Impacts of conservative treatment on the clinical manifestations of obstructive sleep apnea-systematic review and meta-analysis.

INTRODUCTION: Obstructive sleep apnea (OSA) is a chronic disease with a high populational prevalence that is characterized as airway closure during sleep. Treatment is multidisciplinary and varies according to each case. Continuous positive airway pressure (CPAP), oral appliances, and surgery are the primary therapeutic options. Non-invasive conservative treatments such as sleep hygiene, positional therapy, physical exercises, and weight loss aim to reduce the worsening of the disease while being complementary to the invasive primary treatment. OBJECTIVE: To analyze the impact of non-invasive conservative therapies on the clinical manifestations of OSA syndrome (OSA), compared with other interventions. METHOD: This was a systematic review with meta-analysis. The searches were performed without filters for the time period, type of publication, or language. Randomized clinical trials on subjects over 18 years of age diagnosed with untreated OSA were included. Responses to non-invasive conservative treatment were compared with responses to the primary intervention. Primary outcomes were assessed using the Epworth Sleepiness Scale and/or Functional Outcomes of Sleep Questionnaire (FOSQ). RESULTS: A total of eight studies were included in the review. The heterogeneity of the effect was estimated at 89.77%. Six studies compared conservative treatment with CPAP, one with oral appliances, and one with oropharyngeal exercises. Using the Epworth Sleepiness Scale measurements, the standardized difference in the estimated means, based on the random-effects model, was 0.457 (95% CI (1.082 to 0.169)) and the mean result did not differ significantly from zero (z = 1.43; p = 0.153). The conservative therapies assessed in this study improved the subjective quality of sleep, although the post-treatment ESE scores did not show significant results. The reduction in AHI and better outcomes in the evaluated domains, as well as in cognition and mood, were superior in the groups that received CPAP and IOD. CONCLUSION: The most commonly used treatments of choice for OSA are invasive, including the use of CPAP, oral appliances, and surgeries, being the most utilized options. This study demonstrated that non-invasive conservative treatments, such as sleep hygiene, yield results as effective as invasive treatments. Further studies are needed to confirm this result and to predict whether invasive treatment can be used as the primary treatment or only as a supplement.

Hydrodynamic cavitation-assisted acid pretreatment and fed-batch simultaneous saccharification and co-fermentation for ethanol production from sugarcane bagasse using immobilized cells of Scheffersomyces parashehatae.

A new alternative for hydrodynamic cavitation-assisted pretreatment of sugarcane bagasse was proposed, along with a simultaneous saccharification and co-fermentation (SSCF) process performed in interconnected columns. Influential variables in the pretreatment were evaluated using a statistical design, indicating that an ozone flow rate of 10 mg min-1 and a pH of 5.10 resulted in 86 % and 72 % glucan and xylan hydrolysis yields, respectively, in the subsequent enzymatic hydrolysis process. Under these optimized conditions, iron sulfate (15 mg L-1) was added to assess Fenton pretreatment, resulting in glucan and xylan hydrolysis yields of 92 % and 71 %, respectively, in a material pretreated for 10 min. In SSCF, ethanol volumetric productivities of 0.33 g L-1 h-1 and of 0.54 g L-1 h-1 were obtained in batch and fed-batch operation modes, achieving 26 g L-1 of ethanol in 48 h in the latter mode.

Synchronous Observation of Bell Nonlocality and State-Dependent Contextuality.

Bell nonlocality and Kochen-Specker contextuality are two remarkable nonclassical features of quantum theory, related to strong correlations between outcomes of measurements performed on quantum systems. Both phenomena can be witnessed by the violation of certain inequalities, the simplest and most important of which are the Clauser-Horne-Shimony-Holt (CHSH) and the Klyachko-Can-Binicioglu-Shumovski (KCBS), for Bell nonlocality and Kochen-Specker contextuality, respectively. It has been shown that, using the most common interpretation of Bell scenarios, quantum systems cannot violate both inequalities concomitantly, thus suggesting a monogamous relation between the two phenomena. In this Letter, we show that the joint consideration of the CHSH and KCBS inequalities naturally calls for the so-called generalized Bell scenarios, which, contrary to the previous results, allows for joint violation of them. In fact, this result is not a special feature of such inequalities: We provide very strong evidence that there is no monogamy between nonlocality and contextuality in any scenario where both phenomena can be observed. We also implement a photonic experiment to test the synchronous violation of both CHSH and KCBS inequalities. Our results agree with the theoretical predictions, thereby providing experimental proof of the coexistence of Bell nonlocality and contextuality in the simplest scenario, and lead to novel possibilities where both concepts could be jointly employed for quantum information processing protocols.

