Anaesthetic challenging in microsurgical flap reconstruction: a systematic review

Background: Anaesthetic management for microvascular reconstructive surgery is challenging and clearly affects the risk of major complications such as flap hypo-perfusion. In this systematic review we explore recent (last 7 years) clinical evidences related to perioperative management and anaesthetic controversy of patients undergoing microvascular reconstructive surgery, especially focused on head and neck surgery with free flaps (FF) and breast reconstructive surgery with deep inferior epigastric perforator flap (DIEP-flap). Methods: A literature search of published clinical studies between 2011 and 2018 was conducted, yielding a total of 4307 papers. Only 150 were eligible, according inclusion and exclusion criteria. Results: 62 studies were selected for this review and categorized in 3 groups: preoperative-intraoperative- postoperative anaesthetic management and areas of controversy for patients undergoing head and neck surgery with FF and breast reconstructive surgery with DIEP-flap. Discussion: Anaesthetic management for flap reconstructive surgery remains an open field of interest with limited evidences regarding a standard care. Main components of research currently are: the need to join standard multidisciplinary enhanced recovery pathways, as well as the necessity to develop a standard intraoperative management. In theatre, the recent hemodynamic parameter “Hypotension Probability Indicator” (HPI) is promising: the advantage to predict a drop in the mean arterial pressure can be more effective than a fluid therapy titrated to maintain SVV less than 13%. Prospective studies are necessary to clarify

Investigation on reference frames and time systems in Multi-GNSS

Receivers able to track satellites belonging to different GNSSs (Global Navigation Satellite Systems) are available on the market. To compute coordinates and velocities it is necessary to identify all the elements that contribute to interoperability of the different GNSSs. For example the timescales kept by different GNSSs have to be aligned. Receiver-specific biases, or firmware-dependent biases, need to be calibrated. The reference frame used in the representation of the orbits must be unique. In this paper we address the interoperability issues from the standpoint of a Single Point Positioning (SPP) user, i.e., using pseudoranges and broadcast ephemeris. The biases between GNSSs timescales and receiver-dependent biases are analyzed for a set of 31 MGEX (Multi-GNSS Experiment) stations over a time span of more than three years. Time series of biases between timescales of GPS (Global Positioning System), GLONASS (Global Navigation Satellite System), Galileo, BeiDou, QZSS (Quasi-Zenith Satellite System), SBAS (Satellite Based Augmentation System) and NAVIC (Navigation with Indian Constellation) are investigated, in addition to the identification of events like discontinuity of receiver-dependent biases due to firmware updating. The GPS broadcast reference frame is shown to be aligned to the one (IGS14) realized by the precise ephemeris of CODE (Center for Orbit Determination in Europe) to within 0.1 m and 2 milliarcsec, with values dependent on whether IIR-A, IIR-B/M or IIF satellite blocks are considered. Larger offsets are observed for GLONASS, up to 1 m for GLONASS K satellites. For Galileo the alignment of the broadcast orbit to IGS14/CODE is again at the 0.1 m and several milliarcsec level, with the FOC (Full Operational Capability) satellites slightly better than IOV (In Orbit Validation). For BeiDou an alignment of the broadcast frame to IGS14/CODE comparable to GLONASS is observed, regardless of whether IGSO (Inclined Geosynchronous Orbit) or MEO (Medium Earth Orbit) satellites are considered. For all satellites, position differences according to the broadcast ephemeris relative to IGS14/CODE orbits are projected to the radial, along-track and crosstrack triad, with the largest periodic differences affecting mostly the along track component. Sudden discontinuities at the level of up to 1 m and 2–3 ns are observed for the along-track component and the satellite clock, respectively. The time scales of GLONASS, Galileo, QZSS, SBAS and NAVIC are very closely aligned to GPS, with constant offsets depending on receiver type. The offset of the BeiDou time scale to GPS has an oscillatory pattern with peak-to-peak values up to 100 ns. To characterize receiver-dependent biases the average of six Septentrio receivers is taken as reference, and relative offsets of the other receiver types are investigated. These receiver-dependent biases may depend on the individual station, or for the same station on the update of the firmware. A detailed calibration history is presented for each multiGNSS station studied

OPA1-related auditory neuropathy: site of lesion and outcome of cochlear implantation.

