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Background: Circulating immune cells play a pathogenic role in multiple sclerosis (MS). However, the role of specific lymphocyte subpopulations is not unveiled yet, especially in progressive stages. We aimed to investigate lymphocyte changes during siponimod treatment in active secondary progressive MS (aSPMS) and their associations with clinical outcomes., Methods: We enrolled 46 aSPMS patients starting on siponimod treatment with at least 6 months of follow-up and two visits within the scheduled timeframes and 14 sex- and age-matched healthy controls (HCs). Clinical and laboratory data were collected retrospectively at baseline, 3rd, 6th, 12th, and 24th month for MS patients, and at baseline for HCs., Results: At baseline SPMS patients presented with increased naïve regulatory T lymphocytes (p = 0.02) vs. HCs. Over time, SPMS patients showed decreased T CD4+ (coeff. range = -24/-17, 95% CI range = -31.60 to -10.40), B lymphocyte (coeff. range = -3.77/-2.54, 95% CI range = -6.02 to -0.35), memory regulatory B cells (coeff. range = -0.78/-0.57, 95% CI range = -1.24 to -0.17) and CD4/CD8 ratio (coeff. range = -4.44/-0.67, 95% CI range = -1.61 to -0.17) from month 3 thereafter vs. baseline, and reduced CD3+CD20+ lymphocytes from month 12 thereafter (coeff. range = -0.32/-0.24, 95% CI range = -0.59 to -0.03). Patients not experiencing disability progression while on siponimod treatment showed B lymphocyte reduction from month 3 (coeff. range = -4.23/-2.32, 95% CI range = -7.53 to -0.15) and CD3+CD20+ lymphocyte reduction from month 12 (coeff. range = -0.32/-0.24, 95% CI range = -0.59 to -0.03) vs. patients experiencing progression., Conclusions: Patients treated with siponimod showed a T and B lymphocyte reduction, especially CD4+, CD3+CD20+ and naïve regulatory T cells and memory regulatory B cells. Disability progression while on siponimod treatment was associated with a less pronounced effect on B and CD3+CD20+ lymphocytes., (© 2024. The Author(s).)

Background: Transforaminal lumbar interbody fusion (TLIF), a commonly used procedure in spine surgery, has the advantage of a lower incidence of nerve lesions compared to the posterior lumbar interbody fusion (PLIF) technique. The intersomatic arthrodesis has always been carried out with a single tantalum cage normally used for PLIF. Tantalum is a metal that is particularly used in orthopedic surgery. It has a modulus of elasticity similar to marrow and leads to high primary stability of the implant., Materials and Methods: Our study was a retrospective monocentric observational study evaluating clinical and radiological outcomes of tantalum cages in a modified TLIF technique with posterior instrumentation and autologous and/or homologous posterolateral bone grafting. The aim of the study was to evaluate clinical outcomes and the increase in or redistribution of lumbar lordosis. The intersomatic arthrodesis was always carried out with a single tantalum cage normally used for PLIF to reduce the neurological risk. We retrospectively studied 105 patients who were treated with a modified unilateral TLIF approach by two surgeons between 2013 and 2018. We evaluated the Oswestry Disability Index (ODI), Visual Analogue Scale (VAS) for back pain, global lumbar lordosis, lordosis of L4-sacrum, segmental lordosis of functional motion units that underwent arthrodesis, pelvic tilt, pelvic incidence, and the sacral slope in 77 patients. All patients were suffering from grade III or IV Pfirrmann, instability, or foraminal post-laminectomy stenosis and/or grade I-II degenerative spondylolisthesis or low-grade isthmic spondylolisthesis. They had no significant sagittal imbalance, with a sagittal vertical axis (SVA) of < 5 mm. The average follow-up duration was 30 months., Results: We achieved excellent clinical results, with only four cases of failure (5.2%). Moreover, we noticed a statistically significant redistribution of lumbar lordosis, with an average percentage increase in L4-S1 lordosis equal to 19.9% (P < 0.001), an average increase in the L4-S1/Lumbar lordosis (LL) ratio from 0.53 to 0.63 (P < 0.001), and a mean percentage increase in sacral slope equal to 7.6% (P < 0.001)., Conclusion: Thanks to the properties of tantalum, our modified single-portal TLIF technique is a valid surgical solution to obtain a solid arthrodesis and restore the correct lumbar lordosis distribution while reducing neurological complications and the number of failures., Level of Evidence: 4 Trial registration statement: retrospective observational study, no trial registration., (© 2023. The Author(s).)

