It is Time to Replace Large Drains with Small Ones After Fixation of Rib Fractures: A Prospective Observational Study.

INTRODUCTION: Large-bore chest tubes are usually applied after thoracic surgery. Recently, small-bore tubes have been increasingly considered owing to the extensive use of video-assisted thoracoscopic surgery (VATS). This study assessed the differences in outcomes between large-bore and small-caliber drainage tubes in patients undergoing surgical stabilization of rib fractures (SSRF) with VATS. METHODS: Overall, 131 patients undergoing SSRF with VATS were prospectively enrolled, including 65 patients receiving 32-Fr chest tubes (group 1) and 66 patients receiving 14-Fr pigtail catheters (group 2) for postoperative drainage. The clinical characteristics and perioperative outcomes of the patients were compared. RESULTS: All patients underwent SSRF with VATS within 4 days after trauma. After the operation, the mean duration of chest tubes was longer than that of pigtail catheters, with statistical significance (5.08 ± 2.47 vs 3.11 ± 1.31, P = 0.001). Length of stay (LOS) was also longer in group 1 (10.38 ± 2.90 vs 8.18 ± 2.44, P = 0.001). After multivariate logistic regression, the only independent factors between the two groups were duration of postoperative drainage (adjusted odds ratio [AOR] 1.746; 95% confidence interval [CI] 0.171-10.583, P = 0.001) and hospital LOS (AOR 1.272; 95% CI 0.109-4.888, P = 0.027). CONCLUSION: After reconstruction of the chest wall and lung parenchyma, small-caliber drainage catheters could be easily and safely applied to reduce hospital LOS.

Morphine produces better thermal analgesia in young Huntington mice and are associated with less neuroinflammation in spinal cord.

BACKGROUND: Huntington's disease (HD) is an inherited disease characterized by both mental and motor dysfunctions. Our previous studies showed that HD mice demonstrate a diminished pain response. However, few studies have focused on the relationship between HD and morphine analgesia. The purpose of this study is to investigate and compare the analgesic effects of morphine in HD and wild-type (WT) mice. METHODS: We used clinically similar transgenic HD mice (7-10 weeks of age with motor dysfunction at 8-9 mo of age) carrying a mutant Huntington CAG trinucleotide repeats to evaluate morphine analgesia. The morphine (10 mg/kg subcutaneously) analgesia was evaluated with a tail-flick in hot water (52°C). Mice spinal cords were harvested at the end of the analgesia studies. An immunofluorescence assay and western blotting were used to identify changes in the cells and cytokines. RESULTS: Our data demonstrate that preonset young HD mice exhibited a better analgesic response to morphine than the WT mice. Western blotting and an immunohistological examination of the lumbar spinal cord tissue indicated less activation of glial cells and astrocytes in the HD mice compared with the WT mice. The production levels of tumor necrosis factor α and interleukine-1ß were also lower in the young HD mice. CONCLUSION: Our data demonstrate better morphine analgesic and less pain-related cytokine responses at the spinal cord level for HD mice. Further studies are needed to determine the morphine analgesia mechanism in HD.

The analgesic effect of propofol associated with the inhibition of hypoxia inducible factor and inflammasome in complex regional pain syndrome.

BACKGROUND: Complex regional pain syndrome (CRPS) is related to microcirculation impairment caused by tissue hypoxia and peripheral cytokine overproduction in the affected human limb and chronic post-ischemic pain (CPIP) is considered as an animal model for this intractable disease. Previous studies suggest that the pathogenesis of CPIP involves the hypoxia inducible factor-1α (HIF-1α) and an exaggerated regional inflammatory and free radical response. The inhibition of HIF-1α is known to relieve CPIP. So, propofol, as a free radical scavenger, is very likely to be beneficial in terms of relieving CPIP. METHODS: We set up a CPIP model using the hindpaw of mice. We administered propofol (10 mg/kg) just after the reperfusion period (early stage) and also on the second day (late stage), as treatment. The analysis evaluated the expression of HIF-1α, free radicals, and inflammasome. RESULTS: Propofol administration produced obvious analgesia in both mechanical and thermal evaluation in the early stage of CPIP (2 h after reperfusion). Only a mild analgesic effect was found in the late stage (48 h later after reperfusion). In the early stage, the expression of HIF-1α and the inflammasome marker (NALP1) along with caspase-1 were suppressed by propofol. The free radical level also decreased in the propofol group. But those molecular changes were not founded in the late stage of CPIP. CONCLUSION: Our data demonstrated that propofol produces mice analgesia in the early stage of CPIP and this effect is associated with inhibition of free radical, hypoxia inducible factor and inflammasome.

