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Idiopathic non-histaminergic acquired angioedema (InH-AAE) is a rare disease, with unknown etiology and pathogenesis, characterized by recurrent clinical manifestations and resistance to antihistamines and corticosteroids. We aim to evaluate clinical features and potential markers of disease in an Italian cohort of patients with InH-AAE. We enrolled 26 patients diagnosed with InH-AAE. Information about clinical features, treatments, routine laboratory investigations, immunological and genetic tests were collected. We assessed plasma levels of complement components, angiogenic and lymphangiogenic mediators, proinflammatory cytokines and chemokines, and activity of phospholipases A2. Finally, patients underwent nailfold videocapillaroscopy (NVC); both quantitative and qualitative capillaroscopic parameters were analyzed. Plasma levels of VEGFs were similar in healthy controls and in InH-AAE patients. ANGPT1 was decreased in InH-AAE patients compared to controls while ANGPT2 was similar to controls. Interestingly, the ANGPT2/ANGPT1 ratio (an index of vascular permeability) was increased in InH-AAE patients compared to controls. sPLA2 activity, elevated in patients with C1-INH-HAE, showed differences also when measured in InH-AAE patients. TNF-α concentration was higher in InH-AAE patients than in healthy controls, conversely, the levels of CXCL8, and IL-6 were similar in both groups. At the NVC, the capillary loops mainly appeared short and tortuous in InH-AAE patients. InH-AAE represents a diagnostic challenge. Due to the potential life-threatening character of this condition, a prompt identification of the potentially bradykinin-mediated forms is crucial. A better comprehension of the mechanism involved in InH-AAE would also lead to the development of new therapeutic approaches to improve life quality of patients affected by this disabling disease., Competing Interests: Declarations Competing interests The authors declare no competing interests. Conflict of interest None., (© 2024. The Author(s).)

Background: Survivors of severe COVID-19 related respiratory failure may experience durable functional impairments. We aimed at investigating health-related quality of life (HR-QoL), physical functioning, fatigue, and cognitive outcomes in COVID-19 patients who received invasive mechanical ventilation (IMV)., Methods: Case-series, prospective, observational cohort study at 18 months from hospital discharge. Patients referring to the Intensive Care Unit (ICU) of Humanitas Research Hospital (Milan, Italy) were recruited if they needed IMV due to COVID-19 related respiratory failure. After 18 months, these patients underwent the 6-min walking test (6MWT), the Italian version of the 5-level EQ-5D questionnaire (EQ-5D-5L), the Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire (FACIT-F), the Trail Making Test-B (TMT-B) and the Montreal Cognitive Assessment-BLIND test (MoCA-BLIND)., Results: 105 patients were studied. The population's age was 60 ± 10 years on average, with a median Frailty Scale of 2 (Hodgson et al., 2017; Carenzo et al., 2021a [2,3]). EQ-VAS was 80 [70-90] out of 100, walked distance was 406 [331-465] meters, corresponding to about 74 ± 19,1% of the predicted value. FACIT-F score was 43 [36-49] out of 52, and MoCa-BLIND score was 19 (DeSalvo et al., 2006; von Elm et al., 2008; Herdman et al., 2011; Scalone et al., 2015 [16-20]) out of 22. The median TMT-B time was 90 [62-120] seconds. We found a possible age and gender specific effect on HR-QoL and fatigue., Conclusions: After 18 months from ICU discharge, survivors of severe COVID-19 respiratory failure experience a moderate reduction in HR-QoL, and a severe reduction in physical functioning. Fatigue prevalence is higher in younger patients and in females. Finally, cognitive impairment was present at a low frequency., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: To translate and cross-culturally adapt the Consultation and Relational Empathy (CARE) measure into Italian, examine its internal reliability, and construct validity in a rehabilitation setting., Materials and Methods: The translation process consisted of two forward translations, a pre-final version, a back-translation, and a final version, in accordance with available guidelines. We administered the Italian version of the CARE measure to 101 patients hospitalised for rehabilitation after total hip or total knee arthroplasty (THA and TKA). We assessed face validity, internal reliability, and construct validity., Results: Face validity was high. Patients answered all questions and the "does not apply" option was never selected. Internal reliability (Cronbach's α = 0.962) resulted in line with the original version. The exploratory factor analysis confirmed the unidimensional structure of the CARE measure with 74.82% of variance explained by the first factor., Conclusions: The Italian version of the CARE measure showed high face validity. Internal reliability and construct validity were in line with the original version in patients undergoing rehabilitation after THA and TKA.IMPLICATIONS FOR REHABILITATIONInternal reliability and construct validity of the Italian version of the CARE measure are in line with those of the original version of the CARE measure.The Italian CARE measure can be used to assess patient's perceived therapist's empathy in patients undergoing physical therapy after THA and TKA.Physiotherapists should use the CARE measure with more caution in other rehabilitative contexts.

