Does social distancing impact pediatric upper airway infections? An observational controlled study and a brief literature review.

PURPOSE: SARS-CoV-2 pandemic has reduced social interaction even among children. The objective of the study was to assess the role of social distancing in the course of common pediatric upper airway recurrent diseases. MATERIALS AND METHODS: Patients aged ≤14 years with at least one ENT-related clinical condition were retrospectively recruited. All patients had two outpatient evaluations in the same period (April - September): the control group had the first evaluation in 2018 and second in 2019, whereas the case group had the first evaluation in 2019 and second in 2020. Patients of each group were individually compared between their two visits and deemed improved/unchanged/worsened for each specific ENT condition. The percentage of children improved/unchanged/worsened were then collectively compared between the two groups for each condition. RESULTS: Patients who experienced social distancing presented a significantly higher improvement rate than controls for recurrent acute otitis media episodes (35.1 % vs. 10.8 %; Fisher's exact test p = 0.033) and for tympanogram type (54.5 % vs. 11.1 %, Fisher's exact test p = 0.009). CONCLUSIONS: The anti-contagion social restrictions decreased the prevalence of middle ear infections and effusion in children. Further studies on larger cohorts are required to better elucidate these findings.

Factors affecting prognosis in locoregional recurrence of oral squamous cell carcinoma.

BACKGROUND: Recurrence of oral squamous cell carcinoma (rOSCC) after primary treatment is associated with poor survival outcomes. Salvage treatment with further surgery, radiotherapy and chemotherapy has high morbidity, making patient selection crucial. However, in the recurrence setting, reliable stratification data are scarce. Decision-making in this context is consequently complex. We investigated factors influencing overall survival after rOSCC. METHODS: Retrospective cohort study of patients with rOSCC (n = 83) at the Queen Elizabeth Hospital Birmingham, UK between 2006 and 2016. Associations with overall survival were analysed using univariate and multivariate analyses to identify important clinical prognostic indicators. RESULTS: Overall survival at 1 year was 32.5% and at 5 years was 18.1% after a median follow-up of 7.4 months. Multivariate analysis identified four independent predictors of overall survival following rOSCC: size of primary tumour (HR 2.077; 95% CI 1.034-4.172), extent of recurrent disease (HR 3.286; 95% CI 1.545-6.991), history of moderate alcohol consumption (HR 0.351; 95% CI 0.162-0.763), and close or positive margins at primary resection (HR 1.955; 95% CI 1.063-3.595). CONCLUSIONS: We identified four key factors that help prognostication and risk stratification of rOSCC. Given the high morbidity associated with salvage treatment, we recommend that the multidisciplinary team (MDT) and the patient weigh these factors carefully when considering further treatment. Further investigation of the biology underlying these oncophenotypes may contribute to better patient stratification.

Quality of life after laparoscopic sigmoid resection for uncomplicated diverticular disease.

PURPOSE: The study aimed to evaluate the QoL in patients who underwent elective surgery for uncomplicated diverticulitis using a recently developed diverticulitis quality of life questionnaire (DV-QoL). METHODS: All consecutive patients who underwent surgery for uncomplicated diverticulitis or who were hospitalized and treated conservatively for acute uncomplicated diverticulitis episodes in three referral centers, in a 5-year period, were included in the study. The 36-Item Short Form Survey and the DV-QoL were administered to the patients to assess their QoL before and after treatment of diverticular disease. RESULTS: Ninety-seven patients who underwent surgery, 44 patients who were treated conservatively, and 44 healthy volunteers were included in the study. DV-QoL scores correlated with SF-36 scores (p < 0.0001). The surgically treated patients reported a worse quality of life before treatment with respect to the patients treated conservatively (mean 21.12 surgical vs 15.41 conservative, p = 0.0048). The surgically treated patients presented better post-treatment global scores with respect to the conservatively treated patients (mean: 6.90 surgical vs 10.61 conservative, p = 0.0186). Covariance analysis confirmed that the differences between the pre- and post-treatment DV-QoL scores were significantly higher in the surgical (p = 0.0002) with respect to the non-surgical patients. As far as single items were concerned, differences between the two groups were found in the pre- and post-treatment "concerns" and "behavioral changes" DV-QoL items. CONCLUSIONS: Sigmoidectomy reduces concerns about diverticulitis and behavioral changes due to the disease. Quality of life should be considered when referring patients with uncomplicated diverticulitis to surgery. Prospective studies are required to confirm this result.

Italian version of the Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS): validation and longitudinal performance.

