Population-Based Effects of Mammography Screening in Bavaria on the Distribution of TNM-T Categories with Respect to Different Histological Subgroups

Background

Organized mammography screening was implemented in Bavaria in 2003, with a target population of about 1.5 million women (aged 50–69 years). We evaluated the population-based effects of mammography screening on the distribution of tumor-node-metastasis (TNM)-T categories with regard to different histological subgroups of breast cancer.

Patients and Methods

Women diagnosed with breast cancer between 2002 and 2008 were included. The annual age-specific incidence rates separated by T category were calculated for different histological subgroups and plotted against time. Time trends were analyzed not only in the screening population but also based on women aged 15–49 and ≥70 years, respectively. Furthermore, correlation coefficients were calculated in order to evaluate the possible association between participation rate and incidence of certain TNM-T categories.

Results

With ductal carcinomas, the incidence of early-stage tumors shows a strong increase in the screening population and a significant correlation with the participation rate, whereas with lobular carcinomas there is a stagnation of incidence in women aged 50–69 years irrespective of TNM-T category.

Conclusions

Short-term effects of mammography screening can already be demonstrated. However, depending on breast cancer type, not all women appear to benefit from screening. The expected long-term reduction of breast cancer mortality remains to be seen.     

Neurofunctional and behavioral correlates of phonetic and temporal categorization in musically trained and untrained subjects

The perception of rapidly changing verbal and nonverbal auditory patterns is a fundamental prerequisite for speech and music processing. Previously, the left planum temporale (PT) has been consistently shown to support the discrimination of fast changing verbal and nonverbal sounds. Furthermore, it has been repeatedly shown that the functional and structural architecture of this supratemporal brain region differs as a function of musical training. In the present study, we used the functional magnetic resonance imaging technique, in a sample of professional musicians and nonmusicians, in order to examine the functional contribution of the left PT to the categorization of consonant-vowel syllables and their reduced-spectrum analogues. In line with our hypothesis, the musicians showed enhanced brain responses in the left PT and superior discrimination abilities in the reduced-spectrum condition. Moreover, we found a positive correlation between the responsiveness of the left PT and the performance in the reduced-spectrum condition across all subjects irrespective of musical expertise. These results have implications for our understanding of musical expertise in relation to segmental speech processing.     

Clinical characteristics of anterior chest wall pain in spondyloarthritis: An analysis of 275 patients

ObjectivesAnterior chest wall pain is a common but little studied feature of spondyloarthritis. The objectives of our study were to assess the prevalence of anterior chest wall pain and to describe its clinical characteristics in a cohort of spondyloarthritis patients in a tertiary care center.MethodsStudy design: retrolective single center observational study in 2010 (COSPA). Consecutive patients with definite spondyloarthritis according to Amor's criteria were included. Data collection: each patient underwent direct interview by a physician. Prevalence of anterior chest wall pain, according to spondyloarthritis subtype and its date of appearance, localization and nature were collected.ResultsIn all, 275 consecutive spondyloarthritis patients were assessed. Among them, 102 patients (37.1%) suffered from spondyloarthritis-associated anterior chest wall pain. It was the first symptom of spondyloarthritis in 3.6% of cases. The prevalence after 5 and 10 years following the diagnosis of spondyloarthritis was 26.0% and 35.5%, respectively. Pain was usually in the upper chest and acute, increased by respiratory movements and movements of the arm; pain during the night was less frequent (41.0%). A flare lasted on average 5 weeks; recurrences were frequent (75%). Non-steroidal anti-inflammatory drugs and anti-tumor necrosis factor agents were reported as effective in 49.3% and 80.0% of cases, respectively.ConclusionAnterior chest wall pain was a frequent manifestation in spondyloarthritis. It occurred early in the disease course, but the risk persisted after disease onset. Better knowledge of the clinical characteristics of this symptom may help physicians for diagnosis and follow-up.     

