POLAR Study Revisited: Therapeutic Hypothermia in Severe Brain Trauma Should Not Be Abandoned.

The benefits of therapeutic hypothermia (TH) in severe traumatic brain injury (sTBI) have been long debated. In 2018, the POLAR study, a high-quality international trial, appeared to end the debate by showing that TH did not improve mortality in sTBI. However, the POLAR-based recommendation to abandon TH was challenged by different investigators. In our recent meta-analysis, we introduced the cooling index (COIN) to assess the extent of cooling and showed that TH is beneficial in sTBI, but only when the COIN is sufficiently high. In the present study, we calculated the COIN for the POLAR study and ran a new meta-analysis, which included the POLAR data and accounted for the cooling extent. The POLAR study targeted a high cooling extent (COIN of 276°C × h; calculated for 72 h), but the achieved cooling was much lower (COIN of 193°C × h)-because of deviations from the protocol. When the POLAR data were included in the COIN-based meta-analysis, TH had an overall effect of reducing death (odds rate of 0.686; p = 0.007). Among the subgroups with different COIN levels, the only significantly decreased odds rate (i.e., beneficial effect of TH) was observed in the subgroup with high COIN (0.470; p = 0.013). We conclude that, because of deviations from the targeted cooling protocol, the overall cooling extent was not sufficiently high in the POLAR study, thus masking the beneficial effects of TH. The current analysis shows that TH is beneficial in sTBI, but only when the COIN is high. Abandoning the use of TH in sTBI may be premature.

Follicular fluid progesterone concentration is associated with fertilization outcome after IVF: a systematic review and meta-analysis.

Follicular fluid is a key biochemical environment for oocyte development. The potential effect of follicular progesterone level on successful fertilization is a subject of debate, and so the aim of this study was to provide a summary of the currently available evidence on the association between follicular fluid progesterone level and fertilization outcome. To do so, a systematic review and a meta-analysis were performed, with the literature searches being conducted in three databases (PubMed, Embase and the Cochrane Library) to identify all relevant studies published up to 19 August 2017. Data were available from 13 studies (four intracytoplasmic sperm injection [ICSI] and nine conventional IVF) and 1009 individually aspirated follicular fluid samples were included in the analysis. The progesterone levels in follicular fluid were significantly higher in normal fertilization than in failed fertilization, both in conventional IVF (33% difference, P < 0.001) and ICSI (34% difference, P = 0.004). Although these data show that fertilized oocytes are derived from follicles with higher levels of progesterone, the results must be interpreted with caution, because of various progesterone measurement methods and different treatment protocols and it is too early to state that follicular fluid progesterone level could be considered as a marker for oocyte quality.

Metformin induces significant reduction of body weight, total cholesterol and LDL levels in the elderly - A meta-analysis.

BACKGROUND: Metformin is the first-choice drug for patients with Type 2 diabetes, and this therapy is characterized by being weight neutral. However, in the elderly an additional unintentional weight loss could be considered as an adverse effect of the treatment. OBJECTIVES: We aimed to perform a meta-analysis of placebo-controlled studies investigating the body weight changes upon metformin treatment in participants older than 60 years. MATERIALS AND METHODS: PubMed, EMBASE and the Cochrane Library were searched. We included at least 12 week-long studies with placebo control where the mean age of the metformin-treated patients was 60 years or older and the body weight changes of the patients were reported. We registered our protocol on PROSPERO (CRD42017055287). RESULTS: From the 971 articles identified by the search, 6 randomized placebo-controlled studies (RCTs) were included in the meta-analysis (n = 1541 participants). A raw difference of -2.23 kg (95% CI: -2.84 --1.62 kg) body weight change was detected in the metformin-treated groups as compared with that of the placebo groups (p<0.001). Both total cholesterol (-0.184 mmol/L, p<0.001) and LDL cholesterol levels (-0.182 mmol/L, p<0.001) decreased upon metformin-treatment. CONCLUSIONS: Our meta-analysis of RCTs showed a small reduction of body weight together with slight improvement of the blood lipid profile in patients over 60 years. With regard to the risk of unintentional weight loss, metformin seems to be a safe agent in the population of over 60 years. Our results also suggest that metformin treatment may reduce the risk of major coronary events (-4-5%) and all-cause mortality (-2%) in elderly diabetic populations.

