Consensus paper on postural dysfunction: recommendations for prevention, diagnosis and therapy.

Good fundamentals of posture and balance are essential for the efficient performance of both simple daily tasks and more complex movement patterns. In particular, postural balance is the ability to keep the body in equilibrium and to regain balance after the shift of body segments: postural control mechanisms of integration of the visual, vestibular and foot afferential channels contribute to this. This document provides recommendations based on scientific evidence, clinical practice, and consensus between experts concerning the prevention, diagnosis, and treatment of postural dysfunction at the three stages of life as the developmental age, adult age, and old age > 65 years and follows the "National Guidelines on Classification and Measuring of Posture and its Dysfunctions" per the Italian Ministry of Health (December 2017). The paper answers four main questions: i) "Which measures can be adopted to prevent postural dysfunctions?" ii) "What can we do in order to make a correct diagnosis of postural dysfunction?" iii) "What are the correct treatment programs for postural dysfunctions?" iv) Which professional competencies and experiences are useful for preventing, diagnosing and treating postural dysfunctions? By the Consensus of the Experts and the scientific evidence, emerge that the approach to postural dysfunctions requires a multidisciplinary and interdisciplinary team. Furthermore, rehabilitation treatment interventions must be specific to the age groups that have been indicated, to consider the integration of the main systems and subsystems of postural control that change with age.

Methods and procedures in adipose stem cells: state of the art and perspective for translation medicine.

Stem cells have potential in the retrieval and repair of injured tissue and renovation of organ function. To date, several studies have been carried out to elucidate how differentiation of stem cells can be used in regenerative medicine applications. Adipose tissue is an abundant and accessible source of stem cell, useful for regenerative therapeutic use. Adipose stem cells (ASCs) are favorable for future translational research and can be applied in many clinical settings. Adipose tissue repair has been recently adopted in clinical trials to prove that ASCs can be successfully used in patients. Variability in cell culture procedures (isolation, characterization, and differentiation) may have an influence on the experimental outcome. In this report, we consider the selection mechanisms of ASCs using flow cytometry, cell culture, freezing/thawing, cell cycle evaluation, histochemistry/immunofluorescence, and differentiation of ASCs. Both researchers and regulatory institutions should consider a new policy for GMP procedures and protocols, paying special attention to stem cell bio-physiology, to facilitate more clinically oriented studies. ASCs show angiogenic properties, with prospects of repairing tissue damaged by radiotherapy, as well as possessing the ability to heal chronic wounds. They can also be useful in surgical practice. We focus on the potential clinical application of ASCs that are currently available regarding translational medicine and the methods and procedures for their isolation, differentiation, and characterization.

The value of multifocal electroretinography to predict progressive visual acuity loss in early AMD.

BACKGROUND: To investigate, in a prospective study, the role of multifocal electroretinography (mfERG) for predicting visual acuity decline in early age-related macular degeneration (AMD) with time. METHODS: Twenty-six early AMD patients (12 males and 14 females, mean age 66.9 ± 9.8; range 46-82 years) were included in the study. A complete ophthalmic examination and mfERG (Retiscan, Roland Germany, ISCEV standard protocol) were performed at the study entry (baseline), after 20 and 24 months. The first-order kernel mfERG responses were analyzed by ring analysis. The amplitude density (AD) of the first positive peak (P1, nV/deg(2)), the P1 amplitude (µV) and P1 implicit time (ms) for Rings 1 (central) to 6 (most peripheral) were evaluated. Data were statistically analyzed by analysis of variance and receiver operating characteristic (ROC) curves. RESULTS: The loss in the mfERG Ring 1 AD from normal control values, recorded at baseline, was correlated with the decrease in ETDRS visual acuity with time (P = 0.004). ROC analysis showed that, after 24 months, the average decline in visual acuity was greater (3 letters vs 0.4 letters, P = 0.0021) in patients whose Ring 1 P1 AD at baseline was equal to or less than 65.9 nV/deg(2), compared to those with higher AD values. Both P1 amplitude and AD of Ring 1 had an area under the curve of 0.702 (95% confidence interval 0.50-0.92) with a sensitivity of 64.3% (35.14-87.24%) and a specificity of 91.7% (61.52-99.79%). CONCLUSIONS: The present results indicate that mfERG P1 amplitude and AD of Ring 1 may be highly specific to predict visual acuity decline in early AMD.

