Zygomatic implant guided rehabilitation based on inverted support technique: a pilot study.

OBJECTIVE: Zygomatic implant insertion surgery is a challenging operation. The primary aim of this pilot study was to assess the accuracy of EZgoma® "Inverted Support Technique" for the zygomatic implant-guided surgery. Secondly, any factors which may affect the surgical protocol results, such as implant-prosthetic virtual plan, surgical model matching, intra or post-operative complications, time rate between surgical procedure and prosthetic loading, zygomatic implant survival rate and implant success rate were analyzed. PATIENTS AND METHODS: A total of 20 zygomatic implants were placed in atrophic maxillae of 5 patients. The final position of zygomatic implants after surgery was compared with the pre-operative digitally planned position.  The analyzed parameters were zygomatic implants apex and base mean linear distance and zygomatic implants axis mean angular deviation. RESULTS: The comparison was provided by a tridimensional imaging elaboration platform, provided by Geomagic, which allows the overlay of virtual plan STL data with post-operative control CT scan DICOM data. As a result, all the mean values regarding the 20 placed zygomatic implants respected the universally agreed values in guided zygomatic implant surgery: the mean linear distance of the implant platform and of the implant apex were 1.59 mm and 1.62 mm respectively, while the mean angular deviation of the implant axis was equal to 1.74°. One of the patients had mucositis as a post-operative complication. In one patient the anterior wall of the maxillary sinus fractured, and in one zygomatic implant primary stabilization was not achieved. No other complications occurred. CONCLUSIONS: As a conclusion, data obtained from this study suggested that guided zygomatic implant rehabilitation may represent a reliable, efficient, rapid, ergonomic, and safe surgical protocol, however further investigations are needed.

Immune-related adverse events as potential surrogates of immune checkpoint inhibitors' efficacy: a systematic review and meta-analysis of randomized studies.

BACKGROUND: Immune-related adverse events (irAEs) are frequently reported during immune checkpoint inhibitor (ICI) therapy and are associated with long-term outcomes. It is unknown if the irAE occurrence is a valid surrogate of ICIs' efficacy. METHODS: We identified articles reporting the results of randomized trials of experimental ICI therapy in solid tumors with a systematic search. The control arms could be placebo, cytotoxic/targeted therapy, or ICI therapy. We extracted the hazard ratios for overall survival (OS) with the number of OS events per arm and the number and percentages of overall and specific irAEs of grade 1-2 and grade 3-4 per arm. We estimated the treatment effect on the potential surrogate outcome with the odds ratio of the irAE rate between the experimental and the control arm. The statistical analysis consisted of weighted linear regression on a logarithmic scale between treatment effects on irAE rate and treatment effects on OS. RESULTS: Sixty-two randomized trials were included for a total of 79 contrasts and 42 247 patients. The analyses found no significant association between the treatment effects for overall grade 1-2 or grade 3-4 irAE rates or specific (skin, gastrointestinal, endocrine) irAE rates. In the non-small-cell lung cancer (NSCLC) trial subset, we observed a negative association between treatment effects on overall grade 1-2 irAEs and treatment effects on OS in studies with patients selected for programmed death-ligand 1 expression (R2 = 0.55; 95% confidence interval 0.20-0.95; R = -0.69). In the melanoma trial subset, a negative association was shown between treatment effects on gastrointestinal grade 3-4 irAEs and treatment effects on OS in trials without an ICI-based control arm (R2 = 0.77; 95% confidence interval 0.24-0.99; R = -0.89). CONCLUSIONS: We found low-strength correlations between the ICI therapy effects on overall or specific irAE rates and the treatment effects on OS in several cancer types.

Serotonin Type 2a Receptor in the Prefrontal Cortex Controls Perirhinal Cortex Excitability During Object Recognition Memory Recall.

