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Objective: To assess the variations of Interleukin-6 (IL-6) in patients with SARS-CoV-2 infection treated with Tocilizumab (TCZ) alone or in association with hemoadsorption (HA). Design: Retrospective. Setting: An Intensive Care Unit (ICU) admitting mechanically ventilated patients with SARS-CoV-2 pneumonia. Patients: Four adult patients. Interventions: We compared the blood values of IL-6, C-reactive protein (CRP) and of other biochemical variables including the PaO2/FiO2 in two patients who received TCZ alone and in other 2 in whom it was associated with the HA (TCZ-HA) due to the presence of impending or established organ failures other than the lung. All variables were measured before, during and after the treatment. Main results: In all patients, the IL-6 increased during the treatment; after its termination, its values sharply decreased only in those treated also with HA; conversely, the CRP decreased in all patients; the PaO2/FiO2 increased in three patients and remained stable in the remaining one. Both the TCZ and the HA were well tolerated; all patients were weaned from the mechanical ventilation and discharged from the hospital. Limitations: Although the limited number of patients does not allow to draw firm conclusions, the increase of the IL-6 of can be ascribed to its displacement from cellular and soluble receptors, whereas its decrease is likely due to the scavenging effect exerted by the HA. Although the association TCZ-HA could be valuable in the treatment of the Cytokine Release Storm (CRS) associated with the SARS-CoV-2, the HA could be more effective as it neutralizes a wider panel of inflammatory mediators.

Biallelic mutations in B3GALT6, coding for a galactosyltransferase involved in the synthesis of glycosaminoglycans (GAGs), have been associated with various clinical conditions, causing spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1 or SEMDJL Beighton type), Al-Gazali syndrome (ALGAZ), and a severe progeroid form of Ehlers-Danlos syndrome (EDSSPD2). In the 2017 Ehlers-Danlos syndrome (EDS) classification, Beta3GalT6-related disorders were grouped in the spondylodysplastic EDSs together with spondylodysplastic EDSs due to B4GALT7 and SLC39A13 mutations. Herein, we describe a patient with a previously unreported homozygous pathogenic B3GALT6 variant resulting in a complex phenotype more severe than spondyloepimetaphyseal dysplasia with joint laxity type 1, and having dural ectasia and aortic dilation as additionally associated features, further broadening the phenotypic spectrum of the Beta3GalT6-related syndromes. We also document the utility of repeating sequencing in patients with uninformative exomes, particularly when performed by using "first generations" enrichment capture methods.

The aim of the study was to evaluate the results of an all arthroscopic technique for the treatment of massive rotator cuff tears using the long head of biceps as a graft to reconstruct the superior capsule and to reinforce the cuff. A retrospective review of a consecutive series of arthroscopic repair of massive rotator cuff tears using the long head of biceps tendon was conducted. Twenty-five patients underwent surgery, and none were lost at follow-up. Minimum follow-up period was more than 12 months. Constant, UCLA and VAS scores as clinical outcome were analyzed. Time for surgical procedures was also registered. Two alternative procedures (transosseous or anchors) were employed to fix laterally the long head of biceps to the greater tuberosity and to reinforce the cuff. This choice was essentially determined by the bone quality of the greater tuberosity. All patients of both groups (Transosseous: 15 and Anchors: 10) showed a significant improvement of clinical and functional scores. Difference of the operative times between two procedures was statistically significant in favor of the anchor approach. No intraoperative complications were recorded. Postoperative shoulder stiffness was found in two male patients. In no case biceps tenodesis was performed: Popeye sign was easily detected in 16 patients but they did not complain any superior arm pain and weakness. This technique represents a valid solution for treatment of massive rotator cuff tears resulting safe, easier and cost saving in comparison with other published techniques.

Objective To develop a longitudinal algorithm combining two biomarkers, CA125 and HE4, for early detection of ovarian cancer in women with BRCA mutations. Methods Women with BRCA mutations and intact ovaries were invited to participate in a novel ovarian cancer early detection prospective study. The Risk of Ovarian Cancer Algorithm (ROCA) identifying significant increases above each woman's baseline in serum CA125 and HE4 was performed every four months; abnormal risks triggered a subsequent ultrasound. The study first used a risk algorithm for only CA125, a second algorithm was developed for HE4 and finally a risk algorithm combining the two biomarkers was implemented. The ROCA strategy was compared to Standard of Care (SOC) surveillance strategy. Results A total of 149 women enrolled in the ROCA arm while 43 women enrolled in the SOC arm. Abnormal scores were found in 24% of ROCA CA125 tests, 16% if ROCA CA125 or the novel ROCA HE4 were used independently and reduced to 8% using the new two-marker ROCA, significantly lower than the 15% of abnormal tests seen in the SOC arm (p = 0.042). The average false positive rate among women without ovarian cancer for two-marker ROCA for referral to ultrasound was 6.6% (specificity 93.4%), and for the two-marker ROCA plus ultrasound for referral to surgical consultation was 1.7% (specificity 98.3%). Conclusion A newly developed two-marker ROCA administered every 4 months had lower call-back rates than SOC surveillance. Having established high specificity, the two-marker ROCA score deserves further evaluation for sensitivity in a larger trial.

Background: Humeral shaft fractures account for 1% to 3% of all fractures and approximately 20% of all fracture involving the humerus. The prevalence of non-union for diaphyseal humeral fractures has been reported as 1% to 10% after non-surgical and 10% to 15% after surgical management. Various devices used in treatment of humeral diaphyseal non-union are limited contact dynamic compression plates, locking compression plate (LCP), wave plates, humerus interlocking nail (IMN), Ilizarov external fixators and bone graft struts. Case Description: A 68-year-old man reported a humeral shaft fracture on the left side, due to a simple fall. It was reduced and fixed by IMN. He underwent clinical and radiological follow up. Three months after the intervention, due to persistent pain and impaired function of the left shoulder, the nail was removed and a cemented endoprosthesis was implanted. 3 years later, unsatisfied with the results, he came to our attention and was diagnosed an atrophic non-union in the site of the previous humeral shaft fracture. Moreover, the exams showed a rotator cuff insufficiency. It was decided to perform a single-stage intervention to achieve two goals: cure the humeral shaft non-union and restore the function of the left shoulder. The cemented endoprosthesis was removed, followed by an extensive curettage of the non-union site. A reverse prosthesis was implanted, with an extra-long stem used to stabilize the non-union site, as it was an IMN. An allograft was harvested from a cadaver femur and fixed with two metal cerclages. The patient underwent clinical and radiological follow-up. Complete healing was achieved 8 months later. Conclusion: Humeral shaft nonunion still represent a pathology that pose a serious problem to the surgeon. A correct management should include an accurate pre-operative planning, to achieve the best result possible for the patient.