The Italian registry of cystic echinococcosis (RIEC): the first prospective registry with a European future.

Cystic echinococcosis (CE), a worldwide zoonosis, is highly endemic in southern and eastern Europe. Its actual prevalence is unknown due to the lack of efficient reporting systems designed to take into account the particular features of the disease. Neglect of CE makes diagnosis and clinical management difficult outside referral centres, with inconsistencies in clinical practice and often unnecessary procedures carried out that have associated risks and costs. The Italian registry of CE (RIEC) is a prospective multicentre registry of CE patients seen from January 2012 in Italian health centres; data are voluntarily submitted to the registry. Its aims are to show the prevalence of CE in Italy, bring the importance of this infection to the attention of health authorities, encourage public health policies towards its control, and stimulate biological, epidemiological and clinical research on CE. From January 2012 to February 2014, a total 346 patients were enrolled in 11 centres, outnumbering national reports of many CE-endemic European countries. We discuss preliminary data and challenges of the RIEC, template for the European registry of CE, which has been implemented within the Seventh Framework Programme project HERACLES (Human cystic Echinococcosis ReseArch in CentraL and Eastern Societies) since September 2014.

Paraplegia in a patient with Von Hippel Lindau syndrome: surgical and reconstructive treatment of Marjolin's ulcer. A case report.

STUDY DESIGN: Marjolin's ulcer is a squamous cell carcinoma that develops in posttraumatic scars and chronic wounds. Suspicion of such lesions should be raised in chronic wounds demonstrating characteristic changes. We have reported the peculiar phenomenon of malignant transformation of chronic pressure sores that occurred in a paraplegic patient. OBJECTIVES: The aim of this study was to cover the extensive defects by a last resort reconstructive option. SETTING: Department of Plastic and Reconstructive Surgery, Università Politecnica delle Marche, Ancona, Italy. METHODS AND RESULTS: A 40-year-old paraplegic man, with multiple hemangioblastomas of the brain and spinal cord due to Von Hippel Lindau syndrome developed pressure ulcers with unstable healing over the sacral, trochanteric, bilateral, and ischiatic areas after 15 years from neurosurgery. The biopsy result showed an invasive squamous carcinoma. Carcinomas in pressure sores are highly aggressive, and they need to be treated more radically. In our case we opted for a demolitive surgical treatment including musculocutaneous rotational flap harvested from total left thigh to cover the extensive defects. The limb was previously disarticulated. CONCLUSION: In Marjolin's ulcer, multiple biopsies are the first-line modality for the early diagnosis as they are a safe method with high rate of accuracy. First-line treatment is surgery consisting of radical excision with lymph node dissection, if they are involved. Adjuvant radiation therapy may be used in selected patients. Management of massive pelvic defects can be a challenging problem. The pedicled lower limb flap offers a technique that can be considered as a last resort procedure for extensive defects where other options are insufficient or not available anymore. In our case the patient is disease-free after 2 years of follow-up.

Study of a Subcutaneous Lesion of the Shoulder: The Saint Paolino Tumor.

In certain small counties in southern Italy, traditional Catholic festivals are observed by erecting tall, large, and weighty wagons referred to as "lilies." These wagons are borne on the shoulders of several individuals known as "cradles." This practice has given rise to the emergence of a distinct subcutaneous neoformation on the shoulder. This study investigates the unique clinical and anatomopathological attributes of "Saint Paolino tumor" (named in honor of the Catholic patron of the widely celebrated lilies festival). This tumor presents as a posttraumatic intermittent chronic lesion occurring on the shoulder, necessitating differential diagnosis from other cutaneous and soft tissue lesions such as spontaneous lipomas, elastofibroma, Madelung disease, and liposarcoma.

