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The NLRP3 gene mutations are the cause of autosomal dominant autoinflammatory disorders (NLRP3-AID). Recently, hearing loss (HL) has been found to be the sole or major manifestation of NLRP3-AID. Here, we tested 110 autosomal dominant HL families with a custom panel of 237 HL genes and found one family carrying the NLRP3 c.1872C>G, p.Ser624Arg mutation. Functional studies revealed that this novel variant is a gain of function mutation, leading to increased activity of caspase-1 and subsequent oversecretion of proinflammatory interleukin-lb. Clinical reanalysis of the affected individuals, together with serological evidence of inflammation and pathological cochlear enhancement on FLAIR-MRI images, guided our diagnosis to atypical NLRP3-AID. The study highlights the role of genetic analysis in patients with progressive postlingual HL. This can help to identify individuals with hereditary HL as a consequence of NLRP3-AID and allow timely and effective treatment with interleukin-l-receptor antagonist. [ABSTRACT FROM AUTHOR]

Background. Grooving evidence suggests that patients could have Direct Access (DA) to physiotherapy. It represents a new model of care, which might lead to improve patients' health status and decrease cost services for healthcare compared with a secondary care referral pathway. The aim of this study is to explore the evidence regarding feasibility, effectiveness, costs, safety and patient satisfaction through DA compared to other organizational models. Methods. A systematic review was carried out through MEDLINE, CINAHL, and EMBASE databases from their inceptions until March 2018 using keywords related with DA. All articles in English, Italian or Polish comparing the modality of DA with any other organizational modality were included. Two reviewers independently selected eligible studies, extracted the data, and assessed methodological quality using the Newcastle-Ottawa Scale for cohort studies. Results. 1593 articles were initially identified, and thirteen studies met the inclusion criteria. The mean NOS score for study quality was 6.4 ± 1.4 out of a possible total score of nine points. Patients impairments and health care status, were similar through all studies. DA showed less number of physiotherapy treatments, visits to physician, imaging performed and required fewer non-steroidal anti-inflammatory drugs and secondary care. Patients were more satisfied with the service in comparison to the group referred by the physician. and costs per subject were lower. DA patients were younger, with a higher level of education; mostly, they presented a less severe clinical condition and a more acute pathologies related to the spine. No harms were reported. Only one study assessed the clinical safety of the DA. Conclusion. The findings suggest that DA to physiotherapy is feasible considering the clinical and economic point of view. However, more research is still needed due to the low evidence of the reviewed studies and to explore the clinical safety of DA. [ABSTRACT FROM AUTHOR]