Different surgical techniques (open and arthroscopic) have been described for the treatment of post-traumatic recurrent anterior instability. The aim of the surgery is to restore when possible, normal shoulder anatomy by repairing the underlying pathology responsible for the instability. Sometimes other surgical techniques are indicated. The purpose of this retrospective study was to investigate the long-term clinical and radiographic results and complications of the open Latarjet procedure after a minimum follow-up of 24 years.A retrospective study was performed for 67 patients treated with an open Latarjet procedure in a single center. Forty of these 67 patients returned for follow-up evaluation and clinical/radiological examination during the year 2018, having had a minimum of 24-year follow-up. Clinical outcomes were analyzed using two functional scores, in addition to the ROM and strength assessment. Radiographic evaluation included several views (AP views in neutral, internal and external rotation and a comparative Bernageau view) RESULTS: A total of 40 patients underwent an open Latarjet procedure. All the patients were avaible for follow-up at an average of 25.6 years. Clinically, no patient reported any episode of dislocation at the time of follow-up. The mean Rowe score and the Walch-Duplay score were 84.5 (range 45-100) and 83.5 (range 55-100), respectively. Non-union/fibrous union was reported in 12.5% of cases, partial resorption of the graft was found in 7.5% of cases, while total resorption was found in 5% of cases. Osteoarthritis was identified in 52.5% (21) of the patients.This long-term follow-up study demonstrated that the open Latarjet procedure is a safe and reliable technique for recurrent anterior shoulder instability. The Latarjet procedure provides good long-term stability although associated with a slight limitation in external rotation.Level III; retrospective cohort comparison; treatment study.

Objective: To assess the variations of the blood levels of immunoglobulins (Ig) in septic shock patients treated with an Ig preparation enriched in IgM and IgA (eIg).Design: The blood levels of Ig in survivors (S) and non-survivors (NS) of a group of septic shock patients were measured before the initial administration (D0) and 1 (D1), 4 (D4), and 7 (D7) days thereafter. The SAPS II score, the capillary permeability, the primary site of infection, the antibiotic appropriateness, and the outcome at 28 days were also assessed.Results: In the interval D0–D7, the IgM increased significantly only in the S while remained stable in NS; the IgA significantly increased in both groups; the IgG did not vary significantly in both groups. At D4, the capillary permeability significantly decreased in S but not in NS.Conclusions: The kinetics of the different classes of Ig after eIg were different between S and NS. This could be related either to (a) different capillary permeability in the two groups or to (b) higher Ig consumption in NS. Further studies to confirm the benefits of eIg in the treatment of sepsis syndrome and to define the specific target population and the correct eIg dose are warranted.

Objective: Cardiofaciocutaneous syndrome (CFCS) is a rare developmental disorder caused by upregulated signaling through the RAS-mitogen-activated protein kinase (MAPK) pathway, mostly resulting from de novo activating BRAF mutations. Children with CFCS are prone to epilepsy, which is a major life-threatening complication. The aim of our study was to define the natural history of epilepsy in this syndrome and exploring genotype–phenotype correlations. Methods: We performed an observational study, including 34 patients with molecularly confirmed diagnosis (11 males, mean age: 15.8 years). The mean follow-up period was 9.2 years. For all patients, we performed neurological examination, cognitive assessment when possible, neuroimaging, electrophysiological assessment and systematic assessment of epilepsy features. Correlation analyses were performed, taking into account gender, age of seizure onset, EEG features, degree of cognitive deficits, type of mutation, presence of non-epileptic paroxysmal events and neuroimaging features. Results: Epilepsy was documented in 64% of cases, a higher prevalence compared to previous reports. Patients were classified into three groups based on their electroclinical features, long-term outcome and response to therapy. A genotype–phenotype correlation linking the presence/severity of epilepsy to the nature of the structural/functional consequences of mutations was observed, providing a stratification based on genotype to improve the clinical management of these patients.

The thyroid-stimulating hormone receptor (TSHR) has been indicated as a putative domestication gene in chicken. Comparison of WGS identified a variant in residue 558 of the transmembrane domain (TM) of TSHR, where the domestic chicken (GGD) presents an arginine, whereas the red jungle fowl (RJF) shares a conserved glycine with other vertebrates. This variant has been demonstrated to be associated with phenotypes that are important for domestication and related to thyroid regulation, such as less fearful behavior, reduced aggressive behavior and reduced dependence on seasonal reproduction in GGD as compared with RJF. By means of molecular dynamics simulations, we highlighted the structural and dynamic differences of variant Gly558Arg in the TSHR TM domain. Alterations in TM helix flexibility, structure and protein overall motion are described. The so-called 'arginine snorkeling' of residue 568 in GGD is observed and we hypothesize it as the originating force that produces the observed whole-protein perturbation in the helix bundle dynamics, capable of altering the TSHR signal transduction. The results are discussed in the context of their implications for a better understanding of biological mechanisms in chicken under control of the thyroid, such as body metabolism, as well as for their usefulness in biomedical research.