Gain-of-function mutations in PIEZO1 cause dehydrated hereditary stomatocytosis (DHS) or hereditary xerocytosis, an autosomal dominant hemolytic anemia characterized by high reticulocyte count, a tendency to macrocytosis, and mild jaundice, as well as by other variably penetrant clinical features, such as perinatal edema, severe thromboembolic complications after splenectomy, and hepatic iron overload. PIEZO1 mutations in DHS lead to slowed inactivation kinetics of the ion channel and/or facilitation of channel opening in response to physiological stimuli. To characterize the alterations of red blood cell proteome in patients with mutated PIEZO1, we used a differential approach to compare the proteome of patients with DHS (16 patients from 13 unrelated ancestries) vs healthy individuals. We identified new components in the regulation of the complex landscape of erythrocytes ion and volume balance mediated by PIEZO1. Specifically, the main impaired processes in patients with DHS were ion homeostasis, transmembrane transport, regulation of vesicle-mediated transport, and the proteasomal catabolic process. Functional assays demonstrated coexpression of PIEZO1 and band 3 when PIEZO1 was activated. Moreover, the alteration of the vesicle-mediated transport was functionally demonstrated by an increased vesiculation rate in patients with DHS compared with healthy controls. This finding also provides an explanation of the pathogenetic mechanism underlying the increased thrombotic rate observed in these patients. Finally, the newly identified proteins, involved in the intracellular signaling pathways altered by PIEZO1 mutations, could be used in the future as potential druggable targets in DHS., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Objective: We aim to evaluate 3-year effects of ocrelizumab (humanized anti-CD20 monoclonal antibody for the treatment of multiple sclerosis (MS)) on lymphocytes, neutrophils and immunoglobulins: (1) when compared with pre-infusion assessment; (2) over the course of treatment; and (3) possible clinical correlates of the observed immunological modifications., Methods: This real-world observational cohort study has been conducted on prospectively collected data from 78 MS patients (mean age 47.8 ± 10.5 years; females 48.7%) commencing on ocrelizumab from 2018, with mean follow-up of 36.5 ± 6.8 months. Clinical data and blood samples were collected every three months. Total lymphocyte count and subpopulations were assessed on peripheral blood using flow cytometry. Serum immunoglobulins were evaluated with nephelometry., Results: When compared with pre-infusion values, we observed reduction of total, CD19 and CD20 lymphocyte counts; however, after the first infusion, their levels remained substantially stable. Over time we observed a progressive reduction of CD8 lymphocytes, while no changes were observed for CD4, CD27, CD3CD27, and CD19CD27. After the first infusion, we observed reduction in IgG, which further decreased during the follow-up. Higher probability of EDSS progression was associated with reduced modulation of CD8 lymphocytes., Interpretation: Ocrelizumab affects both humoral and cellular immune responses. Disability progression over the follow-up was associated with lower CD8 cytotoxic T-lymphocyte reduction. Changes in humoral response are immediate and sustained, while modulation of cellular immunity occurs progressively through regular re-treatment, and is related to clinical stability., (© 2022. The Author(s).)

Purpose: Arthroscopic ankle arthrodesis is known to offer high fusion rates, improvements in pain and functional outcomes, low risks of complications, and reinterventions. The aim of this study is to compare open vs. arthroscopic ankle arthrodesis in patients at high risk of complications., Methods: A single-centre retrospective comparative analysis of ankle fusions was conducted. Patient records were screened for demographics, type of arthrodesis, follow-up length, pre-operative diagnosis, risk factors for non-union, operative time, radiographic union, time to union, complications, and reinterventions. The American Orthopedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Scale, the Italian version of the Foot Function Index (FFI), and a visual analog scale (VAS) for pain scores collected pre-operatively and in the last follow-up were used to assess clinical outcomes., Results: There were 23 open and 21 arthroscopic ankle fusions. Union rate was higher (90.5% vs. 65.2%, p < 0.05) and complication rate was lower (14.3% vs. 47.8%, p < 0.05) in the arthroscopic group. In addition, patients who underwent arthroscopic arthrodesis reported better pain control, with higher improvements in VAS for pain scores. There was no significant difference in length of operative time, time to fusion, AOFAS, and FFI scores improvements between the two groups., Conclusions: Arthroscopic ankle arthrodesis resulted in higher union rates, fewer complications, and lower reoperation rates in patients at high risk of complications., (© 2021. The Author(s), under exclusive licence to The Author(s) under exclusive licence to SICOT aisbl.)