Bidirectional Relationship Between Reduced Blood pH and Acute Pancreatitis: A Translational Study of Their Noxious Combination.

Acute pancreatitis (AP) is often accompanied by alterations in the acid-base balance, but how blood pH influences the outcome of AP is largely unknown. We studied the association between blood pH and the outcome of AP with meta-analysis of clinical trials, and aimed to discover the causative relationship between blood pH and AP in animal models. PubMed, EMBASE, and Cochrane Controlled Trials Registry databases were searched from inception to January 2017. Human studies reporting systemic pH status and outcomes (mortality rate, severity scores, and length of hospital stay) of patient groups with AP were included in the analyses. We developed a new mouse model of chronic metabolic acidosis (MA) and induced mild or severe AP in the mice. Besides laboratory blood testing, the extent of pancreatic edema, necrosis, and leukocyte infiltration were assessed in tissue sections of the mice. Thirteen studies reported sufficient data in patient groups with AP (n = 2,311). Meta-analysis revealed markedly higher mortality, elevated severity scores, and longer hospital stay in AP patients with lower blood pH or base excess (P < 0.001 for all studied outcomes). Meta-regression analysis showed significant negative correlation between blood pH and mortality in severe AP. In our mouse model, pre-existing MA deteriorated the pancreatic damage in mild and severe AP and, vice versa, severe AP further decreased the blood pH of mice with MA. In conclusion, MA worsens the outcome of AP, while severe AP augments the decrease of blood pH. The discovery of this vicious metabolic cycle opens up new therapeutic possibilities in AP.

Gender difference in the effects of interleukin-6 on grip strength - a systematic review and meta-analysis.

BACKGROUND: Aging sarcopenia characterized by low muscle mass with low muscle strength affects men and women differently. The contribution of interleukin-6 (IL-6) to sarcopenia has been suggested based on a negative correlation between plasma IL-6 and muscle function described by some studies. However, no consensus regarding clinically relevant cut-off criteria has been reached. Another question arises whether pooling male and female data is an accurate way to determine the predictive value of IL-6 in sarcopenia. The present meta-analysis was designed to assess: (1) whether plasma IL-6 in aged populations in fact correlates negatively to muscle strength; (2) whether such a correlation exists both in men and in women; and (3) whether plasma IL-6 shows a gender difference in old age. METHODS: We applied the preferred reporting items for systematic review and meta-analysis protocols (PRISMA). We searched PubMed and Embase for papers that reported data on individuals over 65 without inflammatory diseases. We extracted either separate male and female data on plasma IL-6 along with at least one muscle parameter or correlation coefficient between plasma IL-6 and these parameters. Random effect models calculated with DerSimonian and Laird weighting methods were applied to analyze correlation coefficients and gender difference in plasma IL-6. Egger's test was used to assess the small study effect. RESULTS: Twenty articles out of 468 records identified were suitable for analyses. Plasma IL-6 correlates negatively with grip strength in mixed populations and also separately in men [- 0.25 with 95% confidence interval (CI): - 0.48, - 0.02] and in women (- 0.14 with 95% CI: - 0.24, - 0.03). However, contrary to expectations, men with better muscle condition have higher plasma IL-6 than women of similar age with worse muscle condition (plasma IL-6 male-female difference: 0.25 pg/mL with 95% CI: 0.15, 0.35). CONCLUSION: This is the first study to demonstrate that a higher predictive IL-6 cut-off level should be determined for aging sarcopenia in men than in women.

Detection of high-risk thrombophilia with an automated, global test: the Coagulation Inhibitor Potential assay.

