Yokenella regensburgei-Past, Present and Future.

Yokenella regensburgei is a Gram-negative rod part of the Enterobacteriaceae family (order Enterobacterales) and a rare cause of human infections. Although improved diagnostic methods have led to an increase in reports of this elusive pathogen, information remains limited. In order to provide a better understanding of this bacterium, we developed the first comprehensive review of its biology, biochemical profile, antimicrobial resistance pattern, virulence factors, natural reservoir and involvement in various veterinary and human infections. Human infections with this bacterium are scarcely reported, most probably due to constraints regarding its identification and biochemical similarities to Hafnia alvei. Multiple systematic searches revealed 23 cases of human infection, with a seemingly worldwide distribution, mostly in middle-aged or elderly male patients, often associated with immunosuppression. To date, Y. regensburgei has been reported in skin and soft tissue infections, bacteremia and sepsis, osteoarticular infections and in others such as urinary tract and digestive infections. The unique ability of Y. regensburgei to degrade polystyrene presents a novel and promising avenue for addressing plastic pollution in the near future. However, large-scale applications of this bacterium will undoubtedly increase human exposure, highlighting the necessity for comprehensive research into its role in human and veterinary infections, pathogenicity and antibiotic resistance.

Intrapartum Quality of Care among Healthy Women: A Population-Based Cohort Study in an Italian Region.

Although the quality of care during childbirth is a maternity service's goal, less is known about the impact of the birth setting dimension on provision of care, defined as evidence-based intrapartum midwifery practices. This study's aim was to investigate the impact of hospital birth volume (≥1000 vs. <1000 births/year) on intrapartum midwifery care and perinatal outcomes. We conducted a population-based cohort study on healthy pregnant women who gave birth between 2018 and 2022 in Lombardy, Italy. A total of 145,224 (41.14%) women were selected from nationally linked databases. To achieve the primary aim, log-binomial regression models were constructed. More than 70% of healthy pregnant women gave birth in hospitals (≥1000 births/year) where there was lower use of nonpharmacological coping strategies, higher likelihood of epidural analgesia, episiotomy, birth companion's presence at birth, skin-to-skin contact, and first breastfeeding within 1 h (p-value < 0.001). Midwives attended almost all the births regardless of birth volume (98.80%), while gynecologists and pediatricians were more frequently present in smaller hospitals. There were no significant differences in perinatal outcomes. Our findings highlighted the impact of the birth setting dimension on the provision of care to healthy pregnant women.

International consensus on the management of metastatic gastric cancer: step by step in the foggy landscape : Bertinoro Workshop, November 2022.

BACKGROUND: Many gastric cancer patients in Western countries are diagnosed as metastatic with a median overall survival of less than twelve months using standard chemotherapy. Innovative treatments, like targeted therapy or immunotherapy, have recently proved to ameliorate prognosis, but a general agreement on managing oligometastatic disease has yet to be achieved. An international multi-disciplinary workshop was held in Bertinoro, Italy, in November 2022 to verify whether achieving a consensus on at least some topics was possible. METHODS: A two-round Delphi process was carried out, where participants were asked to answer 32 multiple-choice questions about CT, laparoscopic staging and biomarkers, systemic treatment for different localization, role and indication of palliative care. Consensus was established with at least a 67% agreement. RESULTS: The assembly agreed to define oligometastases as a "dynamic" disease which either regresses or remains stable in response to systemic treatment. In addition, the definition of oligometastases was restricted to the following sites: para-aortic nodal stations, liver, lung, and peritoneum, excluding bones. In detail, the following conditions should be considered as oligometastases: involvement of para-aortic stations, in particular 16a2 or 16b1; up to three technically resectable liver metastases; three unilateral or two bilateral lung metastases; peritoneal carcinomatosis with PCI ≤ 6. No consensus was achieved on how to classify positive cytology, which was considered as oligometastatic by 55% of participants only if converted to negative after chemotherapy. CONCLUSION: As assessed at the time of diagnosis, surgical treatment of oligometastases should aim at R0 curativity on the entire disease volume, including both the primary tumor and its metastases. Conversion surgery was defined as surgery on the residual volume of disease, which was initially not resectable for technical and/or oncological reasons but nevertheless responded to first-line treatment.

