Lege Artis Medicinae

[Some thoughts at the 50th anniversary of my medical graduation]

BOGA Bálint

DECEMBER 18, 2012

Lege Artis Medicinae - 2012;22(12)

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Lege Artis Medicinae

[Cost minimization analysis of basal insulin analogues in the treatment of type 2 diabetes]

MERÉSZ Gergő, TABÁK Gy. Ádám, KALÓ Zoltán

[INTRODUCTION - Basal insulin analogues are essential drugs for the treatment of type 2 diabetes mellitus. Basal insulin analogues have been shown to reduce the frequency of hypoglycaemia versus NPH insulin, and thus may be beneficial in the treatment of type 2 diabetes. Here we present a cost-minimisation analysis of basal insulin analogues, comparing insulin glargine and insulin detemir available in Hungary. METHODS - A literature review was conducted to identify randomized, controlled clinical trials with a duration of 12 weeks or more in which a direct comparison of insulin glargine and insulin detemir was made in patients with type 2 diabetes. In a meta-analysis of the eligible trials, the following endpoints were investigated: metabolic status, body weight, frequency of hypoglycaemia, insulin doses administered and the number of insulin injections required. If a high heterogeneity (I2>75%) was found, meta-regression was performed to identify the underlying reasons. The funder’s perspective was applied in the cost-minimization analysis by taking into account the cost of the drug and of medical devices necessary for its administration, based on the daily number of insulin injections. RESULTS - No further studies were found in addition to those included in a metaanalysis published by The Cochrane Library. On the basis of three eligible studies, insulin detemir was injected more frequently compared with glargine (weighted mean difference: 0.42 95% CI 0.14-0.69 injections/day). High heterogeneity was present in case of two endpoints: the incidence of overall hypoglycaemia per patient-year (I2=83%), and daily basal insulin dose in units per body weight (I2=94%). The reason for the high heterogeneity in hypoglycaemia rates was not identified by meta-regression; however, the difference in insulin doses per body weight was negatively associated with body weight (-0.027 IU/kg per 1 kg, 95%CI: -0.051; -0.004). On the basis of the present meta-analysis and meta-regression, our calculations suggest that treating an average weight (90 kg) patient with type 2 diabetes with insulin glargine would result in an annual cost reduction of 93 452 HUF compared with insulin detemir by employing gross public drug prices. CONCLUSION - On the basis of the available clinical evidence, insulin glargine might be a cost-saving alternative of insulin detemir in an average-weight patient with type 2 diabetes. In an era of scarce resources, the role of therapeutic alternatives offering cost savings with the same efficacy become more important. The generalisability of our conclusions might be influenced by potential differences in the manufacturers’ claw-back rate of detemir vs glargine insulin.]

Lege Artis Medicinae

[Is a Good Death Possible? ]

HEGEDÛS Katalin

Lege Artis Medicinae

[Pneumococcal conjugate vaccine for adults: a new paradigm]

LIPTÁK Judit

Lege Artis Medicinae

[The Man who Compiled the First Russian Pharmacopoeia – Keresztély Peken (1730-1779) ]

V. MOLNÁR László

Lege Artis Medicinae

[3rd Congress of the Hungarian Society of Personalized Medicine]

JELINEK Ivett

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Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Clinical Neuroscience

[What happens to vertiginous population after emission from the Emergency Department?]

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[Background – Dizziness is one of the most frequent complaints when a patient is searching for medical care and resolution. This can be a problematic presentation in the emergency department, both from a diagnostic and a management standpoint. Purpose – The aim of our study is to clarify what happens to patients after leaving the emergency department. Methods – 879 patients were examined at the Semmel­weis University Emergency Department with vertigo and dizziness. We sent a questionnaire to these patients and we had 308 completed papers back (110 male, 198 female patients, mean age 61.8 ± 12.31 SD), which we further analyzed. Results – Based on the emergency department diagnosis we had the following results: central vestibular lesion (n = 71), dizziness or giddiness (n = 64) and BPPV (n = 51) were among the most frequent diagnosis. Clarification of the final post-examination diagnosis took several days (28.8%), and weeks (24.2%). It was also noticed that 24.02% of this population never received a proper diagnosis. Among the population only 80 patients (25.8%) got proper diagnosis of their complaints, which was supported by qualitative statistical analysis (Cohen Kappa test) result (κ = 0.560). Discussion – The correlation between our emergency department diagnosis and final diagnosis given to patients is low, a phenomenon that is also observable in other countries. Therefore, patient follow-up is an important issue, including the importance of neurotology and possibly neurological examination. Conclusion – Emergency diagnosis of vertigo is a great challenge, but despite of difficulties the targeted and quick case history and exact examination can evaluate the central or peripheral cause of the balance disorder. Therefore, to prevent declination of the quality of life the importance of further investigation is high.]

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A rare entity of acquired idiopathic generalised anhidrosis which has been successfully treated with pulse steroid therapy: Does the histopathology predict the treatment response?

ÖKTEM Özdemir Ece, ÇANKAYA Şeyda, UYKUR Burak Abdullah, ERDEN Simsek Nazan, YULUG Burak

Acquired idiopathic generalised anhidrosis is an uncommon sweating disorder characterized by loss of sweating in the absence of any neurologic, metabolic or sweat gland abnormalities. Although some possible immunological and structural mechanisms have been proposed for this rare entity, the definitive pathophysiology is still un­clear. Despite some successfully treated cases with systemic corticosteroid application, the dose and route of steroid application are controversial. Here, we present a 41-year-old man with lack of genera­lised sweating who has been successfully treated with high dose pulse intravenous prednisolone. We have discussed his clinical and histopathological findings as well as the treatment options in view of the current literature.

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Simultaneous subdural, subarachnoideal and intracerebral haemorrhage after rupture of a peripheral middle cerebral artery aneurysm

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The cause of intracerebral, subarachnoid and subdural haemorrhage is different, and the simultaneous appearance in the same case is extremely rare. We describe the case of a patient with a ruptured aneurysm on the distal segment of the middle cerebral artery, with a concomitant subdural and intracerebral haemorrhage, and a subsequent secondary brainstem (Duret) haemorrhage. The 59-year-old woman had hypertension and diabetes in her medical history. She experienced anomic aphasia and left-sided headache starting one day before admission. She had no trauma. A few minutes after admission she suddenly became comatose, her breathing became superficial. Non-contrast CT revealed left sided fronto-parietal subdural and subarachnoid and intracerebral haemorrhage, and bleeding was also observed in the right pontine region. The patient had leucocytosis and hyperglycemia but normal hemostasis. After the subdural haemorrhage had been evacuated, the patient was transferred to intensive care unit. Sepsis developed. Echocardiography did not detect endocarditis. Neurological status, vigilance gradually improved. The rehabilitation process was interrupted by epileptic status. Control CT and CT angiography proved an aneurysm in the peripheral part of the left middle cerebral artery, which was later clipped. Histolo­gical examination excluded mycotic etiology of the aneu­rysm and “normal aneurysm wall” was described. The brain stem haemorrhage – Duret bleeding – was presumably caused by a sudden increase in intracranial pressure due to the supratentorial space occupying process and consequential trans-tentorial herniation. This case is a rarity, as the patient not only survived, but lives an active life with some residual symptoms.

Clinical Neuroscience

Autonomic nervous system may be affected after carpal tunnel syndrome surgery: A possible mechanism for persistence of symptoms after surgery

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