Comparison of qualitative and quantitative CT and MRI parameters for monitoring of longitudinal spine involvement in patients with multiple myeloma.

PURPOSE: To compare qualitative and quantitative computed tomography (CT) and magnetic resonance imaging (MRI) parameters for longitudinal disease monitoring of multiple myeloma (MM) of the axial skeleton. MATERIALS AND METHODS: We included 31 consecutive patients (17 m; mean age 59.20 ± 8.08 years) with MM, who underwent all baseline (n = 31) and at least one or more (n = 47) follow-up examinations consisting of multi-parametric non-enhanced whole-body MRI (WBMRI) and non-enhanced whole-body reduced-dose thin-section MDCT (NEWBMDCT) between 06/2013 and 09/2016. We classified response according to qualitative CT criteria into progression (PD), stable(SD), partial/very good partial (PR/VGPR) and complete response(CR), grouping the latter three together for statistical analysis because CT cannot reliably assess PR and CR. Qualitative MR-response criteria were defined and grouped similarly to CT using longitudinal quantification of signal-intensity changes on T1w/STIR/ T2*w and calculating ADC-values. Standard of reference was the hematological laboratory (M-gradient). RESULTS: Hematological response categories were CR (14/47, 29.7%), PR (2/47, 4.2%), SD (16/47, 34.0%) and PD (15/47, 29.9%). Qualitative-CT-evaluation showed PD in 12/47 (25.5%) and SD/PR/VGPR/CR in 35/47 (74.5%) cases. These results were confirmed by quantitative-CT in all focal lytic lesions (p < 0.001). Quantitative-CT at sites with diffuse bone involvement showed significant increase of maximum bone attenuation (p < 0.001*) and significant decrease of minimal bone (p < 0.002*) in the SD/PR/VGPR/CR group. Qualitative MRI showed PD in 14/47 (29.7%) and SD/PR/VGPR/CR in 33/47 (70.3%). Quantitative MRI diagnosis showed a statistically significant decrease in signal intensity on short tau inversion recovery sequences (STIR) in bone marrow in patients with diffuse bone marrow involvement achieving SD/PR/VGPR/CR (p < 0.001*). CONCLUSION: Imaging response monitoring using MRI is superior to CT only if qualitative parameters are used, whereas there was no definite benefit from using quantitative parameters with either CT or MRI.

[Catecholamines: pro and contra]. / Katecholamine: Pro und Kontra.

BACKGROUND: Catecholamines with vasopressor and inotropic effects are commonly used in intensive care medicine. The aim of this review is to explain some of the physiologic actions on which a catecholamine therapy is based, but also to elucidate the risks which are associated with an uncritical and excessive use of these drugs. SIDE EFFECTS: Emphasis is placed on the myocardial damage triggered by adrenergic overstimulation. There is considerable evidence that in conditions of severe heart failure, myocardial ischemia as well as cardiogenic and septic shock especially the use of catecholamines with predominant ß-adrenergic effects (epinephrine, dobutamine, dopamine) can have a negative clinical impact. A simple cardiac risk marker might be a tachycardia. ADMINISTRATION: Vasopressor therapy with norepinephrine, based on individually applied perfusion parameters (e.g., urine output, lactate), however, seems justified in many conditions of shock and hemodynamic instability during deep analgosedation. In terms of a cardioprotective therapy, the administration of catecholamines, however, should always be reevaluated and titrated to the minimum deemed necessary.

[Pulmonary infection in neutropenia]. / Pulmonale Infektion bei Neutropenie - Fall 1/2015.