Introduction: Genetically determined hearing loss may occur in an isolated or syndromic form. There is a wide range of syndromes for which hearing loss represents one of the characteristic features, such as Stickler and Alport syndrome. One of the most frequently observed inner ear malformation identified during a radiological workup of hearing loss patients is large vestibular aqueduct syndrome (LVAS). Objective: The aim of the study was to identify genetic variants that cause hearing loss in an adult female patient who was diagnosed with bilateral hearing loss, LVAS, high myopia, osteoarthritis and microhematuria. Material and methods: Next-generation sequencing of clinical exome was performed using the TruSight One sequencing kit (Illumina) on DNA isolated from the proband's blood sample. Analysis of the results focused on variants located in the genes related to hearing loss. To test for the presence of a haplotype located in the 5' region of the SLC26A4 gene (CEVA) in the proband and to confirm the presence and segregation of the identified pathogenic variants in the proband and her family members Sanger sequencing was performed. Results: Nextgeneration sequencing revealed the presence of a known COL2A1 pathogenic variant (NM_001844.4: c.1833+1G>A) causative for Stickler syndrome and one pathogenic change in COL4A5 (NM_000495.4: p.Gly624Asp/c.1871G>A) causative for Alport syndrome. In SLC26A4 (NM_000441.1: p.Leu597Ser/c.1790T>C) only one known pathogenic variant was found and the CEVA haplotype was not detected. Conclusions: Simultaneous testing of many genes using nextgeneration sequencing followed by family analysis identified a de novo pathogenic variant in the COL2A1 gene and after clinical reanalysis, the patient was diagnosed with Stickler syndrome, which is inherited in an autosomal dominant manner. The patient was found to be a carrier of a COL4A5 variant for the X-linked Alport syndrome, which explains the occurrence of microhematuria and may account for some degree of her hearing loss. The cause of LVAS still remains unknown as only one SLC26A4 pathogenic variant and no CEVA haplotype were found, and the disorder is inherited in an autosomal recessive manner. Our study identifies the presence of three rare known hearing loss syndromes in one patient and emphasizes the important role of genetic testing in guiding clinical diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Incomplete partition type 2 (IP2) encompasses enlarged vestibular aqueduct (EVA), the most frequently observed congenital inner ear malformation, cochlear hypoplasia and enlarged vestibule. In most EVA/IP2 cases congenital hearing impairment is observed. EVA/IP2 can occur in an isolated manner or in genetically determined syndromes such as Pendred syndrome, branchio-oto-renal syndrome (BOR), Waardenburg syndrome, CHARGE, distal renal tubular acidosis (RTA). Around 25% of EVA/IP2 patients carry two pathogenic SLC26A4 variants, while another 25% have only one variant. In 2017, the CEVA haplotype was identified in the 5' region of SLC26A4. CEVA's function remains unknown, and its frequency has not been assessed in Polish patients. Objective: The aim of the study was to identify genetic variants that cause hearing loss in patients with IP2. Material and methods: The genetic background of 20 probands with bilateral IP2 was analyzed by next generation sequencing (NGS) using a custom hearing loss gene panel. Presence and segregation of selected variants and CEVA haplotype was verified by Sanger sequencing. Results: Genetic testing identified the cause of IP2 in 11/20 (55%) individuals. Two pathogenic variants of the SLC26A4 gene were identified as the cause of IP2 in 5 out of 20 (20%). CEVA haplotype may be the cause of IP2 in 5/8 (63%) patients, who had only one SLC26A4 genetic variant detected in NGS. In one case IP2 were caused by pathogenic variant of the EYA1 gene, related to BOR. Conclusions: In our study 10/20 patients carry pathogenic variants in SLC26A4 which also confirms the association of IP2 occurrence with variants in this gene. The identification of CEVA may explain hearing loss caused by IP2 in a large group of patients with only one pathogenic variant found in the SLC26A4 gene. Studies on CEVA allows better understanding of its role in the phenotype. CEVA is a likely pathogenic allele linked to a milder phenotype than pathogenic SLC26A4 variants. Finding a pathogenic variant of the EYA1 gene in a patient with a phenotype matching BOR allows to consider this variant as the cause of IP2. [ABSTRACT FROM AUTHOR]

Nodular lymphoid hyperplasia is uncommon in adult patients. Associated diseases are common variable immunodeficiency (CVI) and lymphoid tissue malignancies. In this case report we focus on clinical presentation and differential diagnosis of diffuse nodular lymphoid hyperplasia of the gastrointestinal tract coexisting with selective immunoglobulin A deficiency and sarcoid -- like syndrome. [ABSTRACT FROM AUTHOR]

The evaluation of usefulness of high-resolution MRI in diagnostic process of tinnitus and review of organic causes of tinnitus. Material consisted of 400 consecutive patients referred for MRI 3T because of tinnitus as a leading or coexisting problem. MRI examinations were performed with high-resolution protocol including heavy T2-weighted images (0.5mm slice thickness) and T1-weighted post contrast images (1mm slice thickness). Relevant to tinnitus, important findings localized within CPAs, inner ears or middle ears were revealed in 18.5% of the group. Relevant to tinnitus, important findings localized in other assessable anatomical regions were revealed in 14.5% of cases. In 21% of cases MRI results influenced the decision of therapeutical process. Clinical assessment plays the key role in the work-up of patients with tinnitus. Diagnostic imaging is useful whenever there is suspicion of organic cause. Special attention should be paid to patient when tinnitus is unilateral and/ or sudden and/or coexisting with other neurologic symptoms. High resolution MRI in protocol dedicated for cerebello- pontine angle/temporal bones is the method of choice in morphological assessment of VII+VIII cranial nerves and membranous labyrinth. High-resolution MRI reveals important morphological findings relevant to tinnitus. In some cases the results influences the decision of therapeutical process. High-resolution MRI should be part of diagnostic algorithm of tinnitus whenever there is clinical suspicion of organic cause. [ABSTRACT FROM AUTHOR]