: The diagnosis of thrombophilia is a cost-consuming and time-consuming process, as each defect should be separately investigated. The Coagulation Inhibitor Potential (CIP) assay is a promising new global test, sensitive for most of the hereditary thrombophilias, developed for manual methodology. We adapt the original method to an optical coagulation analyser. By this automation, the test will be easier, faster and more precise, and it also allows carrying out 18 measurements simultaneously. The CIP assay was performed in 126 healthy subjects and 193 patients with different types of hereditary thrombophilia conditions. Detected with conventional laboratory tests high-risk thrombophilia was present in 70 patients: deficiencies of antithrombin (AT) (n = 12), protein C (PC) (n = 14), protein S (PS) (n = 6), homozygous factor V Leiden (FVL) mutation (n = 9) and combined types (n = 29). Low-risk thrombophilia was present in 123 patients: heterozygous FVL (n = 115) and FII G2010A mutation (n = 8). Significantly lower median CIP values were found for AT-,PC-, PS deficiencies, homozygous and heterozygous FVL mutations and combined thrombophilias (P < 0.01) as compared with healthy controls. There was no significant difference between the heterozygous FIIG20210A (P = 0.669) thrombophilia group and the healthy controls. The best performance of the test was achieved at the cut-off value of 90.0 U (area: 0.981) with 96% sensitivity and 92% specificity in the high-risk thrombophilia group estimated by receiver operating characteristic analysis. The new method seems to be appropriate and reliable for the detection of AT-, PC- and PS deficiencies, homozygous FVL mutation and also for combined deficiencies. The automated CIP test is insensitive to FII G2010A mutation.

Therapeutic Whole-Body Hypothermia Reduces Death in Severe Traumatic Brain Injury if the Cooling Index Is Sufficiently High: Meta-Analyses of the Effect of Single Cooling Parameters and Their Integrated Measure.

Therapeutic hypothermia was investigated repeatedly as a tool to improve the outcome of severe traumatic brain injury (TBI), but previous clinical trials and meta-analyses found contradictory results. We aimed to determine the effectiveness of therapeutic whole-body hypothermia on the deaths of adult patients with severe TBI by using a novel approach of meta-analysis. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to February 2017. The identified human studies were evaluated regarding statistical, clinical, and methodological designs to ensure interstudy homogeneity. We extracted data on TBI severity, body temperature, death, and cooling parameters; then we calculated the cooling index, an integrated measure of therapeutic hypothermia. Forest plot of all identified studies showed no difference in the outcome of TBI between cooled and not cooled patients, but interstudy heterogeneity was high. On the contrary, by meta-analysis of randomized clinical trials that were homogenous with regard to statistical, clinical designs, and precisely reported the cooling protocol, we showed decreased odds ratio for death in therapeutic hypothermia compared with no cooling. As independent factors, milder and longer cooling, and rewarming at <0.25°C/h were associated with better outcome. Therapeutic hypothermia was beneficial only if the cooling index (measure of combination of cooling parameters) was sufficiently high. We conclude that high methodological and statistical interstudy heterogeneity could underlie the contradictory results obtained in previous studies. By analyzing methodologically homogenous studies, we show that cooling improves the outcome of severe TBI, and this beneficial effect depends on certain cooling parameters and on their integrated measure, the cooling index.

Pneumoperitoneum induced ischemia-reperfusion injury of the peritoneum - Preconditioning may reduce the negative side-effects caused by carbon-dioxide pneumoperitoneum - Pilot study.

INTRODUCTION: Laparoscopy is more beneficial than the conventional open technique, however the pneumoperitoneum created may have an ischemic side effect. OBJECTIVE: Our aim was to evaluate the protective effects of preconditioning during laparoscopic cholecystectomies (LC). METHODS: 30 patients were randomized into 2 groups: I. PreC (preconditioning: 5 min. inflation, 5 min. deflation, followed by conventional LC), II: LC (conventional LC). Blood samples were taken before hospitalization (C = control), before surgery, after anaesthesia (B.S.), after surgery (A.S.) and 24 hours after the procedure (24 h). Measured parameters were: malondialdehyde (MDA), reduced glutathione (GSH), sulfhydril groups (-SH), superoxide-dismutase (SOD), catalase (CAT), myeloperoxidase (MPO), length of hospitalization and pain (VAS = visual analogue scale). RESULTS: Compared to the BS levels, no significant changes were detected in SOD's activity and MDA levels. GSH concentrations were significantly increased in the PreC group after operation. SH-, MPO, CAT and liver function enzymes were not significantly different. Hospitalization was shorter in the PreC group. Based on the VAS score patients had less pain in the PreC group. CONCLUSION: Significant differences concerning PreC group were found in GSH values. In the PreC group pain decreased by 2-2.5 units following the procedure, 24 h after surgery, and hospitalisation was also significantly shorter. In our pilot study the potential protective effect of preconditioning could be defined.

