Rare Histologies and Infrequent Indications for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

AIM: This single-centre study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with rare histologies and uncommon tumour origins. PATIENTS AND METHODS: Prospectively collected data from the data registry of a single institution was retrospectively investigated. We present a series of selected patients who underwent CRS and HIPEC between 2011 and 2021 for peritoneal metastases arising from infrequent tumour entities. RESULTS: The study included 76 patients. From the wide range of histologies, seven groups were formed: Cancer of unknown primary, uncommon ovarian cancer types, other gynaecological tumours (endosalpingiosis, endometrial and cervical cancer), small bowel carcinoma, recurrent peritoneal mesothelioma, desmoplastic small round-cell tumour, and other rare malignancies. The median peritoneal cancer index was 8. Fifty-five patients with primary and 22 patients with recurrent disease were examined. Complete macroscopic tumour resection was achieved in 84% of cases. The median survival was 68.53 months considering the entire cohort, whilst the longest survival rate was registered in the group with rare ovarian cancer, and the shortest in the group of patients with small round-cell tumour, at 112.3 and 11.4 months, respectively (small round-cell tumour versus rare ovarian cancer, hazard ratio=15.6817; 95% confidence interval=2.6585-92.5030; p=0.0024). CONCLUSION: Based on the encouraging results in some test groups, especially in rare ovarian cancer, CUP, small bowel cancer and recurrent mesothelioma, multicenter prospective studies examining such rare tumour histologies are needed to reach a higher number of cases and, thus, explore the impact of multimodal therapy on these patients.

Hyperthermic Intraperitoneal Chemotherapy With Cisplatin and Doxorubicin for 90 Minutes Versus 60 Minutes After Cytoreductive Surgery (CRS). Does the 30-Minute Difference Matter? A Comparative Study in a High Volume Centre.

BACKGROUND/AIM: This study compared the perioperative outcomes after the same combination of hyperthermic intraperitoneal chemotherapy (HIPEC) compounds when administered for 90 min vs. 60 min, while all other therapy variables remained constant. PATIENTS AND METHODS: A total of 120 patients were included with peritoneal surface malignancy who underwent cisplatin (75 mg/m2) and doxorubicin (15 mg/m2) closed HIPEC after cytoreductive surgery. RESULTS: Sixty-five patients (54.2%) in the 60 min and 55 patients (45.8%) in the 90 min HIPEC group were compared. Patients, tumor characteristics, and postoperative complications were comparable. The only significant difference was the rate of chest drain/pleural puncture with an incidence of 18.5% and 34.5% in the 60 min and 90 min group, respectively (p=0.045). After adjustment in a multi-variable regression analysis, the odds for patients with HIPEC 90 min of having chest drain or pleural puncture in comparison to patients with HIPEC 60 min was still higher, but not significant with an OR of 2.238 (95%CI=0.932-5.373; p=0.071). CONCLUSION: HIPEC administered for 90 min is safe and does not increase perioperative morbidity and mortality compared to the 60-min administration.

Renal Recovery after the Implementation of an Electronic Alert and Biomarker-Guided Kidney-Protection Strategy following Major Surgery.

Background: The facilitation of early recovery of acute kidney injury (AKI) is an important step to improve outcome, particularly because of the limited therapeutic interventions currently available for AKI. The combination of an electronic alert and biomarker-guided kidney-protection strategy implemented in the routine care may have an impact on the incidence of early complete reversal of AKI after major non-cardiac surgery. Methods: We studied 294 patients in two cohorts before (n = 151) and after protocol implementation (n = 143). Data collection required 6 months for each cohort. The kidney-protection protocol included an electronic alert to detect patients who were eligible for urinary biomarker [TIMP2 × IGFBP7]-guided kidney-protection intervention. Intervention was stratified according to three levels of immediate AKI risk: low, moderate, and high. After intervention, postoperative changes in the glomerular filtration rate (eGFR) were identified with a tracking software that included an alert for nephrology consultation if the eGFR had declined by >25% from the preoperative reference value. Primary outcome was early AKI recovery, i.e., the complete reversal of any AKI stage to absence of AKI within the first 7 postoperative days. Results: Protocol implementation significantly increased the recovery of AKI (36/46, 78% compared to control 27/48, 56%, (p = 0.025)) and reduced the length of the ICU stay (p < 0.001). There was no significant difference in the overall incidence of all AKI and moderate and severe AKI in the first 7 postoperative days: 46/143 (32%) and 12/151 (8%) in the protocol implementation group compared to 48/151 (32%) and 18/151 (12%) in the historical control group. Patients with AKI reversal within the first 7 postoperative days had lower in-hospital mortality than patients without AKI reversal. Conclusions: Implementing a combined electronic alert and biomarker-guided kidney-protection strategy in routine care improved early recovery of AKI after major surgery.