Periprosthetic joint infection (PJI) is one of the most challenging complications a surgeon has to face after prosthetic replacement of a joint and one of the most devastating complications for the patient. During the 2018 International Consensus Meeting (ICM) in Philadelphia a numerical diagnostic tool was proposed. Contraindications to single stage revision include significant soft tissue injury with the inability to provide soft tissue cover, the presence of unknown or multi resistant organisms, lack of access to appropriate antibiotics or lack of appropriate expertise. Two stage revision surgery is indicated in these situations. Insall et al. described the surgical two-stage prosthetic revision technique in 1983: the in situ prosthesis is removed, a thorough debridement of bone and soft tissue is performed, an interval spacer is inserted, antibiotics administered. The 2 nd stage of definitive reconstruction is performed once the infection is deemed to have resolved. The interval between stages can range from 6 weeks to several months. PJI are very challenging for every surgeon skilled in prosthetic surgery. It's necessary to make an exact preoperative diagnosis and to treat them with the proper technique. Further studies are needed to establish the perfect timing between the two stages, the duration of the antibiotic therapy and to standardize the diagnostic chart., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/aoj-20-84). The series “Prosthetic Joint Infection” was commissioned by the editorial office without any funding or sponsorship. MF and NAS served as the unpaid Guest Editors of the series. The authors have no other conflicts of interest to declare., (2022 Annals of Joint. All rights reserved.)

Background: Surgical reconstruction of chronic wounds is often infeasible due to infection, comorbidities, or poor viability of local tissues. The aim of this study was to describe the authors' technique for improving the regenerative and antimicrobial potential of a combination of modified nanofat and platelet-rich plasma (PRP) in nonhealing infected wounds., Methods: Fourteen patients met the inclusion criteria. Fat tissue was harvested from the lower abdomen following infiltration of a solution of 1,000 mL of NaCl solution, 225 mg of ropivacaine, and 1 mg of epinephrine. Aspiration was performed using a 3-mm cannula with 1-mm holes. The obtained solution was decanted and mechanically emulsified, but was not filtered. Non-activated leukocyte-rich PRP (naLR-PRP) was added to the solution before injection. Patients underwent three sessions of injection of 8-mL naLR-PRP performed at 2-week intervals., Results: Thirteen of 14 patients completed the follow-up. Complete healing was achieved in seven patients (53.8%). Four patients (30.8%) showed improvement, with a mean ulcer width reduction of 57.5%±13.8%. Clinical improvements in perilesional skin quality were reported in all patients, with reduced erythema, increased thickness, and increased pliability. An overall wound depth reduction of 76.6%±40.8% was found. Pain was fully alleviated in all patients who underwent re-epithelization. A mean pain reduction of 42%±33.3% (as indicated by visual analog scale score) was found in non-re-epithelized patients at a 3-month follow-up., Conclusions: The discussed technique facilitated improvement of both the regenerative and the antimicrobial potential of fat grafting. It proved effective in surgically-untreatable infected chronic wounds unresponsive to conventional therapies.

A 62-year-old male patient with diabetes underwent deceased-donor kidney transplant at our transplant unit. At reperfusion, a small and clinically not significant subcapsular hematoma was noted. The patient's postoperative course was characterized by delayed graft function since the beginning but was further complicated on postoperative day 6 by evidence (shown at daily Doppler ultrasonography) of a wide increase of the hematoma. The hematoma, which was just visible before, was now leading to graft compression because it covered up to two-thirds of the cortical surface. The patient showed no hemo-dynamic instability and showed no significant drop in hemoglobin values. Capsulotomy was not performed because it was deemed too risky. The patient was given strict follow-up with Doppler ultrasonography and high-resolution imaging techniques (magnetic resonance imaging and computed tomography scan). In the following days, spontaneous resolution of the hematoma and progressive improvement of Doppler findings were observed, which preceded full recovery of graft function. Conservative management, in hemodynamically stable patients, seems to be a valid approach of this condition. By avoiding surgery or other interventional procedures, a conservative approach allows reduced risk of further complications. Strict monitoring with Doppler ultrasonography is a valid tool for follow-up, along with high-resolution imaging techniques such as magnetic resonance imaging and computed tomography to confirm diagnosis.

