Prediction of post-hepatectomy liver failure by preoperative gadoxetate disodium-enhanced magnetic resonance imaging.

BACKGROUND: Approximately 15% of patients experience post-hepatectomy liver failure after major hepatectomy. Poor hepatocyte uptake of gadoxetate disodium, a magnetic resonance imaging contrast agent, may be a predictor of post-hepatectomy liver failure. METHODS: A retrospective cohort study of patients undergoing major hepatectomy (≥3 segments) with a preoperative gadoxetate disodium-enhanced magnetic resonance imaging was conducted. The liver signal intensity (standardized to the spleen) and the functional liver remnant was calculated to determine if this can predict post-hepatectomy liver failure after major hepatectomy. RESULTS: In 134 patients, low signal intensity of the remnant liver standardized by signal intensity of the spleen in post-contrast images was associated with post-hepatectomy liver failure in multiple logistic regression analysis (Odds Ratio 0.112; 95% CI 0.023-0.551). In a subgroup of 33 patients with lower quartile of functional liver remnant, area under the curve analysis demonstrated a diagnostic accuracy of functional liver remnant to predict post-hepatectomy liver failure of 0.857 with a cut-off value for functional liver remnant of 1.4985 with 80.0% sensitivity and 89.3% specificity. CONCLUSION: Functional liver remnant determined by gadoxetate disodium-enhanced magnetic resonance imaging is a predictor of post-hepatectomy liver failure which may help identify patients for resection, reducing morbidity and mortality.

Bilateral glenohumeral internal rotation deficit (GIRD) in elite gymnasts.

INTRODUCTION: The "Glenohumeral Internal Rotation Deficit (GIRD)" is known as the difference in internal rotation range of motion (IRRM) between the dominant and non-dominant shoulder of overhead athletes as a result of asymmetric loading. As in contrast loading pattern in gymnastics are quite symmetric and structural changes often occur bilaterally, the question arises if GIRD might develop bilaterally in gymnasts as one source of common bilateral shoulder pathologies and to search for underlying structural adaptations. MATERIALS AND METHODS: A group of 35 elite gymnasts (8-24 years) were recruited from a local Olympic Training Centre and compared to a paired cohort of 28 non-overhead athletes. Clinical examinations, digital range of motion (ROM)-measurement, ultrasonographic humeral torsion measurement, and standardized MRI scans of both shoulders were obtained and examined for structural pathologies, cross-sectional areas (CSA) of the rotator cuff muscles and capsular thickness. RESULTS: ROM-measurements showed significant decrease in IRRM in the gymnasts groups by age, with IRRM of 48.6° (SD: 8.4°, CI 95%: 43.0-54.3°) at age group 1 (8-10 years) and IRRM of 10° (SD: 11.4°; CI 95%: 0-22.0°) at age group 4 (18-26 years), that was statistically significant for the entire cohort (p = 0.017) compared to the controls. CSA were not significantly different between the cohorts, while there was a slightly increased humeral retrotorsion in the gymnasts as well as a statistically significant posterior capsular thickening. CONCLUSION: A new bilateral form of GIRD was identified in higher age groups of youth and senior elite gymnasts enrolled in this study. Despite to former definition of GIRD there was no compensatory increase in external rotation range of motion (ERRM) but an association with posterior capsular thickening, while there was no periscapular muscle hypertrophy. Humeral retrotorsion was also slightly increased in the gymnasts group.

Teaching rotary root canal instrumentation using a Peyton teaching approach.

INTRODUCTION: The aim of the study was two evaluate the effectiveness of a Peyton teaching approach for rotary root canal instrumentation, in comparison to the traditional "see one-do one" method. MATERIAL AND METHODS: Forty undergraduate students were randomly divided into two groups (n = 20). Students of the first group (G1) were taught how to use rotary instrumentation using a modified Peyton method, whilst the second group (G2) watched a teaching video (30 min) on the same subject. Both groups instrumented a plastic block and subsequently both mesial canals of an extracted lower molar. The quality of the root canal instrumentation was analysed by 2 blinded observers on video recordings and x-rays. RESULTS: Interobserver correlation was 0.917 (p < .0005; Pearson) for the assessment of the video recordings; students of G1 received significantly more total points (83.55 ± 6.82 points) compared to G2 (69.76 ± 13.82) (p = .001; t-test), the gender had no significant effect on the overall results (p = .444; two-way ANOVA). Significant differences were detected for the categories "initial scouting," "coronal enlargement," "glide path preparation," "preparation using X2 file," "preparation using X3 file" (p < .05; t-test) as well as for the subcategories "sequence of rinse, recapitulation, rinse" (p = .001; t-test) and "recapitulation" (p < .002; t-test). No differences between groups were observed for the radiographic evaluation with respect to working length and canal straightening. CONCLUSION: Teaching rotary instrumentation by using the Peyton approach resulted in improved performance of undergraduate students assessed with a checklist-based process analysis. Enhanced implementation of rotary instrumentation could result in better long-term results of students' root canal treatment.