Hearing impairment is the second most prevalent clinical feature after optic atrophy in Dominant Optic Atrophy associated with mutations in the OPA1 gene. In this study we characterized the hearing dysfunction in OPA1-linked disorders and provided effective rehabilitative options to improve speech perception. We studied two groups of OPA1 subjects, one comprising 11 patients (7 males; age range 13-79 years) carrying OPA1 mutations inducing haploinsufficiency, the other, 10 subjects (3 males; age range 5-58 years) carrying OPA1 missense mutations. Both groups underwent audiometric assessment with pure tone and speech perception evaluation, and otoacoustic emissions and auditory brainstem response recording. Cochlear potentials were recorded through transtympanic electrocochleography from the group of patients harboring OPA1 missense mutations and were compared to recordings obtained from 20 normally-hearing controls and from 19 subjects with cochlear hearing loss. Eight patients carrying OPA1 missense mutations underwent cochlear implantation. Speech perception measures and electrically-evoked auditory nerve and brainstem responses were obtained after one year of cochlear implant use. Nine out of 11 patients carrying OPA1 mutations inducing haploinsufficiency had normal hearing function. In contrast, all but one subject harboring OPA1 missense mutations displayed impaired speech perception, abnormal brainstem responses and presence of otoacoustic emissions consistent with auditory neuropathy. In electrocochleography recordings, cochlear microphonic had enhanced amplitudes while summating potential showed normal latency and peak amplitude consistent with preservation of both outer and inner hair cell activities. After cancelling the cochlear microphonic, the synchronized neural response seen in both normally-hearing controls and subjects with cochlear hearing loss was replaced by a prolonged, low-amplitude negative potential that decreased in both amplitude and duration during rapid stimulation consistent with neural generation. The use of cochlear implant improved speech perception in all but one patient. Brainstem potentials were recorded in response to electrical stimulation in five subjects out of six, whereas no compound action potential was evoked from the auditory nerve through the cochlear implant. These findings indicate that underlying the hearing impairment in patients carrying OPA1 missense mutations is a disordered synchrony in auditory nerve fiber activity resulting from neural degeneration affecting the terminal dendrites. Cochlear implantation improves speech perception and synchronous activation of auditory pathways by by-passing the site of lesion

Legionnaires' disease in Italy: results of the epidemiological surveillance from 2000 to 2011

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Regressing multiple viral plaques and skin fragility syndrome in a cat coinfected with FcaPV2 and FcaPV3

Feline viral plaques are uncommon skin lesions clinically characterized by multiple, often pigmented, and slightly raised lesions. Numerous reports suggest that papillomaviruses (PVs) are involved in their development. Immunosuppressed and immunocompetent cats are both affected, the biological behavior is variable, and the regression is possible but rarely documented. Here we report a case of a FIV-positive cat with skin fragility syndrome and regressing multiple viral plaques in which the contemporary presence of two PV types (FcaPV2 and FcaPV3) was demonstrated by combining a quantitative molecular approach to histopathology. The cat, under glucocorticoid therapy for stomatitis and pruritus, developed skin fragility and numerous grouped slightly raised nonulcerated pigmented macules and plaques with histological features of epidermal thickness, mild dysplasia, and presence of koilocytes. Absolute quantification of the viral DNA copies (4555 copies/microliter of FcaPV2 and 8655 copies/microliter of FcaPV3) was obtained. Eighteen months after discontinuation of glucocorticoid therapy skin fragility and viral plaques had resolved.The role of the two viruses cannot be established and it remains undetermined how each of the viruses has contributed to the onset of VP; the spontaneous remission of skin lesions might have been induced by FIV status change over time due to glucocorticoid withdraw and by glucocorticoids withdraw itself

Biomarkers and prognostic stratification in psoriatic arthritis

In rheumatic diseases, biomarkers may serve as surrogate endpoints for diagnosis, prognosis, disease activity, therapeutic response and disease outcome. In recent years a great effort has been made to identify useful tools to establish early diagnosis, prognosis and therapeutic response especially in rheumatoid arthritis (RA). In psoriatic arthritis (PsA) serological biomarkers have been frequently borrowed from RA, but this approach have sometimes lead to inappropriate choices of biomarkers and incorrect conclusions. Furthermore, the heterogeneous spectrum of articular manifestation of PsA and the variable course of the disease can make diagnosis and prognosis difficult. Recently, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) identified two key areas for biomarkers development in psoriasis and PsA: the diagnosis of the articular disease in patients with psoriasis and the evaluation of joint damage in PsA. In this review we revised the currently available and the new potential markers for PsA, such as serum, genetic, cellular and histological biomarkers, clinical and imaging data, with particular attention on the prognostic aspect in order to identify progressive disease suitable for a more aggressive treatment

Biotechnological drugs : the breakthrough in autoimmune rheumatic conditions

Editoria

Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions

Background: An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have been associated with variably overlapping phenotypes of Leber’s hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads also to a Leigh-like phenotype. Case presentation: A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1 mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H background, were also present. Conclusion: This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the primary LHON mutation

POS0575 THE PATIENT GLOBAL ASSESSMENT (PGA) OF DISEASE ACTIVITY COLLECTS DIFFERENT INFORMATION IN EARLY COMPARED TO ESTABLISHED RHEUMATOID ARTHRITIS