Introduction and Objective: Multiple studies showed that patients with a severe course of COVID-19 may develop cardiovascular complications. Assessment of the incidence of myocardial injury in young, physically fit male patients with no comorbidities, and asymptomatic/mild course of the disease who recovered from COVID-19., Material and Methods: A prospective, single-center, observational cohort study of 75 young (median[IQR] age 22 years) physically fit male patients, without comorbidities and smoking who recently recovered from COVID-19. Results were compared with a control group of age-matched, physically fit men with no comorbidities who tested negative for SARS-CoV-2., Results: 19(25%) patients had possible COVID-19 related myocardial injury[PCRMI] on cardiovascular magnetic resonance [CMR] including definitive myocarditis (n=1;1.3%) and possible myocarditis (n=3;4%). Other abnormalities: mildly decreased (<50%) left ventricular(LV) ejection fraction (n=4;5%), increased LV end-diastolic volume index (n=8;11%) and LV mass index (n=9;12%). Patients with PCRMI had higher NT-pro-BNP level (29 vs 20pg/mL respectively, P=0.02) and lower LV ejection fraction (55% vs 59% respectively, P=0.03). PCRMI was demonstrated in 3(27%) volunteers from the control group based on the presence of LGE (2/18%) and decreased LV ejection fraction (1/9%). No volunteer from the control group was diagnosed with definitive or possible myocarditis., Conclusions: PCRMI was a frequent finding in young, asymptomatic, physically-fit patients sans comorbidities relatively late after recovery from COVID-19. Whereas no definitive or possible myocarditis was found in the control group, LGE was relatively frequent suggesting that our findings might not be COVID-19 specific. This warrants a need for further investigation into the long-term cardiovascular consequences of COVID-19.

The most frequently observed congenital inner ear malformation is enlarged vestibular aqueduct (EVA). It is often accompanied with incomplete partition type 2 (IP2) of the cochlea and a dilated vestibule, which together constitute Mondini malformation. Pathogenic SLC26A4 variants are considered the major cause of inner ear malformation but the genetics still needs clarification. The aim of this study was to identify the cause of EVA in patients with hearing loss (HL). Genomic DNA was isolated from HL patients with radiologically confirmed bilateral EVA ( n = 23) and analyzed by next generation sequencing using a custom HL gene panel encompassing 237 HL-related genes or a clinical exome. The presence and segregation of selected variants and the CEVA haplotype (in the 5' region of SLC26A4 ) was verified by Sanger sequencing. Minigene assay was used to evaluate the impact of novel synonymous variant on splicing. Genetic testing identified the cause of EVA in 17/23 individuals (74%). Two pathogenic variants in the SLC26A4 gene were identified as the cause of EVA in 8 of them (35%), and a CEVA haplotype was regarded as the cause of EVA in 6 of 7 patients (86%) who carried only one SLC26A4 genetic variant. In two individuals with a phenotype matching branchio-oto-renal (BOR) spectrum disorder, cochlear hypoplasia resulted from EYA1 pathogenic variants. In one patient, a novel variant in CHD7 was detected. Our study shows that SLC26A4 , together with the CEVA haplotype, accounts for more than half of EVA cases. Syndromic forms of HL should also be considered in patients with EVA. We conclude that to better understand inner ear development and the pathogenesis of its malformations, there is a need to look for pathogenic variants in noncoding regions of known HL genes or to link them with novel candidate HL genes.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare tumours derived from peptidergic neurons and specialized neuroendocrine cells capable of secreting various peptides or amines. These cells may be present in endocrine tissue or diffused in the tissues of the digestive or respiratory system. The article reviews the characteristic features of NENs, with particular emphasis on skin manifestations, such as necrolytic migratory erythema (NME), tongue inflammation, angular cheilitis, venous thrombosis and alopecia in glucagonoma; "flushing", "lion face", pellagra skin symptoms, "scleroderma-like features without Raynaud's phenomenon" in carcinoid tumours. The paper also presents the clinical picture of the neuroendocrine tumour of the skin - Merkel cell carcinoma. The aim of this study was to draw attention to the need for precise and comprehensive diagnosis of the patients, with particular emphasis on skin lesions as a revelator of neuroendocrine tumours. This management allows for the early implementation of appropriate treatment., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 Termedia Sp. z o. o.)