Treatment response of advanced HNSCC towards immune checkpoint inhibition is associated with an activated effector memory T cell phenotype.

Locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with a poor prognosis. The introduction of PD-1 inhibitors has led to a significant improvement in survival, but only a subpopulation of patients responds to therapy. Current biomarkers cannot reliably identify these patients. The identification of biomarkers for the prediction and monitoring of immunotherapy is therefore of great importance. In this study, we characterized lymphocyte subsets in the peripheral blood of HNSCC patients under PD-1 inhibition. Patients with primary response (n=11) to PD-1 inhibition showed an increase of the CD3+ effector memory (CD3/EM) population and an elevated expression of the activation marker CD69 in CD3+ T cells, particularly in the CD3/EM subpopulation at 3 months when treatment response was assessed. In contrast, patients with primary treatment failure and progressive disease (n=9) despite PD-1 inhibition had lower absolute lymphocyte counts and an increased expression of CTLA-4 in CD3+ T cells at the time of treatment failure compared with baseline, particularly in CD4+ and CD8+ effector memory populations. Our results demonstrate that HNSCC patients' response to immune checkpoint inhibition shows a distinct immune signature in peripheral blood, which could help identify refractory patients earlier. Furthermore, strategies to overcome primary therapy failure by inducing a beneficial T cell phenotype or adding alternative immune checkpoint inhibitors could improve response rates and survival of HNSCC patients.

Influence of the Transmucosal Surface of Dental Implants on the Soft Tissue Attachment Level and Marginal Bone Loss in Preclinical Studies: A Systematic Review.

PURPOSE: To determine the characteristics of dental implant transmucosal surfaces that influence soft tissue attachment and marginal bone loss (MBL). MATERIALS AND METHODS: The PubMed, Embase, and Cochrane Library electronic databases were searched based on predefined PICO eligibility criteria. Data from animal studies that compared junctional epithelium and connective tissue attachment and MBL from 4 days to 72 weeks were analyzed. The risk of bias was performed with the Systematic Review Centre for Laboratory Animal Experimentation tool. A rank analysis evaluation of data was performed, and the most frequently appearing materials/surfaces for each tissue compartment were identified. RESULTS: The search identified 3,549 studies, 28 of which were eligible for analysis, with an average risk of bias of 28% ± 10%. Machined, polished, etched, sandblasted, or coated titanium and zirconia materials/surfaces were most frequently examined. Several studies investigated lithium disilicate, polyether ether ketone (PEEK) or polyether ketone ketone (PEKK), aluminum oxide, and gold. Based on ranking and frequency of use at different time points, titanium grade IV (Ti-4) microthreads with a polished neck area most frequently supported natural tooth-like junctional epithelial attachment (≤ 1.5 mm), while machined Ti-4 and machined titanium grade V (Ti-5) most frequently supported connective tissue attachment (≤ 1.25 mm) and led to the least MBL (≤ 0.75 mm). CONCLUSIONS: Analyzed data suggest that Ti-4 microthreads with a polished neck area and machined Ti-4 and Ti-5 were the materials/surfaces of choice for the transmucosal part of implants. However, the extensive heterogeneity in reported studies precludes solid identification of the best materials/surfaces.

TOFIMS mass spectrometry-based immunopeptidomics refines tumor antigen identification.

