Extracellular vesicles (EVs) are membranous nanostructures that can indicate undergoing processes in organs and thus help in diagnostics and prognostics. They are secreted by all cells, contained in ...body fluids, and able to transfer proteins, lipids and nucleic acids to distant cells. Intracranial EVs were shown to change their composition after severe traumatic brain injury (TBI) and therefore to have biomarker potential to evaluate brain events. Properties of intracranial EVs early after TBI, however, have not been characterized. Here, we assessed cerebrospinal fluid (CSF) up to seven days after isolated severe TBI for physical properties of EVs and their proteins associated with neuroregeneration. These findings were compared with healthy controls and correlated to patient outcome. The study included 17 patients with TBI and 18 healthy controls. EVs in TBI-CSF were visualized by electron microscopy and confirmed by immunoblotting for membrane associated Flotillin-1 and Flotillin-2. Using nanoparticle tracking analysis, we detected the highest range in EV concentration at day 1 after injury and significantly increased EV size at days 4-7. CSF concentrations of neuroregeneration associated proteins Flotillin-1, ADP-ribosylation Factor 6 (Arf6), and Ras-related protein Rab7a (Rab7a) were monitored by enzyme-linked immunosorbent assays. Flotillin-1 was detected solely in TBI-CSF in about one third of tested patients. Unfavorable outcomes included decreasing Arf6 concentrations and a delayed Rab7a concentration increase in CSF. CSF concentrations of Arf6 and Rab7a were negatively correlated. Our data suggest that the brain response within several days after severe TBI includes shedding of EVs associated with neuroplasticity. Extended studies with a larger number of participants and CSF collected at shorter intervals are necessary to further evaluate neuroregeneration biomarker potential of Rab7a, Arf6, and Flotillin-1.
Psoriasis is considered to be a cytokine-driven immune-mediated disease, although the cell cytotoxicity mechanisms involved remain unrecognized. Herein, we analyzed granulysin expression in different ...lymphocyte subsets of peripheral blood of 40 psoriatic patients (20 with severe and 20 with mild psoriasis) and seven sample of psoriatic skin. The simultaneous detection of intracellular granulysin and cell surface antigens was performed using flow cytometry in peripheral blood and immunohistochemistry in skin lesions. The frequency of granulysin+ cells, mean fluorescence intensity for granulysin, and the frequency of CD8+ T lymphocytes, NK cells, and NKT cells expressing granulysin molecules in peripheral blood were significantly higher in patients with severe psoriasis compared to mild disease and healthy individuals. These were also correlated with disease severity. Furthermore, granulysin+ cells, CD8+granulysin+ T lymphocytes, and CD56+granulysin+ NK cells were present in a higher frequency in the epidermal basal cell layer and in the dermal infiltrate of lesional skin as compared to non-lesional and healthy skin. In conclusion, granulysin+ cytotoxic cells are upregulated in blood and lesions of patients with psoriasis suggesting the involvement of granulysin mediated cytotoxicity in psoriasis pathogenesis.
There are no evidence-based guidelines for volume replacement during surgical procedures such as laparoscopic cholecystectomy. However, the administration of a restrictive volume of crystalloids ...could be more cost-effective and safe. This trial aimed to determine the effectiveness and safety of a restrictive regimen of crystalloids in patients during laparoscopic cholecystectomy by analyzing its cost-effectiveness and 1-year morbidity rate.
In this randomized, prospective study, patients were assigned to one of three groups based on the volume of fluid administered: the restrictive group received 1 mL/kg/hr, the low liberal group received 5 mL/kg/hr, and the high liberal group received 15 mL/kg/hr of Ringer's solution intraoperatively. There were 40 patients in each group. Each patient's hemodynamic parameters and laboratory values (arterial blood gas and lactate levels) were measured together with their consumption of crystalloids, volatile anesthetics, and analgesics.
Analysis of the hemodynamic and laboratory parameters revealed no signs of global hypoperfusion in any of the groups analyzed. There was no significant difference in the duration of surgery and anesthesia, but the consumption of crystalloids, volatile anesthetics, and opioids was significantly lower in the restrictive group, compared with the low and high liberal groups. Although there was no significant difference in the 1-year morbidity among the groups, heart failure was observed in one patient in the high liberal group in the early postoperative period.
