Chest CT Scan Findings in Children with COVID-19: A Systematic Review.

Objectives: To gather, summarize, and appraise the available evidence on: 1) the accuracy of chest CT scan in diagnosing COVID-19 among children, and 2) the characteristic chest CT scan findings associated with COVID-19 pneumonia in children. Methods: We comprehensively searched databases (MEDLINE, COCHRANE), clinical trial registries, bibliographic lists of selected studies, and unpublished data for relevant studies. Guide questions from the Painless Evidence Based Medicine and the National Institutes of Health Quality Assessment Tools were used to assess study quality. Results: A poor quality study showed 86.0% (95% CI 73.8, 93.0) sensitivity and 75.9% (95% CI 67.1, 83.0) specificity of chest CT scan in diagnosing COVID-19 in children. Thirty-nine observational studies describing chest CT scan in children with COVID-19 showed abnormal findings in 717 of 1028 study subjects. Common chest CT scan findings in this population include: 1) ground glass opacities, patchy shadows, and consolidation, 2) lower lobe involvement, and 3) unilateral lung lesions. Conclusion: Studies which investigate the accuracy of chest CT scan in the diagnosis of COVID-19 in children are limited by heterogeneous populations and small sample sizes. While chest CT scan findings such as patchy shadows, ground glass opacities, and consolidation are common in children with COVID-19, these may be similar to the imaging findings of other respiratory viral illnesses.

Advances in Immunotherapy for Malignant Pleural Mesothelioma: From Emerging Strategies to Translational Insights.

MPM stands as a rare malignancy necessitating improved therapeutic strategies due to its limited treatment choices and unfavorable prognosis. The advent of immune checkpoint inhibitors has heralded a paradigm shift in the therapeutic landscape of MPM, offering promising avenues across diverse clinical scenarios. In the context of advanced stages of the disease, Immune check-point inhibitors targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-as-sociated protein 4 (CTLA-4), have exhibited encouraging potential in clinical trials, particularly manifesting efficacy among patients exhibiting disease progression following chemotherapy regimens. Innovative combination regimens, exemplified by the concurrent administration of nivolumab and ipilimumab, have demonstrated marked improvement in survival and patient's benefits. A deeper comprehension of the intricate genetic underpinnings of MPM, encompassing key mutations such as cyclin-dependent kinase inhibitor 2A (CDKN2A), neurofibromin 2 (NF2), and BRCA1-associated protein 1 (BAP1) mutations, has elucidated novel avenues for targeted therapeutic interventions. This review accentuates the transformative capacity of immunotherapy in revolutionizing the therapeutic outlook for MPM, thereby potentially translating into augmented survival rates and offering glimpses of new approaches on the horizon. Despite the persisting challenges, the synergistic crossroads of interdisciplinary research and collaborative clinical endeavors portend a hopeful landscape for MPM treatment.

El mesotelioma pleural maligno (MPM) es una neoplasia poco frecuente que requiere una mejora de las estrategias terapéuticas debido a sus limitadas opciones de tratamiento y a su pronóstico desfavorable. La llegada de los inhibidores de los puntos de control inmunitario ha supuesto un cambio de paradigma en el panorama terapéutico del MPM, ofreciendo vías prometedoras en diversos escenarios clínicos. En el contexto de los estadios avanzados de la enfermedad, los inhibidores de puntos de control inmunitario dirigidos contra la proteína de muerte celular programada 1 (PD-1) y la proteína 4 asociada a los linfocitos T citotóxicos (CTLA-4) han mostrado un potencial alentador en los ensayos clínicos, sobre todo por su eficacia en los pacientes con progresión de la enfermedad tras los regímenes de quimioterapia. Los regímenes combinados innovadores, ejemplificados por la administración concurrente de nivolumab e ipilimumab, han demostrado una mejora significativa de la supervivencia y de los beneficios para los pacientes. Una comprensión más profunda de los complejos fundamentos genéticos del MPM, que abarca mutaciones clave como el inhibidor de la cinasa dependiente de ciclina 2A (CDKN2A), la neurofibromina 2 (NF2) y las mutaciones de la proteína 1 asociada a BRCA1 (BAP1), ha dilucidado nuevas vías para el desarrollo de intervenciones terapéuticas dirigidas. Esta revisión acentúa la capacidad transformadora de la inmunoterapia para revolucionar las perspectivas terapéuticas en el MPM, lo que podría traducirse en un aumento de las tasas de supervivencia y ofrecer nuevos enfoques terapéuticos en el horizonte próximo. A pesar de los retos persistentes, el cruce sinérgico de la investigación interdisciplinar y los esfuerzos clínicos de colaboración auguran un panorama esperanzador en el tratamiento de los MPM.