Isovolaemic hemodilution with gelatin and hydroxyethylstarch 130/0.42: effects on hemostasis in piglets

Objectives: Artificial colloids, frequently used to prevent hemorrhagic shock in children, impair blood coagulation. To determine the impact of acute isovolaemic hemodilution with artificial colloids on clot formation, we conducted an experimental study in a pediatric animal model. Methods: Fifteen piglets underwent hemorrhage by withdrawing 40 ml·kg^?1 of blood volume in steps of 10 ml·kg^?1 each within 1 hour. After each withdrawal, the blood loss was randomly compensated by administering 4% gelatin (GEL) or hydroxylethyl starch 130/0.42 (HES) in a ratio of 1 : 1, or isotonic crystalloid solution (ICS) in a ratio of 1 : 4 for isovolaemic hemodilution. Quality of clot formation and platelet function was measured using Thrombelastometry (ROTEM^®) and Multiple electrode impedance aggregometry (Multiplate^®) after 10, 20, and 40 ml·kg^?1 blood replacement. Results: Moderate hemodilution (10–20 ml·kg^?1 blood replacement) caused no significant differences among groups (e.g. INTEM^®‐MCF after 20 ml·kg^?1 blood replacement (ICS vs GEL vs HES, P > 0.05). Profound hemodilution with 40 ml·kg^?1 blood replacement showed a significant difference between ICS and both colloids (P < 0.05), but no significant differences between GEL and HES. Conclusions: Impairment of clot formation by moderate isovolaemic hemodilution did not significantly differ between ICS, GEL, and HES. Profound hemodilution of more than 50% of the estimated blood volume with GEL and HES caused significant impairment of clot formation in comparison to ICS and has to be considered when using high amounts of these synthetic colloids.     

Prognostic factors of postoperative morbidity and mortality in strangulated groin hernia

Objective

Strangulated groin hernia is a serious surgical emergency, as it is associated with high morbidity and mortality (2.6–9?%). This retrospective study aimed to find significant prognostic factors of postoperative morbidity and mortality.

Methods

From January 2000 to August 2011, we analyzed all patients who had undergone surgery in emergency for strangulated groin hernia. Forty-nine patients out of 2,917 were operated on strangulated groin hernia in an emergency.

Results

The occurrence of strangulated hernia during this period was 1.7?%. Thirty patients out of 49 had inguinal (61.2?%) and 19 femoral (38.8?%) strangulated hernias. The median age was 68.9?years?±?15.3. Patients with strangulated femoral hernia were significantly older than those with inguinal hernia (P?=?0.03). There was a significant predominance of men in the inguinal hernia group and a female predominance in the femoral hernia group (P?=?0.001). An additional exploration was performed on 12 patients (24.5?%). This exploration was done through a midline laparotomy in 8 patients, a laparoscopy in a single patient and the hernioscopy technique was beneficial in exploring the peritoneal cavity in 3 patients. Intestinal resection was necessary in 10.2?%. In our experience, 50?% of midline laparotomies were performed without any intestinal resection. Fisher’s test identified midline laparotomy as the only prognostic factor of postoperative morbidity.

Conclusion

First intention exploratory laparotomy in strangulated hernia surgery was, in our study, a major cause of postoperative complication.     

Risk of wound hematoma at carotid endarterectomy under dual antiplatelet therapy

Background and purpose

This study aims to assess perioperative incidence of wound hematoma and bleeding in patients who underwent carotid endarterectomy (CEA) under dual antiplatelet therapy.

Methods

Consecutive patients with initial CEA receiving aspirin, clopidogrel, or a combination of both were subjected to standard patch endarterectomy. Postoperative wound hematoma was assessed as moderate (subcutaneous bleeding, nonspace-occupying hematoma, and oozing suture bleeding) or severe, i.e., needing operative re-exploration.

