Treatment-specific risk of subsequent malignant neoplasms in five-year survivors of diffuse large B-cell lymphoma.

BACKGROUND: The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors. METHODS: Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression. RESULTS: After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin versus ≤2250 mg/m2/≤150 mg/m2, respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab. CONCLUSION: Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up for rituximab-treated patients.

The prevalence of hepatitis B virus (HBV) among Turkish immigrants in Germany.

AIM: To determine the seroprevalence of Hepatitis B (HBV) among Turkish immigrants living in Germany. SUBJECTS AND METHODS: A cross-sectional, multi-centered study was conducted among 1319 Turkish immigrants who were living in Germany and admitted to the clinics for any reason. Participants were tested for Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (Anti-HBs) and antibodies to hepatitis B core antigen (Anti-HBc). RESULTS: 37.3% of the participants were tested positive for Anti-HBc. Of these, 45.8% percent was showed positivity for anti-HBc. 25.6% of all donors were showed positive results for Anti-HBc. HbsAg seroprevalence was found as 5%. Furthermore, 90% of participants with positive HBsAg had positive results for Anti-HBc. Males had significantly higher rates of Anti-HBc and HBsAg positivity than females. CONCLUSIONS: Turkish immigrants living in Germany represented higher seroprevalence rate of HBV than total population of Germany.

Clinical effects of leucoreduction of blood transfusions.

For many years filtration for removal of leucocytes from red blood cell (RBC) and platelet transfusions was applied for selected patients to prevent cytomegalovirus (CMV) (re)activation, HLA immunisation and recurrent febrile nonhaemolytic transfusion reactions (FNHTR ). Since the 1980s, there was also growing concern about cancer recurrence and postoperative infections. In this review we discuss the studies on possible benefits of leucoreduction. In 2001 the Dutch Health Council decided that all blood products should undergo leucoreduction by filtration, as a precautionary measure to reduce possible transmission of variant Creutzfeld-Jacob disease (vCJD). The incidences of transfusion-transmitted CMV infection, HLA immunisation and FN HTR are decreased by universal leucoreduction. However, transfusion-related immunomodulation with presumed negative effects on cancer immunosurveillance, postoperative infections or aggravating organ failure, investigated in randomised controlled trials, revealed no support for extended indications for leucoreduction. An exception was seen in cardiac surgery where leucoreduction reduced short-term mortality by approximately 50%. The exact mechanism(s) for this effect is (are) not known. Pro-inf lammatory cytokines induced by eucocytecontaining RBC transfusions in combination with the inflammatory response after cardiac surgery may aggravate morbidity and could lead to mortality. In this review we discuss the evidence for the benefits of universal leucoreduction. Based on the available evidence, reversal to the use of buffy-coat depleted RBCs and restricted indications for leucoreduction by filtration (extended with open-heart surgery) is a safe option.

Transfusion-related immunomodulation: a second hit in an inflammatory cascade?

Allogeneic blood transfusions are dose-dependently associated with postoperative complications. Leucocytes present in blood components may play a role in these effects, referred to as transfusion-related immunomodulation. Of 19 randomized controlled trials of the effect of allogeneic leucocytes in transfusions, 13 looked into the effect of leucocyte-containing red blood cells (RBCs) in the surgical setting on the occurrence of postoperative infections and/or mortality. In contrast to conflicting outcomes of the trials in other settings, in cardiac surgery there is evidence that leucocyte-containing RBCs increase postoperative complications associated with mortality. The studies performed in cardiac surgery show less heterogeneity than studies in other surgical interventions and had been conducted either in one or a few participating centres. In this review, we discuss possible explanations for these results in cardiac surgery (as opposed to other settings), which may relate to clinical as well as transfusional factors. We suggest that leucocyte-containing transfusions during and after cardiac surgery add a second insult to the cardiopulmonary bypass procedure-induced systemic inflammatory response.

Treatment of severe psychosis due to ectopic Cushing's syndrome.

