The burden of rare variants in DPYS gene is a novel predictor of the risk of developing severe fluoropyrimidine-related toxicity.

BACKGROUND: Despite a growing number of publications highlighting the potential impact on the therapy outcome, rare genetic variants (minor allele frequency < 1%) in genes associated to drug adsorption, distribution, metabolism, and elimination are poorly studied. Previously, rare germline DPYD missense variants were shown to identify a subset of fluoropyrimidine-treated patients at high risk for severe toxicity. Here, we investigate the impact of rare genetic variants in a panel of 54 other fluoropyrimidine-related genes on the risk of severe toxicity. METHODS: The coding sequence and untranslated regions of 54 genes related to fluoropyrimidine pharmacokinetics/pharmacodynamics were analyzed by next-generation sequencing in 120 patients developing grade 3-5 toxicity (NCI-CTC vs3.0) and 104 matched controls. Sequence Kernel Association Test (SKAT) analysis was used to select genes with a burden of genetic variants significantly associated with risk of severe toxicity. The statistical association of common and rare genetic variants in selected genes was further investigated. The functional impact of genetic variants was assessed using two different in silico prediction tools (Predict2SNP; ADME Prediction Framework). RESULTS: SKAT analysis highlighted DPYS and PPARD as genes with a genetic mutational burden significantly associated with risk of severe fluoropyrimidine-related toxicity (Bonferroni adjusted P = 0.024 and P = 0.039, respectively). Looking more closely at allele frequency, the burden of rare DPYS variants was significantly higher in patients with toxicity compared with controls (P = 0.047, Mann-Whitney test). Carrying at least one rare DPYS variant was associated with an approximately fourfold higher risk of severe cumulative (OR = 4.08, P = 0.030) and acute (OR = 4.21, P = 0.082) toxicity. The burden of PPARD rare genetic variants was not significantly related to toxicity. Some common variants with predictive value in DPYS and PPARD were also identified: DPYS rs143004875-T and PPARD rs2016520-T variants predicted an increased risk of severe cumulative (P = 0.002 and P = 0.001, respectively) and acute (P = 0.005 and P = 0.0001, respectively) toxicity. CONCLUSION: This work demonstrated that the rare mutational burden of DPYS, a gene strictly cooperating with DPYD in the catabolic pathway of fluoropyrimidines, is a promising pharmacogenetic marker for precision dosing of fluoropyrimidines. Additionally, some common genetic polymorphisms in DPYS and PPARD were identified as promising predictive markers that warrant further investigation.

Shared and distinct abnormalities in sleep-wake patterns and their relationship with the negative symptoms of Schizophrenia Spectrum Disorder patients.

Sleep and rest-activity-rhythm (RAR) abnormalities are commonly reported in schizophrenia spectrum disorder (SSD) patients. However, an in-depth characterization of sleep/RAR alterations in SSD, including patients in different treatment settings, and the relationship between these alterations and SSD clinical features (e.g., negative symptoms) is lacking. SSD (N = 137 altogether, N = 79 residential and N = 58 outpatients) and healthy control (HC) subjects (N = 113) were recruited for the DiAPAson project. Participants wore an ActiGraph for seven consecutive days to monitor habitual sleep-RAR patterns. Sleep/rest duration, activity (i.e., M10, calculated on the 10 most active hours), rhythm fragmentation within days (i.e., intra-daily variability, IV; beta, steepness of rest-active changes), and rhythm regularity across days (i.e., inter-daily stability, IS) were computed in each study participant. Negative symptoms were assessed in SSD patients with the Brief Negative Symptom Scale (BNSS). Both SSD groups showed lower M10 and longer sleep/rest duration vs. HC, while only residential patients had more fragmented and irregular rhythms than HC. Compared to outpatients, residential patients had lower M10 and higher beta, IV and IS. Furthermore, residential patients had worse BNSS scores relative to outpatients, and higher IS contributed to between-group differences in BNSS score severity. Altogether, residentials and outpatients SSD had both shared and unique abnormalities in Sleep/RAR measures vs. HC and relative to one another, which also contributed to the patients' negative symptom severity. Future work will help establish whether improving some of these measures may ameliorate the quality of life and clinical symptoms of SSD patients.