Surgical approach to a rare case of Beckwith Wiedemann syndrome with left thigh hyperplasia.

Thigh lift surgery is generally performed in patients with severe weight loss outcomes, particularly those undergoing bariatric surgery. However, there are other congenital malformation conditions that may require the same treatment, such as Beckwith Wideman syndrome.

Human responses against HER-2-positive cancer cells in human immune system-engrafted mice.

BACKGROUND: Human immune system (HIS)-engrafted mice are new tools to investigate human immune responses. Here, we used HIS mice to study human immune responses against human HER-2-positive cancer cells and their ability to control tumour growth and metastasis. METHODS: BALB/c Rag2(-/-), Il2rg(-/-) mice were engrafted with CD34(+) or CD133(+) human cord blood hematopoietic stem cells (HSC) and vaccinated with human HER-2-positive cancer cells SK-OV-3 combined to human IL-12. RESULTS: Both CD34(+) or CD133(+) human HSC gave long-term engraftment and differentiation, both in peripheral blood and in lymphoid organs, and production of human antibodies. Vaccinated mice produced specific anti-HER-2 human IgG. An s.c. SK-OV-3 challenge was significantly inhibited (but not abolished) in both vaccinated and non-vaccinated HIS mice. Tumours were heavily infiltrated with human and murine cells, mice showed NK cells and production of human interferon-γ, that could contribute to tumour growth inhibition. Vaccinated HIS mice showed significantly inhibited lung metastases when compared with non-vaccinated HIS mice and to non-HIS mice, along with higher levels of tumour-infiltrating human dendritic cells. CONCLUSION: Anti-HER-2 responses were elicited through an adjuvanted allogeneic cancer cell vaccine in HIS mice. Human immune responses elicited in HIS mice effectively inhibited lung metastases.

Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease.

BACKGROUND: Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher's disease, among patients with Parkinson's disease. We aimed to ascertain the frequency of GBA mutations in an ethnically diverse group of patients with Parkinson's disease. METHODS: Sixteen centers participated in our international, collaborative study: five from the Americas, six from Europe, two from Israel, and three from Asia. Each center genotyped a standard DNA panel to permit comparison of the genotyping results across centers. Genotypes and phenotypic data from a total of 5691 patients with Parkinson's disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel-Haenszel procedure used to estimate odds ratios across centers. RESULTS: All 16 centers could detect two GBA mutations, L444P and N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of patients and 3% of controls, and among non-Ashkenazi Jewish subjects, either mutation was found in 3% of patients and less than 1% of controls. GBA was fully sequenced for 1883 non-Ashkenazi Jewish patients, and mutations were identified in 7%, showing that limited mutation screening can miss half the mutant alleles. The odds ratio for any GBA mutation in patients versus controls was 5.43 across centers. As compared with patients who did not carry a GBA mutation, those with a GBA mutation presented earlier with the disease, were more likely to have affected relatives, and were more likely to have atypical clinical manifestations. CONCLUSIONS: Data collected from 16 centers demonstrate that there is a strong association between GBA mutations and Parkinson's disease.

Differential expression of estrogen receptor α and ß transcripts in tissues and in primary culture cells from pubertal gynecomastia.