Results

Six hundred eighty-four (80.9?%) patients with one of the three types of antiplatelet therapy out of 844 patients registered from 1995 to 2010 were enrolled. Wound hematoma occurred in 27 of 112 (24.1?%) patients under combined aspirin and clopidogrel, 33 of 162 (20.4?%) under clopidogrel, and 48 of 410 (11.7?%) under aspirin. Relative risk compared to aspirin was 2.4 (95?% CI, 1.4 to 4.1) for aspirin and clopidogrel and 1.9 (95?% CI, 1.2 to 3.1) for clopidogrel. Severe space-occupying hematoma needing operative re-exploration occurred in four (3.6?%) patients under aspirin and clopidogrel, seven (4.3?%) under clopidogrel, and five (1.2?%) under aspirin. Corresponding relative risks were 3.0 (95?% CI, 0.8 to 11.4) for aspirin and clopidogrel and 3.7 (95?% CI, 1.1 to 11.7) for clopidogrel. Relative risks remained without relevant change after adjustment for potentially confounding variables.

Conclusions

Dual antiplatelet therapy with combined aspirin and clopidogrel as well as clopidogrel is associated with an increased incidence of perioperative wound hematoma compared to aspirin but on an acceptable low level of incidence. The latter may be achieved by adapting operative procedures to more intensive antiplatelet regimes.     

Supplemental intravenous crystalloids for the prevention of postoperative nausea and vomiting: quantitative review

Hypovolaemia after overnight fasting is believed to exacerbate postoperative nausea and vomiting (PONV). However, data on the efficacy of supplemental i.v. crystalloids for PONV prophylaxis are conflicting. We performed a literature search using CENTRAL, MEDLINE, EMBASE, CINAHL, and Web of Science. We included prospective randomized controlled trials that reported PONV event rates in patients receiving supplemental i.v. crystalloids or a conservative fluid regimen after elective surgery under general anaesthesia. Studies were evaluated with regard to random sequence generation, allocation concealment, blinding of participants, personnel, and outcome assessment, incomplete outcome data, and selective reporting. We identified 15 trials (n=787 crystalloids; n=783 conservative fluids). Compared with conservative fluids, i.v. crystalloids reduced the risk of early postoperative nausea (PON) (relative risk 0.73, 95% confidence interval 0.59-0.89; P=0.003), late PON (0.41, 0.22-0.76; P=0.004), and overall PON (0.66, 0.46-0.95; P=0.02). I.V. crystalloids did not reduce the risk of early postoperative vomiting (POV) (0.66, 0.37-1.16; P=0.16) or late POV (0.52, 0.25-1.11; P=0.09), but did reduce overall POV (0.48, 0.29-0.79; P=0.004). I.V. crystalloids did not reduce the risk of early PONV (0.74, 0.49-1.12; P=0.16), but did reduce the risk of late PONV (0.27, 0.13-0.54; P<0.001) and overall PONV (0.59, 0.42-0.84; P=0.003). I.V. crystalloids reduced the need for antiemetic rescue treatment (0.56, 0.45-0.68; P<0.001). In summary, supplemental i.v. crystalloids were associated with a lower incidence of several PONV outcomes. However, a number of PONV outcomes failed to reach statistical significance, perhaps due to the lack of power. Thus, studies sufficiently powered for the less frequent outcomes (e.g. POV) are required.     

Blood preservation. XXXIV. DHA maintains 2,3-DPG and its adverse effect on ATP is reversed with extra phosphate

We have found that the addition of 10 mM inorganic phosphate to DHA in CPD-adenine maintains ATP levels at normal or higher than normal values for six weeks of storage. 2,3-DPG values are slightly lowered by the extra phosphate, but are still maintained at approximately half normal for four weeks by the DHA. The addition of a higher phosphate concentration, 20 mM, to DHA produced lower levels of ATP and 2,3-DPG than those observed with 10 mM phosphate, although both levels were better than in the CPD-adenine control. pH values in this experiment were lowest in the three preservatives containing DHA, probably indicating increased lactate production due to metabolism of this triose sugar, in addition to dextrose present in CPD.     