Long-term outcome of redo discectomy for recurrent lumbar disc herniations.

PURPOSE: Recurrent lumbar disc herniation (RLDH) is an important cause of morbidity and healthcare costs. The goal of this investigation is to assess surgical outcomes and their predictors in patients who underwent revision discectomy for RLDH, with a minimum follow-up of ten years, to shed light on the best treatment to offer to these patients. METHODS: Patients who underwent revision discectomy to treat RLDH between 2004 and 2011 in our Department were enrolled. Demographic, clinical, and surgical data were collected. The need of third intervention for RLDH was the primary outcome. Patient's satisfaction, Core Outcome Measures Index, Oswestry Disability Index, and EuroQoL-5D scores were also evaluated. RESULTS: This study includes 55 patients, with a mean follow-up time of 144 months [112-199]. In this period, a third intervention was needed in 30.9% (n = 17) of patients. Most recurrences took place in the first 2 years after the second surgery (58.8%, n = 10) and the risk of needing a third surgery decreased over time. After 5 years, the probability of not having surgery for recurrence was 71% [CI 95%: 60-84%], with a tendency to stabilize after that. An interval between the first discectomy and the surgery for recurrence shorter than 7.6 months was identified as a predictor for a second recurrence. CONCLUSION: The risk of needing a third surgery seems to stabilize after five years. Patients with an early recurrence after the first discectomy seem to have a higher risk of a new recurrence, so an arthrodesis might be worth considering.

Neuroprotection is improved by watertightness of fetal spina bifida repair in the sheep model.

OBJECTIVES: A contributing factor to unsuccessful prenatal spina bifida aperta (SBA) repair via an open approach may be incomplete neurosurgical repair causing persistent in-utero leakage of cerebrospinal fluid (CSF) and exposure of the fetal spinal cord to amniotic fluid. We aimed to investigate the neurostructural and neurofunctional efficacy of watertight prenatal SBA repair in a validated SBA fetal lamb model. METHODS: A well-powered superiority study was conducted in the validated SBA fetal lamb model (n = 7 per group). The outcomes of lambs which underwent watertight or non-watertight multilayer repair through an open approach were compared to those of unrepaired SBA lambs (historical controls) at delivery (term = 145 days). At ∼75 days, fetal lambs underwent standardized induction of lumbar SBA. At ∼100 days, they were assigned to an either watertight or non-watertight layered repair group based on an intraoperative watertightness test using subcutaneous fluorescein injection. At 1-2 days postnatally, as primary outcome, we assessed reversal of hindbrain herniation using magnetic resonance imaging (MRI). Secondary proxies of neuroprotection were: absence of CSF leakage at the repair site; hindlimb motor function based on joint-movement score, locomotor grade and Motor Evoked Potential (MEP); four-score neuroprotection scale, encompassing live birth, complete hindbrain herniation reversal, absence of CSF leakage and joint-movement score ≥ 9/15; and brain and spinal cord histology and immunohistochemistry. As the watertightness test cannot be used clinically due to its invasiveness, we developed a potential surrogate intraoperative three-score skin-repair-quality scale based on visual assessment of the quality of the skin repair (suture inter-run distance ≤ 3 mm, absence of tear and absence of ischemia), with high quality defined by a score ≥ 2/3 and low quality by a score < 2/3, and assessed its relationship with improved outcome. RESULTS: Compared with unrepaired lambs, lambs with watertight repair achieved a high level of neuroprotection (neuroprotection score of 4/4 in 5/7 vs 0/7 lambs) as evidenced by: a significant 100% (vs 14%) reversal of hindbrain herniation on MRI; low CSF leakage (14% vs 100%); better hindlimb motor function, with higher joint-movement score, locomotor grade and MEP area under the curve and peak-to-peak amplitude; higher neuronal density in the hippocampus and corpus callosum; and higher reactive astrogliosis at the SBA lesion epicenter. Conversely, lambs with non-watertight SBA repair did not achieve the same level of neuroprotection (score of 4/4 in 1/7 lambs) compared with unrepaired lambs, with: a non-significant 86% (vs 14%) reversal of hindbrain herniation; high CSF leakage (43% vs 100%); no improvement in motor function; low brain neuron count in both the hippocampus and corpus callosum; and small spinal astroglial cell area at the epicenter. Both watertight layered repair and high (≥ 2/3) intraoperative skin-repair-quality score were associated with improved outcome, but the watertightness test and skin-repair-quality scale could not be used interchangeably due to result discrepancies. CONCLUSIONS: Watertight layered fetal SBA repair is neuroprotective since it improves brain and spinal-cord structure and function in the fetal lamb model. This translational research has important clinical implications. A neurosurgical technique that achieves watertightness should be adopted in all fetal centers to improve neuroprotection. Future clinical studies could assess whether a high skin-repair-quality score (≥ 2/3) correlates with neuroprotection. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Systematic review of the registered clinical trials for oncological hyperthermia treatment.