Effectiveness of nalbuphine, a κ-opioid receptor agonist and µ-opioid receptor antagonist, in the inhibition of INa , IK(M) , and IK(erg) unlinked to interaction with opioid receptors.

Nalbuphine (NAL) is recognized as a mixer with the κ-opioid receptor agonist and the µ-opioid receptor antagonist. However, whether this drug causes any modifications in neuronal ionic currents is unclear. The effects of NAL on ionic currents in mHippoE-14 hippocampal neurons were investigated. In the whole-cell current recordings, NAL suppressed the peak amplitude of voltage-gated Na+ current (INa ) with an IC50 value of 1.9 µM. It shifted the steady-state inactivation curve of peak INa to the hyperpolarized potential, suggesting that there is the voltage dependence of NAL-mediated inhibition of peak INa . In continued presence of NAL, subsequent application of either dynorphin A1-13 (1 µM) or naloxone (30 µM) failed to modify its suppression of peak INa . Tefluthrin (Tef; 10 µM), a pyrethroid known to activate INa , increased peak INa with slowed current inactivation; however, further application of NAL suppressed Tef-mediated suppression of peak INa followed by an additional slowing of current inactivation. In addition, NAL suppressed the amplitude of M-type K+ current [IK(M) ] with an IC50 value of 5.7 µM, while it slightly suppressed erg-mediated and delayed-rectifier K+ currents. In the inside-out current recordings, NAL failed to modify the activity of large-conductance Ca2+ -activated K+ channels. In differentiated NG108-15 neuronal cells, NAL also suppressed the peak INa , and subsequent addition of Tef reversed NAL-induced suppression of INa . Our study highlights the evidence that in addition to modulate opioid receptors, NAL has the propensity to interfere with ionic currents including INa and IK(M) , thereby influencing the functional activities of central neurons.

Rib soft fixation produces better analgesic effects and is associated with cytokine changes within the spinal cord in a rat rib fracture model.

Traumatic rib fracture can cause severe pain and is usually associated with the depression of respiratory drive followed by severe respiratory complications. It is critical for patients with rib fracture to receive adequate analgesia. However, strong opioids and other analgesics often produces side effects and may even cause respiratory suppression. Meanwhile, rib fixation now has become a popular method for treating rib fracture patients. However, the actual molecular mechanism leading to its effectiveness as an analgesia has not been fully investigated, and the best analgesic method for its use in rib fracture patients has not yet been determined. We developed a new animal model for rib fracture and evaluated changes in pain severity after rib fixation. Our data indicated significantly better analgesic behavior if a soft string rib fixation is performed, which is associated with cytokine (interleukine-6 and interleukine-10) decreases in the spinal cord and co-localization with glia cells. Our results provided a treatment suggestion for rib fracture patients and the possible molecular mechanism for the analgesic effects. Further molecular mechanisms and the best therapeutic methods are still needed for this severe painful condition.

Incarcerated Hiatal Hernia with Perforation after Laparoscopic Total Gastrectomy with Roux-en-Y Reconstruction: a Case Report.