OBJECTIVE: To validate an Italian version of the Rasch-Built Overall ALS Disability Scale (ROADS) in a broad population of patients and assess its longitudinal performance over time. METHODS: 270 ALS patients referring to the Motor Neuron Disease Clinic of the University of Padova and Modena (Italy) accepted to compile the Italian version of the ROADS and results were correlated with the ALSFRSr and ALSAQ-40 scores, FVC values, and creatinine or albumin blood levels. To verify test-retest reliability, patients were asked to fill in a second copy of the scale within 5-7 days. Thirty-nine patients compiled a further copy of questionnaire during the follow up visit (after 133 days on average) which allowed us a longitudinal assessment of the scale. RESULTS: We found a good external construct validity between ROADS and either ALSFRS-R (correlation coefficient = 0.85) or ALSAQ-40 (correlation coefficient = - 0.84). Test-retest reliability was excellent with a concordance-correlation coefficient of 0.93. Yet, we observed a significant correlation between changes over time of the ROADS normalised sum score (- 2.18 point loss per month) and those of both the ALSFRS-R (positive correlation; Rho = 0.64, p ≤ 0.0001) or the ALSAQ-40 (negative correlation; Rho = - 0.60, p = 0.014). CONCLUSIONS: The Italian version of ROADS proved to be a reliable marker to monitor overall disability in ALS patients. Further studies are necessary to assess its longitudinal performance.

Tooth retention predicts good physical performance in older adults.

BACKGROUND: Oral health is closely related to both physical and psychological well-being, as it enables individuals to eat, speak, and socialize. The number of teeth is the most used indicator of oral health. Several reports document a relationship of dental status with a variety of indicators of general health but longitudinal studies employing standardized physical performance tests are infrequent in the scientific literature. SUBJECTS AND METHODS: The Italian elderly participating in the Pro.V.A. longitudinal Study (3099 subjects aged 65+ at baseline, 2196 at the 5-year follow-up 1 and 1641 at the 7-year follow- up 2) underwent detailed interview and extensive clinical and instrumental examination that included validated physical performance measures. Participants were classified into 4 groups according to the number of remaining teeth: 0, 1-7, 8-19, and 20+. To explore the association of the number of remaining teeth with physical function and disability, we performed logistic regression analyses with models progressively adjusted for a wide number of covariates, namely anthropometric (gender, age, BMI), comorbidity (cardio-vascular, osteoarticular, and neurological diseases including depression), muscle strength (assessed for upper and lower limbs), lifestyle (smoking status, alcohol use, leisure time activities) and socioeconomical status (education, income, marital status, loneliness). RESULTS: Dental status correlated with most comorbidities, lifestyle, and socio-economic variables at the univariate analysis at baseline and at follow-ups. A good dental status was significantly associated with better physical functioning and lower disability. The presence of 20+ teeth resulted significantly protective (reference group: 0 teeth) versus mobility-related disability (OR = 0.67), disability (OR = 0.54) and inability to perform heavy duties (OR = 0.62), at follow up 1 and low physical performance score (OR = 0.59) at follow up 2. Conversely, the detrimental effect of edentulism, explored in subjects with or without dentures, was present but not as straightforward. Conclusion. The assessment of a geriatric patient should include an oral evaluation as a good dental status is a crucial component of successful aging.

The hazard of (sub)therapeutic doses of anticoagulants in non-critically ill patients with Covid-19: The Padua province experience.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is responsible for a worldwide pandemic, with a high rate of morbidity and mortality. The increasing evidence of an associated relevant prothrombotic coagulopathy has resulted in an increasing use of antithrombotic doses higher than usual in COVID-19 patients. Information on the benefit/risk ratio of this approach is still lacking. OBJECTIVE: To assess the incidence of relevant bleeding complications in association with the antithrombotic strategy and its relationship with the amount of drug. METHODS: Consecutive COVID-19 patients admitted between February and April 2020 were included in a retrospective analysis. Major bleedings (MB) and clinically relevant non-major bleeding (CRNMB) were obtained from patient medical records and were adjudicated by an independent committee. RESULTS: Of the 324 patients who were recruited, 240 had been treated with prophylactic doses and 84 with higher doses of anticoagulants. The rate of the composite endpoint of MB or CRNMB was 6.9 per 100-person/months in patients who had been given prophylactic doses, and 26.4 per 100-person/months in those who had been prescribed higher doses (hazard ratio, 3.89; 95% confidence interval, 1.90-7.97). The corresponding rates for overall mortality were 12.2 and 20.1 per 100-person/months, respectively. CONCLUSIONS: The rate of relevant bleeding events was high in patients treated with (sub)therapeutic doses of anticoagulants. In the latter group, overall mortality did not differ from that of patients treated with standard prophylactic doses and was even higher. Our result does not support a strategy of giving (sub)therapeutic doses of anticoagulants in non-critically ill patients with COVID-19.

