Hyperbaric oxygen therapy for treatment of a late presenting ischaemic complication from hyaluronic acid cosmetic filler injection.

Vascular compromise and resulting ischaemic injury are known rare complications of cosmetic filler injections. Most hyaluronic acid vascular compromises present early and can be treated effectively by hyaluronidase. Here we present a case of ischaemic wound and mucosal necrosis after cosmetic facial hyaluronic acid injection that appeared within hours of injection but was not diagnosed and treated for 5 days. At day 5, the patient was treated with hyaluronidase injection immediately followed by 14 sessions of daily hyperbaric oxygen therapy (HBOT). Despite the delayed treatment, the patient had essentially complete recovery and the hyperbaric therapy was overall well-tolerated. Our case report suggests that hyaluronidase injection with concurrent daily HBOT sessions may be effective to allow recovery from late-presenting filler ischaemic complication. Furthermore, given the safety profile of HBOT, we suggest a more deliberate approach to this modality as a therapeutic adjunct by cosmetic practitioners when similar complications arise.

PORIMIN: The key to (+)-Usnic acid-induced liver toxicity and oncotic cell death in normal human L02 liver cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Usnic acid (UA) is one of the well-known lichen metabolites that induces liver injury. It is mainly extracted from Usnea longissima and U. diffracta in China or from other lichens in other countries. U. longissima has been used as traditional Chinese medicine for treatment of cough, pain, indigestion, wound healing and infection. More than 20 incidences with hepatitis and liver failure have been reported by the US Food and Drug Administration since 2000. UA is an uncoupler of oxidative phosphorylation causing glutathione and ATP depletion. Previous histological studies observed extensive cell and organelle swellings accompanied with hydrotropic vacuolization of hepatocytes. AIM OF THE STUDY: This study was to investigate the mechanism of UA-induced liver toxicity in normal human L02 liver cells and ICR mice using various techniques, such as immunoblotting and siRNA transfection. MATERIALS AND METHODS: Assays were performed to evaluate the oxidative stress and levels of GSH, MDA and SOD. Double flouresencence staining was used for the detection of apoptotic cell death. The protein expressions, such as glutathione S transferase, glutathione reductase, glutathione peroxidase 4, catalase, c-Jun N-terminal protein kinase, caspases, gastamin-D and porimin were detected by Western blotting. Comparisons between transfected and non-transfected cells were applied for the elucidation of the role of porimin in UA-induced hepatotoxicity. Histopathological examination of mice liver tissue, serum total bilirubin and hepatic enzymes of alanine aminotransferase and aspatate aminotransferase were also studied. RESULTS: The protein expressions of glutathione reductase, glutathione S transferase and glutathione peroxidase-4 were increased significantly in normal human L02 liver cells. Catalase expression was diminished in dose-dependent manner. Moreover, (+)-UA did not induce the activation of caspase-3, caspase-1 or gasdermin-D. No evidence showed the occurrence of pyroptosis. However, the porimin expressions were increased significantly. In addition, (+)-UA caused no cytotoxicity in the porimin silencing L02 cells. CONCLUSIONS: In conclusion, (+)-UA induces oncotic L02 cell death via increasing protein porimin and the formation of irreversible membrane pores. This may be the potential research area for future investigation in different aspects especially bioactivity and toxicology.

Ischemic and Thrombotic Events Associated with Concomitant Xa-inhibiting Direct Oral Anticoagulants and Antiepileptic Drugs: Analysis of the FDA Adverse Event Reporting System (FAERS).