Background: Robot-based treatments are developing in neurorehabilitation settings. Recently, the Italian National Health Systems recognized robot-based rehabilitation as a refundable service. Thus, the Italian neurorehabilitation community promoted a national consensus on this topic., Objective: To conceptualize undisclosed perspectives for research and applications of robotics for neurorehabilitation, based on a qualitative synthesis of reference theoretical models., Methods: A scoping review was carried out based on a specific question from the consensus Jury. A foreground search strategy was developed on theoretical models (context) of robot-based rehabilitation (exposure), in neurological patients (population). PubMed and EMBASE® databases were searched and studies on theoretical models of motor control, neurobiology of recovery, human-robot interaction and economic sustainability were included, while experimental studies not aimed to investigate theoretical frameworks, or considering prosthetics, were excluded., Results: Overall, 3699 records were screened and finally 9 papers included according to inclusion and exclusion criteria. According to the population investigated, structured information on theoretical models and indications for future research was summarized in a synoptic table., Conclusion: The main indication from the Italian consensus on robotics in neurorehabilitation is the priority to design research studies aimed to investigate the role of robotic and electromechanical devices in promoting neuroplasticity.

Purpose: To date in Italy we do not have sufficient information on the rehabilitation process of older patients with hip fractures especially in the context of dementia. The main aims of the study were to gather information on the characteristics of older patients with hip fracture admitted to rehabilitation units with a specific focus on geriatric syndromes and the rehabilitation process., Methods: A national multi-center "point prevalence study" was conducted in Italy over two index days in 2017 and 2018. All patients aged 70 years and older hospitalized on the index day in Rehabilitation Units after a hip fracture were eligible., Results: A total of 615 patients were included. Most of the hospitals involved were from northern Italy, to a lesser extent from central and from southern Italy. The mean age was 83.08 ± 7.9 years. Almost half of the patients lived alone before the hip fracture. Most of the falls happened at home and while walking. The prevalence of delirium, dementia and malnutrition was 9.1%, 36.6%, and 19.3%, respectively. Antidepressants were prescribed in 27% of the population. The multidisciplinary team was activated as follows: occupational therapist in 18.9% of the cases, psychologists in 14.5%, social workers in 15.3%, and speech therapists in 6.5%., Conclusion: The study allowed the collection of data on a relatively large sample of older patients with hip fracture showing the possible current limitations in the correct management of geriatric syndromes in this frail population. Future multicenter longitudinal studies are required to further study this population.

The aim of this study is to assess social, personality and behaviors of alcoholics using Virtual Reality (VR). Specifically, we defined a VR protocol using the free NeuroVR software -- (http://www.neurovr.org) -- to investigate the following factors: drinking behaviors, intrapersonal factors (Emotional Management and Self Esteem) and environmental factors (Relational Competences and Social Pressure). In this preliminary study we evaluated the difference between assessment methods by comparing the VR assessment protocol with the SCID - Structured Clinical Interview for DSM-IV Axis I Disorders - in a sample of 20 alcohol-dependent individuals (10 experimental group + 10 control group) entering a non-pharmacological outpatient treatment. The data, obtained using both qualitative and quantitative analyses, confirm the possibility of using the VR protocol in the assessment of alcohol-dependent patients: the therapist obtains more critical data about behaviors and attitudes in less time. Further, the VR group reported a significant improvement in the motivation for change after the assessment protocol, not found in the SCID group: apparently, the experiential approach required by VR makes the patient more active and involved in the processes of introspection and change. A wider sample and a multicentric trial are now needed to confirm these results.

