A Log Ratio-Based Analysis of Individual Changes in the Composition of the Oral Microbiota in Different Dietary Phases

Background: Investigating the influence of nutrition on oral health has a long scientific history. Due to recent technical advances like sequencing techniques for the oral microbiota, this topic has gained scientific interest again. A basic challenge is to understand the influence of nutrition on the oral microbiota and on the interaction between the oral bacteria, which is also statistically challenging. Methods: Log-transformed ratios of two bacteria concentrations are introduced as the basic analytic tool. The framework is illustrated by application in an experimental study exposing eleven participants to different nutrition schemes in five consecutive phases. Results: The method could be sufficiently used to analyse the interrelation between the bacteria and to identify some bacterial groups with the same as well as different reactions to additional dietary components. It was found that the strongest changes in bacterial concentrations were achieved by the additional consumption of dairy products. Conclusion: A log ratio-based analysis offers insights into the relation of different bacteria while taking specific features of compositional data into account. The presented methods allow becoming independent of the behaviour of other bacteria, which is a disadvantage of common analysis methods of compositions. The results indicate that modulations of the oral biofilm microbiota due to nutrition change can be attained.     

Four Additional Questions for the Preparation Hypothesis

Archives of Sexual Behavior -     

Surgery of labio-maxillo-palatal clefts during humanitarian mission in the Philippines

After describing the Philippines and the Comité de Soutien Enfance Philippines, a humanitarian association with a three-fold objective: to build, to educate and to treat, the authors present the organization and practical conduct of their missions abroad which have enabled them to treat almost 400 patients with cleft lip and palate between the ages of 3 months and 46 years.     

A nationwide cohort study on Creutzfeldt-Jakob disease among human growth hormone recipients

OBJECTIVE: In 1991, a Dutch patient who had been treated from 1963 to 1969 with human-derived growth hormone died of Creutzfeldt-Jakob disease (CJD). This study was performed to investigate whether among other Dutch human growth hormone recipients there were clinically suspected cases of iatrogenic CJD. METHODS: In a retrospective cohort study, all patients (n = 564) treated with human-derived growth hormone before May 1985 and recorded in the Dutch National Growth Registry were followed up until January 1995 for a clinical diagnosis of CJD. For this purpose, all human growth hormone recipients were linked to a database of the Foundation for Health Care Information comprising hospital discharges with a clinical diagnosis of iatrogenic CJD. Linkage of the two databases was performed on the basis of date of birth and gender. Subsequently, verification of patient's name and initials of the positively matched pairs took place. RESULTS: Linkage provided 37 positively matched pairs concerning 29 individual patients. After verification, no name from the hospital discharge records corresponded to the names of the human growth hormone recipients. CONCLUSIONS The follow-up of 564 Dutch human growth hormone recipients, who had been treated with human growth hormone until 1985 did not establish any clinically suspected case of iatrogenic CJD. Future cases, however, can still emerge due to the potentially long incubation period of prion diseases.     

High Gleason grade carcinoma at a positive surgical margin predicts biochemical failure after radical prostatectomy and may guide adjuvant radiotherapy

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Only 30–35% of patients with positive surgical margins after radical prostatectomy develop recurrent disease. Adjuvant radiotherapy reduces the rate of biochemical relapse or metastasis and improves overall survival after radical prostatectomy. Various pathological factors, such as location and extent of positive margins, have been proposed as possible prognostic factors in men with margin‐positive prostate cancer, however, the recent International Society of Urological Pathology consensus meeting in Boston noted that there is limited data on the significance of Gleason grade of the carcinoma at a positive margin. The present study shows that the presence of high grade prostate cancer, i.e. Gleason pattern 4 or 5, at a positive surgical margin is an independent predictor of biochemical recurrence after radical prostatectomy. Moreover, patients with lower grade carcinoma at the margin have a similar prognosis to men with negative margins. Hence, assessment of Gleason grade at the site of positive margin may aid optimal selection of patients for adjuvant radiotherapy.

OBJECTIVE

• ? To establish predictors of biochemical recurrence by analysing the pathological characteristics of positive surgical margins (PSMs), including Gleason grade of the carcinoma at the involved margin.

PATIENTS AND METHODS

• ? Clinicopathological and outcome data on 940 patients who underwent radical prostatectomy (RP) between 1997 and 2003 were collected.
• ? Of these, 285 (30.3%) patients with PSMs were identified for pathological review, including assessment of location of margin, linear extent, number of PSMs, plane of margin and Gleason grade (3 vs 4 or 5) at the margin.

RESULTS

• ? At a median follow‐up of 82 months, the biochemical recurrence rate of the PSM cohort was 29%.
• ? On univariate analysis, the presence of Gleason grade 4 or 5 at the margin (34.4% of cases) was significantly associated with biochemical recurrence (hazard ratio [HR] 2.80, 95% confidence interval [CI]= 1.82–4.32, P < 0.001) compared with the presence of Gleason grade 3.
• ? Linear extent of margin involvement was also associated with recurrence (P= 0.009).
• ? Single vs multiple margin involvement, location, and plane of the involved margin were not significant predictors of recurrence.
• ? On multivariate analysis, Gleason grade 4 or 5 at the margin remained an independent predictor of recurrence (HR 2.14, 95% CI = 1.29–4.03, P= 0.003).

CONCLUSION

• ? The Gleason grade at the site of a PSM identifies patients at increased risk of biochemical recurrence and should aid stratification of patients for adjuvant radiation therapy.