BACKGROUND: The use of heat to treat various diseases is called hyperthermia treatment (HT). Since the 1970s, the anti-cancer effects of HT have been investigated. Different HT techniques can be categorized as local, regional and whole-body hyperthermia treatment (WBHT). We aim to provide a summary of recent research done on HT to treat cancer. METHODS: In July 2020 ClinicalTrials.gov were systematically searched for all trials including hyperthermia and cancer registered between 2000 and 2020. Studies were excluded when they did not concern hyperthermal treatment, when they were not oncological studies, when they were observational or other non-interventional studies. RESULTS: Of 1654 identified trials, 235 were included. Of these 235 studies, 123 described the use of HIPEC (52.3%), 44 other types of regional HT (18.7%), 45 local HT (19.1%) and 15 WBHT (6.4%). A steady increase (720%) in research to hyperthermic intraperitoneal chemotherapy (HIPEC) can be observed in the last decade. Although HIPEC is the most researched HT modality, an evolution in other HT technologies could be observed during the past decade. CONCLUSIONS: Research to HT to treat cancer has expanded fast. Some techniques, for example HIPEC start to be used outside of research context, but overall, more research is needed to establish a clear effect of these HT techniques.

Malnutrition and nutritional deficiencies in children with cerebral palsy: a systematic review and meta-analysis.

OBJECTIVES: This systematic review study and meta-analysis sought to estimate the prevalence of malnutrition and nutritional deficiencies in children with cerebral palsy (CP). STUDY DESIGN: This is a systematic review and meta-analysis. METHODS: The systematic review was conducted according to the PRISMA guidelines. The articles were chosen using the PubMed, Embase, Scopus, Web of Science, Cochrane Library, SciELO, and Lilacs databases and the bibliographical reference lists of the articles. No limitations were placed on the time of publication, but the articles had to include children from 0 to 18 years old with CP who presented the prevalence of malnutrition and nutritional deficiencies. The methodological quality of the articles was assessed using the verification list for analytical cross-sectional studies, the Newcastle-Ottawa scale, and the Cochrane Collaboration tool for randomized studies. The meta-analysis of proportions was conducted based on the prevalence data for malnutrition or nutritional deficiencies. The study is registered in PROSPERO under CRD number 42020175068. RESULTS: Sixty-seven articles (N = 453,804) published between 1986 and 2019 were included. Most of the articles presented a low risk of bias and no publication was excluded for quality reasons. The most widely used anthropometric index for diagnosing nutritional status was weight-to-age and the estimated prevalence of malnutrition was 40% (95% CI = 28.0-53.0). Nutrient deficiency was investigated by nine publications, with hypocalcemia and reduced serum concentrations of zinc, copper, and vitamin D being reported the most. CONCLUSIONS: We found a high rate of malnutrition in the population in this review, moreover, we suggest that some nutritional deficiencies are associated with food deficit and that the socio-economic and age factors of these children may relate with the poor nutritional outcome. This makes monitoring and personalized nutritional management necessary, in accordance with the characteristics and particularities of children with CP.