In middle-aged and old obese patients, training intervention reduces leptin level: A meta-analysis.

BACKGROUND: Leptin is one of the major adipokines in obesity that indicates the severity of fat accumulation. It is also an important etiological factor of consequent cardiometabolic and autoimmune disorders. Aging has been demonstrated to aggravate obesity and to induce leptin resistance and hyperleptinemia. Hyperleptinemia, on the other hand, may promote the development of age-related abnormalities. While major weight loss has been demonstrated to ameliorate hyperleptinemia, obese people show a poor tendency to achieve lasting success in this field. The question arises whether training intervention per se is able to reduce the level of this adipokine. OBJECTIVES: We aimed to review the literature on the effects of training intervention on peripheral leptin level in obesity during aging, in order to evaluate the independent efficacy of this method. In the studies that were included in our analysis, changes of adiponectin levels (when present) were also evaluated. DATA SOURCES: 3481 records were identified through searching of PubMed, Embase and Cochrane Library Database. Altogether 19 articles were suitable for analyses. STUDY ELIGIBILITY CRITERIA: Empirical research papers were eligible provided that they reported data of middle-aged or older (above 45 years of age) overweight or obese (body mass index above 25) individuals and included physical training intervention or at least fitness status of groups together with corresponding blood leptin values. STATISTICAL METHODS: We used random effect models in each of the meta-analyses calculating with the DerSimonian and Laird weighting methods. I-squared indicator and Q test were performed to assess heterogeneity. To assess publication bias Egger's test was applied. In case of significant publication bias, the Duval and Tweedie's trim and fill algorithm was used. RESULTS: Training intervention leads to a decrease in leptin level of middle-aged or older, overweight or obese male and female groups, even without major weight loss, indicated by unchanged serum adiponectin levels. Resistance training appears to be more efficient in reducing blood leptin level than aerobic training alone. CONCLUSIONS: Physical training, especially resistance training successfully reduces hyperleptinemia even without diet or major weight loss.

Sequential and hierarchical chromosomal changes and chromosome instability are distinct features of high hyperdiploid pediatric acute lymphoblastic leukemia.

BACKGROUND: Pathogenesis of the non-random accumulation of extra chromosomes in the low and high hyperdiploid (HeL, HeH) pre-B pediatric acute lymphoblastic leukemia (B-pALL) is largely unknown, and has been clarified with respect only to tetrasomic chromosomes. We analyzed the hierarchy of changes in chromosome number and chromosomal instability, as well as clonal heterogeneity and evolution, in the untreated bone marrow cell samples from 214 B-pALL patients. PROCEDURE: Applying relocation, 2 × 4 color interphase fluorescence in situ hybridization was used to detect copy number alterations (CNAs) of the most commonly involved chromosomes, 4, 6, 10, 14, 17, 18, 21, and X. This approach allowed us to acquire a dataset correlated for all eight parameters. RESULTS: Based on chromosome number, an average of 6.9 and 10.2, whereas according to unique constellation 15.3 and 26.7 subclones could be identified in the HeL and HeH subgroups, respectively. Cluster analysis revealed the order of CNAs to chromosomes was highly conserved, and network analysis indicated changes in chromosome number were sequential for 80-90% of all numerical aberrations. Significant chromosome instability was revealed in both subgroups of leukemia. CONCLUSIONS: Data generated using this new approach indicate that chromosomal instability, which causes heterogeneity in the subclonal landscape, and the sequential changes to chromosome numbers, are both determining factors in the pathomechanism of the hyperdiploid B-pALL. These new observations could prompt research into the mitotic machinery of leukemic cells to identify new therapeutic targets for treating this disease.

Challenges in the evaluation of D-dimer and fibrinogen levels in pregnant women.