The NLRP3 gene mutations are the cause of autosomal dominant autoinflammatory disorders (NLRP3-AID). Recently, hearing loss (HL) has been found to be the sole or major manifestation of NLRP3-AID. Here, we tested 110 autosomal dominant HL families with a custom panel of 237 HL genes and found one family carrying the NLRP3 c.1872C>G, p.Ser624Arg mutation. Functional studies revealed that this novel variant is a gain of function mutation, leading to increased activity of caspase-1 and subsequent oversecretion of proinflammatory interleukin-1β. Clinical reanalysis of the affected individuals, together with serological evidence of inflammation and pathological cochlear enhancement on FLAIR-MRI images, guided our diagnosis to atypical NLRP3-AID. The study highlights the role of genetic analysis in patients with progressive postlingual HL. This can help to identify individuals with hereditary HL as a consequence of NLRP3-AID and allow timely and effective treatment with interleukin-1-receptor antagonist., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Oziębło, Leja, Jeznach, Orzechowska, Skirecki, Więsik-Szewczyk, Furmanek, Bałdyga, Skarżyński and Ołdak.)

The bacterial pathogen Yersinia pestis gave rise to devastating outbreaks throughout human history, and ancient DNA evidence has shown it afflicted human populations as far back as the Neolithic. Y. pestis genomes recovered from the Eurasian Late Neolithic/Early Bronze Age (LNBA) period have uncovered key evolutionary steps that led to its emergence from a Yersinia pseudotuberculosis-like progenitor; however, the number of reconstructed LNBA genomes are too few to explore its diversity during this critical period of development. Here, we present 17 Y. pestis genomes dating to 5,000 to 2,500 y BP from a wide geographic expanse across Eurasia. This increased dataset enabled us to explore correlations between temporal, geographical, and genetic distance. Our results suggest a nonflea-adapted and potentially extinct single lineage that persisted over millennia without significant parallel diversification, accompanied by rapid dispersal across continents throughout this period, a trend not observed in other pathogens for which ancient genomes are available. A stepwise pattern of gene loss provides further clues on its early evolution and potential adaptation. We also discover the presence of the flea-adapted form of Y. pestis in Bronze Age Iberia, previously only identified in in the Caucasus and the Volga regions, suggesting a much wider geographic spread of this form of Y. pestis. Together, these data reveal the dynamic nature of plague’s formative years in terms of its early evolution and ecology.

Human culture, biology, and health were shaped dramatically by the onset of agriculture ∼12,000 y B.P. This shift is hypothesized to have resulted in increased individual fitness and population growth as evidenced by archaeological and population genomic data alongside a decline in physiological health as inferred from skeletal remains. Here, we consider osteological and ancient DNA data from the same prehistoric individuals to study human stature variation as a proxy for health across a transition to agriculture. Specifically, we compared “predicted” genetic contributions to height from paleogenomic data and “achieved” adult osteological height estimated from long bone measurements for 167 individuals across Europe spanning the Upper Paleolithic to Iron Age (∼38,000 to 2,400 B.P.). We found that individuals from the Neolithic were shorter than expected (given their individual polygenic height scores) by an average of −3.82 cm relative to individuals from the Upper Paleolithic and Mesolithic (P = 0.040) and −2.21 cm shorter relative to post-Neolithic individuals (P = 0.068), with osteological vs. expected stature steadily increasing across the Copper (+1.95 cm relative to the Neolithic), Bronze (+2.70 cm), and Iron (+3.27 cm) Ages. These results were attenuated when we additionally accounted for genome-wide genetic ancestry variation: for example, with Neolithic individuals −2.82 cm shorter than expected on average relative to pre-Neolithic individuals (P = 0.120). We also incorporated observations of paleopathological indicators of nonspecific stress that can persist from childhood to adulthood in skeletal remains into our model. Overall, our work highlights the potential of integrating disparate datasets to explore proxies of health in prehistory.