The occurrence of hiatal hernia after total gastrectomy with Roux-en-Y reconstruction is rare. We report the case of a 76-year-old man who presented with dyspnea, vomiting, and fever around 8 days after total gastrectomy with Roux-en-Y reconstruction. Abdominal computed tomography revealed a hiatal hernia containing part of the small intestine in the left thoracic cavity. Emergent reduction and repair of the hiatal hernia were performed later. Operative findings revealed that the Roux limb was incarcerated in the left pleural cavity. Esophagojejunostomy leakage, perforation of the small intestine with transient ischemic change, and pyothorax were also found. Thus, feeding jejunostomy, thoracoscopic decortication, and diversion T-tube esophagostomy were performed. Considering that the main cause of hiatal hernia is blunt dissection with division of the phrenoesophageal membrane, approximating the crus with 1 or 2 figure-8 sutures, according to the size of the defect, to prevent the incidence of hiatal hernia after total gastrectomy may be performed.

Parecoxib, a selective blocker of cyclooxygenase-2, directly inhibits neuronal delayed-rectifier K+ current, M-type K+ current and Na+ current.

Parecoxib, a prodrug of valdecoxib, is a selective inhibitor of cyclooxygenase-2 and widely used for traumatic and postoperative patients to avoid opioid-induced side effects. It is a potent analgesic and has a role in multimodal analgesic and enhanced recovery after surgery. Whether parecoxib exerts any actions on these types of ionic currents remains unclear. In this study, we investigated whether it exerts any effects on ion currents in differentiated NG108-15 neuronal cells. Cell exposure to parecoxib (1-30 µM) caused a reversible reduction in the amplitude of IK(DR) with an IC50 value of 9.7 µM. The time course for the IK(DR) inactivation in response to a long-lasting pulse was changed to the biexponential process during cell exposure to 3 µM parecoxib. Other agents known to inhibit the cyclooxygenase activity have minimal effects on IK(DR). Parecoxib enhanced the degree of excessive accumulative inhibition of IK(DR) inactivation evoked by a train of brief repetitive stimuli. This compound suppressed the amplitude of M-type K+ current. It depressed the peak amplitude of voltage-gated Na+ current with no change in the current-voltage relationship of this current. However, it did not have any effect on hyperpolarization-activated cation current. No change in the expression level of KV3.1 mRNA was detected in the presence of parecoxib. The effects of parecoxib on ion currents are direct and unrelated to its inhibition of the enzymatic activity of cyclooxygenase-2. The inhibition of these ion channels by parecoxib may partly contribute to the underlying mechanisms by which it affects neuronal function in vivo.

Effect of Captopril on Ca²âº Homeostasis and Cell Viability in Human Hepatoma Cells.

Captopril, an angiotensin-converting enzyme (ACE) inhibitor, induced different Ca²âº signaling responses in various cell models. However, the effect of captopril on Ca²âº homeostasis and cell viability in hepatoma cells is unknown. This study examined whether captopril altered Ca²âº homeostasis and viability in HepG2 human hepatoma cells. Intracellular Ca²âº concentrations in suspended cells were monitored by using the fluorescent Ca²âº-sensitive dye fura-2. Cell viability was examined by using 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] water soluble tetrazolium-1 (WST-1). Captopril at concentrations of 500-3000 µM induced [Ca²âº]i rises in a concentration-dependent manner. Ca²âº removal reduced the signal by approximately 15%. Mn²âº has been shown to enter cells through similar mechanisms as Ca²âº but quenches fura-2 fluorescence at all excitation wavelengths. Captopril (3000 µM)-induced Mn²âº influx indirectly suggested that captopril evoked Ca²âº entry. Captopril-induced Ca²âº entry was inhibited by 15% by a protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate, PMA) and an inhibitor (GF109203X) and three inhibitors of store-operated Ca²âº channels: nifedipine, econazole and SKF96365. In Ca²âº-free medium, treatment with the endoplasmic reticulum Ca²âº pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished captopril-evoked [Ca²âº]i rises. Conversely, treatment with captopril abolished BHQ-evoked [Ca²âº]i rises. Inhibition of phospholipase C (PLC) with U73122 inhibited 70% of captopril-induced [Ca²âº]i rises. Captopril at concentrations between 150-550 µM killed cells in a concentration-dependent fashion. Chelation of cytosolic Ca²âº with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM) did not reverse captopril's cytotoxicity. Together, in HepG2 human hepatoma cells, captopril induced [Ca²âº]i rises and caused cell death that was not triggered by preceding [Ca²âº]i rises.

