Lymphoid interstitial pneumonia in a patient with systemic lupus erythematosus: Case report and literature review.

Lymphoid interstitial pneumonia (LIP) is a rare form of interstitial pulmonary disease, which has been described in association with a wide range of autoimmune disorders. Although the association of this entity with Sjogren's syndrome is well known, only a few cases are reported in relation to systemic lupus erythematosus (SLE). The aim of this paper is to review the cases reported in literature to date, as well as to describe the characteristics of these patients including the new case presented herein. We will be focusing on the case of a 36-year-old female patient diagnosed with SLE on hydroxychloroquine treatment who develops pleuritic chest pain and progressive dyspnea after 3 years of follow-up. The chest CT scan showed pleural thickening and both multiple and bilateral micronodules. A lung biopsy was also performed, revealing an infiltration of lymphocytes, plasma cells, and histiocytes in the alveolar septa suggestive of LIP. After conducting a review of the literature, we identified seven other cases describing SLE in association with LIP. The majority of them were young women, and LIP tends to appear early in the course of the disease, even as a form of initial presentation in some cases. Symptoms included cough, dyspnea, and pleuritic pain, with the exception of one case which was asymptomatic. It is noteworthy that half of the patients were positive for anti-SSA/anti-SSB autoantibodies, and some of them also met criteria for Sjogren's syndrome. Treatment with steroids and other immunosuppressive agents improved symptoms in all of them.

A relevant number of patients do not increase their engagement in physical, social and leisure activities at the medium-term after total knee arthroplasty: a prospective cohort study.

PURPOSE: The purpose of this study was to investigate the changes in engagement in physical, leisure and social activities in older adults following primary TKA. METHODS: A prospective study of 106 patients with a mean age of 72.6 (SD 7.4) years undergoing primary TKA was performed. Physical, social and leisure activities performed by the patients preoperatively and postoperatively at 3-year were recorded. Activities were selected according to the age, and grouped as passive, moderate and high intensity. The energy spent in each activity was expressed in Metabolic Equivalent of Task (MET) units. Charlson Comorbidity Index, Mini-mental test and Western Ontario and McMaster Universities (WOMAC) scores were also used. Multivariate analysis was used to identify predictors of active patients. RESULTS: Mean WOMAC significantly improved from preoperative (34.8, SD 11.8) to final follow-up (74.4, SD 11.1) (p = 0.001), and the mean energy spent increased from 10.7 (SD 13.6) to 28.2 (SD 16.2) MET-hour weekly (p = 0.001) with a decrease in the passive activities and increase in the moderate activities. However, the participation in high-intensity activities according to age was negligible. Only 65 (61.3%) patients were considered active postoperatively (weekly spending ≥ 40 MET), although the WOMAC scores were not significantly different between active and sedentary patients. Active patients compared with sedentary patients had a significant increase in engagement in physical, social and leisure activities, and a decrease in passive activities. Female gender (p = 0.037), less preoperatively participation in passive activities (p = 0.042), and greater participation in social activities (p = 0.027) were significant predictors of active patients at the final follow-up. CONCLUSION: Overall, most patients increased their activity level postoperatively. However, 38.6% of patients had no increased engagement in moderate physical, social or leisure activities at the medium-term despite improvements in pain and function provided by TKA. LEVEL OF EVIDENCE: II.

Synergy of carbohydrate and caffeine ingestion on physical performance and metabolic responses to exercise: A systematic review with meta-analysis.