Severe psychosis in patients with Cushing's syndrome is rare and generally difficult to treat. We report a 46-yr-old woman suffering from Cushing's syndrome caused by an inoperable ACTH-producing lung carcinoma. She was initially treated with chemotherapy and radiotherapy. Six months later she presented with severe psychosis. Laboratory findings revealed a severe hypokalemia and metabolic alkalosis, which was caused by extremely high serum ACTH (788 ng/l) and cortisol (4.2 micromol/l). She was unresponsive to treatment with conventional antipsychotic drugs; she was therefore sedated and intubated. Treatment was started i.v. with etomidate, which blocks the cortisol synthesis, and orally by nasogastric tube with mifepristone, which competes with cortisol for binding to their receptors. To counteract adrenal insufficiency, she received corticosteroids. After 5 days there was a normalization of the ACTH, cortisol levels, and the metabolic disorders. After discontinuing etomidate she was extubated; there were no signs of psychosis observed. Computed tomography (CT) scan of the brain showed no metastasis, however CT scan of the abdomen showed liver metastasis and bilateral adrenal enlargement. Unfortunately, the clinical situation worsened and the patient died due to progression of the metastasis. This case report demonstrates the efficacy of a treatment of mifepristone with etomidate in a patient with an ectopic ACTH-producing Cushing's syndrome.

Is increased mortality associated with post-operative infections after leukocytes containing red blood cell transfusions in cardiac surgery? An extended analysis.

In two randomized trials in cardiac surgery we observed that leukoreduced allogeneic red blood cell (RBC) transfusions (LR) compared with standard buffy-coat-depleted RBC transfusions (BCD) resulted in lower rates of post-operative infections and mortality. To unravel whether this comprises two independent side effects or could be related complications of allogeneic leukocytes, we performed a re-analysis on the patients of these two trials. For all analyses, homogeneity tests were shown not to be significant. Data on characteristics of post-operative infections, nature of microorganisms, number of transfusions and causes of death in both studies were subjected to an integrated analysis. In both studies combined, 1085 patients had been assigned to prestorage leukoreduced RBCs (LR, n= 542) or standard buffy-coat-depleted RBCs (BCD, n= 543). Post-operative infections were significantly higher in the BCD group [BCD: 34.2% vs. LR: 24.0%, common odds ratios (COR): 1.65, 95% confidence interval (CI): 1.27-2.15], whereas the species of cultured microorganisms and the type of the infections were similar in both randomization arms. Mortality with infections was significantly higher in patients receiving BCD compared with LR (BCD: 5.5% vs. LR: 2.2%, COR: 2.59, 95% CI: 1.31-5.14), whereas mortality without infections was similar in both arms (BCD: 3.9% vs. LR: 3.1%, COR: 1.24, 95% CI: 0.65-2.38). The only cause of death that differed significantly between BCD and LR was the combination of multiple organ dysfunction syndrome with infections. This re-analysis shows that transfusion of leukocytes containing RBCs during cardiac surgery may be associated with more infections with fatal outcome. This should be confirmed in a larger extended analysis or a prospective study.

High prevalence of vitamin D deficiency, secondary hyperparathyroidism and generalized bone pain in Turkish immigrants in Germany: identification of risk factors.

INTRODUCTION: The aim of the study was to determine the prevalence of vitamin D deficiency, secondary hyperparathyroidism (sHPT), generalized bone pain and predictors of vitamin D deficiency in a cohort of 994 healthy adult urban residents (589 males, 405 females; age range: 16-69 years) consisting of 101 Germans, 327 Turkish residents of Turkey and 566 Turkish immigrants living in Germany. METHODS: The mean (+/- standard deviation) for 25-hydroxyvitamin D [25(OH)D] and biointact parathyroid hormone (BioPTH) for the German men and women was 68.4 nmol/l and 26.7 pg/ml, respectively. Turkish residents of Turkey had a mean 25(OH)D and BioPTH of 40.6 nmol/l and 27.5 pg/ml, respectively, whereas Turkish residents of Germany had a 25(OH)D of 38.1 nmol/l and a BioPTH of 35.6 pg/ml. RESULTS: Vitamin D insufficiency was common among Turkish nationals independent of whether they lived in Turkey or Germany; 75% had 25(OH)D levels of <50 nmol/l. Turkish females had a higher prevalence of 25(OH)D deficiency (<25 nmol/l) than Turkish males: 30 and 19% of Turkish females living in Germany and Turkey were severely vitamin D deficient compared to 8% and 6% of Turkish males living in Germany and Turkey, respectively. With respect to BioPTH levels, 31% of Turkish females and 21% of Turkish males had elevated BioPTH levels in contrast to only 15% of females and 4% of males living in Turkey. Unconditional logistic regression analysis identified the most important predictors for low 25(OH)D levels as sex, body mass index, lack of sun exposure and living at a higher latitude. Additionally, wearing a scarf and number of children were found to be an independent risk factor for vitamin D deficiency in Turkish women living in Turkey and Germany. A strong correlation between low 25(OH)D levels and higher rates and longer duration of generalized bone and/or muscle aches and pains (often diagnosed as fibromyalgia) was observed. CONCLUSION: Secondary hyperparathyroidism and vitamin D deficiency was found to be common among Turkish immigrants living in Germany, especially in veiled women. Therefore, the monitoring of vitamin D status--i.e. 25(OH)D and PTH--in Turkish immigrants is warranted and once a deficiency is identified, it should be appropriately treated.