T cell recognition of human leukocyte antigen (HLA)-presented tumor-associated peptides is central for cancer immune surveillance. Mass spectrometry (MS)-based immunopeptidomics represents the only unbiased method for the direct identification and characterization of naturally presented tumor-associated peptides, a key prerequisite for the development of T cell-based immunotherapies. This study reports on the implementation of ion mobility separation-based time-of-flight (TOFIMS) MS for next-generation immunopeptidomics, enabling high-speed and sensitive detection of HLA-presented peptides. Applying TOFIMS-based immunopeptidomics, a novel extensive benignTOFIMS dataset was generated from 94 primary benign samples of solid tissue and hematological origin, which enabled the expansion of benign reference immunopeptidome databases with > 150,000 HLA-presented peptides, the refinement of previously described tumor antigens, as well as the identification of frequently presented self antigens and not yet described tumor antigens comprising low abundant mutation-derived neoepitopes that might serve as targets for future cancer immunotherapy development.

Risk factors for post-acute sequelae of COVID-19: Survey results from a tertiary care hospital.

Identifying risk factors for post-acute sequelae of COVID-19 (PASC) is important. We conducted a multicenter cross-sectional survey study to define and characterize risk factors for severe COVID-19 in adults (≥18 years) treated at our virtual COVID-19 clinic from March 1, 2020, through March 31, 2021. We assessed patient demographics, symptom types, and persistence, incidence of PASC, and COVID-19-caused hospitalizations. Surveyed patients were also asked to rate their perception of the severity of their acute COVID-19 symptoms. Continuous variables were summarized descriptively. Differences among groups categorized by acute COVID-19 symptom severity level (mild/very mild, moderate, and severe/very severe) were evaluated with the Kruskal-Wallis rank sum test for continuous measures and the Pearson χ2 test for categorical measures. A total of 3094 adults completed the survey. More respondents with severe/very severe acute COVID-19 symptoms reported having PASC than did those with mild/very mild and moderate acute symptoms. A significantly greater proportion of respondents with PASC were women (68.4% vs 56.7%, p < 0.001), had been hospitalized (12.2% vs 4.4%, p < 0.001), reported having negative psychological COVID-19-related repercussions (39.9% vs 15.3%, p < 0.001), and required more than 1 month to resume normal activities (38.8% vs 12.9%, p < 0.001) than did those without PASC. These findings may improve our understanding of PASC and provide a framework for early recognition of and intervention for patients at higher risk for PASC. Further research is needed to understand the predictors of persistent symptoms after acute SARS-CoV-2 infection and the risk of PASC.

Clinical differences in symptomology, characteristics, and risk factors in patients with post-acute sequelae of COVID-19: an experience from a tertiary-care academic center.

Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus SARS-CoV-2 and has caused significant mortality and morbidity since it was first recognized in Wuhan, China in December 2019. Patients may suffer from a constellation of symptoms termed post-acute sequelae of COVID-19 (PASC) . Here we present findings of a retrospective cohort study describing the prevalence and predicting factors of patient-reported post-acute sequelae of COVID-19 (PASC). Categorical variables were summarized as frequency (percentage) and compared between vaccine status groups using Fisher's exact test. Continuous variables were reported as median (range) and compared between the groups using Kruskal-Wallis test. All tests were two-sided with p value <0.05 considered statistically significant. Survey data from 132 patients with a median age of 45 years, 68% female, 83% Caucasian/Non-Hispanic. The most frequently reported PASC symptoms include fatigue (84.8%), dyspnea (54.5%), cognitive dysfunction (53%), myalgias (37.1%), lightheadedness or vertigo (36.4%), chest pain (34.8%), palpitations (34.8%), headaches (34.1%), arthralgias (31.8%), and unrefreshing sleep (31.1%). There is mounting evidence that supports higher prevalence of PASC in women, White/Caucasian, and middle-aged individuals. This knowledge can provide guidance to clinical practices to anticipate and support healthcare and self-care needs for patients at higher risk to developing PASC.

Circadian Rhythm and Risk of Hemorrhagic Transformation after Acute Ischemic Stroke Treated with Intravenous Thrombolysis - A Systematic Review.

