Guidelines How to Integrate Surgery and Targeted Therapy with Biologics for the Treatment of Hidradenitis Suppurativa: Delphi Consensus Statements from an Italian Expert Panel.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent and painful nodules and abscesses in intertriginous skin areas, which can progress to sinus tract formation, tissue destruction, and scarring. HS is highly debilitating and severely impairs the psychological well-being and quality of life of patients. The therapeutic approach to HS is based on medical therapy and surgery. First-line medical therapy includes topical antibiotics, systemic antibiotics, and biologics. Main surgical procedures include deroofing, local excision, and wide local excision. Despite the availability of multiple therapeutic options, the rates of disease recurrence and progression continue to be high. In recent years, the possibility of combining biologic therapy and surgery has raised considerable interest. In a clinical trial, the perioperative use of adalimumab has been associated with greater response rates and improved inflammatory load and pain, with no increased risk of postoperative infectious complications. However, several practical aspects of combined biologic therapy and surgery are poorly defined. In June 2022, nine Italian HS experts convened to address issues related to the integration of biologic therapy and surgery in clinical practice. To this purpose, the experts identified 10 areas of interest based on published evidence and personal experience: (1) patient profiling (diagnostic criteria, disease severity classification, assessment of response to treatment, patient-reported outcomes, comorbidities); (2) tailoring surgery to HS characteristics; (3) wide local excision; (4) presurgery biologic treatment; (5) concomitant biologic and surgical treatments; (6) pre- and postsurgery management; (7) antibiotic systemic therapy; (8) biologic therapy after radical surgery; (9) management of adverse events to biologics; and (10) management of postoperative infectious complications. Consensus between experts was reached using the Estimate-Talk-Estimate method (Delphi Method). The statements were subsequently presented to a panel of 27 HS experts from across Italy, and their agreement was assessed using the UCLA Appropriateness Method. This article presents and discusses the consensus statements.

Bone Regeneration Guided by a Magnetized Scaffold in an Ovine Defect Model.

The reconstruction of large segmental defects still represents a critical issue in the orthopedic field. The use of functionalized scaffolds able to create a magnetic environment is a fascinating option to guide the onset of regenerative processes. In the present study, a porous hydroxyapatite scaffold, incorporating superparamagnetic Fe3O4 nanoparticles (MNPs), was implanted in a critical bone defect realized in sheep metatarsus. Superparamagnetic nanoparticles functionalized with hyperbranched poly(epsilon-Lysine) peptides and physically complexed with vascular endothelial growth factor (VEGF) where injected in situ to penetrate the magnetic scaffold. The scaffold was fixed with cylindrical permanent NdFeB magnets implanted proximally, and the magnetic forces generated by the magnets enabled the capture of the injected nanoparticles forming a VEGF gradient in its porosity. After 16 weeks, histomorphometric measurements were performed to quantify bone growth and bone-to-implant contact, while the mechanical properties of regenerated bone via an atomic force microscopy (AFM) analysis were investigated. The results showed increased bone regeneration at the magnetized interface; this regeneration was higher in the VEGF-MNP-treated group, while the nanomechanical behavior of the tissue was similar to the pattern of the magnetic field distribution. This new approach provides insights into the ability of magnetic technologies to stimulate bone formation, improving bone/scaffold interaction.

Functional dosing of mesenchymal stromal cell-derived extracellular vesicles for the prevention of acute graft-versus-host-disease.

Graft-vs-host-disease (GvHD) is currently the main complication of allogeneic hematopoietic stem cell transplantation. Mortality and morbidity rates are particularly high, especially in steroid-refractory acute GvHD (aGvHD). Immune regulatory human bone marrow mesenchymal stromal cells (hMB-MSCs) represent a therapeutic approach to address this issue. Unfortunately, their effect is hardly predictable in vivo due to several variables, that is, MSC tissue origin, concentration, dose number, administration route and timing, and inflammatory status of the recipient. Interestingly, human bone marrow MSC-derived extracellular vesicles (hBM-MSC-EVs) display many of the hBM-MSC immunoregulatory properties due to their content in paracrine factors that greatly varies according to the collection method. In this study, we focused on the immunological characterization of hBM-MSC-EVs on their capability of inducing regulatory T-cells (T-regs) both in vitro and in a xenograft mouse model of aGvHD. We correlated these data with the aGvHD incidence and degree following hBM-MSC-EV intravenous administration. Thus, we first quantified the EV immunomodulation in vitro in terms of EV immunomodulatory functional unit (EV-IFU), that is, the lowest concentration of EVs leading in vitro to at least threefold increase of the T-regs compared with controls. Second, we established the EV therapeutic dose in vivo (EV-TD) corresponding to 10-fold the in vitro EV-IFU. According to this approach, we observed a significant improvement of both mouse survival and control of aGvHD onset and progression. This study confirms that EVs may represent an alternative to whole MSCs for aGvHD prevention, once the effective dose is reproducibly identified according to EV-IFU and EV-TD definition.