The basal forebrain cholinergic system in aging and dementia. Rescuing cholinergic neurons from neurotoxic amyloid-ß42 with memantine.

The dysfunction and loss of basal forebrain cholinergic neurons and their cortical projections are among the earliest pathological events in the pathogenesis of Alzheimer's disease (AD). The evidence pointing to cholinergic impairments come from studies that report a decline in the activity of choline acetyltransferase (ChAT) and acetylcholine esterase (AChE), acetylcholine (ACh) release and the levels of nicotinic and muscarinic receptors, and loss of cholinergic basal forebrain neurons in the AD brain. Alzheimer's disease pathology is characterized by an extensive loss of synapses and neuritic branchings which are the dominant scenario as compared to the loss of the neuronal cell bodies themselves. The appearance of cholinergic neuritic dystrophy, i.e. aberrant fibers and fiber swelling are more and more pronounced during brain aging and widely common in AD. When taking amyloid-ß (Aß) deposition as the ultimate causal factor of Alzheimer's disease the role of Aß in cholinergic dysfunction should be considered. In that respect it has been stated that ACh release and synthesis are depressed, axonal transport is inhibited, and that ACh degradation is affected in the presence of Aß peptides. ß-Amyloid peptide 1-42, the principal constituent of the neuritic plaques seen in AD patients, is known to trigger excess amount of glutamate in the synaptic cleft by inhibiting the astroglial glutamate transporter and to increase the intracellular Ca(2+) level. Based on the glutamatergic overexcitation theory of AD progression, the function of NMDA receptors and treatment with NMDA antagonists underlie some recent therapeutic applications. Memantine, a moderate affinity uncompetitive NMDA receptor antagonist interacts with its target only during states of pathological activation but does not interfere with the physiological receptor functions. In this study the neuroprotective effect of memantine on the forebrain cholinergic neurons against Aß42 oligomers-induced toxicity was studied in an in vivo rat dementia model. We found that memantine rescued the neocortical cholinergic fibers originating from the basal forebrain cholinergic neurons, attenuated microglial activation around the intracerebral lesion sides, and improved attention and memory of Aß42-injected rats exhibiting impaired learning and loss of cholinergic innervation of neocortex.

[Significance of ultrasound-measured visceral fat thickness in obesity]. / Ultrahangvizsgálattal mért intraabdominalis zsírvastagság jelentôsége elhízásban.

Ultrasound examination is a simple, easily available method for the measurement of visceral fat thickness. According to the literature, visceral fat thickness correlates well with the computer tomographic determined "gold standard" values of visceral fat quantity, predicting cardiovascular risk of obesity. The probability of indicating the presence of two major risk factors of obesity, fatty liver and cardiovascular complications was investigated by ultrasound. Ultrasound measurement of visceral fat thickness and ultrasound liver attenuation were assessed in 201 patients and correlated with each other and with other parameters. Significant correlation (p<0.001) was found between visceral fat thickness and visceral fat area measured by bioimpedance examinations and body mass index, but no correlation existed between visceral fat thickness, liver ultrasound attenuation and serum lipid level. It was concluded, that presence of fatty liver disease is not certainly connected to the increase of abdominal fat.

Calpain inhibition prevents amyloid-beta-induced neurodegeneration and associated behavioral dysfunction in rats.