Xanthan-based chlorhexidine gel effects in non-surgical periodontal therapy? A meta-analysis.

OBJECTIVE: To carry out a systematic review and meta-analysis of randomized controlled clinical trials (RCTs) and controlled clinical trials (CCTs) comparing scaling and root planing (SRP) or placebo with subgingival application of xanthan-based CHX (chlorhexidine) gel as adjunct to SRP. MATERIALS AND METHODS: The literature search was carried out in PubMed/MEDLINE, EMBASE, and SCOPUS; primary outcomes were probing pocket depth (PPD) reduction and gain in clinical attachment level (CAL). RESULTS: Overall, 15 studies were included. Three studies were judged to be at moderate risk of bias while the remaining 12 were rated at high risk of bias. A significant improvement in PPD reduction (standardized mean difference, SMD, 0.87, 95% CI, 0.41-1.34) and CAL gain (SMD = 0.84, 95% CI, 0.36-1.33) emerged for the SRP + CXH gel compared to the SRP alone group, in the presence of significant high heterogeneity among the studies. CONCLUSIONS: Our systematic review and meta-analysis showed that xanthan-based chlorhexidine gel as adjunct to non-surgical periodontal therapy gives benefit in terms of PPD reduction and CAL gain as compared to non-surgical periodontal therapy only. Since there was high heterogeneity among studies and the quality of the evidence is low, further studies characterized by a better methodology, adequate sample size and longer follow-up are warranted in the next future. REGISTRATION: The protocol of this scoping review was registered in the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/PROSPERO) with ID: CRD42023391589.

FGF-trapping hampers cancer stem-like cells in uveal melanoma.

BACKGROUND: Cancer stem-like cells (CSCs) are a subpopulation of tumor cells responsible for tumor initiation, metastasis, chemoresistance, and relapse. Recently, CSCs have been identified in Uveal Melanoma (UM), which represents the most common primary tumor of the eye. UM is highly resistant to systemic chemotherapy and effective therapies aimed at improving overall survival of patients are eagerly required. METHODS: Herein, taking advantage from a pan Fibroblast Growth Factor (FGF)-trap molecule, we singled out and analyzed a UM-CSC subset with marked stem-like properties. A hierarchical clustering of gene expression data publicly available on The Cancer Genome Atlas (TCGA) was performed to identify patients' clusters. RESULTS: By disrupting the FGF/FGF receptor (FGFR)-mediated signaling, we unmasked an FGF-sensitive UM population characterized by increased expression of numerous stemness-related transcription factors, enhanced aldehyde dehydrogenase (ALDH) activity, and tumor-sphere formation capacity. Moreover, FGF inhibition deeply affected UM-CSC survival in vivo in a chorioallantoic membrane (CAM) tumor graft assay, resulting in the reduction of tumor growth. At clinical level, hierarchical clustering of TCGA gene expression data revealed a strong correlation between FGFs/FGFRs and stemness-related genes, allowing the identification of three distinct clusters characterized by different clinical outcomes. CONCLUSIONS: Our findings support the evidence that the FGF/FGFR axis represents a master regulator of cancer stemness in primary UM tumors and point to anti-FGF treatments as a novel therapeutic strategy to hit the CSC component in UM.

Does the rapid initiation of antiretroviral therapy at HIV diagnosis impact virological response in a real-life setting? A single-centre experience in Northern Italy.

Rapid initiation of antiretroviral therapy (ART) has been proven efficacious and safe, but more investigations are needed to define feasibility of rapid ART approach in real-life settings.We conducted a retrospective, observational study on newly HIVdiagnosed patients referred to our Infectious Diseases Department from September 1st, 2015, to July 31st, 2019. According to the timing of ART initiation, we distinguished 3 groups of patients (rapid, intermediate and late group) and represented the trend of virological response during a 400-days-period. The hazard ratios of each predictor on viral suppression were estimated through the Cox proportional hazard model.The median time from HIV diagnosis to the first medical referral was 15 days and the median time from the first care access to therapy start was 24 days. Among patients, 37.6% started ART within 7 days, 20.6% between 8 and 30 days, and 41.8% after 30 days. Longer time to ART start and higher baseline viral load were associated with a lower probability of viral suppression. After one year, all groups showed a high viral suppression rate (99%). In a high-income setting the rapid ART approach seems useful to accelerate viral suppression which is great over time regardless of ART initiation timing.