To date, objective measurements and psychophysical experiments have been used to measure frequency dependent basilar membrane (BM) delays in humans; however, in vivo measurements have not been made. This study aimed to measure BM delays by performing intracochlear electrocochleography in cochlear implant recipients. Sixteen subjects with various degrees of hearing abilities were selected. Postoperative Computer Tomography was performed to determine electrode locations. Electrical potentials in response to acoustic tone pips at 0.25, 0.5, 1, 2, and 4 kHz and clicks were recorded with electrodes at the frequency specific region. The electrode array was inserted up to the characteristic cochlear frequency region of 250 Hz for 6 subjects. Furthermore, the array was inserted in the region of 500 Hz for 15 subjects, and 1, 2, and 4 kHz were reached in all subjects. Intracochlear electrocochleography for each frequency-specific tone pip and clicks showed detectable responses in all subjects. The latencies differed among the cochlear location and the cochlear microphonic (CM) onset latency increased with decreasing frequency and were consistent with click derived band technique. Accordingly, BM delays in humans could be derived. The BM delays increased systematically along the cochlea from basal to apical end and were in accordance with Ruggero and Temchin, 2007.

Enamel Hypoplasia (EH) is known to be a useful indicator for wide range of detrimental factors in early childhood in past populations, such as nutritional disturbances, mechanical trauma, disease, metabolic, and/or genetic disorders. EH may be divided into three categories: pits, grooves, and lines, where the last two are referred to as "Linear Enamel Hypoplasia" (LEH). The regularity of enamel formation allows retrospective determination of the age of LEH formation. The current article reviews and compares the best-known methods used to estimate age at LEH formation and provides a new computational tool. Growth curves for canines and incisors were developed based on tooth growth tables by previous authors. Optimal models were selected using the Akaike Information Criterion. A Microsoft Excel spreadsheet was created to calculate age at LEH formation using the most common methods. All method results were compared with an archaeological sample (44 teeth of 18 individuals from an early modern cemetery from Wrocław, Poland) and a theoretical model. The results of the methods were compared pairwise with Bland-Altman plots. The current article provides a quick and easy-to-use tool for analyzing LEH chronology and comparing the results of different methods. As shown by the Bland-Altman plots, most methods provide approximately consistent results for LEHs formed at around 2-3 years of age. However, LEHs formed particularly early or late are more prone to discrepancies between different methods. Comparison of the age at LEH formation obtained by different methods should be done carefully - and the new LEH calculation tool with optimized equations provided in this publication can facilitate this process., (© 2021 Anatomical Society.)

Uniparentally-inherited markers on mitochondrial DNA (mtDNA) and the non-recombining regions of the Y chromosome (NRY), have been used for the past 30 years to investigate the history of humans from a maternal and paternal perspective. Researchers have preferred mtDNA due to its abundance in the cells, and comparatively high substitution rate. Conversely, the NRY is less susceptible to back mutations and saturation, and is potentially more informative than mtDNA owing to its longer sequence length. However, due to comparatively poor NRY coverage via shotgun sequencing, and the relatively low and biased representation of Y-chromosome variants on capture assays such as the 1240 k, ancient DNA studies often fail to utilize the unique perspective that the NRY can yield. Here we introduce a new DNA enrichment assay, coined YMCA (Y-mappable capture assay), that targets the "mappable" regions of the NRY. We show that compared to low-coverage shotgun sequencing and 1240 k capture, YMCA significantly improves the mean coverage and number of sites covered on the NRY, increasing the number of Y-haplogroup informative SNPs, and allowing for the identification of previously undiscovered variants. To illustrate the power of YMCA, we show that the analysis of ancient Y-chromosome lineages can help to resolve Y-chromosomal haplogroups. As a case study, we focus on H2, a haplogroup associated with a critical event in European human history: the Neolithic transition. By disentangling the evolutionary history of this haplogroup, we further elucidate the two separate paths by which early farmers expanded from Anatolia and the Near East to western Europe., (© 2021. The Author(s).)

