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Background: Intraplaque hemorrhage (IPH) is associated with plaque progression and ischemic events, and plaque lipid content (% lipid core) predicts the residual atherosclerotic cardiovascular disease risk. This study examined the impact of IPH on lipid content change in the setting of intensive lipid-lowering therapy. Methods: In total, 214 AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low High-Density Lipoprotein/High Triglycerides: Impact on Global Health Outcomes) participants with clinically established ASCVD and low high-density lipoprotein cholesterol received cartoid MRI at baseline and 2 years to assess changes in carotid morphology and composition. Patients were randomized to extended-release niacin or placebo, and all received simvastatin with optional ezetimibe as necessary to lower low-density lipoprotein cholesterol to 40 to 80 mg/dL. Changes in lipid content and carotid morphology were tested using the Wilcoxon signed-rank test. Differences between subjects with and without IPH and between subjects assigned extended-release niacin or placebo were tested using the Wilcoxon rank-sum test. Linear regression was used to test the association of IPH and lipid content changes after adjusting for clinical risk factors. Results: Among 156 patients (61±9 years; 81% men) with complete MRI, prior statin use: 5 years, 37%. Triglycerides and ApoB decreased significantly, whereas high-density lipoprotein cholesterol and ApoA1 increased significantly over time. Plaque lipid content was significantly reduced (−0.5±2.4 %/year, P = 0.017) without a significant difference between the 2 treatment groups. However, the lipid content increased in plaques with IPH but regressed in plaques without IPH (1.2±2.5 %/year versus −1.0±2.2, P = 0.006). Additionally, IPH was associated with a decrease in lumen area (−0.4±0.9 mm2/year versus 0.3±1.4, P = 0.033). IPH remained significantly associated with increase in lipid content in multivariable analysis (54.4%, 95% CI: 26.8, 88.0, P < 0.001). Conclusions: Carotid plaques under continued intensive lipid-lowering therapy moved toward stabilization. However, plaques with IPH showed greater increases in lipid content and greater decreases in lumen area than plaques without IPH. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01178320.

Background It is recommended to have 6 bicortical screws for plate fixation of long bone fractures; however, many metacarpal fractures do not allow 6 screws due to size limitations and proximity of crucial anatomical structures. The purpose of this biomechanical study was to determine whether the mechanical properties of a 4-screw nonlocking construct are noninferior to those of a 6-screw nonlocking construct. Methods Metacarpal sawbones were used to simulate a midshaft, transverse fracture. Nonlocking bicortical screws were placed in the 6-hole plate, and the metacarpals were randomly assigned to 2 equal study groups: (1) 4 screws, 2 on either side of the fracture (4S); and (2) 6 screws, 3 on either side of the fracture (6S). The metacarpals were tested in a cyclic loading mode and load to failure in a cantilever bending mode. Results Maximum deflection was significantly higher for 4S compared with 6S. Cyclic root mean square (RMS) was also significantly greater for 4S at 70 and 100 N. There were no statistically significant differences observed between the 2 constructs for maximum bending load, bending stiffness, and cyclic RMS at 40 N. The maximum bending load in 4S and 6S was 245.6 ± 37.9 N and 230.8 ± 41.9 N, respectively; 4S was noninferior and not superior to 6S. Noninferiority testing was inconclusive for bending stiffness. Conclusions A 4-screw bicortical nonlocking construct is noninferior to a 6-screw bicortical nonlocking construct for fixation of metacarpal fractures, which may be advantageous to minimize disruption of soft tissues while maintaining sufficient construct stability.

Objective: Silver–Russell syndrome (SRS) causes short stature. Growth hormone (GH) treatment aims to increase adult height. However, data are limited on the long-term outcomes of GH in patients with molecularly confirmed SRS. This study evaluated height, body mass index (BMI) and GH treatment in molecularly confirmed SRS. Design: An observational study with retrospective data collection. Patients: Individuals with molecularly confirmed SRS aged ≥13 years. Measurements: Data were collected on height, height gain (change in height standard deviation score [SDS] from childhood to final or near-final height), BMI and gain in BMI (from childhood to adulthood) and previous GH treatment. Results: Seventy-one individuals (40 female) were included. The median age was 22.0 years (range 13.2–69.7). The molecular diagnoses: H19/IGF2:IG-DMR LOM in 80.3% (57/71); upd(7)mat in 16.9% (12/71) and IGF2 mutation in 2.8% (2/71). GH treatment occurred in 77.5% (55/71). Total height gain was greater in GH-treated individuals (median 1.53 SDS vs. 0.53 SDS, p =.007), who were shorter at treatment initiation (−3.46 SDS vs. −2.91 SDS, p =.04) but reached comparable heights to GH-untreated individuals (−2.22 SDS vs. −2.74 SDS, p =.7). In GH-treated individuals, BMI SDS was lower at the most recent assessment (median −1.10 vs. 1.66, p =.002) with lower BMI gain (2.01 vs. 3.58, p =.006) despite similar early BMI SDS to GH-untreated individuals (median −2.65 vs. −2.78, p =.3). Conclusions: These results support the use of GH in SRS for increasing height SDS. GH treatment was associated with lower adult BMI which may reflect improved metabolic health even following discontinuation of therapy.

Intratumoral delivery of plasmid IL12 via electroporation (IT-tavo-EP) induces localized expression of IL12 leading to regression of treated and distant tumors with durable responses and minimal toxicity. A key driver in amplifying this local therapy into a systemic response is the magnitude and composition of immune infiltrate in the treated tumor. While intratumoral IL12 typically increases the density of CD3+ tumor-infiltrating lymphocytes (TIL), this infiltrate is composed of a broad range of T-cell subsets, including activated tumor-specific T cells, less functional bystander T cells, as well as suppressive T regulatory cells. To encourage a more favorable on-treatment tumor microenvironment (TME), we explored combining this IL12 therapy with an intratumoral polyclonal T-cell stimulator membrane-anchored anti-CD3 to productively engage a diverse subset of lymphocytes including the nonreactive and suppressive T cells. This study highlighted that combined intratumoral electroporation of IL12 and membrane-anchored anti-CD3 plasmids can enhance cytokine production, T-cell cytotoxicity, and proliferation while limiting the suppressive capacity within the TME. These collective antitumor effects not only improve regression of treated tumors but drive systemic immunity with control of nontreated contralateral tumors in vivo. Moreover, combination of IL12 and anti-CD3 restored the function of TIL isolated from a patient with melanoma actively progressing on programmed cell death protein 1 (PD-1) checkpoint inhibitor therapy.Implications:This DNA-encodable polyclonal T-cell stimulator (membrane-anchored anti-CD3 plasmid) may represent a key addition to intratumoral IL12 therapies in the clinic.