Restrictive fluid therapy during laparoscopic cholecystectomy is justified, safe, and more cost-effective than other options.
Summary
In this study to identify prognostic biomarkers for ischemic stroke (IS) outcome, we monitored monocyte number and monocyte chemoattractant protein (MCP-1) concentration in peripheral blood ...of 44 patients with IS during the week following IS. According to the severity of IS, patients were allocated to three groups: patients with transient ischemic attack (TIA), patients with National Institute of Health Stroke Scale (NIHSS) score ≤ 12, and patients with NIHSS > 12. In patients with NIHSS > 12 statistically significant increased number of monocytes was observed on day 7. MCP-1 plasma concentration initially increased, decreased at day 3 in patients with NIHSS > 12 and increased and restored on day 7. A negative correlation between the number of monocytes and MCP-1 concentration was observed on day 3 after IS. Higher day-7 MCP-1 level was associated with higher modified Rankin Scale (mRS) value (indicating worse outcome) at 90 days post-IS in patients with NIHSS > 12. Our findings suggest that number of monocytes and plasma MCP-1 level could be clinical prognostic biomarkers as early predictors of disease outcome in patients with IS.
The aim of this study is to report the first case of simultaneous appearance of cerebral venous thrombosis (CVT) and bilateral subdural hematomas (SDHs) following epidural analgesia for labor and ...delivery and to point out the difficulty of establishing such a diagnosis in the presence of postpartum headache. A 26-year old primigravida with a history of epilepsy received epidural analgesia for delivery. Three days after the uneventful spontaneous vaginal delivery she complained about the headache. Patient responded very well to the pain medication and oral hydration, and the headache was relieved. Ten days after the delivery, the headache reoccurred, and an epidural blood patch was performed that successfully relieved her symptom. Stronger progressive headache with nausea reappeared two days later and the parturient was readmitted to hospital. Urgent neuroimaging examinations detected CVT of right the transverse sinus, ipsilateral cortical veins, and partially occluded superior sagittal sinus, as well as bilateral subacute/chronic SDHs. The treatment of the patient with low molecular weight heparin and antiaggregation therapy was effective. In this case, the diagnosis was delayed because of atypical clinical presentation and potentially confounding events (epidural analgesia and assumption that it was a case of PDPH). It is important to carefully observe patients in such conditions and promptly conduct suitable diagnostic tests. Otherwise, unrecognized intracranial complications and delay of appropriate therapy could be life-threatening.
Belavic´ M, Sotošek Tokmadžić V, Brozović Krijan A, et al.Ther Clin Risk Manag. 2018;14:741-751.In this article, the author Josip Žunic´ did not meet the criteria for authorship and was erroneously ...included in the authors list. The authors wish to apologize for this error.Read the original article.
The aim of this study was to determine the prevalence of true local anesthetic (LA) allergy among patients referred for suspected hypersensitivity and to describe the main characteristics of adverse ...drug reactions (ADR) induced by LA in our population. We retrospectively analyzed the medical files of patients referred to the Department of Dermatovenereology, University Hospital Center Rijeka, Rijeka, Croatia, for the investigation of LA hypersensitivity in the period between January 2000 and December 2012. A total of 331 patients underwent skin testing and, in cases of negative results, subcutaneous exposition to LA. In patients with suspected delayed reaction, patch test was performed. Altogether, 331 patients reported 419 independent ADR occurring during 346 procedures. Most commonly, patients reported having only one ADR, but 41 (12.4%) of them had two reactions, 14 (4.2%) had three, five (1.5%) had four and in one patient (0.3%) five ADR to LA were observed. The majority of reactions occurred during dental procedures when most commonly lidocaine and articaine were used. Local reactions were reported in 44 patients, whereas 490 general symptoms occurred during 375 independent ADR in 287 patients. The most common symptoms were cardiovascular system reactions in 89 patients (18.2%). Allergic reaction was detected in three patients (0.91%). One patient showed immediate‐type reaction to bupivacaine and two patients had a delayed‐type reaction to lidocaine. Adverse reactions to LA are common and are mostly due to their pharmacological properties and drug combinations or psychogenic origin. Allergic accidents to LA are rare.
