A novel TAp73-inhibitory compound counteracts stemness features of glioblastoma stem cells.

Glioblastoma (GB) is the most common and fatal type of primary malignant brain tumor for which effective therapeutics are still lacking. GB stem cells, with tumor-initiating and self-renewal capacity, are mostly responsible for GB malignancy, representing a crucial target for therapies. The TP73 gene, which is highly expressed in GB, gives rise to the TAp73 isoform, a pleiotropic protein that regulates neural stem cell biology; however, its role in cancer has been highly controversial. We inactivated TP73 in human GB stem cells and revealed that TAp73 is required for their stemness potential, acting as a regulator of the transcriptional stemness signatures, highlighting TAp73 as a possible therapeutic target. As proof of concept, we identified a novel natural compound with TAp73-inhibitory capacity, which was highly effective against GB stem cells. The treatment reduced GB stem cell-invasion capacity and stem features, at least in part by TAp73 repression. Our data are consistent with a novel paradigm in which hijacking of p73-regulated neurodevelopmental programs, including neural stemness, might sustain tumor progression, pointing out TAp73 as a therapeutic strategy for GB.

Clinical Results of a Monofocal Aspheric Bitoric Intraocular Lens with Plate Haptics in Hyperopic Eyes.

Purpose: To assess the refractive and visual outcomes of hyperopic and astigmatic eyes implanted with a monofocal, aspheric, bitoric intraocular lens (IOL) with plate haptics following cataract surgery. Methods: The study evaluated 51 eyes implanted with the AT TORBI 709M IOL (Carl Zeiss Meditec AG, Jena, Germany) during a follow-up of 12-months. Refractive error, rotational stability, monocular uncorrected distance visual acuity (UDVA), monocular corrected distance visual acuity (CDVA), and contrast sensitivity were analyzed at 1-, 6-, and 12-months post-surgery. Results: At 12 months, the cumulative CDVA was 20/25 in 94.12% of eyes and 20/32 or better in 98.04%. The UDVA was the same as, or better than, the CDVA in 88.24% of eyes. The mean logMAR UDVA and CDVA values were 0.06 ± 0.11 and 0.00 ± 0.08, respectively. In addition, 92.16% of eyes were within ±0.50 D and 98.04% were within ±1.00 D of a spherical equivalent, and 86.27% of eyes had refractive astigmatism ≤0.50D and 100% were ≤1.00D. The mean spherical equivalent was 0.21 ± 0.31D and the mean refractive cylinder 0.34 ± 0.27D. The IOL rotation was 1.18 ± 1.35 degrees and all eyes had a rotation ≤5 degrees. The log contrast sensitivity functions were good and similar for all spatial frequencies during follow-up. Conclusion: Our results demonstrate that implantation of the AT TORBI 709M IOL in hyperopic and astigmatic eyes is effective and safe. The visual and refractive outcomes were good, showing excellent rotational stability.

Oviductal extracellular vesicles miRNA cargo varies in response to embryos and their quality.

BACKGROUND: Increasing evidence points to an active role of oviductal extracellular vesicles (oEVs) in the early embryo-maternal dialogue. However, it remains unclear whether oEVs contribute to the recognition of the presence of embryos and their quality in the oviduct. Hence, we examined whether the molecular cargo of oEVs secreted by bovine oviduct epithelial cells (BOEC) differs depending on the presence of good (≥ 8 cells, G) or poor (< 8 cells, P) quality embryos. In addition, differences in RNA profiles between G and P embryos were analyzed in attempt to distinguish oEVs and embryonic EVs cargos. METHODS: For this purpose, primary BOEC were co-cultured with in vitro produced embryos (IVP) 53 h post fertilization as follows: BOEC with G embryos (BGE); BOEC with P embryos (BPE); G embryos alone (GE); P embryos alone (PE); BOEC alone (B) and medium control (M). After 24 h of co-culture, conditioned media were collected from all groups and EVs were isolated and characterized. MicroRNA profiling of EVs and embryos was performed by small RNA-sequencing. RESULTS: In EVs, 84 miRNAs were identified, with 8 differentially abundant (DA) miRNAs for BGE vs. B and 4 for BPE vs. B (P-value < 0.01). In embryos, 187 miRNAs were identified, with 12 DA miRNAs for BGE vs. BPE, 3 for G vs. P, 8 for BGE vs. GE, and 11 for BPE vs. PE (P-value < 0.01). CONCLUSIONS: These results indicated that oEVs are involved in the oviductal-embryo recognition and pointed to specific miRNAs with signaling and supporting roles during early embryo development.