Academic skills in children with cerebral palsy and specific learning disorders.

AIM: To investigate the prevalence and clinical manifestations of reading, writing, and mathematics disorders in children with cerebral palsy (CP). We explored how the clinical profile of these children differed from those with specific learning disorders (SLDs), taking into account several factors, particularly IQ scores, neuropsychological aspects, and the presence of a visual impairment. METHOD: A prospective cross-sectional study was conducted in 42 children with CP (mean age 9 years 8 months; SD = 2 years 2 months) and 60 children with SLDs (mean age 10 years; SD = 1 year 7 months). Clinical characteristics, neuromotor and cognitive profiles, neuropsychological aspects (speech performance, academic skills, visual attention, phonological awareness, working memory), and signs of visual impairment (visual acuity, contrast sensitivity, visual field, oculomotor functions) were assessed. A machine learning approach consisting of a random forest algorithm, where the outcome was the diagnosis and the covariates were the clinical variables collected in the sample, was used for the analyses. RESULTS: About 59% of the children with CP had reading, writing, or mathematics disorders. Children with CP with learning disorders had a low performance IQ, normal phonological awareness, and working memory difficulties, whereas children with SLDs had normal performance IQ, impaired phonological awareness, and mild working memory difficulties. There were no differences in verbal IQ between the two groups. INTERPRETATION: Learning disorders are frequently associated with CP, with different clinical characteristics, compared with SLDs. Assessment of academic skills is mandatory in these children, even if the IQ is normal. At school age, specific interventions to promote academic skills in children with CP could be a major rehabilitative goal.

Development and Rasch Validation of an Observational Assessment Tool of Upper Limb Functional Impairment in Stroke Survivors: Functional Assessment Test for Upper Limb.

OBJECTIVE: To develop and validate a quick observational clinical tool, the Functional ASsessment Test for Upper Limb (FAST-UL), for the evaluation of upper limb impairment in goal-directed functional-oriented motor tasks after stroke. DESIGN: Observational, cross-sectional, psychometric study. SETTING: Inpatient and outpatient rehabilitation clinic. PARTICIPANTS: A total of 188 post-stroke survivors (mean age 65.2±17.7 years, 61% men, 48% with ischemic stroke and 66% in the sub-acute phase; N=188). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Principal component analysis and Rasch analysis through a Partial Credit Model were used to assess the structure and psychometric properties of the 5 items of the FAST-UL (Hand to Mouth [HtM], Reach to Target, Prono-Supination, Grasp and Release, and Pinch and Release [PaR]). RESULTS: The Cronbach's α equal to 0.96 was indicative of an acceptable internal consistency; the reliability, as measured through the Person Separation Reliability equal to 0.87, was good. The FAST-UL tool was unidimensional. All the FAST-UL items were found to fit well the Rasch measurement model. The easiest to perform FAST-UL item was the HtM movement while the most difficult was the PaR movement. CONCLUSIONS: The FAST-UL is a quick, easy-to-administer observational assessment tool of upper limb motor impairment in post-stroke survivors with good item-level psychometric properties.

L1CAM expression as a predictor of platinum response in high-risk endometrial carcinoma.

For high-risk endometrial cancer (EC) patients, adjuvant chemotherapy is recommended to improve outcome. Yet, predictive biomarkers for response to platinum-based chemotherapy (Pt-aCT) are currently lacking. We tested expression of L1 cell-adhesion molecule (L1CAM), a well-recognised marker of poor prognosis in EC, in tumour samples from high-risk EC patients, to explore its role as a predictive marker of Pt-aCT response. L1CAM expression was determined using RT-qPCR and immunohistochemistry in a cohort of high-risk EC patients treated with Pt-aCT and validated in a multicentric independent cohort. The association between L1CAM and clinicopathologic features and L1CAM additive value in predicting platinum response were determined. The effect of L1CAM gene silencing on response to carboplatin was functionally tested on primary L1CAM-expressing cells. Increased L1CAM expression at both genetic and protein level correlated with high-grade, non-endometrioid histology and poor response to platinum treatment. A predictive model adding L1CAM to prognostic clinical variables significantly improved platinum response prediction (C-index 78.1%, P = .012). In multivariate survival analysis, L1CAM expression was significantly associated with poor outcome (HR: 2.03, P = .019), potentially through an indirect effect, mediated by its influence on response to chemotherapy. In vitro, inhibition of L1CAM significantly increased cell sensitivity to carboplatin, supporting a mechanistic link between L1CAM expression and response to platinum in EC cells. In conclusion, we have demonstrated the role of L1CAM in the prediction of response to Pt-aCT in two independent cohorts of high-risk EC patients. L1CAM is a promising candidate biomarker to optimise decision making in high-risk patients who are eligible for Pt-aCT.