Perfusion-Dependent Cerebral Autoregulation Impairment in Hemispheric Stroke.

OBJECTIVE: Loss of cerebral autoregulation (CA) plays a key role in secondary neurologic injury. However, the regional distribution of CA impairment after acute cerebral injury remains unclear because, in clinical practice, CA is only assessed within a limited compartment. Here, we performed large-scale regional mapping of cortical perfusion and CA in patients undergoing decompressive surgery for malignant hemispheric stroke. METHODS: In 24 patients, autoregulation over the affected hemisphere was calculated based on direct, 15 to 20-minute cortical perfusion measurement with intraoperative laser speckle imaging and mean arterial blood pressure (MAP) recording. Cortical perfusion was normalized against noninfarcted tissue and 6 perfusion categories from 0% to >100% were defined. The interaction between cortical perfusion and MAP was estimated using a linear random slope model and Pearson correlation. RESULTS: Cortical perfusion and CA impairment were heterogeneously distributed across the entire hemisphere. The degree of CA impairment was significantly greater in areas with critical hypoperfusion (40-60%: 0.42% per mmHg and 60-80%: 0.46% per mmHg) than in noninfarcted (> 100%: 0.22% per mmHg) or infarcted (0-20%: 0.29% per mmHg) areas (*p < 0.001). Pearson correlation confirmed greater CA impairment at critically reduced perfusion (20-40%: r = 0.67; 40-60%: r = 0.68; and 60-80%: r = 0.68) compared to perfusion > 100% (r = 0.36; *p < 0.05). Tissue integrity had no impact on the degree of CA impairment. INTERPRETATION: In hemispheric stroke, CA is impaired across the entire hemisphere to a variable extent. Autoregulation impairment was greatest in hypoperfused and potentially viable tissue, suggesting that precise localization of such regions is essential for effective tailoring of perfusion pressure-based treatment strategies. ANN NEUROL 2021;89:358-368.

Impact of Ventilation Modes on Bronchoscopic Chartis Assessment Outcome in Candidates for Endobronchial Valve Treatment.

BACKGROUND: Endobronchial valve therapy has proven to reduce lung hyperinflation and decrease disease burden in patients with severe lung emphysema. Exclusion of collateral ventilation (CV) of the targeted lobe by using an endobronchial assessment system (Chartis; PulmonX, Drive Redwood City, CA, USA) in combination with software-based fissure integrity analysis (FCS [fissure completeness score]) of computed tomography scans of the lung are established tools to select appropriate patients for endobronchial valve treatment. So far, there is no conclusive evidence if the ventilation mode during bronchoscopy impacts the outcome of Chartis assessments. METHODS: Patients with Chartis assessments and software-based quantification of FCS (StratX; PulmonX, Drive Redwood City, CA, USA) were enrolled in this retrospective study. During bronchoscopy, pulmonary fissure integrity was evaluated with the Chartis assessment system in each patient first under spontaneous breathing and subsequently under high-frequency (HF) jet ventilation. RESULTS: In total, 102 patients were analyzed. Four Chartis phenotypes CV positive (CV+), CV negative (CV-), low flow, and low plateau in spontaneous breathing and HF jet ventilation were identified. The frequency of each Chartis phenotype per lobe was similar in both settings. When comparing Chartis assessments in spontaneous breathing and HF jet ventilation, there was an overall good concordance rate for all analyzed fissures. In agreement, receiver operating characteristic analysis of the FCS showed an almost similar prediction for CV+ and CV- status independent of the ventilation modes. CONCLUSION: Chartis assessment in spontaneous breathing and HF jet ventilation had similar rates in detecting CV in lung emphysema. Our results suggest that both modes are equivalent for the assessment of CV.