Unlabelled: We studied the genotype/phenotype correlation in a cohort of glycogen storage disease type (GSD) 1b patients. A total of 25 GSD1b patients, 13 females and 12 males, age range: 4.3-28.4 years, mean:14.6+/-6.8 years; median: 15 years, representing the entire case load of Italian GSD1b patients, were enrolled in the study. Molecular analysis of the glucose 6-phosphate translocase (G6PT1) gene was performed in all patients. We analysed the presence of a correlation among both the clinical features associated with GSD1b (neutropenia, frequency of admission to the hospital for severe infections) and the presence of systemic complications (liver adenomas, nephropathy, bone mineral density defect, polycystic ovaries, short stature, inflammatory bowel disease) and the mutations detected in each patient. Nine patients were homozygous or compound heterozygous for mutations causing stop codons. In particular, three patients were homozygous for the same mutation (400X); of these patients, one showed chronic neutropenia with severe and frequent infections and severe inflammatory bowel disease, another patient cyclic neutropenia associated with rare bacterial infections and mild bowel involvement and the last one normal neutrophil count. Two patients were homozygous for the mutation 128X; one of these patients did not show neutropenia, whereas the other one had severe neutropenia needing frequent hospital admission and was under granulocyte-colony stimulating factor treatment. In three patients no mutations were detected., Conclusion: No correlation was found between individual mutations and the presence of neutropenia, bacterial infections and systemic complications. These results suggest that different genes and proteins modulate neutrophil differentiation, maturation and apoptosis and thus the severity and frequency of infections. The absence of detectable mutations in three patients could suggest that a second protein plays a role in microsomal phosphate transport.

This research has the aim to evaluate the risk of pesticide dermal exposure for workers in greenhouses. We considered the following crops: tomato, cucumber and strawberry, largely spread in Bracciano lake district. The pesticides monitored were: tetradifon on strawberry: metalaxyl, azoxystrobin and fenarimol on cucumber; acrinathrin, azoxystrobin and chlorpyrifos ethyl on tomato. The dermal exposure was evaluated by Dislodgeable Foliar Residue (DFR) measurements employing transfer coefficients got from literature. For risk evaluation, we have compared the dermal exposures with Acceptable Operator Exposure Levels (AOEL). The re-entry time were obtained intercepting the dose decay curves with AOEL values. The re-entry times result higher than two days in the cases of chlorpyrifos on tomato (re-entry time: 3 days), azoxystrobin on tomato (4 days), and tetradifon on strawberry (8 days). The need of measuring specific transfer coefficients is pointed out.

Reported are the clinical, neuroradiologic, and molecular findings in 18 patients with megalencephalic leukoencephalopathy and subcortical cysts (MLC) syndrome. Marked clinical intrafamilial and interfamilial variability in mutation-proven cases was found. A broad spectrum of pathogenetic mutations (missense, splice site, insertion, and deletions) were identified in the MLC1 gene, enlarging the spectrum of allelic variants without a straightforward genotype-phenotype correlation. Five patients did not harbor mutations in MLC1, supporting the existence of at least one other MLC locus.

Gaucher disease (GD), the most prevalent lysosomal storage disease characterized by a remarkable degree of clinical variability, results from deleterious mutations in the glucocerebrosidase gene (GBA). In this paper we report the molecular characterization of 144 unrelated Italian GD patients with the three types of the disease. The allelic frequencies of Italians are reported and the mutation profile is analyzed. Besides the common N370S, L444P, RecNciI, G202R, IVS2+1G>A, D409H, F213I mutations, the different molecular strategies, used for the mutation detection, identified the rare N107L, R131C, R170C, R170P, N188S, S196P, R285C, R285H, W312C, D399N, A446P, IVS10-1G>A, RecDelta55, total gene deletion, as well as 12 mutant alleles that were exclusively present in the Italian population until now: the previously reported R353G, N370S+S488P mosaicism, IVS8(-11delC)-14T>A), Rec I, Y418C, and the seven novel alleles D127X, P159T, V214X, T231R, L354X, H451R, and G202R+M361I. The wide phenotypic differences observed within the genotypic groups as well as between siblings implicate a significant contribution of other modifying genetic and/or non-genetic factors and claim a comprehensive valuation of the patient including clinical., biochemical and molecular investigations for prognosis, appropriate interventive therapy and reliable genetic counseling., (Copyright 2002 Wiley-Liss, Inc.)

