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Standard therapy for venous thromboembolism (VTE) includes the use of heparins and vitamin K antagonists. Randomized clinical trials have shown that non-vitamin K oral anticoagulants are as effective and safe as standard therapy in VTE treatment, with an improved pharmacological profile. Edoxaban, a direct inhibitor of factor Xa, has demonstrated noninferiority to standard therapy for the treatment of VTE, preserving a high safety profile even in long-term therapy, in frail patients and in severe clinical presentations. The present paper focuses on the role of edoxaban in VTE treatment, from general population to cancer patients, presenting the available data from randomized clinical trials and real world, to discuss edoxaban use in clinical practice.Lay abstractAnticoagulants are the main treatment for venous thromboembolism (VTE), a condition in which a blood clot forms in the deep veins of the body, in areas such as the leg. Currently, direct oral anticoagulants are available as an alternative to warfarin, a drug that is sensitive to changes in the diet and requires constant monitoring. Direct-oral anticoagulants have been shown in large-scale studies to be as effective and safe as warfarin in the treatment of this disease, with the advantage of not being affected by the food the patient eats. Among these, edoxaban only needs to be taken once a day and has obtained many favorable results in high-risk populations (such as the elderly, patients with cancer, those receiving prolonged treatment or those with severe VTE). In this review we discuss the role of edoxaban for the treatment of VTE in several scenarios and review its role in clinical practice.Tweetable abstractEdoxaban is effective and safe for the treatment of venous thromboembolism (VTE) even in special population. Caution is needed in some patients to avoid major bleeding events. Favorable results are also shown in the ETNA VTE study, a real-world data prospective registry. #edoxaban #VTE #efficacy #safety

Treatment delays in prostate cancer have been characterised, although not explicitly in men undergoing transperineal prostate biopsies. We aimed to determine if delays to radical prostatectomy correlate with adverse outcomes using a contemporary population-based cohort of men diagnosed by transperineal biopsies.This study analysed men with prostate cancer of the International Society for Urological Pathology grade group ≥2, diagnosed by transperineal prostate biopsies who underwent prostatectomy, using the prospectively data from 1 January 2014 to 30 June 2018 Prostate Cancer Outcomes Registry-Victoria. Data were analysed according to stratified demographic and disease characteristics. Time intervals from biopsy (28, 60, 90, 120, and 270 days) were compared using odds ratios and regression analyses for proportion of upgrading, early biochemical recurrence, pT3 disease at prostatectomy, and positive surgical margins.In total, 2008 men were analysed. There were 306 (16.7%) men with upgrading, 151 (8.4%) with biochemical recurrence, 1068 (54.1%) with pT3 disease, and 464 (23.1%) with positive surgical margins (percentages excluded patients with missing data). All adverse outcomes studied were significantly associated with higher prostate-specific antigen and grade at diagnosis. Delays of 120-270 days did not adversely alter the incidence of Gleason upgrading, pT3, or recurrence. Delays (most frequent 60-89 days, 28%) were associated with positive surgical margins but not monotonically. Regression modelling demonstrated no increased likelihood of most adverse outcomes for up to 270 days.Men with prostate cancer of grade group ≥2 diagnosed through transperineal biopsy may wait up to 270 days for a prostatectomy without a greater likelihood of upgrading, pT3 disease, positive surgical margins, or biochemical recurrence.

How the network around ROS protects against oxidative stress and Parkinson’s disease (PD), and how processes at the minutes timescale cause disease and aging after decades, remains enigmatic. Challenging whether the ROS network is as complex as it seems, we built a fairly comprehensive version thereof which we disentangled into a hierarchy of only five simpler subnetworks each delivering one type of robustness. The comprehensive dynamic model described in vitro data sets from two independent laboratories. Notwithstanding its five-fold robustness, it exhibited a relatively sudden breakdown, after some 80 years of virtually steady performance: it predicted aging. PD-related conditions such as lack of DJ-1 protein or increased α-synuclein accelerated the collapse, while antioxidants or caffeine retarded it. Introducing a new concept (aging-time-control coefficient), we found that as many as 25 out of 57 molecular processes controlled aging. We identified new targets for “life-extending interventions”: mitochondrial synthesis, KEAP1 degradation, and p62 metabolism.

Patients with inflammatory bowel disease (IBD) are at increased risk of thrombotic events. Therapies for IBD have the potential to modulate this risk. The aims of this Evidence-Based Guideline were to summarize available evidence and to provide practical recommendations regarding epidemiological aspects, prevention and drug-related risks of venous and arterial thrombotic events in patients with IBD. A virtual meeting took place in May 2020 involving 14 international IBD experts and 3 thrombosis experts from 12 countries. Proposed statements were voted upon in an anonymous manner. Agreement was defined as at least 75% of participants voting as ‘fully agree’ or ‘mostly agree’ with each statement. For each statement, the level of evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) grading system. Consensus was reached for 19 statements. Patients with IBD harbour an increased risk of venous and arterial thrombotic events. Thromboprophylaxis is indicated during hospitalization of any cause in patients with IBD. Disease activity is a modifiable risk factor in patients with IBD, and physicians should aim to achieve deep remission to reduce the risk. Exposure to steroids should be limited. Antitumour necrosis factor agents might be associated with a reduced risk of thrombotic events., Patients with inflammatory bowel disease (IBD) are at increased risk of thrombotic events. This Evidence-Based Guideline presents an international consensus on the prevention of venous and arterial thrombotic events in patients with IBD, and includes 19 recommendations for clinical practice.

In this session several critical issues in diverticular disease were considered, including “It is Symptomatic Diverticular Disease or Irritable Bowel Syndrome?”, “What do determine evolution to diverticulitis, bowel habits alteration or inflammation?”, and “Prevention of acute diverticulitis: Is it at all possible?”. The first talking compared symptoms and laboratory findings between Symptomatic Uncomplicated Diverticular Disease (SUDD) and Irritable Bowel Syndrome (IBS). Although both disease share some symptoms, and although IBS can occur in patients having diverticulosis, SUDD and IBS can be differentiate using a combination of symptoms and laboratory tools. The second talking debated what are the most important risk factors for the evolution towards acute diverticulitis. Current data seem to exclude a significant role of bowel habits alteration, while inflammation seems to have a stronger role, especially in causing acute diverticulitis recurrence. The third talking analyzed about the acute diverticulitis prevention. Primary prevention seem to be little better when using mesalazine, while no definite conclusion can be drawn about the use of fiber and rifaximin. About the secondary prevention, no drugs can be currently advised due to lacking of definite results. At the same time, surgery should be advised on case-by-case basis.

Pulmonic stenosis is a frequent congenital heart disease in dogs, and the treatment of choice is balloon valvuloplasty which is usually safe and successful. The authors describe for the first time a severe complication after balloon valvuloplasty in a five-month-old dog. After effective treatment, with a considerable drop in right ventricular pressures, the dog developed hypoxemia and dyspnea due to pulmonary edema. The dog underwent intensive care and symptoms improved after a few hours of oxygen therapy, continuous positive airway pressure, and furosemide. Although this event is rare, it could have a large impact on patient survival and should be considered in the treatment of severe pulmonary valve stenosis in the future.