The impact of surgical site infection-a cost analysis.

PURPOSE: Surgical site infection (SSI) occurs in up to 25% of patients after elective laparotomy. We aimed to determine the effect of SSI on healthcare costs and patients' quality of life. METHODS: In this post hoc analysis based on the RECIPE trial, we studied a 30-day postoperative outcome of SSI in a single-center, prospective randomized controlled trial comparing subcutaneous wound irrigation with 0.04% polyhexanide to 0.9% saline after elective laparotomy. Total medical costs were analyzed accurately per patient with the tool of our corporate controlling team which is based on diagnosis-related groups in Germany. RESULTS: Between November 2015 and May 2018, 456 patients were recruited. The overall rate of SSI was 28.2%. Overall costs of inpatient treatment were higher in the group with SSI: median 16.685 €; 19.703 USD (IQR 21.638 €; 25.552 USD) vs. median 11.235 €; 13.276 USD (IQR 11.564 €; 13.656 USD); p < 0.001. There was a difference in surgery costs (median 6.664 €; 7.870 USD with SSI vs. median 5.040 €; 5.952 USD without SSI; p = 0.001) and costs on the surgical ward (median 8.404 €; 9.924 USD with SSI vs. median 4.690 €; 5.538 USD without SSI; p < 0.001). Patients with SSI were less satisfied with the cosmetic result (4.3% vs. 16.2%; p < 0.001). Overall costs for patients who were irrigated with saline were median 12.056 €; 14.237 USD vs. median 12.793 €; 15.107 USD in the polyhexanide group (p = 0.52). CONCLUSION: SSI after elective laparotomy increased hospital costs substantially. This is an additional reason why the prevention of SSI is important. Overall costs for intraoperative wound irrigation with saline were comparable with polyhexanide.

Factors influencing the presence of Candida dubliniensis and other non-albicans species in patients with oral lichen planus: a retrospective observational study.

OBJECTIVES: The epidemiologic distribution of non-albicans species in the oral cavity of oral lichen planus (OLP) patients remains uncertain. Therefore, the aim of this study was to identify factors associated with the presence of C. dubliniensis and other non-albicans species. Furthermore, independent risk factors for Candida superinfection in OLP should be identified. MATERIAL AND METHODS: Epidemiologic data and microbiological findings from 268 symptomatic OLP patients who underwent continuous oral swab culture over a 5-year period (2015-2019) were retrospectively reviewed. Candida species identification and semi-quantification were obtained by culture on CHROMagar Candida, followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: C. albicans was the most frequently isolated species (72.3%), followed by C. glabrata (7.3%), C. dubliniensis (5.8%), C. krusei and C. parapsilosis (both 2.6%). The presence of C. dubliniensis was significantly associated with tobacco smoking. Other non-albicans spp. were significantly more often detected in patients using removable dentures. Increasing age and the intake of psychotropic drugs were identified as independent risk factors of Candida superinfection in OLP. CONCLUSION: In OLP patients, certain local and systemic factors increase the risk of carrying potentially drug-resistant Candida species and the development of Candida superinfection of OLP lesions. CLINICAL RELEVANCE: Due to the frequent detection of non-albicans species in OLP, resistance or at least reduced sensitivity to azole antifungals should be expected, especially in smokers and patients using removable dentures. In the case of oral complaints, a superinfection with Candida should be considered, whereby older patients and patients taking psychotropic drugs have an increased risk for oral infection with Candida.

State-level trends in sudden unexpected infant death and immunization in the United States: an ecological study.

