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Intravenous paracetamol reduced the use of opioids, extubation time, and opioid-related adverse effects after major surgery in intensive care unit ☆

BACKGROUND This study assessed the analgesic efficacy, side effects, and time to extubation of intravenous paracetamol when administered as an adjuvant to intravenous meperidine after major surgery in intensive care unit (ICU). MATERIAL Patients were randomized postoperatively into 2 groups in ICU. Patients received either 100 mL of serum saline intravenous (IV) every 6 hours and IV meperidine (n = 20 group M) or IV paracetamol 1 g every 6 hours and IV meperidine (n = 20, group MP) into a peripheral vein for 24 hours. Behavioral Pain Scale (BPS) is used until extubation, and visual analog score (VAS) is used after extubation. When BPS and VAS values were more than 4, meperidine, 1 mg/kg IV, was administered and noted in 2 groups. Pain scores, total meperidine consumption, time to extubation, sedation scores, and side effects are 24-hour postoperatively noted. RESULTS Behavioral Pain Scale and VAS scores are significantly lower in group paracetamol-meperidine at 24 hours (P < .05). In group MP, postoperative meperidine consumption (76.75 ± 18.2 mg vs. 198 ± 66.4 mg) and extubation time (64.3 ± 40.6 min vs. 204.5 ± 112.7 min) were lower than in group M (P < .01). In addition to, postoperative nausea-vomiting and sedation scores were significantly lower in group MP when compared with group M (P < .05). CONCLUSION We have demonstrated important clinical benefits by the addition of 4 g/d of paracetamol to meperidine after major surgery. This benefit has been shown in a range of patients under routine clinical conditions and therefore has important practical consequences in ICU. These data suggest that intravenous paracetamol is a useful component of the multimodal analgesia model, especially after major surgery.

Prognostic value DCE-MRI parameters in predicting factor disease free survival and overall survival for breast cancer patients

PURPOSE The aim of the study is to assess the predictive power of DCE-MRI semi-quantitative parameters during treatment of breast cancer, for disease-free (DFS) and overall survival (OS). MATERIALS AND METHODS Forty-nine women (age range, 28-84 years; mean, 50.6 years) with breast cancer underwent dynamic contrast enhancement MRI at 1.0T imaging, using 2D FLASH sequences. Time intensity curves (TICs) were obtained from the regions showing maximal enhancement in subtraction images. Semi-quantitative parameters (TICs; maximal relative enhancement within the first minute, E (max/1); maximal relative enhancement of the entire study, E(max); steepest slope of the contrast enhancement curve; and time to peak enhancement) derived from the DCE-MRI data. These parameters were then compared with presence of recurrence or metastasis, DFS and OS by using Cox regression (proportional hazards model) analysis, linear discriminant analysis. RESULTS The results from of the 49 patients enrolled into the survival analysis demonstrated that traditional prognostic parameters (tumor size and nodal metastasis) and semi-quantitative parameters (E(max/1), and steepest slope) demonstrated significant differences in survival intervals (p<0.05). Further Cox regression (proportional hazards model) survival analysis revealed that semi-quantitative parameters contributed the greatest prediction of both DFS, OS in the resulting models (for E(max/1): p=0.013, hazard ratio 1.022; for stepest slope: p=0.004, hazard ratio 1.584). CONCLUSION This study shows that DCE-MRI has utility predicting survival analysis with breast cancer patients.

Postmastectomy irradiation in breast in breast cancer patients with T1-2 and 1-3 positive axillary lymph nodes: Is there a role for radiation therapy?