INTRODUCTION Endometrial injury (ES) has been suggested as intervention to increase probability of pregnancy in women undergoing assisted reproductive technologies. Majority of studies reported that ES improves outcome in Invitro fertilisation,Intrauterine Insemination(IUI) and natural conceptions: however, the size and quality of studies are poor which questions the presence of any beneficial effect. The present study was done to evaluate the effect of endometrial scratching on pregnancy rate after previous failed Intrauterine Insemination and to assess the pain and bleeding following the procedure. MATERIAL AND METHODS Randomized controlled trial. One hundred sixty-eight women (Eighty-four in each group) with primary/secondary infertility were recruited and randomized into intervention and control group using block randomization. Intervention group underwent ES using pipelle's canula on D8 or D9 of menstrual cycle. Three cycles of ovulation induction with Clomiphene citrate and gonadotrophins followed by IUI was done. The primary end point was clinical pregnancy rate. Pain and bleeding after the procedure were evaluated as secondary outcomes.The study was conducted from June 2017 to June 2019. MAIN RESULTS The cumulative clinical pregnancy rate in ES group was 22.2 % in comparison 9.8 % in control group. In the intent to treat analysis, with a p value of 0.03 calculated from Chi-square test(p

Sydenham's Chorea (SC) is a neuropsychiatric disorder and a major manifestation of acute rheumatic fever. The erroneous assumption that SC is a benign and self-limiting disease, has led to a lack of high-quality scientific evidence of the therapeutical and prognostic features of SC.We retrospectively analyzed the medical records of patients18-years old with SC in 17 Italian pediatric centers. Recorded data included clinical, instrumental and laboratory parameters. Prognostic risk factors including treatment regimens were assessed with univariate and multivariate sub-analysis.We included 171 patients with SC. 66% had generalized chorea, and 34% hemichorea. 81% had carditis (subclinical in 65%). Additional neurological symptoms were reported in 60% of the patients, mainly dysarthria and dysgraphia. 51% had neuropsychiatric symptoms at onset, which persisted after 12 months in 10%. Among psychiatric manifestations, the most common was anxiety disorder/depression (77%). Neurological remission was reached by 93% of the patients at 6 months; 9% relapsed. Patients were treated as follows: 11% penicillin alone, 37% immunomodulatory therapy, 16% symptomatic drugs (i.e. anti-seizure medication, dopamine antagonists) and 37% both symptomatic and immunomodulatory treatment. Neurological outcome did not differ between groups. Patients receiving symptomatic drugs had a higher risk of relapse on multivariate analysis (p = 0.045).Treatment of SC was largely heterogeneous. Based on our results, immunomodulatory therapy did not show higher efficacy at medium term, although it was associated to a slightly lower risk of relapse compared to symptomatic therapy. Longitudinal studies are needed to assess specific risk factors and best treatment options.

OBJECTIVES Translingual neurostimulation (TLNS) studies indicate improved outcomes in neurodegenerative disease or spinal cord injury patients. This study was designed to assess the safety and efficacy of TLNS plus targeted physical therapy (PT) in people with a chronic balance deficit after mild-to-moderate traumatic brain injury (mmTBI). MATERIALS AND METHODS This international, multicenter, randomized study enrolled 122 participants with a chronic balance deficit who had undergone PT following an mmTBI and had plateaued in recovery. Randomized participants received PT plus either high-frequency pulse (HFP; n = 59) or low-frequency pulse (LFP; n = 63) TLNS. The primary efficacy and safety endpoints were the proportion of sensory organization test (SOT) responders (SOT composite score improvement of ≥15 points) and fall frequency after five weeks of treatment, respectively. RESULTS The proportion of SOT responders was significant in the HFP + PT (71.2%) and LFP + PT (63.5%) groups compared with baseline (p

Multiparametric magnetic resonance imaging (MRI) is validated for the detection of clinically significant prostate cancer (csPCa), although patients with negative/equivocal MRI undergo biopsy for false negative concerns. In addition,This trial aimed to determine whether the combination of PSMA + MRI was superior to MRI in diagnostic performance for detecting csPCa.A prospective multicentre phase II imaging trial was conducted. A total of 296 men were enrolled with suspected prostate cancer, with no prior biopsy or MRI, recent MRI (6 mo), and planned transperineal biopsy based on clinical risk and MRI. In all, 291 men underwent MRI, pelvic-only PSMA, and systematic ± targeted biopsy.Sensitivity, specificity, and predictive values (negative predictive value [NPV] and positive predictive value) for csPCa were determined for MRI, PSMA, and PSMA + MRI. PSMA + MRI was defined as negative for PSMA negative Prostate Imaging Reporting and Data System (PI-RADS) 2/3 and positive for either MRI PI-RADS 4/5 or PSMA positive PI-RADS 2/3; csPCa was any International Society of Urological Pathology (ISUP) grade group ≥2 malignancy.Of the patients, 56% (n = 162) had csPCa; 67% had PI-RADS 3-5, 73% were PSMA positive, and 81% were combined PSMA + MRI positive. Combined PSMA + MRI improved NPV compared with MRI alone (91% vs 72%, test ratio = 1.27 [1.11-1.39], p 0.001). Sensitivity also improved (97% vs 83%, p 0.001); however, specificity was reduced (40% vs 53%, p = 0.011). Five csPCa cases were missed with PSMA + MRI (four ISUP 2 and one ISUP 3). Of all men, 19% (56/291) were PSMA + MRI negative (38% of PI-RADS 2/3) and could potentially have avoided biopsy, risking delayed csPCa detection in 3.1% men with csPCa (5/162) or 1.7% (5/291) overall.PSMA + MRI improved NPV and sensitivity for csPCa in an MRI triaged population. Further randomised studies will determine whether biopsy can safely be omitted in men with a high clinical suspicion of csPCa but negative combined imaging.The combination of magnetic resonance imaging (MRI) + prostate-specific membrane antigen positron emission tomography reduces false negatives for clinically significant prostate cancer (csPCa) compared with MRI, potentially allowing a reduction in the number of prostate biopsies required to diagnose csPCa.