Mary S Anthony,1 Mary Anne Armstrong,2 Darios Getahun,3 Delia Scholes,4 Jennifer Gatz,5 Renate Schulze-Rath,6 Debbie Postlethwaite,2 Maqdooda Merchant,2 Amy L Alabaster,2 Giulia Chillemi,2 Tina Raine-Bennett,2 Fagen Xie,3 Vicki Y Chiu,3 Theresa M Im,3 Harpreet S Takhar,3 Michael Fassett,3 Jane Grafton,4 David Cronkite,4 Laura Ichikawa,4 Susan D Reed,4,7 Siu Lui Hui,5 Mary E Ritchey,1 Catherine W Saltus,8 Elizabeth B Andrews,1 Kenneth J Rothman,8 Alex Asiimwe,6 Richard Lynen,9 Juliane Schoendorf101RTI Health Solutions, Research Triangle Park, NC, USA; 2Kaiser Permanente Northern California, Oakland, CA, USA; 3Kaiser Permanente Southern California, Pasadena, CA, USA; 4Kaiser Permanente Washington, Seattle, WA, USA; 5Regenstrief Institute, Indianapolis, IN, USA; 6Bayer AG, Berlin, Germany; 7University of Washington, Seattle, WA, USA; 8RTI Health Solutions, Waltham, MA, USA; 9Bayer HealthCare, Whippany, NJ, USA; 10Bayer OY, Espoo, FinlandObjective: To validate algorithms identifying uterine perforations and intrauterine device (IUD) expulsions and to ascertain availability of breastfeeding status at the time of IUD insertion.Study design and setting: Four health care systems with electronic health records (EHRs) participated: Kaiser Permanente Northern California (KPNC), Kaiser Permanente Southern California (KPSC), Kaiser Permanente Washington (KPWA), and Regenstrief Institute (RI). The study included women ≤50 years of age with an IUD insertion. Site-specific algorithms using structured and unstructured data were developed and a sample validated by EHR review. Positive predictive values (PPVs) of the algorithms were calculated. Breastfeeding status was assessed in a random sample of 125 women at each research site with IUD placement within 52 weeks postpartum.Results: The study population included 282,028 women with 325,582 IUD insertions. The PPVs for uterine perforation were KPNC 77%, KPSC 81%, KPWA 82%, and RI 47%; PPVs for IUD expulsion were KPNC 77%, KPSC 87%, KPWA 68%, and RI 37%. Across all research sites, breastfeeding status at the time of IUD insertion was determined for 94% of those sampled.Conclusions: Algorithms with a high PPV for uterine perforation and IUD expulsion were developed at 3 of the 4 research sites. Breastfeeding status at the time of IUD insertion could be determined at all research sites. Our findings suggest that a study to evaluate the associations of breastfeeding and postpartum IUD insertions with risk of uterine perforation and IUD expulsion can be successfully conducted retrospectively; however, automated application of algorithms must be supplemented with chart review for some outcomes at one research site due to low PPV.Keywords: electronic health records, intrauterine device, breastfeeding, validation study, algorithm, postpartum

The fracture avulsion of the greater tuberosity (GT) represents 2% of all humerus fractures, but the true incidence is likely to be higher, being challenging the initial diagnosis on radiograph. The fracture avulsion of the GT could have different treatments: nondisplaced or minimally displaced fractures are treated conservatively, whereas for displaced or comminuted fractures surgical treatment is preferred. The most important finding of this study is the employment of an all-arthroscopic transosseous augmented technique for the treatment of a displaced humeral GT fracture avulsion. This technique shows all the advantages of the transosseous fixation and arthroscopic approach., Technique Video Video 1 The video shows a novel transosseous arthroscopic technique for the treatment of fracture avulsion of the greater tuberosity.

Background The advent of Next Generation Sequencing (NGS) technologies and the concomitant reduction in sequencing costs allows unprecedented high throughput profiling of biological systems in a cost-efficient manner. Modern biological experiments are increasingly becoming both data and computationally intensive and the wealth of publicly available biological data is introducing bioinformatics into the “Big Data” era. For these reasons, the effective application of High Performance Computing (HPC) architectures is becoming progressively more recognized also by bioinformaticians. Here we describe HPC resources provisioning pilot programs dedicated to bioinformaticians, run by the Italian Node of ELIXIR (ELIXIR-IT) in collaboration with CINECA, the main Italian supercomputing center. Results Starting from April 2016, CINECA and ELIXIR-IT launched the pilot Call “ELIXIR-IT HPC@CINECA”, offering streamlined access to HPC resources for bioinformatics. Resources are made available either through web front-ends to dedicated workflows developed at CINECA or by providing direct access to the High Performance Computing systems through a standard command-line interface tailored for bioinformatics data analysis. This allows to offer to the biomedical research community a production scale environment, continuously updated with the latest available versions of publicly available reference datasets and bioinformatic tools. Currently, 63 research projects have gained access to the HPC@CINECA program, for a total handout of ~ 8 Millions of CPU/hours and, for data storage, ~ 100 TB of permanent and ~ 300 TB of temporary space. Conclusions Three years after the beginning of the ELIXIR-IT HPC@CINECA program, we can appreciate its impact over the Italian bioinformatics community and draw some considerations. Several Italian researchers who applied to the program have gained access to one of the top-ranking public scientific supercomputing facilities in Europe. Those investigators had the opportunity to sensibly reduce computational turnaround times in their research projects and to process massive amounts of data, pursuing research approaches that would have been otherwise difficult or impossible to undertake. Moreover, by taking advantage of the wealth of documentation and training material provided by CINECA, participants had the opportunity to improve their skills in the usage of HPC systems and be better positioned to apply to similar EU programs of greater scale, such as PRACE. To illustrate the effective usage and impact of the resources awarded by the program - in different research applications - we report five successful use cases, which have already published their findings in peer-reviewed journals.

BACKGROUND Glenohumeral osteoarthritis (OA) is a common cause of pain and disability affecting nearly a third of the world's population over 60 years of age. As in other joints, shoulder arthroplasty appears to be the most effective treatment. The implant design has evolved during time transitioning to shorter humeral stem lengths or even stemless components. AIM To evaluate the medium-term outcome and survival of a cementless humeral head resurfacing (HHR) in a group of patients affected with OA or avascular necrosis. METHODS This is a retrospective study of prospectively collected data using HHR in 23 patients (15 female and 8 male) after a 7.4 year follow-up. The collected data included clinical and radiographical evaluation. The Constant score, the visual analogue scale, and a clinical evaluation of range of motion were registered pre- and postoperatively. Fifteen patients affected with OA (2 cases of mild, 6 moderate, and 7 severe) and 10 with avascular necrosis (stage III according to Cruess classification) were enrolled. X-rays were evaluated to detect loosening signs, degenerative changes, and superior humeral head migration. Magnetic resonance preoperatively was also performed to assess the rotator cuff status. Tendon integrity was mandatory to implant the HHR. RESULTS In total, 19 patients (21 shoulders) completed the follow-up. Data on 4 shoulders, in 4 patients, were lost because of prosthesis failure. The global revision rate was 16%. A statistically significant improvement in the mean Constant score, visual analogue scale, and range of motion have been reported. No signs of loosening were registered, while in 12 cases a glenoid erosion was found. The osteophytes appeared 7 times on the humeral side and 12 on the glenoid. Superior humeral migration was recorded in only 1 case. CONCLUSION HHR remains a reasonable option in patients with an intact rotator cuff for the treatment of OA and avascular necrosis.