We investigated the association of nutritional risk and inflammatory marker level with length of stay (LOS) in children and adolescents hospitalized for COVID-19 infection in two pediatric teaching hospitals in a developing country.This was a cross-sectional analytical retrospective study performed in two pediatric hospitals. We included the data from all children and adolescents who were hospitalized with a SARS-CoV-2 infection between March and December 2020. Demographic, anthropometric, clinical, and laboratory data were extracted from electronic medical records. Nutritional risk was assessed according to the STRONGkids tool within 24 hours of admission and was categorized into two levels: ≥4 (high risk) and4 (moderate or low risk). Means or medians were compared between nutritional risk groups using the t test and Mann-Whitney U test, respectively. The association of nutritional risk and inflammatory markers with LOS was estimated using the Kaplan-Meier method and log-rank test. Cox proportional-hazard and linear regression models were performed, and adjusted for sex, age, and respiratory symptoms.From a total of 73 patients, 20 (27.4%) had a STRONGkids score ≥4 at admission, which was associated with a longer LOS even after adjusting (β = 12.30; 1.74-22.9 95% CI; P = 0.023). The same association was observed between LOS and all laboratory markers except for D-dimer.Among children and adolescents with COVID-19, a STRONGkids score ≥4 at admission, lower values of albumin, lymphocytes, and hemoglobin, and higher CRP values were associated with longer LOS.

To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody.YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593).3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]).Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema.F Hoffmann-La Roche.

Leukemia is a rare disease associated with a high mortality rate. The presence of unilateral or bilateral serous retinal detachment (SRD) as a sign of choroidal infiltration can be one of the manifestations of acute leukemia, both as a primary sign or in a relapse. We consolidated the literature on SRD as a sign of leukemic choroidopathy regarding its epidemiology, clinical manifestations, and main imaging diagnostic tools. Well-documented cases regarding acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), relapsed ALL and relapsed AML published until September, 2020, in peer reviewed journals were included. The literature shows an interesting range of choroidal infiltration cases assessed by modern imaging techniques, such as optical coherence tomography (OCT) with and without enhanced depth imaging (EDI) and fluorescein angiography (FA). These tools allow choroidal assessment and better understanding and characterization of this rare condition. Complete ophthalmological workup should be performed in these patients using both FA and EDI-OCT to assess the choroidal anatomy and integrity. An increase in choroidal thickness measured with EDI-OCT can reveal active disease and potentially diagnose a leukemic relapse promptly.

Background Primary Synovial Chondromatosis (PSC) is a rare benign tumor of the synovial membrane in which cartilage metaplasia produces calcific loose bodies within the articular space. Only a few cases are reported in the pediatric population and its etiology remains unknown. This condition typically affects large weight-bearing joints with pain, swelling and decrease range of motion. Due to its slow progressions, delayed diagnosis is frequent and differential diagnosis should consider other chronic arthritis and malignancies. While arthroscopic removal of loose bodies is the current treatment up to now, the association of partial or complete synovectomy is debated. Case presentation We report about a 14-year-old girl with a long-lasting right shoulder pain, especially during movements or exercise, localized tenderness and hypotonia of the glenohumeral joint. No previous trauma was mentioned. Blood exams, Mantoux test and plain radiography of the right shoulder were unremarkable. Ultrasound imaging revealed echogenic and calcified bodies stretching the glenohumeral joint and dislocating the long head of biceps tendon. Magnetic resonance showed a “rice-grain” pattern of the right shoulder. From an arthroscopic surgery, multiple loose white bodies were removed within the synovial membrane, and synovial chondromatosis was confirmed by histological analysis. At one month follow up visit, the patient completely recovered without pain. Conclusion Synovial chondromatosis is a very uncommon cause of mono articular pain in children, especially when it affects shoulder. Pediatricians should keep in mind this condition to avoid delayed diagnosis and treatment, even in consideration of the low risk of malignant transformation. Through this case, we would highlight common diagnostic pitfalls and treatment of synovial chondromatosis.

Proteolytic enzymes are biological catalysts that can compose cosmetic formulations: These enzymes are capable of mimicking the desquamation process of the skin, acting as exfoliants. Although enzymatic exfoliation is not new and commercial products were easily found, there is a lack of scientific literature about this topic.A search was carried out until 2021 in different scientific databases (Web of Science, Scopus, Scielo, PubMed, etc.). In vitro and in vivo studies that evaluated the application of enzymes aiming to exfoliate the skin or with a similar cosmetic or dermatological application were selected.Only 11 articles were found, and, among them, few studies applied enzymes as exfoliants in clinical trials. Nevertheless, the results demonstrate that the enzymes can exfoliate the skin and improve some desired characteristics of the organ. Papain, bromelain, keratinases, and microbial proteases are some enzymes already applied as exfoliants. The study of pH, temperature, and stabilization of the enzymes in cosmetic formulations were also demonstrated to be important aspects to be evaluated, principally in preventing loss of enzyme activity and possible allergens/irritations on the skin.This literature review showed the main aspects that should be evaluated before considering producing or applying proteolytic enzymes in exfoliation products/procedures. The use of enzymatic exfoliation has potential in the cosmetic industry. Hence, further robust in vivo studies are needed before the enzymatic exfoliation can be recommended with safety as a treatment modality in the current conditions.

High-intensity interval training (HIIT) is an exercise modality acknowledged to maintain physical fitness with more engagement in an active lifestyle compared with other traditional exercise models. Nevertheless, its effects on cardiac control and physical performance in an online-guided setting are not yet clarified. The present work assessed physical fitness and heart rate variability (HRV) before and after an online, home-based HIIT program in college-age students while pandemic lockdowns were in effect. Twenty university students (age: 21.9 ± 2.4 years.) that were solely enrolled in online classes were distributed into three groups: control—CON-(n = 6), 14 min of HIIT—HIIT-14-(n = 8), and 21 min of HIIT—HIIT-21-(n = 6). A maximal push-up test was employed to assess muscular endurance and performance, and resting HRV signals were collected with wireless heart rate monitors and were processed in Kubios HRV Std. (Kubios Oy, Finland). There was an increase in total push-up capacity compared to CON (p < 0.05 HIIT-21 vs. CON; p < 0.001 HIIT-14 vs. CON) after 8 weeks. A significant interaction was observed in high-frequency and low-frequency spectra ratios after the HIIT-21 intervention (p < 0.05). The current work demonstrated that either short- or mid-volume online, whole-body HIIT improves muscle strength, whereas mid-volume HIIT (HIIT-21) was the only intervention that developed a sympathovagal adaptation. This study showed promising results on muscular endurance and cardiac autonomic modulation through whole-body HIIT practice at home.