     

A methylation assay for the detection of non-muscle-invasive bladder cancer (NMIBC) recurrences in voided urine

What's known on the subject? and What does the study add? Multiple studies report on the detection of methylation in voided urine samples as a possible approach for the follow‐up of non‐muscle invasive bladder cancer patients. Previous studies analyze methylation gene panels in a mixture of primary and recurrent tumours. As primary tumours are larger than recurrent tumours and thus easier to detect in urine, validation of methylation markers in urine samples from patients with primary tumours will result in a test sensitivity that does not reflect the true sensitivity of the assay. This study is the first to select a subset of genes specifically methylated in non‐muscle invasive bladder cancer recurrences and validates the gene panel in two independent sets of urine samples from recurrent patients, thus simulating the disease course according to the clinical presentation.

OBJECTIVE

• ? To develop a methylation‐specific multiplex ligation‐dependent probe amplification (MS‐MLPA) assay for the detection of non‐muscle invasive bladder cancer (NMIBC) recurrences in voided urine.

PATIENTS AND METHODS

• ? Genes frequently methylated in NMIBC tumours (n= 37) were selected to develop a BC‐specific MS‐MLPA assay.
• ? Genes methylated in blood from patientswith BC (n= 29) and genes methylated in urine from patients with no history of BC (n= 46) were excluded.
• ? A four‐gene panel with the highest predictive value was selected from the initial assay. This four‐gene panel was tested and validated on urine from patients with a histologically confirmed recurrence (n= 68 test set; n= 49 validation set) and urine samples from patients without BC (n= 91, test set) and urine from recurrence‐free BC (rec‐free BC) patients (n= 60, validation set).
• ? A model was developed to predict the probability of having a recurrence based on methylation of the four‐gene panel and a threshold probability with the highest sensitivity and specificity was determined.
• ? The outcome of the model was validated on BC urine samples (n= 65) and on urine samples from rec‐free BC patients (n= 29).

RESULTS

• ? The BC MS‐MLPA assay consisted of 23 methylation probes. The selected four‐gene panel included: APC_a, TERT_a, TERT_b, and EDNRB. This panel reached an area under the receiver operating characteristic curve (AUC) of 0.82 (test set) and AUC 0.69 (validation set). Sensitivity and specificity for the detection of a concomitant tumour were 63.3% and 58.3% respectively (test set) and 72.3% and 55.2%, respectively (validation set).

CONCLUSIONS

• ? We have developed a methylation detection assay specifically for the detection of recurrences in patients with NMIBC in voided urine.
• ? The findings are promising and improvement of this test could eventually contribute to a more individualized patient friendly surveillance.

     

Does ICU length of stay influence quality of life?

BACKGROUND: Patients with prolonged stay in the intensive care unit (ICU) use a disproportionate share of resources. However, it is not known if such treatment results in impaired quality of life (QOL) as compared to patients with a short length of stay (LOS) when taking into account the initial severity of illness. METHODS: Prospective, observational case-control study in a university hospital surgical and trauma adult ICU. All patients admitted to the ICU during a 1-year period were included. Patients with a cumulative LOS in the ICU > 7 days, surviving up to 1 year after ICU admission and consenting were identified (group L, n = 75) and matched to individuals with a shorter stay (group S). Matching criteria were diagnostic group and severity of illness. Health-related quality of life (HRQOL) was assessed 1 year after admission using the short-form 36 (SF-36) and was compared between groups and to the general population. Further, overall QOL was estimated using a visual analogue scale (VAS) and willingness to consent to future intensive care, and was compared between groups L and S. RESULTS: Based on ANCOVA, a significant difference between groups L and S was noted for two out of eight scales: role physical (P = 0.033) and vitality (P = 0.041). No differences were found for the physical component summary (P = 0.065), the mental component summary (P = 0.267) or the VAS (P = 0.316). Further, there was no difference in expectation to consent to future intensive care (P = 0.149). As compared to the general population, we found similar scores for the mental component summary and for three of eight scales in group L and five of eight scales in group S. CONCLUSIONS: When taking into account severity of illness, HRQOL 1 year after intensive care is comparable between patients with a short and a long LOS in the ICU. Thus, prolonged stay in the ICU per se must not be taken as an indicator of future poorer HRQOL. However, as compared to the general population, significant differences, mostly in physical aspects of QOL, were found for both groups of patients.     

Low incidence of acute urinary retention in the general male population: the triumph project

OBJECTIVE: To describe the incidence of acute urinary retention (AUR) in the general male population and in a population of men newly diagnosed with lower urinary tract symptoms suggestive of BPH (LUTS/BPH). METHODS: We performed a retrospective cohort study in the Integrated Primary Care Information (IPCI) database, a GP research database in The Netherlands, during the period 1995-2000. All males, > or =45 years, without a history of AUR or radical cystectomy were included in the study. In addition, we followed a sub-cohort of men, newly diagnosed with LUTS/BPH. AUR was defined as the sudden inability to urinate, requiring catheterization. RESULTS: Amongst 56,958 males with a mean follow-up of 2.8 years, 344 AUR cases occurred (incidence rate 2.2/1000 man-years) of whom more than 40% were precipitated. AUR was the first symptom of LUTS/BPH in 73 (49%) of the 149 AUR cases that occurred in men newly diagnosed with LUTS/BPH. The risk of AUR was 11-fold higher in patients newly diagnosed with LUTS/BPH (RR 11.5; 95%CI: 8.4-15.6) with an overall incidence rate of 18.3/1000 man-years (95%CI: 14.5-22.8). CONCLUSIONS: The incidence rate of AUR is low in the general population but substantial in a population of men newly diagnosed with LUTS/BPH. The incidence rate increases with age and AUR is precipitated in approximately 40% of all cases. Within the LUTS/BPH cohort, AUR is the first presenting symptom of BPH in 50% of all AUR cases.