Real-life effectiveness of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients previously treated with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir.

BACKGROUND: Sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is the recommended rescue therapy for patients with chronic hepatitis C infection who fail direct-acting antivirals (DAAs). Data are limited on the effectiveness of this treatment after the current first-line therapies. Our aim was to analyse the effectiveness and safety of SOF/VEL/VOX among patients failing sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB). METHODS: Retrospective multicentre study (26 Spanish hospitals), including chronic hepatitis C patients unsuccessfully treated with SOF/VEL or GLE/PIB, and retreated with SOF/VEL/VOX ± ribavirin for 12 weeks between December 2017 and December 2022. RESULTS: In total, 142 patients included: 100 (70.4%) had failed SOF/VEL and 42 (29.6%) GLE/PIB. Patients were mainly men (84.5%), White (93.9%), with hepatitis C virus genotype (GT) 3 (49.6%) and 47.2% had liver cirrhosis. Sustained virological response (SVR) was evaluated in 132 patients who completed SOF/VEL/VOX and were followed 12 weeks after end of treatment; 117 (88.6%) achieved SVR. There were no significant differences in SVR rates according to initial DAA treatment (SOF/VEL 87.9% vs. GLE/PIB 90.2%, p = 0.8), cirrhosis (no cirrhosis 90% vs. cirrhosis 87.1%, p = 0.6) or GT3 infection (non-GT3 91.9% vs. GT3 85.5%, p = 0.3). However, when considering the concurrent presence of SOF/VEL treatment, cirrhosis and GT3 infection, SVR rates dropped to 82.8%. Ribavirin was added in 8 (6%) patients, all achieved SVR. CONCLUSION: SOF/VEL/VOX is an effective rescue therapy for failures to SOF/VEL or GLE/PIB, with an SVR of 88.6%. Factors previously linked to lower SVR rates, such as GT3 infection, cirrhosis and first-line therapy with SOF/VEL were not associated with lower SVRs.

Acute kidney injury and point-of-care ultrasound in liver cirrhosis: redefining hepatorenal syndrome.

Acute kidney injury (AKI) in patients with cirrhosis is a diagnostic challenge due to multiple and sometimes overlapping possible etiologies. Many times, diagnosis cannot be made based on case history, physical examination or laboratory data, especially when the nephrologist is faced with AKI with a hemodynamic basis, such as hepatorenal syndrome. In addition, the guidelines still include generalized recommendations regarding withdrawal of diuretics and plasma volume expansion with albumin for 48 h, which may be ineffective and counterproductive and may have iatrogenic effects, such as fluid overload and acute cardiogenic pulmonary edema. For this reason, the use of new tools, such as hemodynamic point-of-care ultrasound (PoCUS), allows us to phenotype volume status more accurately and ultimately guide medical treatment in a noninvasive, rapid and individualized manner.

Rituximab is a safe and effective alternative treatment for patients with autoimmune hepatitis: Results from the ColHai registry.

BACKGROUND AND AIMS: Small series suggest that rituximab could be effective as treatment for autoimmune hepatitis (AIH), although data are scarce. We aimed to evaluate the efficacy and safety of rituximab in different cohorts of patients with AIH. METHODS: Multicentre retrospective analysis of the 35 patients with AIH and its variant forms treated with rituximab and included in the ColHai registry between 2015 and 2023. RESULTS: Most patients were female (83%), 10 (29%) had cirrhosis and four (11.4%) variant forms of AIH. Indication for rituximab were as follows: 14(40%) refractory AIH, 19(54%) concomitant autoimmune or haematological disorder, 2(6%) intolerance to prior treatments. In three (9%) subjects with a concomitant disorder, rituximab was the first therapy for AIH. Overall, 31 (89%) patients achieved or maintained complete biochemical response (CBR), including the three in first-line therapy. No difference in CBR was observed according to rituximab indication (refractory AIH 86% vs. concomitant disorders 90%, p = .824) or cirrhosis (80% vs. 92%, p = .319). Rituximab was associated with a significant reduction in corticosteroids (median dose: prior 20 vs. post 5 mg, p < .001) and the discontinuation of ≥1 immunosuppressant in 47% of patients. Flare-free rate at 1st, 2nd and 3rd year was 86%, 73% and 62% respectively. Flares were not associated with the development of liver failure and were successfully managed with repeated doses of rituximab and/or increased corticosteroids. Three (9%) patients experienced infusion-related adverse events (1 anaphylaxis and 2 flu-like symptoms) and five (14%) infections. CONCLUSION: Rituximab is safe and effective in patients with refractory AIH and those treated due to concomitant autoimmune or haematological disorders.