Context: Technological advances have improved the toxicities of radiotherapy. We are evaluating the 3D technique in prostate cancer. Materials and Methods: Retrospective study from January 2015 to December 2015 with 29 files. Survival was calculated by Kaplan-Meier method. Results: We collected 29 patient records over the study period. The median age was 75 years with the following extremes: 54 years and 83 years. The median PSA level was 12 ng/ml with a range of 3.05 to 79 ng/ml. Gleason score analysis showed 6 patients (20.69%) with a score of 6 (3 + 3), 23 patients (79.31%) with a score of 7 including 12 patients (41.38%) with grade 3 and 11 patients (37.93%) with grade 4. The median dose delivered was 74 Gy, with a mean dose of 73.79 Gy and extremes of 70 Gy for the minimum and 76 Gy for the maximum. Hormone therapy was combined with radiotherapy in 17 patients (58.62%). Seven patients (24.14%) had grade 1 acute bladder toxicity and one patient (3.45%) had grade 2 acute toxicity. Late bladder toxicity was grade 1 in 5 patients (17.24%), grade 2 in 3 patients (10.34%) and grade 3 in 1 patient (3.45%). Late rectal toxicity, grade 2 in 3 patients (10.34%), grade 3 in 1 patient, was noted. Overall survival at 2 years was 100% and 89.65% at 5 years. Relapse-free survival at 2 years was 82.76% and 62.07% at 5 years. There were 3 deaths (10.34%) of which only one was related to prostate cancer. Conclusion: Radiotherapy, like surgery, is a fundamental option for the treatment of prostate cancers, particularly those that are locally advanced. It is gaining in importance with the improvement of techniques (IMRT, VMAT…) and new fractionations which contribute to the reduction of toxicities and the comfort of patients (shorter spread).

Background: The therapeutic standard for oligoprogressive prostate cancer resistant to castration is second-generation hormone therapy. This systemic treatment is expensive. There are oligoprogressive lesions accessible to radiotherapy. Objectives: To study the impact of radiotherapy of oligoprogressive lesions on the implementation of second generation hormone therapy. Patients and Methods: A retrospective study from 2012 to 2020 was carried out. All patients with oligoprogressive prostate cancer who had received radiotherapy on one or more lesions in progression were collated. Survival was calculated using the Kaplan-Meier method. Results: 8 patients were treated with stereotactic and conformational radiotherapy between August 2012 and August 2020 in the context of oligoprogressive prostate cancer resistant to castration. The median age at diagnosis of oligoprogression was 73 years with a median PSA level of 3.11 ng/ml. Nine lesions were diagnosed with PET scan PSMA. All the lesions were treated by radiotherapy with different regimens. After a median follow-up of 12.5 months, 7 patients showed a biochemical response to treatment with a median decrease in PSA of 67%. The median survival without clinical or biochemical progression was 7 months. The median survival without the need for further systemic treatment was 9 months. During the follow-up period, six patients received second-generation hormone therapy to treat their relapse, and the other two showed no clinical or biochemical relapse. Conclusion: Radiotherapy may be an alternative to delay the introduction of difficult-to-access second-generation hormone therapy in developing countries. A prospective study could validate this therapeutic approach.

Agenesis of pulmonary valve is a rare variant and severe form of Tetralogy of Fallot (ToF). The evolution is usually marked by respiratory and cardiac failure at early age, which needs early surgical correction. Uncorrected treatment of Tetralogy of Fallot diagnosed at adult age is infrequent and only few studies have been described. We present here a rare case of a 22 years old patient who presented with dyspnea since childhood. Subsequent investigations allowed diagnosis of treatment of Tetralogy of Fallot with agenesis of the pulmonary valve. Following the assessment, the patient underwent a surgical repair and the recovery was uneventful. The management of treatment of Tetralogy of Fallot with pulmonary valve agenesis in adult period remains complex, requiring different surgical techniques.

Heart failure is a complex syndrome affecting several organs including kidney, lungs, liver, brain muscles and sympathetic system. Each of these organs might contribute to its severity and prognosis. The prognosis assessment is critical for a correct heart failure management. It has already been demonstrated that a single parameter is weaker for prognosis than different parameters combined. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score has been built and validated for heart failure with reduced ejection fraction (HFrEF) patients by considering cardiopulmonary exercise test data combined with clinical, laboratory and echocardiographic measurements. The betablockers treatment is a milestone in the HFrEF management. In the MECKI score database, the association of betablockers treatment with outcome has been investigated in different settings.

Background and objectives Breast-conserving surgery (BCS) is followed by reoperations in approximately 25%. Reoperations lead to an increased risk of infection and wound healing problems as well as a worse cosmetic outcome. Several technical approaches for an intraoperative margin assessment to decrease the reoperation rate are under evaluation, some of them are still experimental. Methods A prospective single-arm post-marketing study with 60 patients undergoing BCS for ductal carcinoma in situ (DCIS) and invasive breast cancer was conducted. The specimen was intraoperatively examined by the ClearSight™ system, a mobile magnetic resonance imaging system that is based on a diffusion-weighted imaging protocol. However, the results were blinded to the surgeon. Results The ClearSight™ system was performed for both ductal and lobular breast cancer and DCIS, with a sensitivity of 0.80 (95% confidence interval [CI]: 0.44-0.96) and a specificity of 0.84 (95% CI 0.72-0.92), with an overall diagnostic accuracy of 80%. Conclusion Had the ClearSight™ been known to the surgeon intraoperatively, the reoperation rate would have been reduced by 83% for invasive carcinoma, from 10% to 2%, and 50% for DCIS, from 30% to 15% reoperations. A trial designed to examine the impact on reoperation rates is currently ongoing.

The association between hyperuricemia and metabolic syndrome (MS) has been reported in many studies. The authors performed this cross-sectional study to determine the association between hyperuricemia and the MS among diabetic patients in Dakar. Type 2 diabetic patients received as part of their follow-up at the Marc Sankale Center of Abass Ndao Hospital in Dakar were enrolled. For each patient, blood samples and 24 h urine collection were performed. Hyperuricemia was defined for uric acid concentrations > 416 µmol/l in men and > 357 µmol/l in women and the MS was evaluated according to WHO criteria. Statistical analysis was done using the XLSTAT 2019 software. A total of 153 type 2 diabetic patients were included with an average age of 56.63 years. Thirty-one percent (31%) of patients had metabolic syndrome and 32% of them had hyperuricemia. Significant correlations were found between serum uric acid and some components of the MS including triglyceride levels (r = 0.25, p = 0.002), microalbuminuria (r = 0.19, p = 0.018), and fasting glucose (r = - 0.22, p = 0.005). The authors found that hyperuricemia is frequent in patients with MS and this could be considered as a biomarker associated with the presence of this syndrome. Key words: Hyperuricemia, metabolic syndrome, type 2 diabetes, uric acid.

In vitro and ex vivo cultivation of Plasmodium (P) falciparum has facilitated active research into the malaria parasite toward the quest for basic knowledge and the discovery of effective drug treatments. Such a drug discovery program is currently difficult for P. malariae simply because of the absence of in vitro and ex vivo cultivation system for its asexual blood stages supporting antimalarial evaluation. Despite availability of artemisinin combination therapies effective on P. falciparum, P. malariae is being increasingly detected in malaria endemic countries. P. malariae is responsible for chronic infections and is associated with a high burden of anemia and morbidity. Here, we optimized and adapted ex vivo conditions under which P. malariae can be cultured and used for screening antimalarial drugs. Subsequently, this enabled us to test compounds such as artemether, chloroquine, lumefantrine, and quinine for ex vivo antimalarial activity against P. malariae.