INTRODUCTION: Factor Xa-inhibiting direct oral anticoagulants (FXa-DOACs) undergo hepatic metabolism via cytochrome P-450 (CYP450). Concomitant use of rifampicin, an inducer of these enzymes, with FXa-DOACs, has been shown to decrease FXa-DOAC concentrations in healthy subjects. Several common antiepileptic drugs (AEDs) are known to induce CYP450 enzymes as well. However, little is known regarding the impact of this potential interaction on treatment outcomes with FXa-DOACs. METHODS: We analyzed adverse event cases submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from January 2013 to December 2018. We compared the proportion of cases reporting thromboembolic and ischemic adverse events (TAIAEs) with the concomitant use of FXa-DOACs and enzyme-inducing AEDs to the proportion of cases with FXa-DOACs and other AEDs. RESULTS: During this period, 9693 adverse event cases reported concomitant use of FXa-DOACs and AEDs. Almost all reports (> 99%) involved the use of rivaroxaban or apixaban. Compared with other AEDs, enzyme-inducing AEDs were associated with an 86% increase in the odds of reporting TAIAEs [reporting odds ratio (ROR) 1.86, 95% confidence interval (CI) 1.61-2.15; p < 0.0001]. In secondary separate analyses of rivaroxaban and apixaban, enzyme-inducing AEDs were similarly associated with increased reporting of a TAIAE (ROR 1.79, 95% CI 1.50-2.12, and ROR 1.88, 95% CI 1.41-2.48, respectively). CONCLUSION: Using real world data, we observed an increase in the odds of reporting anticoagulation treatment failure among patients treated with FXa-DOACs and concomitant enzyme-inducing AEDs compared to those treated with other AEDs.

The effect of TENS on random pattern flap survival in nicotinized rats.

The adverse effects of cigarettes, due to their nicotine content, may cause important ischemic complications in flaps. Electrical stimulation increases blood flow in ischemic tissues, the level of vascular endothelial growth factor, capillary density, and angiogenesis while decreasing oxygen tension in tissues. Electrical stimulation is also known to increase survival rate in flaps. In this study, which tests the hypothesis that TENS (a type of electrical stimulation) contributes to enhancement of flap viability by eliminating the adverse effects of nicotine, 40 rats were divided into 4 groups of 10 rats. Nicotinization was achieved by subcutaneous administration of 2 mg/kg per day to the rats, other than those in the Control group, for 4 weeks. The rats in one of the nicotinized groups received 20 mA, 80 Hz TENS (TENS1 group) for 1 hour daily throughout the last week before McFarlane flaps of random pattern were made in the backs of all the rats. Another nicotinized group was subjected to TENS in a similar dose after flap elevation (TENS2 group). Flap blood flow was measured before and 48 hours after their construction, and their fluorescein perfusion was measured immediately after the flap elevation. The comparison of the survival rates of the flaps revealed that, although the blood flow in the Nicotine group was significantly lower than in the Control group, it was significantly higher in the TENS1 group than in both the Control and Nicotine groups. The proportion of the area stained with fluorescein, immediately after the elevation of flaps, was significantly reduced in the Nicotine group compared to the Control group. In the TENS1 group, however, it was greater than in the nicotine and TENS2 groups. Flap viability rates decreased significantly in the Nicotine group compared with the Control group. In the TENS2 group, however, an increase was observed compared with the Nicotine group.These findings suggest that although TENS performed before flap elevation does not contribute to flap survival, despite causing a rise in blood flow, it enhances flap survival when applied postoperatively. Given the practicality and low cost of TENS, it can be concluded that it may be possible to use it in the management of ischemic complications in flap operations in smokers.

Successful treatment with enoxaparin of glans ischemia due to local anesthesia after circumcision.

The severe ischemia or necrosis of the glans penis is a rarely seen complication after circumcision. We report the case of a 7-year-old boy with severe glans penis ischemia occurring 24 hours after circumcision with local anesthesia (0.1% xylocaine containing ephedrine). His hemogram and levels of proteins C and S and fibrinogen were normal, but the D-dimer level was higher than normal (2.57 mg/L; normal level 0-0.5 mg/L). Normal blood flow was indicated on color Doppler ultrasonography. The severe ischemia in the glans penis was successfully treated with subcutaneous injection of enoxaparin (low-molecular-weight heparin) for 5 days, and the appearance of the glans was close to normal on the fifth day. The patient did not require any surgical intervention and was discharged without sequelae. As a result, we consider that ischemia of the glans penis may initially be managed with enoxaparin, especially in cases in which the D-dimer level is higher than normal.

Acute hand ischemia after intra-arterial injection of meprobamate powder.

BACKGROUND: Meprobamate tablets contain microcrystalline cellulose, a potent embolic agent that has been shown to cause gangrene in animal studies. Microvascular embolization caused by microcrystalline cellulose can contribute to the ischemic process. OBJECTIVE: We report a case of acute hand ischemia after accidental intra-arterial injection of crushed meprobamate powder in a 23-year-old male drug abuser. CASE REPORT: The distal tips of the patient's right thumb, index finger, ring finger, and little finger continued to develop gangrene despite medical therapy with heparinization, low molecular-weight dextran infusion, corticosteroid administration, and hyperbaric oxygen therapy. CONCLUSION: We believe this is the first case of acute limb ischemia caused by intra-arterial injection of meprobamate powder documented in humans. Emergency physicians should be aware that accidental intra-arterial injection of crushed oral drug formulations is potentially limb threatening and prompt recognition of similar clinical scenarios is of vital importance.