UNLABELLED: MEDICAL HISTORY AND CLINICAL COURSE: A 42-year-old patient with hairy cell leukemia had been treated for 3 years by a hematologist in private practice. Initially the patient received 1 course of cladribine upon which the disease went into complete remission. 6 weeks ago a relapse was diagnosed and combination therapy with cladibrin and rituximab was initiated. Now the patient presented to the emergency room with shortness of breath and pain when breathing. INVESTIGATIONS, TREATMENT AND COURSE: In the chest x-ray, patchy infiltrates and pleural effusions were found on both sides. The subsequently performed computed tomography showed bilateral compactions with an Halo suspicious for fungal infiltrates. Upon admission to the hospital, an empirical antibiotic therapy with clarithromycin and piperacillin/tazobactam was initiated, which was later escalated to meropenem and linezolid. Additionally, an antifungal therapy with voriconazole was started and later switched to liposomal amphotericin B. At his admission, a positive aspergillus antigen could be detected in the microbiological laboratory. Under antimycotic treatment the aspergillus antigen was repeatedly negative. The patient presented with pronounced cytopenias and after a switch of therapy to vemurafenib and filgrastim, the hematopoiesis could only be stimulated insufficiently. The patient was transferred to the intensive care unit three days after admission with severe respiratory failure. He died on day 8 after admission. AUTOPSY AND DIAGNOSIS: Diagnosis was consistent with relapse of hairy cell leukemia with positive BRAF mutation and a bone marrow infiltration > 80 %. Autopsy revealed a significant hepato-splenomegaly, a lack of erythro-, granulo- and thrombopoiesis. Clots interspersed with fungal hyphae were found in both lungs and an infarction of the spleen with evidence of fungal hyphae was detected. The cultural findings post mortem on yeast or mold were negative. CONCLUSION: Patients with refractory hairy cell leukemia and prolonged neutropenia are at increased risk for systemic fungal infections. Therefore, prohylactic antimycotic therapy should be considered early in this group of patients. The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option. In the present case, the patient could unfortunately not be stabilized due to the septic complications.

[End-of life decisions in intensive care units. Influence of patient wishes on therapeutic decision making]. / Therapiezieländerungen auf einer internistischen Intensivstation. Einfluss von Willensäußerungen der Patienten auf Therapieentscheidungen.

BACKGROUND: Among the ethical principles in medicine, respect for patient autonomy has gained the highest revaluation in recent decades. In Germany this was fostered by new legal regulations which came into effect in 2009 and clarified issues regarding end-of-life (EOL) decisions. In this study the influence of direct or mediated wishes of patient wills on EOL decisions in a medical intensive care unit (ICU) were investigated. METHODS: A retrospective analysis of all patients who died in the years 2009-2010 while being treated in the medical ICU of a large German university hospital was carried out. RESULTS: During the observation period 3,401 patients were treated in the ICU of whom 19 % (n=658) died in hospital. Of the 658 patients who died 126 (19 %) had received unlimited therapy, life support was withheld in 241 patients (37 %) and life support was withdrawn in 245 patients (37 %). In 46 patients (7 %) palliative care was instituted from the beginning of the ICU stay. In 104 cases (16 %) the patients themselves made the EOL decision and in 78 cases (12 %) an advance directive was given. A legal healthcare proxy was designated in 8 %. In 541 cases (82 %) the relatives were involved in the EOL decisions. No serious or unsolvable conflicts with relatives were experienced. Involvement of a court of law was not necessary in any of the cases. CONCLUSIONS: In a high percentage of the patients (81 %) who died during the course of intensive care treatment EOL policies were in place. The patients or their relatives were almost always involved in the decision making process. The current German law is in concordance with the established EOL practice in this intensive care unit.

[Hypercalcemic crisis in intensive care]. / Die hyperkalzämische Krise in der Intensivmedizin.

A hypercalcemic crisis is a life-threatening disease with multiorgan failure due to severe hypercalcemia. If left untreated, a hypercalcemic crisis is associated with a very high mortality and requires immediate diagnostic and therapeutic interventions. Especially a rapid rise to high calcium levels impairs the function of several organ systems and leads to central nervous, renal, cardiovascular and gastrointestinal symptoms. A hypercalcemic crisis is caused in more than 90 % by malignancy or primary hyperparathyreoidism and only in very rare cases by other diseases such as granulomatous diseases or other endocrinological diseases. Causal therapeutic options include an adequate treatment of malignancy and a surgical resection of the adenomatous tissue in primary hyperparathyreoidism. In addition, an adequate supportive therapy to lower calcium levels should be initiated as soon as possible. Rehydration with normal saline is the mainstay of therapy. Additional pharmacological therapies include biphosphonates, loop diuretics, calcitonin, steroids and calcimimetics. Besides classic hemodialysis continous renal replacement therapy with citrate anticoagulation is new therapeutical approach that can be used for the acute reduction of elevated serum calcium levels.