Among the issues affecting the aeronautical field, it is worth highlighting the impact that volcanic eruptions have on airport infrastructures. Such events can lead to delays and flights cancellations. In addition, airports may need to be shut down in order to restore the runway conditions with an important financial impact on the airport and airline companies as well as inconveniences for travelers. Moreover, volcanic ashes suspended in air represent a significant hazard for aircraft in flight: they limit the visibility and can seriously affect both mechanical parts and electronic components. The scope of this work is to develop a machine learning-based model able to predict such events in order to optimize the airport management in case of such extreme and uncontrollable phenomenon.

The fracture-avulsion of the greater tuberosity represents the 2% of all humerus fracture, but the true incidence is likely to be higher, being challenging the initial diagnosis on X-ray. The fracture-avulsion of the greater tuberosity could have different treatment: Non-displaced or minimal displaced fractures are treated conservatively, while for the displaced or comminuted ones the surgical treatment is preferred.

Objectiveto assess the variations of the blood levels of immunoglobulins (Ig) in septic shock patients treated with an Ig preparation enriched in IgM and IgA (eIg).DesignThe blood levels of Ig in survivors (S) and non-survivors (NS) of a group of septic shock patients were measured before the initial administration (D0) and one (D1), four (D4) and seven (D7) days thereafter. The SAPS II score, the capillary permeability, the primary site of infection, the antibiotic appropriateness, the microorganisms isolated and the outcome at 28 days were also assessed.ResultsIn the interval D0-D7 the IgM increased significantly only in the S while remained stable in NS; the IgA significantly increased in both groups; the IgG did not vary significantly in both groups. At D7 the capillary permeability significantly decreased in S but not in NS.ConclusionsThe kinetics of the different classes of Ig after eIg were different between S and NS. This could be related either to (a) different capillary permeability in the two groups and/or (b) higher Ig consumption in NS. Further studies to confirm the benefits of eIg in the treatment of sepsis syndrome, to define the specific target population and the correct eIg dose are warranted.

Purpose: To evaluate the short-term outcomes of rotator cuff repair in the presence of a greater tuberosity cyst (GTC) using a transosseous repair technique. Methods: This study included patients who underwent arthroscopic rotator cuff tear repair with a transosseous technique and were evaluated clinically and by postoperative magnetic resonance imaging (MRI) after 1 year. The inclusion criteria were based on the results of preoperative MRI and were as follows: patients identified as having a repairable full-thickness rotator cuff tear associated with the presence of cystic changes at the tendon insertion site of the greater tuberosity, defined as a GTC involving the footprint area of the torn tendon (supraspinatus and/or infraspinatus tendons). Results: We evaluated 25 patients. The mean preoperative and postoperative American Shoulder and Elbow Surgeons scores were 39.48 (P = .530) and 84.64 (P = .035), respectively; Constant shoulder scores, 38.96 (P < .005) and 80.28 (P = .425), respectively; and University of California–Los Angeles shoulder rating scale scores, 10.6 (P = .045) and 29.04 (P = .315), respectively. The GTC mapping system was easily adopted in all the MRI examinations independently from the quality of the images. The GTCs were mostly located in the superficial anterolateral section of the humeral head and in both the posterolateral sections (superficial and deep). Conclusions: Arthroscopic transosseous rotator cuff repair led to significant mid-term improvement and satisfactory subjective outcomes with low complication and failure rates in this study. The GTC mapping system could be useful to evaluate GTCs and to aid surgeons in the choice of the best surgical technique. Level of Evidence: Level IV, therapeutic case series.

Superior capsular reconstruction (SCR) demonstrated its efficacy as a treatment option available in patients affected with irreparable posterosuperior rotator cuff tears without any signs of arthritis. Originally, the fascia lata autograft was fixed medially to the glenoid (with two or more anchors) and laterally to the greater tuberosity (with a compression double-row technique using four anchors or three transosseous tunnels). Additionally, side-to-side sutures were used to anteriorly and posteriorly connect the graft to the native residual rotator cuff tissue. However, the fascia lata as an autograft has a disadvantage related to the donor-site morbidity. To solve this aspect, allografts were employed with initial promising results. Nowadays, SCR is to be considered a technically demanding and expensive procedure, because of the cost of the allograft plus that of all the anchors employed to fix it. The Arthroscopic Biceps Chillemi's technique addresses these concerns in performing SCR and presents numerous advantages being a safe, easier, time and cost-saving way compared to the other published techniques. This technique has only one conditio sine qua non: the presence of the long head of the biceps tendon (LHB), used as an autograft. This condition may be interpreted as a disadvantage of this procedure in the presence of some anatomic variations of the intra-articular portion of the LHB and the very rare absence of the tendon or in case of partial or complete rupture of the LHB tendon associated with a rotator cuff tear.

This article reconstructs the key passages of the theory of theatre elaborated by French philosopher Alain Badiou. A particular attention is dedicated to four texts: Rapsody for the theatre (the heftiest of the eight essays included in the collection), in which it is enunciated the veritative power of the theatre – onto which scene the encounter between the textual eternity and the scenic instant gives life to events of thought; the programmatic essays Ten thesis on the theatre and Antithesis of the theatre, which explicitly renders the terms of the crucial relationship between truth and art. The sheer originality of Badiou’s heterodox re exion on theatre is the result of a distance from the principles of the theatre of direction and from the strongholds of the «postdramatic theatre» (Hans-Thies Lehmann, 1999). On the one hand, there is a rejection of any theory which makes of the theatrical praxis the enactment of ‘external truths’, that the representation was supposed to make visible. On the other hand, the anti-textual and performative position of the experimental avant-gardes is declined: the protagonists of the theatre are the playwright, the director (the two figures properly artistic) and the spectators («the holders of the theatre-idea»). The true theatre is therefore the «theatre of ideas», of which the actors are nothing but the «pure presence», the mediation, the «ethical mean».