An algorithm based on immunotherapy discontinuation and liver biopsy spares corticosteroids in two thirds of cases of severe checkpoint inhibitor-induced liver injury.

BACKGROUND: There are few data on corticosteroids (CS)-sparing strategies for checkpoint inhibitor (ICI)-induced liver injury (ChILI). AIM: We aimed to assess the performance of a 2-step algorithm for severe ChILI, based on ICI temporary discontinuation (step-1) and, if lack of biochemical improvement, CS based on the degree of necroinflammation at biopsy (step-2). METHODS: Prospective study that included all subjects with grade 3/4 ChILI. Peripheral extended immunophenotyping was performed. Indication for CS: severe necroinflammation; mild or moderate necroinflammation with later biochemical worsening. RESULTS: From 111 subjects with increased transaminases (January 2020 to August 2023), 44 were diagnosed with grade 3 (N = 35) or grade 4 (N = 9) ChILI. Main reason for exclusion was alternative diagnosis. Lung cancer (13) and melanoma (12) were the most common malignancies. ICI: 23(52.3%) anti-PD1, 8(18.2%) anti-PD-L1, 3(6.8%) anti-CTLA-4, 10(22.7%) combined ICI. Liver injury pattern: hepatocellular (23,52.3%) mixed (12,27.3%) and cholestatic (9,20.5%). 14(32%) presented bilirubin >1.2 mg/dL. Overall, 30(68.2%) patients did not require CS: 22(50.0%) due to ICI discontinuation (step-1) and 8/22 (36.4%) based on the degree of necroinflammation (step-2). Biopsy mainly impacted on grade 3 ChILI, sparing CS in 8 out of 15 (53.3%) non-improvement patients after ICI discontinuation. CD8+ HLA-DR expression (p = 0.028), central memory (p = 0.046) were lower in CS-free managed subjects, but effector-memory cells (p = 0.002) were higher. Time to transaminases normalisation was shorter in those CS-free managed (overall: p < 0.001, grade 3: p < 0.001). Considering our results, a strategy based on ICI discontinuation and biopsy for grade 3 ChILI is proposed. CONCLUSIONS: An algorithm based on temporary immunotherapy discontinuation and biopsy allows CS avoidance in two thirds of cases of severe ChILI.

Proprioceptive innervation of the human lips.

The objective of this study was to analyze the proprioceptive innervation of human lips, especially of the orbicularis oris muscle, since it is classically accepted that facial muscles lack typical proprioceptors, that is, muscle spindles, but recently this has been doubted. Upper and lower human lips (n = 5) from non-embalmed frozen cadavers were immunostained for detection of S100 protein (to identify nerves and sensory nerve formations), myosin heavy chain (to label muscle fibers within muscle spindles), and the mechano-gated ion channel PIEZO2. No muscle spindles were found, but there was a high density of sensory nerve formations, which were morphologically heterogeneous, and in some cases resemble Ruffini-like and Pacinian sensory corpuscles. The axons of these sensory formations displayed immunoreactivity for PIEZO2. Human lip muscles lack typical proprioceptors but possess a dense sensory innervation which can serve the lip proprioception.

Assessing the rate of non-linkage to care and identifying barriers in individuals living with hepatitis B. Results of the LINK-B study.

