly, Cav2.2 promotes invadopodia formation and extracellular matrix (ECM) degradation through the stabilization of invadopodia component cortactin in a proteosome-dependent manner. Moreover, deubiquitinating enzyme USP43 mediated the functions of Cav2.2 in cortactin stabilization, invadopodia formation, ECM degradation, and metastasis. Interestingly, Cav2.2 upregulates USP43 expression through NFAT2 dephosphorylation and nuclear localization. Our study uncovered a novel pathway that regulates cortactin expression and invadopodia formation in breast cancer metastasis.Distant metastasis is the main cause of mortality in breast cancer patients. Using the breast cancer genomic data from The Cancer Genome Atlas (TCGA), we identified brain specific Ca Distant metastasis is the main cause of mortality in breast cancer patients . Patientv2.2 belongs to a voltage-dependent calcium channel family, which is required for maintaining Ca2+ homeostasis in normal cells i was significantly decreased in Cav2.2 knock-down cells  andresults in their nuclear translocation [We then investigated the regulation of USP43 by Cavel Fig. . These rlocation . Nuclearlocation . We thenlocation  (Supplemlocation . To verilocation  and servv2.2 in USP43 regulation. We knocked down NFAT2 expression in Cav2.2 over-expression cells and determined USP43 expressions. NFAT2 knock-down abolished the up-regulation of USP43 levels by Cav2.2 (Fig. v2.2. We next determined the molecular mechanism of NFAT regulation by Cav2.2. Cav2.2 knockdown increased the phosphorylation of NFAT2 and its cytoplasmic localization, while decreased NFAT2 nuclear localization. (Fig. v2.2 is required for the direct regulation of USP43 by NFAT2.We further investigated whether NFAT2 mediates the function of Ca2.2 Fig. A, B. Theon. Fig. . Togethev2.2 in breast cancer metastasis and its underlying mechanism (Fig. v2.2 was required for metastasis by promoting invadopodia formation. Surprisingly deubiquinating enzyme USP43 mediated the function of Cav2.2 in invadopodia formation by stabilizing cortactin, a critical component of invadopodia. Strikingly, Cav2.2 regulates USP43 mRNA and protein levels by activating calcineurin/NFAT2 signaling. To our knowledge, this is the first time calcium channel Cav2.2 and deubiquitination process have been shown to play roles in invadopodia formation. Our study also revealed the functions of deubiquitinase USP43 in breast cancer cell migration, invasion, and metastasis. These studies uncovered a novel pathway that regulated invadopodia formation and metastasis in breast cancer.The functions of calcium channels in tumor metastasis are poorly understood. Our study identified the role of calcium channel Caism Fig. . Cav2.2 v2.2 is exclusively expressed in neuronal tissues but not in breast epithelial cells. The expression of a tissue-specific gene in the cancer of another tissue type presents a unique opportunity for therapy development. For an example, neuronal-specific glutamate receptor GRM1 is aberrantly expressed in melanoma and has been shown to play a critical role in melanoma development. GRM1 inhibitors as therapies for melanoma are currently in clinical trials. Ziconotide is an FDA-approved Cav2.2 blocker for the treatment of severe and chronic pain. It is worthwhile to determine if ziconotide and other N-type calcium channel blockers can be used as therapies for the treatment of breast cancer metastasis. Development of novel Cav2.2 blockers that are not able to cross blood–brain barrier may be even better for the treatment of breast cancer metastasis.CaInvadopodia formation is required for breast cancer cells to degrade extracellular matrix and invade neighboring tissues . Howeverv2.2, NFAT2 and USP43 in invadopodia formation and metastasis. USP43 functions as a deubiquitinase. We have shown that cortactin is a substrate of USP43 in this study. Whether other factors in metastasis are also substrates of USP43 is unknown. The identification of substrates of USP43 that regulate invadopodia formation and metastatic process will improve our knowledge of the roles of ubiquiting process in metastasis. Cortactin regulation is also complex. In addition to the deubiquitination process we identified, it has been shown that phosphorylation can also regulate cortactin activity [Our studies opened up a number of questions regarding the roles of Caactivity , 51. The'previous manuscript for EA onlySupplementary Figure LegendsChecklistSupplementary Figure