INTRODUCTION: Normal pregnancy is associated with hypercoagulable state. Elevated markers of coagulation and fibrinolytic system activation indicate increased thrombin activity and increased fibrinolysis following fibrin formation throughout pregnancy. These changes exceed the biological variability in most cases. Haemostatic reference intervals are generally based on samples from non-pregnant women. Thus, they may not be relevant to pregnant women, a problem that may hinder accurate diagnosis and treatment of haemostatic disorders during pregnancy. The aim of the study was to follow the changes of haemostatic parameters and to establish gestational age-specific reference intervals during normal pregnancy. MATERIALS AND METHODS: Blood samples of 83 pregnant women were collected at gestational weeks 16, 26 and 36. Fibrinogen, D-dimer, and C-Reactive Protein (CRP) were examined. Reference intervals were calculated for fibrinogen, D-dimer tests with two different methods (mean±2 SD or median and 2.5th and 97.5th percentiles with 90% confidence intervals). RESULTS: fibrinogen and D-dimer increased progressively throughout pregnancy. Mean fibrinogen levels were higher than the maximum of the conventional reference interval, already in the 16th week of pregnancy. D-dimer levels were at or above the conventional cutoff point (250ng/mL) throughout the pregnancy in 42% of pregnant women, while in the 36th week 98% of them displayed elevated D-dimer levels. CRP did not increase in normal pregnancy. CONCLUSIONS: There seems to be an emerging need to reconsider fibrinogen and D-dimer values from a different aspect in pregnancy compared to non-pregnant reference intervals. New reference ranges are suggested to be established in pregnancy.

[Ethiopathogenesis of spontaneous primary pneumothorax. Marijuana: cause or a blame?]. / A spontán primer légmell aetiopathogenesiséhez. Marihuána: ok vagy bunbak?

OBJECTIVE: There are contradictory data on chronic lung injury caused by marijuana, which is partially due to insufficient basic research. Anecdotic reports draw attention to an increased rate of primary spontaneous pneumothorax (PSP) among young marijuana smokers, suggesting a causative link. METHODS: A retrospective analysis of 20 patients treated for PSP in our department in the last two years was performed. Demographics, treatment modality and outcome data were analysed. Chi-square, Mann-Whitney and Fisher tests were applied for statistical evaluation. Gender distribution: 16 male, 4 female, age 23.95 ± 4,57 years: min: 18, max: 32. 13/20 patients admitted to be regular cannabis users (CU), among them 11 male, 2 female, age 24.54 ± 4.77 years. Altogether 7/20 patients had a history of previous pneumo-thorax, with a higher recurrence rate among CU (odds ratio 1.56). RESULTS: In the non-cannabis user group (NCU) 3/7 patients were managed with thoracic drainage alone. 4/7 NCH patients needed major surgery, VATS was performed on all 4 patients. 4/13 CU patients were managed with thoracic drainage, 9/13 patients needed thoracotomy (8 VATS, 1 open thoracotomy). We found a shorter drainage time among NCU patients (4.00 ± 1.00 days NCU vs 4.5 ± 1.73 days CU, p = 0.651). Operative treatment was needed more frequently among cannabis users (69.23% vs NCU 57.14%, p = 0.651) due to impaired lung expansion. Recurrence was detected in 2 patients after drainage, 1 CU, 1 NCU patients, respectively, both of them were managed with VATS. On histological examination there were no major differences between the two groups, 11/13 of operative cases had pulmonary emphysaema . Based on county demographical and clinical data, there's a higher risk for PSP among cannabis users (odds ratio 3.86). CONCLUSIONS: Despite the small sample size, there seems to be a connection between marijuana use and PSP prevalence. It's unclear if marijuana directly contributes to the development of pneumothorax, or just aggravates a fundamentally fragile lung parenchyma condition. In this group of young patients a more aggressive surgical approach is recommended, considering underlying parenchymal impairment and higher recurrence rate.

[The role of neoadjuvant therapy in the treatment of locally advanced squamous cell cancer of the cervical oesophagus]. / A neoadjuváns kezelés szerepe a nyaki szakaszon elhelyezkedo elorehaladott nyelocsolaphámrákok sebészi kezelésében.