Use of fermentation processes for improving the dissolution of phosphorus and its recovery from waste activated sludge.

Recycling phosphorus from waste activated sludge has attracted a lot of interest to tackle the problem of phosphorus stocks depletion and the increase in food demand. In this study, the use of fermentation processes was investigated to enhance phosphorus dissolution from waste activated sludge to improve its recycling. Two fermentation processes, bioacidification and dark fermentation, were used on two different sludges fermented with wheat starch syrup in continuous operating conditions. Hydrogen yield from the co-substrate fermentation with waste activated sludge reached 3.9 mmolH2.gCODcosubstrate-1 yield during dark fermentation process and was negligible during bioacidification. Dissolved phosphorus in the waste activated sludge increased by 68% during bioacidification and by 43% during dark fermentation. In both processes, phosphorus dissolution was accompanied by iron, calcium and magnesium dissolution. Results show that fermentation enhances phosphorus dissolution in waste activated sludge to improve its recovery along with hydrogen and organic acids.

Tolerability of long-term temperature controlled whole-body thermal treatment in advanced cancer-bearing dogs.

Aim: In oncology, thermal therapy is the application of external heat to fight cancer cells. The goal of whole-body thermal treatment (WBTT) is to raise the patient's core temperature to 39-42 °C, and represents the only thermal treatment modality that can act on both the primary tumor and distant metastases. However, WBTT carries potential risks for toxicity when applied without accurate thermometry and monitoring.Methods: ElmediX has developed a medical device, HyperTherm, to deliver long-term controlled and accurate WBTT (41.5 °C, up to 8 h). The safety of the device and thermal treatment protocol was initially evaluated in minipigs, and we present the confirmation of tolerability of WBTT in dogs with advanced cancer, in combination with a reduced dose of radiotherapy or chemotherapy.Results: Thermometry in liver, rectum, and tumor confirmed a homogeneous heating of these body parts. Monitoring of clinical parameters showed acceptable and reversible changes in liver, cardiac, muscle and coagulation parameters, as was expected. Combination of WBTT with both radiotherapy and chemotherapy only caused some low-grade adverse events.Conclusion: We conclude that our findings support the safe use of HyperTherm-mediated WBTT for canine patients with advanced malignancies. They also tend to support a genuine therapeutic potential for long-term WBTT which needs to be confirmed on a larger dog patient population. Combined with previously reported safety results in minipigs, these contribute to support the ongoing clinical evaluation of WBTT in advanced human cancer patients.

Multi-Matrix Approach for the Analysis of Bicalutamide Residues in Oncology Centers by HPLC-FLD.

Cytostatics are toxic pharmaceuticals, whose presence in surfaces puts healthcare workers at risk. These drugs might also end up in hospital effluents (HWW), potentially damaging aquatic ecosystems. Bicalutamide is a cytostatic extensively consumed worldwide, but few analytical methods exist for its quantification and most of them require advanced techniques, such as liquid chromatography mass spectrometry (LC-MS), which are very complex and expensive for large monitoring studies. Therefore, a simple but reliable multi-matrix high performance liquid chromatographic method, with fluorescence detection, was developed and validated to rapidly screen abnormal concentrations of bicalutamide in HWW and relevant contamination levels of bicalutamide in indoor surfaces (>100 pg/cm2), prior to confirmation by LC-MS. The method presents good linearity and relatively low method detection limits (HWW: 0.14 ng/mL; surfaces: 0.28 pg/cm2). Global uncertainty was below 20% for concentrations higher than 25 ng/mL (HWW) and 50 pg/cm2 (surfaces); global uncertainty was little affected by the matrix. Therefore, a multi-matrix assessment could be achieved with this method, thus contributing to a holistic quantification of bicalutamide along the cytostatic circuit. Bicalutamide was not detected in any of the grab samples from a Portuguese hospital, but an enlarged sampling is required to conclude about its occurrence and exposure risks.