BackgroundWe aimed to evaluate retrospectively the correlation of loco-regional relapse (LRR) rate, distant metastasis (DM) rate, disease free survival (DFS) and overall survival (OS) in a group of breast cancer (BC) patients who are at intermediate risk for LRR (T1-2 tumor and 1-3 positive axillary nodes) treated with or without postmastectomy radiotherapy (PMRT) following modified radical mastectomy (MRM).MethodsNinety patients, with T1-T2 tumor, and 1-3 positive nodes who had undergone MRM received adjuvant systemic therapy with (n = 66) or without (n = 24) PMRT. Patient-related characteristics (age, menopausal status, pathological stage/tumor size, tumor location, histology, estrogen/progesterone receptor status, histological grade, nuclear grade, extracapsular extension, lymphatic, vascular and perineural invasion and ratio of involved nodes/dissected nodes) and treatment-related factors (PMRT, chemotherapy and hormonal therapy) were evaluated in terms of LRR and DM rate. The 5-year Kaplan-Meier DFS and OS rates were analysed.ResultsDifferences between RT and no-RT groups were statistically significant for all comparisons in favor of RT group except OS: LRR rate (3%vs 17%, p = 0.038), DM rate (12% vs 42%, p = 0.004), 5 year DFS (82.4% vs 52.4%, p = 0.034), 5 year OS (90,2% vs 61,9%, p = 0.087). In multivariate analysis DM and lymphatic invasion were independent poor prognostic factors for OS.ConclusionPMRT for T1-2, N1-3 positive BC patients has to be reconsidered according to the prognostic factors and the decision has to be made individually with the consideration of long-term morbidity and with the patient approval.

Curcumin attenuates the organ dysfunction caused by endotoxemia in the rat.

OBJECTIVE Curcumin has antioxidant, antitumor, and anti-inflammatory properties. However, it remains unknown whether curcumin has any protective effects on sepsis. The purpose of this study was to demonstrate whether curcumin prevents organ dysfunction in animals with sepsis. METHODS Rats were randomized into four groups. The control group (group I, n = 7) did not receive any treatment. The curcumin group (group II, n = 10) only received 1.2 g/kg of curcumin. Escherichia coli were injected into the remaining groups intraperitoneally after general anesthesia. Five hours after injection, 12 rats received placebo (group III), and 10 rats received 1.2 g/kg of curcumin (group IV) for 7 d. All rats were sacrificed on postsepsis day 8 and a midline laparotomy was performed. Livers, kidneys, and small bowels were excised for evaluation of the degree of inflammation and tissue alterations histopathologically. RESULTS In the liver, widespread hydropic degeneration of hepatocytes were seen in the sepsis group. There was no hydropic degeneration of hepatocytes and no portal inflammation in the sepsis/curcumin group. With respect to the small bowel, the sepsis group showed edema and prominent intraepithelial infiltration of neutrophil leucocytes and plasma cells. Inflammation and hyperemia in the lamina propria in the sepsis/curcumin group were less than those in the sepsis group. With respect to the kidneys, the sepsis group showed severe acute tubular necrosis that was more restricted in the sepsis/curcumin group than in the sepsis group. CONCLUSION Curcumin reduced organ dysfunction in rats with experimentally formed sepsis. We propose that curcumin may be useful in the therapy of organ dysfunction due to sepsis, shock, and other diseases associated with local or systemic inflammation.

The Effects of Different Insufflation Pressures on Liver Functions Assessed with LiMON on Patients Undergoing Laparoscopic Cholecystectomy

Purpose. Laparoscopic cholecystectomy has been accepted as an alternative to laparotomy, but there is still controversy regarding the effects of pneumoperitoneum on splanchnic and hepatic perfusion. We assessed the effects of different insufflation pressures on liver functions by using indocyanine green elimination tests (ICG-PDR). Methods. We analyzed 43 patients who were scheduled for laparoscopic cholecystectomy. The patients were randomly allocated to two groups. In Group I, the operation was performed using 10 mmHg pressure pneumoperitoneum. In Group II, 14 mmHg pressure pneumoperitoneum was used. The ICG-PDR measurements were made after induction (ICG-PDR 1) and after the end of the operation (ICG-PDR 2). Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels were all recorded preoperatively, 1 hour, and postoperative 24 hours after surgery. Results. The ICG-PDR 1 values for Groups I and II were as follows: 26.78 ± 4.2% per min versus 26.01 ± 2.4% per min (P > 0.05). ICG-PDR 2 values were found to be 25.63 ± 2.1% per min in Group I versus 19.06 ± 2.2% per min in Group II (P < 0.05). There was a statistically significant decrease between baseline and postoperative ICG-PDR values in Group II compared to Group I (P < 0.05). Statistically, there was an increase between baseline and postoperative 1st-hour serum AST and ALT level in Group II (P < 0.05) compared to Group I. No statistical differences were detected on postoperative 24st-hour serum AST and ALT levels and all the time bilirubin between groups (P > 0.05). Conclusion. In conclusion, the results show that 14 mmHg pressure pneumoperitoneum decreased the blood flow to the liver and increased postoperative 1st-hour serum AST and ALT levels. We think that 10 mmHg pressure pneumoperitoneum is superior to 14 mmHg pressure pneumoperitoneum in laparoscopic cholecystectomy.