INTRODUCTION: Cervical oesophagus represents a critical location for squamous cell carcinoma, which usually requires extensive surgery (pharyngo-laryngo-oesophagectomy). In the last decade, neoadjuvant chemo-radiotherapy was reported to be beneficial in the treatment of locally advanced squamous cell oesophageal cancer. METHODS: Between November 1997 and January 2012, 55 patients with locally advanced (T3-4) squamous cell oesophageal cancer received preoperative chemo-radiotherapy, where the tumour was localized in the upper third. Patients received preoperative irradiation of 3960 cGy in 180 cGy fractions and simultaneously Cisplatin and 5-FU chemotherapy. Restaging was carried out after four weeks and patients considered operable were underwent surgery. RESULTS: In patients with cervical oesophageal cancer 35 of 55 (64%) underwent oesophageal resection or pharyngo-laryngectomy. In 16 out of 35 resected specimens (46%) complete histopathological remission (pCR) was observed. Perioperative mortality and anastomotic leaks were the same: 5/35 (14%). R0 resection rate was 82% and the 2- and 5 years survival rates were 41% and 18%. In 19 cases a larynx preserving pharyngo-oesophagectomy was performed and a free jejunal graft was used for reconstruction after a pharyngo-laryngectomy in 11 cases. CONCLUSION: The high rate of pCR (46%) confirmed that upper third oesophageal cancer has superior sensitivity to multimodal treatment. In 30 cases neoadjuvant chemo-radiotherapy was able to achieve tumour regression and render pharyngo-laryngo-oesophagectomy unnecessary.

Volumetric comparisons of supratentorial white matter hyperintensities on FLAIR MRI in patients with migraine and multiple sclerosis.

Migraine and multiple sclerosis (MS) can both cause white matter lesions that appear similar on conventional MRI. This study aimed to compare these abnormalities, and to find anatomical biomarkers specific for migraine. Supratentorial white matter hyperintensities (WMH) of 17 migraineurs and 15 patients with MS were counted, volumetrically analyzed, and their lobar distribution assessed on fluid-attenuated inversion recovery MRI. We found that migraine WMH affected mainly the deep white matter and subcortical U-fibers, belonged to the anterior circulation, appeared more frequently in the frontal and parietal lobes, showed no difference in average size between lobes, and were smaller and fewer than in MS. Most of the MS WMH were in the frontal lobe and were the smallest average size, while the fewest WMH with the largest size were in the occipital lobe. The pattern of supratentorial WMH appearance differs between the two groups; however, accurate differential diagnosis of WMH by conventional MRI is probably not possible in individual patients.

Assessment of postoperative postvoid residual bladder volume using three-dimensional ultrasound volumetry.

The aim of our prospective study was to assess the concordance between postvoid residual volumes (PVR) of the urinary bladder obtained by two different three-dimensional (3-D) ultrasound (US) volumetric methods (VOCAL and XI VOCAL) and with measurement by the catheter in postoperative patients who have undergone radical hysterectomy. The 3-D sonographic volume-determination of PVR with both methods correlated significantly with the actual amount of PVR by the catheter. The accuracy of both 3-D US volumetric methods was significantly higher under 300 mL of PVR. Bland-Altman plots were generated to examine limits of agreement. Both noninvasive 3-D sonographic methods are appropriate for the correct volume-determination of PVR following radical hysterectomy. Thus, we may avoid routine, albeit often unnecessary, catheterization to measure postoperative residual bladder volumes and subsequently the incidence of lower urinary tract infection may be reduced and better postoperative comfort for patients may be permitted.

Risk factors of migraine-related brain white matter hyperintensities: an investigation of 186 patients.

Brain white matter hyperintensities are more prevalent in migraine patients than in the general population, but the pathogenesis and the risk factors of these hyperintensities are not fully elucidated. The authors analyzed the routine clinical data of 186 migraine patients who were referred to the Outpatient Headache Department of the Department of Neurology, Medical School, University of Pécs, Hungary between 2007 and 2009: 58 patients with white matter hyperintensities and 128 patients without white matter hyperintensities on 3 T MRI. Significant associations between the presence of white matter hyperintensities and longer disease duration (14.4 vs. 19.9 years, p = 0.004), higher headache frequency (4.1 vs. 5.5 attacks/month, p = 0.017), hyperhomocysteinemia (incidence of hyperintensity is 9/9 = 100%, p = 0.009) and thyroid gland dysfunction (incidence of hyperintensity is 8/14 = 57.1%, p = 0.038) were found. These data support the theory that both the disease duration and the attack frequency have a key role in the formation of migraine-related brain white matter hyperintensities, but the effects of comorbid diseases may also contribute to the development of the hyperintensities.