Treatment outcomes in patients with large B-cell lymphoma after progression to chimeric antigen receptor T-cell therapy.

Over 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients who receive chimeric antigen receptor (CAR) T cells will experience disease progression. There is no standard next line of therapy and information in this setting is scarce and heterogeneous. We analyzed 387 R/R LBCL patients who progressed after CAR T cells from July 2018 until March 2022 in Spain and the United Kingdom. Median overall survival (OS) was 5.3 months, with significant differences according to the interval between infusion and progression (<2 months [1.9 months], 2-6 months [5.2 months], and >6 months [not reached]). After progression, 237 (61%) patients received treatment. Focusing on the first subsequent therapy, overall (complete) response rates were 67% (38%) for polatuzumab-bendamustine-rituximab (POLA), 51% (36%) for bispecific antibodies (BsAb), 45% (35%) for radiotherapy (RT), 33% (26%) for immune checkpoint inhibitors (ICIs), 25% (0%) for lenalidomide (LENA), and 25% (14%) for chemotherapy (CT). In terms of survival, 12-month progression-free survival and OS was 36.2% and 51.0% for POLA, 32.0% and 50.1% for BsAb, 30.8% and 37.5% for RT, 29.9% and 27.8% for ICI, 7.3% and 20.8% for LENA, and 6.1% and 18.3% for CT. Thirty-two (14%) patients received an allogeneic hematopoietic cell transplant with median OS not reached after a median follow-up of 15.1 months. In conclusion, patients with R/R LBCL who progress within the first 2 months after CAR T-cell therapy have dismal outcomes. Novel targeted agents, such as polatuzumab and BsAbs, can achieve prolonged survival after CAR T-cell therapy failure.

Gender, smoking, and tobacco cessation with pharmacological treatment in a cluster randomized clinical trial.

INTRODUCTION: Whether men find it easier to quit smoking than women is still controversial. Different studies have reported that the efficacy of pharmacological treatments could be different between men and women. This study conducted a secondary analysis of 'Subsidized pharmacological treatment for smoking cessation by the Spanish public health system' (FTFT-AP study) to evaluate the effectiveness of a drug-funded intervention for smoking cessation by gender. METHODS: A pragmatic randomized clinical trial by clusters was used. The population included smokers aged ≥18 years, smoking >10 cigarettes per day, randomly assigned to an intervention group receiving regular practice and financed pharmacological treatment, or to a control group receiving only regular practice. The main outcome was continued abstinence at 12 months, self-reported and validated with CO-oximetry. The percentage, with 95% confidence intervals, of continued abstinence was compared between both groups at 12 months post-intervention, by gender and the pharmacological treatment used. Multilevel logistic regression analysis was performed. RESULTS: A total of 1154 patients from 29 healthcare centers were included. The average age was 46 years (SD=11.78) and 51.7% were men. Overall, the self-reported abstinence at 12 months was 11.1% (62) in women and 15.7% (93) in men (AOR=1.4; 95% CI: 1.0-2.0), and abstinence validated by CO-oximetry was 4.6% (26) and 5.9% (35) in women and men, respectively (OR=1.3; 95% CI: 0.7-2.2). In the group of smokers receiving nicotine replacement treatment, self-reported abstinence was higher in men compared to women (29.5% vs 13.5%, OR=2.7; 95% CI: 1.3-5.8). CONCLUSIONS: The effectiveness of a drug-financed intervention for smoking cessation was greater in men, who also showed better results in self-reported abstinence with nicotine replacement treatment.

Sperm exposure to accessory gland secretions alters the transcriptomic response of the endometrium in cattle.