The effect of a flavonoid fractions diosmin + hesperidin on radiation-induced acute proctitis in a rat model

BACKGROUND To explore the protective effect of a flavonoid fractions diosmin + hesperidin (Daflon), against radiation-induced acute proctitis in an experimental rat model. MATERIALS AND METHODS Thirty four rats were divided into four groups. The rats in Group 1 received Daflon and underwent irradiation. The rats in Group 2 received no Daflon and underwent irradiation. The rats in Group 3 received Daflon and underwent sham irradiation. The rats in Group 4 received no Daflon and underwent sham irradiation. Daflon emulsion (100 mg/kg/day) was administered via an orogastric feeding tube to the rats in groups 1 and 3 starting from 1 day prior to irradiation until the euthanasia day (day 15 following irradiation). Radiation therapy was delivered on a cobalt-60 unit using a single fraction of 17.5 Gy defined at a depth of 1 cm through an anterior portal. Slides were examined by the same pathologist under a light microscope two times in a blinded manner. RESULTS When compared to group 2, the rats of Group 1 showed less glandular distortion and less mucosal inflammation with less infiltration of the crypt epithelia by the inflammatory cells (P < 0.001). A statistically significant increase in all parameters but muscular wall thickness was observed for the rats in Group 2 as compared to the group 3 and 4. CONCLUSIONS Administration of a dose of 100 mg/kg/day of the diosmin + hesperidin resulted in decreased morphologic inflammatory changes. This drug may have protective effects against radiation-induced acute proctitis.

Relation between Tc-99m sestamibi uptake and biological factors in hyperparathyroidism

PurposeThe aim of this study was to evaluate the relation between uptake ratios of Tc-99m sestamibi (MIBI) and tumor volume, serum biochemical values (i-PTH, Ca, P) and oxyphil cell content.Materials and MethodsThe study population consisted of 19 patients (2 M, 17 F; mean ± SD: 47 ± 12 y). Anterior planar images of the neck and chest were acquired early (15 min) and triple late phase (1,2 and 3-4 h) after intravenous injections of 740 MBq MIBI. Each of the surgical materials was reviewed retrospectively. The percentage of cell type (chief, oxyphil and clear cells) in the tumors was calculated by light microscopy.ResultsThe uptake ratio obtained from L1 (1 hour) phase was found to be higher than the uptake ratio obtained from early phase, and the difference was statistically significant (1.57 ± 0.34 and 1.43 ± 0.29, p = 0.004, respectively). There was no significant correlation between uptake ratios that were obtained from 4 different imaging phases and lesion volumes, i-PTH levels and calcium levels (p > 0.05). However, there was a significant adverse correlation between L2 and L3 uptake ratios and serum phosphorus values (r = –0.44, p = 0.04 and r = –0.46, p = 0.04, respectively). Additionally, no significant correlation between MIBI uptake ratios of each imaging phase and the laboratory data, volume of lesion or oxyphil percentage volume was found after the multiple regression analysis (E: p = 0.46, r = 0.49; L1: p = 0.24, r = 0.58; L2: p = 0.27, r = 0.57; L3: p = 0.32, r = 0.55, respectively. There was no correlation between gland oxyphil percentage volume and MIBI uptake ratios (p > 0.05).ConclusionThe results of our study show that the optimal imaging times after intravenous injection of MIBI are 15 minutes and 1 hour because of the shorter examination time without loss of diagnostic ability. In the present study, there was no significant correlation between MIBI uptake ratios and increased gland volume, or serum Ca and i-PTH levels. Besides, we think that oxyphil cell content may not have a main effect on MIBI uptake and retention. The fact of an adverse relation between phosphorus and MIBI retention in our study suggests that phosphorus level should be considered prior to MIBI imaging.