BACKGROUND & AIMS: Hepatitis B infection is the most frequent cause of chronic hepatitis and liver cancer worldwide. Active searching for individuals with chronic hepatitis B has been proposed as a strategy to achieve the elimination of this virus. The primary aim of this study was to link to specialists HBsAg-positive individuals detected in a laboratory database and to characterize individuals who were not linked to care. METHODS: We performed a retrospective-prospective evaluation of all HBsAg-positive serum samples identified in the central laboratory of the Northern Barcelona area between January 2018 and June 2022. After reviewing the patients' clinical charts, all those not linked to care were given an appointment with a specialist. RESULTS: Medical records of 2765 different HBsAg-positive serum samples were reviewed and 2590 individuals were identified: 844 (32.6%) were not linked to a specialist, 653 were candidates for linkage, and 344 attended the specialist visit. The two main reasons why they were not under specialist care were administrative issues, such as living in another region (12.1%) and lacking contact details (4.1%), and low life expectancy (2.8%). Individuals who did not attend their scheduled visit were mainly young [38.1 ± 12.9 vs. 44.0 ± 14.0 (p < .001)], non-White European [75.3% vs. 58.1% (p < .001)] and men [70.7% vs. 56.4% (p < .001)]. CONCLUSIONS: One in every three HBsAg-positive individuals in our setting was not currently under specialist care. Of particular note, half of them had never attended a specialist consultation, an essential step for evaluating the disease and starting therapy in some countries.

Integrating viral hepatitis management into the emergency department: A further step towards viral hepatitis elimination.

Background & Aims: Many people with HCV and HBV infection are unaware of their condition, particularly at-risk and vulnerable populations who face barriers for screening and linkage to care. Emergency departments are often their only point of contact with the health system. Methods: This is a prospective study investigating HBsAg and HCV antibody testing, with reflex testing for HDV antibodies and HCV RNA, in adults attending an emergency department and requiring a blood test. Positive cases were linked to care. A cost-effectiveness analysis was performed. Results: From February 2020 to February 2022, a total of 17,560 individuals were screened. HBsAg was detected in 91 (0.5%), HCV RNA in 128 (0.7%), and HDV antibodies in two (0.01%) individuals. Nearly 40% of positive cases were unaware of their condition. Linkage to care was achieved in 42 of 56 HBsAg-positive and 45 of 69 HCV RNA-positive participants who were candidates for referral. HCV and HBV screening vs. no screening yielded 1.06 and 0.42 additional quality-adjusted life-years, respectively, with incremental cost-utility ratios of €7,629 and -€147 per quality-adjusted life-year gained, respectively, and proved even more cost-effective in patients with hepatitis C aged 40-70 years. Conclusions: On emergency department screening for hepatitis B, C, and D in Barcelona, the prevalence of HBsAg was 0.5% and HCV RNA 0.7%, approximately threefold higher than that observed in the general population. This strategy diagnosed patients with active HCV infection and no risk factors, who would not have been screened according to the current recommendations. Screening and linkage to care of viral hepatitis is cost-effective in this setting. Impact and implications: We evaluated the performance and cost-effectiveness of a viral hepatitis screening programme implemented in an emergency department, which aimed to identify and link to care people living with hepatitis B and C. Our findings reveal a threefold higher prevalence of hepatitis B and C than in the general Spanish population, possibly attributable to the role of the emergency department as the main healthcare gateway for vulnerable populations, who have a higher prevalence of viral hepatitis. Risk factors for viral hepatitis could not be identified in most people living with hepatitis B and C attending the emergency department; hence, screening beyond risk factors should be considered in hepatitis detection strategies. Emergency department screening is cost-effective for hepatitis C and is a cost-saving strategy for hepatitis B in our setting. These data should inform future updates to clinical guidelines.

Exploring somatosensory innervation of the human lip: A focus on the vermilion.