Carbohydrates (CHO) and caffeine (CAF) are two ergogenic aids commonly used among athletes to enhance performance. However, there is some controversy as to whether the concurrent intake of both supplements might result in an additive and synergistic improvement in exercise performance. The aim of this systematic review and meta-analysis was to determine the effect of adding CAF to a protocol of CHO ingestion, compared with the intake of each ergogenic aid alone and with placebo, on exercise performance and metabolic responses in healthy young physically active adults. This study was conducted according to PRISMA 2020 guidelines. The PubMed, Web of Science, Medline Complete, CINAHL, SPORTDiscus and CENTRAL databases were searched including randomized controlled trials (RCT) that were at least single blind. The risk of bias assessment was performed using the Cochrane Risk-of-Bias tool 2. Meta-analysis were performed on performance variables and rating of perceived exertion (RPE) using the random-effects model. Thirteen RCT with 128 participants (117 men and 11 women) were included in this study. The ingestion of CAF and CHO reduced sprint time during repeated sprint protocols in comparison with CHO isolated ingestion (SMD: -0.45; 95% CI: -0.85, -0.05) while there was a tendency for a reduction in the time employed during time trials (SMD: -0.36; 95% CI: -0.77, 0.05). The RPE tended to be lower with CAF and CHO compared with CHO isolated ingestion during steady-state exercise (SMD: -0.43; 95% CI: -0.91, 0.05) with no differences between conditions in performance trials (SMD: -0.05, 95% CI: -0.39, 0.29). Although most of the studies showed higher values of blood glucose when CHO was co-ingested with CAF compared with PLA, only two studies observed higher values with CHO and CAF co-ingestion with respect to the isolated intake of CHO. One study observed greater fat oxidation and lower glycogen use when CAF was added to CHO. In terms of cortisol levels, one study showed an increase in cortisol levels when CAF was co-ingested with CHO compared with PLA. In summary, concurrent CHO and CAF intake may produce an additive ergogenic effect respect of the isolated ingestion of CHO. This additive effect was present when CHO was provided by a 6-9% of CHO solution (maltodextrin/dextrin + fructose) and CAF is administered in a dose of 4-6.5 mg/kg.

Similar outcomes and satisfaction after transtibial versus transportal femoral drilling for anterior cruciate ligament reconstruction in young adult recreational athletes.

PURPOSE: Controversy continues regarding whether the transtibial (TT) and transportal (TP) methods for anterior cruciate ligament (ACL) reconstruction provide similar or different outcomes, and the evidence on patient satisfaction is very limited. The objective of this study was to compare functional outcomes and patient satisfaction in young adult recreational athletes who underwent arthroscopic hamstring ACL reconstruction using either the TT or the TP femoral tunnel drilling method. METHODS: A nonrandomized prospective study was designed to compare the outcomes of arthroscopic hamstring ACL reconstruction using TT or TP method. Functional outcome was assessed with the Lyshom score, and patient satisfaction with a 5-point Likert scale. Knee stability was measured with the KT-1000 arthrometer. RESULTS: 42 patients in the TT group and 41 in TP group, with age ranged 18-40 years, were compared with a mean follow-up of 42 (range 24-60) months. There were no significant differences between groups in the Lysholm score (n.s.), sport return rate (n.s.) or patient satisfaction with the surgery (n.s.). Satisfaction was only significantly associated with the Lysholm score (OR 1.3; IC 95% 1.06-1.6; p = 0.012), but not with the return to sports (n.s.) or knee anterior laxity (n.s.). CONCLUSION: This study showed no statistical differences between the TT and the TP method in functional outcomes or patient satisfaction in young adult recreational athletes. In those patients, satisfaction with the surgery was not influenced by the return to sport activities. This study can guide surgeons in the decision-making for ACL reconstruction in recreational athletes. LEVEL OF EVIDENCE: Level II.

Varus alignment of the tibial component up to seven degrees is not associated with poor long-term outcomes in a neutrally aligned total knee arthroplasty.

PURPOSE: The purpose of this retrospective study was to evaluate the effect of varus alignment of the tibial component on the outcomes with a minimum follow-up of 10 years. The hypothesis was that varus alignment of the tibial component might not affect the outcomes and survival of a neutrally aligned primary TKA. METHODS: A matched case-control study was designed between 66 patients with varus alignment of the tibial component and 66 with neutral alignment with a minimum follow-up of 10 years. Functional outcome was assessed with the knee surgery scores (KSS) and reduced Western Ontario and MacMaster Universities questionnaire (WOMAC). Patient satisfaction was evaluated by a 0-10 visual analog scale. Radiological evaluation was performed at early postoperative and at final follow-up. RESULTS: The mean follow-up was 11.9 (SD 2.6) years for both groups. The mean postoperative proximal tibial angle in the varus group was 85.0° (SD 0.9) and 88.8° (SD 0.9) in control group. At the final follow-up, there were no significant differences in KSS, WOMAC, range of motion or patient satisfaction. There were no differences in the coronal anatomical alignment of the TKA between groups. Revision of TKA was performed in four knees in the varus group, and one in control group, due to aseptic loosening of the tibial component in all cases. TKA survival at 10 years was not significantly different between groups. CONCLUSION: The alignment of the tibial component up to 7° varus did not negatively affect implant survival, patient satisfaction, and function of a well-aligned TKA, with a minimum postoperative follow-up of 10 years. LEVEL OF EVIDENCE: III.