BACKGROUND: Sudden unexpected infant death (SUID) continues to be a major contributor to infant mortality in the United States. The objective was to analyze time trends in SUID and their association with immunization coverage. METHODS: The number of deaths and live births per year and per state (1992-2015) was obtained from the Centers for Disease Control and Prevention (CDC). We calculated infant mortality rates (i.e., deaths below one year of age) per 1000 live births for SUID. We obtained data on immunization in children aged 19-35 months with three doses or more of diphtheria-tetanus-pertussis (3+ DTP), polio (3+ Polio), and Haemophilus influenzae type b (3+ Hib) as well as four doses or more of DTP (4+ DTP) from the National Immunization Survey, and data on infant sleep position from the Pregnancy Risk Assessment Monitoring System (PRAMS) Study. Data on poverty and race were derived from the Current Population and American Community Surveys of the U.S. Census Bureau. We calculated mean SUID mortality rates with 95% confidence interval (CI) as well as the annual percentage change using breakpoint analysis. We used Poisson regression with random effects to examine the dependence of SUID rates on immunization coverage, adjusting for sleep position and poverty (1996-2015). In a second model, we additionally adjusted for race (2000-2015). RESULTS: Overall, SUID mortality decreased in the United States. The mean annual percent change was - 9.6 (95% CI = - 10.5, - 8.6) between 1992 and 1996, and - 0.3 (95% CI = - 0.4, - 0.1) from 1996 onwards. The adjusted rate ratios for SUID mortality were 0.91 (95% CI = 0.80, 1.03) per 10% increase for 3+ DTP, 0.88 (95% CI = 0.83, 0.95) for 4+ DTP, 1.00 (95% CI = 0.90, 1.10) for 3+ polio, and 0.95 (95% CI = 0.89, 1.02) for 3+ Hib. After additionally adjusting for race, the rate ratios were 0.76 (95% CI = 0.67, 0.85) for 3+ DTP, 0.83 (95% CI = 0.78, 0.89) for 4+ DTP, 0.81 (95% CI = 0.73, 0.90) for 3+ polio, and 0.94 (95% CI = 0.88, 1.00) for 3+ Hib. CONCLUSIONS: SUID mortality is decreasing, and inversely related to immunization coverage. However, since 1996, the decline has slowed down.

Incidence and survival of HNSCC patients living with HIV compared with HIV-negative HNSCC patients.

PURPOSE: The aim was to analyze the incidence and survival of patients living with HIV (PLWH) with head and neck squamous cell carcinoma (HNSCC) and to compare with a control group of HIV-negative HNSCC patients. METHODS: Clinicopathological data and predictors for overall survival (OS) and disease-free survival (DFS) were investigated (2009-2019). RESULTS: 50 of 5151 HNSCC patients (0.97%) were PLWH, and 76% were smokers. Age ≤ 60 years, HIV-PCR ≤ 50 copies, CD4 cells ≤ 200/mm3, cART treatment, T and UICC classification, oral cavity and nasal/paranasal sinuses, and therapy were significantly associated with OS in univariate analysis. In the multivariate analysis, only age and HIV-PCR independently predicted OS. The OS of the 50 PLWH was not significantly altered compared with the 5101 HIV-negative controls. However, OS and DFS were significantly inferior in advanced tumor stages of PLWH compared with an age-matched control group of 150 HIV-negative patients. CONCLUSIONS: PLWH were diagnosed with HNSCC at a significantly younger age compared to HIV-negative patients. Taking into account patient age at initial diagnosis, both OS and DFS rates in PLWH are significantly worse compared with a matched control group of HIV-negative patients in advanced tumor stages UICC III/IV. The prognosis (OS) is improved when taking cART treatment, the HIV viral load is undetectable and CD4 count is high.

Root canal pre-treatment and adhesive system affect bond strength durability of fiber posts ex vivo.

OBJECTIVES: To investigate the effect of different pre-treatments on the long-term bond strength of fiberglass posts luted either with dual-curing self-etch adhesives and core build-up composites or with a self-adhesive resin (SAR) cement. MATERIALS AND METHODS: In total, 180 human root-filled teeth received post-space preparations and three different dentin pre-treatments (PTs): PT1, ethanol (99%); PT2, ethanol-tertiary-butanol-water-solution (AH Plus Cleaner, Dentsply Sirona; York, USA); and PT3, distilled water (control). Five luting systems were used: FU, Futurabond U (Voco; Cuxhaven, Germany); CL, Clearfil DC Bond (Kuraray Noritake; Okayama, Japan); GR, Gradia Core SE Bond (GC Europe NV; Leuven, Belgium); LU, LuxaBond Universal (DMG; Hamburg, Germany); and RX, RelyX Unicem 2 (3M; Minnesota, USA). Roots were cut into six slices (1 mm thick). From each root canal region, three slices were submitted to immediate and three to post-storage push-out testing. The latter were subjected to thermocycling (5-55°C, 6.000 cycles) and stored for six months in saline solution (0.9%, 37°C). Data were analysed using repeated measures ANOVA and chi-square tests (MV±SD). RESULTS: Bond strength was significantly affected by material (p<0.0005), pre-treatment (p=0.016), and storage (p<0.0005; repeated-measures ANOVA). LU (18.8±8.1MPa) revealed significantly higher bond strength than RX (16.08±6.4MPa), GR (15.1±4.6MPa), CL (13.95±5.2MPa), and FU (13.7±6.3MPa). PT1 (16.5±6.9MPa) revealed significantly higher bond strength than PT3 (14.5±5.7MPa). CONCLUSIONS: A universal adhesive in self-etch mode combined with a core build-up material revealed higher bond strength than a SAR cement, both interacted positively with Ethanol pre-treatment. CLINICAL RELEVANCE STATEMENT: Ethanol (99%) rinsing can be recommended as part of post and core pre-treatment for the investigated luting systems.