BACKGROUND: The lips are a vital component of the face and are densely innervated to perform various functions. The lip edges are covered with mucocutaneous tissue called vermilion which is particularly receptive to touch and temperature. The aim of this study was to investigate the somatosensory innervation of human lips, focusing on sensory corpuscles and the presence of mechano-gated (ASIC2, PIEZO2, and TRPV4) and thermosensing (TRPV1, TRPM2, and RPM8) ion channels within them. METHODS: Twelve intact lips (6 upper and 6 lower) were obtained from non-embalmed frozen cadavers (five females and seven males) with an age range of 60-80 years. The specimens were divided into three zones (medial, lateral, and median). The morphotypes of sensory corpuscles and their immunohistochemical profile was analysed. The occurrence of ion channels involved in mechanosensation and temperature detection was examined using various antibodies. Sensory corpuscle density was quantified in vermilion sections, and statistical analyses were conducted to assess differences between the upper and lower lips, as well as between females and males (p < 0.05). RESULTS: Different morphotypes of sensory corpuscles were identified: Ruffini-like associated with hair follicles, Meissner and glomerular corpuscles in the vermilion, and less classifiable sensory corpuscles within the mucosa. The density of sensory corpuscles in the vermilion was higher in the upper lip than in the lower lip; glomerular corpuscles predominated in the medial and median segments, whereas Meissner corpuscles were more abundant in the lateral segment. No sex-related differences were observed in the density or distribution of the two main corpuscular morphotypes. In contrast, the axons of both the glomeruli and Meissner corpuscles regularly displayed ASIC2 and PIEZO2 immunoreactivity, whereas immunoreactivity for TRPV1, TRPV4, TRPM2, and TRPV8 was absent. CONCLUSIONS: These results demonstrate that the sensory corpuscles of the vermilion are a mixture of those typical of glabrous skin mucocutaneous tissues. The presence of PIEZO2 and ASIC2 in their axons suggests that these sensory corpuscles function as mechanosensors.

Déficit adquirido de Factor XIII como causa de hemorragia masiva con compromiso de vía aérea superior en cirugía oncológica de cavidad oral / Acquired Factor XIII deficiency as a cause of massive hemorrhage with upper airway compromise in oncological surgery of the oral cavity

El diagnóstico etiológico de una hemorragia postoperatoria persistente en pacientes adultos sin antecedentes médicos de interés supone un reto a día de hoy. Dentro de las distintas causas encontramos el déficit adquirido del Factor XIII (F. XIII) de la coagulación. El déficit de este factor suele pasar desapercibido al no ser valorado en el estudio preoperatorio rutinario. Presentamos el caso de un varón de 70 años con déficit de F. XIII adquirido, no diagnosticado previamente, que tras ser intervenido por un carcinoma epidermoide de suelo de boca sufrió un sangrado de cavidad oral y cervical bilateral con compromiso de la vía aérea. (AU)

The etiological diagnosis of persistent postoperative bleeding in adult patients with no relevant medical history is currently a challenge. Among the different causes, we find the acquired deficiency of Factor XIII (F. XIII) of coagulation. The deficit of this factor usually goes unnoticed as it is not tested in the routine preoperative studies. We present the case of a 70-year-old man with previously undiagnosed acquired F. XIII deficiency who, after undergoing surgery for squamous cell carcinoma of the floor of the mouth, suffered oral and bilateral cervical bleeding causing airway compromise. (AU)

Effect of supramucosal height of a scan body and implant angulation on the accuracy of intraoral scanning: An in vitro study.

STATEMENT OF PROBLEM: Intraoral scanners (IOSs) provide a digital alternative to conventional implant impression techniques. However, the effect of the supramucosal height of the scan body and implant angulation on the accuracy of IOSs remains unclear. PURPOSE: The purpose of this in vitro study was to measure the impact of the supramucosal height of the scan body and implant angulation on the accuracy (trueness and precision) of intraoral digital implant scans in partially edentulous models. MATERIAL AND METHODS: Two maxillary partially edentulous casts with 4 implant analogs were fabricated, 1 with 4 parallel implants (P-groups) and 1 with 2 implants distally inclined 18 degrees (A-groups). An implant scan body was positioned on each implant analog (CARES RC Mono Scanbody). For each cast, 3 subgroups were determined based on the soft tissue moulage fabricated for each reference cast exposing 3 mm (P-3 and A-3 subgroups), 5 mm (P-5 and A-5 subgroups), and 7 mm (P-7 and A-7 subgroups) of the implant scan bodies. The 2 reference casts were registered by using a coordinate measurement machine and desktop scanner (7 Series Dental Wings) and then scanned using an IOS (TRIOS 4) (n=15). Linear and angular discrepancy values and root mean square (RMS) error values between the implant scan bodies measured on the reference and experimental scans were computed with an inspection software program (Geomagic). Mann-Whitney U tests with Bonferroni correction were applied for planned comparisons (α=.05/9 ≈ .006). RESULTS: For linear discrepancies, statistically significant differences were found between groups P-3 and A-3 (P=.004) and between P-7 and A-7 (P=.005). For angular discrepancies, statistically significant differences were found between groups A-3 and A-5 (P=.002) and between P-7 and A-7 (P=.003). The RMS error analysis found no statistically significant differences among the groups. CONCLUSIONS: Implant angulation of 18 degrees did not significantly affect the accuracy of the intraoral scans in terms of 6 of the 9 planned comparisons, although the angled groups had lower mean values. Also, the supramucosal height of the scan body did not significantly affect the accuracy of the intraoral scans in terms of 17 of the 18 planned comparisons. Results may vary with different implant scan body designs.