Cost-effectiveness of leucocyte-depleted erythrocyte transfusion in cardiac valve surgery.

Cost-effectiveness of leucodepleted erythrocytes (LD) over buffy-coat-depleted packed cells (PC) is estimated from the primary dataset of a recently reported randomized clinical trial involving valve surgery (+/-CABG) patients. Data on the patient level of 474 adult patients who were randomized double-blind to LD or PC were used in order to calculate the healthcare costs and longevity per patient. The incremental cost-effectiveness ratio (ICER) in net costs per life-year gained was established from the healthcare perspective. Bootstrapping and cost-effectiveness acceptability curves were used in order to determine the confidence interval (CI) of the ICER. The longevity of patients in the PC and LD group was 10.6 and 11.4 years, respectively. Relative to PC, LD yielded an estimated 0.8 (95% CI = -0.27 to 1.84) life-year in the baseline. Adjusted for age and sex differences, health gains for LD are 0.4 life-year gained (95% CI = -0.67 to 1.44). Healthcare costs per patient averaged 10163 US dollars per patient in the PC group and 9949 US dollars in the LD group. Average cost-savings were 214 US dollars (95% CI = -1536 to 1964) per patient. Acceptability curves constructed from bootstrap simulations showed a probability of being cost-saving of 59% for universal leucodepletion from the healthcare perspective. The probability of adopting leucodepletion regardless of the costs reaches 92.7%. LD in patients receiving four or more transfusions showed the highest cost-savings and health gains. Leucodepletion of erythrocytes is a cost-saving strategy in cardiac valve (+/-CABG) patients. However, probablistic analysis failed to show a significant difference with buffy-coat-depleted PC.

Double-blind, randomized controlled trial on the effect of leukocyte-depleted erythrocyte transfusions in cardiac valve surgery.

BACKGROUND: Leukocytes in allogeneic blood transfusions are believed to be the cause of immunomodulatory events. A few trials on leukocyte removal from transfusions in cardiac surgery have been conducted, and they showed inconclusive results. We found in a previous study a decrease in mortality rates and number of infections in a subgroup of more heavily transfused patients. METHODS AND RESULTS: Patients (n=496) undergoing valve surgery (with or without CABG) were randomly assigned in a double-blind fashion to receive standard buffy coat-depleted (PC) or prestorage, by filtration, leukocyte-depleted erythrocytes (LD). The primary end point was mortality at 90 days, and secondary end points were in-hospital mortality, multiple organ dysfunction syndrome, infections, intensive care unit stay, and hospital stay. The difference in mortality at 90 days was not significant (PC 12.7% versus LD 8.4%; odds ratio [OR], 1.52; 95% confidence interval [CI], 0.84 to 2.73). The in-hospital mortality rate was almost twice as high in the PC group (10.1% versus 5.5% in the LD group; OR, 1.99; 95% CI, 0.99 to 4.00). The incidence of multiple organ dysfunction syndrome in both groups was similar, although more patients with multiple organ dysfunction syndrome died in the PC group. LD was associated with a significantly reduced infection rate (PC 31.6% versus LD 21.6%; OR, 1.64; 95% CI, 1.08 to 2.49). In both groups, intensive care unit stay and hospital stay were similar, and postoperative complications increased with the number of transfused units. CONCLUSIONS: Mortality at 90 days was not significantly different; however, a beneficial effect of LD in valve surgery was found for the secondary end points of in-hospital mortality and infections.

Cardiovascular risk factor levels in a lower middle-class community in Ankara, Turkey.

