JAK inhibitors in refractory dermatomyositis: A case series.

This retrospective cohort study assessed the efficacy and safety of Janus kinase (JAK) inhibitors, tofacitinib and baricitinib, in 14 patients with refractory dermatomyositis (DM), a multisystemic autoimmune disorder with limited therapeutic options. Results demonstrated a significant median decrease of 21 points and a 76% reduction in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scores, along with a complete resolution of muscular symptoms in 64% of the patients. JAK inhibitors were effective in managing refractory DM across various subtypes with mild and manageable adverse events.

Prader-Willi syndrome in a large sample from Spain: general features, obesity and regular use of psychotropic medication.

BACKGROUND: Prader-Willi syndrome (PWS), a genetically determined disorder, the most frequent cause of early onset obesity, is associated with physical and cognitive dysfunctions and behavioural disturbances; these disturbances are frequently treated with psychotropic medication. The aim of this cross-sectional study was to describe the characteristics of the first large national sample of persons with PWS in Spain and analyse the relationships of those characteristics with key demographic and clinical factors, particularly with obesity and the regular use of psychotropic medication. METHODS: Participants were recruited among all members of the Spanish Prader-Willi Association who agreed to take part in the study and fulfilled its inclusion criteria. Family and patient demographic features, family size and birth order, intelligence quotient (IQ), anthropometric measures, lifestyle habits, behavioural disturbances (with the Aberrant Behavior Checklist) and clinical data, as well as use of psychotropic drugs and their side effects (with the UKU scale), were collected in genetically confirmed cases of PWS. Bivariate and logistic regression analyses were used for determining the associations of demographic and clinical factors with both obesity and the regular use of psychotropic medication. RESULTS: The cohort included 177 participants (aged 6-48 years), that is, 90 (50.8%) males and 87 (49.2%) females. Behavioural disturbances were present in a range of 75% to 93% of participants; psychotropic medication was prescribed to 81 (45.8%) of them. Number of siblings showed a direct correlation with IQ, especially among males, and inappropriate speech was more intense in only-child females. Obesity was, in parallel, strongly associated with ascending age and with not being currently under growth hormone (GH) treatment. Participants taking any psychotropic medication were characterised by more frequent age ≥30 years, high level of hyperactivity and a psychiatric diagnosis. CONCLUSIONS: Characterisation of persons with PWS in Spain confirms their physical and behavioural phenotype and supports the long-term application of GH therapy and the rational use of psychotropic medication.

Interaction among health workers and trans men: Findings from a qualitative study in Chile.

PURPOSE: To explore trans men's access and use of healthcare services in Chile, based on the experiences of the trans men themselves, as well as of healthcare professionals. METHODS: A qualitative study with an ethnographic approach was carried out with 30 participants: 14 trans men and 16 healthcare professionals. Semi-structured one-on-one interviews with open-ended questions were used to collect the data. A thematic analysis was carried out with the NVivo Software. RESULTS: Three main themes were identified: (1) failures in the recognition of trans identity, (2) challenges with patient-centered care, and (3) use of other ("non-trans") health services. CONCLUSIONS: The results suggest that not all transition processes are the same, individuals seek different ways; therefore, it is necessary to consider different body types and identities when planning programs and care for men in transition. Moreover, the accompaniment provided during the gender transition process should contemplate emotional and mental support. CLINICAL RELEVANCE: The study outlines the need for all healthcare professionals to have training and knowledge about the transgender population, regardless of whether they are part of the teams supporting gender transition processes. The role of nurses and the contributions that can be made from nursing discipline in this research field are fundamental.

Quality of life and functional outcomes in tongue cancer patients: a long-term, prospective, comparative study.