Different mechanisms underlie compulsive alcohol self-administration in male and female rats.

BACKGROUND: Sex is an important factor in the progression and treatment of alcohol addiction, and therapeutic approaches may have to be tailored to potential sex differences. This highlights the importance of understanding sex differences in behaviors that reflect key elements of clinical alcohol addiction, such as continued use despite negative consequences ("compulsive use"). Studies in experimental animals can help provide an understanding of the role sex plays to influence these behaviors. METHODS: Large populations of genetically heterogeneous male and female Wistar rats were tested in an established model of compulsive alcohol self-administration, operationalized as alcohol responding despite contingent foot shock punishment. We also tested baseline (fixed ratio, unpunished) operant alcohol self-administration, motivation to self-administer alcohol (progressive ratio), and temporal discounting for alcohol reward. In search of predictors of compulsivity, animals were screened for novelty-induced place preference, anxiety-like behavior, pain sensitivity and corticosterone levels. The estrous cycle was monitored throughout the study. RESULTS: Unpunished self-administration of alcohol did not differ between males and females when alcohol intake was corrected for body weight. Overall, females showed higher levels of compulsive responding for alcohol. Compulsive response rates showed bimodal distributions in male but not in female rats when intermediate shock intensities were used (0.2 and 0.25 mA); at higher shock intensities, responding was uniformly suppressed in both males and females. We also found less steep discounting in females when alcohol was devalued by delaying its delivery. Males exhibited a stronger motivation to obtain alcohol under unpunished conditions, while females showed higher corticosterone levels at baseline. Factor analysis showed that an underlying dimension related to stress and pain predicted compulsivity in females, while compulsivity in males was predicted by a reward factor. We did not find differences in alcohol-related behaviors throughout the various stages of the estrous cycle. CONCLUSIONS: Our results suggest that mechanisms promoting compulsivity, a key feature of alcohol addiction, likely differ between males and females. This underscores the importance of considering sex as a biological variable in both preclinical and clinical research, and has potential treatment implications in alcohol addiction.

Sex plays an important role in the progression and treatment of alcohol addiction. While men show a higher prevalence of alcohol addiction, women are more susceptible to the adverse effects of excessive alcohol consumption. Additionally, women often rely on heavy drinking as a maladaptive coping mechanism to alleviate stress and anxiety, driven by negative affect. On the other hand, men are more likely to report heavy drinking and relapse in response to positive emotions and social influences. These sex-based differences underline the importance of understanding how vulnerability to alcohol addiction and its treatment varies in males and females.We used genetically heterogeneous rats to explore the behavioral traits that contribute to compulsivity, a key clinical feature of alcohol addiction. We found that motivation to self-administer alcohol was higher in males, while females showed higher compulsive alcohol self-administration. In males, motivation to self-administer alcohol showed a significant correlation with compulsivity, while in females compulsivity was predicted by higher basal corticosterone levels.These findings underlie the importance of sex-specific factors in compulsive alcohol self-administration, with potential prevention and treatment implications in alcohol addiction.

Allografts use in orthopedic surgery: trend change over the past 11 years from a regional tissue bank.

Allografts are the second most transplanted tissue in medicine after blood and are now increasingly used for both primary and revision surgery. Allografts have the advantages of lower donor site morbidity, availability of multiple grafts, and shorter operative time. The Banks represents the bridge between Donor and Recipient and guarantees the quality and safety of the distributed allografts Given the increasing interest in these tissues, a retrospective analysis of data collected from the Regional Musculoskeletal Tissue Bank registry over an 11-year period (2009-2019) was conducted. The statistical analyses used were the Shapiro-Wilk normality test and a Poisson regression model. From January 2009 to December 2019, a total of 14,199 musculoskeletal tissues stored in the Regional Musculoskeletal Tissue Bank were provided for surgical allograft procedures. In 2009, the number of allografts performed was 925; this figure has steadily increased to 1599 in 2019. Epiphyses were taken as the reference tissue with an almost constant trend over the period, while a significant increase was denoted for extensor mechanism allograft, ligaments, tendons and long bone corticals (p < 0.001), processed bone tissues had no change in trend (p = 0.841). There was also a gradual decrease in the rate of microbiological positivity, as determined by bacteriological and serological tests performed on the collected tissues. This phenomenon is due to improved sampling techniques and the training of a dedicated team. Thus, we have seen how the use of allografts in orthopedic surgery has increased over the past 11 years, uniformly in terms of tissue type, except for the noticeable increase in ligamentous tissue.