Intestinal Necrosis Associated with Orally Administered Calcium Polystyrene Sulfonate Without Sorbitol.

OBJECTIVE: To describe a case of extensive intestinal necrosis with oral intake of calcium polystyrene sulfonate without sorbitol. CASE SUMMARY: A 73-year-old woman was admitted to the emergency department with abdominal pain. Abdominal computed tomography (CT) scan showed widespread dilatation of the bowel. The diagnosis of acute colonic pseudoobstruction was made. On day 3, her serum potassium level rose to 5.6 mEq/L. It was treated with hydrocortisone 100 mg/day and calcium polystyrene sulfonate 15 g/day via nasogastric tube from day 3 to day 6. On day 6, the severe abdominal pain recurred, with abdominal tenderness. CT scan showed pneumoperitoneum and peritoneal effusion. At surgery, 2 lenticular jejunal perforations and an ischemic cecum were found. Microscopic findings indicated that the transmural abscess contained massive inflammatory infiltrate and the cecal mucosa showed ulceration and inflammation with a fibrinous and purulent coating. Small gray-purple or blue angulated crystals were embedded in the cecal and most of the jejunal mucosal ulcers. On day 19, the patient died of multiple organ failure after her third laparotomy. DISCUSSION: Ion-exchanging resins are given orally or by retention enema for the treatment of hyperkalemia. The most commonly used and best-established resin is sodium polystyrene sulfonate. However, it is known to promote colonic necrosis when sorbitol is also given or especially in patients with renal failure or postoperative ileus. Calcium polystyrene sulfonate is another ion-exchange resin. There are few reports of adverse effects in the literature. Our case is interesting for 2 reasons: the resin given was calcium polystyrene sulfonate and sorbitol was not used. CONCLUSIONS: Like sodium polystyrene sulfonate, calcium polystyrene sulfonate is an ion-exchanging resin that can promote bowel necrosis. We believe that it should not be used with sorbitol or when bowel transit time is slowed.

Amaurosis, ophthalmoplegia, ptosis, mydriasis and periorbital blanching following inferior alveolar nerve anaesthesia.

BACKGROUND: Ophthalmic complications following inferior alveolar nerve anaesthesia are rare. They include transient blindness (amaurosis), ophthalmoplegia, ptosis, mydriasis and diplopia. These events may occur following the intravascular administration of anaesthetic solution and are distressing to both patient and operator alike. CASE REPORT: We report the unusual case of a young patient who experienced amaurosis, total ophthalmoplegia, complete upper eyelid ptosis, mydriasis and periorbital blanching following inferior alveolar nerve anaesthesia. Similar but less profound signs were observed in the same patient on a subsequent occasion. This was following general anaesthesia, during which she had received local anaesthetic prior to mandibular wisdom tooth removal. CONCLUSIONS: Ophthalmic complications following inferior alveolar nerve anaesthesia are rare but distressing events. In particular, amaurosis is an extremely rare event and usually heralds a more sinister pathology such as stroke. Clinicians should be aware of these complications to minimise anxiety and reassure their patients appropriately.

Colon perforation during sorafenib therapy for advanced hepatocelluar carcinoma. A case report.

There are no effective conventional systemic cytotoxic therapies for patients with unresectable or advanced hepatocellar carcinoma (HCC). Sorafenib, an oral multi-targeted tyrosine kinase inhibitor, was recently approved for the treatment of patients with HCC. Sorafenib is generally well tolerated and has an acceptable toxicity profile.Gastrointestinal perforation is a rare adverse event. We present a case of transverse colon perforation during sorafenib therapy for advanced HCC. A 68-year-old woman with advanced HCC was treated with sorafenib. Eight weeks later the patient presented with the sudden onset of sharp abdominal pain. Emergency surgery was performed for panperitonitis and a perforation involving the transverse colon.

Vasopressin in sepsis and septic shock.

