The international sinonasal microbiome study: A multicentre,multinational characterization of sinonasal bacterial ecology

The sinonasal microbiome remains poorly defined, with our current knowledge based on a few cohort studies whose findings are inconsistent. Furthermore, the variability of the sinus microbiome across geographical divides remains unexplored. We characterize the sinonasal microbiome and its geographical variations in both health and disease using 16S rRNA gene sequencing of 410 individuals from across the world. Although the sinus microbial ecology is highly variable between individuals, we identify a core microbiome comprised of Corynebacterium, Staphylococcus, Streptococcus, Haemophilus and Moraxella species in both healthy and chronic rhinosinusitis (CRS) cohorts. Corynebacterium (mean relative abundance = 44.02%) and Staphylococcus (mean relative abundance = 27.34%) appear particularly dominant in the majority of patients sampled. Amongst patients suffering from CRS with nasal polyps, a statistically significant reduction in relative abundance of Corynebacterium (40.29% vs 50.43%; P = .02) was identified. Despite some measured differences in microbiome composition and diversity between some of the participating centres in our cohort, these differences would not alter the general pattern of core organisms described. Nevertheless, atypical or unusual organisms reported in short-read amplicon sequencing studies and that are not part of the core microbiome should be interpreted with caution. The delineation of the sinonasal microbiome and standardized methodology described within our study will enable further characterization and translational application of the sinus microbiota.     

More optimism,less pain! The influence of generalized and pain-specific expectations on experienced cold-pressor pain

Accumulating evidence suggests that dispositional optimism might be a protective factor against experiencing pain. The current paper presents two studies investigating the association between dispositional optimism and experimental pain. Moreover, the influence of pain-specific expectations on this association is investigated. In Study 1, mediation of pain-specific expectations in the relation between dispositional optimism and pain was hypothesized. Expected and experienced pain ratings were obtained from 66 healthy participants undergoing a cold pressor tolerance task. In Study 2, the moderating effect of dispositional optimism on the association between induced pain expectations and pain reports was studied in 60 healthy participants undergoing a 1-min cold pressor task. Both studies controlled for individual differences in fear of pain. Significant associations between dispositional optimism and pain ratings were found in both studies, although the exact time point of these associations differed. Subscale analyses revealed that only the pessimism subscale contributed significantly to these findings. We found no evidence for hypothesized mediation and moderation effects. Alternative explanations for the optimism-pain association are discussed.     

Quality of life and behavioral functioning in Dutch pediatric patients with hereditary spherocytosis

The objective of this study was to evaluate health-related quality of life (HRQoL) and behavioral functioning in pediatric patients with hereditary spherocytosis (HS). A cross-sectional study was conducted in 132 Dutch children and adolescents with HS and aged 8–18 years of whom 48 underwent splenectomy prior to the study. HRQoL was assessed using the KIDSCREEN-27, and behavioral functioning was evaluated using the strength and difficulties questionnaire (SDQ). Scores of pediatric patients with HS were compared to a Dutch norm population. Additionally, the effects of three factors were assessed: fatigue, self-image, and parents’ perceived vulnerability (measured with the checklist individual strength, the self-perception profile for children and adolescents, and the child vulnerability scale). Both unsplenectomised and splenectomised pediatric patients reported lower HRQoL on the domain physical well-being (KIDSCREEN-27) compared to Dutch peers. For behavioral functioning, parents of both groups reported more emotional problems (SDQ) compared to the norm population. Pediatric patients with lower scores on physical well-being experienced more fatigue. The patients’ perceived social acceptance and parents’ perceived vulnerability appeared as determinants of emotional problems. Conclusion: Pediatric patients in the current study generally report few complaints, and the results suggest that these patients overall have a strong ability to cope with HS. Despite these few complaints, fatigue and parents’ perceived vulnerability seem to be important determinants for lower HRQoL and more emotional problems. Therefore, screening on these factors could serve as an addition to the treatment of HS, to help pediatric patients who are at risk for lower HRQoL or more emotional problems.     

Estimating adjuvant treatment effects in Stage II colon cancer: Comparing the synthesis of randomized clinical trial data to real-world data