Background: From February 21, the day of hospitalisation in ICU of the first diagnosed case of Covid-19, the social situation and the hospitals’ organisation throughout Italy dramatically changed. Methods: The CIO (Club Italiano dell’Osteosintesi) is an Italian society devoted to the study of traumatology that counts members spread in public and private hospitals throughout the country. Fifteen members of the CIO, Chairmen of 15 Orthopaedic and Trauma Units of level 1 or 2 trauma centres in Italy, have been involved in the study. They were asked to record data about surgical, outpatients clinics and ER activity from the 23rd of February to the 4th of April 2020. The data collected were compared with the data of the same timeframe of the previous year (2019). Results: Comparing with last year, overall outpatient activity reduced up to 75%, overall Emergency Room (ER) trauma consultations up to 71%, elective surgical activity reduced up to 100% within two weeks and trauma surgery excluding femoral neck fractures up to 50%. The surgical treatment of femoral neck fractures showed a stable reduction from 15 to 20% without a significant variation during the timeframe. Conclusions: Covid-19 outbreak showed a tremendous impact on all orthopaedic trauma activities throughout the country except for the surgical treatment of femoral neck fractures, which, although reduced, did not change in percentage within the analysed timeframe.

Background and aim of the work: Understanding the fracture morphology and its relation to the expected outcome and risk of complications is fundamental for proximal humerus fractures (PHFs) management. Most Neer 3- and 4-part fractures may deserve surgical treatment. Unfortunately, plain x-rays may not be able to differentiate between a 3- or 4-part fractures unless an axillary or analogue projection is carried out. Aim of the present study is to evaluate whether a high valgus head-shaft angle degree is predictive of a Neer 4-part rather than a 3-part fracture. Methods: The study included 120 3-(75 cases) and 4-(45 cases) part PHFs (valgus displaced in 98 cases), M:F ratio = 1:2.6, mean age 65.7 years, classified on CT scan images. The humeral head shaft angle was calculated on AP x-rays and statistically correlated with 3 and 4-part fractures to identify values predictive of 4-part fracture. Results: Valgus head/shaft angle was significantly higher in 4-part fractures, especially in the valgus displaced group (p < 0.001). A cutoff value of 168.5° was identified as predictive of a 4-part fracture with a sensibility of 74% and specificity of 78%. Increasing by 1 degree the humeral head-shaft angle, the chance to have a 4-part fracture increases of 3% in the whole population and of 11% in the valgus sub-group. Conclusion: The severity of PHF can be predicted analysing valgus head shaft angle on AP x-rays with a sensibility of 74% and specificity of 78% in identifying a 4-part fracture with a cutoff value of 168.5°.

Distal femur fractures account for 4-6% of osteoporosis related fractures of the femur in the elderly population. They represent a relevant cause of morbidity and mortality in the geriatric population with a reported 1-year mortality reaching 30%. Non-displaced fractures or even displaced fractures in patients with high operative risk can be treated conservatively. However, operative treatment is the most widely accepted management option for displaced fractures. The advantage resides in early mobilization and weight-bearing, reducing risks related with a prolonged immobilization when compared with conservative treatment. On the other hand, the intrinsic difficulty of fixing an osteoporotic bone is a major concern. The presence of osteosynthesis devices or prosthetic implants in the femur can make the surgical treatment more challenging, sometimes limiting therapeutic options. Aim of the present paper is to review the most recent literature about osteoporotic distal femur fractures in the elderly, including periprosthetic and other hardware related fractures, to highlight current evidence on management options and related results as a guide for the daily clinical practice. (www.actabiomedica.it).

Background and aim of the work Revision Arthroplasty (RA) is considered the treatment of choice for periprosthetic femur fractures (PFF) presenting with a loose stem. In the elderly RA may be associated with high post-operative mortality and complications. The aim of this study is to compare mortality and functional outcomes of open reduction internal fixation (ORIF) and RA for B2-B3 PFF in the elderly. Methods The study population included 29 patients (>65 years) surgically treated for B2-B3 PFF at the Orthopedic and Traumatology Unit of Cattinara University Hospital in Trieste (Italy) between January 2015 and December 2019. 16 patients were treated with ORIF and 13 with RA. Mortality and functional outcomes were analyzed. Results In-hospital (6,25% vs 7,69%) and 3 months (6,25 vs 15,38%) mortality was higher in the RA group. Mortality rates were particularly high in the > 85-year-old patients within four months from RA treatment. One year (38,46% and 16,67%) and overall mortality (69,22% and 25%) was higher after ORIF. Average time to weight-bearing and ambulation was 2.6 and 5.25 months for ORIF patients and 1.3 and 2.4 months for RA. A correlation was found between delayed weight-bearing and overall mortality. Conclusions Age is a risk factor for short term mortality following RA. Patients >85 years of age could benefit from a less invasive procedure such as ORIF. Long term outcomes are generally better for patients who undergo RA but further studies are necessary to evaluate the risk-benefit ratio of RA treatment compared to ORIF in elderly patients.

Background To review the current clinical evidence on advantages and risks of early weight bearing (EWB) after internal fixation for tibial plateau fracture. Methods Data source: PubMed and Google Scholar from inception of database to 20 August 2021, using PRISMA guidelines. The included studies were randomized controlled trials, prospective and retrospective observational studies, case reports. Data extraction was performed independently by 2 reviewers. Collected data were compared to verify agreement. Statistical analysis was not performed in this study. Results The literature search produced 174 papers from PubMed and 186 from Google Scholar, with a total amount of 360 papers. The two reviewers excluded 301 papers by title or duplicates. Of the 59 remaining, 33 were excluded after reading the abstract, and 17 by reading the full text. Thus, 9 papers were finally included in the review. Conclusions EWB can be considered safe and effective in selected cases after internal fixation for tibial plateau fractures. Level of evidence Therapeutic Level III.