Background:The patient global assessment (PGA) is the most widely used patient-reported measure in rheumatoid arthritis (RA), being a component of disease activity scores and definitions of remission. Studies have however shown that, at least in established RA, PGA is mostly associated with pain, functional limitation, psychological distress and comorbidities, rather than with objective measures of inflammation. As such, the inclusion of PGA as a driver of intensification of immunosuppressive therapy is been questioned. Determinants of PGA may however differ in the earliest stages of RA, when pain processing mechanisms and damage accrual have not occurred yet. Whether the association of PGA with disease activity in RA changes over time is at present undetermined.Objectives:To analyze the associations between PGA and disease activity measures in patients with RA across different phases of the disease.Methods:1.002 RA patients from two independent cohorts were included: 1) a prospective longitudinal cohort of early RA (5 years) (n=401) with inadequate response to methotrexate. Determinants of PGA were assessed by Pearson's correlation coefficients and multivariable linear regression.Results:In early RA, median (IQR) symptom duration at inclusion was 15 (9-27) weeks, 71.5% of the patients were female, 49.3% were autoantibody-positive, and 30% had radiographic evidence of ≥1 erosion. The mean (SD) DAS28 was 4.94 (1.19), and the mean (SD) PGA 57.6 (26.6). The proportion of patients at least in low disease activity (DAS28 0.40) at all time points, and were independent of other co-variates (Table 1). Swollen joints (SJC28) were independently and directly associated with PGA at all time points until 12 months, whilst the association become indirect at 24 months (Table 1). In ACPA-positive patients, PGA at 6 and 12 months was weakly but still significantly associated with SJC28 even in low disease activity states (adj r 0.15 and 0.13, p<0.05). Patients with established RA had a mean [SD] DAS28 of 5.3 [1.2] and were ACPA-positive in 69.6% of the cases. Independent determinants of PGA were pain, HAQ and tender joints, whilst no associations with SJC28 and acute phase reactants were found neither in the overall cohort nor in ACPA-positive patients.Conclusion:In established RA, PGA appears mostly related to factors outside the core domains of disease activity. In contrast, in the early phases of the disease, PGA may more strictly collect information on inflammatory-related symptoms. Better understanding of the relationship between patient reported outcomes and disease activity in the various phases of RA may thus be needed before introducing definitive changes in the current definitions of disease activity.References:[1]Nikiphorou E et al. Arthritis Res Ther 2016;18:251[2]Ferreira RJO et al. Ann Rheum Dis 2019;78:e109.Table 1.Associations of PGA in early RA at different time points0 months6 months12 months24 monthsr (95% CI)pr (95% CI)pr (95% CI)pr (95% CI)pVAS pain0.74 (0.70-0.77)<0.0010.83 (0.80-0.86)<0.0010.84 (0.80-0.86)<0.0010.83 (0.79-0.87)<0.001HAQ0.47 (0.41-0.54)<0.0010.54 (0.46-0.62)<0.0010.57 (0.50-0.63)<0.0010.50 (0.41-0.59)<0.001SJC280.27 (0.19-0.35)<0.0010.27 (0.18-0.35)<0.0010.21 (0.12-0.30)<0.0010.23 (0.13-0.33)<0.001TJC280.34 (0.27-0.41)<0.0010.39 (0.31-0.47)<0.0010.39 (0.30-0.46)<0.0010.30 (0.20-0.40)<0.001CRP0.08 (0.00-0.17)0.050.09 (0.00-0.19)0.070.19 (0.10-0.28)<0.0010.03 (0.09-0.14)0.63β standpβ standpβ standpβ standpVAS pain0.66<0.0010.76<0.0010.74<0.0010.80<0.001HAQ0.20<0.0010.180.010.200.030.220.003SJC280.170.030.150.040.110.04----TJC28----------------CRP------------Acknowledgements:I have no acknowledgements to declare.Disclosure of Interests:Ludovico De Stefano: None declared, Serena Bugatti Speakers bureau: BMS, Lilly, Sanofi, Pfizer, Galapagos, Bernardo D'Onofrio: None declared, Ennio Favalli Speakers bureau: AbbVie, MSD, Novartis, Pfizer, UCB Pharma, Antonio Manzo: None declared, Roberto Caporali Speakers bureau: AbbVie, BMS, Celgene, HSD, Lilly, Pfizer, Roche, UCB Pharma, Carlomaurizio Montecucco Speakers bureau: BMS, Lilly, Sanofi, Pfizer, Galapagos, Roche, Novarti

A second case with the V374A KCND3 pathogenic variant in an Italian patient with early-onset spinocerebellar ataxia

Background and Objectives To date, approximately 20 heterozygous mainly loss-of-function variants in KCND3 have been associated with spinocerebellar ataxia (SCA) type 19 and 22, a clinically heterogeneous group of neurodegenerative disorders. We aimed at reporting the second patients with the V374A KCND3 mutation from an independent family, confirming its pathogenic role. Methods We describe the clinical history of a patient with SCA and conducted genetic investigations including mitochondrial DNA analysis and exome sequencing. Results This male patient was reported to have unstable gait with tremors at the lower limbs and dysarthric speech since childhood. A neurologic examination also showed dysarthria, nystagmus, action tremor, dysmetria, and weak deep tendon reflexes. He had marked cerebellar atrophy at brain MRI, more evident at vermis. Molecular analysis, including exome sequencing and an in silico panel analysis of genes associated with SCA, revealed the c.1121T&gt;C [p.V374A] mutation in KCND3. Discussion This report consolidates the pathogenicity of the V374A KCND3 mutation and suggests that the ataxic paroxysmal exacerbations are not a key phenotypic feature of this mutation