Protein kinases as targets for anticancer agents: from inhibitors to useful drugs

Many components of mitogenic signaling pathways in normal and neoplastic cells have been identified, including the large family of protein kinases, which function as components of signal transduction pathways, playing a central role in diverse biological processes, such as control of cell growth, metabolism, differentiation, and apoptosis. The development of selective protein kinase inhibitors that can block or modulate diseases caused by abnormalities in these signaling pathways is widely considered a promising approach for drug development. Because of their deregulation in human cancers, protein kinases, such as Bcr-Abl, those in the epidermal growth factor-receptor (HER) family, the cell cycle regulating kinases such as the cyclin-dependent kinases, as well as the vascular endothelial growth factor-receptor kinases involved in the neo-vascularization of tumors, are among the protein kinases considered as prime targets for the development of selective inhibitors. These drug-discovery efforts have generated inhibitors and low-molecular weight therapeutics directed against the ATP-binding site of various protein kinases that are in various stages of development (up to Phase II/III clinical trials). Three examples of inhibitors of protein kinases are reviewed, including low-molecular weight compounds targeting the cell cycle kinases; a potent and selective inhibitor of the HER1/HER2 receptor tyrosine kinase, the pyrollopyrimidine PKI166; and the 2-phenyl-aminopyrimidine STI571 (Glivec(R), Gleevec) a targeted drug therapy directed toward Bcr-Abl, the key player in chronic leukemia (CML). Some members of the HER family of receptor tyrosine kinases, in particular HER1 and HER2, have been found to be overexpressed in a variety of human tumors, suggesting that inhibition of HER signaling would be a viable antiproliferative strategy. The pyrrolo-pyrimidine PKI166 was developed as an HER1/HER2 inhibitor with potent in vitro antiproliferative and in vivo antitumor activity. Based upon its clear association with disease, the Bcr-Abl tyrosine kinase in CML represents the ideal target to validate the clinical utility of protein kinase inhibitors as therapeutic agents. In a preclinical model, STI571 (Glivec(R), Gleevec) showed potent in vitro and in vivo antitumor activity that was selective for Abl, c-Kit, and the platelet-derived growth factor-receptor. Phase I/II studies demonstrated that STI571 is well tolerated, and that it showed promising hematological and cytogenetic responses in CML and clinical responses in the c-Kit-driven gastrointestinal tumors.     

Safety of percutaneous dilational tracheostomy in hematopoietic stem cell transplantation recipients requiring long-term mechanical ventilation

Purpose

Recent reports have shown that the outcome of mechanically ventilated patients after hematopoietic stem cell transplantation (HSCT) has improved. This study was conducted to clarify if percutaneous dilational tracheostomy is safe in this group of patients and to report the outcome of HSCT recipients requiring long-term mechanical ventilation.

Methods

A retrospective review of our 8-year experience with patients with acute respiratory insufficiency after HSCT, requiring long-term mechanical ventilation and percutaneous dilational tracheostomy and an analysis of patient outcomes were made.

Results

Percutaneous dilational tracheostomy was safely performed in all 51 patients. Although 1 patient (2%) developed a pneumothorax that required drainage, stoma infections or severe bleeding complications were not observed. Of the 51 patients in the study, 14 (27%) survived the intensive care unit stay, and 10 of them were ventilated for more than 20 days. The intensive care unit survival rate for the period from 1998 to 2001 was 11% compared with 38% for the period from 2002 to 2005 (P = .053).

Conclusions

Percutaneous dilational tracheostomy can be safely performed on patients with acute respiratory failure after HSCT. This procedure did not result in postoperative wound infections or significant bleeding complications. Furthermore, the results of our study indicate that today even patients with prolonged mechanical ventilation (>20 days) have a chance of long-term survival.