STUDY OBJECTIVE: To assess the prevalence of risk factors for coronary heart disease (CHD) in a lower middle-class urban community of Turkey. DESIGN: Cross-sectional study in an age- and sex-stratified random community sample with equal sample size per stratum. Direct age-standardization using the standard world population to allow international comparison of findings. Logistic regression modelling to identify risk factors for obesity. SETTING: Gülveren, a residential area in Ankara, total population 23,000 persons. PARTICIPANTS: A total of 1672 adults aged 25-64 years and resident in the study community were interviewed, 1272 (76.1%) of those came for physical examination. MAIN RESULTS: The age-standardized prevalence of hypertension according to WHO MONICA criteria was 18.6% (95% confidence interval: 16.1-21.1%) among women and 12.3% (9.7-14.9%) among men; of obesity (body mass index, BMI > or =30 kg/m2) 51.0% (47.6-54.3%) among women and 15.1% (12.0-18.2%) among men; of current smoking 20.1% (17.5-22.6%) among women and 64.8% (61.4-68.2%) among men; of hypercholesterolaemia 20.1% (17.4-22.9%) among women and 13.8% (10.8-16.8%) among men; and of low high density lipoprotein (HDL) 48.4% (44.8-52.1%) among women and 40.6% (36.0-45.2%) among men. In the regression model, age, female sex, non- and ex-smoking were associated with obesity. CONCLUSIONS: The prevalence of smoking, obesity and low HDL is high in this urban, lower middle-class population, even in comparison with industrialized countries. Unexpectedly, women have less favourable CHD risk profiles than men, except for smoking. Preventive action should be community-wide and address the common risk factors simultaneously to avoid replacement effects such as becoming obese after quitting smoking.

Prevalence of risk factors of coronary heart disease in Turks living in Germany: The Giessen Study.

Turkish people represent the majority of immigrants in Germany. Even though a high proportion of Turks has been living in Germany since about 20 years, little is known about risk factors of coronary heart disease (CHD) in this population. In this study a sample of 325 male and 155 female Turks are investigated, who voluntarily underwent a health check-up in Germany. Data about the presence of CHD, risk factors and blood parameters were collected. Mean residence time was 21 and 17 years (males/females). A low percentage of female participants was observed compared to the general Turkish population in Germany. Age adjusted prevalence of CHD reached 9.5% in males and 6.7% in females, respectively. Dyslipoproteinemia (DLP) showed the highest prevalence of all risk factors investigated in both genders. Total cholesterol (TC) levels were comparable to those of other western countries and remarkably higher than reported for the population in Turkey. Besides this, low high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) levels could be found in the majority of the sample. The highest odds ratios for CHD were estimated for stress and hypertension in males and obesity in females. It is concluded that Turkish immigrants in Germany showed an assimilation of lipid pattern to western populations. However, reasons for low HDL-C levels remain unclear. Changes in the lipid metabolism chiefly seem to contribute to the risk factor pattern of Turkish immigrants in Germany.

Laparoscopic abdominal observation method without anesthesia for preventing unnecessary second-look procedures: short report.

Second-look operations after massive intestinal resections secondary to mesenterovascular occlusion are a frequent practice. In about one half of patients who undergo second-look procedures, no intraabdominal intervention is necessary. We present a laparoscopic abdominal observation method to prevent unnecessary laparotomies. In the first operation, two laparoscopic trocars, 5 and 10 mm in diameter, were left in the abdominal wall. After an appropriate time interval, the abdomen was explored laparoscopically through these trocars without anesthesia. If obvious intestinal gangrene and anastomotic leaks were observed laparoscopically, the patients were reoperated on while under general anesthesia; otherwise, the procedure was terminated with removal of the trocars. This method was performed on six patients. Unnecessary relaparotomies were prevented in four patients; intestinal gangrene and anastomotic leaks were not missed in the remaining two patients. A larger patient sample is needed to assess the advantages of this method in preventing unnecessary laparotomies.

Light and electron microscopic examination of exocrine pancreas using zinc iodide-osmium tetroxide technique.

Zinc iodide-osmium tetroxide (ZIO) fixation/staining technique is a metallophilic technique which has been used for the examination of various tissues and cell types. We examined the ZIO (+) cell types in rat exocrine pancreas to obtain further evidence for the significance of the reaction. Among mostly non-reactive pancreatic acinar cells there were ZIO (+) acinar cells of varying staining intensity. Zymogenic granules and centroacinar cells were completely non-reactive. Our electron microscopic findings support the view that the reactivity of the technique used is cell specific but not cell type or organelle specific.