There is an ongoing discussion regarding the impact of adjuvant chemotherapy in Stage II colon cancer. We therefore estimated adjuvant treatment effect in Stage II colon cancer using pooled disease-free survival (DFS) data from randomized clinical trials (RCT approach) and compared this to real-world data (RWD approach) estimates. First, we estimated the treatment effect in RCTs by (i) searching relevant trials reporting DFS data, (ii) generating patient-level data from reported DFS data and (iii) estimating treatment effect in the patient-level data. Second, the treatment effect was estimated in an observational cohort of 1,947 patients provided by the Netherlands Cancer Registry using three propensity score methods; matching, weighting and stratification. In the RCT approach, patient-level data of 4,489 patients (events: 853) were generated from seven trials which compared two of the following treatment arms: control, 5FU/LV or FOLFOX. A Cox model was used to estimate a hazard ratio (HR) of 0.77 (0.43;1.10) for 5FU/LV vs. control and 0.93 (0.72;1.15) for FOLFOX vs. 5FU/LV. In the RWD approach, HRs for any adjuvant treatment vs. control were 0.95 (0.50;1.80), 0.88 (0.24;3.21) and 1.05 (0.04;2.06) using matching, weighting and stratification, respectively. There was no significant difference with the estimates from the RCT approach (interaction test, p > 0.10). The RCT data suggest a clinically relevant benefit of adjuvant chemotherapy in terms of DFS, but the estimate did not reach statistical significance. Stratified analyses are required to evaluate whether treatment effect differs in specific subgroups.     

Informed choice on Pap smear still limited by lack of knowledge on the meaning of false-positive or false-negative test results

Objective

Screening for cervical cancer may have favourable or unfavourable effects at the individual level. This study assesses whether invitees in the Netherlands made an informed choice about screen uptake.

Methods

Attached to the invitation letter and the information leaflet, screen invitees were sent a questionnaire. An informed decision was defined as based on decision-relevant knowledge, while the woman's attitude was consistent with her actual screening behaviour.

Results

Of all cervical screen participants, 60% (924/1551) responded to the questionnaire. Decision-relevant knowledge was sufficient in 595 women. Especially knowledge about false-positive and false-negative test results was limited. The attitude towards cervical screening was mainly positive (99%). Requirements for informed decision making were met in 571 (68%) women and in 91% when an alternative cut-off point of sufficient decision-relevant knowledge was applied. Most frequently reported main reasons to attend were early detection of abnormalities (67%) and reassurance in case of a normal smear (22%).

Conclusion

Insufficient decision-relevant knowledge was the main cause of uninformed attendance.

Practice implication

Adequate strategies to provide invitees with sufficient decision-relevant information are still needed, especially regarding false-positive and false-negative test results.     

Sentinel lymph node biopsy performed under local anesthesia is feasible

BACKGROUND: A sentinel lymph node (SLN) biopsy in breast cancer patients, performed under local anesthesia (LA), could have advantages such as more efficient use of operating room time and pathologist time. It also provides a histologic diagnosis before definitive breast surgery is undertaken. The aim of this study was to assess feasibility by comparing the results of SLN procedures performed under LA versus general anesthesia (GA). METHODS: The SLN procedure was performed in 50 consecutive outpatients and 167 inpatients with clinical T1-2N0 breast cancer while they were under LA and GA, respectively. The SLN detection rate, a comparison of mapped and harvested SLNs, was compared for both groups. The duration of the SLN biopsies performed under LA was also measured. RESULTS: For both groups a median of 2 SLNs/patient were harvested. The detection rate was 1.00 for the LA group and 0.99 for the GA group. The learning curve for SLN procedures under LA showed a decrease in duration for the consecutive months (not significant). CONCLUSIONS: SLN biopsy can be safely and adequately performed with the patient under LA. It allows early diagnosis of the lymph node status, acquired on an outpatient basis, with minimal discomfort to the patient. The learning curve demonstrated that the LA procedure can quickly be mastered if the surgeon is experienced in performing SLN biopsies.     

Adipocytokines and the metabolic syndrome among older persons with and without obesity: the InCHIANTI study

Objectives Adipose tissue‐derived inflammation may contribute to metabolic alterations and eventually to the metabolic syndrome (MetS). The purpose of this study was to: (1) examine the role of adipocytokines in the association between obesity and the MetS and (2) to determine whether the association is different in obese and non‐obese persons. Design Cross‐sectional population‐based InCHIANTI study. Subjects A total of 944 community‐dwelling adults aged 65 years and older living in Tuscany, Italy. Measurements Obesity was defined as body mass index ≥30 kg/m² and MetS as ≥3 of the ATP‐III criteria. Circulating levels of C‐reactive protein, interleukin (IL)‐6, IL‐1 receptor antagonist (IL‐1ra), IL‐18, tumour necrosis factor (TNF)‐α R1, adiponectin, resistin and leptin were measured. Additionally, insulin resistance was determined using the homeostasis model assessment (HOMA‐IR). Results The prevalence of the MetS was 32%. Both overall and abdominal obesity were significantly associated with the MetS after adjusting for inflammatory cytokines, adipokines and lifestyle factors. After adjusting for multiple confounders and HOMA‐IR, IL‐1ra, TNF‐α R1 and adiponectin (P < 0·05) remained significantly associated with the MetS. Having multiple cytokines in the highest tertile increased the likelihood of having the MetS in both obese (P for trend 0·002) and non‐obese persons (P for trend 0·001) independent of insulin resistance. Conclusions Non‐obese and obese individuals who develop an intense pro‐inflammatory state may be more prone to develop the MetS than those with lower levels of inflammation.