Risk factors associated with fixation-related complications in microsurgical free flap reconstruction of the mandible.

BACKGROUND: Hardware complications (loosening of screws, infection, or exposure of the plate) in mandibular reconstruction with vascularized osseous free flaps impose significant morbidity, and frequently require revision surgery. Purpose of this study was to identify possible contributing factors for hardware complications. METHODS: This is a retrospective cohort study involving case series of patients who underwent microvascular mandible reconstructions between 2000 and 2020. Patient demographics, pathological, clinical, and treatment-related factors were analyzed in univariate and multivariate analyses. RESULTS: Ninety-one patients were enrolled, encompassing 63 reconstructions with fibular free flaps, 26 reconstructions with scapular, and 2 reconstructions with iliac flaps. Rate of hardware complications and plate exposure was 14.3% and 7.7%, respectively, with a median follow-up time for extrusion of 29 months. In univariate analysis, preoperative radiotherapy (odds ratio [OR] = 6.57, p = .01), and secondary mandible reconstruction (OR = 4.3, p = .04) were significant predictors of hardware complications, and plate exposure was most frequently found in secondary reconstruction (37.5%, OR = 11.8, p = .04). Hypertension was the most commonly found comorbidity (24%), and it trended toward significance regarding plate exposure (p = .05). Only secondary mandible reconstruction was associated with osteosynthesis complications (OR = 12.53, p = .01) and plate exposure (OR = 23.86, p = .005) on multivariate analysis, while preoperative radiation therapy did not retain its relevance on plate exposure. CONCLUSION: Secondary mandible reconstructions with vascularized osseous free flaps have a higher risk of osteosynthesis complications than primary reconstructions.

La fístula carótido-cavernosa como complicación tardía del traumatismo maxilofacial y de base de cráneo / Carotid-cavernous fistula as a late complication of maxillofacial and skull base trauma

La fístula carótido-cavernosa (FCC) es una complicación rara de las fracturas craneofaciales. En la mayoría de los casos la FCC ocurre en las semanas posteriores al traumatismo1. Presentamos un caso clínico de FCC 4 meses tras reducción y osteosíntesis de fractura bilateral de tercio medio facial. Basándonos en nuestra experiencia y la bibliografía, recomendamos un periodo de 6 a 12 meses de seguimiento en pacientes con traumatismos de tercio medio de cráneo, así como la inclusión de signos de alarma de FCC en la hoja de recomendaciones de pacientes con traumatismos craneofaciales. Aunque la FCC no pone en peligro la vida del paciente, el retraso de su diagnóstico puede resultar en la pérdida de visión permanente del ojo afecto en días o semanas desde el comienzo de los síntomas, por lo que es de gran importancia su diagnóstico precoz. (AU)

Carotid-cavernous fistula (CCF) is a rare complication of craniofacial fractures. In most of the cases it occurs within a few weeks after the traumatism1. We present a late CCF clinical case 4 months after reduction and osteosynthesis of a mid-third facial bilateral fracture. Based on our experience and the literature, we recommend a follow up period of 6 to 12 months in mid third cranial fractures as well as the introduction of alarm symptoms in the patient’s information brochure. Although CCF isn´t life threatening, a late diagnosis can result in a permanent loss of vision of the affected eye within days or months since the beginning of the symptoms. This is why it is important to make an early diagnosis of this complication. (AU)

Pacinian Corpuscles as a Diagnostic Clue of Ledderhose Disease-A Case Report and Mapping of Pacinian Corpuscles of the Sole.