Chemical Information Processing by a Responsive Chemical System.

Nature has an extraordinary capacity to precisely regulate the chemical reactivity in a highly complex mixture of molecules that is present in the cell. External stimuli lead to transient up- and downregulation of chemical reactions and provide a means for a cell to process information arriving from the environment. The development of synthetic chemical systems with life-like properties requires strategies that allow likewise control over chemical reactivity in a complex environment. Here, we show a synthetic system that mimics the initial steps that take place when a natural signal transduction pathway is activated. Monophosphate nucleosides act as chemical triggers for the self-assembly of nanoreactors that upregulate chemical reactions between reagents present at low micromolar concentrations. Different nucleotides template different assemblies and hence activate different pathways, thus establishing a distinct connection between input and output molecules. Trigger-induced upregulation of chemical reactivity occurs for only a limited amount of time because the chemical triggers are gradually removed from the system by enzymes. It is shown that the same system transiently produces different output molecules depending on the chemical input that is provided.

Immune cell composition varies by age, sex and exposure to social adversity in free-ranging Rhesus Macaques.

Increasing age is associated with dysregulated immune function and increased inflammation-patterns that are also observed in individuals exposed to chronic social adversity. Yet we still know little about how social adversity impacts the immune system and how it might promote age-related diseases. Here, we investigated how immune cell diversity varied with age, sex and social adversity (operationalized as low social status) in free-ranging rhesus macaques. We found age-related signatures of immunosenescence, including lower proportions of CD20 + B cells, CD20 + /CD3 + ratio, and CD4 + /CD8 + T cell ratio - all signs of diminished antibody production. Age was associated with higher proportions of CD3 + /CD8 + Cytotoxic T cells, CD16 + /CD3- Natural Killer cells, CD3 + /CD4 + /CD25 + and CD3 + /CD8 + /CD25 + T cells, and CD14 + /CD16 + /HLA-DR + intermediate monocytes, and lower levels of CD14 + /CD16-/HLA-DR + classical monocytes, indicating greater amounts of inflammation and immune dysregulation. We also found a sex-dependent effect of exposure to social adversity (i.e., low social status). High-status males, relative to females, had higher CD20 + /CD3 + ratios and CD16 + /CD3 Natural Killer cell proportions, and lower proportions of CD8 + Cytotoxic T cells. Further, low-status females had higher proportions of cytotoxic T cells than high-status females, while the opposite was observed in males. High-status males had higher CD20 + /CD3 + ratios than low-status males. Together, our study identifies the strong age and sex-dependent effects of social adversity on immune cell proportions in a human-relevant primate model. Thus, these results provide novel insights into the combined effects of demography and social adversity on immunity and their potential contribution to age-related diseases in humans and other animals.

Transforaminal lumbar interbody fusion with a tantalum cage: lumbar lordosis redistribution and sacral slope restoration with a modified posterior technique.