Determinants of coronary reserve in rats subjected to coronary artery ligation or aortic banding.

OBJECTIVE: We investigated whether decreased coronary reserve in hearts after coronary artery ligation or in hearts from rats after aortic banding can be related to remodeling of resistance arteries. METHODS: Maximal coronary flow (absolute flow) and cardiac perfusion (flow corrected for heart weight) were determined in isolated, perfused rat hearts after adenosine or nitroprusside, at 3 and 8 weeks after coronary artery ligation or 4-5 weeks after aortic banding. Perivascular collagen and medial thickness of resistance arteries were determined by morphometry. RESULTS: maximal coronary flow of infarcted hearts had been restored to sham values at 3 weeks. Growth of cardiac muscle mass from 3 to 8 weeks exceeded the increase in maximal coronary flow, leading to a decreased perfusion at 8 weeks. A slight, transient increase in perivascular collagen, but no medial hypertrophy, was found after infarction. After aortic banding perivascular fibrosis and medial hypertrophy led to a decreased maximal coronary flow in both the hypertrophied left and the non-hypertrophied right ventricle. Consequently, perfusion of the left ventricle was most severely reduced. CONCLUSIONS: Reduced maximal perfusion after aortic banding is determined by both cardiac hypertrophy and vascular remodeling. In contrast, during infarction-induced remodeling, reduction of perfusion is not determined by vascular remodeling, but mainly by disproportional cardiac hypertrophy relative to vascular growth.

Complications of 867 thyroidectomies performed in a region of endemic goiter in Turkey.

This article aims to define the incidence of complications in 867 thyroidectomies performed by residents with attending surgeons' supervision as part of a training programme, in a region of endemic goiter. Seven hundred and nine patients were female and 158 were male. The age of the patients ranged between 6 and 76 and mean age was 32.5. Cases were divided into two groups according to their disease nature. Group 1 included 805 patients with nodular colloidal goiter (NCG) and adenomas. The remaining 62 cases, 25 with recurrence of goiter (RG), 21 with thyroid malignancy (TM) and 16 with thyroiditis formed group 2. While the overall complication rate was 11.3% (93 cases) in group 1, it was 20.9% (13 cases) in group 2. The mortality rate was zero in both groups. The incidence of complications of 867 thyroidectomies performed by residents with the attending surgeons' supervision was within acceptable limits especially as far as group 1 was concerned. However we suggested that attending surgeons themselves, disregarding residents training, should perform the operation in special cases such as recurrent goiters, thyroid carcinomas with positive regional lymph nodes and thyroiditis with regional adhesions.

Intestinal obstruction caused by splenic volvulus: report of a case.

Torsion of a wandering spleen is rare, usually presenting as acute abdomen, and is commonly misdiagnosed. In special cases, ultrasonography, arteriography, and additional scintigraphy are extremely valuable in the preoperative diagnostic management. We herein present an unusual case of torsion of a wandering spleen in a 19-year-old female. The presenting symptom was acute gastrointestinal obstruction due to pressure of the enlarged and ptotic spleen in the pelvis. The intestinal obstruction with signs of peritonitis made a laparatomy with removal of the infarcted spleen imperative. After the operation, the patient made a complete recovery.

[Hemodynamic and lung function analytic findings in so-called collagen diseases]. / Hämodynamische und lungenfunktionsanalytische Befunde bei sogenannten Kollagenosen.

Twenty-four patients with connective tissue disease as defined by ARA criteria were submitted to a thorough cardiological and pulmonary diagnostic evaluation. Mean pulmonary arterial pressure was elevated in 54 per cent of the patients, a left-ventricular functional disorder taking the form of elevated pulmonary capillary occlusive pressure was almost equally as frequent. Interindividual comparisons suggest only a low progressivity of the cardiac involvement, while pulmonary involvement progresses rapidly, to become the prognostically predominating factor. This suspicion must be checked by performing follow-up examinations with repeated cath. examinations of the right heart in individual patients. In common with ACE determinations, haemodynamically effective pericardial disorders are of no significance in connective tissue diseases. Patients with "collagenosis" should be submitted to right-heart catheterisation early on. Attempts at therapy taking the form of aggressive treatment of the underlying disease or administration of nitrates or calcium antagonists, would appear meaningful.