A 66-year-old man with hydroxycarbamide induced pneumonitis.

Hydroxycarbamide is used in the treatment of myeloproliferative neoplasms. Hydroxycarbamide is known for its relative lack of severe side effects. Here we present a 66-year-old man with a severe pneumonitis within three weeks after starting him on hydroxycarbamide. He developed life-threatening respiratory failure and was admitted to an intensive care unit. Extensive testing of blood and cultures from sputum and bronchoalveolar lavage fluid did not reveal a pathogenic microorganism. Discontinuation of the drug and treatment with prednisolone resulted in clinical improvement within 2 days. Radiological resolution was confirmed after one month. The clinical course suggests that the pneumonitis was induced by hydroxycarbamide. We want to alert physicians that, in spite of the common assumption that the use of hydroxycarbamide is relatively safe, patients can develop a severe pneumonitis with detrimental outcome and that hydroxycarbamide should be considered a causative agent in the differential diagnosis of pneumonitis.

Efficacy and Safety of Outpatient Treatment Based on the Hestia Clinical Decision Rule with or without N-Terminal Pro-Brain Natriuretic Peptide Testing in Patients with Acute Pulmonary Embolism. A Randomized Clinical Trial.

RATIONALE: Outpatient treatment of pulmonary embolism (PE) may lead to improved patient satisfaction and reduced healthcare costs. However, trials to assess its safety and the optimal method for patient selection are scarce. OBJECTIVES: To validate the utility and safety of selecting patients with PE for outpatient treatment by the Hestia criteria and to compare the safety of the Hestia criteria alone with the Hestia criteria combined with N-terminal pro-brain natriuretic peptide (NT-proBNP) testing. METHODS: We performed a randomized noninferiority trial in 17 Dutch hospitals. We randomized patients with PE without any of the Hestia criteria to direct discharge or additional NT-proBNP testing. We discharged the latter patients as well if NT-proBNP did not exceed 500 ng/L or admitted them if NT-proBNP was greater than 500 ng/L. The primary endpoint was 30-day adverse outcome defined as PE- or bleeding-related mortality, cardiopulmonary resuscitation, or intensive care unit admission. The noninferiority margin for the primary endpoint was 3.4%. MEASUREMENTS AND MAIN RESULTS: We randomized 550 patients. In the NT-proBNP group, 34 of 275 (12%) had elevated NT-proBNP values and were managed as inpatients. No patient (0 of 34) with an elevated NT-proBNP level treated in hospital (0%; 95% confidence interval [CI], 0-10.2%), versus no patient (0 of 23) with a post hoc-determined elevated NT-proBNP level from the direct discharge group (0%; 95% CI, 0-14.8%), experienced the primary endpoint. In both trial cohorts, the primary endpoint occurred in none of the 275 patients (0%; 95% CI, 0-1.3%) subjected to NT-proBNP testing, versus in 3 of 275 patients (1.1%; 95% CI, 0.2-3.2%) in the direct discharge group (P = 0.25). During the 3-month follow-up, recurrent venous thromboembolism occurred in two patients (0.73%; 95% CI, 0.1-2.6%) in the NT-proBNP group versus three patients (1.1%; 95% CI, 0.2-3.2%) in the direct discharge group (P = 0.65). CONCLUSIONS: Outpatient treatment of patients with PE selected on the basis of the Hestia criteria alone was associated with a low risk of adverse events. Given the low number of patients with elevated NT-proBNP levels, this trial was unable to draw definite conclusions regarding the incremental value of NT-proBNP testing in patients who fulfill the Hestia criteria. Clinical trial registered with www.trialregister.nl/trialreg/admin/rctview.asp?TC=2603 (NTR2603).

Complete resolution of autoimmune thyroiditis after R-CHOP in a patient with thyroid lymphoma.

Hashimoto's thyroiditis is a known risk factor for the development of primary thyroid lymphoma. How the treatment of primary thyroid lymphoma influences thyroid function is however largely unknown. This case shows that treatment with R-CHOP chemotherapy can lead to a recovery of thyroid function in a patient with severe hypothyroidism, without thyroid hormone supplementation. Furthermore, this case shows that in patients with primary hypothyroidism and a rapidly enlarging, asymmetrical thyroid, fine needle aspiration should be performed to rule out primary thyroid lymphoma.

Granulocytosis and thrombocytosis in renal cell carcinoma: a pro-inflammatory cytokine response originating in the tumour.

BACKGROUND: In up to 20% of patients with renal cell cancer (RCC) an inflammatory response consisting of low-grade fever, weight loss and an elevated ESR and CRP may occur with modest granulocytosis and thrombocytosis. Clinical and experimental data suggest a pathogenic role for tumour-derived cytokine production, especially interleukin-6. CASE REPORT: A 79-year-old female with RCC presented with low-grade fever, weight loss and overt granulocytosis and thrombocytosis. Radiological examination revealed a right-sided renal tumour. During nephrectomy a gradient between the IL-6 levels in the renal artery and vein was demonstrated, providing direct evidence for in vivo production of IL-6 by the tumour affected kidney, which was confirmed by the demonstration of IL -6 in the tumour cells by immunohistochemical staining and in the supernatant of the homogenised tumour. Cytogenetic examination revealed complex abnormalities including a gain of chromosome 7. In addition we demonstrated production of IL-1alpha, IL-1beta, IL-8 and ICAM-1 in the tumour with systemic elevated levels of IL-6 and IL-8 with secondary increased serum G-CSF and TPO levels. CONCLUSION: We have provided direct evidence for the production of pro-inflammatory cytokines by renal cancer cells in a patient with RCC and a profound inflammatory response, with a central role of IL-6, probably due to a gain of chromosome 7. The extreme granulocytosis and thrombocytosis may have resulted from the secondary systemic production of G-CSF and TPO.