BACKGROUND: The tongue has an indispensable role in communication, swallowing and breathing. Tongue cancer treatment involves direct resection of the tumor and surrounding tissue, which can limit many essential functions of the tongue. There are few patient-reported quality of life studies involving tongue cancer exclusively. There is also a lack of data on the outcomes of quality of life regarding different reconstructive methods, adjuvant non-surgical therapies and other predicting factors. Our objective is to assess the quality of life, functional status, and predicting factors in patients with tongue cancer up to one year after surgical resection. MATERIAL AND METHODS: Thirty-six patients with tongue cancer were prospectively identified between October of 2017 and January 2021. Patients were examined before and one, three, six and twelve months after surgical resection with the validated University of Washington Quality of Life questionnaire (UW-QOL). Data collection included patient age, sex, TNM staging, size of resection, neck dissection, tracheostomy, reconstructive method and adjuvant therapies. Outcome scores were compared using the Friedman test. Multiple linear regression analysis was used to identify the predictors of quality of life and functional status. RESULTS: The use of UWQOL scores as dependent variables revealed the following predicting factors: age, tobacco use, radiotherapy, chemotherapy, reconstruction method and neck dissection. CONCLUSIONS: The most relevant findings in our study are that flap reconstruction becomes increasingly necessary when a glossectomy resection is over 45 mm, in order to maintain tongue function. We established that the reconstructive flap type does not influence quality of life in the long term. Also, we have found that cervical sentinel node biopsy provides better quality of life over neck dissection in the first 3 months after surgery.

Reflectance Confocal Microscopy Terminology in Spanish: A Delphi Consensus Study. / Consenso de terminología en microscopia confocal de reflectancia en español mediante método Delphi.

The terminology used to describe reflectance confocal microscopy (RCM) findings in both melanocytic and nonmelanocytic lesions has been standardized in English. We convened a panel of Spanish-speaking RCM experts and used the Delphi method to seek consensus on which Spanish terms best describe RCM findings in this setting. The experts agreed on 52 terms: 28 for melanocytic lesions and 24 for nonmelanocytic lesions. The resulting terminology will facilitate homogenization, leading to a better understanding of structures, more standardized descriptions in clinical registries, and easier interpretation of clinical reports exchanged between dermatologists.

Bypassing the Need for Cell Permeabilization: Nanobody CDR3 Peptide Improves Binding on Living Bacteria.

Membrane interaction constitutes to be an essential parameter in the mode of action of entities such as proteins, as well as cell-penetrating and antimicrobial peptides, resulting in noninvasive or lytic activities depending on the membrane compositions and interactions. Recently, a nanobody able to interact with the top priority, multidrug-resistant bacterial pathogen Acinetobacter baumannii was discovered, although binding took place with fixed cells only. To potentially overcome this limitation, linear peptides corresponding to the complementarity-determining regions (CDR) were synthesized and fluorescently labeled. Microscopy data indicated clear membrane interactions of the CDR3 sequence with living A. baumannii cells, indicating both the importance of the CDR3 as part of the parent nanobody paratope and the improved binding ability and thus avoiding the need for permeabilization of the cells. In addition, cyclization of the peptide with an additionally introduced rigidifying 1,2,3-triazole bridge retains its binding ability while proteolytically protecting the peptide. Overall, this study resulted in the discovery of novel peptides binding a multidrug-resistant pathogen.

Evaluation of the effectiveness and safety of combined oral and topical photoprotection with a standardized extract of Polypodium leucotomos (Fernblock®) in a Moroccan population with xeroderma pigmentosum.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare autosomal-recessive genodermatosis resulting from a DNA-repair defect syndrome. The purpose was to evaluate the prevention on new malignant lesions in patients taking a supplement with Fernblock® (Polypodium leucotomos extract [PLE]) and secondarily correlation with the photoprotective behavior. METHODS: A prospective, single-center and open cohort study was conducted over a 12-month period. The study was performed in Morocco. Optimal photoprotection behavior was recommended. Patients were instructed to take one capsule containing 480 mg of Fernblock® and 5 mcg vitamin D and to apply sunscreen with a SPF50+ and Fernblock® every 2 h during sun exposure. The demographic, clinical, and dermatoscopic patient data were collected at baseline (T0) and following visits at 3 months (T3), 6 months (T6), and 12 months (T12) when it was assessed: Investigator Global Assessment (IGA), Patient/Guardian Global Assessment (PGA), Patient/Guardian Satisfaction Questionnaire, and Photographic and Adverse Events Registration. Pertinent statistical study was performed. RESULTS: Eighteen patients completed the study. Eleven patients (61%) finished the study without new lesions. Seven patients developed new lesions by the end of the study. Among them, only 30% showed an ideal photoprotective behavior. The lack of an optimal photoprotective behavior increased the probability of developing lesions by 2.5 times with 95% confidence interval. CONCLUSIONS: In our study, more than 60% of patients taking a supplement with Fernblock® did not develop new lesions, and furthermore, we detected that patients following almost ideal photoprotection were 2.5 times less likely to develop NMSC lesions.