Giant Centrifugal and Necrotizing Cutaneous Metastases of Melanoma: A Brief Review of the Literature and a Case Report.

BACKGROUND: Melanoma is a neoplasm derived from melanocytes of the skin and other sites. In the natural history of melanoma, cutaneous metastases occur relatively frequently and can arise in early or late stages of the disease. OBJECTIVE AND METHODS: Melanoma skin metastases have a variable appearance. Several clinical appearances are described in the literature. RESULTS AND CONCLUSION: We describe an unusual clinical pattern of cutaneous melanoma metastasis, defined as giant, centrifugal, and necrotizing, and we provide a brief review of the literature.

Cutaneous melanoma frequencies and seasonal trend in 20 years of observation of a population characterised by excessive sun exposure.

BACKGROUND: Cutaneous melanoma is an aggressive form of skin cancer. It has become an increasingly common neoplasm in the most developed countries, especially among individuals of European origin. PATIENTS AND METHODS: Anonymous data of patients with cutaneous melanoma were collected from the diagnostic database of the University Hospital of Trieste from 1 January 1990 to 10 December 2013. Our study is based on a population which was constant over the period of observation; it was also well-defined and characterised by unrestrained sun exposure. RESULTS: The number of cutaneous melanomas increased during the period of observation with a seasonality trend and gender related differences both for anatomical sites distribution and stage of the disease. Moreover, 6% of our cohort developed multiple melanomas. CONCLUSIONS: In a well-defined population devoted to excessive sun exposure the frequencies of skin melanomas roughly doubled from 1990 to 2013 following a seasonal trend. In that population, prevention efforts according to gender specific risk behaviour, as well as follow-up programmes both for evaluation of metastatic spreading and for early diagnosis of additional skin melanomas, are crucial due to gender specific differences and to the occurrence of multiple melanomas.

Electrochemotherapy as a novel treatment for primary cutaneous marginal zone B-cell lymphomas.

In the present study, we describe the use of electrochemotherapy as alternative therapy for primary cutaneous marginal zone B-cell lymphomas in patients unsuitable for surgery or radiotherapy. Our experience refers to three patients with primary cutaneous marginal zone B-cell lymphomas related to Borrelia burgdorferi infection, treated with specific antimicrobial therapy and electrochemotherapy.

Giant melanoma of the abdomen: case report and revision of the published cases.

Malignant melanoma presenting as a giant cutaneous mass is rarely observed in clinical practice. A few patients with giant melanoma have been reported, Herein, we document our experience with a patient with giant cutaneous melanoma of the abdomen and review the features of previously reported individuals.

"Who's Got Talent?" Change of Direction, Anthropometric Characteristics and Maturity Offset Differences Between Elite and Sub-Elite Young Soccer Player.

Agility, anthropometrics and maturity-offset have been considered fundamental for talent identification in soccer. The aim of this study is to compare 83 young soccer players (U12) from elite (28) and sub-elite (55) teams, to investigate the influences of anthropometric characteristics and maturation on Change-of-Direction (CoD) with the ball (dribbling) and without the ball. ANCOVA was run to investigate potential differences in Agility T-Test and Shuttle Dribble Test between categories while simultaneously controlling for the effects of anthropometric variables such as Peak Height Velocity (PHV), Weight, and Height. Agility T-Test performance does not significantly differ between the two categories (F-value = 0.537, p > .05). However, the Weight significantly influences the results (F-value = 18.425, p < .001, Eta-Squared = 0.172) and also PHV has a significant impact on them (F-value = 10.099, p < .01, Eta-Squared = 0.094). The Shuttle Dribble Test performance significantly varies between two groups (F-value = 5.207, p < .05, Eta-Squared = 0.057). Only Weight significantly influences this test (F-value = 4.324, p < .05, Eta-Squared = 0.048). Our findings indicate that during the U-12 age period, technical skills emerge as a crucial discriminant factor between elite and sub-elite young soccer players, contrarily to the athletic performance without the ball. In addition, the maturity stage specifically influences the Agility T-Test and Weight is significantly related to lower time to complete both in Agility T-Test and SDT.