V-Y turndown flap augmentation for acute quadriceps rupture after total knee arthroplasty: a prospective matched cohort study.

PURPOSE: To evaluate the effectiveness of the quadriceps V-Y turndown augmentation for acute quadriceps tendon ruptures in the setting of TKA. METHODS: Prospective cohort of 22 patients with quadriceps rupture after TKA were compared with 44 matched patients underwent TKA without quadriceps rupture. Quadriceps ruptures were treated within three weeks after injury by suture augmented with Scuderi quadriceps V-Y turndown flap. Clinical evaluation was performed by the Knee Society Scores (KSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and range of motion. Patellar height was assessed by the Blackburne-Peel ratio. RESULTS: The mean follow-up was 3.3 (range, 3-4) years. At the final follow-up, there were significant improvements in mean KSS scores in both groups (p = 0.001). In the quadriceps group, the mean flexion for all patients, but one with arthrodesis for periprosthetic infection, was 100.1° (range, 90-110°) and mean extensor lag was 7.1° (range, 0-20°). There were significant differences between groups in KSS scores (p = 0.001). Active flexion (p = 0.020) and extension (p = 0.001) were significantly better in the control group. However, there was no significant difference in WOMAC scores (p = 0.252) or patient satisfaction (p = 0.352). There were no quadriceps reruptures. One patient with periprosthetic infection was treated with arthrodesis. CONCLUSION: The quadriceps V-Y turndown is an effective and safe procedure for quadriceps ruptures in the setting of TKA. Although the functional outcomes were lower than in TKA patients with no quadriceps rupture, the quality of life and satisfaction were successful in the TKA patients with quadriceps rupture.

Association between perceived level of stress, clinical characteristics and psychopathological symptoms in women with systemic lupus erythematosus.

OBJECTIVES: To evaluate psychopathological status and stress level from a sample with SLE; compare mental functioning and stress levels between women with SLE and healthy women; determine whether disease duration, disease activity, cumulative organ damage and stress have an influence on psychopathological symptoms in SLE patients; and evaluate whether perception of stress is related to SLE severity. METHODS: We conducted a cross-sectional study of 425 participants; 202 women with SLE, with an average age (SD) of 36.61 (10.15), and 223 healthy women, with age-matched controls. The assessment included the clinical characteristics (disease duration, SLE activity, cumulative organ damage, pharmacotherapy), the Symptom Checklist-90-Revised (SCL-90-R) and the Perceived Stress Scale. Descriptive, comparative, univariate and multivariate analysis were performed. RESULTS: SLE patients showed psychopathological alterations in the somatisation, obsessive-compulsive and positive discomfort subscales of SCL-90-R. Women with SLE reported significantly higher scores on the psychopathological dimensions and perceived stress compared to healthy women, except for paranoid ideation. Disease duration, SLE activity, cumulative organ damage, and perceived stress were shown to be significant predictors of psychopathological manifestations, explaining a range, between 20 and 43%, of variance across SCL-90-R dimensions. Moreover, perceived stress was related to SLE activity, after controlling for psychopathological dimensions. CONCLUSIONS: The psychopathological manifestations in SLE appeared to be influenced by perceived stress, disease duration, disease activity and cumulative organ damage. In turn, perceived stress was associated with disease severity. This knowledge may contribute to a more comprehensive perspective of these manifestations in the SLE population in the clinical setting.

The Sensitive Period for Tactile Remapping Does Not Include Early Infancy.

Visual input during development seems crucial in tactile spatial perception, given that late, but not congenitally, blind people are impaired when skin-based and tactile external representations are in conflict (when crossing the limbs). To test whether there is a sensitive period during which visual input is necessary, 14 children (age = 7.95) and a teenager (LM; age = 17.38) deprived of early vision by cataracts, and whose sight was restored during the first 5 months and at age 7, respectively, were tested. Tactile localization with arms crossed and uncrossed was measured. Children showed a crossing effect indistinguishable from a control group (Ns = 28, age = 8.24), whereas LM showed no crossing effect (Ns controls = 14, age = 20.78). This demonstrates a sensitive period which, critically, does not include early infancy.