Previous experiences can drive adaptive behavior based on different characteristics, including contextual ones. Indeed, contextual information can be used as a criterion to guide the recall of the most relevant memory trace and the inhibition of others. The medial Prefontal Cortex (mPFC) has been proposed as an area that plays a pivotal role in regulating the retrieval of memory traces in downstream regions. Also, we have shown that mPFC Serotonin 2a Receptors (5-HT2aR) modulates the retrieval of a contextually guided recognition memory task and modulates the retrieval and reconsolidation of memories in the Perirhinal Cortex (PRH). However, how the mPFC output mediated by the 5-HT2aR activity is modulating memory retrieval in the PRH is a question that remains unclear. To tackle this question, we analyzed neuronal activity in the PRH and mPFC, by measuring expression of the immediate early gene c-Fos. We combined behavioral, pharmacological and immunohistochemical techniques to examine how mPFC 5-HT2aR controls mPFC and the PRH activity. We found that blockade of mPFC 5-HT2aR increase the level of c-Fos expression in the PHR and that this increase correlates with animals' performance in the task. We also found an increase in c-Fos expression in the mPFC after mPFC 5-HT2aR blockade that does not correlate with the animals' behavioral response. However, these changes showed a significant correlation with those observed in the PRH. These results suggest that mPFC 5-HT2aR signaling may modulate the behavioral response during memory recall by controlling the neuronal activation in the PRH.

Ultra-rapid and automatic interplay between L1 and L2 semantics in late bilinguals: EEG evidence.

Converging behavioral and neuroimaging evidence suggests parallel activation of native (L1) and second (L2) language codes in bilinguals, with the modulation of the N400 as the most likely neural correlate of such L1-L2 interplay at lexico-semantic level. However, this relatively late effect may reflect secondary controlled processes, in contrast to earlier modulations found in monolinguals (<200 msec) indicative of fast and automatic lexico-semantic L1 access, which has so far not been documented for bilingualism. To address this, we investigated early neurophysiological crosslinguistic activation during bilingual word access. EEG signals were recorded from a group of late bilinguals during a masked-priming crosslinguistic task in which L1 (Russian) words were presented as subliminal primes for 50 msec before L2 (English) target words. Prime-target pairs matched either phonologically only, semantically only, both phonologically and semantically, or did not match. Cluster-based random permutation analyses revealed a main effect of semantic similarity at 40-60 msec over centro-posterior scalp sites, reflecting a negative-going shift of ERP amplitudes for semantically similar prime-target pairs. Importantly, neural source reconstruction showed activations within a left-hemispheric network comprising the middle and superior temporal cortex and the angular gyrus as the most likely neural substrate of this early semantic effect. Furthermore, analyses also revealed significant differences over frontocentral sites for the main effect of semantic and phonological similarity, ranging from 312 to 356 and 380-444 msec respectively, thus confirming previously described N400 crosslinguistic effects. Our findings confirm the existence of an integrated brain network for the bilingual lexicon and reveal the earliest (∼50 msec) crosslinguistic effect reported so far, suggesting fast and automatic L1-L2 interplay, followed by later (possibly top-down controlled) processing stages.

Sleep-disordered breathing in the otorhinolaryngological practice.

Sleep-disordered breathing (SDB) is a common disorder in childhood. Snoring and obstructive sleep apnea represents a demanding challenge for both paediatricians and otolaryngologists. This real-life study investigated the association of demographic and clinical factors on snoring and sleep apnea in children consecutively visited. In this study, 1,002 children (550 males, mean age 5.77 + 1.84 years), complaining upper airway symptoms, were prospectively enrolled during 2015-2017. Medical history, clinical examination, and fiberoptic nasopharyngoscopy were performed in all children. Tonsil hypertrophy significantly predicted sleep apnea (OR 95.08) and snoring (OR 5.44). Asthma comorbidity significantly predicted snoring (OR 2.26). Breastfeeding could be a protective factor for sleep apnea (OR =0.37). SDB is a frequent disorder observable in otorhinolaryngological practice. Tonsil hypertrophy and asthma could be considered predicting factors for both snoring and sleep apnea, whereas breastfeeding was a protective factor for SDB.

Reconciling Assumptions in Bottom-Up and Top-Down Approaches for Estimating Aerosol Emission Rates From Wildland Fires Using Observations From FIREX-AQ.