BACKGROUND: A circadian pattern for the onset of acute ischemic stroke (AIS) has been described, with a higher risk in the early morning and a lower risk during nighttime. However, data assessing the circadian distribution of hemorrhagic transformation after intravenous thrombolysis (ivT) are still incongruent. OBJECTIVES: This review aimed to evaluate whether the time interval based on AIS onset or ivT time could influence the occurrence of intracranial hemorrhage (ICH) related to ivT and if the circadian rhythm of endogenous production of tissue plasminogen activator (t-PA) favors ICH occurrence. METHODS: We conducted a systematic review following the PRISMA guidelines, searching PubMed and Embase for articles in English using the keywords: 'stroke', 'thrombolysis', and 'circadian'. Articles investigating the AIS onset or ivT time effects on circadian variations of ICH in AIS adult patients treated with ivT were included. Based on ICH's incidence and odds ratio, time intervals associated with higher risk and time intervals associated with lower risk were defined. The Newcastle-Ottawa Scale was used to assess the risk of bias. The resulting data were reported in a qualitative narrative synthesis. RESULTS: From the 70 abstracts returned by electronic literature search, six studies with 33,365 patients fulfilled the inclusion criteria, out of which three were retrospective analysis studies, one case-control study, one prospective study, and one post hoc analysis of a multicentre trial. Some studies assessed the relationship between ICH occurrence and circadian rhythm depending on AIS onset time (n = 2), treatment time (n = 2), or both (n = 4). All studies investigated the patients' comorbidities as confounding variables for the circadian pattern of symptomatic ICH (sICH). Two studies found no association between AIS onset or ivT time and patient risk factors, but the other four found several differences and used multivariate logistic regression models to balance these covariates. The overall score of the Newcastle- Ottawa scale was 83.3%, which might be interpreted as overall high quality. CONCLUSION: ICH occurred after ivT seems to follow a circadian pattern; the 18:00-00:00 time frame was the safest one, and patients with AIS onset or ivT time between these hours had the lowest incidence of any ICH, including sICH. The 06:00-12:00 block was associated with the highest incidence of ICH and sICH. However, the analysis is limited by the small number of included studies and the heterogeneous findings reported. Further homogenized studies using comparable time frames and sICH definitions are needed to demonstrate this circadian pattern. The review protocol was registered in the OSF database under reference UHNF, doi:10.17605/OSF.IO/UHNF6.

The Burden of Cerebral Venous Thrombosis in a Romanian Population across a 5-Year Period.

Health policies in transitioning health systems are rarely informed by the social burden and the incidence shifts in disease epidemiology. Cerebral venous thrombosis (CVT) is a type of stroke more often affecting younger adults and women, with higher incidences being reported in recent studies. A retrospective, hospital-based population study was conducted at Cluj-Napoca Emergency County Hospital across a 5-year period between 2017 and 2021. The overall incidence and the rates in distinctive gender and age groups were assessed. Length of hospital stay (LHS), modified Rankin score (mRS) and mortality at discharge and at 3 months were calculated. Fifty-three patients were included. The median age was 45 years, and 64.2% were women. In our population of 3,043,998 person-years, 53 CVT cases resulted in an incidence of 1.74 per 100,000 (95% CI 1.30-2.27). CVT incidence was higher in women (2.13 per 100,000, 95% CI 1.47-2.07). There was a statistically significant difference in LHS between patients with different intracranial complications (Kruskal-Wallis, p = 0.008). The discharge mRS correlated with increasing age (rs = 0.334, p = 0.015), transient risk factors (Fisher's exact test, p = 0.023) and intracranial complications (Fisher's exact test, p = 0.022). In addition, the mRS at 3 months was statistically associated with increasing age (rs = 0.372, p = 0.006) and transient risk factors (Fisher's exact test, p = 0.012). In-hospital mortality was 5.7%, and mortality at follow up was 7.5%, with higher rates in women (5.9% and 8.8%, respectively). Our findings may provide insight regarding the epidemiological features of certain patient groups more prone to developing CVT and its complications, informing local and central stakeholders' efforts to improve standards of care.