Mucopolysaccharidosis type I (MPS-I orMPS1) is an autosomal recessive condition characterized by a broad range of clinical symptoms. Molecular diagnosis of MPS-I is important for analyzing genotype-phenotype correlation and for selecting patients for innovative therapies. In this study we analyzed 30 Italian MPS-I patients with different phenotypes (20 severe, 6 intermediate, 4 mild) in an attempt to recognize the mutational spectrum in our population and to identify major DNA alterations specific to our country. We identified 93% of mutated alleles (56 out of 60) with the reconstruction of the complete genotype in 26 patients out of 30. Twenty-three different mutations were found, 13 of which are novel while the remaining 10 have been already described. Among the novel mutations we found 5 non conservative missense mutations (A160D, E178K, P183R, G197D, D349Y), one nonsense mutation (C53X), 6 deletions (468-470del3, 486-491del6, 755-759del5, 1251delC, 1839-1867del29, 1902-1903del2), and one splice site mutation (IVS11+5G>A). No common mutation for MPS-I is present in our country. Frequently (40% of the alleles), mutations were found in just one or two patients. However, Q70X, P533R, G51D, and W402X mutations were present in several patients (15%, 13.3%, 13.3%, and 11.6% of the alleles respectively) suggesting a Mediterranean origin of the P533R and G51D mutations. In most cases the patients' genotypes were unique combinations of mutations. The great heterogeneity found in our MPS-I population hampers mutation detection and hinders the genotype-phenotype correlation., (Copyright 2002 Wiley-Liss, Inc.)

The present study reports two Italian brothers affected by severe Salla disease (sialic acid storage disease), a slowly progressive autosomal recessive neurodegenerative disorder prevalent in the Finnish population. Mutations of the SLC17A5 gene, which encodes a protein called sialin, are the primary cause of both Salla disease and infantile sialic acid storage disease (ISSD), a clinically distinct severe disorder. All Finnish patients with Salla disease show a R39C mutation. Both patients showed moderate intellectual disability, spastic ataxic syndrome, hypomyelination and cerebellar atrophy on magnetic resonance imaging (MRI), and lysosomal storage, all typical of Salla disease. Mutation analysis of the SLC17A5 gene in the younger brother revealed no R39C mutation, but a 15-bp deletion in exon 6 on one of the alleles. This mutation is the same described in French-Canadian patients with ISSD. Salla disease must be suspected in patients with unexplained psychomotor retardation associated with ataxia and/or pyramidal symptoms, and MRI findings consistent with cerebral hypomyelination, irrespective of the patient's ethnic origin. A mutation screening based on R39C change does not exclude Salla disease outside Finland. Conversely, mutations found in ISSD can be expected, even in patients showing the Salla phenotype (e.g. symptoms at the milder end of the spectrum).

Mucopolysaccharidosis type II (MPS2, or Hunter syndrome), rare X-linked lysosomal storage disorder, results from deleterious mutations in the iduronate-2-sulfatase (IDS) gene. We report here the mutational analysis of a total of 40 unrelated Italian MPS II patients ranging from mild to severe phenotype. We are able to assign the genotype to 29 of them (72.5%), identifying 22 different mutations, five of which are unpublished (c.533delTT, W12X, N265I, c.1131-1142del, c.1131-1305del). A total of 55.2% of the molecularly characterised patients resulted from missense mutations, 20.7% from nonsense mutations, and another 13.8% of patients from small deletions (<20pb) or splice mutations, whereas 10.3% of the cases carried major structural alterations such as large deletion and rearrangements. The results reported here support the evidence of the mutational heterogeneity of the IDS gene as well as the difficulty to correlate genotype and phenotype in the patients with MPSII. However, the molecular characterisation of the patients is advantageous, making the carrier detection feasible for the females in the family at risk and improving the reliability of prenatal diagnosis techniques. Moreover, it provides a good foundation for therapeutic strategies., (Copyright 2001 Wiley-Liss, Inc.)