Accurate assessment of Gleason grade is essential to guiding prostate cancer management. Not all healthcare systems have universal access to prostate MRI. We investigated whether transperineal (TP) prostate biopsies provide more accurate Gleason grading than transrectal (TR) biopsies in MRI-naive patients. Consecutive patients undergoing TP and TR systematic prostate needle biopsies from 2011 to 2018 were analysed. Patients who underwent radical prostatectomy (RP) within 180 days of biopsies were included. Patients undergoing MRI prior to biopsies were excluded. Pathological concordance, incidence of Gleason upgrading, and correlation coefficients among biopsies and RP Gleason grade were compared. A sub-analysis for concordance in anterior prostate tumours was conducted. 262 patients were included (112 TP; 150 TR), the median age was 63 years, and median time from biopsy to RP was 68 days. Concordance with RP histology for TP was 65% compared to 49% for TR (p = 0.011). Biopsy technique predicted RP concordance independent of the number of cores. Gleason upgrading occurred following 24% of TP versus 33% of TR biopsies. In anterior and apical tumours, upgrading occurred in 19% of TP biopsies and 38% of TR biopsies (p = 0.027). This study suggests TP approach to prostate biopsies result in improved histological grade accuracy in men whom MRI is not available, even after controlling for number of cores. TP approach also resulted in less upgrading for lesions in the anterior and apical prostate compared to TR.

Breast augmentation with implants is a popular cosmetic procedure which has been performed for nearly six decades. As the number of breast augmentation procedures continually rises, we increasingly encounter breast cancer patients who have silicone implants. A significant portion of these patients includes candidates suited for lumpectomy. In these cases, a major concern is the potential exposure of the implant during lumpectomy while an additional consideration is the need to replace the implants due to their age or condition. The purpose of this study is to present an original surgical approach to patients with breast implants requiring breast conservative resection due to breast carcinoma. Over the course of 10 years, breast-augmented candidates for a lumpectomy who underwent a technique that combines lumpectomy with the replacement of the old implant through an incision from the previous scar in the inframammary fold (IMF) were reviewed. With this approach, after removal of the implant through the IMF incision, the tumor is resected with appropriate surgical margins from inside the implant pocket, leaving the overlying skin intact. Data on demographic characteristics, implants, oncologic information, intraoperative surgical findings, and complication were collected. The implant information included brand, size, age, plan of dissection, and condition of the implant as assessed preoperatively. Oncologic information included tumor type, number of tumors, size, and location. Surgical information included the size of the tissue excised, condition of the implant removed, as well as characteristics of the new implants, plane of augmentation, and intraoperative and postoperative complications. All breast specimens were marked and weighed, and the patients were followed-up postoperatively for at least 6 months by the plastic and breast surgeons and by the oncologists. This technique has been employed in 21 patients with previous breast augmentation and a recent diagnosis of breast carcinoma. The average implant age was 13.3 years. The average tumor size was 2.1 cm × 2.8 cm. All patients had clear surgical margins. No significant complications were reported. This technique enables the performing of a lumpectomy procedure without adding additional scars to the breast, the exchange of the implant in a simultaneous procedure, and the decrease of the risk of implant exposure due to additional scars on the breast parenchyma. It minimizes postoperative complications and provides excellent results both therapeutically and aesthetically.

This prospective, controlled, observational cohort study assessed the performance of a novel panel of serum microRNA (miRNA) biomarkers relative to findings on cervical spinal cord magnetic resonance imaging (MRI) in collegiate football players. There were 44 participants included in the study: 30 non-athlete control subjects and 14 male collegiate football athletes participating in a Division I Football Bowl Subdivision of the National Collegiate Athletic Association. Diffuse tensor MRI and blood samples were acquired within the week before the athletic season began and within the week after the last game of the season. All miRNAs were significantly higher in athletes regardless of their fractional anisotropy (FA) values (p

OBJECTIVES: To evaluate the usefulness of radiological re-staging after two and four cycles of neoadjuvant chemotherapy (NAC), the impact of re-staging on further patient management, and the correlation between clinical and final pathological tumour stage at radical cystectomy (RC). PATIENTS AND METHODS: We conducted a longitudinal, single-centre, cohort study of prospectively collected consecutive patients who underwent NAC and RC for urothelial muscle-invasive bladder cancer between July 2001 and December 2017. Patients underwent repeated computed tomography scans for re-staging after two cycles of NAC and after completion of NAC before RC. RESULTS: Of 180 patients, 110 had ≥four cycles of NAC and had complete imaging available. In the entire cohort, further patient management was only changed in 2/180 patients (1.1%) after two cycles of NAC based on radiological findings. Patients who were stable after two cycles but then downstaged after at least four cycles of NAC had a similarly lowered risk of death (hazard ratio [HR] 0.53). Only one patient downstaged after two cycles was subsequently upstaged after four cycles. Clinical downstaging was observed in 51 patients (46%), 55 patients (50%) had no change in clinical stage and four patients (3.6%) were clinically upstaged. Patients clinically downstaged after four cycles of NAC had a lower risk of death (HR 0.49, 95% confidence interval 0.25-0.94; P = 0.033) compared to those with no change or upstaged after completion of NAC. CONCLUSIONS: Re-staging of muscle-invasive bladder cancer after two cycles of NAC offers little additional information, rarely changes patient management, and may therefore be omitted, whereas re-staging after completion of NAC by CT is a strong predictor of overall survival.

Objective Immune checkpoint inhibitors can cause various immune-related adverse events including secondary hypophysitis. We compared clinical characteristics of immunotherapy-induced hypophysitis (IIH) and primary hypophysitis (PH) Design Retrospective multicenter cohort study including 56 patients with IIH and 60 patients with PH. Methods All patients underwent extensive endocrine testing. Data on age, gender, symptoms, endocrine dysfunction, MRI, immunotherapeutic agents and autoimmune diseases were collected. Results Median time of follow-up was 18 months in IIH and 69 months in PH. The median time from initiation of immunotherapy to IIH diagnosis was 3 months. IIH affected males more frequently than PH (p Conclusions Clinically, IIH and PH present with similar symptoms. Diabetes insipidus very rarely occurs in IIH. Central hypocortisolism, in contrast, is a typical feature of IIH. Preexisting autoimmunity seems not to be indicative of developing IIH.