BACKGROUND: Transforaminal lumbar interbody fusion (TLIF), a commonly used procedure in spine surgery, has the advantage of a lower incidence of nerve lesions compared to the posterior lumbar interbody fusion (PLIF) technique. The intersomatic arthrodesis has always been carried out with a single tantalum cage normally used for PLIF. Tantalum is a metal that is particularly used in orthopedic surgery. It has a modulus of elasticity similar to marrow and leads to high primary stability of the implant. MATERIALS AND METHODS: Our study was a retrospective monocentric observational study evaluating clinical and radiological outcomes of tantalum cages in a modified TLIF technique with posterior instrumentation and autologous and/or homologous posterolateral bone grafting. The aim of the study was to evaluate clinical outcomes and the increase in or redistribution of lumbar lordosis. The intersomatic arthrodesis was always carried out with a single tantalum cage normally used for PLIF to reduce the neurological risk. We retrospectively studied 105 patients who were treated with a modified unilateral TLIF approach by two surgeons between 2013 and 2018. We evaluated the Oswestry Disability Index (ODI), Visual Analogue Scale (VAS) for back pain, global lumbar lordosis, lordosis of L4-sacrum, segmental lordosis of functional motion units that underwent arthrodesis, pelvic tilt, pelvic incidence, and the sacral slope in 77 patients. All patients were suffering from grade III or IV Pfirrmann, instability, or foraminal post-laminectomy stenosis and/or grade I-II degenerative spondylolisthesis or low-grade isthmic spondylolisthesis. They had no significant sagittal imbalance, with a sagittal vertical axis (SVA) of < 5 mm. The average follow-up duration was 30 months. RESULTS: We achieved excellent clinical results, with only four cases of failure (5.2%). Moreover, we noticed a statistically significant redistribution of lumbar lordosis, with an average percentage increase in L4-S1 lordosis equal to 19.9% (P < 0.001), an average increase in the L4-S1/Lumbar lordosis (LL) ratio from 0.53 to 0.63 (P < 0.001), and a mean percentage increase in sacral slope equal to 7.6% (P < 0.001). CONCLUSION: Thanks to the properties of tantalum, our modified single-portal TLIF technique is a valid surgical solution to obtain a solid arthrodesis and restore the correct lumbar lordosis distribution while reducing neurological complications and the number of failures. LEVEL OF EVIDENCE: 4 Trial registration statement: retrospective observational study, no trial registration.

What Is the Role of Traction Test Radiographs in the Preoperative Planning of Adolescent Idiopathic Scoliosis?

Lower instrumented vertebra (LIV) selection is critical to avoid complications like adding-on. This study aims to determine the usefulness of the traction test (TR) in selecting the LIV during surgery for adolescent idiopathic scoliosis (AIS). We analyzed 42 AIS patients with Lenke 1 curves who had preoperative, postoperative, and at least 12-month follow-up X-rays, as well as preoperative side bending (SB) and TR radiograms. Neutral vertebra (NV), stable vertebra (SV), lower instrumented vertebra (LIV), and Cobb angles were identified and compared on all radiographic images. In 23 cases, the TR resulted in SV proximalization compared to the preoperative X-rays, while in 8 cases, SV-TR was more distal. This distalization occurred in 50% of Lenke 1C curves, where a greater correction of the distal curve was found. NV-TR was proximal to NV-preop in 9 cases, while NV-SB was proximal in 22 cases. LIV was proximal to SV-TR in 8 cases, while it was proximal to SV-preop in 22. One patient with LIV proximal to SV-TR developed adding-on. In conclusion, the TR is crucial in AIS preoperative planning as it provides information distinct from that of standard X-rays and SB: (1) it better assesses gravitational stability than rotational stability; and (2) choosing LIV equal to or proximal to SV-TR may prevent adding-on, except in 'flexible' Lenke 1C curves where LIV should be equal or distal to SV-preop.

Sequence-selective duplex formation and template effect in recognition-encoded oligoanilines.

A new family of duplex-forming recognition encoded oligomers, capable of sequence selective duplex formation and template directed synthesis, was developed. Monomers equipped with both amine and aldehyde groups were functionalized with 2-trifluoromethylphenol or phosphine oxide as H-bond recognition units. Duplex formation and assembly properties of homo- and hetero-oligomers were studied by 19F and 1H NMR experiments in chloroform. The designed backbone prevents the undesired 1,2-folding allowing sequence-selective duplex formation, and the stability of the antiparallel duplex is 3-fold higher than the parallel arrangement. Dynamic combinatorial chemistry was exploited for the templated synthesis of complementary oligomers, showing that an aniline dimer can template the formation of the complementary imine. The key role of the H-bond recognition confers to the system the ability to discriminate a mutated donor monomer incapable of H-bonding. Sequence selective duplex formation combined with the template effect makes this system an attractive target for further studies.

Patient and caregiver experiences with pantothenate kinase-associated neurodegeneration (PKAN): results from a patient community survey.

BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive genetic disorder of PANK2, which enables mitochondrial synthesis of coenzyme A. Its loss causes neurodegeneration with iron accumulation primarily in motor-related brain areas. Symptoms include dystonia, parkinsonism, and other disabilities. PKAN has been categorized as classic PKAN, with an age of onset ≤ 10 years, rapid progression, and early disability or death; and atypical PKAN, with later onset, slower progression, generally milder, and more diverse symptom manifestations. Available treatments are mostly palliative. Information on the lived experience of patients with PKAN and their caregivers or on community-level disease burden is limited. It is necessary to engage patients as partners to expand our understanding and improve clinical outcomes. This patient-oriented research study used multiple-choice and free-form question surveys distributed by patient organizations to collect information on the manifestations and disease burden of PKAN. It also assessed respondents' experiences and preferences with clinical research to inform future clinical trials. RESULTS: The analysis included 166 surveys. Most respondents (87%) were parents of a patient with PKAN and 7% were patients, with 80% from Europe and North America. The study cohort included 85 patients with classic PKAN (mean ± SD age of onset 4.4 ± 2.79 years), 65 with atypical PKAN (13.8 ± 4.79 years), and 16 identified as "not sure". Respondents reported gait disturbances and dystonia most often in both groups, with 44% unable to walk. The classic PKAN group reported more speech, swallowing, and visual difficulties and more severe motor problems than the atypical PKAN group. Dystonia and speech/swallowing difficulties were reported as the most challenging symptoms. Most respondents reported using multiple medications, primarily anticonvulsants and antiparkinsonian drugs, and about half had participated in a clinical research study. Study participants reported the most difficulties with the physical exertion associated with imaging assessments and travel to assessment sites. CONCLUSIONS: The survey results support the dichotomy between classic and atypical PKAN that extends beyond the age of onset. Inclusion of patients as clinical research partners shows promise as a pathway to improving clinical trials and providing more efficacious PKAN therapies.

An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver.

A perimetastatic capsule is a strong positive prognostic factor in liver metastases, but its origin remains unclear. Here, we systematically quantify the capsule's extent and cellular composition in 263 patients with colorectal cancer liver metastases to investigate its clinical significance and origin. We show that survival improves proportionally with increasing encapsulation and decreasing tumor-hepatocyte contact. Immunostaining reveals the gradual zonation of the capsule, transitioning from benign-like NGFRhigh stroma at the liver edge to FAPhigh stroma towards the tumor. Encapsulation correlates with decreased tumor viability and preoperative chemotherapy. In mice, chemotherapy and tumor cell ablation induce capsule formation. Our results suggest that encapsulation develops where tumor invasion into the liver plates stalls, representing a reparative process rather than tumor-induced desmoplasia. We propose a model of metastases growth, where the efficient tumor colonization of the liver parenchyma and a reparative liver injury reaction are opposing determinants of metastasis aggressiveness.

Paraparesis and congenital severe hyperkyphosis in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: A rare deformity management during the Sars-Cov-2 pandemic.

Introduction: Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) syndrome can be classified into two types: type I (isolated) without extragenital abnormalities; type II (associated) with the presence of extragenital dimorphisms. Skeletal abnormalities are the second most frequent extragenital manifestations. Research question: Association between MRKH and congenital scoliosis has been described; on the contrary, hyperkyphosis is very rare and sparsely described in the medical literature. Here we report our experience in the management of thoracolumbar hyperkyphosis in 16-year-old patient diagnosed with MRKH syndrome with an acute neurological impairment due to T11-T12 disc herniation. Material and methods: Clinical and radiological images of the case were retrieved from the medical notes, operative records and imaging system. Results: Posterior surgical correction was proposed to treat the severe spinal deformity; however, surgery was delayed because of SARS-CoV2 pandemic outbreak. During the pandemic, the patient had a major clinical and radiological deterioration with development of paraparesis. Complete clinical resolution of the paraparesis and restoration of balance was achieved with a two stage surgical approach, with a first anterior stage followed by a delayed posterior approach aimed at deformity correction. Discussion: Congenital kyphosis are rare deformities that can progress rapidly leading to severe neurological deficits and worsening of the deformity. When patient has neurological deficit the surgical strategy to address the neurological problem first and plan the more complex and demanding corrective surgery remains a valid strategy that must be consider. Conclusion: This is the first reported case of hyperkyphosis in Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) syndrome surgically treated.