Protective effect of curcumin on cyclosporin A-induced endothelial dysfunction, antioxidant capacity, and oxidative damage

Cyclosporin A (CsA) is the most widely used immunosuppressive drug for preventing graft rejection and autoimmune disease. However, the therapeutic treatment induces several side effects such as nephrotoxicity, cardiotoxicity, hypertension, and hepatotoxicity. Curcumin has been successfully used as a potent antioxidant against many pathophysiological states. This experimental study was performed to test, during CsA treatment, the alterations of curcumin antioxidant properties against CsA-induced endothelial dysfunction. Rats were divided into four groups: control, curcumin alone, CsA, and CsA + curcumin; each group containing eight animals. The animals in the CsA + curcumin group were treated with CsA (10 days, 25 mg/kg, orally) and curcumin (15 days, 200 mg/kg, orally, starting 5 days before CsA administration). At the end of the treatments, the animals were killed; serum and aorta tissue were treated for biochemical and morphological analyses. The results indicate that CsA-induced aortic endothelial dysfunction was characterized by morphological and ultrastructural alterations in tissue architecture, changes in malondialdehyde and ferric reducing/antioxidant power levels, and increase in endothelial nitric oxide synthase and terminal-deoxynucleotidyl-transferase mediated dUTP nick end labeling (TUNEL) expression. In conclusion, our data suggest that the imbalance between production of free oxygen radicals and antioxidant defence systems, due to CsA administration, is a mechanism responsible for oxidative stress. Moreover, we show that curcumin plays a protective action against CsA-induced endothelial dysfunction and oxidative stress, as supported by biochemical, ultrastructural, immunohistochemical, and TUNEL results.

Dural sinus vein thrombosis in a patient with colon cancer treated with FOLFIRI/bevacizumab

The adverse effects of regimes in cancer treatment have forced us to change to new targeted therapy options. Understanding these side effects, which can lead to discontinuation of the new therapy strategies, will allow the clinical management of these side effects and result in continuing therapies with effective medications. Bevacizumab, which is an IgG1 antibody against vascular endothelial growth factor, has side effects such as proteinuria, hypertension, venous and arterial thromboembolic events, and hemorrhage. This is the first reported case of dural sinus vein thrombosis, during the treatment with bevacizumab.

Protective effect of everolimus on renal ischemia reperfusion injury in rats.

The aim of this study was to determine the effect of everolimus and tacrolimus pretreatments on renal morphology and function in a rat ischemia reperfusion (I/R) model. Twenty-eight male Sprague-Dawley rats were randomly assigned to saline + sham operation, saline + I/R (IR), tacrolimus + I/R (TRL + I/R) and everolimus + I/R (ERL + I/R) groups. Saline and active treatments were administered intraperitoneally for seven consecutive days before the surgery. The suprarenal aorta was clamped to achieve warm ischemia, except in the sham group. Right nephrectomy was performed in all animals and histology was examined. Renal function was assessed on post-operative Day 7 by Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy, glomerular filtration rate (GFR) and serum biochemistry. Both everolimus and tacrolimus preserved serum creatinine and blood urea nitrogen levels, but only everolimus preserved GFR (0.74 ± 0.36, 1.20 ± 0.37 and 2.24 ± 0.32 mL/min for I/R, TRL + I/R and ERL + I/R, respectively, P < 0.001). %ID values for sham, I/R, TRL + I/R and ERL + I/R were 55 ± 3, 47 ± 4, 45 ± 6 and 62 ± 7 (P < 0.001). On histologic evaluation, ERL + I/R showed less tubular damage and necrosis than I/R, as well as TRL + I/R. Within the confines of this rat warm ischemia model, everolimus pre-treatment was useful in preserving renal function following I/R injury. The possibility of using everolimus as a pre-conditioning agent for I/R injury in kidney transplantation should be further explored.