Physical, cognitive and mental health outcomes in 1-year survivors of COVID-19-associated ARDS.

We report on the outcome of 114 COVID-19-associated acute respiratory distress syndrome (ARDS) survivors evaluated at 3, 6 and 12 months after intensive care unit discharge with assessment of physical, mental and cognitive impairments. Critical illness polyneuromyopathy was diagnosed in 23 patients (39%). Handgrip dynamometry was 70% predicted at 3 months and significantly improved over time, whereas the 6 min walk test (80% predicted) and severe fatigue (27% of patients) did not. Independence in activities of daily living (ADL) was achieved by 98% at 3 months. Cognitive impairment (28% at 3 months) improved over time, whereas depression, anxiety and post-traumatic stress disorder symptoms, present in 9%, 10% and 4% at 3 months, did not. Normalised health-related quality of life was good. COVID-19-associated ARDS leads to persisting impairment in performance-based measures of physical function, while ADL, cognitive and mental health status, and health-related quality of life may be less impaired. Trial registration number NCT04608994.

Psychological and Emotional Impact of COVID-19 Pandemic on People Living with Chronic Disease: HIV and Cancer.

People living with chronic disease (PLWCD) are the frailest category, both for the risk of severe COVID-19 illness and for the impact on the care continuum. Aim of this study was to analyze coping strategies and resilience in people living with HIV (PLWH) compared to people living with oncological diseases (PLWOD) during COVID-19 pandemic. We administrated an anonymous questionnaire, which explored the emotional experience, the demographic factors linked to a COVID-19-related stress syndrome, the patient's perception about the adequacy of clinical undertaking from the hospital and the resilience. We analyzed 324 questionnaires. There were no significant differences in prevalence of psychological distress among the whole cohort; however, PLWOD were calmer, less troubled, and more serene than PLWH. Moreover, PLWH smoked more, ate more, and gained more weight than PLWOD. Most patients didn't feel lonely and continued to take pleasure from their activities. No differences in resilience were found between the groups. In the whole cohort lower levels of resilience were found in patients that were unemployed, with history of psychological disorders and in those who experienced more feelings of anger, anxiety and concern. In our study, patients seemed to preserve their well-being, and to activate adaptive coping during the pandemic.

Transcranial Doppler as a screening test to exclude intracranial hypertension in brain-injured patients: the IMPRESSIT-2 prospective multicenter international study.

BACKGROUND: Alternative noninvasive methods capable of excluding intracranial hypertension through use of transcranial Doppler (ICPtcd) in situations where invasive methods cannot be used or are not available would be useful during the management of acutely brain-injured patients. The objective of this study was to determine whether ICPtcd can be considered a reliable screening test compared to the reference standard method, invasive ICP monitoring (ICPi), in excluding the presence of intracranial hypertension. METHODS: This was a prospective, international, multicenter, unblinded, diagnostic accuracy study comparing the index test (ICPtcd) with a reference standard (ICPi), defined as the best available method for establishing the presence or absence of the condition of interest (i.e., intracranial hypertension). Acute brain-injured patients pertaining to one of four categories: traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) or ischemic stroke (IS) requiring ICPi monitoring, were enrolled in 16 international intensive care units. ICPi measurements (reference test) were compared to simultaneous ICPtcd measurements (index test) at three different timepoints: before, immediately after and 2 to 3 h following ICPi catheter insertion. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated at three different ICPi thresholds (> 20, > 22 and > 25 mmHg) to assess ICPtcd as a bedside real-practice screening method. A receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC) was used to evaluate the discriminative accuracy and predictive capability of ICPtcd. RESULTS: Two hundred and sixty-two patients were recruited for final analysis. Intracranial hypertension (> 22 mmHg) occurred in 87 patients (33.2%). The total number of paired comparisons between ICPtcd and ICPi was 687. The NPV was elevated (ICP > 20 mmHg = 91.3%, > 22 mmHg = 95.6%, > 25 mmHg = 98.6%), indicating high discriminant accuracy of ICPtcd in excluding intracranial hypertension. Concordance correlation between ICPtcd and ICPi was 33.3% (95% CI 25.6-40.5%), and Bland-Altman showed a mean bias of -3.3 mmHg. The optimal ICPtcd threshold for ruling out intracranial hypertension was 20.5 mmHg, corresponding to a sensitivity of 70% (95% CI 40.7-92.6%) and a specificity of 72% (95% CI 51.9-94.0%) with an AUC of 76% (95% CI 65.6-85.5%). CONCLUSIONS AND RELEVANCE: ICPtcd has a high NPV in ruling out intracranial hypertension and may be useful to clinicians in situations where invasive methods cannot be used or not available. TRIAL REGISTRATION: NCT02322970 .