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The study of bone morphology is of great importance as bone morphology is influenced by factors such as age and underlying comorbidities and is associated with bone mechanical properties and fracture risk. Standard diagnostic techniques used in bone disease, such as Dual-Energy X-ray absorptiometry and ultrasonography do not provide qualitative and quantitative morphological information. In recent years, techniques such as High Resolution Computed Tomography (HR-CT), micro- CT, Magnetic Resonance Imaging (MRI), and Low Field Nuclear Magnetic Resonance (LF-NMR) have been developed for the study of bone structure and porosity. Data obtained from these techniques have been used to construct models to predict bone mechanical properties thanks to finite element analysis. Cortical porosity has been extensively studied and successfully correlated with disease progression and mechanical properties. Trabecular porosity and pore size distribution, however, have increasingly been taken into consideration to obtain a comprehensive analysis of bone pathology and mechanic. Therefore, we have decided to evaluate the ability of micro- CT (chosen for its high spatial resolving power) and LF-NMR (chosen to analyze the behavior of water molecules within trabecular bone pores) to characterize the morphology of trabecular bone in osteoporosis. Trabecular bone samples from human femoral heads collected during hip replacement surgery were from osteoporosis (test group) and osteoarthritis (control group) patients. Our data show that both micro- CT and LF-NMR can detect qualitative changes in trabecular bone (i.e., transition from plate-like to rod-like morphology). Micro- CT failed to detect significant differences in trabecular bone morphology parameters between osteoporotic and osteoarthritic specimens, with the exception of Trabecular Number and Connectivity Density, which are markers of osteoporosis progression. In contrast, LF-NMR was able to detect significant differences in porosity and pore size of trabecular bone from osteoporotic versus osteoarthritic (control) samples. However, only the combination of these two techniques allowed the detection of structural morphometric changes (increase in the larger pore fraction and enlargement of the larger pores) in the trabecular bone of osteoporotic specimens compared to osteoarthritic ones. In conclusion, the combined use of LF-NMR and micro- CT provides a valuable tool for characterizing the morphology of trabecular bone and may offer the possibility for a new approach to the study and modeling of bone mechanics in the context of aging and disease.

Achilles tendon reconstruction with substance loss and infection in the overlying soft tissues is a challenge. There is no standardized treatment in literature for these cases. We describe a one-stage tendon reconstruction, using flexor hallucis longus (FHL) tendon transfer and an anterolateral thigh flap with vascularized fascia lata in a patient with re-rupture of the Achilles tendon, soft tissue infection and a tendon defect of 10 cm in length. The surgical procedure has had a successful outcome; patient has recovered normal gait, has recovered complete ankle range of motion with only a partial loss in plantar flexion of the big toe, without any loss in strength. No complications have emerged at follow-up. This technique is promising in treating large Achilles tendon defects with overlying soft tissue infection in a one-stage procedure.

Background Intrauterine devices (IUDs) are commonly used as contraceptives worldwide. However, pregnancies in patients carrying this kind of device may occur. IUD removal when the woman wishes to continue their pregnancy may be very challenging. Only 9 manuscripts in literature reported such similar procedure. Case presentation We report the case of an hysteroscopic removal of IUD in a young woman at 6 weeks of gestation. Discussion The case reported highlights safety and efficacy of operative hysteroscopy as a method of IUD removal in early pregnancy, although other different methods have been reported in literature. In our opinion, maintaining a low infusion pressure during the procedure may help avoiding potential gestational sac damage and IUD displacement for better grasping.

Kidney international 102(1), 160-172 (2022). doi:10.1016/j.kint.2022.02.042, Published by Elsevier, New York, NY

Background This study was designed to demonstrate the non-inferiority (NI) in overall survival (OS) of suspension of androgen deprivation therapy (ADT) versus maintenance and intermittent versus continuous docetaxel administration in metastatic castration-resistant prostate cancer (mCRPC) patients. Patients and methods mCRPC patients were randomised to first-line docetaxel with maintenance or suspension of ADT. Patients attaining a prostate-specific antigen (PSA) response after four chemotherapy cycles underwent second randomisation to receive continuous or intermittent docetaxel therapy. Six hundred patients were to be randomised to achieve 80% statistical power to demonstrate an NI hazard ratio (HR) of 1.25 of interruption versus maintenance of ADT. Results The trial was prematurely closed when 198 participants were randomised. OS was similar in patients who continued (N = 96) versus those who interrupted (n = 102) ADT during docetaxel therapy (HR 0.98, 95% confidence interval [CI] 0.72–1.33] and those on a continuous (N = 35) versus an intermittent (N = 42) docetaxel schedule (HR 0.86, 95% CI 0.55–1.43). No difference in radiological progression-free survival, PSA response, or toxicity was observed between the study arms. The actual NI hazard margins of OS in Arms A and B patients were 1.33 and 1.43, respectively. Conclusions This trial enrolled one-third of the planned patients; this main weakness dramatically limits the interpretation of the results. ADT discontinuation and switching to an intermittent schedule did not seem to affect docetaxel efficacy. The absence of testosterone recovery in the majority of patients could have been a contributory factor. In men with mCRPC, ADT discontinuation should only be done with regular biochemical and clinical monitoring, with the option of quickly restarting ADT at disease progression.

The term cardiac mass refers to benign or malignant cardiac tumors and cardiac metastases but also to pseudotumors, which is a heterogeneous group consisting of thrombi, vegetations and normal variant structures. While primitive cardiac tumors are rare, metastases and pseudotumors are relatively common. The non-invasive diagnostic approach has not been well established in the literature yet. The first-line non-invasive approach consists of echocardiography, which provides good diagnostic accuracy for masses like thrombi, vegetations and some tumors (mainly myxoma and fibroelastoma). In contrast, for other masses, it does not provide information about the potential malignancy because of poor tissue characterization. Second-line (cardiac computed tomography and cardiac magnetic resonance) or third-line (positron emission tomography-computed tomography) evaluations have been validated in the diagnostic approach to cardiac masses by many studies. In fact, a comprehensive diagnostic approach may establish the diagnosis of malignancy without histological report, which is pivotal for the subsequent therapeutic strategy.The aim of this narrative review is to describe the commonly available non-invasive diagnostic techniques for cardiac masses, their potential and limitations and to suggest a diagnostic pathway for common practice.

23 Pág. Centro de Investigación en Sanidad Animal (CISA), No vaccines or specific antiviral drugs are authorized against Middle East respiratory syndrome coronavirus (MERS-CoV) despite its high mortality rate and prevalence in dromedary camels. Since 2012, MERS-CoV has been causing sporadic zoonotic infections in humans, which poses a risk of genetic evolution to become a pandemic virus. MERS-CoV genome encodes five accessory proteins, 3, 4a, 4b, 5 and 8b for which limited information is available in the context of infection. This work describes 4b as a virulence factor in vivo, since the deletion mutant of a mouse-adapted MERS-CoV-Δ4b (MERS-CoV-MA-Δ4b) was completely attenuated in a humanized DPP4 knock-in mouse model, resulting in no mortality. Attenuation in the absence of 4b was associated with a significant reduction in lung pathology and chemokine expression levels at 4 and 6 days post-infection, suggesting that 4b contributed to the induction of lung inflammatory pathology. The accumulation of 4b in the nucleus in vivo was not relevant to virulence, since deletion of its nuclear localization signal led to 100% mortality. Interestingly, the presence of 4b protein was found to regulate autophagy in the lungs of mice, leading to upregulation of BECN1, ATG3 and LC3A mRNA. Further analysis in MRC-5 cell line showed that, in the context of infection, MERS-CoV-MA 4b inhibited autophagy, as confirmed by the increase of p62 and the decrease of ULK1 protein levels, either by direct or indirect mechanisms. Together, these results correlated autophagy activation in the absence of 4b with downregulation of a pathogenic inflammatory response, thus contributing to attenuation of MERS-CoV-MA-Δ4b., This work was supported by grants from the Government of Spain (BIO2016-75549-R; PID2019-107001RB-I00 AEI/FEDER, UE; SEV 2017-0712 and PIE_INTRAMURAL_LINEA 1-202020E079), CSIC (PIE_INTRAMURAL -202020E043), the European Zoonotic Anticipation and Preparedness Initiative (ZAPI) (IMI_JU_115760), the European Commission (H2020-SC1-2019, ISOLDA Project No. 848166-2), and the U.S. National Institutes of Health (NIH) (2P01AI060699 to I.S.). J.C. and J.H-T: received fellowships from the Ministry of Science an Innovation of Spain (BIO2013- 42869-R and PID2019-107001RB-I00 AEI/FEDER). M.B-P. received a contract from ISOLDA_848166 H2020-SC1-2019-Two-Stage-RTD.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