Type Ia glycogen storage disease (GSD1a) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). Recent cloning of the G6Pase gene and the subsequent identification of several disease-causing mutations have shown an ethnic molecular heterogeneity. Using SSCP analysis and DNA sequencing, we characterized the G6Pase gene of 53 unrelated Italian patients. The two most common mutations, R83C and Q347X, accounted for 66.9% of the mutant alleles. Eight novel mutations and three rare mutations were identified in 15.7% of disease alleles. These results suggest that a DNA-based method can be used as an initial screening in Italian patients clinically suspected of having GSD1a, avoiding liver biopsy for enzymatic diagnosis. In particular, a noninvasive diagnosis is a suitable method for the Italian subpopulation coming from Sicily, where the R83C mutation is present in 80% of mutant alleles. Molecular carrier detection and prenatal diagnosis can be provided to GSD1a families with identified mutation in the propositus.

A group of 27 Italian patients was screened for alpha-L-iduronidase mucopolysaccharidosis type I mutations. Mutations were found in 18 patients, with 28 alleles identified. The two most common mutations in northern Europeans (W402X and Q70X) accounted for 11% and 13% of the alleles, respectively. The R89Q mutation, uncommon in Europeans, was found only in one patient, accounting for 1 of 54 alleles (1.9%). The other mutations, P533R, A327P and G51D, accounted for 11%, 5.6% and 9.3% of the total alleles, respectively. Interestingly, the high frequency of the P533R mutation seems to be confined to Sicily and is higher than the 3% reported in a British/Australian study.

A molecular analysis of the arylsulphatase A gene was performed on 26 unrelated, Italian, late infantile metachromatic leucodystrophy patients. The frequency of the common disease causing mutations 609A and 2381T was 28.8% and 1.9% respectively. Pseudodeficiency allele frequency in patients was found to be 13.5% and a frequency of 10.1% was found in 89 unaffected normal controls. The frequency of the 609A mutation in Italian late infantile patients is lower than in late infantile patients from northern Europe, suggesting a higher frequency of different sporadic mutations in the Italian population. A cooperative in cis effect in phenotype determination involving arylsulphatase A mutations and the eventual background of the pseudodeficiency allele is proposed.

Mutation screening of the glucocerebrosidase gene by SSCP analysis revealed an abnormal pattern of exon 10 in two unrelated Italian Gaucher patients. Direct sequencing of the mutated samples identified a G6490-->A transition. The same mutation has been described before in a Japanese patient with Gaucher disease type III. The clinical phenotype of our patients was type I in one whose second allele carried the N370S mutation and type II in the other one with a L444P mutation. In this latter the G6490-->A substitution cancels a normal Msp I site, while on the opposite chromosome the T6433-->C mutation (L444P) introduces a new Msp I site. Thus, digestion with Msp I of the amplified exon 10 is a useful method for identifying the two mutations simultaneously.

A metachromatic leukodystrophy (MLD) patient affected with the late infantile form was found to be homozygous for an AT-deletion (2324delAT) in the arylsulfatase A gene. The mutation causes a frameshift at the beginning of exon 8 leading to an early termination codon. The parents and unaffected brother of the patient were heterozygous for the microdeletion. The mutation was not detected in another 31 MLD Italian patients. No aberrant transcript caused by the mutation was revealed by the reverse transcription-polymerase chain reaction method.