A 54-year-old male presented with a three-year history of bilateral upper eyelid and peri-orbital swelling and adult-onset asthma. Histopathology of a left orbital biopsy showed lymphoid follicles with foamy macrophages and Touton giant cells. Clinical, histological and radiological features were consistent with adult-onset asthma and periocular xanthogranuloma. Treatment with rituximab led to a complete clinical and radiological remission. Nine years later, his condition relapsed with a biopsy of the left orbit and lacrimal gland demonstrating features of IgG4-related disease and adult-onset asthma and periocular xanthogranuloma. Immunohistochemistry showed increased numbers of IgG4+ plasma cells (290 per high power field) and an elevated IgG4+/IgG+ plasma cell ratio of 480%. Involvement by both disorders in the orbit and ocular adnexa of a single patient has not previously been reported in the literature, to the best of our knowledge, and suggests a possible aetiologic or pathophysiologic association.

Patients with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolism (VTE). Alongside the traditional acquired and genetic risk factors for VTE, patients with IBD have pathogenic and clinical peculiarities that are responsible for the increased number of thromboembolic events occurring during their life. A relevant role in modifying this risk in a pro or antithrombotic manner is played by pharmacological therapies and surgery. The availability of several biological agents and small-molecule drugs with different mechanisms of action allows us to also tailor the treatment based on the individual prothrombotic risk to reduce the occurrence of VTE. Available review articles did not provide sufficient and updated knowledge on this topic. Therefore, we assessed the role of each single treatment, including surgery, in modifying the risk of VTE in patients with IBD to provide physicians with recommendations to minimize VTE occurrence. We found that the use of steroids, particularly if prolonged, increased VTE risk, whereas the use of infliximab seemed to reduce such risk. The data relating to the hypothesized prothrombotic risk of tofacitinib were insufficient to draw definitive conclusions. Moreover, surgery has an increased prothrombotic risk. Therefore, implementing measures to prevent VTE, not only with pharmacological prophylaxis but also by reducing patient- and surgery-specific risk factors, is necessary. Our findings confirm the importance of the knowledge of the effect of each single drug or surgery on the overall VTE risk in patients with IBD, even if further data, particularly regarding newer drugs, are needed.

Background Group B streptococcus (GBS) is a leading cause of sepsis, pneumonia and meningitis in infants, with long term neurodevelopmental sequelae. GBS may be associated with poor pregnancy outcomes, including spontaneous abortion, stillbirth and preterm birth. Intrapartum antibiotic prophylaxis (IAP) is currently the only way to prevent early-onset disease (presenting at 0 to 6 days of life), although it has no impact on the disease presenting over 6 days of life and its implementation is challenging in resource poor countries. A maternal vaccine against GBS could reduce all GBS manifestations as well as improve pregnancy outcomes, even in low-income countries. Main body The term “PREPARE” designates an international project aimed at developing a maternal vaccination platform to test vaccines against neonatal GBS infections by maternal immunization. It is a non-profit, multi-center, interventional and experimental study (promoted by the St George University of London. [UK]) with the aim of developing a maternal vaccination platform, determining pregnancy outcomes, and defining the extent of GBS infections in children and mothers in Africa. PREPARE also aims to estimate the protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa and to conduct two trials on candidate GBS vaccines. PREPARE consists of 6 work packages. In four European countries (Italy, UK, Netherlands, France) the recruitment of cases and controls will start in 2020 and will end in 2022. The Italian PREPARE network includes 41 centers. The Italian network aims to collect: GBS isolates from infants with invasive disease, maternal and neonatal sera (cases); cord sera and GBS strains from colonized mothers whose infants do not develop GBS infection (controls). Short conclusion PREPARE will contribute information on protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa. The vaccine that will be tested by the PREPARE study could be an effective strategy to prevent GBS disease.

Background Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is the most serious long-term complication of acute pulmonary embolism (PE) though it is the only potentially reversible form of Pulmonary Hypertension (PH). Its incidence is mainly limited to the first 2 years following the embolic event, however it is often underdiagnosed or misdiagnosed. Methods This is a multicenter observational cross-sectional and prospective study. Patients with a prior diagnosis of PE will be enrolled and undergo baseline evaluation for prevalent PH detection through a clinical examination and an echocardiogram as first screening exam. All cases of intermediate-high echocardiographic probability of PH will be confirmed by right heart catheterization and then identified as CTEPH through appropriate imaging and functional examinations in order to exclude other causes of PH. A CTEPH Risk Score will be created using retrospective data from this prevalent cohort of patients and will be then validated on an incident cohort of patients with acute PE. Results 1000 retrospective and 218 prospective patients are expected to be enrolled and the study is expected to be completed by the end of 2021. Up to now 841 patients (620 retrospective and 221 prospective) have been enrolled. Conclusions This study is the first large prospective study for the prediction of CTEPH development in patients with PE. It aims to create a comprehensive scoring tool that includes echocardiographic data which may allow early detection of CTEPH and the application of targeted follow up screening programs in patients with PE.

The prevalence of chronic pain is between 33% to 64% and is due to cancer pain, but it has also been observed in non-cancer patients. Chronic pain is associated with lower quality of life and higher psychological distress and depressive/anxiety disorders in patients without a history of disorder. In this study we evaluated in clinical practice the effectiveness of the intrathecal pump in 140 patients who underwent pain therapy at our Center. These patients were consecutively enrolled from January 2010 to July 2018. Follow-up was carried out over these eight years regarding the infusion modalities. Pain relief was obtained in 71 (50,7%) patients out of the 140 that experienced satisfactory pain control globally. Intrathecal therapy is one of the best options for chronic severe refractory pain. The greatest advantage of this therapy is due to the possibility of treating the pain with minimal dosages of the drug, avoiding the appearance of troublesome side effects.

Background Despite their lethality and ensuing clinical and therapeutic relevance, circulating tumor cells (CTCs) from colorectal carcinoma (CRC) remain elusive, poorly characterized biological entities. Methods and findings We perfected a cell system of stable, primary lines from human CRC showing that they possess the full complement of ex- and in-vivo, in xenogeneic models, characteristics of CRC stem cells (CCSCs). Here we show how tumor-initiating, CCSCs cells can establish faithful orthotopic phenocopies of the original disease, which contain cells that spread into the circulatory system. While in the vascular bed, these cells retain stemness, thus qualifying as circulating CCSCs (cCCSCs). This is followed by the establishment of lesions in distant organs, which also contain resident metastatic CCSCs (mCCSCs). Interpretation Our results support the concept that throughout all the stages of CRC, stemness is retained as a continuous property by some of their tumor cells. Importantly, we describe a useful standardized model that can enable isolation and stable perpetuation of human CRC's CCSCs, cCCSCs and mCCSCs, providing a useful platform for studies of CRC initiation and progression that is suitable for the discovery of reliable stage-specific biomarkers and the refinement of new patient-tailored therapies. Fund This work was financially supported by grants from "Ministero della Salute Italiano"(GR-2011-02351534, RC1703IC36 and RC1803IC35) to Elena Binda and from "Associazione Italiana Cancro" (IG-14368) Angelo L. Vescovi. None of the above funders have any role in study design, data collection, data analysis, interpretation, writing the project.