Effects of an antimicrobial stewardship intervention on perioperative antibiotic prophylaxis in pediatrics.

Purpose: This study aims to determine the effectiveness of an Antimicrobial Stewardship Program based on a Clinical Pathway (CP) to improve appropriateness in perioperative antibiotic prophylaxis (PAP). Materials and methods: This pre-post quasi-experimental study was conducted in a 12 month period (six months before and six months after CP implementation), in a tertiary Pediatric Surgical Centre. All patients from 1 month to 15 years of age receiving one or more surgical procedures were eligible for inclusion. PAP was defined appropriate according to clinical practice guidelines. Results: Seven hundred sixty-six children were included in the study, 394 in pre-intervention and 372 in post-intervention. After CP implementation, there was an increase in appropriate PAP administration, as well as in the selection of the appropriate antibiotic for prophylaxis, both for monotherapy (p = 0.02) and combination therapy (p = 0.004). Even the duration of prophylaxis decreased during the post-intervention period, with an increase of correct PAP discontinuation from 45.1 to 66.7% (p < 0.001). Despite the greater use of narrow-spectrum antibiotic for fewer days, there was no increase in treatment failures (10/394 (2.5%) pre vs 7/372 (1.9%) post, p = 0.54). Conclusions: CPs can be a useful tool to improve the choice of antibiotic and the duration of PAP in pediatric patients.

Acute rejection in kidney transplantation and the evaluation of associated polymorphisms (SNPs): the importance of sample size.

Background Acute rejection (AR) is one of the most frequent complications after kidney transplantation (KT). Scientific evidence reports that some single-nucleotide polymorphisms (SNPs) located in genes involved in the immune response and in the pharmacokinetics and pharmacodynamics of immunosuppressive drugs are associated with rejection in renal transplant patients. The aim of this study was to evaluate some SNPs located in six genes: interleukin-10 (IL-10), tumor necrosis factor (TNF), adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1), uridine diphosphate glucuronosyltransferase family 1 member A9 (UGT1A9), inosine monophosphate dehydrogenase 1 (IMPDH1) and IMPDH2. Methods We enrolled cases with at least one AR after KT and two groups of controls: patients without any AR after KT and healthy blood donors. Genetic analysis on DNA was performed. The heterozygosity (HET) was determined and the Hardy-Weinberg equilibrium (HWE) test was performed for each SNP. The sample size was calculated using the QUANTO program and the genetic associations were calculated using the SAS program (SAS Institute Inc., Cary, NC, USA). Results In our previous preliminary study (sample size was not reached for cases), the results showed that patients with the C allele in the SNP rs1045642 and the A allele in the SNP rs2032582 of the ABCB1 gene had more frequent AR. In contrast, with the achievement of sample size, the trend of the previous data was not confirmed. Conclusions Our study highlights a fundamental aspect of scientific research that is generally presumed, i.e. the sample size of groups enrolled for a scientific study. We believe that our study will make a significant contribution to the scientific community in the discussion of the importance of the analysis and the achievement of sample size to evaluate the associations between SNPs and the studied event.

Unravelling the (arte)fact of increased pacemaker rate with the Edwards SAPIEN 3 valve.

AIMS: Early data on the Edwards SAPIEN 3 valve (S3-THV) have shown low rates of paravalvular leaks and vascular complications but relatively high 30-day permanent pacemaker implantation (PPMI) rates. No direct comparisons on clinical outcomes including PPMI rates are available for the S3-THV and the Edwards SAPIEN XT (XT-THV). We aimed to compare the 30-day PPMI rates in patients treated with the two prostheses and to assess the interplay among valve type, depth of implantation and PPMI rate. METHODS AND RESULTS: Two hundred and nine patients treated by TAVI were considered. The S3-THV was associated with higher PPMI rates compared to the XT-THV, both overall and in subgroups matched for several predictors of PPMI. However, in the S3-THV group, 30-day PPMI was strictly associated with deep valve implantation, and PPMI risk of high-implanted S3-THVs was similar to that of the overall XT-THV matched group. No cases of significant paravalvular leak were observed in the S3-THV group. CONCLUSIONS: The S3-THV was associated with a higher incidence of PPMI compared to the XT-THV. In the S3-THV group, pacemaker implantation was strictly associated with deep valve implantation. An implantation technique involving higher initial placement of the central marker (from 0 to 3 mm above the base of the aortic cusps) and, as a consequence, higher final valve depth might help in preventing post-TAVI PPMI with the S3-THV, without affecting the risk of paravalvular leak.