Comprehensive Cardiovascular Magnetic Resonance-Derived Myocardial Strain Analysis Provides Independent Prognostic Value in Acute Myocarditis.

Background Late gadolinium enhancement and left ventricular (LV) ejection fraction on cardiovascular magnetic resonance (CMR) are prognostic markers, but their predictive value for incident heart failure or life-threatening arrhythmias in acute myocarditis patients is limited. CMR-derived feature tracking provides a more sensitive analysis of myocardial function and may improve risk stratification in myocarditis. In this study, the prognostic value of LV, right ventricular, and left atrial strain in acute myocarditis patients is evaluated. Methods and Results In this multicenter retrospective study, patients with CMR-proven acute myocarditis were included. The primary end point was occurrence of major adverse cardiovascular events: all-cause mortality, heart transplantation, heart failure hospitalizations, and life threatening arrhythmias. LV global longitudinal strain, global circumferential strain and global radial strain, right ventricular-global longitudinal strain and left atrial strain were measured. Unadjusted and adjusted cox proportional hazard regression analysis were performed. In total, 162 CMR-proven myocarditis patients were included (41 ± 17 years, 75% men). Mean LV ejection fraction was 51 ± 12%, and 144 (89%) patients had presence of late gadolinium enhancement. Major adverse cardiovascular events occurred in 29 (18%) patients during a follow-up of 5.5 (2.2-8.3) years. All LV strain parameters were independent predictors of outcome beyond clinical features, LV ejection fraction and late gadolinium enhancement (LV-global longitudinal strain: hazard ratio [HR] 1.07, P=0.02; LV-global circumferential strain: HR 1.15, P=0.02; LV-global radial strain: HR 0.98, P=0.03), but right ventricular or left atrial strain did not predict outcome. Conclusions CMR-derived LV strain analysis provides independent prognostic value on top of clinical parameters, LV ejection fraction and late gadolinium enhancement in acute myocarditis patients, while left atrial and right ventricular strain seem to be of less importance.

Mass Measurements of Neutron-Deficient Yb Isotopes and Nuclear Structure at the Extreme Proton-Rich Side of the N=82 Shell.

High-accuracy mass measurements of neutron-deficient Yb isotopes have been performed at TRIUMF using TITAN's multiple-reflection time-of-flight mass spectrometer (MR-TOF-MS). For the first time, an MR-TOF-MS was used on line simultaneously as an isobar separator and as a mass spectrometer, extending the measurements to two isotopes further away from stability than otherwise possible. The ground state masses of ^{150,153}Yb and the excitation energy of ^{151}Yb^{m} were measured for the first time. As a result, the persistence of the N=82 shell with almost unmodified shell gap energies is established up to the proton drip line. Furthermore, the puzzling systematics of the h_{11/2}-excited isomeric states of the N=81 isotones are unraveled using state-of-the-art mean field calculations.

Human gingival fibroblast proliferation on materials used for dental implant abutments: a systematic review.

PURPOSE: To conduct a systematic review to evaluate the influence of materials and surfaces used for dental implant abutments on the proliferation of human gingival fibroblasts. MATERIALS AND METHODS: The focus question of this review was: Which material/surface characteristics used for dental implant abutments influence/enhance proliferation of human gingival fibroblasts? The Medline/PubMed, Embase, and Cochrane Library databases were searched using "gingiva," "fibroblasts," "proliferation," and "dental implant abutments" as main keywords with AND/OR as Boolean operators. In vitro studies reporting 3 to 4 or 6 to 7 days of cell proliferation, surface hydrophilicity, and roughness were included. A quality assessment of the selected studies was performed using the web-based Science in Risk Assessment and Policy (SciRAP) tool. RESULTS: The search identified 1,144 studies, and 44 were eligible for inclusion. The average reporting quality SciRAP score was 82.87 ± 10.68, and the average methodologic quality SciRAP score was 87.35 ± 10.55. Machined, polished, and coated titanium and zirconia surfaces were most commonly investigated. Several studies analyzed aluminum oxide, cobalt-chrome-molybdenum alloy, lithium disilicate, polyether ether ketone, polymer-infiltrated ceramic network, and bioglass. The best cell proliferation was observed on zirconia and on titanium harboring nanotubules or microgrooves. UV treatment, polydopamine, and nitride coatings also improved cell proliferation. Due to the heterogeneity of the data, no correlation could be established between cell profileration and surface hydrophilicity or roughness. However, surface roughness in the range of Ra = 15 to 145 nm and Sa = 19 to 500 nm on titanium and zirconia proved most suitable. CONCLUSION: Titanium surfaces with directional guidance patterning and zirconia surfaces best supported cell proliferation during the first week of cell culture. Lack of standardization in surface definitions (machined or polished), methodology, and reporting prevented analytical comparison and should be imposed in future studies.