BACKGROUND: Pubertal gynecomastia is a common problem occurring in up to 65% of adolescent boys. Gynecomastia comes at a time when self-image awareness is at its greatest and psychologically could be a psychologically disabling condition. Surgery is considered the mainstay of treatment for severe or persistent cases. A medical management aimed at altering the effective androgen/estrogen ratio has been suggested with inconstant results. Some promising results have been obtained by using anti-estrogens. Surprisingly there are no data on the estrogen receptor (ER) α and ß RNA expression in gynecomastia. AIM: We studied ER RNA subtypes in pubertal gynecomastia. METHODS: ERα and ß RNA were determined by real time RT-PCR in 50 mammary samples from pubertal boys with idiopathic gynecomastia subjected to reductive mammoplasty. To study ERα and ß pattern of expression, epithelial and stromal primary cell cultures were set up from fresh tissues. RESULTS: These analyses indicated that in all stromal cells ERß was expressed at higher level than ERα and in epithelial cells both ERα and ERß were barely detectable. CONCLUSIONS: Our data suggest that also stromal cells are involved in the pathophysiology of pubertal gynecomastia. The high level of expression of ERß seen in pubertal gynecomastia adds new insight on validation of ERß as a target for candidate diseases and exploration of ERß as a marker for clinical decision-making and treatment in pubertal gynecomastia. This could drive to search for new and selective anti-estrogen drugs for medical treatment of pubertal gynecomastia with a particular attention to the ERß-selective ligand.

Synergistic effects of cryolipolysis and shock waves for noninvasive body contouring.

BACKGROUND: Excess body fat, localized adiposity, and cellulite represent important social problems. To date, techniques using radiofrequencies, cavitation and noncavitation ultrasound, and carbon dioxide have been studied as treatments for noninvasive body contouring. Ice-Shock Lipolysis is a new noninvasive procedure for reducing subcutaneous fat volume and fibrous cellulite in areas that normally would be treated by liposuction. It uses a combination of acoustic waves and cryolipolysis. Shock waves, used normally in the treatment of renal calculi and musculoskeletal disorders, are focused on the collagen structure of cellulite-afflicted skin. When used on the skin and underlying fat, they cause a remodeling of the collagen fibers, improving the orange-peel appearance typical of the condition. Cryolipolysis, on the other hand, is a noninvasive method used for the localized destruction of subcutaneous adipocytes, with no effects on lipid or liver marker levels in the bloodstream. The combination of the two procedures causes the programmed death and slow resorption of destroyed adipocytes. METHODS: In this study, 50 patients with localized fat and cellulite were treated with a selective protocol for the simultaneous use of two transducers: a Freezing Probe for localized fatty tissue and a Shock Probe for fibrous cellulite. RESULTS: The procedure significantly reduced the circumference in the treated areas, significantly diminishing fat thickness. The mean reduction in fat thickness after treatments was 3.02 cm. Circumference was reduced by a mean of 4.45 cm. Weight was unchanged during the treatment, and no adverse effects were observed. Histologic and immunohistochemical analysis confirmed a gradual reduction of fat tissue by programmed cell death. Moreover, the reduction in fat thickness was accompanied by a significant improvement in microcirculation, and thus, the cellulite. The safety of the method also has been highlighted because it is accompanied by no significant increase in serum liver enzymes or serum lipids. CONCLUSION: The study aimed to observe the effects of the new technique in the treatment of localized fat associated with cellulite in order to assess adipose tissue alterations, cellular apoptosis, and levels of serum lipid or liver markers. The findings show that the action of Ice-Shock Lipolysis is a safe, effective, and well-tolerated noninvasive procedure for body contouring. In particular, the authors believe that this could be an ideal alternative to liposuction for patients who require only small or moderate amounts of adipose tissue and cellulite removal or are not suitable candidates for surgical approaches to body contouring.

Alar cinch sutures in orthognathic surgery: scoping review and proposal of a classification.

Orthognathic surgery and the Le Fort I osteotomy result in noticeable alterations to the nasal/nasolabial anatomy. The alar base cinch technique is a surgical technique to control lateralization of the base of the nose and is well described in the literature. The aim of this scoping review was to identify every unique alar cinch suture technique reported in orthognathic surgery and to propose a classification for the different techniques described. A search was conducted in the PubMed, Cochrane Library, and Scopus electronic databases covering the period May 1980 to July 2020, which identified 10 articles that were eligible for this review. Among these, there were several proposals for modifications to the technique, and different studies to show the effectiveness of one type among all others. Despite observing multiple techniques and variations of these while performing this review, the lack of a classification for alar cinch suture was noticed. Therefore, we propose a classification of the alar cinch suture that includes four types, which cover all of the cinching techniques described. It is believed that the use of a standardized classification may be useful to avoid duplicate publishing of techniques and to set a standard for further studies.