[Two autopsy cases with systemic amyloidosis--case 11/2010]. / Zwei Autopsiefälle mit systemischer Amyloidose--Fall 11/2010.

HISTORY AND ADMISSION FINDINGS: A 37-year old patient was admitted with upper abdominal pain, vomiting and diarrhea. A 38-year-old patient was admitted for liver failure. INVESTIGATIONS: Case 1 was diagnosed with an AL amyloidosis due to deposition of the immunoglobulin light chain kappa in all tissues analyzed. In the bone marrow plasma cells were increased to 20-30%. Case 2 suffered from AA amlyoidosis secondary to familial mediterranean fever and underwent dialysis treatment for years. He was positive for hepatitis B and C. DIAGNOSIS, TREATMENT AND COURSE: Patient 1 developed refractory nephrotic syndrome and low blood pressure. During hemodialysis circulatory failure occured and she died during resuscitation. In patient 2 a flare of chronic hepatitis B was found and treated with antiviral therapy. He was referred to ICU for rectal bleeding and developed pulmonary arrest. After resuscitation he died because of lactate acidosis and refractory circulatory failure. Both cases were subjected to autopsy. CONCLUSIONS: The vast majority (90%) of amyloidoses are due to acquired AA or AL amyloidosis. Prognosis remains poor, in particular when cardiac and vascular involvement occurs.

Cushing's disease associated with both pituitary microadenoma and corticotroph hyperplasia.

Herein, we present the case of a 63-year old female patient with initial symptoms of myopathy, hypokaliemia, glucosuria and psychotic symptoms. Laboratory analysis demonstrated elevated plasma levels of ACTH and cortisol. Additionally, urine cortisol excretion was increased approximately 60-fold. MRI imaging revealed a possible pituitary microadenoma. To confirm the diagnosis a bilateral inferior petrosal sinus sampling was performed presenting higher ACTH levels on the right side. However, after surgery cortisol levels did not return to normal range. Histological examination of the tumor revealed a microadenoma. Six days postoperatively, the patient developed several pneumonic infiltrations and fever therefore antibiotic and antifungal therapy was started immediately. In addition aspergillus antigen was elevated. During this septic condition, cortisol levels further increased. The patient died despite optimal intensive care under septical conditions 8 days after surgery. Microbiological analysis identified Aspergillus fumigatus in broncho-alveolar lavage and several organ systems including the heart and brain. Neuropathological autopsy revealed nodular proliferations of corticotropic cells in the pituitary gland that are assumed to be morphological entities between diffuse hyperplasias and adenomas, termed as tumorlets. In single reports, multiple pituitary lesions in patients with Cushing's disease have been demonstrated, but to our knowledge none of these cases presented the combination of an ACTH-producing microadenoma and corticotroph cell hyperplasia in the same patient. Therefore, even after resection of a pituitary microadenoma one should be aware of the possibility of continuously elevated ACTH level being due to multifocal nodular corticotroph hyperplasia which is invisible by neuroradiological examination.

Symptomatic hypoglycemia during imatinib mesylate in a non-diabetic female patient with gastrointestinal stromal tumor.