Purpose The purpose of the present study was to compare the long-term effectiveness and safety of newly initiated anticoagulation with edoxaban (EDO) versus uninterrupted vitamin K antagonist (VKA) therapy in patients with atrial fibrillation (AF) scheduled for transesophageal echocardiogram (TEE)-guided direct electrical current cardioversion (DCC). Methods A propensity score-matched cohort observational study was performed comparing the safety and effectiveness of edoxaban versus well-controlled VKA therapy among a cohort of consecutive non-valvular AF patients scheduled for DCC. The primary safety outcome was major bleeding. The primary efficacy outcome was the composite of stroke, transient ischemic attack (TIA), and systemic embolism (SE). Findings A total of 130 AF patients receiving edoxaban 60-mg (EDO) treatment were compared with the same number of VKA recipients. The cumulative incidence of major bleedings was 1.54% in the EDO group and 3.08% in the VKA group (P = 0.4). The cumulative incidence of thromboembolic events was 1.54% in the EDO group and 2.31% in the VKA group (P = 0.9). A non-significant trend in improved adherence was observed between the EDO and VKA groups with a total anticoagulant therapy discontinuation rate of 4.62% (6/130) vs 6.15% (8/130), respectively (P = 0.06). Implications Our study provides the evidence of a safe and effective use of edoxaban in this clinical setting, justified by no significant difference in major bleedings and thromboembolic events between edoxaban and well-controlled VKA treatments.

We report the longest follow-up of clinical and biochemical features of two previously reported adult mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients treated with liver transplantation (LT), adding information on a third, recently transplanted, patient. All three patients overcame the early post-operative period and tolerated immunosuppressive therapy. Plasma nucleoside levels dramatically decreased, with evidence of clinical improvement of ambulation and neuropathy. Conversely, other features of MNGIE, as gastrointestinal dysmotility, low weight, ophthalmoparesis, and leukoencephalopathy were essentially unchanged. A similar picture characterized two patients treated with allogenic hematopoietic stem cell transplantation (AHSCT). In conclusion, LT promptly and stably normalizes nucleoside imbalance in MNGIE, stabilizing or improving some clinical parameters with marginal periprocedural mortality rate as compared to AHSCT. Nevertheless, restoring thymidine phosphorylase (TP) activity, achieved by both LT and AHSCT, does not allow a full clinical recovery, probably due to consolidated cellular damage and/or incomplete enzymatic tissue replacement.

Objective Spreading depolarization (SD) is a transient self-propagating wave of neuronal and glial depolarization coupled with large membrane ionic changes and a subsequent depression of neuronal activity. Spreading depolarization in the cortex is implicated in migraine, stroke, and epilepsy. Conversely, spreading depolarization in the striatum, a brain structure deeply involved in motor control and in Parkinson's disease (PD) pathophysiology, has been poorly investigated. Methods We characterized the participation of glutamatergic and dopaminergic transmission in the induction of striatal spreading depolarization by using a novel approach combining optical imaging, measurements of endogenous DA levels, and pharmacological and molecular analyses. Results We found that striatal spreading depolarization requires the concomitant activation of D1-like DA and N-methyl-d-aspartate receptors, and it is reduced in experimental PD. Chronic l-dopa treatment, inducing dyskinesia in the parkinsonian condition, increases the occurrence and speed of propagation of striatal spreading depolarization, which has a direct impact on one of the signaling pathways downstream from the activation of D1 receptors. Conclusion Striatal spreading depolarization might contribute to abnormal basal ganglia activity in the dyskinetic condition and represents a possible therapeutic target. © 2019 International Parkinson and Movement Disorder Society.

Background: Belimumab (Benlysta) is currently approved for the treatment of active Lupus despite standard therapy. Few data are available on the efficacy of this drug in lupus nephritis (LN). Methods: 17 LN female followed in two Nephrology Italian Unit received belimumab for a median period of 36 months (range 6–42 months). The indications were: arthralgia in 3 patients, cutaneous manifestations in 2, residual proteinuria in 8, and the need to reduce steroids for severe side effects in 4. Of interest, 1 patient started therapy during Peritoneal Dialysis and continued after kidney transplantation due to non-responsive arthralgias. Results: Arthralgia and skin manifestations resolved in all patients. Proteinuria normalized in three patients and stabilized in all but one of the others. Steroids were indefinitely stopped in six patients (35%) and reduced to around 40% of the basal dosage in the other patients. During belimumab therapy, three extrarenal and one renal SLE flares were diagnosed accounting for a rate of renal flares of 0.02/patient/year. No major adverse events leading to therapy withdrawal occurred. Clinical case: Arthralgia resolved, immunological parameters improved and prednisone could be reduced within few months in the patient who started belimumab during peritoneal dialysis. After kidney transplantation belimumab was stopped but due to arthralgias unresponsive to standard immunosuppressive therapy it was restarted with success. Conclusions: Belimumab allows the achievement of complete response together with the withdrawal or the reduction of corticosteroids in almost all our patients. Of interest its satisfactory use in a patient in peritoneal dialysis and after kidney transplantation.

We thank Dr Jilani AQ and Dr Sanjay Kumawat for their expert review of this article. We also thank GCE Solutions for overall preparation of the manuscript.

Several theories point to the influence of the geometry of femoral arterial bifurcation in the formation and evolution of atherosclerosis plaques at the level of common, superficial and deep femoral arteries. The objective of this study is to correlate the degrees of calcifications of the femoral tripod with different morphological parameters, namely conicity, tortuosity, proximal and distal diameters of the arteries and angles between the common femoral artery (CFA) and the superficial femoral artery (SFA) and the profound femoral artery (PFA) and the superficial femoral artery. The results showed that only the tortuosity of the common femoral artery influences the formation of atherosclerosis plaque. These results allow us to predict the degree of calcification of the femoral tripod based on the tortuosity of the common femoral artery.

Summary: The diagnosis of venous insufficiency is increasing. Multiple techniques are available for its treatment. Chemical sclerotherapy has been performed for over 70 years. The technique improves lately. Objective: This study was conducted to assess early results of foam sclerotherapy in Senegal. Patients and Methods: This is a prospective and descriptive study conducted from January 1st, 2012 to December 31st, 2015 at cardiovascular center of Fann University hospital in Dakar, Senegal. Foam sclerotherapy was done in 76 patients. Polidocanol was used in concentration of 2%. Sclerotherapy was done several times in patients, every week, as much as needed to occlude varicose veins. We used venous compression in all patients. Results: Foam sclerotherapy sessions permitted to get globally good results. In fact, tight feeling and painful leg disappear in 97% of patients. Decreases of edema were gotten in 97% of patients. For leg ulcer, 64% of complete healing was obtained. The main ulcer healing time was 47 days (18; 72). Some minor complications occurred. No major events, such as deep venous thrombosis or pulmonary embolism, were observed. Conclusion: Foam sclerotherapy is an efficient technique for the treatment of varicose veins of the limbs. Also, it opens good perspectives for vein care.