Accurate fire emissions inventories are crucial to predict the impacts of wildland fires on air quality and atmospheric composition. Two traditional approaches are widely used to calculate fire emissions: a satellite-based top-down approach and a fuels-based bottom-up approach. However, these methods often considerably disagree on the amount of particulate mass emitted from fires. Previously available observational datasets tended to be sparse, and lacked the statistics needed to resolve these methodological discrepancies. Here, we leverage the extensive and comprehensive airborne in situ and remote sensing measurements of smoke plumes from the recent Fire Influence on Regional to Global Environments and Air Quality (FIREX-AQ) campaign to statistically assess the skill of the two traditional approaches. We use detailed campaign observations to calculate and compare emission rates at an exceptionally high-resolution using three separate approaches: top-down, bottom-up, and a novel approach based entirely on integrated airborne in situ measurements. We then compute the daily average of these high-resolution estimates and compare with estimates from lower resolution, global top-down and bottom-up inventories. We uncover strong, linear relationships between all of the high-resolution emission rate estimates in aggregate, however no single approach is capable of capturing the emission characteristics of every fire. Global inventory emission rate estimates exhibited weaker correlations with the high-resolution approaches and displayed evidence of systematic bias. The disparity between the low-resolution global inventories and the high-resolution approaches is likely caused by high levels of uncertainty in essential variables used in bottom-up inventories and imperfect assumptions in top-down inventories.

Dermoscopy as a Tool for Estimating Breslow Thickness in Melanoma. / La dermatoscopia como herramienta para inferir el Breslow del melanoma.

BACKGROUND AND OBJECTIVE: The incidence of melanoma has increased significantly, and early diagnosis is the most effective way to reduce associated deaths. Dermoscopy increases diagnostic accuracy in melanoma and analysis of dermoscopic structures can help in the estimation of tumor thickness. The aim of this study was to analyze the influence of Breslow thickness on the dermoscopic characteristics of melanoma. MATERIAL AND METHODS: Observational, cross-sectional study of patients with histologically confirmed melanoma and dermoscopic images of the tumor. The patients were divided into three groups: melanoma in situ, thin melanoma (≥ 1 mm Breslow thickness), and thick melanoma (≥ 1 mm Breslow thickness). Age, sex, tumor location, and histologic and dermoscopic characteristics were analyzed in all cases. RESULTS: We studied 215 patients: 88 with melanoma in situ, 73 with thin melanoma, and 54 with thick melanoma. The frequency of the following dermoscopic features increased with increasing Breslow thickness: the blue-white veil (p < 0.001), white shiny structures (p < 0.001), and milky-red areas (p < 0.003). Angulated lines, by contrast, became less common with increasing thickness (p < 0.002). CONCLUSIONS: Dermoscopy not only improves diagnostic accuracy for pigmented lesions but also helps in the preoperative assessment of Breslow thickness in melanoma.

Can an otorhinolaryngological visit induce the suspect of allergic rhinitis in children?

Summary: Allergic rhinitis (AR) is very frequent in childhood. AR is commonly associated with some co-morbidities and typical clinical features. This study aimed to test the hypothesis whether an otorhinolaryngological (ORL) visit could induce the suspect of AR. Globally, 1,002 children (550 males, mean age 5.77 years) were consecutively visited at an ORL clinic. Clinical visit, nasal endoscopy, and skin prick test were performed in all patients. In particular, history investigated atopic familiarity, birth, feeding type, passive smoking, comorbidities, including asthma, respiratory infections, otitis media, respiratory sleep disorder. Endoscopy assessed the tonsil and adenoid volume, turbinate contacts, mucosal color, and nasal discharge. Univariate and multivariate analysis were performed. The study showed that 547 (54.6%) children had AR. Some parameters were predicting factor for suspecting AR: middle turbinate contact (OR = 9.27), familial atopy (OR = 6.24), pale nasal mucosa (OR = 4.95), large adenoid volume (OR = 3.02 for score 4), and asthma co-morbidity (OR = 2.95). In conclusion this real-life study showed that during an ORL visit it is possible to suspect AR in children with turbinate hypertrophy, familial atopy, nasal pale mucosa, adenoid enlargement, and asthma comorbidity.

Reducing complications and overall healthcare costs of hip fracture management: a retrospective study on the application of a Diagnostic Therapeutic Pathway in the Cosenza General Hospital.