[Prone positioning in Covid-19 patients with acute respiratory distress syndrome and invasive mechanical ventilation]. / Decúbito prono en pacientes COVID-19 con síndrome de distrés respiratorio agudo y ventilación mecánica invasiva.

Objective: To identify adverse events related to prone positioning in COVID-19 patients with severe disease and acute respiratory distress syndrome, to analyze the risk factors associated with the development of anterior pressure ulcers, to determine whether the recommendation of prone positioning is associated with improved clinical outcomes. Methods: Retrospective study performed in 63 consecutive patients with COVID-19 pneumonia admitted to intensive care unit on invasive mechanical ventilation and treated with prone positioning between March and April 2020. Association between prone-related pressure ulcers and selected variables was explored by the means of logistic regression. Results: A total of 139 proning cycles were performed. The mean number of cycles were 2 [1-3] and the mean duration per cycle was of 22 hours [15-24]. The prevalence of adverse events this population was 84.9%, being the physiologic ones (i.e., hypo/hypertension) the most prevalent. 29 out of 63 patients (46%) developed prone-related pressure ulcers. The risk factors for prone-related pressure ulcers were older age, hypertension, levels of pre-albumin < 21 mg/dL, the number of proning cycles and severe disease. We observed a significant increase in the PaO2/FiO2 at different time points during the prone positioning, and a significant decrease after it. Conclusions: There is a high incidence of adverse events due to PD, with the physiological type being the most frequent. The identification of the main risk factors for the development of prone-related pressure ulcers will help to prevent the occurrence of these lesions during the prone positioning. Prone positioning offered an improvement in the oxygenation in these patients.

Low serum osteocalcin levels are associated with diabetes mellitus in glucocorticoid treated patients.

Bone turnover markers are decreased in GC-treated subjects with DM. Decreased OC levels in GC-treated patients were associated with an increased risk of DM. These results suggest the involvement of OC in glucose homeostasis regulation in DM. INTRODUCTION: Osteocalcin (OC) is involved in the regulation of glucose homeostasis. Glucocorticoid (GC) treatment is associated with impaired osteoblast function, decreased OC levels, and the development and/or worsening of pre-existing diabetes mellitus (DM). Whether decreased OC levels in GC-treated subjects contribute to DM is not well known. The aim of this study was to analyse whether OC levels in GC-treated patients are associated with the presence of DM. METHODS: One hundred twenty-seven patients (aged 61.5 ± 17.9 years) on GC treatment were included. GC dose, treatment duration, presence of DM and bone formation (OC, bone ALP, PINP) and resorption markers (urinary NTX, serum CTX) were analysed. The cut-offs of each bone turnover marker (BTM) for the presence of DM were evaluated and optimised with the Youden index and included in the logistic regression analysis. RESULTS: Among the patients, 17.3% presented DM. No differences were observed in GC dose or duration or the presence of fractures. Diabetics showed lower levels of OC (7.57 ± 1.01 vs. 11.56 ± 1; p < 0.001), PINP (21.48 ± 1.01 vs. 28.39 ± 1; p = 0.0048), NTX (24.91 ± 1.01 vs. 31.7 ± 1; p = 0.036) and CTX (0.2 ± 1.01 vs. 0.3 ± 1; p = 0.0016). The discriminating BTM cut-offs for DM presence were < 9.25 ng/mL for OC, < 24 ng/mL for PINP, < 27.5 nMol/mM for NTX and < 0.25 ng/mL for CTX. In a multivariate logistic regression model adjusted for GC dose, BMI, age and the above four BTMs, only OC remained independently associated with DM presence. Thus, in a model adjusted for GC dose, BMI and age, OC was significantly associated with DM (OR: 6.1; 95%CI 1.87-19.89; p = 0.001). CONCLUSION: Decreased OC levels in GC-treated patients are associated with increased odds of DM, and only OC was independently associated with DM in a model including four BTMs.

In Vivo reflectance confocal microscopy of cutaneous acute graft-versus-host disease: concordance with histopathology and interobserver reproducibility of a glossary with representative images.