In cattle, mating to intact, but not vasectomised, bulls has been shown to modify the endometrial transcriptome, suggesting an important role of sperm in the modulation of the uterine environment in this species. However, it is not clear whether these changes are driven by intrinsic sperm factors, or by factors of accessory gland (AG) origin that bind to sperm at ejaculation. Therefore, the aim of the present study was to determine whether ejaculated sperm, which are suspended in the secretions of the AGs, elicit a different endometrial transcriptomic response than epididymal sperm, which have never been exposed to AG factors. To this end, bovine endometrial explants collected from heifers in oestrus were (co-)incubated for 6 h alone (control), or with epididymal sperm or ejaculated sperm, following which transcriptomic changes in the endometrium were evaluated. Epididymal sperm elicited a more dramatic endometrial response than ejaculated sperm, in terms of the number of differentially expressed genes (DEGs). Indeed, RNA-sequencing data analysis revealed 1912 DEGs in endometrial explants exposed to epididymal sperm compared with control explants, whereas 115 DEGs were detected between endometrial explants exposed to ejaculated sperm in comparison to control explants. The top pathways associated with genes upregulated by epididymal sperm included T cell regulation and TNF, NF-KB and IL17 signalling. Interestingly, ejaculated sperm induced downregulation of genes associated with T cell immunity and Th17 differentiation, and upregulation of genes involved in NF-KB signalling, in comparison to epididymal sperm. These data indicate that factors of AG origin modulate the interaction between sperm and the endometrium in cattle.

Clinical Outcomes of a Monofocal, Optimized, Aspheric, Hydrophobic Acrylic Intraocular Lens Implant.

Purpose: To evaluate the refractive and visual outcomes of eyes implanted with monofocal, optimized, aspheric, hydrophobic acrylic intraocular lenses (IOL) following cataract surgery. Methods: The study assessed 55 eyes implanted with CT LUCIA® 621P IOLs (Carl Zeiss Meditec AG, Jena, Germany) at 3-months postsurgery. The main outcome measures were refractive error, monocular corrected distance visual acuity (CDVA), monocular uncorrected distance visual acuity (UDVA), photopic and mesopic contrast sensitivity, and wavefront aberrations. Patients were asked to complete the Catquest-9SF questionnaire. Results: At 3 months, the cumulative Snellen visual acuity was 20/20 in 94.55% of eyes and 20/25 or better in 100%. The difference between the UDVA and CDVA was either the same (70.91%) or better (29.09%) in all eyes. The mean Snellen decimal UDVA and DCVA were 1.07 ± 0.15 and 1.13 ± 0.11, respectively. The safety and efficacy indexes were 1.48 and 1.40, respectively. 47.27% of eyes showed a spherical equivalent ±0.13 D, with 92.73% of the eyes were within ±0.50 D and all eyes were within ±1.00 D. The mean spherical equivalent was -0.03 ± 0.30 D and the mean refractive cylinder -0.36 ± 0.34 D. The log photopic and mesopic contrast sensitivity functions were good and similar for all spatial frequencies. All patients reported being either fairly satisfied (score 3) or very satisfied (score 4) with their vision (mean = 3.64 ± 0.49). No intra- and postoperative complications were reported during the 3 months of follow-up. Conclusion: The current study demonstrates that excellent visual and refractive outcomes, as well as patient satisfaction, can be achieved after cataract surgery with optimized, aspheric CT LUCIA 621P monofocal IOLs.

Improving anaemia diagnosis using peripheral blood smear with remote interpretation in adults living with HIV with moderate to severe anaemia: A prospective study nested within the Kilombero and Ulanga antiretroviral cohort.