Reduction of Postoperative Wound Infections by Antiseptica (RECIPE)?: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether intraoperative subcutaneous wound irrigation with 0.04% polyhexanide can reduce surgical site infection (SSI) in elective laparotomies compared to saline. BACKGROUND: SSI is a common complication after gastrointestinal surgery. To date, there is a lack of evidence whether subcutaneous wound irrigation is beneficial in terms of reduction of SSI. METHODS: The RECIPE trial was an investigator initiated single-center, single-blind prospective, randomized controlled trial with 2 parallel treatment groups, comparing wound irrigation with 0.9% saline to antiseptic 0.04% polyhexanide solution in elective laparotomies. Primary endpoint was the rate of SSI within 30 days postoperatively according to Centers for Disease Control and Prevention criteria. RESULTS: Between February 02, 2015, and May 23, 2018, 456 patients were randomly assigned to saline (n = 228) or polyhexanide (n = 228). Final cohort for analysis comprised 393 patients (202 in the saline and 191 in the polyhexanide group). Overall rate of SSI was 28.2%, n = 111. Simple analysis with cross tabulation revealed that significantly fewer SSIs occurred in the polyhexanide group: n = 70 (34.7%) versus n = 41 (21.5%); P = 0.004. In a multiple logistic regression model the factor wound irrigation with polyhexanide [odds ratio (OR) 0.44; 95% confidence interval (CI) 0.27-0.72; P = 0.001) was associated with risk reduction of SSI. Preoperative anemia (OR 2.08; 95% CI 1.27-3.40; P = 0.004) and more than 5 prior abdominal operations compared to none (OR 8.51; 95% CI 2.57-28.21; P < 0.001) were associated with SSI. CONCLUSIONS: Intraoperative subcutaneous wound irrigation with antiseptic 0.04% polyhexanide solution is effective in reducing SSI after elective laparotomies.

Increasing efficiency of preclinical research by group sequential designs.

Despite the potential benefits of sequential designs, studies evaluating treatments or experimental manipulations in preclinical experimental biomedicine almost exclusively use classical block designs. Our aim with this article is to bring the existing methodology of group sequential designs to the attention of researchers in the preclinical field and to clearly illustrate its potential utility. Group sequential designs can offer higher efficiency than traditional methods and are increasingly used in clinical trials. Using simulation of data, we demonstrate that group sequential designs have the potential to improve the efficiency of experimental studies, even when sample sizes are very small, as is currently prevalent in preclinical experimental biomedicine. When simulating data with a large effect size of d = 1 and a sample size of n = 18 per group, sequential frequentist analysis consumes in the long run only around 80% of the planned number of experimental units. In larger trials (n = 36 per group), additional stopping rules for futility lead to the saving of resources of up to 30% compared to block designs. We argue that these savings should be invested to increase sample sizes and hence power, since the currently underpowered experiments in preclinical biomedicine are a major threat to the value and predictiveness in this research domain.

Implications for post critical illness trial design: sub-phenotyping trajectories of functional recovery among sepsis survivors.