BACKGROUND: Diagnostic Therapeutic Pathways (DTPs) are multidisciplinary plans designed by each healthcare organization for a specific category of patients to reduce the variability of professional behaviors and to ensure greater safety and better overall healthcare outcomes. Hip fractures are a frequent traumatic injury, particularly in the elderly, and DTPs recommend early surgical intervention, often not done due to organizational challenges and bureaucracy. Medical conditions suggesting a delay are not frequent, however long waiting times not only increase the risk of complications and mortality, but also increase the number of diagnostic test and physician consultations. This study tried to understand the benefits of performing surgical intervention within 48 hours in terms of cost savings, reduction of complications and better overall outcomes. We performed statistical analyses on data gathered from 130 patients submitted to DTPs, and we evaluated the benefits obtained by operating within 48 hours in terms of resource saving (number of physician consultations, hospitalization days, etc.), reduction in complications reported in the literature. METHODS: About 40% of clinical records of femoral fractures from 2015 at the Cosenza General Hospital were used in our statistical analysis taking into account independent variables such as age, sex,surgery waiting times and ASA (e.g. American Society of Anesthesiologists) score. Additionally, dependent variables such as: the type of complications during the hospital stay (e.g. infections, delirium, etc), days of hospitalization, and number of physician consultations were considered. RESULTS: The average waiting time for surgical intervention was 5.48 days (132 hr). Patients with ASA score of 4 had a greater chance of complications (p-value 0.03), whereas patients operated within 48 hours avoided complications, and spent fewer days in the hospital. The ASA score value correlated positively with the number of physician consultation, as the ASA score increased in number, so did the number of physician consultations. Moreover, each additional day of waiting increased the possibility of physician consultation by approximately 13. CONCLUSION: The lack of available hospital beds and staff shortages are the main reasons for the delay in performing surgery, this situation does not allow an efficient treatment and timely release of patients from the healthcare system. Therefore, there is an important need to implement standardized orthopedic and geriatric pathways (DTPs), inspired by the collaboration between healthcare system management, orthopedic and geriatric specialists, and physical therapists, to drive shorter days of hospitalization and better overall patient health outcome by performing surgery as soon as possible.

Could routine spirometry suggest sensitisation in the military medicine setting?

INTRODUCTION: Providing evidence of sensitisation is the formal requirement for allergy diagnosis. The aim of this study was to evaluate whether spirometry may be able to predict sensitisation in a representative cohort of Italian Navy military personnel. METHODS: 2043 (1875 men, 168 women, mean age 28.35±11.6 years) Italian Navy military personnel were enrolled into this study. Spirometry and skin prick testing were performed to predict sensitisation. RESULTS: Sensitisation, assessed by skin prick test, was documented in 658 (32.2%) subjects. Impaired forced expiratory flow at the 25% and 75% of the pulmonary volume (FEF25-75) as demonstrated on spirometry was detected in 82 subjects, of whom 69 were sensitised (P<0.0001). Impaired FEF25-75 was significantly associated with sensitisation (OR 7.43; 95% CI 4.04 to 14.66; P<0.0001). DISCUSSION: The findings of this study suggest that impaired FEF25-75 may predict sensitisation in this cohort of Italian Navy personnel. This outcome is relevant in the military medical setting, as it could allow early identification of subjects with subclinical asthma.

The application of the Diagnostic Therapeutic Care Pathway for the geriatric patient with anemia at the hospital of Cosenza, Italy: a management tool or a quality project?

