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.

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.

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.

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.

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.

The reciprocal link between sleep and immune responses.

Good sleep is necessary for both physical and mental health; sleep and immune responses are reciprocally and closely linked. Sleep loss impairs the immune response, while, on the other hand, the immune response, activated for instance by an infection, alters sleep. Sleep alterations induced by immune activation are mediated by cytokines such as interleukin-1. In the past, it was thought that cytokines were produced only by the immune system, and active only there as signaling molecules. Today it is clear that IL-1 and other cytokines are present and active in the healthy brain, where they physiologically interact with the brain circuits and the neurotransmitter systems (for instance the serotonergic, GABAergic, and cholinergic systems) that control sleep. These interactions are altered by immune response, and, as a result, non-rapid eye movement (NREM) sleep is increased and fragmented, whereas rapid eye movements (REM) sleep is inhibited.

Stem Cell Therapy for Male Urinary Incontinence.

INTRODUCTION: Among the medical and surgical options which have been proposed in the last years for the management of male stress urinary incontinence (SUI), stem cell therapy represents a new frontier treatment. The aim of this paper is to update the current status of stem cell therapy in animal and human studies for the management of iatrogenic male SUI. MATERIAL AND METHODS: A PubMed review of the literature on stem cell therapy for the treatment of male SUI was performed. RESULTS: Regarding animal studies, bone marrow-, muscle- and adipose-derived stem cells have been widely studied, showing regeneration of the urethral sphincter and recovery of the damaged pelvic nerves. With regard to human studies, only four papers are available in the literature using muscle- and adipose-derived stem cells which reported a significant improvement in sphincteric function and incontinence with no severe side effects. CONCLUSIONS: In spite of these promising results, further studies are needed with longer follow-ups and larger numbers of patients in order to clarify the potential role of stem cell therapy for the treatment of male SUI.

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.

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.

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.

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.

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.

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.

Early results of urothelial carcinoma screening in a risk population of coke workers: urothelial carcinoma among coke workers.

OBJECTIVE: To present the protocol and the early results of a urothelial carcinoma (UC) screening analysis performed in a risk population of coke workers. METHODS: Between June 2006 and October 2008, 171 male workers (mean age 43 years), employed in a Ligurian coke plant (Italiana Coke S.r.l) and exposed to polycyclic aromatic hydrocarbons (PAHs) for a median period of 16 years, underwent screening for UC. Urological evaluation included medical history, physical examination, routine laboratory tests, urine analysis, urinary cytology and uCyt+ assay. In the event of signs and symptoms suggestive of UC or positive urinary tests, the workers were also subjected to urinary ultrasonography and cystoscopy with biopsy of any suspicious lesions. RESULTS: Regarding the laboratory tests, 19/171 (11%) uCyt+ samples were considered inadequate and were excluded from the outcomes assessment. Overall, urine analysis, cytology and uCyt+ were positive in 18/152 (12%) subjects who showed no evidence of UC at the scheduled check-ups. No significant association was identified between marker positivity and occupational activity. CONCLUSIONS: Our results fail to show an increased risk of UC among the coke workers evaluated. However, they will need to be confirmed in the future by a larger enrollment and a longer follow-up in order to assess the definitive risk for UC after exposure to coke.

[Preoperative and postoperative management of adrenal masses]. / Terapia medica pre e post-operatoria della patologia espansiva surrenalica.

The surgical approach of adrenal masses requires a careful preoperative and postoperative management. In order to avoid iatrogenic hypocortisolism, Cushing patients have to be treated, before adrenal surgery and then every eight hours, with hydrocortisone 100 mg iv. The therapy should be gradually reduced to 10-20 mg/die by mouth for six-twelve months. In primary hyperaldosteronism the target of medical treatment is to control blood pressure and serum potassium values as well as to normalize the circulating aldosterone levels or to obtain mineralocorticoid receptor blockade. Epleronone and spironolactone are the most common used drugs. Spironolactone has long been the drug of choice while epleronone represents a newer more expensive alternative with fewer side effects. Postoperative management generally does not require steroid replacement therapy. The management of pheochromocytoma requires a careful medical preparation for surgery: in fact, the surgical removal of a pheochromocytoma is a high-risk procedure and an experienced surgeon/anesthesiologist team is required. The preoperative medical therapy is aimed at controlling hypertension (including preventing a hypertensive crisis during surgery) and at avoiding cardiac arrhythmia. The most common used drugs are alpha-adrenergic blockade: phenoxybenzamine is an irreversible, long-acting, nonspecific alpha-adrenergic blocking agent. Doxazosine is a selective alpha1-adrenergic blocking agent with a more favorable side-effect profile, being less related to postoperative hypotension. Postsurgical management is aimed at expanding plasma volume: a copious hydration is required while the use of dopamine in hemodynamin support is not effective because of the preoperative use of alpha-blocking agents.

Assessing long-run economic benefits attributed to an IVF-conceived singleton based on projected lifetime net tax contributions in the UK.

BACKGROUND: Over the past decade, demand for fertility treatments has increased as a result of delaying time to first pregnancy and growing awareness and acceptance of available treatment options. Despite increasing demand, health authorities often view infertility as a low health priority and consequently limit access to treatments by rationing and limiting funds. METHODS: To assess the long-term economic benefits attributed to in vitro fertilization (IVF)-conceived children, we developed a health investment model to evaluate whether state-funded IVF programmes in the UK represent sound fiscal policies. Based on the average investment cost to conceive an IVF singleton, we describe the present value of net taxes derived from gross taxes paid minus direct government transfers received (e.g. education, health, pension) over the lifetime of the child. To establish the present value of investing in IVF, we have discounted all costs from benefits (i.e. lifetime taxes paid) using UK Treasury department rates based on a singleton delivery with similar characteristics for education, earnings, health and life expectancy to a naturally conceived child. RESULTS: The lifetime discounted value of net taxes from an IVF-conceived child with mother aged 35 is pound 109,939 compared with pound 122,127 for a naturally conceived child. The lifetime undiscounted net tax contribution for the IVF-conceived child and naturally conceived child are pound 603,000 and pound 616,000, respectively. CONCLUSIONS: An investment of pound 12,931 to achieve an IVF singleton is actually worth 8.5-times this amount to the UK Treasury in discounted future tax revenue. The analysis underscores that costs to the health sector are actually investments when a broader government perspective is considered over a longer period of time.