Few Italian drug users undergo HIV testing.

We estimated the proportion of drug users at treatment centres in Italy who had undergone HIV testing and the correlates of testing. Of the 1,917 drug injectors, 37.4% had been tested in the current year; of the 665 non-injectors, 28% had been tested. Among injectors, testing was associated with: being older than 35, foreign nationality, residing in central Italy, drug use for over 2 years, and having undergone both pharmacological and psychological treatment. Among non-injectors, an association was found for foreign nationality and not having been treated at other facilities. The results stress the need to facilitate access to testing.

Combined allogeneic tumor cell vaccination and systemic interleukin 12 prevents mammary carcinogenesis in HER-2/neu transgenic mice.

Transgenic Balb/c mice expressing the transforming rat HER-2/neu oncogene develop early and multifocal mammary carcinomas. Within the first 5 months of life the tissue-specific expression of HER-2/neu causes a progression in all their 10 mammary glands from atypical hyperplasia to invasive carcinoma. It was previously observed that chronic administration of interleukin (IL)-12 increased tumor latency, but every mouse eventually succumbed to multiple carcinomas. A significant improvement in tumor prevention was sought by administering allogeneic mammary carcinoma cells expressing HER-2/neu combined with systemic IL-12. This treatment reduced tumor incidence by 90% and more than doubled mouse lifetime. For the maximum prevention p185(neu) antigen must be expressed by allogeneic cells. IL-12 treatment strongly increased the cell vaccine efficacy. The mammary glands of mice receiving the combined treatment displayed a markedly reduced epithelial cell proliferation, angiogenesis, and HER-2/neu expression, while the few hyperplastic foci were heavily infiltrated by granulocytes, macrophages, and CD8(+) lymphocytes. Specific anti-HER-2/neu antibodies were produced and a nonpolarized activation of CD4(+) and CD8(+) cells secreting IL-4 and interferon (IFN)-gamma were evident. A central role for IFN-gamma in the preventive effect was proven by the lack of efficacy of vaccination in IFN-gamma gene knockout HER-2/neu transgenic Balb/c mice. A possible requirement for IFN-gamma is related to its effect on antibody production, in particular on IgG2a and IgG2b subclasses, that were not induced in IFN-gamma knockout HER-2/neu mice. In conclusion, our data show that an allogeneic HER-2/neu-expressing cell vaccine combined with IL-12 systemic treatment can prevent the onset of genetically determined tumors.

Interleukin 12-mediated prevention of spontaneous mammary adenocarcinomas in two lines of Her-2/neu transgenic mice.

The ability of interleukin (IL)-12 to prevent tumors when administered to individuals with a genetic risk of cancer was studied in two lines of transgenic mice expressing rat HER-2/neu oncogene in the mammary gland. Female BALB/c (H-2(d)) mice carrying the activated HER-2/ neu oncogene show no morphological abnormalities of the mammary gland until 3 wk of age. They then progress through atypical hyperplasia to in situ lobular carcinoma and at 33 wk of age all 10 mammary glands display invasive carcinomas. Adult FVB mice (H-2(q)) carrying the HER-2/neu protooncogene develop mammary carcinomas with a longer latency (38-49 wk) and a lower multiplicity (mean of 2.6 tumors/mice). Treatment with IL-12 (5 daily intraperitoneal injections, 1 wk on, 3 wk off; the first course with 50 ng IL-12/day, the second with 100 ng IL-12/day) begun at 2 wk of age in BALB/c mice and at 21 wk of age in FVB mice markedly delayed tumor onset and reduced tumor multiplicity. Analogous results were obtained in immunocompetent and permanently CD8(+) T lymphocyte-depleted mice. In both transgenic lines, tumor inhibition was associated with mammary infiltration of reactive cells, production of cytokines and inducible nitric oxide synthase, and reduction in microvessel number, in combination with a high degree of hemorrhagic necrosis.