Polymethyl-methacrylate-sorbitol-based capsules as local drug delivery vehicles: a preliminary study.

Local delivery of antibiotics via PMMA (polymethyl-methacrylate) has been widely used in the treatment of chronic osteomyelitis for over 40 years. Unfortunately, PMMA is water insoluble, which seriously limits antibiotic delivery. In addition, the polymerization temperature of PMMA is high, and consequently, only heat-stable antibiotics can be used. Therefore our aim has been to develop an effective antibiotic delivery system, which can be loaded with a wide variety of drugs and deliver the molecules in a predictable manner. Capsules with wall thicknesses of 0.3-0.6 mm from PMMA mixtures containing 40-70 w/w% (weight percent) of sorbitol were prepared and their permeability tested with BPB (Bromophenol Blue). Sorbitol content and wall thickness correlated with the BPB release. SEM (scanning electron microscopy) showed that the canalization of capsules also was well correlated with both sorbitol content and wall thickness. The PMMA-sorbitol-based capsule can potentially be a versatile tool in assuring effective delivery of antibiotics and other substances.

Chemo-radiotherapy in locally advanced squamous cell oesophageal cancer--are upper third tumours more responsive?

Before neoadjuvant therapy was widely applied, the prognosis of oesophageal cancer had been considered dependent on the location of the tumor, i.e. upper third cancers had had the worst prognosis. The aim of this retrolective study was to prove the efficiency of the neoadjuvant treatment, and to compare the response of esophageal cancer in different locations. Between January 1998 and September 2005, 102 patients with locally advanced squamous cell oesophageal cancer received preoperative chemo-radiotherapy. In 40 cases the tumor was located in the upper third and in 62 cases in the middle third of the oesophagus. After a four-week-long treatment free period restaging was carried out and patients considered resectable were submitted to surgery. From 40 patients with upper third oesophageal cancer 28 underwent oesophageal resection or pharyngo-laryngectomy. Thiry-five percent a complete histopathological remission was observed. From 62 patients with middle third oesophageal cancer 43 underwent oesophageal resection. Histological examination of the resected specimens documented complete response only in three patients. The median survival and the R0 resection rate were similar in the two groups. Although the resection rate, perioperative morbidity, mortality and the median survival were similar in the two groups, a significantly higher rate of complete response (p < 0,05) was observed in patients with upper third oesophageal cancer compared to patients with middle third oesophageal cancer. It seems that upper third oesophageal cancer has superior sensitivity to multimodal treatment therefore our results may support that upper third location is not an unfavorable prognostic factor any more.

"Borrelia-associated early-onset morphea": a particular type of scleroderma in childhood and adolescence with high titer antinuclear antibodies? Results of a cohort analysis and presentation of three cases.

BACKGROUND: Morphea is an inflammatory autoimmune skin sclerosis of unknown etiology. A causative role of Borrelia burgdorferi infection has been controversially discussed, but no conclusive solution has yet been achieved. OBJECTIVE: Intrigued by 3 young patients with severe Borrelia-associated morphea and high-titer antinuclear antibodies, we retrospectively examined the relationship between Borrelia exposure, serologic autoimmune phenomena and age at disease onset in morphea patients. METHODS: In 90 morphea patients the presence of Borrelia-specific serum antibodies was correlated to the age at disease onset and the presence and titers of antinuclear antibodies. Patients with active Borrelia infection or high-titer antinuclear antibodies due to systemic sclerosis or lupus erythematosus served as controls. RESULTS: We observed a statistically highly significant association between morphea, serologic evidence of Borrelia infection, and high-titer antinuclear antibodies when disease onset was in childhood or adolescence. LIMITATIONS: Because pathogenic Borrelia species may vary in different geographic regions the relevance of Borrelia infection in morphea induction may show regional variations. CONCLUSION: B burgdorferi infection may be relevant for the induction of a distinct autoimmune type of scleroderma; it may be called "Borrelia-associated early onset morphea" and is characterized by the combination of disease onset at younger age, infection with B burgdorferi, and evident autoimmune phenomena as reflected by high-titer antinuclear antibodies. As exemplified by the case reports, it may take a particularly severe course and require treatment of both infection and skin inflammation.