Ferric citrate is an approved phosphate binder for use in patients with chronic kidney disease on dialysis. Clinical trials demonstrated that ferric citrate controlled serum phosphorus levels and increased iron stores. The aim of this retrospective chart review was to evaluate real-world bone mineral and anemia parameter data from patients treated with ferric citrate. 92 adult dialysis patients taking ferric citrate (average starting dose of 6 tablets/day) for at least 6 months were included. Bone mineral, anemia, and iron biomarker levels were extracted from patient medical records before and during the first 6 months of ferric citrate treatment; 21 (23%) patients were phosphate binder naive, and 71 (77%) patients had been on other phosphate binders. Before starting ferric citrate, 22% of patients had serum phosphorus ≤ 5.5 mg/dL, increasing to 65% of patients at 6 months of treatment (month 6). Mean (standard error of the mean (SEM)) baseline serum phosphorus was 6.55 ± 0.17 mg/dL decreasing to 5.40 ± 0.17 mg/dL at month 6. Mean (SEM) baseline hemoglobin, ferritin, and transferrin saturation were 10.6 ± 0.2 g/dL, 734 ± 65 ng/mL, and 27.1 ± 1.6%, respectively, and 11.1 ± 0.2 g/dL, 947 ± 66 ng/mL, and 37 ± 1.9%, respectively, at month 6. The serum phosphorus and anemia biomarker levels observed in this retrospective chart review were similar to those seen in clinical trials. .

// Federica Costa 1, * , Denise Toscani 1, * , Antonella Chillemi 2 , Valeria Quarona 2 , Marina Bolzoni 1 , Valentina Marchica 1, 6 , Rosanna Vescovini 3 , Cristina Mancini 4 , Eugenia Martella 4 , Nicoletta Campanini 4 , Chiara Schifano 5 , Sabrina Bonomini 5 , Fabrizio Accardi 1, 5 , Alberto L. Horenstein 2 , Franco Aversa 1, 5 , Fabio Malavasi 2 and Nicola Giuliani 1, 5, 6 1 Department of Medicine and Surgery, University of Parma, Parma, Italy 2 Laboratory of Immunogenetics, Department of Medical Sciences and CeRMS, University of Torino, Torino, Italy 3 Clinical Medicine Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy 4 Pathology, “Azienda Ospedaliero-Universitaria di Parma”, Parma, Italy 5 Hematology and BMT Center, “Azienda Ospedaliero-Universitaria di Parma”, Parma, Italy 6 CoreLab, “Azienda Ospedaliero-Universitaria di Parma”, Parma, Italy * These authors contributed equally to this work Correspondence to: Nicola Giuliani, email: nicola.giuliani@unipr.it Keywords: multiple myeloma, CD38, osteoclast, bone disease, immunotherapy Received: October 27, 2016 Accepted: April 29, 2017 Published: May 16, 2017 ABSTRACT It is known that multiple myeloma (MM) cells express CD38 and that a recently developed human anti-CD38 monoclonal antibody Daratumumab mediates myeloma killing. However, the expression of CD38 and other functionally related ectoenzymes within the MM bone niche and the potential effects of Daratumumab on bone cells are still unknown. This study firstly defines by flow cytometry and immunohistochemistry the expression of CD38 by bone marrow cells in a cohort of patients with MM and indolent monoclonal gammopathies. Results indicate that only plasma cells expressed CD38 at high level within the bone niche. In addition, the flow cytometry analysis shows that CD38 was also expressed by monocytes and early osteoclast progenitors but not by osteoblasts and mature osteoclasts. Indeed, CD38 was lost during in vitro osteoclastogenesis. Consistently, we found that Daratumumab reacted with CD38 expressed on monocytes and its binding inhibited in vitro osteoclastogenesis and bone resorption activity from bone marrow total mononuclear cells of MM patients, targeting early osteoclast progenitors. The inhibitory effect was not observed from purified CD14 + cells, suggesting an indirect inhibitory effect of Daratumumab. Interestingly, all-trans retinoic acid treatment increased the inhibitory effect of Daratumumab on osteoclast formation. These observations provide a rationale for the use of an anti-CD38 antibody-based approach as treatment for multiple myeloma-induced osteoclastogenesis.

We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests and pelvic ultrasounds every 6 months.Women were recruited 6/13/16-9/11/17 from an integrated health care system in California for this non-randomized prospective cohort study. Women were invited to participate in a novel serum biomarker surveillance strategy using ROCA or they could opt to be in the standard of care control arm with ultrasound and CA 125 every 6 months. Outcomes assessed included compliance, self-reported distress using the Impact of Event Scale (IES) and cancer anxiety using the Cancer Worry Scale.There were 159 women in the ROCA arm and 43 in the SOC arm. Overall, compliance was higher in the ROCA arm (83.2%) than in SOC (51.9%), p 0.0001. Based on the IES, ROCA arm women reported less feelings about intrusion and avoidance at 12 months compared to baseline; the difference approached significance for intrusion (7.6% vs 4.1% severe, p = 0.057) and was statistically significant for avoidance (20.8% vs 9.9% severe, p = 0.034).This pilot demonstrated that compliance was high with blood tests performed every four months for ovarian cancer surveillance. Moreover, ROCA women had lower stress scores over time than SOC women. Given the lack of clinical utility and poor compliance shown with traditional ultrasound and CA125 tests, further investigation is warranted of longitudinal biomarker surveillance for early detection of ovarian cancer.

Background: Variable return-to-play (RTP) rates have been reported after surgical repair of superior labral anterior-posterior (SLAP) tears in baseball players. Many studies, however, have not controlled for concomitant shoulder injuries. Purpose/Hypothesis: The purpose of this study was to evaluate rates of RTP and return to previous or higher performance level (RTPP) and long-term outcomes after isolated SLAP tear repair. The hypothesis was that improved outcomes would be identified compared with previous reports. Study Design: Case series; Level of evidence, 4. Methods: The records of 232 players who underwent isolated SLAP tear repair from 2004 to 2014 were reviewed. A total of 98 players who were at least 12 months out from surgery were identified. Through telephone interviews, participants completed the Western Ontario Shoulder Instability Index (WOSI) and Veterans RAND 12-Item Health Survey (VR-12) and answered scripted questions about RTP, RTPP, and current symptoms. Results: Of the 98 players who met the inclusion criteria, 73 (74.5%) participated. The mean age at the time of surgery was 19.8 ± 2.9 years. The mean follow-up time was 86.2 ± 25.1 months overall; it was 84.4 ± 24.4 months for pitchers and 90.3 ± 26.7 months for other position players, (P = .40). There were 10 professional, 36 collegiate, and 27 high school players. Most players perceived successful RTP (83.6%), including 80.0% of pitchers and 91.3% of other position players (P = .23). However, RTPP rates were lower, at 52.3% (n = 26) and 78.3% (n = 18) for pitchers and other position players, respectively (P = .03). Pitchers were younger at the time of surgery (19.3 ± 3.0 vs 20.8 ± 3.0 years, respectively; P = .03) and had greater perceived shoulder and general health impairments compared with other position players (P ≤ .02). Players who perceived successful RTPP had better WOSI of the healthy shoulder and individual physical, sports, lifestyle, and emotion scores compared with players who did not perceive successful RTPP. Conclusion: After the surgical repair of isolated type II or greater SLAP tears, other position players displayed superior RTP (91.3% vs 80.0%, respectively) and RTPP (78.3% vs 52.3%, respectively) rates than pitchers. Long-term follow-up suggests that pitchers may perceive greater long-term impairments than other position players and are less likely to return to their previous or higher performance level.