BACKGROUND: Many studies in literature, indicate that the prognosis of hospitalized elderly patients is substantially related to the presence of concomitant diseases (multi-morbidity) along with physical, cognitive, biological and social functional impairments. These patients, therefore, require the expertise of a multi-professional and multi-disciplinary team operating in a Multi Dimensional Rating (MDR). MDR explores the multiple facets of the elderly and it is considered the tool of choice to define prognosis, especially in the case of compromised elderly patients with clinical or functional problems. MDR is satisfactory and it can be applied if it is included in a diagnostic therapeutic care pathway, which is a management tool that achieves best practices and efficiency in healthcare professionals that learn from each other. METHODS: Considering that about 80% of elderly patients has anemia, a condition often underestimated, it has been necessary to create a Diagnostic and Therapeutic Care Pathway (DTCP) with the goal to increase the level of medical awareness on this specific medical problem, and outline clear care paths for the patient. The DTCP in question was promoted by the Geriatric ward of Cosenza's Hospital by setting up a multidisciplinary working group and editing an algorithm. Indicators and standards were chosen to evaluate performance and procedures: all this has required several meetings and counseling sessions between the coordinator of DTCP and the Quality and Accreditation Operative Unit (OU). The verification of the path activities has been realized by examining the documented evidence produced. RESULTS: Preparing the indicators and standards for anemia, DTCP was a particularly challenging step of the work. DTCP has been correctly applied to more than 50% of cases, but was inapplicable to patients who either were very sick or had a very mild form of anemia. CONCLUSION: The analysis of this first phase shows that DTCP is both beneficial to the patient (framed and accompanied in her/his hospitalization and subsequent follow-up) and it facilitates the work of the physician. However, there are some limitations in its application because it is not always possible to measure indicators in every ward that participates in the DTCP.

Subgroups of multiple sclerosis patients with larger treatment benefits: a meta-analysis of randomized trials.

BACKGROUND AND PURPOSE: No subgroups of patients with higher treatment effects have been clearly detected in multiple sclerosis (MS). The aim of the present work was to evaluate whether there are subgroups of relapsing-remitting MS (RRMS) patients who are more responsive to treatments. METHODS: All published randomized clinical trials in RRMS reporting a subgroup analysis of treatment effect were collected. Two main outcomes, the annualized relapse rate (ARR) and the disability progression, were studied. The treatment effect in each subgroup was reported as a relative effect (RE), defined as the treatment effect in the subgroup relative to the overall effect. A meta-analysis was run to compare the RE between subgroups. RESULTS: Six trials (6693 RRMS patients) were included. Treatment effects on ARR were significantly higher in younger than in older subjects (RE = 0.83 vs. RE = 1.30, P < 0.001), in patients with than those without gadolinium activity (RE = 0.86 vs. RE = 1.15, P = 0.005) and in patients with lower than in those with higher Expanded Disability Status Scale (RE = 0.96 vs. RE = 1.23, P = 0.02), and on disability progression in younger than in older subjects (RE = 0.82 vs. RE = 1.28, P = 0.017). CONCLUSIONS: This study formally shows that in RRMS higher treatment effects are associated with characteristics of earlier (lower age and Expanded Disability Status Scale) and more active (higher gadolinium activity) disease.

Oculo-facio-cardio-dental (OFCD) syndrome: the first Italian case of BCOR and co-occurring OTC gene deletion.

Oculo-facio-cardio-dental (OFCD) syndrome is a rare genetic disorder affecting ocular, facial, dental and cardiac systems. The syndrome is an X-linked dominant trait and it might be lethal in males. This syndrome is usually caused by mutations in the BCL6 interacting co-repressor gene (BCOR). We described a female child with mild phenotype of oculo-facio-cardio-dental syndrome. Array-comparative genomic hybridization (a-CGH) analysis revealed a de novo heterozygous deletion in the Xp11.4 region of approximately 2.3 Mb, involving BCOR and ornithine carbamoyl-transferase (OTC) genes. The deletion observed was subsequently confirmed by real time PCR. In this study we report a first case with co-occurrence of BCOR and OTC genes completely deleted in OFCD syndrome.

New High-performance Liquid Chromatography-DAD Method for Analytical Determination of Arbutin and Hydroquinone in Rat Plasma.

Natural substances present in herbal preparations should be carefully used because they can give toxic or therapeutic effects despite of their amount or the way of administration. The safety of products of vegetable origin must be assessed before commercialisation by monitoring the active ingredients and their metabolites. This study was therefore designed to identify and quantify arbutin and its metabolite hydroquinone, naturally present in Arctostaphylos uva-ursi (L.) Spreng plant in rat plasma, after an acute and subacute administration of aqueous arbutin solution in Wistar rats. For this purpose a reversed-phase high-performance liquid chromatography coupled with photodiode array detection was developed to assess the pharmacokinetic of arbutin and hydroquinone in plasma of female rats treated with aqueous arbutin solutions. The detection (arbutin: 0.0617 µg/ml and hydroquinone 0.0120 µg/ml) and quantification (arbutin: 0.2060 µg/ml and hydroquinone: 0.0400 µg/ml) limits were determined. At the arbutin concentration level of 10.7 µg/ml repeatability was 13.33% and its recovery 93.4±6.93%, while at the hydroquinone concentration level of 10.6 µg/ml repeatability was 11.66% and its recovery 92.9±7.75%. Furthermore the method was fully validated and the obtained data indicate that the new method provides good performances.