Amyloid-beta (Abeta) is toxic to neurons and such toxicity is - at least in part - mediated via the NMDA receptor. Calpain, a calcium dependent cystein protease, is part of the NMDA receptor-induced neurodegeneration pathway, and we previously reported that inhibition of calpain prevents excitotoxic lesions of the cholinergic nucleus basalis magnocellularis of Meynert. The present study reveals that inhibition of calpain is also neuroprotective in an in vivo model of Abeta oligomer-induced neurodegeneration in rats. Abeta-induced lesions of the nucleus basalis induced a significant decrease in the number of cholinergic neurons and their projecting fibers, as determined by analysis of choline-acetyltransferase in the nucleus basalis magnocellularis and cortical mantle of the lesioned animals. Treatment with the calpain inhibitor A-705253 significantly attenuated cholinergic neurodegeneration in a dose-dependent manner. Calpain inhibition also significantly diminished the accompanying neuroinflammatory response, as determined by immunohistochemical analysis of microglia activation. Administration of beta-amyloid markedly impaired performance in the novel object recognition test. Treatment with the calpain inhibitor, A-705253, dose-dependently prevented this behavioral deficit. In order to determine whether pre-treatment with the calpain inhibitor is necessary to exhibit its full protective effect on neurons we induced Abeta toxicity in primary neuronal cultures and administered A-705253 at various time points before and after Abeta oligomer application. Although the protective effect was higher when A-705253 was applied before induction of Abeta toxicity, calpain inhibition was still beneficial when applied up to 1h post-treatment. We conclude that inhibition of calpains may represent a valuable strategy for the prevention of Abeta oligomer-induced neuronal decline and associated cognitive deterioration.

[Association of obesity and depression]. / Az elhízás és a depresszió kapcsolatai.

It has been long known that the frequency of overweight and obese people is higher among depressed and bipolar patients than in the general population. The marked alteration of body weight (and appetite) is one of the most frequent of the 9 symptoms of major depressive episode, and these symptoms occur during recurrent episodes of depression with a remarkably high consequence. According to studies with representative adult population samples, in case of obesity (BMI over 30) unipolar or bipolar depression is significantly more frequently (20-45%) observable. Since in case of depressed patients appetite and body weight reduction is observable during the acute phase, the more frequent obesity in case of depressed patients is related (primarily) not only to depressive episodes, but rather to lifestyle factors, to diabetes mellitus also more frequently occurring in depressed patients, to comorbid bulimia, and probably to genetic-biological factors (as well as to pharmacotherapy in case of medicated patients). At the same time, according to certain studies, circadian symptoms of depression give rise to such metabolic processes in the body which eventually lead to obesity and insulin resistance. According to studies in unipolar and bipolar patients, 57-68% of patients is overweight or obese, and the rate of metabolic syndrome was found to be between 25-49% in bipolar patients. The rate of metabolic syndrome is further increased by pharmacotherapy. Low total and HDL cholesterol level increases the risk for depression and suicide and recent studies suggest that omega-3-fatty acids possess antidepressive efficacy. Certain lifestyle factors relevant to healthy metabolism (calorie reduction in food intake, regular exercise) may be protective factors related to depression as well. The depression- and possibly suicide-provoking effect of sibutramine and rimonabant used in the pharmacotherapy of obesity is one of the greatest recent challenges for professionals and patients alike.

[New features in the recommendations of the Second Hungarian Therapeutic Consensus Conference]. / Aktualitások a cardiovascularis kockázat ertékelésében es a preventív terápián a II. Magyar Terápiás Konszenzus konferencia ajánlásaiban.

The First Hungarian Therapeutic Consensus Conference took place on 3rd Nov. 2003 with the participation of 9 medical societies. Over the past 2 years the results of new major studies have been published and the American ATP III has also updated its guidelines issued in 2004. Based on the above proposals, the Second Hungarian Therapeutic Consensus Conference held on 3rd Nov. 2005 partly confirmed its earlier suggestions, but made some changes as well. Within the high risk category the Conference optionally created a very high risk group from those patients who - in addition to their cardiovascular disease--have either diabetes or metabolic syndrome or acut coronaria syndrome or who are chain smokers. We have included - as a complement - into the asymptomatic high risk category such newly emerging risk factors, one of which already in itself means high risk: ankle/arm index < or = 0.9, GFR <60 ml/min, microalbuminuria (30-300 mg), preclinical atherosclerosis (plaque). Besides, 4 other risk factors were also categorised such as Lp/a (> or = 30 mg/dl), CRP (> or = 3mg/l), homocysteine (> or = 12 micromol), familiarity--atherogenic gene constellation, but only the presence of at least two of these verify high risk. In very high risk group the goals of 3.5 mmol/l and 1.8 mmol/l were determined as therapeutic option. The goal in obese patients--expressed earlier only in BMI--can now be equally determined by the abdominal circumference (94 cm for men, 80 cm for women respectively). ACE inhibitors were recommended earlier as a preventive therapy in case of dysfunction of the left ventricle, while at present they are suggested for all patients with cardiovascular disease. In the recent recommendations guidelines related to nutrition, smoking, exercise have also been included.