BACKGROUND: The reliability to non-invasively identify features of inflammatory dermatoses by reflectance confocal microscopy (RCM) remains unknown. Lack of formal training among RCM readers can result in inconsistent assessments, limiting clinical utility. Specific consensus terminology with representative images is necessary to ensure consistent feature-level interpretation among RCM readers. OBJECTIVES: (1) Develop a glossary with representative images of RCM features of cutaneous acute graft-versus-host disease (aGVHD) for consistent interpretation among observers, (2) assess the interobserver reproducibility among RCM readers using the glossary, and (3) determine the concordance between RCM and histopathology for aGVHD features. METHODS: Through an iterative process of refinement and discussion among five international RCM experts, we developed a glossary with representative images of RCM features of aGVHD. From April to November 2018, patients suspected of aGVHD were imaged with RCM and subsequently biopsied. 17 lesions from 12 patients had clinically and pathologically confirmed cutaneous aGVHD. For each of these lesions, four dermatopathologists and four RCM readers independently evaluated the presence of aGVHD features in scanned histopathology slides and 1.5 × 1.5 mm RCM submosaics at 4 depths (blockstacks) respectively. RCM cases were adjudicated by a fifth RCM expert. Interobserver reproducibility was calculated by mean pairwise difference (U statistic). Concordance between modalities was determined by fraction of assignments with agreement. RESULTS: We present a glossary with representative images of 18 aGVHD features by RCM. The average interobserver reproducibility among RCM readers (75%, confidence interval, CI: 71-79%) did not differ significantly from dermatopathologists (80%, 76-85%). The concordance between RCM and histopathology was 59%. CONCLUSIONS: By using the glossary, the interobserver reproducibility among RCM readers was similar to the interobserver reproducibility among dermatopathologists. There was reasonable concordance between RCM and histopathology to visualize aGVHD features. The implementation of RCM can now be advanced in a variety of inflammatory conditions with a validated glossary and representative image set.

Food industrial biowaste-based magnetic activated carbons as sustainable adsorbents for anthropogenic mercury emissions.

Bio-derived magnetic activated carbons from industrial chestnut shell waste have been obtained through a novel, optimized and sustainable methodology where impregnation, pyrolysis, acid washing or other intermediate steps commonly used in the activation process were eliminated saving time, energy and costs. The resulting materials (MACs) were obtained at 220-800 °C showed interesting properties: textural (SBET up to 568 m2 g-1) and magnetic (different iron species developed), depending on the activation temperature employed. Data showed outstanding results when MACs were tested for Hg removal in pollution emissions at 150 °C in lab-scale device. In MACs obtained at 500-600 °C, where the highest concentration of magnetite was found, the best Hg adsorption capacity was achieved, while it decreased when metallic iron or iron carbides were present (MACs obtained at 800 °C). Moreover, the difference of Hg0 removal/adsorption in N2+O2 and Simulated Flue Gas atmosphere between MACs obtained at 500 and 600 °C pointed out the influence on Hg removal of additional parameters, as surface chemistry and the existence of sulfur or chloride. The determination of Hg species in post-retention solids confirmed the mercury oxidation by high-valence iron ions (Fe3+) and the involvement of physisorption and chemisorption processes for the gas-solid interaction mechanism.

Destructive strategies in treating cerebrovascular pathology: Review and treatment algorithm.

The goal of cerebrovascular pathology treatment is most often to angiographically eradicate a lesion with the lowest probability of morbidity. Destructive strategies using parent vessel occlusion are less commonly considered in the modern era. We review principles of parent vessel occlusion for treatment of cerebrovascular pathology and select cases to demonstrate these principles. Many common cerebrovascular conditions have been safely and effectively treated with destructive strategies including intracranial aneurysms, traumatic craniocervical vascular injuries, and oncologic indications such as carotid blowout. Avoiding procedural morbidity in these procedures involves assessment of collaterals distal to a planned parent vessel occlusion, determination of this arterial segment's eloquence, prevention of distal migration of endovascular devices or thrombus, and prevention of stump emboli. An algorithm for case selection and method of destructive technique versus a reconstructive approach can be used. Destructive strategies for treating cerebrovascular pathology are still relevant and can be applied safely in appropriately selected cases.

Extracellular matrix remodelling is associated with muscle force increase in overloaded mouse plantaris muscle.