Aneurismal subarachnoid hemorrhage during the COVID-19 outbreak in a Hub and Spoke system: observational multicenter cohort study in Lombardy, Italy.

BACKGROUND: Lombardy was the most affected Italian region by the first phase of the COVID-19 pandemic and underwent urgent reorganization for the management of emergencies, including subarachnoid hemorrhage from a ruptured cerebral aneurysm (aSAH). The aim of the study was to define demographics, clinical, and therapeutic features of aSAH during the COVID-19 outbreak and compare these with a historical cohort. METHODS: In this observational multicenter cohort study, patients aged 18 years or older, who were diagnosed with aSAH at the participating centers in Lombardy from March 9 to May 10, 2020, were included (COVID-19 group). In order to minimize bias related to possible SAH seasonality, the control group was composed of patients diagnosed with aSAH from March 9 to May 10 of the three previous years, 2017-2018-2019 (pre-pandemic group). Twenty-three demographic, clinical, and therapeutic features were collected. Statistical analysis was performed. RESULTS: Seventy-two patients during the COVID-19 period and 179 in the control group were enrolled at 14 centers. Only 4 patients were positive for SARS-CoV-2. The "diagnostic delay" was significantly increased (+ 68%) in the COVID-19 group vs. pre-pandemic (1.06 vs. 0.63 days, respectively, p-value = 0.030), while "therapeutic delay" did not differ significantly between the two periods (0.89 vs. 0.74 days, p-value = 0.183). Patients with poor outcome (GOS at discharge from 1 to 3) were higher during the COVID-19 period (54.2%) compared to pre-pandemic (40.2%, p = 0.044). In logistic regression analysis, in which outcome was the dichotomized Glasgow Outcome Scale (GOS), five variables showed p-values < 0.05: age at admission, WFNS grade, treatment (none), days in ICU, and ischemia. CONCLUSIONS: We documented a significantly increased "diagnostic delay" for subarachnoid hemorrhages during the first COVID-19 outbreak in Lombardy. However, despite the dramatic situation that the healthcare system was experiencing, the Lombardy regional reorganization model, which allowed centralization of neurosurgical emergencies such as SAHs, avoided a "therapeutic delay" and led to results overall comparable to the control period.

ß-Galactosylceramidase Deficiency Causes Upregulation of Long Pentraxin-3 in the Central Nervous System of Krabbe Patients and Twitcher Mice.