Identification of underlying and transfusion-related platelet qualitative alterations in the hemato-oncologic patient.

Hemato-oncologic patients with chemotherapy-induced thrombocytopenia are one of the populations receiving platelet transfusions. The general practice with these patients is to give prophylactic platelet transfusions when platelet counts fall below 10×109PLT/L. However, in more than 40% of these patients, platelet transfusion does not prevent bleeding. The reason of the low efficacy of platelet transfusion in the context of chemotherapy patients is not entirely understood. We therefore aimed at immunophenotyping the expression of platelet surface and activation markers and thrombopoietin levels from hemato-oncologic patients before and after transfusion. A more detailed follow-up was performed in three patients that underwent autologous bone marrow transplantation. As previously reported, basal platelet activation was observed in hemato-oncologic patients. Based on flow cytometry parameters, i.e. the percentage of positivity and mean fluorescence intensity (MFI) distribution, our data provide an additional interpretation of platelet acquired qualitative changes in the hemato-oncologic patient. From our results we propose: first, the underlying activation of platelets in the hemato-oncologic patient is accompanied by loss of expression of the platelet receptors that are susceptible to protease-mediated shedding; second, soon after transfusion, the newly circulating donor platelets show additional activation, which may result in subsequent platelet receptor recycling and potential accelerated clearance of these activated platelets. In conclusion, the immunophenotype of circulating platelets changes after prophylactic platelet transfusion. Next to platelet count increment, exploration of this immunophenotype might help to explain transfusion refractory bleeding in hemato-oncologic patients. Eventually this may lead to personalization and improvement of the present platelet transfusion support regime.

Octadecyl-viologen Photooxidation in Surface Films: Macroscopic Contraction of Langmuir Monolayer by UV Irradiation.

The effects of UV radiation on a viologen derivative, octadecylviologen (OV), in Langmuir monolayers at the air-aqueous solution interface and in Langmuir-Blodgett (LB) films have been investigated. Langmuir monolayers suffer a sharp contraction after UV irradiation, clearly visible by the drop in surface pressure or the loss of surface area observed in the surface pressure-area isotherms. The UV-vis reflection measurements reveal a deep change in the OV monolayer caused by a photochemical reaction, which suggests the pyridones formation as photoreaction products. LB films (Z type), before and after being irradiated with UV light, have been studied by using UV-vis absorption and infrared and X-ray photoelectron spectroscopy. The results confirm that after the photodegradation of the viologen films, the presence of oxygen results in the appearance of pyridones as reaction products. This article demonstrates that, in the absence of catalysts, the photooxidation of viologen surface films occurs only under a particular molecular organization imposed by the air-water interface.

UV-Vis reflection spectroscopy under variable angle incidence at the air-liquid interface.

The UV-Vis reflection spectroscopy (UV-Vis-RS) in situ at the air-liquid interface provides information about tilt and aggregation of chromophores in Langmuir monolayers. This information is particularly important given in most cases the chromophore is located at the polar region of the Langmuir monolayer. This region of the Langmuir monolayers has been hardly accessible by other experimental techniques. In spite of its enormous potential, the application of UV-Vis-RS has been limited mainly to reflection measurements under light normal incidence or at lower incidence angles than the Brewster angle. Remarkably, this technique is quite sensitive to the tilt of the chromophores at values of incidence angles close to or larger than the Brewster angle. Therefore, a novel method to obtain the order parameter of the chromophores at the air-liquid interface by using s- and p-polarized radiation at different incidence angles is proposed. This method allowed for the first time the experimental observation of the two components with different polarization properties of a single UV-Vis band at the air-liquid interface. The method of UV-Vis spectroscopy under variable angle incidence is presented as a new tool for obtaining rich detailed information on Langmuir monolayers.

Very accelerated partial breast irradiation in 1 or 2 days: Late toxicity and early oncological outcome of the GEC-ESTRO VAPBI cohort.