Preoperative management involves patients fasting from midnight on the evening prior to surgery. Fasting period is often long enough to change the metabolic condition of the patient which increases ...perioperative stress response. That could have a detrimental effect on clinical outcome. The aim of the present study was to investigate the possible effects of carbohydrate-rich beverage on stress response after colon resection.
Randomized and double blinded study included 40 patients with colon, upper rectal or rectosigmoid cancer. Investigated group received a carbohydrate-rich beverage the day before and two hours before surgery. In the control group patients were in the standard preoperative regime: nothing by mouth from the evening prior to operation. Peripheral blood was sampled 24h before surgery, at the day of the surgery, and 6, 24 and 48h postoperatively.
Colonic resection in both groups caused a significant increase in serum interleukin 6 (IL-6) levels 6, 24 and 48h after the operation. Increase was more evident and statistically significant in the group with fasting protocol. More significant increase of interleukin 10 (IL-10) occurred in patients who received preoperative nutrition.
Smaller increase in IL-6 and higher in IL- 10 are indicators of reduced perioperative stress.
Pylorus-preserving pancreaticoduodenectomy (PPPD) is the standard treatment for periampullary and pancreatic head tumors. Delayed gastric emptying (DGE) is the most common (ranging from 15-45%) but ...not life threatening complication and impairs patient recovery and prolongs the hospital stay after PPPD. The precise pathomechanism of DGE is still unclear. The aim of this study was to evaluate whether the method of pyloric dilatation performed at the time of PPPD could improve gastric emptying.
Forty patients underwent PPPD for pancreatic or periampullary lesions from January 1999 to July 2004 were included in this study. In twenty patients mechanical dilatation of the pylorus after duodenal transaction was performed (PPPD+PD group) while in other twenty PPPD was not followed with pyloric dilatation (PPPD group). The incidence of DGE as well as other complications was analyzed. Delayed gastric emptying was defined as gastric stasis requiring nasogastric intubation for more than 4 postoperative days (POD), or the inability to tolerate a regular diet on the 8th POD.
Delayed gastric emptying occurred in seven (35%) out of the 20 patients in the PPPD group, while none of the 20 patients in the PPPD+PD group developed DGE.
Pyloric dilatation reduces DGE after PPPD enabling patients to return sooner to a normal diet.
The type of pain after laparoscopic surgery differs considerably from that seen after laparotomy. Whereas laparotomy results mostly in parietal pain, patients after laparoscopic cholecystectomy ...complain more of visceral pain results from the stretching of intraabdominal cavity, peritoneal inflammation and phrenic nerve irritation caused by residual carbon dioxide in the peritoneal cavity. Intraperitoneal (IP) administration of some drugs can be effective for pain relief after laparoscopic surgery. The purpose of this study was to asses the effects of intraperitoneal application of bupivacaine or bupivacaine in combination with tramadol on pain relief after laparoscopic cholecystectomy. After informed written consent and local ethic committee approval, ninthy patients of ASA I and II grade undergoing elective laparoscopic cholecystectomy for cholelythiasis were recruited in the study. At the end of laparoscopic cholecystectomy 30 patients in each group received 50 mL saline 0.9% (group C), bupivacaine 0.25% (group B) or bupivacaine 0.25% with tramadol 100 mg (group T). VAS pain was estimated at 30 minutes, 1, 2, 4 and 24 hours after surgery. Postoperative analgesic requires were also assessed. Pain scores were significantly lower in group receiving the IP bupivacaine with tramadol and bupivacaine compared to saline group. Intraperitoneal applications of these drugs reduced consumption of supplementary postoperative analgesic medication. Intraperitoneal administration of bupivacaine with tramadol and bupivacaine are simple to use and effective in a reduction ofpain after laparoscopic cholecystectomy. In our study we found no differences between bupivacaine with tramadol and bupivacaine in postoperative VAS score and analgesic requirements.
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