DJ-1 is a Parkinson's disease susceptibility gene in southern Italy.

Mutations in the gene DJ-1 have been shown to be a rare cause of early-onset Parkinson's disease (EOPD). Since DJ-1 mutations have been found in patients with Parkinson's disease (PD) from southern Italy, we aimed to investigate whether polymorphisms within the DJ-1 gene could represent a risk factor for sporadic PD. First, we genotyped 294 patients with PD and 298 controls coming from southern Italy to assess the distribution of the insertion/deletion (Ins/Del) polymorphism. In a second phase, we identified five single-nucleotide polymorphisms (SNPs) useful to delimit a region potentially involved and genotyped all patients and controls for these markers. All the markers analyzed were significantly associated with PD at both allelic and genotypic level. The most significant association with the disease was found at the Ins/Del polymorphism (p = 0.0001; adjusted odds ratio (OR ) = 2.05; confidence interval (CI ) = 1.36-3.08). When we considered a three-marker sliding window, we found a highly significant association between the disease and the haplotypes including markers rs17523802, Ins/Del, and rs3766606 (p = 0.0007) and markers Ins/Del, rs3766606 and rs7517357 (p = 0.0054). Our results indicate that polymorphisms located in a region spanning 3535 bp from the promoter to the intron 2 of the DJ-1 gene confer risk to sporadic PD in southern Italy.

In vitro activity of cefditoren versus other antibiotics against S. pneumoniae clinical strains isolated in Italy.

Over the last twenty years there has been an alarming increase in isolation of Streptococcus pneumoniae strains with a reduced susceptibility not only to penicillin, but also to other betalactams and macrolides. This phenomenon justifies the great interest in new antibiotics. Cefditoren, a new aminothiazolyl oral cephalosporin, recently commercialized in Italy, is characterized by an extended activity against penicillin-resistant S. pneumoniae. The aim of this study is to evaluate the incidence of the resistance/susceptibility to various antibiotics in 1000 strains of S. pneumoniae (678 SPSS, 219 SPPI and 103 SPPR), clinically isolated during 2009. The data obtained by our in vitro study show that cefditoren is the most active agent against S. pneumoniae. In fact, the MIC90 values of 0.5 micrograms/ml obtained could be particularly significant in therms of therapeutic predictivity.

Cefiderocol for Extensively Drug-Resistant Gram-Negative Bacterial Infections: Real-world Experience From a Case Series and Review of the Literature.

Cefiderocol is a new siderophore cephalosporin with activity against carbapenem-resistant gram-negative bacteria. Data on its clinical efficacy are limited to complicated urinary tract infections. We present a series of 3 patients successfully treated with cefiderocol for complicated health care-associated infections and review published case reports.

Experimental results and related clinical implications of PET detection of epidermal growth factor receptor (EGFr) in cancer.

The epidermal growth factor receptor (EGFr) is one of the most studied molecules as a target for cancer therapy. Over these last few years, several studies attempting to identify predictive biomarkers of treatment response, such as the receptor status or other molecules related to the downstream signalling pathway, have been conducted. However, from a clinical point of view, the information obtained from ex vivo analyses still has various limitations that may be overcome by the combination with molecular imaging technologies which may provide a noninvasive, global, in vivo evaluation of the molecular tumour background. The aim of this review is to report the preclinical results of all positron emission tomography (PET) tracers synthesized until now for in vivo detection of EGFr in cancer. Two classes of PET compounds have been developed: labelled small molecules such as tyrosine kinase inhibitors and labelled monoclonal antibodies. The in vitro and in vivo results of these PET tracers are very different depending on the chemical properties, positron emission radionuclide, or animal models. As a consequence, various critical questions are still open, and the implications of a translation in the clinical setting for EGFr imaging in cancer patients is discussed.