Background: Nonsurgical rhinoplasty with hyaluronic acid (HA) has gained popularity due to its efficacy and minimal downtime. From a structural standpoint, it is like performing a tridimensional reshaping where only enhancement by grafts is allowed. To date, indications, technique, and products are still debated. The aim of this study is to describe the author's experience with nonsurgical nasal reshaping, focusing on the indications and maneuvers to safely achieve, by mean of HA, the grafts previously described for surgical rhinoplasty., Materials and Methods: A total of 70 consecutive patients underwent nonsurgical rhinoplasty using the same type of HA. The rhinoplasty module of FACE-Q was administered to all patients before treatment and 15 days posttreatment. Statistical analysis was performed., Results: No complication was experienced. Two (2.8%) patients required a retouch after 15 days for further dorsal correction. There was a statistically significant difference between preoperative and postoperative values in all domains and overall scores of the rhinoplasty module of FACE-Q., Conclusions: The graft-based technique proved to be safe, effective, and reliable. It may allow correction of selected nasal defects with reduced cost and minimal downtime., (Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Adult flatfoot is a common pathology characterized by multiplanar deformity involving hindfoot, midfoot, and forefoot. Various surgical techniques have been described for the treatment but may not adequately correct the fixed forefoot varus component. Residual forefoot supination can be addressed by a plantar flexing opening wedge osteotomy of the medial cuneiform, also known as a Cotton osteotomy. Thus, the aims of this study were to compare clinical, radiological, and functional outcome after Cotton osteotomy, in patients treated with bone allograft or metallic implant. Consequently, 36 patients treated with opening wedge osteotomy of the medial cuneiform for forefoot varus were studied retrospectively. Patients were divided into two groups: the bone allograft group (HBG) (n=18) and the metallic implant group with BIOFOAM® Cotton Wedges (TTW) (n=18). Radiographic assessment and clinical scores including American Orthopaedic Foot and Ankle Society score, Foot Function Index, and visual analogue scale for pain were collected before operation and the last follow-up. The difference between baseline and follow-up for both groups was statistically significant for all the clinical scores and radiographic angles (p < 0.05). Most participants (92%) were very satisfied after surgery. Our results showed that Cotton osteotomy with a metallic implant provided both good clinical and radiographic outcomes comparable with bone allograft.

Background: recently, healthcare network models have been proposed to improve general awareness of rare diseases for patients and specific knowledge about diagnosis, treatment, and management for healthcare services. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare haematological disease that still has no framing in an official network., Objectives: to describe the use of network models in diagnosis, treatment, and management of PNH patients both in Italy and abroad and its impact on patients and healthcare service. DISEGN: literature search was performed using the keywords "Hemoglobinuria", "Network", "PHN", and "Screening" in both MedLine and EMBASE. Search was restricted to the articles published in the last 5 years and written in English, French or Italian language., Results: from the total 251 articles of the initial search, only 21 were finally included in our review. None of the included study explicitly described a network model. In general, we were able to identify two different kind of networks implicitly described in the studies: laboratory networks for diagnostic harmonization or screening of the population at risk of PNH (10/21 studies) and PNH registry as network of clinical information to be use for better understanding of the natural history of the disease and to assess therapeutic effectiveness (11/21 studies)., Conclusions: few network approaches in PNH diagnosis, treatment, and management are described in literature. Despite the scarce application of the networks, our review highlights the positive impact that networks have in both patients and healthcare services.

Background: Few studies in the recent literature have investigated the reliability of dorsal intercostal artery perforator (DICAP) flap in posterior trunk reconstruction. The purpose of this report is to describe our clinical experience with the use of DICAP flaps in a cohort of oncological patients., Patients and Methods: Twenty patients underwent posterior trunk reconstruction with DICAP based flaps. Patients age ranged from 45 to 76 years. All defects resulted from skin cancer ablation. Defect sizes ranged from 4 × 4 to 6 × 8 cm. The flaps were mobilized in V-Y or propeller fashion. The flaps were islanded on 1 (12 cases), 2 (6 cases), or 3 (2 cases) perforators. Donor sites were always closed primarily., Results: Eleven V-Y advancement flaps were performed; one of these was converted to a perforator-plus peninsular flap design, which retained an additional source of blood supply from the opposite skin bridge. Nine flaps were mobilized in propeller fashion. Flap dimensions ranged from 4 × 6 to 6 × 14 cm. Mean operative time was 70 min. One V-Y flap complicated with marginal necrosis that healed with no need for reintervention. All the other flaps survived uneventfully. No other complications were observed at recipient and donor sites. Follow-up ranged from 3 months to 2 years. All the patients were satisfied with the surgical outcome., Conclusions: DICAP based flaps proved to be a reliable option to resurface posterior trunk defects following oncological resection, allowing to achieve like-with-like reconstruction with excellent contour and minimal donor-site morbidity. © 2015 Wiley Periodicals, Inc. Microsurgery 36:546-551, 2016., (© 2015 Wiley Periodicals, Inc.)