BACKGROUND: Plantar fibromatosis, known as Ledderhose disease, is a neoplastic disease characterized by a locally-aggressive bland fibroblastic proliferation. Although Pacinian corpuscles alterations are commonly described in palmar fibromatosis, there are still no references about Pacinian corpuscles alterations in the rarer plantar version. METHODS: We present a case report where a wide cutaneous resection, including the plantar fascia was performed, allowing a detailed study of Pacinian corpuscles. Pacinian corpuscles were analyzed using immunohistochemistry for neurofilament proteins, S100 protein, CD34, vimentin, glucose transporter 1, epithelial membrane antigen, neural-cell adhesion molecule, actin, desmin, type IV collagen, and high-affinity neurotrophin Trk-receptors. Moreover, the density and the size of the corpuscles were determined. RESULTS: A clear increase in the number (hyperplasia) of Pacinian corpuscles was evidenced in the Ledderhose disease plantar fascia in comparison with similarly aged normal subjects. Pacinian hypertrophy was not demonstrated, but a significant decrease in the number of corpuscular lamellae was noted, with a subsequent increase in the interlamellar spaces. Pacinian corpuscles from the pathological plantar fascia showed an abnormal structure and immunohistochemical profile, generally without identifiable axons, and also absence of an inner core or an intermediate layer. Moreover, other molecules related with trophic maintenance of corpuscles were also absent. Finally, a vascular proliferation was commonly noted in some corpuscles, which involved all corpuscular constituents. CONCLUSION: The observed Pacinian corpuscles hyperplasia could be considered a diagnostic clue of plantar fibromatosis.

Sensory innervation of the human palmar aponeurosis in healthy individuals and patients with palmar fibromatosis.

The human palmar aponeurosis is involved in hand proprioception, and it contains different sensory corpuscle morphotypes that serve this role. In palmar fibromatosis (classically referred to as Dupuytren's disease), the palmar aponeurosis undergoes fibrous structural changes that, presumably, also affect the nervous system, causing altered perception. We analysed the various sensory nerve formation morphotypes in the palmar aponeuroses of healthy subjects and patients with palmar fibromatosis. To do this, we used immunohistochemistry for corpuscular constituents and the putative mechanoproteins PIEZO2 and acid-sensing ion channel 2. Free nerve endings and Golgi-Mazzoni, Ruffini, paciniform and Pacinian corpuscles were identified in both the healthy and the pathological conditions. The densities of the free nerve endings and Golgi-Mazzoni corpuscles were slightly increased in the pathological tissues. Furthermore, the Pacinian corpuscles were enlarged and displayed an altered shape. Finally, there was also morphological and immunohistochemical evidence of occasional denervation of the Pacinian corpuscles, although no increase in their number was observed. Both PIEZO2 and acid-sensing ion channel 2 were absent from the altered corpuscles. These results indicate that the human palmar aponeurosis is richly innervated, and the free nerve endings and sensory corpuscles within the palmar aponeurosis undergo quantitative and qualitative changes in patients with palmar fibromatosis, which may explain the sensory alterations occasionally reported for this pathology.

ETV6-NTRK3-positive parotid mammary analogue secretory carcinoma: a case report.