Early Management of Retained Hemothorax in Blunt Head and Chest Trauma.

BACKGROUND: Major blunt chest injury usually leads to the development of retained hemothorax and pneumothorax, and needs further intervention. However, since blunt chest injury may be combined with blunt head injury that typically requires patient observation for 3-4 days, other critical surgical interventions may be delayed. The purpose of this study is to analyze the outcomes of head injury patients who received early, versus delayed thoracic surgeries. MATERIALS AND METHODS: From May 2005 to February 2012, 61 patients with major blunt injuries to the chest and head were prospectively enrolled. These patients had an intracranial hemorrhage without indications of craniotomy. All the patients received video-assisted thoracoscopic surgery (VATS) due to retained hemothorax or pneumothorax. Patients were divided into two groups according to the time from trauma to operation, this being within 4 days for Group 1 and more than 4 days for Group 2. The clinical outcomes included hospital length of stay (LOS), intensive care unit (ICU) LOS, infection rates, and the time period of ventilator use and chest tube intubation. RESULT: All demographics, including age, gender, and trauma severity between the two groups showed no statistical differences. The average time from trauma to operation was 5.8 days. The ventilator usage period, the hospital and ICU length of stay were longer in Group 2 (6.77 vs. 18.55, p = 0.016; 20.63 vs. 35.13, p = 0.003; 8.97 vs. 17.65, p = 0.035). The rates of positive microbial cultures in pleural effusion collected during VATS were higher in Group 2 (6.7 vs. 29.0%, p = 0.043). The Glasgow Coma Scale score for all patients improved when patients were discharged (11.74 vs. 14.10, p < 0.05). DISCUSSION: In this study, early VATS could be performed safely in brain hemorrhage patients without indication of surgical decompression. The clinical outcomes were much better in patients receiving early intervention within 4 days after trauma.

The investigation of minoxidil-induced [Ca2+]i rises and non-Ca2+-triggered cell death in PC3 human prostate cancer cells.

Minoxidil is clinically used to prevent hair loss. However, its effect on Ca2+ homeostasis in prostate cancer cells is unclear. This study explored the effect of minoxidil on cytosolic-free Ca2+ levels ([Ca2+]i) and cell viability in PC3 human prostate cancer cells. Minoxidil at concentrations between 200 and 800 µM evoked [Ca2+]i rises in a concentration-dependent manner. This Ca2+ signal was inhibited by 60% by removal of extracellular Ca2+. Minoxidil-induced Ca2+ influx was confirmed by Mn2+-induced quench of fura-2 fluorescence. Pre-treatment with the protein kinase C (PKC) inhibitor GF109203X, PKC activator phorbol 12-myristate 13 acetate (PMA), nifedipine and SKF96365 inhibited minoxidil-induced Ca2+ signal in Ca2+ containing medium by 60%. Treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-ditert-butylhydroquinone (BHQ) in Ca2+-free medium abolished minoxidil-induced [Ca2+]i rises. Conversely, treatment with minoxidil abolished BHQ-induced [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 abolished minoxidil-evoked [Ca2+]i rises. Overnight treatment with minoxidil killed cells at concentrations of 200-600 µM in a concentration-dependent fashion. Chelation of cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM) did not prevent minoxidil's cytotoxicity. Together, in PC3 cells, minoxidil induced [Ca2+]i rises that involved Ca2+ entry through PKC-regulated store-operated Ca2+ channels and PLC-dependent Ca2+ release from the endoplasmic reticulum. Minoxidil-induced cytotoxicity in a Ca2+-independent manner.

The effect of oleuropein from olive leaf (Olea europaea) extract on Ca²âº homeostasis, cytotoxicity, cell cycle distribution and ROS signaling in HepG2 human hepatoma cells.