This work aims to evaluate the effects of enzyme concentration, pH, temperature and time course degree of hydrolysis (DH) of papain regarding further development of pharmaceutical and cosmetic formulations.The hydrolysis of casein, collagen, keratin and porcine skin at pH and temperature ranges of the human skin was evaluated. Also, low contact times of enzyme-substrate were studied. The incorporation of 3mM of cysteine improved the caseinolytic (PU), collagenolytic (CU) and keratinolytic (KU) activities of papain.In general, the increase from 0.1 to 1.0 or 2.0 mgmLThis preformulation study demonstrated that papain concentration, time of application and pH of the product should be evaluated when developing a product to promote the hydrolysis of the proteins of the skin.Ce travail vise à évaluer les effets de la concentration d’enzyme, du pH, de la température et du degré d’hydrolyse (DH) de la papaïne concernant le développement ultérieur de formulations pharmaceutiques et cosmétiques. MÉTHODES: L'hydrolyse de la caséine, du collagène, de la kératine et de la peau porcine à des plages de pH et de température de la peau humaine a été évaluée. De plus, des faibles temps de contact enzyme-substrat ont été étudiés. L'incorporation de 3mM de cystéine a amélioré les activités caséinolytiques (PU), collagénolytiques (CU) et kératinolytiques (KU) de la papaïne. RÉSULTATS: En général, l'augmentation de 0,1 à 1,0 ou 2,0 mg.mLCette étude de pré-formulation a démontré que la concentration de papaïne, le temps d’application et le pH du produit doivent être évalués lors du développement d'un produit pour favoriser l'hydrolyse des protéines de la peau.

Lower limb amputation affects an estimated 1.71 million people in the US. The lack of sensory feedback and proprioception often causes loss of balance which heightens the risk of falls and injury. In this presented paper, a haptic feedback system named HapticLink was developed based on the weight distribution of the prosthetic foot to increase the individual's balance and the self-attribution of the prosthesis. The repeatability and linearity of four different force sensors were tested. The FlexiForce A201 sensors were identified as the optimal choice for the parameters and scenarios investigated. HapticLink consists of four A201 sensors, a microcontroller, and four Vibration Motors (VM). The developed system can determine and convey weight distribution on a prosthetic foot to the wearer as haptic feedback. Initial tests with Lower-Limb Prosthetic (LLP) users were conducted with quantitative results (Directional, Frequency, and Manually Applied Directional Perception tests avg. 94.44

Background and aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events, but their effects on atherosclerotic plaque remain elusive. Using serial magnetic resonance imaging (MRI), we studied changes in carotid plaque lipid content and neovasculature under PCSK9 inhibition with alirocumab. Methods Among patients with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dl but ineligible for high-dose statin therapy, those with lipid core on carotid MRI were identified to receive alirocumab 150 mg every 2 weeks. Follow-up MRI was performed at 3, 6, and 12 months after treatment. Pre- and post-contrast MRI were acquired to measure percent lipid core volume (% lipid core). Dynamic contrast-enhanced MRI was acquired to measure the extravasation rate of gadolinium contrast (Ktrans), a marker of plaque neovasculature. Results Of 31 patients enrolled, 27 completed the study (mean age: 69 ± 9; male: 67%). From 9.8% at baseline, % lipid core was progressively reduced to 8.4% at 3 months, 7.5% at 6 months, and 7.2% at 12 months (p = 0.014 for trend), which was accompanied by a progressive increase in % fibrous tissue (p = 0.009) but not % calcification (p = 0.35). Ktrans was not reduced until 12 months (from 0.069 ± 0.019 min−1 to 0.058 ± 0.020 min−1; p = 0.029). Lumen and wall areas did not change significantly during the study period. Conclusions Regression in plaque composition and neovasculature were observed under PCSK9 inhibition on carotid MRI, which provides unique insight into the biological process of plaque stabilization with disease-modifying therapies.

To explore feasibility of using the vessel length on time-of-flight (TOF) or simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) MRA as an imaging biomarker for brain blood flow, by using arterial spin labeling (ASL) perfusion imaging and 3D phase contrast (PC) quantitative flow imaging as references.In a population of thirty subjects with carotid atherosclerotic disease, the visible intracranial arteries on TOF and SNAP were semi-automatically traced and the total length of the distal segments was calculated with a dedicated software named iCafe. ASL blood flow was calculated automatically using the recommended hemodynamic model. PC blood flow was obtained by generating cross-sectional arterial images and semi-automatically drawing the lumen contours. Pearson correlation coefficients were used to assess the associations between the different whole-brain or hemispheric blood flow measurements.Under the imaging protocol used in this study, TOF vessel length was larger than SNAP vessel length (P 0.001). Both whole-brain TOF and SNAP vessel length showed a correlation with whole brain ASL and 3D PC blood flow measurements, and the correlation coefficients were higher for SNAP vessel length (TOF vs ASL: R = 0.554, P = 0.002; SNAP vs ASL: R = 0.711, P 0.001; TOF vs 3D PC: R = 0.358, P = 0.052; SNAP vs 3D PC: R = 0.425, P = 0.019). Similar correlation results were observed for the hemispheric measurements. Hemispheric asymmetry index of SNAP vessel length also showed a significant correlation with hemispheric asymmetry index of ASL cerebral blood flow (R = 0.770, P 0.001).The results suggest that length of the visible intracranial arteries on TOF or SNAP MRA can serve as a potential imaging marker for brain blood flow.