[Diagnostic image (366). A man with haemorrhagic bullae after a fall]. / Diagnose in beeld (366). Een man met hemorragische bullae na een val.

A 71-year-old man with deep venous thrombosis treated with fenprocoumon presented after a trauma with a haematoma due to an INR > 8.0, and later with haemorrhagic bullae, due to venous obstruction.

[A spontaneous haemarthros in a postpartal woman: a case of acquired haemophilia A]. / Een spontane gewrichtsbloeding bij een vrouw post partum: een geval van verworven hemofilie A.

A woman aged 35 years presented with a haemarthros of the left elbow 6 months after her first parturition due to acquired haemophilia A. The bleeding episodes were mild and treated with recombinant activated factor VII. Because of the mild bleeding tendency and the chance of spontaneous remission it was decided to withhold immunosuppressive treatment. During the course of one year, the factor VIII level and the activated partial thromboplastin time (APTT) normalized and the autoantibodies disappeared. Four years after her first parturition, she had an uncomplicated pregnancy and the postpartum period was uneventful. Up to fourteen months postpartum, there are no signs of recurrence of the acquired haemophilia A. Acquired haemophilia A post partum usually presents in the first 3 months post partum. Frequently presenting symptoms are haemorrhages post partum, menorrhagia, soft-tissue haemorrhages and haemorrhages during surgical procedures. As a rule, the haemorrhages are slight. The titers of blocking antibodies are low in comparison with the titers in congenital haemophilia A.

Low cobalamin (vitamin B12) levels in multiple myeloma: a retrospective study.

BACKGROUND: In patients with multiple myeloma a variety of metabolic events may occur. One of these are changes in the serum cobalamin (vitamin B12) concentration. Elevated as well as decreased serum cobalamin levels have been reported. The prevalence and clinical consequences of low cobalamin levels are largely unknown. OBJECTIVE: To investigate the prevalence of low serum cobalamin levels in patients with multiple myeloma and to describe the clinical features, haematological parameters and outcome in patients with multiple myeloma with low and normal serum cobalamin levels. METHODS: A retrospective study was conducted in the Deaconess Hospital in Eindhoven. Thirty-two patients were identified who fulfilled the diagnostic criteria for multiple myeloma and had at least one serum cobalamin level tested during the diagnostic or treatment period. A number of clinical characteristics, haematological parameters and outcome were scored. RESULTS: Twenty-one (66%) patients had a normal serum cobalamin level, nine (28%) patients had a low one and two (6%) patients had an elevated serum cobalamin level. Between the group with a normal and a low serum cobalamin level there were no differences in patients characteristics such as sex and age, tumour characteristics such as the type of paraprotein, tumour load or tumour stage nor in haematological parameters such as haemoglobin level, mean corpuscular volume and megaloblastic changes in the bone marrow. The median survival was not statistically different between both groups.

[Mesenteric panniculitis in a man with abdominal pain, fever and diarrhea]. / Mesenteriale panniculitis bij een man met buikpijn, koorts en diarree.

In a 64-year-old white male with abdominal pain, fever, diarrhoea and weight loss there were radiological signs of mesenteric panniculitis: thickening of the small bowel loops, an infiltrate above the bladder and in the lower right abdomen an ileum loop with a spiculated border, and streaky strands emanating from the mesenteric fat in the lower abdomen. The clinical signs resolved spontaneously with conservative treatment in 3 weeks and after 3 months the radiological abnormalities had disappeared completely. The pathogenesis of mesenteric panniculitis is unknown. The prognosis is favourable. In advanced cases of the disease, anti-inflammatory or immunosuppressive medication may be beneficial.

[The significance of an elevated cobalamin concentration in the blood]. / De betekenis van een te hoge cobalamineconcentratie in het bloed.

Elevated levels of serum cobalamin may be a sign of a serious, even life-threatening, disease. Diseases such as chronic myeloid leukaemia, promyelocytic leukaemia, polycythaemia vera and hypereosinophilic syndrome are often accompanied by markedly elevated levels of cobalamin in the blood. A rise in the serum cobalamin concentration is one of the diagnostic criteria for polycythaemia vera and hypereosinophilic syndrome. In haematological disorders, the increase in circulating cobalamin levels is predominantly caused by enhanced production of haptocorrin. Several liver diseases such as acute hepatitis, cirrhosis of the liver, hepatocellular carcinoma and metastatic liver disease can also be accompanied by an increase in circulating cobalamin. In liver diseases, the increase in cobalamin is predominantly caused by cobalamin release during hepatic cytolysis and/or through decreased clearance of circulating cobalamin by the affected liver. Liver disorders are not an indication for determining the serum cobalamin concentration. However, a coincidentally observed elevated serum cobalamin concentration is reason for further investigation.