Oleuropein, a phenolic compound found in the olive leaf (Olea europaea), has been shown to have biological activities in different models. However, the effects of oleuropein on Ca(2+) homeostasis, cytotoxicity, cell cycle distribution and ROS signaling in liver cells have not been analyzed. Oleuropein induced [Ca(2+)]i rises only in HepG2 cells but not in AML12, HA22T or HA59T cells due to the different status of 3-hydroxy-3-methylglutaryl-CoA reductase expression. In HepG2 cells, this Ca(2+) signaling response was reduced by removing extracellular Ca(2+), and was inhibited by the store-operated Ca(2+) channel blockers 2-APB and SKF96365. In Ca(2+)-free medium, pretreatment with the ER Ca(2+) pump inhibitor thapsigargin abolished oleuropein-induced [Ca(2+)]i rises. Oleuropein induced cell cycle arrest which was associated with the regulation of p53, p21, CDK1 and cyclin B1 levels. Furthermore, oleuropein elevated intracellular ROS levels but reduced GSH levels. Treatment with the intracellular Ca(2+) chelator BAPTA-AM or the antioxidant NAC partially reversed oleuropein-induced cytotoxicity. Together, in HepG2 cells, oleuropein induced [Ca(2+)]i rises by releasing Ca(2+) from the ER and causing Ca(2+) influx through store-operated Ca(2+) channels. Moreover, oleuropein induced Ca(2+)-associated cytotoxicity that involved ROS signaling and cell cycle arrest. This compound may offer a potential therapy for treatment of human hepatoma.

The surgical stabilization of multiple rib fractures using titanium elastic nail in blunt chest trauma with acute respiratory failure.

BACKGROUND: Blunt chest injuries are usually combined with multiple rib fractures and severe lung contusions. This can occasionally induce acute respiratory failure and prolong ventilations. In order to reduce the periods of ventilator dependency, we propose a less invasive method of fixing multiple rib fractures. METHODS: Since October 2009, we have developed a new method to fix fractured ribs caused by blunt trauma. Rib fixations were performed using 2.0- or 2.5-mm intramedullary titanium elastic nails (TEN), with the help of video-assisted thoracoscopic surgery (VATS) and minimal thoracic incisions. All the patients' demographics and postoperative data were collected. RESULTS: From January 2010 to December 2012, a total of 65 patients presenting with multiple rib fractures resulting in acute respiratory failure were included in the study. Twelve patients received the new surgical fixation. Rib fixations were performed at an average of 4 days after trauma. Patients were successfully weaned off ventilators after an average of 3 days. The average length of stay in the hospital and the intensive care unit (ICU) was shorter for the patients with fixation than for nonsurgical patients. All twelve patients returned to normal daily activities and work. CONCLUSIONS: In the reconstruction of an injured chest wall, the VATS with TENs fixation in multiple rib fractures is feasible. This method is also effective in decreasing the length of the surgical wound. Because the structure of the chest cage is protected, the period of mechanical ventilation is shortened and the length of stay in the hospital and the ICU can be reduced.

Blunt abdominal injury with rupture of giant hepatic cavernous hemangioma and laceration of the spleen.

A 41-year-old woman with blunt abdominal trauma due to a motor vehicle accident presented to our emergency department. The patient had a history of a giant hepatic cavernous hemangioma. Emergency exploratory laparotomy was performed for suspected intra-abdominal bleeding with abdominal compartment syndrome, and more than 4 liters of blood and blood clots were removed. An active bleeding laceration (5 cm) of a hepatic cavernous hemangioma was detected in segment III of the liver. The bleeding was controlled by sutures, Teflon patches and tamponade. The abdomen was closed temporarily using the vacuum-assisted method. Because of the presence of persistent fresh blood through abdominal drainage at a rate of >1 L/h, splenectomy was performed to control the bleeding again by sutures and Teflon patches. Finally, the abdomen was closed using a biologic mesh. The patient was discharged home 30 days after trauma. Bleeding of trauma-caused hepatic hemangioma is rare, but splenic injury due to blunt abdominal trauma is common. An in-depth investigation is necessary to avoid second intervention.