Homozygous mutation in the prokineticin-receptor2 gene (Val274Asp) presenting as reversible Kallmann syndrome and persistent oligozoospermia: case report.

Prokineticin 2 (Prok2) or prokineticin-receptor2 (Prok-R2) gene mutations are associated with Kallmann syndrome (KS). We describe a new homozygous mutation of Prok-R2 gene in a man displaying KS with an apparent reversal of hypogonadism. The proband, offspring of consanguineous parents, presented at age 19 years with absent puberty, no sense of smell, low testosterone and gonadotrophin levels. Magnetic resonance imaging showed olfactory bulb absence. The patient achieved virilization and spermatogenesis with gonadotrophin administration. Two years after discontinuing hormonal therapy, he maintained moderate oligozoospermia and normal testosterone levels. Prok2 and Prok- R2 gene sequence analyses were performed. The proband had a homozygous mutation in Prok-R2 exon 2 that harbours the c.T820>A base substitution, causing the introduction of an aspartic acid in place of valine at position 274 (Val274Asp). His mother had the same mutation in heterozygous state. This report describes a novel homozygous mutation of Prok-R2 gene in a man with variant KS, underlying the role of Prok-R2 gene in the olfactory and reproductive system development in humans. Present findings indicate that markedly delayed activation of gonadotrophin secretion may occur in some KS cases with definite gene defects, and that oligozoospermia might result from a variant form of reversible hypogonadotrophic hypogonadism

Hip viscosupplementation under ultra-sound guidance riduces NSAID consumption in symptomatic hip osteoarthritis patients in a long follow-up. Data from Italian registry.

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) consumption is strictly related to a high gastrointestinal and cardiovascular mortality and morbidity rate. Osteoarthritis Research Society International (OARSI) recommendations in patients with symptomatic hip or knee OA stated that NSAIDs should be used at the lowest effective dose but their long-term use should be avoided if possible. OARSI guidelines for the treatment of the hip OA include the use of viscosupplementation, which aims to restore physiological and Theological features of the synovial fluid. Objective: Aim of this multicentric, open and retrospective study is to investigate if NSAID consumption may be reduced by the use of ultrasound-guided intra-articular injection of several hyaluronic acid (HA) products in hip joint administered in patients affected by symptomatic hip OA. Materials and Methods: Patients affected by mono or bilateral symptomatic hip OA according to American Rheumatology Association (ARA) criteria, radiological OA graded II-IV (Kellgren and Lawrence) entered the study and were administered with ultrasound-guided intra-articular injection of hyaluronic acid products. As a primary endpoint, consumption of NSAIDs was evaluated by recording the number of days a month (range 0-30) the patient had used NSAID during the previous month, reported at each visit during the 24 months follow-up period. Secondary endpoints included further analysis for subgroups of patients categorized for Lequesne index score, Kellgren-Lawrence score, pain visual analogue scale (VAS) score, ultrasound pattern, age, hyaluronic acid used. Results: 2343 patients entered the study. Regarding primary endpoint, the consumption of NSAIDs was reduced of 48.2% at the third month when compared with baseline values. This sparing effect increased at 12th and 24th month with a reduction respectively of 50% and 61% in comparison to baseline values. These differences were statistically significant. Conclusions: These data point out that intraarticular hyaluronan preparations provide OA pain relief and reduce NSAIDs consumption in a large cohort of patients for a long period of follow-up. Multiple courses of viscosupplementation (vs) are required to maintain low dose of NSAID consumption over time. NSAIDs consumption is strictly related to an high gastrointestinal and cardiovascular mortality and morbidity rate, instead HA intra-articular treatment is well tolerated and is associated with a low incidence of adverse effects. For these reasons further studies evaluating cost-effectiveness and cost-utility of VS in the management of hip OA are required