The child's discomfort and the cost of overnight hospitalization are clear disadvantages of prolonged esophageal pH monitoring. The aim of this study was to verify the reliability of short recording versus 24-h testing in a pediatric series with symptoms suggestive of gastroesophageal reflux (GER) disease. A 24-h pH monitoring performed on 160 patients with either gastroenterological symptoms (n = 61), respiratory problems (n = 58), or emesis plus respiratory problems (n = 41) was reviewed. Regardless of clinical presentation, children were also classified according to age: < 12 months (n = 39), 12-71 months (n = 81), and 72-168 months (n = 40). A diurnal fraction of 6 h, including at least 2 h after a meal, was compared to the entire 24-h recording in all groups with respect to the reflux index (RI) (sum of the periods with pH < 3.9 expressed as percentage of time) and reflux/h. RIs of > 10% were considered positive in patients < 1 year of age, whereas RIs of > 5% were considered positive in other age groups. Negative predictive values of the short recording RI ranged from 71 to 90%. Positive predictive values ranged from 50 to 83%; it was unreliable for children < 12 mos (50%) and patients with emesis plus respiratory problems (64%), who were, significantly, the youngest. Reflux/h values were not in agreement for the same groups. Absence of agreement was found if the absolute value of RI was considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Fucosidosis is an autosomal recessive disorder caused by a deficiency of alpha-L-fucosidase. Up to now 79 cases have been described and several others identified but not yet published. The higher incidence of the disease is in Italy, where nearly 20 patients have been identified. Fourteen disease-causing mutations have been detected and four of them, Q422X, G60D, E375X, P141fs are present in more than 70% of the forty patients studied. In Italian patients, only seven mutations have been described and P141fs and G60D mutations are present in more than 50% of the cases. The P141fs mutation is absent in other ethnic groups. It has been impossible to establish genotype-phenotype correlation so far and the clinical variability of the disease cannot be explained only by genetic heterogeneity.

Therapeutic muds have been applied-at "Terme dei Papi", Viterbo-to 30 subjects with subchronic extra-articular rheumatism (S.I.R., Italy 1986). Favourable effects have been obtained in a great majority of subjects treated. Improvement was obtained concerning provoked pain, spontaneous pain as well as function of sprained joints.

A recently isolated cDNA clone from the iduronate sulfatase (IDS) gene has been used both to seed a contig of overlapping yeast artificial chromosomes (YACs) and to investigate the molecular defect in patients with Hunter syndrome (MPS II). Six YAC clones were found to span the IDS gene, and those and 14 other YACs were assembled into a 1.2-Mb contig around the gene in Xq27-q28. The physical map of the region identifies several putative CpG islands, suggesting the presence of other genes in the vicinity. DNA from a patient with a translocation breakpoint in the gene also permitted the orientation of the contig in the chromosome. Southern analysis of DNA from 25 unrelated Italian Hunter syndrome patients revealed 4 with deletions or rearrangements in the IDS gene.

Hereditary fructose intolerance (HFI) is an inborn error of metabolism caused by aldolase B deficiency. The aldolase B gene has been cloned and the following mutations causing HFI have been identified: A149P (a G----C transversion in exon 5), A174D (a C----A transversion in exon 5), L288 delta C (a base pair deletion in exon 8), and N334K (a G----C transversion in exon 9). We have investigated the occurrence of these mutations in 11 Italian patients affected by HFI using PCR and hybridisation to specific oligomers. We found that four patients were homozygous for the A149P mutation, two patients were homozygous for the A174D mutation, three patients were compound heterozygotes for both the A149P and A174D mutations, one patient was homozygous for the N334K mutation, and one patient did not show any of the reported mutations (HFI diagnosis carried out by aldolase B assay). The L288 delta C mutation has not been found in this survey.

Genomic DNA and mRNA from six unrelated Italian patients affected with fucosidosis were analyzed using two probes (AF3 and AF11B) of partial length cDNA coding for the lysosomal enzyme alpha-L-fucosidase. DNA from patient 2, digested with EcoRI, showed a variant pattern of hybridization caused by the loss of an EcoRI site. The same patient showed a markedly decreased amount of mRNA on Northern blot hybridization. Among the remaining patients, who showed no variation at the DNA level, two apparently lacked mRNA for alpha-L-fucosidase whereas the other three showed a transcript similar in size and amount to that observed in controls. These data confirm the genetic heterogeneity of the molecular defects causing fucosidosis in Italy.