Globoid cell leukodystrophy (GLD), or Krabbe disease, is a neurodegenerative sphingolipidosis caused by genetic deficiency of lysosomal ß-galactosylceramidase (GALC), characterized by neuroinflammation and demyelination of the central (CNS) and peripheral nervous system. The acute phase protein long pentraxin-3 (PTX3) is a soluble pattern recognition receptor and a regulator of innate immunity. Growing evidence points to the involvement of PTX3 in neurodegeneration. However, the expression and role of PTX3 in the neurodegenerative/neuroinflammatory processes that characterize GLD remain unexplored. Here, immunohistochemical analysis of brain samples from Krabbe patients showed that macrophages and globoid cells are intensely immunoreactive for PTX3. Accordingly, Ptx3 expression increases throughout the course of the disease in the cerebrum, cerebellum, and spinal cord of GALC-deficient twitcher (Galctwi/twi) mice, an authentic animal model of GLD. This was paralleled by the upregulation of proinflammatory genes and M1-polarized macrophage/microglia markers and of the levels of PTX3 protein in CNS and plasma of twitcher animals. Crossing of Galctwi/twi mice with transgenic PTX3 overexpressing animals (hPTX3 mice) demonstrated that constitutive PTX3 overexpression reduced the severity of clinical signs and the upregulation of proinflammatory genes in the spinal cord of P35 hPTX3/Galctwi/twi mice when compared to Galctwi/twi littermates, leading to a limited increase of their life span. However, this occurred in the absence of a significant impact on the histopathological findings and on the accumulation of the neurotoxic metabolite psychosine when evaluated at this late time point of the disease. In conclusion, our results provide the first evidence that PTX3 is produced in the CNS of GALC-deficient Krabbe patients and twitcher mice. PTX3 may exert a protective role by reducing the neuroinflammatory response that occurs in the spinal cord of GALC-deficient animals.

Clinical evaluation of air polishing with erythritol powder followed by ultrasonic calculus removal versus conventional ultrasonic debridement and rubber cup polishing for the treatment of gingivitis: A split-mouth randomized controlled clinical trial.

OBJECTIVES: To evaluate the clinical efficacy in the short-term resolution of gingivitis of a novel protocol involving full-mouth erythritol powder air polishing followed by ultrasonic calculus removal. METHODS: Forty-one healthy patients completed the study. Following a split-mouth design, quadrants 1-4 and 2-3 were randomly allocated to receive air polishing followed by ultrasonic calculus removal (A+US) or traditional full-mouth ultrasonic debridement followed by polishing with a rubber cup and prophylactic paste (US+P). Bleeding on probing (BoP) and plaque index (PI) were collected at baseline and 2 and 4 weeks. Moreover, the residual plaque area (RPA), treatment time and patient comfort/satisfaction were evaluated at the end of the treatment. RESULTS: Both treatments showed a significant reduction in BoP and PI. At 4 weeks, A+US seems to reach a statistically significant lower BoP (8.7% [6.9; 10.9] vs. 11.6%[9.3; 14.4], p < 0.0001) and PI (10.7% [8.9; 13.0] vs. 12.3% [10.2; 14.9], p = 0.033). Moreover, A+US treatment time lasted on average 9.2% less than US+P (p < 0.0001) and was the preferred treatment for a significantly higher number of patients (73.2% vs. 17.1%, p = 0.0001). CONCLUSION: The A+US protocol is suitable for the short-term resolution of plaque-induced gingivitis.

Descriptive modification of inflammatory markers in HIV patients after cART initiation according to gender, smoking habit, CMV infection, BMI and serum lipids.

Persistent inflammation, despite anti-retroviral therapy (ART), is an independent predictor of mortality and comorbidities in HIV infection. Multiple factors, including lifestyle and chronic viral coinfections, may contribute. Several of these factors are also associated with a chronic inflammation in the general population. Little is known about the degree to which these factors influence inflammation in HIV infection, particularly within the first year of ART. The purpose of this study was to distinguish the effects of factors (gender, body mass index, cholesterol and triglyceride levels, smoke habit and cytomegalovirus seropositivity), known to contribute to inflammation, on inflammation biomarkers over the first year of ART in HIV-infected patients. Linear mixed model analysis revealed significant biomarker decreases [soluble CD14 (s-CD14), soluble CD163 (s-CD163) and D-dimer (DD)], or increases [C Reactive Protein (CRP) and interleukin-6 (IL-6)] over time in the whole cohort, differences in most categories (genders for IL-6, smoke habit for s-CD14, cytomegalovirus infection for s-CD163 and IL-6) and in some category × time interactions [gender for interleukin-7 (IL-7)], cytomegalovirus infection for s-CD14 and cholesterol levels for s-CD14 and Tumor Necrosis Factor α (TNF-α)]. This explorative longitudinal study suggests further investigations on targeting inflammation pathophysiology in HIV-infected patients on ART.