AIMS: Transforming growth factor-ß (TGF-ß) signalling is thought to contribute to the remodelling of extracellular matrix (ECM) of skeletal muscle and to functional decline in patients with muscular dystrophies. We wanted to determine the role of TGF-ß-induced ECM remodelling in dystrophic muscle. METHODS: We experimentally induced the pathological hallmarks of severe muscular dystrophy by mechanically overloading the plantaris muscle in mice. Furthermore, we determined the role of TGF-ß signalling on dystrophic tissue modulation and on muscle function by (i) overloading myostatin knockout (Mstn-/- ) mice and (ii) by additional pharmacological TGF-ß inhibition via halofuginone. RESULTS: Transcriptome analysis of overloaded muscles revealed upregulation predominantly of genes associated with ECM, inflammation and metalloproteinase activity. Histology revealed in wild-type mice signs of severe muscular dystrophy including myofibres with large variation in size and internalized myonuclei, as well as increased ECM deposition. At the same time, muscle weight had increased by 208% and muscle force by 234%. Myostatin deficiency blunted the effect of overload on muscle mass (59% increase) and force (76% increase), while having no effect on ECM deposition. Concomitant treatment with halofuginone blunted overload-induced muscle hypertrophy and muscle force increase, while reducing ECM deposition and increasing myofibre size. CONCLUSIONS: ECM remodelling is associated with an increase in muscle mass and force in overload-modelled dystrophic muscle. Lack of myostatin is not advantageous and inhibition of ECM deposition by halofuginone is disadvantageous for muscle plasticity in response to stimuli that induce dystrophic muscle.

Functional redundancy and compensation: Deletion of multiple murine Crisp genes reveals their essential role for male fertility.

Mammalian Cysteine-RIch Secretory Protein (CRISP) family includes four members present in sperm and reported to regulate Ca2+ channels and fertilization. Based on our previous observations using single knockouts models and suggesting the existence of functional compensation among CRISP proteins, we investigated their relevance for male fertility by generating multiple Crisp gene mutants by CRISPR/Cas9 technology. Whereas targeting of Crisp1 and Crisp3 yielded subfertile males with early embryo developmental defects, the same deletion in zygotes from fertile Crisp2-/- .Crisp4-/- mice led to the generation of both triple and quadruple knockout mice exhibiting a complete or severe disruption of male fertility due to a combination of sperm transport, fertilization, and embryo developmental defects linked to intracellular Ca2+ dysregulation. These observations reveal that CRISP proteins are essential for male fertility and organize in functional modules that contribute distinctly to fertility success, bringing insights into the mechanisms underlying functional redundancy/compensation in protein families and emphasizing the importance of generating multiple and not just single knockout which might be masking the true functional relevance of family genes.

Expression of mBD4, mBD3 and CRAMP during type II collagen-induced arthritis/CIA and their association with inflammation and bone-remodeling markers.

The aim of this study was to analyze the expression of mBD4, mBD3 and CRAMP in joint of mice with type II collagen-induced arthritis/CIA and to explore its possible association with IL-10, IL-4, IFN-γ, IL-17, MMP3, RANK/RANKL/OPG and histological parameters. METHODS: CIA was induced in 44 DBA/1 J mice. The joints from mice were classified into the onset, peak and remission phase of CIA. Histological sections were stained with hematoxylin-eosin and safranin O. The expression of CRAMP, mBD-3, mBD-4, and MMP-3 was evaluated using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. The expression of IL-10, IL-4, IFN-γ, IL-17, RANK/RANKL/OPG was analyzed by RT-PCR. RESULTS: We observed that inflammation and immunostained cells for CRAMP increased in the peak and remission phases compared to the control group. In addition, increments in relative expressions of CRAMP were detected for the remission phase and in IL-4 and IL-17 in the peak phase compared to the control and onset phase. In addition, an increase in IL-10 in a peak phase compared to the control, as well as the relative expression of IFN-γ in remission phase was higher than in the onset phase. This was accompanied by an increase in cartilage damage in the peak phase compared to the control. Cells immunostained to MMP3 increased in the peak phase compared to the onset and control group, and relative expression of MMP3 was detected in the peak phase compared to the onset, remission, and control group. We observed that the relative expression of RANK and RANKL in the peak phase was higher than in control and onset phase. Finally, the relative expression of OPG in the peak phase compared to the onset, remission, and control group was detected. Regarding CRAMP behavior in the different phases studied, it was positively correlated with IL-4 and RANK, and showed a negative correlation with IFN-γ, IL-17, IL-10, RANKL, OPG and RANKL/OPG ratio in the control group. Also was positively correlated with IFN-γ, IL-17, IL-4, IL-10, as well as with RANK, RANKL, and OPG in the onset and peak phases of the CIA. In the peak phase, CRAMP showed a positive association with MMP3, and we observed a direct correlation between CRAMP and IFN-γ and RANKL/OPG ratio in remission phase. mBD3 correlates positively with IFN-γ, IL-17, IL-10, RANKL, OPG and RANKL/OPG ratio, and showed a negative correlation with CRAMP, MMP3, and RANK in the control group. Also, it was directly associated with IFN-γ, IL-17, IL-4, IL-10 and RANKL in the onset phase while it was inversely associated with CRAMP, MMP-3, RANK, RANKL, and OPG in the peak phase. Finally, mBD3 was inversely correlated with MMP3 in the remission phase and was directly associated with CRAMP, IFN-γ and RANKL/OPG ratio in this phase. mBD4 was directly associated with CRAMP, IFN-γ, IL-17, IL-4, IL-10, RANKL / OPG in the onset phase, and with CRAMP, IFN-γ, IL-17, IL-4, IL-10, MMP3, RANK, RANKL and OPG in the peak phase. Finally, mBD4 was positively associated with mBD3, IFN-γ, IL-17, IL-10, RANK, RANKL OPG and RANKL/OPG in the CIA remission phase. CONCLUSIONS: Our results demonstrate that CRAMP plays an important role in CIA progress and suggest that its abundance is associated with local pro- and anti-inflammatory status. This makes us propose CRAMP as a possible contributor of bone reconstruction in the last stage of CIA.