A high temperature dual-mode quartz crystal microbalance technique for erosion and thermal desorption spectroscopy measurements.

An improved quartz crystal microbalance measurement method is described, which allows us to determine erosion, implantation, and release rates of thin films, during changing temperatures and up to 700 K. A quasi-simultaneous excitation of two eigenmodes of the quartz resonator is able to compensate for frequency drifts due to temperature changes. The necessary electronics, the controlling behavior, and the dual-mode temperature compensation are described. With this improved technique, quantitative in situ temperature-programmed desorption measurements are possible and the quartz crystal microbalance can be used for quantification of thermal desorption spectroscopy measurements with a quadrupole mass spectrometer. This is demonstrated by a study of the retention and release behavior of hydrogen isotopes in fusion-relevant materials. We find that more than 90% of the deuterium implanted into a thin film of beryllium is released during a subsequent temperature ramp up to 500 K.

Prospective Evaluation of a Tumor Control Probability Model Based on Dynamic 18F-FMISO PET for Head and Neck Cancer Radiotherapy.

Our purpose was to evaluate an imaging parameter-response relationship between the extent of tumor hypoxia quantified by dynamic 18F-fluoromisonidazole (18F-FMISO) PET/CT and the risk of relapse after radiotherapy in patients with head and neck cancer. Methods: Before a prospective cohort of 25 head and neck cancer patients started radiotherapy, they were examined with dynamic 18F-FMISO PET/CT 0-240 min after tracer injection. 18F-FMISO image parameters, including a hypoxia metric, MFMISO, derived from pharmacokinetic modeling of dynamic 18F-FMISO and maximum tumor-to-muscle ratio (TMRmax) at 4 h after injection, gross tumor volume (GTV), relative hypoxic volume based on MFMISO, and a logistic regression model combining GTV and TMRmax, were assessed and compared with a previous training cohort (n = 15). Dynamic 18F-FMISO was used to validate a tumor control probability model based on MFMISO The prognostic potential with respect to local control of all potential parameters was validated using the concordance index for univariate Cox regression models determined from the training cohort, in addition to Kaplan-Meier analysis including the log-rank test. Results: The tumor control probability model was confirmed, indicating that dynamic 18F-FMISO allows stratification of patients into different risk groups according to radiotherapy outcome. In this study, MFMISO was the only parameter that was confirmed as prognostic in the independent validation cohort (concordance index, 0.71; P = 0.004). All other investigated parameters, such as TMRmax, GTV, relative hypoxic volume, and the combination of GTV and TMRmax, were not able to stratify patient groups according to outcome in this validation cohort (P = not statistically significant). Conclusion: In this study, the relationship between MFMISO and the risk of relapse was prospectively validated. The data support further evaluation and external validation of dynamic 18F-FMISO PET/CT as a promising method for patient stratification and hypoxia-based radiotherapy personalization, including dose painting.