Differentiated Effect of Smoking on Disease Activity and Quality of Life among Different Spondyloarthritis Phenotypes.

BACKGROUND AND AIMS: The effect of smoking on disease activity and quality of life (QoL) in spondyloarthritis (SpA) is far from clear. We aimed to evaluate the relationship between smoking and these outcomes in patients with axial SpA (axSpA) and psoriatic arthritis (PsA). PATIENTS AND METHODS: This cross-sectional observational multicenter study included 242 patients with axSpA and 90 with PsA. The association between conventional cardiovascular risk factors and disease activity as well as QoL, in both SpA phenotypes was evaluated. For this, univariate and multivariate regression analyses were performed, as well as confirmatory meta-analyses. RESULTS: Regardless of age, sex, or disease duration, patients with axSpA showed significantly less association with obesity (OR 0.50 (0.26-0.96), p = 0.03) and hypertension (OR 0.33 (0.18-0.62), p = 0.0005). However, axSpA was significantly associated with smoking (OR 2.62 (1.36-5.04), p = 0.004). Patients with axSpA were more likely to be in a category of high disease activity compared with PsA (OR 2.86, p = 0.0006). Regardless of sex, age, disease duration, and education level, smoking was significantly associated with higher disease activity in axSpA (OR 1.88, p = 0.027). A fixed-effects model meta-analysis (OR 1.70, p = 0.038) confirmed the association between tobacco and disease activity. No relationship was found between smoking (or other cardiometabolic risk factors) and structural damage or worse QoL in either disease. CONCLUSIONS: Although the cardiometabolic risk profile is clearly different between both SpA phenotypes, the only clear link between these factors and increased disease activity was observed between smoking and axSpA. Our findings need further confirmation.

The oxyhaemoglobin dissociation curve is generally left-shifted in COVID-19 patients at admission to hospital, and this is associated with lower mortality.

Lung damage caused by SARS-Cov-2 virus results in marked arterial hypoxia, accompanied in many cases by hypocapnia. The literature is inconclusive as to whether these conditions induce alteration of the affinity of haemoglobin for oxygen. We studied the oxyhaemoglobin dissociation curves (ODCs) of 517 patients hospitalized with coronavirus disease 2019 (COVID-19) for whom arterial blood gas analysis (BGA) was performed upon hospitalization (i.e., before treatment). With respect to a conventional normal p50 (pO2 at 50% saturation of haemoglobin) of 27 mmHg, 76% had a lower standardized p50 (p50s) and 85% a lower in vivo p50 (p50i). In a 33-patient subgroup with follow-up BGAs after 3, 6, 9, 12, 15 and 18 days' treatment, p50s and p50i exhibited statistically significant differences between baseline values and values recorded at all these time points. The 30-day Kaplan-Meier survival curves of COVID-19 patients stratified by p50i level show a higher probability of survival among patients who at admission had p50 values below 27 mmHg (p = 0.012). Whether the observed alteration of the affinity of haemoglobin for oxygen in COVID-19 patients is a direct or indirect effect of the virus on haemoglobin is unknown.

At-admission HbA1c levels in hospitalized COVID-19 participants with and without known diabetes.

BACKGROUND: To examine glycaemic status, and the impact of at-admission HbA1c levels on outcome, in a large group of participants hospitalized for COVID-19. METHODS: We inclued 515 participants with confirmed COVID-19 infection, with or without known diabetes, who met the following additional criteria: 1) age > 18 years, 2) HbA1c was determined at admission; 3) fasting plasma glucose was determined in the week of admission, and 4) discharge or death was reached before the end of the study. We examined attributes of participants at admission and 3-6 months post-discharge. To assess the associations of pre-admission attributes with in-hospital mortality, logistic regression analyses were performed. RESULTS: Mean age was 70 years, 98.8% were of white race, 49% were female, 31% had known diabetes (KD), an additional 7% met the HbA1c criterion for diabetes, and 13.6% died. In participants with KD, FPG and HbA1c levels were not associated with mortality in adjusted analyses; however, in participants without KD, whereas FPG showed direct association with mortality, HbA1c showed slight inverse association. CONCLUSIONS: There was a very high prevalence of people without KD with HbA1c levels above normal at-admission. This alteration does not seem to have been related to blood glucose levels.