Instruments to evaluate undergraduate healthcare student learning styles globally: A scoping review.

BACKGROUND: Recognizing learning styles is important to maximizing learning outcomes and many instruments are available to investigate learning styles. OBJECTIVE: To investigate instruments with evidence of validity and reliability most commonly used to evaluate undergraduate healthcare student learning styles globally. METHOD: This scoping review of literature was guided by The Joanna Briggs Institute's recommendations for conducting scoping reviews and the PRISMA-ScR (extension for scoping reviews). The protocol is available for access. DATA SOURCES: Databases searched included Cumulative Index to Nursing and Allied Health Literature, PubMed, Web of Science, and Scopus. Inclusion criteria were: fully accessible; written in English, Portuguese, or Spanish; and used reliable and/or validated instruments to describe healthcare student learning styles. Articles were excluded if the sample included healthcare professionals, there was no report of the instrument validity and reliability, or was not fully accessible. Data were extracted from each article and entered into Microsoft Office Excel documents for analysis. RESULTS: Forty-seven articles were selected for full review, including cross-sectional, interventional, and longitudinal studies. Eleven instruments were identified with evidence of reliability and validity for assessing undergraduate healthcare student learning styles globally. The most frequently used instruments were Visual, Aural, Read-Write, and Kinesthetic; Kolb's Learning Styles Inventory; and the Honey-Alonso Questionnaire. Most instruments were developed based on a theoretical framework and/or model. CONCLUSION: This scoping review adds to the literature an overview of available instruments which measure healthcare student learning styles with evidence of both reliability and validity. The results indicate the need for further studies to improve learning style instruments for use in intervention studies aimed at improving the teaching-learning process for healthcare students.

Structural and histochemical attributes of secretory ducts and cavities in leaves of four species of Calophyllaceae J. Agardh in Amazonian savannas.

This study represents an important contribution to the structural, histochemical and biological understanding of ducts and cavities in leaves of four species of Calophyllaceae that occur in Amazonian savannas. Samples of adult leaves were processed using light, scanning and transmission electron microscopy, as per usual methods for plant anatomy. In paradermal sections, the lumina of ducts are elongated while those of cavities are short. Ducts occur exclusively in the central rib and are abundant in Kielmeyera rubriflora Cambess and Kielmeyera coriacea Mart. and Zucc and larger than in Calophyllum brasiliense Cambess and Caraipa densifolia Mart. In mesophyll, the type of secretory structure and distribution pattern of the ducts and cavities are distinct. In most species, the secreted metabolites are similar and consist of phenolic compounds, lipids, essential oils with oleoresins, mucilage, neutral polysaccharides, proteins and alkaloids, except in K. coriacea, which does not contain oleoresin. The secretion is probably synthesized by mitochondria, rough endoplasmic reticulum, ribosomes and dictyosomes and is externalized toward the lumen by granulocrine and eccrine processes. In addition to being of diagnostic value for species identification, the attributes of the lumen shape, type of secretory structure, distribution pattern, identified metabolites and secretion mechanism are important for understanding the biological roles of ducts and cavities. The identified metabolites reveal a capacity for adaptation, resistance and protection from the action of herbivores and pathogens, and in water retention.

Cytostatics in Indoor Environment: An Update of Analytical Methods.