Imatinib mesylate is a selective competitive inhibitor of the bcr-abl tyrosine kinase and c-KIT. Other kinases, such as phosphatidylinositol- 3'-kinase (PI-3K) involved in insulin signaling, have also been shown to be indirectly affected by imatinib. A recent report described a lowering of blood glucose levels in Type 2 diabetic patients treated with imatinib resulting in a reduction of oral antidiabetic medication or insulin dosage. We present a female non-diabetic patient with a resected gastrointestinal stromal tumor with an increased insulin response following an oral glucose challenge and hypoglycemic episodes following imatinib therapy. In addition to a rise in insulin sensitivity, the patient showed inappropriately high insulin secretion rates in relation to the actual blood glucose concentrations during and after the completion of imatinib treatment. The symptoms suggestive of hypoglycemia such as dizziness and shivering formerly observed in patients treated with imatinib may be related to hypoglycemic glucose concentrations. Physicians treating patients with imatinib should be aware of the possible occurrence of hypoglycemic episodes in non-diabetic patients.

Beta cell function, insulin resistance and plasma adiponectin concentrations are predictors for the change of postprandial glucose in non-diabetic subjects at risk for type 2 diabetes.

Insulin resistance, impaired insulin secretion, and low adiponectin levels have been shown to be predictors for type 2 diabetes. However, it is not yet clear whether these associations (1) are independent of changes in body weight, or (2) are valid for changes in glucose tolerance in the prediabetic state. Sixty-two non-diabetics (50 with normal glucose tolerance) aged 41 +/- 11 years, BMI 30.5 +/- 5.3 kg/m2 (mean +/- SD) were studied twice with a standard oral glucose tolerance test (oGTT, mean follow-up time 3.0 +/- 1.8 years (mean +/- SD) [range 0.5-6.5 years]). Insulin sensitivity and insulin secretion were estimated from oGTT using validated indices. Two-hour blood glucose during oGTT deteriorated over time (baseline 2 h glucose 6.32 +/- 0.21 VS. follow-up 2 h glucose 7.14 +/- 0.22 mM, p < 0.001) while the percentage body fat did not change (32.7 +/- 1.2 VS. 32.6 +/- 1.2%, p = 0.46). Follow-up 2 h blood glucose was predicted by adiponectin (p = 0.01), baseline insulin sensitivity (p = 0.02) and baseline insulin secretion relative to insulin sensitivity (p = 0.03) independent of sex, age, baseline 2 h blood glucose or change in percentage body fat. Our results suggest that low adiponectin levels, insulin resistance and low beta cell function predict the continuous deterioration of glucose tolerance in early prediabetic states, independent of changes in adiposity. Therefore, the early influence of these parameters should be the subject of future prevention programs to prevent deterioration of glucose tolerance.

Association of serum phosphate levels with glucose tolerance, insulin sensitivity and insulin secretion in non-diabetic subjects.

BACKGROUND: Hypophosphatemia is associated with impaired glucose tolerance and insulin resistance in primary hyperparathyroidism. However, little is known about the association between serum phosphate and glucose metabolism in healthy subjects. METHODS: We measured fasting serum phosphate levels (SP, normal range 2.6-4.5 mg/dl) and serum calcium (S-Ca, normal range 2.1-2.6 mmol/l) in 881 non-diabetic subjects (341 male/540 female, age: 38+/-1 years, body mass index 25.9+/-0.2 kg/m(2) (mean+/-standard error of the mean). An oral glucose tolerance test (OGTT) with determination of glucose and insulin every 30 min was performed in all subjects. Insulin secretion and insulin sensitivity (IS) were estimated from the OGTT using validated indices. Furthermore, we tested whether serum phosphate predicts glucose tolerance in 115 subjects during a lifestyle intervention program (LIP). RESULTS: Serum phosphate was negatively correlated with 2-h blood glucose levels independent of age, gender and percent body fat (r=-0.13, P<0.0001). This association remained significant after additional adjustment for S-Ca, creatinine and parathyroid hormone. Serum phosphate was positively correlated with IS (r=0.10, P=0.0006), but not with insulin secretion. This was independent of age, gender, percent body fat, S-Ca and serum creatinine. In the subjects taking part in the LIP low serum phosphate levels at baseline were associated with higher postprandial glucose levels. CONCLUSIONS: In non-diabetic subjects, low serum phosphate levels are associated with high 2-h blood glucose levels and reduced IS. Whether low serum phosphate levels are a cause or a consequence of low IS and impairment of glucose tolerance needs to be tested in further studies.