Muscle MR imaging in tubular aggregate myopathy.

PURPOSE: To evaluate with Magnetic Resonance (MR) the degree of fatty replacement and edematous involvement in skeletal muscles in patients with Tubular Aggregate Myopathy (TAM). To asses the inter-observer agreement in evaluating muscle involvement and the symmetry index of fatty replacement. MATERIALS AND METHODS: 13 patients were evaluated by MR to ascertain the degree of fatty replacement (T1W sequences) according to Mercuri's scale, and edema score (STIR sequences) according to extent and site. RESULTS: Fatty replacement mainly affects the posterior superficial compartment of the leg; the anterior compartment is generally spared. Edema was generally poor and almost only in the superficial compartment of the leg. The inter-observer agreement is very good with a Krippendorff's coefficient >0.9. Data show a total symmetry in the muscular replacement (McNemar-Bowker test with p = 1). CONCLUSIONS: MR reveals characteristic muscular involvement, and is a reproducible technique for evaluation of TAM. There may also be a characteristic involvement of the long and short heads of the biceps femoris. It is useful for aimed biopsies, diagnostic hypotheses and evaluation of disease progression.

Persistent increase of osteoprotegerin levels after cortisol normalization in patients with Cushing's syndrome.

OBJECTIVE: Osteoprotegerin (OPG) has been identified as a decoy receptor that inhibits osteoclast differentiation and, more recently, as a paracrine regulator of vascular calcification. OPG is suppressed by glucocorticoids (GC); however, results from experimental and clinical studies are not univocal. The aim of this study was to evaluate OPG and bone metabolism in patients with Cushing's syndrome (CS) before and after cure. DESIGN AND METHODS: Twenty-six patients with CS (all women, mean age: 39.1+/-11.9 years) and 24 age- and gonadal status-matched healthy women were studied for bone mineral density, bone metabolism, OPG, and receptor activator of nuclear factor-kB ligand at baseline. Twelve patients were also studied 6-18 months after surgery, with persistent normalization of cortisol levels. RESULTS: OPG was significantly higher and osteocalcin (OC) was significantly lower in CS patients than in controls (OPG: 4.17+/-1.23 vs 2.95+/-0.79 pmol/l, P=0.00001; OC: 15.0+/-6.1 vs 18.8+/-6.8 ng/ml, P=0.04 in CS and controls respectively). After cure, we found no difference in OPG levels, despite a significant increase in OC levels (from 16.4+/-11 to 37.2+/-15 ng/ml, P=0.03). CONCLUSION: Patients with CS showed increased OPG serum levels that remained unchanged after recovery, despite a restoration of bone formation. We speculate that high levels of OPG could reflect the persistent damage of the GCs on cardiovascular system.

Can C4d immunostaining on endomyocardial biopsies be considered a prognostic biomarker in heart transplant recipients?

BACKGROUND: The aim of this study was to assess the significance of positive C4d capillary immunostaining of endomyocardial biopsies and its correlation to clinical outcome in adult heart transplant recipients. METHODS: Nine hundred eighty-five endomyocardial biopsies from 107 heart transplant recipients were evaluated. Immunostaining for detection of intragraft C4d capillary deposition was performed on paraffin-embedded tissue using anti-human C4d polyclonal antibody. RESULTS: Positive staining of C4d was present in 36 patients (34%) and antibody-mediated rejection in eight patients (7%). The patients were subdivided into four groups on the basis of their C4d, circulating antidonor antibodies (donor-specific antibodies [DSAs]), and graft function: group 1=C4d positive, DSA negative, and no graft dysfunction; group 2=C4d positive, DSA positive, and no graft dysfunction; group 3=C4d positive, DSA positive, and signs of graft dysfunction, and group 0 (control)=all negative. An higher mortality risk was found in C4d-positive patients, when compared with negative ones (unadjusted hazard ratios: group 1: 18, group 2: 61, and group 3: 32-fold risk; P<0.0001). CONCLUSIONS: Antibody-mediated rejection is a complex and ongoing phenomenon with different phenotypic features. C4d positive predicts worse prognosis. C4d positive [corrected] and DSA can be used as early mortality predictors in patients without signs of graft dysfunction.