Periodic and adequate environmental monitoring programs are crucial to assess and reduce the occupational exposure of healthcare workers to cytostatics. The analytical methods employed should be rapid, reliable, sensitive, standardized, and include multiple compounds. A critical overview of recent overall procedures for surface and air contamination with cytostatics in workplace settings is presented, with a focus on sampling, sample preparation, and instrumental considerations. Limitations are also addressed and some recommendations and advice are provided. Since dermal absorption is the main exposure route, surface contamination is the preferred indicator of biological uptake and its methods have significantly improved. In contrast, cytostatics' inhalation is rare; thus, air contamination has been poorly studied, with little improvement. Still, some elements of the analytical methods have not been extensively explored, namely: the amount of wetting solution, the extraction procedure, surface chemistry and roughness, recovery studies from specific surfaces, and cytostatics stability (in surfaces and during shipping and storage). Furthermore, complete validation data (including precision, accuracy, and instrumental and method detection limits) and estimation of global uncertainty are still lacking in most studies, thus preventing method comparison and proposal of standardized procedures.

Action and coping plans related to the behavior of adherence to oral anti-diabetic medication / Planos de ação e de enfrentamento de obstáculos relacionados ao comportamento de adesão aos antidiabéticos orais

ABSTRACT: Study Design: This mixed-methods study. Objective: To describe action plans related to the behavior of adher-ence to oral antidiabetic medications produced by people with type 2 diabetes mellitus and identify the challenges and coping strategies for the establishment of this behavior. Methods: The study followed-up 44 people with type 2 diabetes mellitus who used oral antidiabetic medications from southeast Brazil. Adults were invited to build action and coping plans based on the Implementation Intention Theory.The plans were quantitative and qualitatively ana-lyzed. Results: Action plans included three major themes: (1) binding oral antidiabetic medication to time markers or the sleep/wake cycle; (2) in specific environments; (3) associated with daily life activities. The motivation for coping with the perceived barriers focused on placing the pills in visible places, asking for help from family mem-bers, establishing a routine and feeding properly. Conclusions: The most effective way to manage satisfactory oral antidiabetic medication adherence seems to be recognizing the perceived barriers by patients. The implementation of specific and individualized action and coping plans to overcome perceived barriers was the stark difference. (AU)

RESUMO: Desenho do estudo: Estudo de método misto. Objetivo: Descrever planos de ação relacionados ao comportamento de adesão aos antidiabéticos orais elaborados por pessoas com diabetes mellitus tipo 2 e identificar as barreiras percebidas e respectivas estratégias de enfrentamento para efetivação desse comportamento. Métodos: O estudo envolveu 44 pessoas com diabetes mellitus tipo 2 que utilizavam antidiabéticos orais na região sudeste do Brasil. Adultos foram convidados a construir os planos de ação e de enfrentamento de obstáculos baseados sobre a Teoria da Ativação da Intenção. Os planos foram analisados quantitativa e qualitativamente. Resultados: Os planos de ação incluíram três temas principais: (1) Associar a tomada dos antidiabéticos orais aos marcadores de tempo ou ao ciclo de sono / vigília; (2) em ambientes específicos; (3) associados às atividades de vida diária. Os planos de enfrentamento das barreiras percebidas centraram-se em colocar os comprimidos em locais visíveis, pedir ajuda aos familiares para evitar esquecimento, estabelecer rotina e alimentar-se adequadamente. Conclusões: A forma mais eficaz de manejar a tomada de antidiabéticos orais de modo satisfatório parece ser o reconhecimento das barreiras percebidas pela própria pessoa. A implementação de ações específicas e individualizadas bem como de planos de enfrentamento para superar as barreiras percebidas foi o diferencial neste estudo. (AU)

Robertsonian rearrangements in Neotropical Meliponini karyotype evolution (Hymenoptera: Apidae: Meliponini).

Genome changes, evidenced through karyotype or nuclear genome size data, can result in reproductive isolation, diversification and speciation. The aim of this study was to understand how changes in the karyotype such as chromosome number and nuclear genome size accompanied the evolution of neotropical stingless bees, and to discuss these data in a phylogenetic context focusing on the karyotype evolution of this clade. We sampled 38 species representing the three Neotropical Meliponini groups; 35 for karyotype analyses and 16 for 1C value measurement. The chromosome number varied from 2n = 16 to 2n = 34, with distinct karyotypic formulae and the presence of a few polymorphisms, such as B chromosomes in one species and arm size differences between homologous chromosomes in two species. The mean 1C value varied from 0.31 pg to 0.92 pg. We associated empirical data on chromosome number and mean 1C value to highlight the importance of Robertsonian fusion rearrangements, leading to a decrease in chromosome number during the Neotropical Meliponini evolution. These data also allowed us to infer the independent heterochromatin amplification in several genera. Although less frequent, Melipona species with 2n = 22 represent evidence of Robertsonian fissions. We also pointed out the importance of chromosomal rearrangements that did not alter chromosome number, such as inversions and heterochromatin amplification.