Complex regional pain syndrome in athletes: Scoping review

Background and Objectives: Complex regional pain syndrome (CRPS) is a chronic condition characterized by disproportionate regional pain, usually affecting distal limbs, that follows trauma or surgery. Athletes may develop CRPS because of exposure to traumatic or overuse injuries. The aim of the present study is to review the available literature about CRPS type 1 in athletes. Materials and Methods: We searched two online databases (PubMed and Web of Science), selecting papers aiming at investigating CRPS type 1 (algodystrophy) in athletes. The analysis of databases was made considering original articles published until 30 June 2021, written in English. Results: Fifteen papers (12 case reports, 3 case series) were selected for a total of 20 clinical cases (15 females, 5 males), aged between 10 and 46 years (mean age 18.4 ± 9.8 standard deviation years). Patients included practiced different types of sport (soccer, athletics, gymnastics, basketball). The most involved anatomical sites were lower limbs, and time to diagnosis ranged from 2 days to 4 years. The most used treatments were pharmacological and physical therapies, but sometimes invasive approaches, as regional nerve, or lumbar sympathetic blocks, were provided. The main assessed outcomes were return to activity and pain. Conclusions: Our review suggests a higher prevalence of CRPS type 1 in younger people and in lower limbs than in general population but confirms the higher prevalence in females. However, the number of studies addressing CRPS in athletes is limited, as well as the number of involved patients, considering that only few and heterogeneous case reports were published about this topic. Moreover, the high prevalence of old studies (only 5 available studies in the last 10 years) might have influenced the choice of both assessment tools and management strategies. Despite these limitations, athletes showing disproportionate pain after sport-related injury should be promptly evaluated and treated through a multidimensional approach to avoid long-term consequences of algodystrophy

Protein deficiency balance as a predictor of clinical outcome in hereditary spherocytosis

Vertical and horizontal interactions between membrane constituents account for integrity, strength and deformability of the erythrocyte. Disruption of vertical interactions caused by membrane protein deficiencies in hereditary spherocytosis (HS), favor membrane vesiculation with development of spherocytic cells. Our aim was to evaluate the hematological and clinical presentation of HS according to the type and amount of protein deficiency. We studied 81 Portuguese individuals, 71 belonging to 21 families plus 10 unrelated subjects, and found that 51 of them were HS patients. Patients were classified as presenting mild, typical or severe HS, according to laboratory results and clinical follow-up. We performed screening tests and the standardized electrophoretic membrane protein analysis to identify and quantify protein deficiencies. We found band 3 and ankyrin deficiencies as the major causes for HS. The ratios between the value of the primary and/or secondary protein deficiencies showed significantly different values according to the severity of HS, and a significant inverse correlation with the severity of HS was observed. In mild HS, the ratios between protein deficiencies reflected equivalent protein deficiencies, while an unbalance was observed in typical HS, which was enhanced in severe HS. Our data suggest that the relative quantification of each major membrane protein and of the ratios between the values of protein deficiencies may be helpful in providing additional data about the clinical outcome of HS

Efficacy and Effectiveness of Extracorporeal Shockwave Therapy in Patients with Myofascial Pain or Fibromyalgia: A Scoping Review

Myofascial pain syndrome (MPS) and fibromyalgia (FM) are underestimated painful musculoskeletal conditions that could impact function and quality of life. A consensus about the most appropriate therapeutic approach is still not reached. Considering the long course of the diseases, prolonged assumption of drugs, such as NSAIDs and pain killers, could increase the risk of adverse events, often leading affected patients and physicians to prefer non-pharmacological approaches. Among these, radial and focused extracorporeal shock waves therapies (ESWT) are widely used in the management of painful musculoskeletal conditions, despite the fact that the mechanisms of action in the context of pain modulation should be further clarified. We performed a scoping review on PubMed using Mesh terms for analyzing the current evidence about the efficacy and effectiveness of ESWT for patients with MPS or FM. We included 19 clinical studies (randomized controlled trials and observational studies); 12 used radial ESWT, and 7 used focused ESWT for MPS. Qualitative analysis suggests a beneficial role of ESWT for improving clinical and functional outcomes in people with MPS, whereas no evidence was found for FM. Considering this research gap, we finally suggested a therapeutic protocol for this latter condition according to the most recent diagnostic criteria

A novel PIEZO1 mutation in a patient with dehydrated hereditary stomatocytosis: A case report and a brief review of literature

open7noThis work was supported by EHA Junior Research Grant to Immacolata Andolfo (3978026), and by Bando Star Linea 1 - JUNIOR PRINCIPAL INVESTIGATOR GRANTS - COINOR, Università degli Studi di Napoli Federico II to Roberta Russo.Background: Dehydrated hereditary stomatocytosis (DHS) or hereditary xerocytosis is a rare, autosomal dominant hemolytic anemia characterized by macrocytosis, presence of stomatocytes and dehydration of red blood cells (RBCs). The dehydration is caused by a defect in cellular cation content. The most frequent expression of the pathology is hemolytic well-compensated anemia with high reticulocyte count, a tendency to macrocytosis, increased mean corpuscular hemoglobin concentration (MCHC) and mild jaundice. We here describe a new mutation of PIEZO1 gene, the most frequent mutated gene in DHS, in a family affected by hereditary hemolytic anemia. Case presentation: We describe the case of a 12-years-old girl with well-compensated chronic hemolysis, increased MCHC and a father who had the same hematological characteristics. After excluding secondary causes of chronic hemolysis and enzymatic defects of the RBCs, microscopic observation of the peripheral blood smear, tests of RBC lysis, ektacytometry, SDS-PAGE and in last instance genetic analysis has been performed. This complex diagnostic workup identified a new variant in the PIEZO1 gene, never described in literature, causative of DHS. This pathogenetic variant was also detected in the father. Conclusions: This case report highlights the importance of a correct and exhaustive diagnostic-workup in patients with clinical suspicious for hemolytic anemia in order to make a differential diagnosis. This is relevant for the management of these patients because splenectomy is contraindicated in DHS due to high thrombotic risk.openZama D.; Giulietti G.; Muratore E.; Andolfo I.; Russo R.; Iolascon A.; Pession A.Zama D.; Giulietti G.; Muratore E.; Andolfo I.; Russo R.; Iolascon A.; Pession A