Is change of direction influenced by motor competencies? A possible response from a MOBAK-based study in Italian schoolchildren.

BACKGROUND: Change of direction (COD) ability requires higher motor control capacity and helps children improve individual motor skills. Likewise, basic motor competencies (BMC) are relevant during child maturation and may interleave with COD ability. This study aimed to investigate the possible individual determinants between the COD ability and the BMC, cognitive skills, and anthropometrics characteristics in Italian primary school children aged 6 to 11. METHODS: Children of both sexes (N.=221) were recruited from primary schools (grade 1 to 5) of Northwestern Italy. COD was assessed by 10×5 m Shuttle Run Test; motor coordination by the Motor Coordination (Motorische Basiskompetenzen, MOBAK) 1-6 test battery, whereas Trail Making Test was used to assess cognitive performance. RESULTS: A stepwise linear regression indicated that motor competencies level - assessed by the MOBAK Test - is the most fitting dimension describing COD performance for girls, with the highest R2 in Grade 5 (SEE=0.56); and the lowest SEE in Grade 5 (SEE=1.44); moreover, for boys the highest in Grade 3 (SEE=0.52) and the lowest SEE in Grade 4 (SEE=1.30). CONCLUSIONS: This study confirms the biunivocal relationship between COD and BMC, and the need for physical education teachers and trainers to stimulate both, during growth.

Poor Motor Competence Affects Functional Capacities and Healthcare in Children and Adolescents with Obesity.

BACKGROUND: From a young age, children learn different motor skills known as fundamental motor skills. The acquisition of these skills is crucial for the future development of context-tailored actions that could improve adherence to physical activity (PA) practice. Motor competence and function deficits have been associated with pediatric obesity. We reviewed the literature data regarding motor competence in pediatrics and impaired motor performance in children and adolescents with obesity. METHODS: We assessed the abstracts of the available literature (n = 110) and reviewed the full texts of potentially relevant articles (n = 65) that were analyzed to provide a critical discussion. RESULTS: Children and adolescents with obesity show impaired motor performance, executive functions, postural control, and motor coordination. Children's age represents a crucial point in the development of motor skills. Early interventions are crucial to preventing declines in motor proficiency and impacting children's PA and overall fitness levels. CONCLUSIONS: To involve children, the PA protocol must be fun and tailored in consideration of several aspects, such as clinical picture, level of physical fitness, and motor skills. A supervised adapted exercise program is useful to personalized PA programs from an early pediatric age.

Surgical approach to oral lichen planus by submucosal autologous fat grafting.

Oral lichen planus is a chronic autoinflammatory mucositis. Oral lesions are predominantly white; they tend to be bilateral while involving the buccal mucosa especially cheek, tongue, gums, lips, and palate. Many topical and systemic agents are currently used with unpredictable results. Fat grafting is characterized by the placement of multiple parcels of purified fat with blunt cannulas; at the beginning, it was introduced to improve facial aesthetics. Recently, it has been translated to other surgical cases such as posttraumatic deformities and craniofacial anomalies and as ancillary reconstructive procedure after tumor resections. The successful results of this procedure encouraged us to use this approach to a clinical case of oral lichen planus refractory to conventional therapy.

International fitness scale (IFIS): association with motor performance in children with obesity.

Background: Overweight and obesity are defined as abnormal or excessive fat accumulation that presents a risk to health; and compared with their normal-weight peers, these individuals tend to have a lower level of self-confidence, and consequently lower physical activity adherence. Due to these self-perceived barriers, the aim of our study was to evaluate the efficacy of an online training program on self-reported physical fitness (SRPF) in children with obesity (OB). Methods: A total of 32 children with OB carried out physical fitness (PF) tests and were asked to complete the International Fitness Enjoyment Scale (IFIS) questionnaire. The physical fitness tests were the Standing Broad Jump (SBJ), the 6-Min Walking Test (6MWT) and the 4 × 10 m sprint test. Children participated in a 3-weekly 60-min training session through Zoom platform. Before the beginning of the training protocol, OB children were compared with normal weight (NW) ones for PF batteries and the IFIS questionnaire. Changes in performances after the training were assessed by paired Student t and Wilcoxon tests. Results: After the online training program children increased their performance in 6MWT (mean difference (MD) = 54.93; p < 0.0001) in SBJ (MD = 10.00; p = 0.0001) and in 4 × 10 m sprint test (MD = -0.78; p < 0.0001). No differences were found in children's physical fitness perception. Discussion: Our study highlighted how a structured online training program can lead to improvements in PF of children with OB. Instead, the lack of differences in SRPF after the training suggests interesting questions to be explored on the aspects linked to self-perception. Therefore, even if our training protocol could not directly improve SRPF in children with obesity, the enhancement of their PF could be a starting point for achieving this result with a longer training period and consequently improve PA participation for children with OB.