BACKGROUND: Patients who survive critical illness suffer from a significant physical disability. The impact of rehabilitation strategies on health-related quality of life is inconsistent, with population heterogeneity cited as one potential confounder. This secondary analysis aimed to (1) examine trajectories of functional recovery in critically ill patients to delineate sub-phenotypes and (2) to assess differences between these cohorts in both clinical characteristics and clinimetric properties of physical function assessment tools. METHODS: Two hundred ninety-one adult sepsis survivors were followed-up for 24 months by telephone interviews. Physical function was assessed using the Physical Component Score (PCS) of the Short Form-36 Questionnaire (SF-36) and Activities of Daily Living and the Extra Short Musculoskeletal Function Assessment (XSFMA-F/B). Longitudinal trajectories were clustered by factor analysis. Logistical regression analyses were applied to patient characteristics potentially determining cluster allocation. Responsiveness, floor and ceiling effects and concurrent validity were assessed within clusters. RESULTS: One hundred fifty-nine patients completed 24 months of follow-up, presenting overall low PCS scores. Two distinct sub-cohorts were identified, exhibiting complete recovery or persistent impairment. A third sub-cohort could not be classified into either trajectory. Age, education level and number of co-morbidities were independent determinants of poor recovery (AUROC 0.743 ((95%CI 0.659-0.826), p < 0.001). Those with complete recovery trajectories demonstrated high levels of ceiling effects in physical function (PF) (15%), role physical (RP) (45%) and body pain (BP) (57%) domains of the SF-36. Those with persistent impairment demonstrated high levels of floor effects in the same domains: PF (21%), RP (71%) and BP (12%). The PF domain demonstrated high responsiveness between ICU discharge and at 6 months and was predictive of a persistent impairment trajectory (AUROC 0.859 (95%CI 0.804-0.914), p < 0.001). CONCLUSIONS: Within sepsis survivors, two distinct recovery trajectories of physical recovery were demonstrated. Older patients with more co-morbidities and lower educational achievements were more likely to have a persistent physical impairment trajectory. In regard to trajectory prediction, the PF score of the SF-36 was more responsive than the PCS and could be considered for primary outcomes. Future trials should consider adaptive trial designs that can deal with non-responders or sub-cohort specific outcome measures more effectively.

Health-related qualify of life, angina type and coronary artery disease in patients with stable chest pain.

BACKGROUND: Health-related quality of life (HRQoL) is impaired in patients with stable angina but patients often present with other forms of chest pain. The aim of this study was to compare the pre-diagnostic HRQoL in patients with suspected coronary artery disease (CAD) according to angina type, gender, and presence of obstructive CAD. METHODS: From the pilot study for the European DISCHARGE trial, we analysed data from 24 sites including 1263 patients (45.9% women, 61.1 ± 11.3 years) who were clinically referred for invasive coronary angiography (ICA; 617 patients) or coronary computed tomography angiography (CTA; 646 patients). Prior to the procedures, patients completed HRQoL questionnaires: the Short Form (SF)-12v2, the EuroQoL (EQ-5D-3 L) and the Hospital Anxiety and Depression Scale. RESULTS: Fifty-five percent of ICA and 35% of CTA patients had typical angina, 23 and 33% had atypical angina, 18 and 28% had non-anginal chest discomfort and 5 and 5% had other chest discomfort, respectively. Patients with typical angina had the poorest physical functioning compared to the other angina groups (SF-12 physical component score; 41.2 ± 8.8, 43.3 ± 9.1, 46.2 ± 9.0, 46.4 ± 11.4, respectively, all age and gender-adjusted p < 0.01), and highest anxiety levels (8.3 ± 4.1, 7.5 ± 4.1, 6.5 ± 4.0, 4.7 ± 4.5, respectively, all adjusted p < 0.01). On all other measures, patients with typical or atypical angina had lower HRQoL compared to the two other groups (all adjusted p < 0.05). HRQoL did not differ between patients with and without obstructive CAD while women had worse HRQoL compared with men, irrespective of age and angina type. CONCLUSIONS: Prior to a diagnostic procedure for stable chest pain, HRQoL is associated with chest pain characteristics, but not with obstructive CAD, and is significantly lower in women. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02400229.

Correction to: Health-related qualify of life, angina type and coronary artery disease in patients with stable chest pain.

An amendment to this paper has been published and can be accessed via the original article.

International time trends in sudden unexpected infant death, 1969-2012.