HPV vaccination as preventive approach for recurrent respiratory papillomatosis - a 22-year retrospective clinical analysis.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a rare, benign disease of the aerodigestive tract, especially the larynx, caused by infection with the human papillomavirus (HPV) types 6 or 11. Current management focuses on surgical debulking with microdebrider of papillomatous lesions with or without concurrent adjuvant therapy, e.g. Cidofovir®. This retrospective study evaluates the results of patients treated at a department of the university clinic between 1990 and 2012 and compares the results of the conventional treatment with a new treatment approach using adjuvant vaccination with Gardasil®. METHODS: A retrospective Kaplan Maier analysis of n = 24 patients diagnosed and treated with RPR was performed. The records were reviewed for gender, age at the time of first manifestation of disease and time to recurrence. RESULTS: Only n = 2 (15.4%) of the n = 13 vaccinated patients developed a recurrence of the disease after a mean time of 54.9 months (SD: 9.5 months). All patients who were not vaccinated (n = 11; 100%) developed a relapse after a mean time of 12.3 months (SD: 9.72 months). CONCLUSION: We propose that adjuvant HPV vaccination with Gardasil® might have a preventive effect in RRP by occluding new papilloma formation.

Low plasma protein Z levels are associated with an increased risk for perioperative bleedings.

BACKGROUND AND OBJECTIVES: Protein Z (PZ) deficiency has been implicated both in bleeding diatheses and in thrombophilia. Considering its ambiguous nature and the conflicting clinical data so far, we set out to evaluate the impact of low PZ on perioperative bleeding in patients who underwent surgical (ENT) interventions involving a high risk of bleeding. PATIENTS AND METHODS: After exclusion of other coagulation disorders, 154 Patients were stratified into quartiles according to PZ plasma concentrations to evaluate the relation between PZ and bleeding complications. RESULTS: Low PZ levels were associated with increased blood loss (P < .001), increased need for blood transfusions (P < .001), and a higher rate of surgical revisions (P = .009) in a concentration-dependent fashion. Low PZ caused earlier (within 24 hours) and repetitive bleedings (P = .005). The number of major bleeding episodes was significantly increased when low PZ was combined with bleeding history (P < .05). Finally, ROC analyses confirmed the predictive value of low PZ for bleeding complications and PZ-thresholds for clinical practice were determined. CONCLUSIONS: Low PZ appears to be an underestimated risk factor for perioperative bleeding. Determination of PZ plasma concentrations might be useful in the preoperative workup in patients with a bleeding history, when detailed clotting analyses remain inconclusive.

SDF-1/CXCR4 expression is an independent negative prognostic biomarker in patients with head and neck cancer after primary radiochemotherapy.

INTRODUCTION: Preclinical and clinical data suggest that the chemokine pathway governed by SDF-1 and CXCR4 contributes to a resistant phenotype. This retrospective biomarker study aims to explore the specific prognostic value of SDF-1 and CXCR4 expression in locally advanced head and neck squamous cell carcinomas (HNSCC) treated with primary radiochemotherapy (RT-CT). MATERIAL AND METHODS: Biopsies from 141 HNSCC tumours of the oral cavity, oropharynx and hypopharynx were evaluated for SDF-1 and CXCR4 expression by immunofluorescence. SDF-1 and CXCR4 expression was correlated with clinico-pathological characteristics and outcome after RT-CT. RESULTS: Patients with tumours exhibiting overexpression of intracellular SDF-1 and CXCR4 have a higher risk for loco-regional relapse and a worse overall survival after RT-CT (multivariate analysis, hazard ratio 2.33, CI [1.18-4.62], p = 0.02 and hazard ratio 2.02, CI [1.13-3.59], p = 0.02, respectively). Similar results were observed when only the subgroup of HPV DNA negative patients were analysed (hazard ratio 2.23 and 2.16, p = 0.02 and p = 0.01, respectively). CONCLUSIONS: Our data support the importance of SDF-1 and CXCR4 expression for loco-regional control and overall survival in HNSCC after primary radiochemotherapy. Prospective multivariate validation and further studies into CXCR4 inhibition to overcome radiation resistance are warranted.