INTRODUCTION: In low-resource settings, anaemia is a very common condition. Identification of anaemia aetiologies remains challenging due to the lack of diagnostic tools and expertise. We aimed to improve anaemia diagnostics using peripheral blood smear (PBS) with remote interpretation in people living with HIV (PLHIV) with moderate to severe anaemia. METHODS: We conducted a prospective study nested within the Kilombero and Ulanga Antiretroviral Cohort, including non-pregnant PLHIV aged ≥18 years presenting with moderate (haemoglobin 7.0-9.9 g/dl) or severe (<7.0 g/dl) anaemia at any visit from January 2019 to December 2020. For each participant, ten PBS images, full blood count and clinical details were shared with a haematologist for remote interpretation (enhanced care). Identification of anaemia etiologies and potential impact on treatment was compared between enhanced and standard care. RESULTS: Among 400 PLHIV with moderate to severe anaemia, 349 (87%) were female, median age was 40 years (interquartile range (IQR) 35-46)), 65 (17%) had a body mass index <18.5 kg/m2, 215 (54%) had HIV WHO stage III/IV, 79 (20%) had a CD4 cell count <200 cells/µl and 317 (89%) had HIV viral load <100 copies/ml. Severe anaemia was diagnosed in 84 (21%). Suspected multiple aetiologies were documented more frequently by enhanced care compared to standard care 267 (67%) vs 20 (5%); p<0.001. Suspected iron deficiency was the most frequent aetiology (n = 337; 84%), followed by chronic disease (n = 199; 50%), folate/vitamin B12 deficiency (n = 78; 20%) and haemoglobinopathy (n = 83; 21%). In 272 participants (68%), enhanced care revealed additional clinically relevant findings with impact on the treatment recommendation. CONCLUSION: Remote interpretation of PBS combined with clinical information and blood cell count results can provide insights to the suspected aetiological diagnosis of moderate and severe anaemia in rural low-resource settings and impact specific treatment.

Maternal blood transcriptome as a sensor of fetal organ maturation at the end of organogenesis in cattle†.

Harnessing information from the maternal blood to predict fetal growth is attractive yet scarcely explored in livestock. The objectives were to determine the transcriptomic modifications in maternal blood and fetal liver, gonads, and heart according to fetal weight and to model a molecular signature based on the fetal organs allowing the prediction of fetal weight from the maternal blood transcriptome in cattle. In addition to a contemporaneous maternal blood sample, organ samples were collected from 10 male fetuses at 42 days of gestation for RNA-sequencing. Fetal weight ranged from 1.25 to 1.69 g (mean = 1.44 ± 0.15 g). Clustering data analysis revealed clusters of co-expressed genes positively correlated with fetal weight and enriching ontological terms biologically relevant for the organ. For the heart, the 1346 co-expressed genes were involved in energy generation and protein synthesis. For the gonads, the 1042 co-expressed genes enriched seminiferous tubule development. The 459 co-expressed genes identified in the liver were associated with lipid synthesis and metabolism. Finally, the cluster of 571 co-expressed genes determined in maternal blood enriched oxidative phosphorylation and thermogenesis. Next, data from the fetal organs were used to train a regression model of fetal weight, which was predicted with the maternal blood data. The best prediction was achieved when the model was trained with 35 co-expressed genes overlapping between heart and maternal blood (root-mean-square error = 0.04, R2 = 0.93). In conclusion, linking transcriptomic information from maternal blood with that from the fetal heart unveiled maternal blood as a predictor of fetal development.

Granulocytic Sarcoma Mimicking Cholesteatoma: Beware the Temporal Bone in Haematological Patients.

Granulocytic sarcoma is a myeloid neoplasm that can occur in isolation or in association with acute leukaemia. The temporal bone represents a sanctuary site for myeloid progenitors: granulocytic sarcoma may develop in this location before or concomitantly with the onset of acute leukaemia. This atypical presentation with clinical and radiological data that closely mimic those of cholesteatoma often delays an accurate diagnosis. We here describe the clinical case of a 28-year-old male with granulocytic sarcoma of the external auditory canal that preceded the relapse of promyelocytic leukaemia.

Danthron, an Anthraquinone Isolated from a Marine Fungus, Is a New Inhibitor of Angiogenesis Exhibiting Interesting Antitumor and Antioxidant Properties.

The role played by a sustained angiogenesis in cancer and other diseases stimulates the interest in the search for new antiangiogenic drugs. In this manuscript, we provide evidence that 1,8- dihydroxy-9,10-anthraquinone (danthron), isolated from the fermentation broth of the marine fungus Chromolaenicola sp. (HL-114-33-R04), is a new inhibitor of angiogenesis. The results obtained with the in vivo CAM assay indicate that danthron is a potent antiangiogenic compound. In vitro studies with human umbilical endothelial cells (HUVEC) reveal that this anthraquinone inhibits certain key functions of activated endothelial cells, including proliferation, proteolytic and invasive capabilities and tube formation. In vitro studies with human breast carcinoma MDA-MB231 and fibrosarcoma HT1080 cell lines suggest a moderate antitumor and antimetastatic activity of this compound. Antioxidant properties of danthron are evidenced by the observation that it reduces the intracellular reactive oxygen species production and increases the amount of intracellular sulfhydryl groups in endothelial and tumor cells. These results support a putative role of danthron as a new antiangiogenic drug with potential application in the treatment and angioprevention of cancer and other angiogenesis-dependent diseases.