Arginine vasopressin (AVP) and its synthetic, long-acting analog terlipressin (TP) are potent alternative vasoconstrictors in the treatment of septic patients with catecholamine-refractive vasodilatatory shock. The results from one large randomized clinical trial suggest that AVP plus norepinephrine (NE) infusion is as safe and effective as treatment with NE alone in patients with septic shock. Because the desired effects of vasopressin analogs are basically related to their vasopressinergic effects via the V1a receptor, more selective V1 agonists, such as TP, may be more potent in reversing sepsis-related arterial hypotension. In this regard, recent evidence from small-scale studies suggests that continuous low-dose infusion rather than intermittent bolus injection of TP is associated with fewer side effects, such as depression of cardiac output and rebound arterial hypotension. However, because clinical data on the administration of TP in patients with sepsis are limited, it should not currently be used beyond the scope of controlled trials. The optimal time point for the initiation of therapy with vasopressin analogs has yet to be determined. While AVP and TP are commonly used as last-resort therapies in severe septic shock, some evidence supports the initiation of treatment in a less severe state of the disease.

Aortobifemoral embolism in an 18-year old patient following cisplatin and 5-fluorouracil chemotherapy for nasopharyngeal carcinoma.

After cisplatin / 5-fluorouracil chemotherapy for nasopharyngeal carcinoma, an 18-year female patient developed aortobifemoral embolism. Besides chemotherapy, additional risk factors for arterial thromboembolic events were smoking, contraceptive medication and adjuvant antiemetic treatment with dexamethasone. Thrombophilia screening was negative. Thromboembolic complications during or after cisplatin have been reported in a frequency of 17.6 % in lung cancer patients, and in 8.4 % of patients with germ cell tumors. The incidence of arterial thromboembolic events was 9.3 % and 1.7 %, respectively. The pathogenesis of cisplatin induced thromboembolism is thought to be caused by endothelial damage leading to endothelial cell dysfunction, increased von Willebrand factor plasma levels, and hypomagnesaemia.

Tobacco smoking and surgical healing of oral tissues: a review.

It is believed that the crew of Columbus had introduced tobacco from the 'American India' to the rest of the world, and tobacco was attributed as a medicinal plant. It was often used to avert hunger during long hours of work. But in reality, tobacco causes various ill effects including pre-malignant lesions and cancers. This article aims at reviewing the literature pertaining to the effect of tobacco smoking upon the outcome of various surgical procedures performed in the oral cavity. Tobacco affects postoperative wound healing following surgical and nonsurgical tooth extractions, routine maxillofacial surgeries, implants, and periodontal therapies. In an experimental study, bone regeneration after distraction osteogenesis was found to be negatively affected by smoking. Thus, tobacco, a peripheral vasoconstrictor, along with its products like nicotine increases platelet adhesiveness, raises the risk of microvascular occlusion, and causes tissue ischemia. Smoking tobacco is also associated with catecholamines release resulting in vasoconstriction and decreased tissue perfusion. Smoking is believed to suppress the innate and host immune responses, affecting the function of neutrophils--the prime line of defense against infection. Thus, the association between smoking and delayed healing of oral tissues following surgeries is evident. Dental surgeons should stress on the ill effects of tobacco upon the routine postoperative healing to smoker patients and should aid them to become tobacco-free.

[Ischemic anastomotic bowel perforation during treatment with bevacizumab 10 months after surgery]. / Ischämische Anastomosenperforation im Bereich einer Ileotransversostomie unter Therapie mit Bevacizumab.

BACKGROUND: Bevacizumab (Avastin) is a monoclonal antibody against vascular endothelial growth factor (VEGF) receptor that has demonstrated increased overall survival when added to standard chemotherapy regimens in patients with metastatic colorectal cancer. Gastrointestinal perforation is a known risk factor of unknown etiology associated with the use of bevacizumab. OBJECTIVE: We report a 61-year-old woman with adenocarcinoma of the colon ascendens who underwent hemicolectomy and adjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin. Eight months after the operation, we started therapy with bevacizumab combined with irinotecan, 5-fluorouracil, and leucovorin due to disease progression. Two months after completion of this therapy, ischemic anastomotic bowel perforation occurred and a resection of the anastomosis was performed. Because of anastomotic insufficiency 8 days later, a further revision had to be done and the terminal ileum and the colon were brought out through a stoma. DISCUSSION: This case is unusual because the time interval between the primary operation and the application of bevacizumab is regarded as safe with regard to the risk of perforation. An ischemic genesis of the perforation was considered on the basis of the histopathological workup. In case of perforations during therapy with bevacizumab, a safe surgical approach should be preferred, i.e., a transient stoma instead of a primary reconstruction of the bowel passage.