Raynaud phenomenon (RP) is a transient digital ischemia that occurs after exposure to cold temperature or emotional distress. It presents with a triphasic course: the initial white phase is followed by cyanotic discoloration and, subsequently, erythema. The attacks may be associated with pain, paresthesia, and complicate with nonhealing ulceration often leading to amputation. To date, there are no clear-cut therapeutic guidelines and many medications are used off-label. Encouraging results were reported with the use of botulinum neurotoxin-A (BoNT-A). However, there is still ongoing debate regarding indications, contraindications, best injection technique, and mechanism of action. The aim of this study was to address these issues by providing an up-to-date and detailed overview of the use of BoNT-A in RP.A PubMed database search was conducted. The available studies and techniques were evaluated and compared.The search yielded a total of 29 studies. Ten papers, published between 2004 and 2014, were considered relevant. A total of 128 patients underwent BoNT-A injections. Seventy-five percent to 100 % of the patients reported pain reduction after treatment. Healing of ulcers was reported in 75% to 100% of the affected patients. The most common complication was temporary hand weakness, with an average incidence of 14.1%. Injections targeting the neurovascular bundle at or slightly proximal to the A1 pulley were the most commonly performed.Botulinum neurotoxin-A injection proved to be a valid approach in both primary and secondary RP. The available evidence shows the achievement of both symptomatic and functional improvements in this debilitating condition. However, the patient should be adequately informed about the risk of transient hand weakness.

Background: A primary lymph node leiomyoma diagnosed by fine needle aspiration cytology (FNAC) is reported., Case: A 22-year-old male complained of right groin swelling; ultrasound examination (US) showed a lymph node containing a 20-mm hypoechoic nodule. The residual lymph node was oval, with a well-characterized cortex and hilum. US-FNAC of the nodule showed oval spindle cells embedded in fibrillar matrix. Nuclei were naked and oval with dispersed chromatin but without nucleoli. Immunocytochemistry showed positivity for vimentin and actin, and negativity for cytokeratin, S100, CD23 and CD31. A smear of the residual lymph node showed a reactive lymphoid cell population. FNAC diagnosis was mesenchymal cell proliferation with smooth muscle phenotype; a lymph node is part of the lesion. A CT scan did not detect any inguinal or abdominal mass. The surgical sample was a lymph node containing a spindle cell tumor, which was actin and desmin positive, and S100, CD21, HMB45, CD23 and CD31 negative; MIB1 was positive in <5% of the cells. The residual lymph node was normal., Conclusion: The final diagnosis was primary benign leiomyoma in a lymph node. US-FNAC may frame complex lymph node lesions and provide treatment options., (© 2014 S. Karger AG, Basel.)

We report the thirteenth case of a rectourethral fistula in Crohn's disease. The patient, a 37 year-old-white male, had a 20 year history of intestinal Crohn's disease and had undergone numerous bowel resections. His symptoms were fecaluria, urorrhea and passing of urine from an orifice just outside the base of the scrotum. He had urinary infection and severe ileocolitis. He underwent a diagnostic evaluation that revealed a fistula comprising the membranous urethra, the rectum, the perineum and the scrotum. We performed medical therapy with metronidazole (20 mg/kg/day/12 months). We present in this article a review of the literature on the management of rectourethral fistulas in Crohn's disease. Surgeons have successfully used several approaches in the repair of this disorder, but no single procedure had proved to be best or even universally applicable. We emphasize, as the literature suggests, that management must be individualized. Medical therapy with metronidazole has an important role in a patient with rectourethral fistula and concomitant proctitis, ileocolitis, urinary sepsis and multiple previous surgeries.

The AA. report their experience as to the treatment applied to patients suffering from unremovable bronchial cancers. They can therefore stress the results obtained by chemotherapeutic treatment associated to thymopentin as well as interferon-thymopentin treatment. Elderly patients were subjected to interferon-thymopentin therapy, which helped in improving their life standard and survival.

The authors studied the cases of pulmonary tuberculosis they had the opportunity to observe during a five-year period from 1985 to 1989 carrying out the phenomenon. As a result they pointed out that the worst affected subjects belonged to the age bands included between the second and the third decade, followed by the fifth decade and over. They concluded that the 234 cases they examined do not represent the real number of affected subjects and that elderly patients to the most serious cases.