Feeding Ecology of the Cuvier's Gazelle (Gazella cuvieri, Ogilby, 1841) in the Sahara Desert.

Knowledge of the feeding ecology of ungulates in arid biomes offers an interesting model for understanding the drought resistance of large desert-adapted herbivores, a crucial issue in the face of increasing desertification due to climate change. To assess the feeding ecology of the endangered Cuvier's gazelle (Gazella cuvieri) in the Sahara desert, we used a multi-method approach combining faecal samples, direct observations, and the recording of indirect signs of feeding. We hypothesised that browser behaviour is the best foraging strategy for species living in hyper-arid environments, mainly due to long periods without grazing opportunities. Complementarily, we explored the effects of the main environmental descriptors (rainfalls and NDVI) on feeding patterns and diet quality. We found that Cuvier's diets are based mainly on acacias (Vachellia tortilis, V. flava) and occasionally on the annual forb Anastatica hierochuntica. In total, eighteen species (five trees, nine shrubs, three herbs, and one grass) belonging to fifteen families were recorded. Our result confirmed the browsers' characteristic of this species, reaffirming its ability to settle in a hostile environment. Acacias stand out as key species consumed at the southernmost limit of their range; hence, future conservation plans and strategies should take this into account for the survival of Cuvier's gazelle in desert environments.

Transfer of bovine embryos into a uterus primed with high progesterone concentrations positively impacts fetal development at 42 days of gestation.

Elevated circulating progesterone (P4) concentrations in the first week after conception have been associated with accelerated post-hatching conceptus elongation. However, the consequences, if any, on the development of the fetus are unknown. The objective of this study was to determine the relationship between early circulating P4 and fetal and placental morphometric characteristics at 42 days of gestation. A previously validated model of asynchronous embryo transfer (ET), known to alter uterine exposure to P4, was used in 107 heifers divided in two replicates (replicate 1: n = 51, replicate 2: n = 56). Heifers were randomly assigned to one of the two following groups: those receiving a Day 7 embryo on Day 7 of the cycle (synchronous; ET_D7, n = 49) and those transferred a Day 7 embryo on Day 9 of the cycle (asynchronous; ET_D9, n = 58). The synchronization protocol was started two days earlier for heifers in the ET_D9 group such that ET was done on the same day for both groups. P4 concentrations were determined from Day 3 after estrus to the day of ET. Pregnant heifers were slaughtered at Day 42 of gestation for fetal and placental morphometric measurements. The effects of the group, replicate, fetal sex, and interactions between these variables on fetal and placental characteristics were determined by ANOVA, while Pearson correlation was employed to assess the linear relationship between P4 concentrations two days before and on the day of ET on the fetal parameters. The uteri of heifers in the ET_D9 group were exposed to higher concentrations (P < 0.0001) of P4 from four days before ET, than heifers in the ET_D7 group. Both group and fetal sex variables impacted on fetal crown-rump length (CRL) (group: P < 0.0001, sex: P = 0.001) and fetal weight (group: P = 0.006, sex: P = 0.003). Fetal sex influenced the amniotic sac area (P = 0.003) and amniotic sac weight (P = 0.004); while the group affected the number of cotyledons (P = 0.0009), and the fetal heart weight (P = 0.018). All these parameters were larger in the ET_D9 group compared with ET_D7, and in males compared with females. There was a positive correlation between P4 concentrations two days before ET and fetal weight and CRL, for each sex or considering all fetuses (R2 ∼0.4, p < 0.05). In conclusion, bovine embryos transferred into a uterus primed with higher P4 concentrations underwent enhanced development reflected in higher weight and size at the beginning of the fetal period.

Genetic profile in patients with complicated acute aortic syndrome: the GEN-AOR study.