PURPOSE: To analyze late toxicity after very accelerated partial breast irradiation (VAPBI) for low-risk breast cancer. MATERIALS: Methods: In this retrospective, observational, international multicenter study (HDH F20220713143949), patients with low-risk breast cancer underwent lumpectomy + vAPBI (high-dose rate multicatheter interstitial brachytherapy-MIBT). VAPBI was performed with 4(4x6.2 Gy/2d), 3(3x7.45 Gy/2d) or 1 fraction (1x16Gy or 1x18Gy/1d). Primary endpoint was late toxicity. Secondary endpoints were cumulative incidence of breast cancer local relapse (LR) and distant metastatic relapse (DMR) and specific (SS) and overall (OS) survivals. Prognostic factors for late toxicity were analyzed. RESULTS: From 01/2012 to 06/2022, 516 pts with early breast cancer were enrolled. Median follow-up was 44 months [95 %CI 39-46]. Median age was 71 years [40-100]. Median tumor size was 12 mm [1-35]. VAPBI delivered 1, 3 and 4 fractions for 205pts (39.7 %), 167pts (32.4 %) and 144pts (28 %) respectively. 221 late toxicity events were observed in 168pts (32.6 %) (Fibrosis, dyschromia, pain and telangiectasia). Grade 2 and 3 late toxicities were observed in 7.2 and 0.6 % respectively (no G4) with no difference between 1 and ≥ 2 treatment days. CTV > 50 cc (p = 0.007) and V150 > 40 % (p = 0.027) were prognostic factors for G ≥ 2 late toxicity. Four-year cumulative incidence rates of LR and DMR were 2 % [95 %CI 0-3] and 1 % [95 %CI 0-2] respectively. CONCLUSIONS: VAPBI based on 1 or ≥ 2 days of MIBT represents an attractive de-escalation of irradiation approach for low-risk breast cancer. Late toxicity profile appears acceptable while early oncological outcome shows encouraging local control. Longer follow-up is warranted in order to confirm these preliminary results.

Post- versus intra-operative implant for breast cancer interstitial brachytherapy: How to choose?

Purpose: Breast brachytherapy (BB) represents an important radiation therapy modality in modern breast cancer treatments. Currently, BB is mainly used for accelerated partial breast irradiation (APBI), local boost after whole breast radiation therapy (WBRT), and as salvage re-irradiation after second lumpectomy (APBrl). Two multi-catheter interstitial brachytherapy (MIB) techniques can be offered: intra-operative (IOB) and post-operative (POB) brachytherapy. The aim of this article was to summarize current available data on these two different brachytherapy approaches for breast cancer. Material and methods: A literature search was performed, and different experiences published by BB expert teams were analyzed and compared. These two different brachytherapy approaches for breast cancer have also been presented and discussed during meetings of the GEC-ESTRO BCWG. In addition, expert recommendations were defined. Results: A comprehensive description and practical comparison of both the techniques, i.e., IOB and POB, considering the latest available published data were presented. Different technical, logistic, and clinical aspects of both the methods were thoroughly examined and analyzed. This detailed comparison of the two breast brachytherapy techniques was supported by scientific data from extensive experience of experts, facilitating an objective analysis that, to our knowledge, has not been previously published. Conclusions: Based on the comprehensive analysis of both the brachytherapy techniques available, this article serves as a valuable resource to guide breast teams in selecting the optimal BB technique (POB or IOB), considering hospital environment, multi-disciplinary collaboration, and patient logistics.

Economic impact of immunoglobulin replacement therapy in secondary immunodeficiency to hematological cancer: a single center observational study.

This is the first report of the health economic benefits derived from preventing infections through Immunoglobulin Replacement Therapy (IgRT) in patients with secondary immunodeficiency due to hematological malignancies. We conducted a retrospective population-based cohort study using patient medical history and pharmacy data from the Hospital Clínico San Carlos for 21 patients between 2011 and 2020. The pharmacoeconomic impact of using prophylactic IgRT was assessed by comparing characteristics of the SID patients 1 year before and after initiating IgRT measured by direct medical and tangible indirect costs. Results indicate a marked reduction in hospitalization days following IgRT initiation, decreasing from an average of 13.9 to 6.1 days per patient, with the elimination of ICU admissions. While emergency department visits decreased significantly, the number of routine consultations remained unchanged. Notably, absenteeism from work dropped substantially. The financial analysis revealed significant reductions in medication use and fewer ancillary tests, resulting in considerable cost savings. Specifically, total expenditure dropped from €405,088.18 pre-IgRT to €295,804.42 post-IgRT-including the cost of IgRT itself at €156,309.60. Overall, the annual savings amounted to €109,283.84, validating the cost-effectiveness of IgRT in managing SID in patients with hematological cancers.