Background: Genetically determined prelingual hearing loss (HL) may occur in an isolated or syndromic form., Objective: The aim of the study was to unravel the genetic cause of medical problems in a 21-year-old woman, whose phenotypic presentation extended beyond Stickler syndrome and included enlarged vestibular aqueduct (EVA) and persistent microhematuria., Methods and Results: After sequencing of clinical exome, a known de novo COL2A1 pathogenic variant (c.1833+1G>A, p.?) causative for Stickler syndrome and one paternally inherited pathogenic change in COL4A5 (c.1871G>A, p.Gly624Asp) causative for X-linked Alport syndrome were found. No pathogenic variants, including those within the SLC26A4 5' region (Caucasian EVA haplotype), explaining the development of EVA, were identified., Conclusions: The study reveals a multilocus genomic variation in one individual and provides a molecular diagnosis of two HL syndromes that co-occur in the proband independent of each other. For the third entity, EVA, no etiological factor was identified. Our data emphasize the relevance of detailed clinical phenotyping for accurate genotype interpretation. Focus on broadening the phenotypic spectrum of known genetic syndromes may actually obscure patients with multiple molecular diagnoses., (© 2020 S. Karger AG, Basel.)

Background: In this study, a method to estimate number of electrodes in the acoustic region of Electric Acoustic Stimulation (EAS) subjects was proposed. Aims/Objectives: To develop and validate an anatomy-based method for EAS subjects to estimate the number of electrodes within the acoustic region. Material and methods: The postoperative CTs of adults with various degree of hearing implanted with lateral wall electrodes with mean insertion depth of 23.9 mm (18.0-28.2 mm) and mean insertion angle of 505° (355-695°) were evaluated. Results: The difference between the estimated and measured angle varied between -18 and 25°, with a mean of 0.9°. For the insertion angle of 230° and higher, the maximum difference was 24°. Taking this uncertainty into account, all electrodes in the acoustic region were predicted correctly. Conclusions and significance: The method decides on non-overlapping acoustic and electric stimulation in terms of place in the cochlea. With the accuracy of 0.84 mm for the electrode arrays inserted for more than 230°, the method was sufficient to estimate the exact number of electrodes in the acoustic region of cochlear implantees. The benefit of this method may be in fitting of EAS subjects with some portion of the electrode array in the acoustic region.

Introduction: Since the first reported case of coronavirus disease 2019 (COVID‑19) in Poland, the worldwide pandemic has spread throughout the country, leading to many hospital admissions. There has been an urgent need to determine clinical characteristics of Polish patients with laboratory‑confirmed severe acute respiratory syndrome coronavirus 2 (SARS‑CoV 2) infection in the clinical setting., Objectives: The aim of this retrospective study was to outline characteristics and short‑ term outcomes of SARS‑CoV‑2-positive patients., Patients and Methods: We retrospectively assessed 169 consecutive patients with laboratory‑ confirmed COVID‑ 19 with regard to their clinical manifestations, radiological findings, treatment, complications, and outcomes., Results: Of the 169 patients, more than half was aged 65 years or older (88; 52.1%), 51.5% were male, and 78.3% had comorbidities. The majority of patients (106; 62.7%) were transferred from outbreak locations in medical facilities. The most common symptoms on admission were fever (42%), shortness of breath (35%), and fatigue (33%). Twenty seven (15.4%) patients required intensive care unit admission. Overall mortality was 26.3% (n = 46) and was significantly higher in patients transferred from other facilities (38 out of 106; 35.8%), than in patients admitted directly to the hospital (8 out of 63; 12.69%; P <0.001). Seventeen out of 29 patients admitted to the intensive care unit died (mortality, 58.6%), including 30 out of 41 patients with acute respiratory distress syndrome (73.2% mortality rate)., Conclusions: Polish patients with COVID‑19 have similar characteristics and risk factors for adverse outcomes to those observed in countries in which outbreaks occurred earlier. Significantly higher mortality in patients transferred from other centers warrants special attention and transfer policy should be verified.