Background Intrauterine devices are effective and safe, long-acting reversible contraceptives, but the risk of uterine perforation occurs with an estimated incidence of 1 to 2 per 1000 insertions. The European Active Surveillance Study for Intrauterine Devices, a European prospective observational study that enrolled 61,448 participants (2006–2012), found that women breastfeeding at the time of device insertion or with the device inserted at ≤36 weeks after delivery had a higher risk of uterine perforation. The Association of Uterine Perforation and Expulsion of Intrauterine Device (APEX-IUD) study was a Food and Drug Administration–mandated study designed to reflect current United States clinical practice. The aims of the APEX-IUD study were to evaluate the risk of intrauterine device–related uterine perforation and device expulsion among women who were breastfeeding or within 12 months after delivery at insertion. Objective We aimed to describe the APEX-IUD study design, methodology, and analytical plan and present population characteristics, size of risk factor groups, and duration of follow-up. Study Design APEX-IUD study was a retrospective cohort study conducted in 4 organizations with access to electronic health records: Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Washington, and Regenstrief Institute in Indiana. Variables were identified through structured data (eg, diagnostic, procedural, medication codes) and unstructured data (eg, clinical notes) via natural language processing. Outcomes include uterine perforation and device expulsion; potential risk factors were breastfeeding at insertion, postpartum timing of insertion, device type, and menorrhagia diagnosis in the year before insertion. Covariates include demographic characteristics, clinical characteristics, and procedure-related variables, such as difficult insertion. The first potential date of inclusion for eligible women varies by research site (from January 1, 2001 to January 1, 2010). Follow-up begins at insertion and ends at first occurrence of an outcome of interest, a censoring event (device removal or reinsertion, pregnancy, hysterectomy, sterilization, device expiration, death, disenrollment, last clinical encounter), or end of the study period (June 30, 2018). Comparisons of levels of exposure variables were made using Cox regression models with confounding adjusted by propensity score weighting using overlap weights. Results The study population includes 326,658 women with at least 1 device insertion during the study period (Kaiser Permanente Northern California, 161,442; Kaiser Permanente Southern California, 123,214; Kaiser Permanente Washington, 20,526; Regenstrief Institute, 21,476). The median duration of continuous enrollment was 90 (site medians 74–177) months. The mean age was 32 years, and the population was racially and ethnically diverse across the 4 sites. The mean body mass index was 28.5 kg/m2, and of the women included in the study, 10.0% had menorrhagia ≤12 months before insertion, 5.3% had uterine fibroids, and 10% were recent smokers; furthermore, among these women, 79.4% had levonorgestrel-releasing devices, and 19.5% had copper devices. Across sites, 97,824 women had an intrauterine device insertion at ≤52 weeks after delivery, of which 94,817 women (97%) had breastfeeding status at insertion determined; in addition, 228,834 women had intrauterine device insertion at >52 weeks after delivery or no evidence of a delivery in their health record. Conclusion Combining retrospective data from multiple sites allowed for a large and diverse study population. Collaboration with clinicians in the study design and validation of outcomes ensured that the APEX-IUD study results reflect current United States clinical practice. Results from this study will provide valuable information based on real-world evidence about risk factors for intrauterine devices perforation and expulsion for clinicians.

Molecular dynamics (MD) simulation allows one to predict the time evolution of a system of interacting particles. It is widely used in physics, chemistry and biology to address specific questions about the structural properties and dynamical mechanisms of model systems. MD earned a great success in genome research, as it proved to be beneficial in sorting pathogenic from neutral genomic mutations. Considering their computational requirements, simulations are commonly performed on HPC computing devices, which are generally expensive and hard to administer. However, variables like the software tool used for modeling and simulation or the size of the molecule under investigation might make one hardware type or configuration more advantageous than another or even make the commodity hardware definitely suitable for MD studies. This work aims to shed lights on this aspect.

Purpose The aim of the present retrospective study is to describe the results obtained at 2-year follow-up by using a porcine dermis-derived collagen membrane implanted as augmentation to treat large rotator cuff tears. Methods Thirty-five patients in total were included according to the following criteria: large or massive rotator cuff tear, confirmed during surgery, measuring between 3 and 5 cm in width and stage 1 to 2 fatty infiltration documented at magnetic resonance imaging (MRI). Patients underwent arthroscopic repair of the cuff augmented by the implantation of a porcine dermal collagen membrane. Patients were evaluated up to 24 months after surgery by the Constant score and MRI imaging to assess functional outcomes and re-tear rate. The results obtained were compared to those of a matched cohort of 35 patients operated by arthroscopic repair alone by the same surgical team. Results The application of the porcine membrane proved to be safe without scaffold-related adverse events documented. A statistically significant difference in the Constant score in favor of the treatment group was documented at the final evaluation (p = 0.036). Furthermore, a subgroup analysis revealed that patients treated by augmentation and presenting re-tear at MRI showed a significantly higher functional outcome compared with control patients with MRI evidence of re-tear (p = 0.0136). Conclusion Arthroscopic repair augmented by porcine dermal xenograft for the treatment of chronic and retracted rotator cuff tears with low-grade fatty degeneration proved to be safe and also effective, with higher functional score compared with the arthroscopic repair alone. Level of Evidence This is a Level III, retrospective cohort study.