BACKGROUND: Sudden unexpected infant death (SUID) - including sudden infant death syndrome (SIDS) - continues to be a major contributor to infant mortality worldwide. Our objective was to analyse time trends and to identify country-clusters. METHODS: The National Statistical Offices of 52 countries provided the number of deaths and live births (1969-2012). We calculated infant mortality rates per 1000 live births for SUID, SIDS, and all-cause mortality. Overall, 29 countries provided sufficient data for time course analyses of SUID. To sensitively model change over time, we smoothed the curves of mortality rates (1980-2010). We performed a hierarchical cluster analysis to identify clusters of time trends for SUID and SIDS, including all-cause infant mortality. RESULTS: All-cause infant mortality declined from 28.5 to 4.8 per 1000 live births (mean 12.4; 95% confidence interval 12.0-12.9) between 1969 and 2012. The cluster analysis revealed four country-clusters. Clusters 1 and 2 mostly contained countries showing the typical peak of SUID mortality during the 1980s. Cluster 1 had higher SUID mortality compared to cluster 2. All-cause infant mortality was low in both clusters but higher in cluster 1 compared to cluster 2. Clusters 3 and 4 had low rates of SUID without a peak during the 1980s. Cluster 3 had the highest all-cause infant mortality of all clusters. Cluster 4 had an intermediate all-cause infant mortality. The time trends of SUID and SIDS mortality were similar. CONCLUSIONS: The country-specific time trends in SUID varied considerably. The identification of country-clusters may promote research into how changes in sleep position, smoking, immunisation, or other factors are related to our findings.

Tumor budding outperforms ypT and ypN classification in predicting outcome of rectal cancer after neoadjuvant chemoradiotherapy.

BACKGROUND: Budding is a complementary prognostic factor for colorectal cancer. In this study, we aimed to clarify the role of tumor budding in rectal cancer patients after preoperative chemoradiotherapy. METHODS: A total of 124 patients with rectal cancer treated with neoadjuvant chemoradiotherapy and consecutive surgery were included. Surgical specimens were evaluated for budding and routine clinicopathological features. Budding was evaluated on hematoxylin and eosin (H&E)-stained slides and by cytokeratin immunohistochemical (IHC) staining. RESULTS: A budding rate of 36.9% (n = 38) by H&E and 55.6% (n = 55) by IHC was observed. Budding was significantly associated with a high ypT and ypN status, poor differentiation, and low degrees of tumor regression. Moreover, budding was strongly predictive of a worse patient outcome, as measured by tumor recurrence or death. In multivariate analyses, budding remained the only significant parameter for overall survival and was even superior to the ypT and ypN status (budding in H&E: hazard ratio (HR) 2.72, 95% confidence interval (95% CI) 1.15-6.44, p = 0.023; budding in IHC: HR 5.19, 95% CI 1.62-16.61, p = 0.006). CONCLUSION: Budding is a strong prognostic predictor of survival in rectal cancer patients after neoadjuvant therapy. A standardized evaluation of tumor budding after neoadjuvant therapy may thus aid in risk stratification and guide the clinical management of patients with rectal cancer. Immunostaining can help to enhance the diagnostic accuracy and prognostic significance.

Following in the footsteps of Hippocrates-interrelation between the incidence of odontogenic abscess and meteorological parameters.

OBJECTIVES: Although many physicians in daily practice assume a connection between odontogenic infections and meteorological parameters, this has not yet been scientifically proven. Therefore, the aim of the present study was to evaluate the incidence of odontogenic abscess (OA) in relation to outdoor temperature and atmospheric pressure. PATIENTS AND METHODS: An analysis of patients with an odontogenic abscess who presented at the emergency department within a period of 24 months was performed. Only patients who had not received surgical or antibiotic treatment prior to presentation and who lived in Berlin/Brandenburg were included. The OA incidence was correlated with the mean/maximum outdoor temperature and atmospheric pressure starting from 14 days before presentation. The statistical analysis was carried out using Poisson regression models with OA incidence as dependent and meteorological parameters as independent variables. RESULTS: A total of 535 patients (mean age 39.4 years; range 1 to 95 years) with 538 cases were included. Of these, 227 were hospitalized. The most frequent diagnosis was a canine fossa abscess. A significant association between mean (p = 0.0153) and maximum temperature (p = 0.008) on the day of the presentation and abscess incidence was observed. Furthermore, a significant correlation between OA incidence and maximum temperature 2 days before presentation was found (p = 0.034). The deviation of the mean temperature on the day of the presentation from the monthly mean temperature had a significant influence (p = 0.021) on the incidence of OA. In contrast to temperature, atmospheric pressure had no significant influence on the incidence of OA. CONCLUSION: This study supports a relationship between the incidence of odontogenic abscess and outdoor temperature, but not atmospheric pressure. A significantly higher frequency of patients with an OA presented at our emergency department on days with (comparably) low and high outdoor temperatures. Furthermore, a significant correlation between incidence and maximum temperature 2 days before presentation was found. CLINICAL RELEVANCE: The treatment of odontogenic infections has become a significant economic burden to public health care facilities. The results of this study may help to adapt the numbers of doctors/dentists on duty in relation to different weather conditions. In any case, it is an impetus to think outside the box.