Background Prehospital plasma transfusion in trauma reduces mortality. However, the underlying mechanism remains unclear. Reduction in shock severity may play a role. Lactate correlates with physiologic shock severity and mortality after injury. Our objective was to determine if prehospital plasma reduces lactate and if this contributes to the mortality benefit of plasma. Methods Patients in the Prehospital Air Medical Plasma trial in the upper quartile of injury severity (Injury Severity Score, >30) were included to capture severe shock. Trial patients were randomized to prehospital plasma or standard care resuscitation (crystalloid ± packed red blood cells). Regression determined the associations between admission lactate, 30-day mortality, and plasma while adjusting for demographics, prehospital crystalloid, time, mechanism, and injury characteristics. Causal mediation analysis determined what proportion of the effect of plasma on mortality is mediated by lactate reduction. Results A total of 125 patients were included. The plasma group had a lower adjusted admission lactate than standard of care group (coefficient, -1.64; 95% confidence interval [CI], -2.96 to -0.31; p = 0.02). Plasma was associated with lower odds of 30-day mortality (odds ratio [OR], 0.27; 95% CI, 0.08-0.90; p = 0.03). When adding lactate to this model, the effect of plasma on 30-day mortality was no longer significant (OR, 0.36; 95% CI, 0.07-1.88; p = 0.23), while lactate was associated with mortality (OR, 1.74 per 1 mmol/L increase; 95% CI, 1.10-2.73; p = 0.01). Causal mediation demonstrated 35.1% of the total effect of plasma on 30-day mortality was mediated by the reduction in lactate among plasma patients. Conclusion Prehospital plasma is associated with reduced 30-day mortality and lactate in severely injured patients. More than one third of the effect of plasma on mortality is mediated by a reduction in lactate. Thus, reducing the severity of hemorrhagic shock appears to be one mechanism of prehospital plasma benefit. Further study should elucidate other mechanisms and if a dose response exists. Level of evidence Therapeutic, level II.

Mechanical influence on secondary fracture healing remains an incompletely understood phenomenon. This is of special importance in biological osteosynthesis, where stability is sacrificed for the sake of an optimal biological fracture environment. Under condition of relative stability, a wide range of biomechanical conditions can be achieved. Mechanobiology, which studies mechanical influences on biological systems has become a large, interdisciplinary field. The aim of this article is to present a comprehensive synthesis of the literature for the practicing clinician, with insights relevant to their practice of fracture care.The MEDLINE online database (Pubmed) was searched in September 2021 for relevant articles Results: The search provided 816 results, which were scanned by the first author by the title and abstract. With relevance to the research topic, 59 articles were chosen and read in detail. Another 70 articles were added by screening the references of relevant articles. A total of 129 articles were read and analysed Conclusions: Mechanical environment plays a crucial role in the fracture healing process. The definition of an optimal mechanical environment still evades us, due to the complexity of the problem. Computational models could replicate the complex mechanical environment of bone healing in humans but require detailed knowledge of mechano-transduction and material properties of healing tissues. The literature reminds us of the importance of adequate stiffness of constructs used under conditions of relative stability. Hopefully, further research in this field will result in not only empirical but more accurate and evidence-based assessments of osteosynthesis fixations.

Traumatic subcutaneous index finger both extensor tendons ruptures are rare injuries. Aim of the present paper is to review the literature about this uncommon lesion and to describe the case of 56 years old woman injured when her hand became stuck under a weight during a wrist hyperflexion movement. Surgical treatment was undertaken after 7 days. An extensor digiti minimi (EDM) tendon transfer and a Pulvertaft tenodesis on the index EDC to middle EDC using wide awake local anesthesia no tourniquet (WALANT) technique was performed. The advantage is to allow immediate visualization of active motion and confirmation of appropriate soft tissue tensioning. In our patient no complications were observed and an early rehabilitation program was started. The patient recovered full function at 2 months and resumed hear heavy labour working activity at 4 months.

IntroductionSciatic nerve injury is an uncommon but potentially devastating complication in hip and pelvis surgery. Intraoperative nerve monitoring (IONM) was applied since the seventies in neurosurgery and spine surgery. Nowadays, IONM has gained popularity in other surgical specialities including orthopaedic and trauma surgery. Aim of this systematic review is to resume the literature evidences about the effectiveness of intraoperative monitoring of sciatic nerve during pelvic and hip surgery.MethodsTwo reviewers (GC and MD) independently identified studies by a systematic search of PubMed and Google Scholar from inception of database to 10 January 2021. Inclusion criteria were: (a) English written papers, (b) use of any type of intraoperative nerve monitoring during traumatic or elective pelvic and hip surgery, (c) comparison of the outcomes between patients who underwent nerve monitoring and patient who underwent standard procedures, (d) all study types including case reports. The present review was conducted in accordance with the 2009 PRISMA statement.ResultsThe literature search produced 224 papers from PubMed and 594 from Google Scholar, with a total amount of 818 papers. The two reviewer excluded 683 papers by title or duplicates. Of the 135 remaining, 72 were excluded after reading the abstract, and 31 by reading the full text. Thus, 32 papers were finally included in the review.ConclusionsThe use of IONM during hip and pelvis surgery is debated. The review results are insufficient to support the routine use of IONM in hip and pelvis surgery. The different IONM techniques have peculiar advantages and disadvantages and differences in sensitivity and specificity without clear evidence of superiority for any. Results from different studies and different interventions are often in contrast. However, there is general agreement in recognizing a role for IONM to define the critical maneuvers, positions or pathologies that could lead to sciatic nerve intraoperative damage.Level of evidenceLevel 2.

Polymorphisms of genes involved in the metabolism and transport of folate and cobalamin could play relevant roles in pregnancy outcomes. This study assessed the prevalence of genetic polymorphisms of folate and cobalamin metabolism-related genes such as MTHFR, MTR, CUBN, and SLC19A1 in pregnant women of a homogeneous Spanish population according to conception, pregnancy, delivery, and newborns complications. This study was conducted on 149 nulliparous women with singleton pregnancies. Sociodemographic and obstetrics variables were recorded, and all patients were genotyped in the MTHFR, MTR, CUBN, and SLC10A1 polymorphisms. The distribution of genotypes detected in this cohort was similar to the population distribution reported in Europe, highlighting that more than 50% of women were carriers of risk alleles of the studied genes. In women with the MTHFR risk allele, there was a statistically significant higher frequency of assisted fertilisation and a higher frequency of preeclampsia and preterm birth. Moreover, CUBN (rs1801222) polymorphism carriers showed a statistically significantly lower frequency of complications during delivery. In conclusion, the prevalence of genetic variants related to folic acid and vitamin B12 metabolic genes in pregnant women is related to mother and neonatal outcomes. Knowing the prevalence of these polymorphisms may lead to a personalised prescription of vitamin intake.