Background The administration of endovenous immunoglobulins in patients with septic shock could be beneficial and preparations enriched with IgA and IgM (ivIgGAM) seem to be more effective than those containing only IgG. In a previous study Berlot et al. demonstrated that early administration of ivIgGAM was associated with lower mortality rate. We studied a larger population of similar patients aiming either to confirm or not this finding considering also the subgroup of patients with septic shock by multidrug-resistant (MDR) pathogens. Methods Adult patients with septic shock in intensive care unit (ICU) treated with ivIgGAM from August 1999 to December 2016 were retrospectively examined. Collected data included the demographic characteristics of the patients, the diagnosis at admission, SOFA, SAPS II and Murray Lung Injury Score (LIS), characteristics of the primary infection, the adequacy of antimicrobial therapy, the delay of administration of ivIgGAM from the ICU admission and the outcome at the ICU discharge. Parametric and nonparametric tests and logistic regression were used for statistic analysis. Results During the study period 107 (30%) of the 355 patients died in ICU. Survivors received the ivIgGAM earlier than nonsurvivors (median delay 12 vs 14 h), had significantly lower SAPS II, SOFA and LIS at admission and a lower rate of MDR- and fungal-related septic shock. The appropriateness of the administration of antibiotics was similar in survivors and nonsurvivors (84 vs 79%, respectively, p: n.s). The delay in the administration of ivIgGAM from the admission was associated with in-ICU mortality (odds ratio per 1-h increase = 1.0055, 95% CI 1.003–1.009, p

A large population of fixed-type agents engage in exclusive pairwise relationships in a decentralized setting. At the onset, agents randomly meet in pairs under private information of individual time-invariant types. They play a voluntary contribution game. At the end of the first period, members of each pair either stay together in the second period, in which case reported information is common knowledge, or quit and meet randomly new partners, under private information of individual types. Thus, either long-term or short-term relationships may arise. We show that there are values of the parameters such that information extracted in the first period has a positive effect on social efficiency. We give an interpretation of our results in terms of advantageous delegation of decisions to uninformed agents. Finally, we consider several extensions of the model in which our results still hold.

The aim of this study is a radiographic evaluation and to determine serologic values of chromium and cobalt in the blood and urine of patients who have been implanted with a Stryker® ABG II Modular Neck and see if there is correlation with the features of prosthesis and patients. The study involves the collection of data from patients operated on for total hip model with the ABG II Modular Neck with a minimum follow-up of 1 year. We evaluated 22 patients who underwent implantation of a hip prosthesis with modular neck in CoCr. Of these, the average Cr in the blood was 0.63 μgL−1 (range 0.1–2.15 μgL−1), the average of Co in the blood was 3.50 μgL−1 (range 0.62–7.78 μgL−1), the average Cr in the urine was 1.24 μgL−1 (range 0.48–2.21 μgL−1), and the average Co in urine was 14.22 μgL−1 (range 3.3–31.2 μgL−1). None of these patients had undergone revision surgery. Our study seems to indicate that the restoration of offset and age are correlated with the release of metal ions, although the correlation is weak and needs better methodological studies and a greater number of patients to confirm this hypothesis. Case series Level of Evidence 4.

In this paper, the two authors introduce their project of translating Carmelo Bene’s oeuvre into English. The essay highlights the relevance of his accomplishments to contemporary debates in aesthetics and stresses the importance of disseminating his multifaceted works in the Anglosphere. After retracing the main stages of Bene’s career in theatre, literature, film, and music, the authors illustrate how Benean production particularly reshapes the concept and practice of Western performance, justifying their decision to begin the translation project with his theatrical works.

Transient infantile hypertriglyceridemia (HTGT1; OMIM #614480) is a rare autosomal recessive disorder, which manifests in early infancy with transient hypertriglyceridemia, hepatomegaly, elevated liver enzymes, persistent fatty liver and hepatic fibrosis. This rare clinical entity is caused by inactivating mutations in the GPD1 gene, which encodes the cytosolic isoform of glycerol-3-phosphate dehydrogenase. Here we report on four patients from three unrelated families of diverse ethnic origins, who presented with hepatomegaly, liver steatosis, hypertriglyceridemia, with or without fasting ketotic hypoglycemia. Whole exome sequencing revealed the affected individuals to harbor deleterious biallelic mutations in the GPD1 gene, including the previously undescribed c.806G > A (p.Arg269Gln) and c.640T > C (p.Cys214Arg) mutations. The clinical features in three of our patients showed several differences compared to the original reports. One subject presented with recurrent episodes of fasting hypoglycemia along with hepatomegaly, hypetriglyceridemia, and elevated liver enzymes; the second showed a severe liver disease, with intrahepatic cholestasis associated with kidney involvement; finally, the third presented persistent hypertriglyceridemia at the age of 30 years. These findings expand the current knowledge of this rare disorder, both with regard to the phenotype and molecular basis. The enlarged phenotypic spectrum of glycerol-3-phosphate dehydrogenase 1 deficiency can mimic other inborn errors of metabolism with liver involvement and should alert clinicians to recognize this entity by considering GPD1 mutations in appropriate clinical settings.

The claustrum is a thin grey matter structure which is involved in a wide brain network. Previous studies suggested a link between claustrum and Parkinson’s Disease (PD), showing how α-synuclein pathology may affect claustral neurons as well as how α-synuclein immunoreactivity may correlate with the onset of cognitive dysfunctions. Our aim is to investigate, via diffusion MRI, claustral structural network changes in drug naive PD patients, with the goal to understand whether such changes may contribute to cognitive decline in PD. 15 drug naive PD patients and 15 age-matched controls were enrolled; MR protocol was performed on a 3T scanner. Whole brain probabilistic tractography was obtained using Constrained Spherical Deconvolution (CSD) diffusion model. Connectivity matrices were estimated based on a robust anatomical parcellation of structural T1w images. In PD group, impaired subnetworks were correlated with psychological examinations. We found decreased claustral connectivity in PD patients compared to controls, especially with areas mainly involved in visuomotor and attentional systems. Moreover, we found a positive correlation between MoCA and density of pathways connecting ipsilaterally claustrum to left (r = 0.578, p = 0.021) and right (r = 0.640, p = 0.020) Pars Orbitalis. Our results support the hypothesis of claustral involvement in cognitive decline in drug naive PD patients.