CT findings of pulmonary cysts.

Pulmonary cysts are thin-walled radiolucent lesions that may appear in a variety of uncommon disorders known as diffuse cystic lung diseases (DCLD) that essentially includes lymphangioleiomyomatosis (LAM), Langerhans cell histiocytosis (LCH), lymphocytic interstitial pneumonia (LIP), Pneumocystis jiroveci pneumonia (PJP), and Birt-Hogg-Dubé syndrome (BHDS). Moreover, they have been reported in several cases of coronavirus disease 2019 (COVID-19). The purpose of this review is to provide a practical approach for evaluating lung cysts when encountered on CT. We describe the imaging findings of DLCD emphasising their differences in terms of shape and distribution of the cysts, as well as their association with other findings such as nodules or ground-glass opacities, which may help in making a confident diagnosis. We also discuss the link between pulmonary cysts and COVID-19.

Azathioprine hypersensitivity syndrome: report of two cases with cutaneous manifestations.

Azathioprine is an immunosuppressant drug used in many dermatological and nondermatological pathologies. Azathioprine hypersensitivity syndrome (AHS) is a rare idiosyncratic reaction that is not related to dose or thiopurine methyltransferase activity. Up to half of cases of AHS can present with variable cutaneous manifestations besides fever, malaise and other systemic symptoms. It is important to be aware of AHS, as continuance or reintroduction of the drug can led to multiorgan failure and cardiovascular collapse.

Venous anomalies in hypoplastic posterior fossa: unsolved questions.

INTRODUCTION: Anomalous intracranial venous anatomy is described in patients with syndromic craniosynostosis and is of significant importance when it comes to surgical morbidity. However, it is still controversial its origin, type of circulation in each syndrome, how it behaves over time, when it can be interrupted and wether it needs to be studied. The purpose of this paper is to discuss these issues by reviewing the literature. METHODS: A literature search was performed using the PubMed database with a focus on papers including detailed descriptions of the venous outflow in complex and syndromic craniosynostosis. Search details used were the following: ("veins"[MeSH Terms] OR "veins"[All Fields] OR "venous"[All Fields]) AND ("abnormalities"[Subheading] OR "abnormalities"[All Fields] OR "anomalies"[All Fields]) AND syndromic[All Fields] AND ("craniosynostoses" [MeSH Terms] OR "craniosynostoses"[All Fields] OR "craniosynostosis"[All Fields]). Studies that exposed details of venous anomalies found in syndromic or complex craniosynostosis were selected. RESULTS: Of a total of 211 articles found, 11 were selected for this review. Of these, 5 were case reports, 5 retrospective studies, and only 1 prospective study. From the 6 series of cases presented, 5 discussed the relationship between jugular foramen stenosis (JFS) and collateral venous drainage. The authors discuss data from the literature for each leading question presented: 1-collateral circulation: is it an intrinsic trouble, a consequence of stenosis of the cranial base foramina or related to raised intracranial pressure (ICP)?; 2-what venous anomalies should we search for, and what is the best exam to study them?; 3-collateral circulation changes with time?; 4-can neurosurgeons interrupt the collateral circulation?; 5-should we study all complex types of craniosynostosis? CONCLUSION: The importance of the study of the venous outflow in patients with complex craniosynostosis is evident in the literature. The real relationship between intracranial hypertension, hypoplastic skull base foramen, Chiari I malformation, hydrocephalus, and venous collateral circulation remains unknown. Prospective studies focusing on molecular biology analysis will possibly solve all of these leading questions.