Carbapenem-resistant (CR)This article reviews the mechanisms ofCefiderocol is active against most known

We devised a sutureless "Slim-Mesh" technique to treat ventral hernias, including large-giant/massive ones, reduce intra- and postoperative complications, and lower operation time.Between September 1, 2009 and October 31, 2020, 43 patients with large (10 - 14.9 cm)-giant (15 - 19.9 cm) and massive (≥ 20 cm) ventral hernia were operated at our Department with the above technique. This was a prospective (79%)-retrospective study.This study comprised 22 males and 21 females. Mean age was 63 years. Large-giant and massive hernias were found intraoperatively in 37 and 6 cases respectively. Mean operation time for all hernias was 116 minutes, 104 for large-giant hernias, and 190 for massive. In 53.4% of cases, hernia-neck operative measurement was larger than preoperative size. In 25.5% of cases, laparoscopy found satellite hernias previously undetected by ultrasound- and/or computed tomography scan. A composite mesh and a noncomposite mesh were used in 95% and 5% of cases respectively. For mesh fixation, titanium tacks and absorbable straps were used in 14% and 86% of cases respectively. Mean length of hospital stay was 2.3 days. Mean follow-up time was 3 years and 4 months. In our study, there were 5 early postoperative complications: 3 seromas, 1 trocar-site hernia, and 1 case of cystitis. We found 2 late small symptomless recurrences (4.6%).The sutureless "Slim-Mesh" technique facilitates intra-abdominal introduction, as well as the handling and fixation of giant and monster (36 × 26 cm) meshes. In our experience, "Slim-Mesh" is safe, simple, and fast, and economical even for large-giant/massive ventral hernia repair.

Intramedullary nailing is considered the gold standard technique for the treatment of femoral shaft fractures. A rare complication of this technique is nail bending after a new trauma. In these cases nail removal might be really challenging. The present paper provides a brief review of surgical techniques purposed in the literature for bent nail removal and describes a clinical case. (www.actabiomedica.it)

International audience; Type 1 conventional dendritic (cDC1) cells are necessary for cross-presentation of many viral and tumor antigens to CD8+ T cells. cDC1 cells can be identified in mice and humans by high expression of DNGR-1 (also known as CLEC9A), a receptor that binds dead-cell debris and facilitates XP of corpse-associated antigens. Here, we show that DNGR-1 is a dedicated XP receptor that signals upon ligand engagement to promote phagosomal rupture. This allows escape of phagosomal contents into the cytosol, where they access the endogenous major histocompatibility complex class I antigen processing pathway. The activity of DNGR-1 maps to its signaling domain, which activates SYK and NADPH oxidase to cause phagosomal damage even when spliced into a heterologous receptor and expressed in heterologous cells. Our data reveal the existence of innate immune receptors that couple ligand binding to endocytic vesicle damage to permit MHC class I antigen presentation of exogenous antigens and to regulate adaptive immunity.

Background Central precocious puberty (CPP) has been associated with loss-of-function mutations in 2 paternally expressed genes (MKRN3 and DLK1). Rare defects in the DLk1 were also associated with poor metabolic phenotype at adulthood. Objective Our aim was to investigate genetic and biochemical aspects of DLK1 in a Spanish cohort of children with CPP without MKRN3 mutations. Patients A large cohort of children with idiopathic CPP (Spanish PUBERE Registry) was studied. Genomic deoxyribonucleic acid was obtained from 444 individuals (168 index cases) with CPP and their close relatives. Automatic sequencing of MKRN3 and DLK1 genes were performed. Results Five rare heterozygous mutations of MKRN3 were initially excluded in girls with familial CPP. A rare allelic deletion (c.401_404 + 8del) in the splice site junction of DLK1 was identified in a Spanish girl with sporadic CPP. Pubertal signs started at 5.7 years. Her metabolic profile was normal. Familial segregation analysis showed that the DLK1 deletion was de novo in the affected child. Serum DLK1 levels were undetectable (A and g.-223 G>A) in 2 girls with CPP. However, both had normal DLK1 serum levels. Conclusion Loss-of-function mutations of DLK1 represent a rare cause of CPP, reinforcing a significant role of this factor in human pubertal timing.

Background Lipodystrophy syndromes are a group of disorders characterized by a loss of adipose tissue once other situations of nutritional deprivation or exacerbated catabolism have been ruled out. With the exception of the HIV-associated lipodystrophy, they have a very low prevalence, which together with their large phenotypic heterogeneity makes their identification difficult, even for endocrinologists and pediatricians. This leads to significant delays in diagnosis or even to misdiagnosis. Our group has developed an algorithm that identifies the more than 40 rare lipodystrophy subtypes described to date. This algorithm has been implemented in a free mobile application, LipoDDx®. Our aim was to establish the effectiveness of LipoDDx®. Forty clinical records of patients with a diagnosis of certainty of most lipodystrophy subtypes were analyzed, including subjects without lipodystrophy. The medical records, blinded for diagnosis, were evaluated by 13 physicians, 1 biochemist and 1 dentist. Each evaluator first gave his/her results based on his/her own criteria. Then, a second diagnosis was given using LipoDDx®. The results were analysed based on a score table according to the complexity of each case and the prevalence of the disease. Results LipoDDx® provides a user-friendly environment, based on usually dichotomous questions or choice of clinical signs from drop-down menus. The final result provided by this app for a particular case can be a low/high probability of suffering a particular lipodystrophy subtype. Without using LipoDDx® the success rate was 17 ± 20%, while with LipoDDx® the success rate was 79 ± 20% (p Conclusions LipoDDx® is a free app that enables the identification of subtypes of rare lipodystrophies, which in this small cohort has around 80% effectiveness, which will be of help to doctors who are not experts in this field. However, it will be necessary to analyze more cases in order to obtain a more accurate efficiency value.

Purpose To develop a fully automated vessel wall (VW) analysis workflow (fully automated and robust analysis technique for popliteal artery evaluation, FRAPPE) on the popliteal artery in standardized knee MR images. Methods Popliteal artery locations were detected from each MR slice by a deep neural network model and connected into a 3D artery centerline. Vessel wall regions around the centerline were then segmented using another neural network model for segmentation in polar coordinate system. Contours from vessel wall segmentations were used for vascular feature calculation, such as mean wall thickness and wall area. A transfer learning and active learning framework was applied in training the localization and segmentation neural network models to maintain accuracy while reducing manual annotations. This new popliteal artery analysis technique (FRAPPE) was validated against manual segmentation qualitatively and quantitatively in a series of 225 cases from the Osteoarthritis Initiative (OAI) dataset. Results FRAPPE demonstrated high accuracy and robustness in locating popliteal arteries, segmenting artery walls, and quantifying arterial features. Qualitative evaluations showed 1.2% of slices had noticeable major errors, including segmenting the wrong target and irregular vessel wall contours. The mean Dice similarity coefficient with manual segmentation was 0.79, which is comparable to inter-rater variations. Repeatability evaluations show most of the vascular features have good to excellent repeatability from repeated scans of same subjects, with intra-class coefficient ranging from 0.80 to 0.98. Conclusion This technique can be used in large population-based studies, such as OAI, to efficiently assess the burden of atherosclerosis from routine MR knee scans.

