Special articleFear of illness in Kafka's Metamorphosis.

This year marks 100 years since the death of Franz Kafka. Often in general medicine, and internal medicine in particular, doctors face situations in which they position themselves as the only guarantor of the patient in relation to society and how it conceives the disease. Many times, patients come to us without a diagnosis or with the fear of it; sometimes also rejected by their environment. This short text addresses this current topic, paying tribute to the brilliant writer and his best-known work, Metamorphosis.

Characteristics of pseudophakic retinal detachment and risk factors of recurrence.

BACKGROUND: The present study was designed to gain knowledge about the prognostic factors and evolution of pseudophakic retinal detachment (PRD) and to analyse the main characteristics of PRD, such as the mean time to retinal detachment following cataract surgery, as well as the clinical factors associated with the risk of recurrence and worse anatomical and functional outcomes. METHODS: This was a retrospective monocentric study of 330 patients with PRD who underwent surgery between 2012 and 2020. All patients were pseudophakic and were referred for retinal detachment surgery at Donostia University Hospital (Terciary Hospital, Spain). RESULTS: The mean age of the patients at the time of phacoemulsification was 63.06 ±â€¯10.8 years, and 49.09% of them had moderate myopia [axial length (AL) (23.5-26.5 mm)]. In our series, macular detachment was evident in 69.09% (n = 228) of the patients. The mean time that elapsed between phacoemulsification and PRD surgery was 4.04 ±â€¯4.17 years, which was reduced by half in the event of surgical complications (2.24 ±â€¯2.65). The rate of PRD was 28.79%. The anatomical results in terms of retinal reapplication were better with the combination of vitrectomy and scleral buckling (83.1% vs. 70.5%) (p = 0,127) compared with vitrectomy. The variables associated with a higher risk of recurrence were male sex (hazard ratio (HR) = 1.75), macular detachment (HR = 2.00) and the presence of proliferative vitreoretinopathy (PVR) (HR = 3.21). CONCLUSIONS: PRD usually occurs within 4 years of phacoemulsification, although it may occur significantly earlier in the event of surgical complications. Macular involvement, PVR, and male sex are all associated with a higher risk of PRD recurrence.

Bio-Inspired Fluorescent Calcium Sulfate for the Conservation of Gypsum Plasterwork.

In this work, the potential of bio-inspired strategies for the synthesis of calcium sulfate (CaSO4·nH2O) materials for heritage conservation is explored. For this, a nonclassical multi-step crystallization mechanism to understand the effect of calcein- a fluorescent chelating agent with a high affinity for divalent cations- on the nucleation and growth of calcium sulfate phases is proposed. Moving from the nano- to the macro-scale, this strategy sets the basis for the design and production of fluorescent nano-bassanite (NB-C; CaSO4·0.5H2O), with application as a fully compatible consolidant for the conservation of historic plasterwork. Once applied to gypsum (CaSO4·2H2O) plaster specimens, cementation upon hydration of nano-bassanite results in a significant increase in mechanical strength, while intracrystalline occlusion of calcein in newly-formed gypsum cement improves its weathering resistance. Furthermore, under UV irradiation, the luminescence produced by calcein molecules occluded in gypsum crystals formed upon nano-bassanite hydration allows the easy identification of the newly deposited consolidant within the treated gypsum plaster without altering the substrate's appearance.

Valine aminoacyl-tRNA synthetase promotes therapy resistance in melanoma.

Transfer RNA dynamics contribute to cancer development through regulation of codon-specific messenger RNA translation. Specific aminoacyl-tRNA synthetases can either promote or suppress tumourigenesis. Here we show that valine aminoacyl-tRNA synthetase (VARS) is a key player in the codon-biased translation reprogramming induced by resistance to targeted (MAPK) therapy in melanoma. The proteome rewiring in patient-derived MAPK therapy-resistant melanoma is biased towards the usage of valine and coincides with the upregulation of valine cognate tRNAs and of VARS expression and activity. Strikingly, VARS knockdown re-sensitizes MAPK-therapy-resistant patient-derived melanoma in vitro and in vivo. Mechanistically, VARS regulates the messenger RNA translation of valine-enriched transcripts, among which hydroxyacyl-CoA dehydrogenase mRNA encodes for a key enzyme in fatty acid oxidation. Resistant melanoma cultures rely on fatty acid oxidation and hydroxyacyl-CoA dehydrogenase for their survival upon MAPK treatment. Together, our data demonstrate that VARS may represent an attractive therapeutic target for the treatment of therapy-resistant melanoma.