In Africa, acute rheumatic fever is endemic. Cardiac involvement is one of the most common complications in the form of valvular heart disease representing all damages to the heart valves. It is in this perspective that we realized this study whose general objective was to evaluate the results of mitral repair surgery in children in Senegal and the specific objective was to state the indications for mitral repair surgery and assess the results in terms of morbidity and mortality. This is a retrospective and analytical monocentric study, in the thoracic and cardiovascular surgery department of FANN National University Hospital Center in Dakar. It took place over a period of 30 months. All the patients who underwent mitral surgery, aged less than 18 years were included. The total number of patients was 63, including 39 girls and 24 boys, a sex ratio of 0.62. The average age at the time of the surgery was 12 years old [5 - 17]. The functional symptomatology was dominated by the dyspnea found in all the patients. Cardiac ultrasound was diagnosed with mitral regurgitation in all patients. For all surgical procedures, the approach was a vertical midline sternotomy. The mitral valve was approached by left atriotomy in 40 patients (63.5%) and by transseptal way in 23 patients. All patients had undergone mitral valve repair associated or not with either aortic valve repair in 9 patients (14.2%), aortic valve replacement in 3 patients (4.8%), or one tricuspid valve repair in 31 patients (49%). The average duration of intubation was 6 hours [2 - 52]. The average length of stay in intensive care was 2 days. Postoperative complications have been observed. Surgery was performed in 10 patients with 3 mitral valve replacements, 2 aortic valve replacements, a double mitral and an aortic valve replacement associated with a tricuspid repair and in 4 cases a perfection of their mitral repair. Early and late surgical mortality was zero. The average follow-up time for our patients was 9 months [1 - 26]. During their follow-up, the evolution was favorable in 89% of patients who no longer had any functional symptoms.

BRCA1 and BRCA2 are the most incriminated genes in inherited breast/ovarian cancers. Several pathogenic variants of these genes conferring genetic predisposition have been described in different populations but rarely in sub-Saharan Africa. The objectives of this study were to identify pathogenic variants of the BRCA genes involved in hereditary breast cancer in Senegal and to search for a founder effect. We recruited after free informed consent, 27 unrelated index cases diagnosed with breast cancer and each having a family history. Mutation screening of the genes identified a duplication of ten nucleotides c.815_824dupAGCCATGTGG, (p.Thr276Alafs) (NM_007294.3) located in exon 11 of BRCA1 gene, in 15 index cases (allelic frequency 27.7%). The pathogenic variant has been previously reported in African Americans as a founder mutation of West African origin. Haplotypes analysis of seven microsatellites surrounding the BRCA1 gene highlights a shared haplotype encompassing ~400 kb between D17S855 and D17S1325. This haplotype was not detected in none of 15 healthy controls. Estimation of the age of the pathogenic variant suggested that it occurred ~1400 years ago. Our study identified a founder pathogenic variant of BRCA1 predisposing to breast cancer and enabled the establishment of an affordable genetic test as a mean of prevention for Senegalese women at risk.

ObjectiveTo investigate the predictive value of the Diverticular Inflammation and Complication Assessment (DICA) classification and to develop and validate a combined endoscopic-clinical score predicting clinical outcomes of diverticulosis, named Combined Overview on Diverticular Assessment (CODA).DesignA multicentre, prospective, international cohort study.Setting43 gastroenterology and endoscopy centres located in Europe and South America.Participants2215 patients (2198 completing the study) at the first diagnosis of diverticulosis/diverticular disease were enrolled. Patients were scored according to DICA classifications.InterventionsA 3-year follow-up was performed.Main outcome measuresTo predict the acute diverticulitis and the surgery according to DICA classification. Survival methods for censored observation were used to develop and validate a novel combined endoscopic-clinical score for predicting diverticulitis and surgery (CODA score).ResultsThe 3-year cumulative probability of diverticulitis and surgery was of 3.3% (95% CI 2.5% to 4.5%) in DICA 1, 11.6% (95% CI 9.2% to 14.5%) in DICA 2 and 22.0% (95% CI 17.2% to 28.0%) in DICA 3 (p10% and >2.5% in CODA C, respectively. The CODA score showed optimal discrimination capacity in predicting the risk of surgery in the development (c-statistic: 0.829; 95% CI 0.811 to 0.846) and validation cohort (c-statistic: 0.943; 95% CI 0.905 to 0.981).ConclusionsDICA classification has a significant role in predicting the risk of diverticulitis and surgery in patients with diverticulosis, which is significantly enhanced by the CODA score.Trial registration numberNCT02758860.

Background: Lidocaine hydrochloride is frequently used for management of painful wounds. This prospective, multicentre study examined the effects of 5% lidocaine cream on wound pain relief. Material and methods: The study included 78 patients with painful wounds treated with 5% Lidocaine cream for two weeks in two Italian Hospitals. Patients’ perception of pain was recorded by, using the 5-point Visual Rate Scale and the 11-point Numerical Pain Rating Scale. All medications and adverse events were evaluated in a daily diary. The primary outcome of the study was establishing the wound pain relief based on the results of 5-VRS and pain intensity based on the 11-NPRS testing from baseline to the end of treatment. Clinical aspects and adverse events were also collected. Results: Seventy-eight patients had a median age of 67.5 years (range 18-96 years). 62.8% were women. The wounds included traumatic wounds (n = 39), venous ulcers (n = 25), post-surgical wounds (n = 6) pyoderma gangrenosum (n = 6), vasculitis (n = 1) and pressure ulcer (n = 1). The intensity of pain significantly decreased from the baseline level established at the beginning of treatment (mean score 6.7 − 1.90) - to the level at end of treatment (3.0 − 2.23-; p < 0.0001). 9 patients prematurely stopped the treatment for healing (n = 4), wound improvement (n = 2) and adverse events related to the treatment. (n = 3). 13 patients presented a total of 25 adverse events, 4 of them were related to the treatment. Conclusion: The treatment of painful wounds with 5% Lidocaine Cream for 14 days resulted in reduced pain intensity, and showed high safety and tolerability.

Objective To investigate whether the decrease in dyspnea in neuromuscular diseases after air stacking (AS) occurs mostly in patients with decreased inspiratory muscle force and ensuing chest wall restriction or heterogeneous ventilation across the lungs. Design Interventional, before-after study. Setting A neurorehabilitation inpatient and outpatient center. Participants Fifteen consecutive adult patients affected by neuromuscular diseases (N=15). Interventions AS treatment. Main Outcome Measures Patients had vital capacity (VC) and sniff nasal inspiratory pressure (SNIP) measured. We measured Borg score, oxygen saturation, and ventilation heterogeneity across the lung as estimated from the difference between respiratory resistance at 5 and 19 Hz (R5-19) with the forced oscillation technique before and 5, 30, 60, and 120 minutes after applying AS. Results Before AS, Borg score was significantly related to R5-19 (r2 0.46, P Conclusions These findings suggest that dyspnea in neuromuscular diseases is related to heterogeneous ventilation rather than inspiratory muscle force and/or lung volumes decrease. Restoring ventilation distribution across the lungs with AS appears to improve dyspnea.