Engaging the Guatemala Scientific Diaspora: The Power of Networking and Shared Learning.

The underdevelopment of the higher education system in Guatemala and the fragility of its science and technology (S&T) contexts have compelled a significant number of talented Guatemalan scientists to be trained, educated, and employed abroad. The relocation of such skilled human power to different countries and regions has resulted in a growing Guatemalan Scientific Diaspora (GSD). Until recently, the emigration of scientists from the Global South to scientifically advanced countries in the North was studied as it negatively impacted the countries of origin. However, technological upgrades and globalization have progressively shifted the paradigm in which such scientific diasporas interact and connect, thus enabling them to influence their home countries positively. Due to the lack of knowledge-based evidence and functioning connecting platforms, the value and potential of the GSD in their involvement in proposing solutions to complex socio-economic, environmental, and other challenges faced by Guatemalan society remain unknown. Moreover, the lack of interaction of relevant stakeholders (S&T policy agents, international partners, higher education institutions and research centers, industry, and relevant not governmental organizations) represents a pervasive obstacle to the untapped impact of the GSD in the country. This study outlines the Guatemalan scientific diasporas' networking as a mechanism for building research excellence and intellectual capital. This force could respond to the need to strengthen the national science capacities and meet the demands for knowledge production and access to broader sectors of society. This research applied qualitative methodology that, through the conduction of focus group discussions and semi-structured interviews with members of the Guatemalan scientific community and relevant key stakeholders, delved into the existence and articulation of the GSD and potential stages for their engagement with their country of origin. Findings highlight the importance of digital and technological pathways that might leverage the GSD's knowledge and experience, channeling skills, and international connections for better interaction with the Guatemalan society. Furthermore, the discussion addresses how technology might turn brain drain into brain circulation, enabling the articulation of the GSD as a viable opportunity to generate collaboration between scientists abroad and local actors, ultimately impacting the building and development of Guatemalan science and national research capacities.

Does Risser Casting for Adolescent Idiopathic Scoliosis Still Have a Role in the Treatment of Curves Larger Than 40°? A Case Control Study with Bracing.

Background: The most common conservative treatment for Adolescent Idiopathic Scoliosis (AIS) is bracing. However, several papers questioned the effectiveness of bracing for curves between 40° and 50° Cobb: the effectiveness in preventing curve progression could be as low as 35%. Seriate casting is considered a standard approach in early onset scoliosis; however, in the setting of AIS, cast treatment is seldom utilized, with only few studies reporting on its effectiveness. Aim of the study: The main aim of the study is to determine whether a seriate casting with Risser casts associated with bracing is more effective in preventing curve progression than bracing alone in curves larger than 40°. Furthermore, the secondary endpoints were: (1) is there a difference in effectiveness of casting between Thoracic (T) and Thoracolumbar/Lumbar (TL/L) curves? (2) Does the 'in cast' correction predicts the treatment outcome? (3) What is the effect on thoracic kyphosis of casting? Methods: This is a retrospective monocentric case−control study; through an Institutional Database search we identified all the patients treated at our institution between 1 January 2017 and 31 December 2020, with a diagnosis of AIS, Risser grade between 0 and 4 at the beginning of the treatment, at least one curve above 40° Cobb and treatment with either seriate Risser casting and bracing (Study Group, SG) or bracing alone (Control Group, CG). Standing full spine X-rays in AP and LL are obtained before and after the cast treatment; only AP standing full spine X-rays 'in-cast' are obtained for each cast made. Patients were stratified according to the curve behavior at the end of treatment (Risser 5): progression was defined as ≥6° increase in the curve magnitude or fusion needed; stabilization is defined as a change in curve by ±5°; and improvement was defined as ≥6° reduction in the curve. Results: For the final analysis, 55 compliant patients (12 M, 43 F, mean age 13.5 ± 1.6) were included in the SG and 27 (4 M, 23 F, mean age 13.6 ± 1.6) in the CG. Eight (14.5%) patients in the SG failed the conservative treatment while 14 (51.3%) failed in the CG. Consequently, the Relative Risk for progression in the Efficacy Analysis was 1.8 (95% CI 1, 3−2.6, p = 0.001), and the Number Needed to Treat was 2,4. No significant difference was found between the T and TL/L curves concerning the 'progressive' endpoint (z-score 0.263, p = 0.79). The mean percentage of 'in cast' curve reduction was 40.1 ± 15.2%; no significant correlation was found between the percentage of correction and the outcome (Spearman Correlation Coefficient 0.18). Finally, no significant differences between baseline and end of FU TK were found (32° ± 16.2 vs. 29.6 ± 15.8, p = ns). Discussion: Seriate Risser casting for AIS with larger curves (>40° Cobb) is effective in reducing curve progression when compared with full time bracing alone in treatment compliant patients. The treatment is equally effective in controlling T and TL/L curves; furthermore, a slight but non-significant decrease in TK was observed in patients treated with casting. This type of treatment should be considered for AIS patients who present with large curves to potentially reduce the percentage of surgical cases. Short Abstract: The aim of the study is to determine whether seriate Risser casting associated with bracing is more effective in preventing curve progression than bracing alone in curves larger than 40°. This is a retrospective monocentric case−control study; we identified all the patients treated at our institution with a diagnosis of AIS, Risser grade 0−4 at the beginning of the treatment, at least one curve above 40° Cobb (35° if treated with bracing alone) and treatment with either seriate Risser casting and bracing (Study Group, SG) or bracing alone (Control Group, CG). Fifty-five patients (12 M, 43 F, mean age 13.5 ± 1.6) were included in the SG and 30 (5 M, 25 F, mean age 13.9 ± 1.7) in the CG. Eight (14,5%) patients in the SG failed the conservative treatment while fifteen (50%) failed in the CG. Consequently, the Relative Risk for progression in the Efficacy Analysis was 1.8 (95% CI 1.3−2.6, p = 0.001), and the Number Needed to Treat was 2,4. Seriate Risser casting for AIS with larger curves (>40°) is effective in reducing curve progression when compared with full time bracing alone. This type of treatment should be considered for AIS patients who present with large curves.