Dimethyl sulfoxide as a block to the deleterious effect of nicotine in a random skin flap in the rat.

BACKGROUND: In plastic surgery, a causal relationship between heavy smoking and flap necrosis has been shown. The deleterious effect of nicotine in random skin flaps in rats has also been proven, being related to vasoconstriction and possibly reactive oxygen species. This study aimed to verify the capacity of dimethyl sulfoxide, an antioxidant, to block the deleterious effect of nicotine in a random skin flap. METHODS: Fourteen adult male Wistar-EPM rats were distributed at random into two groups of seven animals. The nicotine group received this drug subcutaneously (1.2 mg/kg/day), for 1 week before flap elevation. The nicotine plus dimethyl sulfoxide group followed the same routine. Five minutes before the surgical procedure, rats in the nicotine group received distilled water orally and rats in the nicotine plus dimethyl sulfoxide group received dimethyl sulfoxide orally (2 ml/kg). Blood and skin tissue samples were collected to allow determination of malondialdehyde levels. RESULTS: The nicotine group had a mean value of 40.2 percent and the nicotine plus dimethyl sulfoxide group had a mean value of 20.6 percent necrosis (p = 0.009). Malondialdehyde levels in both serum and skin samples were lower in the animals that received dimethyl sulfoxide. CONCLUSION: The deleterious effect of nicotine was effectively blocked by dimethyl sulfoxide.

[Pepper spray injuries of the anterior segment of the eye]. / Pfeffersprayverletzungen des vorderen Augensegmentes.

BACKGROUND: A wide variety of pepper sprays is currently available and gaining increasing popularity among both professional guardians and amateurs. Adverse side effects to the anterior segment of the eye are known but underestimated. HISTORY AND SIGNS: We present two cases with severe corneal and conjunctival damage after accidental self injury by a pepper spray (Jet Protector Guardian Angel), benzyl alcohol 90.1 %, capsaicinoids 2.6 %). THERAPY AND OUTCOME: Despite immediate and intensive irrigation, a complete epithelial defect, extensive ischemia to the limbus and the conjunctiva and a circular conjunctival chemosis were diagnosed. After slow re-epithelialization in both cases, a neurotrophic superficial keratitis, a reduced corneal sensibility and in one case deep stromal scarring were noted. CONCLUSIONS: Pepper spray application to the eye might result in severe and permanent damage to the corneo-conjunctival tissue which is not adequately addressed in the current literature. From the present case reports arise the discussion whether the irritative and lipophilic capsacin/benzyl alcohol mixture or the pyrotechnical additives nitrocellulose und sinoxide are responsible for the anterior segment injuries.

Calcium antagonists in N-methyl d-aspartate-induced retinal injury.

PURPOSE: To detect the neuroprotective role of nimodipine and dantrolene in N-methyl- d-aspartate (NMDA)-induced retinal injury. METHODS: In this study we used two calcium antagonists which have two different modes of action, nimodipine and dantrolene, to prevent NMDA-induced retinal ischemia in guinea pigs. In 40 animals we injected nimodipine (n=10), dantrolene (n=10), a combination of both (n=10) or sterile 0.9% NaCl solution as a placebo (n=10) before intravitreal injection of NMDA. We enucleated one eye of each animal after 48 hours and performed histopathologic examination. We also measured malondialdehyde (MDA) levels in retinal homogenates as a marker of ischemic injury. RESULTS: Our results indicate that ganglion cells of the retina were preserved mostly by nimodipine, followed by combined nimodipine-dantrolene, and dantrolene respectively. The ganglion cell count was statistically significantly higher in cases where we used calcium antagonists than in the control group (p<0.05). We also found that MDA was significantly reduced by calcium antagonists compared to the control group (p<0.05). CONCLUSION: Our data show that nimodipine and dantrolene both have potential neuroprotective effects; nimodipine preserved retinal ganglion cells to a greater extent than dantrolene from NMDA-induced retinal injury.