Competing Interests: The authors declare no conflict of interest.

Objectives: The intracochlear electrocochleography (ECoG) could be recorded directly from the cochlear implant (CI) electrode in CI recipients with residual hearing. The primary objective of this study is to identify the most sensitive frequency to record cochlear microphonics (CM) in CI users with a wide degree of hearing abilities and deep electrode insertion. The secondary objective is to identify the optimum location within the cochlea to record intracochlear potentials., Materials and Methods: CMs were recorded from the CI electrodes in eight females and eight males implanted with CIs Pulsar, Concerto, or Sonata, Med-El Corp., Results: Among the tone pips of various frequencies, 1k or 500 Hz were the most sensitive for CI users. The most sensitive place in the cochlea to record the CM potentials depended on the tone frequency used. The deeper into the cochlea the mean maximum CM peak-to-peak amplitude was measured, the lower the stimulating tone frequency was., Conclusion: The most optimal recording parameters identified for intracochlear CM recording can be useful for intraoperative and postoperative monitoring of cochlear health in CI users with residual hearing.

Purpose: Caseous calcification is a relatively uncommon variant of calcification of the mitral annulus. The purpose of the study was to assess characteristic radiological features of caseous calcification of the mitral annulus (CCMA) using computed tomography (CT) and compare the usefulness of CT and transthoracic echocardiogram (TTE) in a diagnosis of CCMA., Material and Methods: Seventeen patients with CCMA, who underwent TTE and CT, were analysed. The following features of CCMA were evaluated: location, size, attenuation, enhancement after contrast administration, and margins., Results: In all cases TTE visualised an echo-dense structure with an irregular appearance involving the mitral valve annulus. In five cases the acoustic shadowing artefact was visible, and in four cases the mass contained central areas of echolucency. Eleven patients had valve disease.On CT CCMA appeared as a round mass in one case, in 10 cases as an oval mass, and in six patients it had a semilunar shape.In all cases on unenhanced CT, CCMA appeared as a hyperdense mass. On enhanced CT, CCMA in 10 cases (58.8%) had a hypodense centre, and in 7seven (41.2%) it had a hyperdense centre without enhancement after contrast administration. A hyperdense rim was observed in all cases except one patient., Conclusions: In cases of the atypical appearance of CCMA on TTE, CT can lead to a definitive diagnosis. The combination of unenhanced CT and after IV contrast administration scans allows for recognition and distinction of CCMA from other pathologies, while TTE allows for assessment of additional valve dysfunction., Competing Interests: The authors report no conflict of interest.

Background: Grooving evidence suggests that patients could have Direct Access (DA) to physiotherapy. It represents a new model of care, which might lead to improve patients' health status and decrease cost services for healthcare compared with a secondary care referral pathway. The aim of this study is to explore the evidence regarding feasibility, effectiveness, costs, safety and patient satisfaction through DA compared to other organizational models., Methods: A systematic review was carried out through MEDLINE, CINAHL, and EMBASE databases from their inceptions until March 2018 using keywords related with DA. All articles in English, Italian or Polish comparing the modality of DA with any other organizational modality were included. Two reviewers independently selected eligible studies, extracted the data, and assessed methodological quality using the Newcastle-Ottawa Scale for cohort studies., Results: 1593 articles were initially identified, and thirteen studies met the inclusion criteria. The mean NOS score for study quality was 6.4 ± 1.4 out of a possible total score of nine points. Patients impairments and health care status, were similar through all studies. DA showed less number of physiotherapy treatments, visits to physician, imaging performed and required fewer non-steroidal anti-inflammatory drugs and secondary care. Patients were more satisfied with the service in comparison to the group referred by the physician. and costs per subject were lower. DA patients were younger, with a higher level of education; mostly, they presented a less severe clinical condition and a more acute pathologies related to the spine. No harms were reported. Only one study assessed the clinical safety of the DA., Conclusion: The findings suggest that DA to physiotherapy is feasible considering the clinical and economic point of view. However, more research is still needed due to the low evidence of the reviewed studies and to explore the clinical safety of DA.