Clinicopathological factors associated with the presence of hypercapnia at admission in hospitalised cats with decompensated chronic kidney disease.

AIMS: To evaluate associations between clinicopathological variables and hypercapnia measured in cats with decompensated chronic kidney disease (CKD) on admission to a veterinary hospital. METHODS: This is a retrospective, cross-sectional study of cats (n = 39) that presented to a tertiary veterinary hospital in Argentina between June 2015 and December 2017 with blood creatinine concentrations >140 µmol/L, and abdominal ultrasound results consistent with CKD. Data recorded included venous partial pressure of CO2 (PvCO2), blood pH, haematocrit and concentrations of glucose, potassium, sodium, corrected sodium (Na+c), and ionised calcium in blood. A logistic regression model was used to assess associations between the presence of hypercapnia (PvCO2 ≥ 44.7 mmHg) and the other clinicopathologic variables. The duration of hospitalisation was compared in cats with and without hypercapnia using the Wilcoxon Rank Sum test. RESULTS: The final study population comprised 39 cats. Eleven cats (28.2%) had hypercapnia. In the logistic regression model, two independent variables were associated with the presence of hypercapnia at admission in cats with CKD: the concentration of creatinine in blood (OR = 1.06 (95% CI = 1.016-1.108); p = 0.007) and Na+c (OR = 1.33 (95% CI = 1.08-1.63); p = 0.005). There were no statistically significant differences in the length of hospital stay between the two groups. CONCLUSIONS AND CLINICAL RELEVANCE: There appears to be an association between elevated concentrations of creatinine and Na+c in blood, and hypercapnia in cats with CKD, suggesting careful assessment of blood gas and electrolyte parameters during hospitalisation is required. Further prospective studies are needed to evaluate the mechanisms behind this association and the association of hypercapnia with disease outcome including mortality.

A spontaneous missense mutation in the chromodomain helicase DNA-binding protein 8 (CHD8) gene: a novel association with congenital myasthenic syndrome.

AIMS: Congenital myasthenic syndromes (CMS) are characterized by muscle weakness, ptosis and episodic apnoea. Mutations affect integral protein components of the neuromuscular junction (NMJ). Here we searched for the genetic basis of CMS in female monozygotic twins. METHODS: We employed whole-exome sequencing for mutation detection and Sanger sequencing for segregation analysis. Immunohistology was done with antibodies against CHD8, rapsyn, ß-catenin (ßCAT) and golgin on fi-bro-blasts, human and mouse muscle. We recorded superresolution images of the NMJ using 3D-structured illumination microscopy. RESULTS: We discovered a spontaneous missense mutation in CHD8 [chr14:g.21,884,051G>A, GRCh37.p11 | c.1732C>T, NM_00117062 | p.(R578C)], the gene encoding chromodomain helicase DNA-binding protein 8. This is the first missense mutation affecting Duplin, the short 110 kDa isoform of CHD8. It is known that CHD8/Duplin negatively regulates ßCAT signalling in the WNT pathway and plays a role in chromatin remodelling. Inactivating CHD8 mutations are associated with autism spectrum disorder and intellectual disability in combination with facial dysmorphism, overgrowth and macrocephalus. No muscle-specific phenotype has been reported to date. Co-immunostaining with rapsyn on human and mouse muscle revealed a strong presence of CHD8 at the NMJ being located towards the sarcoplasmic side of the rapsyn cluster, where it co-localizes with ßCAT. CONCLUSION: We hypothesize CHD8 to have a role in the maintenance of the structural integrity and function of the NMJ. Both patients benefited from treatment with 3,4-diaminopyridine, a reversible blocker of voltage-gated potassium channels at the nerve terminal that prolongs the action potential and increases acetylcholine release.