Background It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up. Methods In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1–10.8)]. Results In this extended analysis, M1, S1 and T1–T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P Conclusion Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.

Objective: to assess the role of autopsy in the diagnosis of missed injuries (MI) and definition of trauma quality program goals. Method: Retrospective analysis of autopsy reports and patient’s charts. Injuries present in the autopsy, but not in the chart, were defined as “missed”. MI were characterized using Goldman’s criteria: Class I, if the diagnosis would have modified the management and outcome; Class II, if it would have modified the management, but not the outcome; Class III, if it would not have modified neither the management nor the outcome. We used Mann-Whitney’s U and Pearson’s chi square for statistical analysis, considering p

This study evaluated the toxicity associated with a short course dose-escalated hypofractionated radiation therapy (HFRT) using image guided RT with or without androgen suppression therapy in patients with prostate cancer.This single-center prospective observational study included 132 patients with prostate cancer from 2016 to 2020. Patients received HFRT using image guided RT (84%) with 3-dimensional (91%) or intensity modulated RT (9%). Total prescribed doses were 66 Gy (63%), 63 Gy (12%), and 60 Gy (24%) in 22, 21, or 20 daily fractions depending on organ-at-risk dose constraints. Acute toxicity was scored using Radiation Therapy Oncology Group criteria and the international prostate symptom index. The expanded prostate cancer index composite questionnaire was used to collect quality of life data (ranging from 0-100).The study population consisted of 111 patients who completed RT during a period of 3 years. The risk groups were as follows: low risk (12%), intermediate (32%), and high (56%). None of the patients had suspicious lymph nodes. Ninety percent received androgen suppression therapy. Maximum acute genitourinary and gastrointestinal toxicity peaked at grade 3 in 4 of 111 evaluated patients (4%) and at grade 2 in 7 of 111 evaluated patients (8%), respectively. The average international prostate symptom score increased from 4.8 at pretreatment to 14.0 during week 4 and normalized (5.7) 3 months after treatment completion.The current HFRT dose-escalation trial has demonstrated the feasibility of administering 66 Gy in 22 fractions with low acute gastrointestinal and genitourinary toxicities. Further follow-up will report late toxicities and outcomes.

Three-dimensional (3D) intracranial vessel wall (IVW) magnetic resonance imaging can reliably image intracranial atherosclerotic disease (ICAD). However, an integrated, streamlined, and optimized workflow for IVW analysis to provide qualitative and quantitative measurements is lacking.To propose and evaluate an image analysis pipeline (MOCHA) that can register multicontrast and multitime point 3D IVW for multiplanar review and quantitative plaque characterization.Retrospective.A total of 11 subjects with ICAD (68 ± 10 years old, 6 males).A 3.0 T, 3D time-of-flight gradient echo sequence and T1- and proton density-weighted fast spin echo sequences.Each participant underwent two IVW sessions within 2 weeks. Scan and rescan IVW images were preprocessed using MOCHA. The presence of atherosclerotic lesions was identified in different intracranial arterial segments by two readers (GC and JS, 12 years of vascular MR imaging experience each) following an established review protocol to reach consensus on each of the reviews. For all locations with identified plaques, plaque length, lumen and vessel wall areas, maximum and mean wall thickness values, normalized wall index and contrast enhancement ratio were measured.Percent agreement and Cohen's κ were used to test scan-rescan reproducibility of detecting plaques using MOCHA. Intraclass correlation coefficient (ICC) and Bland-Altman analysis were used to evaluate scan-rescan reproducibility for plaque morphologic and enhancement measurements.In 150 paired intracranial vessel segments, the overall agreement in plaque detection was 92.7% (κ = 0.822). The ICCs (all ICCs 0.90) and Bland-Altman plots (no bias observed) indicated excellent scan-rescan reproducibility for all morphologic and enhancement measurements.Findings from this study demonstrate that MOCHA provides high scan-rescan reproducibility for identification and quantification of atherosclerosis along multiple intracranial arterial segments and highlight its potential use in characterizing plaque composition and monitoring plaque development.4 TECHNICAL EFFICACY: Stage 2.

In this review, we summarize the main points that were raised and highlighted during the pre-conference meeting to the 17(th) European Cystic Fibrosis Society Basic Science Conference, held from 30 March to 2 April, 2022 in Albufeira, Portugal. Keynote lectures provided an update on the latest information regarding the phenomenon of antimicrobial resistance (AMR) in cystic fibrosis (CF). Traditional themes such as in vitro antibiotic susceptibility testing and its clinical value, AMR evolution in persistent Pseudomonas aeruginosa infection and the impact of biofilm on AMR were discussed. In addition, the report gives an overview on very recent AMR-related topics that include an ecological view of AMR in CF lung, referred to as resistome, and novel anti-infective approaches in preclinical or early clinical research such as antibiofilm drugs and bacteriophages. (c) 2022 The Authors. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

The present study aimed to evaluate surgical site infections' clinical and economic impact after distal pancreatectomy.The study was a prospective, monocentric, observational study, including all adult patients who underwent distal pancreatectomy. According to the American Centers for Disease Control and Prevention definition, the surgical site infection assessment was prospectively performed by trained personnel. The Accordion Severity Grading System was used to evaluate the clinical burden of surgical site infection. The hospitalization's total costs were calculated using the hospital expenditure report, excluding the intraoperative costs.During the study period, 414 distal pancreatectomies were performed. The overall incidence of surgical site infection was 26% (106 patients). Surgical site infections were associated with a higher body mass index (P = .022, odds ratio 1.2), positive preoperative rectal swab for multidrug resistant bacteria (P = .010, odds ratio 4.2), and increased operative time (P = .037, odds ratio 1.1). Using the Accordion Severity Grading System, surgical site infections contributed significantly to the total clinical burden (25.5%) and prolonged hospitalization (P.001). Furthermore, surgical site infection doubled the costs (12.915 vs 6.888 euros, P.001).Surgical site infection has a high clinical burden, negatively impacting the postoperative course. The costs and length of stay proportionally increased with the surgical site infection severity, doubling the hospitalization expenses.