Background Using an updated dataset with more patients and extended follow-up, we further established cancer patient characteristics associated with COVID-19 death. Methods Data on all cancer patients with a positive reverse transcription-polymerase chain reaction swab for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at Guy’s Cancer Centre and King’s College Hospital between 29 February and 31 July 2020 was used. Cox proportional hazards regression was performed to identify which factors were associated with COVID-19 mortality. Results Three hundred and six SARS-CoV-2-positive cancer patients were included. Seventy-one had mild/moderate and 29% had severe COVID-19. Seventy-two patients died of COVID-19 (24%), of whom 35 died 2–5 years [2.81 (1.41–5.59)] or ≥5 years were associated with an increased mortality. Age >60 years and raised C-reactive protein (CRP) were also associated with COVID-19 death. Haematological cancer, a longer-established cancer diagnosis, dyspnoea at diagnosis and raised CRP were indicative of early COVID-19-related death in cancer patients ( Conclusions Findings further substantiate evidence for increased risk of COVID-19 mortality for male and Asian cancer patients, and those with haematological malignancies or a cancer diagnosis >2 years. These factors should be accounted for when making clinical decisions for cancer patients.

Alfonso Papa,1 Maria Teresa Di Dato,1 Giuliano Lo Bianco,1– 3 Giuseppe Gazzerro,1 Anna Maria Salzano,1 Emilio Di Costanzo,1 Dario Tammaro,1 Michael E Schatman,4,5 Giustino Varrassi6 1Pain Department AO “Ospedali dei Colli”, Monaldi Hospital, Naples, Italy; 2Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Catania, Italy; 3Anesthesiology and Pain Department, Fondazione Istituto G. Giglio, Cefalù, Italy; 4Department of Anesthesiology, Perioperative Care, and Pain Medicine, NYU School of Medicine, New York, NY, USA; 5School of Social Work, North Carolina State University, Raleigh, NC, USA; 6Paolo Procacci Foundation, Rome, ItalyCorrespondence: Giuliano Lo Bianco Tel +393289682219Email giulianolobianco@gmail.comObjective: Osteoarthritis (OA) is the most common cause of chronic knee pain, often a debilitating condition that can cause a significant reduction in functional capacity. Radiofrequency is a form of neuromodulation that modulates pain signal transmission and has become progressively more common as a treatment for knee pain. This retrospective study aims to evaluate the efficacy of intraarticular radiofrequency in patients with chronic knee OA pain.Materials and Methods: In this retrospective study, we included 129 patients undergoing intraarticular pulsed radiofrequency using the Poisson curve for energy distribution (Sluijter-Teixeira Poisson radiofrequency) (STP) from March 2018 to November 2019. Knee osteoarthritis severity was assessed prior to the procedure using the Lequesne Index, classifying patients into six groups based on level of severity. Pain intensity was assessed through a 10-cm visual analog scale (VAS), and level of patient satisfaction was assessed through a questionnaire.Results: In the sample, pain reduction as measured by VAS compared to baseline prior to the procedure was statistically significant immediately following the procedure, at 30 days and at 90 days (p< 0.001); this difference was less significant at 180 days (p< 0.005). Efficacy in patients with moderate to severe disability was considerably greater than in patients with very severe to extremely severe disability. 57.36% reported that they were very satisfied, 29.46% satisfied, 9.3% neither satisfied nor dissatisfied, 2.33% dissatisfied, and 1.55% very dissatisfied.Conclusion: Our results suggest that STP radiofrequency may be a safe and effective procedure for knee OA, able to signi&filig;cantly reduce VAS scores at 1 month and 3 months compared to baseline. Based on our results, a key factor to consider when treating knee OA with STP radiofrequency is that it is more effective among patients with a lower level of disability. Due to the retrospective observational study design, prospective longitudinal investigation is required to further support the recommendation of STP radiofrequency for knee OA.Keywords: pulsed radiofrequency treatment, knee joint, osteoarthritis, knee, chronic pain

La hiperglucemia con o sin diabetes en pacientes hospitalizados con COVID-19 se asocia con complicaciones. No existe información del problema en nuestro entorno. El objetivo del estudio fue comparar las características y curso clínico intrahospitalario de los pacientes con diagnóstico de COVID-19 que presentaron o no hiperglucemia durante su hospitalización. Estudio retrospectivo, observacional, de revisión de historias clínicas de pacientes hospitalizados con COVID-19. Se usó el formulario desarrollado por ISARIC y OMS para recopilar datos. Siguiendo los objetivos glucémicos estándar en pacientes hospitalizados, se definió como hiperglucemia, al valor en ayunas igual o mayor de 140 mg/ dL. Se incluyeron 148 pacientes, 97 (65,5%) hombres y 51 mujeres (34,5%), con edad promedio de 64,1±16,1 años, de los cuales 42 (28,4%), refirieron antecedente de diabetes, 60 (40,5%) presentaron hiperglucemia intrahospitalaria y 32 (53,3%) de estos casos no reportaron diabetes previa. Los pacientes con hiperglucemia tenían mayor edad, recibieron más corticoides sistémicos (96,6 vs 82,6%; p=0,01), antibióticos (68,3 vs 44,3%; p=0,01), presentaron mayor alteración en la oxigenación de ingreso (SpO2 88,1±11,7% vs 92,8±5,5%, p=0,02; PaO2/FiO2, 194,4±119,7 vs 270,9±118,3, p

Assisted reproductive techniques are becoming more and more essential for human life in the Society. Worldwide more than 5 million babies were born out of this technology after the birth of first baby Louis Brown and second Durga (India) in 1978. It is a boon for the couple in despair to have a child especially when it is provided by Govt Institutions for the less affordable people of the Society. It is essential to share provider’s experiences and expectations of the public in a fast growing biomedical field like ART. The techniques of IVF and ICSI have undergone a sea change since the initial technique of natural cycles to ovarian hyper stimulation and stem cell research. A 29 year old lady, Type I Diabetic with hirsutism, PCOS, failed IUI underwent ICSI following ovarian stimulation employing antagonist protocol after 8 years of married life. The husband is also diabetic for 13 years and suffered from post-polio residual paralysis and had asthenospermia. Frozen Embryo transfer of cleavage stage embryos was done on 31.7.2019 after endometrial preparation employing HRT. Her β HCG was HCG 387 on 14.8.2019 and intrauterine pregnancy was confirmed by transvaginal scan. Pregnancy and Diabetes were managed with progesterone support and Insulin therapy respectively. An alive male baby was delivered by emergency Caesarean section on 28.3.2020 at 12.34 PM for breech presentation in labour during lockdown for COVID 19. Both mother and baby were discharged home in healthy condition and the baby is one year old at the time of writing this report.