Calcitriol Treatment Is Safe and Increases Frataxin Levels in Friedreich Ataxia Patients.

BACKGROUND: Calcitriol, the active form of vitamin D (also known as 1,25-dihydroxycholecalciferol), improves the phenotype and increases frataxin levels in cell models of Friedreich ataxia (FRDA). OBJECTIVES: Based on these results, we aimed measuring the effects of a calcitriol dose of 0.25 mcg/24h in the neurological function and frataxin levels when administered to FRDA patients for a year. METHODS: 20 FRDA patients where recluted and 15 patients completed the treatment for a year. Evaluations of neurological function changes (SARA scale, 9-HPT, 8-MWT, PATA test) and quality of life (Barthel Scale and Short Form (36) Health Survey [SF-36] quality of life questionnaire) were performed. Frataxin amounts were measured in isolated platelets obtained from these FRDA patients, from heterozygous FRDA carriers (relatives of the FA patients) and from non-heterozygous sex and age matched controls. RESULTS: Although the patients did not experience any observable neurological improvement, there was a statistically significant increase in frataxin levels from initial values, 5.5 to 7.0 pg/µg after 12 months. Differences in frataxin levels referred to total protein levels were observed among sex- and age-matched controls (18.1 pg/µg), relative controls (10.1 pg/µg), and FRDA patients (5.7 pg/µg). The treatment was well tolerated by most patients, and only some of them experienced minor adverse effects at the beginning of the trial. CONCLUSIONS: Calcitriol dosage used (0.25 mcg/24 h) is safe for FRDA patients, and it increases frataxin levels. We cannot rule out that higher doses administered longer could yield neurological benefits. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Superior semicircular canal dehiscence in relation with the superior petrosal sinus: our experience, surgical management and systematic review of literature.

PURPOSE: Most of Superior Semicircular Canal Dehiscence (SSCD) are located in the apical region of the SSC. However, in a small number of cases, it may be situated in the medial wall, causing the SSC to contact with the superior petrosal sinus (SPS). The aim of this study is to describe four patients with SSCD involving the superior petrosal sinus (SSCD-SPS) and to perform a review of the literature. METHODS: Observational retrospective study of patients diagnosed of SSCD-SPS in a tertiary referral center. A systematic review was made, identifying 7 articles in the literature. Clinical presentation, complementary test (pure-tone audiometry, PTA; vestibular evoked myogenic potential, VEMP; computed tomography, CT), therapeutic management and outcomes were reported. RESULTS: Four new cases of SSCD-SPS are reported, in three of them a transmastoid plugging was performed. 54 patients with SSCD-SPS (57 dehiscences) were reported in the literature. The most frequent symptoms were aural pressure (57.41%) and vertigo provoked by pressure/Valsalva (55.55%). Conductive hearing loss was the most common finding in PTA (47.37%). Abnormally low thresholds were observed in 59.46% of reported VEMP. Transmastoid approach was used in ten cases, middle fossa approach in four, round window reinforcement in one, and occlusion of the SPS using coils in two. CONCLUSIONS: Within SSCD, we have encountered a rare subtype characterized by its medial wall location in close proximity to the SPS. This subgroup needs special consideration as it has shown its own distinct characteristics. Regarding therapeutic management, we advocate a transmastoid approach.

The CNS relapse in T-cell lymphoma index predicts CNS relapse in patients with T- and NK-cell lymphomas.

ABSTRACT: Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKNs, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse-enriched training set. Using a complete case analysis (n = 182), including 91 with CNS relapse, we applied a least absolute shrinkage and selection operator Cox regression model to select weighted clinicopathologic variables for the CITI score, which we validated in an external cohort from the Swedish Lymphoma Registry (n = 566). CNS relapse was most frequently observed in patients with peripheral T-cell lymphoma, not otherwise specified (25%). Median time to CNS relapse and median overall survival after CNS relapse were 8.0 and 4.7 months, respectively. We calculated unique CITI risk scores for individual training set patients and stratified them into risk terciles. Validation set patients with low-risk (n = 158) and high-risk (n = 188) CITI scores had a 10-year cumulative risk of CNS relapse of 2.2% and 13.4%, respectively (hazard ratio, 5.24; 95% confidence interval, 1.50-18.26; P = .018). We developed an open-access web-based CITI calculator (https://redcap.link/citicalc) to provide an easy tool for clinical practice. The CITI score is a validated model to predict patients with MTNKN at the highest risk of developing CNS relapse.