INTRODUCTION AND OBJECTIVES: Genetic testing is becoming increasingly important for diagnosis and personalized treatments in aortopathies. Here, we aimed to genetically diagnose a group of acute aortic syndrome (AAS) patients consecutively admitted to an intensive care unit and to explore the clinical usefulness of AAS-associated variants during treatment decision-making and family traceability. METHODS: We applied targeted next-generation sequencing, covering 42 aortic diseases genes in AAS patients with no signs consistent with syndromic conditions. Detected variants were segregated by Sanger sequencing in available family members. Demographic features, risk factors and clinical symptoms were statistically analyzed by Fisher or Fisher-Freeman-Halton Exact tests, to assess their relationship with genetic results. RESULTS: Analysis of next-generation sequencing data in 73 AAS patients led to the detection of 34 heterozygous candidate variants in 14 different genes in 32 patients. Family screening was performed in 31 relatives belonging to 9 families. We found 13 relatives harboring the family variant, of which 10 showed a genotype compatible with the occurrence of AAS. Statistical tests revealed that the factors associated with a positive genetic diagnosis were the absence of hypertension, lower age, family history of AAS and absence of pain. CONCLUSIONS: Our findings broaden the spectrum of the genetic background for AAS. In addition, both index patients and studied relatives benefited from the results obtained, establishing the most appropriate level of surveillance for each group. Finally, this strategy could be reinforced by the use of stastistically significant clinical features as a predictive tool for the hereditary character of AAS. CLINICALTRIALS: gov (Identifier: NCT04751058).

A scale for the identification of the complex chronic pediatric patient (PedCom Scale): A pilot study.

INTRODUCTION AND OBJECTIVES: The complex chronic condition (CCC) is an increasingly prevalent reality in pediatrics. However, having a CCC does not necessarily mean being a complex chronic patient (CCP). From this perspective, we developed an instrument (PedCom Scale) that would facilitate the identification of the CCP. MATERIAL AND METHODS: Initially, general aspects for the classification of patients as CCP were defined. Subsequently, the items of the scale were developed, scoring them from 0.5 to 4 points. We performed a confirmatory factor analysis (CFA) and the internal consistency was studied using alpha-Cronbach. Concordance was evaluated by intra- and inter-observer study. The gold standard was the classification performed by two evaluators after assessing the patient's medical history. The cut-off point for considering the patient as a CCP was established using the ROC curve. RESULTS: The initial version included 43 items with a global content validity index (CVI) of 0.94. A total of 180 patients were included. After the CFA, one item was eliminated, so the final version consists of 42 items with an CVI of 0.95. The alpha-Cronbach value was 0.723. The intraclass correlation coefficient of the test-retest analysis was 0.998 and 0.996 for the inter-observer study. The cut-off point for considering a patient as a CCP was established at 6.5 points, with this results we obtained a sensitivity of 98% and specificity of 94%. CONCLUSIONS: The PedCom Scale is an easy-to-use tool focused on the identification of the CCP. In our sample, it presented satisfactory levels of internal consistency and adequate levels of intra- and inter-observer agreement, with good sensitivity and specificity for the identification of the CCP.

Paraneoplastic autoimmune autonomic ganglionopathy as the first symptom of bladder cancer: a case report and review of literature.

BACKGROUND: Autoimmune autonomic ganglionopathy is a rare, immune-mediated disorder associated with anti-ganglionic α3-subunit nicotinic acetylcholine receptor (anti-α3gAChR) antibodies, which bind to acetylcholine receptor in autonomic ganglia (parasympathetic and sympathetic) leading to autonomic failure. This disorder is mostly associated with viral infections, but it can also be associated with systemic malignancies. Here, we report the case of a paraneoplastic autonomic ganglionopathy as the first symptom of bladder cancer. METHOD: Case report. RESULTS: A 47-year-old man, without medical history of interest, stated to the emergency department for progressive blurry vision with eye and mouth dryness, constipation, and dizziness upon standing for the last 2 weeks. Orthostatic hypotension was demonstrated by a drop in 13.3 mmHg mean blood pressure (BP) from supine (100/60 mmHg) to 45° reclining sitting position (80/50 mmHg). Blood tests, chest X-ray, brain MRI, and electroneuronography were unremarkable. Electrochemical skin conductance was reduced. Serological examination was positive for anti-α3gAChR antibodies. A full-body CT scan revealed a bladder tumor, which was treated by transurethral bladder resection. The pathologic study demonstrated a low-grade non-muscle-invasive bladder urothelial carcinoma. After tumor resection, and treatment with intravenous immunoglobulins and corticoids, a gradually improvement was observed. Today, the patient remains asymptomatic. CONCLUSION: Subacute panautonomic failure can be the first symptom for systemic malignancies. This case reports a paraneoplastic autonomic ganglionopathy as the first symptom of bladder cancer. This case highlights the importance of a systemic study to rule out the presence of cancer when autoimmune autonomic ganglionopathy is present.