Salvage radiotherapy in prostate cancer patients with biochemical relapse after radical prostatectomy : Prolongation of prostate-specific antigen doubling time in patients with subsequent biochemical progression.

BACKGROUND: In patients with prostate cancer (PCa) and biochemical progression (BP) after radical prostatectomy (RP), salvage radiotherapy (sRT) improves prostate cancer-specific survival (PCSS), but this evidence is based only on retrospective data. PATIENTS AND METHODS: In addition to our previous study of 151 patients with PCa and BP after RP, we performed univariate analyses of prostate-specific antigen (PSA) kinetics during sRT. In 11 patients with BP or initiation of hormonal treatment (HT) within 180 days after sRT, risk factors were assessed using Mann-Whitney U tests. PSA doubling times (PSADT) before and after sRT in 82 patients with BP after sRT were compared by a Wilcoxon test. RESULTS: After a median follow-up of 82 months, analysis of PSA kinetics during sRT did not show a statistically significant impact on a subsequent BP, PCSS, or overall survival at an administered dose of 30 or 45 Gy. The subgroup analysis of patients with early BP or early HT revealed higher Gleason scores (p = 0.008) and preoperative PSA values (p = 0.005), shorter PSADT prior to sRT (p < 0.0005), and longer time intervals from RP until the start of sRT (p = 0.005) compared to all other patients. In patients with subsequent BP, PSADTs were significantly prolonged after sRT (median PSADT 4.5 months before and 9.9 months after sRT, p < 0.0005). CONCLUSION: PSA monitoring during sRT did not predict the therapeutic success. Subgroup analysis suggests a lower probability of benefit for patients with the abovenamed risk factors . However, the prolonged PSADT after sRT reflects a benefit of sRT for the vast majority of patients.

Phase II trial to investigate the safety and efficacy of orally applied niclosamide in patients with metachronous or sychronous metastases of a colorectal cancer progressing after therapy: the NIKOLO trial.

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of all cancer deaths in Europe and the Western world with a lifetime risk of approximately 5%. Despite several improvements in the treatment of patients with unresectable CRC prognosis is poor and there is the need of developing new treatment strategies for patients with metastatic chemorefractory disease. The S100 calcium binding protein A4 (S100A4) predicts metastasis formation and reduced CRC patient survival. S100A4 was previously identified as transcriptional target of the Wnt/ß-catenin signaling pathway. The Food and Drug Administration (FDA)-approved anti-helminthic drug niclosamide is known to intervene in the Wnt/ß-catenin pathway signaling, leading to reduced expression of S100A4 linked to restricted in vivo metastasis formation. Thus, we aim at translation of our findings on restricting S100A4-driven metastasis into clinical practice for treating metastasized CRC patients progressing after standard therapy. METHODS/DESIGN: NIKOLO is a phase II, single center, one-arm open-label clinical trial to investigate the safety and efficacy of niclosamide tablets in patients with metastasized CRC progressing under standard therapy. Eligible patients will receive 2 g of orally applied niclosamide once a day and will continue with the treatment once daily till disease progression or toxicity. Toxicities will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03. The primary objective of this trial is to assess the progression free survival after 4 months, secondary objectives are overall survival, time to progression, disease control rate (remission + partial remission + stable disease), and safety. Furthermore, pharmacokinetic analysis will be conducted to evaluate niclosamide plasma concentration. DISCUSSION: This study is expected to provide evidence of the feasibility, toxicity and efficacy of niclosamide in the treatment of patients with metastasized CRC and could help to establish a new treatment option. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (NCT02519582) and the European Clinical Trials Database (EudraCT 2014-005151-20).