Unraveling Barriers to a Healthy Lifestyle: Understanding Barriers to Diet and Physical Activity in Patients with Chronic Non-Communicable Diseases.

Although the important contribution of nutrition and physical activity to people's health is known, it is equally well known that there are many barriers to adherence to healthy habits (i.e., of an organizational, economic, and/or psychological nature) experienced by the general population, as well as by people with non-communicable diseases. Knowledge of these barriers seems essential to the implementation of the activities and strategies needed to overcome them. Here, we aim to highlight the most frequent barriers to nutrition and exercise improvement that patients with chronic-degenerative diseases experience. Drawing from the Pubmed database, our analysis includes quantitative or mixed descriptive studies published within the last 10 years, involving adult participants with non-communicable diseases. Barriers of an organizational nature, as well as those of an environmental, economic, or psychological nature, are reported. The study of patients' barriers enables healthcare and non-health professionals, stakeholders, and policymakers to propose truly effective solutions that can help both the general population and those with chronic pathologies to adhere to a healthy lifestyle.

Pneumatic Compression Combined with Standard Treatment after Total Hip Arthroplasty and Its Effects on Edema of the Operated Limb and on Physical Outcomes: A Pilot Clinical Randomized Controlled Study.

Total hip arthroplasty (THA) is one of the most successful orthopedic procedures and is highly effective at improving function and quality of life. However, patients commonly experience edema immediately after hospitalization and also after discharge, which can lead to health consequences and a lower quality of life. For these reasons, the aim of this study (NCT05312060) was to evaluate the effectiveness of a specific intermittent leg pneumatic compression on lower limb edema and physical outcomes in patients after total hip arthroplasty, compared to standard conservative treatment. A total of 47 patients were enrolled and randomly allocated into two groups: the pneumatic compression group (PG = 24) and the control group (CG = 23). The CG performed the standard venous thromboembolism therapy, which included pharmacological prophylaxis, compressive stockings, and electrostimulation, while the PG combined pneumatic compression with standard VTE therapy. We evaluated thigh and calf circumferences, knee and ankle ranges of motion, pain, and walking autonomy. Our results showed a greater reduction in thigh and calf circumferences for PG (p < 0.001), while other outcomes were similar for the two groups (p > 0.05). The combination of standard therapy with pneumatic leg compression was more effective at reducing lower limb edema and thigh and calf circumferences than standard treatment. Our results suggest that pressotherapy treatment is a valuable and efficient option for managing lower limb edema after THA.

Piezoelectric ultrasonic debridement as new tool for biofilm removal from orthopedic implants: A study in vitro.

Pulse lavage (PL) debridement is the standard treatment used in Debridement, Antibiotics and Implant Retention (DAIR) for bacterial biofilm removal during acute and early postoperative cases of periprosthetic joint infection (PJI). The failure rate of DAIR is still high due to the inadequacy of PL in removing the biofilm. Ultrasound-based techniques are a well-established tool for PJI diagnosis due to their ability to completely eradicate the biofilm from implant surfaces. Hence, this study investigates the efficiency of a piezoelectric ultrasonic scalpel (PUS) in removing bacterial biofilm from different orthopedic implant materials in vitro and compares the results with PL. Biofilms of methicillin-resistant Staphylococcus aureus strains were grown on titanium alloy (Ti6Al4V ELI), stainless steel (AISI 316L), and ultrahigh molecular weight polyethylene (UHMWPE) disks for 24 h. The disks of each material were divided into three groups: (i) a control group (no lavage/debridement), (ii) a group treated with PL, (iii) a group treated with PUS. The disks were then sonicated for viable cell count to measure the residual biofilm content. Compared to the initial cell count (105 CFU/mL for each material), PL showed a two-log reduction of CFU/mL (p < 0.001 for each material), while for PUS a four-log reduction was found (p < 0.001 for each material). The comparison between the two lavage/debridement displayed a two-log reduction of CFU/mL (p < 0.001 for each material) of PUS compared with PL. Its increased efficiency compared with PL promotes the use of PUS in removing bacterial biofilm from orthopedic implants, suggesting its implementation to improve the success rate of DAIR.