Several techniques and protocols of non-invasive transcranial brain stimulation (NIBS), including transcranial magnetic and electrical stimuli, have been developed in the past decades. These techniques can induce long lasting changes in cortical excitability by promoting synaptic plasticity and thus may represent a therapeutic option in neuropsychiatric disorders. On the other hand, despite these techniques have become popular, the fragility and variability of the after effects are the major challenges that non-invasive transcranial brain stimulation currentlyfaces. Several factors may account for such a variability such as biological variations, measurement reproducibility, and the neuronal state of the stimulated area. One possible strategy, to reduce this variability is to monitor the neuronal state in real time using EEG and trigger TMS pulses only at pre-defined state. In addition, another strategy under study is to use the spaced application of multiple NIBS protocols within a session to improve the reliability and extend the duration of NIBS effects. Further studies, although time consuming, are required for improving the so far limited effect sizes of NIBS protocols for treatment of neurological or psychiatric disorders.

We study the properties of simple mobile broadband Internet plans characterized by a data cap and an up-front price. Assuming demand uncertainty and a positive correlation between users’ valuations and (expected) demands, we show that a monopolistic provider does always find it convenient to offer one plan with binding cap together with an unlimited one. We characterize all the elements of the profit-maximizing plans, showing that medium users, but not heavy users, will incur the risk of being capped, and that, relative to the benchmark case of unlimited access only, the introduction of a plan with cap leads to a redistribution of surplus from high users to low users. The overall effect on social welfare and users’ surplus is, in general, ambiguous, but is certainly negative if low valuation users have a sufficiently homogeneous demand for Internet traffic.

The paper aims to expound on the philosophical significance of Carmelo Bene’s oeuvre. In the 1970’s and 1980’s, when the international debate in Europe was dominated by French post-structuralism and Derridean deconstructive criticism, Beneian artistic praxis eluded – I contend – the so-called “metaphysics of presence.” First of all, I detect similarities and differences between the theoretical grounding of Bene’s works and Jacques Derrida’s and Giorgio Agamben’s respective philosophical inquiries into the essence of language. Subsequently, I analyze the distinctive stylistic techniques of the television film Amleto da Shakespeare a Laforgue (Hamlet from Shakespeare to Laforgue, 1974). A close attention is paid to the (dis)functions of linguistic and cinematic codes (such as verbal, body, and audiovisual language) and how they interfere with the construction of meaningful, consistent interpretations. Finally, I investigate the phenomenon of ineffability by drawing a parallel between mystical experiences and Beneian performances.

INTRODUCTION: Novel psychoactive substances (NPS) are new psychotropic drugs, not scheduled under the International Conventions on Psychotropic Substances, but which may pose a relevant public health threat. In this study, we investigated knowledge and use of NPS in a sample of Italian youth in urban and rural areas. METHODS: Between December 2012 and October 2013, we administered a questionnaire to a sample of 3011 healthy subjects (44.7% men; 55.3% women), aged between 16 and 24 years and recruited in urban, intermediate and rural areas of Italy. RESULTS: Of the global sample, 53.3% declared to have some knowledge on NPS, with a higher knowledge in urban areas. Mephedrone (26%), desomorphine (22.6%) and methamphetamine (21.7%) were the most commonly known drugs. NPS use was reported by 4.7% of the sample, without significant differences between urban and rural areas; mephedrone (3.3%), synthetic cannabinoids (1.2%) and Salvia divinorum (0.3%) consumption has been identified. NPS use was also predictive of binge-drinking behaviours (χ(2) (4) = 929.58, p DISCUSSION: Urban areas may represent a focal point for preventive strategies, given the presence of higher levels of NPS knowledge. Moreover, the association between binge-drinking habits and NPS use was really strong. This issue should not be underestimated because of its medical, psychopathological and social consequences. Copyright © 2015 John Wiley & Sons, Ltd. Language: en

To evaluate a possible association of shoulder pain with the clinical features and the histopathological changes occurring in the ruptured tendon and subacromial bursa of patients with rotator cuff tear. One hundred and eighty patients were clinically evaluated with the constant score and the visual analogue pain scale. Radiographs and MRI were performed. The chronology of the rupture, the muscle fatty degeneration according to Goutallier’s scale and the tear size were evaluated. For each patient, a biopsy of the supraspinatus tendon and subacromial bursa was performed during arthroscopic rotator cuff tear repair and the specimens were histopathologically analysed. Clinically, the shoulder was more painful in females, in the presence of a chronic cuff lesion and a low Goutallier’s grade (P

The rotator cuff healing process occurs in a special environment because it happens between the tendon and bone. Rotator cuff (RTC) re-tears after surgical repair continue to be a prevalent problem. Despite advances in surgical technique, re-tears occur at rates of 11%–57% (Le et al. 2014). Risk of re-tear has been attributed to many modifiable and non-modifiable factors, including patient age, size and pattern of initial tear, repair technique, and tendon quality (Le et al. 2014; Duquin et al. 2010; Millett et al. 2014; Nho et al. 2009; Chillemi et al. 2011). In a recent study (Chillemi et al. 2011), were detected and listed the most important histopathological findings of ruptured tendons, which consisted mainly in disarray (i.e., loss of structural organization), poor or absent neoangiogenesis, chondral metaplasia, and fibrosis. All these features may give to tendon tissue a low healing capability, so these aspects may therefore explain why the lesions of the rotator cuff are at high risk of re-tear. Taking into considerations these observations, was so introduced a new concept of rotator cuff tendon “non-healing” (i.e., a condition of healing failure) rather than re-tear.

Tear recurrence is considered the main complication of a rotator cuff repair. The best arthroscopic technique has not yet been established. The aim of the present study was to evaluate, from a clinical and a radiological standpoint, the all-arthroscopic transosseous rotator cuff repair with cortical lateral augmentation, performed in the setting of a revision surgery. Eleven consecutive cases were prospectively followed up for a minimum of 12 month after a rotator cuff repair with a novel all-arthroscopic transosseous rotator cuff repair. VAS and UCLA score and patients’ satisfaction with the outcomes were analyzed, along with MRI evolution of the repair. All patients underwent a standardized surgery and postoperative rehabilitation program. All patients showed a significant improvement in pain reduction and functional score. Satisfaction was achieved in 10 out of 11 cases, and only 1 case showed a minor discontinuous tendon signal on the 12-month MRI assessment. No complications were noted. Our results favor the use of the all-arthroscopic transosseous rotator cuff revision surgery with the 2MC configuration (double MC means the initials of the authors—MM and CC, who have originally described it). It appears to be safe and effective, providing good clinical, functional, and radiological results, with a very high patient satisfaction.