Multidimensional Prognostic Index (MPI) score has the major impact on outcome prediction in elderly surgical patients with colorectal cancer: The FRAGIS study.

BACKGROUND: This study aims (I) to evaluate whether the Multidimensional Prognostic Index (MPI) score is associated with postoperative outcomes and (II) to develop a prognostic model for individual complication-risk prediction following colorectal cancer (CRC) surgery. METHOD: This is a prospective multicentric cohort study. Consecutive ≥75-year-old candidates for elective CRC surgery were enrolled from October 2017 to August 2019. Patients underwent standardized preoperative geriatric assessment including the MPI. Patients with MPI score > 0.33 were classified as frail. Logistic regression models were employed to evaluate variables associated with major postoperative complications and mortality, using 10-fold cross-validated LASSO (least absolute shrinkage and selection operator) for model selection. RESULTS: In all, 104 patients were included, 34 (33%) had MPI score > 0.33. Major postoperative complications occurred in 52% of frail versus 16% of fit (MPI score ≤ 0.33) patients (p < .01). Both 30-day (9% vs. 0%; p = .033) and 90-day mortality (18% vs. 1%; p < .01) were higher among frail patients. In multivariate analysis, MPI score was associated with adverse outcomes. A final postoperative complication predictive model was created, including MPI score, gait-speed test, ASA (American Society of Anesthesiology) score, surgical approach, and stoma creation. CONCLUSION: MPI score is strongly associated with postoperative major complications in CRC elderly patients and it is a primary component of an individual prediction model.

Early visual training and environmental adaptation for infants with visual impairment.

AIM: To evaluate the effectiveness of early visual training and environmental adaptation on visual function and neurological development in infants with visual impairment. METHOD: This was a pilot intervention clinical trial study. Thirty infants (mean age 5.9mo, SD 2.1mo, range 4-11mo; 16 males, 14 females) with peripheral visual impairment (PVI, n=15) or cerebral visual impairment (CVI, n=15) participated in a 6-month visual intervention programme. Thirty matched infants (mean age 6mo, SD 1.4mo, range 4-9mo; 18 males, 12 females) served as a comparison group. Primary outcome measures were visual acuity, contrast sensitivity, and qualitative ocular motor functions. Secondary outcomes were scores on the Griffiths Mental Developmental Scales (GMDS). RESULTS: The treatment group showed a significant improvement in all the primary outcomes (p<0.01). The comparison group improved only in visual acuity and contrast sensitivity (p<0.01). The treatment group showed greater improvement than the comparison group in visual fixation (p=0.033) and smooth pursuit (p<0.01). The CVI subgroup showed greater improvement in visual acuity than the PVI subgroup (p<0.01). GMDS subscales of hand-eye coordination (p=0.01) and performance (p<0.01) increased in the treatment group, while the total score of the comparison group decreased, driven by language (p=0.039) and hand-eye coordination (p=0.025) subscales. INTERPRETATION: Results suggest that, in infants with visual impairment, visual function and certain developmental outcomes improve in response to early visual training and environmental adaptation, in an interactive context. What this paper adds Early visual training and environmental adaptation are associated with enhanced visual acuity and smooth pursuit. Early visual training and environmental adaptation are associated with an improvement of neurological developmental outcome. Performance, hand-eye coordination, and language scores in Griffiths Mental Developmental Scales increase after visual training. After training, visual acuity improves more in infants with cerebral rather than anterior visual impairment. Type and complexity of visual impairment contribute to determine infants' response to training.

COVID-19 incidence and mortality in Lombardy, Italy: An ecological study on the role of air pollution, meteorological factors, demographic and socioeconomic variables.