[Use of progesterone-releasing intra-uterine system in menhorragia relapse prevention after laparoscopic myomectomy]. / Impiedo della spirale medicate al progesterone nella prevenzione delle recidive menorragiche dopo miomectomia laparoscopica.

AIM: Abnormal uterine bleeding (AUB) affects about 30% of women in childbearing age with negative impact on patient's quality of life and uterine myomas represent one of the major cause of AUB. Laparoscopic myomectomy has proven to be efficient to reduce uterine bleeding and pelvic pain, but some patients presents postsurgery menhorragia with anemia. To reduce it, the combined use of levonorgestrel releasing intrauterine system (LNG-IUS) positioned at the end of surgery, seems to produce a clinically relevant decrease in AUB with a symptomatology improvement. The aim of this study was to retrospectively evaluate if postsurgery placement of LNG-IUS improves hematological outcomes (hemoglobin and ferritin level) in woman submitted to laparoscopic myomectomy. METHODS: We retrospectively collected data from 58 women who underwent laparoscopic myomectomy from September 2010 to September 2011. Twenty-six patients were treated by laparoscopic myomectomy followed by LNG-IUS positioning at the end of surgery (Experimental group) and thirty-two patients were treated by surgery alone (Control group). We compared blood hemoglobin and ferritin levels assessed preoperatively, in day one and 6, 12 and 18 months after surgery. RESULTS: There was a statistically significant improvement in terms of post-surgery hemoglobin and ferritin levels at 6 month follow up (P=0.02 and P=0.002 respectively) and 12 month follow-up (P=0.001 and P=0.001, respectively) in experimental group vs. control group and a positive trend, but not statistically significant, in ferritin levels at 18 month-follow-up (P=0.1). CONCLUSION: Our data suggest that combined treatment with laparoscopic myomectomy followed by LNG-IUS produces a clinically relevant improvement in hematological values.

The clinical and molecular characterization of patients with dyshormonogenic congenital hypothyroidism reveals specific diagnostic clues for DUOX2 defects.

CONTEXT: Mutations in the DUOX2 gene have been associated with transient or permanent congenital hypothyroidism due to a dyshormonogenic defect. OBJECTIVE: This study aimed to verify the prevalence of DUOX2 mutations and the associated clinical features in children selected by criteria supporting a partial iodide organification defect (PIOD). PATIENTS AND METHODS: Thirty children with PIOD-like criteria were enrolled and genotyped. A detailed clinical characterization was undertaken together with the functional analysis of the DUOX2 variations and the revision of the clinical and molecular data of the literature. RESULTS: In this large selected series, the prevalence of the DUOX2 mutations was high (37%). We identified 12 missense variants, one splice site, and three frameshift DUOX2 mutations. Functional analyses showed significant impairment of H2O2 generation with five missense variants. Stop-codon mutants were shown to totally abolish DUOX2 activity by nonsense-mediated RNA decay, exon skipping, or protein truncation. DUOX2 mutations, either mono- or biallelic, were most frequently associated with permanent congenital hypothyroidism. Moreover, the present data suggested that, together with goiter and PIOD, the most significant features to select patients for the DUOX2 analysis are the low free T4 and the high TSH concentrations at the first postnatal serum sampling, despite borderline blood spot TSH. Interestingly, the analysis of previously described DUOX2 mutated cases confirmed the validity of these findings. CONCLUSIONS: The defects in the peroxide generation system are common among congenital hypothyroidism patients with PIOD. The most robust clinical parameters for selecting patients for DUOX2 analysis have been identified, and several DUOX2 variants have been functionally characterized.