Studying crystallisation processes using electron microscopy: The importance of sample preparation.

We present a comparison of common electron microscopy sample preparation methods for studying crystallisation processes from solution using both scanning and transmission electron microscopy (SEM and TEM). We focus on two widely studied inorganic systems: calcium sulphate, gypsum (CaSO4·2H2O) and calcium carbonate (CaCO3). We find significant differences in crystallisation kinetics and polymorph selection between the different sample preparation methods, which indicate that drying and chemical quenching can induce severe artefacts that are capable of masking the true native state of the crystallising solution. Overall, these results highlight the importance of cryogenic (cryo)-quenching crystallising solutions and the use of full cryo-TEM as the most reliable method for studying the early stages of crystallisation.

A Hollow TFG Condensate Spatially Compartmentalizes the Early Secretory Pathway.

In the early secretory pathway, endoplasmic reticulum (ER) and Golgi membranes form a nearly spherical interface. In this ribosome-excluding zone, bidirectional transport of cargo coincides with a spatial segregation of anterograde and retrograde carriers by an unknown mechanism. We show that at physiological conditions, Trk-fused gene (TFG) self-organizes to form a hollow, anisotropic condensate that matches the dimensions of the ER-Golgi interface. Regularly spaced hydrophobic residues in TFG control the condensation mechanism and result in a porous condensate surface. We find that TFG condensates act as a molecular sieve, enabling molecules corresponding to the size of anterograde coats (COPII) to access the condensate interior while restricting retrograde coats (COPI). We propose that a hollow TFG condensate structures the ER-Golgi interface to create a diffusion-limited space for bidirectional transport. We further propose that TFG condensates optimize membrane flux by insulating secretory carriers in their lumen from retrograde carriers outside TFG cages.

Perimenopausal physical activity and dementia risk: A systematic review.

Mixed-gender studies predominate the current literature exploring the interaction between physical activity and dementia risk. Considering that menopause appears to contribute to females' increased risk of cognitive decline when compared to males, further clarity is required on the impact of physical activity in reducing late-life dementia risk specifically in perimenopausal females. A literature search of MEDLINE, EMBASE, Web of Science, SCOPUS and CINAHL databases yielded fourteen studies for review. A significant inverse relationship between perimenopausal leisure time physical activity, or physical fitness, and future all-cause dementia risk was found in most studies exploring this interaction. Higher levels of perimenopausal household physical activity and combined non-leisure time physical activity also displayed a favourable impact in lowering dementia risk. A dose-response effect was demonstrated, with approximately 10 MET-hour/week of leisure time physical activity required for significant dementia risk reduction. Three of four papers exploring causality provided analyses that are proposed to counter the 'reverse causation' argument, suggesting that physical activity may indeed have a protective role in reducing dementia risk post-menopause. The current systematic review provides promising results regarding the impact of pre- and perimenopausal physical activity on reducing late-life dementia risk, suggesting that promoting perimenopausal physical activity may serve as a crucial tool in mitigating the risk of post-menopausal cognitive decline.

Guía de práctica clínica sobre el manejo del schwannoma vestibular / Clinical practice guideline on the management of vestibular schwannoma

Introducción: El schwannoma vestibular (SV) es el tumor más frecuente del ángulo pontocerebeloso. La mayor accesibilidad a las pruebas radiológicas ha incrementado su diagnóstico. Teniendo en cuenta las características del tumor, la clínica y la edad del paciente se han propuesto tres estrategias terapéuticas, observación, cirugía o radioterapia. La elección de la más adecuada para cada paciente es un motivo de controversia frecuente. Material y métodos: El presente trabajo incluye una revisión exhaustiva sobre cuestiones relativas al SV que pueden servir de guía clínica en el manejo de pacientes con estas lesiones. La presentación se ha orientado en forma de preguntas que el clínico se hace habitualmente y las respuestas están redactadas y/o revisadas por un panel de expertos nacionales e internacionales consultados por la Comisión de Otología de la SEORL-CCC. Resultados: Se ha elaborado un listado con los 13 bloques temáticos más controvertidos sobre el manejo del SV en forma de 50 preguntas y se han buscado las respuestas a todas ellas mediante una revisión sistemática de la literatura (artículos publicados en PubMed y Cochrane Library entre 1992 y 2023 sobre cada bloque temático). Treinta y tres expertos, liderados por la Comisión de Otología de la SEORL-CCC, han analizado y discutido todas las respuestas. En el Anexo 1 pueden encontrarse 14 preguntas adicionales divididas en cuatro bloques temáticos. Conclusiones: Esta guía de práctica clínica sobre el manejo del SV ofrece respuestas consensuadas a las preguntas más habituales que se plantean sobre este tumor. La ausencia de suficientes estudios prospectivos hace que los niveles de evidencia sobre el tema sean en general medios o bajos. Este hecho incrementa el interés de este tipo de guías de práctica clínica elaboradas por expertos.(AU)

IntroductionVestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle. The greater accessibility to radiological tests has increased its diagnosis. Taking into account the characteristics of the tumour, the symptoms and the age of the patient, three therapeutic strategies have been proposed: observation, surgery or radiotherapy. Choosing the most appropriate for each patient is a frequent source of controversy. Material and methods: This paper includes an exhaustive literature review of issues related to VS that can serve as a clinical guide in the management of patients with these lesions. The presentation has been oriented in the form of questions that the clinician usually asks himself and the answers have been written and/or reviewed by a panel of national and international experts consulted by the Otology Commission of the SEORL-CCC. Results: A list has been compiled containing the 13 most controversial thematic blocks on the management of VS in the form of 50 questions, and answers to all of them have been sought through a systematic literature review (articles published on PubMed and Cochrane Library between 1992 and 2023 related to each thematic area). Thirty-three experts, led by the Otology Committee of SEORL-CCC, have analyzed and discussed all the answers. In Annex 1, 14 additional questions divided into 4 thematic areas can be found. Conclusions: This clinical practice guideline on the management of VS offers agreed answers to the most common questions that are asked about this tumour. The absence of sufficient prospective studies means that the levels of evidence on the subject are generally medium or low. This fact increases the interest of this type of clinical practice guidelines prepared by experts.(AU)

Long or complicated mpox in patients with uncontrolled HIV infection.

To date, former research about the impact of HIV infection on mpox poor outcomes is still limited and controversial. Therefore, the aim of this study was to assess the impact of HIV on the clinical course of mpox, in a large population of patients from Spain. Nationwide case-series study. Patients from 18 Spanish hospitals, with PCR-confirmed mpox from April 27, 2022 to June 30, 2023 were included in this study. The main outcome was the development of long or complicated (LC) mpox, defined as: (i) duration of the clinical course ≥ 28 days, or; (ii) disseminated disease, or: (iii) emergence of severe complications. One thousand eight hundred twenty-three individuals were included. Seven hundred eighty-six (43%) were people living with HIV (PLWH), of whom 11 (1%) had a CD4 cell count < 200 cells/mm3 and 33 (3%) <350 cells/mm3 . HIV viral load ≥ 1000 cp/mL was found in 27 (3%) PLWH, none of them were on effective ART. Fifteen (60%) PLWH with HIV-RNA ≥ 1000 cp/mL showed LC versus 182 (29%) PLWH with plasma HIV-RNA load < 1000 copies/mL and 192 (24%) individuals without HIV infection (p < 0.001). In multivariate analysis, adjusted by age, sex, CD4 cell counts and HIV viral load at the time of mpox, only plasma HIV-RNA ≥ 1000 cp/mL was associated with a greater risk of developing LC mpox [adjusted OR = 4.06 (95% confidence interval 1.57-10.51), p = 0.004]. PLWH with uncontrolled HIV infection, due to lack of ART, are at a greater risk of developing LC mpox. Efforts should be made to ensure HIV testing is carried out in patients with mpox and to start ART without delay in those tested positive.

Clinical practice guideline on the management of vestibular schwannoma.

INTRODUCTION: Vestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle. The greater accessibility to radiological tests has increased its diagnosis. Taking into account the characteristics of the tumour, the symptoms and the age of the patient, three therapeutic strategies have been proposed: observation, surgery or radiotherapy. Choosing the most appropriate for each patient is a frequent source of controversy. MATERIAL AND METHODS: This paper includes an exhaustive literature review of issues related to VS that can serve as a clinical guide in the management of patients with these lesions. The presentation has been oriented in the form of questions that the clinician usually asks himself and the answers have been written and/or reviewed by a panel of national and international experts consulted by the Otology Commission of the SEORL-CCC. RESULTS: A list has been compiled containing the 13 most controversial thematic blocks on the management of VS in the form of 50 questions, and answers to all of them have been sought through a systematic literature review (articles published on PubMed and Cochrane Library between 1992 and 2023 related to each thematic area). Thirty-three experts, led by the Otology Committee of SEORL-CCC, have analyzed and discussed all the answers. In Annex 1, 14 additional questions divided into 4 thematic areas can be found. CONCLUSIONS: This clinical practice guideline on the management of VS offers agreed answers to the most common questions that are asked about this tumour. The absence of sufficient prospective studies means that the levels of evidence on the subject are generally medium or low. This fact increases the interest of this type of clinical practice guidelines prepared by experts.