Lombardy, the most populated and industrialized Italian region, was the epicentre of the first wave (March and April 2020) of COVID-19 in Italy and it is among the most air polluted areas of Europe. We carried out an ecological study to assess the association between long-term exposure to particulate matter (PM) and nitrogen dioxide (NO2) on COVID-19 incidence and all-cause mortality after accounting for demographic, socioeconomic and meteorological variables. The study was based on publicly available data. Multivariable negative binomial mixed regression models were fitted, and results were reported in terms of incidence rate ratios (IRRs) and standardized mortality ratios (SMR). The effect of winter temperature and humidity was modelled through restricted cubic spline. Data from 1439 municipalities out of 1507 (95%) were included in the analyses, leading to a total of 61,377 COVID-19 cases and 40,401 deaths from all-causes collected from February 20th to April 16th and from March 1st to April 30th, 2020, respectively. Several demographic and socioeconomic variables resulted significantly associated with COVID-19 incidence and all-cause mortality in a multivariable fashion. An increase in average winter temperature was associated with a nonlinear decrease in COVID-19 incidence and all-cause mortality, while an opposite trend emerged for the absolute humidity. An increase of 10 µg/m3 in the mean annual concentrations of PM2.5 and PM10 over the previous years was associated with a 58% and 34% increase in COVID-19 incidence rate, respectively. Similarly, a 10 µg/m3 increase of annual mean PM2.5 concentration was associated with a 23% increase in all-cause mortality. An inverse association was found between NO2 levels and COVID-19 incidence and all-cause mortality. Our ecological study showed that exposure to PM was significantly associated with the COVID-19 incidence and excess mortality during the first wave of the outbreak in Lombardy, Italy.

Efficacy of the additional use of subgingival air polishing with erythritol powder in the treatment of periodontitis patients: a randomized controlled clinical trial.

OBJECTIVES: To date, scarce evidence exists around the application of subgingival air polishing during treatment of severe periodontitis. The aim of this study was to evaluate the benefits of subgingival air polishing during non-surgical treatment of deep bleeding pockets in stages III-IV periodontitis patients MATERIALS AND METHODS: Forty patients with stages III-IV periodontitis were selected, and pockets with probing depth (PD) 5-9 mm and bleeding on probing (BoP) were selected as experimental sites. All patients underwent a full-mouth session of erythritol powder supragingival air polishing and ultrasonic instrumentation. Test group received additional subgingival air polishing at experimental sites. The proportion of experimental sites shifting to PD ≤ 4 mm and no BoP at 3 months (i.e., non-bleeding closed pockets, NBCPs) was regarded as the primary outcome variable. RESULTS: The proportion of NBCP was comparable between test and control group (47.9 and 44.7%, respectively). Baseline PD of 7-9 mm, multi-rooted teeth and the presence of plaque negatively influenced the probability of obtaining NBCP. CONCLUSIONS: The additional application of subgingival air polishing does not seem to provide any significant clinical advantage in achieving closure at moderate to deep bleeding pockets in treatment of stages III-IV periodontitis patients. The study was registered on Clinical Trials.gov (NCT04264624). CLINICAL RELEVANCE: While air polishing can play a role in biofilm removal at supragingival and shallow sites, ultrasonic root surface debridement alone is still the choice for initial treatment of deep bleeding periodontal pockets.

Efficacy of sonic versus manual toothbrushing after professional mechanical plaque removal: A 6-month randomized clinical trial.

AIM: The aim of this study was to compare the efficacy of two brushing methods (manual vs. sonic) in terms of plaque control after a session of professional mechanical plaque removal (PMPR). METHODS: Subjects with gingivitis underwent a session of PMPR and were randomly assigned to sonic (SB) or manual brushing (MB). Oral hygiene instructions were provided at baseline (BL), 2 (T0a), 4 (T0b) and 6 weeks (T1) and 6 months (T2). Plaque Index (PI), Gingival Index (GI) and bleeding on probing (BoP) were measured at BL, T1 and T2. The proportion of sites with PI, GI and BoP was modelled at site level using a negative binomial regression fitted via generalized linear mixed model accounting for intra-patient correlation. RESULTS: Thirty-two subjects were selected, 16 assigned to each group and 31 completed the study. PI, BoP and GI were comparable at BL. At T1, PI was successfully maintained at 6.21% for SB and 22.81% for MB, while at T2 reached 11.34% for SB and 28% for MB, favouring the SB group (p < 0.001). GI and BoP were significantly lower in the SB group at T1, with a BoP reduction for SB about 3 times higher than MB (p < 0.001). These parameters then levelled at T2 between the groups, with BOP reaching 0.14% versus 0.05% (p = 0.356) and GI 1.75% versus 3.52% (p = 0.020). CONCLUSION: Sonic brushing seemed to maintain a lower PI score compared to a manual brush at 6 months. BoP and GI resulted comparable.