Physical fitness trend after COVID-19 restrictions in Italian school-aged children: a cross-sectional study.

BACKGROUND: Physical fitness (PF) is a marker of health in children. Muscular strength and speed-agility PF components play a crucial role in musculoskeletal development and bone health. The outbreaks of COVID-19 pandemic changed the daily and sports activities in younger increasing sedentary habits with a detrimental effect on PF. We aimed to investigate the impact of COVID-19 restrictions on PF in Italian school-aged children. METHODS: We recruited 286 elementary school children, and they were tested through an internationally validated battery test, which evaluate muscular strength and speed-agility (as a multifactorial performance) prior (2018) and after the outbreak of COVID-19 pandemic (2021). RESULTS: Our results showed a reduction in the lower limb strength (SBJ in boys mean difference (MD) -0.42 m; SBJ in girls MD=-0.20 m; P<0.05) and in the speed-agility ability (10x5 m in boys MD=14.1 s; 10x5 m in girls MD=11.2 s; P<0.05), while the upper limb strength remained steady before and after the restrictions. Specifically, for boys of all ages there was a reduction in lower limb strength and in speed-agility but not in upper limb strength. For girls of all ages there was not a recurrent trend, while for 6-8 girls there was a reduction only speed-agility, for 9-11 girls there was a reduction in lower limb and speed-agility. CONCLUSIONS: Our results could be useful to help teachers and sport specialists to evaluate and improve strength and speed-agility in children. We encourage trainers and sport specialists to implement programs to help children to become more active and healthier during their lifespan.

Benefits in Cardiac Function from a Remote Exercise Program in Children with Obesity.

Physical activity (PA) is a crucial factor in preventing and treating obesity and related complications. In this one-arm pre−post longitudinal prospective study, we evaluated the effects of a 12-week online supervised training program on cardiac morphology, function and blood pressure (BP) in children with obesity. The training program consisted of three sessions per week, each lasting 60 min. Advanced echocardiographic imaging (tissue Doppler and longitudinal strain analysis) was used to detect subclinical changes in heart function. Categorical variables were described as counts and percentages; quantitative variables as the mean and standard deviation (SD) as they were normally distributed (Shapiro−Wilks test). Pre−post comparisons were made with a paired t-test. A total of 27/38 (71%) enrolled patients (18M/9F, 11 ± 2 years) completed the training protocol and were considered in the analysis. At baseline, no hypertensive patient was noted; all echocardiographic variables were within the normal range. After training, we observed a significant reduction in BP parameters, including systolic BP values and Z-score, diastolic BP values, centiles and Z-score, and mean arterial pressure (all p < 0.05). Significant variations in echocardiographic interventricular septum (IVSd) thickness (p = 0.011), IVSd Z-score (p = 0.001), left ventricular (LV) end-diastolic diameter (p = 0.045), LV posterior wall thickness Z-score (p = 0.017), and LV global longitudinal strain (p = 0.016) were detected. No differences in LV diastolic function and right ventricular strain were noted. PA plays a decisive role in improving BP control and has benefits on left ventricle systolic function, representing a strategic approach to limit CV risk. Online exercise could be an excellent method of training in children with obesity.

Exergames to Limit Weight Gain and to Fight Sedentarism in Children and Adolescents with Obesity.

Exergames are defined as digital games that require bodily movements to play, stimulating an active gaming experience to function as a form of physical activity (PA). The players interact with the game through whole-body movements improving energy expenditure. Exergames may be effective in improving physical and psychological aspects of children and adolescents with obesity. In this narrative review, we synthesized the current evidence regarding the role of exergames in modifying body composition and weight and in promoting changes in sedentary behavior to define the benefits of active video games as useful tools for fighting sedentarism and to outline the future directions of exergaming as a supplementation exercise rather than a replacement in educational programs for pediatric obesity. Data from the literature indicate that exergames may offer an interesting impact on childhood obesity and may be considered a potential strategy for controlling weight gain and body composition, promote PA, and decrease time spent on sedentary behavior in children and adolescents with obesity. However, exergame use also has some limits, such as children's poor self-regulation and poor structuring of exergame use. Therefore, a prudent approach should be maintained, and additional high-quality research is needed to determine if exergames can be effectively used in the treatment of childhood obesity and if new digital media, as a supplementation of exercise rather than a replacement, could be considered to combat sedentary behavior in educational programs for pediatric obesity prevention.