PMS2: a potential prognostic protein marker in oral squamous cell carcinoma.

BACKGROUND: An increase in oral squamous cell carcinoma (OSCC) cases was observed despite the reduction in exposure to classic risk factors. Although the exact cause of this trend remains unknown, epigenetic factors could be contributing to an increased occurrence of these tumors. This study aims to assess the influence of PMS2 protein immunoexpression on the prognosis of patients with OSCC. MATERIAL AND METHODS: This study comprised 76 cases of OSCC treated between 2011 and 2016. Immunohistochemical staining for PMS2 was performed. For evaluation, 10 fields per histological section were photographed at a 400x magnification and positively-stained cells were counted with Image J. Mann-Whitney and Kruskal-Wallis tests were used to compare the immunolabeling pattern with the clinical-pathological and prognostic characteristics. Survival analysis was performed with Chi-square, Long-Rank Mantel-Cox and Cox regression tests (p<0.05). RESULTS: An overexpression of PMS2 was observed in N0/1 tumors and in oral cancers found in unusual locations. In patients ≤60 years of age, high levels of PMS2 (>60%; p=0.041) were associated with low survival (p=0.029). In multivariate analysis, surgery combined with chemotherapy (p=0.030) and high PMS2 immunoexpression (p=0.042) significantly increased the risk of death for ≤60 years old patients. CONCLUSIONS: The findings of this study indicate that PMS2 can be a potential prognostic protein marker in OSCC patients 60 years of age and younger.

Switching from originator recombinant growth hormone (Genotropin™) to biosimilar (CRISCY™): Results from a 6-month, multicentric, non-inferiority, extension trial.

OBJECTIVE: A previous 12-month comparative trial with Criscy™ (r-hGH Cristália), a biosimilar recombinant growth hormone, demonstrated equivalent efficacy and safety to Genotropin™. This extension trial evaluated the effects of switching patients treated with Genotropin™ to the biosimilar Criscy™ over an additional 6-month treatment period, comparing efficacy, safety, and immunogenicity parameters with patients remaining in the Criscy™ arm. DESIGN: This extension study included 11 research centers and 81 patients who participated in the CERES study (Czepielewski et al., 2019 [1]). Participants from the Genotropin™ arm (n = 39) had the drug replaced by Criscy™ and the remaining participants were kept in the Criscy™ arm (n = 42) for an additional 6-month period to evaluate immunogenicity, efficacy (growth rate, height SDS), and safety (laboratory tests, and adverse events). RESULTS: Before the switch, both Criscy™ and Genotropin groups were similar concerning demographics, and auxological measures: age, sex, height, height SDS, weight, and BMI. Height velocity (HV) after 18 months of treatment was 8.7 ± 1.56 cm/year for Criscy™ group and 8.9 ± 1.36 cm/year for Genotropin™ group in the ITT population (p = 0.43). The auxological parameters and IGF-1 and IGFBP-3 SDS were comparable between both groups of patients. No participants were excluded from the study due to adverse events. There were no clinical or statistical relevant differences between the treatment groups concerning frequency, distribution, intensity, and AEs outcome. Similarly, no new anti-r-hGH (ADA) cases among patients that switched from Genotropin™ to Criscy™ were reported. No neutralizing antibody (nAb) was detected in either group. CONCLUSIONS: This trial showed that switching from originator recombinant human growth hormone to Criscy™ had no impact on efficacy, safety, nor immunogenicity as compared to continued treatment with Criscy™. Growth rates and ADA incidence remained the same as seen before the switch.