Post-acute covid-19 rehabilitation network proposal: From intensive to extensive and home-based it supported services

Management of COVID-19 post-acute syndrome is an emerging health issue in rehabilitation. This article aims to present a proposal, based on the principles of clinical governance, health management and information technology (IT), and to respond to the need for a structured organization model for post-acute COVID-19 rehabilitation. The authors present a regional-based model of a network of clinicians and healthcare managers using a dedicated IT platform to achieve both effectiveness and efficiency objectives, to ensure coordination of the available resources and the most appropriate rehabilitative treatment for patients. The proposed post-acute COVID-19 rehabilitation network has been designed according to the model of a clinical management project within the Italian national healthcare system, and its context is an easily adjustable model for the European healthcare systems. The authors base the project on current laws and scientific guidelines in rehabilitation in Italy and in Europe and use the SWOT analysis technique to assess the proposal feasibility. The primary aims of the project are: (1) standardizing the minimum assessment tools of post-COVID-19 patients with disabilities; (2) ensuring an individual rehabilitation project for each patient with international classification of functioning, disability and health (ICF) coding and (3) reporting the activity performance with appropriate indicators. The secondary aims are: (1) developing educational programs for patients and care givers also aimed at acquiring better empowerment and positive behavior; (2) creating a regional database for data collection and (3) improving IT, and specifically tele-rehabilitation, as a suitable approach during the COVID-19 emergency and also in the future. Expected results are: continuum of care; effectiveness, efficacy and appropriateness in the delivery of rehabilitation treatments through a standardized minimum assessment and the wording of the individual rehabilitation project and a precise reporting of performance indicators to measure the effectiveness of clinical activities and the satisfaction of patients and caregivers. The assessment of results will be analyzed at three and six months to implement corrective actions according to the concept of continuous improvement of the Deming cycle. The IT remote approach allows the patient to meet the needs of proximity of care and empowerment, and, at the same time, to contain the spread of infection. This project could have a significant healthcare impact ensuring a more efficient and effective management of the demand of rehabilitation post-acute COVID-19, expanding the professional skills of the rehabilitation team members, improving both clinical and process data, in addition to optimal allocation of available economic resources

Osteosarcopenia and type 2 diabetes mellitus in post-menopausal women: a case-control study

Background Osteosarcopenia has been defined as the concomitance of low bone density (osteopenia/ osteoporosis) and sarcopenia. Osteoporosis is characterized by alterations in bone microarchitecture and decrease of bone mineral density (BMD), whereas sarcopenia is the progressive decrease of both muscle mass and function that increase the risk of falls. Type 2 diabetes mellitus (T2DM) is associated with poor bone strength and muscle wasting. Objective The aim of this study is to analyze the association between osteosarcopenia and T2DM in post-menopausal women (PMW). Methods We performed an age matched case-control study (1:2 ratio), considering as cases PMW affected by T2DM, and PMW without T2DM as control group. For all patients a DXA evaluation to investigate bone density and body composition measures were performed. Moreover, we carried out muscle strength and performance assessments. Outcome measures were femoral neck and lumbar spine BMD T-scores, appendicular lean mass (ALM), handgrip strength and the Short Physical Performance Battery (SPPB). Data from both groups were analyzed and compared. Results Thirty-six PMW (12 T2DM vs 24 non-T2DM) were recruited. The frequency of osteosarcopenia was significantly higher in the T2DM group compared to controls (50% vs 17%; OR 5.0, 95% CI 1.05 to 23.79, p = 0.043). Handgrip strength was significantly lower in the T2DM group (10.09 ± 4.02 kg vs 18.40 ± 6.83 kg; p = 0.001). Conclusions Post-menopausal women with T2DM have a 5 times higher risk to have osteosarcopenia compared to non-diabetic ones. Further studies on larger cohorts are required to confirm these findings