INTRODUCTION: Mammary analogue secretory carcinoma (MASC) is a recent discovered entity of salivary glands tumors, reported for first time in 2010. The presence of a translocation encodes the ETS variant transcription factor 6-neurotrophic tyrosine receptor kinase (ETV6-NTRK3) gene fusion differences MASC from other tumors. CASE PRESENTATION: A 68-year-old male showed a non-painful right parotid enlargement, came from dermatology service, and followed by some facial squamous cell carcinomas. A computed tomography (CT) scan showed a 1.7×1.6 cm right parotid enlargement in superficial lobe. The patient underwent a right superficial parotidectomy. The final pathology confirmed the presence of ETV6-NTRK3-positive MASC. Complete right deep parotidectomy and functional cervical emptying were performed. DISCUSSIONS AND CONCLUSIONS: It is necessary to establish an appropriated differential diagnosis between salivary gland tumors. MASC is a low-grade malignancy cancer that sometimes can evolve to a high-grade tumor that might produce local and distance dissemination. Most times, these tumors are only treated by surgical resection and evaluating by a multidisciplinary team the need of more treatments. In our case, the patient showed a primary parotid tumor, removed surgically with free edges, and being identified as MASC. We decided to underwent neck dissection and discovered a second MASC focus on cervical salivary gland; however, there was no nodal dissemination. The patient remains disease-free after 14 months from last surgery. It is important to keep studying genetic therapy targets to ETV6-NTRK3 to obtain a new therapy line to treat those cases that require.

Functional results of swallowing and aspiration after oral cancer treatment and microvascular free flap reconstruction: A retrospective observational assessment.

This study aimed to assess the functional swallowing outcomes in cohort of oral cancer patients treated with tumor resection and reconstruction by means of microvascular free flaps. Duration from onset to the last examination was classified into three periods: less than 12 months, from 13 to 24 months, and more than 24 months. Type of feeding, dysphagia, and laryngeal aspiration were the dependent variables, and the study was mainly focused on the data from the multivariate analysis. Fifty-one patients were included in the study. Twenty-one patients had dysphagia, 11 showed stasis in vallecula and pyriform sinuses, 9 experienced laryngeal penetration, and 8 aspirations. Surgery combined with radiochemotherapy was associated with a higher prevalence of dysphagia (p = 0.03). Frequency of dysphagia was higher in the first year after treatment and less frequent after 24 months (p = 0.003). Dysphagia was associated with laryngeal penetration (p = 0.001), and this with aspiration (p < 0.0005). In conclusion, as it seems that the method of reconstruction has a major influence on swallowing, when there are relevant alternatives in the way the reconstruction is done, always the approach should be chosen that reduces dysphagia to a minimum.

The Human Cutaneous Sensory Corpuscles: An Update.

Sensory corpuscles of human skin are terminals of primary mechanoreceptive neurons associated with non-neuronal cells that function as low-threshold mechanoreceptors. Structurally, they consist of an extreme tip of a mechanosensory axon and nonmyelinating peripheral glial cells variably arranged according to the morphotype of the sensory corpuscle, all covered for connective cells of endoneurial and/or perineurial origin. Although the pathologies of sensitive corpuscles are scarce and almost never severe, adequate knowledge of the structure and immunohistochemical profile of these formations is essential for dermatologists and pathologists. In fact, since sensory corpuscles and nerves share a basic structure and protein composition, a cutaneous biopsy may be a complementary method for the analysis of nerve involvement in peripheral neuropathies, systemic diseases, and several pathologies of the central nervous system. Thus, a biopsy of cutaneous sensory corpuscles can provide information for the diagnosis, evolution, and effectiveness of treatments of some pathologies in which they are involved. Here, we updated and summarized the current knowledge about the immunohistochemistry of human sensory corpuscles with the aim to provide information to dermatologists and skin pathologists.

Verification and characterisation of human digital Ruffini's sensory corpuscles.

Ruffini's corpuscles are present as long fusiform encapsulated sensory structures in different tissues including the skin. Although physiological analyses strongly suggest their existence in glabrous digital skin, such localisation remains unconfirmed. Here, we have investigated the occurrence of typical Ruffini's corpuscles in 372 sections of human digital skin obtained from 186 subjects of both sexes and different ages (19-92 years). S100 protein, neuron-specific enolase and neurofilament proteins were detected, and the basic immunohistochemical profile of these corpuscles was analysed. Fewer than 0.3 Ruffini's corpuscles/mm2 were detected, with density distribution across the fingers being F4 > F3 > F2 > F1 > F5 and absolute values being F2 > F1 > F3 > F4 > F5. Axons displayed neuron-specific enolase immunoreactivity, glial cells forming the core contained S100 protein, and the capsule was positive for CD34 but not Glut1, demonstrating an endoneurial origin. Present results demonstrate the existence of Ruffini's corpuscles in human glabrous digital skin at very low densities. Moreover, the identified Ruffini's corpuscles share the basic immunohistochemical characteristics of other dermal sensory corpuscles.