Oridonin from Rabdosia rubescens: An emerging potential in cancer therapy - A comprehensive review.

Cancer incidences are rising each year. In 2020, approximately 20 million new cancer cases and 10 million cancer-related deaths were recorded. The World Health Organization (WHO) predicts that by 2024 the incidence of cancer will increase to 30.2 million individuals annually. Considering the invasive characteristics of its diagnostic procedures and therapeutic methods side effects, scientists are searching for different solutions, including using plant-derived bioactive compounds, that could reduce the probability of cancer occurrence and make its treatment more comfortable. In this regard, oridonin (ORI), an ent-kaurane diterpenoid, naturally found in the leaves of Rabdosia rubescens species, has been found to have antitumor, antiangiogenesis, antiasthmatic, antiinflammatory, and apoptosis induction properties. Extensive research has been performed on ORI to find various mechanisms involved in its anticancer activities. This review article provides an overview of ORI's effectiveness on murine and human cancer populations from 1976 to 2022 and provides insight into the future application of ORI in different cancer therapies.

Long-term results of intraoperative multicatheter breast implant (IOMBI) for accelerated partial breast irradiation (APBI) on early breast cancer patients.

BACKGROUND AND PURPOSE: Multicatheter breast brachytherapy is a standard technique for accelerated partial breast irradiation (APBI) in early breast cancer patients. Intraoperative multicatheter breast implant (IOMBI) followed by perioperative high-dose-rate brachytherapy (PHDRBT) offers a novel and advantageous approach. We present long-term oncological, toxicity, and cosmesis outcomes for a well-experienced single institution. MATERIALS AND METHODS: Eligible women aged ≥ 40 years with clinically and radiologically confirmed unifocal invasive or in situ ≤ 3 cm breast tumors underwent IOMBI during breast-conserving surgery. Patients meeting APBI criteria by definitive pathologic results received 3.4 Gy × 10fx with PHDRBT. Patients not suitable for APBI received PHDRBT-boost followed by WBRT. RESULTS: A total of 171 patients underwent IOMBI during BCS, 120 patients (70.1 %) were suitable for APBI and 51 (29.8 %) for anticipated PHDRBT-boost. The median age was 61 years (range: 40-78), the median tumor size was 1.1 cm (range: 0.2-3.5), with a histological diagnosis of invasive ductal carcinoma in 78.9 % and ductal in situ in 21.1 %. A median of 9 catheters (range: 4-14) were used. For APBI, the median CTV and V100 were 40.8 cc (range: 8.6-99) and 35.4 cc (range: 7.2-94). The median of healthy breast tissue irradiated represents 7.2 % (range: 2.3-28 %) and the median local treatment duration was 10 days (range: 7-16). With a median follow-up of 8.8 years (range: 0.3-16.25), the 8-year local, locoregional, and distant control rates were 99 %, 98.1 %, and 100 %. G1-G2 late-toxicity rate was 53.4 %. Long-term cosmetic evaluation was excellent-good in 90.8 %. CONCLUSION: IOMBI&PHDRBT program reports excellent long-term oncological outcomes, with a reduction from unnecessary irradiation exposure which translates into low long-term toxicity and good cosmesis outcomes, especially on well-selected APBI patients.

Retinal hemorrhages due to intracranial hypertension, is it possible to differentiate them from those associated with abuse?