Construct Validity of the Routine Assessment of Patient Index Data 3 (RAPID3) in the Evaluation of Axial Spondyloarthritis.

OBJECTIVE: Although there are different tools to evaluate axial spondyloarthritis (axSpA), they are hardly used in routine clinical practice due to time constraints. The Routine Assessment of Patient Index Data 3 (RAPID3) is a composite measure feasible for use as a sole metric in busy clinics. We aimed to test its measurement properties in patients with axial SpA in a real-world clinical setting. METHODS: This cross-sectional study included 131 consecutive patients with axial SpA. The convergent (Spearman ρ) and discriminant (receiver-operating characteristic [ROC] curve analysis) validity of RAPID3 were tested against several axSpA-specific measures (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score [ASDAS], Bath Ankylosing Spondylitis Functional Index [BASFI], and modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]). A multivariate model was built to detect disease factors associated with RAPID3 remission (values ≤ 3). RESULTS: The study included 82 men and 49 women, with a median age of 55 (IQR 46-61) years, and a median disease duration of 11 (IQR 6-24) years. Mean RAPID3 was 9.45 ± 6.7. The BASDAI showed moderate correlation with ASDAS (ρ 0.66, P < 0.0001), but higher correlations with BASFI (ρ 0.78, P < 0.0001) and RAPID3 (ρ 0.75, P < 0.0001). The ASDAS had moderate correlations with BASFI, BASDAI, and RAPID3 (ranges 0.66-0.68, P < 0.0001). Higher correlations were found between BASFI and BASDAI (ρ 0.78, P < 0.0001), and BASFI and RAPID3 (ρ 0.73, P < 0.0001). The mSASSS did not show any correlation with any of the above composite measures. κ agreement between RAPID3 remission and other SpA remission criteria was moderate (κ 0.46-0.56). The RAPID3 thresholds to define remission ranged from values ≤ 2 to ≤ 6 with areas under the ROC curve between 0.86-0.91. Female sex (OR 0.34, 95% CI 0.12-0.90, P = 0.03) and nonsteroidal antiinflammatory drug intake (OR 0.26, 95% CI 0.10-0.66, P = 0.005) were independently associated with lower odds of achieving RAPID3 remission. CONCLUSION: RAPID3 demonstrated construct validity in this cross-sectional study. This index can be useful for a more comprehensive assessment of axSpA in busy clinical settings.