Arch expansion with the Invisalign system: Efficacy and predictability.

BACKGROUND: In adult patients, treatment of skeletal crossbite requires combined treatment by fixed or removable appliances and orthognathic surgery. In cases of dentoalveolar crossbite, expansion can be achieved with fixed multibrackets and removable transparent aligners. Various researchers have already assessed the Invisalign system's predictability for arch expansion. However, most of this research was conducted using older appliances, making it necessary to assess the characteristics of the updated system SmartTrack. MATERIAL AND METHODS: A sample of 114 patients with transverse malocclusion were treated with SmartTrack. The predictability of the system's software (Clincheck) was assessed by comparing planned measurements (width of canines, premolars and molars rotations and inclinations) with the real measurements achieved at the end of the first treatment phase. Measurements were imported to Clincheck software to create three data sets; T1: initial measurements at start of treatment; T2: Clincheck predicted measurements at end of first treatment phase; T3: measurements taken at start of the second treatment phase. RESULTS: Widths underwent significant advances as a result of treatment. For all widths, virtual planning obtained prognoses of greater expansion than actually achieved: a mean of 0.63 mm more expansion at the canine level (p<0.001), 0.77 mm at first premolar (p<0.001), 0.81 at second premolar (p<0.001), 0.69 mm at first molar (p<0.001), and 0.25 mm at second molar (p = 0.183). All the treatment plan's estimations, with the exception of the second molar, were significantly higher than the actual outcomes. CONCLUSIONS: Aligners are an effective tool for producing arch expansion, being more effective in premolar area and less effective in canine and second molar area. Predictability was reasonable for expansion movement. Overcorrection should be considered at the virtual planning stage in order to obtain the expected outcomes.

A Model Based on Noninvasive Markers Predicts Very Low Hepatocellular Carcinoma Risk After Viral Response in Hepatitis C Virus-Advanced Fibrosis.

BACKGROUND AND AIMS: Patients with hepatitis C virus (HCV) and advanced fibrosis remain at risk of hepatocellular carcinoma (HCC) after sustained viral response (SVR) and need lifelong surveillance. Because HCC risk is not homogenous and may decrease with fibrosis regression, we aimed to identify patients with low HCC risk based on the prediction of noninvasive markers and its changes after SVR. APPROACH AND RESULTS: This is a multicenter cohort study, including patients with HCV and compensated advanced fibrosis that achieved SVR after direct antivirals. Clinical and transient elastography (TE) data were registered at baseline, 1 year, and 3 years after the end of treatment (EOT). All patients underwent liver ultrasound scan every 6 months. Patients with clinical evaluation 1 year after EOT were eligible. Univariate and multivariate Cox regression analysis were performed, and predictive models were constructed. HCC occurrence rates were evaluated by Kaplan-Meier. Nine hundred and ninety-three patients were eligible (56% male; 44% female; median age 62 years), 35 developed HCC (3.9%), and the median follow-up was 45 months (range 13-53). Baseline liver stiffness measurement (LSM) (HR 1.040; 95% CI 1.017-1.064), serum albumin (HR 0.400; 95% CI 0.174-0.923), 1-year DeltaLSM (HR 0.993; 95% CI 0.987-0.998), and 1-year FIB-4 score (HR 1.095; 95% CI 1.046-1.146) were independent factors associated with HCC. The TE-based HCC risk model predicted 0% of HCC occurrence at 3 years in patients with score 0 (baseline LSM ≤ 17.3 kPa, albumin >4.2 g/dL, and 1-year DeltaLSM > 25.5%) versus 5.2% in patients with score 1-3 (Harrell's C 0.779; log-rank 0.002). An alternative model with FIB-4 similarly predicted HCC risk. CONCLUSIONS: A combination of baseline and dynamic changes in noninvasive markers may help to identify patients with a very low risk of HCC development after SVR.