BACKGROUND: Retinal hemorrhages (RHs) are suggestive of abusive head trauma (AHT). Even so, controversy persists about other possible causes, a fact that hinders the diagnosis of abuse. OBJECTIVE: To determine the prevalence and patterns of RHs associated with increased intracranial pressure (ICP) in young children. PARTICIPANTS AND METHODS: Prospective, single center study of children aged 29 days-3 years undergoing a lumbar puncture with opening pressure (OP) measured during routine clinical care in the emergency department, over a 4-year period. Children with known causes of RHs were excluded. All the children underwent a detailed ophthalmological examination within 72 h of admission. For children with RHs, an in-depth investigation was carried out to rule out AHT. RESULTS: Thirty-four patients were included: 20(58.8 %) were boys, median age 11.7 months (range 1-33 months). Overall, 29(85.3 %) had clinical findings of increased ICP. The duration of symptoms was ≤4 days in all patients except one, in whom it was 1.5 months. The median OP was 27cmH2O (range 20-60cmH2O). One of the children was found to have RHs, with evaluation resulting in a diagnosis of AHT. No RHs were found in any of the others studied. Using the Wilson method, we can be confident to an upper limit of 95 % that the probability of RHs occurring secondary to increased ICP alone is at most 0.1. CONCLUSIONS: RHs were not detected in patients with isolated nontraumatic increased ICP, measured via OP and diagnosed in the ED. Therefore, if RHs are detected, investigation into the possibility of AHT is warranted.

Regulatory aspects of a nanomaterial for imaging therapeutic cells.

The ability to track therapeutic cells upon administration to the patient is of interest to both regulators and developers of cell therapy. The European Commission Horizon2020 project nTRACK from 2017-2022 aimed to develop a multi-modal nano-imaging agent to track therapeutic cells during development of a cell therapy. As part of this project, we investigated the regulatory pathway involved for such a product if marketed as a stand-alone product. An important regulatory hurdle appeared to be the appropriate regulatory classification of the nTRACK nano-imaging agent, as neither the definition for medicinal product nor the definition for medical device appeared to be a good fit for the purpose of the product and we were confronted with diverging views of competent authorities on the classification. As a consequence, the information requirements to fulfill before conducting a First in Human trial are not evident and can only be decided upon by closely collaborating and communicating with the relevant authorities throughout the development of the product. Moreover, standard test methods for demonstrating the quality and safety of a medicinal product or medical device are not always suitable for nanomaterials such as the nTRACK nano-imaging agent. Regulatory agility is therefore a great need to prevent delay of promising medical innovations, although regulatory guidance on these products will likely improve with more experience. In this article, we outline the lessons learnt related to the regulatory process of the nTRACK nano-imaging agent for tracking therapeutic cells and offer recommendations to both regulators and developers of similar products.

A Comprehensive Review of the Effect of Honey on Human Health.

Honey is a nutritious, healthy, and natural food, to which antioxidant, anti-inflammatory, and antimicrobial properties have been attributed, mainly due to its content of phenolic compounds. The aim of this review is to analyze the available evidence of the effect of honey on humans. Forty-eight clinical trials published between 1985 and 2022 were analyzed, with a total of 3655 subjects. More beneficial effects of honey intake than no or negative effects on different cardiovascular and metabolic risk factors, glucose tolerance, mucositis caused by chemo-radiotherapy, cough in children and wound healing, among others have been observed. Although the number of studies conducted to date is limited and the different investigations are not standardized, beneficial effects of honey intake have been observed, especially when its intake replaces the intake of other sweeteners. In addition, honey could be a safe adjuvant to be administered alongside drugs used for certain diseases.

Added Sugar Consumption in Spanish Children (7-12 y) and Nutrient Density of Foods Contributing to Such Consumption: An Observational Study.

BACKGROUND: Diets rich in free sugars are associated with an increased risk of obesity. The aim of the present study is to estimate the intake of added sugars in the population of Spanish children and analyze the quality of the foods that contribute to this intake. METHODS: An observational study was conducted to collect self-reported information on weekly food consumption in 1775 Spanish children (7-12 years). Nutrient contents were obtained from different databases. Two nutritional density indices were constructed taking into account all nutrients provided and compared with two previously described indices. RESULTS: The average consumption of added sugars in Spanish children was 55.7 ± 1.0 g/day. The products that most contributed to added sugar intake were biscuits (13.3%), cocoa powder (11.1%), sweetened yogurts (9.9%), and dairy desserts (8.6%). Among these, dairy products had considerable nutritional value. Parents' perception of nutritional value was not aligned with the actual nutritional value. CONCLUSION: The consumption of added sugars was higher than recommended. Public awareness efforts should focus on: (1) the reduction of consumption of low-nutritional quality products containing high amounts of added sugars; (2) the industrial reformulation of most consumed products to reduce sugar content and increase valuable nutrients; and (3) nutritional education.