Comparing infant and toddler sleep patterns prior to and during the first wave of home confinement due to COVID-19 in Spain.

Recent literature has shown that sleep patterns are shaped during the first years of life, playing a relevant role in children's functioning. We focused on comparing sleep patterns in infants and toddlers in Spain before and during COVID-19 home confinement to assess the immediate impact on sleep patterns. We compared data from two cross-sectional surveys from parents of 1658 children three to 36 months of age from Spain. One conducted before COVID-19 (2017-2018, n = 1380) and another during COVID-19 pandemic (March-May of 2020, n = 254). We used an internet self-administrated questionnaire using the Brief Infant Sleep Questionnaire (BISQ) criteria in both surveys. During confinement, infants and toddlers went to sleep later (median bedtime 21:30 before confinement vs. 21:36 during confinement (p = 0.004)). More infants and toddlers showed longer sleep latencies (> 30 min) during confinement median 33.9% versus 12.3% (p < 0.001). Based on the recommended BISQ criteria, we observed an increase in poor sleepers meeting at least one criterion of inadequate patterns during confinement (p < 0.001). Parental perception of a child's sleep as problematics were 39.4% and 44.1% (adjusted p = 0.363) before and under lockdown, respectively. CONCLUSION: Home confinement generally affected infant's and toddler's sleep patterns negatively; however, parents did not report worse perception of sleep quality of their children. Follow-up studies can help understand the potential long-term effects of the COVID-19 pandemic on sleep patterns. WHAT IS KNOWN: • Adequate sleep patterns in infants and toddlers are relevant as they are linked to proper and long-term social-emotional development as well as adequate daytime functioning. • Regarding sleep patterns in paediatrics during the COVID pandemic, recent literature has described an increase in total daily sleep time as well as more exposure to screens in children and adolescents, providing evidence of immediate collateral consequences of the COVID-19 outbreak. WHAT IS NEW: • Comparing sleep patterns in two samples of infants and toddlers in Spain before and during COVID-confinement, we found later bedtimes as well as a significant increase in infants' and toddlers' sleep latency by >30 min during confinement. • Parental self-reported questionnaire during COVID-19 home confinement reported an overall worsening of their children's sleep based on the BISQ criteria.

Platelet rich plasma and plasma rich in growth factors for split-thickness skin graft donor site treatment in the burn patient setting: A randomized clinical trial.

INTRODUCTION: Management of donor site morbidity in the setting of split thickness skin graft (STSG) is of crucial importance with no superior wound dressing described to date and the growing need of decreasing epithelializing time. The purpose of the study was to compare the standard of care using a hydrocolloid dressing to platelet rich plasma (PRP) and plasma rich in growth factors (PRGF) in order to determine its therapeutic potential in this setting. METHODS: A randomized clinical trial was conducted in which each patient served as its own control. PRGF was obtained by means of freeze-thaw out of the PRP from the subject of the study. Patients from the study had three donor sites and each donor site received either to PRP, PRGF or the standard of care, hydrocolloid. The main variable was time to epithelialization, and secondary variables subject to study were pain, quality of the scar, complications and cost. RESULTS: 20 patients were recruited with a total number of 60 donor sites to study. On the 8th post-operative day 55% and 45% of the sites treated with PRP and PRGF, respectively, complete epithelialization was observed as compared to 20% of the sites treated with hydrocolloid, statistical significance was achieved between the latter two (p = 0.036). The areas treated with PRP and PRGF received inferior values on the visual analog scale on post-op day 5 and 8 compared to hydrocolloid. Values on wound healing metrics were lower in the PRP when compared to hydrocolloid. No adverse effects were recorded. CONCLUSION: Donor site of STSG treated with PRP in the setting of the burn patient decreased time to epithelialization. In our study a better pain control and in scar quality was observed in both, the PRP and PRGF group.