Zinner's Syndrome and Retroperitoneal Fibrosis: An Unknown Association.

We report the case of a 24-year-old male presenting with obstructive renal failure, characterised by imaging evidence of a cystic lesion contingent upon the seminal vesicle and concurrent renal agenesis. Initial management involved urinary diversion, followed by outpatient monitoring and subsequent recurrence. Subsequent diagnostic assessments led to the identification of Zinner's syndrome, accompanied by retroperitoneal fibrosis. We present the clinical course, diagnostic methodology and the efficacious implementation of medical-surgical therapeutic interventions, yielding favourable outcomes. LEARNING POINTS: The value of the Internal Medicine team in the assessment of low prevalence diseases.The importance of multidisciplinary teams.Integration of the internists in the surgical teams.

C≡N and N≡O Bond Cleavages of Acetonitrile and Nitrosyl Ligands at a Dimolybdenum Center to Render Ethylidyne and Acetamidinate Ligands.

Extended reduction of [Mo2Cp2(µ-Cl)(µ-PtBu2)(NO)2] (1) with Na(Hg) in acetonitrile (MeCN) at room temperature resulted in an unprecedented full cleavage of the C≡N bond of a coordinated MeCN molecule to yield the vinylidene derivative Na[Mo2Cp2(µ-PtBu2)(µ-CCH2)(NO)2], which upon protonation with (NH4)PF6 gave the ethylidyne complex [Mo2Cp2(µ-PtBu2)(µ-CMe)(NO)2] [Mo1-Mo2 = 2.9218(2) Å] in a selective and reversible way. Controlled reduction of 1 at 273 K yielded instead, after protonation, the 30-electron acetamidinate complex [Mo2Cp2(µ-PtBu2)(µ-κN:κN'-HNCMeNH)(µ-NO)]PF6 [Mo1-Mo2 = 2.603(2) Å], in a process thought to stem from the paramagnetic MeCN-bridged intermediate [Mo2Cp2(µ-PtBu2)(µ-NCMe)(NO)2], followed by a complex sequence of elementary steps including cleavage of the N≡O bond of a nitrosyl ligand.

Postoperative Psychological Predictors for Chronic Postsurgical Pain After a Knee Arthroplasty: A Prospective Observational Study.

OBJECTIVE: Chronic postsurgical pain (CPSP) is a significant adverse effect shown in around 20% of people who had undergone a knee arthroplasty (KA). Psychological risk factors have emerged as significant and potentially modifiable risk factors for its development. However, there is still little evidence when assessing these factors during the acute postoperative period. This study aimed to assess the predictive value of postoperative pain catastrophizing, pain-related fear of movement, anxiety, depression, and pain attitudes in developing CPSP after KA. METHODS: A 6-month follow-up prospective observational study design was used. The study sample comprised 115 people who underwent a KA due to painful primary osteoarthritis. Measures of pain catastrophizing, pain-related fear of movement, anxiety, depression, and pain attitudes were obtained 1 week after surgery. CPSP was set at an intensity of ≥30 using a 100-mm visual analog scale at 3 and 6 months after surgery. RESULTS: Analysis revealed that baseline pain intensity, pain catastrophizing, pain-related fear of movement, anxiety, depression, and maladaptive pain attitudes were significant predictors of chronic pain at 3 and 6 months after surgery in a univariate analysis. However, at 3 months after surgery, only pain intensity and pain catastrophizing were predictors in the final multivariate model forecasting disturbing pain. Moreover, 6 months after surgery, pain intensity and distrust in medical procedures remained independent predictors. Most of the psychological factors can be grouped into a single dimension defined as pain-related psychological distress. CONCLUSION: The results suggest that postoperative pain intensity, pain catastrophizing, and pain attitudes are independent predictors for CPSP after KA. IMPACT: Postoperative cognitive and emotional factors should be considered alongside pain intensity during postoperative rehabilitation after KA because they could influence the development of CPSP.